PMID- 8460533 TI - Giant collagen plaques in Creutzfeld-Jakob disease. Report of two cases with ultrastructural studies. AB - We report two cases of Creutzfeld-Jakob disease with clusters of giant collagen fibers. To our knowledge, these abnormally large collagen fibers have never been described in patients with degenerative diseases of the central nervous system. The significance of the formation of such plaque-like large collagen fibers has as yet not been elucidated. It is felt that these represent a product of the degenerative process. PMID- 8460532 TI - Alzheimer neuropathology in mentally retarded adults: statistical independence of regional amyloid plaque and neurofibrillary tangle densities. AB - The densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed quantitatively in the brains of 303 mentally retarded adults 23 to 90 years of age at the time of their deaths (mean = 59.5 years). Cases with Down's syndrome, hydrocephalus and metabolic disorders were excluded from the study. Examinations of frontal, temporal, parietal, and occipital cortex, as well as hippocampus and parahippocampal gyrus were made in every case. NPs and/or NFTs were observed within the brains of 163 cases (53.8%). Detailed analyses indicated that NP density within all brain regions examined was positively related to age, with the largest age associated increases in density seen in frontal and temporal regions. In contrast, NFT density increased with age only within hippocampus and parahippocampal gyrus, but not neocortex. In addition, NP lesions within neocortex were more diffusely distributed across regions for older compared to younger cases, while no similar age-associated change in the topography of NFTs was observed. Finally, factor analyses of the combined NP and NFT data indicated that, while strong correlations existed across the various brain regions for measures of NP and NFT densities, considered separately, there was virtually no indication of regional associations between these two types of lesions. While these data, from cases with mental retardation, cannot be generalized directly to the nonretarded population, they provide strong evidence that models of Alzheimer pathogenesis must take into account the fact that regional densities of NPs and NFTs, and, therefore, the underlying processes associated with formation of these lesions, can be largely independent. PMID- 8460534 TI - The heterogeneous temporal evolution of focal ischemic neuronal damage in the rat. AB - Male Fisher rats (n = 61) underwent permanent focal cerebral ischemia induced by left middle cerebral artery (MCA) occlusion, in conjunction with ipsilateral common carotid artery ligation. The experiments were terminated at time points ranging from immediately following occlusion to 30 days post MCA occlusion. A coronal histological section, in close proximity to the site of the arterial occlusion, was taken from each brain and divided into six areas encompassing the affected cortex and caudate putamen. Each area was analyzed for ischemic damage according to a grading scale that reflects changes in neuronal morphology. Differential neuronal counts were also made on a 0.5-mm2 field in each of the six areas. The areas closest to the occluded vessel showed accelerated ischemic damage between 8 and 12 h after occlusion, leaving open the possibility that before 8 h, therapeutic intervention may be effective. After 12 h, changes in these areas progressed to complete necrosis and eventual cavitation with a complete loss of neurons after 10 days. The areas more peripheral to the occluded vessel exhibited mild ischemic damage, with an apparent reversal of damage grading at later time points and no loss of neurons. This reversal of ischemic damage in the peripheral areas is suggestive of a histological equivalent of the penumbra. PMID- 8460535 TI - The topographic distribution of brain atrophy in frontal lobe dementia. AB - The topographic distribution of brain atrophy was quantified by image analysis of fixed brain slices from ten patients dying with dementia of frontal type (DFT) and from six other patients dying with dementia of frontal type with motor neurone disease (DFT + MND). In both groups the atrophy was maximal within frontal, anterior temporal and anterior parietal regions of cortex, although other structures such as the amygdala, caudate nucleus, thalamus and hippocampus were also affected. The magnitude of the atrophy was much greater, in all affected regions, in DFT alone than in DFT + MND. Grey and white matter were affected equally in DFT alone although in DFT + MND a preferential white matter involvement was noted. No differences in the topographic distribution of the atrophy was observed in cases of DFT showing a spongiform degeneration of the cortex compared to those showing a gliotic degeneration with, or without, Pick cells and Pick bodies. PMID- 8460536 TI - Type C Niemann-Pick disease in a boxer dog. AB - Pathological and biochemical studies were performed on a 9-month-old boxer dog with progressive neurological abnormality. Histological examination revealed marked neuronal storage throughout the central nervous system and histiocytic storage in the reticuloendothelial system. Ultrastructurally, the neuronal storage consisted of accumulation of concentric membranous inclusions and clusters of dense bodies. The biochemically unesterified cholesterol content was high in the liver and spleen. The brain showed increased levels of lactosylceramide and two gangliosides, GM3 and GM2. These findings indicate that this dog was affected with a heterogeneous lipid storage disease similar to the human Niemann-Pick type C disease. PMID- 8460537 TI - Recent advances in breast feeding. AB - Increasingly, epidemiological studies are showing the benefits of exclusive breast-feeding to infants in industrialized countries, as they have previously for those in developing countries. In this review we have focused on several recent developments, in particular on the interplay between infant behaviour and maternal physiology in regulating breast milk supply. This will illustrate that many past and current clinical problems concerning breast-feeding are likely to be of iatrogenic origin, the products of imposing arbitrary rules for breast feeding management. In order for the protective benefits to be fully realized it is necessary to ensure that breast-feeding is free from prescriptive practices. We will illustrate the key role played by the infants' control of appetite in the hope of encouraging clinicians to empower infants to exercise more control over the feeding process. PMID- 8460538 TI - Two color flow cytometric analysis of lymphocytes in HTLV-I carrier children. AB - Phenotypic changes in lymphocytes from healthy children with antibody for human T lymphotrophic virus type I (HTLV-I) were studied using two color flow cytometry. The subjects were high school students within a small district of Kyushu, Japan. In the carrier group, a subset of lymphocytes which expressed CD8+CD57+ was significantly lower in percentage (P < 0.01) and in number (P < 0.05). There was no significant difference between carriers and non-carriers in the percentage and number of CD4+Leu8+ cells or CD4+HLA-DR+ cells. The IgG levels were slightly higher in carriers than in non-carriers (P < 0.05). These findings suggest that HTLV-I-infected cells may affect the immune system in healthy carrier children. PMID- 8460539 TI - The in vivo and in vitro postantibiotic effect of aminoglycosides using a clinically isolated micro-organism. AB - We reported a case of abscess in which Serratia marcescens was isolated as the causative organism. We measured the postantibiotic effect (PAE) of dibekacin (DKB) and gentamicin (GM) against S. marcescens and studied the relationship between the clinical effect and the PAE. The minimal inhibitory concentration (MIC) of DKB against S. marcescens was 6.25 micrograms/mL and the serum concentration 30 min after infusion of 100 mg DKB was 5.99 micrograms/mL. The abscess was cured by the administration of DKB every 12 h. The PAE in vivo was 2.5, 2.9 and 3.3 h when DKB was administered at 50 mg/kg, 100 mg/kg and 200 mg/kg, respectively. This PAE is one of the reasons that infection can be effectively treated with intermittent administration, even if the serum concentration is below the MIC. PMID- 8460540 TI - Growth and growth hormone secretion in children after bone marrow transplantation. AB - Long-term sequelae of bone marrow transplantation (BMT) are a major concern among long-term survivors since the procedure has been considerably developed over the past decade. In this study, linear growth and growth hormone (GH) secretion were evaluated in 25 children (14 males and 11 females) with various neoplastic or non neoplastic hematological disorders who had survived for more than 3 years after BMT. Impaired linear growth after BMT, as defined by a change in height standard deviation score (SDS) by more than -1.0 SD, was observed in 14 patients (56%). Four children showed severe growth suppression with a decrease in SD score by more than 2.0, and 10 exhibited a moderate reduction by between 1.0 and 2.0 SD. A recovery of normal height velocity was observed in those who had received BMT at a younger age. The type of disease, a difference in preconditioning regimen, the presence of chronic graft-versus-host disease or a GH secretory capacity 1 year after BMT were not contributing factors for impaired growth. A serial examination of GH secretion with insulin-induced hypoglycemia demonstrated that poor GH secretion was not necessarily a prerequisite for impaired growth. These results indicate that the secretory status of GH does not predict the future growth pattern of children who received BMT. PMID- 8460541 TI - Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome. AB - The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1-15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality. PMID- 8460542 TI - Management of colorectal polyps in children. AB - Forty-two patients each with a colorectal polyp have been treated in our hospital over the past 10 years. In twenty-two cases the polyps were noted in the rectum, nine in the sigmoid colon, seven in the descending colon and four in the transverse colon. Each patient had only one polyp. Hematochezia was the main symptom in 29 patients, prolapse of the polyp from the anus in 10, abdominal pain due to intussusception in two and no symptoms were observed in one. Auto amputation of the polyp was considered to have occurred in five patients. Twelve rectal polyps were resected from a transanal operation, and another 25 polyps were removed endoscopically with electric cautery. We have had no experience of endoscopic complications such as bleeding or perforation. A histological examination revealed an adenoma in one patient. Other polyps were non-neoplastic and were classified as juvenile, inflammatory and hyperplastic in 30, two and four patients, respectively. There have been no recurrences of polyps to date. PMID- 8460543 TI - Irradiated fetal thymus transplantation in a patient with combined immunodeficiency with predominant T cell defect. AB - A 6 month old boy was diagnosed as a case of combined immunodeficiency (with predominant T cell defect by previous classification). His T cell count was decreased, his B cell count in peripheral blood was increased, his serum IgG level was decreased, his serum IgM level was normal and the thymus was not evident on CT scans and magnetic resonance imaging. Administration of the thymus hormone, thymosin, led to a partial recovery of T cell function without normalization of the T cell count. At age 26 months the patient received an irradiated thymus transplantation from a 16 week old female fetus. After the transplantation, the T cell count (mainly CD4+ cells) increased by 50-70%. A mild graft-versus-host reaction (GVHR) occurred and several immunosuppressants were prescribed. Chromosome analysis showed that the T cells have both 46 XY and 46 XX karyotypes while the B cells have the 46 XY karyotype alone. His cellular immunity (skin tests, DNA synthesis, mixed lymphocyte reaction, cytotoxic activity and natural killer cell function) and his serum IgG level remained low. However, being on regular r-globulin therapy and oral anti-fungal drugs, he is now living normally with almost no trouble at age 6 years and 3 months. This case showed that irradiated thymus transplantation might be a useful method when an adequate donor for bone marrow transplantation is not available. The unexpected observation that the increased T cells were mainly CD4 may be related to the mild GVHR and the clinical improvement. PMID- 8460544 TI - Peripheral expansion of gamma delta T cell receptor-positive cells in a patient with Crohn's disease. AB - A 13 year old boy with Crohn's disease had a prominent expansion (over 40%) of gamma delta T cell receptor-positive cells (gamma delta T cells) in the peripheral blood. The gamma delta T cells were gradually decreased from 48 to 22% in 18 months. Anti-gamma delta T cell receptor-triggered cytotoxicity was evident at onset and after 1 year. The significance of peripheral expansion of gamma delta T cells in a patient with Crohn's disease is discussed. PMID- 8460545 TI - Treatment of an infant with congenital sodium diarrhea by oral rehydration. AB - We have been following a male case of congenital sodium diarrhea (CNaD), who had a distended abdomen, passed watery stools with high sodium concentration, and showed metabolic acidosis in the first week of life. He also showed hyponatremia, low urine sodium, high serum aldosterone and high renin activity. Other possible causes of secretory diarrhea were ruled out. The initial effective treatment was oral supplements of water and electrolytes lost in the fecal fluid: with this he gained weight, and hyponatremia and metabolic acidosis were corrected. Loperamide hydrochloride was administered to increase intestinal absorption of sodium, as the serum prostaglandin was high. Watery diarrhea then improved, but as he passed acholic stools, we stopped and postponed the treatment for a while; the stools then became watery again. Although diarrhea has persisted, he has not shown any abnormalities in growth or psychomotor development for the first two years of life. PMID- 8460546 TI - Inflammatory esophagogastric polyp and fold in an adolescent. AB - The case of a 13 year old boy with an inflammatory esophagogastric polyp and ulcerative colitis is described. Endoscopy revealed a typical polyp and gastric fold complex at the esophagogastric junction and a hiatal hernia. Histology of a biopsy specimen confirmed an inflammatory polyp covered by hyperplastic squamous and gastric foveolar epithelium. Continuous 24 hour esophageal manometry suggested gastroesophageal reflux, which may be related to the pathogenesis of the lesion. Follow-up endoscopy showed marked regression of the polyp with medication for reflux esophagitis. This clinical entity is rare in childhood and adolescence, and the manifestations may not be readily recognized. Therefore, endoscopic biopsy is important in children with esophageal polyps. However, polypectomy is unnecessary except when malignancy is suspected or when symptoms persist. PMID- 8460547 TI - Transient scoliosis in a child with juvenile rheumatoid arthritis. AB - An 8 year old girl was admitted to hospital complaining of arthralgia in a few large joints. According to the clinical course and serological tests, a diagnosis of a polyarticular type of juvenile rheumatoid arthritis was made. About 6 weeks after the onset, scoliosis was observed. The curvature regressed spontaneously over the following 6 months. Generally, scoliosis associated with juvenile rheumatoid arthritis has been noted a few years after the onset. A transient scoliosis in the early phase of this disease is rare. PMID- 8460548 TI - An autopsied case of Williams syndrome complicated by moyamoya disease. AB - An 18 year old girl with typical clinical features of Williams syndrome suddenly died of intracerebral hemorrhage due to moyamoya disease. Autopsy revealed vascular abnormalities, such as supravalvular aortic stenosis (SAS) and an abnormal complicated cerebrovascular network in the cerebral arteries. The arterial wall of the SAS lesion consisted of thickened medial tissue showing elastic disorganization with prominence of the smooth muscle cells. The narrowed vessels of the circle of Willis showed intimal thickening with an extremely wavy internal elastic lamina and marked thinning of the media. To our knowledge, this is the first report of moyamoya disease associated with Williams syndrome. PMID- 8460549 TI - Ultrasonographic evaluation of abdominal vessels in Kawasaki disease. PMID- 8460550 TI - Abnormal findings in the signal-averaged electrocardiogram in patients with Ebstein's anomaly. PMID- 8460551 TI - Distribution of lectin receptors in the human hyperplastic tonsil: histochemical and flow cytometric analyses. AB - The distribution of lectin receptors in the human tonsil was studied using 16 biotinylated lectins. The avidin-biotin-peroxidase complex (ABC) method was used on frozen and paraffin-embedded tissue sections. Cell suspensions were also analysed by dual flow cytometry using respective fluorescein isothiocyanate conjugated lectins and phycoerythrin-labeled anti-CD3 and anti-human immunoglobulin. Frozen sections fixed with acetone and paraffin-embedded materials fixed in three solutions were compared for lectin affinity; ethanol fixed sections gave best results followed by frozen and buffered formalin-fixed ones, then nonbuffered formalin. Con-A, RCA-1, LcH, WGA, MPA, PHA, PSA, PNA, SJA and GSA-1 reacted with all tissue components of the tonsil in immunohistochemical studies, but binding intensity was fixative dependent. Binding of Lotus and BPA to lymphocytes was limited to germinal center lymphocytes. Other tissue components were also reactive but staining intensity was weaker in Lotus compared with BPA. SBA and DBA did not react with lymphocytes, but reacted with macrophages/histiocytes, vascular endothelia, and epithelial cells. LBA and LPA were constantly negative with all tissue components irrespective of fixatives. Flow cytometric analyses showed that all but three (DBA, LBA and LPA) partially or totally stained lymphocyte surfaces. Lotus receptors were expressed exclusively on B-lymphocytes. PMID- 8460552 TI - Inhibition of liver regeneration in mice following extended hepatectomy by transfusion of lymphokine activated killer cells. AB - Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic liver cells. In this study, the effects of passive transfer of LAK cells on liver regeneration were examined by the 3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% of the volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36 h later. The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10 x 10(7) cells. Neuraminidase treatment of lymphocytes is desirable to enhance the selective entrapment of LAK cells into the liver. When LAK cells were treated with neuraminidase (0.5 units/ml), and transfused into hepatectomized mice, more potent suppression of liver regeneration was induced in comparison with the same dose of LAK cells. The intraperitoneal injection of recombinant interleukin 2 (rIL-2) after partial hepatectomy also inhibited the regeneration of remnant liver. From these results, lymphocytes such as LAK cells appear to regulate liver regeneration. PMID- 8460553 TI - Hemostasis of gastric variceal hemorrhage by transileocoecal and transhepatic obliteration. AB - Obliteration for gastric or duodenal variceal hemorrhage was performed via transileocoecal or transhepatic portal catheterization in 8 patients with portal hypertension. The patients were 6 men and 2 women, whose average age was 59 years. All of the patients had cirrhosis of the liver. The obliteration was performed as an emergency procedure in 6 cases, and 2 patients were electively treated. Transileocoecal obliteration (TIO) and transhepatic obliteration (PTO) were selected for 6, and 2 patients, respectively. Variceal bleeding was successfully controlled in all patients after completion of the therapy. One patient died after 3 months when duodenal variceal bleeding recurred. Elective surgical operations were performed on 2 patients after the initial therapy, because the vein feeding toward the varices remained. Six of the patients have survived to date without bleeding. Transient oliguria and jaundice after the therapy were noticed in 2 patients. Histological examination revealed cast formation of polymerized cyanoacrylate in the obliterated gastric varices of 2 patients. TIO and PTO seem to be safe, effective procedures to stop bleeding from ectopic varices, gastric or duodenal. This therapy is useful either to obtain accurate information about the varices or to obliterate the collateral veins in patients with ruptured ectopic varices. PMID- 8460554 TI - Efficacy of percutaneous transluminal coronary recannalization for preservation of the post-infarct left ventricular regional wall motion: a trial of the evaluation by weighting coronary artery segments. AB - Efficacy of the percutaneous transluminal coronary recannalization (PTCR) therapy was evaluated by weighting infarct-related coronary artery segments in 28 consecutive patients with acute myocardial infarction. The study focused on the influences of the time interval from the onset of chest pain to PTCR (PTCR-Time) and on the post-infarct left ventricular regional wall motion in conjunction with the serum levels of GOT, LDH and CPK and with PTCR-Time. PTCR success rate was 84.0%, and re-occlusion rate was 4.0%. The thrombolysis in myocardial infarction grade 2, however, was observed in 7 (33.3%) of 21 cases with successful PTCR. There was no significant difference in PTCR-Time between the PTCR success and nonsuccess groups. Significant correlations were observed between the PTCR-Time and each peak value of standardized serum levels of LDH and CPK, and between the PTCR-Time and the post-infarct regional wall motion abnormality. There were also significant correlations between the standardized serum level of each of these three enzymes and the post-infarct regional wall motion abnormality. It was clearly demonstrated that the earlier the recannalization of the infarcted artery was achieved, the less extensive the myocardial damage in quantitative and qualitative aspects. PMID- 8460555 TI - Evaluation of radiograph signs for the diagnosis of solitary peripheral pulmonary nodules less than 3 cm. AB - Ten radiograph signs were assessed by two experts for their usefulness in the diagnosis of small solitary peripheral pulmonary nodules less than 3 cm. The ten categories included notching, spicula formation, pleural indentation, vascular convergence, contour, paleness, homogeneity, cavitation, air bronchogram, and calcification. The cases included 134 lung cancers and 44 benign lung lesions resected between 1972 and 1988 at the Second Department of Surgery, Okayama University Medical School. Notching, spicula formation, pleural indentation, vascular convergence, contour, and air bronchogram were useful signs in differentiating lung cancer from benign lung lesions. However, since the radiograph signs exhibited great variation in both lung cancer and benign lung lesions, a diagnostic operation is sometimes inevitable. PMID- 8460556 TI - A case of chronic pancreatitis with pseudoaneurysm rupturing into a pseudocyst. AB - A 44-year-old man with alcohol-induced chronic pancreatitis was referred to our institute for evaluation of severe anemia. The hemoglobin was 2.6g/dl. The results of upper gastrointestinal and colonic examination were negative. Computed tomography and ultrasound examination revealed a pseudocyst in the head of the pancreas. A pseudoaneurysm of the anterior superior pancreaticoduodenal artery shown by angiography appeared to have caused gastrointestinal bleeding by rupturing into the pancreatic cyst connected to the main pancreatic duct. A pyrorus-preserving pancreaticoduodenectomy was performed successfully. PMID- 8460557 TI - Solitary pancreatic metastasis from renal cell carcinoma. AB - A rare case of resectable solitary pancreatic metastasis from a renal cell carcinoma is reported. The patient was a 57-year-old man who presented with epigastralgia. He had undergone a radical nephrectomy of the right side 30 months previously. The diagnosis of pancreatic metastasis was based on the patient's past history and angiographic demonstration of typical hypervascular tumor staining. Histological examination was confirmatory. The patient was successfully treated by pancreaticoduodenectomy followed by alpha-interferon administration. As of 6 months after surgery, he remains well. PMID- 8460558 TI - Effective preoperative and postoperative respiratory training in a lung cancer patient with chronic respiratory failure. AB - A case illustrating the value of aggressive respiratory training in improving the prognosis of lung cancer complicated by low pulmonary function is reported. Preoperative and postoperative respiratory training enabled the patient with chronic respiratory failure to survive a lengthy operation and eventually breathe without assistance. The patient has survived more than 71 months, and experiences only exertional dyspnea at the time of publication. Aggressive preoperative and postoperative respiratory management may make more of the growing number of lung cancer patients eligible for standard surgical procedures. PMID- 8460559 TI - Rat liver epidermal growth factor receptors in intrauterine growth retarded and heavy-for-date fetuses. AB - We recently reported that epidermal growth factor (EGF) levels in the first urine to be voided by intrauterine growth retardation (IUGR) and heavy-for-dates (HFD) infants were lower than control infants (8). In this study, we analyzed EGF receptors to reveal the mechanisms controlling EGF levels. EGF binding to fetal rat liver increased markedly from day 19-21 of gestation. Fetal rats were divided into IUGR, control and HFD groups. EGF binding to the liver in each group was as follows, IUGR; 380 +/- 57 fmol/mg protein, control; 258 +/- 47, and HFD; 545 +/- 112. The binding to IUGR and HFD rat liver was significantly greater than in the control group (p < 0.05). These data suggest that IUGR rats compensate for a lack of EGF by increased receptor expression and that HFD rats consume more EGF and have decreased urinary EGF excretion. These data also suggest that EGF is closely related to fetal growth and may play some important roles in fetal growth. PMID- 8460560 TI - Surgical management of haemangioblastoma of the posterior fossa. AB - Fifty-one cases of posterior fossa haemangioblastoma have been seen in our department over a period of 23 years. Seven cases were associated with spinal cord lesions and one with a supratentorial lesion. There were 22 cases of Lindau's disease (43%). The onset was earlier and recurrences commoner than in isolated cases. In 10 cases the development of new tumours in different parts of the central nervous system (CNS) required re-operation, demonstrating the multicentric nature of this disease. The majority of the tumours occupying the fourth ventricle or medulla oblongata (8 cases) were macroscopically solid and had higher post-operative morbidity than the cystic tumours in the cerebellum. The recent development of magnetic resonance imaging (MRI) provides accurate anatomical information of the lesions (especially those of the brain stem and spinal cord) even while asymptomatic. The brilliant enhancement of these tumours on MRI with Gadolinium-diethyline-triamine-pentaacetic acid (Gd-DTPA) has proved to be particularly useful. PMID- 8460561 TI - Pituitary apoplexy: endocrine, surgical and oncological emergency. Incidence, clinical course and treatment with reference to 799 cases of pituitary adenomas. AB - Authors analyzed retrospectively the incidence of pituitary apoplexy in a series of 799 pituitary adenomas with respect to the long term follow-up of the patients. Focal vascular abnormalities in histological specimens of tumours, regarded as morphological suggestion of past apoplexy (haemorrhage, ischaemic infarction or necrosis), were established in 113 out of 783 surgical cases (14.4%). Acute clinical onset, justifying the clinical diagnosis of pituitary apoplexy, occurred in 39 patients only (5% of the whole series), 19 of them were subjected to urgent surgical decompression due to severe neurological deficit. The haemorrhagic character of apoplexy was established in most cases requiring immediate surgery. The detailed clinical picture of this condition and its management are discussed with respect to the long term prognosis. On this basis the authors suggest the necessity of surgical treatment in every case of pituitary apoplexy, taking into account not only neurological recovery, but also endocrine and oncological aspects of the disease. The observation that pituitary apoplexy may be a "marker" of tumour invasiveness (even in small, "enclosed" adenomas) is highlighted. PMID- 8460562 TI - Neuropsychological evaluation in a series of 17 cases operated on for craniosynostosis. AB - In a study of patients suffering from craniosynostosis various pre- and post operative parameters were identified that may affect subsequent intellectual capacity. In particular, facial malformations appeared to be closely correlated with impaired intellectual development. Other parameters included measurement of cranial circumference and volume; their subaverage values correlated with slight mental insufficiency. However, in the pre-operative period they cannot be used as prognostic indices because these relations were statistically not significant. The remaining parameters (neurological and electroencephalographic findings, post operative re-ossification of the skull, pre-operative digital impressions, CT findings) did not seem to be related to intellectual development. PMID- 8460563 TI - T-bone plastique for treatment of brachy-turricephaly. AB - The "T-Bone Plastique", which is presented in this paper, allows a surgical correction even of extreme cases of brachy-turricephaly together with malformations of the occipital region in one operative session. Brachy turricephaly is characterized by abnormal vertical height of the skull and a shortening of its anterior-posterior length, frequently combined with malformations of the occipital region. Resection of the prematurely closed coronal suture, bi-parietal trepanations with 90 degrees rotation and side exchange of the parietal bone flaps, double transverse trepanation of the occipital bone and outward bending and shifting of the bone fragments enable a bony remodeling and normalization of the deformed skull. Using this operative technique in three children we achieved a significant improvement of the skull form with an aesthetically pleasing result, without any neurologic sequelae and with normal development of the children during follow-up. PMID- 8460564 TI - The Glasgow Coma Scale: a mathematical critique. AB - The Glasgow Coma Scale permits 120 possible mathematical combinations of eye, verbal and motor scores. Out of these only about 15 are clinically valid and useful in the assessment of altered consciousness. A mathematical analysis of this pruned scale shows a predominant skew towards the motor response. Without clinically altering the scale. The numerical values can be modified to produce a more equitable dominance by each of the factors and greater precision. This is also necessary as the value of a unit is the same in the sum score, whether contributed by the eye, verbal or motor elements. PMID- 8460565 TI - Surgical management of neurogenic claudication in 100 patients with lumbar spinal stenosis due to degenerative spondylolisthesis. AB - 100 consecutive patients with neurogenic claudication due to segmental spinal stenosis in degenerative spondylolisthesis have been analyzed prospectively with respect to their clinical presentation, radiological and intra-operative findings, operative techniques and surgical results. By including 6 patients who had to be operated upon again overall results were excellent in 91, good in 4, satisfactory and moderate in 2, respectively, and poor in 1 patient (mean period of postoperative observation: 2.9 years). Three different techniques of spinal instrumentation are evaluated with respect to the surgical results. After microsurgical decompression of the neural elements 38 patients were fixed using the translaminar screw fixation method according to Magerl (re-operation necessary in 5), in 9 patients spondylodesis was achieved by the plate fixation method according to Louis (re-operation necessary in 1) and in 53 patients (as well as in the 6 patients who had to be re-operated on) primary Cotrel-Dubousset instrumentation was used. The best surgical results were obtained by laminectomy and Cotrel-Dubousset fixation. Instrumentation of more than 1 motion segment was restricted to patients with additional scoliosis or severe degenerative changes of the lumbar spine. PMID- 8460566 TI - Microsurgical treatment of lumbar disc herniation: follow-up of 237 patients. AB - We have reviewed retrospectively the results of 237 consecutive patients who underwent microsurgical discectomy for a virgin lumbar disc herniation. Included were 128 (54%) mean and 109 (46%) women, with the mean age of 42 years. Intra operatively, protrusion was found in 60 (25%) patients, prolapse in 127 (54%) patients and sequestration in 50 (21%) patients. The median post-operative follow up time was 2 years. During the observation period, sciatic pain had completely recovered or markedly diminished in 218 (92%) patients, and 187 (79%) patients had returned to work. The mean duration of preoperative sciatica was 3.8 months in those patients who finally returned to work. In contrast, it was as long as 6.3 months in those patients who lost their working capacity as a consequence of low back pain. The patients operated on for a prolapse or a sequestrum recovered better than those who underwent surgery for a protrusion. Of the patients operated on for a protrusion, 68% returned to work, while 76% of those operated on for a sequestrum and 85% of those operated on for a prolapse returned to work during the follow-up. Difference was seen also in the occupational outcome: only 37% of the patients operated on for a protrusion reported to manage their work well, while 47% of those with a prolapse and 58% of those with a sequestrum managed well. Surgical complications were infrequent in this study. Dural tear appeared in 10 (4%) patients and post-operative discitis in 4 (1.7%) patients. Of all patients, 9 (4%) required re-operation for a true recurrent disc. PMID- 8460567 TI - Peri-operative elastase-alpha-1 proteinase inhibitor in patients with postoperative intervertebral discitis. AB - In a prospective study of 251 patients operated upon for lumbar disc herniation it has been investigated whether the preoperative and early postoperative values of Elastase-alpha-1 Proteinase Inhibitor (EPI)-an indicator of inflammatory processes-and C-reactive Protein (CRP)-a well known predictor of some postoperative complications-were correlated to the later development of discitis. Postoperatively discitis developed in 14 patients. A randomly chosen group of 15 complication-free patients out of the total of 251 cases was used as control group. Elevated EPI plasma values, especially in the pre-operative and first postoperative days, turned out to be significantly related to the likelihood of later discitis development, but no such relation for the CRP plasma values could be established. Thus and early prediction of patients at risk for this complication seems to be possible by pre- and postoperative measurement of EPI. It could be justified-but its usefulness has yet to be proven-to give antibiotics prophylactically and other anti-inflammatory medication in patients with elevated pre- and postoperative EPI values. PMID- 8460568 TI - Conjoined lumbosacral nerve roots. AB - Conjoined lumbosacral nerve roots is a congenital anomaly that may produce lumbosciatic pain. When symptomatic and undiagnosed, it may be one of the causes of failed back syndrome. Diagnosis with water-soluble contrast myelography has a frequency of 4%. Anatomical studies have shown to have an incidence of 14%. High quality Magnetic Resonance Imaging (MRI) with coronal views may reveal this condition without recurring to computed tomography (CT)-myelography. In this paper we describe our recent experience with five consecutive cases observed during a one year period. PMID- 8460569 TI - Effect of fibrin glue on postlaminectomy scar formation. AB - An experimental study in rats has been carried out with the aim of studying the scar formation over the spinal dura in the presence of fibrin glue. Although the main action of fibrin glue is the enhancement of wound healing by increasing the fibrous tissue, our present data suggest that this re-absorbable biomaterial diminishes the epidural scar formation, at least the first two weeks after laminectomy. This finding leads us to consider the use of fibrin glue over spinal duramater when it is likely that reoperation may become necessary in a short period of time after a laminectomy. PMID- 8460570 TI - Neuropathological and neurophysiological effects of interstitial white matter autologous and non-autologous protein containing solutions: further evidence for a glioma derived permeability factor. AB - The feline infusion model of brain edema was used to evaluate the pathophysiological effects of 0.6 ml infusions of autologous serum protein (66%), human serum protein (66%), human glioma cyst fluid and a tissue culture medium (TCM) on the structure and function of the forebrain white matter. These infusions increased local white matter water content by between 10.8 and 12.5 ml/100 g brain and were associated with moderate increases in ICP and CSF outflow resistance and a significant decrease in lumped craniospinal compliance. Cortical somatosensory potentials, motor evoked potentials, EEG and local cerebral blood flow (rCBF) at normocapnia were generally unchanged by the various infusions. All infusates except the 66% autologous serum protein infusion impaired rCBF CO2 reactivity. Histologically all infusates caused marked extracellular edema. The autologous serum protein infusion caused no additional histological changes whereas the glioma cyst infusates caused profound endothelial and astrocytic swelling, focal endothelial necrosis, basement membrane disruption, perivascular microglial reaction and pavementation and perivascular migration of polymorphonuclear leukocytes. Similar but less marked changes were seen after infusion of human serum protein whilst the TCM produced only minimal changes. The intensity and extent of Evans Blue extravasation into the forebrain white matter was greatest with glioma cyst infusates and with all infusions reflected the extent to microvascular changes. These studies show that products derived from gliomas cause additional damage to the blood-brain-barrier than that caused by non-autologous serum proteins. These results add further support for the existence of glioma derived permeability factors (GDPF), but suggest neither serum proteins nor glioma derived compounds in the white matter interstitium significantly influence local electrophysiological function. Some limitations of the infusion edema model when using non-autologous infusions and difficulties quantitating brain dysfunction are emphasised. PMID- 8460571 TI - Topical effect of bromocriptine on rat-transplanted human prolactinomas. AB - In prolactinoma surgery, especially in macro-adenomas, it is not always possible to remove the tumour totally. Cell remnants may cause a regrowth and continue hypersecretion. In order to find out whether tumour remnants could be destroyed by local application of bromocriptine, a research model has been designed. First, prolactin secreting pituitary tumours, removed during surgery, were implanted bilaterally into the brain tissue of rats. In eight rats, the viability of tumour transplants was proven histopathologically and their prolactin secretion was shown immunocytochemically. In a second step, on eight rats, sterile bromocriptine solution was applied topically to the tumour transplants on one side. The other side served as control. Histopathological examination of these treated tissues revealed fibrosis. Immunocytochemical analysis showed no secretory activity. Ultrastructural investigations also revealed evidence of degeneration of the treated cells. The natural course of the transplanted tumour tissues of the other side, as a control group, was also observed during the same 55-day period. PMID- 8460572 TI - Effect of superoxide dismutase on acute reperfusion injury of the rabbit brain. AB - To study the involvement of free oxygen radicals of the blood-brain barrier (BBB) disruption during early reperfusion, we isolated the distal internal carotid artery, and the middle and anterior cerebral arteries via the transorbital approach in anesthetized rabbits. Using radiolabeled microspheres, regional cerebral blood flow (rCBF) was measured before, during and after 1-hour unilateral occlusion of these vessels. Fifty-five minutes after ischemia, animals received intravenous saline placebo (control), superoxide dismutase (SOD) at 8 mg/kg = 30,000 U/kg, or weakened superoxide dismutase (wSOD) at 8 mg/kg = 30,000 U/kg. Integrity of the BBB was assessed by leakage of Evan's Blue-albumin dye (EB albumin dye), which was given at 15 minutes of reperfusion and allowed to circulate for an additional hour. In the control and wSOD-treated groups, rCBF decreased (26% and 40% of control, respectively) within the blue-tinted tissue of the occluded hemisphere during ischemia; hyperemia was observed during early reperfusion. In the control and wSOD-treated groups, EB-albumin dye leakage across the BBB increased 49% within the occluded hemisphere. However, within the SOD-treated group, the BBB showed minimal dye leakage even though rCBF of the occluded hemisphere (so-called blue-tinted tissue) decreased by 38% during ischemia. We conclude that 1-hour focal cerebral ischemia and reperfusion produce a vascular endothelial injury at the BBB. Since SOD administration showed significant protection, free-oxygen-radical production during early reperfusion is associated with breakdown of the BBB to large molecules. PMID- 8460573 TI - Serial regional blood flow and visual evoked responses in transient cortical blindness. AB - Normal regional blood flow was documented by Single Photon Emission Computed Tomograms 5 and 20 hours before the full recovery of cortical blindness in two patients, lending itself to the possibility of being a prognostic factor. Rubbing of the posterior cerebral arteries against the tentorial edges during trauma instead of traction was believed to cause blindness in one patient and embolization due to hammering bone grafts home during cervical spinal fusion, in the other. Pattern reversal visual evoked responses (PRVERs) were absent during blindness; upon recovery P 100 with full amplitude and normal latency appeared despite the presence of tunnel vision. These are consistent with the fact that the central 8-10 degrees of visual field represented in the posterior occipital poles being the main sources of P 100 in association with the x-cells in the centre of the retina. PMID- 8460574 TI - Poikilothermia in a female patient with a germinoma in the basal ganglia. AB - An unusual association of poikilothermia and a germinoma originating in the left basal ganglia is described in a 17-year-old female. The tumour was found extending into the hypothalamic structures. Following irradiation therapy, the patient gradually regained her regulation of body temperature. PMID- 8460575 TI - Artificial intelligence and the supervision of bioprocesses (real-time knowledge based systems and neural networks). AB - The ability to supervise and control a highly non-linear and time variant bioprocess is of considerable importance to the biotechnological industries which are continually striving to obtain higher yields and improved uniformity of production. Two AI methodologies aimed at contributing to the overall intelligent monitoring and control of bioprocess operations are discussed. The development and application of a real-time knowledge-based system to provide supervisory control of fed-batch bioprocesses is reviewed. The system performs sensor validation, fault detection and diagnosis and incorporates relevant expertise and experience drawn from both bioprocess engineering and control engineering domains. A complementary approach, that of artificial neural networks is also addressed. The development of neural network modelling tools for use in bioprocess state estimation and inferential control are reviewed. An attractive characteristic of neural networks is that with the appropriate topology any non linear functional relationship can be modelled, hence significantly reducing model-process mismatch. Results from industrial applications are presented. PMID- 8460576 TI - Host-vector interactions in Escherichia coli. AB - Introduction of a DNA vector into E. coli for the purposes of cloned gene expression can perturb native cell functions at many levels. The presence of foreign DNA can alter regulation of chromosomal DNA replication, regulation of transcription of chromosomal genes, ribosome functions and RNA turnover, activities of regulatory proteins, chaperone and protease levels, membrane energetics and protein post-translational processing, as well as energy and intermediary metabolism of the cell. The combined effects of these interactions on the metabolic characteristics of the host-vector system have major implications for yields of cloned biotechnological products and interactions of genetically engineered organisms with their environment. PMID- 8460577 TI - Parameters influencing the productivity of recombinant E. coli cultivations. AB - In the past 10 to 15 years, many of the promises of microbial genetic engineering have been realized: the use of recombinant Escherichia coli has moved from the laboratory to the production facility, and the manufacture of therapeutic recombinant proteins such as human growth hormone and interleukins is a rapidly growing industry. Along with this progress, however, have come new problems to solve: bioreactor operators have discovered that large-scale cultivations of plasmid-containing bacteria do not behave in exactly the same way as those of plasmid-free cells, plasmid stability has been recognized as a major hurdle, and the protein product might not be present in a soluble form but rather as intracellular granules that resist solubilization. These and other difficulties represent a new generation of challenges for genetic engineering. However, genetic engineering can do more than solve these problems. Molecular biological techniques also have the ability to create new opportunities: to produce new compounds, to use cheaper substrates, to facilitate downstream processing, and to optimize production in new ways. The productivity of a cultivation can generally be expressed as the product of the cell density and the specific biological activity. Both of these parameters are influenced by a variety of factors. For recombinant cultivations, though, the level of biological activity, a reflection of the plasmid copy number and expression efficiency, is the more interesting and important consideration and will therefore be given more attention in our review. In this contribution, our general goal is to discuss the factors that influence the productivity of recombinant E. coli cultivations, covering parameters relating to DNA; parameters relating to protein synthesis; parameters relating to proteins; and parameters relating to downstream processing. The object is not to tell the reader how to choose the perfect plasmid, host, and cultivation conditions, but to make known the many variables involved in designing a recombinant process and to point out recent and potential advances made possible by genetic engineering. The discussion focuses on the production of a protein, but many of the same concepts apply to other cultivations of recombinant E. coli, including cases in which the desired product is not a protein or the cells have been designed for a special metabolic capability such as pollutant biodegradation. PMID- 8460578 TI - [Dementia, daily activities and micturition of the elderly living in a nursing home]. AB - This report shows the relation between daily activities, dementia and urinary disturbance. The subjects consisted of 44 males and 110 females with an average age of 80 years (ranged from 57 to 102). We evaluated the daily activities, underlying diseases, state of urination and the intelligence by the scale of Hasegawa. The persons with diapers had a higher degree of dementia than those who could go to the lavatory. As the degree of dementia aggravated, the incidence of urinary incontinence significantly increased. Urodynamic studies were performed on 49 persons who had urinary disturbance. There were 25 persons with normal vesical function, 16 with overactive vesical function, and 8 with underactive vesical function. Since all of the incontinent persons without dementia had abnormal vesical function, pharmacologic therapy was expected to be effective for them to improve incontinence. Half of the incontinent persons with dementia had normal vesical function. Mental and physical disabilities seemed to be the main factors causing incontinence in these persons. The multidisciplinary approach including medication, behavior treatment and awareness of the nursing staff is important and effective to reduce urinary incontinence. PMID- 8460579 TI - [Macrophage colony-stimulating factor for treatment of prostatic cancer with bone metastases]. AB - Macrophage colony-stimulating factor (MCSF) was used in the treatment of pancytopenia for a 64-year old man with prostatic cancer with bone metastases. Pancytopenia was improved and tumor markers (PA, PAP, gamma-Sm) were normalized rapidly after castration. The alkali phosphatase (A1P) concentration decreased to the normal range and bone metastases were improved markedly after two courses of chemotherapy. To determine the clinical efficacy of M-CSF against tumor markers and A1P, we used M-CSF on two other patients with prostatic cancer with bone metastases. In one of them, the levels of the tumor markers decreased from the initiation of the injection of M-CSF, but gradually increased to the initial levels after the last injection. The total A1P concentration was not changed by M CSF, but the A1P-3 concentration decreased and continued to decline. These findings suggest that M-CSF has an antitumor effect and that it can be effective in the treatment of prostatic cancer with bone metastases. PMID- 8460580 TI - [Adherence of bacteria to various urethral catheters and occurrence of catheter induced urethritis]. AB - To prevent the occurrence of nosocomial urinary tract infections among patients with indwelling urinary catheters, we compared commercially available catheters for the degree of irritation to surrounding mucosa and bacterial adherence. The hydrogel-coated catheter was found to be superior to the teflon-coated or silicone-coated catheters, since it had the lowest degree of bacterial adherence and mucosal irritation among these products. These findings suggest that the incidence of catheter-induced urinary tract infection would be lowered by the use of hydrogel-coated catheter, and recommend their use for patients requiring long term urinary catheterization. PMID- 8460581 TI - [Side effects of estrogen administration to prostatic cancer patients: clinical and statistical survey of 109 prostatic cancer cases of Kyoto University Hospital]. AB - Since the introduction of hormonal treatment for prostatic cancer by Huggins and Hodges in 1941, severe side effects of synthetic estrogen, which have overcome its benefit, have been reported in the U.S.A. and in European countries. However, in Japan the adverse effects of estrogen have been reported to be milder than in western countries, and estrogen still has an important role in the treatment of prostatic cancer in Japan. In this communication, the side-effects of synthetic estrogen administered to 109 prostatic cancer patients, who were admitted to Kyoto University Hospital between 1980-1990 are reported. Fifty-three (48.6%) of the 109 patients suffered adverse side effects of the estrogen, specifically cardiac disease (20.2%), fluid retention (14.7%) and hypertension (13.8%). Five of these patients died. Among the risk factors analyzed, daily dose, past history of cardio-vascular disease and ECG abnormalities were significantly correlated with the appearance of adverse effects. The reasons why the frequency of lethal side-effects is lower in our cases compared to findings reported by the Veterans Administration group may be the lower daily dose and cessation of estrogen administration when mild adverse effects appear and some other unknown factors, although the background of the patients and method of analysis are not comparable among them. The overall frequency of side-effects in prostatic cancer patients administered estrogen in our cases is not necessarily lower than in western countries, but the severity of the side effects was milder in our cases. We must be a ware of the potential adverse effects of estrogen. PMID- 8460582 TI - [A case of adrenal myelolipoma associated with renal cell carcinoma]. AB - A 41-year-old male patient was admitted to Maebashi Red Cross Hospital with a complaint of a left flank mass. Left renal tumor and contralateral adrenal mass were revealed by ultrasonography, computed tomography and magnetic resonance imaging. Endocrinological examinations were unremarkable. Left nephrectomy and right adrenalectomy were performed simultaneously. Histological findings of the left renal tumor confirmed clear cell carcinoma, and those of the right adrenal tumor revealed myelolipoma with mature adipose tissue and hematopoietic elements. PMID- 8460583 TI - [A case of adrenal myelolipoma incidentally discovered on abdominal ultrasonography]. AB - We report a case of adrenal myelolipoma occurring in a 58-year-old-woman. A tumor was incidentally detected in the right adrenal region by ultrasonography during admission to our hospital due to gastric ulcer. Ultrasonography revealed punctate calcification within the tumor. No endocrinologic abnormalities were demonstrated. CT revealed a nonhomogenous mass 5 cm in diameter that consisted of tissue with a fatty density and areas of calcifications. Retrograde femoral angiography demonstrated that the tumor was relatively hypervascular. Large blood vessels resembled sinusoids that were demonstrated by pooling of the contrast medium. Right adrenalectomy was performed. The histological diagnosis was adrenal myelolipoma. PMID- 8460584 TI - [A case of myelolipoma arising from accessory adrenal gland]. AB - A case of adrenal myelolipoma is reported. The patient was a 74-year-old female who was admitted to our hospital. Ultrasonography and CT scan incidentally showed a left retroperitoneal tumor, located between the left kidney and the spleen. At the operation, we observed that the tumor separated from the normal left adrenal gland, and confirmed that the tumor had developed from the accessory adrenal gland. The resected tumor measured 61 x 42 x 40 mm in size and 60 g in weight. Histological findings were compatible with myelolipoma. We reviewed 104 cases of adrenal myelolipoma reported in the Japanese literature. PMID- 8460585 TI - [Argyrosis of the urinary tract after silver nitrate instillation: report of a case]. AB - A 69-year-old woman was referred to our hospital for evaluation of pyuria and renal dysfunction. Twenty days earlier, the patient had undergone silver nitrate retrograde instillations for essential renal bleeding. Routine laboratory findings showed renal dysfunction with a serum creatinine concentration of 7.2 mg/dl and blood urea nitrogen concentration of 68 mg/dl. The urine contained numerous red cells and white cells. The plain X-ray film of the abdomen revealed right renal calcification. Computed tomographic scan confirmed the calcifications in the right renal collecting systems and parenchyma. The most likely diagnosis was argyrosis of the upper urinary tract. The patient underwent a right nephrectomy. Histopathological examination of the specimen showed that the renal pelvis was filled with blood clots. Laboratory evaluation including serum creatinine concentration and urinalysis revealed normal parameters postoperatively. We conclude that this patient developed argyrosis of the urinary tract, and review previously published papers concerning complications of silver nitrate instillation. PMID- 8460586 TI - [Multilocular cystic renal cell carcinoma: a report of two cases]. AB - Two cases of multilocular cystic renal cell carcinomas in a 48-year-old man and in a 41-year-old woman are reported. Radical nephrectomy was performed in both cases. Both histologic diagnoses were multilocular cystic renal cell carcinoma, clear cell subtype, grade 1. We had some difficulty in diagnosing the latter case with multilocular cystic mass which had smooth, glistening lining and contained clear-yellow fluid. Microscopical examination of the permanent sections revealed that the cysts were lined by a cuboidal or flattened epithelium, but no tumor cells. However, laminar growth of renal cell carcinoma of the clear cell type was present in several areas in the septa, and a few residual tumor cells were found in the hyalinized septa. When renal cell carcinoma is present in only a part of the multilocular cystic renal mass, it should be diagnosed as multilocular cystic renal cell carcinoma. The literature was surveyed. PMID- 8460587 TI - [Two cases of urinary tract abnormalities (ectopic ureterocele and VUR) associated with complete duplex kidney]. AB - Two patients with complete duplex kidney accompanied by ectopic ureterocele and vesicoureteral reflux (VUR) had repeated episodes of refractory urinary tract infection. One patient was a 11-year-old girl who showed VUR into the cele ureter. The other patient was a 17-year-old female who showed VUR into the mate ureter. Satisfactory results could be obtained by twin ureteroneocystomy with cele wall resection in both cases. Complete duplex kidney is often complicated by urinary tract abnormalities such as ectopic ureterocele, VUR, and renal dysplasia, and these complications complicate its diagnosis. The treatment of complete duplex kidney with urinary tract abnormalities are discussed. PMID- 8460588 TI - [A case of bilateral ectopic ureter in a male]. AB - A 7-year-old boy was admitted for recurrent pyelonephritis. Intravenous pyelography IVP showed right hydronephrosis and normal left kidney and ureter. Cystourethroscopy revealed no ureteral orifices in the bladder but bilateral ureteral openings adjacent to the seminal colliculus. Right retrograde pyelography showed severe hydroureter and hydronephrosis. The diagnosis was bilateral ectopic ureteral opening into proximal urethra. His abnormality of ureteral opening was classified as type II in Thom's classification. Bilateral ureterocystoneostomy was performed. Only 3 cases of bilateral ectopic ureter in males have been reported in the Japanese literature. PMID- 8460589 TI - [A case of retrocaval ureter treated in childhood]. AB - A case of retrocaval ureter in a 10-year-old boy is reported. His chief complaint was asymptomatic total macrohematuria. Physical examination and all laboratory findings were within normal limits, but drip infusion pyelography revealed a right hydronephrosis with "S shaped" ureter. The diagnosis was confirmed by enhanced CT scan. After follow-up for 1 year and a half, right uretero ureterostomy was performed because the severity of the hydronephrosis had increased. We review 25 cases of retrocaval ureter in childhood reported in the Japanese literature and compare the clinical characteristics between infant cases and adult cases. PMID- 8460590 TI - [Removal of migrated ureteral stent with a Fogarty catheter]. AB - A 64-year-old woman had undergone right percutaneous nephrolithotomy and transurethral ureteroscopy elsewhere. Stenosis of uretero-pelvic junction had occurred. Against the stenosis a double-J ureteral stent was placed within the right ureter and migration of the stent out of the bladder into the more proximal ureter was found after the stent exchange. The patient was referred to us for endoscopic removal and treatment of stenosis. A 4F Fogarty catheter was inserted into the right ureter endoscopically and manipulated up alongside the double-J stent. After the balloon was inflated with 0.8 ml of diluted contrast medium, the stent was removed into the urinary bladder. We have found our method to be convenient and safe in the removal of migrated ureteral stent. PMID- 8460591 TI - [A mullerian duct cyst treated by injection of minocycline: a case report]. AB - A 29-year-old male was admitted for the examination of left flank pain. Abdominal ultrasonography revealed a cystic mass beneath the urinary bladder. Computed tomographic scan, magnetic resonance imaging and transrectal ultrasonography showed that this cystic mass was located between the bladder and the prostate. DIP, urethrocystography and seminal vesiculography demonstrated no communication between this mass and the urinary and the seminal tract. From these findings it was diagnosed a mullerian duct cyst. We obtained 15 ml of clear yellowish fluid which contained no sperm by fine needle aspiration under ultrasound guidance and injected minocycline for sclerotherapy. Left flank pain had disappeared and repeated ultrasonography showed a small cystic lesion. However, the size of the cyst was unchanged for six months after discharge. Twenty-five mullerian duct cysts reported in the Japanese literature were reviewed. PMID- 8460592 TI - [Quality of life of the patients with continent urinary reservoir]. AB - To improve the quality of life (QOL) of patients requiring urinary diversion, various surgical techniques including those employing a continent urinary reservoir (CUR), such as Kock pouch or Indiana pouch, and those using the conventional ileal conduit have been advocated. In this study we asked patients who had undergone a CUR operation to complete a questionnaire, consisting of 106 questions relating to the QOL during the disease-free period. A total of 81 questionnaires were sent out, and 60 (74.1%) CUR patients responded. The average age was 61 and the male to female ratio was 49 to 11. The time elapsed from the operation was 42 months. Twenty-nine questions addressed the patients physical condition and on the whole it was kept in good quality. Because they were unwilling to show their stoma, they were reluctant to bathe together with family members. However, 59% of them went to a public bathhouse (common in Japan). Other physical abilities related to exercise were not significantly hampered by this operation. Eighty per-cent of them were not bothered by having a stoma. Twenty four questions were related to social life. The operation had a bad influence in 20-30% of them concerning their interaction with friends and hobbies. Twenty two percent of the patients who had a job prior to the operation stopped working. Only a few patients abandoned travelling. Concerning their sex life (7 questions), males suffered impotence at a very high rate, but only 26% of the patients lost interest in sex. Symptoms related to the operation (41 questions) were mild. Overall, 94% of the patients would choose the same operation again if it were required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460593 TI - Adenomyosis of the seminal vesicle with hematospermia. AB - A 62-year-old man presented in 1987 with hematospermia. No abnormal findings were observed by cystourethroscopy. Ultrasound showed the enlargement of the right seminal vesicle. The right seminal vesicle could not be visualized by seminal vesiculography. Computed tomographic scan revealed a homogeneous mass at the right dorsolateral aspect of the prostate. Surgical exploration was performed. The prostate and bilateral seminal vesicle were resected. Pathological diagnosis was adenomyosis of the right seminal vesicle. PMID- 8460594 TI - [Primary squamous cell carcinoma of the prostate: a case report]. AB - Primary squamous cell carcinoma of the prostate is so rare that only 6 cases have been reported in the Japanese literature. This type of cancer is independent of androgen, and its prognosis seems to be generally poor. The patient was a 76-year old male who was admitted to our hospital with a chief complaint of dysuria. Although the markers for prostatic tumor were within normal ranges, findings in digital examination and imaging suggested prostatic cancer. Because of the marked dysuria, transurethral resection of prostate serving as a biopsy was carried out, and histopathological examination led to a diagnosis of squamous cell carcinoma. Despite 2 courses of chemotherapy with pepleomycin and cis-platinum (CDDP), followed by radiotherapy, the patient died from cancerous cachexia about 9 months after the initial examination. PMID- 8460595 TI - [A case of urinary retention due to ovarian dermoid cyst in a female infant]. AB - The patient was a 20-month-old girl. She visited some pediatric clinic with the chief complaint of voiding difficulty and miction pain from October 5, 1991. Excretory urogram, abdominal ultrasound and computed tomographic scan revealed a retrovesical mass which compressed the urinary bladder antero-superiorly. She was referred to our hospital for further evaluation. Physical examination disclosed a fist-sized tumor in her lower abdomen, which persisted after bladder emptying. Cystoscopy revealed elongation of the urethra and elevation of the bladder base. Tumor markers and endocrine examination were normal. Magnetic resonance imaging at 2 weeks after admission revealed that the retrovesical tumor had been translocated cranial to the bladder. Operation was done on October 29, 1991. The tumor originated from the right ovary and was 6.2 x 5.0 x 5.0cm in size and 60g in weight. The cut surface of the surgical specimen included the fatty tissue and hair, and the pathological diagnosis was an ovarian dermoid cyst. This is the youngest case of ovarian dermoid cyst presenting as urinary retention in the Japanese literature. The mechanism of urinary retention due to infantile gynecological disease is discussed. PMID- 8460596 TI - [A case of benign mesothelioma of the tunica vaginalis testis]. AB - A case of benign mesothelioma of the tunica vaginalis testis is described. A 56 year-old man with no history of asbestos exposure presented with a swelling of the left scrotal content. A physical examination revealed a hydrocele and an induration on the left epididymal head. A cytological examination of the hydrocele fluid demonstrated clusters of mesothelial cells without evidence of malignancy (class III). Left inguinal orchiectomy was performed because a 15 mm papillary pedunculated tumor was seen on the surface of the tunica vaginalis. A microscopic examination showed the papillary and glandular structures composed of cuboidal cells with no cytologic atypia, which were consistent with benign mesothelioma. The patient remains well and free of recurrent disease 10 years after operation. PMID- 8460597 TI - [A case of 46XX male]. AB - A 24-year-old man consulted our hospital with a complaint of male infertility. Semen analysis revealed azoospermia. Endocrinological examination showed elevated serum luteinizing hormone and follicle stimulating hormone levels, and low normal level of serum testosterone. Testicular biopsy disclosed atrophic seminiferous tubules. Abdominal computed tomography revealed no ovaries or uterus. The chromosomal analysis revealed a karyotype of 46XX. This cases was diagnosed as a case of 46XX male. Forty six cases of this syndrome have been cited in the Japanese literature. We discussed the genesis of this syndrome. PMID- 8460598 TI - Biennial survey of physician clinical-nutrition training programs. AB - This is the fourth survey of physician clinical-nutrition training programs. As in previous reports, current fellowship training programs were identified, descriptive information obtained, and program content surveyed. In addition, a questionnaire developed by the American Board of Nutrition Committee on Fellowship Training Programs was used to determine the degree of emphasis given to content in the areas of basic nutrition science, clinical applications, and research training. Among the 38 programs identified, uniform ratings of importance were found in all major topic areas. There was also uniformity in most subtopics, with minor exceptions. As expected, in the area of nutrition in the life cycle, pediatric training programs emphasized infancy and childhood whereas medical-surgical programs emphasized adulthood and aging. Alcoholism was emphasized in medical-surgical training programs whereas cystic fibrosis and inborn errors of metabolism were emphasized in pediatric programs. Nutrition in burn patients received minor emphasis in all programs. The overall uniformity of curricular content in training programs confirms the contention that clinical nutrition has a defined clinical scope and should be considered for establishment as a recognized subspecialty in American medicine. PMID- 8460599 TI - Adipose tissue distribution measured by magnetic resonance imaging in obese women. AB - This study had two objectives: 1) to establish magnetic resonance imaging (MRI) as a tool for measuring subcutaneous and visceral adipose tissue (AT) distribution in obese women, and 2) to assess the relationship between selected anthropometric variables and MRI-measured AT. Fifteen healthy obese women aged 35.0 +/- 9.8 y (mean +/- SD) with a body mass index of 36.4 +/- 7.1 and a waist to-hip ratio of 0.91 +/- 0.05 participated in the study. The mean difference for repeated measures of subcutaneous and visceral AT area at L4-L5 was 1.1% (P = 0.15) and 5.5% (P = 0.14), respectively. Large interindividual differences were observed for total (30.2-81.7 L), subcutaneous (27.1-76.8 L), and visceral AT volume (0.9-5.5 L). Subcutaneous and visceral AT represented 92.3% and 6.3% of the total AT volume, respectively. Hip (r2 = 0.96) and waist (r2 = 0.88) circumferences were significant predictors of subcutaneous AT volume. The combination of body weight, age, and height explained 89% of the variance in visceral AT volume. These results demonstrate that MRI provides reliable measures of subcutaneous and visceral AT distribution in obese women. PMID- 8460600 TI - Circadian variation of diet-induced thermogenesis. AB - The objective of this study was to assess a circadian variation of diet-induced thermogenesis (DIT) that could favor weight gain among night workers used to eating a night time snack. Nine young men were given the same mean at 0900, 1700, or 0100. Energy expenditure was measured by indirect calorimetry 1 h before and during the 6 h after the snack. DIT was calculated as the 3 h of energy expenditure above basal metabolic rate. Morning DIT was significantly higher than afternoon DIT (P = 0.04) and night DIT (P = 0.002). Afternoon DIT was higher than night DIT (P = 0.06). We conclude that the time when a meal is consumed affects the thermogenic response and must be considered in the energy balance. PMID- 8460601 TI - Meal-induced thermogenesis in lean and obese prepubertal children. AB - The resting metabolic rate (RMR) and the thermic effect of a meal (TEM) were measured in a group of 16 prepubertal (8.8 +/- 0.3 y) obese children (43.6 +/- 9.2 kg) and compared with a group of 10 age-matched (8.6 +/- 0.4 y), normal weight children (31.0 +/- 6.0 kg). The RMR was higher in the obese than in the control children (4971 +/- 485 vs 4519 +/- 326 kJ/d, P < 0.05); after the RMR was adjusted for the effect of fat-free mass (FFM) the values were not significantly different (4887 +/- 389 vs 4686 +/- 389 kJ/d). The thermic response to a liquid mixed meal, expressed as a percentage of the energy content of the meal, was significantly lower in obese than in control children (4.4 +/- 1.2% vs 5.9 +/- 1.7%, P < 0.05). The blunted TEM shown by the obese children could favor weight gain and suggests that the defect in thermogenesis reported in certain obese adults may have already originated early in life. PMID- 8460602 TI - Food preferences, body weight, and platelet-poor plasma serotonin and catecholamines. AB - The possible relationship between body weight, food preferences, and plasma neurotransmitters was investigated in 96 healthy volunteers. The volunteers were divided into groups according to sex, body mass index, and food preferences. In all groups fasting platelet-poor plasma (PPP) norepinephrine and serotonin (5-HT) were examined. PPP-5-HT was low in obese individuals (mean +/- SD: 51.7 +/- 34.6 nmol/L) in comparison with lean individuals (94.31 +/- 85.2 nmol/L; P < 0.01), in lean male carbohydrate cravers (22.7 +/- 16.4 nmol/L) in comparison with protein cravers (132.9 +/- 80.6 nmol/L; P < 0.005) and noncravers (64.7 +/- 51.7 nmol/L; P < 0.05), and in obese male carbohydrate cravers (34 +/- 22.7 nmol/L) in comparison with obese male protein cravers (98.8 +/- 28.4 nmol/L; P < 0.001). In conclusion, PPP-5-HT might be seen as a peripheral indicator of processes linked with food consumption and food preferences. PMID- 8460603 TI - Long-term effects of weight reduction on serum lipids and plasma insulin in obese children. AB - The long-term metabolic effects of weight reduction on serum lipids and plasma insulin were evaluated in 32 obese children with a mean (+/- SD) relative weight of 160.9 +/- 20.1% before and after active treatment for 1 y and after observation for another 4 y. The obese subjects had higher serum triglyceride and plasma insulin concentrations initially but lower high-density-lipoprotein (HDL) cholesterol concentrations and a lower ratio of HDL cholesterol to total cholesterol (TC) than 29 normal-weight children. There was a decrease of 15.8% in relative weight over the first year with a parallel decrease in serum triglyceride and plasma insulin, whereas HDL cholesterol and the ratio of HDL cholesterol to TC increased (P < 0.001). These changes remained stable over the second year. At 5 y the obese subjects still had a reduced weight (12.8% lower than initially) and higher HDL cholesterol. These results indicate that weight reduction in obese children is associated with a change in serum lipids toward normal and reduced peripheral hyperinsulinemia. PMID- 8460604 TI - Longitudinal assessment of energy expenditure in pregnancy by the doubly labeled water method. AB - Twelve women were studied before pregnancy and at 6-wk intervals from 6 to 36 wk gestation. Total energy expenditure (TEE) by the doubly labeled water method, basal metabolic rate (BMR), energy intake, and body composition were assessed on each occasion. There was substantial interindividual variation in the response to pregnancy. Mean total energy costs were as follows: delta BMR 112 +/- 104 MJ (range -53 to 273), delta TEE 243 +/- 279 MJ (range -61 to 869 MJ), and fat deposition 132 +/- 127 MJ (range -99 to 280 MJ). The mean total cost of pregnancy (cumulative TEE above baseline+energy deposited as fat and as products of conception) was 418 +/- 348 MJ (range 34-1192 MJ). This was much higher than current recommendations for incremental energy intakes. Self-recorded incremental intakes (208 +/- 272 MJ) seriously underestimated the additional costs. The variability in response emphasizes the problems in making prescriptive recommendations for individual women, because there is no way of predicting metabolic or behavioral responses to pregnancy. PMID- 8460606 TI - Energy expenditure in lactating women: a comparison of doubly labeled water and heart-rate-monitoring methods. AB - Estimates of total daily energy expenditure (TDEE) by heart-rate (HR) monitoring were compared with those made by the doubly labeled water (DLW) method in nine exclusively breast-feeding women. Subjects recorded HR and dietary intake daily during the 8-d, isotope-measurement period. Milk energy output was determined by 3-d test weighing and analysis of 24-h milk samples. Total energy output (milk energy and TDEE) averaged 12.36 +/- 1.03 MJ/d with DLW compared with 11.74 +/- 1.3 MJ/d with HR monitoring, a 5.8% difference (NS). Individual differences ranged from -27.1% to +17.6%. The high water turnover and relatively low level of activity during lactation made the slopes of deuterium and 18O disappearance more similar, resulting in increased error in estimates of TDEE by DLW. Therefore, the DLW method may not be appropriate for use in lactating women. There are considerable individual deviations in estimating TDEE by HR monitoring, but it is satisfactory for estimating TDEE of groups. PMID- 8460605 TI - Nutritional efficacy of a fortified weaning rusk in a rural area near Beijing. AB - A micronutrient-fortified rusk for weanling children was tested in a rural area near Beijing. Two hundred twenty-six children aged 6-13 mo were randomly assigned by village to either a micronutrient-fortified or an unfortified rusk, daily for 3 mo. The fortified rusk contained extra zinc; iron; calcium; vitamins A, D, and B-12; thiamin, riboflavin, niacin, and folic acid. Infants receiving the fortified rusk exhibited no decline in hemoglobin concentrations during the study whereas those receiving the unfortified rusk exhibited a significant decline. Improvements were also seen in erythrocyte porphyrin, plasma vitamin A, and riboflavin status, but these improvements were seen in both of the groups. Micronutrient fortification was probably beneficial for iron status and the fortified rusk promises to be an effective vehicle for supplementation. PMID- 8460607 TI - Breast milk chromium and its association with chromium intake, chromium excretion, and serum chromium. AB - Chromium metabolism of lactating women was evaluated by measuring diet, breast milk, urine, and serum chromium in 17 subjects 60 d postpartum. Breast milk chromium concentration was similar for the 3 d of collection with a mean +/- SE concentration of 3.54 +/- 0.40 nmol/L (0.18 ng/mL). Dietary intake and urinary chromium values were also similar for each of the 3 collection days. Total chromium intake of lactating mothers (0.79 +/- 0.08 mumol/d) was greater than that of reference female subjects (0.48 +/- 0.02). There was a significant correlation (r = 0.84) between serum chromium and urinary chromium excretion. If a breast milk volume of 715 mL is assumed, chromium intake of exclusively breast fed infants is < 2% of the estimated safe and adequate daily intake of 10 micrograms. In summary, breast milk chromium content is independent of dietary chromium intake and serum or urinary chromium values. Chromium intake also did not correlate with serum or urine chromium but there was a significant relationship between serum and urinary chromium concentrations. PMID- 8460608 TI - Different clearance of intravenously administered olive oil and soybean-oil emulsions: role of hepatic lipase. AB - The elimination of two intravenously administered fat emulsions consisting of either 20% (wt:vol) soybean oil or 17% olive oil plus 3% soybean oil was studied in six normolipidemic young men according to a randomized crossover protocol. Slower elimination was found with the olive oil emulsion. A significantly lower maximal removal capacity (K1) and fractional catabolic rate (K2) were measured with olive oil emulsion (P < 0.05). Removal of olive oil emulsion was inversely related to hepatic lipase activity (r = -0.85; P < 0.05). Removal of soybean-oil emulsion was related to the initial plasma triglyceride concentration (r = -0.84; P < 0.05) but not to lipolytic activity. In vivo apolipoprotein C-II binding was similar for both emulsions. Therefore, hepatic lipase activity is more important in the elimination of olive oil emulsions than soybean-oil emulsions. The faster elimination of soybean-oil emulsions suggests an additional elimination pathway, such as the reticuloendothelial system. PMID- 8460609 TI - Validation of an in vitro assay for predicting the amount of starch that escapes digestion in the small intestine of humans. AB - The aim of the present study was to validate an in vitro assay for quantifying resistant starch (RS) in foods against an in vivo model. The amount of starch escaping digestion in the small intestine of ileostomates was compared with that observed by using the in vitro assay. Subjects with ileostomies were fed five foods containing different types and amounts of RS (baked beans, pearl barley, cornflakes, and whole and ground rice). The total amount of starch escaping digestion and recovered in the effluent (ranging from 5.7% in baked beans to 0.7% in ground rice) was compared with results obtained by using the in vitro assay with an incubation time of 6 h. The assay was found to be a good qualitative predictor (r = 0.90, P < 0.05), but a poor quantitative predictor of RS amounts. Increasing the duration of incubation with alpha-amylase and amyloglucosidase to 15 h resulted in a very close agreement between results from the in vitro technique and the in vivo model. These data indicate that for a variety of foods the in vitro assay produced an excellent estimate of starch escaping digestion in the small intestine of humans. PMID- 8460610 TI - Problems with estimating vitamin C intakes. AB - The vitamin C content of foods was examined from two national databases and new values were obtained by HPLC. HPLC values were lower in four of the five highest vitamin C contributors to the US diet (orange juice, grapefruit, tomatoes and tomato juice, and potatoes), as well as in broccoli, red peppers, and cooked collard and mustard greens, compared with values from the other databases. When HPLC values were substituted in the Health Habits and History Questionnaire, the resulting estimates of dietary intake of vitamin C in two studies were lower. Despite these lower estimates of absolute intake, in one study the correlation between dietary vitamin C and plasma ascorbic acid was similar. In conclusion, the accuracy of the vitamin C content of foods is important for estimating the absolute amount of vitamin C intake in the population but may not change the ranking of people in epidemiological studies. PMID- 8460611 TI - Seasonal variation of serum concentrations of beta-carotene and alpha-tocopherol. AB - We studied the seasonal variation in serum concentrations of beta-carotene and alpha-tocopherol (HPLC) in 17,247 Finnish men who smoked. Month of blood sampling was a statistically significant determinant of serum concentration of beta carotene in a regression model including age, body mass index, alcohol and fat intakes, total serum cholesterol, and daily cigarettes as covariates. The serum concentrations were lowest in April-June and highest in October-November. The 1.5 fold increase in the serum concentration of beta-carotene during the fall reflects the seasonality of dietary sources of carotenoids in Finland. The serum concentrations of alpha-tocopherol demonstrated no seasonal variation but remained close to 27.6 mumol/L throughout the year. The results indicate that the seasonal variation of serum concentrations of beta-carotene should be taken into account in long-term studies in which comparison of groups or individuals is based on serum concentrations. PMID- 8460612 TI - Homeostatic control of zinc metabolism in men: zinc excretion and balance in men fed diets low in zinc. AB - Zinc metabolism was studied in 11 men. The study began with 28-d equilibration when dietary zinc was 159 mumol/d (X), followed by 35-d periods when the diet contained 21.9 (I), 37.5 (II), 51.6 (III), or 67.8 (IV) mumol Zn/d in random order, and ended with 35 d with X. The diet was conventional foods and egg white protein. Zinc balance, including surface and semen losses, was zero only during I. Semen zinc was unaffected by diet. Plasma zinc dropped to 0.44 and 0.49 mumol/L in two subjects during I and was significantly decreased during I compared with X (P < 0.0002). Urinary zinc declined with decreasing zinc intake. A combination of urinary and plasma zinc criteria from Baer and King (Am J Clin Nutr 1984; 39:556-70) could be used to distinguish stages of zinc deficiency. By these criteria, no subjects were deficient during IV, one was marginally deficient during III, three were marginally deficient during II, and seven were deficient during I. PMID- 8460613 TI - A physiological amount of zinc supplementation: effects on nutritional, lipid, and thymic status in an elderly population. AB - Forty-four institutionalized elderly subjects with body mass indexes (BMI) of either > or = 24 or < or = 21 participated in a 16-wk crossover study designed to determine the effects of low-dose zinc supplementation [306 mumol (20 mg)/d] on food intake, anthropometry, and biochemical and immunological indexes. Initial serum zinc concentrations were low in both groups and increased by approximately 20% after zinc supplementation. Zinc supplementation allowed a partial but significant restoration of serum thymulin activity and improved nutritional status (food intake and serum albumin and transthyretin concentrations) but had no effect on anthropometric indexes or serum apolipoproteins, except apolipoprotein CII and apolipoprotein CIII. After zinc supplementation, serum copper concentration decreased but there was no change in the ratio of low density-lipoprotein cholesterol to high-density-lipoprotein cholesterol. Low-dose zinc supplementation allows restoration, at least partially, of nutritional and thymic status without the known disadvantages of high doses of zinc. PMID- 8460614 TI - Lipoprotein abnormalities associated with cholesteryl ester transfer activity in cystic fibrosis patients: the role of essential fatty acid deficiency. AB - The purpose of this study was to elucidate the roles of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in the lipoprotein derangement of cystic fibrosis (CF) patients with respect to their essential fatty acid (EFA) status. Triglyceride enrichment and cholesteryl ester (CE) depletion were observed in the lipoproteins of 22 CF patients. The abnormal chemical composition was more severe in 12 EFA-deficient (EFAD) than in 10 EFA sufficient (EFAS) patients. Expressed in nmol.L-1.h-1, LCAT activity was higher (P < 0.05) in both EFAS (mean +/- SE, 92.7 +/- 1.9) and EFAD (108.8 +/- 3.0) patients than in control subjects (65.2 +/- 0.9). An equal CE transfer was recorded in the lipoprotein-deficient serum, as a source of CETP activity, in all groups studied by using normal exogenous low-density lipoprotein (LDL) and high density lipoprotein (HDL). However, in contrast to the maximal amount of CE transferred from endogenous HDL to endogenous apolipoprotein B (apo B) in control subjects, a reduction in CETP activity was seen in CF patients and more pronounced in the EFAD group. These findings indicate that impaired lipoprotein composition may have marked effects on the transfer of CE between HDL and apo B in EFAD CF patients. PMID- 8460615 TI - Relationships among nutritional status and skeletal and respiratory muscle function in cystic fibrosis: does early dietary supplementation make a difference? AB - Relationships among nutritional status and skeletal and respiratory muscle function were examined in 16 children with cystic fibrosis (CF) and mild lung disease (FEV1 95 +/- 16% predicted). Subjects were randomly assigned to receive (or not) noninvasive nutritional supplementation at 25% of normal energy recommendations for 6 mo. Skeletal muscle strength and power were similar to those of healthy children as were respiratory muscle strength and endurance. Stepwise-regression analysis indicated that changes in skeletal muscle strength and energy intake correlated significantly with growth [weight (kg) = 1.90 - 0.60 (Tanner Stage) + 0.49 (maximum voluntary strength (Nm) + 0.03 (energy intake, % RNI), r = 0.76, P < 0.05], though body composition, protein biochemistry, muscle power, respiratory muscle strength, and use of dietary supplements did not. Thus, changes in skeletal muscle strength may be a functional index of changes in nutritional status in CF. Dietary supplementation per se was not associated with functional improvement. PMID- 8460616 TI - Growth and body composition in children infected with the human immunodeficiency virus-1. AB - Anthropometric data were collected on 89 children born to human immunodeficiency virus (HIV)-infected women (37 who seroreverted and 52 who were HIV-infected). The main outcomes included birth weight, gestational age, weight, height, arm muscle circumference (AMC), and triceps skinfold thickness (TSF). Gestational age and birth weight were not different between the two groups. The earliest anthropometric evaluation on seroreverted children (age 19 mo) when compared with HIV-infected children (age 21 mo) revealed that weight and weight-for-height percentiles were significantly different (51% vs 33% and 66% vs 48%, respectively). Height and TSF percentiles were not different, although AMC percentiles were lower in infected children (64% vs 43%). In follow-up evaluations, the weight differences between infected and control children did not change. We conclude that HIV does not affect birth weight, but postnatal events result in altered weight gain in HIV-infected children. Lean body mass is lower than in an HIV-negative comparison group at early stages of HIV infection. PMID- 8460617 TI - Classification of Peruvian infants by using reference growth data. PMID- 8460618 TI - Diabetes and energy intake. PMID- 8460619 TI - Vitamin C inhibition of N-nitroso compound formation. PMID- 8460620 TI - Perimenopausal increase in serum cholesterol: a 10-year longitudinal study. AB - The relative contribution of menopause to the age-related increase in serum total cholesterol concentration in women is not exactly known. Cross-sectional studies suggest a considerable contribution of menopause, whereas in short-term longitudinal studies, only a small increase was observed around menopause. In a 10-year follow-up study (1979-1989), serum total cholesterol concentration and dietary intake were measured annually in 167 healthy perimenopausal women (initially aged 49-56 years) who lived in the mixed rural/industrial community of Ede, the Netherlands. The longitudinal design enabled us to study the "natural course" of serum total cholesterol concentration and the influence of dietary fat intake during and after cessation of ovulation. For data analysis, three menopausal cohorts were created based on years relative to menopause: 2 years before ("perimenopausal"), 2 years after ("early postmenopausal"), and 6 years after ("late postmenopausal"). In each cohort, the analysis was conducted on data from 4 years of follow-up. The results show that from 2 years before to 6 years after menopause, serum total cholesterol concentration increased on average by at least 1.1 mmol/liter (19%). Thereafter, only a minor increase was observed. The rise was significantly lower in women who increased their intake of polyunsaturated fatty acids as compared with women who reduced their intake during that period. It is concluded that cessation of ovulation appears to be associated with a major increase of 19% in serum total cholesterol concentration during an 8-year period around menopause. This increase may be reduced by increasing the intake of polyunsaturated fatty acids. PMID- 8460621 TI - Diet and endometrial cancer: a case-control study. AB - A case-control study of 168 cases with endometrial cancer and 334 controls was conducted in Birmingham, Alabama, between June 1985 and December 1988. Cases were identified at the University of Alabama Hospital and in a private practice; controls were selected from among women who attended the University optometry clinic. A food frequency questionnaire that evaluated the intake of 55 nutrients and 116 foods was obtained for 103 cases and 236 controls. Logistic regression was used to evaluate the effect of diet on endometrial cancer after adjustment for total calories, age, race, education, obesity, smoking status, age at menarche, number of pregnancies, age at menopause, diabetes, hypertension, and use of exogenous estrogens. High intake of certain micronutrients was associated with a decreased risk of endometrial cancer: the odds ratio for subjects in the upper tertile versus those in the lower tertile was 0.4 for both carotene and nitrate (95% confidence interval (CI) 0.2-0.8 and 0.2-0.9, respectively). There also was an inverse association between endometrial cancer and protein consumption (trend test; p = 0.002), and a moderate direct association with cholesterol intake (OR = 1.9, 95% CI 0.9-3.7) when terms for both these macronutrients were included in a logistic model. Total intake of animal and vegetable fat were not associated with endometrial cancer. More frequent consumption of several vegetables and certain dairy products was associated with a statistically significant decreased risk of endometrial cancer. These results suggest that diet plays an important role in the etiology of endometrial cancer. PMID- 8460622 TI - Calcium, magnesium, and free fatty acids in the formation of gallstones: a nested case-control study. AB - In a nested case-control study, calcium status was assessed by measurements of serum total calcium, magnesium, phosphate, ionized calcium, parathyroid hormone, albumin, total CO2 (bicarbonate), and free fatty acids in relation to gallstone formation. The subjects were recruited from a cohort study (n = 4,581) on the epidemiology of gallstones in Denmark. The cohort was examined with ultrasonography twice, in 1983 and 1988; 63 subjects developed gallstones, and among those who did not, 122 were randomly selected as controls. Subjects with gallstones had significantly increased serum concentrations of total calcium, magnesium, and bicarbonate as compared with normal subjects. The difference was only observed in women. Age, body mass index, alcohol consumption, and smoking did not influence the results when included as covariables in a logistic regression analysis. Multivariate analysis showed increased concentrations of magnesium, bicarbonate, and parathyroid hormone to be significantly associated with gallstone disease in women. No significant association was observed between gallstone disease and serum variables in men. PMID- 8460623 TI - Copper in human mammary carcinogenesis: a case-cohort study. AB - In 1968-1975, a cohort of 5,100 ostensibly healthy women was established on the island of Guernsey, England, for investigation of the influence of hormonal factors on breast cancer. At the women's entry into the study, blood samples were drawn from each participant, and each woman completed a questionnaire that provided information on established risk indicators in human mammary carcinogenesis. Plasma copper levels were measured in 46 breast cancer cases diagnosed an average of 11 years (standard deviation (SD), 4) after entry into the study cohort and in an age-stratified random sample of 138 women drawn from the total initial cohort at risk. Plasma copper levels were 1.31 mg/liter (SD, 0.37) in the cases and 1.26 mg/liter (SD, 0.36) in the controls; the 95% confidence interval for the overall difference was -0.07 to 0.17. A U-shaped relation between premorbid plasma copper levels and the risk of developing breast cancer was seen. Adjusted odds ratios for breast cancer were 1.8, 1.0, 1.6, and 3.2, respectively, in the four quartiles of the copper distribution. No major changes in the risk estimates were observed when statistical evaluation was restricted to cases diagnosed more than 10 years after collection of blood samples. PMID- 8460624 TI - Maternal risk factors for congenital syphilis: a case-control study. AB - This study estimated the strength of association between maternal cocaine use and congenital syphilis after adjustment for other factors, especially the use of prenatal care. The authors reviewed medical chart and laboratory data for 75 liveborn infants treated for congenital syphilis at Harlem Hospital Center (New York City) in 1987, 150 matched control infants, and their mothers. Cocaine use was determined from universal maternal medical histories and infant toxicology screenings, and the sensitivity of each method of ascertainment was evaluated. With the use of either maternal history or positive infant urine toxicology as evidence of cocaine use, 66.2% (49/74) of case infants versus 16.1% (24/149) of control infants were judged to have been exposed to cocaine in utero (odds ratio (OR) = 9.1, 95% confidence interval (Cl) 4.7-29.2). However, in multiple logistic regression, lack of prenatal care was the single variable with the highest adjusted odds ratio (adjusted OR = 11.0, 95% Cl 1.3-93.1); maternal cocaine use had the second-highest adjusted odds ratio (adjusted OR = 4.9, 95% Cl 1.8-13.0). Thus, despite the emergence of maternal cocaine use as a new risk factor, underutilization of prenatal care remains the strongest predictor of congenital syphilis. PMID- 8460625 TI - Assessment of blood lead levels in children living in a historic mining and smelting community. AB - Lead poisoning in childhood is an important public health problem, and thus, it is important to determine how children are exposed to lead. In 1987, the authors conducted an exposure assessment and blood lead screening for children aged 6-71 months living in Leadville, Colorado. High levels of lead had been found in the soil as a result of both past mining and smelting activities and natural mineralization. Blood was collected from each child for lead analysis, and behavioral characteristics were identified through an interview with a parent or guardian. Three sources of exposure to lead were associated with blood lead levels: lead in a core sample taken from the backyard of the family's home, lead brought home on the clothes of a miner, and lead from soldering in the home. Two pathways of exposure were associated with blood lead levels: the child swallowing things other than food, and taking food or a bottle outside to play. Multivariate regression using these variables found effect modification by age. For children aged 6-36 months, only sources of exposure were independent predictors of blood lead levels, while in children aged 37-71 months, a pathway of exposure in addition to sources of exposure independently predicted blood lead levels. PMID- 8460626 TI - Association of education with reported age of onset and severity of Alzheimer's disease at presentation: implications for the use of clinical samples. AB - Clinical samples are commonly used to attempt to infer factors that are etiologically important in Alzheimer's disease. Use of clinical samples for these purposes is valid if and only if detection of Alzheimer's disease is unbiased with respect to the factors being studied. The issue of how education influences detection of Alzheimer's disease is controversial. The purpose of the present investigation was to shed light on the role of education in the detection of symptoms of Alzheimer's disease. To do so, we examined the association of education with age of symptom onset, severity of disease at diagnosis, and time from symptom onset until diagnosis in a large clinical sample of Alzheimer's disease patients from throughout California. The diagnoses of the 1,658 cases in the sample were made in 1985-1990. Age of onset was defined as the age at which symptoms first appeared, according to family members. Severity of dementia was measured with Blessed-Roth Dementia Rating Scale scores. The reported age at symptom onset was later in those with less education (p < 0.0001). However, decreasing education was associated with greater severity of disease at presentation (p < 0.008), suggesting that a lower educational level may lead to later detection of Alzheimer's disease and referral to clinical centers at a later stage of disease. This implies that using clinical samples of Alzheimer's disease patients to study factors correlated with age at onset may lead to biased conclusions, if these factors are also associated with education. PMID- 8460627 TI - A novel approach to the characterization of cumulative exposure for the study of chronic occupational disease. AB - Inappropriate parameterization of an exposure metric for the study of occupational and environmental hazards may lead to significant misclassification and biased results. A model for identification of an optimal expression for cumulative exposure that includes exponentiated terms for concentration and time was developed. When the values of the exponents are allowed to vary, an optimal expression for cumulative exposure may be identified. The approach has advantages for the study of chronic hazards, in that it is flexible, limits the number of assumptions, and incorporates many of the models generally suggested in the literature. In addition, the model results may be interpreted to suggest particular pathophysiologic mechanisms. The model was implemented with data from a previously studied cohort of underground coal miners, and the associations between the exposure metric and measures of obstructive lung disease were identified. The results demonstrated that the exposure metric can improve the association of dust exposure histories with various outcomes over the usual measure of cumulative exposure. However, in the particular data set used, the overall predictive power of alternative models was similar and the interpretability of the results was limited. PMID- 8460628 TI - Comparison of three methods of estimating odds ratios from a job exposure matrix in occupational case-control studies. AB - A job exposure matrix consists of jobs on one axis and substances on the other, with the matrix elements describing the likelihood of an individual's exposure to a substance in a given job. This can be used in case-control studies to infer exposures of subjects whose jobs are known. The simplest form of job exposure matrix contains binary entries, but it is also possible to envisage continuous variables describing the probability of exposure in the job (probabilistic matrix). In such a case, the user has various options for transforming and analyzing the data, including the following: 1) transform to binary variables and analyze as conventional binary exposure variables; 2) leave as continuous variables and analyze using logistic regression; 3) leave as continuous variables and analyze using a linear model. Simulations were carried out to compare the ability of the three methods to estimate odds ratios under 36 experimental conditions. The linear model produced unbiased estimates, the logistic model produced somewhat biased estimates at high odds ratios, and the transformation to a binary variable produced systematically low estimates in most experimental circumstances. With the linear and logistic models, the odds ratio estimators had similar precision when the bias of the latter was not too great. The authors conclude that the linear model permits optimal use of a probabilistic matrix in an epidemiologic study and hope that these results will encourage the development of job exposure matrices containing probabilities rather than dichotomies. PMID- 8460629 TI - Re: "Risk factors for mortality from all causes and from coronary heart disease among persons with diabetes: findings from the National Health and Nutrition Survey I Epidemiologic Follow-up Study". PMID- 8460630 TI - Re: "A simple, valid step test for estimating maximal oxygen uptake in epidemiologic studies". PMID- 8460631 TI - Aging, healing, and the metabolism of telomeres. PMID- 8460632 TI - Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. AB - The telomere hypothesis of cellular aging proposes that loss of telomeric DNA (TTAGGG) from human chromosomes may ultimately cause cell-cycle exit during replicative senescence. Since lymphocytes have a limited replicative capacity and since blood cells were previously shown to lose telomeric DNA during aging in vivo, we wished to determine: (a) whether accelerated telomere loss is associated with the premature immunosenescence of lymphocytes in individuals with Down syndrome (DS) and (b) whether telomeric DNA is also lost during aging of lymphocytes in vitro. To investigate the effects of aging and trisomy 21 on telomere loss in vivo, genomic DNA was isolated from peripheral blood lymphocytes of 140 individuals (age 0-107 years), including 21 DS patients (age 0-45 years). Digestion with restriction enzymes HinfI and RsaI generated terminal restriction fragments (TRFs), which were detected by Southern analysis using a telomere specific probe (32P-(C3TA2)3). The rate of telomere loss was calculated from the decrease in mean TRF length, as a function of donor age. DS patients showed a significantly higher rate of telomere loss with donor age (133 +/- 15 bp/year) compared with age-matched controls (41 +/- 7.7 bp/year) (P < .0005), suggesting that accelerated telomere loss is a biomarker of premature immunosenescence of DS patients and that it may play a role in this process. Telomere loss during aging in vitro was calculated for lymphocytes from four normal individuals, grown in culture for 10-30 population doublings. The rate of telomere loss was approximately 120 bp/cell doubling, comparable to that seen in other somatic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460633 TI - De novo truncation of chromosome 16p and healing with (TTAGGG)n in the alpha thalassemia/mental retardation syndrome (ATR-16). AB - We have previously described a series of patients in whom the deletion of 1-2 megabases (Mb) of DNA from the tip of the short arm of chromosome 16 (band 16p13.3) is associated with alpha-thalassemia/mental retardation syndrome (ATR 16). We now show that one of these patients has a de novo truncation of the terminal 2 Mb of chromosome 16p and that telomeric sequence (TTAGGG)n has been added at the site of breakage. This suggests that the chromosomal break, which is paternal in origin and which probably arose at meiosis, has been stabilized in vivo by the direct addition of the telomeric sequence. Sequence comparisons of this breakpoint with that of a previously described chromosomal truncation (alpha alpha)TI do not reveal extensive sequence homology. However, both breakpoints show minimal complementarity (3-4 bp) to the proposed RNA template of human telomerase at the site at which telomere repeats have been added. Unlike previously characterized individuals with ATR-16, the clinical features of this patient appear to be solely due to monosomy for the terminal portion of 16p13.3. The identification of further patients with "pure" monosomy for the tip of chromosome 16p will be important for defining the loci contributing to the phenotype of this syndrome. PMID- 8460634 TI - Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. AB - Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance; in such families the disease often occurs in association with ovarian cancer. Previous genetic linkage studies have established that in some such families disease occurrence is linked to markers on chromosome 17q. This paper reports the results of a collaborative linkage study involving 214 breast cancer families, including 57 breast-ovarian cancer families; this represents almost all the known families with 17q linkage data. Six markers on 17q, spanning approximately 30 cM, were typed in the families. The aims of the study were to define more precisely the localization of the disease gene, the extent of genetic heterogeneity and the characteristics of linked families and to estimate the penetrance of the 17q gene. Under the assumption of no genetic heterogeneity, the strongest linkage evidence was obtained with D17S588 (maximum LOD score [Zmax] = 21.68 at female recombination fraction [theta f] = .13) and D17S579 (Zmax = 13.02 at theta f = .16). Multipoint linkage analysis allowing for genetic heterogeneity provided evidence that the predisposing gene lies between the markers D17S588 and D17S250, an interval whose genetic length is estimated to be 8.3 cM in males and 18.0 cM in females. This position was supported over other intervals by odds of 66:1. The location of the gene with respect to D17S579 could not be determined unequivocally. Under the genetic model used in the analysis, the best estimate of the proportion of linked breast-ovarian cancer families was 1.0 (lower LOD-1 limit 0.79). In contrast, there was significant evidence of genetic heterogeneity among the families without ovarian cancer, with an estimated 45% being linked. These results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist. By examining the fit of the linkage data to different penetrance functions, the cumulative risk associated with the 17q gene was estimated to be 59% by age 50 years and 82% by age 70 years. The corresponding estimates for the breast-ovary families were 67% and 76%, and those for the families without ovarian cancer were 49% and 90%; these penetrance functions did not differ significantly from one another. PMID- 8460635 TI - A somatic cell hybrid map of the long arm of human chromosome 17, containing the familial breast cancer locus (BRCA1). AB - We describe a detailed somatic cell hybrid map of human chromosome 17q11.2-q23, containing the familial breast and ovarian cancer locus (BRCA1) and highly informative closely linked markers. An X-irradiation panel of 38 hamster/human and mouse/human hybrids with fragments of chromosome 17 was generated and characterized with 22 STS markers from this chromosome. A detailed map of 61 probes onto chromosome 17q, subdividing the chromosome arm into 25 regions, was done by using a panel of hybrids with well-defined breakpoints and nine chromosome-mediated gene transfectants. Our localization of RARA, TOP2, EDH17B1 and 2, and possibly WNT3, between THRA1 and D17S181, two markers known to flank BRCA1, suggests that any of these is a potential candidate for the BRCA1 locus. The marker D17S579 (Mfd188), which is believed to be very close to BRCA1, maps closest to the EDH17B genes. PMID- 8460636 TI - Linkage analysis of chromosome 17q markers and breast-ovarian cancer in Icelandic families, and possible relationship to prostatic cancer. AB - Seven families, selected for breast cancer segregation, have been analyzed for chromosome 17q12-q23 linkage to breast and ovarian cancer. In two of them, linkage is seen with most markers tested, increasing toward the most proximal region, but without informative recombinations above NM23. In the remaining families, no linkage is observed. Families with 17q linkage are not easily distinguished by clinical characteristics such as early onset (mean age at diagnosis < or = 45 years) or organs involved. In fact, the family with the highest lod scores (> or = 2.3) belongs to the "later onset" (> 45 years) category of families. Interestingly, prostatic cancer is the most frequent malignancy, after breast cancer, in the families that we studied (13 cases total, all metastasizing) and is especially prevalent in males presumed to carry the trait. Of 16 paternal carriers, 7 (44%) had developed prostatic cancer. Haplotype analysis in families with 17q linkage reveals two further prostatic cases as potential carriers. We propose that breast cancer genes may predispose to prostatic cancer in male carriers. PMID- 8460637 TI - THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21. AB - In order to pinpoint the locale of the gene for early-onset familial breast and ovarian cancer (BRCA1), polymorphisms were developed within the locus for thyroid hormone receptor alpha (THRA1) and for several anonymous sequences at chromosome 17q12-q21. The THRA1 polymorphism is a dinucleotide repeat with 10 alleles and heterozygosity.79. Gene mapping in extended families with inherited, early-onset breast and ovarian cancer indicates that BRCA1 is distal to THRA1 and proximal to D17S183 (SCG43), an interval of < 4 cM. This locale excludes HER2, THRA1, WNT3, HOX2, NGFR, PHB, COLIA1, NME1, and NME2 as candidates for BRCA1 but does not exclude RARA or EDH17B. Resolving the remaining recombination events in these families by new polymorphisms in the THRA1-D17S183 interval will facilitate positional cloning of the breast-ovarian cancer gene on chromosome 17q12-q21. PMID- 8460638 TI - Linkage of a major breast cancer gene to chromosome 17q12-21: results from 15 Edinburgh families. AB - DNA from members of 15 pedigrees each containing between three and eight cases of breast cancer have been collected from southeastern Scotland. Polymorphic markers on chromosome 17q were screened to locate a putative breast cancer gene by using DNA from relevant individuals within these families. Pairwise LOD scores were calculated for markers D17S74, NM23, D17S588, and D17S579. The maximal summated LOD for the 15 families was 5.44 at theta = .034, when D17S588 (42D6) was used. In these breast cancer families, a subset which did not give evidence for linkage to this region could be identified. PMID- 8460639 TI - A breast-ovarian cancer susceptibility gene maps to chromosome 17q21. AB - Nineteen North American Caucasian families that contain a minimum of four confirmed cases of breast or ovarian cancer have been studied. Four polymorphisms (cLB17.1, D17S579, D17S588, and D17S74), which span a region of approximately 15 cM on chromosome 17q12, were typed. Our data confirm the location of a dominant gene conferring susceptibility to breast and ovarian cancer (maximum lod = 9.78) and suggest that the breast-ovarian cancer syndrome is genetically heterogeneous. Two recombinants in one large family suggest that the breast-ovarian cancer locus lies between D17S588 and D17S579. PMID- 8460640 TI - Chromosome 17q linkage studies of 18 Utah breast cancer kindreds. AB - In this paper we present linkage results from the analysis of 18 Utah breast cancer kindreds, for three 17q markers. Four kindreds had LOD scores greater than 1.0 for at least one of the marker loci. One of these kindreds has a LOD score of 6.07 with D17S579, and we believe it to be the most informative 17q family reported to date. Among the kindreds which appear unlinked to 17q were an early onset breast cancer family, a large breast-ovarian family, and a kindred with mixed age at onset. Analysis of individual recombinants in the linked families localizes the BRCA1 gene between THRA1 and D17S579 (Mfd188). A comparison of the Cancer and Steroid Hormone Study (CASH) model and a model which assumes a rare dominant susceptibility locus with low penetrance and no phenocopies stresses the difficulties in assessing linkage if the assumptions of the CASH model in terms of age at onset of breast cancer are not appropriate for the BRCA1 locus. A hypothetical breast cancer pedigree is used to calculate gene carrier probabilities under the CASH model, thereby illustrating some of our concerns regarding the use of this model to detect and exclude 17q linkage in breast cancer families. PMID- 8460641 TI - Linkage analysis with markers on 17q in 29 Swedish breast cancer families. AB - Recently, a putative breast cancer gene was localized to the long arm of chromosome 17. A collaboration study was undertaken to confirm linkage, to further map the gene, and to determine to what extent breast cancer families are linked to this locus. The Swedish material consisted of 29 breast cancer families in which 68 affected members were studied. Linkage analysis of breast cancer susceptibility was performed with a number of markers on 17q. In this material a weakly positive LOD score in favor of linkage was observed in a subgroup of families with early onset, while no such linkage was observed in a subgroup of families with late onset. PMID- 8460642 TI - Genetic heterogeneity and localization of a familial breast-ovarian cancer gene on chromosome 17q12-q21. AB - In a study of 31 breast cancer families and 12 breast-ovarian cancer families, we have obtained clear evidence of linkage to markers on chromosome 17q in the families with ovarian cancer (maximum lod score 3.34 at theta = .04) but only weak evidence in those without ovarian cancer. Recombinant events indicate that the gene lies between D17S588 and D17S250. PMID- 8460643 TI - Linkage analysis of early-onset breast and ovarian cancer families, with markers on the long arm of chromosome 17. AB - We have conducted linkage analysis in 16 breast cancer families, 13 of which are classified as site-specific breast cancer families and 3 of which are classified as breast-ovary families. Linkage analysis has largely focused on a single extended breast-ovary family. Analysis of all families combined shows significant evidence for linkage to 17q (LOD = 3.63 at theta = .0, for linkage to NME1), confirming the observations of Hall et al. and Narod et al. Many families were consistent with linkage, but their limited size and informativeness precluded confirmation of linkage. A putative recombinant in a breast-ovary family suggests that BRCA1 is distal to D17S250. PMID- 8460644 TI - A linkage study in seven breast cancer families. AB - Seven breast cancer families are examined for evidence of linkage to a site in the region of 17q12-q21, by using five markers. The families constitute a subset of a larger series of familial breast cancer; the seven families were selected because constitutional DNA was available on informative members, either from clinical samples or extracted from paraffin blocks. Two-point lod scores are reported. The maximum lod score, 0.8824, is obtained with marker NM23 at theta = 0. This is clearly not significant in itself; however, when taken in context with evidence from existing reports, it provides support for linkage to this region. PMID- 8460645 TI - Linkage analysis in German breast cancer families with early onset of the disease, using highly polymorphic markers from the chromosome 17q11-q24 region. AB - Linkage analysis in German breast cancer families with early onset of the disease by using six markers on chromosome 17q11-q24 has been carried out. In the region between markers D17S250 and GH, three markers showed positive LOD scores at an estimated distance of zero. Evidence for linkage is greatest for D17S250, with a LOD score of 2.42. PMID- 8460646 TI - BRCA1 maps proximal to D17S579 on chromosome 17q21 by genetic analysis. AB - Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. These markers define the location of a gene (BRCA1) which appears to be inherited as an autosomal dominant susceptibility allele. We analyzed five families with multiple affected individuals for evidence of linkage to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, suggesting that the gene is proximal to the marker D17S579 (Mfd188). These findings are consistent with the maximum-likelihood position estimated by the Breast Cancer Linkage Consortium and with recombination events detected in other linked families. Linkage analysis was greatly aided by PCR based analysis of paraffin-embedded normal breast tissue from deceased family members, demonstrating the feasibility and importance of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail. PMID- 8460647 TI - Detection of aneuploid human sperm by fluorescence in situ hybridization: evidence for a donor difference in frequency of sperm disomic for chromosomes 1 and Y. AB - Fluorescence in situ hybridization with repetitive-sequence DNA probes was used to detect human sperm disomic for chromosomes 1 and Y in three healthy men. Data on these same men had been obtained previously, using the human-sperm/hamster-egg cytogenetic technique, providing a cytogenetic reference for validating sperm hybridization measurements. Air-dried smears were prepared from semen samples and treated with DTT and lithium diiodosalicylate to expand sperm chromatin. Hybridization with fluorescently tagged DNA probes for chromosomes 1 (pUC177) or Y (pY3.4) yielded average frequencies of sperm with two fluorescent domains of 14.2 +/- 2.4/10,000 and 5.6 +/- 1.6/10,000 sperm, respectively. These frequencies did not differ statistically from frequencies of hyperploidy observed for these chromosomes with the hamster technique. In addition, frequencies of disomic sperm from one donor were elevated approximately 2.5-fold above those of other donors, for both chromosomes 1 (P = .045) and Y (P = .01), consistent with a trend found with the hamster technique. We conclude that fluorescence in situ hybridization to sperm chromosomes provides a valid and promising measure of the frequency of disomic human sperm. PMID- 8460648 TI - Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology. AB - Our aim was to determine the population frequencies of the major slow acetylator alleles of the polymorphic N-acetyltransferase (NAT2) gene, whose locus maps to chromosome 8. We used allele-specific PCR amplification on 786 dried blood spots obtained from Hong Kong Chinese, U.S. Koreans, U.S. blacks, U.S. Hispanics, Germans, and U.S. whites. Our results show that four slow acetylator alleles can be detected as mutations at positions 481, 590, and 857 in the NAT2 gene. Recognized base substitutions at positions 341 and 803 need not be determined, because they were almost always associated with the 481T mutation. The known mutation at position 282 was strongly associated with the 590A mutation. The 481T, 590A, and 857A mutations accounted for virtually all of the slow acetylator alleles in Asian and white populations. The 857A mutation proved to be an Asiatic allele. The results will be useful in large-scale epidemiologic studies of cancer and other conditions potentially associated with the acetylator polymorphism. PMID- 8460649 TI - Pseudoautosomal marker DXYS20 and manic depression. PMID- 8460650 TI - Incorrect genetic counseling of a couple with beta-thalassemia, due to incomplete testing. PMID- 8460651 TI - Age differences in stable carbon and nitrogen isotope ratios in a population of prehistoric maize horticulturists. AB - Stable carbon isotope ratios in prehistoric human bone collagen have been used extensively to document the introduction and intensification of maize horticulture in notheastern North America. Most previous studies are based on small samples of adults who are assumed to characterize the diet of the population. In this study, all 29 individuals buried within an Ontario Iroquoian village site dated A.D. 1530-1580 were analysed for stable isotopes of carbon and nitrogen. Age distribution of the sample ranges from preterm to elderly. Significant negative correlations between age and delta 13C, and age and delta 15N values were found. High delta 13C values in infants and young children (delta 13C = -6.8 to -12.3) suggest a weaning diet high in maize. High delta 15N values in infants relative to adults suggest a trophic level effect during breast feeding which has been reported in a modern sample by Tuross et al. (Am. J. Phys. Anthropol., 1993). In addition to the isotopic evidence for extremely high carbohydrate (maize) intake, the MacPherson sample includes two juveniles aged 3 4 years, exhibiting circular caries. No other cases of this condition are known in the extensively studied southern Ontario skeletal collections. Together the evidence from dentition and stable carbon isotopes indicates a very high carbohydrate diet in subadults. Circular caries result from developmental stress during enamel formation with subsequent caries formation in areas of thinner enamel. These findings are relevant to studies of infant and early childhood morbidity and mortality among prehistoric maize horticulturists. PMID- 8460652 TI - Occipital lesions: a possible cost of cradleboards. AB - This examination of a Mimbres-Mogollon pueblo skeletal sample reveals a surprising percentage of individuals with occipital lesions. Each lesion is located in the approximate center of the squama immediately superior to the external occipital protuberance. Notably, no child over the age of 1 year exhibits a lesion that would have been active at the time of death, but a number of older children and adults exhibit evidence of healed lesions in this same area on the occipital. The restricted nature of these lesions, in terms of both their locations and ages of those actively affected, suggests that the use of cradleboards may have been at least a contributing, if not initiatory, factor in their creation. Specifically, this study suggests that the pressure and friction of an infant's head against a cradleboard may have 1) produced ischemic ulcers, 2) produced the conditions favorable for bacterial infections such as impetigo or carbuncles, or 3) complicated the treatment of other infections appearing on the back of the scalp. PMID- 8460653 TI - Elastic properties of human supraorbital and mandibular bone. AB - Elastic constants, including the elastic modulus, the shear modulus, and Poisson's ratio, were measured on human craniofacial bone specimens obtained from the supraorbital region and the buccal surfaces of the mandibles of unembalmed cadavers. Constants were determined using an ultrasonic wave technique in three directions relative to the surface of each sample: 1) normal, 2) tangential, and 3) longitudinal. Statistical analysis of these elastic constants indicated that significant differences in the relative proportions of elastic properties existed between the regions. Bone from the mandible along its longitudinal axis was stiffer than bone from the supraorbital region. Directional differences in both locations demonstrated that cranial bone was not elastically isotropic. It is suggested that differences in elastic properties correspond to regional differences in function. PMID- 8460654 TI - Increasing human tooth length between birth and 5.4 years. AB - Most previous studies of tooth development have used fractional stages of tooth formation to construct growth standards suitable for aging juvenile skeletal material. A simple alternative for determining dental age is to measure tooth length throughout development. In this study, data on tooth length development are presented from 63 individuals of known age at death, between birth and 5.4 years, from an archeological population recovered from the crypt of Christ Church, Spitalfields, London. Isolated developing teeth (304 deciduous, 269 permanent) were measured in millimeters and plotted against individual age. Regression equations to estimate age from a given tooth length, are presented for each deciduous maxillary and mandibular tooth type and for permanent maxillary and mandibular incisors, canines, and first permanent molars. Data on the earliest age of root completion of deciduous teeth and initial mineralization and crown completion of some permanent teeth in this sample are given, as well as the average crown height and total tooth length from a small number of unworn teeth. This method provides an easy, quantitative and objective measure of dental formation appropriate for use by archeologists and anthropologists. PMID- 8460655 TI - Sexual dimorphism in large-bodied primates: the case of the subfossil lemurs. AB - Large body size has evolved repeatedly in the order Primates, not merely among anthropoids but also among prosimians. Whereas high degrees of sexual size dimorphism characterize many of the large-bodied anthropoids, this is not the case for extinct large-bodied lemurs. This paper uses finite mixture analysis and other techniques to ascertain just how much skull length dimorphism might be embedded in the generally unimodal distributions of skull lengths of giant extinct lemurs from single localities, and then compares these results with known skull length dimorphisms in extant lemurs and large-bodied catarrhines. We show that low levels of skull length sexual dimorphism (or none at all) characterize subfossil lemurs, and we explore several possible explanations for this phenomenon. Traditional explanations of sexual size dimorphism generally focus on body size or mating systems. These are not sufficient to explain the variation in sexual dimorphism that can be observed in the order Primates. PMID- 8460656 TI - Inbreeding avoidance in rhesus macaques: whose choice? AB - Whether nonhuman primates avoid copulating with close kin living in their social group is controversial. If sexual aversion to relatives occurs, it should be stronger in females than in males because of females' greater investment in each offspring and hence greater costs resulting from less viable offspring. Data presented here show that adult male rhesus macaques breeding in their natal groups at Cayo Santiago experienced high copulatory success, but copulated less with females of their own matrilineages than with females of other matrilineages. Adult females were never observed to copulate with males of their own matrilineage during their fertile periods. Although natal males sometimes courted their relatives, examination of two measures of female mate choice showed that females chose unrelated natal males over male kin. Female aversion to male kin was specific to the sexual context; during the birth season, females did not discriminate against their male relatives in distributing grooming. Evolved inbreeding avoidance mechanisms probably produce different outcomes at Cayo Santiago than in wild rhesus macaque populations. Gender differences in sexual aversion to relatives may be partly responsible for differences between studies in reported frequency of copulations by related pairs. PMID- 8460657 TI - Divergence between biochemical and cytogenetic differences in three species of the Callicebus moloch group. AB - Specimens from three species of the Callicebus moloch group--C. moloch (N = 80), C. brunneus (N = 166), and C. cupreus (N = 23)--were studied. Twenty genetic loci were investigated through electrophoresis, genetic distances were estimated, and the results compared with the available cytogenetic data. Low values of genetic distance were encountered, contrasting with relatively large chromosome differences. We propose that recent karyotypic rearrangements, rather than other Pleistocene events, were the major evolutionary mechanisms determining speciation in these three taxa. PMID- 8460658 TI - Stature reconstruction from long bones in ancient population samples: an approach to the problem of its reliability. AB - Stature estimates provided by the application of the anatomical method of Fully and Pineau (1960) to well preserved Neolithic skeletons (39 males and 27 females) from seven different European countries are compared with those drawn from lower extremity components by means of regression equations commonly used to predict stature of earlier European populations. The analysis of data, carried out with reference both to the sample of origin of the skeletons and to stature classes, suggests that the equations of Pearson (1899) and of Trotter and Gleser for Negroes (1952, 1977) yield very good estimates in female samples, leading to errors below 2 cm in most of the cases. These equations, and those of Olivier et al. (1978), prove useful for stature reconstruction in males too, with the exception of very low (below 154 cm) and very tall (over 179 cm) individuals. Formulae of Breitinger (1938) yield values consistent with those resulting from the anatomical method only within a range including medium-high statures, while the corresponding Bach (1965) formulae for females provide poor approximations. The Trotter and Gleser formulae for Whites (1952) yield very unsatisfactory evaluations, except in specimens taller than 180 cm, and usually overestimate stature both in male and in female skeletons. The results obtained from the long bones by means of alternative approaches to the least-squares regression formulae (Model II regression, and femur/stature ratio) and their efficacy in predicting stature of the samples under study is discussed in the final part of the paper. PMID- 8460659 TI - Periodontal health in free-ranging baboons of Ethiopia and Kenya. AB - Frontal and lateral intraoral photographs of 19 baboons from the Awash National Park, Ethiopia and 37 baboons from Amboseli National Park, Kenya, were used to assess periodontal health. The Awash baboons, and two groups (Alto's and Hook's) at Amboseli, fed entirely from natural sources, but baboons from the third Amboseli group (Lodge) fed largely on food refuse from one of the park's lodges. Juveniles and adults were evaluated separately. Intraoral photographs were seriated based on visual appraisals of periodontal health. In both age groups, the best periodontal health was seen in Awash animals; Alto's and Hook's animals were intermediate, and the poorest health was seen in the Lodge sample. The periodontal health decreased with age in adult baboons, as reported in humans. Geochemistry, genetics, age, and diet (particularly variations in bacterial flora) were considered as factors contributing to the intergroup differences. Although it is not possible at present to exclude any of these as a contributing cause, we consider that diet in the broad sense (including food, water, and contamination by oral bacteria of human origin) probably plays a major role. PMID- 8460660 TI - Technical note: an electronic caliper designed for measuring bone breadths in living subjects. PMID- 8460661 TI - Human cranial variability: a methodological comment. PMID- 8460662 TI - Role of polyamines in the regulation of proliferation and hormone production by insulin-secreting cells. AB - This paper focuses on the mechanisms regulating proliferation and insulin production by normal and tumoral pancreatic beta-cells. In particular, the evidence for involvement of polyamines is reviewed. Pancreatic islet cells contain high levels of polyamines, and based on findings obtained using enzyme directed inhibitors, it appears that putrescine and spermidine are necessary for proinsulin biosynthesis, whereas spermine may exert a stimulatory or permissive role in RNA transcription-stabilization and long-term insulin release. Islet polyamine content is not altered by short-term secretory stimulation, nor is the acute secretory response impeded by polyamine synthesis inhibitors, making it unlikely that these amines play any major role in short-term insulin release. Various mitogens increase islet polyamine contents and DNA synthesis, but increases in cytosolic polyamines do not seem to mediate their mitogenicity. Nuclear polyamine content is not altered by the inhibitors, suggesting that maintenance of polyamines within this organelle may be sufficient to sustain elevated DNA synthesis. In tumoral RINm5F cells, polyamine depletion results in decreased proliferation and increased cellular content of insulin and insulin secretory granules without affecting insulin mRNA levels or translation. Moreover, polyamine-depleted RINm5F cells display improved substrate metabolism and sensitivity of the stimulus-secretion coupling. Possible levels of polyamine interaction with Ca2+ metabolism are discussed. PMID- 8460663 TI - Staurosporine induced Ca2+ increase in DDT1MF-2 smooth muscle cells. AB - The free calcium concentrations in nucleus ([Ca2+]n) and cytoplasm ([Ca2+]c) of cultured DDT1MF-2 smooth muscle cells were estimated using the fluorescent dye indo-1 and laser confocal microscopy. The alkaloid staurosporine mainly increased [Ca2+]c during the initial minutes of stimulation and the nucleocytoplasmic gradient was maintained. Thereafter [Ca2+]n increased further while [Ca2+]c decreased, resulting after 10 min in a reversion of the nucleocytoplasmic gradient. Staurosporine increased the Ca2+ influx but also released intracellular Ca2+. In Ca(2+)-free solution no inversion of the nucleocytoplasmic gradient was seen in most cells. Ca2+ increased more rapidly in the area of the perinuclear sarcoplasmic reticulum (SR) than in the central cytoplasm. This is suggestive of the release of Ca2+ from this region. Ca2+ concentration remained also enhanced near the plasmalemma during this time period. This might indicate that the efflux mechanism is also affected. It is unlikely that these changes are due to inhibition of protein kinase C, since phorbol esters are ineffective and since downregulation by prolonged incubation with phorbol 12-myristate 13-acetate only affected the time periods required to attain the described [Ca2+]c and [Ca2+]n peaks. The slow time course of the staurosporine effects allowed demonstration of the spatiotemporal Ca2+ gradients between the nucleus and the cytoplasm and also inside the cytosol. The different time course of the increases in [Ca2+]c and [Ca2+]n suggests that two different Ca2+ mobilization events are present. The occurrence of an inversion of the nucleocytoplasmic gradient whereby [Ca2+]n increased while [Ca2+]c values decreased indicates that the increase in [Ca2+]n might result partially from release sites inside the nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460664 TI - Low-affinity mixed acetylcholine-responsive receptors at the apical membrane of frog tadpole skin. AB - The larval frog skin has a very high electrical resistance and a corresponding low rate of transepithelial ion transport. Amiloride, a blocker of sodium transport in adult skin, transiently stimulates rather than inhibits short circuit current (Isc) across larval skin through nonselective cation channels. Acetylcholine (ACh) stimulates Isc like amiloride, although the response is more prolonged. Pretreatment with ACh markedly suppressed amiloride stimulation of Isc; amiloride pretreatment also suppressed ACh stimulation. Half-maximal stimulation of Isc by ACh occurred at 347 microM. Stimulation by ACh was inhibited by both d-tubocurarine [dissociation constant (Kd) = 57 microM] and atropine (Kd = 49 microM). The specific nicotinic agonist 1,1-dimethyl-4 phenylpiperazinium and the specific muscarinic agonist oxotremorine-M both stimulated Isc and were blocked by either atropine or d-tubocurarine. Reciprocal desensitization and blocker cross-reactivity suggest that ACh activates the same population of receptors as amiloride. This ACh-responsive receptor has characteristics of both nicotinic and muscarinic receptors found in other tissues. PMID- 8460665 TI - Intracellular tetanic calcium signals are reduced in fatigue of whole skeletal muscle. AB - Force and intracellular calcium signals were monitored in whole bullfrog semitendinosus muscles during fatigue produced by intermittent tetanic stimulation. Intracellular calcium signals were monitored using the fluorescent calcium-sensitive indicator indo-1 from the ratio of fluorescence intensities (R) at 400 and 470 nm. Fatiguing stimulation caused 1) proportional decreases of tetanic force and R, suggesting a component of the decreased force during fatigue of whole muscle may be due to insufficient calcium to activate contraction; 2) a progressive slowing of the relaxation of both force and R, suggesting slowed force relaxation may be mediated by slowed calcium removal from the myoplasm; 3) an increase of resting level R, suggesting impaired calcium removal from, or increased leakage to the cytosol; 4) prolongation of the twitch contraction, which was paralleled by changes in R. These findings are consistent with previous single fiber studies and suggest that changes in whole muscle contractility with fatigue may be partially mediated by changes in calcium handling by the cell. PMID- 8460666 TI - Effects of arginine vasopressin and atriopeptin on glial cell volume measured as 3-MG space. AB - This study evaluates the hypothesis that arginine vasopressin (AVP) and atriopeptin, peptide hormones synthesized and released within the brain, are regulators of brain cell volume using cultured astroglial cells derived from newborn rats. Cell water content, regarded as volume, was measured in defined, serum-free medium as the 3-O-methylglucose (3-MG) space. Initial experiments established conditions such that glucose, which competes with 3-MG for the glucose carrier, would not interfere with the measurement of the 3-MG space. AVP increased the 3-MG space of glial cells by an average of 25% between 30 and 120 min of exposure, whereas atriopeptin decreased it by 32%. The 3-MG space remained close to normal after coadministration of both peptides. The AVP-dependent increase in 3-MG space was blocked both by the V1 antagonist d(CH2)5Tyr(Me)AVP (Manning compound) and by the cotransport inhibitor, bumetanide. Results are consistent with a role for AVP and atriopeptin in the homeostasis of atroglial cell volume. PMID- 8460667 TI - Stimulation of phospholipase D activity and phosphatidic acid production by norepinephrine in rat aorta. AB - We sought to relate norepinephrine (NE) stimulation of phosphatidic acid (PA) production to functional responses of rat aorta and pathways for PA production. The time course for changes in PA was closely related to Ca-dependent tonic responses in 42K efflux and contraction. NE (30 microM for 1 min) increased PA and reduced phosphatidylcholine (PC) and phosphatidylinositol (PI) based on Pi analyses and 32P labeling of phospholipids. The 32P-to-Pi ratio in PA (0.8 +/- 0.2, n = 13) was similar to PC (0.8 +/- 0.1, n = 14) but was significantly lower (P < 0.001) than PI (4.6 +/- 0.5, n = 14). The 32P-to-Pi ratio in PA was also lower (P < 0.02) than phosphatidylinositol phosphate and phosphatidylinositol bisphosphate. NE also increased [3H]PA twofold (P < 0.05) when PC was selectively labeled with [3H]myristic acid. These observations are more consistent with PA being formed from the hydrolysis of PC by phospholipase D (PLD) than by the phosphorylation of diacylglycerol produced by the action of phospholipase C. PLD was assayed by the formation of phosphatidylethanol (PEt) via a transphosphatidylation reaction with ethanol (half-maximal stimulation at 0.4 0.5% vol/vol). The time course for PLD stimulation by NE was similar to PA, with significant increases (P < 0.002) during 10 s to 30 min exposure. Once formed, PEt was degraded slowly, with a half time > 3 h. It is concluded that NE stimulates PLD in rat aorta, which forms a significant amount of PA from the hydrolysis of PC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460668 TI - Inhibition of slow-wave repolarization and Ca(2+)-activated K+ channels by quaternary ammonium ions. AB - We studied the effects of the K+ channel blocker tetrapentylammonium (TPeA) on the electrical activity of intact circular smooth muscle from canine colon. TPeA (10 and 20 microM) increased slow-wave duration and "locked" the membrane potential around -30 mV plateau potential after several minutes of application, suggesting that K+ channels are essential for termination of colonic slow waves. Repolarization and normal slow-wave activity resumed after 20-30 min of washout. The patch-clamp technique was used to study the block of large-conductance Ca(2+) activated K+ channels (BK channels) by TPeA and tetraethylammonium (TEA) in excised and cell-attached patches from isolated colonic smooth muscle cells. Channel block was characterized by a voltage-dependent dissociation constant [Kd(V)] for the binding of TEA and TPeA to a blocking site located a fraction of the distance across the membrane field (delta). The extracellular TEA binding site had a Kd(0) of 0.33 mM and a delta of 0.23. The extracellular TPeA binding site had a Kd(0) of 2.2 mM but showed significantly less voltage dependence (delta = 0.02). The intracellular binding site for TEA was of low affinity [Kd(0) = 76 mM]. Intracellular TPeA was the most potent blocker of BK channel current [Kd(0) = 11.7 microM]. The voltage dependence of block by intracellular TPeA (delta = -0.21) was not significantly different from that of intracellular TEA (delta = -0.3). Internal TPeA (10 microM) also blocked a 70-pS K+ channel and a 23-pS K+ channel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460669 TI - Refilling the inositol 1,4,5-trisphosphate-sensitive Ca2+ store in neuroblastoma x glioma hybrid NG108-15 cells. AB - Bradykinin-induced increases in the intracellular free Ca2+ concentration ([Ca2+]i) were recorded in single NG108-15 cells with indo-1-based dual-emission microfluorimetry (50% effective concentration, 16 nM). A 1-min exposure to 30 nM bradykinin completely depleted the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store; refilling the store required extracellular Ca2+ (half time, 2 min). Refilling the IP3-sensitive store was completely blocked by 1 microM La3+ and 10 microM nitrendipine, but not 10 microM verapamil, 10 microM flunarizine, 1 microM nitrendipine, or 0.1 microM La3+. Thapsigargin irreversibly depleted the Ca2+ store and prevented its refilling (half-maximal inhibitory concentration, 3 nM). Influx of Ca2+ across the plasma membrane did not increase after depletion of the IP3-sensitive store by exposure to bradykinin, although maintained presence of the agonist produced significant Ca2+ influx. Similarly, Mn2+ and Ba2+ influx, as measured by indo-1 quenching and spectral shifts, did not increase following depletion of IP3-sensitive store. In contrast to depletion of the IP3-sensitive Ca2+ store by bradykinin, thapsigargin (10 nM) treatment produced Ca2+ and Ba2+ influx. We conclude that after Ca2+ mobilization, the IP3-sensitive Ca2+ store in NG108-15 cells is refilled with cytoplasmic Ca2+ via a thapsigargin-sensitive Ca(2+)-Mg(2+)-ATPase. Cytoplasmic Ca2+ is replenished by a persistent leak of Ca2+ across the plasma membrane. This leak is not modulated by the status of the intracellular Ca2+ store. In NG108-15 cells, agonist and thapsigargin-evoked Ca2+ entry are mediated by activation of plasmalemmal Ca2+ channels independent of the status of the IP3-sensitive intracellular Ca2+ store. PMID- 8460670 TI - Regulation of the mitochondrial ATP-Mg/Pi carrier in isolated hepatocytes. AB - This study investigated the cellular regulation of net adenine nucleotide movements between the cytoplasm and mitochondria in intact cells. Such movements are presumed to occur primarily by ATP-Mg exchange with Pi via the mitochondrial ATP-Mg/Pi carrier. Vasopressin, A23187, and thapsigargin all elevate intracellular free [Ca2+] and all caused dose-dependent increases in the mitochondrial adenine nucleotide content (29, 63, and 39%, respectively). Phorbol 12-myristate 13-acetate had no effect. The effect of vasopressin was abolished when cytoplasmic [ATP] was decreased (by 43%) and [Pi] was increased (3-fold) by addition of carboxyatractyloside. The effect of thapsigargin was abolished by addition of xylulose to deplete cytoplasmic [ATP] (by 50%) and [Pi] (> 4-fold). The results indicate that in intact cells Ca2+ activates the mitochondrial ATP Mg/Pi carrier to enable changes in the subcellular distribution of adenine nucleotides and that the relative [ATP] and [Pi] gradients govern the direction and magnitude of net adenine nucleotide movements between the cytoplasm and mitochondria. PMID- 8460671 TI - Elevation of inositol tetrakisphosphate parallels inhibition of Ca(2+)-dependent Cl- secretion in T84 cells. AB - Carbachol and histamine both stimulate calcium-dependent chloride secretion in the colonic epithelial cell line, T84. However, pretreatment of cell monolayers with carbachol blocks subsequent chloride secretion induced by thapsigargin but not the calcium elevation stimulated by this agent, whereas histamine pretreatment blocks neither thapsigargin-induced chloride secretion nor calcium elevation. To examine whether inositol phosphate metabolism might account for this difference, we measured levels of radiolabeled inositol phosphates: Ins(1,3,4)P3, Ins(1,4,5)P3, Ins(1,3,4,5)P4, Ins-(1,3,4,6)P4, Ins(3,4,5,6)P4, InsP5, and InsP6 after cell stimulation. Although both carbachol and histamine increase Ins (1,4,5)P3 at 5 s, there is a greater and more persistent increase in the levels of Ins(1,3,4)P3 and InsP4 at later time points after carbachol than histamine, which corresponded to the suppression of the chloride secretory response. PMID- 8460672 TI - Acid and base effects on avian osteoclast activity. AB - Osteoclasts generate a massive acid flux to mobilize bone calcium. Local extracellular acidification by polarized vacuolar-type H(+)-ATPase, balanced by contralateral HCO3-(-)Cl- exchange to maintain physiological intracellular pH, is theorized to drive this process. It follows that extracellular pH, PCO2, or HCO3- concentration ([HCO3-]) should impact bone matrix dissolution. However, the effects on bone resorption of the concentrations of these ions or their transmembrane gradients are unknown. Furthermore, because bone management is a vital process, regulatory feedback may minimize such effects. Thus a complex relationship between bone resorption and pH, PCO2, and [HCO3-] is expected but requires experimental determination. We measured bone resorption by isolated avian osteoclasts while varying these parameters across the physiological range. Bone degradation increased 50% from pH 7.3 to 6.7, whether achieved by changing [HCO3-] (2.3-38 mM) at constant HCO3- or PCO2 (15-190 mmHg) at constant [HCO3-]. However, at constant pH, changing PCO2 and [HCO3-] within physiological limits did not affect bone resorption. In contrast, total HCO3- removal at pH 7.4 reduced bone degradation by rat or avian osteoclasts substantially, confirming that normal acid secretion requires HCO3-. These observations support a model coupling osteoclastic bone resorption to proton and HCO3- transport but indicate that [HCO3-] is not rate limiting under physiological conditions. Extracellular pH changes affect osteoclastic bone resorption measurably, but not dramatically, at physiological [HCO3-]. PMID- 8460673 TI - ATP synthase activity is required for fructose to protect cultured hepatocytes from the toxicity of cyanide. AB - The contributions of the loss of the mitochondrial membrane potential (MMP) and a depletion of ATP to the genesis of lethal injury were evaluated in the killing of cultured hepatocytes by cyanide (CN). The glycolytic production of ATP from fructose (Fru) maintained the MMP and prevented the killing by CN. Inhibition of the mitochondrial ATP synthase by 0.1 micrograms/ml oligomycin (Oligo) reduced ATP stores at the same rate and to the same extent as did 1 mM CN. With Oligo there was no loss of the MMP, and the hepatocytes maintained viability over the 6 h during which CN killed all of the cells. Oligo had no effect on the rate of killing by CN. However, Oligo reversed the protective effect of Fru on CN-induced killing, a result that correlated with the loss of MMP but not with the depletion of ATP. Neither Fru nor Oligo affected the intracellular acidosis achieved with CN alone. Fru also prevented toxicity of the uncoupler carbonyl cyanide m chlorophenylhydrazone (CCCP), a result that correlated with the preservation of MMP. Oligo potentiated the toxicity of CCCP. It is concluded that a functioning mitochondrial ATP synthase is required for the production of ATP from Fru to prevent the killing of hepatocytes by CN. The extent of killing correlated closely with changes in the MMP but not with changes in the content of ATP. PMID- 8460674 TI - Molecular adaptation of vascular endothelial cells to oxidative stress. AB - Cellular organisms respond at the cellular and molecular level when confronted with sudden changes in environment, and molecular adaptation represents the ability of the cells to acclimate themselves to their new environment. In this study we examined the response of bovine vascular endothelial cells (VEC) to the oxidative stress by exposing the cultured cells to two different concentrations of H2O2, 0.04 or 0.08 mM, for 18-24 h. H2O2-exposed VEC displayed good viability (85-90% for 0.04 mM H2O2; 75-80% for 0.08 mM H2O2) and exhibited normal morphology. H2O2 treatment of the VEC was associated with the expression of a number of new proteins, as demonstrated by two-dimensional gel electrophoresis of total cell lysate. Cells exposed to 0.04 mM H2O2 expressed 25 new proteins, whereas 19 newly expressed proteins were detected when the cells were exposed to 0.08 mM H2O2. Western blot analysis of H2O2-treated VEC using specific antibodies to heat-shock proteins (HSP) identified one of these proteins as a member of the HSP 70 family. In addition, H2O2 induced an increase in antioxidative enzyme activities in the VEC, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, these changes were a truly adaptive phenomenon because challenging the VEC with brief exposure to toxic levels of H2O2 (1 mM for 30 min) showed increased viability (by Trypan blue exclusion test) and decreased injury (by lactate dehydrogenase supernatant-to-cellular ratio determination) in adapted cells (preexposed to 0.04 or 0.08 mM H2O2) compared with control cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460675 TI - Modulation of cytokines and myocardial lesions by vitamin E and chloroquine in a Mg-deficient rat model. AB - Antioxidant treatment with alpha-tocopherol did not affect the level of the "inflammatory cytokines" in Mg-deficient animals, although it diminished the extent of the myocardial lesions. In another group of Mg-deficient animals chloroquine treatment diminished significantly the levels of circulating cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and also resulted in a major decrease in myocardial lesions. These results raise the question of the role of these inflammatory cytokines in the formation of lesions in Mg-deficient myocardium. Because these cytokines are able to stimulate free radical production in various cell types, we postulate that Mg deficiency involves free radical mechanisms that can be amplified by inflammatory cytokines; whether these cytokines initiate lesion formation is unclear. Although our data do not confirm either possibility, we submit that these results implicate a role for the inflammatory cytokines in the cardiac pathology of Mg deficiency. PMID- 8460676 TI - Effects of exercise training on skeletal muscle glucose uptake and transport. AB - Exercise training increases the concentration of GLUT-4 protein in skeletal muscle that is associated with an increase in maximal insulin-stimulated glucose transport. The purpose of this study was to determine whether exercise training results in a long-lasting increase in insulin-stimulated glucose transport in rat skeletal muscle. Glucose uptake and skeletal muscle 3-O-methyl-D-glucose (3-MG) transport were determined during hindlimb perfusion in the presence of a maximally stimulating concentration of insulin (10 mU/ml). Hindlimb glucose uptake was approximately 29% above sedentary (Sed) levels in rats examined within 24 h (24H) of their last exercise session. However, when rats were examined 48 h (48H) after their last exercise session, hindlimb glucose uptake was not different from Sed levels. Maximal 3-MG transport was enhanced, above Sed levels, in red (RG; 72% increase) and white (WG; 44% increase) gastrocnemius and plantaris (Plan; 67% increase) muscles, but not soleus (Sol), of 24H rats. GLUT-4 protein content was significantly elevated in those muscles that exhibited enhanced 3-MG transport in 24H rats. GLUT-4 protein content was also elevated in RG, WG, and Plan of 48H rats and was not different from 24H rats. Despite the elevated GLUT-4 protein content, 3-MG transport in 48H rats was only slightly, although statistically not significantly, higher than in Sed rats. These results provide evidence that exercise training does not result in a persistent increase in skeletal muscle glucose uptake or transport, despite an increase in GLUT-4 protein content. PMID- 8460677 TI - Deoxygenation-induced cation fluxes in sickle cells. III. Cation selectivity and response to pH and membrane potential. AB - Deoxygenation of sickle cells increases membrane permeability to Na, K, and Ca and contributes to cellular cation depletion. This study examines the physiological nature of the pathway that mediates deoxygenation-induced movements of monovalent cations. Deoxygenation-induced Rb influx was a linear function of external Rb concentration, with no evidence of saturation. Activation of the deoxygenation-induced pathway was fostered by alkaline pH (7.5), whereas ion movements via the activated pathway were optimal between pH 6.9 and 7.0 in cells incubated in media in which NO3 replaced Cl to eliminate KCl cotransport. The deoxygenation-induced pathway exhibited no selectivity among the alkali metal cations Li, Na, K, Rb, or Cs, but the monovalent organic cations tetramethylammonium, tetraethylammonium, and N-methylglucamine were excluded. Sickle cells incubated in low-Cl media (external Cl, 40 mM) to depolarize the membrane exhibited increased deoxygenation-induced K efflux and reduced Na influx. Cells treated with valinomycin to hyperpolarize the membrane showed increased deoxygenation-induced Na influx. These characteristics of the deoxygenation-induced transport pathway, linear concentration dependence, lack of cation selectivity, and response to membrane potential, argue against a carrier mediated mechanism in favor of a diffusional process. The exclusion of small organic cations, however, suggests that factors other than ion size influence deoxygenation-induced permeability. PMID- 8460678 TI - Intracellular pH determination by 13C-NMR spectroscopy. AB - A noninvasive method for the determination of pH by the 13C-nuclear magnetic resonance (NMR) chemical shift of the C-3 carbon of sn-glycerol 3-phosphate is described. Nonlinear least-squares analysis of the chemical shift variation of the C-3 resonance of sn-glycerol 3-phosphate with pH at 37 degrees C in solutions and in perchloric acid extracts of tissue yielded a pKa of 6.2, making it a very sensitive indicator of pH in the approximate range of 5-7. Intracellular pH determined by the present 13C-NMR method correlated well with simultaneous measurements of pH by 31P-NMR spectroscopy over a wide range during normal perfusion and ischemic conditions in intact rat hearts. These findings indicate that this approach is particularly suited for quantification of intracellular pH over the physiological range in intact tissues and that observed in ischemic myocardium. PMID- 8460679 TI - Glucose transporters and glucose transport in skeletal muscles of 1- to 25-mo-old rats. AB - It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT 4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460680 TI - Glucose uptake and glycogen synthesis in normal and chronically active muscles. AB - The hindlimb muscles of the C57Bl6J dy2J/dy2J (dy2J) mouse suffer from a chronic neural stimulation (pseudomyotonia), resulting in increased contractile activity. In response to the increased contractile activity, these muscles store increased amounts of glycogen. In this study, glucose uptake and glycogenesis (glycogen synthesis from glucose) were analyzed in chronically active and normal muscles. In vivo experiments demonstrate increased 3-O-methylglucose (3-MG) uptake rates and glycogenesis by chronically active dy2J gastrocnemius muscles (Gast) vs. normal control Gast. The chronically active diaphragm muscle (Dia) showed the highest rates of 3-MG uptake, as well as glycogenesis in vivo when compared with other skeletal muscles. No differences were observed between dy2J and control Dia. The levels of blood glucose were similar between dy2J and control animals. In vitro experiments demonstrated an increased sensitivity and responsiveness to insulin for glucose uptake in the dy2J soleus muscle (Sol). Glycogenesis by dy2J Sol was elevated only at the highest insulin concentration tested (10,000 microU/ml). In contrast, the dy2J extensor digitorum longus muscle had an increased sensitivity and responsiveness to insulin for both glucose uptake and glycogenesis. This study demonstrates that chronically active muscles have elevated capacities for glucose uptake and glycogenesis and may help to explain the elevated glycogen levels in the dy2J hindlimb muscles. PMID- 8460681 TI - Effects of subbasal insulin infusion on resting and exercise-induced glucose turnover in depancreatized dogs. AB - beta-Adrenergic blockade suppressed lipolysis and normalized the exercise-induced increments in glucose uptake (GlcU) and metabolic clearance rate (MCR) in alloxan diabetic dogs with residual insulin, but not in insulin-deprived depancreatized dogs even when combined with methylpalmoxirate (MP), which suppresses fatty acid oxidation. The effects of a minimal amount of insulin (as in the alloxan-diabetic dog), were studied in depancreatized, 24-h insulin-deprived dogs during rest and treadmill exercise (6 km/h, 10% slope) using a 1/4 basal insulin infusion (50 microU.kg-1.min-1, insulin, n = 6) alone, or with MP (20 mg.kg-1.day orally, 2.5 days, MP+insulin, n = 6). At rest, insulin decreased circulating fatty acids (31%) and Glc (13%) and increased GlcU and MCR (86 and 72%). Glc production was unaffected. MP plus insulin markedly suppressed hepatic fatty acid oxidation, decreased Glc (44%) and Glc production (50%), and markedly increased MCR (128%). The exercise-induced increments in MCR were markedly improved only by MP plus insulin but were still lower than in the propranolol-treated alloxan-diabetic dogs. Plasma Glc inversely correlated with the exercise-induced increase in MCR (r = -0.86). We conclude that 1) acute infusion of subbasal insulin improved GlcU in depancreatized dogs at rest but not during exercise; 2) inhibition of fatty acid oxidation combined with subbasal insulin improved the exercise-induced increase in MCR; and 3) the difference in GlcU and MCR between the MP plus insulin-treated depancreatized dogs and the beta-blockade-treated alloxan diabetic dogs suggests a difference between acute and chronic effects of insulin. PMID- 8460682 TI - Female sex hormones, perinatal, and peripubertal androgenization on hepatocyte insulin dynamics in rats. AB - The effects of female sex hormones on insulin binding and receptor-mediated insulin degradation were investigated in hepatocytes from ovariectomized rats. The influences of perinatal and peripubertal androgenization on these events were examined. Estradiol treatment increased insulin binding and receptor-mediated insulin degradation by increasing cell surface insulin receptor number. Progesterone also increased both binding and degradation, but the increase in degradation exceeded the increase in binding. Perinatal exposure to testosterone blunted the estradiol-induced increase in insulin binding and decreased degradation, whereas the progesterone-mediated increases were completely suppressed. Peripubertal testosterone decreased binding, with a much greater reduction in insulin degradation. Perinatal androgenization did not influence the peripubertal testosterone effects. Thus peripubertal female sex hormones exert regulatory influences on both hepatic cell surface insulin receptor number and postreceptor events mediating insulin degradation. These events are modulated by perinatal and peripubertal exposure to androgens. Abnormalities in sex hormone levels and/or hepatic androgenization could therefore contribute to altered insulin metabolism and hyperinsulinemia in some hyperandrogenized women with abdominal obesity and increased androgenic activity. PMID- 8460683 TI - Effects of cell density on in vitro glucose metabolism by isolated adipocytes. AB - We studied the effect of variable isolated fat cell concentrations (from 0.17 to 1.25 x 10(6) cells/ml) on rate and pattern of basal and insulin-stimulated glucose metabolism by rat epididymal fat cells. Cell concentration did not affect total glucose utilization, but high cell concentrations increased the absolute and relative conversion of glucose to CO2 and glyceride-fatty acids by two- to threefold and decreased the conversion to lactate, pyruvate, and glyceride glycerol when compared with values observed at low cell concentration. When effects of adenosine deaminase (ADA) and N-6(2-phenylisopropyl)adenosine (PIA) were examined, addition of ADA to incubated cells produced no significant changes in the rate or pattern of adipocyte glucose metabolism; PIA had a slight and uniform effect on the conversion of glucose to its metabolic products and minimal effect on insulin-stimulated glucose metabolism. Medium free fatty acid concentration did not change during the incubation at various cell density, but intracellular free fatty acids were found to be inversely related to fat cell density in the medium. Thus a variable fat cell density influences the pattern of adipocyte glucose metabolism in vitro. This effect may be due to variable rates of lipolysis and resulting changes in intracellular fatty acid concentration rather than to adenosine per se. This work has practical implications in the need to define cell density when carrying out in vitro measurements of adipocyte glucose conversion to products. PMID- 8460684 TI - Characterization and ontogeny of endothelin receptors in human placenta. AB - Because of the potent mitogenic and vasoactive properties of endothelin-1 (ET-1) and the presence of its receptor in third trimester placenta, we postulated that ET-1 might be involved in human placental growth and vascularization during development. As an initial approach to test this hypothesis, placental ET receptors were characterized and quantified in each trimester of pregnancy. Membrane-rich particulates were prepared from first-, second-, and third trimester villous human placenta obtained immediately after pregnancy termination or delivery. ET receptors were characterized by radioligand saturation analysis, ligand competition, and reverse transcription-polymerase chain reaction (RT-PCR) to determine the concentration, affinity, and specificity of ET binding sites, and to document the presence of specific ET-receptor subtype mRNA transcripts in placentas from each trimester. Kinetic determinations of 125I-labeled ET-1 binding yielded a Kd = 61 pM, consistent with the equilibrium determinations of 34 +/- 6 pM (n = 11). The concentration of ET receptors decreased significantly from 682 +/- 94 fmol/mg protein (n = 4) in the first trimester to 266 +/- 89 fmol/mg protein (n = 4) in the third trimester. Competition studies with unlabeled ET-1 indicated a single class of binding sites with a Ki = 49 +/- 5 pM (n = 9), whereas competition with ET-3 demonstrated binding sites with two affinities. The predominant sites had a Ki = 84 +/- 14 pM, similar to that for ET 1. The RT-PCR data confirmed that both ETA and ETB receptors mRNA transcripts are expressed in human placenta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460685 TI - Hepatic glucose production and insulin sensitivity and responsiveness in iron deficient anemic rats. AB - We performed euglycemic hyperinsulinemic glucose clamps at insulin infusion rates of 1.9, 4.0, 9.3, and 19.3 mU.kg-1 x min-1 in rats with varying severities of iron deficiency anemia (IDA; mean hemoglobin concentrations of 59, 79, 107, and 137 g/l) to assess the effect of IDA on insulin sensitivity and responsiveness. Glucose appearance and disappearance (Rd) rates were determined using a primed continuous infusion of [3-3H]glucose. Basal plasma glucose and insulin concentrations were similar between the IDA and control rats. Basal hepatic glucose production was significantly (P = 0.0001) elevated in the two most anemic groups (13.6 +/- 2.4 and 12.6 +/- 3.1 vs. 10.6 +/- 2.2 and 10.2 +/- 2.0 mg.kg-1 x min-1). A significant upward shift in the insulin dose-response curves for Rd indicated an increase in peripheral insulin responsiveness in the two most anemic groups while a slight leftward shift was suggestive of an increase in insulin sensitivity in all three anemic groups. Hepatic insulin sensitivity and responsiveness were unaffected by IDA. We conclude that increased glucose utilization rates in IDA rats are due primarily to an increase in peripheral insulin responsiveness. PMID- 8460686 TI - Local bone injections of LPS and M-CSF increase bone resorption by different pathways in vivo in rats. AB - We investigated the local in vivo action of lipopolysaccharide (LPS), a potent monocyte activator, and of macrophage colony-stimulating factor (M-CSF), a hemopoietic growth factor influencing monocyte differentiation, on bone resorption in normal female 8-wk-old rats. LPS (2 injections of 0.5 microgram), M CSF (2 injections of either 12.5, 25, 100, or 500 ng), or vehicle was injected into bone marrow space through a thin catheter implanted, under hydrochloride anesthesia, in the distal end of the right femur. Histomorphometry was performed after staining of the tartrate-resistant acid phosphatase (TRAP). The number of osteoclasts and of TRAP-positive marrow cells (considered as osteoclast precursors) were counted in the secondary spongiosa. LPS caused a 3-fold increase in osteoclast surface, a 4.5-fold increase in the number of osteoclasts, but no change in the number of TRAP-positive marrow cells. M-CSF induced a striking dose dependent biphasic effect on the number of TRAP-positive marrow cells and on bone resorption (no change with the lowest or with the highest concentrations, although the two intermediate doses significantly increased resorption surfaces and the number of osteoclasts). Our results demonstrate a local in vivo effect of LPS and of M-CSF on bone resorption and suggest that these substances act at different stages of osteoclast development and function. PMID- 8460687 TI - Thyroidal vascular responsiveness to parasympathetic stimulation is increased in hyperthyroidism. AB - It has been suggested that thyroid blood flow (TBF) is regulated by both parasympathetic and sympathetic nerves. Because thyroxine (T4) pretreatment increases the sensitivity of the thyroid to the effects of thyrotropin, the present study was conducted to determine whether T4 pretreatment can also sensitize the thyroid to the effect of parasympathetic stimulation on TBF. Untreated or T4-pretreated rats were anesthetized, and both superior laryngeal nerves (SLN) were transected. TBF was continuously monitored by laser Doppler flowmetry (LDF), and thyroid vascular conductance (TVC) was also determined by the microsphere technique. Stimulation of the SLN had no effect on TBF or TVC in untreated rats when measured by LDF or microspheres. In contrast, stimulation of the SLN after T4 pretreatment increased TBF by 65 +/- 21% over prestimulus levels as measured by LDF. TVC was also increased significantly (P < 0.05) in these rats compared with TVC in a nonstimulated T4-pretreated group. To examine the role of muscarinic receptor activation in the mediation of these increases in TVC, T4 pretreated rats were given saline or atropine prior to SLN transection. Stimulation of the SLN in T4-pretreated rats given saline increased TVC significantly (P < 0.05) compared with TVC in the nonstimulated saline-treated or atropine-treated group. In contrast, TVC in the stimulated group given saline was not significantly different from the group that was stimulated after atropine injection. Our results suggest that the thyroidal vascular responsiveness to parasympathetic stimulation is increased in the hyperthyroid condition. PMID- 8460688 TI - Ouabain is secreted by the adrenal gland in awake dogs. AB - Ouabain has been identified in the plasma and adrenal glands of several mammals, including humans. To investigate possible adrenal secretion of ouabain in vivo, at rest, and in response to acute blood volume changes, we prepared trained adult dogs (n = 10) with splenectomy and unilateral adrenal venous (AV) cannulation. Two days later, after an overnight fast, dogs had either 1) 20% hemorrhage (hem) or 2) 20% blood volume expansion (exp; 6% Dextran 70, 0.9% NaCl) in random order. In AV and arterial plasma (ART), ouabain was measured by a ouabain-specific immunoassay, and cortisol and aldosterone were measured by radioimmunoassay. ART and AV ouabain concentration did not change after hem or exp [P = not significant (NS)]. In 94 of 97 paired samples, the concentration of ouabain in AV was greater than that in ART (Wilcoxon, P < 0.001), and the mean ouabain concentration was greater in AV (756.4 +/- 85.7 pmol/l) than ART (235.4 +/- 18.5 pmol/l; P < 0.001). The mean AV-to-ART ouabain concentration ratio was 5.7 +/- 1.29. Adrenal secretion of ouabain was not influenced by hem or exp (analysis of variance, P = NS). Adrenal secretion of cortisol and aldosterone increased after hem (P < 0.05) and was unaltered by exp (P = NS). This study demonstrates that ouabain is secreted by the adrenal gland in the awake dog. However, adrenal ouabain secretion and arterial blood ouabain are not altered by acute hem or exp. PMID- 8460689 TI - Acute effects of ethanol on hepatic endocytosis and processing of insulin in perfused rat liver. AB - This study utilizes the perfused rat liver combined with subcellular fractionation and compartmental analysis to investigate the effects of ethanol on hepatic uptake, endocytosis, and processing of insulin. At 4 min after the start of a 2-min pulse of radiolabeled insulin, increasing ethanol concentrations progressively inhibited insulin uptake by the liver (57% at 50 mM ethanol). Subcellular fractionation of the perfused livers showed a progressive shift in distribution from a predominantly endosomal location (control) to a bimodal distribution between endosomes and plasma membrane. This could be largely accounted for by a specific reduction in the endosome-associated insulin. Binding studies showed no changes in the binding properties of the plasma membrane insulin receptor. Compartmental analysis of the perfusate efflux curves confirmed the lack of effect of ethanol on the binding constants but showed a significant decrease in the endocytic rate constant (50%) together with an increase in the retroendocytic rate constant (33%). Simulation studies with the compartmental model showed that these changes could account for the observed decrease in uptake by the liver. No changes were found in the subsequent endocytic degradation of insulin. PMID- 8460690 TI - Respiratory, ionic, and functional effects of succinate esters in pancreatic islets. AB - The methyl esters of succinic acid were introduced a few years ago as new potent insulin secretagogues. In the present study, they were found to increase O2 uptake by rat islets incubated in the absence or presence of D-glucose; to decrease 86Rb outflow from prelabeled islets; to stimulate biosynthetic activity in the islets, with a preferential effect on the synthesis of proinsulin; to inhibit 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca2+ but to augment 45Ca net uptake and to cause a biphasic stimulation of 45Ca outflow in islets incubated or perifused in the presence of extracellular Ca2+; and to evoke a biphasic stimulation of insulin release. The insulinotropic action of these methyl esters coincided with a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration, was concentration related in the 2-10 mM range, failed to be duplicated by succinic acid, displayed both Ca2+ dependency and resistance to a lowering of extracellular pH, and was operative in the absence of D-glucose whether or not the islets were stimulated by non-nutrient secretagogues. It is concluded that the respiratory, cationic, biosynthetic, and secretory responses of the islets to succinate methyl esters display the characteristic features usually encountered in the process of nutrient-stimulated insulin release. PMID- 8460691 TI - Metabolic effects and fate of succinate esters in pancreatic islets. AB - The metabolic effects and the catabolism of succinate methyl esters were examined in rat pancreatic islets. The esters augmented 14CO2 production from islets prelabeled with L-[U-14C]-glutamine but inhibited NH4+ output, suggesting that they do not activate glutamate dehydrogenase. They decreased 14CO2 output from islets prelabeled with [U-14C]palmitate. They had little effect on the oxidation of exogenous D-[3,4-14C]glucose, D-[2-14C]glucose, D-[6-14C]glucose, or D-[1 14C]glucose, suggesting unaltered ratio between the input of acetyl residues and four- or five-carbon metabolites, such as succinate, into the Krebs cycle. By following the fate of both [1,4-14C]succinate dimethyl ester and [2,3 14C]succinate dimethyl ester, data were obtained to indicate that succinate is efficiently formed from the ester and further metabolized, leading to the generation of 14C-labeled acidic metabolites including pyruvate and L-lactic acid, CO2, and amino acids. It is proposed that a concerted increase of both succinate and acetyl residue influx into the Krebs cycle accounts for the increase in O2 uptake caused by the succinate methyl esters and, hence, for stimulation of both pro-insulin biosynthesis and insulin release. PMID- 8460692 TI - Pancreatic beta-cell function and glucose metabolism in human segmental pancreas and kidney transplantation. AB - beta-Cell function and glucose metabolism were studied in eight insulin-dependent diabetic recipients of combined segmental pancreas and kidney transplant with peripheral insulin delivery (Px), in eight nondiabetic kidney-transplant individuals (Kx), and in eight normal subjects (Ns) after three consecutive mixed meals. All subjects had normal fasting plasma glucose, but increased basal levels of C-peptide were demonstrated in the transplant groups (P < 0.05 relative to Ns). Postprandial hyperglycemia was increased 14% in Kx and 32% in Px (P < 0.05), whereas compared with Ns postprandial C-peptide levels were increased three- and twofold, respectively, in Kx and Px (P < 0.05). Compared with Ns basal insulin secretion rate (combined model) was increased 2-fold in Kx and 1.4-fold in Px (P < 0.05). Maximal insulin secretion rate was reduced 25% in Px compared with Kx (P < 0.05) but not different from that of Ns (P NS). Also, maximal insulin secretion rate occurred later in Px than in controls (Tmax: Px 50 min, Kx 30 min, and Ns 32 min; P < 0.05). The total integrated insulin secretion was increased 1.4-fold in Px compared with Ns (P < 0.05) but decreased 1.4-fold compared with Kx (P < 0.05). Fasting and postprandial proinsulin-to-C-peptide molar ratios were inappropriately increased in Px compared with Kx and Ns. Basal hepatic glucose production was increased 43% in Px and 33% in Kx compared with Ns (P < 0.05). Postprandial total systemic glucose appearance was similar in all three groups, whereas peripheral glucose disposal was 15% reduced in Px (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460693 TI - Determinants of decline in resting metabolic rate in aging females. AB - We considered the association of several metabolic and lifestyle variables as modulators of the decline in resting metabolic rate (RMR) and fat-free weight (FFW) in 183 healthy females (18-81 yr). RMR showed a curvilinear decline with age, which was significant in women aged 51-81 yr but not in women aged 18-50 yr. FFW showed a curvilinear decline with age, which was significant (P < 0.01) in women 48-81 yr but not in women 18-47 yr. The decline in RMR was primarily associated with the loss of FFW (r2 = 72%), whereas the decline in FFW was explained primarily by differences in maximal O2 consumption (VO2max), age, leisure time physical activity, and dietary protein intake (total r2 = 46%). We conclude that RMR and FFW showed a curvilinear decline with age which was accelerated beyond the middle-age years. Second, the age-related decline in RMR was primarily associated with the loss of FFW. Third, the loss of FFW was partially related to a decrement in VO2max and nutritional factors. Therapeutic interventions designed to increase VO2max by elevating physical activity may preserve fat-free weight and thus offset the decline of RMR in aging women. PMID- 8460694 TI - Two-compartment model of acute stimulation of aldosterone secretion in vivo by angiotensin II. AB - Sheep with a cervical adrenal autotransplant were used to establish the relationship between acute change in angiotensin II (ANG II) concentration and acute change in aldosterone secretion rate (ASR). The kinetics of 131I-labeled ANG II and unlabeled ANG II across the adrenal were consistent with distribution within a two-compartment model. ASR was found to be a linear function of the ANG II concentration predicted to occur in the second compartment, indicating that acute change in ASR is determined to a large degree by the rate of exchange of ANG II between the first and second compartments. The time required for ANG II concentration to reach 50 and 95% of steady state was estimated to be approximately 5 and 45 min, respectively. The time course for agonist distribution within the adrenal may be an important factor to consider in both the design and interpretation of experimental studies that involve the stimulation (or inhibition) of adrenocortical cells. PMID- 8460695 TI - Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey. AB - One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH. PMID- 8460696 TI - Determinants of intrabolus pressure during esophageal peristaltic bolus transport. AB - Previous manometric studies of esophageal fluid bolus transport in humans have generally ignored the hydrodynamic distinction between intrabolus pressure and pressure within the lumen-occluded, contracting esophageal segment. In this study we obtained concurrent esophageal videofluoroscopic and intraluminal manometric recordings in supine normal volunteers using different bolus volumes and viscosities and abdominal compression. Intrabolus pressure increased with bolus volume, viscosity, and abdominal compression. Esophageal diameter increased with larger bolus volumes, and this increase was correlated with increases in intrabolus pressure. Intrabolus pressure was highest in the bolus tail. Peak intraluminal pressures > 20 mmHg above basal intrabolus pressure almost invariably were associated with effective peristalsis, whereas values of this pressure differential < 20 mmHg frequently were associated with ineffective peristalsis and retrograde bolus escape. Intrabolus pressure can serve as an important indicator of the forces resisting peristaltic transport and the occurrence of ineffective bolus transport. PMID- 8460697 TI - Protective action of oral N-acetylcysteine against gastric injury: role of hypertonic sodium. AB - N-acetylcysteine (NAC), when administered orally as a 20% solution, is a potent protective agent against gastric injury in the rat stomach induced by absolute ethanol. The present study was undertaken to define the means by which this protection is mediated. The notion that NAC acts as a glutathione precursor was excluded when N-acetylserine (NAS) was noted to be equally protective against alcohol injury. The NAS molecule contains a hydroxyl moiety at the site where NAC contains a sulfhydryl. To orally administer 20% NAC at a neutral pH, NaOH is added to the free acid form to keep NAC in solution. We determined by titration that a sodium concentration of 1.2 M results. Thus it became apparent that the protective effect of NAC might be mediated through the sodium employed to titrate NAC. Accordingly, we examined various sodium salts and assessed their relative protective effects against alcohol injury. Both sodium acetate and sodium chloride in 1 M solutions were found to be equally effective in preventing alcohol injury with the same efficiency as 1 M sodium solutions of NAC and NAS, excluding the acetate portion of NAC and NAS as being of primary importance for protection to occur. Further study, using different concentrations of sodium chloride (i.e., 150-1,000 mM) revealed that the 1 M solution was most optimal in preventing alcohol injury. One molar sodium by itself and when administered as part of the NAC solution also prevented gastric injury by concentrated acid and base.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460698 TI - Effect of aging and bolus variables on pharyngeal and upper esophageal sphincter motor function. AB - Effect of aging, bolus volume, temperature, and consistency on the pharyngeal peristalsis, as well as the effect of aging on the upper esophageal sphincter (UES) resting pressure and its response to esophageal distension by air and balloon, were studied in 14 young and 12 healthy elderly volunteers. In both age groups there was no significant volume or temperature effect on amplitude, duration, or velocity of the pharyngeal peristalsis. Compared with water swallows, mashed potato swallows resulted in a significant increase in the amplitude and duration of the hypopharyngeal peristaltic pressure wave (P < 0.05). For water swallows, the amplitude and duration of the peristaltic pressure wave in the hypopharynx were significantly increased in the elderly compared with the young group (P < 0.01). UES resting pressure in the elderly measured 43 +/- 5 (SE) mmHg and was significantly less than that of the young (71 +/- 8 mmHg; P < 0.01). Magnitude of the UES pressure decrease because of esophageal distension by air, as well as magnitude of its pressure increase because of esophageal balloon distension, was similar among young and elderly. 1) Contrary to common expectations, the parameters of the pharyngeal peristaltic pressure wave do not deteriorate in the elderly in their seventh and eighth decade. 2) Compared with the young, hypopharyngeal pressure wave amplitude and duration are significantly increased in the elderly. This increase could be caused by an adaptation response to a pharyngeal outflow compromise. 3) Pharyngeal peristaltic pressure wave amplitude and duration, but not its velocity, are modulated by the bolus consistency. This modulatory mechanism is preserved in the elderly. 4) Although UES resting pressure is significantly decreased in the elderly, its pressure response to esophageal distension by air and balloon is preserved. PMID- 8460699 TI - Age-related differences in intestinal microvascular responses to low-flow states in adult and suckling rats. AB - We used in vivo videomicroscopic techniques to compare the intestinal microvascular responses of 8- to 12-wk-old adult rats with those observed in 8- to 12-day-old suckling rats. Changes in intestinal microarteriolar diameters and blood flow were measured during hemorrhage (5 and 10 ml/kg), hypoxia (10% O2 breathing environment), and hypothermia (surface cooling to 34 degrees C and 31 degrees C). Intestinal blood flow (as measured by optical Doppler velocimetry) was decreased by a similar amount in both adult and suckling rats during all three periods of stress. Large arteriolar diameter changes were also similar in adult and suckling rats. In contrast, there were substantial differences in the responses of the small premucosal arterioles. These premucosal arterioles selectively dilated in adult rats, suggesting a redistribution of blood flow toward the mucosa during each of the three periods of stress. These same microvessels failed to dilate in the suckling rats during each of the three periods of stress, suggesting that the intestinal microvasculature in the immature rat lacks vasodilator mechanisms that are active in the adult rat. We propose that altered microvascular control could make the developing intestine prone to mucosal damage during periods of decreased perfusion. PMID- 8460700 TI - Mechanism of bile acid-induced biliary lipid secretion in the rat: effect of conjugated bilirubin. AB - We have compared the effects of bilirubin and bilirubin ditaurate (BDT) on biliary phospholipid and cholesterol secretion in unanesthetized normal Wistar (NW) and Groningen Yellow (GY) Wistar rats under various experimental conditions. GY rats express a genetic defect in biliary secretion, but not in hepatic uptake, of various organic anions. Under physiological conditions, NW and GY rats showed similar biliary secretion rates of bile acids and of bilirubin, despite the fact that bilirubin concentrations in GY plasma were 25 times as high and in GY livers three times as high as in NW plasma and livers, respectively. Secretion of cholesterol and phospholipids was not impaired in GY rats under these conditions. Biliary secretion of intravenously injected BDT (3 mumol/100 g body wt) was delayed in eight-day bile-diverted GY rats and showed lower peak values when compared with NW rats. The inhibitory effects of BDT on phospholipid and cholesterol secretion paralleled these differences, being delayed and much less pronounced in GY rats. No overshoot in phospholipid or cholesterol secretion was observed when bilirubin output returned to preinjection values. Stimulation of [14C]choline-labeled phospholipid secretion after a bolus injection of taurochenodeoxycholic acid (1 mumol/100 g body wt) closely followed biliary bile acid concentration. Similarly, inhibition of labeled phospholipid secretion by BDT closely paralleled the biliary bilirubin concentration. Gel filtration studies (Sepharose 4B-CL) under micelle-preserving conditions demonstrated a specific interaction of BDT with biliary bile acids. The presented data indicate that conjugated bilirubin does not inhibit biliary lipid secretion via interaction with bile acids inside the hepatocyte.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460701 TI - Hepatic taurocholate uptake is electrogenic and influenced by transmembrane potential difference. AB - Uptake of the bile acid taurocholate by hepatocytes is coupled to Na+ influx. The stoichiometry of uptake, however, is uncertain, as is the influence of the transmembrane electrical potential difference (PD) on this process. In this study, we examined the relationship between taurocholate extraction and PD (measured using intracellular microelectrodes) in perfused liver, and we measured taurocholate-induced transport current in cultured hepatocytes using patch-clamp recording techniques. In the perfused liver under basal conditions, PD averaged 28.4 +/- 0.6 (SE) mV, and extraction of 1, 50, and 300 microM taurocholate was 0.95 +/- 0.02, 0.98 +/- 0.01, and 0.41 +/- 0.03, respectively. When the Na+ chemical gradient was decreased by replacing perfusate Na+ with choline, the membrane depolarized to -17.2 +/- 1.1 mV, and taurocholate extraction markedly decreased at all taurocholate concentrations (P < 0.01). When perfusate Na+ concentration was held constant at 137 mM, membrane depolarization induced by substitution of gluconate for perfusate Cl- (-17.9 +/- 0.6 mV) or Cl- for nitrate (-10.3 +/- 2.1 mV) significantly decreased extraction of 300 microM taurocholate. Abrupt exposure to taurocholate produced a concentration-dependent membrane depolarization in the presence of Na+, but not in its absence (P < 0.001). In cultured hepatocytes, exposure to 100 microM taurocholate produced an inward current of -0.056 +/- 0.016 pA/pF at a holding potential of -40 mV. This current was Na+ dependent, and it increased twofold as holding potential was changed from -20 to -50 mV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460702 TI - Cerebral-evoked potential responses following direct vagal and esophageal electrical stimulation in humans. AB - Cerebral evoked responses following direct electrical stimulation of the vagus and esophagus were compared in 8 epileptic subjects and with those recorded after esophageal stimulation in 12 healthy nonepileptic controls. Direct vagal stimulation was performed using a left cervical vagal pacemaker, which is used in the treatment of epilepsy. Esophageal stimulation was obtained with the use of an esophageal assembly incorporating two electrodes positioned 5 and 20 cm orad to the lower esophageal sphincter. Evoked potential responses were recorded with the use of 20 scalp electrodes. The evoked potential responses consisted of three distinct negative peaks and were similar with the use of either vagal or esophageal stimulation. The measured conduction velocity of the afferent response was 7.5 m/s in epileptic subjects and 10 m/s in healthy controls, suggesting that afferent conduction is through A delta-fibers rather than slower C afferent fibers. We conclude that the cortical-evoked potential responses following esophageal electrical stimulation are comparable to direct electrical stimulation of the vagus nerve and involve mostly A delta-fibers. This approach provides a method for the assessment of vagal afferent gastrointestinal sensory pathways in health and disease. PMID- 8460703 TI - Distribution and abundance of neutral endopeptidase (EC 3.4.24.11) in the alimentary tract of the rat. AB - The distribution of neutral endopeptidase (NEP; EC 3.4.24.11) was examined in the alimentary tract of the rat. Immunoreactive NEP and NEP mRNA were localized to epithelial cells of the small intestine and to muscle cells in the stomach, small intestine, and colon by immunohistochemistry and in situ hybridization histochemistry. NEP antisera recognized a protein on Western blots of membranes from gastric, jejunal, and colonic mucosa and gastric muscle with an electrophoretic mobility identical to that of recombinant human NEP (approximately 95 kDa). An antisense cRNA probe to NEP hybridized to RNA of approximately 3.5 kb and approximately 6.5 kb, corresponding to the primary transcripts of rat NEP, on Northern blots of total RNA from the jejunal mucosa. NEP message was detected in mRNA from jejunal and colonic mucosa and gastric, jejunal, and colonic muscle using a ribonuclease protection assay. NEP enzymatic activity, assessed by DL-thiorphan-inhibitable degradation of glutaryl-Ala-Ala Phe-4-methoxy-2-naphthylamine, was highest in homogenates of jejunal mucosa (868 +/- 98 pmol.h-1 x micrograms protein-1) and was between 49- and 413-fold lower in other gastrointestinal tissues. The cellular origin of NEP in the gastric and colonic mucosa could not be determined. PMID- 8460704 TI - Vitamin A metabolism in rat liver: a kinetic model. AB - Vitamin A metabolism in the liver involves both hepatocytes and the nonparenchymal perisinusoidal stellate cells. To describe and quantitate the dynamic relationships between retinol in these cells and in plasma, we administered either chylomicrons labeled with [3H]retinyl esters or plasma containing [3H]retinol-retinol-binding protein-transthyretin to rats. Radioactivity and retinol masses were measured in plasma, liver, and isolated hepatocytes for 15 days; data were analyzed by model-based compartmental analysis. The resulting model predicts that: 1) approximately 20% of the total plasma turnover of retinol goes to the liver (vs. nonhepatic tissues) and approximately 20% of plasma retinol input is from liver (vs. nonhepatic tissues), 2) about one-half of the retinol recycling from plasma to liver is taken up by hepatocytes and about one-half by nonparenchymal cells, 3) retinyl esters in both cell types are derived preferentially from newly taken up retinol rather than from the main intracellular retinol pools, and 4) at least one-half of the retinol secreted by hepatocytes of rats consuming low levels of vitamin A is directly transferred to nonparenchymal cells. In addition, the data are compatible with the hypothesis that retinol-binding protein is the vehicle for transfer of retinol from hepatocytes to nonparenchymal stellate cells and between plasma and liver cells. PMID- 8460705 TI - Na(+)-dependent bile acid transport by hepatocytes is mediated by a protein similar to microsomal epoxide hydrolase. AB - A protein mediating hepatocyte sodium-dependent bile acid transport across the sinusoidal plasma membrane has been purified by immunoprecipitation with monoclonal antibody (MAb) 25D-1, which specifically recognizes this protein on the surface of intact hepatocytes (Ananthanarayanan et al. J. Biol. Chem. 263: 8338-8343, 1988). The function of this protein was further established by proteoliposome reconstitution (von Dippe et al. J. Biol. Chem. 265: 14812-14816, 1990). NH2-terminal amino acid sequence analysis and amino acid composition revealed this protein to be closely related to the enzyme microsomal epoxide hydrolase (mEH). Both proteins exhibited the same elution times on a reverse phase high-pressure liquid chromatography column, comigrated with an apparent molecular weight of 49,000 as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and possessed identical isoelectric points of 8.2. The MAb was capable of immunoprecipitating chromatographically purified mEH, as well as a protein derived from the sinusoidal plasma membrane that exhibited mEH activity comparable to that of the protein isolated from the endoplasmic reticulum. The subtilisin fragmentation patterns derived from chromatographically purified mEH and the MAb-precipitated plasma membrane protein were also identical. Hydropathy profile analysis of the amino acid sequence of mEH suggested the presence of four transmembrane domains. The results of these studies indicate that a protein that is involved in mediating sodium-dependent bile acid transport is closely related to mEH. PMID- 8460706 TI - Kinetic analysis of rat parotid gland muscarinic receptors in vivo: comparison with brain and heart. AB - (RR)- and (SS)-quinuclidinyl iodobenzilate enantiomers [(RR)- and (SS)-IQNB, active and inert, respectively] have been synthesized for quantitative evaluation of muscarinic acetylcholine receptor (mAChR) binding. Pharmacokinetic approaches have not been used previously to assess in vivo IQNB binding in nonexcitable tissues. We have applied this method to examine mAChRs in rat parotid gland in comparison to those in brain and heart. Short-term infusion studies in vivo showed that the "instantaneous" reversible binding of (RR)- and (SS)-IQNB was high in the parotid (greater nonspecific binding potential), intermediate in the heart, and lowest in cortex and cerebellum. Long-term bolus injection experiments showed that the parotid gland mAChRs possessed a binding potential for receptor specific sites (380), which was intermediate between that of parietal cortex (930) and cerebellum (10) and greater than that of heart (165). In vitro binding to plasma membranes was generally consistent with the in vivo findings. In aggregate, these studies show that mAChRs can be evaluated in vivo in a nonexcitable tissue with the use of stereospecific ligands and a pharmacokinetic approach. The data suggest that IQNB, a mAChR antagonist, can identify characteristics of specific binding sites, which may reflect tissue differences. PMID- 8460707 TI - Effect of dietary lipid peroxides on metabolism of serum chylomicrons in rats. AB - We have found that in rats the peroxide content of chylomicrons (CM) is determined by the lipid peroxide concentration in the diet, indicating that dietary lipid peroxides are incorporated into the lymph CM. Moreover, these incorporated lipid peroxides influence the normal CM metabolism. When radiolabeled CM were injected into rats, there was no difference in the initial plasma removal between CM prepared from oil with low peroxide content (control CM) and CM prepared from oil with high peroxide content (oxidized CM). However, the tissue distribution of the labels indicated that the hepatic uptake of CM decreased with increasing lipid peroxide content of CM. At 10 min after injection of CM, liver uptake of cholesterol label was 48.39 +/- 3.08% for control CM and 31.41 +/- 10.73% for oxidized CM. Vitamin E enrichment of control CM increased their hepatic uptake to 61.07 +/- 0.83%. Additionally, binding of oxidized CM to the heart endothelium increased from 2.55 to 3.60% compared with binding of control CM. When the hydrolysis of control and oxidized CM by endothelial lipoprotein lipase (LPL) was tested in a heart perfusion system, we found that after 30 min, 56.51 +/- 5.81% of control and 76.82 +/- 1.75% of oxidized CM were not hydrolyzed and remained in the perfusate. Thus our results indicate that the altered metabolism of oxidized CM may be related to a reduced hydrolysis rate by endothelial LPL. PMID- 8460708 TI - Oleic acid-induced mucosal injury in developing piglet intestine. AB - A role for luminal nutrients, in particular products of lipid digestion, in the pathogenesis of mucosal injury to developing intestine has been postulated. We evaluated changes in mucosal permeability and light and electron microscopic histology induced by luminal perfusion with the long-chain fatty acid oleate in developing piglet intestine as a function of age and concentration of the fatty acid. 51Cr-labeled EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets during sequential perfusion with saline control (20 min); 0, 1, 5, and 10 mM oleic acid/10 mM taurocholate in saline (20 min); and normal saline (60 min). The jejunum of piglets < or = 2 wk showed significantly greater increases in mucosal permeability compared with 1-mo old animals after perfusion with oleic acid. This effect was dependent on the luminal concentration of the fatty acid and was associated with mucosal injury evident under light and electron microscopy. In contrast, the overall response in ileum was more attenuated compared with jejunum. Thus oleic acid, a common dietary fatty acid, induces dose- and age-dependent injury in developing piglet intestine. Investigation of the mechanisms of this injury may provide the basis for dietary modifications directed at decreasing the risk of mucosal injury during enteral feeding in neonatal intestine. PMID- 8460709 TI - Control of gastric corpus chromogranin A messenger RNA abundance in the rat. AB - Enterochromaffin-like cells in the corpus mucosa of the stomach produce histamine in response to gastrin; chromogranin A (CGA) is often used as a morphological marker for these cells, but its functional significance in the gastric mucosa is largely unknown. We have examined whether CGA mRNA abundance in the rat corpus is controlled by endogenous gastrin. In rats fasted for up to 48 h, there was a progressive decline in plasma gastrin and CGA mRNA; refeeding of fasted rats produced a prompt increase in plasma gastrin and an increase in CGA mRNA that was significant after 4 h. Treatment of fasted rats with omeprazole to inhibit acid secretion increased plasma gastrin and CGA mRNA levels. The increased CGA mRNA associated with omeprazole or refeeding was reversed by treatment of rats with the gastrin/cholecystokinin B antagonist CI-988 and gastrin antibody, respectively. The results suggest that CGA production in enterochromaffin-like cells of the rat stomach is part of the functional response of these cells to circulating gastrin. PMID- 8460710 TI - Pertussis toxin attenuates platelet-activating factor-induced pulmonary hemodynamic alterations in pigs. AB - To determine whether platelet-activating factor (PAF)-induced release of cyclooxygenase products might be dependent on G proteins in vivo, we administered pertussis toxin (PTX) (9.7-10.0 micrograms/kg iv) to conscious pigs approximately 48 h before bolus infusions of PAF (10 ng/kg). Autoradiography of ADP-ribosylated lung cell membrane proteins from PTX-treated pigs demonstrated marked reduction in the amount of radiolabel ([32P]NAD) incorporated, indicating that PTX induced ADP-ribosylation of G proteins in vivo. PAF, infused at hourly intervals from 0-4 h, caused increases in plasma concentrations of thromboxane B2 (TxB2) concomitant with pulmonary hypertension and vasoconstriction in anesthetized pigs. These physiological changes were blocked or markedly attenuated by indomethacin, indicating they were dependent on cyclooxygenase products. In PTX-treated pigs, the PAF-induced pulmonary hypertension and vasoconstriction were modestly attenuated, whereas the increases in plasma TxB2 were markedly attenuated. PTX prevented PAF-induced aggregation of platelets in vivo as evidenced by blockade of thrombocytopenia. However, in vitro, PAF-induced aggregation of platelets was independent of PTX. Moreover, incubation of platelet-rich plasma with 50 microM PAF failed to increase TxB2 levels. These findings suggested that a PTX-sensitive cell other than the platelet was responsible for triggering release of TxA2 and thrombocytopenia in vivo. We conclude that PAF-induced release of TxA2, pulmonary vasoconstriction, and thrombocytopenia in anesthetized pigs are dependent on a PTX-sensitive G protein; however, the residual hemodynamic effects indicate involvement of a PTX-insensitive G protein, or alternatively, G protein independent pathways. PMID- 8460711 TI - Activation of tracheal smooth muscle responsiveness by fMLP-treated HL-60 cells and neutrophils. AB - We assessed the effects of cultured human promyelocytic leukemia (HL-60) cells and polymorphonuclear leukocytes (neutrophils) isolated from peripheral human blood on tracheal smooth muscle responsiveness in 40 male Hartley guinea pigs. Undifferentiated HL-60 cells (16-25 passages) were activated in vitro by incubation with 1 microM f-Met-Leu-Phe (fMLP), and force of contraction was measured isometrically using an in situ preparation of tracheal smooth muscle. Increasing concentrations of acetylcholine (ACh; 10(-10) to 10(-6) mol/cm2 tracheal surface) were applied topically to the epithelial surface pretreated with 4 x 10(6) fMLP-activated HL-60 cells, 4 x 10(6) fMLP-activated neutrophils, 4 x 10(6) sham-activated HL-60 cells, fMLP+vehicle, or vehicle control. Topical application of fMLP-activated HL-60 cells caused a maximum active tension (AT) of 1.13 +/- 0.2 g/cm after 5 min; fMLP-activated neutrophils, sham-activated HL-60 cells, or fMLP+vehicle had no effect. The fMLP-activated HL-60 cells also caused substantial augmentation of tracheal contraction to ACh (P < 0.05 vs. sham activated cells for all concentrations > 10(-9) mol/cm2). Although fMLP treatment caused 247 +/- 28% increase from baseline level in O2-. production, neither direct contraction nor augmentation of muscarinic stimulation was demonstrated after topical application of 4 x 10(6) neutrophils. In 12 other preparations, fMLP-activated HL-60 cells were pretreated with either 10 microM indomethacin (Indo) or 100 microM A63162, a 5-lipoxygenase inhibitor. Pretreatment with Indo caused complete blockade of direct tracheal contraction and 88 +/- 13% blockade of muscarinic augmentation; there was no effect after A63162.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460712 TI - Biphasic glucocorticoid regulation of pulmonary SP-A: characterization of inhibitory process. AB - Pulmonary surfactant, which is necessary for normal lung function, is under both developmental and hormonal regulation. Glucocorticoids induce all components of surfactant and have a unique biphasic effect on surfactant protein A (SP-A), either stimulating or inhibiting accumulation in cultured fetal lung depending on dose and time of exposure. In this study we further characterized glucocorticoid inhibition of SP-A in cultured explants of human fetal lung. Decreased content of SP-A mRNA was the dominant response to dexamethasone added either early or later during culture. Inhibition occurred at < or = 1 nM dexamethasone on prolonged exposure, was blocked by RU 486, and was observed with other glucocorticoids but not sex steroids. When cortisol was removed from the culture medium, inhibition was rapidly reversed. The immediate inhibitory effect of 100 nM dexamethasone on SP-A mRNA content was completely blocked in the presence of cycloheximide. SP-A gene transcription, measured by nuclear elongation assay, was decreased by 60% after 4- to 8-h exposure to 100 nM dexamethasone. Stability of SP-A mRNA, determined both by addition of actinomycin D and by label-chase experiments, was transiently decreased immediately after adding dexamethasone (t1/2 approximately 3 h). In tissue treated with dexamethasone for > or = 8 h the stability of SP-A mRNA in control and treated explants was not different (t1/2 approximately 8 h). Our findings indicate that inhibition of SP-A is the dominant response to glucocorticoid. This effect is receptor mediated and apparently involves induction of a labile protein(s) that decreases gene transcription and transiently reduces mRNA stability. PMID- 8460713 TI - Increased pulmonary vascular permeability in rats with biliary cirrhosis: role of thromboxane A2. AB - Rats with liver cirrhosis exhibit arterial hypoxemia and loss of hypoxic pulmonary vasoconstriction similar to some patients with end-stage liver disease. We hypothesized that the pulmonary circulatory dysfunction in cirrhosis results from vascular endothelial cell injury and interstitial lung edema. To investigate this hypothesis, we compared the extravascular lung albumin leak, lung ultrastructural changes, and tissue eicosanoid levels in control and cirrhotic rats. In comparison to sham-operated controls, rats with biliary cirrhosis, 6 wk after ligation of the common bile duct, had increased lung albumin leak index (1.46 +/- 0.12 vs. 0.80 +/- 0.04, P < 0.001) and bloodless lung wet-to-dry weight ratio (4.94 +/- 0.05 vs. 4.78 +/- 0.03, P < 0.05). Electron-microscopic sections of lungs from cirrhotic rats demonstrated infiltration with intravascular macrophage-like cells, endothelial cell injury, and interstitial edema. In addition, lung tissue thromboxane B2 was significantly increased in cirrhotic rats, and pretreatment with a thromboxane synthase inhibitor, dazoxiben, reduced lung thromboxane B2 level and attenuated extravascular lung albumin leak (control 1.03 +/- 0.07, cirrhotic 2.29 +/- 0.06, cirrhotic plus dazoxiben, 1.57 +/- 0.17). In contrast, WEB 2086, a platelet-activating factor antagonist, had no effect on lung albumin leak. We conclude that pulmonary vascular permeability is increased in rats with biliary cirrhosis and that thromboxane A2 contributes to the pulmonary circulatory abnormalities in cirrhosis. PMID- 8460714 TI - Phospholipase A2 in alveolar type II epithelial cells: biochemical and immunologic characterization. AB - The enzyme phospholipase A2 (PLA2) catalyzes phospholipid hydrolysis and is thought to play important roles in surfactant synthesis and in the generation of lipid mediators, including eicosanoids and platelet-activating factor. This study sought to characterize PLA2 in rat type II pneumocytes by biochemical and immunologic means. Type II cells were found to contain an alkaline-active, Ca(2+) dependent PLA2 activity predominantly localized to cytosol fraction. This activity preferred phospholipids containing arachidonate in the sn-2 position and phosphatidylethanolamine (PE) over phosphatidylcholine (PC); it was active at physiologically relevant Ca2+ concentrations and was resistant to dithiothreitol. These biochemical features were suggestive of a high-molecular-weight form of PLA2, and immunoblot analysis of type II cell extracts indeed detected a 97-kDa protein corresponding to a high-molecular-weight PLA2, but no low-molecular weight pancreatic-type enzyme. Human A549 cells, which share certain features with type II cells, contained a similar PLA2 activity and immunoreactive protein. By contrast, whole rat lung cytosol contained both a 97-kDa PLA2 and a 14-kDa pancreatic-type PLA2, but its activity was typical of the latter in that it lacked sn-2 specificity for arachidonate and was inhibited by dithiothreitol. These results indicate that rat type II as well as human A549 epithelial cells contain a high-molecular-weight PLA2, for which mounting evidence suggests an important role in physiological and pathophysiological situations. PMID- 8460715 TI - ACh release from horse airway cholinergic nerves: effects of stimulation intensity and muscle preload. AB - This study was conducted to determine the effects of stimulation parameters and muscle preload on acetylcholine (ACh) release induced by electrical field stimulation (EFS) of horse airway cholinergic nerves. Trachealis strip bundles were prepared and suspended in 2-ml tissue baths. The tissues were stimulated three to five times for 30 min each. Increasing frequency (0.5-16 Hz) and voltage (5-20 V) increased ACh release; increasing pulse duration (0.5-3 ms) had only a minor effect. Alterations in muscle preload (2-20 g) had no effect on ACh release. ACh release was fairly constant for up to five repeated stimulation periods with the same EFS parameters. Stimulation of the tissues for 15 min released the same amount of ACh as 30 min if the amount was expressed as picomoles per gram per minute, suggesting that ACh release rate was constant during the 30-min period of stimulation. Atropine (10(-6) M) potentiated the release of ACh four- to fivefold, presumably by removing the autoinhibitory effect of ACh on the cholinergic nerves. Tetrodotoxin (10(-6) M) abolished the EFS-induced ACh release. PMID- 8460716 TI - Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity. AB - Chronic exposure to asbestos fibers results in fibrotic lung disease. The distal pulmonary epithelium is an early target of asbestos-mediated injury. Local plasmin activity may be important in modulating endoluminal inflammatory responses in the lung. We studied the effects of asbestos exposure on cell mediated plasma clot lysis as a marker of pericellular plasminogen activation. Exposing human bronchial epithelial (HBE) cells to 100 micrograms/ml of asbestos fibers for 24 h resulted in increased plasma clot lysis. Fibrinolytic activity was augmented in a dose-dependent fashion, was not due to secreted protease, and occurred only when there was direct contact between the plasma clot and the epithelial monolayer. Further analysis showed that asbestos exposure increased HBE cell-associated urokinase-type plasminogen activator (uPA) activity in a time dependent manner. The increased cell-associated PA activity could be removed by acid washing. The increase in PA activity following asbestos exposure required new protein synthesis because it was abrogated by treatment with either cycloheximide or actinomycin D. Therefore, asbestos exposure increases epithelial mediated fibrinolysis by augmenting expression of uPA activity at the cell surface by mechanisms that require new RNA and protein synthesis. These observations suggest a novel mechanism whereby exposure of the distal epithelium to inhaled particulates may result in a chronic inflammatory response that culminates in the development of fibrotic lung disease. PMID- 8460717 TI - Role of Ca2+ entry in the modulation of airway tone by hypoxia. AB - To evaluate the cellular mechanisms involved in hypoxic relaxation of airway smooth muscle, we investigated the effects of hypoxia on the behavior of third- and fourth-order porcine bronchial rings contracted with either carbachol or KCl. In one series of experiments, hypoxia (95% N2-5% CO2) was imposed and rings were then exposed to increasing concentrations of carbachol or KCl. In separate experiments, rings were first contracted with carbachol (10(-6) M) or KCl (40 mM) and were then exposed to solutions bubbled with decreasing concentrations of O2. The CO2 concentration was maintained constant at 5% in all experiments. The initial magnitude of KCl-induced but not carbachol-induced contractions was profoundly reduced by 95% N2-5% CO2. The sensitivity of the airway to carbachol was unchanged. In rings precontracted with either carbachol or KCl, hypoxia caused similar losses of airway smooth muscle tone in a reversible and concentration-dependent manner. The effects of hypoxia were independent of the presence of an intact epithelium and were not inhibited by the cyclooxygenase inhibitor indomethacin (5 microM), the soluble guanylate cyclase inhibitor methylene blue (50 microM), or the beta-adrenoceptor antagonist propranolol (1 microM). The impairment by hypoxia of the initiation phase of KCl-induced contractions and of the maintenance phase of both KCl- and carbachol-induced contractions, but not the initiation phase of carbachol-induced contractions, suggests that changes in O2 tension modulate airway tone by altering the entry of extracellular calcium into the airway smooth muscle. PMID- 8460718 TI - Cell-specific posttranslational processing of the surfactant-associated protein SP-B. AB - Pulmonary surfactant-associated protein B (SP-B) is a 9-kDa lung-specific protein expressed in alveolar epithelial type II cells and Clara cells. The protein markedly increases the surface activity of phospholipids and is an active component in some surfactants in clinical use. SP-B is produced from a 43-kDa precursor protein by proteolytic cleavage of flanking regions from both the NH2- and COOH-terminal ends of the active protein. In this study we have compared the nature of the posttranslational processing of the SP-B precursor in type II cells and in a heterologous cell line transfected with the SP-B precursor. We found that isolated type II cells produce the 9-kDa form of SP-B from the precursor through a series of intermediates detectable in the cell lysates. In contrast Chinese hamster ovary cells stably transfected with the full-length human SP-B precursor produce the precursor and a 26-kDa intermediate but not the 9-kDa protein. The precursor protein in both cell types is glycosylated with NH2-linked sugars. Our results suggest there is cell specificity in the posttranslational processing of the SP-B precursor. PMID- 8460719 TI - Asymmetric effects of H2O2 on alveolar epithelial barrier properties. AB - The effects of H2O2 on active ion transport and resistance to passive solute flow were studied utilizing rat alveolar epithelial cell monolayers cultured on permeable supports. Type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered Ringer solution. These monolayers have a high transepithelial resistance (> 2,000 omega.cm2) and actively transport Na+ from apical fluid. H2O2 (0-100 mM) was then delivered to either apical or basolateral fluid. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against H2O2 injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ; an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results indicated that H2O2 decreased Isc and R gradually in a dose-dependent manner. The effective concentration of apical H2O2 at which Isc (or R) was decreased by 50% at 1 h (ED50) was approximately 4 mM. However, basolateral H2O2 exposure led to ED50 for Isc (and R) of approximately 0.04 mM. Inhibition of cellular catalase yielded ED50 for Isc (and R) of approximately 0.4 mM when H2O2 was given apically, while ED50 for basolateral exposure to H2O2 did not change in the presence of ATAZ. The rate of H2O2 consumption in apical and basolateral bathing fluids was the same, while cellular catalase activity rose gradually with time in culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460720 TI - Peptidase inhibitors reverse steroid-induced suppression of neutrophil adhesion in rat tracheal blood vessels. AB - Exposure of the tracheal mucosa of rats to capsaicin evokes neurogenic inflammation, one manifestation of which is the adherence of neutrophils to the endothelium of venules. In the present experiments, with the use of aerosolized capsaicin, we determined whether this neutrophil adhesion is inhibited by dexamethasone and whether the effect of dexamethasone can be reversed by inhibiting endopeptidase 24.11 (neutral endopeptidase, NEP) and kininase II (angiotensin-converting enzyme, ACE), which degrade the neuropeptides that mediate neurogenic inflammation. Adult male pathogen-free F344 rats were treated for 2 days with dexamethasone or with vehicle (controls) and were then exposed for 2 min to aerosolized capsaicin. Neutrophils adhering to the endothelium of venules in tracheal whole mounts were stained histochemically for myeloperoxidase and then counted. Sites of increased vascular permeability were localized with Monastral blue. In the control rats, aerosolized capsaicin (10(-8)-10(-3) M) increased in a concentration-dependent fashion the number of adherent neutrophils and the amount of Monastral blue labeling of blood vessels. Dexamethasone in doses of 0.5, 1, 2, or 4 mg.kg-1.day-1 reduced by 49 63, 80, and 93%, respectively, the number of adherent neutrophils in capsaicin-exposed rats and caused similar reductions in the amount of Monastral blue labeling. When given alone, neither phosphoramidon, an inhibitor of NEP, nor captopril, an inhibitor of ACE, completely reversed this effect of dexamethasone, but when the two drugs were administered together, adherent neutrophils were as numerous in the dexamethasone-pretreated rats (112 +/- 9 neutrophils/mm2) as in controls (109 +/- 10 neutrophils/mm2). The amount of Monastral blue labeling was also similar in these two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460721 TI - "Getting real" about HIV in adolescents. PMID- 8460722 TI - The control of iodine deficiency. PMID- 8460723 TI - The ethics of blinded HIV surveillance testing. PMID- 8460724 TI - Commentary: the new female condom--item 1 on a women's AIDS prevention agenda. AB - A US Food and Drug Administration (FDA) advisory panel has recommended that the female condom Reality be approved for contraception and acquired immunodeficiency syndrome (AIDS) prevention. Final FDA approval will mark the first official recognition of a woman-controlled method for protection against sexually transmitted disease. A female condom allows women to use just one method to respond to the twin anxieties of AIDS and unwanted pregnancy. In those couples in which the man refuses to wear a male condom, the availability of a female condom makes protection possible for the first time. Although the female condom has some advantages over the male condom--greater comfort for some women and men and nonreliance on male arousal--general population experience with the device is needed to achieve regular widespread use and hence effectiveness at population levels. The FDA still lags behind in responding to women's needs for information on AIDS and sexually transmitted disease. PMID- 8460725 TI - Commentary: condoms and HIV/STD prevention--clarifying the message. AB - In the United States and throughout the world, the majority of human immunodeficiency virus (HIV) infections are sexually transmitted. an estimated 12 million other sexually transmitted diseases occur annually in the United States. Avoiding sexual intercourse altogether or restricting sex to partners known to be uninfected will prevent infection; this needs to be promoted as the most effective strategy. Studies show that correct and consistent use of latex condoms is highly effective in preventing sexually transmitted HIV infection and other sexually transmitted diseases. The effectiveness of condoms depends on individual behavior leading to correct and consistent use. Further studies are needed to maximize the use and effectiveness of condoms for those who choose to be sexually active as well as to develop and evaluate other methods, particularly those more under the control of women. In the interim, our prevention message should be clear: When used correctly and consistently, condoms are highly effective; when used otherwise, they are not. PMID- 8460726 TI - Sentinel surveillance for HIV-2 infection in high-risk US populations. AB - OBJECTIVES: We conducted sentinel surveillance in persons practicing behaviors known to transmit retroviruses to determine the US presence and extent of human immunodeficiency virus type 2 (HIV-2). METHODS: Sentinel surveillance for HIV-2 was conducted by testing 31,533 anonymous blood specimens from patients at sexually transmitted disease clinics, injecting drug users at treatment centers, and clients at HIV counseling and testing sites in 14 US cities where West African immigrants often settle. Specimens were tested by HIV-1 and HIV-2 whole virus and synthetic peptide enzyme immunoassay and confirmed by HIV-1 and HIV-2 Western blots. RESULTS: Nearly 10% of 31,533 sera were positive for HIV-1. Two heterosexual Black male sexually transmitted disease patients were infected with HIV-2. One of the HIV-2 positive specimens did not cross-react on HIV-1 enzyme immunoassay screening. One client had antibodies consistent with malarial infection in West Africa; the other, who had syphilis, did not have antibodies to malaria or to any of 20 arboviruses present in Africa. CONCLUSIONS: Clinics serving clients from HIV-2 endemic areas should test persons practicing risk behaviors for both HIV-1 and HIV-2. Sentinel surveillance for HIV-2 serves as an early warning system for the possible spread of this virus in the United States. PMID- 8460727 TI - A method for identifying persons at high risk for sexually transmitted infections: opportunity for targeting intervention. AB - OBJECTIVES: The purpose of this study was to develop a method to identify persons at high risk for acquiring new sexually transmitted infections. METHODS: Computerized medical records from sexually transmitted disease clinics in Dade County, Florida, were used to conduct a retrospective cohort study. For all patients who visited in 1987, risk factors were identified for returning to the clinics within a year with a new sexually transmitted infection. Predictor variables were derived from the index visit and any visits in the year prior to the index visit. Logistic regression was used to develop a model that was applied to all patients who attended in 1989. RESULTS: Of 24,439 patients attending in 1987, 18.5% returned within a year with a new infection. Return rates were highest for 15- to 19-year-old Black males (31.8%). The highest odds ratios for returning were a diagnosis or treatment for an infection in the previous year and a diagnosis or treatment for infection at the index visit. The patients predicted to be at highest risk had a 39% return rate. There were as many new infections among the 2893 patients at highest risk as there were among the 13,326 patients at lowest risk. CONCLUSIONS: We developed a model that identifies persons at very high risk for sexually transmitted infection. These persons should be targeted for intensive intervention to reduce their risk. PMID- 8460728 TI - American adults' knowledge of HIV testing availability. AB - OBJECTIVES: Understanding client needs, knowledge, and preferences about services is necessary to ensure that human immunodeficiency virus (HIV) counseling and testing programs are accessible. This study addressed knowledge of HIV testing availability. METHODS: To study American adults' knowledge of HIV testing availability, we collected data during 1990 by random digit-dialing telephone surveys of adults residing in 44 states and the District of Columbia. RESULTS: Of the 81,557 persons who responded, almost two thirds identified medical doctors as a source of HIV testing. Fourteen percent identified public sites, and 12% said they didn't know where to go for HIV testing. Persons who were older, less educated, and had lower incomes were less likely to know where they could go for testing. Persons identifying public sites shared some characteristics with others who lacked adequate health care coverage. CONCLUSIONS: Physicians will be increasingly called upon to provide HIV counseling and testing to their patients. This may require additional training to provide effective, individualized, risk reduction messages about sexual and drug use behaviors. Even when persons have adequate information about availability, sociodemographic characteristics are likely to influence preferences for HIV counseling and testing. PMID- 8460729 TI - Changes in sexually transmitted disease rates after HIV testing and posttest counseling, Miami, 1988 to 1989. AB - OBJECTIVES: The effects of posttest counseling on acquisition of sexually transmitted diseases in patients at a large urban sexually transmitted disease clinic were studied. METHODS: Comparisons were made of the percentage of patients who had a positive gonorrhea culture (or any sexually transmitted disease) in the 6 months before and after human immunodeficiency virus (HIV) counseling and testing. RESULTS: For 331 patients counseled about a positive HIV test, the percentage with gonorrhea was 6.3 before and 4.5 after posttest counseling (29% decrease). For 666 patients counseled about a negative test, the percentage with gonorrhea was 2.4 before and 5.0 after posttest counseling (106% increase). With any sexually transmitted disease as the outcome, patients who tested positive for HIV had a 12% decrease and patients who tested negative had a 103% increase after counseling. CONCLUSIONS: HIV counseling and testing was associated with a moderate decrease in sexually transmitted diseases among patients who tested positive for the virus, but risk increased for patients who tested negative. This suggests a need to improve posttest counseling in this clinic and to assess the effects of counseling and testing in other clinics. PMID- 8460731 TI - A new approach to combatting iodine deficiency in developing countries: the controlled release of iodine in water by a silicone elastomer. AB - OBJECTIVES: Four hundred million people or more may be exposed to iodine deficiency worldwide, in developing countries in particular. Because of the practical problems with existing methods for the large-scale prevention of iodine deficiency, the authors developed a new approach to collective prophylaxis. METHODS: This approach relies on the controlled diffusion of iodine into water from a silicone elastomer. Silicone matrices installed in a bore well released iodine at a rate sufficient to permit the daily per capita intake of at least 100 micrograms of iodine, the amount recommended by the World Health Organization. The matrices were tested over 1 year in a village in Mali, West Africa, an area in which goiter was highly endemic. The effects on the well water and population were compared with those of a placebo system in a control village. RESULTS: An increase in urinary iodine levels was observed in the treated population, and after 12 months the incidence of goiter had fallen from 53.2% to 29.2%. CONCLUSIONS: This new concept, adaptable to all sources of water supply, may contribute to the eradication of iodine deficiency. PMID- 8460730 TI - Depressive symptoms in blood donors notified of HIV infection. AB - OBJECTIVES: Understanding more about the psychological state of persons notified of human immunodeficiency virus (HIV) infection is critical for designing notification and counseling programs that will have the most positive effect. METHODS: The subjects were blood donors who had been notified of HIV infection by the New York Blood Center. A nurse elicited a medical history, performed a limited medical examination, and asked the subjects to complete a questionnaire that included questions about drug use, sexual behavior, and psychological characteristics. The subjects completed another questionnaire approximately 2 weeks later. RESULTS: The average depressive symptom scores for both men and women were substantially higher than scores typically found in representative population samples. More than a quarter of the men and more than a third of the women reported seeking psychological or psychiatric services in the first few weeks following notification. CONCLUSIONS: Anticipating and meeting individuals' psychological needs may be necessary if HIV screening programs are to address effectively the needs of persons infected with HIV. PMID- 8460732 TI - Vitamin and mineral supplement use and mortality in a US cohort. AB - OBJECTIVES: Vitamin and mineral supplementation is a common practice in the United States, yet little is known about the long-term health effects of regular supplement use. METHODS: To examine the relationship between reported use of supplements and mortality, we analyzed data from US adults 25 to 74 years of age who were examined in the First National Health and Nutrition Examination Survey (1971 to 1975), with vital status determined through 1987. RESULTS: At baseline, 22.5% of the cohort reported using supplements regularly and 10.0% reported irregular use. The risk of mortality for regular supplement users was similar to that for nonusers. No consistent mortality benefits or risks of supplement use were found across a number of population subgroups. The risk for those who reported supplement use at both the baseline and a follow-up interview approximately 10 years later was similar to the risk for those who reported not using supplements at either interview. CONCLUSIONS: We found no evidence of increased longevity among vitamin and mineral supplement users in the United States. Considering the wide use of supplements in the general population, the cost-effectiveness and the safety of supplement use need to be better defined. PMID- 8460733 TI - Chlamydial cervical infection in jailed women. AB - OBJECTIVES: The prevalence of Chlamydia trachomatis cervical infection in incarcerated adult women has not been reported. To develop a policy for testing and treatment, we determined the prevalence of and risk factors for chlamydial infection in women in a New York City jail. METHODS: Interviews and cervical cultures for C trachomatis were obtained from 101 consenting female inmates. RESULTS: Positive cultures for C trachomatis were found in 27% of the participants. Mucopurulent cervical discharge and education of 8 years or less were two independent risk factors for infection, but only 63% of the infected women had one or both of these factors. If pelvic tenderness were considered as a third factor, an additional 7% of the infected women would have been identified. CONCLUSIONS: The prevalence of chlamydial infection in this population was as high as that in populations for which presumptive treatment is recommended. Although the optimal policy for detection and treatment of chlamydial infection may vary depending on practical considerations, we suggest that women entering correctional facilities should be screened or offered presumptive therapy for C trachomatis infection. PMID- 8460734 TI - Using a passive alcohol sensor to detect legally intoxicated drivers. AB - OBJECTIVES: We examined whether a passive alcohol sensor could be used for mass screening of motorists to accurately and quickly detect drivers whose blood alcohol concentration exceeded a variety of levels often established as per se evidence of legal intoxication. METHODS: In a voluntary roadside survey, 1181 late-night drivers in Minnesota were interviewed. Breath measurements were taken with both a passive alcohol sensor and an evidentiary quality portable breath test device. RESULTS: Measurements could be taken much more easily and quickly with the passive sensor, whose readings correlated very strongly (r = .87) with the evidentiary device. Moreover, for criterion blood alcohol concentration levels ranging from 100 mg/dL to 20 mg/dL, a large proportion of motorists could be accurately identified as being above or below the criterion, with relatively few false-negative or false-positive identifications. CONCLUSIONS: The use of passive alcohol sensors at sobriety checkpoints should allow motorists to be processed very quickly with minimal inconvenience. At the same time, detection of legally intoxicated motorists will probably be substantially increased and the general deterrent value of per se alcohol-impaired driving laws enhanced. PMID- 8460735 TI - Activating communities for health promotion: a process evaluation method. AB - OBJECTIVES: To date, evaluations of community-based prevention programs have focused on assessing outcomes, not the process of organizing communities for health promotion. An approach was developed to analyze community organization efforts aimed at advancing community health objectives. These organizational processes are referred to as community activation. METHODS: Information was gathered from 762 informants through a key informant survey conducted in 28 western communities. The data collected included informant ratings of community activation and information about interorganizational activities analyzed through network analytic techniques. RESULTS: Activation levels, as measured by informant ratings, varied across communities. Program coordination, as measured by network analysis, occurred, on average, approximately 30% of the time. Higher income communities tended to be more activated than lower income communities. CONCLUSIONS: There is a widely recognized need for improved information about health-related community organization activities. It appears possible to gather such information through key informant surveys and to develop measures of community organization status that can be used in the evaluation of community health promotion programs. PMID- 8460736 TI - Prevalence of HIV infection among psychiatric patients in a New York City men's shelter. AB - We report on the prevalence of human immunodeficiency virus (HIV) infection among psychiatric patients in a New York City shelter for homeless men. We reviewed the records of all 90 men discharged from the shelter psychiatry program to community housing over a 2-year period. HIV serostatus was recorded for 62 of the 90 men. Of these 62, 12 (19.4%) were positive. There were 28 men whose serostatus was not recorded. Data on the HIV risk behaviors of these 28 men suggested that seroprevalence could have been similarly high among them. The results indicate an urgent need to develop and apply preventive interventions for HIV in this population. PMID- 8460737 TI - Increasing frequency of heterosexually transmitted AIDS in southern Florida: artifact or reality? AB - Acquired immunodeficiency syndrome (AIDS) cases reported as the result of heterosexual contact have been increasing in the United States, with Florida reporting a disproportionate number. We investigated 168 such AIDS cases from southern Florida. After follow-up, 50 (30%) patients were reclassified into other transmission categories. The data suggest that the increased rate of heterosexually acquired AIDS cases reported from southern Florida was partially related to misclassification of risk. PMID- 8460738 TI - Public reactions to AIDS in the United States: a second decade of stigma. AB - The pervasiveness of stigma in the United States related to the acquired immunodeficiency syndrome (AIDS) was assessed in telephone interviews with a general adult sample (n = 538) and an African-American sample (n = 607). Most respondents manifested at least some stigma. African Americans expressed greater support for policies separating persons with AIDS from others and a stronger desire to avoid these persons, whereas Whites expressed more negative feelings toward them and a greater willingness to blame them for their illness. Regardless of race, men were more likely than women to support policies such as quarantine and to say that they would avoid persons with AIDS. PMID- 8460739 TI - Changes in HIV rates and sexual behavior among homosexual men, 1984 to 1988/92. AB - Data were collected from 1614 homosexual and bisexual men in 1984 through 1985 and from 1988 to 1992 in Pittsburgh. Of the men entering the study since 1988, 16% reported engaging in unprotected anal receptive intercourse with more than one partner during the 6 months before their visit. Approximately 7% of the younger men and 18% of the men over 22 years of age in the recent cohort were already infected with the human immunodeficiency virus, the same rates as those described 8 years ago. Aggressive risk-reduction programs are needed in high schools and existing networks in the gay community. PMID- 8460740 TI - Reported asthma among Puerto Rican, Mexican-American, and Cuban children, 1982 through 1984. AB - Data from the Hispanic Health and Nutrition Examination Survey (HHANES) (1982 through 1984) and the National Health and Nutrition Examination Survey (NHANES) II (1976 through 1980) were used to examine reported physician-diagnosed asthma among 6-month-old through 11-year-old children. The highest prevalence of active asthma was reported for Puerto Ricans: 11.2% compared with 3.3% for non-Hispanic Whites, 5.9% for non-Hispanic Blacks, 2.7% for Mexican Americans, and 5.2% for Cubans. Health services utilization and severity do not appear to explain the differences between Puerto Ricans and Mexican Americans. Educational programs on asthma should consider focusing on Puerto Ricans. PMID- 8460741 TI - Complications of BCG vaccinations in rural Haiti. AB - This study investigated an outbreak of axillary lymphadenitis and abscesses after Bacillus Calmette-Guerin vaccination among rural Haitian children treated at the Hospital Albert Schweitzer from January 1986 through March 1991. Seventy-seven cases of vaccine-related complications were identified, all among children immunized before the age of 1 year. The proportions of children with complications were 0.017% for 1986 through 1989, 0.91% for 1990, and 2.2% for January through March 1991. PMID- 8460742 TI - The alcohol warning label and adolescents: the first year. AB - Awareness of the alcohol labeling law and exposure to, beliefs about, and memory for the government-mandated alcohol warning label were measured in a sample of adolescents immediately before the label was required to appear (in the fall of 1989) and 1 year after the label was required. After the label was required, there were increases in awareness, exposure, and recognition memory, but there were not substantial changes in alcohol use or beliefs about the risks written on the warning. PMID- 8460743 TI - Diagnostic x-ray exposure and lens opacities: the Beaver Dam Eye Study. AB - The Beaver Dam Eye Study is a population-based study of common age-related eye diseases. During the standardized medical history, the 4926 subjects were asked whether they had ever had a chest x-ray, computerized axial tomography (CAT) scan of the head, other x-rays of the head, x-rays of the abdomen, or other diagnostic x-rays. The eye examination included photographs of the lenses of the eyes, which were subsequently graded according to protocol. Nuclear sclerosis and posterior subcapsular opacity were significantly associated with CAT scans. If these relationships are causal, it would highlight the importance of minimizing such exposure to the lens of the eye. PMID- 8460744 TI - Cardiovascular disease risk factors: improvements in knowledge and behavior in the 1980s. AB - This study surveyed 4158 adults residing in two control cities of the Stanford Five-City Project. Analysis of five cross-sectional surveys (conducted in 1979 through 1990) demonstrated improvements in respondents' general cardiovascular disease risk factor knowledge and behaviors. Cholesterol-related knowledge and behavior showed particularly marked improvements. PMID- 8460745 TI - Groundwater surveying and management: an interagency effort in Michigan. PMID- 8460746 TI - Management issues in a major typhoid fever outbreak. PMID- 8460747 TI - HIV surveillance testing: taking advantage of the disadvantaged. PMID- 8460748 TI - Colorado's HIV partner notification program. PMID- 8460749 TI - Non-Hodgkin's lymphoma and occupational exposure to hair dyes among people with AIDS. PMID- 8460750 TI - Study of hypertension in urban bus drivers questioned. 1. Hypoglycemic agents, intrinsic stress may be factors. PMID- 8460751 TI - Study of hypertension in urban bus drivers questioned. Study design as source of bias. PMID- 8460752 TI - Percutaneous dilational tracheostomy. Completing the anaesthetist's range of airway techniques. PMID- 8460753 TI - Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia. AB - The neuromuscular effects of intravenous rocuronium bromide, 0.6 mg.kg-1 or 0.9 mg.kg-1, were studied in four groups of 10 patients during anaesthesia with or without halothane (0.5-0.75% inspired concentration). Neuromuscular block was monitored using mechanomyography and train-of-four stimulation. The mean times to onset of complete neuromuscular block were 58 and 59 s using the 0.6 mg.kg-1 dose in patients anaesthetised with fentanyl and halothane respectively. The times of 34 min and 33 min for 25% recovery of T1 (first response in the train of four), 54 min and 52 min for 90% recovery of T1, 55 min and 60 min for a train of four ratio of 0.7, and 13 and 13 min respectively for the recovery index (25-75% recovery of T1) were not significantly different in these groups. Complete block with the 0.9 mg.kg-1 dose occurred in 47 s and 44 s respectively in the fentanyl and halothane groups. T1 recovered to 25% in 51 min and 58 min, and to 90% in 77 min and 86 min respectively in the two groups. The recovery indices and the times to spontaneous recovery of the train of four ratio to 0.7 were 17 min and 19 min, and 83 min and 93 min respectively. All the parameters were significantly different between the 0.6 mg.kg-1 and 0.9 mg.kg-1 doses. Halothane in the concentrations used did not influence the neuromuscular effects. It is concluded that rocuronium is a rapidly acting non-depolarising muscle relaxant with a duration of action similar to that of vecuronium and may be a useful alternative to suxamethonium for rapid tracheal intubation. PMID- 8460754 TI - A review of 2000 consecutive ICU admissions. AB - The working practices and outcomes from UK intensive care units are poorly documented to date. We have reviewed 2000 consecutive admissions to one intensive care unit in a tertiary referral centre with initially six, then eight beds. The study was a retrospective review of contemporaneous data collection within the period 1986-1990. Demographic details, referral source, admission time, admission diagnosis, APACHE II score, therapeutic interventions, and outcome were recorded. A high overall mortality in the intensive care unit (23%), proportional to APACHE II scoring on admission, was demonstrated. This reflects the referral of many patients who have, or who develop, multiple organ failure. Mortality was significantly higher in patients over the age of 40 years. A total of 69.5% of patients were admitted outside the hours 0800-1800 h on Monday to Friday and admissions peaked between 1200 and 2100 h, demonstrating the need for senior out of-hours cover. These figures may be used to compare future mortality and work practices in this and other units. The report illustrates some of the advantages and disadvantages of one method of data collection. As it represents one unit only, care must be taken in extrapolating results to others. The timing of admissions suggests that a review of medical staffing practices would be useful. PMID- 8460755 TI - Propofol and fentanyl act additively for induction of anaesthesia. AB - The induction dose-response of propofol was compared with the dose-response of its combination with fentanyl and with that of fentanyl alone in three groups of 60 women undergoing minor gynaecological surgery. Dose-response curves were determined for each group using bootstrap and isobolographic analyses. Propofol was found to act additively with fentanyl for induction of anaesthesia. Twenty three percent of the ED50 of fentanyl was required in combination with 75% of the ED50 for propofol to achieve the ED50 of the combination. This indicates that, for induction of anaesthesia, propofol and fentanyl are not synergistic. PMID- 8460756 TI - Effects of omeprazole, with and without metoclopramide, in elective obstetric anaesthesia. AB - We report the results of a study comparing two dose regimens of the gastric antisecretory agent, omeprazole, used as prophylaxis against pulmonary aspiration of gastric contents during general anaesthesia for elective Caesarean section. Since antisecretory agents do not clear stomach contents already present at the start of treatment, two groups of patients who had received both omeprazole and a prokinetic drug, metoclopramide, were also studied. Thirty patients received oral omeprazole 40 mg on the evening before and on the morning of the operation (group 1), 33 received oral omeprazole 80 mg on the morning of the operation (group 2), and 15 (group 3) and 16 (group 4) patients respectively received the oral omeprazole doses stated above and in addition metoclopramide 10 mg given intramuscularly at least 20 min before induction of anaesthesia. Gastric aspirate pH and volume were measured at induction of anaesthesia and on completion of surgery. At induction of anaesthesia, treatment was judged successful (pH > or = 2.5 and volume < 25 ml) in 87%, 73%, 100% and 81% of patients in groups 1-4 respectively. The corresponding results on completion of surgery were 100%, 88%, 100% and 100%. While omeprazole is useful as prophylaxis against pulmonary aspiration during general anaesthesia for elective Caesarean section, the addition of a prokinetic agent seems to be necessary to maximise its effects. PMID- 8460757 TI - Can pre-emptive lumbar epidural blockade reduce postoperative pain following lower abdominal surgery? AB - In a double-blind study, 36 patients who received a standard general anaesthetic for abdominal hysterectomy or myomectomy, received either 15 ml of bupivacaine 0.5% with adrenaline by lumbar epidural injection 15 min before surgery (group A) or the same dose at the end of surgery but before waking (group B). Pain was assessed for 24 h by cumulative morphine dose (self-administered by patient controlled analgesia), visual analogue scale and verbal rating score. Patients were included for analysis if they were pain free on waking and for at least 2 h after. There was no significant difference (p > 0.05) between the two groups in morphine dose, visual analogue scale or verbal rating score at 6 and 24 h after waking. As expected, there was a significant difference in the mean time of first use of patient-controlled analgesia (4.26 h in group A vs 5.06 h in group B, p < 0.05). Consequently, we compared the morphine dose, visual analogue scale and verbal rating score at 23 h in group A with those at 24 h in group B. Again there were no significant differences between the two groups. We were unable to demonstrate that epidural blockade had a significantly better effect on postoperative pain when administered before, rather than after, surgery. PMID- 8460758 TI - Combined infusions of morphine and ketamine for postoperative pain in elderly patients. AB - The value of using a combined infusion of morphine with a variable dose of ketamine for postoperative analgesia following upper abdominal surgery was assessed in a double-blind randomised study of 40 elderly patients. Four groups of 10 patients received an infusion of morphine at 1 mg.h-1, either alone, or combined with ketamine at a rate of 5, 10 or 20 mg.h-1. The addition of ketamine to a continuous infusion of morphine did not significantly improve either analgesia or postoperative lung function. Increasing the dose of ketamine resulted in an increased incidence of postoperative dreaming (p < 0.01). PMID- 8460759 TI - Epidural anaesthesia through caudal catheters for inguinal herniotomies in awake ex-premature babies. AB - Ex-premature babies are at risk of apnoea after surgery. Regional anaesthesia has been used as an alternative to general anaesthesia for some surgical procedures in the belief that it may be safer. However, single dose caudal epidural and subarachnoid anaesthetics have a duration of action which may be insufficient for some operations. The level and duration of anaesthesia can be extended if local anaesthetic is given through an epidural catheter. In addition, the dose needed to provide adequate anaesthesia may be lower because the local anaesthetic is given at an appropriate segmental level. We report our experience of caudal epidural anaesthesia in nine, awake ex-premature babies who were having inguinal herniotomies. The anaesthesia was excellent in six babies. Two babies cried briefly with peritoneal or spermatic cord traction. One other baby needed supplementation with nitrous oxide in oxygen in order to complete the surgery. The majority of babies slept throughout surgery. There were no reported postoperative complications. PMID- 8460760 TI - Blood loss following tonsillectomy in children. A blind comparison of diclofenac and papaveretum. AB - One hundred and ninety-eight children, aged 3 to 12 years, who were scheduled for tonsillectomy were randomly allocated to receive either diclofenac 1.0 mg.kg-1 or papaveretum 0.2 mg.kg-1 by intramuscular injection after induction of anaesthesia. There were no significant differences between the treatment groups in operating theatre blood loss, the frequency of bleeding on the ward, or the need for operative haemostasis. However, the incidence of above average bleeding in the recovery room was significantly higher in the diclofenac group (p < 0.05). Similarly, marked restlessness in the recovery room was more frequent in the diclofenac group (p < 0.01). In both treatment groups there was an association between bleeding and restlessness during recovery so the increased bleeding in the diclofenac group may not be a direct effect. PMID- 8460761 TI - Subcutaneous emphysema in labour. AB - Spontaneous subcutaneous and mediastinal emphysema is a rare but potentially dangerous complication of labour. The condition was observed in an 18-year-old primigravida in the first stage of labour, who subsequently required Caesarean section which was performed under epidural anaesthesia. PMID- 8460762 TI - A case of acute poisoning due to organophosphate insecticide. AB - A case of acute severe organophosphate poisoning by deliberate self administration is reported. The patient required intensive therapy for 30 days. Unusual features of the case were the avoidance of atropine, because of the high risk of ventricular fibrillation, and the ineffectiveness of pralidoxime. PMID- 8460763 TI - Skin necrosis following continuous positive airway pressure with a face mask. AB - A 60-year-old woman with respiratory failure required ventilatory support using a continuous positive airway pressure face mask. She developed extensive necrosis of the skin of the bridge of the nose. A number of precipitating factors are discussed and suggestions made to minimise the risk of this complication. PMID- 8460764 TI - Association of anaesthetist's checklist for anaesthetic machines. Problem with detection of significant leaks. AB - Eight experienced anaesthetists performed a 'cockpit drill', following instructions in the Association of Anaesthetist's checklist, on an anaesthetic machine that had a significant leak (3 l.min-1 at a pressure of 16 kPa). Only one anaesthetist detected the leak and this was by audible means rather than by any of the protocol's set manoeuvres. We demonstrated that a leak of 3 l.min-1 from the flowmeter block resulted in an inspired oxygen concentration of 6% when the anaesthetic machine was used with a minute volume divider ventilator. PMID- 8460765 TI - Pleural drainage systems. AB - The physics and the physiological principles of pleural or chest drainage systems are reviewed. The clinical management and complications of pleural drainage are summarised. PMID- 8460766 TI - Coeliac plexus block with bupivacaine reduces intestinal dysfunction in neurosurgical ICU patients. AB - Coeliac plexus block, an established method of treatment for pain associated with pancreatitis and cancer, was used in neurosurgical patients with gastrointestinal dysfunction. The study was performed in 16 patients whose gastric reflux volume exceeded 600 ml per day for 3 consecutive days. Patients were allocated to a block group (n = 8) or a control group (n = 8). Coeliac plexus block was accomplished with a modified Moore technique using 50 ml bupivacaine 0.25%. In the block group, gastric reflux volumes for 3 days preceding coeliac plexus block and 3 consecutive days following coeliac plexus block were analysed. In the control group, gastric reflux volumes were observed over a period of 6 days. Mean (SEM) gastric reflux volume decreased significantly following coeliac plexus block from 770 (50) ml to 60 (30) ml (p < 0.01). In the control group, gastric reflux remained unchanged over the corresponding periods (730 (60) ml c.f. 670 (50) ml). The response of gastric reflux volume to coeliac plexus block suggests that the mechanism is related to inhibition of sympathetic activity in patients whose sympathetic drive is increased due to the underlying neurological disease, and possibly due to sedation withdrawal symptoms. PMID- 8460768 TI - Functionally crossed pipelines. PMID- 8460767 TI - Audit of pre-operative starvation. AB - An audit of pre-operative starvation at Huddersfield Royal Infirmary has been undertaken. It shows that both adults and children are starved for significantly longer than the hospital's official starvation policy requires. The mean starvation time for children was almost 10 h, which is longer than the 8 h required before hypoglycaemia becomes a risk. A review of the literature suggests that only 3 h of fluid withdrawal is necessary. Possible ways to improve pre operative starvation regimens are discussed. PMID- 8460769 TI - Hoarseness after tracheal intubation. PMID- 8460770 TI - Delayed profound respiratory depression after premedication with trimeprazine. PMID- 8460772 TI - Reservoir requirements of the PAC portable anaesthesia system. PMID- 8460771 TI - Delayed profound respiratory depression after premedication with trimeprazine. PMID- 8460773 TI - Combined spinal/epidural anaesthesia for caesarean section. PMID- 8460774 TI - Eldor combined spinal/epidural needle. PMID- 8460775 TI - Foreign bodies in the larynx. PMID- 8460776 TI - A simple and cheap aid to blind nasal intubation. PMID- 8460777 TI - An introducer for the flexible laryngeal mask airway. PMID- 8460778 TI - Not another high block. PMID- 8460779 TI - When to remove the laryngeal mask airway. PMID- 8460780 TI - Misuse of a Bodok seal. PMID- 8460781 TI - Transdermal hyoscine--timing of patch. PMID- 8460782 TI - Phaeochromocytoma without raised pre-operative catecholamine levels. PMID- 8460783 TI - Delayed diagnosis of contralateral tension pneumothorax during thoracotomy--an example of fixation error. PMID- 8460784 TI - Broken needle complicating arterial cannulation. PMID- 8460785 TI - Nil by mouth after midnight. PMID- 8460786 TI - The pre-operative anaesthetic visit. PMID- 8460787 TI - Problems with a new spray. PMID- 8460788 TI - The importance of checking ampoule labels. PMID- 8460789 TI - Tracheal intubation of children in intensive care. PMID- 8460790 TI - Learning fibreoptic intubation: fundamental problems. PMID- 8460791 TI - Learning fibreoptic intubation: fundamental problems. PMID- 8460792 TI - Checking anaesthetic machines--checklists or visual aids? PMID- 8460793 TI - Pharmacokinetic model-controlled infusion of midazolam. A prospective evaluation during general anaesthesia. AB - The accuracy of a computer-controlled infusion of midazolam, based on previously published pharmacokinetic parameters, was tested prospectively in 12 adult female patients undergoing general anaesthesia. Anaesthesia consisted of an initial bolus followed by an exponentially decreasing infusion of midazolam given according to body weight, fentanyl, nitrous oxide and vecuronium. Venous blood samples were taken at 15 min-intervals throughout the procedures and for 1-2 h postoperatively. The bias of the model was -5.1% (95% CI -11.3 to 1.2%) and precision 24.8% (95% CI 20.9 to 28.6%). Least squares regression analysis decreased the bias to -2.8% but did not alter precision. Retrospective fitting of an alternative set of published parameters for midazolam resulted in significant deterioration of the model. The precision was similar to that found in past studies of intravenous anaesthetic agents. Further improvement in the accuracy of midazolam infusion awaits improved understanding of the causes of pharmacokinetic variability. PMID- 8460794 TI - Brainstem auditory evoked response during propofol anaesthesia in children. AB - The effect of propofol on the brainstem auditory response was studied in 10 healthy children presenting for elective general surgery. A computer-controlled infusion of propofol was used to induce and maintain anaesthesia. Basal brainstem auditory evoked responses were recorded in the awake child and at different infusion rates of propofol. Significant increases in the latencies of the brainstem waves III and V and the interpeak intervals I-V and III-V were seen and were dose dependent. The changes were small and would not preclude the use of propofol anaesthesia for brainstem auditory evoked response testing in children. PMID- 8460795 TI - Closed loop control of arterial hypertension following intracranial surgery using sodium nitroprusside. A comparison of intra-operative halothane or isoflurane. AB - Forty patients were chosen at random to receive halothane or isoflurane anaesthesia during craniotomy and a comparison of the postoperative hypertensive response was made using a microcomputer-based closed-loop arterial pressure control system with sodium nitroprusside to control and assess arterial pressure during the first 6 postoperative hours. A desired target systolic pressure was chosen for each patient and the frequency of hypertension, sodium nitroprusside requirements and quality of arterial pressure control were compared between the two groups. Thirty-five patients required sodium nitroprusside. The halothane group required a median dose of 15.2 mg (range 0-72) compared to 3.4 mg (range 0 87) in the isoflurane group. This difference is not statistically significant. Quality of arterial pressure control was satisfactory in both groups. In conclusion, arterial hypertension occurs frequently following intracranial surgery and is uninfluenced by the choice of halothane or isoflurane intra operatively. This closed-loop arterial pressure control system functioned safely and effectively in this context. PMID- 8460796 TI - Effect of extradural anaesthesia on the ventilatory response to hypoxaemia. AB - The effect of lumbar or thoracic extradural anaesthesia on the ventilatory response to progressive isocapnic hypoxaemia was studied in two groups of 10 unpremedicated patients. The ventilatory measurements were taken twice, before and 20 min after the administration of 10 ml of lignocaine 2%. Lumbar extradural anaesthesia did not change the slope of the hypoxic response curve, but it significantly increased minute ventilation by 27% at an arterial oxygen saturation of 90%. Thoracic extradural anaesthesia was not associated with any changes in either index. We conclude that neither lumbar nor thoracic extradural anaesthesia impairs the ventilatory response to progressive isocapnic hypoxaemia. PMID- 8460797 TI - Sedation with propofol during surgery under local blockade. Assessment of a target-controlled infusion system. AB - The ability of a target-controlled propofol infusion system to provide sedation for 40 patients undergoing surgery under regional blockade was assessed. Eighty eight per cent of the total infusion time was at the desired sedation level with little oversedation. This was achieved with a median blood propofol concentration of 0.93 micrograms.ml-1. The pharmacokinetic algorithm performed as well when used for sedation as for total intravenous anaesthesia. The predicted and measured blood propofol concentrations showed a bias of -12% and a precision of 34%. PMID- 8460798 TI - The effect of oral ondansetron in the prevention of postoperative nausea and vomiting after major gynaecological surgery performed under general anaesthesia. AB - The efficacy and safety of ondansetron in preventing postoperative nausea and vomiting following major gynaecological surgery was evaluated in this multicentre, double-blind study. A total of 243 patients were randomised to receive three doses of oral ondansetron 8 mg or matching placebo at 8-hourly intervals, with the first dose being given an hour before surgery. A standard general anaesthetic technique was employed throughout. Nausea, vomiting and safety assessments were performed continuously during the 24 h postrecovery period. Of the 237 patients evaluated for efficacy, significantly fewer ondansetron 8 mg treated patients (65/117; 56%) experienced postoperative nausea and/or vomiting compared with placebo-treated patients (94/120; 78%) during the study period (p < 0.001). In addition, ondansetron 8 mg reduced the severity of nausea (p < 0.001) and the total number of vomiting episodes experienced (p < 0.001). Overall, ondansetron 8 mg was well tolerated and effective in preventing postoperative nausea and vomiting in this surgical setting. PMID- 8460800 TI - The management of tracheal rupture using bilateral bronchial intubation. AB - The management of a patient who required positive pressure ventilation following pharyngolaryngo-oesophagectomy during which tracheal injury was sustained is described. Ventilation with a tracheal tube resulted in a massive pneumoperitoneum. Bilateral bronchial intubation was employed with success. PMID- 8460799 TI - The effect of the anaesthetist's attire on patient attitudes. The influence of dress on patient perception of the anaesthetist's prestige. AB - Two groups of adult patients (55 each) were visited pre-operatively by an anaesthetist who was dressed either formally or casually. Their response to this visit, their opinions regarding anaesthetists and their knowledge of anaesthetic work were elicited afterwards by means of a questionnaire. Patients' satisfaction with the anaesthetist and his/her visit was not influenced by dress. The anaesthetist was awarded a high level of prestige and the length of his/her training was recognised to be comparable to that of other professionals; 81.8% of patients thought that anaesthetists held a medical degree but only 35.4% thought that they worked in the intensive care unit. Patients expressed a preference for doctors to wear name tags, white coats and short hair but disapproved of clogs, jeans, trainers and earrings. PMID- 8460801 TI - Continuous spinal anaesthesia in acute respiratory failure. AB - A patient with an obstructed femoral hernia and intercurrent respiratory failure was successfully anaesthetised with a continuous spinal technique. The technique provided excellent intra-operative anaesthesia and early postoperative analgesia, whilst avoiding further respiratory compromise. Disconnection of the catheter hub from the catheter prevented prolonged provision of postoperative analgesia by this route. Fixing of both the catheter and the hub to the patient are advocated to avoid this problem. PMID- 8460802 TI - A very small dose of suxamethonium relieves laryngospasm. AB - Intravenous suxamethonium, in a dose as small as 0.1 mg.kg-1, has been found to be reliable in the treatment of laryngeal spasm. Three episodes of vocal cord spasm observed during direct laryngoscopy were relieved by this dose of suxamethonium. PMID- 8460803 TI - A comparison of the laryngeal mask airway and Guedel airway, bag and facemask for manual ventilation following formal training. AB - Ten volunteers, with no previous experience of resuscitation, were formally trained in the use of the laryngeal mask airway and the oropharyngeal airway (Guedel), bag and facemask for manual ventilation of the lungs in 104 fit, anaesthetised adults. They then used both airways in turn. The order of insertion was randomly allocated, and the times taken for insertion were also recorded. Ventilation for each airway was deemed to be successful if an increase in end tidal carbon dioxide partial pressure did not occur and arterial oxygen saturation remained greater than 90%. Success rates for the laryngeal mask airway and the Guedel airway, bag and facemask were 87% and 43% respectively (p < 0.001) and the average insertion times were 27.4 s (SEM 1.5) and 15.8 s (SEM 0.50) (no significant difference), respectively. The laryngeal mask airway proved to be easier to use for manual ventilation than the Guedel airway, bag and mask for inexperienced personnel who had received a period of formal training in both techniques. PMID- 8460804 TI - The minilink breathing system: resistance and suitability for spontaneous ventilation. AB - The Portex infant breathing/ventilation systems with 8.5 mm and 15 mm internal diameter connectors were compared with a standard T-piece which had a 15 mm connector and 22 mm internal diameter tubing. The differential pressures across each system were measured at constant fresh gas flows up to 30 l.min-1 dry air. Resistance was calculated at flows compatible with quiet respiration and peak inspiratory flow. Flow resistance of the 3.0 mm internal diameter tracheal tube in conjunction with the minilink breathing systems were similar to those previously reported for tracheal tubes alone. However, the minilink breathing system assumed a greater influence on resistance when tracheal tubes of larger internal diameter were used. It added considerably more resistance than the standard tubing. This may have a deleterious effect during spontaneous ventilation in older children. PMID- 8460805 TI - The rebreathing characteristics of the Hudson oxygen mask. AB - A lung model was used to study the effect of varying minute ventilation, oxygen flow and inspiratory : expiratory ratio on the rebreathing characteristics of the Hudson oxygen mask. The onset of rebreathing was detected using two different sets of criteria; those defined by Kain et al. and Humphrey. The onset of rebreathing was also quantified in terms of the inspired volume of carbon dioxide and increases in deadspace. The magnitude of rebreathing was increased by reducing oxygen inflow and increasing minute ventilation. Variation in I : E ratio between 1 : 1 and 1 : 4 had little effect on rebreathing. Using the clinical criteria of Kain et al, the onset of rebreathing was detected when oxygen inflow/minute ventilation ratio was reduced below 0.78 on average. With the other criterion, rebreathing occurred when the ratio was 0.46. PMID- 8460806 TI - Laboratory assessment of the Baxter disposable patient-controlled analgesia system. AB - The performance of the Baxter patient-controlled analgesia infusor system was assessed in the laboratory. The flow of the 5 ml.h-1 infusor was measured gravimetrically with the flow restrictor maintained at 31 degrees C and the reservoir at either 20 degrees C or 25 degrees C. At 25 degrees C the mean flow was 4.98 (SEM 0.06) ml.h-1 and at 20 degrees C the mean flow was 4.32 (0.05) ml.h 1. The patient-control module performed reliably, delivering a mean of 0.42 (0.001) ml following depression of the button, slightly less than the manufacturer's quoted value of 0.5 ml. PMID- 8460807 TI - Dural taps revisited. A 20-year survey from Birmingham Maternity Hospital. AB - The records from 34,819 obstetric epidurals performed at Birmingham Maternity Hospital over the period 1969-1988 were examined. During that time there were 460 dural taps (overall incidence 1.3%). Of the methods used to detect the epidural space, loss of resistance to injection of saline was associated with the lowest incidence of dural tap (0.6%). The incidence of typical postdural puncture headache when managed conservatively was 86%. Provision of an epidural drip after delivery reduced the incidence of headache to 70%. Elective forceps delivery conferred no additional benefit, and tended to delay the onset of headache. Blood patches were performed on 135 patients and provided complete relief of headache in 93 (68%). A further 23 patients (16%) obtained partial relief. PMID- 8460808 TI - Patient-controlled analgesia with and without background infusion. Analgesia assessed using the demand: delivery ratio. AB - Sixty adult patients following general surgical operation were treated with patient-controlled analgesia using morphine. Patients were allocated into three groups to receive: no background infusion, a 1 mg.h-1 or a 2 mg.h-1 background infusion. The other controls on the patient-controlled analgesia machine were set to allow a maximum dose of morphine of 6 mg.h-1 to each group. Analgesia was assessed after 4 and 24 h using a 100 mm horizontal visual analogue scale. The number of analgesic requests made by the patient and the number of those requests which resulted in successful deliveries was recorded. Patients who received a regimen including a background infusion had improved pain relief, particularly in the first 4 h of treatment (p < 0.05). Patients who received a background infusion of 2 mg.h-1 had an increased incidence of nausea (p < 0.05). A background infusion of 1 mg.h-1, with a 1 mg bolus dose and a 12 min lockout interval provided acceptable pain relief without excessive nausea. In all three groups the ratio of analgesic requests to successful deliveries correlated with the degree of pain reported by visual analogue score (p = 0.0001). PMID- 8460809 TI - A comparison of propofol and methohexitone for dental chair anaesthesia in children. AB - Fifty healthy children presenting for outpatient exodontia received either propofol or methohexitone for induction. Anaesthesia was maintained in both groups using 50% oxygen in nitrous oxide and 1-2% halothane. Those receiving methohexitone maintained a significantly higher mean arterial pressure and heart rate than the propofol group. Nine percent of patients in the propofol group developed ventricular arrhythmias, compared to 32% in the methohexitone group. PMID- 8460810 TI - Anaesthesia for procedures on the larynx and pharynx. The use of the Bullard laryngoscope in conjunction with high frequency jet ventilation. AB - Twenty patients undergoing elective procedures on the larynx and pharynx were anaesthetised using a propofol infusion and a bolus of vecuronium. High frequency jet ventilation was employed via a 7 French gauge catheter, with a second catheter being used to measure expired carbon dioxide levels. The Bullard laryngoscope was compared with the Macintosh instrument both for visualising the larynx and subsequently inserting a catheter. One catheter was left in place until the patient was fully awake, and in one case this enabled gas exchange to be maintained in the presence of laryngospasm. Using the Bullard laryngoscope, intubation was possible in all 20 patients, in a mean time of 22 (6.8) s. Using the Macintosh laryngoscope only 16 patients could be intubated and this took significantly longer at 34 (18.3) s (p < 0.05). The Bullard laryngoscope and high frequency jet ventilation offer a reliable method of intubating and anaesthetising patients with upper airways pathology and further benefits may accrue in the recovery period. PMID- 8460811 TI - Anaesthetic machine checking practices. PMID- 8460812 TI - Inhalational agents and the Servo ventilator. PMID- 8460813 TI - Anaesthesia and upper respiratory tract infections. PMID- 8460814 TI - Whatever happened to the premedication? PMID- 8460815 TI - The influence of methane on the infrared measurement of anaesthetic vapour concentration. PMID- 8460816 TI - A perforated diaphragm--enough to raise anyone's blood pressure! PMID- 8460817 TI - Unexpectedly high spinal anaesthesia following failed extradural anaesthesia for caesarean section. PMID- 8460818 TI - Pathogenesis of post-immersion collapse. PMID- 8460819 TI - 'Vocalaid' and surgical emphysema. PMID- 8460820 TI - Cocaine dosage in rhinosurgery. PMID- 8460821 TI - Bite guard for laryngeal mask airway. PMID- 8460822 TI - Catecholamine response to laryngoscopy and intubation after thiamylal or ketamine induction of anaesthesia. PMID- 8460824 TI - The oesophageal detector device in the asthmatic patient. PMID- 8460823 TI - Information processing under anaesthesia. PMID- 8460825 TI - Support for the Waters' canister. PMID- 8460826 TI - Intrathecal pethidine: a word of caution. PMID- 8460827 TI - A brief history of nuclear magnetic resonance. PMID- 8460828 TI - Design of a glucose minisensor based on streptavidin-glucose oxidase complex coupling with self-assembled biotinylated phospholipid membrane on solid support. AB - A simple and fast procedure to prepare a glucose-sensitive minielectrode is presented. It is based on a biotin-modified phospholipid bilayer to which a streptavidin-glucose oxidase complex is coupled. The assay is based on the electrochemical detection of enzymatically generated hydrogen peroxide at the potential +670 mV. In the case of an air-saturated buffering solution the response to glucose was measured up to 50 mmol.L-1, with a linear portion up to 7 mmol.L-1. The influence of oxygen tension, pH, and temperature as well as possibly interfering substances was investigated. The prospect usage for the measurement of blood and urine was tested. PMID- 8460829 TI - Detection and evaluation of fragrances by human reactions using a chemical sensor based on adsorbate detection. AB - Human reactions and sensor responses to 37 typical fragrances are investigated in order to develop a chemical sensor which can detect fragrances and evaluate them in subjective terms of human reactions. Eight female test subjects recorded their reactions to these fragrances by grading them on a seven-point scale in terms of 55 descriptive characteristics. Their reactions fell into two general categories, "pleasantness" and "freshness (elegance)", dependent on the characteristic chemical structure of the fragrances. The women evaluate the fragrances mainly by the degree of pleasantness and freshness (elegance). A set of eight plezoelectric sensors incorporating different hydrophobic polymer materials is fabricated to predict such human reactions because their adsorbate detection and pattern recognition are similar to those in humans. The sensors were effective in detecting hydrophobic fragrances in the gas phase, and their fragrance classifications were similar to human ones. The sensor responses to the adsorbate correlate significantly with two of the human responses with multiple correlation coefficients of more than 0.6 (p < 0.02). Namely, the sensor can predict two different human reactions to fragrances simultaneously, suggesting the possibility of developing an artificial olfactory sensor based on adsorbate detection. PMID- 8460830 TI - Determination of total polyamines in tumor cells by high-performance capillary zone electrophoresis with indirect photometric detection. AB - Tumor cells contain much higher levels of common polyamines such as putrescine, spermidine, and spermine than normal cells. Our previous work demonstrated that high-performance capillary zone electrophoresis with indirect photometric detection was suitable for the determination of underivatized free polyamines in tumor cells. We now report improved sensitivity (7-fold), greater quantitative reproducibility, and quantitation of both bound and free, underivatized polyamines in PC 12 tumor cells. 1,7-Diaminoheptane was used as an internal standard for quantification. Femtomoles of three polyamines and simple cations such as K+ and Na+ were easily separated in less than 10 min. The quantitations for total spermidine and spermine (bound and free) were found to be 2-fold higher than the quantitation for free, unbound polyamines using our previous method. The signal response was linear over 2 orders of magnitude. The method described here provides a fast and simple technique for quantitation of bound, unbound, and total polyamines for use in the study of the biological role of polyamines. PMID- 8460831 TI - Determination of methylmercury in fish samples using GC/AA and sodium tetraethylborate derivatization. AB - A simple technique is described for the rapid determination of methylmercury in fish tissue. Following simple dissolution in methanolic KOH solution, aqueous phase ethylation by derivatization with NaB(C2H5)4, cryogenic trapping on a packed chromatographic column, and GC separation, volatile mercury species are detected by atomic absorption spectrometry. Absolute detection limits are 4 pg of Hg for CH3Hg+ and 75 pg of Hg for labile Hg2+. Concentration detection limits for this optimized procedure are 4 ng of Hg for CH3Hg+ and 75 ng of Hg for labile Hg2+ per gram of pulverized dried fish tissue. Analysis of standard reference materials demonstrates the accuracy, precision, and reproducibility of the analytical method. PMID- 8460832 TI - Investigation of a "screened" electrostatic ion trap for analysis of high mass molecules by fourier transform mass spectrometry. AB - With the recent adaptation of matrix-assisted laser desorption/ionization (MALDI) of large biomolecules and polymers to Fourier transform mass spectrometric analysis, it is of interest to explore the possible advantages of using a "screened" electrostatic ion trapping technique. It is demonstrated that the observed rate of change of ion cyclotron resonance frequency with trapping potential is in excellent agreement with theory, being independent of mass and charge, in the mass range from 1185 to just under 17,000 Da. When a screened cubic trap is used in a ca. 7-T magnetic field, the electrical potential within the trap is effectively reduced, and ion cyclotron resonance frequency shifts as a function of trapping potential are decreased by a factor of 25. There is no evidence of significant improvement in mass resolution with this trap design, except when higher trapping potentials are compared. In a 9.7-V screened trap measurement, a bovine insulin spectrum with an average resolution of 10,000 is obtained. Comparable mass resolution under conventional trapping conditions could not be obtained for trapping potentials greater than 1.2 V. It is evident from this study that use of the screened trap technique could offer advantages for MALDI-Fourier transform mass spectrometry. PMID- 8460833 TI - Dual microcolumn immunoaffinity liquid chromatography: an analytical application to human plasma proteins. AB - Dual-column microcolumn immunoaffinity chromatography was accomplished by coupling immunoaffinity (IAC) and reversed-phase high-performance liquid chromatography (RP-HPLC) analysis columns. The IAC support was prepared by hydrophobically adsorbing the appropriate antibody onto an octyl silica-based stationary phase contained in a 250-microns-l.d. fused-silica microcolumn. Once the antigen was captured, the antigen-subtracted human plasma could be sent to the RP-HPLC microcolumn for plasma profiling. The antigen was quantitated by desorbing it from the IAC column and transferring it to the RP-HPLC system. Human plasma profiles were generated after removal of albumin, and transferrin and alpha 1-antitrypsin were quantitated with nanogram sensitivity. All analyses were accomplished with less than 1 microL of human plasma. PMID- 8460834 TI - [Methodologic aspects of the determination of growth hormone in urine]. PMID- 8460835 TI - [The Navarra study (PECNA). Hyperlipidemia III. Variations in the median HDL levels and lipid risk quotient in children and adolescents based on age and gender]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analyzed in 5,829 children of both sexes. The subjects were between 4 and 17 years of age and were selected at random from the school population in our community. In this article we analyze the variations in HDL-cholesterol and cholesterol/HDL and LDL/HDL risk quotients according to age and sex. Beginning at the age of 10, the HDL decreases in both sexes, although this decrease is more evident among males and they obtain levels lower than those during early childhood. Among females older than 14 there is a slight increase. Apparently the decrease in HDL among male adolescents is due to an increase in the production of testosterone during this stage of life. Both risk quotients decrease until the children are 10 years of age, after which they increase among males and stabilize or slightly decrease among females. For this reason, scores are higher for males during the last years of adolescence. The cardiovascular lipid risk increases with age and during adolescence in higher among males and depends more on the variations in HDL than on variations in cholesterol or LDL. We believe that the best definition for cardiovascular lipid risk during the infancy or adolescents is one which is based on the risk quotients. PMID- 8460836 TI - [The Navarra study (PECNA). Hyperlipidemia IV. Prevalence of hyperlipidemia in the infant- and juvenile population of Navarra. Variations based on age, gender and health care accessibility]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analyzed in 5,829 children of both sexes. These children were between 4 and 17 years of age and were randomly selected from the school population of our community. In this article, we analyze the prevalence of lipid risk, according to its different definitions, among children and adolescents in Navarra, and its variations related to age, sex and sanitary area. The prevalence of hypercholesterolemia (C > 200 mg/dl) among children and adolescents, aged 4 to 17 years, is very high: 21.07% +/- 0.54%. In spite of having high serum levels of HDL, the lipid risk measured by the risk quotient LDL/HDL > 2.2 is still very high: 15-70% +/- 0.49%. If we define the lipid risk during childhood and adolescence by the quotient LDL/HDL > 2.2, male adolescents turn out to be the group with the highest risk. This phenomenon coincides with the results of the epidemiological studies made among adults. Nevertheless, they do not coincide with these results if the lipid risk is defined by C > 200 mg/dl. In our opinion, during infancy and adolescence, the lipid risk is better defined by the quotient LDL/HDL > 2.2. PMID- 8460837 TI - [Long-term results of surgical management of congenital aortic stenosis]. AB - This retrospective study and review of the literature was undertaken to assess the long term results of valvotomy in congenital aortic stenosis (AS). One hundred and seven patients, aged between 14 days and 15 years (mean: 6.2 years), were operated on between 1966 and 1989. Thirty-three cases had valvular AS, 48 discrete subvalvular AS, 10 supravalvular AS and 16 combined AS. Thirty-three patients had associated cardiac anomalies. The surgical mortality was 6.5% (3.5% in children over 2 years of age). Three patients were lost. Ninety-seven patients had a follow-up period between 6 months and 16 years (mean: 5.4 years) with an actuarial survival of 95% at the age of 15 years. There were adverse events in 39 patients: AS, aortic regurgitation, bacterial endocarditis, third-degree heart block. Thirteen patients required re-operation and 4 balloon valvuloplasty; the late mortality was 5%. We conclude that this surgery has a low surgical mortality, but must be considered as palliative in most cases. PMID- 8460838 TI - [Congenital familial cardiopathies. Prenatal diagnosis]. AB - The diagnosis of congenital heart disease by means of echocardiography is already a real fact. The use of this technique for diagnosis in utero currently allows the detection of these malformations during the early stages of pregnancy and to determine the prognosis of the fetal cardiopathies, as well as to establish a medical or surgical treatment of the neonate. The prenatal echocardiographic study of 126 pregnant women, previously having had children with heart disease, has allowed s to prove the greater incidence of cardiopathy in this population (6.4%), compared to the results obtained from a group of pregnant women previously having normal children and without a high risk pregnancy (0.8%). These findings support the theory that genetic factors are the primary cause of congenital cardiac malformations, although the existence of teratogen factors (rubella, diabetes, etc.) in some cases cannot be excluded. PMID- 8460839 TI - [Study of the growth and final body height in a young adult population]. AB - To know the final height of young adults in our environment, we obtained a control group with 340 students of medical and professional training and compared them with the patterns of Hernandez et al. Medium values of weight, height, weight/height rate, and tricipital and subscapular skinfolds are similar in both groups. If we separate them by birth year (1965-1966 and 1970-71), we find significant differences, on behalf of the younger group, in women for weight and weight/height rate (p < 0.05), and in both sexes for skinfolds (p < 0.001). If we separate them by oriing (medicine-professional training), we find significant differences, on behalf of male university students in weight and weight/height rate (p < 0.05) and of female professional students in skinfolds (p < 0.001). We verify the suitability of the tables of Hernandez et al. for the final growth of young people around us and justify their use in the daily practise. PMID- 8460840 TI - [Thyroid cancer in childhood: review of 7 cases]. AB - Thyroid carcinoma in childhood is a rare, but nevertheless malignant disease, with a high incidence of nodal metastasis. Seven children, 6 boys and 1 girl, aged 4 to 9 years with thyroid carcinoma were treated at the Hospital Infantil Valle de Hebron of Barcelona between 1965 and 1990. The diagnosis was established by cervical nodal biopsy in all cases except one. Papillary carcinoma was found in 4 cases, follicular type in 2 cases and one case of mixed carcinoma was diagnosed. Surgical treatment consisted in lobectomy on the affected side, followed by total thyroidectomy on the opposite side and bilateral resection of involved nodes one or more times. In two patients, treatment with sodium-iodine I131 showed active tissue in the thorax and wound. Both were treated effectively. All patients are alive without recurrences during a follow-up period of 1 to 23 years. Main complications were: temporary recurrence of the nerve injury in two patients and a controlled hypoparathyroidism in another two cases. In all cases, treatment with L-thyroxine was required. Thyroid carcinoma in children carries a considerably better prognosis than in adult patients. We must suspect thyroid carcinoma and indicate biopsy in all cases of cervical nodes resistant to antibiotic treatment. Early diagnosis, total thyroidectomy, radioiodine treatment and hormone administration permit radical cure even in the case of metastatic disease. PMID- 8460841 TI - [Gastroesophageal reflux in pediatric neurologic patients]. AB - With the aim of evaluating the incidence of gastroesophageal reflux (GER) in neurologic pediatric patients with severe motor and/or psychiatric involvement, a retrospective study of 140 infants followed at the Neuropediatric Unit was realized. Forty-five patients (32.1%) had moderate to severe mental retardation (ms RR), 21 of these patients had associated tetraparetic cerebral palsy (T-CP). The rest of the infants presented variable degrees of neurologic involvement: 25 diplegic (D-CP), 27 hemiparetic (H-CP), 22 with slight mental retardation or borderline IQ without motor deficit (SMR), and 21 had attention deficit disorder with hyperactivity (ADD-H). The diagnosis of GER was based on clinical symptomatology and barium ingestion with fluoroscopy and/or esophagoscopy. GER was confirmed in 27 patients: 19 (90.5%) with T-CP, 6 (25%) with ms-MR and 2 (8%) with D-CP. The rest of the infants did not have GER. There was a very significant difference in the frequency of GER in the T-CP group with respect to the other groups (p < 0.001) and a significant difference in the ms-MR patients with respect to the other groups (p < 0.05). The treatment of GER was surgical in ten patients (37%), after failure of medical treatment in 8; exclusively medical treatment in 10 cases (37%) and postural and dietetic treatment in 7 (26%) patients. Good control of GER, resulting in an improvement in the quality of life, occurred in 90% of the patients treated surgically and only in 55% of the patients treated medically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460842 TI - [Smoking habits among Bierzo adolescents]. AB - The results of a smoking survey, carried out in the Bierzo area, are reported here. The study group included 403 youngsters, 245 males and 158 females, between the ages of 11 and 20 years. One hundred and sixty-three of the 265 youngsters that had smoked sometimes, continued to smoke, with 93 (23.0%) smoking occasionally and 70 (17.3%) smoking habitually. The proportion of females and males was similar. The mean age of males for their first experience with smoking was 12.6 years and was earlier than that for females (13.7 years). There were less smokers among youngsters from families in a high economic situation (18%), but they formed the group with the highest consumption of tobacco. The smoking habit of the youths was related to the tobacco use of their siblings, but not to that of their parents. A negative relationship was found between efficacy at school and smoking. The was also a high frequency of smokers among habitual drinkers. PMID- 8460843 TI - [Acute lymphoblastic leukemia: comparison of traditional treatment with intensive therapy methods]. AB - In this study we compare two different therapies for the treatment of non-B acute lymphoblastic leukemia (ALL). Forty-four children diagnosed as having non-B ALL were treated by one of two methods: 20 children were treated from 1981 to 1984 according to the PETHEMA 7/78 protocol and 24 children were treated from 1984 to 1987 following the BFM 83 protocol. These treatments differ in that BFM 83 includes a higher number of cytostatics, uses intravenous methotrexate at moderate doses as "reservoirs" treatment and a lower dose of holocranial radiotherapy. The BFM 83 treatment resulted in a significant improvement in survival (48% versus 92% p < 0.05), as well as in the absence of further events (45% versus 88%, p < 0.01). PMID- 8460844 TI - [Sexual and biological maturation]. AB - We have studied the physical characteristics of strength and the electrocardiographs of 291 boys, between 9 and 15 years of age, and 284 girls from 8 to 14 years old, divided into groups according to their sexual maturation stage (SMS). During this age period, children pass from SMS 1 to SMS 5. We have used the Ruffier-Dickson test as a test of strength and have also obtained an electrocardiographic index. Analysis of variance (ANOVA) showed that in girls, the number of hours of sport activity/week, systolic blood pressure (SBP) and diastolic blood pressure (DBP) both during rest and post-effort (SBPe and DBPe), Ruffier-Dickson index (RDI), pressure frequency product (PFP), increase of diastolic blood pressure (Inc DB) and the indices of Lewis and Sokolow right show a statistically significant dependence on the SMS. In boys, the number of hours of sport activity/week, SBP, DBP, heart frequency post-exercise, SBPe, RDI, PFP, increase in systolic blood pressure and the index of Sokolow right and left are dependent on the SMS. The objective of this paper is to draw the pediatrician's attention to the need to use the SMS for evaluating biological functions, not the chronological age. PMID- 8460845 TI - [Central venous access in pediatric patients. A 6-year experience]. AB - The need for an access to the venous system, in order to infuse chemotherapeutic treatments or parenteral nutrition, has increased the number of central venous access systems (CVAS) implanted in the past years. Between February 1985 and December 1990, 87 devices were implanted in 76 patients (from 11 months to 15 years of age), with a median function time of 349 days (range: 7 to 1887 days). The overall incidence of complications was 0.10 per 10 days of catheterization, with complication rates for infection and thrombosis of 0.02 and 0.03, respectively. Nineteen systems were removed because of complications and 11 because of completion of the treatment. Of the cases, 97.7% included a follow-up period. The present study confirms the advantages of these devices, with a long working life and a low complication rate, being a good alternative for chronically ill children requiring long-term and/or cyclic intravenous therapy. PMID- 8460846 TI - [Anomalous origin of the left coronary artery from the pulmonary artery: echocardiographic diagnosis in an asymptomatic infant]. PMID- 8460847 TI - [Spontaneous reactivation of chronic hepatitis due to hepatitis B infection in a child]. PMID- 8460848 TI - [Value of echography in the early detection of osteomyelitis in childhood. Apropos of a case]. PMID- 8460849 TI - [Panniculitis associated with alpha 1-atitrypsin deficiency]. PMID- 8460850 TI - [Neonatal multifocal osteomyelitis caused by Serratia marcescens. 10-year evolution of a case]. PMID- 8460851 TI - [A case of neonatal Pallister-Killian syndrome (tetrasomy 12p)]. PMID- 8460852 TI - [Spondylodiscitis in childhood: study of 7 patients]. PMID- 8460853 TI - Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group. AB - OBJECTIVE: To determine the factors associated with appendicular bone mass in older women. DESIGN: Cross-sectional analysis of baseline data collected for a multicenter, prospective study of osteoporotic fractures. SETTING: Four clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela valley, Pennsylvania. PATIENTS: A total of 9704 ambulatory, nonblack women, ages 65 years or older, recruited from population-based listings. MEASUREMENTS: Demographic and historical information and anthropometric measurements were obtained from a baseline questionnaire, interview, and examination. Single-photon absorptiometry scans were obtained at three sites: the distal radius, midradius, and calcaneus. Multivariate associations with bone mass were first examined in a randomly selected half of the cohort (training group) and were then tested on the other half of the cohort (validation group). RESULTS: In order of decreasing strength of association, estrogen use, non-insulin dependent diabetes, thiazide use, increased weight, greater muscle strength, later age at menopause, and greater height were independently associated with higher bone mass. Gastric surgery, age, history of maternal fracture, smoking, and caffeine intake were associated with lower bone mass (all P < 0.05). For example, we found that 2 or more years of estrogen use was associated with a 7.2% increase in distal radius bone mass, whereas gastrectomy was associated with an 8.2% decrease in bone mass. The associations between bone mass and dietary calcium intake and rheumatoid arthritis were inconsistent. Alcohol use, physical activity, use of calcium supplements, pregnancy, breast-feeding, parental nationality, and hair color were among the many variables not associated with bone mass. Multivariate models accounted for 20% to 35% of the total variance of bone mass. CONCLUSIONS: A large number of factors influence the bone mass of elderly women; however, age, weight, muscle strength, and estrogen use are the most important factors. PMID- 8460854 TI - Prediction of cardiovascular death in men undergoing noninvasive evaluation for coronary artery disease. AB - OBJECTIVE: To develop prediction rules from clinical and exercise test data identifying patients at high and low risk for cardiovascular events among a group of male veterans. DESIGN: Prognostic study with prospective gathering of data and routine follow-up of consecutive patients referred for exercise testing. Patients only underwent noninvasive evaluation for coronary artery disease. No validation cohort is yet available. SETTING: A 1200-bed Veterans Affairs Medical Center. PATIENTS: Of 3609 men referred for exercise testing between 1984 and 1990, 2546 patients remained evaluable after exclusion of those who underwent subsequent cardiac catheterization, those with significant valvular heart disease, and those who had previous coronary artery bypass surgery. MEASUREMENTS: Evaluation included recording of clinical data on a standardized form and a standard treadmill test followed by assessment of cardiovascular events. RESULTS: During a mean follow-up period (+/- SD) of 2.75 (+/- 18) years, 119 cardiovascular deaths and 44 nonfatal myocardial infarctions occurred in 2546 patients. The Cox proportional hazards model showed the following characteristics to be statistically independent predictors of time until cardiovascular death: history of congestive heart failure or digoxin use, exercise-induced ST depression, change in systolic blood pressure during exercise, and exercise capacity. Using a simple score based on one item of clinical information (history of congestive heart failure or digoxin use) and three exercise test responses (ST depression, exercise capacity, and change in systolic blood pressure), 77% of patients were categorized as low risk (annual cardiac mortality rate, less than 2%), 18% as moderate risk (annual cardiac mortality rate, 7%), and 6% as high risk (annual cardiac mortality rate, 15%; hazard ratio, 10; 95% confidence interval, 6 to 17). This model has not yet been validated. CONCLUSIONS: Variables available from the usual non-invasive work-up of patients with known or suspected coronary artery disease can be used to predict future risk for cardiovascular death. PMID- 8460855 TI - Radiation pneumonitis: a possible lymphocyte-mediated hypersensitivity reaction. AB - OBJECTIVE: To determine if unilateral thoracic irradiation results in a lymphoid alveolitis in both irradiated and unirradiated lung fields. DESIGN: A prospective, nonrandomized study. PATIENTS: Women receiving postoperative radiotherapy for carcinoma of the breast were evaluated both before and 4 to 6 weeks after radiotherapy. Findings after radiotherapy in 15 asymptomatic patients were compared with findings in a group of patients with clinical radiation pneumonitis. MEASUREMENTS: History, physical examination, chest radiograph, quantitative gallium lung scanning, respiratory function tests, bronchoalveolar lavage, and lavage lymphocyte subset analysis. RESULTS: After irradiation, lavage lymphocytes increased significantly (34.5% versus 46.8%; P = 0.01) in the 17 patients studied prospectively. There was an associated reduction in vital capacity (102.5% versus 95.5%; P = 0.04). Comparison of results in patients before treatment, after treatment without clinical pneumonitis, and after treatment with clinical pneumonitis showed a dramatic increase in total lymphocytes after irradiation (6.3 versus 9.4 versus 35.2 million, respectively; P = 0.005), particularly in those with clinical pneumonitis. Only in those with clinical pneumonitis was this accompanied by an increase in the gallium index (3.7 versus 3.4 versus 9.0, respectively; P < 0.001). Vital capacity was also progressively reduced (102.5% versus 96.9% versus 76.7%, respectively; P = 0.04), as was diffusing capacity (98.6% versus 91.4% versus 72.6%, respectively; P = 0.003). No statistical differences existed between irradiated and unirradiated sides of the chest in either lavage or gallium lung scan studies. CONCLUSION: In most patients, a lymphocytic alveolitis develops in both lung fields after strictly unilateral thoracic irradiation; this is more pronounced in patients developing clinical pneumonitis. These findings suggest that radiotherapy may cause a generalized lymphocyte-mediated hypersensitivity reaction. PMID- 8460856 TI - Hypopituitarism after tuberculous meningitis in childhood. AB - OBJECTIVE: To study the prevalence and pathogenesis of hypopituitarism following tuberculous meningitis in childhood. DESIGN: A retrospective cross-sectional study. SETTING: A university teaching hospital and a tuberculosis referral center. PATIENTS: Forty-nine patients, aged 23.4 +/- 6.0 years (mean +/- SD), who had tuberculous meningitis in childhood (age at diagnosis, 5.9 +/- 5.0 years) were studied. MEASUREMENTS: A detailed assessment of hypothalamic-pituitary function, including conventional stimulation tests and responses to four hypothalamic releasing hormones, was done. Magnetic resonance imaging of the hypothalamic-pituitary region was performed in patients with abnormal endocrine function. RESULTS: Ten patients were found to have abnormal pituitary function: Seven had growth hormone deficiency, four of whom also had gonadotropin deficiency; the other three had gonadotropin deficiency, corticotropin deficiency, and mild hyperprolactinemia, respectively; none had diabetes insipidus. Among those with growth hormone deficiency, a significant correlation (r = 0.749, P < 0.05) was found between the height standard deviation score and the age at diagnosis of tuberculous meningitis. Growth hormone, corticotropin, and gonadotropin responses to growth hormone releasing hormone, corticotropin releasing hormone, and gonadotropin releasing hormone, respectively, suggested a hypothalamic defect in five patients. Magnetic resonance imaging scans of the hypothalamic-pituitary region were abnormal in five patients. CONCLUSIONS: Hypopituitarism was documented in 20% of a small subset of patients years after recovery from tuberculous meningitis in childhood. The cause appears to be tuberculous lesions affecting the hypothalamus, pituitary stalk and, directly or indirectly, the pituitary itself. Early recognition and treatment can be beneficial. PMID- 8460857 TI - Spontaneous pneumothorax in patients with leukemia: first sign of invasive mycosis? PMID- 8460858 TI - Isolated right ventricular myocardial infarction. PMID- 8460859 TI - Atherosclerotic renovascular disease and progressive renal failure. AB - PURPOSE: To evaluate information on the prevalence and rate of progression of atherosclerotic renovascular disease and the effect of angiotensin-converting enzyme inhibition on this process, with the goal of developing a rational approach to the diagnosis and management of this disorder. DATA SOURCES: Relevant articles were identified from the authors' files and from MEDLINE searches. Additional references were obtained from the bibliographies of identified articles. STUDY SELECTION: Virtually no controlled prospective studies have been reported. The articles presented are primarily retrospective analyses and include those that provide sufficient information about the incidence or progression of renovascular disease and about the outcome and mortality rate associated with various treatments, to allow evaluation. DATA EXTRACTION: For the outcomes of interest, data from individual reports are presented in tabular form, the results summed, and averages obtained. RESULTS: Atherosclerotic renovascular disease, in many cases involving both renal arteries, is a common finding in patients older than 50 years, particularly those with diffuse atherosclerotic vascular disease. Hypertension is not a particularly sensitive indicator of this disease (almost one half are not hypertensive). The disease progresses and may account for 5% to 15% of all patients developing end-stage renal disease each year. Angiotensin converting enzyme inhibition may damage ischemic renal tissue, but this is counterbalanced by beneficial effects of this therapy. Once end-stage renal disease is present, mortality rates are high despite dialysis support (> 50% over 3 years). Both surgery and angioplasty can preserve or improve renal function and may delay or prevent the need for dialysis therapy. These invasive procedures may have lower rates of morbidity and mortality than the so-called "conservative" approach of dialysis therapy when renal failure develops. CONCLUSIONS: Given available information, diagnosis and intervention should be considered seriously in patients at high risk for renovascular disease who have clearly progressing renal insufficiency. Prospective trials are needed, however, to determine the costs and benefits of each approach to treatment in all patients with renovascular disease and renal insufficiency. PMID- 8460860 TI - NIH conference. New insights into common variable immunodeficiency. AB - Common variable immunodeficiency (CVI) is a heterogenous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome also have an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by various medical specialists. This review discusses the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI. PMID- 8460861 TI - More informative abstracts of articles describing clinical practice guidelines. AB - Recommendations are proposed for preparing more informative abstracts of articles describing clinical practice guidelines. Information about the development and content of guidelines should be summarized with the following structure. OBJECTIVE: a succinct statement of the objective of the guideline, including the targeted health problem, the targeted patients and providers, and the main reason for developing recommendations concerning this problem for this population. OPTIONS: principal practice options that were considered in formulating the guideline. OUTCOMES: significant health and economic outcomes identified as potential consequences of the practice options. EVIDENCE: Methods used to gather, select, and synthesize evidence, and the date of the most recent evidence obtained. VALUES: persons and methods used to assign values (relative importance) to potential outcomes of alternative practice options. BENEFITS, HARMS, AND COSTS: the type and magnitude of the main benefits, harms, and costs that are expected to result from guideline implementation. RECOMMENDATIONS: a brief and specific list of key recommendations. VALIDATION: the results of any external review, comparison with guidelines developed by other groups, or clinical testing of guideline use. SPONSORS: key persons or groups that developed, funded, or endorsed the guideline. Abstracts adhering to these recommendations could enhance readers' ability to appraise the applicability, importance, and validity of guidelines for specific providers, patients, and settings. More informative abstracts could also promote the use of more explicit methods of guideline development, more consistent reporting of guideline documents, and the more appropriate use of guidelines by clinicians. PMID- 8460862 TI - A birth in Tedda. PMID- 8460863 TI - Risk factors for low bone mass: clinical implications. PMID- 8460864 TI - The breast cancer screening controversy continues. PMID- 8460865 TI - The breast cancer screening controversy continues. PMID- 8460866 TI - The breast cancer screening controversy continues. PMID- 8460867 TI - The breast cancer screening controversy continues. PMID- 8460868 TI - Carcinoma of the male breast. PMID- 8460869 TI - Tamoxifen for carcinoma of the male breast. PMID- 8460870 TI - Minocycline-induced pneumonia. PMID- 8460872 TI - Perceptions of chief medical residency. PMID- 8460871 TI - Minocycline-induced pneumonia. PMID- 8460873 TI - Medical informatics and the need for general internists. PMID- 8460874 TI - Positive views of retirement communities. PMID- 8460875 TI - A national cross-sectional study of the working environment in the Danish wood and furniture industry--air pollution and noise. AB - A cross-sectional survey was carried out in the Danish wood and furniture industry at 200 factories. In this paper, representative estimates of employees' full-shift exposures to wood dust, vapours from organic solvents, formaldehyde and noise dose were calculated using a model for two-stage cluster designs. Exposures to air pollutants were generally below the occupational exposure limits (OELs), while noise doses were at the same level as OEL. The overall exposure to wood dust was 0.90 mg m-3, exposure to vapours from organic solvents was 0.13 C/OEL and noise dose, Leq (8 h), was 90.5 dB(A). PMID- 8460876 TI - The evaluation of exposure of printing trade employees to polycyclic aromatic hydrocarbons. AB - Epidemiological studies of the lung cancer experience of workers in the printing industry have been inconclusive. Where there have been positive findings, the effect has generally been attributed to polycyclic aromatic hydrocarbon (PAH) exposure, although no exposure measurements were made. This study was undertaken to determine the exposures of printing press operators to PAH and total particulate (TP), and to evaluate the factors contributing to exposure. Personal time-weighted average exposures of press room workers were determined on two consecutive days at nine sites, including two newspaper operations. The average PAH exposure was 16.5 micrograms m-3 (including naphthalene). The average TP exposure was 0.63 mg m-3. Examination of the data revealed that there were significant differences between sites for exposure both to TP and to PAH. Newspaper plants had significantly lower exposures than commercial printing operations. There were no significant differences in exposure between the various job classifications of workers in the press rooms. Factors identified as contributing to exposure to TP were: the effectiveness of the ventilation systems, the method of feeding the press, the type of paper and the print impression area. PMID- 8460877 TI - The effect of seat suspension on exposure to whole-body vibration of professional drivers. AB - In this study the effectiveness of the seat suspension on the transmission of whole-body vibration through the driver's seat has been determined. Eleven types of seat frequently used in lorries, agricultural tractors and fork-lift trucks were selected. The transmissibility coefficient of each seat was measured by the ratio of the acceleration (weighted root-mean-square in the vertical axis) at the interface between the seat surface and the human body to the vibration at the attachment points of the seat on the vehicle floor. Measurements in the laboratory, using standardized representative vehicle vibration spectra and two volunteers of different weights, showed transmissibility coefficients of 0.34 1.28. Attenuation of the vibration input spectrum was obtained in 20 out of 24 (83%) measurements. Measurements in the field, conducted in vehicles under representative working conditions, showed transmissibility coefficients of 0.60 1.45. Attenuation of the vibration spectrum was obtained in 17 out of 24 (71%) vehicle-seat combinations. No significant differences were observed between seats with conventional suspension and those with air suspension. Laboratory measurements of the dynamic response of the seat suspension did not provide an adequate basis for predicting its performance in the field. In most work situations the magnitude and duration of vibration-exceeded the 8 h fatigue decreased proficiency boundary of 0.32 m s-2 in the vertical axis, which indicates that in many working situations with a daily exposure of 8 h or more suspended seats will not protect professional drivers from harmful exposure to whole-body vibration. PMID- 8460878 TI - Lung cancer in the Schneeberg mines: a reappraisal of the data reported by Harting and Hesse in 1879. AB - The first description of occupational lung cancer, by Harting and Hesse in 1879, unfortunately is not readily accessible. Its account of the vicissitudes of the Schneeberg miners merits study and is therefore presented in summary and set in a historical and geological context. The authors attempted to discover the cause of the disease and made recommendations for improving the health of miners. In the course of their programme of investigations, they developed methods for measuring airborne dust and inhaled dust by personal monitoring. It was left to subsequent discovery for radon and its daughter products to be identified as the causal agents. Later generations were to discover the impact of radioactive spoils from mines situated in the mountain range in which Schneeberg was located. PMID- 8460879 TI - Bronchial reactivity among cotton workers in relation to dust and endotoxin exposure. AB - Bronchial reactivity was measured before work among non-smoking female and male workers from carding, spinning, warping and weaving areas in a cotton mill. Airport baggage loaders were used as controls. The amount of dust and endotoxin was measured at the different workplaces. Statistically significant decreases in FEV1 were found between groups of cotton workers at different work sites after administration of the highest accumulated methacholine dose used (1.25 mg). A relationship was found between decreases in FEV1 after methacholine challenge and airborne endotoxin levels but not for dust. PMID- 8460880 TI - The setting of an occupational exposure limit for phosphamidon in the workplace- a Chinese approach. AB - This paper describes the approach of setting an occupational exposure limit for phosphamidon, an organophosphorus pesticide, in the workplace in China. Apart from a general review of the literature relating to various toxicological studies, special emphasis has been placed on the results of a systematic occupational health survey on the workers exposed to phosphamidon. As a result of the survey, together with the literature review, a 'maximum allowable concentration' (MAC) for phosphamidon in the air of workplace is suggested as 0.02 mg m-3 but on the condition that the route of skin entry be blocked effectively. In addition, based on the description of the standard-setting process in China, a comparison has been made to the current U.K. approach. PMID- 8460881 TI - Renal cell carcinoma metastatic to the orbit: a clinicopathologic report. AB - Renal cell carcinoma (RCC) is a tumor of middle-aged men that metastasizes to the lung, liver, and bone. Few cases of RCC metastatic to the orbit have been reported. When this tumor spreads to the orbit, the orbital metastasis is likely to be the first indication of the cancer. We report the case of a 53-year-old man with widespread metastatic RCC whose first sign of disease was a metastatic orbital tumor. External and ocular examination and computed tomographic and histopathologic findings are described. The clinical characteristics, treatment, and prognosis of metastatic RCC are discussed. PMID- 8460882 TI - Hemicentral retinal vein occlusion associated with ocular hypertension and clotting abnormality. AB - Hemicentral retinal vein occlusion in a young adult man occurred after a high corticosteroid-induced increase in intraocular pressure (IOP), supporting the accepted association between raised IOP and retinal vein occlusion. However, detection of a plasminogen activator deficiency in this patient indicated a particular susceptibility to intravascular clotting episodes. PMID- 8460883 TI - The correction of diplopia after cataract extraction. AB - The records of 12 patients with persistent diplopia after cataract extraction were reviewed. All patients were corrected surgically using an adjustable-suture technique. After strabismus surgery, the diplopia in nine of the 12 patients resolved without adjunctive therapy. Three patients had occasional diplopia postoperatively. Prismatic correction postoperatively was unwarranted in two patients because diplopia occurred on rare occasions, but the third required postsurgical prismatic correction with improvement. PMID- 8460884 TI - Isolated ocular involvement in non-Hodgkin's lymphoma with immunocytochemical evaluation. AB - We report the case of a patient with isolated ocular involvement and non Hodgkin's lymphoma (also known as reticulum cell sarcoma). Most non-Hodgkin's central nervous system lymphomas are large cell lymphomas derived from B-cells. The patient initially had iritis OD and vitreous cells OS. Eventually, rubeosis and vitritis developed OD. A systemic workup showed no extraocular lymphoma. Immunocytochemical analysis was done on the vitreous OD and detected a monoclonal B-cell population of large lymphoid cells. This case shows the frequent delay in making the diagnosis of this condition. This diagnosis must be remembered when a patient has vitreous opacities. PMID- 8460885 TI - Computed tomography and magnetic resonance imaging in the diagnosis of posterior scleritis. AB - The clinical records of 14 patients with posterior scleritis were reviewed to compare the diagnostic potential of computed tomography (CT) and magnetic resonance imaging (MRI) in this condition. None of these patients had evidence of collagen vascular or other systemic diseases. Done 13 times on 11 patients, CT was diagnostic for posterior scleritis in six patients on seven occasions. We used MRI six times in five patients, and it was not diagnostic for posterior scleritis in any patient. Thus, CT appeared to be more sensitive than MRI in the diagnosis of posterior scleritis. The CT results appeared comparable to ultrasonographic findings (obtained eight times in six patients) in the diagnosis of posterior scleritis. Both CT and MRI, however, detected signs of orbital pseudotumor in six and three patients, respectively. These findings support the concept that posterior scleritis and orbital pseudotumor may represent a continuum of the same disease process. PMID- 8460887 TI - Integrative systems research on the brain: resurgence and new opportunities. PMID- 8460886 TI - Endogenous endophthalmitis caused by Escherichia coli. AB - Endophthalmitis is a rare complication of Escherichia coli-induced septicemia. Nine cases of endogenous endophthalmitis caused by E. coli have been reported previously, all except one in patients with diabetes. The most common primary site of infection is the urinary tract. The course of illness is rapidly progressive with a poor visual prognosis. Concurrent systemic morbidity, including body abscesses and endocarditis, is high. We report an additional case of endogenous endophthalmitis from E. coli in a diabetic woman. Enucleation was required despite aggressive topical and systemic treatment. The pertinent literature is reviewed. PMID- 8460888 TI - Molecular control of cell fate in the neural crest: the sympathoadrenal lineage. AB - Over the past five years, new insights have been gained into the biology of the SA lineage. These advances have been powered by the development of immunologic methods to isolate embryonic SA progenitors from fetal adrenal glands and sympathetic ganglia. Analysis of these embryonic progenitors has confirmed many of the ideas derived from earlier studies of postnatal cells, but has necessitated several revisions in our thinking, as well. First, embryonic SA progenitors appear to be distinct from mature SIF cells, a cell type initially postulated to be the central intermediate in the SA lineage. Second, FGF, not NGF, appears to be an important early influence on neuronal fate; NGF responsiveness appears relatively late in differentiation. Third, the development of both sympathetic neurons and adrenal chromaffin cells is not a one-step process, but rather involves a series of events, in which the cells change their responsiveness to growth factors and glucocorticoids. Fourth, emerging circumstantial evidence suggests that SA progenitors may have additional developmental potentials. Finally, new insights have been gained into the molecular mechanisms that underlie both the differentiation of SA progenitors and their determination from earlier multipotent neural crest cells. These advances have made the SA progenitor a well-defined system for studying the molecular control of cell fate in a vertebrate neurogenic precursor cell. The analysis of the SA lineage at the cell biological level has raised several interesting molecular questions for future investigation. In the neuronal branch of the SA lineage, how is the acquisition of NGF-responsiveness and NGF-dependence controlled, and what is the relationship of these events to the expression of p140trk and p75? In the chromaffin branch of the pathway, which molecules control the timing of PNMT expression? In the uncommitted SA progenitor, what is the molecular basis of the antagonism between the competing neuronal and chromaffin pathways of differentiation, and how does commitment to neuronal differentiation occur? Can SA progenitors differentiate to enteric neurons in vitro, and which differentiation and survival factors control this phenotype, as well as the other classical neurotransmitter and neuropeptide phenotypes expressed by SA derivatives? What are the roles of MASH1 and other regulatory genes in controlling early stages in neural crest cell determination, and how is the expression of these molecules in turn controlled? How much of the genetic regulatory network controlling neuronal differentiation in Drosophila has been conserved in vertebrates?(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8460889 TI - Implicit memory: a selective review. PMID- 8460890 TI - The neurofibromatosis type 1 gene. PMID- 8460891 TI - The role of NMDA receptors in information processing. AB - In this review, we have concentrated on the parallels between the cellular properties of the NMDA receptor and a variety of functional properties within sensory and motor systems. Of course, the NMDA channel exists within the cell in conjunction with a variety of other channels, including non-NMDA channels. Although the NMDA receptor is unique in a cellular sense--it is the only ligand gated channel that is also voltage dependent and calcium permeable--it is not unique in a functional sense. A cell that has non-NMDA receptors and voltage sensitive channels will also exhibit nonlinear behavior. Moreover, Buhrle & Sonnhof (1983) demonstrated some time ago that calcium flows into frog motor neurons through more than one type of calcium channel. The contribution to the inflow of calcium from NMDA channels may vary from cell to cell and could easily be a minor proportion of the total. Many authors have pointed out that the NMDA channel has a low conductance at a resting potential of -70 mV. However, many cells in the nervous system are depolarized from -70 mV by excitatory input. Thus, as pointed out above. NMDA receptors make a contribution to the tonic or spontaneous activity of cells in both visual cortex and spinal cord. In practice, many cells are probably working in a range of membrane potentials where the NMDA channels are always open to some extent. Even in the hippocampal slice where a substantial amount of afferent input is removed, NMDA receptors contribute to spontaneous activity (Sah et al 1989). Does the NMDA receptor act as a switch? Does it act as an AND gate? The suggestion that it may act as a switch comes from work on LTP in the hippocampus, which is readily produced by high-frequency stimulation and is abolished by APV. However, activation of the NMDA receptor is only the first in a sequence of reactions leading to LTP: In theory, switch-like behavior could also be produced by calcium-buffering systems within dendritic spines, or by enzymatic processes (Lisman 1985; Zador et al 1990). Fox & Daw (1992) have modeled the action of NMDA and non-NMDA receptors that are activated in parallel with each other, and shown that the occurrence of switch-like behavior depends on the relative density of NMDA versus non-NMDA receptors. Switch-like behavior is not seen in the visual cortex, but might be seen in the hippocampus if the relative density of NMDA receptors there was higher than in the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8460892 TI - Processing of temporal information in the brain. PMID- 8460893 TI - Inferior temporal cortex: where visual perception meets memory. PMID- 8460894 TI - Common principles of motor control in vertebrates and invertebrates. PMID- 8460895 TI - Recent advances in the molecular biology of dopamine receptors. PMID- 8460896 TI - Molecular mechanisms of developmental neuronal death. AB - Data derived from several experimental approaches demonstrate that naturally occurring neuronal death during development has many parallels with the physiologically appropriate death seen in nonneuronal cells. Physiologically appropriate death in different cell types may share some common mechanisms. These general notions must remain vague and tentative, because details of the mechanisms by which cells die in response to physiological positive or negative signals are poorly understood in any cell type. Current thinking focuses on the idea that cells possess a mechanism, which involves specific gene products, that are designed to kill the cell in response to appropriate physiological signals. Genetic studies of cell death in C. elegans and the demonstrations of increased expression of specific genes temporally associated with death in nonneuronal cells are consistent with this view. However, in the latter studies, there is no direct evidence that such temporally related genes are critical to the process of cell death or whether such gene expression may be related to somE other aspect of the response to the hormonal manipulations that produce the death of the cell under study. Therefore, the mechanism of death of any cell type is not understood, and whether neuronal death during development or after experimental manipulation results from the same mechanism is unknown. Several approaches are currently being pursued in a number of laboratories to address this general problem. These include pharmacological studies, such as described above, and studies aimed at analyzing biochemical and morphological changes associated with death. Attempts to find mRNAs or proteins whose increased expression is associated with neuronal death can be addressed by subtractive and differential hybridization strategies, by two-dimensional protein gel electrophoresis, and by examining genes whose increased expression is temporally correlated with cell death. Success in these various strategies will provide an understanding of neuronal death and relate to it cell death in other cell types. If future work provides direct evidence for a genetic program acting physiologically to produce death in the developing nervous system, an obvious question becomes the possible role that loss of transcriptional control of such a program plays in the adult in responses to mechanical or chemical trauma, neurodegenerative disease, or neuronal attrition associated with aging. Studies addressing the basic developmental process of trophic factor deprivation-induced death should provide molecular markers of and pharmacological approaches to these pathological processes in the adult. PMID- 8460898 TI - How parallel are the primate visual pathways? PMID- 8460897 TI - Molecular basis of neural-specific gene expression. PMID- 8460899 TI - Glial boundaries in the developing nervous system. PMID- 8460900 TI - Genetic and cellular analysis of behavior in C. elegans. PMID- 8460901 TI - The processing of single words studied with positron emission tomography. PMID- 8460902 TI - Modeling of neural circuits: what have we learned? PMID- 8460903 TI - Neuroanatomy of memory. PMID- 8460904 TI - Behaviorally based modeling and computational approaches to neuroscience. AB - The almost incredible advances that have recently occurred in the power of computers available to scientists in all disciplines have encouraged an explosion of neural network and behavioral models. Some of these have been constrained more by the imagination of the programmer than by rude biological facts. Their relevance for the experimental neuroscientist thus varies from case to case. Some models (e.g. Grillner's model of lamprey swimming movements) are so closely based on known neuroanatomy and neurophysiology that it becomes possible to generate and test precise experimental predictions. Other models (such as MURPHY and NOMAD) use neurobiological principles in their architectures, but do not portray any particular organism. Although it is harder to relate the study of these models of the study of real animals, they fulfill an important explanatory role. They make possible insights into how behavior is controlled by neuronal activity that would be unobtainable in real animals using present methods. Thus, even the excesses of neural modeling have provided a useful impetus to what is undoubtedly a most promising approach to integrating data from the various disciplines concerned with behavior and the mind. The problems have been pointed out by many authors (see citations in our introduction), and a phase of more critical evaluation appears to have begun. We hope that our brief survey of models based on widely different theoretical approaches, but all aimed at explaining behavior, will encourage critical comparisons to be made. As in more mature fields, such as thermodynamics, we can expect that more complete models will force an evaluation of theoretical hypotheses against the entire body of available evidence, rather than just a few pertinent test cases. Such evaluation will make possible a much more rigorous exclusion of invalid or inconsistent theoretical ideas. From such studies, a much smaller, but more robust, set of basic principles can be expected to emerge. From the perspective afforded by our own modeling studies, it appears essential that modeling be informed by a general theory of brain function. In this work, the theory of neuronal group selection provides a useful basis for further work by virtue of its consistency with basic evolutionary and physiological principles and the power of the selection paradigm to shape neural networks in behaviorally adaptive directions. PMID- 8460905 TI - Computational models of the neural bases of learning and memory. PMID- 8460906 TI - Patterning the brain of the zebrafish embryo. PMID- 8460907 TI - Protein targeting in the neuron. PMID- 8460908 TI - Discovery and development of new antibiotics: the problem of antibiotic resistance. PMID- 8460909 TI - In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative. AB - T-3761, a new quinolone derivative, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.20 to 100 micrograms/ml against gram-positive bacteria, including members of the genera Staphylococcus, Streptococcus, and Enterococcus; 0.025 to 3.13 micrograms/ml against gram negative bacteria, including members of the family Enterobacteriaceae and the genus Haemophilus; 0.05 to 50 micrograms/ml against glucose nonfermenters, including members of the genera Pseudomonas, Xanthomonas, Acinetobacter, Alcaligenes, and Moraxella; 0.025 micrograms/ml against Legionella spp.; and 6.25 to 25 micrograms/ml against anaerobes, including Bacteroides fragilis, Clostridium difficile, and Peptostreptococcus spp. The in vitro activity of T 3761 against these clinical isolates was comparable to or 2- to 32-fold greater than those of ofloxacin and norfloxacin and 2- to 16-fold less and 1- to 8-fold greater than those of ciprofloxacin and tosulfoxacin, respectively. When administered orally, T-3761 showed good efficacy in mice against systemic, pulmonary, and urinary tract infections with gram-positive and gram-negative bacteria, including quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa. The in vivo activity of T-3761 was comparable to or greater than those of ofloxacin, ciprofloxacin, norfloxacin, and tosufloxacin against most infection models in mice. The activities of T-3761 were lower than those of tosufloxacin against gram-positive bacterial systemic and pulmonary infections in mice but not against infections with methicillin-resistant Staphylococcus aureus. The activities of T-3761 against systemic quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa infections in mice were 2- to 14-fold greater than those of the reference agents. PMID- 8460910 TI - Effects of two magainin peptides on eicosanoid release from rat peritoneal macrophages. AB - Magainins are novel polycationic peptides with broad-spectrum antimicrobial activity, including activity against gram-negative bacteria. Gram-negative bacteremia can elicit endotoxic shock that is associated with the increased formation of eicosanoids. Inhibition of eicosanoid synthesis has been shown to improve the outcome of experimental endotoxic shock. The aim of the present study was to test the in vitro effects of two magainin peptides, MSI-97 (M1) and MSI-98 (M2), on eicosanoid synthesis by rat peritoneal macrophages (M phi) stimulated by Salmonella enteritidis lipopolysaccharide (LPS; 50 micrograms/ml) and Salmonella minnesota lipid A (5 micrograms/ml) and to compare their effects on LPS reactivity with a metachromatic dye. M1 (100 micrograms/ml) significantly (P < 0.05) reduced LPS-stimulated synthesis of thromboxane B2 (TXB2), without changing 6-keto-prostaglandin F1 alpha in M phi. Similarly, M2 (10 micrograms/ml) significantly attenuated M phi synthesis of TXB2 stimulated by either LPS or lipid A. However, at a higher concentration (100 micrograms/ml), M2 but not M1 significantly augmented LPS-induced increases in TXB2 and 6-keto-prostaglandin F1 alpha. Polymyxin B (40 micrograms/ml) inhibited LPS production and lipid A stimulated TXB2 production. M1 (100 micrograms/ml) and polymyxin B (10 and 40 micrograms/ml) also inhibited calcium ionophore A23187 (10 microM)-induced synthesis of TXB2. The lipid A moiety of LPS reacts with dimethylmethylene blue dye, providing a metachromatic assay of LPS. This metachromatic reaction with lipid A was significantly reduced by polymyxin B and M2 at all concentrations. M1 was effective only at the highest M1:lipid A concentration ratio (2:1). Thus, M1 and M2 share some similarities with polymyxin B in inhibiting lipid A reactivity with the dye, which suggests that these magainins may also bind to lipid A. However, M1 was devoid of any inhibitory effects on dye reactivity with S. enteritidis LPS and M2 was inhibitory at only one concentration ratio (1:5). In conclusion, the varied effects of the magainin peptides on LPS, lipid A, and M phi eicosanoid synthesis appear to depend on the type of peptide used and on its concentration. PMID- 8460911 TI - Molecular basis of rifampin resistance in Mycobacterium leprae. AB - Rifampin is currently the most potent drug used in leprosy control programs. We show that the rifampin resistance which emerged in nine patients with lepromatous leprosy, who had received rifampin monotherapy, stemmed from mutations in the rpoB gene, which encodes the beta subunit of RNA polymerase of Mycobacterium leprae. In eight cases missense mutations were found to affect a serine residue, Ser-425, while in the remaining mutant a small insertion was found close to this site. These findings will be of use for the development of a rapid screening procedure, involving the polymerase chain reaction, for monitoring the emergence of rifampin-resistant M. leprae strains. PMID- 8460912 TI - Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique. AB - Few data exist concerning the effect of obesity on the pharmacokinetic parameters of vancomycin. The purpose of this investigation was to assess the effect of obesity on vancomycin pharmacokinetic parameters in 95 nonobese and 135 obese adult patients (age range, 18 to 92 years) receiving vancomycin. All subjects had normal renal function as defined by a creatinine concentration in serum of < or = 1.5 mg/dl (mean estimated creatinine clearance +/- 1 standard deviation, 76 +/- 34; range, 23 to 215 ml/min). Vancomycin concentrations in serum were determined by the fluorescence polarization immunoassay. All data for vancomycin concentration in serum versus time for each course of therapy were fitted by using a two-compartment Bayesian forecasting program. Subjects were stratified into nine groups on the basis of the percent difference between actual body weight (ABW) and lean body weight (LBW) (> -10%, -10 to 0%, > 0 to 10%, > 10 to 20%, > 20 to 30%, > 30 to 40%, > 40 to 50%, > 50 to 60%, > 60%). Analysis of variance with post hoc Scheffe's testing revealed that statistically significant differences occurred in terminal disposition half-life (t1/2 beta) between the extremes of modestly obese (group 4) and morbidly obese (group 9, P < 0.05) patients. Similar analysis with distribution volume (V) identified significant differences in patients at or near their LBW (groups 2 to 4) and patients who were morbidly obese (groups 8 and 9, P < 0.05). Multiple regression models for the pharmacokinetic parameters V, t1/2beta, and vancomycin total body clearance were developed to assess the joint predictive power of LBW, ABW, and percent over LBW, controlling for the effects of age, initial creatinine concentration in serum, initial creatinine clearance, and gender. In the final model for V, both ABW and percent over LBW were independent and significant predictors. For total body clearance, only ABW was significant and predictive. Percent over LBW was a significant and independent predictor of t1/2beta. LBW is not predictive of these pharmacokinetic parameters and should not be used for initial dosing. On the basis of these data, ABW appears to be superior to LBW for calculating initial dose requirements for vancomycin. PMID- 8460913 TI - Multiple-dose pharmacokinetics of 12 milligrams of trimethoprim and 60 milligrams of sulfamethoxazole per kilogram of body weight per day in healthy volunteers. AB - The disposition of 12 mg of trimethoprim and 60 mg of sulfamethoxazole per kg of body weight in six healthy male volunteers is described. The daily dose was evenly divided and administered orally every 6 h for 13 consecutive doses. Individual drug components were assayed by high-performance liquid chromatography. Steady-state concentrations in serum for trimethoprim and sulfamethoxazole were within the purported therapeutic ranges for treating Pneumocystis carinii pneumonia. Co-trimoxazole was well tolerated, and no subject withdrew from the study because of toxicity. Comparison of the pharmacokinetic parameters in this study with those of our previous findings indicates that the elimination of trimethoprim-sulfamethoxazole follows a first-order process within the dose ranges assessed. Administration of 15- to 20-mg/kg trimethoprim and 75- to 100-mg/kg sulfamethoxazole in four evenly divided doses for the first 24 h followed by 12 and 60 mg/kg/day, respectively, for the remainder of therapy rapidly attains concentrations in serum within the proposed P. carinii pneumonia therapeutic range. Clinical trials are indicated to evaluate this dosing scheme, which may decrease exposure to potentially excessive concentrations of trimethoprim and sulfamethoxazole. PMID- 8460914 TI - Mechanism of uptake of deglucoteicoplanin amide derivatives across outer membranes of Escherichia coli and Pseudomonas aeruginosa. AB - Teicoplanin is a glycopeptide antibiotic which is ineffective against gram negative bacteria because of its inability to penetrate the outer membrane. Removal of the sugar residues and attachment of polyamines to carbon 63 yielded two dibasic deglucoteicoplanin amides, MDL 62,766 (766) and MDL 62,934 (934), with moderate MICs for Escherichia coli (2 to 4 micrograms/ml) and Pseudomonas aeruginosa (8 to 32 micrograms/ml) compared with those of the monobasic teicoplanin aglycone (16 and > 1,024 micrograms/ml, respectively). MICs were increased 16- to 32-fold by Mg2+ supplementation of Luria broth but not by Na+ supplementation at an equivalent ionic strength. Both 766 and 934 were capable of binding to P. aeruginosa lipopolysaccharide (LPS) at Mg(2+)-binding sites, as assessed by dansyl polymyxin displacement experiments. Furthermore, both compounds increased E. coli and P. aeruginosa outer membrane permeability to the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN), whereas the parent compounds teicoplanin aglycone and teicoplanin and the beta-lactam ceftazidime were totally ineffective. Addition of 1 mM Mg2+ blocked the increase in outer membrane permeability. Compound 766 had a lower MIC than 934 for both bacteria tested, bound to LPS with a higher affinity, and permeabilized outer membranes to NPN at lower concentrations. We propose that both deglucoteicoplanin amides exhibit increased gram-negative activity by virtue of their ability to access the self-promoted uptake pathway across the outer membrane. PMID- 8460915 TI - Multiple-dose pharmacokinetics of amikacin and ceftazidime in critically ill patients with septic multiple-organ failure during intermittent hemofiltration. AB - The pharmacokinetic parameters of amikacin and ceftazidime were assessed in four patients undergoing hemofiltration for septic shock. The parameters were assessed during hemofiltration and in the interim period. The concentration-time profiles of these two drugs in plasma, urine, and ultrafiltrate were investigated after intravenous perfusion (30 min). In all cases a 1-g dose of ceftazidime was administered; for amikacin, the dosage regimen was adjusted according to the patient's amikacin levels (250 to 750 mg). Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection for ceftazidime and by enzyme multiplied immunoassay for amikacin. The elimination half-life (t1/2) and the total clearance of amikacin ranged from 31.1 to 138.2 h and from 5.4 to 8.9 ml/min, respectively, during the interhemofiltration period in anuric patients. Hemofiltration substantially decreased the t1/2 (3.5 +/- 0.49 h) and increased the total clearance (89.5 +/- 11.8 ml/min). The hemofiltration clearance of amikacin represented 71% of the total clearance, and the hemofiltration process removed, on average, 60% of the dose. During hemofiltration, the elimination t1/2 of ceftazidime (2.8 +/- 0.69 h) was greatly reduced and the total clearance increased (74.2 +/- 11.2 ml/min) compared with those in the interhemofiltration period (9 to 43.7 h and 7.4 to 16.8 ml/min, respectively). About 55% of the administered dose was recovered in the filtrate, and the hemofiltration clearance of ceftazidime was 46 +/- 14.3 ml/min. A redistribution phenomenon (rebound) in the amikacin and ceftazidime concentrations in plasma (35 and 28%, respectively) was reported after hemofiltration in two patients. The MICs for 90% of the most important pathogens were exceeded by the concentrations of the two drugs in plasma during the whole treatment of these patients. PMID- 8460917 TI - In vitro activities of ceftriaxone and fusidic acid against 13 isolates of Coxiella burnetii, determined using the shell vial assay. AB - The susceptibilities of 13 isolates of Coxiella burnetii to fusidic acid and ceftriaxone were determined by use of the recently described shell vial assay (D. Raoult, H. Torres, and M. Drancourt, Antimicrob. Agents Chemother, 35:2070-2077, 1991). At a concentration of 4 micrograms/ml, ceftriaxone was bacteriostatic for four isolates and slowed the multiplication of the other nine. Fusidic acid at a concentration of 2 micrograms/ml was bacteriostatic for six isolates and slowed the multiplication of three others. These results show that these compounds could be effective in the phagolysosome of C. burnetii-infected cells. PMID- 8460916 TI - Oral enoxacin for infection prevention in adults with acute nonlymphocytic leukemia. The Enoxacin Prophylaxis Study Group. AB - A randomized, double-blind, placebo-controlled trial was conducted in eight hematologic units to determine the efficacy and safety of oral enoxacin for infection prevention in adult patients with acute nonlymphocytic leukemia. One hundred nineteen patients undergoing remission induction or consolidation chemotherapy were enrolled; 62 of them received enoxacin (400 mg orally every 12 h). Patients received antifungal prophylaxis with oral mycostatin (1,000,000 U four times daily) or clotrimazole (1 troche five times daily). Analysis was performed on an intent-to-treat basis. There was no significant difference between groups in race, age, or type and stage of leukemia, but there were more males in the placebo group (P = 0.073 [Fisher's exact test]). Fewer enoxacin patients had gram-negative bacteremia (1 versus 14 [P < 0.001]), gram-negative infection at any site (2 versus 19 [P < 0.001]), or bacterial and/or fungal infection (17 versus 26 [P = 0.056]). There was no significant difference in the number of patients with gram-positive infection at any site (12 versus 16), gram positive bacteremia (9 versus 10), deep fungal infection (6 versus 2), death (2 versus 3), other antimicrobial therapy required (48 versus 48), therapy with amphotericin B (15 versus 7 [P = 0.105]), any adverse event (45 versus 36), or any study drug-associated adverse events (13 versus 6). Logistic regression confirmed (odds ratios and 95% confidence intervals are given in parentheses) that enoxacin reduced the risk of gram-negative infection (0.07; 0.01 to 0.30), especially gram-negative bacillary bacteremia (0.05; 0.01 to 0.37), without altering the risk of gram-positive bacterial (0.63; 0.26 to 1.5), deep fungal (2.57; 0.47 to 13.9), or Clostridium difficile (1.16; 0.3 to 4.56) infection. The median time to the onset of fever of more than or equal 102.8 F (39.3 degree C) was 32 days for the enoxacin group versus 15 days for patients receiving placebo (P=0.0007 [Wilcoxon test]). In patients with acute nonlymphocytic leukemia, oral enoxacin prevents gram-negative infections, delays the onset of fever, does not alter the incidence of gram-positive or proven deep fungal infections, and is well tolerated. PMID- 8460919 TI - Activity of ampicillin-sulbactam and oxacillin in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus. AB - Using a rat model of aortic valve infective endocarditis, we previously found that oxacillin was equally effective against an oxacillin-susceptible strain of Staphylococcus aureus and a beta-lactamase-hyperproducing borderline oxacillin susceptible strain of S. aureus; also, ampicillin-sulbactam was less effective than oxacillin against both isolates and at low doses was less effective against the borderline-susceptible strain than against the fully oxacillin-susceptible strain (C. Thauvin-Eliopoulos, L. B. Rice, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 34:728-732, 1990). In the present study, we extended this work, using alternative treatment schedules and additional bacterial strains. Extending treatment with low doses of ampicillin sulbactam (500 and 250 mg/kg of body weight per day, respectively) to 6.5 days resulted in equalization of effectiveness against the previously studied strains BOSSA-1 and OSSA-1 (3.75 +/- 1.61 log10 and 4.71 +/- 1.79 log10 CFU of residual viable bacteria per g, respectively). Against the borderline oxacillin susceptible strain BOSSA-1, increasing the sulbactam dosage from 500 to 2,000 mg/kg/day while maintaining a fixed dose of ampicillin (1,000 mg/kg/day) by continuous infusion resulted in lower bacterial counts (4.93 +/- 1.84 log10 versus 3.65 +/- 1.26 log10 CFU of residual viable bacteria per g, respectively), but this difference was of only borderline significance; differences in efficacy between the low-dose and high-dose sulbactam regimens were exaggerated when intermittent intravenous administration was used (6.19 +/- 1.90 log10 versus 3.37 +/- 1.41 log10 CFU/g, respectively; P < 0.001). However, for any individual sulbactam dosage, the model of administration (continuous versus intermittent infusion) did not affect the activity of the regimen. When additional strains were used in the model, oxacillin and ampicillin-sulbactam (1,000 plus 2,000 mg/kg/day) were equally effective against both oxacillin-susceptible and borderline oxacillin-resistant strains of S. aureus. These results support the predictions that oxacillin would be clinically effective in the treatment of infections caused by borderline oxacillin-susceptible strains of S. aureus and that, except at very low doses, ampicillin-sulbactam would also be as effective against borderline-susceptible strains as against fully oxacillin-susceptible strains of S. aureus. PMID- 8460918 TI - Pharmacokinetics of intravenous fusidic acid in patients with cholestasis. AB - The pharmacokinetics of fusidic acid and 3-ketofusidic acid were investigated in cholestatic and noncholestatic patients after intravenous administration of single and multiple doses of 500 mg of sodium fusidate. The patients, all with low serum albumin levels, were divided into three groups. Group I consisted of six noncholestatic patients; group II consisted of nine mildly cholestatic patients with mild hepatic impairment (conjugated bilirubin, 47 mumol liter-1; alkaline phosphatase, 280 IU liter-1; gamma-glutamyltranspeptidase, 190 IU liter 1); group III consisted of six benign intrahepatic cholestatic patients with high isolated conjugated hyperbilirubinemia (98.1 mumol liter-1). Assays were performed by high-pressure liquid chromatography. At steady state, the mean peak concentrations in serum were 63.7, 44.9, and 92.2 micrograms ml-1 in groups I, II, and III, respectively; over a dosage interval, areas under the concentration time curve were 411.1, 238.7, and 603.4 micrograms.h ml-1 and the mean body clearances were 0.34, 0.53, and 0.25 ml min kg-1 in groups I, II, and III, respectively. The accumulation ratio of fusidic acid increased from 2.8 and 2.4 in groups I and II to 4.2 in group III. At steady state, the ratios of the areas under the concentration-time curve from 0 to 8 h for 3-ketofusidic acid/fusidic acid were 0.11, 0.09, and 0.10 in the three groups, respectively. Only very small amounts of fusidic acid and 3-ketofusidic acid were found in urine. These results substantiate the following hypotheses. In group I and II patients the clearance is higher than that in healthy volunteers because of the increased free, unbound fraction of fusidic acid, a consequence of lower serum albumin concentrations, resulting in increased distribution in tissue and hepatic metabolism. In group III patients, the higher bilirubinemia results in competition with fusidic acid for the limited glucuronidation, thus compensating for the increased elimination with fusidic acid because of the low serum albumin concentration. These results suggest that fusidic acid can be administered normally even to patients with high bilirubinemia because the postoperative serum albumin concentration is usually low. PMID- 8460920 TI - Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex. AB - Granulocytopenia is a complication of human immunodeficiency virus disease, as well as a toxic manifestation of zidovudine therapy. To evaluate pharmacokinetic and pharmacodynamic relationships, 11 AIDS-AIDS-related complex patients who had developed zidovudine-associated granulocytopenia (mean absolute neutrophil count, 1,077/mm3) were examined after addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to zidovudine. GM-CSF was administered as a daily (1.0 or 0.3 micrograms/kg) or every-other-day (0.3 micrograms/kg) subcutaneous dose over a 28-day period. Zidovudine was continued at the same daily dosage as was previously being administered. Of 11 patients, 7 (1.0 micrograms/kg, n = 5; 0.3 micrograms/kg, n = 2) had a pharmacologic response to GM-CSF with an increase to a mean absolute neutrophil count of 3,189 cells per mm3 at 4 weeks (P < 0.05). The peak concentration of GM-CSF in plasma ranged from 11.5 to 84.4 pg/ml, and the time to peak ranged from 1 to 3 h. No correlation between GM-CSF disposition and hematologic response was noted. A decreased plasma zidovudine glucuronide/zidovudine ratio was noted after 1 week of GM-CSF, and an increase in the area under the plasma concentration-versus-time curve for zidovudine was found in three patients after 4 weeks. Low doses of GM-CSF can raise the granulocyte count in patients with zidovudine-induced neutropenia. The use of GM CSF and zidovudine may represent a viable treatment option for persons with human immunodeficiency virus infection who develop neutropenia while receiving zidovudine but do not tolerate alternative nucleoside analogs. Further studies are needed to assess the complex interaction between these two agents. PMID- 8460921 TI - The fractional maximal effect method: a new way to characterize the effect of antibiotic combinations and other nonlinear pharmacodynamic interactions. AB - The checkerboard technique leading to the fractional inhibitory concentration indexes and the killing curve method are currently the most widely used methods to study antibiotic combinations. For both methods, experimental conditions and interpretation criteria are somewhat arbitrary. The relevance of the fractional inhibitory concentration index computation, in the classic case of additivity [P = d1/(D1)p + d2/(D2)p, where d1 and d2 are the doses of drugs 1 and 2 in combination to produce an effect at a percent level (P) and (D1)p and (D2)p are the doses required for the two respective drugs alone to produce the same effect] relies on the assumption of a linear relationship between the MIC and the concentration of the test antibiotics. In addition, there is no consensus as to the definition of synergy in killing curve interpretation. The fractional maximal effect (FME) method is a new approach which was developed to handle the nonlinear pharmacodynamics exhibited by antibiotics and other drugs. This method relies on the mathematical linearization of the nonlinear concentration-effect scales and eventual construction of an isobologram-type data plot. The FME method was applied to study interactions between several antibiotic combinations: amoxicillin and tetracycline, ciprofloxacin and erythromycin, and ticarcillin and tobramycin. These combinations were selected because the pharmacologic basis for their interactions has been previously described. The FME method correctly identified antagonism for the first two combinations and synergism for the last combination. Conclusions were reproducible across the range of concentrations studied. Besides providing information on the nature of the interaction, the method can rapidly explore the effect of changing concentration ratios of two antimicrobial agents on the degrees of interaction. The FME method may be applied to interactions between drugs or agents with either a linear or nonlinear endpoint measurement. Methods frequently used for drug combination testing are also discussed in the paper. PMID- 8460922 TI - Safety, tolerance, and pharmacokinetics of systemic ribavirin in children with human immunodeficiency virus infection. AB - Eleven pediatric patients, aged 1 to 10 years and with symptomatic human immunodeficiency virus infection, were treated with 6 or 10 mg of oral ribavirin per kg of body weight daily for 60 days. Safety and pharmacokinetic parameters were monitored; five children had comprehensive pharmacokinetic evaluations. The children tolerated the drug well, and treatment was not associated with any clinically significant adverse effects. Peak concentrations in plasma of 2.5 and 3.0 microM were reached at 90 min after single oral doses of 6 and 10 mg/kg, respectively. The mean systemic availability of oral ribavirin was 42.3%. After 60 days of ribavirin administration, mean trough concentrations in plasma of 2.6 and 4.1 microM were obtained. Ribavirin penetrated well into the cerebrospinal fluid, achieving 70% of the concentration in plasma at steady state. PMID- 8460923 TI - Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro. AB - Platelet microbicidal protein (PMP) is released from platelets in response to thrombin stimulation. PMP is known to possess in vitro bactericidal activity against Staphylococcus aureus and viridans group streptococci. To determine whether PMP is active against other intravascular pathogens, we evaluated its potential fungicidal activity against strains of Candida species and Cryptococcus neoformans. Anionic resin adsorption and gel electrophoresis confirmed that the fungicidal activity of PMP resided in a small (approximately 8.5-kDa), cationic protein, identical to previous studies of PMP-induced bacterial killing (M.R. Yeaman, S.M. Puentes, D.C. Norman, and A.S. Bayer, Infect. Immun. 60:1202-1209, 1992). When assayed over a 180-min period in vitro, the susceptibilities of these fungi to PMP varied considerably. Generally, Candida albicans strains (mean survival, 33.5% +/- 6.9% [n = 6]) as well as isolates of Candida glabrata (mean survival, 50.8% +/- 2.9% [n = 2]) were the most susceptible to killing by PMP, while Candida guillermondii and Candida parapsilosis were relatively resistant to PMP-induced killing. Compared with C. albicans, C. neoformans was relatively resistant to the fungicidal activity of PMP, with a mean survival among the isolates studied of 77.4% +/- 12.4% (n = 6). Against C. albicans, PMP-induced fungicidal activity was time dependent (range, 0 to 180 min), PMP concentration dependent (range, 10 to 150 U/ml), and inversely related to the fungal inoculum (range, 5 x 10(3) to 1 x 10(5) CFU/ml). Scanning electron microscopy of PMP exposed C. albicans and C. neoformans cells revealed extensive surface damage and collapse, suggesting that the site of PMP fungicidal action may directly or indirectly involve the fungal cell envelope. PMID- 8460924 TI - Relative efficacies of broad-spectrum cephalosporins for treatment of methicillin susceptible Staphylococcus aureus experimental infective endocarditis. AB - The effects of treatment with broad-spectrum parenterally administered cephalosporins and cefuroxime, cefazolin, or nafcillin were compared in an experimental model of Staphylococcus aureus infective endocarditis, and the results in vivo were compared with the activities of the study drugs in vitro. After 3 days of treatment, all antimicrobial agents tested were more effective than no treatment in reducing the number of surviving bacteria in cardiac valve vegetations. Nafcillin was the most effective agent studied and was significantly more active than was ceftizoxime, ceftriaxone, cefotaxime, cefoperazone, cefuroxime, or cefazolin (P < or = 0.05). Cefpirome and ceftazidime were the most effective broad-spectrum cephalosporins. The outcome of treatment with cefpirome or ceftazidime was similar to that of treatment with nafcillin and significantly better than that of treatment with ceftizoxime or cefotaxime (P < or = 0.05). Treatment outcome correlated closely with the MICs of the antimicrobial agents for the study strain with the exception of ceftazidime, which was significantly more active in vivo in comparison with other agents than predicted by its MIC (P < or = 0.0003). When ceftazidime was excluded as an outlier, treatment outcome correlated with the MICs of the remaining study drugs (Spearman's correlation coefficient, 0.95; P < or = 0.0004), as well as with the estimated percentage of time during which the concentration of total drug (correlation coefficient, 0.85; P < or = 0.007) or free drug (correlation coefficient, -0.90; P < or = 0.003) exceeded the MIC. A consideration of total or free drug concentrations in relation to MICs did not significantly improve the correlation with outcome observed with the MICs alone. PMID- 8460925 TI - In vitro activity and beta-lactamase stability of FK-037, a parenteral cephalosporin. AB - The in vitro activity of FK-037, 5-amino-2-[[(6R, 7R)-7-[[(Z)-2-(2-amino-4 thiazolyl)-2- methoxyimino) acetyl] amino]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-(2-hydroxyethyl)-1H-pyrazoli um hydroxide, inner salt, sulfate (1:1), a new parenteral cephem, was compared with those of cefepime, ceftazidime, imipenem, and ciprofloxacin. FK-037 inhibited methicillin-susceptible staphylocci at < or = 4 micrograms/ml. Of 98 isolates of homogenous methicillin-resistant Staphylococcus aureus, 55 (56.1%) were inhibited by 8 micrograms of FK-037 per ml, compared to 3.1% for cefepime. Imipenem was the most active beta-lactam tested against staphylococci. The MIC of FK-037 for 90% of the strains tested (MIC90) was 0.06 micrograms/ml for hemolytic streptococci, Streptococcus pneumoniae, viridans group streptococci, and Streptococcus bovis. The MIC90 for many of the members of the family Enterobacteriaceae was 1 microgram/ml, similar to that of cefepime and lower than those of ceftazidime and imipenem. The MIC90 for Klebsiella pneumoniae and Enterobacter cloacae was 8 micrograms/ml, similar to that for cefepime, but all isolates were inhibited by 2 micrograms of imipenem per ml. K. pneumoniae isolates with cefotaxime and ceftazidime MICs of > 32 micrograms/ml with Bush type 2b' beta-lactamases were inhibited by 4 micrograms of FK-037 per ml. E. cloacae, Citrobacter freundii, and S. aureus stably resistant to FK-037 could be selected by repeated transfer in the presence of FK-037. The FK-037 MIC90 for Pseudomonas aeruginosa was 4 microgram/ml, compared to 32 microgram/ml for cefepime and ceftazidime and 8 microgram/ml for imipenem. Xanthomonas maltophilia, Pseudomonas cepacia, Acinetobacter anitratus, and Bacteroides species were resistant to FK-037 (MIC, more than or equal 32 microgram/ml). MBCs were identical to or within twofold of the MICs except for a 32-fold greater MBC for P. aeruginosa. Inoculum size and acid environment did not lower the activity of FK-037. FK-037 was not appreciably hydrolyzed by Bush group 1, 2a, 2b, and 2e beta-lactamases but was hydrolyzed by 2b' and 2d enzymes at rates comparable to that of ceftazidime. Nonetheless, FK 037 inhibited bacteria possessing TEM-3, -5, and -7 and SHV -5 at less than or equal 8 microgram/ml. Overall, FK-037 has lower MICs against staphylococci and P. aeruginosa than the currently available iminomethoxy aminothiazolyl cephalosporins and has activity against members of the family Enterobacteriaceae comparable to that of cefepime. PMID- 8460926 TI - Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. AB - We have studied the antiproliferative effects of mevinolin (lovastatin), an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, on the protozoan parasite Trypanosoma (Schizotrypanum) cruzi and its ability to potentiate the action of specific ergosterol biosynthesis inhibitors, such as ketoconazole and terbinafine, both in vitro and in vivo. Against the epimastigote form in vitro, mevinolin produced a dose-dependent reduction of the growth rate up to 25 microM, but at 50 and 75 microM, complete growth arrest and cell lysis took place after 144 and 96 h, respectively. A systematic study of the effects of mevinolin combined with ketoconazole and terbinafine, which act at different points in the ergosterol biosynthesis pathway, on the proliferation of epimastigotes indicated a synergic action, as shown by concave isobolograms and fractional inhibitory concentration indexes ranging from 0.17 to 0.54. Analysis of the sterol composition and de novo sterol synthesis in control and treated cells by thin layer and gas-liquid chromatographies showed that the antiproliferative effects of the drug alone and in combination were correlated with the depletion of the endogenous ergosterol pool and particularly with a critical (exogenous) cholesterol/endogenous 4-desmethyl sterol ratio in the cells. When we studied the effects of mevinolin on the amastigote form proliferating inside Vero cells in vitro, only very modest effects on the parasites were observed up to 0.75 microM; above this concentration, significant deleterious effects on the host cells were found. However, when the same concentration of the drug was combined with ketoconazole, it was able to reduce by a factor of 10 the concentration of the azole required to eradicate the parasite (from 10 to 1 nM), again indicating a synergic action. On the other hand, a combination of mevinolin and terbinafine had only additive effects on amastigotes, but a ternary combination of mevinolin, ketoconazole, and terbinafine was again clearly synergistic. In vivo studies with a murine model of Chagas' disease showed that mevinolin can also potentiate the therapeutic effects of ketoconazole in this system; combined treatment with the two drugs at doses that alone offered only limited protection against the parasite was able to essentially eliminate circulating parasites and produce complete protection against death. These results confirm the synergic action against the proliferative stages of T. cruzi both in vitro and in vivo and in vivo of combined ergosterol biosynthesis inhibitors that act at different points in the pathway and suggest that mevinolin combined with azoles, such as ketoconazole, can be used in the treatment of human Chagas' disease. PMID- 8460927 TI - In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms. AB - The in vitro activity of RP59500, a streptogramin antibiotic, against 146 clinical isolates of vancomycin-resistant gram-positive bacteria was examined. Five strains of the species Enterococcus casseliflavus and Enterococcus gallinarum, for which the MIC of vancomycin was 8 micrograms/ml, were also studied. Twenty-eight vancomycin-susceptible strains of Enterococcus faecalis and Enterococcus faecium were included for comparison. The drug was highly active against Leuconostoc spp., Lactobacillus spp., and Pediococcus spp. (MICs, < or = 2 micrograms/ml). RP59500 was more active against vancomycin-susceptible strains of E. faecium than E. faecalis (MICs for 90% of the strains [MIC90s], 1.0 versus 32 micrograms/ml). Vancomycin-resistant strains of E. faecalis were as resistant to RP59500 as vancomycin-susceptible strains (MIC90, 32 micrograms/ml), but some vancomycin-resistant E. faecium strains were relatively more resistant to the new agent (MIC90, 16; MIC range, 0.5 to 32 micrograms/ml) than were vancomycin susceptible organisms of this species. PMID- 8460928 TI - Efficacy of ampicillin-sulbactam versus that of cefoxitin for treatment of Escherichia coli infections in a rat intra-abdominal abscess model. AB - We examined the efficacy of ampicillin-sulbactam (2:1) and cefoxitin in the treatment of infections caused by Escherichia coli strains exhibiting increasing levels of beta-lactamase-mediated resistance to ampicillin-sulbactam in the rat intra-abdominal abscess model. Cefoxitin was superior to ampicillin-sulbactam in the treatment of infections caused by all strains. Treatment with ampicillin sulbactam resulted in a statistically significant decrease in CFU per gram of abscess in comparison with treatment with ampicillin alone for both the moderately resistant and the resistant strains, with an inverse correlation between the MIC and the absolute decrease in CFU per gram of abscess. PMID- 8460929 TI - Reproducibility of the microdilution checkerboard method for antibiotic synergy. AB - We assessed the reproducibility of the microdilution checkerboard method for measuring antibiotic synergy. Five strains of Pseudomonas aeruginosa were tested with four antibiotic combinations by using 10 replicates each. Twenty-five percent of replicate sets gave discordant classification results (i.e., a 7:3 or worse split in categorization). Determination of the individual MICs of each antibiotic alone was excellent; all 10 replicates were within 1 twofold dilution for 95% of the 80 sets of 10 replicates. The microdilution checkerboard method either should not be used or should be used with at least five replicates per determination, with > or = 80% agreement among the replicates required for classification. PMID- 8460930 TI - Cefotaxime breakpoint for Streptococcus pneumoniae. PMID- 8460931 TI - Activity of several S-adenosylhomocysteine hydrolase inhibitors against African swine fever virus replication in Vero cells. AB - Several inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase have been found to selectively suppress the replication of African swine fever virus (ASFV) in Vero cells. Of the compounds tested, 3-deazaneplanocin A proved to be the most potent and selective inhibitor of ASFV replication. Its selectivity index (SI) was 3000. Then followed 9-(trans-2',trans-3'-dihydroxycyclopentyl)-3- deazaadenine (SI = 2500), the 4'beta-vinyl derivative of 9-(trans-2',trans-3' dihydroxycyclopentyl)adenine (SI = 2000), 6'beta-fluoroaristeromycin (SI = 1250), 4',5'-unsaturated 5'-fluoroadenosine (MDL 28842) and 9-(trans-2',trans-3' dihydroxycyclopentyl)adenine (SI = 667), 9-(trans-2',trans-3'-dihydroxycyclopent 4'-enyl)adenine and the 4 beta-methyl derivative of 9-(trans-2',trans-3'- dihydroxycyclopentyl)adenine (SI = 400), 9-(trans-2',trans-3'-dihydroxycyclopent 4'-enyl)-3-deazaadenine (SI = 200). We postulate that the mechanism of anti-ASFV action of these compounds is based on the inhibition of AdoHcy hydrolase, thus resulting in the accumulation of AdoHcy and suppression of methylation reactions needed for viral mRNA maturation. PMID- 8460932 TI - Characterization of murine Caraparu Bunyavirus liver infection and immunomodulator-mediated antiviral protection. AB - A rapid, peripheral disease model utilizing the Bunyavirus, Caraparu, was established in mice for the evaluation of antiviral therapy with immunomodulators. 4-6-week-old B6C3F1 female mice, inoculated intraperitoneally with virus, developed coagulative liver necrosis and died between 4-6 days after infection. This Caraparu disease model was relatively resistant to treatment with immunomodulators, such as ABMP, Ampligen, alpha-interferon (IFN-alpha) or beta interferon (IFN-beta). However, a significant increase in median survival time (MST) was consistently observed upon treatment with gamma-interferon (IFN-gamma). The nucleoside analog--ribavirin--was highly effective against Caraparu virus in repeated treatment schedules begun on either day -1, day 0, or day +1 of infection. Ribavirin gave little protection when initiation of treatment was delayed until day +2. However, combined treatment with IFN-gamma, starting on day 0 and ribavirin starting on day +2, significantly reduced mortality. PMID- 8460933 TI - The importance of light in the anti-HIV effect of hypericin. AB - The requirement for light in the anti-HIV-1 activity of hypericin was investigated. The hypericin concentration-dependence and light dosage-dependence of the reaction were measured. Under conditions in which hypericin caused substantial inactivation of HIV-1, there was a strict requirement for visible light. Only when the concentration of hypericin approached the cytotoxic level was there an apparent light-independent antiviral effect. This strict light requirement for the antiviral effect could explain some of the apparently discrepant results reported by other workers. Furthermore if hypericin is contemplated for use in humans, the importance of light must be considered. PMID- 8460934 TI - The physical basis of the genetic code: the choice between speed and precision. PMID- 8460935 TI - Differential prenylation of proteins as a function of mevalonate concentration in CHO cells. AB - The incorporation of [5-3H]mevalonate into prenylated proteins and polyisoprenoid lipids has been determined as a function of mevalonate concentration in Chinese hamster ovary (CHO) cells that are inhibited in mevalonate synthesis. The relative incorporation of mevalonate into the different end products of isoprenoid metabolism was markedly dependent upon the concentration of mevalonate in the medium. The synthesis of cholesterol was dominant at higher concentrations of mevalonate while higher molecular weight isoprenoids were favored at the lower concentrations. The relative incorporation of mevalonate into the different prenylcysteines of prenylated proteins was dependent upon mevalonate concentration with geranylgeranylcysteine being the principal product at higher concentrations. At low levels of mevalonate farnesylcysteine synthesis predominated and geranylcysteine was detected. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of proteins from CHO cells that had been radiolabeled at different concentrations of [3H]mevalonate had different patterns on fluorography with relatively few proteins labeled at low concentrations. A study of this effect on the prenylcysteines of a specific protein, Ras, showed considerably less sensitivity to mevalonate concentration than bulk protein. These results indicate that the specific proteins that are prenylated depend upon the availability of the isoprenyl diphosphate substrates. PMID- 8460936 TI - Regulation of hepatic lecithin: retinol acyltransferase activity by retinoic acid. AB - The activity of the hepatic enzyme lecithin: retinol acyltransferase (LRAT), thought to catalyze the esterification of retinol for storage, was previously shown to vary directly with the vitamin A (retinol) status of the rat [Randolph, R. K., and Ross, A. C. (1991) J. Biol. Chem. 266, 16453-16457]. The present studies were designed to determine whether liver LRAT activity is regulated in vivo by retinoic acid, a principal active metabolite of retinol. LRAT activity was negligible in the livers of vitamin A-deficient rats. Following treatment with a single 2-micrograms dose of retinoic acid, LRAT activity increased significantly while, following treatment with a single 20-micrograms dose, liver LRAT activity equalled that of vitamin A-sufficient adult rats. Retinoic acid was more effective than an equimolar quantity of retinol in restoring LRAT activity in the vitamin A-deficient rat liver. The increase in hepatic LRAT activity after administration of retinoic acid occurred rapidly, reaching a maximum within 12-16 h but declining again after 48-72 h. Studies were conducted in vivo to gain insight into the level of regulation of LRAT by retinoic acid. The increase in LRAT activity by retinoic acid in the vitamin A-deficient rat was blocked completely by both actinomycin D and cycloheximide. The ability of liver to esterify retinol in vivo was correlated with the in vitro activity of LRAT after retinoic acid induction. We conclude that retinoic acid, an important end product of retinol metabolism, regulates a key aspect of hepatic retinol metabolism through its regulatory activity on liver LRAT. PMID- 8460937 TI - Coordinate induction of the urea cycle enzymes by glucagon and dexamethasone is accomplished by three different mechanisms. AB - Induction of the mRNAs of the five urea cycle enzymes by glucagon and dexamethasone was studied in cultured rat hepatocytes to define mechanisms which coordinate the increases in the enzyme activities by these hormones. The transcription rate for arginase mRNA increased 9-fold in 7 h, the mRNA level 90 fold in 28 h, and the arginase activity 1.5-fold at 48 h, suggesting that induction is due primarily to stabilization of mRNA. Arginase mRNA induction was minimal with either hormone alone, combined hormones were synergistic, and cycloheximide pretreatment did not prevent the rise in mRNA levels. Carbamyl phosphate synthetase mRNA levels responded synergistically to the combined hormones and peaked 240-fold above controls at 24 h although activity only increased 1.4-fold at 48 h. Argininosuccinate lyase and synthetase mRNAs were induced by an increased transcriptional rate, were not induced by single hormones, responded synergistically to combined hormones, and showed a partial blockage of mRNA induction by cycloheximide. The ornithine transcarbamylase mRNA level was not increased by these hormones although activity increased 1.3-fold, suggesting stabilization of the enzyme. Thus glucagon and dexamethasone induce the urea cycle enzymes by three different mechanisms: transcriptional control of mRNA in argininosuccinate synthetase and lyase, stabilization of mRNA in carbamyl phosphate synthetase and arginase, and protein stabilization of ornithine transcarbamylase. PMID- 8460938 TI - Purification of multiple forms of cytochrome P450 from a human brain and reconstitution of catalytic activities. AB - The present study demonstrates the presence of multiple forms of cytochrome P450 (P450) in human brain obtained at autopsy, the purification of various isoforms to apparent homogeneity, and the monooxygenase activities in reconstituted systems. Sequential chromatography on octylamino-Sepharose 4B, DEAE-Sephacel, and DEAE-cellulose yielded four isoforms of P450 (A, B, C, and D) with specific contents of 11.0, 9.4, 12.5, and 8.3 nmol of P450/mg protein, respectively. While the forms A, B, and C were apparently homogeneous as examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; the P450D was not homogeneous. The apparent molecular masses of the four forms of P450 were 60,200 Da (P450A), 60,900 Da (P450B), 60,200 Da (P450C), and 61,000 Da (P450D), respectively. NADPH cytochrome P450 reductase (reductase) was also partially purified from the brain microsomes. Immunoblot analysis of the four forms of human purified P450, using antisera to purified rat liver P450 (IIB1 + IIB2), rat liver P450 (1A1 + 1A2), phenobarbital-inducible rat brain P450, human liver P450 IIE1, P450 1A2, P450 IIC, and P450 IIIA4, indicated differential immunological cross-reactivity. The monooxygenase activities of the purified human brain P450s were demonstrated with various substrates (aminopyrine, morphine, aniline, 7-ethoxycoumarin, and nifedipine) as examined in reconstituted systems consisting of purified human brain P450, purified rat brain NADPH cytochrome P450 reductase, deoxycholate, phospholipid, and NADPH. PMID- 8460939 TI - Characterization of rat plasma esterase ES-1A concerning its molecular and catalytic properties. AB - To characterize esterase ES-1A from rat plasma with regard to its molecular and catalytic properties, the enzyme was purified. The degree of purification, as measured by a densitometric gel scanning assay for ES-1 activity, was about 142 fold with a recovery of 9%. The ES-1A preparation was free of other plasma esterases but not of other plasma proteins. The enzyme shows microheterogeneity after staining for esterase activity in gradient polyacrylamide gel electrophoresis and isoelectric focusing. The native ES-1A protein is a carboxylesterase (EC 3.1.1.1) with a molecular mass of about 59 kDa as determined by gel filtration and gradient polyacrylamide gel electrophoresis. ES-1A exhibits a pI of 4.73 and optimum pH of 8.6 for p-nitrophenylbutyrate hydrolysis. With various p-nitrophenyl esters as substrate for ES-1A, it was found that the Michaelis constant decreased with increasing number of C atoms of the unbranched fatty acid moiety, whereas the maximum reaction velocity peaked with p nitrophenylvalerate. The high degree of similarity of the properties of rat ES-1A with those reported earlier for mouse ES-2B, rabbit EST-2F, and human ESB2 suggests that these four esterases have a common evolutionary origin. PMID- 8460940 TI - Secretion of platelet-activating factor acetylhydrolase following phorbol ester stimulated differentiation of HL-60 cells. AB - Platelet-activating factor (PAF) plays an important role in a number of biological processes ranging from inflammation to reproductive biology. We have reported that the enzyme that inactivates this potent autacoid, PAF acetylhydrolase (PAF-AH), is decreased in maternal plasma during the latter stages of pregnancy. This enzyme is associated with the plasma lipoprotein fraction and therefore its tissue origin was thought to be the liver. Prescott and colleagues (J. Biol. Chem. 265, 17381, 1990) have reported that both a rat liver cell line (HepG2 cells) and human peripheral macrophages secrete PAF-AH of the plasma type. We have shown previously that the injection of rats with dexamethasone or medroxyprogesterone causes an increase and estrogen a decrease in the plasma PAF-AH activity. To clarify the mechanism of hormonal regulation of PAF-AH production, we employed a monocyte-macrophage model system to investigate the secretion of PAF-AH during differentiation. In the present study, we have demonstrated that a myelocytic leukemic cell line (HL-60) produces and secretes PAF-AH into a defined medium when the cells are differentiated into macrophages following stimulation by 12-O-tetradecanoylphorbol-13-acetate (TPA). The medium obtained from unstimulated HL-60 cells did not contain detectable amounts of PAF AH activity. Stimulation with TPA caused a dose- and time-dependent increase in PAF-AH activity in the media. No increase in cell number was observed in the HL 60 cells during the culture period after the cells were treated with TPA. Cell lysis was excluded by the demonstration that the TPA-induced adherent cells excluded trypan blue and did not release lactate dehydrogenase activity into the medium. The increase in PAF-AH activity was inhibited by actinomycin D and cycloheximide. Dexamethasone and medroxyprogesterone markedly increased the secretion of PAF-AH by these cells, while estrogen was without effect. Bacterial endotoxin (lipopolysaccharide, LPS) inhibited the production of PAF-AH by these cells in a dose-dependent manner. The stimulation of PAF-AH secretion during differentiation of HL-60 cells and its modulation by LPS and steroid hormones may provide a useful model system for studying PAF metabolism during the inflammatory response and pregnancy. PMID- 8460941 TI - Time-dependent uncoupling between myosin phosphorylation and contractile force induced by Ca(2+)-depletion in smooth muscle. AB - Phosphorylation of the 20,000-Da myosin light chain is an important regulatory mechanism of smooth muscle contraction. In this study, we investigated the uncoupling between carbachol-activated myosin phosphorylation and isometric stress in Ca(2+)-depleted bovine tracheal smooth muscle at low [Ca2+]. In control tissues, lowering extracellular [CaCl2] from 1.6 to 0.1 mM had insignificant effects on carbachol-activated steady-state isometric stress and myosin phosphorylation. In contrast, in Ca(2+)-depleted tissues, lowering [CaCl2]0 from 1.6 to 0.1 mM significantly reduced steady-state isometric stress without significantly changing steady-state myosin phosphorylation, thus uncoupling contractile force from myosin phosphorylation. Time-course data of myosin phosphorylation and isometric stress revealed that isometric stress and myosin phosphorylation were coupled at the beginning of contractions, but then gradually became uncoupled at steady state. We attempted to stabilize the cell membrane and contractile filaments using high [Mg2+]. However, 25 mM [MgSO4] further reduced steady-state isometric stress development at 0.1 mM [CaCl2]0 without significantly changing steady-state myosin phosphorylation. These results indicated that Ca(2+)-depletion induced a time-dependent cellular process which gradually uncouples contractile force from myosin phosphorylation. Furthermore, steady-state isometric stress appeared to be not limited by myosin phosphorylation, but sensitive to the [Ca2+]/[Mg2+] ratio near the cell membrane. PMID- 8460942 TI - Further biochemical characterization of rabbit reticulocyte eIF-4B. AB - In this report, it is shown that eIF-4B exhibits ATP hydrolysis activity in a ribosome-dependent fashion. This activity is significantly enhanced by the addition of eIF-4A and eIF-4F, although neither of these factors, alone or together, display a significant ribosome-dependent ATPase activity. Sepharose-6B gel filtration experiments with combinations of nonlabeled and 14C reductively methylated initiation factors (eIF-4A, eIF-4B, eIF-4F, and eIF-3) provide evidence that both eIF-4B and eIF-4F, but not eIF-4A, interact with ribosomes in the presence of specific factors and ATP. It is not known with which ribosomal subunit(s) these factors interact. In ultraviolet radiation-induced crosslinking studies, an eIF-4A and/or eIF-4F and ATP-dependent crosslinking of eIF-4B to radiolabeled oligo(A)12-18 was observed. Past studies with oxidized-cap mRNA achieved cross-linking of all three of these factors, driven by the specific interaction of eIF-4F p24 with the m7GTP cap structure; this is the first reported instance of only eIF-4B cross-linking to RNA. PMID- 8460943 TI - Thermodynamic elucidation of structural stability of deuterated biological molecules: deuterated phospholipid vesicles in H2O. AB - Thermodynamic studies of deuterated phospholipids in H2O were conducted using deuterated lipid bilayer vesicles prepared from aqueous dispersions of 1,2 dimyristoyl-d54-, 1,2-dipalmitoyl-d62-, and 1,2-distearoyl-d70 phosphatidylcholines. The results obtained in combination with those previously reported in D2O made possible the evaluation of deuterium solvent and deuterium alkyl-chain substitution effects in deuterated phospholipids. These effects included the temperature (delta tm), the enthalpy (delta delta H), the free energy (delta delta G), the entropy (delta delta S), and the cooperative melting unit (delta n) of the main lipid phase transition from the gel to the liquid crystalline phase. To supplement thermodynamic observations, fluorescence steady state polarization measurements were also performed. The results were examined to elucidate the nature of interactions in deuterated compounds. The deuterium solvent effect increases the structural stability of deuterated lipid vesicles, due to an enhancement of hydrophobic interaction in D2O. This observation is contrary to that previously reported for deuterated proteins, phycocyanins, where structural stability is reduced in D2O solvent. These findings therefore support the proposal that an alteration in hydrophobic interactions in deuterated proteins due to deuterium substitution is not likely to play a significant role in contributing to the structural instability of proteins. PMID- 8460944 TI - Hydride shifts in the biosynthesis of the p-menthane monoterpenes alpha terpinene, gamma-terpinene, and beta-phellandrene. AB - The biosynthesis of several monoterpenes from the acyclic precursor geranyl pyrophosphate requires the migration of positive charge from the isopropyl side chain into the cyclohexenoid ring of the universal alpha-terpinyl cation intermediate of the reaction. The hydride shifts responsible for charge migration in the formation of three p-menthane olefin isomers were examined in a range of plant species: alpha-terpinene in American wormseed, gamma-terpinene in thyme, and (-)-beta-phellandrene in lodgepole pine. The experimental approach utilized soluble cell-free enzyme systems and specifically labeled geranyl substrates, with the determination of the labeling patterns in the resulting cyclic products. The results were consistent with stereoelectronic features of the cyclization and support the general model for monoterpene formation. PMID- 8460945 TI - Structures of mucin-type sugar chains on human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. AB - Less is known about the mucin-type sugar chains attached to human erythropoietin as compared with N-linked sugar chains which structures and function have been well studied. In this study, we purified urinary human erythropoietin from three independent groups of aplastic anemia patients, and analyzed the structures of mucin-type sugar chains as well as that obtained from recombinant human erythropoietin produced by Chinese hamster ovary cells. Unlike the N-linked sugar chains, the mucin-type sugar chains are totally different between the urinary and the recombinant erythropoietins. All of the three independent samples of urinary erythropoietin contained oligosaccharides with the structures of +/- Neu5Ac alpha 2-->6GalNAc, while recombinant human erythropoietin contained those with the structures of Neu5Ac alpha 2-->3Gal beta 1-->3(Neu5Ac alpha 2-->6)GalNAc, Neu5Ac alpha 2-->3Gal beta 1-->3GalNAc, and Gal beta 1-->3(Neu5Ac alpha 2-->6)GalNAc. PMID- 8460946 TI - Modulation of the fumarases of Escherichia coli in response to oxidative stress. AB - The [4Fe-4S]-containing fumarases A + B of Escherichia coli are susceptible to oxidative inactivation, while fumarase C, which is not an iron-sulfur protein, is induced under oxidative conditions. Thus, imposition of oxidative stress, whether by addition of paraquat or by mutational deletion of superoxide dismutases, diminished fumarases A + B while elevating fumarase C. H2O2 appeared to be one cause of the inactivation of fumarases A + B, but was not involved in the induction of fumarase C. Thus lack of hydroperoxidases I and II did increase the paraquat-elicited inactivation of fumarases A + B without affecting the induction of fumarase C by paraquat. The importance of Fe(II) for the unstable fumarases was exposed by alpha,alpha'-dipyridyl, which decreased fumarases A + B without affecting fumarase C or the inductive effect thereon of paraquat. The oxidative inactivation and the subsequent reactivation of fumarase A was examined in extracts. Under air there was a first-order inactivation of fumarase A, which was rapidly reversed when O2 was excluded. The role of iron loss and restitution, in this inactivation and reactivation, was clarified by EDTA, which was without effect on the aerobic inactivation, but blocked the anaerobic reactivation. These results are consistent with a predominantly ferric state of the available iron in the presence of O2 and of the ferrous state in the absence of O2. PMID- 8460947 TI - Redox potential and electrostatic effects in competitive inhibition of dual-path electron transfer reactions of spinach plastocyanin. AB - Redox inactive ions with high positive charges lower the rate constant for oxidation of several plant plastocyanins (PC) by small positively charged inorganic reaction partners. The rate constant decrease is commonly attributed to competitive inhibition where the redox inactive ions are bound to the negatively charged remote electron transfer (ET) site of PC and block this site sterically. We have investigated the effects of the inhibitor [NH3)5Co(NH2)Co(NH3)5]5+ on the ET reactions of spinach PC with [Co(phen)3]3+ (phen = 1,10-phenanthroline) and the electrically neutral analogue [Co(phen-SO3)3] (phen-SO3 = 5-sulfonato-1,10 phenanthroline) at the ionic strengths mu = 0.1 M and 0.03 M. Inhibition of the [Co(phen)3]3+ reactions is notably smaller for PC(II) reduction than for PC(I) oxidation. This is indicative of a redox potential increase of PC(II)/PC(I) on inhibitor attachment. The effect amounts to 16 mV at mu = 0.1 M and 31 mV at mu = 0.03 M. These data, and analysis in terms of ET theory show that inhibition cannot be caused solely by steric blocking. Driving force and interreactant electrostatic work terms are equally important. The PC(I)/[Co(phen-SO3)3] reaction exhibits a more entangled pattern. The rate constant first increases slightly with increasing inhibitor concentration, then drops, and approaches a constant value not far from the original value. This pattern is in line with association between the negatively charged -SO3- groups of the Co(III) complex and the inhibitor, and ET of the associate at both ET sites of PC. PMID- 8460948 TI - Oxidative modification of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides by an iron(II)-citrate complex. AB - Incubation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with Fe2+ and citrate results in rapid O2-dependent inactivation of the enzyme. Maximal rate of inactivation occurred at equimolar concentrations of Fe2+ and citrate. Loss of enzyme activity appears to be the result of selective oxidative modification, as evidenced by a corresponding increase in protein carbonyl content. Partially inactivated enzyme remained predominantly in the dimeric form with no change in the apparent affinity of the remaining active subunits for substrate. Modified Glu-6-PDH was, however, more susceptible to heat denaturation. Our results suggest that the Fe(2+)-citrate complex binds to the glucose 6-phosphate binding site and then undergoes reaction with H2O2 formed in solution leading to the oxidative modification of amino acids essential for enzyme activity. PMID- 8460949 TI - Purification and characterization of class mu glutathione S-transferase isozymes from rabbit hepatic tissue. AB - Class mu glutathione S-transferases (GSTs) are important in the detoxication of epoxides generated by oxidative metabolism. Phenobarbital, 3-methylcholanthrene, and pyridine have failed to enhance the expression of class mu GST isozymes in rabbit hepatic tissue (T. Primiano, S. G. Kim, and R. F. Novak, Toxicol. Appl. Pharmacol., 113, 64-73, 1992). Two class mu GST isozymes have been isolated from rabbit hepatic cytosol and purified to homogeneity using S-hexylglutathione agarose, CM-Sepharose, and PBE94 chromatofocusing chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses showed that both isozymes possessed M(r) values of approximately 25,500 and cross-reacted with class mu-specific GST IgG. Gel filtration analysis revealed that these isozymes were dimers with molecular weights of approximately 45 kDa. The class mu GST isozymes had pIs of 7.8 and 7.2 as determined by nonequilibrium pH gel electrophoresis. The class mu GST 7.8 and 7.2 isozymes exhibited different metabolic activities toward the substrates 1-chloro-2,4-dinitrobenzene, bromosulfophthalein, 1,2-epoxy-3-(p-nitrophenoxy)propane, trans-4-phenyl-3-buten 2-one, p-nitrobenzyl chloride, and 3,4-dichloronitrobenzene. Metabolic activity of the two GSTs toward the substrate 1-chloro-2,4-dinitrobenzene was inhibited by Cibacron blue, triethyltin bromide, S-hexylglutathione, bromosulfophthalein, and indomethacin. The amino acid composition of GST mu 7.8 and 7.2 was determined and found to be very similar to those of purified rat class mu GST isozymes. N terminal analysis of the first 21 residues of the pI 7.8 class mu GST isozyme revealed that it had 71 and 81% sequence identity with the Yb1 and Yb2 subunits, respectively. Similarly, N-terminal analysis of the first 21 residues of the pI 7.2 class mu GST isozyme revealed a 75% sequence identity with either the rat Yb1 or Yb2 subunit. Examination of class mu GST expression in rabbit hepatic cytosol following treatment with a series of known inducers including phenobarbital, 3 methylcholanthrene, isosafrole, pyrazine, trans-stilbene oxide, butylated hydroxyanisole, and tert-butylhydroquinone was accomplished. The data show that these agents not only failed to enhance class mu GST expression, but that 3 methylcholanthrene and isosafrole caused suppression of class mu GSTs. These results provide evidence for the existence of two closely related class mu GST isozymes in rabbit hepatic tissue and suggest that the molecular mechanisms regulating GST expression differ between rat and rabbit in response to these xenobiotics. PMID- 8460950 TI - Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. AB - In hepatocytes incubated in the presence of 20 mM glucose, strong stimulation of glycogen synthesis by LiCl was observed in cells from both normal and streptozotocin-induced diabetic rats. This stimulation was concentration- and time-dependent, and it was related to an increase in the glycogen synthase activity ratio. No effects of LiCl on glycogen phosphorylase activity were detected under these conditions. When hepatocytes were incubated with LiCl and insulin together, an additive effect on glycogen synthesis from glucose was observed. However, when hepatocytes were incubated in the presence of gluconeogenic precursors, such as lactate and pyruvate, and then with LiCl, no effect on glycogen accumulation was observed. Under these conditions, simultaneous activation of glycogen synthase and glycogen phosphorylase occurred. These results indicate that lithium ions, like insulin, are able to stimulate glycogen synthesis from glucose in diabetic rat hepatocytes, although the mechanisms of action of the two effectors on hepatic glycogen metabolism are probably different. PMID- 8460951 TI - Homoserine dehydrogenase-I (Escherichia coli): action of monovalent ions on catalysis and substrate association-dissociation. AB - Changes in the kinetic properties of homoserine dehydrogenase-I (HD-I) from Escherichia coli, caused by substitution of Na+ for the normal activating monovalent ion, K+, has been investigated by equilibrium isotope exchange kinetics (EIEK). HD-I, part of the aspartokinase/homoserine dehydrogenase-I complex, is one of the few dehydrogenases to exhibit allosteric feedback regulation and cation activation. EIEK methods are especially useful for definitively identifying which rate constants are altered by bound modifiers. Saturation curves for the [14C]Hse<-->ASA and [3H]NADP+<-->NADPH exchanges were compared in the presence of K+ vs Na+, varying different combinations of substrate pairs in constant ratio at equilibrium. Kinetic differences between the K+ and Na+ enzymes were analyzed systematically by simulations with the ISOBI program. This analysis clearly demonstrates that substituting Na+ for K+ shifts the kinetic mechanism from preferred order random to a nearly random order scheme, along with causing significant rate limitation at catalysis between the central complexes. Initial velocity kinetics demonstrate that HD-I has a 10-fold higher affinity for Na+ than K+, but that the Na(+)-enzyme is 10-fold less active and exhibits higher substrate Km values, especially for L-Hse. PMID- 8460952 TI - Subcellular localization of prostaglandin endoperoxide synthase-2 in murine 3T3 cells. AB - Polyclonal antisera specific for prostaglandin endoperoxide (PGH) synthases-1 and -2 were used to determine the subcellular locations of each PGH synthase isozyme in detergent-permeabilized mouse 3T3 fibroblasts by indirect immunocytofluorescence. Antiserum to PGH synthase-1 demonstrated a mottled pattern of cytoplasmic and perinuclear staining of both serum-starved and serum stimulated 3T3 cells. This pattern of staining is consistent with the results of earlier studies which demonstrated that PGH synthase-1 is associated with the endoplasmic reticulum and nuclear envelope of these cells. As expected, antibodies directed against a peptide unique to PGH synthase-2 failed to stain serum-starved cells, which lack appreciable levels of this second form of the enzyme. However, serum-stimulated 3T3 cells, which do express PGH synthase-2, showed the same pattern of staining with PGH synthase-2 antibodies as was observed with anti-PGH synthase-1 serum--mottled cytoplasmic staining and perinuclear staining. We conclude that the subcellular location of PGH synthase-2 is the same as PGH synthase-1 in murine 3T3 cells. Thus, the notable differences in the primary amino acid sequence--the signal peptide and the additional 18 amino acid C-terminal segment in PGH synthase-2--do not cause a change in localization. Colocalization of PGH synthases-1 and -2 implies that the source of arachidonate substrate, the site of PGH2 and prostanoid formation, and the mechanism of product transport from the inside to the outside of the cell are the same for these isozymes. PMID- 8460953 TI - Bias, ignorance, and gun control: a plea for education. PMID- 8460954 TI - A deceptive contrivance. PMID- 8460955 TI - Albendazole therapy for giant subarachnoid cysticerci. PMID- 8460956 TI - Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older. AB - Subjects with clinically diagnosed senile dementia of the Alzheimer type (n = 37) and healthy controls (n = 5) were assessed clinically until death. Postmortem examination of the brain was performed at age 80 years or older. The brains of all of the group with dementia (except one that was found to have a non-Alzheimer dementia) had substantial densities of neocortical senile plaques regardless of dementia severity; the control brains had very few senile plaques. In those subjects with Alzheimer's disease, moderate correlations were found between dementia duration and severity (cognitive portion of the Blessed Dementia Scale and the Sum of Boxes from the Clinical Dementia Rating) and certain neuropathological lesions, both gross and microscopic. Densities of neocortical neurofibrillary tangles were related to degree of dementia; densities of neocortical senile plaques were unrelated. We conclude that (1) neocortical senile plaque densities differentiate very old subjects with Alzheimer's disease from nondemented controls, but there is a need for more postmortem studies of older persons who are free of dementia; and (2) among the microscopic lesions studied, densities of neocortical neurofibrillary tangles were most closely related to the degree and duration of dementia. PMID- 8460957 TI - Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease. AB - OBJECTIVE: This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional, between-subject design, using an age-regression model. SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores. RESULTS: The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late onset group. This onset difference was also evident in neuropsychological test performance. CONCLUSIONS: This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes. PMID- 8460958 TI - Explicit memory in Alzheimer's, Huntington's, and Parkinson's diseases. AB - OBJECTIVE--Comparing the pattern of spared and impaired memory functions in neurodegenerative diseases known to affect different brain structures. DESIGN- Various situations of acquisition (free encoding or controlled encoding) and retrieval (immediate and delayed free and cued recall, recognition) were used. SETTING--Referral center. PATIENTS--Fifteen for each disease (ie, senile dementia of the Alzheimer type [SDAT], Parkinson's and Huntington's), matched for education, severity of dementia, and depression. MAIN OUTCOME MEASURES- Comparison of free and controlled encoding situations, relationships between memory, executive, and linguistic functions test scores. RESULTS--In the free encoding situation: no difference among the three groups, but higher numbers of intrusions and false recognitions in SDAT. In the controlled situation: cued recall and recognition scores significantly higher in Parkinson's disease and Huntington's disease than in SDAT. Memory performances correlated with executive functions test scores in Huntington's disease and Parkinson's disease, but not in SDAT. All results significant at P < .01. CONCLUSIONS--Clear distinction between the true amnesic syndrome of SDAT, compatible with lesions of hippocampus and temporal cortex, and the inefficient planning of memory processes of Huntington's disease and Parkinson's disease, which might result from a striatofrontal dysfunction. PMID- 8460959 TI - Influence of age on clinical and psychometric assessment of subjects with very mild or mild dementia of the Alzheimer type. AB - OBJECTIVE: The influence of age on performance on clinical and psychometric assessments is examined in groups of nondemented persons and individuals with either very mild or mild dementia of the Alzheimer type (DAT). DESIGN: Initial clinical and psychometric assessments of persons enrolled in longitudinal studies of DAT and nondemented control subjects. SETTING: Alzheimer's Disease Research Center at Washington University, St Louis, Mo. PARTICIPANTS: Volunteer samples of 108 people (44 men, 64 women) with mild DAT, 61 people (30 men, 31 women) with very mild DAT, and 122 healthy nondemented people (45 men, 77 women) were recruited between 1979 and 1991. Age ranged from 54 to 87 years. Persons with confounding medical, neurologic, or psychiatric disorders were excluded. Dementia severity was staged using the Clinical Dementia Rating scale. MAIN OUTCOME MEASURES: Five brief quantitative clinical tests included in the 90-minute clinician administered protocol, as well as 14 tests included in a 2-hour psychometric test battery. RESULTS: Dementia severity affected performance on all measurements. Age did not influence performance on clinical assessments. There was a significant interaction between age and dementia severity on 10 of 14 psychometric measures. In general, older nondemented individuals performed less well than younger nondemented individuals while older mildly demented persons performed about the same as, or slightly better than, their younger counterparts. CONCLUSIONS: Age does not affect performance on brief clinical assessment instruments. However, age affects psychometric performance differently in cognitively intact persons when compared with persons with DAT. As a result, psychometric differentiation between cognitively normal and demented individuals is more difficult in older populations. PMID- 8460960 TI - Altered brain energy metabolism in demented patients with multiple subcortical ischemic lesions. Working hypotheses. AB - We report the results of brain metabolic studies (using magnetic resonance spectroscopy) in three groups of individuals: (1) demented patients with multiple subcortical ischemic lesions (n = 18); (2) nondemented, age-matched controls (n = 21); and (3) demented patients with neurodegenerative disease, probably of the Alzheimer type (n = 19). Patients with dementia with subcortical vascular lesions, as demonstrated by appropriate imaging studies, had an increase of phosphate energy charge in areas of the cerebral cortex (especially prominent in the frontal regions) superficial to and excluded from the subcortical lesions. We hypothesize that this increased energy charge might be caused by reduced metabolic activity of disconnected brain tissue or by astrocytic hypertrophy and hyperplasia that accompanies subtle ischemic, cortical alterations. PMID- 8460961 TI - Hippocampal sclerosis and human memory. AB - OBJECTIVE: To study the effects of hippocampal sclerosis on preoperative neuropsychological memory tests. DESIGN: Analyses of variance and chi 2 tests were used to compare patient groups (divided retrospectively) with a control group. SETTING: Hospital epilepsy unit. PATIENTS AND OTHER PARTICIPANTS: All patients who underwent a temporal lobectomy for intractable seizure relief during the preceding 18 months were included if the following criteria were met: (1) age was between 15 and 55 years; (2) IQ was 80 or greater; (3) the left hemisphere was dominant for speech; (4) there had been no previous brain surgery; (5) sufficient hippocampal tissue had been supplied for pathologic study; and (6) there was no hippocampal abnormality other than sclerosis. The 40 patients who met all of these criteria were divided into groups based on pathological classification (presence or absence of hippocampal sclerosis) and side of excision. Ten normal control subjects, matched to the patients based on age and education, were also asked to perform the memory tests. All subjects approached gave their informed consent to participate in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: No group demonstrated impairments on measures of attention or recognition memory. A deficit in learning paired-word associates was found for the left hippocampal sclerosis, right hippocampal sclerosis, and left no-hippocampal sclerosis groups, but on tests requiring the delayed recall of information, only patients with hippocampal sclerosis were impaired. For verbal tasks, the delayed recall deficit was limited to patients with left-sided sclerosis. CONCLUSIONS: Hippocampal sclerosis impairs the ability to learn associations and to retain information over a delay interval. For the learning and retention of verbal material, the left hippocampus is more important than the right. PMID- 8460962 TI - Cranial magnetic resonance imaging in severe preeclampsia vs eclampsia. AB - OBJECTIVE: This study was undertaken to evaluate the hypothesis that severe preeclampsia and eclampsia are associated with unique cranial magnetic resonance images. DESIGN: Case series of women with severe preeclampsia and eclampsia. SETTING: Referral center. PATIENTS: Sixteen women with severe preeclampsia and 10 women with eclampsia. RESULTS: Half of the women with severe preeclampsia had abnormal scans with nonspecific foci of increased signal in the deep cerebral white matter on T2-weighted images. However, women with eclampsia had either a multifocal area of increased signal at the gray-white matter junction on T2 weighted images or cortical edema and hemorrhage. These findings are consistent with necropsy descriptions of cortical edema and petechial hemorrhage. Basal ganglion lesions were also common. CONCLUSIONS: These findings appear to be unique to eclamptic women and should be considered of diagnostic significance in contrast to the nonspecific changes in patients with severe preeclampsia. Cranial magnetic resonance imaging may, thus, be of value in cases with diagnostic uncertainty, atypical presentation, or focal neurologic deficit. PMID- 8460963 TI - Dyslexia, left-handedness, and immune disorders. AB - OBJECTIVE: To illuminate a possible three-way association between dyslexia, immune disorders, and left-handedness. Geschwind's, Behan's, and Galaburda's hypotheses have been of special interest in this connection. DESIGN: Statistical analysis based on general assessment of the prevalence of the three aforementioned conditions. PARTICIPANTS: There were 734 children included from a total of 1165 in grade 6 (about 12 years of age) in the municipality of Stavanger, Norway. SETTING: Educational and demographic statistics indicate that the municipality of Stavanger is representative of the national population at large regarding the three conditions examined. MAIN OUTCOME MEASURES: A screening test with high reliability and validity was used to assess reading ability. It measured word recognition and phonological decoding. The questionnaires that recorded the students' handedness and immune disorders were filled in by the parents. Handedness was assessed by a Norwegian version of the Oldfield Inventory. A questionnaire concerning allergies and asthma was used to assess the prevalence of immune disorders. RESULTS: The bivariate analyses disclosed a significant association between handedness and dyslexia and a significant but weak association between handedness and immune disorders. No significant association was found between dyslexia and immune disorders. A triadic analysis yielded the following: 66.7% of the left-handed dyslexic children had immune disorders (P > .05); 42.1% of the left-handed children with immune disorders had dyslexia (P < .01); and 32% of the dyslexic children with immune disorders were left-handed (P < .05). CONCLUSIONS: There seems to be some association between dyslexia, left-handedness, and immune disorders. Of the three factors, handedness seems to be the most important association. The findings lend some support to the one interpretation of the hypotheses of Geschwind, Behan, and Galaburda. PMID- 8460965 TI - Sympathetic skin response in patients with cerebellar degeneration. AB - Sudomotor function was studied based on sympathetic skin responses (SSRs) in 87 patients with various types of cerebellar degeneration. Evaluations of orthostatic hypotension and the R-R interval variation were also performed in these patients. The respective incidences of SSR abnormality and orthostatic hypotension were 44 (50.6%) of 87 and 39 (44.8%) of 87. Fourteen percent of the patients with abnormal SSRs did not have orthostatic hypotension, but 8% of the patients with normal SSRs did have orthostatic hypotension. Sympathetic skin responses were abnormal in most patients with Shy-Drager syndrome, sporadic olivopontocerebellar atrophy (OPCA), and striatonigral degeneration, whereas SSRs were normal in patients with familial OPCA, sporadic cerebellar atrophy, and familial cerebellar atrophy. We demonstrated that SSR can be used to evaluate sudomotor function in degenerative disorders of the central nervous system as well as in peripheral neuropathies. The vasomotor and sudomotor functions usually are both disturbed in patients with cerebellar degeneration, and the SSR can detect autonomic dysfunction as sensitively as does the head-up tilt test. We also concluded that sporadic OPCA differs from familial OPCA in that it has a much higher incidence of autonomic dysfunction and that degeneration of the cerebellar cortex did not affect the autonomic regulation. PMID- 8460964 TI - Immunoglobulin G immunosuppression of multiple sclerosis. Suppression of all three major lymphocyte subsets. AB - Six patients with relapsing chronic progressive multiple sclerosis were treated on 2 consecutive days with large amounts of IgG to induce immunosuppression. Peripheral blood lymphocyte subsets were monitored for 5 weeks after IgG treatment to determine immunosuppression. Decreased numbers of B, T, and natural killer lymphocytes were detected after treatment. Lymphocyte numbers were at a nadir 1 week after treatment, but an immunosuppressive effect continued to be present after 5 weeks. Although clinical efficacy was not evident in this brief open trial, the decrease of peripheral lymphocyte numbers and the apparent safety of the procedure warrant further study. PMID- 8460966 TI - Opportunistic cerebral vasculopathy and stroke in patients with the acquired immunodeficiency syndrome. AB - OBJECTIVE: To describe an unusual cause of stroke in patients with the acquired immunodeficiency syndrome. DESIGN: An observational case series of hospitalized patients with subsequent autopsy. MEASURES: Clinical, radiological, and pathological examinations were performed. RESULTS: In three of 14 patients with stroke, the infarctions were secondary to an opportunistic vasculopathy caused by Candida albicans, cytomegalovirus, or lymphoma. CONCLUSION: Opportunistic conditions may lead to vascular abnormalities and subsequent stroke in patients with the acquired immunodeficiency syndrome. PMID- 8460967 TI - Medical care and case fatality from myocardial infarction and coronary death in Newcastle and Perth. AB - Coronary mortality rates are significantly higher in Newcastle than Perth. In this paper we examine the extent to which this might be due to differences in medical treatment and case fatality. Population-based disease registers were used to identify all cases of non-fatal definite myocardial infarction (MI) and coronary death in people aged 25-64 years in the study populations between July 1988 and June 1990. Case fatality (at 28 days from onset of symptoms) was not significantly different between the centres. Thrombolytic therapy was used for one third of all hospitalised events in both centres. Other drugs of proven benefit were, however, used more often in Perth than in Newcastle. For example, during hospitalisation 74% of patients in Perth received beta-blockers compared with 41% in Newcastle (difference = 33%, 95% confidence interval (CI): 28%, 37%) and 85% of patients in Perth compared with 72% in Newcastle received aspirin (difference = 13%, 95% CI: 9%, 17%). Median lengths of stay in a coronary care unit (CCU) and total hospital stay were one day shorter in Perth. As case fatality was similar, the differences in mortality rates can be attributed mainly to differences in attack rates. Greater use of cardio-active drugs in Perth apparently did not result in improved short-term outcome although potential long term benefits cannot be judged yet. PMID- 8460968 TI - Clinical aspects of malignant mesothelioma in Australia. AB - Australia is currently experiencing an epidemic of malignant mesothelioma. The clinical aspects of malignant mesothelioma were investigated in 295 Australian patients as part of a national study of the disease. Most patients were male (91%), with the mean age at diagnosis being 64 years. The predominant cell type was epithelial (38%) and the majority of primary tumours arose from the pleura (94%). Mean survival was poor (17.6 months from first symptom; 11.8 months from diagnosis). Patients with a pleural primary tumour were more likely to present with dyspnoea, chest pain and cough; to have a pleural effusion diagnosed radiologically; and to have metastatic spread. Patients with a peritoneal primary tumour were more likely to present with weight loss, loss of appetite, abdominal pain and ascites; to have radiologic evidence of asbestos exposure; and to have spread along a needle track created during a diagnostic tap. A minority of patients had past thoracic conditions, or radiologic findings, specifically related to previous asbestos exposure. About one fifth of patients had no known asbestos exposure. Forty-one per cent of subjects received some form of chemotherapy, radiotherapy and/or surgery, but no formal disease staging had been documented for any patient. Proper controlled trials of secondary and tertiary treatments in malignant mesothelioma are now needed. PMID- 8460969 TI - Sheehan's syndrome: clinical profile, pituitary hormone responses and computed sellar tomography. AB - Twenty patients with the typical clinical presentation of Sheehan's syndrome were studied. All had a severe degree of hypopituitarism. The circulating mean basal levels of thyroid hormones, cortisol and prolactin were significantly lower (p < 0.05 to < 0.02) compared to those in 50 age matched controls. The provoked pituitary responses to combined pituitary stimulation in 13 patients were markedly lower (p < 0.02 to < 0.001) than those in ten age matched control subjects. Sellar computed tomography revealed an empty sella in all the patients; partial in five and complete in the remaining. A secondary empty sella is considered a characteristic finding in the classical form of Sheehan's syndrome. PMID- 8460970 TI - Ethics and clinical medicine. PMID- 8460971 TI - Continuous hepatic artery infusion of 5-fluorouracil for metastatic colorectal cancer localised to the liver. AB - Continuous regional delivery of chemotherapeutic agents offers the prospect of maximising dose intensity at the site of localised disease, while minimising systemic toxicity. This prospective phase II study evaluates the efficacy and toxicity of hepatic arterial infusion of 5-Fluorouracil (5-FU) via an implantable Infusaid pump in previously untreated patients with localised but unresectable hepatic metastases from colorectal cancer. In 25 patients the response rate was 56% and median survival was 15 months, comparable to previous reports utilising fluorodeoxyuridine (FUDR). Twenty per cent of patients (all responders) survived longer than three years. Systemic toxicity was trivial, and the practice of reducing the intensity of therapy when nausea or a rise in alkaline phosphatase occurred avoided the previously described local toxicity of biliary sclerosis seen frequently with FUDR. In selected patients, particularly those with more limited disease, this form of therapy is effective and well tolerated and warrants further evaluation as an alternative to FUDR. PMID- 8460972 TI - Autosomal dominant polycystic kidney disease (ADPKD)--mechanisms of cyst formation and renal failure. AB - None of the hypotheses proposed so far to explain cyst formation in autosomal dominant polycystic kidney disease (ADPKD) is entirely satisfactory, e.g. the theory of tubular obstruction by intraluminal polyps or dilatation of nephron segments as a consequence of abnormal compliance of the basement membrane. Recent in vitro studies show that (i) synthesis of basement membrane material is abnormal and that (ii) the direction of transepithelial resorptive flux into a secretory mode is reversed as a consequence of faulty insertion of Na, K-ATP'ase into the luminal membrane. It remains unclear why cystic transformation of a few percent of nephrons should cause endstage renal failure. Our clinical and experimental studies do not provide evidence to support some hypotheses proposed in the past, i.e. that renal parenchyma is compressed by expanding cysts and that glomeruli are overperfused. Our histological studies show that progression to endstage renal failure is associated with (i) progressive arteriolar lesions (out of proportion to the vascular lesions seen in extrarenal vascular beds; and (ii) progressive interstitial fibrosis. It appears that fibroblasts in ADPKD are particularly sensitive to platelet derived growth factor (PDGF) which is secreted by epithelial cells of the cyst wall in a paracrine fashion. In contrast to previous opinion, which was presumably skewed by ascertainment bias, it appears that not all, and perhaps not even a majority, of ADPKD patients progress to endstage renal failure. Factors related to progression are gender, family history and hypertension. Both abnormal sodium excretion and inappropriate renin secretion play a role in the genesis of hypertension. Elevated blood pressure, albeit within the normotensive range, is demonstrable even in prepubertal children. The involvement of renin in renal vasoconstriction of normotensive ADPKD patients suggests a particular role of ACE inhibitors in the management of these patients. PMID- 8460973 TI - The chronic B-cell leukaemias. PMID- 8460974 TI - Absence of amyloid deposition in gastroduodenal mucosa of uraemic patients undergoing dialysis treatment. PMID- 8460975 TI - Silent myocardial ischaemia is uncommon after uncomplicated acute myocardial infarction. PMID- 8460976 TI - Failure to detect measles virus sequences in lymphocytes of patients with multiple sclerosis. PMID- 8460977 TI - Caution in using wages to assess community savings. PMID- 8460978 TI - Tubulo-interstitial nephritis and uveitis (TINU) syndrome in an adult. PMID- 8460979 TI - The Arthur E. Mills oration--the right to live and the right to die. PMID- 8460980 TI - Culture-positive tuberculosis at St Vincent's Hospital, Melbourne, 1962-1989. AB - The disease type and demography of patients with culture confirmed tuberculosis (TB) diagnosed at St Vincent's Hospital, Melbourne between the years 1962 to 1989 were reviewed. Four hundred and eighty-two patients with culture-positive TB were identified whose origins were as follows: Australia 194; Northern Europe 38; The Mediterranean 98; Asia 60 and other or unknown 92. Patients whose country of birth was in Asia or the Mediterranean area accounted for 57% of patients in the 1980s; they presented at a younger age, with a higher proportion of extrapulmonary disease and a more equal sex distribution than did Australian born patients. The main types of extrapulmonary disease also differed for the various ethnic groups. The overall proportion of patients with an isolate resistant to at least one of the anti-TB drugs was 10.0% but in the Asian born was 21.7%. This survey, the longest series of bacteriologically confirmed cases of TB reported from a single institution in Australasia, has identified several changes in how TB is presenting for diagnosis. PMID- 8460981 TI - A survey of the efficacy of sustained-release monensin capsules in the control of bloat in dairy cattle. AB - Thirty-four farms in the Macalister Irrigation District in Gippsland, Victoria, using sustained-release monensin capsules in 5102 cattle in the 1990 bloat season were surveyed. Questions were asked about the prevention and incidence of bloat in 1989 and 1990. Eight farms not using the capsules were selected to act as controls. Relatively low rates of broken capsules (0.6%), injury to animals at administration (0.06%) and regurgitation (1.02%) were reported. A variety of preventive techniques were used. There was a significant decrease in the use of pasture spraying, drinking water administration and flank spraying of anti-bloat substances on the farms using the capsules in the 1990 season, with no compensatory rise in the use of other techniques. There was no significant change in bloat prevention techniques used on the control farms over the same period. Significantly fewer cattle on the farms using capsules were treated for, and fewer died of clinical bloat in 1990 than in 1989. There was no significant change in the incidence of bloat on the control farms over the same period. It was considered that the anti-bloat capsules were effective in reducing the incidence of clinical bloat in pasture-fed dairy cattle. PMID- 8460982 TI - Relationship between milk production and somatic cell count in dairy cows in East Gippsland. AB - The analysis of records for 75,821 herd tests on 23,700 cows in the Macalister Irrigation District of East Gippsland, using a model that also included stage of lactation, herd and cow effects, found a strong relationship between somatic cell count and milk production. Unit increases in the natural logarithm of the somatic cell count were associated with decreases in production of up to 2.6% in the range 54,598 to 403,429 cells per mL. This is equivalent to a decrease of 1.9% for a doubling of cell count from 100,000 to 200,000 cells per mL. Subclinical mastitis was assessed to be a significant source of loss in milk production in the study area. PMID- 8460983 TI - Experiences with a vaccine being developed for the control of swine dysentery. AB - A prototype vaccine that is being developed for the control of swine dysentery (SD) was tested in two groups of experimental pigs. Vaccination induced high circulating antibody titres against the aetiological agent, Serpulina (Treponema) hyodysenteriae. Pigs in the first trial were vaccinated twice before being challenged orally with the bacteria. Five of 6 unvaccinated animals developed dysentery within a fortnight of challenge, but only 1 of 6 vaccinated pigs showed signs of disease at this time. Unexpectedly, 1 mo after challenge, the surviving unvaccinated pig and 2 remaining healthy vaccinated animals succumbed to the disease. The reason for the development of this late-onset form of dysentery was not clear. In the second trial, 8 pigs were vaccinated 3 times. Only 2 of these animals (25%) developed severe dysentery after being mixed with infected pigs, whereas 7 of 8 (88%) unvaccinated control pigs in the same pen became diseased. The late-onset form of dysentery was not observed. The prototype vaccine for SD provided a useful level of protection, and could be used in programs to control the disease in Australia. PMID- 8460984 TI - A survey for mycoplasmas in bulk-tank milk of dairy herds in Western Australia. PMID- 8460985 TI - Detection of Libyostrongylus douglassi in ostriches in Australia. PMID- 8460986 TI - A case of giardiasis in a dog in Tasmania--a cause of disease or incidental finding? PMID- 8460987 TI - An attempt to prevent acute toxoplasmosis in macropods by vaccination with Hammondia hammondi. PMID- 8460988 TI - Assessment of tetracycline and Babesia culture supernatant as prophylactics for moderating reactions in cattle to live Babesia and Anaplasma vaccines. PMID- 8460989 TI - Strains of parasites. PMID- 8460990 TI - Pathology of experimentally-induced, acute toxoplasmosis in macropods. AB - Thirteen Tammar wallabies (Macropus eugenii) were dosed orally with 500, 1000 or 10,000 oocysts of Toxoplasma gondii, as part of a vaccination trial. Eleven animals died of acute toxoplasmosis 9 to 15 days after challenge. The lesions were similar in all animals, consisting of foci of necrosis and inflammation in the intestines, lymphoid tissue, adrenal cortex, heart, skeletal muscle and brain, and severe generalised pulmonary congestion and oedema. Free and intracellular tachyzoites of Toxoplasma were associated with the lesions. The remaining 2 animals had shown no signs of disease when euthanased four months after challenge. Small, focal, non-suppurative inflammatory lesions were seen in brain, heart and skeletal muscle of these animals and chronic Toxoplasma infection was confirmed by mouse inoculation. PMID- 8460991 TI - Benign footrot--an epidemiological investigation into the occurrence, effects on production, response to treatment and influence of environmental factors. AB - Benign footrot was studied in 1 1/2-years-old Merinos on 2 farms in central Victoria from September 1987 to August 1990, inclusive. Treatment groups of 100 sheep grazed together with the remaining untreated sheep. Inspections were carried out every 3 weeks during the spring transmission period until the number of lesions greater than score 2 dropped below 3%. At each inspection, each sheep was weighed and lesion scores for each foot and digit were recorded, the treated group of sheep was treated by standing in 20% (w/v) zinc sulphate-sodium lauryl sulphate for 1 hour, and bacteriological samples were randomly collected from 5 sheep with and 5 without lesions. Dichelobacter nodosus organisms were obtained from sheep in both groups. Laboratory tests indicated benign organisms in flock A and low virulence, intermediate organisms in flock B. During the first 2 years, the number and severity of lesions were greater in flock A than in flock B. However, in the third year, with an early 'autumn break', there was a rapid and severe outbreak of footrot in flock B; 98% of the flock had lesions at the first inspection in July 1989. Flock A had a less dramatic increase in lesions of footrot. Both treated and untreated groups in flock B recovered rapidly between the third and fourth inspections. A later increase in lesions for both flocks coincided with damage caused by barely grass seeds. During this period there was a significant difference (P < 0.001) in body weight between the treated and untreated sheep on farm B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460992 TI - The recombinant catalytic domain of human neutrophil collagenase lacks type I collagen substrate specificity. AB - The coding region for human neutrophil short form procollagenase lacking the hemopexin like domain coding region was amplified by polymerase chain reaction. Recombinant short form procollagenase was expressed in E. coli and purified in a three step procedure. Renaturation of this proenzyme was carried out by an effective new method using Q-Sepharose chromatography. Treatment of short form procollagenase with mercurials resulted in active short form collagenase M(r) 21,000 and an intermediate product of M(r) 23,000. These two products were separated by hydroxamate affinity chromatography. The active, short form collagenase M(r) 21,000 is stable. Despite full proteolytic activity, it lacks type I collagen substrate specificity and forms the basis for crystallisation experiments. PMID- 8460993 TI - Cloning and sequencing of a cDNA coding for bovine conglutinin. AB - A 912 bp bovine cDNA fragment encoding bovine conglutinin was amplified by the RT PCR technique. cDNA clones encoding the bovine conglutinin were isolated from a bovine liver cDNA library using a specific probe obtained from the PCR product. These cDNAs carry an insert of 1113 bp coding for a protein of 371 amino acid residues with a signal peptide of 20 residues. The deduced amino acid sequence of cDNA agrees with that determined by conventional amino acid sequence analysis. Two polyadenylation signal sequences were detected in the DNA sequence downstream of the 3' end of the gene. Southern blot analysis of total bovine genomic DNA indicated that there is only one copy of the gene encoding bovine conglutinin. Northern blot analysis of bovine tissues showed that conglutinin mRNA of about 1.5 kb is expressed in the liver and also slightly in the lung. PMID- 8460994 TI - ATP induces an intracellular calcium pulse in osteoclasts. AB - Adenosine triphosphate (ATP; 50 microM) induces a large, fast, transient increase in intracellular calcium ([Ca2+]i) in rabbit osteoclasts, as measured with fluo-3 on a confocal laser scanning system. The [Ca2+]i increase is most intense in the nuclei of these multinuclear cells, indicating that Ca2+ release is occurring just outside the nuclei. ATP produces a much larger effect than adenosine, indicating that these cells have P2 purinergic receptors. Ca(2+)-free bathing medium and the Ca2+ channel blocker Cd2+ both inhibit but do not block the effect, showing that internal Ca2+ release is involved, but that either the steady state Ca2+ influx or a change in influx is important in modulating the effect. Thapsigargin also inhibits the effect. The ATP effect is repeatable with no change in bathing medium, implying that this signalling pathway has a mechanism for adaptation to progressively higher levels of ATP. PMID- 8460995 TI - Structural studies on synthetic peptides from the principal neutralizing domain of HIV-1 gp120 that bind to CD4 and enhance HIV-1 infection. AB - In previous studies we have demonstrated that synthetic peptides, corresponding to sequences in the (307-330) region of the gp120 principal neutralizing domain of different HIV-1 isolates are specifically recognized by a site distinct from the high affinity gp120-binding site of CD4. Interestingly, a peptide designed from the HIV-1 MN strain is able to enhance viral infection, while a HTLV-IIIB derived analogue is at least ten-fold less efficient and no effect is shown by other tested peptides. This enhancing effect occurs in the early step of infection and it is not strain restricted. A correlation between structure and biological functions evidenced by CD, FT-IR, and preliminary mono and bidimensional NMR is presented in this paper. The experimental data are compared to the predictions obtained by theoretical calculations. PMID- 8460996 TI - Constitutive expression and production of tumor necrosis factor-beta in T-cell lines infected with HTLV-I and HTLV-II. AB - A highly sensitive enzyme-linked immunoassay was developed to detect soluble levels of TNF-beta. Analysis of TNF-beta in culture supernatants from long-term T cell lines infected with human T-cell lymphotropic virus (HTLV) types I and II demonstrated elevated levels of TNF-beta when compared with uninfected T-cell lines. Presence of interleukin-2 in the culture medium showed a synergistic effect upon TNF-beta production. Further, constitutive expression of TNF-beta mRNA was observed in most cell lines infected with HTLV-I or HTLV-II. These results demonstrate that infections with HTLV-I/II can alter production of TNF beta, presumably via the transactivation of TNF-beta promoter by the tax protein of HTLV-I and HTLV-II. PMID- 8460997 TI - Biphasic effect of extracellular ATP on the membrane potential of mouse thymocytes. AB - Extracellular ATP induced changes in the membrane potential of thymocytes from BALB/c mice were analyzed. At concentrations below 0.1 mM, ATP hyperpolarizes the cell membrane on the time scale of development of the Ca(2+)-signal. After a longer time hyperpolarization turns to depolarization. ATP concentrations higher than 0.5 mM caused rapid depolarization without previous hyperpolarization. Verapamil, quinine or the absence of extracellular Ca2+ blocked the hyperpolarization by ATP. In Na(+)-free medium the magnitude of depolarization decreased. Our data suggest a contribution of Ca(2+)-activated K+ channels to the hyperpolarizing effect of ATP at lower concentrations. The direction of membrane potential changes is determined presumably by a sensitive balance of ATP-receptor mediated Ca(2+)- and Na(+)-influx and the Ca(2+)-activated K(+)-channel activity. PMID- 8460998 TI - P2 purinergic agonists and 12-O-tetradecanoylphorbol-13-acetate, as well as protein kinase A activators, stimulate thyroglobulin secretion in FRTL-5 cells. AB - We studied the role of various intracellular pathways in thyroglobulin secretion. The P2 agonists (ATP, ADP, GTP), 12-O-tetradecanoylphorbol-13-acetate (TPA), and protein kinase A activators stimulate thyroglobulin secretion in cells grown without TSH. The effects of these agents are additive. Pertussis toxin partially inhibits the effect of ATP but has no effect on the action of GTP. ATP and GTP increase cytosolic calcium (279 +/- 16% and 302 +/- 22%, respectively) while TPA and TSH (1 mU/ml) do not. Thus, both the protein kinase A and kinase C pathways regulate thyroglobulin secretion in FRTL-5 cells. PMID- 8460999 TI - Secretory form of Alzheimer amyloid precursor protein 695 in human brain lacks beta/A4 amyloid immunoreactivity. AB - It is not clear how Alzheimer amyloid precursor proteins (APP) are metabolized in the brain itself. Secretory forms of APP in a phosphate buffer-soluble fraction were purified from post-mortem human brain by heparin-affinity and ion-exchange chromatography and analyzed by N-terminal amino acid sequencing and SDS polyacrylamide gel electrophoresis/immunoblotting. We found apparently similar multi-isoforms of secretory APP (at 93-97, 105-112 and 123 KDa) to those that we have described recently in cerebrospinal fluid. Antisera to the initial part of the beta/A4 sequence labelled only those bands that were found to react with antiserum to the Kunitz-type inhibitor insert of APP, suggesting that beta/A4 amyloid may be generated specifically from APP-695. PMID- 8461000 TI - Expression of GLUT4 glucose transporter mRNA and protein in skeletal muscle and adipose tissue from rats in late pregnancy. AB - We investigated the influence of pregnancy on the expression of insulin-regulated glucose transporter (GLUT4) mRNA and protein in skeletal muscle and adipose tissue. GLUT4 mRNA expression in quadriceps muscle from control and pregnant rats was similar in the fasted and fed states. When the level of expression was determined as the immunoreactive GLUT4 content per gram of tissue, the relative GLUT4 protein content of red quadriceps from pregnant rats was significantly higher than that for control rats in both the fed and fasted states. GLUT4 protein expression in white quadriceps from pregnant rats was significantly increased in the fed state compared to control rats, but there was no significant difference in the fasted state. In adipose tissue, the relative GLUT4 protein content was significantly lower in pregnant rats than control rats in the fasted state, but there was no significant decrease in the fed state. Although the expression of GLUT4 protein showed these variations in late pregnancy, there was no significant difference of GLUT4 mRNA expression between control and pregnant rats. These findings suggest that GLUT4 kinetics may differ between late pregnancy and the normal state, and these changes may be related to insulin resistance in pregnancy. PMID- 8461001 TI - Purification and characterization of reversible sperm motility inhibitors from porcine seminal plasma. AB - Two sperm motility inhibitors (SMI1 and SMI2) were purified from porcine seminal plasma with high performance liquid chromatography (HPLC). Their molecular weights are about 15,000 as estimated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Both of them decreased the percentage of motile spermatozoa in a dose dependent manner. The inhibitory effect can be abolished by addition of the porcine follicular fluid. Both SMI1 and SMI2 have similar amino acid composition, suggesting that they may be structurally related. They also have inhibitory effect on chymotrypsin. PMID- 8461003 TI - A novel method for glass micropipette polishing for electropatch clamp recording using oxygen plasma. AB - We have applied discharge plasma to the polishing of micropipettes for patch clamp experiments instead of the conventional heat-polishing method. Using the micropipettes given the treatment with O2 plasma, we succeeded in the formation of giga-seals on human Jurkat cells with 70% of trials. Ellipsometrical measurement of the effect of O2 plasma to etch thin films of SiO2 suggested that O2 plasma has virtually no effect on the etching of glass surface. Multiple advantages of this novel method for polishing are noted relative to the conventional method. In particular, this method makes the micropipette polishing remarkably convenient. The polishing effect of O2 plasma on micropipettes without effect on the physical etching provides a novel insight into the mechanism of polishing. PMID- 8461002 TI - Role of nitric oxide pathway in the protection against lethal endotoxemia afforded by low doses of lipopolysaccharide. AB - Survival after lipopolysaccharide challenge (LD80, 20 mg.kg-1, i.p.) was significantly enhanced by previous treatment with a microdose of LPS (50 micrograms.kg-1, i.v.). When NG-monomethyl-L-arginine, a specific inhibitor of the formation of nitric oxide from L-arginine, was given 30 minutes before microdose, survival was significantly reduced. When we monitored the serum Tumor Necrosis Factor (TNF) levels in both groups a significant reduction of TNF level after the microdose was observed in mice previously treated with L-NMMA. The ability of L-NNMA to reduce TNF release was dose dependent. PMID- 8461004 TI - Functionally distinct endothelin B receptors in vascular endothelium and smooth muscle. AB - IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1 (8-21)) (0.1 nM - 1 microM), a novel ETB selective endothelin (ET) agonist, produced endothelium-dependent relaxations in precontracted rabbit mesenteric artery (2 nM, EC50) and endothelium-independent contractions in porcine coronary artery (18 nM, EC50). ET-3 (0.1 nM-10 nM) produced qualitatively similar responses in the two tissues. The maximal contractions induced by IRL 1620 or ET-3 were substantially smaller (< 20%) than that produced by ET-1. BQ-123 (1 microM), an ETA receptor antagonist, inhibited responses to ET-1 without affecting IRL 1620- or ET-3-induced responses in either tissue. Thus functionally distinct ETB receptors mediating vasodilator and vasoconstrictor effects are located on the vascular endothelium and smooth muscle, respectively. The overall effect of ETB receptor activation on vascular tone is tissue-specific and presumably reflects differing receptor distribution at the two sites. PMID- 8461005 TI - Protein kinase C-alpha but not protein kinase C-epsilon is differentially down regulated by bryostatin 1 and tetradecanoyl phorbol 13-acetate in SH-SY5Y human neuroblastoma cells. AB - SH-SY5Y human neuroblastoma cells can be induced to differentiate by phorbol esters but not by bryostatins although both agents increase protein kinase C (PKC) activity in these cells to a similar extent. We examined whether this difference could be explained by differences in the responses of specific PKC isoenzymes. Both TPA and bryostatin 1 at 10 nM induced a rapid increase in membrane-associated PKC-alpha immunoreactivity which was sustained for 72 hours in TPA-treated cells, but was down-regulated within 24 hours in bryostatin treated cells. TPA likewise induced a sustained phosphorylation of an 80 kDa PKC substrate whereas in bryostatin-treated cells the 80 kDa substrate was rapidly phosphorylated reaching a maximum at 6 hours followed by a decline to basal level within 48 hours. A higher concentration of TPA (300 nM), which results in a less differentiated phenotype, induced down-regulation of PKC-alpha within 24 hours. In contrast, both TPA and bryostatin 1 stimulated translocation and a partial down-regulation of PKC-epsilon with similar kinetics. These results suggest that the divergent actions of bryostatin 1 and TPA in SH-SY5Y cells are at least partially due to differential modulation of PKC-alpha but not PKC-epsilon by these two agents. PMID- 8461006 TI - Estrogen stimulates the elaboration of cell/matrix surface-associated inhibitory factor of osteoclastic bone resorption from osteoblastic cells. AB - Osteoblast-like UMR106 cells secreted bone resorption-stimulating activity (BRSA) under stimulation by human parathyroid hormone 1-34. Most of BRSA was associated with cell/matrix surface and could be extracted by 2 M NaCl. Pretreatment with 17 beta-estradiol (E2) reduced BRSA by enhancing the elaboration of an inhibitory factor of BRSA in a dose-dependent manner, and 10(-9) M 17 beta-E2 showed a significant effect. Neither 17 alpha-E2 nor dihydrotestosterone showed a similar effect. The inhibitory factor of BRSA was also bound to cell/matrix surface, showed affinity for heparin, and was trypsin- and heat-sensitive. Furthermore, this factor could also inhibit resorption pit formation stimulated by 1,25 dihydroxyvitamin D3, interleukin (IL)-1 alpha and IL-6. Elaboration of such an inhibitory factor of bone resorption from osteoblasts may play an important role in the protective effect of estrogen against bone resorption. PMID- 8461007 TI - NO- and NO2-carrying molecules potentiate photorelaxation in rat trachea and aorta. AB - Photorelaxation elicited by ultraviolet light (366 nm) was investigated on isolated rat thoracic aorta and trachealis. Rat tracheal smooth muscle but not aorta did not show UV-induced photorelaxation. Both streptozotocin, NO-carrying molecule and N omega-nitro-L-arginine, NO2-carrying molecule significantly enhanced photorelaxation, concentration-dependently, in rat trachealis and aorta. Methylene blue (10 microM) inhibited the potentiation action of streptozotocin and N omega-nitro-L-arginine in both tissues. Superoxide dismutase (300 U/ml) enhanced streptozotocin- and N omega-nitro-L-arginine-potentiated photorelaxation in rat trachealis, while pyrogallol (0.1 mM), a potent O2- generating agent, inhibited streptozotocin-potentiated photorelaxation in trachealis. Streptozotocin was much more effective than N omega-nitro-L-Arginine in potentiating of photorelaxation elicited by UV light in both tissues. From these findings, we conclude that streptozotocin and N omega-nitro-L-arginine produce EDRF like labile substance(s) by UV irradiation. PMID- 8461008 TI - Interleukin 1 beta regulates glycogen metabolism in primary cultured rat hepatocytes. AB - We examined the effects of human recombinant IL-1 beta on glycogen metabolism in cultured rat hepatocytes. When IL-1 beta was present at 8 nM in the culture medium for 15 hours prior to cell harvest, glycogen storage in hepatocytes was lowered approximately by 60% of the control. The enzymatic activity of glycogen synthase I in the IL-1 beta-treated cells (8 nM) was decreased by 70%; however, the activity ratio of the synthases I to D was not different from the untreated. In addition, the activity of glycogen phosphorylase a, the active form of phosphorylase involved in glycogenolysis, was increased by approximately 27% while the total phosphorylase activity was not changed. The data demonstrate for the first time that IL-1 beta lowers the intracellular glycogen contents in primary cultured rat hepatocytes. PMID- 8461009 TI - Cloning and sequencing of cDNA encoding mouse GTP cyclohydrolase I. AB - A full-length cDNA clone for GTP cyclohydrolase I (EC 3.5.4.16) was isolated from a mouse brain cDNA library by plaque hybridization. The nucleotide sequence determination revealed that the length of the cDNA insert was 994 base pairs. The coding region encoded a protein of 241 amino acid residues with a calculated molecular mass of 27,014 daltons. The deduced amino acid sequence of mouse GTP cyclohydrolase I was found to be highly homologous to rat (96%) and human type 1 (89%) enzymes. PMID- 8461010 TI - Hepatocyte growth factor induces mitogenic reaction to the rabbit gastric epithelial cells in primary culture. AB - Hepatocyte Growth Factor (HGF) was originally identified as hepatotrophic factor for liver regeneration. More recently, HGF was revealed to stimulate proliferation of various epithelial cells. At present study, we have investigated the mitogenic effect of HGF on gastric epithelial cells in the primary culture system. HGF remarkably stimulated proliferation of these cells dose dependently and synergistically with EGF and insulin. Mitogenic action of HGF might be mediated not by intracellular Ca2+ but by tyrosine kinase pathway. Conditioned medium of cultured fibroblast-like cells showed proliferative effects on cultured gastric epithelial cells in a similar way as exogenous HGF. These results suggest that HGF might be involved in the repair process of gastric mucosa. PMID- 8461011 TI - Human monocyte chemotactic protein-3 (MCP-3): molecular cloning of the cDNA and comparison with other chemokines. AB - When human MG-63 osteosarcoma cells are triggered with IL-1 beta, they produce, among various other cytokines, also monocyte chemotactic proteins (MCPs). Homogeneous MCP-1, MCP-2 and MCP-3 were found to induce production of gelatinase B and chemotaxis of monocytes. Based on the almost complete amino acid sequence of natural MCP-3, two sets of degenerated oligonucleotides were used for the amplification of MCP-3 cDNA. Total RNA from stimulated MG-63 cells was reverse transcribed and PCRs done on the mRNA:cDNA duplex. Using the PCR-product, several cDNAs were isolated from a cDNA library of IL-1-stimulated MG-63 cells. From the cDNA sequence the complete primary structure of the protein was deduced: MCP-3 shows 71% and 58% amino acid homology with MCP-1 and MCP-2, respectively. Our study establishes MCP-3 as an inflammatory cytokine that regulates macrophage functions. Because MCP-3 is often produced by tumor cell lines and regulates protease secretion by macrophages, its production might also contribute to invasion and metastasis of cancer cells. PMID- 8461012 TI - Cytokinin-specific binding protein in etiolated mung bean seedlings. AB - We have found that a synthetic urea derivative, N-(2-chloro-4-pyridyl)-N' phenylurea (4PU30, forchlorfenuron), has even higher cytokinin activity than N6 benzyladenine (BA). Using [3H]4PU30 (2.83 TBq/mmol) as a probe, we confirmed chromatographically the presence of a high-affinity cytokinin-specific binding protein (CSBP) in whole-cell extract from etiolated mung bean seedlings. The apparent molecular weight of CSBP was estimated to be 21 kDa. The association constants (Ka's) of CSBP for 4PU30 and BA were calculated to be 4 x 10(10) M-1 and 3 x 10(9) M-1, respectively. Various active cytokinins showed mutually competitive binding to CSBP, and their affinities for CSBP corresponded well to their cytokinin activities at the tissue level. PMID- 8461014 TI - Impaired glycosylation of glycosylphosphatidylinositol-anchor synthesis in paroxysmal nocturnal hemoglobinuria leucocytes. AB - Metabolic labeling with [3H]sugars in vivo or [3H]sugar nucleotides in vitro of glycosylphosphatidylinositol (GPI)-anchor precursors in peripheral blood granulocytes and cultured T lymphocytes of paroxysmal nocturnal hemoglobinuria (PNH) patients showed a synthetic defect in the GPI-anchor. Among the GPI-anchor precursors, phosphatidylinositol (PI) was normally synthesized, while the synthesis of glucosaminylphosphatidylinositol (GlcN-PI) and subsequent mannosylation of GlcN-PI were inhibited in affected cells. The defect in the GPI anchor synthesis in PNH is thus attributed to interrupted glycosylation at plural sites in the synthesis of the common carbohydrate structure of the anchor. PMID- 8461013 TI - The Dictyostelium discoideum 5S rDNA is organized in the same transcriptional orientation as the other rDNAs. AB - In eukaryotes 5S rRNA genes are transcribed by RNA polymerase III. These genes occur in D. discoideum on the ca. 90 copies of an extrachromosomal palindrom together with the other ribosomal RNAs, which are generally transcribed by RNA polymerase I. A 5S rRNA gene has been isolated and its nucleotide sequence as well as the organization of the gene relative to the RNA polymerase I operon has been determined. The sequence of the coding region corresponds exactly to an earlier published 5S rRNA sequence. The genes are located just downstream from the 26S RNA and transcription orientations of the pol I genes and the pol III gene point into the same direction, away from the centromer of the palindrom. The isolated gene appears to be functional since it serves as a specific target for a nuclear protein, most likely TFIIIA. A genomic copy of a 5S rRNA pseudogene has been isolated from the D. discoideum strain V12. This pseudocopy contains nucleotides 52 to 82 of a bona fide 5S rRNA gene with only three mismatches. It resides 78 nucleotides downstream from the glu13(UUC) tRNA gene which in the D. discoideum strain V12 is associated with the retrotransposable element DRE. PMID- 8461015 TI - Separate regulation of heme oxygenase and heat shock protein 70 mRNA expression in the rat heart by hemodynamic stress. AB - To elucidate the role of heat shock proteins in hearts, we examined the expression of heme oxygenase (HO) and heat shock protein 70 (HSP70) mRNAs in hearts of rats subjected to hypoxia or pulmonary artery banding, both of which produce pressure overload to the right ventricle. At 3 d of hypoxia, HO mRNA levels were elevated about fourfold compared to the basal levels in both right and left ventricles, while HSP70 mRNA was not induced at all. Pulmonary artery banding markedly and immediately (within 6 h) increased HO mRNA levels in both ventricles, but induced HSP70 mRNA only in the right ventricle. This is the first in vivo evidence showing the separate regulation of HO and HSP70 gene expression in hearts by hemodynamic stress. PMID- 8461016 TI - Cytofluorimetric identification of two populations of double positive (CD4+,CD8+) T lymphocytes in human peripheral blood. AB - Two different subsets of CD4+,CD8+ T lymphocytes have been identified in peripheral blood collected from normal subjects and from patients with different diseases. The subpopulations differed in the degree of CD4 and CD8 antigen expression. Hence, it was possible to distinguish by cytofluorimetric analysis cells with a low (dim) or with a high (bright) fluorescence intensity after the staining with anti-CD4 or anti-CD8 mAbs. CD4+dim,CD8+bright lymphocytes were found in patients with EBV-infectious mononucleosis and were present for less than a month. CD4+bright,CD8+dim T cells were observed in neoplastic patients as well as in healthy subjects and were continuously present in similar percentages over a long period of time (at the moment, about 3 years). Both the subpopulations expressed CD2, CD3, CD5 antigens and had an alpha beta-TCR, but did not express CD1a or CD7. Only CD4+dim,CD8+bright cells expressed HLA-DR antigen and the activation marker CD38, while only CD4+bright,CD8+dim lymphocytes expressed CD56 and CD57 molecules. The hypothesis may be put forward that these two subsets represent an effort of the immune system to cope with different requirements, i.e., of viral or neoplastic origin, while it is not clear the meaning of these cells in healthy subjects. PMID- 8461017 TI - Lipoproteins upregulate high affinity Fc receptors in human monocytes. AB - Plasma lipoproteins have been implicated in immunoregulation. Here we report that LDL and VLDL up-regulate high affinity Fc receptors (Fc gamma RI) in normal human monocytes. Adherent monocytes were cultured for 4 days in media containing fetal calf serum or delipidated serum. Immunofluorescence analysis showed a significant decrease in percentage of Fc gamma RI-positive cells from 85 +/- 3 in medium containing normal serum to 54 +/- 9 in medium containing delipidated serum. The decrease in the fraction of cells expressing Fc gamma RI was parallel to a decrease in the average number of receptor molecules per cell as indicated by a decrease in the mean value fluorescence intensity from 234 +/- 20 to 112 +/- 14. The inhibition of Fc gamma RI expression was overcome by addition to the culture medium of LDL or VLDL. Since pure cholesterol is ineffective, it is proposed that these lipoproteins deliver a component(s) such as apolipoprotein B-100 which triggers a signal leading to up-regulation of Fc gamma RI in monocytes and macrophages. PMID- 8461018 TI - Expression of human endothelin receptor ETB by Escherichia coli transformants. AB - Membrane fractions from Escherichia coli transformed with an expression vector for the human endothelin receptor ETB were found to exhibit specific and saturable binding sites for labeled ET-1. Binding properties were similar to those observed in eukaryotic cells: KD was 110 pM and the three endothelin isoforms were equipotent in competition experiments. The importance of the cysteines located in each of the three extracellular loops was assessed by replacing them individually with alanine residues. Impaired binding was observed in each case but the effect was far more pronounced for the cysteine mutants of the first and second loop pointing to their critical importance for active ETB expression. PMID- 8461019 TI - Production and hydrolysis of cyclic ADP-ribose at the outer surface of human erythrocytes. AB - Hemoglobin-free membranes from human erythrocytes are able to convert beta-NAD+ to cyclic ADP-ribose, a calcium mobilizer as potent as inositol 1,4,5 trisphosphate. Identification of cyclic ADP-ribose was based on HPLC analyses and its Ca(2+)-mobilizing activity on sea urchin egg microsomes. Erythrocyte membranes also hydrolyze cyclic ADP-ribose to ADP-ribose. By comparing the cyclic ADP-ribose-synthesizing and -hydrolyzing activities on unsealed and right-side out resealed ghosts, it can be concluded that both are localized at the extracellular side of the membrane. This is confirmed by the demonstration of both enzyme activities on the surface of intact human red cells. Identification of the two enzymes involved in cyclic ADP-ribose metabolism might suggest some physiological role of this nucleotide in red cells. PMID- 8461020 TI - Arginine-vasopressin increases the release of ET-1 into perfusate of rat mesenteric artery. AB - The regulatory systems of endogenous endothelin-1 (ET-1) production from intact tissues and the effects of produced ET-1 on vascular tonus by a closed circuit perfusion system of rat mesenteric artery were investigated. It was demonstrated that ET-1 is released from intact mesenteric arterial beds from Wistar rats both under basal conditions and after stimulation with arginine-vasopressin (AVP) (10( 10)-10(-9) M). Furthermore, AVP (10(-10)-10(-9) M) markedly and dose-dependently induced the expression of prepro ET-1 mRNA in the mesenteric arterial beds. Increased release of ET-1 by AVP may contribute to maintaining vascular tonus. Concomitant addition of actinomycin D inhibited the increased expression of prepro ET-1 mRNA and reduced the amount of immunoreactive ET-1 found during the 6 hour perfusate from AVP (10(-10) M)-stimulated and -unstimulated tissues. PMID- 8461021 TI - Retinoic acid inhibits DNA and albumin synthesis stimulated by growth factor in adult rat hepatocytes in primary culture. AB - Retinoic acid inhibits proliferation as a result of inducing differentiation in various cells. Isolated hepatocytes have quiescent cell function and seldom proliferate in culture. It is of interest whether such function changes in proliferation induced by growth factors and the proliferation is inhibited by retinoic acid. In adult rat hepatocytes in primary culture, retinoic acid reduced DNA synthesis stimulated by epidermal growth factor or hepatocyte growth factor in a dose-related manner. Albumin synthesis was increased with EGF stimulation. Retinoic acid attenuated this increase, but affected neither albumin synthesis in the absence of EGF nor EGF binding to the cells. Adult rat hepatocytes in primary culture may proliferate with quiescent cell function. Retinoic acid inhibits such proliferation and cell function. PMID- 8461022 TI - Intronic androgen response elements of prostatic binding protein genes. AB - Transcription of the genes that code for the different components of Prostatic Binding Protein is dependent on androgens. DNA-cellulose competition assays have demonstrated the presence of regions with affinity for the androgen receptor located immediately upstream and in the first intron of these genes. DNase I footprinting in vitro now reveals the exact binding site of a receptor dimer in the first intron of the C3(1), C3(2) and C1 genes. Gene transfer experiments resulted in the description of functional androgen response elements in the C3 genes. The C1 intronic binding site, however, has a much weaker affinity for the DNA-binding domain of the androgen receptor, a characteristic that might explain its inability to function as an androgen response element in chimeric gene constructs. PMID- 8461023 TI - Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome. AB - We found 3 novel missense variants in the open reading frame of the prion protein (PrP) gene. The codon 105 point mutation (proline to leucine) was found on a codon 129 (Valine) PrP allele in 4 patients from 3 different Japanese families with Gerstmann-Straussler syndrome. The codon 180 variant PrP (valine to isoleucine) was found in Creutzfeldt-Jakob disease (CJD) patients with a similar clinical course to that of codon 178 mutation. The codon 232 variant PrP (methionine to arginine) was documented in the CJD patients with typical clinical and pathological findings. These variant PrP molecules were not detected in 200 normal Japanese PrP alleles. PrP has a large repertoire of variant forms, and each primary structure of PrP corresponds to the distinct phenotype of prion diseases. PMID- 8461024 TI - Fluoride causes suppression of neurite outgrowth in human neuroblastoma via an influx of extracellular calcium. AB - We have used human neuroblastoma NB-OK1 cells to investigate the regulatory mechanism of neurite outgrowth. Sodium fluoride suppressed forskolin-stimulated neurite outgrowth in a dose-dependent manner. Sodium fluoride increased intracellular free calcium concentrations ([Ca2+]i), but had no effect on the cAMP level, arachidonic acid (AA) release or phosphoinositide (PI) hydrolysis in NB-OK1 cells. The calcium response of sodium fluoride was dependent on the extracellular Ca2+. The dose-response curve for stimulation of [Ca2+]i elicited by sodium fluoride was similar to that for suppression of neurite outgrowth. The suppressive effect of sodium fluoride on neurite outgrowth was inhibited by nonspecific Ca2+ entry blocker Mn2+ but not by L-, N- and T-type Ca2+ channel blockers. Hence we describe for the first time a possible role for calcium signaling in the regulation of neurite outgrowth by a G protein activator in the human neuron-derived cell line. PMID- 8461025 TI - Application of chemical cytochrome P-450 model systems to studies on drug metabolism. VI. N,N-coupling reaction of N-methylaniline catalyzed by polypeptide bound porphyrinatoiron(III) and cytochrome P-450. AB - Polypeptide-bound porphyrinatoiron(III) effectively catalyzed the N,N-coupling reaction of N-methylaniline in the presence of NaBH4/O2/tetramethyl-ammonium hydroxide or cumenehydroperoxide, whereas the corresponding non-bound monomer porphyrinatoiron(III) had little catalytic activity. Rat liver microsomes also catalyzed the N,N-coupling which was inhibited by cytochrome P-450 specific inhibitors, SKF-525A and metyrapone. The polypeptide-bound porphinatoiron(III) appears to be an excellent cytochrome P-450 model for drug metabolism studies. PMID- 8461026 TI - Breeding experiments to combine the X-linked sparse-fur (spf) mutation with the autosomal recessive BALB/cByJ strain: testing the biochemical phenotype of double mutant mice as a model for ammonia: fatty acyl CoA synergism. AB - Breeding experiments were conducted to combine the X-linked sparse-fur (spf) mutation with ornithine transcarbamylase deficiency and the autosomal recessive deficiency of short-chain acyl CoA dehydrogenase (SCAD) in BALB/cByJ mice. We obtained spf/Y (scad/scad), spf/+ (scad/scad) and spf/spf (scad/scad) double mutants amongst the F2 progeny, which were tested and separated on the basis of urinary orotate and the GC/MS analysis of urinary butyrylglycine, methylsuccinate and ethylmalonate. The testing of the biochemical type was feasible both on the basis of a 24-h urine collection form adult mice kept in metabolic cages and on the basis of urine spots collected on filter paper from younger progeny. It is postulated that the spf/Y (scad/scad) double-mutant may serve as a useful animal model to study the ammonia: fatty acyl CoA synergism. PMID- 8461027 TI - Characterization of DNA binding properties of Yp20: an abundant nuclear protein isolated from Saccharomyces cerevisiae. AB - The aim of this study was to elucidate the function of Yp20 (yeast 20 kDa protein) which is an abundant basic DNA-binding protein copurified with yeast chromatin. The work presented here shows that Yp20 is a sequence specific DNA binding protein. DNA binding activity was extremely thermostable. The affinity of binding to TRP1 was higher than the affinity of binding to the B domain of ARS1. The dissociation half time of Yp20-DNA complexes was less than 1 min. Yp20 showed no homology to a similar abundant 21 kDa ARS binding factor II (ABFII), previously described. Competitive gel retardation assays revealed two different regions that were protected by Yp20. One was overlapping the ABF1 binding site on ARS1 and another protected region was found upstream to the translational start codon of the TRP1 gene. It thus appears that Yp20 may have a role in DNA replication and/or transcription. PMID- 8461028 TI - Taurine prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells. AB - Hyperglycemia is directly involved in the development of diabetic nephropathy. A high glucose concentration promotes membrane lipid peroxidation and stimulates collagen production in a variety of cultured cells. Taurine, a sulfur amino acid, is an endogenous antioxidant and antifibrotic agent. We tested whether taurine ameliorates the above effects of elevated ambient glucose on renal cells in vitro. Raising glucose concentration from 5.6 to 33.3 mM enhanced lipid peroxidation in rat mesangial cells, as assessed by malondialdehyde and conjugated diene content, and increased collagen production by 59%. Taurine prevented both glucose-induced effects in mesangial cells. In contrast, neither high glucose nor taurine, alone or in combination, affected lipid peroxidation or collagen production in MDCK or LLC-PK1 cells, derived from renal tubular epithelium. These results indicate that taurine may be a useful therapeutic agent to attenuate diabetic glomerulosclerosis. PMID- 8461029 TI - Characterization of recombinant human serotonin 5HT1A receptors expressed in Chinese hamster ovary cells. [3H]spiperone discriminates between the G-protein coupled and -uncoupled forms. AB - 5HT1A serotonin (5-hydroxytryptamine) receptors have been characterized by ligand binding in a recombinant Chinese Hamster Ovary cell line expressing the human receptor gene. The agonist ligand [3H]2-(N,N-dipropylamino)-8-hydroxy-1,2,3,4 tetrahydronaphthalene ([3H]8-OH-DPAT) and the antagonist [3H]spiperone were used. For both radioligands the binding sites labelled have the properties of 5HT1A receptors and most antagonists show roughly equal affinities for the receptors labelled by either [3H]8-OH-DPAT or [3H]spiperone. Agonists, however, show higher affinities for the sites labelled by [3H]8-OH-DPAT and the antagonist spiperone conversely shows a higher affinity for the sites labelled by [3H]spiperone. Whereas [3H]8-OH-DPAT binding is inhibited by guanosine triphosphate (GTP) the binding of [3H]spiperone is increased by GTP. A model is proposed for the results whereby [3H]8-OH-DPAT labels a form of the receptor coupled to a G-protein and [3H]spiperone labels a form of the receptor uncoupled from G-proteins (or possibly coupled to a different G-protein). PMID- 8461030 TI - Protection of erythrocytes against hemolytic agents by cyclodextrin polysulfate. AB - Cyclodextrins generally exhibit hemolytic activity, some at concentrations as low as 1-10 mg/mL or lower. However, we found previously that a highly polysulfated cyclodextrin has no demonstrable hemolytic activity (Macarak et al., Biochem Pharmacol 42: 1502-1503, 1991). In the present study, we determined that, in fact, cyclodextrin polysulfate (CDS) actively protected erythrocytes against hemolysis induced by a wide spectrum of hemolytically active substances, ranging from pharmaceuticals, such as chlorpromazine, to solid suspensions of siliceous particles. The protective action was also effective against the hemolytic action of non-sulfated cyclodextrins. The similar kinetic responses of the erythrocytes to CDS protection against such chemically and structurally diverse hemolytic agents suggest a common mechanism involving the cell. Addition of the sulfated cyclodextrins to other cyclodextrin compounds used to solubilize poorly soluble pharmaceutical agents can extend the allowable maximum dosage without deleterious hemolytic action. PMID- 8461031 TI - Binding of suprofen to human serum albumin. Role of the suprofen carboxyl group. AB - The binding of suprofen (SP), a non-steroidal anti-inflammatory drug of the arylpropionic acid class, and its methyl ester derivative (SPM) to human serum albumin (HSA) was studied by dialysis and spectroscopic techniques. In spite of the remarkable differences in the physicochemical properties of SP and SPM, the binding of each molecule to HSA was quantitatively very similar. Thermodynamic analysis suggests that the interaction of SP with HSA may be caused by electrostatic as well as hydrophobic forces, whereas the interactions with SPM may be explained by hydrophobic and van der Waals forces. Similarities in the difference UV absorption spectra between ligand-detergent micelle and -HSA systems indicate that the SP and SPM molecules are inserted into a hydrophobic crevice on HSA. The same studies suggest that the carboxyl group of SP interacts with a cationic sub-site which is closely associated with the SP binding site. Proton relaxation rate measurements indicate that the thiophen ring and propanoate portion of the SP molecule is the major binding site for HSA. The locations of SP and SPM binding sites were identified by using fluorescence probes which bind to a known site on HSA. The displacement data implied that SP primarily binds to Site II, while the high affinity site of SPM as well as low affinity site of SP are at the warfarin binding site in the Site I area. From binding data with chemically modified HSA derivatives, it is likely that highly reactive tyrosine (Tyr) and lysine (Lys) residues, which may be Tyr-411 and Lys 195, are specifically involved in SP binding. In contrast, these two residues are clearly separated from the SPM binding site. The binding of SP and SPM is independent of conformational changes on HSA that accompany N-B transition. There is evidence that the carboxyl group may play a crucial role in the high affinity binding processes of SP to HSA. PMID- 8461032 TI - Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro. AB - The fate of the toxic metabolite of dapsone, dapsone hydroxylamine, has been studied in the human red cell. Twice-washed red cells were incubated at 37 degrees with dapsone hydroxylamine: at 3 and 5 min, 27.0 +/- 2.2 and 33.2 +/- 2.7% of the haemoglobin had been converted to methaemoglobin, leading to a maximum at 45 min (45 +/- 1.8%). HPLC analysis revealed that parent amine was produced from dapsone hydroxylamine during methaemoglobin formation in the red cells. At 3 min, conversion of dapsone hydroxylamine to dapsone reached 7.0 +/- 3.9% leading to a maximum at 30 min (18.1 +/- 3.7%). There was a linear relationship between hydroxylamine-dependent methaemoglobin formation and conversion of hydroxylamine to dapsone (r = 0.97). At 4 degrees, methaemoglobin and dapsone formation was greatly retarded, and did not exceed 10%. Co-incubation of diethyl dithiocarbamate (DDC) with dapsone hydroxylamine and red cells led to a marked increase in methaemoglobin formation (61.4 +/- 3.4%) compared with hydroxylamine and red cells alone (45.0 +/- 1.8%, P < 0.001) at 45 min, and conversion of dapsone hydroxylamine to dapsone was almost doubled at 45 min (35.7 +/- 5.3%) compared with hydroxylamine and red cells (18.1 +/- 2.5%). A linear relationship between methaemoglobin formation and dapsone formation (r = 0.96) was also shown to occur in the presence of DDC. Incubation of red cells with DDC and dapsone hydroxylamine caused a significantly greater reduction in glutathione levels (98.3 +/- 1.6%) compared with red cells and dapsone hydroxylamine alone (84.8 +/- 2.7%) at 5 min (P < 0.001), although there was no significant difference between the groups at 15 min (96.9 +/- 2.6 vs 98.1 +/- 2.2%). Intra erythrocytic glutathione was then depleted by 75 +/- 3.4%, by pretreatment with diethyl maleate (6 mM), and these cells in the presence of the hydroxylamine showed a significant fall in both methaemoglobin generation (29.7 +/- 1.2 vs 35.0 +/- 1.7%) and parent amine formation (11.1 +/- 0.2 vs 16.5 +/- 1.1%) compared with untreated red cells at 45 min. It is possible that a cycle exists between hepatic oxidation of dapsone to its hydroxylamine and reduction to the amine within the red cell, which may lead to re-oxidation by hepatic cytochrome P450. This process may contribute to the persistence of the drug in vivo. PMID- 8461033 TI - Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes. AB - Coumarin is 7-hydroxylated by the P450 isoform Cyp2a-5 in mice and CYP2A6 in humans. Various drugs, endogenous substances, plant substances and carcinogens, altogether about 90 chemicals, were evaluated as possible inhibitors of coumarin 7-hydroxylase (COH) activity in mouse microsomes. The effects of selected compounds on COH activity in human liver microsomes were also tested. The furanocoumarin derivatives methoxsalen (8-methoxypsoralen) and psoralen proved to be the most potent inhibitors of mouse COH activity (IC50 values 1.0 and 3.1 microM, respectively). The furanocoumarins bergapten (5-methoxypsoralen), isopimpinellin (5,8-dimethoxypsoralen), imperatorin and sphondin also effectively inhibited mouse COH activity (IC50 values 19-40 microM). Methoxsalen, isopimpinellin and metyrapone were also inhibitors in mice in vivo. Methoxsalen was a potent inhibitor of COH activity also in human liver microsomes, (IC50 value 5.4 microM), whereas bergapten, isopimpinellin and imperatorin had no effect. The imidazole antimycotic miconazole was a potent but non-specific inhibitor of COH activity. Several known substrates and inhibitors of members in the CYP1A, CYP2B, CYP2C, CYP2D and CYP3A subfamilies were poor inhibitors of COH activity. These results suggest that (i) the coumarin-type compounds in particular interact with the active sites of Cyp2a-5 and CYP2A6, and (ii) the active sites of Cyp2a-5 and CYP2A6 are structurally different, since a number of compounds inhibited mouse, but not human COH activity. PMID- 8461034 TI - Studies on the reactivity of acyl glucuronides--IV. Covalent binding of diflunisal to tissues of the rat. AB - Acyl glucuronides have been shown to be reactive electrophilic metabolites capable of undergoing hydrolysis, rearrangement (isomerization via acyl migration) and covalent binding reactions to plasma protein. The present study was undertaken to explore the occurrence and extent of in vivo formation of covalent adducts of diflunisal (DF), a salicylate derivative which forms a reactive acyl glucuronide, with tissues and plasma protein of rats. Groups of rats were given 50 mg DF/kg i.v. twice daily for periods of up to 7 days. Steady state plasma concentrations of reversibly bound DF and its conjugates (as measured 6 hr after a dose) were achieved by the third day of dosing. T 1/2 values after cessation of dosing were about 5-10 hr. By contrast, covalent DF tissue adducts steadily accumulated over the 7-day dosing period. Maximum concentrations, measured 6 hr after the last dose, were 4.8 (liver), 1.0 (kidney), 0.74 (plasma), 0.26 (small intestine minus contents), 0.27 (large intestine minus contents) and 0.20 (skeletal muscle) microgram DF/g tissue or/mL plasma. T 1/2 values of about 50, 67, 18, 38 and 43 hr were obtained for liver, kidney, plasma and small and large intestine (respectively) after cessation of dosing. Thus, the study of acyl glucuronide reactivity and the question of any derived toxicity or immune responses should consider the formation of long-lived adducts in tissues as well as in plasma. PMID- 8461035 TI - Inhibitory action of chloramine on formate-metabolizing system. Studies suggested by an unusual case record. AB - We previously reported on a patient exposed simultaneously to methyl chloride and chloramine gas who developed metabolic acidosis and permanent blindness [M. Minami et al., Hum Exp Toxicol 11: 27-34, 1992]. The case report suggested the possibility of potentiation of methyl chloride toxicity by chloramine. The potentiating mechanism was investigated by exposing mice to methyl chloride followed by ammonia chloramine, and then the level of formate in urine samples was measured with an enzyme coupling method to detect disturbance of formate metabolism. Mice dosed with 0.05 mL 1.0 mM chloramine after methyl chloride exposure excreted a significantly larger amount of urinary formate than mice treated with only methyl chloride. There was no difference in urinary formate levels between mice treated with only 0.05 mL 1.0 mM chloramine and those given only the vehicle (0.1 M phosphate buffer pH 6.0) for chloramine. The underlying biochemical mechanism of deterioration of formate metabolism was found to be the inhibition of the enzyme, N10-formyl tetrahydrofolate (N10-f-THF) dehydrogenase by 0.56-3.35 microM chloramine in the in vitro experiment using the purified enzyme. Positive control mice, given orally 0.1 mL 10% methanol in 0.1 M phosphate buffer (pH 6.0) excreted the same amount of urinary formate as those receiving 0.05 mL 1.0 mM chloramine after methanol administration. This was ascribed to the inhibitory effect of chloramine on formaldehyde dehydrogenase and depletion of substrate for further metabolism. The inhibition of the enzyme by chloramine (2.7-100.8 microM) was confirmed by in vitro experiments, using the purified enzyme, formaldehyde dehydrogenase. PMID- 8461036 TI - Initial characterization of the major mouse cytochrome P450 enzymes involved in the reductive metabolism of the hypoxic cytotoxin 3-amino-1,2,4-benzotriazine-1,4 di-N-oxide (tirapazamine, SR 4233, WIN 59075). AB - The benzotriazine di-N-oxide SR 4233 (tirapazamine, WIN 59075) is currently in phase I clinical trials as the lead compound in a series of novel and highly selective antitumour hypoxic cytotoxins. Reductive bioactivation is thought to proceed via a one-electron reduced, oxidizing nitroxide radical and also forms the inactive single N-oxide SR 4317 via radical disproportionation or a second one-electron reduction. In mouse liver microsomes reductive metabolism is catalysed predominantly by cytochrome P450 (70%) and cytochrome P450 reductase (30%). The aim of the present study was to examine which cytochrome P450 isozymes may be involved. Reduction of SR 4233 to SR 4317 was monitored by HPLC analysis. Metabolism by microsomes from both control and dexamethasone-induced BALB/c male mice was 70% inhibited by carbon monoxide. The cytochrome P450 inhibitor SKF 525A, following aerobic preincubation, also inhibited SR 4233 reduction by 58%. Reduction was induced 2-3-fold by dexamethasone and was not accountable by increases in cytochrome P450 reductase or DT-diaphorase. The induction data and the greater degree of inhibition of SR 4233 reduction by metyrapone compared to alpha-naphthoflavone suggested a possible involvement of Cyp2b, Cyp2c and Cyp3a cytochrome P450 subfamilies. Both Cyp3a (7.4-fold) and Cyp2b (1.8-fold) type enzymes were shown by western immunoblot analysis to be induced by dexamethasone, the latter correlating more closely with increased SR 4233 reductase activity and also with the 2-fold induction of benzphetamine N-demethylase, a Cyp2b-type enzyme. No inhibition of SR 4233 reduction was seen with erythromycin or cyclosporin A which act as substrates/inhibitors for Cyp3a-type enzymes, but inhibition was seen with p-nitrophenol and tolbutamide which are substrates for Cyp2el- and Cyp2c-type enzymes, respectively (11% and 25% inhibition in induced microsomes). SR 4233 itself inhibited benzphetamine N-demethylase, which is catalysed by Cyp2b-type enzymes but not erythromycin N-demethylase which is catalysed by Cyp3a-type isoforms. Immunoinhibition studies with epitope specific monoclonal antibodies were consistent with the major involvement of phenobarbitone- and steroid-inducible products of the Cyp2b and Cyp2c subfamilies. These forms contributed at least 53% and 26%, respectively, of the cytochrome P450-associated SR 4233 reductase activity in the induced microsomes. The findings support our earlier conclusion that cytochrome P450 is the major SR 4233 reductase in mouse liver and provides leads as to the possible involvement of specific isoforms in human tumours and normal tissues. PMID- 8461037 TI - Cytochrome P450-related differences between rats and mice in the metabolism of benzene, toluene and trichloroethylene in liver microsomes. AB - In evaluating the risks to humans of exposure to chemicals, the results of studies in rodents are sometimes used as a basis for extrapolation. It is therefore important to elucidate differences in metabolism among species. Differences in cytochrome P450-catalysed oxidation of benzene, toluene and trichloroethylene (TRI) between male Wistar rats and male B6C3F1 mice were investigated by immunoblot and immunoinhibition assays using monoclonal antibodies (MAbs) to cytochrome P450 (CYP1A1/2, CYP2B1/2, CYP2E1 and CYP2C11/6). Immunoblot analysis showed that anti-CYP2B1/2 did not detect any protein in either untreated rat or mouse liver microsomes, whereas with anti-CYP2E1 and/or anti-CYP1A1/2 a clear-cut band was seen more in liver microsomes from mice than from rats. Mouse liver microsomes had a greater monooxidation activity for benzene and TRI than rat liver microsomes; mice also had a higher rate of aromatic hydroxylation of toluene at low substrate concentration, but a low rate of side-chain oxidation when a high concentration of toluene was used. The metabolism of benzene was saturated in mice at around 0.23 mM, but the metabolism of the other two solvents was not saturated in either rats or mice at the low concentrations used. Anti-CYP2E1 inhibited the metabolism of benzene, toluene and TRI in microsomes from mice to a greater extent than in rats, while anti CYP2C11/6 inhibited their metabolism in rats to a greater extent than in mice; anti-CYP1A1/2 inhibited the metabolism of TRI only in microsomes from mice. These results indicate that (i) male B6C3F1 mice have more CYP2E1 and 1A1/2 than male Wistar rats, whereas rats have more CYP2C11/6 than mice; (ii) rats and mice express CYP2B1/2 but they are not immunochemically detectable; (iii) CYP2E1 and 2C11/6 in both species are responsible for the metabolism of benzene, toluene and TRI, whereas CYP1A1/2 in mice catalyses the oxidation of TRI. The differences in the metabolism of benzene, toluene and TRI in rats and in mice may therefore depend, at least in part, on differences in the distribution of P450 isozymes between the two species. PMID- 8461038 TI - Phase I and phase II xenobiotic reactions and metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in aggregating liver cell cultures. AB - Aggregating fetal liver cell cultures were tested for their ability to metabolize xenobiotics using ethoxycoumarin-O-deethylase (ECOD), as marker of phase I metabolism, and glutathione S-transferase (GST), as marker for phase II reactions. Significant basal activities, stable over 14 days in culture were measured for both ECOD and GST activities. The prototype cytochrome P450 inducers, 3-methylcholanthrene (3-MC) and phenobarbital (PB), increased ECOD and GST activities reaching an optimum 7 days after culturing, followed by a decline in activity. This decline was partially prevented by 1% dimethyl sulfoxide (DMSO) added chronically to the culture medium. DMSO was also found to induce ECOD activity and to a lesser extent GST activity. Furthermore, it potentiated in a dose-dependent manner the induction of ECOD by PB. The food-borne carcinogen 2 amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is metabolically transformed through a number of pathways in vivo. It was therefore used to examine the metabolic capacity in fetal and adult liver cell aggregates. Metabolism of MeIQx was mainly through N2-conjugation, resulting in formation of the N2-glucuronide and sulfamate conjugates for non-induced fetal liver cells. These metabolites were also found in large amounts in non-induced adult liver cells. Low levels of cytochrome P450-mediated ring-hydroxylated metabolites were detected in both non induced fetal and adult liver cells. After induction with arochlor (PCB) or 3-MC, the major pathway was ring-hydroxylation (cytochrome P450 dependent), followed by conjugation to beta-glucuronic or sulfuric acid. The presence of the glucuronide conjugate of N-hydroxy-MeIQx, a mutagenic metabolite, suggested an induction of P450 CYP1A2. The metabolism of MeIQx by liver cell aggregates is very similar to that observed in vivo and suggests that aggregating liver cell cultures are a useful model for in vitro metabolic studies in toxicology. PMID- 8461039 TI - Effect of rociverine on P450-dependent monooxygenases and its N-deethylation metabolism in rat liver microsomes. AB - Rociverine [2-(diethylamino)-1-methylethyl cis-1-hydroxy [bicyclohexyl]-2 carboxylate] citrate (ROC) is an antispasmodic agent therapeutically active in humans at doses of 0.5-1 mg/kg. This study investigated the effect of acute administration of the drug on hepatic microsomal cytochrome P450 (P450)-catalysed drug metabolism. Only high doses (> or = 100 mg/kg) of ROC were able to induce in rats the hepatic microsomal pentoxyresorufin O-depenthylase (PROD) and 16 beta testosterone hydroxylase activities both associated with P4502B1/2 and the erythromycin N-dimethylase (ErD) and 2 beta-testosterone hydroxylase activities both dependent on P4503A1/2. However, at 100 and 200 mg/kg of ROC, the 16 beta testosterone hydroxylase and PROD were the most induced activities, suggesting that P4502B1/2 are the isoforms most sensitive to ROC induction. Accordingly, ROC treatment enhanced, in a dose-dependent manner, the amount of P4502B1/2 and 3A1/2 in microsomes as assayed by western blotting. The northern blot analysis of ROC treated rat liver showed that the P4502B1/2 induction appears to be regulated at the mRNA level as in the induction by phenobarbital (PB). The oxidative metabolism of ROC with hepatic microsomes from control or PB- and ROC-induced rats resulted in a N-deethyl ROC derivative (major metabolite) and an unknown minor ROC derivative. The kinetic parameters for the N-deethylation of ROC were studied with purified P4502B1 and with microsomes from control or rats treated with various inducers (phenobarbital, ethanol, beta-naphthoflavone, dexamethasone and rociverine). It was found that phenobarbital-, dexamethasone- and rociverine induced microsomes deethylated ROC with a Vmax about five times higher than that (0.9 nmol/min/mg protein) of control microsomes, although with a similar affinity (Km approximately 0.3 mM). In a reconstituted system, the purified P4502B1 metabolized ROC with a high deethylation rate (22 nmol/min/nmol P450). Moreover, the ROC deethylation was inhibited by compounds such as hexobarbital, metyrapone and triacetyloleandomicin, selective inhibitors for P4502B and/or P4503A enzymes. On the other hand ROC, when added in vitro, inhibited the 16 beta- and 2 beta testosterone hydroxylases and the PROD and ErD activities. Taken together, these results indicate that the ROC-inducible P4502B and P4503A are involved in ROC deethylation. In conclusion, it has been demonstrated that ROC is a weak phenobarbital-like inducer of P450, probably able at high and reiterated doses to alter its own metabolism, at least in the rat liver. PMID- 8461040 TI - Effects of chronic low-level lead exposure on mRNA expression, ADP-ribosylation and photoaffinity labeling with [alpha-32P]guanine triphosphate-gamma azidoanilide of GTP-binding proteins in neurons isolated from the brain of neonatal and adult rats. AB - The effects of chronic lead exposure on mRNA expression, ADP-ribosylation and photoaffinity labeling with [alpha-32P]guanine triphosphate-gamma-azidoanilide ([32P]GTP-A) of alpha i or alpha s subunit of G protein were investigated in neurons isolated from the brain of neonatal and adult rats exposed to lead acetate or sodium acetate (for control). Rats were exposed by oral feeding for 10 days or 20 weeks to a low level of lead acetate or sodium acetate. The exposure started either prenatally or at an adult age. The expression of alpha i-mRNA in neurons obtained from the brain of control neonatal rats was significantly higher than that of the expression in samples obtained from the brain of control adult rats or the brain of rats exposed to lead at an adult age. The expression of alpha i-mRNA in neurons obtained from the brain of control neonatal rats, lead exposed neonatal rats and adult rats prenatally exposed to lead did not differ significantly. Chronic lead exposure did not affect the expression of alpha s mRNA in neurons obtained from the brain of neonatal and adult rats. The ADP ribosylation or the photoaffinity labeling with [32P]GTP-A of alpha i or alpha s subunits reflected the developmental pattern of the expression of alpha i or alpha s-mRNA. The incorporation of radioactivity in alpha i-subunit obtained from the brain of control neonatal rats, lead-exposed neonatal rats and rats prenatally exposed to lead was greater than the incorporation in alpha i-subunit obtained from the brain of control adult rats or rats exposed to lead at an adult age. The incorporation of radioactivity did not differ significantly in alpha s subunits obtained from control or lead-exposed neonatal and adult rats. These observations indicate that (1) the mRNA expression, ADP-ribosylation and photoaffinity labeling with [32P]GTP-A of alpha i-subunit decrease, whereas the mRNA expression, ADP-ribosylation and photoaffinity labeling with [32P]GTP-A of alpha s-subunit do not change as animals age after postnatal day 10, (2) chronic prenatal lead exposure delays the age-dependent decrease in mRNA expression, ADP ribosylation and photoaffinity labeling of alpha i subunit, and (3) chronic adult exposure does not cause these changes. PMID- 8461041 TI - Circadian rhythm of rat spleen cytoplasmic thymidine kinase. AB - The activity of thymidine kinase (TK, EC 2.7.1.21), the first enzyme of the thymidine phosphorylation pathway, was measured at various times over a 24-hr period in the spleens of Sprague-Dawley rats that had been housed under standardized conditions of light and dark for at least 4 weeks before the study. Spleen cytoplasmic TK activity was assayed with [2-14C]thymidine as substrate. Under "normal" light conditions (lights on 6:00 a.m.-6:00 p.m. and lights off 6:00 p.m.-6:00 a.m.), a circadian variation of TK activity was observed (P < 0.0001), Cosinor analysis) with peak activity (1.98 nmol product/hr/mg protein) at 1:00 a.m. (19 hr after light onset, HALO) and trough activity (0.40 nmol product/hr/mg protein) at 1:00 p.m. (7 HALO). Maximum enzyme activity exceeded minimum activity by approximately 5-fold. Reversing the light-dark cycle resulted in a corresponding shift in TK activity. Under these "reverse" conditions (lights on 6:00 p.m.-6:00 a.m. and lights off 6:00 a.m.-6:00 p.m.), a circadian variation in TK activity was also observed (P < 0.0001, Cosinor analysis) with peak activity (1.14 nmol product/hr/mg protein) at 12:00 noon (18 HALO) and trough activity (0.32 nmol/hr/mg protein) at 12:00 a.m. (6 HALO). Maximum enzyme activity exceeded minimum activity by approximately 4-fold. In summary, this study demonstrated for the first time that TK activity varies over a 24-hr period in association with the light-dark cycle. PMID- 8461042 TI - Alteration of calcium mobilization in endothelial cells by volatile anesthetics. AB - Halothane and isoflurane have different effects on the peripheral vasculature. Halothane decreases blood pressure primarily by decreasing cardiac contractility, whereas isoflurane acts primarily as a peripheral vasodilator. These peripheral vascular actions may result from different effects of the anesthetics on endothelial cell function and the release of endothelium-derived vasoactive mediators. The ability of these agents at clinically relevant concentrations to alter agonist-induced calcium mobilization in single cultured bovine aortic endothelial cells was tested using the fluorescent indicator fura-2. Neither halothane (0.3, 0.5, and 2 mM) or isoflurane (0.5 and 2 mM) altered basal calcium ([Ca]i = 49 +/- 5 nM); however, the calcium transient normally elicited by 10 nM bradykinin (peak [Ca]i = 307 +/- 22 nM) was inhibited significantly by halothane but not isoflurane. Neither anesthetic altered the calcium response to ATP (10 microM). These findings suggest that anesthetics may have specific effects on receptor-mediated endothelial cell functions that could influence hemodynamics. PMID- 8461043 TI - Protection of a rat tracheal epithelial cell line from paraquat toxicity by inhibition of glucose-6-phosphate dehydrogenase. AB - Transformed rat tracheal epithelial cells (U2) were found to be 3.6-fold more sensitive than lung fibroblasts (RLF) to paraquat. Although the toxic effects of paraquat are associated with the generation of very active superoxides, U2 cells contained higher levels of superoxide dismutase and catalase than RLF cells. On the other hand, the specific activities of both NADPH-cytochrome c reductase and glucose-6-phosphate dehydrogenase (G6DP) were 3- to 4-fold higher in U2 cells than in RLF cells. Treatment with dehydroepiandrosterone (DHEA) and epiandrosterone (EPI), G6PD inhibitors, significantly decreased the intracellular NADPH and protected U2 cells from paraquat toxicity. Since DHEA and EPI treatment did not affect the uptake of paraquat, our results suggest that paraquat sensitivity may depend on the redox cycling-associated activities of paraquat. PMID- 8461044 TI - Degradation of membrane phospholipids in the cultured human astroglial cell line UC-11MG during ATP depletion. AB - The exposure of brain cells to adverse conditions, such as ATP depletion, induces the degradation of membrane phospholipids and the accumulation of free fatty acids. We have investigated the mechanism of membrane breakdown in an in vitro cell injury model. Confluent cells from the human astroglial cell line UC-11MG were treated with sodium iodoacetate to deplete their intracellular ATP. Large amounts of saturated (palmitic acid) and unsaturated (oleic, linoleic and arachidonic acid) free fatty acids as well as diacylglycerols containing prelabeled fatty acids were released from the cells prior to the loss of plasma membrane integrity. The capacity of the cells to reincorporate free fatty acid into membrane phospholipids decreased in parallel with the loss of intracellular ATP, indicating the failure of the acyltransferase pathway. The addition of the phospholipase A2 inhibitors manoalide, mepacrine, or U-26384, or the phospholipase C inhibitor U-73122, reduced the severity of cell injury, but did not maintain cell viability. The addition of a battery of protease inhibitors with or without the phospholipase inhibitors had no protective effect. These results suggest that the activation of phospholipases A2 and C coupled with the loss of the reacylation process lead to the breakdown of membrane components during lethal cell injury. PMID- 8461045 TI - Isolation and characterization of a human ileocecal carcinoma cell line (HCT-8) subclone resistant to fluorodeoxyuridine. AB - A 5-fluoro-2'-deoxyuridine (FdUrd)-resistant subclone (Fd9XR) of HCT-8 (human ileocecal carcinoma) cells was established by two schedules of drug exposure. Initially, cells were exposed to short-term (3 hr) 100 nM FdUrd repeatedly (9 cycles over 8 months), and cells were then exposed to 10 nM FdUrd continuously. During this latter stage, a colony (Fd9XR) with fast growth rate was isolated, expanded, and characterized with respect to mechanisms of resistance to FdUrd and cross-resistance to other chemotherapeutic agents. Fd9XR cells were 1000-fold resistant to FdURD, but 3-fold more sensitive to 5-fluorouracil (FUra) than HCT-8 cells. After a 3-hr treatment with FdUrd, Fd9XR cells accumulated 6630-, 69-, and 3.7-fold less fluorodeoxyuridylate (FdUMP), fluorouridine triphosphate (FUTP) and acid-insoluble materials, respectively, than HCT-8 cells. However, when FUra was substituted for FdUrd, Fd9XR cells accumulated 9.2-, 3.1-, and 2.3-fold more FdUMP, FUTP and acid-insoluble materials, respectively, than HCT-8 cells. Fd9XR and HCT-8 were similar in their growth rates, combined pools of 5,10 methylenetetrahydrofolates (5,10-CH2H4PteGlun) and tetrahydrofolates (H4PTeGlun), thymidine phosphorylase (TP) activity, and level and activity of thymidylate synthase (TS). In contrast, thymidine kinase (TK) activity of Fd9XR was 0.23 and 0.35% of that of HCT-8, for thymidine (dThd) and FdUrd as substrates, respectively. Furthermore, Fd9XR cells exhibited greater sensitivity to the antifolate TS inhibitor ICI D1694 and to methotrexate (MTX) than HCT-8 cells. In addition, dThd alone and in combination with hypoxanthine did not offer any protection against the cytotoxic effect of ICI D1694 in Fd9XR cells. These results indicate that in Fd9XR cells (1) TK deficiency is the primary mechanism of resistance to FdUrd; (2) the greater sensitivity to FUra was associated with higher pools of FdUMP and FUTP with a subsequently higher level of incorporation into cellular RNA; and (3) antifolate compounds, e.g. ICI D1694 and MTX, could be useful agents in the treatment of FdUrd-resistant tumors associated with decreased TK activity and decreased capacity of utilizing dThd. PMID- 8461046 TI - Plasmodium falciparum: effects of amantadine, an antiviral, on chloroquine resistant and -sensitive parasites in vitro and its influence on chloroquine activity. AB - The lysosomotropic nature of amantadine suggested potential as an antimalarial. Sensitivity tests to amantadine hydrochloride alone and in combination with chloroquine were carried out in 96-well microtitre plates using the tritiated hypoxanthine uptake method to measure parasite growth. Amantadine alone has antimalarial activity. Amantadine is more potent against chloroquine-resistant strains. Combinations of amantadine and chloroquine result in slight synergy in both resistant and sensitive strains. PMID- 8461048 TI - Stabilization of S-adenosylmethionine decarboxylase by aminoguanidine. AB - Aminoguanidine, an inhibitor of copper-containing amine oxidases, is often used in cell culture studies to prevent the oxidation of added polyamines or their derivatives by the amine oxidase present in bovine serum. However, in the present study, we demonstrate that aminoguanidine, besides affecting the degradation of polyamines, may affect one of the important regulatory enzymes in the biosynthesis of polyamines, namely S-adenosylmethionine decarboxylase (AdoMetDC). Aminoguanidine was shown to induce a 2-3-fold increase in the AdoMetDC levels in L1210 cells. This increase was fully explained by a stabilization of the enzyme, probably caused by the binding of aminoguanidine to the active site of AdoMetDC. PMID- 8461047 TI - Metabolism of phenacetin in V79 Chinese hamster cell cultures expressing rat liver cytochrome P4501A2 compared to isolated rat hepatocytes. AB - In a genetically engineered V79 cell line (XEMd-MZ) expressing rat cytochrome P4501A2 the activity of phenacetin-O-deethylase was determined and compared with freshly isolated rat hepatocytes. In the V79 cells the apparent Km was 0.99 microM (N = 4), compared to the high affinity Km (0.23 microM, N = 4) found in freshly isolated rat hepatocytes, where as the Vmax found in the XEMd-MZ cells (14.90 pmol/min/10(6) cells) corresponded to the Vmax for the high affinity site of the hepatocytes (18.2 pmol/min/10(-6) cells). The metabolic capacity of phenacetin was quantitatively comparable to that of freshly isolated hepatocytes on a cell to cell basis. PMID- 8461049 TI - Effect of folate diastereoisomers on the binding of 5-fluoro-2'-deoxyuridine-5' monophosphate to thymidylate synthase. AB - A series of natural and unnatural stereoisomers of reduced folate coenzymes have been studied for their capacity to facilitate binding of 5-fluoro-2'-dUMP (FdUMP) to bacterial thymidylate synthase (TS). The natural cosubstrate for the enzyme, (6R)-5,10-methylene-tetrahydrofolate (CH2-H4-folate), was 4-fold more potent than the unnatural 6S-form in promoting FdUMP binding to TS, but in a racemic mixture the effect of the 6R-form was not affected by the 6S-form. FdUMP binding to TS was also stimulated by tetrahydrofolate and dihydrofolate (85% and 30% as compared to (6RS)-CH2-H4-folate, respectively), but not by the stereoisomers of 5 methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate (leucovorin). These results suggest that folates, which are not a natural cosubstrate for TS, have an additional role in facilitating FdUMP binding to TS. PMID- 8461050 TI - Sulphate conjugation of minoxidil in rat skin. AB - Minoxidil sulphotransferase (MST) activity was determined in the cytosolic fraction of rat skin and liver. MST of rat skin is similar to the P (phenol)-form of phenosulphotransferase (PST) of human tissues with respect to thermostability and inhibition by 2,6-dichloro-4-nitrophenol (DCNP). p-Nitrophenol, a prototype substrate of human P-PST form, inhibits MST at micromolar concentration while millimolar concentrations of dopamine and tyramine, substrates of human M (monoamine)-PST, are required to elicit a similar degree of inhibition. The enzymatic transfer of 35S from sodium 35sulphate to minoxidil was also demonstrated suggesting that the rat skin is potentially capable of synthesizing 3'-phosphoadenosine-5'-phosphosulphate (PAPS) from inorganic sulphate and utilizing it for the biosynthesis of minoxidil sulphate, its active metabolite. Thus, it is conceivable that the pharmacological action of minoxidil as a promoter of hair growth could be carried out by the cutaneous tissues without the contribution of hepatic or other extrahepatic organs. PMID- 8461051 TI - Clearance of N-nitrosodimethylamine and N-nitrosodiethylamine by the perfused rat liver. Relationship to the Km and Vmax for nitrosamine metabolism. AB - The first-pass clearance of dietary N-nitrosodimethylamine (NDMA) by the liver is the most important factor in the pharmacokinetics of this carcinogen in the rat, but is less important in the pharmacokinetics of N-nitrosodiethylamine (NDEA). The reason for the difference in clearance of these two nitrosamines is not known. These experiments were carried out to see whether the general characteristics of the clearance of these two carcinogens in vivo could be reproduced in the perfused liver, and whether the clearance could be correlated with the Michaelis-Menten parameters Km and Vmax for their metabolism. If this could be done one would be able to predict the possible extent of first-pass clearance of nitrosamines in man from measurement of Km and Vmax for nitrosamine metabolism by the human liver. The Km (22 microM) and Vmax (10.2 and 13.4 nmol/g liver/min) for the metabolism of NDMA by slices from two human livers, the inhibition of that metabolism by ethanol (Ki 0.5 microM), and the rate of N-7 methylation of DNA when slices are incubated with NDMA, were measured. These results are similar to those reported previously with rat liver. The Km (27 microM) for the metabolism of NDEA by rat liver slices and the inhibition of that metabolism by ethanol (Ki 1 microM) were estimated from the rate of ethylation of the DNA of the slices. The clearance of both these nitrosamines by the perfused rat liver was measured, and the results appeared to parallel those in vivo with a striking difference between the clearance of NDMA and NDEA. The maximal rate of clearance of NDMA was 11.2 nmol/g liver/min and of NDEA 8.9 nmol/g liver/min, similar to the Vmax for metabolism of NDMA by liver slices and to the estimated maximal rate of liver metabolism of both nitrosamines in the living rat. However, although the Km for metabolism of these two nitrosamines by liver slices is similar (about 25 microM), the logarithmic mean sinusoidal concentration [see Bass and Keiding, Biochem Pharmacol 37: 1425-1431, 1988] giving half maximal clearance during perfusion (the equivalent to Km) was 2.3 microM for NDMA and 10.6 microM for NDEA. The almost 5-fold difference between these two values is the basis for the difference between the clearance of the two nitrosamines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8461052 TI - Purification and immunological characterization of pigeon serum butyrylcholinesterase. Implications on environmental monitoring and toxicological testing of birds. AB - Butyrylcholinesterase (EC 3.1.1.8) (BChE) was purified from pigeon serum to electrophoretic homogeneity by a four-step procedure involving blue sepharose CL 6B chromatography, ion exchange chromatography, procainamide affinity chromatography and gel filtration. An overall 2789-fold purification was achieved, with a final specific activity of 61.35 mumol/min/mg. The purified enzyme separated into two peaks when filtered through a column of Sephacryl S 300, a smaller peak containing the tetrameric form of BChE (C4) and a larger peak containing the monomeric form of BChE (C1). Native polyacrylamide gel electrophoresis (PAGE) of both peaks revealed single protein bands which coincided with esterase activity, with approximate M(r) values of 84,000 and 340,000, respectively. The C1 monomer represented 85-90% of the activity found in the pigeon serum. It is not clear whether this polymorphism of BChE in vertebrates contributes to the wider inter-individual variations observed in xenobiotics elimination kinetics and in the response to the pharmacological and toxic effects of pesticides. PAGE of the monomeric form of the enzyme in the presence of sodium dodecyl sulphate showed only one protein band with a M(r) of 84,000, while that of the tetrameric form revealed two bands, a major protein band (84,000) and a minor band (170,000), representing the monomer and the dimer of the dissociated tetrameric BChE enzyme under reducing conditions. Highly specific polyclonal antibodies were raised in rabbits against the purified enzyme. These antibodies cross-reacted with other avian BChEs, a criterion which make them useful for the immunopurification of other BChEs from different species as well as for biomonitoring and toxicological studies on the role of esterases as an indicator of avian exposure to organophosphorous pesticides. PMID- 8461053 TI - Effects of the synthetic anti-oxidant, probucol, on the U937 monoblastoid cell line. AB - Probucol is a clinically important drug that decreases plasma cholesterol in humans and has a marked anti-atherogenic effect in hyperlipidaemic Watanabe rabbits. The action of probucol in this animal model has been partly attributed to its anti-oxidant abilities. Probucol can decrease the oxidative modification of low-density lipoprotein and hence diminish its uptake by macrophages. In this paper, we have examined the effect of probucol on the monoblastic cell line U937 and on U937 cells induced to differentiate towards a macrophage phenotype by 1,25 dihydroxycholecalciferol (DHCC), tumour necrosis factor-alpha (TNF-alpha) or phorbol myristate acetate (PMA). We found that probucol enhanced the proliferation of undifferentiated U937 cells. Probucol also enhanced proliferation in cultures that had been pre-treated with DHCC or TNF-alpha, but had no effect on cultures that had been pre-treated with PMA. In contrast, when U937 cells were treated simultaneously with probucol and DHCC or TNF-alpha, there was a more marked decrease in proliferation than was induced by these agents in the absence of probucol. Probucol had little effect on the phenotype of resultant cells. The surface expression of CD13 (aminopeptidase N), CD4, CD35 (C3b receptor), CD64 (Fc gamma RI), CD71 (transferrin receptor) and HLA Class II was not affected by probucol. Probucol treatment led to a small increase in the surface expression of CD16 (Fc gamma RIII) in TNF-alpha treated cells and to a small decrease in the expression of CD14 (a monocyte marker) in PMA-treated cells. The induction of c-fgr mRNA and TNF-alpha mRNA by DHCC or PMA or TNF-alpha was not significantly altered in the presence of probucol. The affect of probucol on U937 cells does not appear to be due to its anti-oxidant abilities because butylated hydroxytoluene (BHT), an equally powerful anti-oxidant, did not have the same effect on the cell proliferation as probucol and because no changes were detected in the levels of lipid peroxidation in U937 cell culture supernatants. PMID- 8461054 TI - The distribution of fibro-fatty atherosclerotic lesions in the aortae of casein- and cholesterol-fed rabbits. AB - Atherosclerotic lesions were induced in the aortas of 50 rabbits by feeding a semi-purified cholesterol-free casein diet or normal rabbit chow with a low level of added cholesterol for 6 or 10 months. Following perfusion fixation, the aortae from these animals were opened along their length, stained with oil red O and photographed en face. Orifice associated lesions were mapped by measuring radial lesion length at 10 degrees intervals circumferentially around ostia. Histology of these lesions revealed abundant smooth muscle cells surrounded by collagen and elastin in the extracellular matrix, typical of fibrous plaques, as well as oil red O staining lipid and some macrophage derived foam cells. These fibro-fatty lesions were found distal and lateral to ostia, at the same locations as fatty streaks seen in rabbits fed a 2% cholesterol diet for 1 week to 2 months in previous studies. The results of this study show that in moderately hypercholesterolemic rabbits fed an atherogenic diet for 6 to 10 months, advanced atherosclerotic plaques develop in the same location as the fatty streaks seen in short term experiments. PMID- 8461055 TI - Aortic esterified cholesterol is not superior to total cholesterol as a measure of atherosclerosis severity in cholesterol-fed rabbits. PMID- 8461056 TI - Can lipoprotein lipase be the culprit in cholesteryl ester accretion in smooth muscle cells in atheroma? AB - Bovine aortic smooth muscle cells and human skin fibroblasts were incubated with beta-very low density lipoprotein (beta VLDL) isolated from cholesterol-fed rabbits and labeled with [3H]cholesteryl oleate. Addition of lipoprotein lipase resulted in a 3.2-4.8-fold increase in cell associated radioactivity of which 45 61% was in free cholesterol, i.e., derived after intracellular hydrolysis. After exposure of smooth muscle cells to beta VLDL for up to 9 days and 60 min sodium heparin wash at 4 degrees C to remove extracellular surface bound lipoprotein, cellular cholesterol increase was 2 micrograms in controls and in the presence of lipoprotein lipase (LPL) it was tenfold higher. Addition of [3H]cholesteryl ester labeled beta VLDL during the last 48 h of incubation showed that 30-40% of total cellular label was in free cholesterol. This value represents the minimal cellular uptake of the added lipoprotein cholesteryl ester. Addition of recombinant apolipoprotein (apo) E to smooth muscle cells incubated with beta VLDL and [3H]oleate induced no further increase in [3H]cholesteryl oleate. We propose that following LPL-mediated binding of beta VLDL to heparan sulphate, this complex either undergoes endocytosis, or translocation of cholesteryl ester into the smooth muscle cells (SMC) occurs without endocytosis of the entire particle. The present results indicate that in the aortic wall macrophage-derived lipoprotein lipase could play a role in cholesteryl ester accretion in smooth muscle cells during atherogenesis. PMID- 8461057 TI - Lipoprotein(a): relation to other risk factors and genetic heritability. Results from a Dutch parent-twin study. AB - We measured plasma levels of lipoprotein(a) (Lp(a)) in a sample of 152 Dutch adolescent mono- and dizygotic twin pairs and their parents. The distribution of Lp(a) levels was skewed, with the highest frequencies at low levels and was similar for adult men and women and their children. The relationship of Lp(a) concentrations with other lipoprotein and apolipoprotein risk factors for coronary heart disease and with lathosterol, an indicator of whole-body cholesterol synthesis, was studied dependent on sex and generation. In mothers and children there was a small positive correlation between Lp(a) levels and plasma cholesterol and apolipoprotein (apo) B. In mothers and daughters there also was a correlation between Lp(a) and LDL cholesterol levels. No correlation was found between Lp(a) levels and plasma lathosterol, suggesting that there is no relationship between Lp(a) levels and cholesterol synthesis. Associations among family members, i.e. between monozygotic and dizygotic twins and between parents and offspring were used to study familial transmission of Lp(a) levels. Results showed that almost all of the variance in Lp(a) concentrations was accounted for by genetic heritability. A small, but significant, sex difference in heritability was observed, but heritabilities were the same in parents and offspring. Heritability estimates were 93% for females and 98% for males. No evidence was found for assortative mating or for the influence of a shared family environment. These results indicate that nearly all variance in Lp(a) concentrations that is not accounted for by the apo(a) size polymorphism, is also under genetic control. PMID- 8461058 TI - Effect of low density lipoprotein on monocyte adhesiveness to endothelial cells in vitro. AB - Adhesion of monocytes to the endothelium is an early event in the development of atherosclerosis. The possibility that low density lipoproteins enhance this process by activating monocytes was investigated using an in vitro adhesion test on endothelial cell monolayer cultures. Preincubation of monocytes with low density lipoprotein (LDL) (100 micrograms LDL protein/l x 10(6) cells/ml) for 15 min induced a 70% increase in adhesion to endothelial cells with a maximal effect at 100 micrograms LDL protein/ml and a short latency of effect (2 min). Anti-LDL receptor antibody, which inhibited LDL binding, blocked this activation. The LDL effect appeared to depend on receptor binding of LDL rather than on receptor mediated endocytosis, since preincubation of monocytes with LDL at either 4 degrees C or 37 degrees C resulted in the same stimulation of adhesion. A cytofluorimetric study using integrin monoclonal antibodies (MAbs) against CD18 and CD11b did not reveal any increase in expression of the integrins on the surface of LDL-activated monocytes. However, a 30-min preincubation of monocytes with anti-CD18 abolished the LDL-activated adhesion. These results indicate that LDL induces a rapid activation of monocyte adhesiveness to endothelial cells. This effect appears to be mediated by interaction of LDL with its receptor rather than LDL-receptor complex internalization or integrin membrane mobilization from intracellular pools. The integrin system nevertheless appears to be involved. PMID- 8461060 TI - Levels of plasma factor VII and factor VII activated forms as a function of plasma triglyceride levels. AB - It has been shown that triglyceride levels are one of the determinants of factor VII levels. In this study we have simultaneously evaluated, in a group of 102 healthy individuals, the different forms of factor VII, namely factor VII mass, factor VII coagulant activity, activated factor VII double-chain form and factor VII-phospholipid complex, in relation to triglyceridaemia. The data showed a highly significant correlation of factor VII mass, factor VII coagulant activity and factor VII-phospholipid complex with triglycerides. No correlation was observed between the activated factor VII double-chain form and triglycerides. These data, together with analysis of the linear and orthogonal regression slopes, suggest that increase of plasma factor VII coagulant activity as a function of plasma triglyceride levels is attributable to an increase in both mass and activity of factor VII and that the increase in activity is dependent on an increase of factor VII-phospholipid complex rather than activated factor VII double-chain form. The ratio between the slopes of the regression straight line of factor VII mass and factor VII-phospholipid complex in relation to triglycerides was 2.23 (95% confidence limits 1.74-2.50), thus indicating that the contribution of factor VII mass is prevalent over that of the factor VII phospholipid complex. PMID- 8461059 TI - Hypercholesterolemia in non-insulin-dependent diabetes mellitus: different effect of simvastatin on VLDL and LDL cholesterol levels. AB - Non-insulin-dependent diabetes mellitus (NIDDM) is often characterized by an increase in VLDL-triglyceride, VLDL-cholesterol, LDL-cholesterol and a reduction in HDL-cholesterol. HMG-CoA reductase inhibitors significantly lower cholesterol rates and have an indirect effect on the LDL receptor. We measured the effect of simvastatin in 28 hypercholesterolemic subjects, including 14 with NIDDM in good metabolic control (HbAIc 7.8% +/- 1.3%). A 24-week treatment with 10 mg/day (weeks 1-4), 20 mg/day (weeks 5-8) and 40 mg/day (weeks 9-24) simvastatin revealed different responses in diabetic and non-diabetic patients. Total cholesterol, LDL-cholesterol and apo B decreased significantly in both groups (less in the diabetics), whereas only NIDDM patients displayed a significant reduction in VLDL-cholesterol and VLDL-apo B. In the non-diabetics, the reduction in plasma cholesterol was mainly confined to the LDL fraction (276 +/- 65 vs. 132 +/- 28 mg/dl), whereas a significant fall in VLDL-cholesterol (45 +/- 19 vs. 21 +/- 10 mg/dl) was more evident in the NIDDM patients. Simvastatin also influenced plasma apo B levels (221 +/- 33 vs 134 +/- 23 mg/dl in non-diabetics and 182 +/- 44 vs. 134 +/- 30 mg/dl in diabetics). Significant reduction of apo B, LDL-apo B (205 +/- 39 vs. 128 +/- 23 mg/dl) in the non-diabetics and VLDL-apo B (16 +/- 5 vs. 9 +/- 2 mg/dl) in the diabetics, indicates that the VLDL are primarily concerned when statins are administered in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461061 TI - Predisposition to LDL oxidation in patients with and without angiographically established coronary artery disease. AB - Oxidative modification of low density lipoprotein (LDL) may play an important role in the mechanism of atherosclerotic damage to blood vessels. In the present study the LDL isolated from the plasmas of 73 coronary artery disease (CAD) patients, 28 valvular heart disease (VHD) patients, 59 subjects affected by type IIa hyperlipoproteinemia and 71 controls was oxidatively modified by incubation with copper ions. In 15 CAD and 15 Type IIa patients and 15 controls the LDL chemical composition and polyunsaturated fatty acid (PUFA) content were also measured. Differences in the LDL susceptibilities to lipid peroxidation were studied by measuring the changes of fluorescence intensity. The lag phase in the CAD patients was found to be significantly lower than in the VHD and controls (P < 0.001). The lag phase in the type IIa patients was significantly higher than in the CAD patients (P < 0.01), and significantly lower than the VHD and controls (P < 0.01). The LDL isolated from the type IIa patients had an increase in the relative content of free and esterified cholesterol (P < 0.05), while the CAD patients had a decrease in the relative content of free cholesterol (P < 0.05), and an increase in the relative content of protein (P < 0.05). The lowest value of the LDL cholesterol to protein ratio and LDL size, was found in the CAD patients (P < 0.05). When expressed in micrograms/mg LDL cholesterol, the concentration of the LDL PUFAs was significantly higher in the CAD group than in the others (P < 0.05). The LDL alpha-tocopherol concentration was quite similar in the different groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461062 TI - Effect of interleukin-1 receptor antagonist on vascular smooth muscle cell proliferation. AB - The development of the atheromatous plaque is largely dependent on vascular smooth muscle cell proliferation and production of biologically active compounds such as cytokines and growth factors. Cytokines such as IL-1 derived from blood vessel wall may contribute to regional defense or pathology. Neutralization of the effects mediated by IL-1 by a receptor antagonist specific for IL-1 alpha and IL-1 beta has been shown to reduce the possible pathologic consequences induced by IL-1 in the regional environment. The effect of human recombinant interleukin 1 receptor antagonist (hrIL-1ra), a new member of the IL-1 family, has been assessed on modulating vascular smooth muscle cell (VSMC) proliferation in the rat. A significant dose- and time-dependent reduction of DNA synthesis was observed when hrIL-1ra was added to the cell cultures. The maximum inhibitory effect was seen using IL-1ra at a concentration of 250 ng/ml and after 48 h incubation with cultured vascular smooth muscle cells. Furthermore, hrIL-1ra inhibited VSMC growth in the presence of exogenous mitogenic doses of IL-1 alpha. The addition of indomethacin to the cultures did not modify the inhibitory events. These data suggest a possible pharmacologic role for IL-1ra in inhibiting VSMC proliferation by possibly interfering with the autocrine regulatory pathway of IL-1. PMID- 8461063 TI - Effect of testosterone on atherogenesis in cholesterol-fed rabbits with similar plasma cholesterol levels. AB - The aim was to examine the effect of testosterone on atherogenesis in cholesterol fed, castrated male rabbits not mediated via different plasma cholesterol levels. The rabbits in the testosterone group (n = 19) and in the placebo group (n = 17) were injected intramuscularly twice weekly for 17 weeks with 25 mg testosterone enantate and placebo, respectively, reaching plasma testosterone levels of 50-150 nmol/l in the testosterone group. No effect of testosterone on liver function or body weight was detected, but at week 15 mean blood pressure was 75 +/- 2 mmHg (mean +/- S.E.) in the testosterone group compared with 69 +/- 2 mmHg in the placebo group (P < 0.05). To reduce variation in plasma cholesterol between the two groups, the amount of cholesterol fed to each rabbit was adjusted on the basis of weekly determinations of plasma cholesterol; the mean plasma cholesterol levels during the 17 weeks were 20.9 +/- 1.0 and 20.4 +/- 0.9 mmol/l for the placebo and testosterone groups. In the intima-inner medias of the aortic arch, the thoracic and the abdominal aorta there were no consistent significant differences in aortic cholesterol content, expressed either as nmol/cm2 or nmol/mg protein, between the two groups. However, the aortic cholesterol content tended to be lower in the testosterone group than in the placebo group. These findings suggest that in cholesterol-fed, castrated male rabbits, testosterone does not promote atherogenesis by an effect directly on the arterial wall. PMID- 8461064 TI - Lipoprotein(a) is not associated with coronary heart disease in the elderly: cross-sectional data from the Dubbo study. AB - Lipoprotein(a) (Lp(a)) may be an independent risk factor for cardiovascular disease. We have examined Lp(a) concentration in 1202 males and 1512 females, aged 60 years and older, who were participants in an ongoing prospective study of cardiovascular disease in the elderly. This report relates to cross-sectional data at study entry. Median Lp(a) concentration was significantly higher in females than in males (P < 0.001), but did not vary with age. Lp(a) concentration rank was significantly correlated with total (r = 0.16, P < 0.001) and LDL cholesterol (r = 0.19, P < 0.001), but this relationship disappeared after adjustment of LDL cholesterol for Lp(a) cholesterol content. Twenty-four percent of males and 17% of females had prevalent coronary heart disease (CHD) at study entry based on non-invasive criteria. Median Lp(a) concentration was slightly higher in those subjects with CHD, compared with those without CHD, but the difference was not statistically significant (P > 0.20). In a multiple logistic model, the following variables were independent predictors of CHD in this elderly population: age, hypertension (males only), family history of CHD, HDL cholesterol and triglycerides (females only), but not total cholesterol or Lp(a). These relationships were similar whether or not the model included Lp(a) concentration. The findings do require confirmation in the prospective study now in progress. PMID- 8461065 TI - Effect of dietary hydrogenated corn oil (trans-octadecenoate rich oil) on plasma and hepatic cholesterol metabolism in the hamster. AB - The effect of dietary hydrogenated corn oil (trans-octadecenoate-rich oil) on plasma cholesterol and triglyceride concentrations was compared with dietary palmitic acid in hamsters given a cholesterol-rich diet. The addition of dietary palmitic acid and hydrogenated corn oil accelerated the increase in plasma VLDL- and LDL-cholesterol levels and plasma triglyceride level induced by dietary cholesterol loading. Dietary cholesterol, palmitic acid and hydrogenated corn oil showed no effect on plasma HDL-cholesterol concentration. A decrease in hepatic LDL receptor activity was seen in animals fed a diet supplemented with cholesterol in combination with palmitic acid or hydrogenated corn oil in comparison with animals fed a diet supplemented with cholesterol alone. Hydrogenated corn oil (trans-octadecenoate-rich oil) appears to potentiate the effect of dietary cholesterol in elevating the plasma VLDL- and LDL-cholesterol levels through the suppression of hepatic LDL receptor activity. trans Octadecenoate in dietary hydrogenated corn oil may be as atherogenic as dietary palmitic acid due to a suppression of hepatic LDL receptors in the presence of dietary cholesterol loading. PMID- 8461066 TI - Conflict of interest. PMID- 8461067 TI - [4 sources to knowledge]. PMID- 8461068 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 14-1993. A 74-year-old woman with hyperparathyroidism and an osteolytic lesion in the humerus. PMID- 8461069 TI - The outcome of a free autogenous semitendinosus tendon graft in human anterior cruciate reconstructive surgery: a histological study. AB - This report illustrates the outcome of a free human autogenous semitendinosus tendon graft placed in the knee under arthroscopic control for anterior cruciate ligament reconstruction. The tendon graft showed signs of injury by localized loss of normal histochemical staining properties. The cellularity was not diminished in an early (3-week) specimen. The resultant composite anterior cruciate ligament consisted of two distinct areas: tendon graft and surrounding fibrous tissue. The tendon maintained gross and microscopic characteristics of the original tendon. The tissue surrounding the tendon graft had a disorganized cellular pattern and hypervascularity. The tendon graft in this study did not show gross or microscopic evidence of death and reorganization. Previous reports have led to erroneous conclusions concerning the outcome of a free tendon graft due to inaccurate biopsy site of the reorganizing fibrous tissue surrounding the tendon graft. PMID- 8461070 TI - A comparison of the doubled semitendinosus/gracilis and central third of the patellar tendon autografts in arthroscopic anterior cruciate ligament reconstruction. AB - The purpose of this study was to compare the postoperative success and stability of two different autografts used to reconstruct the anterior cruciate ligament (ACL): doubled semitendinosus/gracilis (DST&G) and bone-patellar tendon-bone (PAT). Ninety-one young (x = 25.4 years), active patients were available for an average follow-up of 36.4 months and included 55 patients in the PAT group and 36 in the DST&G group. No patients had previously undergone ACL reconstruction. Knee stability data were obtained yearly and included scores from the Lysholm questionnaire, Lachman exam, and KT-1000 arthrometer at 30 pounds (KT30) and maximum pull (KTMAX). Both autografts were of comparable size, tension, and isometricity. Two separate factorial multivariate analyses of variance (MANOVA) were used to compare the two series for 3 follow-up years in the categories acute and chronic (A versus C) and meniscectomy and no meniscectomy (M versus NM). Results indicated that in all categories and follow-up years, PAT patients had consistently greater knee stability compared with the DST&G group. Overall MANOVA results showed significantly lower (p < 0.01) Lachman scores in PAT versus DST&G in each of the 3 follow-up years. Significantly lower (p < 0.05) KT30 and KTMAX values were also observed for PAT compared with DST&G in year 1. MANOVA results also showed lower (p < 0.01) Lachman scores in PAT-A versus DST&G-A for 3 follow up years. Lachman scores in PAT-NM patients were lower (p < 0.01) for postop years 1 and 2 compared with DST&G-NM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461071 TI - The ligamentization process: a 4 year case study following ACL reconstruction with a semitendinosis graft. AB - This study evaluates the histological and biochemical changes that occurred in a semitendinosis autograft 4 years after intraarticular placement as an anterior cruciate ligament (ACL) substitute in a human patient. The graft was harvested during total knee replacement. Comparison to harvested ACL and hamstring tendon was made. Changes in collagen crimp pattern, cell type, glycosaminoglycan composition, and collagen crosslinking were present between the ACL autograft and the hamstring tendon. The appearance and biochemical properties of the semitendinosis autograft and the native ACL were similar 4 years following intraarticular placement. These observed phenomena could be attributed to functional adaptation, supporting the concept of ligamentization. PMID- 8461072 TI - Radiographic analysis of femoral interference screw placement during ACL reconstruction: endoscopic versus open technique. AB - Fifty patients with anterior cruciate ligament reconstruction using a bone patellar tendon-bone autograft performed by two techniques were evaluated roentgenographically to compare the position of the femoral interference screws. Group I consisted of 25 patients in whom the screw was placed using a distal lateral femoral incision (the two-incision technique). Group II patients underwent arthroscopically assisted intraarticular placement of the screw. These patients were then evaluated with anterior-posterior (AP) and lateral roentgenograms. We observed that the AP and lateral screw angles were significantly different with the two techniques. In addition, the endoscopic placement of the femoral screw had an associated divergence of the screw relative to the bone plug in nine of 25 patients compared with zero of 25 in the open group. In conclusion, radiographic differences do exist between femoral interference screws placed for fixation of an ACL graft using the open approach and those placed endoscopically. Although the clinical significance of these differences is not known, we raise the question of greater divergence in femoral interference screw placement with the newer intraarticular femoral interference screw placement techniques. PMID- 8461073 TI - Scoring of patellofemoral disorders. AB - A new questionnaire was used to evaluate subjective symptoms and functional limitations in patellofemoral disorders. The questionnaire was completed independently by four groups of female subjects: controls (N = 17), and subjects with anterior knee pain (N = 16), patellar subluxation (N = 16), and patellar dislocation (N = 19). The questionnaire mean scores for the groups were 100, 83, 68, and 62 points, respectively (p < 0.0001). The items dealing with abnormal painful patellar movements (subluxations) (p < 0.0001), limp (p < 0.0001), pain (p < 0.0001), running (p < 0.0001), climbing stairs (p < 0.0001), and prolonged sitting with the knees flexed (p < 0.0001) differentiated the study groups most clearly. We recommend that these questions be asked when taking a standardized clinical history of an anterior knee pain patient. We also analyzed lateral patellar tilt and displacement by magnetic resonance imaging (MRI) in 28 subjects with patellar subluxation or dislocation. Low questionnaire sum score correlated best with increased lateral patellar tilt measured during quadriceps contraction in 0 degree knee flexion. It seems that a tendency to lateral patellar tilt during quadriceps contraction causes anterior knee pain and can be imaged in knee extension when the patella is not fully supported by femoral condyles. PMID- 8461074 TI - Two cases of dorsal defect of the patella with arthroscopically visible cartilage surface perforations. AB - Dorsal defect of the patella is an approximately 1-cm, circular, radiolucent, well-marginated benign lesion invariably located in the superlateral aspect of the patella. Only approximately 50 cases have been described in the world literature, of which < 10 cases have been studied histologically. We report two patients with bilateral, virtually symmetrical, dorsal defects of the patella and describe the arthroscopic and histologic findings. Case 1 was a 14-year-old girl and case 2 was a 35-year-old man. Cartilage perforations were seen via arthroscopy on the cartilage surface of both knees. The pathophysiology of this disorder remains to be clarified, although van Holsbeeck et al. proposed that vastus lateralis traction injury in the ossification process of the patella may be involved, as in the case of bipartite patella. The present arthroscopic and histological findings support this hypothesis. PMID- 8461075 TI - The efficacy of Na-naproxen after diagnostic and therapeutic arthroscopy of the knee joint. AB - The purpose of the study was to evaluate the effect of na-naproxen after diagnostic arthroscopy and arthroscopic surgery of the knee joint. In a double blind trial, 41 patients were randomized to treatment with na-naproxen, and 46 patients were given placebo after surgery. For additional analgesia, patients got acetaminophen if necessary. In patients who underwent arthroscopic surgery, there were no differences between those treated with na-naproxen and those who received placebo in pain levels, but patients receiving na-naproxen had significantly less need for additional analgesia and returned significantly more quickly to work than patients receiving placebo (median 10 versus 30 days). In patients who had only diagnostic arthroscopy, there were no differences between the na-naproxen and placebo groups. PMID- 8461076 TI - Acute traumatic knee hemarthrosis. AB - A rapidly developing hemarthrosis in an acutely injured knee is reported to be associated with "surgically significant" lesions, such as anterior cruciate ligament tears, meniscus tears, and osteochondral fractures, in < or = 90% of cases. We report two cases of adult men who showed signs of such acute hemarthroses in stable knees after significant trauma. Neither had significant intraarticular pathology, such as meniscal, articular, or ligamentous injury, at arthroscopy. Persistent postarthroscopic bleeding led to additional diagnostic testing that found mild factor VIII deficiency. Hemophilia A and other clotting disorders should be considered by arthroscopic surgeons as a possible cause of a posttraumatic hemarthrosis. PMID- 8461077 TI - Pain relief after arthroscopic surgery of the knee: a prospective, randomized, and blinded assessment of bupivacaine and bupivacaine with adrenaline. AB - A prospective, randomized, and double-blind study was conducted to compare the influence on postoperative pain of equal volumes of saline, bupivacaine, or bupivacaine with adrenaline, injected both intraarticularly and into the wound puncture site, for 118 day case patients undergoing elective knee arthroscopy. Marginal analyses of postoperative visual analogue pain scores and postoperative fentanyl doses showed that the group given bupivacaine with adrenaline had less postoperative pain when compared with the saline group. However, when multifactor analyses were performed, preoperative visual analogue pain scores, operation type and length, and the sex of the patient were all shown to be significant predictors of postoperative pain, but the use of bupivacaine was not. We conclude that the observed differences in postoperative pain were due to differences between the groups in these predictive factors, especially preoperative pain scores, and that the use of bupivacaine was less important and not statistically significant in influencing postoperative pain. PMID- 8461078 TI - Arthroscopic observations before and after manipulation of frozen shoulder. AB - The purpose of this article is to report the arthroscopic findings before and immediately after manipulation for frozen shoulder. Twenty patients were selected for manipulation under general anesthesia after failing to improve with conservative measures in 6 months. The findings showed the joint capsule was difficult to penetrate with the arthroscope cannula and obturator because of the thickness of the capsular tissue. The glenohumeral joint accepted less than the normal amount of fluid. The humeral head was tight against the glenoid even in the suspended position. The main intraarticular finding was vascular synovitis. There were no intraarticular adhesions or degenerative changes. An immediate postmanipulation second-look arthroscopy showed there was synovial and capsular hemorrhage indicative of tearing from the manipulation. After glenohumeral manipulation, the joint accepted more fluid, and the humerus was easily distracted away from the glenoid with intraarticular distention. PMID- 8461079 TI - Full-thickness supraspinatus tendon tears with intact superior glenohumeral capsule. AB - Fourteen of 318 consecutive shoulder arthroscopies performed over 5 years were found to have a complete tear of the supraspinatus tendon with an intact superior glenohumeral joint capsule. All tears were surgically repaired into a bony trough in the greater tuberosity. All of these tears were found in the past 2 years, representing the last 155 arthroscopies performed. This would indicate that there were probably similar lesions that were missed in earlier cases. This represents a significant pitfall injury that may yield a negative arthrogram and may be overlooked in arthroscopic shoulder surgery unless close inspection of the bursal side of the rotator cuff is accomplished. PMID- 8461080 TI - Arthroscopic staple capsulorrhaphy: a long-term follow-up. AB - Fifty-four shoulders with recurrent anterior shoulder instability were evaluated following arthroscopic staple capsulorrhaphy. Average follow-up for those with only the index surgery was 39 months. Eighteen patients (33%) experienced at least one episode of postoperative instability. Ten underwent an open reconstructive procedure. Routine radiographs at time of follow-up demonstrated loose staples in 15% of asymptomatic patients. Range of motion was preserved following surgery. There was no loss of forward elevation. An average of 5 degrees of external rotation and one spinal segment in internal rotation were lost following surgery. Forty-three percent of overhead athletes were able to return to their preinjury level of activity. Caution should be taken when considering arthroscopic staple capsulorrhaphy as recurrence rates are higher than those following open reconstruction. However, range of motion and functional level are well-maintained. When capsulorrhaphy is performed, consideration should be given to routine staple removal following adequate capsular healing. PMID- 8461081 TI - Arthroscopic treatment of full-thickness rotator cuff tears: 2- to 7-year follow up study. AB - This study analyzes the midterm follow-up results of 40 full-thickness rotator cuff tears treated by arthroscopic subacromial decompression and debridement. Patients were selected for this prospective study based on a variety of factors, including physiologic age, handedness, activity level in occupation or avocation, and preoperative estimate of repairability. Patients were divided into three groups based on the size of the tear as measured during surgery; results were evaluated on the UCLA shoulder rating scale. This study emphasizes the importance of patient selection when applying arthroscopic treatment for full-thickness rotator cuff tears. Small (0-2 cm) tears (n = 10) in older individuals not involved in strenuous activities did well (90% satisfactory). Patients with larger (2-4 cm) repairable tears (n = 8) did poorly (50% satisfactory) in comparison with our previous study of the results of open repair (84% satisfactory). Arthroscopic treatment in patients with massive, irreparable tears (n = 22) did not restore lost strength or range of motion, but there was significant pain relief, and 86% were satisfied with the results on a limited goals basis. The study concludes that with proper patient selection, arthroscopic treatment has a valuable, but limited, role in the treatment of full-thickness rotator cuff tears. PMID- 8461082 TI - Bony anatomy of coracoacromial arch: implications for arthroscopic portal placement in the shoulder. AB - Ease of access and occasional iatrogenic damage to the shoulder during arthroscopic procedures is dependent in part on bony landmarks that are not constant in their positions. Coracoacromial arch morphology of 280 scapulae was examined to study bony variations that influence portal placement posteriorly, superiorly, anteriorly, and laterally. PMID- 8461083 TI - Endoscopic carpal tunnel release: a cadaveric study. AB - Endoscopic carpal tunnel release was performed on 13 fresh-frozen cadavers using the Agee 3-M "Inside Job" Endoscopic Carpal Tunnel Release System, by a surgeon specifically trained in the technique and with a large clinical experience. Independent dissections showed no inadvertent lacerations to nerves, vessels, or tendons. The superficial palmar arch, the communicating branch between the ulnar and median nerves at the palm, and the common digital nerves to the third and fourth web spaces were the structures most at risk. Measurements of the distances between external landmarks were not helpful in accurately predicting the depth of blade insertion. In five of 13 cases there was complete release of the transverse carpal ligament. In four of the remaining eight cases fine fibers of the transverse carpal ligament or fascia connecting the thenar and hypothenar muscles were left over. In the other four cases there was an incomplete release of the transverse carpal ligament. The palmar fascia and more volar structures were preserved in the majority of cases. PMID- 8461084 TI - Arthroscopic Herbert screw fixation of patellar osteochondritis dissecans. AB - Osteochondritis dissecans of the patella is a rare cause of anterior knee pain. The lesion is thought to arise from chronic shear stress across the patella articular surface, producing a fragment of cartilage and subchondral bone that may remain in situ or become detached. When attempts at conservative treatment fail to provide satisfactory results, operative intervention is indicated. We present the case of a symptomatic lesion of the patella treated successfully with arthroscopic internal fixation using a retrogradely directed Herbert screw. The literature is reviewed with an emphasis on pathophysiology, diagnosis, and surgical treatment. PMID- 8461085 TI - Bilaterally painful anomalous insertion of the medial meniscus in a volleyball player with Marfanoid features. AB - A female volleyball player with a Marfanoid habitus had bilateral symptomatic anomalous insertions of the medial meniscus. Arthroscopic resection of the anomalous portions of the medial menisci as they attached to the anterior cruciate ligament successfully eliminated her symptoms. PMID- 8461086 TI - Foreign body arthroscopically retrieved from the elbow. AB - A patient was found to have a tea-cup-handle fragment in her elbow joint. The fragment was removed arthroscopically. Interestingly, the patient was unaware of its presence and was asymptomatic for > 29 years. PMID- 8461087 TI - Transligamentous motor branch of the median nerve discovered during endoscopically assisted carpal tunnel release. AB - The endoscopically assisted carpal tunnel release is an alternative to open procedures. A case is presented in which a transligamentous motor branch of the median nerve exits from the main trunk in a proximal and ulnar location. It is discovered from within the carpal canal during an endoscopically assisted procedure. The authors suggest adherence to strict principles to minimize potential complications in the rare event of an anatomic anomaly. PMID- 8461088 TI - Arthroscopic assisted PCL reconstruction: a technical note on potential neurovascular injury related to drill bit configuration. AB - Neurovascular injury is a potential complication during arthroscopic assisted or open posterior cruciate ligament (PCL) reconstruction. The anatomical configuration of the posterior tibia and the square configuration of the end of commonly used drill bits require special attention. One portion of the drill bit may cut out of the tibia < or = 20 mm distal to the exit point of the guide wire. The sharp square edges of these drill bits have a greater potential to traumatize adjacent soft tissue and to increase the risk of neurovascular damage. This risk may be decreased by using a tapered drill bit, an oscillating drill, and careful elevation and retraction of the overlying soft tissue. PMID- 8461090 TI - Arthroscopic meniscus repair: the easy way. AB - A new suturing system that offers the arthroscopist the ability to perform both inside-out and outside-in techniques for repairing meniscus tears with the same instrumentation is introduced here. Depending on the location of the tears, the surgeon can use either technique; in all the cases, meniscus repair can be performed in the easiest way. PMID- 8461089 TI - Endoscopic ACL reconstruction: a technical note on tunnel length for interference fixation. AB - The total length of bone-patella tendon-bone autografts can vary significantly between individuals. Grafts that are "too long" may protrude from the tibial tunnel site, precluding interference screw fixation. A simple calculation can be used to estimate the length of the tibial tunnel required to accommodate the graft. An intraoperative final check can be made with a calibrated drill. This distance should accommodate the total graft length. If necessary, minor adjustments that include trimming the bone plugs or deepening the femoral osseous tunnel can be made to prevent graft protrusion. PMID- 8461091 TI - Surgical technique of meniscal replacement. AB - Meniscal replacement by allograft and prosthesis is under laboratory and investigational clinical practice. In order to succeed, a replacement must duplicate the exact mechanical function of the original meniscal cartilage. The technique of replacement described in this article permits minimal disruption of the joint tissues, accurate placement of the meniscal horns, and secure fixation of the meniscal synovial junction. PMID- 8461092 TI - Osteochondritis dissecans of the talus: a new technique for arthroscopic drilling. AB - Ankle arthroscopy is an effective procedure for the evaluation and management of osteochondritis dissecans of the talus. For active individuals with detached lesions, excision, curettage, and drilling are an effective treatment. The ability to drill arthroscopically significantly reduces the morbidity associated with open procedures. The use of an anterior cruciate ligament guide and the transmalleolar approach are techniques that have been advocated for the drilling of defects on the posteromedial aspect of the talar dome. However, we describe a new technique using the meniscal repair instrumentation that permits accurate arthroscopic localization and drilling of osteochondral lesions; no transmalleolar portal is required. PMID- 8461093 TI - Arthroscopic suturing of TFCC lesions. AB - Different types of triangular fibrocartilage complex (TFCC) lesions have been described. We propose an arthroscopic repair of the peripheral tear, as it is a tear in the vascular portion of the TFCC. The technique is based on one used for meniscal repairs of the knee, and it is quite easy to perform. PMID- 8461094 TI - Complications associated with the use of an infusion pump during knee arthroscopy. PMID- 8461095 TI - [Perioperative preventive use of antibiotics in large ENT tumor operations]. PMID- 8461096 TI - [A forehead light for the coat pocket]. PMID- 8461097 TI - [Difficulties in recognition and treatment of lethal midline granuloma and otolaryngologic and radiotherapeutic practice]. AB - The authors report on two cases of a "lethal midline granuloma". The first patient was treated by irradiation and chemotherapy. He lives for the last three and a half years in complete remission. The established diabetes did not affect the healing process. In the second case only a palliative irradiation was practicable because of the extreme tumour propagation, but the result was nevertheless good. PMID- 8461098 TI - [Radical parotid surgery of metastatic malignant melanoma]. AB - With an increasing incidence of the malignant melanoma we also have to expect an increasing number of metastases of the parotid lymph nodes. Up to now there are no definite guidelines concerning the surgical treatment of these metastases. What is important is the question whether the facial nerve should be resected or retained. Between 1987 and 1991 in the ENT-clinic of the University Hamburg Eppendorf eight patients were treated for metastases of a malignant melanoma in the parotid gland. The clinical course demonstrates that there is no indication for a radical surgical treatment of these patients. It neither leads to a delayed appearance of distant metastases, nor does it improve the life expectancy. PMID- 8461099 TI - [Anthracycline derivatives as photosensitizing agents in photodynamic laser therapy: an in vitro study with squamous epithelial cancer cells of the mouth cavity]. AB - Photodynamic laser therapy performed with hematoporphyrin derivatives has become increasingly important in the treatment of well-defined tumors in superficial sites. Limitations of this procedure result from the side effects of hematoporphyrin derivatives. In searching for possible alternatives to the usual photosensitizing agents, we studied the cytostatic drugs adriamycin and epirubicin. In order to evaluate the photodynamic effects of these agents we conducted in vitro studies on isolated cells from a squamous cell carcinoma of the oral cavity. The light source employed was an argon laser with wavelengths at 488/514 nm. Comparison of the cytostatic effect achieved by these anthracycline derivatives with and without laser light treatment showed a pronounced photodynamic effect. These results may herald new photodynamic therapeutic modalities. PMID- 8461100 TI - [Computerized manometry and deglutition after pharyngolaryngeal tumor resections]. AB - 33 patients were examined after laryngopharyngeal surgery by means of computer manometry using 4-channel-pressure probes. After local tumour resection in the region of tonsils and lateral oropharyngeal wall a slight cranial decrease in pressure results. Resections of the soft palate, glossotonsillar groove, base of the tongue, and of the vallecula lead to a cranial release of pressure reducing the driving force of the tongue. The swallowing action is therefore delayed and completely uncoordinated resulting in dyskinesia of the PE segment. Stenosis in the PE segment after hypopharyngeal resections increases the resistance to bolus transfer. If the base of the tongue is intact the obstruction can be compensated. After laryngectomy the sphincter pressure is decreased reducing the hypopharyngeal suction pump and prolonging bolus transfer. The tongue driving force, however, is increased. As long as the base of the tongue region is intact, pressure is not released and bolus transfer not severely impaired despite missing contraction of the pharyngeal constrictor muscle. Thus, reconstructive procedures after ablative pharyngeal surgery have to provide more "high-volume-tissue" in the base of the tongue (i.e. myocutaneous pectoral flap) in order to initiate swallowing and avoid cranial release of pressure whereas in the PE-segment more "low-volume-tissue" is necessary (i.e. myofascial pectoral flap) to facilitate bolus transfer. PMID- 8461101 TI - [Lymph node metastases of the neck in unknown primary tumor: is there a differential imaging diagnosis?]. AB - In 32 patients suffering from cervical lymph node metastases with an unknown primary tumour the pretherapeutic findings via sonography, CT and MR were compared and the post-therapy findings of tumour aftercare assessed. After an average follow-up period of 38 months the group of branchiogenic cervical cysts had no recurrence. In the group of 18 patients with more than one cervical lymph node metastasis without primary tumour, either the primary tumour or further lymph node metastases became manifest in 11 patients after an average follow-up period of 36 months. Imaging of the number of lymph node metastases and differentiation between malignant degenerated branchiogenic cysts and lymph node metastases without primary tumour is important for prognosis. A combination of findings from sonography, CT and MR enables performance of such differential diagnosis due to morphological aspects and aspects that are conditioned by the contrast medium. PMID- 8461102 TI - [The emergency: traumatic aneurysm in the area of the head-neck]. AB - Bleeding of aneurysm of cervical arteries is an emergency situation in ENT surgery. Compression of trachea and big cervical veins together with blood loss needs immediate treatment. Three cases are demonstrated presenting diagnostic and therapeutic management of one spontaneous respectively posttraumatic aneurysm of the inferior thyroid artery, and two aneurysms of lingual respectively facial artery after tonsillectomy. Interventional angiography plays an important role in overcoming such problems. Intravasal application of a platinum coil stops bleeding of the aneurysm and surgical revision of the neck can be avoided. PMID- 8461103 TI - [Subcutaneous emphysema of the neck and pneumomediastinum after arthroscopy of the knee joint. A case report ]. PMID- 8461104 TI - [Short-term changes in the larynx and voice after intubation]. AB - The endoscopic and stroboscopic picture of the larynx as well as the voice were examined pre-operatively and on the first or second post-operative day in 75 patients who had been anaesthesized with intubation. The stroboscopic findings were evaluated according to the criteria suggested by Schurenberg (1990). The quality of the voice was estimated with a voice purity index (Moser 1984) and the dynamic and frequency range of the voice was measured. After intubation, we found alterations of the mucous membrane in 73% of the patients: increased amount of visible blood vessels, bleeding into the vocal cords or the trachea, bruises at the processus vocals or the arytenoid cartilages. The stroboscopic picture showed deterioration: pre-operatively large amplitudes and/or mucosal waves became even larger postoperatively, small amplitudes and mucosal waves decreased even further. The timing and the spatial symmetry of the vocal cord movements also deteriorated. On the average, the dynamic range and the frequency range of the voice did not change. However, in individual cases the changes were considerable. The same was true for the parameters of the voice purity index. There was no statistically significant dependency on sex or age of the patients, the duration of the intubation or the diameter of the intubation tube. PMID- 8461105 TI - [Jatho stoma reconstruction--cannula-free, self-anchored tracheostomy in laryngectomy patients]. AB - Since 1987 we are using a tracheostoma construction technique proposed by Jatho in 1976. A vertical incision is made in the anterior wall of the trachea. A triangular skin flap is interdigitated into the slit. The slit is additionally held open by a thread on each side of the trachea which leads through the periods of the subclavial bone and from there through the skin. 34 patients, who were operated on according to this technique were followed up during a period between 3 and 43 months. None of them needed a cannula to keep the stoma open. Four of these patients underwent a revision procedure analogue to that one described above. These results are compared to the results from conventional stomal construction and various stoma plasty techniques found in literature. PMID- 8461106 TI - How we spent our vacation: collaborative storytelling by young and old adults. AB - Young and old dyads collaborated in describing a mutually experienced event. Three general aspects of the vacation descriptions of 10 younger (M = 28.5 years) and 10 older (M = 70.7 years) married couples were examined. First, regarding the structure of the stories, the older adults' speech contained longer clauses, and they were less likely to situate an event in absolute time than were the younger adults. Second, regarding the content of the stories, older couples' discourse was more subjective, with more descriptions of places and people and fewer descriptions of itineraries than younger couples'. Third, regarding the interactions of the collaborators, the older couples produced fewer words of support for their spouse and more monologues than did the younger couples. This pattern of findings may result from a strategy by the elderly storytellers to decrease the memory demands of the task and the cognitive demands of the collaboration. PMID- 8461107 TI - Relaxation for insomnia and hypnotic medication use in older women. AB - Relaxation therapy was given to 3 groups of older women (N = 57): (a) hypnotically medicated insomniacs, (b) nonhypnotically medicated insomniacs, and (c) noninsomniacs. Groups b and c were receiving antihypertensives. Self-reported sleep and medication data were collected for 1 week at pretreatment (except relaxation), posttreatment, and 6-weeks follow-up. Three relaxation sessions, a nondemanding, hybrid method, were administered with the rationale of helping insomnia or high blood pressure. Substantial sleep improvement occurred only for nonhypnotically medicated insomniacs. Substantial sleep medication reduction (47%) occurred only for hypnotically medicated insomniacs. This relaxation approach proved valuable, but the nature of the treatment effect was dependent on the medication status of the insomniac. PMID- 8461108 TI - The impact of differences in subordinate and supervisor age on attitudes and performance. AB - In a study of the influence of differences in employee age and the age of the employee's immediate supervisor, an age-difference variable was created and used to test 4 competing sets of predictions for performance and attitudinal outcomes within a sample of 292 high school teachers. Analyses revealed that employees who were older than their supervisors (a) reported better working relations with their supervisors, (b) evaluated their supervisors more favorably, and (c) received ratings from their supervisors that were not less favorable than other employees. The results suggest that bias does not necessarily operate against employees who are older than their supervisors and that a relational approach that is based on attribute similarity-dissimilarity offers an additional source of systematic variance that can aid in explaining individual responses. PMID- 8461109 TI - Event-related potentials as indicators of repetition priming in young and older adults: amplitude, duration, and scalp distribution. AB - Event-related brain potentials (ERPs) were recorded in young and older adults in an indirect repetition priming paradigm. Compared with the young adults, the older adults' ERP repetition effect was larger and of longer duration, due entirely to greater amplitude elicited by the repeated item. These data suggest that, although indirect memory (as indexed by a robust ERP repetition effect) appeared to be intact in the older adult, the possibility exists for qualitative age-related differences consistent with inefficient and/or additional processing of the repeated item. PMID- 8461110 TI - Caring for an institutionalized parent: the role of coping strategies. AB - This study extends knowledge about the stresses of caregiving by considering relationships between adult children and their institutionalized parents. Although previous studies have indicated that emotional strains experienced by adult children with institutionalized parents are of similar magnitude to those experienced by caregivers in the community, little attention has been paid to effects that may mediate the stressor-mental health relationship. Coping strategies were hypothesized as mediators of the stressor-mental health relationship. Data from 424 adult children with a parent living in a nursing home revealed that emotion-focused coping strategies mediate the relationship between stressors and mental health, whereas problem-focused coping strategies do not mediate this relationship. Findings emphasize the importance of examining coping strategies as multidimensional entities having differential effects on mental health. PMID- 8461111 TI - Blocks in choice responding as a function of age and physical fitness. AB - Although both physical fitness and aspects of cognitive functioning are known to be poorer among older people, there is conflicting evidence about the interaction between age and fitness. Is greater age more strongly associated with impaired cognition among less fit people than it is among more fit people? In a sample of employed men aged 17-63 years, it is shown that this interaction is significant with respect to the occurrence of exceptionally slow responses but is not significant for mean reaction time. Multiple regression analyses suggest that the former measure may be interpreted as an inability to maintain concentration over time rather than as an index of response speed. PMID- 8461112 TI - Age differences in hostility among middle-aged and older adults. AB - Multiple measures of hostility were administered to middle-aged and older volunteers. There was a positive association between age and self-report measures reflecting hostile beliefs about others, including cynicism and suspiciousness. There was a weak inverse relationship between age and self-report measures of the overt expression of anger and aggression, but no association between age and measures of covert hostility was found. There was a positive relationship between age and an assessment of hostile behavior that was based on the respondent's interaction style during an interview. The magnitude of these age trends did not differ between men (n = 50) and women (n = 75). These findings illustrate the multidimensional nature of hostility. They also have practical implications for older people because hostility is associated with psychological well-being and has been shown to have consequences for health and longevity. PMID- 8461113 TI - Why do semantic priming effects increase in old age? A meta-analysis. AB - This study reports a meta-analysis comparing the size of semantic priming effects on young and older adults' lexical decision and pronunciation latency. The analysis included 15 studies with 49 conditions varying the semantic relatedness of a prime stimulus (single word or whole sentence) and a target word. An effect size analysis on the difference between young and older adults' semantic priming effect (unrelated minus related latency) indicated that semantic priming effects are reliably larger for older than for young adults. There was no evidence for nonhomogeneity in this age difference across the different conditions. The relationship between young and older adults' semantic priming effects was described by a function with a positive intercept and a slope of 1.0. This pattern of findings favors aging models postulating process-specific slowing rather than general cognitive slowing. PMID- 8461114 TI - Age difference patterns of psychometric intelligence in adulthood: generalizability within and across ability domains. AB - Cross-sectional data from the 5th (1984) wave of the Seattle Longitudinal Study are reported with regard to the generalizability of age differences in psychometric intelligence within and across ability domains. Ss were 1,628 community-dwelling individuals drawn from a Pacific Northwest health maintenance organization. Age difference patterns of 9 groups with mean ages from 29 to 88 years are examined for the ability domains of verbal ability, spatial orientation, inductive reasoning, numeric ability, verbal memory, and perceptual speed. Each ability is marked by 3 or 4 observed variables. PMID- 8461115 TI - Orienting tasks as moderators of narrative and expository text recall in adulthood. AB - Incidental narrative and expository prose memory of 60 older adults (M = 72 years) and 60 younger adults (M = 24 years) was assessed following orienting tasks that emphasized either relational (sentence scrambling) or individual proposition (letter deletion) information or following a control condition. Orienting tasks were done capably, but older adults took longer and made more errors on the letter-deletion task than did younger adults. Age differences in recall were observed consistently for expository texts, but for narrative texts, age differences in recall were observed only when letters were deleted. If orienting tasks overtax older adults' processing resources or emphasize shallow information, recall gains may be minimal. PMID- 8461116 TI - Age differences in the performance of computer-based work. AB - This study investigated the extent to which age had an impact on the performance of computer-based work. Three simulated real-world computer-interactive tasks that varied in complexity and pacing requirements were evaluated. Ss included 65 women, ranging in age from 25 years to 70 years. The methodology encompassed physiological, subjective, and objective performance measures. The data indicated that previous computer experience and age had a significant impact on the performance of the 3 tasks. Increased age was associated with longer response times and a greater number of errors for all 3 tasks. Age also influenced perceptions of fatigue and task difficulty. The findings are discussed in terms of the implications for training and job design. PMID- 8461117 TI - Do men show more rapid age-associated decline in simulated everyday verbal memory than do women? AB - Recent magnetic resonance imaging data suggest that men show more rapid age associated atrophy of the left hemisphere than do women. To investigate whether a similar pattern occurs for functional decline, the authors tested 417 male-female pairs, ages 17-79 years and matched perfectly on age and education, on 3 computer simulated everyday verbal memory tests: Name-Face Association, First-Last Name Associate Learning, and Grocery List Selective Reminding. Age and gender significantly predicted performance on all 3 tests. By contrast, only 1 of 15 Age x Gender interactions was significant, accounting for merely 1% of the test variance. These data suggest that although gender-based differences in rate of left-hemisphere structural decline may occur with normal aging, these apparently do not translate into differential functional decline in simulated everyday verbal memory. PMID- 8461118 TI - Age and the self-perception of ability: a twin study analysis. AB - Two thousand nine hundred seventy-four adults, including 678 monozygotic and 547 dizygotic twin pairs, aged 27-86 years, self-rated ability on 6 factors: Interpersonal Competence, Workplace Skills, Trade Skills, Intellectual and Cultural, Domestic Skills, and Athletic Competition. Age accounted for no more than 2% of the variance on any factor, and, although there were significant gender effects, no significant Age X Gender interactions were observed. Twin similarity did not vary significantly with age, and biometrical variance component estimates were statistically homogeneous across age with talent factor variance being apportioned approximately equally to genetic and nonshared environmental factors. Consistent failure to find age effects as well as consistent observation of significant heritability support the conclusion that self-concept crystallizes early in adulthood and reflects genetically influenced psychological characteristics. PMID- 8461119 TI - Activity memory and aging: the role of motor retrieval and strategic processing. AB - This study examined the role of retrieval and encoding mechanisms in the magnitude of age differences in the recall of subject-performed tasks (SPTs). Eighty older (60-79 years old) and 80 younger adults (18-26 years old) were tested in 1 of 4 conditions by varying modality at both encoding and retrieval. The role of list organization in reducing age differences in SPT recall was also examined. The results suggested that older adults' SPT recall improves when motor processing is enhanced by list organization. Age differences in recall were reduced for an organized list when motor processing occurred during retrieval or encoding, but age differences in recall of an unorganized list remained under most conditions. Discrepant results in the literature concerning the magnitude of age differences in SPT recall could be due in part to differences in list characteristics, such as organization, that have not been fully explored. PMID- 8461120 TI - Age-related differences in the motoric aspects of transcription typing skill. AB - Eighty typists ranging in age from 21-71 years and in skill from 24-110 net words per minute participated in 2 experiments examining age-related differences in the motoric aspects of transcription typing skill. Age- and skill-related differences were examined for 2 simplified typing tasks: letter reaction time, which assessed latency to type a single keystroke, and digraph typing, which assessed the latencies to type 2 consecutive keystrokes. A finger tapping and choice reaction time task were also included. The results indicated that low-skill, older typists exhibited a deficit in both the translation and the execution components of motor performance, whereas high-skill, older typists exhibited a deficit in translation only. An additional task that manipulated preview of the text to be typed replicated the findings of Salthouse (1984), suggesting that older typists compensate for age-related slowing by beginning keystroke preparation sooner. PMID- 8461121 TI - Adults with Down syndrome and their aging mothers: diagnostic group differences. AB - Adults with Down syndrome (n = 160) and their aging mothers were compared with adults who have mental retardation due to other causes (n = 253) and their mothers in order to determine the nature and direction of diagnostic group differences at the middle and later stages of the family life course. Consistent with research on young families with a child who has Down syndrome, aging mothers of adults with Down syndrome reported less conflicted family environments, more satisfaction with their social supports, and less stress and burden associated with caregiving than did mothers whose adult child's mental retardation was due to other causes. Factors associated with patterns of stability and change in diagnostic group differences were discussed. PMID- 8461122 TI - Maternal reports of behavior of siblings of children with Down syndrome. AB - Mothers of children, ages 6 to 13 years, representing two target groups were interviewed: siblings of children with Down syndrome and a comparison group of siblings of children without Down syndrome. Mothers were interviewed regarding their expectations of typical child behavior, their perceptions of conduct problems of their child, and the extent to which that child shared household responsibilities. There were no significant differences between the groups regarding expectations of "typical" children, but the mothers of girls who had a sibling with Down syndrome reported significantly more conduct problems than did either mothers of children without Down syndrome or mothers of boys with a sibling who had Down syndrome. Groups did not differ with regard to the number of household tasks, but reports of conduct problems in the girls who had a sibling with Down syndrome were inversely related to the number of tasks undertaken. PMID- 8461123 TI - Type and frequency of social interaction among workers with and without mental retardation. AB - The social/verbal interactions of 6 employees with moderate or severe mental retardation and 6 workers without mental retardation were observed in six restaurants. Results showed that target workers without mental retardation gave more directions, asked more work-related questions, initiated more jokes, and had more general work-related comments than did target workers with mental retardation. The latter received more greetings and social amenities. Interactions between workers with mental retardation and the job coach correlated negatively with the workers' initiation of interactions with co-workers who did not have mental retardation. Implications for job placement and training as well as future research needs were discussed. PMID- 8461124 TI - Relation between mental age and vocabulary development among children with mild mental retardation. AB - An investigation of the relation between lexical knowledge and mental age (MA) in elementary school-age children with mild mental retardation was conducted. Lexical knowledge was assessed using the Peabody Picture Vocabulary Test-Revised (PPVT-R) and the Boehm Test of Basic Concepts. Items on the PPVT-R focus on labels for objects and events; items on the Boehm focus on relational terms. Mental age was measured via the Columbia Mental Maturity Scale. Results indicated that the relation between lexical knowledge and MA depended upon the nature of the vocabulary test: The correlation between the Boehm and MA was significantly higher than that between the PPVT-R and MA, suggesting that for this population, MA is more strongly related to knowledge of abstract relational terms than to knowledge of labels for objects and events. The latter may be more open to the influence of differential language experience. PMID- 8461125 TI - Dynamic contextual variables and the directives of persons with mental retardation. AB - We examined the ability of 14 persons with mental retardation and of 14 children without mental retardation to adjust the linguistic form of their directives as a function of their listener's affective state (happy or sad) and activity level (busy or idle). Directives were elicited by requiring the subjects to obtain toys from an adult listener. We found that both groups of subjects were sensitive to these dimensions of the communicative context. However, the directive forms used by the subjects with mental retardation were more imposing overall. PMID- 8461126 TI - Reliability of psychiatric and psychological diagnoses of mental retardation severity: judgments under naturally occurring conditions. AB - The reliability of diagnoses of mental retardation severity was examined through the comparison of psychiatric and psychological case reports found in client records. For a sample of 126 dually diagnosed clients, overall chance-corrected agreement was .47, ranging from .38 (for diagnoses of moderate mental retardation) to .55 (for diagnoses of borderline mental retardation). Results showed that the analysis of naturally occurring variation in diagnostic practices (including variability in professional judgment and assessment methods) may offer a more realistic appraisal of the reliability of diagnostic decisions in professional practice situations than do studies in which important sources of diagnostic error are controlled. PMID- 8461127 TI - Incidence of excessive/impacted cerumen in individuals with mental retardation: a longitudinal investigation. AB - A major sequelae of impacted cerumen (earwax) is conductive hearing loss, which can be deleterious to linguistic, social, and intellectual development, particularly for individuals with mental retardation. The longitudinal incidence (12-year period) of excessive/impacted cerumen and related conductive hearing loss of 117 adults with mental retardation was examined. Results indicated a considerably higher incidence of excessive cerumen and cerumen impaction with associated conductive hearing loss in adults with mental retardation (28%) than in the general adult population (2% to 6%). Moreover, a strong propensity for recurrent cerumen impaction in the mentally retarded population was found. These findings were discussed in view of the management of cerumen impaction among individuals with mental retardation. PMID- 8461128 TI - Impact of community-based instruction on the development of adaptive behavior of secondary-level students with mental retardation. AB - The impact of community-based instruction on the development of adaptive behavior in 34 high school students with moderate to profound mental retardation was examined. Results were: (a) Students made statistically significant gains in three of four domains of the Scales of Independent Behavior; (b) student IQ, level of student ambulation, and presence of behavior problems were not significant predictors of the amount of community-based instruction students received; and (c) the amount of community-based instruction was a more powerful predictor of gains in these domains than were IQ, level of student ambulation, and the presence of behavior problems. Results were discussed in terms of implications for the design and implementation of secondary programs for students with mental retardation. PMID- 8461129 TI - Determining the prevalence of human immunodeficiency virus (HIV) within a residential facility for persons with mental retardation. AB - Administrators of residential facilities for persons with mental retardation must take a proactive stance in determining the prevalence of HIV in the population. Administrators of the Stockley Center, a 345-bed ICF/MR, approached the issue utilizing a double-blinded seroprevalence study. Their aim was to use results from this testing to identify settings of high to moderate prevalence for purposes of reducing the further spread of infection. PMID- 8461130 TI - The neurofibromatosis type 1 gene and its protein product, neurofibromin. PMID- 8461131 TI - Guidance and topographic stabilization of nasal chick retinal axons on target derived components in vitro. AB - We studied mechanisms underlying the generation of topographic order within the developing chick retinotectal connection by combining the recently introduced stripe assay with a novel membrane protein fractionation technique. Our experiments show a preference of temporal and nasal retinal fibers for growing on cell membranes prepared from their proper target area. In addition, membrane preparations from posterior tectum were found to prolong substantially the survival of nasal neurites in vitro. We conclude that tropic as well as trophic interactions contribute to the generation of topographic maps during embryogenesis, in our case to the homing of nasal axons within the posterior tectum. PMID- 8461133 TI - hikaru genki, a CNS-specific gene identified by abnormal locomotion in Drosophila, encodes a novel type of protein. AB - We have identified a gene, hikaru genki (hig), whose mutant phenotype includes abnormal locomotor behavior. Mutant first instar larvae have uncoordinated movements, and both larvae and adults have reduced locomotion. Sequence analyses revealed that this gene encodes a novel type of protein with a signal sequence, but without transmembrane regions. One of its domains has similarities with immunoglobulin domains; three or four regions are similar to a complement-binding domain found in complement-related proteins and selectins. In situ hybridization to embryos revealed that accumulation of the hig transcripts is restricted to subsets of cells in the CNS. Our data suggest that hig has a role in the development of CNS functions involved in locomotor activity. PMID- 8461132 TI - Evidence that fibroblast growth factor 5 is a major muscle-derived survival factor for cultured spinal motoneurons. AB - We examined the potential role of fibroblast growth factor 5 (FGF-5) as a target derived trophic factor for spinal motoneurons. Northern analysis of total RNA from rat skeletal muscle revealed an FGF-5 mRNA transcript both during the period of embryonic motoneuron death and in the adult. Recombinant human FGF-5 supported the survival of highly enriched cultures of embryonic chick motoneurons. Significant proportions of the motoneuron survival activity of rat skeletal muscle extracts could be immunoprecipitated using an antiserum to FGF-5. The immunoprecipitable activity was present in soluble and matrix-bound forms in embryonic muscle, but bound exclusively to the extracellular matrix in adult muscle. These results, along with the secretory nature of FGF-5, suggest that FGF 5 may act as a target-derived trophic factor for motoneurons. PMID- 8461134 TI - Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. AB - We performed a large-scale screen for mutations that affect the development of CNS axon pathways in the Drosophila embryo. We screened embryos from over 13,500 balanced lines and saved over 250 mutant lines whose phenotypes suggest possible defects in growth cone guidance. Here we focus on two new genes: commissureless (comm) and roundabout (robo). Mutations in comm lead to an absence of nearly all CNS axon commissures, such that growth cones that normally project across the midline instead now extend only on their own side. Mutations in robo lead to the opposite misrouting, such that some growth cones that normally extend only on their own side instead now project across the midline. The phenotypes of these two genes suggest that they may encode components of attractive and repulsive signaling systems at the midline that either guide growth cones across the midline or keep them on their own side. PMID- 8461135 TI - Neurons assemble acetylcholine receptors with as many as three kinds of subunits while maintaining subunit segregation among receptor subtypes. AB - A family of genes encoding neuronal acetylcholine receptor (AChR) subunits has been identified and cloned from vertebrates. Expression studies have implied that as few as one or two kinds of subunits may be sufficient to construct neuronal AChRs and that multiple pair-wise combinations of the gene products are capable of generating functional receptors. We show here that a class of AChRs with a predominantly synaptic location on neurons contains receptors having at least three types of subunits and that the subunits are encoded by the alpha 3, beta 4, and alpha 5 AChR genes. In addition, we show that a class of extrasynaptic AChRs on the same neurons contains the alpha 7 subunits but lacks the alpha 3, beta 4, and alpha 5 subunits. The results demonstrate that native AChRs on neurons are more complex in composition than previously appreciated and suggest that constraints on subunit interactions limit the kinds of receptor species produced. PMID- 8461136 TI - Release of LHRH is linearly related to the time integral of presynaptic Ca2+ elevation above a threshold level in bullfrog sympathetic ganglia. AB - To study the Ca2+ dependency of luteinizing hormone-releasing hormone (LHRH) release in the bullfrog sympathetic ganglia, a method was developed to fill the preganglionic nerve terminal boutons with membrane-impermeant fura-2. We found that as stimulation frequency increased from 0.5 to 40 Hz, the peak [Ca2+]i ([Ca2+]p) and the rate of rise in [Ca2+]i increased, the decay of [Ca2+]i transients followed up to three exponentials, and release of LHRH was linearly related to integral of ([Ca2+]i--[Ca2+]t)dt. The threshold level of [Ca2+]i for LHRH release for a given set of boutons on a C cell, [Ca2+]t, was estimated by the [Ca2+]p evoked by 0.5 Hz stimulation that does not induce LHRH release. PMID- 8461137 TI - Multiple promoters direct tissue-specific expression of the rat BDNF gene. AB - Brain-derived neurotrophic factor (BDNF) supports the survival of a specific set of neurons in the vertebrate nervous system. Here we show that the rat BDNF gene consists of four short 5' exons and one 3' exon encoding the mature BDNF protein. Eight different BDNF mRNAs with four different 5' ends and two alternative polyadenylation sites are transcribed from this gene. BDNF mRNAs containing exons I, II, and III are expressed predominantly in the brain, whereas exon IV transcripts predominate in the lung and heart. mRNAs containing exons I, II, and III increase markedly in the brain after kainic acid-induced seizures, whereas exon IV mRNA increases only slightly. Several transcription initiation sites were mapped upstream of the four 5' exons, and transfection of promoter-reporter gene constructs confirmed that these sequences act as promoters. Combined, the data demonstrate that alternative usage of four promoters within the BDNF gene and differential splicing control tissue-specific and seizure-induced expression of BDNF mRNA. PMID- 8461139 TI - The effect of recoverin-like calcium-binding proteins on the photoresponse of retinal rods. AB - The rod photoresponse is triggered by an enzyme cascade that stimulates cGMP hydrolysis. The resulting fall in cGMP leads to a decrease in Ca2+, which promotes photoresponse recovery by activating guanylate cyclase, causing cGMP resynthesis. In vitro biochemical studies suggest that Ca2+ activation of guanylate cyclase is medicated by recoverin, a 26 kd Ca(2+)-binding protein. To evaluate this, exogenous bovine recoverin and two other homologous Ca(2+)-binding proteins from chicken and Gecko retina were dialyzed into functionally intact Gecko rods using whole-cell recording. All three proteins prolonged the rising phase of the photoresponse without affecting the kinetics of response recovery. These results suggest that recoverin-like proteins affect termination of the transduction cascade, rather than mediate Ca(2+)-sensitive activation of guanylate cyclase. PMID- 8461138 TI - The 87K postsynaptic membrane protein from Torpedo is a protein-tyrosine kinase substrate homologous to dystrophin. AB - Postsynaptic peripheral membrane proteins at the neuromuscular junction have been proposed to participate in the immobilization of the nicotinic acetylcholine receptor at the synapse. An 87 kd cytoplasmic peripheral membrane protein has been demonstrated to colocalize with the nicotinic acetylcholine receptor in the Torpedo electric organ and at the mammalian neuromuscular junction. We have cloned the cDNA encoding the 87K protein from Torpedo electric organ, and the predicted protein sequence is homologous to the C-terminal domains of dystrophin, the protein product of the Duchenne muscular dystrophy gene. The 87K protein displays a restricted pattern of expression detected only in electric organ, brain, and skeletal muscle. Analysis of the in vitro and in vivo phosphorylation of the 87K protein indicates that it is multiply phosphorylated on serine, threonine, and tyrosine residues. The 87K protein is in a complex with other proteins associated with the postsynaptic membrane, including dystrophin and a 58 kd protein. These results suggest that the 87K protein is involved in the formation and stability of synapses and is regulated by protein phosphorylation. PMID- 8461141 TI - A novel tetrodotoxin-insensitive, slow sodium current in striatal and hippocampal neurons. AB - Slow inward currents modulate neuronal firing patterns and may generate depolarizing afterpotentials (DAPs). We report a novel, slow Na+ current (INaS) in striatal and hippocampal neurons that can generate DAPs. INaS activated at depolarizations greater than -40 mV, was tetrodotoxin insensitive, and activated and deactivated slowly over hundreds of milliseconds. INaS was dependent upon extracellular Na+, but was not affected by 0 mM extracellular Ca2+ or by Ca2+ channel blockers (Mn2+, Cd2+, or Co2+). A tetrodotoxin-insensitive, Na(+) dependent plateau potential that was likely generated by INaS was shown to underlie DAPs during intracellular recordings from hippocampal CA1 pyramidal neurons. Membrane depolarizations and DAPs generated by INaS may contribute to alterations in neuronal firing and epileptiform bursting. PMID- 8461140 TI - The internal quaternary ammonium receptor site of Shaker potassium channels. AB - Quaternary ammonium (QA) compounds inhibit K+ conductance by entering and occluding the open pore of voltage-activated K+ channels. We characterized the effects of a series of alkyl-triethylammonium blockers on the Shaker K+ channel and tested them on a series of site-directed mutants of the channel protein in order to define the structural features of the binding sites. We found that mutations in two regions of the channel protein, the pore (P) region and the last transmembrane sequence (S6), appear to alter QA binding, not through their effects on gating but perhaps through direct effects on the binding site. Several mutations in the P region affect tetraethylammonium binding but have minimal effects on longer blockers, suggesting that the hydrophobic tail contributes to binding in a nonadditive fashion. Binding of the longer blockers can be affected by varying the hydrophobicity of 1 residue within S6 by site-specific substitution, in a manner consistent with a direct hydrophobic interaction between the side chain at this site and the alkyl chains of the blocker. PMID- 8461142 TI - Long-term potentiation in the hippocampus induced by platelet-activating factor. AB - Platelet-activating factor (PAF) is an ether phospholipid that serves as an autacoid in a wide range of biological processes. We found that when PAF was added to hippocampal slices, it induced a stable and concentration-dependent increase in excitatory postsynaptic potential and population spike recordings (long-term potentiation [LTP]). The PAF effect was blocked by the PAF receptor antagonists BN 52021 and WEB 2086 and the N-methyl-D-aspartate receptor antagonists MK 801 and 2-amino-5-phosphonovalerate. However, these PAF receptor antagonists did not block LTP induced by high frequency stimulation. The facilitation induced by PAF could not be reversed by PAF receptor antagonists. Induction of either PAF-or tetanus-triggered facilitation occluded the subsequent expression of the other, suggesting a common pathway. LTP is a type of synaptic plasticity associated with the formation of memory, and PAF may play an important modulatory role in this process. PMID- 8461143 TI - Surgical treatment of congenital bronchopulmonary disease in children. AB - From 1987 to 1992, 22 children (age 0 days-14 years) were operated for congenital bronchopulmonary disease. One patient had a hamartoma. Four children had a bronchogenic cyst, in 1 patient combined with an esophageal duplication. Intrapulmonary sequestration was diagnosed in 3 children; one of whom had an esophageal duplication as well. Four children had localized emphysema. In 1 patient histology showed rhabdomyosarcoma. A lobectomy was performed following chemotherapy but recurrence was not resectable at a third thoracotomy. Ten patients had cystic adenomatoid malformation, 6 were dependent on artificial ventilation before surgery. Three patients with cystic adenomatoid malformation died in hospital: 2 after pneumonectomy who were shown to have bilateral disease and 1 died after bilobectomy and was shown to have a hypoplastic contralateral lung. Hospital morbidity involved 1 patient with recurrent pneumothorax, 2 with atelectasis of the operated lung and 3 with prolonged artificial ventilation. Late mortality involved 1 patient due to pulmonary rhabdomyosarcoma. After 1-26 months of follow-up there were no late complications. Adequate multidisciplinary treatment allows acceptable mortality and low morbidity in surgery for congenital bronchopulmonary disease in children. PMID- 8461145 TI - Diffuse subaortic stenosis: modified Konno procedures with aortic valve preservation. AB - The Konno procedure provides adequate relief of diffuse subaortic stenosis but requires aortic valve replacement. This may be questionable in patients without aortic valve lesions. Eleven patients had diffuse subaortic stenosis and normal aortic orifice: tunnel subaortic stenosis (6 patients) or diffuse hypertrophic obstructive cardiomyopathy (5 patients). The mean age was 16 +/- 14 years (range: 3 months to 45 years). The mean subaortic gradient was 95 +/- 24 mmHg (range: 60 to 150 mmHg). Two patients had previously undergone resection of discrete subaortic stenosis. Modified Konno procedures were used: aortoseptal approach with aortic annulus division in 5 patients, conal enlargement without aortic annulus division in 6 patients. There was one early death (9%, 70% CL = 1%-27%) and no late deaths. Reoperation was required in two patients: one early for iatrogenic aortic regurgitation and one late for residual ventricular septal defect and mitral regurgitation. The mean follow-up was 3.8 +/- 4.2 years (range: 2 months to 10 years). The survivors were in functional class I (8/10), had a normal left ventricular function (9/10), were in sinus rhythm (10/10) and had left ventricular outflow tract gradients ranging up to 25 mmHg (mean = 6 +/- 10 mmHg). Residual surgery-related defects included ventricular septal defect (one) and aortic regurgitation (one). In patients with diffuse subaortic stenosis and normal aortic orifice, modified Konno procedures with aortic valve preservation are preferable, effective and can be safely performed in infants and children. PMID- 8461150 TI - Mediastinal cystic hygroma: report of a case with review of the literature. AB - Cystic hygroma is a developmental malformation of the lymphatic system. It is very uncommon for this type of tumor to arise from and grow exclusively in the mediastinum. Enlargement of such a lesion within this region often produces alarming respiratory symptoms requiring immediate medical attention. PMID- 8461149 TI - Unusual variant of pulmonary arteriovenous communication. AB - We report a case of direct communication of right pulmonary artery to left atrium , a very rare congenital anomaly treated surgically with complete success at our centre. PMID- 8461147 TI - Retrograde ascending aortic dissection: a diagnostic and therapeutic challenge. AB - Aortic dissection with an entrance tear in the transverse aorta is generally considered to have the highest acute fatality rate of any type of dissection and the direction of its extension is the most difficult to predict. In a prospective study, we evaluated 61 consecutive patients (mean age 56.7 years, ranging from 21 to 75 years), presenting with ascending aortic dissection during a 36-month period and tried to clarify the incidence of retrograde ascending aortic dissection. In 49 patients (80.3%), the intimal tear was located in the ascending aorta, whereas the dissection originated in the transverse aorta in 12 patients (19.7%); in this latter group, extension was strictly retrograde in 5 patients and in both directions in 7 patients. Three patients died before operation; 58 patients underwent aortic replacement/repair under moderate hypothermia; if the primary tear extended into the transverse aorta or was not found in the ascending aorta, the aortic arch was explored during a brief period of deep hypothermic circulatory arrest. The overall operative mortality was 12.1% (7/58); it was 10.4% (5/48) in ascending aortic dissection and 20% (2/10) in dissection of the transverse aorta. Age (P < 0.005), concomitant coronary artery disease (P < 0.01) and the site of intimal tear (P < 0.01) were significant predictive factors of operative risk. A tear in the transverse aorta is almost always associated with retrograde dissection and may simulate dissection with the entrance tear in the ascending aorta. Localization of the entrance tear remains a diagnostic challenge in aortic dissection but Doppler-echocardiography had a high sensitivity in this series (96.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461148 TI - Risk factors of septicemia and perioperative myocardial infarction in a cohort of patients supported with intra-aortic balloon pump (IABP) in the course of open heart surgery. AB - In 1325 open heart operated (OHO) patients with a perioperative mortality of 5.8% the incidence of septicemia and perioperative myocardial infarction (PMI) were much higher in a cohort of 110 patients given intra-aortic balloon pump (IABP) support during the operative course. Analysis of this cohort showed that peri/postoperative insertion of the pump, the presence of disease in the descending branch of left coronary artery (LAD) and the need of more than one saphenous vein graft were risk factors for PMI. The presence of LAD disease was the only independent risk factor for PMI with an odds ratio (OR) of 4.62. Well known risk factors such as NYHA functional class, emergency, low left ventricular ejection fraction (EF) or elevated end diastolic pressure (EDP) were not prognostic of PMI. Thus, the intraoperative seemed to be more important than the preoperative risk profile for the development of PMI. Independent risk factors for the development of septicemia were the duration of IABP with an OR of 1.5 for each pump day and implantation of a valve prosthesis with an OR of 6.3. To avoid septic complications, this study suggests pump removal as soon as possible. PMID- 8461146 TI - Contractile and vascular consequences of blood versus crystalloid cardioplegia in the isolated blood-perfused rat heart. AB - The protective effects of sanguineous and asanguineous St. Thomas' cardioplegia (SCP and ACP) on post-ischemic vasodilator responsiveness, left ventricular developed pressure and end-diastolic pressure (LVDP and LVEDP), tissue adenosine triphosphate (ATP) and creatine phosphate (CP) contents were compared in the isolated blood-perfused rat heart. Five groups of hearts were studied: the controls (n = 8) perfused with blood (from a support rat) for 50 min (37 degrees C), versus hearts (n = 14/group) arrested by a single infusion of either cardioplegic solution (15 degrees C) prior to global ischemia (15 degrees C) and blood reperfusion (37 degrees C). After 2 or 4 h of ischemia and 50 min of reperfusion, endothelium-dependent vasodilator acetylcholine (1 microgram) induced a 10 +/- 0.5 and 8.5 +/- 0.5% reduction, respectively, in coronary resistance, in the SCP groups, but only a 6.5 +/- 0.6 and 4.5 +/- 0.5% reduction (P < 0.05), respectively, in the ACP groups. However, there were no significant differences in LVDP, LVEDP, tissue ATP and CP contents, and endothelium independent vasodilator response to nitroglycerin between the two cardioplegic groups. In a further study, rat hearts (n = 8/group) were arrested with SCP (magnesium concentration < 0.5, 5.0 or 16.0 mmol/l, in groups 1, 2 and 3) and subjected to 4 h of global ischemia (15 degrees C) followed by 50 min of blood reperfusion (37 degrees C). At the end of reperfusion, LVDP (at a ventricular volume of 180 microliters) was 60 +/- 3.4, 72 +/- 3.5 and 70 +/- 3.2 in groups 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461151 TI - Mitral balloon valvotomy eight years later. PMID- 8461144 TI - Adenocarcinoma and Barrett's oesophagus. A clinico-pathological study. AB - A clinico-pathological study was carried out in two series of patients in order to determine: the prevalence of adenocarcinoma in Barrett's oesophagus in patients undergoing surgical resection for columnar cancer of the oesophagus, the incidence of Barrett's oesophagus in patients with complications of gastro oesophageal reflux, and the subsequent cancer development in 3-20 years follow-up of such patients, compared with others who had no Barrett's oesophagus. Group 1 consisted of 264 patients with adenocarcinoma of the oesophagus undergoing resection and reconstruction; 18 (6.8%) had concomitant carcinoma and Barrett's oesophagus. These were predominantly male (male/female ratio 8/1) and had worse long-term survival than the other adenocarcinomas. Group 2 consisted of 782 patients with complications of gastro-oesophageal reflux, 26 (3.3%) of whom were found to have Barrett's oesophagus. When followed up for a period of up to 20 years, 4 (15.4%) of these developed cancer in the mean period of 11.5 years (1 case per 74 person-years). This is highly significant compared with 4 others (0.5%) who developed cancer amongst the 756 remaining patients in group 2 with no Barrett's oesophagus, in the mean interval of 8 years 2 months (1 case per over 1500 person-years). Of the 18 patients with Barrett's stricture, 4 (22%) developed cancer at a mean interval of 11.5 years representing one case per 51.7 person-years indicating a higher risk of cancer development in patients with Barrett's stricture compared with other patients with complications of gastro oesophageal reflux with/without columnar epithelial-lined oesophagus and no stricture. Anti-reflux operation has not protected our patients with Barrett's oesophagus against cancer development. PMID- 8461152 TI - [Prognosis in unstable angina as a function of the clinical presentation]. AB - OBJECTIVE: To assess the prognosis of Unstable Angina according to its clinical presentation using Braunwald's Classification. DESIGN: Retrospective study of hospital admissions from January 1982 to September 1990. SETTING: Coronary Care Unit and a Cardiology Department of a Central Hospital. PATIENTS: There were 132 patients, 109 men and 23 women, with a mean age of 56 +/- 9 years, all submitted to cardiac catheterization at least 90 days after hospital admission followed up during 34.2 +/- 24.2 months. MATERIAL AND METHODS: Patients were divided in three groups according to the clinical presentation of Unstable Angina: Group A- Aggravated Chronic Angina and/or "De Novo" Angina; Group B--Angina at Rest but not in the last 48 hours, and Group C--Angina at Rest in the last 48 hours. Group A was also sub-divided, and the patients with Unstable Angina after myocardial infarction were excluded. The previous clinical profile was evaluated as well as the circumstances in which Unstable Angina occurred, need of Coronary Care Unit, angiographic findings and follow-up. RESULTS: Within the 132 patients, 86 were in the group A, (59 with Aggravated Angina and 27 with "De Novo" Angina), 11 in group B, and 35 in group C. The group with Aggravated Angina had higher incidence of previous myocardial infarction and bypass surgery (p < 0.01 and p = 0.05), compared to group with "De Novo" Angina and B, and also three vessels disease associated to ventricular dysfunction. "Culprit Lesion" appeared more frequently as eccentric type I in group A, and as concentric in group C. Revascularization procedures were performed in 95 patients (CABG in 66 and PTCA in 29) being respectively: 21 and 6 were urgent, 19 and 18 were elective and 26 and 5 were late procedures. CABG were more frequent in group A. There were 73 major cardiac events in 44 patients (8 deaths, 12 myocardial infarction and 53 new episodes of Unstable Angina), which were more frequent in group with Aggravated Angina and group C. The chance of patients with major cardiac events was in a 78 months follow-up, about 25% for group with "De Novo" Angina, 50% for patients with Aggravated Chronic Angina, and was greater than 75% in patients with Angina at Rest and episodes in the last 48 hours (p < 0.05)--Log-rank Test. The worse prognosis was seen in patients with Aggravated Chronic Angina, when a gathering of clinic patterns of Braunwald's classification were present. CONCLUSIONS: In summary, the group with Aggravated Angina and group C had more severe disease, required more urgent CABG and PTCA, and had also a higher incidence of cardiac events. The group with better prognosis was the group with "De Novo" Angina, which should be distinguished of the group with Aggravated Angina who was the worst prognosis. PMID- 8461153 TI - [Automatic measurement of arterial pressure]. AB - Whenever we have a new technique for the measurement of Blood Pressure (BP), variations to standard devices should be expected. Recent guidelines for measurement and validation of automatic devices by Scientific Societies should be followed if doctors want to improve the accuracy of readings, avoiding mistakes in the diagnosis and monitoring of hypertension. To characterize the variability and reproducibility of the DINAMAP (Dynamic Automatic Mean Arterial Pressure), a random comparison with two observers (A; B) between this device and the sphygmomanometer was performed in a group of 80 patients with different pathologies. To evaluate the variability and reproducibility in the same person we analysed as well the mean variation in a setting of successive readings in 3 persons. The global correlation was good for both systolic (r = 0.9) and diastolic pressures. The behaviour of the DINAMAP for different pressure levels was obtained by the regression analyses of the pressures differences between both devices. The best correlation is found around the 140 mmHg measurements, pressures above or under this level are respectively underestimated and undervalued. We discuss the needs of a standard statistical methodology with physiological meaning for the analysis which enables to understand the multiple variations that doctors can find when performing the comparison tests. PMID- 8461154 TI - [Echocardiographic evaluation of pulmonary valve stenosis for valvuloplasty in children and adults]. AB - OBJECTIVES: 1--To determine the accuracy of the echocardiographic selection and characterization of the pulmonary stenosis (PS) for balloon valvuloplasty; 2--To analyze the differences between children and adults in obtaining the echocardiographic parameters used for pulmonary stenosis characterization. MATERIAL AND METHODS: We studied 53 consecutive patients with PS and a peak Doppler gradient > or = 40 mmHg, submitted to cardiac catheterization to perform balloon valvuloplasty if the right ventricle to pulmonary artery peak-to-peak systolic pressure gradient was > or = 40 mmHg. The patients were divided into 3 groups on the basis of age: < or = 5 years (group 1; n = 18), 6-16 years (group 2; n = 17) and > 16 years (group 3; n = 18). A complete echocardiographic study was performed including identification of valvular morphology (commissural fusion, dysplasia or mixed), determination of right ventricle to pulmonary artery peak Doppler gradient and the transducer position that yielded the highest transvalvular flow velocity (V), evaluation of the right ventricular outflow tract morphology and measurement of the valvular annulus diameter. RESULTS: Technically adequate recordings were obtained in all patients. Fifty patients (94%) were submitted to pulmonary valvuloplasty. The echo-Doppler recording of V was obtained from the parasternal position in 27 patients (51%), suprasternal in 14 (26%), subcostal in 10 (19%) and apical in 2. In group 1, the V was obtained from the suprasternal position in 8 patients (44%), subcostal in 5 (28%), parasternal in 4 (22%) and apical in 1. In group 2, it was the parasternal position in 8 patients (47%), suprasternal in 6 (35%), subcostal in 2 (12%) and apical in 1. In group 3, it was the parasternal position in 15 patients (83%) and subcostal in 3. The peak Doppler gradient ranged from 40 to 215 mmHg (mean +/- SD = 78 +/- 37) and the peak-to-peak gradient at cardiac catheterization from 32 to 220 mmHg (mean +/- SD = 81 +/- 41). The correlation between eco-Doppler peak gradient and peak-to-peak gradient at cardiac catheterization was r = 0.95 (SEE = 12 mmHg) being, for group 1, r = 0.89 (SEE = 14 mmHg), for group 2, r = 0.97 (SEE = 8 mmHg) and, for group 3, r = 0.98 (SEE = 10 mmHg). The right ventricular outflow tract shows dynamic reaction 48 patients. Two patients had an infundibular gradient > 25 mmHg, significantly underestimated by echo-Doppler in one. All 5 patients (9%) but one with angiographic criteria for valvular dysplasia, were identified by echocardiography. One patient had a mixed form. The remaining 47 patients had valvular commissural fusion. The annulus size measured by echocardiography ranged from 10 to 28 mm (mean +/- SD = 17.7 +/- 4.3) and by angiography from 10 to 28 mm (mean +/- SD = 17.6 +/- 4.4). Close correlations were found between echocardiographic and angiographic measurements: r = 0.97 (SEE = 1.1 mm) being, for group 1, r = 0.90 (SEE = 1.1 mm), for group 2, r = 0.94 (SEE = 0.8 mm) and, for group 3, r = 0.87 (SEE = 1.3 mm). CONCLUSION: The echocardiographic examination allows an accurate selection and characterization of the PS for balloon valvuloplasty. The most significant difference in the study of PS in children and adults, was the lack in the ability of the eco-Doppler to record the V from the suprasternal position in adults. 2D echocardiography can reliably measure the annulus diameter in children and adults, providing precise information for balloon diameter selection before valvuloplasty. PMID- 8461155 TI - [Diagnostic value of transesophageal echocardiography in the study of mitral prosthesis dysfunctions]. AB - The aim of this study are to establish the value of transesophageal echocardiography (TEE) in the diagnosis of mitral prostheses dysfunctions and to compare the performance of TEE and the transthoracic approach (TTE) in this context. From October 1990, the data when we started transesophageal ultrasound, till January 1992, we performed 218 TEE's. In 61 patients (pts) there was clinical suspicion of mitral prostheses dysfunction and TEE detected abnormal prostheses function in 22 pts (36%), 12 of which have been reoperated. In this group of 12 pts who underwent surgery, the basis for this study, the results of ETT and TEE were compared with surgeon's information. TEE confirmed the surgical findings in 11 patients (97%) with only one falsely positive (3%). On the other hand, TTE confirmed the surgical findings in only 6 pts (50%), confirmed partially in 3 (25%) and was falsely negative in 3 pts (25%). From these results the authors conclude: in the group of patients with mitral prostheses device dysfunction, that have been submitted to surgical treatment, there is great concordance between surgeon's findings and TEE information. TEE seems to be more accurate than TTE in the diagnosis of mitral prostheses dysfunction. Finally, TEE in conjunction with TTE is highly reliable in the diagnosis of mitral prostheses dysfunctions and spares patients from catheterism. PMID- 8461156 TI - [Torsades de pointes: analysis of 105 episodes]. AB - PURPOSE: To analyze episodes of Torsades de Pointes (TP), in search of its electrocardiographic characteristics. PATIENTS AND METHODS: We analyzed 105 episodes of TP, in 4 patients using quinidine and diuretics, recorded by 24-hour Holter monitoring. The following parameters were studied; ventricular repolarization out of TP, rhythm disturbances before TP; ECG characteristics of the onset, the bouts and the end of the TP. RESULTS: Ventricular repolarization, out of the TP, was abnormal, with the presence of U-waves at the end of the T waves, resulting in prolongation of the QT (QU) interval. The U-wave voltage was noted to be cycle-length dependent. Ventricular bigeminy preceded TP in 100 episodes (95%) and the mean interval between both parameters was 18 +/- 16 min. The onset of the TP episodes showed the "short/long/short cycle rule", hereby called "pre-pause cycle", "preparing cycle" and "trigger cycle" respectively. The rotatory QRS-T morphology around the baseline, was seen in 75% of episodes, at the beginning or throughout the bout. Monomorphic ventricular tachycardia pattern was seen in the other 25% of episodes. Termination of bouts was sudden in all cases, and persistent ventricular bigeminy led to another bout in 90 episodes (85%). CONCLUSION: In TP patients, there is enlargement of QT intervals mostly due to U-waves appearance. The U-waves seen in these cases, probably have an important role in the genesis of TP and are probably related to ventricular after potentials (triggered activity). Ventricular bigeminy is a premonitory sign of TP in patients using class 1A antiarrhythmic drugs. Persistent ventricular bigeminy post-TP episodes is a strong indicator of another bout of TP. The onset of TP is more important than its morphology for the correct diagnosis of this arrhythmia. PMID- 8461157 TI - [Diastolic intraventricular gradient detected with Doppler echocardiography in hypertrophic cardiomyopathy. Report of a case]. AB - It has recently been reported the rare existence of intraventricular diastolic gradients in patients with hypertrophic cardiomyopathy. This proves the great disturbance of diastolic function that exists in these patients. We report the case of a patient with this disease, in whom a significant diastolic intraventricular gradient was detected with color Doppler echocardiography. In the end we make a summing up of its most probable physiopathology. PMID- 8461158 TI - [Contribution of Holter monitoring in the diagnosis of a case of Prinzmetal's angina]. AB - Prinzmetal angina is a peculiar kind of angina pectoris, in which Holter monitoring has been particularly useful for diagnosis. In this paper it is reported a 56 years old male patient with coronary artery spasm induced during coronary arteriography in which the Holter electrocardiography was of most importance for decision making. PMID- 8461159 TI - [Localization of immunoglobulins in the central nervous system]. AB - The affinity of IgG to the central nervous system has been demonstrated by several authorities. The present study revealed the physiological localization of immunoglobulins. Developing human brains were obtained from autopsies, and the regional localization of IgG, IgA and IgM was examined as a function of age. Thirteen brains from children, aged 3 months to 13 years, were evaluated for IgG localization. Four other cases, aged 3 to 7 months, were stained for IgG subclasses, IgA and IgM. Positive IgG staining was observed in neurons and glial cells of the cerebrum and Purkinje cells of the cerebellum in 5 cases, aged 3 to 7 months. It was decreased in 4 cases aged 1 year (3/4 in the nerve cells of the hippocampus and Purkinje cells, 2/4 in those of the amygdala and parietal cortex, and 1/4 in other regions). IgG was absent except in the Purkinje cells of four cases, aged 3 to 13 years. Every IgG subclass and IgA existed in neurons and glial cells of the cerebrum and Purkinje cells of the cerebellum in all cases. IgM staining, however, was negative in the nerve cells of the cerebral cortex although it was positive in Purkinje cells of the cerebellum and basal ganglia. These findings suggest that the immunoglobulins possibly passed through the premature blood-brain barrier in infants, were taken up by the nerve and glial cells in the cerebral cortex and other deep structures of the central nervous system, and may exert some effects on the developing process of the brain. PMID- 8461160 TI - [Common viral infections and pediatric neurological disorders: introductory remarks]. AB - The analytical methods of nucleic acids are excellent tools to find virus antigens in various tissues, such as CSF, blood and brain; polymerase chain reaction (PCR), restriction fragment length polymorphisms (RFLP) and hybridization techniques. Antigens can be isolated from cellular and/or supernatant fractions of the CSF of patients with common viral infections. The latter means the possible infection of virus in the nervous system, however, the former depends on the species of isolated cells. If the infected cells are the brain cells and/or endothelial cells of the ventricular system, viral infection in the nervous system is inferred. On the contrary, if they are blood cells, macrophages or monocytes, further studies of EGG, cytokine assay and other clinical and laboratory tests are necessary for the diagnosis of the nervous system infections. PMID- 8461161 TI - [Herpes simplex encephalitis]. AB - Herpes simplex encephalitis (HSE) is a severe disease with high mortality and morbidity. As effective antiviral therapy improves the outcome of younger patients, the early diagnosis of the disease has become important, especially in children. The annual incidence of HSE in Japan among children is estimated to be about 100-200 cases, and the mortality is 10-20%. Instead of brain biopsy, we applied the polymerase chain reaction (PCR) assay to the early diagnosis. The DNA of herpes simplex virus was detectable in CSF of all HSE patients in the acute phase. Serial quantitation of viral genome by PCR also revealed that the amount of DNA decreased gradually corresponding to antiviral therapy, and it turned to be negative 3 to 18 days after the onset of neurological signs and symptoms (mean 10.1 days). These results show the PCR assay is a useful diagnostic tool for the early and non-invasive diagnosis of HSE. PMID- 8461162 TI - [Neurological complications of varicella-zoster virus (VZV) infection]. AB - Sixty cases with varicella-associated neurological disorders from Japanese literature during recent 11 years were analyzed and compared with previous reports. Chief diseases were encephalitis (encephalopathy) (23.3%), cerebellar ataxia (21.7%), meningitis (18.3%), cerebral infarction (13.3%) and facial palsy (8.3%). Cerebellar ataxia, meningitis and cerebral infarction were found in young children under 9 years, and other disorders were seen also in older children and adults. Some cases had neurological symptoms before the appearance of skin rash. The number of cells in cerebrospinal fluid was increased in meningitis, encephalitis and myelitis. Though neurological complications due to varicella were rare, prognosis was not necessarily good, including several cases with death or severe sequelae. In our 4 cases of herpes zoster meningitis, marked intrathecal VZV-specific antibody production was found and they showed high antibody index. Oligoclonal band was found in one case. The pathogenesis of neurological complications of VZV infection was considered to be caused by direct viral invasion in herpes zoster and at least in some cases of varicella. Therapy with antiviral agents is necessary and vaccination is recommended for prevention. PMID- 8461163 TI - [Enterovirus infections]. AB - Non-polio enteroviruses are currently the most common agents of the central nervous system viral infection, and are the major causes especially in patients with aseptic meningitis. The practical problems with enterovirus meningitis revealed from the investigation of our patients are as follows. (1) The triad of symptoms of meningitis (fever, headache, vomiting) were seen only in 50% of the older children affected. The only manifestation of neonates with aseptic meningitis was fever. (2) In more than half of the patients, the cerebrospinal fluid showed polymorphonuclear predominance within 3 days from the onset. (3) The causal viruses were isolated frequently (70%) from the cerebrospinal fluid of the children with aseptic meningitis. (4) The patients more than 1 year of age had no sequela clinically. Among neonates and early infants, transient abnormalities of brain CT findings were seen in 40% and delayed speech in 30%. Their prognosis should be investigated more precisely. PMID- 8461164 TI - [AIDS virus]. AB - A Japanese child case of subacute progressive encephalopathy was presented. Not only the pathological findings of HIV growth in microglias, astrocytes and macrophages in the central nervous system, but also the pathobiological findings of neuronal apoptosis were shown as etiologies of HIV encephalopathy. Epidemiology, diagnosis, prophylaxis, fetomaternal transmission and embryopathy were discussed briefly. PMID- 8461165 TI - [Brain imaging in a case of early-onset acute disseminated encephalomyelitis]. AB - A case of early-onset acute disseminated encephalomyelitis was presented with her brain imaging. Two weeks after a nonspecific upper respiratory infection, a 14 month-old girl developed spastic paraplegia, difficulty in using left upper extremity and mental deterioration with aphasia. Steroid improved her clinical symptoms. However, 9 weeks later, when steroid was almost withdrawn, relapse with meningeal signs appeared. Reinstitution of steroid was started and 8 weeks later when meningeal signs disappeared, rehabilitation by physical therapist was started. Eighteen months later she recovered into normal intelligence and slight gait difficulty walking with left lower extremity weakness. CT showed extensive symmetric low density lesions in bilateral cerebral white matters and they almost resolved 8 months later. MRI showed extensive symmetric high signal lesions in bilateral cerebral white matters which were demonstrable in the sagittal image. Abnormalities in MRI were much improved 4 months later when she began to speak several words again. PMID- 8461166 TI - [A case with severe neurological involvement due to vitamin B1 deficiency associated with megaduodenum]. AB - We reported a case of 4-year-old boy with multiple vitamin deficiencies, especially vitamin B1 deficiency. He had megaduodenum associated with membranous stenosis on upper jejunum. He showed recurrent vomiting at his infantile period, and recently intermittent neurological symptoms. When he was admitted to our hospital, he could not walk and showed masked face, absent deep tendon reflexes, horizontal and vertical nystagmus, proximally dominant muscle weakness and multiple vitamin deficiencies. Oral administration of small doses of vitamin B1 (20 mg/day) could make remarkable clinical improvements. At three weeks after the treatment he could walk and run. Before the admission he had febrile convulsions and showed transiently striatal low density on CT image. We concluded that his neurological symptoms were due to vitamin B1 deficiency associated with megaduodenum. When a patient with intestinal anomaly shows neurological symptoms, we should think of vitamin deficiency. PMID- 8461167 TI - [A case report of arthrogryposis multiplex congenita with abnormal distribution of fiber type]. PMID- 8461169 TI - [Usefulness of 123I-amphetamine SPECT in evaluation of cerebral circulation by the acetazolamide test in patients with moyamoya disease]. PMID- 8461168 TI - [Effect of ethyl loflazepate on age-dependent epileptic encephalopathy]. PMID- 8461170 TI - Determining the accuracy and relevance of mortality rates for extremely low birthweight infants. PMID- 8461171 TI - Priorities and practice in tropical paediatrics. AB - More than 14 million children under 5 years of age die annually in the Third World, mainly due to diarrhoea, pneumonia, malaria and immunizable diseases. The problems of poverty, malnutrition, poor sanitation, illiteracy and high fertility that traditionally are associated with underdevelopment are now being compounded by social disruption due to rapid changes in lifestyle, new diseases such as AIDS and Third World debt. A vital part of the solution is provision of basic medical and education services to all, with emphasis on female literacy and improving the status of women. Key elements in providing basic medical services are delegation and empowerment. Doctors must delegate the delivery of essential child health services to appropriately trained and adequately supported auxiliaries. Parents, especially mothers, need to be empowered with the knowledge and resources to recognize and manage, or assist in the management of, their children's health problems. PMID- 8461172 TI - Screening for cryptantigen exposure and polyagglutination in neonates with suspected necrotizing enterocolitis. PMID- 8461174 TI - Infant botulism: a review in South Australia (1980-89). AB - Between March 1980 and March 1989 there were six identified cases of infant botulism. The presenting symptoms were predominantly poor feeding, lethargy and constipation, and the presenting signs were predominantly hypotonia, weak gag reflex and respiratory difficulty. All required intensive care and prolonged hospital stays. Recovery was eventually complete in all cases. Infant botulism is an uncommon condition but early recognition with adequate intensive care usually results in complete recovery. PMID- 8461175 TI - Paediatric management practices in Down syndrome: a follow-up survey. AB - In a follow-up survey to a 1984 study, 339 paediatricians in Australia were invited to complete a brief questionnaire in 1990, in which they indicated their usual recommendations, practices and advice when managing children with Down syndrome. The response rate was 67%. The results indicated that the most frequent paediatrician-initiated referrals were for early intervention and for discussion with other parents; these options were selected more frequently in 1990 than in 1984. While referral to a social worker was the next most frequent choice, it occurred less in 1990 than in 1984. Other increases in referrals were for physiotherapy and speech therapy. Paediatricians were more likely to support referral to a geneticist, speech therapist or cosmetic surgeon in response to a specific parental enquiry, and less likely to support referral to a social worker or to full-time care. There had been significant increases since 1984 in the likelihood that paediatricians would order audiology and investigation of thyroid and cardiac function. There was less opposition to the use of sedatives, and virtual cessation of the use of tryptophan. Paediatricians were more optimistic about the likelihood of persons with Down syndrome living independently, caring for their own finances, and marrying, but not about other developmental areas. PMID- 8461173 TI - Insulin dependent diabetes in pregnancy: impact of maternal blood glucose control on the offspring. AB - Definition of optimal glycaemic control in diabetic pregnancy may still be debated. Measures of glucose control (based on 4-6 daily glucose and frequent HbA1c values) were recorded in two series of diabetic pregnancies; one multicentre study (n = 92, 1979-82), and one study from our own institution (n = 113, 1983-85). The average pregnancy glucose levels were 5.9 mmol/L (third trimester only) and 6.5 mmol/L (all trimesters), respectively. Discriminant analysis (including pregnancy glucose, HbA1c, gestational age, diabetes duration and hypertension) revealed that gestational age only (first series) and gestational age and HbA1c independently of each other (second series) were significantly associated with the occurrence of severe neonatal morbidity present among 30 and 16.8% of the infants, respectively. The overall outcome was favourable. The findings of no perinatal mortality, normal premature delivery rate (8.9%) and a very low rate of severe maternal hypoglycaemia (4.4%) in series two support the feasibility of a strict but individualized management programme. PMID- 8461176 TI - What do health care professionals know about childhood asthma? AB - The aim of this study was to examine the level of knowledge about childhood asthma in paediatric nurses, pharmacists and general practitioners to assess their potential value as sources of accurate information for patients with asthma. The main outcome measure was the score obtained on an asthma knowledge questionnaire which had been validated previously. The maximum possible score was 31. Eighty-three general practitioners had a mean score of 28.1 (range 14-31); 82 pharmacists scored a mean of 24.2 (range 15-30) and 30 paediatric nurses had a mean score of 25.5 (range 16-30). General practitioners scored well in most questions but had some worrying deficiencies, particularly in distinguishing preventive therapy from symptom relieving medication. Pharmacists and paediatric nurses had a number of problems in certain important areas. In particular pharmacists as a group were unaware of many of the clinical features of asthma, had misconceptions, such as the need to avoid cow's milk, and recorded incorrect responses to clinical scenarios of acute treatment. Paediatric nurses tended to overestimate the side effects of inhaled medications, and also the value of auscultation. They had poor knowledge of exercise-induced asthma. The data overall suggest that specific educational strategies should be devised for different groups of health professionals who manage children with asthma and suggest that poor knowledge on the part of health care providers may contribute to morbidity. PMID- 8461177 TI - Usefulness of the Widal test in diagnosing childhood typhoid fever in endemic areas. AB - Data are presented for 2382 children investigated for fever in a Malaysian hospital between 1984 and 1987 when Widal tests and blood cultures were a routine part of every fever screen. There were 145 children who were culture positive (TYP-CP) for Salmonella typhi, while 166 were culture negative but were diagnosed as having typhoid (TYP-CN). Analyses of the sensitivity and specificity of combinations of initial Widal titres in predicting a positive S. typhi culture in a febrile child (culture positive vs the rest) showed the best model to be an O- and/or H-titre of > or = 1 in 40 (sensitivity 89%; specificity 89%). While the negative predictive value of the model was high (99.2%) the positive predictive value remained below 50% even for very high titres of O and H (> 1 in 640), at which point the specificity was 98.5%, supporting the clinical view that a high proportion of the TYP-CN patients really were typhoid but were missed by culture. The TYP-CN patients showed a very similar clinical and age profile to TYP-CP patients. The length of history of fever did not affect the initial Widal titre in culture positive cases. The Widal test in children remains a sensitive and specific 'fever screen' for typhoid although it will not identify all cases. In children, lower cut-off points for O- and H-titres should be used than are generally recommended. PMID- 8461178 TI - Evolution of asthma. PMID- 8461180 TI - Stillbirths, neonatal and post-neonatal mortality by race, birthweight and gestational age. AB - The birthweight and gestational age specific mortality of singleton Aboriginal and White infants born in Western Australia during the period 1980-86 is described. The analyses are based on the approximately 8000 Aboriginal and 143,000 White births notified through the Western Australia Midwives' system, which were linked to perinatal and infant death records. Overall, stillbirth, neonatal and post-neonatal mortality risks were significantly higher (P < 0.01) for Aboriginals than Whites. However, for specific birthweights and gestational ages, particularly for infants of lower birthweight and shorter gestations, Aboriginals had lower mortality risks than Whites. The ratio of Aboriginal to White mortality risks tended to increase with advancing age of death, suggesting that longer exposure to the well-documented poorer social and environmental conditions of Aboriginal infants increased the mortality risk. PMID- 8461181 TI - Essential fatty acid deficiency in parenterally fed preterm infants. AB - To determine the incidence of essential fatty acid (EFA) deficiency during short term fat-free parenteral nutrition, the authors investigated prospectively the EFA status of nine low birthweight (1145 +/- 343 g) preterm (28.2 +/- 1.9 weeks) infants, in whom delivery of dietary fat was delayed postnatally for 2-9 days. Serial determinations of plasma fatty acids showed that during fat-free alimentation, the major EFA, linoleic acid (LA), decreased rapidly (-0.75% total fatty acids per day), accompanied by a rise in endogenously produced non essential fatty acid, eicosatrienoic acid (Mead acid). Essential fatty acid deficiency was confirmed biochemically by an elevation in the triene-tetraene ratio in six of the infants, only one of whom developed clinical symptoms. Abnormal fatty acid profiles were corrected within a few days of fat delivery by either intravenous or enteral routes. Essential fatty acids and their metabolites are involved in a wide range of physiological functions vital to postnatal growth and development. Depletion of these nutrients can be corrected by providing a minimum of 0.25 g LA/kg per day (equivalent to 0.50 g/kg per day of 20% intralipid or 30-50 mL/kg per day of breast milk). PMID- 8461179 TI - Combined therapy with growth hormone and oxandrolone in adolescent girls with Turner syndrome. AB - Five adolescent girls with Turner syndrome (mean age 13.9 years, mean bone age 12.0 years) were treated with both recombinant human growth hormone (rhGH) and oxandrolone for 2 years with an average increment in height of 13.4 cm. The mean bone age advanced by only 1.2 years, providing an increase in the mean estimated mature height of 9.2 cm. We conclude that rhGH and oxandrolone benefit older teenagers with Turner syndrome because of an increased growth rate with slow progression of skeletal maturation. PMID- 8461182 TI - The cost of improving the outcome for infants of birthweight 500-999 g in Victoria. The Victorian Infant Collaborative Study Group. AB - The aim of this study was to conduct an economic evaluation of neonatal intensive care for extremely low birthweight (ELBW) infants born in the state of Victoria. Two distinct eras (1979-80 and 1985-87) were compared. Follow-up data at 2 years of age were available for all 89 survivors from the 351 live births in 1979-80, and for 211 of 212 survivors from the 560 live births in 1985-87. The overall cost-effectiveness for ELBW infants during 1985-87 compared with 1979-80 was $104,990 ($A 1987) per additional survivor, or $5390 ($A 1987) per additional life year gained. Cost-effectiveness improved with increasing birthweight. If the quality of life of the survivors was considered, the economic outlook was more favourable. The cost per quality-adjusted life year gained was $5090 ($A 1987), approximately one-tenth of that obtained from the only previous full economic evaluation of neonatal intensive care. Although neonatal intensive care is expensive, it compares favourably with some other health care programmes, particularly as the outcome for ELBW infants continues to improve. PMID- 8461183 TI - Insulin deficiency: effects on fetal growth and development. AB - Insulin deficiency in either the mother or foetus has significant effects on fetal growth and development. In the human, maternal insulin deficiency, or diabetes mellitus, leads to macrosomia and increased adiposity of the foetus, while specific fetal hypo-insulinaemia is associated with intra-uterine growth retardation. When maternal diabetes is induced in experimental animals, no consistent increases in fetal bodyweight are observed although the body fat content of the foetus is increased in the majority of species studied. The magnitude of the fetal weight gain during maternal diabetes appears to be determined by the body fat content of the foetus, the severity and duration of the diabetes and by the temporal pattern of maternal hyperglycaemia observed during pregnancy. The latter factors, in particular, influence the level of insulin in the foetus which, in turn, regulates the rate of intra-uterine growth. By contrast, fetal insulin deficiency has a more uniform effect on fetal growth and leads to impaired growth in both experimental and naturally occurring hypo insulinaemic conditions. Fetal insulin deficiency reduces fetal growth by decreasing nutrient uptake and utilization of the fetal tissues and by altering the circulating concentrations of the insulin-like growth factors. Consequently, deficiencies in either fetal or maternal insulin secretion during pregnancy can alter fetal growth and have important consequences for perinatal survival and postnatal morbidity. PMID- 8461184 TI - A fatal case of necrotizing enterocolitis in a neonate with polyagglutination of red blood cells. AB - An infant of 30 weeks gestation developed necrotizing enterocolitis (NEC) 8 days after birth and died 2 days later after a fulminating course. During her illness she received two blood transfusions, both of which produced sub-optimal rises in her haemoglobin and were associated with evidence of haemolysis. Retrospective analysis demonstrated T antigen (Tk) polyagglutination of the infant's red blood cells and donor plasma. Although bacterial cultures were negative throughout the course of the illness in this case, T antigen exposure is associated with certain anaerobic infections and with severity of NEC. Infants with NEC should be regularly screened for T antigen exposure and if this test is positive, plasma (immunoglobulin) containing infusions should be avoided. PMID- 8461185 TI - Chronic diaphragmatic pacing in a quadriplegic boy. AB - Diaphragmatic pacing is a method of long-term artificial ventilation that is preferable to other forms of ventilation in suitable patients. Its use is described in a 14 year old quadriplegic boy who was previously hospital dependent and required continuous positive pressure ventilation. PMID- 8461187 TI - New Zealand Cot Death study and missing data. PMID- 8461186 TI - Flunitrazepam in terminal care. AB - Flunitrazepam is a benzodiazepine of long half-life with sedative, anxiolytic, muscle relaxant and anticonvulsant properties. It has proved effective in controlling terminal agitation, confusion, restlessness, dystonia and fitting in adults and can be given by subcutaneous infusion in combination with other drugs. Its use in children during their terminal illness is described. Good symptom control without excessive sedation was achieved over the 24 h prior to death. PMID- 8461188 TI - Day care in Victoria. PMID- 8461189 TI - Non-ketotic hyperglycinaemia. PMID- 8461191 TI - Fringe benefits. PMID- 8461190 TI - Severe choanal stenosis complicating nasopharyngeal CPAP. PMID- 8461192 TI - The definition of oral health. PMID- 8461193 TI - The need for involvement--an interview with David Lloyd. Interview by Sharon Beesley. PMID- 8461194 TI - 'Emergency dental services'. PMID- 8461195 TI - 'The future of vocational training'. PMID- 8461196 TI - 'Temporomandibular joint and orofacial pain: clinical and medicolegal management problems'. PMID- 8461197 TI - 'A survey of patients seen in consultant clinics in conservative dentistry at Edinburgh Dental Hospital in 1990'. PMID- 8461198 TI - 'Profession in turmoil'. PMID- 8461199 TI - BDJ re-design. PMID- 8461200 TI - Duplication of maxillary molars. PMID- 8461201 TI - Latex allergies. PMID- 8461202 TI - pH changes in plaque after eating snacks and meals, and their modification by chewing sugared- or sugar-free gum. AB - Previous studies have suggested that if either sugar-free or sucrose-containing chewing gum is chewed after acidogenic meals or snacks, the plaque pH response to the latter is reduced and the potential for remineralisation of experimental white spot caries lesions is enhanced. This study has compared the effects of both gums on plaque pH (measured by the sampling technique) in 10 subjects who chewed the gums after standard acidogenic challenges (sucrose rinse, cupcake, and fried chicken dinner). The results showed that while both gums can significantly reduce the acid response, sugar-free gum appears more effective. PMID- 8461203 TI - The use of a caries detector dye during cavity preparation: a microbiological assessment. AB - During cavity preparation conventional tactile and optical criteria are used to assess the caries status of the enamel-dentine junction, cavity preparation being considered complete when this area is hard to a sharp probe and stain free. In the present study 201 cavities were prepared under rubber dam. When caries removal was considered complete using the conventional tactile and optical criteria, a caries detector dye (1% acid red in propylene glycol), which is claimed to stain 'infected' tissue red, was applied. Fifty-two per cent of cavities showed caries dye stain in some part of the enamel-dentine junction. Subsequent microbiological sampling of dye-stained and dye-unstained sites resulted in the recovery of low numbers of bacteria and revealed no difference in the level of infection of the two sites. It is concluded that the conventional tactile and optical criteria are satisfactory assessments of the caries status of tissue during cavity preparation and that subsequent use of a caries detector dye on hard and stain-free dentine will result in unnecessary tissue removal. PMID- 8461205 TI - Mercy mission to Guatemala. AB - The author joined an American team on one of their regular 'Mercy Missions' to Third World countries to treat underprivileged children. The patients' gratitude, the absence of complaining, operating conditions and quality of life were in stark contrast to that often seen in the UK. It was a heart warming experience for all members of the team. PMID- 8461204 TI - Controversies in cross-infection control. AB - The following article is intended to question certain procedures designed to prevent cross-infection. It is the first of a series of occasional articles describing new techniques, research, and new products, which it is hoped, may enable dental practitioners to update their knowledge of this rapidly changing subject. PMID- 8461206 TI - Temporary dressings. PMID- 8461207 TI - A different kind of cancer pain: the issue of family pain. PMID- 8461208 TI - Midazolam in terminal care. PMID- 8461209 TI - Controlling cancer and its symptoms. PMID- 8461210 TI - What is a non-profit hospice? PMID- 8461211 TI - Regulations vs. ideals: a case history of a hospice closure. PMID- 8461212 TI - Whole person care: beyond psychosocial and physical needs. PMID- 8461214 TI - A consensus statement by radiation oncologists regarding radiotherapy for bone metastases. PMID- 8461213 TI - A consensus statement by radiation oncologists regarding radiotherapy for bone metastases. PMID- 8461215 TI - Fetal origins of coronary heart disease. PMID- 8461216 TI - Mechanisms of ethanol-induced cardiac damage. PMID- 8461217 TI - Non-invasive three-dimensional localisation of arrhythmogenic foci in Wolff Parkinson-White syndrome and in ventricular tachycardia by radionuclide ventriculography: phase analysis of double-angulated integrated single photon emission computed tomography (SPECT). AB - A new tomographic technique combined with phase analysis was used to detect premature and ectopic ventricular contraction patterns in 15 patients with Wolff Parkinson-White syndrome and during ventricular tachycardia in seven patients. Data generated by gated single-photon emission computed tomography (SPECT) were analysed by backprojection of the Fourier coefficients, double-angulation, and integration to thick slices containing the ventricles, thus allowing visualisation of the contraction patterns in three perpendicular views. The results were compared with those of catheter mapping. In nine patients with Wolff Parkinson-White syndrome the site of initial contraction detected was identical with the site of the accessory pathway found by catheter mapping. The sites of origin of the ventricular tachycardias determined by catheter mapping were within 3 cm of the sites detected by the new technique. This new technique seems to be a promising non-invasive method for localising ectopic ventricular activity that will considerably shorten the time required for subsequent invasive procedures. PMID- 8461218 TI - Significance of reciprocal ST depression in acute myocardial infarction: a study of 258 patients treated by thrombolysis. AB - OBJECTIVE: To investigate the clinical significance of reciprocal ST depression on the presenting electrocardiogram in patients with acute myocardial infarction treated by thrombolysis. DESIGN: A prospective cohort analytical study. SETTING: A London district general hospital. SUBJECTS: Two hundred and fifty eight consecutive patients with acute myocardial infarction treated with thrombolysis. INTERVENTIONS: All patients underwent treadmill stress testing after a mean (SEM) of 10 (3) days; 200 patients (78%) were referred for coronary arteriography at 30 (16) days. MAIN OUTCOME MEASURES: Relation between reciprocal ST depression at presentation and several endpoints: time from start of chest pain to hospital presentation, electrocardiographic changes during early treadmill stress testing, presence of multivessel coronary disease, and clinical outcome in terms of recurrent ischaemic events (death, reinfarction, and unstable angina) during a 10 (range six to 12) month follow up. RESULTS: Presentation was generally early, but in this group of patients reciprocal ST depression was significantly related to the time from the start of symptoms, those with reciprocal change presenting on average one hour earlier than those without. Although reciprocal change on the presenting electrocardiogram was weakly associated with ST depression on treadmill stress testing, it was not indicative of remote ischaemia as a result of multivessel coronary disease or high grade collateralisation of the infarct related artery. There was no association between reciprocal change and the incidence of recurrent ischaemic events. CONCLUSION: Reciprocal ST depression on the presenting electrocardiogram seems to be a benign electrical phenomenon related to the time from the start of symptoms. It does not necessarily predict an adverse prognosis in patients treated by thrombolysis. PMID- 8461219 TI - Early treatment with captopril after acute myocardial infarction. AB - OBJECTIVES: To determine the effects of early treatment with captopril on haemodynamic function, neuroendocrine biochemistry, left ventricular structure, clinical outcome, and exercise capacity over one year from acute myocardial infarction. DESIGN: Randomised, double blind, placebo controlled comparison of captopril and placebo. SETTING: Coronary care units and cardiology departments of two university teaching hospitals in Glasgow. PATIENTS: 99 haemodynamically stable patients with acute myocardial infarction, selected on clinical grounds as being at risk of late ventricular dilatation. INTERVENTION: Captopril or identical placebo started between six and 24 hours after start of symptoms and continued for 12 months. Target maintenance dose was 25 mg three times a day. MAIN OUTCOME MEASURES: (a) Acute haemodynamic effects of treatment; (b) neuroendocrine biochemistry from admission to two months; and (c) change in echocardiographic measures of left ventricular size, clinical outcome, and exercise capacity after 12 months of treatment with a separate analysis of the effects of one month of treatment withdrawal on left ventricular volumes. RESULTS: Captopril caused acute reductions in mean (SEM) pulmonary artery pressure (2.48 (0.69) mm Hg) and systemic vascular resistance (260 (103)) dyn.s.cm-5). Over the first 10 hours captopril reduced mean arterial pressure by 12.1 (2.4) mm Hg compared with 3.8 (1.9) mm Hg in the placebo group. No patient had to be withdrawn from the captopril group because of hypotension. From day 1 onwards systolic and diastolic arterial pressures in the captopril treated group were slightly but not significantly lower than on placebo. There was no difference in the incidence of ventricular or supraventricular arrhythmia with treatment. Captopril prevented the day 3 peak in angiotensin II that occurred in the placebo group (peak concentration (interquartile range): 10.1 (4.8-19.4) pg/ml v 16.8 (4.3-46.3) pg/ml)) but had no effect on atrial natriuretic factor, arginine vasopressin, or catecholamines. Plasma atrial natriuretic factor remained above normal in both groups at two months after infarction. After one year left ventricular volume indices had increased less on captopril than on placebo: left ventricular end systolic volume index 5.4 ml/m2 v 14.7 ml/m2 (95% confidence interval (95% CI) of difference -14.6 to -3.9; p = 0.0011); left ventricular end diastolic volume index 8.4 ml/m2 v 19.0 ml/m2 (95% CI of difference, -17.0 to -4.2; p = 0.0016). Withdrawal of captopril for one month did not affect ventricular volumes. There was no difference in exercise capacity. CONCLUSIONS: Captopril started between six and 24 hours after acute myocardial infarction is not associated with significant hypotension. It suppresses activation of the renin angiotensin system but has no effect on plasma concentrations of other neurohormones. Atrial natriuretic factor remains raised at two months after myocardial infarction. Captopril significantly decreases left ventricular dilatation. This effect is not lost after one month of treatment withdrawal and is thus due to an alteration of left ventricular structure and not to a short lived haemodynamic action of captopril. Long-term treatment with captopril does not result in improved aerobic exercise capacity after acute myocardial infarction. PMID- 8461220 TI - Plasminogen activator inhibitor: a risk factor for myocardial infarction in diabetic patients. AB - OBJECTIVE: To determine whether diabetic patients admitted with acute myocardial infarction have impaired fibrinolytic activity due to raised plasminogen activator inhibitor compared with non-diabetic patients. SETTING: A district general hospital. PATIENTS: 90 non-diabetic and 38 diabetic patients admitted with acute myocardial infarction. RESULTS: Both plasminogen activator inhibitor activity and antigen were significantly higher in diabetic than in non-diabetic patients (24.7 (6.8) v 18.5 (6.8) AU/ml; p = 0.0001 and 64.2 (range 13.1 to 328.8) v 38.5 (range 10.9 to 173.7 ng/ml; z = 3.3; p = 0.0008) with a positive correlation between activity and antigen (rs = 0.51; p = 0.0001). In both groups, activity and antigen concentrations were significantly higher than in diabetic and non-diabetic subjects without coronary artery disease (p = 0.002 to 0.0001 for each comparison). Plasminogen activator inhibitor activity correlated significantly with admission plasma glucose (r = 0.32; p = 0.0001), glycated haemoglobin (r = 0.32; p = 0.0001), admission plasma insulin (rs = 0.48; p = 0.001), and Killip grade of heart failure both on admission (rs = 0.27; p = 0.001) and on discharge (rs = 0.22; p = 0.006), but not with cumulative creatine kinase MB isoenzyme release (rs = -0.08). There were similar but weaker correlations between tissue plasminogen activator antigen and admission plasma glucose, glycated haemoglobin, and insulin. In 18 patients (12 non-diabetic and six diabetic) plasminogen activator inhibitor activity was measured between six and 12 months (8.3 (1.6)) after the acute infarct and remained similar to activity on admission (24.8 (1.9) AU/ml (NS) for diabetic and 17.9 (6.9) AU/ml (NS) for non-diabetic patients) and was still significantly higher in diabetic than in non-diabetic patients (p = 0.007). CONCLUSION: These results show that diabetic patients have higher plasminogen activator inhibitor activity than non diabetic patients both on admission with acute myocardial infarction and at follow up six to 12 months later. Raised plasminogen activator inhibitor activity may predispose diabetic patients to myocardial infarction and may also impair pharmacological and spontaneous reperfusion after acute myocardial infarction thus contributing to the poor outcome in these subjects. PMID- 8461229 TI - Unruptured aneurysm of the sinus of Valsalva: a potential source of cerebrovascular embolism. AB - An unruptured aneurysm of the right sinus of Valsalva with intraluminal thrombus that displaced the right coronary artery ostium was diagnosed in a 30 year old Omani man who was investigated for uncontrolled grand mal epilepsy and residual left hemiparesis caused by occlusion of the right middle cerebral artery. Surgical intra-aortic closure of the aneurysm, which necessitated a saphenous vein graft to the right coronary artery, was successful. An aneurysm of the sinus of Valsalva is an unusual cause of a thromboembolic cerebrovascular accident. PMID- 8461223 TI - A loss of taurine and other amino acids from ventricles of patients undergoing bypass surgery. AB - OBJECTIVE: To study the changes in amino acid content of left ventricles of patients during cardiac surgery that involves cardiopulmonary bypass and cold cardioplegia. DESIGN: Biopsy specimens (up to 10 mg wet weight) from the left ventricle of 30 patients undergoing coronary artery bypass graft and valve replacement surgery on cardiopulmonary bypass (protected by cold cardioplegia with St Thomas' solution) were taken immediately before the infusion of the cardioplegic solution and just before the removal of the cross clamp, and were analysed for their amino acid content. RESULTS: Of the most abundant cellular amino acids in the left ventricle taurine, glutamine, glutamate, and aspartate, but not alanine, showed a significant fall during the period of cross clamping. A rise in intracellular sodium (Na) is known to occur during cold cardioplegic arrest so that an activation of an amino acid/Na efflux, similar to that seen in animal experiments, seems a likely mechanism. The anomalous behaviour of alanine suggests some recovery of metabolism. CONCLUSIONS: The loss of alpha amino acids (by contrast with the loss of taurine) will depress protein synthesis and reduce energy reserves after cardiac surgery. Attempts to preserve the concentrations of intracellular alpha amino acids must be balanced against the need to regulate intracellular Na concentration and hence intracellular pH and calcium ions. The presence of alpha amino acids in the cardioplegic solution (or in a resuscitation solution) should maintain the intracellular concentrations and favour activation of the taurine/Na symport to oppose the rise in intracellular Na concentration. Because the reservoir of tissue taurine is limited, the potential benefits of increasing the concentration of taurine in the heart by diet before surgery and addition of alpha amino acids to the cardioplegic solution merits further assessment. PMID- 8461222 TI - Progression of aortic valve dysfunction in 51 adult patients with congenital bicuspid aortic valve: assessment and follow up by Doppler echocardiography. AB - OBJECTIVE: To assess the pattern and progression of aortic valve dysfunction by serial Doppler echocardiographic examinations in ambulatory adult patients with congenital bicuspid aortic valve. DESIGN AND SETTING: Retrospective analysis of patients referred for Doppler echocardiography over a four year period. SUBJECTS: Fifty one adult patients with echocardiographic diagnosis of congenital bicuspid aortic valve had serial Doppler echocardiographic studies at least six months apart. There were 40 men and 11 women with a mean age of 36 years. MAIN OUTCOME MEASURE: Doppler echocardiographic values of aortic valve dysfunction. Cardiac events including endocarditis and aortic valve replacement were also evaluated. RESULT: Coarctation was present in five patients. 31 (61%) patients had a functionally normal bicuspid aortic valve defined as a mean gradient < 25 mm Hg and mild regurgitation. Significant aortic regurgitation was present in 15 patients (moderate in 12 and severe in three). Three patients had isolated aortic stenosis and two patients had combined aortic valve dysfunction. At a median follow up of 21 months (range six to 46 months), six patients had aortic valve surgery (one for aortic stenosis, three for aortic regurgitation, and two for endocarditis). Only 22 patients (43%) continued to have a functionally normal aortic valve. CONCLUSION: In this cohort of fairly young patients, aortic regurgitation is more common than aortic stenosis. Progression of aortic valve dysfunction occurs in patients with pre-existing valve dysfunction and even in those with normal aortic valve function at the initial echocardiographic examination. PMID- 8461224 TI - Ultrastructural quantification of collagen in human chordae tendineae. AB - OBJECTIVE: To determine collagen fibril diameter distributions in the chordae tendineae and to see whether there are any differences between right and left sides of the human heart. DESIGN: Collagen fibril diameters and the percentage volume occupied by collagen fibrils (as opposed to ground substance) were determined by means of a planimeter with a digitising tablet from electron micrographs printed at a magnification of 136; 000. MATERIAL: Human chordae tendineae were obtained at postmortem examination from seven subjects aged 50-75 years. MEASUREMENTS AND MAIN RESULTS: Histograms of collagen fibril diameter distributions showed a sharp, unimodal distribution. The mean collagen fibril diameters associated with the tricuspid and mitral valves were 41.1 nm and 40.5 nm respectively. The percentage volume occupied by collagen was about 39% for each valve. There were no significant differences for any of these values between the right and left sides of the heart. CONCLUSIONS: The greater pressures present on the left side of the heart are not reflected in any difference in collagen fibril diameters within the chordae tendineae compared with the right side. PMID- 8461226 TI - Initial experience with excimer laser angioplasty for coronary ostial stenoses. AB - The excimer laser has several potential advantages over conventional balloon angioplasty in the management of stenoses of the native coronary arteries and of the ostia of saphenous vein grafts. Its use in nine patients, eight of whom were classed as high risk, is described. Four lesions involved the ostia of saphenous vein grafts, three of protected left main stems, and two of native right coronary arteries. Stand alone laser was used in seven cases and laser with additional balloon angioplasty was used in two vein graft stenoses. Acute laser success was achieved in all cases, with a mean reduction of stenosis from 82% to 34% after laser alone and to 28% when balloon angioplasty was used as well. One patient died during laser angioplasty to a non-ostial lesion (procedural success rate 89%) and a second died ten weeks after the procedure. In one patient recurrent angina developed (clinical recurrence rate 25%) and restenosis was confirmed on angiography. Follow up angiography was also performed on the other six surviving patients, all of whom were symptom free and none of whom showed evidence of significant restenosis (restenosis rate 14%). With a mean follow up of 19.7 months the overall success rate was 67%. PMID- 8461221 TI - Circulating endothelin in children with congenital heart disease. AB - OBJECTIVE: To evaluate whether circulating endothelin, a peptide that is thought to play a part in mediating vascular tone, might be high in pulmonary hypertensive congenital heart disease. DESIGN: A prospective study with a radioimmunoassay technique to estimate urinary and plasma endothelin concentrations. SETTING: A supraregional referral centre for patients with congenital heart disease. PATIENTS: The 12 hour urinary endothelin concentration in young children with an increased pulmonary blood flow (n = 24, median age eight months) were compared with those in children with right ventricular outflow tract obstruction (n = 14, median age 1.5 years) and with those in healthy controls (n = 16, median age 1.8 years). The concentrations were also measured in adolescents with irreversible pulmonary vascular disease (n = 17, median age 18 years) and compared with those in controls of similar age (n = 19, median age 18.5 years). Also the plasma concentrations in the left atrium and pulmonary artery were measured in young children with either high (n = 11, median age 10.8 months) or low (n = 5, median age 1.0 year) pulmonary blood flow, in the peripheral arterial and venous blood of young children with either high (n = 13, median age 10.8 months) or low (n = 6 median age 1.9 years) pulmonary blood flow, and in the peripheral venous blood of seven healthy young children (median age 1.7 years). RESULTS: The urinary excretion of endothelin was similar in young children of a similar age, whether they had high, low, or normal pulmonary blood flow. Also, urinary endothelin excretion in older patients with irreversible pulmonary vascular disease was similar to that in normal subjects of similar age. Urinary endothelin excretion in normal young children, however, was significantly greater than that in normal older subjects (p = 0.0001). There was no transpulmonary or arteriovenous difference detected in either children with high or low pulmonary blood flow, and plasma concentrations sampled from the left atrium, pulmonary artery, and systemic artery and vein were similar in both groups. CONCLUSION: There was no evidence to implicate circulating endothelin in the pathogenesis of pulmonary vascular disease. PMID- 8461225 TI - Long-term follow up of patients treated with a software based antitachycardia pacemaker. AB - INTRODUCTION: Over the past decade, several advances have been made in the management of tachycardias by pacing techniques, but limited data are available on the long-term outcome of patients treated with antitachycardia pacemakers. PATIENTS AND METHODS: An antitachycardia pacemaker, the Intermedics Intertach, was implanted in 22 (17 female) patients with supraventricular tachycardia over a five year period. All were selected after detailed evaluation and testing of a temporary antitachycardia pacemaker system showed that their arrhythmia could be stopped promptly, reliably, and under different physiological conditions. RESULTS: The 22 patients have been followed up for a mean period of 57.3 (range 19-76) months. All except one of the patients has had frequent episodes of tachycardia reliably ended by the pacemaker. Complications have occurred in seven patients, necessitating removal of the pacing system in four. Of the 18 patients who continue to have pacemakers, seven are being treated with beta blockers or verapamil; no other antiarrhythmic drugs are being taken. CONCLUSIONS: Antitachycardia pacing is an acceptable long-term option for carefully selected patients with supraventricular tachycardia, but even after extensive testing a substantial number of the patients may continue to require drug treatment. Furthermore, the widespread use of curative techniques for supraventricular arrhythmias (catheter ablation and surgery) has decreased the need for this palliative treatment. PMID- 8461227 TI - Arterial duct angioplasty as an adjunct to dilatation of the valve for critical pulmonary stenosis. AB - OBJECTIVE: To assess the efficacy of arterial duct angioplasty in maintaining adequate ductal patency in neonates with critical pulmonary valve stenosis. PATIENTS: Two neonates presenting with cyanosis due to critical pulmonary valve stenosis with severe right ventricular hypoplasia underwent percutaneous balloon dilatation of the pulmonary valve. Despite successful dilatation, both remained cyanosed while receiving prostaglandin E2 infusions. RESULTS: Angioplasty of the arterial duct resulted in increased arterial oxygen saturations. Adequate arterial duct patency was maintained for three months during which time right ventricular dimensions increased enough to allow sufficient pulmonary circulation without the duct. CONCLUSIONS: Arterial duct angioplasty is an effective additional treatment for patients with critical pulmonary valve stenosis whose right ventricle is too small to provide adequate forward flow after balloon dilatation of the valve. Arterial duct angioplasty sustains adequate patency of the duct while the right ventricle grows sufficiently to undertake the pulmonary circulation. PMID- 8461228 TI - Acceleration of ventricular response to atrial flutter after intravenous adenosine. AB - Adenosine may be of therapeutic and diagnostic value in the emergency management of arrhythmias. It causes transient atrioventricular nodal block and thus ends paroxysmal supraventricular tachycardias that involve the atrioventricular node. Also, it may uncover underlying atrial arrhythmias by slowing the ventricular response. Its duration of action is brief and serious adverse effects have not been reported. A 12 year old patient with atrial flutter is presented, in whom intravenous adenosine was followed by acceleration of the heart rate to a potentially dangerous arrhythmia. PMID- 8461234 TI - Cardiac surgery: moving away from intensive care. PMID- 8461233 TI - Answers to complex questions cannot be derived from 'simple' trials. PMID- 8461231 TI - Correction of myocardial ischaemia after transcatheter embolisation of a small left coronary artery venous fistula. AB - A 50 year old woman presented with a history of angina and palpitation. She had a positive exercise test and thallium scintigraphy showed reversible ischaemia in the territory of the left anterior descending coronary artery. Coronary angiography showed a small coronary arteriovenous fistula arising from the bifurcation of the left main stem--that is, the origin of the left anterior descending and circumflex coronary arteries--with no evidence of coronary stenosis. The aberrant coronary artery was embolised with platinum microcoils delivered by a percutaneous, transcatheter, coaxial technique. The patient was subsequently symptom free with no evidence of ischaemia on exercise testing or thallium scintigraphy. This case suggests that when there is clear evidence of myocardial ischaemia even small coronary arteriovenous fistulas should be treated by embolisation. PMID- 8461230 TI - Pulmonary artery dissection in a patient with idiopathic dilatation of the pulmonary artery: a rare cause of sudden cardiac death. AB - A 31 year old man presented with a left hilar mass. Thoracic tomography showed this mass to be the pulmonary artery, and subsequently idiopathic dilatation of the pulmonary artery was diagnosed. He remained well until 11 years later when he died suddenly. Postmortem examination confirmed idiopathic dilatation of the pulmonary artery with death due to pulmonary artery dissection and cardiac tamponade. It seems likely that idiopathic dilatation of the pulmonary artery predisposed to fatal pulmonary artery dissection. PMID- 8461235 TI - The role of SPECT in the evaluation of skeletal trauma. AB - Single photon emission computed tomography (SPECT) has, in the last decade, established a critical role in routine diagnosis. Skeletal scintigraphy exemplifies the impact in improving detection of lesions by delineation of their site and size. The advantage of minimizing the superimposed radioactivity from overlying and underlying structures is typified by the readiness with which avascular necrosis of the femoral head can be identified by removal of the surrounding hyperaemia which masks the classical photopaenia. However, the ability to achieve an accurate image at a plane at a prescribed depth is most characteristically shown by the study of a vertebra, a bone of irregular contour and subject to a variety of pathological disorders at different sites within it. The various focal abnormalities resulting from these can be localized exactly, readily distinguishing, for example, those in the body from those in the natural arch. In particular, the alterations resulting from trauma, such as pars interarticularis stress fracture, are readily seen. Consequently SPECT has an indispensable role in the investigation and management of low back pain. However, the ability of SPECT to delineate abnormal accumulation has provided a new approach to the evaluation of knee pain, especially when acute such as that resulting from athletic injury, since the identification of the presence or absence of focal abnormalities can be critical to patient management. The frequency of these various disorders in which SPECT is so useful explains why the procedure has become such a routine high-volume examination is so many departments. PMID- 8461232 TI - Financial audit of antitachycardia pacing for the control of recurrent supraventricular tachycardia. AB - OBJECTIVE: To assess the financial implications of antitachycardia pacing in patients with frequent supraventricular tachycardia. PATIENTS: Intertach pacemakers were implanted in 25 patients (mean age 47 years, five men): 22 had atrioventricular nodal reentry tachycardia. The patients had failed a mean of 4.9 (range zero to eight) drugs and had been admitted to hospital 3.7 (zero to 31) times over a symptomatic period of 13.9 years (two months to 54 years). RESULTS: The mean admission time for implantation was 2.8 (two to seven) days. One patient with Wolff-Parkinson-White syndrome subsequently underwent surgery. Infection occurred in two patients, and pain over the pacemaker required its resiting in two. Two patients have had one admission each for tachycardia. Six patients remain on anti-arrhythmic drugs. Costs were calculated including value added tax, capital charges, and allocated overheads. The cost a year before pacing was 1174 pounds including drug costs, clinic visits, and hospital admissions. The mean cost of pacemaker implantation was 3364.22 pounds, including the pacemaker and lead, admission and procedure, readmissions and first pacing check. Subsequent annual follow up cost was 73.72 pounds including annual clinic visits and drug costs. The cost of pacing is 4241 pounds whereas medical management costs 7044 pounds assuming pacemaker life of six years: with a 10 year life the cost is 4537 pounds compared with 11,740 pounds: with a 12 year life the cost is 4685 pounds compared with 14,088 pounds. CONCLUSION: The excess cost of implantation of an antitachycardia pacemaker is minimal in patients with frequent supraventricular tachycardia despite drug treatment and is justified by excellent control of symptoms and reduction of drug use and hospital admissions. PMID- 8461236 TI - Factors causing prolonged hypoperfusion after transient ischemic attack. AB - Even during the symptom-free stages, patients with a TIA often experience cerebral blood flow disturbances. In order to evaluate the factors which cause this abnormality, we studied the cerebral blood flow disturbance, anatomy and clinical status in 21 patients after TIAs. The results of 99mTc-hexamethyl propylene-amine oxime SPECT were compared with CT, cerebral angiogram, cerebrovascular risk factors and clinical findings to determine which factor is most responsible for the hypoperfusion of brain after TIA. The overall sensitivity rates in detecting a lesion were 67% in SPECT and 19% in CT. The hypoperfused area tended to be large in patients who had intracranial, severe stenotic, multiple, or hemodynamically significant arterial lesions on the ipsilateral side. No such relationships were found between other examinations. We conclude that hypoperfusion after TIA essentially reflects a continuous cerebral blood flow disturbance that can be attributed to atherosclerosis of the cerebral arteries, with subsequent embolic and/or hemodynamic cerebral ischemia, although there may be a variety of processes. PMID- 8461238 TI - Cerebrocerebellar relationships in normal subjects and patients with dementia of the Alzheimer type: a SPECT study. AB - The relationships between blood flow in the cerebrum and the cerebellum was investigated in 21 normal subjects and 21 patients with dementia of the Alzheimer type (DAT). In normal subjects, only asymmetry in the frontal cortical blood flow was significantly correlated with asymmetry in the contralateral cerebellar blood flow. However, a significant correlation between asymmetry in the cerebral cortical blood flow in many areas and the blood flow in the contralateral cerebellum in DAT patients was observed. These results suggest the existence of a functional relationship between the cerebrum and the cerebellum in both normal and DAT groups, mediated by neuronal mechanisms through crossed fiber pathways. However, there are regional differences in the cerebrocerebellar relationship in normal resting and pathological states. PMID- 8461242 TI - Variant angina in thyrotoxicosis. AB - Thyrotoxicosis may exacerbate angina pectoris in patients with coronary artery disease but angina also occurs in thyrotoxic patients with normal coronary arteries. Four female severely thyrotoxic patients presented with apparent angina pectoris as a manifestation of their thyrotoxicosis. Two of them had transiently abnormal ECGs during pain. Treatment for thyrotoxicosis immediately stopped the chest pain, which did not recur. All patients had negative exercise ECGs, and one had a normal coronary angiogram. The possible mechanisms to explain this phenomenon are discussed. Coronary artery spasm has been demonstrated in thyrotoxic patients previously and may explain the features in these patients. An alternative hypothesis is that myocardial metabolism is fundamentally changed by thyrotoxicosis. We would recommend that thyroid function assessment should be considered in young female patients with atypical angina. PMID- 8461241 TI - Sydenham's chorea: a new look at an old disease. AB - Eight children with Sydenham's chorea were studied to illustrate the clinical characteristics and the outcome of the disease. Their ages ranged from 8 to 13 years and the male to female ratio was 1.7:1. Most of them had hemichorea, which frequently affected the right side of the body. The common presenting manifestations were involuntary movements, facial grimacing, clumsiness, and emotional instability. The duration of chorea ranged from one week to three years, with a median of 11 weeks. One half of the patients had associated mild carditis. Recurrences of chorea occurred only among patients who were not maintained on continuous penicillin prophylaxis. Haloperidol seemed to be an effective and tolerable agent in controlling the motor manifestations of the disease. PMID- 8461239 TI - Accumulation of thallium-201 in medullary thyroid cancer with negative serum calcitonin and carcinoembryonic antigens: a case report. AB - Thallium-201 (201Tl) scintigraphy has been used in the evaluation of thyroid neoplasm. Even though several authors have shown the usefulness of 201Tl scintigraphy in evaluating recurrent tumor of medullary thyroid cancer, the number of reports on primary thyroid cancer is limited. We presented a case of medullary thyroid cancer which showed 201Tl uptake in both early and delayed scans. This case had normal serum levels of calcitonin and carcinoembryonic antigen. PMID- 8461240 TI - A novel sustained-release formulation of ibuprofen provides effective once-daily therapy in the treatment of rheumatoid arthritis and osteoarthritis. AB - The efficacy and safety of a novel sustained-release formulation of ibuprofen given once-daily was compared with conventional-release ibuprofen tablets 400 mg given four times daily, in a single-blind, parallel-group study. This study was conducted at 84 general practice centres throughout the UK among patients with osteoarthritis or rheumatoid arthritis. An unequal randomisation in the ratio of 4:1 was carried out, with 463 patients who received sustained-release and 115 who received conventional-release ibuprofen providing evaluable data. In this study sustained-release ibuprofen was shown to be a more effective alternative to conventional ibuprofen therapy for the treatment of arthritic diseases in general practice, offering the convenience of once-daily dosing and the associated potential benefit of improved patient compliance. PMID- 8461237 TI - Dopamine D2 receptor SPECT imaging: basic in vivo characteristics and clinical applications of 123I-IBZM in humans. AB - The purposes of this study are to evaluate the utility of kit formulation, the basic in vivo characteristics, and clinical usefulness of dopamine D2 receptor imaging with 123I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrodinyl)m ethyl]- benzamide (123I-IBZM). We studied 22 normal controls, 3 early symptomatic Huntington's disease patients, and 1 patient with visual hallucination on and off neuroleptics. 123I-IBZM could be conveniently prepared with a high degree of purity from a kit, but with relatively low radiochemical yield. We demonstrated 123I-IBZM receptor binding equilibrium by performing serial SPECT scanning in a normal volunteer. The basal ganglia/frontal cortex (BG/FC) ratios plateaued after the specific binding reached equilibrium approximately 60 minutes after injection. The BG/FC ratio declined significantly with age. The ratios for the Huntington's disease patients were significantly lower than those for normal controls. The images of the patient off neuroleptic therapy showed dramatically increased BG activity compared with those obtained while on therapy. The BG/FC ratio provides an estimate of Bmax/Kd and hence the receptor density. It appears important to perform SPECT early in the equilibrium phase and at a fixed time after injection to obtain significantly high signal to noise ratios. 123I-IBZM is an ideal tracer for SPECT including a rotating gamma camera type which can provide estimates of the receptor density objectively by calculating the BG/FC ratio, and is a promising agent for the investigation of dopamine D2 receptors in clinical conditions. PMID- 8461243 TI - The prevalence of Chlamydia trachomatis infection among gynaecological patients. AB - The prevalence of chlamydia trachomatis infection in the population screened, at All Saints Hospital in Chatham between 1988 and 1990, was 6.3%. The main risk factors for cervical chlamydia infections in gynaecological patients were found to be an age less than 25, low socioeconomic status, and exposure to other sexually transmitted diseases. More research is needed to elucidate the factors that contribute to the differences in sociodemographic characteristics of this disease. Meanwhile it is clear that public health intervention is crucial to its control. The disease is frequently asymptomatic and occurs often in a population that is not seen routinely in standard STD outreach efforts. Furthermore, the chlamydia prone population is only moderately successful at referring sexual partners. PMID- 8461244 TI - Assessment of patients' knowledge about their illness and treatment. AB - One hundred and twenty two patients over the age of 65 were questioned about their knowledge of their illness and treatment. They were unaware of a quarter of both their illnesses and medications. There was a considerable lack of knowledge about certain groups of diseases and medications, while patients were much better informed about others. The possible reasons for this discrepancy are briefly discussed and some practical suggestions are put forward. PMID- 8461245 TI - How sound are recommendations for lowering cholesterol for the primary prevention of coronary heart disease? PMID- 8461246 TI - ACE inhibition in the 1990s. AB - Angiotensin-converting enzyme (ACE) inhibitors are now widely prescribed for the treatment of hypertension and heart failure. Their increasing popularity is based on impressive results from studies of efficacy in clinical situations and the realisation that they may have advantages over conventional treatment. This review will highlight some of the recent advances in our knowledge of the role of ACE inhibitors and will develop a rational approach to prescribing. PMID- 8461248 TI - An uncommon benign breast tumour--hamartoma. AB - Two patients who presented with mobile breast lumps which were later diagnosed to be hamartomas are presented, along with a brief review of current literature. These benign lesions are likely to be increasingly diagnosed because of routine mammographic screening and hence clinical awareness is paramount to prevent these lesions from being overtreated. Hamartoma of the breast is a rare benign breast lesion which is unfamiliar to most clinicians. We herein report two examples of such a lesion and review the recent literature. The hamartoma presents as a soft well-defined lump, causing considerable asymmetry of the breasts. PMID- 8461247 TI - The acute porphyrias. AB - The porphyrias are a heterogeneous group of rare inborn errors of metabolism caused by inherited enzyme defects in the haem biosynthetic pathway, resulting in overproduction of porphyrins. The porphyrias can be distinguished biochemically but may be difficult to differentiate clinically. Considerable advances have been made in the understanding of the enzymology and molecular biology of the porphyrias. The acute attack of porphyria may be a life-threatening condition, and an understanding of its many precipitating factors, clinical features and management is of importance in a disease with a significant mortality. PMID- 8461250 TI - An unusual cause for respiratory difficulty after thyroidectomy. AB - Problems with breathing immediately after extubation following thyroidectomy are rare, but can usually be attributed to a surgical error such as damage to one or both recurrent laryngeal nerves. Tracheomalacia may also cause respiratory distress following extubation. We present an unusual cause of failure to resume spontaneous respiration after thyroidectomy. PMID- 8461254 TI - Sex hormones and dexamethasone modulate interleukin-5 gene expression in T lymphocytes. AB - The ability of the sex hormones progesterone, testosterone and estradiol-17 beta and the glucocorticoid dexamethasone to modulate expression of the interleukin-5 (IL-5) gene in T cell lines has been investigated. The T cell lines used show analogous regulation of IL-5 gene expression to that occurring in T-lymphocytes, in that IL-5 mRNA levels are undetectable unless the cells are induced with phorbol myristate acetate (PMA). Progesterone and testosterone were as effective as PMA in inducing IL-5 mRNA levels in the T cell hybrid NIMP-TH1 and induced IL 5, -3 and -2 mRNA accumulation in the T cell lymphoma EL-4. Estradiol-17 beta also induced IL-5 mRNA accumulation but less effectively than testosterone. Nuclear run-on experiments suggested that the effects of progesterone, testosterone and PMA on IL-5 gene expression were mediated at the level of transcription. The presence of the protein synthesis inhibitor cycloheximide completely prevented PMA-induced synthesis of IL-5 mRNA by both NIMP-TH1 and EL-4 cells, indicating that induction of IL-5 mRNA via PMA stimulation requires de novo synthesis of a presumptive trans-acting factor(s). PMA-, testosterone- and progesterone-induced expression of the IL-5 gene was completely blocked by the anti-inflammatory steroid dexamethasone. Stimulation of IL-5 expression by PMA was relatively resistant to the immuno- suppressive drug cyclosporin A although inhibition did occur at very high levels. Testosterone- and progesterone-induced IL-5 gene expression was not inhibited by cyclosporin A. The in vivo significance of these findings are not yet clear but the results show that sex hormones have the potential to regulate cytokine gene expression in cells possessing the appropriate steroid receptors. PMID- 8461252 TI - Food induced anaphylaxis--death can and must be avoided. PMID- 8461251 TI - Isolated subglottic lymphoma: an interesting cause of dysphonia. AB - Isolated laryngeal lymphomas are exceedingly rare tumours: they tend to be greyish submucosal swellings and to respond well to radiotherapy. A case of subglottic lymphoma is presented, along with a review of previously reported cases of subglottic lymphomas. PMID- 8461253 TI - Cholesterol levels and coronary risks. PMID- 8461249 TI - Paradoxical cerebral embolism originating from thrombus in tumour veins as presenting manifestation of retroperitoneal liposarcoma. AB - The coincidence of pulmonary and systemic emboli suggests paradoxical embolism. We present the case of a young man in whom a blood clot travelled from the veins in a retroperitoneal liposarcoma via a patent foramen ovalis to the systemic arterial circulation. Young patients with embolic disease but no obvious source of thrombus may have underlying neoplastic disease. Venous thrombosis is a frequent complication of neoplastic disease. Arterial embolism associated with neoplasm is, however, not widely recognised. PMID- 8461258 TI - Vitellogenin synthesis in cultured hepatocytes; an in vitro test for the estrogenic potency of chemicals. AB - We describe here an in vitro technique to assess the estrogenic activity of chemicals. This technique is based on rainbow trout hepatocytes incubated in a basic medium free of any additional growth factors or estrogenic chemicals and uses the production of vitellogenin (VTG) as a marker for the estrogenic potency of the compounds tested. The system allows at least some of the metabolic transformations which are undertaken by the liver cells in vivo and could therefore be used for xenobiotic compounds which exhibit estrogenic activities after liver metabolic transformation. A dose-response curve was always consistently obtained using estradiol-17 beta (E2), with a mid point at around 100 nM E2 and a maximum response at around 1000 nM. Established estrogens such as 17 a 1 ethynylestradiol (EE2) or diethylstilboestrol (DES) were also tested. EE2 appeared to be equipotent with E2 and DES slightly less potent. E2 conjugates were, perhaps surprisingly, also very potent. Estradiol-3-sulfate was equipotent with E2 and estradiol-17 beta-glucuronide approx. 10% as potent. Other steroids such as androgens and progesterone, though active in the bioassay, were 3 orders of magnitude less potent than E2. Of the various steroids tested, only cortisol, at concentrations up to 50 microM, was completely inactive. Six different phytoestrogens were tested in the assay. All were weakly estrogenic, possessing approximately one thousandth the potency of E2 (they were as potent as the androgens and progesterone). All six phytoestrogens, as well as the androgens and progesterone, were tested in the presence of tamoxifen. In all cases tamoxifen reduced the production of VTG significantly, demonstrating that the estrogenic action of all of these compounds was most likely mediated by the E2 receptor. The potencies determined here may not reflect the situation in vivo but can provide complementary results about the activity of chemicals which need an hepatic metabolization to be estrogenic. Hepatocyte cultures would profitably be developed in other species to sustain these results. PMID- 8461255 TI - Binding of RU486 and deacylcortivazol to the glucocorticoid receptor is insensitive to sulfhydryl-modifying agents. AB - The differential sensitivity of the rat liver glucocorticoid receptor (GR) to sulfhydryl group modifying agents when bound to various agonist and antagonist ligands was studied. [3H]Triamcinolone acetonide (TA) binding was completely abolished by previous treatment of the unbound receptor with various N alkylmaleimides. On the contrary, [3H]RU486 binding was only slightly affected by treatment with N-ethylmaleimide (NEM) and more significantly decreased with maleimides bearing bulky substituents. Ligand exchange experiments demonstrated that, unlike the agonist TA, the antiglucocorticoid RU486 was unable to protect the GR binding site from the effect of NEM. This lack of protection would seem to be due to the presence of the bulky 11 beta-substituent in RU486 since RU26988 and RU28362, two 11 beta hydroxylated glucocorticoids bearing the same 17 alpha propynyl side chain as RU486 but lacking the 11 beta-substituent could protect GR against NEM. The ability of a GR ligand to prevent NEM inactivation of TA binding appeared unrelated to its agonist or antagonist nature: deacylcortivazol, a potent agonist, afforded no protection whereas antagonists of the 17 beta carboxamide series did. These data strongly suggest that compounds bearing bulky substituents on the steroid A and/or C rings, like deacylcortivazol and RU486, are positioned differently from canonical glucocorticoids in the steroid binding groove of the GR. PMID- 8461256 TI - Altered patterns of proteins released in vitro from oviductal and uterine tissue from adult female mice treated neonatally with diethylstilbestrol. AB - Proteins released during incubation in vitro of oviductal and uterine tissues from 8-week-old female NMRI mice treated neonatally with diethylstilbestrol (DES) or vehicle were studied. The objective was to study if neonatal DES treatment altered the patterns of proteins released from the oviduct and uterus, as earlier studies had shown a detrimental effect of the oviductal environment in DES exposed females on early embryo development. In separate experiments nonlabeled and 35S-labeled proteins released from oviductal/uterine tissues during organ incubations were characterized with 1 and 2D gel electrophoresis. The incubation media of both oviducts and uteri from DES females had increased levels of a serum derived nonlabeled protein, identified as apolipoprotein A1. The amount of this protein in the incubation medium was not influenced by previous ovariectomy but increased by in vivo treatment with estradiol, in both ovariectomized controls and DES treated females. Three other unlabeled proteins were consistently found in higher amounts in the incubation media from DES exposed oviduct/uterine tissue, than in incubates of control tissue. In tissue incubates of oviducts from DES females, three synthesized proteins (35 kDa-pl 6.2, 112 and 143 kDa) were released in lower amounts and two in higher amounts (53 kDa-pl 6.6 and 53 kDa-pl 6.8) than in controls. In uterus from DES treated females one labeled protein was released in increased amounts (80 kDa-pl 6.7) and one in decreased amounts (43 kDa-pl 6.6), when compared with controls. In estrogen induced uterine luminal fluid from 8-week-old DES treated females the levels of four proteins (26, 42, 53 and 97 kDa) were increased and two (24 and 32 kDa) were decreased. These results show permanent alterations in levels of secreted proteins in both the oviduct and uterus of adult but neonatally DES treated females, which could be of importance for their poor reproductive performance. PMID- 8461257 TI - Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis. AB - A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect. PMID- 8461260 TI - Characterization of rat uterine estrogen receptors in vivo. AB - In vivo binding of [3H]estradiol ([3H]E2) in the rat uterus was performed by an intraluminal perfusion of the ligand for different time periods. In this way the binding takes place in the intact organ before processing the tissue. In 10 min, with 10 nM [3H]E2 apparent saturation or steady state incorporation of the [3H]E2 was achieved with a similar distribution of the label between cytosol and nuclear fractions. In vitro, the subcellular localization of the estrogen receptor (ER) is influenced by the extent of tissue damage. With the intact organ the ER subcellular distribution approaches that of the in vivo perfusion. With increasing [3H]E2 in the perfusate it was possible to obtain a "saturation" curve and to derive the kinetic parameters. For cytosol: Kd 16 nM; Bmax 235 fmol/mg prot. For nucleus: Kd 2.7 nM; Bmax 103 fmol/mg prot. To follow the time course of the ER movement in vivo, "pulse and wait" experiments were designed. Both uterine horns were perfused for 1 min. One of the horns was immediately processed (0 time) and the other was left in place after the perfusion for different periods. At 0 time 90% of the bound label appeared in the cytosol. At 5, 15 and 30 min, the label in the cytosol decreased and that of the nucleus increased approx. to 50%. Thus, translocation of the bound label from cytosol to nucleus was apparent. The role of the cytoplasm-nucleus ER traffic in the regulation of gene transcription by estrogens is discussed. PMID- 8461265 TI - The Kallmann's syndrome variant (KSV) model of the schizophrenias. AB - The KSV model of the schizophrenias proposes that up to 70% of schizophrenics have a pathogenic allele, or abnormal expression, of the KALIG-1 gene which is located at Xp22.3. This gene encodes a nerve-cell adhesion molecule (N-CAM) like protein, and is deleted in 66% of patients with Kallmann's syndrome, anosmia with secondary hypogonadism. Although superficially distinct, the schizophrenias and Kallmann's syndrome show numerous parallel trait defects which occur with a similar sex distribution. These defects are usually more profound in Kallmann's syndrome. Occasionally, Kallmann's patients exhibit additional defects, such as ichthyosis, which are due to the further deletion or translocation of adjacent genes. Since schizophrenics exhibit virtually all known trait defects in Kallmann's except these, it suggests that the aberrant genes are defective, but not deleted in schizophrenia. It also appears that compensatory mechanisms, involving serine proteases, are active in schizophrenia, which largely preserve fertility, but at the expense of an increased vulnerability to develop a psychosis by an episodic disruption of the blood-CSF barrier. Consequently, schizophrenia is rare in Kallmann's patients, while most schizophrenics are capable of reproduction. PMID- 8461259 TI - Sex hormone binding globulin and non-protein-bound oestradiol in postmenopausal patients with primary biliary cirrhosis and normal controls. AB - Several studies have suggested that patients with primary biliary cirrhosis (PBC) have an increased risk of a number of medical conditions related to their oestrogen levels. This study has measured sex hormone binding globulin (SHBG) binding capacity, total oestradiol levels and percentage non-protein-bound (NPB) oestradiol and calculated the concentration of NPB oestradiol, in postmenopausal subjects in the following groups; normal controls, early PBC, advanced PBC and advanced PBC who were receiving therapy. Mean SHBG levels were higher in all groups of patients with PBC than in controls. No significant difference was observed in total or biologically active oestradiol between the four groups. PMID- 8461261 TI - Generation of estradiol within the pregnant guinea pig uterine compartment with special reference to the myometrium. AB - Between about 50 and 58 days of gestation, the guinea pig chorion becomes attached in its entirety to the uterine wall, suggesting a facilitation of transfer of agents such as steroids between these tissues. At a time between 59 and 64 days, relaxation of the pubic symphysis starts, and anywhere from 5 to 8 days after that event delivery takes place. The present in vitro study was undertaken to evaluate estrone sulfate as a substrate for local production of estradiol, via the action of estrogen sulfatase and 17-hydroxysteroid dehydrogenase, in chorion, endometrium and myometrium taken at four distinct stages of gestation, as follows: 50 days, representing pre-chorion attachment to the uterus (stage 50); 1 or 2 days before pubic symphysis relaxation (minus 1 day, or -1 day); 1 day following relaxation (+1 day); and 1-2 days before delivery (late, or L). At these same stages, the metabolite patterns formed from estradiol were evaluated for endometrium and myometrium. Each of the tissues behaved somewhat differently. Overall hydrolysis of estrone sulfate by endometrium and myometrium exceeded that by chorion. Generation of free steroid from estrone sulfate increased 3-fold in chorion between stages 50 and -1 and during this period estradiol production from estrone sulfate increased 9-fold and continued to rise until delivery. Cytosolic estrogen sulfotransferase activity of chorion decreased 7-fold between stages 50 and -1. This suggested a tissue environment geared to producing potentially active estradiol. However, myometrium converted very little estrone into estradiol until just before delivery despite the facile formation of estrone from estradiol at stages -1, +1 and L. The control of estrogen metabolism by interaction of tissues in the uterus and by some form of enzyme regulation in these tissues suggests a possible role for locally produced estrogen in the stages leading up to parturition. PMID- 8461268 TI - Training novice raters on the Negative Symptom Assessment Scale. AB - The Negative Symptom Assessment (NSA), a scale for rating negative symptoms of schizophrenia, has been shown to have high interrater and test-retest reliabilities as well as high concurrent validity with similar instruments. In this study, the facility of clinicians unfamiliar with the NSA to learn this scale was evaluated. After attending a 30-min training lecture, 27 experienced researchers, who had never previously used the NSA, viewed and rated a videotaped, semi-structured NSA interview of a schizophrenic patient. These ratings were compared with those of an experienced rater. Scores for most items met our criteria for learning with this level of training. These data demonstrate that high levels of agreement with experienced raters can be achieved on the NSA after brief periods of training. PMID- 8461266 TI - Positive and negative symptoms in the psychoses. Re-analysis of published SAPS and SANS global ratings. AB - The validity of the simple dichotomy between positive and negative symptoms was examined by reanalysing the results of published studies using global ratings from Andreasen's SAPS and SANS. Global ratings from our own sample of 114 diagnostically heterogenous psychotic patients were also analysed. In none of the studies was a simple positive-negative dichotomy an adequate representation of symptom structure. The most commonly occurring structure consisted of three independent groups: Hallucinations/Delusions, Positive Thought Disorder and Negative Symptoms. These findings applied to both manic and schizophrenic groups of patients. An important implication of these results for future studies is that combining positive symptoms into a single scale is inappropriate because possibly differential relationships between Hallucinations/Delusions and Thought Disorder and a variety of external measures may be obscured by such a means of data reduction. PMID- 8461264 TI - Pathway and kinetics of prednisolone metabolism in the human placenta. AB - Prednisolone is metabolized in the perfused human placental lobule to prednisone, 20 alpha-dihydroprednisone, 20 beta-dihydroprednisone and 20 beta dihydroprednisolone. The pathway of metabolite formation was defined in perfusions of placental lobules using prednisone and 20 beta-dihydroprednisone separately as substrates and with prednisolone co-perfused with glycyrrhetinic acid, a potent inhibitor of the 11-oxidase component of the 11 beta hydroxysteroid dehydrogenase enzyme system. The pattern of metabolites identified from 6 h samples indicated a reversible formation of prednisone from prednisolone, the production of the 20 alpha- and 20 beta-dihydro metabolites of prednisone from prednisone, the formation of 20 beta-dihydroprednisolone from 20 beta-dihydroprednisone only and no direct formation of 20 beta dihydroprednisolone from prednisolone. Kinetic analysis at two substrate concentrations confirmed that the formation of three of the four steroid metabolites followed first order kinetics. In perfusions with an initial prednisolone concentration of 1 microgram/ml (n = 4) or 100 ng/ml (n = 3), the rate constants obtained were (mean +/- SD, maternal compartment, h-1): prednisone, 1.97 +/- 0.49 and 2.25 +/- 0.15, P > 0.1; 20 alpha-dihydroprednisone, 0.0006 +/- 0.0004 and 0.0017 +/- 0.0006, P < 0.1; 20 beta-dihydroprednisone, 0.15 +/- 0.022 and 0.15 +/- 0.0077, P > 0.1. In contrast, the rate constant for formation of 20 beta-dihydroprednisolone at an initial prednisolone concentration of 100 ng/ml (0.083 +/- 0.0095 h-1) was significantly (P < 0.01) greater than the corresponding rate constant at the higher initial prednisolone concentration (0.039 +/- 0.015 h-1). A significant increase (P < 0.05) was observed for the formation of 20 beta-dihydroprednisolone at the end of 6 h perfusions at the lower initial substrate concentration (11.2 +/- 1.9%) compared with the 1 microgram/ml concentration (6.0 +/- 2.5%). PMID- 8461262 TI - Changes in pituitary, hypothalamic and brain progestin-metabolizing enzyme activities during lactation. AB - Progesterone 5 alpha-reductase activity and 5 alpha-dihydroprogesterone 3 alpha hydroxysteroid oxidoreductase (3 alpha-HSOR) activities (NADH- and NADPH-linked) were measured in anterior pituitaries, hypothalami and brains from lactating rats (8 and 21 days postpartum) and non-lactating (60-day-old cycling) rats. Tissue levels of these three enzyme activities varied significantly among the three groups examined. In terms of pituitary, mean levels of both of its 3 alpha-HSOR activities were 40-140% higher in actively lactating rats (8 days postpartum) relative to mean levels in lactating rats at weaning (21 days postpartum) or in non-lactating rats. There were no differences in pituitary progesterone 5 alpha reductase activity among the three experimental groups. In the hypothalamus, the NADPH-linked 3 alpha-HSOR was elevated (50%) at 8 days of lactation compared to the group at 21 days. Hypothalamic NADH-linked 3 alpha-HSOR levels did not vary among the 3 groups. Hypothalamic progesterone 5 alpha-reductase levels in the actively lactating and weaning groups were 30% lower than those of the non lactating group. Brain levels of progesterone 5 alpha-reductase were also lower in these two lactating groups (35-55%) as compared to the non-lactating control group. In brain, NADPH 3 alpha-HSOR activity did not vary among the three groups, but levels of NADH 3 alpha-HSOR activity were lower (40-50%) in the weaning group as compared to the actively lactating and control groups. These findings suggest the possibility that tissue changes in these progesterone-metabolizing enzyme activities during lactation and at weaning are influencing the in situ supply of 3 alpha,5 alpha-tetrahydroprogesterone and 5 alpha-dihydroprogesterone and their derivative effects on GABAA receptor activity and prolactin and gonadotropin release. The decreased activity of progesterone 5 alpha-reductase in hypothalamus and brain would presumably reduce in situ 5 alpha-dihydroprogesterone formation while increases in 3 alpha-HSOR activity would suggest higher in situ 3 alpha,5 alpha-tetrahydroprogesterone formation, especially in the pituitary. PMID- 8461263 TI - Corticosteroid side chain oxidations--3. Evidence for isomerization and direct oxidation reactions in the formation of steroid 21-oic acids by rabbit liver cytosol. AB - Isomerase complexes that oxidize the alpha-ketol side chain of deoxycorticosterone (DOC) to pregnolic and pregnenoic acids without the addition of cofactors have been purified from rabbit and hamster liver cytosols. The isomerase complex in rabbit liver cytosol was partially resolved from a NAD dependent dehydrogenase that oxidized the glycol side chain of 20 beta-dihydro DOC to the 20 beta-hydroxy-21-oic acid. Corticosterone (B) and 20 beta-dihydro B were less active substrates than DOC or 20 beta-dihydro DOC with the corresponding preparations. The rabbit resembles other rodent and human species in that isomerization and oxidation at C21 is the major pathway of acid formation whereas direct oxidation at C21 may only be of significance with metabolites that have the glycol side chain. PMID- 8461270 TI - Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal. AB - Haloperidol and reduced haloperidol plasma concentrations were measured in twelve schizophrenic patients upon cessation of haloperidol decanoate (HLD) treatment. Each patient received HLD 100 mg every 4 weeks for five injections. After the fifth injection, HLD was discontinued. Haloperidol and reduced haloperidol plasma concentrations were obtained prior to cessation and at weeks 1, 3, 4, 5, 7, 9, 11, and 13 post-injection. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC. Both haloperidol and reduced haloperidol plasma concentrations were detectable 13 weeks post HLD discontinuation. Maximal haloperidol plasma concentrations were observed at one week post cessation and gradually declined. The mean elimination half-life for haloperidol was 27.4 +/- 8.6 days (range 19.0-47.0 days). Reduced haloperidol plasma concentrations declined very slowly. Our results show that both haloperidol and reduced haloperidol plasma concentrations can remain for extended time periods after HLD is discontinued. PMID- 8461267 TI - Cholinergic hyperactivity and negative symptoms: behavioral effects of physostigmine in normal controls. AB - Intravenous infusion of physostigmine (a centrally active anticholinesterase agent) in normal subjects leads to a syndrome of psychomotor inhibition; this has been proposed as a model for selected symptoms of depression. In view of its similarity to the negative schizophrenic syndrome, we compared the 'physostigmine syndrome' to the negative symptom profile by evaluating the behavioral effects of intravenous physostigmine infusion in seven normal volunteers. Observer ratings and self description revealed significant withdrawal, apathy, alogia, lethargy, decreased energy, slowed thoughts, diminished affective responsivity, and reduced hedonic capacity. Subjects did not report sadness, ideas of hopelessness, worthlessness, or guilt. These findings support the implication of cholinergic hyperactivity as one mechanism in the pathophysiology of negative schizophrenic symptoms. PMID- 8461269 TI - Differential effects of haloperidol on negative symptoms in drug-naive schizophrenic patients: effects on plasma homovanillic acid. AB - After 5 weeks of haloperidol, positive symptoms in drug-naive schizophrenic patients substantially subsided. Negative symptoms, although with a different temporal pattern, decreased after the fifth week of haloperidol treatment; specifically, a decrease was seen in anhedonia and affective flattening, whereas avolition-apathy and attentional impairment presented no changes. Alogia showed a decrease during the third week and a trend to return to placebo scores during weeks 4 and 5. Changes in affective flattening, alogia and attentional impairment correlated with changes in positive symptoms. During placebo, plasma homovanillic acid (HVA) correlated with negative symptoms and with changes presented by negative symptoms between the first and the fifth treatment week. These data show that negative symptoms respond differentially to neuroleptics and suggest that avolition-apathy may represent a different behavioral component of the schizophrenia process. PMID- 8461271 TI - Visual controlled information processing resources and formal thought disorder in schizophrenia and mania. AB - Visual selective attentional performance under low and high processing load conditions was examined in patients with schizophrenia (n = 20), or bipolar affective disorder-manic type (n = 21) and a group of normal control subjects (n = 18). Although schizophrenic patients demonstrated significantly more impaired cognitive performance than normal controls, bipolar patients were found to be as deviant as the schizophrenic patients on almost all of the performance variables. Positive thought disorder under high processing load demands was moderately correlated with schizophrenic patients' response processing ability. In contrast, negative thought disorder ratings were found to be moderately associated with reaction time performance during high processing demands for both patient groups. These findings are discussed with regard to the relationship between selective attention, visual-motor controlled information processing deficits, and thought disorder in psychosis. PMID- 8461273 TI - Concordance for gender in sib pairs affected with schizophrenia and related disorders. AB - An excess concordance by sex among siblings affected with schizophrenia has been proposed by some previous and recent investigators. However, this hypothesis has not been supported by some recent studies having complete ascertainment of probands and relatives. The present report is based on sibships with multiple affected members derived from a family study of systematically recruited inpatients (146 probands with schizophrenia and 132 probands with other psychotic disorders). Evidence for an excess concordance rate for gender among proband sibling pairs with both members affected is suggested under a broad definition of illness. PMID- 8461272 TI - A comparative study of obstetric history in schizophrenics, bipolar patients and normal subjects. AB - Information on pregnancy and birth complications was collected for 46 patients with DSM-IIIR schizophrenia or bipolar disorder and for 23 normal controls. Pregnancy complications were more frequent and birth complications more frequent and more severe in schizophrenics than in bipolar patients or in normal controls. In contrast with other findings in the literature, more obstetric complications (OCs) were found in female than male schizophrenic patients. PMID- 8461274 TI - Handedness in twins with schizophrenia: was Boklage correct? AB - Boklage's report of increased non-right handedness among monozygotic twins with schizophrenia has been cited as evidence to support an association of abnormal brain lateralization with the development of schizophrenia. The present study found no such association. Two previous attempts to replicate Boklage's findings (Luchins et al. 1980; Lewis et al. 1989) also reported little support. Studies of twin handedness do not appear to support an association of brain lateralization and schizophrenia. PMID- 8461276 TI - Premorbid functioning, cognitive functioning, symptoms and outcome in schizophrenia. AB - In this study we examined the relationship between premorbid functioning, outcome, cognitive functioning and positive and negative symptoms of schizophrenia. Cognitive functioning and symptoms were examined longitudinally in a sample of 39 subjects with schizophrenia (according to the DSM-III criteria). Subjects were assessed at admission to hospital and six months later during a period of relative remission. Premorbid functioning was significantly associated with negative symptoms but not with positive symptoms at both the acute phase and the remitted phase of the illness. Outcome was also associated with negative symptoms at admission and with both positive and negative symptoms at follow-up. Deficits on cognitive tests of verbal reasoning and concept formation were significantly associated with poor premorbid functioning and outcome. PMID- 8461275 TI - Cholesterol, heart disease and the brain: an opportunity in research and a disaster in public health education? PMID- 8461278 TI - Thalamic radiodensity and cognitive performance in mild and moderate dementia of the Alzheimer type. AB - Eighteen patients with mild to moderate dementia of the Alzheimer type underwent cranial computed tomography (CT) and tests of visual attention, recognition and learning. Two subgroups emerged. Subgroup 1 was made up of ten patients who showed impaired visual recognition learning and memory, but intact attention in marked contrast to subgroup 2, which was made up of eight patients, in whom all of these functions were impaired. Planimetric and densitometric CT measurements yielded one significant difference between the two subgroups: a decreased radiodensity in the dorsomedial thalamus of the patients from subgroup 2. Lower radiodensity in the right dorsomedial thalamic area was significantly correlated with impaired performance on the test of attentional set shifting, more specifically, with deficits at the reversal learning stage. These results are interpreted in the context of recent evidence linking reversal learning to a neural network comprising the cholinergic basal forebrain, the amygdala and the orbitofrontal cortex, as well as the mediodorsal nucleus, and recent evidence of cholinergic deficits in this structure in patients with Alzheimer's disease. PMID- 8461277 TI - Structure and promoter organization of the human monoamine oxidase A and B genes. AB - Monoamine oxidase (MAO) A and B play an important role in regulating levels of biogenic amines. MAO A and B cDNAs have been cloned and the deduced amino acids share 73% sequence identity. The genes for MAOA and B are comprised of 15 exons interspersed by 14 introns, span at least 60 kb and exhibit identical exon-intron organization. These findings suggest that the MAOA and MAOB genes are derived from the duplication of a common ancestral gene. The core promoter region of MAOA is comprised of two 90 bp repeats, each of which contains two Spl elements and lacks a TATA box. The MAOB core promoter region contains two sets of overlapping Spl sites which flank a CACCC element all upstream of a TATA box. The different organization of the MAOA and MAOB promoters may underlie their different cell and tissue specific expression. PMID- 8461279 TI - Emotional-aversive nature of the behavioral response induced by carbachol in cats. AB - Intrahypothalamic-preoptic application of carbachol induces a characteristic, emotional-aversive response in cats similar to their natural defensive behavior. This study was undertaken to provide quantitative evidence that the magnitude of the carbachol-induced, emotional-aversive response follows the same rules as natural responses to threat. An aversive emotional response can be described in terms of a spatiotemporal relationship between the animal and the relevant threat stimulus (potential danger). The physical distance to the threat stimulus and its movements should be predictive of the magnitude of the emotional response. The goal of the study was to test the relationship for the carbachol-induced response. The presentation of a threat stimulus (a human hand) to cats injected with carbachol caused a significant increase in vocalization. The magnitude of the response was inversely proportional to the physical distance between the cat and the threat stimulus. The hand in motion caused significantly longer vocalization than the immobile hand and cats not familiar with the experimental situation vocalized significantly more than those that had been exposed to the hand before. The spatiotemporal relationship between the animal and the threat stimulus strongly suggests that the carbachol-induced response is emotional and aversive in nature and does not differ from the relevant natural responses. PMID- 8461281 TI - Absence seizures associated with panic attacks initially misdiagnosed as temporal lobe epilepsy: the importance of prolonged EEG monitoring in diagnosis. AB - While temporal lobe epilepsy is often considered in the differential diagnosis of patients with anxiety or panic disorders, other types of epilepsy can confound the presentation or treatment of adults with panic disorders. The cases of two patients are presented who were initially thought to have temporal lobe epilepsy producing panic attacks, but who were subsequently found to have primary generalized seizures. The clinical implications are discussed. PMID- 8461282 TI - Tranylcypromine withdrawal phenomena. AB - The gradual or abrupt withdrawal of tranylcypromine can result in syndromes ranging in severity from mild discomfort to incapacitation. Five patients were subjected to the withdrawal of tranylcypromine. Vignettes describing the withdrawal syndrome experienced by these patients are presented. These patients suffered from severe depression or impairment of cognition in association with a reduction in their daily dose of tranylcypromine. The authors conclude that reductions in a patient's dose or the discontinuation of tranylcypromine warrant the careful supervision of a physician. PMID- 8461280 TI - Effects of adrenal cortex hormones on limbic structures: some experimental and clinical correlations related to depression. AB - Cushing's disorder and depression present overlapping although not identical psychological symptomatology. In turn, a subset of patients with affective disorders present with hypercortisolemia and disturbances, specifically disinhibition, of the hypothalamic hypophysio adrenal axis (HHAA). Memory disturbances, in particular, biasing toward negative contents, overlapping sleep abnormalities (marked reduction of stages 3 and 4) increased fatigue and loss of energy, attentional deficits and irritability, are just part of the common symptomatology presented by patients with both Cushing's disorder and depression. All of these behavioral manifestations are known to be affected by adrenal steroid hormones. There is consensus that hippocampal structures are a main target for adrenal steroid hormones; hence, these neural regions are some of the most likely mediators of the effects of corticoadrenal steroids on behavior. This paper proposes that an imbalance of adrenal steroids and their metabolites may play a fundamental role in the psychophysiopathology of Cushing's and depressive disorders. The imbalance of these hormones, especially at limbic sites, could distort mood and memory content affecting cognition based on recollection and present experiences. Reestablishing an adrenal balance could therefore be considered as a therapeutic aid in a subset of depressive disorders. PMID- 8461284 TI - Anxiety disorder in a case of Arnold-Chiari malformation. AB - This report describes a patient who suffered concurrently from panic disorder with agoraphobia and Arnold-Chiari malformation. Surgical correction of the neuroanatomical anomaly altered the patient's symptom pattern, enabling a more clear delineation of her anxiety disorder. PMID- 8461283 TI - The manic syndrome: factors which may predict a patient's response to lithium, carbamazepine and valproate. AB - Studies suggest that 80% to 90% of all patients in the manic state respond to lithium provided that they are relatively free of dysphoria ("pure mania"). In contrast, less than 40% of individuals in the manic state who cycle rapidly or are substantially dysphoric ("dysphoric mania") respond to lithium. These patients appear to be more responsive to carbamazepine and valproate. The authors conclude that carbamazepine and valproate are the drugs of choice if one desires to treat a rapidly cycling individual or patient with dysphoric mania with just one agent. However, they emphasize that a prospective study designed to identify the predictors of response of primary mania to lithium, carbamazepine and valproate is required. Studies assessing the relative value of lithium, carbamazepine or valproate as prophylactic agents in the care of patients with specific subtypes of mania are also needed. These studies would address the most important issues confronting researchers interested in the drug treatment of mania. PMID- 8461285 TI - Is the routine CT head scan justified for psychiatric patients? A prospective study. AB - Thirty-four psychiatric patients, assessed for a physical illness that was missed during diagnosis, underwent a CT scan. After investigation, the diagnosis of 14 patients changed from a functional to an organic illness. In nine patients, the CT scan was reported to be abnormal, and yet only two were diagnosed as having an organic syndrome. In seven patients, the CT scan was normal but the patients had an undisputed organic brain syndrome. These findings indicate that the use of CT scans should be restricted to cases in which the diagnosis is seriously in question. The clinical findings should dictate the use of CT scans either to clarify or to complement them. PMID- 8461287 TI - Depression and attachment problems. AB - This study investigated the characteristics related to attachment of 42 depressed psychiatric patients and 42 non-depressed psychiatric controls. The depressed subjects demonstrated an anxious pattern of attachment, characterized by either intense care-seeking in relation to their attachment figure or angry withdrawal from their attachment figure when their desire for security was frustrated. The results are discussed in terms of Bowlby's attachment construct. PMID- 8461286 TI - Early onset of lithium-associated hypothyroidism. AB - In general practice, psychiatrists are confronted with the difficulty of structuring a rational design for the early detection of hypothyroidism. To determine the period during which a patient receiving lithium is most at risk of developing hypothyroidism, a retrospective study was conducted on the records of 154 patients at two general hospital lithium clinics from January 1980 to August 1991. Forty-two cases of hypothyroidism (clinical hypothyroidism and/or abnormally elevated levels of TSH) were detected. A significant difference was found between the onset of hypothyroidism and age (older patients developed more thyroid dysfunction), but no significant differences were found between thyroid abnormality and sex or diagnostic category and menopausal status, although trends were observed for the two former variables. This longitudinal study is the first to describe an outline of thyroid functioning in terms of the duration of treatment. Lithium-associated hypothyroidism develops most often during the first two years. Of the 42 cases of hypothyroidism, 16 were diagnosed within six months (38%), 23 within the first year (55%), and 31 two years (74%). Since thyroid functioning is an important parameter in the course of affective disorders, its close and frequent monitoring is mandatory during the first two years of treatment. PMID- 8461288 TI - Distribution of the chlorophyll spectral forms in the chlorophyll-protein complexes of photosystem II antenna. AB - The chlorophyll-protein complexes that form the antenna system of photosystem II have been purified and analyzed in terms of the commonly observed chlorophyll spectral forms. With the exception of chlorophyll b, which is known to be associated with the complexes comprising the outer antenna (LHCII, CP24, CP26, CP29), the spectral forms occur with similar absorption maxima and are present in rather similar amounts in each of the antenna complexes. On the basis of the published chlorophyll stoichiometries for the complexes in photosystem II antenna, the distribution of the spectral forms in a "reconstituted" antenna has been determined. These data were used to calculate the equilibrium population of excited states within the various chlorophyll-protein complexes within photosystem II. This was compared with the light absorption capacity of each of the complexes in the "reconstituted" antenna. The ratio of these two parameters (excited-state equilibrium distribution/absorption capacity) was determined to be 1.21 for the inner (core) antenna and 0.88 for LHCII. The standard free energy change for exciton transfer from the outer to the inner antenna was calculated to be -0.17 kcal mol-1. It is concluded that the photosystem II antenna is arranged as a very shallow funnel. PMID- 8461289 TI - DNA double-crossover molecules. AB - DNA molecules containing two crossover sites between helical domains have been suggested as intermediates in recombination processes involving double-strand breaks. We have modeled these double-crossover structures in an oligonucleotide system. Whereas the relative orientations of the helical domains must be specified in designing these molecules, there are two broad classes of the molecules, the parallel, DP, and antiparallel, DA, molecules. The distance between crossover points must be specified as multiples of half-turns, in order to avoid torsional stress in this system; hence, there are two further subdivisions, those double-crossover molecules separated by odd, O, and even, E, numbers of half-turns. In addition, the parallel molecules with odd numbers of half-turns between crossovers must be divided into those with an excess major or wide-groove separation, W, or those with an excess minor- or narrow-groove separation, N. We have constructed models of all five of these classes, DAE, DAO, DPE, DPOW, and DPON. DPE molecules containing 1 and 2 helical turns between crossovers have been constructed; the DAE molecule contains 1 turn between crossovers, and the DAO, DPOW, and DPON molecules contain 1.5 helical turns between crossovers. None of the parallel molecules is well-behaved; the molecules either dissociate or form multimers when visualized on native polyacrylamide gels. In contrast, antiparallel molecules form single bands when assayed in this fashion. Hydroxyl radical autofootprinting analysis of these molecules reveals protection at expected sites of crossover and of occlusion, suggesting that all the complexes contain linear helix axes that are roughly coplanar between crossovers. However, the DPOW molecule and the DPE molecule with 2 turns between crossovers show decreased protection in the portion between crossovers, suggesting that their helices may bow in response to charge repulsion. We conclude that the helices between parallel double crossovers must be shielded from each other or distorted from linearity if they are to participate in recombination. We have analyzed the possibilities of branch migration and crossover isomerization in double-crossover molecules. Parallel molecules need no sequence symmetry beyond homology to branch migrate, but the sequence symmetry requirements for antiparallel molecules restrict migration to directly repetitive segments that iterate the sequence between crossovers. Crossover isomerization appears to be a very complex process in parallel double-crossover molecules, suggesting that it may be catalyzed by topoisomerases if it occurs within the cell. PMID- 8461290 TI - The specific interactions of HMG 1 and 2 with negatively supercoiled DNA are modulated by their acidic C-terminal domains and involve cysteine residues in their HMG 1/2 boxes. AB - Sedimentation and gel retardation studies show a stronger interaction of HMG 1 and 2 with negatively supercoiled DNA than with linear, nicked-circular, or positively supercoiled ds-DNA. An apparent unwinding angle of 58 degrees was obtained for HMG 1 and 2 when assayed by protection of negatively supercoiled DNA from topoisomerase I relaxation or when assayed by the supercoiling of nicked circular DNA with T4 DNA ligase. The protection of negatively supercoiled DNA was linear up to molar ratios of about 250:1. There was little change in binding reactions or in the protection of supercoiled DNA at ratios above 250:1, indicating that both activities saturate and that HMG 1 and 2 have binding site sizes of about 20 bp. P1, the major tryptic fragment of HMG 1 or 2 which retains the two DNA binding HMG 1/2 boxes, displays a 2-fold increase in binding to all types of ds-DNA compared to intact HMG 1 or 2. However P1 protects negatively supercoiled DNA from topoisomerase I relaxation about 5-fold less than intact HMG 1 or 2. Complete protection with P1 occurs at a molar ratio 1040:1, indicating a DNA binding site size of about 4 bp and an apparent unwinding angle of 10 degrees. P1 binding to closed-circular ss-DNA also involves a binding site of about 4 bp. Adding the acidic C-terminal fragment to P1 reversed its binding and allowed topoisomerase I to relax supercoiled DNA. These findings highlight the importance of the acidic C-terminal domains of HMG 1 and 2 in limiting electrostatic interactions of the HMG 1/2 boxes with ds- or ss-DNA. N Ethylmaleimide inhibited the binding of intact HMG 1 or 2 to negatively supercoiled DNA, but did not inhibit the electrostatic binding of HMG 1 or 2 to ss-DNA, or of P1 to any form of DNA (ds or ss). These results suggest that cysteine residues are involved in the specific interaction of HMG 1 or 2 with negatively supercoiled DNA and that the acidic C-terminal domains modulate an intramolecular conformational change involving sulfhydryls within the HMG 1/2 boxes. PMID- 8461291 TI - 7,8-Dihydro-8-oxoadenine as a replacement for cytosine in the third strand of triple helices. Triplex formation without hypochromicity. AB - Oligonucleotides containing thymine and cytosine (or 5-methylcytosine) bases are known to bind to specific homopurine sequences in double-stranded DNA by means of T.AT and C+.GC base triplets. Cytosine in the third strand of such triple helices can be completely replaced by 7,8-dihydro-8-oxoadenine a base which should not require protonation to form base triplets. Experiments using native PAGE and inhibition of triplex-directed photo-cross-linking demonstrate that triplexes with 7,8-dihydro-8-oxoadenine in the third strand are as stable at pH 6.0 as triplexes with 5-methylcytosine. The stability of triplexes with 7,8-dihydro-8 oxoadenine, unlike those with 5-methylcytosine, is not substantially diminished upon raising the pH to 7.4. Surprisingly, triplex formation with an oligonucleotide containing only thymine and 7,8-dihydro-8-oxoadenine was not associated with significant hypochromicity and could not be detected in conventional thermal denaturation experiments. PMID- 8461292 TI - Effects of site-specific acetylation on omega-conotoxin GVIA binding and function. AB - Chemical modification of omega-conotoxin GVIA (omega-CgTXGVIA) was performed using nonsaturating concentrations of acetic anhydride to generate seven distinct derivatives. Following separation of these peptides using reverse-phase HPLC (RP HPLC), their individual molecular weights were determined using fast bombardment mass spectrometry (FAB-MS). Three peptides contained a single acetylated amino group, three possessed two acetylated amino groups, and the last contained three acetylations. For each peptide, the specific site of acetylation was confirmed using a scheme of tryptic digestion, under nonreducing conditions, followed by RP HPLC and FAB-MS. Biological profiles for each peptide were obtained by analyzing their capacity to displace native 125I-omega-CgTx GVIA binding to rat hippocampal membranes and to block K(+)-stimulated 45Ca2+ influx into chick brain synaptosomes. The data indicate that successive additions of acetyl moieties to omega-CgTx GVIA lead to a loss of both binding affinity and Ca2+ influx inhibitory potency. Within the monoacetylated series, acetylation of the amino terminal of Cys-1, as compared to the epsilon-amino group of either Lys-2 or Lys 24, leads to the greatest shift in potency. In summary, these results indicate that basic (i.e., primary amino) groups, which are brought into close proximity as a result of disulfide bridging, are important in the functional blockade of neuronal Ca2+ channels by omega-CgTx GVIA. PMID- 8461293 TI - Similarities and differences between yeast and vertebrate calmodulin: an examination of the calcium-binding and structural properties of calmodulin from the yeast Saccharomyces cerevisiae. AB - The Ca(2+)-binding and structural properties of calmodulin (CaM) from the yeast Saccharomyces cerevisiae (yCaM) were analyzed by flow dialysis and NMR spectroscopy. Full-length yCaM and two truncated versions of yCaM were expressed in Escherichia coli and purified. yTR1 (residues 1-76) and yTR2 (residues 75-147) are similar to the vertebrate CaM fragments TR1 and TR2, which are generated by limited proteolysis with trypsin. As was found for the fragments of vertebrate CaM, the yCaM fragments retain native conformation and are useful for examining structure and metal-binding properties by NMR. Evidence for a short beta-sheet in each domain, as well as characteristic NOEs to aromatic residues, suggests that yCaM folds similarly to vertebrate CaM. Furthermore, although the previously considered "invariant" glycine at position 6 is replaced by a histidine in site II of yCaM, the far downfield chemical shift of His-61's amide proton suggests that this site adopts a conformation similar to that found in other EF-hand sites. Macroscopic Ca(2+)-binding constants were determined for yCaM by flow dialysis, revealing three high-affinity sites (dissociation constants were 5.2, 3.3, and 2.3 microM in the presence of 1 mM MgCl2 and 100 mM KCl). Positive cooperativity was observed among all sites. Ca2+ binding was also monitored indirectly by one-dimensional NMR. Titrations of the fragment molecules reveal that two binding sites reside in the N-terminal domain (sites I and II) and one in the C-terminal domain (site III). All three sites exhibit slow-exchange behavior in the intact protein, but site III exhibits fast-exchange behavior in the isolated C-terminal domain fragment (yTR2). Thus, an interaction between the two domains of intact yCaM affects the behavior of site III. These results with yCaM differ from those of vertebrate CaM in terms of Ca(2+)-binding stoichiometry, affinity of sites I and II, relative affinity of sites in the N- and C-terminal domains, and the exchange behaviors observed. PMID- 8461294 TI - Divalent cation-induced lipid mixing between phosphatidylserine liposomes studied by stopped-flow fluorescence measurements: effects of temperature, comparison of barium and calcium, and perturbation by DPX. AB - To understand the mechanism of membrane fusion, it is important to study the processes that mix the lipids of two apposed membranes. We measured the rates of divalent cation-induced aggregation and lipid mixing of bovine brain phosphatidylserine (BBPS) LUV, using light scattering and a resonance energy transfer assay. The lipid and divalent cation solutions were combined by stopped flow mixing, which permitted measuring the half-times of aggregation and lipid mixing between pairs of liposomes. The collisional quencher DPX [p-xylene bis(pyridinium bromide)], used in a liposome contents-mixing assay, lowered the main transition temperature (Tm) of BBPS by about 10 degrees C and decreased the temperature threshold for lipid mixing. Since DPX was inside the liposomes for the latter measurements, this implies that perturbations to the inner monolayer affect the reactivity of the liposome. When palmitoyl-oleoyl-PS (POPS) was substituted for BBPS, little or no lipid mixing occurred. Ca(2+)- and Ba(2+) induced BBPS aggregation and lipid mixing were compared as a function of temperature and divalent cation concentration. Aggregation rates were nearly insensitive to temperature and correlated with the percent of PS bound to either Ba2+ or Ca2+. Above Tm, lipid-mixing rates increased with the Ba2+ and Ca2+ concentrations and temperature, even above the Tm of the Ba2+/PS complex. Arrhenius plots were linear for both ions. The temperature dependence was greater for Ca(2+)- than Ba(2+)-induced reactions, and the slopes were independent of divalent cation concentration. When equivalent fractions of PS were bound with divalent cation at, and above, 20 degrees C, the lipid-mixing rate was greater with Ca2+ than with Ba2+. The faster rate may reflect greater activation entropies and/or greater attempt frequencies at one or more steps in the Ca(2+) induced process. We conclude that stopped-flow mixing permits better characterization of initial interaction between liposomes, that small changes in the acyl chain region of the PS bilayer or the inner monolayer can have large effects on lipid-mixing rates, and that the differences between Ba(2+)- and Ca(2+)-induced interactions may be related to qualitative differences in the destabilization step. PMID- 8461295 TI - pH- and ionic strength-dependent fusion of phospholipid vesicles induced by pardaxin analogues or by mixtures of charge-reversed peptides. AB - The fusogenic properties of the neurotoxin paradaxin and eight of its analogues with small unilamellar vesicles (SUV), composed of egg phosphatidylcholine and phosphatidylserine (PC/PS), were investigated. Fusion was demonstrated by a lipid mixing assay and by an increase in vesicle size as revealed by electron microscopy. The lipid-mixing assay was performed at either neutral (pH 6.8) or acidic (pH 4.5) conditions, in solutions containing either high or low salt concentrations. A low level of fusion could be induced at neutral pH only by pardaxin derivatives with amino groups at both the peptide's backbone and N terminus. However, a marked enhancement in the fusogenic activity occurred when amino groups were present also in the C-terminus. Pardaxin analogues in which amino groups were substituted by carboxylic groups induced elevated levels of fusion only at high salt concentrations where enhancement of aggregation occurs, and acidic pH, which increased alpha-helicity. The influence of mutual interactions between pardaxin's analogues possessing complementary charges on the lipid-mixing process was also studied. At neutral pH and high salt, an inactive acidic analogue increased the fusogenic activity of a complementary-charged basic peptide. However, such mutual interactions at low salt concentrations reduced the fusogenic activity of the pardaxin analogues. Analogues containing D-amino acids were not fusogenic, thus demonstrating the structural specificity of these observations. The results indicate that the charge, alpha-helical structure, and aggregation of peptide monomers play an important role in the fusogenic ability of polypeptides. PMID- 8461296 TI - Two structurally related diaziridinylbenzoquinones preferentially cross-link DNA at different sites upon reduction with DT-diaphorase. AB - The nucleotide sequence preferences for the formation of interstrand cross-links induced in DNA by 2,5-diaziridinyl-1,4-benzoquinone (DZQ) and 3,6-dimethyl-2,5 diaziridinyl-1,4-benzoquinone (MeDZQ) were studied using synthetic duplex oligonucleotides and denaturing polyacrylamide gel electrophoresis (PAGE). Reaction of these bifunctional alkylating agents with a DNA duplex containing several potential cross-linking sites resulted in the formation of cross-linked DNAs with different electrophoretic mobilities. Analysis of the principal cross linked products by piperidine fragmentation revealed that the preferential site of cross-linking was altered from a 5'-GNC to a 5'-GC sequence upon reduction of DZQ to the hydroquinone form by the enzyme DT-diaphorase. In contrast, the reduced form of MeDZQ was found to preferentially cross-link at 5'-GNC sites within the same sequence. These preferences were confirmed in duplex oligonucleotides containing single potential cross-linking sites. Additional minor cross-linked products were characterized and revealed that DZQ and MeDZQ are both capable of cross-linking across four base pairs in a 5'-GNNC sequence. PMID- 8461297 TI - A quantum mechanical study of the active site of aspartic proteinases. AB - We have performed ab initio self-consistent field (SCF) and configuration interaction (CI) calculations on the active site of the aspartic proteinases pepsin and endothiapepsin. The active site, which carries a formal negative charge to effect hydrolysis, was modeled as a formic acid/formate anion moiety and a water molecule, and the nearest hydrogen bonding residues (Gly34, Ser35, Gly217, and Thr218, with respect to the residue numbering in endothiapepsin) were modeled as formamide and methanol molecules. Four possible binding modes for the active-site water molecule were considered. In contrast to previous theoretical studies, we predict that the most stable form has the water molecule forming a bifurcated hydrogen bond to the inner oxygens of Asp32 and -215, with Asp32 being ionized. The calculations suggest that the water molecule prefers to bind across the shortest OD32 ... OD215 diagonal of the active-site carboxyl groups and therefore the binding mode of the water molecule for all the native aspartic proteinases can be readily predicted by measuring these distances. PMID- 8461298 TI - Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis. AB - Amino acid sequence comparisons reveal that tyrosine-152 and lysine-156 of Drosophila alcohol dehydrogenase (ADH) are conserved in homologous dehydrogenases, suggesting that these residues are important in catalysis. To test this hypothesis, we used site-directed mutagenesis to substitute tyrosine 152 with phenylalanine, histidine, or glutamic acid or to substitute lysine-156 with isoleucine. All of these mutants are catalytically inactive. Two mutants were active: A cysteine mutation of tyrosine-152 has 0.25% of wild-type ADH activity, while an arginine substitution of lysine-156 retains 2.2% of wild-type ADH activity. Kinetic analysis shows that the cysteine mutant increases Km(ethanol) 56-fold and Km(propan-2-ol) 100-fold, while Km(NAD) values are essentially unaltered. The arginine mutant also shows the significant enlargement of Km(ethanol), but not of Km(NAD). Furthermore, the cysteine mutant and arginine mutant have different substrate specificity and behave differently on competitive inhibition than wild-type ADH. These results suggest that both tyrosine-152 and lysine-156 have essential roles in catalysis by Drosophila ADH. PMID- 8461299 TI - Novel ion specificity of a carboxylate cluster Mg(II) binding site: strong charge selectivity and weak size selectivity. AB - Carboxylate cluster Mg(II) binding sites consist of a cluster of side-chain carboxylates, typically 3-4 in number, partially buried in a shallow cleft on the surface of a Mg(II) binding protein. Such clusters are often found in the active sites of enzymes catalyzing phosphochemistry. An example is the phospho-signaling protein CheY of the Escherichia coli chemotaxis pathway, which binds Mg(II) via a cluster of three carboxylates at its phosphorylation site. The present study quantitates both the ion charge and size specificity of the CheY site by measuring the dissociation constants of metal ions from groups Ia, IIa, IIIa, and the lanthanides; these spherical cations provide a range of substrates with incrementally varying charge and radius. The site binds divalent and trivalent cations, but it effectively excludes monovalent cations, including the physiological ions Na(I) and K(I). This charge specificity is in contrast to the site's remarkable lack of size specificity: divalent and trivalent cations exhibit affinities which are essentially independent of radius. It is revealing to compare the ion specificity of the Mg(II) site with the previously characterized specificity of the EF-hand class of Ca(II) sites commonly found in Ca(II) signaling proteins. The Mg(II) and Ca(II) sites exhibit similar charge selectivity, but the Ca(II) site is highly size-selective, preferring divalent and trivalent ions with radii similar to that of Ca(II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461300 TI - Thioltransferase is a specific glutathionyl mixed disulfide oxidoreductase. AB - To study the substrate specificity and mechanism of thioltransferase (TTase) catalysis, we have used 14C- and 35S-radiolabeled mixed disulfides of cysteine and glutathione (GSH) with various cysteine-containing proteins. These protein mixed disulfide substrates were incubated with glutathione, glutathione disulfide (GSSG) reductase, and NADPH in the presence or absence of thioltransferase. Glutathione-dependent reduction of protein mixed disulfides was monitored both by release of trichloroacetic acid soluble radiolabel and by formation of GSSG in an NADPH-linked spectrophotometric assay. GSH-dependent dethiolation of [35S]glutathione-papain mixed disulfide (papain-SSG) and the corresponding bovine serum albumin mixed disulfide (BSA-SSG) were catalyzed by thioltransferase (from human red blood cells) as shown by the radiolabel assay, and equivalent rates were measured by the spectrophotometric assay. Dethiolation of [35S]hemoglobin glutathione mixed disulfide (Hb-SSG) was also catalyzed by TTase. In contrast, TTase did not catalyze GSH-dependent dethiolation of [14C]papain-SScysteine or [14C]BSA-SScysteine as measured by the radiolabel assay. [14C]Hb-SScysteine and Hb-SScysteamine also did not serve as substrates. In separate experiments, TTase from rat liver displayed analogous selectivity. Thus, thioltransferase (glutaredoxin) appears to be specific for glutathione-containing mixed disulfides. Apparent TTase catalysis of GSSG formation from the papain- and BSA SScysteine mixed disulfides was observed by the spectrophotometric assay, but a lag phase occurred consistent with preenzymatic formation of GSScysteine which could serve as the actual TTase substrate. Two-substrate kinetic studies of TTase with GSH and GSScysteine gave patterns of parallel lines on double-reciprocal plots (1/V vs 1/[S]), consistent with a simple ping-pong mechanism involving a TTase-SSG intermediate. PMID- 8461301 TI - Proton nuclear magnetic resonance sequential assignments and secondary structure of an immunoglobulin light chain-binding domain of protein L. AB - The 1H NMR assignments have been made for the immunoglobulin (Ig) light chain binding B1 domain of protein L from Peptostreptococcus magnus. The secondary structure elements and the global folding pattern were determined from nuclear Overhauser effects, backbone coupling constants, and slowly exchanging amide protons. The B1 domain was found to be folded into a globular unit of 61 amino acid residues, preceded by a 15 amino acid long disordered N-terminus. The folded portion of the molecule contains a four-stranded beta-sheet spanned by a central alpha-helix. The fold is similar to the IgG-binding domains of streptococcal protein G, despite the fact that the binding sites on immunoglobulins for the two proteins are different; protein G binds IgG through the constant (Fc) part of the heavy chain, whereas protein L has affinity for the variable domain of Ig light chains. PMID- 8461302 TI - Oxalate- and Ga(3+)-induced structural changes in human serum transferrin and its recombinant N-lobe. 1H NMR detection of preferential C-lobe Ga3+ binding. AB - (1) The binding of the synergistic anion oxalate and Ga3+ to human serum transferrin (HTF, 80 kDa) and its recombinant N-lobe (HTF/2N, 40 kDa) has been studied by one- and two-dimensional 1H NMR spectroscopy, at 310 K, pH*7.25. (2) Specific protein resonances are sensitive to oxalate binding (fast exchange on the NMR time scale) and allowed determination of the apparent binding constant for oxalate binding to the N-lobe (log K 4.04). (3) Slow exchange between apo-HTF and Ga-loaded HTF or HTF/2N was observed. Binding of Ga3+ appeared to be accompanied by small changes in the orientations of residues in hydrophobic pockets in the interdomain hinge region close to the metal binding site. (4) Under the conditions used, preferential binding of Ga3+ (added as Ga(NTA)2) to the C-lobe of HTF was observed. Binding to the C-lobe markedly perturbed resonances in the glycan N-acetyl region of the spectrum, suggesting that metal binding is communicated to the surface of the protein. This could be important in receptor recognition of metallotransferrins. (5) The displacement of Ga3+ from Ga ox-HTF with Fe3+ was studied, and the paramagnetic broadening effects allowed identification of resonances from groups close to Fe3+. The passage of Fe3+ from the exterior to the interior of the protein was followed by 1H NMR spectroscopy, and the half-life for Ga(3+)-Fe3+ exchange was determined to be 4.3 h (310 K). PMID- 8461303 TI - Design of a linker for trivalent thrombin inhibitors: interaction of the main chain of the linker with thrombin. AB - N alpha-Acetyl[D-Phe45,Arg47]hirudin45-65 (P53) is a bivalent thrombin inhibitor (Ki = 5.6 nM) that consists of an active site inhibitor segment, [N alpha-acetyl (dF)PRP]; a fibrinogen recognition exo site inhibitor segment, hirudin55-65 (DFEEIPEEYLQ-OH); and a linker, hirudin49-54 (QSHNDG), connecting these inhibitor segments (DiMaio et al., 1990). The structure-function relationships of the linker were studied using a combination of various omega-amino acids, which modified the length of the linker as well as the number and the locations of peptide bonds. Linkers with 14-18 atoms (counting only the atoms contributing to the length of the linker) showed a competitive inhibition with Ki = 1.7-3.4 nM. The potency of the inhibitors with 12-13-atom linkers was sensitive to the chemical structure of the linker. The high-potency inhibitors showed a competitive inhibition, while the low-potency inhibitors showed a hyperbolic inhibition. Among them, an inhibitor with a 13-atom linker showed the highest potency (Ki = 0.51 nM, an 11-fold improvement from that of P53 above), indicating that this is an optimal linker length. Since linkers with 6-10 atoms failed to bridge the active site and exo site inhibitor segments, a minimum of 11 atoms was required to bridge them, even though the potency of the inhibitor with an 11-atom linker was weak (Ki = 26 nM). Molecular dynamics simulation of the inhibitors with 13-atom linkers suggested that some linkers serve as a functional domain with the amide bond of the linker interacting with thrombin through hydrogen bonds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461304 TI - Thermodynamics of tubulin polymerization into zinc sheets: assembly is not regulated by GTP hydrolysis. AB - The thermodynamics of tubulin assembly into Zn sheets have been studied, with special emphasis on the role of bound nucleotide and of GTP hydrolysis in polymerization. In contrast to microtubules, Zn sheets could be assembled from GDP-tubulin as well as from GTP-tubulin. Accordingly, no appreciable destabilization of the Zn sheets was observed following GTP hydrolysis and P(i) release, indicating that the binding of Zn2+ to tubulin has abolished the regulatory switch role played by GTP hydrolysis in tubulin assembly. As a consequence, the critical concentration for assembly of Zn sheets did not increase with tubulin concentration, a feature characteristic of microtubule assembly. Zn sheets do not bind P(i) analogs, indicating that the gamma-phosphate binding locus of the E-site of tubulin is occluded following GTP hydrolysis in these GDP-tubulin polymers. Nonlinear van't Hoff plots were obtained for assembly of Zn sheets in the presence of either GTP or GDP, consistent with a change in heat capacity. Enthalpy, entropy, and heat capacity changes had values similar to those reported for assembly of microtubules or polymerization of tubulin colchicine, indicating that hydrophobic tubulin-tubulin interactions are of comparable size in these different polymers. PMID- 8461305 TI - Structure and dynamics of sialic acid at the surface of a magnetically oriented membrane system. AB - A structural analysis of a sialic acid containing glycolipid alpha-dodecyl-N acetylneuraminic acid anchored to the surface of a phospholipid-based membrane like fragment is presented. The analysis is based on measurement of dipolar interactions between 13C-13C and 13C-1H spin pairs in a magnetically oriented membrane phase and the interpretation of data using an order matrix formalism. Structural analysis in this medium allows an assessment of properties in an environment approximating the environment where similar molecules function as cell surface receptors. The results indicate an extended headgroup conformation with the carboxyl group of the sialic acid near the membrane interface. Anisotropic motion of the sialic acid headgroup occurs with the most restriction along an axis which is significantly out of the plane of the sialic acid ring suggesting an important role for the carboxylate group in membrane surface interaction. The effect of calcium on the headgroup orientation was also investigated, but the results showed no significant change in the preferred conformation, possibly due to a weak binding under the conditions of the experiment. PMID- 8461306 TI - Purification and further characterization of macrophage 70-kDa protein, a calcium regulated, actin-binding protein identical to L-plastin. AB - We have previously identified a macrophage 70-kDa, actin-bundling protein as a constituent of actin-based cytoplasmic gel and showed that its association with or dissociation from cytoplasmic gels was remarkably affected by submicromolar calcium. In this study, we purified the 70-kDa protein from soluble cytosolic extracts and carried out a more detailed characterization. The amino acid sequences of four peptidic fragments, obtained from the purified protein by enzymatic or chemical cleavage, were completely or nearly identical to those of L plastin, a protein initially identified in transformed cells from solid tumors (Goldstein & Leavitt, 1985). By Western blot analysis of normal cells and tissues using specific anti-70-kDa protein antibodies, the 70-kDa molecule was detected only in hematopoietic cells. The 70-kDa protein bound to actin with apparent Kd values of 1.8 and 5.5 microM in the absence and presence of 20 microM free calcium, respectively. Cross-linking activity measured by falling-ball viscosimetry was optimal at free calcium lower than 0.15 microM but was progressively inhibited at higher calcium concentrations, within the physiological range. Half-maximal inhibition occurred at 1.6 microM free calcium. No severing of actin filaments by the 70-kDa protein was observed in any of these assays or previously (Pacaud & Harricane, 1987). Major conformational changes of the protein, as measured by the fluorescence emission intensity of tyrosine residues, occurred at free calcium concentration ranging between 0.15 and 1.5 microM. Magnesium did not mimic the calcium effect. The results suggest that the 70-kDa protein possesses both high-affinity sites and selectivity for calcium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461307 TI - 1H-NMR resonance assignments, secondary structure, and global fold of the TR1C fragment of turkey skeletal troponin C in the calcium-free state. AB - The TR1C fragment of turkey skeletal muscle TnC (residues 12-87) comprises the two regulatory calcium binding sites of the protein. Complete assignments of the 1H-NMR resonances of the backbone and amino acid side chains of this domain in the absence of metal ions have been obtained using 2D 1H-NMR techniques. Sequential (i,i+1) and short-range (i,i+3) NOE connectivities define two helix loop-helix calcium binding motifs, and long-range NOE connectivities indicate a short two-stranded beta-sheet formed between the two calcium binding loops. The two calcium binding sites are different in secondary structure. In terms of helix length, site II conforms to a standard "EF-hand" motif with the first helix ending one residue before the first calcium ligand and the second helix starting one residue after the beta-sheet. In site I, the first helix ends three residues before the first calcium ligand, and the second helix starts three residues after the beta-sheet. A number of long-range NOE connectivities between the helices define their relative orientation and indicate formation of a hydrophobic core between helices A, B, and D. The secondary structure and global fold of the TR1C fragment in solution in the calcium-free state are therefore very similar to those of the corresponding region in the crystal structure of turkey skeletal TnC [Herzberg, O., & James, M.N.G. (1988) J. Mol. Biol. 203, 761-779]. PMID- 8461308 TI - 1H NMR spectroscopic studies of selenosubtilisin. AB - Anomalously low-field signals in 1H NMR spectra of serine proteases provide valuable information on the protonation state of the catalytic histidine residue. We have examined the pH dependence of the deshielded protons of three different oxidation states of selenosubtilisin, a semisynthetic selenoenzyme with significant peroxidase activity, in order to evaluate the influence of the selenium prosthetic group on the hydrogen-bonding network in the modified active site. In the spectra of the anionic seleninate and selenolate derivatives, two resonances were observed at 18.0 and 15.5/14.0 ppm, assigned respectively to the N delta 1 and N epsilon 2 protons of protonated His64. These signals were apparent from pH 4 to above pH 10, indicating that the negatively charged prosthetic group increases the stability of the imidazolium dramatically, raising its pKa by at least 3-4 pH units. In contrast, a neutral selenenyl sulfide species exhibits no deshielded proton signals at 18 ppm at any pH but has a weak signal at 14.1 ppm above pH 7 which was assigned to the N delta 1 imidazole proton of neutral His64. While the pKa of His64 appears normal (approximately 7) in this derivative, the selenenyl sulfide substitution may alter the orientation of the imidazole ring within the active site for steric reasons. Together with data on the influence of pH on peroxidase activity, these results suggest that selenosubtilisin's His64 acts as a general acid facilitating the reduction of the selenenyl sulfide to selenolate by thiols. PMID- 8461309 TI - How do mutations at phenylalanine-153 and isoleucine-155 partially suppress the effects of the aspartate-27-->serine mutation in Escherichia coli dihydrofolate reductase? AB - Several second-site suppressors of the D27S lesion in Escherichia coli dihydrofolate reductase (DHFR) have been identified. The activity of the primary mutant, D27S DHRF, was found to be greatly decreased at pH 7.0, consistent with aspartic acid-27 being critically involved in proton donation during catalysis. Partial suppressors of the D27S mutation have been selected by their ability to confer an increased resistance to trimethoprim upon host E. coli; the suppressors have been identified as F153S or I155N substitutions. D27S+F153S and D27S+I155N DHFRs display 2-3-fold increases in kcat over D27S DHFR values, but only the F153S mutation decreases the Km for dihydrofolate by a factor of 2. Neither double mutant approaches wild-type DHFR activity. Unexpectedly, Phe153 and Ile155 occur on the surface of the protein and are approximately 8 and 14 A distant from the active site. Ile155 is a member of a beta-bulge. A previously identified suppressing mutation, F137S, occurs nearby and is also a member of the same beta bulge [Howell et al. (1990) Biochemistry 29, 8561-8569]. Clustering of these three second-site mutations indicates this area of the structure may be important in protein function. Conformational changes due to the presence of these suppressing mutations are likely as the F153S and I155N mutations do not affect hydride-transfer rates upon introduction in wild-type DHFR and alterations in circular dichroism spectra are associated with the double-mutant DHFRs. PMID- 8461311 TI - Mutations designed to modify the environment of the primary electron donor of the reaction center from Rhodobacter sphaeroides: phenylalanine to leucine at L167 and histidine to phenylalanine at L168. AB - Two mutations, L168 His to Phe and L167 Phe to Leu, were made in residues near the primary electron donor, a bacteriochlorophyll dimer, of the reaction center from Rhodobacter sphaeroides. Blue shifts of 10-15 nm in the 865-nm band of the donor were observed in the optical absorption spectra of both of the mutant reaction centers. The rate of initial electron transfer was determined by measurement of the kinetics of the decay of the excited state of the donor, and the rate of charge recombination was determined by measurement of the recovery of the bleaching of the donor. The initial electron transfer time constant and the charge recombination time constant were determined to be 3.6 ps and 220 ms, respectively, in the L168 His to Phe mutant and 5.0 ps and 85 ms in the L167 Phe to Leu mutant, compared to 3.8 ps and 100 ms measured for the wild type. The oxidation potential of the donor measured by oxidation-reduction titrations was found to decrease by 80 mV in the L168 His to Phe mutant and increase by 25 mV in the L167 Phe to Leu mutant. Time-resolved fluorescence decay measurements indicated that the change in the oxidation potential of the donor in the L168 His to Phe mutant resulted in a change in the energies of the charge-separated states. The results show that an increase in the driving force does not increase the rate of the initial electron transfer reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461310 TI - A transforming growth factor-alpha-Pseudomonas exotoxin hybrid protein undergoes pH-dependent conformational changes conducive to membrane interaction. AB - TP40 is a chimeric protein containing transforming growth factor alpha (TGF alpha) at the N-terminus and a derivative of a 40,000-Da segment (PE40 delta cys) of Pseudomonas exotoxin (PE). PE40 delta cys contains domains Ib, II, and III of PE in which the cysteines are mutated to alanines. The rationale for inclusion of TGF-alpha is to provide TP40 with selective targeting toward cells expressing the epidermal growth factor receptor (EGFr) on their surface [Pastan, I., & FitzGerald, D. (1989) J. Biol. Chem. 264, 15157-15160]. Translocation across endosomal membranes is thought to be a required step for cytotoxic activity of PE. This step is presumably facilitated by the low pH in endosomes which induces exposure of a hydrophobic surface of the protein, which in turn becomes available to interact with and translocate across the membrane. We have employed the hydrophobic fluorescence probe 2-p-toludinylnaphthalene-6-sulfonate (TNS) and the intrinsic tryptophan fluorophores of TP40 to investigate pH-induced changes in the tertiary structure of this protein. The pH dependence of TP40 interaction with liposomes also provided a model for studying protein-membrane interactions. TNS fluorescence was markedly enhanced in the presence of TP40 below pH 4 and to a lesser degree between pH 7 and 5. A progressive red shift of tryptophan fluorescence with decreasing pH was also seen with the approximate midpoint for this transition occurring around pH 3. Both observations suggest that acidic pH induces exposure of hydrophobic regions of TP40, making them accessible to solvent and TNS. No major alteration of the secondary structure was manifested in the far-UV CD spectrum of TP40 upon a reduction in pH from 7 to 2. Thus, the low pH-induced structural change of TP40 appears to involve a subtle exposure of one or more hydrophobic surfaces without an extensive unfolding of the protein's secondary structure. In the presence of anionic liposomes, a low-pH-induced blue shift of the TP40 tryptophan fluorescence was observed, suggesting that interaction with liposomes also required the low-pH conformation of the protein. However, the midpoint of this fluorescence blue shift occurred at approximately pH 5, which is presumably closer to the physiological pH within endosomes. Neutral liposomes failed to induce these spectral changes in TP40, implying a lack of interaction with these lipids. At acidic pH values between 2 and 4, self association of TP40 in solution was detected by equilibrium sedimentation and quasielastic light scattering measurements. This probably results from intermolecular interaction between exposed hydrophobic surfaces.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8461312 TI - Dietary vitamin E reverses the effects of ultraviolet light irradiation on rat skin glycosaminoglycans. AB - Chondroitin 4-sulfate (Ch 4-S), three dermatan sulfates (DS18, DS45a, DS45b) and hyaluronic acid (HA) were the major glycosaminoglycans (GAG) isolated from the skin of 4 groups of albino rats. The yields from Group 1 (control) were: Ch 4-S, 0.015%; HA, 0.028% and DS (total), 0.098% (w/w). Traces of heparin were detected only in rats irradiated with ultraviolet (UV) light (Group II), in the GAG pool isolated with 45% ethanol. Yields increased by at least 28% (w/w) in Group II, but decreased, except HA's, also by at least 28%, below the level of the control, in irradiated rats that also ingested vitamin E (Group III). The sulfate composition of these GAG determined by infrared spectroscopy was as follows: approx. 17% (w/w) for DS18, 21-30% for DS45a, 21-35% for DS45b and 26-44% for Ch 4-S. A 60-70% (mol/mol) N-acetylation of hexosamine in DS45 was estimated by Fourier transform 1H-NMR spectroscopy; the IdUA composition of this DS was 30-46% (mol/mol), and the uronic acid/hexosamine ratio ranged from 2.50:1 to 1.6:1. The data show UV light irradiation of rat skin to result in an abnormally elevated production of the major GAG and oversulfation of Ch 4-S and DS. These effects are reversed, except for the sulfation of DS45b, when the irradiated animals also ingest vitamin E. PMID- 8461313 TI - The acute phase reactant serum amyloid A (SAA3) is a novel substrate for degradation by the metalloproteinases collagenase and stromelysin. AB - We found that the matrix metalloproteinases collagenase (MMP-1) and stromelysin (MMP-3) each has the ability to degrade a novel substrate, serum amyloid A (SAA3). SAA3 is a product of rabbit synovial fibroblasts stimulated with phorbol esters or interleukin-1, and it acts in an autocrine or paracrine manner to induce collagenase in both rabbit and human fibroblasts. Recombinant rabbit fibroblast procollagenase and human fibroblast prostromelysin were produced by baby hamster kidney (BHK) cells stably transfected with these genes, and latent enzyme was activated with aminophenylmercuric acetate (APMA). The Km for both enzymes was approximately 10 microM, and the Vmax for collagenase was approximately 6 pmol/minute/100 ng enzyme, while that for stromelysin was about 3 fold faster. Treatment of SAA3 with either enzyme generated a fragment of approx. 6 kDa that has the same amino terminus as the parent molecule, but this fragment was rapidly degraded. We have been unable to isolate C-terminal fragments, suggesting that the mature protein is cleaved at multiple sites and/or that the initial cleavage fragment is readily digested. The amino acid composition of the 6 kDa fragment suggests that the 14 kDa protein is cleaved at residues 50-57, a hydrophobic region that is conserved between rabbit SAA3 and human SAA1. We conclude that the ability of collagenase and stromelysin to degrade SAA3 broadens the repertoire of substrates for these matrix degrading enzymes, and we speculate that the presence of a feedback mechanism that can subvert the autocrine/paracrine stimulation of matrix-degrading enzymes may play a role in limiting matrix degradation during inflammatory conditions. PMID- 8461314 TI - Isolation and characterization of a sialic acid-specific binding lectin from the hemolymph of Asian horseshoe crab, Tachypleus tridentatus. AB - A lectin was isolated from the hemolymph of Asian horseshoe crab Tachypleus tridentatus by using glycophorin HA affinity chromatography and Sephacryl S-300 gel filtration. The lectin's molecular weight was approx. 533 kDa; being a simple protein comprised of two non-identical subunits with molecular weights of 30 and 32 kDa. The hemagglutinating activity of the lectin against equine erythrocytes was strongly inhibited by several sialoglycoproteins and weakly inhibited by sialic acid, although not inhibited by neutral sugars, hexosamines, N acetylhexosamines, glucuronic acid, or several asialoglycoproteins. In addition, glycophorin HA was more effective than glycophorin HA digested with trypsin in inhibiting hemagglutination of the lectin. These results suggest that the purified lectin specifically reacts with sialic acids containing glycoprotein. PMID- 8461315 TI - Role of the trehalose carrier in dehydration resistance of Saccharomyces cerevisiae. AB - Yeast cells are well known for their ability to survive complete dehydration, a phenomenon that is directly linked to the presence of the sugar trehalose in these cells. This sugar apparently endows the cells with the capacity to survive dehydration. Previous studies on in vitro models showed that trehalose must be present on both sides of the bilayer to stabilize dry membranes. The present report demonstrates that a specific trehalose carrier seems to enable the sugar to protect the yeast cell membrane by translocating trehalose from the cytosol to the extracellular environment. Saccharomyces cerevisiae mutant strains which lack the trehalose carrier did not survive after dehydration although they accumulated endogenous trehalose. Furthermore, when carrier mutants were dehydrated in the presence of exogenous trehalose the cells became more resistant showing increased survival. PMID- 8461316 TI - Irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by H2O2. AB - A concentration-dependent inactivation of 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase was found on preincubation of rat liver microsomal preparations with H2O2 and at lower concentrations in the presence of KCN which inhibited the contaminating catalase. The inactivation was not affected in the presence quenchers of hydroxyl radicals and singlet oxygen and was also obtained when H2O2 was added during the reaction. HMG-CoA, but not NADPH, partially protected the enzyme from H2O2-inactivation. Even at high concentration DTT was unable to reverse this inactivation. The soluble 50 kDa-enzyme was similarly inactivated by H2O2, and the tryptic-digest of the inactivated protein indicated the presence of a disulfide-containing peptide. The results support the view that H2O2 by directly acting on the catalytic domain possibly converts an active thiol group to an inaccessible disulfide and irreversibly inactivates HMG-CoA reductase. PMID- 8461317 TI - Does lung NAD(P)H:quinone reductase (DT-diaphorase) play an antioxidant enzyme role in protection from hyperoxia? AB - NAD(P)H:quinone reductase, or DT-diaphorase, has been studied primarily in the liver where it appears to function as an antioxidant-like enzyme in the 2 electron reduction of some quinones to less toxic hydroquinones. This property together with new molecular biology evidence that oxidants such as H2O2 can induce gene transcription of DT-diaphorase provide especially intriguing reasons to examine the possibility that lung DT-diaphorase could have an important antioxidant enzyme role versus pulmonary O2 toxicity during exposure to hyperoxia. We found that similar to the 'classical' lung antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) DT-diaphorase activity increased significantly in the late gestational fetal lung; also its activity was altered in the same way as the antioxidant enzymes by prenatal hormonal treatment. Another similarity is that DT-diaphorase activity was induced in the neonatal animal lung during hyperoxia, but not in the adult animal lung. However, using various drug treatments which markedly increased lung DT diaphorase activity (e.g., 3-methylcholanthrene, butylated hydroxyanisole, methimazole) we found no improved hyperoxic survival in the treated adult rats. Also, dicumarol treatment, which markedly depressed DT-diaphorase activity, did not diminish the hyperoxic survival rate in an O2-tolerant adult rat model. Thus, we conclude that unlike the classical antioxidant enzymes, increased pulmonary DT diaphorase activity is probably neither necessary nor sufficient to protect against pulmonary O2 toxicity during hyperoxia. PMID- 8461318 TI - The glycosides of hydroxylysine are final products of collagen degradation in humans. AB - Glucosyl-galactosyl-hydroxylysine (GGHYL) and galactosyl-hydroxylysine (GHYL) are metabolites derived from collagen degradation. They are useful biochemical markers provided they are not further processed. Experiments were run to test the activity of alpha- and beta-glycosidases in human kidney cortex preparations. Results allow to exclude the presence of the specific enzymes, in contrast with what is reported for the rat kidney tissue. PMID- 8461319 TI - Persistent decrease in spermidine/spermine N1-acetyltransferase activity in 'post regeneration' rat liver. AB - The activity of cytosolic spermidine/spermine N1-acetyltransferase and polyamine levels were measured in livers of rats killed at different times after partial hepatectomy. The enzyme activity, which showed an early increase a few hours after the operation, had significantly and persistently decreased by the time the liver mass had been regained (10 days) compared to intact rats or sham-operated rats, and up to 30 days after partial hepatectomy, compared to intact rats of the same age. The early induction of spermidine/spermine N1-acetyltransferase activity was also confirmed by the high level of N1-acetylspermidine, which normally is undetectable, and by a dramatic increase in putrescine content. Spermidine levels were increased during the first 10 days after partial hepatectomy, i.e., when the liver had regained its mass, and progressively decreased after this time until 30 days after the operation. The changes in spermine content were similar but not as marked as the changes in spermidine content at the different observation times. PMID- 8461320 TI - Interaction between neutrophil-derived elastase and reactive oxygen species in cartilage degradation. AB - The role of proteases and reactive oxygen species (ROS) in polymorphonuclear neutrophil (PMN) induced cartilage degradation in vitro were studied. ONO-5046, a novel synthetic elastase inhibitor, significantly and dose dependently protected cartilage from degradation induced by PMNs stimulated with phorbol myristate acetate (PMA), opsonized zymosan, N-formyl-methionyl-leucyl-phenylalanine plus cytochalasin-B, or A-23187. The degradation by PMA-stimulated PMNs was unaffected by protease inhibitors which lack anti-elastase activity. However, the hydrogen peroxide (H2O2) reducing agent catalase afforded significant protection. Measurement of elastase activity following PMN activation by PMA showed that antioxidants which reduce H2O2 and/or hypochlorous acid decreased elastase activity. Thus, it is suggested that an indirect interaction between ROS and elastase activity may exist in PMN induced cartilage degradation. Furthermore, the possible implication of an endogenous elastase inhibitor(s) is discussed. PMID- 8461321 TI - Effects of seven months' exposure to a static 0.2 T magnetic field on growth and glycolytic activity of human gingival fibroblasts. AB - Human gingival fibroblasts in confluent cultures were continuously exposed to a static 0.2 T magnetic field for 6 or 8 months. Culture flasks were not changed during the exposure, but culture medium was renewed. After dilution and mixing of the cultures surviving intact, field-exposed and sham-exposed cultures received further field- or sham-exposure on Sm-Co blocks. Rate of cell proliferation, histogram of the nuclear DNA content, rates of lactate production and glucose consumption and the ATP content were determined and cell morphology was investigated by both light- and electron-microscopy. Results show no marked differences between exposed and control cells. PMID- 8461322 TI - In vitro and ex vivo xanthine oxidoreductase activity in rat and guinea-pig hearts using hypoxanthine or xanthine as substrate. AB - Through oxyradical formation xanthine oxidoreductase (XOD) could play a role in the etiology of cardiac damage. Its measurement poses problems, due to little substrate specificity, self-inactivation and endogenous inhibitors. Perfusion of guinea-pig hearts with hypoxanthine gave rise to only little xanthine release; in contrast rat hearts showed vivid xanthine production. Therefore, xanthine breakdown was hypothesized to exceed its formation in guinea-pig hearts. The kinetics of both substrates for XOD in cardiac homogenates were therefore compared with those obtained in perfused hearts. Oxypurine contents and effluent catabolites were determined by HPLC. Regardless of substrate, Vmax values in homogenates were about 38 and 13 mU/g for rat and guinea-pig heart, respectively. Km values were in the 3-5 microM range; therefore the hypothesis concerning the low xanthine release in guinea-pig hearts must be rejected. Activities in hearts perfused with hypoxanthine (50 microM) were 40 and 18 mU/g for rat and guinea pig, respectively; perfusion with xanthine produced < 50% of the activities observed with hypoxanthine (p < 0.002). Intracellular xanthine concentration, estimated from sorbitol distribution space and myocardial xanthine content was negative in both species, contrasting intracellular hypoxanthine levels, which approached extracellular concentrations. This disparate distribution indicates that hypoxanthine transport across the cell membrane far exceeds that of xanthine. Consequently, hypoxanthine is preferable to xanthine as substrate in perfused hearts to estimate XOD activity in situ. PMID- 8461323 TI - Alpha-1,4-glucan lyase, a new class of starch/glycogen degrading enzyme. I. Efficient purification and characterization from red seaweeds. AB - This study presents the first purification and characterization of an alpha-1,4 glucan lyase. The enzyme degraded alpha-1,4-glucan to produce 1,5 anhydrofructose. A simple and efficient purification procedure has been developed and the enzyme has been purified to homogeneity from two red seaweeds Gracilariopsis lemaneiformis and Gracilaria verrucosa. alpha-1,4-Glucan lyase was apparently a single polypeptide as a molecular weight of 111,000 was observed in SDS-gel electrophoresis, and 98,000 by gel filtration chromatography on Sephacryl S-200. Amino acid composition analysis of the enzyme showed high amounts of Asp/Asn, Gly and Glu/Gln. The isoelectric point of the enzyme was 3.9, as revealed by isoelectrofocusing. The concentrations of maltotriose, maltose and amylopectin that yield half of the maximum activity were 798 micrograms ml-1 (1.58 mM), 1,418 micrograms ml-1 (4.14 mM) and 1,600 micrograms ml-1, respectively. alpha-1,4-Glucan lyase exhibited a wide pH optimum range from pH 2.5 to 7.0 for maltose and from pH 3.5 to 7.5 for amylopectin. The optimal temperature for activity of the algal lyase was 50 degrees C when maltose or amylopectin was used as a substrate under the assay conditions. The Arrhenius activation energies were 45.8 and 44.0 kJ mol-1 for maltose and amylopectin as substrate, respectively. Only one form of alpha-1,4-glucan lyase was found in cell-free extracts of the two red seaweeds. PMID- 8461324 TI - Characterization and biological activity of 8-substituted analogues of 2',5' oligoadenylates. AB - Analogues of the 2',5'-linked adenylate trimer 5'-monophosphates (p5'A2'p5'A2'p5'A) containing 8-hydroxyadenosine and 8-mercaptoadenosine in the first, second, and third nucleotide positions were tested for their ability to bind to and activate RNase L of mouse L cells. The ability of p5'ASH2'p5'ASH2'p5'ASH (pASH3) (1c) to bind 2-5A dependent endonuclease was markedly decreased. On the other hand, an analogue of the 2',5'-linked adenylate trimer monophosphate substituted by 8-hydroxyadenosine in the first, second, and third nucleotide positions bound almost as well as parent 2-5A [pppA(2'p5'A)2] (p3A3) (1d) to RNase L. The 8-substituted analogues of 2-5A were more resistant to the degradation by the (2',5') phosphodiesterase. Of particular interest is monophosphate, pASH3 (1c) which possessed higher anti-HIV activity than pA3 (1a) or pAOH3 (1b). PMID- 8461325 TI - The interaction of sodium nitroprusside with peripheral white blood cells in vitro: a rationale for cyanide release in vivo. AB - Isolated monocytes and polymorphonuclear leukocytes release the cyanide anion from the hypotensive agent, sodium nitroprusside. The proposed mechanism involves the production of hydrogen peroxide which oxidizes the substitution inert d6 iron(II) transition metal complex to a labile d5 iron(III) complex. Consequently, the release of cyanide becomes more favoured. This mechanism is supported by the chemical release of the cyanide anion from sodium nitroprusside in vitro by hydrogen peroxide and the demonstrated ability of monocytes and polymorphonuclear leukocytes to generate hydrogen peroxide ex vivo when chemically stimulated by the nitroprusside anion. The results suggest that within a clinical environment white cell counts and cell activation induced as a consequence of disease processes may be important for predicting the toxicity of sodium nitroprusside. PMID- 8461326 TI - Calculating three-dimensional molecular structure of paliurine B from atom-atom distance and restrained energy minimization. AB - The conformation of paliurine B, a 13-membered cyclopeptide alkaloid isolated from Paliurus ramosissimus, has been determined from 2D NMR and distance geometry, followed by the restrained energy minimization calculation. The conformation of the 13-membered ring is well-defined but that of the acyclic dipeptide tail region is relatively disordered. In addition, the cavity in the 13 membered ring is just large enough to insert a magnesium ion but is a little small for calcium or sodium ions. PMID- 8461327 TI - Structure determination of glycosphingolipids of cultured human keratinocytes. AB - From cultured human keratinocytes, seven glycolipid fractions were isolated by DEAE and silica-gel column chromatographies, and further by HPLC on a silica-gel column. By means of 1H-NMR spectroscopy, fast atom bombardment mass spectrometry and GLC-mass spectrometry, one fraction was determined to contain acylglucosylceramides, which consist of amide linked omega-hydroxy fatty acids (C30:0, C30:1, C32:1 and C34:1), fatty acids linked to the omega-hydroxy fatty acids through ester linkages (C14:1, C16:1, C18:1 and C18:2), a long-chain base (d18-sphingenine), and beta-glucose. Five of the other fractions contained glucosylceramides, and the seventh fraction contained a mixture of glucosylceramides and galactosylceramides. Glucosylceramides containing long chain omega-hydroxy fatty acids, which are assumed to be immediate precursors of the acylglucosylceramides, were hardly detected in these glycolipid fractions. Six glucosylceramide fractions were separated due to differences in their fatty acids and sphingosines. On comparison with the results reported in our previous paper, the acylglucosylceramide content of the cultured human keratinocytes was about half that of human epidermis. Under the culture conditions used, the human keratinocytes did not differentiate into granular or horny cells. Taken together, the results suggest that the synthesis of acylglucosylceramides is not activated much in the cultured keratinocytes, but would be more activated in differentiated cells. PMID- 8461328 TI - Phosphatidylethanolamine derived from phosphatidylserine is deacylated and reacylated in rat hepatocytes. AB - The metabolism of phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC), derived from [3H]serine, has been studied in rat hepatocytes. After an initial pulse with radioactivity for 10 min and a chase for up to 240 min, cells were harvested and PS, PE and PC isolated. At the end of the pulse, greater than 90% of [3H]serine derived phospholipid radioactivity was associated with PS. In the subsequent chase, newly-made PS was degraded rapidly with less than 25% of the label lost from PS appearing in the PE and PC pools. In contrast, [3H]serine-labeled PE turnover was not detectable. Very little newly made PS was converted to PC. PE and PC were further fractionated into molecular species by high-performance liquid chromatography. We report that [3H]serine labeled PE is deacylated/reacylated with the major product of remodeling being 18:0-20:4 PE. In contrast, [3H]serine-labeled PC is not significantly remodeled. PMID- 8461329 TI - Lipoprotein and apoprotein profile of Japanese quail. AB - The present study delineated the lipoprotein and apoprotein distribution in Japanese quail. Quail lipoprotein was composed of three fractions: VLDL, d < 1.020; LDL, 1.020 < d < 1.081; HDL, 1.081 < d < 1.210. When animals were fed the cholesterol-free diet, HDL was the predominant form, LDL intermediate, VLDL and chylomicron were smallest in amount. Feeding of cholesterol induced a marked change in the lipoprotein profile: VLDL or chylomicron predominated over HDL and LDL. An apoprotein of 26 kD (molecular weight) was the major protein moiety comprising more than 50% of total apoprotein in the entire density range of lipoprotein class. Amino acid composition of 26 kD protein was similar to hen, rat and human apo A-I. N-Terminal 36 amino acid sequence of 26 kD protein showed 92% homology to chicken apo A-I and 11% homology to human apo A-1. The 26 kD protein did not react with the antibody raised against human apo A-I. These observation showed that the 26 kD protein was partially identical to apo A-I. PMID- 8461330 TI - Regulation of hepatic and non-hepatic apolipoprotein A-I and E gene expression during liver regeneration. AB - In this study, we have determined what tissues other than liver express apolipoprotein (apo) A-I and apo E genes during liver regeneration at the level of the specific mRNAs, and have compared these findings with the serum values of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low density lipoprotein (VLDL). Our results show that liver and intestine express most of the apo A-I mRNA during liver regeneration. Although apo E mRNA is expressed principally by the liver, its expression is reduced in liver during regeneration but is increased markedly in non-hepatic tissues, such as in intestine, kidney, lung and brain. These results suggest that humoral or circulating factors released during liver regeneration influence apolipoprotein E gene expression, not only in hepatic but also in non-hepatic tissue. PMID- 8461331 TI - Kinetic analysis and substrate specificity of a lysophospholipase from the macrophage-like cell line P388D1. AB - The kinetics of the lysophospholipase purified from the P388D1 macrophage-like cell line (Zhang and Dennis (1988) J. Biol Chem. 263, 9965-9972) have been explored. Three different lysophospholipids were used in these studies: 1 hexadecanoyllysophosphatidylcholine, 1-tetradecanoyllysophosphatidylcholine, and 1-hexadecanoyllysophosphatidylglycerol. Since all of the substrate dependence data for these substrates fit a Hill model, the enzyme's activity appears to be cooperative requiring at least two lipid molecules for full enzymatic activity. The enzyme did not show a preference for any of these substrates since their kcat ranged from 1.2 to 1.5 mumol min-1 mg-1 and their half-maximal activities ([S]0.5) were achieved at substrate concentrations between 15 and 33 microM. Enzymatic activity also appeared to be independent of the aggregation state of the substrate. No dramatic changes in rate could be associated with substrate aggregation at the critical micelle concentration. This is in marked contrast to some phospholipases A2 that exhibit dramatic activations when their substrates aggregate. In very dilute solutions, less than 0.5 micrograms/ml protein, the lysophospholipase loses activity irreversibly within minutes. This effect of low protein concentrations can be overcome by maintaining the enzyme in the presence of greater than 10 microM lysophospholipid. This inactivation can affect kinetic studies, since the [S]0.5s for this enzyme are usually in this range. We have found that increasing the protein concentration with a 'non-specific protein', e.g., cytochrome c, can protect the enzyme without affecting activity and, thus, allow valid kinetic data to be obtained over the full substrate concentration range. PMID- 8461332 TI - The effect of surface charge on the hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine and egg phosphatidylglycerol in aqueous liposome dispersions. AB - The hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine (PHEPC) and egg phosphatidylglycerol (EPG) were investigated as a function of surface pH at 60 degrees C. The bulk pH of the liposome dispersions was varied from pH 3.0 to 8.0. Charge was introduced to the liposomal bilayers by addition of EPG. Different electrostatic profiles were obtained at the bilayer-water interface by varying the surface charge density and the ionic strength of the buffer solutions. With the Gouy-Chapman equation the surface potential and with the Boltzmann equation the resulting shift in the surface pH compared to the bulk pH was estimated. The hydrolysis rate of both phospholipids increased with surface charge density in acidic medium; in alkaline medium the opposite was true. The hydrolysis rate constants, however, plotted as a function of surface pH agreed reasonably well with the results found with neutral liposomes. PMID- 8461333 TI - A phospholipase A2 inhibitor decreases generation of thiobarbituric acid reactive substance during lung ischemia-reperfusion. AB - A novel active-site directed specific inhibitor of phospholipase A2 (PLA2), 1 hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33), administered endotracheally co-dispersed in liposomes, significantly reduced the formation of thiobarbituric acid reactive substances (TBARS) in isolated rat lungs subjected to ischemia-reperfusion. Elevated conjugated dienes were unaffected. This contrasts with the effects of the cyclo-/lipoxygenase inhibitor 5,8,11,14 eicosatetraynoic acid (ETYA), which decreased formation of both TBARS and conjugated dienes (CD). The effects of MJ33 plus ETYA were additive for TBARS but results for CD were similar to ETYA alone. A similar dissociation of inhibition of TBARS and CD formation by MJ33 was observed with t-butyl hydroperoxide induced lipid peroxidation of isolated lung microsomes. Assay of lung homogenate with phosphatidylcholine as substrate showed that MJ33 selectively inhibited the Ca(2+)-independent acidic PLA2. MJ33 had no effect on thromboxane B2 release by the isolated lung, indicating the effects of acidic PLA2 inhibition do not involve the arachidonate cascade. MJ33 also partially prevented lung edema and lactate dehydrogenase release associated with ischemia-reperfusion. The observations show that this PLA2 inhibitor can be delivered to oxidant-sensitive lung sites by its co-dispersal in liposomes, and that oxidant-induced lipid peroxidation in this model of lung injury occurs in a complex lipid prior to PLA2 activity. PMID- 8461334 TI - Different effects of the hypolipidemic drugs pravastatin and lovastatin on the cholesterol biosynthesis of the human ocular lens in organ culture and on the cholesterol content of the rat lens in vivo. AB - This study aimed to investigate the influence of the hypocholesterolemic drugs pravastatin and lovastatin on the cholesterol biosynthesis in the ocular lens. Two model systems were used: a human lens organ culture system and an in vivo rat lens system. For measurements of cholesterol and fatty acid synthesis rates, human lenses were incubated for 20 h in the presence of [14C]acetate. Pravastatin and lovastatin were added 1 h prior to the addition of the radioactive label. In order to avoid the influence of differences relating to individual donors, one lens from each donor was incubated without drug (control) and the other lens was incubated in the presence of the drug. Statistical analysis showed that the fatty acid synthesis rate was not influenced by the drug. For each lens pair the percentage inhibition of the cholesterol synthesis caused by the drug was calculated. Using various concentrations of the drugs, a dose-response curve was composed for the inhibition of the cholesterol synthesis. The experiments showed that in the human lens organ culture system, lovastatin was 100-fold more potent than pravastatin in inhibiting the cholesterol biosynthesis. To study the in vivo influence of vastatins on the cholesterol content of the developing lens, Wistar rats were weaned at day 21 of age and subsequently the pups were fed a control diet or drug-containing diet (10, 50 or 100 mg lovastatin/kg chow) for a 3-week period. At the end of diet intervention, doses of 50 or 100 mg lovastatin/kg chow had caused a reduction of about 20% of the lenticular cholesterol content compared with controls. No effect on the lens cholesterol content by pravastatin was observed. Both human ex vivo and rat in vivo experiments show that lovastatin much more strongly inhibits the lenticular cholesterol synthesis than does pravastatin. PMID- 8461335 TI - Different hydrolytic efficiencies of adipose tissue lipoprotein lipase on very low-density lipoprotein subfractions separated by heparin-Sepharose chromatography. AB - Human very-low-density lipoproteins (VLDL) were subfractionated by heparin Sepharose chromatography into an unbound (A) and three bound (B, C and D) populations at increasing ionic strengths. Subfractions were characterized regarding their chemical composition and efficiency of triacylglycerol hydrolysis by rat adipose tissue LPL. The triacylglycerol content decreased, whereas the cholesterol and protein contents increased from subfractions A and B to subfraction D. VLDL-D showed the highest apo E/apo C ratio, though all the subfractions contained appreciable apo E. Appearance of VLDL-A resulted from exceeding the binding capacity of the column, since practically all its particles eluted at positions of bound VLDL under re-chromatography. Subfractions B, C and D stimulated LPL activity on emulsified tri[14C]oleoylglycerol to a similar extent, indicating that their apo C-II content was equally effective activating LPL. Incubation of tri[14C]oleoylglycerol labeled VLDL subfractions with fat pad pieces in the presence or absence of heparin resulted in greater hydrolysis and fatty acid uptake for VLDL-B and -C than for VLDL-D, a pattern observed over a wide range of LPL activities in the media. We conclude: (1) any VLDL particle can interact with heparin, which is consistent with the presence of apo E in all the subfractions, and (2) triacylglycerols in apo E-rich VLDL are less efficiently hydrolyzed by LPL than those in apo E-poor particles. We propose that richness in apo E impairs LPL action upon VLDL and decreases the rate of delivery of fatty acids to peripheral tissues. PMID- 8461336 TI - The effects of probucol on the levels, structure, composition and metabolism of plasma lipoprotein in rats. AB - The effects of probucol administration on the levels, structure, composition and metabolism of plasma lipoproteins were determined in male rats. Probucol caused a 25% decrease of plasma cholesterol and a 20% decrease of plasma triacylglycerols. The effect was more pronounced on lipoproteins of density less than 1.063 g/ml ( 35%) than on density greater than 1.063 g/ml (-21%). The density of LDL, HDL-1 and HDL-2 separated by ultracentrifugation on a zonal rotor was shifted towards a higher density. The content of cholesteryl esters increased in VLDL and LDL and decreased in HDL-1 and HDL-2. LDL, HDL-1 and HDL-2 were relatively enriched with proteins. The intravascular metabolism of 125I-labeled apo A-I was identical in control and probucol-treated rats with a circulating half-lifetime of 9.5 h. The circulating half-lifetime of LDL labeled biosynthetically with [3H]cholesteryl esters was also identical, 6.5 h. The circulating half-lifetime of [3H]cholesteryl esters in HDL-2, in contrast, was 9.5 h in control rats and 7.5 h in probucol-treated animals. Plasma cholesterol ester transfer activity was almost undetectable in either control or probucol treated animals. The investigation demonstrates a pronounced effect of probucol on plasma lipid and lipoprotein levels in rats, on cholesterol ester distribution between lipoproteins and on lipoprotein transport rates in the plasma. These effects may contribute to the anti-atherogenetic action of probucol. PMID- 8461337 TI - Signal-transduction mechanisms of ATP-stimulated phosphatidylcholine secretion in rat type II pneumocytes: interactions between ATP and other surfactant secretagogues. AB - ATP stimulates phosphatidylcholine secretion in type II cells, an effect that is mediated by both adenosine A2 receptors coupled to adenylate cyclase and P2 receptors coupled to phosphoinositide-specific phospholipase C. Activation of these effector enzymes leads to formation of cAMP, diacylglycerols and inositol trisphosphate (IP3). cAMP in turn activates cAMP-dependent protein kinase, diacylglycerols activate protein kinase C and IP3 promotes Ca2+ mobilization. To further investigate the signal-transduction mechanisms mediating the ATP effect, we examined its action in combination with that of other surfactant secretagogues: 5'(N-ethylcarboxyamido)adenosine (NECA), a A2 agonist that activates adenylate cyclase; TPA (12-O-tetradecanoylphorbol-13-acetate), a direct activator of protein kinase C; and ionomycin, an ionophore that increases intracellular Ca2+. The effects of NECA, TPA and ionomycin were additive and thus consistent with independent signaling mechanisms. However, the effects of all combinations of three or four secretagogues that contained ATP were 10-20% less than additive. This suggested that ATP and other secretagogues act via common mechanisms. Calmodulin antagonists decreased the effects of ionomycin and ATP by approx. 60% and 30%, respectively, but did not decrease the effects of NECA, terbutaline or TPA. Complete inhibition of the effect of ATP was achieved with a combination of a calmodulin antagonist, an A2 antagonist and a protein kinase C inhibitor. These and previous data suggest that the stimulatory effect of ATP on phosphatidylcholine secretion in type II cells is mediated by three signal transduction mechanisms: activation of cAMP-dependent protein kinase; activation of protein kinase C; and a calmodulin-dependent mechanism. PMID- 8461338 TI - The effect of the HMG-CoA reductase inhibitor simvastatin and of cholestyramine on hepatic apolipoprotein mRNA levels in the rat. AB - We have administered the hypolipaemic drugs simvastatin and cholestyramine to rats, both separately and together, to determine whether drug-induced changes in plasma apo lipoprotein levels occur through regulation of hepatic genes coding for apolipoproteins (apos) AI, AIV, E and B. Cholestyramine alone had little effect on either the plasma levels of the apolipoproteins studied or their hepatic mRNA levels. However, simvastatin, either alone or in combination with cholestyramine, produced marked changes in both of these parameters. While simvastatin plus cholestyramine lowered mRNAs for apo AIV, apo E and apo B by 50%, 37%, and 55%, respectively, the treatment resulted in an increase of 150% in apo AI mRNA. This combined drug treatment caused a lowering in plasma concentration of all four apolipoproteins which failed to reach significance with apo E. Relative to controls, the values decreased to 83 +/- 14% for apo AI, 67 +/ 8% for apo AIV and 73 +/- 15 for apo B. An important novel finding of the present study, was that hypolipaemic drugs caused the apo B mRNA levels in rat liver to decrease. Previous reports have shown that although dietary fat or hormones caused marked changes in the concentration of circulating lipoproteins, they failed to alter apo B mRNA content. We suggest that the synthesis of apo B is subject to both pre- and post-translational regulation. PMID- 8461339 TI - Integration of mass spectrometry into strategies for peptide synthesis. PMID- 8461340 TI - Charge-remote fragmentation in a disulfide-containing peptide, [Pen]-enkephalin, under fast atom bombardment collisionally activated dissociation conditions. AB - Fast atom bombardment collisionally activated dissociation tandem mass spectrometry (FAB CAD MS/MS) of a disulfide-containing peptide, [2-D penicillamine, 5-D-penicillamine]- enkephalin ([Pen]-enkephalin), is described. Unlike those of most other disulfide-containing peptides investigated, CAD of the native, unreduced protonated molecule of [Pen]-enkephalin yields a relatively large number of fragment ions. Most of the peaks in the CAD spectrum represent fragmentations of the peptide backbone with 'unsymmetric' cleavage of the disulfide bond with charge retention on the N-terminus; the fragment ions generally do not contain a sulfur atom or a disulfide group. The CAD spectrum of the N-terminal ethyl-triphenylphosphonium derivative, on the other hand, shows few fragment ions and is dominated by the single peak at m/z 523. This dominant ion also results from 'unsymmetric' cleavage and corresponds to the analogous protonated species (m/z 235) in the spectrum of the underivatized peptide. The chemical method of charge localization by triphenylphosphonium derivative formation at one end of the peptide is shown to be useful for investigating fragmentation mechanisms in FAB CAD MS/MS. Comparison of the CAD spectra of derivatized and underivatized [Pen]-enkephalin suggests that charge-remote fragmentation plays a significant role in the high-energy dissociation of this disulfide-bonded peptide. PMID- 8461341 TI - Direct observation of a DNA quadruplex by electrospray ionization mass spectrometry. AB - In 10 mM sodium phosphate, pH 7.6, containing 0.1 mM ethylenediaminetetraacetic acid, ions correspondings to the non-calent, four-stranded oligonucleotide, d(CGCG4GCG)4, were detected by negative ion electrospray ionization (ESI) mass spectrometry at a low nozzle-skimmer (delta NS) bias (-150 V), but not at a higher delta NS bias (> -250 V). In contrast, when the sample was desalted and analyzed by ESI mass spectrometry at a low delta NS bias only ions for the single stranded d(CGCG4GCG) species were observed. These data agree with spectroscopic evidence which showed that oligonucleotides with the sequence motif 5'd(CGCGnGCG)3', where n = 2-5, formed stable four-stranded complexes in the presence of monatomic cations, like K+, Ca2+, Na+ and Li+, but not in their absence. PMID- 8461342 TI - Particle beam liquid chromatography/mass spectrometry with negative ion chemical ionization for the confirmation of ivermectin residue in bovine milk and liver. AB - Particle beam liquid chromatography/mass spectrometry (LC/MS) using negative ion chemical ionization was applied to the analysis of ivermectin residue in bovine milk and liver. Samples were prepared by liquid/liquid extraction followed by alumina B solid-phase extraction clean-up. On-line LC/MS of extracts was carried out on a C-18 bonded silica column. Signals were observed from on-column injections of 4 ng dihydro-avermectin B1a (H2B1a) in extracts equivalent to 2 ml milk or 0.3 g liver. The specificity required for a regulatory confirmation procedure was achieved by monitoring the H2B1a molecular ion and four fragment ions. Ion chromatogram peak areas were at least three times greater than control samples integrated over the same time window. Coeluting matrix compounds enhanced the response and altered the abundance pattern of H2B1a. To compensate for this matrix effect, control milk extracts were spiked with H2B1a standard and used for the abundance matching for the abundance matching requirement of regulatory confirmation. PMID- 8461343 TI - The role of vertebral and internal carotid artery disease in the pathogenesis of vertebrobasilar transient ischemic attacks. AB - Color-coded duplex sonography has improved the evaluation of the hemodynamics of the vertebral arteries (VA). A reliable differentiation between a normal vessel, hypoplasia, stenosis and occlusion of VA can now be made. We studied two groups of patients in a prospective study with isolated carotid artery disease (n = 48), and with a combination of carotid and vertebral artery disease (n = 14), to determine the role of VA in the pathogenesis of transient ischemic attacks (TIAs) in the vertebrobasilar system. Apart from the existing arteriosclerotic changes of the internal carotid arteries, the condition of the VA was of importance for the occurrence of TIAs in the vertebrobasilar territory. We found that 8% of the patients with isolated hemodynamically relevant stenosis or occlusion of one or both internal carotid arteries had a TIA in the vertebrobasilar territory. Patients with combined carotid and vertebral artery disease had an increase of TIAs in the same region in 71%. The high rate of TIAs in this group might be attributed to the combined effect of carotid and vertebral artery disease, as a third group (n = 30) with isolated vertebral artery disease showed TIAs in only 13%. PMID- 8461344 TI - Long-term stability of subtypes in schizophrenic disorders: a comparison of four diagnostic systems. AB - The long-term stability of subtypes of schizophrenic disorders in 148 narrowly defined schizophrenic patients according to four diagnostic systems was compared. The patients were investigated longitudinally for 23 years on average (range 10 50 years). Patients who experienced only one episode and those who were permanently hospitalised were excluded on methodological grounds. Of the remaining 100 patients, a total of 461 episodes were classified into various subtypes according to the criteria of DSM-III-R, ICD-10, the positive/negative dichotomy, and Schneider's first-rank symptoms. It was found that long-term stability of subtype in schizophrenic disorder was not the rule but the exception. The frequency of stable course was found to be depend on the type of the initial episode. In most cases a subtype change occurred within the first few years of the illness with no clear direction. In later stages of the illness the relative frequency of episodes predominated by negative symptomatology increased. The findings were similar for DSM-III-R, ICD-10 and positive/negative dichotomy. Only in patients beginning without first-rank symptoms were more stable than non stable courses found. The results of this study do not support the assumption that stable subtypes are nosological or etiopathogenetic subentities of schizophrenic disorders. PMID- 8461345 TI - Estimation of the dimensionality of sleep-EEG data in schizophrenics. AB - Deterministic chaos could be regarded as a healthy flexibility of the human brain necessary for correct neuronal operations. Several investigations have demonstrated that in healthy subjects the dimensionality of REM sleep is much higher than that of slow wave sleep (SWS). We investigated the sleep-EEG of schizophrenic patients with methods from nonlinear system theory in order to estimate the dynamic properties of CNS. We hypothesized that schizophrenics would reveal alterations of their dynamic EEG features indicating impaired information processing. In 11 schizophrenic patients, the EEG's dimensionality during sleep stages II and REM was reduced. We suggest that such lower dimensional chaotic processes might be associated with an overloading of neuronal networks during sleep and therefore the psychopathology of schizophrenics might be due to impaired complexity of their EEG's dynamics. PMID- 8461346 TI - Incidence of cycloid psychosis. A clinical study of first-admission psychotic patients. AB - The concept of cycloid psychosis has gained increasing acceptance during recent decades. Using the diagnostic criteria of Perris and Brockington, an intelligible delineation of a group of patients has been obtained. Few epidemiological data on cycloid psychosis have been reported so far. The objective of the present study was to describe the one-year incidence of cycloid psychosis in a clinical sample. The diagnostic registers of all patients hospitalized for a functional or an organic psychosis and discharged in the year 1983, in Lund, Sweden were investigated. 514 patients were identified of whom 83 were admitted to hospital for the first time. 29 of these patients had a functional psychosis and were below the age of 50. In this age group 7 cases (4 women, 3 men) fulfilled the diagnostic criteria of cycloid psychosis and thus constituted almost one fourth of all first admissions of functional psychoses that year. The one-year incidence for first admission in cycloid psychosis was 5.0 per 100,000 inhabitants in women and 3.6 per 100,000 inhabitants in men within the age group 15-50 years in the catchment area of 163,175 persons. We conclude that cycloid psychosis constitutes a considerable proportion of functional psychoses in both sexes. PMID- 8461347 TI - An empirical comparison of diagnoses and reliabilities in ICD-10 and DSM-III-R. AB - The psychiatric classification systems ICD-10 and DSM-III-R were compared by applying both sets of diagnostic criteria to the same sample of patients suffering from affective and psychotic disorders. Four independent raters assessed diagnoses according to both systems to 100 written case records which had been prepared in a traditional, standard format. The International Diagnostic Checklists (IDCL) were employed to rate relevant psychopathological signs and symptoms and to apply diagnostic decision rules. The results showed that ICD-10 yielded a generally higher reliability for all main disorders except for bipolar disorder. Overall reliability was kappa = 0.53 for diagnoses according to DSM-III R and 0.59 for diagnoses according to ICD-10. Agreement was best for affective disorders, moderate for schizophrenia and inacceptable for schizoaffective disorder. Insufficient boundaries were found in both systems between schizoaffective disorder on one side and schizophrenia and bipolar disorder on the other side. The different duration criteria for schizophrenia of six months in DSM-III-R and one month in ICD-10 tend to have considerable consequences for frequency rates of schizophrenia in a typical clinical setting. PMID- 8461348 TI - Routine psychiatric examinations guided by ICD-10 diagnostic checklists (International Diagnostic Checklists). AB - A systematic assessment of psychiatric diagnoses according to the new classification system ICD-10 can be guided and enhanced by the International Diagnostic Checklists (IDCL). This instrument was developed and evaluated primarily for use in routine clinical care. It consists of 30 separate lists in pocket form, each assigned to a specific disorder and allowing immediate and operationalized diagnostic decisions (without the need of computer assistance). Personality disorders are covered by a separate 12-page booklet (IDCL-P). Examples of the checklists are given together with possible areas of application. First studies have indicated good clinical practicability and satisfactory to excellent diagnostic reliability. PMID- 8461349 TI - Partners in adversity: I. Study design and context. AB - This paper presents results from a longitudinal study of three groups of married women undertaken in Edinburgh. Each study group was identified through their common experience of a particular stressful situation. Recruitment to the two principal study groups required that a marital partner had either recently died or had recently experienced a myocardial infarction (MI). The third group consisted of those women recently entering a Women's Aid refuge. Interviews were completed with 64 bereaved women, 143 women shortly following their partner's MI and 32 women entering a refuge. Where possible, follow-up interviews were undertaken about three months following the first interview. Detailed assessments were made of the 'target' stressful experiences, of any others that had occurred, and of the course and nature of the respondent's mental health during the study period. Additional assessments included measures of style of coping and of the support resources available and utilized. This report presents details of the design and methodology of the study and of the respondents' experiences of the specific stressors that recruited them to the study. It also provides the background to an examination and analysis of the sequencing of adverse experiences reported in the companion paper. PMID- 8461350 TI - Partners in adversity: II. Measurement and description of stressful event sequences ('complexes'). AB - Three groups of married women were studied with each defined by their experience of a different stressful incident (the target event). In the first (the Coronary Group), the husband had suffered a non-fatal myocardial infarction whilst in the second (the Bereaved Group), he had recently died. In the third (the Refuge Group) the subject had just entered a refuge run by Women's Aid in order to flee from her husband. This paper concentrates on the description and measurement of the sequence of these experiences and of others occurring within the same study time. The Bedford College core rating scheme together with other ratings were applied. In the Coronary group, the target event was rated as a severe threat in 46.9% of cases, and also rated as being of uncertain outcome and hopeless. Over one quarter of the sample received other ratings such as subject-focused and choice of action. Virtually all the bereavements were rated severe threat, loss, hopeless and subject-focused. The refuge target events were mostly rated of only moderate threat but differed widely on other characteristics. In the 6 months prior to the target event, other severe events tended to occur most frequently to the Refuge group and least frequently to the Coronary group. However, these other severe events were mostly connected with the target event and what had lead up to it. Issues concerning the measurement of the principal study events and the other stressors experienced are discussed. PMID- 8461351 TI - Is schizophrenia really on the decrease? AB - Directly age standardized rates of first admission schizophrenia in Denmark (1991: 5.1 million inhabitants) decreased significantly with a slope of -0.16 and -0.13/100,000 inhabitants fifteen years and above for males and females respectively from 1971 to 1991 when examined by help of the Danish nation-wide psychiatric case register in the Institute of Psychiatric Demography, Aarhus. A control for changes in diagnostic delay/changing diagnostic patterns does not affect the findings. Various nosological factors might cause the decrease, e.g. changing structure in organization of treatment facilities, decreasing number of beds (50% in Denmark during the period investigated) and correlated with this: increasing suicide rates among pretreatment schizophrenics, increasing rates of schizophrenics not yet diagnosed in shelters for homeless and in institutions for criminals. The decrease might be genuine. In connection with this the theories about damage to the fetus during the gestation period are briefly discussed. PMID- 8461352 TI - The effect of war on suicide rates. A study of France from 1826 to 1913. AB - An analysis of suicide rates in France from 1826 to 1913 indicated that suicide rates were lower during years of war than during years of peace. This effect was stronger for female suicide rates than for male suicide rates and seemed to hold both for major and minor wars. PMID- 8461354 TI - Special issue: The family and HIV disease. PMID- 8461353 TI - A test-retest study of cerebral blood flow during somatosensory stimulation in depressed patients with schizophrenia and major depression. AB - Six depressed patients with schizophrenia and 6 depressed patients with major depression were investigated before and during somatosensory stimulation (SS) with Tc-99m HMPAO SPECT. 8 controls were investigated only under resting conditions. The results can be summarized as follows: 1. Both psychiatric patient groups were hypofrontal (dorsolateral prefrontal cortex) compared to controls. 2. Hypofrontality was further enhanced by SS, significantly only in affective psychoses in the right inferior frontal lobe and in the right frontal hemisphere in total, in schizophrenia in the left dorsolateral prefrontal cortex. 3. Within the frontal lobes different regions were affected by SS in the two diagnostic groups. 4. In the right inferior parietal lobe SS response was significantly different in the two illnesses with schizophrenia showing a relative decrease, affective psychoses showing a relative increase of activity. 5. SS produced an increase of cerebral blood flow in subcortical regions (statistically significant contralateral to SS in thalamus and basal ganglia, ipsilateral to SS in cerebellum), a pattern which was common to all psychiatric patients. 6. Somatosensory cortex flow was not changed by SS. In conclusion, we could not fully confirm our hypotheses that similar blood flow abnormalities in different illnesses during SS are only caused by similarities in depressive psychopathology. Instead, depressed patients with schizophrenia were different from depressed patients with major depression in showing decreased activity in interrelating brain regions participating in an attentional network. PMID- 8461355 TI - The extended family and support for people with AIDS in a rural population in south west Uganda: a safety net with holes? AB - It is commonly assumed that the extended family in Africa provides a safety net for individuals in times of need. This paper examines this assumption using data on the care of people with AIDS in a rural population in South West Uganda. Over a six month period data were collected by counsellors on the care given to 30 (17 women, 13 men) AIDS patients by their families. In 27 of the 30 cases there was evidence of limited care. Various reasons were given for this by the carers, including lack of food and money for medications and the carer's other family responsibilities. For 17 clients who died during the study period, records of seven cases show that other relatives were asked to help with care but refused on the grounds of poverty or other commitments. However, in all but one of these cases extended families did provide assistance for the funeral. The findings suggest that there is a need to question the assumption that the extended family, in the culture under study, is able to provide adequate support for AIDS patients. PMID- 8461356 TI - World Health Organization Global AIDS Statistics. PMID- 8461357 TI - Significant relationships and social supports of injecting drug users and their implications for HIV/AIDS services. AB - Strong social support networks have been associated with positive outcomes for health and well-being throughout the life-cycle. This paper investigates the structural and functional nature of social support networks of 100 injecting drug users (IDUs) in Sydney and the implications for HIV/AIDS services. Using a modified ISEL respondents saw support in terms of its tangibility of people and support, in terms of an appraisal of having friends, and as a self-esteem measure. We found the majority of respondents 'hung around' with other IDUs, lived with other IDUs, and were satisfied with the support they received from their friends. Friends appeared to be a more important source of social support than biological families and if respondents were to become HIV infected they would be more open about their status with friends than family. Where family was involved in support it was likely to be provided by mothers and siblings who were also the family members who knew about the respondent's drug use. There was no relationship between numbers of supports and satisfaction of support, suggesting quality and quantity of support were independent. Non-social supports were conceptualized primarily in terms of medical services. PMID- 8461358 TI - The family and HIV disease. PMID- 8461359 TI - The child in the family--responding to AIDS and HIV. AB - This study examines the psychosocial needs of children with AIDS and HIV infection based on a cohort of 18 infected children. Fifteen of the children live with their mothers, nine of whom are single mothers. For 14 children the mother is HIV +ve and for a further 8 the father is also HIV +ve. Many children have siblings (10), but only one of these is infected. Close family and grandparents are rarely involved in care and only one child, the oldest, is aware of parental and personal HIV status. Where children attend school or preschool centres none have been informed of the child's HIV infection. Cultural issues are prevalent, especially marked when English is not the first language (n = 10) which renders obstacles for counselling and developmental appraisal. Children in this group are hospitalized more frequently than the parents. Child and parental hospitalization is problematic. Three case situations arising in this group are described in some detail to highlight the nature of the emotional challenges facing carers and service providers. PMID- 8461360 TI - Psychological distress and the role of significant others in a population of gay/bisexual men in the era of HIV. AB - This study, based on The Conservation of Resources Theory (COR), explores the relationship between social resources and psychological distress, as reported by gay/bisexual men who are at varying degrees of risk for HIV. This study involves theory-based stress research, and adds to the body of literature that addresses social support and gay men. Specific emphasis was placed on the process of social support by significant others in relationship to the devastating impact HIV has on the gay/bisexual community. The investigators employed an ex-post facto design that was guided by past and present theoretical and empirical data, and by specific research hypotheses. The findings suggest that facets of social support appear to be interactively related to the perceived threat of HIV in predicting distress. In general, this study supports COR theory in that resources were related to the experience of psychological distress, yet it emphasizes that the relationship between support and gay men is complex, and thus generalizations from findings based on research with the majority culture may not apply to a population of gay/bisexual men. Implications for future research are also provided. PMID- 8461361 TI - The impact of HIV/AIDS on the family and other significant relationships: the African clan revisited. AB - Although changing in size, structure and function, the African family has persistently maintained its place as the central human social unit. Beyond the traditional African family--whether in the nuclear or the extended form--is a network of people, most of whom are connected by kin or blood relationships, termed the clanship system. Patterns of family treatment and care are deeply embedded in this wider kinship system. The AIDS epidemic has caused adverse psychosocial and economic consequences leading to change in the family structure, and thus disturbed the capacity of the nuclear and extended family to respond to the needs of members afflicted by HIV and AIDS. Hence, the clanship system could become the locus of AIDS activity designed to ensure the well-being and continuity of the family where its leadership undertakes to sustain, to reorganize, or to create wholly new families or structures among populations being devastated by AIDS. New associations based on common emotional bonds of caring beyond kinship ties will be necessary to support some vulnerable members. However, for such to prove durable in the troubled socio-economic context of Sub Saharan Africa, these will need strong links to or derive their legitimacy from the resilient traditional social network, the African kinship system. PMID- 8461363 TI - AIDS and the family: implications for counselling. AB - The presence of HIV spectrum illness stimulates a powerful emotional reaction from a patient's family and friends. Grief and shock over the infection, and its implications are frequent observations. Sadness, anxiety, helplessness and anger are also common. Health care staff should address these responses in order to strengthen coping skills and maximize interpersonal comfort. Stigmatization and isolation are major stressors. Bereavement is complicated by fear, shame, dependency and hopelessness. Therefore, a task in counselling is to maintain the integrity and supportiveness of the patient's social unit by encouraging open communications between those involved and by educating about AIDS. Information should be provided on HIV transmission, self-protection, and illness progression as well as the safety of causal contacts and the practices of 'safer sex'. The significant others should retain outside interests and be encouraged to seek help for patients from supportive social agencies. Instillation of hope lends benefit to patient, family and friends. Kind, non-judgmental counselling and good quality medical care should be made available, especially since HIV-related disorders are increasingly becoming a chronic disease. Advocacy for the significant others translates into better adjustment and it enhances the patient's medical prognosis. PMID- 8461362 TI - AIDS and the urban family: its impact in Kampala, Uganda. AB - Twenty-two families with one or more adult members with AIDS were extensively interviewed about sociodemographic variables, knowledge of AIDS, responses to AIDS, material needs, psychological state and perception of stigma. A total of 24 individuals were enrolled. Seven subjects did not permit contact with family members. Of the 24 subjects, four denied that they have AIDS, four informed everyone in the household of the AIDS diagnosis, eight told no one at all, and eight told some of their family. Subjects reportedly did not tell their family because the family would worry, they feared rejection, it is none of their business or they wouldn't understand. Family members expressed fear of loss, shock and disbelief at the diagnosis, but did not reject the subject or fear infection. Persons with AIDS and their families expressed fear of rejection from those outside the household due to the perceived stigma associated with AIDS. The labelling of someone as having AIDS relates to their physical condition, so with declining health, subjects and their families may avoid outside contacts. A direct impact of AIDS is to diminish mobility, decreasing available economic resources. These data indicate the importance of assisting families responsible for caring for AIDS patients. PMID- 8461364 TI - A family with HIV and haemophilia. AB - An Indian Sikh family affected with both HIV and haemophilia is described. The use of interpreters; the regular follow-up in the Concorde trial; family therapy and help with practical problems have been approaches used to help the family despite language and cultural differences. PMID- 8461366 TI - [Another look at serum bactericidal activity]. PMID- 8461365 TI - Social support and HIV. AB - This paper reviews research about the relationship between social support and health for people with HIV. Current studies linking social support and HIV are described and the major findings summarized in order to identify gaps in the literature. It is argued that, to date, research in this area has focused primarily upon gay white men in the USA at a symptomatic stage of the illness. There are few studies which have considered the impact of social position on the relationship between social support and health, and few which have included HIV negative controls. Whilst there is evidence of a link between social support and the psychological well-being of people with HIV, research is still in its infancy. Much information is required about which particular aspects of social support and health are associated, how this association changes over time according to the stage of the disease, and with the socio-economic and cultural characteristics of those with HIV. PMID- 8461367 TI - [Utilization of an emergency service by patients with HIV infection]. AB - BACKGROUND AND METHODS: To know the impact of HIV infection in a hospital emergency department the health care episodes of seropositive individuals are reviewed in a retrospective study from the January 1 to March 31, 1992. Cases have been identified comparing the list of those infected by HIV with the users of the department during the period studied. RESULTS: 430 episodes in 288 patients (1.5 episodes/patient) have been included constituting 2.3% of the total. 76.4% were males, with a mean age of 29.2 years (range, 18-59) and 60.2% were evaluated the medical area. Hospital admission was indicated on 147 occasions (34.2% versus 19% of seronegatives; p < 0.001). The most frequent diagnoses were infections which were or were not associated to alteration of cellular immunity (32.8%) and complications related with the abuse of opioid substances (23.7%). CONCLUSIONS: The pathology associated to HIV infection and to the abuse of intravenous drugs constitutes a frequent problem in the emergency departments. The infectious diseases which are or are not associated to alteration in cellular immunity, complications related with the consumption of opioids and the high index of admissions are of note. Professionals carrying out health care work in this medium must be familiarized with the diagnosis and treatment of these processes. PMID- 8461368 TI - [Resistance in Haemophilus influenzae in Spain. 2d study (1990)]. AB - AIM: To study the resistance to strains of H. influenzae simultaneously isolated during 1990 in 10 Spanish cities with this being the second multicentric study carried out in Spain. METHODS: Three hundred eight strains of H. influenzae were consecutively isolated with less than 50% being from the respiratory tract. The sensitivity by microdilution in supplement Isosensitest was studied. RESULTS: Thirty-five percent of the strains were producers of beta-lactamase which predominate among those isolated in systemic infections and specially among those from Madrid (58.78%) and Barcelona (61.8%). The strains producing beta-lactamase were more resistant to all the antimicrobials than the non producers. Five point two percent of the strains were resistant to ampicillin by non enzymatic mechanisms. Resistance to chloramphenicol is frequent (28.6%) especially among strains producing beta-lactamase, strains of ocular origin and ORL (46%) and systemic infections (74.3%). The distribution is irregular, being more frequent in Seville (66.7%) and not detectable in Barcelona. Resistance to tetracycline is also usually linked to the production of beta-lactamase and not necessarily to that of chloramphenicol. Resistance to cotrimoxazole is the most frequent (67.5%) specially in Valladolid (87.5%). Resistance to cefaclor is of 60.7% being the most frequent among those isolated from ocular processes and ORL. Only 28 strains (9.1%) were sensitive to all the antimicrobials tested. Thirty-nine percent were multiresistant. CONCLUSIONS: The authors found a slight increase in the high resistance detected in 1986. This increase was not uniform in all of Spain being significant in Madrid with producers of beta-lactamase, in Seville to chloramphenicol, to tetracycline in Bilbao and cotrimoxazole in Valencia. PMID- 8461369 TI - [Prevalence of serotype 0:12 among strains of P. aeruginosa causing nosocomial infection in Spain (1980-1991)]. AB - BACKGROUND: The aim of the present study was to characterize P. aeruginosa strains causing nosocomial infection in Spain between 1980-1990 with special emphasis on the incidence of serotype 0:12 strains. METHODS: 11,411 strains of P. aeruginosa from hospital-acquired infections were studied and epidemiologically characterized by phage-typing, serotyping and sensitivity to antimicrobial agents. The strains of the 0:12 serotype were analyzed by isoenzyme analysis. RESULTS: Although the major serotypes throughout the period studied were: 0:1, 0:6 and 0:11, the existence of serotype 0:12 strains (6%) were detected which had produced nosocomial outbreaks in surrounding countries. This serotype is homogeneous in that the epidemiologic markers and patterns of sensitivity to antibiotics and the multienzyme analysis demonstrate uniformity in the electrophoretic patterns of all the strains studied. CONCLUSIONS: The 0:12 serotype is in Spain indistinguishable by phage typing and studies of antibiotic sensitivity. It may be considered as being of clonal origin and is probably equal to that existing elsewhere in Europe. PMID- 8461370 TI - [Follow-up of the quantitative serological response to the treatment of Helicobacter pylori infection in children]. AB - BACKGROUND: The aim of the present study was to know the usefulness of a enzyme immunoanalysis (EIA) technique for the monitorization of the serologic to treatment of infection by Helicobacter pylori in Spanish children. METHODS: 17 children with digestive symptomatology in whom the diagnosis of infection by Helicobacter pylori was confirmed and eradication was objectified following a month of treatment with amoxycillin, metronidazole and Bismuth subcitrate were studied. In each patient a biopsy of the gastric mucosa was performed and a sample of serum was withdrawn for initial diagnosis and for control of eradication once treatment had finished (mean time between diagnosis and confirmation of eradication was 79.6 +/- 33.5 days). The samples of gastric mucosa were processed by standard methodology (histologic and/or culture). Serologic determinations (IgG and IgA) were carried out using a EIA technique (Pyloriset EIA-G and EIA-A; Orion Diagnostica). RESULTS: In 12 of the 17 patients resolution of the clinical symptomatology was produced. A decrease in the levels of IgG was observed in 15 (88.2%) and of IgA in 14 (82.3%) of all the children studied. A significant difference was found between the mean values of the levels of IgG (p < 0.01) and IgA (p < 0.05) in the 17 patients at the time of diagnosis and following eradication. CONCLUSIONS: In agreement with the present results the series study of the quantitative level of antibodies IgG and IgA versus Helicobacter pylori is shown as an adequate instrument for evaluating the response to treatment in pediatric patients. PMID- 8461371 TI - [Oro-esophageal candidiasis resistant to fluconazole in patients with AIDS]. AB - BACKGROUND: Fluconazole-resistant Candida albicans has been seldom reported in the literature. in this study, two clinical cases of oro-esophageal candidosis resistant to this antifungal drug are described. METHOD: Infection was confirmed by isolation of yeasts (culture of mouth swabs, oesophagoscopy and histology of biopsy specimens). In vitro antifungal susceptibility tests were performed with standard methods (NCCLS). RESULTS: Clinical and microbiological fluconazole resistant Candida albicans was isolated. CONCLUSIONS: Causes of development of resistances are commented, and the role of immunodeficiency and the possibility of a Candida strain selection is discussed. PMID- 8461372 TI - [Acute toxoplasmosis. Laboratory diagnosis]. AB - BACKGROUND: The microbiological diagnosis of acute toxoplasmosis in immunosuppressed patients, cannot, usually, be done through serological techniques. The methods for isolation or direct detection of parasite are the only ones that might be helpful to determine an earlier diagnosis, on these patients. METHODS AND RESULTS: The use of urine in 3 patients with acute toxoplasmosis, allowed us to isolate the parasite after inoculation of the sample in human embryonic fibroblast cell line (MRC-5). CONCLUSION: In our opinion urine could be an adequate sample for isolation or detection of Toxoplasma gondii in immunosuppressed patients, and an alternative to serological methods, as well. PMID- 8461373 TI - [Problems in studying sensitivity in Haemophilus influenzae]. PMID- 8461374 TI - [Bacterial keratitis. Report of a case]. PMID- 8461375 TI - [Isolation of Leclercia adecarboxylata in a cirrhotic patient]. PMID- 8461376 TI - [Spontaneous splenic rupture secondary to Salmonella typhi infection]. PMID- 8461377 TI - [Evaluation of the cut-off point in the serological diagnosis of Helicobacter pylori infection in children using an enzyme immunoassay technique]. PMID- 8461378 TI - [Bacteremia caused by Campylobacter jejuni resistant to nalidixic acid and fluoroquinolones]. PMID- 8461379 TI - What about those monkeys that got T-cell lymphoma? PMID- 8461380 TI - Direct in vivo gene transfer to airway epithelium employing adenovirus-polylysine DNA complexes. AB - Adenovirus-polylysine-DNA complexes were evaluated for their capacity to accomplish direct in vivo gene transfer to airway epithelium employing a rodent model. Binary complexes containing transferrin or adenovirus, or combination complexes containing both transferrin and adenovirus, were evaluated. The highest in vitro gene transfer efficiency in primary cultures of airway epithelial cells was accomplished by the combination complexes. This result was paralleled in vivo. Transient gene expression of up to 1 week was observed with localization of the transduced cells to the region of the small airways. These results establish the feasibility of this type of approach for gene therapy applications. PMID- 8461381 TI - High-level human adenosine deaminase expression in dog skin fibroblasts is not sustained following transplantation. AB - Primary skin fibroblasts are an attractive target tissue for retroviral-mediated gene therapy; however, transient expression of therapeutic genes has been a recurrent problem in several rodent models. The gradual decrease in gene expression could be tissue or species specific. To investigate the phenomenon further, human adenosine deaminase (ADA) expression was monitored in genetically modified skin fibroblasts transplanted in beagle dogs. In culture, transduced canine fibroblasts expressed high levels of human ADA activity (33.6 mumoles adenosine metabolized per hour per milligram of soluble protein) in comparison to canine ADA in untreated control cells (1.3 mumol/hr.mg protein) and for 2 weeks following transplantation, the graft contained up to four-fold more enzyme activity from human ADA than the endogenous canine enzyme. However, by 10 weeks, human ADA expression was undetectable. At the time when human ADA expression was greatly reduced, DNA analysis showed the presence of vector sequences. These results directly parallel those observed in rodent models and suggest retroviral vector inactivation is a tissue-specific rather than species-specific mechanism. PMID- 8461382 TI - Position paper on human germ line manipulation presented by Council for Responsible Genetics, Human Genetics Committee Fall, 1992. PMID- 8461383 TI - Use of two retroviral markers to test relative contribution of marrow and peripheral blood autologous cells to recovery after preparative therapy. The University of Texas M.D. Anderson Cancer Center. Division of Medicine. PMID- 8461384 TI - Long-term expression of retroviral-transduced adenosine deaminase in human primitive hematopoietic progenitors. AB - Adenosine deaminase (ADA) deficiency, a rare autosomal recessive disorder, is an ideal candidate for gene replacement therapy. By means of co-cultivation with a retroviral vector-producing cell line, we have demonstrated efficient transfer and expression of the human ADA gene into human primitive hematopoietic progenitors. At 6 weeks post-transduction in myeloid long-term bone marrow culture, approximately 50% of the clonogenic progenitors were transduced by the provirus, with ADA expression detected in 30% of transduced colonies. The ADA activity increased by 3.7-fold in the nonadherent fraction of transduced bone marrow after 9 weeks. We have also achieved efficient transduction by retroviral supernatant of normal and ADA-deficient bone marrow cells that were allowed to establish a stromal layer in long-term culture, indicating the feasibility of proceeding with attempts to perform stem cell gene therapy on patients with ADA deficiency. PMID- 8461385 TI - T-cell receptors in autoimmune disease. PMID- 8461386 TI - MHC and autoimmune diseases. PMID- 8461387 TI - Anti-CD3 antibodies. PMID- 8461388 TI - Anti-T-cell receptor V beta antibodies in autoimmunity. PMID- 8461389 TI - Vaccination with T-cell receptor peptides. PMID- 8461390 TI - From treatment of experimental allergic encephalomyelitis to clinical trials in multiple sclerosis. PMID- 8461391 TI - Human-murine chimeric CD4 monoclonal antibodies. A modern panacea for autoimmune disease? PMID- 8461392 TI - CD4 antibody therapy in chronic inflammatory dermatological diseases. PMID- 8461393 TI - Anti-class II antibody treatment in autoimmune diseases. PMID- 8461394 TI - Molecular dissection of the T-cell receptor/CD3 complex. PMID- 8461395 TI - Interleukin-2 receptor-targeted immune therapy. PMID- 8461396 TI - Anti-gamma interferon (IFN-gamma) monoclonal antibodies. PMID- 8461397 TI - Suppression of T-cell activation by administration of MHC class II-binding peptides. PMID- 8461398 TI - Thyroglobulin as autoantigen and tolerogen. PMID- 8461399 TI - Prevention of myosin-induced autoimmune myocarditis with competitor peptides. PMID- 8461400 TI - CD4, CD8, and other surface molecules regulating T-cell activation. PMID- 8461401 TI - MHC proteins and MHC peptide interactions. PMID- 8461402 TI - Monoclonal antibodies for the therapeutic induction of tolerance. PMID- 8461404 TI - Detection of muscle larvae of Trichinella spiralis by enzyme-linked immunosorbent assay. AB - ELISA was applied to the detection of Trichinella spiralis larvae in infected rat muscles. Anti-muscle larva serum was prepared by inoculating crude extract of muscle larvae to rabbits. Limb muscles of infected rats were emulsified with carbonate buffer and the supernatant was used for ELISA. ELISA values of positive muscular samples were clearly higher than those of negative ones to prove that ELISA can be applied to the detection of muscle larvae. The present method showed positive values to muscles infected with 10 or more larvae per gram of muscle (LPGM). PMID- 8461403 TI - Fine structure of the septal olfactory organ of Masera and its associated gland in the golden hamster. AB - Fine structures of the septal olfactory organ of Masera (MO) and its associated gland, a kind of olfactory glands, were examined in the golden hamster in comparison with those of the olfactory epithelium (OE) and vomeronasal organ (VNO) and their associated olfactory glands. Bipolar neurons of the MO were divided into two types according to their apical morphology, one similar to the receptors of the OE and the other to those of the vomeronasal sensory epithelium (VSE). The former was dominant and interpreted as main receptors of the MO. The other was less in number, but also regarded as a kind of olfactory receptors. The ultrastructural features of supporting cells of the MO were similar to those of the OE rather than to those of the VSE, while those of basal cells were almost in common in the OE, VSE and MO. The associated gland of the MO was positive to both PAS and alcian blue as the Bowman's gland of the OE. The fine structure of the associated gland of the MO was also similar to that of Bowman's gland. The present findings on the fine structure of the MO and its associated gland strongly suggest that the MO fulfills an olfactory function similar to that of the OE. PMID- 8461405 TI - Identification and characterization of the major carbohydrate-binding proteins in chicken serum as immunoglobulins. AB - To isolate the major carbohydrate-binding proteins in pooled normal chicken sera, affinity chromatographies on different affinity gels were carried out. From the results obtained, normal chicken sera were found to contain serum proteins which were Ca(2+)-dependently and -independently reactive with mannose, N acetylglucosamine, N-acetylgalactosamine, L-fucose, melibiose, lactose, unsubstituted Sepharose 4B, and SeaKem HE agarose. They were electrophoretically and antigenically found to be mainly IgM and IgG. PMID- 8461406 TI - Polyacrylamide gel electrophoretic mobility of alkaline proteinase produced by Aspergillus flavus isolated from a penguin. AB - The electrophoretic mobility of alkaline proteinase produced by four isolates from a penguin (Spheniscus magellanicus) was same in all of them and was consistent with that of Aspergillus (A.) flavus NRRL 1957 used as a reference strain, but not consistent with that of A. parasiticus NRRL 2999. Therefore, four isolates were confirmed as A. flavus. PMID- 8461407 TI - Hypersensitivity of LEC strain rats in radiation-induced acute bone-marrow death. AB - LEC strain rats, which have been known to develop hereditarily spontaneous fulminant hepatitis 4 to 5 months after birth, were highly sensitive to whole body X ray-irradiation as compared to WKAH strain rats. Radiation-induced acute bone-marrow death occurred at doses higher than 2.0 Gy in LEC rats, and at doses higher than 7.4 Gy in WKAH rats, respectively. By probit analysis of survival data, it was shown that the LD50/30 value for LEC rats was 3.0 Gy which was significantly lower than that (7.8 Gy) of WKAH rats. Histopathological examinations of the bone marrows from both strains after irradiation at a dose of 4.0 Gy revealed that a number of hemopoietic cells were recovered in WKAH rats on day 8 after irradiation, but not in LEC rats. These results suggested the hypersensitivity of LEC rats to ionizing radiation in connection with acute bone marrow death. PMID- 8461408 TI - Superovulation of Japanese black heifers treated with FSH-P and FSH-R. AB - The effects on superovulation in beef heifers of two kinds of porcine FSH preparations with different LH content, FSH-P and FSH-R, were compared. Forty-two heifers of the Japanese Black Breed received a total dose of 28AU of FSH-P containing 6.5% LH or FSH-R containing 0.58% LH intramuscularly, in a descending manner for four days. The mean numbers (+/- SD) of obtained ova/embryos and transferable embryos were 4.9 +/- 2.3, 1.5 +/- 0.9 and 11.2 +/- 2.4, 4.8 +/- 1.4, respectively. FSH-R treatment yielded a significantly greater number of ova/embryos and transferable embryos than FSH-P treatment (P < 0.05). PMID- 8461409 TI - The ability of Salmonella enteritidis isolated from chicks imported from England to cause transovarian infection. AB - S. Enteritidis HY-1 isolated during quarantine from chicks imported from England was used. Laying hens at the age of 34 weeks were inoculated orally with 10(10) organisms (10 birds), intramuscularly with 10(9) (5 birds), and intravenously with 10(9) (5 birds). Egg production did not change in hens infected orally, although it was reduced in hens infected intramuscularly for 2-3 weeks post inoculation. For one month, internally infected eggs of which the shells were not contaminated were found: one out of 65 eggs in hens infected orally and three out of 36 eggs in hens infected intramuscularly. This experiment demonstrated the ability of S. Enteritidis isolated from chicks imported from England to cause transovarian infection. PMID- 8461410 TI - A case of neonatal calf with meningitis associated with Klebsiella oxytoca infection. AB - A 16-days-old calf exhibited pyrexia, difficulty to stand and walk, cloudiness of the ocular aqueous humor, and swelling of the shoulder joints. The primary pathological lesion was fibrinopurulent meningitis with Gram-negative small bacilli, and which was concurrently accompanied with endophthalmitis, polyarthritis, and purulent inflammation in several visceral organs. Klebsiella oxytoca was isolated from the brain and spinal cord. These results suggest that this is a rare case of meningitis with septicemic K. oxytoca infection in neonatal calf. PMID- 8461411 TI - Comparative study on cross-reaction of leptospiral antibodies in several serological tests to detect antibodies to Borrelia burgdorferi in dogs. AB - The effects by the leptospiral antibody are described at several serological tests for the detection of the antibody to B. burgdorferi in dogs. The titers at ELISA used with the ultrasonicated bacterial antigen (US-ELISA) were related with IFA. But cross reaction with the leptospiral antibody were shown in an agglutination test. Non-specific and cross-reactions were observed in ELISA used with formalin-killed bacterial antigen. This indicates that US-ELISA is a reliable serodiagnosis method for Lyme disease in dogs in eliminating the cross reaction with leptospiral antibody. PMID- 8461412 TI - Clinostomum complanatum (Trematoda) infection in freshwater fish from fish dealers in Tottori, Japan. AB - During the period January 1989 through February 1991, 327 freshwater fish of 3 different species (Carassius cuvieri, Cobitis anguillicaudatus and Hypomesus transpacificus) purchased from 7 fish dealers in Tottori City were investigated for the metacercarial infection of Clinostomum complanatum. Among them, 20.5% (16/78) of C. cuvieri were infected with this fluke. Each infected fish harbored 1 to 30 metacercariae. The sites and rates of parasitization of metacercariae in the infected fish were 42.4% in the body muscles, 30.3% in the muscles at the pectoral fin, 21.2% in the tissues around the gills and 6.1% in the cheek muscles. PMID- 8461413 TI - Ovarian response to hCG in the postweaning sow. AB - Five non-cyclic postweaning sows were given intramuscularly 1,000 IU of hCG on day 2 (4 sows) and day 36 (1 sow) after weaning. Single or multiple follicular cysts were developed in ovaries in all cases. Plasma E2 fluctuated at low levels in 4 of 5 sows resulting in silent heat. The sows which exhibited neither estrus nor ovulation after hCG administration did not display any preovulatory LH surge, and plasma progesterone levels remained low (< or = 1 ng/ml). These results suggest that abnormal follicular growth or impairment of the ovulation process as a consequence of unsatisfactory LH release after hCG treatment in swine with ovarian inactivity may promote the formation of ovarian cysts. PMID- 8461414 TI - An electron microscopic study on follicular formation and TSH sensitivity of the fetal rat thyroid gland in organ culture. AB - Thyroids of 15-day rat fetuses prior to culture had no follicles. After 2 days in culture, regardless of added TSH in the medium, thyroids had small, colloid storing follicles. In the follicular cells, the rER and Golgi apparatus were somewhat well developed as compared with the thyroids prior to culture. Thyroids of 17-day fetuses prior to culture were first inlaid with follicles. With TSH, 2 day cultures of 17-day thyroids showed a more marked dilation of rER and a further development of Golgi apparatus than those without TSH. These results indicate electron microscopically that TSH has no effect on the first formation of follicles as well as on the initial development of follicular cells, but that TSH can promote the further development of follicular cells themselves of once developed follicles. PMID- 8461415 TI - Three cases of bovine extreme tetralogy of Fallot. AB - Three female Holstein calves having cyanosis of the visible mucous membrane, exercise intolerance and systolic murmur were examined. Extreme Tetralogy of Fallot with ventricular septal defect was confirmed at autopsy. All of the intrapericardial pulmonary arteries were completely absent in two cases. In the other case, the atretic pulmonary trunk, with a bicuspid valve, rose from a very small chamber which was located on the blind-ending muscular infundibulum. There was no connection between the atretic pulmonary trunk and the right ventricle. PMID- 8461416 TI - Platelet abnormalities in a dog suffering from gangrenous mastitis by Staphylococcus aureus infection. AB - Severe gangrenous mastitis due to Staphylococcus aureus infection was diagnosed in a 7 year-old intact female beagle which was presented with swelling of mammary glands after dystocia. Leukocytosis (25,200-48,600/microliters), decreased platelets (107,000-179,000/microliters), and abnormal platelet pattern continued during the critical condition. Consistent with platelet pattern, large platelets were observed in the blood smear. The number of leukocytes and platelets rapidly returned to normal during treatment, and the platelet pattern was also restored. The number and pattern of platelet may provide a clue for the evaluation of the clinical condition and/or severity of the lesions in the dog with mastitis. PMID- 8461417 TI - A cryptic DNA sequence, isolated from Actinobacillus pleuropneumoniae, confers a hemolytic activity upon Escherichia coli K12 strains. AB - A hemolytic recombinant clone on Escherichia coli was obtained from a genomic library of Actinobacillus pleuropneumoniae. The clone possessed a recombinant plasmid, pHLY1, carrying an insert DNA of 1 kilobases. A 21 kilodaltons protein, which is assumed to be a fusion protein with a tetracycline resistant protein of pBR322, was encoded by pHLY1. The nucleotide sequence and its deduced amino acid sequence were different from those of the previously reported hemolysin genes of A. pleuropneumoniae. Furthermore, the amino acid sequence did not show a significant homology with other published sequences in the SWISS-PROT Protein Sequence Data Bank. PMID- 8461418 TI - Epidemiologic analyses of spatial clustering of bovine ephemeral fever outbreaks. I. Application of the negative binomial distribution. AB - An epidemic that propagates through a population results in a contagious spatial pattern. The incidence per farm of bovine ephemeral fever (BEF) outbreaks in the 22 areas of Fukuoka Prefecture in 1988 was well explained by the negative binomial distribution, which is generally considered, as the clustering of the outbreaks. Furthermore, the clustering was analyzed with three categories of vaccination rate (No. 1-40%, and 40-80%). As a result, the no vaccination and high vaccination rate (41-80%) groups tended to shift to similarly the Poisson distribution. It may be speculated that an insufficient vaccination control of the BEF was influenced with the clustering. PMID- 8461419 TI - Pathological analysis of bone fractures in race horses. AB - Pathomorphological analysis was performed on fractured bones of 470 race horses. The most common fracture site was the limb (98% of cases), and the majority of fractures were intra-articular. Focal osteochondral lesions consisting of osteochondrosis, osteonecrosis and osteosclerosis were observed frequently in fractured and non-fractured bones. In the fractured bones, the lesions frequently appeared in the vicinity of the fractured site. Under the influence of antecedent osteochondrosis from the young stage, osteosclerotic and osteonecrotic lesions may have been induced by immoderate exercise and localized ischemia. These morbid conditions may be important as local predisposing factors for bone fracture because the osteosclerotic and osteonecrotic lesions may contribute to diminished resistance to torsion and shearing forces. PMID- 8461420 TI - An ultrastructural study of cutaneous hemangioma in two chickens. AB - Cutaneous hemangioma in two laying hens was examined by light and electron microscopy. In close association with capillary and cavernous hemangioma there was a solid cell mass. Ultrastructurally, the cell mass consisted of undifferentiated mesenchymal cells and had an alveolar structure. There were transitional cell types from the alveolar structure to the capillary and cavernous hemangiomas. Hemangiomatous structure may develop from the undifferentiated mesenchymal cells in the solid cell mass. PMID- 8461421 TI - Suppressed antibody response to sheep erythrocytes in experimentally Babesia rodhaini-infected mice. AB - Mice experimentally infected with Babesia rodhaini were immunized with sheep red blood cells (SRBC), and the splenic plaque forming cell (PFC) response to SRBC was investigated. Suppressed splenic antibody response to SRBC accompanied with the elevated parasitemia was recognized. This evidence suggests that an immunosuppression in B. rodhaini infection may be involved in the multiplication of parasites contributing to high mortality of mice infected with B. rodhaini. PMID- 8461422 TI - Turbidimetric-kinetic assay of endotoxin in rumen fluid or serum of cattle fed rations containing various levels of rolled barley. AB - A new, automated turbidimetric-kinetic (ATK) assay was used to quantitate bacterial endotoxin in rumen fluid or in serum of Holstein steers. The ATK method used Limulus amebocyte lysate (LAL) reagent with added beta-glucan (LAL-ES) which improved specific sensitivity to endotoxin. Design of the feeding trial permitted comparison of endotoxin levels found during consumption of a basal ration with those higher levels detected at various times following the introduction of increasing percentages of rolled barley to that basal ration. Both serum and ruminal endotoxin levels were significantly higher in steers on the higher concentrate rations. Peak endotoxin levels were detected 20 days following the change to the highest concentrate ration which contained 60% barley. Endotoxin levels from both sources subsequently decreased. Ruminal endotoxin stabilized at about 10 times the level, and serum endotoxin stabilized at 2 to 4 times the level, of that previously found during feeding of the basal ration. Test protocol included sample dilution and heating in order to avoid the effects of endotoxin inhibitors. Recovery rates for added endotoxin to either serum or rumen fluid supernates ranged from 120 to 136%. Coefficient of variation for endotoxin concentration in serum was lower than 10%, and in rumen fluid only slightly higher. There was significant correlation between ruminal concentration as measured by the ATK method and an alternative chromogenic substrate assay procedure. Changes in endotoxin level in experimental steers were those predictable from experience with naturally occurring incidents of grain engorgement. The ATK assay appears to be an accurate and rather simple technique which will prove useful for experimental and clinical studies in the future. PMID- 8461423 TI - Purification and identification of a serum protein increased by anthelmintic drugs for Dirofilaria immitis in dogs. AB - Polyacrylamide gel electrophoretic analysis of canine serum protein has revealed that the administration of anthelmintics elicits an increase in a certain serum protein. This protein, named PT60, was partially purified by ammonium sulfate fractionation and preparative electrophoresis. The purified PT60 gave a single band with the molecular size of 53 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions. After reduction with 2 mercaptoethanol, two bands appeared at 35 kDa and 17 kDa, indicating that PT60 consists of two subunits which are linked with each other by disulfide bonds. PT60 had the capacity to bind to hemoglobin. In an immunodiffusion test, an antiserum against PT60 cross-reacted with canine haptoglobin (Hp). N-terminal amino acid sequences of two PT60 subunits were identical to those of alpha and beta subunits of canine Hp, respectively. Thus, PT60 was identified as Hp. PMID- 8461424 TI - Antibody responses of Japanese horses to influenza viruses in the past few years. AB - A total of 305 horse sera collected in the Hidaka district of Hokkaido in the years 1988-90 were tested for the presence of hemagglutination-inhibition (HI) antibodies to A/equine/Newmarket/1/77 (H7N7), A/equine/Tokyo/2/71 (H3N8) and A/equine/Kentucky/1/81 (H3N8, Kentucky) strains of equine influenza (EI) virus. Antibodies to the 3 strains were detected in hardly of the 45 sera from 2-years old horses which were collected before vaccination. Many of the 51 horses, after vaccination with inactivated EI virus, had HI antibodies to the 3 strains in 37 to 88 per cent. However, the number of positive reactors among the horses aged 3 to 23 years gradually decreased with the advance in age. In particular, no antibody response was found in the 60 horses over 9 years of age, except for 3 cases with HI antibody of low titer, with the Kentucky strain which has recently been prevalent among the horse populations in many countries. In a complement fixing test, antibodies to the soluble antigen of type A influenza virus were detected in the sera collected from the horses which were exposed to an outbreak of EI virus infection, but not in the sera from the vaccinated horses examined. PMID- 8461425 TI - Referential derivation of epidural electroencephalogram in El mice. AB - Epidural EEG of 20 El mice is recorded under ketamine and xylazine anesthesia with epoxy coated silver balls as exploring electrodes. A stainless steel needle is placed subcutaneously near the nose as a reference electrode. Reproducibility of recording is remarkable. Multiple spike complex synchronizing on both frontal lobes is observed in 8 mice. Among them, small spikes preceding the multiple spike complex are also observed on the left frontal lead in 7 mice and on the right in 1 mouse. These spikes do not spread to occipital recordings. The discriminative ability of the recording is due to the coated electrode commonly employed with much larger animals and to suitable placement of the reference electrode. This simple and well known method permits the analysis of not yet satisfactorily explored the EEG of El mouse. PMID- 8461426 TI - Inhibitory effects of horse serum on immunoassay of horse ferritin. AB - The effects of horse serum on the immunoassay of horse ferritin were investigated using two sandwich enzyme-linked immunosorbent assay (ELISA) systems. In System A, affinity-purified antibody to horse spleen ferritin and its conjugate with alkaline phosphatase were used as the first and second antibodies, respectively. In System B, whole antiserum and its conjugate with the enzyme were used. The recoveries of horse spleen ferritin added to horse sera were very low in either system (50-71% in System A; 42-79% in System B). However, heat treatment of the sera at 75 degrees C for 15 min improved the recoveries (90-96%) in System A, whereas the recoveries in System B were not sufficiently improved by the same treatment (75-83%). The apparent concentrations of ferritin in adult and newborn horse sera increased after heat treatment of the samples. From these results, it is concluded that horse serum contains the heat-unstable substance(s) which inhibits the immunoassay of horse ferritin. PMID- 8461427 TI - Evaluation of phlebotomy-induced erythropoietin production in the dog. AB - Erythropoietin (EPO) production in dogs was studied by reducing red blood cells with phlebotomy. In this study, the hemoglobin reduction rate (delta %Hb) was newly taken into account as the regulating factor for EPO production, and its usefulness to estimate the stimulating intensity to EPO production was examined. As the result, plasma EPO was highly correlated with delta %Hb showing the importance related to regulation of EPO production, in the increasing plasma EPO by different degrees of phlebotomy, in the change of plasma EPO through the anemia progress and recovery period after severe phlebotomy, and in the initial variation of plasma EPO induced by chronic mild phlebotomy. On the other hand, increasing EPO production appeared at least within 6 hr after acute severe phlebotomy, which revealed significantly higher plasma level compared with the mild chronic phlebotomy, suggesting the effect of time leading to red blood cell reduction on EPO production response. Simultaneously, considering an in vivo EPO half life of 8.4 hr calculated from plasma EPO disappearance after bilateral nephrectomy, endogenous plasma EPO accumulation should be taken into consideration in rapidly increasing of delta %Hb. PMID- 8461428 TI - Distribution of T cell subsets in chicken lymphoid tissues. AB - The distributions of T cell subsets in chicken lymphoid tissues were investigated immunohistochemically using monoclonal antibodies (Lc-6, Lc-4) with specificity for chicken CD4 and CD8, respectively. In thymic tissues, CD8+ cells were found only in the cortex, while CD4+ cells were detected not only in the cortex but also in the medulla. The cortex just below the capsule demonstrated no immunoreactivity to either antibody. In the cecal tonsile, CD8+ cells were found restrictly in the subepithelial lamina propria. It was noted that the germinal centers were clearly surrounded with many CD4+ cells in the mid and deep portions of the lamina propria. In the spleen, clusters of CD8+ cells were observed only in the red pulp. Most lymphocytes in the periarteriolar lymphatic tissue and perivenous lymphatic tissue showed a CD4-positive reaction. No lymphocyte in the germinal centers reacted with these two monoclonal antibodies. No immunoreactivity for either CD8 or CD4 was detected anywhere else in the bone marrow or bursa of Fabricius. In the case of exposure to the protein antigen (alum-precipitated bovine serum albumin), CD4+ cells were demonstrated in some germinal centers, which were increased in size, while the areas expressing CD8 in the red pulp were decreased in size. These results suggest that the preferential distributions of T cell subsets are inherent in chicken lymphoid tissues. PMID- 8461429 TI - Endometriosis in cynomolgus monkeys retired from breeding. AB - Twenty-seven cases of endometriosis were found in 94 female cynomolgus monkeys retired from breeding. The ages of the affected monkeys (28.7% of all the monkeys) ranged from 11 years to 23 years of age with an average of 15.3 years. There was no significant difference in the incidence of endometriosis between groups which had or had not undergone a cesarean section. Time after the last pregnancy was significantly longer in the affected monkeys than in the non affected ones. These cases were histopathologically classified into four types: 1) pelvic endometriosis with formation of endometrial cysts (51.8% of the affected monkeys), 2) pelvic endometriosis invading other organs without formation of endometrial cysts (3.7%), 3) uterine adenomyosis (22.2%), 4) combined pelvic endometriosis and uterine adenomyosis (22.2%). PMID- 8461430 TI - Effects of surgical orthodontic treatment for malalignment due to the prolonged retention of deciduous canines in young dogs. AB - This study was conducted to clarify the effects of surgical orthodontic treatment for malalignment caused by the prolonged retention of deciduous canines in young dogs. Fifty-five dogs with malocclusion or pre-malocclusion were divided into two groups. Group 1 received surgical orthodontic treatment (32 dogs) using modification of Ross and Yamane's method of treating for malalignment due to prolonged retention of deciduous canine teeth; Group 2 received no treatment (23 dogs). Occurrence of malocclusion 1-3 weeks after treatment of the group receiving surgery was only 3.8%. However, malocclusion was seen in 73.4% of the non-treatment group approximately 2 years after the first examination. Surgical orthodontic treatment was very useful in treating malalignment due to prolonged retention of deciduous canines in young dogs. PMID- 8461431 TI - Pharmacokinetics of sulfadimethoxine in skin of broiler-chicken after single and multiple intravenous injections. AB - Pharmacokinetics of sulfadimethoxine (SDMX) in skin of broiler chicken after intravenous and in-drinking-water administrations were investigated to examine the reason for a longer residue of SDMX in the skin which was observed in the residue study after administration via drinking water at a concentration of 1,000 ppm. The decay curve of SDMX in the skin after single intravenous injection of 200 mg/kg, the highest dose, was fitted to the two compartment model with T1/2 of 4.4 hrs in the first elimination phase and 173 hrs in the second one. The extrapolated concentrations in the skin at 24 hrs after the injection were calculated to be 69.0 micrograms/g for the 1st phase and 0.11 micrograms/g for the 2nd phase. The decay curves in the skin after single injection of 30 and 100 mg/kg were fitted to the one compartment model with T1/2 of 3.2 and 5.7 hrs, respectively. Dividing a high dose into 3 to 5 doses and injecting sequentially with intervals of the previously measured T1/2, SDMX concentrations in the skin were about half of those in the plasma and ran parallel. The plasma concentration time curves after single intravenous injection of SDMX more than 100 mg/kg showed nonlinear kinetics with concentrations over 100 micrograms/ml for 12-30 hrs after the injection. By administration of SDMX via drinking water, a sustained residue curve of SDMX in the skin at 1,000 ppm reported previously was not observed at 500 ppm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461433 TI - Rumen ciliates of Ezo deer (Cervus nippon yesoensis) with the morphological comparison with those of cattle. AB - The composition of rumen ciliate protozoa was surveyed in 13 Ezo deer, Cervus nippon yesoensis, inhabiting Hokkaido, Japan. As a result, two species of the genus Entodinium, E. simplex and E. dubardi, were detected. Each Ezo deer had only a single species of protozoa, E. simplex or E. dubardi. Since E. simplex in Ezo deer had a wide variation in body size and shape, its measurements were compared with those of E. simplex, E. nanellum and E. exiguum obtained from Holstein-Friesian cattle feeding in the same area. The ciliate density ranged widely from 3.1 to 5882.4 x 10(3) with an average of 567.4 x 10(3) per 1 ml of rumen fluid. PMID- 8461432 TI - Evaluation of extravascular thermal volume in the lung in dogs with endotoxin induced shock by double indicator dilution method using heat and sodium ions. AB - Accuracy assessment was undertaken under varying hemodynamic conditions for a lung water volume measurement device which is based on the principle of a double indicator dilution method using heat and sodium ions. Changes in extravascular thermal volume were investigated in dogs with endotoxin-induced shock. The isoproterenol- or propranolol-induced changes in hemodynamics had no effect on the measurement. This confirmed the high accuracy of this measuring method. The measurement revealed a tendency for the extravascular thermal volume to gradually increase (p < 0.05) during endotoxin shock. This confirmed the gradual progression of pulmonary edema during endotoxin shock. PMID- 8461434 TI - Controlled release of proteins from 2-hydroxyethyl methacrylate copolymer gels. AB - A series of hydrogels with large pores was synthesized by the precipitation polymerization of 2-hydroxyethyl methacrylate (HEMA) with crosslinking agent in aqueous solution. Such gels are potentially useful for the controlled release of large-molecular-weight species such as proteins. In this study, the release behavior of lysozyme and alpha-amylase from hydrogels formed from HEMA or HEMA with a comonomer was studied. It was found that the polymer composition affected the total amount of lysozyme released and its activity. Effects were smaller with alpha-amylase. Charged gels, containing a phosphate moiety, released larger amounts of lysozyme at a reduced rate as a result of charge-charge interactions. PMID- 8461435 TI - Release of chemicals from polyurethane foam in the Meme breast implant. AB - Samples of polyurethane (PU) foam from the Meme breast implant were incubated at 37 degrees C in either 0.3-3.0 N sodium hydroxide (NaOH) solutions, normal saline, or methanol. The chemicals released were analyzed by gas chromatography (GC), gas chromatography/mass spectrometry (GC/MS), and Fourier-transform infra red (FT-IR) spectroscopy. The surfaces of the treated and untreated foam samples were studied by scanning electron microscopy (SEM). The NaOH solutions hydrolysed the foam, releasing toluene diamine (TDA). Incubating the foam in methanol washed out trace quantities of anti-oxidant, 2,4-dimethyl-6-t-butylphenol (DBP). When the foam was incubated in normal saline at 37 degrees C no TDA was detectable but another compound with a mass ion of 173 was detected. Further GC/MS studies confirmed that this compound was polyol, one of the reagents used to manufacture the PU foam. Repeatedly incubating or washing the foam in normal saline or methanol eliminated the release of polyol. SEM studies of the foam samples before and after incubation experiments, showed no evidence of polymer degradation. These findings indicated that polyol was present in the PU foam only as an impurity or residue and did not originate from the breakdown of the foam itself. PMID- 8461437 TI - In vitro toxicity of biomaterials determined with cell density, total protein, cell cycle distribution and adenine nucleotides. AB - Inhibition of cell growth is the most commonly used endpoint for in vitro toxicity of biomaterials. The use of several different endpoints might however generate more information concerning the nature of the toxicity. Thus, we examined the toxicity of two biomaterials, Polyvinylchloride (PVC) and Polyoximethene (POM), with different selected endpoints. The influence of cell growth on these endpoints was also investigated. Water extracts from the polymeric materials were tested on the continuous cell line L-929. Cell density, total protein, total protein per cell, fraction of cells in G0/G1- or S-phase, the concentration of ATP, ADP and AMP were used as endpoints. The PVC material did not significantly influence any of these endpoints until after 72 hours of exposure and the main part of the toxicity at 72 hours was related to higher proliferation rate in control cultures. After the cells had been incubated for 8 hour with POM the main toxic effect was on the energy parameters. In conclusion the PVC material was less toxic than the POM material. Our results also implies that the choice of endpoint will influence the evaluation of cytotoxicity. PMID- 8461436 TI - Preservation of regional and global left ventricular function by intracoronary infusion with oxygenated fluorocarbon emulsion Therox in dogs. AB - We tested the oxygen transport and delivery capacity of the novel perfluorocarbon emulsion, Therox (F44E, 1,2-bis-perfluorobutyl-ethylene) by comparing left ventricular regional and global function in dogs during perfusion of the left anterior descending coronary artery (LAD) with oxygenated Krebs buffer and oxygenated Therox emulsion (20% w/v) at 20 ml/min for two separate 3 min periods. During LAD perfusion with oxygenated Krebs buffer, complete loss of systolic wall thickening in the LAD perfusion area was observed, dP/dt was significantly reduced and left ventricular end-diastolic pressure (LVEDP) was increased. In contrast, LAD perfusion with oxygenated Therox maintained regional wall thickening at 60-70% of control and completely preserved global function as measured by dP/dt and LVEDP. Thus, Therox is an effective oxygen carrier in this animal model. PMID- 8461438 TI - Preparation and evaluation in vitro and vivo of copoly (lactic/glycolic) acid microspheres containing norethisterone. AB - Poly (lactic/glycolic) acid (PLGA) microspheres containing 20% norethisterone (NET) were prepared and the preparation methodology was optimised. The microspheres showed a slow and steady release pattern up to more than 96 hours in 27.5 wt% ethanol solution. In vivo performance of the microspheres indicated that a single intramuscular injection of 80 mg of microspheres could significantly prolong the duration of estrus suppression up to 45 days in rats. In addition, the studies on the stability of microspheres showed that there was no significant change both in the NET content of microspheres and the NET release rate in vitro after storage for one year. PMID- 8461439 TI - The long-term observation of the transplantation of encapsulated rat islets to the diabetic mice. AB - Rat islets encapsulated in the immuno-isolated membrane were transplanted intraperitoneally into 11 streptozotocin induced diabetic mice. The effective rate was 91% while all rejected in the 11 nonencapsulated xenograft group. 4 mice showed complete remission and longest normoglycemic period in those mice was 360 days. The pathological changes of islets of the long-term successful xenograft group were studied and showed atrophy. It proved that the immuno-isolated membrane can protect rejection during xeno-transplantation. PMID- 8461440 TI - Skin sensitization study of a new BIS-GMA based dental restorative material. AB - One of the criteria for the Dental Restorative Material is to not to evoke sensitization reaction when used clinically. The newly synthesized BIS-GMA based Chitra's Dental Material intended for such application was tested for skin sensitization as per the international protocol of test i.e. skin Maximization test in G.Pig. Result of this test showed conclusively that the material is devoid of sensitization potential and fit for clinical application. PMID- 8461441 TI - [Mechanics of damage and biomechanical tensile strength of the femur]. AB - The properties of the femur are represented by the micromechanics of composites and the mechanics of damage. A consideration of the femur as a composite the Young's modul is dependent on the density. The biomechanical behavior of the femur can be simulated by a one-dimensional model of the mechanics of damage. It is shown that the maximal tolerable stress and the yield stress are not direct material properties. Material behavior is determined by a damage variable that is dependent on the current strain. The results of this investigation are in good agreement with experimental results. PMID- 8461442 TI - [Rotational bending test of hydroxylapatite plasma-coated models of TiAl6V4]. AB - Plasma spraying of hydroxyapatite coatings onto hip joint and knee endoprosthesis implants and dental implants is state of the art. Nevertheless, there is still a lack of data on the long-term behavior of such coatings. Using the rotating bending test DIN 50,113 it is shown that parts plasma-sprayed with 200 microns OSPROVIT exhibit delamination only after fracture of the metallic component. At a load of 400 MPa more than 1.10(9) loading cycles were achieved. PMID- 8461443 TI - [Eye heating caused by microwave ovens]. AB - To clarify the question as to whether microwave ovens represent a risk for the eyes, a worst-case situation was investigated in which it was assumed that a child observes the internal heating process with its eyes as close to the door of a microwave oven as it is possible to get. As expected, heating of the eyes was observed, which, however, was caused mainly by the conventional heating process rather than by microwave radiation. Significant microwave heating was observed only when increased scattered radiation was simulated by inactivating the safety contacts and opening the door of the microwave oven. When the door is opened to a clearly visible gap width (2.3 cm), the contribution of the microwave component to the overall temperature increase of 5 degrees C after one hour of continuous exposure did not exceed 16%. Even at the maximum possible door gap width which just did not cause the oven to switch off automatically (2.6 cm), 15 minutes of continuous exposure contributed only 50% to the 2 degrees C temperature increase. On the basis of these results, damage to the eye through the use of microwave ovens can be excluded. PMID- 8461444 TI - [Expert system for automatic, subjective determination of refraction]. AB - An automatic system for determining a patient's subjective refraction for the fitting of glasses or contact lenses, is described. The system works without any intervention on the part of the ophthalmologist or optometrist. Directions are provided and questions asked of the patient via a loudspeaker or headphones with the aid of a computer. This computer also controls the positioning of different lenses before the patient's eyes using a phoropter, and the projection of the chart figures for visual acuity testing. The patient responds via a dedicated graphic tactile answering unit. The principles involved are described, and the experience so far gained with the method discussed. PMID- 8461445 TI - [Suture surface and suture strength of polypropylene monofilaments]. AB - Knots form the weakest sections in suture materials. The addition of forces in the knot caused by bend and tension exceed the strength of the suture material and lead to rupture in the knot. Furthermore the most pronounced tissue reactions occur in the surrounding of knots because of their relatively large surface as compared to the linear filament. With a higher knot holding capacity a secure fixation can be achieved with less knots. As a reduced number of knots leads to a smaller surface a reduced tissue reaction can be expected. Because of high rigidity and a low coefficient of friction synthetic monofilaments achieve only a low knot holding capacity. To improve the knot holding capacity a usually large number of knots is being used. With increasing surface of exogenous materials the extent of foreign-body reactions increases, e.g. formation of granuloma. Results of in-vitro experiments are reported that were conducted to identify the smallest secure knot in polypropylene filaments of various diameters. PMID- 8461446 TI - [Safety testing of high frequency surgery neutral electrodes (measuring instrument for impedance and temperature increase with AAMI-HF18 standard load)]. AB - A new safety tester device for surgical grounding plates is described. This device can measure impedance distribution and temperature increase under a standard load in accordance with the AA-MI-HF18 standard. Apart from relevant information about the grounding plates under test, possible risks for the patient can also be demonstrated. PMID- 8461447 TI - Exhaustive conformational search and simulated annealing for models of lattice peptides. AB - We consider simple lattice models for short peptide chains whose states can be exhaustively enumerated to find the lowest energy conformation. Using these exact results and numerical simulations, we compute the distributions for the mean time tN, required to find the global minimum energy state by simulated annealing (SA), as a function of N, the number of units in the chain. On the basis of scaling arguments, the time tN, to find the global minimum energy of longer chains, beyond the range covered by exhaustive enumeration, can be estimated. On the basis of the observed exponential increase in folding time of the standard SA algorithms, it is imperative that better algorithms be found for minimizing longer chains. PMID- 8461449 TI - A model for the dynemicin-A cleavage of DNA using molecular dynamics simulation. AB - Molecular dynamics (MD) simulations to model possible reaction pathways of the dynemicin-A-DNA cleavage mechanism were performed. Two base-pairs sequences, ApCpTpApCpTp-3'/TpGpApTpGpAp-5' and CpApCpGpGpGp-3'/GpTpGpCpCpCp-5', were considered in the calculations. A model based on a prior study of intercalation of dynemicin-A and posterior activation of the drug was assumed in this study. The minimum energy minor groove intercalation complexes for dynemicin-A were used as starting structures in the MD simulations for the reactive intermediate species involved in the postulated action mechanism. The dynemicin-A diol derivative product of the opening of the epoxy ring was used as a "steric mimic" ligand for the DNA-reactive diaryl intermediate. The calculated changes in the geometry of the intercalation complex, due to the opening of the epoxy ring, correspond to the approach of the postulated intermolecular reaction centers in the intercalation states that are responsible for the highest observed DNA cleavage frequency observed. Conversely, unfavorable reaction geometries were found for the intercalation modes corresponding to the lowest observed DNA cutting frequencies. PMID- 8461448 TI - Persistence analysis of the static and dynamical helix deformations of DNA oligonucleotides: application to the crystal structure and molecular dynamics simulation of d(CGCGAATTCGCG)2. AB - A theory and graphical presentation for the analysis of helix structure and deformations in oligonucleotides is presented. The parameters "persistence" and "flexibility" as defined in the configurational statistics of polymers of infinite length are reformulated at the oligonucleotide level in an extension of J. A. Schellman's method [(1974) Biopolymers, Vol. 17, pp. 217-226], and used as a basis for a systematic "Persistence Analysis" of the helix deformation properties for all possible subsequences in the structure. The basis for the analysis is a set of link vectors referenced to individual base pairs, and is limited to sequences exhibiting only perturbed rod-like behavior, i.e., below the threshold for supercoiling. The present application of the method is concerned with a physical model for the angular component of bending, so the link vectors are defined as the unit components of a global helix axis obtained by the procedure "Curves" of R. Lavery and H. Sklenar [(1988) J. Biomol. Struct. Dynam., Vol. 6, pp. 63-91; (1989) ibid., Vol. 6, pp. 655-667]. A discussion of the relationship between global bending and relative orientation of base pairs is provided. Our approach is illustrated by analysis of some model oligonucleotide structures with intrinsic kinks, the crystal structure of the dodecamer d(CGCGAATTCGCG)2, and the results of two molecular dynamics simulations on this dodecamer using two variations of the GROMOS force field. The results indicate that essentially all aspects of curvature in short oligonucleotides can be determined, such as the position and orientation of each bend, the sharpness or smoothness, and the location and linearity of subsequences. In the case of molecular dynamics simulations, where a Boltzmann ensemble of structures is analyzed, the spatial extent of the deformations (flexibility) is also considered. PMID- 8461450 TI - Synthetic peptide and template-assembled synthetic protein models of the hen egg white lysozyme 87-97 helix: importance of a protein-like framework for conformational stability in a short peptide sequence. AB - In the native structure of hen egg white lysozyme (HEL), the amino acid sequence 87-97 (HEL 87-97) forms an amphiphilic helix, with hydrophilic residues in the sequence directed toward the solvent. A synthetic version of the HEL 87-97 sequence (with the cysteine corresponding to position 94 of HEL replaced by alanine) displays conformational features in solution typical of an unordered structure as judged by CD. However, various modifications in the sequence result in increased helix-forming potential of the HEL 87-97 analogues. Further stabilization of the helical conformation in the most helical analogue of the HEL 87-97 sequence is obtained when 4 copies of this peptide sequence are coupled on a peptide carrier molecule following the template-assembled synthetic protein (TASP) approach [M. Mutter and S. Vuilleumier (1989) Angew. Chem. Int. Ed. Engl., Vol. 28, pp. 535-554 "A Chemical Approach to Protein Design-Template-Assembled Synthetic Proteins (TASP)." This suggests that long-range interactions of the peptide with its environment contribute to conformational stability in short peptide sequences. TASP molecules may prove useful for the study of the factors that determine secondary structure formation in short peptides by providing a protein-like framework. PMID- 8461451 TI - Accommodation of a D-Phe residue into a right-handed 3(10)-helix: structure of Boc-D-Phe-(Aib)4-Gly-L-Leu-(Aib)2-OMe, an analogue of the amino terminal segment of antiamoebins and emerimicins. AB - The crystal structure of the nonapeptide Boc-D-Phe-Aib-Aib-Aib-Aib-Gly-Leu-Aib Aib-OMe (I), which is an analogue of the N-terminal sequence of antiamoebins and emerimicins, establishes a completely 3(10)-helical conformation with seven successive intramolecular 4-->1 hydrogen bonds. The average, phi,psi values for residues 1-8 are -59 degrees and -32 degrees, respectively. Crystal parameters are C47H77N9O12, space group P1, a = 10.636 (4) A, b = 11.239 (4) A, c = 12.227 (6) A, alpha = 101.17 (4) degrees, beta = 97.22 (4) degrees, gamma = 89.80 (3) degrees, Z = 1, R = 5.95% for 3018 data with magnitude of F0 > 3 sigma(F), resolution 0.93 A. The use of the torsion angle kappa = C(i-1)N(i)C alpha(i)C beta(i), where kappa = 68 degrees for D-Phe and kappa = 164 degrees for L-Leu, confirms the opposite configurations of these residues. The phi,psi values of -62 degrees and -32 degrees at D-Phe are unusual, since this region is characteristic of residues with L configurations. Peptide I possesses only two chiral residues of opposing configuration. The observed right-handed 3(10)-helical structure suggests that helix sense has probably been determined by the stereochemical preferences of the Leu residue. PMID- 8461452 TI - Synthesis, conformation, and activity of HCO-Met-delta Z Leu-Phe-OMe, an active analogue of chemotactic N-formyltripeptides. AB - In order to induce a beta-turn conformation into the chemotactic linear tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), the new analogue N-formyl-L-methionyl-delta Z leucyl-L-phenylalanine methyl ester [delta Z Leu]2fMLP-OMe (1) has been synthesized. The conformational and biochemical consequences of this chemical modification have been determined. Analogue 1 has been synthesized by using N-carboxy-(Z)-alpha,beta-didehydroleucine anhydride as key compound to introduce the unsaturated residue at the central position of the tripeptide 1. The x-ray analysis shows that 1 adopts in the crystal a type II beta-turn conformation in which the new residue occupies the (i + 2) position, and an intramolecular H bond is formed between the formylic oxygen and the Phe NH. 1H-nmr analysis based on nuclear Overhauser effect measurements suggests that the same folded conformation is preferred in CDCl3 solution; this finding is also supported by molecular dynamics simulation. The biological activity of 1 has been determined on human neutrophils (polymorphonuclear leukocytes) and compared to that shown by fMLP-OMe. Chemotactic activity, granule enzyme release, and superoxide anion production have been determined. Analogue 1 is practically inactive as chemoattractant, highly active in the superoxide generation, and similar to the parent in the lysozyme release. The conformational restriction imposed on the backbone by the presence of the unsaturated residue is discussed in relation with the observed bioselectivity. PMID- 8461453 TI - Molecular dynamics simulations of B-DNA: an analysis of the role of initial molecular configuration, randomly assigned velocity distribution, long integration times, and nonconstrained termini. AB - Molecular dynamics simulations of three DNA sequences using the AMBER 3.0 force field were performed with implicit inclusion of water through a distance dependent dielectric constant and solvated counterions. Simulations of the self complementary DNA dodecamer d(CGCGAATTCGCG) were started from a regular B-DNA structure and the x-ray single crystal B-DNA structure. Although mean convergence during the 89-ps calculation was confirmed, localized differences in backbone torsionals and base-pair helicoidals were observed. A nanosecond simulation of the nonself-complementary 14 base-pair DNA d(GGCGGAATTGGCGG) indicates that most structural parameters stabilize within the first 100-200 ps, while isolated features show low-frequency oscillations throughout the calculation. The lack of harmonic constraints on the ends of the molecules was shown not to perturb the structural dynamics of the internal oligonucleotide beyond the external 2 base pairs. Comparison of three simulations of the nonself-complementary 14 base-pair DNA d(GGCGAAATTCGCGG), identical in all respects other than the assignment of initial Maxwellian atomic velocity distributions, revealed the inherent systematic variability. The three calculations result in nearly superimposable global structures, with localized variations in torsionals and helicoidals. Our results provide a basis for performing a comparative analysis of the effect of DNA sequence on localized structure. PMID- 8461454 TI - Calcium-dependence of laminin binding to phospholipid membranes. AB - Laminin is the most abundant noncollagenous protein in basement membranes. Its self-assembly has been studied in solution, and it has been established that calcium ions induce partially reversible aggregation. The behavior at a lipid membrane surface is of greater biological significance, but it is difficult to study quantitatively binding kinetics at a surface. The present work uses a powerful new integrated optics technique to measure the absorption and aggregation of the laminin-nidogen at a bilayer lipid membrane surface. It is found that the binding of a single layer of laminin at the lipid membrane is independent of the presence of calcium, but that the building up of multilayer laminin membranes requires calcium, and that these may not be destroyed by a calcium-complexing agent. PMID- 8461455 TI - Looking into the grooves of DNA. AB - The present study is aimed at understanding the effects of DNA sequence, local conformation, and curvature on groove geometry. Energy-optimized structures are obtained by Jumna methodology; groove geometry is analyzed by a recently developed technique that allows an accurate and continuous measurement of width and depth. The mechanics of groove deformations is also studied and analyzed in terms of helicoidal parameters. PMID- 8461456 TI - Helix promotion in polypeptides by polyols. AB - The helix content of [L-Lys(Me3)]n.ClO4 and [L-Lys(Me3)50,L-Ala50]n.ClO4 in water is markedly increased by the presence of sucrose and glycerol. For [L Lys(Me3)]n.ClO4 the ellipticity at 222 nm changes from +2 x 10(3) deg cm2 dmole-1 in water to -44 x 10(3) in 50% glycerol. Sucrose does not promote helix formation in melittin at pH 7.2, but glycerol does. At pH 5.5 sucrose and, more so, glycerol, induce helix in melittin. Glycerol induces some helix in methylated melittin, but less than in melittin. The results are discussed in relation to excluded volume effects, delta G of transfer of peptide and hydrophobic groups from water to mixed solvents, electrostatic effects, and preferential hydration. PMID- 8461457 TI - Ca(2+)-induced conformational transitions of phosphorylated peptides. AB - CD spectroscopic studies on protected peptides containing lysine and serine, or phosphoserine, and on serine-containing fragments of the neurofilament protein midsized subunit, both in the unphosphorylated and phosphorylated form, are reported. The introduction of the phosphoryl group was not found to have a significant spectral effect in aqueous solution. In trifluoroethanol (TFE), spectral shifts toward unordered (type U) spectra or the appearance of distorted spectra likely reflect the adoption of aperiodic polypeptide conformations due to salt bridge(s) between negatively charged phosphoserine and positive lysine side chain groups. A turn-stabilizing effect of phosphorylation was also observed. CD monitored titration experiments in TFE revealed a high conformational sensitivity of phosphopeptides toward Ca2+ ions. The appearance of the unordered spectra or spectral shifts were the sign of a bulk disordering effect of Ca2+ ions. Spectra with specific spectroscopic features reflect the formation of Ca2+ complexes and the adoption of ordered unique backbone conformations. When ordered structures were obtained on addition of Ca2+ ions, the observed CD curves showed a resemblance to the spectrum of beta-pleated sheets. This may originate from chain extension and the formation of beta-pleated sheet segments fixed by Ca2+ bridges between PO3H-1 groups of adjacent peptide chains. The data clearly show that the effect of the Ca2+ ions is highly specific: the sequence, chain length, presence and distribution of charged side-chain groups, degree and site of phosphorylation, and environmental factors appear to be determining in the process of chain extension or beta-sheet formation. PMID- 8461458 TI - Cytokine treatment of inherited bone marrow failure syndromes. PMID- 8461459 TI - Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia. AB - Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder of infancy and childhood presenting with isolated thrombocytopenia that progresses to marrow failure. The defect in thrombopoiesis is not well understood nor is the etiology of the progressive marrow failure. No standard modality of treatment exists. Here, we evaluated the capacity of marrow cells isolated from five patients with AMT and progressive marrow failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro studies demonstrated assayable numbers of CFU-MK from all patient bone marrows that responded in vitro to the addition of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM CSF), or the combination of both. These findings suggest that the defect in AMT might be partially correctable by the administration of these cytokines. A Phase I/II trial of in vivo administration of these same hematopoietins in the identical patients was conducted in which no significant toxicity was observed. IL-3 but not GM-CSF administration resulted in improved platelet counts in two patients and decreased bleeding and transfusion requirement in the remaining three. No clinical benefit was observed when GM-CSF was administered after IL-3 pretreatment. Prolonged IL-3 administration has resulted in platelet increases in an additional two patients. In vitro responsiveness of CFU-MK to either cytokine did not predict the degree of clinical response. Although the optimal dose and schedule of IL-3 either alone or in combination remains to be established, this study suggests that IL-3 may contribute to the treatment of patients with AMT. PMID- 8461460 TI - Subunit structure of the erythropoietin receptor analyzed by 125I-Epo cross linking in cells expressing wild-type or mutant receptors. AB - To analyze the structure of the murine erythropoietin receptor (EpoR), wild-type or mutant EpoR cDNAs were expressed in cell lines, and the proteins that cross linked with 125I-labeled erythropoietin (Epo) were analyzed by immunoprecipitation using an antibody against the intracellular region of the cloned EpoR. COS-7 cell transfectants expressing the wild-type EpoR showed two major cross-linked species of 145 and 110 Kd, both of which were recognized by the antibody against the cloned EpoR after denaturation under reducing conditions. Furthermore, a reduction in sizes of both cross-linked bands was observed in COS-7 transfectants expressing a mutant receptor with an internal deletion, thus indicating that both species contain the cloned EpoR. COS-7 cells expressing mutant receptors with carboxy-terminal deletions showed cross-linked bands corresponding to the smaller species of the two observed in cells expressing the wild-type receptor. In contrast to COS-7 cell transfectants, DA3 cells expressing wild-type or mutant EpoR cDNAs showed an additional cross-like species of 130 Kd. The size of this species was not altered by deletions in EpoR, showing that it did not contain EpoR. The 130-Kd cross-linked band, which would contain a 95-Kd protein, was also observed in a murine erythroleukemia cell line, D1B. These results suggest that Epo associates with a second component of 95 Kd, which is specifically expressed in hematopoietic cells. PMID- 8461461 TI - Pre-CFU-S quiescence and stem cell exhaustion after cytostatic drug treatment: protective effects of the inhibitory peptide pGlu-Glu-Asp-Cys-Lys (pEEDCK). AB - Pre--CFU-S are characterized by their ability to generate spleen colony-forming cells (CFU-S) and by their ability to repopulate the hematopoietic system after damage. We have investigated their response to three consecutive injections of cytosine arabinoside (ara-C), given at t = 0, 12, and 20 hours. Nine hours after treatment, the number of CFU-S and pre--CFU-S was reduced to 10% or 30%, respectively. No pre--CFU-S were in S-phase at this time, indicating that the pre -CFU-S losses were not caused by direct drug killing. Up to 1 year after treatment, pre--CFU-S were still depleted to 10% of normal, indicating that their proliferative quiescence was permanent. We have previously shown that inhibition of CFU-S recruitment with pGlu-Glu-Asp-Cys-Lys (pEEDCK) makes them ara-C resistant and prevents their decimation. We now found that this also prevented the excessive drainage of the pre--CFU-S pool, suggesting that pre--CFU-S allocation into active hematopoiesis is triggered by the CFU-S deficit. pEEDCK may thus be applicable as a protector of the hematopoietic repopulation potential against cytostatic drug-induced aplasia. Postchemotherapeutic stimulator treatment with (pEEDCK)2-dimer did not ameliorate pre--CFU-S losses. Long-term culture-initiating cells (LTC-ICs) showed a similar pattern of irreversible reduction after cytostatic drug treatment, which could be prevented by pEEDCK. Our results suggest, that certain subclasses of hematopoietic stem cells (pre- CFU-S) are permanently quiescent and exhaustible and that the capacity for self renewal is not a necessary property of all stem cell-like cells. PMID- 8461462 TI - Lasting safe interruption of endarterectomy thrombosis by transiently infused antithrombin peptide D-Phe-Pro-ArgCH2Cl in baboons. AB - To evaluate the relative antithrombotic efficacy and hemostatic safety of antithrombin therapy for vascular thrombus formation at sites of mechanical vascular injury, we administered the potent and specific irreversible synthetic antithrombin D-PHE-PRO-ARG chloromethyl ketone (D-FPRCH2Cl) after performing carotid endarterectomies in baboons. The continuous intravenous infusion of D FPRCH2Cl, 100 nmol/kg per minute for 1 hour, abolished acute carotid endarterectomy thrombosis for at least 48 hours. The plasma level of D-FPRCH2Cl during the infusion was maintained steady at 7.2 +/- 0.9 mumol/L, but decreased rapidly after discontinuing its infusion (T50 17 minutes). Platelet deposition, measured in real time using autologous 111In-platelet scintillation camera imaging, was 1.51 +/- 0.40 x 10(8) platelet/cm in the 14 treated animals 90 minutes postoperatively, compared with 11.7 +/- 1.16 x 10(8) platelet/cm in 14 heparin-treated controls (P < .002). The antithrombotic benefit was equivalent for treatment begun either 5 minutes before (nine animals) or 15 minutes after (five animals) reestablishing flow in the operated vessel, ie, 1.59 +/- 0.36 x 10(8) platelet/cm versus 1.35 +/- 0.51 x 10(8) platelet/min, respectively; P > .5. Endarterectomy thrombosis remained decreased for at least 48 hours postoperatively, as determined by the ratio between net 111In-platelet radioactivity at the endarterectomized site versus whole blood (ratio 0.82 +/- 0.25 in the treatment group v 3.03 +/- 0.51 in heparin controls at 90 minutes, P < .005; and 0.85 +/- 0.23 v 3.25 +/- 0.48 at 48 hours, P < .002). The marked reduction in endarterectomy thrombosis in treated animals at 48 hours was confirmed by scanning electron microscopy. Thrombin activity formed rapidly and became immediately bound to thrombus on thrombogenic segments in untreated control studies; treatment with D-FPRCH2Cl irreversibly inactivated the thrombus bound thrombin. Hemostatic function, as measured by bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) was impaired throughout the intravenous administration of D-FPRCH2Cl (BT > 30 minutes, APTT > 150 seconds, PT > 50 seconds); BT, APTT, and PT values were normal 30 minutes after discontinuing the infusions. As expected, blood loss into the surgical wound was substantial in nine animals receiving therapy initiated before restoring flow in the operated vessel (mean 95 mL, range 45 to 130 mL). By contrast, beginning D-FPRCH2Cl therapy in five animals 15 minutes after restoring arterial flow, a time when surgical hemostasis had been achieved, prevented excessive blood loss (mean 15 mL, range 10 to 35 mL; P < .01 compared with earlier treatment) without compromising the antithrombotic effects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8461463 TI - Antithrombotic properties of a dermatan sulfate hexadecasaccharide fractionated by affinity for heparin cofactor II. AB - The relationship between the antithrombotic activity of dermatan sulfate (DS) in vivo and its catalytic effect on the inhibition of thrombin by heparin cofactor II (HC II) in vitro was investigated. DS was depolymerized by Smith degradation and the fragments obtained were separated by gel filtration. The fragment of minimal size with full catalytic activity was a hexadecasaccharide, which was further fractionated by affinity for immobilized HC II. Only a small proportion by weight (6.7%) was recovered in the high-affinity fraction, which had about 10 times more catalytic activity than the unfractionated oligosaccharide; the change in activity was primarily caused by the removal of inert materials, recovered in the low-affinity fraction. 1H-NMR spectra indicated strengthening of the signal given by Ido A (2S04) in the high-affinity fraction compared with that of the low affinity fraction. The anticoagulant activity of the high-affinity fraction was exclusively HC II-dependent. The antithrombotic potency was evaluated in rabbits using the Wessler-thromboplastin model. Half-maximal prevention of thrombosis was obtained after injection of 250 micrograms/kg DS, of 500 micrograms/kg hexadecasaccharide, or of 60 micrograms/kg of its high-affinity fraction. The low affinity fraction was ineffective at the highest dose tested (1,200 micrograms/kg) and did not potentiate the effect of the high-affinity fraction. These results show that the antithrombotic effect of DS is essentially dependent on HC II binding and activation and that HC II is therefore a suitable target for antithrombotic drugs. PMID- 8461464 TI - Platelet interactions with fibronectin: divalent cation-independent platelet adhesion to the gelatin-binding domain of fibronectin. AB - Divalent cation-dependent platelet adhesion to fibronectin (FN) is mediated by the integrin receptors alpha 5 beta 1 (GP Ic-IIa) and alpha IIb beta 3 (GP IIb IIIa), which recognize the RGD (Arg-Gly-Asp) sequence in the cell-binding domain. However, FN can also support divalent cation-independent platelet adhesion. To determine which domain of FN mediates divalent cation-independent adhesion, proteolysis with thermolysin and affinity chromatography were used to isolate the cell-binding, gelatin-binding, and heparin-binding domains of FN. Unactivated and thrombin-activated platelets adhered to intact FN and the 45-Kd gelatin-binding domain in the presence of either Ca2+ or EDTA. Platelet spreading was mediated only by the 105-Kd cell-binding domain and required divalent cations. The heparin binding domains did not support platelet adhesion. Reduction of intrachain disulfide bonds or removal of carbohydrate side chains on the gelatin-binding domain did not alter the ability to support platelet adhesion. Divalent cation independent adhesion to the 45-Kd gelatin-binding domain was not inhibited by RGDS (Arg-Gly-Asp-Ser) synthetic peptides or monoclonal antibodies (MoAbs) directed against known platelet receptors. We conclude that platelets can adhere but not spread on the gelatin-binding domain of FN by a novel divalent cation independent mechanism. PMID- 8461465 TI - Human platelet aggregation by murine monoclonal antiplatelet antibodies is subtype-dependent. AB - Twenty murine monoclonal antibodies (MoAbs) generated against different human platelet antigens induced clumping of human platelets in plasma and buffer. Whereas one MoAb could agglutinate platelets, clumping for 19 MoAbs was blocked by metabolic inhibitors, indicating that these induce platelet activation. Fifteen MoAbs were of IgG1, two of IgG2a, and two of IgG2b subtype. F(ab')2 fragments of these did not evoke an aggregatory response, but specifically inhibited aggregations by and binding of their respective intact MoAbs to platelets. Single-platelet counting technology indicated that the MoAbs bind through their antigen-binding and Fc domains mainly to the surface of the same platelet, rather than cause interplatelet-binding. Despite these similarities, the mechanism of action was nevertheless subtype-dependent. Aggregation induced by all IgG1 antibodies could consistently be prevented by blocking the Fc gamma II-receptor, whereas aggregations induced by all IgG2 antibodies still occurred with blocked Fc-receptor, provided functional complement was present. We therefore conclude that platelet activation by MoAb-binding is initiated by antigen recognition followed by an Fc domain-dependent step, which involves the Fc gamma II-receptor for IgG1-type MoAbs and complement-binding for IgG2-type MoAbs. Thus, antibodies of different subtypes can aggregate platelets via different pathways. PMID- 8461466 TI - Protein S deficiency in men with long-term human immunodeficiency virus infection. AB - Decreases in protein S levels have recently been reported in some human immunodeficiency virus (HIV)-infected patients. To examine predisposing factors, 25 men randomly selected from a long-term study of HIV-infected patients were studied. The minimum mean duration of HIV seropositivity in this group was 106.6 months (range 15 to 143 months). No patients were anticoagulated at the time of the study. Three of the 25 randomly selected patients gave a history of thrombosis, in each instance occurring after the onset of HIV positivity. Two of the 3 patients with thrombosis had more than one episode. Coagulation studies showed that 3 of 3 (100%) of the patients with thrombosis and 16 of 22 (72.7%) of those without previous thrombosis had decreased free protein S. Mean-free and total protein S levels were statistically lower for HIV-infected patients with and without previous thrombosis compared with healthy male controls. C4b-binding protein was not increased in study patients with decreased protein S levels. Decreases in protein S levels did not correlate with CD4+ cell levels, CDC class, p24 antigen positivity, zidovudine (AZT) use, or Pneumocystis carinii prophylaxis. The duration of disease statistically correlated with decreases in protein S levels (r = .37, P < .05). A linear correlation existed between increasing IgG anticardiolipin antibody levels and decreasing free protein S antigen (r = .67, P < .005). This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. The data suggest that protein S deficiency is not correlated with HIV disease severity but may predispose patients to thromboembolic complications. PMID- 8461467 TI - Complement and virus-specific antibody-dependent infection of normal B lymphocytes by human immunodeficiency virus type 1. AB - We tested the susceptibility of human purified, normal B lymphocytes to human immunodeficiency virus type 1 (HIV-1) infection, in the presence or absence of complement-sufficient serum and of virus-specific antibodies. Virus replication was detected when cells were infected in the presence of both complement and anti HIV antibodies (C'-ADE conditions), by day 2 postinfection. Similar results were obtained when B lymphocytes were purified either from peripheral blood (three healthy donors) or from tonsils (four individuals with chronic tonsillitis). HIV infection was shown by polymerase chain reaction (PCR) detection of proviral sequences (gag and pol genes), by p24 antigen synthesis, and by cocultivation assay with MT2 cells. The higher p24 production was obtained when B cells were preactivated for 2 days by phorbol 12-myristate 13-acetate (PMA) before infection and then cultured in the presence of low-molecular weight B-cell growth factor (LMW-BCGF). Expression of virus envelope glycoprotein (gp) 120 could also be detected on a subpopulation of B cells (CD19+, CD22+) by flow cytometry. Blocking experiments with monoclonal antibodies (MoAbs) against CD4, CD21 (complement receptor 2 [CR2]), CD35 (CR1), CD19, and CD5 surface molecules indicated that infection of B cells involves CD4, CD21, and CD35 antigens. Indeed, blocking of CD4 receptor inhibited 10% of p24 production, and blocking of both CD21 and CD35 led to extinction of p24 signal. CR-dependent pathway is thus a major route for C'-ADE of HIV infection in normal B cells. Our results emphasize the importance of studying interactions between HIV and the complement system for better understanding infection mechanisms and the major dysfunctions of B cells in HIV infected individuals. PMID- 8461468 TI - Enrichment of interleukin-2-responsive natural killer progenitors in human bone marrow. AB - Natural killer (NK) cells can be cultured in interleukin-2 (IL-2)-containing medium from selected human bone marrow (BM) cells obtained after the elimination of mature T and NK cells. To isolate and characterize IL-2-responsive NK progenitors in the selected BM cells, we investigated the expression of IL-2 receptors (IL-2R) on these cells. Neither CD25 (IL-2R alpha) nor IL-2R beta antigen was observed on the selected BM cells before culture. However, CD25+ cells without detectable levels of IL-2R beta antigen appeared 24 hours after culture in IL-2-containing medium. Cells were sorted from each fraction of the selected BM cells 24 hours after culture after staining with anti-CD33, anti CD34, and anti-CD25 monoclonal antibodies. The generation of NK cells (CD3- CD56+ cells) and NK activity were observed only from the CD33-/CD34-/CD25+ cell fraction after culture in IL-2-containing medium. The frequency of IL-2 responsive NK progenitors relative to the fraction was 1/231 (95% confidence range, 1/156 to 1/289), which corresponded to the frequency relative to the total number of selected BM cells when the frequency relative to the CD33-/CD34-/CD25+ cell-fraction was converted according to the percentage of these cells in the total number of selected BM cells. These results indicated that IL-2-responsive NK progenitors were enriched in the CD33-/CD34-/CD25+ cell fraction. PMID- 8461469 TI - Mechanism of the chromosomal translocation t(14;18) in lymphoma: detection of a 45-Kd breakpoint binding protein. AB - The translocation t(14;18) between the BCL-2 oncogene and the Ig heavy chain (IgH) gene provides the molecular basis for the development of follicular lymphomas. The illegitimate recombination occurs in early B cells. While V(D)J recombinase is most likely involved on the chromosome 14 part, little is known about the mechanism of breakage on chromosome 18. We investigated the BCL-2 breakpoint regions for their structural vulnerability and protein binding capacity. We found that the major breakpoint region (mbr) contains an S1 nuclease sensitive site and is the target of an endogenous nuclease present in early B cells. A 45 Kd nuclear protein (bp45) from early B cell extracts binds to a homopurine-homopyrimidine stretch (GGGAGGACGGGAGGAAGGCG) in the mbr, which is homologous to a recombinatorial element in Escherichia coli (CHI). The protein also binds to homologous sequences in the minor breakpoint cluster region (mcr) and in the IgH locus. The localization of the binding sites on both chromosomes as well as the tissue distribution of bp45 suggest that this protein-DNA interaction is involved in the translocation t(14;18). The DNA binding motif is also present at other translocation breakpoints indicating a more general role for this mechanism. PMID- 8461470 TI - Induction of monocytic differentiation and tumorigenicity by v-Ha-ras in differentiation arrested hematopoietic cells. AB - Activated ras genes are often associated with human myeloid leukemias with a monocytic differentiated phenotype. To investigate the role of the activated ras gene in leukemogenesis, a myeloid nontumorigenic cell line (FDC-P1) was infected with a selectable retroviral vector carrying the v-Ha-ras gene (H1neo). Infected FDC-P1 cells were not only tumorigenic, but also showed increased monocytic differentiation in vitro. Monocytic differentiation and tumorigenicity in vivo were correlated with several-fold increased levels of activated ras gene expression. Tumorigenic cells were arrested with respect to monocytic marker expression at a much later stage of macrophage differentiation than the parental noninfected FDC-P1 cells. These data thus suggest a model of how activated ras genes could be involved in the preferential induction of hematopoietic malignancies with a myelomonocytic phenotype. PMID- 8461471 TI - Myeloid but not lymphoid cells carry the 5q deletion: polymerase chain reaction analysis of loss of heterozygosity using mini-repeat sequences on highly purified cell fractions. AB - Interstitial deletions of the long arm of chromosome 5 are among the most characteristic abnormalities observed in myeloid disorders. To assess the lineage involvement of peripheral blood cells from patients with a 5q--anomaly, purified neutrophils, monocytes, T lymphocytes, and B lymphocytes were analyzed for loss of heterozygosity using six different highly polymorphic mininucleotide and dinucleotide (CA) repeat sequences from the 5q31 to 5q33 region. Ten patients were screened by polymerase chain reaction (PCR) amplification and proved to be informative for at least one marker. Six patients showed a complete or partial disappearance of an allele in myeloid cells, whereas cells of lymphoid lineages exhibited full heterozygosity. The other patients displayed no allelic loss, indicating that the informative markers were located outside the deleted chromosomal segments. In addition, three female patients who were also polymorphic for the BstXI site in the PGK-1 gene were analyzed for the methylation status of this gene. Clonality of hematopoiesis, as determined by non random X-chromosome inactivation, followed the same cell pattern as the 5q specific allelic losses. In conclusion, using tumor-specific and clonal markers, we have demonstrated that the 5q- anomaly is restricted to cells of myeloid origin, leaving lymphoid cells unaffected. PMID- 8461472 TI - Dietary omega-3 fatty acids lower levels of platelet-derived growth factor mRNA in human mononuclear cells. AB - Platelet-derived growth factor (PDGF) is a potent mitogen thought to propagate atherosclerosis and other proliferative or inflammatory diseases. Some of these diseases are ameliorated in humans by ingestion of omega-3 fatty acids. We investigated mRNA expression of both PDGF-A and PDGF-B in quiescent peripheral blood mononuclear cells from healthy male volunteers. For this, a highly sensitive, quantitative polymerase chain reaction strategy (3n-PCR) was developed. In contrast to granulocytes, both PDGF-A and PDGF-B mRNAs are expressed in mononuclear cells. This expression occurs at a remarkably constant rate. Moreover, effects of 7 g/d of a 85% omega-3 fatty acid fish oil concentrate were investigated in a 6-week controlled, randomized, observer-blind study in 14 human volunteers, 7 of whom served as controls. omega-3 Fatty acids increased in mononuclear cell phospholipids. We demonstrate for the first time that diet affects human gene regulation. Dietary omega-3 fatty acids downregulate gene expression of both PDGF-A (-66%), and PDGF-B (-70%). This may represent a novel mechanism for the antifibrotic and antiatherosclerotic action of omega-3 fatty acids. PMID- 8461473 TI - Allogeneic blood transfusion-induced enhancement of tumor growth: two animal models showing amelioration by leukodepletion and passive transfer using spleen cells. AB - Allogeneic blood transfusions have been reported to induce immunomodulation in recipients of blood products. While the mechanism(s) of this immunomodulatory effect is unknown, it has been suggested that this effect of allogeneic blood transfusions could adversely affect patients with a malignant disorder. These concerns have been supported by a number of nonrandomized, mainly retrospective, clinical studies which indicate that allogeneic blood transfusions can adversely affect prognosis following the surgical treatment of oncology patients. Recently, we have shown that allogeneic blood transfusions enhance primary tumor growth and increase metastatic pulmonary nodule formation in inbred mice. The tumor growth promoting activity of allogeneic blood transfusions was studied also using outbred rabbits. In this present study, we demonstrate that the tumor growth promoting effect of allogeneic blood transfusions is mediated by donor leukocytes and that this effect can be abolished by their removal before transfusion. We show also that the allogeneic blood transfusion tumor growth-promoting effect can be passively transferred to naive animals (both mice and rabbits) using spleen cells from allogeneically transfused animals. In these experiments, numbers of metastatic pulmonary nodules were significantly increased in both mice and rabbits that had received spleen cells from allogeneically transfused animals compared with those that had received spleen cells from syngeneically transfused animals, or from animals that had been transfused with leukodepleted allogeneic blood. PMID- 8461474 TI - Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia. AB - Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men. PMID- 8461475 TI - Long-term follow-up of a phase III study of recombinant human granulocyte macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies. AB - One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long term safety of recombinant human granulocyte macrophage-colony-stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF. PMID- 8461476 TI - The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease following unrelated donor marrow transplantation. AB - The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease (GVHD) following unrelated donor (URD) marrow transplantation is unknown. We studied 129 patients who underwent marrow transplantation from HLA-A, -B, DRB, and -DQB matched URDs to determine whether matching for HLA-DPB1 alleles significantly decreased the risk of developing acute GVHD. HLA-DPB1 alleles were determined by sequence-specific oligonucleotide hybridization and by the number of patient DPB1 alleles not shared by the donor scored. The Kaplan-Meier probability of developing grades II to IV acute GVHD was determined for patients incompatible for zero (group A), one (group B), or two (group C) DPB1 alleles. Of the 129 pairs, there was no recipient DPB1 incompatibility in 28 (22%), one DPB1 mismatch in 72 (56%), and two DPB1 mismatches in 29 (22%). The probability of grades II to IV acute GVHD was 0.69 (0.50, 0.86) for group A, 0.83 (0.73, 0.91) for group B, and 0.72 (0.56, 0.87) for group C (P = .63). These results indicate that matching patients and unrelated donors for HLA-A, -B, -DRB, and -DQB does not predict for matching at DPB1. However, recipient incompatibility for DPB1 alleles does not detectably influence the risk of acute GVHD. Therefore, HLA-DP disparity should not be used as an exclusion criterion for donor selection in unrelated marrow transplantation. PMID- 8461477 TI - Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery. AB - Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1 pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment. PMID- 8461478 TI - Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program. AB - More than 410,000 people participated in the National Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 volunteers had donated marrow. While the incidence of serious morbidity as a result of bone marrow donation is rare, the incidence of lesser complications and the long-term consequences of marrow donation are not known. To determine the incidence of donor complications and measure the recovery time of volunteer, unrelated marrow donors, we analyzed the results of surveys of the first 493 persons who donated marrow through the NMDP. The marrows were collected at 42 centers. The median age of the donors was 37.9 years (range 19.1 to 55.6 years). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL). Autologous red blood cells were transfused to 89.8% (439) of donors but only 0.6% (3) of donors received allogeneic blood. Acute complications related to the collection procedure occurred in 5.9% of donors; but a serious complication, apnea during anesthesia, occurred in only one donor. When donors were questioned approximately 2 days following discharge from their hospitalization, most donors described symptoms related to the collection; 74.8% experienced tiredness, 67.8% experienced pain at the marrow collection site, and 51.6% of the donors experienced low back pain. Donors were surveyed repeatedly until they felt that they had recovered completely. Mean recovery time was 15.8 days; however, 42 (10%) donors felt that it took them > or = 30 days to recover fully. The duration of the marrow collection procedure and duration of anesthesia both positively correlated with donor pain and/or fatigue following the collection; but the duration of the collection procedure had the highest correlation with post-collection pain and fatigue. The volume of marrow collected per unit of donor weight was more weakly correlated with donor pain and/or fatigue than the anesthesia and collection times. When multivariate analysis was used to analyze the correlation between donor recovery time and these variables, only the duration of the collection was found to correlate significantly with donor recovery time (P = .001). This analysis demonstrates that marrow donation is well tolerated with few complications. To decrease further the incidence of donor discomfort and recovery time following donation, the duration of the collection procedure, and probably the duration of anesthesia, and the volume of marrow collected, should be kept to a minimum. PMID- 8461479 TI - Psychosocial effects of unrelated bone marrow donation: experiences of the National Marrow Donor Program. AB - In this study, we investigated the psychosocial effects of unrelated marrow donation. Survey questionnaires were administered pre-donation, shortly post donation, and 1 year post-donation to all donors through the National Marrow Donor Program over a 3-year period. Univariate, bivariate, and multivariate analyses were then performed. Donors were generally quite positive about the donation 1 year post-donation: 87% felt it was "very worthwhile" and 91% would be willing to donate again in the future. Marrow donors were more likely than kidney donors to feel better about themselves as a result of the donation (P < .001). Donors with longer collection times, in general, had less positive psychosocial outcomes from the donation. Donors who experienced lower back pain or difficulty walking as a result of the donation were more likely to experience the donation as more stressful and painful than expected, but no more likely to experience it as less positive emotionally than donors who did not experience these side effects. PMID- 8461480 TI - Autologous bone marrow transplantation for non-Hodgkin's lymphoma in first remission. PMID- 8461481 TI - Selection of patients with aggressive lymphoma in remission candidates to autologous bone marrow transplantation. PMID- 8461482 TI - Oral iron chelator L1 and autoimmunity. PMID- 8461483 TI - The repeated sequence (AT)x(T)y upstream to the beta-globin gene is a simple polymorphism. PMID- 8461484 TI - Immunophenotypic features of t(8;21) (q22;q22) acute myeloid leukemia in adults. PMID- 8461485 TI - Interleukin-3 enhances the endogenous leukotriene production. PMID- 8461486 TI - Chronic stress from the Goiania 137Cs radiation accident. AB - At the invitation of the Brazilian government, the authors conducted a multidisciplinary field study in Goiania, Brazil, 3 1/2 years after an accident involving 137Cs, a radioactive cesium isotope. They compared subjects exposed to low levels of ionizing radiation, subjects who experienced anticipatory stress from fear of radiation exposure, and a nonirradiated control group. Results indicated the presence of chronic stress, as measured by psychological, behavioral, and neuroendocrine indices, in subjects who were exposed as well as in subjects fearful of potential radiation exposure. Anticipatory stress associated with potential exposure to ionizing radiation resulted in a level of stress similar to that from actual exposure to ionizing radiation. These findings have implications for past and future radiation accidents. PMID- 8461487 TI - Coping with recent life events: the interplay of personal and collective resources. AB - The importance of personal and collective resources in coping with recent life events was studied among 230 kibbutz members. The sense of coherence, a global life orientation that detects the ability to avoid stressors and to choose appropriate coping strategies and resources, represented personal resources. Collective resources, embedded in the social system to which one belongs, were measured by membership in a religious kibbutz, the kibbutz being viewed as a powerful, collective-coping resource by itself. Physical well-being, psychological distress, and functional limitations were used as outcome measures. Both types of resources have a salutogenic effect, but sense of coherence appears to be a better resource for avoiding the effect of recent life events and for moderating psychological distress and functional limitation after experiencing such events. The two types of resources have no additive effect, nor do they compensate for each other. Only one significant interaction was found, suggesting that the combination of the two resources is useful in avoiding functional limitation. It is also suggested that collective resources have a slight positive effect on personal resources, which, in turn, take over and become most valuable in coping with recent life events. When stress affects social functioning, these same personal resources facilitate the mobilization of whatever collective resources are available. PMID- 8461488 TI - The effect of psychiatric disorders on weight loss in obesity clinic patients. AB - Research on psychiatric disorders in obesity has indicated that obese people are not psychiatrically different from nonobese people. Few studies, however, have addressed the potential impact of psychopathology on weight control. In the present study, a consecutive sample of 37 patients presenting to a major metropolitan weight control unit were given structured diagnostic interviews (Structured Clinical Interviews for Diagnosis I and II). These patients completed one of two 12-week diet programs involving either behavior modification or liquid protein diets. After 12 weeks of a liquid protein formula diet, patients with no personality disorder lost significantly more weight than personality disordered patients; personality disordered patients on a behavioral diet tended (p < .15) to lose more weight during a 12-week diet than the patients without personality disorders. These data suggest that there are differential responses to liquid protein and behavioral diets, depending on the presence or absence of a personality disorder. PMID- 8461489 TI - Medical students' differential use of coping strategies as a function of stressor type, year of training, and gender. AB - The cognitive-transactional model of stress was used to study the process by which medical students cope with stress. The study examined the coping responses employed by male and female first- and fourth-year medical students as a function of those situations they appraised as most stressful. Multivariate analyses of variance (MANOVAs) revealed that preferred coping strategies varied by stressor type and year of training. In dealing with medical-school-related stressors, first-year students used self-blame and problem-solving styles of coping more than did fourth-year students. When dealing with interpersonal stressors, however, fourth-year students tended to use confrontive coping more than did first-year students. Surprisingly, whether the student was a man or a woman had no impact on coping responses. The findings underscored the importance of the moderating impact of the appraisal process on the coping strategies employed to manage stressful situations. Implications for medical education, as well as for future research on coping with stress, are discussed. PMID- 8461490 TI - The effects of task demand and decision latitude on cardiovascular reactivity to stress. AB - This study investigated the effects of task demand (absence or presence of time pressure) and decision latitude (choice or no choice over a task) on cardiovascular and affective responses to stressful tasks among 70 college students. Subjects also rated whether they felt under pressure and the extent to which they felt in control. Time pressure was related to elevated systolic blood pressure (SBP) responses among men and increased negative affect for both sexes. Lack of choice over the task also resulted in increased negative affect in both sexes. The least stressful condition--having a choice in the absence of time pressure--resulted in reduced negative affect. In addition to the effects of manipulated decision latitude and demand, perceptions of being in control were associated with reduced SBP among women who had a choice. Perceived control also contributed to reduced negative affect among men. These results suggest that the postulated negative effects of high demand and low decision latitude (ie, job strain) on cardiovascular health may be mediated in part by increased cardiovascular reactivity and negative affect. PMID- 8461491 TI - The challenge of calcific aortitis. AB - Coronary bypass and valvular operations have become more prevalent as the nation's elderly population grew 21% within the last decade. Ascending aortic calcification was a manifestation of this aging process. Aortic cannulation appeared impossible. Postoperatively, the stroke rate reached 14%, and the number of unexpected deaths rose sharply. Embolization of calcific and arteriosclerotic debris to cerebral and coronary vessels is believed to be the cause. The sharp, beveled, and narrowed jet-forming tips assaulted the delicate and soft intima of the artery. Nineteen cases of severely calcified aorta with increased predictable risk factors were operated on within the past 5 years. There were 12 coronary bypass grafts, 4 ventricular aneurysmectomies, and 3 valve replacements. Five of these cases were redo operations. The average age for these patients was 73.7 years. With the availability of the cannula introducer, we were able to find a small soft spot inside the arch or ascending aorta and cannulate these patients. We began to cool the patients down immediately and chose one of the three available methods for cardiac arrest. By changing the angle of application and direction of the axis of the clamp, we could cross-clamp the aorta loosely in 11 patients and administer cardioplegia. Intraluminal balloon occlusion of the ascending aorta was used once. The remainder of the cases had fibrillatory arrest. All proximal anastomoses in the coronary patients were done while on cross-clamp, intraluminal balloon occlusion, or brief periods of circulatory arrest. All sutures were passed from inside the aorta to avoid displacing or dissecting calcified plaques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461492 TI - Surgical treatment of Wolff-Parkinson-White syndrome: epicardial approach without the use of cardiopulmonary bypass. AB - Epicardial dissection without the use of cardiopulmonary bypass (CPB) was performed in 88 patients (56 males and 32 females, mean age 31.9 years). With intraoperative epicardial mapping, 101 accessory pathways were detected, with multiple pathways in 11 patients. CPB was avoided in all but one patient due to frequent onset of atrial fibrillation with rapid ventricular rate. Surgical ablation was successful in 86 patients (97.6%). Three patients required multiple surgical procedures because of persistence of conduction along a component of the original pathway. All but two patients were discharged without antiarrhythmic medication; these two patients were given quinidine therapy because of atrial fibrillation, but had normal early and late electrophysiological studies. Surgical ablation of Kent bundles by the epicardial approach for the treatment of Wolff-Parkinson-White syndrome can be achieved without the use of CPB. Optimal and steady exposure of the area are mandatory for the procedure, and dissection is eased by avoidance of heparin required for CPB. PMID- 8461493 TI - Mitral valve replacement in the presence of severe valvular and annular calcification. AB - Degenerative and rheumatic mitral valve disease are associated with calcification of the annulus, leaflets, and subvalvular mechanism. Surgical treatment is greatly affected by the presence of such calcification, which frequently precludes successful repair, mandating valve replacement. Dense calcification of the posterior leaflet, annulus, and chordae can cause great difficulty in the insertion of a prosthetic device, and is associated with a high frequency of technical complications. We have devised a technique of replacing the mitral valve in the face of such severe calcification, which allows the surgeon to safely insert a single disc mechanical prosthetic valve, avoiding the calcification completely. A large Teflon felt collar precludes the need to place any sutures through the posterior valve leaflet. Successful early experience with five patients, exhibiting both degenerative and rheumatic disease, is described. PMID- 8461494 TI - Intra-arterial aortoinfundibuloplasty: hemodynamic and anatomical study of a new method for the enlargement of a small aortic annulus. AB - A new method for prosthetic valve replacement in a small aortic annulus is described. An anatomical examination showed that the intra-arterial approach via the main pulmonary artery made it feasible to incise the aortopulmonary septum at the middle point of both coronary ostia and also to relieve left ventricular outflow tract obstruction with a two-dimensional patch. The pressure study in three mongrel dogs demonstrated that 6-mm augmentation of the host aortic annulus with this procedure made no significant difference in the pressure gradient between the right ventricle and the main pulmonary artery before and after operation. The right ventricular end-diastolic pressure did not show any significant change with respect to hemodynamics. It is expected from these results that our procedure could be used for the treatment of various types of left ventricular outflow tract stenosis without affecting the hemodynamics and, especially, right ventricular function. PMID- 8461495 TI - The surgical anatomy of ventricular septal defects associated with overriding valvar orifices. AB - This is the second review in a three-part series concerned with the description and categorization of ventricular septal defects. By viewing the defects from the right ventricular aspect, they can be placed into one of three classes: perimembranous, muscular, or doubly committed and juxta-arterial. According to the posteroinferior margin of the third group, these could extend to become perimembranous or muscular. In this review, the complications produced by malalignment of the septal structures associated with overriding of an arterial or atrioventricular valve are described in detail. It shows that although there are problems in defining the extent of any interventricular communication, these ventricular septal defects can be classified with the same categorization as developed for those not associated with overriding. The nosology developed is able to serve as a guide to the surgeon to the site of the specialized axis for atrioventricular conduction. PMID- 8461496 TI - Resection of infected ventricular aneurysm (Salmonella) following septic saddle embolus. AB - Bacterial infection (Salmonella enteritidis) of left ventricular true and false aneurysm in a 62-year-old man was followed by septic saddle embolus. The septic saddle embolus was removed and the aneurysm was later resected with coronary bypass grafting. The patient is alive with satisfactory function over 5 years postoperatively. PMID- 8461497 TI - Management of absent pulmonary valve syndrome with patent ductus arteriosus. AB - The etiology of absent pulmonary valve syndrome is unknown. Several theories have been advanced to explain the associated findings of a rudimentary pulmonary valve, ventricular septal defect, aneurysmal pulmonary arteries, and absence of the ductus arteriosus. The patient presented here would contradict these currently held theories. A review of the literature follows the case report. PMID- 8461498 TI - Electrophysiological consequences of hypothermic hyperkalemic elective cardiac arrest. AB - While the development of pharmacological cardioplegic solutions for myocardial protection during cardiopulmonary bypass (CPB) have significantly lengthened the safe operating time for cardiac surgical procedures, the introduction of hypothermic hyperkalemic cardioplegia (CPG) has markedly increased the incidence of postoperative arrhythmias and conduction abnormalities. Using a customized modification of a computerized mapping system, we have developed a large animal porcine model of CPB that is exquisitely sensitive to the electrophysiological (EP) derangements imposed by ischemia and cardiac arrest. This model is able to measure spatial and temporal parameters of ventricular activation with high resolution, using an array of up to 84 epicardial electrodes that can be reproducibly placed on the surface of the heart utilizing known epicardial anatomical markers (e.g., coronary arteries). With this system we have measured the spectrum of clinically observed EP disturbances caused by CPG, from slowed intraventricular conduction to complete heart block. Compared to the control group of hypothermia alone, 2 hours of crystalloid CPG arrest had a significant slowing effect on ventricular activation (p < 0.05). CPG was accompanied, in each animal, by profound changes in the spatial distribution of ventricular activation and persistent slowing of ventricular activation. Traditional EP parameters of effective refractory period and pacing threshold were unchanged by CPG. Smaller temporal and spatial changes were observed in the control group, but were always reversed by 90 minutes of warm reperfusion. We conclude that CPG induces injury of the specialized conducting system and, to a lesser degree, the myocardium. This model will afford us the opportunity to test new methods of CPG to further improve myocardial preservation during CPB. PMID- 8461499 TI - Warm heart surgery: concept, concerns, and future course. AB - Hypothermia has been considered a prerequisite for decreasing oxygen consumption and providing myocardial protection. The decrease in myocardial oxygen consumption however, is more closely related to the state of electromechanical arrest than to hypothermia. The rationale for warm blood cardioplegia is based not only on electromechanical quiescence but equally on facilitation of O2 delivery. This report outlines the basis for the concepts, the various concerns and the possible future directions of warm blood cardioplegia. PMID- 8461500 TI - Myocardial antioxidant defenses during cardiopulmonary bypass. AB - In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass. PMID- 8461501 TI - Optimal electrical stimulation for latissimus dorsi muscle after cardiomyoplasty. AB - The aim of this study was to evaluate the functional state of latissimus dorsi muscle (LDM) during electrical stimulation following cardiomyoplasty. Both single pulses and bursts of impulses were used for electrical stimulation. In 15 dogs, studies were carried out for 2 months, while in 19 patients, the follow-up period after cardiomyoplasty was 10 +/- 3.1 months. The LDM was punctured by needle electrodes at various intervals following cardiomyoplasty, and the changes of the rheomyosignal (RMS) curve were registered on the "Reostim-06." During the follow up study, it was found that: (1) signal amplitude decreased 30%; (2) the contraction duration of LDM increased 38%; (3) the contraction velocity decreased 43%; and (4) relaxation velocity decreased 61%. There is a correlation between LDM mechanical contractile force and RMS indices (r = 0.8). The RMS index was a function of the electrical burst duration and the number of impulses in the bursts. Thus, RMS parameters can characterize the functional state of LDM, and they may be used in designing a new generation of electromyostimulators for optimal LDM stimulation at different periods after cardiomyoplasty. PMID- 8461502 TI - Dynamic cardiomyoplasty as an effective therapy for dilated cardiomyopathy. AB - Nine male patients with dilated cardiomyopathy unresponsive to maximal medical therapy were submitted to dynamic cardiomyoplasty according to the technique described by Carpentier and Chachques, and preliminary postoperative results are reported. Seven patients were in New York Heart Association (NYHA) Class III and two were in intermittent Class IV. The mean age was 56 years (range 51 to 61 years). Preoperative ejection fraction (EF) by multiple gated acquisition ranged from 14% to 28% (mean 20.7%). No additional surgery was performed. Transesophageal echocardiographic monitoring was used during surgery to guide the wrapping procedure. There was no operative mortality. There was one early death (1 month). One late death (sudden death) occurred 7 months after surgery despite significant clinical improvement. Follow-up ranges from 2 to 16 months. Six patients were submitted to hemodynamic evaluation from 4 to 6 months after surgery by transthoracic and transesophageal echo-Doppler assessment. Effective latissimus dorsi support was clearly documented in all patients by comparing postoperative basal hemodynamic values (Cardiomyostimulator [Medtronic, Inc.] switched off) and data obtained during assisted beats (EF increased from 19.4% +/ 8.6% to 32.6% +/- 13.8%, p = 0.043; and stroke volume increased from 51.6 +/- 20.6 mL to 63.0 +/- 22.0 mL, p = 0.014). All patients who completed the latissimus dorsi training protocol were in NYHA Class I or II. A significant reduction in postoperative medical therapy was achieved in all patients. Our preliminary results confirm that the cardiomyoplasty procedure is to be considered a safe and valuable mean for treating selected patients with dilated cardiomyopathy refractory to maximal pharmacological treatment. PMID- 8461503 TI - Skeletal muscle ventricles with efferent valved homograft. AB - Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in seven beagles. Following 3 weeks of vascular delay and 6 weeks of electrical conditioning, the SMVs were connected in series with the thoracic aorta using a valved aortic homograft for the efferent limb. The SMVs were stimulated to contract synchronously during diastole. Effective aortic diastolic counterpulsation was achieved in all dogs, with an average 24.2% +/- 15.3% improvement in diastolic pressure. In two animals surviving beyond 3 months, increase in SMV function was noted over time. Appropriate aortic homograft valve function was documented by echocardiogram. Acute reversible heart failure was induced with propranolol in one dog alive after 126 days. A 61.3% reduction in cardiac output and a 37.6% reduction in mean arterial blood pressure were achieved. During profound low cardiac output, SMV stimulation with 33 Hz and 50 Hz improved cardiac output by 16.9% and 17.8%, improved the tension time index by 14.9% and 16.1%, and improved the endocardial viability ratio by 34.1% and 34.1%, respectively. These results again demonstrate the long-term effectiveness of SMVs as aortic counterpulsators. A valve in the efferent limb of the SMV system functions appropriately over time and may improve the efficiency of the system. PMID- 8461504 TI - Myocardial stunning: an overview. AB - Over the past two decades, we have challenged the belief that transient ischemia is benign with little functional sequelae following resolution of ischemia. The phenomenon of prolonged postischemic contractile dysfunction, or of myocardial stunning, has been developed and is under investigation using multiple experimental and clinical models. Classifications of myocardial stunning have been suggested and include single and multiple reversible ischemic episodes, partially reversible episodes, and global ischemia. More challenging is the understanding of the mechanisms of myocardial stunning, including free radical protection, excitation-contraction uncoupling, altered calcium flux, microvascular dysfunction, and impaired energy production and use. Finally, advances have been made in the clinical arena, including development of new more sensitive technologies to detect dysfunction, and development of potentially important therapies, including free radical scavengers, adenosine-regulating agents, and calcium channel blockers. In this brief overview, we focus on myocardial stunning, including a historical perspective of coronary occlusion, and definition, classification, and clinical implications of myocardial stunning. PMID- 8461505 TI - Protean causes of myocardial stunning in infants and adults. AB - Myocardial stunning can follow regional or global ischemia in the adult or immature heart. This report reviews some of our studies of the protean causes of stunning including energy and substrate depletion, inefficient oxygen utilization, calcium loading, acidosis, oxyradical damage, and summarizes studies and strategies to limit its occurrence. Data showing that reintroduction of molecular oxygen during reoxygenation of immature cyanotic hearts can cause stunning via a newly described biochemical pathway involving superoxide anion and nitric oxide are also included. PMID- 8461506 TI - Clinical evidence of myocardial stunning in patients undergoing CABG surgery. AB - Although patients who have undergone coronary artery bypass graft (CABG) surgery frequently present with symptoms suggesting that myocardial stunning has occurred, measurements of regional myocardial function and perfusion are difficult in clinical settings. Several studies have used left ventricular function indices (i.e., cardiac index, left ventricular stroke work index, ejection fraction) to assess myocardial stunning immediately following CABG surgery. These changes in ventricular function have been found to be reversible and the clinical data are consistent with the occurrence of myocardial stunning. Myocardial metabolism is also reportedly depressed following CABG surgery. Decreases in myocardial oxygen extraction, consumption, and lactate utilization all point to the presence of myocardial stunning, as do abnormalities in regional wall-motion and electrocardiographic changes (i.e., transient Q waves) described in patients who have undergone CABG surgery. New approaches to differentiating viable from nonviable myocardial tissue will likely include stress echocardiography using new stress agents, ultrasound contrast agents, and high frequency ultrasound. PMID- 8461507 TI - Identifying stunned myocardium during cardiac surgery: the role of myocardial contrast echocardiography. AB - Differentiation of reversibly stunned myocardium from irreversibly damaged (infarcted) myocardium is critically important in patient management. Current methods for monitoring myocardial function yield only nonspecific assessments of myocardial viability. On the other hand, myocardial contrast echocardiography (MCE) can be used to evaluate the extent of myocardial perfusion as well as the efficacy of myocardial protection in patients undergoing coronary artery bypass graft (CABG). This system includes an external ultrasound unit and an internal tracer, usually gaseous microbubbles, which reflect the ultrasonic beam. Previous studies have shown that myocardial risk areas identified with MCE correlate with areas defined by technetium autoradiography and infarction size. We have used MCE to evaluate coronary artery bypass patients (N = 21) with regard to myocardial function and cardioplegia perfusion patterns. A significant correlation (p < 0.01) was found between abnormal contrast enhanced cardioplegia patterns and depression of left ventricular function. Refinements to ultrasound technology and contrast agents will further enhance the diagnostic power of MCE for the quantification of myocardial blood flow. PMID- 8461508 TI - The effect of prophylactic nitroglycerin infusion on the incidence of regional wall-motion abnormalities and ST segment changes in patients undergoing coronary artery bypass surgery. AB - The effects of nitroglycerin (NTG) on regional wall-motion abnormalities, ST segment changes, and the incidence of myocardial infarction (MI), cardiac failure, and mortality were studied in 30 patients undergoing coronary artery bypass. Patients received continuous infusions of either normal saline or NTG (1 microgram/kg per min [low dose] or 2 micrograms/kg per min [high dose]) beginning at anesthesia and continuing for 4 hours postoperatively. The occurrence of wall motion abnormalities as detected by transesophageal echocardiography was 38 events in the normal saline group (N = 10). Significantly fewer events (p < 0.05) were recorded in the low dose and high dose NTG groups (20 events and 15 events, respectively) compared to controls. There were no significant differences between the control and NTG groups with regard to the incidence of Holter ST segment events or the incidence of MI, cardiac failure, or cardiac death. NTG reduced the incidence of echocardiographic wall-motion abnormalities in a dose dependent manner while having no significant effect on other parameters examined. PMID- 8461509 TI - Clinical markers and clinical consequences of stunned myocardium. AB - Clinical markers must be identified to distinguish between stunned and acutely ischemic myocardial tissue, as well as to assess the viability of myocardium. Evaluation of electrocardiographic ST segment abnormalities can distinguish transmural oxygen deprivation from subendocardial oxygen declines, but stunned myocardium may have normal ST segments. Myocardial contrast echocardiography can estimate regional myocardial blood flow but ultrasound measurement of blood flow is not always able to discern stunned from nonviable myocardium. Change in extracellular pH has been used to study ischemia, but has not yet been shown to reflect differences between stunned and ischemic myocardium. A combination of clinical markers of flow, delivery, and oxygen consumption may be necessary in order to differentiate between stunned and ischemic regions. This distinction can have important therapeutic consequences because patients with acutely ischemic but viable myocardium may be ultimately harmed by inotropic drugs that increase myocardial oxygen demand. In contrast, inotropes may be indicated for stunned myocardial tissue. The determination of the reversibility of myocardial dysfunction can also impact on decisions to use mechanical cardiocirculatory support. Differentiation of stunned and ischemic myocardium might also streamline ICU assignments and lead to more effective use of high technology resources. PMID- 8461510 TI - Is post cardiopulmonary bypass dysfunction a special form of stunning? AB - It has been suggested that cardioplegic arrest during cardiopulmonary bypass (CPB) produces global myocardial ischemia with a risk of myocardial stunning. It has also been postulated that anesthetic technique may affect the course of post CPB myocardial stunning via exaggerated myocardial depression. However, we have previously found that global ventricular and regional myocardial responses to halothane do not differ in post-CPB and pre-CPB dogs. Our examination of the effects of CPB on the beta-adrenergic function revealed that beta-adrenergic receptor function is only slightly decreased immediately following (i.e., 1 min) and 30 minutes post-CPB. A dose-response relationship was established for dobutamine, with decreased responsiveness noted at both times. Since other data show normal inotropic stimulation of stunned myocardium, decreases in dobutamine responsiveness cannot be explained by beta-receptor desensitization. Overall, these data indicate that CPB does not result in myocardial stunning. The differences between these data and others showing myocardial stunning following CPB may be due to several factors, such as anesthetic regimen, lack of coronary blood flow abnormalities, and a reduction in sarcoplasmic reticular damage due to the hypothermic conditions used. PMID- 8461511 TI - Can myocardial stunning contribute to myocardial infarction during coronary artery bypass surgery? AB - Myocardial stunning commonly occurs after cardiopulmonary bypass (CPB). Myocardial stunning can be cardioprotective under some conditions, but in other situations may actually contribute to myocardial infarction (MI). Vascular endothelial stunning may be one of the mechanisms by which myocardial stunning can cause MI. It has been found that 15 minutes of reversible ischemia is enough to cause elevations in vascular resistance and impairment of vasodilator responsiveness. However, no correlation between contractile dysfunction and microvascular stunning has been observed. Transduction defects (increased oxygen extraction and consumption despite normal regional oxygen blood flow and delivery) may be another mechanism by which stunning predisposes to MI, indicating uncoupling of substrate utilization from energy production. In addition, abnormalities in wall motion, oxygen free radical toxicity, hypotension, use of inotropic agents (leading to increased oxygen consumption, high heart rates, and arrhythmias) increase the risk of cellular necrosis. Following CPB, flow limitations due to diffuse atherosclerosis in some areas may result in poor contractility, and newly grafted areas have a high probability of becoming ischemic and stunned. These areas are likely to contribute to MI. PMID- 8461512 TI - Myocardial stunning after coronary bypass surgery. AB - At the Toronto Hospital, 2,510 patients received isolated coronary bypass grafts (CABG). Overall mortality was 2.3%, the incidence of low output syndrome (as defined by need for inotropic agents or intraaortic balloon pump) was 9.2%, and mortality among low output syndrome patients was 16%. We have attempted to identify factors that minimize cardiac injury. We have previously shown that free radical injury occurs during CABG: coronary blood contains increased levels of conjugated dienes after cross-clamp release; and, there is a reduction in the antioxidant, alpha-tocopherol. In vitro studies revealed that ascorbic acid and alpha-tocopherol protect cardiac myocytes, while endothelial cells are protected from free radical injury by superoxide dismutase and catalase. To test the former two antioxidants in vivo, we used left anterior descending artery (LAD) occlusion in the dog followed by 2 to 4 hours of reperfusion. When administered in deoxygenated saline at 30 seconds prior to reperfusion and 4 minutes after release of LAD occlusion, both agents significantly reduced the infarction area compared to simple reperfusion or deoxygenated saline alone. Antioxidants therefore have the potential to reduce the ischemic injury and myocardial stunning that accompany CABG. PMID- 8461513 TI - Does ventricular fibrillation cause myocardial stunning during defibrillator implantation? AB - Induction of ventricular fibrillation (VF) is an important part of the process of inserting implantable cardioverter defibrillators (ICDs), allowing the measurement of defibrillation thresholds. However, animal studies have revealed that repeated cycles of VF and defibrillation result in depressed left ventricular (LV) function and reduced cardiac output. Short intervals of VF do not affect myocardial contractility but longer periods produce heart failure. Induced VF was used in a canine model to study profound myocardial stunning leading to heart failure, as well as the therapeutic potential of the phosphodiesterase inhibitor, amrinone (combined with epinephrine and norepinephrine). Amrinone was found to significantly (p < 0.05) increase contractility when added to a stable preparation supported by epinephrine and norepinephrine infusion; amrinone or catecholamines alone had no effect. In the clinical setting, the following factors may affect LV contractility during ICD surgery: catecholamines released as a result of hypotension; negative VF; ischemia; antiarrhythmic drugs; anesthetics; and bradycardia after device testing. Patients (n = 125) have tolerated ICD insertion well. Early data reveals no significant changes in ejection fraction. Though rare, death due to myocardial stunning and LV power failure can occur during ICD insertion. It may be possible to use arterial pressure monitoring to predict this event in vulnerable patients. PMID- 8461514 TI - Myocardial stunning and preconditioning: age, species, and model related differences: role of AMP-5'-nucleotidase in myocardial injury and protection. AB - Mechanisms of myocardial stunning include myocardial adenosine triphosphate (ATP) depletion, catecholamine release, and oxygen free radical formation. Although the latter is the most widely supported mechanism, levels of 5'-nucleotidase (directs AMP dephosphorylation) are inversely related to functional recovery following ischemia and may also have a role in ischemic injury. Previous studies reveal that 5'-nucleotidase levels increase with age and also vary with species. An inhibitor of this enzyme (alpha, beta methylene adenosine 5'-diphosphate) was effective in maintaining AMP levels in vitro but was ineffective in dogs due to limited permeability. Observed species-specific differences in recovery from myocardial stunning may be related to differences in AMP accumulation and subsequent metabolism. Species showing improved recovery from stunning may accumulate AMP as a result of feedback inhibition of 5'-nucleotidase. Using a model of extreme experimentally-induced ischemia, we found that adenosine treatment allowed full recovery of ventricular function within 30 minutes, probably by entrapping ATP catabolites. Similarly, enhancement of adenosine production by N-diarylalkylpeprazine derivatives has also been shown to be cardioprotective in the setting of global normothermic ischemia. Novel strategies for pharmacological intervention in the ATP catabolic pathway should use animal models involving species that are tolerant to myocardial stunning. PMID- 8461515 TI - Metabolic correlates of myocardial stunning and the effect of cardiopulmonary bypass. AB - In order to study the metabolic consequences of myocardial stunning, repeated coronary occlusions were performed in dogs. The production of CO2, adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) by myocardial cells was assessed, along with extracellular and intracellular pH. Our results indicate that regional coronary artery occlusion reduces the ability of the myocardium to produce H+ and CO2 and to replenish ATP post ischemia. These alterations, then, represent the hallmark of metabolic viability during periods of ischemic insult. Decreases in PCr and Pi were completely eliminated during reperfusion and, therefore, are ot reflective of myocardial stunning. When normothermic cardiopulmonary bypass (CPB) is instituted and the coronary artery is occluded three times with reperfusion between each occlusion, alterations in myocardial H+ and high energy phosphates are identical to those observed using only repetitive coronary occlusion. Systemic hypothermia during CPB does not protect against myocardial stunning; however, it is anticipated that interventions that prevent the reduction in H+ and ATP levels may overcome the effects of myocardial stunning that occur during cardiac surgery. PMID- 8461516 TI - Reversible postischemic ventricular dysfunction: biochemical insights. AB - Myocardial stunning, or reversible postischemic ventricular dysfunction, occurs clinically much more frequently than was originally assumed when this phenomenon was first described in experimental studies. Despite the fact that stunned myocardium may appear histologically normal and have a normal metabolic profile, ventricular contractility is severely impaired. In a number of studies using both global and regional stunning models, we have demonstrated impaired oxygen extraction and abnormal patterns of oxygen consumption. In addition, impaired calcium transport or uptake by the sarcoplasmic reticulum occurs and there is sarcolemmal disruption during stunning despite reversibility of the ischemic injury. Although oxygen free radical production is thought to occur only early during postischemic reflow, the use of oxygen radical scavengers in a model of regional stunning was shown to attenuate the ventricular dysfunction. PMID- 8461517 TI - Relationship of severity of myocardial stunning to ATP dependent potassium channel modulation. AB - Pharmacological modulation of ATP sensitive potassium channels (K+ATP channels) in vivo may influence ischemia and reperfusion injury of myocardium. The purpose of this investigation was to ascertain the actions of multiple K+ATP channel openers and interactions with a K+ATP channel antagonist in a model of stunned myocardium in anesthetized and conscious dogs. The results indicate that the K+ATP channel openers, aprikalim and nicorandil, enhance recovery of regional contractile function of stunned myocardium. This action was blocked by the selective K+ATP antagonist, glyburide. The beneficial effects of K+ATP channel openers were not related to changes in systemic hemodynamics or coronary collateral perfusion, but instead may be a manifestation of direct cardioprotective actions of these compounds. PMID- 8461518 TI - Cellular and subcellular aspects of myocardial stunning. AB - Possible mechanisms of myocardial stunning at the cellular level include oxygen free radical production, neutrophil-induced damage, accelerated degradation of adenosine triphosphate (ATP), ischemia-induced myofibrillar damage, and calcium overload due to abnormal sodium/calcium exchange. Although the role of free radicals is generally accepted, their source(s) and clinical importance remain controversial. Similarly, an association of a declining ATP pool with myocardial stunning is well established but may not have clinical relevance as treatments that result in functional recovery do not always increase ATP levels. Little evidence exists for a strong link between myofibril damage and myocardial stunning. In contrast to these mechanisms, altered calcium homeostasis is an attractive hypothesis because: normal hearts perfused with high levels of calcium develop contractile dysfunctions similar to stunning; stunned hearts perfused with low calcium have increased function; calcium overload inhibition attenuates stunning; and reduced calcium ATPase activities have been found in sarcoplasmic reticulum from stunned hearts. Future research efforts should strive to simultaneously evaluate flow, function, and metabolic changes that occur in the stunned heart. Changes in the latter may eventually be studied using the techniques of molecular biology, integrating knowledge at the molecular level with clinical needs. PMID- 8461519 TI - Models of myocardial stunning. AB - The use of animal models is a valuable approach to the elucidation of the pathophysiology of myocardial stunning. Coronary occlusion followed by reperfusion produces stunning experimentally, mimicking a myocardial infarction followed by thrombolysis, angioplasty, or coronary bypass. Timing of occlusion and duration to avoid necrosis is critically dependent on the animal species used. For example, 10 minutes of occlusion is required in pigs, 20 minutes in canine models, and sheep or rabbits may require ischemic times somewhere in between. Alternatively, two to six cycles of occlusion followed by reperfusion (repetitive occlusion) may be used. In addition, global ischemia with the heart vented and on cardiopulmonary bypass may simulate myocardial stunning. In this case, 30 minutes produces 50% reductions in myocardial contractility in dogs while 10 minutes is needed in pigs. Animal models have also included the study of a stunned heart in an in vitro apparatus. In these models, discontinuation of perfusion for 10 to 15 minutes is needed to produce stunning in rats, 20 minutes in rabbits, and probably longer periods in dogs and pigs. Myocyte cell cultures may also be valuable for studying responses to ischemia and reperfusion at the cellular level. It is generally agreed that cardioplegic protection, antioxidants, metabolic enhancements, and blockade of calcium overload are some of the strategies that can minimize or eliminate myocardial stunning. PMID- 8461520 TI - Coronary pressure-flow regulation in the stunned myocardium. AB - In this study, we used a swine model to study coronary autoregulation in the stunned myocardium. In 18 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery controlled via an extracorporeal perfusion circuit. Stunning was induced by reducing pump flow to approximately 25% of the baseline value for 15 minutes followed by 1 hour of reperfusion. This ischemia/reperfusion protocol reduced systolic shortening to approximately 50% of control, at 1 hour of reperfusion. Neither the slope of the coronary pressure flow relation (0.41 +/- 0.19 vs 0.48 +/- 0.26 mL/100 g per min per mmHg) nor an autoregulation index (0.43 +/- 0.16 vs 0.30 +/- 0.32) was significantly changed at 1 hour reperfusion (p > 0.05) compared to baseline. These findings argue against the hypothesis that the mechanical dysfunction of the stunned myocardium is due to suboptimal perfusion caused by poor coronary autoregulation. PMID- 8461522 TI - Cytokines and reperfusion injury. AB - Myocardial dysfunction following prolonged ischemia and reperfusion is at least partially dependent upon adhesion of neutrophils to myocardial and endothelial cells. Neutrophils are thought to contribute to reperfusion injury by two mechanisms: impairment of the microvasculature by physical obstruction, and secretion of products that damage microvasculature and myocardium. Cytokines have been shown to play several roles in neutrophil aggregation. Interleukin-6 (IL-6), along with IL-1 and tumor necrosis factor-alpha (TNF-alpha), induces the expression of intracellular adhesion molecule-1 (ICAM-1) in myocytes and endothelial cells, respectively. These cytokines also inhibit contractility and nitric oxide release (a vasodilator), and IL-1 and TNF-alpha have been found to reduce adrenergic stimulation of myocardial contractility by reducing intracellular cyclic AMP levels and uncoupling adenylate cyclase from beta receptors. The transforming growth factors, TGF-alpha and TGF-beta, also have a role in reperfusion injury. TGF-alpha reduces endothelial cell release of nitric oxide, while TGF-beta appears to protect against reperfusion injury by reducing plasma TGF-alpha levels, blocking neutrophil adherence, and promoting nitric oxide release. Although cytokines are likely to have important roles in reperfusion injury, their involvement in myocardial stunning is unclear. PMID- 8461521 TI - Sarcoplasmic reticulum in globally stunned adult and newborn myocardium. AB - Dysfunctional sarcoplasmic reticulum (SR) is thought to be involved in the phenomenon of myocardial stunning. Adult (3 to 4 kg) and neonatal (5 to 7 day old) rabbit hearts were examined for structural SR alterations following ischemic damage and myocardial stunning induced by incubation in Ringer's lactate at 39 degrees C. SR protein yield in neonate hearts (but not adult hearts) significantly decreased (p = 0.01) following 30 minutes of ischemia. In addition, calcium ATPase activity was reduced in both adult p = 0.006) and neonatal (p = 0.02) ischemic hearts. Examination of SR proteins by gel electrophoresis indicated that the levels of several proteins were altered by ischemia. In adult hearts, decreased levels of proteins of 22.5, 31.5, 33, and 83 kilodaltons (kd) were observed. In newborn ischemic hearts, decreases in 29, 37.5, 82, and 83 kd proteins were detected. The quantitative changes in calcium ATPase levels and SR protein content may adversely affect myocardial excitation-contraction coupling and relaxation, contributing to dysfunction in myocardial stunning. PMID- 8461523 TI - Potential role of neutrophil anti-adhesion therapy in myocardial stunning, myocardial infarction, and organ dysfunction after cardiopulmonary bypass. AB - When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil-endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM-1 or ELAM-1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti-neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO2 than controls (N = 3). Antineutrophil therapy may prevent multiorgan system failure in certain high risk patients. PMID- 8461524 TI - Myocardial stunning and reperfusion injury in cardiac surgery. AB - This article reviews the evidence that myocardial stunning during surgical reperfusion after coronary revascularization or heart transplantation is not strictly due to myocardial injury sustained during ischemia, but results from pathophysiological events triggered by reperfusion (reperfusion injury). In sheep, left ventricular (LV) dP/dt and stroke work were reduced up to 50%, and 60% to 70% necrosis was observed in the area at risk during 3 hours reperfusion following coronary occlusion and cardioplegic arrest on bypass. Reperfusion with leukocyte depleted blood, or pharmacological blockade of either thromboxane or leukotriene receptors, provided significant improvements in LV function and myocardial blood flow, with a 40% to 50% reduction in necrosis. Similar results have been obtained using animal heart subjected to 2 to 3 hours arrest at either 4 degrees C or 15 degrees C, simulating cardiac preservation and reperfusion after transplantation. Diastolic pressure was significantly elevated, and increases in the time constant for relaxation of LV pressure and coronary vascular resistance were noted. These indices of myocardial stunning were reversed after blocking neutrophil-endothelial cell interaction with monoclonal antibodies against CD18 or ICAM-1 receptors, and significant improvements were also obtained after either thromboxane or leukotriene receptor blockade. We conclude that immediate postoperative myocardial stunning results largely from reperfusion injury that occurs due to an acute inflammatory response to ischemia and reperfusion, and that stunning can be largely reversed with appropriate pharmacological intervention. PMID- 8461525 TI - Do deficiencies of endothelial derived relaxing factor contribute to myocardial stunning? AB - Myocardial stunning is a phenomenon in which ventricular function is depressed by prior ischemia and remains suboptimal when blood flow is resumed. It is also characterized by coronary vascular endothelial dysfunction that is related to the duration of ischemia and can result in protein leakage, myocardial hemorrhage, or increased coronary vascular resistance. It is thought that local vascular tone is regulated by endothelium derived relaxing factor (EDRF), a compound commonly believed to be identical to nitric oxide (NO). EDRF increases the effects of other vasodilators through the formation of cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Patients with various cardiovascular disorders have been found to have dysfunction in the EDRF system, and EDRF paradoxically produces vasoconstriction in atherosclerotic arteries. Similarly, EDRF stimulation of vasodilation due to acetylcholine, calcium ionophores, or platelets appears to be reduced in coronary arteries that have been damaged by ischemia and reperfusion. By increasing EDRF production or inhibiting its breakdown, EDRF precursors such as L-arginine, the superoxide radical scavenger superoxide dismutase, nitroglycerin, and nitroprusside all cause vasodilation by increasing NO levels in the setting of myocardial ischemia. These therapies may also improve local "microvascular" function, thereby improving ventricular function. PMID- 8461526 TI - Calcium and stunned myocardium. AB - Calcium administration during ischemia or at the onset of reperfusion is generally considered to be deleterious because cytosolic calcium is elevated at this time. In contrast, the administration of calcium antagonists before or during ischemia is protective. While calcium antagonists may not be beneficial when given after reperfusion, calcium administration during this period has been found to enhance the recovery of systolic and diastolic function of stunned myocardium. PMID- 8461527 TI - Adenosine and the stunned heart. AB - Adenosine is one agent under investigation as a therapeutic intervention of myocardial stunning. Adenosine caused numerous effects on the cardiovascular system through its interaction with A1 and A2 receptors. We investigated adenosine A1 receptor mediated mechanisms of cardiac protection in the stunned rat myocardium. Previous studies showed that both adenosine and R phenylisopropyladenosine (PIA), an A1 receptor agonist, prolonged the time to onset of ischemic contracture in ischemic isolated rat hearts. Phenylaminoadenosine, an A2 receptor agonist, did not have any effect, while receptor antagonists blocked adenosine and PIA action. Direct attenuation of the effects of myocardial stunning was observed by altering levels of interstitial fluid adenosine. Our laboratory has shown that administration of erythro-9(2 hydroxy-3-nonyl) adenine (EHNA; an adenosine deaminase inhibitor) to dogs subjected to left anterior descending coronary artery (LAD) occlusion followed by reperfusion results in dramatic increases in ischemic levels of interstitial fluid adenosine and postischemic myocardial function. Using a similar model in dogs, we have shown that exogenous intracoronary adenosine (50 micrograms/kg per min) augmented postischemic recovery of function, as assessed by significant enhancement (p < 0.01) of systolic wall thickness (7.0 +/- 3.0 pretreatment vs 5.7 +/- 1.7 controls). These data support the role for an adenosine A1 receptor mediated mechanism for protection against myocardial stunning. PMID- 8461528 TI - Effects of triiodothyronine on stunned myocardium. AB - Administration of thyroid hormone, triiodothyronine (T3), causes numerous cardiovascular effects such as increases in stroke volume, cardiac output, heart rate, and myocardial contractility, and decreases in systemic vascular resistance. Along with other stressors, cardiopulmonary bypass (CPB) has been associated with reduced levels of T3. We examined the effects of T3 on early postischemic myocardial recovery in rabbit hearts subjected to crystalloid perfusion to simulate a low T3 state, and in pig hearts following global ischemia due to CPB. Studies using the former system showed that T3 administration results in significantly improved developed pressure after reperfusion of mildly ischemic hearts compared to controls, without producing inotropic effects. In more severely stunned rabbit hearts, physiologic and 10 times physiologic doses of T3 produced significantly improved (p < 0.05) stroke work end-diastolic length compared to placebo treatment. T3 treated pigs undergoing CPB and subjected to 30 minutes of global normothermic ischemia experienced significantly enhanced recovery of left ventricular contractility compared to controls at 90 and 120 minutes post reperfusion. Neither placebo nor T3 affected myocardial adenosine triphosphate levels. These data show that T3 enhances recovery from myocardial stunning without producing acute inotropic effects. PMID- 8461529 TI - Bone mass, bone loss, bone density and fractures. PMID- 8461530 TI - The incidence of hip fracture in Europe. AB - Fragility fractures are now recognized as a major public health problem. Although the prevalence of all fractures is similar among men and women, the vast majority of osteoporotic fractures occur in elderly women. These comprise vertebral compression fractures, Colles' fracture at the wrist and hip fracture, and to a lesser extent fractures at other sites. The fracture of greatest socioeconomic consequence in Europe is hip fracture, which increases exponentially in incidence with age. The reasons for differences in age- and sex-specific incidence relate in part to the lower bone density of women at the time of maturity (peak bone density) and the accelerated bone loss that occurs after the menopause. Women live significantly longer than men, so that the prevalence of osteoporosis amongst elderly women is six-fold that of men. The age-specific incidence of hip fracture is rising in men and women in many countries, and if the current trends in the United Kingdom continue then the number of hip fractures occurring each year will more than double over the next 20 years. There is a marked geographic distribution in the incidence of hip fractures, even in Europe. Indeed the differences in incidence between communities is greater than the differences in incidence between sexes within communities. This suggests that the importance of gonadal insufficiency in women has been overemphasized and that other factors, probably relating to genetic or lifestyle factors affecting peak bone density, account for ecological differences in incidence of hip fracture between communities. PMID- 8461531 TI - The effect of age on bone collagen turnover as assessed by pyridinium crosslinks and procollagen I C-terminal peptide. PMID- 8461532 TI - Different characteristics of cervical and trochanteric hip fractures. PMID- 8461533 TI - The effect of natural and surgical menopause on the secretion of cytokines from human blood monocytes. PMID- 8461534 TI - The role of macrophage stimulating factor M-CSF in bone resorption. PMID- 8461535 TI - Macrophage colon-stimulating factor (M-CSF) is essential for differentiation rather than proliferation of osteoclast progenitors. PMID- 8461536 TI - Estrogen, cytokines, and the control of osteoclast formation and bone resorption in vitro and in vivo. PMID- 8461537 TI - Hormones in the coupling of bone resorption and formation. PMID- 8461538 TI - Local control of osteoclast function. PMID- 8461539 TI - A new model of osteopenia using ectopically induced bone: effects of parathyroid hormone and estradiol on bone turnover in induced bone. PMID- 8461540 TI - Binding of osteopontin to the osteoclast integrin alpha v beta 3. AB - Occupancy of the chicken osteoclast alpha v beta 3 integrin stimulates immediate cell signals. Peptides from osteopontin containing Arg-Gly-Asp and peptides from the osteopontin and bone sialoprotein sequences containing Arg-Gly-Asp stimulated immediate reductions in osteoclast cytosolic Ca2+. The changes in cytosolic Ca2+ required the Arg-Gly-Asp sequence, and were blocked by LM609, a monoclonal antibody to the alpha v beta 3 integrin. Osteoclast stimulation by the proteins through the integrin did not require immobilization since soluble peptides produced changes in cytosolic Ca2+ and inhibited osteoclast binding to bone particles and bone resorption. The decrease in cytosolic Ca2+ stimulated by osteopontin and related peptides was due to activation of a plasma membrane Ca(2+)-ATPase. Thus, the data suggest that ligand binding to the osteoclast alpha v beta 3 integrin results in a reduction in cytosolic Ca2+ which participates in regulation of osteoclast function. PMID- 8461541 TI - Prostaglandins: mechanisms of action and regulation of production in bone. AB - Prostaglandins (PGs), particularly PGE2, are produced by bone and have powerful effects on bone metabolism. PGs have an initial, transient, direct inhibitory effect on osteoclast function. However, the major long-term effect in bone organ culture is to stimulate bone resorption by increasing the replication and differentiation of new osteoclasts. PGs also stimulate osteoclast formation in cell culture systems. Stimulation of osteoclastic bone resorption may be important in mediating bone loss in response to mechanical forces and inflammation. PGs have a biphasic effect on bone formation. At relatively low concentrations or in the presence of glucocorticoids, the replication and differentiation of osteoblasts is stimulated and bone formation is increased. This increase is associated with an increase in production of insulin-like growth factor-I (IGF-I). However, at high concentrations or in the presence of IGF-I, PGE2 inhibits collagen synthesis. In osteoblastic cell lines this inhibition can be shown to occur at the level of transcription of the collagen gene. The stimulatory effect on bone formation has been demonstrated when PGs are administered exogenously, but it is not clear how endogenous PG production affects bone formation in physiological or pathologic circumstances. The production of PGs in bone is highly regulated. The major source appears to be cells of the osteoblast lineage. A major site of regulation is at the level of the enzyme PG endoperoxide synthase (cyclooxygenase or PGH synthase). PGE2 production and PGH synthase mRNA are increased by PTH and interleukin-1 and decreased by estrogen. Glucocorticoids probably act by a different mechanism, decreasing either arachidonic acid or PGH synthase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461542 TI - Prevention of corticosteroid bone loss. AB - Prolonged corticosteroid therapy is known to result in an increased risk of osteoporotic fracture, probably as a consequence of enhanced bone resorption and depressed bone formation. We examined the effects of prophylactic treatment with 1,25-dihydroxyvitamin D3 (calcitonin) and nasal salmon calcitonin on corticosteroid-induced bone loss in 103 patients being treated with long-term corticosteroids for the first time in a randomized, double-masked prospective study. Patients were randomly allocated to one of three groups receiving either calcium supplementation alone, calcium plus calcitriol, or calcium plus calcitriol and nasal salmon calcitonin. Treatment was given for 12 months. Bone mineral density (BMD) was measured every 4 months by dual-photon absorptiometry in the lumbar spine and femoral neck. Calcium supplementation alone did not prevent bone loss at either site. In the lumbar spine calcitriol, with or without nasal calcitonin, significantly reduced bone loss (p < 0.0001). Neither calcitriol alone nor calcitriol with calcitonin prevented bone loss at the femoral neck. These data suggest that treatment with calcium and calcitriol, or with calcium and intranasal calcitonin, greatly reduced or prevented corticosteroid-induced bone loss in the lumbar spine. PMID- 8461543 TI - Steroid osteoporosis. PMID- 8461544 TI - Systemic mastocytosis and osteoporosis. PMID- 8461545 TI - Estrogen: effects and actions in osteoporosis. PMID- 8461546 TI - Estrogen and bone. PMID- 8461547 TI - Calcium enhances the bone-sparing effects of low-dosage estrogen in postmenopausal women. PMID- 8461548 TI - Calcium supplementation in osteoporosis. AB - Although calcium is the most abundant inorganic constituent of the bone, indispensable for the maintenance of its physical strength, the role of calcium nutrition in the development of osteoporosis and the preventive and therapeutic significance of calcium supplementation in osteoporosis have been matters of intense controversy. The wide difference in the baseline nutritional intake of calcium among different groups and the variation in age of the patients studied may have been contributory factors. Emphasis has so far been placed on the rapid bone loss in the immediate postmenopausal period predominantly influenced by estrogen deficiency which has overshadowed the effect of calcium. The strong dependence of the effect of calcium preparation used tends to be forgotten. In the present study employing oyster shell electrolysate as the calcium source in patients with a mean age of approximately 80 years, bone mineral density was kept significantly higher than in age-matched, non-supplemented patients over a period of 2 years. In separate experimental studies, rats maintained on 2% calcium showed higher bone mineral content and lived longer than did controls maintained on 1% calcium. Age-associated deterioration of renal function and hyperlipidemia were also prevented by calcium supplementation. PMID- 8461549 TI - Epidemiology of hip fractures in the elderly: a cross-national analysis of mortality rates for femoral neck fractures. PMID- 8461550 TI - Prevention of osteoporosis: calcium nutrition. AB - Calcium is a threshold nutrient which means that a nutritional response in terms of calcium balance or bone mass will be present at intakes below the threshold and not above. The analogy can be made with the case of iron nutrition and anemia. Estimates of the threshold intake levels can be made for all stages of life based on available calcium balance data. They range between 1.3 g/day for infants to 1.5 g/day for women past menopause. Calcium nutrition is most important during growth and development in achieving genetically programmed peak skeletal mass. It is also important in maintaining bone mass in the elderly years. Calcium needs are supplied by the breakdown of the skeleton during the first few years after menopause, and thus calcium nutrition is less important until about 5 or 6 years after cessation of menses. Optimum calcium intake is best obtained from food sources; however, the lower food intake of modern humans compared with the food intake of humans during involution has resulted in difficulty in gaining an adequate intake of calcium. Calcium supplements are destined to become and important source of dietary calcium and thus some attention must be paid to their nutritional value. Solubility of a calcium salt is not a major determinant of absorbability over a range of 5 orders of magnitude of solubility. However, there is a well-defined enhancing effect of the co ingestion of a meal with calcium supplements. It would seem prudent to recommend that any calcium supplement be given at meal times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461551 TI - Exercise therapy for osteoporosis. AB - Our experimental and clinical studies lead to the following conclusions: 1. The amount of exercise that has a favorable effect on bone tissue differs between males and females among individuals. 2. An appropriate amount of exercise has a favorable influence not only on weight-bearing bone but also on non-weight bearing bone, provided there is a sufficient intake of calcium. 3. Exercise may prevent the bone loss in osteoporosis, but an increase in bone mass cannot be expected. The major aim is to increase bone mass before the achievement of peak bone mass in order to prevent osteoporosis. However, suitable weight-bearing exercise in osteoporosis is useful for the prevention of falls which may result in fractures, to increase muscle strength, to improve walking balance and coordination, and to prevent orthostatic hypotension. PMID- 8461552 TI - Exercise in the prevention of osteoporosis. PMID- 8461553 TI - Prevention of bone loss in postmenopausal and senile osteoporosis with vitamin D analogues. PMID- 8461554 TI - Total body absorptiometry in postmenopausal osteoporosis patients treated with 1 alpha-hydroxylated vitamin D metabolites. PMID- 8461555 TI - 24R,25-dihydroxyvitamin D3 increases bone mass in vivo. PMID- 8461556 TI - The development of vitamin D3 analogues for the treatment of osteoporosis. PMID- 8461557 TI - Treatment of postmenopausal osteoporosis with 1,25-dihydroxyvitamin D3. PMID- 8461558 TI - Vitamin D in bone formation. PMID- 8461559 TI - Human parathyroid peptide treatment of vertebral osteoporosis. AB - Previous studies have shown that treatment with daily injections of human parathyroid peptide (hPTH) 1-34 increase axial cancellous bone mass partially at the expense of peripheral cortical bone. In the present work the same hPTH 1-34 regime given for 12 months has been combined with oestrogen or nandrolone therapy to control peripheral bone resorption. Spinal and iliac cancellous (but not cortical) bone increased by 40%-50% above initial values while no perceptible changes occurred in radial cortical or cancellous bone. The evidence of radiokinetic and histomorphometric studies performed before and in the last months of treatment suggested that bone remodeling had proceeded through a transient anabolic phase with increased activation, but that activation had become normal after 11-12 months in the cancellous bone of the ilium whereas it continued to be raised elsewhere in the skeleton. It is concluded that in combination with oestrogens, hPTH peptides given daily injections hold great promise for the treatment of patients with osteoporosis who have already lost substantial amounts of spinal cancellous bone. PMID- 8461560 TI - Influence of age, sex and diet on bone mass and fracture rate. PMID- 8461561 TI - Treatment of postmenopausal osteoporosis with daily parathyroid hormone plus calcitriol. PMID- 8461562 TI - Calcitonin in the prevention and treatment of osteoporosis. PMID- 8461563 TI - Effect of salmon calcitonin nasal spray on bone mass in patients with high turnover osteoporosis. PMID- 8461564 TI - Fluoride salts for vertebral osteoporosis: the benefit-to-risk ratio depends on the cumulative dose reaching bone. PMID- 8461566 TI - Double-blind placebo-controlled trial of treatment of osteoporosis with the anabolic nandrolone decanoate. PMID- 8461565 TI - Fluoride treatment of osteoporosis: cyclical non-blinded or continuous blinded studies? AB - The future of sodium fluoride (NaF), the most potent osteoblast stimulator known to man, is in the balance. Of three recent randomized trials of continuous NaF only one found a significant in vertebral fractures in the NaF group. When data from the first year were excluded, two of the studies (those with the largest numbers) showed a significantly reduced risk of vertebral fracture on NaF. The effect of NaF on cortical bone is poorly documented. Two studies have shown reduced forearm cortical bone density with continuous NaF. A further two (histomorphometric) studies have shown the development of increased cortical porosity on continuous NaF treatment. In one, this was selectively at the external cortex and was linearly correlated with cancellous volume increase. Our pilot study using NaF administered cyclically has shown an encouraging (though non-significant) reduction in vertebral fracture rates (excluding year 1) and no fall in forearm cortical density. Another (US) cyclical study has shown no increase in cortical porosity. A current W. Australian randomized study of 50 patients is described where NaF dosage is varied proportional to the osteoblast response, and duration is dependent on densitometric and radiographic response. The future of NaF should involve cyclical administration, in cautious initial dosage (50-60 mg/day) of enteric-coated NaF, in conjunction with a potent inhibitor of resorption such as hormone replacement, bisphosphonates or calcitonin. PMID- 8461567 TI - Bisphosphonates and osteoporosis. PMID- 8461568 TI - Ipriflavone influences the osteoblastic phenotype in vitro. PMID- 8461569 TI - Epidemiology and prevention of osteoporosis in urbanized Asian populations. AB - The incidence rate of hip fracture in Hong Kong in 1989 was calculated from hospital admission data and the census population. The incidence rate has increased 3-fold since 1966 to reach 9 per 1000 in men and 13 per 1000 in women 80 years and over. The age-adjusted rate was comparable to that in Singapore but higher than that in Japan. A case-control study was conducted on 280 women and 120 men with hip fracture and 800 controls. The relative risk for hip fracture increased with a low calcium intake, being 2.9 (95% confidence interval 1.9 to 4.6) in the lowest quartile. The relative risk for hip fracture was also significantly increased in subjects who did not perform load-bearing activity every day. Osteoporosis may be prevented by an adequate calcium intake and load bearing activity in urbanized Asian populations. PMID- 8461570 TI - Bisphosphonates in osteoporosis? PMID- 8461571 TI - Risk factors for bone loss in healthy postmenopausal women. PMID- 8461572 TI - Determinants of peak bone mass in young adult women: a review. PMID- 8461573 TI - An integrated view of the role of the endocrine system in the genesis of the osteoporosis associated with aging. AB - Estrogen deficiency is the major determinant of increased bone resorption and bone loss occurring in early menopause (first 5-6 years). The increased bone resorption is probably caused by the release of immune system cytokines such as IL-1, IL-6 and TNF by osteoblasts, the biosynthesis of which is no longer suppressed by estrogen. PTH secretion, although decreased in early menopause, may also contribute to increased bone destruction because of the presence of cytokines such as IL-1 and TNF which increase the sensitivity of bone to the resorptive effects of PTH. For the same reasons, the bone-destructive effects of increased serum levels of PTH occurring in the late menopause may be exaggerated. PMID- 8461575 TI - Effect of pregnancy and lactation on maternal bone mass and calcium metabolism. PMID- 8461574 TI - Risk factors for osteoporosis. PMID- 8461576 TI - Risk factors for hip fracture in elderly Japanese women in Tottori Prefecture, Japan. PMID- 8461577 TI - The relationship between femoral neck strength, bone mineral content and fracture fixation strength: an in vitro study. PMID- 8461578 TI - Determinants of peak bone mass. PMID- 8461579 TI - Influence of body parameters on female peak bone mass and bone loss. PMID- 8461581 TI - Age- and gender-related changes of body composition in Japanese. PMID- 8461580 TI - Variation in spinal and femoral bone mass gain, energy and calcium intake during adolescence. PMID- 8461582 TI - Selection of postmenopausal women for pharmacologic osteoporosis intervention. PMID- 8461583 TI - Use of a rapid decrease in trabecular bone density in the early diagnosis of senile osteoporosis. PMID- 8461584 TI - Screening for osteoporosis by bone densitometry: a stratified intervention approach. AB - We have performed computer modelling of the relationship between bone mass, age and hip fracture in a conditional probability model using a national population of 100,000 postmenopausal women aged 50 who have their bone density measured once. The computer model very closely reproduced the actual number of fractures in a Western Australian population. Intervention to bone loss completely in subjects with the lowest bone density (below 1 SD below the mean) would prevent 0.42 of a hip fracture per patient treated if the whole population were treated. Halving the rate of bone loss in the whole population would reduce hip fracture by two-thirds. These data suggest that hormone replacement therapy, which is the most effective therapy for preventing bone loss but which has the most side effects, should be focused on subjects with bone mass below 1 SD below the mean. The remainder of the population could be targeted with a public health campaign based on the lifestyle factors of increased dietary calcium and exercise which have been shown to slow but not stop bone loss. PMID- 8461585 TI - Diagnosis of osteoporosis and assessment of bone mass by radiography: the most convenient procedure to reduce the risk of fracture. PMID- 8461586 TI - Incidence of hip fracture: an Italian survey. PMID- 8461588 TI - Some problems of dual-energy X-ray absorptiometry in the clinical use. PMID- 8461587 TI - Biochemical markers of bone turnover for the clinical investigation of osteoporosis. AB - The non-invasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include the serum measurement of total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of bone resorption can be achieved by measurement of urinary hydroxyproline, urinary excretion of the pyridinium crosslinks (pyridinoline and deoxypyridinoline), and by measurement of plasma tartrate-resistant acid phosphatase activity. For the screening of bone turnover in women at the menopause, and for the assessment of the level of bone turnover in elderly women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers, so far. Programs combining bone mass measurement and assessment of bone turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are made to develop more convenient assays and to identify other markers of bone turnover. In future a battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of bone metabolism that characterize the various aspects of osteoporosis. PMID- 8461590 TI - Bone histomorphometry. PMID- 8461589 TI - Bone densitometry: current assessment. PMID- 8461591 TI - [Results on the status of the organizational structures in hospital hygiene in Germany--I. Overall evaluation with special reference to acute hospitals]. AB - The results of an inquiry about the hospital hygiene in 2034 German hospitals demonstrate, that 35% of all hospitals have a hospital epidemiologist, 66% have infection control nurses and 86% infection control physicians. Infection control committees are present in 81% of German hospitals. 88% of all hospitals use the guideline of the Federal Public Health Office "On the Identification, Prevention and Control of Hospital Infections" as a basis for all decisions on hospital hygiene. PMID- 8461592 TI - [Genotoxicity--causes and sequelae]. AB - Genotoxicity is being increasingly focussed in both scientific and public discussions. This paper tries to point out the connections with mutagenicity and carcinogenicity and to show up several important medical aspects of DNA damage. PMID- 8461593 TI - [Information system on cancer mortality and district characteristics of the Rhineland TUV]. AB - On account of the lack of a comprehensive cancer registry with national coverage for the Federal Republic of Germany, the long-term and interregional evaluation of cancer mortality data is of particular relevance. Therefore, the TUV Rheinland instructed by the Federal Ministry for the Environment, Nature Protection, and Reactor Safety maintains an "Information System on Cancer Mortality and District Characteristics (IKK)" using official cause of death and resident population statistics. Mortality data for a variety of different cancer sites are documented with local and temporal separation for the area of the Federal Republic of Germany (before the German unification) and for a period of 20 years. The IKK data can be employed as a meaningful tool for epidemiological investigations relating to the correlation of cancer mortality and environmental agents. In the present paper the principles of the IKK are described and some examples of results are presented. PMID- 8461594 TI - [Results of studies from the AIDS counseling center of the Frankfurt/M. city health office January 1990 to December 1991]. AB - Between January 1990 and December 1991 5854 clients entered the AIDS-Counselling Service of the Municipal Health Department in Frankfurt/M; 1997 (34%) of them were female and 3857 (66%) male. In 5228 cases blood samples were examined for HIV-antibodies and the prevalence of positive tests was 84 (1.6%). Among the subjects who were seropositive for HIV, 51 (61%) were homosexual, 9 (11%) bisexual and 11 (13%) heterosexual men, furthermore 5 (6%) heterosexual women. 8 (9%) seropositive persons were intravenous drug abusers (5 male, 3 female). With the aid of an anonymous questionnaire that was filled in voluntarily by the clients, information about the sexual anamnesis, reasons for wanting the test, and whether they had been already tested for HIV in the past, could be gained. During the examined period, safer sex has been practiced by 414 (58%) of 712 homosexual men and by 1183 (24%) of 4867 heterosexuals (2923 male, 1944 female). By reason of a new partner 141 (19%) homosexuals and 1261 (26%) heterosexuals wanted to be tested for HIV; 529 (74%) homosexuals and 1806 (37%) heterosexuals had been already tested for HIV in the past. Summing up we can state, that the large attendance of the AIDS-Counselling Service, now as before, could be traced back to great acceptance and trust placed the population in the Municipal Health Department. HIV-testing is accepted by heterosexual and homosexual couples as well, and often performed at the beginning or at the end of a partnership. Safer sex plays, now as before, a subordinate role among heterosexuals in comparison to homosexuals. PMID- 8461595 TI - [Participation in the 1992 World Diabetes Day in the Ammerland district--a contribution to health promotion]. AB - Departments of Health can function as important initiators of health promotion on community level. This includes the support of efforts for cooperation ("corporate identity"). A one-day-project for the World Diabetes Day (June 27, 1992) in the Ammerland county (Lower Saxony) gives an insight on possible activities, results and conclusions. PMID- 8461596 TI - [100 years ago: the first school doctors in Leipzig--a contribution to the history of school health in Germany]. AB - One hundred years ago, in May 1892, the first school doctors began their work. The medical and organizational conditions for activities in school hygiene in Germany, their problematic linkage to "racial hygiene" and the military, and the favourable conditions for school medicine at the national and local levels and among members of the profession in Leipzig and Saxonia are presented. A description of the doctors' hygiene-oriented tasks in the schools completes the picture of the development of school hygiene in imperial Germany and in one of its richest cities. PMID- 8461597 TI - [A model project for geriatric rehabilitation in Rhineland-Pfalz]. PMID- 8461598 TI - [Discussion on implementation of a pilot project "Social medicine consultation" in the Mecklenburg-Vorpommern MDK (Medical Service of Health Insurance)]. PMID- 8461600 TI - [Proposal of the Society of German AIDS Foundations for singular support from the organization]. PMID- 8461599 TI - [Report of the status of HIV and AIDS in Germany]. PMID- 8461601 TI - The possible use of spleen cells for the adoptive immunotherapy of cancer patients. AB - The possible use of spleen-derived mononuclear cells (SPMC) for the intentional and economical adoptive immunotherapy of cancer patients was studied. SPMC were obtained from spleens resected surgically from patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). When SPMC were cultured in recombinant interleukin 2 (rIL2), SPMC, in the form of interleukin-activated killer spleen cells (IL-SP) proliferated in six of eight cases. CD8+ lymphocytes were the major expanding cell population in most SPMC cultures and IL-SP showed a significant cytolytic activity against cultured tumor cells during cell proliferation. When cultured with a streptococcal preparation, OK-432, for 24 to 48 h, SPMC showed cytotoxic activity against tumor cells and were expressed as OK-432 activated killer spleen cells (OK-SP). The effects of supernatants from IL-SP and OK-SP on tumor cell growth were also examined. The supernatants from IL-SP and OK-SP significantly inhibited cell growth in 3 and 10 out of 11 cases, respectively, while those from OK-SP showed higher growth inhibitory activity than those from IL-SP. The results of this study indicate the potential of SPMC as effector cells for the adoptive immunotherapy of cancer patients. PMID- 8461602 TI - Survival and recurrence after low anterior resection and abdominoperineal resection for rectal cancer: the results of a long-term study with a review of the literature. AB - Morbidity, survival, and recurrence in 203 patients treated with curative low anterior resection (LAR) were compared with those in 100 patients treated with curative abdominoperineal resection (APR). The overall 5-year survival figures for the total number of, LAR and APR patients were 75.6 +/- 5.7%, 79.8 +/- 6.4% and 67.7 +/- 9.6%, respectively. The prognosis for cancers situated low enough in the rectum to involve the anal canal was poor even when managed by APR, as evidenced by a low survival at 5 years of 59.0 +/- 9.6% and a high pelvic recurrence rate of 34%. For all except these tumors, LAR proved at least equal to, or better than APR as a curative surgical method for middle and low rectal cancers, on the basis of 5-year survival being 79.8 +/- 6.4% vs 78.7 +/- 5.2%, operative mortality being 1.5% vs 1.0%, morbidity being 39.4% vs 59.0%, and the incidence of pelvic recurrence being 8.9% vs 13.5%. When deciding upon the most appropriate surgical procedure for rectal cancer, especially for middle or low rectal lesions, the patient should not simply be condemned to a permanent colostomy. Thus, we first attempt LAR for every lesion except those which are very advanced or those with anal canal involvement, if technically feasible and suitable for the individual patient. PMID- 8461603 TI - Management of gallstones in cirrhotic patients. AB - 34 cirrhotic patients who underwent either cholecystectomy alone or in conjunction with common duct exploration were retrospectively reviewed. In Child A and B patients morbidity was low and there were no postoperative deaths. However, all patients who underwent additional cholecystectomy during the non shunting operation for esophageal varices required blood transfusion. Cholecystectomy in Child C patients is frequently associated with considerable intraoperative bleeding and subsequent postoperative complications. In the 23 patients who were not operated upon for gallstones, no patients developed symptomatic biliary disease. Ultrasonographically, most of these gallstones were strongly suspected to be black stones. Elective surgical intervention for symptomatic Child A and B patients would normally be warranted, but hemorrhage and resulting complications due to additional cholecystectomy for asymptomatic gallstones during the non-shunting operation should be minimized. An additional cholecystectomy should be considered, provided such a cholecystectomy is thought to be easily performed judging from the degree of development of collateral circulation around the hepatoduodenal ligament and unless black stones are suspected ultrasonographically. For symptomatic gallstones in Child C patients every type of medical treatment should be attempted. After considering the bleeding tendency or ascites, percutaneous transhepatic gallbladder drainage is considered to be one of the safest treatments. PMID- 8461604 TI - A study on postoperative enteritis caused by methicillin-resistant Staphylococcus aureus. AB - We investigated the production of staphylococcal enterotoxin (SE) with respect to coagulase types by methicillin-resistant Staphylococcus aureus (MRSA). A total of 138 strains of MRSA, which were isolated from clinical materials in the surgical ward between 1983 and 1990, were studied. Coagulase type IV strains produced SE A only, whereas coagulase type II strains were classified into four groups by SE production: SE B producing strains (32.7%), SE C producing strains (29.8%), SE B and C coproducing strains (12.5%), and SE A and C coproducing strains (25.0%). Almost all of the organisms (nine of ten) which were isolated from the feces of patients with MRSA enteritis were SE A and C coproducing strains. The coincidence in time of the prevalence of MRSA enteritis and the isolation SE A and C coproducing strains also demonstrated that these strains caused MRSA enteritis. Although SE C producing strains and SE A and C coproducing strains were simultaneously prevalent in 1990, the former tended to be sensitive while the latter tended to be resistant to minocycline. Considering the variety of antibiotic sensitivity in coagulase type II strains, it is thus considered to be of critical importance for epidemiologic purposes to further characterize isolates by SE typing. PMID- 8461605 TI - The effect of supplementing hypothermic crystalloid cardioplegia with catalase plus allopurinol in the isolated rabbit heart. AB - The effect of adding allopurinol and catalase to hypothermic cardioplegia for ischemic-reperfusion injury was investigated in the isolated rabbit heart. Hearts were divided into two groups, namely: Group C (n = 7), which received a hypothermic crystalloid cardioplegic solution alone (4 degrees C), and group T (n = 7), which received the hypothermic cardioplegic solution with allopurinol (148 mumol/L)13 and catalase (37 nmol/L).12 The cardioplegic solution was infused continuously into the isolated hearts, which had been placed in ice-cold saline, during a 12 h preservation. Subsequently, the hearts were mounted on a noncirculating, nonpulsatile perfusion circuit using Krebs-Henseleit buffer solution at 37 degrees C for 1 h at a constant perfusion pressure of 75 mm Hg. The left ventricular developed pressure (LVDP), maximum rate of pressure change (max dp/dt), and percent recovery of coronary flow were higher, while the creatine phosphokinase concentration and left ventricular end diastolic pressure (LVEDP) were lower in group T. The tissue malondialdehyde concentration and water content were similar in both groups. Thus, cardiac function after a 12 h preservation was enhanced by the added combination of allopurinol and catalase to the cardioplegic solution, supporting its role in the prevention of free radical reperfusion injury in cardiac preservation. PMID- 8461606 TI - Fibrinogen Osaka IV: a congenital dysfibrinogenemia found in a patient originally reported in relation to surgery, now defined to have an A alpha arginine-16 to histidine substitution. AB - We discovered a congenital heterozygous dysfibrinogen in a patient and reported this case in relation to surgery some time ago (Jpn J Surg (1988) 18:43-46). Further studies on the isolated abnormal population of fibrinogen derived from this patient have revealed that fibrinopeptide A was not cleaved by ancrod, a snake venom-derived thrombin-like enzyme, but by thrombin, slowly but completely. The released fibrinopeptide A components, being the A, AY, and AP peptides, were all found to be abnormal, as evidenced by slightly earlier elution positions on high-performance liquid chromatography, compared with the normal counterparts. By analyzing their amino acid sequence, we have identified an arginine to histidine substitution at position 16 of the A alpha chain, the thrombin cleavage site. Utilizing insolubilized abnormal fibrinogen, we confirmed that the polymerization site assigned to the central E domain, the "A" site, was exposed by thrombin, but not by ancrod. This dysfibrinogen, designated as fibrinogen Osaka IV, is the second abnormal molecule with an A alpha arginine-16 to histidine substitution identified among Japanese families. PMID- 8461607 TI - Modes of biliobiliary anastomosis in relation to the healing process and occurrence of postoperative stricture. AB - The inverting and everting methods of biliobiliary anastomoses were compared histopathologically and electron microscopically. Epithelialization started on the 3rd postoperative day and occurred within 8 mm of the anastomosis with an earlier and more active epithelialization being seen in the proximal area than in the distal. A rapid decrease of the mucosal defect was seen for 3-5 days which slowed down thereafter, and closure was achieved by 30 days after the anastomosis in both groups. The everted group showed a smoother and more rapid healing process, quicker epithelialization, and less mucosal defects than the inverted group. In the chronic phase, the inverted group showed more papillary hyperplasia and more pronounced fibrosis of the wall. The stricture index, being the internal circumference of the common bile duct: proximal x 2/anastomosis site + duodenal x 100, of the everted group was 123.7% compared to 146.7% for the inverted group, but there was no statistical difference. There was no difference in the total area of crypts, representing the epithelialization, between the two groups. Anastomoses with proximal dilatation therefore healed more slowly than those without dilatation. These findings show everted anastomosis to be superior to inverted anastomosis and thus support the usefulness of T-tube drainage to prevent postoperative dilatation of the bile duct. PMID- 8461608 TI - Extracorporeal cisplatin removal using direct hemoperfusion under hepatic venous isolation for hepatic arterial chemotherapy: an experimental study on pharmacokinetics. AB - This study was undertaken to pharmacokinetically evaluate the efficacy of direct hemoperfusion under hepatic venous isolation (HVI-DHP) to cisplatin (CDDP) removal during hepatic arterial infusion. CDDP (2-4 mg/kg) was administered continuously to mongrel dogs through the hepatic artery for 10 min. Plasma levels and tissue concentrations were then compared between animals receiving CDDP alone (group 1, n = 4) and those treated with additional HVI-DHP for 20 min (group 2, n = 6). The peak CDDP levels in the right external jugular vein (systemic level) were 6.10 +/- 1.31 (mean +/- SD) and 1.41 +/- 0.12 micrograms/ml in groups 1 and 2 at a dosage of 2 mg/kg, respectively (P < 0.01). The estimated drug removal rates in group 2 animals at dosages of 2 and 4 mg/kg were 45.7 (mean, n = 5) and 46.9% (n = 1), respectively. The tissue concentrations of CDDP of the liver 30 min after the initiation of infusions were similar in both groups. The values of the liver, the heart, and the kidney were 1.90 +/- 0.55, 0.50 +/- 0.16, and 3.90 +/- 2.50 micrograms/g of wet tissue weight, respectively, in group 1. In contrast, tissue levels of the heart and the kidney in group 2 animals were significantly reduced, with the values at a dosage of 2 mg/kg being 0.21 +/- 0.03 micrograms/g (P < 0.01) and 0.86 +/- 0.53 micrograms/g (P < 0.05), respectively. This study demonstrated that the extrahepatic distribution of CDDP during hepatic arterial infusion can be reduced significantly by the concomitant use of HVI-DHP. PMID- 8461609 TI - Superior mesenteric arteriovenous fistula: report of a case and review of the literature. AB - Iatrogenic arteriovenous fistula of the superior mesenteric vessels is rare, with only 22 cases being documented. We report herein a case of a 63-year-old man with an iatrogenic arteriovenous fistula which developed after a small bowel resection for intestinal tuberculosis. The patient was admitted to our hospital for a gastric ulcer, at which time an ultrasonogram demonstrated cystic dilatation of the superior mesenteric vein, proving to be an arteriovenous fistula of the mesenteric vessels. An angiogram of the superior mesenteric vessels subsequently confirmed this diagnosis and resection of the fistula was performed, followed by an uneventful recovery. Iatrogenic mesenteric arteriovenous fistula with no presenting symptoms, as in our case, is uncommon and surgery performed before the development of associated portal hypertension should achieve good results. A review of the literature follows the report of this case. PMID- 8461610 TI - Right common iliac arterio-intestinal fistula caused by tubercular peritonitis: report of a case. AB - A 59-year-old female was admitted with massive hematemesis and melena. A hematological examination revealed that the red blood cell count was 1.31 x 10(6)/mm3, Hb 3.4 g/dl, and Hct 12%. No source of bleeding was found by an emergency endoscopic examination of the esophagus, stomach and duodenum, or by superior mesenteric angiography. At laparotomy a right common iliac arterio intestinal fistula was found. The microscopic examination of this part of the ileum, including the fistula, revealed the presence of tubercular peritonitis. An extra-anatomic bypass graft using a prosthetic graft was performed between the left and right femoral arteries because reconstruction of the right common iliac artery was impossible. PMID- 8461611 TI - Primary squamous cell carcinoma of the breast after cured Hodgkin's disease. AB - An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkin's disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkin's disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkin's disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkin's disease. The risk of patients treated for Hodgkin's disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case. PMID- 8461612 TI - DNA ploidy, c-myc oncoprotein p62 and v-H-ras oncoprotein p21 in colorectal carcinoma. AB - DNA ploidy and expression of the c-myc oncoprotein p62 and the v-H-ras oncoprotein p21 were examined in 54 colorectal carcinomas. DNA ploidy, determined by DNA flow cytometry, was diploid in 19 samples and aneuploid in 35. Expression of the p62 oncoprotein, determined by immunohistochemical staining, was intensely positive in 18 samples while that of the p21 oncoprotein, also determined by immunohistochemical staining, was positive in 29. There was no correlation between DNA ploidy and expression of the p62 oncoprotein, and DNA ploidy did not correlate with expression of the p21 oncoprotein. There was, however, a close correlation between expression of the p62 oncoprotein and that of the p21 oncoprotein being P < 0.01 according to Peason's chi-square test. PMID- 8461613 TI - The outcome of patients with thyroid carcinoma and Graves' disease. AB - A total 847 consecutive patients with Graves' disease who underwent thyroidectomy between 1965 and 1990 were found to have a 4.3% incidence of coincident carcinoma of the thyroid. In 68.2% of these cases the tumors were less than 1 cm in diameter and were detected in only 7 patients (19.4%) prior to surgery. Dissection of the regional lymph nodes was necessary in only 11 patients. A review of the patients in 1990 revealed no carcinoma-related deaths with metastases occurring most commonly in the patients with larger tumors and in those whose cancer had been detected prior to thyroidectomy. Although the detection of potential tumors occurring with Graves' disease using preoperative echogram may be of interest, our results suggest that occult microcarcinoma occurring coincidentally with Graves' disease is not clinically significant as it did not cause any recurrence in this study. Moreover, there was no evidence to suggest that Graves' disease was associated with the increased or rapid growth of these tumors. PMID- 8461614 TI - Building choice opportunities within occupational programmes for persons with profound developmental disabilities. AB - Choice opportunities were arranged within the occupational programmes of two subjects with profound developmental disabilities. The subject participating in Experiment 1 was already familiar with a computer-aided programme aimed at promoting independent occupation. That programme was now extended to allow him to choose activities and reinforcers. He was also exposed to a control programme involving the use of folders with drawings. The subject participating in Experiment 2 had no previous experience with special programmes. For this subject, two versions of a computer-aided programme were used: one to teach occupational engagement without choice; and the other occupational engagement with choice. The results have shown that the first subject was very successful in combining choice behaviour and constructive activity with the computer-aided programme, but not with the control programme. The second subject learned very rapidly independent activity engagement, but required relatively long time to develop 'meaningful' choice behaviour. General implications of the findings are discussed. PMID- 8461615 TI - Effects of a community-based service on adaptive and maladaptive behaviours: a longitudinal study. AB - Changes in skill acquisition and problem behaviour, contingent upon the introduction of a new community-based service, were compared for subjects in three different residential settings: supported accommodation; hospital; and private family homes. Results over a 5-year period indicate links between service contact and increases in skill level, together with an increase in problem behaviour for subjects who moved from hospital to supported accommodation. The interpretation of client income in the context of service process is discussed. PMID- 8461616 TI - Service use among school leavers with severe learning difficulties: the views of carers. AB - School leaving is a time when difficult decisions have to be taken. Difficulties are likely to be particularly complex when the school leaver has severe learning difficulties. Carers of 61 young people living in one East London Health District were interviewed about their child's experience of service use at around the time of school leaving. The timing of school leaving appears to have been well handled, and the experience of those who went on to further education was positive. The school social work service was greatly appreciated. On the debit side, many informants were critical of the quality of short-term residential care. The commonest concern was for the prompt availability of day care. As in the few other studies of this subject, the impression that services appeared uncoordinated was given by carers. PMID- 8461617 TI - Factor structure of the Motivation Assessment Scale. AB - The Motivation Assessment Scale (MAS) was developed to provide clinical information on four hypothesized functions that may control problem behaviour in persons with developmental disabilities. The original four-factor structure of the MAS was based on face validity, with the items being grouped in terms of each of the hypothesized functions. Validation of the scale was provided in terms of correlations between teacher ratings of eight children on the MAS and ranking of the controlling variables from functional analogue tests. In this study, staff in residential facilities rated 60 residents and teachers in schools rated 96 students on the MAS. The target behaviour rated for both samples was self-injury, with the institutional sample engaging in the behaviour more than 15 times an hour and the school sample, less than 15 times an hour. The results of factor analyses, with varimax rotation, provided a conceptually meaningful factor structure with the institutional sample, but not with the school sample. The 16 MAS items resolved into four factors that were conceptually related to four conditions that may maintain problem behaviour (i.e. sensory, escape, attention and tangible). The results suggested that the original MAS has a robust factor structure and may be clinically useful in predicting the controlling functions of problem behaviours, if the target behaviours occur at a rate no less than 15 responses per hour. PMID- 8461618 TI - A scale of attitudes toward the application of eugenics to the treatment of people with mental retardation. AB - As part of a larger study of the attitudes of diverse samples towards the application of eugenics to the treatment of people with mental retardation, a 32 item summated rating scale was developed as a contemporary, brief, easy to administer and score, and psychometrically sound instrument. Data were collected and analysed that indicated satisfactory item characteristics and reliability, and initial support for the content and construct validities of the scale. Analyses of social desirability data revealed that scale scores were not influenced by the subjects' desire to adhere to socially desirable expectations. The scale should be useful for the investigation of questions concerning the formation, structure and correlates of attitudes toward the application of eugenics to the treatment of people with mental retardation, and the relationship of these attitudes to contemporary mental retardation policies and practices. PMID- 8461619 TI - Asperger's syndrome: three cases and a discussion. AB - The recently revived academic interest in and controversy over the subject of Asperger's syndrome is briefly discussed. Gillberg & Gillberg's operational criteria for its definition are used to isolate three cases of the syndrome presenting over a single year to a mental handicap service. The cases are described in detail. Common themes and associations with the available literature are discussed. In all three cases, the struggle for clarity in the syndrome's nature or specificity in the literature is also reflected in aspects of their clinical management. PMID- 8461620 TI - An analogue assessment of hand stereotypies in two cases of Rett syndrome. AB - Stereotype hand movements are one behavioural manifestation of Rett syndrome, a neurodegenerative disorder resulting in severe mental retardation. They are neuropathological in origin, and constitute a barrier to the acquisition and exhibition of more developmentally appropriate behaviours, as well as posing a health risk for some individuals. The present study used an analogue assessment procedure, in which experimental conditions were constructed varying in the consequences delivered contingent upon the exhibition behaviour, to examine environmental correlates to the moment-to-moment expression of these behaviours. Results are discussed regarding their implications for intervention and research into the aetiology of stereotypic behaviours. PMID- 8461621 TI - Children of alcoholic parents: health, growth, mental development and psychopathology until school age. Results from a prospective longitudinal study of children from the general population. AB - Of 640 women who paid their first visit to the two maternal welfare centres in a new Stockholm suburb during one prospective year, 532 (85%) were interviewed with regard to 41 stress factors forming a "life stress score" (LSS). The interviews were supplemented with data from hospital, social welfare and police records concerning the expectant mother and the father. The 532 mothers were divided into three groups according to the degree of psychosocial stress (group 1 (n = 194) without psychosocial stress; group 2 (n = 171) with severe psychosocial stress; and group 3 (n = 167) in an intermediate group). In group 2, there were 23 mothers and 51 fathers in 64 families known to suffer from alcoholism/heavy drinking at the time of the first interview and these comprised our study group. The pregnancies and deliveries in the families were investigated with prospective methods. There were 497 liveborn children of whom 54 were born into families known for alcoholism/heavy drinking. The physical health and development of the children was followed by prospective data from the child welfare centers. Data concerning psychological development and psychiatric health of the child were obtained by interviewing the mother and evaluating the child during visits at home at one and four years of age. At one year of age, 452 of the children (226 boys, 226 girls) and at four to five years of age, 412 of the children (202 boys, 210 girls), were evaluated using the Griffiths' Development Scales. Findings from these evaluations form the basis for comparison of development of children from alcoholic/heavy drinking parents with all other children. For 388 children, data were available from all examinations up to the end of the fourth year, including 38 children (12 boys, 26 girls) in the study group and 350 other children (183 boys, 167 girls). The present findings indicate that children of alcoholic parents in the general population who were followed from pregnancy up to the end of their fourth year have a higher risk of pre- and postnatal death, and have poorer mental development and more symptoms of a psychopathological child psychiatric nature (DSM-III) than other children. Differences related to physical development during infant years disappeared during the observation time. With regard to mental development over a longer period, it appears that factors related to the parent's addictions and the child's sex (i.e. male child) are more important than pediatric risk factors in the form of a score of reduced optimality. PMID- 8461623 TI - Screening for thyroid disorders in a working population. AB - Subclinical thyroid disorders have received increasing attention in recent years due to refined laboratory methods and a stronger emphasis on the role of preventive medicine. We performed a screening for thyroid-stimulating hormone (TSH) on 6884 persons in a working population. In cases in which TSH was not within the normal range we also measured the levels of triiodothyronine (T3), thyroxine (T4), and thyroxine-binding globulin (TBG). All persons who did not present with exclusion criteria or other nonthyroidal illnesses (n = 59) and the controls (n = 39) were submitted to thyrotropin-releasing hormone (TRH)-testing. Additionally, sonography of the thyroid was performed on 120 persons (59 subjects with abnormal hormone levels and 61 controls) to determine thyroid size and rule out morphological abnormalities. Based on the TRH test and T3, T4, and TBG measurements we found a prevalence of 0.03% (2/6884) for overt hyperthyroidism, 0.33% (23/6884) for subclinical hypothyroidism, 0.09% (6/6884) for subclinical hypothyroidism, and 0.015% (1/6884) for overt hypothyroidism in the healthy population. In subjects with overt or subclinical hyperthyroidism the prevalence of goiters (thyroid volume > 18 ml in women, > 25 ml in men) was 28%. Of this group 48% had structural abnormalities. All persons with goiters and/or structural abnormalities were over 35 years of age. Among the euthyroid, 20% had thyroid enlargement, and the same proportion presented with structural abnormalities. There were no differences between the two age groups. In the group with overt/subclinical hypothyroidism 47% presented with structural abnormalities of the thyroid; however, none presented with thyroid enlargement. Thyroid nodules were found only in older persons (> 35 years) with euthyroidism or hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461622 TI - Granulocyte-macrophage colony-stimulating factor in the sera of patients with aplastic anemia. AB - To clarify the role of growth factors in the pathophysiology of aplastic anemia we measured serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in 33 aplastic anemia patients by a specific and sensitive enzyme-linked immunosorbent assay. GM-CSF serum levels of patients with aplastic anemia were significantly higher than in healthy volunteers. GM-CSF levels were correlated with the severity of aplastic anemia but not with the absolute neutrophil count. Since T lymphocytes are one of the main sources of GM-CSF, our data provide further evidence for in vivo T lymphocyte activation in aplastic anemia. GM-CSF serum levels are higher in patients responding to immunosuppressive treatment than in nonresponders. Elevated serum GM-CSF might be predictive of a good response to immuno-suppressive therapy. GM-CSF serum levels are lower immediately after treatment with antilymphocyte globulin/antithymocyte globulin (ALG/ATG) than corresponding pretreatment values. Thus we cannot confirm the hypothesis that ALG/ATG effects in vivo are mediated by stimulating the release of growth factors. We conclude that in aplastic anemia the primary defect is a failure in GM-CSF response rather than in GM-CSF supply. PMID- 8461624 TI - Primary and secondary microcirculatory disorders in essential hypertension. AB - In this prospective cross-sectional study blood fluidity and peripheral microcirculation were measured in patients suffering from essential hypertension with and without macroangiopathy. The cutaneous microcirculation was evaluated by intravital microscopy and the intramuscular by pO2 needle electrode. Disorders in the microcirculation without macroangiopathy in the system of the feeding arteries are defined as primary microangiopathy. Disturbed microcirculation with macroangiopathy in the feeding arteries in one area but no detectable microcirculatory disorder in another region is defined as a secondary microcirculatory disorder. Of the 57 patients in this study 27 had a primary microcirculatory disorder. It was remarkable that all 27 hypertension patients had a microcirculatory disorder in the area of the skin. Intramuscular microcirculatory disorder on its own without affection of the skin was not detected in any case. An exclusively secondary microcirculatory disorder occurred in 16 patients. This study shows that 93% of the patients with long-term essential arterial hypertension have microcirculatory disorders. It is most interesting that about one-half of these hypertension patients had a primary microcirculatory disorder, i.e., no indication of a hemodynamically active stenosis was found in the large vessels. PMID- 8461625 TI - Stepwise development of a clinical expert system in rheumatology. AB - The evaluation of computer expert systems, a promising diagnostic tool for future application in clinical medicine, is of great importance. We present here the evaluation of our expert system, "RHEUMA". It is stressed, that repeated retrospective testing and updating of an expert system and its subsequent repeated assessment in clinical use and surroundings is mandatory. This increases the diagnostic accuracy of the system. For our system this is demonstrated under three separate conditions. In the first study the information available for the computer system (mainframe) came from medical histories only. Here an error rate of about 25%--similar to that of physicians themselves using the same information -was observed in 358 outpatients, compared to the final diagnoses of physicians also relying solely on information from medical histories. In a second step a completely new system on a personal computer was developed with all relevant diagnostic information. The error rate of this system (0.4%) was much too optimistic because the knowledge base was changed during the study, affecting about 30% of the 282 prospectively recruited outpatients. In a third step the efficacy of the expert system was tested in an additional hospital without the diagnostic involvement of the first testing clinic. The error rate of the system without changing the knowledge base reached 11% in 51 outpatients in this rheumatology clinic. This result reflects the diagnostic accuracy of the system today. Its ability to specify the same diagnoses which clinical experts reached approached 90%. Considerable time is needed for such prospective testing, with repeated updating of the knowledge base--in our case for both the two systems and field studies of 2 years each.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461626 TI - Lipoprotein (a), low-density, intermediate-density lipoprotein, and blood pressure in a young male population. AB - Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a)[Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26 +/- 7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a). PMID- 8461627 TI - Aneurysms of coronary arteries in a patient with adult polycystic kidney disease: arteriosclerosis or involvement by the primary disease? AB - Adult polycystic kidney disease is frequently associated with gastrointestinal and cardiovascular abnormalities. These include hypertension, mitral valve prolapse, mild dilation of the aortic root, abdominal aneurysms, and predisposition to aortic, mitral, and tricuspidal valve regurgitation reminiscent of Marfan's syndrome. Although the exact molecular mechanisms of adult polycystic kidney disease are not well established, a generalized defect of collagen structure is hypothesized. The most severe vascular problems, however, are typical intracranial aneurysms with a high incidence of subarachnoid hemorrhage and a high mortality rate. We report a case of dilated coronary arteries found incidentally in a patient with adult polycystic kidney disease and stress-induced angina pectoris. The typical angina pectoris of the patient is explained by left ventricular hypertrophy and coronary heart disease. Multiple liver cysts, mitral valve prolapse, and the coronary aneurysms in this patient with adult polycystic kidney disease appear to reflect the manifestation of a generalized connective tissue disorder in this syndrome. PMID- 8461629 TI - Allopurinol and oxypurinol in human breast milk. AB - To pregnant or breast feeding women drugs should be given with caution. We report the case of a 5-week-old breast-fed infant whose mother was taking 300mg allopurinol/day for 4 weeks. Allopurinol and oxypurinol were detected by HPLC in maternal plasma and breast milk with a method first described here. In infant's plasma taken 2 h after breast feeding oxypurinol was found; allopurinol was below the limit of detection. The milk/plasma ratio in the mother 2 h (4 h) after drug ingestion was 0.9 (1.4) for allopurinol and 3.9 (2.4) for oxypurinol. The average daily dose for the baby of allopurinol was 0.14-0.20 mg/kg and that of oxypurinol 7.2-8.0 mg/kg by ingestion of breast milk after oral intake of allopurinol by the mother. PMID- 8461628 TI - Cellular signaling by cyclosporine A in contractile cells: interactions with atrial natriuretic peptide. AB - Immunosuppressive therapy with cyclosporine A (CyA) may be associated with severe side effects such as nephrotoxicity and arterial hypertension. The partial reversibility of these effects suggests that they are at least in part functional. The present study examined the effects of CyA on cellular signaling in vascular smooth muscle cells and in glomerular mesangial cells and the interactions with the endogenous vasodilator atrial natriuretic peptide (ANP). Intracellular free calcium concentrations ([Ca2+]i) were measured using Fura-2. 45Ca2+ was used to measure Ca2+ efflux and cellular Ca2+ influx. In the presence of cyclosporine (10 micrograms/ml), the Ca(2+)-mobilizing effects of angiotensin II (10(-8)M) in smooth muscle cells and of arginine vasopressin (AVP) in mesangial cells were significantly enhanced. CyA significantly stimulated cellular Ca2+ uptake in both cell types. ANP blocked the Ca2+ mobilization by angiotensin II and AVP and also completely inhibited the potentiating effect of CyA on angiotensin II- and AVP-induced Ca2+ mobilization. ANP also completely blocked the CyA-stimulated Ca2+ uptake. These findings suggest that CyA stimulates transmembrane Ca2+ influx, thereby increasing vasopressor-sensitive intracellular Ca2+ stores and augmenting vasopressor-induced Ca2+ mobilization. This cellular effect of CyA in vitro was markedly diminished by ANP. The effects of CyA on intracellular signaling may directly enhance the contractile response of smooth muscle and the glomerular mesangium to vasopressor stimuli and may also contribute to other disturbances of cell metabolism associated with CyA. PMID- 8461630 TI - Cefotaxime desensitization. AB - We report the successful desensitization to cefotaxime in a patient with severe lumbar osteomyelitis of unknown bacteriology and hypersensitivity to the drug. Desensitization was carried out because of the unknown bacteriology, the favorable response to cefotaxime at that time, and hypersensitivity to other antibiotics. On the first day the patient received 1 mg cefotaxime intravenously. The dose was increased for 13 successive days to 4 g cefotaxime intravenously per day. No allergic reaction occurred during desensitization or within 4 weeks of observation under this therapy. Patients with severe infections of unknown bacteriology might benefit from desensitization if therapy with a second-choice antibiotic is impossible. PMID- 8461631 TI - Laudatio to Professor Dr. N. Zollner on the occasion of his 70th birthday. PMID- 8461632 TI - New clues to the pathophysiology of hepatorenal failure. AB - In patients with advanced liver disease, decreases in renal blood flow, glomerular filtration rate, and urinary output are frequently observed. The deterioration in renal function is usually not due to a unique cause but is the result of the concerted action of several mechanisms operating in parallel; decreased plasma protein formation and increased intrahepatic vascular resistance lead to sequestration of blood volume, favoring hypovolemia and reduction in cardiac output. At the same time enhanced formation of nitroxide leads to peripheral vasodilation; bacterial endotoxin escaping clearance by the diseased liver stimulates the expression of a long-acting nitroxide synthase. Furthermore, vasodilating intestinal mediators such as substance P escape inactivation by the liver. In the face of peripheral vasodilation the maintenance of blood pressure requires an increase in cardiac output, which is achieved by activation of sympathetic nervous tone, renal vasoconstriction, enhanced release of renin, angiotensin, aldosterone, and antidiuretic hormone, leading to renal retention of sodium and water. Renal vasoconstriction is opposed by vasodilatatory prostaglandins, and renal failure may be triggered by inhibition of prostaglandin formation. On the other hand, vasoconstrictive eicosanoids, such as thromboxane B2 and leukotriene E2, which escape hepatic inactivation, may contribute to renal vasoconstriction. Beyond these mechanisms disturbed hepatic regulation of renal function may participate in the generation of hepatorenal syndrome. The liver regulates renal function via both a hepatorenal reflex decreasing renal blood flow and a hypothetical liver-borne diuretic factor increasing renal blood flow. Both enhanced hepatorenal reflex activity and decreased formation of the liver borne diuretic factor could participate in the pathogenesis of hepatorenal syndrome. PMID- 8461634 TI - The past of the future of medicine. PMID- 8461633 TI - Lung transplantation. AB - The indications and results of single and double lung transplantation are described on the basis of 66 operations performed by the authors and on the background of the world literature. Lung transplantation is considered a new and promising therapeutic mode for treating patients with end-stage pulmonary failure related to fibrosis, emphysema, infective conditions, and pulmonary hypertension yielding satisfactory early results. The long-term prognosis of patients undergoing lung transplantation, like that of any other organ transfer, remains guarded. PMID- 8461635 TI - Called by God, led by men: women face the masculinization of American medicine at the College of Medical Evangelists, 1909-1922. PMID- 8461636 TI - Bodies of the past. Essay review. PMID- 8461637 TI - The beginnings of the tobacco controversy: puritanism, James I, and the royal physicians. PMID- 8461638 TI - "Helps for Suddain accidents": Stephen Bradwell and the origin of the first aid guide. PMID- 8461639 TI - The conceptualization of influenza in eighteenth-century Britain: specificity and contagion. PMID- 8461640 TI - Early nutrition and diabetes mellitus. PMID- 8461641 TI - Improving medical education. PMID- 8461642 TI - Pre-emptive analgesia. PMID- 8461643 TI - Selective decontamination of the gut. PMID- 8461644 TI - The language of health. PMID- 8461645 TI - Use of tumour marker immunoreactivity to identify primary site of metastatic cancer. AB - OBJECTIVES: To determine whether variations in the expression of tumour related antigens can predict the origin of tumours. DESIGN: Immunohistological study of tumour marker expression in primary adenocarcinomas and respective metastatic deposits. Antibodies to the following tumour markers were used: polymorphic epithelial mucin (NCRC-11 and SM3), carcinoembryonic antigen, carcinoembryonic antigen with non-specific antigen co-specificity, CA125, CA19.9, prostate specific antigens, and thyroglobulin. SETTING: Histopathology department of teaching hospital. SUBJECTS: 100 pathology sections of metastatic adenocarcinoma and their related primary tumours. MAIN OUTCOME MEASURES: Concordance of reactivity between primary and metastatic tumours. Reactivity profiles of tumour sites. RESULTS: The correct primary site of origin was predicted in 70% (33/47) of tumours in men and 54% (27/43) tumours in women with antibodies SM3, 288, CA19.9, CA125, and PSA (men only). Specificities ranged from 68% for breast tumour to 98% for prostate tumour. CONCLUSION: Use of tumour markers in patients presenting with metastatic adenocarcinoma of unknown origin can help localise the probable primary sites and reduce the need for extensive and expensive imaging techniques. PMID- 8461646 TI - Who's afraid of informed consent? AB - OBJECTIVE: To test the assumption that patients will become unduly anxious if they are given detailed information about the risks of surgery in an attempt to obtain fully informed consent. DESIGN: Preoperative anxiety assessed before and after patients were randomly allocated an information sheet containing either simple or detailed descriptions of possible postoperative complications. SETTING: Four surgical wards at two Sheffield hospitals. SUBJECTS: 96 men undergoing elective inguinal hernia repair under general anaesthesia. MAIN OUTCOME MEASURE: Change in anxiety level observed after receiving information about potential complications. RESULTS: Detailed information did not increase patient anxiety (mean Spielberger score at baseline 33.7 (95% confidence interval 31.3 to 36.2), after information 34.8 (32.1 to 37.5); p = 0.20, paired t test). A simple explanation of the facts provided a statistically significant degree of reassurance (mean score at baseline 34.6 (31.5 to 37.6), after information 32.3 (29.8 to 34.9); p = 0.012), although this small effect is likely to be clinically important only in those whose baseline anxiety was high (r = 0.27, p = 0.05). CONCLUSIONS: In men undergoing elective inguinal hernia repair a very detailed account of what might go wrong does not increase patient anxiety significantly and has the advantage of allowing patients a fully informed choice before they consent to surgery, thus reducing the potential for subsequent litigation. PMID- 8461647 TI - Inherited prion disease (PrP lysine 200) in Britain: two case reports. AB - OBJECTIVE: To identify cases of inherited prion diseases in Britain and to assess their phenotypic features. DESIGN: Screening study of patients suspected clinically to have Creutzfeldt-Jakob disease and other neurodegenerative diseases by prion protein gene analysis. SETTING: Biochemical research department. SUBJECTS: Patients suspected to have Creutzfeldt-Jakob disease and other neurodegenerative diseases. RESULTS: Two patients with symptoms characteristic of sporadic Creutzfeldt-Jakob disease were found to have inherited prion protein disease (PrP lysine 200), with a mutation at codon 200 of the prion protein gene. Both were homozygous at codon 129 of the gene. One patient was a man aged 58 of British descent while the other was of Libyan Jewish origin. CONCLUSION: Two foci of inherited prion disease are known, among Libyan Jews and in Slovakia. A separate British focus of the disease may also exist. Heterozygosity at codon 129 may lead to reduced penetrance of the mutation. PMID- 8461648 TI - Association of low birth weight with beta cell function in the adult first degree relatives of non-insulin dependent diabetic subjects. AB - OBJECTIVE: To examine the relation between birth weight and beta cell function in the first degree relatives of non-insulin dependent diabetic subjects. DESIGN: Cross sectional study of 101 adults of known birth weight from 47 families which had at least one member with non-insulin dependent diabetes. SUBJECTS: 101 white adults aged mean 43 (SD 7) years. SETTING: Oxfordshire, England. MAIN OUTCOME MEASURES: Glucose tolerance was measured by continuous infusion glucose tolerance test. beta cell function and insulin sensitivity were calculated from the fasting plasma glucose and insulin concentrations with homeostasis model assessment. beta cell function was standardised to allow for the confounding effects of age and obesity. RESULTS: Twenty seven subjects had non-insulin dependent diabetes, 32 had impaired glucose tolerance, and 42 were normoglycaemic. Birth weight correlated with the beta cell function of the complete cohort (rs = 0.29, p = 0.005), the non-insulin dependent diabetic subjects (rs = 0.50, p = 0.023), and the non-diabetic subjects (rs = 0.29, p = 0.013). The non-insulin dependent diabetic (n = 27) and the non-diabetic (n = 74) subjects had similar mean (inter quartile range) centile birth weight 50% (19%-91%), and 53% (30%-75%) respectively. Non-insulin dependent diabetic subjects had significantly lower beta function than the non-diabetic subjects: 69% (48%-83%) v 97% (86%-120%), p < 0.001. CONCLUSIONS: The cause of the association between low birth weight and reduced beta cell function in adult life is uncertain. Impaired beta cell function in non-insulin dependent diabetic subjects was not accounted for by low birth weight, and genetic or environmental factors are likely to be necessary for development of diabetes. PMID- 8461649 TI - Effect of using safer blood products on prevalence of HIV infection in haemophilic Canadians. Canadian Hemophilia Clinic Directors Group. PMID- 8461650 TI - Time of presentation, time of operation, and unnecessary appendicectomy. PMID- 8461651 TI - General practitioners in partnership with management: an organisational model for debate. AB - The role of general practitioners is changing and expanding. Doctors have more control over the treatment received by their patients but remain largely unaccountable to the public and management. This article proposes an organisational model for integrating primary and secondary care which retains the advantages of fund-holding while giving management control over overall strategy. It proposes that general practitioners control funds for all primary and secondary care. Secondary care will be contracted through a joint team of managers and an elected general practice executive committee. A new health care purchasing authority will contract for primary services with individual practices or primary care provider units. General practitioners will have local contracts reflecting their desire to provide an expanded range of services and the needs of the community. PMID- 8461652 TI - FHSAs and prescribing. PMID- 8461653 TI - Making change happen. PMID- 8461654 TI - Primary care development zones. AB - Most commentators on the Tomlinson report have agreed with its emphasis on improving primary and community care. The three elements of such a strategy are a remedial programme to bring primary care up to national standards, a programme to provide such services to people with non-standard needs such as mobile Londoners, ethnic minorities, and homeless people, and the development of an expanded model of primary care. No one model will be appropriate across all of London. The process should start with an audit of existing resources and services within each community, together with an analysis of needs. From this would develop a local programme with specific plans for investment in premises, staffing, training, and management. New contractual mechanisms may be needed to attract practitioners, improve their premises, secure out of hours services, and provide medical cover for community beds. There should also be incentives for closer working between primary and secondary services. No developments on the scale needed for London have been carried out in primary care within the lifetime of the NHS--but their success will be critical to the calibre of health services for Londoners into the next century. PMID- 8461655 TI - Alternative allergy and the GMC. PMID- 8461656 TI - Alternative allergy and the GMC. PMID- 8461657 TI - Alternative allergy and the GMC. PMID- 8461658 TI - Alternative allergy and the GMC. PMID- 8461659 TI - Alternative allergy and the GMC. PMID- 8461660 TI - Alternative allergy and the GMC. PMID- 8461661 TI - Alternative allergy and the GMC. PMID- 8461662 TI - Alternative allergy and the GMC. PMID- 8461663 TI - Alternative allergy and the GMC. PMID- 8461664 TI - Self monitoring of blood glucose. PMID- 8461665 TI - Paget's disease of bone. PMID- 8461666 TI - Architecture of cancer. PMID- 8461667 TI - Avoiding exposure to HIV and hepatitis. PMID- 8461668 TI - Avoiding exposure to HIV and hepatitis. PMID- 8461669 TI - Avoiding exposure to HIV and hepatitis. PMID- 8461670 TI - Irish vote against abortion. PMID- 8461671 TI - Tomlinson report. PMID- 8461672 TI - Looking through a bubble. PMID- 8461673 TI - The politics of poverty and health. PMID- 8461674 TI - Tomlinson report. PMID- 8461675 TI - Tomlinson report. PMID- 8461676 TI - Cardiotocography during labour. PMID- 8461677 TI - Mothering skills of women with mental illness. PMID- 8461678 TI - Screening newborn infants for Duchenne muscular dystrophy. PMID- 8461679 TI - The Clintons go to Washington: a healthy move? PMID- 8461680 TI - Experience with screening newborns for Duchenne muscular dystrophy in Wales. AB - OBJECTIVES: To assess the acceptability of screening newborn boys for Duchenne muscular dystrophy. DESIGN: Screening is offered on the basis of informed consent in response to an information sheet entitled "A new test for baby boys--Do you want it?" The programme includes a prospective long term evaluation of family responses to early diagnosis and a comparison of their experiences and perceptions with those families who have undergone the later traditional clinical diagnosis. SETTING: All maternity units throughout Wales. Samples obtained through screening programme for phenylketonuria and congenital hypothyroidism. SUBJECTS: Those families whose son had a positive screening test. MAIN OUTCOME MEASURES: Creatine kinase activity. Venous blood test to confirm positive result. Molecular genetic mutation analysis. Muscle biopsy and dystrophin analysis. Qualitative measure of satisfaction among affected families. RESULTS: 34,219 Boys have been screened and nine affected families have been identified. Eight families were very positive about the programme. Three chose not to complete the diagnostic process. CONCLUSION: The programme should continue to permit a full evaluation of the issues involved and should serve as a model for other initiatives within the community for genetic disease. PMID- 8461681 TI - Explaining socioeconomic differences in sickness absence: the Whitehall II Study. AB - OBJECTIVE: To describe and explain the socioeconomic gradient in sickness absence. DESIGN: Analysis of questionnaire and sickness absence data collected from the first phase of the Whitehall II study. Grade of employment was used as a measure of socioeconomic status. SETTING: 20 civil service departments in London. SUBJECTS: 6900 male and 3414 female civil servants aged 35-55 years. MAIN OUTCOME MEASURES: Rates of short spells (< or = 7 days) and long spells (> 7 days) of sickness absence. RESULTS: A strong inverse relation between grade of employment and sickness absence was evident. Men in the lowest grade had rates of short and long spells of absence 6.1 (95% confidence interval 5.3 to 6.9) and 6.1 (4.8 to 7.9) times higher than those in the highest grade. For women the corresponding rate ratios were 3.0 (2.3 to 3.9) and 4.2 (2.5 to 6.8) respectively. Several risk factors were identified, including health related behaviours (smoking and frequent alcohol consumption), work characteristics (low levels of control, variety and use of skills, work pace, and support at work), low levels of job satisfaction, and adverse social circumstances outside work (financial difficulties and negative support). These risk factors accounted for about one third of the grade differences in sickness absence. CONCLUSION: Large grade differences in sickness absence parallel socioeconomic differences in morbidity and mortality found in other studies. Identified risk factors accounted for a small proportion of the grade differences in sickness absence. More accurate measurement of the risk factors may explain some of the remaining differences in sickness absence but other factors, as yet unrecognised, are likely to be important. PMID- 8461683 TI - Clinical symptoms associated with seroconversion for HIV-1 among misusers of intravenous drugs: comparison with homosexual seroconverters and infected and non infected intravenous drug misusers. AB - OBJECTIVE: To study the clinical symptoms associated with seroconversion for HIV 1 among misusers of intravenous drugs. DESIGN: Case-control study in cohorts of drug misusers and homosexual men. SETTING: Outpatient clinic, Municipal Health Service, Amsterdam. SUBJECTS: Misusers of intravenous drugs from our prospective cohort who seroconverted for HIV. Controls were drug users positive for HIV, drug users negative for HIV, and homosexual men who had seroconverted. RESULTS: Five out of 18 (28%) drug users were admitted to hospital with bacterial pneumonia in the four to six months between their last visit at which they were HIV negative and their first visit when they were HIV positive. For comparison none of the 27 homosexual men who seroconverted for HIV, three out of 177 (2%) drug users negative for HIV, and 10 out of 112 (9%) drug users positive for HIV reported bacterial pneumonia. One out of the 18 drug users who seroconverted suffered from oesophageal candidiasis at the time of seroconversion. Other clinical symptoms did not differ between drug users who seroconverted and those who remained negative for HIV, probably due to the high background morbidity among the drug users. CONCLUSIONS: Seroconversion to HIV-1 among intravenous drug misusers is associated with bacterial pneumonia. Those drug users with previously negative test results for HIV who are admitted to hospital for bacterial pneumonia should be tested to detect primary infection with HIV-1. PMID- 8461682 TI - Vitamin A supplementation in infectious diseases: a meta-analysis. AB - OBJECTIVE: To study the effect of vitamin A supplementation on morbidity and mortality from infectious disease. DESIGN: A meta-analysis aimed at identifying and combining mortality and morbidity data from all randomised controlled trials of vitamin A. RESULTS: Of 20 controlled trials identified, 12 trials were randomised trials and provided "intention to treat" data: six community trials in developing countries, three in children admitted to hospital with measles, and three in very low birth weight infants. Combined results for community studies suggest a reduction of 30% (95% confidence interval 21% to 38%; two tailed p < 0.0000001) in all cause mortality. Analysis of cause specific mortality showed a reduction in deaths from diarrhoeal disease (in community studies) by 39% (24% to 50%; two tailed p < 0.00001); from respiratory disease (in measles studies) by 70% (15% to 90%; two tailed p = 0.02); and from other causes of death (in community studies) by 34% (15% to 48%; two tailed p = 0.001). Reductions in morbidity were consistent with the findings for mortality, but fewer data were available. CONCLUSIONS: Adequate supply of vitamin A, either through supplementation or adequate diet, has a major role in preventing morbidity and mortality in children in developing countries. In developed countries vitamin A may also have a role in those with life threatening infections such as measles and those who may have a relative deficiency, such as premature infants. PMID- 8461684 TI - Alcohol and cor pulmonale in chronic bronchitis and emphysema. PMID- 8461685 TI - Fundholding in northern region: the first year. AB - OBJECTIVE: To describe the experiences of 10 fundholding practices in the Northern region during 1991-2 and to elicit subjective assessments of the impact of their change in status on practice management and patient care. DESIGN: Semistructured interviews were conducted with clinicians and practice managers; other staff in the practices were asked to fill in questionnaires. Questions were asked about the preparatory year, the impact of fundholding on clinical practice and practice management, perceptions of the costs and benefits of fundholding, and views about the future of the scheme. SETTING: 10 of the 28 first wave fundholding practices in the Northern region, March-July 1992. RESULTS: Two interviews were conducted in nine practices and one interview in the tenth practice. Replies to the questionnaire were received from 35 general practitioners (73%) and 89 (58%) nonmedical staff. Practices sought independence in applying for fundholding status and found the preparatory year challenging and time consuming. General practitioners thought that the greatest change had occurred in relationships with consultants and the least change in relationships with patients. Most respondents thought that fundholding had changed the way they worked. The perceived benefits of fundholding were mentioned more often than the perceived costs. CONCLUSIONS: The results offer some encouragement to the proponents of fundholding, but more longitudinal studies are needed to evaluate the misgivings of critics of the scheme. Fundholders are uncertain about their ability to make savings year after year, particularly in an increasingly cost contained environment. PMID- 8461686 TI - "Not clinically indicated": patients' interests or resource allocation? AB - The decision that a particular intervention is not clinically indicated may conceal two quite different ethical assumptions. The first assumption is that the intervention is not of overall benefit to this patient. The second is that limited resources should not be used for this patient. These issues are discussed with reference to cardiac surgery in elderly patients with reference to the main theories of allocation: QALYs, needs theories, the sanctity of life theory, the lottery theory, and market forces. PMID- 8461687 TI - Public health medicine and purchasing health care. PMID- 8461688 TI - ABC of sleep disorders. Function of sleep. PMID- 8461689 TI - Toxic shock syndrome after elective minor dermatological surgery. PMID- 8461690 TI - Counselling in general practice. PMID- 8461691 TI - Counselling in general practice. PMID- 8461692 TI - Monitoring treatment with aminoglycoside antibiotics. PMID- 8461693 TI - Monitoring treatment with aminoglycoside antibiotics. PMID- 8461694 TI - Monitoring treatment with aminoglycoside antibiotics. PMID- 8461695 TI - Monitoring treatment with aminoglycoside antibiotics. PMID- 8461696 TI - Another African disaster. PMID- 8461697 TI - Another African disaster. PMID- 8461698 TI - Electroacupuncture in fibromyalgia. PMID- 8461699 TI - HIV transmission, travel, and Thailand. PMID- 8461700 TI - National standard for entry into general practice. PMID- 8461701 TI - Risk stratification for open heart surgery. PMID- 8461702 TI - Laser treatment of port wine stains. PMID- 8461703 TI - Cardiovascular disease in developing countries. PMID- 8461704 TI - Rationing. PMID- 8461705 TI - Working with adult survivors of child sexual abuse. PMID- 8461706 TI - Bronchospasm during disulfiram-ethanol test reaction. PMID- 8461707 TI - Monitoring cyclosporin treatment. PMID- 8461708 TI - Working with adult survivors of child sexual abuse. PMID- 8461709 TI - Community care. PMID- 8461710 TI - Condyloma acuminatum and squamous papilloma of the palate. PMID- 8461711 TI - Contracting arrangements. PMID- 8461712 TI - Community care. PMID- 8461713 TI - Consultant episodes. PMID- 8461714 TI - Junior doctors' hours. PMID- 8461715 TI - Junior doctors' hours. PMID- 8461716 TI - Waiting times for outpatient appointments. PMID- 8461717 TI - Screening for hypertrophic cardiomyopathy. PMID- 8461718 TI - On not listening to patients. PMID- 8461719 TI - Antibiotic prophylaxis of neonatal group B streptococcal infections. PMID- 8461720 TI - Richard Doll at 80. PMID- 8461721 TI - Trends in incidence of anal cancer in Denmark. AB - OBJECTIVE: To study long term trends in incidence of anal cancer in a well monitored, unselected population. DESIGN: Descriptive epidemiological study based on data from the Danish Cancer Registry. SETTING: Denmark, 1943-87. MAIN OUTCOME MEASURES: Time related changes in anal cancer incidence according to sex, age, birth cohort, urban or rural residence, and marital status. RESULTS: The incidence of anal cancer remained fairly constant in the period 1943-57 and was similar for men and women, but it increased 1.5-fold among men and nearly tripled among women thereafter. Among men the incidence increased from 0.25 per 100,000 population (world standardised) in 1958-62 to 0.38 in 1983-7 (p = 0.01) and among women from 0.28 to 0.74 (p < 0.01). The greatest increase was among residents of the capital (Copenhagen). During 1943-87 age specific trends increased in young and middle aged men and in all age groups among women. Men with anal cancer were significantly more likely throughout the study period to be unmarried than were patients with cancer of the colon (adjusted odds ratio 2.7; 95% confidence interval 2.0 to 3.6) and stomach (2.1; 1.5 to 2.8), but no association with marital status was found among women. CONCLUSIONS: The distribution and incidence of anal cancer have changed appreciably since around 1960, especially among women, which indicates important aetiological changes. Changes in sexual behaviour may have facilitated the spread of a transmittable agent of aetiological importance. It has recently been suggested that cigarette smoking promotes anal cancer, and this finds indirect support in the synchronism between changes in anal cancer incidence and heavy smoking behaviour. Factors associated with homosexuality are likely to explain some of the cases among men. PMID- 8461722 TI - The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. AB - OBJECTIVE: To determine how fetal growth is related to death from cardiovascular disease in adult life. DESIGN: A follow up study of men born during 1907-24 whose birth weights, head circumferences, and other body measurements were recorded at birth. SETTING: Sheffield, England. SUBJECTS: 1586 Men born in the Jessop Hospital. MAIN OUTCOME MEASURE: Death from cardiovascular disease. RESULTS: Standardised mortality ratios for cardiovascular disease fell from 119 in men who weighed 5.5 pounds (2495 g) or less at birth to 74 in men who weighed more than 8.5 pounds (3856 g). The fall was significant for premature cardiovascular deaths up to 65 years of age (chi 2 = 5.0, p = 0.02). Standardised mortality ratios also fell with increasing head circumference (chi 2 = 4.6, p = 0.03) and increasing ponderal index (weight/length3) (chi 2 = 3.8, p = 0.05; for premature deaths chi 2 = 6.0, p = 0.01). They were not related to the duration of gestation. Among men for whom the ratio of placental weight to birth weight was in the highest fifths the standardised mortality ratio was 137. CONCLUSION: These findings show that reduced fetal growth is followed by increased mortality from cardiovascular disease. They suggest that reduction in growth begins early in gestation. They are further evidence that cardiovascular disease originates through programming of the body's structure, physiology, and metabolism by the environment during fetal life. Maternal nutrition may have an important influence on programming. PMID- 8461723 TI - Sexually transmitted diseases and HIV-1 infection among homosexual men in England and Wales. AB - OBJECTIVE: To examine surveillance data for evidence of changing sexual behaviour and continuing transmission of HIV-1 among men who have sex with men. DESIGN: Analytic study of surveillance data on sexually transmitted diseases. SETTING: England and Wales. MAIN OUTCOME MEASURES: Number of cases of rectal gonorrhoea and newly diagnosed HIV infection in homosexual men. RESULTS: New cases of gonorrhoea among men attending genitourinary medicine clinics increased by 7.7% in 1989 and by 4.2% in 1990. Reports of rectal isolates of Neisseria gonorrhoeae also rose and the male to female ratio for patients with rectal gonorrhoea changed from 0.3:1 during 1988-9 to 2.6:1 in 1990-1. Although the overall number of cases of acute hepatitis B fell during 1988-91, 81 and 82 homosexual men were infected in 1990 and 1991 respectively compared with 50 and 42 in 1988 and 1989. 1526 men had HIV-1 infection diagnosed in 1991, the largest number since 1987. Twenty eight of the 97 (29%) men who seroconverted between January 1989 and December 1991 were aged less than 25. The proportion of men aged 15-19 who were found to be infected with HIV-1 at their first test increased from an average of 2.4% up to 1990 to 4.7% in the first nine months of 1991. The prevalence of HIV infection in men under 25 attending genitourinary medicine clinics in London was 17% compared with 7.8% outside London. CONCLUSION: Unsafe sexual behaviour and HIV transmissions have increased among homosexual men after a period of decline. Recent HIV transmissions may disproportionately affect younger men. PMID- 8461724 TI - Dangers of long waiting times for outpatient appointments at a urology clinic. PMID- 8461725 TI - Effect of long term tamoxifen treatment on bone turnover in women with breast cancer. PMID- 8461726 TI - Prevalence of symptoms in patients with simple renal cysts. PMID- 8461727 TI - Analysis of national register of Down's syndrome in England and Wales: trends in prenatal diagnosis, 1989-91. PMID- 8461728 TI - Effect of NHS reforms on general practitioners' referral patterns. AB - OBJECTIVE: To compare outpatient referral patterns in fundholding and non fundholding practices before and after the implementation of the NHS reforms in April 1991. DESIGN: Prospective collection of data on general practitioners' referrals to specialist outpatient clinics between June 1990 and March 1992 and detailed comparison of two time periods: October 1990 to March 1991 (phase 1) and October 1991 to March 1992 (phase 2). SETTING: 10 fundholding practices and six non-fundholding practices in the Oxford region. SUBJECTS: Patients referred to consultant outpatient clinics. RESULTS: After implementation of the NHS reforms there was no change in the proportion of referrals from the two groups of practices which crossed district boundaries. Both groups of practices increased their referral rates in phase 2 of the study, the fundholders from 107.3 per 1000 patients per annum (95% confidence interval 106 to 109) to 111.4 (110 to 113) and the non-fundholders from 95.0 (93 to 97) to 112.0 (110 to 114). In phase 2 there was no difference in overall standardised referral rates between fundholders and non-fundholders. Just over 20% of referrals went to private clinics in phase 1. By phase 2 this proportion had reduced by 2.2% (1.0% to 3.4%) among the fundholders and by 2.7% (1.2% to 4.2%) among the non-fundholders. CONCLUSIONS: Referral patterns among fundholders and non-fundholders were strikingly similar after the implementation of the NHS reforms. There was no evidence that fundholding was encouraging a shift from specialist to general practice care or that budgetary pressures were affecting general practitioners' referral behaviour. PMID- 8461730 TI - Letter from Albania. A country in transition. PMID- 8461729 TI - Screen detected high blood pressure under 40: a general practice population followed up for 21 years. AB - OBJECTIVE: To assess hypertension detected under 40 in a general practice population. DESIGN: Prospective case-control study. SETTING AND SUBJECTS: Former coal mining community in south Wales. Systematic case finding for hypertension and associated risk factors applied to a mean total population of 1945 from age 20 on a five year cycle through 21 years. Mean population aged 20-39, 227 men and 213 women. Case criteria: age < 40 and mean systolic pressure > or = 160 mm Hg or diastolic pressure > or = 100 mm Hg. Age and sex matched controls randomly sampled from the same population. MAIN OUTCOME MEASURES: Mean initial pressures and pressures at follow up in 1989 or preceding death, and all cardiovascular events. RESULTS: 25 men and 16 women met criteria. Estimated five yearly inceptions were 26/1000 for men and 18/1000 for women. Male group mean initial blood pressure was 164/110 mm Hg for cases, falling to 148/89 mm Hg at follow up. Five male cases died at mean age 47.8, compared with two controls at 49.5. Female group mean initial pressure was 172/107 mm Hg for cases, falling to 145/86 mm Hg at follow up. One female case died aged 50, no controls. 10 male cases had non fatal cardiovascular events at mean age 40.2, compared with two controls at mean age 50.5. Four female cases had non-fatal events at mean age 47.2, compared with one control aged 58. Male differences were statistically significant. CONCLUSIONS: Hypertension under 40 is dangerous, commoner in men than women, rarely secondary to classic causes, and may be controlled in general practice on a whole community basis. PMID- 8461731 TI - ABC of sleep disorders. Circadian rhythms. PMID- 8461732 TI - Persistent glue ear in children. PMID- 8461733 TI - Persistent glue ear in children. PMID- 8461734 TI - Persistent glue ear in children. PMID- 8461735 TI - Persistent glue ear in children. PMID- 8461736 TI - Medical education. PMID- 8461737 TI - Medical education. PMID- 8461738 TI - Persistent glue ear in children. PMID- 8461739 TI - Medical education. PMID- 8461740 TI - Monitoring theophylline treatment. PMID- 8461741 TI - Liver failure induced by paracetamol. PMID- 8461742 TI - Monitoring theophylline treatment. PMID- 8461743 TI - Treating mentally ill people in the community. PMID- 8461744 TI - Treating mentally ill people in the community. PMID- 8461745 TI - Treating mentally ill people in the community. PMID- 8461746 TI - Treating mentally ill people in the community. PMID- 8461747 TI - Preoperative autologous blood transfusion programme. PMID- 8461748 TI - Consensus statements. PMID- 8461749 TI - Misuse of anabolic drugs. PMID- 8461750 TI - Oral cancer in Scotland. PMID- 8461751 TI - Saving the normal foreskin. PMID- 8461752 TI - Child resistant containers for liquid medications. PMID- 8461753 TI - Child resistant containers for liquid medications. PMID- 8461754 TI - Computer generated protocols. PMID- 8461755 TI - Managing urinary tract infection. PMID- 8461756 TI - Decreasing quality of semen. PMID- 8461757 TI - Screening for abdominal aortic aneurysms. PMID- 8461759 TI - Dentists and the NHS. PMID- 8461758 TI - Nurse practitioners in accident and emergency departments. PMID- 8461760 TI - Malignant melanomas in general practice. PMID- 8461761 TI - New clinics for HIV testing: a waste of money. PMID- 8461762 TI - ACE inhibitors after myocardial infarction. PMID- 8461763 TI - Deprivation payments. PMID- 8461764 TI - Improving London's health service. PMID- 8461765 TI - Treating bed wetting. PMID- 8461766 TI - Mycobacterium tuberculosis DNA in tissue affected by sarcoidosis. AB - OBJECTIVE: To investigate the prevalence of Mycobacterium tuberculosis DNA in granulomatous tissues from patients with sarcoidosis and from controls matched for age, sex, and tissue by using the polymerase chain reaction. DESIGN: Single blind control trial. SUBJECTS: 16 patients with sarcoidosis who had undergone diagnostic biopsy of lung, skin, or lymph node and 16 patients with squamous cell carcinoma or Hodgkin's disease to act as controls. In addition, four lung specimens infected with M tuberculosis were included as positive controls. RESULTS: M tuberculosis DNA was present in sarcoid tissues containing granulomas from seven of the 16 patients and one of the 16 matched controls. Two of the four specimens known to be infected with M tuberculosis were positive in the controlled experiment. CONCLUSION: These figures suggest that M tuberculosis DNA is detected as readily in patients with sarcoidosis as in patients with frankly tuberculous tissues and imply that M tuberculosis may be linked to the cause of sarcoidosis. PMID- 8461767 TI - Demographic and social characteristics of adults with cystic fibrosis in the United Kingdom. AB - OBJECTIVE: To obtain information about social and demographic characteristics and lifestyle of adult patients with cystic fibrosis, including those who do not attend major specialist clinics. DESIGN: Confidential self completion postal questionnaire to adult patients with cystic fibrosis, asking about social and demographic characteristics, social class and occupation, employment, education, insurance and social security benefits, symptom severity, and medical care. SETTING: National association for adults with cystic fibrosis. SUBJECTS: 1052 adult members of the Association of Cystic Fibrosis Adults UK, accounting for 68% of those with cystic fibrosis in the United Kingdom population over 16 years of age and over 80% of those over 25 in June 1990. RESULTS: The response rate was 82% (397 women, 423 men). Most adults with cystic fibrosis were found to be living fulfilling lives into adulthood. Significantly fewer men were married or cohabiting than women (110 (26%) men, 175 (44%) women). 420 (55%) responders were working, and of these 235 (56%) had less than two weeks' sick leave a year. Half of those not employed gave ill health as the reason. Revealing that they had cystic fibrosis at job interviews reduced likelihood of being employed for those with mild to moderate disease. People with cystic fibrosis had been less successful than the general population in achieving O level or equivalent qualifications, but more successful in achieving A level or higher qualifications. Achievement of any qualifications enhanced employment prospects irrespective of disease severity. CONCLUSION: Contrary to an image of chronic ill health and disability, a high proportion of adults with cystic fibrosis are living full and productive lives. PMID- 8461768 TI - Clinical diagnosis of pyloric stenosis: a declining art. AB - OBJECTIVE: To assess whether diagnostic imaging of pyloric stenosis has made a difference in rapidity of diagnosis, duration of pre-operative hydration, and length of stay in hospital. DESIGN: Chart review of infants with confirmed diagnosis of pyloric stenosis. SETTING: Paediatric teaching hospital. SUBJECTS: 215 infants with a confirmed diagnosis of pyloric stenosis seen during 1974-7 and 187 infants with pyloric stenosis seen during 1988-91. MAIN OUTCOME MEASURES: State of hydration on admission, time between presentation to hospital and a definite diagnosis, techniques used to make the diagnosis, whether a pyloric mass was felt before or after an imaging procedure, time between presentation and surgery, and length of stay in hospital. RESULTS: The average age at presentation was 40 days in both groups. A pyloric mass was palpated either without or before an imaging study in 87% (187/215) of cases during 1974-7 but in only 49% (91/187) during 1988-91. The use of barium meal examination and ultrasonography increased from 20% (42/215) of cases during 1974-7 to 61% (114/187) during 1988-91. There were no significant differences between the two groups in the time taken to establish a diagnosis, the mean duration of preoperative treatment, or the length of stay in hospital (after allowance for the decline in average length of stay of all hospital patients between the two periods). CONCLUSIONS: An increased use of diagnostic imaging for pyloric stenosis did not lead to earlier diagnosis or better management. While imaging is important in identifying pyloric stenosis in difficult cases, increasing reliance on imaging has reduced doctors' skills in diagnosing pyloric stenosis clinically. PMID- 8461769 TI - Antibiotic resistant propionibacteria in acne: need for policies to modify antibiotic usage. PMID- 8461771 TI - Weak link in vaccine cold chain. PMID- 8461770 TI - Knowledge and use of secondary contraception among patients requesting termination of pregnancy. PMID- 8461772 TI - Risk of vertebral fracture in women with rheumatoid arthritis. PMID- 8461773 TI - National asthma attack audit 1991-2. General Practitioners in Asthma Group. AB - OBJECTIVE: To describe the frequency and characteristics of asthma attacks in the United Kingdom and to compare actual management with recommended guidelines for the management of attacks. DESIGN: Correspondence survey. SETTING: 218 general practices in the United Kingdom. SUBJECTS: 1775 patients of all ages who had a total of 1805 asthma attacks over three months. MAIN OUTCOME MEASURES: Patient characteristics, place of management of attacks, comparison of actual management with recommended guidelines. RESULTS: Of the 1805 attacks, 300 occurred in boys aged 0-9, 144 in girls aged 0-9, and 118 in women aged 20-29. The estimated frequency of attacks in the community was 14.3 per 1000 patients per year. 1546 (86%) patients with attacks were managed within general practice, 225 (12%) were admitted to hospital, and 34 (2%) were discharged from an accident and emergency department. Two patients died. On initial presentation, 248 (14%) patients were "not breathless," 900 (50%) were "moderately breathless," 535 (30%) were "breathless and distressed," 68 (4%) were "too breathless to talk," and 2 were "moribund." Recording of clinical data was variable. Underuse of nebulised bronchodilators and systemic steroid was apparent in all grades of clinical severity. Contrary to current guidelines for asthma management, "step up" in maintenance therapy after an attack was often not practised. CONCLUSION: Reported management was at variance with recommended guidelines. This has major implications for the design and distribution of future guidelines. PMID- 8461774 TI - Ethical issues in randomised prevention trials. PMID- 8461775 TI - Newcastle: "if it doesn't work here, it can't work anywhere". PMID- 8461776 TI - Some guidelines on the use of cost effectiveness league tables. AB - Decisions to allocate resources in health care are increasingly influenced by relative cost effectiveness. To warn decision makers of some of the pitfalls currently found in cost effectiveness league tables and to suggest how meaningful comparisons may be made between health care technologies a published league table was scrutinised by examining its sources. This showed some of the methodological problems surrounding such tables and how such difficulties could be reduced in future. The source studies in the table featured different years of origin, discount rates, health state evaluations, settings, and types of comparison programmes; all of these differences may raise problems for meaningful comparison. Decision makers need to assess the relative value for money of competing health care interventions. In the absence of systematic comparisons such assessments are likely to take place informally. This will probably have a worse risk-benefit trade off than the formalized use of league tables. PMID- 8461777 TI - ABC of sleep disorders. Recreational drugs and sleep. PMID- 8461778 TI - Foreign body aspiration: a hazard of metered dose inhalers. PMID- 8461779 TI - Umbilical cord clamping in preterm infants. PMID- 8461780 TI - Umbilical cord clamping in preterm infants. PMID- 8461781 TI - Problem lists in letters. PMID- 8461782 TI - Problem lists in letters. PMID- 8461783 TI - Problem lists in letters. PMID- 8461784 TI - Problem lists in letters. PMID- 8461785 TI - The laryngeal mask. PMID- 8461786 TI - The laryngeal mask. PMID- 8461787 TI - The laryngeal mask. PMID- 8461788 TI - Gestational diabetes mellitus. PMID- 8461789 TI - Gestational diabetes mellitus. PMID- 8461790 TI - Alternative allergy and the GMC. PMID- 8461791 TI - Sexual behaviour. PMID- 8461792 TI - Poor growth in children. PMID- 8461793 TI - Sexual behaviour. PMID- 8461794 TI - Circumcision. PMID- 8461795 TI - Initiation of hypertension in utero. PMID- 8461796 TI - Epidemiology of endometriosis. PMID- 8461797 TI - Hypersensitivity to dexamethasone. PMID- 8461798 TI - Business travel and sexually transmitted diseases. PMID- 8461799 TI - Community dermatology. PMID- 8461800 TI - General practitioners in partnership with management. PMID- 8461801 TI - BMA's evidence on specialist training. PMID- 8461802 TI - Piscatorial epistles. PMID- 8461803 TI - Shanghai declaration on non-communicable diseases. WHO Directors of Non Communicable Disease Collaborating Centres and Key Officials. PMID- 8461804 TI - Paracelsus, and 500 years of encouraging scientific inquiry. PMID- 8461805 TI - Hypertension and cancer. PMID- 8461806 TI - Diabetic care in general practice. PMID- 8461807 TI - Treating hypoglycaemia in general practice. PMID- 8461808 TI - Non-medical use of ketamine. PMID- 8461809 TI - Meeting local needs. PMID- 8461810 TI - Incidence of and mortality from cancer in hypertensive patients. AB - OBJECTIVES: To assess incidence of and mortality from cancer in hypertensive patients taking atenolol, comparing the findings with two control populations and with hypertensive patients taking other drugs. DESIGN: Retrospective analysis of patients first seen in the Glasgow Blood Pressure Clinic between 1972 and 1990. Patients' records were linked with the registrar general's data for information on mortality and with the West of Scotland Cancer Registry for information on incident and fatal cancers. Cancers were compared in patients and controls and in patients taking atenolol, beta blockers other than atenolol, and hypotensive drugs other than beta blockers. SUBJECTS: 6528 male and female patients providing 54,355 years of follow up. SETTING: Hypertension clinic in Glasgow. MAIN OUTCOME MEASURES: Observed numbers of cancers in clinic patients were compared with expected numbers derived from cancer rates in two control populations adjusted for age, sex, and time period of data collection. RESULTS: Cancer mortality was not significantly different in clinic patients as a whole and controls. Incident and fatal cancers were not significantly increased in male or female patients taking atenolol. Cancer incidence did not rise in the clinic after a large increase in prescriptions for atenolol after 1976. CONCLUSION: This analysis does not suggest a link between atenolol and cancer. PMID- 8461811 TI - Case-control study of leukaemia and non-Hodgkin's lymphoma among children aged 0 4 years living in west Berkshire and north Hampshire health districts. AB - OBJECTIVE: To investigate the relation between parental employment in the nuclear industry and childhood leukaemia and non-Hodgkin's lymphoma. DESIGN: Case-control study. SETTING-West Berkshire and Basingstoke and North Hampshire District Health Authorities. SUBJECTS: 54 children aged 0-4 years who had leukaemia or non Hodgkin's lymphoma diagnosed during 1972-89, who were born in the study area and were resident there when cancer was diagnosed. Six controls were selected for each case: four from hospital delivery registers and two from livebirth registers maintained by the NHS central register. Controls were matched for sex, date of birth (within six months), and area of residence at birth and time of diagnosis. MAIN OUTCOME MEASURES: Parents' employment by the nuclear industry and exposure to ionising radiation at work. RESULTS: Five (9%) of the 54 cases and 14 (4%) of the 324 controls had fathers or mothers, or both, who had been employed by the nuclear industry (relative risk 2.2, 95% confidence interval 0.6 to 6.9). Nuclear industry employees who work in areas where exposure to radiation is possible are given film badges to monitor their exposure to external penetrating ionising radiation. Three fathers of cases and two fathers of controls (and no mothers of either) had been monitored in this way before their child was conceived (relative risk 9.0, 95% confidence interval 1.0 to 107.8). No father (of a case or control) had accumulated a recorded dose of more than 5 mSv before his child was conceived, and no father had been monitored at any time in the four years before his child was conceived. A dose-response relation was not evident among fathers who had been monitored. CONCLUSIONS: These results suggest that the children of fathers who had been monitored for exposure to external penetrating ionising radiation in the nuclear industry may be at increased risk of developing leukaemia before their fifth birthday. The finding is based on small numbers and could be due to chance. If the relationship is real the mechanisms are far from clear, except that the effect is unlikely to be due to external radiation; the possibility that it could be due to internal contamination by radioactive substances or some other exposure at work should be pursued. The above average rates of leukaemia in the study area cannot be accounted for by these findings. PMID- 8461812 TI - Comparison of nifedipine and propranolol as second line agent for hypertension in black Kenyans. PMID- 8461813 TI - Cancer mortality and atenolol treatment. PMID- 8461814 TI - Does awareness of rates of obstetric interventions change practice? PMID- 8461815 TI - Prompting the clinical care of non-insulin dependent (type II) diabetic patients in an inner city area: one model of community care. AB - OBJECTIVE: To evaluate the effectiveness and acceptability of centrally organised prompting for coordinating community care of non-insulin dependent diabetic patients. DESIGN: Randomised single centre trial. Patients allocated to prompted care in the community or to continued attendance at hospital diabetic clinic (controls). Median follow up two years. SETTING: Two hospital outpatient clinics, 38 general practices, and 11 optometrists in the catchment area of a district general hospital in Islington. PATIENTS: 181 patients attending hospital outpatient clinics. NULL HYPOTHESIS: There is no difference in process of medical care measures and medical outcome between prompted community care and hospital clinic care. RESULTS: 14 hospital patients failed to receive a single review in the clinic as compared with three patients in the prompted group (chi 2 = 6.1, df = 1; p = 0.013). Follow up for retinal screening was better in prompted patients than in controls; two prompted patients defaulted as against 12 controls (chi 2 = 6.9, df = 1; p = 0.008). Three measures per patient yearly were more frequent in prompted patients: tests for albuminuria (median 3.0 v 2.3; p = 0.03), plasma glucose estimations (3.1 v 2.5; p = 0.003), and glycated haemoglobin estimations (2.4 v 0.9; p < 0.001). Continuity of care was better in the prompted group (3.2 v 2.2 reviews by each doctor seen; p < 0.001). The study ended with no significant differences between the groups in last recorded random plasma glucose concentration, glycated haemoglobin value, numbers admitted to hospital for a diabetes related reason, and number of deaths. Questionnaires revealed a high level of patient, general practitioner, and optometrist satisfaction. CONCLUSIONS: Six monthly prompting of non-insulin treated diabetic patients for care by inner city general practitioners and by optometrists is effective and acceptable. PMID- 8461817 TI - Community care and the fundholder. AB - According to the government, clearly agreed local arrangements should enable individual general practitioners to make their full contribution to the new system of community care without getting involved in extra bureaucracy. From 1 April the main part of that contribution will be to refer to social services those patients who seem to need social care. Many general practitioners are worried that such referrals will be complex and time consuming and will generate too much extra work. Moreover, general practitioners may also be asked to see patients specifically to help social workers' assessment procedures, and many fear that such consultations will overwork and underpay them. General practitioner fundholders already use contracts to spell out what they expect from hospital services. From 1 April they will be able to set up contracts for community health services such as district nursing and chiropody, and possibly this might be extended to social aspects of community care. Over the past 14 months Dr Rhidian Morris and his partners in a fundholding practice in Devon have piloted contracts for all aspects of community care. In this article Dr Morris explains how the most radical part of the pilot project--the contract for social care--was set up. He argues that the lessons on communication that came from what was essentially a fundholding project could apply also to non-fundholding practices. PMID- 8461818 TI - The fortysomething barrier: medicine and age discrimination. AB - Agism in the medical profession is mainly covert but it is not uncommon. It is widely believed that people become less productive as they get older. However, research has shown that older people have less absenteeism, more job stability, and greater output than younger workers. Job losses, which until recently were unheard of in the NHS, usually affect older people first, resulting in the loss of those with the most skill and experience. With an aging population it is important that the government takes steps to discourage age discrimination in the NHS and Britain as a whole. PMID- 8461816 TI - Influences on control in diabetes mellitus: patient, doctor, practice, or delivery of care? AB - OBJECTIVE: To assess patient, doctor, practice, and process of care variables for their effect on glycaemic control in diabetes mellitus, and to quantify their relative effects. DESIGN: Search of general practice medical records, patient questionnaires and examination, doctor questionnaire, videotaping and analysis of consultations, and practice questionnaire. SETTING: 12 practices with 32 participating general practitioners in Nottinghamshire. SUBJECTS: 318 patients randomly selected from those with diabetes in each practice, 10 for each participating doctor. MAIN OUTCOME MEASURE: Glycaemic control as measured by random glycated haemoglobin A1c estimation (random haemoglobin A1 measurement). RESULTS: Glycaemic control was significantly related to the disease process as measured by years since diagnosis, treatment group, and number of diabetes related clinical events. Females had significantly worse control than males. Other patient factors, such as age, social class, lifestyle, attitudes, satisfaction, and knowledge, had no association with glycaemic control. Of all the doctor factors examined, only doctors who professed a special interest in diabetes achieved significantly better glycaemic control. Bigger and better equipped practices and those with a diabetic miniclinic had patients with significantly better glycaemic control, as did those with access to dietetic advice. Patients attending hospital clinics had worse glycaemic control, but this seemed to be attributable to the case mix and practice characteristics. Shared care did not contribute to the multiple linear regression model. CONCLUSION: Glycaemic control among diabetic patients in the community is related to such factors as treatment group, sex, and years since diagnosis; it is also related to the organisation and process of care. The findings support concentrating diabetic care on partners with special interests in diabetes in well equipped practices with adequate dietetic support. PMID- 8461819 TI - ABC of sleep disorders. Sleep disorders in children. PMID- 8461820 TI - Late presentation of traumatic rupture of the diaphragm in a child. PMID- 8461821 TI - How many doctors does Britain need? PMID- 8461822 TI - How many doctors does Britain need? PMID- 8461823 TI - Unlicensed nicotine skin patches. PMID- 8461824 TI - How many doctors does Britain need? PMID- 8461825 TI - Medical education. PMID- 8461826 TI - Death from cancer at home. PMID- 8461827 TI - Death from cancer at home. PMID- 8461828 TI - Long term care of elderly people in the NHS. PMID- 8461829 TI - Respite care. PMID- 8461830 TI - Children of parents infected with HIV in Lothian. PMID- 8461831 TI - Retinoblastoma in children of former residents of Seascale. PMID- 8461832 TI - Persistent glue ear in children. PMID- 8461833 TI - Inheritance of chronic inflammatory bowel disease. PMID- 8461834 TI - Pre-emptive analgesia. PMID- 8461835 TI - BCG vaccination and health care workers. PMID- 8461836 TI - Selective decontamination of the gut. PMID- 8461837 TI - Toxic shock syndrome after minor surgery. PMID- 8461838 TI - Risks to surgeons and patients from HIV and hepatitis. PMID- 8461839 TI - Gloves for venepuncture. PMID- 8461840 TI - Microalbuminuria, height, and sex. PMID- 8461841 TI - Police surgeons. PMID- 8461842 TI - Low blood pressure and wellbeing. PMID- 8461843 TI - The cervical spine in rheumatoid arthritis. PMID- 8461844 TI - Gangliosides in neurological diseases. PMID- 8461845 TI - Patients' interests or resource allocation? PMID- 8461846 TI - NHS reforms. PMID- 8461847 TI - Tipping the balance. PMID- 8461848 TI - Waiting times for outpatient appointments. PMID- 8461849 TI - Volatile substances and the law. PMID- 8461850 TI - Brief interventions for alcohol problems: a review. AB - Relatively brief interventions have consistently been found to be effective in reducing alcohol consumption or achieving treatment referral of problem drinkers. To date, the literature includes at least a dozen randomized trials of brief referral or retention procedures, and 32 controlled studies of brief interventions targeting drinking behavior, enrolling over 6000 problem drinkers in both health care and treatment settings across 14 nations. These studies indicate that brief interventions are more effective than no counseling, and often as effective as more extensive treatment. The outcome literature is reviewed, and common motivational elements of effective brief interventions are described. There is encouraging evidence that the course of harmful alcohol use can be effectively altered by well-designed intervention strategies which are feasible within relatively brief-contact contexts such as primary health care settings and employee assistance programs. Implications for future research and practice are considered. PMID- 8461851 TI - Cross system agreement for substance use disorders: DSM-III-R, DSM-IV and ICD-10. AB - This report presents results of a field trial of Substance Use Disorders as defined by DSM-III-R, DSM-IV (proposed) and ICD-10. Diagnoses based on the three systems were derived from interviews using the Composite International Diagnostic Interview (CIDI) in a heterogeneous sample of 521 adults drawn from clinical and community settings. Two issues are addressed: (1) cross system agreement; and (2) syndrome coherence of proposed criterion sets for Substance Dependence in each of the three systems. Findings were as follows: (1) Cross system agreement for Dependence was generally high, especially between DSM-III-R and DSM-IV. (2) Cross system agreement was lower for DSM-III-R and DSM-IV Abuse and very low for DSM-IV Abuse and ICD-10 Harmful Use. (3) Agreement varied across drug categories with lowest DSM-III-R/DSM-IV agreement for alcohol abuse and DSM-IV/ICD-10 agreement for marijuana use disorders. (4) Overall prevalence differed for the three systems with DSM-IV yielding highest rates followed by DSM-III-R and ICD-10 in that order. (5) Factor analysis of Dependence criteria showed high loadings of all items on a single factor across the three diagnostic systems and for all categories of drugs. Implications for validity of the dependence syndrome construct and for revisions in DSM-IV are discussed. PMID- 8461852 TI - Alcohol consumption and related problems among primary health care patients: WHO collaborative project on early detection of persons with harmful alcohol consumption--I. AB - This WHO collaborative project is the first phase of a programme of work aimed at developing techniques for early identification and treatment of persons with hazardous and harmful alcohol consumption. The aim of the present study was to determine the prevalence of hazardous and harmful alcohol use among patients attending primary health care facilities in several countries, and to examine the correlates of drinking behaviour and alcohol-related problems in these culturally diverse populations. The broader purpose was to determine whether there was justification for developing alcohol screening instruments for cross-national use. One thousand, eight hundred and eighty-eight subjects in Australia, Bulgaria, Kenya, Mexico, Norway and the USA underwent a comprehensive assessment of their medical history, alcohol intake, drinking practices, and any physical or psychosocial problems related to alcohol. After non-drinkers and known alcoholics had been excluded, 18% of subjects had a hazardous level of alcohol intake and 23% had experienced at least one alcohol-related problem in the previous year. Intrascale reliability coefficients were uniformly high for the drinking behaviour (dependence) and adverse psychological reactions scales, and moderately high for the alcohol-related problems scales. There were strong correlations between the various alcohol-specific scales, and between these scales and measures of alcohol intake. Although the prevalence of hazardous and harmful alcohol consumption varied from country to country, there was a high degree of commonality in the structure and correlates of drinking behaviour and alcohol related problems. These findings strengthen the case for developing international screening instruments for hazardous and harmful alcohol consumption. PMID- 8461853 TI - The Alcohol Use Disorders Identification Test (AUDIT) in a routine health examination of long-term unemployed. AB - A representative sample of 310 long-term unemployed in Norway was followed for 2 years with clinical examinations and the AUDIT questionnaire. 30% of the men and 8% of the women scored over the cut-off point for an alcohol use disorder. This gives a probable prevalence of 16%. The test predicted return to employment in this sample. The AUDIT answers were also used as a basis for dividing into three groups: 'normal', 'hazardous' and 'harmful'. At 2 year follow-up, 27% had changed group, 32 respondents to the worse and 24 to the better. This 'unstable' group was characterized by weaker social network and more frequent drinking. The AUDIT was judged as a useful instrument both in a routine health examination and as an epidemiological tool. PMID- 8461854 TI - Alcohol consumption and sickness absence: from the Whitehall II study. AB - Previous studies suggest that problem drinkers have markedly increased sickness absence. However, it is not clear how more moderate alcohol consumption and abstinence relate to sickness absence. As part of the Whitehall II study the relationship between different drinking patterns and sickness absence is examined. A total of 10,314 male and female civil servants completed a baseline questionnaire about their drinking habits--the amount of alcohol consumed over the past 7 days and the frequency of drinking over the past 12 months. All sickness absence has been recorded prospectively. Drinking patterns and sickness absence are examined for short spells (< or = 7 days) and long spells (> 7 days) adjusting for other causes of sickness absence: age, grade of employment, smoking, work characteristics and baseline health. Alcohol consumption was strongly related to employment grade, the lower the grade the higher proportion of men and women reporting no alcohol consumption. For men the relation of alcohol intake to short spells of sickness absence (< or = 7 days) appeared to be U-shaped, for long spells (> 7 days) increased rates of absence were found only in frequent drinkers. There was no clear relationship for women, however higher rates of sickness absence were found in non-drinkers. PMID- 8461855 TI - ADH and ALDH genotype profiles in Caucasians with alcohol-related problems and controls. AB - Eighty-two Caucasian patients receiving treatment for alcohol-related problems and eighty four controls were DNA typed for variants in the alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2) gene loci. No association was observed between individual, or combined gene frequencies and the presence of alcohol-related problems. PMID- 8461856 TI - Reduced alcohol use in pregnancy and changed attitudes in the population. AB - The objectives of this study were to investigate (1) changes in consumption of alcohol among pregnant women over a period of 5 years (1984/85-1990), (2) changes of attitudes towards drinking during pregnancy in the general population over the same period of time, and (3) possible connections between (1) and (2). The investigation was designed as a cross-sectional study. Our subjects were two representative samples of pregnant women in Oslo, n = 377 and 425, and two representative samples of the Norwegian population, n = 1004 and 1204. The main outcome measures were a self-completed questionnaire for the pregnant women and a personal interview for the general population sample. There was a significant reduction (50% decrease) in alcohol consumption among the second cohort of pregnant women compared with the first. Furthermore, we found an increase during the 5-year period in the number of persons with a restrictive attitude towards alcohol use during pregnancy. There seems to be a connection between these two phenomena, but with our present state of knowledge it is hard to say anything about the causal relationship between them. PMID- 8461857 TI - Criminal involvement of cocaine users enrolled in a methadone treatment program. AB - This was a study of criminal activities of cocaine users versus non-users enrolled in a methadone treatment program in New York City. Of those 140 methadone clients studied, 100 (71%) were cocaine users. There were no demographic differences between the two groups except marital status. Married clients (including common-law married) were more likely than never-married single clients to be non-users. Cocaine users were significantly more depressed, using the subscale of the Symptom Checklist-90. Although numbers of lifetime arrests and criminal involvement (in the year immediately preceding the research interview) of cocaine non-users were distinctively lower than those of users, the differences were not significant. In a multiple regression analysis, length of stay in the methadone program was the strongest predictor of criminal involvement. Those who were retained longer in the treatment were significantly less likely to be involved in criminal activities, regardless of cocaine use. PMID- 8461858 TI - ICD-10 harmful use of alcohol and the alcohol dependence syndrome: prevalence and implications. AB - Data from a 1988 survey on United States drinking practices and related problems was used to derive the prevalence and population estimates of harmful use of alcohol and the alcohol dependence syndrome as defined in the ICD-10 Clinical Descriptions and Diagnostic Guidelines Version (ICD-10-CDDG). Corresponding estimates were also presented for ICD-10-CDDG diagnoses that incorporated the duration criterion of the ICD-10-Diagnostic Criteria for Research Version (ICD-10 DCR). The prevalence of ICD-10 harmful use and dependence combined, with and without the duration criterion, were 5.2% and 7.1%, respectively. Corresponding harmful use rates were negligible (0.27%). Implications of the extremely low prevalence of harmful use in the US population and the impact of the duration criterion on the rates are discussed in terms of the fundamental nature of alcohol use disorders as syndromes and the viability of the harmful use of alcohol category as originally conceptualized. PMID- 8461859 TI - Liaison services for pregnant drug users. PMID- 8461860 TI - Temazepam abuse. PMID- 8461861 TI - Gender and colorectal cancer. AB - Studies of gender differences in colorectal cancer have shown temporal shifts in incidence and site distribution which can be attributed, in part, to environmental and behavioural factors. In high-risk populations, rectal cancer and left-sided colon cancer have been more frequent in older men, whereas right sided colon cancer has been more commonly found in older women. Among known associations with reduced colorectal cancer risk, women appear to ingest more dietary fibre, seem to benefit more from physical activity and body mass, and consume less alcohol. Although these differences may contribute to the risk differential, hormonal events during reproductive years also appear to affect women's risk at older age. The interactions of sex hormone metabolism and nutrition, including dietary fibre, in colorectal carcinogenesis provide a rewarding field for investigation. PMID- 8461862 TI - Action plan for a tobacco-free Europe: implementation in central and eastern Europe, 1993-94. WHO Regional Office for Europe. AB - Major political and social changes in central and eastern European (CEE) countries offer new opportunities and challenges in tobacco control. Action against tobacco in CEE countries is part of an overall European strategy, the action plan for a tobacco-free Europe. Several CEE countries have voiced their concern about the deterioration of tobacco control and about the entry of the international tobacco industry. In response, the Regional Office has set up a framework for an international task force. The core of the task force consists of the EURO staff and a special consultant. Several European countries and organizations have already expressed their willingness to joint the task force by seconding an expert to participate in the country missions and consensus conferences. This paper describes particular steps to implement the action plan in central and eastern Europe. It outlines priority action to be carried out by the CEE countries themselves and describes possibilities for assistance by all European countries. A key role is assigned to a European alliance on tobacco or health to create psychological and material prerequisites for action as well as act in an advisory role. Some of the projects are already underway, but they can be considerably strengthened by extra resources and support. Some of the projects are possible only with new resources. The project proposals are classified according to the six areas of the new action plan but presented in a different order. This paper sets out a range of activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461863 TI - Adult mortality from leading sites of cancer in Italy and a note on European data. AB - An overview is given of recent patterns of trends in cancer mortality in various age groups in Italy and, for comparative purposes, in other European countries. Important changes in mortality for several major cancer sites have been observed over the last two decades, such as the declines in gastric cancer or the increases in lung cancer mortality. These are difficult to understand and justify from an epidemiological and public health viewpoint, since the main cause of lung cancer (cigarette smoking) has long been known, while the determinants of stomach cancer are still largely undefined. Changes were minor, and inconsistent across countries, for other major cancers, such as intestines or breast. Furthermore, trends were systematically more favourable in young adults (and, to a less extent middle age), as compared to the elderly. The decline in young adults reflects more favourable exposure to risk factors (eg declined smoking prevalence, better diet), but also improvements in diagnostic and therapeutic procedures for some cancers. Due caution is required in any extrapolation, particularly since the distribution of the most common types of cancer changes in subsequent age groups. These favourable trends in young adults offer, none the less, important (and positive) indications as to the likely future trends when the same generations will reach middle and older age. PMID- 8461864 TI - Dietary and other environmental risk factors in acute leukaemias: a case-control study of 119 patients. AB - Selected dietary risk factors and other environmental factors were studied in 119 adult patients (60 males and 59 females of the Cracow region) with acute leukaemia (91 acute myeloid leukaemia and 28 acute lymphoblastic leukaemia), by a case-control study method and logistic regression modelling of the risk of leukaemia. It was shown that the diet of patients with acute leukaemias before the onset of the disease differed qualitatively and quantitatively from that of healthy subjects of control groups. The risk of acute leukaemia was elevated in the subjects characterized by rare consumption of raw vegetables, frequent drinking of milk, frequent consumption of poultry, and drinking of soft water. Other environmental conditions connected with the dietary risk were: frequent viral infections, vaccination with the vaccinia virus, frequent use of aminophenazone, presence of fungi in the house, drinking of milk supplied from own's own cows, and frequent deaths of reared poultry. PMID- 8461865 TI - Oral contraceptive use and risk of benign breast disease in a French case-control study of young women. AB - We report the results of a French hospital-based case-control study designed to analyse the relation between the use of oral contraceptives (OC) and the risk of benign breast disease (BBD). The cases were 286 women, each less than 46 years old, with BBD histologically verified between 1982 and 1985. Controls were 382 patients, matched to cases on year of birth and month of interview, and who were hospitalized for a non-malignant disease other than BBD. Odds ratios were estimated by multivariate regression, taking into account level of education, place of residence, family history of breast cancer, age at menarche, number of children, age at first full-term pregnancy and Quetelet index. The risk of BBD was found to decrease significantly with a longer use of OC before the first full term pregnancy (FFTP), but there was no association between the risk of BBD and the duration of OC use after FFTP. OC use before FFTP reduced the risk of non proliferative disease, but did not significantly affect the risk of proliferative disease. These results did not depend on the amount of oestrogen (0.05 mg or more vs < 0.05 mg) contained in OC. PMID- 8461866 TI - Biliary bile acids in cholelithiasis and carcinoma of the gall bladder. AB - The role of biliary deoxycholate as an endogenous carcinogen and the possible association between cholelithiasis and the subsequent development of carcinoma of the gall bladder is unclear. This paper describes biliary bile acid analysis performed on three groups of patients, 10 with cholelithiasis, 10 with carcinoma of the gall bladder and 10 control patients. This is the first report of bile acid changes in carcinoma of the gall bladder. In these 30 patients the total bile acids concentration was highly variable (11.44-53.68 mg/ml). The mean ratio of primary to secondary bile acids was 3.5:1. This ratio was, however, significantly higher in cholelithiasis than in the control group (5.34:1; P < 0.001); patients with carcinoma of the gall bladder had significantly higher secondary bile acids (1:1; P < 0.001). This is due to a marked increase in the secondary bile acids and indicates that raised biliary deoxycholate concentrations are present in patients with carcinoma of the gall bladder and therefore may well be a factor in carcinogenesis. PMID- 8461867 TI - Sulphated bile acid per se inhibits colonic carcinogenesis in mice. AB - Peroral sulpholithocholic acid (SLC) promoted colonic tumorigenesis in conventional rats. We then tested this compound in the mouse, a species with different bile acid metabolism from the rat. Female conventional ICR mice received 0.5 mg of N-methyl-N-nitrosourea (MNU) three times in one week intrarectally or 16 mg/kg body weight of 1,2-dimethylhydrazine (DMH) subcutaneously once a week for 10 weeks, followed by a basal diet (CE-2), or CE-2 containing SLC or lithocholic acid (LC) (both at 0.5 mmol/100 g CE-2) for 40 weeks. At autopsy, numbers of mice bearing colonic neoplasms were 4/26 (15%) in the MNU + CE-2, 4/23 (17%) in the MNU + SLC, 5/28 (18%) in the MNU + LC, 12/24 (50%) in the DMH + CE-2, 6/23 (26%) in the DMH + SLC and 11/27 (41%) in the DMH + LC group. The DMH + SLC group had less adenocarcinomas than did the DMH + CE-2 and the DMH + LC group (P < 0.05). Total faecal bile acids in the mice fed on bile salts showed threefold increases compared with those on the basal diet. Sulphates constituted an average 7% and 19% of faecal bile acids in the MNU + SLC and DMH + SLC group, respectively. These results indicated that effects of peroral SLC on colonic carcinogenesis correlated with the degree of desulphation of SLC in the intestine and sulphates per se inhibited colonic carcinogenesis. PMID- 8461868 TI - A medico-legal enquiry and its consequences: labels to remind women to have cervical smears. PMID- 8461869 TI - Mortality trends of different localizations of cancer in Spain (1951-87). PMID- 8461870 TI - Colorectal cancer and dietary calcium: a word of hope. PMID- 8461871 TI - Primary prevention: knowledge and action. PMID- 8461872 TI - Dietary non-nutritive cancer protective factors. AB - It has been widely believed that the majority of cancers in humans were caused by exposure to environmental carcinogens. The pronounced variation in incidence rates of specific cancers from one country to another was explained by a variation in the load of carcinogens to which people were exposed from the sea of carcinogens in which they lived. This native and simple point of view can no longer be upheld. It is becoming evident that this theory cannot quantitatively explain the observed occurrence of cancer. Variations in the intake of compounds with anticarcinogenic effects might just as well be made responsible for a major part of the variation in cancer incidence. A review is given of this emerging field and it is argued that the study of anticarcinogens may allow us to reach a more balanced concept of the causative network in human cancer. It should also equip us with better means for more effective cancer prevention. PMID- 8461873 TI - A technique to prepare boronated B72.3 monoclonal antibody for boron neutron capture therapy. AB - B72.3 monoclonal antibody has been successfully boronated using mercaptoundecahydro-closo-dodecaborate (boron cage compound). The reagent was incorporated by first reacting the lysine residues of the antibody with m maleimidobenzoyl succinimide ester (MBS), followed by Michael addition to the maleimido group by the mercapto boron cage compound to form a physiologically stable thioether linkage. Boron content of the antibody was determined by atomic absorption spectroscopy. For biodistribution studies, boronated antibody was radioiodinated with idogen. 125I-labeled and boronated B72.3 monoclonal antibody demonstrated clear tumor localization when administered via tail vein injections to athymic nude mice bearing LS174-T tumor xenografts. Boronated antibody was calculated to deliver 10(6) boron atoms per tumor cell. Although this falls short of the specific boron content originally proposed as necessary for boron neutron capture therapy (BNCT), recent calculations suggest that far fewer atoms of 10B per tumor cell would be necessary to effect successful BNCT when the boron is targeted to the tumor cell membrane. PMID- 8461874 TI - Correlation of lipophilicity to biodistribution of 99mTc-labelled aminothiols. AB - A series of 99mTc-DADT complexes substituted with heterocyclic amines were synthesized and tested for their ability to cross the BBB. Each 99mTc-DADT complex analysed by HPLC was found to consist of two epimers. The more lipophilic epimers were biodistributed in mice. The data demonstrated a significant brain uptake (3-12% dose/g whole brain) and a high lung accumulation (11-85% dose/g) at 2 min p.i. Between the partition coefficients of the technetium complexes, a linear correlation for lung accumulation was observed, while a parabolic curve for brain uptake was found. PMID- 8461875 TI - 99mTc-DADT complexes substituted with heterocyclic amines: effect of substitution on in vivo reactivity. AB - Alkylpiperidinyl and alkylpyrrolidinyl 99mTc-DADT complexes were synthesized and tested for their ability to cross the BBB. Each complex was a mixture of two epimers separated by HPLC. More lipophilic epimers were biologically evaluated in mice, at various time intervals. Similar biodistribution patterns were obtained for both piperidinyl and pyrrolidinyl DADT-complexes. Brain uptake or retention was influenced by the heterocyclic amine introduced into the DADT backbone. Subcellular concentration of selected 99mTc-DADT complexes was more profound in crude nuclear and post-microsomal fractions. Moreover, interaction of 99mTc 2,2,6,6,9,9-hexamethyl-4,7-diaza-4-(3-methylpyrroli dinyl)-ethyl-1,10- decanedithiol with either lipids or microsomes of whole brain was almost unaffected by time. This may suggest that a possible selective site of interaction and metabolism for DADT complexes occurs in brain. PMID- 8461876 TI - [35S]cysteamine: facile synthesis, in vivo biokinetics, and subcellular distribution. AB - Whereas chemical radioprotection against external beams of ionizing radiation is well studied in radiobiology, the aspects relating to tissue incorporated radionuclides have received little attention. The increased use of radionuclides in diagnostic and therapeutic nuclear medicine, as well as the presence of both manmade and natural radioactivity in the environment, indeed call for such investigations. Our ongoing work on a variety of radioprotectors has revealed that cysteamine (MEA), S-2-aminoethylisothio uroniumbromide hydrobromide (AET), and others (e.g. ascorbic acid), protect spermatogonial cells in mouse testis from the effects of chronic irradiation with intratesticularly localized radionuclides. In these experiments, dose modification factors ranging from 2 to 4 and 10 to 14 were obtained using spermhead survival and induction of spermhead abnormalities, respectively, as the biological end points. Similar experiments were carried out by changing the mode of administration of cysteamine to oral intubation. In these studies a dose modification factor of approximately 3 was observed in the spermhead survival assay. In an effort to understand the protection offered by MEA, the present work describes a one-pot synthesis of high specific activity [35S]cysteamine from elemental [35S]sulphur and its use in determining the biokinetics and biodistribution of MEA following intratesticular (i.t.) or oral administration in mice. PMID- 8461877 TI - Investigation of two new [99mTc]Tc-HEDP preparations that can be expected to give a better lesion-to-normal-bone uptake ratio when used as bone scanning agents. AB - Two new potential bone scanning agents have been prepared and characterized. One of the agents, Tc(Sn,pH 12)-HEDP, is prepared at pH 12 (and subsequently neutralized). The other agent, Tc(Fe)-HEDP, is prepared by reducing [99mTc]TcO4- by a mixture of Fe(II) and Sn(II). From ion exchange chromatography on Aminex A 28 it appeared that the proportion of early eluting components of the two new agents is larger than that of the usual agent, Tc(Sn,pH 7.4)-HEDP. The stabilities on storage, and in serum, of the three agents appeared to be equally good. The adsorption on tri-calciumphosphate of Tc(Fe)-HEDP and Tc(Sn,pH 7.4) HEDP was determined at several values of concentrations of Sn(II) and HEDP. Further, the influence of the pH (1-12) during reduction of [99mTc]TcO4- by Sn(II) on the adsorption of the agent on tri-calciumphosphate (at a fixed pH of 7.4) was investigated. It appeared that the adsorption of Tc(Sn,pH 12)-HEDP and Tc(Fe)-HEDP is less than that of Tc(Sn,pH 7.4)-HEDP. It is argued that this result points to a better efficiency in lesion detection of the two new agents, compared to the usual one. PMID- 8461878 TI - Synthesis, radiolabeling and tissue distribution of 11 beta-fluoroalkyl- and 11 beta-fluoroalkoxy-substituted estrogens: target tissue uptake selectivity and defluorination of a homologous series of fluorine-18-labeled estrogens. AB - We have synthesized six estrogens substituted at the 11 beta-position with a fluoroalkyl or fluoroalkoxy substituent. These compounds bind to the estrogen receptor with moderate to high affinity, with the fluoroalkyl analogs being higher affinity binders than the fluoroalkoxy ones. All of these fluorine substituted estrogens were prepared in fluorine-18-labeled form, with high radiochemical purity and at effective specific activities (15.4-50.4 TBq/mmol; 415-1362 Ci/mmol) adequate for biodistribution studies. In immature female rats, five of the six fluoroestrogens showed selective uptake by the uterus, with uterine uptake as a percent of the injected dose per gram being 4-9% at 1 h, and uterus-to-blood or uterus-to-muscle ratios being 10-40. Selective uterine uptake was eliminated by co-administration of a blocking dose of unlabeled estradiol. The only compound that did not show selective uterine uptake was 11 beta fluoropropoxyl estradiol; its rapid metabolism and its low affinity for the estrogen receptor, particularly at 25 degrees C, may account for its lack of specific uptake. The level of bone activity, an index of metabolic defluorination, shows that the defluorination rates of these six estrogens are a complex function of structure and functionality. Least prone to defluorination is 11 beta-(2-fluoroethoxy)estradiol and most prone is 11 beta-(2 fluoroethyl)estradiol. The extent of defluorination of the remaining compounds shows weak evidence for the protective effect of a heteroatom-substituted beta to the site of metabolism (the CH bonds on the fluorine-bearing carbon atom). The binding affinity, tissue distribution and metabolism of these 11 beta-fluoroalkyl and fluoroalkoxy-substituted estrogens further our understanding of the behavior of fluorine-18-labeled estrogens as potential imaging agents for estrogen receptor-positive breast cancer. PMID- 8461879 TI - Metabolism in vitro of radioiodinated N-isopropyl-p-iodoamphetamine by isolated hepatocytes. AB - An in vitro technique for the determination of radiopharmaceutical metabolism has been developed using isolated hepatocytes. Radioiodinated N-isopropyl-p iodoamphetamine (IMP; iofetamine, USP) was employed a model tracer in these studies because its labeled metabolites are well-characterized. Hepatocytes isolated from the rat and human produced labeled metabolites in vitro for up to 4 h in a manner similar to that reported for humans in vivo. Identical metabolites were generated by all cell types investigated, but the rate of metabolism differed (rat >> human; female > male; fresh > frozen). The utility of this methodology for the preclinical evaluation of potential radiopharmaceuticals is described. PMID- 8461880 TI - Compartmental analysis of the pharmacokinetics of radioiodinated monoclonal antibody B72.3 in colon cancer patients. AB - Sixteen patients with colorectal cancer were administered 37-74 MBq (1 mg) of radioiodinated B72.3 monoclonal antibody. Pharmacokinetic analysis was carried out on plasma and urine samples. Elimination from the plasma was biexponential with a mean T1/2 alpha of 3.7 h and T1/2 beta of 62.4 h. The plasma clearance was fit to a two-compartmental model. This was combined with a previously reported model for radioiodine to construct a composite model. There was a good correlation (r = 0.952) between the model-predicted and observed excretion of radioiodine suggesting that the composite model is compatible with the pharmacokinetics of the radiolabelled antibody. PMID- 8461881 TI - The stability in liver homogenates of indium-111 and yttrium-90 attached to antibody via two popular chelators. AB - To investigate the influence of chelator on the stability in liver homogenates of 111In and 90Y-labeled antibodies, the C110 antibody was conjugated with the cyclic anhydride of DTPA (cDTPA) and with isocyanatobenzyl-DTPA (SCN-Bz-DTPA) and labeled with both radionuclides. After incubation in fresh liver homogenates at 37 degrees C for 1-2 days, the soluble fraction was analyzed by filtration, HPLC and TLC to determine the nature and extent of transchelation of the label and catabolism of the antibody. The loss of activity from antibody, as shown by passage through a low molecular weight (10 kDa cut-off) filter, was 3-5 times more pronounced for 90Y (51 and 68% at 1 and 2 days) than 111In (11 and 29%, respectively). No significant difference was observed between chelators. Furthermore, analysis of these low molecular weight species showed that even at 1 day, 90Y in contrast to 111In was present as one or more weak complexes and therefore no longer chelated to either DTPA or Bz-DTPA. Little evidence was observed for instability in liver of the thiourea bond whereby SCN-Bz-DTPA is attached to the antibody. By contrast the identification of 111In-DTPA in the homogenates demonstrates the instability of the amide bond generated by cDTPA conjugation. In conclusion, as expected, 90Y was shown to form less stable chelates than 111In, however, in this investigation the greater denticity of Bz DTPA over DTPA did not improve stability with either radiolabel. PMID- 8461882 TI - An improved synthesis of [125I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma. AB - To improve the radiolabeling yield and the specific activity of [125I]N-(2 diethylaminoethyl)-4-iodobenzamide (DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [125I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [125I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung, was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma. PMID- 8461883 TI - Synthesis and biodistribution of 18F-labeled fleroxacin. AB - [18F]Fleroxacin (6,8-difluoro-1,4-dihydro-1-(2-[18F]fluoroethyl)-4- oxo-7-(4 methyl-1-piperazinyl)-3-quinolinecarboxylic acid) was synthesized from its methylsulfonyl ester precursor. 6,7,8-Trifluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester (Ro 19-7423) was alkylated with 2-bromoethanol to produce 6,7,8 trifluoro-1,4-dihydro-1-(2-hydroxyethyl)-4-oxo-3-quinolinecarboxyl ic acid ethyl ester in 76% yield which was then condensed with 1-methyl-piperazine to produce 6,8-difluoro-1,4-dihydro-1-(2-hydroxyethyl)-7-(4-methyl-1-piperazinyl)4- oxo-3- quinolinecarboxylic acid ethyl ester in 67% yield. This product was reacted with methanesulfonyl chloride to produce the mesylate precursor of fleroxacin in 66% yield. Nucleophilic substitution of the mesylate with 18F- in the presence of Kryptofix 2.2.2 followed by basic hydrolysis produced [18F]fleroxacin with a radiochemical yield of 5-8% [EOS] within 90 min. The pattern of biodistribution of [18F]fleroxacin was similar to the 14C-labeled drug. PMID- 8461884 TI - Clearance and distribution parameters of 99mTc-EHIDA, -DTPA and -MAG-3 by dynamic liver/kidney scintigraphy. AB - The radiopharmaceuticals (RF) EHIDA, DTPA and MAG-3 (labeled by 99mTc), commonly used in dynamic liver/kidney scintigraphy, are distributed in intravascular (i.v.) and extravascular (e.v.) spaces, as they are simultaneously cleared from the blood passing through their target organ (liver/kidney). The drop in concentration of these RF in blood is therefore determined by distribution as well as by clearance up to the time of equilibrium. From that time only the rate of decrease of RF in blood expresses the "true" (liver/kidney) clearance and this clearance parameter is a clinically reliable index of the function of the target organ. (A) The method of analysis of the clearance curve obtained from the heart region has been reported; the method is based on a physiological approach with respect to the distribution processes of the RF in the organism. Apart from the main important parameter, T (clear) (half-time of the "pure" clearance of the resp. RF from its distribution space), two further parameters are obtained: T (distr.) (half-time of the e.v. distribution of the RF) and END (distr.) (end of this distribution). (B) The results of 218 patients examined using 99mTc-EHIDA, 192 using DTPA and 65 using MAG-3 have been statistically processed. The mutual correlation of all parameters [T (distr.), END (distr.), T (clear)] within each group of patients as well as the differences of corresponding parameters between the groups of patients are studied. The main purpose of the work was to obtain the reliable clearance parameters of the RF with extravascular distribution for routine clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461885 TI - L-[2-18F]fluorophenylalanine and L-[U-14C]phenylalanine: a comparative study of their transport to rat brain. AB - The transport rates of L-[2-18F]fluorophenylalanine ([18F]Phe) and L-[U 14C]phenylalanine ([14C]Phe) across the blood-brain barrier were compared in saline, large neutral amino acids (NAA) and large basic amino acids (BAA) loaded rats. The fraction of transported tracer (FTT) was expressed as the ratio of brain radioactivity to integrated plasma radioactivity at 5 min after injection of the tracers. Cerebral FTTs of [18F]Phe and [14C]Phe in the control group were 0.042 and 0.045, respectively, and decreased to 0.016 and 0.019 in the NAA loaded group. The ratios of FTT of [18F]Phe and that of [14C]Phe were approx. 0.90, and did not differ among the three groups. These results indicate that the transport of [18F]Phe from the blood to the brain can be considered to be mediated by the NAA transport system and that its transport rate is almost the same as that of [14C]Phe. PMID- 8461886 TI - DNA fingerprinting of Trypanosoma vivax isolates rapidly identifies intraspecific relationships. AB - Using the polymerase chain reaction and arbitrarily selected oligonucleotide primers of 10 or 11 bases, we have amplified DNA sequences from Trypanosoma vivax parasites isolated from South America and Africa. On the basis of polymorphisms in the DNA fingerprints generated by three of the primers, the parasites could be separated into two major groups, one comprising T. vivax isolates from Kenya and the second including all the other T. vivax parasites (from Colombia, The Gambia, Nigeria and Uganda). One of these three primers (ILo 525) also gave isolate specific DNA fingerprints for the parasites tested, which will allow the use of this technique both in the species identification and discrimination of T. vivax parasites. PMID- 8461887 TI - Effect of low temperature on the in vitro growth of Plasmodium falciparum. AB - The effect of low incubation temperature on synchronized cultures of Plasmodium falciparum was studied. Young trophozoites that were maintained at 28 degrees C matured slowly and invaded poorly. Growth seemed to arrest when parasites reached a maturation equivalent to 30 h, although they reestablished their growth normally when returned to 37 degrees C. On the other hand, 36-h synchronized parasites that were transferred to 28 degrees C completed their cell cycle with a 12-16 h delay, but without changes in the parasite as seen by light microscopy and without a diminution in the efficiency of the invasion or in the incorporation of 35S-methionine. These results might be useful for obtaining parasites at defined stages of development at the desired time. PMID- 8461888 TI - An improved medium for Plasmodium chabaudi in vitro erythrocyte invasion assays. AB - RPMI-1640 is routinely used as the basal medium for the in vitro maintenance of malaria parasites. In this study we tested several commercially available nutritional media in a Plasmodium chabaudi chabaudi erythrocyte invasion assay and showed that three media, BME Basal Medium--modified, Dulbecco's Modified Eagle Medium, and William's Medium E, improved the level of merozoite invasion when compared with RPMI-1640. These media improve the rate of maturation of newly invaded rings to young trophozoites. Radioisotope incorporation by trophozoites maintained in these three media was also improved when compared to trophozoites maintained in RPMI-1640. BME Basal Medium--modified, or a combination of three parts BME Basal Medium--modified with one part William's Medium E, supported higher levels of erythrocyte invasion by merozoites. We suggest that either of these media replace the currently used RPMI-1640 for in vitro studies on P. c. chabaudi. PMID- 8461889 TI - Ultrastructural and cytochemical identification of peroxisomes in the ciliate Ichthyophthirius multifiliis. AB - The peroxisomes of the parasitic ciliate Ichthyophthirius multifiliis were studied, using ultrastructural and cytochemical techniques. In this ciliate most peroxisomes possess a circular or oval section less than 0.6 micron in diameter. However, some dumbbell-shaped and elongated peroxisomes could also be observed. These organelles were frequently associated with the mitochondria and were more abundant in the cell cortex than in the center of the ciliate. Small vesicles and dense nucleoids were usually present in the ultrathin sections of these peroxisomes. Peroxisomal vesicles and tubular structures were selectively impregnated with osmium tetroxide. Catalase was detected by cytochemical techniques in I. multifiliis peroxisomes. PMID- 8461890 TI - Reclinomonas americana N. G., N. Sp., a new freshwater heterotrophic flagellate. AB - A new heterotrophic flagellate has been discovered from sites in Maryland, Michigan and Wyoming. The flagellate resides within a lorica constructed of a meshwork of intertwined fibrils with the outer surface invested with nail-shaped spines. The organism "reclines" within the lorica with its ventral aspect directed upward, and has two heterodynamic flagella, neither of which bears mastigonemes. One flagellum is directed upward and the other is arched over the ventral aspect of the body. Ingestion of bacteria takes place at the left posterior half of the cell. The organism is anchored to the lorica on the right posterior side by a series of regularly spaced cytoplasmic bridges and at the left anterior of the cell by a cytoplasmic appendage similar to the "languette cytoplasmique" found in some bicosoecids. The right side of the cell is raised into a flattened lip with the outer margin reinforced by a ribbon of microtubules. The new flagellate has mitochondria with tubular cristae and lacks a Golgi. A new genus is created to accommodate both the new flagellate described herein and Histiona campanula Penard. A new family is proposed to include the new genus and Histiona. PMID- 8461891 TI - A group I intron in the SSUrDNA of some Naegleria spp. demonstrated by polymerase chain reaction amplification. AB - The small subunit ribosomal DNA (SSUrDNA) of all described Naegleria spp. was amplified by polymerase chain reaction with universal primers. In all strains of N. andersoni andersoni, N. andersoni jamiesoni, N. australiensis italica and two related strains, and one out of four clusters of N. gruberi, a band of approximately 3.3 kb was obtained. All other strains displayed a band with the expected DNA length of 2.0 kb. This means the former have a 1.3 kb intron in the SSUrDNA. Restriction analysis demonstrated that the intron is between two conserved Pst I sites at the 5' end of the SSUrDNA. It also suggested the introns might not be identical in each species or subspecies. The Pst I fragment of SSUrDNA containing the 1.3 kb insert in N. andersoni andersoni was cloned and sequenced. The 1,296-nucleotide insert is situated in helix 19 of the SSUrDNA, which is an area of conserved primary and secondary structure. Sequence and secondary structure analyses of the insert revealed it it is a group I intron. This group I intron is very large and contains an open reading frame that could serve to encode a polypeptide of 139 amino acids in size. PMID- 8461892 TI - The challenge of Pneumocystis carinii culture. AB - Published and unpublished data on the cultivation of P. carinii were reviewed by a panel of investigators convened by the National Institutes of Health. Although several cell culture systems allow propagation of P. carinii for a limited time with modest rates of replication, these have not proved adequate for isolation of P. carinii in sufficient quantity to explore important basic biological investigation. Attempts at cell-free culture have yielded only transient proliferation. Because much of the unsuccessful work on cultivation of the organism has been unpublished, the panel agreed that these data may be useful to other investigators in designing experimental strategies for cultivation. Therefore, the purpose of this report is to make available this information to researchers, lest others unknowingly repeat unsuccessful methods. It is hoped that by documenting the history and the complexities of Pneumocystis culture, renewed interest and efforts will be directed toward this fundamental scientific challenge. PMID- 8461893 TI - Leishmania differentiation in natural and unnatural sand fly hosts. AB - Leishmania differentiation in the gut of phlebotomine sand flies was evaluated based on five light and electron microscopic studies of natural (Leishmania panamensis/Lutzomyia gomezi, Leishmania chagasi/Lutzomyia longipalpis) and unnatural (Leishmania mexicana/Lutzomyia abonnenci, Leishmania panamensis/Phlebotomus papatasi, Leishmania major/Lutzomyia longipalpis) life cycles. In the bloodmeal, transformation of amastigotes into stumpy promastigotes occurred before or during division. Further division in pairs or rosettes resulted in the development of spatulate and/or elongate nectomonad (free swimming) promastigotes. Elongate, short, and metacyclic nectomonad promastigotes, and nectomonad paramastigotes were present in the midgut lumen. Dividing short promastigotes predominated in the cardia, and appeared to generate metacyclic forms which were observed in three life cycles. Haptomonad (attached) forms of Leishmania panamensis in the hindgut were primarily spatulate promastigotes (natural host) or pear-shaped promastigotes (unnatural host); paramastigotes and dividing forms were rare. At the stomodeal valve, short haptomonad promastigotes predominated in unnatural hosts, while both short and pear-shaped haptomonads were abundant, along with paramastigotes in natural hosts. Haptomonad paramastigotes and pear-shaped promastigotes colonized the esophagus, while paramastigotes predominated in the pharynx. Metacyclics were free-swimming in the lumen of the foregut. PMID- 8461894 TI - Developmentally-regulated virulence factors of Trypanosoma cruzi and their relationship to evasion of host defences. AB - Developmental preadaptation of virulent stages of Trypanosoma cruzi correlates with their ability to survive and establish infection in mammalian hosts. Infective trypomastigote stages must first preadapt to survival in the extracellular milieu and then to the rigors of establishing an intracellular infection. Selected phenotypic variations in evading host defences have been correlated with expression of stage-specific proteins or functions. Resistance of trypomastigotes to complement-mediated killing correlates with the presence of a stage-specific molecule that exhibits an analogous function to mammalian decay accelerating factor, and with the presence of a neuraminidase/trans-sialidase that transfers sialic acid moieties to the parasite surface, thereby enabling it to avoid complement activation. Trypomastigotes enter cells by a mechanism that involves sorting of cell surface receptors and avoids eliciting a respiratory burst. Once within a membrane-bound vacuole, which undergoes acidification, the neuraminidase/trans-sialidase and an acid-active, transmembrane pore-forming protein are released by the parasite and are capable of acting together to accelerate rupture of the vacuolar membrane and the parasite's escape into the cytoplasm of the host cell. Escape from the parasitophorous vacuole allows virulent stages of T. cruzi to avoid compartmental, non-oxidative killing mechanisms such as degradation by lysosomal hydrolases. PMID- 8461896 TI - Absence of transitory [Ca2+]i flux during early in vitro metacyclogenesis of Trypanosoma cruzi. AB - The phorbol ester TPA (phorbol 12-myristate 13-acetate) substitutes for CO2 as an agonist for transforming Trypanosoma cruzi epimastigotes to the metacyclic trypomastigote stage in a starvation medium consisting of phosphate buffered saline + 10 mM proline, 10 mM sodium acetate and 0.035% NaHCO3. Since TPA is thought to stimulate protein kinase C by mimicking the activity of the secondary messenger diacylglycerol, the above result suggested that T. cruzi metacyclogenesis could be activated by a Ca(2+)-dependent protein kinase C signal induction pathway. Accordingly, cytosolic calcium flux ([Ca2+]i) in epimastigotes, activated with 5% CO2 or TPA (10(-7) M), was measured with the Ca2+ molecular probe, fluo-3AM. In addition, [Ca2+]i was measured in cells incubated with putative metacyclogenic agonists (e.g. proline, glutamate, bioamines, ionophores and catecholamines). None of the compounds studies, except for EGTA, affected cytosolic Ca2+ levels. Control assays with 11 microM thapsigargin, which mobilizes noncytoplasmic Ca2+ stores by inhibiting endoplasmic reticulum Ca(2+)-ATPase, validated our fluorometric assay procedure. Although thapsigargin significantly increases cytoplasmic Ca2+ fluorescence, it has no effect on transformation. The protein kinase C inhibitors staurosporine, H 7 and HA 1004 were tested for their effect on T. cruzi metacyclogenesis. Low concentrations of staurosporine and HA 1004 significantly elevated Peru strain transformation while H-7 had no effect on Peru strain metacyclogenesis. Inhibitor H-7 did significantly depress CL transformation. The results indicate that induction of T. cruzi metacyclic trypomastigote formation by CO2 and TPA is not accompanied by changes in cytosolic Ca2+ and do not provide supporting evidence for participation of a protein kinase C-mediated phosphoinositide cascade in metacyclogenesis. PMID- 8461895 TI - Developmental life cycle of Leishmania--cultivation and characterization of cultured extracellular amastigotes. AB - The biochemistry and immunology of Leishmania promastigotes has been extensively studied; this is due primarily to the facility with which this stage, in contrast to the amastigotes stage, can be maintained in axenic culture. Several attempts to axenically culture lines of Leishmania amastigotes have been reported in the literature. This paper summarizes methods of adaptation (low pH, elevated temperature and culture medium) and characterization of several axenic lines of Leishmania amastigotes. Based on morphological, biological, immunological and biochemical evidence, these organisms appear to resemble amastigotes from infected macrophages or tissue. The axenically cultured amastigotes appear to be distinct from shocked (heat, serum deprivation, stressed) Leishmania promastigotes in the plethora of proteins synthesized, growth (multiplication) in culture, and developmental regulation observed. These data suggest that Leishmania organisms have a significant developmental response to certain signals (pH, temperature) mimicking their in vivo macrophage milieu. The response to other environmental parameters characteristic of the host-macrophage remain to be determined. These axenically cultured amastigotes should be of interest for further immunological, biochemical and developmental investigations of the disease-maintaining stage of this parasite. PMID- 8461897 TI - Introduction of loop sutures in microsurgical telescoping anastomosis. AB - We have designed a loop suture technique for use in microsurgical telescoping (sleeve) anastomosis to prevent problems from the free floating inserted vessel stump. The patency rate of rat femoral arteries repaired with this technique was 95% and that of interpositional vein grafts, in which both the proximal and distal anastomoses were completed with the same sleeve technique, was 81.0%. PMID- 8461898 TI - Healing of microvenous PTFE prostheses implanted into the rat femoral vein. AB - 44 PTFE prostheses (Gore-Tex; ID 1 mm) were implanted into rats' femoral veins by means of the sleeve anastomotic technique and were evaluated at regular intervals from 1 h up till 24 weeks after implantation by means of light and electron microscopy to study in detail their healing process. All prostheses, except one at 1 week and one at 24 weeks after implantation, were patent at the time of removal. Upon implantation, the luminal surface of the prostheses became covered with a thin clot layer. From 1 week onwards, endothelial cells originating from the anastomotic sides grew in across the anastomoses. In addition, small capillary-like orifices were present at the anastomotic sites, from which endothelial cells also seemed to originate. At 2 weeks, in several areas in the mid-region of the prostheses, the fronts of regenerating endothelial cells had reached each other, and about 80% of the luminal surface was covered by endothelium and at 3 weeks, the prostheses were completely covered by an endothelial layer. These results demonstrate that PTFE microvenous prostheses heal exclusively by means of rapid ingrowth of endothelial cells originating from both sides at the anastomoses. PMID- 8461899 TI - Non-radioactive coloured microsphere measurement of regional tissue blood flow for axial pattern flaps in rabbits. AB - We administered non-radioactive coloured microspheres (NRACM) to measure the regional tissue blood flow (RTBF) of eight axial pattern flaps and four kidneys in four rabbits using four repeated injections into each animal. As a control, we used radioactive microspheres (RAM) for six kidneys in three rabbits. There were no significant differences for RTBF values between NRACM and RAM, between the numbers of microspheres used (2 x 10(6) and 4 x 10(6)), or between the number of injections. These results showed that NRACM is a useful and safe laboratory method. PMID- 8461900 TI - A comparison of newborn versus old skin fibroblasts, their potential for tissue repair. AB - An assessment was made of the ability of human skin fibroblasts from newborn and old subjects to produce intracellular urokinase inhibitor and urokinase plasminogen activator when exposed to phorbol myristate acetate. Urokinase inhibitor produced by human skin fibroblasts may be essential for cell growth regulation. The expression of urokinase inhibitor and/or urokinase-plasminogen activator may possibly be age-related. The principal observation that newborn skin fibroblasts show a low level and poorly sustained production of intracellular inhibitors of urokinase could help to explain the flexibility of the wound healing process in the foetus. PMID- 8461901 TI - Role and innocuity of Tisseel, a tissue glue, in the grafting process and in vivo evolution of human cultured epidermis. AB - Cultured epidermal sheets are currently used for burn wound treatment but reported results on graft take are variable. This study was designed to evaluate the role and influence of Tisseel, a fibrin glue, in the take of cultured human epidermal sheets in an athymic mouse model. On days 4, 10 and 21 post-grafting, histology, electron microscopy and immunofluorescence staining confirmed the presence of a human epithelium and the development of a basement membrane. Tisseel was detectable on day 4 only, but overall treated and untreated grafts were similar. The use of Tisseel enhanced the mechanical stability of these fragile grafts, increased the percentage of graft take, and its innocuity on the in vivo evolution of cultured epidermal sheets was demonstrated. For these reasons, we think that Tisseel may be advantageous in a clinical setting. PMID- 8461902 TI - Epiphora in facial paralysis. 1950-1. PMID- 8461903 TI - Epiphora in facial paralysis. AB - Current management concepts of epiphora in established facial palsy are reviewed and compared with those advocated by McLaughlin and criticized by Stallard in 1949. PMID- 8461904 TI - The supramalleolar flap based on septocutaneous perforators from the peroneal vessels for intraoral soft tissue replacement. AB - In cadavers the septocutaneous perforating vessels branching off the distal segment of the peroneal artery were studied. An area of skin approximately 7 x 12 cm above the ankle was noted to be perfused by these and intraoral defects in 8 patients have been repaired using the supramalleolar flap as a variation of the peroneal flap developed by Yoshimura. Owing to its thinness and the long and wide vascular pedicle, the flap is particularly suitable for reconstructing mobile parts of the oral cavity, and in selected cases may be considered as an alternative to a radial flap. PMID- 8461905 TI - Perineural infiltration in basal cell carcinomas. AB - 4376 basal and squamous cell carcinomas were dealt with over a period of 100 months. 76.6% of these were basal cell carcinomas. Perineural spread was noted in 0.178% of basal cell lesions and in all examples was found in recurrent tumours, which were predominantly in the preauricular and malar areas in this series. PMID- 8461906 TI - Non-medical implications of malignant melanoma. AB - Insurance and mortgage companies continue to regard melanoma in a rigid and perhaps flawed way, with detrimental effect to patients' financial standing. We questioned 100 consecutive patients coming to our clinic between the ages of 20 and 50, and asked if they had had problems obtaining life insurance, mortgages etc, since they were diagnosed. A substantial proportion of patients in the younger age groups had problems with mortgage and insurance applications. PMID- 8461907 TI - Anatomical investigations of the cutaneous branches of the circumflex scapular artery and their communications. AB - The vascular anatomy of the cutaneous branches of the circumflex scapular artery and their communications with perforators supplying adjacent territories are described, based on dissections of 20 scapular regions. The cutaneous branches of the circumflex scapular artery are distributed in three areas by the ascending, horizontal and descending branches. The existence of the ascending branch was constant, confirming the reliability of the ascending scapular flap. PMID- 8461908 TI - T flap hypospadias repair in circumcised patients. AB - Single stage repair of distal penile hypospadias with chordee in circumcised patients is described. A ventral 'T' flap is used, the horizontal part of the T flap forming the complete circumference of the new urethra and lying in the defect created due to chordee release. The vertical part of the T flap, in conjunction with the grooved glans, forms the neourethra like the flip flap procedure. Of 22 patients repaired in this way, 2 (9.0%) developed fistula and one (4.5%) had meatal stenosis, thus in 86.5% successful repair was achieved. PMID- 8461909 TI - Use of the inferiorly based rectus abdominis flap for inguinal and perineal coverage--low venous pressure zone concept. AB - The authors report 8 cases of coverage of the inguinal and perineal areas with the inferiorly based rectus abdominis myocutaneous flap. This flap seems to be the technique of choice for coverage of such defects. The design of the flap can be explained by the low venous pressure zone concept. PMID- 8461910 TI - A simple device for nasal tube fixation in facial burns patients. AB - In acute facial burns, it is sometimes necessary to insert tubes down one or both nostrils. We describe a simple secure method of fixation. PMID- 8461911 TI - Thromboembolic prophylaxis in plastic surgery. PMID- 8461912 TI - Angelman syndrome. PMID- 8461913 TI - Necrotising fasciitis in the head and neck region. PMID- 8461914 TI - Extravasation injuries. AB - The leakage of cytotoxic drugs, intravenous nutrition, solutions of calcium, potassium, bicarbonate and even 10% dextrose outside the vein into which they are delivered is known not only to cause skin necrosis but also to precipitate significant scarring around tendons, nerves and joints. In this review of 96 patients with extravasation injuries seen between 1987 and 1992 at St Thomas' Hospital, Mount Vernon Hospital and The Hospital for Sick Children, Great Ormond Street, several patients required extensive reconstruction and in some, despite this, extravasation injury has rendered a limb virtually useless. Two techniques, liposuction and saline flushout, are described to remove extravasated material while conserving the overlying skin. Analysis of flushout material confirmed that the extravasated material was actually being removed. Forty four of the study group in whom noxious materials were known to have extravasated underwent such early treatment. The results in this group were quite striking--the majority (86%) healed without any soft tissue loss at all. The early referral and treatment of extravasation injuries is, therefore, recommended. PMID- 8461915 TI - A new design of the cross-finger flap: the C-ring flap. AB - A new cross-finger flap, the C-ring flap, is described for repair of degloved amputation stumps and dorsal and volar defects of the fingers. The C-ring flap is an axial pattern cross-finger flap based on one digital vascular bundle either distally or proximally. We used this flap in 12 cases with different types of finger defects. The results were satisfactory. We conclude that the C-ring cross finger flap had distinct advantages over standard cross-finger flaps. These advantages are discussed. PMID- 8461916 TI - Insulin-like growth factor-1 and biochemical markers of osteoarthritis. PMID- 8461917 TI - Central nervous system involvement in systemic lupus erythematosus. Are we any further forward? PMID- 8461918 TI - The Roche Rheumatology Prize Lecture. Complement deficiency and disease. PMID- 8461919 TI - Insulin-like growth factor-1: a prognostic factor of knee osteoarthritis. AB - During a population survey in 1975-1978 persons with radiological osteoarthritis (ROA) of the knee were identified. After 12 years a follow-up study was conducted to study the effect of circulating insulin-like growth factor-1 (IGF-1) on cartilage loss, osteophyte growth and overall progression in 141 persons with confirmed ROA of the knee. The outcome measures were scored by comparing the radiographs taken at baseline and at follow-up. Insulin-like growth factor-1 was measured by radioimmunoassay in serum taken at follow-up and in 79% of the baseline sera. After adjusting for age, gender and body mass index at baseline, IGF-1 concentration at follow-up was related to osteophyte growth and overall progression. The adjusted odds ratio of the highest vs the lowest tertile was 2.96 (95% CI: 1.15-7.60) for osteophyte growth and 2.58 (1.01-6.60) for overall progression. No clear relationship was found with cartilage loss. These results were confirmed when baseline IGF-1 was studied. We conclude that the circulating IGF-1 concentration has an effect on the course of knee OA by influencing osteophyte formation but a preventive effect on cartilage loss could not be shown. PMID- 8461920 TI - Osteoarthritic human cartilage is more sensitive to transforming growth factor beta than is normal cartilage. AB - Osteoarthritis is a degenerative joint disease, characterized by the destruction of the articular cartilage. One of the first changes in the osteoarthritic articular cartilage is a reduction in proteoglycan content. In this study we demonstrate that transforming growth factor beta (TGF beta), a multi-functional growth factor, stimulates the proteoglycan synthesis of explants from human articular knee cartilage dose-dependently in vitro. Osteoarthritic cartilage proved to be much more sensitive to stimulation by TGF beta than normal healthy cartilage. This may indicate that TGF beta plays an important role in the repair of osteoarthritic cartilage. PMID- 8461921 TI - Anti-P antibodies are associated with psychiatric and focal cerebral disorders in patients with systemic lupus erythematosus. AB - In a cross-sectional study, 62 patients with systemic lupus erythematosus were assessed using standardized psychiatric and psychological methods; systemic disease activity was scored using the British Isles Lupus Assessment Group and the Lupus Activity Criteria Count indices. IgG and IgM anti-P antibodies were measured by ELISA using a synthetic 22 amino acid peptide as the relevant antigen. IgG and IgM anti-P antibodies were significantly associated with neuropsychiatric disorders (psychiatric and neurological) but failed to distinguish patients with psychiatric disorders from those with neurological disorders. These antibodies were not associated with cognitive impairment or systemic disease activity. PMID- 8461922 TI - Cognitive impairment and autoantibodies in systemic lupus erythematosus. AB - Nervous system involvement in systemic lupus erythematosus (SLE) includes a wide array of manifestations some of which have been associated with specific autoantibodies. These include reactivity to surface neuronal and lymphocyte antigens, ribosomal P and cardiolipin. The aim of the present study was to examine the association between cognitive abnormalities and these autoantibodies in an unselected female population of SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared to 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Circulating antineuronal antibodies were measured by indirect immunofluorescence using human neuroblastoma cell lines IMR-6 and SK-N-SH. Lymphocytotoxic antibodies were measured by microcytotoxicity. Antibodies to ribosomal P and cardiolipin were measured by ELISA. Antineuronal antibodies were detected in 34%, lymphocytotoxic antibodies in 47%, anti-P antibodies in 17% and anticardiolipin antibodies in 24% of patients. In the cognitively impaired and unimpaired SLE patients there was no significant difference in the prevalence of antineuronal antibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%), anti-P antibodies (20 vs 17%) or anticardiolipin antibodies (7 vs 29%). The titre and isotype of autoantibodies were also similar in both groups. These results suggest that autoantibodies which have previously been associated with nervous system manifestations of SLE are not likely to be directly involved in the pathogenesis of cognitive dysfunction. PMID- 8461923 TI - Patients with anticentromere antibodies, clinical features, diagnoses and evolution. AB - The sera of 1373 patients derived from a random population of 2627 individuals examined in a rheumatology outpatient clinic were found to be positive for antinuclear antibodies (ANA). Forty-seven of 1373 ANA positive patients (3.42%) presented a pattern of anticentromere antibodies (ACA), and of these 41 were followed-up. The predominant clinical features among ACA positive patients were Raynaud's phenomenon, arthralgias, scleroderma affecting the hands, feet, face and forearms, telangiectases and pulmonary involvement. There were 26 patients (64%) with limited cutaneous systemic sclerosis (lSSc), seven with primary Sjogren's syndrome (Ss) (17%), five with idiopathic Raynaud's phenomenon (IRPh) (12%) and three (7%) with other diseases. The lSSc subset was characterized by a significantly younger age for disease onset than for the IRPh patients. The Raynaud's phenomenon of lSSc patients lasted for many years before the onset of scleroderma, while their pulmonary involvement was mild and subclinical. The Ss patients with ACA were characterized by a lower incidence of parotid gland enlargement and anti-La (SSB) antibodies than described in the literature. Finally, the presence of ACA correlates with the clinical criteria proposed for the diagnosis of lSSc. PMID- 8461924 TI - Physiological variations in the urinary excretion of pyridinium crosslinks of collagen. AB - To further validate measurements of the pyridinium crosslinks of collagen as indices primarily of bone resorption in arthritis and other diseases, the effects of day-to-day and nyctohemeral parallel variations, and of renal impairment have been studied. Day-to-day variations measured over 3 weeks were between 16 and 24% for a group of post-menopausal women. Nyctohemeral variations in crosslink excretion of 10-15% were recorded. Although crosslink excretion relative to creatinine was generally higher in the morning than in the evening, no consistent pattern was observed between healthy male and female volunteers and a group of patients with OA or RA. For patients with impaired renal function, with or without arthritis, there was no correlation between crosslink excretion and either creatinine clearance rates or urinary N-acetyl glucosaminidase activity. These results suggested that there was no direct relationship between renal function, at the glomerular or tubular level, and crosslink excretion. PMID- 8461925 TI - Pelvic insufficiency fractures in rheumatoid arthritis. AB - The occurrence of pelvic insufficiency fractures in patients with rheumatoid arthritis has not previously been well emphasized. These fractures are difficult to detect clinically and appropriate radiological investigation is necessary for diagnosis. We describe five patients with a spectrum of radiological features and discuss the approach to diagnosis and treatment of these lesions. PMID- 8461926 TI - A complicated case of systemic lupus erythematosus. PMID- 8461927 TI - Autoantibodies in central nervous system lupus. AB - Central nervous system (CNS) involvement in patients with lupus remains both a diagnostic and a therapeutic challenge. The role of autoantibodies in the pathogenesis of CNS lupus and/or as markers for disease activity is reviewed. Doubt is cast on the value of measuring anti-neuronal antibodies. Those antibodies binding ribosomal-P protein antigens or certain phospholipids appear to have greater utility, although even in these cases there is no uniform agreement as to their precise role in CNS disease induction, or how well antibody levels reflect disease activity. PMID- 8461928 TI - Antibodies to type II collagen in early rheumatoid arthritis. AB - Antibodies to native and denatured type II collagen were investigated in a group of 79 patients with rheumatoid arthritis (RA) of disease duration less than 12 months (median 8 months; range 3-12 months). Using a solid-phase ELISA to measure these antibodies, the incidence of patients with levels above the upper limit of normal (mean of normal plus 3 SD) was low as compared to previous findings in patients with established disease. The majority of positive sera contained small amounts of IgM antibodies to denatured type II collagen whilst a few had IgG antibodies to native and denatured type II collagen. These findings suggest that the production of high levels of serum anti-type II collagen antibodies in patients with RA is a secondary phenomenon, which may exacerbate the disease rather than be a primary cause of disease. PMID- 8461929 TI - Familial scleroderma: HLA antigens and autoantibodies. AB - We report clinical and serological findings as well as the results of extended (HLA-A, B, C, DR and complotype) haplotype determinations of a family with two cases of systemic scleroderma and one case of primary biliary cirrhosis and incomplete CREST syndrome in a sibship of eight. In addition, one of these eight siblings has showed immunological findings of autoimmune disease for years but has not developed clinical symptoms. This family was studied by Soppi et al. in 1982; one member of the family has since then developed primary biliary cirrhosis and incomplete CREST type scleroderma. All family members with scleroderma or related disease as well as their sister with immunological abnormalities share the A2; B8; DR3 haplotype. Also some members of the family share the same haplotype but have remained healthy. This haplotype seems to be a predisposing factor but additional genetic or environmental factors are probably necessary for expression of autoimmune disease. PMID- 8461930 TI - Vertebral osteomyelitis due to Staphylococcus epidermidis. AB - Vertebral osteomyelitis due to Staphylococcus epidermidis is extremely rare and usually occurs in the context of immunosuppression in association with an adequate portal of entry for infection. This paper reports a case of vertebral osteomyelitis due to S. epidermidis in a man with no evidence of immunosuppression or obvious portal of entry. The patient presented with severe back pain but there were no clinical signs of infection. Radiographs and computerized tomographs showed destruction of thoracic vertebral bodies and an adjacent soft tissue mass. S. epidermidis was grown from multiple blood cultures. All isolates had identical antibiograms and biochemical profiles. There was evidence of healing of the vertebral bodies and resolution of the soft tissue mass after appropriate antistaphylococcal treatment. PMID- 8461931 TI - Group G streptococcal osteomyelitis of the spine. AB - Two elderly men, one with definite and one with probable malignancy, presented with severe back pain. Both had osteomyelitis of the lumbar spine due to Group G streptococci which responded to chemotherapy. PMID- 8461932 TI - Q-fever polyarthritis. PMID- 8461933 TI - Differential therapeutic response in AIDS-associated polyarthritis. PMID- 8461934 TI - HLA-DR antigens in rheumatic fever and rheumatic heart disease patients. PMID- 8461935 TI - Mixed connective tissue disease--a farewell? PMID- 8461936 TI - UCTD or U1 RNP-associated connective tissue syndrome. PMID- 8461937 TI - Cytokine inter-relationships and their association with disease activity in arthritis. PMID- 8461938 TI - Sensorineural hearing loss in juvenile chronic arthritis. PMID- 8461939 TI - Pseudogout mimicking meningitis. PMID- 8461941 TI - The use of monoclonal antibodies for the diagnosis and therapy of bladder cancer. PMID- 8461940 TI - Cyclosporin A in the treatment of relapsing polychondritis with severe recurrent eye involvement. PMID- 8461942 TI - Validation of a non-invasive radioisotope method of imaging ureteric urine transport. AB - Measurement of ureteric function has hitherto involved the use of invasive techniques. A non-invasive, radioisotope method of imaging and displaying individual ureteric boluses has been described, a refinement of which is used in this department. Each "spindle" displayed using this technique theoretically represents an individual ureteric bolus of urine, but the technique has never been validated in the normal ureter in either the experimental model or man. A porcine model was set up to allow simultaneous measurement of ureteric bolus transmission using the radioisotope (compressed image) method and by the accepted techniques of electromyography (EMG) and urine drop counting. The timing of each urinary bolus, as recorded by the different modalities was then compared. The results from 11 studies showed a significant correlation between the radioisotope and EMG methods (mean r = 1.00, P = 0.0003). There was a constant relationship between the part of the radioisotopic image representing the rear end of the bolus and the EMG complex (mean time difference = 5.32 +/- 1.067s), thus defining that part of the image representing the peristaltic contraction wave. There was a variable relationship between the EMG and the part of the image representing the leading edge of the bolus (mean time difference = 13.36 +/- 5.23s), emphasising that bolus length is variable, being dependent on bolus volume. The radioisotope "spindle" concurs with EMG activity in the porcine ureter. The compressed image technique is thus validated as a non-invasive method of demonstrating ureteric urine transport. PMID- 8461943 TI - New method for discriminating between calcium stone formers and healthy individuals. AB - A new method for discriminating between the urine of potential calcium stone formers and healthy persons has been proposed, based on determination of the calcium binding capacity of urine (CBC) by titration of early morning urine with a calcium chloride solution. For this purpose a new PVC matrix calcium ion selectrode for measuring calcium ion concentration in whole urine was used. The selectrode has a disposable membrane which can easily be prepared and replaced in the laboratory. Plots of the calcium ion concentration versus the concentration of total added calcium were linear up to a point where precipitation of calcium salts commenced. The slopes of these titration lines were used as criteria for discrimination. Statistical evaluation showed good separation between the urine of healthy and stone forming donors. A 2-sample t test with unequal variances gave mean values of 0.31 for healthy urine (13 samples) and 0.64 for stone forming urine (26 samples). Individual 99% confidence intervals were 0.21-0.40 for the controls and 0.54-0.73 for the patients respectively. Discriminant analysis showed that from a group of treated patients with low Dl (13 samples), 3 were classified as stone formers and 10 were non-formers. Thus there was good correlation with the clinical situation and with the previously proposed Dl test. PMID- 8461944 TI - Effect of Desmodium styracifolium-triterpenoid on calcium oxalate renal stones. AB - We have studied the inhibitory effects of Desmodium styracifolium-triterpenoid (Ds-t) (extracted from Desmodium styracifolium (Osbeck) Merr, a herbal medicine) on the formation of calcium oxalate renal stones induced experimentally by ethylene glycol (EG) and 1 alpha(OH)D3 (1 alpha D3) in rats. The incidence of urinary stone formation was 81% in the control group, which received EG and 1 alpha D3, and 29% in the Ds-t group, which received EG and 1 alpha D3 supplemented by Ds-t. The serum calcium (Ca) concentration in the Ds-t group was significantly elevated and urinary Ca excretion was markedly reduced. Urinary excretion of citrate (Cit), a factor that prevents stone formation, was significantly increased in the Ds-t group. Excretion of urinary phosphorus (P), which was elevated to a significantly greater extent in the controls than in the Ds-t group, was increased in both groups. The increase in urine volume in the Ds t group was significantly greater than in the control group. The 24-h creatinine clearance rate (Ccr) was significantly lower in the controls. These findings suggest that Ds-t inhibits the formation of Ca oxalate stones in rat kidneys by increasing the output of urine, decreasing the excretion of calcium and increasing the urinary excretion of citrate. Ds-t may be useful in preventing the recurrence of urinary Ca oxalate stones in the clinical setting. PMID- 8461945 TI - Is retrograde ureterography indicated in pelviureteric junction obstruction? AB - The role of retrograde ureterography in the management of pelviureteric junction (PUJ) obstruction remains controversial and it has recently been reiterated that visualisation of the entire ureter on the affected side is mandatory owing to the high incidence of other ureteric abnormalities. In a review of 119 consecutive adult pyeloplasties carried out over a 9-year period, only 2 ureteric abnormalities were found in association with PUJ obstruction (duplex ureter/3-cm proximal stricture). Other anatomical abnormalities included aberrant vessels, fascial bands and renal anomalies. Most secondary abnormalities were undiagnosed prior to surgery and all were easily dealt with per-operatively. PMID- 8461946 TI - Retrograde balloon dilatation for pelviureteric junction obstruction. AB - A total of 49 retrograde balloon dilatations for pelviureteric junction (PUJ) obstruction were carried out on 43 pelviureteric junctions in 42 patients from 1986 to 1991. The majority (34/43) were performed as primary treatment for PUJ obstruction, with 9 patients having a history of previous open pyeloplasty. Follow-up ranged from 3 months to 4 years (mean 18 months). Clinical improvement, as assessed by absence of symptoms, was seen in 34 cases (80%). There was either no change or an improvement in renographic findings (t1/2 time and/or split function) in 40 patients (93%). Of the 9 patients who were undergoing secondary treatment, 5 showed clinical improvement and 8 showed no change or renographic improvement. Nine patients required 12 further procedures, of which 5 were interval nephrectomy. Balloon pyelolysis is a simple procedure with good results over a 4-year follow-up period. It is less effective for the treatment of secondary pelviureteric junction obstruction. It has a low morbidity and no mortality, involves a short hospital stay and allows an immediate return to full activity. It is therefore an attractive alternative to open pyeloplasty as first line treatment for PUJ obstruction. PMID- 8461947 TI - Non-invasive investigation of normal individual ureteric activity in man. AB - This study was designed to investigate non-invasively human ureteric function between individuals and with increasing diuresis, using the radioisotope compressed image technique. Five normal males underwent fast frame renography with ureteric spindle imaging in dehydrated and hydrated states, urine production being measured in each individual for each scan. Urine flow rates and renographic parameters demonstrated that each ureter carried more urine in the hydrated state. The velocity at which individual boluses passed down the ureter was constant for each ureter and did not change with diuresis. The ureteric peristaltic rate showed wide individual variation between ureters in the same subject, but fell within what is becoming accepted as the "normal range" of < 4 urine boluses per minute. Some ureters accommodated an increase in urine flow by an increased peristaltic frequency, some showed no change and others showed a decreased frequency. In those ureters in which there was no change, or a decrease in peristaltic frequency with diuresis, the increased urine flow must have been handled by increases in bolus volume. Thus increases in ureteric urine flow in man are accommodated by changes in both peristaltic frequency and bolus size. The results are discussed in relation to previous studies which used invasive techniques. PMID- 8461948 TI - A combined urodynamic and continence unit--a review of the first 19 years. AB - We have completed a 19-year audit of all patients referred to the urodynamic/continence unit since its inception in 1972 and their subsequent clinical management; a total of 20,437 patients were referred, increasing from 51 in the first year to 1564 in 1990. Although the annual number of referrals has remained constant for the last 8 years, the need for more complex urodynamic assessment such as video-cystourethrography has increased from 5% (56/1164) in 1981 to 25% (385/1564) in 1990. The number of out-patient attendances to medical, physiotherapy and continence clinics has also increased over that period. We conclude that the number of referrals represents increasing recognition of the value of urodynamic assessment. Accurate diagnosis leads to more effective treatment, whether surgical, medical or conservative. Some methods of diagnosis are complex and suitable only for a tertiary referral centre. PMID- 8461949 TI - Bladder neck mobility evaluated by vaginal ultrasonography. AB - Factors involved in monitoring bladder neck mobility were studied by means of vaginal ultrasonography. Thirty-three continent, 28 incontinent and 39 patients who had undergone surgery for incontinence were examined in the supine and sitting positions during rest, the Valsalva manoeuvre and withholding urine. Bladder neck mobility can be described as a semicircular movement with the tip of the symphysis pubis as the centre and a line from the tip to the bladder neck as the radius (BS). Movement can be measured by 2 independent factors: BS distance and size of the angle between the BS line and the midline of the symphysis, at rest, during the Valsalva manoeuvre and withholding urine. The continent controls were characterised by a 90 degrees angle at rest, a long BS (2.4 cm) and a fixed bladder neck. The incontinent patients had a shorter BS (2.1 cm), angles at rest of approximately 100 degrees--the angle increased with the grade of incontinence- and a mobile bladder neck. If 2 of the 3 criteria (angle at rest > or = 95 degrees, BS < or = 2.3 cm and mobility > or = 20 degrees) are regarded as diagnostic of incontinence, diagnostic sensitivity was 84% and specificity 82%. In the surgical group, patients who failed to respond to treatment had a shorter BS, larger angles and greater bladder neck mobility than their successfully treated counterparts. PMID- 8461950 TI - Iatrogenic urogenital fistulae. AB - Nineteen patients with iatrogenic urogenital fistulae were treated between 1985 and 1989. All resulted from obstetric and gynaecological surgery. Major symptoms were leakage of urine through the vagina, menouria and perineal dermatitis. The fistulae formed after treatment for benign conditions in 18 patients. Fistulae complicating cancer surgery were uncommon. All patients with uretero-vaginal fistulae underwent preliminary percutaneous nephrostomy. Twelve patients underwent reconstruction using either the Boari-Ockerblad flap (5), uretero neocystostomy (4) or other techniques (3), all with excellent results. Most of the remaining patients had treatment elsewhere. We consider that preliminary diversion, followed by delayed reconstruction, is a valuable option in the management of uretero-vaginal fistulae. PMID- 8461951 TI - Peripheral blood lymphocyte response in patients with superficial transitional cell carcinoma of the bladder treated with intravesical Bacillus Calmette-Guerin- a useful marker of response? AB - Intravesical instillation of Bacillus Calmette-Guerin (BCG) offers safe and effective short-term/long-term treatment for superficial transitional cell carcinoma (TCC) and TCC in situ of the bladder. However, 17 to 42% of patients may experience recurrence in spite of this therapy and a marker of effective treatment is of paramount importance. In this study the in vitro response of peripheral blood lymphocytes (PBL) to BCG was analysed in 10 patients with superficial TCC and TCC in situ before and during BCG instillations. The in vitro response of PBL to BCG, expressed as a stimulatory index (SI), revealed that 6 patients had a SI > 5 and 4 patients had a SI < 5. None of the former patients had recurrence of TCC during a mean follow-up of 17 months, while all of the latter patients experienced recurrence of TCC within 9 months. It was concluded that the in vitro response of PBL to BCG may be used as a marker of response to intravesical BCG treatment. PMID- 8461952 TI - Mitomycin-C in superficial bladder cancer. Is long-term maintenance therapy worthwhile after initial treatment? AB - A total of 72 patients with recurrent superficial transitional cell carcinoma of the bladder (TCC) were treated with 40 mg intravesical instillations of mitomycin C (MMC) weekly for 10 weeks, followed by monthly maintenance doses. With a mean follow-up period of 41 months, 30 patients (42%) had a complete and sustained response after the initial treatment course, and a further 14 (19%) achieved a complete response on maintenance therapy. Sixteen patients (22%) continued to have recurrent tumours and the remaining 12 (17%) developed recurrent tumours after an initial complete response. Of these, 4 patients with carcinoma in situ (CIS) showed symptomatic improvement, but the histological changes persisted and all of those with tumours > 2 cm in size did not respond. We conclude that maintenance treatment with MMC is beneficial in superficial bladder cancer but is of limited value in the presence of bulky tumours or CIS. PMID- 8461953 TI - Two years' experience with photodynamic therapy of bladder carcinoma. AB - Eleven patients with intractable bladder carcinoma who were either unfit for radical surgery, or had refused it, were treated with whole bladder photodynamic therapy. Seven patients had carcinoma in situ and 4 had papillary tumours. Four of the 11 patients had recurrent tumours after a full course of radiotherapy for invasive bladder cancer. A complete local response was initially achieved in 9 patients with a mean follow-up of 12 months. The patients previously treated with radiotherapy had a remarkable response, with local control in all cases, but they had severe local side effects and a pronounced reduction in bladder capacity. In the non-irradiated group, bladder capacity was reduced permanently in only 1 of 7 patients. PMID- 8461954 TI - Expression of C-50 antigen as a prognostic variable in transitional cell bladder tumours. AB - The immunohistochemical expression of C-50 antigen was quantitated in paraffin embedded biopsy specimens of 218 transitional cell bladder tumours. The patients were treated according to standard practice in one institution and followed up for over 10 years. The expression of C-50 antigen was inversely correlated to T category, papillary status and WHO grade. Aneuploid tumours with a high S phase fraction (SPF) showed low expression of C-50 antigen. Progression in T, N and M categories was inversely correlated to CA-50 expression. Low expression of C-50 antigen predicted progression in Ta-T1 tumours. Expression of C-50 antigen was related to a favourable prognosis in the whole series, in papillary tumours, in diploid tumours, in WHO grade 2 tumours and in Ta-T1 tumours. The combination of DNA ploidy and expression of C-50 antigen was a highly significant predictor of survival. In Cox's analysis, expression of CA-50 had an independent predictive value in Ta-T1 tumours, whereas in the whole cohort the T category and papillarity were independent predictors. PMID- 8461955 TI - Cardiovascular reflexes in the neurological evaluation of impotence. AB - Testing of the autonomic cardiovascular reflexes (single breath beat-to-beat variation and orthostatic blood pressure change) was performed in 542 patients with erectile dysfunction who were grouped according to aetiological factors and their response to visual sexual stimulation and the papaverine test. Age-related normal values for autonomic tests were determined in the group of 124 patients with psychogenic impotence. Abnormal cardiovascular reflexes were associated with ageing and organic impotence, indicating autonomic dysfunction as a major contribution to impotence. Single breath beat-to-beat variation, as a simple non invasive test, is useful in the clinical evaluation of impotence, especially in patients with diabetes and a history of alcohol abuse. PMID- 8461956 TI - Extensive condylomata acuminata of male urethra: management by ventral urethrotomy. AB - Between 1982 and 1990, 4 males with extensive intraurethral warts presented with marked inflammation of the external genitalia. When sepsis had settled all patients underwent ventral urethrotomy, in which the urethra was divided median as far back as was necessary to expose all of the warts. Surgical and electro excision were the preferred methods of removal. Of 3 patients who developed recurrences 2 were lost to follow-up. A third remained without treatment for 1 year and when next seen the warts had spontaneously resolved and his urethra was closed. A fourth patient was lost to follow-up for 4 years before returning with destruction of his external genitalia by a verrucous carcinoma. The human immunodeficiency virus (HIV) did not appear to be a factor in the natural history of intraurethral warts in 2 patients who were negative for serum antibodies 2 and 8 years after presentation. PMID- 8461957 TI - The failed exstrophy closure: strategy for management. AB - In the last 7 years, 29 boys and 11 girls have been referred with failure of their exstrophy closure; 38 patients had classic bladder exstrophy and 2 had cloacal exstrophy. Reclosure was performed for complete bladder dehiscence in 28 cases and for significant bladder prolapse in 10. Two patients underwent revision of the posterior urethra after primary closure due to a severe urethral stricture secondary to the use of para-exstrophy skin flaps. Six patients underwent posterior iliac osteotomy at the time of initial bladder closure and in 34 no osteotomy was performed. Thirty-seven patients underwent either posterior iliac osteotomy (15) or anterior innominate osteotomy (22). Epispadias repair together with reclosure of bladder exstrophy was done in 20 boys. The upper tract has remained normal in all patients. Fourteen have undergone subsequent bladder neck reconstruction. Seven patients have undergone simultaneous bladder neck reconstruction and augmentation cystoplasty and 1 has undergone augmentation cystoplasty and Mitrofanoff procedure; all are dry on intermittent self catheterisation. The failed exstrophy reconstruction represents a formidable dilemma. However, a well planned reconstruction including osteotomy (even if previously performed), reclosure with or without epispadias repair or revision of the urethra can be performed with an excellent chance of proceeding with staged reconstruction. PMID- 8461958 TI - Efficacy and causes of failure of endoscopic subureteric injection of Teflon in the treatment of primary vesicoureteric reflux. AB - A total of 135 consecutive patients with primary vesicoureteric reflux (VUR) were treated as day cases using submucosal Teflon injection (STING) between 1984 and 1988. Up to 3 repeat procedures were performed in the event of failure; 89% of patients and 92% of ureters were cured. None was obstructed and 2 recurred. Eight patients continue to have asymptomatic reflux Grade 2 or less, while 7 have had open surgery to correct the reflux. Most of the failures had a satisfactory appearance at STING but this deteriorated with time and appears to have been caused by leakage of Teflon from the injection site post-operatively. There were no signs or symptoms of embolisation or migration of the implant material. PMID- 8461959 TI - GRAP repair: single-stage reconstruction of hypospadias as an out-patient procedure. AB - A novel repair of the distal urethra with glanular and preputial reconstruction is described for distal penile hypospadias; 52 consecutive patients underwent this procedure without catheter splintage or urinary diversion. All voided without problems on the day of operation; 44 (85%) were treated as day cases, while the remaining 8 boys stayed in hospital for at least 1 night post operatively for reasons not associated with the operation. Follow-up was complete and ranged from 15 to 30 months (mean 18). There was no evidence of meatal stenosis, phimosis or urethral stricture; 26 boys (50%) had associated chordee pre-operatively which was incompletely corrected in 2 (8%). These have a minor degree of chordee of glans on penile shaft and neither has required further treatment. Four boys (8%) developed partial wound breakdown which necessitated reconstruction in 2 and both of these have now been treated successfully. Functional and cosmetic results are excellent. PMID- 8461960 TI - Ileal conduit-enteric fistula. PMID- 8461961 TI - Reflex renal shutdown. PMID- 8461962 TI - Primary osteogenic sarcoma of the kidney presenting as staghorn calculus. PMID- 8461963 TI - Transitional cell carcinoma of the bladder in a young woman with the polycystic ovarian syndrome. PMID- 8461964 TI - Detrusor myopathy: a cause of detrusor weakness with retention. PMID- 8461965 TI - Colovesical fistula complicating unsuspected bladder outflow obstruction. PMID- 8461966 TI - Two cases of haemangiopericytoma. PMID- 8461967 TI - Re: Effect of vaginal ultrasound probe on lower urinary tract function. PMID- 8461968 TI - Familial Alzheimer's disease. A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine-->glycine). AB - Ten affected individuals are described from a kindred with autosomal dominant familial Alzheimer's disease in which a mutation in the amyloid precursor protein gene results in a valine to glycine substitution at amyloid precursor protein 717 which co-segregates with the disease. The mean age at onset of symptoms was 52 years with a range from 40 years to 67 years. The median duration of the disease was 11 years, with a range of 7-16 years. All individuals fulfilled the National Institute for Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. A homogeneous clinical and neuropsychological pattern was evident within the family. Myoclonic jerks, seizures, depression and a lack of insight were common features. Positron emission tomography demonstrated biparietal bitemporal hypometabolism in the one affected individual who was studied. The diagnosis was confirmed histopathologically in one individual. PMID- 8461969 TI - Normal and pathological saccadic dysmetria. AB - Initial saccades to visual targets are generally not precise in either normal subjects or patients with saccadic dysmetria. Quantitative criteria have to be applied to clearly distinguish between normal and pathological saccadic dysmetria, which is often found in patients with cerebellar lesions. To establish these criteria, the accuracy of visually guided horizontal saccades (10 degrees and 20 degrees target steps) was studied in a group of 24 patients with lesions affecting the cerebellum or its connections, and compared with data from 17 normal subjects. Eye movements were recorded with infrared oculography. Saccades of normal subjects had an average gain of 0.92-0.95 depending on the stimulus condition. Centripetal saccades were significantly larger than centrifugal saccades, for 20 degrees target steps. Most patients (n = 15) had significantly larger saccadic amplitudes than normal subjects (hypermetria), at least in one direction. Saccades in the opposite direction could be either hypometric, hypermetric or normal. Two patients had hypometric saccades in both directions. For one of the patients with hypermetria, in addition, the amplitude difference between centrifugal and centripetal saccades was significantly larger than in the normal subjects. Five patients had no significant pathology of the initial (primary) saccade, but a pathological pattern of corrective saccades. Two patients had normal saccades under all conditions. The quantitative comparison with normal subjects allows the detection even of mild pathology. According to our results, a pathology can be assumed when the average gain of saccades in at least one direction is 1.0 or more, or when more than two out of 20 saccades are followed by two corrective saccades of which the last is in the direction opposite to the initial saccade (pathological pattern of corrective saccades). Target steps of 20 degrees reveal a pathological condition more often than 10 degrees target steps. The application of quantitative criteria might be useful to establish a diagnosis of pathologic saccadic dysmetria even in instances in which it is clinically not obvious. PMID- 8461970 TI - Some saccadic eye movements can be delayed by transcranial magnetic stimulation of the cerebral cortex in man. AB - In 15 normal subjects we investigated the effect on visually guided saccadic eye movements of giving a single transcranial magnetic stimulus through a circular coil centered at the vertex. In the normal paradigm, subjects fixated a target which moved randomly to the left or right by 11 degrees. The mean saccadic reaction time of 189 ms was increased by 40-50 ms if a magnetic stimulus was given in random trials some 60 ms prior to the expected onset time of control saccades. The duration and amplitude of the saccades was unchanged. The delay was smaller if the stimulus was given earlier in the reaction period, or if the coil was moved anterior or posterior to the vertex. Larger stimulus intensities produced longer delays. Three subjects were trained to produce express saccades (mean saccadic reaction times of 107-141 ms) in a 'gap' paradigm. The latency of these saccades, which are thought to be mediated by collicular mechanisms without involvement of the cortex, was not affected by magnetic stimulation. This suggests that magnetic stimulation delays normal visually guided saccades by an action on the cerebral cortex, rather than on the oculomotor centres of the brainstem. Five subjects made non-targeted saccades in darkness in response to an auditory stimulus. These saccades, like visually guided saccades, could be delayed by magnetic brain stimulation. We conclude that saccadic delay is produced by interference with cortical areas involved in the execution of saccades rather than by interfering with the perception of the visual or auditory 'go' stimulus. These probably include supplementary and frontal eye field and posterior parietal cortex. The fact that visually guided saccades emerged intact after the delay indicates that the instructions for amplitude and direction were stored separately from those involved in timing when the movement was to occur. PMID- 8461971 TI - Motor recovery following capsular stroke. Role of descending pathways from multiple motor areas. AB - The functional anatomy of motor recovery was studied by assessing motor function quantitatively in 23 patients following capsular or striatocapsular stroke. While selective basal ganglia lesions (caudate and/or putamen exclusively) did not affect voluntary movements of the extremities, lesions of the anterior (plus caudate/putamen) or posterior limb of the internal capsule led to an initially severe motor impairment followed by excellent recovery, hand function included. In contrast, lesions of the posterior limb of the internal capsule in combination with damage to lateral thalamus compromised motor outcome. In experimental tracing of the topography of the internal capsule in macaque monkeys, we found axons of primary motor cortex passing through the middle third of the posterior limb of the internal capsule. Axons of premotor cortex (dorsolateral and post arcuate area 6) passed through the capsular genu, and those of supplementary motor area (mesial area 6) through the anterior limb. Small capsular lesion can therefore disrupt the output of functionally and anatomically distinct motor areas selectively. The clinically similar motor deficits with a similar course of functional restitution following disruption of these different descending motor pathways indicate a parallel operation of cortical motor areas. They may have the further capability of substituting each other functionally in the process of recovery from hemiparesis. PMID- 8461972 TI - Decrease of contralateral neglect by neck muscle vibration and spatial orientation of trunk midline. AB - Three patients with a right hemisphere lesion and marked left-sided neglect without visual field defects were asked to detect and identify stimuli which were tachistoscopically presented in the left or right visual half-field. Neglect of stimuli presented in the contralesional left visual field, which was observed when the patient's body was in a normal upright position with trunk, head and gaze oriented straight ahead to the middle of the projection screen, could be reduced by vibrating the left posterior neck muscles as well as by turning the trunk 15 degrees to the left. In contrast, unspecific stimulation on the left side of the patient's body, produced by vibrating the left hand muscles or the proprioceptive signal induced by turning the head 15 degrees to the left, had no compensatory effects. The results showed that the afferent information about real lengthening of the left posterior neck muscles (produced by turning the trunk) as apparent lengthening of these muscles (produced by their vibration), leads to a remission of contralateral neglect. Thus, the proprioceptive input from the neck muscles, i.e. the head-on-trunk signal, appears to influence the extension of the neglected part of space in patients with neglect. The signal seems to contribute substantially to the neural generation of the egocentric frame of reference that allows the determination of body position with respect to visual space. We hypothesize that the reduction of neglect by vibration of the contralateral posterior neck muscles is based on a shift of the subjective spatial localization of the sagittal midplane in the contralesional direction and a corresponding alteration of the egocentric coordinate system necessary for visuomotor coordination and exploration of space. PMID- 8461973 TI - Clinical responses to electrical brain stimulation of the temporal and frontal lobes in patients with epilepsy. Pathophysiological implications. AB - The clinical responses elicited by electrical stimulation of discrete cerebral structures in the temporal and frontal lobes were studied in 75 patients undergoing pre-surgical evaluation using chronic intracerebral electroencephalographic recordings. Responses without after-discharge spreading beyond the site of stimulation included somatosensory, autonomic, thermoregulatory and viscerosensory phenomena, simple motor responses, some simple automatisms, changes in facial expression or voice tone, vocalizations, conscious confusion and experiential phenomena. Except for oro-alimentary automatisms, these responses were similar to the initial responses elicited by stimulations followed by a spreading after-discharge. Responses were most often obtained from limbic structures, sometimes from the temporal isocortex, and rarely from frontal sites (except for simple motor activity and some simple automatisms). Specific clinical responses could often be elicited from more than one site (74 out of 147), frequently even from non-contiguous areas in the same or both hemispheres. This suggests that the neuronal substrates responsible for the production of some of these phenomena are widespread neuronal matrices linked through connections which have become strengthened through repeated use as hypothesized by one of us [Gloor (1990), Brain, 113, 1673-1694]. Such a hypothesis could also account for the individually idiosyncratic nature of many of these responses. PMID- 8461974 TI - Time course of action potentials recorded from single human afferents. AB - It was the object of this study to measure the time course of the action potential in individual human sensory nerve fibres in relation to conduction properties of the axons. For this purpose, the technique of percutaneous microneurography was combined with intradermal electrical stimulation of distal portions of the axons. Recordings were made at the wrist level from 57 type identified mechanoreceptive median nerve afferents [mainly rapidly adapting (RA) and slowly adapting type I (SAI)] innervating the glabrous skin of the hand. Measurements were made of the duration and time-to-peak of the positive peak of the diphasic (large positive phase followed by smaller, slower negative phase) action potential typically recorded using microneurography. Durations ranged from 0.31 to 0.75 ms (mean 0.50 ms) and times-to-peak from 0.12 to 0.45 ms (mean 0.21 ms), with no difference between afferent categories (RA, SAI). Time-to-peak was strongly positively correlated with duration (linear r = 0.81). Conduction velocity was measured over the distance extending from the point of intradermal stimulation (typically in the fingertips) to the point of recording at the wrist (distal conduction velocity). Absolute refractory period was measured using paired stimuli applied at the point of intradermal stimulation, within the receptive field of the afferent (distal absolute refractory period). Distal conduction velocities ranged from 15 to 60 m/s (mean 33 m/s), and distal refractory periods from 0.7 to 4.5 ms (mean 2.1 ms), with no difference between afferent types (RA, SAI). Distal absolute refractory period was inversely correlated with distal conduction velocity. The data were slightly better described assuming a non-linear (exponential) relationship; the non-linear correlation coefficient was -0.77. The time course of the action potential varied inversely with distal conduction velocity and directly with distal absolute refractory period. The time-to-peak versus conduction velocity data were slightly better described by a power than a linear relationship. Coefficients of correlation were: duration versus conduction velocity, linear r = -0.76; time-to peak versus conduction velocity, non-linear r = -0.64; duration versus absolute refractory period, r = 0.70; time-to-peak versus absolute refractory period, r = 0.76. Extensive intercorrelation between the variables duration, distal conduction velocity and absolute refractory period was revealed by multiple correlation techniques. Inter- and intra-subject skin temperature variation was within 5 degrees C. Correcting the time course, conduction velocity and absolute refractory period values for temperature variation within this limited range did not affect the results.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8461975 TI - Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review. AB - Neuromyotonia is a syndrome of spontaneously occurring muscle activity of peripheral nerve origin, which can be triggered by voluntary or induced muscle contraction. It is one among several causes of visible myokymia. Although neuromyotonia may sometimes accompany hereditary neuropathies, most cases are acquired. The abnormal activity is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high intraburst frequency, the frequency of the bursts themselves being irregular. Fibrillation potentials and fasciculations are often also present. We report five patients meeting these criteria. Clinical evidence suggesting a possible autoimmune aetiology included the presence of oligoclonal bands in the spinal fluid of the three patients examined and improvement following plasma exchange in two of three patients treated. Other supporting evidence from an English language literature review of approximately 40 patients reported in the last 20 years includes an associated thymoma in five cases, myasthenia gravis (two cases), raised anti acetylcholine receptor antibody titres (two cases) and induction by penicillamine (one case). Finally, two further patients have recently been reported to benefit from plasma exchange. These clinical data, taken together with the physiological changes observed in mice injected with patients' immunoglobulin G (reported separately), suggest that antibody-mediated autoimmune mechanisms, possibly directed to peripheral nerve K+ channels, may be important in the aetiology of acquired neuromyotonia. PMID- 8461976 TI - Vagolytic effect of diabetes mellitus. AB - The amplitude of respiratory sinus arrhythmia was quantified as the ratio of the longest to the shortest R-R intervals in electrocardiograms recorded during deep inspirations and forced expirations in the supine position. The mean of the absolute differences between consecutive R-R intervals recorded during normal quiet breathing in a supine position was also calculated. Since these two tests measure only cardiac parasympathetic function, they were used to assess the resting vagal tone in 165 patients with diabetes mellitus and 116 healthy volunteers (controls). The frequency distribution curve of resting vagal tone was Gaussian in the controls and was also negatively correlated with age and height. The frequency distribution curve of resting vagal tone was skewed in the diabetic population where a majority of patients had low vagal tone. The correlation of vagal tone with age was stronger than in controls, but there was no correlation of vagal tone with height in diabetic patients. The mean resting vagal tone in diabetic patients was reduced by 40%, and the whole frequency distribution curve was also shifted to the left by 40% relative to the control curve. It is concluded that there is a substantial impairment of cardiac vagal function in most diabetic patients, contrary to current belief. Clinical tests which include measurement of vagal tone may give a bias towards low values in diabetic patients because of the shift to the left in the distribution curve of vagal tone in the diabetic population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8461977 TI - Effect of locus coeruleus lesion on c-fos expression in the cerebral cortex caused by yohimbine injection or stress. AB - The injection of the alpha-2 adrenoceptor antagonist, yohimbine, has been shown to increase c-fos immunoreactivity in the rat cerebral cortex. To determine the extent to which this response is mediated by the central noradrenergic system, the present studies examined it in rats previously given unilateral 6-OHDA lesions of the locus coeruleus. The lesions were found to produce a significant attenuation of the response. A similar effect on the c-fos immunoreactive response to restraint stress was found. It is concluded that the noradrenergic system plays a necessary role in the above c-fos responses in the cortex to yohimbine and to stress. The c-fos protein therefore appears to be involved in the effects of noradrenergic neurotransmission in the CNS. PMID- 8461978 TI - HIV envelope protein-induced neuronal damage and retardation of behavioral development in rat neonates. AB - Cognitive and motor impairment are common symptoms among patients infected with the human immunodeficiency virus (HIV), including children who suffer neurological deficits and are frequently developmentally impaired. The HIV envelope protein, gp120, which has been shown to be toxic to neurons in culture, is shed in abundance by infected cells, and thus may play a significant role in the neuropathology of AIDS. To test this possible mechanism, neonatal rats were injected systemically with purified gp120 and the following consequences were observed: (1) radiolabeled gp120 and toxic fragments thereof were recovered in brain homogenates; (2) dystrophic changes were produced in pyramidal neurons of cerebral cortex; (3) retardation was evident in developmental milestones associated with complex motor behaviors. In parallel studies, co-treatment with peptide T, a gp120-derived peptide having a pentapeptide sequence homologous with vasoactive intestinal peptide, prevented or attenuated the morphological damage and behavioral delays associated with gp120 treatment. These studies suggest that gp120 and gp120-derived toxic fragments may contribute to the neurological and neuropsychiatric impairment related to HIV infection, and that peptide T appears to be effective in preventing gp120-associated neurotoxicity in developing rodents. PMID- 8461979 TI - Improving effect of acetylcholine receptor agonists on a deficit of 2 deoxyglucose uptake in cerebral cortical and hippocampal slices in aged and AF64A treated rats. AB - The aim of the present study was to determine whether the facilitation of 2 deoxyglucose (2-DG) uptake in the cerebral and hippocampal slices by nicotinic and muscarinic receptor agonists is compromised in the aged rat brain. For this, the effects of the nicotinic receptor agonist nicotine, the muscarinic receptor agonists oxotremorine and McN-A-343, and the ACh esterase inhibitors physostigmine and NK247 on 2-DG uptake in the brain slices of young (2-month-old) and aged (24-26-month-old) rats were tested. The decrements of 2-DG uptake in the cortical slices of aged rats were significantly attenuated by treatment with oxotremorine, nicotine and amiridine. In contrast, the metabolic responsivity of hippocampal slices to these drugs was reduced. To assess whether age-related changes in 2-DG uptake may be due to deficits in cholinergic function, we tested these drugs on the decrements of 2-DG uptake in ethylcholine aziridinium (a neurotoxic analog of choline) injected rats. The reductions of 2-DG uptake by injection of ethylcholine aziridinium was attenuated by oxotremorine but not by physostigmine. The present results reveal that metabolic decrements in the cerebral cortex from aged or ethylcholine aziridinium-injected rats were attenuated by muscarinic and nicotinic receptor agonists, suggesting that the muscarinic and nicotinic receptor mechanism in the cerebral cortex may be involved in cholinergic drug-induced functional recovery in aged rats. PMID- 8461980 TI - Immunocytochemical staining of neuropeptide Y (NPY) in the insular lobe of the monkey: a light microscopic study. AB - Neuropeptide Y (NPY) has been detected immunocytochemically in cerebral cortex and subcortical white matter of the primate frontal, parietal, temporal, and occipital lobes. Because little is known about NPY in the primate insular lobe and because peptides play an important role in normal neuronal functioning and alterations in brain peptides are associated with certain neurological diseases, we studied the presence, distribution, and structural characteristics of NPY immunostained elements at the light microscopic level in the insula of Macaca fascicularis. We used free-floating sections, rabbit anti-porcine NPY serum, and the avidin and biotinylated peroxidase complex technique. Neuropeptide Y immunostained neurons were demonstrated in layers II, III, and V/VI, and in the adjoining subcortical white matter. Immunostaining was localized to neuronal somata, neuronal processes, and a delicate plexus in the neuropil. The majority of NPY-immunostained neurons were non-pyramidal, had round somata 10-20 microns in major transverse diameter, and two or three neuronal processes. Computer-aided quantitative analysis of the length, breadth, and area of NPY-stained neurons was performed. Our findings are consistent with observations by others on the presence, laminar distribution, and structural characteristics of NPY immunostained elements at the light microscopic level in other cerebral lobes of non-human primates. PMID- 8461981 TI - A new method to study motoneuron regeneration using electromyograms shows that regeneration slows with age in rat sciatic nerve. AB - We developed a novel method for measuring motoneuron regeneration using transcutaneous electrical nerve stimulation to evoke electromyograms (EMGs). Using this technique we found that functional regeneration of the motoneurons of the rat sciatic nerve was significantly slower in 9-10-month-old rats (10 mo) than in 10-12 week old rats (3 mo). All rats received crush injuries of the sciatic nerve and were analyzed for reinnervation of the muscles in the foot by the novel EMG method on days 25, 29 and 33 post-surgery. There were significantly fewer test sites reinnervated in the foot of the older group. Fifty percent of the sites in the foot were reinnervated 27.2 days post-surgery in the 3 mo group in contrast to 33.7 days post-surgery in the 10 mo group, indicative of a 24% longer recovery period in the older animals. Rats were also assessed behaviourally with a behavioural test score (BTS). The BTS results correlated with the EMG findings demonstrating that our novel method measuring rate of recovery of EMGs is behaviourally relevant. We discuss the need to use animals older than 3 months for the study of 'adult' regeneration phenomena since 3-month old rats may be somewhat immature. We applied this age principle and the novel EMG method in our accompanying paper which shows the acceleration of nerve regeneration by weak DC electric fields. PMID- 8461982 TI - Weak electric current accelerates motoneuron regeneration in the sciatic nerve of ten-month-old rats. AB - When a weak direct current (DC) of 10 microA driven by an implantable device was applied to a crushed sciatic nerve in 9-10-month-old rats, regeneration was accelerated as assessed electrophysiologically. Rats underwent a sciatic nerve crush of the right leg and were randomly assigned to one of three groups: (i) Cathode Distal (CD); (ii) Sham Implant (SI); or (iii) No Implant (NI). On post operative days 25-39 each rat received a measurement of evoked electromyograms (EMG) in the foot. In addition each rat received a behavioural test score (BTS). This BTS correlated well with the evoked EMG results showing the behavioural relevance of the EMG results. NI rats performed the same as SI in the evoked EMG procedure, but CD rats performed significantly better than both the control groups. The recovery period in the CD rats was 21% shorter than in either the sham-treated or untreated controls showing that weak DC can greatly enhance nerve regeneration in adult rats. This result was in contrast to previous work in younger rats where DC treatments had no effects. The discrepancy is discussed in relation to the slowing of regeneration in older rats. PMID- 8461983 TI - Astrocytic and synaptic response to kindling in hippocampal subfield CA1. I. Synaptogenesis in response to kindling in vitro. AB - Early morphological events associated with the genesis of epileptiform activity are essentially unknown, despite significant progress on morphological correlates of potentially related plastic neural phenomena. Hippocampal area CA1 shows the capacity to generate epileptiform bursting activity after certain patterns of electrical stimulation. Using an in vitro slice kindling preparation, we found increases in the numbers (areal densities) of shaft and sessile spine synapses in hippocampal subfield CA1 within minutes following the establishment of stable afterdischarges. These data strongly suggest that synaptogenesis is associated with the early stages of epilepsy formation. PMID- 8461984 TI - Astrocytic and synaptic response to kindling in hippocampal subfield CA1. II. Synaptogenesis and astrocytic process increases to in vivo kindling. AB - Astrocytic glia are important for maintaining synaptic function during physiological activity. Recent hypotheses concerning epilepsy suggest a role for astrocytes in the control of neuronal excitability and in pathogenesis. This report provides morphological evidence that the periodic electrical stimulation used in the kindling model of epilepsy induces astrocytic hypertrophy and an increase in shaft synapse density in the CA1 region of the hippocampus. The Schaffer collateral pathway in the stratum radiatum of CA1 of five pairs of rats was kindled in vivo. Control animals received the same number of stimulations at a lower intensity and frequency. The animals were killed 24-48 h after reaching the criterion of five generalized seizures, and the brains were examined by electron microscopy. Kindling produced a 37% and 33% increase in the volume fraction of astrocytic processes in the middle and distal portions, respectively, of the s. radiatum in CA1. In the same tissue, the number (areal density) of shaft synapses was increased 25% in the s. radiatum of animals exhibiting generalized seizures. On the other hand, the areal density of degenerating synapses in both kindled and control animals was low and not significantly different. These results suggest that both synaptogenesis and hypertrophy of astrocytes contribute to an early stage of epileptogenesis when degenerative changes of the sort that might induce gliosis were not prominent in the tissue under study. PMID- 8461985 TI - Relationship between resting cytosolic Ca2+ and responses induced by N-methyl-D aspartate in hippocampal neurons. AB - Cytosolic calcium concentrations ([Ca2+]i) in cultured hippocampal neurons from rat embryos were measured using fura-2. Neurons with higher resting [Ca2+]i showed greater [Ca2+]i responses to N-methyl-D-aspartate (NMDA) and K+ depolarization. There was a strong relationship between resting [Ca2+]i and the maximal changes in [Ca2+]i (delta[Ca2+]i), which fit the our proposed equation to describe this relationship. PMID- 8461986 TI - Urinary 6-sulphatoxymelatonin excretory rhythms in laboratory rats: effects of photoperiod and light. AB - The excretion rhythm of the melatonin metabolite, 6-sulphatoxymelatonin, was determined in rats maintained on contrasting 14 h L:10 h D and 10 h L:14 h D photoperiods. The novel use of a high protein liquid diet together with an automatic urine collection system facilitated the monitoring of the onset, offset and total production of metabolite before, during and after a 57.5% reduction in the dark period (5.75 h and 8 h delay in lights off). In 14 L:10 D, melatonin metabolite excretion increased 2.7 +/- 0.2 h after lights off, whereas in 10 L:14 D, the onset occurred 5.1 +/- 0.2 h after lights off. Duration of melatonin metabolite excretion was not different between the two photoperiods. Reduction of the dark period by 57.5% delayed the appearance of melatonin metabolite excretion until 2.15 +/- 0.4h and 2.9 +/- 0.4h after darkness in both long and short photoperiods. Upon restoration of the original photoperiod on the third day, the onset of metabolite excretion was significantly delayed by 1.4 +/- 0.4 h (P < 0.05) in long day animals and 2.2 +/- 0.2 h (P < 0.05) in short day-length compared to the first day. This study highlights the utility of urinary 6 sulphatoxymelatonin determinations in rats and provides new information on the acute effects of extended evening light on pineal melatonin secretion. PMID- 8461987 TI - Rimmed vacuoles of inclusion body myositis and oculopharyngeal muscular dystrophy contain amyloid precursor protein and lysosomal markers. AB - Rimmed vacuoles are small areas of focal destruction of muscle fibres, found in inclusion body myositis, oculopharyngeal muscular dystrophy and other muscle disorders. They are known to contain amyloid proteins, probably of beta-amyloid type. We examined rimmed vacuoles immunohistochemically in 12 patients with inclusion body myositis and two patients with oculopharyngeal muscular dystrophy with antibodies to beta-amyloid precursor protein and cathepsin B and D. We found evidence for the presence of all these markers in rimmed vacuoles. These results confirm the presence of beta-amyloid in rimmed vacuoles, and provide additional support for the hypotheses that rimmed vacuoles are of lysosomal origin and that lysosomes are probably important in the metabolism of amyloid precursor protein. PMID- 8461988 TI - Involvement of amyloid precursor protein in memory formation in the rat: an indirect antibody approach. AB - The potential role of different isoforms of amyloid precursor proteins (APPs) in memory and learning processes was investigated in rats using antibodies differentiating between APP isoforms containing or lacking the Kunitz protease inhibitor (KPI) domain. Rats received intracerebroventricular injection of control immunoglobulins (IgGs), anti-KPI-APP (= anti-P3) or anti-N-terminus-APP (= anti-P4). No immediate effects on learning of a passive avoidance task were observed; however, performance evaluated 1 day later was somewhat impaired by the anti-P3 antibody (reacting with APPKPI) and even more markedly impaired by the anti-P4 antibody (reacting with both APP695 and APPKPI) relative to control antibody. The antibodies did not affect performance of an active avoidance task acquired prior to the experimental treatment or active avoidance learning 8 days post-treatment. These results suggest that blockade of APP by an antibody injected intracerebroventricularly impairs the consolidation and/or retrieval of memory in rats. PMID- 8461989 TI - The effect of dietary protein on thyrotropin-releasing hormone and thyrotropin gene expression. AB - In the rat, 48 h of food deprivation significantly reduces hypothalamic paraventricular nucleus (PVN) thyrotropin-releasing hormone (TRH) gene expression, anterior pituitary thyrotropin (TSH) gene expression and circulating triiodothyronine (T3). Using in situ hybridization histochemistry, we have now assessed the effect of selective nutritional deprivation, by comparing protein free and protein and fat-free diets with a normal diet matched for total energy content. As previously demonstrated, fasting markedly reduced PVN TRH transcripts, pituitary TSB beta transcripts, circulating T3 and body weight. Compared to rats fed a control diet, rats fed a protein-free or a protein and fat free diet of similar energy content showed a highly significant decrease in PVN TRH transcripts, pituitary TSB beta transcripts and circulating T3 levels. The exclusion of fat from the protein-free diet did not produce any further decline in the parameters measured. This indicates that variations in the protein composition alone of the diet are sufficient to reduce hypothalamic TRH mRNA, pituitary TSB beta mRNA and plasma T3, and are the predominant factors in the TRH response to starvation. PMID- 8461990 TI - Involvement of superoxide dismutase and glutathione peroxidase in attenuation of radiation-induced hyperthermia by interleukin-1 alpha in rats. AB - Pretreatment with recombinant human interleukin-1 alpha (rhIL-1 alpha) 20 h before irradiation attenuates radiation-induced hyperthermia. Experiments were conducted to determine the role of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) in rhIL-1 alpha-induced attenuation of radiation-induced hyperthermia. Radiation exposure increased SOD and decreased GSHPx levels in the hypothalamus, while treatment with rhIL-1 alpha increased GSHPx levels and had no effect on SOD levels. However, rhIL-1 alpha and irradiation together increased hypothalamic SOD level but prevented the fall in GSHPx level. Our results suggest that attenuation of radiation-induced hyperthermia by rhIL-1 alpha may involve stimulation of SOD and GSHPx because rhIL-1 alpha treatment and irradiation together increased hypothalamic GSHPx and SOD levels, and intracerebroventricular administration of SOD and GSHPx attenuated the radiation-induced hyperthermia. PMID- 8461991 TI - Calcium currents in pyramidal neurons acutely dissociated from the rat frontal cortex: a study by the nystatin perforated patch technique. AB - We studied electrical and pharmacological properties of voltage-activated Ca2+ currents (ICa) in freshly dissociated rat frontal cortical pyramidal neurons by using nystatin perforated patch and conventional patch-clamp techniques. With either nystatin perforated patch technique or conventional patch-clamp technique, low voltage-activated ICa (LVA ICa) and high voltage-activated ICa (HVA ICa) were recorded. However, in conventional whole-cell recording, HVA ICa ran down within 5-20 min, whereas the current remained stable for 50 min at least in nystatin perforated patch recording. The HVA ICa recorded by nystatin perforated patch technique was further classified to L-type, N-type and a current component resistant to both nicardipine and omega-conotoxin by their current kinetics, voltage- and drug-sensitivities. Present results suggest that the perforated patch technique is a useful method for studying the properties of high voltage activated Ca2+ channels. PMID- 8461992 TI - Effects of estrogen upon dopamine release from the corpus striatum of young and aged female rats. AB - In vitro superfusion was used to examine the effects of estrogen administration upon striatal dopamine release in ovariectomized young and aged female Fischer 344 rats in response to 10 microM amphetamine or 30 mM potassium stimulation. Estrogen treatment increased basal dopamine and decreased DOPAC release in young and aged females (10 micrograms estradiol benzoate given subcutaneously 24 and 48 h prior to superfusion). Amphetamine-stimulated dopamine release was significantly decreased in aged estrogen-treated females, but did not differ in young females as a function of estrogen treatment. Conversely, young females treated with estrogen showed significantly decreased striatal dopamine release in response to potassium stimulation, while aged females showed no differences as a function of hormone treatment. Striatal dopamine content was significantly decreased in all estrogen-treated young and aged females. It appears that estrogen is altering dopamine uptake mechanisms in both age groups, since basal DOPAC release is decreased and dopamine is increased. This estrogen effect depletes the readily releasable dopamine storage pool to a greater extent in the aged female as evidenced by reduced amphetamine-stimulated dopamine release. By contrast, estrogen does not alter vesicular dopamine storage pools in aged females, which are mobilized by potassium. These results may have important implications regarding sex differences in expression and treatment of age-related movement disorders. PMID- 8461993 TI - Gene delivery to spinal motor neurons. AB - This study demonstrates the direct delivery of plasmid gene constructs into spinal motor neurons utilizing retrograde axoplasmic transport. The plasmid vectors contained the Lac Z gene under the control of both the Rous sarcoma virus (RSV) and Simian virus (SV)40 promoters. beta-Galactosidase expression was observed in alpha and gamma motor neurons by histochemical staining following direct injection into the sciatic nerve or gastrocnemius muscle. The presence of LacZ gene constructs was confirmed by the polymerase chain reaction (PCR). The ability to introduce gene constructs into motor neurons allows for the study of gene regulation and permits the development of gene therapy strategies for motor neuron diseases including the spinal muscular atrophies (SMA) and amyotrophic lateral sclerosis (ALS). PMID- 8461994 TI - Neuroprotective activity of dimer of 16,16'-dimethyl-15-dehydroprostaglandin B1 (di-Calciphor) in cerebral ischemia. AB - Post-ischemic treatment of di-Calciphor (16,16'-dimethyl-15- dehydroprostaglandin B1) significantly improves animal survival and prevents ischemia-induced neurodegeneration of vulnerable forebrain regions assessed with histochemical and biochemical techniques in gerbils. Neuronal degeneration seen by Cresyl violet staining and silver impregnation in the CA1 sector of the hippocampus and the dorso-lateral sector of the striatum was significantly reduced in animals treated with di-Calciphor. In addition, the early onset of selective degradation of calpain I substrates spectrin and microtubule-associated protein (MAP2) in these same vulnerable regions was prevented. The lack of adverse side effects may facilitate the potential therapeutic use of this drug in preventing neuronal damage caused by stroke. PMID- 8461995 TI - Calcium-mediated metabolic stimulation of neuroendocrine structures by intraventricular endothelin-1 in conscious rats. AB - We examined the hypothesis that the vascular- and brain-derived peptide, endothelin-1 (ET), would affect cerebral neuroendocrine structures when administered via the peripheral circulation or via a lateral cerebral ventricle (i.c.v.). ET was infused intravenously (14 nmol/min) or injected i.c.v. (9 pmol) in conscious rats in which local cerebral glucose metabolism was assessed by the quantitative autoradiographic [14C]deoxyglucose technique. Whereas intravenously infused ET was previously demonstrated to selectively stimulate metabolic activity in the pituitary intermediate and anterior lobes of conscious rats, it was without effect in 20 individual structures or subnuclei involved in neuroendocrine functions, including several circumventricular organs. Intraventricular ET, however, caused hypermetabolic responses in 9 neuroendocrine structures, including the pineal gland, subfornical organ, median eminence, the hypothalamic paraventricular and supraoptic nuclei, and other hypothalamic and preoptic structures. The metabolic stimulation resulting from central ET was abolished or attenuated regionally by i.c.v. pretreatment with the calcium L channel inhibitor, nimodipine. The findings indicate that i.c.v. ET elicits a calcium-mediated hypermetabolic effect on several neuroendocrine structures in the forebrain involved in the regulation of fluid homeostasis, the cardiovascular system, and body temperature. PMID- 8461997 TI - Contribution of caudal ventrolateral medulla to the cardiovascular responses elicited by activation of bed nucleus of the stria terminalis. AB - The contribution of caudal ventrolateral medulla (cVLM) to the mean arterial pressure (MAP) and heart rate (HR) responses elicited by microinjections of L glutamate (GLU) into the cardiovascular responsive region of bed nucleus of the stria terminalis (BST) was investigated in the chloralose-anesthetized, paralysed and artificially ventilated rat. Unilateral injections of GLU into BST elicited decreases in MAP of -25 +/- 3 mmHg (n = 10) and HR of -13 +/- 3 bpm (n = 10). These cardiovascular responses were not altered after a 100 nl microinjection of 0.9% NaCl into cVLM. However, the magnitudes of the decreases in MAP and HR were attenuated (-11 +/- 3 mmHg and HR, -4 +/- 1 bpm, respectively) 5 min after a 100 nl microinjection of the reversible synaptic blocker cobalt chloride (CoCl2) into cVLM. Restimulation of BST 40 min after the 100 nl microinjection of CoCl2 in cVLM elicited cardiovascular responses that were not significantly different in magnitude from those evoked before the microinjection of CoCl2 (MAP, -23 +/- 4 mmHg; HR, -12 +/- 5 bpm). In an additional series of experiments (n = 3), restimulation of BST 1 h after an ipsilateral electrolytic lesion in cVLM elicited decreases in MAP (-11 +/- 2 mmHg) and HR (-8 +/- 4 bpm) that were significantly smaller than those elicited prior to cVLM lesion. These data suggest that a component of the pathways originating in BST involved in mediating depressor responses and cardiac slowing relays in cVLM. PMID- 8461996 TI - Evaluation of role of upper cervical inspiratory neurons in respiration, emesis and cough. AB - Upper cervical (C1-3) inspiratory (UCI) propriospinal neurons project to spinal segments containing respiratory motoneurons, but their functional significance is unknown. Bilateral kainic acid injections into this cell column in 12 decerebrate cats (11 paralyzed and artificially ventilated) had no major effect on phrenic, intercostal, and abdominal nerve discharge or EMG activity during (fictive) respiration, vomiting and coughing. Thus, UCI neurons are unessential for activation of major respiratory muscles during these behaviors. PMID- 8461998 TI - Microdialysis analysis of norepinephrine levels in the paraventricular nucleus in association with food intake at dark onset. AB - It has been proposed that norepinephrine (NE) in the paraventricular nucleus (PVN) acts to stimulate carbohydrate feeding specifically at the start of the active (dark) cycle in rats. This study used microdialysis to examine the relationship between endogenous levels of NE in the PVN at dark onset and the amount of food consumed at this time. The results indicated that: (1) in satiated rats on a lab chow diet, NE levels in the PVN, as opposed to sites anterior or lateral to this nucleus, were significantly higher during large meals around dark onset then they were during small meals or during intervals that preceded the large meals, and (2) in food-deprived animals given a pure carbohydrate diet at dark onset, PVN levels of NE just before the initiation of the meal were significantly higher in animals that consumed a relatively large carbohydrate meal (> 2.0 g) during the first dark hour, and they were significantly correlated across animals with the size of their carbohydrate meal. These findings are consistent with other evidence linking endogenous PVN NE to food intake at the beginning of the natural feeding cycle. PMID- 8461999 TI - Antidromic activation of a peptidergic pathway in the limbic system of the male rat. AB - Stimulation of the medial amygdaloid nucleus (AME) produces a long-latency and long-lasting inhibition of pyramidal cells in both the dorsal and the ventral hippocampus. The inhibition is blocked by a specific antagonist to vasopressin, which is a candidate neurotransmitter in the system. Antidromic activation of the AME from the hippocampus occurs with a latency suggestive of the conduction velocity of small diameter unmyelinated fibers. Immunocytochemistry for vasopressin reveals small diameter, unmyelinated immunoreactive fibers in the vicinity of the stimulating electrode in the hippocampus, and immunoreactive cell bodies in the vicinity of the recording electrode in the AME. PMID- 8462000 TI - Synaptic connections of a periodontal primary afferent neuron within the subnucleus oralis of the cat. AB - The central axon of a primary afferent neuron that responded to light mechanical stimulation of the lower premolar teeth in a fast adapting fashion was intra axonally injected with horseradish peroxidase in the cat. The labeled terminals within the rostrodorsomedial (Vo.r) and dorsomedial (Vo.dm) parts of subnucleus oralis were examined electron microscopically. The labeled ending had pale axoplasm, contained clear spherical synaptic vesicles, and formed multiple synapses with dendrites and/or unlabeled axonal endings with pleomorphic vesicles (P-endings). In these synaptic contacts, the labeled primary ending was presynaptic to dendrites and postsynaptic to P-endings. Labeled endings simultaneously synapsing with both dendrites and P-endings were more frequent in Vo.dm (28%) than in Vo.r (8.3%). PMID- 8462001 TI - A new soluble brain-specific protein: identification and partial purification. AB - A new soluble 170-kDa protein (BP170) was found to be present exclusively in the brain of all the vertebrates that we studied by Western immunoblotting. It was not detected in peripheral rat tissues, including heart, kidney, liver, spleen, lung, muscle, adrenal, intestinal mucosa, sciatic nerve, or pituitary. In rat brain, its regional distribution was found to be heterogeneous, with its highest concentration in the cerebrum and its lowest in the hypothalamus, and 89% of it was in the post-microsomal fraction. BP170 constitutes at least 0.05% of the total brain cytosol proteins. Its level increases during development, being the lowest at 5 days and the highest at 90 days postnatal. BP170 is a single-chain polypeptide. It could be partially purified by precipitation with polyethylene glycol followed by column chromatography on Q Sepharose. Although BP170 was identified by an antiserum against puromycin-sensitive aminopeptidase (PSA), the two proteins differ in molecular weight, chromatographic properties, regional and subcellular distribution, developmental changes, immunoreactivity, and enzyme activity. Self-incubation or trypsin treatment of the partially purified BP170 generates no PSA activity, indicating that BP170 is not a PSA precursor. Furthermore, BP170 is neither an inhibitor nor an activator of PSA. Our data suggest that BP170 is a novel brain-specific protein not previously described. PMID- 8462002 TI - Angiotensin II decreases the rate of production of cerebrospinal fluid. AB - The choroid plexus, which produces cerebrospinal fluid (CSF), contains receptors for angiotensin II and a very high concentration of angiotensin-converting enzyme. Circulating angiotensin II decreases blood flow to the choroid plexus. The first goal of this study was to examine the hypothesis that angiotensin II decreases the production of CSF. The second goal was to determine whether effects of angiotensin II on the production of CSF were receptor-mediated. Production of CSF was measured in chloralose-anesthetized rabbits using ventriculocisternal perfusion of artificial CSF containing blue dextran. Rabbits received either vehicle, angiotensin II, angiotensin II in the presence of an angiotensin II antagonist (saralasin), or saralasin intravenously. Increases in blood pressure, during administration of angiotensin II, were prevented by withdrawal of blood. Under control conditions, CSF production averaged 7.2 +/- 0.2 microliters/min (mean +/- S.E.). Angiotensin II (100 ng/kg/min i.v.) decreased CSF production by 24 +/- 3% (P < 0.05, n = 8). In the presence of saralasin (1 microgram/kg/min i.v.), angiotensin II had no significant effect on CSF production (-4 +/- 6%, P > 0.05, n = 7). Vehicle did not affect CSF production significantly (-2 +/- 6%, P > 0.05, n = 7). Saralasin alone decreased production of CSF (-21 +/- 5%, P < 0.05, n = 7). To test the specificity of saralasin in blocking effects of angiotensin II receptor stimulation on CSF production, the carbonic anhydrase inhibitor acetazolamide was administered in the presence and absence of saralasin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462003 TI - Increased sensitivity of the hippocampus in ethanol-dependent rats to toxic effect of N-methyl-D-aspartic acid in vivo. AB - Chronic administration of ethanol in animals leads to CNS tolerance and physical dependence. Subsequent withdrawal of ethanol causes hyperexcitability which is thought to be related to increased sensitivity of N-methyl-D-aspartic acid (NMDA) receptors. The purpose of this study was to investigate sensitivity to NMDA in ethanol-treated animals by detecting damage after intrahippocampal injection of NMDA. Choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) specific activity was used as markers of cholinergic and gamma-aminobutyric acid neurons, respectively. Ethanol-dependent animals were more liable to die following intrahippocampal injection of either 120 or 240 nmol of NMDA. There was a significantly greater decrease in hippocampal GAD but not ChAT specific activity in the surviving animals. These data support the hypothesis that ethanol dependence is associated with increased sensitivity to NMDA which may be responsible for excitotoxic brain damage and death. PMID- 8462005 TI - Electrophysiological characterization of the projection from the nucleus raphe magnus to the lateral reticular nucleus: possible role of an excitatory amino acid in synaptic activation. AB - Numerous studies have shown that the lateral reticular nucleus (LRN), located in the caudal ventrolateral medulla, is an important nuclear region in the descending analgesia system. Activation of this brainstem region, either electrically or chemically, results in a reduction in nociceptive threshold. In addition, destruction of LRN abolishes the tonic descending inhibition present on dorsal horn neurons. Recent neuroanatomical tracing studies have shown that the nucleus raphe magnus (NRM), long implicated in nociception, sends direct projections to LRN; however, no information exists regarding the physiological characteristics of this pathway, nor its role in the endogenous descending analgesia system. The purpose of this study was to physiologically characterize the synaptic influence(s) of projections from the NRM to the LRN using electrophysiological recording, electrical and chemical stimulation, and iontophoretic techniques. Sixty-one percent of LRN neurons responded to single pulse stimulation of NRM; 52% of the responsive cells were excited and 48% were inhibited. The mean latency to onset of excitation was 4.9 +/- 1.2 ms. High frequency (100 Hz) electrical stimulation of NRM influenced 69/102 neurons; 52% (36/69) were excited, while 48% (33/69) were inhibited. Microinjection of glutamate into NRM significantly modified the discharge of 83% (93/112) of LRN cells tested; of these, 71% were inhibited, while 29% were excited. In 35 cells the effects of the excitatory amino acid antagonist kynurenic acid (KYN) were studied. In 75% of the cells excited by glutamate administration into the NRM (18/24), KYN partially antagonized this response. In 11 LRN cells inhibited by NRM chemical stimulation, KYN had no effect on this inhibition. Overall, 95% of the LRN cells responsive to NRM stimulation were also responsive to noxious peripheral stimulation, indicating that these cells are receiving ascending information from the spinal cord regarding somatosensory stimulation as well as receiving descending input from the NRM. It is concluded that LRN neurons are highly responsive to both noxious peripheral stimulation and NRM efferent activation, and that this region plays a significant role as an integrator for both ascending and descending information. PMID- 8462004 TI - Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. AB - CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity. PMID- 8462006 TI - Distribution of fibroblast growth factor 5 mRNA in the rat brain: an in situ hybridization study. AB - Fibroblast growth factors (FGFs) are potent growth factors with roles in the brain ranging from development to adult plasticity. FGF-5 is a newly described member of the fibroblast growth factor family. In order to evaluate a possible role of FGF-5, we have examined the locus of synthesis of FGF-5 in the rat brain. We have used in situ hybridization of 35S-labelled RNA probe complementary to FGF 5 mRNA. FGF-5 mRNA was present in neurons in select regions of the rat brain. FGF 5 mRNA expression was particularly intense in the olfactory bulb within periglomerular elements and the mitral cell layer. The primary olfactory cortex also showed a robust expression of FGF-5 mRNA mostly within layer II. In the hippocampal formation, the greatest labelling of FGF-5 mRNA occurred in hippocampal pyramidal cells within subfields CA3 and secondarily within subfields CA1, CA2 and CA4. The dentate gyrus granule cells displayed a modest hybridization signal. The cerebral cortex (neocortex) showed a light labelling throughout its rostro-caudal extent mostly within external layers. The entorhinal cortex showed a higher FGF-5 mRNA expression as compared to the neocortex and signal appeared more intense in layer II. In general, FGF-5 mRNA was shown to be localized mostly in limbic structures, suggesting that FGF-5 may play a role in limbic system function or dysfunction. PMID- 8462007 TI - Long-term potentiation of perforant path synapses in hippocampal CA1 in vitro. AB - This paper reports a study of long-term potentiation (LTP) of perforant path synapses in CA1. Using rat hippocampal slices with CA3 and the dentate gyrus removed, stimulation of the perforant path evoked a population excitatory postsynaptic potential (pEPSP) that was negative-going in s. lacunosum-moleculare of CA1. High-frequency conditioning stimulation of the perforant pathway induced LTP of the perforant path pEPSP in slices disinhibited by the GABAA receptor antagonist bicuculline methiodide (20 microM). Conditioning of the perforant pathway in normal medium, however, failed to induce LTP. Potentiation of the perforant path pEPSP in the presence of bicuculline lasted at least 1 h, was specific to the tetanized pathway, and based on a threshold property, appeared associative in nature. PMID- 8462008 TI - Serotonergic influence from nucleus raphe obscurus on neurones in the periaqueductal grey matter in the rat. AB - In rats anaesthetised with urethane, iontophoretic application of 5 hydroxytryptamine (5-HT, 5-70 nA) produced changes in ongoing activity of 41/44 neurones in the periaqueductal grey matter (PAG). The majority (85%) of responsive cells were inhibited and 15% were excited. The inhibitions were mimicked in 5/7 cells by iontophoresis of the 5-HT1A agonist 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT, 10-30 nA) whilst excitation was produced in 3/5 cells by iontophoresis of the 5-HT2 agonist alpha-methyl-5-HT (10-30 nA). Selective activation of neuronal perikarya in nucleus raphe obscurus (NRO) by microinjection of 50-100 nl D,L-homocysteic acid (DLH) inhibited ongoing activity of 25/31 neurones tested in the PAG for periods of 30-580 s, mean 183.5 s. The duration of the inhibition was potentiated by between 36 and 300% during iontophoresis of the 5-HT re-uptake blocker paroxetine (1-25 nA, 6/6 cells). The results indicate that there is an extensive inhibitory serotonergic input to the PAG which originates, at least in part, from NRO. PMID- 8462009 TI - Dopamine release from canine striatum following global cerebral ischemia/reperfusion. AB - The elevation of extracellular dopamine (DA) levels in the striatum of experimental animals subjected to ischemic insult has been well documented. The contribution of excessive DA to neuronal damage can be inferred from the ability of DA antagonists, as well as selective destruction of dopaminergic tracts, to confer neuroprotection in models of ischemia. In the current study, we report an enhanced releasability of preloaded [3H]DA in response to either elevated potassium or N-methyl-D-aspartate (NMDA) from striatal slices of beagles that had experienced 10 min of ischemia induced by cardiac arrest. The elevation in sensitivity to potassium stimulation was transient, approaching control levels after 30 min of reperfusion. In contrast, release stimulated by NMDA was elevated immediately after cardiac arrest and remained elevated for as long as 24 h of reperfusion. Release stimulated by NMDA was enhanced by glycine (Gly) and inhibited by MK801, consistent with mediation through the NMDA receptor/channel complex. The increased sensitivity of DA release, coupled with the high levels of excitatory amino acids (EAAs), including glutamate (Glu), aspartate (Asp) and Gly in ischemic brain, probably contribute to the extensive neuronal cell damage. PMID- 8462010 TI - Conventional versus high-dose epidoxorubicin as single agent in advanced breast cancer. AB - Between March 1986 and December 1987, two groups of consecutive patients with advanced breast cancer underwent epidoxorubicin (Epidx) monochemotherapy. Twenty three patients (group A) received Epidx at a dose of 60 mg/m2 and 27 (group B) at a dose of 120 mg/m2 (i.v. every 3 weeks). No patient had undergone anthracycline treatment before entering the study. Age ranged from 39 to 70 years (mean 52) in group A and from 35 to 69 (mean 50 in group B). The main sites of involvement were liver (5 patients in group A and 10 in group B), lung (4 and 5 patients, respectively), bone (7 and 8 patients, respectively), and soft tissue (6 and 5 patients, respectively). The number of courses of therapy ranged from 4 to 10 (mean 7.4) in group A and from 3 to 10 (mean 6.6) in group B. Tumor response and toxic effects were graded according to World Health Organization criteria. CR + PR were 35% in group A and 67% in group B (chi square = 3.862, p < 0.05). Results were analyzed at 130 weeks from the beginning of the therapy. At this time, survival was 9% in group A and 15% in group B, with a median survival time of 61 weeks (range 18-130) and 77 weeks (range 24-130), respectively. No patient in group A showed cardiac toxicity higher than grade 2 during or after the treatment, whereas in group B, 2 patients developed congestive heart failure after a cumulative Epidx dose of 1080 and 1200 mg/m2. Treatment delays, to allow recovery of white blood cells, were infrequent and occurred only in patients previously subjected to chemotherapy. No patient required hospitalization for sepsis, and alopecia was reversible in all patients. Our data demonstrate that there is a relationship between Epidx dose and response rate in advanced breast cancer. PMID- 8462011 TI - Colonic epithelial proliferation indices before and after colon cancer removal. AB - Rectal mucosal (epithelial) proliferation labeling indices (LI) have been widely used as a risk marker for colorectal cancer and as an intermediate end-point in chemoprevention studies. The purpose of this study was to determine whether the presence of cancer preoperatively altered the LI and whether these LI could be used over the long term as a marker for colon cancer. We studied 25 patients (18 with colorectal cancer and 7 with benign colonic diseases) who were admitted for colonic resection. Biopsies for thymidine LI were taken before, during, and 4 and 7 months after the operation. The preoperative LI of cancer patients was higher, but not significantly, than that of noncancer patients (5.22 +/- 3.54 and 4.11 +/ 1.34%, respectively, p = 0.28). The intraoperative LI was significantly higher than the preoperative LI (8.08 +/- 4.00 and 4.90 +/- 3.07%, respectively; p = 0.004). After 4 and 7 months, the LI was not significantly different from the preoperative LI (p = 0.60 and 0.89, respectively). Resection of a colonic segment did not affect the level of proliferation over time. Therefore, it is unlikely that LI can be used as a marker to predict local recurrence after curative resection of colorectal cancer. PMID- 8462012 TI - Effect of blood-brain barrier and blood-tumor barrier modification on central nervous system liposomal uptake. AB - In this study of 25 central nervous system (CNS) tumor-bearing rats, the CNS biodistribution of intravenously administered, indium-labeled liposomes was investigated. In 16 animals, the blood-brain barrier and blood-tumor barrier were modified using intracarotid administration of etoposide. In control animals, analysis by autoradiography and well-counting experiments demonstrated uptake of liposomes in the tumor-bearing hemisphere (% injected dose/g tissue = 0.135) with minimal uptake in the non-tumor-bearing hemisphere (% injected dose/g tissue = 0.007), p < 0.01. Unilateral intracarotid etoposide administration enhanced liposome uptake in both hemispheres-0.215 and 0.023 (tumor-bearing and nontumor bearing), respectively. The presence of meningeal tumor involvement in nontumor implanted hemispheres increased liposomal uptake 10-fold. These findings may have clinical applicability in designing therapeutic protocols for the treatment of CNS tumors. PMID- 8462013 TI - Radioimmunodetection of colorectal cancer metastases with 131I-labeled monoclonal antibody B72.3: a pilot study to determine efficacy of detection and pharmacokinetics. AB - We performed radioimmunoscintigraphy (RIS) and/or pharmacokinetic (PCK) studies in 12 patients with primary or metastatic colorectal carcinoma, utilizing an intravenous administration of 1-4 mCi (1 mg) of 131I-B72.3 monoclonal antibody. Metastatic lesions were correctly identified in 4/8 patients by RIS. Two patients with small lesions (> 2 cm diameter) had a false-negative RIS scan. Two patients had a true-negative RIS scan. Optimal images were obtained at 1 week postinjection. PCK studies showed that the plasma clearance of 131I-B72.3 was biexponential with an alpha-phase half-life ranging from 0.5 to 7.1 hr and a beta phase half-life ranging from 47.5 to 85.3 hr. Systemic and renal clearance data indicated that 131I-B72.3 was cleared very slowly and almost entirely by deiodination. This pilot study was conducted to gain an understanding of the pharmacokinetics of this radiolabeled antibody. On the basis of these data, we are now studying second-generation antibodies as part of our long-range objectives to incorporate them in early detection and treatment protocols. PMID- 8462014 TI - Epirubicin and ifosfamide in advanced soft tissue sarcoma: a phase II study. AB - Thirty patients with previously untreated and measurable or evaluable advanced soft tissue sarcoma entered this phase II study. Median age was 53 years (range: 24-71 years). Starting dose of Epirubicin was 100 mg/m2 IV bolus on day 1 combined with Ifosfamide, 2.5 g/m2, as a 6-hr IV infusion on day 1 and day 2 with uroprotection with Uromitexan, 1.6 g/m2, on day 1 and day 2. This schedule was repeated every 3 weeks. In case of minimal myelosuppression, the dose of Epirubicin was increased by 10 mg/m2 up to 130 mg/m2. Ifosfamide dosage was not increased. Mean cumulative dose of Epirubicin received was 477 +/- 272 mg/m2 (range: 200-1200 mg/m2). Of 27 evaluable patients (WHO criteria), 13 had a partial response (48%), 4 showed no change (15%), and 10 had progressive disease (37%). Median time to progression was 27 weeks. Of 27 patients evaluable for toxicity, hematological toxicity at day 21 was mild. Nonhematological toxicities consisted of nausea and vomiting in 82% of patients (WHO grade 3-4 = 19%), stomatitis in 44.5% (WHO grade 3 = 7.5%), and alopecia in 96% (WHO grade 2-3 = 89%). Appearance of cardiac dysfunction without heart failure during the treatment led to discontinuation of this chemotherapy in 3 patients. The results of this study show that the combination of Epirubicin and Ifosfamide is effective in advanced soft tissue sarcoma with an acceptable toxicity. However, we cannot conclude from this trial whether combination Epirubicin and Ifosfamide is superior to Epirubicin alone. PMID- 8462015 TI - Strategies to improve continuity of care and decrease rehospitalization of cancer patients: a review. PMID- 8462016 TI - Pap smears, elderly women, and Medicare. PMID- 8462017 TI - Continuous intravenous narcotic infusions for cancer pain. PMID- 8462019 TI - Patient awareness under general anesthesia. PMID- 8462018 TI - Concepts of antibody-mediated cancer therapy. PMID- 8462020 TI - Functional significance of c-myb expression in normal and leukemic hematopoiesis. PMID- 8462022 TI - Clinical results with recombinant human interleukin-3. PMID- 8462021 TI - Modulation of cytotoxicity and differentiation-inducing potential of arabinofuranosylcytosine in myeloid leukemia cells by hematopoietic cytokines. AB - Hematopoietic growth factors may be useful in improving the clinical effectiveness of arabinofuranosylcytosine (ara-C). In vitro studies have indicated that interleukin 3(IL-3) and, to a lesser extent, granulocyte macrophage colony-stimulating factor (GM-CSF), but not G-CSF or M-CSF, may be capable of specifically augmenting the ability of ara-C to kill leukemic myeloid cells by pharmacological and cytokinetic mechanisms including increase of intracellular ara-CTP/dCTP pool ratios and enhanced ara-C DNA incorporation in leukemic blast cells, decrease of IC 90 of ara-C for leukemic colony-forming cells (CFC) as compared with normal CFC growth, and recruitment of quiescent leukemic cells into the cell cycle. In contrast, the combination of ara-C with M CSF or with the leukemia inhibitory factor (LIF) appears to be useful in overcoming the block in differentiation of leukemic blast, while the effects of GM-CSF and IL-3 on ara-C-induced differentiation appear limited. The combined treatment of human myeloid leukemia cells by ara-C and LIF is associated with down-regulation of c-myc gene expression, transcriptional activation of jun/fos gene expression, and features of functional differentiation (e.g., the capability to reduce nitroblue tetrazolium, to express lysozyme, or to display differentiation-related surface receptors including C3bi and the c-fms protein). On the basis of these in vitro studies first clinical trials are underway that are examining the efficacy of ara-C combinations with these molecules for the treatment of myeloid disorders. PMID- 8462023 TI - The use of recombinant human granulocyte macrophage colony-stimulating factor in autologous and allogeneic bone marrow transplantation. AB - In order to determine the effect of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF), it has been administered to patients undergoing autologous or allogeneic bone marrow transplant (BMT). Results in patients undergoing autologous or allogeneic BMT indicate that rhGM-CSF is minimally toxic and is associated with reduced morbidity. Trials also indicate that rhGM-CSF may be an acceptable therapy for patients with marrow graft failure since survival appears to improve substantially in patients who received rhGM-CSF compared with historical control patients. PMID- 8462024 TI - Combination treatment of acute myeloblastic leukemia with rhGM-CSF and standard induction chemotherapy. PMID- 8462025 TI - A model for others: a strategy for improving diagnosis and therapy of human malignancies using monoclonal antibodies targeting TAG-72 oncofetal antigen. PMID- 8462026 TI - Severe 5-fluorouracil toxicity in a patient with decreased dihydropyrimidine dehydrogenase activity. PMID- 8462028 TI - Body composition and bone mineral distribution during growth in females. AB - The total mass of lean tissue, fat and bone mineral was measured in a cross sectional study by dual-photon absorptiometry in 76 normal, ambulatory females aged 8 to 26 years. These measurements allowed quantification of average total body bone mineral density and assessment of the mass and the average density of bone mineral in different regions of the body, specifically the head and the legs. Both total-body and regional results are presented as logistic functions of age; the functions were derived by nonlinear regression analysis. Normal ranges, defined as twice the root mean square deviation about the fitted equation, are also expressed as functions of age. As well as providing normal reference values, these data suggest that muscle mass is an important determinant of total-body bone mineral mass and that peak bone mass is achieved at different ages in different regions of the skeleton. PMID- 8462027 TI - Long-term follow-up of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and possible postoperative radiotherapy and/or chemotherapy in squamous cell carcinoma of the esophagus. AB - Seventy patients with local squamous cell carcinoma of the esophagus were treated between 1981 and 1990 with preoperative chemotherapy, surgical resection, and possible postoperative radiation therapy and/or chemotherapy. Chemotherapy included two cycles of 5-fluorouracil (1000 mg/m2) by continuous intravenous infusion on days 1-4 and cisplatin (100 mg/m2) on day 4. Complete clinical response (CCR) was achieved in 28 (41%) patients, partial clinical response (PCR) in 17 (25%), and no response in 23 (34%). Fifty-five (81%) patients were resected, 6 (9%) were explored, and 7 (10%) were unable to have surgery. Microscopic analysis of 55 resected patients showed 50 (91%) with active tumor, 1 (2%) with necrotic tumor, and 4 (7%) with a pathological complete response to chemotherapy. Twenty-six of the 55 resected patients (47%) had no gross evidence of disease at the time of surgical inspection. Median overall survival was 21.86 months (range 2-107 months) for all patients and 26.71 months (range 2-107 months) for resected patients. Actuarial 5-year survival rate was 31% for all patients and 39% for resected patients. Prolonged survival correlates with complete clinical response to chemotherapy, low pathological stage of disease, and successful resection of the lesion. PMID- 8462029 TI - Computed tomography during arterial portography in malignant carcinoid syndrome: a report of two patients. AB - Computed tomography during arterial portography (CTAP) and delayed high-dose iodine computed tomography (CT) have improved the preoperative localization of hepatic metastases from colon cancer. Nearly all patients presenting with malignant carcinoid syndrome have liver metastases, and removal of tumour bulk is considered the most effective means of management. To determine suitability for hepatic resection, CTAP and delayed high-dose iodine CT were used to evaluate the distribution of hepatic disease in two patients with malignant carcinoid syndrome. In both patients CTAP showed lesions not seen during recent dynamic incremented CT; the location of the lesions precluded resection. CTAP also demonstrated metastases less than 1 cm in diameter in one patient. Facial flushing (both patients) and hypotension (one) occurred during infusion of the contrast agent into the superior mesenteric artery. Because CTAP can demonstrate small hepatic metastases (less than 1 cm in diameter), it is recommended for patients with malignant carcinoid syndrome who are being considered for hepatic resection. The infusion of contrast media through the superior mesenteric artery may induce a carcinoid crisis, and prophylaxis with a somatostatin analogue is suggested. PMID- 8462030 TI - Leaking Baker's cyst detected by magnetic resonance imaging. AB - Popliteal or Baker's cysts, often found incidentally during examination of the knee, are common. The authors report the magnetic resonance imaging (MRI) manifestations of a leaking Baker's cyst that initially presented as thrombophlebitis in a patient who had undergone reconstruction of the anterior cruciate ligament 4 months before; no cyst was present at the time of the surgery. Marked inflammatory changes apparent in the surrounding muscle and subcutaneous tissues were best appreciated in T2-weighted and fat-suppressed inversion recovery images. Although the results of ultrasonography suggested the diagnosis, they were not conclusive; MRI was a useful noninvasive adjunct in making the definitive diagnosis. PMID- 8462031 TI - Anterolateral dislocation of the lumbosacral junction. AB - An unusual case of anterolateral fracture-dislocation of the lumbosacral junction is reported, and seven additional cases from the literature are discussed. The mechanism of injury is forced hyperflexion and shear. The prevalence of neurologic involvement is high, as is the number of fractures of the adjacent spinal elements and the occurrence of disk fragments in the spinal canal. The value of plain radiography and computed tomography in diagnosis and planning treatment is illustrated. PMID- 8462032 TI - Venous thrombosis of the middle lobe after upper lobectomy. AB - The author reports a case of venous thrombosis of the middle lobe occurring after upper lobectomy. Rapid lobar opacification without loss of volume is characteristic of this uncommon postoperative complication. Correct interpretation of the postoperative radiographs and early reoperation are essential. PMID- 8462033 TI - Atypical sperm granuloma of the epididymis mimicking a testicular mass. AB - Ultrasonography (US) plays a crucial role in the evaluation of scrotal masses and is highly accurate in distinguishing extratesticular from intratesticular lesions. Occasionally, however, it may be difficult to distinguish an extratesticular process adherent to the testis from an intratesticular mass on the basis of US findings. The authors present one such unusual case, in which an epididymal sperm granuloma mimicked a testicular mass. PMID- 8462034 TI - Residents' Corner. Answer to case of the month #18. Cervical spinal meningioma. PMID- 8462035 TI - The Canadian radiologist and informed consent. PMID- 8462036 TI - The trachea: normal anatomic features, imaging and causes of displacement. AB - Radiologists have long regarded the trachea as one of their "blind spots," even though this structure can be visualized as well as, if not better than, any other intrathoracic component because of the excellent intrinsic contrast provided by air within the trachea and by the tracheal interfaces with the mediastinum and the lung. Despite this ease of visualization, radiologists may overlook tracheal abnormalities in their diligence in examining the pulmonary parenchyma and the heart. The trachea can be imaged by a variety of techniques, including plain radiography, computed tomography (CT) and magnetic resonance imaging. Important tracheal interfaces include the right and left paratracheal stripes and the tracheoesophageal stripe. The right posterolateral tracheal band is best seen with CT. The trachea is generally a midline structure displaced slightly to the right by the aortic arch. Various conditions, including mediastinal masses and vascular anomalies, may bow, displace or indent the trachea. Such appearances are most commonly seen in patients with thyroid masses or a right-sided aortic arch. Enlarged nodes do not usually narrow the trachea unless they are much harder than the cartilaginous rings, as occurs in nodular sclerosing Hodgkin's disease, or the rings are soft, as is the case in children. PMID- 8462037 TI - Consent: radiologists' dilemma about contrast media. AB - In February 1990 the Conseil d'evaluation des technologies de la sante du Quebec released a report advocating the use of high-osmolar contrast media for "low risk" patients. The authors of the report justified not mentioning to these patients, in the course of obtaining informed consent for examinations requiring intravascular contrast media, that there are two classes of contrast agent. Furthermore, they advocated concealing this policy from the public. In contrast, the authors of this article suggest that informed consent is the product of a dialogue between the consenting person (the patient) and the one requesting consent (the radiologist). Such a dialogue can exist only if the doctor gives the patient sufficient information so that the two are at the same level of understanding; the patient can then make an informed decision. These discussions are held in the name of equity. Three criteria that can be used to test for ethical equity--impartiality, reciprocity and "examplarity"--are discussed. The authors of this paper argue that a policy limiting access to low-osmolar contrast media is justifiable. However, concealing from the patient and the public the existence of a choice of contrast media is considered ethically indefensible. PMID- 8462038 TI - Nonrenal cystic masses in neonates and children. AB - With the increasing use of ultrasonography (US) in children, abdominal cystic masses, many of them nonrenal, are being detected more frequently both before and after birth. Between 1986 and 1991, 20 predominantly cystic abdominal or pelvic masses of nonrenal origin were detected by US in patients less than 10 years of age. Ten of the 20 patients were neonates; in 5 of these the masses were detected antenatally. Pathological correlation was obtained for 16 of the patients. Six of the cysts were ovarian; two represented cystic teratoma, two exhibited torsion and hemorrhage, one was a giant simple cyst and one was a simple cyst with herniation. Six of the lesions were duplication cysts; two were found in the antral region, of which one was ulcerated and had perforated. In the remaining group of eight cysts, three were found in newborns; one represented colonic atresia and another was a choledochal cyst. Several of these nonrenal cystic masses were detected incidentally or in patients with nonspecific abdominal pain. US correctly predicted the location of the cyst and the diagnosis in most patients. In many of the patients the masses were complicated by other problems that required diagnosis and treatment. PMID- 8462040 TI - About that fee increase... PMID- 8462039 TI - Intravenous administration of gadolinium in the evaluation of rheumatoid arthritis of the shoulder. AB - The authors sought to determine the utility of intravenously administered gadolinium chelates in magnetic resonance imaging (MRI) of patients with rheumatoid arthritis of the shoulder. One shoulder was examined for each of 12 patients--6 men and 6 women, ranging in age from 48 to 71 (average 63) years- with well-established disease. The patients had had the disease for 1 to 25 (average 13) years. Static MRI was performed before and after infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) (0.1 mmol/kg body weight); T1-weighted or proton-density images (repetition time [TR] 600 to 1000 ms, echo time [TE] 15 to 30 ms) were obtained. Images obtained after enhancement were particularly useful in the differentiation of pannus from fluid and also allowed improved delineation of tears of the supraspinatus tendon. In addition, contrast-enhanced dynamic gradient-echo spoiled GRASS sequences (TR 50 ms, TE 11 ms, flip angle 70 degrees) were obtained for all patients; for these sequences the same slice was imaged repeatedly at 20-second intervals. The rate of increase of signal intensity in abnormal synovium varied from 0.64 to 5.83 (average 2.30, standard deviation [SD] 1.67) units/second; the enhancement factor ranged from 1.55 to 4.64 (average 2.63, SD 0.98). The authors conclude that for imaging the shoulder enhancement with Gd-DTPA allows improved distinction between synovial thickening and joint effusion and may improve assessment of the rotator cuff. The wide range in the rate of signal increase and total enhancement during dynamic imaging probably reflected heterogeneity in the study population. PMID- 8462041 TI - Toronto clinic's new approach. PMID- 8462042 TI - Toronto clinic's new approach. PMID- 8462043 TI - Toronto clinic's new approach. PMID- 8462044 TI - Toronto clinic's new approach. PMID- 8462045 TI - Physicians and abortion. PMID- 8462046 TI - Physicians and abortion. PMID- 8462047 TI - Nasogastric tube placement. PMID- 8462048 TI - Four decades of glucocorticosteroid immunosuppression. PMID- 8462049 TI - Coordination of guidelines development. PMID- 8462050 TI - Canadian physicians and euthanasia: 1. An approach to the issues. PMID- 8462051 TI - Do physicians locate as spatial competition models predict? Evidence from Alberta. AB - This article analyses how physicians choose locations of practice in response to spatial competition forces and considers the implications of such choices for public policy to alleviate shortages of practitioners in rural areas. The predicted geographic distribution of physicians, as determined through spatial competition modelling, was compared with the actual distribution of physicians in 1990 among Alberta's 19 census divisions. Physicians were found to respond to spatial competition forces in choosing where to practise, with the qualification that 1 urban patient had a demand weight equal to 2.32 rural patients. A policy to attract more physicians to rural areas by means of income subsidies is technically feasible but expensive. The high cost means that alternative policies such as a bigger and more effective ambulance network to transport patients to medical centres should become the focus of public policies to improve health care in rural areas. PMID- 8462052 TI - Learning the secrets of human chromosomes: Canada's role in an international project. PMID- 8462053 TI - Cesarean section: analysis of the experience before and after the National Consensus Conference on Aspects of Cesarean Birth. AB - OBJECTIVE: To examine the effect of recommendations to reduce the cesarean section rate issued by the National Consensus Conference on Aspects of Cesarean Birth in 1986 on obstetric practices and to identify current patient factors that predict cesarean section. DESIGN: Descriptive retrospective cross-sectional study. SETTING: A tertiary care perinatal referral centre and a general teaching hospital with a level 2 nursery in Hamilton, Ont. PATIENTS: All patients who gave birth at the two hospitals in 1982 (4121 women) and 1990 (4431). MAIN OUTCOME MEASURES: Cesarean section rates and indications and predictors of cesarean section. RESULTS: Although a trial of vaginal delivery after cesarean section was offered 93% more often in 1990 than in 1982 (p = 0.0002), the rate of vaginal delivery increased only 2.6%, for a reduction of 8.7% in the total cesarean section rate and of 15% in the repeat cesarean section rate. The incidence rate and treatment of dystocia did not change. The rate of cesarean section for breech presentation remained unchanged, and fetal distress was rarely confirmed with pH measurement in scalp blood before cesarean section. The most important predictors of cesarean section in 1990 were previous cesarean section and labour induction. For the nulliparous women and the multiparous women with no previous cesarean section labour induction was the most important predictor. CONCLUSIONS: The rate at which patients with previous cesarean section are offered a trial of vaginal delivery has increased significantly since 1982; however, the total and repeat cesarean section rates have not decreased proportionally. Induction of labour is currently the most important correctable predictor of cesarean section. The active management of dystocia, efforts to increase the rate of vaginal breech delivery and appropriate methods to diagnose fetal distress need to be improved; such improvements should reduce the cesarean section rate further. PMID- 8462054 TI - Contamination of human ovarian follicular fluid and serum by chlorinated organic compounds in three Canadian cities. AB - OBJECTIVES: To determine the extent of contamination of ovarian follicular fluid and serum samples in women undergoing in-vitro fertilization and to study the effect of the contaminants on reproductive outcome. DESIGN: Inception cohort study. PATIENTS: Seventy-four women undergoing in-vitro fertilization at three regional clinics in Halifax, Hamilton, Ont., and Vancouver. MAIN OUTCOME MEASURES: Follicular fluid and serum levels of contaminants, cleavage rates and time to cleavage of first egg. RESULTS: Five chlorinated organic chemicals were frequently found in the two types of samples: alpha-chlordane (ALCH), dichlorochlorophenylethylene (DDE), heptachloroepoxide-oxychlordane (OXCH), hexachlorobenzene (HCB) and polychlorinated biphenyl (PCB). The levels were generally low. Regional differences between the three clinics were present. Samples from the Halifax clinic had the lowest frequency and level of contamination. The source of drinking water (well, bottled or municipal) was an important confounder. The concentrations of the five contaminants did not affect the cleavage rate or the time to cleavage of the first egg. CONCLUSION: Trace amounts of toxic and persistent chlorinated organic chemicals found in the follicular fluid of Canadian women undergoing in-vitro fertilization did not seem to have any adverse biologic effect on the rate of fertilization and the time to cleavage. Reasons for regional differences in the concentrations of contaminants require further study. PMID- 8462055 TI - Advance directives: the views of health care professionals. AB - OBJECTIVES: This study examined the views and experiences of 20 physicians and 20 nurses at a major Canadian teaching hospital regarding the use of advance directives in clinical care. DESIGN: The participants were purposively drawn from four clinical specialties: family and community medicine, oncology, intensive care and geriatrics. Detailed interviews were conducted in person. Content analysis was used to code the data, which were further analysed with both quantitative and qualitative techniques. MAIN RESULTS: Thirty-nine of the 40 participants favoured the use of advance directives in clinical care; physicians had somewhat less positive attitudes than nurses toward such directives. Advance directives were thought by participants to be helpful in resolving disagreements between patients and their families about treatment options; in making patients more comfortable, both physically and psychologically, during the process of dying; and in opening up communication and trust among patients, their families and health care professionals. Concerns about the use of advance directives focused on the lack of clarity in some patients' instructions, the absence of legal status for directives, the possible interference with a practitioner's clinical judgement, the adequacy and appropriateness of patients' information about their circumstances, and the type of intervention (passive or active) requested by patients. CONCLUSIONS: New regulations and legislation are making the use of advance directives more widespread. Health care professionals should participate in the development and implementation of these directives. Continuing professional education is essential in this regard. PMID- 8462056 TI - The insulin resistance-dyslipidemia syndrome: the most prevalent cause of coronary artery disease? PMID- 8462057 TI - Ottawa announces hike in funding for AIDS research, education. PMID- 8462058 TI - Researchers, animal rights activists fight public relations war at Western. PMID- 8462059 TI - Society must lead in determining Canadian position on euthanasia, doctors say. PMID- 8462060 TI - In the US, AIDS has become a "marginal" disease that affects thousands. PMID- 8462061 TI - Calgary hospital's cooperative care program: "the care went from good to excellent". PMID- 8462062 TI - Testing program an attempt to help managers cope with growing stress in civil service. PMID- 8462063 TI - Seek funding from provinces or private sector, not Ottawa, researchers told. PMID- 8462064 TI - London's Gordon Museum provides insight into some remarkable medical history. PMID- 8462065 TI - Comparative morphology of sulfur mustard effects in the hairless guinea pig and a human skin equivalent. AB - A commercially available human skin equivalent (HSE) was used as an in vitro organotypic skin model to study temporal morphological effects of sulfur mustard gas (HD). Light and electron microscopic analyses of the HD-human skin equivalent model (HD-HSE) were compared to the HD-hairless guinea pig model (HD-HGP). HSE samples were exposed to 10 microliters HD vapor for 8 min and harvested at selected times up to 24 h. Skin sites of HGP were exposed to the same vapor dose or to 2.0 microliters liquid HD for 30 min and collected at 12 and 24 h. In both models, basal cells of the stratum germinativum were selectively affected. The HD HSE study revealed that basal cell changes began 3 to 6 h following exposure. These early cellular changes included an acantholysis of some basal cells with widening of intercellular spaces, disruption of desmosomal attachments, nuclear pyknosis, perinuclear blebbing and repositioning of cytoplasmic tonofilaments to a perinuclear position. At 12 to 24 h, basal cell pathology progressed to diffuse swelling of endoplasmic reticula, cytoplasmic vacuolations and necrosis which now extended to supra basal cell layers. Comparing basement membrane zone effects, HD HGP consistently developed characteristic microblisters at the dermal-epidermal junction; however, HD-HSE with its absence of a morphologically distinguishable basement membrane did not. Instead, cellular fragments, granules and debris accumulated early in this area to thicken regions usually assigned to the lamina lucida and lamina densa of a true basement membrane leading to complete separation of dermis from epidermis at later time periods. PMID- 8462066 TI - Ultrastructural and morphometric changes in somatotropic cells following intraventricular administration of Met-enkephalin to rats. AB - An ultrastructural and morphometric study of Kurosumi et al. (1986) on type 1 GH cells in adult Sprague-Dawley rats, after the intraventricular administration of Met-enkephalin, with or without prior intraperitoneal administration of naloxone, was carried out and then compared to the same cellular type of untreated animals and of animals intraventricularly treated with distilled water, used as controls. The study demonstrated an increase of cellular (p < 0.05) and nuclear (p < 0.05) areas, an enlargement and dilation of the cisternae of the Golgi complex, with an increase in the Golgi area (p < 0.01) and the immature granules (p < 0.01); a greater development of the rough endoplasmic reticulum and an increase in the number of exocytosis (p < 0.01) and, only in male rats, an increase in the mature secretory granules (p < 0.01). The prior administration of naloxone prevented the appearance of these changes and also produced an increase (p < 0.01) of the organelles involved in the crinophagic phenomenon. These results suggest that the opioids play a modulating role, stimulating the synthesis and secretion of GH, which affects the ultrastructural features of the hypophyseal GH cells. PMID- 8462067 TI - Chronic lead exposure induces ultrastructural alterations in the monkey seminal vesicle. AB - Lead is a toxic and carcinogenic metal that has been extensively associated with male reproductive abnormalities. The purpose of this study was to establish the effects of lead on the primate seminal vesicle. Sixteen cynomolgus monkeys maintained in environmentally controlled conditions were orally administered gelatin capsules containing 1500 micrograms lead acetate/kg bw/day. Monkeys were randomly assigned to the following groups: control (n = 3) which received 95% glycerol and 5% distilled water (vehicle) over their lifetime, infancy (limited to the first 400 days of life; n = 4), post-infancy (dosed following 300 days of life to 9 years of age; n = 5) and lifetime exposure (9 years; n = 4). At necropsy, the seminal vesicles from each animal were removed, fixed in glutaraldehyde, and processed for ultrastructural analysis by conventional methods. The glands from animals in the control group consisted of acini lined by two cell types, viz., tall columnar secretory cells, and round basal cells. Secretory cells possessed microvilli, basally located nuclei surrounded by much rough endoplasmic reticulum, a few lipid droplets, and supra-nuclear regions dominated by pleomorphic membrane-limited secretory granules. All the treated groups exhibited an augmentation in the number of lipid droplets within the secretory cells. In both the infancy and post-infancy groups, a marked reduction in electron-dense cores of the secretory droplets was observed in severely affected regions of the glands. These findings support the evidence that lead is a potent reproductive toxicant, however, further research is needed to determine the consequences of this damage on reproductive performance. PMID- 8462068 TI - Studies on varicocele. II. The inhibin secretion. AB - In this paper a previous interpretation given by the authors concerning one of the ways varicocele can affect fertility is confirmed. Moreover, it is definitely demonstrated that the high temperature stimulates inhibin secretion (and probably the testosterone-estradiol conversion) in the Sertoli cells, while the somatomedin secretion in vitro seems to be unaffected. It means that the action of the temperature on the germinal cells seems to be mediated by the pathway: inhibin (plus estradiol)-->pituitary-->FSH. Inhibin in the Golgi complex of Sertoli and germinal cells has been detected by electron microscopical immunocytochemical techniques. PMID- 8462069 TI - The role of RCA-binding sites in the adhesion of trypanosoma cruzi to heart muscle cells, as revealed by electron spectroscopic imaging. AB - The involvement of host-cell surface membrane components during T. cruzi-heart muscle cell (HMC) interaction was investigated. We used the lectin RCA I (Ricinus communis), which binds to residues of D-galactose, conjugated with ferritin as a tool to reveal the role played by lectin-binding sites during adhesion of T. cruzi to HMC. With electron spectroscopic imaging (ESI) it was possible to observe a concentration of RCA I-ferritin particles on the surface membrane of HMC at the site of parasite attachment. This suggested that migration of galactosyl residues was occurring during the cellular recognition process, particularly since these particles were absent in the immediate vicinity of the attachment site, while being present in other regions of HMC membrane not related to the attachment sites. No region of the parasite's cell body was observed to have preferential status for the purposes of adhesion to HMC. PMID- 8462070 TI - Tracheal epithelium of bonnet monkey (Macaca radiaca) and its response to ambient levels of ozone. A cytochemical study. AB - The effect of 6 or 90 days exposure to 0.15 or 0.30 ppm of ozone on the morphology or carbohydrate cytochemistry of bonnet monkey tracheal epithelium was studied. Ozone treatment induced damages and necrotic phenomena of ciliated cells, as well as a significant increase in the population density of small mucous granule (SMG) cells compared to controls. In addition, the appearance of 'intermediate' cells, a type of nonciliated cells which was not observed in controls, was noticed. Characterization of the secretory cell carbohydrates with the PA-TCH-SP, HID-TCH-SP and LID-TCH-SP sequences indicated the existence of periodate-reactive sulfated and carboxylated polysaccharides in both treated and control monkeys. The luminal surface of the affected tracheal cells, however, exhibited a glycocalyx more rich in mucosubstances than the control animals. The possible role of 'intermediate' and SMG cells in repairing the injured epithelial regions, as well as the significance of the ozone concentrations used in relation to the ozone range measured in photochemical smog are discussed. PMID- 8462071 TI - Immunocytochemical localization of surface and intracellular antigens recognized by human sera in microfilariae of Wuchereria bancrofti. AB - Sera from patients with various clinical pictures of lymphatic filariasis, including tropical pulmonary eosinophilia (TPE), were used for the localization of surface and intracellular antigens in microfilariae of Wuchereria bancrofti embedded in Lowicryl K4M. Very few or no antigenic sites were located on the outer face of the sheath. The most inner layer, as well as the space between the cuticle and the sheath, was intensely labeled. Sera from TPE patients intensely labeled the cuticle and the cytoplasm of muscle cells. PMID- 8462072 TI - Ultrastructural evidences of a distinct axial domain within native rat tail tendon collagen fibrils. AB - The structure of collagen fibrils of tail tendon in young and mature rats was investigated by transmission (TEM) electron microscopy after cytochemical methods associated with special procedures of dehydration and fixation. All the collagen fibrils show a central condensed material of 4 nm in diameter which remains preserved even when fibrils have been swollen and partly disorganized by the ethyl glycol dehydration. A cytochemical characterization using PTA and TCH treatments strongly suggests the glycoprotein nature of this central compact material and reveals the heterogeneous structure of each fibril. The first morphological evidence that the construction of the collagen fibrils must take place around a condensed material which serves as a scaffolding is obtained. These observations are in agreement with the now well established existence of heterotypic collagen fibrils in many extracellular matrices. PMID- 8462073 TI - Infiltration of hypertrophic esophageal smooth muscle by mast cells and basophils. AB - Partial obstruction leads to chronic distension and muscular hypertrophy of the opossum esophagus. The smooth muscle cells of the circular muscle layer enlarge, become pleomorphic and are surrounded by an amorphous ground substance in the extracellular space. Here we describe the histological and ultrastructural features of a peculiar cellular infiltrate in the hypertrophic smooth muscle. The infiltrate consisted uniquely of mast cells and basophils. In per unit area, the number of mast cells increased from 0.9 +/- 0.1 cells in controls to 3.7 +/- 0.2 in hypertrophic smooth muscle; the corresponding numbers for basophils were 2.5 +/- 0.2 and 7.2 +/- 0.3 cells. Cells were seen primarily in the septal spaces of the circular muscle layer and at the interface of the circular and longitudinal muscle layer. The cytoplasm of basophils is normally packed with round and oval granules. The granules stain metachromatically and with varying intensity on Wright-Giemsa stains. On transmission electronmicroscopy, granules display a membrane and a great diversity in the structure of their luminal contents. In hypertrophic muscle, most granules were discharging their contents into the cytoplasm or extracellular space. The membranes of adjacent empty granules then fused to form a chain of vacuoles. Similar changes occurred also in the mast cells which differed from the basophil by their lack of nuclear lobulation and by the greater homogeneity of their cytoplasmic granules. It is possible that these inflammatory cells are involved in the reconstruction of the smooth muscle and its connective tissue which occur during esophageal distension and hypertrophy. PMID- 8462074 TI - Successful excimer laser angioplasty following unsuccessful primary balloon angioplasty. AB - We report five patients where excimer laser coronary angioplasty facilitated successful balloon dilatation of heavily calcified lesions that could not be dilated by conventional angioplasty techniques alone. In each case, the lesion was crossed successfully with a guide wire. Conventional angioplasty failed because of inability to cross the lesion with a balloon (four lesions) or inability to dilate the lesion with balloon inflation (two lesions). These cases illustrate an indication for excimer laser coronary angioplasty as an adjunctive procedure in heavily calcified coronary stenoses. PMID- 8462075 TI - Is aggressive heparinization necessary for elective PTCA? AB - The optimal level of heparin anticoagulation for elective PTCA is unknown. To determine if PTCA complications are related to the level of anticoagulation, serial ACT values were prospectively measured in 189 patients undergoing 201 elective PTCA procedures. The mean heparin dose before balloon inflation (pre inflation) was 10,100 units, and the mean dose per procedure was 13,200 units. The mean pre-inflation ACT was 295 sec, but was < 300 sec in more than 50% of patients. Acute complications were not related to any ACT parameter and the development of new intracoronary thrombus was not observed. In elective PTCA procedures, the routine monitoring of ACT values is unnecessary when standard heparin doses are used. PMID- 8462076 TI - Digital geometric measurements in comparison to cinefilm analysis of coronary artery dimensions. AB - Six months follow-up post-PTCA angiograms from 31 patients were acquired digitally and on cinefilm and used for a comparison of geometric coronary measurements at the site of the previous dilatation. On 70 images of 34 coronary segments quantitative analysis was performed both on-line, using the Automated Coronary Analysis package of the Philips Digital Cardiac Imaging System (DCI, pixel matrix 512 x 512) and off-line, using the Cardiovascular Angiography Analysis System (CAAS). With the CAAS a cine-video conversion is performed and a 6.9 x 6.9 mm region of interest from the 18 x 24 mm cineframe is digitized into a 512 x 512 pixel matrix. In both systems the vascular contours are assessed by means of operator-independent edge detection algorithms. The angiographic catheter was used for calibration. Best agreement between DCI and CAAS was found for obstruction diameter and minimal luminal diameter, respectively (r = 0.82; y = 0.12 + 0.97x; SEE = 0.29). The reconstructed reference diameter related to a computed reference contour yields lower correlation (r = 0.76; y = 0.27 + 0.91x; SEE = 0.37). Worst results were obtained from the relative measure of percent diameter stenosis as well as from the derived parameter of plaque area. The on line digital approach of geometric coronary assessments provides good agreement with cinefilm analysis when direct measurements of coronary dimensions are applied. PMID- 8462077 TI - Superior accuracy of anatomic positioning with echocardiographic- over fluoroscopic-guided endomyocardial biopsy. AB - To assess the superior anatomic positioning of echocardiographic-guided endomyocardial biopsy compared to traditional fluoroscopic-guided technique, these two modalities were compared in a blinded fashion during femoral sheath endomyocardial biopsy in 21 patients, 19 being evaluated after orthotopic cardiac transplantation. The simultaneous fluoroscopic and echocardiographic imaging indicated that traditional fluoroscopic positioning of the bioptome against the septum is inaccurate in over half of patients undergoing biopsy. This finding should be considered in cardiomyopathy patients or those at high risk for biopsy related complications. PMID- 8462078 TI - Quantitative evaluation of left ventricular shape in anterior aneurysm. AB - The purpose of the study was to analyze left ventricular (LV) shape in post infarction anterior aneurysm by utilizing quantitative analysis of wall curvature. Forty-one patients (39 men, 2 women; mean age 56 years) subjected to surgical intervention for LV aneurysm complicating an anterior myocardial infarct were retrospectively evaluated. In all patients the presence of resectable aneurysmal tissue had been confirmed by direct surgical examination. Patients with inferior myocardial infarction and patients who had undergone percutaneous transluminal coronary angioplasty (PTCA) or bypass surgery were excluded. Pre intervention ventriculograms (RAO projection) were analyzed. LV wall excluded. Pre-intervention ventriculograms (RAO projection) were analyzed. LV wall motion was studied by applying the centerline method. Regional curvature of end diastolic and end-systolic outlines was calculated at 90 equidistant points from aortic corner (point 1) to mitral plane (point 90). Patients with LV anterior aneurysm show a typical pattern of alterations in wall curvature, which is characterized by a shifting of the angiographic apex (the point with the greatest curvature) towards the mitral plane, and by a sharp shift of curvature values at the antero-basal and infero-apical regions, marking the borders of the sac. These hinge points closely correspond to the external limits of wall motion abnormalities. Significant correlations were found between degree of regional curvature alterations and severity of global LV dysfunction, as indicated by decrease of ejection fraction and increase of end-systolic volume. In conclusion, quantitative evaluation of LV shape by means of wall curvature analysis allows recognition of the characteristic morphologic changes of the aneurysm, i.e., wall expansion and deformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462079 TI - A prospective, randomized, and double-blind trial on the effect of fish oil on the incidence of restenosis following PTCA. AB - Restenosis after successful coronary angioplasty (PTCA) occurs in 25-35% of all procedures. To date, most pharmacologic strategies have failed to reduce the restenosis rate significantly. However, recent studies have suggested a potential benefit of dietary supplementation with omega-3 fatty acids (fish oil) on restenosis following PTCA. The benefit of omega-3 polyunsaturated fatty acids on the incidence of coronary artery restenosis following elective PTCA was assessed in 212 consecutive patients (41 female, 171 male). Following a successful angioplasty, 204 patients received a dietary supplementation with either nine capsules containing fish oil (3.15 g omega-3 fatty acids) or nine placebo capsules containing olive oil. Treatment was started immediately after PTCA and maintained over 4 mon. Compliance was assessed by analysis of lipid fatty acids prior to angioplasty and at 4 mon follow-up. The angiographically determined incidence of restenosis (stenosis diameter > 50%) was 31.2% per lesion in patients receiving fish oil and 33.7% in patients receiving olive oil. Gross progression of coronary artery disease in vessels not subjected to angioplasty was 17% and 16%, respectively. In conclusion, low dose fish oil supplementation begun on the day of a successful coronary angioplasty failed to demonstrate any effect on coronary artery restenosis. PMID- 8462080 TI - Intracoronary blood flow velocity and transstenotic pressure gradient using sensor-tip pressure and Doppler guidewires: a new technology for the assessment of stenosis severity in the catheterization laboratory. AB - In a patient undergoing percutaneous balloon angioplasty of a stenotic proximal right coronary artery the transstenotic pressure gradient was measured using a 0.018" guidewire with a distal optical microsensor. Blood flow velocity was measured proximal to the stenosis using a 0.018" Doppler guidewire. Transstenotic pressure gradient and blood flow velocity were measured in baseline conditions and after intracoronary injection of 12.5 mg of papaverine. Coronary blood flow was calculated from the measured blood flow velocity and the corresponding cross sectional area. The measured pressure gradients were compared with the values derived from the stenosis geometry assessed with quantitative coronary angiography (automated edge detection measurements in two orthogonal views, assuming an elliptical cross-sectional area). The measured transstenotic pressure gradient was 15 mm Hg in baseline conditions and 42 mm Hg at the peak effect of the papaverine injection. A 50% flow velocity increase was observed at peak hyperemia (time-averaged maximal flow velocity = 30 cm/s before and 45 cm/s after papaverine). The transstenotic pressure gradient calculated from the measured stenosis geometry was 20 mm Hg and 42 mm Hg in baseline and hyperemic conditions, respectively. The combined use of a pressure and a Doppler guidewire provides a complete assessment of the transstenotic pressure/coronary flow velocity relation at rest and after pharmacologically induced hyperemia and allows the characterization of stenosis hemodynamics and functional severity. PMID- 8462081 TI - The use of transesophageal echocardiography to avoid left atrial thrombus during percutaneous mitral valvuloplasty. AB - During mitral balloon valvuloplasty, transesophageal echocardiography (TEE) has been employed for the accurate placement of the transseptal needle, guide wires, and balloon catheters and to provide an immediate evaluation of the results of the procedure. We describe a case demonstrating that TEE can be used to avoid a left atrial appendage thrombus during the placement of wires and catheters. With TEE guidance, we feel left atrial appendage thrombi are no longer an absolute contraindication to percutaneous mitral valvuloplasty. PMID- 8462082 TI - Epicardial and subselective transcoronary chemical ablation of incessant ventricular tachycardia. AB - Incessant ventricular tachycardia in patients with severely depressed ventricular function remains a major therapeutic challenge. Although alcohol ablation via the tachycardia related vessel has been shown to be an effective alternative, it might not be applicable in some cases due to anatomic limitations. In three patients with ischemic cardiomyopathy and incessant ventricular tachycardia no effective antiarrhythmic therapy could be found. Alcohol ablation was then attempted but the tachycardia related vessel could not be intubated. A subselective injection of alcohol into a more proximal segment of the coronary artery was then performed in two cases. In one patient as subselective injection was also not possible, the injection was performed epicardially after thoracotomy. Ablation was successful in all cases. In very selected cases of incessant ventricular tachycardia that have failed all other therapeutic interventions, alcohol ablation of the tachycardia can be performed using an epicardial or subselective transcoronary injection of alcohol. PMID- 8462083 TI - Characterization of a saphenous vein graft aneurysm by intravascular ultrasound and computerized three-dimensional reconstruction. AB - Aneurysmal dilatations in saphenous vein grafts are rare complications of coronary artery bypass surgery that mostly represent thin-wall pseudoaneurysms at anastomotic sites. We describe a case of an enlarging distal saphenous vein graft aneurysm in which intravascular ultrasound (IVUS) and computerized three dimensional reconstruction (3DR) of the IVUS images was performed to conclusively demonstrate true aneurysm morphology. Although both atherosclerotic and nonatherosclerotic mechanisms for vein graft aneurysm formation have been previously suggested, IVUS images and 3DR of the aneurysm in this case did not reveal any of the features typical for atherosclerotic lesions. Further, the IVUS images and 3DR suggest that progressive atherosclerosis is not the likely cause of aneurysm formation in this case. This application of IVUS and 3DR provides detailed information about saphenous vein graft aneurysm structure, clues to aneurysm formation, and suggests a natural history that may differ from that of pseudoaneurysms. PMID- 8462084 TI - Percutaneous retrieval of a deformed guidewire by a modified snaring technique. AB - An attempt to percutaneously remove a guidewire from the inferior vena cava was hampered by kinks developing in the wire during snaring. A modified technique was adopted that permitted its retrieval, obviating the need for a formal venotomy. PMID- 8462085 TI - Percutaneous embolization of an arteriovenous fistula of the internal mammary pedicle following sternal wire insertion. AB - A case of traumatic arteriovenous fistula and false aneurysm of the internal mammary artery was encountered following sternal wire insertion during cardiac surgery. The diagnosis was suspected by echo-doppler and confirmed by arteriography allowing percutaneous embolization using cyanoacrylate in the same setting. PMID- 8462086 TI - High flow coronary fistula closure by percutaneous coil packing. AB - Few cases of transcatheter coronary fistula closure have been reported. High flow coronary fistulae are usually treated by surgery. This case report presents a 5.4 liters/min flow coronary fistula percutaneously closed by steel coils. This large flow needed the packing of 25 coils, 10-15 cm long, for its total occlusion. PMID- 8462087 TI - Transcatheter coil occlusion for treatment of left internal mammary-anterior descending artery steal phenomenon. AB - A 60-yr-old female with previous bypass surgery including LIMA-LAD graft presented with unstable angina due to steal phenomenon caused by a large pectoral branch of LIMA. Transcatheter coil occlusion of the pectoral branch was successfully performed. This procedure should be considered in similar cases. PMID- 8462088 TI - Retrieval of a lost coronary stent from the descending aorta using a PTCA balloon and biopsy forceps. AB - We report a case of unsuccessful stenting of a right coronary artery after acute dissection during percutaneous transluminal coronary angioplasty (PTCA). The stent was lost in the descending aorta and we used an original technique to remove it from the arterial bed by using both a very low profile balloon and a 6F bioptome. PMID- 8462089 TI - Rescue transcatheter embolectomy following complicated transluminal extraction atherectomy of a coronary vein graft. AB - Transluminal extraction catheter atherectomy of a saphenous vein graft to the right coronary artery was performed in a 72-year-old female and was complicated by distal embolization. A successful transcatheter aspiration of the embolic plaque was achieved. The usefulness of this technique as a coronary intervention is discussed. PMID- 8462090 TI - Kissing balloon technique in complex PTCA: single guiding catheter and dual wire rapid exchange system. AB - This report is a description, based on four cases, of a variation from previously described approaches for accomplishing the "kissing balloon" technique for complex PTCA. We describe a case in which a single guiding catheter is utilized in combination with two over-the-wire monorail type balloon catheters allowing use of standard length (175 cm) guidewires. Various combinations of balloon diameters are described. We believe this approach has significant advantages over other techniques, principally in its rapid and easy usage. PMID- 8462091 TI - Reference level for pressure measurements. PMID- 8462092 TI - Low profile catheter use. PMID- 8462093 TI - Motor neurons and neurofilaments in sickness and in health. PMID- 8462094 TI - High resolution cosmid and P1 maps spanning the 14 Mb genome of the fission yeast S. pombe. AB - Gridded on high density filters, a P1 genomic library of 17-fold coverage and a cosmid library of 8 genome equivalents, both made from S. pombe strain 972h-, were ordered by hybridizing genetic markers and individual clones from the two libraries. Yeast artificial chromosome (YAC) clones covering the entire genome were used to subdivide the libraries, and hybridization of short oligonucleotides and DNA pools made from randomly selected cosmids provided further mapping information. Restriction digests were generated as an independent confirmation of the clone order. The high resolution clone map was aligned to the genetic map and the physical Notl and YAC maps. The usefulness of the various mapping techniques and cloning procedures could be assessed upon the different data sets. PMID- 8462095 TI - A 13 kb resolution cosmid map of the 14 Mb fission yeast genome by nonrandom sequence-tagged site mapping. AB - We present the application of a nonrandom sequence-tagged site (STS) content detection method in mapping an entire genome, that of fission yeast. The novelty of our strategy is in the use of STS probes made from both ends of cosmid clones, selected on the basis of "sample without replacement" (only library clones that show no previous positive hybridization are selected and made into probes). We developed powerful techniques, based on consistency analysis, for error detection and contig assembly. In addition, we probed our library with genetically mapped markers and Notl or Sfil linking clones, thereby anchoring contigs onto chromosomes. Our map contains more than 1000 sites, including genes (most were previously unmapped), occurrences of known repetitive elements, and Notl-Sfil restriction sites. PMID- 8462096 TI - Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. AB - The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is a component of high and intermediate affinity IL-2 receptors that is required to achieve full ligand binding affinity and internalization. We have localized the IL-2R gamma gene to human chromosome Xq13. Genetic linkage analysis indicates that the IL-2R gamma gene and the locus for X-linked severe combined immunodeficiency (XSCID) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with XSCID has a different mutation in his IL-2R gamma gene resulting in a different premature stop codon and predicted C-terminal truncation. These data establish that XSCID is associated with mutations of the IL-2R gamma gene product. Since XSCID is characterized by absent or markedly reduced numbers of T cells, our findings imply that IL-2R gamma plays a vital role in thymic maturation of T cells. These results also have important implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID. PMID- 8462097 TI - An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. AB - Activation of the sevenless protein-tyrosine kinase is required for the proper specification of R7 photoreceptors in the Drosophila eye. The activation of a Ras protein, p21Ras1, is a crucial early event in the signaling pathway, and constitutive activation of p21Ras1 is sufficient to induce all of the effects of sevenless action. Here we report that another gene, E(sev)2B, required for proper signaling by sevenless encodes a protein of the structure SH3-SH2-SH3. We further provide evidence that the E(sev)2B protein is required for activation of p21Ras1 but not for any subsequent events, and that this protein can bind in vitro to sevenless and to Son of sevenless (Sos), a putative guanine nucleotide exchange factor for p21Ras1. These results suggest that the E(sev)2B protein may act to stimulate the ability of Sos to catalyze p21Ras1 activation by linking sevenless and Sos in a signaling complex. We have renamed the E(sev)2B locus downstream of receptor kinases (drk). PMID- 8462098 TI - A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. AB - A Drosophila gene (drk) encodes a widely expressed protein with a single SH2 domain and two flanking SH3 domains, which is homologous to the Sem-5 protein of C. elegans and mammalian GRB2. Genetic analysis suggests that drk function is essential for signaling by the sevenless receptor tyrosine kinase. Drk biological activity correlates with binding of its SH2 domain to activated receptor tyrosine kinases and concomitant localization of drk to the plasma membrane. In vitro, drk also binds directly to the C-terminal tail of Sos, a Ras guanine nucleotide releasing protein (GNRP), which, like Ras1 and drk, is required for sevenless signaling. These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. The conservation of these signaling proteins during evolution indicates that this is a general mechanism for linking tyrosine kinases to Ras. PMID- 8462099 TI - The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain. AB - The POU-specific (POUs) domain, in association with a POU-type homeodomain, forms the bipartite DNA-binding POU domain. The solution structure of the Oct-1 POUs domain has been determined by multidimensional nuclear magnetic resonance spectroscopy and consists of four alpha helices surrounding a conserved hydrophobic core. The POUs domain is structurally similar to the DNA-binding domains of the bacteriophage lambda and 434 repressors and 434 Cro. These domains exhibit superimposable helix-turn-helix (HTH) motifs, except that in the POUs domain, the first helix and the linker to the second helix of the motif are extended. The conserved structural features have been used to propose a plausible model for DNA binding by the POUs domain. A human dwarfism mutation that affects positive control in the related POU domain protein Pit-1 maps to the same region of the HTH motif as do positive control mutations in lambda repressor. PMID- 8462100 TI - Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. AB - Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accumulate NF-L to approximately 4-fold the normal level in the sciatic nerve. In young animals, the motor neurons of the ventral horn of the spinal cord have massive accumulations of neurofilaments, swollen perikarya, and eccentrically localized nuclei. NF-L accumulation is accompanied by an increased frequency of axonal degeneration, proximal axon swelling, and severe skeletal muscle atrophy. These data indicate that extensive accumulation of neurofilaments in motor neurons can trigger the neurodegenerative process. PMID- 8462101 TI - Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. AB - We generated four transgenic mice with a 34 kb genomic fragment including the complete human neurofilament heavy (NF-H) gene. This human NF-H fragment contained all regulatory elements for tissue-specific expression, and in two transgenic lines, human NF-H proteins were produced at levels up to 2-fold the levels of endogenous mouse NF-H protein. By 3-4 months of age, these NF-H transgenics progressively develop neurological defects and abnormal neurofilamentous swellings that are highly reminiscent of those found in amyotrophic lateral sclerosis (ALS). We propose that a modest up-regulation of NF H cross-linkers can result in an impairment of neurofilament transport, causing neuronal swellings with ensuing axonopathy and muscle atrophy, a mechanism of pathogenesis pertinent to the possible etiology of ALS. PMID- 8462102 TI - In vivo evidence that transcription and splicing are coordinated by a recruiting mechanism. AB - We describe the nuclear organization of pre-mRNA processing components in HeLa cells upon adenovirus 2 infection and their relationship to the localization of viral RNA sequences. We observe a redistribution of cellular splicing factors as well as RNA polymerase II and heterogeneous nuclear ribonucleoprotein particle proteins to sites of viral RNA transcription. Similar results were obtained in cells transiently transfected with a plasmid containing a portion of the beta tropomyosin gene. Our findings demonstrate a very close association between RNA transcripts and transcription and pre-mRNA splicing factors, suggesting that these processes are both temporally and spatially linked in the cell nucleus. Furthermore, these data suggest a recruiting mechanism that regulates the localization of transcription and splicing factors in response to the initiation of active transcription. PMID- 8462103 TI - The IL-2/IL-2 receptor system: a current overview. PMID- 8462104 TI - Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. AB - The mouse insulin-like growth factor type 2 receptor (Igf2r) is imprinted and expressed exclusively from the maternally inherited chromosome. To investigate whether methylation could function as the imprinting signal, we have cloned 130 kb from the Igf2r locus and searched for sequences methylated in a parental specific manner. Two regions have been identified: region 1 contains the start of transcription and is methylated only on the silent paternal chromosome; region 2 is contained in an intron and is methylated only on the expressed maternal chromosome. Methylation of region 1 is acquired after fertilization, in contrast with the methylation of region 2, which is inherited from the female gamete. Methylation of region 2 may mark the maternal Igf2r locus in a manner that could act as an imprinting signal. These data suggest that the expressed locus carries a potential imprinting signal and imply that methylation is necessary for expression of the Igf2r gene. PMID- 8462105 TI - Bacterial sex pheromone-induced plasmid transfer. PMID- 8462106 TI - Identification of a natural killer enhancing factor (NKEF) from human erythroid cells. AB - We have previously shown that RBC significantly augment NK cell-mediated cytotoxicity when added at the initiation of cytotoxicity assays. We now report that RBC cytosol contains a soluble factor that mediates a similar enhancement of NK activity when the factor is precoated on a plastic surface. We have purified this NKEF by ammonium sulfate precipitation, ion exchange chromatography, and gel filtration HPLC. While gel filtration HPLC shows that NKEF has an apparent molecular mass of between 300 and 400 kDa, SDS-PAGE analysis indicates an apparent molecular weight of 48 and 24 kDa under nonreducing and reducing conditions, respectively. Immune serum obtained from a rabbit immunized with purified NKEF blocks NKEF augmentation of NK activity. In contrast, preimmune serum fails to inhibit NKEF activity. Anti-NKEF antibody reacts with the cytosol of NK-sensitive erythroleukemic target cell K562. Western blot analysis indicates that this antibody recognizes a 24-kDa protein both in RBC and in K562. We have generated tryptic peptides from NKEF and obtained partial amino acid sequences from three of the peptides. Two of the sequences show no significant homology with any known sequences. The third sequence shows partial identity with a deduced sequence from a murine erythroleukemia-related gene. Thus, NKEF is a novel protein with unique amino acid sequence. Our results of NKEF in RBC suggest that RBC could play an important role in regulating NK function. PMID- 8462107 TI - The influence of DNA structure on the in vitro stimulation of murine lymphocytes by natural and synthetic polynucleotide antigens. AB - Although DNA is generally considered to be a poor immunogen, recent evidence suggests that DNA from various species differ in their immunological activity and that bacterial DNA can induce the in vitro proliferation of normal murine B cells. To delineate structural features of DNA associated with mitogenic activity, the response of murine lymphocytes to various natural and synthetic polynucleotides was determined. Both ss and dsDNA from two different bacterial strains were equally effective in inducing proliferation. This response was independent of adenosine methylation, since DNA from dam- Escherichia coli stimulated proliferation. Among the synthetic polymers tested, only the duplexes poly(dG).poly(dC), and poly(dG.dC) were mitogenic, while polymers containing dA, dT, or dI alone or in combination with dG and dC were inactive. The mitogenic activity of poly(dG.dC) was eliminated, however, upon substitution of rG for dG or 5medC for dC. The mitogenic activity did not require high molecular weight DNA since active polymers ranged in size from approximately 260 to 800 base pairs. In addition, E. coli DNA fragments of 50-300 and 125-600 bases were mitogenic. Together, these data suggest that the mitogenic activity of DNA is dependent on sequence-specific determinants that can be presented by synthetic DNA duplexes as well as bacterial ss and dsDNA. PMID- 8462108 TI - Negative selection of thymus-dependent CD4+8+ intestinal intraepithelial lymphocytes by internal superantigens. AB - CD4 and CD8 double-positive (DP) T cells were transiently found in the Peyer's patch of mice 2 to 3 weeks after birth and preceded the appearance of DP intestinal intraepithelial lymphocytes (iIEL). DP iIEL were detected in euthymic specific pathogen-free mice, but not in athymic and germ-free mice. The pattern of V beta genes expressed on these DP iIEL was similar to that of CD4 single positive peripheral T cells, which reflected the negative selection by internal superantigens, M1s, and I-E. CD8 SP T cells did not receive such a strict negative selection with these antigens. DP iIEL expressed a high density of T cell receptor alpha beta and CD3 and responded to immobilized anti-CD3 to undergo blastogenesis and de novo IL2 receptor expression. These results indicate that DP iIEL are mature thymus-dependent T cells immigrated to intraepithelial space via the Peyer's patch in response to intestinal antigenic stimulation. PMID- 8462109 TI - Characterization of lymphokine-activated killing by human peripheral blood mononuclear cells stimulated with interleukin 2 (IL-2) analogs specific for the intermediate affinity IL-2 receptor. AB - Interleukin 2-stimulated human peripheral blood mononuclear cells (PBMC) generate lymphokine-activated killing (LAK). Using the IL-2 analogs R38A and F42K, which interact primarily with the beta and gamma subunits of the IL-2 receptor, we assessed the roles of IL-2R beta gamma and the high-affinity IL-2 receptor complex in LAK activation. Although the kinetics of LAK activation were identical, lytic activity was approximately 30% lower and proliferation was up to 55% lower in those PBMC stimulated by R38A or F42K than in those exposed to wild type IL-2. The percentage of cells expressing cell-surface markers such as CD3, CD4, CD8, and CD16 was not significantly different after treatment with wild-type IL-2, R38A, or F42K; however, the proportion of cells expressing IL-2R alpha increased dramatically in response to stimulation by F42K (30%) compared to stimulation by either rIL-2 or R38A (15%). In addition, by Day 7 the concentration of soluble IL-2R alpha in analog-stimulated LAK culture supernatants was 50-75% less than that from wild-type IL-2-cultured cells. These findings suggest that interaction of IL-2 with IL-2R beta gamma alone is sufficient for both proliferation and the generation of LAK, and that stimulation with subunit-specific IL-2 analogs results in differential regulation of the IL 2R alpha on human LAK cells. PMID- 8462110 TI - Protection against apoptosis in chicken bursa cells by phorbol ester in vitro. AB - Like the thymus, the bursa of Fabricius is a site of massive lymphopoiesis accompanied by cell death in vivo. In the present study we have, therefore, examined whether chicken bursa and thymus cells exhibit apoptosis. Bursa and thymus cells from SC chickens, 4-10 weeks of age, were incubated for 8-24 hr with various reagents. Genomic DNA was isolated, electrophoresed in 3% Nusieve agarose gels, and examined for patterns of DNA fragmentation. A laddering of DNA in multiples of 200 base pairs, indicative of apoptosis, was observed particularly with bursa and, to a much smaller extent, with thymus or spleen cells. These patterns of DNA fragmentation from bursa cells could be prevented by adding phorbol myristate acetate (PMA) but not by its inactive analogue 4 alpha-PMA during culture. Ionomycin is not required for this effect and, alone, appears to be slightly toxic for bursa cells, although it does not inhibit the effect of PMA. PMA did not affect the degree of DNA fragmentation in spleen or thymus cells. The addition of the protein kinase C (PKC) inhibitor staurosporine abolished both the preventive effect of PMA on apoptosis and its protective effect on bursa cells, as assayed by [3H]thymidine incorporation 24-48 hr after the initiation of cultures. PKC inhibitors also prevented the proliferation inducing effect of PMA + ionomycin on spleen cells. It is concluded that the activation of protein kinase C and perhaps other kinases protects against apoptosis in cultured bursa cells. PMID- 8462111 TI - Detachment and lysis of adherent target cells by CD4+ T cell clones involve multiple effector mechanisms. AB - Detachment of adherent targets from their substratum is a unique activity of both CD8+ and CD4+ T cells. Recently, we have demonstrated that with mixed, alloreactive populations, CD4+ T-cell-mediated detachment is kinetically distinct from lysis and requires protein synthesis. Heterogeneity of effector phenotypes precluded further elucidation of the mechanism of detachment at the mixed population level. Here, we examine further the mechanism of target cell detachment by CD4+ cells using clones which differ in lytic efficiency and demonstrate that detachment of adherent targets from their substratum (1) may result from either protein synthesis-dependent or independent pathways, which can be correlated with differences in clonal lytic phenotype, (2) is contact dependent and does not involve soluble factors, (3) can be pharmacologically uncoupled from IL4 production, as a measure of cytokine release, and (4) fails to correlate with perforin expression by immunocytochemistry. Finally, isolated granule preparations are unable to mediate detachment independent from lysis. PMID- 8462112 TI - Immunization with recombinant Escherichia coli expressing retinal S-antigen induced experimental autoimmune uveitis (EAU) in Lewis rats. AB - Previously we have reported that microbial proteins having sequence homology with uveito-pathogenic peptide (peptide M) of retinal S-antigen (S-Ag) induced experimental autoimmune uveitis (EAU) in Lewis rats and subhuman primates. In order to evaluate the role of natural microbial infections in causing autoimmune diseases we have constructed a recombinant Escherichia coli expressing retinal S Ag when injected it into Lewis rats which developed EAU. Control animals immunized with E. coli JM105 transfected with only plasmid DNA did not induce EAU. Similarly, baker's yeast (Saccharomyces cerevisiae), which has six amino acid residues in histone H3 identical with peptide M of S-Ag, induced EAU when injected into rats. Lymph node cells of rats immunized with recombinant E. coli or with the yeast show significant proliferative responses against peptide G and peptide M of S-Ag, respectively. The animals immunized with recombinant E. coli also produced antibody to S-Ag. PMID- 8462113 TI - Differential requirement for humoral factors for IL-2R expression of murine T cell subsets, Th1, Th2, and CD8Th clones. AB - Three types of alloreactive T helper (Th) cell clones, Th1, Th2, and CD8Th, were examined for the requirement of costimulatory factors for IL-2 receptor (IL-2R) expression and proliferation. When stimulated with allogeneic spleen adherent cells, these Th cell clones all expressed IL-2R strongly, whereas they expressed the receptor only weakly when subjected to allogeneic B cell stimulation. The addition of partially purified IL-2RIF to Th1, Th2, or CD8Th cell clones stimulated with B cell antigen-presenting cells increased the IL-2R expression of Th1 and CD8Th cell clones but not of the Th2 cell clone. Conversely, IL-1 up regulated IL-2R expression of Th2 cell clones stimulated with B cell APC but not of Th1 and CD8Th cell clones. Neither IL-2RIF nor IL-1 induced IL-2R expression of unstimulated Th cell clones. IL-2R expressed in the presence of these costimulators contributed to IL-2-dependent proliferation of these cells. Thus, the expression of IL-2R was indicated to be regulated differently in three types of Th cell subsets through different cytokines. PMID- 8462114 TI - TNF production and hypertrophic scarring. AB - The percentage of TNF alpha- and beta-positive cells was analyzed in hypertrophic scar (N = 13), normotrophic scar (N = 7), and normal skin (N = 6) biopsies using monoclonal antibodies and immunoperoxidase staining of cryostat tissue sections. Samples were first characterized for infiltrating cells. In hypertrophic samples there was a significant increase in activated infiltrating cells, capable of producing TNF beta and IL-1 beta. In contrast, the percentage of TNF alpha positive cells was significantly lower than that detected in normotrophic scars. In fact, in hypertrophic scar samples a positive staining with anti-TNF alpha mAb was restricted to 8% of tissue-infiltrating cells compared to 35.4% of the cells present in normotrophic scars; 12% of infiltrating cells were stained in normal skin sections. These results suggest that TNF alpha may be important for normal wound healing and that hypertrophic scarring might be partially a consequence of a low amount of TNF alpha. PMID- 8462115 TI - Delineation of the role of a Na+/Ca2+ exchanger in regulating intracellular Ca2+ in T cells. AB - One of the metabolic events that results from ligation of the CD3-TCR is an increase in [Ca2+]i. The mechanisms that generate this rise in [Ca2+]i are poorly understood, but involve mobilization of intracellular Ca2+ stores and the movement of extracellular Ca2+ into the cell. To examine the role of Na+/Ca2+ exchange in the increase in [Ca2+]i after CD3-TCR engagement, the effects of specific inhibitors of Na+/Ca2+ exchange, DCB, CBDMB, and bepridil, were examined. Inhibitors of Na+/Ca2+ exchange suppressed IL2 production and the rise in [Ca2+]i in Jurkat cells stimulated by anti-CD3 mAb. Mobilization of intracellular Ca2+ stores and mitogen-stimulated inositol phosphate production were not inhibited by these agents. Inhibitors of Na+/Ca2+ exchange also inhibited mitogen responses of normal T cells and the sustained increase in [Ca2+]i resulting from cross-linking class I MHC molecules, addition of PHA, or anti-CD3 mAb. Additional evidence for an important role of a Na+/Ca2+ exchanger in generating increases in [Ca2+]i after CD3 ligation was the finding that replacing extracellular Na+ with Li+, that cannot be transported by the Na+/Ca2+ exchanger, nearly abrogated the rise in [Ca2+]i induced by cross-linking CD3. These results are consistent with the conclusion that a Na+/Ca2+ exchanger is important in regulating changes in [Ca2+]i that are critical for T cell activation. PMID- 8462116 TI - An ultrastructural study of mitotic chondrocytes in the Swarm rat chondrosarcoma. AB - The Swarm rat chondrosarcoma is a well established model system for the biochemical studies of cartilage proteoglycans. In this study, we observed the ultrastructure of mitotic chondrocytes in this tumor to confirm whether it is also useful as a morphological model system to examine the mitosis of chondrocytes. As a result, the mitotic chondrocytes in this tumor contained fairly prominent cell organelles, and the endoplasmic reticulum was mainly vacuolized and the Golgi stacks were replaced by the cluster of small vesicles during the later stage of the mitotic cycle. Although the cytoplasmic division began at the telophase, the cytoplasmic cleavage furrow was so narrow that dividing chondrocytes looked as if they were partitioned by a slit. These findings are almost consistent with the changes that occurred in the mitotic chondrocytes of the tibial growth plate, although the degree of disorganization in the Golgi apparatus is slightly different. Therefore, this tumor is useful as a convenient morphological model system to examine the mitosis of chondrocytes because of the facility for taking specimens. PMID- 8462117 TI - Mechanical properties of artificial teeth. AB - In selecting the teeth for fabrication of complete or partial dentures, each patient's anatomic and physiologic requirements and the properties of the artificial teeth themselves should be taken into consideration. The purpose of this study was to evaluate the mechanical properties of the artificial teeth by the static compression test and the impact test. Specimens were the lower first molar porcelain and resin teeth (Livdent FB-20 teeth by G. C. Co., Tokyo, Japan). All were of the same shape. In the static compression test, the fracture load and deformation of the artificial teeth were measured with an Instron-type universal testing machine at a cross-head speed of 1.0 mm/min. Elastic modulus, ultimate strength and absorbed energy were calculated. In the impact test, the acceleration of a falling impactor was measured with a drop impact apparatus. The load applied to the specimen was equivalent to 300N. Absorbed energy and deformation were calculated. The resin teeth showed a lower elastic modulus, higher fracture toughness and shock-absorbing ability than the porcelain teeth. Resin teeth should be selected when the first requisite is high shock-absorbing ability, and porcelain teeth should be selected when the first requisite is high masticating efficiency. PMID- 8462118 TI - Study on morphology of mandibular corpus and ramus influencing the eruption of mandibular first permanent molar. AB - The mandibular first permanent molar has been reported to be the first permanent tooth to erupt. However, according to the recent reports, a considerable increase in the number of children has been observed with the eruption of the mandibular first permanent molar after the eruption of the mandibular central incisor. The purpose of this study is to investigate whether there is any morphological difference in the mandible including the mandibular corpus and the ramus between the subjects with the mandibular first permanent molar erupting prior to the mandibular central incisor (Group A) and the subjects with the mandibular central incisor erupting prior to the mandibular first permanent molar (Group B). Lateral, posteroanterior, 45-degree oblique cephalometric radiographs and dental plaster models were used as the materials. Based on the data statistically analyzed, the results are summarized as follows: 1. No significant differences were found in the conventional angular lateral cephalometric measurements between the two groups. 2. No significant difference was found in the mandibular length between the two groups. 3. Significant differences were found in the mandibular corpus and the ramus between the two groups. In other words, the children in Group A have a narrower ramus, longer corpus and a larger eruption space for the mandibular first permanent molar than the children in Group B. These results indicate that even though there was no significant difference in the anteroposterior dimension of the mandible between the two groups, the internal proportion of the mandible represented as the ratio between the corpus and ramus was significantly different. This may suggest that the different proportional constituents of the mandible have a close relationship with the eruption timing of the mandibular first permanent molar. PMID- 8462119 TI - Joint epidemiological longitudinal dental survey in Nigeria, especially in comparison with that of Japanese. AB - Since 1980 we carried out a longitudinal dental survey in Ile-Ife, as a joint study with the dental school of Ife University, Nigeria, being supported by A Grant under The Monbusho International Scientific Research Program for ten years. One thousand one hundred seventy-one children and adults were examined in the 1991 survey. The data were compared with the data in the previous survey and Japanese survey. Results were as follows: 1) Caries prevalence rate and the average number of DMFT were still very low, especially showing that both the caries prevalence and the average number of DMFT decreased in the rural areas because the attrition proceeded faster than the caries, 2) Nigerian deciduous and permanent dentition were larger than in the Japanese in all items measured, 3) the condylar head was transformed from the round shape to the ultra-flat shape with age, 4) there was a fewer incidence of severe periodontal diseases despite of the marked deposition of calculus, 5) with respect to Nigerian foods, there was no difference between the rainy and dry seasons in both the urban and rural communities, 6) the weaning period of the baby is decided by their mother, taking care of the health of the baby, almost all babies at one year to two years and a few at three years and 7) the menu for the breakfast, lunch and supper of the baby was made considering the nutritional aspect of the baby. PMID- 8462120 TI - Reversal of multidrug resistance in Friend leukemia cells by dexniguldipine-HCl. AB - Dexniguldipine-HCl (DNIG)--a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MDR)--was evaluated in a drug accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR), or mitoxantrone (MITO) in resistant F4-6RADR cells to the very levels observed in drug-sensitive F4-6 precursor cells. In parallel with the increase in DNR content (F4-6RADR, solvent: 303 +/- 27 pmol/mg protein; DNIG (3.3 mumol/l): 1,067 +/- 174 pmol/mg protein; F4-6P, solvent: 948 +/- 110 pmol/mg protein; n = 8 9, SEM), the amount of DNR tightly bound to the acid precipitate pellet obtained from F4-6RADR (i.e., protein, DNA, RNA) increased 3.9-times to the levels observed in sensitive F4-6 cells. The main pyridine metabolite of DNIG displayed similar activity. Concentration-response analysis revealed that DNIG and R,S verapamil (VER) induced 100% reversal of the DNR accumulation shortage associated with the MDR phenotype but DNIG was 8 times more potent than VER (50% inhibitory concentration (IC50), 0.73 vs 5.4 mumol/l). In keeping with the accumulation assay, DNIG was about 10 times more potent than VER in sensitizing F4-6RADR cells to the cytostatic and cytotoxic effects of DNR in proliferation assays. In conclusion, DNIG is a potent in vitro modulator, improving (a) the accumulation of anthracycline-like cytostatics, (b) drug access to cellular binding sites, and (c) the cytostatic action of DNR in F4-6RADR leukemia cells of the MDR phenotype. PMID- 8462121 TI - Effect of tumor presence on cisplatin and carboplatin: disposition in the isolated, perfused tumor and skin flap. AB - The purpose of this study was to evaluate the disposition of elemental platinum (Pt) derived from cisplatin (CDDP) or carboplatin (CBDCA) in the isolated, perfused tumor and skin flap (IPTSF). Flaps were perfused with either 3.0 micrograms CDDP/ml perfusion medium (n = 4 tumor, n = 4 control) or 15 micrograms CBDCA/ml (n = 4 tumor, n = 3 control) at a rate of 1 ml/min for 3 h. A 2-h (CDDP experiments) or 3-h (CBDCA experiments) washout phase using undosed medium was then performed. The disposition kinetics of free (ultrafilterable) Pt were characterized using a four-compartment physiologically relevant pharmacokinetic model. A tumor effect on the disposition of Pt was noted in that the Pt mass from CDDP in the central and mobile tissue compartments was greater in tumor flaps than in control flaps (P < 0.05). Similar trends were noted in CBDCA-treated flaps, but these were not significant. The Pt mass in the fixed tumor and non tumor tissue compartments was significantly greater when Pt was derived from CDDP than when it was derived from CBDCA (P < 0.05). A linear relationship existed between the estimated micrograms of Pt in the flaps from both CDDP and CBDCA and the cross-sectional vascular resistance of the flaps at 30 (CDDP, r = 0.78; CBDCA, r = 0.89) and 60 min (CDDP, r = 0.65; CBDCA, r = 0.85) of perfusion. We conclude that the IPTSF is a useful model for evaluating the disposition of Pt drugs in tumor and non-tumor tissue and that tumor presence alters the disposition of CDDP. PMID- 8462123 TI - Phase I pharmacokinetics study of high-dose fotemustine and its metabolite 2 chloroethanol in patients with high-grade gliomas. AB - The pharmacokinetics of high-dose fotemustine followed by autologous bone-marrow transplantation during a phase I-II clinical trial in 24 patients with glioblastoma or astrocytoma (grade III-IV) was investigated. Plasma levels of fotemustine were determined by high-performance liquid chromatography (HPLC) and UV detection. The metabolite, 2-chloroethanol, was simultaneously followed in six patients by gag liquid chromatography and electron capture detection (GLC-ECD) assay. The drug was given as a 1-h infusion on 2 consecutive days. In all, 40 pharmacokinetic determinations of fotemustine were made at dose levels ranging from 2 x 300 to 2 x 500 mg/m2. Plasma drug elimination was best described by a bi exponential model, with short distribution and elimination half-lives of 4.15 +/- 2.57 and 28.8 +/- 12.1 min being observed, respectively. No significant difference in half-lives or clearance was seen between the first and the second administration. During dose escalation, the mean area under the concentrationtime curve (AUC) increased from 5.96 +/- 2.89 to 12.22 +/- 3.95 mg l-1 h. Drug clearance was independent of the dose given and equal to 109 +/- 65 l/h, indicating no possible saturation of metabolism and elimination mechanisms at these high-dose levels. The metabolite 2-chloroethanol appeared very early in plasma samples. Its elimination was rapid and rate-limited by the kinetics of the parent compound, giving the same apparent terminal half-life. A close relationship between AUC and C45 values was evidenced (r = 0.890). Associated with the stability of fotemustine kinetic parameters, this could be used in future studies for individual dose adjustment, particularly for high-dose fractionated regimens. PMID- 8462122 TI - Pharmacological properties of the ornithine decarboxylase inhibitor 3-aminooxy-1 propanamine and several structural analogues. AB - Analogues of 3-aminooxy-1-propanamine proved to be highly potent and selective inhibitors of ornithine decarboxylase (ODC). The compounds competed with ornithine for the substrate binding site of ODC, but resulted in progressive and apparently irreversible inactivation of the enzyme. Diamine oxidase was inhibited by these compounds to a lesser extent than ODC; the compounds were not metabolized by this enzyme. Several derivatives were growth-inhibitory for human T24 cells and for other mammalian cells, the most active compound being 3 aminooxy-2-fluoro-1-propanamine (AFPA). Growth-arrested cells were largely depleted of putrescine and spermidine. Cellular growth arrest could be antagonized by supplementation with spermidine. Selection for resistance against AFPA led to cells with amplified ODC genes and overexpression of the message. Some of the derivatives were tumoristatic at well-tolerated doses in mice bearing solid T24 tumours. The antiproliferative activity of these compounds appears to be mediated by polyamine depletion. PMID- 8462124 TI - Doxorubicin and doxorubicinol pharmacokinetics and tissue concentrations following bolus injection and continuous infusion of doxorubicin in the rabbit. AB - Cumulative dose-related, chronic cardiotoxicity is a serious clinical complication of anthracycline therapy. Clinical and animal studies have demonstrated that continuous infusion, compared to bolus injection of doxorubicin, decreases the risk of cardiotoxicity. Continuous infusion of doxorubicin may result in decreased cardiac tissue concentrations of anthracyclines, including the primary metabolite doxorubicinol, which may also be an important contributor to cardiotoxicity. In this study, doxorubicin and doxorubicinol plasma pharmacokinetics and tissue concentrations were compared in New Zealand white rabbits following intravenous administration of doxorubicin (5 mg.kg-1) by bolus and continuous infusion. Blood samples were obtained over a 72 h period after doxorubicin administration to determine plasma doxorubicin and doxorubicinol concentrations. Rabbits were killed 7 days after the completion of doxorubicin administration and tissue concentrations of doxorubicin and doxorubicinol in heart, kidney, liver, and skeletal muscle were measured. In further experiments, rabbits were killed 1 h after bolus injection of doxorubicin and at the completion of a 24-h doxorubicin infusion (anticipated times of maximum heart anthracycline concentrations) to compare cardiac concentrations of doxorubicin and doxorubicinol following both methods of administration. Peak plasma concentrations of doxorubicin (1739 +/- 265 vs 100 +/- 10 ng.ml-1) and doxorubicinol (78 +/- 3 vs 16 +/- 3 ng.ml-1) were significantly higher following bolus than infusion dosing. In addition, elimination half-life of doxorubicinol was increased following infusion. However, other plasma pharmacokinetic parameters for doxorubicin and doxorubicinol, including AUC infinity, were similar following both methods of doxorubicin administration. Peak left ventricular tissue concentrations of doxorubicin (16.92 +/- 0.9 vs 3.59 +/- 0.72 micrograms.g-1 tissue; P < 0.001) and doxorubicinol (0.24 +/- 0.02 vs 0.09 +/- 0.01 micrograms.g-1 tissue; P < 0.01) following bolus injection of doxorubicin were significantly higher than those following infusion administration. Tissue concentrations of parent drug and metabolite in bolus and infusion groups were similar 7 days after dosing. The results suggest that cardioprotection following doxorubicin infusion may be related to attenuation of the peak plasma or cardiac concentrations of doxorubicin and/or doxorubicinol. PMID- 8462125 TI - Effect of temozolomide and dacarbazine on O6-alkylguanine-DNA alkyltransferase activity and sensitivity of human tumor cells and xenografts to 1,3-bis(2 chloroethyl)-1-nitrosourea. AB - We investigated the ability of 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC, decarbazine) and an analogue, temozolomide, to deplete cells or tumors of O6 alkylguanine-DNA alkyltransferase (AGT) and to enhance the antitumor effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Human colon cancer (HT29) cell survival was decreased by almost 1 log when treated with 500 microM temozolomide prior to 150 microM BCNU. Administration of the maximal tolerated dose of DTIC (300 mg/kg) to nude mice carrying HT29 xenografts resulted in complete depletion of AGT activity in tumors at 4 h and 16 h. Administration of 150 mg/kg DTIC caused a 76% reduction in AGT activity at 4 h, but only a 28% reduction at 16 h. The maximally tolerated doses of DTIC and BCNU, alone and in combination, were used to treat nude mice bearing HT29 xenografts. No difference in tumor growth occurred when animals were treated with either BCNU alone (50 mg/kg), DTIC alone (300 mg/kg), DTIC (150 mg/kg) followed by BCNU (12.5 mg/kg), or BCNU (25 mg/kg) followed by DTIC (150 mg/kg). These data suggest that methylating agents such as DTIC may be too toxic to be used in combination with BCNU to deplete tumor alkyltransferase levels effectively and increase the therapeutic index of BCNU. PMID- 8462126 TI - Pharmacokinetics of BW12C and mitomycin C, given in combination in a phase 1 study in patients with advanced gastrointestinal cancer. AB - The effect of combining the oxygen-transport-modifying drug BW12C with mitomycin C was investigated in a phase 1 study of 26 patients with advanced gastrointestinal cancer. The dose of BW12C was increased from 20 mg/kg to 60 mg/kg. Dose-limiting toxicity of vomiting was experienced at doses greater than 50 mg/kg. This corresponded to whole blood levels > or = 700 micrograms/ml and to > 50% haemoglobin modification. Whole blood concentrations of BW12C and modification of the haemoglobin oxygen saturation curve were linearly dependent on dose. BW12C whole blood pharmacokinetics were best described by a one compartment model and were clearly dose-dependent. The half-life increased from 2.1 h at a dose of 20 mg/kg to 7.2 h at a dose of 60 mg/kg. The AUC increased in a similar non-linear fashion with increasing dose. Mitomycin C was given at a fixed dose of 20 mg/m2 at the end of the BW12C infusion. Mitomycin C plasma pharmacokinetics fitted a two-compartment model, giving a mean beta half-life of 50 +/- 7 min and AUC of 1.1 +/- 0.08 micrograms/ml h, and were unaffected by the combined treatment. There was no evidence of increased mitomycin C toxicity. PMID- 8462127 TI - Glutathione depletion increases the cytotoxicity of melphalan to PC-3, an androgen-insensitive prostate cancer cell line. AB - Prostate cancer that is androgen-insensitive is unresponsive to a wide spectrum of cytotoxic agents, including all of the alkylating agents. Since a major pathway for the detoxification of the alkylating agents is conjugation with glutathione (GSH), GSH depletion has proved to be effective as a technique to restore melphalan sensitivity in melphalan-resistant cancer cell lines. However, the effect of GSH depletion has not been widely studied in tumor cell lines that have not developed resistance due to previous exposure to alkylating agents. Thus, we decided to investigate GSH depletion as a technique to increase melphalan cytotoxicity to PC-3 cells, an androgen-insensitive prostate cancer line. After 2 and 6 h incubation with 0.25-5 microM melphalan, virtually no effect was observed on either clonogenic lethality or MTT viability until 5 microM exposures. A 24-h incubation of the cells with 100 microM buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, reduced the GSH content by 70% 75%. Following GSH depletion, an increase in clonogenic lethality and a decrease in MTT viability occurred after exposure to concentrations as low as 0.25 microM. The dose modification factor ranged from 2.9 after 2 h incubation to 4.5 at 6 h. These results provide support for additional studies in prostate cancer for further investigation of GSH depletion as a technique to induce sensitivity to alkylating agents in this chemotherapy-resistant tumor. PMID- 8462128 TI - Oral bioavailability of mesna tablets. AB - To test the feasibility of uroprotection with sodium 2-mercaptoethane-sulfonate (mesna) in tablet form the bioavailability of mesna tablets was determined in healthy volunteers by HPLC. The area under the plasma concentration-time curve (AUC) of free mesna was significantly lower following oral (110 mumol.l-1 x h-1; 95% CI 98-122) than following i.v. administration of 1.2 g of mesna (201 mumol.l 1 x h-1; 95% CI 158-244). The AUC for total mesna, i.e. dimesna and mixed disulfides, however, were comparable in the two groups, with 628 (539-717) and 772 (713-831) mumol.l-1 x h-1, respectively. The mean residence time was significantly longer following oral mesna, at 79 (76-83) min vs 239 (229-250) min. Following oral mesna 51.1% (46.2-56.0%) of the administered dose was recovered in the urine in 24 h, compared with 60.6 (53.6-67.6)% in 4 h following i.v. mesna, and the average concentration of mesna in the urine exceeded 3 mmol.l 1 for 8 h. The data indicate that mesna in tablet form has an adequate bioavailability for uroprotection and therefore may be preferable to liquid mesna, which has an unpleasant taste. Oral mesna has a longer mean residence time than i.v. mesna, which means that uroprotection can be achieved with longer dosing intervals. PMID- 8462129 TI - Gastrooesophageal reflux in children with cerebral palsy. AB - Feeding difficulties, vomiting and recurrent chest infections associated with poor growth and nutrition are common in children with cerebral palsy (CP). However, the role of gastrooesophageal reflux as a possible cause has been little studied. We therefore investigated 23 children with cerebral palsy (median age 2.3 years, range 0.6-11.8) whose symptoms were consistent with gastrooesophageal reflux (severe feeding difficulties 70%, failure to thrive 52%, anaemia 31% and recurrent chest infections 31%). Using 24-hour ambulatory oesophageal pH monitoring, we determined the relationship between gastrooesophageal reflux and: (a) developmental age (Griffith's scales); (b) feeding behaviour skills score; (c) nutritional status and (d) clinical assessment of cerebral palsy (type and severity). Abnormal gastrooesophageal reflux (i.e. reflux index > 5%) was detected in 16 (70%) patients (median reflux index 11.4%; range 5.4-59%). Reflux was unrelated to chronological or developmental age, but there was a significant, unexplained association with male gender (P < 0.01). No correlation was found with feeding behaviour skills score, malnutrition (which was commonly severe) and type and severity of cerebral palsy. We conclude that gastrooesophageal reflux is common and should be sought in symptomatic, neurologically handicapped children as effective treatment is likely to improve quality of life. PMID- 8462130 TI - Annotation: care of children in hospital. The European Association for Children in Hospitals. AB - The Charter for Children in Hospitals, drawn up by professional and women's groups from a number of European countries at the First Conference for the Care of Children in Hospital (Netherlands 1988) presents many fine guidelines for protecting the rights of children and their parents before, during and after hospitalization. The development of these guidelines, their current acceptance in Europe and the psychological principles underlying them, are outlined here. PMID- 8462131 TI - Handedness in children at school entry: does the 'Mesker test' provide a valid method for testing writing handedness? AB - The 'Mesker test', an experiment devised after the psycho-motor dominance test described by the Dutch paediatrician Mesker, was evaluated as a method for testing writing handedness in 145 children at school entry in Crewe Health Authority. Also included in the assessment was if, and how these children know their laterality. Positive outcome was measured as Mesker test result corresponding to spontaneous hand-preference in symbol copying. The correct indication of right arm or leg was evaluated in relation to the outcome by chance. The Mesker test could not confirm hand-preference in children at school entry. There was no significant relation to the child's maturity and no significant consistency in test performance. The sub-group of right-handed writers who confirmed their handedness showed an almost significant level of consistency. No more children who thought they knew the right side indicated the correct limb then could have been arrived at by chance. This was not significantly related to having been taught, writing handedness or maturity. It is concluded therefore, that at school entry age children don't have a good knowledge of their body's laterality. Although the Mesker test does not confirm writing handedness at school entry, it may be useful in older children with inconsistent laterality. PMID- 8462132 TI - Prevention of childhood disability in the People's Republic of China. AB - With a dramatic decrease in infant mortality, an emerging challenge facing modern medicine in China is chronic disabling conditions in infants and young children. According to the results of a national sampling survey in 1987, it is estimated that there are over 51 million people of all ages with disabilities, which accounts for 4.9% of the total population. One out every five families in China has a member who is disabled. For children under 14 years of age, the overall prevalence rate of disability is 2.66%. The prevalence rate of mental retardation is 1.8% which accounts for 66% of all disabled children. Mental retardation is the most frequent childhood disability. Research on factors contributing to disability indicates the complexity of the problem. The etiology of 47% of cases is unknown, 21% of cases result from damage prenatally, 3% are due to perinatal factors, 29% are acquired during infancy and early childhood. Efforts to prevent developmental disabilities among children can be classified in terms of primary, secondary and tertiary activities. The most important primary prevention activities consist of genetic counselling, immunization programmes, improved prenatal, perinatal and postnatal health care, and legislation. On the secondary preventive level, focus is primarily on prenatal diagnosis and newborn screening. Tertiary preventive efforts include special education and comprehensive rehabilitation services. While these prevention efforts have been established, they are insufficient to meet the needs of disabled children and their families. In the context of the one child per family policy in China, much more is needed, much more can be done to reduce childhood disability. In addition to strengthening prevention efforts at all 3 levels, special emphasis should be placed on (a) integration of existing primary health care systems with early intervention programmes, (b) public education and information, (c) personnel preparation, and (d) research and evaluation. PMID- 8462133 TI - Reliability and validity of the Portage assessment scale for clinical studies of mentally handicapped populations. AB - The Finnish version of the Portage Assessment Scale was used with 114 aspartylglucosaminuria (AGU) persons aged between 1 and 56 years. Ninety-three persons with AGU were also given psychological tests, mainly SB (Finnish), WISC-R and WPPSI, but also Merrill-Palmer, Bayley, Leiter and WAIS tests. The data also include for the reliability assessment a sample of 30 normal pre-school children. The internal consistency reliability was calculated for the areas of socialization 0.80, language 0.81, self-help 0.73, cognitive 0.70, motor 0.75 and for the whole scale 0.80. The factor analysis produced one very strong factor. The results of the Portage assessment were compared to the developmental levels provided by the tests. Both methods gave almost identical cross-sectional descriptions of the skills of patients with AGU, which was interpreted as providing a cross-validation for Portage in clinical use and to mean that Portage can be used as a reasonable assessment method. The advantages of Portage include easy use by non-psychologists, concrete descriptions of the skills, the 5 areas, and the close relation to rehabilitation. PMID- 8462134 TI - Are primary school children gaining heart health benefits from their journeys to school? AB - Information was collected in relation to 1133 children, aged 4-11 years, regarding methods of travel to and from school, together with distances involved. Ninety-seven per cent of the children walked, travelled by car or alternated between these 2 methods of travel. Some 584 children (51.5%) walked to school every day with an average one-way-distance of less than half a mile. It would seem therefore that few primary school children are walking far enough to gain heart health benefits from their journeys to school. Reasons are given, however, as to why it is important for young children to be encouraged to walk to school providing adequate safety considerations are taken into account. PMID- 8462135 TI - Coronary artery size and dilating capacity in ultradistance runners. AB - BACKGROUND: Increases in coronary artery size and dilating capacity have been observed in some animals after endurance training, and at autopsy, active men appear to have enlarged epicardial coronary arteries. This cross-sectional study was designed to test the hypothesis that highly trained endurance runners have larger epicardial coronary arteries and greater dilating capacity than inactive men. METHODS AND RESULTS: The subjects, ages 39-66 years, included 11 male volunteers who had participated in ultradistance running during the past 2 years and 11 physically inactive men who had been referred for arteriography but had no visible coronary artery disease. The internal diameter of the proximal segments of each major epicardial coronary artery was measured before and after nitroglycerin administration using a computer-based quantitative arteriographic analysis system. Measurements also included maximal oxygen uptake, plasma lipoprotein concentrations, body composition, and cardiac mass by echocardiography. Before nitroglycerin, the sum of the cross-sectional areas for the proximal right, left anterior descending, and circumflex arteries was not different for the runners and the inactive men: 22.7 +/- 4.79 versus 21.0 +/- 7.97 mm2 (p = 0.57), respectively. However, the increase in the sum of the cross sectional area for the proximal right, left anterior descending, and circumflex arteries in response to nitroglycerin was greater for the runners (13.20 +/- 4.76 versus 6.00 +/- 3.02 mm2; p = 0.002). Left ventricular mass index (152 +/- 21 versus 116 +/- 41 g/m2; p < 0.05) but not left ventricular mass (284 +/- 40 versus 246 +/- 91 g; p = 0.22) was significantly greater for the runners. Among the runners, dilating capacity was positively correlated with aerobic capacity and negatively related to adiposity, resting heart rate, and plasma lipoprotein concentrations. CONCLUSIONS: Highly trained, middle-aged endurance runners demonstrated a significantly greater dilating capacity of their epicardial coronary arteries in response to nitroglycerin compared with inactive men. The causes of this greater dilating capacity and its clinical significance need to be determined. PMID- 8462136 TI - Prognostic value of an abnormal signal-averaged electrocardiogram in patients with nonischemic congestive cardiomyopathy. AB - BACKGROUND: An abnormal signal-averaged ECG (SAECG) has predictive value for arrhythmic events in patients with coronary artery disease. The purpose of this study was to investigate whether an abnormal SAECG could provide prognostic information in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: We prospectively obtained SAECGs in 114 patients with dilated nonischemic cardiomyopathy. Twelve-lead ECGs, left ventricular ejection fractions, hemodynamic measurements, and peak exercise oxygen consumption (VO2) also were measured. An SAECG was defined as abnormal by any one of the three following criteria: filtered QRS duration > 120 msec, root-mean-square voltage in the last 40 msec < 20 microV, or duration < 40 microV > 38 msec at 40 Hz. Sixty six patients had a normal SAECG, 20 patients had an abnormal SAECG, and 28 patients had bundle branch block (BBB). Mean follow-up was 10 +/- 5 months. Age, ejection fraction, peak VO2, pulmonary capillary wedge pressure, and cardiac index were not statistically different among the three groups. Use of antiarrhythmic drugs was similar among the three groups, although patients with BBB had more implantable defibrillators (p < 0.05). The incidence of previous atrial arrhythmias was similar for the three groups. Patients with abnormal SAECG or BBB had more past episodes of sustained ventricular tachycardia and/or sudden death episodes (n = 9) than patients with normal SAECG (n = 1) (p < 0.01). Prospectively, none of the 66 patients with normal SAECG died suddenly or had sustained ventricular arrhythmias. Two deaths occurred from progressive heart failure, and three patients required urgent transplant. In the 20 patients with an abnormal SAECG, four patients had sustained ventricular tachycardia, five patients died suddenly, two patients died from progressive heart failure, and one patient required urgent transplant. In the patients with BBB, four patients had sustained ventricular tachycardia, and four patients required urgent transplant. One-year event-free survival, i.e., absence of ventricular tachycardia and/or death, was 95% in patients with normal SAECG, 88% in patients with BBB, and only 39% in patients with an abnormal SAECG (p < 0.001). Multivariate analysis demonstrated that SAECG and New York Heart Association classification were independent predictors of survival. CONCLUSIONS: Patients with an abnormal SAECG had a statistically significant increase in sustained ventricular arrhythmias and/or death than did patients with a normal SAECG or BBB. This study demonstrates that an abnormal SAECG is a marker of past and future arrhythmic events in patients with nonischemic dilated cardiomyopathy. In contrast, patients with a dilated cardiomyopathy with a normal SAECG have an excellent prognosis with adverse outcome only from progressive heart failure. PMID- 8462137 TI - Effects of captopril on ischemia and dysfunction of the left ventricle after myocardial infarction. AB - BACKGROUND: Treatment with angiotensin converting enzyme inhibitors has been shown to be beneficial in patients with heart failure and myocardial infarction. Experimental studies have shown beneficial effects on the ischemic myocardium. METHODS AND RESULTS: The effects of captopril were evaluated in 64 patients with left ventricular dysfunction after myocardial infarction. The patients were randomized at day 7 to either placebo or captopril (50 mg daily) in a double blind parallel study over a period of 6 months. The patients were followed up by means of ambulatory ECG monitoring, bicycle ergometer testing, and echocardiographic examination. The duration of ST segment depression detected during ambulatory ECG monitoring was lower in the captopril group (87 minutes) than in the placebo group (638 minutes) (p < 0.001), and the number of patients in the captopril group with exercise-induced ST segment depression (p < 0.01) was lower at the completion of the study. The working capacity increased during the study period from 540 +/- 47 seconds to 738 +/- 41 seconds (p < 0.01) in the captopril group and was higher than that in the placebo group (530 +/- 43 seconds, p < 0.01) at the end of the study. Furthermore, a significant dilation of the left ventricular end-diastolic and end-systolic volumes was observed in the placebo group (p < 0.05); this was prevented in the captopril group where, in addition, a reduction in end-systolic volume was observed (p < 0.05). CONCLUSIONS: Captopril has a favorable effect on the dysfunctioning myocardium after myocardial infarction inasmuch as the ischemic burden is reduced, the working capacity is increased, dilation of the left ventricle is prevented, and systolic function is improved. PMID- 8462138 TI - Hemodynamic characteristics of the early phase of primary hypertension. The Dutch Hypertension and Offspring Study. AB - BACKGROUND: The hemodynamic characteristics of the early phase of primary hypertension are subject to debate. In particular, it remains unclear whether an increased vascular peripheral resistance or a raised cardiac output is involved as the primary hemodynamic alteration in hypertension. METHODS AND RESULTS: We studied hemodynamic characteristics and oxygen consumption in relation to 24-hour ambulatory blood pressure measurements in three groups of normotensive children with a different familial predisposition for hypertension. Selection of participants was based on parental blood pressure levels. Mean 24-hour blood pressure was higher in the offspring of two hypertensive parents compared with the offspring of two normotensive parents; there was a difference of 4.7 mm Hg (95% confidence interval [CI], 1.8-7.6) for systolic blood pressure and a difference of 4.8 mm Hg (CI, 2.3-7.3) for diastolic blood pressure. The 24-hour blood pressure pattern was consistently at a higher level for both systolic and diastolic blood pressures in the offspring of two hypertensive parents compared with the offspring of two normotensive parents. The smallest differences in blood pressure were seen at night, and the largest differences in blood pressure between the groups of offspring were seen during periods of physical activity. Echocardiographic examination combined with registration of oxygen consumption did not show a difference in cardiac index and arteriovenous oxygen difference between the study groups. However, differences in cardiac dimensions were apparent, with an increased left ventricular mass index (8.7 g/m2; CI, 2.4-15.0) in the offspring of two hypertensive parents. CONCLUSIONS: These findings do not support the existence of a hyperkinetic circulatory phase but may indicate the presence of an increased left ventricular mass in early primary hypertension. PMID- 8462139 TI - Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults. The Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Plasma levels of homocyst(e)ine are elevated in certain patients with occlusive arterial diseases. We extended these findings to asymptomatic adults. METHODS AND RESULTS: We determined plasma homocyst(e)ine levels in 287 pairs of asymptomatic adults. Cases and controls were defined on the basis of intimal medial thickness of the carotid wall as measured by B-mode ultrasound. Study subjects had no history of atherosclerotic disease and were selected from a probability sample of 15,800 men and women between 45 and 64 years old. Subjects with thickened intimal-medial carotid walls (cases) had higher plasma homocyst(e)ine levels than controls (p < 0.001). The odds ratio for having a thickened carotid artery wall was 3.15 (p < 0.001) for subjects in the top quintile of plasma homocyst(e)ine levels (> 10.5 mumol/L) compared with those in the bottom quintile (< 5.88 mumol/L). CONCLUSIONS: The present study as well as observations on the common occurrence of elevated plasma homocyst(e)ine levels in patients with occlusive arterial diseases suggest that clinical trials should be conducted to determine whether normalization of hyperhomocyst(e)inemia may prevent progression of atherosclerosis. PMID- 8462140 TI - Spontaneous occurrence of symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia in untreated patients. AB - BACKGROUND: Ambulatory outpatients (n = 150) with a history of paroxysmal supraventricular arrhythmia were studied to establish the characteristics of the first recurrence of symptomatic tachycardia (time to first recurrence, heart rate during tachycardia, and observed rhythm that was regular versus irregular) when no antiarrhythmic drug was being taken. Baseline variables were examined to assess their impact on time to first recurrence: index arrhythmia (paroxysmal atrial fibrillation [n = 37] versus paroxysmal supraventricular tachycardia [n = 113]), age (mean +/- SD, 43.3 +/- 16.1 years), female sex (n = 71), or presence of other heart or lung disease (n = 53). METHODS AND RESULTS: Transtelephonic monitoring of the ECG was used to document the rhythm during recurrences of symptomatic tachycardia. Time to first recurrence of symptomatic tachycardia and heart rate during tachycardia were measured, the observed rhythm was classified as irregular (consistent with paroxysmal atrial fibrillation) or regular (consistent with paroxysmal supraventricular tachycardia), and the hour of recurrence was recorded. Advancing age was significantly associated with a decreasing time to first recurrence (p < 0.001); the estimated increase in the hazard function was 25% with each 10 years of advancing age. After the effect of age was adjusted for, neither the classification of arrhythmia (p > 0.2), presence of other heart or lung disease (p > 0.8), nor sex (p > 0.9) was significantly associated with time to first recurrence. Among patients with paroxysmal supraventricular tachycardia, 6.5% had atrial fibrillation recorded at the next symptomatic arrhythmia; among patients with paroxysmal atrial fibrillation, 11.8% had a regular tachycardia recorded at the next symptomatic arrhythmia. There was a circadian pattern to the hour of occurrence of paroxysmal supraventricular tachycardia but not paroxysmal atrial fibrillation. CONCLUSIONS: Age is more important than other clinical variables, including the ECG classification of a paroxysmal supraventricular arrhythmia in predicting the occurrence of symptomatic arrhythmias. Arrhythmias documented by ECG during symptoms are often different from the arrhythmia documented at the time of referral, which may confound interpretation of antiarrhythmic drug effects. PMID- 8462141 TI - Lesion-to-lesion independence of restenosis after treatment by conventional angioplasty, stenting, or directional atherectomy. Validation of lesion-based restenosis analysis. AB - BACKGROUND: Since many restenosis trials include patients in whom more than one lesion is treated, analysis of the angiographic data on a "per lesion" basis might be confounded by potential correlations of restenosis among multiple treated lesions within each patient. The goals of this study were: 1) to determine whether there was any correlation in the rate of restenosis among multiple lesions that underwent conventional angioplasty, stenting, or directional atherectomy within the same patient and 2) to determine whether lesions treated in a multilesion intervention experience a different magnitude of restenosis than lesions undergoing single-lesion procedures. METHODS AND RESULTS: Of 441 patients treated by Palmaz-Schatz stenting (n = 114), directional atherectomy (n = 100), or conventional balloon angioplasty (n = 227), 67 underwent multilesion procedures involving treatment of 146 lesions. A general linear model with intraclass correlation (GLIMIC) was used to calculate the coefficient of correlation (rho) of the change in the measured minimum luminal diameter (late loss) from the time of the initial procedure to 6-month angiogram among the multiple lesions within the same patient for all 441 patients. This showed no correlation among multiple lesions within the same patient for the late loss in minimum luminal diameter (rho = -0.12 [95% CI: -0.40, 0.12]), among lesions in the same vessel (rho = 0.14 [95% CI: -0.34, 0.62]), or among different vessels (rho = -0.18 [95% CI: -0.52, 0.16]), suggesting that the magnitude of late loss is independent among multiple lesions within the same patient. There was no difference (p = 0.96) between the observed incidence of zero-, one-, and two-vessel restenosis (> or = 50% diameter stenosis at follow-up) for patients with multiple-lesion treatment and that predicted assuming lesion-to-lesion independence. Similarly, there was no difference in late loss or in the overall binary restenosis rate when single-lesion procedures were compared with multilesion procedures. Multivariable analysis of the late loss in lumen diameter (which adjusted for the effects of the acute result and the device used) demonstrated no independent effect (p = 0.20) of single-lesion versus multilesion status. CONCLUSIONS: Luminal encroachment appears to occur at independent rates among multiple lesions treated in a single patient. The observed incidence of restenosis for patients with multiple treated lesions is accurately predicted assuming independent probabilities of restenosis. Lesion-based analysis, even when including multiple treated lesions within the same patient, is thus valid for evaluating conventional angioplasty, stenting, or directional atherectomy. PMID- 8462142 TI - Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study. AB - BACKGROUND: Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein. METHODS AND RESULTS: We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10 mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women. CONCLUSIONS: We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p < 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels. PMID- 8462143 TI - Assessment of the human splanchnic venous volume-pressure relation using radionuclide plethysmography. Effect of nitroglycerin. AB - BACKGROUND: No method exists to assess human splanchnic venous function, the most important region in terms of vascular capacity. METHODS AND RESULTS: We studied 25 stable patients without heart failure or hypertension to develop a method to assess the splanchnic venous volume-pressure (V-P) relation and to determine the effect of nitroglycerin (GTN). We used blood pool scintigraphy to assess changes in regional splanchnic vascular volume (SVV) and low levels of continuous positive airway pressure (CPAP) to passively alter venous pressure and thus, SVV. We postulated that the relation between SVV and the CPAP used would reflect the capacitance of the splanchnic venous bed and that changes in the position of this relation would provide a relative measurement of any change in capacitance. In 12 patients (group 1), the splanchnic vascular V-P curves were recorded before and 2, 9, and 20 minutes after 0.6 mg sublingual GTN; in eight patients (group 2), recordings were made at similar times before and after sublingual administration of placebo; in five patients (group 3), the hemodynamic effects of CPAP were assessed by means of right and left cardiac catheterization. Right atrial and femoral venous pressures increased (p < 0.001) and cardiac output fell (p < 0.05) during CPAP. There was an apparently linear relation between CPAP and SVV (r = 0.74-0.98); SVV increased an average of 7.4 +/- 2.2% (p < 0.001) by 12 cm H2O CPAP: The splanchnic vascular V-P curves were reproducible with minimal variability in SVV (+/- 2%, p > 0.2) in group 2. After administration of GTN, the splanchnic vascular V-P curve shifted away from the pressure axis in a parallel fashion by an average of 9.4 +/- 5.4% (p < 0.001). CONCLUSIONS: We have developed a reproducible noninvasive technique that may be used to assess human splanchnic venous V-P relations. We have demonstrated for the first time in humans that GTN exerts its dilatory effect by increasing the unstressed splanchnic venous volume. PMID- 8462144 TI - Implantable transvenous cardioverter-defibrillators. AB - BACKGROUND: Implantable transvenous cardioverter-defibrillators offer a significant opportunity to decrease procedural morbidity and medical costs in the care of patients with life-threatening ventricular arrhythmias who otherwise would have required a sternotomy or thoracotomy for device insertion. The purpose of this study was to examine prospectively the safety, efficacy, and limitations associated with the use of a transvenously implanted, tiered-therapy cardioverter defibrillator with antitachycardia pacing function in a consecutive population of 84 ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) survivors. METHODS AND RESULTS: The index arrhythmia promoting transvenous cardioverter-defibrillator implantation was VF in 41 patients, VT in 27, and both VF and VT in 16. In each patient, transvenous defibrillation via a coronary sinus, a right ventricular, a superior vena caval, and/or a subcutaneous chest patch lead system was attempted. The pulsing methods used include two-electrode single-pathway pulsing or three-electrode dual-pathway simultaneous or sequential pulsing. A transvenous cardioverter-defibrillator was inserted if the defibrillation threshold (DFT) was < or = 20 J. Successful implantation of a transvenous cardioverter-defibrillator was possible in 80 of 84 (95%) patients. The mean implant DFT was 10.9 +/- 4.8 J. After cardioverter-defibrillator implantation, all patients were extubated in the operating room and sent to a standard telemetry ward for monitoring. No patient suffered a postoperative pulmonary complication or perioperative flurry of cardiac arrhythmias. Postoperative complications included lead dislodgments in eight, transient long thoracic nerve injury in one, asymptomatic left subclavian vein occlusion in two, asymptomatic small pericardial effusion in one, subcutaneous patch pocket hematomas in four, pulse generator pocket infection in one, and lead fracture in one. As experience was gained with the procedure, it was routine to discharge patients 3 days after surgery. The mean hospital stay was 6.0 +/- 2.4 days. Upon discharge, all patients returned to their prehospital activities including those with complications except for the patient with a pocket infection, who required intravenous antibiotic therapy. Patient survival using an intention-to-treat analysis was 98% over an 11 +/- 7-month follow-up period. During this time period, 31 of the 80 patients (39%) with transvenous lead systems were successfully treated by their device for sustained VT or VF. Antitachycardia pacing was used in 424 episodes of monomorphic VT and was successful in 371 (88%). All episodes of VF were aborted by the device. Antiarrhythmic drugs were used after device implantation in only eight of 80 patients (10%). CONCLUSIONS: Transvenous cardioverter-defibrillator implantation is practical in most candidates. Implant DFTs are usually low, surgical morbidity and postoperative complications are modest, therapy of VT and VF is efficient, and survival is excellent. PMID- 8462145 TI - Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation. AB - BACKGROUND: Although rupture of an atherosclerotic plaque is considered to be the cause of most acute coronary syndromes, the mechanism of plaque rupture is controversial. METHODS AND RESULTS: To test the hypothesis that plaque rupture occurs at sites of high circumferential stress in the diseased vessel, the distribution of stress was analyzed in 24 coronary artery lesions. Histological specimens from 12 coronary artery lesions that caused lethal myocardial infarction were compared with those from 12 stable control lesions. A finite element model was used to calculate the stress distributions at a mean intraluminal pressure of 110 mm Hg. The maximum circumferential stress in plaques that ruptured was significantly higher than maximum stress in stable specimens (4,091 +/- 1,199 versus 1,444 +/- 485 mm Hg, p < 0.0001). Twelve of 12 ruptured lesions had a total of 31 regions of stress concentration of more than 2,250 mm Hg (mean, 2.6 +/- 1.4 high stress regions per lesion); only one of 12 control lesions had a single stress concentration region of more than 2,250 mm Hg. In seven of 12 lethal lesions (58%), rupture occurred in the region of maximum circumferential stress; in 10 of the 12 lethal lesions (83%), rupture occurred in a region where computed stress was more than 2,250 mm Hg. CONCLUSIONS: These data suggest that concentrations of circumferential tensile stress in the atherosclerotic plaque may play an important role in plaque rupture and myocardial infarction. However, plaque rupture may not always occur at the region of highest stress, suggesting that local variations in plaque material properties contribute to plaque rupture. PMID- 8462146 TI - Quantitative adenosine 201Tl single-photon emission computed tomography for the early assessment of patients surviving acute myocardial infarction. AB - BACKGROUND: We prospectively investigated whether adenosine 201Tl tomography (SPECT) could determine the extent of coronary artery disease, the presence of jeopardized myocardium, and the risk for in-hospital cardiac events in 120 clinically stable patients early (5 +/- 3 days) after myocardial infarction. METHODS AND RESULTS: All patients had coronary angiography and SPECT in close proximity. Adenosine SPECT identified 99% of infarct-related arteries and 82% of severely stenosed (> or = 70%) noninfarct arteries. Multivessel disease was accurately predicted in 69% of patients. Sixty-five percent of stenosed noninfarct arteries had matching thallium perfusion defects, and 92% of these were reversible. The specificity of adenosine SPECT was > 90%. Thallium redistribution occurred often within infarct (59%) and noninfarct (92%) zones. The patency status of the arteries, however, did not predict the presence or extent of jeopardized myocardium. The perfusion defect size was larger (p = 0.0001) in patients with (45 +/- 18%) than in those without (22 +/- 15%) in hospital cardiac events. Furthermore, 90% of patients with events had a > or = 20% perfusion defect compared with only 38% of those without events (p = 0.0001). The positive-predictive accuracy for developing a cardiac event was 70% when the perfusion defect size was > 30%. The ischemic defect also was larger in patients with (19 +/- 14%) than in those without (10 +/- 10%) events (p = 0.001). The positive- and negative-predictive values for developing early postinfarction angina were 43% and 91%, respectively, when the ischemic defect was > 12%. CONCLUSIONS: In selected low-risk survivors of myocardial infarction, early quantitative adenosine SPECT is safe and accurate in detecting and localizing coronary stenoses, assessing the extent of jeopardized myocardium, and determining subsequent risk for in-hospital cardiac events. PMID- 8462147 TI - Angiographic and hemodynamic determinants of myocardial ischemia during adenosine thallium-201 scintigraphy in coronary artery disease. AB - BACKGROUND: Myocardial ischemia attributed to coronary steal may occur in some patients receiving pharmacological coronary vasodilation. ECG ST-segment depression is a marker of myocardial ischemia in these patients, but the factors determining the presence or absence of ischemia are not well known. METHODS AND RESULTS: To examine the angiographic, hemodynamic, and scintigraphic determinants of adenosine-induced ischemic ST-segment depression in patients with coronary artery disease, we studied 65 consecutive patients (45 men and 20 women; mean age, 65 +/- 12 years) who showed reversible perfusion defects during adenosine (140 micrograms.kg-1.min-1 for 6 minutes) 201Tl single-photon emission computed tomography. Patients with prior myocardial infarction were excluded. Ischemic ST depression occurred in one third of the whole cohort (22 of 65 patients). The presence of coronary collateral vessels (p = 0.001), systolic blood pressure at baseline (p = 0.006), and adenosine-induced anginal chest pain (p = 0.011) were the only significant independent predictors of ischemic ST-segment depression by stepwise logistic regression analysis. Rate-pressure product at baseline, systolic blood pressure, heart rate, rate-pressure product, increase in heart rate, and rate-pressure product during adenosine infusion and maximal percent stenosis were variables also significantly related to ischemic ST depression by univariate analysis but were not predictive after the three primary variables were included in the regression model. Perfusion defect size, number of diseased vessels, and age did not correlate with ST-segment depression. CONCLUSIONS: The presence of collaterals, which may predispose to coronary collateral steal, is the most significant correlate of ischemic ST-segment depression during adenosine infusion. Systolic blood pressure at baseline, which may affect the myocardial oxygen supply/demand ratio and anginal chest pain induced by adenosine, are additional variables related to ischemic ST-segment depression during adenosine infusion. PMID- 8462149 TI - Comparison of resetting and entrainment of uniform sustained ventricular tachycardia. Further insights into the characteristics of the excitable gap. AB - BACKGROUND: Resetting and entrainment have both been used to characterize the electrophysiological properties of the reentrant circuit in ventricular tachycardia. Several entrainment studies have suggested that the circuit has decremental properties, because the return cycle increases at faster pacing rates. Resetting, however, demonstrates a fully excitable gap in the majority of tachycardias. METHODS AND RESULTS: The response to resetting and overdrive pacing was analyzed in 18 ventricular tachycardias. Resetting demonstrated some duration of a fully excitable gap in 14 of 18 tachycardias. Overdrive pacing was performed at several cycle lengths with an incremental number of stimuli (1-15 beats) such that the first beat that interacted with the tachycardia (the nth beat) could be identified. The return cycles measured during resetting and the nth beat of pacing were identical (r = 0.99). At relatively long paced cycle lengths, paced beats after the nth beat resulted in a constant return cycle in most tachycardias with a fully excitable gap. At rapid paced cycle lengths, an increase in the return cycle from the nth to the nth + 1 beat was associated with progressive prolongation in the return cycle with each incremental paced beat until a longer equilibrium return cycle was reached or the tachycardia terminated in response to pacing. CONCLUSIONS: We propose that the responses to resetting and overdrive pacing with or without entrainment appear to provide conflicting information about the characteristics of the circuit because they in fact measure entirely different electrophysiological parameters. The nth beat of pacing foreshortens the excitable gap to the extent that it arrives prematurely. Subsequent paced beats interact with an altered tachycardia circuit that has had less time to recover excitability. Resetting is the interaction of a single paced beat with the tachycardia and, as such, provides a more accurate assessment of the characteristics of the unaltered tachycardia circuit. PMID- 8462148 TI - Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease. AB - BACKGROUND: Low heart rate variability (HRV) is associated with an increased risk of arrhythmic death and ventricular tachycardia (VT). The purpose of this study was to examine whether there is a temporal relation between changes in HRV and the onset of spontaneous episodes of VT in patients at high risk of life threatening arrhythmias. METHODS AND RESULTS: Components of HRV in the frequency domain were analyzed before the onset of 28 episodes of nonsustained VT (more than four impulses; duration < 30 seconds) and 12 episodes of sustained VT (> 30 seconds or requiring defibrillation) in 18 patients with coronary artery disease. Seven patients had survived cardiac arrest not associated with acute myocardial infarction, and 11 had a history of sustained VT. All frequency domain measures of HRV, i.e., total power (p < 0.001), high-frequency power (p < 0.05), low frequency power (p < 0.01), very-low-frequency power (p < 0.01), and ultralow frequency power (p < 0.05), were significantly lower before the onset of sustained VT than before nonsustained VT. Total power of HRV was also lower during the 1-hour period before the onset of sustained VT than the average 24 hour HRV (p < 0.05). An indirect correlation existed between the length of VT and the total power of HRV analyzed during the 15 minutes before the onset of VT (r = 0.54, p < 0.01). HRV had a trend toward increasing values before the onset of nonsustained VT (p < 0.01) but not before the sustained VT episodes. The ratio between low-frequency and high-frequency powers increased substantially before both nonsustained and sustained VT episodes (p = 0.06 and p = 0.05, respectively). The rate of VT or the coupling interval initiating the VT did not differ significantly between the nonsustained and sustained VT. CONCLUSIONS: Spontaneous episodes of VT are preceded by changes in HRV in the frequency domain. Divergent dynamics of HRV before the onset of nonsustained and sustained VT episodes may reflect differences in factors that can facilitate the perpetuation of these arrhythmias. PMID- 8462150 TI - Magnetic resonance jet velocity mapping in mitral and aortic valve stenosis. AB - BACKGROUND: Magnetic resonance (MR) phase-shift velocity mapping is an established method for measurement of nonturbulent intravascular flow. Shortening the echo time of the MR sequence to 3.6 msec allowed application of the technique to turbulent jet flow. The objective of this study was validation of MR jet velocity mapping in patients with cardiac valve stenosis. METHODS AND RESULTS: We used a 0.5-T Picker MR machine to measure peak poststenotic jet velocity in 15 consecutive patients recruited with known valve disease (six mitral stenosis, three of these restudied after valvoplasty, and 11 aortic stenosis). On the same day as the MR study, these patients underwent independent Doppler echocardiographic measurement of peak jet velocity. The results of 10 further MR investigations of aortic stenosis are also reported and compared with Doppler studies performed within 6 months. Of the 29 MR studies, 28 (97%) produced interpretable velocity maps, the one failure being attributed to misplacement of the imaging slice in a case of severe aortic stenosis. Agreement between MR and Doppler measurements of peak jet velocity in the recruited group was as follows: n = 18; range, 1.4-6.1 m/sec; mean, 3 m/sec; mean of differences (MR-Doppler), 0.23 m/sec; standard deviation of differences, 0.49 m/sec. CONCLUSIONS: In vivo MR peak jet velocity measurements agree well with those made by Doppler ultrasound. The technique, which is not subject to restricted windows of access and has potential for further refinements, could contribute to improved evaluation of stenoses, especially at locations where ultrasonic access is limited. PMID- 8462151 TI - Suppression of protein degradation in progressive cardiac hypertrophy of chronic aortic regurgitation. AB - BACKGROUND: The heart adapts to the volume overload of aortic regurgitation with dilation and hypertrophy. The development of left ventricular hypertrophy at the protein level is a dynamic process resulting from an imbalance between cardiac protein synthesis and degradation. The objective of the present study was to determine in vivo the relative contributions of cardiac protein synthesis and degradation to the progressive hypertrophy that occurs in response to chronic aortic regurgitation and to compare these with responses earlier in the course of this stress. METHODS AND RESULTS: Continuous intravenous infusions of [3H] leucine were administered 3 days and 1 month after surgical induction of aortic regurgitation and sham operation in rabbits. Total cardiac protein and myosin heavy chain fractional synthesis rates were obtained by analysis of plasma and protein hydrolysate data using [14C]-dansyl chloride assays. Left ventricular growth rates were determined from serial echocardiographic and postmortem left ventricular weight and protein concentration measurements; protein degradation rates were determined by subtraction of growth rates from synthesis rates. CONCLUSIONS: In comparison with sham-operated control rabbits, protein fractional synthesis rates were increased at 3 days but not at 1 month after induction of aortic regurgitation Progressive cardiac hypertrophy occurring at 1 month was caused by a decrease in protein fractional degradation rates. An increase in protein synthesis contributes only to the early phase of hypertrophy caused by acute aortic regurgitation, whereas progressive eccentric hypertrophy in chronic volume overload is due to suppression of protein degradation. PMID- 8462152 TI - Intraluminal vapor bubble induced by excimer laser pulse causes microsecond arterial dilation and invagination leading to extensive wall damage in the rabbit. AB - BACKGROUND: Previous in vitro studies demonstrated that during excimer laser ablation of aortic tissue in saline, a fast-expanding and imploding vapor bubble is formed. The present in vivo study was designed to demonstrate the formation of a fast-expanding intraluminal bubble in flowing blood and to assess any damage to the adjacent arterial wall. METHODS AND RESULTS: Excimer laser pulses (one to 10, at 55 mJ/mm2 per pulse) were delivered coaxially in the femoral and iliac arteries of nine normal rabbits. Time-resolved flash photography of dissected arteries in situ demonstrated a 50% diameter increase within 75 microseconds after the laser pulse and a subsequent invagination (150-500 microseconds) that corresponded with the temporal course of the bubble expansion (up to 3.2 mm in diameter) and implosion observed in a hemoglobin solution. One day after laser light delivery, light microscopy (47 arterial segments) showed abrasion of the internal elastic lamina, medial necrosis, and extensive dissection planes filled with red blood cells. The degree (up to 100% medial necrosis) and extent of damage (up to 1.9 mm in length) increased with the number of delivered laser pulses. CONCLUSIONS: In blood, each excimer laser pulse generated a fast expanding and imploding vapor bubble. In vivo, the intraluminal vapor bubble produced microsecond dilation and invagination of the adjacent arterial segment, which induced dissections and extensive wall damage far beyond the penetration depth of 308-nm laser light (< 100 microns). This unique pattern of extensive wall damage observed in the rabbit might explain the mechanism of dissection observed in humans and might have an impact on the acute and chronic outcome after excimer laser coronary angioplasty. PMID- 8462154 TI - Development of the pharyngeal arch system related to the pulmonary and bronchial vessels in the avian embryo. With a concept on systemic-pulmonary collateral artery formation. AB - BACKGROUND: The literature is ambiguous as to the question of the developmental background of systemic-pulmonary collateral arteries. These are found in combination with various congenital heart malformations such as pulmonary atresia. From a clinical point of view, it is of interest to know whether we are dealing with the persistence of transient embryological vessels such as ventral segmental arteries or parts of pharyngeal arch arteries or with the prenatal or postnatal recruitment of the bronchial vasculature that normally supplies the lung. This study of the embryology of the extrapulmonary and intrapulmonary vasculature aims at a better understanding of the variations in origin, course, branching pattern, and histology of collateral arteries. METHODS AND RESULTS: Serial sections of quail embryos ranging between stage HH11 and stage HH28 were incubated with a monoclonal antibody (alpha MB1) against endothelial cells and their precursors. Additional series of chick embryos were injected with india ink to study the lumenized vascular patterns. A splanchnic plexus consisting of endothelial cells and precursors is present around the foregut before the lung buds develop. This plexus expands and gives rise to the pharyngeal arch arteries, the ventral pharyngeal veins, the pulmonary vessels, and the bronchial vessels, including the intrapulmonary vessel network. During two subsequent periods, the splanchnic plexus is transiently connected to the systemic arteries and veins. The bronchial arteries and veins develop in the second period from these transient vessels. The expansion and extension of the splanchnic plexus to many organs during the formation of the bronchial vessels explains the varying course and branching pattern of the bronchial vasculature. CONCLUSIONS: These results show that we are not dealing with two or more individual vascular systems that contribute to the developing vessels of the lungs but with one vascular plexus that normally gives rise to the pulmonary and bronchial vasculature but has the potential to give rise to other systemic-pulmonary connections. PMID- 8462153 TI - Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment. AB - BACKGROUND: Clinical electrophysiology studies have used, for the most part, models of anatomic reentrant circuits to explain entrainment of ventricular tachycardia. Our studies use activation maps to directly determine mechanisms of entrainment of functional circuits that cause tachycardia. METHODS AND RESULTS: Electrograms were recorded from 192 sites on reentrant circuits in the epicardial border zone of canine myocardial infarcts during sustained ventricular tachycardia. Overdrive stimulation from different sites and at different cycle lengths was investigated. The reentrant circuits were shown to be functional, yet stimulated impulses could enter and repetitively reset the circuits (entrainment), demonstrating the presence of an excitable gap. Entrainment could occur from different stimulation sites with the stimulated impulses from each site activating the circuit with a different pattern. Entrainment, however, did not occur when the stimulated wave fronts obliterated the lines of functional block in the circuit. Fusion on the ECG occurred during entrainment when the stimulated impulses activated the ventricles concurrently with a previous stimulated impulse leaving the reentrant circuit at a different site. The first postpacing QRS was captured but not fused because it was caused by the last stimulated impulse emerging from the circuit. The first postpacing cycle length on the ECG was either equal to or longer than the overdrive cycle length depending on whether there was a fusion QRS during overdrive. The first postpacing cycle length at sites in the reentrant circuit equaled the pacing cycle length. At an appropriately short overdrive cycle length, stimulated impulses blocked in the circuit to terminate reentry. CONCLUSIONS: Functional reentrant circuits causing ventricular tachycardia can be reset and entrained. Activation maps directly show the mechanisms. PMID- 8462155 TI - Effect of prosthetic valve malfunction on the Doppler-catheter gradient relation for bileaflet aortic valve prostheses. AB - BACKGROUND: Considerable discrepancies between Doppler and catheter gradients caused by localized gradients and pressure recovery have been reported for normal bileaflet aortic valve prostheses. METHODS AND RESULTS: To examine whether this Doppler-catheter gradient relation is affected by prosthetic valve malfunction, a 19-mm CarboMedics aortic valve was simultaneously studied with continuous-wave Doppler and catheter technique in normal function and in various states of malfunction ranging from slightly restricted opening to total occlusion of one leaflet. For each functional status, peak and mean gradients were measured at eight different flow rates (cardiac output, 2.0-6.0 L/min). Excellent correlation between Doppler and catheter gradients was found regardless of the valve function (r = 0.99, SEE = 1.0-3.3 mm Hg). However, the relation between Doppler and catheter gradient was highly dependent on the function of the valve as shown by a variation of slopes from 1.08 to 2.08. For the normally functioning valve (angle between flow axis and leaflet 5 degrees), peak and mean Doppler gradients were approximately twice the catheter gradients (slope, 2.08 and 2.03 for peak and mean gradients, respectively). Slightly restricted opening of one leaflet (22 degrees) significantly altered the Doppler-catheter gradient relation, and slopes decreased to 1.69 (p < 0.01) and 1.52 (p < 0.001) for peak and mean gradients, respectively. The differences between Doppler and catheter gradients significantly decreased with further restriction of valve opening, and slopes ranged from 1.25 to 1.41 for angles between 34 degrees and 52 degrees. When one leaflet was totally occluded, the slope finally dropped to 1.08 for both peak and mean gradients, and Doppler gradients were only slightly greater than catheter gradients. Gradients increased with malfunction of the valve caused by reduction of the effective orifice area. However, the increase of Doppler gradients was considerably smaller than the increase of simultaneous catheter gradients. CONCLUSIONS: The discrepancies between Doppler and catheter gradients that have been reported for normally functioning bileaflet aortic valve prostheses may be reduced or even disappear in patients with malfunctioning valves. Furthermore, the increase of Doppler gradients caused by malfunction of the valve may underestimate the true hemodynamic changes. PMID- 8462156 TI - Cardiotoxicity of human recombinant interleukin-2 in rats. A morphological study. AB - BACKGROUND: One of the side effects of interleukin 2 (IL-2) cancer immunotherapy in humans is the vascular leak syndrome, which is frequently associated with depression of myocardial function, myocarditis, and myocardial necrosis. METHODS AND RESULTS: To investigate this cardiotoxicity, IL-2 (three doses of 5 x 10(5) Cetus units/day i.p.) was given to rats for 2, 3, or 5 days. Heart, lung, liver, spleen, and kidney tissues were studied by light and electron microscopy and with immunoperoxidase techniques. Cardiac changes consisted of focal lymphocytic and eosinophilic infiltration, myocyte vacuolization, myofibrillar loss, and necrosis. Ultrastructural alterations included swelling of endothelial cells, with dissociation of intercellular junctions, migration of lymphocytes into the interstitium, and interstitial hemorrhage and edema. Close contact between infiltrating lymphocytes, particularly large granular lymphocytes, and cardiac myocytes was often observed in areas of tissue damage. All lesions were more severe on day 5 than on days 2 and 3. Immunoperoxidase stains demonstrated asialo GM1 ganglioside antibody-positive, granular lymphocytes to be much more frequent in myocardium of IL-2-treated rats than in that of control rats. CONCLUSIONS: Although we cannot exclude the possibility of a direct toxic effect of IL-2 on myocytes, our observations suggest that the myocardial damage produced by this agent is triggered by IL-2-activated lymphocytes that exert cytolytic effects, first on endothelial cells and then on cardiac myocytes, thus producing lesions that involve both the cardiac microcirculation and the muscle cells. PMID- 8462157 TI - Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. AB - BACKGROUND: Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS: A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS: These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery. PMID- 8462158 TI - Cyclosporine A has no direct effect on collagen metabolism by cardiac fibroblasts in vitro. AB - BACKGROUND: Cyclosporine A has been implicated in the pathogenesis of myocardial interstitial fibrosis observed in heart transplant recipients. However, other confounding variables such as posttransplantation hypertension and rejection episodes may also be responsible for interstitial fibrosis development and associated abnormalities in ventricular diastolic function. Therefore, we examined whether cyclosporine A directly or indirectly affects fibrillar collagen metabolism by cardiac fibroblasts in vitro. METHODS AND RESULTS: Rat cardiac fibroblasts were isolated by collagenase digestion. Subconfluent cultures were then maintained (24 hours) in serum-containing or serum-free medium before addition of cyclosporine A (50-1,000 ng/mL). After an additional 24 hours, total procollagen synthesis, accumulation, and degradation were analyzed by measuring hydroxyproline content in the cell monolayer and in the ethanol-soluble and ethanol-precipitable fractions of the culture medium. mRNA levels for alpha 1(I) and alpha 1(III) procollagen polypeptides were assessed 2, 6, 12, and 24 hours after cyclosporine A treatment using Northern blot analysis. The results were compared with control cultures maintained in the absence of cyclosporine A. There were no differences in procollagen gene expression, total procollagen synthesis, accumulation, or degradation in cardiac fibroblasts treated directly with cyclosporine A, in concentrations up to 1,000 ng/mL, compared with untreated cells. In additional experiments, we examined whether cyclosporine A might stimulate the production of collagen regulatory substances by cardiac myocytes in culture. However, addition of conditioned media from neonatal myocytes maintained in the presence and absence of cyclosporine A (1,000 ng/mL) also had no effect on collagen deposition by cardiac fibroblasts. CONCLUSIONS: We conclude that cyclosporine A has no direct effect on collagen metabolism by cultured cardiac fibroblasts in vitro. In addition, we have excluded a paracrine effect of ventricular myocytes on collagen production in the presence of cyclosporine A. These results suggest that factors other than cyclosporine A are responsible for the interstitial fibrosis observed in cardiac allografts. PMID- 8462159 TI - Changes in diastolic function during development and correction of chronic LV volume overload produced by mitral regurgitation. AB - BACKGROUND: Mitral regurgitation (MR) causes an augmentation in left ventricular (LV) diastolic function, increasing early diastolic filling rate and decreasing LV stiffness. Whether these changes in diastolic function persist, return to normal, or become abnormal after mitral valve replacement (MVR) is unknown. METHODS AND RESULTS: Simultaneous LV echocardiography and catheterization studies were performed in six dogs in the baseline state (baseline), 3 months after creation of MR (chronic MR), and 3 months after MVR. Chronic MR caused LV dilation (end-diastolic dimension increased from 4.5 +/- 0.1 cm in baseline to 5.8 +/- 0.1 cm in chronic MR, p < 0.05) and eccentric LV hypertrophy (LV-to-body weight ratio increased from 3.6 +/- 0.2 g/kg in baseline to 4.9 +/- 0.4 g/kg in chronic MR, p < 0.05). Chronic MR caused an increase in LV early diastolic filling rate (peak rate of increase in minor-axis dimension increased from 11 +/- 1 cm/sec in baseline to 18 +/- 1 cm/sec in chronic MR, p < 0.05), did not change the time constant of myocardial relaxation (tau was 31 +/- 4 msec in baseline and 30 +/- 2 msec in chronic MR), and caused a decrease in the modulus of regional chamber stiffness from 7.7 +/- 1.2 in baseline to 2.4 +/- 0.03 in chronic MR, p < 0.05. MVR caused the resolution of LV dilation (end-diastolic dimension returned to normal [4.8 +/- 0.2 cm]), but three months after MVR, regression of LV hypertrophy was incomplete (LV-to-body weight ratio remained elevated [4.4 +/- 0.5 g/kg]). After MVR, LV early diastolic filling rate (8 +/- 1 cm/sec), the relaxation time constant (31 +/- 2 msec), chamber stiffness (7.1 +/- 1.8), myocardial stiffness (11.2 +/- 3.1), and LV end-diastolic pressure (8 +/- 1 mm Hg) returned to normal. CONCLUSIONS: The enhanced diastolic function seen in chronic MR returned to normal after correction of the chronic volume overload by MVR. PMID- 8462160 TI - Functional dissociation of cellular activation as a mechanism of Mobitz type II atrioventricular block. AB - BACKGROUND: Several mechanisms have been advanced to explain Mobitz type II atrioventricular block in the ischemically damaged His-Purkinje system. Only recently, however, has an animal model been developed to study this form of conduction defect in vivo and in vitro. METHODS AND RESULTS: Conduction defects were induced in anesthetized dogs by ischemic damage to the proximal His-Purkinje system after anterior septal artery ligation. Stable 2:1 atrioventricular block, localized within the His bundle or in the proximal bundle branches, was obtained in each dog by atrial pacing at an average rate of 239 +/- 20 beats per minute (n = 12). In vitro studies were then performed from the same hearts. Action potentials and electrograms were simultaneously recorded from the His bundle and the proximal right bundle branch at the site of damage. At slow rates of pacing (40-60 beats per minute), the action potential amplitude was 85 +/- 4 mV, and some cells (10 +/- 3%) showed dissociation from the electrical activity in the bundle. At fast rates (149 +/- 11 beats per minute), during 1:1 conduction, the frequency of cellular dissociation increased to 57 +/- 6% (p < 0.001), and the action potential amplitude decreased (-31 +/- 4%, p < 0.001). The frequency of dissociation closely correlated with the reduction in action potential amplitude (r = 0.87, p < 0.001). These changes were markedly attenuated once 2:1 block developed. The site of block was not constant but rather showed a dynamic behavior with spatial shifting in response to changes in pacing rate or the introduction of extrastimuli. CONCLUSIONS: These results indicate that in the ischemically damaged proximal His-Purkinje system, an increase in rate leads to reduced and asynchronous cellular activation before 2:1 block. The latter provides a more stable activation pattern, because the frequency of dissociation is markedly reduced. PMID- 8462161 TI - Coronary angiography: more than meets the eye. PMID- 8462162 TI - 'Ultra' coronary arteries: bigger and better? PMID- 8462163 TI - Prognostic impact of late potentials in nonischemic dilated cardiomyopathy. Potential signals for the future. PMID- 8462164 TI - Nonthoracotomy defibrillator lead systems. A welcomed addition but still a lot to learn. PMID- 8462165 TI - Myocardial ischemia during pharmacological stress testing. PMID- 8462166 TI - Hemodynamic overload and the regulation of myofibrillar protein degradation. PMID- 8462167 TI - In search of the optimized excimer laser angioplasty system. PMID- 8462168 TI - Transient entrainment of tachycardias. PMID- 8462169 TI - High stored iron levels and the risk of myocardial infarction. PMID- 8462170 TI - Infective endocarditis after transesophageal echocardiography. PMID- 8462171 TI - Transesophageal echocardiography and bacterial endocarditis. PMID- 8462172 TI - Smoking and acute myocardial infarction. PMID- 8462173 TI - Stability of plasma atrial natriuretic peptide. PMID- 8462174 TI - Prevention: the key to progress. PMID- 8462176 TI - Genetics of lipoprotein disorders. AB - Lipoproteins are circulating complexes of lipids and proteins, the transport and metabolism of which are directly controlled by apolipoproteins A-I, A-II, A-IV, B, C-I, C-II, C-III, D, E, and (a); lipoprotein-processing proteins lipoprotein lipase, hepatic lipase, lecithin-cholesterol acyltransferase, and cholesteryl ester-transfer protein; and lipoprotein receptors, low density lipoprotein (LDL) receptor, chylomicron remnant receptor, and scavenger receptors. Studies have shown a close association between lipoprotein abnormalities and coronary artery disease susceptibility. Four types of abnormalities are frequently seen: increased LDL cholesterol levels; decreased high density lipoprotein cholesterol levels, usually accompanied by increased triglyceride or very low density lipoprotein levels; increased concentrations of chylomicron remnants and intermediate density lipoproteins; and increased concentrations of an abnormal lipoprotein, lipoprotein (a). One or more of these abnormalities is present in 50 80% of myocardial infarction survivors. The exact pathogenic process whereby each of these abnormalities causes coronary artery disease is a subject of active investigation but beyond the scope of this brief presentation. However, the genetic contribution to each of these abnormal lipoprotein phenotypes is coming into focus and is discussed. PMID- 8462175 TI - Phenotyping. On reaching base camp (1950-1975). AB - The search for plasma lipoproteins began at the turn of the century. It was not until 1949 that a meeting of the Faraday Society celebrated the separation of the alpha and beta lipoproteins. At that moment, ultracentrifugists in Berkeley were already busily converting "alpha" to high density lipoprotein and "beta" to low density lipoprotein; the modern era of lipoproteins had begun. Over the succeeding 10 years, a quarrel over whether the level of Sf 0-20 or cholesterol was the more powerful risk factor ended with an eclipse of the analytical ultracentrifuge and a surge of interest in the biological side of lipoproteins. The postheparin clearing factor became lipoprotein lipase, and free fatty acids were discovered. In 1960, abetalipoproteinemia and Tangier disease suggested that the apolipoproteins must be specific and spurred a hunt for their number and nature. The first amino acid sequences aroused speculation of "amphipathic helices." By 1970, conversion of hyperlipidemia to five types of hyperlipoproteinemia led to worldwide fascination with electrophoretic patterns, "floating beta," and "the Friedewald formula" as codes for genetic abnormalities leading to early coronary artery disease. A few years later, the appearance of "familial combined hyperlipidemia" confounded the phenotyping, and the discovery of the low density lipoprotein receptor heralded the coming of true genotypes. This is a Bethesda-based story of the "climb to base camp" preceding the joining of molecular biology with the research on lipoproteins, dyslipoproteinemia, and atherosclerosis. PMID- 8462177 TI - Heterogeneity of high density lipoprotein particles. AB - Human high density lipoprotein (HDL) contains at least two types of lipoprotein containing A-I particles: one contains both apolipoproteins (apo) A-I and A-II (Lp A-I:A-II) as main protein components, whereas in the other, apo A-II is absent (Lp A-I). The two subpopulations have different metabolisms and physiological roles. Studies indicate that apo A-II is an antagonist of cholesterol efflux. Lp A-I but not Lp A-I:A-II is increased in women compared with men. The lower apo A-I levels in patients with coronary artery disease reflect a decrease in Lp A-I. Lp A-I also is decreased in children with a family history of coronary artery disease, and increased in elderly subjects. Despite cholesterol intake remaining constant, a high polyunsaturated:saturated fat diet leads to a decrease in Lp A-I but not Lp A-I:A-II. Chronic alcohol consumption induces an increase in Lp A-I:A-II and a decrease in Lp A-I, although short bouts of drinking produce increases in both Lp A-I and Lp A-I:A-II. Hypolipidemic drugs have specific effects on discrete apo A-I particles. PMID- 8462178 TI - High density lipoproteins, reverse transport of cholesterol, and coronary artery disease. Insights from mutations. AB - BACKGROUND: The reverse cholesterol transport model is most widely used to explain both the role of high density lipoproteins (HDL) in lipid metabolism and the inverse association between HDL cholesterol plasma concentration and the risk for coronary artery disease (CAD). As familial HDL cholesterol deficiency is frequently paralleled with a family history of premature CAD, much interest has been directed toward the molecular defects in apolipoproteins and lipid-transfer enzymes involved in the formation and metabolism of HDL. Knowledge of the basic defects in rare HDL-deficiency syndromes and apolipoprotein variants provides genetic markers of whether the presence of these molecular defects accounts for low HDL cholesterol levels and the accompanying coronary risk. METHODS AND RESULTS: Sequence analysis of proteins or DNA from patients with HDL deficiency or hyperalphalipoproteinemia as well as from randomly screened probands has helped to identify a series of molecular defects in the genes of apolipoprotein (apo) A-I, apo A-II, apo A-IV, apo C-III, lecithin cholesterol acyltransferase, and cholesterol ester-transfer protein. Some of these mutations were associated with absent and low levels of HDL cholesterol in homozygous and heterozygous carries, respectively, but only a few homozygotes were at an increased risk of CAD. These mutations were invaluable for gaining insight into structural functional relations in HDL metabolism. CONCLUSIONS: Mutations in the genes of apo A-I, apo A-II, apo A-IV, apo C-III, lecithin cholesterol acyltransferase, and cholesterol ester-transfer protein can influence HDL cholesterol plasma concentrations but do not account for the coronary risk associated with low HDL cholesterol levels. In general, these observations suggest that the low HDL concentrations in CAD patients are not a reflection of impaired reverse cholesterol transport but rather of some other metabolic disturbances, such as catabolism of triglyceride-rich particles. PMID- 8462179 TI - Genetic determinants of responsiveness to the HMG-CoA reductase inhibitor fluvastatin in patients with molecularly defined heterozygous familial hypercholesterolemia. AB - BACKGROUND: In familial hypercholesterolemia, plasma lipoproteins can be modulated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, although the underlying response mechanisms are still unknown. METHODS AND RESULTS: A single-blind study with fluvastatin, an HMG-CoA reductase inhibitor, was conducted in 64 familial hypercholesterolemia patients who had defined apolipoprotein E (apo E) and apolipoprotein(a) [apo(a)] isoforms. Plasma lipids and lipoproteins were analyzed throughout the study. The patients were grouped according to low density lipoprotein (LDL) receptor genotype. After 4 weeks of treatment with 40 mg of fluvastatin, the mean decrease in plasma LDL cholesterol (LDL-C) in patients with the genetically characterized "Sephardic" and "Lithuanian" mutations was 16-18%, whereas in the other three groups, it was 25-30% (p < 0.005). High density lipoprotein cholesterol (HDL-C) levels increased in all groups. Multivariate analyses suggested that 41% of the LDL-C response can be explained by the LDL receptor mutation, body mass index, apo E3/E4 phenotype, apo(a) isoform LpS2, and baseline LDL-C levels, and 46% of the change in HDL-C is associated with age, sex, body mass index, baseline HDL-C, and the Sephardic mutation. CONCLUSIONS: Fluvastatin exhibits diverse and independent effects on plasma lipoproteins related to several constitutional, genetic, and familial factors. Information regarding these factors may provide better prediction of patients' clinical responses to fluvastatin. PMID- 8462180 TI - A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin. AB - Disorders associated with the overproduction or delayed clearance of beta-very low density lipoprotein and low density lipoprotein (LDL) are strikingly related to premature coronary artery disease. There are five recognized classes of LDL lowering drugs, each acting through different basic mechanisms. The increased predictability, safety, and efficacy of newer lipid-lowering agents have allowed controlled clinical trials to demonstrate conclusively that reducing LDL leads to a reduction in coronary artery disease. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is almost completely absorbed, actively targeted to the liver, and secreted in the bile. It has no active circulating metabolites. The safety and efficacy of fluvastatin have been demonstrated in more than 2,500 subjects treated in the United States, Canada, and Europe, and more than 1,000 have been treated for more than 1 year. Combination of fluvastatin with cholestyramine results in additional cholesterol lowering. The Lipoprotein and Coronary Atherosclerosis Study, a randomized, double-blind trial of fluvastatin using quantitative coronary angiography to measure atherosclerotic plaque change and positron emission tomography to evaluate myocardial perfusion (myocardial flow reserve), illustrates the further exploration of lipoproteins and atherogenesis made possible by the availability of this new generation of cholesterol-lowering agents. PMID- 8462181 TI - Dyslipidemia and atherosclerosis. A forecast of pharmaceutical approaches. AB - Five classes of lipid-lowering drugs are approved by the Food and Drug Administration (FDA) for use in the United States: nicotinic acid, bile acid sequestrants, fibric acid derivatives, reductase inhibitors, and probucol. None of the agents has an antiatherosclerotic indication. Cholestyramine and gemfibrozil have received indications for preventing complications of atherosclerosis, namely, myocardial infarction and coronary artery disease death. Foreseeable pharmacological strategies to reduce lipid-related cardiovascular risk might be divided into three categories. First, the present approach of lowering lipid and lipoprotein concentrations might be extended through modification of available agents (e.g., a more potent or soluble bile acid resin) or development of agents of novel mechanism (e.g., acyl-CoA:cholesterol acyltransferase [ACAT] inhibition or inhibition of cholesterol biosynthesis at a step other than HMG-CoA reductase). Second, blood lipids could be directly addressed outside of lipid-lowering strategies. Raising high density lipoprotein (HDL) cholesterol levels has not been fully explored, or the target might be modification of the lipoproteins themselves rather than their concentrations. Areas of particular interest in the latter regard are hepatic lipase activity, cholesteryl ester transfer protein activity, and differences between oxidized or otherwise modified low density lipoprotein (LDL) particles and normal LDL. Third, it may be possible to directly lessen the atherosclerotic potential of the vessel wall (e.g., through protecting it from the effects of certain growth factors or altering its state of relaxation. PMID- 8462182 TI - Norcolut with immune modulators in the complex treatment for hyperplastic uterine processes. AB - The results are presented of the treatment of 55 patients for hyperplastic endometrial processes with the preparation norcolut combined with the immune modulators thymalinum and myelopidum. It was found that the application of the suggested schemes of the introduction of the medicines mentioned increase the treatment effectiveness and enlarges its possibilities. PMID- 8462183 TI - The significance of the relationship between serum levels of cobalamin and MCHC during pregnancy. AB - Cobalamin concentration and mean corpuscular haemoglobin concentration (MCHC) were found to have highly significant inverse correlation with the weeks of pregnancy (respectively -.278 P < .0001 and .342 P < .00001) in 205 pregnant women. Among all haematometric parameters cobalamin concentrations during pregnancy only correlates with MCHC (P < .01). This datum seems to indicate an influence of B12 on erythropoiesis which adequate the concentration of haemoglobin to circulatory modifications of pregnant women. PMID- 8462184 TI - Infectious morbidity in gynecologic oncologic surgery. A clinical and economic evaluation. AB - In the Department of Obstetrics and Gynecology, Faculty of Medicine, Varese, between March 1991 and February 1992, 70 consecutive patients undergoing elective oncologic surgery were evaluated for rationalizing the use of antibiotics in order to reduce the cost of infectious complications. We divided our patients into two groups: a high infection risk group and a low infection risk group. Our findings show that: the HIR group shows a higher antibiotic cost than LIR one; our selection criteria for HIR patients are probably correct; in the LIR group 46.6% of patients were not submitted to any antibiotic therapy. PMID- 8462185 TI - Immunoglobulins IgG, IgA, IgM, complement C3, C4 and ferritin and transferrin levels in serum and follicular fluid in IVF patients. AB - Serum and follicular fluid immunoglobulin (IgG, IgA, IgM) and complement (C3, C4), as well as transferrin and ferritin concentrations were measured in 82 consecutive IVF patients (Pregnant: Group A, and non pregnant: Group B). Higher serum concentrations were observed in complement in all Immunoglobulins but IgM which was found to be significantly lower in follicular fluid in both groups. Also there were no statistically significant differences observed for transferrin and ferritin levels in either compartment or among the groups. No correlation was found for the above parameters and the in vitro fertilization outcome in terms of oocytes retrieved, fertilized and embryos implanted. PMID- 8462186 TI - The prevalence of the precancerous lesions in breasts contralateral to clinical cancer. A morphological comparison with breasts containing a benign lump. AB - Two small series (nine cases each) of human female breasts were collected to compare the morphological changes of mammary glandular trees contralateral to primary breast cancer and those collateral to symptomatic benign lump. Each whole mammary gland was analysed by a submacroscopic scrutiny method using a stereomicroscope. Interesting and suspicious samples were removed for routine histology. Benign subclinical lesions were indifferently present in both series: Spheric cysts (5:5), sclerosing adenosis (3:3), intraductal papillomas (1:1), fibroadenomas (3:1). On the contrary proliferative epithelial lobular lesions with various degree of atypia i.e. atypical lobules (Grades IV-V according to Wellings), were detected only in the first series (p < 0.01). These data agree completely with the hypothesis of a systemic nature of breast cancer and support indirectly the possible predictive value of atypical lobules in bioptic specimens for the subsequent development of cancer in collateral and/or contralateral breasts. PMID- 8462187 TI - Sperm dysfunction in partners of infertile patients with minimal or mild endometriosis. AB - A review of the literature does not show that minimal or mild endometriosis unquestionably causes infertility although its association is known; the cause only becomes apparent as the disease progresses. In these patients therefore, prolonged infertility for other reasons may have exacerbated or predisposed a tendency in them to develop the disease. Sperm dysfunction in their partners may have been one factor. Sperm penetration assays using mid-cycle (estrus) bovine cervical mucus were studied in 22 men whose wives were confirmed to have minimal or mild endometriosis. All men had normal semen analyses. For controls, 16 men of proved fertility were used. Whilst all but one (94%) of the fertile men showed adequate penetration (> 30 mm), only 59% of the men in the study group achieved this penetration (p < 0.05). These findings provide evidence that minimal or mild endometriosis may not be the primary cause of infertility in patients in whom the diagnosis is made. PMID- 8462188 TI - Salivary ferning and the menstrual cycle in women. AB - The Authors report the data relative to the monitoring of menstrual cycle carried out by the observation of salivary ferning. They compared the usual physical and hormonal parameters of four groups of women with the aspect of the crystallisation of the saliva observed both by normal optical microscope and by a special type of pocket microscope which can be used by women themselves. In conclusion the Authors report a careful examination of the biochemical correlation relating the women's hormonal climate and its salivary constituents. PMID- 8462189 TI - Resuscitating fresh stillbirths. AB - Guidelines for duration of resuscitation of freshly-stillborn term infants and their long term outcome are unclear. The predictive factors of both cerebral palsy and early neonatal demise include Apgar scores of 3 or less at 10 minutes, perinatal acidaemia and neonatal seizures. We describe the case of severe perinatal asphyxia (umbilical artery pH at birth of 6.75, Apgar scores of 0.1 and 5 0.1 5 at 1.5 and 10 minutes and neonatal hypertonia) in a term pregnancy, where the infant made an uneventful recovery and was discharged home well. Guidelines for neonatal resuscitation are discussed. PMID- 8462190 TI - Treatment of idiopathic infertility with testosterone undecanoate. A double blind study. AB - This study refers to 50 couples treated for subfertility. Twenty five of these patients were treated with TU (Testosterone Ur econoate), the remaining 25 received placebo. Sperm characteristics, including ejaculate volume, pH, sperm density, morphology, motility, total testosterone, FSH, LH, DHT and E2 were evaluated both before and after treatment. A statistically significant increase of DHT levels was noticed after TU administration, whereas a marginally significant improvement of sperm morphology was present. Serum FSH concentrations, decreased significantly in the TU group whereas serum LH presented a slight but not statistically significant decrease; 4 pregnancies were achieved by the TU group whereas none were achieved by the patients belonging to the placebo group. The administration of TU per os to patients with idiopathic oligospermia presents a demonstrably positive effect. PMID- 8462191 TI - Characterization of a deleted Y chromosome in a male with Turner stigmata. AB - A 46,X,+mar karyotype was detected in an 11-year-old male with a clinical picture characterized by obesity, short stature, bilateral cryptorchidism and coarctation of the aorta. The presence of ZFY and SRY genes was demonstrated by PCR amplification, and the origin of the marker chromosome from a deleted Y chromosome was analyzed by in situ hybridization. The proximal limits of a deletion in Yq were defined by the absence of Southern blot hybridization signals upon probing with Yq11 markers. Cytogenetics and molecular methods taken together indicate a deletion in q11.21. In addition, the loss of Yp subtelomeric sequences was suggested by the analysis of Southern blots hybridized with a 29A24 (DXYS14) probe and by the presence of coarctation of the aorta tentatively localized in Yp. The karyotype of the patient was suggested to be: 46,X,del (Y) (p11.3 q11.21). PMID- 8462192 TI - Familial occurrence of hereditary renal adysplasia with mullerian anomalies. AB - We report on a family with unilateral or bilateral renal agenesis and Mullerian anomalies (vaginal atresia or minor anomalies). This family provides support for an autosomal dominant pattern of inheritance with incomplete penetrance and variable expressivity in hereditary renal adysplasia (HRA) associated with Mullerian defects. PMID- 8462193 TI - Infant mortality in myotonic dystrophy in Saguenay-Lac-St-Jean: a historical perspective. AB - Infant mortality among children born to 373 individuals with myotonic dystrophy (MD) who lived in Saguenay-Lac-St-Jean during the period 1838 to the present time was analyzed using a case-control approach based on a population register. A statistically significant increase was found in the rate of deaths during the first week of life among children born to MD mothers (57.5%) compared to control mothers (34.8%) and MD fathers (39.1%) (p < 0.01). The stillbirth rate was not increased. The rate of mortality after the first week fell significantly in both MD and control groups during the period of observation. There was evidence of a slight selective disadvantage among this MD population. PMID- 8462194 TI - Heritable unstable DNA sequences and hypermethylation associated with fragile X syndrome in Japanese families. AB - Fragile X syndrome, associated with the fragile site at Xq27.3 (FRAXA), is the most common form of familial mental retardation. The fragile X mutation has recently been characterized as a heritable unstable DNA sequence, p(CCG)n/p(CGG)n, in the FRAXA locus. In the present study, a correlation between fragile X-genotypes in the FRAXA locus and hypermethylation of an adjacent CpG island was examined in four Japanese families with fragile X syndrome. We show here that the heritable unstable DNA sequences in the fragile X chromosome usually increase in size when transmitted by female carriers, and that the degree of methylation in the CpG island correlated with the increased sizes of the unstable DNA sequences. When a hypermethylated full mutation was transmitted by a male to his daughters, both the size of the unstable DNA sequence and the degree of the methylation reduced to the premutation range. Our observations suggest that female meiosis has a greater potential for amplifying unstable DNA sequences and that amplified DNA sequences can be transmitted through germ cells, while male germ cells seem not to be able to tolerate highly amplified unstable DNA sequences. PMID- 8462195 TI - A balanced autosomal translocation (3;9) associated with primary hypogonadism and dorsal spine stenosis. AB - A man with a balanced translocation between chromosomes 3 and 9 associated with primary hypogonadism and dorsal spine stenosis is reported. The possible significance of this chromosomal abnormality is discussed. PMID- 8462196 TI - Trisomy 13 (Patau syndrome) with an 11-year survival. AB - Trisomy 13 is very rare in live-born children. Only a small number of these children survive the first year and very few cases are reported to live longer. Survival time depends partly on the cytogenetic findings--full trisomy 13 or trisomy 13 mosaicism--and partly on the existence of serious somatic malformations. We report on a 11-year-old girl with full trisomy 13. In this case, missing cerebral and cardiovascular malformations probably allowed the long survival. PMID- 8462197 TI - Fluorescence in-situ hybridisation and molecular studies used in the characterisation of a Robertsonian translocation (13q15q) in Prader-Willi syndrome. AB - A patient with classical Prader-Willi syndrome was found to have a Robertsonian translocation 45,XY,t(13q15q)mat. On CBG banding, the translocation chromosome had a large centromere with one primary constriction. Using fluorescence in situ hybridisation, positive signals were obtained with chromosome 13 and chromosome 15 centromere probes, proving that the translocation was dicentric. NOR banding was negative in this chromosome, suggesting that the breakpoints were at 13p11 and 15p11. DNA studies showed that, while there was no deletion involving 15(q11 13), maternal uniparental disomy for chromosome 15 was present. We compare our findings with the five other cases of familial Robertsonian translocation PWS that have been reported. PMID- 8462198 TI - Kallmann syndrome in two sisters with other developmental anomalies also affecting their father. AB - The classical features of Kallmann syndrome with anosmia and hypogonadotropic hypogonadism were observed in two sisters aged 13 and 19. They had additional malformations including anosmia, bilateral vesico-ureteral reflux and unilateral hearing loss. One of the girls had unilateral coloboma of the optic nerve. The father had unilateral hearing loss and duplication of the left ureter; he died of an unrecognized coarctation of the aorta. He had no clinical signs of hypogonadism or anosmia. It is suggested that the malformations observed in these patients may be due to a dominant inherited defect of embryonic cell migration, resulting in different phenotypic expressions within the same family, including the Kallmann syndrome. PMID- 8462199 TI - Interstitial deletion del(17) (q21.3q23 or 24.2) syndrome. PMID- 8462200 TI - Hereditary complete deficiency of the fourth component of complement: effects on the kidney. AB - Hereditary complete C4 deficiency has until now been detected in 18 patients. A disturbed clearance of immune complexes probably predisposes these individuals to systemic lupus erythematosus and other immune complex diseases. Renal involvement of hereditary complete C4 deficiency is described in seven patients from three families. Three patients of one family suffered from SLE and a severe mesangial and endocapillary proliferative glomerulonephritis which required immunosuppressive treatment. In two patients from a second family a mild focal and segmental mesangioproliferative glomerulonephritis was present which, except for an episode of acute renal failure in one patient, did not cause serious clinical problems. One additional child died without renal involvement. The patient from a third family developed Henoch-Schoenlein purpura, mesangioproliferative glomerulonephritis with segmental scarring and terminal renal failure. Immunofluorescence studies showed deposition of immunoglobulins and complement C3 in the glomeruli. Severity of renal disease is probably determined by activation of the alternative pathway of complement in the kidney. PMID- 8462201 TI - Effects of topical instillation of minocycline hydrochloride on cyst size and renal function in polycystic kidney disease. AB - To reduce renal cyst size in autosomal dominant polycystic kidney disease (ADPKD), minocycline hydrochloride solution was instilled into the enlarged cysts in three ADPKD patients. In one patient with reduced renal function, such sclerotherapy apparently diminished cyst size, but without apparent improving effect on renal function at 7 months of follow-up. The second patient, who needed the replacement therapy on admission, had been free from hemodialysis over 4 months after the therapy. Persistent flank pain disappeared in both patients. In the third patient with normal renal function, sclerotherapy was done to get a better control of hypertension. Initially blood pressure decreased, but it returned up to the pre-therapy level irrespective of definite reduction of the enlarged cysts at 8 months of follow-up. The therapy with minocycline hydrochloride did not appear harmful, and may be helpful in the management of ADPKD. PMID- 8462202 TI - Renal functional reserve in elderly patients. AB - The concept of renal functional reserve (RFR) is used in the evaluation of renal function in health and disease. RFR is defined as the difference between glomerular filtration rate (GFR) at rest and the maximum GFR for example under stimulation by an amino acid infusion or a protein rich meal. GFR decreases normally with age by about 1 ml/min per year. The purpose of this study was to establish the effect of the GFR decrease with age on absolute and relative values of RFR. We investigated 12 hospitalized patients 60 to 85 years of age (mean 74 +/- 2.0 SEM) recovering from nonrenal disease. On two consecutive days, inulin and paraaminohippuric acid (PAH) clearance was performed over a period of 4 hours. On day A patients received 1 liter of a 5% glucose solution i.v. On day B an equal volume of an amino acid solution (2 mg/kg/min) was given. In these elderly patients baseline GFR without stimulation measured 73.2 +/- 7.9 ml/min per 1.73 m2 and stimulated GFR was 99.1 +/- 8.5 ml/min, a 35.3% increase (p < 0.025). Thus, renal functional reserve measured 25.9 +/- 8.7 ml/min. PAH clearance increased from 329.0 +/- 41.9 ml/min per 1.73 m2 to 438.8 +/- 50.3 ml/min (p < 0.025). These data confirm that baseline GFR is lower in the elderly compared to young adults. However, renal functional reserve is well maintained in elderly human subjects. This suggests that glomerulosclerosis of aging may not be the only explanation for the low baseline GFR in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462203 TI - Myocardial functions of children with acute poststreptococcal glomerulonephritis. AB - Left ventricular function was investigated by two-dimensional and M-mode echocardiography in 35 patients with acute poststreptococcal glomerulonephritis and in 25 healthy controls. Six of these patients were found to have myocardial dysfunction during the acute congestive phase and convalescent phases of APSGN. One of these 6 patients, later, died. No correlations were determined between myocardial dysfunction and hypertension, cardiac failure, pericardial and pleural effusion. As a result, left ventricular function may be impaired in acute congestive phase of APSGN and this may affect the course and prognosis of the disease. PMID- 8462204 TI - Acute renal failure associated with non-fulminant hepatitis A. AB - A 49-year-old man developed acute renal failure as a complication of non fulminant hepatitis A. This is a rare association of uncertain etiology. PMID- 8462205 TI - Clinical experience with a new antithrombotic (dermatan sulfate) in chronic hemodialysis patients. AB - Dose finding studies with a new antithrombotic (dermatan sulfate) for the prevention of clot formation in the extracorporeal circuit were performed in chronic hemodialysis patients in comparison with standard heparin treatment. Dermatan sulfate (DS), which inhibits the coagulation via the heparin cofactor II pathway, was given in single predialysis injections, immediately before commencement of the dialysis procedures, in dosages ranging from 2 mg/kg to 6 mg/kg body weight. In our pilot study, an open non comparative study in patients using plate type dialyzers, we observed moderate clot formation in the extracorporeal circuit. In our second study, with a randomized heparin-controlled design in patients with plate type dialyzers, still significant clot formation occurred in the extracorporeal circuit. In the third study, in chronic hemodialysis patients using a cuprophane hollow fiber dialyzer, we also investigated the addition of a small bolus of standard heparin (20 I.U./kg body weight) to the injection of DS. A single bolus injection of 6 mg/kg, with or without the addition of a bolus of standard heparin, had a comparable efficacy as standard heparin treatment. No major bleeding events were encountered in the studies and DS had a reduced effect on the activated partial thromboplastin time as compared to standard heparin. In conclusion, these results suggest that DS in a dose of 6 mg/kg, with or without a small dose of standard heparin, given as single predialysis bolus injections, appears to be an effective alternative to standard heparin and, in addition, it may simplify the anticoagulant administration protocol. PMID- 8462206 TI - Bioelectrical impedance in the evaluation of the nutritional status of hemodialyzed diabetic patients. AB - Bioelectrical impedance is a technique allowing a quick, repeatable and reliable assessment of body composition. This method was applied to detect total body water (TBW), fat (FAT) and fat-free mass (FFM) in 80 normal subjects, 65 diabetic (45 insulin-dependent [IDD], 20 non insulin-dependent [NIDD]) and 34 uremic diabetic patients (20 IDD, 14 NIDD) submitted to hemodialysis three times a week. Uremic patients were tested at the end of the dialytic session. Multivariated analysis adjusted for age, sex and disease showed the following results: body mass index (BMI) increased with age (p < 0.005) and in the presence of NIDD (p < .001); TBW was lower in nephropathic patients (p < 0.05) and in the female sex (p < 0.0001); FFM decreased with age (p < 0.005), female sex (p < 0.0001) and in nonuremic NIDD (p < 0.001). Correspondingly FAT increased with age (p < 0.005), female sex (p < 0.0001) and in nonuremic NIDD (p < 0.001). Sixteen uremic subjects, randomly selected from both IDD and NIDD groups, tested at the beginning and at the end of the same hemodialytic session, showed a significant decrease of TBW which corresponded to the correction of their overhydratation. In our patients uremia does not seem to influence the nutritional status and the bioelectrical analysis could be applied to determine the real dry weight in hemodialyzed diabetic patients. PMID- 8462207 TI - Evaluation of maxillofacial vascular abnormalities with Tc-99m RBC. AB - Three-phase scintigraphy using Tc-99m RBC was performed in seven patients with vascular abnormalities of the maxillofacial region. Scintigraphy was able to distinguish whether the lesions had increased perfusion (three patients) or only a large venous component (four patients), and thus helped in assessing the best route for contrast angiography. In four patients a recurrence was suspected. In one, a follow-up Tc-99m RBC study showed successful embolization therapy and no recurrence, and in three patients it showed early recurrence of the lesion. The results of this report indicate the value of Tc-99m RBC scintigraphy in the management of patients with vascular abnormalities of the maxillofacial region. PMID- 8462209 TI - Bone scintigraphy in blastomycotic osteomyelitis. AB - A case of disseminated North American blastomycosis is described in which the full extent of the multifocal osteomyelitis was depicted by Tc-99m MDP scintigraphy. Skeletal involvement by this disease is not uncommon, yet the utility of bone scintigraphy has not been reported. The efficacy with which the whole body may be examined makes this technique especially appropriate for a hematogenously disseminated and often multifocal form of osteomyelitis where radiographically occult and asymptomatic lesions may be present. PMID- 8462208 TI - Evaluation of postoperative osteomyelitis of the sternum comparing CT and dual Tc 99m MDP bone and In-111 WBC SPECT. AB - This article reports on a retrospective study of 32 patients who underwent CT and combined Tc-99m MDP and in-111 WBC SPECT between 1988 and 1991 for post-operative sternal osteomyelitis. Of these 32 patients, 7 patients (Group 1) underwent evaluation for possible sternal osteomyelitis due to persistent fevers, leukocytosis, or changes in the sternal incision; 12 patients (Group 2) had surgically proven osteomyelitis, and in 13 patients (Group 3) there was definite clinical evidence of sternal wound infection (however, surgical specimens of the sternum were not submitted). There was considerable overlap between the CT findings in the soft tissues adjacent to the sternum in Group 1 and Group 2 patients. Severe demineralization was seen in two patients, and erosion of the sternum was seen in five patients with proven osteomyelitis. Combined Tc-99m MDP bone and in-111 WBC SPECT was positive for osteomyelitis in 11 of 12 patients in Group 2. One patient with osteomyelitis had negative scintigraphy; however, this patient had a four-week course of IV antibiotic therapy prior to the study. All seven patients in Group 1 had negative SPECT scans and were treated successfully with oral antibiotics and minimal soft tissue debridement. Three patients in Group 3 had negative SPECT scans and were treated successfully with antibiotics and limited debridement. Ten patients with positive SPECT scans were treated with a combination of antibiotics and aggressive surgical intervention. In conclusion, CT findings in the soft tissues offer little specificity in distinguishing soft tissue inflammation from osteomyelitis of the sternum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462210 TI - Incidental lymph node visualization on bone scan due to subcutaneous infiltration of Tc-99m MDP. A potential for false positive interpretation. AB - Soft tissue localization of radiotracer on bone scintigraphy may result in false positive interpretations, if the activity overlies a bony structure. A case is presented in which special views and follow-up clarified the soft tissue nature of focal uptake in arm and axilla. PMID- 8462211 TI - Diuresis renography. The need for an additional view after gravity-assisted drainage. AB - The role of diuresis renography (DR) in the evaluation of pelvi-ureteric junction obstruction is well established. However, problems may be encountered when applying this technique to patients after pyeloplasty because of the role of gravity-assisted drainage (GAD) in this post-operative group. Twenty-three radionuclide studies that were performed in 21 children were reviewed. All children underwent standard DR and all then had an additional view performed after GAD. In 12 children evaluated in a preoperative assessment for possible obstruction, 5 were obstructed on both DR and after GAD, 1 was equivocal on DR but drained after GAD, and 6 were not obstructed in either part of the study. In 11 children assessed after pyeloplasty, 5 were obstructed on DR but not obstructed on GAD, 3 were not obstructed in both studies, 1 was obstructed in both, and 2 were equivocal on DR but not obstructed after GAD. It can be concluded that when assessing patients, particularly those who have undergone pyeloplasty, DR should be supplemented with an additional view acquired after gravity-assisted drainage. PMID- 8462212 TI - Preoperative localization of parathyroid carcinoma using Tc-99m MIBI. AB - A patient with parathyroid cancer is presented who underwent Tc-99m MIBI scintigraphy. The Tc-99m MIBI image demonstrated increased accumulation of activity at the lower pole of the left thyroid lobe which was later confirmed as a parathyroid cancer. Uptake by parathyroid cancer must be kept in mind as a cause of increased Tc-99m MIBI accumulation when a disease is in question in the thyroid or parathyroid gland. PMID- 8462213 TI - Primary adrenocortical nodular dysplasia presented as adrenal adenoma by functional scintigraphy. AB - This is a report of a case of a 12-year-old boy with Cushing's syndrome in which high doses of dexamethasone failed to suppress glucocorticoid secretion. Neither CT nor MRI (morphologic studies) revealed any adrenal abnormality. Functional images with NP-59 (I-131 beta-iodomethyl-norcholesterol) clearly revealed intense unilateral uptake in the right adrenal gland. A right adrenalectomy was performed, and the pathologic diagnosis was primary adrenocortical nodular dysplasia. One year later, the cushingoid signs had virtually disappeared and urinary steroid excretion and serum cortisol levels were within the normal range. Nevertheless, primary adrenocortical nodular dysplasia is essentially a bilateral disease. In this case, a remission in the adrenocortical hyperfunction was observed. Although there was confusion in the etiological diagnosis, functional scintigraphy correctly indicated the status of adrenal function. PMID- 8462215 TI - Macrovascular pulmonary arteriovenous malformations demonstrated by radionuclide method. AB - Pulmonary arteriovenous malformations (AVMs) are abnormal vascular communications that allow unoxygenated blood to pass from the venous to the arterial circulation. Usually congenital in origin and twice as likely in women, hemoptysis, dyspnea, and chest pain are the common presenting complaints in AVM. A case of pulmonary AVMs that were demonstrated on a radionuclide angiogram is presented. Pulmonary AVMs were suspected after finding radioactivity in both kidneys on a perfusion lung scan. PMID- 8462214 TI - Lung uptake of Tc-99m HMPAO in cigarette smokers expressed by lung/liver activity ratio. AB - Tc-99m HMPAO, a lipophilic radiopharmaceutical used for brain imaging, has been reported to localize in smokers' lungs. To quantitate this uptake in the lung, 55 patients, who were referred for brain imaging for dementias or strokes, also underwent lung imaging (anterior lung imaging includes a large part of the liver) after IV injection of the radiopharmaceutical. Regions of interest over the liver and the lung were calculated. Of the 55 patients (ages 13-79), 30 were smokers and 25 were nonsmokers. The smokers had been smoking from 6-59 years, and daily cigarette consumption ranged from 8-50 cigarettes. The mean lung/liver ratio for smoking patients were 0.792 +/- 0.042 (SE); the mean lung/liver ratio for nonsmoking patients was 0.408 +/- 0.019 (SE). Lung/liver ratio uptake was significantly higher in the smoking patients (P < 0.01) than in the nonsmokers. Thus, lung/liver uptake of Tc-99m HMPAO may be used as an indicator of cigarette smoking. PMID- 8462216 TI - Tc-99m HMPAO brain SPECT findings in Creutzfeldt-Jakob disease. AB - A Tc-99m HMPAO brain single photon emission computed tomography (SPECT) study of a patient with biopsy-proven Creutzfeldt-Jakob disease (CJD) demonstrated decreased perfusion in the right frontal and temporal areas. Brain CT findings were normal, and electroencephalographic results were nonspecific. The clinical potential of Tc-99m HMPAO brain SPECT in the evaluation of CJD is described, and its use encouraged. PMID- 8462217 TI - Diagnosis of abdominal cerebrospinal fluid pseudocyst by scintigraphy. PMID- 8462218 TI - Vicarious excretion of technetium-99m MAG3 in a patient with polycystic renal disease. PMID- 8462219 TI - Periodontal disease detected by Tc-99m albumin colloid leukocyte imaging. PMID- 8462220 TI - Diagnosis of horseshoe kidney on technetium-99m hepatobiliary scintigraphy. PMID- 8462221 TI - Tc-99m HMPAO brain SPECT in dementia due to transitory obstructive hydrocephalus. PMID- 8462222 TI - Unintentional intraluminal small bowel catheter placement detected by Tc-99m SC scan obtained before planned intraperitoneal phosphorus-32 therapy. PMID- 8462223 TI - Radioiodine scanning of the thyroid. Searching for the other lobe. PMID- 8462224 TI - Detection of inguinal hematoma during a gastrointestinal bleeding study. PMID- 8462225 TI - Tc-99m HMPAO SPECT brain imaging of Gilles de la Tourette's syndrome. PMID- 8462226 TI - Localization of Tc-99m DTPA in a chordoma. PMID- 8462227 TI - Drug concentration monitoring. An approach to rational use. PMID- 8462228 TI - Intravenous infusion conditions. Implications for pharmacokinetic monitoring. AB - Drugs are often given intravenously with an expectation that the predicted serum concentrations will be achieved rapidly. Routine pharmacokinetic monitoring of some drugs may be of limited value, unless the effect of intravenous drug delivery systems on serum concentrations is known. In vitro studies have demonstrated that the actual time for complete drug delivery can be markedly longer than predicted and is dependent inter alia on factors including the delivery device, flow rate, injection site, drug volume and tubing diameter. Studies in paediatric patients have shown that the serum concentrations of drugs, including aminoglycosides and chloramphenicol, are strongly influenced by intravenous drug delivery systems. Similarly, data from adult patients have indicated that a drug delivery system can affect serum concentrations of aminoglycosides. Some data are available about the pharmacokinetics of drugs delivered by newer devices, e.g. controlled release infusion systems, membrane devices and implanted pumps, but additional research is needed to determine their predictability of delivery and pharmacokinetics of commonly used drugs. To achieve optimal therapeutic outcomes in patients, it is crucial to understand the impact of an intravenous drug delivery system on serum concentrations and to develop guidelines for pharmacokinetic monitoring. PMID- 8462230 TI - Famotidine and theophylline pharmacokinetics. An unexpected cimetidine-like interaction in patients with chronic obstructive pulmonary disease. AB - The results of research studies conducted to date in vitro and in healthy volunteers are practically all concordant in demonstrating the lack of any kind of interference between famotidine and microsomal oxidative metabolism. The pharmacokinetics (elimination half-life, area under the plasma concentration-time curve, clearance and volume of distribution) of theophylline 3.4 mg/kg as an intravenous infusion over 5 min (a dosage previously used to test drug interactions with cimetidine and ranitidine) were evaluated in 7 patients with chronic obstructive pulmonary disease (COPD) and peptic ulcer disease before and after 8 days' treatment with famotidine 40mg at night. The results indicate that famotidine can induce substantial and statistically significant slowing of theophylline elimination with a cimetidine-like interaction profile. PMID- 8462231 TI - Stereoselective pharmacokinetic properties of chloroquine and de-ethyl chloroquine in humans. AB - Stereoselective pharmacokinetic properties of chloroquine were investigated in humans after a single oral dose of the separate enantiomers. The study was carried out according to a crossover experimental design with a washout period between the administration of each enantiomer. Total blood chloroquine concentrations were measured using an achiral high performance liquid chromatography method. Terminal half-life (t1/2 lambda z) and mean residence time (MRT) were longer for (R)-chloroquine (294h and 388h, respectively) than for (S) chloroquine (236h and 272h, respectively). The total body clearance was lower for the (R)-enantiomer [136 +/- 38 ml/min (8.16 +/- 2.28 L/h)] than for the (S) enantiomer [237 +/- 71 ml/min (14.22 +/- 4.26 L/h)]. Although the (R) stereoisomer remained longer in the body, its volume of distribution (3410 +/- 720L) was lower than than that of (S)-chloroquine (4830 +/- 1490L). Protein binding was different for both chloroquine stereoisomers, with opposite preferential binding to human albumin and alpha 1-acid glycoprotein. Binding to total human plasma amounted to 66.6 +/- 3.3% for (S)-chloroquine and to 42.7 +/- 2.1% for the (R)-enantiomer. De-ethyl-chloroquine concentrations were also different for both enantiomers, resulting in a statistically significant increase in the AUC of (S)-de-ethyl-chloroquine (12.9 +/- 7.4 mg/L.h) compared with (R)-de ethyl-chloroquine (6.29 +/- 2.18 mg/L.h). With a daily dosage regimen, the divergent pharmacokinetic behaviour of chloroquine enantiomers generates a calculated R:S ratio of blood concentrations amounting to 1:0.7 at steady-state. Insufficient information about stereoselective activity and toxicity of chloroquine stereoisomers prevent further conclusions about the clinical consequences of these pharmacokinetic differences. PMID- 8462229 TI - Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure. AB - Arterial hypertension occurs frequently in patients with chronic renal failure. Antihypertensive treatment of arterial hypertension with angiotensin converting enzyme (ACE) inhibitors has been shown to be effective with a low incidence of adverse effects compared with other drug classes. Furthermore, treatment with ACE inhibitors may slow the progression of renal function impairment in certain groups of patients, such as those with diabetes. Most ACE inhibitors are prodrugs which are converted by hepatic esterolysis to an active diacid metabolite. Only captopril and lisinopril have sufficient oral bioavailability and are given as active drugs. ACE inhibitors can be subdivided into 3 classes with regard to the active group: the majority of ACE inhibitors are carboxyl-containing drugs, a new class of ACE inhibitors possess a phosphoryl-group and captopril and related compounds are sulfhydryl-containing drugs. The predominant elimination pathway of ACE inhibitors is excretion via the kidneys. Therefore, renal insufficiency is associated with reduced elimination of most ACE inhibitors and, thus, altered pharmacokinetic properties. This is most evident in chronic renal failure when glomerular filtration rates (GFR) are < 30 to 40 ml/min (1.8 to 2.4 L/h). As renal clearance decreases, the peak plasma concentration and area under the plasma concentration-time curve of the active drugs or diacids are increased and time to peak concentrations and half-life are prolonged. However, there are large between-drug differences in the changes in pharmacokinetic parameters, resulting in different degrees of drug accumulation after consecutive administration. This leads, for example, to high accumulation rates for drugs such as lisinopril, or cilazaprilat. In contrast, fosinopril, which is also excreted to a large extent by the hepatobiliary pathway, does not seem to accumulate in renal failure. In general, pharmacokinetics and conversion of prodrugs seem to be slightly affected in chronic renal failure; however, these changes do not appear to be clinically relevant. Efficiency of clearance for prodrugs or active drugs and their respective metabolites by haemodialysis or peritoneal dialysis varies considerably. For some ACE inhibitors, such as captopril or enalapril, the high elimination fraction by haemodialysis necessitates a supplemental dose after dialysis. Other ACE inhibitors, such as quinapril or cilazapril, are only poorly eliminated by haemodialysis or peritoneal dialysis. Dosage recommendations for treatment with ACE inhibitors in chronic renal failure depend on the specific pharmacokinetic properties of the various agents. For most ACE inhibitors, dosage adjustment is recommended in moderate and severe impairment of renal function, with resultant dosages being 25 to 50% of those recommended for patients with normal renal function. PMID- 8462232 TI - Cadaver renal transplantation in children. Incidence, immunosuppression, outcome, and risk factors. AB - In North America, about 50% of all renal transplants done in children are from a living-related donor source--a figure two and a half times greater than the comparative figure for Europe. Graft survival in children is lower for cadaveric donor (CD) than for living-related donor (LRD) kidneys. Four of 10 children with a CD kidney lose their graft within four years. Since it is unlikely that the availability of LRD kidneys will increase, attention must be focused on improving outcome of cadaver renal transplants in children. This review analyzes factors that affect graft outcome. Young recipient age, utilization of kidneys from very young donors, and cold ischemia time are detrimental to prolonged graft survival. Additional factors that impact adversely on cadaver graft survival are a history of previous transplantation, absence of a DR match, and black ethnic origin of the recipient. An understanding of risk factors to graft survival should enable physicians to optimize cadaver renal transplantation in children. PMID- 8462233 TI - Difficult parents. From adversaries to partners. AB - The pediatrician's job becomes frustrating when it is necessary to deal with difficult parents. Some physicians may not have the training or inclination to engage such parents in a therapeutic partnership. This paper discusses tools available to physicians which will help them develop an effective partnership that includes uncovering the hidden meaning behind a child's illness; understanding the reciprocal nature of partnerships; and the importance of determining each party's goals, roles, and expectations. Negotiating these steps enables physicians to develop a productive relationship with difficult parents of sick children. This strategy can facilitate the child's medical care and improve the parents' and physician's satisfaction with the services rendered. This paper also discusses steps to take when these attempts are not sufficient to handle the situation. PMID- 8462234 TI - Exercise-induced bronchospasm in nonasthmatic obese children. AB - The frequency, degree, and pattern of bronchial reactivity to exercise were compared in 13 obese and 14 control children, ages 6 to 10 years, with no history of asthma. Spirometry was performed before and every three minutes after a seven minute exercise challenge on a treadmill. There were 11 obese children and 6 controls who had at least a 15% fall in at least one of three monitored pulmonary function parameters (P < .05). The group mean percentage falls in FEV1 and FEF25% 75% were significantly greater in the obese group than in the controls. The pattern of bronchospasm, occurring soon after the exercise challenge, is consistent with that found in the known asthmatic population. A significant correlation was found between triceps skin-fold thickness and degree of fall in FEF25%-75% (r = .55, P < .005). This study demonstrated that significantly greater frequency and degree of bronchospasm of the smaller airways occur in obese children, partially related to the amount of subcutaneous fat. Whether exercise-induced bronchospasm leads to exercise avoidance and obesity or whether obesity causes or enhances bronchial hyperreactivity to exercise requires further study. PMID- 8462235 TI - A survey of Quebec pediatricians' attitudes toward donor insemination. AB - Inspired by a study done in France, Quebec pediatricians were surveyed regarding their knowledge of children conceived by donor insemination (DI) and their families, as well as their attitudes and opinions about DI. A two-part questionnaire was mailed to all 487 members of the Quebec Association of Pediatricians. One hundred and ninety-seven (40%) responded. Findings indicate that Quebec pediatricians have treated few children conceived by DI and know little about how their families are handling the issue of DI. Most pediatricians favored telling DI offspring about their mode of conception, and almost half stated that such children, at maturity, should have the right to know their biological fathers. Their opinions reflect the growing trend toward openness in adoption and DI. PMID- 8462237 TI - Childhood masturbation. PMID- 8462236 TI - High-dose urokinase therapy in newborn infants with major vessel thrombosis. AB - The effectiveness of urokinase therapy for thrombosis in children, particularly in newborn infants, has not been established. We report our experience with the local administration of high-dose intrathrombus urokinase in two newborn infants. One infant had aortic thrombosis and the other, thrombosis of the right femoral artery. The known abnormalities in the newborn's fibrinolytic mechanism provide the rational basis for the therapeutic use of high doses of plasminogen activators. No significant abnormalities of our patients' fibrinolytic systems were found, and effective thrombolysis was achieved. A literature review of the use of urokinase therapy for thrombosis in children reveals great disparities in dosage and outcome. We believe that fixed-dose regimens should be replaced by individually adjusted thrombolytic therapy and that the need for higher doses of urokinase in newborns should be studied further. PMID- 8462238 TI - Computed tomography in diagnosing retropharyngeal abscess in children. PMID- 8462239 TI - The role of the male caretaker in Munchausen syndrome by proxy. PMID- 8462240 TI - Discordant monozygotic twins with markedly different grades of anterior lens capsule vascularity. PMID- 8462241 TI - Child abuse by poisoning. Why is alprazolam difficult to detect? PMID- 8462242 TI - Reflections of a grandparent. PMID- 8462244 TI - Evaluation and management of solitary and multiple pulmonary nodules. AB - Solitary pulmonary nodules are malignant in 50% of cases. The 5-year cure rate after resection of a malignant nodule averages 50% and is even higher if the nodule is small. Stability for 2 years suggests benignity, and the presence of calcification in certain patterns indicates that the nodule is probably benign. Biopsy of the nodule may establish benignity. The "wait and watch" strategy may be advisable under certain circumstances. Multiple pulmonary nodules are usually due to metastatic spread from an extrapulmonary primary tumor. Biopsy is usually advisable because the nodules may be due to a curable benign process. PMID- 8462243 TI - Epidemiology and etiology of lung cancer. AB - Lung cancer incidence and mortality have increased sharply during this century, making it a common cause of death and the most frequent fatal cancer in men and women. The known behavioral and environmental causes--cigarette smoking, asbestos and other occupational carcinogens, radon, and environmental tobacco smoke--are responsible for the majority of cases. Although the proportion of adults who smoke in the United States has dropped since the mid-1960s, the incidence of lung cancer in the United States is expected to continue to rise through the 1990s because of the long latency between initiation of smoking and the occurrence of the disease. Efforts to alter lung cancer mortality by early detection and better therapy have not yet succeeded in reversing this trend. The modification of risk factors is currently the most effective approach to reducing future lung cancer deaths. PMID- 8462245 TI - Role of phototherapy, laser therapy, brachytherapy, and prosthetic stents in the management of lung cancer. PMID- 8462246 TI - Oncogenes and growth factors in human lung cancer. AB - We are only beginning to understand the importance of lung cancer tumor biology in relation to prognosis and response to therapy. Many of the biologic and genetic changes we have described are preliminary observations and require further confirmation before clinical use. However, information concerning three oncogenes may soon prove to be helpful in the clinical arena: the myc genes in SCLC, and the ras genes and c-erbB-2 in NSCLC. In general their presence identifies poor patient response to therapy and poor survival. These markers are currently being used in a clinical setting at some research centers, but are not recommended for general diagnostic or prognostic use without further confirmation of their utility. Incorporation of this information with that learned by standard staging procedures may result in improved understanding of patient prognosis and challenge current concepts of lung cancer treatment. For example, surgically resected stage I NSCLC patients may benefit from adjuvant therapy if found to have these adverse biologic factors, and require more stringent follow-up after therapy. Finally the understanding of the pathogenesis of lung cancer may enable the development of novel therapy directed against these growth pathways. Our ultimate goal is to derive a therapeutic and prognostic paradigm involving both molecular-genetic and clinical factors to arrive at an optimal staging model and treatment plan. PMID- 8462247 TI - Lung cancer staging classification. AB - In presenting the staging system, I recognize that in a given patient the total tumor burden cannot be precisely quantitated, and the balance between host defenses and the heterogeneity of the malignancy is not measurable. These and other complex interacting biological variables will influence the subsequent course of the disease. However, our data support the premise that the straightforward indices of disease extent in the TNM system permit a simple yet valid classification that best reflects prognosis. Patients can be grouped together according to certain measurable common features of their disease so that within each stage group treatment options and survival expectations will be generally similar. In this manner reliable and valid comparisons of the results of different modalities of therapy can be made. Survival data according to staging criteria are a measure of the efficacy of available therapy for lung cancer; thus, the staging information serves as a valuable guide for treatment planning. PMID- 8462248 TI - Radiologic manifestations of bronchogenic cancer. AB - Radiologic imaging provides crucial information about bronchogenic cancer and is complementary to more invasive diagnostic techniques. The diagnosis is often suspected initially from the chest radiograph. The CT scan permits the most complete analysis of the extent of the tumor, nodal metastasis, and distant metastasis and serves as a guide to further evaluation and surgery. MRI, at the current stage of development, is generally reserved for cases in which CT findings are inconclusive. Rapid technologic advances have the potential for altering this imaging hierarchy in the near future. PMID- 8462249 TI - Sputum cytology. AB - Examination of sputum is the least invasive method of obtaining a cytologic diagnosis in a patient suspected of harboring lung cancer. Cytologic diagnosis has advanced to a point where it is of comparable value to histology. The authors discuss the sensitivity, specificity, reliability, and pitfalls of sputum cytology as well as the role it plays in screening of early lung cancer. The advantages and shortcomings of sampling and cytopreparatory techniques are also reviewed. Concluding remarks outline future developments in sputum cytology. PMID- 8462250 TI - The role of bronchoscopy in lung cancer. AB - Flexible fiberoptic bronchoscopy is the most useful invasive technique for diagnosing lung cancer. This article details the use and efficacy of bronchoscopy with such established techniques as forceps biopsy, brush biopsy, and bronchial washing in the diagnosis and staging of bronchoscopically visible central lung cancer and peripheral lung cancer. The efficacy of such newer techniques as transbronchial needle aspiration, transbronchial curettage, ultrathin fiberoptic bronchoscopy, and quantitation of tumor markers in bronchoalveolar lavage fluid is also discussed, along with the complications of bronchoscopy and new techniques for detecting early lung cancer. PMID- 8462251 TI - The role of transthoracic needle biopsy for the diagnosis and staging of lung cancer. AB - Percutaneous transthoracic needle biopsy (TNB) is a simple and safe procedure with high diagnostic accuracy for the diagnosis and staging of cancer in the lung, hilum, and mediastinum. The complication rate is low and consists primarily of pneumothorax, with only a small percentage of these requiring chest tube reexpansion. Major complications are rare. Computed tomographically guided biopsy is a powerful adjunct to fluoroscopic biopsy and expands the application of TNB to include most thoracic lesions. TNB is the initial diagnostic procedure of choice in peripheral lung lesions, suspected focal metastases, and most hilar and mediastinal masses. Its proper role in the diagnosis and staging of lung cancer requires the close collaboration of the radiologist, cytopathologist, and the patient's primary physician. PMID- 8462252 TI - Basics of renal anatomy and physiology. AB - A kidney contains over 1 million functioning units called nephrons. Each nephron is composed of a glomerulus and tubule. The glomerulus acts to filter the blood free of cells and large proteins, producing an ultrafiltrate composed of the other smaller circulating elements. The ultrafiltrate enters the tubule, which is highly specialized at various segments, to produce the final urine by removing substances from the tubular fluid (reabsorption) or adding substances to the tubular fluid (secretion). Filtration, reabsorption, and secretion keep the organism in balance in terms of water, minerals, electrolytes, and hydrogen ion concentration and eliminate the toxic substances produced by the body. The major known hormonal functions of the kidney influence blood pressure, calcium metabolism, and red blood cell production. PMID- 8462253 TI - Fundamentals of clinical acid-base evaluation. AB - The final diagnosis of acid-base perturbations relies on laboratory analyses. The major direct tools of assessment are arterial pH and PCO2 and serum electrolytes. From these values, a diagnosis of metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis with or without an excess anionic gap and with or without a proper compensatory response is made. PMID- 8462254 TI - Laboratory evaluation of renal tubular acidosis. AB - In this article, the renal tubular acidoses are briefly described, individual laboratory tests of urinary acidification are reviewed, and the administration and interpretation of these tests are discussed. A systematic approach to the laboratory evaluation of hyperchloremic metabolic acidosis is included. PMID- 8462255 TI - Urinalysis and urinary sediment in patients with renal disease. AB - Examination of the urine plays a vital role in the diagnosis of kidney diseases. Proteinuria is an important indicator of renal disease and the types of proteins found in the urine help distinguish glomerular and tubular disorders. The findings of casts and blood cells in the urine provide valuable clues about the causes of the underlying renal pathology. Crystals may be found in the urine of healthy individuals and in patients with urolithiasis, toxic damage, and chronic renal failure. PMID- 8462256 TI - Evaluation of renal concentrating and diluting ability. AB - Evaluating the diluting and concentrating capacity of the kidney can be accomplished with three basic laboratory tests, urine and plasma osmolalities, and circulating levels of antidiuretic hormone. When used with simple techniques to stimulate dilution and concentration, these tests will provide critical clinical information in patients with defects in either dilution or concentration of the urine. PMID- 8462257 TI - Perturbations in sodium balance. Hyponatremia and hypernatremia. AB - Perturbations of serum sodium concentration are the most common electrolyte abnormalities seen in clinical medicine. Patients may exhibit profound alterations in mental status or be asymptomatic. Appropriate diagnosis and treatment is essential to reducing morbidity from serum sodium abnormalities. This article reviews the etiology, symptoms, and treatment of hyponatremic and hypernatremic syndromes. PMID- 8462258 TI - Perturbations in potassium balance. AB - Hyperkalemia and hypokalemia are commonly encountered in medical practice. Differential diagnosis and therapeutic approaches have been presented to provide an informed choice for the practicing physician. PMID- 8462259 TI - Assessment of hypocalcemia and hypercalcemia. AB - Methodologic aspects including causes of factitious hypocalcemia and hypercalcemia are summarized. The differential diagnosis of hypocalcemia is reviewed under three main headings: hypoalbuminemia, hypocalcemia with decreased parathyroid hormone (PTH) action or activity, and hypocalcemia with normal PTH action and activity. The differential diagnosis of hypercalcemia is subdivided into three broad categories: hyperproteinemia, PTH-mediated hypercalcemia, and non-PTH-mediated hypercalcemia. The causes of hypocalcemia and hypercalcemia are outlined with a focus on pathophysiology and clinicochemical sequelae. A laboratory perspective is emphasized in outlining management strategies. PMID- 8462260 TI - Assessment of hyperphosphatemia and hypophosphatemia. AB - Methodologic aspects including causes of factitious hyperphosphatemia and hypophosphatemia are summarized. The differential diagnosis of hyperphosphatemia is reviewed under its three broad causes: decreased glomerular filtration rate, increased exogenous or endogenous phosphate load, and increased renal tubular phosphate reabsorption. The differential diagnosis of hypophosphatemia is reviewed under its three broad causes: inadequate gastrointestinal input, excess phosphate losses, and transcellular shifts. The consequences of hyperphosphatemia and hypophosphatemia are outlined with a focus on pathophysiologic and clinicochemical sequelae. A laboratory perspective is emphasized in outlining management strategies. PMID- 8462261 TI - Laboratory evaluation of magnesium status. Renal function and free intracellular magnesium concentration. AB - In summary, magnesium plays an essential role in both extracellular and intracellular metabolism. Even though biologists recognize the importance of magnesium, clinicians often are unaware of the frequency and significance of magnesium disturbances. Some clinicians recommend routine measurement of magnesium when other electrolyte analyses are required for the care of patients. Others have reported a high frequency of hypomagnesemia in hospitalized patients, but the clinical significance of this observation was not evident. Patients with coexisting hypokalemia of any cause require particular attention however, and it is important to assess magnesium status in that setting. The assessment of magnesium status is difficult because of the distribution of magnesium within the intracellular compartment. The majority of body magnesium is located within soft and hard tissues and most intracellular magnesium is complexed and not available for measurement. Accordingly, no single determination is available to accurately assess magnesium status. The simplest and most useful approach is the determination of serum magnesium and renal magnesium clearance and interpretation of these parameters in light of complete history and clinical evaluation of the patient. Accordingly, one combines the laboratory assessment with the clinical evaluation. Other tests, such as determination of serum and intracellular free Mg2+ activity by either fluorescent or 31P-NMR techniques, are not particularly useful in the routine laboratory. These approaches currently are being used on an experimental basis to assess the role of magnesium in health and disease, which may lead to better indices of clinical evaluation in the future. PMID- 8462262 TI - Proteinuria. AB - Proteinuria is an important finding in patients because it may signify either a benign disorder or renal disease. A systematic approach to evaluation, which incorporates a careful clinical evaluation coupled with a few simple laboratory tests, is required to determine whether the patient can be followed, or whether a more invasive study, such as renal biopsy, is indicated. Although the causes of proteinuria are diverse, a structured approach to the patient with proteinuria provides maximal information with minimal expense and risk. PMID- 8462263 TI - Laboratory investigation of renal stone disease. AB - Renal stone disease is a chronic disease associated with a high rate of recurrences and hospitalizations. Over the past three decades, the incidence of nephrolithiasis has increased by 60% to 75%. Because there is a significant amount of morbidity associated with development of stone disease, a comprehensive yet simple evaluation to determine the cause of the problem is warranted. PMID- 8462264 TI - Important aspects concerning evaluation of renal function and blood pressure. Kinins, prostaglandins, lead. AB - The kallikrein-kinin and prostaglandin-thromboxane-leukotriene systems and the body lead burden all influence renal function and systemic blood pressure to some extent. Because these systems may become generally accepted as more important in assessing renal function and blood pressure in the future, a brief overview of each has been given. PMID- 8462265 TI - Assessment of renal function in the young. Special considerations. AB - Infants are born in a state of renal insufficiency and have varying degrees of maturity of tubular processes. This is even more striking in premature infants. This article presents a review of glomerular and tubular function assessment with particular attention to factors that impact these developmental and maturational factors. PMID- 8462266 TI - Assessment of renal function in the old. Special considerations. AB - The most important clinical renal function to monitor with age is glomerular filtration rate (GFR), as all other changes in renal function tend to parallel changes in GFR. The serum creatinine and creatinine clearance have become the clinical tests most frequently used to measure GFR. The creatinine clearance decreases at a rate approximately 1% per year after age 40 years. Mean serum creatinine values, however, fail to increase with age because creatinine production, which is dependent on muscle mass, falls at nearly the same rate as the renal clearance of creatinine. Serum creatinine concentrations must be interpreted with this in mind when used to determine or modify dosages of drugs cleared totally, for example, the aminoglycoside antibiotics, or partially, for example, digoxin, by the kidney. PMID- 8462267 TI - Evaluation of elevated blood pressure. AB - The clinical laboratory is essential to the successful and complete evaluation of the patient with hypertension. A reasonably thorough knowledge of the important physiologic components of blood pressure regulation, in conjunction with a good history and physical examination and a simple panel of screening tests serve to detect or rule out the presence of secondary forms of hypertension in the majority of patients. PMID- 8462268 TI - Assessment of renal function--glomerular and tubular. AB - The tests most commonly used to estimate the status of renal function via alterations in glomerular filtration rate (GFR) are plasma creatinine concentration (PCr), blood, urea, nitrogen (BUN), and creatinine clearance (CCr). Unfortunately, these tests have some drawbacks. Nevertheless, they are quite useful to clinicians aware of their limitations, especially in many instances when it may be unnecessary or impractical to have precise measurements. Accordingly, serial measurements of PCr, especially when related to simultaneous BUN determinations, or CCr, may suffice. However, the functional status of the kidneys often needs to be corroborated by more precise methods when subtle changes in renal function are detected or when clinically indicated. PMID- 8462269 TI - Quantitation of renal function using radioisotopic techniques. AB - Radioisotopic methods are practical for clinical use because they do not require continuous intravenous infusion or urine collection. This obviously is of great advantage in infants and small children, in whom accurate urine collection is difficult, but the techniques apply to adults as well. The ability to determine individual kidney function is a major benefit. Accuracies of the radioisotopic techniques vary but generally are within clinically acceptable ranges. The need for accuracy and reproducibility can be balanced with the desire for speed and convenience when choosing among the different techniques. Methods that use plasma sampling provide greater accuracy and are recommended in cases of severe dysfunction, whereas methods such as Gates' camera method, which eliminates plasma samples, can be completed in minutes. Radioisotopic techniques are most useful in the ranges of mild to moderately decreased function, in which serum creatinine concentration is nondiagnostic, and although they are much less accurate at markedly low renal function levels, so is 24-hour creatinine clearance. In conclusion, radiopharmaceutical agents offer a wide array of possible techniques for simple, accurate, and noninvasive measurement of global as well as individual GFR and ERPF. PMID- 8462270 TI - Serologic evaluation of renal status. AB - Mechanisms of immunologic injury causing glomerulonephritis are based on immune complex or autoantibody deposition with activation of complement. Circulating immune complex disease can be diagnosed and monitored with improved assays for immune complexes, DNA antibodies, complement levels, and complement activation products. Etiologic auto-antibodies for the Goodpasture antigen, neutrophil enzymes, and ones directly promoting complement activation are now quantitated for more accurate serologic diagnosis. The spectrum of postinfectious glomerulonephritis also presents several new measurements for assessing clinical status. Diagnosis and monitoring of glomerulonephritis now entails panel testing for these humoral abnormalities that are useful to establish the etiology and treatment regimens. PMID- 8462271 TI - Diagnosis of acute and chronic renal failure. AB - This article presents a systematic approach--through history, physical examination, and laboratory findings--for the pursuit of the diagnosis of acute and chronic renal failure. These guidelines are based on the pathophysiology of the syndromes. In management, they serve the goal of staying the failure and regaining renal function. PMID- 8462272 TI - An on-line method in studying music parsing. AB - Listening to music entails the construction of a mental representation based on partial and ambiguous information. This study examines an experimental method that reflects such parsing decisions on-line by detecting the cognitive load resulting from temporary parsing failures. The method investigated was a divided attention paradigm in which listening to music was the primary task and click detection was a concurrent secondary task. It was hypothesized that increasing the complexity of the primary task by introducing an unprepared chromatic modulation results in an increase in response latencies to a click presented immediately after the modulatory shift. The support of this prediction by musicians' data provides evidence for the sensitivity of the paradigm. The failure of non-musicians to reflect the expected load is attributed to their attention-allocation strategy. These results are discussed in terms of their implications on the view of the musical parser as deterministic. PMID- 8462273 TI - Frames of reference in vision and language: where is above? AB - Spatial terms such as "above" must be used and interpreted with respect to some frame of reference. Perceptual cues for verticality were varied in four experiments to investigate whether the comprehension and production of "above" is based on a viewer-centered (deictic) frame, an environment-centered (extrinsic) frame, or an object-centered (intrinsic) frame of reference. "Above" was usually interpreted with respect to an environment-centered reference frame, but there was a significant contribution from object-centered reference frames as well; the viewer-centered reference frame made no independent contribution to "above". The meaning of "above" appears not to specify a particular reference frame; rather, selection of a reference frame during spatial assignment determines how spatial terms such as "above" and "below" will be used and interpreted. PMID- 8462274 TI - A perceptually-based model of children's earliest productions. AB - A model is proposed to account for processes underlying the initial extraction and representation of words. The model incorporates perceptual salience into a framework provided by autosegmental phonology. In one study, predictions of the model were tested in a corpus of utterances obtained from three children in the one-word speech period. Analyses of the corpus supported the predictions, suggesting that salience of elements such as stressed and final syllables may contribute to the form of early productions and, specifically, to the form of utterances containing filler syllables and full or partial reduplications. Because the data for this study were children's productions, and the model concerns children's representations, a second study was carried out to investigate representations somewhat more directly. That study also explored the possible influence of an additional prosodic factor on the form of early words. A word-learning task with 2-year-olds, 3-year-olds and adults assessed whether children would attend to stress pattern or segmental sequence in identifying the referent for a word. As expected, children did rely on prosody in their word choices far more frequently than did adults, suggesting that one prosodic component, stress pattern, may in some cases be prominent in a child's representation for a word. The results of the two studies provide support for the utility of the autosegmental framework, as well as additional evidence for the perceptual salience of stressed and final syllables and of stress pattern. PMID- 8462275 TI - Variations in genome mass. AB - 1. Genome size varies considerably among vertebrates, ranging from less than 1 pg to more than 200 pg; the amount of DNA differing among individuals in a population can equal the amount in the entire structural gene complement. 2. Recent technological advances permit evaluation of genome size variation at several levels including sub-chromosomal, chromosomal and cellular. 3. Genome size variation may also be viewed from taxonomic levels, and across evolutionary time frames. 4. As sources of genome size variation are identified and studied, the conundrum of the C-value paradox (lack of correlations among genome size, genomic complexity and phylogenetic status of organisms) may prove to be more apparent than real. 5. For example, the limited and relatively constant genome size of avians may be related to the physiological constraints of flight. PMID- 8462276 TI - DNA fingerprinting of the roe deer, Capreolus capreolus L. AB - 1. After digestion of roe deer DNA with the restriction enzyme HaeIII, microsatellite sequences cross-hybridize with the digoxigenin-labeled multilocus probe (GTG)5 yielding non-radioactive DNA fingerprints. 2. Since different organs of the same individual exhibit identical fingerprints, somatic stability is confirmed. 3. The method discloses a high potential of individualization. The probability that two unrelated roe deer have identical fingerprints was found to be 10(-7). 4. It is shown that band-similarity indices can be used to estimate the degree of relationship within groups of individuals. PMID- 8462277 TI - Isolation of Antho-RFamide related peptides from the eyestalks of blue crab. AB - 1. Two carboxyl-terminally amidated peptides (CP1 and CP2) were isolated from the blue crab (Callinectes sapidus) eyestalks by a method of carboxyl-terminal analysis. 2. The peptides were sequenced as pGlu-Gly-Arg-Phe-amide (CP1) and pGlu Leu-Gly-Arg-Phe-amide (CP2). 3. Each carboxyl-terminus of the peptides was precisely determined by amino acid analysis utilizing phenylisothiocyanate derivatives. 4. CP1 was identical to the sea anemone neuropeptide, Antho-RFamide. PMID- 8462278 TI - Fatty acid-binding protein in bovine longissimus dorsi muscle. AB - Experiments were conducted to purify and obtain amino acid sequence data for fatty acid-binding protein from bovine longissimus dorsi muscle. 1. Separation of sarcoplasmic proteins by fractionation on Sephadex and DEAE cellulose columns indicated that a low abundance fatty acid-binding protein exists in bovine l. dorsi muscle. 2. Fatty acid-binding protein in bovine l. dorsi muscle cannot be separated from myoglobin by standard protein purification procedures. However, partial sequencing of a partially purified protein fraction indicated the presence of an NH2-terminally blocked protein. 3. Myoglobin bound palmitate under the in vitro conditions of these experiments. PMID- 8462279 TI - Purification and characterization of metallothionein and its activation of pyridoxal phosphokinase in trout (Salmo gairdneri) brain. AB - 1. Brain metallothionein was isolated and purified for the first time from rainbow trout. 2. Brain metallothionein exhibited an elution volume (Ve/Vo) of 2.0, had a molecular weight of 6762 Daltons, and contained a zinc content of 9 micrograms/mg protein. 3. Brain pyridoxal phosphokinase was isolated and assayed for the first time in rainbow trout. 4. Zinc (0.20 microM) or zinc metallothionein (6-30 microM) stimulated the activity of brain pyridoxal kinase in a linear fashion. 5. The results of these studies are interpreted to suggest that in trout brain zinc metallothionein may participate in metabolism of vitamin B6 and formation of pyridoxal phosphate, the active coenzyme. PMID- 8462280 TI - Inhibition of human and murine cytosolic epoxide hydrolase by group-selective reagents. AB - 1. Human and murine cytosolic epoxide hydrolase were inhibited by thiol-, imidazole- and carboxyl-selective reagents. They were not inhibited by amino-, guanido- or activated serine-selective reagents. 2. Murine, but not human, cytosolic epoxide hydrolase was inhibited by N-bromosuccinimide, a tryptophan selective reagent. 3. Based on sequence data from peptides isolated from CNBr digests, human and murine CEH share areas of sequence homology. Of the five unique human CEH CNBr peptides sequenced, three shared common sequences with one of the unique murine CEH CNBr peptides. The human and murine CEH peptides with common sequences had between 64 and 78% sequence identity. 4. A cysteine important for the activity of murine CEH appears not to be in the active site as judged by N-phenylmaleimide inhibition in the presence and absence of either (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)glycidol, a competitive inhibitor, or trans stilbene oxide, a substrate. PMID- 8462281 TI - Inhibition of epoxide hydrolase from human, monkey, bovine, rabbit and murine liver by trans-3-phenylglycidols. AB - 1. trans-3-Phenylglycidols were potent inhibitors of cytosolic epoxide hydrolases in all species tested. 2. The order of inhibitor potency varied from species to species but trans-3-(4-nitrophenyl)glycidols were always the most potent inhibitors tested for cytosolic epoxide hydrolase. 3. The S,S-enantiomer was a more potent cytosolic epoxide hydrolase inhibitor than the R,R-enantiomer when a free hydroxyl group was present. However, (2R,3R)-1-benzoyloxy-2,3-epoxy-3-(4 nitrophenyl)propane was always a better inhibitor than the (2S,3S)-enantiomer. 4. All microsomal epoxide hydrolases were poorly inhibited by the trans-3 phenylglycidols, and related compounds, tested. The best new microsomal epoxide hydrolase inhibitor tested was (1S,2S)-1-phenylpropylene oxide which gave 18-63% inhibition, at 2 mM, depending on the species tested. PMID- 8462282 TI - Comparison of the mucus glycoproteins present in the different layers of rat gastric mucosa. AB - 1. Applying a newly developed separation method, mucus glycoproteins (mucins) present in the different layers of gastric mucosa in rats were studied. 2. Distributions of mucin in the four layers of gastric mucosa expressed as mg mucin hexose per animal are: deep mucosa of corpus, 705; deep mucosa of antrum, 163; surface mucus, 421; mucus gel, 30; and soluble mucus, 173. 3. Relatively low molecular sugar chains, having a small amount of neutral sugars, are rich in the deep corpus and deep antral mucin. 4. Higher molecular size carbohydrate chains, rich in fucose and galactose, are abundant in the surface mucus and mucus gel derived mucin. PMID- 8462283 TI - Glycogen hyperaccumulation in white muscle fibres of RN- carrier pigs. A biochemical and ultrastructural study. AB - 1. The dominant RN- gene affects meat quality of pigs by increasing the glycogen content of muscle. Glycogen localization was studied in Longissimus dorsi muscle from RN- carrier pigs (RN- pigs) and rn+ rn+ homozygous pigs (rn+ pigs). 2. Ultrastructural study showed an excess of glycogen in the sarcoplasm of white fibres from RN- pigs as compared to rn+ pigs. 3. Lysosome-enriched fractions extracted from muscles contained 6% of the tissue glycogen content in both types of pigs. The distribution of the glycogen particles between sarcoplasm and lysosomes appeared to be similar in both RN- and rn+ pig tissues. 4. White fibres from RN- pigs with an increased glycogen level showed two ultrastructural alterations: the sarcoplasmic compartment was abnormally enlarged and a large proportion of mitochondria was morphologically modified. 5. The RN- gene seems, therefore, to be associated with alterations in the glycolytic metabolism, in the distribution of proteic compartments and in the oxidative metabolism of white muscle fibres. PMID- 8462284 TI - Insulin induction of c-Ki-ras in rat liver and in cultured normal rat hepatocytes. AB - 1. Insulin administration in neonatal rats causes a dramatic accumulation of the major c-Ki-ras transcript. 2. The level of c-Ki-ras transcript is greatly reduced in alloxan-induced diabetic rats. 3. Injection of insulin in alloxan-induced diabetic rats is able to restore almost completely the level of c-Ki-ras transcript found in insulin-induced normal rats. 4. Results from nuclear run-off experiments reveal that the inductive effect of insulin is at the level of transcription of the c-Ki-ras gene. 5. As in whole animals, insulin is also able to induce the expression of c-Ki-ras in cultured normal hepatocytes. 6. This inductive effect of insulin is markedly reduced in hepatocytes which have been previously treated with the tumour promoter, 12-O-tetradecanoylphorbol-13 acetate for 24 hr, a result suggesting that at least part of the effect of insulin is mediated via protein kinase C. PMID- 8462285 TI - Comparative studies of synthesis, phosphorylation, DNA binding and proteolytic characteristics of a novel protein during phases of the mouse spleen cell cycle. AB - 1. Cultured mouse spleen cells were exposed to the mitogen Concanavalin A followed by isoproterenol, and nuclei were electronically sorted from seven partitions of the cell cycle. 2. Several nuclear proteins, including stress proteins, which were cell-cycle-stage specific, were elicited by isoproterenol as determined by micro-electrophoresis and fluorography. 3. Two novel S-phase proteins (X0 and X') demonstrated differing synthesis and phosphorylation patterns during the cell-cycle phases. 4. X' showed DNA binding characteristics and proteolytic properties (hydrolyzing X0 or beta-galactosidase); both proteins were cell-cycle regulated. PMID- 8462286 TI - An arm immersion model of compromised skin (II). Influence on minimal eliciting patch test concentrations of nickel. AB - The transition metal nickel is a very common cause of allergic contact dermatitis (ACD). In the general population, adults with hand eczema have a high incidence of allergy to nickel, and nickel allergy is high in occupational dermatoses and is often linked to wet work. Nickel may be found as a trace contaminant in some consumer products, e.g., household cleaning agents. It has therefore been debated whether these levels, whilst not a primary cause, might be sufficient to maintain ACD. The minimal concentration of nickel in patch tests on normal skin that will elicit an allergic reaction in highly sensitised subjects is 1-10 ppm. This trial assessed whether reactivity to nickel was altered on compromised dorsal forearm skin and compared this to normal skin on the contralateral dorsal forearm and on the back. Skin damage consequent upon arm immersion in sodium dodecyl sulphate (SDS) greatly enhanced reactivity to nickel on the forearm, with the dorsal aspect reacting most both in number of reactions at each concentration and in the minimal eliciting concentration, which was 0.5 ppm in 2/20 under the conditions of a 48 h occluded patch. PMID- 8462287 TI - Contact dermatitis from dielectric fluids in electrodischarge machining. AB - We report an outbreak of irritant contact dermatitis in the aerospace industry from electrodischarge machining (EDM). 20 workers doing EDM developed irritant contact dermatitis from the dielectric fluid used in EDM, a form of precision metal machining that is widely used in mould making and precision engineering. Dielectric fluid contains hydrocarbons that are aromatic, paraffinic or naphthenic and are skin irritants. Irritant contact dermatitis from dielectric fluid has not been reported previously. EDM will become more widespread and occupational dermatitis from dielectric fluid is likely to become more prevalent in the future. Our experience was that irritant contact dermatitis from dielectric fluid can be prevented by simple preventive measures such as personal hygiene and health education. PMID- 8462288 TI - Frequency of false-negative reactions to the fragrance mix. AB - To estimate the frequency of false-negative reactions to the fragrance mix, the 8 constituents of the mix in concentrations of 5% (2% for cinnamic aldehyde) were added to the European standard series for routine testing. Patients with positive reactions to individual ingredients in the absence of a reaction to the mix were retested with serial dilutions. In a 4-month period, 677 patients were tested. 61 (9%) reacted to the mix and to 1 or more of the ingredients. 4 patients (0.6% of all patients tested and 6.2% of the patients allergic to fragrances) had false negative reactions to the mix. They were allergic to cinnamic alcohol, geraniol, isoeugenol and oak moss (1 reaction each), in the absence of a reaction to the fragrance mix. It is concluded that the currently used concentration of the mix (8 x 1%) not infrequently results in false-negative reactions, and that further research should be done to overcome this problem. PMID- 8462289 TI - Measurement of skin-fold thickness in the guinea pig. Assessment of edema inducing capacity of cutting fluids, acids, alkalis, formalin and dimethyl sulfoxide. AB - The rabbit has been used for decades for predictive testing of skin irritancy, but in recent years, the guinea pig has been suggested as an alternative, especially for assessment of one of the components of the irritant reaction: edema (fluid accumulation). A method based on skin-fold measurements with Harpenden calipers has been developed and modified. In previous papers, experience with sodium lauryl sulphate, nonanoic acid and industrial solvents was reported. The present results concern the use of cutting fluids, buffered and unbuffered acid and alkaline solutions, formalin and dimethyl sulfoxide. This inexpensive and comparatively unsophisticated method afforded clear dose-response relationships and good discriminating power. The only exception was the acid and alkaline solutions, where no changes in skin-fold thickness were observed despite their documented irritant potential. The appearance of erythema (visual scoring) and the increase in skin-fold thickness, and their relationship, are discussed with some illustrative examples. The method described is now well standardized and is suited for predictive testing of the edema-inducing capacity of chemicals and products. PMID- 8462290 TI - Allergic contact dermatitis of the lip margins from para-tertiary-butylphenol in a lip liner. AB - We describe the use of gas chromatography with mass spectrometry (GC-MS) in the investigation of a case of allergic contact dermatitis of the lip margins caused by a lip liner. Patch testing identified sensitization to para-tertiary butylphenol-formaldehyde resin (PTBP-FR), a resin glue frequently used in leather work but rarely found in cosmetics. Investigation specified the para-tertiary butylphenol (PTBP) component of the resin as the hapten responsible for the allergic contact dermatitis, as well as for associated depigmentation. PMID- 8462291 TI - The sensitizing potency of Euxyl K 400 and its components 1,2-dibromo-2,4 dicyanobutane and 2-phenoxyethanol. AB - Using a modified FCA (Freund's complete adjuvant) procedure, the sensitizing capacity of Euxyl K 400 and its ingredients, 1,2-dibromo-2,4-dicyanobutane and 2 phenoxyethanol, has been studied in guinea pigs. The experiments demonstrate that a distinct but weak sensitizing potency exists for Euxyl K 400 and dibromodicyanobutane. Phenoxyethanol remained almost negative. These results are in good accordance with the low number of cases of allergic contact dermatitis due to Euxyl K 400 and dibromodicyanobutane described since their introduction on the market. Cases of phenoxyethanol contact allergy have been published hitherto only 4x in the medical literature. PMID- 8462292 TI - Allergic contact dermatitis from natural latex without contact urticaria. AB - During the last decade, there have been many reports of immediate-type hypersensitivity to natural latex, resulting in contact urticaria, generalized allergic reactions such as urticaria and Quincke's edema, and asthmatic or anaphylactic reactions. Moreover, delayed-type hypersensitivity to rubber additives such as thiuram and carbamate derivatives is acknowledged to be the main cause of dermatitis in patients working with rubber gloves. We here report on a patient who developed severe dermatitis on his hands and forearms 3 months after he had started working with rubber gloves. Patch tests with rubber additives, skin prick tests and RAST to natural latex were negative. However, a delayed type of hypersensitivity to latex could be shown by a positive patch test. To our knowledge this is the 1st case reported of an isolated contact dermatitis from natural latex without contact urticaria to latex or hypersensitivity to rubber additives. We therefore propose that not only patch tests with rubber additives, but also skin prick and patch tests with latex should be performed in contact dermatitis patients working with rubber gloves. PMID- 8462293 TI - Contact dermatitis from beryllium in dental alloys. AB - An increasing number of metals with the potential to cause allergic contact dermatitis have found their way into dental alloys for economic and practical reasons. 2 patients are reported who developed gingivitis adjacent to the Rexillium III alloy in their dental prostheses. Patch testing demonstrated positive reactions to beryllium sulfate, a component of the alloy. Components of dental alloys and the mechanism of the contact dermatitis are discussed. PMID- 8462294 TI - Palladium in dental alloys--the dermatologists' responsibility to warn? AB - Palladium is increasingly used in industry, but also in fine jewelry and in dentistry. Thus, palladium-silver alloys comprise a substantial part of the noble metal ceramic alloy sales in Western countries. The increased use of this metal seems, however, to be paralleled by a rise in the number of reports of palladium allergy. Recently a European study reported a sensitization rate of 2.8%. In Austria, where palladium has started to displace amalgam in dental fillings because of concerns about mercury toxicity, and gold due to price factors, we have found a sensitization rate of 8.3% in unselected eczema patients. Despite the current lack of clear clinical relevance of this finding, these numbers should motivate us to question this substance as "the alloy of the future". PMID- 8462295 TI - Lichenoid dermatitis in 3 professional footballers. AB - We describe 3 professional footballers who developed lichenoid dermatitis over a short period of time. Clinically, the eruption in all 3 of them can be classified as lichenoid photodermatitis. We suggest an influence of possible contact allergens or photo-active substances. Histologic evidence points to features of classical lichen planus with purpura, typical of lichen aureus (purpuricus), but showing some clinical and morphological differences. PMID- 8462296 TI - Contact allergy to disperse blue 106 and blue 124 in black "velvet" clothes. AB - 9 cases of allergic contact dermatitis due to black "velvet" fabrics, mostly leggings, are reported. In all cases, the 2 disperse dyes Blue 106 and 124 were shown to be the responsible contact sensitizers. Preparation of a chloroform extract and separation of the different disperse dyes by analytical and preparative thin-layer chromatography showed that 8 of the 9 black "velvet" clothes contained the same composition, namely Disperse Blue 1, 106, and 124, Disperse Red 1 and Disperse Yellow 3. In experimental studies performed previously, Disperse Blue 124 has been demonstrated to be a moderate sensitizer while Disperse Blue 106 proved to be the strongest sensitizer found so far among the azo disperse dyes. PMID- 8462297 TI - Contact allergies to topical corticosteroids. AB - The patient, a 34-year-old Japanese woman who noticed worsening of her rash after using topical corticosteroid preparations on her neck, was patch tested for both commercial preparations and corticosteroids themselves. The patch test results revealed that she had a contact allergy to gold, oxytetracycline, and 2 types of corticosteroid (acetonides and esters) in 7 compounds (betamethasone valerate and dipropionate, hydrocortisone butyrate and hydrocortisone butyrate propionate, amcinonide, budesonide, and fluocinonide). PMID- 8462298 TI - Allergic reactions to a hairdressers' series: results from 9 European centres. The European Environmental and Contact Dermatitis Research Group (EECDRG). AB - To obtain data on the frequency of sensitization among European hairdressers, the patch test results from 9 centres were evaluated. 8 allergens recommended by the ICDRG and EECDRG in the hairdressing series and PPD from the standard series were used to patch test 809 hairdressers and 104 clients suspected of contact sensitization. Among hairdressers, the mean frequencies of sensitization ranked as follows: GMT 19%, PPD 15%, APS 8%, PTD 8%, ONPPD 4% and PADH 4%. In contrast to GMT in acid permanent waves, the frequency of sensitization to AMT in alkaline permanent waves was only 4%. Frequencies of sensitization to pyrogallol and resorcinol were 0.8% and 0.6%, respectively. The frequencies of sensitization showed marked regional variations, particularly that to GMT, which was highest in Germany (51%), followed by Spain (22%) and London (19%). Clients of hairdressers showed a similar rank order of sensitization frequency, with the exception of APS, which was completely negative in this (small) series. PMID- 8462299 TI - Contact urticaria from watermelon in a patient with pollen allergy. PMID- 8462300 TI - Allergic contact dermatitis due to plant extracts in a multisensitized patient. PMID- 8462301 TI - Contact allergy to benzyl alcohol and benzyl paraben. PMID- 8462302 TI - Repeated patch testing in delayed hypersensitivity to beta-lactam antibiotics. PMID- 8462303 TI - Reaction to topical lignocaine in a patient with contact dermatitis. PMID- 8462304 TI - Allergic contact dermatitis due to lanolin in an adhesive plaster. PMID- 8462305 TI - Allergic contact dermatitis from ethylbutylthiourea in neoprene. PMID- 8462306 TI - Contact dermatitis in a cast technician. PMID- 8462307 TI - Frequency of HLA antigens in persons sensitive to N-isopropyl-N'-phenyl-p phenylenediamine (IPPD). PMID- 8462308 TI - Airborne allergic contact dermatitis from benzalkonium chloride. PMID- 8462309 TI - Delayed prolonged contact urticaria from the elm tree. PMID- 8462310 TI - Allergic contact dermatitis due to para-tertiary-butylphenol-formaldehyde resin in a hearing aid. PMID- 8462311 TI - Antagonism in concentrated surfactant systems. PMID- 8462312 TI - Systemically aggravated contact dermatitis caused by aluminium in toothpaste. PMID- 8462313 TI - A strange manifestation of occupational contact urticaria due to mouse hair. PMID- 8462314 TI - Contraception in older woman. AB - Oral contraception (OC) in the premenopause has been recently proposed as treatment for control and prevention of the putative symptoms typical of this period of life. Indeed, menstrual cycle disturbances and climacteric symptoms frequently occur at this age. The major aim of normal contraception is resultant maintenance of normal sexual activity. The effects of one OC containing 20 mcg ethinylestradiol and 150 mcg desogestrel (EE/DOG) were studied. Treatment did not significantly modify both lipid metabolism (triglycerides, total cholesterol, HDL, LDL, Apo A, Apo B) and clotting system (fibrinogen, PT, PTT, antithrombin III, fibrinopeptide A). No significant modifications of oral glucose tolerance test (OGGT) occurred after EE/DOG treatment. Also, bone density was not modified during estro-progestinic administration. From our experience, if there are no risk factors such as smoking, obesity or hypertension, the OCs could be used until menopause for absolute contraceptive efficacy, good tolerance and lack of side effects. PMID- 8462315 TI - Oral contraceptive use and breast cancer in Indonesia. AB - A hospital-based case-control study was conducted in Ujungpandang, Indonesia, to determine the association of breast cancer and current and former oral contraceptive (OC) use. This study included 119 newly diagnosed, histologically confirmed, breast cancer cases who were admitted to the four largest referral hospitals in Ujungpandang from 1990-1991. Controls were 258 women admitted to these same four hospitals with diagnoses unrelated to breast cancer or OC use. Thirty cases (32%) and 55 (19%) controls reported having ever used OCs. The odds ratio for ever using OCs and breast cancer was 1.8 (95% confidence interval 1.2 3.0) after adjustment for age, age at first pregnancy, and family history of breast cancer. Increasing duration of OC use did not increase risk of breast cancer. No latency trend of increasing years since first OC use among cases was observed; however, a younger age at first OC use was associated with increasing breast cancer risk. A significant recency effect was observed; women last using OCs within five years of study enrollment were at greatest risk of breast cancer (OR = 4.9, 95% CI: 2.1-11.4). This first study of breast cancer and OC use in Indonesia does not provide consistent data to indicate an increased risk of breast cancer associated with OC use. Although breast cancer cases were 80% more likely to have ever used OCs, neither duration nor latency of OC use were associated with cancer risk. The significant recency effect suggests that a detection bias might explain the observed relationship between ever OC use and breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462316 TI - Release characteristics, ovarian activity and menstrual bleeding pattern with a single contraceptive implant releasing 3-ketodesogestrel. AB - The properties of a single contraceptive subdermal implant releasing 3 ketodesogestrel were assessed in fifteen women over twelve months. Serum levels of 3-ketodesogestrel were monitored regularly following insertion and after removal. The mean serum level of 3-ketodesogestrel was 245 pg/ml after 72 h (steady state) and 176 pg/ml after twelve months. All volunteers demonstrated ovulation inhibition throughout the study. Transient oestradiol peaks occurred during the study. No luteal activity was noted. The cervical mucus was rapidly rendered hostile to sperm migration. Two women withdrew from the study during the first six months for medical reasons. Both volunteers cited bleeding irregularity as the main cause, one complaining of oligomenorrhoea, the other of prolonged bleeding/spotting episodes. A small but significant increase in weight was noted during the study period. PMID- 8462317 TI - Influence of gestodene and desogestrel as components of low-dose oral contraceptives on the pharmacokinetics of ethinyl estradiol (EE2), on serum CBG and on urinary cortisol and 6 beta-hydroxycortisol. AB - A randomized controlled clinical trial was undertaken over a 6-month treatment period with two low-dose combined oral contraceptives (OC) to investigate whether the metabolism and elimination of ethinyl estradiol (EE2) is differently influenced by the two progestational components gestodene (G) and desogestrel (D), an issue which has been very controversial recently. The two formulations contained 30 micrograms EE2 each, together with either 75 micrograms G or 150 micrograms D. Of the 40 young women recruited for each formulation, 31 of each group were available for statistical evaluation. The pharmacokinetics of serum EE2 were studied on day 1, 10 and 21 of cycle 1, 3 and 6. There were no significant differences between the two groups in any cycle with respect to parameters measured. This was true for the distinct intracyclical rise in the mean EE2 serum levels from day 1 to day 10 and the smaller further increase between day 10 and day 21, with no change in this respect between the cycles studied. Respective changes were seen with regard to the area under the EE2 serum concentration curve up to 4 and 24 hours (AUC0-4 and AUC0-24), cmax and tmax of serum EE2. The estrogen-dependent corticoid-binding globulin (CBG) increased similarly in the two groups intracyclically and slightly also intercyclically at all times tested. Except for the first treatment cycle, urinary excretion of cortisol and 6 beta-hydroxycortisol displayed a tendency to lower values intracyclically as well as intercyclically, again with no differences between the two groups. Also, the 6 beta-hydroxycortisol-to-cortisol ratio was not different between the groups, showing a slight tendency to rise from about 4 at the beginning of the medication to around 5.5 at the end of the 6th treatment cycle in both groups. It is concluded that G and D as components of low-dose OCs exert comparable effects on the metabolism and elimination of EE2. PMID- 8462318 TI - Effect of antiprogestin, hCG and a prostaglandin analogue on human uterine contractility. AB - In the present study, the effect of hCG and RU 486 on non-pregnant uterine contractility and the sensitivity of the myometrium to the prostaglandin analogue misoprostol (GD Searle, Chicago, IL, USA) was evaluated. Seven healthy female volunteers participated in the study. Uterine contractility was recorded on cycle day LH+13 in two cycles. After recording the spontaneous contractility, 200 micrograms and 400 micrograms of misoprostol were administered orally at an interval of 45-60 minutes. In the second month, 5,000 IU hCG was administered on cycle day LH+8 and 10,000 hCG on cycle days LH+10 and LH+12, and 200 mg RU 486 on cycle day LH+11, 48 hours prior to the recording. In three women, a third month was included in which the same treatment, except for RU 486, was given. Treatment with hCG delayed menstrual bleeding and resulted in a significant increase in the concentration of plasma progesterone. Following hCG, the degree of uterine contractility was reduced, while after hCG and RU 486 the uterus was significantly more active. In the control cycle and following hCG alone, misoprostol had a slight stimulatory effect. When RU 486 was added, the degree of contractility following misoprostol was 4 to 9 times greater than that found if RU 486 was not given. Late luteal administration of RU 486 is not an effective method of fertility regulation. The results of the present study indicate that a combination of RU 486 and misoprostol will be more suitable for this purpose. PMID- 8462319 TI - Intravasal application of BCG (Bacille Calmette Guerin) is not an effective method for control of fertility in the male: a preliminary report. AB - Bacille Calmette Guerin (BCG) was applied intravasally in male rats with the hope of developing a method for control of fertility in the male. Our results, however, suggest that this approach is not feasible for control of male fertility. PMID- 8462320 TI - Tamoxifen as an antifertility agent in the long-tailed macaque (Macaca fascicularis). AB - The potential use of tamoxifen, a nonsteroidal antiestrogen, as an antifertility agent was studied in the long-tailed macaque (Macaca fascicularis). Twenty-six cycling females were bred, then treated with a single oral dose of tamoxifen (5 mg/kg) (N = 13) or vehicle (N = 13) on day 4 post-ovulation. Serum progesterone (P4) and tamoxifen concentrations were evaluated on post-ovulation days 4, 8, 12, 16, and 18. No effects of treatment were observed on P4 concentrations or on the fertility rate--pregnancy was achieved in 4/13 controls (31%) and 6/13 treated females (46%). Analysis for serum tamoxifen concentrations in samples collected during the fertility and a supplemental pharmacokinetic study (N = 3; single oral dose of 10 mg/kg; urine and serum evaluated) failed to reveal any detectable tamoxifen levels. It was concluded that (1) absorption of tamoxifen may be negligible under the described treatment regimens or (2) tamoxifen metabolism/clearance occurs at a rapid rate. PMID- 8462321 TI - Additive effect of RU 486 and anordrin on pregnancy interruption in the mouse. AB - The effect of various doses of anordrin and RU 486, alone or combined, on serum progesterone (P) levels, fetal resorption, and recovery of ovulation was studied in mice. Each drug was given as a single sc injection on day 7 of pregnancy and autopsy was performed on days 8, 9, or 11. Serum P was normal at 24 h but fell significantly 48 h after treatment with anordrin (0.05 mg). Doses of 0.05 or 0.2 mg anordrin were effective in interrupting pregnancy in 30% and 70% of pregnant mice, respectively. RU 486, 0.01 mg per mouse, induced a pronounced decrease of P levels 24 h after treatment and interrupted pregnancy in 50% of pregnant mice. The combined treatment with submaximal doses of anordrin plus RU 486 did not further decrease P levels, but increased the proportion of mice with fetal resorptions to 90%. The combination of small doses of anordrin with RU 486 had an additive effect on pregnancy termination. The additive effect required a dose of RU 486 above the threshold level. Direct observation of aborted fetuses indicated that the resorptive process occurred earlier with RU 486 than with anordrin. Recovery of ovulation was associated with pregnancy termination in a high proportion of mice treated with either drug or their combination. PMID- 8462322 TI - Commentary: ethics, ethics everywhere--ascertainment bias in new disorders. PMID- 8462323 TI - Approach to the diagnosis and staging of mediastinal masses. AB - Improvements in cytologic techniques have made needle biopsy much more helpful in diagnosing mediastinal masses. We have added thoracoscopy to the surgical armamentarium. Tumor markers facilitate accurate diagnosis. In the field of imaging, cysts can now be identified almost certainly and aspirated. Magnetic resonance imaging has changed the workup of patients with posterior mediastinal masses. Staging investigations should be based on the type of tumor and the likelihood of spread. PMID- 8462324 TI - Current therapy for thymoma. AB - Thymomas are the most frequently encountered neoplasm of the anterior mediastinum. Thymic neoplasms can be divided into 3 broad categories based on histologic appearance and behavior. Thymomas are tumors with benign-appearing cellular features. If there is no gross or microscopic invasion beyond the capsule, the tumor is considered benign. Any tumor with gross or microscopic invasion through the capsule is considered malignant. In a third category, thymic tumors which have histologically malignant epithelial features, are considered thymic carcinomas and generally have an adverse prognosis. Microscopically, thymomas consist of a variable component of lymphocytic, epithelial, and fusiform (spindle) cell elements. The tumors may be classified according to the predominant cell type or are considered mixed if no cell type predominates. Prognosis is most strongly linked to clinical stage. The role of adjuvant radiotherapy or chemotherapy in the treatment of such tumors is controversial, but malignant thymomas are generally responsive to radiotherapy. Associated myasthenia gravis does not adversely affect the prognosis of thymoma, and medical attention to the myasthenia may contribute to earlier diagnosis of the thymoma. Cisplatin-based chemotherapy may be used to treat advanced disease with a modest response rate. PMID- 8462325 TI - Preoperative assessment of patients undergoing pulmonary resection. AB - A careful preoperative assessment of patients with lung cancer is essential for identifying those at high risk for morbidity and mortality related to the surgical procedure. The clinician must assess the risk associated with such treatment, decide whether the risk is prohibitive, and institute therapy to reduce such risk. Testing modalities used in the preoperative evaluation include spirometry, full pulmonary function tests, measurement of arterial blood gases, radionuclide lung scanning, exercise testing, invasive measurement of pulmonary artery pressure, and a variety of studies involving lobar occlusion or lateral position testing. Studies evaluating the utility of these procedures are reviewed. Additionally, the impact of advanced age on postsurgical outcome is evaluated, as are the possibility of operating on high-risk patients and the use of preoperative interventions. PMID- 8462326 TI - New approaches to Pancoast and chest wall tumors. AB - Superior pulmonary sulcus carcinoma, or Pancoast's tumor, was first identified in 1932 by H. K. Pancoast, who described a small tumor at the apex of the lung producing a characteristic pain pattern and rapid, universal mortality. Despite early indications that this type of carcinoma was amenable to neither radiation nor surgery, the current treatment approach calls for irradiation therapy (3,000 rad over 2 to 3 weeks) followed by surgical resection of the chest wall, lower brachial plexus, and en bloc resection of the lung. In selected patients with negative mediastinal nodes, this approach has been associated with a 34% 5-year and a 29% 10-year survival. PMID- 8462327 TI - Solitary brain metastases. Radiation, resection, or radiosurgery? AB - Three treatment options are available for management of the patient with a known thoracic mass and a solitary brain metastasis: external beam radiation, surgical resection, and stereotactic radiosurgery. Traditional external beam radiation may still represent the most appropriate choice in the management of patients with radiosensitive lesions who are in poor health or who have significant risk factors that prohibit other treatment choices. Surgery is recommended in the presence of significant edema, a large intracranial mass, significant symptoms requiring immediate attention, associated hemorrhage, and for superficial lesions. Finally, stereotactic radiosurgery, an important new technique whereby high doses of radiation are targeted directly to the mass, is recommended particularly for deep lesions that are difficult to reach surgically and for treatment of patients for whom surgery is contraindicated. Stereotactic radiosurgery has the added benefits of being noninvasive, effective, and repeatable in the presence of recurrence or other metastatic disease. PMID- 8462328 TI - Natural history and epidemiology of malignant mesothelioma. AB - Asbestos exposure constitutes the primary cause of pleural and peritoneal mesothelioma in humans. Risk relates to the duration and intensity of exposure. Thus, those exposed at younger ages are at higher lifetime risk. Families of asbestos workers exposed to asbestos on hair and clothing as well as to asbestos items brought home from the workplace are also at risk, as are employees working in the same vicinity as asbestos workers. The public health significance of exposure from asbestos in public and private buildings remains controversial. Malignant mesothelioma is difficult to diagnose and carries a poor prognosis. Chemotherapy with single or multiple agents has thus far been disappointing, but doxorubicin and cisplatin or mitomycin and cisplatin are probably most active with response rates in measurable disease of 25%. Palliative radiotherapy is also problematic since differences between tumor cytotoxicity and pulmonary tolerance are small and radiation pneumonitis may significantly impair quality of life. PMID- 8462329 TI - Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma. AB - The use of extrapleural pneumonectomy in a multimodality treatment setting for malignant pleural mesothelioma is described, presenting first the right-sided approach and then the left-sided. This technique used in a multimodality approach with CAP chemotherapy (cyclophosphamide 600 mg/m2, doxorubicin 60 mg/m2, cisplatin 75 mg/m2) 5 cycles at 3-week intervals, and radiotherapy (55 Gy radiation to sites of previous bulky disease or residual disease) to treat 44 patients with malignant pleural mesothelioma resulted in improved operative mortality and decreased length of hospital stay. PMID- 8462330 TI - Pleurectomy/decortication and adjuvant therapy for malignant mesothelioma. AB - Malignant mesothelioma is an uncommon and usually fatal cancer, for which there is no standard treatment. However, surgical resection remains the mainstay of treatment because of the inability to treat the entire hemithorax effectively with radiation and the lack of effective chemotherapy drugs. Extrapleural pneumonectomy is the only technically feasible operation for patients who have bulky local tumor and chronic entrapment of the lung, but pleurectomy/decortication is associated with a lower operative morbidity and mortality, and seems to lead to an equally good survival in patients who have early-stage disease. Because of the high risk of local recurrence after surgical resection by either extrapleural pneumonectomy or pleurectomy/decortication, efforts have been directed at developing effective adjuvant treatment. Radiation given postoperatively after pleurectomy/decortication has led to a minimal improvement in survival and to significant side effects. Adjuvant chemotherapy is considered investigational but is currently being evaluated in a clinical trial using high-dose intrapleural and systemic chemotherapy after pleurectomy/decortication. Additional well-designed prospective trials are needed to alter the dismal outcome of this disease. PMID- 8462331 TI - Video thoracoscopic management of benign and malignant pericardial effusions. AB - Surgical management of symptomatic benign and malignant effusive pericarditis is often required. Twenty-two patients with medically recalcitrant effusive, nonconstrictive pericarditis underwent pericardial resection by a video-assisted thoracoscopic surgical (VATS) technique (9 malignant, 13 benign). Pericardiectomy, resulting in complete drainage of the pericardial space and control of patient symptoms was accomplished routinely. Ipsilateral pleural effusions, originally present in 11 patients, were also managed. The VATS pericardiectomy was well tolerated even by gravely ill patients. This approach should be considered as an alternative to lateral thoracotomy or subxiphoid pericardial window for the surgical management of patients with symptomatic benign and malignant pericardial effusions. PMID- 8462332 TI - Approach to the patient who presents with superior vena cava obstruction. AB - Obstruction of the superior vena cava (SVC), a thin-walled vessel that carries blood at low pressure, may result from compression by tumor or intraluminal thrombus formation. The SVC syndrome that ensures may be the cause of significant morbidity. This article reviews the pathogenesis of SVC syndrome, appropriate radiologic imaging procedures, and the issue of obtaining a tissue diagnosis. The management of SVC syndrome with chemotherapy, radiotherapy, and surgery is also discussed. PMID- 8462333 TI - Synchronous primary lung cancers. AB - Synchronous primary lung cancers (SPLCs) occur in up to 0.5% of patients with lung cancer. They are first diagnosed intraoperatively or upon pathologic examination of resected tissue in up to 40% of patients with SPLCs. Complete surgical resection is possible in over 90% of patients, with an operative mortality of 2.1%. Despite a high frequency of early stage disease (two thirds of patients have either stage I or II tumors), surgical therapy yields an overall 5 year survival of only 20%, far lower than expected. These findings suggest that the biology of SPLCs is different from that of ordinary lung cancers, or that the diagnosis of SPLCs is being made too often, and that in some patients the second cancer focus actually represents metastatic disease. The use of newer techniques of identifying the molecular and biologic characteristics of these cancers, including analysis of DNA ploidy patterns, may more accurately define SPLC patients. Optimal interventional and preventive therapies remain to be determined. PMID- 8462334 TI - Pulmonary metastectomy. Current indications for removing lung metastases. AB - Despite a great deal of literature on pulmonary metastectomy, the treatment of pulmonary metastases remains somewhat controversial. However, review of the literature does allow the development of certain algorithms to approach this problem, and these are discussed. PMID- 8462335 TI - Overview: the changing nature of esophageal cancer. AB - Squamous cell carcinomas of the esophagus, while still frequent in many locations throughout the world, now comprise a smaller percentage of esophageal cancers in the United States than was previously believed. Such tumors occur most often in black men and in association with tobacco and alcohol abuse. Adenocarcinomas of the distal esophagus represent an increasing proportion of esophageal tumors. These neoplasms arise in columnar epithelium (ie, Barrett's esophagus) or extend into the esophagus from their site of origin in the proximal stomach. Esophageal adenocarcinomas appear more often in white than black subjects and in men more than women. The clinical features and diagnostic approaches to squamous cell tumors and adenocarcinomas of the esophagus are similar. PMID- 8462336 TI - Multimodality therapy for esophageal carcinoma--update. AB - Transhiatal esophagectomy with mobilization of the stomach to replace the esophagus has been used to provide palliation of dysphagia at the University of Michigan for more than 15 years. The subtotal esophageal resection is believed to be preferable to the transthoracic approach that has been considered the standard for this surgery. As experience with the technique has increased, complications have decreased. Most patients are discharged, able to swallow, by the 10th or 11th postoperative day. Survival in these patients is no worse than that reported after more traditional transthoracic esophagectomy, and the transhiatal route has reduced postoperative pulmonary complications and the incidence of mediastinitis from anastomotic leak, which is fatal in 50% of patients. In a phase II trial of preoperative combined radiation therapy and chemotherapy with cisplatin, vinblastine, and continuous-infusion 5-fluorouracil in 45 patients, survival after esophagectomy seemed considerably better than in our historical control subjects treated with transhiatal esophagectomy alone. The 3-year survival of the 43 patients was 46% compared with 23% of those who received only surgery. Considering only the 27% of those patients who had no cancer in their resected specimens, ie, the complete responders, the 5-year survival is 70%. A phase III trial is now accruing patients in an attempt to confirm these results. PMID- 8462337 TI - Selecting the surgical approach to cancer of the esophagus. AB - Surgical treatment of cancer of the esophagus is influenced by two issues: use of surgical resection within a multimodality treatment approach and selection of the correct surgical approach. Selecting the correct surgical approach should be individualized and determined by the intent of surgery (curative or palliative), the anatomic location of the tumor (cervical or thoracic), the preferred method of reconstruction (colonic interposition or gastric pull-up), and whether surgery is the only therapeutic modality to be used or will be combined with neoadjuvant chemotherapy and/or radiotherapy. A discussion of the efficacy of treatment within a multimodality setting and a description of the surgical approach follow. PMID- 8462338 TI - Sleeve lobectomy, segmentectomy, and thoracoscopy in the management of carcinoma of the lung. AB - In patients with lung cancer, the goals of limited resection procedures of the lung and major airways are to provide an adequate cancer operation while preserving functioning lung tissue. Discussed in this article are sleeve lobectomy, an alternative to pneumonectomy in patients with cancer in a lobar orifice; segmentectomy or wedge resection, an alternative to lobectomy in those with a peripheral lung cancer; and thoracoscopy, an alternative to open thoracotomy for various chest malignancies. PMID- 8462339 TI - The molecular biology of lung cancer pathogenesis. AB - Lung cancers exhibit multiple genetic lesions including mutations activating the dominant cellular proto-oncogenes as well as those inactivating the recessive or "tumor suppressor" genes. Candidate tumor suppressor genes include those on chromosomes 1p, 1q, 3p14, 3p21.3, 3p25 (VHL gene), 5q21 (APC/MCC gene cluster), 9p21-22 (interferon gene cluster), 11p, 13q (rb gene), 16p24, and 17p (p53 gene). Mutations in p53 inactivate its transcriptional activity, while replacement of a wild-type p53 in lung cancer cells inhibits growth and tumorigenicity suggesting that p53 acts as a master growth regulatory switch. Lung cancer cells exhibit several positive autocrine growth factor loops and express nicotine receptors which could function as tumor promoting systems. In addition, they express a negative autocrine loop involving opioids and their receptors which is reversed by nicotine acting through nicotinic acetylcholine receptors. The presence of nicotine receptors suggests nicotine or its metabolites may play a direct role in lung cancer pathogenesis. PMID- 8462341 TI - [Open letter of the chief physician of a university surgical clinic for revision of the public health structure regulation--reduction in compensation for physicians entitled to liquidation]. PMID- 8462340 TI - [Work disability: economic effects of ambulatory surgery]. PMID- 8462342 TI - [Prevention of infection in endoscopic surgery (minimal invasive surgery)]. PMID- 8462344 TI - [Clinic administrator as manager--management in clinic administrations. Thoughts on seminars of the German Society of Surgery]. PMID- 8462343 TI - [Routine bed disinfection is unnecessary. In Freiburg a new model was developed]. PMID- 8462345 TI - [Sale of the practice and patient records. Federal court: leaving patient records is only allowed with patient consent]. PMID- 8462346 TI - [Drainage in surgery of infections]. PMID- 8462347 TI - [Pyogenic liver abscess. Analysis and follow-up examination of a personal patient sample 1981-1992]. AB - From January 1, 1981 to January 1, 1992 a total of 30 liver abscesses were treated in the University Clinic for Surgery in Cologne. 23 patients underwent an primary operative treatment and seven patients received a controlled guided percutaneous drainage. During the observation period four patients (13.3%) died by the effect of the liver abscess. 20 patients (66.7%) were subjected to clinical, laboratorical and computertomographical post examinations. The primary rate of operation success amounted to 47.8%, that of controlled guided percutaneous drainage of 42.8% (NS). The secondary success rate (that means after successful operative reintervention) amounted to 86.9% by the operative and to 85.7% by the percutaneous drainaged cases. During the post examination no relapse was determinated. Larger or chambered liver abscesses as well as extrahepatic spreading required operative drainage and, in cases of multifocal spreading, a resection with concomitant antibiotics. In case of solitary abscesses the controlled guided percutaneous drainage is the least harmful and low-prices method. PMID- 8462348 TI - [Parathyroid gland cancer. Problems in diagnosis and therapy]. AB - Parathyroid carcinoma occurs in 0.1 to 5% as the cause of primary hyperparathyroidism (HPT). It is difficult to determine the true incidence, because parathyroid carcinoma is diagnosed too often due to unreliable histologic criteria. It is only justified to make the diagnosis, when a local recurrence or metastases with the clinical picture of a recurrent or persistent HPT occurred. Treatment of choice is the initial en-bloc resection, which may result in long disease-free intervals. Pharmacological treatment, chemotherapy, and radiation are mostly ineffective in the treatment of parathyroid carcinoma. A satisfactory long-term palliation can only be achieved with repeated resections of the local recurrences and metastases. Diagnostic efforts should be made to localize the recurrent tumor before every reoperation, whereby ultrasonography of the neck is the most sensitive procedure. Occasionally the parathyroid tissue cannot be identified in spite of preoperative diagnostic studies or hypercalcemia persists after surgery. In these cases forced diuresis and medical treatment with calcitonin, diphosphonates or mithramycine can briefly control hypercalcemia. The clinical courses of 3 patients with metastasizing parathyroid carcinoma are presented and discussed. In these patients 3 to 11 surgical interventions were performed in combination with an intermittent medical treatment. By this regimen we achieved long-term palliations up to 13 years. PMID- 8462349 TI - [Endosonography of the anal canal in functional disorders of the pelvic flow. Initial experiences]. AB - Nine patients were examined by anal endosonography for pelvic floor disorder. Internal anal sphincter thickness was correlated with sphincter function. Six patients with idiopathic incontinence showed a reduction of internal anal sphincter thickness, one patient with outlet obstruction due to chronic anal fissure showed an increase of thickness. Traumatic lesions could be precisely localized because of defects in both internal and external anal sphincter. Anal endosonography can be recommended in the evaluation of pelvic floor disorders. PMID- 8462351 TI - [Laparoscopic dissection of the Ladd band in adulthood]. PMID- 8462350 TI - [Surgical treatment and regional chemotherapy in melanoma of the extremities]. AB - Since 1979, our treatment protocol for extremity melanoma includes wide local excision, regional lymph node dissection and hyperthermic limb perfusion. We report on the results of a follow-up of the patients treated in the first decade (n = 451). According to the UICC Classification of 1987, 4% of our patients were in stage I, 36% in stage II, 50% in stage III and 9% in stage IV. The respective 5-year survival rates were 93%, 91%, 49%, and 20%. We conclude that regional chemotherapy appears to be beneficial even for stage II patients, as 5-year survival rates of more than 90% can be achieved. PMID- 8462352 TI - [Congenital post-papillary, membraneous duodenal stenosis as a rare cause of jaundice in adulthood]. PMID- 8462353 TI - [Immunoglobulin administration in preparation for splenectomy in autoimmune thrombocytopenia in childhood]. PMID- 8462354 TI - [A new instrument for extirpation of PTFE vascular prostheses. Initial clinical experiences]. AB - In seven patients in whom a PTFE prosthesis had to be removed (six arteriovenous dialysis shunts in the arm and one femoro-popliteal by-pass), surgery was performed with the aid of a newly developed prosthesis removal device. This device consists of a guide rod that is inserted in the prosthesis while a second, chisel-like extension with a sharp cutting edge is advanced along the exterior of the prosthesis to separate it from the tissue. With this technique, up to 17-cm long segments were extirpated subcutaneously. The only complication was a lesion of an radial artery in an atypically situated AV shunt. The advantages of the new instrument are that it saves time and conserves tissue and skin. PMID- 8462355 TI - [Surgical procedure in Crohn disease]. PMID- 8462356 TI - [Drainage--materials and physical principles]. PMID- 8462357 TI - [Drainage in hepatobiliary surgery]. PMID- 8462358 TI - [Drainage techniques and drainage principles in visceral surgery]. PMID- 8462359 TI - [Drainage in accident and reconstructive surgery]. PMID- 8462361 TI - Concentrating missense mutations in core gene of hepatitis B virus. Evidence for adaptive mutation in chronic hepatitis B virus infection. AB - To elucidate the temporal relationship between liver damage and mutation(s) in hepatitis B virus core gene, serial sera from a progressive liver disease patient and an asymptomatic carrier were studied. By direct sequencing, missense mutations in the core gene were only found in serum from the progressive liver disease patient during the period with frequent exacerbation. Using methods of cloning and sequencing, missense mutations were also found in clones derived from the progressive liver disease patient at a relatively early phase, but strains with a missense mutation from earlier sera did not exist in sera of a later period. Furthermore, there was a tendency of concentrating missense mutations in clones derived from the progressive liver disease patient. These data suggested that missense mutations in the core gene that occurred at an earlier phase might evoke an immune response to eliminate mutated virus and that concentrating missense mutations during a phase of exacerbation might be a result of adaptive mutation. PMID- 8462360 TI - Interferon in the management of chronic hepatitis B. AB - Many drugs have been used in the treatment of chronic hepatitis B, but with the exception of interferon, none have proved to be effective. Several studies have found that a sustained loss of viral replication occurs in approximately 40% of patients who started with a 16-week course of recombinant interferon alfa-2b given in a dose of 5 million units daily or 10 million units three times weekly. Moreover, disappearance of hepatitis B surface antigen in serum has been observed in 10-15% of treated patients. Based on these results, the Food and Drug Administration approved the use of this form of interferon in chronic hepatitis B in July 1992. This article reviews the importance of chronic hepatitis B as a health problem as well as the mechanisms of action, benefits, and adverse effects associated with interferon. Particular emphasis is given to the safety and efficacy data for recombinant interferon alfa-2b. PMID- 8462363 TI - Controlled trial of high-dose octreotide in treatment of acute pancreatitis. Evidence of improvement in disease severity. AB - Nineteen consecutive patients with acute pancreatitis were sequentially allocated to treatment with high-dose octreotide (N = 9) or to act as controls (N = 10). All other aspects of treatment were similar and were according to a strict treatment protocol. There was no significant difference between the two groups on admission with regard to recognized criteria of poor prognosis. The octreotide treated group required significantly less analgesia and after 48 hr developed significantly fewer poor prognostic indicators, including falls in hematocrit of > 10%, in serum albumin to < 32 g/liter, and in serum calcium to < 2.00 mmol/liter. Falls in arterial PO2 to < 10 kPa, in serum albumin of > 20%, and in hemoglobin of > 2 g/dl were also significantly less frequent. There was a trend towards improvement in the octreotide-treated group in every other physiological and radiological indicator of disease severity. High-dose octreotide may reduce the severity of acute pancreatitis. PMID- 8462362 TI - Effect of cyclosporine on distribution of macrophage subpopulations in rat hepatic allograft. AB - Macrophage subpopulations infiltrating the grafts of ACI(RT1a) to LEW(RT1(1)) orthotopic rat liver transplants treated with or without immunosuppressive therapy were studied using immunohistochemical staining. LEW recipients of ACI liver transplants experienced severe acute graft rejection, with a mean survival of only 10.2 +/- 0.7 days. An indirect immunoperoxidase technique on cryostat sections of the liver grafts was used to determine the localization of macrophage subpopulations infiltrating the grafts, as defined by specific anti-rat macrophage monoclonal antibodies, designated TRPM-1 (pan-macrophage), TRPM-3 (activated macrophage) and Ki-M2R (tissue macrophage). TRPM-1+ or TRPM-3+ cells gradually increased on days 5 and 7 in the untreated hepatic allografts, whereas no significant changes in the number of these cells were observed in the isografts. Treatment with cyclosporine (CsA) greatly decreased the number of these two different types of cells infiltrating the hepatic allografts, compared to the untreated hepatic allografts or the isografts. The time course of the accumulation of these cells in the allografts treated with CsA showed a similar pattern; the cells increased gradually by day 5 and thereafter decreased. This pattern is different from that observed in the untreated allografts or in the isografts. There was no significant difference in the number of Ki-M2R+ cells between the untreated hepatic allografts and the isografts. However, the number of the Ki-M2R+ cells in the hepatic allografts treated with CsA was much less than that of either the untreated allografts or the isografts. These findings suggest that a progressive relative increase in host TRPM-3+ macrophage is a characteristic feature of ongoing first-set rejection in the rat hepatic allograft.2+ allograft, even when compared with the isografts. PMID- 8462364 TI - Morphological changes of small pancreatic cysts in response to secretin stimulation. Observation by endoscopic ultrasonography. AB - It is difficult to discriminate clinically the etiology of small pancreatic cysts using conventional methods. Endoscopic ultrasonography can delineate small lesions. In order to help differentiate the etiology of cystic lesions of the pancreas by endoscopic ultrasonography, we investigated morphological changes following stimulation of the pancreatic secretion with secretin. After an intravenous injection of secretin (50 CU), the size, shape, and echogenicity of a cyst smaller than 2 cm were recorded for 15 min. Of 17 cases examined, 10 patients showed an alteration of these factors. These cases were thought to be nonneoplastic cysts, which included all six cases where communication to the main pancreatic duct was demonstrated by ERCP. Five cases of neoplastic cyst did not show the change in shape and size. These results indicate that secretin stimulation provides useful information in the diagnosis of the etiology of pancreatic cyst by endoscopic ultrasonography. PMID- 8462365 TI - Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. AB - We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78-107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110 +/- 14 pmol/liter (mean +/- SEM). Truncated GLP 1 significantly inhibited postprandial acid secretion by 43 +/- 11% in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16 +/- 2 min to 30 +/- 5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47 +/- 17% and 40 +/- 9% during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 +/- 0.2 versus 3.7 +/- 0.3), indicating that GLP 1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man. PMID- 8462366 TI - Regulation of intestinal concentration of cholecystokinin by bile and/or pancreatic juice. AB - Pancreatic exocrine secretion in conscious rats is regulated by intraluminal bile and/or pancreatic juice. Exclusion of bile and/or pancreatic juice from the intestinal lumen caused cholecystokinin (CCK) release and stimulated pancreatic secretion. CCK in the plasma is mainly derived from endocrine cells in the proximal small intestinal mucosa. We examined the changes in CCK concentrations in the intestinal mucosa and compared them to those of plasma CCK concentrations and the changes of luminal trypsin activities after bile and/or pancreatic juice diversion in conscious rats. Rats with bile and pancreatic fistulae were used. Each treatment of bile, pancreatic juice, and bile-pancreatic juice diversion decreased luminal trypsin activity and increased plasma and intestinal CCK concentrations. The potency of the stimulatory effect on plasma and intestinal CCK concentrations was bile-pancreatic juice diversion > pancreatic juice diversion > or = bile diversion. Neither plasma CCK concentration nor intestinal CCK concentration was in inverse proportion to trypsin activity. The plasma CCK concentration did not parallel intestinal CCK concentration. Intravenous infusion of CCK-8 (300 pmol/kg/hr) did not increase CCK concentration in the intestinal mucosa. It was proposed that bile and/or pancreatic juice in the intestinal lumen regulated CCK concentrations not only in the plasma but also in the intestinal mucosa. PMID- 8462367 TI - Prevalence of gallstone disease in Mexico. A necropsy study. AB - The prevalence of gallstone disease in Mexico was investigated by studying a sample of 21,446 necropsies performed at the Department of Pathology of the General Hospital of Mexico City during a 35-year period (1953-1988). For each decade, 1000 necropsy cases were randomly selected. The crude prevalence of gallstone disease was 14.3%, 8.5% for males and 20.4% for females. The age groups ranged from 20 to more than 80 years old; the age-standardized prevalence for males was 5.6% and for females 16.2%. These rates are intermediate between those found in Chile and some African countries, comparable to some European studies, and less than those found in Mexican-Americans. No significant trend in the prevalence of gallstone disease was found when the different decades were compared. PMID- 8462368 TI - Stabilization of biliary lipid particles by ursodeoxycholic acid. Prolonged nucleation time in human gallbladder bile. AB - We evaluated the effect of ursodeoxycholic acid on the metastability of human bile as reflected by nucleation time and also assessed the mechanism of its action in an ultrastructural study. Ursodeoxycholic acid significantly prolonged the nucleation time of gallbladder bile from cholesterol gallstone patients without causing either drastic changes in the distribution of cholesterol between the nonmicellar and micellar fractions of bile or biliary cholesterol desaturation. Gel permeation chromatography resolved two distinct components of the nonmicellar fraction: vesicles and phospholipid lamellae (identified by electron microscopy). Nonmicellar cholesterol was predominantly carried by vesicles in the bile of untreated gallstone patients, whereas it was chiefly carried by phospholipid lamellae in patients treated with ursodeoxycholic acid. Furthermore, phospholipid lamellae from untreated gallstone patients showed rapid transformation and cholesterol microcrystal formation within seven days, whereas the lamellae from ursodeoxycholic acid-treated patients were stabilized and showed little change. On the other hand, biliary mucin concentration was reduced by the treatment with ursodeoxycholic acid. These findings suggest that ursodeoxycholic acid stabilizes phospholipid lamellae and consequently prolongs nucleation time. It is also possible that the reduction of biliary mucin plays a role in this process. PMID- 8462369 TI - Neuropeptides in pig sphincter of Oddi, bile duct, gallbladder, and duodenum. AB - To better understand the complex structure and function of the sphincter of Oddi (SO), the occurrence and localization of nine neuropeptides, including vasoactive intestinal polypeptide (VIP), bombesin, neuropeptide Y, peptide histidine isoleucine (PHI), calcitonin gene-related peptide (CGRP), galanin, substance P, serotonin, and somatostatin, were studied by immunohistochemical methods in the pig SO. The SO innervation was compared to gallbladder, common bile duct, and duodenal innervation. Specimens from the SO, gallbladder, common bile duct, and duodenum demonstrated a rich network of nerves, as suggested by light microscopy and confirmed by a myelin marker S-100. SO demonstrated very strong immunoreactivity for VIP, strong immunoreactivity for neuropeptide Y and galanin, moderate immunoreactivity for PHI and CGRP, and borderline immunoreactivity for bombesin and substance P. Serotonin and somatostatin immunoreactivity was also observed, not in the nerves, but in some of the epithelial cells. The gallbladder innervation was virtually identical to the SO innervation, whereas common bile duct and duodenal innervation were slightly different. To our knowledge this is the first time that galanin- and PHI-like immunoreactivities have been observed in the SO. Our observations suggest that these peptides, along with VIP, neuropeptide Y, and CGRP, might play a role in the neural control of biliary motility. PMID- 8462370 TI - Mechanism of intragastric tetramethylammonium protection against 40% ethanol injury in rat stomach. AB - The effect of tetramethylammonium (TMA), a ganglionic stimulant, on gastric mucosal injury induced by 40% ethanol was examined. In studies I-III, rats were treated with intragastric vehicle or TMA (1 or 10 mg/kg). In study I, 1 hr after the treatment, 40% ethanol was given intragastrically. The length of the linear corpus mucosal lesions was measured unbiasedly with a caliper after another hour. In study II, mean blood pressure was assessed before and after the treatment. In study III, 1 hr after the treatment, gastric mucus and juice volumes, and titratable acid were measured. In study IV, 40% ethanol (10 ml/kg) was administered intragastrically immediately after 0.2 or 1.4 ml of intragastric vehicle treatment. One hour later, gastric lesions score was assessed as in study I. Results show that (1) intragastric TMA dose-dependently protected against 40% ethanol-induced gastric injury; (2) neither dose of intragastric TMA increased mean blood pressure; (3) there was a dose-related increase in gastric mucus secretion for TMA 1 and 10 mg/kg, and a significant increase in gastric juice volume only for TMA 10 mg/kg; and (4) the rats treated with 1.4 ml of vehicle plus 40% ethanol had significantly less injury than those treated with 0.2 ml of vehicle plus 40% ethanol. We conclude that the protective effect of intragastric TMA can be explained by its dose-related effect in enhancing gastric mucus secretion for TMA 1 and 10 mg/kg and the significantly greater increase in gastric juice volume for TMA 10 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462371 TI - Effects of compound U74500A in animal models of gastric and duodenal ulceration. AB - Pretreatment with U74500A (up to 0.65 mg/100 g) failed to affect gastric lesions induced by 100% EtOH gavage in Sprague-Dawley rats. Topical application of U74500A did not reduce lesions induced by 40% EtOH in ex vivo gastric chamber preparations. However, pretreatment of rats with U74500A (0.65 g/100 g per os) reduced the incidence and severity of experimental duodenal ulcer induced by cysteamine HCl, and duodenal ulcer induced by cysteamine-HCl plus GABA. These results show U74500A to have powerful and specific antiduodenal ulcer actions. Pharmacologic analysis of organ-bath preparations of the small intestine show this compound to reduce intestinal contractility to applied cholinergic and serotonergic agonists. However, relaxations induced by electrical or nicotinic ganglionic stimulation were unaffected. U74500A itself caused concentration dependent contractions. PMID- 8462372 TI - Gastroprotective effect of zinc acexamate against damage induced by nonsteroidal antiinflammatory drugs. A morphological study. AB - The gastroprotective effect of zinc acexamate against gastric damage induced by different nonsteroidal antiinflammatory drugs (indomethacin, diclofenac, and piroxicam) was morphologically assessed in the rat glandular stomach by light and scanning electron microscopy. In addition, the capability of these antiinflammatory drugs to inhibit gastric prostaglandin E2 production was compared with their ability to induce gastric lesions. Microscopically, disappearance of mucus glycoprotein and exfoliation of the mucosal surface were the most common findings. Surface ultrastructural lesions varied from minimal lesions of the surface epithelial cells to deep erosions of the gastric mucosa with release of associated cellular elements and sloughing of the denuded lamina propria. Diclofenac elicited the most powerful inhibitory activity on mucosal prostaglandin E2 (98% inhibition vs control), closely followed by piroxicam (97.8%) and indomethacin (91.05%). Pretreatment of animals with zinc acexamate significantly increased the presence of mucus glycoprotein, maintained the continuity of the surface epithelial cells, and decreased the depth of the mucosal erosions. The degree of protection exerted by zinc acexamate varied with the antiinflammatory, but was always evident. PMID- 8462373 TI - Phenytoin-induced chronic hepatitis. AB - Phenytoin has been associated with acute hepatotoxicity. Chronic liver enzyme abnormalities associated with phenytoin have been attributed to enzyme induction. There have been no reports of phenytoin-induced chronic hepatitis. We describe an asymptomatic 52-year-old woman who received phenytoin sodium for 11 years and was found to have elevated serum aminotransferases. Assays for hepatitis A, B, and C were negative. Liver biopsy was performed and showed chronic persistent hepatitis. This documentation of phenytoin-induced chronic persistent hepatitis was proven by histology and its etiology confirmed by drug withdrawal and by rechallenge. Although uncommon, this entity is important to recognize in the differential diagnosis of asymptomatic chronic hepatic enzyme dysfunction. PMID- 8462374 TI - Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis. AB - Diclofenac is a frequently prescribed nonsteroidal antiinflammatory drug (NSAID). Significant hepatotoxicity related to diclofenac may be more common than previously recognized, as three patients with diclofenac-associated hepatitis were seen by one clinician in a single year. All patients were ANA positive during the hepatitis and had histologic features of chronic active hepatitis. Two had been inappropriately treated with corticosteroids. The third patient presented more acutely with jaundice and symptoms of hepatitis. Two of the patients developed the same hepatic reaction when rechallenged with diclofenac. The third patient was changed to tiaprofenic acid, a NSAID of the same family, and redeveloped evidence of hepatotoxicity. All three were subsequently able to take naproxen without liver dysfunction. Diclofenac-induced liver disease may be misdiagnosed. Twenty-six cases of significant hepatic reactions to diclofenac have been previously reported in the literature and are reviewed. Such hepatic reactions to diclofenac and related NSAIDs may be commoner than realized. Introduction of a NSAID of another class appears to be safe. PMID- 8462375 TI - Severe hepatic failure occurring with T61 ingestion in an attempted suicide. Early recovery with the use of intravenous infusion of reduced glutathione. AB - A case of acute hepatic failure following ingestion of the veterinary euthanasia drug T61 is described. Presenting symptoms were drowsiness, disorientation, muscle hypertonia, and upper limb myoclonus, which faded within a few hours. Two days later, acute liver failure occurred, manifested as encephalopathy, jaundice, and a severe coagulopathy. The hepatic damage was thought to be due to the solvent dimethylformamide, which is the only known hepatotoxin included in the preparation utilized in the suicide attempt. High-dose (1.2 g/day) intravenous reduced glutathione was administered, with a rapid improvement of liver function. The patient was discharged after 17 days. Normalization of all liver function tests was achieved within two months. The favorable outcome in this case stands in contrast to the report of a previous case of lethal T61-induced hepatic failure. Although a different amount of dimethylformamide was ingested in each case (0.45 vs 0.60 ml/kg body wt) and individual differences in susceptibility to the effects of the hepatotoxic agent may have played a major role in these two cases, it is not unlikely that the infusion of high doses of glutathione to our patient contributed to her survival and hepatic recovery. PMID- 8462376 TI - Endoscopic incision of intraluminal duodenal diverticulum. Case report of a new technique. PMID- 8462377 TI - Effects of benfluorex on insulin resistance and lipid metabolism in obese type II diabetic patients. AB - OBJECTIVE: To evaluate the change in lipids and insulin sensitivity in 10 obese type II diabetic patients after treatment with benfluorex or placebo for 2 wk. RESEARCH DESIGN AND METHODS: The study had a double-blind, cross-over design. Insulin sensitivity was measured with the euglycemic hyperinsulinemic glucose clamp technique at two different insulin infusion rates: 0.05 (clamp 1) and 0.10 U.kg-1.h-1 (clamp 2). RESULTS: Subanalysis of the glucose infusion rate under steady-state conditions in the last 30 min of clamp 2 yielded a glucose infusion rate of 5.36 and 3.87 mmol.kg-1.min-1 after benfluorex and placebo, respectively (P = 0.018). CONCLUSIONS: Benfluorex increases insulin sensitivity in obese type II diabetic patients. PMID- 8462378 TI - Skin surface pH in intertriginous areas in NIDDM patients. Possible correlation to candidal intertrigo. AB - OBJECTIVE: To compare skin surface pH and moisture in intertriginous areas in diabetic patients and healthy control subjects and to study the relationship between these parameters and candidal infection. RESEARCH DESIGN AND METHODS: We measured the skin surface pH and moisture in the axillary, inframammary, inguinal, and forearm skin with a pH meter with a flat-glass electrode and skin corneometer. The subjects were 50 NIDDM patients from the diabetic outpatient clinic at Beilinson Medical Center, Petah Tiqva, Israel, and 40 healthy control subjects from hospital personnel. The main outcome measures were skin surface pH, skin moisture, and skin culture for Candida. RESULTS: Skin pH in the inguinal and axillary regions was significantly higher in diabetic patients compared with healthy control subjects (P < 0.0001), whereas no difference was noted in the forearm. In the inframammary region, diabetic women had significantly higher pH than nondiabetic women (P < 0.01). No difference was noted in men in this region. Six patients (12%) had candidal infection in intertriginous areas. CONCLUSIONS: Our study indicates that in intertriginous regions, skin surface pH of diabetic patients is significantly higher than in normal control subjects and implies the significance of skin pH as a possible factor promoting host susceptibility to skin candidal infection. PMID- 8462379 TI - Apolipoprotein E polymorphism is associated with plasma cholesterol response in a 7-day hospitalization study for metabolic and dietary control in NIDDM. AB - OBJECTIVE: To investigate the effects of apolipoprotein E phenotype, which is an important genetic factor determining plasma cholesterol level, on plasma lipoprotein metabolism during a 7-day diet therapy of diabetes. RESEARCH DESIGN AND METHODS: Diet therapy was performed in 242 subjects with NIDDM. Plasma lipid levels and apolipoprotein A-I, B, and E levels on hospital days 2 and 9 were compared in three phenotype groups, epsilon 2 (E2/2, and E2/3), epsilon 3 (E3/3), and epsilon 4 (E3/4 and E4/4). RESULTS: No differences were observed in fasting blood glucose level, body mass index, age, duration of NIDDM, or medication among the three phenotype groups. Before starting the treatment, total plasma cholesterol did not vary by apolipoprotein E phenotype, although the mean plasma low-density lipoprotein cholesterol level in epsilon 4 patients was higher than in either epsilon 3 or epsilon 2 patients (epsilon 4, 145 +/- 42; epsilon 3, 131 +/- 34; epsilon 2, 128 +/- 36 mg/dl; P < 0.05). Changes in fasting blood glucose/body mass index after the 7-day treatment were not different among the apolipoprotein E phenotype groups, whereas the decrease in plasma cholesterol level after the treatment was significantly greater in epsilon 2 patients than in either epsilon 3 or epsilon 4 patients (epsilon 2, 10.3 +/- 14.2; epsilon 3, 6.1 +/- 11.0; epsilon 4, 3.8 +/- 9.6%; P < 0.05). CONCLUSIONS: Total plasma cholesterol response to in-hospital diet therapy varies by apolipoprotein E phenotypes, with subjects with apolipoprotein E2 showing the greatest response, whereas those with apolipoprotein E4 show the least. We suggest that subjects with apolipoprotein E4 should be controlled more strictly than other subjects from a viewpoint of reducing plasma cholesterol levels. PMID- 8462380 TI - Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan. AB - OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in the Funagata area of Japan. RESEARCH DESIGN AND METHODS: The total eligible subjects was 1163, all were > or = 45 yr of age, and 52 were known diabetic patients. Data collected included body height, weight, and answers to medical questionnaires. A 75-g OGTT was done in the morning. WHO criteria were used to classify the current diabetes status of study participants. RESULTS: Of the 1111 scheduled for the OGTT, 868 took the test; the participation rate was 77.8%. The prevalence of diabetes was 10.5 and 12.9%, and the prevalence of IGT was 14.7 and 18.0% for men and women, respectively. The prevalence of undiagnosed diabetes (4.9%) was almost equal to that of previously diagnosed diabetes (4.5%). CONCLUSIONS: The prevalence of diabetes in the Funagata area was two to four times higher than that of previous reports in Japan, in which many investigators used a urinary glucose test as a preliminary test. This difference is attributed to the method of determining the prevalence of diabetes. PMID- 8462381 TI - Glucose tolerance during and after pregnancy in nondiabetic women in an urban population in Tanzania. AB - OBJECTIVE: It is generally accepted that glucose tolerance deteriorates during pregnancy in the developed world. Several small studies have suggested that this may not be the case in sub-Saharan Africa. This study was designed to investigate changes in glucose tolerance in nondiabetic African women during pregnancy in Dar es Salaam, Tanzania. RESEARCH DESIGN AND METHODS: Women (n = 89) seen before the 14th wk of pregnancy without known diabetes were recruited: 58 had a 75-g OGTT in the 1st, 2nd, and 3rd trimesters and postpartum. RESULTS: Mean FBG levels were 3.9, 3.5, 3.6, and 3.7 mM in the 1st, 2nd, and 3rd trimesters and postpartum period, respectively. Values were significantly lower in the 2nd and 3rd trimesters than in the 1st and 2nd trimesters compared with postpartum. Mean 2-h blood glucoses were 4.7, 4.4, 4.3, and 4.2 mM, respectively. The 1st trimester value was significantly higher than in the 3rd trimester and postpartum. Fifteen (26%) of the 58 women showed a decreased or unchanged 2-h blood glucose during the course of pregnancy, 5 (9%) showed an increase, and no clear pattern was seen in 38 (67%). Values for fasting glucose showed similar trends. CONCLUSIONS: We conclude that women during pregnancy in an urban African setting show little change in glucose tolerance. This contrasts with women in both the developed world, where glucose tolerance worsens, and in a rural African environment, where glucose tends to improve. PMID- 8462382 TI - Exaggerated hyperglycemia after a pizza meal in well-controlled diabetes. AB - OBJECTIVE: To examine whether the postprandial hyperglycemic effect of pizza in well-controlled IDDM patients is related to overeating or to unique properties of this popular food. RESEARCH DESIGN AND METHODS: On two evenings, each patient (n = 8) consumed a meal that was similar in macronutrient composition except that one consisted of pizza and the other was a control meal that included high glycemic index foods. The insulin regimen was held constant. RESULTS: Postprandial glucose levels were within the target range (< or = 10 mM) after the control meal. Although the initial glucose increase was similar for the two meals, plasma glucose continued to rise and was significantly increased from 4 to 9 h after ingestion of pizza compared with the control meal (P < 0.05). This increase occurred even though free insulin, glucagon, and free fatty acid levels did not differ significantly. CONCLUSIONS: Our data suggest that pizza has properties that accentuate and sustain postprandial hyperglycemia. PMID- 8462384 TI - Effects of gemfibrozil on low-density lipoprotein particle size, density distribution, and composition in patients with type II diabetes. AB - OBJECTIVE: To study the effects of gemfibrozil treatment on LDL particle size, density distribution, and composition in NIDDM patients. RESEARCH DESIGN AND METHODS: We performed LDL analyses on 16 NIDDM patients with stable glycemic control. They were randomly allocated to receive either gemfibrozil (n = 8) or a placebo (n = 8) for 3 mo in a double-blind study. The LDL particle size distribution and the particle diameter of the major LDL peak were measured with nondenaturing polyacrylamide gradient gel electrophoresis. The density distribution and composition of LDL were determined with the density gradient ultracentrifugation method. RESULTS: In the gemfibrozil group the mean serum TG concentration decreased by 38%, HDL cholesterol concentration increased by 10%, and LDL cholesterol concentration by 17% (P < 0.05). During gemfibrozil therapy the mean particle diameter of the major LDL peak increased from 244 to 251 A (P < 0.05), whereas in the placebo group the mean LDL particle diameter remained unchanged. We found an inverse correlation between the changes of serum TG and the particle diameters of the major LDL peak (r = 0.85, P < 0.01). Gemfibrozil produced a shift in the LDL density distribution toward lower density. The mean peak density decreased from 1.0371 to 1.0345 g/ml because of a significant rise in the light LDL concentration from 141.0 to 183.2 mg/dl (P < 0.05), whereas the concentration of dense LDL had a tendency to decrease. In the placebo group the LDL density distribution did not change. Gemfibrozil increased the CE-to-TG ratio in LDL core lipids by 27% (P < 0.05); otherwise, the LDL composition was only slightly affected. CONCLUSIONS: The results indicate gemfibrozil-induced changes in LDL properties in NIDDM patients are similar to those previously reported in nondiabetic individuals and are related to changes in serum TG level. PMID- 8462383 TI - Sporting activity and hyperglycemia in middle-aged men. AB - OBJECTIVE: To assess the relationship between self-reported frequency of participation in sporting activity and the prevalence of hyperglycemia (nonfasting glucose level > or = 7.8 mM) in middle-aged men. RESEARCH DESIGN AND METHODS: We used a cross-sectional study of 7617 British middle-aged men, drawn from 24 general practices in England, Wales, and Scotland, who were participants in the British Regional Heart Study. The response rate was 78%. Patients with diabetes (physician-diagnosed) were excluded from our analysis. Frequency of participation in sporting activity was determined by the respondents and reported as none (61%), occasionally (12%), or frequently (27%). RESULTS: The age-adjusted prevalence odds ratio for hyperglycemia was 0.86 (95% confidence interval, 0.6 1.2) in those reporting occasional, and 0.62 (95% confidence interval, 0.4-0.85) in those reporting frequent sporting activity, compared with those reporting none. This effect of frequent sporting activity on the prevalence of hyperglycemia was independent of body mass index, occupational status, smoking status, systolic blood pressure, use of antihypertensive therapy, and time of sampling. CONCLUSIONS: Frequent sporting activity in middle-aged men is associated with a reduced prevalence of hyperglycemia and may reduce the risk of NIDDM. PMID- 8462385 TI - Development of impaired glucose tolerance with or without weight gain. AB - OBJECTIVE: To evaluate whether risk factors and changes in insulin concentrations differ in subjects who develop impaired glucose tolerance with or without weight gain. Hyperinsulinemia is a risk factor for impaired glucose tolerance, and insulin concentrations increase further with the development of impaired glucose tolerance. Its development, however, often is accompanied by weight gain, which, by itself, is associated with high insulin concentrations. RESEARCH DESIGN AND METHODS: Participants for this study were adult Pima Indians involved in an ongoing epidemiological study. Initially, all had normal glucose tolerance. During follow-up, 80 of 387 who did not gain weight developed impaired glucose tolerance, as did 295 of 1026 who gained weight. Risk factors for impaired glucose tolerance and the relationships between changes in weight and glucose and changes in insulin were evaluated by multivariate analyses. RESULTS: High baseline fasting insulin predicted impaired glucose tolerance regardless of weight after adjustment for age, sex, body mass index, and glucose. The development of impaired glucose tolerance was accompanied by a further increase in fasting and 2-h insulin, whether or not subjects gained weight. In both weight change groups, impaired glucose tolerance was associated with more centralized fat distribution. CONCLUSIONS: Fasting hyperinsulinemia, a reflection of insulin resistance, is associated with the risk of developing impaired glucose tolerance whether or not weight is gained. Impaired glucose tolerance occurs when insulin resistance increases further. Weight gain is the most common precipitating factor. Aging and physical inactivity are other possible precipitating factors. PMID- 8462386 TI - Renal function changes in microalbuminuric normotensive type II diabetic patients treated with angiotensin-converting enzyme inhibitors. AB - OBJECTIVE: To determine the effects of captopril on microalbuminuria and renal function in normotensive type II diabetic patients. RESEARCH DESIGN AND METHODS: A total of 26 patients were randomized in two homogeneous groups for clinical and analytical data in a 6-mo follow-up study. Group A received captopril (initial dose: 12.5 mg daily, increased according to tolerance); group B was untreated. RESULTS: Microalbuminuria decreased only in the treated group at 6 mo (P = 0.044) and a significant (P = 0.027) mean percentage change on microalbuminuria excretion between the groups was observed. Filtration fraction decreased in group A (baseline: 0.23 +/- 0.03; 6 mo: 0.22 +/- 0.04) and increased in group B (baseline: 0.22 +/- 0.04; 6 mo: 0.25 +/- 0.04) with a significant mean percentage change between the groups at 6 mo (P = 0.032). The mean percentage change in microalbuminuria was significantly correlated with a mean percentage change in diastolic blood pressure throughout the trial. Neither metabolic control nor sodium or protein intake changed in either group during the trial. CONCLUSIONS: These results suggest that captopril can help arrest microalbuminuria in normotensive type II diabetic patients, with a decrease in diastolic blood pressure and filtration fraction after a 6-mo treatment. PMID- 8462387 TI - The prevalence and identification of risk factors for NIDDM in urban Africans in Cape Town, South Africa. AB - OBJECTIVE: To determine the prevalence of NIDDM and associated risk factors in urban Africans in Cape Town, South Africa. RESEARCH DESIGN AND METHODS: With a three-stage, proportional, stratified, random cluster method, we sampled 1000 Africans, > 30 yr of age, living in African residential areas in Cape Town. We assessed glucose tolerance with a 75-g oral glucose tolerance test, according to World Health Organization criteria, and obtained anthropometric and demographic data. RESULTS: The response rate was 79%. The prevalence of NIDDM was 8.0% (confidence interval 5.8-10.3%), age-adjusted to world population figures and that of impaired glucose tolerance, 7.0% (confidence interval 4.9-9.1%). Multivariate analysis indicated that increased age (odds ratio 4.18), upper segment fat distribution (odds ratio 2.94), proportion of life spent in an urban area (odds ratio 2.32), and obesity (odds ratio 2.31) were significant independent risk factors for NIDDM. In contrast, sex, family history, alcohol intake, and physical activity were not independent risk factors. Only increased age (odds ratio 4.06) was a significant risk factor for impaired glucose tolerance. CONCLUSIONS: The prevalence of NIDDM in urban Africans in Cape Town, South Africa, is moderately high, and considerably higher than previous reports from Africa. The association of NIDDM with urbanization has important implications in view of the large-scale urbanization occurring in southern Africa. PMID- 8462388 TI - Insulinemia in children at low and high risk of NIDDM. AB - OBJECTIVE: Fasting hyperinsulinemia in the presence of normoglycemia usually indicates insulin resistance and is characteristic of populations at high risk for developing NIDDM. Hyperinsulinemia predicts the development of impaired glucose tolerance and NIDDM in Pima Indians, a population with a high incidence of NIDDM. Insulin concentrations in population-based samples of children who have different risks of developing NIDDM later in life have not been reported previously. RESEARCH DESIGN AND METHODS: We compared fasting insulin concentrations in two populations of nondiabetic children, 6-19 yr of age: Pima Indians from southern Arizona and Caucasians from Minnesota. RESULTS: Insulin concentration varied with age, sex, glucose concentration, and relative weight. Mean fasting insulin concentration was 140.3 pM in Pima Indian males, 94.4 pM in Caucasian males, 171.5 pM in Pima Indian females, and 107.1 pM in Caucasian females. For each sex, the mean fasting insulin concentration, controlled for age, glucose, and relative weight, was significantly higher in the Pima Indians than in the Caucasians (P < 0.001). CONCLUSIONS: From a young age, Pima Indian children have higher fasting insulin concentrations than Caucasian children. As hyperinsulinemia predicts subsequent NIDDM, these data suggest that the susceptibility to NIDDM is manifest at a young age as fasting hyperinsulinemia. PMID- 8462389 TI - Comparison of six commercial techniques in the measurement of microalbuminuria in diabetic patients. AB - OBJECTIVE: To evaluate the advantages and drawbacks of six commercially available techniques in the measurement of microalbuminuria in diabetic patients. RESEARCH DESIGN AND METHODS: Timed overnight urine samples from 75 patients in our diabetic clinic were tested with 2 qualitative tests (Micral-Test and Microbumintest) and assayed with 4 quantitative tests, which used different methodologies: double-antibody RIA, RID, IT, and NEPH. All tests were commercially available. The double-antibody RIA was taken as the golden standard. All urine samples were either negative or trace by Albustix (Ames, Elkhart, IN). Interobserver variation for the 2 qualitative tests was assessed by asking 12 experienced nurses to read the color changes on the dipsticks and the tablets simultaneously, using test solutions with albumin concentrations of 16, 32, and 64 mg/L. RESULTS: The 75 urine samples contained 0-154.2 mg/L of albumin. Correlation coefficients of RID, NEPH, and IT with RIA were 0.970, 0.975, and 0.974, respectively. Intra-assay and interassay CVs ranged from 1.36-11.5%. Microbumintest had a higher sensitivity (100 vs. 75%), but lower specificity (82.5 vs. 87.3%) than Micral-Test. Considerable interobserver variation existed in the matching of colors for both tests. Discrepancies were especially significant with Microbumintest, with 8 of 12 nurses misreading the 32 mg/L level. CONCLUSIONS: Correlations of the 3 quantitative methods with RIA were all > 0.970. Choice of test may depend more on considerations such as time, space, number of specimens to be handled, and availability of instruments. Both qualitative tests showed a relatively low specificity. Positive tests must be confirmed with quantitative assays before microalbuminuria is diagnosed. Microbumintest had a higher sensitivity, but its unacceptably high interobserver variation and lower specificity were serious drawbacks. PMID- 8462390 TI - Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. AB - OBJECTIVE: To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease. RESEARCH DESIGN AND METHODS: A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment. RESULTS: Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, -3.08 mM, 95% CI -4.12 to -2.04 mM, P < 0.0001) and MCR of glucose (median difference 0.40 ml.kg-1.min-1, interquartile range -0.10 to 1.30 ml.kg-1.min-1, P = 0.036). beta-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P < 0.001). Total triglyceride (median difference -0.2 mM, interquartile range -0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference -0.52 mM, 95% CI -0.83 to 0.22 mM, P = 0.002), and LDL cholesterol (mean difference -0.40 mM, 95% CI -0.64 to -0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference -5.3 AU/ml, 95% CI -8.2 to -2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference -2.4 micrograms/min, interquartile range -4.4 to -0.2 micrograms/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups. CONCLUSIONS: These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease. PMID- 8462391 TI - Pupillary abnormalities in type I diabetes occurring during adolescence. Comparisons with cardiovascular reflexes. AB - OBJECTIVE: To evaluate computerized infrared pupillometry for the assessment of autonomic neuropathy in adolescents with type I diabetes. RESEARCH DESIGN AND METHODS: We measured resting pupil diameters and pupillary light reflexes in 142 adolescents with type I diabetes (72 boys and 70 girls, 10.4-19.8 yr of age, duration of diabetes 0.7-18.3 yr) and in 75 nondiabetic control subjects (29 boys, 46 girls, 11.3-19.8 yr of age). All study participants were assessed using four standard cardiovascular tests: maximum-minimum heart rate during deep breathing (mean of three cycles); heart-rate change during a Valsalva maneuver (Valsalva ratio, mean of three maneuvers); lying-to-standing heart-rate change (30:15 ratio); and lying-to-standing BP change. RESULTS: Mean resting pupil diameters were significantly smaller in the diabetic group: 6.28 +/- 0.06 vs. 6.77 +/- 0.11 mm, P < 0.0001); and significantly smaller with greater duration of diabetes (r = -0.29, P = 0.0006) and higher levels of GHb (r = -0.24, P = 0.004). Patients with retinopathy grade 30 or more (Wisconsin 191 grading) had significantly smaller resting pupil diameters: 5.9 +/- 0.16 vs. 6.4 +/- 0.12 mm, P = 0.008). The phasic light reflex as determined by reflex amplitude and maximum constriction velocity was significantly reduced in the diabetic group: 2.27 +/- 0.03 vs. 2.44 +/- 0.04 mm, P = 0.0009; and 6.68 +/- 0.12 vs. 7.24 +/- 0.16 mm/s, P = 0.007). Reduced reflex amplitude was related to a longer postpubertal duration of diabetes (r = -0.18, P = 0.04). We found no association between pupillary and cardiovascular tests. CONCLUSIONS: Infrared computerized pupillometry demonstrates subclinical diabetic autonomic neuropathy as early as adolescence. Its presence seems to be related to longer duration of diabetes and unfavorable metabolic control. PMID- 8462392 TI - Microalbuminuria in NIDDM. AB - OBJECTIVE: To determine an effective screening procedure for microalbuminuria. RESEARCH DESIGN AND METHODS: The prevalence of microalbuminuria in NIDDM patients whose urine was negative on routine Albustix testing was studied. Microalbuminuria was measured in overnight urine samples from 128 NIDDM patients on at least two of three occasions over a 6-mo period. Patients were tested with Micro-Bumintest or Micral-Test. RESULTS: Ten of 128 patients had albumin concentrations > or = 20 mg/L on two or more occasions, 14 patients had A-C ratios > or = 3 mg/M on two or more occasions, and 9 patients had both. CONCLUSIONS: Neither Micro-Bumintest nor Micral-Test is a useful or feasible screening procedure for microalbuminuria. PMID- 8462393 TI - Maternal age and birth order of young IDDM patients. A study from southern India. AB - OBJECTIVE: To assess the effects of maternal age and birth order on the risk of IDDM in Asian Indians. RESEARCH DESIGN AND METHODS: Data from a diabetes registry in Madras, India, was used to find IDDM patients diagnosed before 20 yr of age. A questionnaire was used to elicit clinical details of subjects. RESULTS: Children with mothers < or = 24 yr of age had a higher percentage of IDDM. Children with lower birth orders had a higher prevalence of IDDM. CONCLUSIONS: The risk of IDDM in children is increased in children with lower birth orders, born of younger mothers. PMID- 8462394 TI - Oral health in patients with type II diabetes and impaired glucose tolerance. AB - OBJECTIVE: To assess the influence of type II diabetes and impaired glucose tolerance on dental, periodontal, and oral mucosal tissues. RESEARCH DESIGN AND METHODS: We examined 11 subjects with type II diabetes, 32 with impaired glucose tolerance, and 43 control subjects from the oral physiology component of the Baltimore Longitudinal Study of Aging. At the time of the study, none of the participants was taking medication nor being treated for any medical problems other than diabetes. RESULTS: Only a few statistically significant dental and periodontal changes were apparent in the group with type II diabetes, and no oral mucosal differences existed between the diabetes and control groups. Dental, periodontal, and oral mucosal parameters in patients with impaired glucose tolerance were essentially indistinguishable from the other two groups. CONCLUSIONS: These findings suggest that among well-controlled individuals with type II diabetes and impaired glucose tolerance, few appreciable differences are evident in oral health. PMID- 8462395 TI - Undiagnosed NIDDM: clinical and public health issues. PMID- 8462396 TI - Is it time to introduce metformin in the U.S.? PMID- 8462397 TI - Patient outcomes research and type II diabetes. The Agency for Health Care Policy and Research focuses on improving patient outcomes. PMID- 8462398 TI - Sensory threshold testing. PMID- 8462399 TI - Diabetes in the east African islands of Zanzibar. PMID- 8462400 TI - Micral-test. A new semiquantitative test for urinary albumin. PMID- 8462401 TI - Time for a change. PMID- 8462402 TI - Diabetic ketoacidosis in pregnancy. Another atypical case. PMID- 8462403 TI - Renal failure in Wolfram's syndrome. PMID- 8462404 TI - Lipid and lipoprotein levels in young IDDM patients. PMID- 8462405 TI - Stability of mailed and couriered capillary HbA1c samples. PMID- 8462406 TI - Comment on consistency. PMID- 8462407 TI - With federal funding ban lifted, fetal tissue research will continue in earnest. PMID- 8462408 TI - Proposed FHWA regulations for insulin-using commercial motor vehicle operators. PMID- 8462409 TI - Hodgkin's disease and the malignant lymphomas. AB - The unanticipated finding of a subcutaneous swelling, typically an enlarged lymph node in the neck, is legitimate cause for concern. After excluding benign or reactive conditions, this sign should initiate a series of investigations to characterize the neoplasm and, in the case of a lymphoma, lead to prompt treatment aimed at cure. The classic description of such cervical adenopathy is that by Thomas Hodgkin, who clearly recorded both the clinical behavior and the macroscopic findings evident at dissection. Subsequent histologic study revealed the multinucleate giant cells that characterize the tumor that now bears his name and linked it to those of Greenfield, Sternberg, and Reed. Initial debate centered on whether this entity was inflammatory or malignant, with the issue further clouded by the frequent coexistence of tuberculosis. Although a number of features exist in favor of both concepts, current consensus places it among the neoplastic processes. Hodgkin's disease was separated from other malignant lymphomas as agreement on diagnostic criteria emerged. The next major step forward was the demonstration, first by Vera Peters and then by Henry Kaplan, that adequate doses of radiotherapy were curative when delivered to treatment fields that encompassed the tumor. A further milestone was the introduction by Vincent DeVita, Jr., and his colleagues of combination chemotherapy that was effective in late stage of disseminated disease. The established cornerstones of managing these patients are accurate diagnosis; precise anatomic staging, modified as appropriate by associated factors known to have prognostic value; and selection of irradiation, chemotherapy, or whatever combination will result in the best possible patient survival. However, success is not universal, and death due to resistant or relapsing disease is encountered all too frequently. It is here that the benefits of a multidisciplinary approach are evident, because a substantial level of expertise coupled with sound judgment is needed to salvage these individuals, often by means of investigational programs. Some of the latter are limited by profound myelosuppression, and safety may center on the use of cytokines in the form of interleukins and growth factors, with or without bone marrow transplantation. In such situations, benefit must be balanced against risks in well-structured clinical trials that embody informed consent. Herein lies one of the major goals for the next decade. The non-Hodgkin's lymphomas can conveniently be considered in two broad categories. Some follow an indolent clinical course, in which the lymph node retains a follicular pattern with small component cells, and others are aggressive tumors, in which primitive blasts have diffusely effaced the glandular architecture.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8462410 TI - Punishing pregnant drug users: enhancing the flight from care. AB - One hundred forty-two low income women were interviewed postpartum to determine their attitudes regarding the potential effects of a punitive law on the behavior of substance-using pregnant women. The convenience sample was primarily black (85.2%) and single (81%) and 14.8% admitted use of illicit drugs during pregnancy. A goodness-of-fit chi-square analysis revealed that subjects believed a punitive law would be a significant deterrent to substance-using gravida seeking prenatal care, drug testing or drug treatment (P < 0.01). Comments indicated that substance-using pregnant women would 'go underground' to avoid detection and treatment for fear of incarceration and loss of their children. PMID- 8462411 TI - Restricting the availability of alcohol and rates of personal violence (suicide and homicide). PMID- 8462412 TI - International Cannabis Research Society meeting summary, Keystone, CO (June 19 20, 1992). PMID- 8462413 TI - Buprenorphine and cocaine effects on social behavior of monkeys. AB - We administered for 2 weeks intramuscular buprenorphine 0.3 mg/kg per day (and in a separate series, its vehicle) to each of 7 male, group-living Macaca fuscata (Japanese Snow Monkeys). Animals received one injection of cocaine 0.75 mg/kg and one of saline (about Days 9 and 14) in each series; after each of these doses ethologic observers recorded for 3 h the frequency of occurrence of 64 separate social, self-care, position and other behaviors. Cocaine alone changed the frequency of many behaviors. Buprenorphine alone only reduced the frequency of eating, yawning and ejaculation. The drugs had no interactive effects on behavior. In a dose reported to suppress monkeys' heroin and cocaine self administration, buprenorphine showed remarkably few disruptions of normal group behavior. But it neither reversed nor enhanced cocaine's behavioral effects. PMID- 8462414 TI - Enhancement of cocaine-induced hepatotoxicity by ethanol. AB - The contribution of moderate ethanol consumption on cocaine induced hepatotoxicity and the role lipid peroxidation plays as a possible mechanism of such increased hepatotoxicity were evaluated. Male C57BL/6 mice were injected interperitoneally (i.p.) with increasing doses of cocaine, from 10 to 50 mg/kg body weight daily and simultaneously fed a liquid diet containing 28% of the calories as ethanol for 5 or 9 weeks. Control mice received saline (i.p.) and an isocaloric carbohydrate diet. Lipid fluorescence and conjugated dienes of extracted lipids and amounts of malondialdehyde (MDA) were evaluated as indices of lipoperoxidation. In addition, serum alanine aminotransferase and aspartate transaminase were measured as indicators of liver injury and cellular death. After 9 weeks, ethanol consumption during cocaine treatment increased hepatic lipid fluorescence, conjugated dienes and MDA about twofold over mice-treated with cocaine alone. Similarly, serum transaminases were 2.8-6-fold greater in mice consuming alcohol and treated with cocaine than in mice treated with cocaine only. Histological examination of livers from mice fed ethanol during treatment with cocaine exhibited increased hepatic injuries and necrosis. The data suggest that ethanol exacerbates cocaine-induced hepatotoxicity via increases in free radical activity and hepatic lipid peroxidation. PMID- 8462415 TI - Reinforcing effects of extended inhalation of nitrous oxide in humans. AB - The subjective, psychomotor and reinforcing effects of nitrous oxide at subanesthetic doses (30% and 40% in oxygen) were determined in normal healthy volunteers using a choice paradigm. Thirty percent nitrous oxide was chosen no more often than oxygen (41.6% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was no more reinforcing than oxygen inhalation. Forty percent nitrous oxide was chosen significantly less often than oxygen (22% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was less reinforcing than oxygen. Nitrous oxide produced robust subjective effects (e.g., increased ratings of 'high,' 'tingling,' and 'dizzy'). Subjects who chose nitrous oxide reported pleasant subjective effects and liked it, while those who chose placebo reported unpleasant subjective effects and disliked it. Both concentrations of nitrous oxide impaired psychomotor performance in all subjects. The lack of reinforcing effects noted in the present study, given nitrous oxide's known abuse potential, is discussed. PMID- 8462416 TI - Cocaine use and other suspected risk factors for obsessive-compulsive disorder: a prospective study with data from the Epidemiologic Catchment Area surveys. AB - Using prospectively gathered epidemiologic data, we sought to estimate the degree to which the risk of obsessive-compulsive disorder might be elevated among adults actively using cocaine, with and without illicit use of marijuana or other controlled substances. Study subjects were selected in 1980-84 by taking probability samples of adult household residents at five sites of the Epidemiologic Catchment Area (ECA) Program: New Haven, Connecticut; Baltimore, Maryland; St. Louis, Missouri; Durham-Piedmont, North Carolina; Los Angeles, California. Soon after sampling at baseline, a total of 18,572 participants completed standardized interviews to measure suspected risk factors (including illicit drug use) and to evaluate whether they had met diagnostic criteria for currently or formerly active obsessive-compulsive disorder (OCD), as well as other mental disorders. The interviews were re-administered 1 year later to identify incident cases among 13,306 at-risk participants, 414 being active cocaine users. After sorting these participants into strata defined by age and census tract of household residence and after excluding persons found at baseline to have active or prior OCD, we found 105 incident cases of OCD within 103 of the age-matched and residence-matched strata, which also contained a total of 514 subjects who had not developed OCD. Applying standard epidemiologic strategies presented in prior ECA research reports, we performed conditional multiple logistic regression to estimate the risk of OCD for active cocaine users versus non-users. We also performed unconditional multiple logistic regression to estimate OCD risk for the 414 active cocaine users versus the 12,892 participants not using cocaine. Both of these epidemiologic strategies yielded consistent results: subjects actively using cocaine and also marijuana were found to be at increased risk for OCD. Under the conditional model, the estimated relative risk was 7.2 (P = 0.03), while the value from unconditional regression was 4.1 (P = 0.01). Active users of cocaine almost always were active users of marijuana or some other controlled substance, so it was not possible to estimate a relative risk value for subjects using cocaine only. Nonetheless, if replicated, this epidemiologic test of the cocaine-OCD hypothesis warrants attention in laboratory and clinical research, as do other suspected risk factors identified in the study, including sex (being female), employment status (not working for pay) and a prior history of distinct psychiatric disorders such as alcohol dependence, affective disorders and phobic disorders. PMID- 8462417 TI - [Origin and development of the animal welfare law]. AB - At July 2, 1969, the Deutsche Bundestag has invited the Bundesregierung to submit a new and comprehensive law for animal welfare. After having removed difficulties with the constitution by completion of the constitution (at 18. March 1971) with animal welfare an outline of a new animal welfare law was presented to the Deutsche Bundestag in September 1971, and at July 24., 1972, the new law came into force. The leading idea of the former right, to protect the animal against pain and suffering has been promoted and extended to the protection of life of the animal simply. The animals protection-position is only allowed to restrict, if there is a reasonable proof coming out from very important common interests. The law prescribes for those, who are holders of animal more duties than in former time; species and needs of animal are to be laid down. To avoid the excavation of prohibition of experiments with animal by many exceptions the principle is introduced to approve respectively to notify experiments with animals before beginning. The amendment of the animal welfare law of August 12, 1986, concerns especially the regulations about experiments with animals, among many other new instructions a commission for ethics has been introduced. New is also, that the importance of animals as fellow-creature is mentioned in the law. The social process of learning in animal welfare is not yet finished, the new animal welfare law has given a contribution for arising a responsibility for ethics in a capable of bearing. PMID- 8462418 TI - [Are amendments to the German animal welfare law necessary?]. AB - The author gives a survey on the actual discussions and negotiations to amend the German Animal Welfare Act. Additionally, he reports about preparations to amend existing and to implement new animal welfare regulations. PMID- 8462419 TI - [Limits of infinite animal welfare in the internal market of the European community]. AB - The European Communities are, above all, economically oriented. Thus, as animal protection is concerned, EC legislation is only realized to an amount that ensures a smooth functioning of the internal market. In this sense, animal protection with in EC finds its limits in the Treaty of Rome rather than could be called "borderless". Nevertheless, a deterioration of the now existing level of animal protection in the Federal Republic of Germany should not be feared due to increasing European integration. Every member state still has the prerogative to issue more strict regulations than the minimum requirements of the EC. PMID- 8462420 TI - [Duties of the Central Office for Documentation and Evaluation of Alternative and Supplementary Methods for Animal Experimentation at the Institute for Veterinary Medicine of the Federal Health Office, Berlin]. AB - A National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments (ZEBET) was established at the Department of Veterinary Medicine of the German Federal Health Office (BGA) in 1989. It is supporting wherever possible the basic principles of animal protection: to replace animal experiments, to reduce the number of laboratory animals in experiments, and to reduce the suffering of those animals used in experiments. ZEBET is responsible for documentation of and information on alternative methods to animal experiments. ZEBET is also the national center for planning, funding and coordinating validation programs for alternative test methods and has laboratory facilities for developing new experimental approaches. PMID- 8462421 TI - [The use of the organs of slaughtered animals for the testing of drugs: suitability of the bovine udder for the study of substances active through the skin]. AB - Various in vitro models are used to study the transdermal penetration and absorption of test compounds. The isolated perfused bovine udder is described as a new in vitro model. Using bovine udders from slaughtered healthy cows, the percutaneous absorption of dexamethasone, benzoyl peroxide and isosorbide dinitrate was measured. For further validation of the described model, additional studies are necessary. PMID- 8462422 TI - [Handling of animals for slaughter according to animal welfare regulations]. AB - According to animal protection the transport and proceeding of slaughtering are a difficult topic to cope with. The section of people is often restricted to distrust and rejection. In order to achieve improvement we need laws which prescribe the transport standards in particular with regard to the duration of driving and resting periods and the feeding. Transports which exceed 12 h enlarge the risk of disregarding laws and prescriptions and should on principle be prohibited. At least the important coherence between protection of slaughter animals on the one hand and the meat quality on the other hand requires a careful treatment of the animals from the producer to the slaughtering. The only successful options are strict control and high penalties. To get the method of narcosis of pigs out of common criticism we should lead our minds into a new direction: In this case animal protection should be more reflected to than meat hygiene problems and therefore the possibility of a provoked heart failure before the bleeding out should be realized. PMID- 8462423 TI - [Experiences with the supervision of electric stunning of slaughter swine and the technical evaluation of stunning equipment in the government district of Weser Ems]. AB - The performance of electrical stunning in abattoirs is being investigated with regard to animal welfare. The results emphasize the necessity of appropriate training for all persons involved with the stunning and slaughter of livestock. The discussion includes problems associated with stunning. References are made to technical equipment used for monitoring electrical stunning and personal safety precautions. PMID- 8462424 TI - [Raising dogs and cats in compliance with animal welfare using advice on behavior and behavior therapy]. AB - Housing conditions of companion animals are often not adequate to animal welfare. This is caused by a generally negative attitude towards animals in the public, combined with a lack of knowledge about the normal behaviour and the animals demands towards their environment. In the interest of animal welfare, measures are needed which could help to improve the attitude towards animals by the general public. A further aim should be to provide a better knowledge about the needs of animals in the group of persons owning animals as well as persons planning to buy one in the future. Essential improvements in the housing conditions of dogs and cats can be expected by a more intense engagement of veterinarians in behaviour therapy. Individual points of this thematic will be discussed, suggestions as well as advice for the improvement of work will be introduced. PMID- 8462425 TI - [Pain and fear in animals]. AB - Pain and fear are feelings of reluctance, which result in a behaviour of avoidance. They are protective mechanisms and are only partly approachable to the quantification with natural scientific methods. It will pointed to the central role of the diencephalon, limbic system and the cerebral cortex concerning the processing and valuation of mental state. The recognition of clinical symptoms and precise behavioural observations are an essential aid to assess the state of pain and fear in animals. PMID- 8462426 TI - [Animal welfare standards in ecological animal husbandry and the possibilities of their regulation]. AB - There is an ethic claim to an increasing consideration of animal welfare in agricultural husbandry. To put this in practise requires the consumer's willingness to pay higher prices for food, produced according to animal's needs. A growing number of consumers is willing to do that. For the higher price the consumer expects a product-security, which guarantees processing standards by transparent criteria and inspection. Guidelines in organic agriculture regulate standards of animal welfare and environmental friendly production. Standards of animal welfare are far beyond those in protection of animals legislation. Nevertheless, they don't allow a general judgement about animal welfare in husbandry systems on organic ruled farms. A practicable and conclusive valuation concept is necessary. It is referred to the animal needs index as a concept for valuation, which is already tested in practice. PMID- 8462427 TI - [The problems of making birds unable to fly and questions of raising waterfowl in ponds from the viewpoint of animal welfare]. AB - From the viewpoint of the current law on animal welfare, the methods of rendering birds flightless are described and evaluated. Besides the animal welfare, other law statutes are to be paid attention to obligatory when waterfowl is kept on ponds. The raising and fattening of ducks and geese without water to swim on, can also be advocated from the angle of animal welfare. PMID- 8462428 TI - [Problems relevant to animal welfare in the control of pet shops from the viewpoint of official veterinarians]. AB - Results of an inquiry of all official veterinarians in Berlin are presented, concerning the situation of animal welfare in pet shops. Typical problems of keeping animals in pet shops are revealed. Many of the official veterinarians make complaints about the lack of practical guidelines, manuals or expert opinions when they are asked to give legal assessments. Existing recommendations, e.g. for cage sizes, are of a broad variety, which is underlined by some demonstrative pictures. PMID- 8462429 TI - [Legal protection of industry and animal welfare--legal and ethical problems]. AB - The first animal patent for the so called "Harvard-onco-mouse" has been widely discussed in the media and in public respectively. The opinion of veterinarians on animal patents should be based as far as possible on objective information, such as the legal situation and consideration of ethical discussion. The paper contains information on the following subjects: definition, aim and purpose of patents, patentability of microorganisms and genes, animal patents, animal rights and patents, ethics and animal patents. PMID- 8462430 TI - A multicenter randomized trial of high frequency oscillatory ventilation as compared with conventional mechanical ventilation in preterm infants with respiratory failure. AB - A multicenter randomised trial was conducted in nine neonatal centers in Japan to re-evaluate the safety and the efficacy of high frequency oscillatory ventilation using the piston type oscillator (Hummingbird) in the treatment of respiratory failure in preterm infants weighing between 750 and 2000 g at birth. A total of 92 infants were enrolled in the study. Forty-six infants were allocated to high frequency oscillatory ventilation and 46 infants to conventional mechanical ventilation. There were no differences in sex, birth weight, gestation and Apgar score between groups. The study was begun 2.0 +/- 1.6 h (mean +/- S.D.) after birth in the high frequency oscillation group and 1.7 +/- 1.5 h after birth in the conventional mechanical ventilation group. The absence of intraventricular hemorrhage was confirmed by echography in all cases before beginning ventilation. Mortality was similar in high frequency oscillatory ventilation and conventional mechanical ventilation (0 and 2%). The incidence of intraventricular hemorrhage was also similar in the high frequency and conventional mechanical ventilation groups (15 and 13% overall; 4 and 2% in grades III and IV, respectively). Nine percent of the infants in high frequency oscillatory ventilation and 13% in conventional mechanical ventilation developed bronchopulmonary dysplasia, but the difference was not significant. The frequency of air leaks was also equal in both groups. Periventricular leukomalacia was detected in 9% of infants on conventional mechanical ventilation and 2% on high frequency oscillation, but the difference was not significant. Mean airway pressure was significantly higher in the high frequency oscillatory ventilation group and the infants on high frequency oscillation showed a significantly higher arterial to alveolar oxygen tension ratio after 6 h of treatment. These results suggest that high frequency oscillatory ventilation does not increase the risk of severe complications such as air leaks, intraventricular hemorrhage or periventricular leukomalacia when it is used by experienced neonatologists. Indeed high frequency oscillatory ventilation helps provide better oxygenation with higher mean airway pressure without increasing the risk of bronchopulmonary dysplasia and severe complications such as air leaks and intraventricular hemorrhage. PMID- 8462431 TI - Development of ultradian rhythm of EEG activities in premature babies. AB - Ultradian rhythms in electroencephalogram (EEG) activity in premature neonates were studied. The values of square roots of total power (SQP) of EEG showed a normal Gaussian distribution. We analyzed the smoothed time series of SQP by autoregressive analysis and component analysis. Ultradian rhythm was divided into four groups by period length (group I: 5-30 min, group II: 30-60 min, group III: 60-100 min, group IV: longer than 100 min). Group IV rhythms were not detected before 32 weeks of gestation. Changes in the characteristic values of ultradian components in group II showed that there were critical periods in the development of central nervous activity at 29 and 33 weeks of gestation. This method allowed detection of ultradian rhythms, even at very early gestation, directly from the neonatal central nervous system. This method may be applicable to ill infants. PMID- 8462432 TI - Patterns of development in fetal breathing activity in the latter third of gestation of the baboon. AB - Patterns of fetal breathing activity were examined in a longitudinal study of the fetal baboon over the latter third of gestation. More than 1400 h of recorded tracheal fluid pressure in 16 or 24 h records from seven fetuses over a range in gestation from 121 to 172 days (term, 175-180 days) were analyzed. In these 81 records, there was a high degree of variability in the percent of time spent breathing by the fetuses (range, 14-83%) with no apparent influence of gestational age (mean +/- S.D., 45.6 +/- 17.6%). Nonetheless, the mean amplitude of fetal breaths increased with gestation from absolute values of about 5-10 mmHg (r = 0.73, P < 0.001) and the mean inspiratory time interval increased from about 0.45-0.55 s (r = 0.40, P < 0.001). During epochs of breathing, the mean rate decreased from about 42-36 breaths per min (r = -0.54, P < 0.001) and the indices of both short term (r = -0.54, P < 0.001) and long term (r = -0.73, P < 0.001) variability in rate decreased. These results demonstrate a clearly defined pattern of development in the breathing activity of the fetal baboon which is comparable to the pattern described for the human fetus in the third trimester of gestation. These similarities suggest that the progressive functional maturation of the mechanisms generating respiratory patterns are comparable among primate species. PMID- 8462433 TI - Characterization of the neonatal heart rate baroreflex during and after ECMO. AB - Prolonged continuous blood pressure (BP) and heart rate (HR) recordings from neonates of 35 to 42 weeks gestation were studied during and after ECMO. Data segments with significant deviation of BP were extracted for further analysis. The simultaneous changes in BP and HR were compared and the slope of the regression determined baroreflex sensitivity (BRS). Of 464 BP deviations, 98% produced curves with a negative slope consistent with the presence of a baroreflex. The average BRS was -1.0 +/- 0.8 bpm/mmHg (mean +/- S.D.) and curves were steeper during rising BP than falling BP (-1.1 +/- 0.9 beats/min per mmHg versus -0.9 +/- 0.6, P = 0.001). The baroreflex was more sensitive during ECMO than after ECMO to both rising BP (-1.0 +/- 0.5 beats/min per mmHg versus -0.7 +/ 0.5, P = 0.004) and falling BP (-1.0 +/- 0.6 beats/min/mmHg versus -0.7 +/- 0.5, P = 0.04). HR response curves obtained during different BP fluctuations on the same recording had varying threshold, consistent with acute resetting. One infant demonstrated chronic baroreceptor resetting over 3 days to a rise in resting BP. The near-term, critically ill neonate has an active baroreflex which is capable of resetting. ECMO was associated with accentuation of the baroreflex response. PMID- 8462434 TI - Qualitative abnormal fetal breathing movements, associated with tracheal atresia. AB - A case is reported in which qualitatively, grossly abnormal fetal breathing movements turned out to be indicative of complete tracheal atresia. Fetal breathing movements were vigorous and jerky and of large amplitude; similarly abnormal movements were observed after birth. At postmortem tracheal atresia was diagnosed, in combination with other congenital abnormalities, which pointed to a VATER-association. The combination of a VATER-association with tracheal atresia has only been reported once before. An absence of the normal Hering-Breuer reflex in this case of complete tracheal atresia, probably explains the abnormal fetal breathing pattern. This case is in line with a growing number of reports in literature in which qualitatively abnormal fetal movements were indicative of congenital malformations. PMID- 8462435 TI - Plasma amino acid profiles in preterm infants receiving Vamin 9 glucose or Vamin infant. AB - Amino acid profiles were measured in 29 low-birth-weight infants receiving either Vamin 9 glucose (n = 18, group A) or Vamin Infant (n = 11, group B) as the amino acid source in parenteral nutrition; intake was otherwise identical. Infants were sampled when receiving 430 mgN/kg per day (3.2 g/kg per day amino acids) and 90 non-protein kcal/kg per day. There was no difference between groups in birth weight, gestational or postnatal age. The percentage N retention was similar in both (68 and 60%, groups A and B respectively). Phenylalanine and tyrosine levels were higher in those who received Vamin 9 glucose but 55% of infants given Vamin Infant had tyrosine levels below the lower limit of the target range. Cysteine levels were low in both groups. Further modification of the amino acid composition of parenteral solutions for the newborn is necessary. If sufficient non-protein energy can be provided the risk of abnormally high amino acid levels is reduced. PMID- 8462436 TI - [Colombia: evaluation of the masters degree in nursing, Universidad del Valle 1988-1990]. PMID- 8462437 TI - [Peru: health promotion/pesticide use. Reflections on an instructional course for farmers]. PMID- 8462438 TI - [Development of human resources for the local health systems: Brazil]. PMID- 8462439 TI - [Health personnel and work: a glance at the institutions]. PMID- 8462440 TI - [Participation and partnership in health]. PMID- 8462441 TI - [Proposal for a model for the study and development of intersectorial action in health]. PMID- 8462442 TI - [Strategic administration of the development of human resources in health systems]. PMID- 8462443 TI - [Venezuela: health concepts and practices among inhabitants of suburban communities and their health agents]. PMID- 8462444 TI - Insulin and insulin-like growth factor I receptors: are there functional distinctions? PMID- 8462445 TI - Differential posttranslational processing of proenkephalin in rat bone marrow and spleen mononuclear cells: evidence for synenkephalin cleavage. AB - Proenkephalin (PENK) messenger RNA was reported to be present in bone marrow mononuclear cells (BMMC) and spleen mononuclear cells (SMC). Nevertheless, the pattern of PENK products in normal cells of the rat immune system, which is important for defining the physiological role of PENK gene expression, has not been well established. In this work we have characterized the processing of the opioid portion (met-enkephalin-containing peptides) and nonopioid portion (synenkephalin-derived peptides) of PENK in rat BMMC and SMC. Met-enkephalin containing peptides were detected in mononuclear cells of both hematopoietic tissues. In BMMC, free immunoreactive (IR)-met-enkephalin corresponded only to the 15% of total met-enkephalin-IR, whereas in SMC it represented the 66.5%. Gel filtration chromatography showed that BMMC contained partially processed PENK derived peptides of high and intermediate molecular weight, whereas SMC displayed fully processed products containing met-enkephalin and/or the carboxyterminal portion of synenkephalin. HPLC purification of low molecular weight products showed that free IR-met-enkephalin in SMC mainly corresponded to met-enkephalin and oxidized met-enkephalin. In addition we have characterized in SMC three peptides lower than 3.0 kilodalton containing the C-terminal sequence of synenkephalin. These peptides were purified by gel filtration, affinity chromatography, ion exchange chromatography, and HPLC. These results show that PENK was processed in mononuclear cells of the primary (bone marrow) and secondary (spleen) organs of the rat hematopoietic system, as occurs in neural and endocrine tissues. Nevertheless, the precursor was cleaved only in the latter tissue to low molecular weight peptides. Furthermore we demonstrated that synenkephalin (proenkephalin 1-70) in SMC was processed to low molecular weight peptides containing the C-terminus free. This last result suggests that a dibasic Lys-Lys and monobasic (Lys) sites were cleaved. PMID- 8462446 TI - A truncated human insulin receptor missing the COOH-terminal 365 amino acid residues does not undergo insulin-mediated receptor migration or aggregation. AB - A previous study of tyrosine kinase-defective insulin receptors demonstrated that receptor autophosphorylation or tyrosine kinase activity was required for concentrating insulin receptors in coated pits, but not for their migration or aggregation on the cell surface. Furthermore, receptor migration and aggregation on the cell surface were not sufficient to cause internalization of the occupied receptors in coated pits. In the present study, biochemical and ultrastructural techniques were used to compare insulin receptor mobility and internalization in Rat 1 fibroblasts expressing wild-type human insulin receptors (HIRc) with those in cells expressing receptors truncated at residues 978 (HIR delta 978) or 1301 of the carboxyl-terminus (HIR delta CT). There were no significant differences in the mobility or internalization of insulin receptors on HIR delta CT cells compared to those of insulin receptors on HIRc cells. Ultrastructural analysis revealed that truncated insulin receptors on HIR delta 978 cells failed to migrate from their initial location on the microvilli, move to the plasma membrane, and aggregate in coated pits. Receptor-mediated insulin internalization in HIR delta 978 cells was markedly decreased due entirely to a decrease in ATP dependent, coated pit-mediated internalization. ATP-independent endocytosis in non-coated pinocytotic invaginations was not affected by receptor truncations. These results provide evidence of the roles that regions of the beta-subunit play in the processing of occupied insulin receptors. 1) The carboxyl-terminus of the insulin receptor is not involved in the events leading to receptor internalization, i.e. migration, aggregation, and concentration in coated pits. 2) Internalization of insulin receptors by the ATP-independent noncoated invagination pathway is not regulated by residues in the insulin receptor beta subunit distal to 978. 3) Sequences in the beta-subunit between 978-1300, but not the autophosphorylation and kinase domains, are involved in insulin-induced receptor migration and aggregation. PMID- 8462447 TI - Effects of age and endogenously secreted human growth hormone on the regulation of gonadotropin secretion in female and male transgenic mice expressing the human growth hormone gene. AB - In aging rats and humans, GH secretion is reduced. In transgenic mice bearing the human (h) GH gene, hGH is secreted during the entire lifespan. To evaluate the effects of endogenously secreted hGH on age-related changes in hypothalamic pituitary function, the following two experiments were conducted in young (2.5-4 months of age) and old (11-14 months of age) female and male transgenic mice expressing the hGH gene and their normal siblings. In Exp I, young and old female transgenic mice and their normal siblings were ovariectomized. On days 8 and 9 after ovariectomy, mice were injected (sc) with oil or primed with 0.5 micrograms estradiol benzoate (EB) in oil, 24 h later treated with 10 micrograms EB/100 g BW, and a day later bled for the determination of FSH, LH, PRL, and hGH levels by RIAs. In Exp II, young and old male transgenic mice and their normal littermates were castrated and injected with either peanut oil or testosterone propionate (TP; 1 microgram/g BW) in oil. Blood samples were obtained 18-20 h after oil or TP injection. Plasma FSH, LH, PRL, and hGH levels were measured by RIAs. hGH was present in the circulation of young and old transgenic mice, but not in normal siblings. Circulating FSH and LH levels were significantly lower in ovariectomized young and old transgenic mice than in similarly treated young and old normal siblings. The suppressive effect of EB on LH secretion was reduced in ovary-ablated young and old transgenic mice. The PRL response to EB treatment was increased (P < 0.005) in old ovariectomized transgenic mice. In the male, the castration-induced increase in plasma LH levels was higher (P < 0.05) in young transgenic mice. Administration of TP failed to suppress the absolute plasma LH levels in castrated young and old transgenic mice. However, the percent decrease in circulating LH levels was lower in young and old transgenic mice. The castration-induced increase in FSH secretion was reduced (P < 0.005) in aged transgenic mice. The effects of TP on plasma FSH levels were similar to its effects on LH secretion. Gonad-ablated young and old transgenic mice of both sexes are hypoprolactinemic. These observations demonstrate that endogenously secreted hGH modulates gonadotropin and PRL secretion in young and old mice bearing the hGH gene and indicate that the changes in the hypothalamic-pituitary system of mice expressing the hGH gene are similar to those observed in aging human subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8462448 TI - Reciprocal modulation of interleukin-1 beta (IL-1 beta) and IL-1 receptors by lipopolysaccharide (endotoxin) treatment in the mouse brain-endocrine-immune axis. AB - The cytokine interleukin-1 (IL-1) alters a variety of immune, central nervous system, and neuroendocrine activities characteristic of an integrator of the brain-endocrine-immune response to stress. In an attempt to define the regulation of IL-1 and IL-1 receptors in the mouse brain-endocrine-immune axis, we measured tissue levels of IL-1 beta using an enzyme-linked immunosorbent assay and iodine 125-labeled recombinant human IL-1 alpha ([125I]IL-1 alpha) binding in hippocampus, hypothalamus, pituitary, epididymus, testis, and spleen after ip injection of the bacterial endotoxin lipopolysaccharide (LPS). Basal IL-1 beta levels were detectable in all of the tissues examined. IL-1 beta levels were dramatically increased in the peripheral tissues (pituitary, testis, and spleen) 2-6 h after a single LPS injection; however, no significant changes were observed in the brain (hippocampus and hypothalamus). [125I]IL-1 alpha binding was decreased in the spleen, but was unchanged in the hippocampus and testis after a single LPS injection. To determine whether activation of IL-1 in brain may require more sustained exposure to endotoxin, we examined the effects of two injections of LPS at 0 and 12 h. After two LPS injections (0 and 12 h), significant increases in IL-1 beta concentrations were noted in the hippocampus, hypothalamus, spleen, testis and epididymus; [125I]IL-1 alpha binding using quantitative autoradiography was significantly decreased in all tissues, including the pituitary gland. Saturation studies in whole testis homogenates demonstrated that the LPS-induced decrease in [125I]IL-1 alpha binding was primarily due to a decrease in the density of IL-1 receptors. These data demonstrate that LPS treatment results in elevated circulating and/or tissue levels of IL-1, which, in turn, down-regulates IL-1 receptors in the brain endocrine-immune axis. PMID- 8462449 TI - Prostaglandin F2 alpha-induced mitogenesis in MC3T3-E1 osteoblasts: role of protein kinase-C-mediated tyrosine phosphorylation. AB - Prostaglandin F2 alpha (PGF2 alpha) stimulates DNA synthesis in osteoblasts through phospholipase-C-dependent increases in intracellular calcium and protein kinase-C (PKC) activity. We present evidence that stimulation of protein tyrosine phosphorylation by PKC is an additional component of the signaling pathways involved in PGF2 alpha-stimulated DNA synthesis in MC3T3-E1 osteoblast-like cells. Mitogenic doses of PGF2 alpha (42 nM) rapidly induced tyrosine phosphorylation of multiple substrates in these osteoblast-like cells. PGF2 alpha stimulated tyrosine phosphorylation of new proteins with apparent mol wt of 87, 80, 50, 47, 36, and 33 kilodaltons and up-regulated phosphorylation of preexisting tyrosine components with mol wt of 123, 112, 68, and 56 kilodaltons. Stimulation of PKC by 1.6 microM phorbol 12-myristate 13-acetate mimicked the pattern of PGF2 alpha-induced protein tyrosine phosphorylation, whereas PKC deficient cells (induced by overnight pretreatment with 16 microM phorbol 12 myristate 13-acetate) were refractory to PGF2 alpha-stimulated protein tyrosine phosphorylation and DNA synthesis. The tyrosine kinase inhibitors tyrphostin and genistein blocked PGF2 alpha-stimulated DNA synthesis and protein tyrosine phosphorylation, and the tyrosine phosphatase inhibitor orthovanadate prolonged PGF2 alpha-stimulated tyrosine phosphorylation; these findings are consistent with activation of a putative tyrosine kinase. Calcium/calmodulin antagonists also inhibited PGF2 alpha-stimulated DNA synthesis, but the calcium-signaling pathway played no role in PGF2 alpha-induced tyrosine phosphorylation. Our findings suggest that cross-talk between receptor-mediated activation of PKC and protein tyrosine phosphorylation is an important distal signaling pathway necessary for PGF2 alpha-induced DNA synthesis in osteoblast-like cells. PMID- 8462450 TI - Pulsatile administration of gonadotropin-releasing hormone does not alter the follicle-stimulating hormone (FSH) isoform distribution pattern of pituitary or circulating FSH in nutritionally growth-restricted ovariectomized lambs. AB - The experimental induction of puberty by GnRH administration to prepubertal lambs increases serum bioactive FSH (B-FSH) as measured in the rat Sertoli cell aromatase induction bioassay. Serum immunoreactive FSH (I-FSH) levels are unchanged. The increase in serum B-FSH is associated with an increase in the proportion of less acidic and more biopotent FSH serum isoforms. However, it is unknown if this effect of GnRH on serum FSH microheterogeneity is direct or mediated by gonadal factors. We have used the nutritionally growth-restricted ovariectomized lamb as a model of the neuroendocrine regulation of FSH isoform microheterogeneity. With this model, the hypothalamic-pituitary component of the neuroendocrine axis may be isolated from gonadal factors. In the present study, using the nutritionally growth-restricted ovariectomized lamb as a model, we investigated the role of GnRH on the regulation of FSH microheterogeneity. Specifically, we tested the hypothesis that GnRH increases the proportion of the less acidic (more biopotent) serum FSH isoforms. As an in vitro correlate, we investigated the effect of GnRH on gonadotropin secretion and FSH isoform distribution in ovine pituitary explant cultures. Seven ovariectomized nutritionally restricted lambs were administered GnRH (i.v., 2 ng/kg) for 36 h (at 2-h intervals for 24 h, then hourly for the final 12 h). Six others served as controls. Blood samples were withdrawn at 12-min intervals during the last 4 h for the measurement of serum immunoactive LH (I-LH) and I-FSH. Pituitary homogenates and serum from four animals from each group were individually chromatofocused, and the FSH isoform distribution patterns were determined. Pulsatile administration of GnRH to nutritionally growth-restricted lambs increased circulating I-LH concentrations from 0.6 +/- 1.0 to 5.9 +/- 3.1 ng/ml (P < 0.01), but did not significantly change circulating I-FSH (4.9 +/- 1.8 vs. 11.5 +/- 4.2 ng/ml) nor B-FSH concentrations (3.9 +/- 1.2 vs. 5.7 +/- 1.5 ng/ml). The pituitary content of I-FSH, B-FSH, and I-LH were unchanged. Neither serum nor pituitary FSH isoform distribution patterns were altered by pulsatile GnRH administration. However, compared to the pituitary FSH isoforms, a higher percentage of circulating FSH isoforms eluted in the salt peak of both groups of lambs. Similar to the in vivo studies, in vitro, GnRH increased the release of I LH, as well as I-FSH, from pituitary explants, but did not significantly change the FSH isoform distribution in either the pituitary explant or media.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8462451 TI - Malic enzyme gene expression in differentiating brown adipocytes: regulation by insulin and triiodothyronine. AB - Primary cultures of brown adipocytes were used to investigate the regulation of malic enzyme (ME) gene expression by insulin and T3. No ME gene expression was detected in undifferentiated preadipocytes. The levels of ME mRNA increased slightly during cell differentiation. Physiological doses of insulin or T3 increased ME gene expression, which reached a maximum after 24 h, on whichever culture day they were added. The effects of insulin and T3 were at the transcriptional level, as measured by run-on assays. Both hormones also increased the stabilization of the transcripts and required ongoing protein synthesis to exert their effects. A comparison of the potencies of insulin and insulin-like growth factor-I and -II (IGF-I and -II) in this system indicated that induction by insulin is mediated via its own receptor. The effects of insulin and T3 were independent of the extracellular glucose concentration, but were additive to that of glucose. Moreover, insulin and T3 act additively to increase ME gene expression, suggesting that they interact either at the transcription level or that of mRNA stabilization. PMID- 8462452 TI - Direct effects of transforming growth factor-beta on chondrocytes are modulated by vitamin D metabolites in a cell maturation-specific manner. AB - Chondrocytes in the endochondral differentiation pathway produce transforming growth factor-beta (TGF-beta) and response to this growth factor both in vitro and in vivo. To clarify the role that cell maturation state plays in the response, we used a well characterized chondrocyte cell culture model which compares cartilage cells at two different stages of maturation. Confluent fourth passage cultures of rat costochondral resting zone and growth zone cartilage cells were incubated with recombinant human (rh) TGF-beta-1 for 24, 48, or 72 h, and the effect on cell number and [3H]thymidine incorporation was observed. To assess whether TGF-beta regulates chondrocyte differentiation to a calcifying cartilage phenotype, cells were incubated for 24 h with TGF-beta, and the specific activities of alkaline phosphatase and phospholipase A2, two enzymes associated with calcification, were assayed in isolated plasma membranes and matrix vesicles. Alkaline phosphatase-specific activity was also measured in the cell layer. Modulation of TGF-beta action by vitamin D metabolites, also known to regulate endochondral differentiation, was examined. The ability of the chondrocytes to produce latent TGF-beta was assayed. The results show that: 1) quiescent chondrocytes at two stages of endochondral maturation respond to rhTGF beta-1 by increasing [3H]thymidine incorporation; 2) growth zone cells exhibit no increase in cell number over a 72-h incubation with TGF-beta, whereas resting zone cells exhibit a dose-dependent increase in cell number at 72 h; 3) nonquiescent cells exhibit an increase in alkaline phosphatase-specific activity at 24 h; 4) the effects on this membrane enzyme are comparable in the plasma membranes and matrix vesicles, but the net effect is greater in the extracellular organelle due to the intrinsically higher levels of activity; 5) although differentiation is promoted in resting zone cells, it is limited in the growth zone cells by inhibition of phospholipase A2 activity; and 6) there is a synergistic enhancement of resting zone chondrocyte differentiation when cells are exposed to rhTGF-beta-1 and 24,25-dihydroxyvitamin D3. PMID- 8462453 TI - Cholecystokinin (CCK)-induced stimulation of luteinizing hormone (LH) secretion in adult male rhesus monkeys: examination of the role of CCK in nutritional regulation of LH secretion. AB - Studies were performed with the overall goal of testing the hypothesis that cholecystokinin (CCK), a peptide hormone released from the gastrointestinal tract in response to meal consumption, provides a metabolic signal which modulates LH secretion in response to changes in the body's nutritional intake. In an initial study to document the effects of CCK on LH secretion in adult male rhesus monkeys, sulfated CCK-8 (7 and 15 micrograms/kg) was administered to six monkeys, and blood samples were collected from indwelling venous catheters. The 15 micrograms/kg dose of CCK elicited a rapid release of LH, with peak LH levels of 31.29 +/- 7.19 ng/ml occurring within 5-15 min. To determine the CCK receptor type mediating the effect of CCK on LH secretion, specific CCK type-A (L-364,718) and type-B (L-365,260) receptor antagonists (1 mg/kg) were administered to five monkeys 15 min before CCK administration. The CCK-A antagonist completely blocked LH secretion in response to CCK, whereas the CCK-B antagonist had no effect. To assess whether endogenous CCK, released in response to food intake, stimulates LH secretion, six monkeys were fasted for 1 day and then provided with a normal meal of monkey chow (i.e. a refeed meal) the following day, with either no antagonist, CCK-A antagonist, or CCK-B antagonist administered 30 min before the meal. As previously demonstrated, meal consumption after a brief period of fasting caused a rapid stimulation of pulsatile LH secretion. The refeed meal led to a comparable stimulation of LH secretion regardless of whether monkeys received no antagonist (3.7 +/- 0.44 LH pulses/9 h), CCK-A antagonist (3.33 +/- 0.56 LH pulses/9 h), or CCK-B antagonist (4.0 +/- 0.78 LH pulses/9 h). These results indicate that CCK can stimulate LH secretion in adult male rhesus monkeys, acting via type-A CCK receptors. However, endogenous CCK released in response to meal intake does not appear to be responsible for the meal-induced stimulation of LH secretion that occurs when monkeys are fed a normal meal after a brief period of fasting. PMID- 8462454 TI - The involvement of inositol phosphoglycan mediators in the modulation of steroidogenesis by insulin and insulin-like growth factor-I. AB - We have investigated the mechanisms by which insulin and insulin-like growth factor-I (IGF-I) regulate the synthesis of progesterone by swine ovary granulosa cells. Analysis of the cell density dependence of the effects of insulin and IGF I showed that the induction of progesterone synthesis by these growth factors is consistent with an autocrine or paracrine model of action, which involves the insulin- and IGF-I-stimulated release of a soluble factor(s) into the culture medium. We have tested the hypothesis that this soluble factor(s) may be structurally related to inositol phosphoglycans, a class of putative second messengers of the action of insulin. Consistent with this hypothesis, we isolated an activator of pyruvate dehydrogenase (PDH) phosphatase from culture medium obtained from cells treated with insulin or IGF-I. Further analysis showed that specific antibodies raised against the inositol phosphoglycan anchor of the variant surface glycoprotein of Trypanosoma brucei blocked the activation of PDH phosphatase by the material isolated from the culture medium, suggesting a close structural relationship between this putative PDH phosphatase activator and inositol phosphaglycans. Pertussis toxin treatment, shown to inhibit the generation of inositol phosphoglycans in other systems, was found to inhibit the effects of insulin on progesterone synthesis in granulosa cells. Finally, the stimulatory effects of insulin and IGF-I on progesterone synthesis by intact granulosa cells were markedly inhibited by the addition of antiinositol phosphoglycan antibodies to the culture medium. Based on these observations, we propose that the release of inositol phosphoglycans into the extracellular medium plays an important role in the signaling mechanisms by which insulin and IGF-I regulate the synthesis of progesterone in swine ovary granulosa cells. PMID- 8462455 TI - Regulation of interleukin 6 gene expression in rat. AB - The effects of ip endotoxin administration on interleukin 6 (IL6) transcripts in brain and in peripheral tissues of rats were studied together with the effects of this treatment on IL6 and corticosterone concentrations in blood serum. Northern blot analyses showed a rapid increase of IL6 transcripts in spleen, pituitary gland, and adrenals that was paralleled by pronounced elevations in serum IL6 and corticosterone levels. Adrenalectomy further enhanced the induction of IL6 messenger RNA (mRNA) in spleen and pituitary gland and augmented the increase in serum IL6 bioactivity after lipopolysaccharide (LPS) injection. Corticosterone pretreatment (10 mg/kg) completely blocked the increase of IL6 in serum and IL6 mRNA in spleen, adrenals, and hypophysis. In several brain areas, low amounts of IL6 mRNA were detected under basal, noninflammatory conditions, but in response to LPS there was no change in the IL6 mRNA in hippocampus, hypothalamus, and cerebellum. Neither adrenalectomy nor peripheral injections of sublethal LPS doses of up to 10 mg/kg were capable of increasing IL6 mRNA in the hippocampus. The data do not support the hypothesis that central IL6 biosynthesis via transcription of the gene contributes to the endotoxin-mediated activation of the hypothalamic-pituitary-adrenal system. The results, however, clearly demonstrate that LPS-induced IL6 gene expression is subject to glucocorticoid suppression in peripheral tissues. PMID- 8462456 TI - The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats. AB - The purpose of this study was to evaluate the dose-effect relationship of recombinant human PTH [hPTH-(1-84)] and synthetic human PTH [sPTH-(1-34)] for the skeleton of estrogen-deplete osteopenic rats. Ex vivo densitometry of regionalized whole femurs and histomorphometry of proximal tibial cancellous bone were the end points. Retired breeder female rats, aged 6-7 months, were used. Ten were killed at baseline, and the rest were ovariectomized (OVX). On day 42, a pre PTH treatment OVX group was killed. The rest were then treated by daily sc injection with hPTH (0, 1.55, 15.5, or 155 micrograms/kg BW.day) or sPTH (0.55, 5.5, or 55 micrograms/kg BW.day) and killed on day 70. The level of cancellous bone mineral was lower in pretreatment OVX rats than at baseline. It was higher in rats treated with 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH than in pretreatment and vehicle-treated OVX rats. Cancellous bone volume was also lower both 42 and 70 days after OVX. Although hPTH did not affect cancellous bone volume, treatment with 5.5-55 micrograms/kg.day sPTH caused higher bone volume than in either pretreatment or vehicle-treated OVX rats. Trabecular number declined after OVX and did not change with PTH treatment. In contrast, trabecular thickness declined after OVX, but was higher after 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH treatment. In OVX rats, the amount of mineralizing surface was greater by day 42 and fell toward control levels by day 70. It was greater in rats treated with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH than in vehicle-treated OVX rats. On a molar basis, sPTH was modestly more potent than hPTH. Osteoclast surface was not affected by PTH treatment. Treating estrogen-deplete osteopenic adult rats for 28 days with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH increases trabecular thickness, but not trabecular number, to cause a rise in bone mass. The extent of mineralizing surface rises without a change in resorption surface. The marked rise in mineralizing surfaces suggests that extended in vivo treatment with PTH activates osteogenic precursor cells near once quiescent surfaces to become osteoblasts. PMID- 8462457 TI - Ligands that activate protein kinase-C differ in their ability to regulate basic fibroblast growth factor and insulin-like growth factor-I messenger ribonucleic acid levels. AB - In this study, rat dermal fibroblasts were used as a model system to examine the ability of ligands that are known to activate protein kinase-C to regulate the levels of the mRNAs encoding basic fibroblast growth factor (bFGF) and insulin like growth factor-I (IGF-I), two growth factors that are thought to be important in processes such as tissue repair and regeneration and wound healing. Treatment of fibroblasts with the phorbol ester phorbol 12-myristate 13-acetate (PMA), thrombin, bradykinin, serotonin, angiotensin-II, or bombesin increased protein kinase-C activity to a similar degree. Treatment of fibroblasts with 1 microM serotonin transiently increased bFGF mRNA levels about 3-fold compared to the level in control cells maintained in serum-free medium with 0.25% BSA and decreased IGF-I mRNA levels by approximately 50% compared to the level in control cells. This is similar to the previously described changes induced by bradykinin in these cells, but different from the more marked and sustained changes induced by thrombin and PMA. In contrast, angiotensin-II and bombesin had no effect on bFGF or IGF-I mRNA levels. The effects of serotonin, bradykinin, and PMA on bFGF and IGF-I mRNA levels were abrogated by preincubation of cells in 250 nM PMA to down-regulate protein kinase-C. In contrast, the effect of thrombin on bFGF mRNA levels was only partially inhibited by down-regulation of protein kinase-C, while its effect on IGF-I mRNA levels was unaffected. The activation of signaling pathways by the different ligands was further investigated to begin to determine the mechanism for the differences in the effects of thrombin vs. serotonin and bradykinin and in the effects of these three ligands vs. angiotensin-II and bombesin. All of the ligands activated phospholipase-D to a similar degree, suggesting that activation of this enzyme was not responsible for the differential effects of the ligands. In contrast, thrombin, serotonin, and bradykinin had marked effects on the hydrolysis of phosphatidylcholine and phosphatidylinositol, whereas bombesin and angiotensin-II had a small effect on phosphatidylcholine hydrolysis and no effect on phosphatidylinositol hydrolysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8462458 TI - Transforming growth factor-beta 1 stimulates chondrogenesis and inhibits osteogenesis in high density culture of periosteum-derived cells. AB - Chick periosteum-derived mesenchymal cells have been reported to exhibit both osteogenic and chondrogenic potentials in high cell density culture conditions. Using this culture system, the effects of transforming growth factor-beta (TGF beta) on proliferation and differentiation of periosteal mesenchymal cells were studied. Supplementation with TGF beta 1 at doses of 0.3-1.0 ng/ml shortened the time course of chondrogenesis and increased the amount of cartilage formed in the lower part of the culture. On the other hand, the amount of bone formed in the upper part of the culture decreased with TGF beta treatment, whereas the time course of osteogenesis remained unaffected. PMID- 8462459 TI - Restoration of estrogen-dependent progesterone receptor expression in a uterine myocyte cell line. AB - Although the in vivo effect of estrogen on myometrial differentiation is well documented, estrogen effects on primary myocytes in vitro have been difficult to demonstrate. To construct a stable uterine myocyte system, capable of direct estrogen responsiveness, we used a transformed hamster myometrial cell line. Since these cells expressed a low level of estrogen receptors (ERs), we have stably transfected them with a vector for the human ER. After transfection, ER concentration increased from less than 300 sites per cell to 17,000 +/- 2,000 sites per cell (mean +/- SEM). To test the functional integrity of the transfected receptors, a chloramphenicol acetyltransferase gene linked to an estrogen response element upstream of thymidine kinase promoter was transiently transfected, and the amount of chloramphenicol acetyltransferase activity, an indicator of estrogen responsiveness, was found to increase 20-fold in response to 17 beta-estradiol (1 nM for 48 h). Furthermore, we tested the ability of estrogen to activate endogenous genes by measuring progesterone receptor (PR) induction. PR concentration in the transfected cells was 3,700 +/- 800 and increased 9-fold to 33,000 +/- 6,000 with 17 beta-estradiol (2 nM). This receptor density increase was confirmed by immunoblotting. PR induction was maximal at 16 h, was concentration dependent, and was not elicited by tamoxifen or ICI 164,384. We conclude that transformed hamster myocytes transfected with an ER gene are capable of estrogen-dependent PR expression in vitro and may serve as a useful system to study estrogen effect on myocytes. PMID- 8462460 TI - Biosynthesis and posttranslational processing of the neurotensin/neuromedin N precursor in the rat medullary thyroid carcinoma 6-23 cell line. Effect of dexamethasone. AB - Neurotensin (NT) and Neuromedin N (NN) are two biologically active peptides present in one copy each in the C-terminal region of a 169-residue precursor. Four basic Lys-Arg doublets occur within the precursor and represent putative processing sites. We investigated the effects of dexamethasone on the biosynthesis and the posttranslational processing of the NT/NN precursor in the rat medullary thyroid carcinoma 6-23 cell line (rMTC 6-23). Western blot analysis and RIA coupled to HPLC and arginine-directed tryptic cleavage of precursor forms were performed with antisera specific for precursor sequences adjacent to the four basic doublets. These studies revealed that rMTC 6-23 cells synthesized the NT/NN precursor in response to dexamethasone and had the capability to process this precursor at the three Lys-Arg doublets that flank and separate NT and NN, thus yielding authentic NT, NN, and several larger products. The most N-terminal Lys-Arg doublet was not processed in this system. Dexamethasone increased in a concentration- and time-dependent manner the levels of all the NT/NN precursor derived products. This increase did not affect the relative proportion of the different products. We also showed by Northern blot analysis that both the 1.1 kilobase and 1.5-kilobase NT/NN precursor messenger RNAs were present in the rMTC 6-23 cell line and that the time course and dose response of dexamethasone induced messenger RNA synthesis were in good agreement with those observed for dexamethasone-induced increase in processing products. The rMTC 6-23 cell line represents a good model to elucidate the steps involved in the posttranslational processing of the NT/NN precursor. PMID- 8462461 TI - Estrogen increases low voltage-activated calcium current density in GH3 anterior pituitary cells. AB - The effects of estrogen (17 beta-estradiol) on calcium current density were examined in the GH3 anterior pituitary cell line. The addition of 1 nM estrogen to the growth medium induces a 4- to 5-fold increase in low voltage-activated (LVA) Ca2+ current density without affecting high voltage-activated Ca2+ current density. The increase is significant after 24 h, reaches a maximum level in 3 days, and reverses with a similar time course when the estrogen is withdrawn. The EC50 for estrogen stimulation of LVA Ca2+ current density is about 30 pM. The LVA current induced by estrogen has similar voltage dependence and time course of activation, inactivation, and deactivation as controls. The effect of estrogen requires protein synthesis, since it is blocked by cycloheximide. It is suggested that the estrogen-induced increase in LVA Ca2+ current density may be due to an increase in the number of functional channels in the membrane. This effect could be due to insertion of new channels or synthesis of a protein that converts preexisting silent channels into functional channels. PMID- 8462462 TI - Regulation of follistatin messenger ribonucleic acid in porcine granulosa cells by epidermal growth factor and the protein kinase-C pathway. AB - Follistatin is a 35-kilodalton monomer isolated from follicular fluid by virtue of its ability to suppress FSH secretion from cultured pituitary cells. Experiments were designed to test the hypothesis that the accumulation of follistatin RNA in the ovary is regulated by epidermal growth factor (EGF) and activation of the protein kinase-C (PKC) pathway. Follistatin mRNA was quantitated by slot blot hybridization of total RNA from primary cultures of porcine granulosa cells treated with the phorbol ester phorbol 12-myristate 13 acetate (PMA), an activator of PKC. PMA (0.1, 1.0, 10, and 100 nM) induced a dose dependent increase in follistatin mRNA accumulation after 2 h, with a maximal increase of 40-fold over that in untreated control cultures at a dose of 10 nM. PMA (10 nM) induced a time-dependent increase in follistatin mRNA levels, with a maximal response at 2 h. Follistatin gene expression was induced by a 2-h incubation with EGF (3 nM), but not by LH (100 ng/ml), GnRH (10 nM) or prostaglandin F2 alpha (80 micrograms/ml). EGF (0.01, 0.1, 1, and 10 nM) induced a dose-dependent induction of follistatin gene expression in granulosa cells after 2-h incubation, with maximal stimulation of 33-fold at a dose of 1 nM. The time course of induction of follistatin mRNA by EGF was very similar to that induced by PMA, with maximal stimulation occurring at 2 h and declining thereafter. Pretreatment of granulosa cells for 24 h with PMA abrogated the EGF induced stimulation of follistatin mRNA accumulation. However, cotreatment of granulosa cells with EGF and PMA for 2 h resulted in additive stimulation of follistatin mRNA. These results demonstrate that 1) follistatin gene expression in cultured porcine granulosa cells is acutely stimulated by PMA and EGF in a time- and dose-dependent manner; 2) follistatin gene expression may be regulated by the PKC pathway; and 3) the stimulatory effect of EGF on follistatin gene expression may require PKC. PMID- 8462463 TI - Dynamic changes in hypothalamic angiotensin II levels and release in association with progesterone-induced luteinizing hormone surge. AB - To test the hypothesis that brain angiotensin II (Ang II) may be involved in the preovulatory release of LH on proestrus, we evaluated the pattern of changes in hypothalamic Ang II levels and release in ovariectomized (ovx) rats treated sequentially with estrogen and progesterone. This is an experimental paradigm that reliably evokes dynamic changes in hypothalamic LHRH levels in association with LH hypersecretion, simulating the LH surge on proestrus. Rats were ovx and after 4 weeks received estradiol benzoate followed by progesterone 2 days later at 1000 h. We observed that in these progesterone-treated rats, serum LH levels were low until 1400 h, but thereafter, the rate of LH secretion increased and remained elevated at 1600 h when the experiment was terminated. In these rats, hypothalamic Ang II levels increased abruptly at 1330 h and returned rapidly to baseline levels before the onset of LH surge. Also, a similar pattern in hypothalamic Ang II levels occurred at 1500 h with the rise and peak serum LH levels in the late afternoon. In the second experiment, Ang II levels in the cerebrospinal fluid (CSF) of rats similarly pretreated with ovarian steroids were evaluated. Again, CSF Ang II levels rose abruptly to a peak at 1330 h and returned to baseline range preceding the expected rise in serum LH. Thereafter, no further change in CSF Ang II levels was detected during the period of LH hypersecretion. In the third experiment, perfusates were collected from a push pull cannula aimed at the paraventricular nucleus in ovx rats similarly treated with ovarian steroids. A peak of Ang II was observed at 1330 h and a later peak at 1430 h. A comparison with LH profiles indicated that these peaks in Ang II levels were evident before and during the LH surge. Thus, in three separate experiments, the results showed that rapid dynamic changes in hypothalamic Ang II levels and release occur in association with the progesterone-induced LH surge in estrogen-primed ovx rats. These findings support the previous observations that Ang II can stimulate LHRH and LH release. Since similar, temporally correlated changes occur in hypothalamic neuropeptide Y and LHRH, the peptides involved in the induction of LH surge, these results are in agreement with the hypothesis that Ang II-expressing neurons may play an important role in the hypothalamic circuitry responsible for stimulation of LH surge in ovarian steroid-treated ovx rats. PMID- 8462464 TI - Relaxin stimulation of porcine granulosa cell deoxyribonucleic acid synthesis in vitro: interactions with insulin and insulin-like growth factor I. AB - Relaxin (RLX) is a product of the theca interna layer of the developing pig follicle. However, its physiological role within the ovary is unknown. The purpose of this study was to determine the effects of RLX alone or in conjunction with insulin and insulin-like growth factor-I (IGF-I) on porcine granulosa cell (GC) DNA synthesis and proliferation in vitro. The results showed RLX (1-1000 ng/ml), insulin (1-1000 ng/ml), and IGF-I (1-30 ng/ml) alone stimulated [3H]thymidine incorporation into DNA by GC from small, medium, and large porcine follicles (P < 0.05). The effect of RLX in combination with insulin or with IGF-I on DNA synthesis by GC from small and medium follicles was greater than the effect of either single factor (P < 0.05). In the large follicle, RLX increased GC DNA synthesis synergistically with insulin and IGF-I. FSH (100 ng/ml) or estradiol (10(-7) M) had no effect on basal or RLX-induced [3H]thymidine incorporation into GC DNA at any stage of follicular development. After 6 days incubation in vitro, RLX dose-dependently increased proliferation of GC from small follicles (P < 0.05). The increased cell number in response to RLX correlates with RLX-induced [3H]thymidine incorporation into DNA by these GC. Hydroxyurea, an inhibitor of DNA synthesis, blocked RLX-induced thymidine incorporation, indicating that the increase in thymidine incorporation in response to RLX was due to DNA synthesis and not repair. This is the first demonstration that RLX acts as a growth factor in the porcine follicle by increasing GC DNA synthesis and proliferation in vitro. RLX enhanced the growth promoting effects of insulin and IGF-I on GC, which suggests an interaction of RLX with these proteins during follicular growth. These studies support the concept that locally produced thecal RLX alone or in combination with other growth effectors may play a key role in GC growth during porcine follicular development. PMID- 8462465 TI - Regulation of parathyroid hormone-related peptide production in vitro by the rat hypercalcemic Leydig cell tumor H-500. AB - The transplantable rat Leydig cell tumor H-500 is known to cause hypercalcemia in vivo by the release of abundant PTH-related peptide (PTHRP) and to closely reproduce the human syndrome of malignancy-associated hypercalcemia. In the rat only a single messenger RNA species of 1.4 kilobases is expressed which encodes a peptide of 141 amino acid as the sole molecular form. We have examined in cultured rat Leydig tumor cells H-500, the capacity of multiple factors to regulate PTHRP messenger RNA expression and secretion. Both fetal bovine serum and epidermal growth factor stimulated PTHRP gene expression and secretion into conditioned culture medium. Dexamethasone and 1,25-dihydroxyvitamin D3 produced inhibition of PTHRP gene expression and secretion. Furthermore, in these testicular cells, after 12 h or more of incubation, testosterone produced a dose dependent (10(-9)-10(-7) M) inhibition of PTHRP production. No significant difference in this inhibitory response was seen between testosterone and its 5 alpha-reduced metabolite dihydrotestosterone whereas 17 beta-estradiol, progesterone, LH, FSH, and PRL were ineffective. An androgen receptor antagonist Win 49596 blocked the androgen-mediated inhibition of PTHRP gene expression and secretion, but not that due to dexamethasone. Epidermal growth factor caused an increase, whereas androgen caused a decrease in PTHRP gene transcription. These studies demonstrated that growth factors, dexamethasone, and 1,25 dihydroxyvitamin D3 are broadly active regulatory agents of PTHRP production which cross species and tissue barriers. Testosterone may be a more selective modulator which can regulate PTHRP in tissues such as Leydig cell neoplasms which express the androgen receptor. PMID- 8462466 TI - Enterohepatic regulation and metabolism of 3,5,3'-triiodothyronine in hypothyroid rats. AB - Several steady state indices of thyroid hormone distribution, metabolism, excretion, and absorption were measured in intact hypothyroid and euthyroid rats, to explore the role of intestines and enterohepatic pathways in the dynamic regulation of whole-body thyroid hormone in these two states. Ten rats were studied, 5 normal control (N) and 5 rendered hypothyroid (3.48 vs. 19.8 ng/ml TSH) by surgical thyroidectomy 3.5 weeks earlier (HYPO). High specific activity 125I-labeled T3 (T3*) was infused at the same constant rate for 7 days from osmotic minipumps implanted sc. Daily urine and feces, and seventh-day cardiac and portal venous blood, bile, and whole intestinal contents were assessed. Bowel and feces were homogenized, extracted, and chromatographed, along with serum, bile, and urine samples. Bile, bowel, and fecal extract samples were also hydrolyzed with aryl-sulfatase and/or beta-glucuronidase and chromatographed to identify conjugates and determine total T3* in all fluid and tissue samples. In the N group, the bowel contained 21.2 +/- 1.22 (SD) times more T3* (mass) than plasma (199 ng vs. 9.39 ng), this ratio falling to 9.03 +/- 1.78 in the HYPO group (30.4 ng vs. 3.37 ng), a shift to relatively more T3* in blood. Urinary T3* was zero in both groups. But fecal excretion was 34 +/- 4.43% of total T3* infused (production) in N and only 20.3 +/- 3.05% in HYPO rats, closely paralleling reduced fecal bulk flow, and thus providing more time for T3* absorption. Endogenous T3 and T4 concentrations measured in portal plasma were 15 31% greater in normals and 69-95% greater in HYPO rats than in corresponding systemic plasma samples, a direct indication of absorption of endogenous T3 and T4 in both groups, with greater absorption in the HYPO group. About 66% total T3* was metabolically degraded in N rats, rising to approximately 80% in HYPO rats. Plasma clearance rates of T3 fell more than 50% in HYPO rats, and total T3 production fell to about 20% of normal. It appears that HYPO rats compensate for low T3 by fecally excreting a much smaller fraction of total T3 production, absorbing more T3 and T4, and leaving a larger fraction for T3 action and degradative metabolism. PMID- 8462467 TI - The stimulatory effect of insulin on diacylglycerol generation in adipocyte membranes from ob/ob mice is impaired by growth hormone. AB - Physiologically, the action of insulin on carbohydrate and lipid metabolism is opposed by several hormones, including glucocorticoids, glucagon, catecholamines, and pituitary GH. Perhaps least is known about the mechanism(s) involved in the antiinsulin action of GH. Since the generation of diacylglycerol (DAG) appears to be an early event in the insulin-signaling cascade, it was of interest to determine whether GH would interfere with this effect of insulin. Experiments were conducted to determine whether insulin would stimulate the generation of DAG in adipocytes of the obese (ob/ob) mouse, and whether this response could be blocked by the diabetogenic GH derivative S-carboxymethylated human GH (RCM-hGH). Isolated adipocytes of the ob/ob mouse were used for these studies, because unlike normal rodents, the ob/ob mouse responds predictably to the antiinsulin action of GH. Insulin produced a rapid biphasic increase in the amount of DAG in a crude membrane fraction of the adipocytes. The first peak in DAG mass occurred within 5 min of exposure of the cells to insulin, and the second peak occurred after 30 min. The first peak in DAG mass did not occur in adipocytes that had been incubated with pertussis toxin before exposure to insulin. Also, adipocytes isolated from ob/ob mice that had been treated with RCM-hGH failed to respond to insulin with an increase in DAG mass. RCM-hGH blocked both the first and second insulin-induced peaks in DAG mass within 6 h of its administration. This is the time at which ob/ob mouse adipocytes exhibit increased insulin resistance in response to RCM-hGH. Neither exposure to insulin nor treatment with RCM-hGH had any appreciable effect on the fatty acid composition of the DAG present in the adipocyte membranes. These findings are compatible with the idea that GH produces some defect in the insulin-signaling cascade that is proximal to the events that result in the generation of DAG in the adipocyte. PMID- 8462468 TI - Seasonal changes in melatonin binding sites in the pars tuberalis of male European hamsters and the effect of testosterone manipulation. AB - Seasonal changes in specific 2-[125I]iodo-melatonin binding were assessed in the pars tuberalis of male European hamsters (Cricetus cricetus) kept under natural environmental conditions. Saturation studies were performed on pars tuberalis membrane preparations every 5-7 weeks for 13 months. The maximum number of melatonin binding sites occurred in spring and summer (Bmax, 4.0 +/- 0.3 fmol/mg protein, n = 9) with significantly reduced binding in winter (Bmax, 1.2 +/- 0.2 fmol/mg protein, n = 2). As an assay control, simultaneous saturation studies were performed on rat pars tuberalis membranes. No summer-winter difference in binding site density was observed in the rat studies. In both hamsters and rats no seasonal changes in binding affinity were found. Although an apparent correlation between Bmax, values and paired testes weight of the hamsters was noted, in early spring the increase in the number of melatonin binding sites preceded the elevation in testicular weight. Castration during the period of sexual activity or sexual inactivity also failed to reduce the elevated number of binding sites observed in the spring and summer. In addition, testosterone implanted sc 5 weeks before had no effect on the low 2-[125I]iodo-melatonin binding site density found in winter (November). These results suggest that the observed seasonal variation in the number of melatonin binding sites is independent of seasonal changes in circulating testosterone concentrations. PMID- 8462469 TI - A supersensitive immunofluorometric assay for rat luteinizing hormone. AB - We have developed an immunofluorometric assay (IFMA) for rat (r) LH, which is based on two monoclonal antibodies, one to bovine and the other to human LH. Signal detection occurs by time-resolved fluorescence evoked by a europium label (Delfia, Wallac). The method is fast in comparison to the standard RIA with the NIDDK reagents (4 h vs. 3 days). The sensitivity of the IFMA assay (0.75 pg/tube; NIDDK rLH RP-2) is over 30-fold higher than that of the NIDDK RIA (usual detection limit, 20-30 pg/tube). Using 25-microliters serum samples, the sensitivity of IFMA is 0.03 micrograms/liter; with 100-microliters samples, it is 0.0075 micrograms/liter. The cross-reactivity of the IFMA assay is 0.3% with rFSH, 3% with rTSH, and less than 0.05% with rGH, rPRL, and the rat alpha subunit. A linear correlation between IFMA and RIA values is seen at serum levels above 0.4 micrograms/liter. Below this level, only IFMA is able to detect concentration differences between samples. In practice, this means that only IFMA is able to provide meaningful measurements of suppressed levels of serum LH. The correlation coefficient between IFMA and the mouse interstitial cell in vitro bioassay for LH in randomly selected rat pituitary homogenates was 0.93 (n = 47). The serum concentration of LH determined by IFMA is 0.57 +/- 0.10 micrograms/liter in intact adult male rats (mean +/- SEM; n = 12) and 0.41 +/- 0.10 micrograms/liter (n = 10) in randomly cycling females. The level in hypophysectomized rat serum is 0.035 +/- 0.0033 micrograms/liter (n = 8), if the limit of sensitivity (0.03 microgram/liter) is assigned to unmeasurable levels. One-week treatment of male rats with 2-cm Silastic implants containing testosterone suppressed serum LH, measured by IFMA, from 0.56 +/- 0.057 to 0.086 +/- 0.057 micrograms/liter (P < 0.01). The suppression of LH measured in the same samples by RIA was lower, from 0.73 +/- 0.057 to 0.44 +/- 0.048 micrograms/liter (P < 0.01). A 5-day starvation of intact male rats suppressed serum LH from 0.57 +/- 0.10 to 0.30 +/- 0.05 microgram/liter by IFMA (P < 0.01), whereas the decrease determined by RIA was not significant (0.80 +/- 0.07 vs. 0.66 +/- 0.13 micrograms/liter).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8462470 TI - Cholesterol cell content affects prolactin but not growth hormone release in GH4C1 cells. AB - It is generally accepted that cholesterol affects dynamic membrane properties and the function of membrane bound proteins involved in secretion processes. In the present study we employed GH4C1 cells treated with human lipoprotein-deficient serum (h-LPDS), exogenous cholesterol and high density lipoprotein (HDL3) to investigate the role of cholesterol cell content on PRL and GH basal release. Incubation of GH4C1 cells with h-LPDS decreased free cholesterol content and cholesterol added to the media increased it. HDL3 did not act as a cholesterol acceptor in either cholesterol-depleted or cholesterol-loaded cells; however, in depleted cells HDL3 was a net donor, significantly increasing cell cholesterol. Control or cholesterol loaded cells incubated in media with h-LPDS increased their secretion of PRL in parallel with the loss of cell cholesterol. Conversely, the addition of either cholesterol or HDL3 to cholesterol depleted cells inhibited PRL release. However, GH secretion was not modified by changes in free cholesterol in any of these situations. In the experiments in which HDL3 was present, a highly positive correlation was found between cholesterol cell content at the end of the experiment and PRL secretion, no effect could be related to the amount of added HDL3, suggesting that the HDL3 had no specific effect on the secretion of PRL or GH. Our results indicate that cholesterol cell content is an important factor in the release of PRL but not of GH, and emphasize the differences in the basal regulation of the secretion of both hormones. PMID- 8462471 TI - Increased angiotensin II type-1 receptor gene expression in neuronal cultures from spontaneously hypertensive rats. AB - In this study we compared the expression of angiotensin II type 1 (AT1) receptor messenger RNA (mRNA) and AT1 receptors in neurons cultured from Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rat brains. Neuronal cultures from the hypothalamus and brain-stem of 1-day-old SH rats exhibited approximately 4-fold higher steady-state levels of AT1 receptor mRNA than the corresponding WKY cultures. This was attributable to greater levels of both AT1A and AT1B receptor mRNA subtypes in SH rat neuronal cultures compared with WKY rat neurons. SH rat neuronal cultures also exhibited increased numbers (approximately 2.3-fold) of binding sites for [3H]DuP753, an AT1 receptor selective ligand, and enhanced (approximately 3.4-fold) stimulation of inositol phospholipid hydrolysis by angiotensin II compared with WKY neurons. By contrast, cultured astroglia from SH and WKY rat brain exhibited no significant differences in either the levels of AT1 receptor mRNA or the specific binding of [3H]DuP753. These data suggest that in SH rat neurons, AT1 receptor transcription and translation is increased, compared with neurons from WKY rats. PMID- 8462472 TI - Cholecystokinin stimulates gonadotropin-releasing hormone release in the monkey (Macaca mulatta). AB - There is evidence to suggest that the arginine vasopressin release observed in association with emesis after i.v. injection of cholecystokinin (CCK) and N methyl-D-aspartate (NMDA) is mediated by stimulation of emetic centers in the brainstem. That the GnRH-releasing action of NMDA is also sometimes accompanied by emesis led to the suggestion that stimulation of this parvocellular system by the glutamate agonist may also be mediated in part via activation of brainstem pathways. If this is the case, then other nauseogenic agents, such as CCK, should similarly elicit GnRH release. The foregoing prediction was tested in the castrated juvenile male monkey, an experimental model characterized by the absence of spontaneous GnRH release. GnRH discharges were monitored indirectly by measuring changes in circulating LH concentrations after the responsivity of the gonadotroph had been heightened by a chronic intermittent i.v. infusion of the decapeptide. An i.v. bolus of CCK at 10 and 30 micrograms/kg BW led to a distinct discharge of GnRH accompanied by emesis or other behaviors suggestive of nausea. Lower doses of CCK (1 and 3 micrograms/kg BW) failed to significantly perturb GnRH release or cause emesis, although NMDA (5 mg/kg BW; racemic form) injected i.v. 3 h after the CCK challenge led to a robust rise in GnRH. In a parallel study, three repetitive i.v. CCK injections at 2h intervals maintained intermittent GnRH release. Pretreatment with a long-acting GnRH receptor antagonist ([AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10]GnRH -HOAc) abolished the LH response to CCK, confirming that the action of this peptide was mediated by GnRH release. Although a direct hypothalamic site of action for these agents remains the most likely possibility, since both NMDA and CCK receptors are present in the infundibular region, the present data are consistent with the notion that CCK and, by inference, NMDA may activate GnRH release in part via the stimulation of brainstem emetic centers. Plasma GH, PRL, and cortisol concentrations were also monitored during the course of some of these experiments, and the release of these hormones was observed after the administration of either the 10 or 30 micrograms/kg BW dose of CCK. PMID- 8462473 TI - Mitogenic signaling by prostaglandins in chemically transformed mouse fibroblasts: comparison with phorbol esters and insulin. AB - In the quiescent mouse BP-A31 fibroblasts, prostaglandin F2 alpha (PGF2 alpha) induces the expression of cell cycle-related genes c-fos, c-jun, and c-myc, and after a delay of approximately 12 h the entry into the phase of DNA replication. A weaker mitogenic effect was produced by certain other PGs (F1 alpha > D2), whereas the effects of PGs E and I were marginal or absent. The mitogenic effects of PGF2 alpha as well as of 12-O-tetradecanoyl phorbol 13-acetate (TPA; activator of protein kinase C) but not those of insulin (acting via the insulin-like growth factor 1 receptor) were abolished by a low concentration (7.5 nM) of staurosporine (inhibitor of protein kinase C). Moreover, long-time (24 h) preincubation with phorbol dibutyrate reduced the mitogenic effects of a subsequent exposure either TPA or PGF2 alpha. These observations favor the involvement of protein kinase C in the PGF2 alpha-dependent intracellular signal transduction. However, simultaneous stimulation of the quiescent cells with saturating concentrations of PGF2 alpha and TPA had a greater mitogenic effect than either drug alone, both in cells with and without down-regulation of protein kinase C, indicating that the protein kinase C-dependent signaling does not entirely account for the mitogenic activity of PGF2 alpha. PMID- 8462474 TI - Transfer kinetics of 3,5,3'-triiodothyronine and thyroxine from rat blood to large and small intestines, liver, and kidneys in vivo. AB - Enterohepatic circulation of thyroid hormone in the rat involves transfer of hormone to intestines in bile from the liver and absorption of some intestinal hormone, via portal blood to liver. Transfer of hormone to intestines from mesenteric arterial blood has generally been considered minimal, although this alternate pathway has received little attention. We have measured uptake kinetics of iv trace doses of radioactivity labeled T3 (T3*) and T4* from blood to intestines, longitudinally in 14 segments of total intestines in situ, with bowel contents included and bile duct ligated, and also to liver and kidneys, for comparison. Both T3* and T4* entered the entire length of intestines from blood, and into contents as well as tissue. Tissue uptake of T3* and T4* were fairly uniform longitudinally, but uptake into contents and thus into total intestines (tissue + contents) decreased linearly from pylorus to anus. Unidirectional uptake rate constants (hours-1) or clearance rates (milliliters per h) of T3* were 13 times greater than corresponding T4* fractional uptake rates to intestines. In contrast, T4 mass fluxes (congruent to 38 ng/h.100 g body wt) exceed T3 fluxes (congruent to 6.3 ng/h.100 g body wt) about 6-fold, because plasma contains far more T4 than T3. Comparing these results with published biliary and fecal T3 and T4 flux data, it appears that mesenteric arterial mass influxes to intestines are 3-5 times greater than both biliary secretion and fecal excretion of T3 and T4. Intestinal kinetics, in the absence of biliary influx, are characterized by a moderately rapid uptake followed by a very slow washout phase, which fit into neither the fast nor slow compartment paradigms of a 3-compartment mammillary model, in contrast to liver and kidney kinetics, which fit well into a single fast compartment. Intestinal dynamics are consistent with an organ in which storage and exchange of thyroid hormone dominate over metabolic and excretory processes. PMID- 8462475 TI - Transforming growth factor-beta 1 modulates calcium metabolism in Sertoli cells. AB - The mechanism of signal transduction by transforming growth factor-beta 1 (TGF beta 1) is largely unknown. In this study, TGF-beta 1 was able to stimulate 45Ca2+ uptake in cultured rat Sertoli cells. In contrast to the rapid stimulation of 45Ca2+ uptake previously observed in response to FSH (< 1 min), the response to TGF-beta 1 required several hours and was abolished by actinomycin-D. Although TGF-beta 1 had no effect on basal calcium uptake before 1 h, it completely inhibited the FSH-stimulated calcium uptake in short term incubations (2 and 20 min). These effects of TGF-beta 1 on calcium metabolism may be directly related to the ability of this cytokine to regulate cell growth and differentiation in many cell systems. PMID- 8462476 TI - Effects of estrous cycle stage and pregnancy on follistatin gene expression and immunoreactivity in rat reproductive tissues: progesterone is implicated in regulating uterine gene expression. AB - Follistatin, a monomeric protein originally isolated from ovarian follicular fluid, is now believed to be a major local regulator of the multifaceted actions of activin by virtue of its activin-binding properties. In view of the ability of follistatin to stimulate progesterone production from granulosa cells and its presence in newly formed corpora lutea, the following study was conducted to determine the effects of cycle stage and pregnancy on follistatin gene expression and immunoreactivity in the rat ovary and uterus with the intent of gaining additional insights into the regulation of follistatin in these tissues. Decidua and placentas were also examined on days 15, 18, and 21 of pregnancy. Follistatin messenger RNA (mRNA) levels were quantified using a sensitive solution hybridization-RNase protection assay and values normalized to the amount of cyclophilin mRNA present in each sample. Levels of follistatin-like immunoreactivity (FLI) in serum and tissues were estimated using a homologous porcine follistatin RIA. Follistatin message levels in the ovary increased between proestrus and estrus with a return to proestrous values on both days of diestrus. In the nonpregnant uterus, mRNA levels on proestrus were similar to levels measured in uteri taken from hypophysectomized or ovariectomized rats. Interestingly, follistatin gene expression increased almost 3-fold between proestrus and estrus. An additional experiment demonstrated that this increase could be abated by treatment of proestrous rats with pentobarbital which blocks preovulatory rises in serum progesterone levels and could be restored by administration of progesterone to pentobarbital-treated proestrous rats. In pregnant rats, ovarian follistatin message levels on days 3 and 6 of pregnancy were identical to levels observed on day 2 of diestrus. However, an abrupt 4-fold increase in ovarian mRNA levels occurred between days 6 and 9 with a further 58% increase occurring by day 12. This marked increase in message levels was unaccompanied by changes in ovarian FLI levels. A precipitous decrease in transcript levels accompanied by a decline in FLI levels then followed with ovarian gene expression on days 15 through 21 being slightly higher than expression during the initial stages of gestation. Expression of the gene in the decidua and placenta did not vary between days 15 and 21 of pregnancy. Levels of FLI in serum also were invariant during the cycle and pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8462477 TI - Differential regulation of transcription initiation from insulin-like growth factor-I (IGF-I) leader exons and of tissue IGF-I expression in response to changed growth hormone and nutritional status in sheep. AB - In the mammalian insulin-like growth factor-I (IGF-I) gene, exons 1 and 2 are differentially spliced to exon 3 producing alternate class 1 and class 2 transcripts. The aim of this study was to investigate the tissue expression of these leader exons in lambs growing at different rates as a result of chronic manipulation of nutritional and GH status. Riboprobes were developed so that leader exon-specific and total IGF-I gene expression could be determined using a single RNase protection assay. Lambs were fed a diet containing high or low protein content either ad libitum or at a restricted intake; within these dietary groups they were treated with either saline or GH for 10 weeks. Total hepatic IGF I messenger RNA (mRNA) transcripts were significantly increased by GH (P = 0.004), protein (P = 0.002), and energy (P < 0.001) status as were circulating IGF-I concentrations (GH, P < 0.001; protein, P = 0.026; energy, P < 0.001). Exons 1 and 2 were expressed in liver but to a variable extent. Increased dietary energy and protein induced increased expression from both class 1 and 2 transcripts, but the percent increases was at least 5-fold greater for class 2 than for class 1 mRNA. GH treatment only stimulated significant increases in expression from class 2 transcripts. In the low protein, energy-restricted, saline-treated lambs exon 1 transcripts accounted for approximately 70% of total class 1 and 2 transcripts, and this proportion declined significantly as class 1 and 2 transcripts, and this proportion declined significantly as GH and nutritional status increased to only 30% in the high protein, ad libitum-fed, GH treated animals; class 2 transcripts therefore displayed the opposite pattern of expression. These data indicate that exon 2 may be far more sensitive than exon 1 in intact animals which have been stimulated within normal physiological limits. Muscle IGF-I gene expression was at least 20-fold less than that for the liver and consisted mainly of class 1 transcripts. Muscle total IGF-I mRNA was insensitive to changed nutritional status or to GH treatment, even though significant increases in muscle growth occurred in response to ad libitum intake and GH, indicating that hepatically derived endocrine IGF-I could have a role in the regulation of muscle growth. PMID- 8462478 TI - Enhancement of thyrotropin-stimulated iodide organification in porcine thyroid cells after protein kinase-C inhibition. AB - We and others have previously shown that 12-O-tetracanoylphorbol-13-acetate (TPA), a protein kinase-C (PKC) activator, inhibits TSH-stimulated iodide organification in porcine thyroid cells. However, TPA action may be independent of PKC. To further explore the role of PKC in the regulation of differentiated thyroid function, we studied the effects of the PKC inhibitors 1-O-hexadecyl-2-O methylglycerol (AMG-C16), 1-(5-isoquinolinesulfonyl)2-methylpiperazine (H7), and staurosporine on TSH-stimulated iodide organification in porcine thyroid cells in the presence and absence of TPA. AMG-C16 increased basal iodide organification in concentrations ranging from 15-240 microM (P < 0.01, by analysis of variance). Such stimulation by AMG-C16 (30-120 microM) persisted in the presence of submaximal (10 microU) and maximal (1 mU) concentrations of TSH. However, in the presence of TPA (> 10 nM), the effects of AMG-C16 were abolished. H7 (50 microM) and staurosporine (100 nM) also enhanced TSH-stimulated iodide organification. In the presence of staurosporine and TPA, no inhibition of TSH-stimulated iodide organification was observed. However, H7 could not reverse the effects of TPA. In summary, these studies indicate that in porcine thyroid cells, three distinct PKC inhibitors all enhanced TSH-stimulated iodide organification and that staurosporine reversed the effects of TPA on TSH-stimulated iodide organification. These findings are consistent with the concept that PKC acts as an endogenous negative modulator of iodide organification in vitro. PMID- 8462479 TI - Neuropeptide-Y stimulates growth hormone and gonadotropin-II secretion in the goldfish pituitary: involvement of both presynaptic and pituitary cell actions. AB - We have previously reported that neuropeptide-Y (NPY) stimulates GH and gonadotropin-II (GtH-II) release from perifused pituitary fragments in the goldfish. Since the teleost pituitary is directly innervated by neurosecretory terminals from the brain, we further investigated the possible sites of action of NPY. Both synthetic human NPY and NPY-(18-36), an agonist selective for the NPY Y2-receptor, stimulated GH and GtH-II release from the pituitary fragments; the magnitude of the response to NPY (18-36) was smaller than that to the whole molecule of NPY. NPY also stimulated the release of GH and GtH-II from perifused dispersed pituitary cells. In contrast, NPY-(18-36) had no effect on either GH or GtH-II release from dispersed pituitary cells. These data suggest that Y2 action is not direct at the level of pituitary cells, but may be indirect through actions on nerve terminals in the pituitary. The hypothesis that the action of NPY on GH and GtH-II release is mediated in part by GnRH was then tested. Both NPY and NPY-(18-36) stimulated the GnRH release from preoptic-anterior hypothalamic slices and pituitary fragments with similar potency. Furthermore, a GnRH antagonist significantly reduced the effects of NPY on both GH and GtH-II release in perifused pituitary fragments. Similar to previous findings, NPY, when given at 55-min intervals, desensitized the hormone responses in pituitary fragments. Similarly, the same treatment with NPY in perifused dispersed pituitary cells induced desensitization of GH and GtH-II responses. Together, these results suggest that 1) more than one type of NPY receptors are present in the goldfish pituitary; and 2) NPY has at least two sites of action in the pituitary. One site of action is the pituitary cells, where NPY directly stimulates GH and GtH-II secretion; the second is the nerve terminals, where NPY presynaptically stimulates GnRH release via Y2-like receptors, and GnRH, in turn, stimulates GH and GtH-II release. PMID- 8462480 TI - Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment. AB - We previously reported that RU486 can reverse progesterone (P)-induced suppression of the estrogen receptor (ER) in the uterus of pregnant rhesus monkeys, but we did not determine whether estrogen (E) could act through its receptor in the presence of P and RU486. To pursue this question, we treated spayed rhesus monkeys with various hormonal regimens and evaluated the effects of E in the oviduct and endometrium, with and without RU486 treatment, on ER and progestin receptor (PR) levels, morphology, apoptosis, and degree of proliferation. The latter was assessed immunocytochemically with a monoclonal antibody (Ki-67) against a nuclear antigen present only in proliferating cells. Animals were treated for 2 weeks with 17 beta-estradiol (E2) and then for 2 weeks with E2 plus P to produce a regressed oviduct and a secretory endometrium. The animals were then treated for 2 more weeks with four different treatments, as follows: I) E2, P, and vehicle; II) E2 and vehicle; III) E2, P, and RU486; and IV) E2 and RU486 (n = 4 each). In group I, menstruation did not occur, and the endometrium exhibited stromal cell enlargement, extensive development of the spiral arteries, few Ki-67-positive cells, and low levels of ER and PR. Oviducts in group I remained regressed, Ki-67-positive epithelial cells were few, and levels of ER and PR were low. In contrast, in groups II, III, and IV, the oviducts had responded to E2 and were fully ciliated and secretory, with elevated levels of ER and nuclear PR. All animals in these three groups menstruated and then regenerated their endometrium. The regenerated endometria expressed elevations in ER, nuclear PR, and epithelial Ki-67 index. However, the endometria of RU486-treated monkeys in groups III and IV had significantly more epithelial cell death by apoptosis, increased stromal cell compaction, and fewer Ki-67 positive stromal cells than in the E2 controls (group II). In group IV, RU486 caused a significant decrease in endometrial weight. Thus, RU486 blocked P action and allowed E2 to act in a normal fashion in the oviduct and endometrium on several end points, but it also had antiproliferative effects that opposed E2 action, especially in the endometrium. PMID- 8462481 TI - Expression of the genes for the epidermal growth factor receptor and its ligands in porcine corpora lutea. AB - Using reverse transcription-polymerase chain reaction (RT-PCR), transcripts for EGF receptor and for EGF, transforming growth factor-alpha (TGF alpha), amphiregulin (AR) and heparin binding-EGF (HB-EGF) were detected in porcine corpora lutea at day 4, 10 and 20 of the estrous cycle. No cycle-dependent changes were apparent in the expression of the receptor, AR or TGF alpha. In contrast, HB-EGF mRNA levels appeared highest on day 4 during luteal growth and development, whereas EGF mRNA levels appeared highest on day 20 when the corpora lutea undergo luteolysis. These results suggest that luteal function may be subject to regulation by members of the EGF family acting in an autocrine, paracrine or intracrine manner. PMID- 8462482 TI - Porcine oocytes release cumulus expansion-enabling activity even though porcine cumulus expansion in vitro is independent of the oocyte. AB - In the mouse, the oocyte secretes a factor that enables cumulus cells to undergo expansion in response to epidermal growth factor (EGF) or FSH while expansion of the porcine cumulus oophorus has been shown to be independent of the oocyte. This study was undertaken to confirm independence of the porcine cumulus oophorus of the oocyte for its expansion and to determine if the porcine oocyte secretes the putative cumulus expansion-enabling factor that is required for FSH-stimulated mouse cumulus expansion. Porcine oocyte-cumulus cell complexes (P-OCC), oocytectomized oocyte-cumulus cell complexes (P-OOX) and intact clumps of cumulus cells (P-CCC) were cultured at 39 C in TCM-199 medium containing EGF (1 ng/ml) or FSH (1.5 micrograms/ml). After 24h culture periods, cumulus expansion was scored on an arbitrary scale of 0 to +4. EGF stimulated similar cumulus expansion (expansion score +3 compared to 0 for controls) in all the three groups. FSH stimulated cumulus expansion in significantly higher number of complexes in all groups compared to EGF. However, there was no difference in cumulus expansion among the three groups with EGF or FSH. To determine the production of the factor by the porcine oocyte, isolated clumps of cumulus cells of the mouse (M-CCC) were cocultured with porcine denuded oocytes (P-DO) in TCM-199 with or without 1.5 micrograms/ml FSH at 37 C for 24h. No expansion was observed when M-CCC were cultured alone in the presence of FSH or cocultured with P-DO in the absence of FSH. However, coculture of M-CCC with P-DO in the presence of FSH resulted in expansion of M-CCC similar to that observed in intact mouse oocyte-cumulus cell complexes (M-OCC) in response to FSH. These studies indicate that even though porcine cumulus expansion in vitro is not dependent on the oocyte, the porcine oocyte is capable of secreting cumulus expansion-enabling factor(s). PMID- 8462483 TI - Evidence for generation of the growth hormone-binding protein through proteolysis of the growth hormone membrane receptor. AB - The growth hormone-binding protein (GHBP) which circulates in plasma is a soluble short form of the membrane growth hormone receptor (GHR). In rats and mice, GHR and GHBP originate from two alternatively spliced mRNAs (4.5 and 1.2 kb). In human and rabbit tissues, a single predominant mRNA of 4.5 kb was detected and it was hypothesized that GHBP could be produced by proteolytic cleavage of the GHR. Using gel filtration and HPLC, we have detected a high level of GH binding activity in media of cells transfected with rabbit GHR cDNA. The [125I]hGH-GHBP complex eluted at the same time as the plasma complex and both the binding affinity and specificity of the BP were comparable to that of rabbit plasma. Immunoprecipitation experiments and Western blots confirmed that GHBP in the media of transfected cells was a 55 kDa protein related to the extracellular domain of the GHR. In contrast, no BP was detected in the media of cells transfected with the cDNA encoding the rat GHR. These results strongly suggest that, in rabbit and probably in man, the GHBP could, at least in part, be produced by proteolytic cleavage of the GHR. PMID- 8462484 TI - Selenium deficiency aggravates the necrotizing effects of a high iodide dose in iodine deficient rats. AB - The effect of selenium deficiency associated with various iodide intake was investigated in rats in order to better understand its possible role in the etiopathogeny of myxedematous cretinism. Groups of rat pups were fed from birth a low selenium diet (Se-) and submitted to goitrogenic treatment (1% perchlorate in water) for one month. Some animals were refed iodide after perchlorate withdrawal. The gland morphology was analyzed in correlation with the glutathione peroxidase (GPX) activity and the thyroid hormone plasma levels. In all Se- rats, the GPX activity was strongly reduced as compared to selenium sufficient (Se+) animals (P < 0.01). Goitrous rats were hypothyroid whatever the selenium intake. After iodide refeeding, plasma T4 and T3 levels were increased by 160% in Se- rats and by respectively 330% and 580% in Se+ rats. The thyroid morphology was different according to the selenium intake: necrotic cells were about three times more numerous in Se- than in Se+ rats (P < 0.01) and the inflammatory reaction was increased. These experimental data demonstrate the detrimental role of selenium deficiency in one experimental case of thyroid disease. Such reduction of cell defences could contribute to the thyroid failure of African myxedematous cretins. PMID- 8462485 TI - Detection of C-type natriuretic peptide (CNP) transcript in the rat heart and immune organs. AB - Previous studies suggested the expression of mRNA, coding for CNP, exclusively in the central nervous system. In the present study, using the polymerase chain reaction (PCR) technique instead of the less sensitive Northern blot hybridization, CNP-specific sequences have also been detected in rat atria and ventricles of the heart as well as in organs of the immune system (thymus, spleen and lymph nodes). Parallel PCR-assays documented ANP-mRNA in these tissues. To verify specificity of the PCR-products, Southern blots have been hybridized with a third internal oligonucleotide and amplification products have been sequenced. The relative level of CNP-mRNA in these tissues was estimated to be in the range of 1-9% of total brain CNP transcripts. The results suggest that the peptide may have a peripheral as well as a central site of action. In light of its pronounced effect on cell proliferation, particular interest should focus on a possible role of CNP in the immune system. PMID- 8462487 TI - Status epilepticus. Proceedings of the American Epilepsy Society Course. Philadelphia, Pennsylvania, December 1991. PMID- 8462488 TI - Convulsive status epilepticus in children. AB - Status epilepticus (SE) occurs most commonly in infancy and childhood. Children with prior neurological abnormalities are most susceptible. More than 90% of cases are convulsive and the majority are generalized. SE may occur in the setting of an acute illness, in patients with established epilepsy or as a first unprovoked seizure. The etiology can be classified as idiopathic, remote symptomatic, febrile, acute symptomatic, or associated with a progressive encephalopathy. The morbidity and mortality of status have dramatically declined in recent years. Overall mortality in recent pediatric series was 3-10%, with almost all fatalities associated with acute central nervous system insults or progressive neurologic disorders. Neurological sequelae in children with idiopathic or febrile status are rare. Neurologically normal children with SE as their first unprovoked seizure have the same risk of experiencing subsequent seizures of any type as children who present with a brief first seizure. The risk of recurrent episodes of convulsive SE approaches 50% in neurologically abnormal children but is very low in neurologically normal children. The favorable outcome of SE in children may be related to advances in therapy and to the resistance of the immature brain to damage from seizures. PMID- 8462486 TI - Regulation of c-fos proto-oncogene expression by growth hormone: protein synthesis is not required for down-regulation. AB - Growth hormone (GH) has been previously shown in Ob1771 adipose cells to transiently stimulate the expression of the c-fos gene by a protein kinase C (PKC)-dependent pathway. This regulation takes place at a transcriptional level. In the presence of cycloheximide (CHX), stimulation by PKC activators or by serum leads to a "superinduction" of the c-fos gene. In contrast, upon GH stimulation in the presence of CHX, no superinduction takes place and neither prolonged transcription nor mRNA stabilization are observed. PMID- 8462489 TI - Generalized convulsive status epilepticus in the adult. AB - Status epilepticus (SE) is defined as recurrent epileptic seizures without full recovery of consciousness before the next seizure begins, or more-or-less continuous clinical and/or electrical seizure activity lasting for more than 30 min whether or not consciousness is impaired. Three presentations of SE are now recognized: recurrent generalized tonic and/or clonic seizures without full recovery of consciousness between attacks, nonconvulsive status where the patient appears to be in a prolonged "epileptic twilight state," and continuous/repetitive focal seizure activity without alteration of consciousness. Generalized convulsive status epilepticus (GCSE) encompasses a broad spectrum of clinical presentations from repeated overt generalized tonic-clonic seizures to subtle convulsive movements in a profoundly comatose patient. Thus, GCSE is a dynamic state that is characterized by paroxysmal or continuous tonic and/or clonic motor activity, which may be symmetrical or asymmetrical and overt or subtle but which is associated with a marked impairment of consciousness and with bilateral (although frequently asymmetrical) ictal discharges on the EEG. Just as there is a progression from overt to increasingly subtle clinical manifestations of GCSE, there is also a predictable sequence of progressive EEG changes during untreated GCSE. A sequence of five patterns of ictal discharges has been observed: discrete electrographic seizures, waxing and waning, continuous, continuous with flat periods, and periodic epileptiform discharges on a relatively flat background. A patient actively having seizures or comatose who exhibits any of these patterns on EEG should be considered to be in GCSE and should be treated aggressively to stop all clinical and electrical seizure activity to prevent further neurological morbidity and mortality. PMID- 8462490 TI - Nonconvulsive status epilepticus in adults and children. AB - Nonconvulsive status epilepticus (SE) accounts for approximately one-quarter of all cases of SE. The actual proportion may be higher because patients with nonconvulsive SE may go unidentified. This disorder may be divided into generalized (absence) or partial (complex partial) forms. Nonconvulsive SE may occur de novo or in patients with epilepsy. Absence SE is considered more frequent and is characterized by a continuous neurocognitive alteration. Complex partial SE may be associated with recurrent seizure activity and a cycling of the clinical states. Treatment includes antiepileptic drug(s) (AEDs) and avoidance of seizure precipitants. Electrophysiological studies are necessary to confirm the diagnosis of nonconvulsive SE and to monitor the response to AED therapy. Prompt recognition and treatment may be necessary to avoid neurological morbidity in select patients. Epilepsy with continuous spikes and waves during slow sleep (ESES) and the Landau-Kleffner syndrome are two rare childhood disorders that are difficult to classify but may be appropriate to include in a discussion of nonconvulsive SE. PMID- 8462491 TI - Systemic effects of generalized convulsive status epilepticus. AB - Generalized convulsive status epilepticus (GCSE) is accompanied by a marked increase in plasma catecholamines. This produces a number of changes in general systemic physiology including hypertension, tachycardia, cardiac arrhythmias, hyperglycemia, acidosis, and hyperpyrexia. If SE is stopped quickly, these changes are self-correcting and do not produce an increased risk of neuropathology. However, if seizures continue, many of the early physiologic changes reverse, and late status epilepticus is marked by hypotension, hypoglycemia, pulmonary edema and a continued acidosis and elevation of body temperature. Prevention of serious hypoglycemia, maintenance of adequate systemic blood pressure to provide adequate cerebral perfusion, and normalizing the body temperature will minimize or prevent neuropathologic sequelae to SE of extended duration. PMID- 8462492 TI - Epileptogenic effects of status epilepticus. AB - Determining whether and under what conditions status epilepticus (SE) leads to undesirable long-term sequelae has major clinical ramifications. In addition to structural brain damage and enduring neurological deficits following SE, it has been suggested that SE can establish a chronic condition of active epilepsy. These three residua (epileptic brain damage, neurological deficits, and epilepsy) have been especially linked to protracted SE. The older clinical literature indicates that these sequelae are especially likely if SE occurs in an immature brain, but this point has been challenged in recent studies. Clinical and animal model work that examines the issue of chronic nervous system deficits arising as a consequence of SE is reviewed, with particular attention to the question of the epileptogenic effect of SE. Because of the inherent problem of not being able to exclude occult neurological disease antecedent to SE in brain, animal model work promises to be especially relevant to the issues at hand. Work done on adult rats has shown that a previously normal brain can be "converted" after a bout of SE to an epileptic brain, as manifest both by epileptic brain damage resembling that found in the hippocampus of patients with intractable temporal lobe epilepsy and by spontaneous recurrent seizures registered in the hippocampus. A two-step model is proposed: morphological brain injury takes place first and this change, in turn, promotes seizures. This model is offered as one way in which chronic active epilepsy can be established by a transient episode of SE. Although some findings from work with animal models have been interpreted as not supporting the idea that the immature brain is sensitive to a chronic epileptogenic influence initiated by SE, the majority of such work is consistent with this idea. On the other hand, a considerable amount of animal work indicates that the brains of immature animals are quite resistant to SE-induced brain damage, in contrast to those of adults. Thus, under these circumstances, a different process of epileptogenesis than the two-step model may be operational. It is concluded that, under appropriate conditions, SE does exert an epileptogenic effect that persists. PMID- 8462493 TI - Treatment of status epilepticus. AB - Status epilepticus, particularly the convulsive form, is a medical emergency, warranting prompt and aggressive treatment. To do this, one must have a thorough understanding of the pharmacology of the anticonvulsant agents. Therapy should be directed toward rapid termination of the status epilepticus, prevention of seizure recurrence, and treatment of any underlying cause. Most importantly, one should establish and adhere to a standard treatment protocol for best results. PMID- 8462494 TI - Coping with a breast cancer diagnosis: a prospective study. AB - Employing the stress and coping theory of Lazarus and Folkman, this study followed 117 women age 40 or over regarding personality, cognitive appraisal, coping, and mood variables before breast biopsy, after diagnosis, and, for those who had cancer, after surgery. Upon biopsy, 36 received a cancer diagnosis, and 81 received a benign diagnosis. The 2 groups did not differ on appraisals, coping, or affect before diagnosis. With prebiopsy affect controlled, cancer patients reported more negative affect postbiopsy than did benign patients. Postsurgery, cancer patients expressed less vigor and more fatigue than benign patients, but the groups did not differ on other negative emotions. Prebiopsy, psychosocial predictors accounted for 54% and 29% of the variance in negative and positive emotion, respectively. Prebiopsy variables also predicted postbiopsy and postsurgery mood; cognitive avoidance coping was a particularly important predictor of high distress and low vigor. PMID- 8462495 TI - The relationship between body weight concerns and adolescent smoking. AB - Although a number of factors have been found to predict smoking status among adolescents, few researchers have examined how belief in smoking as a weight control strategy may be related to smoking in this high-risk population. With the goal of discovering whether belief in smoking as a weight-control strategy predicted smoking status, the present investigation surveyed 659 Black and White high school students. Analyses showed that among regular smokers, 39% of White female and 12% of White male smokers reported using smoking to control their appetite and weight. In contrast, not a single Black male or female reported using smoking to control appetite and weight. Although belief in smoking as a weight-control strategy did not predict regular smokers versus never smokers, the weight-belief item reliably separated experimental smokers from regular smokers. The survey also revealed that White female restrained eaters were the most likely to actually use smoking as a weight-control strategy. PMID- 8462496 TI - Reactivity research on sociodemographic groups: its value to psychophysiology and health psychology. AB - Research on sociodemographic group differences in cardiovascular reactivity has provided support for the potential importance of reactivity as marker-mediator of susceptibility to cardiovascular disease and has facilitated our understanding of the nature of reactivity itself. The article by Treiber et al. in this issue of Health Psychology exemplifies this area of reactivity research. Yet sociodemographic group differences in reactivity and other physiological processes are now in themselves in need of explanation. Thus, the principal scientific challenge facing researchers is the development of testable theoretical models that will facilitate the search for, and ultimate understanding of, the basis for these group differences. This process will not only clarify the determinants of sociodemographic group differences in psychophysiological functioning, but may significantly advance the general understanding of biopsychosocial interactions. PMID- 8462497 TI - Dietary disinhibition, perceived stress, and glucose control in young, type 1 diabetic women. AB - Examining the relationship of stress, dietary disinhibition, and blood glucose control in diabetic young women was the goal of this study. Sixty-five diabetic girls and women, ranging in age from 12 to 26 years, completed eating behaviors and perceived stress scales during regular clinic visits. Blood glucose control was assessed by concurrent glycosylated hemoglobin measurements. Multiple regression analyses indicated that high levels of perceived stress predicted dietary disinhibition and that within the age range studied, young women were more likely than early adolescent girls to perceive their life as stressful. Contrary to previous findings that failed to show that stress can indirectly affect glucose control by interfering with compliance behaviors, the present work indicated a Stress X Dietary Disinhibition interaction in predicting glucose control. Blood glucose control was poorest in those diabetic women who both perceived their lives as stressful and reported medium to high disinhibition. Blood glucose control was unrelated to stress in young women who reported low levels of disinhibition. These results have implications for the development of specific interventions for young diabetic women who perceive their lives as stressful and who may respond to stress by eating. PMID- 8462498 TI - Attributions of responsibility and persuasion: increasing mammography utilization among women over 40 with an internally oriented message. AB - One hundred ninety-seven women over 40 years old and not adhering to national guidelines for screening mammography viewed persuasive messages varying in attributional emphasis (internal, external, or information-only). Internal attributions of responsibility for health-promoting behavior were expected to motivate the greatest change in women's attitudes and behaviors in relation to breast cancer and mammography. Attitudes about breast cancer and mammography were measured immediately and 6 months after the presentation. Twelve months later, women who viewed the internal message were more likely to have obtained a screening mammogram than women assigned to the other 2 conditions. The attributions of responsibility encouraged by the persuasive messages were associated with whether viewing the presentation led to behavior change. PMID- 8462499 TI - Men, family-role quality, job-role quality, and physical health. AB - The relationship between the quality of men's family roles, as spouse and as parent, and the quality of men's job role, on the one hand, and their reports of physical symptoms, on the other, was examined in men drawn from a random sample of 300 dual-earner couples. The main effect of marital-role quality (i.e., rewards and concerns) on physical health was estimated, as was the Marital-Role Quality x Job-Role Quality interaction effect. With respect to the parent role, the effect of both parent-role occupancy and parent-role quality was estimated. After controlling for job-role quality, it was found that parent-role occupancy had neither main nor interactive effects. However, among the men who occupied all 3 roles (n = 180), only parent-role concerns were a significant predictor of physical health reports. Thus, concerns in the parent role are a major unmeasured source of variance in studies of the stress-illness relationship in men. PMID- 8462500 TI - Social support and long-term recovery from coronary artery surgery: effects on patients and spouses. AB - Using a longitudinal design, the effect of social support on recovery from coronary bypass surgery was examined in 155 patients and 103 of their spouses. Perception of the availability of 5 types of social support was relatively stable from preoperation to 1 year after surgery and was significantly related to emotional and functional outcomes. Of the 5 types of support measured, only esteem support was significantly and consistently related to outcomes for patients and spouses. This relationship was strongest within-time, and across time relationships effects were weaker. Spouse's perception of support was related to patient outcomes, controlling for patient perceptions of support. Results suggest that perception of esteem support may be the most salient type of support related to feelings of well-being during and after an acute health-care event. In addition, perception of social support may be characterized by stable individual differences. PMID- 8462501 TI - Ethnicity, gender, family history of myocardial infarction, and hemodynamic responses to laboratory stressors in children. AB - Relationship among ethnicity, gender, grandparents' histories of early myocardial infarction, and hemodynamic responses to forehead cold and treadmill exercise were examined in 87 6-to-8-year-olds (57 White, 30 Black). Boys had greater increases in systemic vascular resistance and decreases in cardiac index to forehead cold. Girls had greater increases and quicker recovery in heart rate to dynamic exercise. Blacks had greater increases and slower recovery in diastolic pressure to exercise and forehead cold. Blacks showed greater increases and slower recovery in systemic vascular resistance to forehead cold. Positive-family history children had greater increases in diastolic pressure and systemic vascular resistance to forehead cold and greater diastolic pressure increases to exercise. Positive-family-history Blacks had greater increases in systolic pressure to exercise and slower recovery than all other groups. PMID- 8462502 TI - Children with persistent feeding difficulties: an observational analysis of the feeding interactions of problem and non-problem eaters. AB - This study examined the relationship between parent's feeding practices and the feeding behavior of toddlers and preschool-age children with (n = 19) or without (n = 29) persistent feeding difficulties. Specifically, patterns of parent-child interaction were assessed during standardized family mealtime observations in the clinic. Parents also kept observational records of their children's mealtime behavior at home and rated the degree of difficulty they experienced in feeding their child during each meal on a daily basis. Observational results showed that feeding-disordered children engaged in higher levels of disruptive mealtime behavior (food refusal, noncompliance, complaining, oppositional behavior, and playing with food) and lower levels of chewing during mealtime. There were several significant age effects, with younger children (under age 3) engaging in more vomiting and less aversive demanding and verbalizations. Parents of feeding disordered children were more negative and coercive in their feeding practices and engaged in higher levels of aversive instruction giving, aversive prompting, and negative eating-related comments. There were several significant associations between coercive parental behaviors and children's food refusal and noncompliance in the sample as a whole. Measures of children's disruptiveness at mealtimes in the clinic were significantly correlated with measures of mealtime behavior in the home. PMID- 8462503 TI - Chronic exposure to an environmental hazard: risk perceptions and self-protective behavior. AB - The risk perceptions and self-protective behavior of 282 immigrant farm workers (all of Mexican origin) in response to pesticide exposure were examined. Several variables were predicted to influence reactions, but some deviations from past studies were expected because cultural or socioeconomic factors could modify risk responses. In keeping with predictions, greater risk perceptions were associated with beliefs that past harm had occurred, future harm to self or offspring was likely, precautions were less effective, and cancer-causing agents were mostly unavoidable. Self-protective behavior was most likely for those receiving risk information, having greater perceptions of control over health and the occupational situation, and believing that precautionary methods were effective. The discussion considers variability in responses to chronic risk and the broader perspective offered by environmental hazard studies. PMID- 8462504 TI - Theory of band broadening for DNA gel electrophoresis and sequencing. AB - The problem of (thermal) band broadening during DNA gel electrophoresis is studied analytically and numerically using the reptation model. It is shown that the orientation of the end-to-end vector of the molecules leads to increased diffusion and even to molecular size-independent band broadening. Thus, the Einstein relation between mobility and diffusion holds for only very small molecules. Also, "self-trapped" molecules are predicted to give fuzzy bands, as observed experimentally. Finally, megabase molecules are discussed and the consequences of our predictions for the improvement of sequencing are considered. PMID- 8462505 TI - Studies on 16 kDa selenium-containing proteins enriched by means of preparative electrophoresis. AB - By in vivo labeling with [75Se]selenite and separation of the proteins in the tissue homogenates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), several selenium-containing proteins or protein subunits were detected in rat tissues (liver, lung, spleen and prostate). Their distribution among the cell components was investigated after fractionation by means of differential centrifugation. The selenium-containing proteins in the 16 kDa range were found to be mainly membrane-bound. By two-dimensional electrophoresis they were resolved into three labeled spots, two with the same relative molecular mass and pI values of about 4.8 and 5.0 and the third with a slightly lower molecular mass and a pI of 4.8. For further investigation they were concentrated and separated from the other labeled compounds by SDS-PAGE using preparative flow through electrophoresis. PMID- 8462506 TI - Consecutive silver staining and autoradiography of 35S and 32P-labeled cellular proteins: application for the analysis of signal transducing pathways. AB - The methodology for the simultaneous analysis of protein synthesis concomitant with protein phosphorylation/dephosphorylation is described. The technique consists of metabolic labeling of rat liver epithelial (RLE) cells with [32P]orthophosphate and [35S]methionine, performing two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) of the mixed samples, followed by silver staining and subsequent autoradiography of the dried silver stained 2-D PAGE electrophoretograms using two films placed back-to-back. The first film, which is positioned in direct contact with the dried silver-stained gel, visualized both exposure to 35S and 32P while the second film recorded exposure to only 32P due to the differential energy levels of the two isotopes. The juxta positioning of the silver-stained images with the two autoradiographic film images permits the unambiguous mapping of the phosphorylated polypeptides back to their corresponding silver-stained and methionine-labeled counterparts. This strategy provides quantitative information utilizing both silver staining (measure of constitutive levels of protein expression) and metabolic labeling to measure rates of protein synthesis and/or degradation and phosphorylation and/or dephosphorylation using [35S]methionine and [32P]orthophosphate, respectively. We have utilized this methodology for the in vitro analysis of transforming growth factor type beta 1 (TGF-beta 1)-mediated signal transduction in RLE cells and have identified three nuclear polypeptides, 1 (pI 4.95/M(r) 97 kDa), 2 (5.00/85 kDa) and 3 (4.90/84 kDa) whose phosphorylation status is rapidly and transiently modulated by TGF-beta 1. The methodology described should have wide applications in studies where it is desirous to measure protein synthesis and/or degradation concomitant with signal transduction pathways involving protein phosphorylation. PMID- 8462507 TI - A comparative two-dimensional gel protein database of the intact and regenerating newt limbs. AB - In this paper we describe a two-dimensional gel database of the regenerating newt limb. Protein synthesis was compared in the intact limb, in the 1-week regenerating limb, representing the dedifferentiation stage, and in the 2-week regenerating limb, representing the formation of the blastema. This comparative database provided data on differential expression of about 800 proteins during the process of limb regeneration. In addition, a map has been generated for these proteins for future guidance in characterizing further new, unknown proteins. The overall expression patterns of the proteins indicated that the dedifferentiation stage was marked by down-regulation of most proteins, while the blastema formation was marked by the appearance of many new proteins. The potential use of such a database in isolating factors involved during limb regeneration is discussed. PMID- 8462508 TI - Comparisons of protein changes in human and rodent hepatocytes induced by the rat specific carcinogen, methapyrilene. AB - There is a growing concern that the rodent bioassay may not always serve as an appropriate model to assess the carcinogenic risk for humans exposed to certain compounds. Mechanistic research that examines the effects of a compound in rodent and man could help in the interpretation of bioassay results. This paper reports a novel use of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) technology to assess similarities and differences in the response of rodents and humans to the rat-specific hepatocarcinogen, methapyrilene (MP). A sequential examination of rodent and human hepatic proteins was conducted following in vivo exposure of rats and mice and in vitro exposure of rat, mouse, and human hepatocytes to MP. Results showed that covalent modifications observed in rats and mice in vivo were duplicated both qualitatively and quantitatively in the corresponding in vitro systems and that these modifications correlated with carcinogenic susceptibility. Covalent modifications in human hepatocytes were minimal despite exposure to concentrations of MP that were 6-fold higher than those used in rodent hepatocytes. These studies suggest that in the case of MP the rat is not the most appropriate model for assessing the human situation. Furthermore, these data show that in vitro-in vivo comparisons based on 2-D PAGE may provide adjunctive information for extrapolating rodent toxicity/bioassay results to human risk assessment. PMID- 8462510 TI - Electrophoretic detection of chitinase isoenzymes using the PhastSystem. AB - Zymographic assays are described for the detection of chitinase isoenzymes following isoelectric focusing. Method 1 used a polyacrylamide overlay gel containing glycol chitin. Following hydrolysis, visualisation of isoenzymes was achieved by fluorescent counter-staining of the gel with Fluorescent Brightener 28. Method 2 used a cellulose acetate membrane overlay which incorporates 4 methylumbelliferyl substrates, hydrolysis of which released a fluorescent product (4-methylumbelliferone). The pIs of chitinase isoenzymes were estimated by using coloured pI markers. A significant time advantage was obtained over previous methods. The method was used to demonstrate chitinase activity in control rat lungs and in rat lungs infected with the pathogen Pneumocystis carinii. PMID- 8462509 TI - Membrane electrophoresis of DNA. AB - We have separated double stranded DNA fragments by electrophoresis using a membrane instead of a gel as separating matrix. Such a membrane, containing separated DNA fragments, is suitable for subsequent hybridization analysis. The method combines electrophoretic separation and transfer onto a solid support and therefore eliminates the need for a transfer or blotting step. PMID- 8462511 TI - Relative efficiency of molecular sieving in solutions of four polymers. AB - The efficiency of size separations of polystyrene sulfate, 120-1085 nm radius, by molecular sieving in polymer solutions, expressed by the separation efficiency function S = M0 magnitude of dKR(R)/dR Te-KR(R)T [where M0 is the mobility in free solution, KR the retardation coefficient, R the geometric mean radius of the particle, KR(R) the retardation coefficient as a function of R, and the polymer concentration is T] increases from methylhydroxypropyl cellulose to polyvinyl alcohol to uncrosslinked polyacrylamide to agarose above its gelling temperature. Separations of DNA, in the size range of 3-21 nm radius, are by at least one order of magnitude more efficient than those of polystyrene sulfate in the size range of 120-1085 nm radius. A plot of S vs. R in the experimental range of T is constructed for the four polymer solutions; this allows one to select optimal media and concentrations for the sieving of particles in the desired range of molecular sizes. PMID- 8462512 TI - Sex identification by polymerase chain reaction of alpha-satellite in aged tissue samples. AB - In vitro amplification of the alphoid repeated sequences clustered in the centromeric regions of the human X and Y chromosomes was carried out. A modification of the amplification conditions reported by Witt and Erickson gave clear amplification bands from 10 pg of genomic DNA template. Results were obtained from the following aged tissue samples: 1 microL three-year-old blood stain, one-year-old single hair roots, six-month-old saliva stains and twelve year-old bone fragments. Good results were obtained even when the template was artificially fragmented into fragments of less than 1 kbp. PMID- 8462513 TI - Separation of cresols using coelectroosmotic capillary electrophoresis. AB - A new method of capillary electrophoresis was established to separate the three cresol isomers. Cresols are of importance due to their use as insecticides, precursors of various dye intermediates, resins, fire-resistant fluids and other purposes. Reversion of the electroosmotic flow was carried out by a polycationic ammonium compound. The separations were carried out at high pH values (pH 12) to obtain complete dissociation of the cresols and short times of analysis (less than 5 min) through fast migration of the cresol towards the anode. Various aliphatic alcohols were added to improve peak shape and resolution. PMID- 8462514 TI - Photopolymerization of polyacrylamide gels with methylene blue. AB - Photopolymerization of polyacrylamide gels in the presence of methylene blue (100 microM) and a redox couple (1 mM sodium toluenesulfinate, a reducer, and 50 microM diphenyliodonium chloride, an oxidizer) has been investigated. The gel point, i.e. the time needed for onset of gelation upon illumination, has been found to lengthen progressively at lower temperatures and at lower light intensities. If the three catalysts are progressively diluted, the gel point does not vary for a threefold dilution, but gelation is greatly hampered below a 1:5 dilution of the three effectors. Photobleaching has been assessed as a function of liquid layer thickness (from 0.5 to 2 mm), of a progressive dye dilution (down to a fourfold dilution) and as a function of temperature. A maximum of elastic modulus is located in correspondence to a minimum of permeability (both situated at 5% cross-linker). It is found that methylene blue-activated polymerization produces polyacrylamide gels with elastic properties which are higher than in persulfate-activated gels, so far the most popular matrices for electrokinetic separations. Due to the ease of preparation, the full control of all experimental parameters, and the lack of oxidizing power of this catalyst system (as opposed to the strong oxidation power of persulfate catalysis), methylene blue catalysis is advocated as a valid alternative to other redox systems. PMID- 8462515 TI - The silver staining procedure of sodium dodecyl sulfate-gels may be accelerated by shortening fixation time. AB - In most silver staining methods the first step in the staining of proteins separated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis is a rather protracted fixation of the gels. Optimum fixation should be short, cause no background staining and effectively immobilize the proteins in the gel without masking the proteins for reaction with the staining solution. Further, the concentration of the fixing compounds should be as low as possible due to the potential toxicity of fixatives. Fixation for only 5 min with mixtures of very low concentrations of formaldehyde and glutaraldehyde in ethanol, or a solution of formaldehyde or glutaraldehyde in picric acid and ethanol, fulfill these demands, provided that the gels were prefixed in ethanol-acetic acid for 10 min. As a consequence of these results a fast and sensitive silver staining procedure is proposed. PMID- 8462516 TI - Gel electrophoresis of giant proteins: solubilization and silver-staining of titin and nebulin from single muscle fiber segments. AB - Giant proteins in the megadalton range (> 0.5 MDa) appear to play important structural and functional roles in striated muscle. Titin (approximately 3 MDa) is involved in the generation of resting tension and the assembly and stability of the sarcomere in skeletal and cardiac muscle tissues, while nebulin (approximately 0.7 MDa) is thought to regulate thin filament length in skeletal muscle. Sodium dodecyl sulfate (SDS)-gel electrophoresis is an important tool in revealing the size, quantity and integrity of these giant proteins in muscle tissues. We report here a method for solubilizing, detecting and quantifying titin and nebulin from short segments of single fibers of the rabbit psoas muscle. Muscle proteins ranging from 15 kDa to 3 MDa were resolved on 3.3-12% gradient polyacrylamide gels that were silver-stained and quantitated by densitometry. Presoaking fiber segments in a low ionic strength pH 8.4 buffer enhances the amount of solubilized titin and nebulin. Solubilizing the presoaked fiber segments with SDS at 60 degrees C for 60 s maximizes the amount of intact titin; solubilizing at higher temperatures causes extensive degradation of titin. Detection sensitivity is sufficient to study titin and nebulin in fiber segments as short as 120 microns. PMID- 8462517 TI - Detection by nile red of agarose gel electrophoresed native and modified low density lipoprotein. AB - The use of nile red to track and stain low density lipoprotein (LDL) and modified LDL in agarose gels was investigated. Lipoproteins were prestained with nile red, a fluorescent dye, prior to electrophoresis. After 2 h of electrophoresis, the LDL and modified LDL were visualized using a UV transilluminator with an excitation wavelength of 302 nm. Spectrofluorometric analysis revealed that the nile red fluorescence of the stained LDL had an emission maximum of 609 nm. This rapid staining method of LDL and modified LDL can detect as little as 2.5 micrograms of LDL protein and permits the immediate visualization of these lipoproteins in agarose gels. PMID- 8462518 TI - Electroblotting of proteins on agarose gel containing specific antibodies. AB - A method is described for electroblotting of proteins, separated by gradient polyacrylamide gel electrophoresis, onto an agarose gel matrix containing specific antibodies. Three proteins of different molecular weight, including human albumin, isolated and in plasma, human plasma transferrin and C3 complement were tested. Immunoblotting on agarose, compared with nitrocellulose, was quantitative and highly sensitive, with small amounts of protein (i.e., 100 pg) being detected. Moreover, albumin aggregates (i.e., dimer, trimer and tetramer) were blotted quantitatively in addition to the monomer, and their percentages were calculated. This method is sensitive, quantitative, reproducible, and includes fewer manipulations; furthermore, it is less expensive and does not require the use of toxic or carcinogenic agents. PMID- 8462519 TI - Semi-dry PhastTransfer detection of biotinylated cell surface molecules. AB - The PhastTransfer system is a semi-dry electrophoretic unit designed to optimize the transfer of small amounts of protein. Because of its efficiency, we adapted the PhastTransfer system for the detection of labeled membrane molecules. Biotin was used as the membrane molecule label because it permitted the long-term storage of labeled lysates as well as the flexibility of derivatizing several different functional groups. After immunoaffinity separation using magnetic microspheres, the protein was electrophoretically separated with the PhastSystem and transferred with the PhastTransfer unit. Using an avidin-linked enzyme amplification system, less than 10 ng of loaded protein could be detected on the transfer membrane. Based on these findings, the PhastTransfer system is a fast, reproducible, and convenient method for the transfer of small quantities of labeled cell surface protein. PMID- 8462520 TI - Gel electrophoresis of an end-labeled DNA. I. Dynamics and trapping in constant fields. AB - A theory for the gel electrophoresis of a flexible polyelectrolyte, bearing an uncharged bulky label or an uncharged section at one end, is presented. We first consider a gel that is fully permeable to the label: we calculate the degree of stretching of the polyelectrolyte and its mobility as a function of chain size, electric field and label friction. Various regimes are identified, and their "existence domains" are calculated. For increasing friction, we predict a transition from a mobility decreasing with chain size to a mobility increasing with chain size. Secondly, we consider the possibility that the label may get trapped at some locations of the gel, a situation relevant to a method of "trapping electrophoresis" recently proposed by Ulanovsky et al. for DNA sequencing. A molecular model for detrapping by thermally activated "backward reptation" is constructed and solved using the Kramers rate-equation theory. Different closed analytical expressions and approximate scaling laws corresponding to different regimes of stretching and field strengths are predicted. The most striking result is a mobility which exponentially decreases past a critical size Np*, which decreases with increasing field. In the regime relevant to the experiments by Ulanowsky et al., we predict Np* approximately E 2/3. The predictions are in good qualitative agreement with presently available experiments, but further experimental investigations are suggested. PMID- 8462521 TI - Immune response to a hapten of fluorescein isothiocyanate in a single mouse analyzed by two-dimensional affinity electrophoresis. AB - Immune response to a hapten of fluorescein isothiocyanate (FITC) in a single BALB/c strain mouse was analyzed by two-dimensional affinity electrophoresis (2D AEP). Anti-FITC antibodies were induced by immunization with FITC-conjugated bovine serum albumin. The antibodies were separated into a large number of spots of IgG due to differences in their isoelectric points(pI) and binding affinities to the FITC ligand. These spots consisted of IgG families which were composed of several spots having an identical affinity to the ligand but a different pI. The spots were not clearly detected in the antiserum taken on day 7 after the primary immunization, but on day 21 the spots of IgG were clearly detected, with a high diversity and specificity for the ligand. The size and number of IgG spots were markedly increased by the secondary immunization; however, the third immunization did not increase the size and number of IgG spots. The IgG spots of each family were specifically stained with an antimouse IgG subclass antibody. Furthermore, a monoclonal antibody (FL-D6) was separated by 2D-AEP into a single family which consisted of seven IgG1 spots having an identical affinity to FITC but different pIs. Therefore, each of the IgG families of anti-FITC antibodies in the antiserum can be generated by a single clone of anti-FITC antibody-producing cells. The substitution of dextran T2000 or lipopolysaccharide for bovine serum albumin as a carrier for FITC induced much smaller amounts of anti-FITC antibodies with a low diversity but high specificity to FITC. PMID- 8462522 TI - Electrophoretic analysis of plant cysteine and serine proteinases using gelatin containing polyacrylamide gels and class-specific proteinase inhibitors. AB - Inclusion of gelatin in polyacrylamide gels provides a sensitive way of detecting multiple proteolytic activities in crude extracts from any source. The present study describes a method allowing discrimination between cysteine and serine proteinases in plant extracts, using gelatin-containing gels in combination with class-specific proteinase inhibitors. Preincubation of extracts with 4 mM phenylmethylsulfonyl fluoride, a serine proteinase inhibitor, or with 25 microM L trans-epoxysuccinyl-L-leucylamido(4-guanidino) butane, a cysteine proteinase inhibitor, allowed the identification of enzymes from both classes in extracts of tomato fruit and papaya latex. The efficiency of the two low molecular weight inhibitors used was very high, and the irreversibility of the inhibiting effect was maintained during electrophoresis conducted in the presence of sodium dodecyl sulfate. The analytic procedure described here, with a detection threshold of less than 100 pg enzyme, is the first that allows quick and accurate discrimination of plant cysteine and serine proteinases separated in electrophoretic gels. This simple and rapid technique could be of interest for studying the evolution of class-specific proteinases in plant extracts during various developmental, physiological, and pathogenic processes. It is also potentially applicable to the majority of eucaryotic and procaryotic systems. PMID- 8462523 TI - Influence of the electrode compartment separating membranes on continuous flow electrophoresis. AB - The influence of the ion permeable diaphragms, separating the electrode compartments of continuous flow electrophoresis chambers from the separation space, are described in detail. A set of equations is derived from a simplified phenomenological model of the ion transport across media boundaries. These equations are useful to predict the magnitude of concentration changes near the membranes due to the electrophoretic ion transport. Adaption to any CFE geometry, membrane material and electrolyte system is possible with only a few measurements, which yield the transference number difference as a characteristic transport property of the membrane material for a special electrolyte. The validity of the equations is checked by experiments. Local electric field strength and local conductivity are measured with a potential gradient conductivity scanner developed in our laboratory. This device yields data on the dynamics of the concentration changes. PMID- 8462524 TI - Can nongenotoxic carcinogens be detected with the lacI transgenic mouse mutation assay? PMID- 8462525 TI - Genotoxicity of volatile and secondary reactive oxygen species generated by photosensitization. AB - Reactive oxygen species were generated in the gas phase by photosensitization involving illumination of Rose Bengal. Depending on whether the chromophore is dry or solubilized, this system produces either energy-transfer reactions leading to generation of singlet oxygen specifically, or a combination of energy-transfer and electron-transfer reactions, providing both singlet oxygen and reduced forms of oxygen, such as superoxide anion and hydrogen peroxide. In neither case were the reactive species mutagenic in strain TA104 of Salmonella typhimurium, which had been previously shown to be reverted by oxygen species generated by the hypoxanthine-xanthine oxidase system in aqueous medium. However, mixed oxygen species induced an increased lethality in a variety of DNA repair-deficient Escherichia coli strains. This genotoxic effect, mainly reparable by the uvrA and recA mechanisms, was efficiently prevented by the thiol N-acetyl-L-cysteine. Singlet oxygen itself failed to exert direct genotoxic effects, although secondary reactants produced by its reaction with cell components enhanced lethality in some repair-deficient bacteria. Distance-dependence analyses provided measurements of the lifetimes of the oxygen species generated in the gas phase. PMID- 8462526 TI - Relative efficiency of Phyllanthus emblica fruit extract and ascorbic acid in modifying lead and aluminium-induced sister-chromatid exchanges in mouse bone marrow. AB - The identification of desmutagens and bioantimutagens in plants has prompted the search for additional plant extracts capable of modifying adverse cellular effects of environmental toxicants. The protective action of crude extracts of Phyllanthus emblica fruits (PFE) against lead (Pb) and aluminium (Al)-induced sister chromatid exchanges (SCEs) was studied in bone marrow cells of Mus musculus. The modifying effect of the crude extract was compared with that of comparable amounts of synthetic ascorbic acid (AA), a major component of the fruits. Oral administration of PFE or AA for 7 consecutive days before exposure of mice to the metals by intraperitoneal injections reduced the frequencies of SCEs induced by both metals. PFE afforded a more pronounced protective effect than AA in counteracting the genotoxicity induced by both Al and Pb: This difference was significant with Pb. The higher protection afforded by PFE may be attributed to the interaction of AA with other natural ingredients present in the crude fruit extract. PMID- 8462527 TI - Formation and characterization of bacterial mutagens from reaction of the alternative disinfectant monochloramine with model aqueous solutions of fulvic acid. AB - Monochloramine has been suggested as an alternative disinfectant to chlorine to reduce levels of trihalomethanes in treated drinking water, but little is known of the toxicological properties and potential health implications of by-products specific to the chloramination process. Model aqueous fulvic acid solutions (200 400 mg C/liter), serving as surrogates for humic surface waters, were chloraminated over a range of molar Cl:C ratios from 1:40 to 1:2. The resulting by-products were extracted into diethyl ether at pH 2 and investigated with the Ames plate incorporation assay. Extractable mutagenicity increased with increasing chlorine and carbon dose up to about 30,000 revertants/liter at Cl:C ratios of 1:2. Mutagenicity was higher in Salmonella typhimurium strain TA100 than in strain TA98, and was decreased in the presence of S9, indicating that the mutagens formed were direct-acting and induced predominantly base-pair substitutions. Bovine serum albumin decreased slightly, and glutathione reduced greatly, the mutagenic activity detected in extracts. HPLC fractionation of the by-products indicated that most of the mutagenic activity was found in the earliest-eluting (most polar) fraction. The mutagenic by-products appeared to be qualitatively similar to 3-chloro-4-dichloromethyl-5-hydroxy-2-(5H)-furanone (MX) in their chromatographic behavior and responses to glutathione and bovine serum albumin, but were less readily detoxified by S9 than was MX. PMID- 8462528 TI - Mutagenicity of iso-butyl nitrite vapor in the Ames test and some relevant chemical properties, including the reaction of iso-butyl nitrite with phosphate. AB - We examined the mutagenicity of iso-butyl nitrite (IBN) vapor and aqueous IBN solution in the Ames test to help evaluate the hazard of sniffing this vapor, a habit which might play a role in the induction of Kaposi's sarcoma associated with acquired immune deficiency syndrome. Chemical analysis showed that the saturated vapor contained 190 micrograms IBN/ml at 25 degrees C, and saturated aqueous solution, 2.6 mg IBN/ml at 21-23 degrees C. When agar plates containing Salmonella typhimurium TA-1535 and rat liver S-9 were exposed to IBN vapor, the number of mutants reached a maximum after 40 min. A mean of 307 mutants/plate (22 x background) was observed when the plates were exposed to IBN vapor for 30 min. Addition of 0.2 ml saturated IBN solution in water to similar plates gave a mean of 179 mutants/plate (7.9 x background) in the absence of S-9, confirming published results. The S-9 did not affect the results. Based on the IBN level in medium exposed to IBN vapor, the vapor was apparently 11 times more mutagenic than IBN solution. This was attributed to continuous replenishment of unstable IBN in the medium by the vapor. The half-life of IBN at 21-23 degrees C was > 1 hr for solutions in water and < 3 min for solutions in the assay medium. This instability was traced to a reaction with phosphate, presumably hydrolysis to nitrite and iso-butanol. IBN in solution was 2.8 times more mutagenic than sodium nitrite, suggesting that IBN was not mutagenic because of its conversion to nitrite. Iso-butanol was not mutagenic. The results demonstrate the potential hazard of sniffing IBN vapor. PMID- 8462529 TI - Base-pair mutations caused by six aliphatic epoxides in Salmonella typhimurium TA100, TA104, TA4001, and TA4006. AB - Salmonella typhimurium strains TA100, TA104, TA4001, and TA4006 were used to detect the base-pair mutations caused by six aliphatic epoxides: chloropropylene oxide, glycidyl 1-naphthyl ether, glycidyl 4-nitrophenyl ether, 1-naphthyl propylene oxide, styrene oxide, and trichloropropylene oxide. Dose-mutagenicity relationships could be established for all six epoxides in strains TA100 and TA104 but not in strains TA4001 and TA4006. These results, together with the lack of sensitivity of the TA100 revertants to DL-1,2,4-triazole-3-alanine, indicate CG-->TA transitions and/or CG-->AT transversions are of major importance for mutations induced by these epoxides in Salmonella TA100 and possibly TA104. In addition, since the reproducibility of the effect of the triazole on TA104 reversions was poor, TA-->AT transversions were not eliminated as also contributing to the mutagenicity of these epoxides in this Salmonella strain. PMID- 8462530 TI - Evaluation of the potential of riddelliine to induce unscheduled DNA synthesis, S phase synthesis, or micronuclei following in vivo treatment with multiple doses. AB - Riddelliine (RID) is a pyrrolizidine alkaloid found in plants of the genera Crotalaria, Amsinckia, and Senecio in the United States. RID has been extensively studied in a wide variety of in vitro short-term genotoxicity tests and has yielded positive responses in most test systems; however, there are fewer data available on the effects of RID in in vivo assays and no data under repeat-dose regimens. We have evaluated the ability of RID to induce unscheduled DNA synthesis (UDS) in hepatocytes, S-phase synthesis (SPS) in hepatocytes, and micronuclei in bone marrow from animals dosed for 5 or 30 days in conjunction with prechronic toxicity testing conducted for the National Toxicology Program. Results of this study indicate that RID did not induce an increase in micronucleated polychromatic erythrocytes (PCE) in bone marrow of mice after 5 days of dosing or in PCE from rats or mice after 30 days of dosing. RID did not induce an increase in UDS in rat hepatocytes after 5 or 30 days of dosing, but it did induce an equivocal UDS response in male mice after both time points and a positive response in female mice after 30 days of dosing. RID induced significant elevations in SPS in rat hepatocytes after both 5 and 30 days of dosing, even at low doses. An increase in SPS was observed in male and female mouse hepatocytes, but only after 30 days of dosing. Rats and mice of both sexes showed a depression in SPS at higher doses. This effect may be a result of toxicity, which compromises the ability of the liver to regenerate. These results demonstrate that repeated administration of test chemicals may alter the genotoxic response to chemicals. PMID- 8462532 TI - Availability of the GENE-TOX database on the National Library of Medicine TOXNET system. PMID- 8462531 TI - Studies for a genotoxic potential of some endogenous and exogenous sex steroids. I. Communication: examination for the induction of gene mutations using the Ames Salmonella/microsome test and the HGPRT test in V79 cells. AB - The mutagenicity results and data of nine progestins (cyproterone acetate, dehydrospirorenone, gestodene, gestonorone caproate, levonorgestrel, norethisterone, norethisterone acetate, norethisterone enanthate, norethynodrel), one hypothetical metabolite (6,7-epoxy-cyproterone acetate), four estrogens (estradiol, ethinylestradiol, cyclodiol, cyclotriol), and four other sex steroids (atamestane, lilopristone, onapristone, propylmesterolone) are reported. All 17 sex steroids were investigated using the Ames salmonella/microsome direct plate incorporation protocol, and seven were additionally tested using the preincubation modification. Seven sex steroids were also studied in the HG-PRT test with V79 cells for the induction of gene mutations in mammalian cells. The metabolite was examined in the Ames salmonella/microsome assay using the standard protocol and the preincubation modification. In all assays the test compounds were investigated up to concentration levels where cytotoxicity and/or visible precipitation occurred or at least the solubility limit of the test compound was reached. For all assays, evaluation of the data indicates that neither any of the sex steroids nor the hypothetical metabolite was able to induce gene mutations whether in the absence or the presence of an extrinsic metabolizing system (S9 mix). PMID- 8462533 TI - Central nervous system symptoms after intravenous lignocaine: dose-response during pregnancy. AB - There is continuing controversy over what dose of what drug should be used to identify an accidental intravascular or subarachnoid catheter placement in obstetric epidural anaesthesia. The purpose of this randomized, double-blind study was to evaluate the dose-effect relationship for the production of central nervous system (CNS) symptoms by intravenous lignocaine. Sixty first-trimester, pregnant patients divided into groups of 10 received saline or one of five doses of lignocaine (0.39, 0.5, 0.63, 0.79, and 1.0 mg kg-1) i.v. An ED95 of 1.12 mg kg 1 was calculated to produce reliable CNS symptoms when injected intravascularly. Lignocaine is an effective and reliable marker for intravenous injection in pregnant women. PMID- 8462534 TI - Effect of intravenous diclofenac on pain and recovery profile after day-case laparoscopy. AB - Diclofenac sodium, 100 mg, or saline was given intravenously after the induction of anaesthesia to 169 patients undergoing outpatient gynaecological diagnostic laparoscopy or laparoscopic sterilization by tubal ligation. Propofol was used as the main anaesthetic agent and fentanyl and paracetamol were given for post operative pain relief. In the post-anaesthesia care unit the amount of analgesics given and the incidence of nausea and vomiting were recorded. The time until oral intake, voiding and walking without assistance were recorded as parameters of recovery and guidelines for discharging the patient. In the diagnostic laparoscopy group, the patients given diclofenac needed significantly (P < 0.05) less fentanyl (25 +/- 33 micrograms, mean +/- SD) and paracetamol (230 +/- 40 mg) for post-operative pain than the patients given saline (fentanyl 47 +/- 53 micrograms and paracetamol 690 +/- 100 mg), which was not the case in the tubal ligation group. However, patients in the tubal ligation group needed significantly more post-operative analgesia than patients in the laparoscopy group. Diclofenac had no influence on the rapidity of recovery or home readiness in either group. It is concluded that diclofenac has no influence on home readiness, but prevents postoperative pain in patients undergoing diagnostic laparoscopies, whereas it was not a potent enough analgesic to prevent pain after laparoscopic tubal ligation. PMID- 8462535 TI - Tiapride versus metoclopramide: comparison after minor gynaecological surgery. AB - Tiapride (Tiapridal, Delagrange), a dopaminergic D2 receptor blocking agent having anxiolytic, sedative, antiemetic and analgesic properties was compared with metoclopramide and placebo in a randomized double-blind trial to determine its effects on post-operative nausea, vomiting, and sedation. The agents were given intravenously immediately before induction of anaesthesia to 75 women scheduled for minor elective gynaecological surgery. A standardized anaesthetic technique was used in all the patients. In the recovery room anti-emetic and sedative effects of tiapride and metoclopramide were similar and significantly better (P < 0.001) than placebo. In the ward at the end of 5 h anti-emetic (P < 0.05), and sedative (P < 0.01) effects of tiapride were significantly better than both metoclopramide and placebo. PMID- 8462536 TI - Intra-individual open comparison of burst-suppression-isoflurane-anaesthesia versus electroconvulsive therapy in the treatment of severe depression. AB - Isoflurane anaesthesia was proposed instead of electro-convulsive therapy (ECT) in patients with treatment-refractory depression. This open study compared burst suppression-isoflurane-anaesthesia (BSIA) and ECT in 12 severely depressed patients. A series of 6 BSIA was administered in every patient. If improvement was insufficient or only temporary, a series of up to 12 ECT was given. A marked improvement of the depression was shown after both BSIA and ECT. Three patients were discharged from hospital after BSIA, nine patients were treated with BSIA and then ECT. The therapeutic effect of both regimens was equal as evidenced by the Hamilton-depression-rating-scale, a visual-analog-scale and the clinical global impression. BSIA requires more time and monitoring than ECT. Our exclusions of coronary, cerebral and peripheral vascular disease, untreated hypertension and focal neurological disease are strongly recommended. Due to the ease of application, ECT remains the standard treatment in depressed patients, but we consider BSIA a valuable alternative at least in patients who object to ECT. PMID- 8462537 TI - Pharmacokinetics of intravenously administered nicomorphine and its metabolites in man. AB - Intravenous doses of 30, 20 and 10 mg nicomorphine (Vilan) are extremely quickly metabolized into the metabolites 6-nicotinoylmorphine and morphine. The half lives of elimination are respectively 3 min for nicomorphine, 3 and 15 min for 6 nicotinoylmorphine, and 135-190 min for morphine. The kinetics of the 30 and 20 mg dose are comparable, the 10 mg dose shows patient dependent variations in metabolism. The AUC of the parent drug and its metabolites is linearly related to the dose. PMID- 8462538 TI - Successful treatment of vasospastic acute ischaemia with intra-arterial nicardipine. AB - Accidental intra-arterial injection of a colouring agent (Bonney's blue) in a 28 year-old male patient induced acute ischaemia of the lower limb, resistant to standard therapy. Its successful treatment was finally obtained by intra-arterial infusion of nicardipine. PMID- 8462539 TI - Thoracotomy wound exploration in a single lung transplant recipient under extrapleural paravertebral nerve blockade. AB - Instillation of bupivacaine through a catheter accurately placed in the extrapleural space prior to closure of a thoracotomy incision provides effective, reliable post-operative analgesia. Its usefulness for further surgery in the post operative period, in this case wound exploration in a lung transplant recipient, is described. PMID- 8462540 TI - Purification and characterization of the major 50-kDa repressor protein from cytoplasmic mRNP of rabbit reticulocytes. AB - A 50-kDa protein has been purified to homogeneity from free mRNP of rabbit reticulocytes. This protein, designated as p50, is present within both free mRNP (approximately 4 mol protein/mol globin mRNA) and polyribosomal mRNP (approximately 2 mol protein/mol globin mRNA). p50 is a basic protein (pI approximately 9.5) and is characterized by a high glycine content of approximately 20%. Nitrocellulose-filter analysis has shown that p50 interacts with globin mRNA with an association constant of approximately 2.5 x 10(8) M-1 (100 mM KAc, 4 degrees C). Various RNA and polyribonucleotides have the following relative affinity for p50; poly(G) > poly(U) > globin mRNA approximately 16S rRNA > poly(A) > poly(C). p50 can be phosphorylated both in vitro and in vivo. PMID- 8462541 TI - Primary structure of N-linked carbohydrate chains of a human chimeric plasminogen activator K2tu-PA expressed in Chinese hamster ovary cells. AB - A recombinant human plasminogen activator hybrid variant K2tu-PA, expressed in Chinese hamster ovary cells, is partially glycosylated at Asn12 (A chain, kringle 2 domain) and completely glycosylated at Asn247 (B chain, protease domain). After release of the N-linked carbohydrate chains by peptide-N4-(N-acetyl-beta glucosaminyl)asparagine amidase F, the oligosaccharides were separated from the protein by gel permeation chromatography, then fractionated by FPLC on Mono Q, followed by HPLC on Lichrosorb-NH2, and analysed by 500-MHz 1H-NMR spectroscopy. The following types of carbohydrates occur: monosialylated diantennary (8%), disialylated diantennary (45%), disialylated tri- and tri'-antennary (1%), trisialylated tri- and tri'-antennary (28%), and tetrasialylated tetra-antennary (18%) structures, all having fucose in alpha(1-6)-linkage at the Asn-bound N acetylglucosamine. Sialic acid occurred exclusively in alpha(2-3)-linkage to galactose, and consisted of N-acetylneuraminic acid (94%), N-glycolylneuraminic acid (3%), and N-acetyl-9-O-acetylneuraminic acid (3%). In addition, glycopeptide fragments corresponding with the A or B chain of K2tu-PA were analysed. The oligosaccharides attached to Asn12 are less processed than those attached to Asn247. Comparison of the glycosylation pattern of K2tu-PA with that of tissue type plasminogen activator from different biological sources showed significant differences. Profiling studies on different K2tu-PA production batches demonstrated that the structures of N-linked oligosaccharides were identical, but that relative amounts vary with the applied isolation procedure of the chimeric glycoprotein. PMID- 8462542 TI - The NMR solution structure of a Kunitz-type proteinase inhibitor from the sea anemone Stichodactyla helianthus. AB - The solution structure of a 55-amino-acid Kunitz-type proteinase inhibitor, ShPI, purified from the Caribbean sea anemone Stichodactyla helianthus, was determined by NMR spectroscopy. Nearly complete sequence-specific 1H-NMR assignments were obtained at pH 4.6 and 36 degrees C, and stereo-specific assignments were determined for 23 pairs of diastereotopic substituents. A data set of 666 upper distance limit constraints and 122 dihedral angle constraints collected on this basis was used as input for a structure calculation with the program DIANA. Following energy minimization with the program OPAL, the average root-mean-square diviation (RMSD) of the 20 DIANA conformers used to represent the solution structure relative to the mean structure is 61 pm for all backbone atoms N, C alpha and C', and 106 pm for all heavy atoms of residues 2-53. This high-quality solution structure of ShPI has a nearly identical molecular architecture as the bovine pancreatic trypsin inhibitor (BPTI), despite a mere 35% of sequence similarity between the two proteins. Exchange rates measured for 48 out of the 51 backbone amide protons showed that the positions of 20 slowly exchanging amide protons correlate well with hydrogen bonds involving these protons in the energy minimized solution structure. The solution structure of ShPI is compared to the four homologous proteins for which the three-dimensional structure is also available. PMID- 8462543 TI - N-carbamoyl-D-amino acid amidohydrolase from Comamonas sp. E222c purification and characterization. AB - N-Carbamoyl-D-amino acid amidohydrolase was purified 119-fold, with 36% overall recovery from a cell-free extract of Comamonas sp. E222c. The purified enzyme was homogeneous as judged by SDS/PAGE. The relative molecular mass of the native enzyme was 120,000 and that of the subunit was 40,000. The purified enzyme hydrolyzed various N-carbamoyl-D-amino acids to D-amino acids, ammonia and carbon dioxide. N-Carbamoyl-D-amino acids having hydrophobic groups served as good substrates for the enzyme. The Km and Vmax values for N-carbamoyl-D-phenylalanine were 19.7 mM and 13.1 units/mg, respectively, and those for N-carbamoyl-D-p hydroxyphenylglycine were 13.1 mM and 0.56 units/mg, respectively. The enzyme strictly recognized the configuration of the substrate and only the D-enantiomer of the N-carbamoyl amino acid was hydrolyzed. The enzyme activity was not significantly affected by N-carbamoyl-L-amino acids and ammonia. The enzyme was sensitive to thiol reagents and did not require metal ions for its activity. The enzyme did not hydrolyze N-carbamoyl-beta-alanine or N-carbamoyl-DL-aspartate suggesting that the enzyme is different from the N-carbamoylamide-hydrolyzing enzymes involved in the pyrimidine degradation pathway. The enzyme did not hydrolyze allantoin and allantoic acid, which are intermediates in purine degradation, N-carbamoylsarcosine and citrulline, suggesting that it is a novel N carbamoylamide amidohydrolase. PMID- 8462544 TI - Possible intermediates in the biosynthesis of mycoside B by Mycobacterium microti. AB - Two lipids were isolated from Mycobacterium microti which became labelled when the cells were grown in the presence of [2-14C]propionate. They were purified by thin-layer chromatography and studied by chemical degradation and mass spectrometry. The lipids were identified as phenolphthiocerol dimycocerosate and phenolphthiodiolone dimycocerosate, the aglycosyl derivatives of mycoside B, the phenolic glycolipid produced by M. microti. Cell-free extracts of the organism were able to glycosylate the lipids to form mycoside B in vitro. It is probable that the lipids are intermediates in the biosynthesis of phenolic glycolipids by mycobacteria. PMID- 8462545 TI - Interaction of ATP analogs with yeast 3-phosphoglycerate kinase. Affinity labeling of the hinge region. AB - Yeast 3-phosphoglycerate kinase is inactivated by incubation with pyridoxal 5' diphospho-5'-adenosine (AdoP2Pxy) [Tamura, J. K., Rakov, R. D. & Gross, R. L. (1986) J. Biol. Chem. 261, 4126-4133). Incorporation of 1 mol affinity label/mol enzyme was sufficient for complete inactivation of 3-phosphoglycerate kinase. The substrate ATP affords substantial protection against inactivation. Partial protection is afforded by the substrate glycerate 3-phosphate. When AdoP2Pxy modified phosphoglycerate kinase was reduced with [3H]NaBH4 and subjected to trypsin hydrolysis, only one radioactive peptide was isolated by reverse-phase high-performance liquid chromatography. The amino acid composition and sequence analysis of the purified radioactive peptide revealed that it spans residues 379 403 of the enzyme and Lys385 specifically reacted with the affinity label. This peptide represents the hinge region between the two domains of the protein, where the active site is also located. The fluorescence intensity of enzyme-bound AdoP2Pxy is enhanced when glycerate 3-phosphate is added, suggesting exposure of the fluorescent probe to a more hydrophobic environment. Another fluorescent analog, anthraniloyl-dATP (ant-dATP), which carries the fluorescent reporter group on the ribose ring, binds to the enzyme at two distinct sites with Kd values of 6 +/- 2 microM and 25 +/- 3 microM, as determined by steady-state anisotropy measurements. Bound ant-dATP was displaced from the enzyme by glycerate 3-phosphate and ATP, as monitored by the fluorescence anisotropy. These results suggest that both fluorescent ATP analogs bind to the active site, which is at the hinge region of the enzyme. Model-building studies showed that when AdoP2Pxy is built into the open form of the enzyme, as described in X-ray studies, the pyridoxyl group of AdoP2Pxy cannot reach Lys385 for Schiff-base formation. Labeled Lys385 is on a beta-turn immediately following helix XII, which was suggested to interact with the nucleotide and become ordered at the active site of 3-phosphoglycerate kinase [Watson, H. C., Walker, N. P. C., Shaw, P. J., Bryant, T. N., Wendell, P. L., Fothergill, L. A., Perkins, R. E., Conroy, S. C., Dobson, M. J., Tuite, M. F., Kinesman, A. J. & Kinesman, S. M. (1982) EMBO J. 1, 1635-1640]. The results presented here suggest that binding of substrates cause significant structural changes in the enzyme. PMID- 8462546 TI - Molecular cloning and expression of the gene for serine hydroxymethyltransferase from an obligate methylotroph Hyphomicrobium methylovorum GM2. AB - The gene encoding serine hydroxymethyltransferase (SHMT), one of the key enzymes of the one-carbon-compound assimilation of a methylotroph, Hyphomicrobium methylovorum GM2, and its flanking regions were isolated using a DNA fragment encoding Escherichia coli SHMT as a probe. Nucleotide sequencing of the recombinant plasmids revealed the SHMT gene codes for the 434-amino-acid protein with a calculated molecular mass of 46,068 Da. The amino-acid sequence of the enzyme showed identity to the sequences of the enzymes from E. coli (55%) and rabbit liver (44%). The recombinant plasmid, which was constructed by ligation of the cloned gene and an expression vector pKK223-3, was introduced to an SHMT deficient E. coli mutant ME5427 (glyA-). The transformed E. coli cells expressed SHMT, which was immunologically and enzymologically indistinguishable from the enzyme isolated from H. methylovorum GM2. PMID- 8462547 TI - Purification, characterisation and crystallisation of selenomethionyl recombinant human interleukin-5 from Escherichia coli. AB - Interleukin-5 (IL-5) plays a key role in the proliferation and differentiation of eosinophils. To aid the solution of the crystallographic three-dimensional structure, we have expressed large quantities of recombinant human IL-5 (hIL-5) in a methionine auxotroph strain of Escherichia coli (DL41) grown on an enriched seleno-DL-methionine-containing medium. Cell densities of A650 = 10 have been achieved. The selenomethionyl-labelled hIL-5 (Se-hIL-5) has been purified and found to contain 3.6 selenium atoms/dimer, and 0.4 methionine residues/dimer. In a B-cell growth factor assay, the Se-hIL-5 is significantly more active than the non-labelled hIL-5. Electrospray mass spectrometry shows two major peaks, with relative molecular masses of 26,326 +/- 6 and 26,280 +/- 8 corresponding to the 4Se and 3Se/1S forms of hIL-5. Unlike the methionine-containing hIL-5, the N terminal selenomethionine is neither oxidised nor carbamoylated and can only be resolved into two species in isoelectric focusing gel electrophoresis. Se-hIL-5 crystallises in the same space group and unit cell as hIL-5. Difference Fourier calculations identify two of the selenomethionines corresponding to Met107 in the dimer. However, the N-terminal is disordered in the crystal, and the N-terminal selenomethionines are not resolved in the difference Fourier. PMID- 8462548 TI - Influence of the immunization against heterologous alcohol dehydrogenase on liver alcohol dehydrogenase isozymes and alcohol abuse of rats. AB - The possible biochemical and immunological mechanisms of the previously discovered phenomenon of significant and prolonged decrease of alcohol abuse of albino rats after the intravenous injection of the heterologous alcohol dehydrogenase (ADH) were studied. It was found that immunization of rats against horse liver S-ADH result in the appearance of a high titre of antibodies against rat liver ADH-3 isozyme. This isozyme is responsible for the metabolism of 90% of alcohol administrated in vivo. It is shown that immunization against horse liver S-ADH leads also to a significant (2--3-fold) lowering of the activity level of ADH-3 in rat liver. The activity level of the other rat ADH isozymes, ADH-1 and ADH-2, was not found to be changed. The intravenous injection of the specific anti-(horse liver S-ADH) serum, purified by affinity chromatography on immobilized horse liver S-ADH, resulted in a significant decrease of alcohol abuse in alcohol-dependent animals. These results allow us to assume an important role of rat liver ADH-3 in the mechanism of alcohol addiction. PMID- 8462549 TI - Removal of N-terminal formyl groups and deblocking of pyrrolidone carboxylic acid of proteins with anhydrous hydrazine vapor. AB - Many proteins have a blocked alpha-amino group which renders them inaccessible to sequence analysis by the classical Edman degradation procedure. Blockage typically occurs when the alpha-amino groups are acylated with acetyl or formyl groups or when the N-terminal residue is pyrrolidone carboxylic acid formed by cyclization of glutamine. We have found that N-formyl groups of proteins and peptides can be removed by exposure to hydrazine vapor at -5 degrees C for 8 h. Under these conditions, peptide-bond cleavage or modification of the constituent amino-acid residues does not occur. Deblocking of N-terminal pyrrolidone carboxylate residues by conversion to gamma-hydrazidyl glutamic acid can be achieved by exposure to hydrazine vapor at 20 degrees C for 4 h. These conditions cause partial modification of asparagine and glutamine residues to their corresponding hydrazides, and conversion of arginine residues to ornithine. PMID- 8462550 TI - The sum of the control coefficients of all enzymes on the flux through a group transfer pathway can be as high as two. AB - In simple metabolic pathways the control exerted by enzyme concentrations on the pathway flux adds up to one when the control is quantified in terms of control coefficients. In this paper we demonstrate that this classical summation theorem has to be modified in pathways where the enzymes participate by transferring a group between each other. We derive the corresponding new control theorem and show how it is consistent with standard metabolic control analysis. In group transfer pathways lacking enzyme complexes, the sum of the flux control by enzyme concentrations and by the donor and acceptor couples of the pathway, equals two. In group-transfer pathways with enzyme-enzyme interactions the flux control by the dissociation rate constants of the enzyme-enzyme complexes must be added to obtain this sum of two. In all cases, the sum of the controls by all reaction activities remains one. Both by using the new theorem and by numerical simulations, we then demonstrate that, in group-transfer pathways with or without enzyme interactions, the sum of the control of enzymes on the pathway flux is higher than one and can reach a value of two. The total control of all enzymes on the concentration of any intermediate either with or without the transferred group can be equal to one, rather than to the zero found in the classical case. Examples of group-transfer pathways are the bacterial phosphoenolpyruvate:sugar phosphotransferase system, the main pathway for uptake of sugars in Enterobacteriaceae, and the electron-transfer chain in free-energy transducing membranes. PMID- 8462551 TI - Structural studies of the O-antigenic polysaccharide of Fusobacterium necrophorum. AB - The O-specific polysaccharide component of the lipopolysaccharide produced by Fusobacterium necrophorum is of the teichoic acid type, with repeating units connected by phosphoric diester linkages. Dephosphorylation of the polysaccharide by treatment with aqueous hydrogen fluoride yielded a carbohydrate composed of a trisaccharide linked to an acidic component. This product, and the polysaccharide, were investigated by chemical methods and 1H-, 13C-, 31P- and 15N NMR spectroscopy and the former also by fast-atom-bombardment mass spectrometry. It is proposed that the polysaccharide is composed of repeating units having the following structure, in which Fuc represents fucose (6-deoxy-galactose), Am represents an acetamidino group and Sug 2,4-diamino-2,4,6-trideoxy-D-glucose ('bacillosamine') acetylated at the 2-position and acylated with a (S)-3 hydroxybutanoic acid at the 4-position. The acid was identified as a 2-amino-2 deoxy-2-C-methyl-pentonic acid (2-amino-2-methyl-3,4,5-trihydroxypentanoic acid). The configuration of this acid remains to be determined. [formula: see text] PMID- 8462552 TI - pH-induced structural transitions of bovine serum albumin. Histidine pKa values and unfolding of the N-terminus during the N to F transition. AB - 1. Titration curves have been constructed for all the resolvable resonances of defatted bovine serum albumin [pH meter readings in 2H2O solution (pH*) 2-10], including complete curves for six His residues and partial curves for a further four. Three His residues have unusually low pKa values (less than 5.5). 2. Abrupt discontinuities in the titration curves of nearly all resonances were observed near pH 4.3 (N to F transition), together with a marked loss of chemical shift dispersion at low pH*. No such loss of dispersion occurs in the high pH region previously associated with the N to B transition (approximately pH 8). The NMR data provide strong evidence that the N to F transition is not localised in domain III as had been previously suggested. 3. A localised unfolding of the N terminal region occurs below pH* 4.5. PMID- 8462553 TI - Taking enzyme kinetics out of control; putting control into regulation. AB - The matrix formulation of metabolic control analysis, which states that multiplying the elasticity matrix for any system by the corresponding control matrix yields an identity matrix, can be transformed into a statement that multiplying a matrix expressing internal regulatory properties by a matrix expressing external regulatory properties also yields an identity matrix. This transformation supplies the formal basis for metabolic regulation analysis, and provides the key to determining the control structure of a system without the need to know the exact changes in enzyme activities that are made to measure control coefficients. PMID- 8462554 TI - Isolation and chemical characterization of a novel insulin-related neuropeptide from the freshwater snail, Lymnaea stagnalis. PMID- 8462555 TI - Mechanistic studies on rhodopsin kinase. Light-dependent phosphorylation of C terminal peptides of rhodopsin. PMID- 8462556 TI - Urinary tract infection with Corynebacterium urealyticum in South Africa. AB - Corynebacterium urealyticum has been well documented as a urinary pathogen in Europe. The purpose of this study was to investigate the incidence and clinical relevance of Corynebacterium urealyticum as a urinary pathogen in a predominantly Third World population (South Africa) and to attempt to increase the isolation rate by culturing urine specimens on a selective medium. Two methods were used to isolate Corynebacterium urealyticum from urine specimens. Blood agar plates from routine urine cultures of 7,912 urine specimens were incubated for 48 hours and 1,281 specimens were cultured on a selective medium as well as on routine media. The antimicrobial susceptibility of all isolates of Corynebacterium urealyticum was tested. The yield of Corynebacterium urealyticum on blood agar was three isolates in three patients (0.038% of 7,912), all of whom had pyuria, alkaline urine and risk factors for Corynebacterium urealyticum infection. Use of selective media increased the yield of Corynebacterium urealyticum to 15 of 1,281 specimens (1.17%), however 73% of these urine samples yielded other pathogens and none had an alkaline pH which could not be attributed to the presence of another urealytic pathogen. All isolates were susceptible to vancomycin and 92.6% susceptible to norfloxacin. The pathogenic potential of Corynebacterium urealyticum was confirmed in South African patients, but the incidence of infection was low. The use of a selective medium is therefore not cost-effective in all cases but could be used selectively on the basis of typical urine findings and patient criteria. PMID- 8462557 TI - Rapid detection of Shigella dysenteriae and Shigella flexneri in faeces by an immunomagnetic assay with monoclonal antibodies. AB - A rapid and sensitive method for the detection of Shigella dysenteriae type 1 and Shigella flexneri serotypes in faeces based on capture of the bacteria with immunomagnetic particles is described. The particles were coated with either of two different monoclonal antibodies specific for the O-antigens of Shigella dysenteriae type 1 and Shigella flexneri serotypes. Captured bacteria were detected by an enzyme immunoassay with O-antigen specific rabbit antiserum. The whole assay required 2 to 3 hours to perform and the sensitivity limit was 10(3) cfu/ml as determined by viable cell counting. One hundred and fifty enterobacteria strains, including 100 Shigella strains from a strain collection, and 302 fresh faecal samples were used for the study. All Shigella dysenteriae type 1 and Shigella flexneri culture-positive faecal samples were positive in the immunomagnetic assay. In addition 18 of 252 culture-negative faecal samples were positive. The immunomagnetic assay was compared with latex agglutination and indirect immunofluorescence using culture as the reference method. The immunomagnetic assay had a sensitivity of 100%, latex agglutination a sensitivity of 72% with 28% false-negative results, and indirect immunofluorescence a sensitivity of 95%. The immunomagnetic assay was superior in sensitivity since it also detected Shigella in faecal samples up to two days after antibiotic therapy had been started, which both latex agglutination and indirect immunofluorescence failed to do. The high sensitivity in detecting live and dead bacteria, and the ease of performance of the immunomagnetic assay render it an attractive method for detection of Shigella. PMID- 8462558 TI - Acute lower respiratory tract infection associated with Chlamydia pneumoniae in Germany. AB - Serum specimens from 223 patients with acute lower respiratory tract infection were examined for antibodies to Chlamydia pneumoniae using the microimmunofluorescence test. Antibodies to Chlamydia pneumoniae were detected in 18 (20%) of 91 children and 64 (48%) of 132 adults. Among those individuals, 4 (4%) children and 15 (11%) adults had elevated IgG antibody titres indicating acute or recent infection. Specific IgM antibodies were observed in two patients. These results suggest that a significant proportion of lower respiratory tract infections in Germany is caused by Chlamydia pneumoniae. PMID- 8462559 TI - Acute meningoencephalitis as the sole manifestation of Q fever. AB - The case of a 25-year old man who presented with meningoencephalitis as the sole clinical manifestation of Q fever is described. Serological studies revealed the presence of IgM and IgG antibodies to Coxiella burnetii. The patient responded favourably to a ten-day course of i.v. ceftriaxone and was discharged without any neurological sequelae. PMID- 8462560 TI - Invasive infection with Mycobacterium genavense in three children with the acquired immunodeficiency syndrome. AB - Three children with human immunodeficiency virus infection and invasive infection with Mycobacterium genavense are reported. Fever spikes, abdominal cramps and distension, diarrhea or ileus, and anemia were the predominant symptoms in the severely immunodeficient patients (CD4 lymphocytes < 0.04 x 10(9)/l). Numerous acid-fast bacilli were readily detectable by microscopy in stool samples and in lymph node biopsies, but cultures for mycobacteria remained negative. Mycobacterium genavense should be sought when invasive non-tuberculous mycobacteriosis is suspected and mycobacterial cultures from blood or other sites show limited growth. Multiple-drug regimens including amikacin, ethambutol, rifampin, and clarithromycin may be of benefit in controlling the infection, as observed in two patients. PMID- 8462561 TI - Three cases of varicella thrombophlebitis as a complication of varicella zoster virus infection. AB - Three cases of deep venous thrombosis following varicella infection are described which were successfully treated with bed rest and anticoagulants. Two of these patients had severe pulmonary manifestations of varicella and the third was complicated by pulmonary embolism. Deep vein thrombosis is an uncommon systemic manifestation of varicella, possibly associated with vascular endothelium wall damage caused by varicella zoster virus infection. PMID- 8462562 TI - Characterization of penicillinase-producing strains of Neisseria gonorrhoeae. AB - Twenty-three penicillinase-producing strains of Neisseria gonorrhoeae were characterized. All strains showed hybridization with a TEM-1 probe and production of a TEM-1 type beta-lactamase (pI 5.4) on isoelectric focusing. Eight strains also showed a beta-lactamase band of pI 5.5. The penicillin MICs for the strains producing only TEM-1 were in the range 4-16 micrograms/ml; MICs of the strains with the additional pI 5.5 band were > or = 128 micrograms/ml for seven strains and 4 micrograms/ml for an arginine-hypoxanthine dependent strain. The association of the high MICs with the presence of the pI 5.5 band was statistically significant. The pI 5.5 band could represent a new beta-lactamase type or a TEM-1 mutant. PMID- 8462563 TI - In vitro susceptibility of quinolone-resistant Campylobacter jejuni to new macrolide antibiotics. AB - The MICs of erythromycin and three new macrolide antibiotics were determined for 36 quinolone-susceptible and 106 quinolone-resistant Campylobacter jejuni. The MIC90 values of azithromycin, clarithromycin, roxithromycin and erythromycin were 0.5, 4, 16 and 4 mg/l respectively. No difference was found between macrolide activity against the quinolone-susceptible and the quinolone-resistant strains. Clarithromycin and especially azithromycin might eventually replace erythromycin for the treatment of Campylobacter jejuni infections in view of their pharmacological properties. PMID- 8462564 TI - Evaluation of a rapid latex test for direct detection of Streptococcus agalactiae in various obstetrical and gynaecological disorders. AB - Cervical samples collected during speculum examination in 413 women were tested for the presence of Streptococcus agalactiae by Gram staining, a new latex agglutination test and standard cultures. The results of each method are reported in correlation with the clinical circumstances of isolation. Gram stain and the latex agglutination test had a sensitivity of 30% and 78%, and a specificity of 89% and 98% respectively compared with culture. The sensitivity of the latex agglutination test was higher in cases of premature rupture of membranes (90%), presumed chorioamnionitis (86%), presumed post-partum endometritis (86%) and presumed salpingitis (87%). This latex agglutination test appears to be useful for identifying patients who are heavily colonized with Streptococcus agalactiae and are at a high risk of infection. PMID- 8462565 TI - Two cases of Actinomyces pyogenes infection in humans. AB - Few confirmed human cases of Actinomyces pyogenes infection have been reported partly because of inadequate identification of this bacterium. In this study, two new cases are reported with emphasis on the characteristics which are relevant for identification of the isolates. A review of previously reported cases is presented. PMID- 8462566 TI - Association of hepatitis B and human immunodeficiency virus infections in Tanzanian population groups. AB - A study was performed to determine whether there is a correlation between hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection in population groups in the Dar es Salaam area in Tanzania where HBV infection is endemic. A panel of 460 sera from army recruits, health personnel and pregnant women was tested. In the whole group seromarkers of HBV infection were found in 61.9% of 134 HIV positive subjects versus 51.5% of 326 seronegative subjects, a difference which was not statistically significant (p > 0.05). In the group of pregnant women, however, 66.7% of 120 HIV positive subjects had markers of HBV infection versus 49.0% of the 157 HIV seronegative subjects (p < 0.01). This shows that a considerable proportion of young females are also exposed to HBV at the time they acquire HIV infection. PMID- 8462567 TI - Pasteurella stomatis infection following a dog bite. PMID- 8462568 TI - Spontaneous peritonitis due to Brucella melitensis in a patient with cirrhosis. PMID- 8462569 TI - Frequency of plasmid-mediated beta-lactamases in Enterobacteriaceae isolated in Spain. PMID- 8462570 TI - Killing kinetics of vancomycin and rifampin tested alone and in combination against penicillin-resistant Streptococcus pneumoniae. PMID- 8462572 TI - Radiologic diagnosis of pseudoaneurysms complicating pancreatitis. AB - Angiographic and computed tomographic (CT) examinations in five patients with arterial pseudoaneurysms complicating pancreatitis were evaluated retrospectively. Selective arteriography was superior to CT imaging in demonstrating pseudoaneurysm formation. However, angiography was performed in four patients after a CT study considered suspicious for a pseudoaneurysm; none of these four patients had clinical evidence of bleeding. Correlation with surgical findings was established in four patients, indicating that pseudoaneurysms complicating pancreatitis were not located within a pancreatic pseudocyst. Some thrombus-containing pseudoaneurysms may present with a pseudocyst appearance on CT images. PMID- 8462573 TI - Artifacts in the ascending aorta on computed tomography: another measure of aortic distensibility? AB - The appearance of the ascending aorta was studied in 53 patients undergoing computed tomography on a modern system capable of routine 1 second data acquisition times. Motion artifact caused a blurred aortic outline in 48 patients; the extent was objectively and subjectively assessed. The maximum and minimum cross-sectional aortic areas were measured at the margins of the blur. The area of the blur, expressed as a fraction of the minimum aortic cross sectional area, decreased with age (P < 0.001) and was significantly smaller in the 13 patients with known cardiovascular problems (P < 0.05). These findings were substantiated by the subjective gradings which showed less marked artifacts amongst elderly patients (although this observation did not reach statistical significance). Artifacts were less prominent in 16 patients with evidence of aortic wall calcification, both on subjective grading (P < 0.05) and formal area measurements (P < 0.05). These observations lead us to believe our postulation that this artifact is an indicator of aortic distensibility and thus, indirectly, of cardiovascular status. PMID- 8462571 TI - Influence of selective decontamination of the digestive tract on microbial biofilm formation on endotracheal tubes from artificially ventilated patients. AB - The effect of selective decontamination of the digestive tract on the nature and incidence of microbial biofilm formation on endotracheal tubes was assessed. Thirty endotracheal tubes were obtained post-extubation from patients in the intensive care unit who had been ventilated for a 1 to 15 day period and who did or did not receive the antibiotic regimen. Extensive biofilm formation was identified by scanning electron microscopy on 97% of tubes examined. Endotracheal tube biofilm in tubes obtained from patients who received selective decontamination of the digestive tract showed a high prevalence of colonization with yeast (4 of 15 tubes) and gram-positive bacteria (streptococci, staphylococci and diphtheroids) (14 of 15 tubes). Staphylococcus aureus was isolated only from this group. Pseudomonas spp. were isolated from 2 of 15 tubes in both patient groups. Enteric gram-negative organisms (coliforms, Klebsiella and Proteus spp.) were isolated only from tubes of patients who did not receive the antibiotic regimen (4 of 15 tubes). Yeasts, however, were not isolated from these tubes. Group D streptococcal isolates were resistant to tobramycin as were half of the Staphylococcus aureus isolates. For gram-negative bacteria, the MIC of tobramycin was in the range 1-64 micrograms/ml and the MIC of polymyxin in the range 0.5-16 micrograms/ml. Although a reduction was observed in the incidence of gram-negative microorganisms, this antibiotic regimen does not inhibit biofilm formation on the endotracheal tube by other pathogens associated with pneumonia in ventilated patients. This persistent nidus may be a factor in the pathogenesis of nosocomial pneumonia. PMID- 8462574 TI - CT findings in unusual inflammatory masses of the parotid gland. Report of four cases. PMID- 8462575 TI - Benign tumors of the small intestine: preoperative evaluation with a barium infusion technique. AB - During a seven year period 18 benign small intestinal tumors were histologically documented in patients referred to us for a small bowel study, using a barium infusion technique. These included seven leiomyomas, five adenomatous polyps, two Peutz-Jeghers hamartomas, one myoepithelial hamartoma, one lipoma, one Brunner's gland adenoma and one neurilemmoma. Ten of the patients were women and eight were men, with their ages ranging from 20 to 75 years (mean age 45 years). Presenting symptoms were gastrointestinal bleeding in 12, anemia in 9, abdominal pain in 4, partial intestinal obstruction in 3 and bloody diarrhea in one. The time elapsed from onset of symptoms to radiological diagnosis ranged between one month and seven years (mean time 16 months). Multiple lesions were encountered in four cases and solitary in fourteen. The site of involvement was the duodenum in 3 patients, the jejunum in 8 and the ileum in 7 of them. Main radiological appearances included solitary or multiple intraluminal filling defects, mass effect on neighbouring loops and dilation of intestinal loops proximally to the lesion. The primary tumor, in the form of a mass or other abnormality of the small intestine was identified in all study cases. Correlation with surgical or endoscopic findings showed that radiology depicted all single lesions, whereas multiple lesions were underestimated in one case. The individual morphological changes shown on examination of the resected specimens resembled the appearances on the barium study in all cases. However, enteroclysis missed four out of seven ulcers and a stalk in one of the five pedunculated lesions. A specific tumor-type diagnosis was reached preoperatively in eleven patients, it was suggestive in five and mistaken in two of them. Our experience indicates that enteroclysis is an effective means in evaluating patients with suspected benign small bowel tumors, preoperatively. PMID- 8462576 TI - The value of MRI in the evaluation of the ACL deficient knee and in the post operative evaluation after ACL reconstruction. AB - To evaluate the usefulness of magnetic resonance imaging (MRI) in the exploration of the anterior cruciate ligament (ACL) deficient-knee, a total of twenty-five patients with chronic instability of the knee joint and who underwent both MRI and arthroscopy were studied prospectively. Twenty-three of these patients underwent an intra-articular reconstruction of the ACL with bone-patellar tendon bone autografts. For the ACL lesions MRI had a sensitivity of 95.8%, a specificity of 100% and a diagnostic accuracy of 97.7%. Associated bowing of the PCL was seen in 20 cases of the study group. For the associated meniscal lesions MRI had a sensitivity of 77.7%, a specificity of 94.7% and a diagnostic accuracy of 91.5%. In no case did MRI allow to detect the minimal cartilage irregularities observed in the arthroscopy. MRI had great accuracy for the evaluation of the anchoring points, direction of the tunnels and the state of the autografts at intra-articular level. It is concluded that MRI is a useful imaging diagnostic modality for evaluation of the ACL deficient-knee and the intra-articular reconstruction of the ACL, thereby MRI affords the surgeon better preoperative planning. PMID- 8462577 TI - Mesoinnominate shunt for the treatment of Budd-Chiari syndrome: evaluation with multimodality imaging. AB - The construction of a mesoinnominate shunt between the superior mesenteric vein and the left innominate vein is a recent surgical procedure for the treatment of Budd-Chiari syndrome with vena caval obstruction. The purpose of this study was to determine the role of the different imaging modalities for the follow-up of mesoinnominate shunts. Doppler US (n = 32), and MR imaging examinations (n = 32) were prospectively performed in 10 patients with mesoinnominate shunts. Shunt patency or thrombosis was confirmed with angiography (n = 32) and transhepatic portography with pressure measurement (n = 6). For each follow-up evaluation, all examinations were performed within 4 days. Shunt patency was correctly demonstrated in 28/28 cases with Doppler US, CT and MR imaging. Shunt thrombosis was correctly demonstrated in 4/4 cases with Doppler US, CT and MR imaging. Since Doppler US, CT and MR imaging have the same accuracy for diagnosing mesoinnominate shunt patency and detecting thrombosis, our study suggests that redundant screening methods can be avoided. Doppler US is accurate enough and should be the preferred technique in the evaluation of mesoinnominate shunts. PMID- 8462578 TI - Visualization of basal pleural space and lung with advanced multiple beam equalization radiography (AMBER). AB - During clinical use of AMBER (Advanced Multiple Beam Equalization Radiography) it was frequently felt that the basal lung and pleural space were better appreciated than with standard chest radiography. We aimed to quantify the amount of additional relevant anatomy seen in this part region and to review the normal radiographic anatomy. Four hundred patients without known chest disease were evaluated. Two groups of 200 patients (50% female) were studied with either AMBER or standard chest radiography (140 kVp, 180 cm FFD, Kodak Tmat G film, Lanex regular screen; for both techniques). Visualization of the pleural sinuses (in percent of the transverse thoracic diameter) and the basal pulmonary vessels (4 point scale) was evaluated by a panel of 3 radiologists. The shape of the sinus was traced if sufficiently visible and subjectively evaluated. A significantly (P < 0.05) larger segment of the dorsal (41 +/- 34%) and ventral (14 +/- 15%) sinuses was seen with the AMBER technique than with the standard technique (16 +/ 21% and 9 +/- 11%, respectively). Vessel visibility was also significantly (P < 0.001) better with AMBER (3.2 +/- 0.6) than with the standard technique (1.9 +/- 0.6). The dorsal sinus showed alternatively a curved or pointed configuration. PMID- 8462579 TI - The reliability and value of determining mediastinal involvement and width on chest radiographs in patients with Hodgkin's disease. AB - Over the years several methods for evaluating mediastinal involvement in Hodgkin's disease have been applied to chest radiographs and conflicting results have been reported. In a retrospective study of 104 patients we evaluated interobserver variability in assessing mediastinal involvement and investigated various cut-off points for mediastinal size as to their ability to identify patients with high- and low-risk for recurrence. For mediastinal involvement the concordance rate for two reviewing radiologists was 94% (98/104) and compared with prior assessment by outside radiologists the concordance rates were 90% (94/104) and 88% (92/104), respectively. A good correlation between the reviewing radiologists was found for the quantitative evaluation of mediastinal diameter and thoracic ratios. ROC curves and relative risk figures were used to investigate the various cut-off points for mediastinal width and for the ratios of the maximal mediastinal diameter to the chest diameter at Th 5-6 (M1) and to the chest diameter at the widest thoracic level (M2). Neither the ROC curve analysis nor the use of relative risk figures revealed a cut-off point clearly more accurate in predicting recurrence. In conclusion, our results do not suggest that interobserver variability in mediastinal assessment, differences in the method of mediastinal measurement, or the cut-off points applied to mediastinal width can explain the discrepancies in the reported data on the prognostic value of mediastinal width in Hodgkin's disease, but rather factors such as patient selection and differences in treatment given may be responsible. PMID- 8462580 TI - Epidural and subdural contrast in myelography and CT myelography. AB - A retrospective study of 624 lumbar myelographic and CT myelographic procedures was undertaken to evaluate the frequency, radiographic and clinical relevance of contrast medium outside the dural sac. Our findings indicate that epidural contrast is frequently identified on CT scans with highly sensitive window settings (in 35.4% of all CT myelographic studies). Standard myelographic films are less sensitive for the detection of epidural contrast (9.6%). Subdural contrast is far less often encountered (in 2.4% of CT myelographic studies and in 3.2% of standard myelographic films). We believe leakage of contrast to occur through the puncture site into the epidural and subdural space. PMID- 8462581 TI - Diffuse intrahepatic periportal plexiform neurofibroma. PMID- 8462582 TI - Chest "gestalt" and detectability of lung lesions. AB - Image perception in chest radiography is thought to occur on two levels, (a) a fast global response based on learned templates ("gestalt") and, (b) a slower systematic scan process. The relative importance of "gestalt" on the detection of nodular lung cancers was studied by disturbing the "gestalt" through rotation of the radiograph but not actually diminishing the image content available for viewing. Sixty chest radiographs (20 normals, 21 with subtle lung cancers, 19 with obvious lung cancers) were presented to three readers in normal and abnormal (rotated randomly in 90 degree increments) orientation for varying durations (0.25 s, 1 s, 4 s and unlimited viewing time). The results indicate that the detectability of obvious and subtle lung lesions was degraded by the disturbed "gestalt" for both short and long viewing times. The readers did not significantly increase their unlimited viewing time when faced with rotated images (4.4 +/- 3.4 s) as opposed to non-rotated images (4.0 +/- 3.2 s). We conclude that the detection of lung lesions relies heavily on the chest "gestalt" and that systematic scanning cannot fully compensate for an impaired global response due to a disturbed "gestalt." PMID- 8462583 TI - Pediatric bronchography performed through the flexible bronchoscope. AB - Ten children, ranging in age from 2 months to 16 years, were evaluated by bronchograms performed during bronchoscopy. Nine of the ten children had significant pathology demonstrated by the bronchogram that elucidated findings unclear from other imaging procedures at the time of bronchoscopy. Despite the generally negative opinions about the utility of bronchograms in children, information obtained by bronchography can be quite useful. Bronchography during bronchoscopy proved to be quick, simple, and safe. PMID- 8462584 TI - Unusual cystic liver lesions: a pictorial essay. AB - Cystic liver lesions are being increasingly detected by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). These lesions produce a wide spectrum of radiological features. Unfortunately their appearance is not always specific and they may resemble and be mistaken for other lesions. Cystic lesions can be classified into congenital, inflammatory, neoplastic and miscellaneous groups. In this pictorial essay a number of unusual cystic lesions are illustrated with a brief analysis of morphological features of the individual lesion and a diagnostic approach for cystic liver lesions is suggested. PMID- 8462585 TI - The functional effects of gadolinium-DTPA on the isolated perfused rat kidney. AB - Clinical experience suggests that Gd-DTPA has no deleterious effect on renal function. We have evaluated the effects of a large dose (0.6 ml/kg body weight) of this contrast agent on the function of the isolated perfused rat kidney. Gd DTPA led to a mild, transient increase in glomerular filtration rate with no subsequent fall during the 30 minute observation period. However, Gd-DTPA induced an increase in renal vascular resistance (+ 10%, P < 0.05) as a mild decrease in renal perfusate flow was observed during the experimental phase when compared to that of control kidneys. No significant effect was demonstrated on the fractional excretion of albumin or the fractional reabsorption of sodium. These data support, in an ex vivo experimental model, the clinical experience of the safety of this paramagnetic contrast agent in relation to renal function. PMID- 8462586 TI - Relaxation time changes of the uterus during the menstrual cycle: correlation with hormonal status. AB - Six women volunteers underwent pelvic MR imaging at 0.02 T four times during their menstrual cycle. The T1 and T2 relaxation times of the myometrium and endometrium were measured and correlated with the serum estradiol and progesterone levels. The magnitude of the relaxation times were highly individual but the pattern of their variation during the menstrual cycle was similar. The relaxation times were shortest at the beginning and end of the cycle. The most rapid increase occurred during the proliferative phase, followed by little or no increase through to the middle of the secretory phase. The T1 and T2 times of the endometrium correlated directly with the serum estradiol levels during the entire menstrual cycle (r = 0.5, P = 0.02) and the T2 times of the endometrium with the serum progesterone levels during the secretory phase (r = 0.6, P = 0.05). The correlation between the relaxation times of the myometrium and the serum hormonal levels was poor. The results indicate that the relaxation times of the myometrium and endometrium vary during the menstrual cycle reflecting the serum hormonal status. MR imaging of the uterus with relaxation time measurements may be clinically useful to examine the menstrual cycle and its pathology. PMID- 8462587 TI - Posttransplant renal artery stenosis--outpatient intraarterial DSA versus color aided duplex Doppler sonography. AB - A prospective trial was conducted to assess the accuracy of color aided duplex Doppler (CADD) sonography to rule out transplant renal artery stenosis (TRAS) and to determine feasibility and safety of intraarterial digital subtraction angiography (DSA) in hypertensive renal allograft recipients on an outpatient basis. All patients were hypertensive (n = 18, mean age: 42 +/- 11 years) and underwent CADD and an i.a. DSA with 4F catheters. There was a 4 hour rest post DSA. Duplex Doppler measurements of maximum velocity were obtained. Absolute values of > or = 100 cm/s were considered indicative to suspect TRAS. DSA revealed severe TRAS in 4 patients (22%). The stenoses were located near the iliorenal anastomosis (n = 2) and at the bifurcation of the renal artery (n = 2). Duplex Doppler classified twelve (67%) renal artery pedicles normal (maximum velocity: 79 +/- 23 cm/s). TRAS was suspected in 6 patients with a maximum velocity of 159 +/- 48 cm/s (P < 0.01). False positive CADD diagnoses were due to tortuous graft vessels and a postbiopsy arteriovenous fistula. Sensitivity of CADD was 100%, specificity 86%. There were no DSA related complications. No impairment of graft function occurred. CADD allows renal angiography to be reserved to clarify an inconclusive ultrasound study and for definite diagnosis of angiomorphology and lesion classification. Intraarterial DSA of renal grafts in outpatients may be performed without an increased risk of procedure-related complications. PMID- 8462588 TI - Cell adhesion to streptavidin via RGD-dependent integrins. AB - Biotin-blocked streptavidin binds specifically (Kd approximately 3 x 10(-8) M) to cell surfaces, presumably via an RYD-containing sequence. This site is distinct from the biotin-binding cleft of the protein and bears high homology to the RGD containing cell-binding domain of fibronectin. We show here that various cell types adhere to immobilized streptavidin and that the soluble protein interferes specifically with cell adhesion to fibronectin substrata (with an IC50 of about 1 x 10(-7) M) but less so to other adhesive glycoproteins (e.g., collagen type I, vitronectin). Immunochemical evidence combined with peptide competition studies demonstrated that cells bind to streptavidin primarily via the major fibronectin receptor (the alpha 5 beta 1 integrin). The results suggest that streptavidin acts as a relatively strict fibronectin mimetic, thus reflecting the great similarity in their respective RYD/RGD sequence and the immediate flanking regions. The bacterial protein emulates and competes with fibronectin and other extracellular matrix adhesive proteins in the initial recognition and binding to cell surfaces, but appears not to induce subsequent processes (e.g., anchorage and spreading). Streptavidin may thus represent a novel example of bacterial protein mimicry of a key adhesion motif. PMID- 8462589 TI - The time courses of intracellular transport of some secretory proteins of rat liver are not affected by an induced acute phase response. AB - To study the effects of changed synthesis on intracellular transport of secretory proteins, an acute phase response was induced in rats. The synthesis and secretion of haptoglobin, complement C3, transferrin and albumin were then investigated by pulse labeling with [3H]leucine. Maximal increase in the syntheses of the positive acute phase proteins was observed after 24 h, amounting to an increase of nine, three and twofold for haptoglobin, C3 and transferrin, respectively. The synthesis of albumin decreased to a minimum after 48 h, reaching approximately one fourth of normal synthesis. The time courses for transit through rough endoplasmic reticulum and for secretion were determined after 36 h, and were found to be roughly unchanged for all four proteins despite the different changes in synthesis. The fraction of haptoglobin associated with the microsomal membrane was reduced during the acute phase response, but there was no significant change in membrane association as a function of time after labeling with [3H]leucine. It is concluded that the altered protein synthesis during an acute phase response in vivo has little effect on the time course of secretion of the proteins studied. Furthermore, the basal mechanisms for intracellular transport appear relatively unchanged during this condition. PMID- 8462590 TI - Retention of the fetoacinar pancreatic (FAP) protein to the endoplasmic reticulum of tumor cells. AB - The fetoacinar pancreatic (FAP) protein is a specific component of the human exocrine pancreas associated with the differentiation and proliferation of acinar cells. FAP expression is enhanced in cases of pancreatic exocrine cancer and it is found in relatively high concentrations in pathological pancreatic juices. However, tumor cell lines do not secrete FAP into the culture medium. In this paper we analyze the intracellular localization of FAP in cell lines and compare some biological properties of the tumoral FAP with the normal adult and fetal forms. Immunocytological experiments performed using Mab J28 which characterizes FAP, gave a staining pattern suggestive of FAP localization in the ER. Subcellular fractionation corroborated this localization and established that FAP is tightly associated with the microsomal membranes. The absence of reactivity of the tumoral FAP with wheat germ agglutinin lectin and its strong reactivity with concanavalin A is consistent with the idea that FAP in tumor cells does not reach the Golgi apparatus and it is consequently retained in the endoplasmic reticulum (ER). FAP contained in hepatic metastasis derived from pancreatic adenocarcinoma appeared to be similar, if not identical, to that expressed by cell lines. This supports the hypothesis that FAP retention in the ER of malignant cells is a physiological phenomenon and not the result of a modification of cell lines due to the culture conditions. FAP expressed by cancer cell lines and metastases appeared by sodium dodecyl sulfate polyacrylamide gel electrophoresis a homogeneous protein with a M(r) of 120,000. Instead, the secreted mature protein consists of a main component of M(r) 110,000 and shows pronounced polymorphism (dispersion from M(r) 110,000 to 80,000). Increased size of the ER-retained protein is likely due to elongation of the peptide chain. Defective processing in the ER as a result of amino acid mutation could therefore explain the behavior of this protein in tumors. PMID- 8462591 TI - Specific internalization of basal membrane domains containing the integrin alpha 6 beta 4 in dispase-detached cultured human keratinocytes. AB - The integrin alpha 6 beta 4 is polarized towards the basal side of basal keratinocytes and helps anchor these cells to the basement membrane components. We have found that cultured human epidermal keratinocytes, when detached from their culture substratum, as for grafting, using the enzyme dispase, rapidly internalize the basal membrane domains containing the integrin alpha 6 beta 4, while integrins of the very late antigen subtype remain on the cell surface. Detachment and incubation at 4 degrees C prevent this internalization, as well as the contraction of the detached sheet area. Subsequent incubation at 37 degrees C initializes this contraction and allows the basal integrin alpha 6 beta 4 to be internalized. We took advantage of this blockage to label upon detachment using immunogold techniques, the alpha 6 subunit present on the basal cell surface; then we studied its internalization with the electron microscope. This internalization pathway differs from classical receptor-mediated endocytosis, and intermediate filaments might possibly play a role in this process. Interestingly, 1 h after their internalization from the basal membrane, a third of the gold particles labeling the alpha 6 subunit was found between lateral membranes of basal cells, strongly suggesting that the integrin alpha 6 beta 4 can be partly recycled to the cell surface in these conditions. PMID- 8462592 TI - Receptor-mediated endocytosis of ricin in rat liver endothelial cells. An immunocytochemical study. AB - The endocytic pathway of ricin in sinusoidal liver endothelial cells (EC) was traced by means of immunocytochemical labeling of ultrathin cryosections. Ricin, a highly mannosylated glycoprotein, is internalized mainly by receptor-mediated endocytosis via the mannose receptor in the EC. Labeling of specimens fixed at different time points after injection of ligand showed that several subcellular compartments are involved in processing of endocytosed ricin. One minute after injection ricin is seen in coated pits, coated vesicles and cisternal-shaped endosomes. After 6 min, the ligand associates with electron-dense, spherical vesicles and electron-lucent vesicles, presumably representing late endosomes. In the same time period we observed labeling in the vicinity of the Golgi stack. At later time points, ricin is increasingly localized in lysosomes. Both late endosomes and lysosomes showed labeling for Igp120, the lysosomal membrane glycoprotein. To compare uptake of ricin with another mannosylated ligand, we coinjected ricin and mannosylated colloidal gold particles (Man-Aun). Man-Au20, injected 24 h before fixation as a marker for late endocytic compartments, was found in two distinct compartments, presumably representing late endosomes and lysosomes. The distribution of ricin and Man-Au10, the latter injected 15 min before fixation, in early endosomes was strikingly different, indicating that the structure of this compartment is important in the process of sorting of ligand and receptor. PMID- 8462593 TI - Isolation of cytolytic granules from sea urchin amoebocytes. AB - Calcium-dependent, heat-labile lytic activity was detected in whole Paracentrotus lividus coelomocytes. The molecules responsible for this activity were mainly expressed by an enriched amoebocyte population and were contained in cytoplasmic granules which could be isolated by Percoll density gradient centrifugation. The isolated cytoplasmic granules were small (0.1-0.25 micron) organelles containing the lysosomal marker arylsulfatase. The functional implication of our results is that P. lividus amoebocytes represent cytotoxic cells which mediate the killing event by a secretory phenomenon involving the release of cytolytic material from cytoplasmic granules. PMID- 8462594 TI - Sequential O-glycosylation of nuclear pore complex protein gp62 in vitro. AB - Gp62 is a nuclear pore complex glycoprotein of vertebrates containing multiple O linked N-acetylglucosamine monosaccharides. We have recently shown (Cordes et al., Eur. J. Cell Biol. 55, 31-47 (1991)) that gp62 of mouse and Xenopus laevis is predominantly glycosylated in the amino-terminal half of the molecule. Here we describe in vitro glycosylation in rabbit reticulocyte lysate of gp62 and of individual segments of this protein expressed as recombinant polypeptides in E. coli. Competition experiments between purified polypeptides revealed that gp62 exhibits in vitro at least two types of binding sites for a cytosolic N acetylglucosaminyltransferase resulting in a sequential glycosylation of the protein. High affinity binding sites for this glycosyltransferase were located in the amino-terminal domain between amino acids 248-341 of mouse gp62, whereas low affinity binding sites were scattered in the entire amino-terminal half. The segment containing amino acids 248-341 was able to compete with in vitro O glycosylation of gp62 subdomains containing low affinity binding sites. This gp62 segment was also able to compete with O-glycosylation of other unrelated cellular proteins in vitro. PMID- 8462595 TI - In situ localization of cAMP-dependent protein kinases in nuclear and chromosomal substructures: relation to transcriptional activity. AB - Catalytic (C) and regulatory subunits (RI, RII) of cAMP-dependent protein kinase (PKA) were localized in cell nuclei of various rat tissues by immunogold electron microscopy. A specific labeling within the interchromatin space was found to be associated with perichromatin fibrils, interchromatin granules, and coiled bodies. Condensed chromatin and perichromatin granules were not labeled. In the nucleolus, most gold particles were found in the dense fibrillar component. Quantitation of labeling densities for the C-subunit from cells at different stages of spermatogenesis indicated that the nuclear concentration of PKA varies inversely with the amount of condensed chromatin. No parallel alterations in C immunoreactivities were observed in the cytoplasm. Immunofluorescence studies on polytene chromosomes of Chironomus thummi with a confocal laser scanning microscope showed a significantly more intense labeling of the C-subunit in transcriptionally active sites (puffs) as compared to inactive bands. Our results indicate that local concentrations of PKA in the nucleus have physiological significance in the control of gene activity. In addition, they suggest that PKA plays a regulatory role also in RNA processing. PMID- 8462596 TI - Core substructure in phycobilisomes of red algae. II. The central part of the tricylindrical core--APCM--a constituent of hemidiscoidal phycobilisomes of Rhodella violacea. AB - The central part of the tricylindrical core of phycobilisomes from Rhodella violacea was isolated by hydroxylapatite adsorption chromatography followed by density gradient centrifugation. In the electron microscope negatively stained APCM complexes showed a tricylindrical face view with an edge length of 20 to 24 nm and a thickness of 9 to 10 nm in profile view. These complexes had a M(r) of 900,000, and a sedimentation coefficient 24S. The fluorescence emission maximum at room temperature lay at 671 nm when excited at 590 nm. The presence of the high molecular linker polypeptide LCM exclusively in APCM and the existence of beta AP19.5, alpha AP18, and beta AP17 were demonstrated in SDS-polyacrylamide gel electrophoresis. The presence of "trimeric" allophycocyanin complexes in a separate band, with a sedimentation coefficient 6S, confirms the uncoupling of these complexes from the core; their maximal fluorescence at 680 nm in the second derivative hints at alpha AP-8. The results indicate a high conformity in the molecular organization of the core of hemidiscoidal phycobilisomes of red algae (Rhodella violacea) and cyanobacteria (Mastigocladus laminosus). PMID- 8462597 TI - Depleting cell cholesterol alters calcium-induced assembly of tight junctions by monolayers of MDCK cells. AB - A role for lipids in the formation of tight junctions (TJ) has been proposed. Attempts to relate changes in whole cell phospholipid composition to the formation of TJs, however, have yielded equivocal results. The object in the present study was to relate changes in TJ of MDCK cells more specifically to alterations in plasma membrane lipids. Cholesterol, which resides primarily in the plasma membrane, was reduced by 25% after incubation of cell monolayers for 24 h in a low Ca2+ medium supplemented with (1-2 microM) Lovastatin, an inhibitor of hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase. This was associated with a halving of the time required for Ca2+ to induce TJ formation as monitored by transepithelial electrical resistance (TER). [3H]Mannitol flux, and morphometric measurements made on freeze fracture replicas confirm that the effects on TER reflect changes in the characteristics of the paracellular pathway. Peak and steady state values of TER were also elevated over control values. The changes in cholesterol content and the time course for TJ assembly were apparent at levels of Lovastatin which do not affect prenylation of proteins, and were prevented if 5 mM mevalonate was present along with Lovastatin. Paradoxically, despite a decrease of approximately 1/3 in the Ca concentration required to yield maximum rates of TJ assembly, 45Ca2+ uptake was actually reduced after cholesterol depletion. The data suggest that cholesterol may modulate the properties of membrane proteins and/or phospholipids which interact with Ca2+, possibly on the exoplasmic leaflet, during TJ assembly. PMID- 8462598 TI - von Willebrand factor storage requires intact prosequence cleavage site. AB - Large multimers of the adhesive glycoprotein von Willebrand factor (vWf) are stored in endothelial cells in rod-shaped granules called Weibel-Palade bodies, while small multimers are secreted constitutively. Expression of pro-vWf in other cells with a regulated pathway of secretion, results in formation of vWf containing storage granules that have a morphology similar to Weibel-Palade bodies. vWf expressed without its prosequence is not stored. To evaluate the importance of prosequence cleavage in vWf storage, the Arg at position -1, known to be necessary for cleavage, was mutated to Gly. Transfection of this cleavage mutant into two cell lines with a regulated pathway of secretion (RIN 5F and AtT 20 cells) led to the formation of large multimers. However, treatment of the cell lysates by the enzyme endoglycosidase H (Endo-H) did not reveal significant amounts of intracellular Endo-H-resistant vWf, which indicates the absence of a pool of stored processed vWf. In addition, no Weibel-Palade body-like structure was detected in these cells by immunofluorescence labeling with anti-vWf antiserum. Electron microscopy and immunocytochemistry of RIN 5F cells expressing the pro-vWf mutant confirmed the absence of Weibel-Palade body-like structures. In addition, anti-vWf-linked gold particles were found in the ER, occasionally in rounded granules and particularly in lysosomal structures which were abundant. We conclude that the formation of large aggregates is not sufficient to induce efficient vWf storage, and that the lack of cleavage of the prosequence may direct the mutant pro-vWf molecule to a degradative pathway. Therefore, the prosequence cleavage is a requirement for vWf storage. PMID- 8462599 TI - Isolation and characterization of mouse monoclonal antibodies against a human vascular endothelial cell-specific antigen. AB - A murine hybridoma clone was isolated secreting IgG-antibodies specific for human vascular endothelial cells. The antibody recognized a plasma membrane antigen (designated HECMA-112) of an apparent molecular weight of 112,000. Indirect immunofluorescence with cultured endothelial cells showed a staining pattern clearly distinct from previously described endothelial cell-specific antigens. The antibody bound to untreated as well as ethanol-fixed, confluent human umbilical vein endothelial cells (HUVEC) but not to other human primary cells (corneal endothelial cells, fibroblasts, keratocytes, lymphocytes, thrombocytes, or erythrocytes) or endothelial cells isolated from bovine or porcine aorta. HECMA-112 can be regarded as an additional marker for human vascular endothelial cells in vivo and in vitro. PMID- 8462600 TI - Preservation of differentiated phenotypes in cultured aortic endothelial cells by malotilate and phosphoascorbic acid. AB - Confluent bovine aortic endothelial cells (BAECs) formed a cobblestone-shaped cell monolayer when cultured on a collagen gel in a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's-F12 supplemented with 5% newborn calf serum. Within a few days, however, they lost cell-cell attachment and became fibroblastic. When BAECs were cultured in the same culture medium but further supplemented with either 10 micrograms/ml malotilate or 1 mM phosphoascorbic acid, the monolayer organization and the cobblestone-like cell morphology were maintained for more than 2 weeks although many sprout cells were observed underneath the monolayer. In contrast, if both malotilate and phosphoascorbic acid were present in the culture medium, a tight monolayer without underlying sprout cells was maintained for at least 4 months and the cells expressed factor VIII-related antigens and massively internalized acetylated low density lipoprotein. By electron microscopy, we observed well-developed gap and adherence junctions, Golgi apparatuses and vesicles many of which were open to the outside by fusing with either the apical or the basal surface, indicating high metabolic activity of the cells cultured for weeks in the same dish. Although malotilate treated BAEC monolayers secreted increased levels of prostacyclin (PGI2), the drug did not appear to directly affect the PGI2 production pathway since the similarly increased PGI2 production was noted in tight monolayers formed without the use of malotilate. Our results indicate that malotilate and phosphoascorbic acid together preserve differentiated phenotypes in cultured endothelial cells. PMID- 8462601 TI - Heterogeneity in the distribution of actin filaments in the endothelial cells of arteries and arterioles in the rat kidney. AB - The distribution of actin filaments (AFs) in arterial and arteriolar endothelial cells (ECs) was examined in situ by staining with rhodamine-phalloidin in the rat kidney after perfusion-fixation under physiological pressure. ECs possessed two populations of AF bundles, namely, peripheral bands (PBs) at the cell border and stress fibers (SFs) in the cytoplasm. The distribution of AFs was heterogeneous and exhibited three patterns in the arterial tree. In large arteries (> 120 microns in luminal diameter) ECs contained predominantly PBs in addition to occasional SFs mainly in the upstream side of cells (PB-pattern). In arteries with intermediate diameters (30-120 microns), both PBs and SFs were conspicuous (PB-SF-pattern). In small arteries and arterioles (< 45 microns), SFs were prominent and PBs were rare (SF-pattern). In electron micrographs, we found that PBs were attached not to the lateral but to the basal plasma membrane via electron-dense materials and that SFs included two subpopulations, namely, thick basal and thin apical SFs. Morphometric analysis revealed that the length density of PBs was higher in segments with the PB-pattern than in those with the PB-SF pattern. The length density of SFs was significantly higher in the SF-pattern than in the PB-SF-pattern, whereas there was little difference in this parameter among vessel segments with the SF-pattern. We suggest that PBs and SFs are fundamentally structures that anchor ECs on the substratum, and are differentiated according to their different mechanical burdens. PMID- 8462602 TI - Multiple plasma membrane-associated MTOC systems in the acentrosomal cone cells of Drosophila ommatidia. AB - Multiple plasma membrane-associated microtubule-organizing centers operate in the cone cells of Drosophila ommatidia. A transcellular array of about 250 microtubules assembles in each cone cell during late pupal ommatidial morphogenesis. While these arrays are assembling, cone cells do not possess conventional centriole-containing centrosomal microtubule-organizing centers. The microtubules are associated with plasma membrane-associated plaques at both the apical and basal surfaces. During assembly of the arrays there is a progressive decrease in the number of microtubules/cell cross section at successively lower levels in each cell which is indicative of apicobasal microtubule elongation. In this respect, assembly of the arrays closely resembles that of transcellular 15 protofilament microtubules in late pupal wing cells (Mogensen et al. J. Cell Biol. 108, 1445-1452 (1989)). However, cone cell microtubules are almost certainly of the 13 protofilament variety as found in eukaryotic cells generally. We suggest that plasma membrane-associated microtubule-organizing centers are widely employed in polarized epithelia in Drosophila during late pupal morphogenesis. PMID- 8462603 TI - Characteristic and differential calcium signals from cell structures of the root cap detected by energy-filtering electron microscopy (EELS/ESI). AB - Characteristic calcium signals were analyzed in structures of three cell types of the root cap of cress: statocytes, meristematic cells and secretion cells. Twenty four hour-old roots were fixed with glutaraldehyde (postfixed with osmiate/potassium bichromate) or with potassium permanganate. No visible precipitates were formed, but calcium signals typical for different cell structures could be detected by means of energy-filtering transmission electron microscopy (EELS/ESI). In statocytes, calcium signals were recorded from the plasma membrane, the membranes of the endoplasmic reticulum, the amyloplast envelope and the mitochondrial membranes. In contrast to the excitable statocytes, the two other, non-excitable cell types, meristematic and secretion cells, exhibited much lower intensities of the calcium signals recorded from the same membrane systems. The revealed characteristic calcium-related properties of the different membrane systems may be related to the special function of statocytes, namely transduction of the gravity stimulus. In all three cell types, additional calcium signals were recorded from cell structures with well known calcium contents, i.e., mitochondrial granules, starch grains and cell walls. For the first time, clear calcium signals were detected from the lipid bodies which are mobilized during the developmental stage of the examined roots. It is supposed that free fatty acids and lipases are the binding sites for calcium. The reliability of the applied method is especially proven by comparison of the electron microscopic images from lipid bodies according to the two different fixation methods. After glutaraldehyde fixation followed by osmiate/potassium bichromate postfixation, the lipid bodies were well fixed and appeared homogeneously grey with homogeneous calcium signals. However, due to potassium permanganate fixation the lipid bodies were only partly fixed; they had an electron-lucid core, from which the lipids are lost during the dehydration procedure, without calcium signals and an electron-dense border zone, which is a reaction product of potassium permanganate with triacylglycerols, with calcium signals. PMID- 8462604 TI - Criteria for labelled meals for gastric emptying studies in nuclear medicine. PMID- 8462605 TI - Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations. AB - Seventy female patients who had been treated with high doses of iodine-131 for differentiated thyroid cancer (DTC) and who had a subsequent pregnancy were evaluated. The total 131I dose ranged from 1.85 to 16.55 GBq (mean +/- SD = 4.39 +/- 25.20 GBq). Age at first therapy ranged from 15 to 36 years (mean +/- SD = 24.3 +/- 5.0 years) and the interval from 131I therapy to pregnancy varied from 2 to 10 years (mean +/- SD = 5.3 +/- 2.8 years). The estimated radiation dose to the gonads ranged from 10 to 63 cGy (mean +/- SD = 24.0 +/- 13.5 cGy). All patients were treated with L-thyroxine at doses capable of suppressing thyroid stimulating hormone. Seventy-three children were followed-up and seven pregnancies are still in progress. One child was affected by Fallot's trilogy and three had a low birth weight through with subsequent normal growth; the others were healthy with subsequent normal growth. No newborn with clinical or biochemical thyroid dysfunctions was found. Two spontaneous abortions during the second month of pregnancy were recorded. One of two patients in question subsequently had two healthy children. On the basis of these data, previous administration of high 131I doses does not appear to be a valid reason for dissuading young female DTC patients from considering pregnancy. However, patients should be advised to avoid pregnancy after 131I administration for a period sufficient to ensure complete elimination of the radionuclide and to permit confirmation of complete disease remission, i.e. at least 1 year in our opinion. PMID- 8462606 TI - Comparison of simultaneous 99mTc-HMPAO and 111In oxine labelled white cell scans in the assessment of inflammatory bowel disease. AB - Forty-seven patients, 29 with chronic inflammatory bowel disease (IBD) and 18 with presumed irritable bowel syndrome, including one with uncomplicated diverticular disease, were studied with simultaneous technetium-99m hexamethylpropylene amine oxime and indium-111 oxine labelled leucocyte scans performed at 1, 3 and 24 h. Twenty-seven patients with IBD had active disease as judged by clinical and laboratory criteria and all of these had positive scans with both agents. No false positive studies were obtained. The 1-h 99mTc-HMPAO WBC scans showed the same distribution to disease as the 3-h 111-In WBC scans, with no difference in intensity (P < 0.92); they showed more extensive disease (P < 0.02) and more intense uptake (P < 0.001) than did the 1-h 111-In scans. The 3 h 99mTc-HMPAO WBC scans showed more extensive disease (P < 0.002), with greater intensity (P < 0.0005), than did the 3-h 111In WBC scans. Physiological bowel activity on 3-h 99mTc-HMPAO WBC scans was present in 12 patients but was faint and did not interfere with assessment of disease extent and activity. It is concluded that in terms of isotope availability, radiation dosimetry and image quality, 99mTc-HMPAO is the agent of choice in detecting active IBD, with localization of disease possible at 1-h after re-injection and optimal resolution and definition of disease extent at 3 h. A negative scan reliably excludes active disease. PMID- 8462607 TI - Evaluation of white cell scintigraphy using indium-111 and technetium-99m labelled leucocytes. AB - Indium-111 oxine labelled leucocyte (111In oxine leucocyte) scintigraphy is the test of choice in detecting occult infection and localising focal inflammation. 111In oxine labelling is technically difficult and expensive and leucocyte labelling with technetium-99m stannous colloid (99mTc Sn colloid) has been considered to be an alternative. Leucocytes from 40 cases referred for investigation of occult infection or localisation of inflammation were simultaneously labelled with 111In oxine and 99mTc Sn colloid with dual isotope acquisition performed at 1, 3 and 24 h. Twenty-four hour 99mTc Sn colloid scans were corrected for 111In downscatter. Each case was independently interpreted by two experienced observers. Twenty-one patients demonstrated positive 111In oxine leucocyte scans. Using 111In oxine leucocyte scans as the gold standard, 99mTc Sn colloid leucocyte scanning had an overall sensitivity of 86% and a specificity of 95%. Clinical follow-up verified that three patients had false negative 99mTc Sn colloid leucocyte scans and one patient had a false positive. Further clinical evaluation of 99mTc Sn colloid labelled leucocytes is required before they can become a reliable replacement for 111In oxine leucocytes. PMID- 8462608 TI - Sympathetic innervation of the left ventricle is impaired in arrhythmogenic right ventricular disease. AB - Arrhythmogenic right ventricular disease (ARVD) is a disease of unknown origin that primarily affects the right ventricle and is characterized by ventricular tachyarrhythmias which may lead to syncope and even, though rarely, sudden cardiac death. In 25 patients with ARVD, sympathetic innervation of the left ventricle was assessed by iodine-123 metaiodobenzylguanidine single photon emission tomography (123I-MIBG SPET). In addition, thallium-201 SPET was performed. The diagnosis of ARVD was made by an electrophysiological study and right and left heart catheterization including right ventricular endomyocardial biopsy. Ischaemic heart disease was excluded by coronary angiography. A group of seven patients without any evidence of heart disease served as a control group. Twenty-two of the 25 patients showed reduced uptake of 123I-MIBG. The abnormal areas were located predominantly in posterior and posteroseptal segments of the heart. No focus of increased 123I-MIBG activity could be demonstrated. No patient had signs of left ventricular involvement on left ventricular angiography. In contrast to the results of the 123I-MIBG SPET, those of 201T1 SPET were normal in 16 patients. The remaining nine patients showed areas of slight hypoperfusion not correlated with the reduced 123I-MIBG uptake. 123I-MIBG scintigraphy allows detection of left ventricular adrenergic dysinnervation in ARVD patients without morphological or functional abnormalities of the left ventricle. PMID- 8462609 TI - Prospective evaluation of thallium-201 reinjection in single-vessel coronary patients undergoing coronary bypass surgery. AB - Twenty-two patients with single-vessel left anterior descending coronary artery disease were investigated by means of dipyridamole stress thallium-201 myocardial perfusion scintigraphy, using single photon emission tomography (SPET), 1 week before and 2-5 weeks after coronary bypass surgery. The dose of dipyridamole was 0.56 mg/kg, and the injected activity of 201Tl was 74 MBq. Before surgery, and after completion of the redistribution study, a further 37 MBq of 201Tl was injected. Ten minutes and 1 h later, repeated SPET imaging were performed. SPET images were evaluated both subjectively and semiquantitatively, using a five grade segmental defect score system, with higher scores for more severe perfusion defects. Before surgery, the 3-h redistribution images revealed complete or partial persistence of the perfusion defects in all patients. On the images taken 10 min after reinjection, these defects were completely filled in four cases, and partially filled in ten cases. Further positive changes were observed on the 1-h post-reinjection images in four cases. Three of the 1-h post-reinjection images exhibited a paradox redistribution. The stress images after surgery corresponded well to the 201Tl distribution on the preoperative 1-h post-reinjection images in 11 cases. The average of the segmental defect severity scores was 17.0 after stress, 10.1 at rest, 7.1 10 min after reinjection and 6.4 1 h after reinjection. After surgery, the average of both the post-stress and the 3-h redistribution scores was 3.1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462610 TI - Myocardial scintigraphy with thallium-201 and technetium-99m-hexakis methoxyisobutylisonitrile in left bundle branch block: a study in patients with and without coronary artery disease. AB - In left bundle branch block (LBBB) thallium-201 myocardial scintigraphy frequently reveals septal abnormalities in the absence of coronary artery disease (CAD) and gives rise to "false-positive" results in patients with suspected CAD. It has not yet been clarified which pathophysiological mechanism is responsible for these perfusion abnormalities. A total of 66 patients with constant LBBB were investigated with 201Tl or technetium-99m-hexakis-methoxyisobutylisonitrile (MIBI), 62 underwent coronary angiography. Of 12 patients without left anterior descending artery (LAD) or right coronary artery (RCA) stenoses, 11 had a reversible septal activity deficit after 201Tl stress injection, whereas 20 of 22 patients without relevant CAD showed a constant stress/rest septal deficit using MIBI. Regarding patients with significant LAD and/or RCA stenoses, both radio pharmaceuticals almost always showed a "reversible" septal deficit: with 201Tl in 15 of 16 individuals and with MIBI in 14 of 15. In 12 patients 201Tl was reinjected at rest. In those who had LAD or RCA stenoses (n = 5), early septal activity uptake after stress injection was poorer than that after rest injection; in the absence of CAD (n = 7), septal stress uptake corresponded with that of rest injection. It is concluded that septal perfusion abnormalities in LBBB and the absence of CAD are characterized by an exercise-independent reduction of septal blood flow per mass of viable myocardium and that stress/rest injection protocols of myocardial perfusion tracers are able to differentiate between LBBB with and without CAD. PMID- 8462611 TI - Beta-oxidation of 1-[14C]-17-[131I]-iodo-heptadecanoic acid following intracoronary injection in humans results in similar release of both tracers. AB - Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [123I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, 14CO2 and inorganic 131I appeared nearly in parallel, with a peak time of 4-5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (123I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through beta-oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [11C]palmitic acid and [123I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals. PMID- 8462612 TI - Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion. AB - To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (Kmono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112 +/- 0.020 min-1 vs 0.065 +/- 0.015 min-1 at rest) (P < 0.001) in proportion to the increase in the pressure-rate product. Kmono in the right ventricular (RV) myocardium also increased (0.080 +/- 0.018 min-1 vs 0.034 +/- 0.013 min-1 at rest) (P < 0.001), with an excellent correlation with the LV Kmono (r = 0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158% +/- 81%) than that in LV Kmono (79% +/- 39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects. PMID- 8462613 TI - N-(2-diethylaminoethyl)-4-[123I]iodobenzamide as a tracer for the detection of malignant melanoma: simple synthesis, improved labelling technique and first clinical results. AB - In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4 [123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4-[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far. PMID- 8462614 TI - Determination of the technetium-99m mercaptoacetyltriglycine plasma clearance in children by means of a single blood sample: a multicentre study. The Paediatric Task Group of the EANM. AB - A multicentre European study was undertaken in order to determine a reasonable algorithm allowing the determination of overall technetium-99m mercaptoacetyltriglycine clearance using a single blood sample. Employing multiple blood sample clearance as a reference method, it was shown that an acceptable estimation of the MAG3 renal clearance could be obtained using a blood sample taken at any time between 30 and 40 min after tracer injection. After correction for body surface area, comparison of clearance determined using (a) the single blood sample and (b) the multiple blood samples provided a coefficient of correlation of 0.949 and an SEE of 27 ml/min. This algorithm is valid for clearance values higher than 100 ml/min/1.73 m2 and for children older than 1 year of age. PMID- 8462615 TI - Verification of the integral transformation of the projections technique for scatter correction in positron tomographs. AB - A scatter correction algorithm, based on the integral transformation of the projections, has been implemented when using the C.N.R. positron tomograph in Pisa. The performance of the method has been evaluated by measurements on ad hoc phantoms. The technique allows a significant average reduction of the reconstructed scatter fraction. The limitations of this approach have also been investigated. PMID- 8462616 TI - A simple scintigraphic method for continuous monitoring of gastric emptying. AB - A new and simple scintigraphic method for the measurement of gastric emptying was developed and validated. The test meal consists of 200 g potato mash mixed with 0.5 g Dowex 2X8 particles (mesh 20-50) labelled with 37 MBq (1 mCi) technetium 99m. After ingestion of the meal, sequential dynamic 15-s anteroposterior exposures in the supine position are obtained for 90 min. A second recording sequence of 20 min is added after a 30-min interval. The results can be displayed as immediate cine-replay, as time-activity diagrams and/or as activity retention values. Complicated mathematical fittings are not necessary. The method lends itself equally to the testing of in- and outpatients. PMID- 8462617 TI - Highlights of the annual meeting of The European Association of Nuclear Medicine, Lisbon 1992. How to increase the impact of nuclear medicine on clinical decision making. PMID- 8462618 TI - The use of SEP-PAK SI cartridges for the preparation of gallium chloride from the citrate solution. PMID- 8462619 TI - Lack of relationship between hip and spine bone mineral density and oral contraceptive use. AB - The aim of this study was to examine the relationships between oral contraceptive use and bone mineral density at the hip and spine. Community based women aged 41 76 years (n = 841) were recruited from four general practices in Cambridge. Each subject completed a health questionnaire. Spine (L2-L4, n = 841) and hip (n = 833) bone mineral density were measured by dual energy X-ray absorptiometry using the Hologic QDR-1000. After adjustment for age, there was no significant difference in regional bone mineral density between ever and never users of oral contraceptives. Similar results were obtained after stratifying for potential confounding factors including menopausal status, parity, smoking, hormone replacement therapy use, and body mass index. There was no relationship between duration of oral contraceptive use and bone mineral density. These results suggest that there is no relationship between oral contraceptive use and bone mineral density at the hip and spine in middle-aged women. PMID- 8462620 TI - Very long chain n-3 and n-6 polyunsaturated fatty acids inhibit proliferation of human T-lymphocytes in vitro. AB - The effect of marine n-3 polyunsaturated fatty acids on proliferation of human T cells in vitro was compared to other polyunsaturated, monounsaturated and saturated fatty acids. Monoenes and saturated fatty acids had little effect on T cell proliferation. Eicosapentaenoic acid and docosahexaenoic acid exerted a strong dose-dependent inhibitory effect on proliferation of mitogen- or antigen stimulated T-cells, similar to that observed for arachidonic acid. Sixty microM of albumin-bound eicosapentaenoic acid or arachidonic acid promoted 25-40% inhibition of proliferation of T-cells stimulated with mitogen, whereas the same concentration of albumin-bound docosahexaenoic acid promoted 60% inhibition. When epidermal cells (Langerhans cells) were used as antigen-presenting cells, 100 microM of albumin-bound eicosapentaenoic acid or arachidonic acid caused 40% inhibition on T-cell proliferation. Low density lipoprotein (LDL), isolated after four months of dietary intake of fish oil or corn oil, inhibited mitogen stimulated T-cell proliferation in a dose-dependent manner. Fish oil- and corn oil-enriched LDL showed similar ability to inhibit T-cell proliferation. Epidermal cells preincubated with docosahexaenoic acid, and extensively washed before adding purified T-cells and antigen, resulted in a strong inhibition of T cell proliferation, whereas preincubation of purified T-cells with docosahexaenoic acid did not cause any inhibitory effect. Cyclooxygenase and lipoxygenase inhibitors (indomethacin, acetylsalicylic acid, nordihydroguaertic acid) did not affect the antiproliferative effect of eicosapentaenoic acid and arachidonic acid, neither did the antioxidants butylated hydroxytoluene or alpha tocopherol. Eicosanoids, (PGE2, PGE3, LTB4, LTB5 and lipoxin A or lipoxin B) added directly to mitogen-stimulated peripheral blood mononuclear cells (PBMC) did not influence T-cell proliferation significantly. Decreased viability was observed when mitogen-stimulated lymphocytes were cultured with essential polyunsaturated fatty acids, whereas the viability of unstimulated lymphocytes was hardly influenced by the same fatty acids. We conclude that; (a) pharmacological albumin-bound concentrations of the highly unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid promote a strong antiproliferative effect on mitogen- and antigen-stimulated human T-cells: (b) docosahexaenoic acid can suppress accessory cell function and consequently suppress T-cell activation; (c) physiologic concentration of LDL particles rich in n-3 and n-6 fatty acids, both promote a dose-dependent antiproliferative effect on mitogen-stimulated PBMC; (d) the inhibition is independent of eicosanoid metabolites; and (e) lipid peroxidation seems unlikely to be responsible for the antiproliferative effect. PMID- 8462621 TI - Reverse cholesterol transport: relationship between free cholesterol uptake and HDL3 in normolipidaemic and hyperlipidaemic subjects. AB - High density lipoproteins (HDL) are responsible for the Reverse Cholesterol Transport (RCT). The role of the composition of the HDL particle in RCT, involving free cholesterol (chol) uptake from cell membranes, is not completely understood. We have therefore studied the uptake capacity from subjects with a wide variety of plasma HDL cholesterol concentrations in an HDL-receptor free model consisting of bovine heart mitochondrial membranes labeled with [14C]cholesterol. HDL were isolated by molecular sieve chromatography from fresh plasma samples of eight subjects with low plasma HDL chol concentrations (< or equal to 1.0 mmol L-1) and 15 subjects with normal HDL chol concentrations. The latter were subdivided into an intermediate (HDL chol: 1.0-1.4 mmol L-1; n =9) and a high HDL chol group (> or equal to 1.4 mmol L-1; n = 6). In the HDL fractions isolated by chromatography (cHDL), total chol and apolipoprotein (apo) AI were measured. Free chol uptake was significantly decreased by 32% in the tertile with the lowest plasma HDL chol (49.1 +/- 15.8 arbitrary units; mean +/- SD), compared to the tertile with high HDL chol (72.1 +/- 16.6 au). Linear regression analysis showed a positive correlation between the free chol uptake and plasma HDL3 concentrations (r = 0.61; P < 0.01), HDL chol (r = 0.56; P < 0.01), HDL associated apo AI (R = 0.46; P < 0.05), cHDL apo AI (r = 0.56; P < 0.05) and cHDL chol (r = 0.46; P < 0.05) in all subjects combined. Stepwise multiple-regression analysis confirmed the association of [14C] cholesterol uptake with plasma HDL3 concentrations (beta, 0.61; P = 0.004). No correlations were found between free chol uptake and total plasma apo AI (r = 0.26. ns) or HDL2 (r = 0.27; ns). After an oral fat load in four FCH patients, free chol uptake paralleled the changes in plasma HDL 3 chol concentrations. We conclude that HDL3 is involved in the early steps of RCT and low HDL 3 levels may result in less efficient RCT in hypertriglyceridemia. PMID- 8462622 TI - Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria. AB - We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis. The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mitochondrial electron energy-loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients. These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this failure is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP patient. PMID- 8462623 TI - Non-insulin dependent diabetes mellitus: defects in insulin secretion. AB - NIDDM is a heterogeneous disorder, characterized by defects in insulin secretion as well as in insulin action. Several pathophysiological mechanisms are involved in the development of disturbances in insulin secretion. One of the histological features of islets of NIDDM patients is the deposition of amyloid-like material. Accumulation of amyloid over many years can lead to slowly progressive disruption of islet architecture and possibly to some of the abnormalities in insulin secretion, as found in NIDDM patients. Loss of pulsatility is the earliest detectable abnormality of insulin secretion in the disease, either as a specific early defect or as a disturbance caused by minimally elevated blood glucose levels. Although it has been shown that maximum insulin release is decreased by 50% in NIDDM, the B-cell sensitivity to glucose appears to be normal. Coregulatory factors such as prostaglandins do not play a major role in the derangements of insulin secretion in NIDDM. An imbalance between stimulatory and inhibitory endorphins, or in sympathetic tone may be of more importance. Hyperglycaemia by itself has a deleterious effect on insulin release, and may perpetuate the disturbances of insulin secretion. PMID- 8462624 TI - Vasoactive peptides in Bartter's syndrome. AB - Patients with Bartter's syndrome exhibit an increased vascular resistance to the pressor effects of angiotensin II and noradrenaline. Further, an increased production of vasodilating renal prostaglandins, perhaps mediating the vascular unresponsiveness, has been hypothesized in this syndrome based on high urinary prostaglandins. To determine whether different peptides might contribute to blood pressure control in this syndrome, the basal immunoreactive plasma levels of an array of vasoactive peptides and catecholamines were analysed in six patients with Bartter's syndrome. Among the vasoconstrictors analyzed, the mean plasma levels of noradrenaline (NA), adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) were significantly increased as compared to healthy subjects (P = 0.030, 0.046 and 0.001, respectively). The plasma level of the vasodilator substance P (SP-LI) was also higher in these patients (P = 0.057). These results indicate that in Bartter's syndrome the vasoconstrictive effect of catecholamines and angiotensin II may be enhanced by concomitant NPY release. Whether a release of the vasodilator substance P is an independent mechanism or represents a reflex response to the increased secretion of angiotensin II, catecholamines and/or NPY remains to be established. However, the significance of these biochemical findings for blood pressure maintenance in Bartter's syndrome remains to be settled. PMID- 8462625 TI - Diabetes mellitus induces accelerated growth of aortic smooth muscle cells: association with overexpression of PDGF beta-receptors. AB - The mechanism of diabetic macroangiopathy was studied from the view point of phenotypic change of aortic smooth muscle cells (SMC). The growth rates of cultured SMC of diabetic rats or rabbits were higher than those of non-diabetic animals (controls). This difference of the growth responses was observed specifically with platelet-derived growth factor (PDGF). Of the three PDGF dimers, PDGF-AB heterodimer (PDGF-AB) and PDGF-BB homodimer (PDGF-BB) stimulated growth of diabetic SMC more than that of control SMC but PDGF-AA homodimer (PDGF AA) did not. The binding of 125I-PDGF to the diabetic SMC was greater than that to control SMC. This was due to increase in the number of cell surface receptors for PDGF. On in vitro culture, SMC from diabetic rats expressed more PDGF beta receptor mRNA than SMC from non-diabetic rats. Moreover, in vivo, the aortic media of diabetic rabbits expressed PDGF beta-receptor mRNA, but that from non diabetic rabbits did not. Thus diabetic SMC over-react on PDGF stimulation through over-expression of the PDGF beta-receptor gene. The significance of this fact in development of diabetic macroangiopathy is discussed. PMID- 8462626 TI - Fc-gamma receptor III shedding by polymorphonuclear cells in primary Sjogren's syndrome. AB - A sandwich enzyme-linked immunosorbent assay was developed to assess Fc-gamma receptor III (Fc gamma RIII), based on a combination of two non-competing monoclonal antibodies. This receptor was detectable in the serum of eight out of 23 patients with primary Sjogren's syndrome and two out of 23 normal controls. The proportion of Fc gamma RIII-carrying polymorphonuclear (PMN) cells was lower (P < 0.05) in the patients with cell-free Fc gamma RIII (90.4 +/- 7.5%) than in the remainder (84.8 +/- 8.3%). The PMN cell functions were evaluated and the diminished adherence (71.7, geometric mean) and chemotaxis (1.23) paralleled the Fc gamma RIII release. The relative inefficiency of PMN cells in SS might be due to phagocytosis of immune complexes. PMID- 8462627 TI - Studies on coprophagy in experimental animals. PMID- 8462628 TI - [Diurnal rhythms in locomotor activity of the house musk shrew, Suncus murinus]. AB - A diurnal rhythm of locomotor activity in male and female house musk shrews (Jic:SUN) aged approximately one year was observed under a schedule of 12 hr light and 12 hr darkness (light on at 07:00) over a period of 10 days. In general, the pattern of locomotor activity was similar in both sexes, with around 24-hr diurnal rhythm. A few typical patterns of locomotor activity in these animals were as follows: A. Locomotion interval was close in the light phase, while was sparse in the dark phase. B. As opposed to the pattern of A, locomotion interval was close in the dark and sparse in the light phases. C. Its interval remains stationary through a whole day. PMID- 8462629 TI - Hereditary hydronephrosis in C57L/MsNrs mice. AB - Inbred C57L/MsNrs mice (66 males and 72 females) maintained at the National Institute of Health, Japan, were examined grossly for hydronephrosis. Unlike the hydronephrotic strains of mice reported so far, C57L mice showed no sex-related difference in the incidence (62% in males and 75% in females; P > 0.05) and severity of hydronephrosis. The right kidney was more severely affected than the left kidney in both sexes. Age appeared to have no influence on the incidence. PMID- 8462630 TI - Morphological studies on the bone and cartilage of laboratory animals. PMID- 8462631 TI - Effects of p-chloroamphetamine (PCA) on ejaculation in aged rats. AB - In general, sexual activity in normal animals declines with increasing age. In aged male rats, for example, no ejaculation occurs when paired with receptive females. The ejaculatory response induced by p-chloroamphetamine (PCA) in aged adult rats, 14 to 18 months of age, was observed. The animals were treated intraperitoneally with PCA. The ejaculation rates were 0.28.6, 57.1 and 100% at doses of 0.3125, 0.625, 1.25 and 2.5 mg/kg, respectively. These animals, with a few exceptions, showed an ejaculation within 2 hrs of PCA injection. These data for aged adults are similar to those for young adults. PMID- 8462632 TI - A new method for the long-term collection of the bile from the unrestrained rabbit. AB - A method for the long term bile collection of the unrestrained rabbit was developed. A steel needle was tunneled subcutaneously from the dorsum of the neck to the abdomen of the animal. A catheter was threaded through this needle from the dorsum and brought out below the abdomen. The catheter was introduced into the common bile duct and the tip on the dorsum was passed through a steel protective coil which was attached to the dorsal skin. This method allows the animal to move freely in the metabolic cage. The bile of the unrestrained rabbit weighing 3.7 kg was collected for 120 hr at 8.9-10.2 ml per hour of the output rate. PMID- 8462633 TI - Isolation of Salmonella from impounded dogs introduced to a laboratory. AB - Isolation of Salmonella from the feces of impounded dogs was carried out to make clear the recent microbiological condition of dogs introduced into our facilities. Salmonella was isolated from 10 out of 283 samples (3.5%). Inparticular, during the first week after introduction, Salmonella was isolated from nine out of 74 dogs (12.2%). The isolation rate during the first week after introduction was significantly higher than that for dogs introduced later. No isolates were detected from dogs reared for more than 3 weeks after introduction. This study indicates that impounded dogs had the highest risk of infecting a person with Salmonella during the first week after introduction into our laboratory animal facilities, and that we need to pay attention to this fact when handling them. PMID- 8462634 TI - [Immunohistochemical and morphometric studies on the development of the thyroid, parathyroid and ultimobranchial body in Xenopus laevis Daudin]. AB - The development of the thyroid, parathyroid and ultimobranchial body was examined by immunohistochemistry and morphometric analysis in the larvae of Xenopus laevis Daudin from the time immediately after hatch to the end of metamorphosis. The thyroid appeared at stage 43 and began to secrete thyroglobulin from stage 47/48. Both the volume of the thyroid and the height of the follicular epithelium reached the peak at stage 61 and decreased thereafter towards the end of metamorphosis at stage 66. The parathyroid first appeared at stage 43 as the thickening of the wall of the third and fourth visceral pouch. The volume of the parathyroid gradually increased with the progress of development until the end of metamorphosis. The ultimobranchial body appeared at stage 45 as a recess of the epithelium lining the floor of the pharynx. It became follicular in the structure at stage 53. Its volume reached the peak at stage 61 and decreased thereafter towards the end of metamorphosis. Calcitonin-immunoreactive cells first appeared in the ultimobranchial body at stage 47/48, showed the most intense reaction at stage 59, and rapidly decreased in number thereafter towards the end of metamorphosis. PMID- 8462635 TI - [Diurnal fluctuations of heart rate and locomotive activity in the vole (Microtus arvalis)]. AB - Diurnal fluctuations of heart rate and locomotive activity were observed in the unanesthetized and unrestrained voles (Microtus arvalis) and mice, and the differences in these biological characters between voles and mice were also investigated. The mean heart rate of vole in whole day was lower than that of mice. In voles, there were no significant differences in the mean heart rate between in light period and in dark period. It was observed that most of voles were active in not only dark period but light period. On the other hand, in mice, the mean heart rate in dark period was significantly higher than that in light period, and the nocturnal habit was shown obviously in the locomotive activity. In voles, the ultradian rhythmicities of 95-210 min in the heart rate and those of 160-210 min in the locomotive activity were recognized, and the fluctuations of heart rate due to ultradian rhythmicity in voles exceeded the difference between the heart rate in light period and that in dark period. In mice, one of three animals showed the ultradian rhythmicity of 85 min in the fluctuation of heart rate. Diurnal fluctuation of the heart rate in voles consisted of the two patterns which the peaks of heart rate were coincident with the active period or the resting period. However, all the peaks of heart rate in mice were coincident with the active period. These results suggested that the fluctuations of heart rate in voles were dependent on ultradian rhythmicities in addition to the circadian rhythmicities. PMID- 8462636 TI - Morphometric profiles of the mandible of SMXA recombinant inbred strains of mice and strain identification on the basis of mandible measurements. AB - SMXA recombinant inbred (RI) strains were derived from the F2 generation of a cross between two progenitor inbred strains, A/J and SM/J, which differ considerably with respect to many characters. In order to determine the morphometric profiles of the mandible of SMXA RI strains and to identify these strains, principal component and discriminant analyses (mandible analysis) were carried out using 11 mandible measurements. Principal component analysis revealed that the mandibles of each strain have their own characteristic size and shape. The RI strains, however, were roughly divided into 15 groups based on the morphometric profile of their mandibles. Discriminant analysis showed the probability of erroneous discrimination to be 6.49% (20/308) for the males and 8.06% (27/335) for the females. In both sexes, most of the erroneous discrimination (13 in the male, 17 in the female) occurred between RI strains having comparatively similar morphometric profiles. This suggested that all of the SMXA RI strains examined could be regarded as genetically homogeneous within each strain. PMID- 8462637 TI - Lung free cells following short-term inhalation of coal fly ash particles in golden hamsters. AB - Male golden hamsters were exposed to coal fly ash (FA) at the concentration of 2 or 5 mg/m3 for 10 days (20 hr/day, Experiment 1) or 5 mg/m3 for 4 weeks (10 hr/day, 7 days/week) and maintained in clean air condition for subsequent 4 weeks (Experiment 2) to investigate the effect on the induced changes of lung free cells. Free cells were collected by lung lavage in Exp. 1 and histologically examined in lung sections in Exp.2. In Exp. 1 the number of alveolar macrophages (AMs) increased in a dose-dependent manner. In Exp. 2 AMs increased till at 2 weeks of exposure, while the subsequent increase did not occur. The ratio of particle-laden AMs increased in a dose- and time-dependent manner in each exposed group. Particle number ingested in AMs tended to increase with exposure time. In the recovery period in Exp. 2 the ratio of particle-laden AMs reduced from about 80 to 20% at the 1st week after the cessation of exposure and remained at the similar level to the termination of the experiment. On the other hand decrease in the number of total AMs was slight in the recovery period. These results suggest that the pool size of AMs is mainly dependent on the inhaled dust concentrations and some of particle-laden AMs remain in alveoli for a long time. The number of polymorphonuclear leukocytes (PMNs) also increased after inhalation of FA particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462638 TI - [Antibody responses against Japanese cedar pollen allergen (Cry j I) in different strains of rats]. AB - We established an IgE-capture ELISA for rat IgE antibody, and examined rat strain differences in the antibody responses against the major allergen of Japanese cedar pollen (Cry j I). First, IgE-capture ELISA and passive cutaneous anaphylaxis (PCA) method were compared. IgE-capture ELISA was found to be, in sensitivity, about 10 times higher than, and, in specificity, equal to, PCA. Second, seven strains of rat were immunized three times at days 0, 14 and 28 by intraperitoneal injections of 1 or 10 micrograms Cry j I mixed with 4 mg aluminium hydroxide gel. Anti-Cry j I IgE was detected by IgE-capture ELISA. Anti Cry j I IgG and IgM responses were found not significantly different among different strains, but IgE responses in Brown-Norway (BN) rat were about 10 times higher than in other strains of rats. These results suggest that BN rat may be a useful animal model for studying physiological and pathological changes in the nose after pollen challenge to that organ. PMID- 8462639 TI - [Effects of repeated restraint stress at 30-minute intervals during 24-hour on serum testosterone, LH and glucocorticoids levels in male Japanese monkeys (Macaca fuscata)]. AB - We investigated effects of frequent blood collections under the compulsory restraints on serum testosterone, LH and glucocorticoids in adult male Japanese monkeys. Blood samples were withdrawn from three animals at 30-min intervals and two animals at 4-hr intervals during 24 hr. Serum testosterone and LH were measured by a radioimmunoassay, and glucocorticoids was determined by a competitive protein binding assay. Sampling at 4-hr intervals during 24 hr revealed diurnal changes in serum testosterone and glucocorticoids. Levels of testosterone were high throughout the night and low at the day time, conversely serum glucocorticoids were high levels in the morning and low in the evening. On the other hand, 30-min intervals sampling, serum testosterone levels decreased and glucocorticoids levels increased, respectively, immediately after the start of blood sampling. And then, low in testosterone and high in glucocorticoids levels were continually maintained. But serum LH levels had the pulsatile pattern and did not change markedly during 24 hr. After ACTH administration in five animals, serum glucocorticoids levels increased markedly and also testosterone levels increased slightly, but LH levels did not change. These data indicated that the every 30-min restraint stress caused the increment of glucocorticoids levels and the suppression of testosterone levels, but did not affect the serum LH levels. The increased glucocorticoids might inhibit the testicular steroidogenesis, without suppressing the LH secretion from the pituitary. PMID- 8462640 TI - [The change with age of the copulatory behavior of the male rats aged 67 and 104 weeks]. AB - Changes with age in sexual fertility in male rats of the Wistar-Imamichi strain were investigated. Litter size and numbers of implantation sites in females mated with males aged 14 to 44 weeks tended to decrease with increased aging of males. These indicators in females mated with males aged over than 44 weeks decreased, compared with that aged 14 to 44 weeks (P < 0.05 to 0.001). In addition, all females mated with males aged 95 weeks were not pregnant. In male copulatory behavior with aging, incidences and numbers of mounting at 67 and 104 weeks of age were 100%, 42.6 +/- 15.3 (Mean +/- S.D.) and 42%, 1.8 +/- 2.8, respectively. The intromission and ejaculation were observed at 67 weeks, but not at 104 weeks of age. These incidences and frequencies were 86%, 10.3 +/- 10.2 for intromission, and 43%, 1.0 +/- 1.3 for ejaculation. Mount latencies (ML) at 67 and 104 weeks of age were 535.4 +/- 607.9 and 3,822.0 +/- 1,753.4 sec, respectively. There were significant differences in ML between two groups (P < 0.05). At 67 weeks of age, intromission and ejaculation latencies, and post ejaculatory intervals were 2,563.0 +/- 2,216.3, 1,633.7 +/- 977.6, and 657.3 +/- 320.6 sec, respectively. The pregnant rate and numbers of implantation sites in females mated with males aged 67 weeks were 43% and 5.4 +/- 6.8, respectively. In females mated with males aged 104 weeks, all were not pregnant. The weights of tests, epididymides, ventral prostate and seminal vesicles at 104 weeks were light, compared with those at 67 weeks of age (P < 0.05). From these results, the copulatory behavior in male rats of the Wistar-Imamichi strain declined with aging. Sexual fertility in males aged 67 weeks decreased in less than 50%, and males aged 104 weeks showed no intromission and ejaculation. PMID- 8462641 TI - Genetic polymorphisms of salivary proteins in the rat. AB - Two genetic polymorphisms of salivary proteins were found by polyacrylamide gel electrophoresis among inbred strains of rats. Both proteins (RSP-1 and RSP-2) were inherited as a single autosomal trait. The loci were designated as Rsp-1 (rat salivary protein-1) and Rsp-2. Rsp-1 had two codominant alleles (Rsp-1a, Rsp 1b), and Rsp-2 had two alleles (Rsp-2a, and Rsp-2b); Rsp-2a was dominant over Rsp 2b. The Rsp-1 locus is not linked with the linkage groups (LGs) I, II, IV, V and the LGs containing Acp-2 and Pg-1. The Rsp-2 is not linked with the LGs I, II, V, X and the LGs containing Amy-1, Es-6 and Pg-1. PMID- 8462642 TI - Comparison of plasma endotoxin levels in germ-free, SPF and conventional laboratory animals (mice and rats). AB - Plasma endotoxin levels were examined in laboratory mice and rats sustained under germ-free (GF), SPF and conventional (CV) conditions. The values were 1.72 (GF mouse), 2.67 (SPF mouse), 2.44 (CV mouse), 2.05 (GF rat), 2.56 (SPF rat), and 3.13 pg/ml (CV rat). The GF animals showed the lowest levels, followed by SPF and CV animals, in that order. When SPF animals were transferred into the conventional condition (conventionalization), the plasma endotoxin levels changed slightly, but not significantly. The present study demonstrates that the levels of plasma endotoxin in healthy laboratory animals are relatively stable and are not affected by microbiological conditions. PMID- 8462643 TI - [On the flank gland in Syrian hamsters]. AB - The scent gland of Syrian hamsters is named the flank gland and thought to play an important role in the communication among individuals of the same species as in a few other rodents. In the present paper, the flank gland of Syrian hamsters of both sexes was macroscopically and histologically studied with special reference to the aging. This gland reached the plateau in size at 21 days of age in females, while it continued to develop until 70 days of age in males. Its shape was circular in adult females, and elliptical in adult males, respectively. Histologically, it was identified as the developing sebaceous glands with hair follicles in both sexes at 21 days of age. Thereafter, it gradually increased in size and number of lobules. It was always better developed in males than in females at each day examined in the present study, although there were no sex differences in its histological structure. PMID- 8462644 TI - [Comparison between the blood from orbital sinus and heart in analizing plasma biochemical values--increase of plasma enzyme values in the blood from orbital sinus]. AB - Plasma biochemical values, blood urea nitrogen (BUN), glucose, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), were compared between the samples collected from orbital sinus, heart and tail vein in mice, rats and hamsters. The significant higher values of AST, LDH and CPK were shown in samples from orbital sinus as compared with that from other sites. The blood from orbital sinus was bleeding by two methods and compared in the plasma enzyme values. It is suggested that the leakages of these enzymes from destroyed ocular tissues result in the increase of the plasma enzyme values. PMID- 8462645 TI - A study on diurnal fluctuation of blood-aqueous barrier permeability to plasma proteins. AB - The diurnal change of blood-aqueous barrier permeability to protein molecules was investigated in 20 eyes of 10 normal volunteers. Simultaneous determinations of aqueous flow rate and the coefficient of entry into the anterior chamber (k(in)) for plasma protein were performed at different times of the day: (a) 0800 to 1100 hr; (b) 1900 to 2200 hr of the same day; (c) 0800 to 1100 hr of the next day; (d) 1400 to 1700 hr 1 week later; and (e) 0200 to 0500 hr of the following morning. Aqueous flow rate was determined by fluorophotometry and k(in) was calculated for each period from flow rate, plasma protein concentration, anterior chamber volume and aqueous protein concentration measured with a laser flare-cell meter. Calculated values for k(in) did not fluctuate significantly among the periods, and there were no significant changes in anterior chamber volume or plasma protein concentration. Aqueous protein concentration and flow rate showed diurnal fluctuations, the patterns of which inversely corresponded to each other. It was concluded that permeability of the blood-aqueous barrier to protein remains fairly stable over a 24-hr period and the diurnal variation of aqueous protein concentration is mostly attributable to that of aqueous flow rate. PMID- 8462646 TI - Effects of ciliary ganglionectomy on contractile responses in the dilator muscle of the rat iris. AB - Effects of removing the ciliary ganglion (CGR) on contractile responses of the rat iris dilator muscle to agonists were examined and compared with those after removing the superior cervical ganglion (SCGR). Denervations were considered successful if the atropine or phentolamine-sensitive mechanical responses to transmural nerve stimulation were abolished. After CGR, muscle sensitivity to noradrenaline (NA) increased two to three times in terms of their ED50, whereas the ED50 for methoxamine did not change. The sensitivity of both the control and denervated dilator muscles to NA increased after treatment with 30 microM cocaine, and resulted in similar ED50s. The content of NA in the whole iris decreased by about 27% after CGR. Maximal responses of the dilator muscle to NA and 5-hydroxytryptamine were significantly increased by CGR, but decreased by SCGR. These results indicate that sympathetic post-ganglionic nerves running through the CG and short ciliary nerves contribute about 27% of the total sympathetic innervation of the iris region. The CGR, therefore, induced a small presynaptic supersensitivity specific to NA. The non-specific increase in the maximal responses to agonists after CGR may be attributable to a parasympathetic denervation since sympathectomy by SCGR decreased the maximal responses. PMID- 8462647 TI - Polylysine stimulated protein phosphorylation in rabbit ciliary processes: casein kinase activities. AB - Protein phosphorylation in response to polylysine was investigated in vitro in rabbit ciliary process homogenates by SDS-PAGE autoradiography. The degree of phosphorylation was greater in the soluble/cytoplasmic fraction than in the particulate fraction and was antagonized by heparin. Time and dose-dependent studies indicated several different kinetic patterns of phosphorylation/dephosphorylation among the approximately 15 significantly 32P labeled bands found in each fraction. These results are consistent with phosphorylation of endogenous substrates by casein kinase II, and dephosphorylations by type I and type II phosphoprotein phosphatase enzymes. The presence of EGF receptors in ciliary processes was indicated by high affinity (kD < 0.5 nM) binding sites and by intraocular pressure and blood-aqueous barrier responses to injection of low doses of EGF (100 ng per eye). EGF did not stimulate protein phosphorylation in ciliary process homogenates in vitro. The results show that casein kinase II is a significant kinase activity in ciliary processes and may have a modulatory role on signal transduction proteins involved in cellular response to hormones. PMID- 8462648 TI - Comparative studies on fatty acid composition and phospholipases A2 and C activities in rabbit and bovine iris-ciliary body. AB - It is well established that production of prostaglandins by ocular tissues is dependent upon the species. The rabbit iris-ciliary body produces greater amounts of prostaglandins than that of the bovine. To throw more light on the biochemical basis underlying these differences we have compared the fatty acid composition and phospholipases A2 and C activities in rabbit and bovine irides. When the concentration of arachidonic acid is expressed as % of total fatty acids, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, separated from rabbit iris phospholipids, contained 56, 38 and 18% more arachidonic acid, respectively, than those of the bovine. The total lipid phosphorus in rabbit and bovine iris-ciliary body were found to be 13.74 and 9.34 mumol g-1 wet tissue, respectively. Subcellular fractions, prepared from rabbit iris, contained 30-230% more phospholipase C activity than those of the bovine, and about 5-41 times higher phospholipase A2 activity than those of the bovine. In the rabbit iris microsomal fraction, phospholipase C activity is 33 times higher than that of phospholipase A2. However, the data presented suggest that phospholipase A2, rather than phospholipase C, is the enzyme which is more involved in arachidonic acid release for eicosanoid biosynthesis. These findings suggest that the high contents of arachidonic acid and phospholipases A2 and C in the rabbit iris could contribute to its unique capacity to synthesize and release prostaglandins in the anterior segment as compared to that of other mammalian species. PMID- 8462649 TI - A soluble product of human corneal fibroblasts inhibits lymphocyte activation. Enhancement by interferon-gamma. AB - Corneal stromal fibroblasts expressed HLA-DP, -DQ and -DR Class II MHC antigens in response to interferon-gamma, but did not induce proliferative responses by allogeneic peripheral blood mononuclear cells in vitro when used as stimulator cells in a mixed leukocyte-type reaction. Furthermore, corneal stromal fibroblasts inhibited mixed leukocyte reactions between peripheral blood mononuclear cells of allogeneic donors, even when the corneal stromal fibroblasts were separated from the peripheral blood mononuclear cells by a 0.4 micron pore membrane. Pretreatment of the corneal stromal fibroblasts with interferon-gamma increased the inhibitory activity. Both [3H]thymidine incorporation and interleukin-2 production were inhibited, and the inhibition appeared to be mediated by a soluble factor whose production required protein synthesis. The inhibitory activity was not abolished by including 1-10 micrograms ml-1 indomethacin in the culture media. No inhibition was observed in the proliferation dose-response curves of responder peripheral blood mononuclear cells that had been cultured with corneal stromal fibroblasts for 3 days, prior to culture with allogeneic stimulator peripheral blood mononuclear cells. Thus, the ability of corneal stromal fibroblasts to interfere with alloimmune responses in vitro was dependent upon the continued presence of the fibroblasts and their continued production of a soluble inhibitory factor or factors. Inhibitors of allogeneic reactions that are produced by corneal stromal fibroblasts stimulated by immune cytokines (e.g. interferon-gamma) may play a role in prolonging corneal allograft survival. PMID- 8462650 TI - Uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis in the Lewis rat: an ultrastructural study. AB - The histopathological features of uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis (EAE) were investigated using light and electron microscopy. Lewis rats were immunized by spinal cord homogenate, complete Freund's adjuvant and Bordetella pertussis. The eyes of rats with EAE exhibited vasculitis in the iris, trabeculitis and endothelial abnormalities in the retinal vessels; vasculitis was observed in the optic nerve and brain. Endothelial cells in the vessels in the iris, retina, optic nerve and central nervous system were noted to be elevated (high endothelial-like venules, or HELV). Inflammatory cells in the vascular lumen were attached to the surface of endothelial cells in abnormal areas in the iris. By comparison with the findings in the iris and retina, there were no significant changes in the vessels of the ciliary body and choroid. The ultrastructural features indicated that anterior uveitis in acute EAE resulted from vasculitis in the iris due to changes of the endothelial cells and was not due to a reaction against the myelinated nerves or any other particular components of the iris. In addition, our results suggested that vasculitis in the iris was consequent upon specialized changes of the endothelial cells similar to HELV which were responsible for the transcellular emigration of lymphocytes in other inflammatory diseases or in experimental models. HELV change plays an important role in the perivascular inflammatory process in the iris, retina, optic nerve and central nervous system in EAE and possibly in multiple sclerosis. PMID- 8462651 TI - Glycation mediated lens crystallin aggregation and cross-linking by various sugars and sugar phosphates in vitro. AB - Glycation of lens crystallins results in protein conformational changes, oxidation, browning and aggregation. Though glucose is the major sugar, other sugars and sugar phosphates generated as intermediates of metabolic pathways are present in the lens, albeit at low concentrations. In this study we incubated bovine lens soluble fraction with various sugars and sugar phosphates (5mM for 10 days). The reactivity was in the order trioses > tetroses > pentoses > hexoses. High molecular weight (HMW) aggregates were also formed at a comparable rate. Increased levels of fluorescence were associated with the HMW aggregates with fast reacting sugars. The phosphorylated derivatives were only slightly more reactive than their respective sugars. Interestingly, fructose-1,6-diphosphate was more reactive and cross-linked more readily than fructose-6-phosphate. Gel electrophoresis under reducing and nonreducing conditions showed formation of disulfide linked protein aggregates with slow reacting sugars such as glucose and non-disulfide covalent linked protein aggregates with fast reacting sugars such as erythrose. In contrast, if 0.1 m DTT was present in erythrose incubations (a fast reacting sugar), the HMW aggregate formation was significantly reduced. In order to show the reactivity among the slow reacting hexoses, we incubated lens proteins with 1 M hexoses for 30 days and the results showed that galactose was more reactive and showed higher cross-linking than fructose and glucose. These results thus indicate that relatively low levels of some sugars and sugar phosphates in the lens could be compensated by enhanced lens protein cross linking and the combined effect could be rather significant with respect to cataractogenesis. PMID- 8462652 TI - Modelling cortical cataractogenesis. 13. Early effects on lens ATP/ADP and glutathione in the streptozotocin rat model of the diabetic cataract. AB - A possible contribution to cell toxicity in the diabetic lens due to early ATP loss is not well characterized prior to the appearance of vacuoles in the lens. Changes in lens ATP levels at longer periods of hyperglycaemia (6-8 weeks) have been reported. We used [31P]NMR analysis of lens extracts at three time periods, comparing diabetic to concurrent control groups at 1, 2 and 4 weeks of hyperglycaemia. With this design, significant alterations (> 10%) in the ATP/ADP ratio can be monitored. NMR analysis revealed a decreased ATP/ADP ratio at all time periods, averaging a 38% decrease. Luminescent determination of ATP levels indicates that this decrease is mainly caused by a decrease of 25% in ATP concentration. The early loss of GSH was large and not accompanied by an appearance of GSSG, as monitored by HPLC electrochemical detection. A 1-week experiment with animals receiving daily insulin treatment was carried out to control for effects of STZ on the lens. This treatment resulted in normal lens GSH levels and a near normal [31P]NMR profile. PMID- 8462653 TI - Changes in the retinal ganglion cell layer and optic nerve of rats exposed neonatally to cocaine. AB - The effects of neonatal exposure to cocaine upon the structure of the visual system are poorly understood despite the evidence of eye abnormalities in infants exposed in utero to cocaine. We previously demonstrated alterations in the optic nerve of rats exposed neonatally to cocaine, although no changes were detected in the number of its axons. This study was undertaken to investigate the retinal ganglion cell layer and the size distribution of the optic axons, in an attempt to assess further changes in the visual pathways. Groups of rats (Wistar strain) were given subcutaneous injections of cocaine hydrochloride (15 mg kg-1 body weight day-1) divided into two daily doses, from the day following birth until postnatal day 30 Controls were given subcutaneous saline throughout the same experimental period. Per group, five animals from three different litters were evaluated morphometrically. Following perfusion with aldehydes, samples from the median ventral and dorsal parts of the retina and the optic nerves were processed for electron microscopy. Morphometric techniques at light and electron microscopic levels allowed us to determine the following. (a) In the optic nerve: (1) frequency size-distribution of myelinated nerve fibres; and (2) number of myelin sheaths per fibre. (b) In the retina: (1) thickness of the layers; (2) frequency size-distribution of ganglion layer neurons; (3) mean cell nuclear size; and (4) packing density of ganglion cell layer neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462654 TI - Features of the polarity of the Golgi apparatus of frog photoreceptors: studies with lectins and with Brefeldin A. AB - The cis-trans polarity of the Golgi apparatus is important in Golgi functioning in glycosylation, sorting and other processes. The present work extends our prior studies on the polarity of the Golgi apparatus of frog (Rana) rod photoreceptors. We demonstrate that Golgi structures with the morphology and distribution of cis elements show the heaviest deposition of osmium. Elements with morphology and cytochemical reactivities resembling trans Golgi structures remain discernible as discrete arrays after exposure of the cells to Brefeldin A. These properties strengthen our identification of cis and trans elements since they are shared with corresponding Golgi structures in other cell types. We have also investigated the binding of lectins to sections prepared by cryoultramicrotomy. We find that Concanavalin A, with probable chief affinity for core mannoses in oligosaccharides, localizes to cis, medial and trans elements of the photoreceptor's Golgi apparatus. Wheat germ agglutinin, with likely affinity at least partly for terminal N-acetylglucosamines, localizes to trans and medial elements. A trans localization is seen with Ricinus communis agglutinin (RCA 120), but this lectin binds extensively only after neuraminidase treatments suggesting that its chief affinity is for galactose residues that are penultimate to sialic acids (neuraminic acids) in the native oligosaccharides. Overall, the pattern of lectin binding to Golgi structures that we observe resembles that seen in a variety of other cell types. The distribution of glycosylated molecules we detect in the photoreceptor's Golgi apparatus may bear upon such matters as the unusual features of the glycosylation of mature opsin. PMID- 8462655 TI - Immunocytochemical identification of serotonin-synthesizing neurons in the vertebrate retina: a comparative study. AB - Serotonin-synthesizing neurons in the retinas of goldfish, axolotl, turtle, chick, rabbit and cat were identified using double labelling with anti-serotonin and anti-phenylalanine hydroxylase antibodies. The latter antibody recognizes tryptophan 5-hydroxylase, one of the synthesizing enzymes for serotonin. Neurons labelled by both markers were considered to be serotonin-synthesizing neurons, while those only with serotonin-immunoreactivity were assumed to be serotonin accumulating neurons. In the goldfish and chick retinas, all serotonin immunoreactive amacrine cells (S1) were positive for phenylalanine hydroxylase. In the axolotl and turtle retinas, all the S1 amacrine cells, and only 52.8% and 40.5% of S2 amacrine cells were double-labelled. Although serotonin immunoreactive bipolar cells were observed in the turtle and chick retinas, the synthesizing enzyme for serotonin could not be detected in these cells. In the rabbit and cat retinas, tryptophan hydroxylase could not be revealed in any cell type with immunocytochemistry. In control experiments SLI neurons in the raphe nuclei of the brain stem always exhibited PH-LI in all species examined, including mammals, indicating that our anti-PH antibody is able to recognize tryptophan hydroxylase across vertebrate classes. These results indicate that the majority of serotonin-immunoreactive amacrine cells are able to synthesize serotonin and are the source of endogenous serotonin in the non-mammalian retina, while some serotonin-immunoreactive amacrine and bipolar cells possibly only accumulate serotonin. We also suggest that serotonin may not be a primary neurotransmitter in the serotonin-accumulating bipolar and amacrine cells of the non-mammalian retina. PMID- 8462656 TI - Intercellular adhesion molecule-1 on rat corneal endothelium in experimental uveitis. AB - We studied the expression of the intercellular adhesion molecule-1 (ICAM-1) on the corneal endothelium of the rat in the experimental uveitis induced by interphotoreceptor peptides (R-4) as an immunogen using immunohistochemical methods. ICAM-1, which was not detected in eyes without inflammation, was expressed on the corneal endothelium, vascular endothelium and inflammatory cells, such as monocytes and lymphocytes, in R-4 induced uveitis. The ocular inflammation in the iris, ciliary body and anterior chamber associated with the adherence of inflammatory cells to the corneal endothelium (keratic precipitates) first appeared on the 11th day and were most remarkable on the 14th day and then gradually subsided after 18th day. The expression of ICAM-1 on the corneal endothelium was noticed from the 12th day of immunization to the 16th day and was most prominent on the 14th day but disappeared after the 18th day. The present study proved that ICAM-1 was expressed on the corneal endothelium in anterior uveitis and further indicated that the corneal endothelium modulates the inflammation of the anterior ocular segment by expressing ICAM-1 and forming keratic precipitates. PMID- 8462657 TI - The hematopoietic deficiencies in osteopetrotic (op/op) mice are not permanent, but progressively correct with age. PMID- 8462658 TI - Optimal erythroid cell production during erythropoietin treatment of mice occurs by exploiting the splenic microenvironment. AB - In this study, quantitative effects on erythroid cell production by a prolonged recombinant human erythropoietin (rhEpo) treatment of mice are presented. Epo treatments, given subcutaneously (s.c.) twice per day in doses of 0.5 to 500 U per day, were performed under steady-state production conditions. We found striking differences between the behavior of the different erythroid cell compartments (burst-forming unit erythroid [BFU-E], colony-forming unit erythroid [CFU-E] and erythroid precursors), as well as between the microenvironments of bone marrow and spleen. Whereas the total-body BFU-E was not changed by Epo, a redistribution of BFU-E from marrow to spleen occurred, resulting in decreasing marrow and increasing splenic BFU-E numbers. Splenic BFU-E produced CFU-E as much as 8 times more efficiently than marrow BFU-E at 50 U of Epo. At low Epo doses (to 1 U/day) no difference was found. The CFU-E in the spleen produced erythroblasts at a higher efficiency at all Epo doses (1.5 to 5 times). It seems as if this efficiency was higher at low Epo doses. Because of the migration phenomenon and the excellent microenvironment in the spleen, at the highest Epo concentrations nearly 70% of all erythroid cells reside in the spleen. Even at the highest Epo doses, granuloid cell production was not affected. Similar to the BFU-E, total-body granuloid cells remained constant (despite a shift of granulocyte-macrophage progenitors [CFU-GM]) from marrow to spleen; however, these cells did not flourish in the spleen. Under these conditions, 90% of the granuloid precursors were still localized in the marrow. Erythropoietin did not change the transit time of erythroid cells at high Epo doses. PMID- 8462659 TI - Regulation of myelopoiesis by murine fibroblastic and adipogenic cell lines. AB - The regulation of hematopoiesis has been suggested to take place in close association with various cell types found in the bone marrow (BM) microenvironment. In the present study the role of fibroblasts, adipocytes and cell surface heparan sulfate in regulating hematopoiesis in an in vitro mouse system was examined. Mouse BM cells were allowed to adhere to a mouse embryo fibroblast cell line (C3H 10T1/2) or a clonally derived adipogenically determined derivative (Clone D) of the 10T1/2 cell line. Nonadherent cells were removed, cultures were overlaid with semisolid media supplemented with growth factors and colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and multipotential (CFU-GEMM) progenitor cells was quantitated. Adherence and co culture of BM cells with the fibroblast cell line resulted in increased numbers of total CFU-GM and CFU-GEMM colonies. In contrast, adherence and co-culture of BM cells with the adipocytic cell line resulted in an increase only in CFU-GEMM colonies. Morphological analysis revealed a preferential adherence/growth of granulocyte and macrophage progenitors at the expense of bipotent granulocyte macrophage progenitors to the fibroblastic cell line and an increase in the adherence/growth of granulocyte progenitors to the adipogenic cell line. Progenitor cell adherence was abolished when the fibroblastic or adipocytic cell lines were pretreated with heparitinase. These results demonstrate enhanced proliferation/differentiation of hematopoietic progenitor cells when there is direct contact between hematopoietic progenitors and cell types characteristic of those found in the microenvironment and that heparan sulfate and different types of stromal cells appear to play different roles in this interaction. PMID- 8462660 TI - Preparation of a monoclonal antibody directed against the receptor for murine colony-stimulating factor-1. AB - Studies were undertaken to produce monoclonal antibodies directed against the murine receptor for macrophage colony-stimulating factor (M-CSF or CSF-1). Sprague-Dawley rats were injected with lysates prepared from a murine myelomonocytic cell line (RAW cell line) that has high levels of M-CSF receptors. Spleen cells from immunized animals were fused with murine plasmacytoma cells and expanded. Supernatants from these cells caused inhibition of 125I-CSF binding to either RAW cells or normal murine marrow cells. Antibody-producing cells were cloned by limiting dilution and by colony growth in agar. The antireceptor antibodies appear specific as they neutralize colony formation by M-CSF but have little or no effect on colony growth in response to the other hemopoietic growth factors granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin 3 (IL-3) or erythropoietin. These antibodies should aid in defining the role of M CSF in hemopoiesis in vivo. PMID- 8462661 TI - Molecular evolution of cytokines and their receptors. PMID- 8462662 TI - Induced myeloid differentiation of K562 cells with downregulation of erythroid and megakaryocytic transcription factors: a novel experimental model for hemopoietic lineage restriction. AB - The human erythroleukemia cell line K562 can be induced to differentiate along the erythroid and megakaryocytic lineages. Here we demonstrate that hexamethylene bisacetamide (HMBA) induced K562 cells to differentiate along a third pathway. This was accompanied by downregulation of two transcription factors normally expressed in erythroid, mast and megakaryocyte lineages. Northern analysis demonstrated coordinate downregulation of alpha globin and gamma globin in addition to the two lineage-restricted transcription factors, SCL and GATA-1. Proliferation of the K562 cells was also suppressed. Clonal assay showed that the suppression was irreversible and appeared analogous to the commitment of murine erythroleukemia (MEL) cells to terminal differentiation. In contrast to MEL cells, however, K562 cells acquired a macrophage-like morphology and exhibited a complete failure to generate benzidine-positive cells. Electron microscopy revealed a marked increase in granules resembling those specific for eosinophils. Surface marker analysis showed that HMBA-induced cells expressed reduced levels of glycophorin A, CD5, CD7 and CD11b. No upregulation of megakaryocyte or lymphoid markers occurred. Thus the response of K562 cells to HMBA may provide a useful experimental system for studying the molecular mechanisms responsible for downmodulation of lineage-restricted transcription factors during hemopoietic lineage commitment. PMID- 8462663 TI - Establishment of bone marrow-derived macrophage cell lines by soft-agar cloning: regulation of macrophage heterogeneity at bone marrow level. AB - To study the regulation of macrophage (m phi) heterogeneity at bone marrow level, we developed a liquid culture system in which bone marrow-derived soft-agar colonies were expanded in the presence of colony-stimulating factor-1 (CSF-1). Several cloned m phi precursor cells were established as CSF-1-dependent cell lines, and were analyzed for morphological, phenotypic and functional characteristics. The continuously proliferating cell lines expressed both immature and mature m phi markers. Only minor differences between the established cell lines were detected. Thus, our results show that during long-term culture CSF-1-responsive cloned m phi precursor cells develop along identical pathways, giving rise to progeny with comparable phenotype and function in vitro. PMID- 8462664 TI - Circadian variations in myelosuppressive activity of interferon-alpha in mice: identification of an optimal treatment time associated with reduced myelosuppressive activity. AB - A number of antitumor drugs have been shown to vary in their toxicity and in their antitumor potency according to the time in the circadian cycle at which they are administered. It was of interest to determine whether other agents, such as a biological response modifier, would also exhibit differential potency during the circadian cycle. Interferons (IFNs) are biological response modifiers which have antitumor and antiviral activity and which also have toxic side effects. A mouse model was used to study one of these toxic side effects, peripheral white blood cell (WBC) suppression. Interferon-induced peripheral WBC suppression was evaluated as a function of the time of recombinant human (rh) IFN-alpha A/D administration. Mice were maintained on cycles of 12 hours of light and 12 hours of darkness. The rhIFN-alpha A/D was administered at various hours after light onset (HALO). The rhIFN-alpha A/D-induced peripheral WBC suppressive effect varied in its intensity in a cyclical manner. Administration of rhIFN-alpha A/D at 0 HALO caused the greatest suppressive effect, while administration of rhIFN alpha A/D at 8 HALO caused the least suppressive effect. Mice treated at 8 HALO were found to be about 10-fold less sensitive to the peripheral WBC suppressive effects of rhIFN-alpha A/D than mice treated at 0 HALO. This differential sensitivity to the peripheral WBC suppressive effects of rhIFN-alpha A/D was examined for 6 different times in the circadian cycle and was found to be a general effect, occurring throughout the circadian cycle. Using a granulocyte/macrophage colony-forming unit (GM-CFU) assay, bone marrow function was also shown to be differentially affected by treatment with rhIFN-alpha A/D at 0 HALO and 8 HALO in a manner parallel to that seen with peripheral WBC. Thus, rhIFN-alpha A/D exerts a differential effect on peripheral WBC counts and on bone marrow function according to the time in the circadian cycle at which it is administered to the mouse. Such temporal variation in the myelosuppressive activity of interferons could be important in designing future clinical trials with these antiviral and antitumor agents. Administration of interferons at empirically determined times in the circadian cycle could be used to reduce the myelotoxic side effects of interferons in humans. PMID- 8462665 TI - Identification of an alternatively spliced transcript of human interleukin-4 lacking the sequence encoded by exon 2. AB - The expression of interleukin-4 (IL-4) mRNA of human peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA) for 15 hours was analyzed by reverse transcription and subsequent polymerase chain reaction (RT/PCR). These analyses revealed an additional smaller fragment that hybridizes with an IL-4 cDNA probe and an oligonucleotide that is specific for a fragment lacking the sequence encoded by exon 2. Sequencing of this fragment demonstrates that it is generated from an alternatively spliced transcript of the IL-4 gene with the sequence encoded by exon 2 being skipped. Skipping of exon 2 does not result in a frame shift but would delete part of the mature protein (48 bp coding for amino acid residues 22 to 37), including Cys24 but not a region directly involved in receptor binding. Differential splicing of other exons or exon combinations has not been observed. The data suggest that the alternatively spliced transcript is not generated by a splicing or PCR error and is not detectable solely because of the high sensitivity of RT/PCR, but in contrast, argue for a physiological role of the transcript and its potentially encoded protein. PMID- 8462666 TI - Spectrophotometric determination of clonogenic capacity of leukemic cells in a semisolid microtiter culture system. AB - In this study we describe a semiautomated clonogenic assay in which human leukemic cell lines (U937 and HL60) are cultured in a semisolid 96-well microtiter culture system and clonogenicity is measured spectrophotometrically in a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT)-assay and sulforhodamine (SRB)-assay. Culture medium with 0.6% (wt/vol) methylcellulose and 10% (vol/vol) fetal calf serum (FCS) appeared to provide optimal culture conditions with a low background absorbance in both colorimetric assays and an optimal linearity between cell number and optical density (OD). An excellent correlation between clonogenic growth of U937 and HL60 cells in the conventional colony-forming unit assay (CFU-assay) and the microtiter CFU-assay was observed. The value of this microtiter CFU-assay was assessed by modulating U937 and HL60 cells with either 1,25(OH)2D3 or cytosine arabinoside (Ara-C). Additionally, the number of living cells was quantitated spectrophotometrically in both MTT- and SRB-assays. Results obtained by either method did not differ significantly (p < 0.001). In liquid culture, however, significantly (p < 0.001) less reduction of cellular growth was observed with 1,25(OH)2D3-modified cells. No significant differences between the liquid and semisolid assay systems could be observed in the presence of Ara-C. In conclusion, the microtiter clonogenic assay provides a rapid and objective way of measuring clonogenic capacity of (leukemic) cell lines. The semiautomated clonogenic assay will be useful to assess large series of immune modulations and/or cytostatic drug screening. PMID- 8462667 TI - DNA ploidy and cell kinetic characteristics in canine non-Hodgkin's lymphoma. AB - Malignant lymphoma in the dog is frequently postulated and used as a therapeutic model for non-Hodgkin's lymphoma (NHL) in humans. In this study DNA ploidy and the cell kinetic characteristics of canine malignant lymphoma were studied by flow cytometric (FCM) nuclear DNA measurements on fresh frozen tumor tissue from 94 dogs with NHL and on material from non-neoplastic lymph nodes from 20 dogs. The results were correlated with histomorphology, immunophenotype and survival. All non-neoplastic tissues were diploid, whereas of the 94 lymphomas 74 were diploid or near-diploid and 20 aneuploid. Of the aneuploid lymphomas, 1 contained a hypoploid cell population. DNA-indices of the aneuploid peaks ranged from 0.87 to 1.21 (mean 1.11). The mean S-phase fraction (8.2%, SD 4.8) was significantly lower in the non-neoplastic tissues than in the lymphomas (11.4%, SD 5.1). A linear correlation was observed between FCM S-phase fractions and bromodeoxyuridine (BrdU) labeling indices (r = 0.78; p < 0.001) determined in paraffin-embedded tissue sections from 18 dogs with NHL after in vivo BrdU labeling. DNA ploidy status did not correlate to the S-phase fraction. There were no differences in S-phase fraction and DNA ploidy between B cell and T cell lymphomas or between different histological classes using the Working Formulation. No correlation was found between S-phase fraction or DNA ploidy and survival in a series of 59 dogs treated with a combination chemotherapy protocol. It is concluded that the frequency of DNA aneuploidy in canine malignant lymphoma is similar to that in human NHL. In contrast to findings in human NHL, however, no relationship was found between DNA ploidy or cell kinetic features and histomorphology or prognosis. PMID- 8462668 TI - How does the switch II region of G-domains work? AB - The transition of guanine nucleotide binding proteins between the 'on' (GTP bound) and 'off' (GDP-bound) states has become a paradigm of molecular switching after a chemical reaction. The mechanism by which the switch signal is transmitted to the downstream recipients in the intracellular signal pathway has been extensively studied by biochemical, biophysical and genetic methods, but a clear picture of this process has yet to emerge. Based on the similarities of ras p21 and elongation factor Tu we propose here a model of the GDP state of ras-p21 that is in agreement with all relevant experimental evidence. The model provides important clues about: (1) a possible molecular mechanism for signal transmission from the site of GTP hydrolysis to downstream effectors; (2) a major conformational change during signal generation and a key residue involved in this process (Tyr-64); and (3) regions in ras-p21 that can be differentially recognized by binding to external partners in a GTP/GDP state dependent fashion, most notably residues D69, Q70, R73, T74, R102, K104, D105 at the end of the alpha-helices 2 and 3. PMID- 8462669 TI - Crystal structure of a distal site double mutant of sperm whale myoglobin at 1.6 A resolution. AB - The three-dimensional structure of sperm whale myoglobin His64(E7)- >Val,Thr67(E10)-->Arg double mutant has been studied by X-ray crystallography at 1.6 A resolution, and refined to a crystallographic R-factor of 0.197. The Arg67(E10) side chain is extended in the direction of the ligand binding site, and its NH1 atom is at a distance of 3.11 A from the NH1 atom of Arg45(CD3), which is also pointing towards the distal site. Both are kept in this position by hydrogen bonding and electrostatic interactions with a solvent sulfate ion, located amongst the two, on the protein surface. No liganded water molecule is present at the sixth coordination position of the Fe(III) heme. PMID- 8462670 TI - Chemical crosslinking studies of the isolated light-harvesting B800-850 complex of Chromatium minutissimum. AB - The spatial relationship of polypeptides comprising the light-harvesting B800-850 complex of Chromatium minutissimum has been studied by means of chemical crosslinking of the isolated complex with cleavable, 1.2 nm-long dithiobis(succinimidyl propionate). The samples were analyzed by different types of electrophoresis and spectrophotometrically. No difference was shown between crosslinking of the B800-850 complex either solubilized or incorporated into proteoliposomes. It was found that two main polypeptides form only one type of heterodimer. The crosslinked complex was more thermostable. This crosslinkage restricted the conformational transitions causing the shift of the long wavelength band in the near infrared region. A structure of the complex is discussed. PMID- 8462671 TI - Expression of a pokeweed antiviral protein in Escherichia coli and its characterization. AB - Two expression vectors were constructed to produce a putative mature alpha pokeweed antiviral protein (alpha-PAP) in Escherichia coli with its NH2- and COOH terminal extrapeptides excised. One was for its intracellular expression with a methionine at its NH2-terminal. The other was for its secretion using an ompA signal peptide. The former product was purified from the total soluble proteins of the transformant with a yield of 1.74 mg/liter and the latter had a yield of 5.55 mg/liter. Both products exhibited RNA N-glycosidase activity on wheat ribosomes and inhibitory activity to protein synthesis in a rabbit reticulocyte system. PMID- 8462672 TI - Amino acid sequence of alkaliphilic serine protease from silkworm, Bombyx mori, larval digestive juice. AB - Alkaliphilic protease, P-IIc, from silkworm, Bombyx mori, larval midgut digestive juice consists of 232 amino acids. It has a catalytic triad, Asp-His-Ser, invariably found in a serine protease. A shift of optimal pH value towards the alkaline side diminished at mu = 1.0. This suggests the existence of an electrostatic interaction that affects the proteolytic activity. The higher Arg content may be responsible for this phenomenon. Two cysteine residues probably exist unpaired in a novel position among serine proteases. PMID- 8462673 TI - Differentiation-associated expression of prostaglandin G/H synthase in monocytic cells. AB - Significant progress in the investigation of the regulation of prostanoid formation has recently been made by cloning a second gene coding for prostaglandin G/H synthase (PGHS; EC 1.14.99.1). In this study we examined the expression of the two PGHS isoforms during phorbol ester induced monocytic differentiation of human myeloid leukemia cells (U937). Murine and ovine PGHS-1 probes hybridized to 2.8- and 5.5-kb mRNA species, whereas the murine PGHS-2 probe hybridized to a 5.3-kb species. Western blot analysis using antisera to mouse PGHS-1 and to a synthetic peptide derived from a mouse PGHS-2-specific region revealed a band of 70 kDa for PGHS-1 and a doublet of about 85 kDa for PGHS-2. Unlike PGHS-2, which was not expressed in U937 control cells, both PGHS-1 protein and mRNA were detected in untreated U937 cells. TPA strongly induced PGHS 2 protein and also increased the amount of PGHS-1 protein. Correspondingly, a marked induction of PGHS-2 mRNA was found, but virtually no change in the expression of the PGHS-1 2.8-kb mRNA occurred. The induction of both PGHS isoforms turned out to be dexamethasone-sensitive. The suppression of PGHS-2 induction was more pronounced. These results suggest that both PGHS-1 and to a larger extent PGHS-2 contribute to the upregulation of prostanoid synthesis during monocytic differentiation. PMID- 8462674 TI - Primary structure determination and cloning of the cDNA encoding toxin 4 of the scorpion Centruroides noxius Hoffmann. AB - A peptide (toxin II-10), shown to be a Na+ channel blocker, was purified from the venom of the scorpion Centruroides noxius Hoffmann and sequenced by Edman degradation. It has 66 amino acid residues with the C-terminal residue (asparagine) amidated, as demonstrated by mass spectrometry. In addition, we report the cloning and the nucleotide sequence of the cDNA (CngtV) that codes for this toxin. We discuss the mechanism for processing the precursor peptide to its final form and compare the primary structure to that of other Na+ channel toxins. Two distinct groups of toxins seem to emerge from this comparison, suggesting a structure-function relationship of these peptides towards the recognition of either mammalian or insect tissues. PMID- 8462676 TI - Purification and partial characterisation of NADP(+)-linked isocitrate dehydrogenase from rat liver cytosol. AB - NADP(+)-linked isocitrate dehydrogenase from rat liver cytosol was purified (approximately 135-fold) to apparent homogeneity in 27% yield. The purified enzyme has specific activity of 73 units.mg-1. The native enzyme showed an apparent M(r) of 94,000 by gel filtration and was composed of two identical subunits of M(r) 45,000 as judged by SDS/PAGE. In isoelectric focusing, a pI value of 5.7 was estimated for the enzyme. PMID- 8462675 TI - Potentiation of diacylglycerol-induced activation of protein kinase C by lysophospholipids. Subspecies difference. AB - Lysophospholipid, particularly 2-lysophosphatidylcholine (lysoPtdCho), significantly potentiates the diacylglycerol (DAG)-induced activation of protein kinase C (PKC) in vitro. LysoPtdCho shows no effect, unless DAG and phosphatidylserine (PtdSer) are present. This lysoPtdCho action also depends on its own as well as on Ca2+ concentration. At physiological Ca2+ concentrations, the activation of the alpha-, beta-, and gamma-subspecies (cPKC) is enhanced by lysoPtdCho in the 10(-6) M range, but inversely inhibited in the 10(-5) M range. The delta- and epsilon-subspecies (nPKC), which are enzymatically insensitive to Ca2+, are mostly inhibited by lysoPtdCho at its low concentrations. The enhancement of cPKC activation by lysoPtdCho is due to the increase in an apparent affinity of the enzyme for PtdSer but not for DAG. The results may account, at least in part, for the previous observations made with intact cell systems that lysoPtdCho significantly potentiates the DAG-induced cellular responses such as T-lymphocyte activation and HL-60 cell differentiation [(1992) Trends Biochem. Sci. 17, 414-417]. PMID- 8462677 TI - Structure of the nuclear encoded gamma subunit of CF0CF1 of the diatom Odontella sinensis including its presequence. AB - Using a PCR-product as homologous probe for screening of a cDNA library of the diatom Odontella sinensis overlapping cDNA clones were obtained which showed homologies to atpC-genes of F0F1-ATPases from different sources. Comparison of the deduced amino acid sequence with the N-terminal sequence of the Odontella gamma subunit obtained by protein sequencing, indicated that the complete 370 amino acid protein is processed to a mature protein of 315 amino acids. The 55 amino acids comprising the presequence consists of two segments, one resembling a signal sequence for cotranslational transport through ER membranes and one showing characteristics of a transit sequence for transport of proteins into chloroplasts of higher plants. This result is discussed with respect to the particular envelope structure of chromophytic plastids consisting of four membranes. The outer membrane contains ribosomes on its cytosolic surface. As in cyanobacterial gamma subunits the regulatory sequence region, which is involved in thiol modulation of chloroplast ATPase of green algae and higher plants, is absent in the Odontella gamma subunit. PMID- 8462678 TI - Purification and properties of a 155 kDa bone marrow-derived glycoprotein enhancing the activity of granulocyte-macrophage colony stimulating factor (GM CSF). AB - A protein has been purified from pig bone marrow which enhances the activity of exogenously added granulocyte-macrophage colony stimulating factor (GM-CSF) on mouse myelopoietic colony formation in vitro. The substance alone did not exhibit any colony stimulating activity. The active fraction was isolated from the medium of pig bone marrow suspension cultures during 20-24 h. Purification to homogeneity was then performed by subsequent HPLC and SDS-PAGE. The GM-CSF enhancing protein was identified as a 155 kDa glycoprotein. PMID- 8462679 TI - NO, thiols and disulfides. AB - The chemical nature of the messenger molecule, nitric oxide (NO), and especially its reactivity towards thiol groups and disulfides, could explain, at least partly, its intervention in so many different biological processes. NO can be regarded as the smallest molecule suitable for electron transport in biological systems. The S-nitrosation reaction and its reverse reaction represent the most convenient general way to store, to transport and finally to release NO. Nitric oxide is also particularly convenient for playing a role in interconversions of thiol groups and disulfides in chain radical or oxidation-reduction processes, and to be subsequently engaged in complex sequences of reactions accounting for different biological situations. PMID- 8462680 TI - Metabolic channelling and control of the flux. AB - Metabolic control theory is extended to include channelled metabolism in general. A simple relationship between the flux control by the enzymes and the degree of metabolite channelling is derived. This relationship suggests experiments in which modulation of gene expression allows one to quantify channelling. PMID- 8462681 TI - 'Channelled' pathways can be more sensitive to specific regulatory signals. AB - In 'simple' metabolic pathways the response to an external signal is readily described in terms of the effect of the signal on its receptor enzyme and the control exerted by that enzyme. We show here that in the response of 'channelled' pathways to such a signal, additional terms appear that reflect the direct enzyme enzyme interactions. They tend to enhance the responsiveness of the pathway. The normalized value of the response is called the signal transduction coefficient. We show that in channelled pathways these coefficients are usually larger than in corresponding non-channelled (simple) pathways. PMID- 8462682 TI - Distribution of non-class-III beta-tubulin isoforms in neuronal and non-neuronal cells. AB - beta-Tubulin isoforms in brain tissues and in cell lines were analyzed by high resolution isoelectric focusing in combination with monoclonal antibodies. Post translational modifications of brain non-class-III beta-tubulin isoforms were found in phylogenetically distant species ranging from pig to carp. Less extensive modifications were also observed in Neuro-2a, HeLa and 3T3 cells, where most acidic isoforms were glutamylated, while the basic, most abundant isoforms were not. The data suggest post-translational modification of non-class-III beta tubulin isoforms in neuronal as well as in non-neuronal cells. Such modification might modulate interaction of tubulin with microtubule-associated proteins. PMID- 8462683 TI - Tyr-571 is involved in the T7 RNA polymerase binding to its promoter. AB - The in vitro studies of three T7 RNA polymerase point mutants suggest that substitutions of Ala and Thr for Pro-563 and of Ser for Tyr-571 have little effect on the enzyme catalytic competence, but result in its inability to utilize the promoter. Both P563A and P563T mutants retain the promoter-binding ability, whereas the promoter affinity of the Y571S mutant drops drastically. PMID- 8462684 TI - The IP3-sensitive calcium store of HIT cells is located in a surface-derived vesicle fraction. AB - Electron microscopic and biochemical techniques were used to study the cellular localization of the ATP-dependent, IP3-sensitive, Ca2+ store in the glucose- and phosphatidylinositol(PI) agonist-sensitive hamster insulinoma cell line HIT-T15. Scanning electron microscopy revealed conspicuous shape changes of the microvilli following stimulation of these cells with bombesin or thapsigargin. These changes closely resemble those previously shown to accompany stimulation of hexose transport in adipocytes with insulin [J. Cell. Physiol. 142 (1990) 1-14]. Using a hydrodynamic shearing technique for the isolation of microvilli, two cell surface derived vesicle fractions were prepared containing 80% of the total cellular Ca(2+)-storing activity. In contrast, subcellular fractionation using normal homogenization with a glass/teflon homogenizer yielded the well-known distribution of the Ca(2+)-storing activity which is then predominantly recovered within the microsomal fraction. The surface-derived vesicle fraction was clearly distinguished from the microsomal fraction by its high content of Na+/K(+)-ATPase and an immunoreactive fragment of the GluT-1 glucose transporter isoform which both are not detectable in the microsomal fraction isolated from homogenates from sheared cells. The Ca2+ uptake properties of the cell surface-derived vesicle fractions including the vanadate, A23187, and thapsigargin sensitivity were found to be identical with those described for the microsomal Ca2+ stores of various cell types. Inositol 1,4,5-trisphosphate (IP3) at 1 microM induced a maximal release of 35-40% of the stored Ca2+ from these vesicles. PMID- 8462685 TI - Site-directed mutagenesis of yeast phosphoglycerate kinase. Arginines 65, 121 and 168. AB - In the absence of a structure of the closed form of phosphoglycerate kinase we have modified by site directed mutagenesis several of the residues which, on the basis of the open form structure, are likely to be involved in substrate binding and catalysis. Here we report on the kinetic and anion activation properties of the yeast enzyme modified at positions 65, 121 and 168. In each case an arginine, thought to be involved in the binding of the sugar substrate's non-transferable phosphate group, has been replaced by lysine (same charge) and by methionine (no charge). Km values for 3-phosphoglycerate of all six mutant enzymes are only marginally higher than that of the wild-type enzyme. Removing the charge associated with two of the three arginine residues appears to influence (as judged by the measured Km's) the binding of ATP. Although binding affinity is not necessarily coupled to turnover the substitutions which have the greatest effect on the Km's do correlate with the reduction in enzymes maximum velocity. The one exception to this generalisation is the R65K mutant which, surprisingly, has a significantly higher kcat than the wild-type enzyme. In the open form structure of the pig muscle enzyme each of the three substituted arginines residues are seen to make two hydrogen bonds to the sugar substrate's non-transferable phosphate. From this it might be expected that anion activation would be similarly affected by the substitution of any one of these three residues. Although the interpretation of such effects are complicated by the fact that one of the mutants (R65M) unfolds at low salt concentrations, this appears not to be the case. Replacing Arg121 and Arg168 with methionine reduces the anion activation whereas a lysine in either of these two positions practically destroys the effect. With the substitutions at residue 65 the opposite is observed in that the lysine mutant shows anion activation whereas the methionine mutant does not. PMID- 8462686 TI - Differential inhibition of fungal oxidosqualene cyclase by 6E and 6Z isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene. AB - Inhibitory properties of 6E (compound 1) and 6Z (compound 2) isomers of 2,3-epoxy 10-aza-10,11-dihydrosqualene against oxidosqualene-lanosterol cyclase were assayed on microsomes and whole cells of Saccharomyces cerevisiae and Candida albicans. Only the 6E isomer (compound 1), bearing a correct substrate-like configuration, strongly inhibited the enzyme both in microsomes and cell cultures. The difference between compounds 1 and 2 (which had an unfavorable geometry) was especially evident when measuring [14C]acetate incorporation into non-saponifiable lipids extracted from treated cells. While isomer Z was totally ineffective at up to 30 microM, in cells treated with 5 microM isomer E, labelled oxidosqualene, the level of which was negligible in the control, rose to over 60% of the non-saponifiable lipids. PMID- 8462687 TI - Identification of a key domain in annexin and 14-3-3 proteins that stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells. AB - Calcium-dependent secretion in digitonin-permeabilized adrenal chromaffin cells is stimulated by exogenous annexin II and 14-3-3 proteins. These proteins share a conserved domain that has been suggested to be involved in specific protein protein interactions. We examined whether this domain was involved in secretion by using a synthetic peptide (P16) of sequence KGDYQKALLYLCGGDD corresponding to the C-terminus of annexin II. P16, but not truncated peptides, prevented the stimulation of secretion by 14-3-3 proteins and produced a partial inhibition of control secretion. These data suggest that the shared annexin/14-3-3 domain is important in the mechanisms controlling Ca(2+)-dependent secretion and may play a key role in protein-protein interactions during exocytosis. PMID- 8462688 TI - Analysis of the role of the COL1 domain and its adjacent cysteine-containing sequence in the chain assembly of type IX collagen. AB - The mechanisms of chain selection and assembly of type IX collagen, a heterotrimer alpha 1(IX)alpha 2(IX)alpha 3(IX), must differ from that of fibrillar collagens since it lacks the characteristic C-propeptide of these latter molecules. We have tested the hypothesis that the information required for this process is contained within the C-terminal triple helical disulfide-bonded region (LMW). The reassociations of the purified LMW fragments of pepsinized bovine type IX collagen were followed by the formation of disulfide-bonded multimers. Our data demonstrate that only three triple helical assemblies form readily, (alpha 1)3, (alpha 2)3 and alpha 1 alpha 2 alpha 3. The information required for chain selection and assembly is thus, at least in part, contained in the studied fragments. Molecular stoichiometries different from the classical heterotrimer may thus also form under certain conditions. PMID- 8462689 TI - Positional and additive effects of basic amino acids on processing of precursor proteins within the constitutive secretory pathway. AB - We have recently shown that the Arg/Lys-X-Lys/Arg-Arg or Arg/Lys-X-X-X-Lys/Arg Arg sequence serves as a signal for cleavage of precursor proteins within the constitutive secretory pathway, and this cleavage is catalyzed by furin, a mammalian homolog of the yeast Kex2 protease. In this study, we further examined sequence requirements for the constitutive precursor cleavage. Based on the data concerning cleavage efficiencies of various prorenin mutants with amino acid substitution(s) around the native cleavage site expressed in CHO cells, we revised the sequence rules that govern the constitutive cleavage as follows: (i) the Arg residue at position -1 is essential; (ii) in addition to the Arg at position -1, at least two out of the three basic residues at positions -2, -4, and -6 are required for efficient cleavage (the presence of all the three basic residues results in most efficient cleavage); (iii) at position +1, a hydrophobic aliphatic amino acid is not suitable. PMID- 8462690 TI - Nicking of the tryptophan synthase beta 2-subunit at Glu-296 prevents the conformational change undergone on binding the alpha-subunit. AB - Using a monoclonal antibody as conformational probe it has been shown that the weakly active nicked-beta 2 dimer of tryptophan synthase generated by proteolytic cleavage at Glu-296, does not undergo on association with alpha subunit a conformational change known to occur in intact beta 2 subunit. This alpha induced conformational change is also prevented in intact beta 2 by the coenzyme pyridoxal-5'-phosphate when the substrate L-serine is absent. PMID- 8462691 TI - Isolation and characterization of a protease from the marine sponge Spheciospongia vesparia. AB - A protein that showed activity against proteic (casein and hide powder azure) and synthetic (BAEE and HLPA) substrates was isolated from the marine sponge Spheciospongia vesparia. The protease was purified from an aqueous extract by ammonium sulfate precipitation, gel filtration, hydrophobic and HPLC-anion exchange chromatographies. The purified protease showed a single band in SDS-PAGE minigels and had a molecular weight of 29,600, but when submitted to isoelectric focusing it showed 2 bands with isoelectric points of 4.56 and 4.43. Its catalytic action was inhibited by EDTA and 1,10-phenanthroline, so it seemed to be a metalloprotease. PMID- 8462692 TI - Localization of a fibrin polymerization site complementary to Gly-His-Arg sequence. AB - Dansyl-labeled tetrapeptide Gly-His-Arg-Pro which mimics the central fibrin polymerization site was used to investigate its binding to a number of fibrinogen fragments containing different numbers of domains. The tetrapeptide was found to bind to fragments DH(95 kDa), DL(82 kDa) and DY(63 kDa) but not to the TSD(28 kDa) fragment. The DY fragment differs from the TSD by the presence of beta and beta C domains. Therefore these domains, which are formed by the C-terminal part of the beta chain, possess a polymerization site complementary to the Gly-His-Arg containing counterpart. PMID- 8462693 TI - What is hemimethylated DNA? PMID- 8462695 TI - Bioluminescence of the Ca(2+)-binding photoprotein, aequorin, after histidine modification. AB - Modification studies of the 5 histidine residues in aequorin employing site directed mutagenesis and diethyl pyrocarbonate suggested that His169 may be the site of binding of molecular oxygen in aequorin. The modification of this residue led to complete loss of activity, whereas modification of the remaining 4 histidine residues yielded mutant aequorins with varying bioluminescence activities. PMID- 8462694 TI - Isolation of two members of the rat MAP kinase kinase gene family. AB - Mitogen-activated protein (MAP) kinase kinase (MAPKK) is a recently characterized activator of MAP kinase (MAPK), and is considered to be regulated by a protooncogene product c-Raf-1. It is, however, unclear whether the signals originating from c-Raf-1 utilize this phosphorylation cascade to lead to oncogenesis. To clarify this point, we isolated rat MAPKK cDNAs, and identified two distinct cDNAs encoding MAPKK and a highly related kinase, both with molecular weights of approximately 45 kDa (MEK1 and MEK2). Genomic Southern blot analyses suggested that MAPKK may form a large gene family. PMID- 8462696 TI - Two structural genes are encoding malate synthase isoenzymes in Saccharomyces cerevisiae. AB - We report on the isolation of a gene encoding yeast malate synthase. A yeast genomic library was screened using a probe homologous to the yeast enzyme obtained by the polymerase chain reaction. The nucleotide sequence of the cloned gene was determined. Computer analysis showed that the isolated gene is identical to the one previously described as DAL7, which is involved in allantoin metabolism [Mol. Cel. Biol. 9 (1989) 3231-3243]. Enzymatic activities of multicopy transformants, Southern analysis and disruption mutants predict the existence of two genes encoding malate synthases that are differentially regulated at the transcriptional level. PMID- 8462697 TI - Restoration of dystrophin-associated proteins in skeletal muscle of mdx mice transgenic for dystrophin gene. AB - Duchenne muscular dystrophy (DMD) patients and mdx mice are characterized by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoproteins, including dystroglycan which provides a linkage to the extracellular matrix component, laminin. The finding that all of the dystrophin-associated proteins (DAPs) are drastically reduced in DMD and mdx skeletal muscle supports the primary function of dystrophin as an anchor of the sarcolemmal glycoprotein complex to the subsarcolemmal cytoskeleton. These findings indicate that the efficacy of dystrophin gene therapy will depend not only on replacing dystrophin but also on restoring all of the DAPs in the sarcolemma. Here we have investigated the status of the DAPs in the skeletal muscle of mdx mice transgenic for the dystrophin gene. Our results demonstrate that transfer of dystrophin gene restores all of the DAPs together with dystrophin, suggesting that dystrophin gene therapy should be effective in restoring the entire dystrophin-glycoprotein complex. PMID- 8462698 TI - Varicose veins and the vascular surgeon: from nuisance to challenge. PMID- 8462699 TI - A method to transluminally seed angioplasty sites with endothelial cells using a double balloon catheter. AB - Acute arterial reocclusion and late restenosis following angioplasty may be partially caused by loss of the endothelial cell monolayer during balloon dilatation. Rapid restoration of the endothelial cell monolayer by endothelial cell transplantation has the potential to increase the antithrombotic nature of the angioplasty site and also to prevent myointimal hyperplasia which is the cause of late restenosis. We have investigated a method to transluminally deliver endothelial cells to angioplasty sites using a double balloon catheter with a central instillation port. Inflation of the balloons allows a segment of artery to be isolated from the circulation which may then be incubated with infused endothelial cells. The external iliac arteries of New Zealand white rabbits were dilated for 30 s at 8 atm pressure using a 3 mm balloon angioplasty catheter. Indium-111 labelled allogeneic rabbit endothelial cells were seeded onto the angioplasty site and retained in contact with the vascular surface for 30 min by continued inflation of the isolation balloons. After 30 min, the balloons were deflated and flow restored. Percentage cell retention was calculated by determining the gamma activity of the seeded angioplasty site, and referencing this to the contralateral sham seeded site. Results are expressed as a median with 95% confidence intervals and suggest that endothelial cells may be successfully delivered and retained on damaged vascular surfaces [table: see text]. PMID- 8462700 TI - Postoperative graft incorporation after aortic reconstruction--comparison between computerised tomography and Tc-99m-HMPAO labelled leucocyte imaging. AB - Aortic graft infection may result in high mortality ranging up to 88%. Therefore, early diagnosis is imperative in the treatment of this serious complication. Computerised tomography (CT) is considered as a sensitive tool in the diagnosis of aortic graft infection. Some findings used as the criteria for infection, such as periprosthetic gas and fluid are, however, normal postoperative findings. The aim of this prospective study was to compare CT-scan and Tc-99m-HMPAO labelled leucocytes in the early diagnosis of aortic graft infection. The present study includes 24 consecutive patients (all men, age 70 +/- 8 years, range 55-85 years), who were operated on for abdominal aortic aneurysm. Prosthetic and suture materials were the same in all operations. Each patient was examined with the aid of CT-scan and imaged with Tc-99m-HMPAO labelled leucocytes 2 weeks and 3, 6 and 12 months after the reconstructive aortic surgery. Two radiologists and two specialists in nuclear medicine examined the data independently without knowing the clinical picture of the results of any other examinations of the patients. Seven patients (7/24; 29%) showed significant accumulation of labelled leucocytes in the first imaging (2 weeks postoperatively) with Tc-99m-HMPAO labelled leucocytes. Three months after the surgery only four patients (4/24; 17%) were positive in this respect. One of these patients had clinically proven aortic graft infection and another positive was a patient with resected and reconstructed mycotic aneurysm. CT-examination in all scans was suggestive for aortic graft infection in two cases (2/24; 8%), but neither of these patients showed any signs of infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462701 TI - Cellular biology of human intimal hyperplastic stenosis. AB - Restenosis after angioplasty and vascular surgery remains a major unsolved clinical problem. Vascular smooth muscle cell (VSMC) hyperplasia is an invariable response, but in 20-50% of cases proceeds to compromise the vessel lumen. We sought to identify cellular characteristics of human VSMC which are associated with restenosis. Human VSMC were grown from 135 samples of vascular tissue derived from patients undergoing primary cardiovascular surgery and revision surgery for restenosis. Cells derived from normal vein and artery, atherosclerotic plaques and from stenotic lesions were studied for successful proliferation in cell culture. Furthermore, growth rates were measured in response to 15% foetal calf serum +/- inhibition with heparin (100 micrograms/ml). Significantly fewer cells from atherosclerotic plaques progress to the third passage in cell culture than those derived from stenoses and controls (p < 0.001, Chi square) and growth rates after the third passage could not be studied in these cells. Of cells that progress to this stage, growth rates do not differ between stenosis-derived and normal cells under standard conditions. VSMC from mature atherosclerotic plaques may have undergone senescent changes. Stenosis-derived cells do not grow more rapidly than normal cells, but are significantly less sensitive to heparin (p < 0.001, Mann-Witney test), which is a major physiological inhibitor of VSMC growth. Differences in biological characteristics of human VSMC, observed in cell culture, may provide important insights into human vascular disease. PMID- 8462702 TI - Management of asymptomatic popliteal aneurysms: the use of a Markov decision tree to determine the criteria for a conservative approach. AB - With recent improvements in the results of treatment of popliteal aneurysms, it has been suggested that it may be preferable to treat asymptomatic aneurysms conservatively and to operate only if symptoms develop. This hypothesis has been tested using decision analysis, with sensitivity and threshold analysis to establish the conditions under which such a policy would be appropriate. A Markov decision tree has been used to model the problem and the relevant probabilities have been obtained from a review of the current literature. A computer spreadsheet was used to calculate the results of policies of immediate operation or operation only if symptoms occur. Sensitivity and threshold analysis have been carried out to assess the effect of inaccuracy or alteration in the key variables and to determine the optimum policy under different conditions. The results suggest that early elective operation produces better results than conservative management at 1-2 years after presentation. Sensitivity analysis reveals that the most crucial data are the rate of development of symptoms in patients with asymptomatic aneurysms and the expected limb loss and mortality of treatment for symptomatic aneurysms. Threshold analysis has been used to define the values of these parameters that would be necessary for conservative management to be preferred. It is concluded that, based upon the currently available data, the optimum policy is elective treatment of asymptomatic aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462703 TI - Cardiac risk stratification using dipyridamole myocardial perfusion imaging and ambulatory ECG monitoring prior to vascular surgery. AB - Both dipyridamole myocardial perfusion imaging (cardiolite) and ambulatory ECG monitoring (Holter) for silent ischaemia have been found to be useful for stratification of cardiac risk in patients undergoing vascular surgery. The purpose of this study was to compare the diagnostic accuracy of these two non invasive tests for prediction of perioperative cardiac events. One hundred patients (86 males, 14 females; mean age 67 +/- 8 years) underwent out-patient 48 h Holter monitoring and cardiolite imaging prior to vascular surgery (70 abdominal aortic aneurysm, 21 aortobifemoral, nine femoralpopliteal grafts). Ischaemia on Holter was defined as one or more episodes of ST segment depression 1 mm or greater, lasting 1 min or longer. Myocardial perfusion imaging was carried out with the high dose dipyridamole protocol (0.84 mg/kg), cardiolite and planar imaging. Ischaemia was defined as a segmental perfusion abnormality following dipyridamole with improved perfusion on rest imaging. Holter was positive for ischaemia in 34/100 patients (34%). Cardiolite scans were positive for ischaemia in 30/100 patients (30%). Perioperative myocardial infarction occurred in nine patients (two cardiac deaths). [table: see text] The diagnostic accuracy of the two tests was similar, with a low positive predictive value of 15 20%, and an extremely high negative predictive value of 94-96%. The event rate in patients with both tests negative was 2/48 (4.2%), with only one test positive 3/40 (7.5%) and with both tests positive 4/12 (33%). A reasonable approach to risk stratification would be to obtain either a Holter or cardiolite scan initially.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462704 TI - The integrity of experimental vein graft endothelium--implications on the etiology of early graft failure. AB - INTRODUCTION: the vascular endothelium serves as a functional barrier between the circulating blood and the vessel wall. It is an essential element for the maintenance of vascular homeostasis and is implicated in the pathogenesis of vascular disease. Reversed vein bypass grafting is considered to be a devastating procedure for the endothelial cell layer of the graft during the first 7 days. At this time, smooth muscle cell proliferation, the forerunner of intimal hyperplasia, begins. Loss of endothelial cell integrity is cited as an important factor in this smooth muscle cell response. The integrity of the vein graft endothelial lining after grafting was examined in this study. METHODS: reversed vein bypass grafting of the common carotid artery using external jugular vein was performed in 24 New Zealand white rabbits. All grafts were pressure fixed (80 mmHg) in situ, at 0 and 10 min, 6 h and 1, 3, 5, 7 and 14 days postoperatively. The endothelial cell layer was examined by light microscopy (LM), scanning (SEM) and transmission electron microscopy (TEM) and immunohistochemistry (Factor VIII) using standard histological procedures. RESULTS: the endothelium was observed by SEM and confirmed by both LM, Factor VIII and TEM in all specimens. It covered almost the entire surface examined. At 0 and 10 min, endothelial cells were present and displayed minimal evidence of injury. At 6 h and 1 day, numerous red cells, polymorphonucleocytes (PMNs), platelets and fibrin were adherent to the luminal surface. Blood cells were also seen beneath the endothelium. At day 3, the adherent fibrin and cellular elements were reduced with most of the endothelial lining intact. Within 10 min, TEM demonstrated that these cells were stretched, very thin with few microvesicles and a blurred cytoplasm, which would indicate viability but a degree of cellular injury. By day 1, the endothelial cells were lifted from their underlying structures by subendothelial oedema and an infiltrate predominantly of PMNs. By day 5, the blood cells and fibrin which were adherent to the endothelium had been dispersed and the subendothelial infiltrate was to a large extent replaced by disintegrated PMNs. On days 7 and 14, a viable confluent endothelial cell layer was present and a degree of intimal hyperplasia was noted. The endothelial cells appeared to have enlarged nucleoli and cytoplasms filled with a considerable quantity of rough endoplasmic reticulum. CONCLUSION: the endothelium of reversed vein grafts is preserved at the time of implantation and at all time intervals studied in this model. These findings do not support the assumption that endothelial denudation is a prerequisite for intimal hyperplasia. Endothelial cell dysfunction and morphological changes are maximal within the first 3 days after grafting but appear to recover by the 5th postoperative day. The gross preservation of the endothelial cell layer implies that therapeutic approaches, to mitigate endothelial cell injury and its consequences, should be focused on the preoperative period and the first 5 days following implantation. PMID- 8462705 TI - Natural history of patients with unoperated atherosclerotic carotid artery disease--results from a retrospective study. AB - The natural history of carotid artery disease was studied in a retrospective study of 609 angiograms performed during 1969-1979 on patients who had subsequently not been operated on. The indication for angiography differed, but was aimed at clarifying suspected cerebrovascular events. 578 patients could be followed-up after a median time of 10.4 years (0-22). The median survival time after angiography was 9.7 years for the 355 men and 12.8 years for the 223 women (p = 0.0099). Internal carotid stenosis of > 50% was seen in 9.0% (bilaterally in 2.2%), a stenosis > 75% in 4.5% (bilaterally in 0.9%) and occlusion in 9% (bilaterally in 0.7%). Ulceration was present in 10.7% (bilaterally in 1.6%). 26.5% of the patients had a cerebrovascular event during follow-up, of which 31.4% had transient ischaemic attack or amaurosis fugax. Survival was not influenced by the degree of stenosis, but presence of arteriosclerotic carotid artery disease significantly reduced the median survival time from 11 to 3 years. The main cause of death for men was myocardial infarction (27.7%) and for women a cerebrovascular event (27.8%), a significant difference. From this study, in selected patients it can be concluded that the annual frequency of cerebrovascular events was low, approaching frequencies reported in asymptomatic patients. The cause of death differed between men and women, with more cardiac deaths among men and more cerebrovascular deaths among women. PMID- 8462706 TI - Three dimensional time-of-flight magnetic resonance angiography in carotid artery surgery: a comparison with digital subtraction angiography. AB - Three dimensional time-of-flight magnetic resonance angiography (MRA) and intra arterial digital subtraction angiography (DSA), considered the gold-standard technique, were compared for pre- and postoperative evaluation of the carotid bifurcation. Images of suitable quality of 194 bifurcations were available with both techniques. Percentage stenosis was graded into 5 groups: A = 0-29%, B = 30 59%, C = 60-89%, D = 90-99%, E = 100% (occlusion). Preoperative MRA (126 bifurcations) overgraded the stenosis in 14 cases and undergraded it in 11. The two techniques agreed in 101 cases and the extent of misgrading was never more than one category. Regression analysis showed a good correlation between the two methods. Severe ulceration was better identified by DSA. As far as the surgical indication was concerned, MRA had a sensitivity of 92.6% and a specificity of 98.3%. In 68 operated cases, postoperative MRA and intraoperative completion angiography showed a satisfactory endarterectomy with no residual stenosis in any of the cases. In conclusion, MRA seems an accurate modality for imaging of carotid bifurcations. Significant limitations still exist for an adequate demonstration of intracranial circulation. PMID- 8462707 TI - Calf vessel preservation in peripheral vascular disease--angiography versus pulse generated run-off. AB - Previous angiographic and radiological studies have suggested that the peroneal artery is the best preserved of the calf vessels in peripheral vascular disease and should be a site of preference for a femorodistal bypass graft. Calf vessel run-off assessed by pulse generated run-off (PGR) provides a more accurate prediction of graft success or failure than angiography and may therefore give a better functional picture of vessel patency than angiography. This study compares the presence and degree of preservation of the three calf vessels in patients with severe peripheral vascular disease using both intra-arterial digital subtraction angiography (IADSA) and PGR. Thirty-four limbs in patients with either ischaemic rest pain, ulceration or gangrene were studied and the results were scored according to the extent and severity of disease in the peroneal, posterior tibial and anterior tibial arteries. On IADSA, the peroneal artery was patent significantly more often (79%) than the posterior tibial artery (47%) or the anterior tibial artery (38%). Conversely, PGR examination showed no difference in patency between the three vessels (peroneal 91%, posterior tibial 88%, anterior tibial 79%). The peroneal artery was also significantly better preserved on IADSA (65%) compared to the posterior tibial artery (38%) and the anterior tibial artery (23%). PGR studies again showed no difference in the best preserved vessel between peroneal (47%), posterior tibial (50%) and anterior tibial (50%) arteries. Thus, the peroneal artery appears the better preserved vessel on angiography but this appearance may be misleading because the more functional PGR studies show no significant difference in the patency or degree of preservation of the three calf vessels. PMID- 8462708 TI - Cardiac risk screening of peripheral arterial surgical patients by the use of combined simple clinical and non-invasive cardiodynamic parameters. AB - Arterial surgical patients have a poor long-term survival and suffer significant risks of experiencing perioperative cardiac events, mainly due to a high incidence of coronary atherosclerosis impairing left ventricular function. The perioperative cardiac risk can be assessed by use of clinical cardiac risk indices, which are inexpensive but may have suboptimal sensitivity, or by more extensive cardiac tests. In this study the efficacy of a combined, non-invasive and inexpensive technique of risk assessment was prospectively evaluated in 195 patients undergoing peripheral arterial surgery (aortic aneurysms not included). All patients were preoperatively examined by a nurse registering the Detsky cardiac risk index score (DRI) and performing resting computerised bioimpedance cardiodynamic measurements (CM). Cardiac deaths (CD, n = 6), potentially lethal cardiac complications (PLC, n = 11) within 30 days and long-term survival during 20 +/- 12 (S.D.) months of follow-up were identified. CD was best predicted by combining CM and DRI, while PLC was best predicted by combining DRI and the haemoglobin concentration of the blood (Hb). A group without CD containing 88% of the cases was identified. Furthermore, the combination of DRI < or = 10 and Hb > 120 g/l identified a low risk group (57% of all cases) with no PLC or CD. Using CM, DRI and Hb in combination, patient groups with long-term survival from 0-90% were identified. We conclude that this inexpensive cardiac risk screening both identifies low risk vascular surgical patients, for whom more sophisticated preoperative cardiac testing can be omitted, and predicts long-term survival. PMID- 8462709 TI - Renal duplex scanning: correlation with angiography and isotopic renography. AB - The purpose of this study was to assess the accuracy of Duplex scanning in detecting renovascular disease and to compare it with angiography, renal scintigraphy and captopril test for plasma renin activity and isotopic renography. A Duplex scan was performed in 92 renal arteries (46 patients) and compared to angiography. Three degrees of stenoses were established: 0-60%, 61 99% and occlusion. The peak systolic velocity (PSV) in the renal artery and its ratio to the peak velocity in the aorta (RAR) were used to discriminate stenoses > 60%. PSV in the interlobar arteries was used to assess the relative perfusion of both parenchyma. Angiography demonstrated a stenoses > 60% in 23 hypertensive patients. In all of the patients, plasma renin activity was measured and isotopic renograms (pre- and post-captopril) obtained in order to discriminate hypertension of vascular origin. A PSV in the renal artery > 210 cm/s and a RAR > 3.5 were found to be the diagnostic criteria with the best sensitivity and specificity in detecting stenoses > 60%. Based on these data, Duplex correctly identified 49/54 stenoses > 60%; 28/33 stenoses < 60%; and 5/5 occlusions (kappa 0.79). Sensitivity and specificity in detecting stenoses > 60% were 89.5 and 90.7%, respectively. The ratio between PSV in the interlobar arteries of both parenchyma accurately predicted the relative perfusion (ratio between DTPA uptake in both kidneys) in the isotopic test (n = 23, r = 0.91, p = 0.001). The captopril test (for plasma renin activity and isotopic renography) was positive in only five patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462710 TI - Peripheral nerve function in chronic venous insufficiency. AB - Abnormalities of vasomotion, impairment of the venoarteriolar reflex and increased skin blood flow reported in the liposclerotic skin of patients with chronic venous insufficiency (CVI) suggest altered nervous control of the skin microcirculation. The aim of this study was to determine whether patients with CVI have a peripheral neuropathy. Forty patients with CVI and lipodermatosclerosis (LDS) and 35 age and sex-matched controls were examined for neuropathy using three modalities of testing. Threshold to warming was used to assess unmyelinated fibres, and threshold to cooling and vibration to assess myelinated fibres. Warming and cooling thresholds were measured on the sole of the foot by a purpose built, computer controlled instrument. The threshold to vibration was measured on the big toe using the Ohio Bio-thesiometer. A significantly raised threshold to warming and vibration was found in the CVI group compared to the normal controls [median threshold to warming (interquartile range) in CVI group = 5.3 (0.1-9.1) median threshold to warming (interquartile range) in controls = 1.21 (0.17-3.5), p = 0.005 and median threshold to vibration (interquartile range) in CVI group = 22 (13-31) median threshold to vibration (interquartile range) in controls = 12 (8.5-27.5), p = 0.024]. The thresholds to cooling was not statistically different in the two groups. This study demonstrates the presence of a peripheral neuropathy in patients with chronic venous insufficiency, and this may be important in the pathogenesis of venous ulceration. PMID- 8462711 TI - Congenital absence of inferior vena cava. PMID- 8462712 TI - Chylous ascites: a rare complication following aortic surgery. PMID- 8462713 TI - Two vascular complications of the Ehlers-Danlos syndrome. AB - Patients with Ehlers-Danlos syndrome type IV have thin walled, friable arteries and veins and are prone to spontaneous arterial rupture. We present a patient who suffered severe damage to the common femoral vein during surgery for varicose veins and who subsequently suffered a spontaneous rupture of the right external carotid artery, treated by ligation and oversewing. Intraarterial radiology and surgery in such patients are hazardous and should be avoided if possible. Where operation is essential, the simplest available procedure should be performed. Patients should be counselled to inform every doctor they consult that they have the Ehlers-Danlos syndrome. PMID- 8462714 TI - False aortic aneurysm presenting as sciatic nerve root pain. AB - Neurological symptoms and signs are rarely the only presenting feature of abdominal aortic aneurysm. We present a patient presenting with sciatic nerve root pain due to a large false aneurysm in iliopsoas. PMID- 8462715 TI - Autumnal aneurysm ruptures. PMID- 8462716 TI - Femoropopliteal arterial reconstruction. PMID- 8462717 TI - Second European Consensus Document on Chronic Critical Limb Ichaemia. PMID- 8462718 TI - Why, when and how does the poly(A) tail shorten during mRNA translation? AB - 1. The length of the poly(A) tail at the 3'-end of mRNA may control protein synthesis by bringing the 3'-end in close proximity to the 5'-end of the noncoding region as well as increasing the duration of mRNA translation by its binding to the poly(A) binding protein. 2. The rate-limiting step in the decay of the body of the message is the shortening of a long poly(A) tail during mRNA translation. The shortening of the poly(A) tail occurs during pre-elongation in the protein synthesis cycle. 3. The shortening of the poly(A) tail during mRNA translation may not involve RNase activity, however poly(A) binding protein seems to play a role, at least in part, in shortening of the poly(A) tail. PMID- 8462719 TI - Control of glycolytic enzymes through binding to cell structures and by glucose 1,6-bisphosphate under different conditions. The role of Ca2+ and calmodulin. PMID- 8462720 TI - Protein engineering on subtilisin. PMID- 8462721 TI - Occurrence of a 29 kDa polysaccharide in the slime layer of both smooth and rough strains of Pseudomonas aeruginosa. AB - 1. The lipopolysaccharide (LPS) and the extracellular products (slime) of a smooth, nonmucoid Pseudomonas aeruginosa strain (PAC IR) and its rough mutant (PAC 605) were subjected to a comparative biochemical analysis. 2. Chemical and electrophoretic analyses suggested that the slime preparation of both strains are composed mainly of similar carbohydrate components which are different from those of the respective lipopolysaccharides. 3. Chromatographic analysis of the two slime preparations on gel permeation HPLC columns revealed the presence of a major polysaccharide in both strains with an apparent molecular weight 29 kDa and a minor high molecular weight polysaccharide in the PAC IR strain. PMID- 8462722 TI - The inhibitory effect of tetramethylethylene diamine on water soluble and membrane bound acetylcholinesterase activity. AB - 1. The inhibitory effect of N,N,N',N'-tetramethylethylene diamine (TEMED) on water soluble (WSAChE) and membrane bound (MBAChE) acetylcholinesterase was investigated. 2. TEMED (0.5-4.0 mM) reversibly inhibited WSAChE activity (18-62%) and MBAChE (20-61%) in a concentration dependent manner. 3. The IC50 being about 2.8 mM for WSAChE and 2.6 mM for MBAChE. 4. Lineweaver-Burk plots indicated that the nature of inhibition is noncompetitive for both water soluble and membrane bound acetylcholinesterase, with Km values 68 microM and 123 microM respectively. 5. An Arrhenius plot showed that the transition temperature (TT) is unaffected in the presence of TEMED. 6. The activation energy was increased below and above TT in the case of WSAChE only. 7. On the basis of this behaviour of TEMED with AChE, it can be proposed that it can be used as an eluting agent for the bounded AChE to affinity ligand and may have beneficial action on the reactivatability of irreversibly-inhibited AChE due to its structure. 8. Moreover there is a possibility that it can be used as a therapeutic agent for the treatment of Alzheimer's disease, myasthenia gravia and glaucoma like some other inhibitors of AChE. PMID- 8462723 TI - Hyaluronidase degradation of hyaluronic acid from different sources: influence of the hydrolysis conditions on the production and the relative proportions of tetra and hexasaccharide produced. AB - 1. Hyaluronic acid (HA) can be digested with a Streptomyces hyaluronidase. 2. The rate of production and the ratio of tetrasaccharide (T) and hexasaccharide (H), studied by HPLC, varied with the temperature and duration of hydrolysis. 3. The rates of production and the respective amounts of the two oligosaccharides depended on the rheological properties of the HA from different sources. 4. A close relationship was found between the initial rate of hydrolysis and the intrinsic viscosity of the HA (eta i). 5. Our data suggest that enzymatic degradation at a given pH value, temperature, and duration of hydrolysis is dependent on the conformation of HA. 6. Moreover, under given conditions, the relative proportions of the two oligosaccharides depend on the eta i and may also reflect the degree of hydrolysis of the substrate. PMID- 8462724 TI - Monoclonal antibodies prepared against heparin lyase I and their reactivity toward heparin lyase I, II and III. AB - 1. Six different monoclonal IgG mouse antibodies to heparin lyase I from Flavobacterium heparinum were prepared. 2. The monoclonal antibodies were used to detect heparin lyases I, II and III by dot-blotting immunoassay and by Western blotting. 3. Individual antibodies showed different reactivity toward the three heparin lyases. 4. The reactivity of two of the monoclonal antibodies was destroyed by exposing heparin lyases to sodium dodecyl sulfate. 5. The antibodies can be used to rapidly distinguish between the three heparin lyases. PMID- 8462725 TI - Effects of exercise training and anabolic steroids on plantaris and soleus phospholipids: a 31P nuclear magnetic resonance study. AB - 1. The purpose of this study was to examine the effect of exercise, anabolic steroid treatment, and a combination of both treatments on the phospholipid composition of predominantly fast twitch (plantaris) and slow twitch (soleus) skeletal muscles. The 4 experimental groups analyzed were sedentary control (C), steroid-treated (S), exercise-trained (E), and exercise plus steroid-treated (ES). 2. Among the 11 phospholipids quantitated, for the plantaris muscle, phosphatidylcholine was reduced in ES relative to C, while phosphatidylethanolamine and phosphatidylethanolamine plasmalogen were elevated in E and ES relative to C. For the soleus muscle, phosphatidylserine was reduced in S and E relative to C, and cardiolipin was elevated in E relative to C. 3. Of the 27 metabolic indices calculated for the plantaris, 15 changed significantly among E and ES relative to S and C, while for the soleus, only three indices changed among the four groups, two among E and ES relative to S and C and one between S and C. 4. For the plantaris muscle, the results are consistent with an exercise-induced alteration of membrane phospholipid composition that increases ion translocation activity. For the soleus muscle, this membrane alteration essentially does not take place. 5. Steroid treatment had little to no statistically significant effect on plantaris and soleus muscle phospholipid systems, regardless of the imposed regimen. PMID- 8462726 TI - Inactivation of ornithine decarboxylase by intermediates of tyrosinase-catalyzed reaction. AB - 1. Intermediates in the process of melanin synthesis formed through oxidation of catechols by tyrosinase produced the inactivation of ornithine decarboxylase (ODC), a key enzyme in the polyamine biosynthesis pathway. 2. The inactivation was dependent on the substrate used (dihydroxybenzylamine > L-3,4 dihydroxyphenylalanine > L-tyrosine) and on the concentration of intermediate produced rather than on the rate of formation. 3. Sulfhydryl compounds (dithiothreitol and glutathione) or quinone-reducing agents (ascorbic acid) prevented the inactivation of ODC; L-ornithine, but not other amino acids, also protected partially ODC. The results suggest that different cysteine residues in ODC molecule are implicated in the inactivatory event. 4. When 14C-labeled catechols were used, numerous polypeptides resulted labeled, showing that the reactive quinones formed as intermediates in the process of melanin biosynthesis bind covalently to many cellular proteins. PMID- 8462727 TI - Expression of a putative catalytic domain of the human APEX nuclease (a major apurinic/apyrimidinic endonuclease) in Escherichia coli. AB - 1. Sequence analyses of APEX nuclease, a mammalian major apurinic/apyrimidinic (AP) endonuclease homologous to Escherichia coli exonuclease III, suggested that APEX nuclease is organized into two domains, a Mr 6000 N-terminal domain containing nuclear location signals and a Mr 29,000 C-terminal catalytic domain. 2. In order to study the enzyme structure further, vectors expressing APEX nuclease (pTAPXH1) and the Mr 29,000 C-terminal region (pTAPXH61) were constructed using cDNA (APX cDNA) for the human APEX nuclease and pTrc99A plasmid. The constructs were introduced into BW2001 strain (xth-11, nfo-2) cells of E. coli to produce transformants designated as BW2001/pTAPXH1 and BW2001/pTAPXH61, respectively. Both the APEX nuclease expressed in BW2001/pTAPXH1 and the Mr 29,000 C-terminal peptide expressed in BW2001/pTAPXH61 were partially purified by column chromatography and highly purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. 3. The purified APEX nuclease and the Mr 29,000 C-terminal peptide both showed equally high AP endonuclease activity which indicates that the Mr 29,000 C-terminal region of the APEX nuclease is (or contains) the AP endonuclease domain. PMID- 8462728 TI - Measurement of non-enzymic glycosylation with a radiochemical assay. AB - 1. A radiochemical assay has been developed to measure non-enzymic glycosylation (glycation), which is free from interference from enzymic glycosylation and which can be used in batch analysis. 2. Glycated residues were isolated by affinity chromatography on mini-columns, after reduction with Na[3H]BH4 and hydrolysis. 3. The specific activity of the labelled borohydride was measured by a novel procedure. 4. The method was used to measure glycation of albumin, immunoglobulin G and fibrinogen isolated from diabetic and non-diabetic subjects. PMID- 8462729 TI - Lipoxygenase and other enzymes of arachidonic acid metabolism in the brain of chicks affected by nutritional encephalomalacia. AB - 1. Prostaglandin endoperoxide synthetase (PES) and lipoxygenase (Lox) activities were compared in the cerebella and cerebra of vitamin E-sufficient young chicks and in chicks in which nutritional encephalomalacia (NE) was induced by a diet deficient in vitamin E. 2. Eicosanoid production patterns were qualitatively similar in the brains of both groups of chicks, but prostaglandin production was 50-60% less in cerebella of ataxic chicks, compared to control cerebella, while the opposite trend was observed in the cerebellar Lox pathway, as measured by radioimmunoassay of 15-HETE. 3. Cerebellar phospholipase A2 activity was twice that of the cerebrum but was not affected by NE. 4. Purification of Lox activity from the cerebellar homogenates produced a lower yield and enrichment when the starting material was taken from ataxic chicks, compared to the controls. 5. In addition there were qualitative differences in the purified fractions from both groups, as seen by pH optima and kinetics. 6. The results are consistent with the view that the cerebellum has less antioxidant protection than the cerebrum and that its higher phospholipase A2 activity and greater propensity to oxygenate arachidonic acid via the Lox pathway at the expense of the PES pathway may render this region of the brain particularly vulnerable to oxidative damage in NE. PMID- 8462730 TI - Comparative analysis of the antibodies against capsular polysaccharides of Escherichia coli K-92 and K-235: an immunochemical method for the identification of polysialic acids. AB - 1. The antibodies produced against the capsular poly-N-acetylneuraminic acid (poly-Neu5Ac) of E. coli K-92 (alpha 2-8-, alpha 2-9-linked) were 100-fold less sensitive than those obtained against E. coli K-235 capsular polysaccharide (CP) (alpha 2-8-linked) and recognized both kinds of polymers to a similar extent. 2. The partial hydrolysis of each purified polysaccharide revealed that E. coli K-92 CP is more labile at acidic pH than the polymer alpha 2-8-linked of E. coli K 235. 3. The antisera against CP from E. coli K-92 bound its own oligomers in which the number of Neu5Ac units was higher than three, whereas they only cross reacted with the oligomers derived from E. coli K-235 containing a number of residues higher than 12. 4. The antisera against E. coli K-235 CP that recognized alpha 2-8 oligomers with a number of Neu5Ac residues higher than 5, also reacted, although very weakly, with those containing alpha 2-8 and alpha 2-9 linkages in which the carbon length was higher than (Neu5Ac)3. 5. Both types of antibodies were also able to recognize the native antigens in living bacteria and could be employed for the recognition of the type of linkage presents in different sialylpolymers. PMID- 8462731 TI - Selective effect of melatonin on the proliferation of lymphoid cells. AB - 1. The present study was designed to investigate the effect of melatonin on the proliferation of normal lymphocytes and certain T-lymphomas and myelomas under in vitro conditions. 2. The results revealed that administration of 200 microM melatonin inhibited significantly the incorporation of [3H]thymidine into both normal mouse and human lymphocytes and T-lymphoblastoid cell lines. 3. On the contrary, melatonin provoked an increase of myeloma cell proliferation. 4. The influence of melatonin on hybridoma cell lines was negligible. 5. Collectively, these data demonstrated that the chief pineal indole affect selectively the processes of lymphoblastoid cell growth. PMID- 8462732 TI - The phospholipase activities present in preheparin mouse plasma are inhibited by antiserum to hepatic lipase. AB - 1. Preheparin plasma from mice, but not rats or man, contains high levels of phospholipase A and lysophospholipase activities which are distinct from lecithin:cholesterol acyltransferase (LCAT). 2. Neither the phospholipase A nor the lysophospholipase activities in preheparin plasma are inhibited by incubation in the presence of protamine sulphate or high salt concentrations. 3. When mouse plasma is incubated in the presence of an antiserum specific for rat hepatic triacylglycerol lipase (HTGL), the phospholipase activities are abolished. 4. These observations suggest that the phospholipase activities are attributable to the action of HTGL, which, in the mouse appears to be a freely circulating enzyme, whereas for other species this enzyme only appears in the blood following administration of heparin. PMID- 8462733 TI - Proliferation of chicken myoblasts is regulated by specific isoforms of platelet derived growth factor: evidence for differences between myoblasts from mid and late stages of embryogenesis. AB - In the present study we measured the level of PDGF receptor expression by chicken myoblasts and the effect of the three different PDGF isoforms (AA, AB, BB) on DNA synthesis by myoblasts. We examined PDGF receptor expression and function on clonally derived myoblasts in order to eliminate contaminating fibroblasts which are present in myogenic cultures and which bind PDGF. Furthermore, since we have previously shown that fetal myoblasts are replaced with adult myoblasts during late chicken embryogenesis, we compared PDGF receptor expression and function on myoblasts from Embryonic Day 10 (E10, mid development) and from Embryonic Day 19 (E19, late development). We found that all myogenic clones from late embryos (E19) express many receptors for PDGF-BB, far fewer receptors for PDGF-AB, and even fewer, if any, receptors for PDGF-AA. Myoblast clones derived from E10 were more heterogeneous in their PDGF binding pattern ranging from clones similar to E19 clones to clones having very few PDGF binding sites. We also found that both PDGF-AB and PDGF-BB can promote DNA synthesis by clonally derived chicken myoblasts maintained in 2.5% fetal bovine serum whereas PDGF-AA has no detectable effect. Finally, we observed that primary myogenic cultures from E10 and E19 differ strikingly in levels of PDGF binding; E19 cultures bind much more PDGF than do E10 cultures. We conclude that PDGF can enhance the proliferation of chicken myoblasts and that myoblasts responsive to PDGF are more frequent in late than in mid stages of development. We propose that PDGF may be a modulator of myogenesis of adult but not fetal myoblasts. PMID- 8462734 TI - Expression of the SmN splicing protein is developmentally regulated in the rodent brain but not in the rodent heart. AB - The SmN protein is a tissue-specific splicing factor which is closely related to the ubiquitous SmB splicing protein but which is expressed only in the adult brain and heart. SmN is also detectable albeit at a low level in both the embryonic brain and heart. During heart development, SmN levels remain constant while during rodent brain development the levels of SmN rise such that SmN replaces SmB as the predominant protein in adult brain. This increase in SmN levels is dependent upon a corresponding increase in the SmN mRNA which is detectable by in situ hybridization within neurons in virtually all areas of the adult brain. PMID- 8462735 TI - A functional role for the middle extracellular region of the neural cell adhesion molecule (NCAM) in axonal fasciculation and orientation. AB - A new monoclonal antibody (mAb HR1) was used to study the function of a previously neglected region in the extracellular domain of the neural cell adhesion molecule (NCAM). Application of mAb HR1 in retina organ culture interferes with several axonal functions in the developing eye. The antibody disturbs the orientation of axons growing in the peripheral retina and the tracking of axons in the middle retina. In the central retina, fasciculation is disturbed and a proportion of the ganglion cell axons do not leave the eye at the optic fissure but are misrouted to the contralateral side of the retina. Analysis of peptide fragments of NCAM indicates that the epitope of mAb HR1 resides in the region C-terminal to the fifth immunoglobulin (Ig) domain. Moreover, mAb HR1 binds to the oligopeptide comprising the 15 amino acids immediately C-terminal to the fifth Ig domain of NCAM. In addition, binding of mAb HR1 to NCAM is increased by removal of the large polysialic acid chains of the fifth Ig domain. Taken together, the data show that this region of NCAM--which has been previously reported to represent the flexible hinge region of the molecule--is crucial for the function of this molecule, in particular on cell surfaces in motion, e.g., those of growing axons in the developing nervous system. PMID- 8462736 TI - Neural crest-derived cells isolated from the gut by immunoselection develop neuronal and glial phenotypes when cultured on laminin. AB - The neural crest-derived cells that colonize the bowel are different from their predecessors in the premigratory crest. A procedure, which utilized the immunoselection of cells with a magnet, was thus devised to obtain crest-derived precursors from developing gut. Primary antibodies against cell surface antigens, NC-1 in chick, quail, and rat, or antibodies to a 110-kDa laminin binding protein (alpha-110) in mouse, were used in conjunction with secondary antibodies coupled to magnetic beads. Immediately after immunoselection with NC-1, almost all of the selected cells were NC-1-immunoreactive. Neurons and glia, identified immunocytochemically with antibodies to specific markers, developed preferentially in cultures of immunoselected cells. Some of the phenotypes expressed by neurons arising in vitro were appropriate for the bowel (serotonin- and vasoactive intestinal peptide-immunoreactive); however, catecholaminergic neurons, which are not present in the enteric nervous system, also differentiated in the cultures. Neuronal development, as well as neurite outgrowth, were promoted by laminin. Cells selected with alpha-110 from the fetal murine bowel preferentially gave rise in vitro to neurons and glia. These data suggest that the population of crest-derived cells that colonizes the gut is multipotent, that development of catecholaminergic neurons in situ is prevented by the intact enteric microenvironment, that laminin is important in the formation of enteric ganglia, and that the 110-kDa laminin binding protein is expressed on the surfaces of the immediate precursors of enteric neurons and glia. PMID- 8462737 TI - Characterization of the mineralization process in cultures of rabbit growth plate chondrocytes. AB - The present study was undertaken to investigate the mineralization process in chondrocyte cultures. Chondrocytes were isolated from the growth plate of ribs of 4-week-old rabbits. The nature and properties of mineral crystals precipitated in chondrocyte cultures were compared with those of crystals formed in the hypertrophic zone and bone of rabbit rib growth plates in vivo. The chondrocytes were maintained at high density on type II collagen-coated dishes in Eagle's medium, alpha-modification, with 10% fetal bovine serum and 50 micrograms/ml of ascorbic acid. These cells differentiated into hypertrophic cells 10 days after seeding and produced alkaline phosphatase and 1,25-dihydroxyvitamin D3 receptors on Days 30-70 at levels as high as those in the lower hypertrophic zone in vivo. Mineralization was initiated between Days 20 and 30 and advanced progressively throughout the culture period. However, mineralization was suppressed by the addition of parathyroid hormone (2 x 10(-8) M) or by the presence of fibroblasts. Examination by electron microscopy and Fourier transform infrared (FTIR) spectroscopy verified that mineralized nodules formed in vitro were composed of small apatite crystals. Importantly, FTIR spectral features of the apatite crystals (e.g., the prominent PO4 bands at 1125 and 1032 cm-1) were similar to those of cartilage apatites formed in vivo and differed markedly from those of carbonated bone apatites. These results suggest that growth plate chondrocytes cultured on collagen-coated dishes are an appropriate model for studies on cartilage mineralization. PMID- 8462738 TI - Transient appearance and localization of a 26-kDa lectin, a novel member of the Periplaneta lectin family, in regenerating cockroach leg. AB - A lectin consisting of a 26-kDa subunit was purified from the hemolymph of adult American cockroaches (Periplaneta americana) and shown to be a member of the Periplaneta lectin family. Immunoblotting analysis revealed that this lectin appeared transiently in regenerating legs after nymphal legs were amputated. Thus, its mode of appearance was similar to that of regenectin, another member of the Periplaneta lectin family. However, its time of appearance and localization in the regenerates were different from those of regenectin: the 26-kDa lectin appeared in regenerates in the middle stage of regeneration and was localized in the vicinity of the outside of newly formed epidermal cells. These results suggest that this lectin participates in the organization or stabilization of the epidermis during leg regeneration. PMID- 8462739 TI - Mosaic methylation in clonal tissue. AB - Current models suggest that de novo methylases add methyl groups to mammalian DNA early in development, establishing cell-specific patterns of methylation, and that these patterns are maintained by maintenance methylases that copy them onto newly replicated DNA strands. To test the prediction that clonal populations of histologically homogeneous cells should, therefore, have homogeneous methylation patterns, we studied methylation in leiomyomas. Despite the clonality and histological homogeneity of these solid tumors, we found that cells were heterogeneously methylated at a number of genomic sites. The heterogeneity was not caused by random methylation events within the leiomyomas because methylation patterns were similar in the core and periphery of a given tumor, and similar also among samples of independent leiomyomas and surrounding myometrial tissues extracted from a single uterus. Our results also showed that methylation of a site in the YNZ22 locus--in leiomyomas and in smooth muscle--was determined independently from the methylation of a neighboring site. Similar results were obtained for the IGH locus in colon and in several tumor tissues. These data indicate that methylation patterns are not identical in progeny cells, as current models suggest. Instead, it seems likely that methylation of a specific site reflects an equilibrium frequency defined by a continual loss and gain of methyl groups. Hence, the specificity found for the methylation of mammalian tissues is not achieved by strictly determining the methylation fate of individual cells, but by determining the overall methylation frequencies for individual sites. PMID- 8462740 TI - Identification of DNA-binding protein(s) in the developing heart. AB - An antiserum (anti-H2) directed at the second helix of the helix-loop-helix (HLH) protein MyoD1 reacts with a protein expressed during avian cardiac myocyte differentiation. Indirect immunohistochemical whole mount staining with anti-H2 detected a protein expressed in stage 11 hearts, but not in hearts of older embryos. At the cellular level, this staining is confined to the nucleus of cardiac cells suggesting that these proteins may have DNA-binding abilities. Several proteins were immunoprecipitated by anti-H2 from stage 11 heart tissue. Protein extracts from similarly staged hearts, when incubated with the muscle specific enhancer sequence of muscle creatinine kinase (MCK), gave a stage specific band shift in electromobility shift assays (EMSA), and these protein-DNA complexes were recognized and supershifted by anti-H2. Incubation with a MCK sequence containing a mutated E box did not produce a shift. The specific shift was present as early as stage 6, remained through stage 13, and disappeared by stage 17. These data suggest the presence of at least one protein that is transiently expressed in the differentiating cardiac myocyte, that is immunochemically reactive with an antiserum raised against the second helix of MyoD1, and that binds to a muscle-specific DNA enhancer sequence. PMID- 8462741 TI - Expression of AV-1, a position-specific molecule, in response to retinoic acid beads and ZPA grafts in chick limb development. AB - Local application of retinoic acid (RA) to the anterior-distal margin of chick limb buds causes digit pattern duplications identical to those that result from zone of polarizing activity (ZPA) grafts. The AV-1 antigen is a cell membrane glycoprotein which is expressed during chick limb bud development in a stage- and position-specific manner that correlates with cartilage pattern formation. In order to further understand the limb patterning mechanisms affected by RA and by ZPA grafts, we first examined the effects of RA treatment on AV-1 expression. We then compared the effect of RA with those of ZPA grafts. When beads soaked in varying concentrations of RA were applied to the anterior-distal margin of wing buds, changes in the pattern of AV-1 antigen expression were observed. AV-1 expression appears to correlate with regions that will give rise to a digit 3. These results suggest that the AV-1 protein is one of the molecules which may be involved in the process of cartilage pattern formation during limb development. ZPA grafts produced similar alterations in AV-1 expression, but the initial changes were observed earlier with ZPA grafts than with RA beads. These results support the idea that RA changes anterior limb bud cells into ZPA cells. PMID- 8462742 TI - Transcriptional elements from the human SP-C gene direct expression in the primordial respiratory epithelium of transgenic mice. AB - Transgenic animals bearing a chimeric gene containing 5'-flanking regions of the human surfactant protein C (SP-C) gene ligated to the bacterial chloramphenicol acetyltransferase (CAT) gene were analyzed by in situ hybridization histochemistry to determine the temporal and spatial distribution of transgene expression during organogenesis of the murine lung. Ontogenic expression of the SP-C-CAT gene was compared to that of the endogenous SP-C gene and to the Clara cell CC10 gene. High levels of SP-C-CAT expression were observed as early as Day 10 of gestation in epithelial cells of the primordial lung buds. Low levels of endogenous SP-C mRNA were detected a day later, but only in the more distal epithelial cells of the newly formed, primitive, lobar bronchi. On Gestational Days 13 through 16, transcripts for both the endogenous and chimeric gene were restricted to distal epithelial elements of the branching bronchial tubules and were no longer detected in the more proximal regions of the bronchial tree. Although high levels of SP-C-CAT expression were maintained throughout organogenesis, endogenous SP-C expression increased dramatically on Gestational Day 15, coincident with acinar tubule differentiation at the lung periphery. Low levels of endogenous CC10 expression were detected by Gestational Day 16 in both lobar and segmental bronchi. By the time of birth, CC10 transcripts were expressed at high levels in the trachea and at all levels of the bronchial tree; endogenous SP-C mRNA was restricted to epithelial cells of the terminal alveolar saccules; and SP-C-CAT expression was now detected in both alveolar and bronchiolar epithelial cells. These results indicate that (1) cis-acting regulatory elements of the human SP-C gene can direct high levels of foreign gene expression to epithelial cells of the embryonic mouse lung; (2) expression of the human SP-C-CAT chimeric gene is developmentally regulated, exhibiting a morphogenic expression pattern similar, but not identical, to that of the endogenous murine SP-C gene; (3) the embryonic expression of endogenous SP-C and chimeric SP-C-CAT transcripts identifies progenitor cells of the distal respiratory epithelium; and (4) differentiation of bronchial epithelium is coincident with loss of SP-C expression and subsequent acquisition of CC10 expression in proximal regions of the developing bronchial tubules. PMID- 8462743 TI - Fibroblast growth factor influences the development and cycling of murine hair follicles. AB - The effects of basic fibroblast growth factor (bFGF) on the development of hair follicles in neonatal mouse skin were examined. Newborn mice (B6C3-based strain) were given daily subcutaneous injections of bFGF and bovine serum albumin (BSA) for 7 days. By Day 9, distinct areas of hairless, unpigmented skin were observed surrounding the sites treated with bFGF. This phenomenon persisted until about 14 16 days of age when the emergence of hair in the bald patches was first seen. Hair growth continued in the treated regions until they were mostly covered at 18 20 days of postnatal age. Control sites injected with BSA only were indistinguishable from the surrounding pigmented, hairy skin at all ages. Histological examination of skin from various ages of bFGF-treated mice suggested that the growth factor had affected both the initiation and the development of the hair follicles. This resulted in a significant delay in the first and subsequent hair cycles when compared to control animals injected with BSA only. PMID- 8462744 TI - Growth cones respond in diverse ways upon encountering neurites in cultures of chick dorsal root ganglia. AB - To help in understanding the role that interactions with other axons may have in helping to guide sensory neuron growth cones along the appropriate pathways in the chick hindlimb, we have examined how sensory growth cones respond when they contact the processes of other sensory neurons. Videotaping of neurons in dissociated cell cultures, as they participated in such encounters, showed that sensory growth cones can demonstrate any one of a number of responses: crossing, fasciculation, parallel growth, or retraction. We observed a variety of responses even among neurons from a single segment, suggesting the possibility that this is due to a heterogeneity of cell-surface labels among the neurons present within an individual dorsal root ganglion. If sensory neurons behave in vivo as we found they do in culture, the diverse behaviors of sensory growth cones may contribute to the process by which different subsets of axons sort out into separate, discrete bundles as they extend into the periphery during development. The diversity of responses we observed stands in contrast to the results of Kapfhammer, J.P., and Raper, J.A., [(1987) J. Neurosci. 7, 1595-1600] who found that sensory growth cones always cross sensory neurites. Possible explanations for the differences in the results were explored and are discussed. PMID- 8462745 TI - Cell sorting within the prespore zone of Dictyostelium discoideum. AB - Dictyostelium discoideum forms elongate cell aggregates called "slugs" which migrate over the substrate before completing their conversion into fruiting bodies. Prespore cells are found in a zone which occupies the rear four-fifths of the slug. Both front- and rear-prespore cells, marked by a bacterial beta galactosidase gene, sort out to their original positions in experiments in which slugs are reconstituted from disaggregated tissue. When cells from the rear of the prespore zone are transplanted to the middle or front, sorting is also observed: the transplanted cells return rapidly to the rear. Cells from the front of the prespore zone, however, were not observed to "home" to the front after transplantation to the rear. Since front-prespore cells sort out in disaggregation/reaggregation experiments, but fail to do so after transplantation to the rear, it is possible that the transplanted cells are converted to rear prespore cells by extracellular signals present in the rear of the slug. In an experiment designed to test this hypothesis, front cells were transplanted to the rear and the host and transplant together then subjected to disaggregation/reaggregation. The results showed that front-prespore cells had not been converted to rear-prespore cells. Instead, there was an unanticipated effect: cells placed in the rear of the prespore zone underwent an anterior shift in positional preference, while cells placed in the front of the prespore zone showed a posterior shift. The specific sorting properties of front- and rear prespore cells thus do not appear to result from the action of positional signals; positional signals destabilize rather than reinforce sorting preferences. Our observations are consistent with a model in which innate differences among cells bias them to differentiate as front-prespore or rear prespore types, but the proportions of these types are also modulated by a negative-feedback mechanism. PMID- 8462746 TI - Effects of the mesonephros and insulin-like growth factor I on chondrogenesis of limb explants. AB - The mesonephros has been shown to have a growth-promoting influence in vivo on limb outgrowth. This influence has been studied in detail using an organ culture system. The results show that in the presence of the mesonephros limb explants formed larger cartilages than cultures without mesonephros. Furthermore, with mesonephros, morphology of the cartilages is comparable to that of skeletal elements in vivo while cartilages formed in cultures lacking mesonephros were amorphous. The mesonephric influence also promoted the formation of a well organized extracellular matrix in the cartilage while cartilage in cultures without mesonephros formed an abnormal appearing matrix. Cartilage matrices in cultures with or without mesonephros were immunoreactive to type IX and type II collagens, cartilage proteoglycan PGH, and link protein although cultures lacking mesonephros had a very restricted distribution of type IX collagen immunoreactivity. Despite the different distribution of type IX collagen, long form-type IX collagen transcripts appeared similar in both types of culture based on in situ hybridization. The mesonephric effect on limb explants could be partially duplicated by the addition of insulin-like growth factor I (IGF-I) to cultures without mesonephros. Furthermore, the mesonephric influence on cartilage growth and morphological differentiation could be blocked by the addition of a blocking antibody to IGF-I to cultures with mesonephros. The results support the hypothesis that IGF-I is one of the growth factors produced by the mesonephros which may play a role in early limb development and chondrogenesis. PMID- 8462747 TI - Formation of myotubes in aneural rat muscles. AB - Skeletal muscles formed in the absence of innervation are deficient in number of fibers, atrophic, and prone to degeneration. We and others have suggested that primary myotubes form autonomously, and the major effect of embryonic denervation is to halt the formation of secondary myotubes by removing the mitotic stimulus for generation of their precursor myoblasts. This hypothesis has recently been put into question by the results of work by Condon et al. (Dev. Biol., 138, 275 295, 1990) and by B. J. Fredette and L. T. Landmesser (Dev. Biol. 143, 19-35, 1991) who propose that lowered secondary myotube numbers are at least in part due to absence of the primary myotubes which would normally serve as scaffold for their formation. We distinguish between these hypotheses by studying generation and degeneration of primary myotubes and formation of secondary myotubes in fetal rat muscles denervated by injection of beta-bungarotoxin at different times between Embryonic Days (E) 14 and 17. Denervation at any of these times reduced primary myotube numbers on E18 to about 80% of control. Despite this modest decrease in primary myotube numbers, secondary myotube generation fell to below 3% of normal in extensor digitorum longus (EDL) muscles denervated on E14 or E15 and to below 12% of control in soleus muscles denervated on E14-E16. Secondary myotubes were associated with degenerating as well as intact primary myotubes. More secondary myotubes were generated only if nerves had been present up until E16 for EDL or E17 for soleus. We suggest that these observations of a critical period until E16 (EDL) or E17 (soleus) during which innervation is an absolute prerequisite for secondary myotube formation reflect the presence of a nerve dependent population of myoblasts which must be activated before secondary myotube formation can commence. PMID- 8462748 TI - Formation of primary and secondary myotubes in aneural muscles in the mouse mutant peroneal muscular atrophy. AB - The role of motor innervation in supporting and regulating muscle development was studied using aneural muscles in the hindlimb of the mouse mutant peroneal muscular atrophy (pma). This is a single-locus autosomal mutation where homozygous animals lack the common peroneal nerve, so that muscles in the anterolateral compartment of the lower leg develop entirely without innervation. In adults, these muscles are extremely atrophied, and the mice display a clubfoot deformity. The mutant animals provide a preparation in which aspects of muscle formation can be studied in muscles that have never been exposed to direct contact with somatic motor or sensory axons, without pharmacological or surgical intervention. Using quantitative electron microscopy, we found that normal numbers of primary myotubes formed in aneural pma EDL muscles, but a greater than normal proportion degenerated during the first 2 days after their formation. Secondary myotubes appeared at their normal time and position within the muscle, initially in normal numbers, so that the ratio of secondary to primary myotubes initially was greater in pma than in CF1 control strain mice. No abnormalities in ultrastructure were seen until the time of birth, when retardation in development was obvious, together with invading macrophages and degenerating myofibres. The results show that secondary myotube formation in the mouse, as in the chick (B. J. Fredette and L. T. Landmesser, Dev. Biol. 143, 19-35, 1991) is not directly dependent on innervation. In control muscles, secondary myotubes first form in the vicinity of endplates on primary myotubes. No aggregations of ACh receptors or acetylcholinesterase were present in the aneural muscles, showing that these are neurally induced in the mouse, but secondary myotubes formed in their normal position indicating that positional information related to endplate formation is present in aneural muscles. PMID- 8462749 TI - Regulation of myogenesis in paralyzed muscles in the mouse mutants peroneal muscular atrophy and muscular dysgenesis. AB - The roles of innervation, muscle electrical activity, and muscle contraction in regulating the formation and survival of primary and secondary myotubes during embryonic and fetal development of skeletal muscle were studied using the mouse mutants peroneal muscular atrophy (pma) and muscular dysgenesis (mdg). The pma phenotype includes the absence of the peroneal division of the sciatic nerve, so muscles in the anterior compartment of the lower hindlimb are aneural throughout development. Muscles in mdg mice are paralyzed due to the absence of excitation contraction coupling and hyperinnervated due to suppression of motoneuron death in consequence of their paralysis, but otherwise are electrically excitable and receive synaptic transmission. In a quantitative comparison between control and mutant extensor digitorum longus (EDL) muscles at E15, primary myotube numbers were depressed by 20-30% in both mutants and in paralyzed or denervated muscles from control strain animals. The number of secondary myotubes, however, was normal in pma mutants and two and a half times greater than normal in the hyperinnervated mdg EDL muscles, so that the ratio of secondary to primary myotubes was increased by 300% in the mutant with respect to heterozygous or -/- littermates. Chronic paralysis with tetrodotoxin (TTX) caused no further depression of primary myotube numbers in aneural pma muscles, but secondary myotube numbers were reduced by 40%, reducing the ratio of secondary to primary myotubes by 35%. We conclude that during normal development the generation of secondary myotubes depends on neurally evoked electrical activity in primary myotubes, which stimulates mitosis of secondary myoblasts. The effect of TTX shows that aneural pma primary myotubes discharge spontaneous myogenic action potentials, while mdg muscles may receive greater than normal electrical activation due to their hyperinnervation, explaining the presence and numbers of secondary myotubes in the mutant mouse muscles. PMID- 8462750 TI - Reporter gene expression in G2 of the 1-cell mouse embryo. AB - Similar amounts of expression of a luciferase reporter gene that is driven by the SV40 early promoter are detected in G2 of 1-cell mouse embryo following injection of the male pronucleus in either early or mid/late S. No luciferase activity is observed when the male pronucleus is injected in early S and the embryos analyzed for expression in late S. Last, no luciferase activity is observed when the female pronucleus is injected in mid/late S and the embryos analyzed for luciferase activity in G2 of the first cell cycle. These results suggest that zygotic gene activation initiates in the 1-cell embryo rather than in the 2-cell embryo, as previously thought, and that differences between the transcriptional activity of male and female pronuclei exist. PMID- 8462751 TI - Developmental control elements in the promoter of a Drosophila vitelline membrane gene. AB - DNA fragments from the 5' flanking region of Drosophila melanogaster vitelline membrane gene VM26A1 were fused to hsp/lacZ reporter genes, reintroduced via P element-mediated germ line transformation, and functionally assayed by histological staining for beta-galactosidase activity. A developmental control element capable of promoting the basic vitelline membrane (VM) expression pattern was found within a 176-bp region. Additional multiple genetic control elements were found to be involved in modifying the level and spatial pattern of reporter gene expression but these required the 176-bp element in order to function. Unexpectedly, in isolation this 176-bp core element also promotes abnormal expression of the reporter gene in border cells of stage 8 and 9 egg chambers. This abnormal border cell expression is apparently suppressed in the native gene by an adjacent negative control element. PMID- 8462752 TI - Structural changes of the endoplasmic reticulum of sea urchin eggs during fertilization. AB - The endoplasmic reticulum (ER) of the sea urchin egg includes a system of cisternae, a cortical tubular network, and the nuclear envelope. In previous work (Terasaki and Jaffe, 1991, J. Cell. Biol. 114, 929-940) we showed that the long chain fluorescent lipophilic dye DiI spread from an intracellularly injected oil drop into all of these parts of the ER. In this previous study, we observed that in the first minute after fertilization, the ER cisternae became more finely partitioned; the large cisternae then reformed by 5-8 min after fertilization. To investigate whether these changes indicated a breaking up of the ER into discontinuous pieces, we have now examined the ability of DiI to spread in the ER at various times after fertilization. In eggs injected after fixation with aldehydes, we find that DiI spreads through the ER in unfertilized eggs and in eggs at 10 min postinsemination. However, DiI does not spread out of the oil drop in eggs fixed at 1 min postinsemination. We also find that in live eggs, the spreading of DiI is slower in eggs at 1-3 min postinsemination than in unfertilized eggs or in eggs later after fertilization. We interpret these observations to indicate that in the first few minutes after fertilization, the egg's ER is fragmented. This may be functionally significant for the early events of egg activation. PMID- 8462753 TI - Treatment is not enough. PMID- 8462754 TI - Spastic quadriplegia in Western Australia. II: Pedigrees and family patterns of birthweight and gestational age. AB - Pedigrees were obtained for all 74 index children and for three controls for each case. Recurrence of similar spastic quadriplegic phenotypes occurred in two families. A karyotype of 46,XY,dup(13)(q14q34), resulting in a partial trisomy 13, was found in another case. Rates of miscarriages and stillbirths plus neonatal deaths were higher among siblings of index cases than in siblings of birth-year controls, but were similar to siblings of birthweight controls. Average birthweights and gestational ages were lower in index cases than in birth year controls. Children with spastic quadriplegia had significantly lower birthweights and gestational ages than their siblings. However, they also tended to come from families with a pattern of low birthweight and preterm delivery. The differences between families remained after controlling for factors affecting birthweight. PMID- 8462755 TI - Effects of upper-extremity weight-bearing on hand-opening and prehension patterns in children with cerebral palsy. AB - The purpose of this study was to determine whether upper-extremity weight-bearing has an effect on hand-opening and prehension patterns of children with spastic cerebral palsy. Children at the Bobath Centre (London) were studied. Effectiveness of intervention was determined by blind scoring of video-tapes of prehension components. Computer calculations of hand surface-area were done. There was an over-all increase in surface area, indicating an increased ability to open the hand; in addition, there was an increase in the maturity of movement components of prehension. These results provide relevant information about the application of upper-extremity weight-bearing. PMID- 8462756 TI - Auditory event-related potentials and reaction time in children: evaluation of cognitive development. AB - The authors studied age-related correlations of auditory event-related potentials (ERPs) using the conventional 'oddball' paradigm and reaction time in 175 normal subjects, aged between four and 21 years. From four years, the latencies of N100, N200 and P300 in ERP progressively shortened until about 16 to 17 years, after which they reached adult level, but with a slight tendency to prolongation towards 20 years; there was no trend for amplitude changes. The reaction time was more rapid than that of P300 latency. These findings indicate that the cognitive function of children improves rapidly until 16 to 17 years. A reduced difference between P300 latency and reaction time with age implies additional progress in motor skill. Combining P300 latency and reaction-time studies may provide more detailed information for the evaluation of the development of cognitive function and motor skill. PMID- 8462757 TI - Clinical epidemiology of childhood abdominal migraine in an urban general practice. AB - The present study examined the epidemiology of abdominal migraine among 1104 children registered with a general practice. There was a similar prevalence of recurrent abdominal pain as in other studies (8.4 per cent). The prevalence of headache was higher among children with recurrent abdominal pain and significantly so among girls. Migrainous headache was not significantly more prevalent in children with recurrent abdominal pain. The prevalence of abdominal migraine with and without migrainous headache was 0.7 and 1.7 per cent, respectively. The peak prevalence of abdominal migraine without migrainous headache was between five and seven years for both sexes. When associated with migrainous headache, it peaked at five to seven years in girls and seven to nine years in boys. The syndrome was associated with travel sickness and was more common among girls and those with a maternal history of migraine. Many children were photo- and phonophobic during an attack. PMID- 8462758 TI - Neurological findings in newborn infants after extracorporeal membrane oxygenation, with special reference to the EEG. AB - Seventeen newborn infants were treated with extracorporeal membrane oxygenation (ECMO). Two died shortly after the start of ECMO due to the underlying disease, two died later in the course due to a lack of recovery of lung function and two others died weeks after ECMO from renal damage and a cardiac defect. Of the survivors, nine are developing normally (aged between one and four years) and two are severely disabled because of infarctions of the left hemisphere, acquired before and after ECMO. Intermittent-discontinuous EEGs did not indicate a poor prognosis if normalization of the EEG occurred within seven days. However, infarcted areas on ultrasonography, persistent EEG changes or deteriorating findings indicated disability or early death. PMID- 8462759 TI - Idiopathic lumbosacral plexus neuropathy in two children. AB - Two children diagnosed as having idiopathic lumbosacral plexopathy are presented. Although an apparently rare condition, it is probably underdiagnosed since it is difficult to recognise. Before such a diagnosis, careful exclusion of compressive and infiltrative lesions of the spinal cord, cauda equina and lumbosacral plexus is of utmost importance. PMID- 8462760 TI - Hemodynamic instability of myelomeningocele patients during anterior spinal surgery. AB - Surgery for spinal fusion for patients with myelomeningocele is accompanied by a high rate of complications. The authors report six cases of sudden intra operative hemodynamic instability which occurred during anterior spinal fusion; the procedures had to be aborted. All children were successfully resuscitated and four patients subsequently underwent successful anterior and posterior spinal fusion. Four of the children had positive skin and serum allergy tests to latex. PMID- 8462761 TI - Seizure exacerbation related to beta-lactam antibiotics in a child with cerebral dysgenesis. AB - A three-year-old boy with right hemimegalencephaly, developmental delay and left hemiparesis had well-controlled left focal seizures. Occasionally he had generalized seizures if he was given beta-lactam antibiotics. An EEG with simultaneous penicillin injection was performed to examine this apparent association: a secondarily generalized seizure was documented within two minutes of intravenous administration of the penicillin. This procedure confirmed the suspicion of a causal link between antibiotic treatment and seizures. The factors increasing susceptibility to beta-lactam antibiotic-induced seizures are reviewed. PMID- 8462762 TI - Does computed tomography have a role in the evaluation of complicated acute bacterial meningitis in childhood? PMID- 8462763 TI - Seizures and intellectual disability associated with tuberous sclerosis. PMID- 8462764 TI - 'Status epilepticus. I: Pathogenesis'. PMID- 8462765 TI - Islet amyloid polypeptide in the rabbit and European hare: studies on its relationship to amyloidogenesis. AB - In this study, we determined the cDNA-predicted amino acid sequence of positions 9-31 of islet amyloid polypeptide from the rabbit and European hare. A synthetic rabbit/hare islet amyloid polypeptide 20-29 peptide was subsequently shown to be strongly fibrillogenic in vitro even though the putative amyloidogenic AILS sequence at positions 25-28 of human and cat islet amyloid polypeptide is modified in the rabbit and hare by a substitution of phenylalanine for leucine at position 27 (i.e. AIFS). Although islet amyloid polypeptide of both the rabbit and hare has an amyloidogenic sequence and is in fact amyloidogenic in vitro, the apparent lack of in vivo islet amyloidosis in rabbits and hares may be related to relatively low levels of islet amyloid polypeptide production by the islet beta cells in these species. This was supported by our findings that there is no substantial immunoreactivity in either rabbit or hare islets, and no measurable amount either in extracts of rabbit pancreases, or in rabbit plasma. This study supports the need for at least two prerequisites for the development of islet amyloidosis in vivo: an inherent fibrillogenic sequence within the islet amyloid polypeptide molecule and an adequate local concentration of islet amyloid polypeptide to promote self aggregation and formation of islet amyloid. PMID- 8462766 TI - The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. AB - The structural counterpart of the increased glomerular filtration found in acute diabetes mellitus and experimental diabetes has been ascribed to the increased glomerular filtration surface. Using modern design-based stereological methods and light microscopy on perfusion-fixed rat kidneys the average total surface area of capillaries per glomerulus in control rats was 291 +/- 42 10(-3) mm2 (+/- SD) increasing to 383 +/- 55 10(-3) mm2 in 10-day-diabetic rats. There was a further increase to 469 +/- 70 10(-3) mm2 in 50-day-diabetic rats. The average total length of capillaries per glomerulus increased from 12.5 +/- 2.2 mm in the control rats to 16.9 +/- 2.4 mm in the 10-day-diabetic rats whereas the further increase to 19.4 +/- 3.0 mm in the 50-day-diabetic rats failed to reach statistical significance. The average number of topologically defined capillaries per glomerulus increased from 215 +/- 29 in the control rats to 260 +/- 45 and 316 +/- 29 in the 10-day-diabetic and 50-day-diabetic rats, respectively. The results showed just a slight increase in the mean length of a capillary from 58.1 +/- 6.2 microns in the control rats to 65.6 +/- 2.6 microns in the 10-day diabetic rats after which it normalized in the 50-day-diabetic rats to 61.3 +/- 3.6 microns. The geometric factor or "resistance" in Poiseuille's law did not differ between the three groups, neither did the diameter of the capillaries, nor the number of glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462767 TI - Insulin resistance and mechanical dysfunction in hearts of Wistar rats with streptozotocin-induced non-insulin-dependent diabetes mellitus. AB - The present study correlates the insulin resistance seen in the myocardium of rats with streptozotocin-induced non-insulin-dependent diabetes mellitus with insulin secretory defects, hyperglycaemia and disease duration. Two-day-old male Wistar rats were given a bolus injection of streptozotocin (0.09 mg/g body weight) which caused glucose intolerance when these animals reached adulthood. Although these rats developed a progressive resistance to the actions of insulin in the heart this did not correlate with the development of glucose intolerance. However, a correlation was seen with a shift in insulin secretory response from hyper- to hypo-secretion which developed between 6 and 14 months of age. Moreover, this shift in secretory pattern can be associated with the onset of a cardiac mechanical malfunction. PMID- 8462768 TI - Adipose tissue glycogen synthase activation by in vivo insulin in spontaneously insulin-resistant and type 2 (non-insulin-dependent) diabetic rhesus monkeys. AB - In skeletal muscle, a defect in the covalent activation of glycogen synthase by insulin has been identified in insulin resistance and in Type 2 (non-insulin dependent) diabetes mellitus, but a similar defect in insulin action at the adipose tissue has not been demonstrated. We sought to determine whether this defect in insulin action in muscle was also present in the same pathway in adipose tissue. We examined the effect of in vivo insulin on adipose tissue glycogen synthase and phosphorylase activity in normal (n = 11), hyperinsulinaemic (n = 8), and impaired glucose tolerant and Type 2 diabetic (n = 8) rhesus monkeys. Adipose tissue samples were obtained before and during a euglycaemic hyperinsulinaemic clamp. Glycogen synthase fractional velocity, independent and total activities were significantly higher in the insulin stimulated samples compared to the basal samples in the normal group (p < 0.05, respectively). In the hyperinsulinaemic group, however, insulin had no effect on glycogen synthase fractional velocity or independent activity, but did increase the total activity of glycogen synthase and phosphorylase (p < 0.05, respectively). Furthermore, both the basal and the insulin-stimulated total activities of these two enzymes were significantly greater in the hyperinsulinaemic group as compared to both the normal and the diabetic groups (p < 0.05, respectively). In the diabetic group, insulin was without effect on glycogen synthase fractional velocity, independent activity or total activity. We conclude that the covalent activation of adipose tissue glycogen synthase by insulin is absent in both obese hyperinsulinaemic and in spontaneously diabetic monkeys. PMID- 8462769 TI - Long-term effectiveness of oral vanadyl sulphate in streptozotocin-diabetic rats. AB - Recent studies have demonstrated the insulin-like effects of oral vanadyl sulphate in the streptozotocin-diabetic rat, including the amelioration of hyperglycaemia and the prevention of diabetes-related cardiac and adipose tissue dysfunction. However, the possibility that vanadyl treatment, routinely initiated at 3 days after the induction of diabetes, had prevented the full cytotoxic destruction of the beta cell, and thus accounted for the apparent anti-diabetic properties of vanadyl was questioned. Hence in the present study, we examined the effectiveness of vanadyl sulphate as a glucose-lowering and anti-diabetic agent when administration was delayed from the time of induction of diabetes. Male Wistar rats were injected with a single intravenous dose of streptozotocin (55 mg/kg). Vanadyl sulphate was administered in the drinking water at a concentration of 0.75 mg/ml from 3, 10 and 17 days after the streptozotocin injection and treatment was then maintained for 5 months. Vanadyl intake was accompanied by lowered serum levels of triglyceride and cholesterol with no associated enhancement in circulating insulin. Vanadyl-treated diabetic animals showed improved glucose tolerance while insulin release in vivo was still markedly lower than in non-diabetic rats. Adipose tissue function, as expressed by basal and epinephrine-stimulated lipolysis in isolated adipose tissue, was also normalized in vanadyl-treated diabetic animals. These responses were all observed whether vanadyl treatment was initiated 3, 10 or 17 days after induction of diabetes. Finally, prolonged treatment with vanadyl sulphate (in this case up to 5 months) did not cause any apparent hepatic toxicity as assessed histologically. Diabetes-induced morphological changes in the kidney were also prevented by vanadyl treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462770 TI - Fetal growth and impaired glucose tolerance in men and women. AB - A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p < 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p < 0.004), as did 2-h plasma insulin concentrations (p < 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition. PMID- 8462771 TI - Gender differences in a type 2 (non-insulin-dependent) diabetic population with respect to apolipoprotein E phenotype frequencies. AB - Apolipoprotein E polymorphism was examined in an Italian population of Type 2 (non-insulin-dependent) diabetic patients. There were significant differences (p < 0.05) in allele frequencies between male and female patients due to an under representation of the E4 allele in the female group. No differences in allele frequencies were noted when non-diabetic male and female control subjects were compared. Both control groups exhibited similar allele distributions to that of male diabetic patients, but were significantly different (p < 0.05) from female diabetic patients. A closer examination of the female diabetic population revealed that under-representation of the E4 allele was principally confined to patients aged 60 years or older. This subgroup showed a significantly different (p < 0.05) allele frequency profile from control subjects (both men and women) and diabetic men, whereas this was not observed in the younger diabetic women (< or = 59 years). The results are consistent with the suggestion that the E4 allele may be a particular risk factor for female diabetic patients. PMID- 8462772 TI - HLA-associated susceptibility to type 2 (non-insulin-dependent) diabetes mellitus: the Wadena City Health Study. AB - Epidemiologic data suggest that a parental history of Type 2 (non-insulin dependent) diabetes mellitus increases the risk of Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 and Type 2 diabetes. We have previously reported evidence that HLA-DR4-linked factors may represent a homogeneous subset of diabetes susceptibility. First, HLA-DR4 frequency was higher in Type 1 diabetic study subjects with a Type 2 diabetic parent than in Type 1 diabetic subjects whose parents were not diabetic. Second, a DR4-haplotype was transmitted from the Type 2 diabetic parent to the Type 1 offspring more often than expected. These data are consistent with the hypothesis that families with a Type 2 diabetic parent and Type 1 diabetic child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility. In this report, we further explore the relationship between the high-risk HLA antigen (HLA-DR4) in study subjects with differing glycaemic status (National Diabetes Data Group criteria). In this community-based study, we find evidence that HLA-DR4 is increased in study subjects with Type 2 diabetes and may be a marker for Type 2 diabetes susceptibility. PMID- 8462773 TI - Serum levels of growth hormone-binding protein and insulin-like growth factor I in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. AB - Serum levels of insulin-like growth factor I are reduced in patients with Type 1 (insulin-dependent) diabetes mellitus. To evaluate the role of the hepatic growth hormone receptor in the decreased serum concentrations of insulin-like growth factor I, serum levels of the high affinity growth hormone-binding protein, which is qualitatively and quantitatively related to the hepatic growth hormone receptor, and of insulin-like growth factor I were measured in 70 children and adolescents with Type 1 diabetes and 105 healthy control children. Analysis of variance revealed a significant negative effect of Type 1 diabetes on serum levels of the growth hormone-binding protein and of insulin-like growth factor I. In the diabetic patients, serum levels of the growth hormone-binding protein were positively related to body mass index and to insulin dose per kg body weight, and were not influenced by pubertal stage, gender, or plasma levels of haemoglobin A1c. Serum levels of insulin-like growth factor I increased during early puberty reaching peak levels at mid-puberty and decreasing thereafter. No relationship was found between serum levels of growth hormone-binding protein and of insulin like growth factor I. Our data suggest that decreased liver somatogenic receptor levels, as reflected by the concentrations of circulating growth hormone-binding protein, play a minor role in the suppressed concentrations of circulating insulin-like growth factor I. Post-growth hormone receptor defects or changes in the insulin-like growth factor binding proteins probably contribute more to the lower serum levels of insulin-like growth factor I. PMID- 8462774 TI - Size- and charge selectivity of glomerular filtration in Type 1 (insulin dependent) diabetic patients with and without albuminuria. AB - Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30-100 mg/24 h in group D2; 101-300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 mumol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of beta 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 A fractions in the range 26-64 A) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p < 0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 A dextran (p < 0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy. PMID- 8462775 TI - Both DQA1 and DQB1 genes are implicated in HLA-associated protection from type 1 (insulin-dependent) diabetes mellitus in a British Caucasian population. AB - Inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus is partly determined by HLA genes. It has been suggested that protection from disease may be conferred by HLA-DQB1 genes which encode molecules with aspartate at position 57. We investigated the contributions of HLA-DRB1, DQA1 and DQB1 genes to protection from disease. Restriction fragment length polymorphism and sequence specific oligonucleotide analysis in 156 British Caucasian Type 1 diabetic and 116 control subjects showed protection from disease was associated with DR2, DRw6 and DR7 haplotypes. The most protective DQA1 allele was DQA1*0102 which occurred on both DR2 and DRw6 haplotypes. The DQB1 alleles DQB1*0303, DQB1*0602 and DQB1*0603 were associated with protection, as was DQB1*0604, which encodes an Asp-57 negative DQ beta molecule. Heterozygosity for both protective and predisposing HLA markers was reduced in diabetic compared with control subjects. We conclude that both DQA1 and DQB1 genes are implicated in HLA associated protection from Type 1 diabetes in this British Caucasian population. The overall structure of the DQ heterodimer is critical and DQ beta-Asp 57 is of secondary importance in determining protection from disease. The effect of protective HLA types may predominate over that of predisposing markers. PMID- 8462776 TI - Metabolism by human endothelial cells of very low density lipoprotein subfractions isolated from type 1 (insulin-dependent) diabetic patients. AB - The very low density lipoprotein (VLDL) fraction was isolated from 11 normolipidaemic Type 1 (insulin-dependent) diabetic patients in good to fair glycaemic control and from 11 age-, sex- and race-matched, non-diabetic, control subjects. The rate of receptor-mediated degradation by human endothelial cells was significantly greater (p < 0.02) for the total VLDL fraction isolated from diabetic patients compared to control subjects and averaged 1008 +/- 300 and 717 +/- 150 ng.mg cell protein-1.16 h-1, respectively. The total VLDL fraction was separated into three subfractions: VLDL-I, Sf 100-400 (Sf = Svedberg units); VLDL II, Sf 60-100; VLDL-III, Sf 20-60. Rates of receptor-mediated degradation of VLDL I and VLDL-II isolated from diabetic patients were significantly greater than the comparable subfraction isolated from control subjects and averaged 1023 +/- 279 vs 361 +/- 122 (p < 0.01) and 433 +/- 70 vs 294 +/- 70 ng.mg cell protein-1.16 h 1 (p < 0.03), respectively. Rates of receptor-mediated degradation of the V-III subfraction isolated from the two groups did not differ significantly. There were no significant differences in the chemical composition or in the plasma concentrations of the VLDL subfractions isolated from diabetic patients compared to control subjects. There was a significant increase in the apoprotein E content of VLDL-I (p < 0.01) and VLDL-II (p < 0.05) isolated from diabetic patients. There was a significant increase in the ratio of apoprotein C compared to apoprotein E (p < 0.03) in VLDL-I isolated from control subjects compared to the diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462777 TI - Diabetes mellitus and hypertension: the possible role of hyperglycaemia through oxidative stress. PMID- 8462779 TI - Increasing opportunities for women benefits the entire research community. PMID- 8462778 TI - Infant nutrition and subsequent risk of type 2 (non-insulin-dependent) diabetes mellitus. PMID- 8462780 TI - Effects of spaceflight on the musculoskeletal system: NIH and NASA future directions. AB - Prolonged bed rest, undertaken by volunteers or resulting from injury and disease, can impair bone and muscle function and structure; extended travel in space also induces these effects. Fluid shifts and disrupted fluid balance may also contribute to observed musculoskeletal aberrations in the weightless environment. Some molecular and cellular events involved in the loading and unloading of the musculoskeletal system are under neural and endocrine influence or control, whereas other events are influenced by local growth factors. Studies are in progress to develop interventions that preserve or improve musculoskeletal integrity in 1g. The NIAMS and NASA are interested in basic and clinical studies of the influence of microgravity on the musculoskeletal system. The interagency workshop results form the basis for new collaborative and cooperative research emphases for the biomedical community under a broad agreement between the National Institutes of Health and NASA. PMID- 8462781 TI - The design and application of residualizing labels for studies of protein catabolism. AB - Residualizing labels (R-labels) are chemical tags for proteins, originally designed for studies of the sites and mechanisms of plasma protein catabolism. The labels consist of oligosaccharides derivatized with radioactive, fluorescent, nuclear magnetic resonance (NMR), or positron emission tomography (PET) active reporter molecules. Because these glycoconjugates generally have molecular masses in excess of 500 daltons and are hydrophilic, they are relatively membrane impermeant. They are also designed to be resistant to lysosomal hydrolases and are therefore retained inside cells with half-lives of 2-5 days after endocytosis and degradation of the carrier protein. The R-labels thus provide a convenient means for following the cumulative uptake and catabolism of proteins by cells in vivo or in vitro. This review summarizes how R-labels have provided insights into the sites and regulation of the turnover of circulating proteins, and pathways for intracellular transport and degradation of endocytosed proteins. The potential use of R-labels for noninvasive studies of the distribution of protein pharmaceuticals in vivo is also discussed. PMID- 8462782 TI - Coaggregation: specific adherence among human oral plaque bacteria. AB - Nearly all human oral bacteria exhibit coaggregation, cell-to-cell recognition of genetically distinct cell types. Clumps or coaggregates composed of the two kinds of cells are formed immediately upon mixing two partner cell types. Members of all 18 genera tested exhibit lactose-reversible coaggregation. Many of these interactions appear to be mediated by a lectin on one cell type that interacts with a complementary carbohydrate receptor on the other cell type. A lactose sensitive adhesin has been isolated from Prevotella loescheii PK1295, and it exhibits the adherence properties observed with whole cells. Other adhesins have been identified and the genes for some of them have been cloned and sequenced. One Streptococcus sanguis adhesin is a lipoprotein that appears to have a dual function of recognizing both a bacterial carbohydrate receptor and a receptor in human saliva. Carbohydrate receptors for some adhesins have been purified from five oral streptococci, and they specifically block the coaggregations with the streptococcal partners that express the complementary adhesins. Coaggregation offers an explanation for the temporally related accretion of dental plaque and bacterial recognition of mucosal surfaces. Early colonizers of the tooth surface coaggregate with each other and late colonizers of the tooth surface coaggregate with each other, but with few exceptions, early colonizers do not recognize late colonizers. Furthermore, bacteria that colonize mucosal surfaces coaggregate with each other, indicating the high degree of specificity of coaggregation in the oral bacterial population. PMID- 8462783 TI - Is dehydroepiandrosterone an antiobesity agent? AB - The steroid hormone intermediate, DHEA, has been proposed as a therapeutic agent for the treatment of obesity. Its effects on lipogenesis, substrate cycling, peroxisome proliferation, mitochondrial respiration, protein synthesis, and thyroid hormone function have been reported. The results of these studies suggest that the antiobesity function of DHEA is not simply one of inhibiting fat synthesis and deposition but is one of affecting a number of pathways that contribute to the maintenance of the isoenergetic state rather than the promotion of positive energy balance. PMID- 8462784 TI - Role of the CD45 tyrosine phosphatase in signal transduction in the immune system. AB - CD45, a family of hematopoietic cell specific surface antigens, is the best characterized protein tyrosine phosphatase described to date. Considerable evidence from a number of laboratories suggests that surface expression of this molecule is required for normal signaling events to occur in T lymphocytes, B lymphocytes, and natural killer cells. In this paper, data supporting this contention are reviewed and a model proposing how CD45 may exert its regulatory function on signal transduction via the T cell antigen receptor is presented. PMID- 8462785 TI - Idiotypes: structure and immunogenicity. AB - Idiotopes are markers on the variable domains of antigen-specific immunological receptors recognized by anti-idiotypic antibodies or T cells. Therefore, a given antibody or T cell receptor can be identified on the basis of a characteristic idiotypic pattern. The structural correlates for idiotopes on antibodies have been studied by competitive binding assays, electron microscopy, site-directed mutagenesis, and X-ray crystallography. Immunoglobulin idiotopes, recognized by antiidiotypic antibodies, can involve amino acid residues from several hypervariable or framework regions and from either or both of the heavy and light chain variable domains. Recent studies suggest that it may be possible to exploit structural knowledge of idiotopes and anti-idiotopes for the design of new ligands for immunological or other cell surface receptors. In one instance, it has been possible to use the inferred structural features of an anti-idiotope, which mimics a viral protein, to design a small organic molecule with functional properties approximating those of the antigen and the native anti-idiotope. An alternative strategy being explored for creating new vaccines or therapeutic agents involves engineering an amino acid sequence, corresponding to a segment of a selected nominal antigen, into an immunoglobulin variable domain. PMID- 8462786 TI - Synthesis of vitamin K-dependent proteins. AB - The unique and characteristic feature of vitamin K-dependent proteins is the presence of gamma-carboxyglutamyl (Gla) residues formed during the posttranslational processing of these proteins. The energy needed to drive this microsomal carboxylation event comes from the reoxidation of the reduced, hydronaphthoquinone form of vitamin K to its 2,3-epoxide. Recent studies have suggested that an intermediate epoxide alkoxide is the strong base needed to abstract a proton from the relatively unreactive methylene carbon of the glutamyl residue. The primary gene product of the vitamin K-dependent proteins contains a homologous propeptide extension between the amino terminus of the mature protein and signal peptide. This region, which is cleaved before secretion of these proteins, serves to dock the protein substrate to the enzyme catalyzing the carboxylation event, and to also alter the apparent Km of the Glu binding site of the enzyme. The order in which the multiple Glu sites on the substrate proteins are carboxylated is unknown, but elucidation of this property of the enzyme and further details of the bioorganic mechanism should be aided by recent reports of purification of this unique carboxylase. PMID- 8462787 TI - Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. AB - Ca2+ accumulates in the nucleus and DNA undergoes enzymatic cleavage into internucleosome-length fragments before acetaminophen and dimethylnitrosamine produce hepatic necrosis in vivo and toxic cell death in vitro. However, Ca(2+) endonuclease fragmentation of DNA is characteristic of apoptosis, a type of cell death considered biochemically and functionally distinct from toxic cell death. The present studies investigate DNA fragmentation as a critical event in toxic cell death by testing whether the Ca(2+)-calmodulin antagonist chlorpromazine and the Ca2+ channel blocker verapamil prevent acetaminophen-induced hepatic necrosis by inhibiting Ca2+ deregulation and DNA damage. Acetaminophen overdose in mice produced accumulation of Ca2+ in the nucleus (358% of control) and fragmentation of DNA (250% of control) by 6 h, with peak release of ALT occurring at 12-24 h (38,000 U/l). Pretreatment with chlorpromazine prevented increases in nuclear Ca2+ and DNA fragmentation and nearly abolished biochemical evidence of toxic cell death. Verapamil pretreatment also decreased Ca2+ accumulation and DNA damage while attenuating liver injury. The Ca2+ antagonists did not protect against toxic cell death through hypothermia because neither produced the delay in toxicity that is customarily associated with hypothermia. Nor did chlorpromazine or verapamil protect through inhibiting acetaminophen bioactivation. Chlorpromazine failed to diminish glutathione depletion in whole liver and isolated nuclei. Verapamil (250 microM) also failed to alter glutathione depletion in whole liver and had no effect on acetaminophen glutathione adduct formation by mouse liver microsomes and by cultured mouse hepatocytes. Collectively, these results support the hypothesis that Ca(2+) induced DNA fragmentation plays a significant role in cell necrosis produced by acetaminophen and may contribute to toxic cell death caused by other alkylating hepatotoxins. PMID- 8462788 TI - Expression of the duck alpha-enolase/tau-crystallin gene in transgenic mice. AB - In many vertebrates, metabolic enzymes have been directly recruited to an additional structural role as crystallins in the eye lens. In some species the glycolytic enzyme alpha-enolase (alpha ENO) attains high concentrations in the lens, as tau-crystallin (tau CRY). A line of transgenic mice was constructed containing the entire duck alpha ENO/tau CRY gene with 5'- and 3'-flanking regions and all introns. Full-sized duck alpha ENO mRNA was expressed in the transgenic mice with the same pattern as the endogenous mouse alpha ENO isozyme. Although there was no evidence for tissue preference, the concentration of enolase increased markedly in transgenic lens as well as in other tissues. In spite of this, transgenic lenses were transparent and the animals were normal in appearance. The increase in enolase levels in the transgenic lens mimics the stepped increase that might occur in the early stages of enzyme crystallin recruitment. These results demonstrate that lens transparency is sufficiently robust to be refractory to some increase in metabolic enzyme concentration without the need for compensatory adaptation. PMID- 8462789 TI - Delayed internucleosomal DNA fragmentation in programmed cell death. AB - DNA fragmentation was evaluated in three instances of programmed cell death, interdigital cell death in embryonic mouse limbs, and metamorphic death of both the labial glands and intersegmental muscle in the tobacco hornworm Manduca sexta. In the mouse, we evaluated both developmental cell death and expanded range cell death induced by retinoic acid. The status of DNA was examined in several ways. Nuclei were examined by electron microscopy and Feulgen staining. Quantitative assessment of total DNA content in Feulgen-stained degenerating nuclei was made for the gland. In the labial gland, DNA content does not drop during the early phases of cell death; nor is an endonucleolytic ladder seen when DNA was examined by ethidium bromide staining or prelabeling with [3H]thymidine. Only by using end labeling of DNA could we detect DNA fragmentation at a very late stage in cell death, day 4 of the collapse of the gland. In contrast, WEHI 7.1 lymphoma cells display an early and extensive ladder after treatment with glucocorticoids. In mouse limb, for which cell death follows a more classic apoptotic morphology, a ladder is likewise not seen. We conclude that activation of an endonuclease is neither a trigger nor a necessary or defining component of the early phases of developmental programmed cell death, and that reported failure by others to find such a ladder may depend on limitations in the system that is under investigation. PMID- 8462790 TI - Studies on enzyme inhibition--50 years ago. PMID- 8462791 TI - Motilin and erythromycin stimulate pepsinogen secretion by chief cells isolated from guinea pig stomach. AB - BACKGROUND: Motilin and erythromycin bind the same receptor in the gastrointestinal muscle cells. Motilin stimulates pepsinogen secretion in humans and dogs. However, it is unclear whether it acts directly on gastric chief cells or via other neurotransmitters. METHODS: Isolated gastric chief cells were obtained from guinea pig stomach by collagenase digestion and calcium chelation with ethylene glycol-bis(B-amynomethyl ether)-N,N,N',N'-tetraacetic acid. RESULTS: Significant stimulation of pespinogen secretion induced by motilin occurred at 1 pmol/L, half maximum at 10 pmol/L, and maximum at 100 pmol/L. Erythromycin caused significant stimulation at 1 pmol/L, half maximum at 100 pmol/L, and maximum at 1 nmol/L. Atropine (1 mumol/L) had no effect on either motilin- or erythromycin-induced pepsinogen secretion. Motilin and erythromycin determined a threefold increase in the intracellular calcium concentrations. Pretreatment of isolated chief cells with motilin and erythromycin induced a reversible, dose- and time-dependent desensitization of the pepsinogen secretion stimulated by carbachol and cholecystokinin but not that stimulated by secretin, vasoactive intestinal peptide, or prostaglandin E2. CONCLUSIONS: Motilin and erythromycin directly stimulate pepsinogen secretion in isolated chief cells. PMID- 8462792 TI - Prognostic significance of K-ras mutations in colorectal carcinoma. AB - BACKGROUND: Mutations at codons 12, 13, and 61 of the ras genes have been found in a variety of human tumors and may have prognostic significance. K-ras mutations have been shown in 40%-50% of colorectal cancers. METHODS: Using a simple nonradioactive polymerase chain reaction-based technique, we have investigated the possible prognostic significance of point mutations of the K-ras gene in patients with human colorectal carcinomas. The prevalence and the type of ras mutations were compared between a group of 35 patients having recurrent disease within 5 years and a group of 64 patients who were disease free 5 years following surgery. RESULTS: First, we found that the overall prevalence of mutations within codons 12 and 13 of the K-ras gene was 25% in the nonrecurring group vs. 71% in the patients with recurrent disease (P < 0.0001) and, second, that mutations other than GGT to GAT occurred, with one exception, exclusively in recurring tumors. CONCLUSIONS: In Dukes' B and C primary tumors, mutations other than GGT to GAT identify patients at very high risk for recurrence. Our results indicate that determining the K-ras mutations provides a good prognostic factor in patients with advanced colorectal carcinoma. PMID- 8462793 TI - On the specificity of altered muscle function in experimental colitis in rats. AB - BACKGROUND: Studies on muscle contraction in colitis yield conflicting data that may reflect differences in the manner in which colitis is induced. Therefore, we compared distal colonic longitudinal muscle contraction in four models of colitis in the rat. METHODS: Distal colitis was induced by intrarectal administration of trinitrobenzene sulfonic, acetic acid, or Trichinella spiralis larvae, or by intraperitoneal injection of mitomycin C. Colonic myeloperoxidase activity was used to monitor acute inflammation. RESULTS: Myeloperoxidase activity increased in each model of colitis. In trinitrobenzene-treated rats, contractile responses to carbachol, substance P, and KCl decreased by 64%, 76%, and 58%, respectively. In acetic acid treated rats, responses induced by carbachol, substance P, or KCl were each significantly decreased by 73%, 68%, and 55% and were similarly reduced by 42%, 77%, and 46%, respectively, in rats with T. spiralis colitis. In mitomycin-induced colitis, these respective responses also decreased significantly by 71%, 55%, and 54%. CONCLUSION: Decreased contractility of longitudinal muscle in acute colitis in rats is independent of the manner in which the colitis is induced and is mediated at a receptor-independent locus on the muscle cell. PMID- 8462794 TI - Reflux-related gastric mucosal injury is associated with increased mucosal histamine content in humans. AB - BACKGROUND: Experimental studies in the dog and the rat have shown histamine involvement in reflux-related gastric mucosal injury. However, no definite demonstrations of a link between reflux-related gastric mucosal injury and mast cell mediators exist in humans. METHODS: The relationships between reflux, gastric mucosal histamine content, and gastric histology were assessed in partially gastrectomized subjects presumptively with high (11 Billroth II subjects) and low reflux levels (9 total biliary diversion subjects), respectively. Findings were compared with those in a control group consisting of 8 endoscopically and histologically proven normal subjects. RESULTS: Bile acid quantity and concentration in the gastric aspirates were significantly greater in Billroth II subjects than in total biliary diversion subjects. Significantly higher cumulative scores for foveolar hyperplasia, mucosal edema, capillary dilatation and congestion, and smooth muscle fibers in the lamina propria were found in Billroth II subjects than in total biliary diversion subjects. Mucosal histamine content as well as mast cell density and degranulation differed significantly between Billroth II and the other two groups. CONCLUSIONS: These results represent the first demonstration in humans of an association between mast cell mediators and chemical gastric mucosal injury. PMID- 8462795 TI - Gut lavage fluid protein concentrations: objective measures of disease activity in inflammatory bowel disease. AB - BACKGROUND: Fluid obtained by whole gut lavage normally contains traces of immunoglobulin (Ig) G, albumin, and alpha-1-antitrypsin; higher concentrations have been found in patients with inflammatory bowel disease (IBD). METHODS: In a prospective study, 53 lavages were performed in 45 IBD patients (27 Crohn's disease, 18 ulcerative colitis), in whom disease activity was simultaneously assessed by Crohn's Disease Activity Index or Powell Tuck index. Concentration of IgG in lavage fluid was measured by enzyme-linked immunosorbent assay, and of albumin and alpha-1-antitrypsin by immunoturbidimetry. RESULTS: For IgG, concentrations in lavage fluid correlated closely with activity indices: in Crohn's disease, r = 0.723 (P < 0.0001), in ulcerative colitis, r = 0.714 (P < 0.0001). Results for albumin and alpha-1-antitrypsin concentrations were similar to those for IgG, but they were less sensitive in detecting active disease. However, this method cannot be used as a diagnostic test for IBD; normal results were obtained for IgG in 6 (all inactive) of 42 lavages in patients who had unequivocal radiological or endoscopic abnormalities. CONCLUSIONS: Assay of protein concentrations in gut lavage fluid is a simple, objective means of grading disease activity in patients with IBD; its potential uses are likely to be in the evaluation of complex cases and in clinical trials. PMID- 8462796 TI - Nonsteroidal anti-inflammatory drugs and peptic ulcer hospitalization rates in New South Wales. AB - BACKGROUND: Consumption of nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDS) increased substantially during the 1980s. The effects of this trend on hospitalization rates for peptic ulcer in different age groups in New South Wales, Australia, was investigated. METHODS: A population model based on sales of NANSAIDS and aspirin, age specific estimates of the relative risk of ulcer complications with these drugs, and hospitalization data for 1979 through 1988 was created. RESULTS: All age groups increased consumption of NANSAIDS. The increases were greatest in elderly subjects, with women over age 65 years increasing the prevalence of their use of the drugs from 11.9% in 1979 to 22.5% in 1988 and males over age 65 increasing use from 9.7% to 20%. Aspirin use remained relatively unchanged in all age groups. Hospitalization rates for peptic ulcer decreased in both sexes under age 64 despite increasing use of NANSAIDs. Hospitalization increased in males and females over age 65, but in females the increase was substantially greater than predicted by the computer model. In women and men over age 75 the increases in hospitalization rates predicted by the model were only 18% and 33%, respectively, of the observed rises. CONCLUSIONS: The increasing hospitalization rate for peptic ulcer among elderly subjects was only partly explained by the increasing consumption of NANSAIDS. Further research is needed. PMID- 8462797 TI - Developmental expression of the gastrin and cholecystokinin genes in rat colon. AB - BACKGROUND: To elucidate the hypothesis that gastrin and cholecystokinin (CCK) are local growth factors for colorectal mucosa, we have examined the peptide gene expression in rat colon during development. METHODS: Northern analysis, reverse transcription PCR, and sequence-specific radioimmunoassays were the essential methods. RESULTS: High concentrations of gastrin and CCK messenger RNA were found in the fetal colon. At birth, gastrin and CCK mRNA's were both undetectable but increased subsequently towards adult life. The fetal colon contained 5.5 and 4.2 pmol/g tissue gastrin and CCK, respectively. After birth, carboxyamidated gastrin disappeared from the colon, whereas the concentration of CCK remained at 1 pmol/g. Glycine-extended gastrin and CCK were also present in the fetal colon, but towards adult life they decreased below 0.2 pmol/g. In contrast, progastrin and proCCK were detectable at all ages. CONCLUSIONS: Rat colon expresses the gastrin and CCK genes throughout life. The posttranslational maturation of progastrin, however, ceases shortly after birth, indicating that gastrin may play a role in the developing colon. Whether CCK influences the development remains to be shown. PMID- 8462798 TI - Expression but incomplete maturation of progastrin in colorectal carcinomas. AB - BACKGROUND: To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue. METHODS: Northern analysis, reverse transcription PCR, and a library of sequence-specific radioimmunoassays were the principal methods. RESULTS: Cell lines, tumors, and normal tissue all expressed a gastrin mRNA of 0.7 kilobases, and all cell lines contained incompletely processed progastrin (range, 17-54 fmol/10(6) cells). Two cell lines secreted progastrin into the media (LoVo, 25 +/- 3 pmol/L; HCT116; 12 +/- 2 pmol/L). Normal colonic tissue and all the solid tumors also contained progastrin, the concentration being higher in tumors (range, 0.4-2 pmol/g) than in normal tissue (range, 0.1-0.2 pmol/g). Only one tumor contained carboxyamidated gastrins. CONCLUSIONS: Normal and neoplastic colonic mucosa both express the gastrin gene, but the posttranslational phase of expression is attenuated. The incomplete processing and low level of expression suggest that autocrine gastrin secretion has only minor significance for normal adult and most neoplastic colonic tissue. PMID- 8462799 TI - Saccharomyces boulardii inhibits Clostridium difficile toxin A binding and enterotoxicity in rat ileum. AB - BACKGROUND: Saccharomyces boulardii is a nonpathogenic yeast used for the prevention and treatment of Clostridium difficile-associated diarrhea and colitis. However, the mechanism by which S. boulardii exerts its protective effects remains unclear. METHODS: The binding of [3H]toxin A to its brush border receptor preincubated with S. boulardii-cultured suspension or filtered conditioned medium was measured in vitro. The effect of toxin A on secretion, epithelial permeability, and morphology in rat ileal loops in vivo was also examined in rats pretreated with S. boulardii. RESULTS: S. boulardii reduced [3H]toxin A-receptor binding in a dose-dependent fashion. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of ileal brush border exposed to S. boulardii conditioned medium revealed a diminution of all brush border proteins. Treatment of rats with S. boulardii suspension reduced fluid secretion and mannitol permeability caused by toxin A. CONCLUSIONS: S. boulardii may reduce some of the enterotoxic effects of toxin A by inhibiting toxin A-receptor binding. This effect appears to be manifested by a secreted product of the yeast, possibly a protease. PMID- 8462800 TI - Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B. AB - BACKGROUND: The prognosis of advanced cirrhosis due to chronic hepatitis B is poor, and results of therapies, including liver transplantation, have been unsatisfactory. Little is known about the effectiveness of interferon alfa in patients with cirrhosis. METHODS: Between 1984 and 1991, 18 patients with clinically-apparent cirrhosis due to hepatitis B were treated with interferon alfa at the Clinical Center of the National Institutes of Health. RESULTS: Six treated patients (33%) had a sustained loss of hepatitis B virus DNA and hepatitis B e antigen (if present initially) and decrease of amino-transferase levels into the normal or near normal range. In follow-up, these 6 patients resolved all symptoms of cirrhosis and are alive and fully active. In contrast, the 12 patients who did not have a sustained loss of hepatitis B virus have had evidence of progressive liver disease, 6 have died and 4 underwent hepatic transplantation. Side effects of interferon were common and included bacterial infections (n = 5) and exacerbations of disease (n = 9). CONCLUSIONS: These findings indicate that interferon alfa is effective in selected patients with mildly decompensated cirrhosis due to hepatitis B. PMID- 8462801 TI - Recurrence of hepatitis D (delta) in liver transplants: histopathological aspects. AB - BACKGROUND: The viral/pathological correlates of recurrent hepatitis delta virus (HDV) disease in orthotoptic liver transplants are reported. METHODS: We examined the histological features of recurrent HDV disease in nine patients with transplants for terminal HDV cirrhosis were examined; intrahepatic HDV and hepatitis B virus (HBV) antigens were detected by immunoperoxidase techniques. Sera were tested for the battery of HDV and HBV markers. RESULTS: In four patients, HDV reinfection was accompanied by the recurrence of an HBV infection with features of active viral replication. In the other five, HDV reinfection was accompanied by an atypical recurrence of HBV infection without evidence of active HBV replication (no expression of intrahepatic hepatitis B core antigen). In four of the latter patients, the atypical HBV pattern changed during the follow-up into a pattern of active viral replication accompanied by chronic necroinflammation detected during histology. CONCLUSION: The pattern of recurrent HBV infection can influence the pathological aspects of the relapses of HDV disease in liver grafts. PMID- 8462802 TI - Immunogenicity of inactivated hepatitis A vaccine in children. AB - BACKGROUND: Inactivated hepatitis A vaccine is now becoming available in many countries. METHODS: To evaluate the immunogenicity and safety of inactivated hepatitis A vaccine in healthy children, 99 susceptible schoolchildren from 4 to 15 years of age received 360 enzyme-linked immunosorbent assay units of the inactivated hepatitis A vaccine at months 0, 1, and 6. RESULTS: Antibody to hepatitis A virus seroconversion (> or = 20 mIU/mL) was 97% (96/99) in vaccinees after the first dose and 100% after the second (99/99) and booster (96/96) doses. The geometric mean titers of antibody to hepatitis A virus were 167, 465, and 4133 mIU/mL after each dose of vaccine, respectively. There were no significant side effects during the vaccination. Levels of antibody to hepatitis A virus were also tested in 9 susceptible children at day 7 and months 1 and 4 after the intramuscular injection of 2 mL of immune serum globulin. All children had measurable titers of antibody to hepatitis A virus 1 week after receiving immune serum globulin by sensitive enzyme immunoassay, but measurable titers had disappeared 1-4 months later. CONCLUSIONS: The inactivated hepatitis A vaccine is safe and immunogenic in healthy children. PMID- 8462803 TI - Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with ascites. AB - BACKGROUND: This study was performed to investigate the risk factors for a first episode of spontaneous bacterial peritonitis in cirrhotic patients. METHODS: One hundred ten cirrhotics with sterile ascites, without previous spontaneous bacterial peritonitis (SBP), were included from March 1988 to October 1989 and followed up until October 1990 (follow-up, 46 +/- 3.5 weeks; range, 4-120 weeks). RESULTS: Twenty-eight patients (25.45%) suffered SBP. In multivariate analysis (Cox's regression model) including only variables commonly used in clinical practice, ascitic fluid protein concentration and serum bilirubin level independently correlated with first SBP development. Using these two variables the relative risk of a first SBP episode was calculated for each patient. According to the median relative risk coefficient (1.2), a low-risk group (relative risk, < 1.2) and a high-risk group (relative risk, > 1.2) were established. Kaplan-Meier estimates of patients free of SBP were significantly higher in the low-risk group. CONCLUSIONS: The probability of a first SBP episode is significantly influenced by the antimicrobial capacity of ascitic fluid and hepatic function. PMID- 8462804 TI - Arteriovenous shunting, hemodynamic changes, and renal sodium retention in liver cirrhosis. AB - BACKGROUND: Arterial vasodilation has been postulated to initiate sodium retention in cirrhosis. This work was designed to analyze whether arteriovenous shunting underlies vasodilation and influences renal function in cirrhosis. METHODS: The femoral arteriovenous difference in oxygen content (Ca-VO2) was measured in 10 healthy subjects (control group) and 31 cirrhotic patients: 9 without ascites (group 1), 10 with ascites and a urinary sodium excretion rate (UNaV) of > 10 mEq/24 h (group 2), and 12 with ascites and UNaV of < or = 10 mEq/24 h (group 3). In 8 subjects from each group, femoral blood flow and the cardiac output were determined by duplex-Doppler ultrasonography. In 9 cases arteriovenous shunting in the femoral territory was estimated using 30 +/- 5 microns radiolabeled microspheres. RESULTS: Ca-VO2 was lower in group 3 than in controls or group 1. Ca-VO2 correlated inversely with femoral blood flow, plasma renin activity, plasma aldosterone concentration, and degree of shunting measured by microspheres. Ca-VO2 correlated directly with systemic vascular resistance and prothrombin index. CONCLUSIONS: In decompensated cirrhotic patients, there is an increased arteriovenous shunt for oxygen in the lower extremities that is associated with increased arterial blood flow, decreased systemic vascular resistance, and worsening of liver function. This shunt is due partly to opening of arteriovenous precapillary connections. PMID- 8462805 TI - Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group. AB - BACKGROUND: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. METHODS: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. RESULTS: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placebo and gabexate mesilate groups. CONCLUSIONS: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis. PMID- 8462806 TI - Agenesis of the dorsal pancreas in a woman with diabetes mellitus and in both of her sons. AB - Complete agenesis of the dorsal pancreas has rarely been described. Complete agenesis of the dorsal pancreas in a female who developed insulin-dependent diabetes mellitus at the age of 39 years is reported. The diagnosis of agenesis of the dorsal pancreas was suspected by abdominal ultrasound and confirmed by abdominal computed tomography (CT), magnetic resonance imaging, and endoscopic retrograde pancreatography. Her exocrine pancreatic function was essentially normal. Both of the patient's sons also had agenesis of the body and tail of the pancreas verified by abdominal CT but had no evidence of diabetes mellitus. This familial occurrence of agenesis of the dorsal pancreas suggests that hereditary mechanisms may play a role in the pathogenesis of this anomaly. PMID- 8462807 TI - Ulcerative colitis and total alopecia in a mother and her son. AB - Extraintestinal autoimmune disorders are associated with ulcerative colitis in selected patients and lend support to the theory of immune-mediated injury in inflammatory bowel disease. Rarely, alopecia areata has been associated with ulcerative colitis, and familial aggregation and an HLA association have been reported for both disorders. The occurrence of both alopecia and ulcerative colitis in a mother and son are reported with a detailed investigation of antineutrophil cytoplasmic antibodies and HLA alleles in this family. Treatment with the immunosuppressive agent cyclosporine proved beneficial in the child leading to remission of the ulcerative colitis and nascent growth of scalp and body hair. PMID- 8462808 TI - Buerger's disease presenting as acute small bowel ischemia. AB - The case of a young man with an unusual presentation of thromboangiitis obliterans with ischemia of the small bowel, 2 years before peripheral vascular disease of the extremities was clinically expressed, is reported. PMID- 8462809 TI - What are functional bowel disorders? PMID- 8462810 TI - Cytokines and animal models: a combined path to inflammatory bowel disease pathogenesis. PMID- 8462811 TI - Regulatory peptides and intestinal growth. PMID- 8462812 TI - The problem with pouchitis. PMID- 8462813 TI - Damage prevention versus damage control in acute pancreatitis. PMID- 8462814 TI - Pancreas divisum: to stent or not to stent. PMID- 8462815 TI - Food allergy: fact, fiction, and fatality. PMID- 8462816 TI - Evolution of Barrett's esophagus: the jury is still out. PMID- 8462817 TI - Are early electron-microscopic acinar cell derangements in opossum pancreatitis critical for coagulative necrosis at 7 days? PMID- 8462818 TI - Preventing infection in cirrhotics with gastrointestinal hemorrhage. PMID- 8462819 TI - Bowel rest and elemental diet in Crohn's disease. PMID- 8462820 TI - Omega-3 fatty acids and bowel cancer. PMID- 8462821 TI - High risk, low mortality in chronic ulcerative colitis: explanation. PMID- 8462822 TI - The mechanism of bismuth absorption. PMID- 8462823 TI - Interleukin-2 activity of colonic lamina propria mononuclear cells in a rat model of experimental colitis. AB - BACKGROUND: Altered interleukin 2 (IL-2) production has been implicated in the pathogenesis of inflammatory bowel diseases. METHODS: The temporal relationship between IL-2, prostaglandin E2 (PGE2) production, and mucosal injury was evaluated by isolated colonic lamina propria mononuclear cells (LPMC), using the trinitrobenzene sulfonic acid model of rat colitis. RESULTS: Spontaneous LPMC IL 2 activity was significantly increased in chronic (5 weeks) but not acute (5 days) or resolved colitis groups. IL-2 activity after concanavalin A activation was highest in the groups with resolved and chronic colitis. PGE2 production was significantly increased in LPMC cultures in acute or chronic colitis as well as the ethanol control groups but not the resolved colitis group. The addition of indomethacin to LPMC cultures decreased PGE2 levels in all groups, whereas IL-2 activity increased only for the chronic and resolved colitis groups. No correlation was found between PGE2 and IL-2 production by LPMC. CONCLUSIONS: In this experimental model, LPMC IL-2 production varied according to the severity and duration of the inflammation. Increased PGE2 production does not appear to be responsible for the IL-2 alterations in colitis. PMID- 8462824 TI - Evaluation of the inflammatory infiltrate in pouchitis with 111In-labeled granulocytes. AB - BACKGROUND: The aim of this study was to elucidate the inflammatory infiltrate in pouchitis and define the changes following metronidazole therapy. METHODS: Twenty seven patients underwent functional grading, sigmoidoscopic and histological scoring, 111In-labeled granulocyte scanning, and 4-day fecal collections for 111In-labeled granulocyte excretion. Six of the patients with pouchitis underwent repeat studies after 1-month treatment with metronidazole, 400 mg three times daily. RESULTS: The grade of macroscopic inflammation in the pouch mucosa (sigmoidoscopic score) correlated well with the acute histological score (P < 0.0001), chronic histological score (P < 0.001), 4-hour 111In scan (P < 0.001), 24-hour 111In scan (P < 0.001), and with 4-day fecal 111In excretion (P < 0.001). After metronidazole therapy there was decreased inflammatory grade sigmoidoscopically and histologically on the 4- and 24-hour scans and decreased 4 day fecal 111In granulocyte excretion. CONCLUSIONS: This study confirms that the inflammatory infiltrate in pouchitis is acute or chronic, is characterized by neutrophils, is usually localized to pouch mucosa, and is always decreased after metronidazole therapy. PMID- 8462825 TI - [Management of mono-amnion twin pregnancy]. AB - There have been only a few reports on monoamniotic twin pregnancies from the period of modern perinatology. Consequently, available recommendations about the management of these high-risk pregnancies are uncertain. In this study, we present the management and the outcome of three monoamniotic twin pregnancies and two further pregnancies with acardiac acephalus twin in comparison to other case reports and case series from the literature. Practical ways of caring for these high-risk pregnancies are outlined, emphasising the continuous search for entanglement of umbilical cord by ultrasound and cardiotocography. The special importance of intensified cardiotocographic monitoring is demonstrated. PMID- 8462826 TI - [Echographic evaluation of the integrity of adnexa tumors]. AB - The preoperative diagnosis of pelvic tumours is getting more and more important. This has special relevance to the increasing possibilities of conservative management of adnexal tumours and cysts (puncturing or operating by laparoscopy). We reviewed sonographical and histological data of 514 patients, who were operated on in the 2nd Department of Obstetrics and Gynaecology in Vienna because of pelvic masses. We correlated sonographical parameters like size of tumour, distinctness of margins, different kinds of internal echo pattern, papillary vegetation on the cystic wall or septa, with the defined histopathological diagnosis. A close relationship between size of tumour and tumour status could be found. The size of benign tumours was 7.1 cm. Malignant tumours had a size of 10.7 cm. The size of the high-echogenic area within the tumour, as well as its homogeneity, seemed to be of great importance. Such tumours with high-echogenic areas within, and especially those who had nonhomogeneous structures of these areas, proved to be malignant in 81% of the cases. Similarly, we found a close correlation of papillary vegetation either on cystic walls or on septa with the confirmed diagnosis of malignancy. Septa without papillarities or changing of their thickness were less important. By means of using our criteria a less experienced sonographic examiner could reach as good results as an experienced one in predicting malignancy. PMID- 8462827 TI - [Success and quality control in prolapse and stress incontinence operations- comparative use of urodynamics and transrectal endosonography]. AB - We evaluated the significance of urodynamic parameters versus transrectal ultrasound with regard to postoperative outcome-control after operation for procedentia and urinary stress incontinence. We studied 30 continent women and 84 women with purely stress induced urinary incontinence. All had a pre- and postoperative urodynamic testing including urethral profilometry and cystometry, paralleled by a transrectal ultrasound examination. From the urodynamic parameters only the transmission ratio is suitable to judge the surgical outcome, although it is less correlative to the patient's complaints (p = 0.033) than the bladder neck mobility (p < 0.0001, Tab. 5). Within the rather short time of follow-up, each of the operation-techniques was able to improve the bladder neck mobility significantly. Nevertheless, anterior colporrhaphia is not suitable for incontinence-surgery (Fig. 2/Tab. 5). Concerning operative results, transrectal endosonography was found to be an adequate or even superior method as compared to urodynamic studies, because it can likewise demonstrate the function of the bladder neck, but furthermore can show the morphologic aspects of bladder, urethra and pelvic floor. As a result, for the first time, this minimal invasive method offers quality control for the individual surgeon as well as for long-term follow-up studies after operation for procedentia and stress induced urinary incontinence without using much time or causing great discomfort to the patient. PMID- 8462828 TI - [SHBG serum level in women with endometriosis before, during and after long-term danazol therapy]. AB - Ten patients with endometriosis, aged from 21 to 37 years, were treated with danazol at a dosage level of 200 mg three times daily for 6 months. Three blood samples were drawn 60 min apart for evaluation of the sex hormone binding globulin (SHBG), before danazol administration (4th day of the cycle), during the last two weeks of the six-month therapy and three months after the cessation of treatment (4th day of the cycle). In contrast to that, SHBG levels were also evaluated in ten normal women, aged 21-37 years (4th day of the cycle). It was found that: a) SHGB values were significantly higher in patients with endometriosis than in the control group (p < 0.01), b) danazol resulted in significant decrease of SHBG levels (p < 0.001), c) there was no correlation between SHBG levels before and during danazol administration, and d) SHBG levels were significantly lower three months after the cessation of danazol than before the administration of the medication (p < 0.05), while these levels were not significantly different, compared with those of normal women. Our results support the view, that SHBG production disturbances might interfere with the possible pathogenetic mechanisms of infertility observed in endometriosis. PMID- 8462829 TI - [Women after surgically corrected vaginal aplasia: a follow-up of psychosexual rehabilitation]. AB - In 24 patients with Mayer-Rokitansky-Kustner syndrome we carried out a post operative follow-up examination. In the majority of cases, the operation had yielded functionally satisfactory results. 20 out of 24 of the patient collective now lead a healthy sexual life with an unimpaired emotional and sexual responsiveness. Early and regular postoperative cohabitation is vital for long term success of surgical results and more important than regular of the wearing phantom. A successful operation greatly increases the patient's self-esteem, her feeling of being sexually attractive, and her self-confidence. Despite general satisfaction with operational results, several women voiced criticism about inadequate perioperative psychological support. The patients' legitimate need for psychological help and guidance must not be neglected. This can take the form of regular discussions, in which detailed explanations about the disorder are given and which must also cover the subject of infertility, a cause of particular anguish in most women. This approach will contribute to enhancing the women's emotional stability and help them to better cope with their problems. It is our experience, that it is beneficial to include the patient's partner in such counselling. PMID- 8462830 TI - [Pelviscopic ovarian surgery: a new method of safe organ preserving surgery]. AB - For pelviscopic removal of ovarian tumours, a puncture or morcellation of the tumour used to be necessary, frequently causing the peritoneal cavity to be contaminated with contents of cysts or tumourous material. This contamination can be avoided safely by placing the intact tumour into a bag, provided that the tumour has been dissected completely. The intact tumour is put into a bag and both are completely removed at the same time through the abdominal wall. This method increases the safety of pelviscopic ovarian surgery, and its indication for use can be broadened. PMID- 8462831 TI - [Hydronephrosis in pregnancy]. AB - This is a report on the clinical course of a severe right-sided urinary retention in 21-year old patient, treated from the 24th week of pregnancy onwards. The special importance of the mechanical component involved in the genesis of this retention of urine is discussed on the occasion of the transitory spontaneous remission, observed, when the foetus turned to breech presentation. PMID- 8462832 TI - [Low-dose methotrexate in treatment of extra-uterine pregnancy]. PMID- 8462833 TI - [Eclampsia and HELLP syndrome in puerperium]. AB - We report on a case of a 34-year-old I. Grav./I. Para. After a normal pregnancy and Caesarean section, the patient developed a postpartum HELLP-syndrome with an eclamptic attack. PMID- 8462834 TI - [Adjuvant chemo- and hormone therapy of breast cancer]. AB - During the past few years "consensus statements" on the adjuvant treatment of patients with breast cancer have been issued periodically (the last one in the spring of 1992). Many physicians have interpreted such a tabellary synopsis as a "push-button" treatment, which is, of course, beside the point, since the text of the original publications for several subgroups of patients defines this treatment as "optional". In fact, physicians cannot decide by themselves, which treatment a patient should have. All patients must be shown both sides of the medal, i.e. a small chance to live longer and the risk of side effects, and finally each individual patient has to decide for herself on the basis of "informed consent". In case of widespread acceptance, as mentioned by some authors, that nearly all patients should be treated in some adjuvant manner, a large group which does not need any adjuvant treatment at all, will remain undefined. This group comprises at least 50% of all women ever treated for primary breast cancer. All physicians should consider it to be an urgent responsibility to define this group. This can be achieved only by means of studies, which include untreated or placebo-treated controls. PMID- 8462835 TI - [Importance of plasma PMN granulocyte elastase concentration determination in pregnant patients with premature rupture of fetal membranes]. AB - The aetiology of preterm rupture of membranes is not yet completely understood. Local infections of the vagina and cervix have attracted special attention during the last years. Ascending infection with subsequent chorioamnionitis is a common complication of preterm rupture of membranes. Recognition of the beginning of a chorioamnionitis is usually based on clinical symptoms and laboratory findings like white blood cell count and C-reactive protein. The purpose of this study was to find out the diagnostic value of elastase, a protease of polymorphonuclear granulocytes, which is known to be involved in inflammatory processes. Fifteen out of thirty-three patients with preterm rupture of membranes developed a chorioamnionitis. Elastase plasma concentration levels > or = 32 ng/ml one day before delivery showed a significant correlation (p = 0.02) to the development of a chorioamnionitis. At this time neither white blood cell count, nor rectal body temperature showed significant correlations. Low elastase levels do not exclude an infection, whereas high levels indicate an infectious process. We conclude that elastase is a relevant marker of chorioamnionitis. PMID- 8462836 TI - [Diagnosis of rupture of fetal membranes: comparison of vaginal detection of fetal fibronectin and intra-amnion injection of indigo carmine]. AB - Amniotic fluid contains a heavily glycosylated pregnancy-related isoform of fibronectin (fFN), which can be detected using FDC-6, a monoclonal antibody directed against a novel epitope specific to fFN. It has been identified in the amniotic fluid in various concentrations throughout the different pregnancy periods and is localised at the interface of the chorion and the uterine decidua. Because of the unique pregnancy-associated expression of fFN, we determined the utility of cervicovaginal appearance of fFN as a marker of membrane integrity or rupture of membranes. In a prospective study we compared 1) the detection of fFN in cervicovaginal samples by a membrane-immunoassay (ROM-Check, Mast Diagnostica, Reinfeld, FRG) with 2) the results of intraamniotic injection of Indigo Carmine (IC), followed by the observation of dye spill into the vagina to confirm rupture of membranes. 65 patients were examined, 12 patients had to be excluded from the study for various reasons. Examination results were identical in 50 patients, while in three cases the fFN results were positive with a simultaneous negative result of the intraamniotic dye injection. In the case of blood contamination, the fFN test results were not valid; testing of maternal blood and of urine samples was fFN negative in all cases. We conclude, that oncofoetal fibronectin is an excellent marker for rupture of membranes. The test is easy to perform and does not involve the risk of an intraamniotic injection of dye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462837 TI - [Folic acid supply in pregnancy--results of a prospective longitudinal study]. AB - After discussing the problem of folic acid requirements and supply during pregnancy, the results of a longitudinal study on 162 pregnant women are presented. By measuring biochemical and morphological changes in two subgroups (non-substituted vs unspecifically substituted), the necessity of a substitution with folic acid is discussed, as there might be additional requirements for the pregnant and the foetal organism. Concentrations of folic acid in the maternal plasma and in the erythrocytes as well as the segmentation rate and hypersegmentation of the granulocytes show a clear decrease in pregnancy. At the same time there was a significant difference between the subjects substituted and not substituted; the foetus and newborn levels were much higher than their mothers' concentrations. Moreover, there was a correlation between red cells folic acid levels in the last trimester and duration and outcome of pregnancy. These results indicate a substitution with folic acid for certain populations in pregnancy, which are highlighted. PMID- 8462838 TI - William Ernest Castle, pioneer mammalian geneticist. PMID- 8462839 TI - Evolution of natural transformation: testing the DNA repair hypothesis in Bacillus subtilis and Haemophilus influenzae. AB - The hypothesis that the primary function of bacterial transformation is DNA repair was tested in the naturally transformable bacteria Bacillus subtilis and Haemophilus influenzae by determining whether competence for transformation is regulated by DNA damage. Accordingly, DNA damage was induced by mitomycin C and by ultraviolet radiation at doses that efficiently induced a known damage inducible gene fusion, and the ability of the damaged cultures to transform was monitored. Experiments were carried out both under conditions where cells do not normally become competent and under competence-inducing conditions. No induction or enhancement of competence by damage was seen in either organism. These experiments strongly suggest that the regulation of competence does not involve a response to DNA damage, and thus that explanations other than DNA repair must be sought for the evolutionary functions of natural transformation systems. PMID- 8462840 TI - The Cs sec mutants of Escherichia coli reflect the cold sensitivity of protein export itself. AB - We have found that temperature can have a striking effect upon protein export in Escherichia coli, suggesting that there is a cold-sensitive step in the protein export pathway. Cs mutations comprise the largest class of mutations affecting the membrane-localized Sec proteins SecD, SecE, SecF and SecY. Although some of these mutations could encode cold-labile proteins, this is unlikely to account for the Cs phenotype of most export mutants, as mutations which simply produce lower amounts of SecE protein have the same phenotype. Certain signal sequence mutations affecting maltose binding protein are also cold sensitive for export. These effects appear to arise by a specific interaction of cold with certain export defects. We believe that the Cs sec mutations are representative of a large class of conditional lethal mutations, whose conditional phenotype reflects an underlying thermal sensitivity of the process in which they are involved. PMID- 8462842 TI - A conditional allele of the Saccharomyces cerevisiae HOP1 gene is suppressed by overexpression of two other meiosis-specific genes: RED1 and REC104. AB - The HOP1 gene of Saccharomyces cerevisiae is believed to encode a protein component of the synaptonemal complex, the structure formed when homologous chromosomes synapse during meiotic prophase. Five new mutant alleles (three conditional, two nonconditional) of HOP1 were identified by screening EMS mutagenized cells for a failure to complement the spore viability defect of a hop1 null allele. Two high copy plasmids were found that partially suppress the temperature-sensitive spore inviability phenotype of one of these alleles, hop1 628. The suppression is allele-specific; no effect of the plasmids is observed in hop1 null diploids. Mutation of either of the two suppressor genes results in recessive spore lethality, indicating that these genes play important roles during meiosis. The DNA sequence of one high copy suppressor gene matched that of RED1, a previously identified meiosis-specific gene. Our data strongly support the idea that RED1 protein is also a component of the synaptonemal complex and further suggest that the RED1 and HOP1 gene products may interact. The second suppressor maps to the right arm of chromosome VIII distal to CDC12 and is REC104, a meiosis-specific gene believed to act early in meiosis. PMID- 8462841 TI - Genetic evidence for transcriptional activation by the yeast IME1 gene product. AB - IME1 is required in yeast for meiosis and for expression of IME2 and other early meiotic genes. IME1 is a 360-amino acid polypeptide with central and C-terminal tyrosine-rich regions. We report here that a fusion protein composed of the lexA DNA-binding domain and IME1 activates transcription in vivo of a reporter gene containing upstream lexA binding sites. Activation by the fusion protein shares several features with natural IME1 activity: both are dependent on the RIM11 gene product; both are impaired by the same ime1 missense mutations; both are restored by intragenic suppressors. The central tyrosine-rich region is sufficient to activate transcription when fused to lexA. Deletion of this putative activation domain results in a defective IME1 derivative. Function of the deletion derivative is restored by fusion to the acidic Herpesvirus VP16 activation domain. The C-terminal tyrosine-rich region is dispensable for transcriptional activation; rather it renders activation dependent upon starvation and RIM11. Immunofluorescence studies indicate that an IME1-lacZ fusion protein is concentrated in the nucleus. These observations are consistent with a model in which IME1 normally stimulates IME2 expression by providing a transcriptional activation domain at the IME2 5' regulatory region. PMID- 8462843 TI - Meiotic mismatch repair quantified on the basis of segregation patterns in Schizosaccharomyces pombe. AB - Hybrid DNA with mismatched base pairs is a central intermediate of meiotic recombination. Mismatch repair leads either to restoration or conversion, while failure of repair results in postmeiotic segregation (PMS). The behavior of three G to C transversions in one-factor crosses with the wild-type alleles is studied in Schizosaccharomyces pombe. They lead to C/C and G/G mismatches and are compared with closely linked mutations yielding other mismatches. A method is presented for the detection of PMS in random spores. The procedure yields accurate PMS frequencies as shown by comparison with tetrad data. A scheme is presented for the calculation of the frequency of hybrid DNA formation and the efficiency of mismatch repair. The efficiency of C/C repair in S. pombe is calculated to be about 70%. Other mismatches are repaired with close to 100% efficiency. These results are compared with data published on mutations in Saccharomyces cerevisiae and Ascobolus immersus. This study forms the basis for the detailed analysis of the marker effects caused by G to C transversions in two factor crosses. PMID- 8462844 TI - Marker effects of G to C transversions on intragenic recombination and mismatch repair in Schizosaccharomyces pombe. AB - G to C transversion mutations show very strong allele-specific marker effects on the frequency of wild-type recombinants in intragenic two-factor crosses. Here we present a detailed study of the marker effect of one representative, the ade6 M387 mutation of Schizosaccharomyces pombe. Crosses of M387 with other mutations at varying distance reveal highly increased prototroph frequencies in comparison with the C to T transition mutation ade6-51 (control without any known marker effect) located four nucleotides from M387. The marker effect of M387 is strongest (> 40-fold) for crosses with mutations less than 15 nucleotides from M387. It decreases to an intermediate level (5-10-fold) in crosses with mutations located 25-150 base pairs from M387/51 and is very low in crosses with mutations beyond 200 base pairs. On the basis of these results and the quantitation of the low efficiency of C/C mismatch repair presented in the accompanying publication we propose the existence of at least two different types of mechanisms for base mismatch repair in fission yeast. The major system is suggested to recognize all base mismatches except C/C with high efficiency and to generate long excision tracts (approximately 100 nucleotides unidirectionally). The minor system is proposed to recognize all base mismatches including C/C with low and variable efficiency and to have short excision tracts (approximately 10 nucleotides unidirectionally). We estimate from the M387 marker effect that the minor system accounts for approximately 1-8% repair of non-C/C mismatches (depending on the nature of the mutation) in fission yeast meiosis. PMID- 8462845 TI - A mutational analysis of killer toxin resistance in Saccharomyces cerevisiae identifies new genes involved in cell wall (1-->6)-beta-glucan synthesis. AB - Recessive mutations leading to killer resistance identify the KRE9, KRE10 and KRE11 genes. Mutations in both the KRE9 and KRE11 genes lead to reduced levels of (1-->6)-beta-glucan in the yeast cell wall. The KRE11 gene encodes a putative 63 kD cytoplasmic protein, and disruption of the KRE11 locus leads to a 50% reduced level of cell wall (1-->6)-glucan. Structural analysis of the (1-->6)-beta-glucan remaining in a kre11 mutant indicates a polymer smaller in size than wild type, but containing a similar proportion of (1-->6)- and (1-->3)-linkages. Genetic interactions among cells harboring mutations at the KRE11, KRE6 and KRE1 loci indicate lethality of kre11 kre6 double mutants and that kre11 is epistatic to kre1, with both gene products required to produce the mature glucan polymer at wild-type levels. Analysis of these KRE genes should extend knowledge of the beta glucan biosynthetic pathway, and of cell wall synthesis in yeast. PMID- 8462846 TI - Mutational analysis of pre-mRNA splicing in Saccharomyces cerevisiae using a sensitive new reporter gene, CUP1. AB - We have developed a new reporter gene fusion to monitor mRNA splicing in yeast. An intron-containing fragment from the Saccharomyces cerevisiae ACT1 gene has been fused to CUP1, the yeast metallothionein homolog. CUP1 is a nonessential gene that allows cells to grow in the presence of copper in a dosage-dependent manner. By inserting previously characterized intron mutations into the fusion construct, we have established that the efficiency of splicing correlates with the level of copper resistance of these strains. A highly sensitive assay for 5' splice site usage was designed by engineering an ACT1-CUP1 construct with duplicated 5' splice sites; mutations were introduced into the upstream splice site in order to evaluate the roles of these highly conserved nucleotides in intron recognition. Almost all mutations in the intron portion of the 5' consensus sequence abolish recognition of the mutated site, while mutations in the exon portion of the consensus sequence have variable affects on cleavage at the mutated site. Interestingly, mutations at intron position 4 demonstrate that this nucleotide plays a role in 5' splice site recognition other than by base pairing with U1 snRNA. The use of CUP1 as a reporter gene may be generally applicable for monitoring cellular processes in yeast. PMID- 8462847 TI - Linkage group XIX of Chlamydomonas reinhardtii has a linear map. AB - Linkage group XIX (or the UNI linkage group) of Chlamydomonas reinhardtii has been reported to show a circular meiotic recombination map. A circular map predicts the existence of strong chiasma and chromatid interference, which would lead to an excess number of two-strand double crossovers during meiosis. We have tested this prediction in multipoint crosses. Our results are consistent with a linear linkage group that shows positive chiasma interference and no chromatid interference. Chiasma interference occurs both within arms and across the centromere. Of the original loci that contributed to the circular map, we find that two map to other linkage groups and a third cannot be retested because the mutant strain that defined it has been lost. A second reported unusual property for linkage group XIX was the increase in meiotic recombination with increases in temperature during a period that precedes the onset of meiosis. Although we observed changes in recombination frequencies in some intervals on linkage group XIX in crosses to CC-1952, and in strains heterozygous for the mutation ger1 at 16 degrees, we also show that our strains do not exhibit the previously observed patterns of temperature-sensitive recombination for two different pairs of loci on linkage group XIX. We conclude that linkage group XIX has a linear genetic map that is not significantly different from other Chlamydomonas linkage groups. PMID- 8462848 TI - Feedback control of sex determination by dosage compensation revealed through Caenorhabditis elegans sdc-3 mutations. AB - In Caenorhabditis elegans, sex determination and dosage compensation are coordinately controlled through a group of genes that respond to the primary sex determination signal. Here we describe a new gene, sdc-3, that also controls these processes. In contrast to previously described genes, the sex determination and dosage compensation activities of sdc-3 are separately mutable, indicating that they function independently. Paradoxically, the sdc-3 null phenotype fails to reveal the role of sdc-3 in sex determination: sdc-3 null mutations that lack both activities disrupt dosage compensation but cause no overt sexual transformation. We demonstrate that the dosage compensation defect of sdc-3 null alleles suppresses their sex determination defect. This self-suppression phenomenon provides a striking example of how a disruption in dosage compensation can affect sexual fate. We propose that the suppression occurs via a feedback mechanism that acts at an early regulatory step in the sex determination pathway to promote proper sexual identity. PMID- 8462849 TI - The genetics of feeding in Caenorhabditis elegans. AB - The pharynx of Caenorhabditis elegans is a nearly self-contained neuromuscular organ responsible for feeding. To identify genes involved in the development or function of the excitable cells of the pharynx, I screened for worms with visible defects in pharyngeal feeding behavior. Fifty-two mutations identified 35 genes, at least 22 previously unknown. The genes broke down into three broad classes: 2 pha genes, mutations in which caused defects in the shape of the pharynx, 7 phm genes, mutations in which caused defects in the contractile structures of the pharyngeal muscle, and 26 eat genes, mutants in which had abnormal pharyngeal muscle motions, but had normally shaped and normally birefringent pharynxes capable of vigorous contraction. Although the Eat phenotypes were diverse, most resembled those caused by defects in the pharyngeal nervous system. For some of the eat genes there is direct evidence from previous genetic mosaic and pharmacological studies that they do in fact affect nervous system. In eat-5 mutants the motions of the different parts of the pharynx were poorly synchronized. eat-6 and eat-12 mutants failed to relax their pharyngeal muscles properly. These pharyngeal motion defects are most easily explained as resulting from abnormal electrical excitability of the pharyngeal muscle membrane. PMID- 8462850 TI - The mog-1 gene is required for the switch from spermatogenesis to oogenesis in Caenorhabditis elegans. AB - Caenorhabditis elegans hermaphrodites make first sperm, then oocytes. By contrast, animals homozygous for any of six loss-of-function mutations in the gene mog-1 (for masculinization of the germ line) make sperm continuously and do not switch into oogenesis. Therefore, in mog-1 mutants, germ cells that normally would become oocytes are transformed into sperm. By contrast, somatic sexual fates are normal, suggesting that mog-1 plays a germ line-specific role in sex determination. Analyses of double mutants suggest that mog-1 negatively regulates the fem genes and/or fog-1: mog-1; fem and mog-1; fog-1 double mutants all make oocytes rather than sperm. Therefore, we propose that wild-type mog-1 is required in the hermaphrodite germ line for regulation of the switch from spermatogenesis to oogenesis rather than for specification of oogenesis per se. In addition to its role in germline sex determination, maternal mog-1 is required for embryogenesis: most progeny of a mog-1; fem or mog-1; fog-1 mother die as embryos. How might the roles of mog-1 in the sperm/oocyte switch and embryogenesis be linked? Previous work showed that fem-3 is regulated post transcriptionally to achieve the sperm/oocyte switch. We speculate that mog-1 may function in the post-transcriptional regulation of numerous germ-line RNAs, including fem-3. A loss of mog-1 might inappropriately activate fem-3 and thereby abolish the sperm/oocyte switch; its loss might also lead to misregulation of maternal RNAs and thus embryonic death. PMID- 8462851 TI - Molecular characterization of lengthy mitochondrial DNA duplications from the parasitic nematode Romanomermis culicivorax. AB - Complete nucleotide sequences, precise endpoints and coding potential of several 3.0-kilobase mitochondrial DNA (mtDNA) repeating units derived from two isofemale lineages of the mermithid nematode Romanomermis culicivorax have been determined. Endpoint analysis has allowed us to infer deletion and inversion events that most likely generated the present day repeat configuration. Each amplified unit contains the genes for NADH dehydrogenase subunits 3 and 6 (ND3 and ND6), an open reading frame (ORF 1) that represents a cytochrome P450-like gene, and three additional unidentified open reading frames. The primary nucleotide sequences of the R. culicivorax mt-repeat copies within individual haplotypes are highly conserved; three nearly complete copies of the repeat unit vary by 0.01% at the nucleotide level. These observations suggest that concerted evolution mechanisms may be active, resulting in sequence homogenation of these lengthy duplications. PMID- 8462852 TI - Unusual variability of the Drosophila melanogaster ref(2)P protein which controls the multiplication of sigma rhabdovirus. AB - The ref(2)P gene of Drosophila melanogaster was identified by the discovery of two alleles, Po and Pp, respectively, permissive and restrictive for sigma rhabdovirus multiplication. A surprising variability of this gene was first noticed by the observation of size differences between the transcripts of permissive and restrictive alleles. In this paper, another restrictive allele, Pn, clearly distinct from Pp, is described: it exhibits a weaker antiviral effect than Pp and differs from Pp by its molecular structure. Five types of alleles were distinguished on the basis of their molecular structure, as revealed by S1 nuclease analysis of 17 D. melanogaster strains; three alleles were permissive and two restrictive. Comparison of the sequences of four haplotypes revealed numerous point mutations, two deletions (21 and 24 bp) and a complex event involving a 3-bp deletion, all affected the coding region. The unusual variability of the ref(2)P locus was confirmed by the high ratio of amino acid replacements to synonymous mutations (7:1), as compared to that of other genes, such as the Adh (2:42). Nevertheless, nucleotide sequence comparison with the Drosophila erecta ref(2)P gene shows that selective pressures are exerted to maintain the existence of a functional protein. The effects of this high variability on the ref(2)P protein are discussed in relation to its specific antiviral properties and to its function in D. melanogaster, where it is required for male fertility. PMID- 8462853 TI - A genetic analysis of the stoned locus and its interaction with dunce, shibire and Suppressor of stoned variants of Drosophila melanogaster. AB - The genetic complementation patterns of both behavioral and lethal alleles at the stoned locus have been characterized. Mosaic analysis of a stoned lethal allele suggests that stoned functions either in the nervous system or in both the nervous system and musculature, but is not required for gross neural development. The behavioral alleles stnts and stnC, appear to be defective in a diametrically opposite sense, show interallelic complementation, and indicate distinct roles for the stoned gene product in the visual system and in motor coordination. A number of other neurological mutations have been investigated for their possible interaction with the viable stoned alleles. Mutations at two loci, dunce and shibire, act synergistically with the stnts mutations to cause lethality, but fail to interact with stnC. A third variant (Suppressor of stoned) has been identified which can suppress the debilitation associated with the stnts mutations. These data, together with a previously identified interaction between the stnts and tan mutants, indicate a central role for the stoned gene product in neuronal function, and suggests that the stoned gene product interacts, either directly or indirectly, with the neural cAMP second messenger system, with the synaptic membrane recycling pathway via dynamin, and with biogenic amine metabolism. PMID- 8462854 TI - Complex function and expression of Delta during Drosophila oogenesis. AB - Delta (Dl) encodes a cell surface protein that mediates cell-cell interactions central to the specification of a variety of cell fates during embryonic and postembryonic development of Drosophila melanogaster. We find that the Delta protein is expressed intermittently in follicle cells and in germ-line cells during stages 1-10 of oogenesis. Furthermore, Delta expression during oogenesis can be correlated with a number of morphogenetic defects associated with sterility observed in Dl mutant females, including failure of stalk formation within the germarium and subsequent fusion of egg chambers, necrosis in germ-line cells, and multiphasic embryonic arrest of fertilized eggs. We have also identified a Dl mutation that leads to context-dependent defects in Dl function during oogenesis. Direct comparison of Delta protein expression with that of the Notch protein in the ovary reveals substantial, but incomplete, coincidence of expression patterns in space and time. We discuss possible roles for the Delta protein in cell-cell interactions required for cell fate specification processes during oogenesis in light of available developmental and histochemical data. PMID- 8462855 TI - Delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse. AB - Scrapie is a transmissible neurodegenerative disease caused by unusual pathogens called prions. The interval between inoculation and illness for experimental mouse scrapie is dramatically influenced by an incubation time gene (Prn-i) that is linked to Prn-p, the structural gene for prion protein (PrP). Although prion proteins from mouse strains with short and long scrapie incubation times differ by two amino acids, mice with discordant disease phenotype and Prn-p genotype occur in segregating crosses, suggesting recombination between Prn-p and a distinct incubation time locus. In addition, expression of Prn-pb transgenes from long incubation time mice shortened, rather than prolonged, incubation time. In this study, mice carrying chromosomes with meiotic crossovers near Prn-p were analyzed for scrapie incubation time phenotype. The results indicated that Prn-i (should it exist) must lie within an interval 0.67 cM proximal and 0.22 cM distal to Prn-p. The results also suggest that the cumulative effects of other genes, rather than meiotic recombination, were responsible for the putative recombinants of earlier studies. However, the effect of Prn-pb transgene expression in abbreviating scrapie incubation time was mitigated when the transgenes were transferred to mice with an endogenous long incubation time allele. Thus, Prn-pb transgenes and Prn-i may modulate scrapie pathogenesis by different mechanisms. PMID- 8462856 TI - Plastome-genome interactions affect plastid transmission in Oenothera. AB - Plastids of Oenothera, the evening primrose, can be transmitted to the progeny from both parents. In a constant nuclear background, the frequency of biparental plastid transmission is determined by the types of plastid genomes (plastomes) involved in the crosses. In this study, the impact of nuclear genomes on plastid inheritance was analyzed. In general, the transmission efficiency of each plastome correlated strongly with its compatibility with the nuclear genome of the progeny, suggesting that plastome-genome interactions can influence plastid transmission by affecting the efficiency of plastid multiplication after fertilization. Lower frequencies of plastid transmission from the paternal side were observed when the pollen had poor vigor due to an incompatible plastome genome combination, indicating that plastome-genome interactions may also affect the input of plastids at fertilization. Parental traits that affect the process of fertilization can also have an impact on plastid transmission. Crosses using maternal parents with long styles or pollen with relatively low growth capacity resulted in reduced frequencies of paternal plastid transmission. These observations suggest that degeneration of pollen plastids may occur as the time interval between pollination and fertilization is lengthened. PMID- 8462857 TI - Characteristics and mechanisms of nocturnal asthma. AB - Nocturnal worsening of asthma is a very common and significant problem for the vast majority of all asthmatic patients. The involved mechanisms are multiple and interactive. These include circadian alterations in inflammation/mediators, epinephrine, beta 2 receptor function, vagal tone, and body temperature. Other factors may include aspiration, sinusitis, and sleep apnea. Understanding of the mechanisms involved in nocturnal asthma directs the therapeutic approach of these patients. PMID- 8462859 TI - Alternative treatments for severe, chronic asthma. AB - The current focus of treatment for chronic asthma is anti-inflammatory pharmaceuticals and minimizing of environmental factors that contribute to airway inflammation. Despite the development of increasingly potent inhaled glucocorticoids, certain select asthmatic patients require chronic systemic glucocorticoids for management. Several nonglucocorticoid, anti-inflammatory agents have been shown or suggested to be beneficial in the treatment of chronic asthma. The major purpose of using these agents has been to maximize airway function and to minimize the use of systemic glucocorticoids, with their attendant side effects. Some of these alternative anti-inflammatory agents are reviewed in this paper, with emphasis on clinical experience in the treatment of asthma. Additional double-blind, placebo-controlled studies are necessary to define the role of these agents in the management of chronic asthma. PMID- 8462858 TI - Reactions to imported fire ant stings. AB - Reactions to the sting of the imported fire ant are an increasing problem for residents of the Gulf South. Three recent evolutionary changes suggest that the habitat of the ants will continue to expand. This article gives a brief review of the problem, including unresolved questions related to management of sting reactions. PMID- 8462860 TI - Twice-daily peak expiratory flow rate monitoring for the assessment of childhood asthma. AB - The reliability of the home recording of peak expiratory flow rate (PEFR) in 31 newly diagnosed school-aged asthmatic children was monitored. The patients recorded their PEFR values in the morning and at bedtime and filled in their diary cards for 14 days. The mean amplitude of PEFR variation between the highest and lowest daily recordings varied from 1.9 to 34.4% (mean 6.7%) of the daily mean. Seven children, six of whom belonging to the most seriously affected half in the group had two or more daily PEFR variations of 15% or higher, but only two of them had their mean amplitude of variation at that limit or more. When the whole group was considered, however, no significant correlation was found between the mean amplitude of PEFR variation and the symptom score, the medication needed, baseline FEV1/FVC, or the methacholine threshold. The findings indicate that twice-daily PEFR monitoring may help the physician detect some troublesome cases of childhood asthma, but it is of limited value for diagnostic purposes or when assessing the degree of severity of asthma in routine clinical work. PMID- 8462861 TI - Benefits of antibiotic prophylaxis in children with chronic sinusitis: assessment of outcome predictors. AB - Eighty-six children with chronic sinusitis, documented by x-ray with symptoms and signs for more than 12 weeks, were evaluated for atopy and B-cell immune abnormalities. Twenty-nine percent (25/86) of the patients had some B-cell abnormality of immunoglobulin isotype, IgG subclass, and/or hyporesponsiveness to pneumococcal polysaccharide (PPS) vaccine (Pneumovax). Eleven of 17 patients who were hyporesponsive to PPS vaccine had normal immunoglobulin isotypes and IgG subclasses. Twenty-six of these 86 children were followed prospectively for > or = 1 year on prophylactic antibiotics. The 12-month period before the use of prophylactic antibiotics was taken as the control period for each child for comparison. Nineteen of 26 (74%) children had a good outcome (greater than a 50% reduction in the number of exacerbations of sinusitis during a 12-month period compared with the previous year) on prophylactic antibiotics with a reduction in exacerbations of sinusitis from 9.8 per year to 2.7 episodes per year. In contrast, 7/26 had a poor outcome (p < .0001) on prophylactic antibiotics (from 12.6 per year to 8.7 per year on prophylactic antibiotics). There were no significant differences in age, gender, atopy, or presence of a B-cell immune abnormality in the good versus the poor outcome groups to prophylactic antibiotic therapy. Treatment outcome correlated inversely with the number of sinus infections before prophylactic antibiotics, p = .036. Underlying B-cell immune abnormalities could not be correlated with intervention outcome on prophylactic antibiotics. The use of prophylactic antibiotics was an effective treatment modality in children with chronic sinusitis, even in patients with selective immune abnormalities. PMID- 8462862 TI - Mechanisms of inflammation in the asthmatic patient. AB - Our concept of asthma has changed dramatically in the past decade. Although many factors contribute to airflow obstruction in asthma, there is now an expanded focus on all events in bronchial obstruction including bronchospasm, edema, mucous formation, and inflammation. The last of these airway changes, bronchial inflammation, not only causes symptoms of asthma but also contributes or is the cause of a basic characteristic of asthma: airway hyperresponsiveness. It has become apparent that asthma is a complex disease in which the causes of airflow obstruction are multi-factorial, multicellular, and redundant. It is important to identify the cellular mechanisms involved in airway inflammation and to understand how they contribute to changes in airway responsiveness and obstruction. PMID- 8462863 TI - Contribution of the New World food to the world supply. PMID- 8462864 TI - Early Spanish physicians and hospitals in Cuba. AB - Very little is known about the early history of medicine in the Caribbean. Five hundred years ago medicine practitioners from Europe started to settle in the New World. Hospitals were built in very rudimentary houses to care for the sick. Diseases were received and transmitted by the new settlers. The author, a philatelist and a Columbus scholar, uses postage stamps to highlight the introduction of European medicine in Cuba. PMID- 8462865 TI - Spain, Portugal, Christopher Columbus, and the Jewish physician: Part 1. PMID- 8462866 TI - Treatment of nocturnal asthma. AB - Extensive work has been done over the past decade to determine the best drug regimen for the treatment of nocturnal asthma. Much of the work has been directed at the evaluation of theophylline preparations and beta sympathomimetic agents. With a better understanding of the mechanisms causing nocturnal asthma, future therapeutic advances will be targeted at the underlying pathophysiological causes of the disorder. This article will review current treatment modalities, including those shown to have some effect as well as those that have no benefit. PMID- 8462867 TI - Transcriptional control of yeast phosphoglycerate mutase-encoding gene. AB - Yeast genes encoding enzymes of the glycolytic pathway are highly expressed due to transcriptional control elements in their promoters. We provide data on such elements in the 5'-noncoding sequences of the Saccharomyces cerevisiae GPM1 gene, encoding phosphoglycerate mutase. Using fusions to the lacZ reporter gene, a detailed deletion analysis was performed. A palindromic sequence was shown to function as an upstream activation site (UAS) and two upstream repressing sites (URS1 and URS2) were located. Western and Northern blot analyses were used to substantiate the data obtained in enzymatic measurements. The regulatory sequences were shown to be functional in the heterologous CYC1 promoter. In addition, a promoter region was detected which mediated general glycolytic control by the GCR1 regulatory factor. PMID- 8462868 TI - Molecular analysis and overexpression of the gene encoding endothiapepsin, an aspartic protease from Cryphonectria parasitica. AB - The gene, epn-1, encoding endothiapepsin (Epn), an aspartic protease (AspP) synthesized and secreted by the ascomycete fungus responsible for chestnut blight, Cryphonectria (Endothia) parasitica, was identified and characterized. Inspection of the nucleotide and deduced amino acid (aa) sequences revealed perfect agreement with the experimentally derived 330-aa sequence of mature Epn [Barkholt, Eur. J. Biochem. 167 (1987) 327-338] and an additional 89 aa of putative preprosequence. Of the nine fungal AspP characterized to date, Epn was found to be most closely related to aspergillopepsin and penicillopepsin (52% and 55% identity, respectively), proteases produced by the ascomycetes Aspergillus awamori and Penicillium janthinellum, and least related to proteases produced by the yeasts Candida albicans and Saccharomyces cerevisiae (27% and 26% identity, respectively). Epn production was found to be the same in isogenic virus-free and virus-containing strains, indicating that this AspP is not down-regulated by the presence of a hypovirulence-associated viral double-stranded RNA, as has been reported for several other secreted C. parasitica gene products. Strains containing multiple copies of epn-1 were obtained by transformation with a plasmid vector containing the cloned epn-1. One of these strains was shown to produce seven to ten times more Epn than the parental wild-type strain. PMID- 8462869 TI - Sequence analysis suggests a recent duplication of the growth hormone-encoding gene in Tilapia nilotica. AB - The sequence of two growth hormone(GH)-encoding genes from tilapia fish (Tilapia nilotica) is reported. Our data indicate that the presence of two GH in the tilapia genome is a consequence of a relatively recent duplication event. The two genes are highly homologous, having a similar intron (five)/exon (six) arrangement, and both encode an identical polypeptide. Sequence similarity extends up to bp -628 upstream to the transcription start point, after which the sequences of the two genes are not related to each other. The presence of two GH in the tilapia genome is supported both by the nucleotide sequence and by genomic DNA blot hybridization analysis. Tilapias, like salmonids, contain an extra intron compared with the mammalian GH structure. We suggest that within the superorder Teleostei, the insertion of intron 5 into GH took place after the evolutionary separation of Cyprinoidea, but before Isospondyli (salmonids) and Acanthopterygii (tilapias) were separated. Thus, the additional intron which is probably present in many teleost fish GH may provide an excellent natural marker for evolution and classification studies. PMID- 8462870 TI - Structure of rat genes encoding androgen-regulated cystatin-related proteins (CRPs): a new member of the cystatin superfamily. AB - Cystatin-related proteins (CRPs) are abundant androgen-regulated secretory glycoproteins that are specifically synthesized in the ventral prostate and lachrymal gland of the rat. Two complete 6-kb genes, Crp1 and Crp2, have been cloned and characterized. They are differentially expressed and encode slightly different proteins. The genes each contain four exons which are interrupted by large introns. An alignment of their sequences demonstrates an overall homology of 90%. The 3' end of a third gene, Crp3, from which only a 1.5-kb fragment was isolated, displays a sequence identity of 84%. These data indicate the existence of a Crp multigene family. The 5' flanking regions of Crp1 and Crp2 are highly homologous and contain a GATAAA sequence 29 nt upstream from the transcription start point. This TATA-box-like element is also found in the promoters of the genes encoding cystatin type-2 proteins. No other recognizable transcription control elements can be detected. Potential binding sites (ARE) for the androgen receptor are scattered throughout the entire genes. The exon/intron organization of the genes encoding CRPs, the size of the exons and their encoding amino acid sequences exhibiting a characteristic spacing of the Cys residues are structural elements displaying a remarkable similarity with the corresponding elements in the genes encoding cystatin type-2 proteins. CRPs must therefore belong to the cystatin superfamily. However, due to their additional domain encoded in an extra exon 2, CRPs must be classified as a new family, type 5. PMID- 8462871 TI - Promoter region of the rat gene encoding ornithine aminotransferase: transcriptional activity, sequence, and DNase-I-hypersensitive sites. AB - In the rat, the gene (rOAT) encoding ornithine aminotransferase (OAT) is expressed in all cell types examined; however, regulation of rOAT expression is complex and cell-type specific. Various regions of the rOAT 5' flanking domain were cloned upstream from the cat reporter gene, and the expression of these OAT::cat fusions was examined following transfection into rat kidney epithelial cells (NRK-52E), human embryonic kidney cells (293), and rat hepatoma cells (H-4 II-E). Although these experiments suggested the presence of one or more positive regulatory elements between nucleotides -661 and -158, and one or more negative elements upstream from nt -897, none of these putative elements appeared to function in a cell-type-specific manner. The nt sequence of 2531 bp of the rOAT domain flanking the promoter revealed several putative promoter/enhancer elements in positions analogous to the human OAT gene, numerous AGGTCA-like motifs related to the binding sites for the estrogen and thyroid hormone receptors, and multiple motifs resembling a putative regulatory element associated with genes encoding enzymes of the urea cycle. Finally, sensitivity of the 5' end of rOAT to cleavage by DNase I was examined, as DNase-I-hypersensitive sites (DHS) are often found in association with cis-acting regulatory elements. Two DHS were identified; one DHS approximately 140 bp upstream, and the second DHS approximately 300 bp downstream, of the transcription start point (tsp). These data provide the foundation upon which to base future studies aimed at elucidating the molecular mechanisms through which rOAT expression is regulated in a cell-type specific manner. PMID- 8462873 TI - Isolation and characterization of the Aspergillus oryzae gene encoding aspergillopepsin O. AB - We have cloned and determined the nucleotide sequence of a genomic DNA segment from Aspergillus oryzae which contains pepO, the gene encoding the aspartic proteinase, aspergillopepsin O (PEPO). The organization of pepO is strikingly similar to that of pepA from A. niger var. awamori (previously called A. awamori) in that both are composed of four exons and three introns with virtually identical lengths, and the positions of the introns are exactly conserved. From the deduced amino acid (aa) sequence, it appears that PEPO, like other fungal aspartic proteinases, is synthesized as a zymogen containing a putative N terminal prepro-region of 77 aa followed by a mature protein of 327 aa. Southern blotting experiments suggest that a single copy of pepO exists in the A. oryzae genome. PMID- 8462872 TI - Sequence of the Schizosaccharomyces pombe gtp1 gene and identification of a novel family of putative GTP-binding proteins. AB - A new gene, gtp1, has been identified by sequence analysis in Schizosaccharomyces pombe. The open reading frame was identified downstream from the stf1 locus. The deduced GTP1 protein has strong sequence similarity to a family of putative GTP binding proteins from Halobacterium cutirubrum, Bacillus subtilis, Drosophila melanogaster and mouse. The conserved P-loop phosphate-binding motif places gtp1 in a family separate from previously described groups of such proteins. PMID- 8462874 TI - Hidden domains and active site residues in beta-glycanase-encoding gene sequences? AB - Reading-frame corrective shifts in the nucleotide sequence upstream, within, or downstream from the putative coding region of several beta-glycanase-encoding genes reported in the literature reveal hidden active-site residues or even additional domains, including a cellulose-binding domain on a beta-mannanase encoding gene. These findings also help in assigning, to cellulase family A, two enzymes previously found to lack sequence similarity with known cellulase families. PMID- 8462875 TI - The Drosophila melanogaster developmental gene g1 encodes a variant zinc-finger motif protein. AB - In Drosophila melanogaster, the mechanisms involved in the pattern formation of complex internal organs are still largely unknown. However, the identity of the molecular determinants that control the development of these specific tissues is emerging from the combined use of genetic and molecular approaches. We have cloned a gene that is expressed in the mesoderm, one of the fundamental embryonic germ layers which gives rise to internal structures, such as the musculature. Here, we describe the molecular characterization of this gene, designated as g1. The nucleotide (nt) sequence of its cDNA shows an open reading frame of 852 nt, which encodes a 32-kDa protein with two putative zinc fingers, and a serine/glutamine/proline-rich region. These features indicate a functional role for g1, which remains to be elucidated, in regulating gene expression during mesoderm formation. PMID- 8462876 TI - Characterization of the 130-bp repeat enhancer element of the rat ribosomal gene: functional interaction with transcription factor E1BF. AB - The 130-bp repetitive element (RE) of the rat rDNA (ribosomal RNA-encoding gene) intergenic spacer stimulated the synthesis of rRNA four- to sixfold, in comparison with that of the promoter alone, both in vivo and in vitro, when ligated to the rat rDNA promoter. The addition of increasing amounts of highly purified E1BF (enhancer-1 binding factor), which binds to the rat rDNA promoter and an upstream nonrepetitive enhancer element [Zhang and Jacob, Mol. Cell. Biol. 10 (1990) 5177-5186], to an in vitro transcription system resulted in enhancement of rDNA transcription from the recombinant plasmids containing the promoter or promoter-RE. However, E1BF-mediated stimulation of transcription under the influence of the RE continued at higher concentrations of E1BF than did the control transcription from the promoter alone. The binding affinity of E1BF for the RE was comparable to its affinity for the nonrepetitive far upstream enhancer element previously characterized in our laboratory. The sequences protected by E1BF in the RE differed from those protected by UBF (upstream control element binding factor), a well characterized pol I transcription factor. These data suggest that E1BF belongs to a class of transcription factors which interact with the promoter and spacer cis-acting RE to modulate rDNA transcription. PMID- 8462877 TI - Cytoplasmic and periplasmic production of human apolipoprotein E in Escherichia coli using natural and bacterial signal peptides. AB - To understand the toxicity of high levels of heterologous human serum apolipoprotein E (ApoE) in Escherichia coli, as well as to prepare a system for producing the structural domains of this protein, plasmids were constructed in which the coding sequence of the N-terminal domain or all of ApoE followed E. coli or human apolipoprotein signal peptides (SP) or the N-terminal eleven amino acids (f10) of the gene 10-encoded protein of phage T7. High levels of production of the 22-kDa N-terminal domain (22K) of ApoE were obtained either as an f10::22K fusion protein, or using the natural SP, or SP derived from the periplasmic protein, alkaline phosphatase (PhoA), or from the outer membrane protein A (OmpA). Microsequencing showed that the SP of sPhoA::22K and sOmpA::22K, but not sApoE::22K, were correctly processed and, in the former cases, the protein could be released from the cells by osmotic shock. The extent of maturation of sPhoA::22K depended upon the host strain; with JM109, about 50% of the protein was not processed. Microsequencing of the f10::22K fusion protein, which could easily be purified following lysis of the cells, showed that the N-terminal methionine had been removed in agreement with the length parameter rule. Although considerable levels of the f10::ApoE fusion protein could be produced in the cytoplasm, production was markedly less using the PhoA signal peptide and the protein was not easily isolated following osmotic shock. The recombinant protein was biologically active after reconstitution with lipids in spite of the N terminal modifications introduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8462878 TI - A human genome YAC library in a selectable high-copy-number vector. AB - An experimental yeast artificial chromosome (YAC) library consisting of one genome equivalent of human DNA was prepared in a selectable high-copy-number (hcn) YAC vector. Screening for unique loci was accomplished by PCR of successively smaller DNA pools and by hybridization to high-density microcolony blots. Inserts averaged 200 kb in size, but several YACs with inserts averaging about 650 kb were obtained when polyamines were added prior to yeast transformation. YACs were identified for 17 out of 29 sequence-tagged sites (STS) screened by a PCR-based approach. All YACs in the size range of 100-600 kb that were examined could be obtained at significantly elevated copy numbers following growth of the clones in methotrexate/sulfanilamide/thymidine-supplemented medium. The hcn YACs could also be selected during growth in microtiter dishes, and the resulting clones were used to prepare high-density microcolony DNA blots for hybridization with radiolabeled PCR products. DNA pools for the PCR-based screening of this experimental library are available to investigators interested in applications of hcn YACs. PMID- 8462879 TI - Nucleotide sequence of a ras gene from the basidiomycete Coprinus cinereus. AB - The basidiomycete Lentinus edodes (Le.) ras gene (or its cDNA clone) [Hori et al., Gene 105 (1991) 91-96] was utilized to identify and clone the corresponding gene (Cc.ras)-containing genomic fragment from the basidiomycete, Coprinus cinereus. Cc.ras encodes 215 amino acids (aa) interrupted by six small introns. The deduced Cc.RAS protein exhibits significant homology (84.7% identical) to the Le.RAS protein (217 aa) in size and aa sequence. PMID- 8462880 TI - Sequence of the goat alpha s2-casein-encoding cDNA. PMID- 8462881 TI - Hospitals: danger zone of the '90s. PMID- 8462882 TI - Common skin disorders of aging: diagnosis and treatment. AB - The incidence of skin disorders increases with age because of changes in skin structures and a lifetime accumulation of environmental insults. Photoaging, resulting from exposure to harmful ultraviolet wavelengths in sunlight, is responsible for many common skin disorders, from wrinkles to melanoma. Older patients also see their physicians with complaints of various types of dermatitis, including contact and seborrheic. Although skin disorders vary in severity, they all adversely affect an older patient's health and/or quality of life. Early recognition, prevention, and treatment of skin diseases by the primary care physician is therefore an important element in the overall care of the middle-aged and older patient. PMID- 8462883 TI - Hypertension: patient evaluation, indications for treatment. AB - Hypertension in older adults is a prevalent problem with significant morbid consequences, including cerebrovascular, cardiac, and renal disease. Recent studies have established a firm rationale for drug therapy in this population, and therapeutic developments have made effective treatment possible. Patient evaluation includes searches for secondary causes, risk factors for cardiovascular disease, and comorbidity. Antihypertensive therapy requires lifestyle interventions aimed at addressing overall cardiovascular risk factors. Drug therapy decisions are based on level of hypertension, side effects, and comorbid conditions. Older patients can be treated safely and effectively with any of the available antihypertensive agents, but drug selection should be individualized. PMID- 8462884 TI - Common blood disorders: a primary care approach. AB - Many anemias and diseases of the blood-forming elements increase in incidence with advancing age. Iron deficiency remains the cause of most cases of anemia and may be related to inapparent blood loss. Other responsive anemias that can be managed by the primary care physician include vitamin B12 and folate deficiencies and drug- or autoimmune-related hemolytic anemia. Nonresponsive anemias, including hematologic malignancies, are quite common in older patients and require referral to a specialist. Platelet disorders are often produced by certain drugs and, like most refractory anemias, often require a bone marrow aspirate for diagnosis. PMID- 8462885 TI - Blood-retinal barrier permeability and its relation to progression of retinopathy in patients with type 2 diabetes. A four-year follow-up study. AB - Forty patients with late-onset diabetes (age at diagnosis 30 years or more) and minimal retinopathy as found by fundus photography were followed prospectively by repeated examination (baseline, 1 year, and 4 years). The study shows that early retinopathy changes are not permanent or invariably progressive. In the 1st year of follow-up microaneurysms worsened in 25%, improved in 10%, and remained stabilized in 65%. Vitreous fluorometry was able to detect an overall increase of 0.84 +/- 1.06 x 10(-6) min-1 in blood-retinal barrier (BRB) penetration ratios. After 4 years, 16 of the 40 patients had undergone photocoagulation (focal photo coagulation in 11 and pan retinal photocoagulation in 5). The eyes that needed photocoagulation were the eyes that had higher fluorometry penetration ratios at the patient's entry into the study and showed a higher rate of deterioration during the 1st year of the study (5.54 +/- 1.97 vs 3.11 +/- 1.22 x 10(-6) min-1, P < 0.001, initial values; 1.52 +/- 0.76 vs 0.45 +/- 0.99 x 10(-6) min-1, P < 0.001, annual increase in leakage). The eyes that did not need photocoagulation, 24 out of 40, showed stable fluorometry readings within the 4-year period of follow-up (+0.02 +/- 0.98 10(-6) min-1). Abnormally high vitreous fluorometry values and their rapid increase over time appear to be good indicators of rapid progression and worsening of the retinopathy. PMID- 8462886 TI - Correlation of spatial contrast sensitivity and visual fields in glaucoma. AB - Perimetry is the standard examination in glaucoma, whereas contrast sensitivity is often proposed as a complementary test. This study investigates the extent to which the outcomes of the two tests correlate. One eye each of 44 glaucoma patients and 16 glaucoma suspects was tested with the Haag-Streit Visometer and the Octopus 201 perimeter (program G1). Contrast sensitivities correlated highest with the center of the visual field (Spearman's rho = 0.76; P < 0.001) and slightly less with the mean sensitivity of the entire visual field (rho = 0.63; P < 0.001). Mean contrast sensitivity correlated weakly with the square root of corrected loss variance (rho = -0.45; P < 0.001) and short-term fluctuation (rho = -0.34; P < 0.007). The two tests differed considerably only in very few patients. We recommend careful evaluation of the central area of glaucomatous visual fields whenever contrast sensitivity testing is not available. PMID- 8462887 TI - The progression of retinopathy of prematurity and fluctuation in blood gas tension. AB - In this study, the relationship between the fluctuation in blood oxygen and carbon dioxide tension and the progression of acute retinopathy of prematurity (ROP) was evaluated. Eighteen extremely premature infants were selected on the basis of the following criteria: gestational age less than 26 weeks, oxygen supply or mechanical ventilation for more than 50 days, transcutaneous oxygen pressure (TcPO2) recorded almost once per hour, and arterial oxygen pressure (PaO2) and arterial carbon dioxide pressure (PaCO2) measured intermittently, for over 8 weeks after birth. All of these infants developed ROP, which ceased progressing in 7 infants (group I, stage 1 or 2 ROP, international classification), but advanced in 11 (group II, stage 3 or 3+). The fluctuations in TcPO2, PaO2, and PaCO2 are represented as coefficients of both variation (CV) and mean difference (D) in these two groups. The results demonstrate that both the CV and D values of TcPO2 are significantly elevated in group II infants compared with group I infants, in the first and second 3-weeks periods, and over the entire 9-week period after birth. The incidences of extreme hyperoxemia (TcPO2 > or = 100 mm Hg) and hypoxemia (TcPO2 < 30 mm Hg) in recorded TcPO2 time series show no significant differences between these two groups. We conclude that extremely premature infants with widely fluctuating arterial oxygen tension may have a greater chance of developing progressive ROP. PMID- 8462888 TI - Sodium hyaluronate 0.25% used as a vehicle increases the bioavailability of topically administered gentamicin. AB - Sodium hyaluronate (SH) solutions have a longer precorneal residence time than isotonic saline solution in rabbits and in humans. The present study investigates the effect of a 0.25% SH vehicle, compared with a phosphate buffer solution (PBS), on the tear concentration after topical administration of gentamicin sulfate (GS) in humans. Eight volunteers received 25 microliters 0.5% GS in PBS in the left eye and 25 microliters 0.5% GS in 0.25% SH in the right eye. Tear samples of 1 microliters were taken from the inferior sulcus using a capillary before instillation and 5, 10, 20, and 40 min after instillation. The tear concentration of GS was determined by radioimmunoassay. There was a statistically significantly higher concentration of GS in the inferior conjunctival sulcus of the SH-instilled eye at 5 min (P < 0.01) and at 10 min (P < 0.05) after instillation (paired t-test, n = 9). At 20 min the concentration of GS in the SH instilled eye was only slightly higher, and at 40 min GS concentrations in left and right eyes were comparable. SH 0.25% used as a vehicle therefore increases the availability of GS at the ocular surface for at least 10 min. This effect could be due to the prolonged precorneal residence time of SH. PMID- 8462889 TI - Clinical and immunohistochemical correlation of herpetic keratitis with the expression of HLA-DR antigen. AB - The corneal buttons after corneal graft of 22 patients with herpetic keratitis were studied (16 male, 6 female; 7-87 years of age). Ten still had active inflammation, while 12 had stabilized by the time of the study. Different degrees of neovascularization were observed in 19 cases. HLA-DR antigen was detected in the corneal epithelium in 7 of 22 cases (32%), in the corneal stroma in 17 of 22 cases (77%), and in the endothelium in 9 cases (41%) by using the immunohistochemical technique. The expression of HLA-DR antigen was more common and more marked in active herpetic keratitis (90%) and in neovascularized corneas (84%). The frequency and density of HLA-DR expression in perforating corneal ulcers were no higher than in other cases, but anterior synechia was accompanied by strong expression of HLA-DR antigen in the corneas. The expression of HLA-DR antigen was not only detected in the peripheral, but also in the central area of the specimens. The cells expressing HLA-DR antigen in corneas were mainly corneal cells. The results showed a close relationship between HSV-keratitis and the expression of HLA-DR antigen, which may be induced during the clinical course of the disease. The expression of HLA-DR might be one of the factors in the recurrent onset of the disease and a significant sign of the prognosis of corneal transplantation for these patients. PMID- 8462890 TI - Chronic granulomatous anterior uveitis associated with multiple sclerosis. AB - A retrospective review is presented of the medical records of seven female patients with uveitis associated with definite multiple sclerosis. Six of the patients had severe bilateral chronic granulomatous anterior uveitis, which in four cases resulted in extensive posterior synechiae and scarring of the peripupillary iris. One patient had bilateral intermediate uveitis with unilateral posterior synechiae. Severe chronic granulomatous anterior uveitis associated with multiple sclerosis has a predilection for women, can precede neurological symptoms and can be controlled with topical steroids. PMID- 8462891 TI - A morphometric and stereologic analysis of ganglion cells of the central human retina. AB - Unbiased estimates of the cell density of the ganglion cell layer (GCL) were made by the Disector method, and the topography of the nerve fibre layer (NFL) between the centre of the fovea and the optic disc was studied, in human retina under both normal and pathological conditions. Three human retinae were examined, the eyes having been removed in the course of cancer surgery. Before operation two of the patients had visual acuity within normal limits. The third patient had impaired vision. In the two normal retinae, the cell densities of the GCL in the foveal wall were approximately 60,000/mm2. Estimates were also made outside the fovea and these showed a progressive reduction in cell density from the foveal wall towards the optic disc. The NFL simultaneously increased in thickness to approximately 70-100 microns at the peripapillary border. At 4 deg eccentricity nasal to the fovea the majority of axons had a mean diameter of less than 0.42 microns. Closer to the optic disc, the number of large axons increased in the inner parts of the NFL. In the third eye with long- and short-term visual impairment there was a substantial cell loss in the GCL, with only some 15,000 cells/mm2 in the foveal wall. In spite of cell/axon loss the thickness of the NFL was increased due to axonal swelling. PMID- 8462892 TI - Immunohistochemical detection of blood-retinal barrier breakdown in streptozotocin-diabetic rats. AB - Immunohistochemical staining for albumin (69 kDa) and fibrinogen (340 kDa), as markers of blood-retinal barrier (BRB) breakdown of the retinas of streptozotocin treated diabetic rats, was performed. The number of rats with BRB breakdown was three of nine at 6 months, four of seven at 12 months, and three of three at 18 months. Extravasation of albumin from the retinal vessels was detected in the retinas of rats maintained for 6, 12, and 18 months, while extravasation of fibrinogen was detected only in the retinas of rats maintained for 18 months. These findings suggested that the duration of diabetes has an influence on BRB breakdown and that each substance in the blood starts to permeate the vascular wall individually. PMID- 8462893 TI - New sites of ocular involvement in late-infantile metachromatic leukodystrophy revealed by histopathologic studies. PMID- 8462894 TI - The British Society of Gastroenterology, spring meeting. 24-26 March 1993. Abstracts. PMID- 8462895 TI - Challenges in immunoscintigraphy of ovarian cancer. PMID- 8462896 TI - Clinical assessment of 111In-CYT-103 immunoscintigraphy in ovarian cancer. AB - The ability of 111In-CYT-103 immunoscintigraphy to aid in the diagnosis of patients with primary or recurrent/residual ovarian cancer was evaluated in a multicenter trial. The 111In-labeled immunoconjugate of the monoclonal antibody B72.3 was prepared using a site-specific conjugation method. A total of 103 patients received a 1 mg infusion of 111In-CYT-103 and subsequently underwent surgery or biopsy. The infusion of 111In-CYT-103 was well tolerated; only 1 patient experienced a modest elevation in blood pressure that was likely related to the infusion. 111In-CYT-103 immunoscintigraphy correctly identified surgically confirmed tumor in 68% of patients with ovarian adenocarcinoma. The sensitivity of 111In-CYT-103 immunoscintigraphy was positively influenced both by the size of the tumor lesion and the tumor TAG-72 antigen expression. The overall sensitivity of 111In-CYT-103 immunoscintigraphy was greater than that of CT imaging (44%). Antibody imaging detected occult disease in 20 of 71 patients with surgically documented ovarian adenocarcinoma; 6 patients being evaluated after initial surgery and chemotherapy had an otherwise negative presurgical workup and a normal CA 125 serum level. The results of this trial also indicate that 111In-CYT 103 immunoscintigraphy can contribute to the medical and surgical management of some patients with ovarian cancer. The results of this trial indicate that 111In CYT-103 immunoscintigraphy should be a valuable addition to the presurgical evaluation of patients with suspected persistent or recurrent ovarian cancer. PMID- 8462897 TI - The gynecologist and multiple organ failure syndrome (MOFS). AB - Multiple organ failure syndrome (MOFS) has been alluded to since the early 1940s. It was recognized as a progressive failure to organs in the mid 1970s. Mortality from this syndrome increases proportionally, as the number of failed organs increases. Therapies to prevent MOFS and current concepts about treating failures of individual organs will be presented. Data sources were retrieved from critical care and surgical literature using MEDLINE from 1966 to the present. Searches were confined to English. Several promoters of MOFS are related to the care of gynecologic patients, especially sepsis and hemorrhage. Treatment strategies, especially those related to pulmonary, gastrointestinal, renal, cardiovascular, and nutritional aspects are discussed. Outcome and prognosis may be affected if recognition and therapeutic intervention are initiated early in the clinical course. The ability to prognosticate outcome is related to the number of organs involved. Gynecologists should have clear knowledge of the prognosis of progressive organ failure in order to appropriately counsel the patient and her family. PMID- 8462898 TI - Lymphocytes isolated from the peritoneal fluid of women with advanced ovarian carcinoma differ significantly from autologous peripheral blood lymphocytes. AB - The phenotypic and functional analysis of ovarian carcinoma-associated lymphocytes (OCAL), obtained from a group of patients with neoplastic carcinosis, reveals major differences between OCAL and peripheral blood lymphocytes (PBL). Virtually all of the OCAL belong to the T cell lineage, whereas both B and natural killer (NK) cells are virtually absent. NK activity is also significantly lower than that exerted by PBL. Following treatment with rIL-2, lymphokine activated killer cell activity is poorly inducible in OCAL. In addition, in vitro stimulated OCAL produce low amounts of lymphokines. Clonal analyses reveal a low clonal efficiency, which indicates a severe proliferative defect. T cell clones obtained show peculiar features: the percentage of CD4 and CD8 clones varies greatly in the different samples. Both CD8 and a significant proportion of proliferating CD4+ clones are cytotoxic in a lectin-dependent cytolytic assay. These findings, together with the results obtained from comparative analyses of the peripheral blood of the same group of patients, demonstrate the unique characteristics of OCAL and should be considered in the preparation of protocols for the locoregional immunotherapy of ovarian carcinoma. PMID- 8462899 TI - Expression of alpha-smooth muscle actin in benign or malignant ovarian tumors. AB - We compared the expression of alpha-smooth muscle actin (alpha-SMA) between benign and malignant human ovarian tissues by immunohistochemical staining and Western blot analysis using the monoclonal antibody specific to alpha-SMA. In normal human ovaries, alpha-SMA was found in the blood vessel walls, muscle fibers, and stromal cells surrounding the follicles. The main source of alpha-SMA in the benign ovarian tumors was the blood vessel walls which highly expressed the alpha-SMA throughout the tumor. In malignant tumor tissues, however, the vessels located in or close to the cluster of cancer cells did not express alpha SMA. It corresponded to the results of the Western blot analysis, showing that the amount of alpha-SMA in malignant ovarian tumor tissues was much smaller than that in benign tumor tissues. Thus, the alteration in alpha-SMA expression seems to reflect the qualitative difference in vessels between benign and malignant ovarian tissues, and therefore alpha-SMA is considered to potentially be a histopathologically useful marker for indicating the malignant potential of ovarian tumors. PMID- 8462900 TI - Solitary recurrent metastasis of epithelial ovarian cancer in the spleen. AB - In epithelial ovarian cancer, solitary metastasis to and recurrences in the parenchyma of the spleen are rare in the absence of apparent disease in other sites. We report four patients who developed isolated, solitary splenic parenchymal recurrences of their epithelial ovarian adenocarcinomas and underwent a splenectomy to remove the recurrent disease. They had undergone optimal cytoreductive surgery for stage III grades 2-3 serous cystadenocarcinoma of the ovary, followed by six to nine cycles of cisplatin and cyclophosphamide chemotherapy and a negative second-look laparotomy. Evidence of relapse developed 2, 4, 6, and 10 years after initial treatment. In two patients, a rising CA-125 heralded the recurrence that was subsequently documented by computed tomography (CT) of the abdomen and pelvis with a single defect noted only in the splenic parenchyma. Two others had only a defect on CT scan. Based on these findings, the otherwise healthy women underwent an exploratory laparotomy, each had a single focus of recurrent poorly differentiated disease that was found in the splenic parenchyma and a splenectomy was performed. Multiple biopsies and cytologies revealed no other evidence of microscopic disease. There was no major postoperative morbidity. Subsequently, one woman was treated with intraperitoneal cisplatin, two with intravenous carboplatin, and one declined further therapy. Three women are alive and free of disease at 6 months to 3 years. The fourth woman is alive with recurrent disease near the site of the resected spleen found 10 months postsplenectomy. Thus, splenic recurrence of epithelial ovarian cancer can occur in the absence of other demonstrable metastasis, and it can be preceded by elevation of CA-125 and an abnormal CT scan. Based on this limited experience with selected patients, splenectomy may have a role in the management of this unusual recurrence. PMID- 8462901 TI - Skin metastasis from carcinoma of the uterine cervix. AB - Of 1190 patients with carcinoma of the uterine cervix, 15 (1.3%) developed skin metastases. The incidence of skin metastasis was 0.8% in stage I, 1.2% in stage II, 1.2% in stage III, and 4.8% in stage IV. The incidence of skin metastasis seemed to be higher in patients with adenocarcinoma and undifferentiated carcinoma than in patients with squamous cell carcinoma. The interval between the diagnoses of cervical cancer and skin metastasis ranged from 0 to 69 months, with a mean of 16.9 months. The most common sites of skin lesions were the abdominal wall and vulva, followed by the anterior chest wall. Skin lesions presented as nodules in 86.7% (13/15), and 66.7% of the patients had multiple lesions. Skin metastasis was detected as the initial metastatic lesion in 9 patients. However, only 4 patients had neither local recurrence nor other distant metastasis at the time of diagnosis of skin metastasis. The prognosis was grave, but 3 patients survived more than 12 months after the diagnosis of skin metastasis. The main treatment for these patients was extirpation of the skin lesion followed by radiotherapy. PMID- 8462902 TI - Radical hysterectomy for stage IB adenocarcinoma of the cervix: the University of Miami experience. AB - The treatment of adenocarcinoma of the cervix has traditionally followed that of squamous cancer. A 25-year review of 88 radical hysterectomies for Stage IB adenocarcinoma of the cervix at the University of Miami/Jackson Medical Center (UM) is compared to over 1600 cases reported in the literature. Adenocarcinoma represented 10.4% of 978 radical hysterectomies performed at UM from July 1965 to December 1990. In a survey of the literature, patients with Stage IB cervical adenocarcinoma treated by radical surgery alone had a statistically better 5-year survival than those treated by radiation alone (79% vs 67%, respectively; P < or = 0.05). Furthermore, no additional benefit was achieved by combining the two therapeutic modalities. The corrected 5-year survival at UM is 81% for Stage IB adenocarcinoma of the cervix treated with radical hysterectomy, a number consistent with the cumulative data base. Radical surgery is an acceptable primary therapy in Stage IB adenocarcinoma of the cervix. PMID- 8462903 TI - Immunohistochemical staining for CA-125 in fallopian tube carcinomas. AB - From 1981-1991, 15 patients with primary fallopian tube carcinomas were treated at the University of Kentucky Medical Center. Immunohistochemical staining for CA 125 was performed on tumor specimens from all cases. Thirteen tumors (87%) stained positively for CA-125. Antigen staining was most intense in the apical portions of carcinoma cells. Serum CA-125 levels were measured in 5 patients and were elevated in 4 (80%). There was a positive correlation between tumor and serum antigen expression in these cases. Serum CA-125 levels accurately reflected disease status in the patients studied. These data suggest that CA-125 is a useful marker in patients with fallopian tube carcinoma. Immunohistochemical localization of CA-125 in tumor tissue should predict which patients will benefit most from serial antigen determinations. PMID- 8462904 TI - Primary leiomyosarcoma of the ovary in a perimenarchal female. AB - A case of primary leiomyosarcoma of the ovary in a perimenarchal female is presented. Previous to this report, ovarian leiomyosarcoma was thought to arise predominantly in postmenopausal women and, indeed, this is the first reported case in a pubertal adolescent. The sarcoma was associated with bilateral cellular ovarian leiomyomas, suggesting malignant degeneration of such tumors. After complete resection, the patient is alive without evidence of recurrent disease 20 months after diagnosis. A review of the literature suggests that chemoradiation is of unproven benefit and aggressive surgical management is recommended. PMID- 8462905 TI - Venous air embolism through a Groshong catheter. AB - Individuals with cancer frequently require long-term central venous access to deliver chemotherapy, blood products, and other fluids. A rare, but potentially lethal complication associated with central venous catheterization is venous air embolism which occurs most commonly after damage or disconnection at the catheter hub. The Groshong (Bard Access Systems, UT) catheter is a device with a unique three-position valve at its distal tip which eliminates the need for routine heparin flushing and minimizes the risk of venous air embolism. This report describes for the first time a near fatal venous air embolism in a patient with an externally accessed Groshong catheter. PMID- 8462906 TI - Primary ovarian melanoma arising in a dermoid stage IIIc: long-term disease-free survival with aggressive surgery and platinum therapy. AB - A 20-year-old female with a primary melanoma of the ovary arising from a mature cystic teratoma presented with bulky peritoneal metastases. Following aggressive surgical resection and platinum-based chemotherapy the patient remains disease free 5 years following diagnosis. PMID- 8462907 TI - Endodermal sinus tumor of the vagina in an infant: magnetic resonance imaging evaluation. AB - Endodermal sinus tumor is a rare and highly malignant lesion. This report documents the clinical findings and magnetic resonance imaging (MRI) of an uncommon case of the endodermal sinus tumor arising in the vagina of a 6-month old infant. MRI was extremely accurate in delineating the possible extent and location of the vaginal lesion. This is the first report to demonstrate MRI of vaginal endodermal sinus tumor. PMID- 8462908 TI - Cryosurgery for cervical intraepithelial neoplasia: 10-year follow-up. PMID- 8462909 TI - Monitoring CA 125 serum levels during early chemotherapy is an excellent prognostic method in advanced ovarian cancer. PMID- 8462910 TI - [Current diagnosis of Crohn disease and ulcerative colitis]. PMID- 8462911 TI - [Therapy of chronic hepatitis B, C and D with alpha-interferon]. PMID- 8462912 TI - [Diagnosis in general practice. Part 6: Shoulder-arm pain]. PMID- 8462913 TI - [A layered lattice antacid with long-term effectiveness. Profile of action and safety exemplified by magaldrate]. PMID- 8462914 TI - [Fracture management in elderly patients. A technically and ethically challenging responsibility]. AB - The accident surgeon is increasingly being confronted with typical fractures of old age. These differ from those seen in other phases of life in that they characteristically occur in a situation of reduced mental performance, and coordination, and are associated with structural bone weakness. Also typical is the fact that there is usually no external causal factor involved. Many patients are polymorbid. Treatment of lower-limb fractures concentrates on early re mobilization. Uncontrolled full weight bearing cannot be avoided, and medullary nailing is therefore preferable to plating. In the case of comminuted fracture of the humerus head or medial femoral head fractures, the chances of reconstruction with preservation of bone vitality are poor and the use of an endoprosthesis permits early functional recovery. Rehabilitation facilities tailored to the needs of elderly trauma patients are required. In the acute trauma unit, the increasing demands being made by geriatric trauma care make staff and structural changes necessary. PMID- 8462915 TI - [Thoracic surgery in advanced age. Indications and results with special reference to bronchial cancer]. AB - BACKGROUND: As the life expectancy in the general population increases, a constant rise in the number of patients of advanced age undergoing thoracic surgery is also observed. MAJOR TOPICS DISCUSSED: Among the indications for operations on the chest, malignant diseases head the list. Thanks to advances in anesthesia, intensive care and surgical techniques, the peri-operative mortality rate in this age group has been appreciably reduced in recent years. In our own patient material, the relevant figure was 4.37%, and is thus in the lower range of internationally comparable mortality associated with major oncological operations on the chest. CONCLUSION: Patients in their seventies or eighties should not be denied thoracic surgery for age reasons; the decisive factors are the general level of activity of the patient and his/her motivation. PMID- 8462916 TI - [New guidelines for fracture treatment. Part 7: Ambulatory after care of fractures--course of healing]. PMID- 8462917 TI - [Treatment of chronic diarrhea in Crohn disease. A pilot study of the clinical effect of tannin albuminate and ethacridine lactate]. AB - METHOD: The present prospective controlled study investigated the effect of a combination of 500 mg of tannin albuminate and 50 mg ethacridine lactate (Tannacomp) on chronic diarrhea in stable-phase Crohn's disease. Of the 30 patients admitted to the study, Crohn's disease was confined to the small intestine in 5, involved both small and large bowel in 11 patients, and only the large intestine in 14 cases. TREATMENT: Basic treatment was continued throughout the study; in addition, three times 2 tablets of Tannacomp were administered for 5 days, followed by a 5-day period of no such treatment, and then a further 5 days with the same regimen. RESULTS: At the end of the treatment phases, there was a significant reduction in stool frequency from 5.5 +/- 0.6 (mean +/- SEM) to 4.0 +/- 0.8, and the summed score of the symptoms decreased from 6.3 +/- 0.6 to 5.3 +/- 0.6; in comparison with the initial situation or at the end of the five day period of no additional treatment, the consistency of the stools also increased. The effect of Tannacomp showed a tendency to be more marked among patients with Crohn's disease limited to the large intestine, as compared with patients with small intestinal involvement. However, before Tannacomp can be recommended as treatment of chronic diarrhea in stable-phase Crohn's disease, further studies are needed. PMID- 8462918 TI - [Therapy of aspergillus infection in AIDS]. PMID- 8462919 TI - [Hepatitis B in obstetrics is serious! E. Petersen, Freiburg, on transmission of HBV infection. Interview by Elisabeth B. Moosmann]. PMID- 8462920 TI - Non-parasitic liver cysts and polycystic liver disease: results of surgical treatment. AB - The results of surgical treatment in 8 patients with polycystic liver disease (group A) and 6 patients with symptomatic simple cysts (group B) are presented. In group A, all patients underwent hepatic resection, in some cases combined with deroofing or fenestration procedures. Complications occurred postoperatively in 3 patients (37.5%). Two of these three patients had no perceived benefit from the surgical treatment. Two other patients had recurrent symptoms 12 and 20 months after operation, and one patient underwent a second resection after a 5-year interval; she is now symptom-free after 19 months of follow-up. In group B, no complications occurred after surgical treatment consisting of either deroofing or pericystectomy. These patients were symptom-free after 5-32 months of follow-up. The therapeutic management of non-parasitic cystic liver disease is still under discussion. We advocate wide deroofing or pericystectomy for symptomatic simple cysts. Hepatic resection in highly symptomatic polycystic disease is surgically demanding and should be performed by an experienced liver surgeon. Relief of symptoms can be achieved, but the rate of complications is relatively high. PMID- 8462921 TI - Liver resection and intractable postoperative ascites. AB - Among 211 patients who, between 1985 and 1990, underwent liver resection in Kyushu University Hospital, uncontrollable ascites occurred in 53 (25%). A univariate analysis revealed that postoperative death with liver failure occurred more frequently in patients with intractable ascites (p < 0.05). Alanine amino transferase levels were significantly higher in patients with intractable ascites (p < 0.05), but serum bilirubin, alkaline phosphatase and serum albumin levels did not differ significantly. Portal pressure (p < 0.05), the operation time (p < 0.01) and blood loss (p < 0.01) were significantly higher in patients with intractable postoperative ascites. A multiple analysis showed a correlation between the operation time, portal hypertension and postoperative intractable ascites. Postoperative histology revealed that a larger number of patients with cirrhosis had intractable ascites (p < 0.05). We conclude that cirrhosis, portal pressure and operating time are the most important factors related to intractable ascites in the case of hepatectomy. Areas of the liver to be resected should be limited in cirrhotic patients with portal hypertension. PMID- 8462922 TI - Utilization of split liver grafts in orthotopic liver transplantation. AB - Among a total of 220 liver transplants, reduced-size liver was used in 21 cases due to discrepancies in size between recipient and donors in 19 patients. In the case of two adult patients suffering from fulminant hepatic failure and in a critical condition, only one donor organ became available, so that the graft was divided to give the two recipients an equal opportunity. The two patients with fulminant hepatic failure were admitted to the ICU requiring mechanical respiration almost at the same time. Hepatitis serologies were HBcAb+, HBsAb+, and VCA+ in one and negative in the second. They had different blood groups (A.Rh+, O.Rh-), and the only donor available was located in Milan, Italy. The graft perfused with UW. was divided into two (right side, segments IV, V, VI, VII, and VIII, and left side, segments I, II and III). The recipients were transplanted 50 and 48 hours after admission. The cold ischemia time was 7.10 and 16.50 hours. The first patient, who received the right lobe, was extubated at 48 hours and discharged on the 40th postransplant day. The second patient remained unconscious with progressive deterioration; an EEG on the 4th day revealed absence of higher cortical function. PMID- 8462923 TI - Clinicopathological characteristics of hepatic hilar bile duct carcinoma. AB - We reviewed thirty cases of hepatic hilar bile duct carcinoma found in 5,800 consecutive autopsy cases, mainly of the aged, and analysed their clinicopathological characteristics. Eleven cases had a record of tumor resection (8 men, 3 women, mean age 75.1 years). At operation, the gross type was mainly infiltrative in all eleven cases, and the stage was II, III or IV in as many as ten cases. Cholecystectomy and bile duct resection were performed in all cases except one in whom additional hepatic lobectomy was performed. In none of the cases was the operation curative. The main cause of non-curability was residual carcinoma on the surgical cut or ablated surface due to longitudinal or lateral cancerous interstitial spread. This was confirmed by the fact that local relapse of carcinoma, either in the hepatic hilus or hepatoduodenal ligament, was found in all the cases at autopsy. This fact also indicates the difficulty in achieving complete resection of carcinoma in this part. On the other hand, a relatively "benign" aspect of hepatic hilar bile duct carcinoma was suggested as follows: 1. Most of the cases were well-differentiated adenocarcinoma. 2. Although there was no case of curative resection, three out of of nine cases (excluding the cases of death during operation) survived more than two years. 3. Distant metastasis found at autopsy was relatively rare, being seen in four of these eleven cases. In the light of these data an operation, even though palliative, is considered to be justified. PMID- 8462924 TI - Clinical significance of serum HBVDNA detected by the PCR method. AB - Changes in serum HBVDNA and their relationship to the prognosis following interferon (IFN) therapy were examined by the polymerase chain reaction (PCR) in 4 patients with chronic hepatitis B infection undergoing IFN therapy. The disappearance of HBVDNA was confirmed by the PCR methods in 3 out of 4 patients who showed favorable subsequent courses. The remaining patient was positive for HBVDNA despite the disappearance of the HBe antigen. In this patient, the hepatitis recurred, and was accompanied by a persistent hepatic disorder. The PCR assay was also carried out to clarify the involvement of the hepatitis B virus in 12 patients who were positive for the HBe antibody and who showed fluctuating transaminase levels. The PCR method revealed that all 12 patients were positive for HBVDNA. These findings indicate the clinical usefulness of the PCR assay for hepatitis B virus infection. PMID- 8462925 TI - Hepatic functional scintigraphic imaging with 99mtechnetium galactosyl serum albumin. AB - 99mTc-galactosyl serum albumin (GSA), a specific radiolabeled synthetic ligand for asialoglycoprotein receptors on hepatocytes, was used for functional liver imaging in 18 patients. Six patients had chronic hepatitis, and 12 had liver cirrhosis. Serial scintigraphic images were obtained for 60 minutes after intravenous administration of 1 mg of the ligand. High-quality images of the liver was obtained in all the patients. Dispersed accumulation in the liver in association with delayed clearance of the ligand from the heart was noted in cirrhotic patients. The activity of the entire liver (L) and that of the heart (H) were measured. The capacity of the liver in terms of elimination of the ligand was estimated by calculating [L/H+L] 15 and 30 minutes after the administration. [L/H+L] showed significant differences between patients with chronic hepatitis and those with liver cirrhosis, and also showed significant correlations with laboratory values such as indocyanine green clearance, prothrombin time, hepaplastin test, serum albumin level, and the Child-Turcotte classification score. 99mTc-GSA might be a useful radiopharmaceutical for obtaining hepatic functional images. PMID- 8462926 TI - Expression of ras and c-myc oncoproteins and hepatitis B surface antigen in human liver disease. AB - One of the major antecedent factors preceding the development of hepatocellular carcinoma is chronic hepatitis B virus infection. Also, recent molecular studies have shown that activation of c-oncogenes might be responsible for the malignant transformation in some cases of hepatocellular carcinoma. We used immunohistochemical methods to investigate the correlation of ras and c-myc oncogene expression with the presence of HBsAg in human liver disease. Our material consisted of 23 chronic active hepatitis B needle liver biopsies and surgical specimens from 11 cases of cirrhosis, 23 hepatocellular carcinoma and 10 normal adult livers. Direct, three-step and streptavidin-biotin-complex immunoperoxidase techniques using polyclonal (anti-HBsAg) and monoclonal antibodies (anti-ras p21, anti-myc p62), were performed. Normal liver tissues were negative for all antibodies used. In HBsAg+ chronic active hepatitis B cases enhancement of c-myc, and less frequently of ras oncogene expression, was a common observation. Increased myc p62 and ras p21 expression was a finding not restricted to HBsAg+hepatocytes, which occasionally were negative for oncoprotein immunostaining. All HBsAg-chronic active hepatitis B cases were negative for ras p21 and myc p62 specific staining. Cirrhotic livers showed more frequently enhanced c-myc expression. Most of the immunostained cells were negative for HBsAg. HBsAg- cases of hepatocellular carcinoma more often showed ras p21 than myc p62 overexpression. HBsAg+ hepatocellular carcinomas presented only ras p21 positive immunostaining, which was not detected in HBsAg+ hepatocytes. Our recent data supports the view that continued expression of HBsAg in human liver disease is not necessary for the enhancement of ras and c-myc oncogene expression. PMID- 8462927 TI - Eosinophilic gastroenteritis: possible role of sonography in diagnosis and follow up. AB - Eosinophilic gastroenteritis (EGE) is a rare disease of unknown etiology. The clinical and radiological diagnoses have to be confirmed by histological examination of biopsy specimens. The authors now present a case of a 19-year-old man with recurrent epigastric pain and vomiting, whose sonographic features and eosinophilia suggested the diagnosis of EGE, which was subsequently confirmed by histology. Sonographic follow-up permitted an effective evaluation of the evolution of the disease under steroid therapy. PMID- 8462928 TI - Secondary early carcinoma in a reconstructed gastric tube after subtotal esophagectomy for early carcinoma of the esophagus. AB - A 70-year-old man was found to have a moderately differentiated squamous cell carcinoma in the mid-esophagus on X-ray and endoscopy. These examinations revealed no lesion in the stomach at that time. Ten days after termination of preoperative hyperthermo-chemo-radiotherapy (HCR), a subtotal esophagectomy and gastric tube reconstruction via the retrosternal route were performed (pTNM stage I). Seven months later, another early cancer was detected in the reconstructed gastric tube. Via a median sternotomy, a wedge resection of the gastric tube was performed, and histopathological studies revealed a well-differentiated adenocarcinoma, which was limited to the submucosa (pTNM stage I). The patient has since done well with no signs of recurrence for the twenty-two months that have elapsed since the second operation was performed. Since the incidence of double cancer in the esophagus and stomach is high, and cases such as that described here will be detected more and more frequently in the future, not only a thorough investigation of a stomach intended for use in the reconstruction of the esophagus, but also strict postoperative checkups of the gastric tube when the esophagus has been reconstructed using the stomach must be considered of great importance. PMID- 8462929 TI - Swallowing function and gastric emptying in patients undergoing replacement of the esophagus. AB - In order to assess functional changes after esophagectomy, esophageal transit scintigraphy and gastric emptying measurements were performed in a group of 10 patients after esophagus substitution by the tubulized stomach, and in a group of 12 patient with an interposed colon. The swallowing function of the rest of the esophagus was preserved in 15 out of 22 patients. The best results were obtained on using a liquid bolus in an upright position, the worst function was found on using a solid bolus in a supine position. Reflux at the level of the anastomosis with the esophagus was detected in only 7 out of 22 patients. The gastric emptying rate was normal in 4 out of 12 examined patients. Scintigraphic methods proved to be suitable for the detection of functional changes after surgery. The function tests performed proved that substitution of the esophagus by either tubulized stomach or interposed colon provides the patient with adequate comfort, provided that he adopts certain habits. PMID- 8462930 TI - Pancreatic duct width: its significance as a diagnostic criterion for pancreatic disease. AB - The significance of main pancreatic duct width in the diagnosis of pancreatic disease, was studied in 338 endoscopic retrograde pancreatographies. Two hundred and forty patients referred for suspected biliary disease had normal pancreatograms (Group 1), 60 had pancreatic carcinoma (Group 2) and 38 had a history and pancreatogram compatible with chronic pancreatitis (Group 3). After categorizing patients by decade, in group 1 the effect of aging on the pancreatic duct width in the head, body and tail (F5,234 > 3.71, p < 0.003) was pronounced, especially after the fifth decade. There was a significant difference between groups 1, 2 and 3 in terms of the width of the main pancreatic duct in all three parts of the pancreas (F2,325 > 42.24, p < 0.001). The upper range of normal pancreatic duct width was 8.0 mm, 4.0 mm and 2.4 mm in the head, body and tail, respectively. Abnormal ductograms were wider than the normal ranges in the head, body and tail of the pancreas in 14%, 49% and 59% (p < 0.001) of the patients, respectively. Establishing normal ranges of the pancreatic duct width may help in the diagnosis of pancreatic disease. Measurements in the body and tail, as compared with the head, are a more sensitive indicator of pancreatic duct dilation. PMID- 8462931 TI - Association between gallbladder cancer and anomalous union of the pancreaticobiliary ductal system. AB - Between 1978 and 1989, gallbladder cancer was diagnosed in 17 out of 48 patients with anomalous union of the pancreaticobiliary system. The clinical, surgical, and pathological features of these 17 patients are described. We classified them into two groups, those with and those without dilation of the common bile duct, and compared the clinicopathological features. Patients with dilation of the bile duct often had early onset of symptoms, so that cancer was detected at a relatively early stage. Most of those without dilation of the common bile duct already had a number of severe symptoms at the first consultation, and the cancer was usually at an advanced stage. We believe that early diagnosis of patients without dilation of the bile duct is an important clinical problem that needs to be resolved. PMID- 8462932 TI - Albumin inhibits hemolysis of erythrocytes induced by ethanolamine oleate during endoscopic injection sclerotherapy. AB - In attempts to avoid hemolytic nephropathy following injection of 5% ethanolamine oleate during endoscopic injection sclerotherapy for esophageal varices, the relationship between serum levels of albumin and hemolysis induced by ethanolamine oleate was investigated. The rate of hemolysis at various concentrations of ethanolamine oleate and albumin was examined using a spectrophotometer in ten cirrhotic patients and five healthy volunteers (controls). Hemolysis induced by ethanol-amine oleate increased in an ethanolamine oleate concentration-dependent fashion (p < 0.01) but was dose dependently inhibited by albumin (p < 0.05). The state of liver function was unrelated to the rate of hemolysis. The relationship between hemoglobinuria and serum albumin levels in seventy-nine cirrhotic patients with esophageal varices treated by endoscopic injection sclerotherapy with ethanolamine oleate was also examined. Hemoglobinuria was evident in 20 out of 24 patients (83.8%) in whom the serum albumin level was less than 3.0 g/dl, and in 24 out of 55 (43.6%) in whom it exceeded 3.0 g/dl, the difference being statistically significant (p < 0.01). On the day after endoscopic injection sclerotherapy, creatinine clearance fell from 81.6 +/- 33.8 m/l min to 60.1 +/- 31.4 ml/min in the hemoglobinuria-positive patients (p > 0.01) and two went into acute renal failure. The creatinine clearance ranged from 79.5 +/- 27.9 ml/min to 83.0 +/- 39.9 ml/min in the hemoglobinuria-negative patients (p < 0.1). In the light of this evidence we correct the serum albumin level cut off point to 3.0 g/dl prior to endoscopic injection sclerotherapy in order to maintain renal function. PMID- 8462933 TI - Definition and diagnosis of early cancer of the biliary tract. AB - From the study on correlation between the depth of cancer invasion and the results of surgery, early cancer of the biliary tract may be defined as cancer cell invasion limited to the mucosal or muscularis propria in the case of carcinoma of the gallbladder, and to the mucosal or fibro-muscular layer in the case of carcinoma of the bile duct. With few exceptions, these tumors had no lymph node metastasis, venous invasion, perineural infiltration or involvement of the lymphatic vessels. Since the cumulative 5-year survival rate was 100% after resection of early cancer, the choice of surgical procedures was considered to be extended cholecystectomy for early cancer of the gallbladder, and the standard radical resective operation for early cancer of the bile duct. An accurate diagnosis was not made preoperatively in most cases of early cancer of the biliary tract. The diagnostic approach is discussed, including the recently developed imaging modalities, such as endoscopic ultrasonography and percutaneous transhepatic cholecystoscopy or cholangioscopy. PMID- 8462934 TI - Acute abdomen caused by torsion of the pedicle in a wandering spleen. AB - A case of acute abdomen caused by acute torsion of a wandering spleen in a 20 year-old female patient is presented. It underscores the efficiency of the ultrasonic examination in the diagnosis of this type of pathology. PMID- 8462935 TI - Ending stigma and discrimination begins at home. PMID- 8462936 TI - Confidentiality in group therapy. PMID- 8462937 TI - Ten trends in managed care and their impact on the biopsychosocial model. PMID- 8462938 TI - The agitated patient, Part I: Evaluation and behavioral management. PMID- 8462939 TI - When a therapist overindulges a demanding borderline patient. PMID- 8462940 TI - The video violence debate. AB - Some researchers and theorists are convinced that graphic scenes of violence on television and in movies are inextricably linked to human aggression. Others insist that a link has not been conclusively established. This paper summarizes scientific studies that have informed these two perspectives. Although many instances of children and adults imitating video violence have been documented, no court has imposed liability for harm allegedly resulting from a video program, an indication that considerable doubt still exists about the role of video violence in stimulating human aggression. The author suggests that a small group of vulnerable viewers are probably more impressionable and therefore more likely to suffer deleterious effects from violent programming. He proposes that research on video violence be narrowed to identifying and describing the vulnerable viewer. PMID- 8462941 TI - Residents' and nurses' perceptions of difficult-to-treat short-stay patients. AB - OBJECTIVE: Characteristics attributed by nurses and by psychiatric residents to difficult-to-treat inpatients in a short-stay setting were compared to determine whether discipline-specific perceptions of such patients existed. METHODS: A total of 117 patients consecutively admitted to a short-stay inpatient unit were assessed by both psychiatric residents and nurses during the third week of hospitalization using subscales of the Hospital Treatment Rating Scales. The degree of management difficulty presented by each patient in 28 areas was rated, and an overall rating was calculated. Two separate regression analyses were used to examine characteristics of patients rated difficult. RESULTS: Self-harm behaviors, violence toward others, and behaviors that sabotage treatment were identified by both nurses and residents as characteristics of difficult patients, although these characteristics contributed less to residents' perceptions of patient difficulty than to nurses'. For nurses, the most important additional characteristics contributing to treatment difficulty were related to patients' inability to form a therapeutic alliance. For residents, by far the most significant contributor to overall treatment difficulty was lack of response to medication. CONCLUSIONS: The discipline-specific differences in perceptions of difficult-to-treat patients were associated with differences in professional roles. Communication problems between physicians and nurses may be due in part to their different perceptions of treatment and management difficulty. PMID- 8462942 TI - Patients' fear of and objection to electroconvulsive therapy. AB - Patients' fear of and objection to electroconvulsive therapy (ECT) have complicated the administration of this modality since its inception. Despite modifications in technique and pretreatment education over the years, these problems have not disappeared. The author discusses the literature on fear of convulsive therapy and provides three case examples from his clinical experience. The review suggests that some patients gradually develop a pathological fear of ECT over the course of treatment, which creates a significant obstacle to compliance and in some cases leads to refusal of treatment. The author suggests that this clinical phenomenon, described during the 1950s but often underrecognized today, merits further study. PMID- 8462943 TI - Assessing psychiatric patients' competency to agree to treatment plans. AB - The issue of therapists' liability for patients who commit suicide may depend on whether courts view the suicidal patient as competent to decide to follow or not follow an agreed-upon treatment plan. Therapists have not been found liable for malpractice when courts have viewed a patient's decision not to seek help when feeling suicidal as being voluntary rather than reflecting global incompetence due to mental illness. The author offers practical suggestions, including sets of specific questions, for assessing and documenting a psychiatric patient's competency to agree to a treatment plan. An important element of the procedure is direct assessment of the patient's understanding of the risks of withholding information from caretakers and the benefits of providing it. Such competency assessments can facilitate clinical management of patients and can also help reduce the risk of malpractice liability resulting from patients' suicide. PMID- 8462944 TI - Long-term psychotherapy and informed consent. AB - Many long-term psychotherapies begin without sufficient attention to an informed consent process. Failure to obtain informed consent may leave patients ill prepared to question the recommendation for long-term psychotherapy or to make alternate treatment choices. The author presents a model for informed consent to stimulate debate on ethical approaches to this type of treatment. The approach covers six areas therapists should discuss with candidates for long-term psychotherapy: the diagnostic model used and the recommendation for treatment, potential risks and benefits of treatment, availability of less expensive short term interventions, clarification of the necessity for psychotherapy, limits of insurance coverage, and plans for measuring the patient's response to treatment. The decision to recommend long-term psychotherapy should be made through careful analysis of indications and contraindications for such treatment and in the context of informed consent. PMID- 8462945 TI - Hospital characteristics, diagnoses, and staff reasons associated with use of seclusion and restraint. AB - OBJECTIVE: Patterns of seclusion and restraint over a one-year period at 82 Veterans Affairs medical centers were examined to determine whether use of these interventions was influenced by hospital characteristics (such as geographic location, per diem cost, patient-staff ratio, and university affiliation), patient diagnoses, or reasons for use. METHODS: For comparison, medical centers were grouped into seven geographic regions and into three frequency-of-use groups. Mean use rates and hospital characteristics were examined by rank correlational analysis. RESULTS: Among hospital characteristics, only geographic location was associated with differences in use of seclusion and restraint. Mean rates of use in the Pacific and Mid-Atlantic regions were significantly lower than those in other regions. Total hours of seclusion and restraint at the 20 highest-use centers differed from those at the 20 lowest-use centers by a factor of ten. Patients with schizophrenic disorders were secluded or restrained most frequently. Centers with the highest rates used these interventions most frequently for reasons not associated with violent or potentially violent behaviors. CONCLUSIONS: The large geographic variations in use of seclusion and restraint may be a function of different standards of practice or of different state laws. PMID- 8462946 TI - Frequent psychiatric visitors to a Veterans Affairs medical center emergency care unit. AB - OBJECTIVE: The study examined characteristics of patients who made repeat visits to the psychiatric emergency service of a Veterans Affairs medical center. METHODS: Computer records of patients who visited the emergency service were retrospectively examined for a one-year period after their index visit. Patients were divided into three groups according to the number of visits; nonrepeaters had only one visit, occasional repeaters had two or three visits, and frequent repeaters had four or more visits. RESULTS: Of 1,144 patients who visited the emergency service during the one-year study period, 26 percent were occasional repeaters and 8 percent were frequent repeaters; the latter group accounted for 24 percent of all visits. Schizophrenic patients were overrepresented among frequent repeaters. Compared with nonrepeaters, repeat visitors were admitted to the hospital more often and were less likely to be referred to an outpatient clinic for follow-up. Frequent repeaters were more likely than occasional repeaters to revisit within one month and to visit during evening hours. CONCLUSIONS: One-third of patients seen during a one-year period revisited the emergency service, a rate substantially higher than those reported for large urban non-VA hospitals. The higher rate may have been due to the longer sampling period, to a more seriously ill population, or to fewer community resources for veterans because of misperceptions about their eligibility. PMID- 8462947 TI - Characteristics of repeat users of a psychiatric emergency service. AB - OBJECTIVE: Patients who visited a psychiatric emergency service were studied to determine whether repeat visitors, who consume a disproportionate share of services, could be identified by demographic and diagnostic characteristics. METHODS: Data were obtained from a semistructured diagnostic interview given to all 16,257 persons who made 29,214 visits to an urban psychiatric emergency service in Pittsburgh, Pennsylvania, from 1985 to 1989. Patients were categorized into four groups based on the number of visits in the five-year period. Patients in group 1 made a single visit, while those in group 2 averaged less than one visit per year; those in group 3 made one or two visits per year, and those in group 4, more than two visits per year. RESULTS: Groups 3 and 4 constituted 5.1 percent of the sample but made 27.1 percent of the total visits. Repeat users were significantly more likely to be male, younger, unmarried, unemployed, and nonwhite and to have diagnoses of schizophrenia, other psychotic disorders, and personality disorders. CONCLUSIONS: Repeat users of psychiatric emergency services appear to have demographic and diagnostic characteristics that may permit their early identification. For such patients, implementation of alternative management strategies, such as intensive case management, may reduce their use of services. PMID- 8462948 TI - Prevalence of psychopathology in elderly persons in nursing homes and in the community. PMID- 8462949 TI - Using interactive video to supplement HIV counseling. PMID- 8462950 TI - Violence toward family caregivers by mentally ill relatives. PMID- 8462951 TI - Ethics and the expert witness. PMID- 8462952 TI - Hospital advertising. PMID- 8462953 TI - Outdated information. PMID- 8462954 TI - Collaboration. PMID- 8462955 TI - Staff in state hospitals. PMID- 8462956 TI - Concern for public hospitals. PMID- 8462957 TI - No nurse cap needed. PMID- 8462958 TI - No volunteer coverage. PMID- 8462959 TI - Shared sacrifice: the right message for America. AB - Is President Clinton naive to ask Americans to buy into "shared sacrifice"? Actually, shared sacrifice seems the right message for America in the 1990s, writes Dick Davidson, president of the AHA. In fact, he says, it's probably the only way we'll be able to repair our economy and our health care system. PMID- 8462960 TI - Health care reform: nursing's vision of change. AB - "Health care reform will change the role of nursing more dramatically than that of any other health care profession," says one nursing educator. Her statement is echoed by leaders of a variety of groups. The issue, everyone agrees, is how that role will change. And leaders of organized nursing and organized medicine find themselves scattered across a spectrum of opinion on that critical question. PMID- 8462961 TI - The data debate. CIOs weigh issues, obstacles to information networks. Panel discussion. AB - CEOs are looking toward the development of provider networks in a post-reform environment, as envisioned in the AHA's proposal for Community Care Networks. But CIOs face conceptual and technical challenges on the path to true information networking. An exclusive Hospitals panel discussion. PMID- 8462962 TI - Future fears: organized medicine faces managed competition. PMID- 8462963 TI - Funding risks. Rising health care costs and the current public policy climate. PMID- 8462964 TI - Benefits equity. Providers anticipate core mental health coverage. AB - In recent years, payer restrictions have led to many belt-tightening measures in the psychiatric field. But word that the administration may expand mental health insurance coverage has provided a needed shot in the arm for that field. PMID- 8462966 TI - Do physicians and hospitals share capitation? PMID- 8462965 TI - Medicare meets reform. Integrating Medicare poses a puzzle for reformers. AB - Many reformers say reform must extend to Medicare to control rising costs. But getting Medicare patients to embrace managed care, and melding disparate payment methods during the transition, will pose major challenges. PMID- 8462967 TI - Medical waste transport issues aired. PMID- 8462968 TI - OIG stance causes concern over purchases. PMID- 8462969 TI - Data watch. Fourth-quarter data from AHA Monitrend II. PMID- 8462970 TI - Proving our value: why we documented it. PMID- 8462971 TI - Molecular cytogenetic study of patients with Pallister-Killian syndrome. AB - The Pallister-Killian syndrome (PKS) is characterized by tissue limited chromosomal mosaicism, i.e. the presence of a supernumerary metacentric chromosome [i(12p)] often confined to skin fibroblasts while the karyotype of cultured lymphocytes is normal. In the present study, chromosome painting by chromosomal in situ suppression (CISS) hybridization and interphase cytogenetic procedures employing biotinylated or digoxigenin labelled probes was carried out. These probes comprised a chromosome 12 specific library (LA 12NS01) and chromosome 12 centromere specific alpha-satellite (pSP12-1). They were used to analyse and quantify the presence of i(12p) in lymphocytes, granulocytes/monocytes, skin fibroblasts and buccal mucosal cells from five patients and one aborted fetus with PKS, and ten normal donors. CISS hybridization on mitotic skin fibroblasts reliably indicated the presence of i(12p) cells, even when metaphases of poor quality were included in the analysis. Two of the five patients showed i(12p) in a small proportion (< or = 0.5%) of the cultured lymphocytes too. The interphase cytogenetics procedure did not reveal the isochromosome in lymphocytes or granulocytes/monocytes in any of the patients. Two of the six patients had a twofold increase in the number of buccal mucosal cells with three hybridization signals over control values. However, for mucosal cells, methodological improvements are required. For cytogenetic diagnosis of PKS, cultured fibroblasts subjected to chromosome painting by CISS hybridization with a chromosome 12 specific library probe are recommended. PMID- 8462972 TI - Efficient identification of marker chromosomes in 27 patients by stepwise hybridization with alpha-satellite DNA probes. AB - Using a procedure involving stepwise hybridization of alpha-satellite DNA probes at various conditions of stringency, 33 marker chromosomes from 27 patients were identified. The markers were ascertained prenatally in fetal amniotic fluid and chorionic villi samples or postnatally in blood from liveborn children. The marker chromosomes first were characterized by cytogenetic techniques and later identified by fluorescence in situ hybridization. There were 14 bisatellited markers, 3 metacentric nonsatellited marker chromosomes, 2 nonsupernumerary sex chromosomal rings, and 9 patients carrying markers that appeared to be small rings. Multiple stringency conditions were used for the identification of 14 supernumerary ringlike chromosomes detected in 8 patients. Ring-like markers were initially screened at low stringency and grouped into alpha-satellite families. Subsequent higher stringency hybridization led to marker identification. Ringlike chromosomes originated from chromosomes 1, 2, 8, 12, 13 or 21, 14 or 22, 15, 18, and X. Multiple ringlike markers ascertained in a single patient were determined to originate from different chromosomes. PMID- 8462973 TI - A missense mutation in the low density lipoprotein receptor gene causes familial hypercholesterolemia in Sephardic Jews. AB - Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low density lipoprotein (LDL) receptor gene. Here, we characterize an LDL receptor mutation that is associated with a distinct haplotype and that causes FH in the Jewish Sephardic population originating from Safed, a town in northern Israel. The mutation was found in eight FH families originating from this community comprising 10% of heterozygote FH index cases screened in Israel. The mutation was not found in four additional FH heterozygotes whose hypercholesterolemia co-segregated with an identical LDL receptor gene haplotype. A guanine to cytosine substitution results in a missense mutation (asp147 to his) in the fourth repeat of the binding domain encoded by exon 4 of the LDL receptor gene. The mutant receptor protein was synthesized in cultured cells as a 120 kDa precursor form that failed to undergo normal processing to a mature cell surface form. Most of the receptor precursors were degraded in the endoplasmic reticulum. The small number of mutant receptors on the cell surface were unable to bind LDL or beta very low density lipoprotein. The abnormal behavior of the mutant receptor was reproduced by site-directed mutagenesis and expression of the mutant protein in CHO cells. The mutation can be diagnosed by allele-specific oligonucleotide hybridization of polymerase chain reaction amplified DNA from FH patients. PMID- 8462974 TI - A new human brain cDNA molecule: assignment to chromosome 11q21-q23.1 and description of two polymorphisms studied by the polymerase chain reaction. AB - A new human brain cDNA molecule was mapped by in situ hybridization to the 11q21 q23.1 region of the human genome, probably to the 11q22 band. An EcoRI restriction site and a (GT)n repeat element within the gene were shown to be polymorphic. Both polymorphisms were readily studied by the polymerase chain reaction. A two-allele polymorphism was described for the EcoRI restriction site, whereas four different alleles were detected for the second genetic marker. The observed heterozygosities were 37% and 42% for the former and the latter polymorphism, respectively. The combined heterozygosity index was estimated to be 0.56. These new genetic markers will be useful for linkage analysis of neurogenetic diseases that have been mapped to this chromosomal region. PMID- 8462975 TI - Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydrogenase-B(H) deficiency using DNA conformation polymorphism analysis and silver staining. AB - Human lactate dehydrogenase (LDH)--B(H) mutant genes were analyzed by polymerase chain reaction (PCR) and DNA conformation polymorphism. We used polyacrylamide gradient gel and silver staining procedures for DCP analysis, and observed abnormal migration patterns in individuals heterozygous for the LDH-B deficiency. Subsequent sequence determination of the mutant alleles consistently resulted in detection of three single base substitutions (transversions), viz., a C to A at residue "35" (GCG, Ala-->GAG, Glu), a T to G at residue "172" (TTT, Phe-->GTT, Val), and an A to T at residue "176" (ATG, Met-->TTG, Leu). Furthermore, mismatched PCR or amplification refractory mutation system was developed for the rapid screening and confirmation of these mutations. These amino acid replacements may cause conformational changes in neighboring residues; this probably affects the active site arrangement and results in the loss of enzyme activity. PMID- 8462976 TI - Are the nail-patella syndrome and the autosomal Goltz-like syndrome the phenotypic expressions of different alleles at the COL5A1 locus? AB - The COL5A1 gene, which encodes the pro alpha 1(V) chain, was recently mapped to 9q34.3 in the same region as the nail-patella locus. This was taken as an indication that the nail-patella syndrome may be an inherited connective tissue disorder. We demonstrate COL5A1 heterozygous deletion and fibroblast under expression of alpha 1(V) chains in a girl with an unbalanced translocation resulting in 9q32-->qter monosomy. The patient presents dysplastic nails, a sign typical of nail-patella syndrome, but normal patella. Moreover, she has skin and bone disorders similar to those found in the Goltz syndrome. We suggest that monosomy for the COL5A1 gene is responsible for these connective tissue disorders. Accordingly, the nail-patella syndrome could be attributable to mutations inside the COL5A1 gene rather than to a deletion of it. PMID- 8462977 TI - Physical mapping identifies DXS265 as a useful genetic marker for carrier detection and prenatal diagnosis of X-linked agammaglobulinemia. AB - The gene responsible for X-linked agammaglobulinemia (XLA) has not been identified; however, in the course of genetic linkage studies designed to map the locus more precisely, a number of closely linked polymorphic loci have been identified. These have proved to be useful in identifying carriers and in pre natal diagnosis of this disease. The DXS178 locus was found to be closest to the XLA locus and has been the most usefully employed probe to date. Using physical mapping techniques, we have identified a previously cloned genetic marker, DXS265, as being situated within 5 kb of DXS178. So far, we have found one family that is not informative for DXS178 but that is informative for DXS265; females in this family can now be offered the possibility of carrier determination and pre natal diagnosis for this life-threatening disease. PMID- 8462978 TI - Deletion breakpoints associated with the Prader-Willi and Angelman syndromes (15q11-q13) are not sites of high homologous recombination. AB - Deletions of 15q11.2-q12 are associated with either the Prader-Willi (PWS) or Angelman (AS) syndromes. It has been suggested that excessive recombination in this region might explain the high frequency of such deletions, and the frequent involvement of chromosome 15 in translocations and nondisjunction. We have studied recombination in the PWS region by linkage analysis of non-PWS families. No recombination was found (with maximum lod scores greater than 3.0) for most pair-wise combinations of probes: 39, IR4-3R, ML34, 189-1, 3-21. A 'hotspot' of recombination is observed between loci detected by p3-21 and pIR10-1. The female recombination fraction in this region was significantly higher than that for males. Close linkage with 0.06 recombination was found for the IR10-1 and CMW-1 pair. No excess recombination was found between sites bounding common breakpoints observed in deletions associated with PWS and AS. It is suggested that these deletions form frequently because of the presence of duplicated DNA sequences and/or inversions in this region, and not because of a high rate of homologous recombination. PMID- 8462979 TI - Changes of telomere lengths in human intracranial tumours. AB - The termini of human chromosomes comprise stretches of G-rich repeats that are about 5-20 kilobase (kb) in length. The size of the telomeres can be determined by hybridization with probes specific for these (ttaggg)n sequences after digestion of chromosomal DNA with appropriate restriction enzymes and electrophoretic separation of the fragments. Here, probing with the 32P-labelled synthetic (TTAGGG)3 oligonucleotide revealed length changes of the telomeres occurring in intracranial tumours. Among 60 samples, analysed, 41.7% showed telomere elongation, and 21.7% telomere reduction, whereas 36.7% of the tumours exhibited equal lengths compared with the patients' peripheral blood leukocytes. Most of the elongated glioma telomeres exceeded in length those of untransformed astrocytes derived from human fetal tissue. PMID- 8462980 TI - A novel nonsense mutation in the protein C (PROC) gene (Trp-29-->term) causing recurrent venous thrombosis. AB - A novel heterozygous TGG-->TAG (Trp-29-->Term) substitution was detected in three members of a family with inherited type 1 protein C deficiency and recurrent venous thrombosis. PMID- 8462982 TI - Combining mass media and contest in smoking cessation. An experience from a series of national activities in Finland. PMID- 8462983 TI - Indian culture--symbols as communication tools. PMID- 8462984 TI - New challenges for health promotion through mass-media. PMID- 8462985 TI - South East Asia: intercountry consultative meeting on comprehensive school health education. A call for action to implement and strengthen comprehensive approaches to school health education in South East Asia. PMID- 8462986 TI - Health education through mass media. PMID- 8462981 TI - Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants. AB - Various processes (selection, mutation, migration and genetic drift) are known to determine the frequency of genetic disease in human populations, but so far it has proved almost impossible to decide to what extent each is responsible for the presence of a particular genetic disease. The techniques of gene and haplotype analysis offer new hope in addressing this issue, and we review relevant studies of three haemoglobinopathies: sickle cell anaemia, and alpha and beta thalassaemia. We show how for each disease it is possible to recognize a pattern of regionally specific mutations, found in association with one or a few haplotypes, that is best explained as the result of selection; other patterns are due to population migration and genetic drift. However, we caution that such conclusions can be drawn in special circumstances only. In the case of the haemoglobinopathies it is possible because a selective agent (malaria) was already suspected, and the investigations could be carried out in relatively genetically homogenous populations whose migratory histories are known. Moreover, some data reviewed here suggest that gene conversion and the haplotype composition of a population may affect the frequency of a mutation, making interpretation of gene frequencies difficult on the basis of standard population genetics theory. Hence attempts to use the same approaches with other genetic diseases are likely to be frustrated by a lack of suitably untrammelled populations and by difficulties accounting for poorly understood genetic processes. We conclude that although this combination of molecular and population genetics is successful when applied to the study of haemoglobinopathies, it may not be so easy to apply it to the study of other genetic diseases. PMID- 8462987 TI - Africa: using radio soap operas to promote family planning. AB - Programmes that combine mass media and popular entertainment formats can be a potent force in health communication since they can reach large audiences with persuasive messages. Not only can such programmes increase knowledge and stimulate approval, but also, when used effectively, they can change behaviour. PMID- 8462988 TI - Cloning of the beta 2-microglobulin gene in the zebrafish. AB - The beta 2-microglobulin (beta 2m) is a protein found in the serum in a free form and on the cell surface in a form noncovalently associated with the alpha chain of the class I major histocompatibility complex (Mhc) molecules. In mammals, the beta 2m-encoding gene (B2m) is found on a chromosome different from the Mhc proper. We have isolated and characterized the B2m gene of the zebrafish, Brachydanio rerio, family Cyprinidae. We obtained both cDNA and genomic clones of the Brre-B2m gene. The cDNA clones contained the entire coding sequence, the entire 3' untranslated (UT) region, and at least part of the 5'UT region. The genomic clone contained the entire Brre-B2m gene. The coding sequence specifies 97 amino acid residues of the mature protein so that the zebrafish beta 2m is two residues shorter than human and one residue shorter than cattle, fowl, or turkey beta 2m (codons at positions 85 and 86 have been deleted in the Brre-B2m gene). The amino acid and nucleotide sequence similarities between zebrafish and human beta 2m (B2m) are 45% and 59%, respectively. Approximately 24% of the positions are invariant and an additional 9% show only conservative substitutions in comparisons which include all known beta 2m sequences (fish, avian, and mammalian). Most of the conserved positions are in the beta strands (some 47% of the beta-strand positions are conserved in the three vertebrate classes). The Brre-B2m gene consists of four exons separated by three introns. All of the introns are considerably shorter than the corresponding introns in the mammalian B2m genes. The coding sequences of the cDNA and the genomic clones are almost identical but the sequences of the 3'UT regions differ at 1.7% of the sites, suggesting that the genes borne by these clones might have diverged at least 0.7 million years (my) ago. In contrast to the human B2m gene, the Brre-B2m gene shows no bias in the distribution of the CpG dinucleotides: the dinucleotides are distributed evenly along the entire available sequence. The haploid genome of the zebrafish contains only one copy of the B2m gene. PMID- 8462989 TI - Sequence and evolution of cattle MHC class I cDNAs: concerted evolution has not taken place in cattle. AB - To explore genetic mechanisms responsible for major histocompatibility complex (MHC) class I evolution in the artiodactyls, we cloned and sequenced MHC class I cDNAs from a Bos taurus bull heterozygous for cattle MHC (BoLA) class I serological specificities w2 and w30. Four unique cDNAs were found, indicating the presence of at least two MHC class I loci. Analysis of these four cDNAs and all previously published BoLA cDNA sequences suggested that there may be three cattle MHC class I loci. Additionally, comparison of all of the BoLA class I cDNAs to MHC class I cDNAs of other artiodactyls showed that some of the BoLA class I cDNAs were more similar to certain sheep cDNAs than they were to other cattle cDNAs. These data indicate that each BoLA class I locus has evolved independently after an ancestral gene duplication event and that inter-locus segmental exchange or concerted evolution has not occurred rapidly enough to cause extensive divergence between the orthologous MHC class I loci of sheep and cattle. PMID- 8462990 TI - Polymorphism in the regulatory region of HLA-DRB genes correlating with haplotype evolution. AB - Class II genes of the human major histocompatibility complex (MHC) are polymorphic. Allelic variation of the coding region of these genes is involved in the antigen presentation and is associated with susceptibility to certain autoimmune diseases. The DR region is unique among human class II regions in that multiple DRB genes are expressed. Differential expression of the different DRB loci has been demonstrated, and we sequenced the proximal promoter region of the HLA-DRB genes, known to be involved in the regulation of these genes. We found locus-specific and allele-specific nucleotide variations in their regulatory regions and we determined the relationship between the regulatory regions of HLA DRB genes. This polymorphism found in the regulatory conserved boxes could be involved in the observed differential expression of DRB loci. In addition, we found a polymorphism between the regulatory regions of DRB1 alleles which might be involved in an allele-specific regulation and therefore could be considered as an additional factor in susceptibility to autoimmune diseases. PMID- 8462991 TI - Characterization of beta 2-microglobulin transcripts from two teleost species. AB - Using degenerate primers based on published beta 2-microglobulin sequences we were able to obtain an expected 111 base pairs (bp) polymerase chain reaction (PCR) fragment from tilapia genomic DNA. The sequence of this fragment showed a high degree of similarity to mouse beta 2-microglobulin at the protein level. We used these primers in an "anchored PCR" to obtain a 213 bp PCR fragment from a carp cDNA library. This was then used to clone a full-length beta 2-microglobulin cDNA from carp. The carp sequence showed the highest similarity to rabbit beta 2 microglobulin. Both sequences showed strong similarities to all previously published vertebrate beta 2-microglobulin sequences. The predicted protein secondary structure of both the carp and tilapia clones was almost identical to the corresponding regions of previously known vertebrate beta 2-microglobulin protein sequences. When either the carp or tilapia probes were used against corresponding northern blots, they hybridized to a message of approximately 800 1000 bases long, which corresponds to the previously published lengths of beta 2 microglobulin mRNAs. Southern blotting indicated that beta 2-microglobulin was encoded by a single copy gene in both cases. Phylogenetic analysis indicated that the sequences were related to the beta 2-microglobulins of higher vertebrates but grouped together in an ancestral position. PMID- 8462992 TI - Preimplantation mouse embryos express Mhc class I genes before the first cleavage division. AB - We have used oligonucleotide primers complementary for polymorphic regions of the mouse H-2D gene in a highly sensitive polymerase chain reaction (PCR) assay to detect the transcription of maternal and paternal class I mRNAs in gametes and preimplantation embryos. Using congenic strains of mice differing only at the major histocompatibility loci, class I (H-2D) mRNA of both the maternal and paternal haplotypes was demonstrated in embryos from the one-cell zygote to the late blastocyst stage of development but could not be detected in vas deferens or in vitro capacitated sperm or in ovulated secondary oocytes. These data clearly show that both paternally and maternally inherited Major histocompatibility complex (Mhc) class I genes are transcribed from the earliest stages of embryonic development, and suggest that developmental regulation of expression of their protein products is principally at the post-transcriptional level. PMID- 8462993 TI - HLA class I binding of synthetic nonamer peptides carrying major anchor residue motifs of HLA-B27 (B*2705)-binding peptides. AB - Eight nonamer peptides that comply with the major anchor residue motifs (the combination of amino acid residues at positions 2 and 9), R - K and R - R, of HLA B27 (B*2705)-binding peptides were synthesized and tested for their direct binding to HLA class I alpha chains by the HLA class I alpha chain refolding assay previously described. One was a known B27 (B*2705)-binding heat shock protein peptide, HSP89 alpha (201-209), and the other seven were derived from the sequence of wild-type P53, a human tumor suppressor protein. A total of 36 HLA class I allospecificities were tested. HSP89 alpha (201-209) and two P53 peptides, P53 (362-370) and P53 (378-386), all possessing the motif R - K, bound strongly to B27 (B*2705) alpha chains. A weak binding was seen for P53 (272-280) and P53 (334-342), both showing the motif R - R. Most of these B27-binding peptides were found to bind to A3 alpha chains as well. In addition, P53 (173 181) and P53 (334-342), both with the R - R motif, showed substantial binding with A31 alpha chains. All the peptides carrying the motif R - K also showed weak binding with A31 alpha chains. The remaining two peptides, P53 (201-209) and P53 (282-290), with the motif R - R, did not show significant binding with any of the alpha chains tested. This study demonstrates both the specificity of peptide binding to a given HLA allelic product and the occurrence of cross-peptide binding between the allelic products of different HLA loci. PMID- 8462995 TI - Evidence of positive selection at the Lyb-2 locus of the mouse. PMID- 8462994 TI - A novel coding sequence belonging to a new multicopy gene family mapping within the human MHC class I region. AB - The human major histocompatibility complex (MHC) region is a genomic region spanning about 4000 kilobases (kb) including the class I, class II, and class III subregions. The class I subregion is larger than the two others but with fewer genes described to date. It includes a) classical human leucocyte antigen (HLA) class I genes (HLA-A, HLA-B, HLA-C) which are highly polymorphic and encode products presenting the endogenous antigenic peptides to the T-cell receptors, and b) non-classical class I genes (HLA-E, HLA-F, HLA-G) whose function is still unknown. In this study, we describe the first coding sequence which is not structurally related to the class I genes, although it is localized within the MHC class I region. This novel gene, P5-1, belongs to a multiple copy family, all members of which map within the MHC. Although the P5-1 sequence showed no similarity to sequences in different databanks, its transcription, which is restricted to lymphoid tissues, argues for an immunological function of its product. PMID- 8462996 TI - Assignment of three human high-affinity Fc gamma receptor I genes to chromosome 1, band q21.1. PMID- 8462997 TI - Isolation and sequence analysis of cDNA for the dog T-cell receptor Tcr alpha and Tcr beta chains. PMID- 8462998 TI - Human T-cell receptor TCRAV, TCRBV, and TCRAJ sequences newly found in T-cell clones reactive with allogeneic HLA class II antigens. PMID- 8462999 TI - Diversity of exon 2 of major histocompatibility complex class I genes in wild mice. PMID- 8463000 TI - DR2 haplotypes (DRB1, DQA1, DQB1) associated with systemic lupus erythematosus. PMID- 8463001 TI - A new HLA-DPB1 allele from Santa Cruz Island, Solomon Islands. PMID- 8463002 TI - A second new HLA-DPB1 allele from Santa Cruz Island, Solomon Islands. PMID- 8463003 TI - The production of coronary vasoconstrictor substances by freshly harvested endothelial cells. AB - The effects of cell free superfusates from freshly harvested bovine endothelial cells attached to microcarrier beads on the isolated rabbit and rat heart and on superfused rabbit jugular veins were observed. Cell free conditioned filtrates from freshly harvested cells caused marked diminution in coronary flow and cardiac output in the isolated rabbit heart; in the perfused rat heart an increase in coronary perfusion pressure and a decline in left ventricular systolic tension and maximal left ventricular contractility (dP/dt) were recorded. Marked differences were found between changes induced by conditioned filtrate as compared to synthetic endothelin. Endothelin as present in conditioned filtrate could not account for the pronounced effect on coronary perfusion pressure, dp/dt and cardiac output induced by conditioned filtrate; more than one hundred times that of synthetic endothelin was needed to achieve comparable cardiodynamic effects. This suggested that additional non-prostanoid vasoconstrictor substance or substances are produced by freshly harvested endothelial cells. This conclusion was supported by the observation that BQ-123, a specific inhibitor of endothelin A (ETA) receptor significantly prevented contractions by endothelin, while failing to inhibit those induced by freshly harvested endothelial cells. These constrictor substances may be leukotrienes. PMID- 8463004 TI - Prostacyclin analogue, beraprost, sustains recanalization duration after thrombolytic therapy in acute myocardial infarction model. AB - Platelets play an important role in acute reocclusion after thrombolysis in acute myocardial infarction. We tested a new antiplatelet agent, the stable prostacyclin analogue, beraprost, in the prevention of reocclusion of reperfused vessels with a combination of recombinant tissue-type plasminogen activator (rt PA) in a canine preparation of coronary artery thrombosis superimposed on high grade stenosis. Intravenous infusion of rt-PA (17 micrograms/kg/min for 30 min) was combined with beraprost (100, 200 or 300 ng/kg/min for 60 min) or aspirin (35 mg/kg bolus i.v. before rt-PA infusion). The reperfusion time did not differ among the 4 groups. The time from reperfusion to reocclusion (one cycle) in the rt-PA plus beraprost 200 ng/kg/min group was significantly longer than the rt-PA alone group (40 +/- 8 min vs. 9 +/- 2 min, P < 0.05) and the recanalization duration calculated as the mean time from reperfusion to reocclusion in each cycle was prolonged in the rt-PA plus beraprost 200 ng/kg/min group compared with the rt-PA alone group (48 +/- 6 min vs 18 +/- 5 min, P < 0.05) and the reocclusion time and recanalisation duration tended to be elongated in the rt-PA plus beraprost 300 ng/kg/min group, whereas those were not altered by aspirin and 100 ng/kg/min of beraprost. Bleeding time was slightly prolonged and ex vivo platelet aggregation was slightly depressed by beraprost and aspirin. Systemic blood pressure was lowered with higher doses of beraprost. Beraprost sustained coronary reperfusion time and recanalization duration at the higher doses with an optimal level, but could not eliminate reocclusion completely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463005 TI - Right aortic arch with aberrant retroesophageal innominate artery: a report of 2 cases and review of the literature. AB - We describe two patients of right aortic arch associated with aberrant retroesophageal innominate artery. One case was associated with tetralogy of Fallot and a tortuous left common carotid artery originating from the retroesophageal innominate artery. Tetralogy of Fallot associated with this kind of aortic arch anomaly has never before been reported. The other case was associated with a perimembranous ventricular septal defect. Symptoms such as dyspnea, dysphagia and recurrent respiratory infection due to the compression by the vascular anomaly were not noted in these two cases. The morphological findings are indicative of a double aortic arch with an interruption of the left arch proximal to the common carotid artery. PMID- 8463006 TI - Acute myocardial infarction treated with intravenous streptokinase: 6-year follow up. AB - Our objective was to investigate variables which, although occurring during the acute period, could influence the medium (1st year) and long-term (6th year) survival of infarcted patients. Of a total of 332 patients treated consecutively and prospectively according to the same protocol which included intravenous streptokinase, 305 survived the hospital phase and represent the study population. Mean patient age was 55.6 +/- 10 years and mean follow-up time was 3.33 years, with 1008.59 patient-years. The clinical course of the group was analyzed according to the following variables: left ventricle ejection fraction, hypotension per/peri streptokinase infusion, CK-MB peak, previous myocardial infarction, number of obstructed coronaries, reinfarction, sex, 'definitive' treatment, residual obstruction, age, pain/streptokinase infusion interval, patency of the 'culprit' coronary and infarct location. Overall, patient survival was 93.8 +/- 1.4% during the 1st year and 83.7 +/- 2.6% at the 6th. The following groups showed significantly different (log-rank) survivals: (a) 1st year: 94.6% for absence and 82.6% for presence of reinfarction (P = 0.0451); 97.9% for inferior and 91.4% for anterior infarct location (P = 0.044); 96.4% for ejection fraction > 50% and 90.6% for ejection fraction < or = 50% (P = 0.0187); 96.5% for angioplasty/surgery and 90.1% for clinical treatment (P = 0.0028); 95.5% for absence and 80.6% for presence of previous infarct (P = 0.0001). (b) 6th year: 88.3% for ejection fraction > 50% and 73.9% for ejection fraction < or = 50% (P = 0.028); 87.4% for < or = 65 and 66.4% for > 65 years (P = 0.0114); 89.6% for aggressive and 76.8% for conservative treatment (P = 0.013); 86.6% for absence and 60.7% for presence of previous infarct (P = 0.0009). PMID- 8463007 TI - Functional significance of coronary collateral vessels in patients with previous 'Q' wave infarction: relation to aneurysm, left ventricular end diastolic pressure and ejection fraction. AB - The importance of coronary collateral circulation in relation to the left ventricular function, aneurysm formation and size was investigated in 100 patients with previous 'Q' wave myocardial infarction who underwent coronary angiography. Aneurysms were present in 20% of patients. The majority of these (80%) patients had severe or total occlusion of the left anterior descending artery. Thirty four percent of patients without aneurysm had significant collaterals whereas 25% of patients with aneurysms had collaterals (P > 0.05). However, the size of the aneurysm was smaller when adequate collateral circulation was present (Collateral Index 2 or above). The incidence of hypertension and diabetes was similar in both groups. Collateral circulation was more frequently seen in the anterior (60%) as compared to inferior myocardial infarction (40%), but Collateral Index was higher in right coronary artery disease. The number of patients with an elevated left ventricular end-diastolic pressure (> 12) or poor ejection fraction was similar in the two groups with and without collaterals. Thus, there was no beneficial effect of collateral circulation on left ventricular function. The incidence of aneurysm was not significantly lower, although the size of the aneurysm was significantly smaller in the presence of collateral circulation. PMID- 8463008 TI - Atrio-ventricular regurgitations in constrictive pericarditis: incidence and post operative outcome. AB - We studied 33 surgically proven cases of constrictive pericarditis during the period 1989-1991 by color Doppler echocardiography and angiography to look for incidence and postoperative outcome of atrioventricular regurgitation. The mean age was 27.2 + 16.5 years (21 males, 12 females). There was a very high incidence of mitral (79%, trivial in 13, mild in 11 and moderate in 2) and tricuspid (73%, trivial in 7, mild and moderate in 6 each and severe in 5) regurgitation. There was good correlation between 'color Doppler' and angiography for detection and quantification of these regurgitations (r = 0.89 for mitral and 0.76 for tricuspid regurgitation, respectively). There were no preoperative clinical or hemodynamic predictors for the incidence or severity of these regurgitations. Immediate postoperative (7-10 days) evaluation by color Doppler did not show any change in these regurgitations. A follow-up study (by color Doppler and angiography) in 18 patients at a mean period of 229 + 105 days revealed regression of these regurgitations by at least 1 grade in 50% of patients. Patients with persisting regurgitations had persisting hemodynamic abnormality and relatively longer duration of symptoms. The presence of atrio-ventricular regurgitations should not be taken as evidence favoring diagnosis of restrictive cardiomyopathy and against that of constrictive pericarditis. The mechanism of these regurgitations is not clear to us. PMID- 8463009 TI - Occlusive arterial disease of the hand due to repetitive blunt trauma: a review with illustrative cases. AB - OBJECTIVE: to increase clinical awareness of the role of repetitive blunt trauma, often occupational, in the development of occlusive arterial disease of the hand. STUDY DESIGN: illustrative cases are presented to emphasize the varied etiology and clinical features of occlusive arterial disease of the hand resulting from repetitive blunt trauma and an historical review of the literature is presented. RESULTS: Occlusive arterial disease of the hand due to repetitive blunt trauma is a common but often preventable disorder. The superficial location of many of the arteries of the hands and digits plus their close proximity to the bones of the hand makes them uniquely susceptible to injury from repetitive blunt trauma. An ever increasing number of occupations and leisure activities have been causally related to occlusive arterial disease of the hand. The diagnosis of occupational occlusive arterial disease due to blunt trauma is suggested by eliciting a history of repetitive blunt trauma to the hand in a patient with symptoms and/or signs of digital ischemia. The dominant hand is most commonly involved, but the non-dominant hand or both hands are affected in certain occupations. Possible predisposing or aggravating factors include tobacco use and working in a cold environment. The diagnosis of occlusive arterial disease confined to the hand or digits is confirmed by non-invasive studies in the vascular laboratory and demonstrated by arteriography. Conservative measures and protection of the hand from further trauma is sufficient for most patients, with surgical therapy being reserved for patients refractory to medical therapy or those with more severe ischemia. CONCLUSION: occlusive arterial disease of the hand may be more common than formerly thought and is often preventable by the proper use of hand tools or instruments and hand protection. This is another type of occlusive arterial disease in which tobacco may be a predisposing or aggravating factor. PMID- 8463010 TI - Late onset atrioventricular nodal tachycardia. AB - AV nodal tachycardia may present at any age, but onset in late adulthood is considered uncommon. To evaluate whether onset of AV nodal tachycardias at older age is related to organic heart disease (possibly setting the stage for re-entry due to degenerative structural changes) 32 consecutive patients with symptomatic AV nodal tachycardia were studied. The age at onset of attacks showed a bimodal pattern, with 2 peaks: one between 15 and 35 years (22 patients) and one around 55 years (10 patients). Significantly more older patients had an underlying heart disease (60% versus 14%, P < 0.01), with coronary artery disease in 4 and hypertensive heart disease in 3. Frequent supraventricular ectopic activity was seen during baseline 24-h ambulatory monitoring in all the older patients, versus in only half of the younger patients (P = 0.005). These results indicate that late onset AV nodal tachycardia (i.e. > age 45 years) is not infrequent (33%). The frequent supraventricular arrhythmias on one hand and age-related structural AV nodal changes, potentially enhanced by underlying heart disease on the other, both may contribute to the development of late onset re-entrant AV nodal tachycardia. PMID- 8463011 TI - Carotid sinus hypersensitivity abolished by aminophylline. AB - A 56-year-old patient with syncope due to carotid sinus hypersensitivity is presented. Carotid massage-induced sinus arrest was completely abolished by intravenous aminophylline. PMID- 8463012 TI - Incidence of atrioventricular block and chronic atrial flutter/fibrillation after implantation of atrial pacemakers; follow-up of more than ten years. AB - The incidence of atrioventricular (AV) block and chronic atrial flutter/fibrillation was determined in 41 patients, mean age 62.2 years (22 to 88 years) who received atrial pacemakers before October 1980. The mean follow-up period was 12.3 years, range 11-14.4 years. Twenty-five patients suffered from bradycardia-tachycardia syndrome, 13 symptomatic bradycardia, and 3 bradycardia related ventricular tachycardia. At follow-up: 18 patients (44%) had permanent I AV block; 11 patients had II-AV block, 9 patients (22%) transient Wenckebach block and 2 patients (5%) transient Mobitz block, all asymptomatic. The cumulative incidence of III-AV block was 1 (2.5%). Chronic atrial flutter/fibrillation occurred in 6 patients (15%), 5 were not pacemaker dependent; 1 received a ventricular pacemaker. Seventeen patients died after a mean of 7 years (0.6-12.2 years). Cumulative survival rate of 58% for 14.4 years, did not differ from a matched cohort of the normal population. There were no pacemaker related deaths. We conclude that long-term atrial pacing was safe and effective. The incidence of III-AV block and chronic atrial flutter/fibrillation was low. PMID- 8463013 TI - Longitudinal transgastric echocardiographic views utilizing a single-plane probe: anatomic correlations and clinical applications. AB - In order to widen the diagnostic capability of single-plane transesophageal echocardiography, which has been so far confined to transverse imaging planes, we obtained four transgastric longitudinal echocardiographic views which have not been previously described. These views can image structures such as superior and inferior vena cava, the right ventricular inflow and outflow tract, the mitral apparatus and the ascending aorta, which are poorly visualized by transesophageal transverse single-plane echocardiography. Among 400 consecutive patients these scans gave relevant additional diagnostic information in 62 cases (15.5%) and provided the correct diagnosis in 37 (9.2%). There were no complications related to the longer gastric manipulation of the probe and the quality of the images was high. We conclude that longitudinal echotomographic scanning of the heart is not exclusively confined to the use of biplane or omniplane probes, but longitudinal views can be consistently obtained with a single-plane instrument. PMID- 8463014 TI - Long-term echocardiographic evaluation of closed and open mitral valvulotomy. AB - From 1968 to 1989, 280 patients with post-rheumatic pure mitral stenosis underwent surgical commissurotomy; 134 a closed and 146 an open technique. Follow up exceeded 15 years in 56.7% of the patients. Echocardiographic analysis was performed in 120 patients and disclosed a larger mitral valve area in patients who underwent open valvulotomy (1.9 +/- 0.5 cm2 vs. 1.5 +/- 0.4 cm2 for the closed technique, P < 0.0002). On the other hand, considering the occurrence of post-surgical mitral regurgitation at a level greater than, or equal to moderate, open valvulotomy produced less favorable results (18.5% vs. 5% for the closed technique, P < 0.01). PMID- 8463015 TI - Balloon dilatation of a bioprosthetic pulmonary valve. AB - A 37-year-old man with stenosis of a bioprosthetic pulmonary valve underwent percutaneous balloon valvoplasty. After the procedure the patient had moderate pulmonary regurgitation which has been well tolerated. The patient remains well with good functional capacity on follow-up at 2 years. Percutaneous balloon dilatation may be effective as a palliative procedure in the management of stenosis of a bioprosthetic valve in the pulmonary position. PMID- 8463016 TI - Anomalous origin of the left pulmonary artery from the aorta in an adult as an isolated anomaly: a case report. AB - The rare occurrence of anomalous origin of the left pulmonary artery in an adult as an isolated malformation and normal pressures in the pulmonary artery arising from the right ventricle are described. The possible implications of surgery are also discussed. PMID- 8463017 TI - Apical hypertrophic cardiomyopathy presenting as acute subendocardial myocardial infarction. AB - Two patients with apical hypertrophic cardiomyopathy presented with angina at rest and giant inverted T waves in precordial leads on the electrocardiogram. At cardiac catheterisation one patient had mild coronary artery disease, the other had normal coronary arteries. In both, there was a systolic pressure gradient between the apex and main left ventricular cavity exceeding 100 mmHg. The presence of rest angina with the electrocardiographic findings lead to a mistaken, initial diagnosis of acute subendocardial myocardial infarction. PMID- 8463018 TI - Garlic--the other side of the coin. PMID- 8463019 TI - Alcohol, tobacco, and father's aggressive behavior in relation to socioeconomic variables in Cretan low versus medium income families. AB - In order to identify socioeconomic factors affecting parents' alcohol and cigarette consumption and father's aggressiveness toward other family members, 87 low-income and 92 medium-income Greek families were tested. Father's alcohol consumption correlated positively with his smoking (p < .0008) and aggressive behavior (p < .00005), while mother's alcohol correlated positively with her smoking (p < .0001) and number of marriages (p < .01), and negatively with the family's overcrowding index (p < .006). Furthermore, father's smoking correlated positively with his alcohol (p < .01), and mother's smoking with her alcohol (p < .0004) and tenancy (p < .01). Finally, father's aggressiveness was found to be positively related to his alcohol consumption and negatively to his work and level of education. PMID- 8463020 TI - Methodological issues in surveying older persons concerning drug use. AB - Despite beliefs that surveys involving older persons are less valid than those with other groups (due to memory loss, etc.), empirical verifications do not support this. Certain factors related to reduced validity must be considered (e.g., little education) and the confounding factors of cohort and time of measurement must be evaluated. Persons presumably suffering from dementia and institutional residents may be needlessly excluded. Methods suggested for improving validity include: sampling techniques, proxy respondents, administration and instrumentation, and interviewer variables. It is important to cross-validate data from surveys by using several concurrent methods. Instruments developed with younger subjects may be inappropriate or invalid with elders. PMID- 8463021 TI - Vulnerabilities and cultural change: drug use among Puerto Rican adolescents in the United States. AB - The investigations examined drug usage-based and culture-based differences in young Puerto Ricans living in New York (100 nonusers and 192 drug users), Americans living in New York (100 nonusers and 99 drug users), and Puerto Ricans living in Puerto Rico (100 nonusers and 98 drug users). The Associative Group Analysis method was used to measure cultural change in three dimensions: dominant perceptions, priorities, and evaluations. The findings show that the Puerto Rican drug user and nonuser groups in New York differed significantly in their paths of acculturation. The nonusers were shown to progress successfully in learning American meanings and adopting American perspectives and cultural norms. The drug users were attracted to dominant American priorities (e.g., wealth and freedom) but showed little progress in adopting deeper American cultural meanings necessary for effective coping. PMID- 8463022 TI - Alcohol consumption, low birth weight, and preterm delivery in the National Addiction Survey (Mexico). AB - In 1988 the Mexican General Directorate of Epidemiology and the Mexican Institute of Psychiatry carried out the first National Addiction Survey that provided prevalence estimates at national and regional levels of alcohol consumption, tobacco smoking, and several other drugs use. In addition, a questionnaire included questions regarding alcohol consumption during pregnancy and adverse outcomes. According to the results of logistic regression, women classified as suffering from Alcohol Dependence Syndrome had a very high risk of low birth weight and/or preterm delivery: Odds ratio = 12.1 with a 95% confidence interval of (1.3, 108.9) and p = .026. After controlling for several confounding variables, the findings remained basically the same. PMID- 8463023 TI - Lay beliefs about the causes and consequences of smoking cessation maintenance. AB - Descriptive research has corroborated the Relapse Prevention (RP) model of smoking relapse, but RP interventions have been generally ineffective. This discrepancy might arise from disagreement between the theory and ex-smokers' beliefs about what determines successful maintenance. We therefore asked 100 recent ex-smokers why they believed they would (or would not) be able to abstain for the following year, and what benefits they anticipated if they did. Modal responses were that personal attributes (e.g., willpower) would determine maintenance and that improved physical health would be its most important result. Twelve-month continuous abstinence was more common among those anticipating improved feelings of psychological or physical well-being than among those anticipating a reduction in problems or a diffuse health benefit. PMID- 8463024 TI - Interpersonal influences in college students' initial use of alcohol and drugs- the role of friends, self, parents, doctors, and dealers. AB - The use of alcohol and drugs by 1,711 college students was surveyed anonymously, with a special interest in determining the sources of influence that led them to the initial use of different substances. Depending on the chemical, friends, parents, the person himself or herself, and doctors were named as the initial introducers. Drug dealers, by contrast, were named rarely and only in connection with a few hard drugs. Factors influencing drug use are discussed, and suggestions for prevention and treatment are made. PMID- 8463025 TI - Neuromuscular fatigue and recovery in male and female athletes during heavy resistance exercise. AB - To examine neuromuscular fatigue and recovery ten male and nine female athletes performed a strenuous heavy resistance exercise protocol. The subjects strained their leg extensor muscles with the same maximal relative intensity by performing one maximal squat-lift with a load of 100% of 1 RM (one repetition maximum) 20 times (20 x 1 x 100%). Maximal voluntary neural activation (integrated EMG), maximal bilateral isometric force, force-time and relaxation-time curves of the leg extensor muscles were measured before and immediately after the exercise session as well as after resting for 1 hour, 2 hours, 1 day and 2 days. The session resulted in considerable gradual decreases in maximal force in the males by 24.1 +/- 14.4% (p < 0.001) and in the females by 20.5 +/- 11.8% (p < 0.01) as recorded immediately after the session. Significant (p < 0.05-0.01) decreases also took place in the males in the maximal IEMGs of the exercised muscles, while the corresponding decreases in the females were minor. The force-time curve shifted greatly to the right both in the males (p < 0.001) and in the females (p < 0.01) but the average change of 27.8 +/- 13.8% in the males was greater (p < 0.05) than that of 18.7 +/- 8.3% recorded for the females. The time of force relaxation lengthened (p < 0.05) in both groups. Maximal force recovered during the first hour of rest was more (p < 0.05) in the females than in the males but thereafter the recovery took place gradually in both groups to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463026 TI - Cardiorespiratory responses to exercise training in septuagenarian women. AB - Cardiorespiratory responses to a 12wk moderate exercise training program were examined in 30 sedentary elderly women (mean age = 73.6 +/- 0.7 yr). In addition, 12 highly conditioned (HC) older women (mean age = 72.5 +/- 1.8 yr; 11.2 +/- 1.2 yr training; 1.6 +/- 0.2 hr.d-1 aerobic activity) were tested at baseline for cross-sectional comparisons. The VO2max and VEmax of the HC subjects were 67% and 36% higher, respectively, (p < 0.001) than the combined sedentary subjects at baseline. Sedentary subjects were randomly assigned to a walking (WALK) or calisthenics control (CAL) group. The WALK group exercised 5 d.wk-1 for 30-40 min per session at 60.0 +/- 1.9% heart rate reserve while the CAL group engaged in mild musculoskeletal exercise. The WALK group demonstrated significant improvement in VO2max compared to CAL subjects at 12 wk (12.6% vs 2.2%, F = 5.74, p = 0.005). These data show that septuagenarian women demonstrate significant improvement in maximal cardiorespiratory fitness through moderate exercise training. PMID- 8463027 TI - Maximal aerobic power in cycle ergometry in middle-aged men and women, active in sports, in relation to age and physical activity. AB - Reliable standards of maximal power output in middle-aged and physically active men and women are desirable in sports-medical practice. For this purpose maximal cycle ergometer tests were evaluated in 2038 men and 898 women over 40 years of age (46.8 +/- 6.1 years (mean +/- SD) and 47.5 +/- 6.6 years), who volunteered in a sports-medical check-up and all of whom were active in sports for at least three months in the year preceding the screening (4.3 +/- 3.1 hours/week respectively 3.6 +/- 2.5 hours/week). The range of maximal values for power output (Wmax), heart rate (HRmax), systolic blood pressure (SBPmax) and peak plasma lactate concentrations (PPLa) during progressive cycle ergometer testing are presented for males and females who were divided into groups with a 5-years age difference. Wmax varied with sex (male = 1, female = 0), age (year) and height (cm); Wmax = 65.3 x (sex) + 2.0 x (height) -1.9 x (age) - 67.9 (See = 38.2; r = 0.76). The weighing of different factors that influence performance was also studied by multiple regression analysis to provide improved precision in standards used to interpret exercise tests. In both men and women about half of the variation of Wmax could be explained by the independent variables age, body mass, body fat, smoking habits, vital capacity, heart rate, and physical activity parameters. It is concluded that active involvement in endurance sports and/or the use of the bicycle for transport, contributed substantially to cardiovascular fitness in healthy, middle-aged men and women. PMID- 8463028 TI - Physiological comparison of roller skating, treadmill running and ergometer cycling. AB - This study was undertaken to determine the metabolic and cardiorespiratory differences between treadmill running, ergometer cycling and roller skating in top level roller skaters. The subjects performed 3 discontinuous graded tests until exhaustion. The protocol was established so that heart rate kinetics during exercise were similar in all the tests. Maximal oxygen uptake (VO2max), maximal heart rate and exercise time to exhaustion were higher during running (p < 0.05) than during cycling. Blood lactate during submaximal and maximal running exercise was significantly lower (p < 0.05) than during cycling or roller skating. There were no differences between cycling and roller skating in any of the variables studied. These results seem to suggest that, compared with running, VO2max during cycling is limited more by local muscle fatigue than by cardiac factors. The similar response found during roller skating and cycling supports the concept that cycloergometer testing is a valid simple laboratory test for testing physical fitness in top level roller skaters. PMID- 8463029 TI - Reduction of postprandial lipemia after acute exposure to high altitude hypoxia. AB - The effects of acute exposure to high altitude hypoxia upon plasma levels of lipids and lipoproteins were studied in 6 healthy subjects observed under strict dietary control. Fasting and postprandial values, first measured at low altitude (< 300 m), were compared to values measured 7 days after transfer by helicopter to the Observatoire Vallot (4350 m) near Mont-Blanc. Plasma levels of catecholamines and thyroid hormones were measured in parallel. Under normoxic conditions, a rise in plasma levels of cholesterol, triglycerides and phospholipids was found 4 hr after the test-meal, whereas circulating norepinephrine fell. Under hypoxic conditions, postprandial effects on lipid parameters disappeared, lipemic responses to the test-meal were dramatically reduced and plasma levels of norepinephrine increased. These effects were accompanied by a fall in triglyceride-rich lipoproteins, generally associated with a slight elevation of HDL-cholesterol, especially the less dense HDL2 fraction. When all results obtained in normoxic and hypoxic conditions were analyzed together, a series of highly significant correlations were found between the magnitude of postprandial lipidemia and various lipid parameters, in particular HDL2-cholesterol which was negatively correlated. These observations strongly suggest that high altitude hypoxia, independent of interfering variables such as exercise training or cold exposure, induced a net stimulation of the lipolysis of plasma triglycerides. PMID- 8463030 TI - The effect of chronic and acute exercise on immunity in rats. AB - The effects of exercise training and acute exercise on the immune system were investigated in rats. For chronic exercise training, the rats ran on a drum exerciser at the intensity of about 60-70% of maximal oxygen consumption (VO2max) for 30 min and then extended up to 60 min per day, 5 days per week for 10 weeks. The rats were at rest for 3 days before sacrifice. The mitogenic activity of spleen lymphocytes to concanavalin A (Con A) and staphylococcal enterotoxin B (SEB) decreased as compared to the sedentary control, while proliferative response to lipopolysaccharide (LPS) increased. The interleukin-2 (IL-2) production in the training group was reduced. The immunomodulatory effect after acute exercise has also been investigated and it showed profound enhancement of cell proliferation to Con A, SEB and LPS in mild (50% VO2max for 10 min) and moderate (70% VO2max for 10 min) exercise groups. The enhancing activity was less prominent after severe exercise (> 75%) VO2max until exhaustion). The IL2 production increased in all of these acute exercise groups. Nevertheless, there was no significant variation between exercise and control groups in the cell number per spleen and the percentages of various lymphocyte populations, i.e., total T, CD4+, CD8+ and IL-2R+ T cells as well as B cells. In summary, this study indicates that chronic exercise training may cause the reduction of T cell activity while acute exercise manifests an enhancing effect. However, B cell proliferation was elevated in both chronic and acute exercise groups. PMID- 8463031 TI - The associations between family history of coronary heart disease, physical activity, dietary intake and body size. AB - Physical activity has been associated with coronary heart disease (CHD) as well as several CHD risk factors. In this study, we examine the association of a positive family history of CHD and physical activity on dietary intake and body size indicators among 891 healthy young adults (18 to 39 years of age) and 471 older adults (40 to 83) observed between 1980 and 1986. Participants reported the number of times per week they walked and/or jogged one mile, biked three miles, participated in sports, or performed other intense activities. Older men with a family history of CHD reported more physical activity than men without a family history of CHD (60% compared to 28.6%; p = 0.002). Younger women without a family history of CHD reported more physical activity than women with a family history of CHD (30.2% compared to 15.9%; p = 0.004). Fruit and vegetable intake increased with increasing levels of physical activity in younger adults. The only dietary association with family history was higher levels of fatty foods reported among older women with a family history versus those without a family history (p = 0.03). Young women with a family history of CHD were more likely to have higher BMI levels at all levels of physical activity and a higher percent of their ideal body weight per unit of physical activity (p = 0.01). For instance, young women who were most active with a family history of CHD were at 115% of their ideal body weight, while those without a family history were at 110.2% of their ideal body weight. There were no significant interactions between physical activity and CHD family history in this population. These findings suggest that family history of CHD alone may not be adequate to stimulate one to adopt a more healthy lifestyle. PMID- 8463032 TI - Embryologic clues to human yolk sac tumors: a review. AB - Morphological similarities and differences in the developmental structure of the human yolk sac and human yolk sac tumors (HYSTs) are reviewed to determine the histogenesis of the currently recognized multiple tumoral patterns. Although many equivalent histochemical markers, secretory hyaline globules, and hemopoiesis occur in both HYSTs and the secondary human yolk sac (SHYS), few similarities are found in their comparative morphology. For example, HYSTs do not reproduce the characteristic morphology of SHYS with its large, clear cells and endodermal and intracellular tubules; basement membrane is abundant in tumors but only an inapparent and temporary structure in the SHYS; no Schiller-Duval sinuses are found in either primary or secondary human yolk sacs, and the plentiful mesenchymal (mesoblastic) components of tumors are absent in the SHYS except for the collagenous connective tissue that occurs during regression. Unlike the SHYS, which is a terminal structure incapable of polydifferentiation and only rarely develops any somatic structures, HYSTs frequently differentiate tissues of endodermal origin such as intestine, liver, and even lung. The primary human yolk sac is capable of multiple differentiation, both endodermal and possibly mesenchymal, as well as its ultimate differentiation into the SHYS with its characteristic endodermal markers. Thus, it seems more appropriate to correlate the comparative morphology of HYSTs with the primary human yolk sac, rather than the SHYS, and, in the light of this, reconsider their classification as extraembryonally differentiated tumors. PMID- 8463033 TI - Tumor-like lesions of the ovary associated with pregnancy. AB - Six nonneoplastic ovarian lesions (or alterations) are associated with pregnancy or the puerperium, each of which can simulate a neoplasm on clinical, gross, or microscopic examination. These lesions include pregnancy luteoma, hyperreactio luteinalis, large solitary luteinized follicle cyst of pregnancy and puerperium, intrafollicular granulosa cell proliferations, hilus cell hyperplasia, and ectopic decidua. Because these lesions involute spontaneously after termination of pregnancy or are adequately treated by a conservative surgical approach, unnecessarily radical operations can be avoided if the correct diagnosis is made by the pathologist. PMID- 8463034 TI - Differential diagnosis of peritoneal lesions of mullerian type and similar epithelial tumors of the peritoneum. AB - The female peritoneum is the site of various tumor-like and tumorous lesions that resemble derivatives of the primary mullerian system. Those lesions can therefore be summarized under the term secondary mullerian system. These lesions can cause problems in macroscopic and microscopic examination if clinicians or pathologists are not acquainted with them. The relationship between the derivatives of the embryonal mullerian duct and the secondary mullerian system is underscored by the expression of many different antigens, as revealed by immunohistology. PMID- 8463035 TI - The behavior of serous tumors of low malignant potential: are they ever malignant? AB - Although the literature describing the clinicopathologic features of serous borderline or low malignant potential (LMP) tumors of the ovary is extensive, the behavior of these neoplasms is not well understood. While some studies indicate a 30 to 40% mortality for advanced stage tumors, it is not clear whether this poor outcome is related to "benign" complications of the disease, such as bowel obstruction from adhesions, or to development of carcinomatosis from malignant transformation. In an effort to determine more clearly the cause of death of patients with serous LMP tumors and to assess the malignant potential of these tumors, defined by progression to invasive serous carcinoma, we reviewed 22 series, totalling 953 patients. Analysis of these studies reveals that for patients with stage I tumors, survival is 99%. For advanced stage disease, survival is 92%. Advanced-stage tumors associated with so-called invasive implants were excluded from this analysis because they were considered invasive serous carcinomas at the time of diagnosis rather than noninvasive LMP tumors. Various causes of death in patients with advanced-stage tumors include complications of the disease, complications of therapy, and, rarely, malignant transformation. Our review of 953 cases disclosed only seven (0.7%) tumors that appeared to have undergone malignant transformation, resulting in death from intraabdominal carcinomatosis. Because the rate of malignant transformation is exceedingly low and because classifying these tumors as malignant often leads to unnecessary treatment, we believe that the term low malignant potential or borderline tumor is not justified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463036 TI - Ovarian Brenner tumors and transitional cell carcinoma: recent developments. AB - Brenner tumor variants--such as metaplastic, proliferating, and low-malignant potential (three categories recently designated as intermediate Brenner tumors)- and malignant Brenner tumors are unusual tumors presenting problems in classification. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low-malignant-potential Brenner tumors. The category of "transitional cell carcinoma of the ovary" has been proposed for those primary ovarian carcinomas in which definite urothelial features are present, but no benign, metaplastic, and/or proliferating Brenner tumor is identified. Two subtypes have been described, the papillary and the malignant Brenner-like types. These tumors are more aggressive than malignant Brenner tumors, but they appear to respond better to chemotherapy than other types of ovarian epithelial cancer. PMID- 8463037 TI - Proliferative endometrioid tumors and endometrioid tumors of low malignant potential of the ovary. AB - Endometrioid epithelial tumors occur as adenofibromas, proliferative endometrioid tumors, endometrioid tumors of low malignant potential, and endometrioid carcinoma. Criteria for each category are given. Proliferative endometrioid tumors are benign, and the low-malignant-potential ones seldom, if ever, metastasize; they should not be designated carcinomas or regarded as malignant. However, invasive carcinoma may arise in both, and both may be associated with a similar tumor outside ovary, the latter a result of either a second primary neoplasm or rupture of the primary ovarian tumor. Endometrioid tumors of low malignant potential do not need a staging procedure. Their behavior is more akin to that of Brenner and mucinous tumors of low malignant potential than to that of serous tumors of low malignant potential. Vague terms such as "malignant adenofibroma" and "borderline endometrioid tumor" have been attached to a variety of intermediate endometrioid neoplasms and should be dropped in favor of more specific designations defined by semiquantitative criteria. PMID- 8463038 TI - Sertoli-Leydig cell tumors of the ovary: review with emphasis on historical aspects and unusual variants. AB - Among the many contributions to gynecological pathology of Dr. Robert Meyer were his observations on Sertoli-Leydig cell tumors and the formulation of a classification of them that is the basis of the one used today. Selected variants in this category of tumors are reviewed here. Sertoli cell tumors are of interest clinically because, in contrast to other tumors in this category, they tend to be estrogenic rather than androgenic. They are important for the pathologist to be aware of, because other neoplasms of diverse types may mimic them. Heterologous Sertoli-Leydig cell tumors are noteworthy; since they may feature mucinous epithelium, carcinoid, skeletal muscle, and/or cartilage, they may present a confusing histologic picture that could result in a misdiagnosis. Similarly, the recently recognized retiform variant of Sertoli-Leydig cell tumor is apt to be misdiagnosed because its pattern of slit-like glandular spaces and papillae is often confused with tumors in the common epithelial category. These retiform lesions are also less often androgenic than are other Sertoli-Leydig cell tumors. Finally, neoplasms with bizarre nuclei and tumors that occur in pregnancy, which often have prominent intercellular edema, are briefly discussed. PMID- 8463039 TI - Pathology of early malignant change in the ovary. AB - Our scanty knowledge of the pathology of early malignant change in the ovary is reviewed. The concept of ovarian intraepithelial neoplasia is discussed, and the malignant potential of ovarian cystadenomas is considered. The question of overt malignant change in tumors of borderline malignancy is reviewed. It is concluded that any advance in our understanding and our knowledge of the early stages of malignant change in the ovary will only come from the use of newer techniques that allow a more sophisticated approach than that allowed by purely morphological methods. PMID- 8463040 TI - Prognostic markers in epithelial ovarian cancer. AB - Useful prognostic markers are available in certain areas of clinical management of epithelial ovarian tumors. CA125 and the flow cytometric determinants of DNA index and S-phase fraction are of obvious value in evaluating the outlook of patients particularly in stage II and more advanced cases as well as in the follow-up for recurrent disease. Combinations of other serological markers with CA125 add to the usefulness and may increase the proportion of stage I cases scoring positive with these tests. At the moment, none of the molecular biological markers associated with the oncogen and growth-suppressor gene derangement pathways can be used as candidates for screening markers. Development in this area is very rapid, however, and with increasing understanding of such key conceptual questions as the biological nature of the ovarian borderline tumors, more accurate prognostic markers will emerge. PMID- 8463041 TI - Diagnosis of endocrinally active ovarian tumors. AB - The preoperative localization of small occult ovarian or adrenal androgen secreting tumors is difficult. Selective sampling of glandular effluent by retrograde venous catheterization constitutes a reliable combined radiographic endocrine approach. Steroid gradients between peripheral and organ vein levels are suspicious of a tumor especially when the testosterone gradient is elevated, e.g. more than 2.7 ng/ml between ovarian and peripheral venous blood. Therefore, selective catheterization is currently the most sensitive method for detection of androgen-secreting tumors smaller than 1 cm in diameter. PMID- 8463042 TI - Histomorphometry of normal and abnormal endometrial samples. AB - One hundred forty samples of normal and pathological endometrium were examined morphometrically in order to achieve a discriminant function among normal and pathological diagnoses. Samples of proliferative and secretory normal endometrium, simple and atypical hyperplasia, and well-differentiated adenocarcinoma were included in this study. Morphometrical and stereological characteristics for both glands and lumina as well as epithelium were registered. Stepwise discriminant analysis was performed. There is an increase in size of glands from proliferative endometrium to well-differentiated adenocarcinoma. The stereological measurements parallel morphometrical measurements. The accuracy of diagnosis by morphometrical and stereological means were 91% when the normal group (proliferative and secretory phase) were included. Accuracy increases to 95% when only three pathological groups were used; only one simple hyperplasia and one well-differentiated adenocarcinoma were incorrectly diagnosed. In all functions, the volume density of epithelium was selected. The reproducibility on a new data set demonstrates an efficiency of 92, 87, and 100% for three discriminant analyses (five, four, and three diagnostic groups, respectively). PMID- 8463043 TI - Immunocytochemical study of insulin-like growth factor I and insulin-like growth factor I receptor in human endometrium during the normal menstrual cycle. AB - Our aims were to detect, using immunocytochemistry, IGFI and IGFI R in the human endometrium and to assess semiquantitatively their levels in the phases of the normal menstrual cycle. Twelve normal proliferative and 10 normal secretory endometrial samples were studied. Each specimen was subjected to an immunocytochemical peroxidase antiperoxidase protocol. The antibodies used to detect IGFI and IGFI R were, respectively, 3D1/2/1 and alpha 1R3. Analysis of variance (ANOVA) was performed to evaluate mean IGFI and IGFI R levels in the glandular epithelium and stroma of each sample while correcting for intra- and interobserver variation. These experiments show the presence of IGFI and IGFI R in human endometrium. There are significant variations in the IGFI and IGFI R levels from patient to patient within each cycle phase, and between glands and stroma within each sample. These findings highlight the importance of the use of in situ studies to clarify endometrial IGFI and IGFI R physiology. PMID- 8463044 TI - Natural history of cervical intraepithelial neoplasia: a critical review. AB - The literature dealing with the natural history of cervical intraepithelial neoplasia (CIN) since 1950 is reviewed, in particular from the viewpoint of regression, persistence, and progression. When stratified into the various grades of severity, the composite data indicate the approximate likelihood of regression of CIN 1 is 60%, persistence 30%, progression to CIN 3 10%, and progression to invasion 1%. The corresponding approximations for CIN 2 are 40%, 40%, 20%, and 5%, respectively. The likelihood of CIN 3 regressing is 33% and progressing to invasion greater than 12%. It is obvious from the above figures that the probability of an atypical epithelium becoming invasive increases with the severity of the atypia, but does not occur in every case. Even the higher degrees of atypia may regress in a significant proportion of cases. As morphology by itself does not predict which lesion will progress or regress, future efforts should seek factors other than morphological to determine the prognosis in individual patients. PMID- 8463045 TI - Tribute to Robert Meyer. PMID- 8463046 TI - The evaluation of type I and type II beta-turn mixtures. Circular dichroism, NMR and molecular dynamics studies. AB - Circular dichroism (CD) and 1H-(1H)NOE spectra were obtained for Piv-Pro-Ser NHCH3 (1), [Piv-(CH3)3-C-CO], Boc-Pro-Ser-NHCH3 (2) and Boc-Val-Ser-NHCH3 (3), to determine the solution conformation of these beta-turn models. In the crystal, 1 and 3 adopt an ideal type I beta-turn, while 2 is characterized by a semifolded backbone geometry incorporating a cis Boc-Pro tert-amide bond. The predominance of a beta-turn conformation in solution was suggested for models 1-3 on the basis of 1H-(1H)NOE data. In a nonpolar solvent the prevailing trans rotamer form (> 80%) of 2 has a beta-turn conformation according to heteronuclear NOE measurement. Positive 1H-(1H)NOEs were detected between the H alpha(Pro)/NH(Ser), H alpha(Ser)/NH(Ser) and NH(NHCH3)/HN(Ser) protons in the trans Boc-Pro rotamer form of 2 at -20 degrees in CDCl3. Similar positive homonuclear NOE enhancements were also observed on the appropriate proton signals in other models, such as Boc Val-Ser-NHCH3 (3), Boc-Val-D-Ser-NHCH3 (4) and Boc-Pro-D-Ser-NHCH3 (5), in various solvents. The 1H-(1H)NOE experiments carried out in CD3CN clearly showed that besides the type I (or III) beta-turn structure, one of the main conformations of models 1-5 is close to the type II beta-turn backbone geometry in a nonpolar solvent. Unexpectedly, the conformational mixture of models 1-3 were characterized by class C (helix-like) CD spectra, although class C spectra are generally only correlated with the type I beta-turn conformation. These acyclic models are the first carefully investigated examples of -L-L- triamide systems, containing a significant amount of a type II beta-turn, as well as the type I beta-turn and, however, yielding a class C circular dichroism spectra. The CD spectra recorded for 3 and 4 in acetonitrile were 'calibrated' using the 1H (1H)NOE data. Such a "calibration", as well as the semi-quantitative CD and NMR comprehensive analyses, demonstrated that class C, class B, as well as class C' CD spectra may be obtained from the linear combination of the same two-component spectra, with different conformational weights. Therefore, it is suggested that the extraction of the conformational components of such models, simply on the basis of their CD spectra, must be made with caution. PMID- 8463047 TI - Solid-phase peptide synthesis on proteins. AB - A new method for solid-phase peptide synthesis in which a protein is used as the solid support has been developed. Two aspects of the method have been demonstrated. The peptides H-Phe-Leu-Glu-Glu-Val-OH (1) and H-Leu-Leu-Ala-Gly-Val OH (2), respectively, were synthesized on the amino groups of BSA via a cleavable linker, using the Fmoc group protecting scheme. The free peptides were obtained by cleavage from the protein with 95% TFA, precipitation in diethyl ether and additional work-up by either dialysis or centrifugation through a membrane followed by gel filtration. The identity of the products was determined by amino acid analysis and HPLC. The peptide-protein conjugates, H-Ser-Met-Asp-Thr-Ser-Asn Lys-Glu-Glu-Lys-BSA (3) and H-Thr-Val-Leu-BTG (4), were obtained in the same manner, omitting the cleavable linker group. It was found that 35-50 peptide chains were conjugated per molecule BSA and BTG, respectively. Immunization of rabbits with conjugate 3 gave rise to peptide specific antibodies. This method will be useful for generation of sequence specific antibodies, since the peptide is conjugated to the carrier protein exclusively via its C-terminus, and will allow synthesis of highly specific peptide-protein conjugates. PMID- 8463048 TI - Comparison of GH-stimulation by GH-RH(1-29)NH2 and an agmatine29 GH-RH analog, after intravenous, subcutaneous and intranasal administration and after pulmonary inhalation in rats. AB - Many studies have shown that human GH-RH(1-29)NH2 possesses full intrinsic activity of GH-RH(1-44)NH2 in vitro and in vivo. This investigation was performed to evaluate the efficacy of GH-RH(1-29)NH2 given by different routes of administration in stimulating GH release in rats. In each case GH-RH(1-29)NH2 was administered intravenously, subcutaneously, intranasally and by pulmonary inhalation at two different doses to groups of seven males rats. At a dose of 150 micrograms/kg GH-RH(1-29)NH2, the magnitude of GH response was significantly higher for the pulmonary inhalation group (355 +/- 33.2 ng GH/mL) than for the subcutaneous group (246 +/- 36 ng GH/mL) or for the intranasal group (175 +/- 30 ng GH/mL). The group injected intravenously with GH-RH(1-29)NH2 at a dose of 2.5 micrograms/kg showed the highest response, GH levels reaching 877.2 +/- 115 ng/mL. A similar pattern of responses was obtained for the superactive GH-RH(1 29) agmatine29 analog, MZ-3-149, at doses that were 50 times lower. Our results indicate a high bioavailability of GH-RH(1-29)NH2 or analog MZ-3-149 administered by a convenient pulmonary inhalation route. The GH-releasing effect of GH-RH(1 29)NH2 or analog MZ-3-149 delivered by pulmonary inhalation is superior to subcutaneous and intranasal administration. PMID- 8463049 TI - Multiple column peptide synthesis, Part 2 (1, 2). AB - A manually operated apparatus for parallel multiple column soli-phase peptide synthesis is described. It employs Fmoc-amino acid-O-Dhbt or -Pfp esters in the continuous flow version of the polyamide method on small packed columns of kieselguhr supported resin in a reaction block of Teflon. The solvents and deprotecting reagents are dispensed from two washers in a parallel fashion and reagent consumption is low. Activated and protected amino acids are transferred from a dispenser tray as solutions, eight at a time. The use of the method is demonstrated by the synthesis of overlapping peptides from a protein structure and of analogous protease substrates. The products have been characterized by HPLC, FAB mass spectroscopy and amino acid analysis. PMID- 8463050 TI - Efficient solution phase synthesis and use of multiple O-phosphothreonyl containing peptides for calcium phosphate binding studies. AB - The protected phosphothreonine derivative Boc-Thr(PO3Ph2)-OH was prepared in high yield from Boc-Thr-OH by a simple three-step procedure which involved 4 nitrobenzylcarboxyl protection, either phosphorotriester (diphenyl phosphorochloridate) or "phosphite-triester" (diphenyl N,N diethylphosphoramidite) phosphorylation of the threonine hydroxyl group of Boc Thr-ONb followed by hydrogenolytic carboxyl deprotection. The three Thr(P) containing peptides, H-Thr(P)-Glu-Glu-NHMe.TFA, H-Thr(P)-Thr(P)-Glu-Glu-NHMe.TFA and H-Thr(P)-Thr(P)-Thr(P)-Glu-Glu-NHMe.TFA, were prepared in high yield by the use of Boc-Thr(PO3Ph2)-OH in the Boc mode of peptide synthesis (mixed anhydride method) followed by platinum-mediated hydrogenolytic deprotection of the Thr(PO3Ph2)-containing peptides. The use of the phosphopeptides in calcium phosphate binding studies showed that the triple Thr(P)-cluster was a basic structural requirement, since only the pentapeptide was able to bind calcium phosphate efficiently. PMID- 8463051 TI - Serine-containing 10-membered cyclodepsipeptides. Synthesis and molecular structure of PhCH2CO-DSer-Pro-Pro- and PhCH2CO-DSer-Pro-DPro-. AB - As a part of a research program aimed at studying synthesis and conformation of small ring peptides, the cyclization of diastereoisomeric N-phenylacetyl-seryl propyl-proline tripeptides has been examined. Two 10-membered peptide lactones, PhCH2CO-DSer-Pro-Pro- 5a and PhCH2CO-DSer-Pro-DPro- 5b, have been isolated by treating the corresponding linear p-nitrophenyl esters with DBU in dry benzene. In these two compounds the serine lactone fragment (a common structural feature of several bioactive cyclodepsipeptides) is inserted into a highly strained small ring system. The conformation in the crystal of 5a and 5b has been studied by X ray analysis. Both the 10-membered rings of 5a and 5b adopt an overall cis-cis trans conformation in which the lactone junction is trans. The deviations from planarity of the peptide units vary from delta omega = 30 degrees for the DSer Pro bond in 5b to delta omega = 5-6 degrees for the DSer-Pro bond in 5a and Pro DPro bond in 5b. The skeletal atoms of 5b, containing the Pro-DPro sequence, are related by a pseudo-symmetry mirror plane passing through the Pro carbonyl and the opposite DSer C beta H2 group. In both the molecules the exocyclic amide bond adopts an extended conformation with respect to the DSer-Pro ring junction; this arrangement gives rise to a C5-type ring structure which is well evidenced in the case of 5a. PMID- 8463053 TI - Suppression of tuftsin activity by the partial sequences of adenovirus type 2 proteins. AB - The synthesis of tuftsin inhibitor-like partial sequences of adenovirus type 2 proteins: TVPPR (1), TRPPR (2), TGPPT (3), PRPPT (4), FVPPR (5), ARPPA (6) and YGPPK (7) are described. The choice of peptides for synthesis was performed by using a simple computer-aided method for predicting antigenic determinants of proteins. For all these peptides an inhibitory activity against tuftsin was found. PMID- 8463052 TI - Synthesis and conformational studies on peptides corresponding to a putative autophosphorylation site of abl TPK. AB - The transforming gene of Abelson murine leukaemia virus (v-abl) codes for a membrane-associated tyrosine-specific protein kinase (abl TPK). Analysis of the v abl gene has shown that both the fibroblast-transforming and tyrosine-protein kinase activities reside within a minimal region encoding a protein of 43 kDa (p43v-abl), which represents the most active, isolated form of this enzyme. Since the cellular substrates for p43v-abl are yet to be identified, we synthesized by classical solution methods the octapeptide H-Gly-Asp-Thr-Tyr-Thr-Ala-His-Ala-OH, corresponding to the structural sequence of the main putative autophosphorylation site (Tyr 515) of the abl TPK, as well as some of its analogs modified in positions -2, -1, +1 and +3. The synthetic peptides were tested as substrates for the p43v-abl. The kinetic data obtained indicate that the rates of their phosphorylation vary considerably depending on the sequence of the peptide, as expected. As a rule, no significant increment of the efficiency results from each substitution in the parent sequence. While the replacement of the two charged residues, namely Asp-2 and His-7, with neutral Ala is well tolerated, the substitution with amino acids bearing opposite charges is detrimental. The correlation between secondary structure of our synthetic octapeptides and their substrate recognition by p43v-abl was studied using CD and fluorescence spectroscopy in 5 mM Tris, in 98% TFE/Tris and in 30 mM SDS solutions. The comparison of the spectroscopic data with the kinetic parameters does not confirm a close relationship between the conformational properties of these peptides and their enzymatic role. PMID- 8463054 TI - Acidolytic cleavage of tris(alkoxy)benzylamide (PAL) "internal reference" amino acyl (IRAA) anchoring linkages: validation of accepted procedures in solid-phase peptide synthesis (SPPS). AB - Under the normal conditions of acidolytic cleavage/deprotection of tris(alkoxy)benzylamide (PAL) anchoring linkages in Fmoc solid-phase peptide synthesis (SPPS), product release occurs by a straightforward single-step pathway. A recently reported cleavage of the NH--alpha CH bond of an amino acyl residue adjacent to PAL [see Int. J. Peptide Protein Res. 38, 146-153 (1991)] could not be confirmed in novel experiments incorporating a double "internal reference" amino acid (IRAA) design. The results of the present work revalidate the widely accepted application of IRAAs to monitor yields in SPPS, and confirm the reliability of PAL methodology for the preparation of C-terminal peptide amides. PMID- 8463055 TI - Nursing in Europe. AB - In the long and frequently troubled history of Europe a span of 20 years seems insignificant, but placed in context of a century and a half of modern nursing the last two decades have been rich in growth and significance for the profession. As a nurse privileged to work with colleagues from the EC member states over this period, I have witnessed a great "sea change" brought about by nurses' own efforts through close cooperation and trust. These nurses came from 12 very different countries but had a common link: membership with the International Council of Nurses (ICN). Nursing in Europe faces many daunting challenges but we have more things to unite us that to divide us. The following articles should convince the reader that this is indeed the case. PMID- 8463056 TI - Nursing's strategy in the European community. AB - The nursing profession in Europe has undergone tremendous changes over the past 20 years. Below, a look at the new face of European nursing and its principal actors: The Standing Committee of Nursing in the EC, the women's liberation movement and the Nursing Unit at the WHO European Office in Copenhagen, Denmark. PMID- 8463057 TI - How nurses can work with the EC Commission. AB - For nurses in the European Community it is important that their voice be heard in Brussels, particularly when new initiatives are being developed. Below, the author introduces nurses to the workings of the Commission. PMID- 8463058 TI - Free-lance nursing in Italy. AB - In 1987 Registered Nurses Ernesta 'Tina' Galli and Joanne Lindsay embarked on a unique venture--a private agency* organized and run by nurses that engages free lance nurses to fill the need for nursing assistance both at home and in public and private institutions. The response has been overwhelming. Today they have branches throughout Italy and have expanded their services to include research and primary health care. Below, their story. PMID- 8463059 TI - Regulation and the empowerment of nursing. AB - The International Council of Nurses (ICN) has been a vanguard for the regulation of nursing standards worldwide. In the European region ICN has organized three workshops at which nurses representing 14 countries* critically examined their national legislations and, with their respective nurses' associations, devised concrete plans to change the regulations where necessary in their respective countries. Compared with developing countries, the structures in the European countries are more established and resistant to change, thus making it more difficult for European nurses to break the hard-fast regulatory encasement. An area that has received special attention has been the regulation of nursing specialties, particularly issues relating to their identity and control. An active participant in ICN's European regulation workshops and chief executive of the UK's regulatory body for nursing and midwifery, Colin Ralph takes a stand for empowering the nursing profession through regulation and offers assistance to those who need help in developing nursing regulations, not only in Europe but worldwide. PMID- 8463060 TI - Biochemical correlates of long-term potentiation in hippocampal synapses. AB - Figure 2 summarizes biochemical events which are currently known or hypothesized to participate in LTP induction/maintenance. Current evidence strongly suggests that postsynaptic Ca2+, both entered from the outside of cells and released from intracellular stores, is the initial key substance for the induction of LTP. A rise of [Ca2+]i triggers a variety of enzymatic reactions and initiates the enhancement of synaptic transmission. This first step may be achieved by direct/indirect phosphorylations of protein molecules in postsynaptic receptors/ion channels. This would result in an increase in receptor sensitivity. An immediate increase in the number of available postsynaptic receptors by modifications of spine morphology is another candidate. Such modifications may be accomplished by cytoskeleton rearrangements or changes in extracellular environments. A change in spine structure may also cause an increase in spine neck conductance. Although it is unknown to what extent the increase in [Ca2+]i affects cellular chemistry, Ca2+ probably also directly/indirectly stimulates cascades which exert effects more slowly. A delayed increase in metabotropic receptor sensitivity may occur. New synthesis of protein molecules may be involved in late periods of LTP by replacing turnovered molecules and/or by supplying new materials. Some of these chains of biochemical events may also apply to presynaptic terminals, although the existence of retrograde messenger substances must still be confirmed. In addition, interactions between different protein kinases and second messengers appear to occur to bring about final effects. PMID- 8463061 TI - Striatal dopamine in reward and attention: a system for understanding the symptomatology of acute schizophrenia and mania. PMID- 8463062 TI - Acetylcholine transport, storage, and release. AB - ACh is released from cholinergic nerve terminals under both resting and stimulated conditions. Stimulated release is mediated by exocytosis of synaptic vesicle contents. The structure and function of cholinergic vesicles are becoming known. The concentration of ACh in vesicles is about 100-fold greater than the concentration in the cytoplasm. The AChT exhibits the lowest binding specificity among known ACh-binding proteins. It is driven by efflux of protons pumped into the vesicle by the V-type ATPase. A potent pharmacology of the AChT based on the allosteric VR has been developed. It has promise for clinical applications that include in vivo evaluation of the density of cholinergic innervation in organs based on PET and SPECT. The microscopic kinetics model that has been developed and the very low transport specificity of the vesicular AChT-VR suggest that the transporter has a channel-like or multidrug resistance protein-like structure. The AChT-VR has been shown to be tightly associated with proteoglycan, which is an unexpected macromolecular relationship. Vesamicol and its analogs block evoked release of ACh from cholinergic nerve terminals after a lag period that depends on the rate of release. Recycling quanta of ACh that are sensitive to vesamicol have been identified electrophysiologically, and they constitute a functional correlate of the biochemically identified VP2 synaptic vesicles. The concept of transmitter mobilization, including the observation that the most recently synthesized ACh is the first to be released, has been greatly clarified because of the availability of vesamicol. Differences among different cholinergic nerve terminal types in the sensitivity to vesamicol, the relative amounts of readily and less releasable ACh, and other aspects of the intracellular metabolism of ACh probably are more apparent than real. They easily could arise from differences in the relative rates of competing or sequential steps in the complicated intraterminal metabolism of ACh rather than from fundamental differences among the terminals. Nonquantal release of ACh from motor nerve terminals arises at least in part from the movement of cytoplasmic ACh through the AChT located in the cytoplasmic membrane, and it is blocked by vesamicol. Possibly, the proteoglycan component of the AChT-VR produces long-term residence of the macromolecular complex in the cytoplasmic membrane through interaction with the synaptic matrix. The preponderance of evidence suggests that a significant fraction of what previously, heretofore, had been considered to be nonquantal release from the motor neuron actually is quantal release from the neuron at sites not detected electrophysiologically.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463063 TI - Molecular neurobiology of dopaminergic receptors. AB - Table I summarizes the properties of all of the dopamine receptors that have been cloned to date. Thus far, five different genes encoding pharmacologically distinct receptors have been identified and isolated. Based on their structural, pharmacological, and functional similarities, two of these, D1A and D1B (or D1 and D5), comprise the D1 subfamily. D2, D3, and D4 receptors represent a D2 subfamily whose members are also structurally and pharmacologically similar. In fact, given these considerations, it has been suggested that the D2, D3, and D4 receptors be termed the D2A, D2B, and D2C receptors, respectively, in recognition of their D2-like properties. Given the unexpected heterogeneity of the dopaminergic receptor system, it is logical to ask if there are other dopamine receptor subtypes remaining be identified. This seems probable, as the characteristics of the cloned subtypes do not match all of the properties of some dopamine receptors which have been previously investigated. For instance, there is extensive evidence that "D1-like" dopamine receptors exist which are linked to the activation of phospholipase C, phosphatidylinositol turnover, and Ca2+ mobilization. Dopamine, as well as several "D1-selective" agonists, has been shown to stimulate phosphatidylinositol turnover in both brain slices and kidney membranes (Felder et al., 1989; Undie and Friedman, 1990; Vyas et al., 1992), and injection of striatal mRNA into Xenopus oocytes leads to dopamine-stimulated phosphatidylinositol turnover and Ca2+ mobilization (Mahan et al., 1990). These dopamine receptors might be analogous to the alpha 1-adrenergic receptors which stimulate phospholipase C activity and might define a third distinct subfamily of dopamine receptors. There is also evidence for additional members of the D2 subfamily of receptors. Using gene transfer methods, a receptor with D2-like pharmacology has been identified and expressed but not yet sequenced (Todd et al., 1989). Also, a D2-related receptor has been characterized in kidney inner medulla membranes (Huo et al., 1991). It thus appears that there may be more dopamine receptor subtypes yet to be discovered. PMID- 8463064 TI - Molecular aspects of photoreceptor adaptation in vertebrate retina. PMID- 8463066 TI - Cardiovascular disease: treatment and referral. PMID- 8463065 TI - The neurobiology and genetics of infantile autism. AB - Autism is a syndrome with multiple etiologies, as is made clear both by the evidence of neurobiological research and by the catalog of disorders that present with autistic behaviors. What remains unclear are the specific neuropathological mechanisms that produce autistic behaviors; for example, is there a common neuroanatomic pathology for all cases of autism, or can autistic behaviors emerge from different pathological sequences within the brain? Although it is premature to generalize, neuropathological studies appear to have identified common abnormalities in the cerebellum and limbic system of at least five autistic subjects. These subjects, with variable levels of mental retardation, demonstrated marked Purkinje cell loss in the cerebellar hemispheres, together with retained fetal neuronal circuitry in cerebellar nuclei and increased neuronal packing in specific regions of the limbic system, amygdala, and hippocampus. The architecture of the cerebral cortex was not affected. Although our knowledge of brain functioning is incomplete, alterations of the kind noted in the cerebellum and limbic system could reasonably produce autistic behaviors. For more detail, readers are directed to a review of cerebellar contributions to higher functions by Schmahmann (1991). Neuroimaging studies allow less resolution of brain structure than do neuroanatomic studies, and the reported findings from neuroimaging are somewhat contradictory. However, a number of investigators have reported structural abnormalities in ventricle size and cerebral hemispheric asymmetry using CT. MRI, which offers greater resolution, has uncovered some consistent findings, along with a variety of nonspecific abnormalities. Common abnormalities include reduced volume of cerebellar hemispheres and vermal lobules -findings not inconsistent with the above-mentioned neuropathological defects. It is also interesting to note that individuals with fragile X syndrome have similar cerebellar findings. PET and NMR studies of autism are at a preliminary stage, but these methodologies allow insight into the functioning of the brain, rather than simply brain anatomy. Recent PET studies indicating decreased association between paired regions of the brains of autistic subjects are of interest, particularly if they can be confirmed and refined by additional studies. Neurophysiological studies also offer insight into brain function, but are subject to numerous methodological criticisms. Nevertheless, recent reports of diminished P300 waves and absent NC components in autistic subjects seem to indicate fundamental defects in attention and secondary processing, which could help explain the self-stimulatory behaviors often seen in autism. The disturbances in brain development associated with autism can be produced in a number of ways, and at different times during development of the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463067 TI - Intussusception presenting as encephalopathy. PMID- 8463068 TI - Is your management team operating effectively? PMID- 8463069 TI - Quanta of ambiguity. PMID- 8463071 TI - Want to just be a doctor? Try locum tenens. PMID- 8463072 TI - Heart disease and Iowa's high school athletes. PMID- 8463074 TI - Dying safely. PMID- 8463073 TI - Medical treatment rights of older persons and persons with disabilities: 1991-92 developments. AB - This article covers developments occurring from the beginning of October 1991 to the end of September 1992. During this period, the federal government considered the issues of health care rationing, the medical rights of residents in long-term care facilities, and advance directives. The federal courts decided cases involving section 504 and its application to medical treatment decisions, the due process rights of persons needing medical care, and the liberty to accept or refuse medical treatment. The states continued to consider legislation on advance directives and surrogate decision making. Numerous state courts heard cases involving such issues as the removal of life-sustaining treatment from never competent persons, the definitions of living human being and personhood with respect to individuals with substantial disabilities, and the legalization of lethal injections and assisted suicide. PMID- 8463075 TI - Assisted suicide and the case of Dr. Quill and Diane. PMID- 8463076 TI - What about legalized assisted suicide? PMID- 8463077 TI - Euthanasia: a concept whose time has come? PMID- 8463078 TI - In re guardianship of Doe. PMID- 8463079 TI - In re L.W. PMID- 8463080 TI - Christian Medical & Dental Society ethical statement: suicide. PMID- 8463081 TI - Christian Medical & Dental Society ethical statement: physician-assisted suicide. PMID- 8463082 TI - The Southern Baptist convention. Resolution on euthanasia and assisted suicide. PMID- 8463083 TI - In loco parentis. Minimal risk as an ethical threshold for research upon children. PMID- 8463084 TI - In the U.K., children can't just say no. PMID- 8463085 TI - In Hungary, children help decide. PMID- 8463086 TI - Getting the bad news about your artificial heart valve. PMID- 8463088 TI - Keeping moral space open. New images of ethics consulting. PMID- 8463087 TI - How best shall we serve? Case study. PMID- 8463090 TI - Save the life of the child. PMID- 8463089 TI - Meeting at Maastricht. PMID- 8463091 TI - What kind of leave? PMID- 8463092 TI - What do you say to a child with AIDS? PMID- 8463093 TI - [Staphylococcus aureus and atopic eczema]. AB - The bacterial skin flora of patients with atopic eczema is different from that in healthy normal persons. In addition, such patients more often suffer from microbial infections. Differences in sebum and sweat secretion and increased bacterial adhesion to epithelial cells in atopic eczema may predispose to enhanced amounts of Staphylococcus aureus, for example, on the skin. Defective host-defence mechanisms with dysfunction of cellular and humoral immune reactions have been suggested. On the other hand, bacterial antigens may induce allergic reactions, e.g. increased IgE synthesis and enhanced expression of the low affinity receptor for IgE (CD23, Fc epsilon RII), and the release of inflammatory mediators such as leukotrienes and histamine. The production of bacterial toxins might be important for the pathophysiology of atopic eczema. This paper summarizes the present data and tries to integrate them into a model for the induction of atopic eczema. PMID- 8463094 TI - [Dexamethasone-cyclophosphamide pulse therapy in bullous autoimmune dermatoses]. AB - The problem in the treatment of bullous autoimmune dermatoses with long-term corticosteroids is that the high doses cause side-effects. An alternative form of therapy with high-dose dexamethasone-cyclophosphamide pulses was used to treat 20 patients between 33 and 86 years: 7 patients had bullous pemphigoid, 6 pemphigus vulgaris, 5 pemphigus foliaceus, and 2 cicatricial pemphigoid. On each of days 1 3 100 mg dexamethasone was administered i.v. and on day 1, 500 mg cyclophosphamide i.v. In the therapy interval between the pulses 50 mg cyclophosphamide per day. Initially the pulses were repeated every 2 weeks and later at 10-week intervals. After 6 months of this regimen 13 patients were symptom-free, 4 had improved, and 3 showed no change. The efficacy of treatment was equal in newly diagnosed and previously treated cases. (Side-effects were leucopenia (n = 3), myalgia and arthralgia (n = 2), taste disturbance (n = 2), diffuse hair loss (n = 2), thrombophlebitis (n = 1), herpes zoster (n = 1) and a delayed-type hypersensitivity reaction to mesna. Owing to the rather short follow up, no conclusions on long-term side-effects of this therapy are possible. However, dexamethasone-cyclophosphamide pulse therapy appears so far to be a good alternative to the standard continuous corticosteroid treatment. PMID- 8463095 TI - [Imre modified bilobed flap rotation graft for plastic surgery management of skin tumors in the area of the nose and eyes]. AB - The modification and development of the rotation-flap graft described by Imre in 1924 gave rise to the bilobed flap rotation graft, which is now a standard operative method of defect coverage and corrective plastic surgery, especially for the facial region. The advantages of this operative technique are presented with reference to case reports. They result from its ability to neutralize the tractive and expansion forces that arise within the tissue and to guarantee adequate blood supply to and innervation of the rotation flap by shifting the axis of rotation to a site far distant from the operating area. PMID- 8463096 TI - [Incontinentia pigmenti in a male patient]. AB - Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare genetic disorder usually affecting females. Familial cases show an X-linked dominant inheritance with male lethality. The typical skin manifestations occur in several stages and can be associated with various extracutaneous anomalies. We report on a 10-month old male patient with incontinentia pigmenti (IP) and a normal male karyotype. Besides the typical cutaneous lesions no other signs have been found so far. IP in male patients can be explained by the presence of Klinefelter syndrome, by the half-chromatid mutation model, or by an early somatic mutation. On the basis of this case report we discuss the clinical findings in and the genetics of IP. PMID- 8463097 TI - [Camptodactyly. The syndrome of flexion contracture of the fingers]. AB - We report on three cases of a nonpainful flexion contracture of the proximal interphalangeal joint of the little finger. The word camptodactyly means bent finger, and the condition can occur either as an inherited or as a sporadic disorder. Simple camptodactyly should be borne in mind in the differential diagnosis of Dupuytren's contractures, other nontraumatic contractures of the fingers, and sclerodermia. PMID- 8463098 TI - [Cutaneous condylomata acuminata of an unusual site and extent. Successful CO2 laser therapy]. AB - We report on a 33-year-old patient with unusually extensive and predominantly cutaneous condylomata acuminata spreading from the penis over the mons pubis to the entire lower abdominal wall but almost completely sparing the genital mucous membranes. Single lesions were found on the left arm and on the buttocks. Southern blot hybridization detected HPV-6a DNA sequences within the fibroepithelial tumours. Carbon dioxide laser treatment resulted is cosmetically acceptable healing without recurrence. PMID- 8463099 TI - [Malignant blue nevus]. AB - A 35-year-old male patient suffering from a malignant blue naevus is presented. An uncommon melanocytic naevus and malignant melanoma were considered in the differential diagnosis. The final diagnosis was established by histological examination. Immunohistochemical studies showed a strongly positive reaction of the tumour cells for vimentin and S-100 protein. In addition, tumour cells reacted with the antibody HMB-45. PMID- 8463100 TI - [Pemphigus foliaceus caused by penicillamine]. AB - We report the case of an 80-year-old woman who developed pemphigus foliaceus while taking penicillamine for rheumatoid arthritis. On the basis of this new case, we discuss fresh insights into the pathogenesis of drug-induced pemphigus. In addition, having reviewed the literature, we give a list of drugs that have been reported to induce this disease. PMID- 8463101 TI - [Metastasizing eccrine porocarcinoma]. AB - We report on an 84-year-old female patient who presented with abundant firm skin nodules and massive lymphoedema restricted to the left leg. Metastasizing eccrine porocarcinoma was diagnosed by the unusual circumscribed pattern of the cutaneous metastases and the histological detection of intraepidermal and intradermal PAS positive tumour cells. This diagnosis was established by the histopathological reexamination of a small skin tumour on the left ankle, which had been misinterpreted as actinic keratosis 5 years before. The initiated local radiation therapy with fast neurons and cobalt-60 resulted in partial regression of the cutaneous metastases and lymphoedema, but was not able to hamper the fatal outcome directly resulting from tumour cachexia. PMID- 8463103 TI - [Morphology and follow-up of seborrheic eczema] ]. PMID- 8463102 TI - [Tapered treatment with corticosteroids]. PMID- 8463104 TI - [Historical development of skin surface microscopy]. AB - Within the last decade, skin surface microscopy has been rediscovered as an useful technique for preoperative diagnosis of pigmented skin lesions. This method was originally developed early this century as one component of "functional diagnosis" in constitutional pathology. PMID- 8463105 TI - [Decreased work capacity in dermatologic expert assessment. Comment on the contribution by T. Bergner et al]. PMID- 8463106 TI - [Antimycotic agents. I]. PMID- 8463107 TI - Factors affecting conversion rates to Medicaid among new admissions to nursing homes. AB - OBJECTIVE: This study examines conversion to Medicaid as a payment source among a cohort of newly admitted nursing home residents. DATA SOURCE: The longitudinal data used came from regular assessments of residents in the National Health Corporation's 43 for-profit nursing homes in Missouri, Kentucky, South Carolina, and Tennessee. This information system tracked all residents who were discharged, providing a comprehensive record that may have spanned multiple admissions. STUDY DESIGN: Using survival analysis methods, Cox regression, and survival trees, we contrasted the effect of state, initial payment source, education, age, and functional status on the rate of spend-down to Medicaid. DATA EXTRACTION METHODS: New-admission cohorts were created by linking an admission record for a newly admitted resident with all subsequent assessments and follow-up records to ascertain the precise dates of any payment source changes and other discharge transitions. PRINCIPAL FINDINGS: For the 1,849 individuals who were admitted as self-payers and who were still in the nursing home at the end of one year, there is a 19 percent probability of converting to Medicaid. All analytic methods revealed that education, age, and state of residence were predictive of spend down among residents who were admitted as self-payers. CONCLUSIONS: Our results confirm the effect of education as an SES indicator and state as a proxy for Medicaid policy on spend-down. Future research should model the effects and duration of intervening hospitalizations and other transitions on Medicaid spend down among new admissions. PMID- 8463108 TI - ASIM: a system for monitoring and evaluating the long-term care of the elderly and disabled. AB - OBJECTIVE: A system for monitoring and evaluating the long-term care of the elderly and disabled is presented, and its problems of completeness, reliability, and validity are discussed. DATA SOURCES/STUDY SETTING: Half-yearly (before 1987) and yearly (after 1987) surveys were taken from 1984 to 1990 of all persons living in the city of Solna, Sweden, who at May 1 and November 1, or November 1, were receiving long-term care services from the municipality or county council, or both. STUDY DESIGN: Completeness of observations was studied by linking survey and admission/discharge observations and checking for breaks in the chain of care. Reliability was estimated by comparing involuntary double registrations. Validity of the chosen measures of need was tested by comparing them with the actual provision of care services. DATA COLLECTION: Registrations concerning actually provided services, assessed need, social environment, and disability were collected on a regular basis by the staff responsible for the care services. PRINCIPAL FINDINGS: Completeness was estimated to be more than 99 percent after a special procedure was carried out for filling in gaps in the "care chain." Reliability testing of the disability measures showed between .69 and .76 Kappa coefficient of agreement. Disability variables were shown to explain 56 percent of variance in the need measure "appropriate level of care." CONCLUSIONS: Tests of completeness, reliability, and validity showed satisfactory results with regard to the purpose of the monitoring system and the limitations inherent in a system intended for routine application. PMID- 8463109 TI - Effect of prospective reimbursement on nursing home costs. AB - OBJECTIVE: This study evaluates the effect of Maine's Medicaid nursing home prospective payment system on nursing home costs and access to care for public patients. DATA SOURCES/STUDY SETTING: The implementation of a facility-specific prospective payment system for nursing homes provided the opportunity for longitudinal study of the effect of that system. Data sources included audited Medicaid nursing home cost reports, quality-of-care data from state facility survey and licensure files, and facility case-mix information from random, stratified samples of homes and residents. Data were obtained for six years (1979 1985) covering the three-year period before and after implementation of the prospective payment system. STUDY DESIGN: This study used a pre-post, longitudinal analytical design in which interrupted, time-series regression models were estimated to test the effects of prospective payment and other factors, e.g., facility characteristics, nursing home market factors, facility case mix, and quality of care, on nursing home costs. PRINCIPAL FINDINGS: Prospective payment contributed to an estimated $3.03 decrease in total variable costs in the third year from what would have been expected under the previous retrospective cost-based payment system. Responsiveness to payment system efficiency incentives declined over the study period, however, indicating a growing problem in achieving further cost reductions. Some evidence suggested that cost reductions might have reduced access for public patients. CONCLUSIONS: Study findings are consistent with the results of other studies that have demonstrated the effectiveness of prospective payment systems in restraining nursing home costs. Potential policy trade-offs among cost containment, access, and quality assurance deserve further consideration, particularly by researchers and policymakers designing the new generation of case mix-based and other nursing home payment systems. PMID- 8463110 TI - Ecological analysis of the first generation of community clinical oncology programs. AB - OBJECTIVE: An ecological framework is proposed for assessing factors important to consider in allocating funds to promote sound performance of interorganizational programs. DATA SOURCE/STUDY SETTING: This framework is used to examine the first generation of Community Clinical Oncology Programs (CCOPs) funded by the National Cancer Institute (NCI) from 1983-1986 to coordinate clinical research activity at the local level. The research reported is based on secondary data collected for the Community Cancer Care Evaluation at the Fred Hutchinson Cancer Center. STUDY DESIGN: A repeated measures design was used to analyze differences in the level and patterns of CCOP productivity, a measure of the number of patients enrolled on NCI-approved Phase III trials. The predictive dimensions include (1) measures of environmental inputs (population density, organizational dominance, professional support, NCI funding); (2) measures of organizational inputs (number of hospitals, number of staff, number of physicians, NCI experience, clinical research experience); and (3) structural measures (functional specialization, administrative concentration). Predicted relationships were assessed using general linear models procedures. DATA COLLECTION/EXTRACTION METHODS: Data obtained from NCI files were supplemented by interviews with NCI personnel and published statistics. PRINCIPAL FINDINGS: Funding level, clinical research experience, and number of staff are the most important predictors of patient enrollment. Clinical research experience has a positive relationship with patient enrollment and a negative association with changes in enrollment. The reversal is explained by the influence of the CCOPs that had the greatest amount of clinical research experience at the beginning of the program. CONCLUSIONS: The ecological approach provides a useful framework for understanding factors that should be considered in funding interorganizational programs and promoting their development. Most importantly, results suggest that a somewhat different approach is needed to initiate programs rather than to expand existing programs. PMID- 8463112 TI - [Is a transplantation law necessary?]. PMID- 8463111 TI - A cost-effectiveness analysis of hepatitis B vaccine in predialysis patients. AB - OBJECTIVE: Our objective was to assess the cost effectiveness of hepatitis B vaccine in predialysis patients. DATA SOURCES: Costs were calculated from estimated rates of health services use and unit costs of resource use. Efficacy data were based on probability estimates from the medical literature and included vaccination response rates, anticipated hepatitis B virus (HBV) infection rates, and outcomes from HBV. STUDY DESIGN: Costs and effectiveness of HBV vaccination was modeled with a decision tree constructed to analyze three vaccination strategies for patients with renal insufficiency: vaccine given prior to dialysis, vaccine given at time of dialysis, and no vaccine. Sensitivity analyses were performed to assess the effect of varying important clinical and cost variables. DATA COLLECTION/EXTRACTION METHODS: All analyses were based on efficacy and cost estimates derived from the medical literature. Analyses were conducted with the aid of SMLTREE software. PRINCIPAL FINDINGS: The number of patients requiring vaccination per case of HBV prevented was higher for dialysis patients (625 vaccinees/case prevented) than for predialysis patients (434 vaccinees/case prevented). The cost-effectiveness ratios were $25,313/case of HBV prevented for vaccination at the time of dialysis and $31,111 for the predialysis vaccine. When a higher HBV infection rate (based on clinical trial data) was substituted in the analysis, the cost effectiveness of a predialysis vaccination strategy improved to $856 per case prevented. Results were sensitive to the cost of the vaccine and the incidence of HBV infection in dialysis patients. For the predialysis strategy to become cost saving, the price of the vaccine would have to decrease from $114 to $1.50, or the incidence of infection would have to increase from 0.6 percent to 38 percent, holding all other variables constant. CONCLUSIONS: Additional HBV infection can be prevented by immunizing predialysis patients, but the cost is high. Decisions concerning vaccination policy should be influenced by local prevalence of HBV infection. PMID- 8463113 TI - ["Ultrasound hearing aid" for deaf patients? Comments on human ultrasound hearing]. PMID- 8463114 TI - [Microvascular tissue transfer in the area of the head-neck. Status of the technique and outlook]. PMID- 8463115 TI - [List of damage to the mucous membranes of the upper aerodigestive tract caused by chemically irritating, toxic and allergic environmental substances]. PMID- 8463116 TI - [Social responsibility for organ donation. Legal aspects of modern transplantation surgery]. AB - In the recent past there has been considerable discussion about the legal and legislative aspects of transplantation surgery. The present legal codes with German reunification now require a uniform law for the country as a whole. In addition to the different legal models already presented, any "expanded" agreement must not only respect the right of self-determination but also the responsibility of the individual for his societal obligations. The German legislator is now required to enact a uniform law which is reasonable and also considers the necessities of modern transplantation medicine in order to have the best concordance of the constitutional laws involved. PMID- 8463117 TI - [Perspectives of molecular genetics of hearing disorders]. AB - In the last few years research efforts have succeeded in detectury the genetic background of several hereditary hearing disorders by molecular biological methods. The genetic code was been decoded for Neurofibromatosis types 1 and 2, as well as for such X-linked diseases as Alport's syndrome or Norrie's disease. Besides the classic genetic tools as chromosomal analysis, molecular biological techniques and methods have become important clinically for the ENT-specialist. In the present review we show the principles and applications of DNA-and RNA analysis with hybridization techniques in Southern- and Northern-blot techniques, as well as in-situ hybridization and polymerase chain reaction (PCR). These molecular biological techniques will help improve the detection and analysis of hereditary inner ear disorders, but also be able to study in greater detail tumor carcinogenesis and mutagenesis. The various techniques are explained and the applications are demonstrated. PMID- 8463118 TI - [Otosclerosis in the elderly. The effect of stapes-plasty on hearing ability and hearing aid management]. AB - We examined 105 patients who underwent partial stapedectomies at the age of 65 years or older as treatment for combined hearing losses due to otosclerosis. Among other things investigated was the influence of the operation on the hearing of both the operated and unoperated ears, as well as on tinnitus existing preoperatively and the use of a hearing aid. Findings showed that tinnitus decreased or vanished in 75% of the cases. Sixty-one percent of the patients needed a hearing aid continuously preoperatively, with 48% not needing it post operatively and 13% using it only occasionally. The degree of sensorineural hearing loss had by the other patients was so severe that the use of a hearing aid was also necessary post-operatively. However, in some of these cases, a successful use of a hearing aid became possible for the first time due to the surgical improvement in hearing. PMID- 8463119 TI - [The epidemiology of parotid tumors. A case control study]. AB - From 1989 to 1991 a case-control study was conducted at the ENT Department of the University of Heidelberg. One hundred and one patients with parotid tumors (84 benign and 17 malignant) were compared with 404 control patients in a matched pair study design. Using a questionnaire containing 21 sides, all interviews were conducted by the same interviewer. The questionnaire contained such aspects as "professional surroundings and exposure to environmental dusts", "consumption of tobacco and alcohol", "living area", "nutrition", "hobbies" and "social life". Questions about personal and familial diseases, consumption of medicine and exposure to irradiation were also asked. Differences in exposure to occupational dusts were seen. The highest relative risk (RR) for developing a parotid tumor was seen with weekly exposure to nickel during a period of more than 10 years (RR = 6.0; confidence interval, 1.4-25.5). Similar risk was found with exposure to chromium, asbestos and cement dusts (RR chromium = 3.4; confidence interval, 0.9 14.5; RR asbestos + cement = cement 3.0, confidence interval 1.0-8.9). Higher relative risks were also detected in patients exposed to diagnostic dental x rays. PMID- 8463120 TI - [Personal experience with Ionocem in head- and neck surgery]. AB - Ionomeric bone bond cement (Ionocem) is a new alloplastic bone replacement material, which was used by us for functional and aesthetic purposes in surgery of the head and neck. We have used the cement 44 times (in 43 patients) for repair of skull and mid-face trauma, reconstruction of defects after tumor removal and for aesthetic augmentation. Ionocem was distinguished by its ready shaping on existing bony structures, its adaptation of bone fragments and bone implants without gaps and its help in avoiding ancillary procedures requiring autogenous grafts. Complications occurred in 22 patients, with most involving swelling, seromas, granulation, fistulas and sequestration which occurred after unsuitable indications or application. PMID- 8463121 TI - [Endoscopic paranasal sinus surgery. The most important anatomic variations of the main paranasal sinus and accessory paranasal sinus]. AB - Anatomic variations of the nasal cavity and paranasal sinuses are described in order of their appearance in endoscopy. Variations of the pyriform aperture are followed by variations of the agger nasi, inferior and middle conchas, inferior and middle nasal meati, and variations of the bulla ethmoidea, uncinate process and fontanelles. Variations of the maxillary sinus are described from their anterior and lateral views. Partial and total septation of the maxillary sinus, variations of its dimensions and its relation to dental roots are stressed. The dimensions of the frontal sinus, frontal bulla or bullae are noted. The variation of the sphenoid sinus and its dimensions and relationships to the structures of the cavernous sinus and the endocranium are described. Pneumatization of the anterior clinoid process and the region around the optic canal by the frontal sinus, ethmoid labyrinth or sphenoid sinus is discussed. Knowledge of these different variations will help the rhinologic surgeon in his orientation during endoscopic surgical interventions. PMID- 8463122 TI - Unfolded HLA class I alpha chains and their use in an assay of HLA class-I peptide binding. AB - Unfolded HLA class I alpha chains were isolated from B-cell lysates by alkaline denaturation and subsequent gel filtration and used for the detection of HLA class-I-peptide binding. Binding to specific peptides in the presence of excess beta 2-microglobulin induced the unfolded alpha chains to refold and acquire a conformation that is specific to folded alpha chains. This conformational change was measured by a specific RIA that involves inhibition of the binding of 125I labeled HLA-A2 alpha/beta dimers and rabbit anti-HLA-B7 serum absorbed with beta 2-microglobulin. This assay procedure does not require labeling of either test peptides or test class I proteins and does not seem to have specificity degeneracy. It is applicable to the detection of peptide binding by all HLA class I allelic proteins. Evaluation of the assay conditions and HLA allelic specificity of the peptide binding defined by the use of synthetic peptides are described here, including the technical details, specificity, and reproducibility. PMID- 8463123 TI - Heterogeneity of type-II interleukin-1 receptors. Heterogeneity of B-cell interleukin-1 binding created by dimerization of type-II interleukin-1 receptors. AB - The binding of IL-1 alpha and IL-1 beta to two human lymphoblastoid B-cell lines, Raji and RPMI 1788, was compared with binding to the murine T-cell line, EL4. Dramatic differences in IL-1 binding were observed. Both human B-cell lines bound much less IL-1 alpha than IL-1 beta, expressed 5-10 times more receptors per cell for IL-1 beta than did the EL4 cell line, and demonstrated a large difference in the ability of IL-1 alpha to compete with IL-1 beta for binding. The B-cell lines demonstrated a low number of high-affinity IL-1 alpha receptors and a large number of IL-1 alpha receptors with a much lower affinity. Inhibition studies demonstrated that only IL-1 beta could compete for the binding of radiolabeled IL 1 beta to the B-cell IL-1R. Furthermore, SDS-PAGE analyses of lysates of the B cell lines that had been affinity cross-linked with 125I-IL-1 alpha revealed two bands corresponding to IL-1R structures of 60 and 110 kD. These results coupled with a nonequilibrium binding study suggested a dimerization of a common type-II IL-1R polypeptide, the dimer being responsible for the high-affinity IL-1 alpha binding site of the B-cell lines. PMID- 8463124 TI - Identification of alloantisera reacting with HLA-C blank (Cx52) using a mouse L cell transfected with the HLA-Cw*1201 allele. AB - The HLA-C locus frequently has a serologically undefined "blank" (CwBL) specificity. A cDNA clone derived from the HLA-C gene with a blank specificity (Cx52) strongly associated with the most common haplotype in a Japanese population, A24-CwBL-B52-DR2-DQ6-DP9, has been recently cloned and sequenced in our laboratory and officially designated Cw*1201 as an allelic name, indicating that the inability to define the HLA-C antigen serologically in this haplotype is not due to an HLA-C antigen gene deletion or mutation, but to the absence of typing sera. In this paper, a mouse L-cell transfectant expressing this Cw*1201 gene product was constructed and employed for screening of alloantisera recognizing the HLA-C antigen with the Cw*1201 specificity. Two alloantisera against Cw*1201 were thus identified and characterized using HLA homozygous B cell lines and local panel PBL cells, indicating that a transfectant expressing a single HLA provides an efficient screening system for collection of HLA-typing sera, especially reacting with serologically unclassifiable "blank" antigens. PMID- 8463125 TI - Defective signal transduction via T-cell receptor-CD3 structure in T cells from rheumatoid arthritis patients. AB - T cells from patients with active RA are known to produce low levels of IL-2 and proliferate poorly in response to various mitogenic stimuli. The present work shows that cross-linking of CD3 antigen on patients' T-cell surface induces two- to threefold lower Ca2+ response than in T cells from age-matched controls. Immunofluorescence studies indicate that the attenuated signal may be due to the suppressed expression of CD3 and/or CD45 molecules on patients' T cells. In the majority of the patients, the level of CD45 expression is reduced by 60%-70% as compared with that in the control T cells. Therefore, the poor mitogenic response of patient cells is apparently due to a defect in early stages of signal transduction through the T-cell receptor (TCR-CD3). PMID- 8463126 TI - Cytochrome P-450: the Japanese connection. PMID- 8463127 TI - Induction of BCR-ABL fusion genes by in vitro X-irradiation. AB - The Philadelphia chromosome consists of a reciprocal translocation between the ABL oncogene at chromosome 9q34 and the BCR gene at chromosome 22q11, resulting in the expression of chimeric BCR-ABL mRNAs specific to chronic myelogenous leukemia (CML). Presence of the fusion gene can be detected with high specificity and sensitivity by means of reverse transcription and polymerase chain reaction. Using this assay, it was possible to detect BCR-ABL fusion genes induced among HL60 cells after 100 Gy of X-irradiation in vitro. In total, five fusion gene transcripts were obtained among 10(8) cells examined. These fusion genes contained not only CML-specific BCR-ABL rearrangements, but also other forms of BCR-ABL fusions. These latter genes had junctions of BCR exon 4/ABL exon 2 intervened by a segment of DNA of unknown origin, BCR exon 5/ABL exon 2, and BCR exon 4/ABL exon 2. The results appear to be direct evidence for the induction of the BCR-ABL fusion gene by X-irradiation. In terms of leukemogenesis, it appears that only those cells bearing certain CML-related BCR-ABL fusion genes are positively selected by virtue of a growth advantage in vivo. PMID- 8463128 TI - Helicobacter pylori may be transmitted through gastrofiberscope even after manual Hyamine washing. AB - Endoscopy is an effective diagnostic technique for gastric cancer, which is believed to be associated with Helicobacter pylori. Manual Hyamine washing is a widely used fiberscope cleaning method. Urease B gene of Helicobacter pylori was detected in 50% of the wash-out samples from the biopsy-suction channel of a fiberscope after manual Hyamine washing by nested polymerase chain reaction, and bacterial culture revealed viable Helicobacter pylori in 19%. However, Helicobacter pylori was not detected by either of the above methods in the biopsy suction channel of the fiberscope after mechanical washing. These findings indicate that manual Hyamine washing of fiberscopes is insufficient to prevent iatrogenic Helicobacter pylori transmission, and that mechanical washing after manual Hyamine washing is essential. PMID- 8463129 TI - Inhibitory effects of inhibitors of arachidonic acid metabolism on the evolution of rat liver preneoplastic foci into nodules and hepatocellular carcinomas with or without phenobarbital exposure. AB - Effects of inhibitors of arachidonic acid (AA) metabolism on the evolution of preneoplastic foci into nodules and of nodules into hepatocellular carcinomas were examined in F344 male rat livers with or without phenobarbital (PB) exposure. p-Bromophenacyl bromide (BPB), acetylsalicylic acid (ASA), and quercetin (QU) were used as inhibitors of phospholipase A2, cyclooxygenase and lipoxygenase, respectively. Preneoplastic liver foci were induced by initiation with N-nitrosodiethylamine (200 mg/kg, i.p.) followed by selection using the procedure of Cayama et al. For the nodule experiment, starting 1 week after completion of the selection procedure, animals bearing foci were given diets containing 0.05% PB plus 0.75, 1, or 1.5% of one of the inhibitors, 0.05% PB alone, or 0.75, 1 or 1.5% of inhibitor alone, or basal diet for 9 weeks. For the carcinoma experiment, 3 weeks after completion of the selection procedure, animals bearing nodules were given the same diets mentioned above for 29 weeks. BPB, ASA and QU either with or without PB accelerated the remodeling of preneoplastic foci, significantly decreasing the numbers of persistent nodules and hyperplastic nodules. ASA either with or without PB significantly decreased the number of hepatocellular carcinomas per rat. BPB and QU, however, significantly decreased the numbers of hepatocellular carcinomas with but not without PB. The results suggested an involvement of AA metabolism in the process of evolution of preneoplastic foci into nodules and hepatocellular carcinomas in rat liver with or without PB exposure. PMID- 8463130 TI - Time-dependent modulation of liver lesion development in Opisthorchis-infected Syrian hamster by an antihelminthic drug, praziquantel. AB - In the North-east of Thailand, repeated antihelminthic therapy has been introduced for control of the opisthorchiasis known to be a major risk factor for cholangiocellular carcinomas. What influence this may have on tumorigenesis, however, remains unclear. The effects of administration of praziquantel, an antihelminthic drug, at different time points subsequent to infection with Opisthorchis viverrini (OV) on 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) initiated lesion development in the liver of female Syrian hamsters were therefore investigated. Praziquantel (250 mg/kg body weight, i.p.) was given 4, 12 or 20 weeks after infection of DHPN-treated animals (two 1000 mg/kg i.p. injections at weeks 0 and 2) with 60 OV metacercariae (at week 4). Survivors at week 38 were killed and examined. It was found that whereas praziquantel administration at the earlier two time points was effective at reducing hepatocellular nodule development, the results for cholangiocellular lesions were less pronounced, significant reduction only being evident in hamsters treated 4 weeks after parasite infestation. The findings thus indicate that enhancement of DHPN-initiated bile duct carcinogenesis by opisthorchiasis is both rapid and to a large degree irreversible. Hepatocellular lesion development in this model, on the other hand, appears to correlate more closely with the duration of parasite associated proliferative stimulus. PMID- 8463131 TI - Influence of aging on multi-organ carcinogenesis in rats induced by N-methyl-N nitrosourea. AB - The effects of aging on the multi-organ carcinogenesis induced in rats by N methyl-N-nitrosourea (MNU), a direct carcinogen which does not need metabolic activation to exert carcinogenicity, were examined in male F344 rats. In the first experiment, rats at 6, 52, and 98 weeks of age were treated with MNU (20 mg/kg body weight, i.p.) twice weekly for 6 weeks and then maintained without any further treatment for 24 weeks in the case of young and middle-aged rats and for 18 weeks in the case of the old rats. In young rats, malignant lymphomas, particularly thymic types, were observed at significantly high incidence. A striking result in the middle-aged rats was the significantly higher incidence of adenocarcinomas in the small intestine than in young or old animals. The induction of proliferative and neoplastic lesions of the large intestine also tended to be increased in middle-aged rats. In addition, epithelial hyperplasia of the tongue, but not the forestomach, occurred at the highest incidence in the middle-aged group. There were no differences in the induction of epithelial lesions in the urinary bladder among the groups. In a second experiment, investigation of DNA synthesis in the tongue, small and large intestines, urinary bladder and lymph nodes did reveal significant increases or tendency for increase in the MNU-treated groups, but without differences with age. In contrast, the thymus of young rats showed significantly increased incorporation of BrdU label after administration of MNU, whereas it was markedly reduced in middle-aged rats. In a third experiment, O6-methyldeoxyguanine (O6-medG) DNA adduct formation was immunohistochemically detected in various organs including the thymus, forestomach, and small intestine without any differences with age. Thus, the results demonstrated that while the target organs of MNU are modified by the age of the animals, levels of DNA synthesis and O6-medG DNA adduct formation in most cases can not explain the observed differences in carcinogenic susceptibility. PMID- 8463132 TI - Persistently human immunodeficiency virus type 1-infected T cell clone expressing only doubly spliced mRNA exhibits reduced cell surface CD4 expression. AB - Several cell clones possessing the human immunodeficiency virus type 1 (HIV-1) genome, consisting of an almost full-length DNA sequence, were isolated by limiting dilution of the clonal cell line M10 derived from MT-4 that survived infection with HIV-1 vpr mutant (M10/vpr-). One of the isolated clones (termed Vpr-1) expressed only doubly spliced mRNA, but not unspliced or singly spliced mRNA. Western blots of Vpr-1 revealed the presence of the nef translation product, although no expression of major structural genes such as gag, pol, and env was detected by indirect immunofluorescence and assay of reverse transcriptase activity. These HIV-1 phenotypes differed greatly from those of the original M10/vpr-, most of which expressed major structural HIV-1 proteins. Despite undetectable levels of env expression in Vpr-1, CD4 antigens were greatly down-modulated on the surface without alteration of steady-state levels of CD4 mRNA expression, similar to M10/vpr-. These HIV-1 phenotypes in Vpr-1 did not change after the treatment of the cells with both phorbol 12-myristate 13-acetate and phytohemagglutinin. Therefore, the abnormal HIV-1 life cycle in Vpr-1 seems to be due to some viral factor(s), as well as cellular factors. Thus, Vpr-1 could be a useful model for understanding one HIV-1 latent form. PMID- 8463133 TI - Infrequent ras mutation in human stomach cancers. AB - Mutations of ras oncogenes in 37 human stomach cancers and 13 adenomas were investigated with regard to the histological phenotypes using polymerase chain reaction (PCR), allele-specific oligonucleotide hybridization and/or direct sequencing of the PCR products. The ras mutation was found only in one case (2.7%), the histology of which was poorly differentiated adenocarcinoma. We found no mutation in stomach adenomas. The mutation consisted of a guanine-to-adenine transition in the first base of codon 13 of c-Ki-ras which replaced wild-type glycine with serine, indicating that a putative glycine-to-aspartic acid change is not necessarily the critical event for c-Ki-ras gene activation in codon 13. These results further confirm the infrequency of ras mutation in stomach tumors and also suggest that ras mutations are not specific to the differentiated type of stomach cancer. PMID- 8463134 TI - Quantitative comparison of initiation and mutation phenotypes in hepatocytes of the analbuminemic rat. AB - The potential relationship between mutagenesis and carcinogenesis has been examined in the Nagase analbuminemic rat treated with a single dose of benzo[a]pyrene, an incomplete liver carcinogen. The apparent mutation rate at the albumin locus was calculated by determining the number of hepatocytes expressing a cross-reactive product of albumin in analbuminemic rats treated with benzo[a]pyrene. The rate of initiation, the first stage in carcinogenesis, was determined by assessing the number of hepatocytes expressing the placental isozyme of glutathione S-transferase (PGST) after administration of benzo[a]pyrene. Since the expression of PGST may represent hepatocellular changes independent of initiation, promotion with phenobarbital was employed to clonally expand those putatively initiated hepatocytes expressing PGST. With immunohistochemical measures to assess changes in albumin expression, a threefold increase in the number of hepatocytes expressing albumin was detected after administration of benzo[a]pyrene in Nagase analbuminemic rats. A more than five fold increase in altered hepatic foci (AHF) exhibiting increased PGST expression was observed in animals given benzo[a]pyrene treatment followed by phenobarbital, compared with those given benzo[a]pyrene alone. The number of albumin-expressing single hepatocytes detected was of the same order of magnitude as the number of individual hepatocytes and AHF expressing PGST, suggesting that similar events may be involved in their formation. Since 3 x 10(6) single hepatocytes expressing albumin were found in the analbuminemic rat liver after a single administration of benzo[a]pyrene, while less than 2 x 10(4) AHF expressing PGST were observed, formation of individual hepatocytes expressing albumin was a far more frequent event than clonal expansion of initiated hepatocytes in the Nagase analbuminemic rat. However, the number of loci of PGST expression including AHF and single hepatocytes is comparable to that of single hepatocytes expressing albumin. PMID- 8463135 TI - Intracellular metabolism and cytotoxicity of transferrin-neocarzinostatin conjugates of differing molar ratios. AB - Transferrin-neocarzinostatin (NCS) conjugates with differing molar ratios of drug to protein were synthesized and their intracellular metabolism was investigated. The conjugate mixtures of transferrin-NCS were separated by DEAE-Sephacel column chromatography. The separated molecular species were examined with respect to binding affinity to transferrin receptor, cytotoxicity and intracellular metabolism using the human leukemia cell line, K562. Transferrin-NCS conjugate is capable of binding to transferrin receptors specifically and its reactivity became weaker as the ratio of bound NCS to transferrin was increased. Transferrin 6NCS did not bind measurably to the receptor. On the other hand, the cytotoxicity was augmented when the number of NCS molecules bound per molecule of transferrin was increased to 4NCS/transferrin, while transferrin-5NCS and transferrin-6NCS species exhibited low activity. Examination of the kinetics of metabolism by pulse chase study using 125I-labeled ligand indicated that unconjugated transferrin and transferrin-NCS conjugates were internalized in similar ways, although the degradation of internalized conjugate was more marked in the case of transferrin-4NCS than transferrin-1NCS. Thus, the molar ratio of transferrin-drug conjugate could be optimized with respect to both the binding activity to receptor and the intracellular metabolic pathway. PMID- 8463136 TI - Comparative studies on the metabolism of new fluorinated pyrimidine drugs in the liver by in vivo 19F magnetic resonance spectroscopic observation. AB - 1-Ethoxymethyl-5-fluorouracil (EM-FU) is a fluorinated pyrimidine derived from 5 FU, and 3-cyano-2,6-dihydroxypyridine (CNDP) is a chemical modulator which suppresses the catabolism of 5-FU by inhibiting dihydrouracil dehydrogenase in the liver. In this study, the metabolism of EM-FU and the suppression of 5-FU catabolism by CNDP were observed by in vivo 19F magnetic resonance spectroscopy in comparison with other similar drugs, because it is considered that the most effective mode of therapy using 5-FU is to suppress the catabolism of 5-FU in the liver and so to maintain for longer an effective blood level of 5-FU. The metabolism of EM-FU was very slow and the production of fluoro-beta-alanine was very low as compared to the case of tegafur. The catabolic suppression by CNDP was much stronger than that of uracil. Therefore co-administration of EM-FU and CNDP should suppress catabolism and maintain an effective blood level of 5-FU for a long period of time. PMID- 8463138 TI - Feeding sorbitol alone or in combination with monensin to finishing cattle. AB - Three trials were conducted with finishing steers to study the effect of feeding sorbitol alone or combined with monensin. For each trial 15 pens of eight steers were fed high-corn-silage diets. In the first two trials three pens of eight steers each were fed no additive, 35 g of sorbitol, 350 mg of monensin, or 30 g of sorbitol plus 350 mg of monensin per day. In Trial 1 three pens were fed 200 g of sorbitol per animal every 6 d, and in Trial 2 three pens were fed 60 g/d of sorbitol plus 350 mg/d of monensin. For the third trial, three pens were fed 0, 20, 40, or 80 g/d of sorbitol per animal and three pens were fed 40 g/d after 56 d; all the steers were fed 350 mg/d of monensin. In the first trial sorbitol had no effect on daily gain, and monensin increased (P < .05) daily gain. Intake of DM was lower (P < .05) for the steers fed sorbitol (35 g/d). Dry matter intake/gain was improved by feeding monensin (P < .05) or 35 g/d of sorbitol (P < .07). The improvement amounted to 18% when the additives were used in combination. In the second trial daily gains were similar for the cattle fed all diets. Dry matter intake was lower (P < .05) for steers fed monensin or 60 g/d of sorbitol and tended to be lower (P < .12) for the cattle fed 35 g/d of sorbitol. Dry matter intake/gain tended to be lower for cattle fed monensin and sorbitol, especially when fed in combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463139 TI - Effects of dietary lysine levels on performance and immune response of weanling pigs housed at two floor space allowances. AB - Three 35-d trials involving 288 crossbred weanling pigs (initial weight, 7.1 kg; age, 28 d) were used to determine the separate and interactive effects of two floor space allowances (.28 and .14 m2/pig) and three dietary lysine levels (NRC recommended, NRC+ .1% crystalline lysine-HCl, and NRC+ .2% crystalline lysine HCl) on growth performance and several factors that measure variation within pens. Each trial was conducted as a 2 x 3 factorial arrangement of treatments in a randomized complete block design. There were four pens (four pigs per pen) for each of the six treatment combinations in each trial. The lysine x floor space allowance interaction was not significant (P = .25) for daily gain, daily feed intake, or gain/feed. Restriction of the floor space allowance decreased (P < .001) daily gain and daily feed intake, but gain/feed was not affected. The humoral immune response, as measured by the level of antibodies produced after two injections of ovalbumin, was not affected by floor space allowance. Addition of .1 and .2% crystalline lysine-HCl improved daily gain (P < .07), gain/feed (P < .10), and humoral immune response (P < .05) and was without effect (P = .28) on feed intake. Natural logarithms of variance, coefficients of variation, and range of daily gain and body weights were not changed by floor space allowance or dietary lysine level. Pigs on adequate and restricted floor space allowances responded similarly to dietary lysine levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463137 TI - Delivery of lymph node-targeted adriamycin by gastric submucosal liposomal injection in rabbits. AB - We investigated the feasibility of specifically delivering adriamycin (ADR) to the regional lymph nodes via gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in a rabbit model. We determined the tissue distribution of ADR for up to 7 days after the gastric submucosal injection of Lipo-ADR (0.4 mg/kg of ADR potency) and i.v. administration of an equal dose of free adriamycin (F-ADR). The area under the ADR concentration-time curve (AUC) of the regional lymph nodes was 85.4 micrograms.day/g after gastric submucosal injection of Lipo-ADR and 8.44 micrograms.day/g after i.v. administration of F-ADR. The targeting index of the regional lymph nodes, defined as the ratio of the AUC after gastric submucosal injection of Lipo-ADR to the AUC after i.v. administration of F-ADR, was 10.1. Gastric submucosal injection of Lipo-ADR enhanced lymph node-specific delivery of ADR compared with i.v. administration of F-ADR. The targeting index was 0.47 for the heart, 0.25 for the bone marrow, and 0.41 for the spleen, indicating that gastric submucosal injection of Lipo-ADR reduced delivery of ADR to these organs, as compared with i.v. administration of F-ADR. These data demonstrate that gastric submucosal injection of Lipo-ADR is well suited for specific delivery of ADR to the regional lymph nodes, suggesting that this method of administration may be useful in delivering preoperative adjuvant chemotherapy for preventing gastric cancer recurrence. PMID- 8463140 TI - Influence of source and amount of dietary protein on performance, blood metabolites, and reproductive function of primiparous beef cows. AB - Forty Angus x Hereford 2-yr-old primiparous cows (358 kg) were used to determine the effects of source and amount of CP on performance, reproductive function, and metabolic status of suckled primiparous cows. A 2 x 2 factorial treatment arrangement was used; cows received either 100 or 150% of NRC recommendations for CP in diets that contained either soybean meal (low escape = L) or corn gluten meal/blood meal (high escape = H) as the principal supplemental protein source. Resulting treatments were 100-L, 100-H, 150-L, and 150-H. Cows were individually fed diets for 100 d or until they were observed to be in standing estrus. Diets were isoenergetic and limit-fed to meet NRC recommendations for NE, Ca, and P for 364-kg, 2-yr-old primiparous cows producing 4.5 kg of milk daily and gaining .23 kg/d. Increased CP tended (P = .09) to increase ADG in cows, but body condition score was unaffected. Increased CP and use of a CP source with higher potential for ruminal escape increased ADG in calves from d 0 to 97 (P = .002 and .04, respectively), which corresponded with numerical changes in milk production. Feeding high escape CP sources decreased plasma glucose and urea N (P = .04 and .0001, respectively). Increased CP tended (P = .12) to increase plasma glucose and increased (P = .0001) plasma urea N. Treatment had no effect on profiles of LH or progesterone. Although numerical differences in conception rate seemed large for 100-L compared with the remaining treatments, statistical significance was not detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463141 TI - Evaluation of long-term somatotropin implants in finishing pigs. AB - Ninety pigs were used to investigate the efficacy of long-term implants of porcine somatotropin (pST) in improving growth, feed:gain ratio, and carcass characteristics in pigs at three dose levels (0-, 100-, and 200-mg pST implant) from 71 to 99 kg live weight. The use of long-term implants did not alter (P > .05) growth rate. Administration of the 200-mg pST implant resulted in a 15% reduction in feed consumption, and this reduction was significant (P < .05). The feed:gain ratio was improved (P < .05) in pigs that received the 200- compared with 0-mg pST implant (3.2 vs 2.62 of kg feed/kg of gain). In pigs that received the 200- or 100-mg pST implant, there was a reduction (P < .05) in carcass weight; however, carcass length was similar (P > .05) regardless of pST treatment. Administration of the 200-mg pST implant resulted in 25 and 38% reductions (P < .05) in last rib fat and leaf fat compared with the 0-mg pST implant. The weights of kidneys and head were increased by the pST administration. The weights of wholesale cuts were not affected by the administration of the pST implant. However, separable skin and fat from the ham, loin, and picnic were lower (P < .05) in pigs that received the 200-mg pST than in pigs that received the 0-mg pST implant. Meat color and structure were similar across pST treatments, indicating that the use of long-term pST implants was not detrimental to meat quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463142 TI - Alternative methods of selection for litter size in mice: III. Response to 21 generations of selection. AB - Alternative methods of selection to increase litter size in mice have been practiced for 21 generations followed by six generations of relaxed selection. Three replicates were used with four selection criteria: index of components (IX:I = 1.21 x total ovulation rate + 9.05 x ova success), uterine capacity (UT), litter size (LS), and an unselected control (LC). In IX, ovulation rate and ova success were measured by number of corpora lutea and number of pups born/number of corpora lutea, respectively. In UT, uterine capacity was measured and defined as number of pups born to unilaterally ovariectomized (right ovary excised) females. Selection in LS was based on number born to unaltered dams. In all cases, number born was fully formed, live or dead pups. Pups from 16 randomly chosen LC dams and from the top 16 dams in IX, UT, and LS were selected to produce the next generation in each criterion-replicate line. Response in number born, selected criteria deviated from control, was regressed on generation number over the 21 generations of selection. Responses for the IX and LS criteria were quite similar (.14 +/- .01 and .16 +/- .01 pups per generation, respectively), whereas response in UT, with only one functional horn, was slightly lower (.09 +/ .01). The average cumulative selection differentials for IX, LS, and UT at Generation 21 were 32.78 index units, 36.38 pups, and 28.53 pups, respectively. The LC criterion had an unintentional cumulative selection differential of 3.3 pups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463143 TI - Potential shortcomings of output:input ratios as indicators of economic efficiency in commercial beef breed evaluations. AB - In recent years animal breeders have increasingly made use of output:input ratios and simple measures of economic efficiency, such as annual profits, as a basis for comparisons and evaluations of the commercial applicability of alternative beef breeds. In many instances, however, output:input ratios may produce fallacious indications of economic efficiency that may, in turn, lead to erroneous conclusions regarding the true commercial applicability of the breeds evaluated. Errors potentially arising from the use of output:input ratios in breed evaluations may be attributed to a combination of 1) a narrow range of input use values under which most breeds are evaluated and 2) the inability of output:input ratios, including average annual profitability, to reflect consistently the economic objectives of commercial cow-calf producers. An alternative basis for breed comparison and evaluation is, therefore, developed from economic theories related to optimal investment and asset replacement. Comparison of the results obtained with this alternative to those obtained from output:input ratio evaluation, including annual profitability, indicate that potential value differences of as much as 33% may result from the use of output:input ratios as a primary basis of commercial breed evaluation. PMID- 8463144 TI - Evaluation of mating systems involving five breeds for integrated beef production systems: IV. Accounting for variability and genetic trends. AB - Computer models were used to simulate integrated cow-calf-feedlot production systems. Angus (A), Charolais (C), Hereford (H), Limousin (L), and Simmental (S) purebreds and two- and three-breed rotational crossbreds were included. Models were deterministic and based on data reported primarily from the 1970s. Variation in carcass weights were determined to predict distributions of carcass weights and values for 272- to 318-kg carcasses. Data were updated to a 1984 base by increasing birth, weaning, yearling, and mature weights to account for genetic trends within breeds. Two slaughter end points were considered: 288-kg carcass weight and low Choice grade. At low Choice grade, accounting for variation in carcass weights around the 272- to 318-kg target weight increased the estimated efficiency of A and AH crosses (input costs/carcass value), whereas at the 288-kg end point, efficiency rankings among other breed combinations were relatively unchanged. Including genetic trends resulted in increased estimated efficiencies among breed combinations with previously underweight carcasses at low Choice (A and AH), measured either as input costs/carcass weight or lean weight values. Within breeds, accounting for genetic trends and variation for weights caused breeds to be ranked differently when evaluated at low Choice. PMID- 8463145 TI - Correlated responses in reproductive and carcass traits to selection for 200-day weight in Landrace pigs. AB - Correlated responses in reproductive and carcass traits from a line of Landrace pigs selected for increased 200-d weight along with a randomly selected control line were studied in 195 litters (109 select, 86 control) and 285 pigs (132 select, 153 control). Reproductive and maternal traits studied included litter sizes born, born alive, and alive at 21 d and litter weights at birth and at 21 d. Carcass traits studied were carcass length, longissimus area, average backfat thickness, 10th-rib backfat thickness, specific gravity, weights of closely trimmed ham, loin, and shoulder, belly weight, subjective scoring of the longissimus muscle for color and marbling, estimated percentage of muscle, and lean growth. Total weighted cumulative selection differential for 200-d weight over six generations was 88.7 kg. The realized heritability for 200-d weight was .26 +/- .08, and the change in 200-d weight was 4.2 +/- 1.3 kg per generation. None of the regression coefficients for reproductive traits differed significantly from zero. Ham weight, belly weight, marbling score, and lean growth increased by .069 +/- .027 kg, .051 +/- .020 kg, .045 +/- .012 points, and .0042 +/- .0007 kg/d, respectively, per generation. Specific gravity decreased by -.00063 +/- .00023 per generation in response to the selection for 200-d weight. The increase in lean growth in the select line was the result of an increased growth rate and not from an improvement in percentage of lean in carcasses from pigs from the select line. PMID- 8463146 TI - Effects of selection strategies using heifer pelvic area and sire birth weight expected progeny difference on dystocia in first-calf heifers. AB - A stochastic computer simulation model was developed to evaluate the effects of selection strategies based on heifer pelvic area and sire birth weight EPD on dystocia in first-calf heifers. Parameters and relationships used were taken from the literature. Unrelated sets of yearling heifers were simulated. Replacement heifer selection was based on breeding the top 40, 60, 80 or 100% (i.e., no selection) of available heifers as determined by yearling pelvic area (YRLGPA). Selected heifers were bred to bulls that were selected based on EPD for birth weight (SEPD). Levels of SEPD were -2.7, -1.8, -.9, 0, .9, and 1.8 kg. Simulated responses included precalving pelvic area, calf birth weight, calving difficulty score (1, 2, 3, 4), and incidence of dystocia (0, 1). Both measures of dystocia were predicted from the ratio of precalving pelvic area to calf birth weight. Simulated data were analyzed using least squares procedures. The effects of SEPD were significant (P < .05) for birth weight, calving difficulty score, and the frequency of dystocia. Differences among levels of heifer selection for YRLGPA were significant for YRLGPA, precalving pelvic area, birth weight, and calving difficulty score but not for the frequency of dystocia. Based on partial regressions calculated from weighted replication means, a 1-kg decrease in SEPD will decrease average calving difficulty score by .12 units and decrease the frequency of dystocia by 4%, whereas each 10% increase in selection pressure on YRLGPA will reduce the average calving difficulty score by only .02 units and have no detectable effect on the frequency of dystocia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463147 TI - Changes in ovulation rate, uterine capacity, uterine dimensions, and parity effects with selection for litter size in swine. AB - This study was conducted with random samples of pigs of a line (LS) selected for eight generations for litter size and a randomly selected control line (RS) in the Nebraska Gene Pool population and of crosses of these lines with a Large White-Landrace composite line (I) that was selected for an index of ovulation rate and embryonic survival to 50 d of gestation. Two experiments were done to obtain information on ovulation rate, uterine dimensions, and uterine capacity. In Exp. 1, 103 gilts were slaughtered 9 to 16 d after their second estrus to obtain reproductive tracts for evaluation of ovulation rate and uterine dimensions. In Exp. 2, unilateral hysterectomy-ovariectomy was performed 3 to 10 d after puberty in 109 gilts that were then mated at their next estrus and slaughtered at 93 to 100 d of gestation to recover reproductive tracts for evaluation. Litter size at birth was recorded at first (n = 414), second (n = 159), and third (n = 143) parity of pureline and crossline gilts. The cumulative response to eight generations of selection for litter size pooled over type of cross and parity was 1.21 +/- .38 pigs, in good agreement with the realized response of 1.06 pigs previously estimated for the period of selection. This response was due to an increase of 1.30 +/- .54 eggs in ovulation rate (measured by the number of corpora lutea in cyclic and pregnant gilts) and .66 +/- 1.28 pigs in uterine capacity (measured after unilateral hysterectomy-ovariectomy). No significant changes were found in uterine dimensions in cyclic gilts. Approximately 25% of the increase in litter size could be explained by a reduction in number of mummified pigs at birth, an indication that uterine capacity in late gestation was increased. Estimated differences between lines (gLS - gRS) were not significantly different for pureline and crossline gilts and sows, and no interactions of these estimates with parity were detected. Estimates of heterosis for LS x I and RS x I did not differ significantly, nor were interactions of heterosis with parity significant. PMID- 8463148 TI - The effects of different methods of estimating fecal output on plasma cortisol, fecal output, forage intake, and weight change in free-ranging and confined wethers. AB - Thirty-four white-face wethers (avg BW 56 kg) were used in two experiments to investigate differences in plasma cortisol, forage intake, fecal output, and BW change associated with two methods of estimating fecal output. The methods were fecal collection bags (B) and marker estimates of fecal output (U). A control treatment (C) was included in each experiment in which wethers were not bagged or dosed with the marker. Experiment 1 was conducted with wethers grazing dormant sagebrush-bunchgrass range. Experiment 2 was conducted with wethers housed in metabolism crates. In Exp. 1, the following differences were detected: 1) basal and mean integrated (following ACTH challenge) plasma cortisol levels were higher (P < .05) for U wethers than for C wethers, 2) no differences (P > .05) between B and C wethers were detected for basal or mean integrated plasma cortisol, 3) both B and U wethers gained (P < .05) weight, whereas C wethers lost weight, and 4) no differences (P > .05) between B and U wethers were detected for cortisol measurements, weight change, or fecal output. No differences (P > .05) were noted for any of the variables tested in Exp. 2. When treatments were combined within experiment to test Exp. 1 vs 2, time to peak cortisol levels was longer (P < .05) and mean integrated cortisol levels and weight change were lower (P < .05) for wethers in confinement than for wethers on range. No difference (P > .05) was detected for basal cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463149 TI - Comparison of the fatty acid composition of subcutaneous adipose tissue from mature Brahman and Hereford cows. AB - The fatty acid composition of adipose tissue was measured in 37 mature Brahman and 32 mature Hereford cows to determine breed effect. Diet was held constant among all cows. When biopsied, cows were on oats and native cool-season annual pastures of good quality. Real-time ultrasound measurements of subcutaneous fat were taken at three locations (between the 12th and 13th rib, at the rump, and at the perianal region) to determine overall fatness. Overall fat thickness from these measurements was 1.3 cm for Brahman cows and 1.7 cm for Hereford cows (P < .01). Subcutaneous adipose tissue biopsy samples were collected from the perianal region, and fatty acid composition was determined using a gas chromatograph. Fatty acids were expressed in both normalized (area percentage) and gravimetric (grams/100 grams of fresh tissue) formats. In addition to greater overall subcutaneous fat thickness, Hereford cows contained 5 g more of fatty acids per 100 g of fresh adipose tissue than Brahman cows (P < .05). Subcutaneous adipose tissue from Hereford cows was higher (P < .01) in total saturated fatty acids and lower in mono- and polyunsaturated fatty acids than subcutaneous adipose tissue from Brahman cows. Compositional differences remained when breeds were compared by analysis of covariance at a common body fatness. The data suggest a genetic basis for the differences in fatty acid composition of Brahman and Hereford cows. PMID- 8463150 TI - Growth and slaughter characteristics of ram and wether lambs implanted with zeranol. AB - Forty-nine Columbia ram and wether lambs born in April 1990 and 46 born in April 1991 were studied to determine the effects of zeranol implants on growth, difficulty of pelt removal, and carcass characteristics. Implanting ram and wether lambs once (1990) or twice (1991) with 12 mg of zeranol did not change live weight or ADG but gain/feed decreased (P < .05) in ram lambs slaughtered at approximately 50 kg. Testes weight was reduced approximately 50% by implanting. Two implants reduced (P < .05) the force needed to pull the pelt from the hind legs of ram lambs, but implanting tended to increase the force required to pull the pelt from wether lambs. Data for pelt weight, force required to pull the pelt, percentage of the carcass in the shoulder or splenius muscle, and Warner Bratzler shear values showed that zeranol implants resulted in ram lambs becoming more like wethers and wether lambs becoming more like rams. Implanting with zeranol did not affect closure of the metacarpal growth plate in ram or in wether lambs. Difficulty of pelt removal can be reduced by implanting ram lambs with 12 mg of zeranol at approximately 114 d of age and reimplanting zeranol 28 d later. PMID- 8463151 TI - Palatability of prerigor cooked boar meat. AB - Cooking reduces odor intensity in boar meat but also may induce lipid oxidation unless the meat pH is above approximately 6.0. This research was designed to determine the feasibility of cooking boar meat in the prerigor state to overcome boar odor and lipid oxidation problems. Prerigor and postrigor triceps brachii muscle samples from 40 boars (20 Duroc and 20 Yorkshire) were cooked to 60 degrees C, frozen and stored at -20 degrees C, reheated in a 60 degrees C water bath for 1 h, and then subjected to pH, thiobarbituric acid (TBA), and sensory analyses. Boar odor intensity and skatole concentration in backfat samples were determined by olfactory test and HPLC, respectively. Cooked (initial cooking) prerigor meat was found to have higher (P < .05) pH and lower (P < .05) TBA values than comparable postrigor meat (6.44 vs 6.09 and 2.15 vs 3.23, respectively). Regression analysis indicated an inverse relationship between pH and TBA values (r = -.52; P < .01). No appreciable changes in TBA values were noted after frozen storage for 14 to 98 d, but reheating increased TBA values (P < .05) in both prerigor and postrigor samples (3.45 vs 4.32, respectively). Sensory evaluation scores indicated that prerigor cooked meat was less tender with more pronounced rancid flavor than postrigor cooked meat (P < .05), but panelists may have allowed the toughness of the prerigor samples to adversely affect their flavor scores. No difference in boar odor was detected between rigor states or breeds. Mean skatole concentration in backfat was .12 micrograms/g and no difference was detected between breeds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463152 TI - Effect of supplemental niacin on sow reproduction and sow and litter performance. AB - In this study the effects of supplemental crystalline niacin on sow reproduction and sow and litter performance were evaluated using 240 litters produced by 67 sows. A basal 12.80% CP corn-soybean meal-oat diet was supplemented with 0 or 33 mg of crystalline niacin/kg during gestation and lactation. The sows were grouped to equalize initial BW and parity among the two treatment groups. Each sow was fed 2.0 kg/d during gestation and 1.8 kg plus .45 kg per nursing pig during lactation. Sows not culled due to reproductive or structural problems remained on the experiment for five parities (average 3.6). Supplemental niacin did not improve (P > .20) any of the sow reproductive or sow and litter performance variables evaluated, including the subjective scores for sow lameness, toe cracks, and hair and skin condition. In conclusion, these results suggest that a 12.80% CP corn-soybean meal-oat diet provides adequate niacin during gestation and lactation without supplementation with crystalline niacin. PMID- 8463153 TI - Effect of chromium picolinate on growth and serum and carcass traits of growing finishing pigs. AB - Three experiments were conducted to evaluate chromium picolinate (CrPic) in growing-finishing pigs. Treatments were replicated four times within each experiment with three pigs per replicate in Exp. 1 and four pigs per replicate in Exp. 2 and 3. Average initial weights were 37.8, 30.5, and 22.4 kg in Exp. 1, 2, and 3, respectively. In Exp. 1, the basal corn-soybean meal diet (B, 120% NRC Lys) was supplemented with 0, 25, 50, 100, or 200 ppb of Cr from CrPic. Daily gain was increased (Cr cubic, P < .02) and serum cholesterol decreased (Cr cubic, P < .08) by addition of CrPic. In Exp. 2, the basal diet was supplemented with 0, 100, 200, 400, or 800 ppb of Cr from CrPic. Daily gain and ADFI were decreased (Cr linear, P < .05) by CrPic. Serum cholesterol also was decreased (Cr quadratic, P < .05) by CrPic. Longissimus muscle area (LMA) and percentage of muscling (MUS) were increased (Cr quadratic, P < .01) and 10th rib fat (TRF) was decreased (Cr quadratic, P < .01) by CrPic. In Exp. 3, pigs were allotted to the following treatments: 1) B, 2) B + 1,467 ppb of picolinate (Pic), 3) B + 200 ppb of Cr from CrCl3.6H2O, 4) B + 1,467 ppb of Pic + 200 ppb of Cr from CrCl3.6H2O, 5) B + 100 ppb of Cr from CrPic, or 6) B + 200 ppb of Cr from CrPic. Longissimus muscle area and MUS were increased (P < .01) and TRF decreased (P < .01) in pigs fed CrPic but not in pigs fed CrCl3.6H2O and(or) Pic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463154 TI - Interrelationships between porcine somatotropin and dietary lysine on growth performance and carcass characteristics of finishing swine. AB - Seventy-two barrows (initial weight = 57.1 kg) were used to determine the interrelationship between porcine somatotropin (pST) and dietary lysine and their effects on growth performance and carcass characteristics. Pigs were injected daily in the extensor muscle of the neck with either 4 or 8 mg of pST and fed a pelleted corn-soybean meal-sesame meal diet (.8% lysine; 17.8% CP) or diets containing 1.0, 1.2, or 1.4% lysine provided by additions of L-lysine.HCl (2 x 4 factorial arrangement). Control pigs (placebo injection) received the .8% lysine diet. All diets were formulated to contain > or = 200% of current recommendations for other amino acids, vitamins, and minerals. A tendency for a pST x lysine interaction was observed for cumulative ADG (P < .15) and feed conversion (G/F; P < .05). Average daily gain and G/F were improved by increasing dietary lysine level in pigs injected with 4 mg/d of pST; however, pigs injected with 8 mg/d of pST had greater improvements in cumulative ADG and G/F with added lysine. Feed intake was reduced (quadratic, P < .10) as dietary lysine level and pST dosage increased. Increasing pST dosage and dietary lysine increased (linear, P < .05) longissimus muscle area and decreased backfat thickness. Trimmed ham and loin weights were increased (linear, P < .10) by pST dosage. Chemical composition of samples taken from the loin, ham, and belly indicated increased moisture and CP and decreased lipid content as pST dosage and dietary lysine level increased (quadratic, P < .05). Shear force values from loin and semimembranosus increased with increasing lysine level (quadratic, P < .01) and pST dosage (linear, P < .05); however, these differences were not detected by sensory analysis (P > .20). Plasma urea concentrations on d 28 decreased with increasing lysine level (quadratic, P < .05), and plasma lysine concentrations increased (linear, P < .01). Based on the pST x lysine interaction for ADG and G/F, these data suggest that the lysine level needed to maximize growth performance and carcass characteristics may be proportional to the pST dosage provided. Growth and carcass characteristics were maximized by dietary lysine intakes of 27 to 32 and > or = 36 g/d for pigs injected with 4 and 8 of mg/d of pST, respectively. PMID- 8463155 TI - Porcine somatotropin and dietary lysine influence bone mineralization and mechanical properties of bones in finishing swine. AB - The femur, a rib, and a third metacarpal were collected from 108 barrows (initial weight = 57 kg) and analyzed to determine the effects of porcine somatotropin (pST) and dietary lysine on bone mineralization and mechanical properties. In Exp. 1, pigs were injected daily with 4 mg of pST and fed diets containing 1.0% Ca and .9% P and either .6, .8, 1.0, 1.2, or 1.4% lysine. Control pigs (placebo injection) received the .6% lysine diet. Bone wall thickness (BWT) of the femur increased (linear, P < .05) but ash content decreased (linear, P < .10) as dietary lysine level increased. Stress and ash content of the rib also decreased (linear, P < .05) with increasing dietary lysine level. In Exp. 2, pigs were injected with either 4 or 8 mg/d of pST and fed diets containing 1.1% Ca and 1.0% P and either .8, 1.0, 1.2, or 1.4% lysine. Control pigs received the .8% lysine diet. Increasing pST dosage increased BWT of the femur (linear, P < .10) but decreased ash content (linear, P < .10). In the rib, increasing pST dosage reduced stress, modulus of elasticity (linear, P < .10), and ash content (linear, P < .01). Increasing lysine level resulted in increased BWT of the femur and decreased ash content of rib, femur, and metacarpal (linear, P < .10). These data indicate that pST administration in conjunction with increasing lysine levels decreases bone ash content but increases BWT of finishing pigs. PMID- 8463156 TI - Reduction of fertility and alteration of uterine pH in heifers fed excess ruminally degradable protein. AB - The objective of these studies was to elucidate the causes underlying the reduction of fertility associated with feeding of excess ruminally degradable protein to cattle. Holstein heifers were fed total mixed rations that either met (Normal) or exceeded (High) ruminally degradable protein requirements. In Exp. 1 heifers (n = 80) were inseminated at estrus after being fed the experimental diets for 4 wk. First-service conception rates were 82 and 61% for the Normal and High groups, respectively (P < .05). Plasma urea nitrogen (PUN) levels were elevated (10.2 +/- .17 vs 14.8 +/- .19 mg/dL) in the High group throughout the experiment (P < .05). In Exp. 2, heifers (n = 32) receiving the same diets as in Exp. 1 were fitted with catheters in a jugular vein, in the bladder, and in the uterus on either the day before expected estrus or d 6 after estrus. On estrus or d 7, plasma and urinary NH4 and urea nitrogen and uterine pH were determined at 4 h intervals for 24 h beginning just before feeding. Plasma NH4 was variable and did not differ between treatments or days of the estrous cycle. During the 24-h period, urinary urea nitrogen and PUN were elevated (P < .05) in the High groups and did not differ between days of the cycle. Urinary NH4 excretion was elevated (P < .05) during the 24-h period only in the High group on d 7. Uterine pH did not change over time after feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463157 TI - Alterations of pH in response to increased dietary protein in cattle are unique to the uterus. AB - This study was undertaken with two objectives: 1) to determine whether the effect of excess dietary protein on intrauterine pH in cattle is specific to the uterus or manifested in other bodily fluids and 2) to determine whether the effect of excess ruminally degradable protein on uterine pH can be ameliorated by substitution with a less-degradable protein source. Thirty-six Holstein cows in early lactation were fed isoenergetic total mixed rations that either 1) met undegradable intake protein (UIP) and degradable intake protein (DIP) requirements (Balanced), 2) met DIP requirements and exceeded UIP requirements by 25% (High UIP), or 3) met UIP requirements and exceeded DIP requirements by 25% (High DIP). After diets had been fed > or = 2 wk, uterine, blood, salivary, and urinary pH and plasma urea nitrogen were determined at estrus (d 0) and d 7. Plasma urea nitrogen (mg/dL) was not different between estrus and d 7 but was significantly affected by diet (Balanced, 16.1 +/- 2.3; High UIP, 19.2 +/- 1.6; High DIP, 22.3 +/- 2.6; P < .05). There was no effect of treatment on the pH of any fluid measured at estrus: intrauterine, blood, salivary, and urinary pH averaged 6.84 +/- .05, 7.39 +/- .01, 8.30 +/- .05, and 8.15 +/- .05, respectively. In contrast, on d 7, uterine pH was significantly lower in both high-protein groups, regardless of protein degradability (Balanced, 7.13 +/- .05; UIP, 6.95 +/- .04; DIP, 6.85 +/- .05; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463158 TI - Sperm transport and distribution during the puberal transition in ewe lambs. AB - Sperm transport through and distribution within the anterior reproductive tract were evaluated at either 2 or 22 h after artificial insemination in ewe lambs at first (1E; n = 15) or third (3E; n = 14) estrus and in mature (MAT; n = 12) ewes. Each ewe was inseminated immediately upon detection of estrus with 7.5 x 10(8) progressively motile sperm placed into the external os cervix. Ewes were hysterectomized at either 2 or 22 h after insemination. Sperm were recovered from the uterus, isthmi, and ampullae by flushing with sterile .9% saline. The distribution of sperm recovered from the uterus, isthmus, and ampulla did not differ (P > .10) among 1E, 3E, and MAT ewes at either 2 or 22 h. However, there was a tendency (P = .08) for more sperm to be recovered from the anterior reproductive tract in 3E and MAT ewes than from that in 1E ewes. There was a time of hysterectomy x anatomical segment interaction (P < .05) for percentage of sperm recovered of the total number of sperm in the inseminate because more sperm were recovered from the isthmus and ampulla at 22 h than at 2 h after insemination. Percentages of 1E, 3E, or MAT ewes from which sperm were recovered from the anterior reproductive tract did not differ (P > .10). However, sperm were recovered from the oviducts in a greater (P < .05) percentage of ewes at 22 h after insemination than at 2 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463159 TI - Effects of sire and dam on late-pregnancy conceptus and hormone traits in beef cattle. AB - Forty-six primiparous F1 heifers produced from mating Brahman (B), Charolais (C), Jersey (J), Longhorn (L), or Shorthorn (S) sires to crossbred cows were bred by AI to one of two Angus sires selected to produce high (H) or moderate (M) fetal growth. Dams were slaughtered at an average of 231 d of gestation. Daily blood samples were obtained from the dam on d 228 to 231 to determine serum estradiol, progesterone, and testosterone concentrations. Pelvic height was greatest (P < .05) in B, C, and L and pelvic width was greatest (P < .05) in S, C, and J dams, but pelvic areas did not differ (P > .10). Dams with greater hip height had larger pelvic areas (r = .45; P < .01). Intact fetuses from C and S dams were heaviest (P < .05), those from S dams had the greatest (P < .05) head width, and heart girth was greatest (P < .05) in fetuses from L dams. Fetuses from H sires were greater in weight (P < .01), body length (P < .01), and cannon circumference (P < .01). Dam differences were found in fetal heart weight (P < .01), trimmed placental membrane weight (P < .01), and average placentome weight (P < .05). Weights of eviscerated fetuses were greatest from C dams (P < .05). Placentome number was lowest (P < .05) in J dams, but J dams had the highest (P < .05) average placentome weight. Interactions between fetal genotype and breed of maternal environment were found for weight of eviscerated fetus (P < .05), body length, and heart weight (P < .01) and resulted from both magnitude and direction of change in the sire effect. The H sire increase in fetal weight was greatest in J dams, whereas B dams allowed expression of the fetal growth potential but at a lower level. Fetal trait interactions were also found for breed x sex and sex x sire (P < .05 to P < .01) and were due to the magnitude of differences expressed between the M and H sires. Serum testosterone concentrations were highest (P < .05) in B and L dams, dams gestating fetuses sired by the H sire (P = .08), and those with male fetuses (P < .01). We interpret these results to indicate that some maternal environments can suppress fetal growth, whereas others seem to complement the growth and allow maximum expression of the fetal genetic growth potential.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463160 TI - Uptake of orally administered beta-carotene by blood plasma, leukocytes, and lipoproteins in calves. AB - The uptake of beta-carotene by blood cells, plasma, and lipoproteins was studied in bull calves that were orally administered a single (Exp. 1; n = 18 Angus calves) or multiple (Exp. 2; n = 16 Holstein calves) doses of beta-carotene. Administration of beta-carotene increased plasma beta-carotene and the amount of beta-carotene associated with each lipoprotein fraction. Before beta-carotene treatment, the total amount of beta-carotene associated with the high-density lipoprotein (HDL) was three- to fourfold higher than the amount associated with low-density lipoprotein (LDL) and fivefold higher than the amount associated with very-low-density lipoprotein (VLDL). The relative increase in total beta-carotene associated with the lipoproteins was greater for LDL than for HDL or VLDL. Orally administered beta-carotene increased the uptake of beta-carotene by lymphocytes. Subcellular fractions of blood lymphocytes isolated from animals fed beta carotene revealed that beta-carotene was taken up in significant amounts by the mitochondrial, nuclear, and microsomal fractions. The profile of beta-carotene uptake by these subcellular fractions did not mirror that observed in plasma. In contrast, beta-carotene was not detectable in blood neutrophils and erythrocytes in either beta-carotene-supplemented or unsupplemented calves. Treatment did not influence the concentrations of retinol or alpha-tocopherol in plasma, lipoproteins, lymphocytes, neutrophils, or erythrocytes. These data revealed the presence of beta-carotene in bovine lymphocyte subcellular fractions and suggest a possible physiological role of beta-carotene in these cells. PMID- 8463161 TI - Protein sources for finishing calves as affected by management system. AB - Two beef production systems were evaluated in conjunction with an evaluation of escape protein sources for finishing calves. Two hundred forty crossbred steers and 80 crossbred heifer calves (BW = 267 +/- 2 kg) were split into two groups: 1) control, finished (207 d) after a 3-wk feedlot adjustment period and 2) grazing cornstalks for 74 d after a 3-wk feedlot adjustment period, then finished (164 d). Finishing treatments were sources and proportions of supplemental CP: 1) urea 100%; 2) soybean meal (SBM) 100%; 3) blood meal (BM) 50%, urea 50%; 4) feather meal (FTH) 50%, urea 50%; 5) SBM 50%, FTH 25%, urea 25%; 6) SBM 25%, FTH 38%, urea 37%; 7) FTH 25%, BM 25%, urea 50%, and 8) FTH 38%, BM 13%, urea 50%. Treatments 1 to 8 were fed in dry-rolled corn (DRC)-based diets. Treatments 9 and 10 were supplement Treatments 1 and 7 fed in diets based on high-moisture corn. Calves finished after a 74-d period of grazing cornstalks consumed more feed (P < .01) and gained faster (P < .01) but were less efficient (P < .05) than calves finished directly after weaning. Although not statistically different, calves finished after grazing cornstalks and supplemented with natural protein in the feedlot were 7% more efficient than calves supplemented with urea alone. Efficiency of calves finished directly after weaning was similar for calves supplemented with natural protein or urea alone. Supplementing SBM/FTH/urea or BM/FTH/urea improved feed efficiency compared with supplementing FTH/urea alone. These data suggest that allowing calves to graze cornstalks before finishing is a possible management option, but this system may require more metabolizable protein in the finishing diet to maximize feed efficiency if the calves are expressing compensatory growth. PMID- 8463162 TI - Technical note: an improved method to quantify nonesterified fatty acids in bovine plasma. AB - Nonesterified fatty acids (NEFA) are measured routinely in the study of nutrition and growth physiology. To improve the efficiency with which this variable is measured, a two-reaction, enzymatic-based assay was adapted and validated to quantify NEFA in bovine blood plasma using 96-well microtiter plates. The effects of incubation time, temperature, and of sample volume were examined in addition to possible interfering substances, recovery, reagent stability, and range of linearity. Incubation for 30 min at 21 degrees C for each of the two reactions resulted in maximal slope and r2 values (1.94 and .999, respectively). Percentage of recovery was 107% when using 5 microL and 100% when using 10 microL of heparinized bovine plasma in the assay. Uniform linear standard curves (r2 > .99) were obtained using reagents stored at 4 degrees C for 9 d. An equal volume of 1 mM acetate, propionate, valerate, and butyrate added to plasma did not affect results. The assay was linear from 125 to > 1,000 microEq/L. Intra- and interassay CV for the 5-microL sample volume were 3.6 and 3.7%, respectively. This modified assay provides results comparable to the standard assay yet reduces reagent and labor requirements and increases sample capacity. PMID- 8463163 TI - Growth and endocrine responses of cattle to implantation of estradiol-17 beta during continuous or discontinuous grazing of high- and low-endophyte-infected tall fescue. AB - Forty-eight Angus x Hereford steers (initial BW = 336 +/- 8.3 kg) were used in a 56-d study to evaluate growth and endocrine responses to continuous or discontinuous grazing of high-endophyte-infected Kentucky-31 (K; > 57% infestation rate) or low-endophyte-infected Johnstone tall fescue (J; < 1% infestation rate) and implantation with 0 or 24 mg/steer of estradiol-17 beta (E2; Compudose). Steers were allotted by weight to eight 3-ha paddocks (four paddocks of each fescue variety) with six steers per paddock. Two paddocks of each variety were grazed continuously (KK and JJ), whereas steers on the remaining four paddocks were rotated every 14 d from K to J (KJ) or from J to K (JK). Three steers in each paddock were implanted with E2 on d 0. The study extended from May 25, 1988 to July 20, 1988 with steers exposed to potential heat stress conditions for 52 d of the 56-d study. Body weights were obtained on d 0, 28, and 56, and blood samples were taken on d 28 and 56. Overall ADG, serum prolactin, and serum alkaline phosphatase activity were greater (P < .05) in JJ than in KK steers. Rotation from K to J did not increase overall ADG, prolactin, insulin-like growth factor I (IGF-I), or alkaline phosphatase activity compared with the continuously grazed KK, whereas JK steers had lower (P < .10) ADG, prolactin, and alkaline phosphatase activity than JJ steers. Estradiol-17 beta increased (P < .10) IGF-I in JJ, KJ, and JK steers but not in KK steers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463164 TI - Effect of sire and dam breed on copper status of fat lambs. AB - To determine the effect of breed on copper status of crossbred (F1) lambs, a study was conducted using 187 crossbred wether lambs. Wether lambs were progeny of five ram breeds (Dorset, Finnsheep, Montadale, Romanov, and Texel) and two ewe breeds (Rambouillet and a composite breed [1/2 Columbia, 1/4 Suffolk, 1/4 Hampshire]). Diets were adjusted to decrease crude protein twice during the experimental period, with analyzed copper levels for the three diets of 5.2, 4.4, and 3.6 ppm. All means were adjusted to a constant carcass weight of 27.265 kg using a covariate analysis. Least squares means of the liver copper concentration for sire breeds ranged from 307 to 458 micrograms/g on a DM basis. Romanov- (307 micrograms/g) and Finnsheep-sired (327 micrograms/g) lambs had the lowest liver copper concentration, whereas Montadale- (359 micrograms/g) and Dorset-sired (360 micrograms/g) lambs were intermediate and Texel-sired (458 micrograms/g) lambs were significantly higher compared with other lamb breeds. Least squares means for total liver copper for the five ram breeds ranged from 69 to 101 mg. Finnsheep- (69 mg), Romanov- (72 mg), and Montadale-sired (80 mg) lambs were lowest, Dorset-sired (85 mg) lambs were intermediate, and Texel-sired (101 mg) lambs were higher (P < .02) compared with other lamb breeds for total liver copper. Least squares means for serum copper ranged from .86 to 1.05 ppm. Levels of serum copper were similar for Montadale- (.86 ppm), Finnsheep- (.90 ppm), Texel- (.93 ppm), and Dorset-sired (.94 ppm) lambs and higher (P < .02) for Romanov-sired (1.05 ppm) lambs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463165 TI - Is an objective assessment of antibiotic therapy in exacerbations of chronic bronchitis possible? PMID- 8463166 TI - New directions in the diagnosis and treatment of pelvic inflammatory disease. PMID- 8463167 TI - Nitroimidazole drugs--action and resistance mechanisms. II. Mechanisms of resistance. PMID- 8463168 TI - Distribution of genes encoding erythromycin ribosomal methylases and an erythromycin efflux pump in epidemiologically distinct groups of staphylococci. AB - Erythromycin-resistant staphylococci can be divided into two phenotypic classes based on their pattern of cross-resistance to other macrolides, lincosamides and type B streptogramins. Strains inducibly or constitutively resistant to all MLS antibiotics possess erythromycin ribosomal methylase (erm) genes, whereas strains inducibly resistant to only 14 and 15-membered ring macrolides and type B streptogramins harbour msrA, which encodes an ATP-dependent efflux pump. Dot-blot hybridization was used to study the distribution of ermA, ermB, ermC and msrA in five epidemiologically distinct groups of staphylococci. The most widely distributed resistance determinant was ermC, which was detected in 112 (50.6%) of 221 isolates, alone in 106 isolates and in combination with a second erythromycin resistance determinant in six strains. MsrA was detected in 73 (33%) of isolates, alone in 65 and in combination with a methylase gene in eight strains. This determinant was responsible for erythromycin resistance in over one-third (36.4%) of clinical isolates of coagulase-negative staphylococci. ErmA and ermB were present in only a minority of isolates (5.9 and 7.2% of strains, respectively). The resistance determinants present in ten strains did not hybridize to any of the four probes although, in all cases, their resistance phenotype was consistent with the possession of a methylase gene. Interestingly, ermB was found exclusively in animal isolates of Staphylococcus intermedius, Staphylococcus xylosus and Staphylococcus hyicus, but not in coagulase-negative staphylococci of human origin. This determinant has previously only been found in a small number of epidemiologically related strains of Staphylococcus aureus. PMID- 8463169 TI - A membrane-bound precursor beta-lactamase in strains of Moraxella catarrhalis and Moraxella nonliquefaciens that produce periplasmic BRO-1 and BRO-2 beta lactamases. AB - By employing the non-ionic detergent Triton X-100, a membrane-bound beta lactamase was extracted from strains of Moraxella (Branhamella) catarrhalis and Moraxella nonliquefaciens that produce BRO-1 and BRO-2 beta-lactamases. Unlike BRO-1 and BRO-2, which exhibit multiple major bands on isoelectric focusing (IEF), the membrane-bound enzyme focused as a single IEF band at a pI of 6.20, which was not present with either of the other two enzymes. The membrane-bound beta-lactamase could be extracted from all strains producing BRO-1 and BRO-2, including recombinant strains constructed by transformation or conjugation. The enzyme was also recovered from Escherichia coli strain HB101 carrying vector plasmid pLQ521 into which the BRO-1 beta-lactamase gene from M. catarrhalis had been cloned. All three beta-lactamases were indistinguishable by inhibitor profiles with clavulanic acid, BRL 42715, sulbactam and tazobactam. These data suggested that all three beta-lactamases were the product of a single gene in Moraxella spp., and that the membrane-bound beta-lactamase serves as a precursor of both BRO-1 and BRO-2. Species differences in cellular processing of the membrane-bound enzyme could explain the minor differences in IEF patterns that occurred with BRO-1 and BRO-2 beta-lactamases when present in different species. PMID- 8463170 TI - Effects of imipenem on Escherichia coli studied using bioluminescence, viable counting and microscopy. AB - The effects of imipenem on the growth of Escherichia coli ATCC 25922 were studied using a bioluminescence assay of bacterial ATP, microscopy and viable counting in iso-osmotic Mueller-Hinton broth (MHB) and hypo-osmotic nutrient broth (NB). Imipenem showed a post-antibiotic effect (PAE) of > 2 h for E. coli in both MHB and NB after 2 h exposure to 1 and 8 mg/L of imipenem when determined by bioluminescence and microscopy. The intracellular ATP level increased after 2 h exposure of E. coli to 1 mg/L of imipenem in MHB. In this culture there was a predominance of spheroplasts. These spheroplasts were large and osmotically fragile and a 10 min treatment in water-diluted MHB (hypo-osmotic) prior to the assays lysed the large spheroplasts. This reduced the intracellular ATP level and shortened the PAE when determined by bioluminescence, and caused more rapid initial killing and a negative PAE when determined by viable counting. At 8 mg/L imipenem in MHB and at all concentrations in NB there was a predominance of rods and only a small number of spheroplasts which all disappeared when the cultures resumed logarithmic growth. In these cultures there was a significant initial decrease in intracellular ATP. This study showed reasonable agreement between microscopy and bioluminescence, which are direct methods, for determining the initial killing and PAE of imipenem on E. coli. More rapid initial killing and shorter or no PAEs, were in general, obtained in both MHB and NB when determined by viable counting. However, the effective regrowth time, defined as the time for the bacterial density to increase 1 log10 from the pre-exposure inoculum, was independent of the method used for measuring regrowth in both MHB and NB. PMID- 8463171 TI - A novel antimicrobial central venous catheter impregnated with benzalkonium chloride. AB - Catheter-related sepsis is a common complication associated with the use of central venous catheters (CVC). In an attempt to overcome this problem benzalkonium chloride was incorporated into a CVC polymer. The effect of the presence of benzalkonium chloride on microbial colonization of the CVC was then assessed in vitro. MICs and MBCs of benzalkonium chloride for a range of organisms were performed and good activity against Gram-positive organisms was confirmed. In order to assess the antimicrobial activity of the benzalkonium chloride-impregnated catheter, 2 cm lengths were placed on to nutrient agar plates inoculated with various micro-organisms. Zones of inhibition against five strains of Staphylococcus epidermidis and two strains of Staphylococcus aureus were demonstrated. Smaller zones of inhibition was also produced with Gram negative species and Candida albicans. The zone sizes correlated with the MICs. Bacterial adherence to the benzalkonium-chloride-impregnated catheters was determined in both static and dynamic models and was significantly reduced compared with control catheters, containing no antimicrobial agent (P < 0.01). Inhibition of microbial adherence to benzalkonium-chloride-impregnated catheters placed in 25% human blood in phosphate-buffered saline (PBS), for up to seven days or PBS alone for 14 days was detected. The findings indicate that benzalkonium-chloride-impregnated catheters exhibit reduced microbial colonization by a range of organisms in vitro. The incorporation of benzalkonium chloride into a CVC may thus offer an effective method for the prevention of catheter related sepsis. PMID- 8463173 TI - Rapid fluorometric measurement of the intra-cellular concentration of ciprofloxacin in mouse peritoneal macrophages. AB - A simple fluorometric assay requiring only a single sample of cells to determine the number of cells, from the DNA linked to the fluorochrome 4',6-diamidino-2 phenylindol (DAPI), and the uptake of ciprofloxacin, a natural fluorescent quinolone is described. Mouse peritoneal macrophages were found to concentrate ciprofloxacin up to 12.7 (+/- 1.5)-fold. Combined fluorometry provides a precise, sensitive method for determining the intracellular concentration of fluoroquinolones, as well as that of naturally fluorescent or fluorochrome-linked drugs. PMID- 8463172 TI - Susceptibility of 170 penicillin-susceptible and penicillin-resistant pneumococci to six oral cephalosporins, four quinolones, desacetylcefotaxime, Ro 23-9424 and RP 67829. AB - MICs of six oral cephalosporins (cefdinir, cefpodoxime, cefaclor, cefuroxime, cefixime and Ro 40-6890), four quinolones (ciprofloxacin, ofloxacin, OPC-17116 and fleroxacin), desacetylcefotaxime, Ro 23-9424 (a fused combination of fleroxacin + desacetylcefotaxime) and RP 67829 (a benzonaphthyridine) were determined for 49 penicillin-susceptible (S), 38 penicillin-intermediate (I), and 83 penicillin-resistant (R) strains of Streptococcus pneumoniae. All MICs were determined by a standardized agar dilution method utilizing Mueller-Hinton agar supplemented with sheep blood. MIC90s of OPC-17116 and RP 67829 were < or = mg/L, and were unaffected by penicillin-susceptibility. MICs of all beta-lactams increased with increasing penicillin-MICs, with cefdinir, cefpodoxime, cefuroxime and Ro 40-6890 being the most active compounds, followed by cefaclor and cefixime. MIC90s of ciprofloxacin and ofloxacin were 2 mg/L. MIC90s of Ro 23-9424 were lower than those of either parent compound (fleroxacin 8 mg/mL for all three groups; desacetylcefotaxime 0.5 mg/mL [S], 0.5 mg/mL [I], 4 mg/mL [R]; Ro 23-9424 0.125 mg/L [S], 0.25 mg/L [I], 0.5 mg/L [R]). The results indicated that several newly introduced and experimental antimicrobials have potential for the treatment of infections caused by resistant strains of S. pneumoniae. PMID- 8463174 TI - Comparative chemotherapeutic activity of temafloxacin, cefoxitin, clindamycin, imipenem and ampicillin/sulbactam against Bacteroides fragilis in a mouse subcutaneous abscess model. AB - The new fluorinated 4-quinolone temafloxacin was compared with cefoxitin, clindamycin, imipenem (with or without cilastatin) and ampicillin/sulbactam in a mouse subcutaneous abscess model of Bacteroides fragilis infection. Based upon in vitro susceptibility data, temafloxacin may represent an effective oral and parenteral alternative to standard oral and parenteral anti-anaerobic agents currently in use. Temafloxacin therapy with dosage regimens of < 200 mg/kg/day typically yielded 2-3 x log10 reductions in cfu/abscess, similar to ampicillin/sulbactam, while cefoxitin and clindamycin were generally unable to produce similar reductions at doses up to 400 mg/kg/day. Imipenem (with or without cilastatin) was unable to produce a 1 x log10 reduction at doses of 400 mg/kg/day. This study suggests that temafloxacin has potential for the treatment of anaerobic or mixed aerobic-anaerobic infections in man. PMID- 8463175 TI - A comparison of the cost of ceftazidime therapy and gentamicin combinations in three UK hospitals. PMID- 8463176 TI - MIC audit for routine ciprofloxacin sensitivity testing. PMID- 8463177 TI - Antistaphylococcal activity of vancomycin and teicoplanin under anaerobic conditions. PMID- 8463178 TI - Increasing prevalence of resistance to ampicillin, penicillin and vancomycin of enterococci isolated from blood cultures during 1990-1991. PMID- 8463179 TI - Immortalization of human mammary epithelial cells by SV40 large T-antigen involves a two step mechanism. PMID- 8463180 TI - Measurement of strain in cultured bone and fetal muscle and lung cells. PMID- 8463181 TI - Mitogens in bovine pituitary for cultured rat tracheal cells. PMID- 8463182 TI - Synergistic inhibition of human rhabdomyosarcoma cells by sodium phenylacetate and Tretinoin. PMID- 8463183 TI - Liposomes can specifically target entrapped melanin to hair follicles in histocultured skin. PMID- 8463184 TI - Stability of a murine hybridoma is dependent on the clonal line and culture media. PMID- 8463185 TI - Extracellular calcium does not contribute to cryopreservation-induced cytotoxicity. AB - The possible role of extracellular calcium ([Ca+2]e) in cryopreservation-induced cytotoxicity was tested using Madin-Darby canine kidney (MDCK) cells and a fluorescent multiple endpoint assay. MDCK cells maintained in 2 mM [Ca+2]e and treated with the calcium ionophore, ionomycin, increased their intracellular calcium ([Ca+2]i) as revealed by the calcium indicator dye, Fluo3 and the bottom reading spectrofluorometer, CytoFluor 2300. The addition of 10 mM [ethylene bis (oxyethylenenitrilo)]-tetraacetic acid (EGTA) to the extracellular medium before treatment with ionomycin blocked this ionomycin-dependent increase in [Ca+2]i. A number of site and activity-specific fluorescent probes were surveyed to determine which indicator dye might best reveal the ionomycin-induced cytotoxic events during this increase in [Ca+2]i. Although most dyes changed their emission profiles in response to calcium, neutral red was found to best reflect the loss of [Ca+2]i homeostasis. The NR50 for a 15-min exposure to ionomycin in the presence of 2 mM [Ca+2]e was approximately 2 microM ionomycin, but ionomycin had little apparent effect on neutral red retention when 10 mM EGTA was added to the extracellular medium. Thus it was clear that an increase in [Ca+2]i could be cytotoxic to MDCK cells and that neutral red could monitor this cytotoxic episode. To test if [Ca+2]e was similarly cytotoxic during cryopreservation, MDCK cells were subjected to cryopreservation in the presence of dimethylsulfoxide (DMSO). In contrast to previous studies, plasma membrane integrity, not lysosomal function, seemed to best correlate with cell survival subsequent to cryopreservation. In addition, decreasing [Ca+2]e had no discernable effect on the retention of plasma membrane indicator dyes, neutral red, or cell survival. It is concluded that a) plasma membrane indicator dyes, not neutral red, might be better indicators of cytotoxicity occurring during cryopreservation; b) DMSO might be toxic to lysosomes during cryopreservation of cultured cells; and c) although [Ca+2]e can contribute to cytotoxicity, the presence of [Ca+2]e might not influence cryopreservation-induced cytotoxicity. PMID- 8463186 TI - Nickel-induced increases in gap junctional communication in the uterine cell line SK-UT-1. AB - Previous studies have suggested that gap junctions may have a role in various uterine functions, including parturition. Because nickel has been demonstrated to increase uterine contractility in vitro, the effect of nickel (II) chloride on gap junctional communication was assessed in a tumorigenic uterine cell line, SK UT-1 (ATCC HTB 114). Cells were exposed in vitro to 25 and 50 microM NiCl2 for 24 h or 100 microM NiCl2 for 3, 12, and 24 h, then functional gap junctional communication was measured as the transfer of Lucifer yellow dye from microinjected donor cells to their primary neighbor cells. Dye transfer was significantly increased only in cell cultures exposed to 100 microM NiCl2 for 24 h, compared to untreated controls, lower doses, and shorter exposure periods. This response was inhibited by the simultaneous co-treatment of SK-UT-1 cells with magnesium by adding 100 microM MgSO4 to the dosing medium. Possible mechanisms and implications for these findings are discussed. PMID- 8463187 TI - Absence of trypsinogen autoactivation and immunolocalization of pancreatic secretory trypsin inhibitor in acinar cells in vitro. AB - To establish the significance of the addition of trypsin inhibitors to pancreatic acinar cells maintained in vitro, cells were cultured in the presence or absence of soybean trypsin inhibitor. Both cultures exhibited similar growth pattern, ultrastructural appearance, as well as secretory properties. Moreover, there was no evidence of trypsinogen activation in the culture medium. Using the immunocytochemical approach, pancreatic secretory trypsin inhibitor antigenic sites were revealed with specific polyclonal and monoclonal antibodies. The results obtained demonstrated that this trypsin inhibitor is in fact a typical pancreatic secretory protein being processed through the endoplasmic reticulum Golgi-granule secretory pathway of the acinar cells in rat and human tissues. While the polyclonal antibody yield labelings of increasing intensities along the secretory pathway, the monoclonal one probably due to the molecular nature of its specific antigenic determinant, gave higher labelings in the endoplasmic reticulum. In conclusion the present study has shown that pancreatic acinar cells secrete a specific pancreatic trypsin inhibitor which most probably is involved in the mechanism to prevent trypsinogen activation. PMID- 8463188 TI - Epidermal growth factor and insulin-like growth factor-1 preserve cell viability in the absence of protein synthesis. AB - Prolonged exposure of cells to the potent protein synthesis inhibitor cycloheximide (CHX) terminates in cell death. In the present study we investigated the effect of epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin on cell death induced by CHX in the human cancerous cell lines MDA-231 and MCF-7 (breast), KB (oral epidermoid), HEP-2 (larynx epidermoid), and SW-480 (colon), and correlated this effect to the inhibition rate of protein synthesis. Cell death was evaluated by measuring either dead cells by trypan blue dye exclusion test or by the release of lactic dehydrogenase into the culture medium. CHX was shown to induce cell death in a concentration (1 to 60 micrograms/ml) and time (24 to 72 h)-dependent manner in each of the five cell lines. EGF at physiologic concentrations (2 to 40 ng/ml) reduced cell death close to control level (without CHX) in the cell lines HEP-2, KB, MDA-231, and SW 480, but had almost no effect on cell death in the MCF-7 cells. IGF-1 at physiologic concentrations (2 to 40 ng/ml) reduced cell death nearly to control level in the MCF-7 cells, but had only a partial effect in the other four cell lines. Insulin at supraphysiologic concentration (10,000 ng/ml) mimicked the effect of IGF-1 in each of the cell lines. CHX at concentrations that induced about 60% cell death, inhibited about 90% of protein synthesis as measured by [3H]leucine incorporation. Protein synthesis remained inhibited although cell viability was preserved by EGF or IGF-1. These results indicated that the mechanism by which EGF or IGF-1 preserve cell viability does not require new protein synthesis and may be mediated via a posttranslational modification effect. PMID- 8463189 TI - Fetal bovine serum and other sera used in tissue culture increase epithelial permeability. AB - Fetal bovine serum (FBS) or heat-inactivated FBS (56 degrees C for 30 min, HFBS) caused a dose-dependent decrease in the transepithelial electrical resistance of an epithelial monolayer (MDCK). A saturating concentration of HFBS (30%) caused an average fall of 25 +/- 2% within 60 min. Upon removal of HFBS, the resistance returned to its starting value within 1 h. Flux studies with [3H]mannitol demonstrate that the fall in resistance is due to an increased permeability of the tight junctions. Thirty percent heat inactivated sera from goat, newborn calf, calf, bovine, and horse caused falls ranging from 26 to 47%. In contrast with the basolateral preference of human and bovine adult sera, fetal bovine and newborn calf sera elicit this response primarily by interacting with the apical surface of the epithelium. HFBS-treated monolayers show a significant increase in the condensation of F-actin at points where > or = 3 cells meet. These results demonstrate that FBS and other sera used as nutritional supplements can increase the permeability of the tight junctions of cultured epithelial cells. PMID- 8463190 TI - Culturing of primary hepatocytes as entrapped aggregates in a packed bed bioreactor: a potential bioartificial liver. AB - Conventional culture systems for hepatocytes generally involve cells cultured as flat, monolayer cells, with limited cell-cell contact, in a static pool of medium, unlike the liver in vivo where the parenchymal cells are cuboidal, with extensive cell-cell contact, and are continuously perfused with blood. We report here a novel bioreactor system for the culturing of primary hepatocytes with cuboidal cell shape, extensive cell-cell contact, and perfusing medium. The hepatocytes were inoculated into the bioreactor and allowed to recirculate at a rate optimal for them to collide and form aggregates. These newly-formed aggregates were subsequently entrapped in a packed bed of glass beads. The bioreactor was perfused with oxygenated nutrient medium, with controlled oxygen tension, pH, and medium perfusion rate. The hepatocytes were viable for up to the longest time point studied of 15 days in culture based on urea synthesis, albumin synthesis and cell morphology. Light microscopy studies of hepatocytes cultured for 15 days in the bioreactor showed interconnecting three-dimensional structures resembling the hepatic cell plate in the liver organ. Electron microscopy studies on the same cells revealed ultrastructure similar to the hepatocytes in vivo, including the presence of plentiful mitochondria, rough and smooth endoplasmic reticulum, glycogen granules, peroxisomes, and desmosomes. We believe that our hepatocyte bioreactor is a major improvement over conventional culture systems, with important industrial applications including toxicology, drug metabolism, and protein/peptide synthesis. The hepatocyte bioreactor concept may also be used as the basis for the development of a bioartificial liver to provide extracorporeal hepatic support to patients with hepatic failure. PMID- 8463191 TI - Visual orienting deficits in high-functioning people with autism. AB - There has been renewed interest in the idea that attentional dysfunction may underlie autistic symptomatology (e.g., Bryson, Wainwright-Sharp, & Smith, 1990; Dawson & Lewy, 1989a, 1989b). Existing research indicates problems with overfocused attention (Lovaas et al., 1971; Rincover & Ducharme, 1987), and with shifting attention between sensory modalities (Courchesne et al., 1990). These phenomena were examined further by using Posner's (1978) visual orienting task with a group of high-functioning autistic adolescents and adults, and matched normal controls. Our results indicate that autistic people have difficulty processing briefly presented cue information. Evidence of problems disengaging and shifting attention within the visual modality was also provided. The findings can be seen as consistent with previous behavioral, autonomic, and electrophysiological research which has revealed impairments in the registration, processing, and response to external stimuli. PMID- 8463192 TI - Nonverbal expression in autism of Asperger type. AB - Short unstructured social interactions between a volunteer interviewer, an adult with autism of Asperger type, and a control subject with a schizoid personality disorder were video-recorded. Asperger subjects tended to look less at the other person, to make more self-stimulatory gestures, and to look at the interviewer significantly less than normal subjects, and substantially less than schizoid subjects, during the periods when the interviewer was vocalizing although there were no such differences when the interviewer was listening. We suggest that the gaze avoidance of autism may in actuality be a lack of expected gaze (e.g., gaze when the other person is talking) rather than an absolute avoidance, and suggest that a lifelong absence of gaze response to social cues including speech could explain a number of the developmental features of autism including lack of joint attention with others, lack of understanding and affective response to others, and poor discrimination of facial expressions. PMID- 8463193 TI - Trajectory of adaptive behavior in males with fragile X syndrome. AB - Adaptive behavior in males with fragile X syndrome was longitudinally examined in 17 subjects, ages 1 to 17. Subjects received adaptive behavior evaluations on two occasions within one of three age periods. All domains of the Vineland Adaptive Behavior Scales increased from youngest to oldest age groups, yet older subjects (ages 10 to 17) showed significant declines in their adaptive behavior scores from first to second testing. A relative strength in Daily Living Skills and weakness in Socialization emerged only among older subjects. There was a significant relationship between adaptive behavior and mental age scores in all subjects. Discussion emphasized the parallels between declines in IQ and adaptive behavior as well as the need for further research on adaptive skills in young adults with fragile X syndrome. PMID- 8463194 TI - Depression and social adjustment in siblings of boys with autism. AB - Compared 22 siblings of autistic boys and 34 other siblings on measures of depression, social adjustment, and the amount of child care and domestic responsibility the siblings carry within the family. The relationship between sibling gender, age, birth order, qualities of the boy with autism, and family characteristics, and siblings' scores on the above measures were examined. Results of this research showed that siblings of autistic boys scored significantly higher on depression than the comparison group, but not on problems of social adjustment. There were no statistically significant gender differences; however, different gender-related patterns emerged on the correlates which may be of theoretical significance for future studies. PMID- 8463196 TI - Brief report: a case study assessing the validity of facilitated communication. PMID- 8463195 TI - Auditory brainstem responses in autism: brainstem dysfunction or peripheral hearing loss? AB - The advent of electrophysiological techniques for audiologic and neurologic assessment in the late 60s has generated at least 11 auditory brainstem response (ABR) studies in autism designed to test the integrity of the auditory brainstem pathways. The results reported are contradictory, involving prolongation, shortening, and no abnormalities in central transmission latencies. When sample and methodological factors influencing the ABR are taken into consideration in the interpretation of results, the ABR data available at present can be seen as only suggestive, rather than supportive, of brainstem involvement in autism. Paradoxically, these studies revealed the presence of peripheral hearing impairment in a non-negligible number of autistic individuals. Additional evidence of auditory abnormalities as well as the implications for the clinician are considered. PMID- 8463197 TI - Brief report: facilitated communication with adults with autism. PMID- 8463198 TI - Brief report: vocabulary development in an autistic boy. PMID- 8463199 TI - Brief report: lack of response in an autistic population to a low dose clinical trial of pyridoxine plus magnesium. PMID- 8463200 TI - Brief report: low frequency of the fragile X syndrome among Japanese autistic subjects. PMID- 8463201 TI - Contextual probability evaluation in autistic, receptive developmental language disorder, and control children: event-related brain potential evidence. AB - Compared 8- to 14-year-old children with either autism or receptive developmental language disorder (RDLD) to age- and IQ-matched normal controls in their ability to detect both frequent (p = .70) and infrequent (p = .30) randomly presented auditory stimuli under task and no-task conditions. Event-related brain potentials (ERPs), behavioral reaction times, and target detection accuracy rates were measured. Although the three groups of children performed in a similar manner on behavioral measures, only the children with autism demonstrated an abnormally small amplitude of the P3b, a component of the ERP. This result is interpreted in terms of (a) the consistency of this finding with other ERP studies involving older individuals with autism; and (b) its significance with respect to the difficulty children with autism have in modifying their expectancies to contextually relevant sequences of auditory information. PMID- 8463202 TI - Hypothalamic-pituitary-adrenal axis function in children with attention-deficit hyperactivity disorder. AB - Examined hypothalamic-pituitary-adrenal axis (HPA axis) function in 30 children with attention-deficit hyperactivity disorder (ADHD) by measuring the diurnal variation and response to the dexamethasone suppression test (DST) of saliva cortisol. Normal diurnal saliva cortisol rhythm was found in only 43.3% of the ADHD children. DST showed suppression in 46.7% of the ADHD children. An abnormal diurnal rhythm and nonsuppression to the DST were more frequent in the severely hyperactive group than in the mildly were more frequent in the severely hyperactive group than in the mildly hyperactive group of children with ADHD. These results suggest abnormalities in HPA axis function in some children with ADHD, especially those exhibiting severe hyperactivity. PMID- 8463203 TI - Receptor inhibition by immunoglobulins: specific inhibition by autistic children, their relatives, and control subjects. AB - Forty-two parents of children with autistic disorder, 15 children with autistic disorder, 17 siblings of children with autistic disorder, and 12 unrelated normal adult controls were studied to determine if immunoglobulins isolated from their plasma would inhibit binding of the 5HT1A agonist, [3H]-8-hydroxy-N,N-dipropyl-2 aminotetralin (DPAT) to 5HT1A receptors in human hippocampal membranes. There were no significant differences among the means of percentage inhibition of DPAT binding of parents, children with autistic disorder, siblings, or unrelated controls. In addition, there were no differences in the proportion of subjects with > 15% DPAT inhibition among autistic children, their parents, their siblings, or unrelated controls. Immunoglobulin inhibition was not specific for the 5HT1A receptor binding site, since immunoglobulins inhibited binding to 5HT2, D1, D2, and alpha 2-adrenergic binding sites. The immunoglobulins isolated from normal controls inhibited [3H]-rauwolscine binding at alpha 2-adrenergic sites less than immunoglobulins of children with autistic disorder and their parents and siblings. This study did not support the hypothesis that autoantibodies to 5HT1A or 5HT2 receptors are characteristic of autistic disorder. PMID- 8463204 TI - Self-injurious behavior in Rett syndrome: interactions between features of Rett syndrome and operant conditioning. AB - Operant and biological theories of the cause of self-injurious behavior (SIB) in people with a mental handicap are often viewed as mutually exclusive. In this single case study, interactions between features of Rett syndrome and operant conditioning as determinants of SIB are examined. Functional analysis by analog methodology indicated different functions for two forms of SIB shown by the subject: automatic reinforcement by sensory stimulation and escape from social interactions. It is suggested that features of Rett syndrome established conditions under which operant conditioning of self-injurious responding was maximized. The implications of this interaction between features of syndromes and operant conditioning for the conceptualization of the cause of SIB are discussed and it is proposed that the notion of a unitary cause of SIB is inappropriate. It is more productive to consider operant conditioning as the process that maintains responding against a background of predisposing and mediating factors which may be biologically determined. PMID- 8463205 TI - Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes. PMID- 8463206 TI - Formation of inter- and intramolecular disulfide bonds can activate cardiac troponin C. AB - Troponin C regulates contraction in striated muscle by alternating between the Ca(2+)-bound and apo conformations. We report here that spontaneous formation of an intramolecular disulfide bond between Cys-35 and Cys-84, or dimerization via an intermolecular disulfide bond between Cys-84 in cardiac troponin C, renders the protein Ca(2+)-independent when assayed in fast skeletal muscle myofibrils but to a much lesser extent in cardiac myofibrils. Formation of the intramolecular disulfide bond appears to expose hydrophobic surfaces, as indicated by an increase in fluorescence from hydrophobic fluorescent dyes, but does not alter the affinity of Ca(2+)-binding site II. These disulfide bonds constrain the protein into a conformation that either resembles or can substitute for the Ca(2+)-bound form of cardiac troponin C in fast skeletal muscle myofibrils. PMID- 8463207 TI - Demonstration of protein tyrosine phosphatase activity in the second of two homologous domains of CD45. AB - It has been reported that alteration of deletion of critical residues within one of the two homologous protein tyrosine phosphatase (PTPase)-like domains of CD45 completely abolishes all activity, suggesting that only the more N-terminal domain is catalytically active. However, we now demonstrate, by two independent techniques, that the second (C-terminal) domain is also a viable phosphatase. Limited proteolysis by endoproteinase Lys-C or trypsin increased the phosphatase activity toward reduced, carboxymethylated, and maleylated lysozyme approximately 8-fold. A 50-kDa fragment, isolated by ion exchange chromatography, was found to be responsible for this activity. N-terminal sequencing revealed that this fragment includes less than half of the first phosphatase domain and most, if not all, of the second. In a second experiment, 109 residues, including the presumed catalytic region, were removed from domain I by site-directed mutagenesis. Expression of this construct in a mammalian cell line resulted in increased PTPase activity over nontransfected control cells. Isolation of the recombinant CD45 by immunoprecipitation and immunoaffinity chromatography revealed that it had phosphatase activity. Both of these experimental approaches demonstrate that the second conserved PTPase domain of CD45 is a functioning PTPase, but that external regulation may be required to express its activity in the context of the native molecule. PMID- 8463208 TI - Alternative splicing gives rise to a nuclear protein tyrosine phosphatase in Drosophila. AB - A novel Drosophila protein tyrosine phosphatase gene (dPTP61F) undergoes alternative splicing to encode two non-receptor-like proteins of 61,000 daltons. This splice selection occurs at the 3' end of the message, altering the carboxyl termini of the encoded proteins. These carboxyl-terminal sequences govern the targeting of each protein tyrosine phosphatase either to a cytoplasmic membrane or to the nucleus. The catalytic activity of the two protein products is indistinguishable, suggesting that substrate specificity is modulated by the protein's subcellular location. PMID- 8463209 TI - Mutations in the catalytic subunit of the cAMP-dependent protein kinase interfere with holoenzyme formation without disrupting inhibition by protein kinase inhibitor. AB - Three amino acids were identified in the catalytic (C) subunit of the cyclic AMP dependent protein kinase that are involved in interaction with regulatory (R) subunit, but not with the specific protein kinase inhibitor, PKI. In a functional assay for gene induction, a C expression vector with serine or arginine substituted for Leu-198 and the double mutant C, His-87-->Gln/Trp-196-->Arg (Orellana, S. A., and McKnight, G. S. (1992) Proc. Natl. Acad. Sci, U.S.A. 89, 4726-4730), retained activity in the presence of an excess of RI or RII. In contrast, cotransfection of a full-length PKI expression vector completely inhibited the activity of both mutant and wild type C subunits. These data suggest that although the substrate/pseudosubstrate sites of R and PKI interact with C at the catalytic site, there is an additional domain on the C subunit that is involved in holoenzyme formation with R subunit and is distinct from sites specifying high affinity PKI binding. PMID- 8463210 TI - Tyrosine phosphorylation of pp125FAK by the aggregation of high affinity immunoglobulin E receptors requires cell adherence. AB - The aggregation of the high affinity IgE receptor (Fc epsilon RI) in adherent rat basophilic leukemia (RBL-2H3) cells induces the tyrosine phosphorylation of several proteins. We examined whether focal adhesion-associated tyrosine kinase, pp125FAK, is one of these proteins. Anti-pp125FAK monoclonal antibody immunoblotted and precipitated a 115-kDa tyrosine-phosphorylated protein. In the absence of Fc epsilon RI aggregation, pp125FAK was tyrosine-phosphorylated only in adherent cells. Aggregating Fc epsilon RI in adherent cells markedly enhanced tyrosine phosphorylation of pp125FAK. This increase was detectable within 1 min of Fc epsilon RI aggregation and was maximal by 15 min. In contrast, in nonadherent cells Fc epsilon RI aggregation did not induce tyrosine phosphorylation of pp125FAK. The enhanced influx of calcium by calcium ionophore or the activation of protein kinase C by phorbol myristate acetate induced tyrosine phosphorylation of pp125FAK only in adherent cells. Thus, Fc epsilon RI induced tyrosine phosphorylation of pp125FAK could be mediated by the activation of protein kinase C and/or the induction of calcium influx. The data indicate that cell adherence is essential for Fc epsilon RI-induced tyrosine phosphorylation of pp125FAK. PMID- 8463211 TI - Ligand diffusion in the distal heme pocket of myoglobin. A primary determinant of geminate rebinding. AB - There are at least two picosecond kinetic components in the rebinding of NO to native sperm whale myoglobin. Petrich et al. (Petrich, J. W., Lambry, J.-C., Kuczera, K., Karplus, M., Poyart, C., and Martin, J.-L. (1991) Biochemistry 30, 3975-3987) attribute the slowing of the reaction to a movement of the iron atom out of the plane of the heme following ligand dissociation. In contrast, Gibson et al. (Gibson, Q. H., Regan, R., Elber, R., Olson, J. S., and Carver, T. E. (1992) J. Biol. Chem. 267, 22022-22034) have explained multiphasic geminate reactions by diffusion of NO into the distal heme pocket as determined by its detailed structure. O2 and NO rebinding to iron and cobalt derivatives of native, V68F, and V68I sperm whale myoglobin has been examined. Each iron protein shows a biphasic time course of NO rebinding reactions with widely different rates and amplitudes. Although cobalt does not move out of the plane of the porphyrin on ligand removal, the reactions of the iron and cobalt derivatives of each protein were closely similar. The time course of O2 rebinding to cobalt was also similar to that of NO rebinding to iron. These results are consistent with a primary role for the structure of the distal pocket in determining diffusion of ligands away from the metal atom and as a result the time course of picosecond ligand rebinding. PMID- 8463212 TI - Interaction cloning of protein kinase C substrates. AB - We have previously used an overlay assay technique to detect proteins that interact with protein kinase C (PKC) (Hyatt, S. L., Klauck, T., and Jaken, S. (1990) Mol. Carcinogenesis 3, 45-53). In some cases, binding proteins were also identified as substrates. Therefore, we used the overlay assay approach to screen a rat kidney lambda gt11 cDNA library to isolate and identify additional PKC substrates. Two clones have now been characterized. 35A is the rat homologue of the myristoylated alanine-rich C kinase substrate (MARCKS)-related F52 cDNA, whereas 35H is a partial cDNA with substantial homology to the 3' end of beta adducin. Both cDNAs encode proteins that bind phosphatidyl-serine (PS) and are substrates for PKC. Phosphorylation decreased both PS and PKC binding activities. Both proteins contain high density positive charge domains similar to that found in the major PKC substrate MARCKS. These results demonstrate that PKC interactions with certain substrate proteins are of sufficiently high affinity to facilitate their isolation via interaction cloning. PMID- 8463213 TI - Serine- and threonine-rich domain regulates internalization of muscarinic cholinergic receptors. AB - Upon agonist exposure, most membrane receptors internalize into the cell as part of an adaptation process. Receptor domains that mediate internalization have been defined for several receptor classes, e.g. growth factor and transport receptors, but not yet for any of the numerous members of the family of G protein-coupled receptors (GPCRs), having seven putative transmembrane helices. With the use of deletion mutations, we previously showed that a small region in the middle of the third intracellular loop (i3) appears to be required for the agonist-induced internalization of the Hm1 muscarinic cholinergic receptor (Lameh, J., Philip, M., Sharma, Y. K., Moro, O., Ramachandran, J., and Sadee, W. (1992) J. Biol. Chem. 267, 13406-13412). Using point mutations, we now demonstrate that domain 286-292 (ESLTSSE) is required, with TSS playing a crucial role. Although the i3 loops of GPCRs share minimal overall sequence identity, even among closely related subtypes, small domains containing multiple S/T residues are also present in several other GPCRs, e.g. peptide, catechol, and all the muscarinic cholinergic receptor subtypes. S/T-->A mutations in analogous i3 domains also prevented receptor internalization in the case of Hm3 and attenuated internalization of Hm2. We propose that an S/T-rich domain in the i3 loop, possibly via phosphorylation reactions, regulates one pathway of GPCR internalization. PMID- 8463214 TI - Binding-incompetent adenovirus facilitates molecular conjugate-mediated gene transfer by the receptor-mediated endocytosis pathway. AB - Molecular conjugate vectors may be constructed that accomplish high efficiency gene transfer by the receptor-mediated endocytosis pathway. In order to mediate escape from lysosomal degradation, we have incorporated adenoviruses into the functional design of the conjugate. In doing so, however, we have introduced an additional ligand, which can bind to receptors on the cell surface, undermining the potential for cell specific targeting. To overcome this, we have treated the adenovirus with a monoclonal anti-fiber antibody, which renders the virus incapable of binding to its receptor. The result is a multi-functional molecular conjugate vector, which has preserved its binding specificity while at the same time being capable of preventing lysosomal degradation of endosome-internalized conjugate-DNA complexes. This finding indicates that adenoviral binding is not a prerequisite for adenoviral-mediated endosome disruption. PMID- 8463215 TI - Peptides derived from a sequence within beta 3 integrin bind to platelet alpha IIb beta 3 (GPIIb-IIIa) and inhibit ligand binding. AB - Peptides derived from a sequence within the loop structure of human platelet glycoprotein (GP) IIIa (integrin beta 3) were previously shown to inhibit fibrinogen binding to purified GPIIb-IIIa. In this study a series of peptides based on the GPIIIa sequence 211-221 (SVSRNRDAPEG) was synthesized. The most active peptide was determined to be RNRDA, and its inhibitory potency was 4-fold greater (IC50 = 4.8 microM) than that of SVSRNRDAPEG. These GPIIIa peptides also inhibited the binding of two monoclonal antibodies, pl-55 and PAC-1, which are directed against the activated conformer of GPIIb-IIIa. To determine whether these peptides bound directly to GPIIb-IIIa, an affinity matrix was prepared by coupling RNRDAPEGC to Sepharose. Fibrinogen or purified GPIIb-IIIa was applied to the affinity column. Only GPIIb-IIIa was retained on the column, and it could be specifically eluted by GPIIIa peptide or RGDV but not by an irrelevant peptide. Additionally, we observed that the binding of GPIIIa peptides to purified GPIIb IIIa induced exposure of a neoepitope on GPIIb that was recognized by the monoclonal antibody pl-80. These data suggest that sequences within the loop structure of GPIIIa can interact with the ligand binding domain of GPIIb-IIIa. Thus, this GPIIIa domain may be involved in regulating the accessibility of ligands to GPIIb-IIIa following platelet activation. PMID- 8463216 TI - K(+)-dependent Na+/Ca2+ exchange in human platelets. AB - Ca2+ influx via Na+/Ca2+ exchange was examined using fura-2 fluorescence techniques in human platelets loaded internally with Na+ by pretreatment with ouabain. In 140 mM LiCl, Ca2+ influx via the exchanger was completely dependent upon the presence of extracellular K+ (Km approximately 1 mM). In 140 mM N-methyl D-glucamine (NMDG), Ca2+ influx was stimulated by K+ but was not absolutely dependent upon it; the inclusion of 20 mM NaCl in the NMDG medium restored the K+ dependence of Ca2+ influx. Stimulation of Ca2+ influx by K+ was confirmed by 45Ca2+ flux studies. 86Rb+ fluxes were measured to determine if Ca2+ and Rb+ were co-transported by the exchanger. The presence of extracellular Ca2+ stimulated 86Rb+ influx in ouabain-treated platelets in 160 mM LiCl or NMDG. The Rb+/Ca2+ influx ratio was 0.42 +/- 0.04 (n = 3) at [Rb+] = 0.2 mM and 0.89 at [Rb+] = 1.3 mM. Neither K(+)-dependent Ca2+ influx nor Ca(2+)-dependent Rb+ influx was observed in 160 mM NaCl or in platelets that had not been pretreated with ouabain, indicating that these fluxes resulted from Na+/Ca2+ exchange activity. Na(+)-dependent Ca2+ efflux was also shown to be dependent upon the presence of internal K+. These properties are similar to those of the Na+/Ca(2+)-K+ exchanger found in retinal rods, as distinct from the more widely distributed cardiac-type exchanger. PMID- 8463217 TI - Isolation of the non-myristoylated form of a major substrate of protein kinase C (MARCKS) from bovine brain. AB - A substrate protein of protein kinase C with an apparent molecular mass of 70 kDa has been purified from bovine brain. This protein shares several properties with a major substrate of protein kinase C (myristoylated alanine-rich C kinase substrate; MARCKS). It is heat-stable and copurifies with MARCKS during various steps (ammonium sulfate precipitation and gel filtration). However, its elution from a calmodulin affinity column is different from that of MARCKS. It can be eluted by high ionic strength in the presence of calcium, whereas MARCKS can be eluted only in the absence of calcium. Its earlier elution from a reversed phase column suggests that p70 is less hydrophobic than MARCKS. The electrospray mass spectrum revealed an actual mass of 31,550 +/- 6.5 Da, very far from the apparent molecular mass in SDS-polyacrylamide gel electrophoresis (70,000 Da). This mass is about 200 Da smaller than that of MARCKS determined by mass spectrometry analysis (Manenti, S., Sorokine, O., Van Dorsselaer, A., and Taniguchi, H. (1992) J. Biol. Chem. 267, 22310-22315), close to the value expected for the change due to N-terminal myristoylation (210 Da). N-terminal amino acid sequencing showed that the N terminus is not blocked, and the sequence found for the 10 first amino acids is identical to that deduced from the cDNA sequence of bovine MARCKS. These data clearly establish that this protein is a non-myristoylated form of MARCKS and that the absence of the myristoyl moiety at the N terminus lowers the affinity to calmodulin. The purification performed both from the membrane and the cytoplasmic fractions of bovine brain indicated that this non-myristoylated form represents 20-30% of the MARCKS protein in the cytoplasmic fraction, and less than 5% in the membrane one. PMID- 8463218 TI - Cloning of a human gene, PIG-F, a component of glycosylphosphatidylinositol anchor biosynthesis, by a novel expression cloning strategy. AB - The glycosylphosphatidylinositol (GPI)-anchored proteins are widely distributed in eukaryotic cells, from yeasts to mammals. A number of proteins, such as glycosyltransferases, are necessary for GPI anchor biosynthesis. Cloning of genes encoding these proteins is required for analyses of their nature and the biosynthetic pathway. Here we report a new method of expression cloning that is applicable to many mutant rodent and human cells, and its application for cloning a human cDNA termed PIG-F (for Phosphatidyl-Inositol-Glycan class F) using a Thy 1-negative mutant murine thymoma cell line of complementation class F. PIG-F takes a part in the step of transfer of ethanolamine phosphate to the GPI intermediate containing three residues of mannose. This expression cloning strategy is applicable to the identification of not only other genes involved in GPI anchor biosynthesis but also human disease-associated genes using mutant mammalian cell lines. PMID- 8463219 TI - ATP-stimulated tetraethylammonium transport by rabbit renal brush border membrane vesicles. AB - These studies examined the ability of ATP to stimulate transport of the organic cation tetraethylammonium (TEA) into proximal tubular brush border membrane vesicles. ATP markedly enhanced TEA uptake for 1 h or more to values severalfold above those observed in the absence of ATP. The poorly hydrolyzable analogue of ATP, AMP-PNP (adenyl-5'-yl imidodiphosphate), reduced the effect of ATP but alone did not stimulate TEA uptake. GTP and ITP also stimulated TEA uptake, whereas other nucleotides did not. ATP-stimulated TEA uptake was saturable, temperature dependent, and markedly reduced by the organic cations amiloride, quinidine, cimetidine, and verapamil, but only modestly reduced by the organic cations N' methylnicotinamide and choline. Some inhibitors of other transport ATPases, including N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, and oligomycin, reduced the effect of ATP, whereas ouabain, vanadate, and azide did not. 4,4' Diisothiocyanatostilbene-2,2'-disulfonic acid also reduced TEA uptake in the presence of ATP. Vinblastine, but not actinomycin D and colchicine (all inhibitors of P-glycoprotein-mediated transport), reduced TEA uptake. The reduction of TEA transport by amiloride and cimetidine was most consistent with competitive inhibition, whereas the inhibition produced by N-ethylmaleimide and vinblastine evidently was not. ATP also stimulated uptake of N' methylnicotinamide but not that of vinblastine. These studies have identified a previously unrecognized process by which ATP hydrolysis may directly energize the reabsorption of organic cations from the renal tubule lumen. PMID- 8463220 TI - Uteroferrin and intracellular tartrate-resistant acid phosphatases are the products of the same gene. AB - Uteroferrin (Uf) is a purple acid phosphatase with a bi-iron center. It is the major secretory product of the porcine uterus under the influence of progesterone and supplies iron to the developing fetuses during pregnancy. Tartrate-resistant acid phosphatases (TRAP) are clearly similar to Uf in many of their properties but are generally located intracellularly in lysosomes. To determine whether Uf and intracellular TRAP are distinct gene products, cDNA for the TRAP from pig spleen were compared with Uf cDNA. Although no full-length cDNA for the former were isolated, a TRAP cDNA of 1.1 kilobases was identical in nucleotide sequence to a Uf cDNA (1.42 kilobases) in the region of overlap, which included the entire 3'-end of the transcript and most of the open reading frame. TRAP purified from porcine spleen also had an NH2-terminal amino acid sequence that corresponded to that of Uf purified from uterine secretions and was also similar in sequence to intracellular TRAP isolated from tissues of other species, including ones from human osteoclastomas and spleen. Finally, Southern hybridization analysis with two probes specific for exons 1 and 2 of the Uf gene strongly suggested the presence of only a single gene for acid phosphatases of this class in the pig. A similar analysis performed on human DNA with an exon-specific probe for human TRAP was also consistent with a single gene. It is concluded that the difference in trafficking between a secreted TRAP, such as Uf, and TRAP located in lysosomes is not the result of distinctive primary sequence of the polypeptides and that the variability within species ascribed to such enzymes is most likely the result of minor posttranslational changes. PMID- 8463221 TI - Ricin-resistant Madin-Darby canine kidney cells missort a major endogenous apical sialoglycoprotein. AB - gp114 is a major sialoglycoprotein expressed on the apical membrane of Madin Darby canine kidney (MDCK) II cells. We investigated its distribution in two lectin-resistant mutant cell lines derived from MDCKII cells, MDCKII-RCAr and MDCKII-ConAr cells. gp114 was present on the apical membrane of MDCKII-ConAr cells but was predominantly basolateral in MDCKII-RCAr cells. No change of polarity was observed for several apical and basolateral markers in this cell line. Reversal of polarity of gp114 mainly resulted from a modification of its intracellular sorting. gp114 showed altered endocytosis in MDCKII-RCAr cells. In MDCKII cells gp114 was slowly endocytosed, whereas in MDCKII-RCAr cells endocytosis of gp114 was highly increased. Using mannosidase I and II inhibitors we found that N-glycosylation only slightly affects gp114 sorting and endocytosis. Our results suggest that gp114 or an associated component in MDCK RCAr fails to express apical information or that a mutation creates a basolateral sorting signal which could be related to endocytic signals. PMID- 8463222 TI - Elimination of the hydroxyl groups in the ribose ring of ATP reduces its ability to phosphorylate the sarcoplasmic reticulum Ca(2+)-ATPase. AB - 2'-Deoxyadenosine 5'-triphosphate, 3'-deoxyadenosine 5'-triphosphate, and 3' amino-3'-deoxyadenosine 5'-triphosphate were substituted for ATP in the Ca2+ pumping cycle of the sarcoplasmic reticulum Ca(2+)-ATPase. The rate of phosphorylation of the enzyme decreased by more than an order of magnitude when either of the hydroxyl groups was eliminated from the ribose ring. This resulted in low rates of hydrolysis and low levels of phosphoenzyme intermediate. In addition, the Km(1) of hydrolysis and the K1/2 of phosphorylation of the derivatives modified in the 3' position were decreased by a factor of 5-10. Otherwise, the 3'-amino-3'-deoxyadenosine 5'-triphosphate was utilized in a manner equivalent to ATP. Because the observed rates of phosphoenzyme formation with the deoxynucleotides were lowered to the extent that they would be rate limiting in the enzyme cycle, and the level of phosphoenzyme intermediate remained low when the enzyme was back-inhibited by high Ca2+ concentrations, it was concluded that the majority of the enzyme remained in a preliminary conformation, in which the phosphorylation reaction could not proceed although substrate and Ca2+ were bound. It was then proposed that, following Ca(2+) induced changes in conformation, the hydroxyl groups are able to form hydrogen bonds with pertinent segments of the phosphorylation domain, helping to stabilize an enzyme-substrate complex, one function of which may be to provide the proper stereochemistry for phosphate transfer. PMID- 8463223 TI - Biochemical analysis of rab9, a ras-like GTPase involved in protein transport from late endosomes to the trans Golgi network. AB - rab9 is a ras-like GTPase which has been implicated in the transport of mannose 6 phosphate receptors between late endosomes and the trans Golgi network. We have expressed recombinant rab9 in Escherichia coli, purified the protein to homogeneity, and initiated a biochemical analysis of this enzyme. rab9 hydrolyzed GTP with a rate constant of 0.0052 min-1 at 37 degrees C. rab7, a highly homologous endosomal GTPase, hydrolyzed GTP with a rate constant of 0.0023 min-1 at 37 degrees C. At this temperature, GDP and GTP each dissociated from rab9 with first-order rate constants of 0.017 min-1. GDP and GTP dissociated from rab7 at 37 degrees C with first-order rate constants of 0.0054 and 0.0024 min-1, respectively. We modified the procedure of John et al. (John, J., Sohmen, R., Feuerstein, J., Linke, R., Wittinghofer, A., and Goody, R. (1990) Biochemistry 29, 6058-6065) for the preparation of nucleotide-free ras such that the procedure can now be applied to 1000-fold smaller quantities of protein. Using this method, we prepared microgram quantities of nucleotide-free rab9 in a form which is heat stable, free of exogenous nucleotide-degrading enzymes and which can be stored at -80 degrees C. At 37 degrees C for GDP and GTP, the second-order rate constants for association with nucleotide-free rab9 were 1.7 x 10(6) M-1 s-1 and 1.2 x 10(5) M-1 s-1, respectively, and equilibrium binding constants were 170 pM and 2.4 nM, respectively. PMID- 8463224 TI - Kinetic and stereochemical comparison of wild-type and active-site K145Q mutant enzyme of bacterial D-amino acid transaminase. AB - D-Amino acid transaminase (EC 2.6.1.21), from Bacillus sp. YM-1, a thermostable enzyme with pyridoxal 5'-phosphate as coenzyme and a target for the design of novel antimicrobial agents, catalyzes the reversible transfer of an amino group between D-alanine and alpha-ketoglutarate to form pyruvate and D-glutamate, respectively. To explore the catalytic role of Lys-145, which binds the coenzyme, a site-specific mutant enzyme, K145Q (in which Lys-145 had been mutated to glutamine) constructed earlier (Futaki, S., Ueno, H., Martinez del Pozo, A., Pospischil, M. A., Manning, J. M., Ringe, D., Stoddard, B., Tanizawa, K., Yoshimura, T., and Soda, K. (1990) J. Biol. Chem. 265, 22306-22312) was compared to the wild-type enzyme for its kinetic parameters. Initial velocity studies and partial reaction isotope exchange experiments showed that the low activity of the mutant enzyme (about 1.5% the activity of the wild-type enzyme with saturating substrates) is an intrinsic property, confirming that contaminating enzymes do not account for the low activity of the K145Q mutant enzyme. The rates of the forward reaction for both wild-type and mutant enzymes were 30-40 times higher than the rates of the reverse reaction. KM values for the four substrates were 10 to 100 higher for the mutant compared to the wild-type enzyme. Whereas D-alanine is preferred over L-alanine by the wild-type enzyme (10(3) higher kcat/KM for D- over L-alanine), the K145Q enzyme does not efficiently discriminate between L- and D-alanine. Both wild-type and mutant enzymes also catalyze the slow racemization of L- and D-alanine. Proton NMR studies showed that wild-type enzyme catalyzed a time-dependent exchange of the C alpha proton of D-alanine with solvent D2O and a slow exchange of the alpha proton of L-alanine; the latter slow exchange rate is the same for the C alpha proton of both L- and D-alanine with the K145Q mutant enzyme. Thus, in addition to binding pyridoxal 5'-phosphate, the active-site Lys-145 of D-amino acid transaminase is involved in several other important functions, i.e. it optimizes catalytic efficiency and it maintains stereochemical fidelity. The steady-state kinetic results on the K145Q mutant enzyme together with the findings on the relative racemization rates and the NMR protein exchange data suggest that an alternate base catalyzes abstraction of the alpha proton of substrate in this mutant D-amino acid transaminase. PMID- 8463225 TI - A single amino acid substitution confers progesterone 6 beta-hydroxylase activity to rabbit cytochrome P450 2C3. AB - A cDNA encoding a naturally occurring variant of cytochrome P450 (P450) 2C3 that catalyzes the 6 beta- and 16 alpha-hydroxylation of progesterone exhibits six differences of nucleotide sequence leading to five amino acid substitutions from that encoding 2C3, a progesterone 16 alpha-hydroxylase that does not catalyze 6 beta-hydroxylation. Analysis of chimeric and mutant enzymes indicates that a Ser/Thr difference at position 364 underlies the difference between the two enzymes in 6 beta-hydroxylase activity as well as sensitivity to the inhibitor, 16 alpha-methylprogesterone. In addition, an Ile/Met difference at position 178 influences the apparent Km for progesterone. The two mutations, S364T and 1178M, together convert 2C3 to a form that exhibits kinetic properties which are similar to the 2C3v enzyme, and the reciprocal mutations in 2C3v convert it to an enzyme that resembles 2C3. Interestingly, position 364 of 2C3 maps to a substrate contacting domain suggested by models for mammalian P450 enzymes based on the structure of P450cam. Ile178 is highly conserved among mammalian microsomal P450s with the exception of CYP4A and CYP19 enzymes which exhibit a Met at this alignment position. PMID- 8463226 TI - Spontaneous Ca2+ spiking in a vascular smooth muscle cell line is independent of the release of intracellular Ca2+ stores. AB - Monolayers of fura-2-loaded A7r5 cells, a cell line derived from rat embryonic aorta, generated spontaneous Ca2+ spikes that were synchronized within the cell population. These Ca2+ spikes were abolished by removal of extracellular Ca2+ or addition of nimodipine (50 nM), and their frequency was increased by depolarization with high K+ or by treatment with BAYK 8644 (1 microM), indicating that Ca2+ entry through L-type Ca2+ channels is required for Ca2+ spiking. Several lines of evidence indicate that mobilization of intracellular Ca2+ stores is not necessary for this Ca2+ spiking. 1) Ryanodine (0.1-50 microM) neither stimulated Ca2+ mobilization nor affected Ca2+ spiking; 2) the complex effects of caffeine were mimicked by theophylline, 8-bromo-cyclic adenosine 3':5' monophosphate (8-bromo-cAMP), and forskolin, suggesting that the caffeine effects may be mediated by cAMP and not by ryanodine receptors; 3) prolonged incubation with thapsigargin (50 nM), which depletes intracellular Ca2+ stores, did not affect the frequency of Ca2+ spiking; 4) Ba2+ or Sr2+ could substitute for Ca2+ in the spike-generating mechanism even when intracellular stores were depleted of Ca2+. Under conditions where the sarcoplasmic reticulum (SR) contained Ca2+, Ba2+ spikes did not cause Ca2+ mobilization. The mechanisms involved in generating spontaneous Ca2+ spiking in A7r5 cells are therefore likely to reside in the sarcolemma and to operate independently of SR Ca2+ uptake and release. PMID- 8463227 TI - Transcription of photoreceptor genes during fetal retinal development. Evidence for positive and negative regulation. AB - Rod photoreceptor outer segments are elaborated at approximately 6 months gestation in the cow coinciding with a dramatic increase in mRNAs encoding many visual transduction and associated proteins. Nuclear run-on determination of relative transcription rates demonstrates that gene expression follows three distinct patterns. Opsin, S-antigen, and transducin are all minimally detectable at 5.2 months gestation and increase throughout development. Only opsin demonstrates an additional sharp increase in transcriptional activity which resembles a positive gene-specific enhancer that is first effective between 6.3 and 7.4 months gestation. In contrast, interphotoreceptor retinoid binding protein (IRBP) transcription is already at 43% of its adult level at 5.2 months gestation. To further understand these differences, the relative contributions of initiation and elongation to nuclear run-on signals were examined using either Sarkosyl or ammonium sulfate. Transcriptional rates for S-antigen and transducin were not affected, however, opsin was reduced approximately 4-fold and IRBP was increased approximately 2-fold. Opsin is therefore likely to be initiated de novo during the run-on reaction and responds to a gene-specific positive regulator. The increase in IRBP transcription rate suggests the removal of an elongation inhibitory factor and supports the idea that a negative regulatory element may be involved in controlling IRBP expression. PMID- 8463228 TI - Physiologic concentrations of glucose regulate fatty acid synthase activity in HepG2 cells by mediating fatty acid synthase mRNA stability. AB - Carbohydrate feeding of animals results in striking increases in hepatic fatty acid synthesis but much of this induction is presumed to be hormone mediated. To clarify the mechanisms responsible for the specific effect of carbohydrate on fatty acid synthesis, the effects of D-glucose on the expression of human fatty acid synthase (FAS) in HepG2 cells cultured in serum-free medium were studied. Northern blots of total RNA from these cells showed a single FAS mRNA band of 9.3 kilobases that was increased 2.7-5.4-fold in the presence of D-glucose. Lactate and citrate but not L-glucose mimicked this effect. Glucose induction of FAS mRNA was time- and concentration-dependent and most of the increase in FAS message was detected within the range of physiologic glucose concentrations. Glucose induction of FAS mRNA, protein synthetic rate, and enzyme activity were similar suggesting that glucose regulates FAS expression at a pretranslational level in this system. Transcription run-off experiments showed that glucose feeding was associated with no change in the FAS transcription initiation rate despite a 5 fold increase in FAS mRNA. FAS mRNA stability as determined by actinomycin D chase was 7-fold greater in the presence of glucose. Differences between FAS mRNA levels in cells grown in the presence versus the absence of glucose were inhibited by cycloheximide but not puromycin, suggesting that glucose regulation of FAS mRNA stability is not dependent on translation. Glucose, at physiologic concentrations and in the absence of hormones, appears to regulate FAS gene expression in HepG2 cells predominantly by mediating FAS mRNA stability. PMID- 8463229 TI - Oxygenation of (3Z)-nonenal to (2E)-4-hydroxy-2-nonenal in the broad bean (Vicia faba L.). AB - Incubation of (3Z)-nonenal (NON) with the 269,000-g particle fraction of seed homogenate of the broad bean (Vicia faba L.) afforded (2E)-4-hydroxy-2-nonenal (HNE) as the principal product. One pathway of HNE formation consisted of initial oxygenation of NON into (2E)-4-hydroperoxy-2-nonenal (HPNE) by a novel (3Z) alkenal oxygenase activity, followed by conversion of HPNE into HNE by a previously recognized hydroperoxide-dependent epoxygenase. The hydroperoxide intermediate was detected in coincubations of NON and oleic acid, in which experiments the HPNE generated from NON supported epoxygenase-catalyzed epoxidation of oleic acid into 9,10-epoxystearic acid. Furthermore, by using an enzyme preparation in which the epoxygenase had been inactivated by pretreatment with hydrogen peroxide it was possible to isolate and characterize racemic (4R,4S) HPNE following incubation of NON. Although the (3Z)-alkenal oxygenase resembled a lipoxygenase in its action, it was not inhibited by the lipoxygenase inhibitors, 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid. In a second pathway, HNE was produced by rearrangement of 3,4-epoxynonenal, which was in turn formed from NON by a reaction catalyzed by hydroperoxide-dependent epoxygenase. Support for this pathway came from experiments in which 18O-labeled HNE was isolated following coincubation of NON and 13-18O-labeled linoleic acid 13-hydroperoxide. The existence of 3,4-epoxynonenal as a transient intermediate in HNE biosynthesis was further demonstrated by the isolation of 3,4-epoxynonenal (61% (4R)-configuration) as a trapping product in short time incubations interrupted by addition of sodium borohydride. The two pathways established for biosynthesis of HNE involved the hydroperoxide-reducing and the olefin epoxidizing activities of hydroperoxide-dependent epoxygenase. In the absence of extraneous olefins and hydroperoxides the two pathways would be tightly coupled and follow the stoichiometry: 2NON + 1O2-->2HNE. It was also shown that the V. faba particle fraction catalyzed oxygenation of (3Z)-hexenal into (2E)-4-hydroxy 2-hexenal. PMID- 8463230 TI - The cysteine introduced into the alpha subunit of the Escherichia coli F1-ATPase by the mutation alpha R376C is near the alpha-beta subunit interface and close to a noncatalytic nucleotide binding site. AB - Mutation of the alpha subunit of the Escherichia coli F1-ATPase to convert Arg 376 to a Cys (alpha R376C) lowers multisite ATPase activity 400-1,000-fold while affecting unisite catalysis only around 6-fold, suggesting that the mutation is in a region important for transmission of conformational changes between catalytic sites (Soga, S., Noumi, T., Takeyama, M., Maeda, M., and Futai, M. (1989) Arch. Biochem. Biophys. 268, 643-648; this study). To learn more of the structural features of the segment of the alpha subunit around Arg-376, mutant enzyme with a Cys at this position was modified with several maleimides. N [14C]Ethylmaleimide reacted rapidly with this Cys in one of the three alpha subunits/F1 (2,500 M-1 s-1); more slowly with a second alpha subunit (390 M-1 s 1); and the same Cys in the third copy of the alpha subunit was completely unreactive to the reagent, indicating asymmetry of alpha subunits in the ECF1 complex. The photoactivatable cross-linker N-(4-azido-2,3,5,6-tetrafluorobenzyl) 3-maleimidopropionamide++ +, when reacted via its maleimide to alpha Cys-376 of the mutant, covalently linked alpha to beta subunits upon photolysis, indicating that Cys-376 of alpha is close to an interface between the alpha and beta subunits. The EDTA-induced exchangeable noncatalytic site could be filled by TNP ATP in both wild type and alpha R376C mutant ECF1. Occupancy of this site in the alpha R376C mutant altered the rate of reaction of the second-fastest reacting Cys-376 from 390 M-1 s-1 to below 130 M-1 s-1, suggesting that the two sites are on the same alpha subunit. TNP-ATP in the EDTA-induced exchangeable noncatalytic site was quenched by reacting Cys-376 with 4-maleimido-(2,2,6,6 tetramethylpiperidine-N(oxyl), indicating that the region around Cys-376, which is involved in transmission of conformational changes between alpha and beta, and noncatalytic sites are maximally 10-12 A from each other. PMID- 8463231 TI - Characterization of endogenous carrier-mediated taurocholate efflux from Xenopus laevis oocytes. AB - Taurocholate efflux was studied in Xenopus laevis oocytes and is consistent with a carrier-mediated process. This carrier can be competitively inhibited and trans stimulated by glycocholate. Transport is also trans stimulated by taurochenodeoxycholate and S-hexylglutathione, but not taurolithocholate or daunomycin, reflecting a range of specificity including substrates of both the hepatic canalicular bile acid transporter and the multispecific organic anion transporter. In addition, ATP added to the outside of the oocyte results in an increase in the maximal velocity of this transport process. The physiologic function of this endogenous carrier is not known, but it may act as a generalized system for the efflux of potentially toxic organic anions. PMID- 8463232 TI - Lysine 155 in beta-subunit is a catalytic residue of Escherichia coli F1 ATPase. AB - The "homology A" ("glycine-rich" or "P-loop") consensus sequence occurs in the catalytic sites of F1F0 ATP synthase enzymes. The conserved lysine of this motif is beta-subunit Lys-155 in Escherichia coli F1. The role of this lysine in binding and catalysis at the high affinity ATP binding site was studied with the mutants beta K155Q and beta K155E by measuring the rates of ATP binding/release, ATP hydrolysis/synthesis, and Pi release as a function of pH varied from 5.5 to 9.5. In wild type, protonated beta Lys-155 appears to contribute significantly to high affinity binding of ATP, probably through hydrogen bonding to the gamma phosphate. ATP hydrolysis and synthesis were impaired strongly in the mutants, and the reaction equilibrium constant, which was pH-independent in wild type, was highly pH-dependent in beta K155Q and beta K155E. Studies of steady-state ATPase turnover showed that positive catalytic cooperativity was virtually absent and the pH-dependent component of positive catalytic cooperativity was abolished or reversed in the mutants. The data demonstrate that residue beta K155 is a critical catalytic residue in F1 ATPase. PMID- 8463233 TI - The mechanism of autooxidation of myoglobin. AB - Time courses for the autooxidation of native and mutant sperm whale and pig myoglobins were measured at 37 degrees C in the presence of catalase and superoxide dismutase. In sperm whale myoglobin, His64(E7) was replaced with Gln, Gly, Ala, Val, Thr, Leu, and Phe; Val68(E11) was replaced with Ala, Ile, Leu, and Phe; Leu29(B10) was replaced with Ala, Val, and Phe. In pig myoglobin, His64(E7) was replaced with Val; Val68(E11) was replaced with Thr and Ser; Thr67(E10) was replaced with Ala, Val, Glu, and Arg; Lys45(CD3) was replaced with Ser, Glu, His, and Arg. The observed pseudo-first order rate constants varied over 4 orders of magnitude, from 58 h-1 (H64A) to 0.055 h-1 (native) to 0.005 h-1 (L29F) at 37 degrees C, pH 7, in air. The dependences of the observed autooxidation rate constant on oxygen concentration and pH were measured for native and selected mutant myoglobins. In the native proteins and in most mutants still possessing the distal histidine, autooxidation occurs through a combination of two mechanisms. At high [O2], direct dissociation of the neutral superoxide radical (HO2) from oxymyoglobin dominates, and this process is accelerated by decreasing pH. At low [O2], autooxidation occurs by a bimolecular reaction between molecular oxygen and deoxymyoglobin containing a weakly coordinated water molecule. The neutral side chain of the distal histidine (His64) inhibits autooxidation by hydrogen bonding to bound oxygen, preventing both HO2 dissociation and the oxidative bimolecular reaction with deoxymyoglobin. Replacement of His64 by amino acids incapable of hydrogen bonding to the bound ligand markedly increases the rate of autooxidation and causes the superoxide mechanism to predominate. Increasing the polarity of the distal pocket by substitution of Val68 with Ser and Thr accelerates autooxidation, presumably by facilitating protonation of the Fe(II).O2 complex. Increasing the net anionic charge at the protein surface in the vicinity of the heme group also enhances the rate of autooxidation. Decreasing the volume of the distal pocket by replacing small amino acids with larger aliphatic or aromatic residues at positions 68 (E11) and 29 (B10) inhibits autooxidation markedly by decreasing the accessibility of the iron atom to solvent water molecules. PMID- 8463234 TI - CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid binding lectin. AB - The B lymphocyte cell surface receptor CD22 is an adhesion molecule that can mediate binding to several leukocyte subsets. The first CD22 ligand to be identified was the receptor-linked phosphotyrosine phosphatase CD45, but several lines of evidence suggest that CD22 may interact with multiple counter receptors on adjacent lymphocytes. In the present work, we show that in addition to CD45, a soluble CD22-immunoglobulin fusion protein (CD22Rg) recognizes several other distinct lymphocyte sialoglycoproteins. CD22-mediated adhesion is dependent upon the presence of sialic acids on ligands. CD22Rg is observed to bind specifically to a 115-kDa sialoglycoprotein in COS cells transfected with an alpha-2,6 sialyltransferase cDNA, but not in COS cells transfected with unrelated cDNA clones, indicating that at least some CD22-mediated interactions require presentation of sialic acid in an alpha-2,6 linkage by CD22 ligands. In all cases, truncation of the side chain of sialic acids by mild periodate oxidation abolishes recognition by CD22Rg. Direct binding of CD22Rg to lymphoid cells also requires sialic acids and their side chains. Taken together, these observations indicate that CD22 is a sialic acid-binding lectin and may define a novel functional subset of immunoglobulin superfamily adhesion molecules. PMID- 8463235 TI - Natural ligands of the B cell adhesion molecule CD22 beta carry N-linked oligosaccharides with alpha-2,6-linked sialic acids that are required for recognition. AB - CD22 beta is a glycoprotein found on the surface of B cells during restricted stages of development. It is believed to play a role in cell-cell interactions and B cell activation. The accompanying paper (Sgroi, D., Varki, A., Braesch Andersen, S., and Stamenkovic, I. (1993) J. Biol. Chem. 268, 7011-7018) shows that CD22 beta recognizes multiple glycoproteins on the surfaces of T and B cells and that sialylation of these ligands is essential for binding. To identify the structure(s) of the sialylated oligosaccharide(s) recognized by CD22 beta, [3H]glucosamine-labeled glycoproteins were purified from Daudi cells by adsorption onto a CD22 beta recombinant immunoglobulin (CD22 beta Rg) chimera attached to protein A-Sepharose (PAS), and the N-linked oligosaccharides were released by peptide N-glycosidase F. These released oligosaccharides failed to bind to CD22 beta Rg-PAS under the conditions used initially to adsorb the glycoproteins, but their elution from a column of CD22 beta Rg-PAS was significantly retarded. Populations of oligosaccharides with different affinities could be identified by their order of elution. Specific sialidases were used to determine the content of alpha-2,3- and alpha-2,6-linked sialic acid in these different populations and their contribution to binding. Multiantennary oligosaccharides with one alpha-2,6-linked residue bound marginally, and those with two or more bound more tightly. alpha-2,3-Linked sialic acid residues were without effect. Binding did not require divalent cations and was abrogated by mild periodate oxidation of the outer side chain of sialic acid. No marked differences in size or fucose content were found between the populations of high and low affinity oligosaccharides. However, the low affinity population could be partially converted into higher affinity by treatment with beta-galactoside alpha 2,6 sialyltransferase and CMP-sialic acid. Thus, CD22 beta is a mammalian lectin that can recognize specific N-linked oligosaccharide structures containing alpha 2,6-linked sialic acids. PMID- 8463236 TI - Alpha 4/180, a novel form of the integrin alpha 4 subunit. AB - The integrin alpha 4 beta 1 (VLA-4) is a versatile cell-cell and cell extracellular matrix adhesion receptor. The alpha 4 subunit can be expressed on the cell surface in two forms: an intact form (alpha 4/150) and a cleaved form (alpha 4/80,70). Here we have characterized a third form of alpha 4, called alpha 4/180. Although alpha 4/180 (M(r) 180, nonreduced) is different in size than alpha 4/150 (M(r) 150, nonreduced), these two forms are clearly related, as they (i) shared the same amino-terminal sequence, (ii) were both recognized in Western blots by an anti-alpha 4 COOH-terminal antiserum, (iii) migrated with the same apparent size and charge when reduced, and (iv) were both immunoprecipitated using anti-VLA-4 reagents. In pulse-chase experiments, precursors to both forms appeared simultaneously and matured at the same rate, indicating that one is most likely not the biosynthetic precursor of the other. Although reduction of alpha 4/180 to yield alpha 4/150 suggested the release of a cysteine-linked 30-kDa fragment, seven different biochemical techniques failed to identify such a fragment. Also, alpha 4/180 was converted to alpha 4/150 by incubation at pH 11, by treatment with EDTA at 56 degrees C, or by heating in the presence of elevated SDS levels. Together our findings suggest that alpha 4/180 and alpha 4/150 represent different conformations of the same alpha 4 polypeptide, with the former having anomalous slower migration in SDS-polyacrylamide gel electrophoresis. This unusual biochemical feature of alpha 4 is not shared by other beta 1-associated integrin alpha subunits and suggests that VLA-4 has unique structural properties. PMID- 8463237 TI - BLH1 codes for a yeast thiol aminopeptidase, the equivalent of mammalian bleomycin hydrolase. AB - We have cloned the BLH1 gene of the yeast Saccharomyces cerevisiae coding for a peptidase with significant homology to rabbit bleomycin hydrolase. Bleomycin is a glycopeptide antibiotic used for the treatment of human cancers. The antitumor activity of the drug is limited by its metabolic inactivation caused by bleomycin hydrolase, a member of the cysteine protease family. The open reading frame of BLH1 consists of 1,449 base pairs encoding a 55.4-kDa protein consistent with the molecular mass found in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The consensus sequence within the active site region of cysteine proteases is conserved in the yeast enzyme. Biochemical studies on the purified enzyme confirm its classification as a thiol protease. The nonvacuolar enzyme has a molecular mass of 220 kDa, suggesting a homotetrameric structure. It exhibits an aminopeptidase activity with broad substrate specificity. Biochemical and genetic linkage data give evidence that the BLH1 and the LAP3 (Trumbly, R. J., and Bradley, G. (1983) J. Bacteriol. 156, 36-48) encoded aminopeptidases are identical. Deletion of the BLH1 gene is not lethal under normal growth conditions. However, blh1 mutants show hypersensitivity to bleomycin, indicating that bleomycin hydrolase is able to inactivate bleomycin in vivo and to protect cells from bleomycin-induced toxicity. PMID- 8463238 TI - Functional and chemical characterization of Hymenoptaecin, an antibacterial polypeptide that is infection-inducible in the honeybee (Apis mellifera). AB - As part of our ongoing search for novel antimicrobial agents and their use in singular or combined drug therapy, we have isolated a series of polypeptides from the lymph fluid of honeybees. These polypeptides are synthesized de novo, following experimental infection of the insect with live Escherichia coli cells, and confer a broad-spectrum antibacterial defense to the host. We have dissected this humoral "immune" system into its constituent components. In addition to the previously characterized apidaecins and abaecin, we also isolated a member of the defensin family of peptide antibiotics and, now, a novel 93-amino acid long, cationic polypeptide, termed hymenoptaecin. Detailed analysis established the complete chemical structure, including a 2-pyrrolidone-5-carboxylic acid at the N terminus, and indicated major differences with all known antibacterial polypeptides. Under physiological conditions, it inhibits viability of Gram negative and Gram-positive bacteria, including several human pathogens. Lethal effects against E. coli are secondary to sequential permeabilization of outer and inner membrane. In combination, the six-constituent "peptide antibiotics" of bee lymph provide wide-spectrum antibacterial protection in vitro by virtue of complementarity rather than synergism. PMID- 8463239 TI - Effect of myristoylation on GTP-dependent binding of ADP-ribosylation factor to Golgi. AB - ADP-ribosylation factors (ARFs), a family of approximately 20-kDa guanine nucleotide-binding proteins that activate cholera toxin ADP-ribosyltransferase in vitro, have been implicated in intracellular protein trafficking and are thought to cycle between cytosolic and membrane compartments. Although isolated predominantly as soluble proteins, ARFs associate with membranes and phospholipids in a GTP-dependent manner. In contrast to other small GTP-binding proteins, ARFs are NH2 terminally myristoylated. Using a bacterial expression system, recombinant myristoylated and non-myristoylated human ARF5 were produced to investigate the role of myristoylation in its association with Golgi. The recombinant ARFs (myristoylated and non-myristoylated) exhibited similar biochemical activity as measured by GTP binding and in vitro activation of cholera toxin. Myristoylated ARF5, however, demonstrated a temperature- and GTP dependent association with Golgi membranes, whereas non-myristoylated ARF did not bind to Golgi under any of the experimental conditions. These data indicate that myristoylation is necessary, although not sufficient, for membrane attachment, but is not necessary for activation of cholera toxin. PMID- 8463240 TI - The ATP-dependent translocation of phosphatidylserine to the mitochondria is a process that is restricted to the autologous organelle. AB - The general properties of phosphatidylserine synthesis and translocation to the inner mitochondrial membrane which occur in both intact and permeabilized cells are now shown to occur in cells that are disrupted by shearing. In disrupted cells the synthesis of phosphatidylserine requires ATP and is blocked by preventing Ca2+ sequestration. The translocation of nascent phosphatidylserine to the mitochondria also requires ATP in disrupted cells. Using disrupted cells it is possible to test whether the translocation of nascent phosphatidylserine to the mitochondria is restricted to autologous mitochondrial acceptors or is possible with heterologous mitochondrial acceptors. To examine the nature of the transport process, a donor and acceptor population of cells were prepared. The donor cells were poisoned with hydroxylamine which irreversibly inactivates phosphatidylserine decarboxylase and will prevent the conversion of nascent phosphatidylserine to phosphatidylethanolamine. The acceptor cells were not treated with hydroxylamine so that any phosphatidylserine generated in the donor cell that reached the inner mitochondrial membrane of the acceptor cells would be decarboxylated to form phosphatidylethanolamine. Disrupted donor cells were pulse labeled with [3H]serine for 40 min to permit the synthesis of [3H] phosphatidylserine, and then further incorporation of radiolabel was arrested by chelating Ca2+. When the prelabeled disrupted donor cells were mixed with disrupted acceptor cells the latter failed to decarboxylate the nascent phosphatidylserine. In control experiments the addition of hydroxylamine-poisoned cells did not alter the transfer of nascent phosphatidylserine to autologous mitochondria present in unpoisoned cells. These results indicate that the ATP dependent translocation of phosphatidylserine to the mitochondria is a process that is restricted to the autologous organelle. PMID- 8463241 TI - Identification of two subunit A isoforms of the vacuolar H(+)-ATPase in human osteoclastoma. AB - Subunit A is thought to be the main component of the catalytic site of the vacuolar-type H(+)-ATPase. Screening of a cDNA library made from human osteoclastoma tumor tissue revealed the presence of two isoforms of subunit A. HO68 is a cDNA of 3.1 kilobase pairs, corresponding to a mRNA of approximately 3.4 kilobases in osteoclastoma only, encoding a protein of 615 amino acids with a predicted molecular mass of 68177 Da. A second subtype, VA68, corresponding to a mRNA of approximately 4.8 kilobases was present in all tissues analyzed, and codes for a predicted protein of 617 residues and theoretical molecular mass of 68264 Da. These clones share homology with previously published subunit A sequences, and this, together with the tissue distribution of the mRNA, suggests there are ubiquitous (VA68-type) and tissue-specific (HO68-type) isoforms. HO68 shows the closest sequence homology (95% at the amino acid level) to subunit A of a proton-secreting vacuolar-type H(+)-ATPase located in the apical membrane of midgut goblet cells of tobacco hornworm larva (Manduca sexta). We propose that HO68 could correspond to an isoform of subunit A specific for a vacuolar-type H(+)-ATPase located in the osteoclast plasma membrane. PMID- 8463243 TI - A calorimetric study of Ca2+ binding by wheat germ calmodulin. Regulatory steps driven by entropy. AB - A hypothesis has been proposed for Ca(2+)-binding proteins that a regulatory Ca2+ binding step is endothermic and is driven solely by entropy in the absence of Mg2+ (Imaizumi, M., Tanokura, M., and Yamada, K. (1987) J. Biol. Chem. 262, 7963 7966). To confirm this idea, microcalorimetric titrations of wheat germ calmodulin, with Ca2+ in the presence and absence of Mg2+ and with Mg2+ in the absence of Ca2+, have been carried out at 25 degrees C and at pH 7.0. The results indicate that the four binding sites in each molecule are thermodynamically equivalent to one another for both Ca2+ and Mg2+ binding and that the reaction is endothermic for Ca2+ binding in the absence of Mg2+. As compared with bovine brain calmodulin on Ca2+ binding in the absence of Mg2+, Ca2+ binding in both proteins is driven solely by a large favorable entropy change despite unfavorable enthalpy change. Therefore, the above idea seems plausible. PMID- 8463242 TI - Characterization of the mouse carbonic anhydrase II gene promoter. AB - This work characterizes a 250-base pair (bp) fragment of the mouse carbonic anhydrase II (CAII) gene as an efficient but not cell-specific promoter. This fragment contains multiple consensus cis regulatory regions that interact in a complex fashion to regulate transcriptional activity from the promoter. Truncated fragments of the 250-bp promoter retain transcriptional activity. The 90-bp 5' "GC"-rich portion of the promoter can direct transcription independently from the consensus TATA box and also contains a silencer that diminishes transcription from the 3' 160-bp portion of the CAII promoter as well as from the SV40 promoter. There are two nonconsensus dual functioning Ap2-like elements on the promoter that are essential for core promoter activity and cAMP-mediated increases in transcription of the gene. A nuclear protein of approximately 65 kDa binds to these elements and is present in nuclear extracts of nonstimulated and forskolin-stimulated NIH-3T3 cells. I conclude that these nonconsensus Ap2-like elements and their cognitive binding protein play a major role in the expression of the CAII gene. PMID- 8463244 TI - Formation of the stable myosin-ADP-aluminum fluoride and myosin-ADP-beryllium fluoride complexes and their analysis using 19F NMR. AB - The effects of aluminum fluoride and beryllium fluoride on smooth muscle myosin and its subfragments were studied. Mg(2+)-ATPase activity was inhibited in the presence of aluminum fluoride (beryllium fluoride). [3H]ADP bound to heavy meromyosin (HMM) in the presence of aluminum fluoride (beryllium fluoride) and was not dissociated after 3 days of dialysis demonstrating that [3H]ADP was trapped in HMM. These results suggest the formation of a stable HMM-ADP fluoroaluminate (fluoroberyllate) complex. The intrinsic tryptophane fluorescence intensity was increased in the presence of ADP and aluminum fluoride (beryllium fluoride). Acto-S1 was dissociated upon the formation of S1-ADP-fluoroberyllate and actin destabilized S1-ADP-fluoroberyllate complex, while S1-ADP fluoroaluminate failed to bind to actin. Furthermore, when S1 formed the complex with actin, nucleotide trapping did not occur in the presence of fluoraluminate. These results indicated that the myosin-ADP-fluoroberyllate complex resembles a weak binding state while myosin-ADP-fluoroaluminate complex is a distinct conformation although the binding to actin was also weak. The structure of the ternary complex was investigated using 19F NMR. The 19F NMR spectrum of the S1 ADP-fluoroaluminate complex showed a peak at -66.7 ppm which is due to the binding of fluoraluminate to S1. The peak was not observed when 5' adenylylimidodiphosphate was substituted for ADP suggesting that aluminum fluoride plays a role as a phosphate analogue. The stoichiometry of the bound fluoride was determined to be 3.8 mol/mol S1 suggesting that the bound species is AlF-4. PMID- 8463245 TI - Kinetics of structural changes of reconstituted skeletal muscle thin filaments observed by fluorescence resonance energy transfer. AB - Fluorescence resonance energy transfer was measured between probes attached to Troponin-I and actin in the reconstituted skeletal muscle thin filament. Cys-133 on TnI was labeled with 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid, and Lys-61 on actin was labeled with fluorescein 5-isothiocyanate. A large difference in the efficiency of resonance energy transfer was observed between the presence (0.55) and absence (0.76) of Ca2+, which corresponds to the change in the distance of 0.53 nm and is in good accordance with a previous report (Miki, M. (1990) Eur. J. Biochem. 187, 155-162). The fluorescence titration curve of this reconstituted thin filament was measured versus free Ca2+ concentration under physiological conditions in the presence of 8 mM MgCl2. The transfer efficiency changed sharply between pCa 6.9 and 5.75, with a midpoint at pCa 6.25, suggesting that a conformational change of thin filaments occurs with a highly cooperative mode. The time course of this conformational change was followed by measuring the fluorescence intensity change (energy transfer efficiency change) of the labeled reconstituted thin filament after rapid decrease or increase of free Ca2+ concentration with a stopped-flow fluorometer. When the free Ca2+ concentration was increased in the presence of 5 mM MgCl2, the fluorescence intensity increased (the transfer efficiency decreased) with a rate constant of 530 +/- 170 s-1 at 20 degrees C. On the other hand, when the free Ca2+ concentration was decreased, the fluorescence intensity decreased with a rate constant of 43 +/- 5 s-1. The results indicate that the conformational change observed by fluorescence resonance energy transfer corresponds well to the regulation mechanism by troponin-tropomyosin on the reconstituted skeletal muscle thin filament. PMID- 8463246 TI - Molecular characterization of hasB from an operon required for hyaluronic acid synthesis in group A streptococci. Demonstration of UDP-glucose dehydrogenase activity. AB - The membrane-associated hyaluronate synthase produces capsular hyaluronate in group A streptococci by the alternate addition of UDP-N-acetylglucosamine and UDP glucuronic acid. Previous studies identified a locus required for hyaluronate synthase activity and suggested that a gene involved in the production of UDP glucuronic acid (UDP-glucose dehydrogenase) also mapped to the locus. In the present study the putative UDP-glucose dehydrogenase gene (hasB) was cloned and the DNA sequence determined. The hasB gene product was shown to have global similarity with AlgD, a dehydrogenase, which catalyzes the production of GDP mannuronic acid for the alginate capsule of Pseudomonas aeruginosa. Regions of local homology have been identified which apparently correspond to the NAD binding and enzyme active sites of HasB and AlgD. In order to show that hasB expression correlated with UDP-glucose dehydrogenase activity, the hasB gene was cloned under control of the T7 promoter. Hyperexpression of hasB resulted in a protein of approximately 47 kDa and high levels of UDP-glucose dehydrogenase activity were observed. These data demonstrate that hasB encodes the UDP-glucose dehydrogenase of group A streptococci. PMID- 8463247 TI - Interleukin-8 antagonists generated by N-terminal modification. AB - We have previously shown that the residues Glu4-Leu5-Arg6 (ELR) preceding the first cysteine at the N terminus of the 72-residue form of interleukin-8 (IL-8) are essential for receptor binding and neutrophil activation (Clark-Lewis, I., Schumacher, C., Baggiolini, M., and Moser, B. (1991) J. Biol. Chem. 266, 23128 23134). We have now synthesized a series of analogs of IL-8(4-72), the truncated form of IL-8 with the N-terminal sequence ELRC, as potential IL-8 antagonists. Among 26 analogs with deletions or amino acid replacements in the ELR region several inhibited IL-8 function. The most potent were IL-8(6-72), with Arg6 at the N terminus, and IL-8,AAR(7-72) with N-terminal Ala4-Ala5 instead of Glu4 Leu5. They inhibited IL-8 receptor binding, exocytosis (IC50 0.3 microM), as well as chemotaxis and the respiratory burst. Inhibition was restricted to responses elicited by IL-8, GRO alpha, or NAP-2, and no effect was observed when the unrelated agonists fMet-Leu-Phe or C5a were used as stimuli. These results demonstrate that selective antagonists that prevent or attenuate the action of IL 8 and its related chemotactic cytokines are obtained by modification of the ELR sequence at the N terminus. PMID- 8463248 TI - Mass changes of inositol 1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate during cell cycle progression in rat thymocytes. AB - Changes in the cellular mass and the cellular concentration of the highly phosphorylated inositol derivatives inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6) were observed during a complete cell cycle of proliferating rat thymocytes. Inositol polyphosphates were determined by a recently developed anion-exchange HPLC/post-column complexometric dye system (Mayr, G. W. (1988) Biochem. J. 254, 585-591), and data were expressed as mass amounts per cell number or as absolute intracellular concentrations based on cell volume determinations by the cell analyzer system CASY 1. After a very early transient rise in both Ins(1,3,4,5,6)P5 and InsP6 at the beginning of the cell cycle, a decrease of the intracellular concentration of both compounds occurred which then remained on a low level between 24 and 48 h. Between 48 and 72 h the cells divided resulting in a decrease of the cell volume by a factor of approximately 2. During this phase a pronounced increase of Ins(1,3,4,5,6)P5 and InsP6 was observed. These increases were already seen when the data were expressed as mass per cell number, but were even enhanced when expressed as absolute intracellular concentrations. In conclusion, we present as a novel finding long term changes in the intracellular concentrations of Ins(1,3,4,5,6)P5 and InsP6 in proliferating thymocytes. This may indicate a role for these compounds during cell cycle progression. PMID- 8463249 TI - Active baculovirus recombinant p70s6k and p85s6k produced as a function of the infectious response. AB - Rat p70s6k and p85s6k have been expressed in baculovirus recombinants propagated in Sf9 insect cells. Surprisingly, both recombinant isoforms were active without coinfection of other kinases which lie upstream in the signaling pathway. Treatment of either recombinant form with phosphatase 2A leads to immediate inactivation in the absence of phosphatase inhibitors. Further studies show that the same four major Ser/Thr-Pro sites associated with p70s6k activation following mitogenic stimulation in vivo are also the four major sites phosphorylated in both the p70s6k and p85s6k during the infection process. It is proposed that the production of phosphorylated and activated recombinant p70s6k and p85s6k is due to activation of a host cell signaling pathway which is triggered by viral infection. In support of this hypothesis, wild-type virus-, but not mock-infected cells, exhibit the multiple phosphorylation of a ribosomal protein which migrates similar to ribosomal protein S6 on two-dimensional-polyacrylamide gels and extracts from these same cells contain elevated levels of S6 kinase activity. PMID- 8463250 TI - Thrombospondin is a tight-binding competitive inhibitor of neutrophil elastase. AB - Thrombospondin, a glycoprotein of three identical disulfide-bonded subunits, is a constituent of platelet alpha-granules and a variety of normal and transformed cells and binds to cell surfaces and becomes incorporated into extracellular matrix. It has been implicated in processes such as wound healing and tumor growth and metastasis. In addition, thrombospondin was shown recently to be an inhibitor of the fibrinolytic enzyme, plasmin. In the cause of studying the effects of thrombospondin on other serine proteinases, we found that thrombospondin binds neutrophil elastase in an active-site-dependent manner and competitively inhibits the activity of the enzyme. In a competitive binding assay, neutrophil elastase bound to thrombospondin with a dissociation constant of 17 +/- 7 nM, expressed per mole of thrombospondin trimer, or 52 +/- 20 nM, expressed per mole of thrombospondin subunit. In kinetic studies of the inhibition of the amidolytic activity of neutrophil elastase by thrombospondin, 2.7 +/- 0.3 mol of elastase interacted with 1 mol of thrombospondin trimer with a site-binding constant of 57 +/- 13 nM. Lower limits for the on rate constant of 5 x 10(6) M-1 s-1 and off rate constant of 0.27 s-1 were established. Affinity of binding of neutrophil elastase to thrombospondin was sensitive to ionic strength and calcium ions. Thrombospondin was cleaved by neutrophil elastase, but the site(s) of the limited cleavage are independent of the competitive inhibition of elastase activity by thrombospondin. Neutrophil elastase inactivated with phenylmethylsulfonyl fluoride did not compete with active elastase for binding to thrombospondin, implying that a functional active site is important for the interaction of elastase with thrombospondin. Thrombospondin protected fibronectin from cleavage by neutrophil elastase. In summary, the binding of neutrophil elastase to thrombospondin is tight, reversible, and close enough to the active site of elastase to exclude small synthetic tripeptidyl p-nitroanilide substrates and macromolecular protein substrates. Two potential reactive centers that may be involved in binding elastase have been identified in the calcium-binding type 3 domains of thrombospondin. Neutrophil elastase is the enzyme primarily responsible for degrading and solubilizing connective tissue during inflammatory processes. These findings suggest a previously unsuspected mechanism for regulation of elastase activity at inflammatory sites. PMID- 8463251 TI - Replication protein A is the major single-stranded DNA binding protein detected in mammalian cell extracts by gel retardation assays and UV cross-linking of long and short single-stranded DNA molecules. AB - Band shift and UV cross-linking assays were used to analyze the major single stranded DNA (ssDNA) binding activity in lysates of primate and rodent cells. The ssDNA binding activity behaved chromatographically similar to that of replication protein A (RP-A), a multisubunit protein containing three polypeptides of molecular mass 70, 34, and 14 kDa. A 70-kDa protein was found to harbor the ssDNA binding activity when UV cross-linked to long ssDNA or to oligonucleotide probes. Monoclonal antibodies against the 70- and the 34-kDa subunits produced super-gel shift patterns, demonstrating that the reactive protein is indeed RP-A and that the retarded native binding complex included both subunits. RP-A displayed oligonucleotide-specific binding dependent on oligomer length. Increasing oligonucleotide length led to the formation of slow migrating complexes harboring multiple RP-A molecules, suggesting that an interval of about 20-30 bases is required for the binding of RP-A molecules. While similar binding activity was detected in cell extracts derived from proliferating and quiescent cells, a sharp decline in ssDNA binding activity was observed in the SV40-transformed Chinese hamster cell line 631 following UV irradiation. The nature of this decrease in activity and its possible effect on DNA replication is discussed. PMID- 8463252 TI - Vaccinia virus ribonucleotide reductase. Correlation between deoxyribonucleotide supply and demand. AB - Ribonucleotide reductase has been suggested as a rate-limiting enzyme in DNA synthesis, partly because activities of the enzyme in cell-free preparations are low relative to rates needed to sustain DNA replication at observed rates. Vaccinia virus, with a large duplex DNA genome, encodes both subunits of a specific ribonucleoside diphosphate reductase. In this report, we describe quantitative analysis of ribonucleotide reductase protein levels and DNA accumulation in vaccinia virus-infected cell extracts, to correlate the supply of deoxyribonucleotides with the demand for these precursors in viral DNA synthesis. To do this, we generated polyclonal antisera to TrpE fusion proteins constructed from the carboxyl termini of both subunits of viral ribonucleotide reductase. We used S1 nuclease and immunoprecipitation analysis to determine the transcriptional and translational kinetics of vaccinia virus ribonucleotide reductase expression. Enzyme activity and ribonucleotide reductase protein stability were also assayed during the time course of viral infection. Enzyme linked immunoassays were used to quantitate protein levels, and filter hybridizations were used to measure the accumulation of viral DNA. We show that ribonucleotide reductase activity in vaccinia virus-infected cells is severalfold higher than needed to provide deoxyribonucleotides at rates commensurate with DNA synthesis. Thus, while the enzyme is important as catalyst for the first committed reaction in DNA replication, it is not rate-limiting for this process. PMID- 8463253 TI - Contribution of platelet microparticle formation and granule secretion to the transmembrane migration of phosphatidylserine. AB - Activation of human platelets by complement proteins, C5b-9, thrombin plus collagen, or a Ca2+ ionophore results in surface exposure of phosphatidylserine (PS), accompanied by the expression of membrane catalytic activity for the tenase (VIIaIXa) and prothrombinase (VaXa) coagulation enzyme complexes. The mechanism underlying this surface exposure of PS upon platelet activation remains unresolved. Using fluorescent derivatives of PS (NBD-PS), we have investigated how the transmembrane migration of PS is related to microvesiculation of the platelet plasma membrane and to fusion of storage granules with the plasma membrane. Gel-filtered platelets were incubated with NBD-PS, allowing 90 +/- 10% of the incorporated NBD-PS to accumulate into the inner leaflet of the plasma membrane. Migration of NBD-PS from the inner leaflet to the plasma membrane surface was monitored by time-based flow cytometry, and correlated with the appearance of platelet microparticles and alpha-granule secretion. Platelet activation by C5b-9 or the Ca2+ ionophore, A23187, increased surface exposure of NBD-PS, due to acceleration of the apparent rate of migration from inner to outer plasma membrane leaflets. The onset of this accelerated migration of NBD-PS to the surface coincided with the onset of plasma membrane vesiculation, and the NBD PS that partitioned into the membrane of the shed microparticle was also rapidly exposed to the surface (t1/2 < 2 min). In addition to a temporal correlation, microparticle formation and the surface exposure of inner leaflet NBD-PS showed a similar requirement for Ca2+. These results demonstrate that agonist-induced microvesiculation of the platelet plasma membrane is accompanied by accelerated migration of a PS analogue from the inner leaflet to the surface of the shed microparticle membrane, suggesting the mechanism by which induction of platelet microparticle formation exposes catalytic surface for tenase and prothrombinase assembly. PMID- 8463254 TI - Mechanochemistry of the alternatively spliced spectrin-actin binding domain in membrane skeletal protein 4.1. AB - Protein 4.1's interaction with the erythroid skeletal proteins spectrin and actin and its essential role in regulating membrane strength are both attributable to expression of an alternatively spliced 63-nucleotide exon. The corresponding 21 amino acid (21-aa) cassette is within the previously identified spectrin-actin binding domain (10 kDa molecular mass) of erythroid protein 4.1. This cassette is absent, however, in several isoforms that are generated by tissue- and development-specific RNA splicing. Four isoforms of the 10-kDa domain were constructed for comparative assessment of functions particularly relevant to red cells. In vitro translated isoforms containing the 21-aa cassette, denoted 10k21 and 10k19,21, were able to bind spectrin, stabilize spectrin-actin complexes, and associate with red cell membrane. Isoforms replacing or lacking the 21-aa cassette, 10k19 and 10k0, did not function in these assays. A bacterially expressed fusion protein with glutathione-S-transferase, designated GST-10k21, congealed spectrin-actin into a network in vitro as found with purified protein 4.1. Additionally, incorporation of GST-10k21 into mechanically weak, 4.1 deficient membranes increased mechanical strength of these membranes to normal. GST-10k19 did not function in these assays. These results show that the 21-aa sequence in protein 4.1 is critical to mechanical integrity of the red cell membrane. These results also allow the role of protein 4.1 in membrane mechanics to be interpreted primarily in terms of its spectrin-actin binding function. Alternatively expressed sequences within the 10-kDa domain of nonerythroid protein 4.1 are suggested to have different, yet to be defined functions. PMID- 8463255 TI - A polyomavirus enhancer A-binding protein-3 site and Ets-2 protein have a major role in the 12-O-tetradecanoylphorbol-13-acetate response of the human stromelysin gene. AB - The expression of stromelysin, a major matrix metalloproteinase of connective tissues, is regulated by several cytokines, growth factors, protooncogenes as well as by 12-O-tetradecanoylphorbol-13-acetate (TPA). The human stromelysin gene promoter contains an activator protein-1 (Fos/Jun) binding site at -70, which is required for basal expression but is not necessary for the TPA response. In this study, using promoter deletion mutants in transient gene transfection experiments, we first identify the sequence from -220 to -202 as necessary for the TPA response of the stromelysin gene. Further, among the restriction fragments from the 1.3-kilobase long promoter, only the proximal fragment (-274 to -101) conferred a TPA response on the heterologous thymidine kinase gene promoter. The -220 to -202 sequence contains two copies of a motif similar to the polyomavirus enhancer A-binding protein-3 (PEA-3) site, which binds the Ets family of oncoproteins and transcription factors. Point mutations of either one of the two PEA-3 sites, in the 1.3-kilobase long stromelysin promoter context, reduced basal gene expression. However, only the mutation of the proximal, but not the distal PEA-3 site, significantly inhibited the TPA response. In cotransfection experiments, the Ets-2 protein transactivated the stromelysin promoter and the promoter proximal fragment containing the PEA-3 sites but not the promoters containing mutated PEA-3 sites. These data suggest that the PEA-3 site, but not the activator protein-1 site, and Ets-2 protein have a major role in the TPA induction of the human stromelysin gene transcription. PMID- 8463256 TI - The kinetics of formation of complexes between Escherichia coli RNA polymerase and the rrnB P1 and P2 promoters of Bacillus subtilis. Effects of guanosine tetraphosphate on select steps of transcription initiation. AB - The kinetics of formation and dissociation of heparin-resistant transcription initiation complexes between Escherichia coli RNA polymerase and the rrnB P1 and P2 promoters from Bacillus subtilis were investigated using a gel retardation assay. The results suggest that the formation of polymerase-promoter complexes proceeds by a three-step reaction mechanism. The bimolecular collision between free RNA polymerase and the promoter creates a heparin-sensitive complex, which then isomerizes to an initial, and then a subsequent, heparin-resistant complex. We propose that a sequential mechanism best describes the bimolecular collision and that the forward rate constants predominate in the overall rate of heparin resistant complex formation. At 35 degrees C, the association of polymerase with P1 and P2 was very rapid (ka = 1.5 - 2.1 x 10(8) M-1 s-1; kf > or = 0.56 s-1). Direct information on the formation of the closed and intermediate transcription complexes and indirect information on the formation of open complexes suggest that guanosine tetraphosphate did not differentially affect any step between growth rate-regulated and non-growth rate-regulated rRNA promoters by more than 2 fold. PMID- 8463257 TI - Characterization of abnormal free glycophosphatidylinositols accumulating in mutant lymphoma cells of classes B, E, F, and H. AB - Several mutant lymphoma lines are unable to add glycophosphatidylinositol membrane anchors to proteins. Some of them accumulate abnormal glycolipids which can be labeled by tritiated myo-inositol, mannose, or ethanolamine and which are not present in the corresponding parental cell lines. The [3H]myo-inositol labeled abnormal lipids were isolated and characterized using hydrofluoric acid dephosphorylation, nitrous acid deamination, acetolysis, and exoglycosidase treatments alone or in combination. This partial characterization suggests that the class F mutant EL-4-f contains 3 abnormal glycolipids containing 3, 2, or 1 mannose residues, the headgroups of which are Man alpha 1,2Man alpha 1,6(X-->)Man alpha-GlcN-acylinositol, Man alpha 1,6(X-->)Man alpha-GlcN-inositol, and (X- >)Man alpha-GlcN-acylinositol where X represents a charged, hydrofluoric acid sensitive substituent. A fourth, minor abnormal lipid with a Man alpha 1,6(X- >)Man alpha-GlcN-inositol headgroup but a different lipid moiety is also found. The substituent X is likely to consist of phosphoethanolamine since hydrofluoric acid releases [3H]ethanolamine from the [3H]ethanolamine-labeled version of these lipids. Pulse-chase experiments indicate that the abnormal glycophosphatidylinositols of class F mutants are very long-lived. The class B mutant S1A-b has previously been shown to contain an abnormal Man alpha 1,6(phosphoethanolamine-->)Man alpha-GlcN-acylinositol-P-lipid intermediate. Here we show that S1A-b also accumulates a more polar but less abundant lipid which has the identical headgroup structure but lacks the acyl group on the inositol residue. The class E mutant BW5147-e accumulates a hydrophobic glycolipid with the headgroup structure GlcN-acylinositol. All the abnormal glycolipids except those of EL-4-f are heterogeneous with regard to their lipid moiety since base resistant as well as base-sensitive lipids are present. This suggests that the base-resistant alkylglycerols typical of mammalian anchors can get integrated into anchors at early stages of glycophosphatidylinositol formation. PMID- 8463258 TI - Molecular cloning of rat amidophosphoribosyltransferase. AB - The cDNA of rat amidophosphoribosyltransferase (EC 2.4.2.14, ATase), which is the supposed regulatory allosteric enzyme of de novo purine nucleotide biosynthesis, has been cloned by polymerase chain reaction. The predicted open reading frame encodes a protein of 517 amino acids with a deduced molecular weight of 57,436 including a supposed 11-amino acid propeptide. The 16 amino acid residues next to the propeptide were identical to the N-terminal amino acid microsequence of a purified rat liver ATase, which is consistent with the cleavage of the propeptide from the proenzyme in rat liver. The derived amino acid sequence is the first sequence reported for a mammalian ATase and it exhibits 81, 41, 36, and 31% identity with the sequences of chicken, Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae ATases, respectively. The molecular weight (M(r)) of 57,436 suggests a tetrameric structure of native ATase with a M(r) of 240,000 248,000. Southern blot analysis suggested that the ATase gene exists as a single copy in the rat genome. Northern blot analysis revealed that ATase is expressed at a high level in brain, heart, liver, and stomach. The ATase mRNA in brain, heart, and stomach was 3.5 kilobases (kb) and in liver the 3.5-kb band was observed as well as an additional band of 4.2 kb. Reverse transcription polymerase chain reaction analysis showed that ATase is ubiquitously expressed in all tissues examined. Comparison with chicken ATase showed that 2 cysteine residues for an iron-sulfur cluster were conserved. Three conserved and two non conserved consensus phosphorylation sites for cAMP-dependent protein kinase were found. PMID- 8463259 TI - Role of zinc-binding- and hemopexin domain-encoded sequences in the substrate specificity of collagenase and stromelysin-2 as revealed by chimeric proteins. AB - The relationship of enzyme structure to substrate specificity for the matrix metalloproteinases interstitial collagenase and stromelysin-2 has been investigated by analysis of the cleavage specificity of recombinant human collagenase-stromelysin-2 hybrid proteins and C terminally truncated collagenase and stromelysin-2. Two series of chimeric proteins were devised by progressive substitution of exon-encoded domains. The recombinant proteins were expressed in COS-7 cells as protein A-fusion proteins and purified on an IgG affinity matrix. Treatment with 4-amino-phenylmercuric acetate released active metalloproteinase of the sizes predicted for the chimeric proteins. Active forms of both the chimeric protein series and the short form enzymes expressed both casein- and gelatin-degrading activities. Like stromelysin, the catalytic activity of stromelysin-2 was contained in the N-terminal domain (encoded by exons 1-5) and was apparently independent of the C-terminal domain (encoded by exons 6-10). Only full-length collagenase displayed a triple helicase (collagenolytic) activity; no combination of N- or C-terminal collagenase domains fused with stromelysin-2 domains had such activity. This suggests that the triple helicase activity is a composite of elements derived from both halves of the collagenase molecule. C terminally truncated collagenase (exons 1-5) and a hybrid of collagenase exons 1 5 and stromelysin-2 exons 6-10 cleaved denatured type I collagen (gelatin) to generate diagnostic peptides in gelatin fingerprint assays. When exon 5 (the exon encoding the zinc-binding domain) was derived from stromelysin-2, the enzyme specificity in the fingerprint assay changed to that of native stromelysin-2. In contrast, when exon 5 was derived from collagenase, the specificity reflected that of the parent enzyme. Our data also suggest that mismatching of exons 2 and 5 destabilizes the enzyme, presumably by altering the geometry of the propeptide zinc-binding site interaction. We conclude that the loss of triple helicase collagenolytic activity is not accompanied by a shift to the broad specificity characteristic of stromelysin. Rather, the zinc-binding domain confers a distinct cleavage specificity on each metalloproteinase. PMID- 8463260 TI - Mutations within the nucleotide binding site of immunoglobulin-binding protein inhibit ATPase activity and interfere with release of immunoglobulin heavy chain. AB - Immunoglobulin-binding protein (BiP), a 70-kDa heat shock protein in the endoplasmic reticulum, binds transiently to nascent proteins, releasing them upon folding and assembly. The in vitro release of bound proteins from BiP requires ATP hydrolysis. Recently, the three-dimensional structure was solved for an ATP hydrolyzing proteolytic 44-kDa fragment of a 71-kDa heat shock cognate protein, HSC71. Because of the high degree of homology in this region, BiP presumably forms a similar ATP binding structure. Amino-terminal deletions in BiP eliminated ATP-agarose binding. Alteration of a second potential ATP binding site had no effect, suggesting that only the HSC71-like site was capable of ATP binding. Crystallographic data from HSC71 implicated certain amino acids in interactions with the beta-phosphate, gamma-phosphate, and divalent cation of ATP. Mutation of each corresponding residue in BiP (Thr-37, Thr-229, and Glu-201) severely inhibited its ATPase activity. These BiP mutants were still capable of binding ATP and immunoglobulin heavy chains, suggesting that these mutations did not drastically alter the structure of BiP. They did however block the ATP-mediated release of heavy chains from BiP. Our results demonstrate that the structure of BiP in this region must be extremely similar to that elucidated for HSC71 and that mutations of residues proposed to interact with ATP block the ATP-mediated release of bound protein by inhibiting ATP hydrolysis. PMID- 8463261 TI - Immunochemical and biochemical evidence for distinct basement membrane heparan sulfate proteoglycans. AB - Two antigenically and structurally related heparan sulfate proteoglycans (HSPG), with masses of 200 and 350 kDa, have been isolated and characterized from bovine renal tubular basement membranes (BTBM) using DEAE-Sephacel, octyl-Sepharose CL 4B, and Propac PA-1 chromatography. Heparitinase treatment revealed core proteins of 145 and 125 kDa, with corresponding core proteins after trifluoromethanesulfonic acid treatment of 88 and 82 kDa, from the 200- and 350 kDa HSPGs, respectively. The separated HSPGs produced similar tryptic peptide maps, had similar amino acid compositions, and had similarly sized GAG chains. The 200-kDa HSPG had 2.1 mg of protein/mumol of hexuronic acid compared with 1.1 mg/mumol for the 350-kDa HSPG. Anti-BTBM HSPG monoclonal antibody (mAb A12) reacted with core proteins derived from the 200- and 350-kDa HSPGs, whereas anti perlecan polyclonal and monoclonal antibodies did not bind to the BTBM HSPG core proteins described above but reacted with a 230-kDa core protein, which was nonreactive with mAb A12. Immunohistochemical studies of the kidney demonstrated differences in the distribution of BTBM HSPG and perlecan. Comparison of amino acid sequences from BTBM HSPG tryptic peptides with the sequence of perlecan revealed similarities but not extensive identity. Two tryptic peptides show homology to rat agrin, a basement membrane component of synaptic junctions. These data suggest that the two BTBM HSPGs are immunologically and structurally related and that differences in these molecules may arise from alternative splicing or posttranslational modifications. In addition, the two BTBM HSPGs are immunologically and structurally distinct from perlecan but may share homology with agrin. PMID- 8463262 TI - Preferential repression of the H subunit of ferritin by adenovirus E1A in NIH-3T3 mouse fibroblasts. AB - Ferritin is the major intracellular iron-storage protein in eucaryotic cells and plays a prominent role in maintaining intracellular iron homeostasis. We observed that transfection of NIH-3T3 mouse fibroblasts with the adenovirus E1A oncogene specifically repressed the mRNA for one of the subunits of ferritin, ferritin H. This occurred in the absence of any effect of E1A on the mRNA for the L subunit of ferritin. The repression of ferritin H was not a general feature of oncogene expression since transfection of NIH-3T3 cells with H-ras did not affect ferritin composition. Deletion of the conserved regions of E1A responsible for immortalization and transcriptional repression impaired the ability of E1A to repress ferritin H. Immunoprecipitation of ferritin in E1A transfectants demonstrated that the decrease in the ferritin H/L ratio observed at the mRNA level was also exhibited at the protein level. The E1A-dependent inhibition of ferritin H was also observed in a chimeric gene containing the ferritin H promoter ligated to the chloramphenicol acetyltransferase reporter gene, but was not observed in control genes in which chloramphenicol acetyltransferase activity was dependent on promoters derived from SV40 or the interleukin-3 gene. This suggests that E1A may repress ferritin H at the transcriptional level. These results demonstrate that the adenovirus E1A oncogene specifically modulates ferritin H expression. They also suggest that alterations in cellular iron metabolism may be among the diverse array of cellular responses induced by E1A. PMID- 8463263 TI - Isolation and characterization of recombinant human cathepsin E expressed in Chinese hamster ovary cells. AB - The cDNA sequence encoding precursor forms of human cathepsin E (CE), an intracellular aspartic proteinase, was expressed in Chinese hamster ovary cells using an SV40 promotor-driven expression vector. By immunoelectron microscopic studies using an anti-human CE antibody and by Percoll density gradient fractionation, the expressed CE was found to be in two different intracellular fractions; the cytosolic compartment and the vacuolar system. The CEs in both the cytosolic and the vacuolar fractions were highly purified by a simple method involving Percoll density gradient fractionation, chromatography on concanavalin A-Sepharose, Mono Q, and TSK-GelG2000SW, and termed s-CE and v-CE, respectively. The v-CE was further separated into a major (v-CE1) and a minor (v-CE2) form by Mono Q chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed that the s-CE and v-CE1 consists of two polypeptides of 90 and 84 kDa, whereas v-CE2 is composed of 84- and 82-kDa polypeptides. The NH2-terminal amino acid sequence analyses showed that the 90- and 84-kDa proteins from both s-CE and v-CE started with Ser3 and Lys30 of the sequence of human gastric CE predicted from its cDNA sequence, respectively, and that the NH2 terminus of the 82-kDa protein of v-CE2 is the Ile37. Upon acid treatment at pH 3.5 and 37 degrees C for 5 min, the 90- and 84-kDa forms are rapidly converted to the 82-kDa form, indicating that the 90-, 84- and 82-kDa proteins are the pro-CE, the intermediate form, and the mature CE, respectively. All the forms of CE are N glycosylated with high-mannose-type oligosaccharides. The catalytic properties of s-CE and v-CE are comparable to those of natural human CE. These results suggest that the recombinant CE is initially synthesized on membrane-bound ribosomes as a N-glycosylated preproenzyme and that, after cleavage of the signal segment, the 90-kDa proenzyme is proteolytically processed to the intermediate (84 kDa) and mature (82 kDa) forms by the transport system. PMID- 8463264 TI - Importance of the amino terminus of the interleukin-8 receptor in ligand interactions. AB - Interleukin-8 (IL-8) and growth regulatory gene/melanoma growth stimulatory activity (GRO/MGSA) are small polypeptide molecules involved in the chemotactic response of certain cell types. Two receptors have been described which interact with IL-8, designated type 1 and type 2. IL-8 binds with high affinity to both receptors, whereas GRO/MGSA and neutrophil-activating peptide-2 demonstrate a high degree of binding only to the type 2 receptor. The two forms of IL-8 receptor are members of the rhodopsin seven-helix membrane-spanning superfamily, and share a high degree of overall homology, although the amino termini are very divergent. By using conserved restriction enzyme sites, a series of chimeric IL-8 receptor molecules were constructed between the type 1 and type 2 receptors and transfected into human 293 kidney epithelial cells. These chimeric molecules altered regions of the receptor presented to the ligand. The ability of the chimeric receptors to bind IL-8 was determined, as well as the ability of IL-8 and GRO/MGSA to inhibit radiolabeled IL-8 binding. The amino terminus of the IL-8 receptors was found to be important for differential binding of GRO/MGSA and IL 8. In addition, a series of peptides was also constructed to further investigate which residues of IL-8 receptor interact with IL-8. These peptides also identified the amino-terminal sequence of the IL-8 receptors as being important in interacting with IL-8. PMID- 8463265 TI - Toxicity of Bordetella avium beta-cystathionase toward MC3T3-E1 osteogenic cells. AB - Bordetella avium is the etiological agent of an upper respiratory disease in birds which, symptomatically and pathologically, resembles bordetellosis in humans. Studies of the virulence of this organism revealed a novel cytotoxic protein, designated osteotoxin, that was lethal for MC3T3-E1 osteogenic cells, fetal bovine trabecular cells, UMR106-01(BSP) rat osteosarcoma cells, and embryonic bovine tracheal cells. The osteotoxin lacked dermonecrotic toxin activity, exhibited no cross-reactivity with antibody against B. avium dermonecrotic toxin, and was non-proteolytic. Osteotoxin (M(r) approximately 80,000 by gel filtration, pI 5.4) was purified to electrophoretic homogeneity from B. avium 197. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and spectrophotometric analyses showed that the native protein was a homodimer and that each of the non-covalently linked subunits (M(r) approximately 41,000) contained one molecule of pyridoxal 5'-phosphate. Microsequencing of the first 32 amino acids from the NH2 terminus allowed the synthesis of two oligonucleotide probes, which, together with polyclonal antibody to the purified protein, facilitated cloning, sequencing, and expression of the osteotoxin gene product in Escherichia coli. The open reading frame encodes a polypeptide of 396 amino acid residues (M(r) = 42,606, calculated pI 5.9), whose sequence exhibits approximately 38% identity (approximately 60% similarity) to pyridoxal 5' phosphate-dependent beta-cystathionase(s) from E. coli, Salmonella typhimurium, and rat liver. The characteristic motif, TKYXXGHSD, associated with binding the cofactor in these enzymes is also present in osteotoxin. Physicochemical and enzymatic analyses established the coidentity of osteotoxin with beta cystathionase. The region upstream of the beta-cystathionase (metC) gene in B. avium 197 lacked regulatory sequences ("Met boxes") described for metC in enteric species, and enzyme production was not repressed by methionine. Incubation of MC3T3-E1 osteogenic cells in medium containing L-[35S]cystine and purified beta cystathionase resulted in 35S-labeling of the enzyme and at least one major MC3T3 E1 cell protein (M(r) approximately 50,000). cytotoxicity can be attributed to: 1) beta-cystathionase-catalyzed cleavage of L-cystine in the medium and formation of reactive sulfane-containing derivative(s), and 2) transfer of sulfane sulfur to metabolically sensitive or structurally important proteins in the osteogenic cells. PMID- 8463266 TI - The carboxyl terminus of isocitrate lyase is not essential for import into glyoxysomes in an in vitro system. AB - A procedure has been established for the isolation of intact and import-competent glyoxysomes from the cotyledons of sunflower (Helianthus annuus) seedlings. Radiolabeled isocitrate lyase (a glyoxysomal matrix protein) was produced by in vitro transcription of the castor bean cDNA and translation of the RNA in a wheat germ lysate. The heterologous isocitrate lyase was imported into isolated sunflower glyoxysomes and protease-protected. Dihydrofolate reductase, a cytoplasmic protein, neither bound to nor imported into the glyoxysomes. Import of isocitrate lyase was not observed when the glyoxysome fraction was replaced by a mitochondrial fraction. The import of isocitrate lyase into glyoxysomes was temperature- and ATP-dependent. Progressive carboxyl-terminal truncations of the isocitrate lyase gene were transcribed and translated to yield polypeptides with the same amino terminus but lacking varying amounts of the carboxyl terminus. All these polypeptides imported with the same characteristics as the full-length protein, suggesting that targeting information must be present within the first 168 amino acids, and, unlike some other peroxisomal proteins, the carboxyl terminus is dispensable for targeting and import. PMID- 8463267 TI - Bovine stefin C, a new member of the stefin family. AB - Four low M(r) cysteine proteinase inhibitors with different pI values were isolated from bovine thymus using alkaline activation of the gland homogenate, affinity chromatography on carboxymethyl-papain-Sepharose, gel filtration on Sephadex G-50, ion-exchange chromatography on a DEAE-cellulose column and a fast protein liquid chromatography Mono Q column, and hydrophobic chromatography on a TSK Phenyl-5 PW column. One of the inhibitors was identified both as the monomeric and dimeric forms of stefin B. Two others, called cysteine proteinase inhibitor-1 and cysteine proteinase inhibitor-2, were N terminally blocked and most likely belong to the stefin family. The complete amino acid sequence of the last inhibitor, namely bovine stefin C, was determined. The inhibitor consisted of 101 amino acids and its M(r) was calculated to be 11,546. It exhibits considerable sequence homology with other inhibitors from the stefin family. It was identified as the first tryptophane-containing stefin and it had a prolonged N terminus. The four inhibitors had similar inhibitory activities on cysteine proteinases. They were fast-acting inhibitors of papain and cathepsin L (kass > or = 1.8 x 10(6) M-1 s-1) and formed very tight complexes with the enzymes (Ki < or = 180 pM). In contrast, they were relatively poor inhibitors of cathepsin B (Ki > 100 nM). PMID- 8463268 TI - The human low affinity immunoglobulin G Fc receptor IIC gene is a result of an unequal crossover event. AB - We have isolated and characterized three genes coding for hFc gamma RIIA, IIB, and IIC. Each gene spans approximately 15-19 kilobases of DNA and consists of eight exons. Two exons encode the 5'-untranslated region and signal peptides, two exons code for homologous Ig-like extracellular domains, a single exon encodes the transmembrane spanning region, and three exons encode the cytoplasmic domains and 3'-untranslated regions. Analysis of gene structures support the concept that the hFc gamma RIIA and hFc gamma RIIB genes originated via gene duplication and divergence processes. The hFc gamma RIIC gene, however, showed a remarkable homology at its 5' end with the hFc gamma RIIB gene, whereas its 3' region was highly homologous with the hFc gamma RIIA gene, suggesting that the hFc gamma RIIC gene results from an unequal crossover event between the hFc gamma RIIA and IIB genes. This hypothesis was supported by nucleotide sequence analyses of the putative break-point region. The proposed site of recombination was located approximately 300 nucleotides downstream from the sixth (C1) exon. These data provide a unique model for the evolutionary generation of a receptor family with multiple biological functions. PMID- 8463269 TI - Regulation of heme oxygenase and metallothionein gene expression by the heme analogs, cobalt-, and tin-protoporphyrin. AB - Two heme analogs, cobalt- and tin-protoporphyrin (CoPP and SnPP, respectively) have been used to probe the heme-hemopexin interaction, hemopexin receptor binding, and the mechanism of regulation of heme oxygenase (HO) and metallothionein-1 (MT-1) gene expression by hemopexin. Both CoPP and SnPP are HO inhibitors and hemopexin binds SnPP (Morgan, W. T., Alam, J., Deaciuc, V., Muster, P., Tatum, F. M., and Smith, A. (1988) J. Biol. Chem. 263, 8226-8231) and CoPP. The association of CoPP with hemopexin produces characteristic changes in the absorbance spectrum of CoPP and quenches the intrinsic fluorescence of hemopexin. Binding of CoPP is tight (Kd ca. 3 x 10(-7) M) although of lower affinity than heme itself (Kd < pM); and CoPP binding, like heme, produces conformational changes in hemopexin shown by an increase in the molar ellipticity at 233 nm and affords protection from proteolysis of the hinge region between the two structural domains of hemopexin. The coordination of the central cobalt atom is predicted to be similar to that of heme and to involve His56 and His127 of rabbit hemopexin. Furthermore, CoPP-hemopexin, like SnPP-hemopexin, binds to the hemopexin receptor as shown by competitive inhibition studies with radioactive heme-hemopexin. The effect of free heme analogs and their hemopexin complexes on HO and MT gene regulation was investigated and compared with the extent of induction by heme and heme-hemopexin. Free CoPP is a more effective inducer of HO steady state mRNA levels than free heme and produces a 5-fold increase within 1 h compared to only a 2-fold increase with heme, but free SnPP (up to 10 microM) produces no detectable increase in HO mRNA. In contrast, by 3 h heme-hemopexin and SnPP-hemopexin increase HO mRNA levels 11- and 6-fold, respectively; but the CoPP-hemopexin complex causes no detectable change in HO mRNA levels. The complexes of hemopexin with heme or either of the two heme analogs are effective inducers of metallothionein (MT) mRNA. Induction of MT mRNA by heme-hemopexin is rapid, increasing 4-fold within 1 h and 14-fold by 3-4 h. Strikingly, an even more rapid and slightly more extensive induction of MT mRNA is seen in response to either CoPP- or SnPP-hemopexin complexes, with MT mRNA rising 8-fold within 1 h. In contrast, free heme and the free analogs are far less effective inducers, increasing MT and mRNA levels and in vitro transcription rates only 3-4-fold and declining after 2-3 h.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463270 TI - Peptide splicing in the vacuolar ATPase subunit A from Candida tropicalis. AB - Subunit A of the vacuolar proton pump appears to be responsible for the ATP hydrolysis which is coupled to the pumping of protons into a variety of intracellular acid compartments, including the fungal vacuole. We report here the cloning and sequence determination of the gene encoding subunit A from Candida tropicalis. Southern blot hybridization analysis indicates that there is a single gene which encodes this protein. The gene contains a single intron at the extreme 5'-end of the coding region. The gene is predicted to encode a polypeptide of 1088 residues with a calculated molecular mass of 119,019 daltons, yet the mature polypeptide appears to be approximately 67 kDa, indicating that this protein probably undergoes the same sort of processing that is evidenced in the homologous protein from Saccharomyces cerevisiae in which an approximately 50-kDa polypeptide (the spacer) is spliced out of the mature protein. The Candida gene, with and without this middle portion, has been expressed in S. cerevisiae and found to restore a Saccharomyces subunit A deletion mutant (tfp1-delta 8) to apparently wild-type growth at pH 7.6, and normal vacuolar acidification. The peptide sequence of the two predicted mature ends is very similar to the sequences of the analogous proteins from Daucus carota, S. cerevisiae, and Neurospora crassa (60.5, 87.4, and 72.9% identity, respectively), but the middle portion bears only very limited homology with the Saccharomyces protein sequence. Processing of the gene product occurs in S. cerevisiae, Escherichia coli, and in rabbit reticulocyte-mediated in vitro translation, indicating that the excision is probably autocatalytic. The limited sequence identity seen between the Saccharomyces and Candida spacer domains may considerably narrow the functionally important regions responsible for the excision event. PMID- 8463271 TI - Extract-specific heterogeneity in high-order complexes containing apolipoprotein B mRNA editing activity and RNA-binding proteins. AB - The mechanism for tissue-specific differences in apolipoprotein B (apoB) mRNA editing efficiency is not known. Structural data are presented which demonstrate tissue-specific, quantitative differences in the high order complexes containing apoB mRNA editing activity and RNA-binding proteins. The bulk of rat enterocyte extract editing activity sedimented at 11 S with an additional 5-10% at 60 S. Rat liver extract activity was less abundant and only sedimented at 60 S. Ultraviolet light cross-linking revealed two protein activities of approximately 66 and 44 kDa which specifically associated with apoB RNA substrates and cosedimented with editing activity. Extracts differed in the cross-linking yield of p66 and p44 and kinetically, enterocyte RNA-protein complexes reached maximum abundance more rapidly than those in liver extracts. Both 60 and 11 S forms of the editing activity redistributed to 27 S during in vitro editosome assembly. The redistribution of editing activities was accompanied by a corresponding redistribution of p66/p44 to 27 S. The data demonstrate that p66 and p44 are common to liver and enterocyte 27 S editosome assembly processes and suggest that differences in both the pre-editosomal assembly state of editing factors and their abundance may be mechanistically important for tissue-specific differences in editing efficiency. PMID- 8463272 TI - Relationship between alpha subunit ligand occupancy and beta subunit autophosphorylation in insulin/insulin-like growth factor-1 hybrid receptors. AB - Insulin receptor beta subunit autophosphorylation occurs in an intramolecular trans-reaction in which one beta subunit phosphorylates the adjacent beta subunit within an alpha 2 beta 2 holoreceptor complex (Frattali, A. L., Treadway, J. L., and Pessin, J. E. (1992) J. Biol. Chem. 267, 19521-19528). To determine the spatial relationship between alpha subunit occupancy and beta subunit autophosphorylation, the vaccinia virus/bacteriophage T7 transient expression system was used to generate insulin/insulin-like growth factor (IGF)-1 hybrid receptors. The extent of hybrid receptor formation was proportional to the molar ratio of the insulin and IGF-1 receptor expression plasmids used for transfection of cultured fibroblasts. Insulin/IGF-1 hybrid receptors displayed high affinity binding for insulin and IGF-1 similar to that observed for homotypic insulin and IGF-1 receptors, respectively. As expected, insulin poorly competed for 125I-IGF 1 binding to the insulin/IGF-1 hybrid receptors compared with IGF-1. IGF-1, however, competed more efficiently than insulin for 125I-insulin binding, indicating interactions between the alpha subunit binding sites. Furthermore, insulin or IGF-1 stimulated the autophosphorylation of both beta subunits within wild type insulin/IGF-1 hybrid receptors. Ligand-stimulated autophosphorylation of two different mutant/wild type insulin/IGF-1 hybrid receptors also resulted in the labeling of each beta subunit independent of which alpha subunit was occupied with ligand. These data demonstrate that insulin/IGF-1 hybrid receptors bind both ligands with high affinity and that occupancy of either alpha subunit results in a series of intramolecular trans-autophosphorylation reactions between beta subunits. PMID- 8463273 TI - A Ca(2+)-independent protein kinase C from fission yeast. AB - A protein kinase C homologue of Schizosaccharomyces pombe, pkc1+, was isolated from a genomic library by screening with the Saccharomyces cerevisiae PKC1 probe. From its primary sequence and biochemical properties, we conclude that S. pombe pkc1+ encodes a phospholipid-activated Ca(2+)-independent protein kinase, homologous to the delta/epsilon classes of mammalian protein kinase C. Gene disruption experiments show that pkc1+ is not essential for cell viability; however, overexpression of the protein leads to an abnormal cell morphology and a block in cell separation following mitosis suggestive of a role in cell division. In vitro phosphorylation experiments reveal several potential pkc1+ substrates. PMID- 8463274 TI - Synthesis and turnover of photosystem II reaction center polypeptides in cyanobacterial D2 mutants. AB - Several mutations in psbD (coding for the photosystem II reaction protein D2) lead to a loss of the entire photosystem II complex from the thylakoid membrane. For two site-directed D2 mutants, E69V (Glu-69 mutated to Val) and ET-9 (introducing a premature stop codon in psbD), and two psbD deletion mutants, the synthesis and degradation of photosystem II reaction center components were analyzed. In E69V, no D2 or psbC-encoded CP43 was detected upon 5-min pulse labeling or Western blotting, whereas a psbDI/C transcript was present. Either D2 and CP43 are very unstable in this mutant, or the mutation causes an inhibition of translation of the psbDC operon. In E69V, the predominant lifetime of D1 is several minutes, but a small fraction of D1 remains stable in the thylakoid for several hours. In E69V, also a 43-kDa band is detected by D1 antisera. We attribute this band to a D1 cross-linking product possibly involved in D1 degradation. We identified a D1 precursor in E69V and psbDI/C/DII-, two mutants with particularly short D1 lifetimes. A unique feature of the E69V mutant is that destabilization of the photosystem II complex is triggered by a single-site mutation leading to extremely rapid turnover or lack of synthesis of D2. PMID- 8463275 TI - In situ capture of mu-calpain activation in platelets. AB - In situ detection of calpain activation in intact cells has not been possible to date. Here we present the first direct evidence, employing a novel approach, that mu-calpain is rapidly activated at cell membranes in platelets upon a rise in intracellular calcium concentration. Immunoelectron microscopy using antibodies capable of distinguishing between the pre- and postautolysis forms of mu-calpain revealed that treatment of platelets with calcium ionophore causes the preautolysis form of the protease to translocate from cytosol to membranes, where it becomes activated by autolysis. This indicates that proteins associated with membranes serve as primary substrates for calpain in cells. PMID- 8463276 TI - Role of oligosaccharides in the processing and function of human transferrin receptors. Effect of the loss of the three N-glycosyl oligosaccharides individually or together. AB - When the coding sequence for human transferrin receptors was expressed in a Chinese hamster ovary cell line lacking endogenous transferrin receptors, 86-kDa molecules containing three N-glycosidically linked oligosaccharides were synthesized. These rapidly dimerized to form 172-kDa molecules which increased in size to 190 kDa. After site-directed mutagenesis of all three N-glycosylation sites, 80-kDa receptors were synthesized and only a few dimers were formed. 84 kDa monomers were synthesized in the absence of the oligosaccharide attached to Asn727 or Asn317. Dimerization and maturation through the Golgi body of the Asn727 mutant receptors were much slower than the wild type whereas the Asn317 mutant receptors behaved more similarly to the wild type. Lack of the oligosaccharide at Asn251 gave rise to 73-kDa monomers because of proteolytic processing (Hoe, M. H., and Hunt, R. C. (1992) J. Biol. Chem. 267, 4916-4923), but a second mutation at a potential cleavage site allowed the formation of 84 kDa receptors. These also dimerized at a similar rate to wild type receptors. The three-site mutant receptors were degraded in the endoplasmic reticulum but all three 84-kDa single site mutant receptor species migrated to the cell surface. However, receptors lacking the oligosaccharide at Asn727 bound and internalized little transferrin as a result of reduced affinity. PMID- 8463277 TI - A distal heat shock element promotes the rapid response to heat shock of the HSP26 gene in the yeast Saccharomyces cerevisiae. AB - Induction of heat shock genes is mediated by heat shock factor (HSF). Our recent genomic footprinting experiments demonstrate that HSF binds constitutively to perfect and imperfect heat shock elements (HSEs) in the HSP26 gene in yeast. Site directed mutagenesis of the single perfect HSE, previously reported to not be involved in regulating gene expression, significantly reduces the rate of response of the gene to heat shock. However, the same mutation only slightly reduced the rate of accumulation of HSP26 mRNA during heat shock. Genomic footprinting experiments indicate that this lag in response to heat shock is due to the failure of HSF to bind efficiently to the mutated HSE. The rate of response to heat shock of synthetic promoters containing one, two, three, or seven perfect HSEs was similar to that observed for the wild-type HSP26 gene. These results suggest that the rate of response to heat shock is correlated with HSF occupancy of HSEs, rather than the number of HSEs in a promoter. As with the wild-type and mutant HSP26 genes, the rate of accumulation of mRNA from synthetic promoters increased only moderately with an increase in the number of HSEs. These results suggest that as few as two HSE-HSF complexes are sufficient to saturate HSF's target in the basal transcription apparatus. PMID- 8463278 TI - A novel class of murine POU gene predominantly expressed in central nervous system. AB - A mouse gene (referred to as Emb) encoding a novel class of POU domain is described. The Emb POU domain shares only 40-50% homology to that of any other POU proteins. Nonetheless, the Emb POU domain can bind to the octamer sequence like other POU domains. Emb is a single-copy gene, located on the distal region of mouse chromosome 15. It is expressed in embryo throughout post-implantation stages, where the most prominent expression is seen in developing central nervous system. In the adult, it is highly expressed in brain, whereas weaker expression can be detected in other organs such as testis, skeletal muscle, and kidney. The expression in adult brain is most evident in neurons of hypocampus formation. Two types of Emb mRNA are expressed in brain; one type encodes a protein of 301 amino acids residues, whereas the other codes for a protein with two extra amino acids residues added at the amino-terminal end of POU domain. These two mRNA species are generated by alternative splicing by utilizing an unusual splice acceptor site: CCTCCCTCTG/. Emb mRNA expressed in testis, on the other hand, encodes a smaller protein lacking most of the amino-terminal region. PMID- 8463279 TI - Ad4BP regulating steroidogenic P-450 gene is a member of steroid hormone receptor superfamily. AB - Bovine cytochrome P-450(11 beta) gene (CYP11B) has six different cis-acting elements, Ad1, Ad2, Ad3, Ad4, Ad5, and Ad6, in the promoter region. The Ad4 site also exists in the promoter regions of other steroidogenic P-450 genes as well as in CYP11B1. An Ad4-binding protein (Ad4BP) which specifically binds to the Ad4 site was purified from bovine adrenal cortex nuclear extract, and its molecular mass was 53 kDa. A complementary DNA encoding Ad4BP was isolated from a bovine adrenal cortex cDNA library. The cDNA clone contained an open reading frame of 1383 base pairs encoding 461 amino acids, whose calculated molecular weight was 51,020. The predicted amino acid sequence of Ad4BP revealed that the protein has a zinc finger domain and a ligand binding/dimerization domain. Ad4BP is a novel member of the steroid hormone receptor superfamily. Comparison of the primary structures of the hormone receptor superfamily showed that Ad4BP was highly homologous to FTZ-F1, which regulates the fushi tarazu gene, and ELP, which is expressed in the murine embryonal carcinoma cells. Transfection of a Ad4BP expression plasmid into CV-1 cells activated the transcription of the CAT reporter gene carrying the Ad4 sequence in the promoter region. PMID- 8463280 TI - Secreted LasA of Pseudomonas aeruginosa is a staphylolytic protease. AB - Full expression of the elastolytic phenotype of Pseudomonas aeruginosa depends on LasA, an extracellular protease with restricted specificity whose mode of action on elastin and biological role is not understood. LasA exhibits amino acid sequence homology to some bacteriolytic proteases and shares several physicochemical properties with the staphylolytic protease of P. aeruginosa. This led us to examine whether the two proteases are the same. Production of LasA and staphylolytic protease by prototrophic and lasA mutant strains of P. aeruginosa was investigated. The two prototrophic strains examined, PAO1 and FRD2, exhibited extracellular staphylolytic activity and secreted LasA. LasA mutants, PAO-E64 lasA1 (Ts), FRD2128 delta lasA, and FRD244 lasA::mTn10, did not exhibit staphylolytic activity. A low level of the LasA protein was detected in the culture filtrate of the temperature-sensitive lasA mutant PAO-E64, but none was detectable in those of the deletion and insertion mutants, FRD2128, and FRD244, respectively. The staphylolytic protease was purified from the culture filtrate of P. aeruginosa strain FRD2 by DEAE-cellulose chromatography. The purified enzyme hydrolyzed pentaglycine into the respective di- and tripeptides and reacted specifically with antibodies against a synthetic peptide identical in sequence to positions 77-98 in LasA. The amino-terminal sequence of the first 15 amino acid residues of the staphylolytic protease was found to be identical with that of the secreted LasA. These results clearly indicate that LasA is a staphylolytic protease. In addition to lysing staphylococci, it may enhance elastolysis by cleaving Gly-Gly bonds, which are abundant in elastin. PMID- 8463281 TI - Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast. AB - Functional complementation of the Saccharomyces cerevisiae glycogen branching enzyme deficiency was screened to isolate human cDNAs that encode this enzyme. Human hepatoma cell line HepG2-derived cDNA libraries using the pAB23BXN yeast expression vector yielded four cDNAs capable of complementing the glc3::TRP1 glycogen branching enzyme mutation. Complementation was recognized by an altered iodine-staining trait. This illustrates that interspecies complementation can be used to isolate rare plasmids from libraries by screening if there is sufficient resolution. The human and yeast glycogen branching enzymes have a 67% identical amino acid sequence over a major portion of their length. The human gene is on chromosome 3. PMID- 8463282 TI - SecY, an integral subunit of the bacterial preprotein translocase, is encoded by a plastid genome. AB - Although the paradigm for the acquisition of photosynthetic organelles is the endocytosis of cyanobacteria-like progenitors by heterotrophic protists, details of this evolutionary process are unclear. The small organellar chromosomes are remnants of the larger bacterial genomes with most genes from the endosymbiont's DNA having been either relocated to the protist's nucleus or entirely lost. As a result of those gene transfers, differences exist between plastids from different algal phyla and higher plants. We report here on the retention of a secY gene in cyanelle (= plastid) DNA of the eukaryotic protist Cyanophora paradoxa. This cyanelle secY encodes a functional protein homologous to SecY of Escherichia coli, identified as a subunit of the preprotein translocase complex. Similarity of the cyanelle and E. coli SecY topology, predicted from sequence information, has been confirmed experimentally through SecY-PhoA fusion protein analysis in E. coli. Cyanelle SecY, expressed in an E. coli secY mutant, substituted for the defective prokaryotic SecY. A plastid-encoded gene for a membrane protein functioning in protein transport across plastid membranes is unprecedented in higher plants. From these results we infer that a functional homolog of the prokaryotic preprotein translocation machinery is retained in some plastids. PMID- 8463283 TI - Mutational analysis of the cAMP-dependent protein kinase-mediated phosphorylation site of Rap1b. AB - Rap1b, a member of the Ras superfamily of low molecular weight GTP-binding proteins, can be phosphorylated by cAMP-dependent protein kinase (protein kinase A). The experiments presented here were undertaken to determine the precise site of this phosphorylation. Because the Rap1 proteins are highly homologous, there are no specific antibodies able to discriminate between them. To overcome this problem, we used a transient expression system of a fused protein containing in the NH2 terminus an epitope for a known antibody. Using this system, the transfected protein was expressed at a high level and was localized in a perinuclear structure, as previously reported for the endogenous Rap1 proteins. The mutational analysis of Rap1b revealed Ser179 as the residue involved in the protein kinase A-mediated phosphorylation. The presence of a Lys179 instead of the wild-type Ser179 (resembling the Rap1a sequence) rendered Ser180 a better substrate for phosphorylation caused by protein kinase A. The mobility shift of Rap1b in SDS gels, observed in cells that were stimulated with agonists that increase cAMP, was caused, at least in part, by the phosphorylation of Rap1b. PMID- 8463284 TI - Identification of protein kinase C (PKC) phosphorylation sites on human lamin B. Potential role of PKC in nuclear lamina structural dynamics. AB - Protein kinase C (PKC) is activated at the nuclear membrane in response to a variety of mitogenic stimuli. In human leukemic cells, the beta II PKC isotype is selectively translocated and activated at the nucleus. We recently identified the nuclear envelope component lamin B1 as a major substrate for nuclear PKC both in whole cells and in vitro. Using highly purified human beta II PKC and isolated nuclear envelopes from the human promyelocytic (HL60) leukemia cell line, we have now determined the major sites for beta II PKC-mediated lamin B phosphorylation. Using a combination of cyanogen bromide cleavage, direct microsequencing, tryptic phosphopeptide, and phosphate release analyses, two major sites of PKC-mediated phosphorylation, Ser395 and Ser405, have been identified. These sites lie within the carboxyl-terminal domain of lamin B immediately adjacent to the central alpha helical rod domain. Functionally, beta II PKC-mediated phosphorylation of these sites leads to the time-dependent solubilization of lamin B indicative of mitotic nuclear envelope breakdown in vitro. beta II PKC-mediated lamin B phosphorylation is inhibited by 1) a monoclonal antibody directed against the active site of PKC, 2) a PKC pseudosubstrate inhibitor peptide, and 3) a PKC peptide substrate. Two observations indicate that PKC-mediated lamin B phosphorylation and solubilization is due to direct phosphorylation of lamin B by PKC rather than indirect activation of a cdc2 kinase. Neither immunodepletion with p13suc1 Sepharose beads nor the presence of a p34cdc2 kinase peptide substrate had any effect on PKC-mediated lamin B phosphorylation. Therefore, we conclude that beta II PKC represents a physiologically relevant lamin kinase that can directly modulate nuclear lamina structure in vitro. Nuclear beta II PKC, like p34cdc2 kinase, may function to regulate nuclear lamina structural stability during cell cycle. PMID- 8463285 TI - Critical residues involved in FMN binding and catalytic activity in cytochrome P450BM-3. AB - Cytochrome P450BM-3 from Bacillus megaterium is a soluble, catalytically self sufficient fatty acid mono-oxygenase that, in structural organization and amino acid sequence, resembles the Class II (microsomal) P450 systems. Its single polypeptide chain contains both a P450 heme domain and an NADPH:P450 reductase domain, each of which bears significant homology with its microsomal counterparts. We report here the critical nature of three amino acids in the reductase domain of this enzyme with respect to FMN binding and catalytic activity. We used site-directed mutagenesis to change glycine 570 to bulkier amino acids; none of these mutant enzymes contained FMN after purification. We also made substitutions for tryptophan 574 and tyrosine 536, which by sequence analogy (Porter, T. D. (1991) Trends Biochem. Sci. 16, 154-158) were proposed to bind FMN through stacking of the aromatic rings with the isoalloxazine ring of the flavin. Mutants of tryptophan 574 which retained the aromatic side chain contained no less than 0.85 mol of FMN per mol of enzyme, while aspartate and glycine substitutions yielded enzymes which did not incorporate FMN. Substitution of tyrosine 536 with aspartate gave an enzyme which contained 0.44 mol of FMN per mol of enzyme but was inactive as a fatty acid hydroxylase and had only 2% of wild-type cytochrome c reductase activity, while the glycine mutant at this position bound no FMN. Furthermore, although all of the mutant enzymes contained 1 mol of FAD per mol of enzyme, the Y536D mutant and those entirely lacking FMN retained no more than 40% of wild-type ferricyanide reductase activity. By assaying these enzymes in the presence of added FMN, we were able to assess the relative importance of the residues in the wild-type sequence with respect to their contribution to FMN binding. In addition, the aromatic mutants of tryptophan 574, which were nearly as active in cytochrome c reduction as wild type P450BM-3, were only 20% as active in myristate hydroxylation as the wild type enzyme, suggesting that this amino acid plays an important role in the flow of electrons between the P450 heme and reductase domains. PMID- 8463286 TI - High affinity binding, endocytosis, and degradation of conformationally modified albumins. Potential role of gp30 and gp18 as novel scavenger receptors. AB - Scavenger receptors interact with a variety of modified proteins, mediate their endocytosis and degradation, and may play an important role in protein catabolism and pathogenic processes such as atherosclerosis, aging, and diabetes. Many scavenger receptors have been detected kinetically but few such binding proteins have actually been identified. Recently, we found that two membrane-associated proteins, gp30 and gp18, interact more avidly with albumins conformationally modified by chemical means or by surface adsorption to colloidal gold particles than with native albumin. In this study, we show that gp30 and gp18 behave similarly to other known scavenger receptors. Competition studies indicate a similar ligand binding profile to other known scavenger receptors. Polyanionic molecules (dextran sulfate, fucoidan, polyglutamic acid, polyinosinic acid, heparin) and modified albumins such as formaldehyde-treated or maleylated albumin (Mal-bovine serum albumin) competed with albumin conjugated to colloidal gold particles (A-Au) for the blotting of gp30 and gp18. A-Au and Mal-bovine serum albumin bound cultured endothelial cells with high affinity. Modified and native albumins were each internalized, but only modified albumins were then released degraded. Inhibition studies revealed that only the same molecules that were effective in blocking A-Au blotting of gp30 and gp18, also inhibited A-Au degradation. Addition of the lysosomotropic agent chloroquine resulted in more than 70% inhibition of degradation. Differential processing of A-Au by cultured smooth muscle and endothelial cells along with fibroblasts was observed in a manner consistent with gp30 and gp18 expression. Cumulatively, these results suggest that gp30 and gp18 may mediate the high affinity binding, endocytosis, and degradation of conformationally modified albumins but not native albumin. PMID- 8463287 TI - Interaction of the human insulin receptor tyrosine kinase from the baculovirus expression system with protein kinase C in a cell-free system. AB - The cytoplasmic domain of the human insulin receptor (HIR) from the baculovirus expression system (BIRK) is a soluble, constitutively activated protein-tyrosine kinase. In a cell-free system, BIRK is phosphorylated on serine and threonine residues by protein kinase C (PKC) purified from rat brain. Two-dimensional tryptic phosphopeptide mapping of PKC-phosphorylated BIRK identified one phosphothreonine and three phosphoserine peptides, which were also in tryptic digests of insulin receptors from insulin- or PMA-treated Chinese hamster ovary (CHO) cells transfected with the HIR. After Lys-C proteolysis of PKC phosphorylated BIRK, radioactive phosphopeptides were purified on a C8 reverse phase high pressure liquid chromatography column. Amino acid sequence analysis identified a phosphothreonine peptide corresponding to amino acids 1331-1340 of the HIR. This peptide contains only one threonine, amino acid 1336, which is identified as a site for PKC phosphorylation in BIRK. CHO cells transfected with the wild type (CHO/HIR) or a mutant human insulin receptor (CHO/HIRT1336N), in which threonine 1336 was substituted with asparagine, were 32P labeled and then stimulated with insulin or phorbol 12-myristate 13-acetate (PMA). Two-dimensional phosphopeptide analysis of the HIR revealed that phosphorylation of phosphothreonine peptide T, shown to be in PKC-phosphorylated BIRK, was increased by insulin or PMA. However, the corresponding peptide was not in the mutant receptor. Therefore, the present study directly identifies threonine 1336 in the HIR as a phosphorylation site for insulin and PMA. These data also show that BIRK can be used as a model for the study of the regulation of the insulin receptor kinase. PMID- 8463288 TI - Propeptide processing during factor IX biosynthesis. Effect of point mutations adjacent to the propeptide cleavage site. AB - Factor IX is synthesized in a precursor form with a propeptide that contains the gamma-carboxylation recognition site, an element which directs the post translational gamma-carboxylation of adjacent glutamic acid residues. After protein synthesis, the propeptide is cleaved to yield the mature Factor IX. To study propeptide processing, anti-proFactor IX antibodies were prepared using a synthetic peptide based upon the sequence of the Factor IX propeptide. Immunoaffinity-purified anti-proFactor IX antibodies were reactive with Factor IX Cambridge, a mutant form of Factor IX containing the propeptide, but were not reactive with Factor IX. These antibodies were used to examine the proteolytic processing of forms of Factor IX containing point mutations at P6, P3, P2, P1, P1', P2', and P3' adjacent to the propeptide cleavage site in order to determine the requirement of each of these amino acids for propeptide cleavage. Furthermore, the hierarchy of different pairs of basic residues at positions P1 and P2 was analyzed. The mutated cDNA constructs were expressed in Chinese hamster ovary cells. Propeptide processing was examined using intrinsically labeled Factor IX immunoprecipitated with either anti-pro-Factor IX antibodies or anti-Factor IX:total antibodies, and the Factor IX species were separated by SDS gel electrophoresis. Under the expression conditions employed, the propeptide of wild type Factor IX was almost completely removed, whereas Factor IX mutated to threonine at P1 was not cleaved. The percentage of propeptide cleaved varied with the amino acid sequences of residues P2 and P1, respectively: Lys-Arg (93%), Arg Arg (66%), Thr-Arg (33%), Arg-Lys (19%), Lys-Lys (10%), and Lys-Thr (< 1%). Apart from alterations of basic amino acids at P1 and P2, nonconservative mutations at P6 and P3 decreased propeptide cleavage, whereas conservative mutations at P3, P1', P2', or P3' resulted in cleavage efficiencies approximately equal to that for wild type Factor IX. These results indicate that the preference of paired basic residues at P1 and P2 is similar to other endopeptidases active toward proteins secreted through the constitutive pathway and that the propeptide residues NH2-terminal to these paired basic residues are important in defining enzyme-substrate binding. PMID- 8463289 TI - An NH2-terminal peptide from the vaccinia virus L1R protein directs the myristylation and virion envelope localization of a heterologous fusion protein. AB - The vaccinia virus L1R gene product is a late protein destined for insertion into the envelope of intracellular virus particles. Because this protein is co translationally modified by the addition of myristic acid to the penultimate NH2 terminal glycine residue, it was of interest to identify the modification signal within the L1R protein and to assess the relevance of myristylation to protein localization. To this end, a family of chimeric reporter genes containing 0-13 codons from the NH2 terminus of the L1R open reading frame fused in-frame to the bacterial chloramphenicol acetyltransferase gene was constructed. The encoded proteins were tested as myristylation substrates in cell-free extracts and infected cells. The results obtained in vitro and in vivo were similar and suggested that although the NH2-terminal 5 amino acids of the L1R protein were the minimum signal required to observe modification by myristate, 12 amino acids were required to obtain wild type levels of myristylation with a modulating role played by the intervening amino acid residues. Furthermore, subcellular fractionation of infected cells expressing the fusion proteins indicated that the NH2 terminus of the L1R protein was capable of targeting the fusion proteins to membrane-containing fractions only if myristylated. In particular, the myristylated fusion protein containing the first 12 amino acids of the L1R protein abutted to the chloramphenicol acetyltransferase protein was found associated with the envelope of intracellular vaccinia virus particles. PMID- 8463290 TI - Binding of Ku protein to DNA. Measurement of affinity for ends and demonstration of binding to nicks. AB - Ku, also known as nuclear Factor IV, is an abundant nuclear DNA-binding protein which requires free DNA ends for the initial interaction with double-stranded DNA (dsDNA) and can bind at multiple sites along dsDNA in an energy-independent manner. Its function in vivo is unknown, but it has been implicated in both DNA replication and repair and in transcriptional control. We have used an electrophoretic mobility shift assay to further define the DNA binding properties of the Ku protein. Titration of Ku to a fixed amount of any of several target linear dsDNA fragments produced ladders of shifted bands proportional to the length of DNA, confirming the multiple binding activity of Ku and demonstrating its sequence-independent nature. Using a short DNA fragment with one Ku binding site, the binding constant of Ku for dsDNA ends was calculated to be 2.4 x 10(9) M-1. Competitive inhibition experiments confirmed the requirement of a free DNA end for binding by Ku and demonstrated that Ku binds isolated nicks in dsDNA. Nick binding was also observed directly using radiolabeled singly nicked circular DNA. The relative affinities of Ku for specific nick sites and free DNA ends were approximately equal, and nick binding was sequence-independent. Finally, in a study of a possible role for Ku in protecting or repairing damaged DNA, Ku was shown to inhibit the ability of T4 DNA ligase to circularize linear dsDNA molecules, demonstrating that some Ku molecules remain at the DNA terminus rather than translocate. A similar inhibition was not observed at nicks. These experiments document a new DNA binding specificity for Ku and further suggest that the high affinity end and nick binding activity is biologically relevant to its functions in vivo. PMID- 8463291 TI - Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo. AB - The ras oncogene product, Ras, is synthesized in vivo as a precursor protein that requires post-translational processing to become biologically active and to be capable of transforming mammalian cells. Farnesylation appears to be a critical modification of Ras, and thus inhibitors of the farnesyl-protein transferase (FPTase) that catalyzes this reaction may block ras-dependent tumorigenesis. Three structural classes of FPTase inhibitors were identified: (alpha hydroxyfarnesyl)phosphonic acid, chaetomellic acids, and zaragozic acids. By comparison, these compounds were weaker inhibitors of geranylgeranyl-protein transferases. Each of these inhibitors was competitive with respect to farnesyl diphosphate in the FPTase reaction. All compounds were assayed for inhibition of Ras processing in Ha-ras-transformed NIH3T3 fibroblasts. Ras processing was inhibited by 1 microM (alpha-hydroxyfarnesyl)phosphonic acid. Neither chaetomellic acid nor zaragozic acid were active in this assay. These results are the first demonstration that a small organic chemical selected for inhibition of FPTase can inhibit Ras processing in vivo. PMID- 8463292 TI - Expression of a kinase anchor protein 75 depletes type II cAMP-dependent protein kinases from the cytoplasm and sequesters the kinases in a particulate pool. AB - A kinase anchor proteins (AKAPs) have a C-terminal binding site for the regulatory subunit (RII beta) of cAMP-dependent protein kinase II beta (PKAII beta) and an N-terminal domain that mediates the targeting and attachment of the anchor protein to intracellular structures. In vitro biochemical studies and recent in situ immunocytochemical analysis (Glantz, S. B., Amat, J. A., and Rubin, C. S. (1992) Mol. Biol. Cell 3, 1215-1228) suggest that AKAPs anchor PKAII beta at specific sites in the dendritic cytoskeleton of neurons. This arrangement would place PKAII beta in proximity with its substrates and create "target sites" for cAMP actions. The foregoing model predicts that (a) RII subunits are freely accessible to AKAPs, (b) PKAII holoenzymes, as well as RII subunits, are anchored, and (c) changes in the level of AKAP can alter the intracellular distribution of type II PKAs. We have addressed these previously untested propositions by overexpressing bovine AKAP75 in a human cell line (HEK293). Non transfected cells express a low level of endogenous AKAP79, and approximately 90% of RII alpha and RII beta subunits are isolated in the cell cytosol. In contrast, stably transfected cells, which express a 10-fold excess of AKAP75, sequester > 90% of their RII subunits in a particulate pool. Catalytic subunits are also transferred to this pool. AKAP75 accumulates in a cell compartment with biochemical properties characteristic of cytoskeleton. Thus, AKAPs have access to and avidly bind cytoplasmic type II PKAs. Moreover, an increase in AKAP content can alter the particulate/cytoplasmic distribution of PKAII beta and PKAII alpha. PMID- 8463293 TI - Transepithelial glycylsarcosine transport in intestinal Caco-2 cells mediated by expression of H(+)-coupled carriers at both apical and basal membranes. AB - Glycylsarcosine (Gly-Sar) transport in human intestinal epithelial (Caco-2) cells has been investigated. Gly-Sar transport, from apical to basal surfaces (Ja-b), and intracellular accumulation are greatest when the apical medium is acidified (apical pH 6.0, basal pH 7.4). Both transport and accumulation are susceptible to saturation and competition. Similarly, Gly-Sar transport, from basal to apical surfaces (Jb-a), is increased with acidification of the basal medium (basal pH 6.0, apical pH 7.4). Apical addition of 20 mM Gly-Sar (pH 6.0) to Caco-2 cell monolayers loaded with the pH indicator BCECF (2',7'-bis(2-carboxyethyl)-5-(6) carboxyfluorescein) caused a marked cytosolic acidification. Basolateral application of 20 mM Gly-Sar (pH 6.0) also caused a fall in intracellular pH. These observations are consistent with the expression of H(+)-coupled dipeptide transporters at both membrane faces of the human intestinal epithelial Caco-2 cell line. We also provide direct evidence for dipeptide-stimulated H(+)-influx, across both apical and basolateral membranes, in this intact epithelial cell system. PMID- 8463294 TI - Pyridoxal 5'-phosphate binds specifically to soluble CD4 protein, the HIV-1 receptor. Implications for AIDS therapy. AB - Considerable effort is being made to design anti-viral drugs for the human immunodeficiency virus type 1 (HIV-1) infection process. Some of this work has focused on CD4 protein, the HIV-1 receptor on T helper lymphocytes. One drug that binds to CD4 protein and inhibits both viral infection and growth is DIDS (4,4' diisothiocyanato-2,2'-stilbenedisulfonate). DIDS is best known for its ability to inhibit erythrocyte band 3 anion exchange. Although the antiviral potency of DIDS is evident in vitro (IC50 approximately 30 microM), intravenous administration of DIDS should not be effective owing to the large number of band 3 molecules present on the red blood cell membrane (approximately 10(6)/cell), and to the very small Kd for DIDS binding to band 3 (approximately 30 nM). Therefore, we sought to identify other anion transport inhibitors that would bind weakly to band 3, but tightly to CD4 protein, and that could be administered to humans without significant toxic side effects. On the basis of our previous work with band 3 (Salhany, J. M., Rauenbuehler, P. B., and Sloan, R. L. (1987) J. Biol. Chem. 262, 15965-15973), we elected to study the binding of pyridoxal 5' phosphate (PLP) to soluble CD4 protein. We have discovered that PLP binds surprisingly tightly to soluble CD4 protein (Kd = 45 microM), with a stoichiometry of about 1 mol of PLP/mol of protein. Furthermore, PLP binding was found to be competitive with DIDS for its binding site on soluble CD4 protein. These results suggest that PLP may be an effective anti-viral agent for the HIV-1 infection process. PMID- 8463295 TI - Utilization of exogenously supplied sphingosine analogues for sphingolipid biosynthesis in Chinese hamster ovary and mouse LM cell fibroblasts. AB - Growth of Chinese hamster ovary and LM cells is inhibited by relatively low concentrations of sphingosine in the culture media. This effect is diminished by an order of magnitude by conversion of this positively charged long-chain amino alcohol to a number of N-acetylated analogues, such as N-acetylsphingosine, N acetylsphingosine phosphate, and N-acetylsphingosine phosphorylcholine. Synthesis of sphinganine and its incorporation into ceramide, sphingomyelin, and glycosphingolipids (GSL) was monitored using a short pulse of [14C]serine together with a long pulse of [3H]-galactose. Compared to unsupplemented cultures, growth with 15-30 microM N-acetylsphingosine suppressed incorporation of 14C radioactivity into ceramide, sphingomyelin, and GSL by 75-95% without accumulation of labeled sphinganine and without any appreciable change in membrane phospholipid or total GSL content. Furthermore, when cells were cultivated with 15 microM [4,5-3H]N-acetylsphinganine to monitor its utilization for sphingolipid synthesis, considerable loss of radiolabel occurred due to desaturation of sphinganine to sphingosine. Nevertheless, most of the residual label was found in the long-chain base and not the acyl group of sphingomyelin, indicating that the exogenously supplied base was utilized intact for complex lipid synthesis. Radiolabel was also found in ceramide and glycosphingolipid fractions. Thus, established cell lines whose growth is very sensitive to long chain amino alcohols can be cultivated with sphinganine (sphingosine) analogues at concentrations which suppress endogenous sphinganine production but support continued synthesis of complex sphingolipids. PMID- 8463296 TI - Primary structure of the gene for glycyl-tRNA synthetase from Bombyx mori. AB - The primary structure of the gene encoding Bombyx mori glycyl-tRNA synthetase was determined by sequence analysis of one cDNA and two genomic clones. The sequence of the protein deduced from the nucleotide sequence was verified by sequence analysis of eight peptides. The M(r) 77,667 protein is encoded in a single open reading frame of 2061 nucleotides. There are no introns in the gene. The deduced protein sequence has no obvious similarity to Escherichia coli glycyl-tRNA synthetase but contains a sequence in its amino terminus that is similar to a sequence found in the Drosophila melanogaster and human glutamyl-tRNA synthetases, the hamster and human histidyl-tRNA synthetases, bovine tryptophanyl tRNA synthetase, and the mammalian peptide chain release factor. The B. mori glycyl-tRNA synthetase also has sequence similarity with the Saccharomyces cerevisiae (cytoplasmic and mitochondrial), E. coli, and human threonyl-tRNA synthetases. This sequence similarity occurs in a sequence motif that is characteristic of other class II aminoacyl-tRNA synthetases. Two transcription start sites approximately 100 nucleotides apart were identified by ribonuclease mapping. One of the transcription start sites is used preferentially in the posterior silk gland. The peak in mRNA accumulation occurs 80-100 h prior to the peak in glycyl-tRNA synthetase activity and enzyme protein. PMID- 8463297 TI - Thermodynamics of monosaccharide binding to concanavalin A, pea (Pisum sativum) lectin, and lentil (Lens culinaris) lectin. AB - Titration calorimetry measurements of the binding of methyl alpha-D mannopyranoside (Me alpha Man), D-mannopyranoside (Man), methyl alpha-D glucopyranoside (Me alpha Glu), and D-glucopyranoside (Glu) to concanavalin A (Con A), pea lectin, and lentil lectin were performed at 281 and 292 K in 0.01 M dimethylglutaric acid-NaOH buffer (pH 6.9) containing 0.15 M NaCl and Mn+2 and Ca+2 ions. The site binding enthalpies, delta H, are the same at both temperatures and range from -28.4 +/- 0.9 (Me alpha Man) to -16.6 +/- 0.5 kJ mol 1 (Glu) for Con A, from -26.2 +/- 1.1 (Me alpha Man) to -12.8 +/- 0.4 kJ mol-1 (Me alpha Glu) for pea lectin, and from -16.6 +/- 0.7 (Me alpha Man) to -8.0 +/- 0.2 kJ mol-1 (Me alpha Glu) for lentil lectin. The site binding constants range from 17 +/- 1 x 10(3) M-1 (Me alpha Man to Con A at 281.2 K) to 230 +/- 20 M-1 (Glu to lentil lectin at 292.6 K) and exhibit high specificity for Con A where they are in the Me alpha Man:Man:Me alpha Glu:Glu ratio of 21:4:5:1, while the corresponding ratio is 5:2:1.5:1 for pea lectin and 4:2:2:1 for lentil lectin. The higher specificity for Con A indicates more interactions between the amino acid residues at the binding site and the carbohydrate ligand than for the pea and lentil lectin-carbohydrate complexes. The carbohydrate-lectin binding results exhibit enthalpy-entropy compensation in that delta Hb (kJ mol-1) = -1.67 +/- 0.06 x 10(4) + (1.30 +/- 0.12)T(K) delta Sb (J mol-1K-1). Differential scanning calorimetry measurements on the thermal denaturation of the lectins and their carbohydrate complexes show that the Con A tetramer dissociates into monomers, while the pea and lentil lectin dimers dissociate into two submonomer fragments. At the denaturation temperature, one carbohydrate binds to each monomer of Con A and the pea and lentil lectins. Complexation with the carbohydrate increases the denaturation temperature of the lectin and the magnitude of the increases yield binding constants in agreement with the determinations from titration calorimetry. PMID- 8463298 TI - Molecular cloning and expression of SmIrV1, a Schistosoma mansoni antigen with similarity to calnexin, calreticulin, and OvRal1. AB - Protective immunity against schistosomiasis induced by vaccination of mice with irradiated cercaria can be passively transferred to uninfected mice with sera or IgG. Antigens that are uniquely or more strongly recognized by such protective sera compared with sera from infected unprotected mice have been identified previously. Two genes, SmIrV1 and SmIrV5, were selected from an adult worm cDNA library by screening with antibodies raised against these candidate vaccine proteins. Active immunization with the SmIrV5 protein induces high levels of protection in mice. We report here the molecular cloning and sequencing of SmIrV1 which contains a deduced amino acid sequence of 582 residues with similarity to three proteins: calnexin, calreticulin, and OvRal1, a surface antigen of the filarial nematode Onchocerca volvulus. SmIrV1 can be divided into three regions: a neutral N-terminal region with a putative signal sequence, followed by a proline- and tryptophan-rich P region in which two sets of sequences are repeated four times and a C-terminal region which is highly acidic with an isoelectric point of 4.7. We expressed the P and C regions of SmIrV1 and showed that this polypeptide reacts with sera of immunized as well as chronically infected mice. PMID- 8463299 TI - Kinetic destabilization of the hydroperoxy flavin intermediate by site-directed modification of the reactive thiol in bacterial luciferase. AB - Bacterial luciferase catalyzes the formation of visible light, FMN, and a carboxylic acid from FMNH2, O2, and the corresponding aldehyde. The reactive cysteinyl residue at position 106 of the alpha subunit has been replaced by serine, alanine, and valine by site-directed mutagenesis (Baldwin, T. O., Chen L. H., Chlumsky, L. J., Devine, J. H., and Ziegler, M. M. (1989) J. Biolumin. Chemilumin. 4, 40-48) and the kinetics of the reaction catalyzed by each mutant protein measured by stopped-flow spectrophotometry at pH 7 and 25 degrees C. The time courses for the formation and decay of the various intermediates for the three alpha C106 mutants have been followed by monitoring the absorbance at 380 and 445 nm and the emission of visible light using n-decanal as the aldehyde substrate. The time courses for these events have been incorporated into a comprehensive kinetic model; 16 individual rate constants have been obtained for this model by numeric simulations of the time courses for the wild-type enzyme and for the three alpha C106 mutants. The mutants catalyzed the production of visible light demonstrating that the reactive thiol is not involved in the bioluminescence reaction. All three mutants have been found to catalyze the formation of the C4a-hydroperoxy flavin intermediate with rate constants equal to that of the wild-type enzyme. These results are incompatible with those reported by Xi et al. who have suggested that the major pathway for the oxidation of alpha C106V-bound FMNH2 does not involve the C4a-hydroperoxy flavin as an intermediate (Xi, L., Cho, K.-W., Herndon, M.E., and Tu, S.-C. (1990) J. Biol. Chem. 265, 4200 4203). The rates of decay of the C4a-hydroperoxy flavin intermediate with the mutant enzymes were found to be two orders of magnitude faster than that of the wild-type enzyme. Luciferase has been shown to be inhibited at high levels of aldehyde substrate when the enzyme is assayed by injecting FMNH2 into an aerobic mixture of enzyme and aldehyde. This aldehyde inhibition has been shown to occur by the formation of a dead-end enzyme-aldehyde complex which blocks the binding of FMNH2 to the enzyme; loss of activity is due to the rapid nonenzymatic decomposition of the reduced flavin with molecular oxygen. PMID- 8463300 TI - Mechanism of agonist-induced [Ca2+]i oscillations in pituitary gonadotrophs. AB - Gonadotropin-releasing hormone (GnRH) activates oscillatory Ca2+ signaling in pituitary gonadotrophs at a frequency (up to 25 min-1) that is dose-dependent and is determined by the degree of receptor-mediated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) formation. Similar dose-dependent and frequency-modulated Ca2+ oscillations were elicited by intracellular administration of Ins(1,4,5)P3 and its nonhydrolyzable analogs, consistent with models in which Ins(1,4,5)P3 levels determine the frequency of Ca2+ oscillations but do not fluctuate in synchrony with [Ca2+]i. At constant agonist concentrations, Ca2+ spiking varied in amplitude, with a number of progressively larger transients before the onset of maximal oscillations, followed by a gradual decrease in spike amplitude that was accompanied by an increase in spiking frequency. The decline in the amplitude and increase in frequency of Ca2+ transients during stimulation by GnRH were not related to a decrease in the propagation of the Ca2+ signal within the cell but were associated with gradual depletion of the agonist-sensitive Ca2+ pool. Once initiated, the pattern of Ca2+ spiking was not altered by blockade of receptor occupancy, by inhibition of phospholipase C, or by reduction of extracellular [Ca2+]. Also, the endoplasmic reticulum (Ca2+)-ATPase blocker, thapsigargin, could substitute for Ins(1,4,5)P3 in initiating the oscillatory Ca2+ response. These findings indicate that although the Ins(1,4,5)P3 concentration determines the pattern of transients at the initiation of the oscillatory Ca2+ signal, maintenance of the signal does not require a sustained rise in Ins(1,4,5)P3. Since the frequency of Ca2+ oscillations is also influenced by depletion of luminal [Ca2+], it is possible that the Ins(1,4,5)P3-sensitive channels in the endoplasmic reticulum are tonically inhibited by high intraluminal Ca2+ levels and that Ins(1,4,5)P3 surmounts such inhibition by promoting Ca2+ discharge. When a critical level of Ca2+ discharge is attained, repetitive Ca2+ transients are generated by an autocatalytic mechanism in which a sustained rise in Ins(1,4,5)P3 is not an essential requirement. PMID- 8463301 TI - Deletion between directly repeated DNA sequences measured in extracts of bacteriophage T7-infected Escherichia coli. AB - An in vitro system based upon extracts of bacteriophage T7 infected Escherichia coli was used to study genetic deletions and to examine the importance of DNA replication in the deletion process. When T7 genomes with gene 1.3 inactivated by a 43-bp insert of random sequence DNA bracketed by 11-bp direct repeats were replicated in vitro the inserts were deleted with a frequency of about 10(-5) deletions per genome replication. Under conditions where deletion could take place only by recombination between direct repeats on distinct DNA molecules deletion frequency was at least an order of magnitude lower. These data demonstrate the utility of the in vitro system as a means for examining deletion mechanisms and underscore the importance of DNA replication in deletions. PMID- 8463302 TI - 2',5'-Oligoadenylate-dependent RNase L is a dimer of regulatory and catalytic subunits. AB - The subunit composition of RNase L, a key enzyme in the interferon system, has been characterized. RNase L was purified from human Daudi cells on a column of 2 5A-Sepharose and used to immunize Balb/c mice. A specific monoclonal antibody which recognizes a protein of 80 kDa has been isolated. This protein has been characterized and shown to be an RNA-binding protein with nuclease activity which is associated with, but distinct from, the 80-kDa 2-5A-binding protein known previously as RNase L. It is therefore proposed that the 2-5A-dependent RNase L is a complex of two distinct subunits: an 80-kDa RNA-binding protein (i.e. the catalytic subunit) and an 80-kDa 2-5A-binding protein (i.e. the regulatory subunit). PMID- 8463303 TI - Inhibition of macrophage-mediated low density lipoprotein oxidation by stimulated rat serosal mast cells. AB - Mast cells and macrophages coexist in the human arterial intima where oxidation of low density lipoproteins (LDL) also takes place during atherosclerosis. To investigate whether mast cells play a role in macrophage-mediated oxidation of LDL, a model system was designed in which mast cells and macrophages were cocultured in incubation medium containing LDL. Stimulation of rat serosal mast cells to induce exocytosis of their cytoplasmic granules was found to inhibit macrophage-mediated oxidation of LDL. The inhibitory effect depended on the ability of mast cell-derived histamine, released from the exocytosed granules into the medium, to bind the copper ions necessary for propagation of the macrophage-initiated oxidation of LDL. In addition to binding free copper ions, the mast cell-derived histamine was also capable of inhibiting oxidation of LDL propagated by copper ions bound to the apolipoprotein B component of the LDL particle. The results indicate that mast cells may prevent cell-mediated oxidation of LDL and imply a potentially preventive role for the mast cell in atherosclerosis. PMID- 8463304 TI - Phosphorylation of peptide substrates for the catalytic subunit of cAMP-dependent protein kinase. AB - The steady-state kinetic parameters for the phosphorylation of four peptides by the catalytic subunit of cAMP-dependent protein kinase were measured as a function of pH. For peptides containing the minimum consensus sequence, R-R-X-S hyd (where hyd is a hydrophobic residue), the kcat/Kpeptide profile is bell shaped with pK values of 6.4 and 9.4. Inhibition studies with the peptide LRRNAI indicate that the lower pK corresponds to an intrinsic pK on the enzyme, whereas the higher pK is perturbed upward by 1 pH unit. Viscosity studies verify that substrate stickiness accounts for the kinetic perturbation of the higher pK in kcat/Kpeptide. Substitution of the P-3 arginine with alanine (where serine is the P-site) yields a kcat/Kpeptide versus pH profile that is also bell-shaped, although both pK values are intrinsic acid dissociation constants of the enzyme. Replacement of the P-2 arginine with alanine removes the lower pK in the pH-rate profile without altering the higher pK. These results indicate that recognition of the P-2 arginine requires the ionization of an enzyme residue. This result implies that if the catalytic subunit mechanism involves general base catalysis, the ionization of this bse is not manifested in the pH-rate profiles. PMID- 8463305 TI - Activation by G protein beta gamma subunits of beta-adrenergic and muscarinic receptor kinase. AB - We have shown previously that GTP-binding regulatory protein (G protein) beta gamma subunits stimulate the agonist- or light-dependent phosphorylation of muscarinic acetylcholine receptors (mAChRs) and rhodopsin by a protein kinase partially purified from porcine brain (mAChR kinase) but not the phosphorylation of rhodopsin by rhodopsin kinase (Haga, K., and Haga, T. (1992) J. Biol. Chem. 267, 2222-2227). We report here that the mAChR kinase phosphorylates beta adrenergic receptors (beta-ARs) purified from bovine lung in an agonist-dependent manner, and the phosphorylation is also stimulated by G protein beta gamma subunits. We also report that recombinant beta-adrenergic receptor kinase 1 (beta ARK1) expressed in COS-7 cells phosphorylates mAChRs (human m2 subtype) and rhodopsin in an agonist- or light-dependent manner, respectively, and that this phosphorylation is stimulated by G protein beta gamma subunits. By contrast, the beta gamma subunits do not stimulate the phosphorylation of mAChRs or rhodopsin by a beta-ARK1 mutant lacking a part of the carboxyl-terminal region which is present in beta-ARKs but not in rhodopsin kinase. These results indicate that the beta-ARK1 is the same as or very similar to the mAChR kinase but is distinguished from the rhodopsin kinase with respect to activation by the beta gamma subunits and that the extra carboxyl-terminal sequence in beta-ARKs is required for the stimulation by the beta gamma subunits. PMID- 8463306 TI - Kinetics of glucocorticoid receptor phosphorylation in intact cells. Evidence for hormone-induced hyperphosphorylation after activation and recycling of hyperphosphorylated receptors. AB - Glucocorticoid receptors are basally phosphorylated in the absence of hormone and become hyperphosphorylated after hormone treatment of intact cells. To determine the sequence of changes which the receptor undergoes following hormone binding, we analyzed the kinetics of receptor phosphorylation in WEHI-7 mouse thymoma cells and in stably transfected Chinese hamster ovary cells that overexpress the mouse receptor. No major differences were found between these two cell types. Cells were preincubated with 32P(i) and [35S] methionine to label the receptors metabolically. The phosphate content of the receptor protein was determined from the ratio of 32P to 35S in radioactive gel slices after immunopurification and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Hormone-induced increases in phosphorylation were seen as early as 5 min after adding hormone and persisted for 20 h. Analysis of newly formed cytosolic and nuclear-bound activated (DNA-binding) receptors showed that activation precedes hyperphosphorylation. Nonactivated receptors, both unliganded and hormone liganded, also became hyperphosphorylated but more slowly than activated receptors. The rate of receptor dephosphorylation, determined by chasing with unlabeled P(i), was much slower than the rate of phosphorylation or of hormone dissociation and appeared to be slightly increased by agonists and by the antagonist RU486 (which does not cause hyperphosphorylation). Mutant WEHI-7 cells lacking cAMP-dependent protein kinase activity gave basal and hormone-induced receptor phosphorylation indistinguishable from wild type cells. We conclude that (a) the substrate for hormone-dependent hyperphosphorylation is the activated hormone-receptor complex; (b) most hyperphosphorylated receptors are recycled and reutilized in hyperphosphorylated form; (c) control of receptor phosphorylation may not be cell-specific; (d) cAMP-dependent protein kinase is not involved directly or indirectly in phosphorylating major sites on the receptor in vivo. PMID- 8463307 TI - Inversion of the substrate specificity of yeast alcohol dehydrogenase. AB - The relationship between the size of the substrate binding pocket and the catalytic reactivities with varied alcohols was studied with the Saccharomyces cerevisiae alcohol dehydrogenase I (ScADH) and compared with the liver enzymes from horse (EqADH, EE isoenzyme) and monkey (MmADH alpha, alpha-isoenzyme). The yeast enzyme is most active with ethanol, and its activity decreases as the size of the alcohol is increased, whereas the activities of the liver enzymes increase with larger alcohols. The substrate pocket in ScADH was enlarged by single substitutions of Thr-48 to Ser (T48S), Trp-57 to Met (W57M), and Trp-93 to Ala (W93A), and a double change, T48S:W93A, and a triple, T48S:W57M:W93A. The T48S enzyme has the same pattern of activity (V/K) as wild-type ScADH for linear primary alcohols. The W57M enzymes have lowered reactivity with primary and secondary alcohols. The W93A and T48S:W93A enzymes resemble MmADH alpha in having an inverted specificity pattern for primary alcohols, being 3- and 10-fold more active on hexanol and 350- and 540-fold less active on ethanol, and are as reactive as the liver enzymes with long chain primary alcohols. The three Ala-93 enzymes also acquired weak activity on branched chain alcohols and cyclohexanol. PMID- 8463308 TI - Inhibition of glycolysis by amino acids in ascites tumor cells. Specificity and mechanism. AB - The effect of glutamine and asparagine on glucose metabolism has been studied in ascites tumor cells. Either of these amino acids decreased the glycolytic flux about 80%. Half-maximal effects were obtained with 0.14 mM glutamine and 0.087 mM asparagine. Among the 20 L-amino acids, only glutamate produced a similar effect. Glutamine and asparagine caused a 70% increase of hexose monophosphates and a large decrease of fructose-1,6-P2 and triose phosphates, evidencing a strong inhibition of the phosphofructokinase (EC 2.7.11) reaction. Analysis of the levels of various phosphofructokinase effectors revealed that fructose-2,6-P2 and AMP decreased 4-fold, phosphoenolpyruvate, citrate, and ATP increased 4-, 3-, and 1.8-fold, respectively, and that there was no change in ADP, Pi, and intracellular pH. Assay of phosphofructokinase at concentrations of substrates and effectors determined to be in the cells showed that the low activity of this enzyme could be accounted for by the change in the concentration of effectors, the major mechanism being the change in adenine nucleotides. The decrease in fructose-2,6-P2 contributed very little to the inhibition of phosphofructokinase activity. The effects of amino acids were prevented by amino-oxyacetate, suggesting that transamination was an obligatory step for these changes. PMID- 8463309 TI - Site-specific mutations in a loop region of the C-terminal domain of the large subunit of ribulose bisphosphate carboxylase/oxygenase that influence substrate partitioning. AB - Amino acids composing a flexible loop (loop 6) of the eight-stranded barrel domain of the L-subunit of Synechococcus ribulose bisphosphate carboxylase/oxygenase (EC 4.1.1.39) involved in reaction intermediate stabilization have been modified by site-specific mutagenesis. Changes at positions both distant and within the active site affect overall catalysis and substrate partitioning. Most significantly, replacement of the active site Lys (Lys-334) with Arg at the apex of the loop almost completely suppressed the carboxylase activity of the enzyme relative to oxygenation, with only a modest reduction in overall catalysis. Val-331 and Thr-342, more distant from the active site but with interacting side chains, were changed to larger and smaller residues with differential effects on both turnover and substrate partitioning. Substitution of the loop with the sequence found in more efficient carboxylases only increased partitioning marginally when accompanied by alterations in the C terminal tail of the L-subunit that interacts with the loop. Generally, modifications to the loop composition also affected enediol formation, the first step of catalysis, suggesting that the geometry and hence flexibility of this segment affect more than just stabilization of the intermediates immediately following reaction with CO2 or O2. PMID- 8463310 TI - The plastocyanin-deficient phenotype of Chlamydomonas reinhardtii Ac-208 results from a frame-shift mutation in the nuclear gene encoding preapoplastocyanin. AB - Ac-208 is a plastocyanin-deficient mutant of Chlamydomonas reinhardtii that contains only 2-3% of the wild-type level of plastocyanin-encoding mRNA and no detectable plastocyanin. Sequence analysis of the ac-208 plastocyanin-encoding gene reveals a single nucleotide insertion in the first exon compared with the wild-type gene; this alters the reading frame and results in a premature nonsense codon. We have introduced the genomic sequence encoding plastocyanin from a wild type strain into ac-208 by cotransformation with a selectable marker encoding nitrate reductase. Of 22 nit+ transformants characterized, nine contained additional plastocyanin-encoding sequences (compared with untransformed cells) and each of these nine transformants was found to accumulate the protein. Transformants that do not contain newly introduced plastocyanin sequences retain the plastocyanin-deficient phenotype. The introduced plastocyanin-encoding sequences are stable during mitotic growth in liquid culture over a period of several months, as is expression from the introduced sequences. We suggest that the decreased steady state level of plastocyanin-encoding messages is a consequence of the frame-shift mutation in the structural gene. The ability to complement ac-208 with plastocyanin-encoding sequences will allow the introduction and analysis of in vitro mutagenized plastocyanin sequences in vivo in transgenic C. reinhardtii cells. PMID- 8463311 TI - The adipocyte lipid-binding protein at 1.6-A resolution. Crystal structures of the apoprotein and with bound saturated and unsaturated fatty acids. AB - Crystals of the adipocyte lipid-binding protein which diffract to near atomic resolution have been obtained in Na/K phosphate buffer/precipitant system. The structures of the apo-form and the protein with bound oleic acid and stearic acid have been determined and refined to 1.6-A resolution with R-factor around 18%. The conformations of the bound fatty acids are nearly the same. In both cases, the carboxylate group of the ligand interacts directly with Arg126 and Tyr128, indirectly with Arg106 through a water molecule. The hydrocarbon tail sticks out of the protein surface through a hydrophobic patch. Saturated and unsaturated fatty acids bind in essentially the same conformation. The remaining space of the binding pocket is filled with well ordered water molecules interacting with most of the polar side chains. Comparisons between the holo- and apostructures reveal that the hydrophobic patch on the protein surface formed by a helix and several tight turns might serve as a portal for lipid binding. Since the adipocyte lipid binding protein is phosphorylated at Tyr19 by the insulin receptor kinase, the position of this side chain has been re-evaluated using the coordinates of the holo-forms. It appears that the position of Tyr19 does not change significantly upon the binding of either of the fatty acids. PMID- 8463312 TI - Modulation of ligand binding affinity of the adipocyte lipid-binding protein by selective mutation. Analysis in vitro and in situ. AB - The crystal structure of the adipocyte lipid-binding protein (ALBP) with coordinated fatty acid shows the hydrophobic ligand bound within a water-filled central cavity with its carboxyl group engaged in a hydrogen bonding network involving, at least in part, the functional groups of residues R126 and Y128. We produced mutant forms of ALBP which altered these amino acids, expressed these in Escherichia coli as glutathione S-transferase (GST) fusion proteins, and examined their ligand-binding properties using the fluorescent fatty acids cis-parinaric acid (c-PA) and 12-(9-anthroyloxy)-oleate (12-AO). The wild-type and all mutated forms of GST-ALBP displayed similar binding affinities for 12-AO, with Kd,app values ranging from 0.5 to 2.4 microM. The binding affinity of ALBP forms R126Q and Y128W for c-PA were reduced about 30-50-fold in comparison to GST-ALBP, while that for the double mutation R126L + Y128F was below the limits of detection. To determine if the hydrogen bonding system functioned in situ, Chinese hamster ovary (CHO) cell transfectants expressing wild-type ALBP demonstrated a moderate (1.5-2-fold) increase in the total rate of [3H]oleate uptake and trafficking into the esterified lipid pools over that of untransfected cells, while the rate of [3H]oleate uptake of the transfected CHOs expressing the R126L + Y128F mutation was identical to that of the control CHOs. In summary, these results suggest that the primary factor contributing to binding affinity of ALBP for fatty acids such as c-PA or oleic acid both in vitro and in situ is the hydrogen bonding network involving at least R126, Y128, and the lipid carboxyl group. However, a ligand with sufficiently large hydrophobic character such as 12-AO can bind in the absence of a functional carboxylate hydrogen bonding network, presumably due to stabilizing entropic interactions with other cavity atoms. PMID- 8463313 TI - Induction of Sp1-p53 DNA-binding heterocomplexes during granulocyte/macrophage colony-stimulating factor-dependent proliferation in human erythroleukemia cell line TF-1. AB - The involvement of Sp1 in regulating cell proliferation in myeloid leukemia cells was determined by measuring the levels and DNA binding activity of Sp1 in TF-1 cells, a human erythroleukemia cell line dependent on granulocyte/macrophage colony-stimulating factor (GM-CSF) for viability and cell growth. DNA binding of Sp1 to a specific double-stranded oligodeoxynucleotide was increased markedly in a dose-dependent manner in proliferating cells in response to GM-CSF compared with growth-arrested or apoptotic cells. Competition experiments and mobility shift interference assays with antibodies against Sp1 as well as wild-type or mutant p53 indicated that GM-CSF-inducible DNA-binding complexes contained both Sp1 and p53 and that these heterocomplexes bound to both p53- and Sp1-binding sequences with high affinity. Immunoprecipitation of nuclear extracts with a p53 antibody indicated that Sp1 was associated as a heterocomplex with p53. Formation of this complex was dependent on the level of p53 since p53 was more abundant in proliferating cells and decreased upon induction of growth arrest and apoptosis by withdrawal of GM-CSF while Sp1 levels remained unchanged. These results suggest that the association of Sp1 with p53 may represent a novel mechanism of growth regulation in cytokine-dependent leukemia cells. PMID- 8463314 TI - Differential binding of retinol analogs to two homologous cellular retinol binding proteins. AB - A comparative study of the interactions of rat cellular retinol-binding protein (CRBP) and cellular retinol-binding protein II (CRBP II) with a number of synthetic phenyl-substituted analogs of all-trans-retinol was performed using fluorescence and nuclear magnetic resonance analysis. These studies indicate that CRBP II is more sensitive to modifications of the ring moiety than CRBP. Removal of the two methyl substituents on the ring which are ortho to the polyene chain abolishes binding to CRBP II. Conformational analysis of the ligands indicates that these two methyl groups influence the planarity of the ligand. The identification of monospecific ligands may prove useful for studying the physiological roles of these two proteins. PMID- 8463315 TI - Mutations in a zinc-binding domain of human insulin-degrading enzyme eliminate catalytic activity but not insulin binding. AB - Insulin-degrading enzyme is a nonlysosomal metalloprotease that initiates degradation of internalized insulin in some cells. We previously identified a potential catalytic site containing an inversion of the Zn(2+)-binding domain of the thermolysin family (Kuo, W.-L., Gehm, B. D., and Rosner, M. R. (1991) Mol. Endocrinol. 4, 1580-1591). The role of this site in catalysis was examined by mutating one of the presumptive Zn(2+)-coordinating histidines (His108) in human insulin-degrading enzyme to leucine or glutamine, which were predicted to reduce or eliminate Zn2+ binding without substantially altering secondary structure. cDNAs for the mutant and wild-type enzymes were incorporated into an expression vector and transfected into COS cells. Expression of the transfected genes was confirmed by Northern and Western blots. In contrast to the wild-type gene, which increased insulin degradation by cell extracts and intact cells several-fold, the mutated genes had no effect on insulin degradation, indicating a loss of catalytic activity. However, the mutants' ability to bind substrate was unimpaired, as affinity labeling with 125I-insulin was increased compared to the wild type. These results suggest that an intact Zn(2+)-binding domain in human insulin-degrading enzyme is required for catalytic activity and can affect, but is not required for, substrate binding. PMID- 8463316 TI - Ca2+, caldesmon, and myosin light chain kinase exchange with calmodulin. AB - Wheat calmodulin (CaM) was labeled at Cys-27 with the sulfhydryl-specific fluorescent probe 2-(4'-maleimidoanilino)-naphthalene-6-sulfonic acid (MIANS), to form MIANS.CaM. In the presence of Ca2+, MIANS.CaM undergoes a large fluorescence increase when it binds myosin light chain kinase (MLCK) and caldesmon (CaD), but little fluorescence change when it binds CaM antagonists or Ca2+. MLCK associates with MIANS.CaM at a rate of 2.8 x 10(7) M-1 s-1 and dissociates at 0.031 s-1 (Kd = 1.1 nM). Protein kinase A phosphorylation of MLCK (P-MLCK) produces a 3.5-fold decrease in its association rate with CaM and a 6-fold increase in its dissociation rate (Kd = 23 nM). CaD associates with MIANS.CaM with a rate of 5.3 x 10(8) M-1 s-1 and dissociates at 57 s-1 (Kd = 108 nM). EGTA disrupts the CaM.MLCK, CaM.P-MLCK, and the CaM.CaD complexes at rates of 3.5 s-1, 6.5 s-1, and 13.5 s-1, respectively. MLCK, therefore, dissociates from CaM more quickly by Ca2+ removal while the lower affinity CaD is dissociated more quickly by competition from higher affinity CaM target proteins than by Ca2+ removal. MLCK binding to CaM slowed Ca2+ dissociation from CaM's C-terminal Ca(2+)-binding sites from 30 s-1 to 6 s-1 while CaD had little effect on Ca2+ dissociation from these sites. During a Ca2+ transient, CaM could exchange with MLCK and CaD rapidly enough for these proteins to be directly involved in the contraction/relaxation cycle of smooth muscle. PMID- 8463317 TI - Enzymatic studies of lyso platelet-activating factor acylation in human neutrophils and changes upon stimulation. AB - Resting human neutrophils acylate 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (1 O-alkyl-2-lyso-GPC; lyso-PAF) specifically with arachidonate (AA); upon stimulation, however, the specificity is lost and other fatty acid residues are added. The major goals of this study were to compare the various acylation reactions present in the cells and to determine the cause of the specificity loss upon stimulation. The CoA-independent transacylase was active in neutrophil homogenates and was found to be both highly specific for AA and stereospecific, requiring 1-O-alkyl-2-lyso-GPC for activity. Homogenates also contained acyl CoA:1-radyl-2-lyso-sn-glycero-3-phosphocholine acyltransferase activity, which transferred acyl chains from oleoyl-, linoleoyl-, or linolenoyl-CoA to both 1 alkyl and 1-acyl acceptors, but preferred the 1-acyl acceptor when arachidonoyl CoA was used. The CoA-dependent and -independent activities co-sedimented on a discontinuous Percoll gradient in a single band containing plasma membrane and possibly other membranes. CoA alone promoted nonspecific acylation in the homogenates. The AA-specific acylation was attenuated up to 80% in sonicates of ionophore-stimulated cells, whereas the CoA-dependent acyltransferase remained unchanged. Potential phospholipid AA donors for the transacylase were substantially depleted in the stimulated cells but could not account for the large decrease in acylation. An accumulation of 1-O-alk-1'-enyl-2-lyso-sn-glycero 3-phosphoethanolamine (alkenyl-2-lyso-GPE), which acts as a competing substrate, appeared to be the major cause of the reduced AA-specific acylation of lyso-PAF observed in the stimulated preparations. Removal of the alkenyl-2-lyso-GPE restored the activity, whereas the addition of alkenyl-2-lyso-GPE (2 microM) to resting membrane preparations resulted in a marked decrease in transacylation of lyso-PAF. PMID- 8463318 TI - Differences in microtubule binding and self-association abilities of bovine brain tau isoforms. AB - We have fractionated tau isoforms by elution at increasing pH values using iron chelated affinity chromatography, which discriminates between isoforms phosphorylated to different extents. Microtubule-associated tau elutes from the column at a pH gradient narrower than that of total brain tau. Neither under phosphorylated nor highly phosphorylated isoforms are found in the microtubule associated tau protein preparation. This indicates that phosphorylation at certain sites is needed for tau binding to microtubules, whereas phosphorylation at some other sites may prevent the association. The self-association ability of the different tau isoforms has also been analyzed. Tau isoforms containing three tubulin binding motifs form covalently bound dimers more efficiently than tau isoforms containing four motifs. This dimer-forming ability is notably diminished in the presence of a reducing agent, as determined by SDS-polyacrylamide gel electrophoresis, thus suggesting the involvement of cysteine residues. Additionally, tau forms larger aggregates, as detected by gel permeation chromatography, which are solubilized by SDS and cannot, therefore, be observed by SDS-polyacrylamide gel electrophoresis. These tau aggregates are observed even in the presence of reducing agents. These results support the idea that other regions in the tau molecule, besides the Cys-containing tubulin binding region, also contribute to tau self-association. Tau dimerization and aggregation may be prior steps to the formation of paired helical filaments. PMID- 8463319 TI - Repair of aflatoxin B1 DNA adducts by the UvrABC endonuclease of Escherichia coli. AB - The repair by UvrABC endonuclease of two major adducts formed by aflatoxin B1 in DNA was found to be similar. Aflatoxin epoxide was used to generate the aflatoxin B1.N7-guanine adduct which can convert to aflatoxin B1-formamidopyrimidine adduct. The reaction of the aflatoxin B1 epoxide with DNA follows pseudo-first order kinetics. The DNA sequence-specific relative reactivity of the epoxide is the same as previously observed for aflatoxin B1 activated by liver microsomes, therefore strongly reinforcing the notion that aflatoxin B1 reacts with DNA through the epoxide intermediate. For the majority of lesion sites, a high affinity protein-DNA complex was formed from the UvrA and the UvrB proteins with similar efficiency to both adducts, and to pyrimidine dimers, and then nicks the DNA when UvrC was added. The two incisions are at the eighth phosphodiester moiety 5' and the sixth phosphodiester moiety 3' of a modified guanine nucleotide. Both incisions appeared to be concerted. For some sites, the DNA sequence can alter the relative incision efficiency up to 15-fold. However, the majority of these AFB1 lesion structures in most DNA sequences are similar with respect to recognition by this nucleotide excision repair enzyme. Therefore the observation that the aflatoxin B1.N7-guanine lesion is removed rapidly, while the aflatoxin B1-formamidopyrimidine lesion persists in the mammalian cell may have other mechanistic explanations. PMID- 8463320 TI - Binding and phasing of Escherichia coli single-stranded DNA-binding protein by the secondary structure of phage G4 origin of complementary DNA strand synthesis (G4oric). AB - The origin of phage G4 DNA complementary strand synthesis (G4oric) consists of three stem-loop structures (stem loops I, II, and III) that have been proposed as a recognition site for primase during primer RNA (pRNA) synthesis (Godson, G. N., Barrell, B. G., Staden, R., and Fiddes, J. C. (1978) Nat. New Biol. 276, 236-247; Fiddes, J. C., Barrell, B. G., and Godson, G. N. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 1081-1085; Sims, J., Capon, D., and Dressler, D. (1979) J. Biol. Chem. 254, 12615-12628). It is generally considered that the double-stranded DNA stem loop structure is not coated with Escherichia coli single-stranded DNA-binding protein (SSB), but is recognized by primase as naked DNA (Kornberg, A., and Baker, J. (1992) DNA Replication, 2nd Ed., p. 280, W. H. Freeman & Co., New York). Using small G4oric single-stranded DNA fragments of various sizes (302, 278, 149, and 100 nucleotides) consisting of the core 100-nucleotide stem-loop region plus differing lengths of 3'- and 5'-flanking sequence as substrates for gel retardation and DNase I and micrococcal nuclease digestion, we show that under conditions of pRNA synthesis, two SSB tetramers bind to the stem-loop structure. With increasing lengths of 5'- and 3'-flanking sequence, more SSB tetramers are added. Regardless of the number of SSB tetramers bound, however, the region of DNA containing the pRNA initiation site is always left accessible to nuclease digestion. In situ copper-phenanthroline footprinting of individual gel shift assembly intermediates shows that on the 302-nucleotide G4oric, the first two SSB tetramers assemble at random, but the addition of more SSB tetramers results in formation of a unique structure. In this structure, SSB tetramers protect both sides of stem loop III plus the intervening region between stem loops III and I, but leave most of stem loop I and the CTG pRNA initiation site accessible to copper-phenanthroline. Primase can only synthesize pRNA when the stem-loop structure is saturated with SSB and presumably in the unique configuration. The G4oric stem-loop structure therefore appears to dictate the phasing of SSB to leave a primase recognition site as free DNA. PMID- 8463321 TI - Induction of basic fibroblast growth factor mRNA and protein synthesis in smooth muscle cells by cholesteryl ester enrichment and 25-hydroxycholesterol. AB - Basic fibroblast growth factor (bFGF) is a potent smooth muscle cell mitogen. Smooth muscle cell and macrophage-derived foam cells, resulting from cholesteryl ester accretion, are hallmark characteristics of atherosclerosis. We wanted to determine if bFGF synthesis is altered during cholesteryl ester accumulation in smooth muscle cells. Cholesteryl ester enrichment causes a 3-fold increase in bFGF in cellular lysates and a 3-fold increase in steady state mRNA levels for bFGF, as compared with control cells. Conditioned media from cholesteryl ester enriched smooth muscle cells contains 6 times more mitogenic activity than conditioned media from control cells; this activity is neutralized by an antibody directed against bFGF but not by an antibody directed against platelet-derived growth factor. These results suggest that cholesteryl ester enrichment also enhances bFGF release. Since oxysterols have been implicated in the pathogenesis of atherosclerosis, we determined if oxysterols could affect bFGF production and release. 25-Hydroxycholesterol also increases the release of bFGF-like mitogens from smooth muscle cells, as well as increasing mRNA transcript levels for bFGF. Cholesteryl ester enrichment and 25-hydroxycholesterol did not promote bFGF release secondary to cell injury. In conclusion, these data define a basic mechanism for smooth muscle cell hyperplasia during atherogenesis involving the generation of bFGF by smooth muscle cell-derived foam cells. PMID- 8463322 TI - Covalently immobilized laminin peptide Tyr-Ile-Gly-Ser-Arg (YIGSR) supports cell spreading and co-localization of the 67-kilodalton laminin receptor with alpha actinin and vinculin. AB - The laminin-based nonapeptide Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg (CDPGYIGSR) and pentapeptide Tyr-Ile-Gly-Ser-Arg (YIGSR) have been previously demonstrated to support the attachment of several cell types and to competitively bind to the 67 kDa high affinity laminin receptor. Cell attachment, but not spreading, on substrates containing adsorbed CDPGYIGSR or YIGSR was observed. In this report we describe YIGSR-mediated attachment and spreading of a wide variety of cell types. GYIGSRY promoted cell spreading and stress fiber formation when it was covalently immobilized through the amino-terminal Gly residue, used as a spacer arm. Spreading was not observed when adsorbed YIGSR peptide was used. Functionally blocking antiserum directed against the 67-kDa and related laminin-binding proteins blocked human foreskin fibroblast (HFF) spreading, but not attachment, on covalently grafted GYIGSRY substrates. However, functionally blocking antisera directed against the vitronectin receptor, integrin alpha v beta 3, and the fibronectin receptor, integrin alpha 5 beta 1, did not affect HFF spreading on these substrates. When HFFs spread on these substrates, the 67-kDa laminin receptor co-localized with the cytoplasmic proteins alpha-actinin and vinculin into discrete structures. These results suggest that the adhesion ligand YIGSR is solely sufficient for cell spreading when it is conformationally constrained by covalent attachment to a solid substrate, at least when attached via its amino terminus. Furthermore, the role of the 67-kDa laminin receptor in recognition of this ligand and mediating cell attachment is confirmed in this study. This report also provides the first evidence for direct or indirect association of this receptor with vinculin and alpha-actinin when YIGSR-mediated cell spreading occurs. PMID- 8463323 TI - The identification, purification, and characterization of two invariant surface glycoproteins located beneath the surface coat barrier of bloodstream forms of Trypanosoma brucei. AB - Two new polypeptides, termed ISG70 and ISG64, have been found in Trypanosoma brucei, using enzyme-catalyzed radioiodination techniques. Both are externally disposed integral membrane glycoproteins, containing N-linked carbohydrate chains. No structural homology was detected between ISG70, ISG64, or the variant surface glycoprotein (VSG) when assessed by 1) comparative peptide mapping, 2) immunoprecipitation analysis, and 3) lectin affinity chromatography. ISG70 occurred in 5.1 x 10(4) copies/cell and has been purified 880-fold from detergent extracts of plasma membranes by a procedure that includes gel filtration, lectin affinity chromatography, and preparative SDS-polyacrylamide gel electrophoresis. ISG70 was present only in bloodstream forms and was specifically detected in six different cloned variants from the Molteno Institute trypanosomal antigen type (MITat) serodeme of T. brucei and from the single cloned variant of the International Laboratory for Research on Animal Diseases trypanosomal antigen type (ILTat) serodeme that was examined. Rabbits with chronic infections of T. brucei displayed circulating antibodies against ISG70. Both the immunogenicity of ISG70 and its invariant nature suggest that it may be useful in the development of an effective serodiagnostic test. Furthermore, its stage-specific location combined with its invariant nature implies that its function is strictly related to a physiological role required for the parasite's residence in its mammalian host. PMID- 8463324 TI - Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase alpha-primase complex and their gene expression during cell proliferation and the cell cycle. AB - The DNA polymerase alpha-primase complex purified from mouse FM3A cells is composed of four polypeptides with molecular masses of 180, 68, 54, and 46 kDa. The largest subunit has DNA polymerase activity, the two smallest subunits have DNA primase activity, and the function of the 68-kDa subunit is unknown. We have isolated the cDNAs of the four subunits by low stringency hybridization and reverse transcription polymerase chain reaction and determined their nucleotide sequences. The predicted amino acid sequence of the 180-kDa subunit shows 88, 38, 34, and 32% identity to those of the catalytic subunits of human, Drosophila melanogaster, Schizosaccharomyces pombe, and Saccharomyces cerevisiae DNA polymerase alpha, respectively, and contains seven regions whose orders and sequences are highly conserved among viral and other eukaryotic DNA polymerases. The deduced amino acid sequence of the 68-kDa subunit shows 25% identity to that of the 73-kDa subunit of D. melanogaster DNA polymerase alpha-primase, shows no significant sequence similarity to any other protein in the data bases, but contains a potential phosphorylation site(s) for cdc2 kinase. The amino acid sequence of the 54-kDa subunit shows 32% identity to that of the large subunit of S. cerevisiae DNA primase. During activation of quiescent Swiss mouse 3T3 cells to proliferate, the levels of mRNA of the four subunits of the DNA polymerase alpha-primase complex increased before DNA synthesis. In growing mouse FM3A cells, the transcripts of the four subunits are present throughout the cell cycle and increase slightly prior to the S phase. PMID- 8463325 TI - Quiescence-dependent activation of the p20K promoter in growth-arrested chicken embryo fibroblasts. AB - We described the synthesis of a quiescence-specific p20K protein in quiescent chicken heart mesenchymal cells and contact-inhibited chicken embryo fibroblasts (Bedard, P.-A., Balk, S.D., Gunther, H.S., Morisi, A., and Erikson, R.L. (1987a) Mol. Cell. Biol. 7, 1450-1459). We now report that the expression of p20K is enhanced in cells rendered quiescent by other conditions of growth arrest such as serum starvation or treatment with hydroxyurea. Chicken embryo fibroblasts transformed by the Rous sarcoma virus also expressed p20K upon serum/medium depletion. In all conditions investigated, the synthesis of p20K was correlated with decreased DNA synthesis, indicating that growth arrest regulates the expression of p20K in fibroblasts. The abundance of p20K mRNAs was elevated in quiescent cells, and the p20K gene was more active in nuclear run-on transcription assays in conditions of growth arrest. The p20K gene was isolated, and the promoter region was analyzed in transient expression assays. Serum starvation increased the activity of the promoter, indicating that the expression of p20K is controlled at least in part at the transcriptional level. Deletion analysis revealed that a region of less than 217 base pairs (bp) is sufficient for quiescence-dependent activity of the promoter. Within this region, a segment of 48 bp was essential to basal and quiescence-induced activity of the promoter in dividing and nondividing cells, respectively. The 48-bp region enhanced the activity of a minimal heterologous promoter in quiescent cells but had no effect in conditions of proliferation, indicating that it functions as a quiescence responsive unit (QRU). Therefore, the transcription of the p20K gene in quiescent fibroblasts is controlled by the one or several growth-regulated elements located in the 48-bp QRU of the promoter. PMID- 8463326 TI - Folding and assembly of bacterial alkaline phosphatase in vitro and in vivo. AB - Alkaline phosphatase (PhoA), localized in the periplasmic space of Escherichia coli, is a homodimeric metalloprotein containing two intramolecular disulfide bonds. We attempted to clarify the folding-assembly pathways of this enzyme by allowing in vitro-synthesized PhoA polypeptide to fold into active enzyme and by examining the occurrence of similar pathways in vivo by pulse-chase experiments. PhoA (lacking the signal sequence) that was synthesized in a coupled transcription-translation system was effectively converted into active enzyme when incubated with either oxidized glutathione, periplasmic proteins, or purified DsbA protein in the presence of Zn2+. The first appreciable event in the activation of initially unfolded translation product (species I) was the disulfide bond formation, which was immediately followed by folding into a partially trypsin-resistant monomer (species II), and then by assembly into active dimer (species III). The species II PhoA molecules, but not the species III molecules, were found to be sensitized to trypsin in the presence of a reducing agent, dithiothreitol. Pulse-chase studies showed that PhoA acquires disulfide bonds immediately after the biosynthesis, whereas it acquires resistance to both dithiothreitol and certain endogenous protease over some 2 min at 15 degrees C. These results indicate that PhoA undergoes a series of folding assembly steps, some of which are of measurable speeds in vivo and mimicable in vitro. PMID- 8463327 TI - Testicular temperature-labile cholesteryl ester hydrolase. Relationship to isoenzymes from other tissues, correlation with spermatogenesis, and inhibition by physiological concentrations of divalent cations. AB - Temperature-labile cholesterol ester hydrolase (TLCEH) was purified 2,000-fold from rat testis cytosol using sequential ammonium sulfate precipitation, cation exchange chromatography, and isoelectric focusing chromatography. the purified enzyme, which exhibited a single silver-stained band (66 kDa) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was inhibited 89% by the elevation of the temperature from 32 to 37 degrees C and 65% by treatment with alkaline phosphatase. Its amino acid composition and amino-terminal sequence differed markedly from those of isoenzymes from other tissues, although 6 of 20 residues were conserved. Polyclonal antibodies raised to TLCEH exhibited no cross immunoreactivity with cytosolic proteins from other rat tissues and inhibited 70% of testis cytosolic CEH. Western blot analysis demonstrated a high correlation between immunoreactive protein and catalytic activity in the testis during maturation of the rat, with a marked increase at the onset of spermatogenesis. TLCEH was inhibited by physiological levels of Cu2+ (I50 = 0.60 microM) and Zn2+ (I50 = 0.75 microM) and by Cd2+ (I50 = 0.15 microM) but not by 0.5-5 mM Mn2+. PMID- 8463328 TI - Analysis of the functions of the first epidermal growth factor-like domain of factor X. AB - Upon activation, factor X participates in the prothrombin activation complex. Similar to 4-carboxyglutamic acid (Gla)-domainless protein C, the Gla-domainless factor X (GDFX) contains a high affinity Ca(2+)-binding site critical for the function of these molecules. In the case of protein C, we recently demonstrated that the high affinity Ca(2+)-binding site critical for activation is outside the first epidermal growth factor (EGF) homology domain. To examine if this is also true for factor X, we have expressed in human 293 cells a deletion mutant of factor X (E2FX) which lacks the entire Gla region as well as the NH2-terminal EGF homology region of factor X. Direct binding studies by equilibrium dialysis indicate that E2FX contains a single Ca(2+)-binding site with a dissociation constant (Kd) of 154 +/- 48 microM. The functional properties of E2FX are equivalent or improved over those of GDFX. For instance, the factor X coagulant protein of Russell's viper venom activates E2FX three times faster than recombinant GDFX. Kinetic analysis of prothrombin activation in the absence of membranes indicates that activated GDFX and E2FX bind to factor Va with equal affinity (Kd = 4.1 microM). The Ca2+ concentration required for half-maximal prothrombin activation rates in the above activation system shifted from 721 +/- 113 microM for activated GDFX to 193 +/- 64 microM for activated E2FX. GDFX and E2FX activation rates with the soluble tissue factor-factor VIIa complex were identical as was the Ca2+ dependence of the reaction. We conclude that E2FX retains a high affinity Ca(2+)-binding site and that the first EGF homology domain does not appear to have a positive functional role in the GDFX molecule. However, Ca2+ occupancy of the Ca(2+)-binding site in the first EGF domain of intact factor X may be essential for optimal prothrombin activation. PMID- 8463329 TI - Membrane vesicles containing overproduced SecY and SecE exhibit high translocation ATPase activity and countermovement of protons in a SecA- and presecretory protein-dependent manner. AB - Everted membrane vesicles were prepared from Escherichia coli cells containing either overproduced amounts (OP-membrane vesicles) or normal amounts (normal membrane vesicles) of SecY and SecE, both of which are essential components of the protein translocation apparatus. The rates of translocation of pro-OmpA were similar in the two types of membrane vesicles, whereas translocation ATPase activity, which requires SecA, a precursor protein (pro-OmpA), and membrane vesicles, was appreciably higher with OP-membrane vesicles than with normal membrane vesicles. Since ATP hydrolysis has been shown to take place at an earlier part of the translocation reaction, these results suggest that the overproduction of SecY and SecE enhanced the activity of the earlier process, but not the entire process, of the translocation reaction. The addition of pro-OmpA in the presence of SecA caused the partial collapse of delta pH (inside acidic) generated on OP-membrane vesicles, suggesting that protons come out from the inside of the membrane vesicles in a pro-OmpA-dependent manner. The collapse of delta pH caused by pro-OmpA required SecA, ATP, and SecY and was not detected when normal membrane vesicles were used. These results indicate that the early event of protein translocation, which requires the functioning of SecA, SecY, and SecE, causes the countermovement of protons. PMID- 8463330 TI - Oxidized ATP. An irreversible inhibitor of the macrophage purinergic P2Z receptor. AB - The effects of oxidized ATP (oATP) on responses triggered by extracellular adenosine 5'-triphosphate (ATPe) were investigated in the mouse macrophage-like cell line J774. ATPe induced in this cell line two kinds of responses mediated by two different P2 purinergic receptors: 1) an early permeabilization of the plasma membrane to extracellular hydrophilic markers of M(r) up to 900 mediated by P2Z receptors; and 2) a fast mobilization of Ca2+ from intracellular stores mediated by P2Y receptors. Low oATP concentrations (100 microM) completely blocked the first response without affecting the second. ATPe-dependent cell swelling, vacuolization, and lysis were also inhibited. Antagonism developed slowly, as an incubation at 37 degrees C for at least 2 h in the presence of oATP was needed and was irreversible, thus suggesting that the inhibitory action was due to covalent modification of the receptor. The rate of hydrolysis of exogenous ATP was slightly decreased by oATP, indicating a minor blocking effect of this compound on plasma membrane ecto-ATPases in the concentration range tested. These observations suggest that oATP may be a potentially very useful tool for isolation and characterization of the P2Z purinergic receptor. PMID- 8463331 TI - Partial revertants of tryptophan synthetase alpha chain active site mutant Asp60- >Asn. AB - Residue Asp60 of the tryptophan synthetase alpha chain of Escherichia coli is though to interact with the pyrrole NH of substrate indole-3-glycerol phosphate and facilitate its cleavage to indole and glyceraldehyde 3-phosphate. Two distinguishable partial revertants of DN60 tryptophan synthetase alpha mutant trpA34 were analyzed. The slower growing partial revertant, PR1, had the second site change, YD102. The other partial revertant, PR2, lacked three consecutive base pairs, resulting in replacement of Ala59 and Asn60 of the DN60 mutant alpha polypeptide by Asp. Inspection of the three-dimensional structure of the enzyme substrate analog complex revealed that Tyr102 is in the vicinity of the pyrrole NH of the substrate. The PR1 alpha chain has a near normal Km for substrate, whereas the PR2 polypeptide has greatly reduced substrate affinity. The PR2 polypeptide is more active than the PR1 polypeptide in the alpha beta reaction in vitro and appears to be more active than the PR1 polypeptide in vivo. Attempts to obtain repeat occurrences of the PR2 deletion mutation were unsuccessful. A third type of trpA34 partial revertant, PR3, that grows very poorly in minimal medium, also has a Tyr102 replacement: YF102. These findings demonstrate that each of the second-site mutations affects a residue located in the vicinity of the active site residue altered by the primary mutation. Slightly leaky mutant trpA89, genetically altered near the site of the trpA34 mutation, was found to have a GS61 substitution. PMID- 8463332 TI - Evidence that the CryIA crystal protein from Bacillus thuringiensis is associated with DNA. AB - Toxin generated by activation of the Bacillus thuringiensis CryIA(c) crystal protein (protoxin) with bovine trypsin was separated into two components by anion exchange chromatography. One component (T2) was DNA-associated toxin, and the other was the DNA-free toxin (T1). Only one major protoxin component was observed, and it was found to be associated with DNA. The DNA from the T2 toxin varied in size from 100 to 300 base pairs, whereas the crystal and the solubilized protoxin contained 20-kilobase DNA as the major DNA component. DNase treatment converted the T2 toxin to the DNA-free T1 toxin. In contrast, the DNA in the crystal and the solubilized protoxin was resistant to DNase digestion and was not dissociated from the protein by 1.5 M NaCl. The protoxin and DNA appeared to elute as a complex with a molecular mass of > 2 x 10(6) Da on gel-filtration chromatography. No toxin was generated from the protoxin with trypsin after extensive digestion of the protoxin with DNase or dissociation of the DNA by succinylation of the lysine residues. It is proposed that DNA binds to the COOH terminal half of the crystal protein and is essential for maintaining the conformational integrity required for crystal formation and generation of toxin. PMID- 8463333 TI - Molecular cloning of a novel melanocortin receptor. AB - Using the technique of the polymerase chain reaction primed with oligonucleotides based on the homologous transmembrane regions of seven transmembrane G protein linked receptors, we isolated three full-length human genes that encode a novel subgroup of this receptor family. Recently, two of these receptors were identified as specific for alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone. We report the molecular cloning and pharmacologic characterization of a third member of this subgroup. The gene for this receptor encodes a protein of 361 amino acids in length. Its pharmacology characterizes it as an MSH receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. By Northern blot hybridization and polymerase chain reaction, it is expressed in brain, placental, and gut tissues but not in melanoma cells or in the adrenal gland. These findings may yield insight into the physiology of peptides derived from pro opiomelanocortin post-translational processing. PMID- 8463334 TI - Myristoylation of proteins in platelets occurs predominantly through thioester linkages. AB - We have demonstrated by several lines of evidence that in platelets myristate is linked to proteins predominantly via thioester bonds as is palmitate, and the covalent binding of the two long chain saturated fatty acids to proteins involves the same mechanisms. The first piece of evidence to support the thioester linkage between myristate and proteins is that [3H]myristate could be removed from proteins via alkaline methanolysis, which disrupts ester bonds but not amide bonds. The second piece of evidence is that unlabeled palmitate, which can form only thioester bonds in physiologic concentrations, competitively inhibits the formation of alkaline methanolysis-sensitive covalent bonds between [3H]myristate and proteins. Third, by SDS-polyacrylamide gel electrophoresis and fluorography, the patterns of labeled proteins from [3H]myristate- and [3H]palmitate-labeled platelets are identical. Fourth, [3H]myristate-labeled proteins, like [3H]palmitate-labeled proteins, both release their fatty acid moieties when exposed to hydroxylamine at neutral pH, which disrupts thioester but not hydroxyester bonds. These findings indicate that although the covalent binding of palmitate to proteins was found to occur at a faster rate than that of myristate, protein S fatty acid acylation that occurs posttranslationally is not specific for palmitate. PMID- 8463335 TI - The binding site for the beta gamma subunits of heterotrimeric G proteins on the beta-adrenergic receptor kinase. AB - The beta gamma subunits of heterotrimeric G proteins play important roles in regulating receptor-stimulated signal transduction processes. Recently appreciated among these is their role in the signaling events that lead to the phosphorylation and subsequent desensitization of muscarinic cholinergic (Haga, K., and Haga, T. (1992) J. Biol. Chem. 267, 2222-2227) and beta-adrenergic (Pitcher, J. A., Inglese, J., Higgins, J. B., Arriza, J. L., Casey, P. J., Kim, C., Benovic, J. L., Kwatra, M. M., Caron, M. G., and Lefkowitz, R. J. (1992) Science 257, 1264-1267) receptors. Beta gamma mediates the membrane targeting of the beta-adrenergic receptor kinase (beta ARK), in response to receptor activation, through a specific beta ARK-beta gamma interaction. This process utilizes the membrane-anchoring properties of the isoprenylated gamma subunit of beta gamma. In the present study, we have employed three distinct approaches to identify the region within the carboxyl terminus of beta ARK which binds beta gamma and thereby results in membrane translocation. We studied the ability of beta gamma to enhance the enzymatic activity of a series of truncated mutants of bovine beta ARK1, the ability of glutathione S-transferase fusion proteins containing various lengths of the carboxyl terminus of beta ARK to bind beta gamma subunits, and the ability of synthetic peptides comprised of beta ARK sequences to inhibit beta gamma activation of beta ARK1. We find that the minimal beta gamma binding domain of beta ARK is localized to a 125-amino acid residue stretch, the distal end of which is located 19 residues from the carboxyl terminus. A single 28-mer peptide (Trp643 to Ser670) derived from this sequence effectively inhibited beta gamma activation of beta ARK1, with an IC50 of 76 microM. The identification of this "beta gamma binding domain" on beta ARK and the development of peptide inhibitors provide important tools for the study of G protein-coupled receptor desensitization, as well as for the investigation of beta gamma activation of other G protein-effector systems. PMID- 8463336 TI - Effects of adenine tracts on the B-Z transition. Fine tuning of DNA conformational transition processes. AB - The effects exerted by short runs of adenines (A-tracts), alternating (AT)n segments, and single-stranded DNA upon the right- to left-handed DNA transition, as well as upon the energetic and structural parameters of the B/Z junctions, were investigated by using synthetic segments in which these motifs are coupled to a potentially Z-forming core. UV, CD, and 31P NMR studies of the salt-induced B to Z transition occurring in the various segments indicate that the transition is composed of two phases: a slow rate-determining induction of an initial structural deformation followed by a cooperative propagation of this "nucleus" in the form of a left-handed Z-DNA. The first phase is found to be crucially affected by the nature of the sequences coupled to the potentially Z-forming core. Thus, a higher rigidity of the flanking segments, such as that characterizing adenine tracts, is associated with higher energy values required for the induction of the initial conformational deformation, as well as with more defined structural parameters of the ultimate B/Z junctions. The second phase is affected mainly by the composition and sequence of the Z-forming segment. The observations that DNA conformational changes can be finely tuned and modulated by parameters pertaining to both the segment which undergoes the transition and the flanking sequences support the notion that DNA secondary motifs, such as the Z form and A-tracts, might be involved in the regulation of cellular processes. PMID- 8463337 TI - Cellular retinol-binding proteins are determinants of retinol uptake and metabolism in stably transfected Caco-2 cells. AB - The mammalian small intestine contains two related cellular retinol-binding proteins, CRBP and CRBP II, which are thought to have distinct functions. The human intestinal cell line, Caco-2, was used as a model system for testing the hypothesis that intracellular levels of these proteins directly modulate the absorption and subsequent metabolism of retinol in enterocytes. Immunoblot and Northern blot hybridization demonstrated that Caco-2 cells express CRBP II and cellular retinoic acid-binding protein I in increasing amounts as the cells become more differentiated but do not express detectable quantities of CRBP. Stably transfected cloned Caco-2 cell lines that over-express CRBP II or coexpress CRBP and CRBP II and a control cell line that contains the expression vector without an insert were established. Retinol uptake and retinyl ester synthesis were increased up to 2-fold by coexpression of CRBP or over-expression of CRBP II. No significant differences were detected in the pattern of retinyl esters synthesized from exogenous [3H]retinol. This suggests that the fatty acid pools utilized for retinol esterification were the same despite differences in the CRBP and CRBP II phenotype of the cell lines. There were no differences between apical and basolateral [3H]retinol uptake or metabolism for filter grown transfected or wild type cell monolayers. Thus, neither CRBP II nor CRBP appear to preferentially interact with luminal- or plasma-derived retinol. Notably, in a cell line which over-expressed CRBP, endogenous CRBP II was reduced by 5-10-fold compared with the wild type and control cell lines. These studies indicate that CRBP and CRBP II levels are determinants of intracellular retinol accumulation and esterification, and they suggest that CRBP-bound retinol or a metabolite can regulate the expression of CRBP II in the mammalian intestine. PMID- 8463338 TI - On the mechanism of the activation of human plasminogen by recombinant staphylokinase. AB - The mechanism of activation of human plasminogen by recombinant staphylokinase (STAR) was studied using the active site titrant p-nitrophenyl-p' guanidinobenzoate (NPGB). NPGB prevented active site exposure in equimolar mixtures of plasminogen and STAR but reacted stoichiometrically with mixtures preincubated in the absence of titrant. Active site generation occurred progressively, with a marked initial lag phase followed by an exponential growth phase, and was associated with the conversion of single-chain plasminogen to two chain plasmin. Incubation of mixtures of plasminogen and STAR with catalytic amounts (< 0.2% molar ratio) of preformed plasmin.STAR complex or of urokinase shortened the lag hase, whereas catalytic amounts (5% molar ratio) of the plasmin inhibitor alpha 2-antiplasmin delayed active site generation. The following kinetic model for the activation of plasminogen (P) by STAR (S) fits the experimental data, [formula: see text] and is described by [formula: see text] or [formula: see text] In this model, plasminogen and STAR produce an inactive complex (P.S), in which active plasmin.STAR (p.S) is generated in a rate limiting step, which is accelerated by plasminogen activators and delayed by plasmin inhibitors. At room temperature in a 0.1 M Veronal buffer, pH 8.3, containing 0.1 M arginine, the data are adequately fitted by the integrated equation with k1 = 4.0 x 10(-7) s-1 and k2 = 1.3 x 10(-2) microM-1 s-1. The k1 value could be explained by contamination of the plasminogen preparation with 3 ppm plasmin, converted by S to p.S. It is concluded that STAR activates plasminogen via a mechanism which differs in several essential aspects from that of streptokinase. PMID- 8463339 TI - G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. AB - We investigated the temporal regulation of cyclin A- and B1-dependent kinases in human lymphoma cells treated with nitrogen mustard (HN2) and pentoxifylline, to determine whether the activity of these complexes correlated with cell cycle arrest induced by DNA damage. Cells were synchronized in G1/S, treated with HN2, and then postincubated with pentoxifylline. HN2-induced a protracted delay in G2 phase. This delay correlated with suppression of cyclin B1- and cdc2-kinase activities, and stabilization of hyperphosphorylated-cdc2 in the presence of similar cyclin B1 levels to those found in mitosis. HN2 had no discernible effect on the S phase activity of cyclin A- or cdk2-immune complexes. Entry of control cells into mitosis correlated with destruction of cyclin A, disappearance of cyclin A-bound cdk2 and decreased cdk2 kinase activity. G2 delay induced by HN2 was associated with stabilization of cyclin A, increased abundance of cyclin A bound cdk2, and increased cdk2 activity. Cyclin A was also associated with cdc2, which, contrary to complexes containing cdk2, were only activated upon entry into mitosis. Pentoxifylline abrogated cell cycle arrest induced by aphidicolin and HN2 in human lymphoma cells. Pentoxifylline also reverted the activity of cyclin A- and B1-kinases in HN2-treated cells to approximately that observed in controls. Our findings suggest that delayed entry into mitosis following DNA damage correlates with suppression of cyclin B1/cdc2 and cyclin A/cdc2 complexes, while maintaining cyclin A/cdc2 complexes in an active state. Furthermore, we found that pentoxifylline disrupts the signal transduction pathway that regulates these complexes when damaged DNA is present, resulting in abrogation of cell cycle arrest. PMID- 8463340 TI - Characterization of the promoter-regulatory region and structural organization of E1 alpha gene (BCKDHA) of human branched-chain alpha-keto acid dehydrogenase complex. AB - We have isolated genomic clones containing the complete exon 1 and the promoter regulatory region of the E1 alpha gene (BCKDHA) of human branched-chain alpha keto acid dehydrogenase complex. The cloning was achieved by amplification of a genomic library in the SRB (P2) host strain that allowed the replication of nonstandard DNA structures. The results of this and previous (Dariush, N., Fisher, C. W., Cox, R. P., and Chuang, D. T. (1991) FEBS Lett. 284, 34-38) studies showed that the human E1 alpha gene contains 9 exons, and spans at least 55 kilobases (kb). Exon 1 is 135 bp in length, and contains multiple transcription initiation sites at bases +1, +18, and +22. The complete human E1 alpha cDNA is, therefore, 1,758 bp in length excluding the poly(A)+ tail, and has 27 nucleotides in the 5'-untranslated region. Sequencing of the 5'-flanking region disclosed the absence of a canonical TATA-box in the vicinity of base -30. Several sets of "CAAT" box-like sequences and Sp1 binding-sites are present. Also present are copies of potential AP-2 binding, fat-specific element 1, fat specific element 2, glucocorticoid-responsive element, and cAMP-responsive element sequences, as well as multiple sets of direct and inverted repeats. The promoter-regulatory region was characterized using deletion constructs and the luciferase reporter assay. The human hepatoma cells (Hep-G2) and Chinese hamster ovary (CHO) cell lines were used as hosts. The results obtained with Hep-G2 cells indicate that the region for high level transcription is located between bases 320 and -115. Extension of the 5'-end of the insert to beyond base -320 markedly reduces promoter activity. The results strongly suggest the presence of inhibitory elements in the region upstream of base -320. Assays in CHO cells show that the region for high level transcription lies between bases -909 and -115. The variation in the region for high level transcription in Hep-G2 and CHO cells may represent cell-type specific differences in the E1 alpha gene promoter function. PMID- 8463341 TI - Analysis of heat shock element recognition by saturation mutagenesis of the human HSP70.1 gene promoter. AB - We analyzed the human HSP70.1 gene promoter heat shock element by saturation point mutagenesis and performed quantitative assays of in vitro heat shock factor binding and of in vivo transcription activity in HeLa cells with this extensive set of mutants. These results showed a significant correlation between measurements of heat shock factor binding and heat-inducible expression and provided a detailed thermodynamic description of the preferred recognition consensus sequence. In particular, this work demonstrated that outer positions 1 and 5 of the 5-base pair motif NGAAN, in addition to the most conserved triplet in the center, can have a strong influence on activity. Optimal activity occurred with the sequence AGAAC, and the levels of activity for all single base substitution variants were established. This analysis should be useful both for predicting the activity of potential heat shock element sequences near mammalian promoters and for interpreting structural features of protein-nucleic acid interactions in this system. PMID- 8463342 TI - Cytochrome P-450 55A1 (P-450dNIR) acts as nitric oxide reductase employing NADH as the direct electron donor. AB - Cytochrome P-450dNIR (P-450dNIR), involved in the fungal denitrification by Fusarium oxysporum, was purified to homogeneity. The cytochrome P-450 (P-450) exhibited a potent nitric oxide (NO) reductase activity to form nitrous oxide (N2O) employing NADH but not NADPH as the sole effective electron donor. The apparent maximum turnover rate against NO was estimated as high as 31,500 min-1. The stoichiometry of the reaction between NO:NADH:N2O was 2:1:1. The reaction required neither an artificial electron-carrying mediator nor other proteinaceous components. An anaerobic incubation of ferric P-450dNIR.NO complex, but not of free ferric P-450dNIR, resulted in rapid reduction of the P-450, indicating that P-450dNIR.NO complex was reduced directly by NADH. Spectral changes during catalytic turnover indicated that decomposition of the ferrous P-450.NO complex might be rate-limiting. The reaction was not inhibited by carbon monoxide at all, suggesting that the free ferrous P-450 is not formed during turnover. On the basis of these results a possible reaction mechanism was considered. The present results demonstrated not only the unique reaction catalyzed by P-450, but also the first P-450-dependent reaction where the electron transport from NAD(P)H to P 450 is not supported by other components. Now that the physiological function of P-450 55A1 (P-450dNIR) has been found, we propose to alter the trivial name to P 450nor. PMID- 8463343 TI - Recombinant laminin G domain mediates myoblast adhesion and heparin binding. AB - A recombinant mouse cDNA fragment encoding the G domain of the basement membrane laminin A chain was inserted into the eukaryotic baculovirus expression vector pVL1392 modified to produce fusion proteins carrying the rat fibronectin signal. G domain, expressed and secreted as a soluble glycoprotein (rG), was purified to near homogeneity without denaturing conditions. By electron microscopy rG possessed the same globular morphology as found in laminin. rG was cleaved with elastase into two fragments, rG70 and rG50. The latter fragment possessed the identical N terminus as laminin fragment E3 and both shared the same secondary structure by circular dichroism. rG, and rG containing a deletion (residues 2980 3028) rich in basic residues bound to heparin with similar avidity. rG also promoted mouse C2 myoblast cell adhesion and spreading, and evaluation of myoblasts on rG70 and rG50 further revealed that cell spreading was an activity confined to the more proximal sequence of rG70. Antibody specific for rG70 completely blocked cell adhesion to intact laminin in contrast to antibody specific for E3. Finally rG did not inhibit laminin polymerization. These data support the role of G domain in cell and heparin binding, but not laminin self assembly, and the approach provides a means to further characterize these functions. PMID- 8463344 TI - Regulation of tissue-specific splicing of the calcitonin/calcitonin gene-related peptide gene by RNA-binding proteins. AB - Transcripts of the rat calcitonin/calcitonin gene-related peptide (CGRP) gene are alternatively spliced in a tissue-specific manner resulting in the production of calcitonin mRNA and peptide in thyroid C cells and CGRP mRNA and peptide in neurons. Transfection studies using calcitonin and chimaeric human beta globin/calcitonin exon minigene constructs showed that the splice acceptor and exon specific to calcitonin mRNA are spliced much less efficiently in CGRP producing cells (F9 teratocarcinomas) than in cells that preferentially make calcitonin (HeLa cells). In vitro splicing of chimaeric human beta globin/calcitonin transcripts in HeLa nuclear extracts were inhibited by the addition of nuclear extract from CGRP-favoring cells or tissues such as rat brain. This inhibition was specific as splicing of human beta-globin first intron transcripts was not affected by comparable amounts of rat brain extract. Fractionation of rat brain nuclear extracts allowed the partial purification of two brain-specific polypeptides of apparent molecular mass of 43 and 41 kDa which preferentially bind RNA containing the calcitonin-specific splice acceptor. Since these polypeptides cofractionate with the calcitonin mRNA-specific splicing inhibition activity, we suggest that they may mediate the inhibition of splicing observed in vitro and underlie, in part, the inefficient calcitonin mRNA production observed in CGRP-favoring cells in vivo. PMID- 8463345 TI - Expression of human platelet glycoprotein Ib alpha in transgenic mice. AB - Platelets are cytoplasmic fragments of megakaryocytes and, therefore, their membrane proteins cannot be manipulated by expression methods in culture. To overcome this limitation, we have expressed human glycoprotein (GP) Ib alpha in transgenic mouse megakaryocytes and found that it was present on the surface of platelets associated with the mouse GP Ib beta subunit. This finding demonstrates that assembly of the heterooligomeric GP Ib complex occurs through mechanisms conserved across species. In contrast, the receptor function of GP Ib exhibited restricted species specificity, since only the chimeric complex containing human GP Ib alpha bound human von Willebrand factor and supported platelet aggregation mediated by ristocetin. These studies demonstrate the transgenic engineering of a platelet adhesion receptor under control of the human GP Ib alpha promoter and illustrate a new approach to manipulate platelet receptors and study structure function relationships in hemostasis and thrombosis. PMID- 8463346 TI - Tissue reaction to alumina implants inserted into the tibiae of rats. AB - We examined the tissue reaction to three alumina implants--single-crystal alumina (SA), dense polycrystal alumina (DPA), and porous polycrystal alumina (PPA)- inserted transcortically, extending into the medullary canal of rat tibiae, and assessed the quantitative differences in bone reaction using an image processing system. There was no difference in the degree of maturation of newly formed bone around the three kinds of alumina. SA and DPA were encapsulated with a continuous bone layer, but some bone tissue was attached focally around PPA. Bone trabeculae in the control site diminished in size and number chronologically. Multinucleated giant cells were observed on the surface of DPA and PPA, but not on SA. Tabulation of the quantitative evaluation indicated that SA showed the highest, DPA a lower, and PPA the lowest in bone contact rate, bone contact thickness, and bone contact area. These data suggest that SA is superior to the other two as an implant material. PMID- 8463347 TI - Guided bone tissue elaboration by osteogenic cells in vitro. AB - Primary rat bone marrow cells were cultured for 2 weeks in polystyrene dishes whose surfaces had been roughened using 600- or 320-grit silicon carbide paper. Eight samples were prepared of each of the three groups of dishes, to include a nontreated control surface. Following the culture period, the dishes were stained by von Kossa's method. The distribution of bone formed during the culture period was examined by light microscopy and the area of bone formed quantified. Results demonstrated that both the amount and spatial distribution of bone were influenced by the roughness of the underlying substratum. Differences between the smooth and roughened surfaces were statistically different at P < .05. PMID- 8463348 TI - Plasma protein adsorption to hemodialysis membranes: studies in an in vitro model. AB - Upon interaction of whole blood with foreign materials, heterogeneous protein films are deposited onto the artificial surface (eg, hemodialysis membranes). The composition of these protein films subsequently affects various processes, eg, thrombogenesis or activation of the complement system. We developed an in vitro model with which we can identify and study proteins interacting with capillaries during hemodialysis. Using this model we studied the cuprophane dialyzer GFS 120 (CP) and the polymethylmetacrylate membrane Filtryzer B2-1.2 (PMMA). Heparinized whole blood from healthy young volunteers was dialyzed on an extracorporeal dialysis machine. After the dialysis procedure the adsorbed material was eluted from the hemodialysis membranes by different eluants and subsequently analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. A number of proteins could be identified in the eluates of both membrane types. Interestingly, platelet glycoproteins could only be found in PMMA eluates. Albumin, IgG, and antithrombin III were mainly present in the cuprophane eluates. Fibrinogen was demonstrable in all eluates, but in relatively low amounts, and the protein was significantly degraded. Degradation products of antithrombin III and complement factor 3 could also be identified. The process causing the degradation has not yet been identified, but may be due to proteases released from damaged cells. PMID- 8463349 TI - Attachment and proliferation of bovine aortic endothelial cells onto additive modified poly(ether urethane ureas). AB - To better understand endothelial cell interactions with poly(ether urethane urea) (PEUU) materials, and to assess bovine aortic endothelial cell attachment, films were incubated for 24 h with BAEC in media containing 5% fetal bovine serum. Other films were allowed to incubate for 4 more days in media containing 5% fetal bovine serum without cells to assess BAEC proliferation. The assay was performed on PEUU films modified with acrylate and methacrylate polymer and copolymer additives that spanned a wide range on the hydrophobicity/hydrophilicity scale. Tissue culture polystyrene (TCPS) was used as a control. The assay showed that PEUU films loaded with Methacrol 2138F [copoly(diisopropylaminoethyl methacrylate [DI-PAM]/decyl methacrylate [DM]) (3/1)] or with its hydrophilic component, DIPAM, in homopolymer form (i.e., h-DIPAM), significantly enhanced BAEC attachment (approximately 80% of TCPS values) and proliferation (approximately 80%) when compared to unloaded PEUU films (attachment 73%; proliferation, 47%) or to PEUU films loaded with the more hydrophobic acrylate or methacrylate polymer additives (attachment, 32-69%; proliferation, 18-57%). The assay also showed that PEUU films coated with homopoly(diisopropylaminoethyl acrylate) (h-DIPAA) significantly enhanced BAEC attachment and proliferation when compared to PEUU films coated with h-decyl acrylate (h-DA); films coated with the copolymer of these two acrylates (i.e., co-[DIPAA/DA] [3/1]) showed intermediate behavior. To explain the enhancement of BAEC interaction with films loaded with Methacrol 2138F or h-DIPAM, when compared to unmodified PEUU films or to PEUU films loaded with more hydrophobic acrylate and methacrylate polymer additives, it was assumed that the additives near the surface region of the solvent swollen PEUU matrix may have migrated to, or near to, the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. It is suggested that, once at this surface region, dynamic reorientation in response to an aqueous medium ensured the additives were able significantly to influence protein adsorption, and concomitant endothelial cell behavior, but only if they interacted with aqueous media more favorably than the PEUU. The ability of Methacrol and h-DIPAM additives to enhance endothelial cell behavior is argued to be the result of increased hydrophilicity. This is the result of exposed, hydrogen-bonding DIPAM moieties and increased surface flexibility, which is itself due to the hydration of unhindered Methacrol chains, which may create an additive enriched PEUU-water interfacial zone. PMID- 8463350 TI - Patency and blood flow in gas denucleated arterial prostheses. AB - Biomaterials exposed to blood often fail due to thrombosis. Gas nuclei (air) in the material are thrombogenic and a potential cause of failure. The effects of gas nuclei on patency and blood flow were studied in 4 mm diameter arterial grafts (Gore ePTFE; Johnson and Johnson Vitagraft ePTFE; Bard ACG EXS) in the femoropopliteal position of dogs. Control and denucleated (air-free) grafts were implanted bilaterally. Grafts were denucleated by immersion in degassed saline and exposure to 4 torr vacuum and 3,000-20,000 psig pressure. Graft patency was determined at harvest in 46 dogs. Blood flow was measured with acoustic flow probes in eight dogs. Denucleated graft patency was 60% after 2 days of implant while control patency was 22% (P < .05). Measured blood flow was higher in denucleated grafts than in control grafts (P < .02) in 4 of 5 dogs which had significantly different flows. Patency and flow decreased to zero for both control and denucleated grafts over periods of up to 80 days. Air in the control grafts may have been absorbed within several days, leading to late similarity with the denucleated grafts. Thus, removing the air from 4 mm ePTFE grafts decreased acute thrombosis and increased the patency. PMID- 8463351 TI - Protein adsorption and endothelial cell attachment and proliferation on PAPI based additive modified poly(ether urethane ureas). AB - To better understand vascular interactions with poly(ether urethane urea) (PEUU) materials, protein adsorption, and endothelial cell attachment and proliferation assays were performed on a base PEUU formulation, on PEUU formulations loaded with hydrophobic and amphiphilic poly(methylene-[polyphenyl isocyanate]) (PAPI) based additives, and on PEUU formulations in which some of the polymer chains had been endcapped with either diisopropylaminoethyl (DIPAA) or decyl (DA) moieties. Protein adsorption experiments with PAPI-based additives showed that additive loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Protein adsorption to the DA and DIPAA endcapped PEUU films was found not to vary consistently from that of the unloaded PEUU film. Endothelial cell attachment and proliferation experiments with PAPI-DA and polyethylene glycol-PAPI-DA (PEG-PAPI-DA) loaded PEUU films showed that many of the films exhibited attachment and proliferation that was significantly enhanced compared to PEUU A' and that approached or equaled that of the tissue culture polystyrene control. Experiments with PAPI-DIPAA and PEG-PAPI-DIPAA loaded PEUU films exhibited attachment and proliferation data that was often below 10% of the tissue culture polystyrene control values. Experiments with the DA and DIPAA endcapped PEUU films showed endothelial cell attachment and proliferation that was statistically indistinguishable from the PEUU A' values. Contact angle analysis was carried out on the endcapped PEUU films, on the PAPI based additive loaded PEUU films, and on PEUU A' using the sessile drop method. The advancing and receding contact angle behavior of the PAPI-based additive loaded PEUU films deviated markedly from the behavior of PEUU A', suggesting that the additives were present at the PEUU-water interface. The contact angle behavior of the endcapped PEUUs was similar to that of PEUU A', suggesting that the DA and DIPAA endcap moieties did not exist at the hydrated PEUU surface in appreciable quantities. To explain the differences in protein adsorption and endothelial cell behavior on the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at, or near the PEUU-air interface during film formation, creating an additive enriched PEUU surface region.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463352 TI - Human umbilical vein endothelial cell culture on heparin-like microcarriers. AB - Biospecific functional polymers, i.e., polymers randomly substituted with specific chemical functional groups, were designed to interact with living systems. Interactions between polystyrene sodium sulfonate (PSSO3Na) and insulin secreting RINm5F cells have been previously described. For the sake of comparison, interactions of PSSO3Na with human umbilical vein endothelial cells (HUVEC) were studied. In this case, the interaction is indirect, i.e., mediated by a binding protein, fibronectin (Fn). This was evidenced by HUVEC culture on Fn precoated PSSO3Na microcarriers. The interactions between PSSO3Na and HUVEC result in a biologically normal proliferation of cells and synthesis and secretion of Von Willebrand Factor (VWF). These results show that different biospecific interactions may occur between cells in culture, binding proteins and polymers randomly substituted with suitable functional groups. HUVEC, when cultured on heparin-like microcarriers, behave differently from other cells like RINm5F, whose interaction with the same polymers is not mediated by binding proteins. PMID- 8463353 TI - Toxicity of L-ascorbic acid to L929 fibroblast cultures: relevance to biocompatibility testing of materials for use in wound management. AB - Fibroblast cultures are often used to evaluate materials intended for medical use, cytotoxicity being taken as an indicator of bioincompatibility. Such an approach has previously been taken with ascorbic acid in determining its value in wound healing. We have now reexamined the toxicity of L-ascorbic acid to L929 fibroblast cells in culture. Concentrations of ascorbic acid between 0.5 mM and 11 mM were tested. At concentrations above 2 mM, ascorbic acid was found to inhibit cell proliferation, with cell viability decreasing as the concentration was increased. This effect could be prevented by the addition of either superoxide dismutase or catalase to the culture medium. Assays of glutathione and glutathione disulfide were carried out on 8 day old cultures exposed for 24 h to the same concentrations of ascorbic acid. A dose-related depletion of glutathione occurred whilst glutathione disulfide levels remained essentially constant. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were induced by ascorbic acid at all concentrations tested but the ratio of NADP to NADPH nevertheless increased as the concentration of ascorbic acid increased. Finally, ATP in cells from 8-day-old cultures became depleted in the presence of ascorbic acid at concentrations in excess of about 5 mM when assayed after 24 h incubation. These biochemical changes and the concomitant cytostatic/cytotoxic effects may be ascribed to the reactive oxygen species produced by the autoxidation of ascorbic acid in the culture medium. Ascorbic acid breakdown products appeared not to be directly involved. In addition, our results suggested that superoxide acted cooperatively with hydroxyl to elicit these effects on the fibroblasts. It is evident from this study that the microenvironment surrounding fibroblasts in culture may differ fundamentally from that surrounding fibroblasts in a healing wound, making it impossible to extrapolate directly to an in vivo situation and hence to make any recommendations from these results concerning the use of ascorbic acid in wound healing. PMID- 8463354 TI - Effect of interfacial variables on metal-porcelain bonding. AB - While ceramic-to-metal bonding has been used in many applications, the actual chemical and physical factors leading to optimum bond strength are not well understood. In this work, several variables affecting the bonding between dental porcelain and a palladium alloy (85% Pd, 10% Cu, and 5% Ga) were investigated: 1) precoating the metal by sputtering various oxides before porcelaining; 2) peroxidation of the metal base before porcelaining; 3) porcelaining under reducing atmosphere; and 4) surface roughening at controlled levels before porcelaining. Using a modification of the push doughnut shear bond strength test to measure bond strength the following results were obtained. 1) Compared with standard "control" samples, the aluminum oxide precoated specimens showed a bond strength improvement of 46%, while the copper, manganese, and tin oxide precoatings exhibited smaller effects. 2) Preoxidation of the metal base led to pronounced bond strengthening (152%) by surface roughening as well as oxide formation. 3) Porcelaining under a reducing atmosphere severely reduced bond strength (88% lower than the controls) indicating the role of oxidation during the standard firing cycle. 4) Mechanical roughening of the surface by controlled amounts gave pronounced improvements with greater notch depth. Coarse roughening produced the highest bond strength improvements (486%). PMID- 8463355 TI - Phase studies of a urethane model compound and polyether macroglycols by infrared spectroscopy and the relationship between eutectic composition of soft segment and blood compatibility. AB - The binary mixtures of a urethane model compound, diethyl 4,4'-methylenebis(N phenylcarbamate) (MDU), and various polyether macroglycols have been investigated mainly by infrared (IR) spectroscopy. The mixtures of macroglycol and MDU showed two C=O bands (free C=O at higher wave number, hydrogen bonded C=O at lower wave number), and the intensity of free C=O increased while that of hydrogen bonded C=O decreased linearly with increasing molar ratio of macroglycol/MDU. The slope of the increase or decrease suddenly changed at the specific molar ratio around the eutectic composition. The eutectic molar composition for PTMO1000/MDU was determined as 1.15 or 1.1 by differential scanning calorimetry (DSC) or infrared (IR) studies while that for PTMO3000/MDU as 0.345 or 0.55 by DSC or IR, respectively. The eutectic compositions for other sets were determined by IR studies as follows: PEO1000/MDU, 0.4; PEO3000/MDU, 0.16; PPO1000/MDU, 1.4; PPO3000/MDU, 0.45. The number of ethylene oxide, tetramethylene oxide, and propylene oxide units to form a eutectic with MDU calculated from these values were 15-20, 10-11, and 23-24, respectively. The similar DSC or IR changes were observed in the various kinds of polyurethanes such as MDI/BD, MDI/PTMO/BD, and MDI/PTMO polymers. The relationship between the eutectic compositions of soft segments (MDI/macroglycol) and the ideal Mn of the macroglycols in blood compatibility of segmented polyurethanes are discussed. PMID- 8463356 TI - Evaluation of a relationship between polymer bulk hydroxyl and surface oxygen content and in vitro serum-material interaction. AB - To evaluate serum-material interaction for six types of minimodule and to assess the relationship between the interaction and chemical composition, notably bulk polymer hydroxyl (-OH) percent of polymer, or surface oxygen (SO) percent, polymeric membranes with varying -OH and SO percents were evaluated with normal human serum. The membrane materials (-OH percent and SO percent) evaluated included polypropylene (PP; 0% and 1.9%), polyvinyl alcohol (PVA; 23.7% and 27.3%), ethylene vinyl alcohol (EVAL 4A and D; 30.4% and 25.3%), Cuprophan (CP; 31.5% and 37.4%), and Hemophan (HP; 30.9% and 23.6%), respectively. Data from serum perfusions expressed as percent changes to sham perfusion showed that solute percent decreases were less than 10% in all materials except PVA (10-22%). PVA and CP had higher C3a, C4a, and C5a, and C3a concentration increases, and had larger suppressive effects for all three mitogen-induced mononuclear cell transformation functions (MNCTF) and concanavalin A-induced MNCTF, respectively. PVA had higher SO percent than EVAL and CP was higher than HP, despite PVA and CP having lower or comparable bulk -OH percent to EVAL or HP. The results obtained in the serum material interaction studies related more with the SO percent of the polymer rather than bulk -OH percent. The differences for C4a and PHA-induced MNCTF observed between the two EVAL membranes may be associated with significantly different pore size and therefore different surface structural properties. These results suggest that surface chemical (SO percent on the materials) and structural property analyses are important factors in biocompatibility parameter studies. PMID- 8463357 TI - The interesting patient. PMID- 8463358 TI - Skin lesion in an acutely ill man with HIV. PMID- 8463360 TI - Fatigue and edema in steroid therapy. PMID- 8463359 TI - Diagnosis and management of neurocysticercosis. AB - Long endemic in developing countries, cysticercosis is surfacing in the United States. Diagnosis of CNS involvement has been aided by laboratory and radiologic advances. Anthelmintic agents add to treatment options. PMID- 8463361 TI - Drug-induced renal disease. AB - Many pharmacologic agents affect the kidney, but special attention should be paid to four classes: aminoglycoside antibiotics, radiocontrast agents, ACE inhibitors, and NSAIDs. Iatrogenic complications associated with these agents include acute renal failure, acute interstitial nephritis, and prerenal failure, which are frequently reversible with early diagnosis. PMID- 8463362 TI - The kindly Dr. Guillotin. PMID- 8463363 TI - A prescription for national health care reform. AB - Insurance systems for controlling costs--quality assurance, preadmission clearance, length-of-stay control--actually add to costs, and also subtract from the quality of patient care. Step one: Eliminate those systems. PMID- 8463364 TI - Syncope, wide mediastinum, and pericardial effusion. PMID- 8463365 TI - Current understanding of Lyme disease. AB - It is now the most common vector-borne disease in the United States. But because of misdiagnosis, the spread of this disease may also be more apparent than real. Lack of standardized serologic tests and varying clinical presentations do create confusion. Nevertheless, it is possible to distinguish Lyme disease from look alike disorders, such as chronic fatigue syndrome and fibromyalgia. PMID- 8463366 TI - Cytokines and cancer cachexia. AB - A by-product of cancer (and of other chronic diseases or severe trauma), cachexia appears to be mediated by various cytokines. The first to be identified--tumor necrosis factor--may be a principal mediator. With molecular cloning techniques, future treatment strategies could include blockade of TNF activity using highly specific reagents. PMID- 8463367 TI - Back pain in the elderly patient. PMID- 8463368 TI - Annotation: autism, executive functions and theory of mind: a neuropsychological perspective. PMID- 8463369 TI - Mental development in late infancy after prenatal exposure to benzodiazepines--a prospective study. AB - Seventeen infants born to mothers who used benzodiazepines (BZD) throughout pregnancy were followed prospectively and compared with 29 infants born to mothers who had not used psychoactive substances. On the Griffiths' Developmental Scale, the BZD-exposed infants demonstrated consistently lower mean GQs and DQs for all subscales at 5, 10 and 18 months of age. The differences in GQ reached statistical significance at 10 and 18 months. The DQs differed significantly for all subscales at 10 months and for the personal-social behaviour and hearing and speech subscales at 18 months of age. We suggest that prenatal exposure to BZD may cause a general delay in mental development up to 18 months of age. PMID- 8463370 TI - A cross-national prevalence study of children with emotional and behavioural problems--a WHO collaborative study in the Western Pacific Region. AB - Emotional and behavioural problems in primary school children were investigated with Rutter's questionnaires, in Japan (N = 2638), China (N = 2432) and Korea (N = 1975). The prevalence rates of children with deviant scores on the teachers' and parents' scales were 3.9 and 12.0% in Japan, 8.3 and 7.0% in China and 14.1 and 19.1% in Korea, respectively. Deviance of the antisocial type was more frequent than the neurotic type in Japan and China. Both types were almost equally frequent in Korea. The prevalence of deviance was higher in boys, and also higher in those children with poor school achievement. In China and Korea, the prevalence was higher in children from one-parent families. Although other family background factors had major effects on deviant behaviour in these two countries, the number of siblings and birth order had only a limited effect on the deviant behaviour of children in Japan, China and Korea. PMID- 8463371 TI - Psychiatric disorders in Japanese secondary school children. AB - Approximately 2000 ordinary secondary school children were investigated using screening methods such as the Rutter teacher's and parent's questionnaires and a diagnostic interview. The prevalence estimate was 16% for the 12-13-year-olds and 14% for the 14-15-year-old children. Disorders were identified in boys more often than in girls (boys: girls = 2.4:1, as the ratio of prevalence estimates). Emotional disorders were equally common in boys and girls. However, conduct disorders were found more frequently in boys (boys: girls = 7:1). Out of the children who were judged as having psychiatric disorders only one had received any professional help except from that given by teachers, regardless of severity. PMID- 8463372 TI - Behaviour and emotional problems in three-year-old children of Asian parentage. AB - Three-year-old Asian children in inner Birmingham were found to have a similar prevalence of behaviour and emotional disturbance to white English children. The Asian children had fewer sleep problems than the white and their mothers had less difficulty in controlling them. There was a difference in parental attitude to difficult behaviour between the two groups and also several differences in associated social variables. In both groups there was a high level of psychological distress in the mothers of the children with behaviour problems and to a lesser extent the fathers. Implications for service provision are discussed. PMID- 8463373 TI - Pride and mastery in children with autism. AB - The goal of this study was to compare expressions of pride and mastery in samples of preschool autistic, mentally retarded and normal children. A paradigm was used in which children completed developmentally appropriate puzzles, both with and without praise. Results indicated that compared to the other children, as many autistic children smiled upon completion of the task, but many fewer looked up to share their pleasure with the parent or experimenter or drew attention to the task. Moreover, significantly more autistic children showed avoidant responses, particularly in response to praise. These findings are discussed in terms of theoretical issues regarding the development of pride and mastery in children with significant social deficiencies. PMID- 8463374 TI - The Family System Test: differences in perception of family structures between nonclinical and clinical children. AB - Nonclinical respondents and psychiatric outpatients (N = 400) between the first and twelfth grades portrayed their families as they perceived them in typical and in conflict situations using the Family System Test (FAST), a figure placement technique that focuses on cohesion and hierarchy in the family. Results showed that typical representations were influenced by whether a respondent was a patient or not, but not by the type of mental disorder. Clinical respondents were less likely to represent their families as being either cohesive, moderately hierarchical or as having clear generational boundaries. In conflict representations, both clinical and nonclinical respondents indicated low cohesion in family patterns. Results were interpreted from a family systems approach as well as from a clinical perspective. PMID- 8463375 TI - The emotional impact of frightening stories on children. AB - This study of the impact of fairy tales examined catharsis vs repetition compulsion hypotheses. Children with high- or low-trait anxiety, aged 6-9 (n = 132), listened either to a frightening story, a frightening-happy end story, a pause story (for measuring anxiety), or a neutral story. They were tested for state anxiety before and afterwards and their preference for a second hearing was evaluated. The procedure was repeated after three weeks. The findings show an increase in anxiety following the frightening story only. Preference and state anxiety correlated positively in the frightening story (repetition compulsion) and negatively in the pause story (catharsis). It was concluded that anxiety is elicited by the frightening elements of the story, rather than the unconscious symbolic content. PMID- 8463376 TI - The behaviour of 3-year-old children: prevalence and parental perception of problem behaviour: a research note. AB - A rating of parental concern was added to the Behaviour Checklist (BCL), which was then used as part of a Health Visitor administered routine developmental assessment of 1170, 3-year-old children. The overall prevalence of behaviour problems using a cut-off score of 10 was 10%, with 66% of parents having one or more concerns about their child. There were no sex differences. Parents of only children had more concerns on 6 of the 19 items even though their children behaved no differently from those with siblings. The usefulness of the BCL as a routine screening measure and the need to identify and address parental concerns at an early stage is discussed. PMID- 8463377 TI - Protein sorting by high-performance liquid chromatography. I. Biomimetic interaction chromatography of recombinant human deoxyribonuclease I on polyionic stationary phases. AB - Chromatographic separations can be tailored to exploit specific interactions between a stationary phase ligand and a protein structural feature of interest. Variations in this feature then form the basis for sorting a mixture of closely related proteins into defined subpopulations. This report describes the sorting of variants of recombinant human deoxyribonuclease I (rhDNase) that differ in the occurrence of deamidation at a single residue. rhDNase, an enzyme that non specifically hydrolyzes DNA, is glycosylated and exhibits considerable charge heterogeneity owing to the sialylation and phosphorylation of its N-linked oligosaccharides. This heterogeneity obscures the relatively subtle differences between deamidated and intact rhDNase, preventing separation on this basis in conventional ion-exchange HPLC. Published structural information on bovine DNase reveals that the analogous labile asparagine residue is involved in DNA binding, so stationary phases containing polyanionic ligands mimicking nucleic acids were employed to separate the deamidation variants of rhDNase. Electrostatically immobilized DNA, a "tentacle" cation exchanger (TCX) and immobilized heparin columns all resolved the deamidated and intact forms of rhDNase when operated at pH 4.5. The ligands of the TCX and heparin columns are sufficiently long, flexible and polyanionic to interact with rhDNase in a manner similar to DNA and to sort rhDNase variants on the basis of the charge difference of a single residue involved in that interaction. A non-hydrolyzable double-stranded oligonucleotide analogue of DNA was also synthesized and immobilized to an HPLC support. This column, operated at pH 6, where rhDNase is active, resolved the two isomeric products of deamidation of rhDNase, i.e., variants of the enzyme containing either aspartate or isoaspartate in lieu of asparagine at the deamidation site in rhDNase. This is the first reported separation of intact variants of a glycoprotein differing on the basis of these isomeric products of deamidation through the common cyclic imide mechanism. PMID- 8463378 TI - UV red fluorescence of Eubacterium lentum. AB - Twenty-nine clinical isolates of Eubacterium lentum and two type species were evaluated for the ability to fluoresce under UV light. Twenty-one of the 29 isolates and both of the reference strains showed orange-to-red fluorescence. This fluorescence did not require blood or hemin in the culture media and did not fade upon air exposure. The fluorescent pigment, after extraction by 1 N NaOH, showed peak excitation at a wavelength of around 400 nm. The capacity of E. lentum to produce fluorescence may be a useful and time-sparing laboratory aid for its identification. PMID- 8463379 TI - Cellular fatty acid compositions of "Achromobacter groups B and E". AB - Strains of "Achromobacter groups B and E" were examined for cellular fatty acid (CFA) composition to evaluate their chemical relatedness to known bacterial species and groups. The CFAs were liberated from whole cells by base hydrolysis, methylated, and analyzed by capillary gas-liquid chromatography. The CFA profiles of the two groups were identical and were distinct from CFA profiles of all other bacteria we have previously tested. These data provide support for results from whole-cell protein pattern analysis and DNA-DNA and rRNA-DNA hybridization studies, which show that "Achromobacter groups B and E" are biotypes of a single new genus and species. PMID- 8463380 TI - Rapid and highly reproducible method for antifungal susceptibility testing of Aspergillus species. AB - A new method for determining the MICs for Aspergillus species with slant-shaking incubation is described. The method was rapid (24 h), produced sharp visual end points, and showed high reproducibility. Additionally, MICs measured by this method correlated well with, as well as were two- to sixfold lower than, those by a reference method. PMID- 8463381 TI - Comparison of the Seradyn Color Vue passive agglutination test and complement fixation for detection of Mycoplasma pneumoniae antibodies. AB - We compared traditional complement fixation (CF) with a new passive agglutination method, the Seradyn Color Vue (SCV) test (Seradyn, Indianapolis, Ind.), for detection of Mycoplasma pneumoniae antibodies in 170 stored serum samples. The SCV test was 90% sensitive in identifying as positive 27 of 30 CF high-titer (> or = 1:64) serum samples and 100% specific in identifying as negative 134 of 134 CF low-titer (< or = 1:32) or negative (< 1:8) serum samples. The SCV test was technically undemanding, and it required no expensive equipment. PMID- 8463382 TI - Detection of Trichomonas vaginalis in pregnant women with the InPouch TV culture system. AB - Trichomonas vaginalis causes a common genitourinary infection which is frequently asymptomatic. At present, pregnant women are not usually screened for the infection unless they are symptomatic. In the present study, we screened and obtained samples for culture from all pregnant women attending a prenatal clinic with the InPouch TV culture system and compared results with those of standard culture in Diamond's medium and slide wet mount examination. The InPouch TV culture system was as reliable as Diamond's medium in detecting T. vaginalis and may be useful and effective in a pregnancy clinic setting. PMID- 8463383 TI - Detection of Mycobacterium tuberculosis DNA in clinical samples by using a simple lysis method and polymerase chain reaction. AB - We have evaluated the polymerase chain reaction for detection of Mycobacterium tuberculosis in clinical samples from patients with tuberculous infection. Two simple methods for mycobacterial DNA release have been compared: sonication and lysis with nonionic detergents and proteinase K. The more effective method was the enzymatic technique. By using this protocol with 75 specimens we detected M. tuberculosis DNA in all of the samples, whereas only 48 and 71 samples were positive by acid-fast staining and culture, respectively. PMID- 8463384 TI - The resurgence of tuberculosis: is your laboratory ready? PMID- 8463385 TI - Current practices in mycobacteriology: results of a survey of state public health laboratories. AB - Fifty-six state and territorial public health laboratories were surveyed to determine whether currently available rapid methods for the identification and drug susceptibility testing of Mycobacterium tuberculosis were being performed. Forty (71%) laboratories use fluorochrome rather than conventional basic fuchsin stains for screening clinical specimens for acid-fast bacilli. Of the 55 laboratories that routinely culture for mycobacteria, 16 (29%) use the more rapid radiometric methods. Species identification of isolates is done by biochemical tests in 13 (23%) laboratories; 40 (72%) use nucleic acid probes, high performance liquid chromatography, or the BACTEC p-nitro-alpha-acetylamino-beta hydroxypropiophenone (NAP) test (rapid tests); 3 laboratories do not perform species identification. Drug susceptibility testing is performed with solid media by 36 of 45 (80%) laboratories, while the more rapid radiometric methods are used by 9 (20%) laboratories. Compared with the laboratories that use conventional methods, laboratories that use rapid methods report results more quickly: for species identification, 43 days (conventional) versus 22 days (rapid); for drug susceptibility testing, 44 days (conventional) versus 31 days (rapid) from specimen processing. Rapid technologies for microscopy and species identification are being used by many, but not all, state and territorial public health laboratories; however, most laboratories do not use the more rapid radiometric methods for routine culture or drug susceptibility testing of mycobacteria. Implementation of such rapid technologies can shorten turnaround times for the laboratory diagnosis of tuberculosis and recognition of drug resistance. PMID- 8463386 TI - Progress toward a simplified polymerase chain reaction and its application to diagnosis of tuberculosis. AB - The complexity, expense, and susceptibility to contamination of the polymerase chain reaction (PCR) are all issues which need to be overcome if PCR is to be used outside of research laboratories. We addressed these problems with respect to the diagnosis of tuberculosis. First, we simplified the procedure for extracting Mycobacterium tuberculosis DNA from sputum samples. Two methods of sample preparation were compared: the chaotrope-silica method and a novel, more simple chloroform method. Second, we developed a colorimetric method for product detection. This method was as sensitive and specific as agarose gel electrophoresis for detection of PCR product. By using a one-tube nested protocol, 5 to 50 genome equivalents of M. tuberculosis DNA were detected. The simplified colorimetric PCR was compared with microscopy and culture for detection of M. tuberculosis in clinical specimens of sputum. A total of 171 sputum samples were investigated from 108 patients, 12 of whom were subsequently found to have tuberculosis by culture and/or microscopy. PCR of samples prepared by the chaotrope-silica method had a sensitivity of 75% and a specificity of 100% whereas PCR of samples prepared by the chloroform method had a sensitivity of 92% and a specificity of 99% when compared with the sensitivities and specificities of the combined classical microbiological methods for the diagnosis of tuberculosis. The simplified colorimetric PCR in combination with the chloroform sample preparation method was at least as sensitive as microscopy but had a greater specificity because samples with atypical mycobacteria were not detected by PCR. The sensitivity of the method for detection of smear-negative and extrapulmonary tuberculosis remains to be investigated. PMID- 8463387 TI - Detection of Helicobacter pylori in dental plaque by reverse transcription polymerase chain reaction. AB - To investigate whether the oral cavity is a potential reservoir and possible sanctuary for Helicobacter pylori, supragingival and subgingival plaques were analyzed by a Helicobacter genus-specific reverse transcriptase-polymerase chain reaction based on the sequence data of H. pylori 16S rRNA. The amplified 500-bp DNA fragment was identified by ethidium bromide staining after agarose gel electrophoresis and by Southern hybridization. Twenty-five dyspeptic patients were studied. Histologic examination of gastric biopsy specimens revealed that 18 had H. pylori gastritis and 7 did not. For seven of the 18 (38.8%) patients with proven H. pylori gastritis, H. pylori was also identified in their dental plaque. None of the patients without H. pylori gastritis had H. pylori in their dental plaque. The detection of H. pylori in dental plaque suggests that this H. pylori colonization is not restricted to the gastric mucosa and that this ecological niche may serve as a possible sanctuary which may be responsible for reinoculation of the stomach after topical anti-H. pylori therapies such as bismuth. PMID- 8463388 TI - Comparison of the BacT/Alert pediatric blood culture system, Pedi-BacT, with conventional culture using the 20-milliliter Becton-Dickinson supplemented peptone broth tube. AB - The performance of the Pedi-BacT system, the BacT/Alert (Organon Teknika Corp., Durham, N.C.) pediatric blood culture bottle, was compared with that of a conventional 20-ml supplemented peptone broth tube (Becton-Dickinson Corp., Cockeysville, Md.) (BD system) in matched aerobic cultures. The tubes of the BD system were visually examined daily for 7 days and were subcultured during the first 24 h of incubation. Pedi-BacT cultures were mechanically agitated and continuously monitored for growth by the instrument. Of the 6,628 compliant pairs, 331 (5.0%) were positive in both systems, 220 (3.3%) were positive in the Pedi-BacT system only, and 170 (2.6%) were positive in the BD system only. One (0.02%) false-negative culture and 15 (0.2%) false-positive cultures occurred with the Pedi-BacT system while 20 (0.3%) false-negative cultures and 35 (0.5%) false-positive cultures occurred with the BD system. Of 288 clinically significant organisms detected in matched pairs from which a single isolate was recovered, 176 (61%) were recovered from both systems, 83 (29%) were recovered from the Pedi-BacT system only (P < 0.0001), and 29 (10%) were recovered from the BD system only. Members of the family Enterobacteriaceae (P < 0.01), miscellaneous nonfermenters (P < 0.05), and Candida spp. (P < 0.01) were isolated more frequently in the Pedi-BacT system than in the BD system. No significant difference in recovery of other organisms was found between the systems. The average time to detection for the Pedi-BacT system ranged from 11.5 h for streptococci to 29.7 h for enterococci, while that for the BD system ranged from 20.3 h for streptococci to 66.4 h for some nonfermenters. The BacT/Alert system is a reliable, labor-saving alternative to conventional blood culture methods. PMID- 8463389 TI - Comparison of phage typing and DNA fingerprinting by polymerase chain reaction for discrimination of methicillin-resistant Staphylococcus aureus strains. AB - A typing procedure for methicillin-resistant Staphylococcus aureus (MRSA) based on the polymerase chain reaction (PCR) amplification of both mecA sequences and variable DNA sequences as present in the prokaryotic genome has been developed. Two primers based on the sequences of DNA repeats as discovered in gram-negative members of the family Enterobacteriaceae allow detection of variable regions in the genome of a gram-positive bacterium such as S. aureus, as does a newly described arbitrary primer. This procedure, enabling the detection of 23 different genotypes in a collection of 48 MRSA isolates, was validated by comparisons with phage typing studies. It appeared that within the same group of isolates only 13 different phagovars could be identified. Combination of the results from both phage typing and genotyping allowed the discrimination of 34 of 48 isolates. However, depending on the primer-variable complexity of the PCR fingerprints, which could also be modulated by combination of PCR primers, clear homologies between the groups defined by either phage typing or fingerprinting were observed. An analysis of an MRSA outbreak in a geriatric institution showed a collection of genetically homogeneous isolates. In agreement with phage typing, PCR fingerprinting revealed the identical natures of the MRSA strains isolated from all patients. PMID- 8463390 TI - Role of beta-hemolytic group C streptococci in pharyngitis: incidence and biochemical characteristics of Streptococcus equisimilis and Streptococcus anginosus in patients and healthy controls. AB - The biochemical characteristics and the isolation rates of the two Lancefield group C streptococcal species (S. equisimilis and S. anginosus) from patients with pharyngitis and asymptomatic controls were compared. Some 239 strains of beta-hemolytic group C streptococci were isolated from 1,480 patients (209 strains) with pharyngitis and 227 controls (30 strains). A total of 44 strains displayed broad hemolysis, were Voges-Proskauer test negative, and produced glucuronidase. Some 72.7% of these strains also fermented ribose. A second group of 159 strains was Voges-Proskauer test positive and glucuronidase negative; 98.8% also displayed minute hemolysis and only 3.7% fermented ribose. These two groups represent typical large-colony S. equisimilis and small-colony S. anginosus, respectively. A small number of strains (36 in total) exhibited intermediate characteristics; morphologically, all 36 strains resembled S. anginosus, but 6 strains biochemically resembled S. equisimilis. No strains of S. equisimilis fermented sorbitol (unlike S. zooepidemicus) and all fermented trehalose (unlike S. equi). The structural carbohydrate profiles of S. equisimilis and S. anginosus both included galactosamine (consistent with their being group C organisms), but the profiles were not distinguishable. In total, 78.5% of strains from controls and 83.3% of strains from patients were determined to be the species S. anginosus. S. equisimilis was isolated from 3.0% of patients and 2.2% of controls, and S. anginosus was isolated from 11.1% of patients and 11.0% of controls. Thus, S. equisimilis and S. anginosus are both members of the normal flora of asymptomatic individuals. The incidence and biochemical characteristics of these two species are similar in patients who are healthy and those who have disease. However, a companion article provides clinical evidence associating S. equisimilis (but not s. anginosus) with pharyngitis. PMID- 8463391 TI - Role of group C beta-hemolytic streptococci in pharyngitis: epidemiologic study of clinical features associated with isolation of group C streptococci. AB - All Lancefield group C beta-hemolytic streptococci isolated over 12 months from college students with clinical pharyngitis and age-matched healthy controls were identified. Clinical features of upper respiratory tract infection and pyogenic pharyngitis as well as colony counts were tabulated for each patient according to throat culture results. Of 1,480 patients, Lancefield group C Streptococcus equisimilis was isolated from 45 (3%) patients and Streptococcus anginosus ("Streptococcus milleri") was isolated from 164 (11.1%) patients. Patients from whom S. equisimilis was isolated had clinical features more suggestive of pyogenic infection than did patients from whom S. anginosus was isolated. Colony counts on primary throat culture plates from patients from whom S. equisimilis and Streptococcus pyogenes were isolated were higher than those from patients from whom S. anginosus was isolated. This study presents epidemiologic evidence supporting a role for S. equisimilis in causing pharyngeal infection and for S. anginosus as representing part of the normal oropharyngeal flora. PMID- 8463392 TI - Evaluation of immunoglobulin E-specific antibodies and viral antigens in nasopharyngeal secretions of children with respiratory syncytial virus infections. AB - Enzyme immunoassays were developed to detect the presence of specific immunoglobulin E (IgE) antibodies and respiratory syncytial (RS) virus structural proteins in nasopharyngeal secretions in order to improve the knowledge on some aspects of the pathogenesis of severe acute lower respiratory tract infections caused by RS virus. These assays were used to analyze clinical specimens from children with RS virus-associated infections (bronchiolitis and pneumonia), and the findings were correlated with the patients' clinical symptoms. The results indicate the presence of specific IgE against the two external glycoproteins (G and F) and the absence of detectable IgE levels for the internal viral antigens. There was a correlation between the levels of IgE-specific antibodies and the amount of viral protein F in the secretions, indicating that the IgE response against the viral glycoproteins might be related to the antigen load. In addition, a correlation was found between higher levels of both viral protein F specific IgE and F antigen with higher respiratory rates in children with pneumonia. These findings may be relevant because they suggest an association between the virus load and the immune response in the pathogenesis of RS virus infections. PMID- 8463393 TI - Effect of heterosubtypic immunity on infection with attenuated influenza A virus vaccines in young children. AB - Resistance to infection with an influenza A virus conferred by previous infection with an influenza A virus belonging to another subtype is called heterosubtypic immunity. Heterosubtypic immunity is demonstrable in laboratory animals but is believed to be weak in humans. The present study examined whether heterosubtypic immunity from previous influenza virus infection induced resistance to infection with an attenuated influenza A vaccine virus. Two groups of vaccinees consisting of young infants and children who received either influenza A H1N1 or H3N2 attenuated virus were studied. Influenza A H3N2 virus vaccine recipients were classified by their preexisting H1N1 heterosubtypic antibody level induced by prior infection with wild-type virus, and the H1N1 vaccinees were classified by their history of infection with H3N2 vaccine virus. For both groups of vaccinees, the rates of seroconversion and virus shedding and the level of vaccine virus replication were compared in subjects with and without heterosubtypic immunity. In 48 influenza A H3N2 virus and 39 H1N1 virus vaccinees, heterosubtypic immunity had no demonstrable effect on infectivity, immunogenicity, or replication of attenuated vaccine virus. These observations confirm the weak nature of heterosubtypic immunity in humans and suggest that it will not limit the utility of live attenuated influenza A viruses in young infants and children. PMID- 8463394 TI - Novel, rapid optical immunoassay technique for detection of group A streptococci from pharyngeal specimens: comparison with standard culture methods. AB - A novel immunoassay system based on the changes in the reflection of light, termed an optical immunoassay (OIA), was utilized to directly detect group A streptococcal (GAS) carbohydrate antigen from clinical specimens. In two studies, a total of 1,275 throat swabs were tested for the presence of this antigen with the Strep A OIA rapid detection system and the results were compared with those of standard culture methods. In both studies, the Strep A OIA yielded more positive results than plating of the throat swab onto a selective agar, Trypticase soy agar containing sheep blood, or an enriched broth. In one study, the sensitivity and specificity of Strep A OIA compared with those of the broth enriched culture were 97.4 and 95.6%, respectively. In a second study a sensitivity of 98.9% and a specificity of 98.6% were achieved. It was also shown that the carbohydrate antigen could be detected in the absence of viable GAS organisms. The Strep A OIA is an easily interpretable method and was shown to be more sensitive than routine culture methods for detecting GAS infections directly from throat swabs. PMID- 8463395 TI - Evaluation of commercially available acridinium ester-labeled chemiluminescent DNA probes for culture identification of Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, and Histoplasma capsulatum. AB - Four commercially available acridinium ester-labeled DNA probes directed against rRNA were evaluated for their ability to identify Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and Cryptococcus neoformans in culture. rRNA was extracted by sonication of 1- to 2-mm2 portions of cultures of fungi in two chaotropic reagents with glass beads. Following a heat inactivation step, the extracts were hybridized in solution with probes specific for each pathogen. The acridinium ester reporter moiety of nonhybridized probe was selectively hydrolyzed, and chemiluminescence of specific DNA:RNA hybrids was quantitated in relative light units with a luminometer. A positive identification required a relative light unit value of > or = 50,000. Sensitivity and specificity of the probes were determined by probing cultures of the respective pathogenic fungi (target) and nontarget fungi. Both mycelial and yeast forms of the dimorphic fungi (B. dermatitidis and H. capsulatum) were tested. For B. dermatitidis, sensitivity and specificity were 87.8 and 100%, respectively (74 target and 219 nontarget fungi tested). For C. immitis, sensitivity and specificity were 99.2 and 100%, respectively (122 target and 164 nontarget fungi tested). For H. capsulatum, sensitivity and specificity were 100 and 100%, respectively (86 target and 154 nontarget fungi tested). For C. neoformans, sensitivity and specificity were 97 and 100%, respectively (100 target and 230 nontarget fungi tested). For B. dermatitidis, C. immitis, and C. neoformans, repeat testing increased the respective sensitivities to 97.3, 100, and 100%. The high sensitivities and specificities of the probes, the relatively short time (less than 1 h) required to perform the assay, and the availability of standardized reagent kits make the acridinium ester-labeled DNA probes well suited to laboratories in need of a rapid method to identify these fungal pathogens. Further, use of the probes to identify pathogenic fungi as soon as colonies appear on primary recovery media significantly shortens the time to reporting. PMID- 8463397 TI - Computerized surveillance in clinical microbiology with time series analysis. AB - An automatic surveillance system to detect changes in the incidences of microorganisms diagnosed in the department of clinical microbiology has been developed. The program is incorporated into the laboratory computer system and gives a weekly list of microorganisms whose isolation rates compared with those of a previous period exceed a chosen limit. The system uses time series analysis with moving weighted averages, and the detection limit is based on the distribution of the residuals. Output from the system included information about potential outbreaks of gastroenteritis, nosocomial infection with Corynebacterium jeikeium, and a seasonal epidemic of respiratory syncytial virus. The system also listed organisms not commonly isolated in the laboratory and detected incorrect reports. We conclude that continuous surveillance of laboratory data with time series analysis is a valuable tool for epidemiologic surveillance and quality control. Large quantities of data may be screened. PMID- 8463396 TI - Characterization of enterotoxigenic Escherichia coli isolated from U.S. troops deployed to the Middle East. AB - Enterotoxigenic Escherichia coli (ETEC) was a common cause of traveler's diarrhea in U.S. soldiers in the Middle East in 1989 and 1990. To determine which bacterial components would be useful in a vaccine, potential protective antigens (toxin, colonization factor antigen [CFA], and serotype) from 189 ETEC isolates were examined. Nearly half of the isolates expressed both ETEC toxins, 39% had only heat-stable enterotoxin (ST), and 17% had heat-labile enterotoxin (LT). CFA/I was the least common colonization factor antigen (11%), CFA/II was common (34%), as was CFA/IV (31%), and 24% expressed none of these CFAs. Fifty-seven O:H serotypes were found. Serotype O6:H16 was the most common, occurring in 29% of the ETEC isolates, usually with LT-ST and CFA/II. Generally, CFA/II was associated with expression of both toxins, CFA/IV was associated with expression of ST, and none of the CFAs was routinely found with LT. We conclude that ETEC from soldiers in the Middle East expressed a variety of antigens and that an effective vaccine will require multiple protective antigens. PMID- 8463398 TI - Improved recovery of mycobacteria from respiratory secretions of patients with cystic fibrosis. AB - Pulmonary colonization and infection of patients with cystic fibrosis by Mycobacterium spp. has recently been recognized as a potentially important clinical problem. However, frequent contamination of mycobacterial cultures by pseudomonads has hampered efforts to define the extent of this problem. This study was done to evaluate current techniques and to establish a more efficient method of recovering mycobacteria from respiratory secretions of patients with cystic fibrosis. Decontamination of respiratory specimens (n = 121) with 0.25% N acetyl-L-cysteine and 1% sodium hydroxide (NALC-NaOH) was associated with a high rate of pseudomonas overgrowth for both Lowenstein-Jensen slants (74%) and BacTec vials supplemented with PANTA (polymyxin B [50 U/ml], amphotericin B [5 micrograms/ml], nalidixic acid [20 micrograms/ml], trimethoprim [5 micrograms/ml], azlocillin [10 micrograms/ml]) (36%). This overgrowth limited recovery of mycobacteria to only 64% (9 of 14) of specimens positive by smear for acid-fast bacilli (AFB). Decontamination of specimens (n = 441) with NALC-NaOH, followed by 5% oxalic acid treatment, resulted in contamination of only 5% of Lowenstein-Jensen slants and 3% of BacTec vials. AFB were recovered from all 90 AFB smear-positive specimens following the use of this decontamination technique. We recommend that respiratory secretions be decontaminated with NALC-NaOH and oxalic acid to decrease the incidence of Pseudomonas aeruginosa overgrowth. PMID- 8463399 TI - Controlled comparison of the BACTEC high-blood-volume fungal medium, BACTEC Plus 26 aerobic blood culture bottle, and 10-milliliter isolator blood culture system for detection of fungemia and bacteremia. AB - The BACTEC high-blood-volume fungal medium (HBV-FM) (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) was compared with the Isolator (IS) tube and the BACTEC Plus 26 (BP26) blood culture bottle for the ability to recover fungi from the blood of adult patients suspected of having fungemia. A total of 6,836 blood culture sets that fulfilled criteria for inclusion in the study were received. Three separate comparisons were performed: 4,907 HBV-FM versus IS, 4,886 BP26 versus HBV-FM, and 4,949 BP26 versus IS. For the HBV-FM versus IS comparison, 218 isolates were recovered: 125 (57.3%) were bacteria and 93 (42.7%) were fungi. HBV FM was comparable to IS for recovery of yeasts, but IS was superior for recovery of Histoplasma capsulatum (25 versus 0 isolates recovered [P < 0.001]). Growth of Torulopsis glabrata was detected earlier (P < 0.05) in HBV-FM bottles. For the BP26 versus HBV-FM comparison, 229 isolates were recovered: 161 (70.3%) were bacteria, and 68 (29.7%) were fungi. HBV-FM was superior for recovery of T. glabrata (P < 0.025) and all fungi combined (P < 0.025). There were no statistically significant differences in the speed of detection of microbial growth. For the BP26 versus IS comparison, 251 isolates were recovered: 165 (65.7%) were bacteria, and 86 (34.2%) were fungi. IS was superior for recovery of H. capsulatum (P < 0.001), T. glabrata (P < 0.05), and fungi other than H. capsulatum (P < 0.025). BP26 was superior for recovery of all bacteria combined (P < 0.001) and viridans group streptococci (P < 0.01). Growth of T. glabrata (P < 0.05) was detected earlier in IS tubes. Growth of Staphylococcus aureus (P < 0.01), viridans group streptococci (P < 0.01), Pseudomonas aeruginosa (P < 0.05), and all microorganisms combined (P < 0.05) was detected earlier in BP26 bottles. For yeast, 57 of 59 (96.6%), 79 of 80 (98.7%), and 64 of 67(95.5%) were recovered from BP26 bottles, HBV-FM bottles, and IS tubes, respectively, by day 14; for H. capsulatum, 14 of 36 (38%) isolates were recovered from IS tubes by day 14. Mean times of recovery were similar for BACTEC bottles and IS. We conclude that (i) for recovery of fungi from blood cultures, HBV-FM is equivalent to IS (with the exception of H. capsulatum); (ii) for recovery of bacteria, BP26 is superior to IS; (iii) BP26 bottles are inferior to both HBV-FM bottles and IS tubes for recovery of T. glabrata; and (iv) HBV-FM bottles must be paired with another blood culture bottle or system to optimize detection of bacteremia. PMID- 8463400 TI - Determination of carbohydrate profiles of Bacillus anthracis and Bacillus cereus including identification of O-methyl methylpentoses by using gas chromatography mass spectrometry. AB - Bacillus anthracis and Bacillus cereus are closely related pathogenic organisms that are difficult to differentiate phenotypically or genotypically. It is well known that vegetative and spore forms of bacilli are quite distinct both morphologically and chemically, but spore-specific chemical markers allowing these species to be distinguished have not been previously described. By using gas chromatography-mass spectrometry, vegetative cells and spores of the two species were shown to exhibit distinct carbohydrate profiles. Profiles of vegetative B. anthracis typically contained high levels of galactose but did not contain galactosamine, whereas B. cereus contained galactosamine and generally low levels of galactose. Spore cultures exhibited unique carbohydrate profiles compared with those of vegetative cultures. B. anthracis spore profiles contained rhamnose alone, whereas B. cereus spore profiles contained rhamnose and fucose. Additionally, two spore-specific O-methylated methylpentoses were discovered. Both B. anthracis and B. cereus spores contained 3-O-methyl rhamnose, whereas B. cereus spores also contained 2-O-methyl rhamnose. Carbohydrate profiling is demonstrated to be a powerful tool for differentiating the two closely related species. Differentiation does not depend on whether organisms are in the vegetative or spore stage of growth. PMID- 8463401 TI - Evaluation of polymerase chain reaction amplification of Mycobacterium leprae specific repetitive sequence in biopsy specimens from leprosy patients. AB - Biopsy specimens were obtained from 102 leprosy patients before chemotherapy and examined by polymerase chain reaction (PCR) using the primers amplifying the 372 bp DNA of a repetitive sequence of Mycobacterium leprae. The PCR results were then compared with bacterial indices (BI) of slit-skin smears and biopsy specimens. The intensities of DNA bands were in general correlated with the numbers of acid-fast bacilli, and even a sample with only one organism gave a PCR positive result. Ten 5-micron sections from each frozen tissue sample were pooled and processed for DNA preparation. PCR was positive for 11 (73.3%) of 15 biopsy specimens with BI of 0 determined for the paraffin sections from the same biopsy samples. PCR also gave positive results for 84 (96.6%) of 87 BI positive biopsy samples. Although the difference in overall results between the two methods was not statistically significant, PCR seemed to have an advantage over microscopic examination in detecting M. leprae in biopsy specimens negative for acid-fast bacilli. Further evaluation of PCR using more specimens from leprosy patients who are bacteriologically negative is warranted to ensure PCR's advantage over the conventional microscopic examination for the diagnosis of leprosy. PMID- 8463402 TI - Evaluation of commercial antisera for serotyping heat-labile antigens of Campylobacter jejuni and Campylobacter coli. AB - Commercial antisera for serotyping 22 heat-labile antigens of Campylobacter jejuni and Campylobacter coli were evaluated by using 66 isolates from human and nonhuman sources. Test results were compared with results of tests using antisera produced at the Centers for Disease Control (CDC), Atlanta, Ga. All strains (three isolates of each of the 22 serotypes) were typeable with the CDC antisera. Of 66 test strains, 39 (59%) were typed as the same serotype with both sets of antisera. Twenty-four strains (36%), including two heat-labile serotype reference strains, were nonreactive with the commercial antisera, and three strains (4.5%) were typed as serotypes different from those obtained with CDC antisera. Five of the 22 commercial antisera correctly serotyped all homologous strains. Our study indicated that two polyvalent antiserum pools, 7 unabsorbed antisera, and 16 absorbed monovalent antisera are weak and need modification to enhance their antibody titers. Further studies are necessary to explain the antigenic change to a different serotype in three strains. PMID- 8463403 TI - Rapid, polymerase chain reaction-based identification assays for Candida species. AB - Polymerase chain reaction (PCR) amplification of specific regions in the genomes of a variety of lower eukaryotes permits rapid identification of these microorganisms. First, on the basis of the presence of both constant and variable regions in the small subunit (ssu) rRNA, a nested PCR for direct identification of various Candida species can be designed. Amplification of the entire ssu rRNA gene and subsequent reamplification of variable sequences within the V4 domains of these PCR products were combined with direct sequencing. Restriction enzyme maps were made, and species-specific oligonucleotides for hybridization analysis were selected. Unequivocal discrimination of four of the major human pathogenic yeasts (Candida albicans, Candida glabrata, Candida tropicalis, and Candida krusei) is possible if a combination of these techniques is used. Second, by using oligonucleotides aimed at repeated sequences which occur at dispersed positions in the genomes of all eukaryotes, species-specific DNA fingerprints could be generated. This interrepeat PCR using genomic DNA as template proved to be an effective tool in Candida species typing. Both techniques described here can be extrapolated to the high-speed diagnostics of numerous other prokaryotic and eukaryotic pathogens. PMID- 8463404 TI - Comparison of three enzyme immunoassays, a cytotoxicity assay, and toxigenic culture for diagnosis of Clostridium difficile-associated diarrhea. AB - Enzyme immunoassays (EIAs) based on monoclonal antibodies for the detection of Clostridium difficile toxins have recently been developed for clinical use. The aim of this study was to compare three commercially available EIAs, two for toxin A (Premier C. difficile Toxin A; Meridian, Osi, Elancourt, France; and Vidas C. difficile Toxin A; bioMerieux, Marcy l'Etoile, France) and one for toxins A and B (Cytoclone A + B EIA; Cambridge Biotech Corp., Codiapharm, Evian, France), with a cytotoxicity assay and toxigenic culture for the diagnosis of C. difficile associated diarrhea (CDAD). The study was performed with 285 fresh stools from 285 patients with suspected CDAD. In case of disagreement, the tests were repeated on a frozen aliquot of the same stool sample, and the patient's chart was reviewed. CDAD diagnosis was established in 55 cases (incidence, 19.3%). The sensitivities and specificities of the methods were, respectively, 92.7 and 100% for the cytotoxicity assay, 96.4 and 99.1% for toxigenic culture, 75.5 and 97.8% for Cytoclone, 65.4 and 99.6% for Premier, and 65.4 and 100% for Vidas. The results were uninterpretable in 3.2% of cases with Cytoclone, 0.3% with Premier, and 2.5% with Vidas. We conclude that the cytotoxicity assay and toxigenic culture remain the best methods for the diagnosis of CDAD even though they lack standardization and require 48 to 96 h to obtain the result. Despite their rapidity and simplicity, EIAs are not sensitive enough to be relied on as the sole laboratory test. PMID- 8463405 TI - Rapid screening test for enterotoxin-producing Bacillus cereus. AB - Culture supernatants of 30 enterotoxin-producing Bacillus cereus isolates produced a characteristic progressive destruction of McCoy cell monolayers. Enterotoxin-negative B. cereus and other group 1 Bacillus spp. caused no monolayer disruption. The McCoy cell tissue culture system appears to provide a rapid screening assay for detection of enterotoxin-producing B. cereus. PMID- 8463406 TI - Random amplified polymorphic DNA assay is less discriminant than pulsed-field gel electrophoresis for typing strains of methicillin-resistant Staphylococcus aureus. AB - Twenty-six strains of methicillin-resistant Staphylococcus aureus with different pulsed-field gel electrophoresis fingerprints were tested by random amplified polymorphic DNA assay with three primers, resulting in 15 to 20 different random amplified polymorphic DNA fingerprints. By summing the results for the three primers, the number of different fingerprints increased to 25, but two strains could not be differentiated. We conclude that pulsed-field gel electrophoresis remains the best method of typing methicillin-resistant S. aureus strains. PMID- 8463407 TI - Mycobacteriosis due to Mycobacterium genavense in six pet birds. AB - Six cases of mycobacteriosis due to Mycobacterium genavense in three budgerigars (Melopsittacus undulatus), one orange-winged amazon (Amazona amazonica), one flycatcher (Cyanoptila cyanomelana), and one zebra finch (Taeniopygia guttata) are discussed. Gross lesions associated with the infection included a high degree of muscular wasting (five cases), hepatomegaly (four cases), and thickening of the wall of the small intestine (four cases). Granulomas were found in the lung (one case) and the subcutis (one case). Acid-fast bacilli were detected in the liver of all six birds. Only the use of acidic BACTEC mediums consistently led to growth, whereas the egg-based medium failed. These findings point to a possible role of the environment as a reservoir for M. genavense. PMID- 8463408 TI - Increased specificity of antibody detection in surgical patients with invasive candidiasis with cytoplasmic antigens depleted of mannan residues. AB - In this study, it was shown that the diagnostic accuracy of antibody detection by a counterimmunoelectrophoresis technique could be improved by using cytoplasmic antigens depleted of mannan residues. The specificity of the counterimmunoelectrophoresis increased from 28.6 to 78.6% when cytoplasmic antigens depleted of mannan were used, while the sensitivity slightly decreased from 80 to 70%. PMID- 8463409 TI - Detection of serum antibodies to Chlamydia trachomatis in patients with chlamydial and nonchlamydial pelvic inflammatory disease by the IPAzyme Chlamydia and enzyme immunoassay. AB - A novel serological test, IPAzyme Chlamydia (Savyon Diagnostics Ltd., Beer Sheva, Israel), was compared with an enzyme immunoassay (EIA) for the ability to detect serum immunoglobulin G and A antibodies in the diagnosis of acute chlamydial pelvic inflammatory disease. In comparison with cell culture, which is the "gold standard," IPAzyme Chlamydia and EIA exhibited sensitivities of 63 and 68% and specificities of 76 and 87%, respectively. Thus, IPAzyme Chlamydia offers no advantages over the EIA, and neither serological test can be recommended for the diagnosis of acute Chlamydia trachomatis infection. So far, conventional cell culture remains the most reliable diagnostic test for chlamydial pelvic inflammatory disease. PMID- 8463410 TI - How to tackle a possible Creutzfeldt-Jakob disease necropsy. PMID- 8463411 TI - ICSH recommendations for measurement of erythrocyte sedimentation rate. International Council for Standardization in Haematology (Expert Panel on Blood Rheology) AB - The Expert Panel on Blood Rheology of the International Council for Standardization in Haematology (ICSH) has prepared new recommendations for measurement of the erythrocyte sedimentation rate (ESR) under the following categories: 1. ICSH reference method-ICSH now recognises, as its reference method for the ESR, the sedimentation of EDTA-anticoagulated but undiluted blood in traditional Westergren pipettes that meet ICSH specifications. 2. ICSH standardised method-ICSH recommends specifications for a new standardised method for the ESR based on the sedimentation of EDTA-anticoagulated, but undiluted blood in pipettes with a 200 mm scale and which are designed to avoid spillage of blood or aerosol generation. This standardised method may be used for verification or quality control of other ESR methods and, in future, may replace the reference method. 3. ICSH selected methods-ICSH recommends specifications for working methods, using diluted or undiluted blood, which may be considered as ICSH selected methods for routine use. A protocol is outlined for evaluation of such working methods against the ICSH reference method or the new ICSH standardised method. PMID- 8463413 TI - Observer reliability in assessing villitis of unknown aetiology. AB - AIMS: To evaluate observer variation in diagnosis of villitis of unknown aetiology. METHODS: Fifty haematoxylin and eosin stained sections were circulated to three pathologists who were asked to assess if villitis was present. These slides, with an additional 20, were recirculated and reassessed by the same pathologists. RESULTS: Intra-observer agreement was 84.7% (range 74--92%) and interobserver agreement was 81%. A conjoint review by the three pathologists revealed that sources of differences included the overlooking of isolated single or small numbers of affected villi, the difficulty in assessing stromal cellularity close to infarcted parenchyma, and apparent stromal hypercellularity in immature villi. CONCLUSIONS: Experienced pathologists can show a significant interobserver variation in assessing villitis of unknown aetiology. Future studies on villitis of unknown aetiology should address the problem of observer reproducibility of diagnosis. PMID- 8463412 TI - Expression of c-myc and c-fms oncogenes in trophoblastic cells in hydatidiform mole and normal human placenta. AB - AIMS: To compare the expression of c-myc and c-fms proto-oncogenes in the placenta and hydatidiform mole. METHODS: Twelve hydatidiform moles and six induced abortion cases were collected. c-myc and c-fms proto-oncogene expression was analysed by northern blot hybridisation and immunohistochemical staining. RESULTS: The results of northern blot hybridisation analysis showed that c-fms was expressed more strongly in hydatidiform moles compared with normal placenta of similar gestational age. Moreover, c-fms mRNA concentrations increased with more advanced gestational age in moles but not in normal placentas. c-myc expression was very low in hydatidiform moles and normal placentas. Both oncogenes, however, had no direct correlation with the clinical course of the molar pregnancies. CONCLUSION: The difference in c-fms expression between hydatidiform moles and normal placentas suggests that c-fms may have a role in the development of molar pregnancies. PMID- 8463414 TI - Pulmonary platelet aggregates: possible cause of sudden peroperative death in adults undergoing liver transplantation. AB - AIMS: To determine if massive pulmonary platelet thromboembolism is a common cause of peroperative death following liver transplantation; and to compare the incidence of this event with patients dying after non-transplantation procedures. METHODS: Necropsy tissues from all patients dying within 10 days of operation during the past three and a half years were studied (six liver transplantations and 13 unrelated operations). Haematoxylin and eosin stained sections of all tissues were examined. Additional sections of lung tissue were immunostained for constituents of thrombus (fibrin and platelets). RESULTS: At necropsy the lungs from all six liver transplant recipients were heavy with a rubbery texture and little oedema fluid. Those from non-transplantation patients appeared normal or very oedematous. Microscopic examination showed that there were numerous platelet aggregates occluding pulmonary capillaries in all six transplant recipients, but in only three of the non-transplant patients. These thrombi were numerous in patients dying during surgery and the number was underestimated in routine sections because of the surrounding capillary congestion. Detection was improved by immunostaining for platelets with factor XIIIA and platelet glyco-protein IIIa. CONCLUSIONS: Massive platelet thromboembolism is a likely cause of death in patients dying unexpectedly following recent liver transplantation. Non transplantation patients dying during surgery who show similar appearances usually have conditions known to have a high risk of thrombosis or embolism (cement hypotension syndrome and disseminated intravascular coagulation). The cause of this extensive platelet activation in liver transplant recipients is uncertain and may be multifactorial. The unusual rubbery consistency of the lungs on macroscopic examination could alert the pathologist to the underlying condition. Immunostaining for platelets improves the detection microscopically. PMID- 8463415 TI - Radiation disease of the urinary tract: histological features of 18 cases. AB - AIMS: To study the spectrum of histological changes in the urinary tract caused by pelvic irradiation. METHODS: Biopsy specimens of ureter and bladder and cystectomy specimens from 18 patients who had received pelvic irradiation were studied and the histological features were arbitrarily grouped into early and late changes. RESULTS: A wide range of histological changes were noted of which submucosal inflammation, fibrosis, and epithelial damage were the commonest. Other less common features were interstitial haemorrhage, ureteritis and cystitis cystica, squamous metaplasia of vaginal type and perineural inflammation. CONCLUSIONS: Although epithelial changes were most prominent in early cases and stromal changes in the late cases, there was a continuing spectrum of epithelial damage which persisted many years after initial radiation. Similarly, submucosal fibrosis was equally prominent in early and late phases. PMID- 8463416 TI - Certifying the cause of death: an audit of wording inaccuracies. AB - AIMS: To audit wording and formulation inaccuracies in certifying the cause of death. METHODS: Five hundred causes of death were analysed from the counterfoils of medical death certificates (Form 66). Wording and formulation inaccuracies were defined as terms contrary to the notes given to doctors in books on death certificates. RESULTS: One or more inaccuracies were identified in 29% of cases. In 5.8% of cases, the inaccuracies were sufficiently serious to warrant further action or enquiry by the Registrar of Births and Deaths, including referral to Her Majesty's Coroner. CONCLUSIONS: Most inaccuracies could have been avoided by adhering to the notes for medical practitioners contained in books of death certificates. The wording and formulation of causes of death warrants special prominence in under-graduate and postgraduate medical education. The topic should be audited and medical practitioners should pay particular attention to cases worthy of referral to HM Coroner. PMID- 8463417 TI - Bile reflux and intestinal metaplasia in gastric mucosa. AB - AIM: To determine associations between enterogastric bile reflux and gastric mucosal pathology. METHOD: A retrospective study using fasting gastric juice bile acid measurements and antral or prestomal biopsy specimens from 350 patients, 66 of whom had previously undergone surgery that either bypassed or disrupted the pyloric sphincter. RESULTS: Bile reflux was positively associated with reactive gastritis and negatively with Helicobacter pylori density. After stratification for previous surgery, age, and H pylori status, the histological feature most strongly associated with bile reflux was intestinal metaplasia, including all its subtypes. The prevalence of intestinal metaplasia was greatest in patients with both H pylori infection and high bile acid concentrations. Bile reflux was also positively associated with the severity of glandular atrophy, chronic inflammation, lamina propria oedema and foveolar hyperplasia. CONCLUSIONS: Bile reflux is a cause of reactive gastritis. It modifies the features of H pylori associated chronic gastritis. The changes are not confined to patients who have had surgery to their stomachs. The positive associations with atrophy and intestinal metaplasia have implications for models of gastric carcinogenesis. PMID- 8463418 TI - Mucin exocytosis: a major target for Helicobacter pylori. AB - AIMS: To determine whether Helicobacter pylori impairs the secretory function of mucous cells. METHODS: The mucus secreting human cell line CL. 16E, maintained as confluent monolayers on nitrocellulose filters, was infected with H pylori strain CIP 101260. After three hours of incubation with H pylori the monolayers were washed and reincubated with fresh culture medium for various time periods (24, 48, or 72 hours) before evaluating both the morphology and function of mucous cells. For morphological studies, epithelial monolayers were fixed in situ and processed for both standard histochemistry on paraffin wax sections, and electron microscopy. To measure mucins secreted from cultured cells, the cells were metabolically labelled with 3H-glucosamine. Undegraded mucins were quantitated as the radioactive glycoproteins blocked at the stacker gel interface after sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the secretory glycoproteins. RESULTS: Control cultures of CL. 16E cells grew on filters as homogeneous monolayers of polarised mucous cells secreting a visco-elastic gel of mucins at the apical surface. In infected monolayers H pylori was in close contact with the apical surface of mucous cells. Cell counts and histological evaluation of the monolayers did not reveal any significant deleterious effect of H pylori on the mucous cells. H pylori induced only a modest inhibition of baseline mucus secretion from CL. 16E cells, this inhibition being significant only at 24 hours. In contrast, the mucus secretory response to two agents that raise intracellular cAMP and calcium--forskolin and ionophore A23187--was strongly inhibited. The inhibitory effect of H pylori on the exocytotic response was not paralleled by an inhibition of glycoprotein synthesis. CONCLUSION: Considering the fact that the exocytotic response to a variety of secretagogues constitutes the primary line of defence of the gastric mucosa in an emergency, it is suggested that H pylori exerts its deleterious effects by weakening this important physiological defence. PMID- 8463419 TI - Assay of gastricsin and individual pepsins in human gastric juice. AB - AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease. PMID- 8463420 TI - Comparison between liver and serum concentrations of mannan binding protein. AB - AIMS: To investigate staining patterns for mannan binding protein (MBP) by immunocytochemistry in liver biopsy specimens from patients with various hepatic disorders; to measure the serum MBP concentration in the patients at the time of biopsy; and to compare these to define further the role of MBP in disease. METHODS: Fifty seven consecutive patients with a variety of types of liver disease were studied. Fresh liver biopsy specimens were immunostained with anti MBP and graded for intensity of staining. Serum MBP concentrations were measured on samples obtained on the day of biopsy, as were a full range of liver blood tests. RESULTS: MBP was only detectable in liver biopsy specimens from patients with morphological evidence of liver disease. MBP was most prominent in the livers of patients with severe alcoholic liver disease; livers harbouring metastases or showing biliary disease had moderate concentrations. Patients with liver disease were more likely to have raised serum MBP concentrations, but there was no correlation between these values and those found in the biopsy specimens. There was also no significant correlation between either of these concentrations and liver blood test abnormalities. CONCLUSIONS: Patients with liver disease tend to have raised MBP concentrations in both the liver and serum, but the exact relation between the two is as yet undefined. PMID- 8463421 TI - Is serum creatine kinase:aspartate aminotransferase ratio useful for diagnosing acute myocardial infarction in elderly patients? AB - AIM: To evaluate the usefulness of the serum creatine kinase: aspartate aminotransferase (CK:AST) ratio in differentiating between myocardial and non myocardial increases in serum creatine kinase activity in the elderly. METHODS: A three month prospective study of all patients admitted to an acute geriatric unit who were clinically assessed and investigated with electrocardiograms and measurement of CK, AST, and lactate dehydrogenase (LDH) activities on the first three days of admission. Excluding those with liver disease and alcohol misuse, patients with increased CK activity were then classified into four groups depending on whether they had fallen or had an acute myocardial infarction (AMI), or both. RESULTS: 270 patients were evaluated. CK activity was raised in 86 (31%) patients on any of the first three days of admission. Of these, 31 had fallen, 19 had an AMI, and five had both fallen and sustained an AMI. The CK:AST ratio, on all days, was higher (p < 0.05) in those who had fallen. On the second and third days, the CK:AST ratio was higher (p < 0.01) in those patients who did not have an AMI. The overlap, however, between these groups was large. CONCLUSIONS: These results did not allow discrimination to be made between myocardial and skeletal sources for increased CK activity. The CK:AST ratio is, therefore, of limited use when applied to the diagnosis of AMI in elderly patients. Clinical evaluation rather than the pattern of enzyme change is more likely to determine the cause of increased CK activity. PMID- 8463422 TI - Lipoprotein (a) as an independent risk factor for myocardial infarction in patients with common hypercholesterolaemia. AB - AIMS: To examine whether lipoprotein (a) (Lp(a)) increases the risk of myocardial infarction (MI) in patients with common hypercholesterolaemia. METHODS: 15 middle aged men with common hypercholesterolaemia (mean serum low density lipoprotein (LDL) cholesterol 4.94 mmol/l, SD 1.0) and a history of MI were selected consecutively from referrals to a lipid clinic. A control group that had not sustained an MI and with similar age, sex, cigarette smoking and blood pressure characteristics was also selected from the same clinic. Serum cholesterol, triglyceride, LDL cholesterol, high density lipoprotein cholesterol, apolipoproteins AI and B and Lp(a) were measured in both groups. Lp(a) was assayed by immunoturbidity. RESULTS: The serum concentration of Lp(a) was significantly higher in patients with MI (geometric mean 0.64 (95% confidence interval 0.36 to 1.14) v 0.30 (0.21 to 0.42) g/l, p = 0.02), but there were no significant differences in other variables. Stepwise logistic regression analysis showed that Lp(a) was the only significant predictor of MI (p < 0.02). The odds ratio of MI (adjusted for age, smoking, blood pressure and apolipoprotein B) for an Lp(a) of > 0.57 g/l was 16.5, 95% confidence interval 2.3 to 125.4 (p = 0.001). CONCLUSION: In middle aged men with common hypercholesterolaemia the serum concentration of Lp(a) is a powerful and independent risk factor for MI. Lp(a) should probably be routinely measured in all patients referred to a lipid clinic. PMID- 8463423 TI - Fatal pulmonary infection due to Mycobacterium fortuitum. AB - Environmental (atypical, opportunist, other) mycobacteria were first isolated nearly a century ago. The classification of these "other than Mycobacterium tuberculosis" organisms was initially chaotic until Runyon proposed a scheme of four groups in 1959. Mycobacterium fortuitum is a member of group IV: Rapid growers. These ubiquitous terrestrial and aquatic forms contaminate water supplies, reagents, and clinical samples. They may colonise the respiratory systems of patients whose local defence mechanisms have been impaired or those with congenital and acquired immune defects. They can also cause disease in immunocompetent individuals. There have been fewer than 20 published cases of pulmonary infection caused by M fortuitum. A further case is reported of fatal pulmonary infection in an elderly patient with long standing chronic obstructive airways disease (COAD). He had left upper zone shadowing on chest radiography and lung abscesses at post mortem examination yielded only M fortuitum. PMID- 8463424 TI - Human T lymphotropic virus type I associated myelopathy with pulmonary and cutaneous lesions. AB - A necropsy case of human T lymphotropic virus I (HTLV-I) associated myelopathy (HAM) in a 64 year old man with serological and genetical confirmation of HTLV-I infection is reported. The spinal cord, lung, and skin were mainly affected. Severe degeneration had occurred in the spinal cord, not only in the lateral columns but also in the anterior and posterior columns. The degenerate lesions showed proliferation of capillaries, loss of myelin and axon, and perivascular and parenchymal infiltration with T lymphocytes and foamy macrophages in the white matter. T lymphocytes had infiltrated the lung and there was vascular proliferation in the peribronchus. OPD4 positive cells predominated in the lung. The patient also had erythrodermia where dense and bandlike HTLV-I infected lymphoid cell infiltration was observed, with mild atypia and epidermotropism. HTLV-I may cause multiorganic inflammatory disorders, although the definitive role of HTLV-I in the pathogenesis is still unknown. PMID- 8463425 TI - Needle tract implantation of thymoma after transthoracic needle biopsy. AB - A 73 year old woman was admitted to hospital because of an anterior mediastinal mass. For definite diagnosis, needle biopsy was performed under fluoroscopic observation. The histopathological diagnosis was thymoma and combination chemotherapy was given. The tumour almost completely disappeared and the patient was discharged. But the tumour recurred in the left anterior chest wall four months later. It is suggested that the thymoma tissue had been implanted in the needle tract. PMID- 8463426 TI - Biochemical diagnosis of phaeochromocytoma: two instructive case reports. AB - The biochemical features of two patients with phaeochromocytomas illustrate the inadvisability of depending on a single group of analytes for the diagnosis. The first case presented as a surgical emergency with retroperitoneal haemorrhage. Biochemical diagnosis was difficult since total 24 hour urinary free catecholamine excretion was within normal limits in two out of three samples, and only marginally raised in the third with an atypical preponderance of adrenaline. Plasma catecholamine concentrations were also normal. But urinary excretion of the catecholamine metabolites, metadrenaline and 4-hydroxy-3-methoxy mandelic acid (HMMA), was consistently raised. In contrast, the second patient presenting with headache and labile hypertension showed normal metabolite excretion in the face of grossly increased free noradrenaline excretion and raised plasma noradrenaline concentrations. It is therefore recommend that, as well as urinary free catecholamines, one group of their main metabolites, the 3-methoxy amines (normetadrenaline and metadrenaline) or HMMA, should routinely be measured whenever a phaeochromocytoma is suspected. PMID- 8463427 TI - Determination of serum cholesterol concentration in the presence of ascorbate. AB - Pretreatment of a serum or plasma sample with ascorbate oxidase removed interfering ascorbate and allowed the determination of cholesterol to be carried out by a current enzymatic cholesterol method available in kit form. The Cobas Fara was programmed to carry out pretreatment of the sample with ascorbate oxidase before addition of the cholesterol colour reagent. PMID- 8463428 TI - Misunderstandings about methyl methacrylate. PMID- 8463429 TI - Sentinel and Bactec blood culture systems. PMID- 8463430 TI - Staging and follow up of patients with lymphoproliferative disorder. PMID- 8463431 TI - Farmer Jesty and the discovery of vaccination. PMID- 8463432 TI - Intramammary lymph nodes. PMID- 8463433 TI - Pediatric pharmacology: the path clears for a noble mission. AB - Unlabeled use of drugs in children occurs frequently and contributes to the therapeutic orphan dilemma. This situation can no longer be condoned; few acceptable reasons still exist for not evaluating potentially effective drug therapy in children. An apparent lack of research funds is not one of these reasons; only allocation of these funds to pediatric pharmacology is found wanting. Availability of clinical pharmacology programs, pediatric pharmacology manpower, sensitive analytical techniques, and acceptable ethical approaches to pediatric research reveal that drug evaluation is feasible in children. Studies readily include the required therapeutic indication for drug use in pediatrics. Efforts of academia, government and industry are now converging to show that the path for the noble mission of pediatric pharmacology--rational use of FDA approved drugs for children--is now clear for action. PMID- 8463434 TI - Adverse effects of drugs and chemicals in breast milk on the nursing infant. AB - Breastfeeding is an essential physiologic process that provides nutrition to the infant and protects the child against infection and immunologic disorders. The incidence of various diseases and metabolic disorders is known to be less in a breastfed infant compared with a child given a milk substitute. Psychologically, a breastfed infant forms a maternal bond that enables adaptation more readily to a social environment. It is well-established that all drugs are excreted into breast milk and are bioavailable to the infant. In general the majority of drugs do not pose a significant problem to the nursing infant and breastfeeding should be encouraged. The physician should be aware of which drugs are contraindicated during lactation and which drugs should be used with caution. There are also environmental chemicals that readily enter breast milk and may induce adverse effects. At present, the advantages of breastfeeding for infant development outweigh the potential adverse consequences and this physiologic process should be encouraged. With the use of available data on pharmacokinetics, milk-to-plasma ratio, excretion, etc. a supportive approach can be delineated by the pediatrician to reassure the nursing mother that they can safely breastfeed and continue therapy with minimal effects on the infant. It is thus imperative to document the extent to which a drug or chemical appears in breast milk and any apparent effects in the infant. PMID- 8463435 TI - The influence of pretreatment periods with diltiazem on nifedipine kinetics. AB - The effect of durations of diltiazem pretreatment on nifedipine kinetics was evaluated. Eighteen healthy male subjects were randomly allocated to three groups, 6 subjects each, for single doses of 60 mg diltiazem, and 3 days and 6 days with diltiazem 60 mg three times a day. All subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo controlled method. No significant difference on pharmacokinetic parameters of nifedipine without diltiazem were observed among three groups. The single dose with 60 mg diltiazem significantly increased the area under the plasma concentration-time curve (AUC) for nifedipine compared with that in control an average of 35.1% (P < .05) and decreased the total body clearance (CL) an average of 24.0% (P < .05). Three days and 6 days pretreatment with diltiazem 60 mg three times a day significantly increased mean nifedipine AUC to 151.1% (P < .01), 188.0% (P < .05) of control values, and decreased CL to 58.2% (P < .01), 63.9% (P < .05) of control values, respectively. The elimination half-life (t1/2) of nifedipine were significantly prolonged both after 3 days' and after 6 days' pretreatment of diltiazem. These results suggest that diltiazem affects the nifedipine kinetics rapidly and pretreatment duration dependently. A clinically important drug interaction may occur when both drugs are administered simultaneously. PMID- 8463436 TI - Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. AB - Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage. PMID- 8463437 TI - The effect of stress on glycemic control in patients with type II diabetes during glyburide and glipizide therapy. AB - Stress adversely affects glycemic control in patients with type II diabetes mellitus. In addition, stress reduction with relaxation techniques or medication use in the management of hyperglycemia has been recommended. This study examined the relationship of glycemic control to self-reported stress in 19 patients with type II diabetes mellitus who were randomly allocated to receive either glyburide or glipizide for 16 weeks in a double-blind crossover design. Each treatment phase was preceded by a 2-week washout period. A previously designed and validated nine-item stress questionnaire was used to assess areas such as safety, financial wellbeing, energy level, health, etc. These areas were evaluated as more/less, better/worse, or no change. The stress questionnaire, fasting blood glucose (FBG), and glycosylated hemoglobin (GHb) concentrations were completed or measured at the end of glyburide and glipizide treatment periods. By assigning a value of 1, 2, or 3 to a positive, no change, or negative response, respectively, a composite stress score was computed and compared with glycemic control as assessed by FBG and GHb. Regression analysis showed highly significant correlations (P < .05) between stress scores and FBG (r = .70) as well as GHb (r = 0.84) with glipizide therapy. No such correlation was noted with glyburide (FBG: r = 0.29; GHb: r = 0.29). These findings suggest that during glyburide treatment, in contrast to glipizide, an increase in stress was not associated with a corresponding rise in blood glucose or worsening of metabolic control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463438 TI - Performance of human mass balance/metabolite identification studies using stable isotope (13C, 15N) labeling and continuous-flow isotope-ratio mass spectrometry as an alternative to radioactive labeling methods. AB - Stable isotope labeling in therapeutic and subtherapeutic quantities of drug (15N2(13)C-phenobarbital) can be quantitated in biological matrices (urine) and high performance liquid chromatography (HPLC) peaks from urine using continuous flow isotope-ratio mass spectrometry (CF-IRMS). Standard curves for 15N2(13)C phenobarbital were reproducible and linear (R2 > 0.985) over the ranges of 3-100 micrograms/ml for whole urine (15N2 or 13C labeling) and 0.1-8.0 micrograms/mL for HPLC peaks derived from urine (15N2 labeling). The lower limit of quantitation values for urine drug concentration was 0.46-2.62 micrograms/mL in whole urine and 0.10-0.70 micrograms/mL in HPLC peaks. Validation samples quantitated with these standard curves yielded close to expected values. These data suggest stable isotope labeling and CF-IRMS may be used as an alternative to 14C labeling and radioactivity counting methods in mass balance/metabolite identification and other biomedical studies. PMID- 8463439 TI - Clinical use of androgenic steroids at a major medical center: who prescribes androgens and how well do they do it? AB - To assess prescribing practices for androgens at Wilford Hall USAF Medical Center, the authors analyzed prescriptions for all patients receiving therapy during a 12-month period (n = 201) and reviewed the available outpatient records not maintained elsewhere (n = 105). The most commonly prescribed androgens were testosterone enanthate (144/201; 56.7%), and danazol (52/201; 25.9%). Review of the available outpatient medical records of 73 male patients using testosterone enanthate showed a mean age of 59.5 years, mean frequency of injection of 20 days, mean duration of therapy of 3.5 years, and mean dose of 226 mg. Therapy was initiated by a urologist (34/73; 46.6%), an endocrinologist (33/73; 45.2%), or an internist (6.73; 8.2%). Indications for therapy based on pretreatment laboratory and historical data included hypergonadotropic hypogonadism (24/73; 32.9%), hypogonadotropic hypogonadism (23/73; 31.5%), unspecified hypogonadism (7/73; 9.6%), and empiric treatment of elderly men with erectile dysfunction without evidence of hypogonadism (9/73; 26%). Pretreatment prostate examinations as well as measurement of serum testosterone (66/73; 90.4%) and serum gonadotropins (52/73; 71.2%) were often not performed. The authors conclude that records of patients treated with androgens show: 1) Doses are appropriate; 2) Empiric treatment of erectile dysfunction in elderly men is common despite the associated risks; 3) Laboratory and physical evaluation before treatment is often incomplete; 4) There was no evidence of androgenic substance abuse in patients studied. PMID- 8463440 TI - Risk factors not addressed in antihypertensive therapy based solely on blood pressure control. AB - There has been a considerable revolution in the field of hypertension therapy. We have gone through an era in which patients with severe hypertension and those with accelerated hypertension had a very short life expectancy. Currently blood pressure can be readily controlled with a marked improvement in longevity. We have gone from an era in which stroke was common due to hypertensive cardiovascular disease to an era in which patients are effectively treated and there has been a marked reduction in the incidence of stroke. The challenge is whether we can reduce the very high mortality due to coronary artery disease in patients with hypertension as we have done with stroke. New groups of drugs that may have a more favorable effect on metabolic and hemodynamic risk considerations have been developed over the last decade. These agents may reduce the risk for coronary heart disease to a greater extent than previously employed therapy. While there are no randomized placebo-controlled studies demonstration this, a theoretical basis does exist to give the physician reason to think about prioritizing therapies and tailoring them to the needs of the individual patient. PMID- 8463441 TI - Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects. AB - Zolpidem is a rapid-onset, short-duration imidazopyridine hypnotic drug and is specific agonist of the omega-1 (BZD1) receptors. Its hypnotic characteristics resemble those of triazolam. The aims of this study were to assess the effects of zolpidem on memory (the main objective), psychomotor performances, and postural sway (secondary objectives) in 18 healthy subjects and to compare them with those of triazolam and placebo. Short- and long-term memory (paired words associate and pictures test), psychomotor performances (critical flicker fusion frequency, choice reaction time, digit symbol substitution test), and postural sway were evaluated before and 1.5, 4, 6, and 8 h after the administration of a single dose of zolpidem (10 mg), triazolam (0.25 mg), and placebo. For each assessment, the maximal effect for both hypnotic drugs occurred 1.5 hour after intake. Both drugs decreased psychomotor performance, impaired memory, and increased postural sway. The effects of both hypnotic agents were short lasting, and no alterations were found 6 and 8 hours, respectively, after drug intake. No clinically relevant differences were found between zolpidem and triazolam for memory, psychomotor performance, postural sway, or adverse effects. It may be concluded that zolpidem, like triazolam, impairs short- and long-term memory, psychomotor performances, and postural sway and that these effects are of short duration. PMID- 8463442 TI - Open prospective trial of fluoxetine for posttraumatic stress disorder. AB - Twenty-seven patients with combat-related posttraumatic stress disorder (PTSD) entered an open, prospective, 10-week trial of fluoxetine, beginning with 20 mg/day and increasing to 80 mg/day until response was optimal or side effects prohibited dose increase. Nineteen patients completed 3 or more weeks and were included in the data analysis. Total Clinician-Administered PTSD Scale scores decreased from a mean of 64.5 at baseline to 42.7 at endpoint (F = 7.17, p < 0.001), and improvement was significant in each of the three PTSD subscales (reexperiencing, avoidance/numbing, and hyperarousal). Depression and anxiety ratings showed similar improvements, and suicidality ratings did not increase. Global improvement scores decreased from 4.0 at baseline to 2.67 at endpoint (F = 12.08, p < 0.001); however, improvement in social and occupational functioning was minimal. Appreciable improvement tended to occur after 6 weeks, suggesting that higher fluoxetine doses and/or duration than that used for depression may be indicated in this population. Panic attack frequency decreased by at least 50% in six of eight patients who kept panic diaries. The high dropout rate reflects problems with side effects, anxiety symptoms, external events, and substance abuse. Our data suggest that fluoxetine is effective in reducing reexperiencing, avoidance, and hyperarousal symptoms of PTSD, and this improvement is independent of comorbid panic disorder. In addition, fluoxetine appears to be effective in reducing panic attacks in PTSD patients. The efficacy of fluoxetine for some PTSD patients is interesting in light of emerging neuropharmacologic data suggesting serotonergic dysregulation in some PTSD patients. Noradrenergic hypotheses are also discussed. The findings should be confirmed by double-blind, placebo controlled studies. PMID- 8463443 TI - Imipramine is effective after unsuccessful cognitive therapy: sequential use of cognitive therapy and imipramine in depressed outpatients. AB - As a partial test of whether the same or different patients benefit from cognitive therapy and tricyclic antidepressant agents, depressed outpatients first received cognitive therapy, then nonresponders were treated with either imipramine or placebo. If the two treatments were effective for the same subgroup of patients, imipramine should not be more effective than placebo because potential responders should already have been removed by treatment with cognitive therapy. Alternatively, if cognitive therapy and imipramine are effective for different subtypes of depressive disorder, then imipramine ought to be more effective than placebo for patients failing to benefit from cognitive therapy because some potential imipramine failures would already have been removed. Thirty-six depressed outpatients were treated with weekly cognitive therapy for 16 weeks with 17 (47%) responding. Nonresponders were then randomly assigned to imipramine or placebo for 6 weeks to a maximum dose of 300 mg of imipramine per day. Of 12 patients completing the double-blind medication trial, all 5 assigned to imipramine had a clear-cut response, whereas none of the other seven benefited from placebo (chi 2 = 12.00; p = 0.001). Although the numbers are small, these results suggest rejection of the hypothesis that imipramine is effective for the same subpopulation of depressed patients as is cognitive therapy. PMID- 8463444 TI - The assessment and clinical implications of haloperidol acute-dose, steady-state, and withdrawal pharmacokinetics. AB - In order to evaluate comprehensively haloperidol pharmacokinetics under fixed dose treatment conditions, psychiatric patients were studied after treatment with an acute dose, during maintenance therapy, and after withdrawal from haloperidol following steady-state conditions. After single doses, haloperidol appeared rapidly in serum, achieving peak concentration at a mean of 4.5 hours. The range of observed elimination half-life was broad, between 8.5 and 66.6 hours, with a mean of 19.5 hours. Under conditions of chronic dosing, serial measurements of steady-state serum concentration revealed intrapatient coefficients of variation between 2 and 72%. The mean for all patients was 26.4%. Body clearance decreased nonsignificantly, and elimination half-life increased significantly after chronic dosing compared with kinetic parameters determined after a single dose. The concentration of haloperidol in serum obtained at 8 hours after a single dose correlated most strongly (r = 0.73; p < 0.0001) with steady-state concentration resulting from chronic dosing. A value of 4 ng/ml or lower determined 8 hours after a single oral dose of 0.2 mg/kg identified patients who did not accumulate haloperidol during chronic dosing of 0.4 mg/kg per day above a presumed therapeutic range for haloperidol of 5 to 15 ng/ml. The implications of these data for the clinical use of haloperidol are discussed. PMID- 8463445 TI - Prolongation of the corrected QT and torsades de pointes cardiac arrhythmia associated with intravenous haloperidol in the medically ill. AB - Consultation psychiatrists are frequently called upon by their medical and surgical colleagues to assist in the management of agitated, delirious patients in the intensive care unit. Intravenous haloperidol has a reputation for safe and effective sedation of these patients and has been found to be free of many of the dangerous anticholinergic and cardiac side effects of the lower-potency neuroleptics. The authors report the cases of three patients who developed torsades de pointes arrhythmia or lengthening of the Q-T interval during treatment with intravenous haloperidol. The cases suggest that the use of intravenous haloperidol should be accompanied by cardiac monitoring and that risk factors for torsades de pointes during haloperidol treatment may include dilated cardiomyopathy and a history of alcohol abuse. PMID- 8463446 TI - A systematic approach to the classification and pharmacotherapy of nonpsychotic major depression and dysthymia. AB - Nonpsychotic depressive and dysthymic states are reclassified and reorganized in order to maximize relevance to clinical psychopharmacology. In the initial phase of assessment, patients are divided into two easily recognized categories: mood nonreactive (autonomous) depression and mood-reactive depression. After family and past history of response and cost of drug are considered, a tricyclic antidepressant is usually selected for autonomous depression patients, and mood reactive depression patients are initially given a serotonin reuptake inhibitor. Nonresponders from either category are changed to the alternative medication or have it added to their first drug. Nonresponders to both of these initial trials are then assessed for the presence of atypical depression symptoms by the Columbia criteria. If these symptoms are present, the patients may be offered a third medication trial with a monoamine oxidase inhibitor. Bupropion could be the choice if the monoamine oxidase inhibitor cannot be given expeditiously. This completes the initial assessment and treatment phase. Autonomous and mood reactive patients who do not respond to this sequence of interventions are then reassessed for the presence of characterologic syndromes and comorbidity with some frequently encountered conditions. These may determine the choice of medication and the prognosis for a positive result from the next choices selected. When possible, specific recommendations are given for the various situations. PMID- 8463447 TI - Prolonged psychotic relapse after abrupt clozapine withdrawal. PMID- 8463448 TI - Transient fever and hematologic abnormalities during clozapine use. PMID- 8463449 TI - A naturalistic follow-up of panic patients after short-term pharmacologic treatment. PMID- 8463450 TI - Clomipramine treatment of sexual preoccupation. PMID- 8463451 TI - Pharmacotherapy in the prevention of suicidal behavior. PMID- 8463452 TI - Combining drugs and electroconvulsive therapy: safe and/or effective? PMID- 8463454 TI - Systemic sclerosis. AB - Systemic sclerosis affects the connective tissue of various organs. It is characterized by alteration of the microvasculature with a dense inflammatory cellular infiltrate, followed by massive deposition of collagen. This review discusses diagnostic criteria, clinical subsets, survival data, clinical evaluation, epidemiology, pathogenesis, immunobiology, genetics, and therapy for systemic sclerosis in adults. Because the diagnosis of systemic sclerosis is most dependent on its cutaneous involvement, knowledge of this is essential in the evaluation and management of patients with this disorder. PMID- 8463453 TI - Acute interactions of buprenorphine with intravenous cocaine and morphine: an investigational new drug phase I safety evaluation. AB - Recent preclinical and clinical studies suggest that buprenorphine, an opioid mixed agonist-antagonist, may be useful for the treatment of dual dependence on cocaine and opiates. This report describes an inpatient clinical evaluation of the safety of buprenorphine alone and in combination with single doses of cocaine and morphine. Twenty subjects with a DSM-III-R diagnosis of concurrent cocaine and opioid dependence were randomly assigned to maintenance treatment with single daily doses of 4 or 8 mg of sublingual buprenorphine for 21 days. Side effects and vital signs were evaluated every day once every 8 hours and for 2 hours after daily buprenorphine administration. The physiologic effects of a single-blind challenge dose of cocaine (30 mg intravenously), morphine (10 mg intravenously), and intravenous saline placebo were measured before and during buprenorphine maintenance. Before buprenorphine maintenance, subjects underwent methadone detoxification followed by a 9-day drug-free period. Three baseline single-blind challenge dose studies were conducted on study days 7, 8, and 9 during the drug free period. Cardiovascular responses to cocaine and to morphine were equivalent under drug-free and buprenorphine maintenance conditions. Respiration and temperature changes in response to cocaine were also equivalent before and during buprenorphine maintenance. Respiratory rates were slightly lower after morphine administration during maintenance on 8 mg of buprenorphine, but this was not statistically significant. Mild opioid agonist-like side effects were reported during buprenorphine induction and maintenance. These included headache, sedation, nasal discharge, abdominal discomfort, and anxiety. Most opioid agonist side effects decreased within 12 to 14 days. An electrocardiogram and blood chemistry measures were normal before and during buprenorphine maintenance. These data suggest that daily maintenance on buprenorphine is not associated with adverse side effects or toxic interactions with a single acute dose of intravenous cocaine or morphine. PMID- 8463455 TI - Characterization of T-cell clones generated from skin of patients with psoriasis. AB - BACKGROUND: The infiltrating cells in psoriasis include a subpopulation of autoreactive T cells. OBJECTIVE: The aim of this study was to further characterize skin-infiltrating T lymphocytes in patients with psoriasis. METHODS: Forty-five T-cell clones were generated from skin biopsy specimens from two patients. RESULTS: Phenotypic studies on 25 of 45 clones revealed that 19 (76%) of the clones were CD4+, 5 (20%) were CD8+, and 1 (4%) clone was CD4- and CD8-. Twenty-three clones were stained for identification of T-cell receptors. Twenty two clones expressed alpha/beta T-cell receptors and one clone (CD4-/CD8-) expressed no T-cell receptor. Nineteen clones (42%) were autoreactive with no restriction to class I or class II HLA antigens. By contrast, proliferation of two of the seven clones was inhibited by class I monoclonal antibody, whereas proliferation of four of seven clones was inhibited by class II monoclonal antibody. CONCLUSION: These data suggest that skin-infiltrating lymphocytes in patients with psoriasis may recognize HLA-associated molecules, perhaps the peptide of the HLA groove. The recognition of the peptide is presumably inhibited when monoclonal antibody is bound to the HLA molecule. PMID- 8463456 TI - Familial and cutaneous features of dysplastic nevi: a case-control study. AB - BACKGROUND: Although dysplastic nevi are an important risk factor for melanoma, little is understood about the epidemiology of these nevi. To further characterize some of the correlates of dysplastic nevi, we reexamined patients from one of the original prevalence reports and their first-degree relatives. OBJECTIVE: Our purpose was to characterize the prevalence and correlates of dysplastic nevi. METHODS: We studied 25 persons originally diagnosed with dysplastic nevi in 1980 and 1981, 28 controls stratified by age, sex, race, and date of initial examination, and all willing first-degree relatives of both patients (n = 78) and control subjects (n = 76). Each study subject underwent a full skin examination and biopsy of nevi suspected of being dysplastic nevi, if willing. RESULTS: Eighty percent of the case kindreds were multiplex (2 members or more affected) for dysplastic nevi; the relative risk of having dysplastic nevi was 7.2 (95% confidence interval 2.1 to 24) if one or more relatives had dysplastic nevi. Three of the cases (12%) in multiplex families also had a first degree relative with melanoma. Cases and relatives with dysplastic nevi of both patients and control subjects tended to have increased numbers of nevi. The risk of having dysplastic nevi rose 99-fold in persons with more than five nevi 4 mm or larger and/or scars on their back (p < 0.001). CONCLUSION: These data support the hypothesis that family members of unselected persons with dysplastic nevi are likely to have dysplastic nevi and may be at increased risk of melanoma. PMID- 8463457 TI - Pigmented spindle cell nevus: a clinicopathologic analysis of ninety-five cases. AB - BACKGROUND: Pigmented spindle cell nevus (PSCN) is often interpreted as a Spitz nevus or misdiagnosed as malignant melanoma. OBJECTIVE: The purpose of this study was to analyze the clinical and histologic features and to determine the biologic behavior of 95 cases of PSCN. METHODS: We reviewed clinical data, follow-up information, and microscopic features of all 95 cases of PSCN. RESULTS: PSCNs are dark brown to black, 3 to 6 mm in diameter, and occur most commonly on the extremities (75%) and back (16%) with a predilection for the legs. These lesions are more common in women in the third decade of life. Microscopically, PSCNs are characterized by uniform, spindle-shaped, pigmented melanocytes. Although some histologic features overlap with those in spindle and epithelioid cell nevus, PSCN is a separate entity. In addition, PSCN must be differentiated from malignant melanoma. Fifty-seven patients (60%) observed for an average of 6 years did not develop local recurrence or metastasis. CONCLUSION: PSCN is a distinctive, acquired, benign melanocytic lesion, that should not be confused with spindle and epithelioid cell nevus or malignant melanoma. Complete excision is recommended for treatment. PMID- 8463458 TI - Parenteral administration of 8-methoxypsoralen in photopheresis. AB - BACKGROUND: Extracorporeal photochemotherapy (EP) is used for the treatment of cutaneous T-cell lymphoma (CTCL), progressive systemic sclerosis (PSS), pemphigus vulgaris, and rheumatoid arthritis. During this procedure, the oral administration of the photoactive drug 8-methoxypsoralen (8-MOP) results in an unpredictable range of serum levels and in side effects limiting its efficacy. OBJECTIVE: To circumvent this limitation, extracorporeally administrable 8-MOP (EX-8-MOP) was developed. It is administered directly to the leukocyte/plasma concentrate in the treatment bag of the EP apparatus before irradiation with UVA light. METHODS: Efficacy, tolerance, and side effects of EX-8-MOP were evaluated in 108 consecutive treatments of 16 patients who had previously been treated with oral 8-MOP (91 treatments). RESULTS: With EX-8-MOP constant drug levels for UV light exposure were obtained; for equivalent levels only a small fraction of the oral dose (1/250 to 1/500) was required with none of the side effects associated with oral 8-MOP. Effective and reproducible inhibition of lymphocyte proliferation and cell viability was attained. No difference in clinical efficacy could be observed. CONCLUSION: EX-8-MOP eliminates the need for premedication and drug level monitoring of 8-MOP and should improve the effectiveness of EP. PMID- 8463459 TI - Abnormal lymph drainage in patients with chronic venous leg ulcers. AB - BACKGROUND: Edema often occurs in association with venous leg ulcers. OBJECTIVE: Our purpose was to assess lymphatic function in the legs of patients with venous leg ulcers. METHODS: Quantitative lymphoscintigraphy was performed in 22 normal control subjects, 32 patients with venous leg ulcers, and 7 patients with varicose veins only. RESULTS: Lymph drainage declined with age in the normal controls (r = -0.57; p = 0.0001). Lymphatic function was reduced in the ulcerated legs compared with normal limbs (age < 65 years; p < 0.0001) and in edematous legs compared with nonedematous legs (age > 65 years; ulcerated legs, p = 0.016; nonulcerated legs, p = 0.021). Lymph drainage was lower in the legs of patients with varicose veins only (p = 0.004). CONCLUSION: Impaired lymphatic function is associated with both venous leg ulcers and chronic venous hypertension. PMID- 8463460 TI - Malignant melanoma in xeroderma pigmentosum: search for a precursor lesion. AB - BACKGROUND: Malignant melanomas occur with increased frequency and at an early age in patients with xeroderma pigmentosum (XP). OBJECTIVE: The purpose of this study was to describe the histologic features of malignant melanomas in patients with XP and to search for a possible precursor lesion. METHODS: Clinical records and hematoxylin-eosin-stained sections of 19 malignant melanomas from seven patients with XP were examined. A search was conducted for malignant melanoma precursor lesions (melanocytic nevi and solar lentigines lateral to and contiguous with the malignant melanomas). Basal cell carcinomas removed from the same patients were used as controls. RESULTS: Malignant melanomas were characteristically found in biopsy specimens of small elevations and/or changed color foci arising in large, flat, darkly pigmented, gradually enlarging macules. Histologically, solar lentigo was lateral to and contiguous with malignant melanoma in 88% of the malignant melanomas. Transitional areas were present. A significantly lower number (22%) of contiguous solar lentigines, without transitional areas, were observed in the basal cell carcinoma controls. Most of the invasive malignant melanomas were spindle cell malignant melanomas. CONCLUSION: We propose that solar lentigo is the most common precursor lesion of malignant melanoma in patients with XP. PMID- 8463461 TI - Long-term oral antibiotics for acne: is laboratory monitoring necessary? AB - BACKGROUND: The role of laboratory monitoring in patients receiving long-term oral antibiotics for acne vulgaris has not been clearly defined. OBJECTIVE: The purpose of our study was (1) to evaluate the literature for objective evidence on the value of routine laboratory monitoring of the asymptomatic patient receiving oral antibiotics for acne and (2) to determine the utilization of laboratory monitoring of these patients by Connecticut dermatologists. METHODS: We surveyed Connecticut dermatologists by phone and inquired about the laboratory monitoring performed in patients receiving long-term oral tetracycline, minocycline, or erythromycin for acne. RESULTS: Eight published studies reported a total of 777 patients who had laboratory monitoring at various frequencies while receiving oral antibiotics for acne. Only one adverse drug reaction (ADR) was detected in a patient in whom mild hyperbilirubinemia developed. Of the 75 Connecticut dermatologists who participated in our survey, 48 (64%) perform some laboratory monitoring; 29% do so routinely, and 35% under special circumstances. CONCLUSION: Our literature review does not support routine laboratory monitoring in all patients who receive long-term oral antibiotics for acne; rarely does such screening detect an ADR and thus does not justify the cost of such testing. A relatively small proportion of Connecticut dermatologists check laboratory tests more frequently than appears necessary; in our opinion, laboratory monitoring should be limited to patients who may be at higher risk for an ADR. PMID- 8463462 TI - Pruritus in the elderly: management by senior dermatologists. AB - BACKGROUND: Pruritus in older patients is common, yet remains a challenge for clinicians. By virtue of their years of experience and older age, senior dermatologists may have developed opinions and approaches that are insightful. METHODS: A random sample of board-certified dermatologists older than 64 years of age was surveyed by a written anonymous questionnaire to assess their opinions, diagnostic approaches, and treatments of pruritus and xerosis in the older adult. RESULTS: The 63 respondents whose surveys were analyzed believe the most common cause of generalized pruritus in the elderly is xerosis. Of those respondents who believe laboratory evaluation is necessary for generalized pruritus in this population, a complete blood cell count and a multichemistry panel were the most frequently ordered tests. Treatment regimens and products recommended were highly variable and included topical emollients, corticosteroids, and others. The most common systemic agent employed was hydroxyzine hydrochloride, followed by corticosteroids, doxepin, diphenhydramine, and terfenadine. Various topical, physical, and miscellaneous treatments were recommended. CONCLUSION: This study provides a glimpse into the diagnostic and therapeutic approaches of senior dermatologists. PMID- 8463463 TI - Hydroxychloroquine sulfate (Plaquenil) improves oral lichen planus: An open trial. AB - BACKGROUND: Oral lichen planus is chronic and can be debilitating. Topical corticosteroids are most frequently used for treatment, but they are not always effective. OBJECTIVE: Hydroxychloroquine sulfate (Plaquenil), an antimalarial agent, was evaluated in an open trial (10 patients) for its ability to improve oral lichen planus. METHODS: Patients received hydroxychloroquine, 200 to 400 mg daily, as a monotherapy for 6 months. Patients were assessed at baseline and every 4 to 8 weeks during treatment. Baseline ophthalmologic examinations were performed, and laboratory values were monitored before and during treatment. RESULTS: Nine of ten patients had an excellent response to therapy. Three of six patients with erosions at baseline had complete healing. Pain relief and reduced erythema were usually observed after 1 to 2 months of therapy, but erosions required 3 to 6 months of treatment before they resolved. There were no adverse effects. CONCLUSION: Hydroxychloroquine may be useful in the treatment of oral lichen planus. PMID- 8463464 TI - Contact allergy to corticosteroids. AB - Recent evidence shows that contact allergy to topical corticosteroids is more frequent than earlier believed. This review summarizes the current knowledge of this condition, including methods for clinical diagnosis. PMID- 8463465 TI - The clinical spectrum of lipodermatosclerosis. AB - Lipodermatosclerosis refers to the skin induration and hyperpigmentation of the legs that often occurs in patients who have venous insufficiency. Lipodermatosclerosis has also been termed hypodermitis sclerodermiformis and appears to be similar if not-identical to the recently described sclerosing panniculitis of the leg. There has been much confusion about the nature, clinical course, and treatment of lipodermatosclerosis. We believe that lipodermatosclerosis has an acute, inflammatory phase and a chronic, fibrotic stage, although a spectrum exists. Direct immunofluorescence studies of early and late lesions are helpful in that they show dermal pericapillary fibrin deposits without other immunoreactants. Treatment of lipodermatosclerosis consists of compression therapy with either graded stockings or elastic bandages. We and others have found that the anabolic steroid stanozolol improves this condition rapidly and consistently. PMID- 8463466 TI - Guidelines of care for cutaneous squamous cell carcinoma. Committee on Guidelines of Care. Task Force on Cutaneous Squamous Cell Carcinoma. PMID- 8463467 TI - Guidelines of care for psoriasis. Committee on Guidelines of Care. Task Force on Psoriasis. PMID- 8463468 TI - Guidelines of care for malignant melanoma. Committee on Guidelines of Care. Task Force on Malignant Melanoma. PMID- 8463469 TI - Melanoma screening: critique and proposal. PMID- 8463470 TI - Early detection of melanoma: an ounce of prevention may be a ton of work. PMID- 8463471 TI - Topical terbinafine and clotrimazole in interdigital tinea pedis: a multicenter comparison of cure and relapse rates with 1- and 4-week treatment regimens. PMID- 8463472 TI - Disseminated superficial porokeratosis: complete remission subsequent to discontinuation of immunosuppression. PMID- 8463473 TI - Congenital giant common blue nevus. PMID- 8463474 TI - Concurrent pemphigus and myasthenia gravis as manifestations of penicillamine toxicity. PMID- 8463475 TI - Phototesting and phototoxic side effects in bath PUVA. PMID- 8463476 TI - Lip leishmaniasis. PMID- 8463477 TI - Exogenous ochronosis. PMID- 8463478 TI - Lichen sclerosus as a cutaneous manifestation of thyroid disease. PMID- 8463479 TI - Tanning operators in North Carolina. PMID- 8463480 TI - Defining purpura. PMID- 8463481 TI - Cutaneous melanoma. PMID- 8463482 TI - Treatment of solar urticaria with terfenadine. PMID- 8463483 TI - Release of volatile branched-chain and other fatty acids from ruminant milk fats by various lipases. AB - Bovine, ovine, and caprine milk fats were treated with pregastric lipases (kid goat, calf, and lamb), microbial lipases (Candida cylindracea, C. cylindracea AY30, Aspergillus niger APF12, Rhizopus arrhizus, Penicillium roqueforti R10, and Mucor zavanicus Map 10), porcine pancreatic lipase, or milk lipase. All three pregastric lipases preferentially hydrolyzed volatile branched-chain and short n chain fatty acids from each milk fat. Pregastric lipases also released a relatively low proportion of C10 from bovine milk fats but a high proportion of C10 from caprine milk fat. Milk lipase released very low concentrations of butanoic acid and did not release 4-methyloctanoic acid in significant amounts except from caprine milk fat. Ovine milk fat yielded a substantially greater concentration of butanoic acid than did bovine or caprine milk fats when it was hydrolyzed by porcine pancreatic lipase. Candida cylindracea lipase yielded high amounts of volatile n-chain fatty acids nonselectively and only small quantities of volatile branched-chain fatty acids. High amounts of the medium-chain branched fatty acids were produced by kid goat, P. roqueforti, A. niger, and R. arrhizus lipases. PMID- 8463484 TI - Detection of estrus by radiotelemetric monitoring of vaginal and ear skin temperature and pedometer measurements of activity. AB - Methods to improve detection of estrus in dairy cows have been studied extensively without wide acceptance of any one method. In the present study, the use of body temperatures and pedometer-monitored activity were evaluated as methods of estrus detection. Twice daily activity levels of 13 lactating cows were monitored using pedometers, and vaginal and ear skin temperature measurements were made continuously using radiotelemetry. Activity increased 2.8 fold at estrus for the 8-h daytime period (0630 to 1430 h), during which cows were given a 5-h turnout period, but not for the 16-h overnight period (1430 to 0630 h), during which cows were confined to tie stalls. When increased activity was used to detect estrus on an individual cow basis, 20 of 25 estruses were detected with 4 false positives. Vaginal temperature increased by .6 +/- .3 degree C at estrus and remained elevated by at least .3 degree C for 6.8 +/- 4.6 h. When increased vaginal temperature was used on an individual basis, 17 of 21 estruses were detected with 3 false positives. Rate of detection of estrus by visual observation was 66%. PMID- 8463485 TI - Effects of intramammary endotoxin infusion on milking-induced oxytocin release. AB - One overt sign of clinical coliform mastitis in dairy cows is the failure to eject milk normally or to "milk out" the udder. The effect, if any, of coliform mastitis on oxytocin release is unknown. Therefore, the objective of this study was to determine the effect of endotoxin mastitis on milking-induced release of oxytocin in lactating cows. Fifteen multiparous pregnant lactating Holstein cows were divided into three groups of 5 cows each. Cows in group 1 served as controls and received an intramammary infusion of sterile physiological saline. Cows in groups 2 and 3 received intramammary infusions of 12.5 and 25 micrograms of Escherichia coli endotoxin, respectively. Serum concentrations of oxytocin were measured by radioimmunoassay before, during, and after milkings commencing at 6 and 12 h after treatment. Rectal temperatures and milk SCC were monitored to follow the course of inflammation and to verify the biological activity of infused endotoxin. Endotoxin resulted in a 1.5- to 2-fold increase in milking induced oxytocin release compared with that of control treatments. The effect was most prominent during the first 6 h after infusion and coincided with the peak pyretic response. This study shows that endotoxin-induced mastitis potentiates, rather than inhibits, milking-induced oxytocin release. PMID- 8463486 TI - The effect of manipulation in energy allowance during the rearing period of heifers on hormone concentrations and milk production in first lactation cows. AB - Fifteen Holstein heifers that were 175 +/- 4.0 d old and at BW of 175 +/- 4.9 kg were used to determine the effect of three feeding regimens from 6 to 12 mo of age on growth, blood concentration of several hormones, and milk production during first lactation. The feeding regimens consisted of two periods, the first lasting for 4 mo and the other for the subsequent 2 mo. For group A (restricted) heifers, the diet during period 1 was restricted to 85% of NRC (1988) recommendations (a daily BW gain of .7 kg); during period 2, a high energy, high protein diet was provided for ad libitum intake. Group B (control) heifers received a diet that corresponded to 100 and 90% of the NRC (1988) recommendations in periods 1 and 2, respectively. Group C (ad libitum) intake heifers received a high energy, high protein diet throughout both periods. Daily BW gains of heifers of groups A, B, and C were, respectively, .625, .768, and 1.100 kg for period 1 and 1.162, .705, and .797 kg for period 2. The different feeding regimens influenced the age at which the heifers achieved puberty but did not affect BW at puberty. Milk production during 250 d of lactation was 7056, 6070, and 5975 kg for groups A, B, and C, respectively. A statistical model that included serum derived mitogenic activity and serum prolactin of period 2 accounted for 63% of the difference in milk production at first lactation. PMID- 8463487 TI - Effects of decreased availability of glucose for dairy cows. AB - After a preliminary trial to establish dose responses to phlorizin, five Holstein cows at 6 wk postpartum were used to test the response of cows in negative energy balance to a sudden decrease in availability of glucose caused by phlorizin. Cows were fed equal amounts of feed twice daily to supply 100% of NRC recommendations for protein and 90% of NRC recommendations for NEL and were in negative energy balance throughout the experiment. Phlorizin at 0, 2, and 4 g/d was injected subcutaneously in equal amounts every 6 h for 48 h and caused excretion of 0, 225, and 337 g/d of glucose in urine. Milk production was not decreased, but percentage of milk fat increased linearly (3.34, 3.56, and 3.70%) with increasing phlorizin. Concentrations of glucose (64.2, 62.6, and 59.4 mg/dl) and insulin (518, 432, and 329 pg/ml) in blood plasma decreased linearly, whereas beta hydroxybutyrate (6.11, 8.88, and 9.98 mg/dl) and NEFA (181, 220, and 271 mu eq/L) increased linearly. The changes were most dramatic during the final 12 h of the 48-h injection interval. Healthy, early lactation cows in negative energy balance seem to have the capacity to make metabolic adjustments to provide adequate substrates for maintenance and milk synthesis and to compensate for short-term increased needs for glucose. PMID- 8463488 TI - Mammary amino acid utilization in dairy cows fed fat and its relationship to milk protein depression. AB - Changes in mammary AA utilization associated with dietary fat-induced milk protein depression were assessed in cows with disturbed AA status. Four first lactation cows fitted with rumen cannulas were assigned to a factorial arrangement of treatments: two diets and two casein infusion sites within a 4 x 4 Latin square design. Diets were formulated with yellow grease at 0 or 4% of DM. An 8% sodium caseinate solution was infused continuously at 5.04 kg/d into the rumen or abomasum during the last 5 d of each 21-d period. Arterial AA concentrations were reduced by dietary fat treatment and increased by abomasal sodium caseinate infusion. Mammary arteriovenous differences of essential AA tended to increase with both abomasal casein infusion and dietary fat treatments. With ruminal casein infusion treatments, yellow grease supplementation increased the percentage of extraction of blood essential AA into mammary tissue. Mammary blood flow rate dropped 7% on high fat treatments, preventing an increase in uptakes of critical AA to accompany the improved efficiency of milk synthesis, which was evident from a significantly reduced ratio of mammary blood flow to milk volume, resulting in depressed milk protein content. PMID- 8463489 TI - Diets containing high oil corn and tallow for dairy cows during early lactation. AB - Four multiparous Holstein cows averaging 49 DIM and fitted with ruminal cannulas were utilized in a 4 x 4 Latin square design with 21-d periods to determine the effects of diets containing high oil corn grain and tallow. Cows were fed diets of alfalfa haylage and concentrate (37:63, DM basis) for ad libitum intake. Treatments were 1) control, no added fat; 2) high oil corn grain replacing regular corn grain; 3) high oil corn grain and 2.5% tallow; and 4) high oil corn grain and 5% tallow. Intake of DM, milk production, and yields of milk fat, milk protein, milk SNF, and 4% FCM were not affected by dietary fat, although DMI tended to be lower when cows were fed 5% tallow. Percentages of protein and SNF in milk were lower when cows were fed diets containing fat. Percentage of milk fat was lower when cows were fed diets containing tallow. Supplemental fat decreased total VFA concentrations in ruminal fluid. Cows fed high oil corn had a greater molar proportion of acetate and a larger acetate to propionate ratio in ruminal fluid than cows fed high oil corn and tallow. Digestibility of total fatty acids decreased when tallow was added to diets containing high oil corn. No differences were observed among treatments for total tract apparent digestibilities of DM and fiber or utilization of energy and N. Dietary high oil corn and 5% tallow tended to decrease DMI and to alter ruminal fermentation characteristics. PMID- 8463490 TI - Selection of killer yeasts (Kluyveromyces lactis) to prevent aerobic deterioration in silage making. AB - Killer spectra were investigated to select killer yeast strains to inhibit the growth of wild yeasts that cause aerobic deterioration of silage. Kluyveromyces lactis IFO 1267 was characterized by its rapid killing activity and wide spectrum against the target yeasts. Crude killer protein produced by K. lactis IFO 1267 or inoculation of the cell itself inhibited the growth of the target strain, Saccharomyces cerevisiae IFO 0304 (in liquid or in solid culture), particularly when lactose was used as carbon source instead of glucose. PMID- 8463491 TI - Effect of protein quality and evaporative cooling on lactational performance of Holstein cows in hot weather. AB - Twenty-four Holstein cows in midlactation during summer in southern Arizona were fed diets supplemented with a combination of blood, fish, and soybean meals (high quality protein) or corn gluten meal (low quality protein). Diets were balanced for CP content and estimated ruminal protein degradability, but they differed in Lys concentration (.98 vs. .59% of DM). Milk yield for the 56-d trial was higher by 11% for cows fed high than for cows fed low quality protein and higher by 9% for cows receiving evaporative cooling plus shade than for cows receiving shade alone. Milk fat and protein yields also were greater for high than for low quality protein and for evaporatively cooled plus shade than for shade treatments. Intake of DM tended to be higher for cooled cows but was unaffected by protein source. Cooled cows had lower rectal temperatures (38.6 vs. 39.1 degrees C) and respiration rates (64 vs. 82/min) than noncooled cows. Interactions between protein quality and cooling method were not statistically significant; however, cooled cows fed high quality protein had higher milk yield than noncooled cows. Digestibility of DM was higher for the low than for the high quality diet, but CP digestibilities were not different. Cows fed supplemental protein of higher Lys content were more productive. PMID- 8463492 TI - Another theory for the action of ruminal buffer salts: decreased starch fermentation and propionate production. AB - Sodium carbonates have been fed to ruminants for more than 20 yr and, in many cases, have alleviated milk fat depression. These effects usually have been ascribed to increased ruminal buffering capacity, but this mode of action has several problems. For the buffering capacity to increase, the concentrations of ruminal bicarbonate, dissolved CO2, and Na have to increase. Ruminal fluid already is saturated with CO2, and the cation concentration of ruminal fluid is regulated closely to prevent hemoconcentration or hemodilution. Based on these latter observations, a significant increase in ruminal buffering capacity is unlikely. The action of bicarbonates is explained more easily by increased water intake, increased ruminal fluid dilution rate, increased flow of undegraded starch from the rumen, and decreased ruminal propionate production. PMID- 8463493 TI - Efficacy of a dried colostrum powder in the prevention of disease in neonatal Holstein calves. AB - The efficacy of a dried colostrum powder, DCW Concentrate, as a colostrum supplement or substitute was tested using four groups of 15 calves. Physical condition and IgG status were examined during the first 30 d of life. Calves were fed the dried colostrum powder (group A), pooled colostrum (group C), or both (groups B and D) 2 h after birth. Calves fed 85 g of the dried colostrum powder dissolved in 3 kg of whole milk (group A) had significantly lower IgG concentrations 24 h after birth than calves of the other groups. Administration of 85 g of the dried colostrum powder plus 3 kg of colostrum (group C) did not lead to significantly higher IgG concentrations 24 h after birth than did administration of 3 kg of colostrum alone (group B). Calves fed 85 g of the dried colostrum powder plus 1.5 kg of colostrum (group D) had an IgG concentration at 24 h of age that was not significantly different from that of calves given 3 kg of colostrum (group B). Morbidity and mortality rates were not significantly different among groups. One calf died in each of groups A and B; no losses occurred in groups C and D. Body weight increase was not significantly different among groups. PMID- 8463494 TI - Low incidence of citrullinemia carriers among dairy cattle of the United States. AB - Bovine citrullinemia is an autosomal recessive disorder that is lethal in the early postnatal period. Dairy bulls from the US were screened for citrullinemia genotype with a mutation-specific assay of semen or leukocyte DNA. One heterozygote was detected among 367 US Holstein bulls tested, corresponding to an incidence of .3%; DNA sequencing showed that this bull (bull C) was heterozygous for the translation-termination mutation described as the cause of bovine citrullinemia. Tests on daughters of bull C revealed that 26 were heterozygous and 25 were homozygous normal, confirming that the condition is autosomal recessive and that bull C was heterozygous. Although bull C was among 273 bulls tested from the top 400 bulls based on Type-Production Index as of July 1990, he was not among the 90 tested from the top 100. He has fewer than 2000 offspring registered with the Holstein Association of America and has few sons in AI. Furthermore, he was culled for other reasons before his citrullinemia status was known. Accordingly, the incidence of citrullinemia carriers is low among US Holsteins, and the impact of the one carrier found on the future of the breed is expected to be minor. No carriers were found among 102 US Guernsey bulls and 53 US Jersey bulls tested. PMID- 8463495 TI - Biological action of mycotoxins. AB - Mycotoxins are ubiquitous, mold-produced toxins that contaminate a wide variety of foods and feeds. Ingestion of mycotoxins cause a range of toxic responses, from acute toxicity to long-term or chronic health disorders. Some mycotoxins have caused outbreaks of human toxicoses, and at least one mycotoxin, aflatoxin B1, is a presumed human hepatocarcinogen. As part of a comprehensive effort to curtail the adverse health effects posed by mycotoxins, substantial research has been conducted to determine the mechanism of action of mycotoxins in animals. This review presents some of the current knowledge on the biological action of four diverse classes of mycotoxins--aflatoxin B1, tricothecenes, zearalenone, and fumonisin B1--with particular emphasis on mechanisms of action. PMID- 8463496 TI - Immunotoxicity of mycotoxins. AB - The immune system is primarily responsible for defense against invading organisms. The effects of several mycotoxins on the immune responses have been investigated; however, most data concern laboratory animals. In some instances, farm animals and cells derived from livestock species have been employed to evaluate the immunotoxicity of mycotoxins. Immune responses are highly variable, and cost considerations usually preclude the use of dairy cattle as experimental models. Immunosuppression caused by aflatoxin B1 has been demonstrated in various livestock species (e.g., turkeys, chickens, and pigs) and also in laboratory animals (mice, guinea pigs, and rabbits). The response of bovine lymphocytes to aflatoxin in vitro is similar to that of other laboratory animals. Trichothecenes are potent immunosuppressive agents that directly affect immune cells and also modify immune responses as a consequence of tissue damage elsewhere. Sheep and calves treated with fusarium T-2 toxin develop leukopenia and decreased functioning of peripheral lymphocytes. Immunosuppressive effects of ochratoxin A, rubratoxin B, and patulin have been reported. Citrinin produced lymphopenia but stimulated responses against antigens. Antibodies against mycotoxins conjugated to proteins have been produced and are useful for analytical purposes. PMID- 8463497 TI - Strategies of mold control in dairy feeds. AB - Mold growth can occur in dairy feeds only when nutrients are available, correct temperatures exist, oxygen is present, and unbound water is available. Because elimination of any one of these four factors prevents mold growth, management of feed that accounts for these elements is essential. Use of multiple ingredient mold inhibitors recently has become another tool for affecting successful microbiological control of feed. PMID- 8463498 TI - Acoustical Society of America, 125th meeting. Ottawa, Canada, 17-21 May 1993. Abstracts. PMID- 8463499 TI - The differential validity of hyperactivity/attention deficits and conduct problems among mentally retarded children. AB - The independence of hyperactivity, attention deficits, and conduct problems among mentally retarded children was addressed using factors of the Conners' Teacher Rating Scale-39 (CTRS-39) and the more recently developed IOWA Conners' inattention/overactivity (IO) and aggression (A) subscales. CTRS-39 ratings were obtained for children of normal intelligence and for mentally retarded children. Differences between the groups were examined as were intercorrelations of the Conners' factors and IOWA subscales. Conduct problems proved to be less strongly associated with hyperactivity and attention deficits among mentally retarded children compared to children of normal intelligence. However, attention problems and conduct problems may be associated with mental retardation in general. Implications of these data and CTRS scoring system recommendations for mentally retarded children are discussed. PMID- 8463500 TI - Narrative abilities in children with attention deficit hyperactivity disorder and normal peers. AB - A story retelling task was used to assess narrative abilities in 30 boys with attention deficit hyperactivity disorder (ADHD) and 30 normally developing boys, matched on age and IQ. Each boy listened to two stories and retold them for another child. Results indicated that the two groups did not differ in their ability to comprehend and extract the main ideas from the stories, but did differ in the production of narratives. Boys with ADHD provided less information overall, and their stories were more poorly organized and less cohesive and contained more inaccuracies. As a result, their stories were often confused and hard to follow. Organization and monitoring of information are functions of executive control. Thus the observed deficits in narrative production in children with ADHD may reflect underlying deficits in executive processes. PMID- 8463501 TI - Parental functioning and children's adjustment in families of divorce: a prospective study. AB - This paper prospectively examined relations between marital status, predivorce parenting practices, and children's adjustment, using data from the New York Longitudinal Study (NYLS). Prospective analyses of children's predivorce adjustment indicated that neither boys nor girls showed more problematic behavior prior to parental separation, and only boys had more difficulties after divorce. However, parents of to-be-divorced families reported more difficulties in childcare practices before divorce than did parents of always-married families. Parenting difficulties in to-be-divorced families were found consistently for boys but not for girls. Results suggest that the difficulties found among boys after divorce may be linked with parenting problems that begin before divorce. PMID- 8463502 TI - Impact of social problem-solving training on aggressive boys: skill acquisition, behavior change, and generalization. AB - This study examined the impact of social problem-solving training on the behavior of five aggressive boys. Acquisition of problem-solving skills and changes in classroom behavior were evaluated using multiple-baseline designs within and across subjects. A generalization-programming procedure to promote the use of problem-solving skills in the natural environment was introduced across children in multiple-baseline fashion. Direct observation and behavior ratings were used to evaluate the treatment. Results indicated that each subject acquired the problem-solving skills at levels comparable to well-adjusted peers. Only one child showed behavioral improvement coincident with problem-solving skill acquisition. Three others showed moderate behavior change after the generalization-programming procedure was introduced. Only one child's gains on teacher ratings were maintained at the 6-month followup. The results suggest that cognitive-behavioral treatment of childrens' aggressive behavior may produce changes of limited magnitude and durability. PMID- 8463503 TI - The prediction of adjustment at age 7 from activity level at age 5. AB - One-hundred and ninety-two children (equally split between boys and girls) were studied when they were 5 years old in two settings, school and home. The children were observed in playgroups and at home, and were rated on activity level by their parents on the Rothbart Child Behavior Questionnaire. At age 7, the children were tested in our laboratory on the Harter Test of Perceived Competence and on an achievement task, and parents filled out the Child Behavior Checklist, the Child Behavior Questionnaire, and the Conners Parent Rating Scale. Home observations of activity level were significantly related to parent ratings of activity level, but not to school observations. Activity level at age 5 was related to parents' ratings of aggression and hyperactivity and to girls' learning problems at age 7. Activity level was not related to the children's self perceived competence, but mothers' rating of high activity level at age 5 was related to low reading comprehension at age 7. PMID- 8463504 TI - Communication styles of children of mothers with affective disorders, chronic medical illness, and normal controls: a contextual perspective. AB - Research has demonstrated impaired parent-child relationships in families with affective disorders. The present study examines the association of children's interactional style during a direct conflict-solving task to both the mother's interactional style and the child's diagnostic status. The sample includes 63 children, ages 8 to 16, of mothers with affective disorders, chronic medical illness, and normal controls. Children's dominant coping style profile (CS) (autonomous, neutral, or critical) was related to their mother's affective style (AS) (benign or negative). Affective disorder in the child at 6-month followup was associated with a critical CS profile at intake, while the child's nonaffective symptomatology was unrelated to CS. Findings indicate that children's affective disturbance is linked to interpersonal deficits in affectively charged situations. Results suggest that the child's CS is more strongly predicted by maternal AS than by either the child's or the mother's diagnostic status. PMID- 8463505 TI - Three forms of stress in Cambodian adolescent refugees. AB - Sixty-nine Cambodian adolescents and young adults were interviewed to determine their experience as children surviving the Pol Pot regime (1975-1979); their first-year experience of resettlement in this country; and their experience of stressful events during the past year. Current DSM-III-R diagnostic status was also determined. A strong relationship between earlier war trauma, resettlement strain, and symptoms of posttraumatic stress disorder (PTSD) was found. In contrast, the strongest relationship with depressive symptoms was found for recent stressful events. These results are discussed in light of current findings from stress and PTSD research. PMID- 8463506 TI - Allergic disorders and attention deficit disorder in children. AB - It has been suggested that children with attention deficit disorder-hyperactivity (ADDH) are likely to show allergic disorders, and that both ADDH and allergic disorders may share a common biological background. In a large sample of children from the general population we found no association between parent, teacher, and self-reports of ADDH behaviors and a history of allergic disorders (asthma, eczema, rhinitis, and urticaria) at ages 9 or 13 years. Similarly, reports of ADDH behaviors at age 13 years were not related to level of atopic responsiveness by skin test or serum IgE levels. Our findings call into question the hypothesis that there is a relationship between ADDH and allergic disorder. PMID- 8463507 TI - Parent reports of child behavior problems: bias in participation. AB - This paper compares the characteristics of 274 children whose parents agreed to provide information about their children's functioning in research with children whose parents did not. Parents had provided permission for child participation in school-approved research. Measures included self-, peer, teacher, and parent ratings. Parents of minority children were less likely to participate than parents of nonminority children. Among nonminorities, children of parent participants were viewed as more socially skilled and liked by their peers; teachers rated them as having less attention problems, less depression, and better academic skills than children of nonparticipating parents. Among minorities, no differences emerged. Implications for research involving the use of parent ratings are discussed. PMID- 8463508 TI - A review of the epidemiology of nutrition and adolescent pregnancy: maternal growth during pregnancy and its effect on the fetus. AB - Maternal growth during adolescent pregnancy and its effects on pregnancy outcome have been a source of controversy. Maternal growth during pregnancy has been difficult to quantify because of the tendency of young and older women to "shrink" in stature with pregnancy. In the Camden Study, maternal growth during pregnancy was monitored with the Knee Height Measuring Device, which measures growth of the lower leg, a body segment less susceptible to "shrinkage." Attempts of other investigators to detect maternal growth during adolescent pregnancy are reviewed here. New data from the Camden Study, also presented, suggest that growing adolescents have infants that weigh less compared to nongrowing adolescents and mature controls (aged 19-29 years). Prior work had suggested that the effects of maternal growth on birth weight were confined to adolescent multiparas. However, with expanded enrollment it was found that infants of growing primiparas and multiparas were both affected. The hypothesis of the competition for nutrients between a still-growing gravida and her fetus is discussed. PMID- 8463509 TI - Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets. AB - Adequacy of nutrient intakes of adolescents with and without phenylketonuria (PKU) and infants and children with and without maple syrup urine disease (MSUD) were assessed using 3-day diet records sorted by disease and by age of the subject. Mean intakes of all nutrients were greater than two-thirds of the Recommended Dietary Allowances (RDA) or Estimated Safe and Adequate Daily Dietary Intakes (ESADDI) for all adolescents studied, with the exception of selenium (Se) in PKU adolescents, which averaged 27.8 micrograms. For adolescents with PKU, > 50% of the RDA or ESADDI for all nutrients was provided by elemental or modified protein hydrolysate medical foods, except for vitamin A in children aged 11-15 years and Se in children 11-18 years. Mean nutrient intakes of all infants and children were greater than two-thirds of the RDA or ESADDI for all nutrients except Se in MSUD children aged 1-11 years, where intakes ranged from 6.4 to 13.2 micrograms (21-66% of the RDA). The medical foods provided for most of the RDA and ESADDI recommendations, with the exception of Se in MSUD children. PMID- 8463510 TI - Histidinemia: a biochemical variant or a disease? AB - Histidemia, first described by Ghadimi in 1961, is caused by a defect in histidase. The defect results in elevated urinary excretion of histidine and its transamination products, and in high blood histidine. Blood histidine levels in histidinemic patients range from 290 to 1420 microM (normal 70-120 microM). The clinical picture of histidinemia varies from complete normality to severe retardation, with many patients being asymptomatic. No correlation has been found between clinical and biochemical data. Most reported cases have been identified in newborn screening programs. Frequency of histidinemia ranges from 1 in 8000 (Japan) to 1 in 37,000 (Sweden). Histidinemia is inherited as an autosomal recessive trait. Maternal histidinemia is believed to be benign. Studies in animal models have shown similar metabolic changes in animals and humans, but clinical changes differ. Histidinemia may be treated with a low-histidine diet, which reduces elevated histidine levels, although in most cases no improvement of clinical symptoms has been observed. PMID- 8463511 TI - Plasma lipid physical properties in swine fed margarine or butter in relation to dietary magnesium intake. AB - Plasma lipids obtained from swine which had been fed butter or margarine at two dietary magnesium (Mg) levels indicated that the level of dietary Mg was more significant to plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels than was the presence of butter or margarine. At 270 mg Mg/kg, which is considered adequate for swine, there was a significant difference in the plasma TC between swine fed margarine and those fed butterfat (105 and 126 mg %, respectively). Plasma LDL-C was higher in swine fed butter than in those fed margarine (88 and 71 mg %, respectively). In swine fed an additional 247 mg Mg/kg, however, there was no significant difference in plasma TC between those fed margarine or butter. Although at 247 mg Mg/kg, however, there was no significant difference in plasma TC between those fed margarine or butter. Although at 247 mg Mg/kg plasma LDL-C was higher in swine fed margarine and HDL-C was higher in those fed butter, there were no significant differences in the order parameters of LDL and HDL. Studies in which the influences of dietary fats on plasma cholesterol were first noted were carried out on liquid diets deficient in Mg. Mg, a cofactor in the enzymes involved in desaturation of saturated fatty acids, is also necessary in desaturation of linoleic to arachidonic acid. PMID- 8463512 TI - Dietary magnesium affects susceptibility of lipoproteins and tissues to peroxidation in rats. AB - Magnesium (Mg)-deficient and control diets were pair-fed to weanling Wistar rats for 8 days. Plasma lipoproteins were separated into various density classes by sequential preparative ultracentrifugation. The extent of lipid peroxidation was measured in terms of thiobarbituric acid reactive substances in lipoproteins and tissue homogenates before or after iron-induced lipid peroxidation. Hyperlipemia in Mg-deficient rats was accompanied by increased oxidation of very-low-density lipoproteins and low-density lipoproteins. Moreover, very-low-density lipoproteins and high-density lipoproteins from Mg-deficient rats were more susceptible to oxidative damage following iron incubation. Mg deficiency increased lipid peroxidation in liver, heart and skeletal muscles. Their homogenates were more susceptible to in vitro peroxidation. Mg deficiency has been discussed as a possible contributory factor in the development of cardiovascular disease and was associated with tissue damage and membrane alteration. These results demonstrate for the first time that Mg affects the susceptibility of lipoproteins to peroxidation and suggest that the mechanism responsible for the pathological consequences of Mg deficiency may be mediated by lipid peroxidation products. PMID- 8463513 TI - Cataract: relationship between nutrition and oxidation. AB - Opacification of the lens, or cataract, is causally related to the precipitation of proteins or other constituents upon aging. Proteins in the lens are unusually long lived and are subject to extensive damage, including (photo)oxidation. Accumulation of damaged proteins also appears to be due in part to attenuated activity of some proteolytic pathways, which in younger tissue may serve to identify and remove such moieties. The damaged proteins accumulate, aggregate, and precipitate. Compared with other health problems, surgery to remove cataract and related visits to physicians consume the largest proportion of the Medicare budget, i.e., $3.2 billion annually in the United States. The situation is exacerbated in many parts of the world where there is a dearth of ophthalmologists to perform the required number of procedures. Historically efforts to delay cataract assumed a low profile in ophthalmologic research. Recent data, however, indicate that consuming elevated levels of antioxidants such as ascorbate, carotenoids, and tocopherol is associated with delayed development of various forms of cataract. The same beneficial relationship to vision pertains to plasma antioxidant status and to fruit and vegetable intake. Thus, it seems that assuring optimal antioxidant intake can extend lens function. It has been estimated that in the United States over half of the cataract extractions and associated costs would be obviated if cataract could be delayed by 10 years. The data reviewed indicate that optimizing nutrition will help achieve that objective. PMID- 8463514 TI - Vitamin-mineral supplement use and nutritional status of athletes. AB - Dietary, anthropometric, and chronic disease risk factors (CDRF) including blood lipids and blood pressure (BP), were measured in 91 vitamin-mineral supplement users (SU) and nonusers (NU) representing a wide range of athletic interests. Supplements were used by 46 (51%) subjects; 100% of female athletes and 51% of male athletes used supplements while none of a group of 15 control female subjects currently used supplements. Both dietary intake and energy expenditure were measured using 7-day records. Adiposity was determined from body weight, body mass index, and skinfolds. Total cholesterol, high-density lipoprotein cholesterol, serum ferritin, hemoglobin, hematocrit, zinc, copper, and vitamin C were based on 12-hour fasting blood samples. Dietary intake (excluding supplements) for SU tended to be greater than NU for vitamin C, thiamin, riboflavin, niacin, B6, B12, folate, calcium, iron and magnesium. Plasma vitamin C levels were significantly higher among SU than NU of both gender groups (p < 0.05). Although SU may exhibit additional healthy lifestyle practices, lipid profiles for many of these athletes were unfavorable with regard to CDRF. PMID- 8463515 TI - Wheat gluten-based diet retarded ethanol metabolism by altering alcohol dehydrogenase and not carnitine status in adult rats. AB - The objective of this study was to determine the effect of a lysine-deficient diet on carnitine status in adult rats and subsequently on ethanol metabolism. Adult male rats were fed either the AIN-76 diet (NS), the AIN-76 diet with wheat gluten (WG) replacing casein, the WG diet plus 0.8% L-lysine (LS), or the LS diet plus 0.5% L-carnitine (CS) for 30 days. On the 31st day the rats were given an oral dose of ethanol and blood-ethanol concentrations (BEC) were monitored for the next 8 hours. One week later the rats were given a second dose of ethanol and urine was collected until killed, 3 hours post-ethanol administration (PEA). Besides growth retardation and hypoproteinemia, BEC were significantly elevated in the WG group compared to the other group at hours 3-8 PEA. There were no significant differences in BEC between the LS and CS groups; however, their BEC were significantly higher than that of the NS group. The BEC were inversely related to liver alcohol dehydrogenase (ADH) activities which were significantly lower in WG, LS and CS groups than in the NS group. Plasma, liver and urine carnitine values were significantly higher in the CS group than in the NS, WG and LS groups, wherein the values were similar. It is concluded that the WG diet reduced ADH activity and attenuated ethanol metabolism without significantly altering blood, liver and urinary carnitines in the adult rat. PMID- 8463516 TI - Low serum folic acid levels in a nursing home population: a clinical experience. AB - Four hundred fifty-five residents of the Wisconsin Veterans Home had fasting serum specimens obtained for folic acid as part of standard practice. Twenty-nine percent were taking folic acid supplements. Six percent (n = 28) were taking phenytoin, a folate antagonist. No resident receiving a folate supplement (400 mcg/day) had a low serum folic acid level. This finding may be important for practitioners selecting a dose of folic acid for nursing home patients. Of the 325 residents not receiving a folate supplement, nine (3%) had low folic acid levels (< 2.5 ng/mL). Two of the nine were receiving phenytoin. Five were characterized by staff as eating well. As low serum levels are preventable with a multivitamin, we believe that supplementation with a multivitamin containing 400 mcg folic acid/day should be considered in nursing home residents. PMID- 8463517 TI - Negative findings for use of coconut water as an oral rehydration solution in childhood diarrhea. AB - This study reports the chemical composition of coconut water during its maturation. Composition was measured at 5, 6, 7, 8, 9, 10, 11 and 12 months maturation. Concentrations of sodium and glucose, and the osmolality values showed great variation throughout maturation. The concentration of sodium remained constant between the 5th and 7th months (mean 2.9 mEq/l), but increased after the 8th month (mean 12.5 mEq/l). The concentration of glucose remained constant between the 5th and 8th months (mean 3392.4 mg%), but abruptly decreased after the 9th month (mean 820 mg%). Osmolality followed the variation of the glucose concentration averaging 377.3 mOsm/l up to the 8th month, then decreasing to 310.3 mOsm/l after the 9th month. This study showed great variability in coconut water composition during maturation of the fruit. In no instance did the coconut water contain sodium and glucose concentrations of potential value as an oral rehydration solution. PMID- 8463518 TI - Recent issues related to nutrition during pregnancy. AB - In July 1990, new guidelines for nutrition during pregnancy were published by the National Academy of Sciences. The Subcommittee on Weight Gain During Pregnancy revised the weight gain recommended for pregnancy. During the process of developing new recommendations, the subcommittee considered several factors that might help to determine the appropriate weight gain for an individual pregnant woman. Some of these factors include demographic and biological changes that might influence the effect of weight gain. Clinical issues that must be considered in implementing the weight gain recommendations include the importance of accurate weight and height measurement, categorizing the woman's weight for height, determining rate of gain at different times during pregnancy, and evaluating the significance of deviations from the expected weight gain pattern. A review of prior studies reveals that body composition changes, which might be important to consider in conjunction with weight changes, have not been well studied. Data are presented from a current study that indicates the problems encountered if traditional methods of body composition measurement are used during pregnancy. PMID- 8463519 TI - The importance of dietary protein in healing pressure ulcers. AB - OBJECTIVE: To determine the effect of dietary protein on healing of pressure ulcers in malnourished patients. DESIGN: Nutritional intervention trial with the non-randomized assignment of patients by pressure ulcer stage and bed type. SETTING: Long-term care facility. PATIENTS: Twenty-eight malnourished patients (age = 72 +/- 18 years, mean +/- SD) with a total of 33 truncal pressure ulcers. Nine patients had stage II ulcers, eight had stage III ulcers, and 16 had stage IV ulcers. METHODS: Patients received liquid nutritional formulas as tubefeedings or meal supplements containing either 24% protein (61 g protein/L; n = 15) or 14% protein (37 g protein/L; n = 13) for 8 weeks. RESULTS: There was a significant decrease in total truncal pressure ulcer surface area of the 15 patients in the 24% protein group (-4.2 +/- 7.1 cm2, P < 0.02), but not in the 13 patients in the 14% protein group (-2.1 +/- 11.5 cm2, P = NS). The change in total ulcer area correlated with both dietary protein intake per kg body weight (rs = -0.50, P < 0.01) and caloric intake per kg body weight (rs = -0.41, P < 0.03). The decrease in stage IV ulcer area in eight patients in the 24% protein group (-7.6 +/- 5.8 cm2, P < 0.02) was significantly greater (P < 0.05) than in eight patients in the 14% protein group (-3.2 +/- 16.4, P = NS). In these 16 patients, the decrease in ulcer size also correlated with dietary protein intake per kg body weight (rs = 0.63, P < 0.01). CONCLUSION: High protein diets may improve the healing of pressure ulcers in malnourished nursing home patients. PMID- 8463520 TI - Treatment of vasculogenic sexual dysfunction with pentoxifylline. AB - OBJECTIVE: To evaluate the use of pentoxifylline to treat impotence in men with mild to moderate penile vascular insufficiency. DESIGN: Double-blind randomized clinical trial. SETTING: Sexual Dysfunction Clinic at VA Medical Center, Sepulveda, CA. PARTICIPANTS: Convenience sample of couples. INTERVENTION: Twelve weeks of treatment with placebo or 400 mg tid of pentoxifylline. MEASUREMENTS: (1) Report of patient verified by partner as to number of coital episodes per month; (2) penile-brachial pressure index determinations. RESULTS: Pentoxifylline therapy regularly increased the PBPI in impotent men in comparison with the placebo, frequently into the normal range. Pentoxifylline therapy was particularly useful in restoring the PBPI in men with the pelvic steal syndrome; six of seven such subjects improved into the normal range. During the pentoxifylline treatment period, in contrast with the control period, nine men were able to reestablish coital function and three had no improvement. Six couples did not attempt intercourse despite a professed interest in sexual activity; however five out of the six men experienced erections during episodes of fantasy or attempts at masturbation during treatment. There were no complications of therapy. CONCLUSIONS: These promising preliminary results suggest a well tolerated alternative therapy for erectile dysfunction in patients with mild to moderate penile vascular disease. PMID- 8463521 TI - L-deprenyl in the treatment of mild dementia of the Alzheimer type: preliminary results. AB - OBJECTIVE: To examine the short-term cognitive and behavioral effects of L deprenyl in persons with mild dementia of the Alzheimer type (DAT) over a 2-month period. DESIGN: A 15-month randomized, double-blind, placebo-controlled trial using a parallel-group design. This report deals with the first 2 months of the trial. PARTICIPANTS: 39 subjects with mild DAT (CDR 1) selected using NINCDS ADRDA criteria. MEASURES: A battery of neuropsychological tests and clinical rating scales. RESULTS: The placebo and L-deprenyl subjects were similar at baseline on the clinical and neuropsychological tests. There was no evidence of a L-deprenyl effect on any clinical or neuropsychological measures after 2 months. CONCLUSION: L-deprenyl did not have a measurable impact on behavior or cognitive function over a 2-month period in this group of subjects with mild DAT. PMID- 8463522 TI - The dark side of incontinence: nighttime incontinence in nursing home residents. AB - OBJECTIVE: To describe the characteristics of nighttime urinary incontinence in a sample of nursing home (NH) residents. DESIGN: Prospective descriptive study of a convenience sample of incontinent NH residents. SETTING: Four NHs. PARTICIPANTS: 136 incontinent NH residents. MEASUREMENTS: Frequency and volume of incontinent and continent voids for three 10-hour daytime and three 10-hour nighttime data collection periods. RESULTS: The frequency of nighttime incontinence was the same as during the day, but the volume of nighttime incontinent voids and total nighttime volume were higher than during the day. There was substantial between- and within-subject variability in volumes, but the distribution of ratios of night/total volumes approximated a normal curve. Diuretic use was associated with relatively low nighttime volumes. CONCLUSION: About one-quarter of the NH residents we studied produced substantially more urine at night than during the day. Several medical, behavioral, and environmental approaches should be considered for reducing the frequency and volume of nighttime incontinence in this population. PMID- 8463523 TI - Influence of age on measurement of health status in patients undergoing elective surgery. AB - PURPOSE: To assess the influence of age on the relationships between global measures of health and specific health dimensions. DESIGN: Cross-sectional cohort study. SETTING: University tertiary care hospital. PATIENTS: Patients older than 50 years admitted for major elective non-cardiac surgery. MEASUREMENTS: Consenting patients underwent preoperative evaluations including a medical history, physical examination, and administration of health status assessment instruments. Global health status was measured with the Medical Outcomes Study Short Form (SF-36) and with a 0 to 100 verbal measure of global health. Specific health dimensions (physical function, role function, social function, mental health, energy and fatigue, and pain) were measured using the SF-36. Subjects also completed a second validated measure of physical functioning, the Specific Activity Scale (SAS). RESULTS: Although patients aged > 70 years (n = 276) had poorer role function, energy, and fatigue scores and poorer physical function on both the SF-36 and SAS than younger patients (n = 469) (P < 0.05), they had similar overall health perception. In the entire population, global health status as measured with the SF-36 health perception scale had the greatest correlation with the energy and fatigue scale (r = .45), correlated moderately with mental health (r = .35), social function (r = .32), and physical function (r = .33), and correlated less well with the surgically remediable dimension of pain (r = .23). However, correlations of global health perception with pain and global health perception with role functioning were significantly (P < or = 0.05) lower in older patients when compared with subjects 70 years or younger (r = .13 vs .28 and r = .19 vs .33, respectively). CONCLUSION: Despite poorer role function, poorer energy and fatigue scores, and poorer physical function, elderly persons have similar global health perception when compared with younger individuals. These data indicate that global health perception may be determined by different factors in the elderly or that the elderly have fundamentally different expectations of what their global health status should be. Our findings emphasize the importance of multidimensional scales when evaluating quality of life because, particularly in the elderly, the use of global measures alone may not reflect critically important dimension-specific impairments in health. PMID- 8463524 TI - Utilization of cardiopulmonary resuscitation in nursing homes in one community: rates and nursing home characteristics. AB - OBJECTIVE: To determine the rate of cardiopulmonary resuscitation use among all nursing homes in a large urban area, to examine CPR use over time, to discover whether CPR use varies among nursing homes, and to describe characteristics of patients undergoing CPR. DESIGN: Retrospective survey. SETTING: Nursing homes in a large urban area. PARTICIPANTS: One hundred ninety-six nursing home residents of 68 nursing homes underwent cardiopulmonary resuscitation over a 4-year period (1986-1989). Over this time there were 9,486 deaths in these homes, which comprised 10,252 beds. MEASUREMENTS: The CPR:death ratio was determined for each facility. The ratio was analyzed over time and by type of facility (eg, proprietary, non-profit, size of facility). The ratio was also examined among facilities with variable death rates. Patients undergoing CPR are described. RESULTS: The ratio of CPR:death over the 4-year period was 0.02. CPR:death ratio was higher (0.03) for the proprietary homes compared with the non-profit homes (0.01) P < 0.0001. A significant downward trend of CPR:death was noted over the study period for the non-profit homes; no such trend was noted in the proprietary homes. Size of nursing home did not influence the rate of CPR use. Homes with greater numbers of deaths per bed had a lower utilization of CPR. Patients undergoing CPR were old, frail, and had multiple medical problems. CPR attempts were frequent around the time of nursing home admission. CONCLUSION: The utilization of CPR in nursing homes is quite low. Non-profit homes utilize CPR less than proprietary homes. Nursing homes with the highest numbers of deaths per bed utilize CPR less than homes with lower numbers of deaths per bed. Nursing home residents receiving CPR are quite old, have multiple illnesses, and are impaired. PMID- 8463525 TI - A practical equation to predict resting metabolic rate in older females. AB - OBJECTIVE: To develop a practical and accurate age-specific equation for predicting resting metabolic rate (RMR) in older women and, thereafter, to cross validate existing equations for predicting RMR in older females. DESIGN: Cross sectional validation study. SETTING: General Clinical Research Center. PARTICIPANTS: A convenience sample of 75 healthy older women (age 50-81) free of significant cardiovascular or any other non-cardiac disease that may affect cardiovascular function or metabolic rate. MEASUREMENTS: All 75 volunteers were characterized for resting metabolic rate (RMR), body composition, anthropometrics, physical activity, and energy intake. RESULTS: A practical equation for predicting RMR in older women using easily measured variables was: [RMR (kcal/d) = 7.8 (weight,kg) + 4.7 (standing height, cm) -39.5 (menopausal status; 1-3) + 143.5]. These variables accounted for 59% (R2) of the variation in RMR and predicted RMR within +/- 66 kcal/d. When five previously published equations were applied to our sample of older women to predict RMR, individual predicted values deviated by -31% to 20% from the measured value. CONCLUSION: We offer a practical equation to predict RMR in healthy older women based on a measure of body weight, standing height, and menopausal status. PMID- 8463526 TI - The role of prognostic scores in targeting stroke rehabilitation in elderly patients. AB - OBJECTIVE: To determine the validity of clinically derived prognostic scores in targeting stroke rehabilitation in elderly patients. DESIGN, SETTING AND PARTICIPANTS: One-year prospective cohort study in 96 hospitalized stroke patients over 75 years of age from a well defined geographical area. MEASUREMENTS: Edinburgh prognostic score (incorporating measures of motor deficit, proprioception, and power), Orpington prognostic score (Edinburgh score modified to include a measure of cognition), and Barthel ADL scores were measured at 1, 2, and 4 weeks after stroke. These scores were correlated with outcome and patients' Barthel ADL score at discharge or at 16 weeks if still in hospital. RESULTS: Edinburgh prognostic score measured at 2 weeks correlated significantly with Barthel ADL score at discharge or at 16 weeks (r2 = 0.57, P < 0.001), and Orpington prognostic scores showed greater correlation (r2 = 0.89 vs 0.57), especially in patients with dementia (r2 = 0.81 vs 0.39). Barthel ADL scores at 2 weeks showed a weak correlation with Barthel ADL scores at discharge or 16 weeks (r2 = 0.58). Patients with Orpington Score < 3.2 were discharged within 3 weeks of stroke, whereas those scoring > 5.2 required long-term care. Most patients (90%) with Orpington Score of 3-5 were eventually discharged home although this was not always apparent on initial clinical assessment at the time of admission. CONCLUSIONS: The Orpington score when assessed at 2-weeks post-stroke is a useful prognostic indicator with special suitability for the elderly and may help to select patients most likely to benefit from stroke unit rehabilitation. PMID- 8463527 TI - Sensory impairment and quality of life in a community elderly population. AB - OBJECTIVE: To determine the association between quality of life measures and sensory impairment in aged individuals living at home. DESIGN: Survey SETTING: A community survey, carried out in the historical center of a town in Northern Italy. PATIENTS: 1191 non-institutionalized elders (age 70-75 years). MEASUREMENTS: Comprehensive QOL questionnaire, free-field voice testing, and Snellen eye chart. RESULTS: Single sensory impairments (either visual or auditory) were significantly and independently associated with increased risk for depression (odds ratio: 2.3, 95% confidence interval: 1.5-3.4; OR:1.8, CI:1.1 2.7, respectively) and decreased self-sufficiency in daily living activities (OR:1.7, CI:1.1-2.6; OR:2.1, CI:1.4-3.2, respectively). Visual dysfunction, but not hearing dysfunction, was independently associated with lower social relationships (OR:2.0, CI:1.3-3.1). CONCLUSION: The quality of life of community dwelling elderly people is significantly linked to sensory impairment, which can be detected through simple physical examination. Mood level and social relationships are particularly affected by visual impairment, whereas self sufficiency in daily living is more strongly related to hearing impairment. PMID- 8463528 TI - Drug use patterns of persons with Alzheimer's disease and related disorders living in the community. AB - OBJECTIVE: To describe drug use patterns by persons with Alzheimer's disease, multi-infarct dementia, and mixed Alzheimer's disease and multi-infarct dementia. DESIGN: Multicenter, patient registry. SETTING: Community-living persons evaluated in primary care, geriatric, and Alzheimer ambulatory settings. PARTICIPANTS: Of the 930 persons in three diagnostic categories, there were 671 with probable or possible Alzheimer's disease by NINCDS/ADRDA criteria or Alzheimer's disease by DSM-III-R criteria, 162 multi-infarct cases by DSM-III-R criteria, and 97 mixed cases by DSM-III-R criteria. In each diagnostic category, 65% were women, and the majority were 70 years or older. MEASUREMENTS: The average number of all prescription and non-prescription drugs and selected therapeutic categories by age, sex, diagnosis, and mini-mental status score at the time of diagnosis or evaluation. RESULTS: Alzheimer patients average 2.3 drugs compared with multi-infarct (4.3; P < 0.0001) and mixed (3.7; P = 0.002) patients, and their pattern of drug use was different when stratified by therapeutic categories and drug classes. Drug use increased with age, and women used significantly more drugs than men in all three diagnostic categories. Women with Alzheimer's disease used significantly more cardiovascular drugs than men with Alzheimer's disease (P < 0.05). The lower the mini-mental status score in patients with any dementia, the greater the mean number of central nervous system agents used. The higher the mini-mental status score in a patient with multi infarct or mixed dementia, the greater the use of cardiovascular drugs. CONCLUSION: Drug use by Alzheimer patients was lower than in multi-infarct and mixed patients, primarily due to a lower prevalence of cardiovascular drugs. PMID- 8463529 TI - Exogenous calciferol (vitamin D) and vitamin D endocrine status among elderly nursing home residents in the New York City area. AB - OBJECTIVE: To determine the role and relative importance of sources of exogenous calciferol (vitamin D) in maintaining vitamin D endocrine status in the mid winter and early spring in a representative sample of institutionalized elderly persons in the New York City area. DESIGN: Cross-sectional survey. SETTING: A privately-run urban nursing home and the long-term care unit of a suburban public hospital. PARTICIPANTS: Residents aged 60 years and older scheduled for a routine annual physical examination and an additional group of individuals ascertained by random sampling. Those with a history of anti-convulsant or glucocorticoid use, liver disease, chronic renal disease (or serum creatinine > 1.5 mg/dL), parathyroid disease, Paget's disease, gastric surgery, or pharmacological vitamin D use were excluded. Of 301 sampled individuals, 221 were found eligible to participate, and 109 were successfully enrolled. RESULTS: The average vitamin D intake was 379 IU/day (range 55-1006 IU/day) and total vitamin D intake was below the Recommended Dietary Allowance in 16% of subjects. Fifty percent of total vitamin D intake came from fortified milk, and 26% came from vitamin supplements. Vitamin supplement use was not associated with low dietary intake. Among subjects taking a supplement containing 400 IU/day, none had serum calcidiol levels below 15 ng/mL, while among subjects with vitamin D intake between 200 and 400 IU/day, 46% had serum calcidiol levels below 15 ng/mL and 14% had calcidiol levels below 10 ng/mL. Vitamin D intake from non-supplement sources (but not from supplements) appeared to have a negative association with serum calcitriol levels. CONCLUSIONS: Many nursing home residents may require vitamin supplements in order to achieve optimal levels of calciferol replacement. The choice of a vehicle for calciferol replacement may affect calcitriol levels. PMID- 8463530 TI - Interarm blood pressure difference in acute hemiplegia. PMID- 8463531 TI - Sudden death and resisted mechanical restraint: a case report. PMID- 8463532 TI - The menopause: health implications and clinical management. AB - OBJECTIVE: To review the anatomy, physiology, clinical symptoms, long-term health effects, and treatment of the menopause and climacteric syndrome, with a special emphasis on features, such as incontinence, particularly relevant to geriatric medicine. DATA SOURCES: English-language publications on menopause and the climacteric. STUDY SELECTION: Articles and books containing recent information pertinent to the topics covered. Studies in human subjects were given priority, but primate studies that amplify physiologic concepts are included. DATA SYNTHESIS: Due to increased longevity, the average US woman will spend one-third of her life as a postmenopausal individual. Anatomic and physiologic changes associated with the peri- and postmenopausal state include hot flushes, genitourinary atrophy, and bone loss. Possible correlates of the menopausal transition and postmenopause include affective changes and unfavorable alterations in lipoproteins and other cardiac risk factors. Clinical correlates of these changes can include incontinence, sexual dysfunction, increased risk of fracture, dysphoric mood, and increased risk of cardiovascular disease. Formal indications for estrogen therapy are hot flushes, genital atrophy, and osteoporosis prevention; other common clinical uses are reviewed. Non contraceptive estrogens can be administered orally, transdermally, vaginally, or by injection. Each route and preparation has some unique features with respect to actions and side effects. Progestins, in adequate doses, protect against the unwanted side effect of endometrial hyperplasia; alternatives to progestin use are presented. Non-hormonal alternatives for some peri- and postmenopausal symptoms are described. CONCLUSIONS: A discussion of the menopause and the benefits and risks of hormone therapy should be part of the routine health care of older women. Since the use of hormone therapy is elective, health care providers must elicit the goals, needs, and preferences of each patient, supply her with relevant information, and serve as a facilitator of her individual decision. PMID- 8463533 TI - Functional status care categories and national health policy. AB - Our society clearly needs to set limits on health care. The United States health care delivery system is the fourth largest economy in the world, yet its inflation continues to grow at twice the normal rate of other products and services. The inefficiencies are built in in such a way that while intensive care beds are plentiful, and very expensive, 37 million Americans cannot gain access to health care because they are either uninsured or underinsured. It is estimated that this figure will approach 39 million by the end of the decade. Since many of these individuals are young, the problem, it is said, has no real practical consequences because the young are relatively healthy. Yet evidence exists that the uninsured and underinsured receive poorer care than covered individuals. This and other inequities in the system have led many thinkers like Leonard Fleck to ask how just we must be in society. The answer to this question would presumably help us determine the lengths we must go in correcting the inequities. Even if the peace-dividend emerges from the new political events around the world, and we are able to spend more of our money on health care, our resources are not a bottomless pit. If need alone drives the system, just performing open-heart surgery on everyone who needs it would cost more than the annual budget itself. Virtually everyone agrees, then, that escalating health care costs are a moral problem because justice is involved, a political problem because public interest is involved, and that limits must be set that are moral and public. PMID- 8463534 TI - How many physicians will be needed to provide medical care for older persons? Physician manpower needs for the twenty-first century. AB - To estimate the number of full-time-equivalent (FTE) physicians and geriatricians needed to provide medical care in the years 2000 to 2030, we developed utilization-based models of need for non-surgical physicians and need for geriatricians. Based on projected utilization, the number of FTE physicians required to care for the elderly will increase two- or threefold over the next 40 years. Alternate economic scenarios have very little effect on estimates of FTE physicians needed but exert large effects on the projected number of FTE geriatricians needed. We conclude that during the years 2000 to 2030, population growth will be the major factor determining the number of physicians needed to provide medicare care; economic forces will have a greater influence on the number of geriatricians needed. PMID- 8463536 TI - The future practice of long-term care. PMID- 8463535 TI - Who cares for Missouri's Medicaid nursing home residents? Characteristics of attending physicians. AB - OBJECTIVE: To describe the characteristics of physicians attending Medicaid recipients in Missouri's certified nursing homes (NH). DESIGN: Retrospective survey of multiple data sources. SETTING: Missouri's certified nursing homes. PARTICIPANTS: 1,339 physicians attending 22,452 Medicaid recipients. MEASUREMENTS: Physician characteristics were determined by reviewing a roster of medical directors of NHs compiled by the Missouri Department of Social Services' Division of Aging and physician directories compiled by the Missouri State Board of Registration for the Healing Arts, the AMA, the AOA, the ABFP, and the ABIM. Physician clinical activity was determined by examining NH inspection of care reports compiled by the Missouri Department of Social Services' Division of Aging. RESULTS: Each physician attended a mean of 16.8 and a median of six Medicaid recipients in the nursing home. The skewed distribution is reflected by 426 (31.8%) of the physicians attending only one or two residents, and 28 (2.1%) of the physicians attending 100 or more residents. Twenty-seven percent of the state's licensed osteopaths (DOs, 362) attended nursing home patients, compared with 11% of allopathic physicians (MDs, 977). Significantly more DOs than MDs attended more than the median number of patients (57% vs 45%, P < 0.001). Half were attended by the 605 (45%) physicians without board certification. Of those who were board certified, family physicians were more likely to include Medicaid nursing home patients in their practices than internists (43% vs 18%, P < 0.001). Physicians licensed for 11 to 20 years and rural physicians had the heaviest patient loads. CONCLUSIONS: Many doctors are caring for very few nursing home residents while a few doctors may be caring for too many patients. In addition, half the Medicaid recipients residing in Missouri's nursing homes in 1988 were attended by physicians without board certification, and almost one-third were attended by physicians who may be retiring between 2000 and 2010. PMID- 8463537 TI - Geriatric medicine: a true primary care discipline. PMID- 8463538 TI - When the limits are not their own: why the elderly must participate in health care reform. PMID- 8463539 TI - Drinking in the elderly. PMID- 8463540 TI - Screening for depression. PMID- 8463541 TI - Statistical impact of truncated sampling or alteration of administration: the case of the Geriatric Depression Scale. PMID- 8463542 TI - OBRA-1987 nursing home regulations. PMID- 8463543 TI - Caregiver stress. PMID- 8463544 TI - Acute stooped position in elderly with Alzheimer's disease. PMID- 8463545 TI - Magnesium and hypertension. PMID- 8463546 TI - Plasma 3 alpha-androstanediol glucuronide in precocious adrenarche. AB - The aim was to study 3 alpha-androstanediol glucuronide (3AG) plasma levels and its relationship with 5-ene and 4-ene steroids in children with the benign form of precocious pubarche (precocious adrenarche). Sixty-five children with precocious adrenarche (PA), aged 3.6-8.2 yr (55 girls and 10 males) and 15 normal age-matched children were studied. We evaluated plasma androstenedione (A), dehydroepiandrosterone (DHA), its sulfate (DHA-S), testosterone (T), dihydrotestosterone (DHT), its glucuronide (DHTG), 3 alpha-androstanediol (3Ad) and its glucuronide (3AG) in all subjects. All androgens are expressed as mean +/ SD. We found significantly higher plasma levels not only in glandular androgens but also in peripheral androgens (A, 2.4 +/- 1.5 nM vs 0.79 +/- 0.46 nM, p < 0.001; DHA, 9.8 +/- 4.9 vs 2.7 +/- 0.76 ng/dl, p < 0.001; DHA-S, 3.4 +/- 2 microM vs 2.4 +/- 0.65 microM, p < 0.05; T, 0.74 +/- 0.5 nM vs 0.4 +/- 0.1 nM, p < 0.001; DHT, 0.36 +/- 0.13 nM vs 0.12 +/- 0.05 nM, p < 0.001; 3Ad, 0.13 +/- 0.1 nM vs 0.054 +/- 0.03 nM, p < 0.001; DHTG, 0.5 +/- 0.3 nM vs 0.26 +/- 0.09 nM p < 0.01). As far as the plasma 3AG levels are concerned we found significantly higher values in PA with respect to controls (1.17 +/- 0.7 nM vs 0.61 +/- 0.04 nM, p < 0.01), suggesting that 3AG may be considered a marker of skin androgen utilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463547 TI - Acromegalic cardiopathy: a left ventricular scintigraphic study. AB - In order to study "acromegalic cardiomyopathy", cardiac function was examined, using gated radionuclide ventriculography, in 18 acromegalic patients and 21 control subjects with no clinical evidence of cardiac involvement. In these acromegalic subjects, while the Ejection Fraction (EF) did not appear to be significantly different, the Peak Filling Rate (PFR) was reduced while the Time to Peak Filling Rate (TPFR) resulted significantly greater than in control subjects. These findings indicate that chronic growth hormone (GH) hypersecretion, as observed in acromegaly, deteriorate the cardiac ventricular relaxation (diastolic phase) while it has no influence on contractility (systolic phase). PMID- 8463548 TI - Smoking--a risk factor for hypothyroidism. AB - Smoking is associated with a spectrum of disorders. Recent reports have shown decreased serum concentrations of thyrotropin in euthyroid smokers, and there is an association between smoking and development of goiter (toxic and euthyroid). In a 12-year follow-up of a randomly selected sample of women we found a strong association between smoking at the time of initial screening and later development of hypothyroidism, the relative risk for a female smoker to develop hypothyroidism being 3.9 (95% confidence interval 1.6-9.1). There was, however, no association between smoking habits at the end of the follow-up and hypothyroidism. This indicates that several women who developed hypothyroidism may have done so in association with a change in smoking habits. PMID- 8463549 TI - Oxandrolone in constitutional delay of growth: analysis of the growth patterns up to final stature. AB - In order to evaluate the effects of low-dosage, 6-12 months course of oxandrolone treatment in constitutional delay of growth, we compared the growth responses on treatment, the pattern of sexual development and pubertal growth events, up to final stature of 11 prepubertal boys, aged 10.6-14.1 yr, with those of 11 prepubertal, age-matched untreated controls. Treatment caused a significant increase of height velocity, from 4 to 9 cm/yr, and a significant acceleration of bone maturation, without affecting the timing of onset of puberty, the progression of sexual development or the onset of pubertal growth spurt. On the other hand, oxandrolone induced an earlier skeletal growth arrest but did not affect the expected final height. Treated boys showed an adult stature not significantly different from that of control subjects. Our data suggest that 6 months-1 year, low dosage oxandrolone treatment in constitutionally delayed growth has no significant effect on the pattern of pubertal growth, nor on the rate of sexual maturation or on final height. PMID- 8463550 TI - Metastatic thyroid carcinoma of the adrenal gland. AB - Follicular thyroid carcinoma may spread distant metastases in sites such as bone, lung and brain. In our series of 448 patients with follicular thyroid carcinoma, distant metastases were present in 25% of cases. We report here a case of follicular thyroid carcinoma with a single metastasis at the right adrenal gland, that was found 12 years after total thyroidectomy and radioiodine therapy. Chest X ray, neck and liver echography and total body scan (TBS), performed after radioiodine therapy, were negative. During hormone therapy, serum thyroglobulin (Tg) levels were less than 1 ng/ml until 1990, and then Tg progressively increased in eighteen months up to 149 ng/ml. A new TBS was negative. At computer tomography a node at the right adrenal gland was found. The patient underwent adrenalectomy and histology showed a metastatic follicular thyroid cancer with Hurthle cells. After 1 and 5 months from surgery Tg serum levels were 0.9 ng/ml. This case shows once again the importance of Tg serum levels during follow-up of differentiated thyroid cancer. PMID- 8463551 TI - The effect of epidermal growth factor in human granulosa cells varies with follicle size. AB - EGF decreases aromatase activity and stimulates the proliferation of granulosa cells. To determine if EGF affects follicles of different maturity differently, human granulosa cells obtained from 6 patients at the time of IVF were pooled according to size and cultured in serum free medium with or without EGF. Estrogen production at 72 h was determined by measuring tritiated water formed in a 1-h culture with 1 beta [3H] androstenedione. The change in estrogen production with EGF was compared for cells from the smallest and largest follicles for each patient. Estrogen production in response to EGF decreased with increasing follicular size in all six observations. EGF may mediate luteinized granulosa cell aromatase activity in vivo, and may be a factor responsible for the relative decline in estrogen production in the preovulatory follicle. PMID- 8463553 TI - The behavioral syndrome induced by adreno corticotropic hormone in rats is prevented by Ca++ channel blockade. AB - The most typical signs (stretchings, yawnings, penile erections, excessive grooming) of the behavioral syndrome induced in rats by the intracerebroventricular administration of ACTH- (1-24) (4 micrograms/rat) were dose-dependently antagonized by the intraperitoneal injection of the selective Ca++ channel inhibitor, nicardipine (dose range: 0.1-1 mg/kg). These data suggest that the influx of Ca++ into target neurons is a step of key importance for the occurrence of ACTH-induced behavioral signs, and that Ca++ may play the role of second intracellular messenger for the behavioral effects of melanocortins. PMID- 8463552 TI - Hormonal regulation of glucose transporters in muscle cells in culture. PMID- 8463554 TI - Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes. AB - The effect of retinoic acid (RA) on thyroid peroxidase (TPO) and thyroglobulin (Tg) gene expression was investigated in cultured human thyrocytes. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH 5mU/ml and RA 0, 0.01, 0.1, 1.0 microM for 72 h respectively. The samples were then subjected to Northern gel analysis. Northern gel analysis using the specific cDNA probes showed that RA suppressed the accumulation of TPO and Tg mRNA stimulated by TSH in a time- and dose-responsive manner. Furthermore, RA inhibited forskolin and 8 Bromo-cyclic-AMP-induced TPO and Tg gene expression, suggesting a distal action site for these cAMP mediated gene expressions. Immunoprecipitation analysis using the specific monoclonal antibodies showed that TSH increased newly synthesized 100, 75, 36-kDa [35S] TPO. The increased de novo TPO was markedly inhibited by RA. Tg secretion from monolayer cultures was measured by radioimmunoassay. RA also inhibited TSH-induced Tg secretion in a dose dependent manner. RA did not affect [3H] thymidine uptake into primary cultured human thyrocytes. In conclusion, RA inhibits the synthesis of TPO and Tg via the suppression of thyroid-specific gene expression although the exact site of RA action on these genes in human thyroids remains to be further elucidated. These results suggest that RA may play a regulatory role in Tg and TPO gene expression, subsequently resulting in the suppression of thyroid hormone synthesis. PMID- 8463555 TI - Epidermal growth factor receptor and lipid membrane components in human lung cancers. AB - The binding of 125I-epidermal growth factor (EGF) to the plasma membranes of 54 samples of human lung tumors was determined. These included 34 squamous cell carcinomas and 20 adenocarcinomas. Twenty samples of histologically normal lung excised surgically along with the tumors were used as controls. Most of the plasma membranes showed an EGF receptor level higher than that of normal tissue. A moderate increase in the amount of 125I-EGF bound (2-5 fold) was observed in the majority of the tumors. Only a few cases (5-10% of the total) showed a large increase (> than 10 fold). The binding of 125I-EGF was compared with clinical stages and grades of differentiation. No correlation between the stage of the tumor and 125I-EGF binding was observed. However, the highest levels of EGF receptor (EGF-R) were found in poorly differentiated squamous cell carcinomas. The total amount and the distribution pattern of gangliosides and phospholipids were analyzed in individual tumors. A decrease in GD1b, GD1a and sphingomyelin and an increase in GM1 and GM3 was observed. No correlation was detected when tumors with the highest or lowest levels of gangliosides or phospholipids were compared with tumors exhibiting the highest binding of 125I-EGF. PMID- 8463557 TI - [Medical termination of pregnancy. Who decides? Who terminates? Who regulates? Questions for the legislator to work on]. PMID- 8463556 TI - [Anxiety and depressive disorders in the postpartum period in pregnant females]. AB - Several authors have found that caesarean section might be a risk factor for post partum depression, while others consider that mood disturbances are not a specific response to delivery and can be observed in women undergoing hysterectomy. This longitudinal prospective study was carried out in 156 in patient women at the Maternity department of Louis Mourier hospital, near Paris. These women were divided into three groups: 52 with normal delivery, 63 with caesarean section and 41 with gynecological surgery. Seventeen per cent of the women who had delivered suffered from baby-blues. The figure for anxiety (De Bonis scale > or = 20) was 23% in the 1st group, 41% in the 2nd group and 54% in the 3rd group. The figure for mood disturbances (according to DSM III criteria) was 4% in the 1st group, 16% in the 2nd group and 21% in the 3rd group. There was no significant difference between the 3 groups in figures for anxiety and depression during the first 3 months after delivery or surgery, but anxiety and depression ratings seem to fall faster and more steadily in women who had surgery. PMID- 8463558 TI - [Complications of laparoscopic surgery...(continued)!]. PMID- 8463559 TI - [The C.C.L. culdotomy extractor for laparoscopic surgery]. PMID- 8463560 TI - [Demons-Meigs syndrome]. PMID- 8463561 TI - [Laparoscopic treatment of extra-uterine pregnancy. Results apropos of a series of 109 cases]. AB - We report our experience concerning the laparoscopic treatment of ectopic pregnancy (EP). One-hundred and nine women with EP were treated in our department over a 4 year period, between February 1988 (date of our first laparoscopic surgery for EP) and December 1991. Twenty-two of these women underwent laparotomy and the remaining 87 laparoscopic surgery alone. Four therapeutic failures were noted in women treated by laparoscopy. Our results are compared with those of other series and the indications, as well as the modalities of laparoscopic treatment are detailed. It is concluded that laparoscopic surgery of EP is a reliable method which must always be considered, except for a few rare indications. PMID- 8463562 TI - [Pregnancy following female surgical sterilization. A study apropos of 38 cases]. AB - A study of 38 cases of pregnancy that occurred after sterilisation between 1st January 1981 and the 30th September 1987 at the Maternity and Neonatology Department of La Rabta, Tunis. This complication is rare because the overall global figure for failure is 7.1/1000. This is what is found in the literature. When we came to analyse the failures we found there were two groups: 15% of these failures were in women who had been sterilised correctly. This also happens when women have been sterilised with the Yonn ring as with Pomery's ligation technique. In this case when patients become pregnant there is a big chance of their being ectopic (2 tubal pregnancies as against 5 intrauterine pregnancies). 85% of failures were due to technical faults. They particularly happen with laparoscopic sterilisation (85%). They are usually due to lack of experience on the part of the operator. In any case patients do not like it; in fact 73.7% of the patients asked for a termination of the pregnancy and sterilisation was repeated in 87% of the cases. PMID- 8463563 TI - [Treatment using laparoscopic surgery of dermoid cysts. Apropos of a series of 33 cysts]. AB - Laparoscopy is a surgical method which is now widely used for the treatment of ovarian cysts. The authors wish to present their experience concerning the management and treatment of dermoid cysts or dysembryomas since these lesions embody all the problems persisting in this field. They report 33 cases exclusively treated by laparoscopic surgery in a series of 407 adnexal cysts treated over a 4-year period (April 1988 to April 1992). As regards diagnosis, the principal difficulty is not to miss the odd malignant lesion (1 to 2%) encountered mainly in older women. Technically, the most delicate stage in the operation is extraction of the cyst, especially when it is large and has an important solid component. Provided all precautions are taken in the diagnosis and the operative technique, this new method seems to be quite acceptable as it enables women who carry these lesions, which require excision, to benefit from the well-known advantages of laparoscopic surgery. PMID- 8463564 TI - [The malignant potential of adenofibroma and cystadenofibroma of the ovary and mesovarium. 118 cases including 13 proliferative and 5 carcinomatous]. AB - The relationship between adenofibroma and cystadenofibroma and the frequency and features of carcinomas developed on these benign tumours are little known. Eight hundred and forty-five epithelial tumours of the ovary diagnosed over a 10-year period have been re-examined. One-hundred and eighteen adenofibromas and cystadenofibromas were recorded. One-hundred were benign and formed an architectural spectrum from which emerged: (1) surface papillary adenofibroma accounting for 5% of the cases and appearing at a mean age of 27 years; (2) cystadenofibroma in 77.5% of the cases at a mean age of 53 years; (3) adenofibroma in 17.5% of the cases at a mean age of 64 years. Adenofibroma was bilateral in 18 cases. Among the other cases were an endometrioid cyst and two simple serous cysts. The cells were serous in 110 cases, mucinous in 6 cases and weakly acidophilic to clear in 2 cases. Eighteen of these tumours were malignant: 13 were associated with epithelial hyperplasia and 5 with a carcinoma. The 13 adenofibromas with atypical epithelial hyperplasia (at a mean age of 60 years) were all made of serous cells; 6 of them were low-grade and 7 high-grade tumours with 3 microinvasions. One patient died at the age of 78, of an unknown cause; the others are still alive after a mean follow-up of 11.3 years. The 5 invasive carcinomas appeared on an adenofibroma at the mean age of 70 years; 3 patients died (2 of metastases), one is alive after 9 years and one was loss sight of.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463565 TI - [A rare ovarian pseudotumor: massive edema of the ovary]. AB - The authors report a case of massive ovarian edema which declared itself by pain in the abdomen and pelvis and an ovarian mass measuring 13 cm in diameter, occurring in a 22-year-old woman. Since it was not possible to make a diagnosis by any frozen-section examination, histology was carried out on the ovary that had been removed. This showed that the stroma of the ovary had become separated by massive edema preserving the albuginea and the superficial cortex. This case history of massive edema of the ovary shows the characteristics of this ovarian pseudotumour as described in the literature. The principal differential diagnoses of the condition are oedematous fibroma, and myxoma of the ovary. Apart from the fact that torsion of the adnexae can occur in some of these cases, the pathogenesis is still unexplained. When an ovarian tumour is found in a young woman a frozen-section examination must be carried out to make the diagnosis and perhaps avoid oophorectomy, particularly when untwisting a torsion can lead to resorption of the edema. PMID- 8463566 TI - [Teratogenicity of retinoids. A case and review of the literature]. AB - Retinoids are vitamin A derivatives used in dermatology. One of them, isotretinoin, is frequently prescribed for refractory juvenile acne. The teratogenetic power of this drug is substantial, being estimated at 15 to 45% of exposures in utero. The risk is maximum in the first trimester of pregnancy and persists up to one month after treatment has been discontinued. The most frequently described multiple malformation syndrome involves the face, the central nervous system and the heart. There is also a 20 to 30% rate of spontaneous abortion. The authors report a case where exposure during the first trimester did not result in foetal malformation. From a full review of the literature the various malformations observed, the presumed mechanisms of teratogenesis and the strict rules of prescription and surveillance in women child-bearing age are presented. The problem of the measures to be taken in case of retinoid treatment during pregnancy is discussed. The teratogenic risk from other retinoids is dealt with. PMID- 8463567 TI - [Embryofetopathy of the newborn infant of a phenylketonuric mother. A diagnosis not to be missed]. AB - Children with phenylketonuria (PKU) detected in the neonatal period and who have received the appropriate diet develop normally whatever their sex. However, female PKU patients who, before becoming pregnant, do not take the precaution to follow a diet bringing phenylalanine to "normal levels" (2 to 5 mg in 100 ml of blood) give birth to children presenting with severe embryofoetal damage (e.g. intrauterine growth retardation, microcephaly, mental retardation, various malformations) directly due to their hyperphenylalaninaemia (20 mg or more in 100 ml of blood under a free diet). It is important to know these facts, since the benefits of systematic neonatal PKU detection may be cancelled by this late complication. The therapeutic approach in such cases is a follows: 1. Young women with known PKU must be informed of this risk and how it can be avoided by a preconception therapeutic diet. This means that they must permanently reside in the same geographical area, receive an adequate information at the end of puberty, use and effective contraception method and program their pregnancies preceded by a return to low phenylalanine diet. 2. Doctors must remember that because PKU detection has not become systematic until 1978, PKU girls of child bearing are remain undetected, that they are not always mentally debilitated and can normally five birth to children with embryofoetal damage. In case of e.g. unexplained intrauterine growth retardation or microcephaly, it is necessary to perform a Guthrie test on the woman, since a prenatal diagnosis may lead to therapeutic abortion, and a postnatal diagnosis to a genetic counselling which will avoid recurrences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463568 TI - [Prenatal diagnosis of adenomatoid malformation of the lung. 5 cases and review of the literature]. AB - The authors report five cases of adenomatoid malformation of the lung (AML) diagnosed in the antenatal period. Since 1977, when Stocker et al. published their classification of these malformations into three anatomical types, the ultrasonographic features have been well systematized, thereby enabling treatment to be modified according to the AML type. Type I and II have a good prognosis (about 20% of neonatal deaths) and only require close supervision. Thoracocentesis may be necessary in case of significant anasarca or hydramnios. The progression and prognosis of type III AML are very bad, since a favorable course is observed in only 10% of the foetuses. Intrauterine surgery has already been successfully attempted in on case and might modify the situation. Most authors are in favour of therapeutic abortion when signs of bad prognosis are present. PMID- 8463569 TI - [Acute aortic dissection during pregnancy. Surgical treatment with maternal and fetal rescue]. AB - Acute aortic dissection (AD) seldom affects young women, but when it occurs it is, in almost one out of two cases, during pregnancy. We report a case of severe AD during pregnancy in which emergency surgery immediately saved the life of the mother and the foetus. The mother died of cardiac complications 13 days after the operation; the condition of the newborn is satisfactory. PMID- 8463570 TI - [Pregnancy and non-Hodgkin's lymphoma: a case]. AB - We report for the first time in the French literature the case of a malignant non Hodgkin's type lymphoma associated with pregnancy in a 19 year old woman. The evolution with corticotherapy was rapidly unfavourable and led to premature birth of a child who died 24 hours later, and to maternal death 48 hours later in spite of an attempt of chemotherapy. The prognosis of these tumours is bad, for the fetus because of the risks of premature delivery, for the woman because of the risks of tumoural evolution during the postpartum period. PMID- 8463571 TI - [Cerebral tumors and pregnancy. Apropos of 8 cases]. AB - Pregnancy is an aggravating factor for brain tumours on which it acts by three mechanism: acceleration of tumour growth, increase of peritumoral oedema and the immunotolerance to foreign tissue antigens that is proper to pregnancy. Histologically, the brain tumour most frequently encountered is glioma, usually revealed during the third trimester. Brain tumours is pregnant women have no special clinical features, and their diagnosis rests on computerized tomography or nuclear magnetic resonance completed, if required, by stereotactic biopsy. Following a review of the literature, the authors present an updated description of the neurological and obstetrical actions to be taken, illustrated by a report of eight personal cases. The indications for surgery depend on the site and histological nature of the tumour. As regards obstetrical measures, induced therapeutic abortion and caesarean section, no longer routinely performed, are now being replaced by vaginal delivery with systematic instrumental extraction. In both mother and foetus the prognosis has improved over the last ten year, but it remains very sombre. PMID- 8463572 TI - [Advanced cancer of the rectum and pregnancy. Review of the literature apropos of a case]. AB - The authors report a case of advanced rectal cancer in a pregnant woman of 30 years of age. It was a glandular adenocarcinoma discovered in the second trimester of pregnancy. The clinical picture was one of rectal bleeding with digestive disturbances. The patient had a caesarean operation at 29 weeks of amenorrhoea because of a change in her general state. Post-operatively palliative chemotherapy was started. The patient died on the 13th day. PMID- 8463573 TI - [Placental aspergillosis: myth or reality? Apropos of a case with fetal death in utero]. AB - The authors report an original case-history of massive aspergillosis of the placenta that occurred in a 24 year old primigravida who had had no previous history or clinical changes in pregnancy. It caused fetal death in utero with retention and maceration of the fetus. Macroscopic examination showed that the left lip was cleft and that the placenta was studded with isolated confluent diffuse whitish granulations. Histologic examination made us think that these appearances were those of aspergillar granulomas occurring even in the placental villi and intravillous spaces. Laboratory findings showed that there was Aspergillus Niger in the blood of the mother. A wide search of the literature failed to find any case in humans. On the other hand aspergillosis occurs frequently in animals causing intrauterine growth retardation and prematurity with abortion. There is great economic loss as a result. Why the animal placenta should be susceptible to infection of aspergillosis and how it acquires it is discussed! Finally the association of aspergillosis of the placenta with a cleft lip found in our case, is unique and one wonders if there is any relationship. PMID- 8463574 TI - [Distal tubal surgery using laparoscopy]. AB - Between January 1987 and May 1990, forty-four women were treated in our department by laparoscopic surgery for distal tubal pathology. Among them, 10 had an intrauterine pregnancy (22.7%) and 2 had an ectopic pregnancy (4.5%) within 28 months after surgery. Subsequently, our results were expressed in terms of the type of operation performed (fimbrioplasty or neosalpingostomy) and according to the tubal and adhesion scores (Mage and Bruhat). We found that most pregnancies were obtained within the first 16 months, that fimbrioplasty gave better results than neosalpingostomy (35.7% versus 16.6%) and that the tubal score was fairly predictive and more so than the adhesion score. These results enabled us to keep as indication of distal tubal laparoscopic surgery those patients who had pure distal tubal lesions with a tubal core of 1 to 2 and normal other parameters of infertility. In case of failure, i.e. if the woman does not become pregnant within 12 months post-laparoscopic surgery, in vitro fertilization is advised. PMID- 8463575 TI - [The value of RU-486 (mifepristone) in medical indications of the induction of labor at term. Results of a double-blind randomized prospective study (RU-486 versus placebo)]. AB - One hundred and twenty term women (> 37.5 weeks amenorrhea) with unripe cervixes (Bishop < 4) and with a clear clinical indication for labour induction were randomized to receive either mifepristone (RU 486) or placebo. The patients' regimens consisted of 200 mg of mifepristone on days 1 and 2 over an observation period of 4 days, with labour induction planned for day 4. Within 12 hours after taking the first tablet, fetal distress was diagnosed in 8 patients (3 in the Mifepristone group and 5 in the control group), who underwent immediate cesarean section. These 8 patients could not therefore participate in our survey and have been excluded from the final results. Forty one patients had spontaneous onset of labour, 31 in the mifepristone group and 10 in the control group (p < 0.001). Forty seven patients needed cervical maturation with prostaglandin, 32 from the control group and 13 from the mifepristone group (p < 0.001). Thirteen patients in each group had cervical maturation sufficient for classical labour induction. We noted that patients delivering vaginally needed significantly lower amount of oxytocin in the mefepristone group and that the mean time interval between day 1 and the onset of labour was also significantly shorter in this group. The high cesarean section rate (32%), which is equivalent in both the placebo and the treated groups, may be attributed to the fact most of the patients in this survey had high risk pregnancies. There was no difference in the occurrence of fetal distress during labour in the 2 groups. Neonatal parameters were similar in both groups. These results establish mifepristone as an induction agent for the initiation of labour in term women. Though more studies are needed, Mifepristone has shown itself to be safe and appropriate in situations where labor has to be induced in term women. PMID- 8463576 TI - The hand and evolution. PMID- 8463577 TI - Tension band arthrodesis of small joints in the hand. AB - Two-hundred three patients underwent 290 tension band arthrodeses of the metacarpophalangeal and proximal interphalangeal joints of the hand. Nine patients (3%) failed to achieve bony union, four had painless pseudarthroses, and one patient had a small finger amputation. Twenty-five fusions (9%) required hardware removal. There were 10 superficial infections (all responded to oral antibiotic therapy), and three fusions were malrotated. Tension band arthrodesis is our choice for fusion of the metacarpophalangeal and proximal interphalangeal joints. It is reliable and provides stable fixation, pins do not protrude, and external splinting is unnecessary in the cooperative patient. PMID- 8463578 TI - Stability and constraint of the proximal interphalangeal joint. AB - The kinematics of the intact proximal interphalangeal joint of 12 fresh cadaver index fingers were measured by means of an electromagnetic tracking system. The specimens were then randomly divided into two groups for ligament sectioning in two different sequences and for testing under lateral stress. Lateral stress of the intact proximal interphalangeal joints produced an average of 5 degrees of adduction and 9 degrees of supination motion throughout the arc of flexion/extension. Maximum lateral angulation was 15 degrees under 1 kg of force (30 N cm) applied at the distal end of the middle phalanx. Joint angulation increased to 20 degrees after total sectioning of the collateral ligament. Joint laxity was greatly reduced in full extension, in full flexion, and when the muscles were loaded. The proximal interphalangeal joint remained stable when one half of the collateral ligament was left intact. The results indicate that lateral stability of the proximal interphalangeal joint is provided primarily by the collateral ligament. When the lateral stress test is normal in proximal interphalangeal joint extension, an additional test in 20 to 30 degrees of flexion should be considered to avoid a false-negative result. Angulation greater than 20 degrees is abnormal and indicates a loss of collateral ligament integrity. PMID- 8463579 TI - Camitz palmaris longus abductorplasty for severe thenar atrophy secondary to carpal tunnel syndrome. AB - This is a retrospective review of 29 patients (33 hands) who underwent a palmaris longus transfer because of severe thenar atrophy secondary to median nerve entrapment at the wrist. The mean follow-up was 17 months. Ninety-four percent of our patients were satisfied because their thumb function improved. Twenty-six of the patients had the transfer at the time of initial release of the carpal tunnel, and three patients had the transfer when the carpal tunnel was released a second time. The transfer helps with thumb palmar abduction, and the palmaris longus is an expendable muscle for transfer. PMID- 8463580 TI - Upper extremity tourniquet tolerance. AB - Twenty unsedated volunteers were tested to compare the relative tolerance of an arm tourniquet on one side and of a forearm tourniquet on the other. The forearm tourniquet was tolerated an average of 13 minutes (45%) longer and was consistently rated as less painful during and immediately after the test. No subject tolerated the arm tourniquet longer than the forearm tourniquet. Two peaks of discomfort were found, one just before deflation beneath the tourniquet and one in the hand 2 minutes later. Ulnar nerve distribution paresthesias were the earliest changes experienced; however, complete numbness occurred first in the median nerve distribution. Complete paralysis occurred 7 minutes later (24%) with the forearm tourniquet. Pulse rate did not correlate with tourniquet pain, but blood pressure did. No measurable tourniquet-induced edema occurred on either side. PMID- 8463581 TI - The effect of hypothermia on changes in isometric contractile function in skeletal muscle after tourniquet ischemia. AB - The effect of hypothermia on changes in contractile function of skeletal muscle observed after an episode of tourniquet ischemia has been investigated. Male Wistar rats were subjected to 2 hours of unilateral hypothermic (n = 33) or normothermic (n = 39) pneumatic tourniquet ischemia of a hind limb. Isometric contractile function was measured bilaterally from the gastrocnemius muscles after 1, 7, 14, 28, or 42 days of recovery. Compared to muscle subjected to normothermic ischemia, muscle that underwent hypothermic ischemia demonstrated more twitch tension at 1 day postischemia, higher maximum tetanic tension at all time periods, including 6 weeks after ischemia, and greater muscle weight at 6 weeks. Rat gastrocnemius muscle function is much better 1 day to 6 weeks after 2 hours of hypothermic ischemia than after 2 hours of normothermic ischemia. The results thus document the benefit of hypothermia during tourniquet ischemia in preventing or minimizing the changes in isometric contractile function observed after normothermic ischemia. PMID- 8463582 TI - The use of ultrasonography to detect a radiolucent foreign body in the hand: a case report. PMID- 8463583 TI - Elbow arthroscopy in a mostly athletic population. AB - The effectiveness of elbow arthroscopy was assessed in 35 consecutive patients (primarily weight lifters and baseball players) treated by one surgeon. The most commonly treated lesions were loose bodies and impinging spurs. Most elbow problems resulted from repetitive or acute athletic trauma. Repetitive stress injuries usually involved the athlete's dominant arm (91%). A standardized rating system demonstrated significant improvement at 24 months' average follow-up. Flexion and extension improved an average of 9 and 6 degrees, respectively. Elbow arthroscopy appears to be a safe and effective treatment for athletes, allowing most a full return to participation in sports. PMID- 8463584 TI - Elbow pain presaging myocardial infarction: a case report. PMID- 8463585 TI - Anatomy of trapeziometacarpal ligaments. AB - The stabilizing ligaments of the thumb trapeziometacarpal joint were identified and studied during anatomic dissections of 30 hand specimens. Five main ligamentous structures were identified: (1) the anterior oblique ligament, (2) the ulnar collateral ligament, (3) the first intermetacarpal ligament, (4) the posterior oblique ligament, and (5) the dorsoradial ligament. It was observed that the anterior oblique ligament is the primary stabilizer of the trapeziometacarpal joint and is taut in abduction, extension, and pronation. The first intermetacarpal, ulnar collateral, and posterior oblique ligaments appear to be secondary stabilizers. In every specimen, the first intermetacarpal, ulnar collateral, and posterior oblique ligaments merged to form a force nucleus at the base of the first metacarpal. The dorsoradial ligament did not play a primary or secondary role in thumb stability. The clinical correlation of this anatomic study suggests that, at the minimum, the reconstruction of a primary thumb trapeziometacarpal ligament (anterior oblique ligament) is essential in the treatment of degenerative arthritis to maintain thumb stability. PMID- 8463586 TI - Acute and late radial collateral ligament injuries of the thumb metacarpophalangeal joint. AB - Eighteen patients were treated surgically for injuries to the radial collateral ligament of the thumb metacarpophalangeal joint. Late repairs were performed in 12 and immediate repairs in 6. At follow-up after a mean of 6 years, 94% of the patients were completely satisfied with the results. No patients had significant pain in their thumbs, and none were limited in work or avocational activities. A stable repair was maintained in all patients. There was no difference in grip or pinch strengths between the immediate and late groups. Loss of thumb motion in the late group (mean = 77% of normal) was slightly more than that in the immediate group (mean = 89% of normal). Late repair gives equally good subjective results and causes a slightly greater loss of thumb motion than immediate repair. PMID- 8463587 TI - Contact patterns in the trapeziometacarpal joint: the role of the palmar beak ligament. AB - Twenty-three cadaver forearm specimens were mounted on a Plexiglas acrylic plastic base for study of the trapeziometacarpal joint. Extrinsic and intrinsic motors were loaded to simulate lateral pinch, and pressure-sensitive film was used to record joint contact patterns in various functional positions. The palmar compartment of the trapeziometacarpal joint was the primary contact area during flexion adduction of the thumb ray in lateral pinch. Simulation of dynamic pinch and release produced dorsal enlargement of the contact pattern, suggesting physiologic translation of the metacarpal on the trapezium. Detachment of the palmar beak ligament resulted in dorsal translation of the contact area, producing a pattern similar to that of cartilage degeneration seen in the osteoarthritic joint. End-stage osteoarthritic specimens had a nonfunctional beak ligament and demonstrated a pathologic total contact pattern of joint congruity that was unaffected by further manipulations of the beak ligament. This work defines the contact patterns in the normal and diseased trapeziometacarpal joint and establishes the important influence of the palmar beak ligament on those contact areas. PMID- 8463588 TI - An evaluation of rapid exchange and simultaneous grip tests. AB - The usefulness of the rapid exchange grip test and a modification of this test, the rapid simultaneous grip test, in detecting submaximal grip efforts was evaluated. Uninjured subjects giving maximal or submaximal grip efforts were tested at grip rates of 80 and 100 repetitions per minute. Rapid exchange grip at 80 repetitions per minute yielded a sensitivity of 86% and a specificity of 97%. Rapid simultaneous grip at 80 repetitions per minute yielded a sensitivity of 81% and a specificity of 93%. Poorer sensitivities and specificities resulted when a clinical population of patients was tested. Patients who were not giving maximal efforts tended not to comply with the test protocol. The rapid exchange and rapid simultaneous grip tests do assist in detecting submaximal grip efforts; limits to these tests are emphasized. PMID- 8463589 TI - Measurement of wrist, metacarpophalangeal joint, and thumb extension strength in a normal population. AB - An objective method of measuring isometric wrist, finger (metacarpophalangeal joints) and thumb extension strength was developed, and values for a normal population were defined. Disability due to extensor dysfunction was not assessed in this study. The testing technique involved the use of a load cell myometer held in a specially constructed jig. A total of 2232 measurements in 372 persons were made. Mean values for the strength of extension were as follows: men--wrist, 13 kg; metacarpophalangeal joint, 6 kg; thumb, 3 kg; women--wrist, 7 kg; metacarpophalangeal joint, 4 kg; thumb, 2 kg. Strength was greatest in the third decade and decreased in each subsequent age group. Wrist extension strength was 10% greater in the dominant hand. Interrater and test-retest reliability were assessed and found to be satisfactory. The method is proposed primarily as a clinical research tool, providing the clinician with an objective means of assessing wrist, metacarpophalangeal joint, and thumb extensor function. Potential applications include measurements of recovery after radial nerve injury or grafting and after other reconstructive procedures to restore extensor function. PMID- 8463590 TI - Multiple hemophilic bone cysts in the hand. PMID- 8463591 TI - Mastocytosis of bone in the hand without systemic disease. PMID- 8463592 TI - Low-velocity gunshot wounds of the metacarpal: treatment by early stable fixation and bone grafting. AB - The results of early stable fixation of 64 metacarpal fractures due to low velocity gunshot wounds in 49 patients were reviewed retrospectively. These reconstructive procedures were performed between 1 and 7 days after injury and involved stable internal fixation supplemented with primary iliac crest bone graft in 40 fractures with bone loss or comminution. Postoperatively, the hands were splinted with 90 degrees of metacorpophalangeal flexion while early interphalangeal motion was emphasized. Follow-up averaged 12 months, with a range of 4 months to 7 years. Primary bone union was achieved in all metacarpals. The average range of motion was 65 degrees for the metacarpophalangeal joint, 72 degrees for the proximal interphalangeal joint, and 60 degrees for the distal interphalangeal joint. Complications included two superficial infections. There were no cases of deep infections or persistent draining wounds. Early, stable fracture fixation of these injuries achieved union, alignment, and early rehabilitation with no appreciable increase in morbidity. PMID- 8463593 TI - Index transposition after resection of the long finger ray. AB - Ten patients underwent index-to-long-finger ray transposition for repair after resection of the long finger ray. Care was taken to preserve the second web space and prevent painful neuromas. Rigid internal fixation was achieved with a T plate, and mobilization was started immediately. There were no nonunions. Postoperative motion was equal to preoperative motion in acute cases and equal or better in chronic cases. Mean grip strength was 0.65, and pinch strength was 0.78 compared with the uninjured hand. There were no painful neuromas, hypersensitive scars, or deterioration of monofilament or two-point sensibility. The breadth and appearance of the first and second web spaces were equal bilaterally. Digit alignment and rotation were normal. The six patients receiving worker's compensation returned to work in between 3 and 24 weeks, and the other patients returned in between 11 days and 12 weeks. PMID- 8463594 TI - Sensibility deficiencies in the hands of children with spastic hemiplegia. AB - We evaluated 40 children with spastic hemiplegia due to cerebral palsy for sensory function and relative limb size in the affected and unaffected upper extremities. Sensory function of each limb was evaluated with respect to stereognosis (12 objects), two-point discrimination, and proprioception. Four size measurements of each limb were made: arm and forearm circumference and forearm and forearm-hand length. This study showed that 97% of the spastic limbs had a stereognosis deficit, 90% had a two-point discrimination deficit, and 46% had a proprioception deficit. Thus sensory deficits are the rule rather than the exception in children with spastic hemiplegia. Those children with severe stereognosis deficits had significantly smaller limbs in all four measurement parameters than the children with mild or moderate stereognosis deficits. In the preoperative evaluation of children with spastic hemiplegia, severe size discrepancy is a physical examination tool that can be used as a predictor of severe sensory deficits. This information is helpful for the hand surgeon in establishing realistic surgical goals. PMID- 8463595 TI - Brachial plexus injury after median sternotomy. AB - Serious brachial plexus injury after median sternotomy is uncommon. However, affected patients experience considerable morbidity and their return to regular employment is often delayed. The pathogenesis of the injury is multifactorial. Wide sternal retraction is the major etiologic factor. Management is primarily conservative and should be guided by a team experienced in upper limb and hand surgery. Our experience at a major referral center during a 3-year period is described. PMID- 8463596 TI - Functional restoration of elbow flexion in brachial plexus injuries: results in 167 patients (excluding obstetric brachial plexus injury). AB - From 1985 to 1990, 167 patients were treated for impaired elbow flexion caused by brachial plexus injury. Surgical procedures were divided into two categories: nerve reconstruction (128 patients) and muscle or tendon transfers (39 patients). Surgery in the nerve reconstruction group included direct suturing, nerve grafting of portions of the brachial plexus responsible for elbow flexion, or nerve transfer (intercostal, phrenic, or spinal accessory nerve) to the musculocutaneous nerve. The second category included tendon or muscle transfer or a functioning free muscle transplantation for biceps replacement. Results were assessed by the Medical Research Council grading system and weight-lifting evaluation. Functional results revealed that nerve reconstruction was superior to muscle tendon transfers, direct suturing was superior to nerve grafting, short nerve grafts (< 10 cm) were superior to long nerve grafts (> 10 cm), infraclavicular plexus injuries did better than supraclavicular injuries, vascularized ulnar nerve grafts (if indicated) were superior to conventional long nerve grafts, ruptured plexus injuries recovered better than root avulsions. Intercostal nerve transfer to the musculocutaneous nerve has satisfactory results. In the muscle tendon transfer group, Steindler flexorplasty resulted in upgrading muscle strength from level one to level two. Functioning free muscle transplantation had results similar to the latissimus dorsi transfer. PMID- 8463597 TI - Evaluation of patients with thoracic outlet syndrome. AB - This prospective study evaluated 50 patients with thoracic outlet syndrome. Detailed history and pain scale evaluation preceded physical examination, which included provocative tests (positional and compressive) and sensory evaluation (baseline and postprovocative vibration thresholds and two-point discrimination). Only one patient had a positive nerve conduction study/electromyograph at the brachial plexus level. Thirty-two percent of the patients had a compressive anatomic abnormality as seen on a computed tomography scan. Ninety-four percent had positive provocative position and compression test results. Two-point discrimination was normal in 98%. Clinical assessment of thoracic outlet syndrome is best achieved by reproduction of symptoms with compression and positional provocative testing. Results of the majority of tests (nerve conduction studies/electromyographs, x-ray films, sensory tests) will be normal. Measurements of changes in sensory thresholds during provocation of symptoms may be useful. PMID- 8463598 TI - Ulnar translation of the carpus in rheumatoid arthritis: an analysis of five determination methods. AB - Five x-ray methods of assessing ulnar translation of the carpus were compared to each other. Overall, we found the uncompensated semiquantitative method proposed by Gilula et al. to be the most practical and the best method with a sensitivity index of 82%, a specificity index of 88%, an accuracy of 87%, and an interobserver correlation of 90%. The method, however, decreased in specificity and accuracy when a corrective formula was applied to adjust the ulnometacarpal angle to zero degrees deviation. Our conclusion is that the sensitivity indices are relatively low for all methods, and underdiagnosis may occur. At present the semiquantitated method of Gilula et al. is the most practical, with the highest sensitivity index, and is recommended as a screening tool for assessment of ulnar translation of the carpus. PMID- 8463599 TI - Palmar midcarpal instability: results of surgical reconstruction. AB - We reviewed the cases of 13 patients who underwent 15 surgical procedures for palmar midcarpal instability from 1981 to 1989. Six patients had a limited midcarpal arthrodesis, and nine patients had one of four different soft tissue reconstructive procedures. One hundred percent clinical follow-up was obtained at an average of 48 months. All six of the limited midcarpal arthrodeses were successful. Six of the nine soft tissue reconstructions failed. However, one procedure, a distal advancement of the ulnar arm of the arcuate ligament combined with a dorsal capsulodesis, restored stability in three of five wrists. We concluded that patients with palmar midcarpal instability may have significant disability that may be refractory to nonsurgical management. Limited midcarpal arthrodesis provides definitive treatment. PMID- 8463600 TI - Preliminary experience with Ilizarov method in late reconstruction of radial hemimelia. AB - We report the outcome of ulnar lengthening with the Ilizarov technique in five adults with radial hemimelia and previous wrist centralization. The indications for ulnar lengthening in these patients were either a functional deficit due to the short ulna or poor appearance that caused the patient significant unhappiness. All patients had a successful lengthening of the ulna, with a gain in length from 4 to 13 cm; however, the procedures were prolonged (7 to 25 months), and all patients experienced complications. At the time of follow-up examination no patient had residual pain or paresthesias. In four of five patients, although ulnar lengthening resulted in somewhat stiffer digits, it improved function of the extremity as a whole. When asked if they would repeat the lengthening, knowing what they know now, all five replied that they would. The technical difficulties encountered in these cases suggest a cautious approach to ulnar lengthening. This is a long, arduous, painful process that requires a psychologically robust patient. If the ulna is very short preoperatively, lengthening can enhance the volume of space accessible to the hand and in that way improve function. PMID- 8463601 TI - Posttraumatic physeal bar formation in the digit of a child: a case report. PMID- 8463602 TI - Biomechanical evaluation of distal radioulnar reconstructions. AB - Numerous reconstructive procedures have been described for the treatment of chronic instability of the distal radioulnar joint or instability of the stump of the resected distal ulna. This biomechanical study presents an evaluation of the three basic design types that have been used in reconstruction. The initial static stability provided by the reconstructions was tested and compared with the stability of the intact joint. Our findings show that all reconstructive procedures failed to restore natural joint stability. A radioulnar sling design was the most effective of the three types, whereas tenodesis procedures and ulnar collateral ligament reconstruction were much less effective in providing stability. We conclude that current designs have significant biomechanical shortcomings. On the basis of our observations during testing, we believe that improved designs will require an intra-articular reconstruction that more closely duplicates the biomechanical functions of the triangular fibrocartilage complex. PMID- 8463603 TI - Partial excision of the triangular fibrocartilage complex articular disk: a biomechanical study. AB - A cadaver study was performed to evaluate the effects of partial and complete excisions of the articular disk of the triangular fibrocartilage complex on the kinematics of the distal radioulnar joint and the structural integrity of the triangular fibrocartilage. An excision that did not violate the peripheral 2 mm of the disk and that comprised less than two thirds of the disk area resulted in no significant kinematic or structural changes, but larger excisions produced measurable changes. These results provide further support for limited excision of central triangular fibrocartilage complex tears. PMID- 8463604 TI - Measurement of carpal bone geometry by computer analysis of three-dimensional CT images. AB - The aim of this project was noninvasively to analyze and quantitate the geometry, load transfer characteristics, and spatial relationships of the carpal bones by using a new three-dimensional CT scan reconstruction technique. The determination of mechanical parameters such as distances between centroids and between bone surfaces, carpal alignment, volumes, surface areas, and contact areas can provide the basis for comparison between normal wrists and wrists with a variety of progressive instability patterns, types of fracture, pathologic and posttraumatic states, and different simulated surgical procedures. This new technology has demonstrated a volumetric accuracy of 94% and a linear accuracy of 97%. Simultaneous analysis of all articulating surfaces of multiple joints can be performed in cadavers and in patients because of the noninvasive nature of the imaging reconstruction technique. This new research offers much more information than has previously been available. It also promises direct application to the clinical setting and eliminates several limitations and questions that were inescapable with previous technology. PMID- 8463605 TI - Bilateral pronator syndrome associated with anomalous heads of the pronator teres muscle: a case report. PMID- 8463606 TI - The reverse flexor carpi ulnaris and ulnar nerve neuropathy. PMID- 8463607 TI - Intraosseous pressure in Kienbock's disease. AB - Intraosseous pressure was measured in the lunate of 10 patients undergoing surgery for Kienbock's disease. Using the styloid process of the radius and the capitate as reference points of bone pressure, I found a stasis rather than arterial insufficiency in the lunate. This pattern was observed regardless of the stage of the disease according to Stahl and regardless of the finding by technetium TC 99m-methylene diphosphonate scintigraphy. The significance of this finding is still unknown but questions the current concept that Kienbock's disease is caused by arterial insufficiency, because these results imply an interruption of the blood flow as a result of venous congestion. PMID- 8463608 TI - Dorsal approach to scaphoid nonunion. AB - The surgical approach for treatment of scaphoid nonunion usually involves various combinations of screws and Kirschner wires, with or without bone grafts. This article reports our results with 36 dorsal-approach bone grafting procedures for treatment of scaphoid nonunion with Kirschner wires. Union was achieved in 89%. The average follow-up was 5 years. Flexion/extension averaged 76% of the opposite wrist, and grip strength was 88% of the opposite hand. Ninety-one percent of the employed patients returned to their original jobs. The dorsal approach provides satisfactory exposure for fragment reduction and bone grafting. PMID- 8463609 TI - The scaphoid shift test. AB - The scaphoid test described by Watson has generally been accepted as the definitive test for scaphoid instability and uses pressure against the scaphoid tubercle as the wrist moves from ulnar to radial deviation for the evaluation. This article describes a stress test done with the wrist in neutral position, which actively provokes scaphoid instability. Variations in stability can be used to grade scaphoid laxity. PMID- 8463610 TI - The first nerve graft, Vulpian, and the nineteenth century neural regeneration controversy. AB - We present translations from the French of 1863 and 1870 papers in which Philipeaux and Vulpian reported performing first nerve allografts and then nerve autografts in dogs. With the latter, they had some evidence of success in two of seven animals. It is our belief, based on an extensive search of the literature, that this was the first nerve grafting performed. PMID- 8463611 TI - Benign gastric ulcer grossly resembling malignancy. A clinicopathologic study of 20 resected cases. AB - Twenty cases of benign gastric ulcers preoperatively interpreted to be malignant were reviewed clinicopathologically to clarify why these ulcers grossly appeared malignant. Macroscopically, the lesions often had an irregular margin (75%) and elevated surrounding mucosa (45%), and were often located on the greater curvature (40%) and near the pylorus (40%). Microscopically, most ulcers were large (21 mm) and shallow, reaching the submucosa (70%), and many were characterized by marked fibrosis (35%) and inflammatory cell infiltration (25%), sometimes accompanied by lymphoid hyperplasia. For such ulcers, which look malignant, careful examination by radiography, endoscopy, and biopsy should diminish the indications for surgery. PMID- 8463612 TI - Blastocystis hominis in inflammatory bowel disease. AB - We retrospectively examined the hospital course of 12 patients with exacerbated inflammatory bowel disease (IBD), who also had stool specimens positive for Blastocystis hominis to determine the effect of B. hominis on their disease. Bloody bowel movements were common with ulcerative colitis patients and watery diarrhea with Crohn's disease; other findings included abdominal pain, fever, nausea, and vomiting. All patients responded favorably to medical therapy. Three responded to treatment with corticosteroids alone, and one patient improved with bowel rest without medications. Five patients failed to improve on metronidazole; four of them responded to a subsequent course of corticosteroids, whereas the fifth patient became asymptomatic after erythromycin treatment for concomitant Campylobacter jejuni. Finally, three patients responded to treatment with metronidazole alone, which is known to eradicate B. hominis but may also have a beneficial effect on IBD. In no case did corticosteroid treatment worsen the condition. Our findings indicate that B. hominis is not a significant pathogen in IBD and treatment must be directed toward the underlying illness. PMID- 8463613 TI - Prospective study of abdominal ultrasonography before laparoscopic cholecystectomy. AB - To investigate the role of abdominal ultrasonography (US) in predicting possible difficulties during laparoscopic cholecystectomy, we performed preoperative US evaluation prospectively in 82 consecutive patients. We correlated our predictions of "easy" and "difficult" with difficulties experienced at operation in surgery. The binary outcomes were analyzed by taking both easy category of US and surgical operation as positive results and both difficult category as negative results. We obtained satisfactory sensitivity (93.8%), accuracy (81.4%), and positive predictive value (84.7%), but low specificity (35.3%) and negative predictive value (60%). The highly positive results were the result of careful US examination. The low specificity and negative predictive value were attributed to the fact that most surgically difficult cases were due to adhesions around the gallbladder, difficult indeed to detect at US. We conclude that thorough abdominal US examination before laparoscopic cholecystectomy is useful in preoperative evaluation of patients undergoing laparoscopic cholecystectomy, even if it not infrequently fails to predict the surgically difficult cases mainly due to adhesions around the gallbladder. PMID- 8463614 TI - Percutaneous needle biopsy of hepatic cavernous hemangioma. AB - In a retrospective review of percutaneous needle biopsy in 38 patients, we assessed the safety of this procedure for establishing the diagnosis of cavernous hemangioma of the liver. Computed tomography (CT) or ultrasound was used to direct the biopsy of focal liver lesions ranging in size from 1 to 13.5 cm, with a median size of 3 cm. In all patients, the pathological diagnosis was established conclusively on the basis of core tissue samples obtained using a 20 gauge cutting needle and an average of 2.7 passes. Biopsy was performed as an outpatient procedure in 31 patients (82%). Clinical or radiological follow-up of 30 patients for an average of 32 months (range 7-57 months) supported the pathological diagnosis of cavernous hemangioma. Despite the reported risk of hemorrhage, we performed biopsies on all patients without serious complication; five patients complained of transient right upper quadrant pain, that did not require treatment. We conclude that percutaneous needle biopsy (PNB) of the liver is a safe and effective procedure for establishing the diagnosis of cavernous hemangioma in patients who have no bleeding diathesis. PMID- 8463615 TI - Carcinoid tumors of the gut. Our experience over three decades and review of the literature. AB - We review our institution's experience with gastrointestinal (GI) carcinoid tumors over the past three decades: fifty-five cases with complete follow-up. The majority of carcinoids were from the ileum and appendix--19 cases (35%) and 17 cases (31%), respectively. Other locations included the cecum in five (9%), duodenum in three (5%), jejunum in three (5%), rectum in three (5%), and pylorus in one (2%). Four patients had metastatic carcinoid of uncertain primary (7%). Appendiceal carcinoids were frequently incidental and small (all < 1 cm). None were metastatic, and all appeared to have been cured with simple appendectomy. In contrast, ileal carcinoids were usually symptomatic and often metastatic at the time of diagnosis. Carcinoid syndrome occurred in 10 patients (18%), associated primarily with metastatic tumors from the ileum and cecum. Secondary malignancies were seen in 10 patients (18%). We provide a literature survey of GI carcinoid tumors and carcinoid syndrome. PMID- 8463616 TI - Fatal gastroduodenal necrosis after injection sclerotherapy for bleeding duodenal ulcer. AB - Complications after endoscopic injection therapy to control bleeding from peptic ulcers are uncommon and rarely fatal. We report a case of fatal gastroduodenal necrosis and postulate that accidental intra-arterial injection may be responsible for this event. PMID- 8463617 TI - Crohn's disease of the gallbladder. AB - In a 57-year-old woman, Crohn's disease involving the gallbladder and duodenum caused biliary tract obstruction and necessitated surgery. The patient's symptoms did not improve postoperatively until corticosteroids provided rapid resolution. Inflammatory bowel disease often involves the hepatobiliary tree, yet the gallbladder is rarely involved directly. This patient highlights a rare complication of Crohn's disease. PMID- 8463618 TI - Metastatic prostate cancer simulating sclerosing cholangitis. AB - We report what we believe to be the first case of metastatic prostate cancer presenting as sclerosing cholangitis. In a 71-year-old man with known prostate cancer and cholestatic jaundice, an endoscopic retrograde cholangiopancreatography revealed multifocal strictures of both the intrahepatic and extrahepatic biliary system consistent with sclerosing cholangitis. Review of a liver biopsy and cholecystectomy specimen showed metastases from prostate cancer, which stained positively with prostate-specific antigen. Multiple hepatic metastases from prostate cancer should be included among the conditions that simulate primary sclerosing cholangitis on cholangiography. PMID- 8463619 TI - Primary Sjogren's syndrome associated with chronic atrophic gastritis and pernicious anemia. AB - Sjogren's syndrome (SS) is a systemic, autoimmune exocrinopathy in which destructive, inflammatory-cell infiltration can affect any gland. Although chronic atrophic gastritis is the most common form of gastrointestinal involvement in SS, pernicious anemia develops in rare cases. We therefore report a patient with these three associated diseases. PMID- 8463620 TI - Open access endoscopy: a large-scale analysis of its use in dyspeptic patients. AB - We examined 2,253 consecutive dyspeptic patients referred to our endoscopy service by general practitioners ("open" group) and hospital clinicians ("clinic" group) to study the prevalence of the various endoscopic findings according to patient age and the route of endoscopic referral. The results obtained are representative of that specific population. Normal endoscopic findings progressively lessened as patients' age increased, and the overall rate was as low as 26.5% in the open and 30.3% in the clinic groups. Erosive prepyloric changes and duodenitis were the most frequently noted abnormalities in patients < 40 years of age (16.9% and 20.1%, respectively, in the open and 11.6% and 14.2% in the clinic groups). Chronic gastritis was prevalent in patients > 60 years of age. Duodenal ulcer decreased from 9.7% (open) and 18% (clinic) in patients < 40 to 2% and 1.1% in patients > 60. No malignancy was found in patients < 40, while only approximately 1% of those < 60 had neoplasms. All our endoscopic findings, both in the open and the clinic groups, were not significantly different. No significant differences in symptoms were observed among patients with different endoscopic findings. We conclude that (a) endoscopy is really useful only in a small group of patients < 40 years of age; (b) individual symptoms alone have a poorly discriminant diagnostic power; and (c) restriction of open access endoscopy is not justified. PMID- 8463621 TI - Assessment of portal contribution to liver perfusion by quantitative sequential scintigraphy and Doppler ultrasound in alcoholic cirrhosis. Diagnostic value in the detection of portal hypertension. AB - To assess the portal contribution to liver perfusion, we carried out quantitative sequential scintigraphy in 110 patients with alcoholic cirrhosis (22 Child-Pugh class A, 39 class B, 49 class C) and 15 normal subjects. Duplex Doppler ultrasound found a type of intrahepatic circulation that made the standard scintigraphic procedure inaccurate in four cases of cirrhosis, which were reevaluated. Portal contribution to liver perfusion was lower in cirrhotics than in normal subjects (48.7 +/- 29% versus 78.4 +/- 6%; p < 0.001). The sensitivity of scintigraphy in detecting portal hypertension, based on portal contribution < or = 66%, was 61.8% (with a 100% specificity) compared with 66.7% for endoscopy (diagnosis based on existence of varices). The overall sensitivity of the two tests together was 86.1%. Portal contribution to liver perfusion was inversely correlated to Child-Pugh score (r = 0.53; p < 0.001), to prothrombin time (r = 0.52; p < 0.001), and to hepatic venous pressure gradient (r = 0.43; p < 0.001) and positively correlated to albuminemia (r = 0.42; p < 0.001). Concurrent alcoholic hepatitis and the existence of large portosystemic collaterals were related to a decrease in portal contribution to liver perfusion. We conclude that quantitative sequential scintigraphy, which shows a direct relationship between portal contribution to liver perfusion, on the one hand, and the amount of portosystemic shunting, the progression of liver disease, and/or acute liver injury, on the other, could serve as a diagnostic test for portal hypertension. The addition of scintigraphy improves the overall sensitivity of endoscopy. PMID- 8463622 TI - Hepatic hemangioma showing a mass effect on the stomach wall: endosonographic differentiation from submucosal tumor of the stomach. PMID- 8463623 TI - Rectal Hodgkin's disease in acquired immune deficiency syndrome. PMID- 8463624 TI - Metastases of a gastric adenocarcinoma to the rectum. PMID- 8463625 TI - Diarrhea, constipation, and hypothyroidism. PMID- 8463626 TI - Red jello stool and red dye-arrhea. PMID- 8463628 TI - Read my lips revisited. PMID- 8463627 TI - CEA in gastric juice and chronic atrophic gastritis: a prospective evaluation. PMID- 8463629 TI - "Not so easy to diagnose" dyspepsia. AB - The diagnosis of the cause of a dyspepsia should not rest on indiscriminate "routine" investigation. It should be based on historical and physical evidence supported by a therapeutic trial that confirms the clinical diagnosis. If necessary, it should be followed by selected investigations to confirm or exclude serious diseases that are likely to be the cause of the symptoms. If an organic explanation cannot be provided, it should not be assumed that one does not exist, only that the more serious and treatable causes have been excluded. "Sophisticated" high-technology investigations should not become part of the "routine" investigation of dyspepsia. PMID- 8463630 TI - Celiac (solar) plexus syndrome. A frequently overlooked source of abdominal pain. AB - Of the nonorganic abdominal disorders the celiac/solar plexus syndrome represents a frequently seen entity characterized by the typical association of epigastric pain and "lambda-type" tenderness. It is a special type of abdominal neurosis in which the pain arises in the periaortic nervous plexuses. Its clinical importance is in the differential diagnosis, since it is often misinterpreted as a painful condition of abdominal or retroperitoneal origin. PMID- 8463631 TI - Cervical dysphagia is associated with gastric hyperacidity. AB - There is some controversy regarding the association of upper esophageal symptoms and acid gastroesophageal reflux. We carried out gastric acid analysis, 24-h esophageal pH measurement, and esophageal manometry in 150 patients with symptoms suggestive of gastroesophageal reflux disease. Of these, 22 (15%) had gastric acid hypersecretion [basal acid output level > 5 mmol/h (19 patients) or maximum acid output level > 30 mmol/h (13 patients)]. They were compared to 25 consecutive patients with normal gastric acid secretion. An incompetent lower esophageal sphincter was identified in a similar number of hypersecretors (HS) (59.1%) and normosecretors (NS) (44%). Esophageal acid exposure was more common in HS than in NS (score, 70 vs. 36.1, p < 0.05). This was reflected as a higher incidence of esophagitis in HS (67 vs. 14%, p < 0.0025). Symptoms of cervical dysphagia were present in eight of 22 HS and one of 25 NS (p = 0.009). There was no anatomical lesion on endoscopy to explain the dysphagia. Upper esophageal sphincter (UES) manometry showed normal pharyngeal pressure, resting UES pressure, and length in both groups. The mean closing UES pressure was 127 mm Hg in HS and 114 mm Hg in NS (0.1 > p > 0.05). The HS with cervical dysphagia were no different from HS without dysphagia in any respect. We conclude that patients with gastric acid hypersecretion have more acid reflux, esophagitis, and cervical dysphagia. This is not associated with demonstrable abnormality in stationary manometry. Prolonged measurement may be required to show any change. PMID- 8463632 TI - A medical sociologist looks at health promotion. PMID- 8463633 TI - Examining HIV-related knowledge among adults in the U.S. AB - Supplemental AIDS data from the 1987 National Health Interview Survey indicate that adults in the U.S. know the most frequent modes of HIV transmission, but lack a more comprehensive understanding of HIV and AIDS. Elements from a diffusion model were isolated to create a path-analytic framework for examining the effects of population or recipient characteristics and information sources or communication channels on HIV-related knowledge with these data. This multivariate analysis suggests that persons of lower socioeconomic status, older adults, those from racial/ethnic minority groups, those living outside of metropolitan areas, men, and those citing mass media (television or newspapers) as their primary source of information about HIV and AIDS have slightly lower levels of HIV-related knowledge. Decomposition of the effects in the path analysis suggests that use of information sources or channels, as measured by survey data, accounts for little of the observed variation in HIV-related knowledge. The implications of these results for future research and HIV-related education are discussed. PMID- 8463634 TI - Determinants of social support among gay men: the context of AIDS. AB - In this study, the determinants of social support are examined among a probability sample of gay men residing in San Francisco. Using two waves of data (collected in 1985 and 1987), cross-sectional and longitudinal analyses focused on the effects of five sets of factors (demographic, community integration/network, AIDS-related loss, individual, and health) on satisfaction with three types of support (emotional, informational, and practical). Personal acceptance of one's gay identity and talking to family members about AIDS showed the strongest positive associations with concurrent measures of support and changes in support satisfaction over the two-year period. Conversely, depression and number of HIV symptoms were negatively associated with cross-sectional support and support changes. Family knowledge of respondents' homosexuality interacted with HIV symptoms, such that knowledge was negatively associated with support among those experiencing greater numbers of HIV symptoms. Findings suggest that those most in need of support may be the least satisfied with the support they receive. Family appear to have the potential to be particularly helpful or especially harmful to gay men trying to cope with the AIDS crisis. PMID- 8463635 TI - Stress, role captivity, and the cessation of caregiving. AB - Difficulties experienced when caring for an impaired elderly relative, including decisions to place this person in institutional care, are examined as a function of caregiver stress. Three annual interviews were conducted with 555 caregivers to parents or spouses with Alzheimer's Disease. All patients were initially cared for at home, but 192 were subsequently placed in institutional care and 146 died. Background-contextual factors and disease characteristics have only limited associations with institutionalization. Two secondary stressors--consequences of caregiving that do not directly involve care-related tasks--exert the most proximal impact upon placement: role captivity and economic strain. Role captivity is stable over time when in-home care continues, but institutionalization alleviates this sentiment. The odds of patient death increase substantially following institutionalization, even when health status is controlled. These results illustrate that in-home care may be beneficial for care recipients, but increase role-related stress for the care provider. PMID- 8463636 TI - Monitoring AIDS and other rare population events: a network approach. AB - This paper replicates and extends an earlier attempt to use data from the General Social Survey (GSS) to track the distribution of AIDS across demographic subgroups. (The GSS asks respondents whether they know a person with AIDS [PWA].) The gender, racial, age, and regional composition of the set of PWAs reported by GSS respondents is compared with that of the official AIDS cases reported to the Centers for Disease Control (CDC). In an attempt to assess the accuracy of the GSS estimates, a similar analysis is performed in which GSS respondents are asked whether they know a homicide victim. Data from four consecutive GSS samples (1988, 1989, 1990, and 1991) are used, permitting a more detailed exploration of potential biases and problems with the network technique. In addition, time series data from the National Health Interview Survey on the percentage of people who know at least one PWA are used to validate the GSS data. Our earlier findings, that the GSS identifies proportionately more White and midwestern cases than are reported to the CDC, are corroborated by the additional data. Possible explanations for these discrepancies are given, and suggestions are made for improving the utility of the approach. PMID- 8463637 TI - Husband and wife differences in response to undesirable life events. AB - In the present study of 451 married couples living in the rural midwest, gender differences were examined in reports of exposure and vulnerability to specific types of undesirable life events. Consistent with expectations derived from either a social structural or identity perspective, the results demonstrated that men are more likely than women to report exposure to and to be distressed by work and financial events. Women, on the other hand, are more strongly influenced by exposure to negative events within the family but not within their network of friends. Outcomes vary according to the type of emotional distress. Financial stress, for example, increases hostility among men more than among women, but wives are more likely than husbands to report somatic complaints in response to the same stressor. The findings demonstrate the need for future research that more directly investigates the intraindividual and social mechanisms which account for gender differences in a broad range of emotional and behavioral responses to varying types of significant life changes. PMID- 8463638 TI - Each Medicare carrier has been directed to establish a physician advisory committee. PMID- 8463639 TI - Health care reform should begin with insurance industry. PMID- 8463640 TI - Just say 'no' to 'trips'. PMID- 8463641 TI - Reversing the decline and fall of the general internist. PMID- 8463642 TI - Medicaid rescue effort to be 'painful'. Interview by Bob Carlson. PMID- 8463643 TI - HIV seroprevalence in the Bell Flower STD Clinic. PMID- 8463644 TI - State program tracks Schedule II drugs. AB - By implementing the multiple copy prescription program, Indiana demonstrates its concern with the problems of doctor shoppers and physicians involved with abuse. By trying to track illegal diversion of Schedule II drugs, states that have implemented tracking programs are trying to rid the streets of illicit drug use. When it is time to renew the law, the state should consider using modern computer technology. Indiana's program could be even more effective if it incorporated electronic data transfer. PMID- 8463645 TI - Brain biopsy in Indiana AIDS patients. AB - The neuropathologic findings of brain biopsies in a series of Indiana AIDS patients were reviewed. All subjects displayed focal lesions on radiographic studies. The three most common diagnoses were toxoplasmosis, progressive multifocal leukoencephalopathy and primary central nervous symptoms (CNS) lymphoma. These findings were consistent with previous studies elsewhere. Biopsy appears to affect the course of treatment only if CNS lymphoma is discovered. Because the value of currently available therapy for this disease in AIDS patients is controversial, there is no clear consensus regarding the indications for biopsy in this population. PMID- 8463646 TI - From the museum. PMID- 8463647 TI - Diagnosis of infective endocarditis. AB - The diagnosis of IE is often difficult to establish with certainty. Current diagnostic criteria have several weaknesses, the most important being failure to utilize the results of echocardiography. This seems inconsistent with modern practice. In reality, the results of modern echocardiography, including appropriate use of transesophageal echocardiography, are critically important for diagnosis of infective endocarditis. New criteria are in the process of development which should prove more sensitive and more specific for disease classification, epidemiologic studies, and clinical trials. PMID- 8463648 TI - Aminoglycoside resistant enterococcal endocarditis. AB - There are few well-documented cases of infective endocarditis due to highly aminoglycoside-resistant enterococci reported to date. Nevertheless, strains with high-level resistance to both streptomycin and gentamicin are now sufficiently common that the number of cases of endocarditis due to these organisms will undoubtedly continue to increase. Serious efforts to develop appropriate alternative treatment strategies are now clearly necessary. All high-level gentamicin-resistant bloodstream isolates from patients with suspected or proven endocarditis should be screened for high-level streptomycin resistance. Because these two resistance traits are mediated by distinct genetic elements, a significant minority of highly gentamicin-resistant enterococci will be susceptible to synergistic killing by combinations of cell wall-active antibiotics with streptomycin. For strains highly resistant to both aminoglycosides, there is no evidence of benefit from use of these toxic antimicrobials, and treatment with a cell wall-active agent alone is warranted. Based on older literature and animal models, perhaps as many as 40% to 50% of cases of enterococcal endocarditis might be curable by such regimens. Alternative combinations using a cell wall-active antibiotic together with a fluoroquinolone or rifampin cannot be specifically recommended based on any firm data from the literature, but possible merits of such combinations can be explored in vitro under appropriate circumstances. For ampicillin- and vancomycin-susceptible strains, ampicillin would seem preferable because this drug typically demonstrates greater bactericidal activity in vitro as a single agent. Consideration could be given to administration of ampicillin by continuous intravenous infusion. Several animal studies indicating effectiveness of penicillins for enterococcal endocarditis have used dosing regimens resulting in sustained serum levels. It is unknown whether these observations are relevant to human enterococcal infections. Testing for beta-lactamase production should be undertaken if penicillins are to be used. For strains that are resistant to achievable concentrations of penicillins, or when the patient is intolerant of beta-lactams, vancomycin can be used. In animal models, teicoplanin has appeared to be superior to vancomycin, but high concentrations must be attained. This drug is not yet approved for clinical use, however, and it is unclear if any advantage would exist in treatment of human infections. The recent emergence of enterococci which are resistant to glycopeptides has introduced another potential complicating factor; some of these are also substantially resistant to beta lactams as well. In some reports, favorable interactions between vancomycin and beta-lactams have been observed against vancomycin-resistant strains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463649 TI - Zoonotic endocarditis. AB - The so-called zoonotic endocarditis is transmitted from animals to humans and is frequently found in some cattle-raising countries. Brucella endocarditis is a destructive process of the aortic valve with abscess formation that commonly leads to heart failure. Q fever endocarditis is a more indolent infection, but it is also capable of producing severe valvular damage and hemodynamic compromise. Treatment of zoonotic endocarditis includes the prolonged administration of doxycycline in combination with other antimicrobial agents and a judicious use of valve replacement. Mortality of Brucella endocarditis has been decreased significantly by a medical-surgical approach to treatment. On the basis of serologic and valve tissue culture results, no treatment is consistently able to cure Q fever endocarditis, and thus mortality of this infection remains high. PMID- 8463650 TI - Management of complications of infective endocarditis with emphasis on echocardiographic findings. AB - This article reviews in brief the basic principles of echocardiography and their application in infective endocarditis. The role of echocardiography in relation to surgical decision making is emphasized. The special problems of vegetations, valve ring abscess, leaflet perforation, prosthetic valve endocarditis, and infective endocarditis in congenital heart disease are reviewed. PMID- 8463651 TI - Adherence events in the pathogenesis of infective endocarditis. AB - Infective endocarditis begins with adherence of microorganisms to cardiac tissues. These tissues have often been previously damaged, creating a thrombotic lesion consisting of platelets and fibrin. Circulating microorganisms localize to this lesion. The tissue specificity of endocarditis likely results from interactions between cell-surface determinants on the endocardium, platelet, and microorganism. Interference with these binding events may offer a means of modifying the course of the infection. PMID- 8463652 TI - Pharmacokinetic and pharmacodynamic aspects of therapy of experimental endocarditis. AB - Bacterial endocarditis is difficult to cure because of poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response, that could cooperate with antibiotic action. Two main aspects are discussed for their effect on human therapy: (1) the kinetics of antibiotic diffusion into vegetations, with a special reference to the data obtained with autoradiography, and (2) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis, including the clinical consequences of these two parameters on antibiotic dosing regimens and length of therapy. PMID- 8463654 TI - Short-course combination and oral therapies of Staphylococcus aureus endocarditis. AB - The experimental basis for use of 2-week semisynthetic penicillin plus aminoglycoside combination therapy for Staphylococcus aureus endocarditis is reviewed. The use of oral therapy is examined. Short-course combination of oral regimens can be effective and may be suitable for selected patients with S. aureus endocarditis. PMID- 8463653 TI - Staphylococcus aureus bacteremia and endocarditis. New diagnostic and therapeutic concepts. AB - Staphylococcus aureus is an important and prevalent cause of both uncomplicated bacteremia, as well as endocarditis. This article addresses the following controversial strategies: diagnosis of endocarditis in staphylococcemic populations; optimal treatment strategies for right-sided and left-sided S. aureus endocarditis; use of echocardiography in S. aureus endocarditis; and therapy options for catheter-associated staphylococcemias. PMID- 8463655 TI - Endocarditis due to coagulase-negative staphylococci. Microbiologic, epidemiologic, and clinical considerations. AB - Coagulase-negative staphylococci are the most frequently isolated pathogens in prosthetic valve endocarditis and cause 5% of infections involving native valves. Distinguishing contamination from bacteremia may be challenging. The presence of heteroresistance in many strains makes rigorous susceptibility testing a requirement for selecting appropriate antibiotic selection. Infection is frequently complicated by valvular insufficiency with congestive heart failure, local tissue invasion or synthetic embolization, making surgical intervention necessary in many cases. PMID- 8463656 TI - Risk factors for infective endocarditis. AB - The incidence of endocarditis is increased in patients with cardiac lesions causing turbulent flow. A 400-fold increase is observed in patients with prosthetic valves and a prior history of endocarditis. Other high risk lesions include rheumatic valvular disease, cyanotic congenital heart disease, and degenerative valve lesions. The smaller increased incidence in patients with mitral valve prolapse is important because of the high prevalence of mitral valve prolapse in the population. In addition, intravenous drug use and nosocomial bacteremia have emerged as important factors among patients with endocarditis. PMID- 8463658 TI - Introduction ethics in orthopaedic surgery "these are the times that try men's souls". PMID- 8463657 TI - Ceftriaxone and outpatient treatment of infective endocarditis. AB - There are a total of 8000 cases of infective endocarditis yearly in the United States. Central nervous system metastatic infections are not uncommon in infective endocarditis. Because ceftriaxone is highly bound to serum proteins, there is concern that the drug is highly bound to serum proteins, there is concern that the drug might not penetrate well in the core of an infected vegetation. To date, there are two published studies on the treatment of nonenterococcal streptococcal endocarditis by ceftriaxone in humans. Ceftriaxone appears to be an attractive alternative antibiotic therapy to conventional regimens in the treatment of streptococcal endocarditis. PMID- 8463659 TI - The diabetic foot: diagnosis and prevention. AB - Diabetes remains the world's leading cause of amputation. Like many other major health problems, prevention is the key to successful management. Patient education efforts coupled with a team approach of aggressive early management represent the optimum current strategy. Multidisciplinary physician teams consisting of orthopaedic and vascular surgeons, supported by consultation, serve as the focus for leadership and decision making. Their efforts are supported by allied health personnel, nurses, physician's assistants, and physical therapists trained in foot evaluation, pedicare, and nail trimming, assisted by competent trained shoe technicians, orthotists, or pedorthists. At each visit the patient is examined, footwear is evaluated, and ongoing education is provided. Visits are scheduled according to a risk protocol, and treatment is based on problem classification. This regimen should result in increased patient compliance and overall improved patient care. PMID- 8463661 TI - The diabetic foot: Charcot arthropathy. PMID- 8463660 TI - Outpatient diagnosis and care of the diabetic foot. PMID- 8463662 TI - Surgical management of ulcers, soft-tissue infections, and osteomyelitis in the diabetic foot. PMID- 8463663 TI - Salvage of a functional lower limb in diabetic patients after amputation. PMID- 8463664 TI - The diabetic foot: evolving technologies. AB - Diabetic malperforans ulcers are extremely challenging problems, and their treatment requires a multidisciplinary approach. The wound management technique is based on the depth of ulceration; necrosis and infection should be aggressively managed. Wound healing and prevention of adjacent breakdown is best assured through casting and professional shoewear techniques. The vascular aspects of the patient's disease must be addressed. Patients failing this multidisciplinary team approach may be candidates for adjunctive management. If transcutaneous oxygen studies indicate diminished oxygen perfusion, hyperbaric oxygen might be considered. Contraindications to this modality are certain pulmonary problems, including chronic obstructive pulmonary disease and pulmonary fibrosis. Some individuals, particularly those with claustrophobia, may find small hyperbaric chambers psychologically unacceptable. Studies on tissue and platelet growth factors are encouraging. Limited clinical experience with these materials has been encouraging and future clinical applications are anticipated; however, like hyperbaric oxygen, these growth factors are only an adjunct to a comprehensive foot care program. PMID- 8463665 TI - Functional nerve disorders in the athlete's foot, ankle, and leg. AB - Although neuropathies in the athlete's foot, ankle, and leg are uncommon, they are often underdiagnosed, primarily because of the complex interplay of causative factors. The physician should be aware of the possible occurrence of these neuropathies, and should be familiar with the anatomy and course of the nerves. Often, the problem only occurs during functional activity and cannot be demonstrated during the routine static examination. Other problems should also be considered when there is the possibility of a nerve compression syndrome. Metabolic processes, such as diabetes or abuse of alcohol, can certainly cause neuropathies. A double crush syndrome or pain from a higher source should also be considered. Finally, if surgery is done for chronic problems, only the area of constriction should be released, without interfering with the nerve itself. Release the fascia but leave the perineural fat intact. If instability is a factor, the joint should also be stabilized. PMID- 8463666 TI - Biomechanics of fractures and fracture fixation. PMID- 8463667 TI - The Jones fracture. AB - The Jones fracture is a fracture that occurs 1.5 cm distal to the styloid of the fifth metatarsal. The mechanism of injury in both the acute and chronic, or stress, fracture is repetitive weightbearing and pivoting on the involved foot. Acute fractures occur equally in both sexes, generally in nonathletes, and usually in individuals older than 21. Chronic or fatigue fractures occur in individuals between 15 to 21 years of age and predominantly in male athletes. Treatment of the acute fracture in the adult may require three months in a nonweightbearing cast. Surgical intervention with intramedullary screw compression is a surgical option that should be discussed with the patient. Chronic or fatigue fractures will require intramedullary compression screw fixation or open reduction and bone grafting using corticocancellous bone graft. The treatment outcome of this fracture is usually good if postoperative rehabilitation is prescribed and followed. PMID- 8463668 TI - Turf toe. PMID- 8463669 TI - Chronic exertional compartment syndrome. PMID- 8463670 TI - Foot orthoses. PMID- 8463671 TI - Mechanism, diagnosis, and treatment of running injuries. AB - Today running is an integral part of many people's lives. Despite an increased focus on the prevention of running injuries, overuse injuries are still rather frequent. It is important to identify the cause of the injury and treat the cause, not merely the symptoms. Of these injuries, 60% to 80% are associated with extrinsic factors, such as training errors and changes in running activities. Intrinsic factors are also common, especially malalignments, including excessive pronation and cavus foot. These changes are associated with common over-use injuries, but specific anatomic abnormalities and abnormal biomechanics of the lower extremity are not correlated with specific injuries on a predictable basis. Factors such as leg-length discrepancy, poor flexibility, muscle weakness and imbalance, deficit in neuromuscular coordination, and ligamentous laxity can also cause running injuries. Acquired or secondary factors, such as kinetic chain dysfunctions, are more common than previously acknowledged. Many running injuries, especially in patients with recurrent and previous injuries, are manifestations of a dysfunction of the kinetic chain. For this reason, it is important to examine the symmetry of stance and gait, and to look for abnormalities in both static and dynamic alignment and function. The whole kinetic chain must be carefully screened to rule out any underlying injuries or dysfunction. This process is difficult and requires experience and knowledge, especially because the cause of injury may be remote from the site of injury. The treatment of running injuries involves both a specific diagnosis, based on the primary problem, and the identification of kinetic chain dysfunctions. In order to be successful, treatment must be based on the specific diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463672 TI - The biomechanics of the acromioclavicular, sternoclavicular, and scapulothoracic joints. PMID- 8463673 TI - Shoulders: frozen and stiff. PMID- 8463674 TI - Acromioclavicular joint injuries. AB - The effective treatment of injury to the acromioclavicular joint requires knowledge of the relevant anatomy and the pathoanatomy of a variety of injury patterns. The six-part classification system facilitates the understanding of the underlying pathoanatomy. Insight into the natural history of acromioclavicular joint injury is crucial to the success of any treatment program. Surgical reconstruction should be reserved for patients with grade IV, V, and VI lesions or those with lower grade lesions that have become chronically symptomatic. If the decision is made to proceed with surgical reconstruction, I prefer coracoclavicular fixation, over-drilling the clavicle, and use of an AO 6.5-mm cancellous lag screw to maintain reduction of the clavicle, followed by careful repair of the overlying soft tissues. PMID- 8463675 TI - Fractures of the scapula. PMID- 8463676 TI - The treatment of nonunion fractures of the midshaft of the clavicle with an intramedullary Hagie pin and autogenous bone graft. PMID- 8463677 TI - Reconstruction of the infected total hip and knee arthroplasty with gentamicin impregnated Palacos bone cement. PMID- 8463678 TI - Compression plate fixation and the effect of different types of internal fixation on fracture healing. PMID- 8463679 TI - Patellofemoral complications of total knee replacement. AB - Patellofemoral complications account for the majority of problems following total knee replacement. Many of these problems are technical, and attention to detail at the time of surgery can help avoid them. An understanding of the potential postoperative complications should help one to diagnose these early and prevent catastrophic problems. PMID- 8463680 TI - Unicompartmental knee arthroplasty. PMID- 8463681 TI - Principles of condylar knee arthroplasty: issues evolving. PMID- 8463682 TI - Revision knee arthroplasty technique. PMID- 8463683 TI - Alternatives to reimplantation for salvage of the total knee arthroplasty complicated by infection. PMID- 8463685 TI - Osteochondral allografts. PMID- 8463684 TI - The economic impact of infected total joint arthroplasty. AB - Infection in total joint replacement is a devastating and life-threatening complication for the patient. It can also be an economic disaster for hospitals that treat large numbers of these patients. The most important factor in both the clinical and economic area is to prevent the infection from occurring at all. However, once deep infection is established, rapid, aggressive, and definitive treatment must be rendered to the patient. A method of case-sharing must be established by medical centers that are best equipped to care for these patients. Reimbursement to hospitals and physicians must more realistically reflect the magnitude of resources consumed by these patients and the time-consuming and intensive care provided by a team of physicians. PMID- 8463686 TI - Principles and techniques of tissue banking. PMID- 8463687 TI - Revision arthroplasty using allograft bone. PMID- 8463689 TI - Bone grafting in revision cementless total knee arthroplasty. PMID- 8463688 TI - Allograft reconstruction of the anterior and posterior cruciate ligaments: report of ten-year experience and results. PMID- 8463690 TI - Use of allografts following resection of tumors of the musculoskeletal system. AB - Allografts are an effective method of reconstructing defects following the resection of benign or malignant tumors. The surgeon must carefully plan the procedure in two stages. Stage I involves resection of the tumor with an adequate margin to prevent local recurrence, and stage II involves reconstruction of the limb with a durable and functional technique that has a low risk of morbidity. Allograft reconstructions are technically demanding. The prerequisites to a successful reconstruction include rigid internal fixation of the allograft, competent soft tissues to cover the graft, preoperative and postoperative antibiotic coverage, meticulous hemostasis and postoperative wound drainage to prevent hematoma formation, and protection of the allograft to allow union. Whenever soft-tissue coverage of the graft is in question, local rotational flaps or free microvascular transfers should be used to cover the allograft with healthy muscle. Second surgical procedures, such as revision of necrotic soft tissue flaps, drainage of hematomas, bone grafting of nonunions, and revision of internal fixation, should be avoided by careful technique at the index operation because additional procedures place the allograft at risk for infection. Further basic science investigations and clinical studies should expand the applications of allograft reconstructions and lower the incidence of complications. PMID- 8463691 TI - Paget's disease of bone: pathophysiology and diagnosis. PMID- 8463692 TI - Medical treatment for Paget's disease of bone. PMID- 8463693 TI - Physical agents in musculoskeletal problems: heat and cold therapy modalities. PMID- 8463694 TI - Electrical stimulation of soft tissues. AB - It is well-documented that electrical potentials normally are present in biologic soft tissues. The discovery of these has generated interest in effecting a change in the biology of these tissues by externally imposing an electrical field. There is experimental evidence that ligament and tendon repair can be affected by ES, but there have been no clinical studies to demonstrate its effectiveness in human ligament or tendon injuries. The only clinical support for use of ES to enhance soft-tissue healing is for its use in chronic, open dermal wounds. ES has been shown to be effective for these chronic wounds under certain conditions. There is currently insufficient justification for the use of ES for reduction of soft tissue edema. PMID- 8463695 TI - The modality of therapeutic exercise. PMID- 8463696 TI - Spinal considerations in the young athlete. AB - The young athlete involved in modern sports activity may be subject to considerable problems involving the spine. An appreciation of the differences in spinal anatomy, development, and kinematics facilitates the evaluation of each individual. While a variety of factors are operant that could contribute to difficulty in evaluation and treatment, an organized approach with an emphasis on naturally-occurring variations of the immature spine will allow for appropriate recommendations. While concern exists regarding the individual with congenital, developmental, or hereditary conditions, it is important to respect the individuality of these young athletes and to assess each problem in a comprehensive manner before recommending full or restricted activity. Current research should yield important information that will serve as more absolute guidelines in formulating recommendations for involved adolescent athletes and will establish the natural history of conditions that today remain obscure. PMID- 8463697 TI - Acute knee injuries in the immature athlete. PMID- 8463698 TI - Knee overuse disorders in the pediatric and adolescent athlete. PMID- 8463699 TI - Adolescent anterior knee pain. PMID- 8463700 TI - Congenital dislocation of the knee and patella. PMID- 8463701 TI - Infantile tibia vara. PMID- 8463702 TI - Varus foot in cerebral palsy: an overview. AB - In cerebral palsy, imbalance of the invertor and evertor muscles can result in varus alignment of the foot. The primary functional problems of varus foot are weightbearing instability and/or difficulty in foot clearance in swing phase. Additional problems include difficulties in shoe fitting, abnormal shoe wear, and unacceptable cosmesis. Gait studies have shed some light on the alterations of the muscle activity that can cause this problem but have fallen short of providing clear guidelines for treatment of this common problem. Confusion exists because dynamic electromyography does not give definitive information about the quantity of muscle tension and because the analyses have not included movement measurements that distinguish between the movements that occur in the hind foot and forefoot. Technical limitations that have made it impossible to obtain this information are rapidly disappearing, and the way is opening up for biomechanical studies of foot and ankle function that will allow greater precision in the selection of surgical treatment for varus foot. PMID- 8463703 TI - Discrepancies in the orthopaedic literature: why? A statistical explanation. PMID- 8463704 TI - Flexible intramedullary nailing of long bone fractures. PMID- 8463705 TI - Distal radius fractures: nonsurgical treatment options. AB - In conclusion, each of these methods have been proven to be effective in selected patients. None of these methods, however, can be used in all patients. They must be carefully evaluated for use in young patients where anatomic alignment is essential to avoid impairment of function with loss of grip strength and the possibility of developing post-traumatic arthritis. If any of these methods is used, ideal cases would be those with nonarticular fractures, with minimal displacement and minimal bone loss, and some assurance that the fracture will remain stable during treatment. The techniques have been proven to be effective. If, however, fracture reduction is lost with any of these techniques, one must reassess the fracture, especially in the young, and be more aggressive in restoring and maintaining alignment until healing has occurred. Orthopaedic Knowledge Update 3, published in 1990, relates, "Depending on comminution, fixation may be best achieved with plate, screws, Kirschner wires, external fixation or some combination of these." It goes on to state, "In young adults particularly, accurate reduction of the articular surface appears critical to achievement of a good result after a Colles' fracture." PMID- 8463706 TI - Fractures of the distal radius: operative treatment. PMID- 8463707 TI - Malunion of the distal radius: current approach to management. PMID- 8463708 TI - Polypeptides synthesized in vitro by Biomphalaria glabrata hemocytes bind to Schistosoma mansoni primary sporocysts. AB - In vitro labeled polypeptides secreted by schistosome-susceptible and -resistant Biomphalaria glabrata were tested for their ability to bind the surface tegument of Schistosoma mansoni primary (= mother) sporocysts. Out of a complex pattern of SDS-PAGE-separated hemocyte polypeptides, only two (19 and 46 kDa) bound to sporocysts. The 19-kDa polypeptide consistently bound to both live and fixed sporocysts, although fixed larvae usually bound more than living sporocysts. The 46-kDa component bound primarily to fixed sporocysts. A similar pattern of binding was seen when sporocysts were exposed to polypeptides secreted into culture medium by both resistant and susceptible snail hemocytes. However, previous work indicates that sporocyst secretory products, in the presence of homologous snail plasma components, can differentially influence the quantity of these two polypeptides. Therefore, it is hypothesized that "regulation" of the interaction of snail hemocyte polypeptides with the parasite may lie in the sporocyst-mediated differential effect on synthesis and/or secretion of the 19- and 46-kDa polypeptides by hemocytes of these two snail strains. Thus, the hemocyte polypeptides reported in this study may represent potential mediators of self/non-self-recognition or hemocyte activation in the B. glabrata internal defense system. PMID- 8463710 TI - Effect of Beauveria bassiana and Candida albicans on the cellular defense response of Spodoptera exigua. AB - A marked difference in the cellular response of Spodoptera exigua was observed when larvae were challenged with the insect mycopathogen Beauveria bassiana versus the yeast Candida albicans. Both fungi were rapidly phagocytized by circulating hemocytes. The relative growth rate of C. albicans as measured by daughter cell formation was partially suppressed, whereas B. bassiana blastospores produced germ tubes at rates equivalent to those under in vitro conditions. Limited growth by C. albicans within the phagocytic cells stimulated nodulation by hemocytes resulting in the protection of challenged larvae to C. albicans. Alternatively, B. bassiana suppressed the spreading ability of S. exigua hemocytes. These suppressed larvae, while capable of phagocytizing C. albicans, were unable to produce multicellular nodules. Circulating vegetative cells of both C. albicans and B. bassiana were observed to proliferate within these immunosuppressed host larvae. PMID- 8463709 TI - Toxicity and pathology of crude broth filtrate produced by Hirsutella thompsonii var. thompsonii in shake culture. AB - Metabolic products secreted by the fungal mycelia of Hirsutella thompsonii var. thompsonii (CBS 556.77D) in a defined culture broth in shake culture were tested for toxicity to Galleria mellonella larvae and Drosophila melanogaster adults via injection and per os application, respectively. In addition, the toxic effect of broth filtrate was observed in vitro in a cell line of Bombyx mori. Czapek-Dox broth fortified with 1% yeast extract stimulated more rapid mycelial growth and correspondingly more toxin production in time. At 25-30 degrees C, metabolic toxin(s) was detected in broth via bioassay at about 4-5 days postinoculation when mycelial biomass reached 5 mg/ml (dry wt). At these temperatures, biological activity of the filtrate peaked at about 8-10 days when mycelial growth reached a maximum (10 mg/ml, dry wt). This suggests a positive relationship between toxic metabolite and mycelial production. After 10 days, the toxicity of the filtrate appeared to decline gradually. Pathogenicity symptoms of the metabolites developed slowly in both G. mellonella and D. melanogaster. Early signs of lethargy appeared at 4 days postinjection and cumulative mortality of G. mellonella larvae was low after 1 week; however, the percentage of mortality reached 98-100% after 14 days. At death, G. mellonella larvae displayed small dark spots on a brownish cuticle. Histopathological effects were observed in the larval midgut, malpighian tubules, hypodermis, fat body, hemocytes, muscle, and silk glands. Cellular change consisted of pycnosis of the nucleus and a reduction in cytoplasm density. Highest mortality (78.8%) to adult D. melanogaster occurred after 10 days post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463711 TI - Transfer of incompatibility factors between stocks of Nasonia (= Mormoniella) vitripennis. AB - The stock of Nasonia vitripennis marked by the nuclear eye color mutation "tinged" (ti) shows nonreciprocal cytoplasmic incompatibility with wild-type (+) strains. Homogenates prepared from ti female pupae and injected into + female pupae caused 39% of the recipients to acquire the incompatibility characteristics of the ti donors. When eggs obtained from ti females were fragmented and injected into + female pupae, or when the ti egg cytoplasm was injected into chick eggs and yolk sac homogenates were subsequently injected into + female pupae, 28% of the recipients acquired ti-type incompatibility characteristics. Results from passage of the egg cytoplasm through 0.23-microns millipore filters showed successful transfer of the incompatibility and suggest that the incompatibility system in N. vitripennis has two components: a bacterium and a smaller agent. PMID- 8463712 TI - Symposium on early leprosy. PMID- 8463713 TI - Primary involvement of scrotal skin in indeterminate leprosy. PMID- 8463714 TI - National strategy for elimination of leprosy in India. PMID- 8463715 TI - Variables influencing regularity of treatment. PMID- 8463716 TI - Dr. S.N. Ganapati. PMID- 8463717 TI - Meeting of the Leprosy Working Group of Rehabilitation International held on 9th Sept. 1992 at Nairobi, Kenya. PMID- 8463718 TI - Suspicious lesions and their diagnosis. PMID- 8463719 TI - Workshop on "MDT experiences and incidence trends" at Chilakalapalli (AP) on 14 15, June 1992. PMID- 8463720 TI - Role of histopathology in the early diagnosis of leprosy. PMID- 8463721 TI - Animal models for early leprosy. PMID- 8463722 TI - Early diagnosis of leprosy under field conditions. PMID- 8463723 TI - Does serology help in diagnosing early leprosy? PMID- 8463724 TI - Mycobacterium leprae soluble antigen (Rees) skin test responses in an endemic population in India. AB - The response to intradermal administration of Rees soluble skin test antigen was studied in 12,142 randomly selected individuals living in a highly endemic area in South India. Taking a cut-off point of 12 mm induration as the criterion for 'positivity', 73% of PB cases, 45% of MB cases and 63% of noncase population (67% in contacts and 63% in non-contacts) were found to be positive. Age-specific positivity rates were higher in males than in females and in adults than in children. The difference in age-adjusted positivity rates between cases, contacts an noncontacts in the female population was found to be significant. However, the differences in reaction response are not sufficient to identify the sub populations of cases, contacts and noncontacts and as such this antigen is not likely to be useful in epidemiological studies of infection and evolution of clinical disease in high endemic populations. PMID- 8463725 TI - Women and leprosy in Turkey. AB - Women in Turkey have many social, cultural and economical problems. Women with leprosy have problems in common with other women as well as those related to physical and social consequences of leprosy. There are 2,414 patients with leprosy in Turkey, registered to Istanbul Leprosy Hospital and 829 of them are females. The mean age and duration of disease of our female leprosy patients are high. Most women with leprosy were born in eastern part of Turkey where prevalence of leprosy is higher and most have moved to western regions. The proportion of women who have some kind of social security is very low. Their economic status is also not good and 79% of patients had stigma about their disease. Three fourths of these cases have been hospitalized some time, for different reasons. Most of them (97.2%) have inactive disease at present. Disability degrees of patients are high. Patients with disability degrees over one constitute 54% of total for eyes, 55% for hands and 51% for feet. High percentage of multibacillary form and long duration of disease, delayed diagnosis, insufficient self-care of patients due to low socio-economic and cultural status and failure of health personnel to control patients periodically may be among the reasons for such high ratios of moderate and severe disabilities. In the light of the data obtained in our study, some measures to alleviate the problems of patients resulting from their socio-economic, cultural and social status have been suggested. PMID- 8463726 TI - Fluoroquinolones and their adverse effects. PMID- 8463727 TI - Health and human resource mobilization: an assessment of staffing pattern in NLEP at operational level. AB - In this paper the staffing pattern, training and infrastructural facilities of the National Leprosy Eradication Programme (NLEP) at operational level as well as the attendant problems in mobilising human resources are discussed. The study shows that the major portion of the work of the NLEP is being shared by the PMWs (72%), followed by NMS (14%) and Medical Officers (5%). The population served by the PMW in all the high and moderate endemic regions is more than the prescribed limit except in Nagaland and Sikkim. In the same areas, the Medical Officer serves a population more than the norm in Andhra Pradesh, West Bengal, Maharashtra, Karnataka and Bihar. Regarding case load, in no state the M.O. serves more than 2500 cases except in Bihar and Kerala, in moderate endemic and low endemic regions respectively. The PMW in Haryana and Punjab states attends more than 250 cases. In NLEP every one out of four sanctioned posts is vacant. There is also an urgent need to rationalize the training programme so that there is optimal utilization of the training centres. PMID- 8463728 TI - Detection of antibodies to phenolic glycolipid by ELISA in leprosy patients. AB - Antibody (IgM) response to PGL-1, a surface glycolipid unique to Mycobacterium leprae has been studied in 25 cases each of lepromatous and tuberculoid leprosy and in 25 healthy controls. The absorbance value at 488 nm was expressed as antibody titre. Serum antibody titre was found to be significantly higher in patients than controls. Results confirm that antibody response in leprosy patients depend upon bacterial load. PMID- 8463729 TI - Intraocular pressure reduction and systemic absorption of timolol after administration of one side-coated inserts in rabbits. AB - The object of this study was to test whether flat, circular ophthalmic inserts releasing drug only from one side, would show improved activity parameters and reduced systemic absorption. To this purpose, uncoated and one-side coated hydroxypropylcellulose inserts containing timolol were prepared and evaluated. An acrylic copolymer (Eudragit RS) was used as coating material. Timolol release from inserts was studied both in vitro and in vivo. Timolol release in vitro from the coated inserts was much slower than from the uncoated ones, due to the smaller releasing surface area. Compared with timolol eyedrops (0.5%, 50 microliters), administration of 250 micrograms of timolol in uncoated or coated inserts produced a significantly greater hypotensive effect at 6 and 8 hr post instillation in rabbits with artificially increased intraocular pressure. The coated inserts containing 62.5 micrograms of timolol antagonised isoproterenol induced ocular hypotension significantly more than timolol eyedrops (0.5%, 12.5 microliters) and uncoated inserts containing 62.5 micrograms of timolol. Both uncoated and coated inserts provided a significant sustaining of timolol release in tear fluid and decreased systemic peak concentrations of timolol with respect to the eyedrop control. However, one-side coated inserts failed to show significant improvements with respect to the uncoated samples. PMID- 8463730 TI - Iontophoresis of reactive black 5 for pulsed dye laser sclerostomy. AB - Ab interno pulsed dye laser sclerostomy uses a gonioscopic approach to form a limbal fistula for the treatment of glaucoma. This procedure requires a full thickness penetration of stain in sclera for adequate absorption of the visible light energy. Iontophoresis is a technique using an electrical current to noninvasively deliver Reactive Black 5 (RB5) stain into sclera. This project determined the stability of RB5 stain as well as the optimal parameters for iontophoresis (probe tip surface area, current, and duration) in a rabbit model. RB5 stain was stable over time (72 hr) as well as after exposure to extreme heat (120 degrees C), scleral constituents (namely collagen), high concentrations of oxidants (1.5% H2O2), and laser light energy. Ideal parameters for iontophoresis included a probe tip surface area between 0.1 and 0.7 mm2, a current of 0.5 mA, and a duration of 5 min. The maximum concentration of RB5 stain achieved in sclera was 0.15%. The threshold of ablation for RB5 using an energy of 250 mJ was 0.001%. Iontophoresis can effectively deliver RB5 stain into sclera and may be a viable adjunct to ab interno pulsed dye laser sclerostomy procedures in the eye. PMID- 8463731 TI - Identification of high intraocular pressure responders to topical ophthalmic corticosteroids. AB - To locate suitable candidates to study the intraocular pressure (IOP) effects of new ocular steroids, healthy volunteers must be challenged with topically applied steroids to verify that such individuals are indeed high "steroid responders"; that is, they respond with IOP elevations of at least 5 mmHg during a 4- to 6 week challenge with the topically applied steroid. We used first-degree offspring of individuals with primary open-angle glaucoma to develop a model to identify high steroid responders to topical ophthalmic prednisolone. We conducted a prospective, randomized, open-label, placebo-controlled study of prednisolone phosphate 1.0% in which 13 subjects received either topical prednisolone phosphate 4 times daily to the right eye and placebo to the left eye, or vice versa. Baseline evaluations occurred on study Day 0, and follow-up examinations were on Days 7, 14, 21, 28, 35, and 42. The medications were administered continuously for 6 weeks or until the IOP rose > or = 10 mmHg. After the effect of diurnal variation in IOP was taken into account, 4 of the 13 subjects (31%) had a maximum elevation in IOP of 4 mmHg or less, 7 subjects (54%) showed maximum elevations in IOP of 5 to 9 mmHg, and 2 subjects (15%) had a maximum IOP elevation of > or = 10 mmHg. Thus, a cumulative total of 9 subjects (69%) had IOP elevations of at least 5 mmHg and could be classified as moderate to high steroid responders. This model should become useful as a productive source of subjects for studies evaluating the effect on IOP of new ocular steroids. PMID- 8463732 TI - Formulation influence on ocular and systemic absorption of topically applied atenolol in the pigmented rabbit. AB - The objective of this study was to determine the relative efficacy of various formulations in maximizing the ratio of ocular to systemic absorption of topically applied atenolol following solution instillation in the pigmented rabbit. Formulations of various pH's and tonicities and containing various preservatives and polymers were tested. Ocular absorption was determined by monitoring atenolol concentrations in various anterior segment tissues at 30 min following solution instillation, while systemic absorption was determined by monitoring the time course of atenolol concentration over 480 min. Reversed phase HPLC was the analytical methodology. All formulations except those containing 0.025% benzalkonium chloride or 0.5% EDTA showed similar drug concentration vs. time profiles in plasma, attaining a peak concentration of 30-50 ng/ml at about 100 min. For benzalkonium chloride and EDTA, there was an undesirable increase in systemic absorption, although ocular absorption was also increased. By contrast, lowering the solution tonicity to 80 mOsm/kg increased the ratio of aqueous humor to plasma peak concentrations 2 times and the ratio of iris-ciliary body to plasma peak concentrations 3 times. Incorporation of 3.75% poly(vinyl alcohol) into the formulation afforded yet a larger increase in the iris-ciliary body to plasma drug concentration ratio (52 times.) It may therefore be concluded that, for a hydrophilic drug like atenolol, formulation changes that increase membrane permeability and/or enhance noncorneal drug access may be more promising than those that increase drug residence in the conjunctival sac with respect to maximizing the ratio of ocular to systemic drug absorption. PMID- 8463733 TI - Effect of ascorbic acid 2-0-alpha-glucoside on hydrocortisone-induced cataract formation in developing chick embryos: I. Comparison of the preventive effect of ascorbic acid derivatives. AB - The effect of ascorbic acid 2-O-alpha-glucoside (AA-2G) on hydrocortisone (HC) induced lens opacity in developing chick embryo was examined and compared with those of ascorbic acid (AsA) and ascorbic acid 2-phosphate (AA-2P). The opacity was dose-dependently inhibited by a single administration of 10 or 20 mumol/egg of AA-2G and by three repeated administrations of 1, 3 or 10 mumol/egg of AA-2G. AA-2G was the most effective among the three compounds. Glucose did not enhance the preventive effect of AsA against HC-induced opacity, and neither dehydro ascorbic acid nor glucose also prevented HC-induced cataract. In the histological study, we observed many small vacuoles in the nuclear region of the opaque lens treated with HC. AA-2G inhibited the formation of such vacuoles, an effect closely correlated with the prevention of cataract formation. PMID- 8463734 TI - Toxicity and pharmacokinetics of ciprofloxacin. AB - Ciprofloxacin is a fluorinated quinolone antibiotic with a broad spectrum of activity against both gram positive and gram negative organisms. Previous studies have indicated that oral or parenteral preparations of ciprofloxacin resulted in therapeutic concentrations in the aqueous humor but intravitreal levels were found to be only marginally higher than the MIC90 for gram positive cocci. Toxicity was evaluated following intravitreal doses of ciprofloxacin injected into the mid-vitreous cavity of one eye of pigmented rabbits. As a control, an identical volume of normal saline was injected into the fellow eye. Four doses of ciprofloxacin were studied, 100 micrograms, 250 micrograms, 500 micrograms and 1000 micrograms. Electroretinograms (ERGs) were recorded prior to injection and 1, 7 and 14 days after injection. These were analyzed as b-wave amplitude ratios between treated and untreated eyes. On ophthalmoscopic examination focal areas of retinitis were observed following injection of both 500 micrograms and 1000 micrograms of ciprofloxacin but not at 250 micrograms. Additionally, ERG amplitude ratios were significantly reduced following the 1000 micrograms dose. At the 100 or 250 micrograms ciprofloxacin dose histological sections are comparable with control eyes and appear normal; ERG ratios were unchanged from the baseline level and careful indirect ophthalmoscopic examination revealed no alterations. Pharmacokinetic analysis after single intravitreal injection of 250 micrograms of ciprofloxacin (N = 3 rabbits/dose) disclosed vitreous fluid levels (microgram/ml) of 146 at 0 hr, 77 at 4 hr, 32 at 8 hr, 0.49 at 24 hr and 0.24 at 48 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463735 TI - Vascular effects of calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in the monkey eye. AB - The effects of cholecystokinin (CCK) and calcitonin gene-related peptide (CGRP) on ocular blood flow were studied in monkeys using the labelled microsphere method. Intracameral administration of 800 pmole CGRP increased the blood flow significantly in the conjunctiva, ciliary body and sclera. There was no significant change in the choroid and retina. CCK-33 (800 pmole) caused no significant effects on the blood flow in the tissues examined, when compared to the control eyes. A miotic response was however noted, consistent with previous results. Neither peptide caused significant changes in the intraocular pressure. These results suggest that CGRP has a vasodilatory effect in some parts of the monkey eye, whereas CCK-33 is a miotic with no marked effect on ocular blood flow. PMID- 8463736 TI - Chronic systemic delivery of insulin through the ocular route. AB - Eyedrops of 0.25% insulin plus 0.5% BL-9 or Brij-78 were instilled into rabbit eyes twice a day for 3 months. It was found that the efficacy of insulin to lower the blood glucose concentration and the uptake of insulin into the systemic circulation remained the same throughout the experimental period. No allergic responses or local side effects could be detected, indicating that both insulin and permeation enhancers (BL-9 and Brij-78) are safe for instillation into the eyes for long periods of time. It is concluded that chronic administration of insulin and absorption enhancers into the eyes is a feasible method to replace injections for diabetes treatment. PMID- 8463737 TI - Bronchogenic carcinoma in young adults. AB - Lung cancer occurs most frequently in the sixth decade of life. It has been suggested that the incidence of bronchogenic neoplasm is increasing in the population under the age of 40. While this observation may simply reflect the general increase in lung cancer in both sexes, there is a distinct difference in the pathology and behavior of lung tumors that occur in the young. PMID- 8463739 TI - Cholera revisited. PMID- 8463738 TI - Preventive medicine: what do future practitioners really need? Are they getting it in medical school? AB - The purposes of our study were (1) to determine preventive medicine topics most relevant to clinical practice, and (2) to determine if medical education affects medical students' attitudes regarding preventive medicine. Our method of study was two surveys. The first survey asked practicing physicians to rank the 23 topics identified in the Healthy People 2000 monograph and determine their usefulness in clinical practice. The second survey assessed medical students' attitudes about preventive medicine. Practitioners ranked tobacco, cancer, and diabetes as most relevant to the actual clinical practice of medicine. There were no correlations between practitioners' gender, age, or region and their rankings of topics. In terms of specialties, surgeons felt preventive medicine was less important than did family practitioners. Medical students' attitudes about preventive practices became significantly more positive as they progressed through medical school. Survey scores also improved significantly in second year students after their preventive medicine course. Students planning to be surgeons were less positive about preventive medicine. There is a continuing need for prevention education in medical school curricula, especially about tobacco, cancer, diabetes, and nutrition. Epidemiology and disease reporting might best be presented as "how to read the literature." PMID- 8463740 TI - Health care reform. PMID- 8463741 TI - Cognitive development and learning in the pediatric organ transplant recipient. AB - Although organ transplantation is considered a viable treatment approach for end stage organ disease, few empirical investigations have assessed the effects of transplantation on the cognitive development and learning of pediatric organ transplant recipients. This article reviews studies evaluating neurocognitive changes following organ transplantation in pediatric end-stage renal and liver disease. Despite numerous methodological problems inherent in the investigations examined, the findings of some studies are suggestive of potential neurocognitive benefits associated with organ transplantation. Recommendations are made regarding methodological improvements for future investigations assessing neurocognitive outcomes of organ transplantation. PMID- 8463742 TI - School reentry for the child with chronic illness. AB - Chronic illness affects up to 20% of children in the school-age population, 10% of whom are severely compromised. Reintegrating these children is a growing problem for schools, children and their families, and health care professionals, as it has become apparent that school adjustment is highly significant in the children's overall adjustment. This article focuses on the issues of reintegrating the chronically ill child into the school setting, the types of school problems encountered, the process of school reentry, with illustrative case material, and the implications for the school and family of returning the chronically ill child to school. PMID- 8463743 TI - Traditional IQ is irrelevant to learning disabilities--intelligence is not. AB - This investigation examined the relationship between intelligence and phonological coding when ability was redefined according to the Planning, Attention, Simultaneous, Successive (PASS) cognitive processing model. This study directly tested the hypothesis that traditional IQ tests may be irrelevant to the definition of learning disabilities, but a different theory of intelligence may be more sensitive to deficiencies related to reading failure. Normally achieving students (n = 30) and students with reading disabilities (n = 30) ranging in age from 7.7 years to 15.3 years (mean = 11.9 years, SD = 2.4 years) were administered measures of the PASS cognitive processes, the Woodcock-Johnson Psycho-Educational Battery-Revised pseudoword reading, and the Wide Range Achievement Test-Revised (WRAT-R) reading recognition tests. Results showed that the sample with reading disabilities earned significantly lower scores on the WRAT-R Reading (mean = 69.3) than the nondisabled subjects (mean = 91.4) and, similarly, on pseudowords those with reading problems earned a mean of 78.9 while the nondisabled earned a mean of 96.3. For the sample with reading disabilities, pseudoword reading scores were significantly predicted by successive processing scores (R2 = .267), but no other processing variable added to the prediction; successive scores (R2 = .212) and the combination of successive and planning (R2 = .296) were significant predictors of WRAT-R Reading scores. PMID- 8463744 TI - Assessment of oral storytelling abilities of Latino junior high school students with learning handicaps. AB - This study investigated the relationship between reading comprehension and oral storytelling abilities. Thirty-one Latino junior high school students with learning handicaps were selected as subjects based on learning handicapped designation, home language, and language proficiency status. Reading comprehension was measured by the Reading Comprehension subtest of the Peabody Individual Achievement Test. Storytelling was measured by (a) the Oral Production subtest of the Language Assessment Scales using the standard scoring protocol and (b) a story structure analysis. A comparison of the standard scoring protocol and reading comprehension revealed no relationship, while the comparison of the story structure analysis and reading comprehension revealed a significant correlation. The implications of these results for language assessment of bilingual students are discussed. PMID- 8463746 TI - A look at the relationships of parties involved in medical malpractice litigation with a view toward helping the patient. PMID- 8463745 TI - Cognitive, neuropsychological, and academic sequelae in children with leukemia. AB - The literature concerning the cognitive and neuropsychological sequelae of children in whom leukemia has been diagnosed indicates that these children exhibit deficits in cognitive and neuropsychological functioning and academic achievement in response to the iatrogenic effects of central nervous system (CNS) irradiation. Preliminary studies suggest that similar emanative effects may follow intrathecal chemotherapy, an alternative to CNS irradiation for children given a favorable prognosis. It is concluded that treatment advances have lengthened the life expectancy of many children with leukemia, thereby changing their prognosis to a more favorable one. This has resulted in a recognition of the difficulties accompanying school reentry. In light of their documented neuropsychological, academic, and social adjustment problems, many of these children require special education services. PMID- 8463747 TI - Options at the end of life. PMID- 8463748 TI - Elements of causation in toxic tort litigation. Science and law must agree. PMID- 8463749 TI - Regulation of experimentation on the unborn. PMID- 8463750 TI - Abortion law today. PMID- 8463751 TI - Maternal substance abuse during pregnancy. Policy implications in the United States. PMID- 8463752 TI - Maternal-fetal relationship. The courts and social policy. PMID- 8463753 TI - Forcing the issue of physician-assisted suicide. Impact of the Kevorkian case on the euthanasia debate. PMID- 8463754 TI - Medicine, 2003. PMID- 8463755 TI - Self-referral legislation for Georgia? PMID- 8463756 TI - Economic credentialing revisited: watch out, here it comes! PMID- 8463757 TI - Ambitious agenda for the 1993 Georgia General Assembly. PMID- 8463758 TI - Cancer trends unique to Georgia. AB - Using information from 1980 through 1991 Cancer Statistics, published by the American Cancer Society, we assigned a rank order of new cancer cases for Georgia and eight other states. Female breast, colon and rectum, lung, oral, uterus, prostate, pancreas, and leukemia are the site-specific cancers that were considered. There was an increasing trend in Georgia for colon and rectal cancer and breast cancer during this study period. This increased trend for colorectal and breast cancer in Georgia was not apparent in the other index states. Possible influences of population, physician practices, and socioeconomic factors are considered. The results of this project indicate that further study is needed to evaluate this trend, possibly by examination of regional differences within the state of Georgia, especially with regard to environmental factors. PMID- 8463759 TI - Annotated guidelines on gifts to physicians from industry. AMA Council on Ethical and Judicial Affairs. PMID- 8463760 TI - Flying doctors. PMID- 8463761 TI - Nicotine dependence--treatment for the 1990s. AB - Physicians must recognize that nicotine is a powerfully addictive drug, and patients with nicotine dependence will have all the hallmarks of an addictive disorder. To successfully treat such patients will require compassion and patience on the part of the physician along with the realization that successful treatment will not be easy for most. As with other drugs, there is a very high relapse rate after initial abstinence and this can be discouraging for physicians and patients alike. Applying the principles outlined above in a stepped-care fashion will lead to greater success in dealing with this difficult problem. In the future, more effective treatment interventions will be developed and tested but it is unlikely that there will be a simple cure for this complex behaviour which is complicated by a powerfully addictive drug. Though not a cure-all, adjunctive pharmacologic therapy will play an increasingly important role as we learn how to better use existing agents and as others are shown to be effective. The key to the future is in the development of better relapse prevention techniques to enhance the rather remarkable short-term success rates that can be achieved with counselling and adjunctive pharmacologic therapy. PMID- 8463762 TI - Bone marrow transplantation in Europe--can the geographical differences be explained? PMID- 8463763 TI - The clinical importance of silent ischaemia during exercise--new insights in different stages of coronary artery disease. PMID- 8463764 TI - Diabetes education and insulin therapy: when will they ever learn? AB - The Diabetes Education Study Group of the European Diabetes Association was founded in 1979 with its major goal to make effective patient training an integral part of any diabetes therapy. However, even today, in many places diabetes education is not an obligatory part of treatment, but is regarded as an optional service to the patient which is frequently fragmentary and haphazard. On the other hand, many physicians still subject their patients to rigid dietary instructions and obedience training, an approach which is mistaken for diabetes education. Several misconceptions about diabetes education keep counteracting the spread and hence the availability of effective treatment and teaching programmes for all Type 1 diabetic patients. One such misconception is that diabetes education could compensate for deficiencies of inappropriate insulin treatment regimens. Studies failing to demonstrate the impact of diabetes education on metabolic control, typically used an insulin treatment regimen with only one or two insulin injections per day, the predominant use of intermediate acting insulin preparations, and without (day-to-day) adjustment of insulin dosages by the patients themselves. A further reason for a lack of success of diabetes education is an unstructured approach which is frequently mistaken for individualized care. The deleterious effects of putting patients on intensified insulin therapy without offering them sufficient and systematic training have manifested themselves at various places by an excessive increase in the risk of severe hypoglycaemia, and of ketoacidosis during therapy with continuous subcutaneous insulin infusion. The effective and safe performance of insulin therapy requires both a rational system of insulin substitution and intensive training of the patients to carry it out. The injection of regular insulin before main meals and the use of intermediate or long-acting insulin preparations for the substitution of basal insulin requirements combined with daily metabolic self monitoring and (day-to-day) adaptation of insulin dosages by the patients themselves allow a substantial improvement of glycaemic control without an increase in the risk of severe hypoglycaemia and the adoption of a more flexible life style largely freed from forcing and directive dietary and other impositions. Each diabetes centre should continuously evaluate the quality of care offered to their patients as a basis for a specific and systematic improvement of its treatment and education programmes. Such quality control measures must include a recording of the patients' degree of metabolic control and the frequencies of severe hypoglycaemia and ketoacidosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463765 TI - Smoking induces insulin resistance--a potential link with the insulin resistance syndrome. AB - OBJECTIVES: The acute effect of smoking and snuffing on insulin sensitivity was studied in a group of healthy habitual smokers. DESIGN: The euglycaemic clamp technique was combined with the subcutaneous injection of a bolus (0.1 U kg-1) of fast-acting insulin (Actrapid). Randomized subjects smoked either one cigarette per hour for 6 h, took one bag-packed snuff per hour for 6 h or refrained from nicotine for 48 h before as well as during the clamp. SUBJECTS: Seven healthy smokers, four females and three males, of normal weight (BMI, mean +/- SEM, 21 +/ 0.7 kg m-2 with a range of 18.6-23.9), aged 31 +/- 2 years (range 24-35 years), who had consumed at least 20 cigarettes per day for at least 5 years were studied. They were recruited through an advertisement in a newspaper. RESULTS: The steady-state plasma nicotine levels were similar during smoking and snuffing. The insulin and glucose levels were also similar during all three clamps. Smoking, but not snuffing, impaired insulin action (P < 0.05) mainly due to a lower peripheral glucose uptake. The mean growth hormone levels during the 6-h study were more than doubled during smoking (P < 0.01) while no significant differences were seen in the other counter-regulatory hormones. CONCLUSION: Smoking (also in habitual smokers) acutely impairs insulin action and leads to insulin resistance. Thus, smoking can be of importance for the development of the insulin resistance syndrome associated with risk for cardiovascular disease. PMID- 8463766 TI - Bone marrow transplantation in Europe: major geographical differences. The European Group for Bone Marrow Transplantation [EBMT]. AB - In 1991 171 teams in 21 European countries performed 4976 bone marrow transplants. There were 1829 transplants from an HLA-identical sibling donor, 101 from a nonidentical family member, 30 from a twin, 217 from an unrelated volunteer donor and 2799 autologous transplants. Indications for transplants were leukaemias in 2569 (52%), lymphoproliferative disorders in 1472 (30%), solid tumours in 549 (11%), aplastic anaemia and thalassaemia in 261 (5%), inborn errors in 97 and miscellaneous disorders in 28 patients. There are marked differences between the participating European countries. They relate to absolute numbers, indications and techniques. Less than 10 transplants per 10-million inhabitants are performed in Eastern European countries. Ten to fifty transplants per 10-million inhabitants are done in two, 50-100 transplants per 10-million inhabitants in five, 100-200 transplants per 10-million inhabitants in eight countries and more than 200 per 10-million inhabitants in one country (P < 0.01). The number of transplant teams ranges from less than one to twelve per 10-million inhabitants (P < 0.01). For the continent it becomes 3.3 per 10-million inhabitants. The reasons for these differences are not explained by this survey. The most likely explanation for the differences in transplant activity is availability of transplant beds, trained staff and resources. Bone marrow transplants are expensive. However, the demand is increasing and will increase further with the routine availability of unrelated volunteer donors. Clearly, criteria are required in Europe to define the indications and solutions to meet the legitimate requirements for transplantation in the various regions of Europe. PMID- 8463767 TI - Accelerated coronary artery disease after heart transplantation: the role of enhanced platelet aggregation and thrombosis. AB - The present study is a prospective examination of the relationship between platelet aggregation and the occurrence of graft failure in a single cohort of heart transplantation (HT) recipients. One-hundred-and-twenty-four patients underwent platelet function study and were then followed for 1 to 24 months (mean 6.7 months). There were nine re-transplantations and 13 deaths (11 related to ischaemic events, and two others). In 15 patients, pathologic examination confirmed or revealed that recent acute myocardial infarction was the obvious cause of the graft failure. In five patients, myocardial fibrosis related to severe and diffuse coronary disease was the only microscopic finding. In the last two patients, the cause of the heart failure was not clearly identified. In recent myocardial infarction there was a high incidence (14/15) of coronary thrombi. Thrombi were multiple, disseminated in the coronary tree end of different age. Their presence at autopsy or after explantation was associated with an enhanced ex vivo platelet aggregability as compared with patients without coronary thrombi (n = 8): 43.3 +/- 1.7% of maximal aggregation vs. 34.4 +/- 2.4 (P = 0.006) and 48.4 +/- 5.2 vs. 22.6 +/- 4.9 (P = 0.003) for the primary and secondary waves of ADP-induced aggregation. These results suggest that thrombosis and platelets may play a major role in the process of accelerated coronary artery disease after HT. PMID- 8463768 TI - Effect of coffee on ambulatory blood pressure in patients with treated hypertension. AB - Effects of caffeine on ambulatory blood pressure, heart rate, renin-angiotensin system, and ANP were studied in patients treated for mild to moderate hypertension in a randomized, double-blind, placebo-controlled, cross-over trial comparing 2 weeks of caffeine-free diet with 2 weeks of regular coffee use. Twenty-three patients (13 men; aged 28-74 years) with treated, mild to moderate essential hypertension and a regular intake of 3-4 cups of coffee daily completed the study. Mean 24-h, day- or night-time ambulatory blood pressure and heart rate were not different between regimens. Nor were there any effects on the renin angiotensin system while ANP was significantly increased during caffeine intake. Compliance of the dietary regimen was excellent as assessed by serum caffeine concentration measurements. We conclude that habitual coffee drinking did not influence the 24-h blood pressure profiles or cardiovascular hormones in treated hypertensives. PMID- 8463769 TI - Low blood pressure and blood glucose levels in Alzheimer's disease. Evidence for a hypometabolic disorder? AB - OBJECTIVE: To test possible differences between patients with Alzheimer's disease (AD) and patients with other forms of dementia and the healthy population concerning body composition, blood pressure, metabolic data and leukoaraiosis (LA). DESIGN: Retrospective study on data collected according to a predefined protocol. SETTING: A geriatric, neuropsychiatric diagnostic unit. SUBJECTS: Seventy-one consecutive patients with dementia. MAIN OUTCOME MEASURES: Body mass index, blood pressure, metabolism and LA in AD compared to other dementia forms. RESULTS: Mean blood pressure and fasting blood glucose levels were lower in patients with AD, 94 +/- 12 mmHg and 4.3 +/- 0.5 mmol l-1, compared to patients with unspecified dementia (NUD), 100 +/- 10 mmHg and 5.5 +/- 2.5 mmol l-1 (P < 0.05) and vascular dementia (VAD), 114 +/- 12 mmHg and 5.6 +/- 1.6 mmol l-1 (P < 0.001) and the age-matched healthy population. Body mass index, serum cholesterol and cortisol were similar in all groups of dementia patients whereas triglycerides were highest in the VAD group. No cases of diabetes or treatment for hypertension were found in the AD group while the prevalence was 21% and 36% for diabetes in the NUD and VAD groups and 8% in the population from the same region. There were 16% with antihypertensive treatment in dementia NUD, 50% in VAD, and 30% in the general population. Treated or newly detected hypothyreosis was present in 11% of the AD patients, none in the other dementia groups and 2% in the general population. Smoking was least common in AD. Degree of LA correlated with blood pressure and blood glucose levels. CONCLUSIONS: AD was clearly different to other dementia patients. They had lower blood pressure, blood glucose and higher prevalence of hypothyreosis than the healthy, age matched population. These findings may indicate that AD could be a hypometabolic disorder. PMID- 8463770 TI - Renal failure due to sulphadiazine in AIDS patients with cerebral toxoplasmosis. AB - Cerebral toxoplasmosis is optimally treated with the combination of high doses of sulphadiazine and pyrimethamine. We described two patients with AIDS treated for cerebral toxoplasmosis who developed renal failure due to sulphadiazine-induced crystalluria. Symptoms and renal failure were rapidly reversed with urine alkalinization and hydration. A careful monitoring and adequate hydration of patients with AIDS treated with high doses of sulphadiazine appears mandatory to avoid this complication. PMID- 8463771 TI - Vitamin B12 deficiency. PMID- 8463772 TI - Vitamin B12 deficiency. PMID- 8463773 TI - Vitamin B12 deficiency. PMID- 8463774 TI - Human genome. PMID- 8463775 TI - Patient-physician relationship. PMID- 8463776 TI - Chiropractic. PMID- 8463777 TI - Chiropractic. PMID- 8463778 TI - Obtaining informed consent: it is not simply asking "do you understand?". PMID- 8463779 TI - Informed consent: who's informed? Who's consenting? And other questions. PMID- 8463780 TI - Differences in management of suspected myocardial infarction in men and women. AB - BACKGROUND: Men and women with ischemic heart disease receive different medical treatment. Men receive more aggressive intervention and at an earlier stage of disease. However, differences in treatment between sexes have thus far been demonstrated only for invasive treatment, which may be less effective for women than for men. METHODS: In a small community hospital, all patients admitted to the family practice service for suspected acute myocardial infarction from July 1988 to June 1989 were evaluated retrospectively to determine the reasons for placement in the cardiac care unit (CCU) vs regular nursing bed units with telemetry. The variables considered were patient age, patient sex, physician sex, and the likelihood of ischemia based on the Acute Ischemic Heart Disease Predictive Instrument (HDPI). RESULTS: Ninety-three patients were entered in the study. The patient's age, sex, and likelihood of ischemia as measured by HDPI score were significantly related to probability of placement in the CCU. Women were less likely than men to be placed in the CCU, controlling for age and likelihood of ischemia (OR = 0.362, 95% CI = 0.135 to 0.977). CONCLUSIONS: Women appear to receive not only less intensive invasive treatment for ischemic heart disease than men, as previous studies have shown, but also less aggressive noninvasive treatment. This may represent unnecessary treatment of men rather than undertreatment of women. The findings of this study suggest, however, that physicians view women presenting with suspected acute myocardial infarction with less urgency than men presenting with similar symptoms. PMID- 8463781 TI - Sedation associated with a more complete colonoscopy. AB - BACKGROUND: This study examined the effect of sedation on the rate of complete colonoscopic examinations by a family physician performing colonoscopy at an urban family practice residency. The outcomes of biopsies and polypectomies performed during the period of the study were also evaluated. METHODS: Data were prospectively collected on 164 consecutive colonoscopies. Seventy-three percent (124/164) of the examinations were training experiences supervised by the first author. The outcomes of examinations of 126 sedated patients were compared with those of 38 nonsedated patients. Patients were not randomly selected. RESULTS: Examinations of 126 sedated patients were carried out with an 85% reach-the-cecum rate compared with a 31% reach-the-cecum rate for 38 nonsedated patients (P < .05). A higher percentage of examinations done without sedation (16%) were terminated because of pain than were terminated in sedated patients (5%) (P < .05). An electrolyte purge solution was found to be the most effective colonoscopy preparation; only 7% (7/100) of examinations on patients prepared by this method were terminated because of inadequate bowel preparation. Adenomas were found in 11% (14/126) of sedated patients and in 8% (3/38) of nonsedated patients. Cancer was detected in 4 sedated patients. CONCLUSIONS: These findings suggest that sedation in colonoscopy is associated with a higher percentage of complete examinations. Also, patients prepared with an electrolyte purge solution tend to have fewer examinations terminated because of inadequate preparation. PMID- 8463782 TI - Diet and exercise and gemfibrozil therapy for the management of dyslipidemia: a CEN study. Clinical Experience Network. AB - BACKGROUND: Dyslipidemia constitutes a serious health problem that should be diagnosed and treated by the family physician. Little is known about the efficacy of typical dietary therapy for patients with abnormal cholesterol levels. This study was the first large prospective family practice evaluation of the effectiveness of diet-and-exercise therapy followed by a pharmacologic intervention for those patients who remained dyslipidemic. METHODS: Patients who met standard criteria for cardiovascular disease risk based on lipid analysis were enrolled in a typical 6-week physician-directed diet-and-exercise program. Those patients who were still dyslipidemic after that period were started on 12 weeks of pharmacologic treatment with gemfibrozil. RESULTS: Of the 2992 patients screened, 1193 were eligible for participation in the study. The diet-and exercise program led to a modest change in lipid values (average decrease in total cholesterol of 4.1%). Only 2% of the patients achieved desirable levels of all lipid values. Seven hundred thirty-nine subjects qualified for further therapy and were treated with gemfibrozil. Seventy patients discontinued drug therapy because of adverse effects. Those who completed 12 weeks of pharmacologic therapy had an additional 5.4% reduction in total cholesterol, 3.9% reduction in low-density lipoprotein cholesterol, 30.6% reduction in triglycerides, and a 17.2% increase in high-density lipoprotein cholesterol. CONCLUSIONS: These findings suggest that in a typical clinical setting, a nonpharmacologic intervention of diet and exercise may not produce the desired overall lipid changes in the majority of dyslipidemic patients. PMID- 8463783 TI - Obtaining a durable power of attorney for health care from nursing home residents. AB - BACKGROUND: A durable power of attorney for health care (DPA) allows a person to appoint a surrogate decision-maker for any future period of mental incapacity. The absence of advance directives can lead to confusion and the expenditure of resources while trying to exert a substituted judgment. METHODS: The Wisconsin DPA was presented with an organized pilot program to 150 residents who had been judged by their social workers to have the capacity to make informed decisions regarding medical care. The reasons residents gave for accepting or rejecting a DPA were analyzed. RESULTS: Seventy-nine percent prepared a DPA. Reasons for signing included allowing the resident to decide who would make medical decisions and assuring that specific wishes would be carried out. Twenty-one percent did not execute a DPA. Reasons were categorized as confusion and misunderstanding regarding the legal system, mistrust, or social isolation. CONCLUSIONS: The high rate (79%) of DPA completion is probably related to individually counseling residents. However, competent residents who despite counseling do not choose to execute a DPA can have detailed advance directives ("living wills") prepared without appointing a decision-maker. PMID- 8463784 TI - Physician views on frequent medical use: patient beliefs and demographic and diagnostic correlates. AB - BACKGROUND: Health care "misusers" have long been identified as hypochondriacs, problem patients, "worried well" patients, and persistent somatizers. The stereotypical pattern includes persistent pursuit of medical care, a wide range of chronic symptoms, and underlying depression. The purpose of this study was to gather prevalence data on individual patients and to examine patient variables that influence the use of medical services by this population. METHODS: Frequent health care users in an HMO were classified by their primary care providers in terms of appropriate use (36%), moderate misuse (inappropriate or psychosomatic, 27%), and extreme misuse (both inappropriate and psychosomatic, 37%) categories. Utilization and diagnostic data were compared using analysis of variance or chi square tests. RESULTS: All patients rated as misusers to any degree represented only 17.1% of the population, yet accounted for 42.7% of the visits. Extreme misusers accounted for 25% of visits and 10% of the population. Compared with frequent appropriate users, misusers had a greater belief in their own responsibility for health (internal health locus of control), expressed more concern about their mental health, and rated psychological symptoms as more serious. In addition, extreme misusers were younger, reported more symptoms, and believed less in the physician's control of their health. Misusers sought care for minor symptoms or for complaints that were not diagnosed as disease. CONCLUSIONS: Misuse as a physician-perceived variable is highly prevalent. Misusers differ in their beliefs about health care as well as in the kinds and severity of problems for which care is sought. Physicians need to be sensitive to the interpersonal nature of this problem so as not to discourage preventive medical use, and to recognize the value of these visits to the "worried well" population. PMID- 8463785 TI - Racial differentials in the identification of hypercholesterolemia. AB - BACKGROUND: African Americans have higher rates of cardiovascular disease than white Americans. To address this differential, barriers to cardiovascular risk reduction need to be identified. This study examines the association of race with the likelihood of screening for and diagnosis of hypercholesterolemia. METHODS: Possible associations between demographic variables and screening for and diagnosis of hypercholesterolemia were examined on data gathered in a prospective fashion in an office-based family medicine residency training program in Rochester, New York. A consecutive sample of all patients seen between December 15, 1988, and April 15, 1990, about whom there was complete data collection (age, sex, insurance, race, and other cardiovascular risk factors) were included in the multivariate analyses (N = 4256). RESULTS: After controlling for age, sex, insurance status, socioeconomic status, number of visits, and other cardiovascular risk factors, it was found that minorities were less likely to have been screened for cholesterol levels than whites (adjusted odds ratio [AOR] = 0.84, 95% confidence interval [CI] = 0.98 to 0.72). The mean cholesterol level did not differ by race (mean cholesterol for whites, 204 mg/dL [5.28 mmol/L], and for minorities, 203 mg/dL [5.25 mmol/L], t = 0.7, P = .47). Among those screened, minorities were less likely than whites to have been diagnosed with hypercholesterolemia (AOR = 0.62, 95% CI = 0.86 to 0.44; and 0.47 (95% CI = 0.28 to 0.78] in those with a cholesterol level greater than 240 mg/dL [6.2 mmol/L]). CONCLUSIONS: Our data suggest that provider behavior in diagnosing hypercholesterolemia varies by the race of the patient. PMID- 8463786 TI - Nursing home care in 2001. AB - As we move toward the 21st century, nursing home care will become an increasingly important part of family practice. The number of nursing home residents will grow, their illnesses will become more acute, and the types of medical services provided by nursing homes will broaden. The fiscal difficulty of providing nursing home care will intensify, and a variety of innovative payment programs will be introduced in an attempt to control costs. The only way these will succeed is by a partial reallocation of health care dollars from expensive high technology hospital care to less expensive low-technology care in nursing homes. As a result of these changes, hospitals will become more involved in the provision of what were traditionally nursing home services. Nursing homes will be used to a larger extent for medical education, and, under congressional pressure, a shrinking pool of federal research dollars will be more fairly allocated to clinical investigation in this setting. PMID- 8463787 TI - Parkinson's disease: early diagnosis and management. AB - Parkinson's disease is a common neurodegenerative disorder affecting approximately 1% of the population over the age of 50 years. There is no known cure for Parkinson's disease, but research gains over the last two decades have been substantial, resulting in improved medications and therapeutic strategies for managing early symptoms and delaying the onset of serious disability. Particularly promising is current research suggesting the possibility of neuroprotective therapies that may ultimately be capable of slowing disease progression. Early and accurate diagnosis is especially important to optimize the benefits of new therapies. PMID- 8463788 TI - Postpartum pyometra: a case report. AB - Pyometra is an uncommon result of endometritis. The diagnosis of pyometra is made when a collection of pus is found within the endometrial cavity. Antibiotic administration and drainage of the pus are essential to resolve this condition. A report of a case of pyometra is presented and a technique for drainage is described. This case demonstrates the use of office-based diagnostic ultrasonography to narrow the differential diagnosis and guide the drainage procedure, as well as the use of simple ingenuity to improve patient care. PMID- 8463789 TI - Mesenteric venous thrombosis: a case report. AB - Mesenteric venous thrombosis is an uncommon entity. The preoperative diagnosis is largely clinical; the hallmark is pain that is out of proportion to the physical findings. Treatment consists of thrombectomy with resection of necrotic small bowel and mesentery. In the absence of trauma or infection, an investigation of intrinsic anticoagulant deficiencies is warranted since these deficiencies are inherited in an autosomal dominant fashion. Treatment is warfarin sodium therapy. PMID- 8463790 TI - Beauty and the beast: do you really know your patient's family? PMID- 8463791 TI - The role of organic osmolytes in osmoregulation: from bacteria to mammals. AB - Cells of marine species are known to establish osmotic balance with their environment by adjusting the concentrations of organic osmolytes rather than inorganic osmolytes such as sodium, potassium, and chloride. These organic osmolytes fall into three classes: polyhydric alcohols such as sorbitol, amino acids and amino acid derivatives, and urea and trimethylamines. Substantial evidence is available for a central role of each of these classes in osmoregulation in marine species. In this chapter information on the importance of organic osmolytes is extended to a study of isolated mammalian kidney cells. The intracellular concentration of organic osmolytes in these cells responds dramatically to changes in the osmotic environment. The release of sorbitol following hypoosmotic exposure appears to be triggered by calcium, possibly via a mechanism involving membrane recycling. The summarized experiments provide a basis for further work in marine species. PMID- 8463792 TI - Cold shock damage is due to lipid phase transitions in cell membranes: a demonstration using sperm as a model. AB - When cells are cooled to temperatures above the freezing point of water at rates greater than a few degrees per minute, they sustain irreversible injury. Reduction of this "cold shock" damage could increase the survival of animals and plants at low environmental temperatures and improve the cryopreservation of plant and animal cells. Leakage of solutes across membranes, associated with thermotropic phase transitions in membrane lipids, is thought to be responsible, but this hypothesis has not been tested directly. Using Fourier transform infrared spectroscopy (FTIR), we measured the lipid phase transitions in intact, living sperm, the animal cell in which cold shock has been studied most extensively. A shift in the CH2 absorbance peaks indicates the transition from liquid-crystalline to gel phase. The phase transition in sperm membranes occurred at a lower temperature for a marine shrimp than for the pig. In each case, potassium leakage, which is a hallmark of cold shock damage, increased abruptly near the end of the phase transition. Human sperm are quite resistant to cold shock, and an abrupt lipid phase transition was not detected. This phase behavior is typical of membranes containing a high proportion of cholesterol, and human sperm have an unusually high sterol content. High cholesterol levels are known to stabilize membranes during cooling. Overall, the lipid phase behavior was consistent with the temperature range over which cooling was damaging for pig and shrimp sperm, and the with the extent of damage produced in pig and human sperm. This is the first direct evidence that cold shock results from lipid phase transitions in cell membranes. PMID- 8463793 TI - Production of an anti-allergic triterpene bryonolic acid, by plant cell cultures. AB - Cell suspension cultures of Luffa cylindrica, Citrullus lanatus, and related cucurbitaceous plants accumulate large quantities of bryonolic acid (3 beta hydroxy-D:C-friedoolean-8-en-29-oic acid) [1], an acidic, pentacyclic triterpene found exclusively in the roots of the intact plants. This compound could readily be isolated from cultured cells with CHCl3 and purified simply by recrystallization. Pharmacological tests using mice demonstrated that bryonolic acid or its derivative is active against at least three types of allergies and that its activity could be increased significantly by preparing synthetic derivatives, in particular a potassium salt of its succinate ester. The biosynthesis of bryonolic acid from mevalonic acid via isomultiflorenol has been elucidated by tracer and enzymological experiments using cultured cells of watermelon both in vitro and in vivo. Furthermore, cell fractionation and electron microscopic studies on subcellular structures of luffa cells suggested that minute vesicles originating from elongated, rough endoplasmic reticulum probably play an important role in the transport of bryonolic acid which largely accumulates in the cell wall of cultured cells. The results obtained from the present study indicate that plant cell culture would be useful not only as a biological system for elucidating biosynthetic mechanisms but also as a potential source of new pharmacologically active compounds. PMID- 8463794 TI - Crystal structure of artemisinic acid: a possible biogenetic precursor of antimalarial artemisinin from Artemisia annua. AB - Artemisinic acid [1], a possible biogenetic precursor of the antimalarial artemisinin [2], was isolated from the hexane extract of Artemisia annua. X-ray crystallography of the dimer of artemisinic acid shows that the cyclization during intermolecular hydrogen bonding occurs by the opposite orientation of the alpha, beta-methylene group in each molecule. Complete spectroscopic data of 1 are also given. PMID- 8463795 TI - Combination effects of antifungal nagilactones against Candida albicans and two other fungi with phenylpropanoids. AB - Antifungal activity of three nagilactones isolated from the root bark of Podocarpus nagi (Podocarpaceae), alone and in combination with a variety of phenylpropanoids, was investigated against three fungi, Candida albicans, Saccharomyces cerevisiae, and Pityrosporum ovale. Nagilactone E [2], the most abundant norditerpene dilactone, showed moderate to weak activity against these fungi. This activity was dramatically enhanced by several naturally occurring phenylpropanoids such as anethole [5] and isosafrole. For example, anethole enhanced the activity of nagilactone E as much as 128-fold for C. albicans, decreasing the MIC of this nagilactone from 800 to 6.25 micrograms/ml. PMID- 8463796 TI - Triterpenoid saponins from Bupleurum fruticosum. AB - Three triterpenoid saponins 1-3 of the oleanane series, containing one fucose and two glucose units, were isolated from the MeOH extract of the roots of Bupleurum fruticosum. Their structures were elucidated by means of fabms and a combination of homo- and heteronuclear 2D nmr techniques. Two of the three saponins are new. PMID- 8463797 TI - Unprecedented oxylipins from the marine green alga Acrosiphonia coalita. AB - The Oregon marine chlorophyte Acrosiphonia coalita produces an assortment of oxidized polyunsaturated fatty acids, or oxylipins. The smallest of these was a 10-carbon conjugated trienal 1 with antimicrobial properties. Related to 1 were three novel branched-chain conjugated trienals 4, 5, and 9 in which the aldehyde was present as a branch on a 17-carbon fatty acid chain. Additionally, two novel conjugated unbranched trienone octadecanoids 8 and 10 were also isolated and characterized. Finally, a family of related epoxy-alcohols (11, 12, 15, and 17) was obtained from A. coalita. Structures were determined by spectroscopic methods in combination with formation of various degradation products and derivatives. The absolute stereochemistry of several of these metabolites was determined by application of exciton chirality circular dichroic spectroscopy on benzoate derivatives. PMID- 8463798 TI - Isolation and structure of the marine sponge cell growth inhibitory cyclic peptide phakellistatin 1. AB - A new cell growth inhibitory (P-388 murine leukemia ED50 7.5 micrograms/ml) cycloheptapeptide designated phakellistatin 1 was isolated from two Indo-Pacific sponges, Phakellia costata and Stylotella aurantium. Structural elucidation was accomplished utilizing high field nmr, amino acid analyses, and mass spectral techniques (fab, tandem ms/ms), followed by chiral gas chromatographic procedures for absolute configuration assignments (all S-amino acid units). By these methods phakellistatin 1 [1] was found to be cyclo (Pro-Ile-Pro-Ile-Phe-Pro-Tyr), and this assignment was finally confirmed by an X-ray crystal structure determination. PMID- 8463799 TI - Isolation and identification of an antifungal naphthopyran derivative from Rhinacanthus nasutus. AB - Rhinacanthus nasutus (Acanthaceae) gave a new antifungal naphthopyran derivative. The structure of the compound was elucidated by spectroscopic methods as 3,4 dihydro-3,3-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione [1]. PMID- 8463800 TI - Changes in renal vein, renal surface, and urine oxygen tension during hypoxia in pigs. AB - To determine whether ureteral urine oxygen tension could serve as a monitor of renal hypoxia and its relationship to other renal O2 tension parameters, we simultaneously measured femoral artery (PaO2), renal vein (PrvO2), renal surface (PrsO2), and ureteral urine (PuO2) oxygen tensions in 8 anesthetized pigs while incrementally decreasing the inspired oxygen concentration (FiO2) from 21% to 12%. Renal artery blood flow, measured by transit time ultrasound, renal oxygen consumption, and thermodilution cardiac output, was constant. Changes in PaO2, PrvO2, PrsO2, and PuO2 caused by decreasing FiO2 were evaluated by one-way analysis of variance. The relationships between PuO2 and the other O2 tension parameters were evaluated by correlation coefficient and linear regression statistics. Of six possible O2 decrements (combinations of 3, 6, and 9%), only PrvO2 significantly decreased with all six decrements. PuO2 decreased when FiO2 decreased 6% or more. PuO2 is not a sensitive indicator of systemic hypoxia. Under constant renal perfusion and oxygen consumption, PuO2 had a correlation coefficient of 0.80 and a regression equation of PuO2 = 0.84 (PrvO2) + 11.6, with PrvO2. PuO2 is related to PrvO2 when renal perfusion is constant. PMID- 8463801 TI - Noninvasive continuous blood pressure measurement: a clinical evaluation of the Cortronic APM 770. AB - The Cortronic APM 770 (Cortronic, Ronkonkoma, NY) is a commercial device that claims to measure blood pressure noninvasively and continuously with the use of a standard blood pressure cuff. The aim of our study was to assess the performance of the continuous-mode blood pressure readings of the Cortronic during anesthesia and surgery. We recorded blood pressure in 5 patients bilaterally. An interaarterial pressure (IAP) curve was recorded from 1 arm and the Cortronic pressure curve (CPC) was recorded from the other. For statistical analysis the period between 2 Cortronic recalibrations was defined as the intercalibration interval. The duration of these intervals ranged from 20 to 0.5 minutes. Four paired samples were drawn from each interval. The first sample in an interval represented the recalibration blood pressure; the other samples represented the continuous blood pressure. A total of 1,232 samples were taken, of which 308 were recalibration. The median of the differences and the 2.5th and 97.5th percentile limits of agreement were determined. Their respective values for diastolic and systolic recalibration measurements were 5, -17, and 34 mm Hg, and 6, -12, and 38 mm Hg. Their values for continuous measurements were 4, -23.5, and 32 mm Hg, and 6, -30, and 70 mm Hg. Changes in CPC were evaluated against changes in the corresponding IAP by plotting them in 4-quadrant graphs. In these graphs the Spearman rank correlations were between r = -0.17 and r = 0.01. We observed opposite CPC and IAP trends on 24 occasions during this study. We performed a simple simulation study to better understand the measurement method of the Cortronic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463802 TI - An adaptive controller for the administration of closed-circuit anesthesia during spontaneous and assisted ventilation. AB - Although reduced waste of expensive anesthetic gases is a strong incentive to use closed-circuit anesthesia, manual methods of performing closed-circuit anesthesia are labor intensive and thus not widely used. Automation of closed-circuit anesthesia delivery may reduce the work. A pressure-based adaptive controller was designed and tested on mongrel dogs to evaluate the feasibility of automating closed-circuit anesthesia using an accessory to an existing clinical anesthesia machine and a gas analyzer. The controller was found stable and responsive with good control of oxygen concentration and acceptable control of halothane end tidal concentration. The response time for oxygen was 5.23 +/- 1.26 minutes, and that for halothane was 2.67 +/- 1.83 minutes. The average peak overshoot for halothane at the start of the experiment was 26.9%. This pressure controller differs from previously published closed-circuit anesthesia controllers that measure gas volume changes within a mechanical ventilator. A pressure-based controller is easily attached to a standard anesthesia machine and is compatible with modes of ventilation other than controlled mechanical ventilation. The controller used in this study is not designed for clinical use, but was developed to investigate the feasibility of pressure as a basis for gas volume control in closed-circuit anesthesia administration. PMID- 8463803 TI - Integration of monitoring for intelligent alarms in anesthesia: neural networks- can they help? AB - Although there has been a decrease in the number of anesthesia-related critical incidents, there are still opportunities for further improvement. We discuss the potential of integrated monitoring and artificial neural networks as a means of vigilantly watching for patterns in multiple variables to detect incidents and reduce false alarms. We estimate that half the anesthesia-related events could be detected with integrated monitoring using only 5 variables. A review of research using artificial intelligence/expert systems indicates limited potential for success using these tools alone for integrated monitoring in the operating room. We present artificial neural networks as an approach that is more suited to the type of multivariable monitoring and pattern recognition required. Along with rule-based artificial intelligence, these now have the potential to help develop innovative monitoring in the operating room. PMID- 8463804 TI - Construction and use of catheter-manometer systems. AB - The accuracy of invasive arterial blood pressure monitoring is dependent on an adequate damped natural frequency (DNF) and damping factor (DF) of the system. Several factors influencing the DNF and DF were investigated to determine requirements for optimal design of catheter-manometer systems. The frequency sweep method was used in a specially constructed chamber that included linearizing and compensation circuitry. The DNF of isolated 20-gauge cannulae varied from 35.1 to 47.7 Hz. The DNF of 24-gauge cannulae varied from 27.7 to 44.3 Hz. An arterial cannula was found to require a DNF above 40 Hz to prevent the DNF from decreasing to below 25 Hz with the addition of arterial pressure tubing. Arterial pressure tubings exceeding 300 mm in length had DNF values that were unacceptably low even before the addition of arterial cannulae (e.g., the DNF was 23.8 Hz for a 900-mm tubing length, 19.8 Hz for 1,000-mm length, and ranged from 12.9 to 21.4 Hz for 1,200-mm lengths). The 3-way stopcocks and continuous flush devices further decreased the DNF, especially when the diameters were not matched. The percentage decrease caused by 3-way stopcocks and flush devices ranged between 19.5 and 40.8% for 300-mm length tubings and between 2.3 and 25.8% for tubings of 1,200-mm lengths. The radius ratio (outside diameter divided by inside diameter) is introduced as a new method to express the stiffness of arterial pressure tubing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463805 TI - Effect of delay and storage on whole-blood clotting analysis as determined by thrombelastography. AB - The thrombelastogram (TEG) measures the viscoelastic properties of clotting blood, displaying a visual trace of all phases of coagulation and fibrinolysis. Thrombelastography can be performed on whole blood (WBTEG) or on citrated blood or plasma, citrated samples facilitating delayed analysis but requiring recalcification of the sample. The aim of this study was to investigate the effect of delay and storage method on WBTEG measurement. Thrombelastographic analysis of coagulation in whole blood was investigated after delays of 3 and 6 minutes in polystyrene syringes (PS3 and PS6) and 3 minutes in silicone-coated glass tubes (SG3). Thrombelastograms of the delayed samples were compared with those measured immediately. Silicone-coated glass tubes activated coagulation, as seen by shorter r times (p < 0.01), shorter r + k times (p < 0.01), and larger maximum amplitude (ma) values (p < 0.01) compared with TEG values determined immediately after sampling. In the SG3 group, 20% of samples had clotted by 3 minutes, and the use of SG tubes for this purpose cannot be recommended. A delay of 6 minutes in PS had less effect on the activation of clotting in the earlier stages in that the r time was prolonged (p < 0.01). However, there appeared to be some activation later in that k time was shorter (p < 0.01) and ma was wider (p < 0.05). Overall, a 3-minute delay in PS produced the best values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463806 TI - Cable-testing device fails to indicate that hypertension is artifactual. AB - A patient undergoing neurosurgical anesthesia was noted to have a mean systolic/intraarterial pressure of 190/135 mm Hg, whereas the mean systolic/noninvasive blood pressure was 110/77 mm Hg. The problem was traced to a short circuit between the contacts in two adjacent sockets at the transducer-end of the interface cable. The short circuit prevented sufficient attenuation of the excitation voltage from the bedside monitor to the pressure-sensitive bridge circuit of the transducer. A test device (Cable Checker, Viggo-Spectramed, Oxnard, CA) containing a resistance network that could be attached to the interface cable in place of the transducer incorrectly indicated that the cable was functioning properly. The malfunction was confirmed by exposing the transducer to known static pressures. The manufacturer modified the transducer end of its interface cable to reduce the likelihood of a similar problem recurring. Subtleties of the function of the disposable transducer, reasons for a disparity between systolic intraarterial pressures and noninvasive blood pressures, and methods for bedside testing of intraarterial pressure equipment are discussed. PMID- 8463807 TI - The time has come for evolution from the circle breathing system. PMID- 8463808 TI - Current anesthesia breathing systems are just fine. PMID- 8463809 TI - Future anesthesia workstations and today's priorities. PMID- 8463810 TI - Bronchodilator aerosol propellant interferes with an infrared photoacoustic spectrophotometer respiratory gas analyzer. PMID- 8463811 TI - Equipment design errors. PMID- 8463812 TI - Base excess and inappropriate bicarbonate. PMID- 8463813 TI - Mass spectrometry: performance of long catheters. PMID- 8463814 TI - Failure of clinical signs to confirm intravascular placement of a central venous catheter. PMID- 8463815 TI - Peripheral vascular effects on auscultatory blood pressure measurement. AB - Experiments were conducted to examine the accuracy of the conventional auscultatory method of blood pressure measurement. The influence of the physiologic state of the vascular system in the forearm distal to the site of Korotkoff sound recording and its impact on the precision of the measured blood pressure is discussed. The peripheral resistance in the arm distal to the cuff was changed noninvasively by heating and cooling effects and by induction of reactive hyperemia. All interventions were preceded by an investigation of their effect on central blood pressure to distinguish local effects from changes in central blood pressure. These interventions were sufficiently moderate to make their effect on central blood pressure, recorded in the other arm, statistically insignificant (i.e., changes in systolic [p < 0.3] and diastolic [p < 0.02]). Nevertheless, such alterations were found to modify the amplitude of the Korotkoff sound, which can manifest itself as an apparent change in arterial blood pressure that is readily discerned by the human ear. The increase in diastolic pressure for the cooling experiments was statistically significant (p < 0.001). Moreover, both measured systolic (p < 0.004) and diastolic (p < 0.001) pressure decreases during the reactive hyperemia experiments were statistically significant. The findings demonstrate that alteration in vascular state generates perplexing changes in blood pressure, hence confirming experimental observations by earlier investigators as well as predictions by our model studies. PMID- 8463816 TI - The morphology of the sensory neuron in the cockroach femoral tactile spine. AB - 1. The cockroach femoral tactile spine contains a single bipolar sensory neuron. The mechanosensitive dendrite in the wall of the spine leads through the spine lumen to a cell body, and then to an axon that proceeds proximally along the femur. The ultrastructure of the sensory ending has been examined before with electron microscopy. However, the morphology of the complete neuron and its relationship to the general spine structure have not been described before. 2. The tactile spine neuron has been extensively used in electrophysiological studies, including intracellular recordings. Action-potential amplitudes and thresholds were variable and inversely related in intracellular recordings, which could be caused by variability in the location of the action-potential initiation region, the position of the recording electrode, or the neuronal morphology. Attempts to observe the complete neuronal morphology by dye injection were hampered by the opaque and autofluorescent cuticle surrounding the neuron. 3. We examined 10 tactile spine neurons, and their surrounding structures, by taking serial 1-micron sections through the base of the spine, normal to its long axis. The sections were examined with light microscopy, digitized by tracing onto a graphics tablet, and then reassembled with the use of computer software. Reconstructions were made of the borders of the spine cuticle, neuron, neuronal nucleus, glial wrappings, and the main trachea in the spine lumen. 4. There was considerable variability in the size and shape of the neuronal cell body, although the sensory dendrite and axon had more consistent morphologies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463817 TI - Thalamic VPM nucleus in the behaving monkey. I. Multimodal and discriminative properties of thermosensitive neurons. AB - 1. The role of the thalamic ventroposterior medial (VPM) nucleus in the discriminative aspects of nociception and thermoreception was evaluated in alert, trained rhesus monkeys. Single-unit responses were recorded from VPM while the monkeys performed a battery of tasks involving noxious heat, innocuous cool, and air-puff stimuli presented to the face. The discriminative ability of the monkey was compared directly with the responses of single neurons, to determine whether the neuronal response could subserve the monkey's discriminative behavior. 2. Most thermally sensitive neurons exhibited multimodal properties. Only 18% responded exclusively to heat (HT-Heat neurons), whereas 27% responded to innocuous mechanical, as well as noxious mechanical and heat stimuli (WDR-Heat). Twenty-three percent responded to innocuous mechanical stimuli and innocuous skin cooling (Mechano-Cool), and 32% responded to mechanical, innocuous cool, and noxious heat stimuli (WDR-Heat-Cool). 3. Almost all mechanical receptive fields were confined to one division of the trigeminal nerve. This was true for all of the above categories of VPM neurons, even those showing highly convergent properties (WDR-Heat-Cool). 4. Heat-activated neurons produced graded responses to noxious skin heating in the 46 to 49 degrees C range. Stimulus-response functions of neurons that responded to both heat and cool did not differ from those of neurons that responded exclusively to skin heating. 5. When the monkeys were detecting small changes in the intensity of a noxious heat stimulus (e.g., from 47 to 47.1-47.8 degrees C), heat-activated neurons responded to the smallest temperature changes that could be detected by the monkeys. Further, there was a high correlation between the monkey's success in detecting the stimulus changes and the magnitude of the neuronal responses to those changes. 6. Although the responsiveness of VPM cool-activated neurons was not compared with the monkeys' threshold for detecting cooling changes, larger stimulus changes (2 degrees C) that the monkey reliably detected produced significant neuronal responses. Further studies are needed to determine whether VPM neurons respond to the smallest detectable changes in skin cooling. 7. Several thermally sensitive VPM neurons were tested under two attentional conditions: 1) while the monkey was required to attend to a visual stimulus, and 2) while it was required to attend to the thermal stimulus to obtain reward. None showed a significant difference in heat- or cool-evoked activity in the two attentional states.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463818 TI - Contribution of the monkey corticomotoneuronal system to the control of force in precision grip. AB - 1. The contribution of 33 corticomotoneuronal (CM) cells, recorded in the primary motor cortex, to the production of precision grip force has been investigated in four monkeys (Macaca nemestrina). These CM cells were shown, by spike-triggered averaging, to facilitate electromyographic (EMG) activity of hand and forearm muscles. 2. Single-cell recordings were obtained as the monkey performed a low force precision grip task under either isometric or auxotonic conditions. The monkey had to produce independent control of the forces exerted by the thumb and index finger and maintain them for 1-1.5 s. Steady force segments of data were selected trial-by-trial from these hold periods. For each segment the following mean values were determined: 1) CM cell firing rate, 2) EMG activity of facilitated muscles, and 3) index finger, thumb, and total force. 3. Of the 33 CM cells, 18 had a phasic-tonic pattern of discharge during the task, 7 were tonic, 5 had a ramplike increase, and 3 were deactivated during the hold period. 4. Of the 33 cells analyzed, 11 showed a significant positive (P < 0.05) correlation of their mean firing rate with static force; 4 of them had high correlation coefficients (P < 0.001). There was a considerable trial-by-trial variability in the cells' activity-force relationship. Six CM cells had significant negative correlations between their activity and isometric force (5 at the P < 0.001 level), showing lower firing rates with higher forces. 5. The force sensitivity of the CM cells, calculated from the rate-force slopes, was higher for either the thumb or the index finger force. Under isometric conditions the mean rate-force slopes, calculated from the best correlated digit force, was 32.4 Hz/N for eight positively correlated cells and -21.3 Hz/N for the cells with a negative correlation. 6. Correlation between CM cell spike activity and force was more common among neurons with slowly conducting axons (4/6 correlated) than for those with fast axons (13/27). 7. Significant correlations between target muscle EMG and force were always positive. The correlations between CM cell firing rate and target muscle EMG were comparable with those found between firing rate and force. Three of the CM cells with a negative correlation to force also had a negative correlation with EMG in one of their target muscles. 8. Each CM cell facilitated the EMG activity of one to five target muscles; postspike facilitation (PSF) was most common among intrinsic hand muscles (68/82 CM cell/muscle combinations).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463819 TI - Response properties of single units in the dorsal nucleus of the lateral lemniscus and paralemniscal zone of an echolocating bat. AB - 1. Connectional evidence suggests that the dorsal nucleus of the lateral lemniscus (DNLL) and the paralemniscal zone (PL) function as centers for binaural analysis interposed between the superior olivary complex and the midbrain. In addition, the DNLL is known to be a major source of inhibitory input to the midbrain. The aim of this study was to characterize the response properties of neurons in DNLL and PL of the echolocating bat Eptesicus fuscus, a species that utilizes high-frequency hearing and that might be expected to have a large proportion of neurons responsive to interaural differences in sound level. 2. Auditory stimuli were presented monaurally or binaurally to awake animals, and responses of single units were recorded extra-cellularly with the use of glass micropipettes. 3. Below the ventrolateral border of the inferior colliculus is a region that contains large gamma-aminobutyric acid-positive neurons. On the basis of its immunohistochemical reactivity, this entire region could be considered as DNLL. However, within the area, there was an uneven distribution of binaural responses. Caudally, binaural neurons made up 84% (41/49) of those tested, but rostrally only 29% (6/21). For this reason the rostral area is considered as a separate functional subdivision and referred to as the dorsal paralemniscal zone (DPL). PL is located ventral to DPL and medial to the intermediate and ventral nuclei of the lateral lemniscus; in PL 88% (14/16) of neurons were binaural. 4. Most neurons responded only to a contralateral stimulus when sounds were presented monaurally. Out of 49 neurons in DNLL, 42 responded only to a contralateral sound, 1 responded only to an ipsilateral sound, and 6 responded to sound at either ear. In the DPL, all of the 21 neurons tested responded to a contralateral sound and none to an ipsilateral sound. Out of 16 neurons in the PL, 11 responded only to a contralateral sound, 1 responded only to an ipsilateral sound, and 4 responded to sound at either ear. 5. When sounds were presented at both ears simultaneously, several different patterns of binaural interaction occurred. The most common pattern was suppression of the response to sound at one ear by sound at the other ear. In DNLL, 57% (28/49) of neurons showed this type of binaural interaction. Another 10% (5/49) showed facilitation at some interaural level differences and suppression at others, and another 10% (5/49) showed facilitation at some interaural level differences but no suppression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463820 TI - Effects of low-frequency stimulation of the superior colliculus on spontaneous and visually guided saccades. AB - 1. The first experiment of this study determined the effects of low-frequency stimulation of the monkey superior colliculus on spontaneous saccades in the dark. Stimulation trains, subthreshold for eliciting short-latency fixed-vector saccades, were highly effective at biasing the metrics (direction and amplitude) of spontaneous movements. During low-frequency stimulation, the distribution of saccade metrics was biased toward the direction and amplitude of movements induced by suprathreshold stimulation of the same collicular location. 2. Low frequency stimulation biased the distribution of saccade metrics but did not initiate movements. The distribution of intervals between stimulation onset and the onset of the next saccade did not differ significantly from the distribution of intervals between an arbitrary point in time and the onset of the next saccade under unstimulated conditions. 3. Results of our second experiment indicate that low-frequency stimulation also influenced the metrics of visually guided saccades. The magnitude of the stimulation-induced bias increased as stimulation current or frequency was increased. 4. The time course of these effects was analyzed by terminating stimulation immediately before, during, or after visually guided saccades. Stimulation trains terminated at the onset of a movement were as effective as stimulation trains that continued throughout the movement. No effects were observed if stimulation ended 40-60 ms before the movement began. 5. These results show that low-frequency collicular stimulation can influence the direction and amplitude of spontaneous or visually guided saccades without initiating a movement. These data are compatible with the hypothesis that the collicular activity responsible for specifying the horizontal and vertical amplitude of a saccade differs from the type of collicular activity that initiates a saccade. PMID- 8463821 TI - Dynamic clamp: computer-generated conductances in real neurons. AB - 1. We describe a new method, the dynamic clamp, that uses a computer as an interactive tool to introduce simulated voltage and ligand mediated conductances into real neurons. 2. We simulate a gamma-aminobutyric acid (GABA) response of a cultured stomatogastric ganglion neuron to illustrate that the dynamic clamp effectively introduces a conductance into the target neuron. 3. To demonstrate an artificial voltage-dependent conductance, we simulate the action of a voltage dependent proctolin response on a neuron in the intact stomatogastric ganglion. We show that shifts in the activation curve and the maximal conductance of the response produce different effects on the target neuron. 4. The dynamic clamp is used to construct reciprocal inhibitory synapses between two stomatogastric ganglion neurons that are not coupled naturally, illustrating that this method can be used to form new networks at will. PMID- 8463822 TI - Some early travails of tracing axonal pathways in the brain. PMID- 8463823 TI - Changes in protein synthesis accompanying long-term potentiation in the dentate gyrus in vivo. AB - The possibility that the induction of long-term potentiation (LTP) is followed by changes in protein synthesis has been examined using high-resolution two dimensional gel electrophoresis. 35S-methionine, infused into the third ventricle of anesthetized rats, was used to label hippocampal proteins. LTP was induced unilaterally in the dentate gyrus by tetanic stimulation of the perforant path, and followed either for 1 hr or for 3 hr. Two-dimensional gel autoradiographs were quantitatively analyzed using the PDQUEST system (Protein Databases Inc.). One hour after the unilateral induction of LTP, only one protein spot was found to be statistically different in intensity from corresponding spots in the contralateral control side. Three hours after LTP, however, 11 spots were found to have altered densities. Examination of basic proteins using the nonequilibrium pH gel electrophoresis system revealed changes in three proteins in the 3 hr group. Reductions as well as increases in spot intensities were observed. The results indicate that LTP is associated with a complex pattern of changes in protein synthesis. PMID- 8463824 TI - Regionalization and intersegmental coordination of rhythm-generating networks in the spinal cord of the chick embryo. AB - We have examined the regionalization and coordination of rhythm-generating networks in the isolated spinal cord of the chick embryo between embryonic days 9 and 13, by recording the pattern of rhythmic activity recorded from muscle nerves and ventral roots following a variety of lesions. We found that the capacity for rhythmic activity is distributed along the rostrocaudal axis of the cord but can be expressed in a single, isolated segment. Specializations within the lumbosacral cord were investigated by isolating particular regions and recording their motor output. The rostral part of the lumbosacral cord generates more cycles than the caudal part, and this difference becomes more pronounced with development. In the unlesioned cord, motoneuron activity is synchronized along the rostrocaudal axis. Lesion experiments revealed that the synchronization of motoneuron activity and the synaptic drive to caudal motoneurons is mediated in part by propriospinal pathways traveling in the ventrolateral white matter tracts and by synaptic interactions within the gray matter. The dorsal fiber tracts may also be involved but their effects appear to be weak. Lesions in dorsal-ventral and mediolateral planes were used to localize regions critical for rhythmogenesis and for the alternation of flexor and extensor motoneurons. Rhythmic activity with alternation persisted in spinal cords in which the dorsal and medial half had been removed. Severe medial or dorsal lesions, resulting in a thin strip of lateral or ventral gray matter, altered the phasing of motoneuron activity from alternating to synchronous without effects on cycle timing. These results suggest that the critical neural components for alternation are located close to and dorsomedial to the lateral motor column, and that the capacity for rhythmogenesis is distributed widely throughout the ventral gray matter and is not localized to specific nuclei. PMID- 8463825 TI - Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. AB - The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors. Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction. Consistent with the high degree of sequence similarity to mGluR2, mGluR3 closely resembles mGluR2 in its agonist selectivity; the potency rank order of agonists is L-glutamate > trans-1 aminocyclopentane-1,3-dicarboxylate > ibotenate > quisqualate. mGluR4 is totally different in its agonist specificity from any other member of the metabotropic receptors. This receptor potently reacts with L-2-amino-4-phosphonobutyrate (L AP4) in a stereo-selective manner and moderately responds to L-serine-O phosphate. mGluR4 thus corresponds well to the putative L-AP4 receptor characterized from brain preparations. Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate putamen, and in granule cells of the hippocampal dentate gyrus. The expression pattern of mGluR4 mRNA is more restricted, and this expression is prominent in the cerebellum, olfactory bulb, and thalamus. Furthermore, the mGluR3 mRNA, unlike the other mRNAs for the metabotropic receptors, is highly expressed in glial cells throughout the brain regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463826 TI - Inhibition of brain protein synthesis by cycloheximide does not affect formation of long-term memory in honeybees after olfactory conditioning. AB - The honeybee forms a long-term memory in different training situations that lasts for a lifetime, but the cellular mechanisms of long-term memory formation are not known. We analyzed the dependency of long-term memory on the de novo brain protein synthesis. The protein synthesis inhibitor cycloheximide was injected via the median ocellus directly into the brain. 3H-leucine incorporation into brain proteins was inhibited by > 95% for > 3 hr. The time of protein synthesis inhibition was prolonged by a second injection of the same dose. Worker honeybees were conditioned to an olfactory stimulus at different times before and after injection. The proboscis extension response (PER) of bees restrained in tubes was classically conditioned with sugar water applied first to the antennae followed by feeding (unconditioned stimulus) paired with odor presentation (conditioned stimulus). The bees were tested by presenting the odor alone at different times up to 24 hr after injection. No significant reduction in the probability of the conditioned response in cycloheximide-treated bees was found when compared to the Ringer-injected controls in 4 series of experiments. Since protein synthesis was inhibited between 7 hr pre- and 7 hr postconditioning without affecting the formation of long-term memory, a possible role of de novo protein synthesis in the formation of long-term memory after olfactory conditioning of the PER is not supported by these experiments. PMID- 8463827 TI - Clonal patterns of cell proliferation, migration, and dispersal in the brainstem of the chicken embryo. AB - Retroviral-mediated gene transfer was used to study clonal patterns of proliferation, migration, and dispersal in the brainstem of the chicken embryo. Clones were generated at stages 13-17 (Hamburger and Hamilton, 1951), a period of neurogenesis in the brainstem neural tube subsequent to the formation of rhombomeres. Clones were examined in separate experiments at stages 24-27, when many neurons migrate and differentiate; at stages 28-29, when brainstem nuclei begin to form; and at stages 34-35, when brainstem nuclei are fully formed. Stages 24-29 are characterized by a general variability in proliferative kinetics and migratory behavior. Clone sizes range from 1 to 29 cells, and migration patterns range from strictly radial (i.e., normal to the ventricular surface) to combined radial and tangential (i.e., perpendicular to the radial component). There is, however, an underlying systematic variation: (1) clones exhibiting tangential migration contain on average more cells than clones exhibiting only radial migration, and (2) the proportion of tangentially migrating clones increases from medial to lateral. By stages 34-35 some individual clones have apparently dispersed to disparate neuronal groups. The regional diversity observed among clones suggests that position along the mediolateral axis may determine the proliferative potential of progenitors and the migratory behavior and subsequent dispersal of their descendants. PMID- 8463828 TI - Two-dimensional spatiotemporal coding of linear acceleration in vestibular nuclei neurons. AB - Response properties of vertical (VC) and horizontal (HC) canal/otolith-convergent vestibular nuclei neurons were studied in decerebrate rats during stimulation with sinusoidal linear accelerations (0.2-1.4 Hz) along different directions in the head horizontal plane. A novel characteristic of the majority of tested neurons was the nonzero response often elicited during stimulation along the "null" direction (i.e., the direction perpendicular to the maximum sensitivity vector, Smax). The tuning ratio (Smin gain/Smax gain), a measure of the two dimensional spatial sensitivity, depended on stimulus frequency. For most vestibular nuclei neurons, the tuning ratio was small at the lowest stimulus frequencies and progressively increased with frequency. Specifically, HC neurons were characterized by a flat Smax gain and an approximately 10-fold increase of Smin gain per frequency decade. Thus, these neurons encode linear acceleration when stimulated along their maximum sensitivity direction, and the rate of change of linear acceleration (jerk) when stimulated along their minimum sensitivity direction. While the Smax vectors were distributed throughout the horizontal plane, the Smin vectors were concentrated mainly ipsilaterally with respect to head acceleration and clustered around the naso-occipital head axis. The properties of VC neurons were distinctly different from those of HC cells. The majority of VC cells showed decreasing Smax gains and small, relatively flat, Smin gains as a function of frequency. The Smax vectors were distributed ipsilaterally relative to the induced (apparent) head tilt. In type I anterior or posterior VC neurons, Smax vectors were clustered around the projection of the respective ipsilateral canal plane onto the horizontal head plane. These distinct spatial and temporal properties of HC and VC neurons during linear acceleration are compatible with the spatiotemporal organization of the horizontal and the vertical/torsional ocular responses, respectively, elicited in the rat during linear translation in the horizontal head plane. In addition, the data suggest a spatially and temporally specific and selective otolith/canal convergence. We propose that the central otolith system is organized in canal coordinates such that there is a close alignment between the plane of angular acceleration (canal) sensitivity and the plane of linear acceleration (otolith) sensitivity in otolith/canal-convergent vestibular nuclei neurons. PMID- 8463829 TI - Activity of neurons in anterior inferior temporal cortex during a short-term memory task. AB - Inferior temporal (IT) cortex of primates is known to play an important role in visual memory. Previous studies of IT neurons during performance of working memory tasks have found modulation of responses when a current stimulus matched an item in memory; however, this effect was lost if other stimuli intervened in the retention interval. To examine how IT cortex retains memories while new stimuli are activating the cells, we recorded from IT neurons while monkeys performed a delayed matching-to-sample task, with multiple intervening items between the sample and matching test stimulus. About half of the cells responded differently to a test stimulus if it matched the sample, and this difference was maintained following intervening stimuli. For most of the affected cells, the responses to matching stimuli were suppressed; however, for a few cells the opposite effect was seen. Temporal contiguity alone could not explain the results, as there was no modulation of responses when a stimulus on one trial was repeated on the next trial. Thus, an active reset mechanism appears to restrict the memory comparison to just the stimuli presented within a trial. The suppressive effects appear to be generated within or before IT cortex since the suppression of response to matching stimuli began almost immediately with the onset of the visual response. The memory of the sample stimulus affected not only the responses to matching stimuli but also those to nonmatching stimuli. There was suggestive evidence that the more similar a nonmatching stimulus to the sample, the more the response was suppressed. About a quarter of the cells showed stimulus-selective activity in the delay interval following the sample. However, this activity appeared to be eliminated by intervening stimuli. Thus, it is unlikely that delay-interval activity in IT contributed to the performance of this particular version of delayed matching to sample. To determine how much information about the match-nonmatch status of the stimulus was conveyed by individual neurons, we analyzed the responses with discriminant analysis. The responses of an individual IT neuron could be used to classify a stimulus as matching or nonmatching on about 60% of the trials. To achieve the same performance as the animal would require averaging the responses of a minimum of 25 IT neurons. There was no evidence that mnemonic information was carried by temporal variations in the spike trains. By contrast, there was a modest amount of temporal variation in sensory responses to different visual stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463830 TI - Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic "scotomas". AB - The spatial memory functions of the monkey's prefrontal cortex were examined with oculomotor delayed-response (ODR) paradigms that required the animal to remember the spatial location of peripheral visual cues, while maintaining fixation on a central visual target during the presentation of each cue and during a subsequent 1.5-8 sec delay period. Four rhesus monkeys received unilateral or serial prefrontal lesions in and around the principal sulcus after they reached criterion performance on the ODR tasks. Unilateral lesions disrupted the performance of memory-guided eye movements to spatial cues in the visual field contralateral to the hemisphere in which the lesion was placed. Memory-guided eye movements to ipsilateral cues were mildly affected by unilateral lesions, and these lesions had little or no effect on performance in visually guided control tasks. With addition of a second lesion in the opposite hemisphere, the deficit was extended to include the opposite hemifield. The impairment was characterized by eye movements of inappropriate direction, and, excepting the one lesion that extended into the frontal eye field region of the arcuate sulcus, saccadic reaction times and velocities were the same before and after the lesions. The effect of the lesions was delay dependent: performance was rarely altered at the shortest (1.5 sec) delay but became progressively worse as the delay period was lengthened. The present results strengthen the evidence that the delayed-response deficits of monkeys with prefrontal lesions are caused by failure to maintain a transient memory "trace" in working memory, and indicate for the first time that working memory mechanisms are lateralized: memories for visuo-spatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. These findings provide evidence for the concept of mnemonic hemianopias and mnemonic scotomas, that is, memory deficits for particular hemifields or visual field locations, unaccompanied by simple sensory or motor deficits. PMID- 8463832 TI - Testosterone enhancement of the nerve cell body response to injury: evidence using in situ hybridization and ribosomal DNA probes. AB - In axotomized peripheral motoneurons capable of successful regeneration, one of the earliest morphological indicators of the injury response occurs within the nucleolus. In the initial part of this investigation, we mapped the nucleolar response of injured adult hamster facial motoneurons from a molecular perspective, utilizing in situ hybridization and ribosomal DNA probes complementary to stable rRNA. Recently, we have discovered that the gonadal steroid, testosterone propionate (TP), accelerates recovery from facial paralysis in the hamster by increasing the rate of regeneration of the fastest regrowing axons. In the second part of this study, the hypothesis that TP accomplishes these effects on facial nerve regeneration through an enhancement of the nerve cell body response to injury was tested using in situ hybridization and rDNA probes. Adult intact male hamsters were subjected to right facial nerve axotomies at the stylomastoid foramen. One-half of the axotomized animals received subcutaneous implants of TP, with the remainder sham implanted. In situ hybridization with tritiated rDNA probes was accomplished and levels of hybridizable rRNA assessed both qualitatively and quantitatively. Axotomy alone induced an upregulation in rRNA levels, with peak changes occurring by 24 hr postoperative and continuing through postoperative day 4. These molecular changes in the nucleolar response preceded, by a full day, any morphological signs of the nucleolar reactive pattern previously found in this cell type, and, as such, point to the usefulness of in situ hybridization as a tool to identify the earliest events associated with the axon reaction. A secondary smaller increase in rRNA levels was observed during the later stages of regeneration. TP significantly augmented the ribosomal response to injury, with levels of rRNA increased as early as 6 hr and the magnitude of the response greater than that occurring following axotomy alone. These results provide the first mechanistic step in the identification of the cellular processes underlying gonadal steroid augmentation of neuronal reparative processes. We conclude that TP accelerates the "switch" from a normal to a reparative state and suggest that this priming effect may be causally related to the differential effects of TP on the regenerative properties of this cell type. PMID- 8463831 TI - Single mossy fiber axonal systems of human dentate granule cells studied in hippocampal slices from patients with temporal lobe epilepsy. AB - Previous histological and immunocytochemical studies suggest that reorganization of the dentate granule cell axons, the mossy fibers, can occur in epileptic human hippocampus (Sutula et al., 1989; Houser et al., 1990; Babb et al., 1991) and in animal models of epilepsy (Tauck and Nadler, 1985; Sutula et al., 1988; Cronin et al., 1992). However, neuroanatomical analyses of the trajectory and morphology of reorganized axons are not yet available. The present study was conducted to investigate single dentate granule cell axonal systems in human epileptic hippocampus. Individual mossy fibers were directly visualized by injecting a tracer (biocytin or Lucifer yellow) intracellularly in hippocampal slices prepared from temporal lobes that were surgically removed from patients for treatment of intractable epilepsy. Two major arborization patterns were identified: (1) the parent axons extended to and coursed through the hilus toward CA3, leaving collaterals along their paths in the hilus (N = 19 neurons); (2) in addition to the aforementioned axonal system, collateral(s) branched from the parent axon near the soma and projected to the granule cell layer and molecular layer, forming an aberrant axonal pathway (N = 9 neurons). These aberrant collaterals bore large boutons similar to those of the hilar axons and formed extensive plexuses in the granule cell layer and/or in the molecular layer. The summed length of collaterals in the granular/molecular layers was 1110.8 microns on average, which was one-fourth of the total summed length of the mossy fibers (3698.5 microns on average). The size of the somata in neurons that had aberrant collaterals was significantly larger than that of neurons without such collaterals (p < 0.025). In four cases, filopodium-like fine processes were present near the axon hillock and proximal parts of the parent axon, suggesting that the aberrant collateral formation might be an ongoing process in these tissues. The lack of control slices from normal living human hippocampus makes it difficult to assess to what extent the present findings are epilepsy associated. However, the presence of aberrant mossy fiber collaterals in the hippocampi used in the present study has been confirmed by Timm's staining and/or dynorphin immunohistochemistry in comparison with nonepileptic autopsy material, indicating its relation to epilepsy (Babb et al., 1991, 1992). At present, there seems to be a consensus that the projection of mossy fiber collaterals to the supragranular layer is a rare occurrence in normal rats (Lorento de No, 1934; Claiborne et al., 1986; Seress et al., 1991; present study), normal monkeys (Seress et al., 1991), and normal humans (Houser et al., 1990).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8463833 TI - Nerve growth factor is a potent inducer of proliferation and neuronal differentiation for adult rat chromaffin cells in vitro. AB - Adult rat chromaffin cells in vitro show a large proliferative response to NGF, followed by neuronal differentiation. Infection of replicating chromaffin cells with a retrovirus carrying the Escherichia coli beta-galactosidase (beta-gal) gene demonstrates beta-gal expression in cells that continue to multiply, that differentiate into neurons, and that become static. The effects of NGF on proliferation and differentiation are abolished by the protein kinase inhibitors K252a and staurosporine, and by cholera toxin, an activator of adenylate cyclase. They are diminished, but not abolished, by high concentrations of dexamethasone. Both cholera toxin alone and phorbol myristate acetate (PMA), an activator of protein kinase C, elicit small and inconsistent mitogenic responses. The responses to PMA cannot be shown to be additive with the effects of NGF. NGF is a known mitogen and neuritogen for chromaffin cells from neonatal rats, but has not previously been believed to affect similarly chromaffin cells from adults. The present findings suggest that portions of NGF signaling pathways might continue to be involved in regulating proliferation of adult rat chromaffin cells in vivo, and might be constitutively activated in PC12 cells and other adrenal medullary tumors. They further suggest that rat chromaffin cells might be propagated in vitro to obtain large numbers of sympathetic neurons expressing normal or exogenous genes. PMID- 8463834 TI - The spectral sensitivity of dark- and light-adapted cat retinal ganglion cells. AB - The spectral sensitivity of cat retinal ganglion neurons (RGNs) was determined by means of extracellular recordings under scotopic and photopic conditions, in both receptive field center and surround. Test stimuli were presented either as square wave single flashes or as flicker stimuli. Chromatic adaptation was achieved by a large steady monochromatic background field. In the dark-adapted state the spectral sensitivity of the majority of ganglion cells (92%) was rod mediated (peak sensitivity at 501 nm). Under photopic conditions all neurons received input from a long-wavelength-sensitive (L-cone) system with a peak sensitivity of 550 nm. Input from a short-wavelength-sensitive (S-cone) system (peak sensitivity at 450 nm), however, was found only in 15% of the ganglion cells. A small cell population (8%) located within the area centralis revealed a different receptive field organization. In these cells, spectral sensitivity in the field center peaked at 520 nm in the dark-adapted state and response threshold was about 1 log unit higher than in cells with a peak sensitivity of 501 nm. Critical flicker fusion was reached at 60-70 Hz, a frequency that usually is mediated by cones. We therefore postulate an additional input of a midspectral receptor system (M system) other than rods in cat retinal ganglion cells. This input was found only in the receptive field center of some ganglion cells in the dark-adapted state, whereas the surround sensitivity was mediated in all cells by rod signals under scotopic and predominantly by L-cone signals under photopic conditions. PMID- 8463835 TI - Immunocytochemical localization of a neuronal nicotinic receptor: the beta 2 subunit. AB - We have characterized in adult rat the tissue-specific expression of the nicotinic ACh receptor (AChR) beta 2-subunit using antisera raised against fusion protein constructs. Immunohistochemical localization revealed immunoreactivity distributed throughout the neuraxis. Overall, beta 2-like immunoreactivity (beta 2-LI) correlated well with in situ localization of beta 2 transcript in neuronal cell bodies. Particularly strong labeling was detected in the thalamus, and scattered other regions, whereas relatively weak staining was observed in the hypothalamus and amygdala. At the cellular level, beta 2-LI appeared to be exclusively neuronal and concentrated predominantly in perikarya, although strongly positive dendrites (cerebral cortical pyramidal neurons, cerebellar Purkinje cells) and axon terminals (e.g., striatum) were detected. At the ultrastructural level, beta 2-LI was membrane associated, with strong staining observed in endoplasmic reticulum and cytoplasmic transport vesicles. beta 2-LI was rarely detected at synapses. The widespread distribution of beta 2 suggests it may serve as a common subunit in different AChR combinations in various brain regions. Regulation of the expression of beta 2-subunit appears to be relatively unrestrained, with an apparent excess of protein synthesized in the cytoplasm relative to that which ultimately arrives at functional targets in the plasma membrane. PMID- 8463836 TI - Contrasting immunohistochemical localizations in rat brain of two novel K+ channels of the Shab subfamily. AB - We have localized CDRK and DRK1, two novel K+ channels of the Shab subfamily by immunohistochemistry. The two channels are closely related in structure with about 90% amino acid identity in the N-terminal and middle portions and 60% identity in the C-terminal region. We observe striking differences in cellular localizations of the two channels. DRK1 tends to localize to cell bodies and proximal dendrites discretely, while CDRK is diffusely present in cell bodies and is also found on fibers in specific brain areas. In the cerebral cortex DRK1 is localized to pyramidal cells, whereas CDRK occurs in small cells, presumably interneurons. These localizations may reflect specialized delayed rectifier functions and targeting properties manifested differentially by K+ channel subfamily members. PMID- 8463837 TI - Neurofibromin is enriched in the endoplasmic reticulum of CNS neurons. AB - NF1 patients display CNS abnormalities including learning disabilities, clumsiness, astrocytomas, and abnormalities on magnetic resonance imaging exams. To determine whether the cellular and neuroanatomical distribution of neurofibromin reveals possible function for neurofibromin in the brain, we stained rat brain tissue sections with anti-neurofibromin antibodies. Neurofibromin is highly enriched in large projection neurons, such as cortical and hippocampal pyramidal cells and cerebellar Purkinje cells. Neurofibromin is present in cell bodies and in axons, but is highly enriched in dendrites. Immunoelectron microscopic analysis demonstrates that NF1 is associated with smooth vesiculotubular elements and cisternal stacks and with multivesicular bodies in the cell body and dendrites, but not with the plasma membrane, nucleus, nuclear envelope, Golgi apparatus, mitochondria, or rough endoplasmic reticulum. The preferential localization of neurofibromin to the smooth endoplasmic reticulum, together with evidence that neurofibromin modulates ras GTPase activity, suggests that some, if not all, of the CNS manifestations of NF1 might result from the altered expression of neurofibromin in neurons, perhaps through disruption of Ca2+ signaling, translocation of organelles, or endocytic pathways. PMID- 8463838 TI - Thalamocortical response transformations in simulated whisker barrels. AB - Layer IV of rodent somatosensory cortex contains identifiable networks of neurons, called "barrels," that are related one-to-one to individual whiskers on the face. A previous study (Simons and Carvell, 1989) described differences between the response properties of thalamic and cortical vibrissa neurons and proposed that these transformations can be explained by several features of barrel anatomy and physiology: nonlinear neuronal properties, strongly responsive inhibitory and less responsive excitatory neurons, convergent thalamic inputs to cells of both types, and interconnections among barrel neurons. In the present study these features were incorporated into a computational model in order to test their explanatory power quantitatively. The relative numbers of excitatory and inhibitory cells and the relative numbers of synapses of thalamic and intrabarrel origin were chosen to be consistent with available light and electron microscopic data. Known functional differences between excitatory and inhibitory barrel neurons were simulated through differences in spike activation functions, refractory periods, postsynaptic potential decay rates, and synaptic strengths. The model network was activated by spike trains recorded previously from thalamic neurons in response to three different whisker deflection protocols, and output, which consisted of spikes generated by the simulated neurons, was compared to data from our previous neurophysiological experiments. For each type of whisker stimulus, the same set of parameter values yielded accurate simulations of the cortical response. Realistic output was obtained under conditions where each barrel cell integrated excitatory and inhibitory synaptic inputs from a number of thalamic and other barrel neurons and where the ratios between network excitation, network inhibition, and thalamic excitation were approximately constant. Several quantities are defined that may be generally useful in characterizing neuronal networks. One important implication of the results is that thalamic relay neurons not only provide essential drive to the cortex but could, by changing their tonic activities, also directly regulate the tonic inhibition present in the cortex and thereby modulate cortical receptive field properties. PMID- 8463839 TI - Harmaline-induced impairment of Pavlovian conditioning in the rabbit. AB - In this study we examined the effects of harmaline on Pavlovian conditioning of the rabbit's nictitating membrane response. The acquisition of conditioned responses was determined during a single session consisting of 120 pairings of a tone-conditioned stimulus with a corneal air puff unconditioned stimulus. Harmaline severely retarded (5 mg/kg) or completely blocked (10 and 20 mg/kg) acquisition of conditioned responses. The blocked or retarded acquisition of conditioned responses could still be detected when the rabbits were tested 2 d after cessation of drug injections, suggesting that harmaline was affecting acquisition and not the motoric expression of conditioned responses. Control experiments established that harmaline (5 mg/kg) did not affect (1) baseline levels of responding, (2) the level of non-associative responding to the conditioned stimulus, (3) the amplitude or any of the temporal characteristics of the unconditioned response, (4) the development of habituation to the unconditioned stimulus, and (5) the threshold of the unconditioned stimulus for eliciting the unconditioned response. However, harmaline did produce a 12 dB increase in the intensity threshold of the conditioned stimulus for eliciting conditioned responses. We concluded that the primary effect of harmaline was to impair stimulus processing within brainstem circuits such as to reduce the excitatory properties of the conditioned stimulus, thus retarding its entry into associative learning. The results were discussed with respect to the possible role of the inferior olive in associative learning. PMID- 8463840 TI - Recoverable and nonrecoverable deficits in conditioned responses after cerebellar cortical lesions. AB - This study reexamined the effects of unilateral damage to cerebellar hemispheral lobule VI on the rabbit's conditioned nictitating membrane (NM) response. Extensive unilateral removal of hemispheral lobule VI in 11 rabbits impaired ipsilateral conditioned responses as reflected by reductions of 52% in mean frequency and 53% in mean amplitude during test trials on the first postoperative session. The decreases in the amplitude and frequency of conditioned responses were highly correlated (r = 0.82). The frequency of conditioned responses recovered to control levels but their amplitudes remained reduced such that the correlation between these two measures of responding was no longer significant by the 12th postoperative conditioning session. The decrease in the amplitude of conditioned responses was not accompanied by changes in onset latency or rise time. There was no significant impairment of conditioned responses in surgical controls and animals with only partial damage to hemispheral lobule VI. It was concluded that hemispheral lobule VI plays an important role in the regulation of motor centers in the brainstem so as to facilitate the initiation and optimum execution of the conditioned NM reflex. This cortical regulation of the conditioned NM response may contain learned elements; however, these cannot be resolved with lesion methods, nor has their existence been proven in this or other lesion studies. Nevertheless, the results of this study do demonstrate that the cerebellar cortex cannot be considered as the single locus necessary for NM conditioning. PMID- 8463841 TI - Phenotypic plasticity in adult sympathetic ganglia in vivo: effects of deafferentation and axotomy on the expression of vasoactive intestinal peptide. AB - The expression of neurotransmitters/neuromodulators in sympathetic neurons is regulated by anterograde and retrograde mechanisms. We have examined the role of such mechanisms in the regulation of the neuropeptide vasoactive intestinal peptide (VIP). The adult rat superior cervical ganglion (SCG) contains low levels of peptide-like immunoreactivity (IR) and mRNA for VIP. Some VIP-IR nerve processes, but only a few VIP-IR cell bodies, are detectable. Previous evidence demonstrates, however, that after the SCG is placed in organ culture for 48 hr, the level of VIP-IR and VIP mRNA and the number of VIP-IR cell bodies and fibers increase considerably. Two of the possible causes for these changes in peptide expression in sympathetic neurons are deafferentation and axotomy, both of which occur when the SCG is placed in culture. To determine the importance of deafferentation, the preganglionic cervical sympathetic trunk was cut and the ganglion left in situ. Forty-eight hours later, VIP-IR increased twofold. A corresponding increase in the number of VIP-IR nerve processes was seen, but there was no detectable change in the number of VIP-IR cell bodies. The content of VIP/PHI mRNA also increased by 1.8-fold. The effect of axotomy on VIP-IR was examined by cutting the postganglionic internal and external carotid nerves and leaving the ganglion in situ. Forty-eight hours later, the level of VIP-IR increased 22-fold, many immunostained neurons were found, and the content of VIP mRNA increased over fivefold. After either deafferentation or axotomy, changes in VIP-IR were accompanied by comparable changes in the related molecule peptide histidine isoleucine amide (PHI)-IR. Neuropeptide Y-IR, on the other hand, decreased after deafferentation and increased only twofold after axotomy. The results indicate plasticity in the expression of VIP- and PHI-IR in adult sympathetic neurons in vivo, and suggest that the changes previously seen in organ culture were primarily a response to axotomy. PMID- 8463842 TI - Expression of glutamate receptor genes in white matter: developing and adult rat optic nerve. AB - We have identified the glutamate receptor genes expressed by developing and adult rat optic nerve. Results from PCR suggested that of the ionotropic glutamate receptor (GluR) gene family, only GluR1 and GluR3 subunits are expressed by optic nerve. However, Northern blot analysis demonstrated that only the GluR1 subtype is expressed at appreciable levels. In situ hybridization histochemistry of GluR1 was performed and a diffuse pattern of expression was observed in both postnatal day 15 and adult optic nerve. Restriction mapping of the GluR1 PCR product indicated the expression of the flip alternative splice version in optic nerve. The detected GluR1 message was not due to axons because no loss of expression was observed after the degeneration of axons. PCR analysis also revealed the presence of a metabotropic glutamate receptor in optic nerve. PMID- 8463844 TI - Bag cell extract inhibits tail-siphon withdrawal reflex, suppresses long-term but not short-term sensitization, and attenuates sensory-to-motor neuron synapses in Aplysia. AB - The peptides released from the bag cells (bag cell peptides, BCPs) in Aplysia californica are responsible for eliciting or modulating a repertoire of behaviors preceding and accompanying egg laying. Our interest was in determining to what extent behaviors that can occur simultaneously with egg laying are modulated. To address this issue, we examined the effects of an extract (bag cell extract, BCE) that contained BCPs, as well as egg-laying hormone (ELH), an identified BCP, on both the tail-siphon withdrawal reflex and the ability of that reflex to exhibit sensitization, a simple form of nonassociative learning. In addition, we examined the ability of BCE, as well as the individual BCPs, to modulate a component of the circuitry of the reflex. Behavioral experiments indicated that BCE inhibited the baseline withdrawal reflex and suppressed long-term sensitization of the reflex while leaving short-term sensitization unaffected. These effects were not observed in animals receiving an extract of a control ganglion or in animals receiving ELH, and therefore may be attributed to the actions of one or more BCPs, but presumably not to ELH alone. Electrophysiological experiments revealed that BCE also attenuated the monosynaptic EPSP elicited in tail motor neurons by tail sensory neurons. In subsequent experiments in which the BCPs were individually applied, only one BCP, beta-BCP, significantly attenuated the EPSPs. This effect was independent of narrowing of the presynaptic action potential. Taken together, these results suggest a novel behavioral modification attributed to BCPs, inhibition of the tail-siphon withdrawal reflex, and suggest a possible locus of action and peptide candidate for this effect. In addition, these experiments raise the possibility that BCPs may exert a long-lasting effect (> 24 hr), selectively blocking a simple form of long-term memory. PMID- 8463843 TI - Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. AB - The progressive neurodegeneration of Alzheimer's disease has been hypothesized to be mediated, at least in part, by beta-amyloid protein. A relationship between the aggregation state of beta-amyloid protein and its ability to promote degeneration in vitro has been previously suggested. To evaluate this hypothesis and to define a structure-activity relationship for beta-amyloid, aggregation properties of an overlapping series of synthetic beta-amyloid peptides (beta APs) were investigated and compared with beta AP neurotoxic properties in vitro. Using light microscopy, electrophoresis, and ultracentrifugation assays, we found that few beta APs assembled into aggregates immediately after solubilization, but that over time peptides containing the highly hydrophobic beta 29-35 region formed stable aggregations. In short-term neuronal cultures, toxicity was associated specifically with those beta APs that also exhibited significant aggregation. Further, upon the partial reversal of beta 1-42 aggregation, a concomitant loss of toxicity was observed. A synthetic peptide derived from a different amyloidogenic protein, islet amyloid polypeptide, exhibited aggregation but not toxicity, suggesting that beta AP-induced neurotoxicity in vitro is not a nonspecific reaction to aggregated protein. The correlation between beta AP aggregation and neurotoxicity was also observed in long-term neuronal cultures but not in astrocyte cultures. These data are consistent with the hypothesis that beta-amyloid protein contributes to neurodegeneration in Alzheimer's disease. PMID- 8463845 TI - Casein kinase II phosphorylates the synaptic vesicle protein p65. AB - p65 (synaptotagmin), an abundant synaptic vesicle protein, has been implicated in the processes of vesicle docking and fusion. To characterize further the properties of this important neuronal protein, we have investigated its phosphorylation in vitro. Immunoprecipitation of p65 results in coprecipitation of a protein kinase that phosphorylates p65 as well as syntaxin, a plasma membrane protein that interacts with p65. p65 is phosphorylated on a threonine residue (Thr-128) within the cytoplasmic domain near the transmembrane region. The coprecipitating protein kinase was identified as casein kinase II based on its catalytic properties, the sequence surrounding Thr-128, and Western blot analysis of the anti-p65 immunoprecipitates. Affinity chromatography utilizing bacterially expressed fragments of p65 demonstrated that casein kinase II interacts with a domain of p65 distinct from the phosphorylation site. In a synaptic vesicle fraction, the phosphorylation of p65 is stimulated by sphingosine and by detergent solubilization, suggesting that p65 phosphorylation may be subject to regulatory processes. PMID- 8463846 TI - Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. AB - Among the many issues surrounding the involvement of the cerebellum in motor learning, the relative roles of the cerebellar cortex and cerebellar nuclei in Pavlovian conditioning have been particularly difficult to assess. While previous studies have investigated the effects of cerebellar cortex lesions on the acquisition and retention of conditioned movements, we have examined the effects of these lesions on the timing of Pavlovian eyelid responses. The rationale for this approach arises from previous studies indicating that this timing is a component of Pavlovian eyelid responses that is learned and that involves temporal discrimination. To permit within-animal comparisons, rabbits were trained to produce differently timed responses to high- and low-frequency auditory conditioned stimuli (CSs). Before the lesion the conditioned responses to both CSs were appropriately timed--each peaked near the time at which the unconditioned stimulus was presented for that CS. However, after the lesion both CSs could elicit similarly timed conditioned responses that peaked inappropriately at very short latencies. The changes in responses timing were sensitive to the size of the lesion, particularly its rostral-caudal extent. Similar results were obtained in animals trained with one CS, indicating that the disruption of response timing is not related to impaired auditory discrimination. Because response timing is learned and therefore requires synaptic plasticity, these data suggest that there are at least two sites of plasticity involved in the motor expression of Pavlovian eyelid responses. Plasticity at one site is necessary for the learned timing of conditioned responses, while plasticity at another site is revealed by the inappropriately timed responses observed following removal of the cerebellar cortex. This lesion-induced dissociation of the expression of motor responses and their learned timing supports a synthesis of competing views by suggesting that motor learning involves both the cerebellar cortex and cerebellar nuclei. We hypothesize that motor learning involves a decrease in strength of the granule cell-Purkinje cell synapses (e.g., Ito and Kano, 1982) in the cerebellar cortex and an increase in strength of the mossy fiber-cerebellar nuclei synapses (e.g., Racine et al., 1986). Finally, these data suggest that the cerebellar cortex may mediate the temporal discriminations that are necessary for the learned timing of conditioned responses. PMID- 8463847 TI - Microstimulation in visual area MT: effects of varying pulse amplitude and frequency. AB - We have previously shown that perceptual judgements of motion direction are based in part on the activity of direction selective neurons in extrastriate visual area MT (Salzman et al., 1990, 1992). In those experiments, we applied low amplitude microstimulation pulses (10 microA, 200 Hz) to clusters of MT neurons whose preferred directions were similar. The effect of microstimulation was to bias the monkeys' choices on a direction discrimination task toward the preferred direction of neurons at the stimulation site. The results suggest that microstimulation generated a directionally specific cortical signal by activating selectively neurons near the electrode tip. To test this notion more directly, we have now examined the behavioral effects of varying current amplitude, current frequency, and electrode position. In the majority of experiments, the directional bias in the monkeys' choices was reduced or eliminated as current amplitude increased to 80 microA. In addition, 80 microA stimulating pulses frequently impaired overall performance as measured by the percentage of correct responses. This decrement in performance indicated that 80 microA pulses introduced "noise" into the neural circuitry encoding motion direction, presumably by increasing current spread to activate a larger population of neurons representing all directions of motion. In contrast, increasing current frequency to 500 Hz (10 microA pulses) preserved the directional specificity of microstimulation effects. The precise position of the stimulating electrode also influenced the magnitude of microstimulation effects; in some cases, differences in position on the order of 100 microns determined whether an experiment yielded a very large effect or no effect at all. Thus, directionally specific activation of cortical circuitry within MT can be disrupted by increases in current spread or by small changes in electrode position. These observations suggest that the effects of low-amplitude microstimulation depend upon direct activation of a well localized population of neurons. PMID- 8463848 TI - Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells. AB - The diverse array of neurons and glia in the mammalian cerebral cortex arises from proliferating cells of the ventricular zone that surrounds the lateral ventricles of the developing brain. A fundamental but unresolved question is whether the individual cells of the ventricular zone are committed to producing progeny of only one particular phenotype or whether they generate progeny of more than one phenotype. We have begun to address this question by asking if individual cells of the ventricular zone generate exclusively neurons or glia at the onset of cortical neurogenesis in the rat. To assess the phenotypes of cells derived from a common progenitor cell, retroviral-mediated gene transfer was used to introduce the reporter gene, Escherichia coli beta-galactosidase, into ventricular zone cells at embryonic day 15 or 16. We used histochemistry to reveal beta-galactosidase-expressing cells in the mature rat cerebral cortex. Isolated clusters of beta-galactosidase-expressing cells, presumably clones, were identified in serial sections. Since the histochemical reaction product is electron dense, each cell could be examined at the ultrastructural level and assigned definitively to one of the major classes of cells in the cerebral cortex on the basis of well-established morphological criteria. This approach overcomes the problems of cell type identification encountered with light microscopy, where it is not always possible to distinguish between different cell phenotypes. We found that virtually all clones contained cells of exclusively one type: either all astrocytes, all oligodendrocytes, or all neurons. Furthermore, each particular cell type exhibited a different pattern and intensity of staining. The neuronal clones, with one exception, were composed of either all pyramidal cells (projection neurons), or all nonpyramidal cells (interneurons). The size and composition of neuronal clones did not seem related to their position in the cerebral cortex. Collectively, our observations indicate that separate progenitor cells exist for pyramidal neurons, nonpyramidal neurons, astrocytes, and oligodendrocytes. The striking phenotypic homogeneity in the clones arising from individual progenitor cells suggests that by the onset of cortical neurogenesis, at least some lineage restrictions have already occurred among the precursor cell population. Thus, our results suggest that lineage may play a pivotal role in determining some of the functionally important phenotypic attributes of cells in the cerebral cortex. PMID- 8463849 TI - Extended temporal gradient for the retrograde and anterograde amnesia produced by ibotenate entorhinal cortex lesions in mice. AB - Effects of ibotenic entorhinal cortex (EC) lesions on both retrograde and anterograde amnesia in mice were assessed using two-choice discrimination tasks learned at different intervals before surgery in two eight-arm radial mazes. The results indicated that EC-lesioned mice were severely impaired in postoperative retention of discrimination problems learned 3 d or 2 weeks prior to surgery, but showed no deficit on problems learned between 4, and up to 6 weeks before surgery, as compared to sham-operated controls. When trained on a novel two choice discrimination problem (not acquired preoperatively), experimental subjects demonstrated quite normal rates of acquisition, but were impaired in learning its reversal. Furthermore, they exhibited a faster rate of forgetting (anterograde amnesia) relative to controls over a 2-week retention interval. These results indicate that approximately 4 weeks is required before memory for a two-choice spatial discrimination problem no longer depends on the integrity of the entorhinal cortex, and suggests that, beyond this time, an EC-independent memory storage system is capable of supporting the retrieval of information. The data, together with complementary behavioral results, are discussed in the context of current theories of memory storage. PMID- 8463850 TI - The behavioral repertoire of the gastric mill in the crab, Cancer pagurus: an in situ endoscopic and electrophysiological examination. AB - Simultaneous endoscopic and electrophysiological recordings were used to observe the behavior of the gastric mill complex while recording the motor output of the stomatogastric ganglion (STG) in intact crabs. In the crab STG, many pattern generating neurons are able to fire in several distinct rhythmic motor patterns. Specifically, many neurons can switch between firing in time with the rapid pyloric rhythm to firing in time with the slower gastric mill rhythm (Weimann et al., 1991). We now correlate behaviorally relevant movements of the gastric mill with some of the modifications of neuronal firing patterns previously characterized using in vitro STG preparations. The intracellular and extracellular recordings from the intact crab are largely indistinguishable from those obtained from in vitro preparations. For the first time, we describe the movements that result as neurons switch their activity patterns associated with activation of the gastric mill rhythm. Extracellular stimulation and intracellular depolarization of individual motor neurons is used to determine the relationship between frequency of firing and movement in behaving animals. PMID- 8463851 TI - Oral arginine supplementation does not affect lymphocyte proliferation during endotoxin-induced inflammation in rats. AB - Earlier studies from this laboratory were unable to confirm reported immunostimulatory effects of supplemental dietary arginine on healthy, unstressed young or aged rats. The present study was undertaken to determine effects of oral arginine supplementation on in vitro measures of immune function using a stressed rat model. The stressor used was intraperitoneal injection of bacterial lipopolysaccharide (1 mg/kg body wt). Four-month-old male Sprague-Dawley rats were placed in either a control or an arginine-supplemented (7.5 g/L arginine-HCl in drinking water) group for 7 d, after which control and supplemented rats received injections of endotoxin or phosphate-buffered saline. Rats were killed 3 d following injections. Endotoxin treatment resulted in lower food intake, less thymic cellularity and greater splenic weight. Endotoxin injections also enhanced proliferative response of rat splenocytes to pokeweed mitogen (1 mg/L) and lipopolysaccharide (25 and 100 mg/L) and enhanced response of thymocytes to concanavalin A (10 mg/L), phytohemagglutinin (25 and 100 mg/L) and pokeweed mitogen (1 mg/L). Supplemental arginine did not reduce thymic weight loss or influence mononuclear cell proliferation or interleukin-2 production in the presence or absence of endotoxin stress. These data indicate no benefit of arginine supplementation during endotoxin stress in rats. PMID- 8463852 TI - A diet history questionnaire ranks nutrient intakes in middle-aged and older men and women similarly to multiple food records. AB - We evaluated the reproducibility of a modified version of the National Cancer Institute diet history questionnaire and also studied comparability of nutrient estimates from this questionnaire to those from four 2-d food records. Subjects (n = 211) were from a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study in south-central Wisconsin. Median age specific correlation coefficients between the questionnaire, administered twice at a 3-mo interval, were 0.8 in men and 0.7 in women (range = 0.5 to 0.9). Questionnaire estimates of protein, cholesterol, thiamin, niacin, iron and zinc were consistently lower than food record estimates whereas estimates of fat were higher. Correlation coefficients between estimates from the questionnaire and records were generally > 0.5, indicating overall good agreement in ranking. However, the range in correlation coefficients was wide [ranging from 0.06 for iron (without supplements) in middle-aged women to 0.8 for alcohol in middle-aged men and women]. Questionnaire estimates similarly classified persons into the lowest two food record quintiles of intake 50 to 93% of the time depending on nutrient. These results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records. PMID- 8463853 TI - Regulation of intestinal nutrient transport is impaired in aged mice. AB - To determine the effect of age on the regulation of intestinal nutrient absorption, we fed young (7.6-mo-old) and aged (24.8-mo-old) C57BL mice diets designed to stimulate in vitro sugar or amino acid uptake in the isolated small intestine. In each age group, diet had no effect on feeding rates and body weights. D-Glucose and D-fructose uptakes by the small intestine each increased by about two times in young and 1.5 times in aged mice fed high carbohydrate diets as compared with those fed no carbohydrate. Adaptive increases in uptake by the aged group were not only reduced but also restricted to more proximal regions of the small intestine. In both age groups, diet-stimulated increases in D glucose transport were accompanied by parallel increases in number of Na(+)-D glucose cotransporters as estimated by specific phlorizin binding. Diet had no effect on transporter Kd for phlorizin, turnover rate of each transporter, mucosal mass or mucosal permeability. A high protein diet stimulated the uptake of L-aspartate and L-proline in young mice and of only L-aspartate in aged mice. Uptake of essential amino acids and of nonessential amino acids sharing transporters with essential ones were not regulated. Although aged mice possess adaptive mechanisms to diet that are similar to those in young mice, the effectiveness of these mechanisms may be impaired with age and may result in malabsorption symptoms so prevalent in the elderly. PMID- 8463855 TI - Bioavailable level and source of cysteine determine protein quality of a commercial enteral product: adequacy of tryptophan but deficiency of cysteine for rats fed an enteral product prepared fresh or stored beyond shelf life. AB - Young rats were used in bioassays designed to assess the protein quality and tryptophan as well as cystine adequacy of the enteral product TwoCal-HN that was either freshly prepared or had been stored (nonrefrigerated) in a warehouse for 10 mo (i.e., beyond shelf life). Based upon supplementation studies, cystine was observed to be the first-limiting amino acid in both fresh and expired TwoCal-HN, and tryptophan was not second limiting. Protein efficiency ratio (PER) of expired, but not fresh, TwoCal-HN was lower than that of the casein control diet, but with cystine supplementation, PER of the TwoCal-HN products was equal to or greater than the PER of the casein control. With a diet containing 10 g protein/100 g that also contained energy-furnishing ingredients simulating TwoCal HN, maximal growth enhancement occurred with a supplement of 1 g cystine/kg diet. Both glutathione and N-acetyl-L-cysteine were observed to be equivalent to an isomolar level of L-cystine in stimulating growth. Using a chemically defined amino acid diet that was singly deficient in tryptophan, bioavailability of tryptophan was determined for casein, fresh TwoCal-HN, expired TwoCal-HN and D tryptophan. Slope-ratio bioefficacy values relative to L-tryptophan (weight gain regressed on supplemental tryptophan intake) indicated that none of the experimental sources of tryptophan had bioavailabilities different from 100%. The results indicated that tryptophan did not deteriorate, as measured analytically or biologically, as a result of storing TwoCal-HN beyond shelf life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463854 TI - Dietary lipid profile is a determinant of tissue phospholipid fatty acid composition and rate of weight gain in rats. AB - Modifications in membrane fatty acid composition and insulin action are possible through dietary intervention. We examined the metabolic fate of (n-3) fatty acids in male Wistar rats, using three isocaloric, high fat diets. The ET-L, OL-L and SAF-L diets contained edible tallow, olive oil and safflower oil, respectively, with identical amounts of (n-3) fatty acids as linseed oil. Despite isocaloric feeding, weight gain was lower (P < 0.001) in rats fed the more highly saturated ET-L diet (69 +/- 8 g) than in those fed either the high (n-9) fatty acid OL-L diet (93 +/- 2 g) or the high (n-6) fatty acid SAF-L diet (108 +/- 4 g). Analysis of red quadricep fatty acid composition revealed phospholipid (n-3) fatty acid levels in the ET-L-fed group (21.6 +/- 0.8 g/100 g fatty acids) to be significantly higher than in either the OL-L-fed (17.7 +/- 0.6 g/100 g fatty acids, P < 0.05) or SAF-L-fed (15.3 +/- 0.7 g/100 g fatty acids, P < 0.05) group. A similar pattern was observed in other muscles and white adipose tissue. A follow-up study using 14C-labeled (n-3) fatty acids in the diet showed greater (n 3) fatty acid incorporation in the ET-L-fed group relative to the other two groups and conversely lower 14CO2 production than in the SAF-L-fed group. These results demonstrate that metabolic fate of dietary fatty acids is strongly influenced by the overall fatty acid profile of the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463856 TI - Genetically determined body weight loss in mice fed diets containing salmon oil. AB - Several reports describe adverse effects of dietary fish oil. We examined the influence of dietary salmon oil (138 g/kg diet) fed without or with 5 g supplemental cholesterol/kg diet on body weight and plasma lipid concentrations of inbred mice. Salmon oil contained 0.17 g naturally occurring cholesterol/kg diet. Mice used were BALB/c, C57BL/6 and seven recombinant inbred strains derived from BALB/c and C57BL/6 (CXB). Parental strains BALB/c and C57BL/6 maintained or gained body weight when fed both salmon oil diets. Mice of recombinant inbred strains showed weight gain except for CXB-E and -H mice. Although CXB-E mice lost approximately 12% of initial body weight after 10 d of consuming either salmon oil diet, no further reductions in body weight were seen. CXB-H mice maintained or gained weight when fed the salmon oil-high cholesterol diet but showed a steady decline in body weight (up to 30% of initial weight) while consuming the salmon oil-low cholesterol diet. The biochemical basis for weight loss in CXB-H mice was studied and results suggest effects of diet on satiety and/or lipid utilization. Because nonparental body weight phenotypes were observed among recombinant inbred strains, body weight response to salmon oil feeding is controlled by multiple genes. PMID- 8463857 TI - High dietary calcium level decreases colonic phytate degradation in pigs fed a rapeseed diet. AB - The degradation of phytate (inositol hexaphosphate) in rapeseed meal diet not containing phytase activity was studied in 15 growing ileum-fistulated pigs. Stomach and small intestinal degradation and total gastrointestinal degradation were compared. The effect of addition of calcium carbonate to the rapeseed meal diet at two levels (9.2 and 18.5 g/kg diet) was investigated. A commercial barley wheat-soybean diet with intrinsic phytase activity was used as reference. Phytate and its hydrolysis products in diets, ileal digesta and feces were determined by HPLC ion-pair chromatography. Hydrolysis of phytate in the stomach and small intestine was 35-45% in pigs fed the rapeseed meal diet independent of calcium addition, and 65% in pigs fed the reference diet. Total gastrointestinal degradation of phytate in pigs fed the rapeseed diet was 97, 77 and 42% (P < 0.001) when calcium intakes were 4.5, 9.9 and 15 g/d, respectively; total gastrointestinal degradation was 72% in pigs fed the reference diet. The intestinal phytate degradation pattern, when rapeseed diet was fed, indicated the activity of an unspecific phosphatase, whereas that of the reference diet indicated intrinsic dietary phytase activity. We conclude that dietary supplementation of calcium carbonate decreases the phytate degradation in the colon of pigs, but not in the stomach and small intestine. PMID- 8463858 TI - Cytotoxicity of fecal water is dependent on the type of dietary fat and is reduced by supplemental calcium phosphate in rats. AB - The effects of the type of dietary fat (180 g/kg diet) and of calcium phosphate (CaHPO4) supplementation (25 vs. 225 mmol/kg diet) on luminal solubility of fatty acids and bile acids, cytotoxicity of fecal water and intestinal epitheliolysis were studied in rats. In rats fed the low and high calcium phosphate diets, fecal excretion of fatty acids diminished in the order palm oil > milk fat > corn oil. Palm oil also caused the highest concentration of fatty acids measured in fecal water followed by milk fat and corn oil when fed at both calcium phosphate levels. The differences in concentrations of luminal surfactants in fecal water of rats fed the three fat diets resulted in a fat type-dependent cytotoxicity of fecal water, with that of palm oil-fed rats the most cytotoxic. The concentrations of fatty acids as well as bile acids in fecal water were, however, significantly lowered by calcium phosphate supplementation in rats fed all types of dietary fat. This reduction in concentration of fecal water surfactants resulted in a lower cytotoxicity of fecal water. The concentration of surfactants in fecal water and cytotoxicity were correlated by multiple regression analysis (R = 0.89). Intestinal epitheliolysis measured as alkaline phosphatase activity in fecal water was lowered comparably to the reduction in cytotoxicity by supplemental calcium phosphate. Intestinal epitheliolysis and cytotoxicity of fecal water were correlated (r = 0.92, P < 0.001). The type of dietary fat and the amount of dietary calcium phosphate influence the concentrations of surfactants in fecal water and consequently affect cytotoxicity of fecal water and intestinal epitheliolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463860 TI - Comment on the paper by Perry et al. (1992): hemoglobin differences between blacks and whites. PMID- 8463859 TI - Colostrum protein digestion in newborn lambs. AB - The efficiency of colostral protein digestion was studied in nine newborn lambs fed one meal of bovine colostrum 3 h after birth. The results were compared with those obtained in two unfed lambs and four lambs fed bovine milk. The protein and peptide composition [immunoglobulins G1 and (IgG1), beta-lactoglobulin, alpha lactalbumin, caseins and peptides resulting from casein hydrolysis] of digesta, gastrointestinal tissues, blood and urine were determined in samples taken 0.75 or 4 h after feeding. The amounts of ingested proteins in lambs fed colostrum were much higher than in those fed the milk diet, and their abomasal emptying was faster. alpha-Lactalbumin was highly degraded by abomasal and intestinal proteases, whereas beta-lactoglobulin and in particular the immunoglobulins were less sensitive. The gastric emptying of caseins was delayed in and the kinetics of appearance of peptides originating from casein hydrolysis was comparable to that observed in lambs fed milk and in 1-mo-old preruminant calves. Thirty-five percent of dietary amino acids ingested as colostrum were available within 4 h for amino acid metabolism; this percentage was 54% in the milk-fed lambs. In the lambs fed colostrum, these amino acids were provided by beta-lactoglobulin, casein and IgG1 (0.52, 0.43 and 0.30 g/kg body wt, respectively), whereas in milk fed animals casein and beta-lactoglobulin were the most important sources of these amino acids (0.40 and 0.20 g/kg, respectively). PMID- 8463861 TI - E. Neige Todhunter (1901-1991). PMID- 8463862 TI - Neural mechanisms in the responses to amino acid deficiency. AB - Food intake is rapidly and reliably reduced when animals are offered diets that result in an essential amino acid deficiency, such as those used in the imbalanced amino acid diet (IMB) paradigm. There seem to be at least three phases in the responses of rats to IMB: 1) In order to respond to a dietary challenge, the animals must first recognize that challenge. The available data suggest that before the behavioral effects occur, a decline in the concentration of an essential amino acid is sensed in a specific brain area, the prepyriform cortex. This recognition phase is associated with localized decreases in the concentrations of the limiting amino acid, norepinephrine and cyclic AMP and with altered protein synthesis. 2) Subsequent to recognition of the deficiency, a conditioned taste aversion develops, mediated in part by serotonin at the level of the vagus. 3) Finally, in the absence of a choice, the animals adapt to an IMB (but not a diet devoid of one or more essential amino acids) in approximately 1 wk. Damage to certain extrahypothalamic brain areas or liver denervation accelerates adaptation to IMB, suggesting both central and peripheral control in the adaptation phase. The resulting behavioral responses provide adaptive advantage to an animal in the selection of a diet with an appropriate balance of amino acids. PMID- 8463863 TI - Chromium in human nutrition: a review. AB - This review summarizes the results of 15 controlled studies supplementing defined Cr(III) compounds to subjects with impaired glucose tolerance. Three of these (3 4 mumol Cr/d for > 2 mo) produced no beneficial effects: serum glucose, insulin and lipid concentrations remained unchanged. The remaining 12 interventions improved the efficiency of insulin or the blood lipid profile of subjects (ranging from malnourished children and healthy middle-aged individuals to insulin-requiring diabetics). In addition, three cases of impaired glucose tolerance after long-term total parenteral alimentation responding to Cr supplementation have been reported. Chromium potentiates the action of insulin in vitro and in vivo; maximal in vitro activity requires a special chemical form, termed Glucose Tolerance Factor and tentatively identified as a Cr-nicotinic acid complex. Its complete structural identification is a major challenge to chromium research. The development and validation of a procedure to diagnose chromium status is the second challenge. Such a test would allow the assessment of incidence and severity of deficiency in the population and the selection of deficiency in the population and the selection of chromium-responsive individuals. The third challenge is the definition of chromium's mode of action on parameters of lipid metabolism that have been reported from some studies but not others. Future research along these lines might establish whether chromium deficiency is a factor in the much discussed "Syndrome X" of insulin resistance. PMID- 8463864 TI - Vitamin A is involved in maintenance of epithelial cells on the bronchioles and cells in the alveoli of rats. AB - We examined the effects of mild vitamin A deficiency and ozone (O3) exposure on the labeling index, a marker of cell proliferation, of epithelial cells on the bronchiole and cells in the alveoli of rat lungs, to assess the role of vitamin A in maintenance of epithelial cells on the distal airway and alveolus. Three-week old rats were fed a vitamin A-depleted diet for 4 wk to induce mild vitamin A deficiency. After 2 wk rats were exposed to 16.4 mumol O3/m3 for 1 to 14 d. In vitamin A-sufficient rats, labeling indices of epithelial cells on the bronchiole and cells in the alveolus increased significantly in comparison with those of controls exposed to clean air on d 2 and 3 of O3 exposure. In vitamin A-deficient rats as well, labeling indices were increased by O3 exposure, but the magnitude of increase was significantly smaller than for vitamin A-sufficient rats. These results indicate that vitamin A deficiency resulted in decrease of proliferation of epithelial cells on the distal airway and cells in the alveolus of rats when the proliferation of these cells was stimulated by O3 exposure, suggesting an involvement of vitamin A in maintenance of lung epithelial cells. PMID- 8463865 TI - Metallothionein expression in rat bone marrow is dependent on dietary zinc but not dependent on interleukin-1 or interleukin-6. AB - The comparative influence of dietary zinc status and recombinant human interleukin-1 alpha (rhIL-1 alpha) and recombinant human interleukin-6 (rhIL-6) on metallothionein (MT) gene expression was examined in rat bone marrow and liver. Growing male rats were fed a diet with 5 (restricted), 30 (control), or 180 (supplemented) mg Zn/kg for 14 d. On d 15, rats were injected with 5 micrograms of rhIL-1 alpha or rhIL-6. Marrow metallothionein responded directly to dietary zinc but did not respond to these cytokines. Significantly less zinc accumulated in marrow from the zinc-restricted rats compared with control or supplemented rats. Analysis of metallothionein isoform mRNA expression showed MT 1 is the primary gene expressed in marrow. A significant interaction between dietary zinc and cytokine treatment was observed in the liver. Hepatic metallothionein induction following both rhIL-1 alpha and rhIL-6 injection was directly related to dietary zinc intake. Expression of hepatic metallothionein isoform mRNAs suggested MT-1 responded to zinc and MT-2 responded to cytokines. These results indicate that metallothionein gene expression in both the marrow and the liver responds to dietary zinc status. In contrast, liver metallothionein expression can be altered by these cytokines, which are known to act on many cell types. Furthermore, these results suggest that bone marrow metallothionein could be of importance in the development of marrow cells. PMID- 8463866 TI - Weight gain of Kenyan school children infected with hookworm, Trichuris trichiura and Ascaris lumbricoides is improved following once- or twice-yearly treatment with albendazole. AB - We studied growth in infected children given one dose (600 mg) or two doses of albendazole per school year. Children were examined and allocated at random within sex by descending hookworm egg count to one of three groups: placebo (n = 93), one dose (1x, n = 96) or two doses (2x, n = 95). Each child was treated and then re-examined and treated 3.6 and 8.2 mo later (Exams 2 and 3). The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight (1.1 and 0.9 kg more, respectively), percent weight-for-age (3.3 and 2.7 percentage points more), percent weight-for-height (3.1 and 2.9 percentage points more), percent arm circumference-for-age (2.3 and 2.0 percentage points more) and triceps and subscapular skinfolds but did not differ significantly from each other. The placebo group showed significant decreases between exams (P < 0.0002) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height, whereas the 1x and 2x groups exhibited significant increases (P < 0.005). At Exam 3, arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95% for hookworm, 42 and 32% for Trichuris and 55 and 87% for Ascaris, respectively. We conclude that one or two doses of albendazole per year resulted in similar growth improvements, despite reinfection, in school age children in an area where these helminths and poor growth are prevalent. PMID- 8463867 TI - High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. AB - For regions where vitamin A deficiency is common, high dose vitamin A supplementation of lactating mothers is currently recommended, but the effects of this intervention have not been carefully evaluated. We conducted a randomized, double-blind trial in which 153 Indonesian mothers 1-3 wk postpartum received either a capsule containing 312 mumol of vitamin A as retinyl palmitate or a placebo. Mothers' serum retinol concentrations in the vitamin A group tended to be lower than in the placebo group at baseline but higher at 3 mo postpartum (1.39 vs. 1.24 mumol/L, P = 0.03) and 6 mo postpartum (1.23 vs. 1.08 mumol/L, P < 0.01). The milk retinol concentrations of the vitamin A group were higher than those of the placebo group by 0.48 to 1.18 mumol/L at 1-8 mo postpartum (P < 0.05). Among the infants at 6 mo of age, the prevalences of low serum retinol concentration (< 0.52 mumol/L) were 36 and 15% in the placebo and vitamin A groups, respectively (P < 0.005), and the prevalences of low vitamin A stores (assessed by relative dose response) were 23 and 10%, respectively (P < 0.03). High dose vitamin A supplementation of lactating mothers is an efficacious way to improve the vitamin A status of both mother and breast-fed infant. PMID- 8463868 TI - Fate of beta-cyclodextrin in the human intestine. AB - We assessed the fate of beta-cyclodextrin, which is composed of seven alpha(1- >4)-linked glucose units in ring structure, in the human gastrointestinal tract. In four healthy ileostomists, ileal effluent was collected after oral administration of beta-cyclodextrin during fasting (10 g of beta-cyclodextrin) and postprandially (10 g of beta-cyclodextrin three times daily with meals). In 10 healthy volunteers, the amount of beta-cyclodextrin passing into the colon was determined by means of the breath hydrogen technique using lactulose as a standard, and stools were collected after oral administration of beta cyclodextrin during fasting (10 g of beta-cyclodextrin) and postprandially (10 g of beta-cyclodextrin three times daily with meals). In ileostomists, we recovered from the small intestine 91 +/- 5% and 97 +/- 10% (mean +/- SD) of beta cyclodextrin ingested during fasting and with meals, respectively. In healthy volunteers, H2 excretion in breath after beta-cyclodextrin ingestion was low compared with excretion after lactulose, but only traces of beta-cyclodextrin were recovered in stools. We conclude that beta-cyclodextrin is poorly hydrolyzed in the human small intestine but that it is fermented by the colonic flora with apparent minimal H2 production. PMID- 8463869 TI - Interaction between methane-producing status and diet on serum acetate concentration in humans. AB - About half the population excretes methane in the breath. To see if methane producing status influenced serum acetate, we studied six methane producers and six nonproducers on three separate days. For 36 h they ate a polysaccharide-free diet alone, or with 20 g of unabsorbed sugar lactulose, or 20 g of fermentable fiber, guar, in random order. The mean fasting serum acetate concentration on the three test days in producers was higher than in nonproducers, 84 +/- 5 vs. 69 +/- 5 mumol/L (P < 0.05). Compared to the control diet, both lactulose and guar raised serum acetate concentration significantly in both groups of subjects. However, there was a significant interaction between methane producing status and diet. After lactulose consumption, postprandial serum acetate was similar in both groups of subjects, but guar consumption had a significantly greater effect in producers than nonproducers (98 +/- 8 vs. 73 +/- 5 mumol/L; P < 0.05). We conclude that methane producing status may influence serum acetate concentrations in humans, depending upon the type of fermentable carbohydrate in the diet. PMID- 8463870 TI - Synthesis of [75Se]selenoproteins is greater in selenium-deficient sheep. AB - Three Se-deficient and three Se-sufficient sheep with mean erythrocyte glutathione peroxidase activities of 30 and 249 mumol NADPH oxidized.min-1.g hemoglobin-1, respectively, were each labeled intraperitoneally with 555 MBq of sodium [75Se]selenite. All animals were killed and necropsied after 7 d. Peak plasma radioactivity occurred from 1 to 3 h post-labeling. Radioactivity in plasma associated with [75Se]selenoproteins was significantly higher in the Se deficient sheep than in the Se-sufficient sheep 3 and 6 d after isotope administration. SDS-PAGE analysis of plasma followed by autoradiography indicated five selenoproteins, all of which were present in both groups. The molecular weights were 21.0, 23.0, 48.0, 55.5 and > 100 kDa. The protein with a mass of 55.5 kDa accounted for > 40% of the total radioactivity in both groups of sheep. Nine selenoproteins with molecular weights of 15.7, 18.8, 22.9, 26.8, 37.3, 42.4, 56.1, 62.7 and 71.3 kDa were detected in extracts from a range of tissues. Liver, kidney, heart and pituitary retained more radioactivity than the other tissues examined and the total amount of protein-associated 75Se in the liver, kidney and pituitary of Se-deficient sheep was significantly greater than that in Se sufficient controls. PMID- 8463871 TI - Dietary cholesterol-induced down-regulation of intestinal 3-hydroxy-3 methylglutaryl coenzyme A reductase activity is diminished in rabbits with hyperresponse of serum cholesterol to dietary cholesterol. AB - Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was twofold higher in the hyporesponders. The addition of cholesterol (3 g/kg) to the diet caused similar depression of hepatic HMG-CoA reductase activity in the two strains, whereas intestinal HMG-CoA reductase activity was significantly reduced in hyporesponders but not in hyperresponders. Cholesterol feeding induced higher free cholesterol concentrations in hepatic and intestinal microsomes of both hypo and hyperresponders and higher activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). Hepatic ACAT activity was significantly lower in cholesterol-fed hyperresponders than in hyporesponders, which may have contributed to the observed higher free cholesterol concentrations in hepatic microsomes of cholesterol-fed hyperresponders. Intestinal ACAT activity was similar in hypo- and hyperresponders; cholesterol feeding tended (P = 0.11) to elevate the activity of this enzyme. Hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in cholesterol-fed hyperresponders than in hyporesponders; it was slightly depressed after cholesterol loading in both rabbit strains. PMID- 8463872 TI - Rats fed high starch diets have lower colonic proliferation and fecal bile acids than high sucrose-fed controls. AB - We studied the effects of sucrose or starch in the diet (460 g/kg diet) on fecal bile acid concentrations in Sprague Dawley rats after 4 wk of feeding. Total bile acid concentration in the feces was significantly lower in the rats fed the starch diet than in those fed the sucrose diet (4.56 +/- 0.47 mg/g dry weight and 8.03 +/- 0.94, respectively, SEM), due to a reduction of deoxycholic, alpha muricholic and beta-muricholic acids. Fecal and cecal pH values were significantly lower in the rats fed the starch diet compared to those fed the sucrose diet (6.79 +/- 0.08 and 7.15 +/- 0.09 for fecal pH and 7.02 +/- 0.05 and 7.2 +/- 0.04 for cecal pH in the two diet groups, respectively). Colon proliferation was also significantly lower in the starch-fed rats compared to those fed sucrose (labeling index 3.51 +/- 0.6 and 5.69 +/- 0.74, respectively), and the reduction was apparent in the middle and upper compartments of the colon crypts. The mucosal proliferation, expressed as percentage of labeled cells in the upper compartment of the colon crypts, was positively correlated with the concentration of deoxycholic, lithocholic, alpha-muricholic, beta-muricholic, cholic and total bile acids in the feces (per gram wet weight). The results indicate a protective effect of starch versus sucrose diets on colon mucosa. PMID- 8463873 TI - [3H]phytic acid (inositol hexaphosphate) is absorbed and distributed to various tissues in rats. AB - To understand the mechanism of antineoplastic action of phytic acid, we investigated the absorption and distribution of myo-[inositol-2-3H(N)] hexakisphosphate in rats. The radioactivity was measured in urine, feces, blood, gastrointestinal tract contents and various organs and tissues at 1 and 24 h after intragastric administration. Of the total radioactivity, 79.0 +/- 10.0% was absorbed and at least 26.6% was degraded during the 24-h period following ingestion. The absorption was rapid; 11.0 +/- 2.6% of the radioactivity was detected in the wall of the stomach (4.4 +/- 3.7%) and upper small intestine (6.6 +/- 1.9%), 6.5 +/- 2.6% in the skeletal muscle and 4.0 +/- 1.5% in the skin after 1 h. Much of the radioactivity after 24 h was in the liver (4.0 +/- 0.9%), kidneys (2.2 +/- 1.1%), muscle (18.1 +/- 3.4%) and skin (10.1 +/- 3.3%). Analysis of plasma and urine demonstrated that most of the radioactivity was due to myo inositol and small amounts of inositol monophosphate (InsP1). Gastric epithelial cells, however, contained inositol and various inositol phosphates (InsP1-6). Our data suggest that soluble InsP6 when administered in drinking water is rapidly absorbed through the stomach and upper small intestine, becomes quickly dephosphorylated within the mucosal cells and is distributed to various organs as inositol and InsP1. PMID- 8463874 TI - Nutritional control of fatty acid esterification in differentiating Caco-2 intestinal cells is mediated by cellular diacylglycerol concentrations. AB - The Caco-2 human intestinal cell line was used to investigate the effects of exogenous lipid on fatty acid esterification in differentiating intestinal absorptive cells. Preincubation of Caco-2 cells with either palmitate or palmitate plus 2-monoolein resulted in greater utilization of subsequently added fatty acid for triacylglycerol relative to phosphatidylcholine synthesis. Despite this lipid-induced alteration in metabolism, the activities of acyl-CoA synthetase, glycerol-3-phosphate acyltransferase and diacylglycerol acyltransferase were unchanged. In addition, monoacylglycerol acyltransferase activity was nearly undetectable, even after preincubation with 2-monoolein. The intracellular diacylglycerol concentrations were, however, increased with greater lipid substrate availability. These studies indicate that, under conditions of increased dietary lipid, intestinal fatty acid esterification via the glycerol-3 phosphate pathway is modulated by cellular diacylglycerol concentrations. PMID- 8463875 TI - Menadione nicotinamide bisulfite is a bioactive source of vitamin K and niacin activity for chicks. AB - Young chicks were fed a vitamin K-deficient soybean concentrate basal diet containing graded levels of menadione from menadione nicotinamide bisulfite (MNB) or menadione dimethyl-pyrimidinol bisulfite (MPB) to assess prothrombin time as a function of menadione intake. Prothrombin time decreased linearly as menadione dose increased from 0 to 400 micrograms/kg. Multiple linear regression slope ratio calculations indicated that both sources of menadione were of equal potency. To assess niacin bioactivity of MNB, graded doses of nicotinamide (0 to 5 mg/kg) from MNB or nicotinamide were added to a niacin-deficient diet based upon corn, corn gluten meal and vitamin-free casein. Weight gain increased linearly as a function of nicotinamide dose, and multiple linear regression analysis of weight gain as a function of supplemental nicotinamide intake revealed no significant differences in slope between the two sources of nicotinamide. Using excess doses, MNB was compared with MPB in acute (single crop intubation) or chronic (fed in the diet for 14 d) toxicity trials. With a single menadione dose of 1600 mg/kg body wt, weight gain in the subsequent 14-d period was reduced by MNB but not by MPB. Mortality rates of 25 and 17% occurred for MPB and MNB, respectively, at this dose level. Doses lower than 1600 mg/kg body wt caused neither morbidity nor mortality. When provided in the diet for a 14-d feeding period, menadione doses of 3000 mg/kg diet from MNB reduced gain, feed intake, gain:feed ratio and blood hemoglobin concentration. Menadione doses of 6000 mg/kg diet were required to produce morbidity of this type when MPB was fed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463876 TI - Requirement of hybrid striped bass for dietary (n-3) highly unsaturated fatty acids. AB - A feeding trial was conducted to quantify the requirement of hybrid striped bass (Morone chrysops female x M. saxatilis male) for dietary (n-3) highly unsaturated fatty acids (HUFA), specifically eicosapentaenoic [20:5(n-3)] and docosahexaenoic [22:6(n-3)] acids. Graded levels of (n-3) HUFA as ethyl esters were substituted for part or all of the 5 g olive oil/100 g diet in the semipurified basal diet. Total amount of 20:5(n-3) plus 22:6(n-3) in the experimental diets was 0.5, 1.1, 1.5, 2.0 or 3.2 g/100 g dry wt. Control fish received a diet containing menhaden fish oil at 5 g/100 g. Each diet was fed to triplicate groups of hybrids (with an initial average weight of 13.0 g/fish) in aquaria for 10 wk. Significantly (P < 0.05) higher relative weight gain as well as more efficient food and protein utilization were observed for fish fed the diets with 0.5, 1.1, 1.5 or 2.0% (n-3) HUFA or 5% menhaden fish oil as compared with those fed the basal diet. These responses generally reached a plateau between 1.1 and 1.5% (n-3) HUFA, but the lowest values were observed for fish fed the diet with 3.2% (n-3) HUFA. Fatty acid composition of body lipids (total lipid of intraperitoneal fat and polar lipids of muscle and liver) was affected by diet and indicated some elongation and desaturation of octadecatetraenoic acid [18:4(n-3)] and 20:5 (n-3) to 22:6(n 3). These data indicated that 20:5(n-3) and 22:6(n-3) are essential for hybrid striped bass, and the minimum requirement is approximately 1% of diet or 20% of dietary lipid. PMID- 8463877 TI - Long-term phosphorus restriction prevents corticomedullary nephrocalcinosis and sustains reproductive performance but delays bone mineralization in rats. AB - In a long-term experiment with three successive generations of rats, the influence of dietary phosphorus restriction (2 instead of 4 g phosphorus/kg diet) on nephrocalcinosis, reproduction and bone mineralization was studied. Nephrocalcinosis in female rats, as based on kidney calcium concentration and histological examination, was prevented by phosphorus restriction. The low phosphorus diet caused reduced femur concentrations of magnesium, calcium and phosphorus in rats of the first and second generation aged 4 to 12 wk. The low phosphorus diet resulted in lower plasma phosphorus concentrations. In the kidneys of female rats, immediately after lactation, a higher degree of tubular hyperplasia was seen after the low phosphorus diet was fed. Reproductive performance was not affected by phosphorus restriction. We conclude that 0.2% phosphorus in the diet prevents nephrocalcinosis in female rats while it sustains reproduction but delays bone mineralization. PMID- 8463878 TI - 1,25-dihydroxycholecalciferol supplementation prevents hypocalcemia in magnesium deficient chicks. AB - To determine the relevance of circulating 1,25-dihydroxycholecalciferol [1,25(OH)2D3] to the pathogenesis of hypocalcemia during magnesium deficiency, growing chicks were pair fed control or Mg-deficient diets with or without 1,25(OH)2D3 supplementation. Within 14 d, chicks fed the Mg-deficient diet without 1,25(OH)2D3 supplementation exhibited hypomagnesemia and hypocalcemia compared to control chicks. 1,25-Dihydroxycholecalciferol supplementation in Mg deficient chicks elevated plasma 1,25(OH)2D3 twofold and increased plasma calcium to control levels. Supplementation with 1,25(OH)2D3 did not increase plasma Mg concentration in Mg-deficient chicks, indicating that exogenous 1,25(OH)2D3 prevented hypocalcemia in the absence of greater Mg availability. Magnesium deficient chicks supplemented with 1,25(OH)2D3 had more intestinal calbindin D 28K relative to Mg-deficient nonsupplemented chicks, suggesting that increased absorption of dietary Ca may have contributed to the greater plasma Ca concentration in 1,25(OH)2D3 supplemented Mg-deficient chicks. Although clinical hypomagnesemia has been associated with vitamin D resistance, our data indicate that primary Mg deficiency did not impair target tissue responsiveness to 1,25(OH)2D3, at least at the level of the intestine. Supplementation with 1,25(OH)2D3 did not increase bone Mg concentration and did not alter the characteristic skeletal morphology. It also did not increase bone Ca concentration in Mg-deficient chicks. The data suggest that skeletal alterations during Mg deficiency result from hypomagnesemia per se, rather than hypocalcemia or insufficient 1,25(OH)2D3. PMID- 8463879 TI - Coordinated strategies for controlling micronutrient malnutrition: a technical workshop. AB - Participants in a November 1991 workshop concluded that coordinated strategies for controlling malnutrition due to iodine, iron, vitamin A and other micronutrients deficiencies are technically feasible and should be given consideration in planning control efforts. Coordinated surveys involving clinical, biochemical and dietary assessment of multiple micronutrients are feasible. Multiple fortification is also possible using such vehicles as salt, processed rice or sugar. Supplementation efforts can be integrated with existing health care programs. Food-based strategies are also effective. The best examples have been community-based and have included a strong nutrition and health education component designed to change food consumption patterns, improve food preservation and preparation practices, and link income-generating activities with food production activities. Successful coordinated efforts will require a strong political commitment and a supportive infrastructure. Specific recommendations include the formation of national coordinating bodies for micronutrient deficiency control, establishment of a micronutrient information network and expansion of technical exchange and training. PMID- 8463880 TI - [Orbital wall fractures: a comparison of computed tomography and conventional views]. AB - A total of 59 cases of mild facial fractures (simple orbital wall fractures, 34 cases, other facial fractures, 25 cases) with the clinical suspects of orbital wall fractures were evaluated both by conventional views (Waters' and Caldwell views) and coronal CT scans. Conventional views were obtained, as an average, after 4 days and CT after 7 days of injuries. Both the medial wall and the floor were evaluated at two sites, i.e., anterior and posterior. The ethmoid-maxillary plate was also included in the study. The degree of fractures was classified as, no fractures, fractures of discontinuity, dislocation and fragmentation. The coronal CT images in bone window condition was used as reference and the findings were compared between conventional views and CT. The correct diagnosis was obtained as follows: orbital floor (anterior, 78%, posterior, 73%), medial orbital wall (anterior, 72%, posterior, 72%) and ethmoid-maxillary plate (64%). The false positive diagnosis was as follows: orbital floor (anterior only, 13%), medial orbital wall (anterior only, 7%) and ethmoid-maxillary plate (11%). The false negative diagnosis was as follows: orbital floor (anterior, 9%, posterior, 10%), medial orbital wall (anterior, 21%, posterior, 28%) and ethmoid-maxillary plate (21%). The results were compared with those of others in the past. PMID- 8463881 TI - [Statistical observations of clinical cases with frontal, ethmoid and sphenoid sinus mucoceles]. AB - Ninety six patients with paranasal mucoceles (or pyoceles) were admitted and treated at Gunma University Hospital from 1977 to 1986 (age range 15-82 years; mean 46.4 years). We statistically investigated these cases paying a special attention to 25 patients with visual disturbance. 1) In 71 cases mucocele was located in the frontal or fronto-ethmoid sinus (FE group), in 12 it was found in the ethmoid sinus (E group), and in 13 it was situated in the sphenoid or spheno ethmoid sinus (SE group). 2) Sixty three cases had histories of previous surgery of paranasal sinuses and 29 cases were considered to have primary mucoceles. 3) The mean age of patients with primary mucocele was 56.4, while that with postoperative mucocele was 41.2. 4) In the FE group recurrence was so frequent that some device for surgical treatment should be considered (i.e., mucous membrane grafting, prolonged insertion of silicon tubes). 5) Visual disturbance was frequently observed in both the E group (7/12) and the SE group (9/13). 6) Visual disturbance may occur when mucocele compress the optic nerve and the globe at retrobulbar portion as well as at the optic canal. Twelve cases out of 25 with visual disturbance belonged in the former type. 7) Optic atrophy was most commonly seen in the SE group, but was recognized in 1 case even in the E group and the FE group respectively. 8) In patients with sudden visual disturbance, if only they were operated within a week after the onset, their visual acuity was remarkably improved except for serious cases. 9) In the cases presented with gradually attacked or varying visual disturbance, there was no correlation between the recovery of the vision and the duration of the disturbance. PMID- 8463882 TI - [Paranasal sinusitis due to Pasteurella multocida]. AB - A case of paranasal sinusitis due to Pasteurella multocida (P. multocida) is reported. A 39-year-old woman presented with chief complaints of rhinorrhea and headache. The patient kept a cat in her house and kept such close contact with it as to wake up by being licked every morning. Bacteriological examination revealed P. multocida isolated from her nasal discharge and also from the saliva of the cat kept by the patient. The two isolates were compatible with respect to biochemical properties, serotype and drug susceptibility. Therefore, P. multocida infection in this case was considered to have originated from the pet cat. P. multocida infection has been increasing recently. One of the reasons is a pet boom. In order to prevent acquiring the infection from a pet animal, we should have knowledge about this infection, advise the patient to avoid close contact with pets, and provide valuable information concerning these problems to society from the viewpoint of zoonosis. PMID- 8463883 TI - [An evaluation of nasal patency with acoustic rhinometry--preop. and postop. comparisons]. AB - Changes in nasal patency after nasal surgeries were evaluated with acoustic rhinometry. Fourteen cases (20 sides) were included in the evaluation and the following types of nasal surgery were performed: 2 partial maxillectomies, 11 Caldwell-Luc operations, 4 endonasal ethmoidectomies, 1 endonasal maxillary sinusectomy and 2 septoplasties. The evaluation with acoustic rhinometry was routinely performed on two occasions; the day before and 7-14 days after the surgery. The preop. and postop. results of the evaluations of nasal volume (6.9 14.1 cm by the area-distance curve) and nasal area (averaged areas at 11.0 cm and 13.4 cm by the area-distance curve) were compared. Postop. results in all but one case demonstrated increases in both nasal volume and nasal area, indicating that acoustic rhinometry has practical applications in preop. and postop. evaluations of nasal patency. Three aspects remain to be clarified. The first is the influence of the nasal cycle, which varies considerably at the time of both preop and postop evaluations. The second is the influence of the paranasal sinuses. When the results of cases who had undergone endonasal ethmoidectomy or septoplasty were compared to those who had received partial maxillectomy or Caldwell-Luc operation, the latter showed greater increases in nasal patency, suggesting that the cavities of paranasal sinuses, especially of the maxillary sinus, influence the results of acoustic rhinometry. The third is the size of the anterior entrance of the middle meatus. When the entrance is narrow, the acoustic pulse generated by acoustic rhinometry will not reach up to the paranasal sinuses so that the size of the entrance will again influence the results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463884 TI - [Effect of methamphetamine on the auditory system]. AB - Four series of experiments were performed to evaluate the effects of methamphetamine on the auditory system of guinea pigs. Methamphetamine was administered to guinea pigs via intraperitoneal injection, and the time course of latencies of waves I, II, III, and IV, interpeak latencies of waves I-III, III IV, and I-IV of the ABR, and the near-field potential of the inferior colliculus and cochlear nerve were measured. These physiological data were analyzed in comparison with the distribution of methamphetamine in the inferior colliculus and cochlea following its immunohistochemical staining, as well as the serum methamphetamine concentration. The following results were obtained; 1. The wave latencies and interpeak latencies of ABR decreased up to 120 minutes after the administration. 2. In the cochlear nerve recording, the amplitude of the response increased and the latency decreased up to 90 minutes after the administration. These changes in responses were, however more prominent in the inferior colliculus recording. 3. Immunohistochemical examination revealed that methamphetamine was present in the hair cells of the organ of Corti, spiral ligament, spiral ganglion cells and the inferior colliculus 30 minutes after the administration. 4. The serum concentration of methamphetamine rapidly reached its maximal level, and then dropped gradually, logarithmically, having become almost horizontal at a low level 6 hours later. These results suggest that methamphetamine does exert an effect on the peripheral auditory system, as well as on the central nervous system, which is generally regarded as the effector organ. It is assumed that the pharmacological effect of methamphetamine on the cochlea involves excitation of sensory cells, afferent nerve fibers and spiral ganglion cells. PMID- 8463885 TI - [Innervation of the external ear in humans and the musk shrew]. AB - The external ear appears only in mammals and possesses a great diversity of forms. In addition, multiple nerves are distributed in the external ear. The nerves which are distributed in the external ear were investigated in humans and in the musk shrew (Suncus murinus) in a macroscopic study. The following results were obtained. Cranial nerves (CN) V, VII, X and cervical nerves supply the auricle and the external meatus in both humans and the musk shrew. Branches of the third division of CN V supply an anterior part of the external meatus and the anterior part of the auricle in both humans and the musk shrew. A branch of CN X, together with a branch of CN VII, supply the posterior parts of the external meatus in humans. In the musk shrew, a branch of CN X, together with a branch of CN VII, supplies the posterior part of the external meatus and the central part and the anterior portion of the auricle. Branches of the cervical nerve supply the posterior part of the auricle. Branches of the cervical nerve supply the posterior part of the external meatus and the central and posterior parts of the auricle in the musk shrew. PMID- 8463886 TI - [Peritonsillar abscess--a comparison of treatment by needle aspiration and incision]. AB - To compare the efficacy of permucosal needle aspiration with that of incision and drainage in the management of peritonsillar abscess, we reviewed the charts of 32 patients, diagnosed as having peritonsillar abscess, who had been admitted to the Central Hospital of Social Health Insurance from June 1987 to December 1991. Twelve patients, 9 males and 3 females, were managed with incision and drainage. Their average age was 34 years, with a range of 23 to 69 years. Permucosal needle aspirations were performed in 20 patients, including 14 males and 6 females. Their age ranged from 16 to 65 with a mean of 36 years. All patients received parenteral antibiotics. The duration of fever over 37.0 degrees C averaged 2.0 hospital days (range, 0 to 8 days) in patients treated with incision and drainage, and 2.1 hospital days (range, 0 to 4 days) in patients treated with needle aspiration. The average postoperative time elapsed until the patient could eat solid food with ease was 3.8 hospital days with a range of 1 to 9 days in patients treated with incision and drainage, and 3.2 hospital days with a range of 1 to 7 days in patients treated with needle aspiration. The hospital stay ranged from 3 to 9 days with an average of 5.4 days in patients treated with incision and drainage, and from 4 to 10 days with an average of 5.5 days in patients treated with needle aspiration. These data indicate that permucosal needle aspiration of peritonsillar abscess provides symptomatic relief and cure which are as rapid as those of incision and drainage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463887 TI - [Computerized database system for pure tone audiometry]. AB - The management and storage of pure tone audiometry data creates a major problem for otolaryngological clinics. We have devised a new computerized database system to overcome this problem. The hardware involved includes multiple audiometers and computers interfaced with a glassfiber local area network (Pi-Net). The software used is database 3 plus, a popular database language and utility software package. Programs were written for data entry, data transfer, reference, entry of patient ID, and evaluation of tympanoplasty. The following benefits of the system are noted. 1) Data entry is possible at every terminal (audiometer and computer). 2) Storage capacity is sufficient for more than 10 years of operation. 3) All data can be retrieved rapidly at any terminal. Evaluations of pre- and post tympanoplasty hearing loss are facilitated by this system. This system is very effective for follow up of hearing disorders. PMID- 8463888 TI - [Consonant sounds processing in 22 channel cochlear implant device and consonant recognition of patients]. AB - This report describes studies on electrode selection of the speech processor of a 22 channel cochlear implant device for 14 Japanese consonants, and on consonant recognition of 23 cochlear implant patients as they relate to electrode selection. The means of electrode selection was studied using a special device capable of detecting code signals delivered from the speech processor for electrode selection. Young male voices consisting of/a/+consonant+/a/ were presented as sound stimuli, and the electrode numbers selected were recorded for each consonant. The recorded numbers were grossly divided into two groups; a higher frequency range of about 500Hz to 4,000Hz and a lower range of 0Hz to about 1,100Hz. They showed characteristic patterns for each consonant, and these electrode number patterns were compared with patterns estimated from a sonogram. Although there were some differences between these two patterns in unvoiced stop consonants, they were roughly parallel to each other in other consonants. The information transfer ratio was calculated based on confusion matrices obtained from test results on 23 patients for 14 consonants. The ratio was high in voicing and semivowels, whereas it was relatively lower in plosives. This seems reasonable on the basis of patterns of electrode number transitions. Nasals and fricatives, however, showed lower information transfer ratios despite adequate electrode selection, and this may due to poorer information transition or the high frequency components of these consonants. PMID- 8463889 TI - [Intravital microscopic and laser Doppler method estimates of cochlear blood flow -effect of transient ischemia on inner ear blood flow]. AB - Cochlear blood flow (CoBF) was measured by intravital microscopy (IVM) and laser Doppler (LD) methods in normal guinea pigs and after a single norepinephrine (NE) injection into the carotid artery. CoBF changed in proportion to BP changes in normal animals. CoBF values by LD correlated well (r = 0.67) with CoBF measured by IVM when BP changed in the 35 and 70 mm Hg range. A linear regression line was obtained as y = 1.407X-2.996. No correlation was found between the diameters of radiating arterioles (RA) and blood volume (i.e., the hemoglobin concentration index). NE injection into the carotid artery induced the formation of sludge at RA, resulting in decreased local CoBF. A decrement in CoBF was also observed by LD after injection. Although similar patterns of CoBF changes were obtained by these two methods after injection, the degree of CoBF change by LD appeared to be lower than that by IVM. Our result indicates that the combination of these two methods provides a better understanding of cochlear circulation. PMID- 8463890 TI - [Effects of head positions on horizontal optokinetic afternystagmus in humans]. AB - In order to study the space orientation of optokinetic afternystagmus in humans, I examined optokinetic afternystagmus in the yaw axis (horizontal OKAN, HOKAN) in both sitting and the 90 degree lateral tilted positions in 29 normal volunteers. Optokinetic stimuli of 80 degree/s were given for 120 seconds using a projection type stimulator. Eye movements were recorded in two dimensions, horizontal and vertical, to the head fixed coordinate axis using conventional electronystagmography. Five parameters of HOKAN (maximum slow phase velocity, time constant of slow phase velocity, total nystagmus number, frequency and duration) in the sitting position were compared with those in the 90 degree lateral positions tilted to the right and to the left. The following results were obtained. 1) OKAN were recorded from all subjects in the sitting position. The mean and the standard deviation of maximal slow phase velocity, duration and the time constant were 11.6 +/- 4.0/s, 35.7 +/- 15.6 seconds and 15.1 +/- 8.5 seconds, respectively. 2) In the lateral positions, the rate of appearance of OKAN decreased to 72%. In the lateral positions, the slow phase velocity decreased to 68% of that in the sitting position. 3) The rate of appearance and the slow phase velocity of OKAN were more active in the direction horizontal to the ground than in the perpendicular direction. These results suggest that otolith input modifies HOKAN in humans. PMID- 8463891 TI - [Distribution of motor nuclei in feline ventral neck muscles]. AB - The distribution of motor nuclei in feline neck muscles at the level of the third and fourth cervical vertebrae of spinal cord was investigated, using retrograde labelling with horseradish peroxidase (HRP). HRP powder was directly injected into the cut ends of the peripheral nerves innervating each muscle. Investigated muscles in this thesis included 5 ventral muscles: Levator scapulae m.(LS), Levator scapulae ventralis m.(LSV), Longus colli m.(LC), Longus capitis m. (LCP), Intertransversarius ventralis m.(ITV). Two dorsal muscles were also examined; Splenius m.(SP) and Biventer m.(BV). The findings in retrogradely labelled motoneurons of each muscle were as follows: 1) LS and LSV (V1 ventral muscles) Labelled motoneurons were observed at the lateral border of the ventral horn, and the distribution of LSV was more dorsal than that of LS. Their cellular distributions varied from the rostral end of the third cervical segment dorsolaterally to the caudal end of the fourth cervical segment ventromedially. 2) LC, LCP and ITV (V2 ventral muscles) Labelled motoneurons were observed at the medial border of the ventral horn. The distribution of LCP was more dorsal than that of LC and ITV, but their cellular distributions were largely intermingled. The variation in cellular distribution, which was observed in V1 ventral muscles, was not recognized in this muscle group. 3) SP and BV (D1 and D2 dorsal muscles) Labelled motoneurons were observed at the apex of the ventral horn, referred to as the ventromedial nucleus by Rexed. The distribution of SP was more dorsolateral than that of BV, and the changes in cellular distribution seen in V1 ventral muscles were also observed in these muscles. Some unorganized labelled cells were found at the medial border of the ipsilateral ventral horn, anterior funiculus, anterior commissure and contralateral ventral horn. These irregularly positioned cells were not found in the staining of the ventral muscles. Organized distributions of motoneurons in the ventral horn corresponded respectively to the classification of trunk muscles, as described by Nishi (1938) in accordance with the peripheral innervation of each trunk muscle. These results indicate that the pattern of peripheral innervation reflects the spinal level, and provides important information for electrophysiological analysis of the neural network between the central and peripheral nervous systems. PMID- 8463892 TI - Pulsed dye laser therapy for port-wine stains in children: psychosocial and ethical issues. AB - The port-wine stain is a disfiguring vascular birthmark that commonly occurs on the face. Amelioration of this condition in children was difficult or impossible until the introduction of the flashlamp-pumped pulsed dye laser in the late 1980s. This article provides an interdisciplinary social and ethical examination of pulsed dye laser therapy for port-wine stain in childhood. Specific issues raised relate to the management of pain during therapy, rationale for care, expectations of treatment, the high costs of care, equity, marketing pressures, and therapeutic activism. Laser therapy in the dermatologic care of children is an exciting innovation that has transformed clinical practice and raised important social, ethical, and health policy issues. PMID- 8463893 TI - A prospective study of secondary prevention of child maltreatment. AB - This study sought (1) to retest an approach to the prediction of risk of child maltreatment and (2) to test the effect of a comprehensive prenatal and pediatric health services program on the rate of maltreatment. Of 2585 women screened at their first prenatal visit, 1154 qualified for the study. Risk assignment was determined by a structured interview. High-risk women (n = 314) were assigned to receive standard (high-risk control group; n = 154) or intervention (high-risk intervention group; n = 160) services throughout the prenatal period and during the first 2 years of their infants' life. A third group (low-risk control group; n = 295) was selected among low-risk women and received standard care without intervention services. State records were searched for substantive reports of child maltreatment up to 36 months after birth. Physical abuse was found for 5.1% of the study population; neglect was substantiated for 5.9%. Prediction efforts were effective in identifying risk of physical abuse but not of neglect. Comprehensive health services did not alter the reported abuse rate for high-risk parents and was associated with an increased number of neglect reports. Intervention reduced subject attrition and appeared to serve as a bias for detection of maltreatment. Thus this long-term, prospective approach was ineffective for child abuse prevention, perhaps because of detection biases and societal changes. PMID- 8463894 TI - Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine. AB - OBJECTIVE: The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States. The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b. DESIGN: This study was a prospective, bimonthly survey of pharyngeal colonization with H. influenzae type b in children attending day care from October 1987 through September 1989. Vaccination status was determined from the medical record. SUBJECTS: We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid). MEASUREMENTS AND RESULTS: Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H. influenzae type b. Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H. influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02). No effect on colonization was found with PRP vaccination. CONCLUSIONS: Conjugate vaccination decreases H. influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children. PMID- 8463895 TI - Quantitative leukoviremia and immune complex-dissociated antigenemia as predictors of infection status in children born to mothers infected with human immunodeficiency virus type 1. AB - Four methods of culturing human immunodeficiency virus type 1 (HIV-1) from peripheral blood mononuclear cells and two serum antigen tests were assessed as predictors of infection status in children born to HIV-1-infected mothers. Of 36 infants whose cocultures were quantitative, all 15 who were deemed to be infected with HIV-1 (nine with symptoms, six without symptoms) by clinical criteria or persistence of Western blot reactive antibody had positive culture results, and all 21 uninfected seroreverters had negative culture results (sensitivity = 100%; specificity = 100%). Quantitative coculture was more sensitive than a technique in which cells were counted and stimulated with phytohemagglutin but not cocultivated with cells from seronegative donors, and more sensitive than two other qualitative techniques evaluated in samples from 80 children, in which cells were not enumerated before culture. The level of leukoviremia in children with symptoms did not differ appreciably from the level of leukoviremia in symptom-free infected children. Among those with positive results on quantitative coculture, only 40% also had free HIV-1 antigen in serum, whereas 86% had antigen in immune complexes. Among the methods evaluated, quantitative HIV-1 coculture was the best indicator of infection status in children. PMID- 8463896 TI - Atypical (non-diarrhea-associated) hemolytic-uremic syndrome in childhood. AB - We describe the clinical and laboratory features of 20 children who were seen during the past 20 years with idiopathic nondiarrhea-associated hemolytic-uremic syndrome. There was no seasonal variation in time of onset; a genetic pre disposition seemed likely in two of the cases. The prodromal illness was nonspecific and by definition did not include diarrhea. Hypertension was a major problem in the majority of the patients. Five died, three during the initial illness; four are in end-stage renal failure, and all but two of the survivors have residual nephropathy. Eleven patients had a "relapsing" course; up to eight additional documented episodes of hemolytic-uremic syndrome occurred in individual patients. Of the nine children treated before 1980, three died shortly after onset, two never recovered function after the initial illness, one had a relapsing course and died later, and one had residual nephropathy. Plasma exchange was introduced for the management of non-diarrhea-associated hemolytic uremic syndrome in 1980; since then, all of the 11 patients have recovered function after the initial episode, but 10 of them had relapses. It appears that with the introduction of plasma exchange there has been an improved outcome in the initial phase, but the survivors tend to have relapses. Atypical (non diarrhea-associated) hemolytic-uremic syndrome is a heterogeneous yet distinct subgroup of hemolytic-uremic syndrome that differs from diarrhea-associated hemolytic-uremic syndrome on epidemiologic, clinical, laboratory, histologic, and prognostic grounds. PMID- 8463897 TI - Economic evaluation of intravenous immune globulin therapy for Kawasaki syndrome. AB - OBJECTIVE: To determine the costs and clinical outcomes of three alternative treatments of the acute phase of Kawasaki syndrome: aspirin alone; low doses of intravenously administered immune globulin (IVIG-LD), 400 mg/kg per dose for 4 days; and high doses of intravenously administered immune globulin (IVIG-HD), 2.0 gm/kg for one dose. DESIGN: A model was developed that assumed the inclusion of 100 patients with acute Kawasaki syndrome in each treatment option. Costs were valued by using the Chedoke-McMaster Corporate Cost Model in 1992 Canadian dollars. Clinical outcome, based on the published literature, was measured by the prevalence of coronary artery dilation at 7 weeks from the diagnosis of Kawasaki syndrome. RESULTS: For every 100 patients with Kawasaki syndrome, the cost was reduced by $323,400 when aspirin therapy alone was changed to IVIG-HD therapy and 14 cases of coronary artery dilation were thereby prevented. When IVIG-HD therapy was compared with IVIG-LD therapy, the cost was reduced by $118,200 because two cases of coronary artery aneurysm were prevented. This latter result was sensitive to the duration of hospitalization, with IVIG-HD costing $8500 more for every 100 patients than IVIG-LD when it was assumed that both groups were hospitalized for 5 days, an unlikely occurrence. CONCLUSIONS: Treatment with IVIG HD for Kawasaki syndrome is preferred because it results in both lower costs and lower rates of coronary artery dilation. PMID- 8463898 TI - Psychologic and psychoeducational consequences of thyroxine therapy for juvenile acquired hypothyroidism. AB - The observation of severe behavioral reactions or learning problems in three teenagers treated with L-thyroxine for juvenile acquired hypothyroidism prompted us to conduct a prospective study of achievement and behavioral characteristics of patients with newly diagnosed juvenile acquired hypothyroidism. On diagnosis of juvenile acquired hypothyroidism and before treatment with L-thyroxine, 23 children and adolescents underwent a comprehensive battery of psychoeducational tests, which was repeated after 3, 12, and 24 months of replacement therapy. Results revealed that adverse behavioral reactions and learning problems were relatively rare in these children, although symptoms of juvenile acquired hypothyroidism were associated with increased distractibility, hyperactivity, and poorer achievement. The least gain in achievement was made by children with more severe hypothyroidism at diagnosis; children with the best psychologic outcome were those who achieved euthyroidism more slowly. We conclude that severe behavioral manifestations of L-thyroxine therapy for juvenile acquired hypothyroidism are uncommon, but mild behavioral symptoms and poorer school achievement may occur in about 25% of patients, who represent the most severe cases at diagnosis. PMID- 8463899 TI - Relationship of genotype to early pulmonary function in infants with cystic fibrosis identified through neonatal screening. AB - To determine whether pulmonary function in infants with asymptomatic cystic fibrosis is related to genotype, we studied 18 infants with cystic fibrosis identified through neonatal screening and 18 healthy control infants. Infants with cystic fibrosis (mean age, 2.0 months; range, 1.0 to 4.6 months) were identified from June 1990 to September 1991 through a statewide screening program based on elevated immunoreactive trypsinogen concentrations. Pulmonary function testing was done before and after inhalation of albuterol. There were no differences in pulmonary function between the cystic fibrosis group and the control infants (mean age, 2.7 months; range, 0.9 to 4.5 months). However, infants homozygous for the delta F508 deletion (n = 10) differed from infants with other genotypic variants of cystic fibrosis and control infants with respect to respiratory system resistance (79.4 +/- 11.5 vs 52.0 +/- 3.8 vs 55.5 +/- 5.0 cm H2O/L per second, respectively; p = 0.04) and specific conductance (0.15 +/- 0.02 vs 0.21 +/- 0.02 vs 0.21 +/- 0.02 cm H2O-1 sec-1, respectively; p = 0.02). Infants homozygous for the delta F508 deletion, but not other infants, responded to albuterol with a decrease in respiratory system resistance. We conclude that infants with asymptomatic cystic fibrosis homozygous for the delta F508 deletion have early evidence of airways obstruction and may need early respiratory treatment. PMID- 8463900 TI - Resting metabolic rate in six- to ten-year-old obese and nonobese children. AB - The resting metabolic rate (RMR) and body composition of 130 obese and nonobese prepubertal children, aged 6 to 10 years, were assessed by indirect calorimetry and skin-fold thickness, respectively. The mean (+/- SD) RMR was 4619 +/- 449 kJ.day-1 (164 +/- 31 kJ.kg body weight-1 x day-1) in the 62 boys and 4449 +/- 520 kJ.day-1 (147 +/- 32 kJ.kg body weight-1 x day-1) in the 68 girls. Fat-free mass was the best single predictor of RMR (R2 = 0.64; p < 0.001). Step-down multiple regression analysis, with independent variables such as age, gender, weight, and height, allowed several RMR predictive equations to be developed. An equation for boys is as follows: RMR (kJ.day-1) = 1287 + 28.6 x Weight(kg) + 23.6 x Height(cm) - 69.1 x Age(yr) (R2 = 0.58; p < 0.001). An equation for girls is as follows: RMR (kJ.day-1 = 1552 + 35.8 x Weight (kg) + 15.6 x Height (cm) - 36.3 x Age (yr) (R2 = 0.69; p < 0.001). Comparison between the measured RMR and that predicted by currently used formulas showed that most of these equations tended to overestimate the RMR of both genders, especially in overweight children. PMID- 8463901 TI - Renin-angiotensin-aldosterone system in healthy subjects aged ten to eighteen years. AB - We obtained normative data for plasma renin activity (PRA) and plasma aldosterone concentration from a biracial sample of 195 healthy, normotensive children and adolescents aged 10 to 18 years. The sample included 119 boys and 76 girls, of whom 103 were black and 92 were white. The mean PRA value (+/- SD) was 2.52 +/- 1.95 ng/ml per hour, with minimal and maximal values of 0.1 and 13.50 ng/ml per hour. The mean plasma aldosterone concentration was 12.56 +/- 8.59 ng/ml, with minimal and maximal values of 1.6 and 50.1 ng/ml. We also examined the effects of subject characteristics and electrolyte intake. The slope relating sodium excretion to PRA was negative and highly significant (slope = -0.01; p < 0.003). The slope relating PRA to plasma aldosterone concentration was positive and highly significant (slope = 1.59; p < 0.0001). We did not observe differences in either variable as a function of age, sex, race, or family history of hypertension. These results suggest that differences based on race and family history of hypertension observed in adults are not present in youth. PMID- 8463902 TI - Prospective analysis and classification of patients with cystinuria identified in a newborn screening program. AB - Patients who inherit mutant cystinuria genes excrete high concentrations of cystine, ornithine, arginine, and lysine in the urine. At least three variants of cystinuria can be distinguished in heterozygotes. To determine whether certain combinations of mutant genes are more disadvantageous than others, we analyzed amino acid excretion in families of 17 probands with cystinuria identified by the Quebec neonatal screening program. Parents of the probands were classified into the three known phenotypes by calculating the sum of cystine, ornithine, arginine, and lysine excretion. Although parents of type I/I homozygotes excreted amounts of cystine in the normal range, their offspring excreted significantly greater amounts of urinary cystine than did children who have type I/III genetic compounds. This observation suggests that types I and III cystinuria mutations might involve two distinct genetic loci. Children with type I/I homozygous cystinuria often excrete cystine at levels greater than the theoretic solubility limit and may be at greatest risk for nephrolithiasis. We outline an approach to monitoring children with cystinuria who come to medical attention before formation of cystine stones. PMID- 8463903 TI - Peroxisomal disorders in children: immunohistochemistry and neuropathology. AB - Immunohistochemical studies with antisera against four peroxisomal enzymes, catalase and beta-oxidation enzymes (acyl-coenzyme A oxidase, bifunctional protein, and 3-ketoacyl-CoA thiolase), were performed on brain, liver, and kidney specimens from patients with peroxisomal disorders, as well as specimens from three control subjects, by using conventional paraffin-embedded autopsy material. The patients included eight with Zellweger syndrome and one with neonatal adrenoleukodystrophy. In the liver and kidney specimens from all patients, except one with Zellweger syndrome, diffuse immunostaining with all antisera in the cytoplasm of hepatocytes and renal tubular epithelium suggested an absence of peroxisomes but the presence of peroxisomal enzymes. Examination of brain specimens indicated a weak or negative reaction of neurons in the cerebral cortex and a weak reaction of glial cells in the white matter, which suggested maturational delay compared with control subjects. The delayed immunoreactive pattern of peroxisomal enzymes in Zellweger syndrome and neonatal adrenoleukodystrophy may be related to the significant neuropathologic features of polymicrogyria and dysmyelinogenesis. One patient with Zellweger syndrome had a unique finding of a positive granular catalase reaction and a negative reaction with antisera to 3-ketoacyl-coenzyme A thiolase, which suggested a diagnosis of pseudo-Zellweger syndrome. This study validates the application of these immunohistochemical methods to the study of peroxisomal enzymes. Use of these methods improves the accuracy of diagnosis of peroxisomal disorders. PMID- 8463904 TI - Effect of treatment with glycine and L-carnitine in medium-chain acyl-coenzyme A dehydrogenase deficiency. AB - To assess the relative contribution of glycine and carnitine conjugation pathways to total acyl-group excretion, we investigated the excretion of C6 to C10 dicarboxylic acids, C6 to C8 acylglycines, and C6 to C8 acylcarnitines in five symptom-free patients with medium-chain acyl-coenzyme A dehydrogenase deficiency during sequential 1-week periods as follows: (1) no treatment, (2) oral supplementation with glycine, 250 mg/kg per day, (3) oral supplementation with L carnitine, 100 mg/kg per day, and (4) oral supplementation with both combined. In untreated patients, acylglycines and acylcarnitines represented 60% and less than 1% of the total metabolite excretion, respectively; the average acylglycine/acylcarnitine ratio was 70:1. Oral supplementation with glycine did not alter the excretion of acylglycines or acylcarnitines. L-Carnitine supplementation increased the acylcarnitine excretion sixfold and caused a 60% reduction in acylglycine excretion (p < 0.001); however, even with carnitine supplementation, acylglycine excretion was still 10 times greater than that of acylcarnitines. The results suggest that glycine conjugation was the major pathway for the disposal of C6 to C8 acyl moieties and that oral L-carnitine supplements may inhibit glycine conjugation. The findings cast doubt on the value of long-term treatment of medium-chain acyl-coenzyme A dehydrogenase deficiency with L-carnitine. PMID- 8463905 TI - Verification bias in pediatric studies evaluating diagnostic tests. AB - Improperly designed evaluations of diagnostic tests may lead to inaccurate conclusions about a test's accuracy. One problem, verification bias, occurs if subjects are not equally likely to have the diagnosis verified by a gold-standard evaluation and if selection for further evaluation is dependent on the diagnostic test result. To determine whether verification bias is a problem in pediatric studies of diagnostic tests, we conducted a critical appraisal of all studies evaluating diagnostic tests published in three pediatric journals during a 3-year period. Thirty-six percent were subject to verification bias. The most prevalent cause was restriction of the patient sample to those whose diagnosis had been verified by a gold standard evaluation, when the decision to obtain the gold standard was influenced by the diagnostic test result. Verification bias may have serious effects on the estimated sensitivity and specificity of a test. Improved awareness of the potential for verification bias may help physicians improve their selection and interpretation of diagnostic tests and thereby improve the quality and efficiency of patient care. PMID- 8463906 TI - Long-term outcome of Lyme disease in children given early treatment. AB - Sixty-three patients treated with appropriate antimicrobial therapy between 1985 and 1990 for physician-documented erythema migrans were identified. A telephone interview program 1 to 6 years after the initial episode of Lyme disease revealed that none of the patients had evidence of carditis, arthritis, or neurologic complications attributable to Lyme disease. A new episode of erythema migrans was reported in 7 (11%) of the patients 1 to 4 years after the initial episode. PMID- 8463907 TI - Acute splenic sequestration together with aplastic crisis caused by human parvovirus B19 in patients with sickle cell disease. AB - Three children with homozygous sickle cell disease, 22 months and 8 and 10 years of age, had clinical and hematologic manifestations of aplastic and splenic sequestration crisis simultaneously. They had an acute drop in hemoglobin level (16, 20, and 45 gm/L), reticulocytopenia (0.1%, 0.6%, and 0.3%), and sudden splenic enlargement. Evidence of recent parvovirus infection was demonstrated. PMID- 8463908 TI - Differentiation of systemic juvenile rheumatoid arthritis from acute leukemia near the onset of disease. AB - Many children with acute leukemia have musculoskeletal complaints and non specific hematologic abnormalities. A total of 10 children with acute leukemia and 10 with systemic juvenile rheumatoid arthritis were compared to delineate which early features could differentiate these diagnoses. Attention to evolving hematologic abnormalities and musculoskeletal findings may expedite diagnosis of these diseases. PMID- 8463909 TI - Recurrence of insulin-dependent diabetes mellitus after transient neonatal diabetes: a report of two cases. AB - Insulin-dependent diabetes mellitus developed in two patients with transient neonatal diabetes after more than 5 years without insulin therapy. The absence of islet cell antibodies and of the typical HLA types suggests that they may have a nonimmunologic form of diabetes. PMID- 8463910 TI - Epidermolysis bullosa and severe ulcerative colitis in an infant. AB - An infant with epidermolysis bullosa simplex had diarrhea at 3 weeks of age; severe ulcerative colitis was subsequently diagnosed. Epidermolysis bullosa simplex has not been associated with gastrointestinal disease except for buccal ulceration. PMID- 8463911 TI - Diaphragmatic hernia in tetrasomy 12p mosaicism. AB - Twelve infants with diaphragmatic hernias plus other anomalies who had mosaicism for tetrasomy isochromosome 12p (Pallister-Killian syndrome) are reviewed. A newborn infant with a diaphragmatic hernia plus dysmorphic features and a normal peripheral blood karyotype should have chromosome analysis performed on fibroblasts or bone marrow. PMID- 8463912 TI - Bilateral fiberoptic bronchoalveolar lavage in acute unilateral lobar pneumonia. AB - Bilateral cultures of bronchoalveolar lavage fluid were obtained from eight children with unilateral lobar pneumonia. In four patients bacterial pathogens were not isolated from lavage of the radiologically normal side but were subsequently cultured from the consolidated segment. This pattern helped to exclude contamination by oropharyngeal flora of bronchoalveolar lavage fluid. Bilateral bronchoalveolar lavage may help in the interpretation of lower respiratory tract cultures obtained by fiberoptic bronchoscopy. PMID- 8463913 TI - Randomized study of high-frequency oscillatory ventilation in infants with severe respiratory distress syndrome. HiFO Study Group. AB - We conducted a multicenter, prospective, noncrossover, randomized study to determine whether high-frequency oscillatory ventilation (HFOV) would decrease the development or progression of air leak syndrome in infants with severe respiratory distress syndrome. Air leak syndrome was defined as pulmonary interstitial emphysema or gross air leak such as pneumothorax. Infants were eligible for study entry if they were less than 48 hours of age and had severe respiratory distress syndrome, defined by peak inspiratory pressure or the presence of air leak syndrome. Infants who weighed > or = 0.5 kg at birth were randomly assigned to receive either conventional ventilation (CV) or HFOV. HFOV was provided by a ventilator that operated at 15 Hz, with a 1:2 inspiratory/expiratory ratio and no background tidal breaths. Severity of pulmonary interstitial emphysema was scored independently by two neonatologists unaware of the infants' ventilatory group. Gross air leak severity was scored according to the number of chest tubes required and duration of air leak. Eighty six infants received HFOV; 90 received CV. During the first 24 hours of the study, patients in the HFOV group received significantly higher mean airway pressure and lower inspired oxygen concentration, had significantly lower arterial carbon dioxide tension, and had a higher ratio of arterial to alveolar oxygen tension. When the HFOV and CV groups were compared with control for birth weight strata, study site, and inborn versus outborn status, HFOV significantly reduced the development of air leak syndrome in those patients who entered the study without the syndrome. We conclude that HFOV, when the strategy employed in this study is used, provides effective ventilation, improves oxygenation, and significantly reduces the development of air leak syndrome in infants with severe respiratory distress syndrome. PMID- 8463914 TI - Time of first stool in extremely low birth weight (< or = 1000 grams) infants. AB - The time of first stool was studied in 144 infants with a birth weight of 1000 gm or less. Median age at passage of the first stool was 3 days, and 90% of the infants passed stool by 12 days after birth. There was no relationship between the time of passage of the first stool and either birth weight or gestational age. Of the 114 infants, 88 (77%) passed stool before the initiation of any enteral feeding. The passage of the first stool was delayed in male compared with female infants (p = 0.03). PMID- 8463915 TI - Lactic acid as a predictor for erythrocyte transfusion in healthy preterm infants with anemia of prematurity. AB - Elevated blood lactate levels that declined to normal after erythrocyte transfusion were observed in 17 of 37 otherwise healthy infants with anemia of prematurity (26.1 +/- 2.1 mg/dl vs 12.3 +/- 0.9 mg/dl; p < 0.001). Posttransfusion heart rate in this group decreased from 155 +/- 1 beats/min to 150 +/- 2 beats/min (p = 0.01). Blood lactate concentration may be a predictor of the need for transfusion in anemia of prematurity. PMID- 8463916 TI - Effect of low intravaginal doses of prostaglandin E2 on the closure time of the ductus arteriosus in term newborn infants. AB - Seventeen term newborn infants (control subjects) and 17 whose mothers had been given intravaginal doses of prostaglandin E2 (PGE2) were examined serially by color Doppler echocardiography to determine whether maternal PGE2 prolonged ductal patency. No clinically relevant differences in closure times were found. Low-dose intravaginal PGE2 therapy was not associated with prolonged ductal patency in term infants. PMID- 8463917 TI - Nephrocalcinosis in very low birth weight neonates: family history of kidney stones and ethnicity as independent risk factors. AB - Serial renal ultrasonography was performed in 50 consecutive neonates with birth weights less than 1200 gm who survived to at least 3 weeks of age. Nephrocalcinosis developed in 8 (67%) of 12 white and only 6 (16%) of 38 nonwhite infants (p < 0.01). Seven (78%) of nine infants with a family history of kidney stones had nephrocalcinosis compared with only 7 (17%) of 41 without a family history of kidney stones (p < 0.001). We conclude that nephrocalcinosis in our population of very low birth weight neonates is significantly and independently associated with a family history of kidney stones and white race. PMID- 8463918 TI - Neonatal sepsis caused by a new group B streptococcal serotype. AB - Two infants with typical clinical presentations for invasive neonatal group B streptococcal disease caused by a new serotype, type V, are described. Organisms of this capsular type should be sought among isolates from sick neonates to evaluate their prevalence and associated patterns of disease. PMID- 8463919 TI - Identification of nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children with juvenile rheumatoid arthritis. AB - In a cohort of children with juvenile rheumatoid arthritis treated with nonsteroidal antiinflammatory drugs and referred for gastrointestinal complaints, more than 75% had gastritis, antral erosions, or ulcers. Epigastric pain strongly correlated with documented gastroduodenal injury. Therapy with ranitidine or misoprostol led to clinical improvement. Nonsteroidal antiinflammatory drugs are associated with significant gastrointestinal abnormalities in children. PMID- 8463920 TI - Efficacy of herbal tea preparation in infantile colic. AB - We evaluated the effect of an herbal tea preparation on infantile colic in a prospective double-blind study. The use of tea eliminated the colic in 19 (57%) of 33 infants, whereas placebo was helpful in only 9 (26%) of 35 (p < 0.01). The mean colic score was significantly improved in tea-treated infants. No significant differences were noted between groups regarding number of night wakings. PMID- 8463921 TI - Prospective study of the electrocardiographic effects of imipramine in children. AB - Because imipramine and desipramine have been implicated in sudden death in children, noninvasive electrophysiologic data were accumulated in 25 patients. Two children were excluded on the basis of resting electrocardiographic and Holter abnormalities. The remaining 23 patients received imipramine to a maximum dose of 5 mg/kg or a serum level of 150 to 250 ng/ml. Consistent but clinically insignificant resting electrocardiographic changes occurred during treatment. Ambulatory electrocardiographic monitoring may be useful when one is assessing the cardiovascular risks of imipramine therapy. PMID- 8463922 TI - Single-dose pharmacokinetics of recombinant human erythropoietin in preterm infants after intravenous and subcutaneous administration. AB - Pharmacokinetics of recombinant human erythropoietin (rHuEPO) were studied in a group of very low birth weight infants after both intravenous and subcutaneous administration. The volume of distribution was larger and the clearance more rapid than those reported in adults. The maximum concentration of erythropoietin after subcutaneous doses of rHuEPO was variable, but bioavailability was high (42%) compared with values reported in adults. These observations could be useful in optimizing treatment of the anemia of prematurity with rHuEPO. PMID- 8463923 TI - Heparin-induced thrombocytopenia. PMID- 8463924 TI - Defining outcomes for otitis media studies. PMID- 8463925 TI - Aortic dissection and rupture in Turner syndrome. PMID- 8463926 TI - Treatment of Turner syndrome with growth hormone. PMID- 8463927 TI - Management of chlamydial infections in adolescents. PMID- 8463928 TI - Mothers' supervision and perception of young children's risk of unintentional injury in the home. AB - Investigated whether control exerted through supervision is believed by mothers to reduce risk of unintentional injury to their children. 150 mothers of 1-, 2-, and 3-year-old children rated the risk of their child having an injury and indicated what injuries they anticipated in different rooms of the home under four conditions of supervision. A clear effect of supervision was observed in that rated risk and the number of anticipated injuries decreased depending on whether the mother was in the same room or not. Furthermore, a decrease was found when the mother was in the same room engaged in the same activity as the child (either playing with or being assisted by the child). The observed effects of supervision were less strong for older children and for rooms perceived as less dangerous. PMID- 8463929 TI - Empirical selection of psychosocial treatment targets for children and adolescents with diabetes. AB - Used an empirical approach to determine psychosocial variables related to optimal metabolic control of diabetes in two samples (total n = 56) of children and their families. Children and adolescents classified as either in optimal or nonoptimal control of diabetes (based on glycosylated hemoglobin results) completed self report measures on variables of anxiety, coping, family environment and health locus of control, and a structured interview. Parents completed parallel self report measures and a child behavior checklist. Children in optimal control of diabetes had more structured and controlling family environments, and more frequently believed that "powerful others" were responsible for their health. There was a marginally significant difference in knowledge, with children in poorer metabolic control showing better knowledge about diabetes and its management than children in optimal control. The study illustrates an empirical approach to the selection of psychosocial treatment targets for children with diabetes, and underscores the importance of parental involvement with the diabetes regimen to ensure optimal control of diabetes in both children and adolescents. PMID- 8463930 TI - Safety hazards in households with young children. AB - Interviewed 230 mothers of young children concerning in-home observations of safety hazards related to burns, poisoning, and falls, and self-reported measures of maternal supervision, locus of control, social support, and safety attitudes. These were supplemented by measures of mothers' risk perceptions, stress and coping, their child's previous injury experience, and indicators of the family's socioeconomic status (SES) collected by telephone survey. SES was an important predictor of observed home hazards. Child-related variables, risk perceptions, and domain-specific attitudes had little influence on home hazards. Maternal supervisory style, rated on dimensions of protectiveness, was an important correlate of all types of household hazards. Results suggest that residential injury prevention strategies for young children should stress active as well as passive countermeasures. PMID- 8463931 TI - Measures of children's injuries: self-reported versus maternal-reported events with temporally proximal versus delayed reporting. AB - Although attention has recently been focused on understanding and preventing children's injuries, much controversy exists over the best data collection methods for examining child injuries. This study examined three methodological issues relevant to childhood injury data collection including the length of time children and parents can be expected to meaningfully recall injuries, whether the parent or child is a preferred informant about the injury, and the potential use of near injuries as a proxy measure for actual child injuries. Both children and their mothers were individually interviewed every 2 weeks for a total of 6 months about both injuries and near injuries. In addition, at the end of the 6-month period, they were asked to recall all injuries that occurred during those 6 months. Overall, children reported more injuries than mothers. Children recalled far fewer and mothers recalled slightly fewer events than had been reported in the biweekly interviews. There were fewer near injury than actual injury events reported, although this varied across categories, with some categories (e.g., car passenger injuries) having more near than actual injuries, and other categories (e.g., cuts, bumps, and bruises) having many more actual than near injuries reported. Limitations of the project are discussed and implications for future research advanced. PMID- 8463932 TI - Stress management training for adolescents with diabetes. AB - Evaluated the effects of stress management training (SMT) for adolescents with diabetes in a 9-month controlled treatment-outcome study. Nine patients were randomly assigned to a stress management group while another 10 patients served as controls and received standard outpatient treatment. The treatment program consisted of 10 sessions over 3 months, 3 additional sessions over 3 months, and a 3-month follow-up without treatment. Diabetes-specific stress decreased significantly for patients in the SMT group over the course of the intervention and follow-up. However, metabolic control, regimen adherence, coping styles, and self-efficacy about diabetes were unchanged. These findings suggest a SMT program for adolescents with diabetes may be helpful in reducing diabetes-specific stress, but additional procedures are necessary to improve adherence, coping styles, and metabolic control. PMID- 8463933 TI - Treatment adherence difficulties among children with cancer: the role of parenting style. AB - Investigated the prevalence of treatment adherence problems among children undergoing cancer treatment and explored the relationship of sociodemographic factors, child functional status, and parenting style to these difficulties. Nurse ratings of adherence difficulties encountered during the cancer treatment regimen were completed on 77 children and their caregivers. A subset of caregivers also completed a measure of parenting attitudes and practices. Results indicated that certain adherence difficulties were related to the child's age and functional status, the family's socioeconomic status (SES), and parenting style. The child's age was related to adherence to procedure-related tasks; younger children had more frequent problems with completing these tasks. More functional children had a greater number of adherence problems. Families with a lower SES had more difficulties with timeliness and cancellations/delays of clinic appointments and promptness of reporting of the child's reactions to treatment. Children of caregivers who had a more "supportive" parenting style (were more sensitive to children's input, had a less restrictive attitude towards parenting, and were more nurturant) canceled and delayed fewer appointments, were on time more frequently for appointments, and reported reactions to treatment with less delay. Implications of these findings for future research on treatment adherence and for clinical interventions are discussed. PMID- 8463934 TI - Effective and ineffective management behaviors of parents of infants and young children with asthma. AB - To define the specific objectives of a planned behavioral intervention directed toward parents of very young children with asthma, 574 detailed descriptions of ineffective and effective asthma management behaviors of parents of infants and young children (through 6 years of age) with asthma were collected via interviews with 117 physicians and other health professionals and 112 parents. Analysis of these data resulted in the identification of 130 ineffective and effective asthma management behaviors of parents that could be grouped in five major areas of responsibility: symptom intervention; symptom prevention; use of medical and educational resources; communication among caregivers; and child development and family relationships. This report presents the methodology of the study, describes the identified behaviors, and discusses implications of the results for the development of a behavioral intervention to improve asthma management by parents. PMID- 8463935 TI - Conceptions of illness by children with juvenile rheumatoid arthritis: a cognitive developmental approach. AB - Investigated the conceptions of illness and accuracy of understanding about their disease for children with juvenile rheumatoid arthritis (JRA). 54 children between the ages of 6 and 17 were interviewed individually about various aspects of JRA, with results suggesting that accuracy and illness conceptions could be reliably measured. As predicted, children's understanding about their disease followed a developmental progression, with older children demonstrating a more sophisticated understanding of JRA than younger children (significant differences between age groups on 3 of the 5 questions). Multiple regression analysis indicated that conceptual level (p < .001) was a better predictor of the child's accuracy of knowledge than was age (ns). Despite the developmental progression, there were a significant number of children functioning below the level expected for their age. In fact, the majority (75%) of children exhibited an understanding of JRA at the concrete operational level of cognitive development. The within subject variability and striking misconceptions argue for ongoing evaluation of each child's understanding as a way to improve educational efforts. PMID- 8463936 TI - Microbial composition and pattern of antibiotic resistance in subgingival microbial samples from patients with refractory periodontitis. AB - A series of 993 subgingival microbial samples sent to a diagnostic microbiology laboratory included 196 samples that could be identified as compatible with a clinical diagnosis of refractory or recurrent periodontitis. In descending order of prevalence the associated microbiota included Bacteroides forsythus (84%), spirochetes (83%), motile rods (76%), Fusobacterium species (68%), Porphyromonas gingivalis (63%), Campylobacter rectus (47%), Capnocytophaga species (38%), Prevotella intermedia (23%), Peptostreptococcus micros (18%), Actinobacillus actinomycetemcomitans (16%), Candida (14%), enteric rods (9%), Staphylococcus species, not including aureus (5.6%). Eikenella corrodens (3%), Staphylococcus aureus (1.5%), and Enterococcus species (< 1%). Antibiotic resistance to tetracycline, penicillin G, or metronidazole was particularly noticeable for enteric rods, Fusobacterium species, Capnocytophaga species, Staphylococcus, and Actinobacillus actinomycetemcomitans. It was largely absent for Campylobacter rectus. No antibiotic sensitivity data were obtained for Porphyromonas gingivalis or Bacteroides forsythus, as these species were detected by immunofluorescence. The results indicate that a substantial number of microorganisms associated with refractory periodontitis are variably resistant to commonly-used antibiotics. Diagnostic microbiology must be considered an essential adjunct to the therapist faced with periodontal lesions refractory to conventional treatment. PMID- 8463937 TI - Colonization of retrieved polytetrafluoroethylene membranes: morphological and microbiological observations. AB - Polytetrafluoroethylene membranes (ePTFE) used in guided tissue regeneration (GTR) are accessible to colonization by oral bacteria. The bacterial composition of the adherent biomass is unknown. We examined a total of 6 membranes that were retrieved after 4 to 6 weeks from human periodontitis sites, using optical and transmission electron microscopy (TEM) as well anaerobic cultivation. Five of the 6 membranes provided the microbiological data and microscopic data. TEM revealed an organized microbial mass covering the surfaces and also within the interstices of the open microstructure and occlusive portions of the membranes. Numerous bacterial forms including cocci, rods, and filaments with an interbacterial matrix, frequently in microcolonies, were identified. Anaerobic cultivation yielded Streptococcus and Actinomyces species with a minor component of Gram negative facultative rods comprised mainly of Haemophilus species. Candida species was recovered from one membrane. These data show that ePTFE is heavily colonized by oral bacteria during retention. The impact of bacterial colonization of ePTFE is not known but it seems reasonable to assume that colonization of membranes may affect connective tissue regeneration. Further studies will be needed to examine the effect of systemic antimicrobials on ePTFE colonization and in turn to examine the effect on GTR. PMID- 8463938 TI - Phenytoin increases gene expression for platelet-derived growth factor B chain in macrophages and monocytes. AB - The mechanism by which phenytoin (PHT) induces gingival overgrowth remains unclear. We hypothesized that PHT increases macrophage production of platelet derived growth factor (PDGF), an important cytokine in connective tissue growth and repair, and that excessive production PDGF in gingiva could lead to redundant growth. To test the hypothesis, rat peritoneal macrophages and human blood monocytes were cultured in the presence of PHT (5 to 20 micrograms/ml medium) or an equal volume of its solvent for 3 days and tested for expression of PDGF-B mRNA by in situ hybridization. Approximately 300 cells/culture well were examined (3 wells/drug level) for positive indication of PDGF-B mRNA. Data were compared by chi square test. All levels of PHT in both cell types induced a 2- to 8-fold increase in PDGF-B mRNA positive cells, significant in all cases at P < 0.001. Northern blot analysis of RNA from similarly cultured rat macrophages confirmed these findings. Cells treated with 10 micrograms PHT/ml medium or solvent revealed 2.2 +/- 0.3 and 1.0 +/- 0.2 (mean +/- SEM) arbitrary units PDGF mRNA respectively (t tests, P < 0.05). Additionally, rat macrophages were cultured in presence of 5 micrograms PHT/medium or its solvent and medium was analyzed for PDGF secretion by radioimmunoassay. Mean values (+/- SEM) were 1.28 +/- 0.49 and 0.78 +/- 0.07 ng/mg protein respectively (t test, P < 0.05). These data showed that PHT augmented the expression of c-sis, the gene for PDGF-B, and offered a possible explanation for PHT-induced gingival overgrowth. PMID- 8463939 TI - The plaque removal effects of single rinsings and brushings. AB - Chemical plaque removal is one mechanism whereby an agent could improve oral hygiene and gingival health. As with toothpastes most agents, when delivered as rinses, would be considered adjunctive to mechanical tooth cleaning procedures. The aim of this study was to determine whether selected commercial rinses exhibited clinically significant plaque removal properties alone or when combined with toothbrushing with water or a toothpaste. A group of 12 volunteers took part in this single blind, randomized placebo-controlled, 12 cell cross-over study, employing 6 rinses. During each regimen subjects accumulated plaque from a zero baseline over 72 hours. Plaque removal was then measured by index and area after first a single rinse of product and second a subsequent brushing with water or toothpaste. Prebrushing rinsing removed less than 5% of the plaque with little difference between agents. No rinse was more adjunctive than water to postrinse brushings. Most statistically significant differences arose with the chlorhexidine rinse being apparently less effective. However, the possibility of a disclosing dye interaction cannot be discounted as explaining this anomalous result. This study could not support any claim of a direct prebrushing rinse benefit greater than that provided by water to mechanical plaque removal by any of the products tested. PMID- 8463940 TI - Glycosaminoglycans and periodontal disease: analysis of GCF by safranin O. AB - The purpose of this study was to quantify glycosaminoglycans (GAG) released into the gingival crevicular fluid (GCF) during health, gingivitis, and adult periodontitis. The investigation tested the hypothesis that increased amounts of GAG can be measured in GCF associated with gingivitis and adult periodontitis as compared to health. An individual patient's sampling sites were assigned to either a health (control) group or 1 of 3 experimental groups, gingivitis, periodontal "maintenance" (perio-M), or periodontal "non-maintenance" (perio-NM) according to standard clinical criteria of pocket probing depth, bleeding on probing, and radiographic evidence of bone loss. The perio-M group was defined as a periodontal patient who had received a dental prophylaxis and/or root planning within 6 months prior to GCF collection. The perio-NM group had received no periodontal therapy during the previous 6 months. Subsequent to air-drying and isolation, GCF was collected by a microcapillary pipette held at the gingival margin. All fluid samples were digested overnight at 37 degrees C with 25 micrograms of papain and analyzed for GAG content using a chondroitin-4-sulfate standard. Data generated from safranin "O" dye binding assays of GAG revealed 4.41 +/- 9.82 ng GAG from the health (control) group (n = 23); the gingivitis group (n = 13) showed 15.23 +/- 11.85 ng GAG/sample; perio-M group (n = 11) showed 23.64 +/- 12.98 ng GAG/sample and the perio-NM group (n = 12) exhibited 119.08 +/- 33.14 ng GAG/sample.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8463941 TI - Fructosamine as a possible monitoring parameter in non-insulin dependent diabetes mellitus patients with periodontal disease. AB - Fructosamine assay is a new test used in the diagnosis and monitoring of diabetic patients. This assay may be of interest to the periodontist for, while the traditional plasma glucose value would give a general view and information about diabetic control at a certain point, the fructosamine concentration gives an indication of the plasma glucose level over a considerable period of time, such as 1 to 3 weeks. We investigated whether there was any relation between the diseased state of the periodontal tissues and plasma fructosamine and the plasma glucose values in non-insulin dependent diabetes mellitus (NIDDM) patients. We found that fructosamine correlated with the degree of gingival bleeding, however serum glucose levels had little or no correlation. PMID- 8463942 TI - Serum IgG and IgM levels to bacterial antigens in necrotizing ulcerative gingivitis. AB - Previous studies of the systemic antibody response in necrotizing ulcerative gingivitis (NUG) have elicited varying results. The purpose of this study was to determine the humoral response to site-specific isolates of microbiota associated with NUG. Sera from 21 active NUG subjects and 21 age-sex-race matched controls were assessed for IgG and IgM antibodies to 4 clinical isolates of Prevotella intermedia and 3 clinical isolates of Treponema species. P. intermedia and Treponema strains were isolated from active and inactive sites of NUG patients and gingivitis sites of controls. P. intermedia was also isolated from noninflamed sites of the controls. IgG and IgM serum levels to these 7 bacteria were measured by ELISA. Compared to control subjects, the NUG sera exhibited significantly lower IgG and IgM levels to all 4 isolates of P. intermedia (P < or = 0.001). It was also noted that sera from NUG subjects had elevated IgM levels to all 3 spirochete isolates but significantly higher only to the spirochete isolated from a gingivitis site of a control subject (P < or = 0.005). The data suggest that failure to mount a substantial antibody response to P. intermedia may be associated with onset of disease activity in NUG. However, the assumed lack of "biological significance" between differences in antibody responses measured indicates the relationship is weak or nonexistent. It also appears that antibody response to spirochetes is not associated with onset of NUG. PMID- 8463943 TI - Histologic evaluation of periodontal attachment apparatus following the insertion of a biodegradable copolymer barrier in humans. AB - The purpose of this study was to histologically evaluate the effectiveness of polylactide:polyglycolide 50:50 (DL-PLGA) as a barrier to prevent epithelial migration and to promote new connective tissue attachment. Mucoperiosteal flaps were performed on 17 human teeth. DL-PLGA membrane was placed over the roots and alveolar bone. DL-PLGA was not placed over control teeth. Ninety days following surgery, block sections were obtained and processed for histologic evaluation. All specimens revealed a mean length of epithelial attachment within physiologic limits and recession of the gingival margin. There was little or no reattachment of the connective tissue. It is concluded that this copolymer barrier did not prevent epithelial migration nor enhance connective tissue attachment to human roots with severe horizontal bone loss and active periodontal disease. PMID- 8463944 TI - Experimental gingivitis during pregnancy and post-partum: immunohistochemical aspects. AB - The histoimmunological response of 8 individuals was studied longitudinally in relation to the development of experimental gingivitis during pregnancy and post partum. At day 0 as well as at day 14 of experimental gingivitis the mean periodontal pocket bleeding index (PPBI) was higher during pregnancy than post partum, whereas the amount of plaque that accumulated was similar. The number of CD1 positive cells (mainly Langerhans) in the oral epithelium was found to be higher during pregnancy. In the sulcular epithelium, however, the number of these cells tended to decrease during pregnancy as compared to post-partum. The number of CD4 positive cells in oral and sulcular epithelium was increased during pregnancy (P < 0.05). It was speculated that this increase in the number of CD4 positive cells is confined to the Th-1 subset, since the number of CD14 positive cells (mainly macrophages and granulocytes) together with the number of B cells was found to be decreased during pregnancy. Th-1 cells are known to be cytotoxic against these HLA class II antigen bearing cells. Consequently, cytotoxicity directed against B cells and macrophages may result in diminished immunoresponsiveness in pregnancy gingivitis. PMID- 8463945 TI - Clinical furcation diagnoses and interradicular bone defects. AB - The purpose of the present study was to assess associations between clinical depth of involved furcations and their bony defect depth. Twelve patients with moderate to advanced periodontitis in molars were recruited for clinical evaluation of furcation involvement by 6 dentists. Two groups of 3 dentists were assigned to the right or left half of the dentition. All dentists assessed the clinical depth of involvement of the furcations using the Ramfjord index (2 mm) in patients 1 through 6, and using the Hamp index (3 mm) in patients 7 through 12. Diagnoses were made with calibrated and uncalibrated Nabers 2 probes. After the clinical assessments the patients received full mouth scaling and root planing. After reevaluation the molars were surgically exposed. During surgery the depth of the bony furcation defects was assessed using horizontal probing and impressions. Clinically assessed depth of furcation involvement was then compared with the surgical measurements. A total of 1,180 clinical furcation diagnoses were available, of which 426 could be surgically evaluated using both the straight probe and the impressions. These evaluations were done in a total of 72 furcations using probe and impressions. For the Ramfjord index, 5% of the clinical degree 1, 40% of the degree 2, and 43% of the degree 3 readings were overestimations. For the Hamp index, 7% of degree 1, 24% of degree 2, and 0% of degree 3 readings were overestimations. These clinical diagnoses were overestimations. Forty-three percent of surgical degree 3 involvements were not recognized when using the Ramfjord index, and 27% when using the Hamp Index. These results suggest that furcation diagnosis is of limited validity. PMID- 8463946 TI - Efficacy of 5 machining instruments in scaling of molar furcations. AB - The scaling efficacy of machining instruments was studied in the furcations of 100 extracted molars. The molars were divided into 5 groups with similar furcation anatomy, painted with artificial calculus, partly submerged in stone blocks, and the furcation entrances covered with a heavy rubber dam material. Ten mandibular and 10 maxillary molars were scaled by an experienced operator with each of the following instruments/inserts: ultrasonic instrument with either a prototype ball point insert or with a new pointed insert; ultrasonic instrument with a ball point insert; reciprocating hand-piece with new inserts for furcations; and a sonic scaler with a universal insert. The molar groups were coded and graded in a stereomicroscope by 2 independent examiners, and the rankings were tested with the Kruskal-Wallis test and the multiple comparisons between treatments test. The results revealed statistically significant differences between the instruments, as well as between different topographical areas of the furcations. The sonic scaler with a universal insert and the ultrasonic instrument with ball point inserts were significantly more efficient (P < 0.05) than the reciprocating handpiece with inserts in most of the areas studied. For mandibular molars, significantly better results (P < 0.05) were obtained for lingual furcation entrances than for furcation roofs. For maxillary molars, significantly better results (P < 0.05) were obtained for distal and buccal entrance areas than for furcation roofs and inside of mesial roots. The present study may give some guidance to the practitioner in choosing machining instruments for furcation cleaning as well as identifying the most difficult topographical areas to instrument. PMID- 8463947 TI - Effects of dilantin on monocytic growth factors. PMID- 8463948 TI - Re: Temperature differences at periodontal sites in health and disease. PMID- 8463949 TI - Re: Tooth morphology following root resection procedures in maxillary first molars. PMID- 8463950 TI - Motivational similarity and interpersonal evaluations: the role of ambiguity, self-derogation, and emotion. AB - The present study tests two hypotheses which are based on a motivational threat model of interpersonal evaluation: (a) Dominance- and dependency-oriented perceivers evaluate motivationally similar others less favorably only when evaluation pertains to an ambiguous attribute and perceivers score high on self derogation; and (b) the relatively unfavorable evaluation of the similar target person is mediated by an arousal process. Males observed a working dyad in which one man was dominant and the other dependent, but both were ambiguous on sociability. Throughout the observation, subjects' emotion-related skin conductance responses were monitored. Subjects then evaluated the target person they expected to meet and recalled information. Results supported the first hypothesis, but were only partially consistent with the second hypothesis. In addition, dominance-oriented perceivers produced more assertiveness constructs than dependency-oriented perceivers in free recall. The findings suggest that the threat model should be revised to include the moderating factors of attribute ambiguity and attitude toward the self, and perhaps also an additional mediating process: generalization of attitude toward the self to motivationally similar others. PMID- 8463951 TI - Self-awareness, task failure, and disinhibition: how attentional focus affects eating. AB - Dieting and nondieting subjects were given either failure or neutral performance feedback on a problem-solving task. Failure subjects were then assigned to one of three self-awareness conditions: One group was forced to watch a video clip of themselves failing on the problem-solving task, one group was asked to watch a distracting video clip on bighorn sheep, and the final group was asked to sit quietly for 10 minutes. Subjects were then allowed to eat as much ice cream as they wanted. Only in those conditions which allowed--or promoted--low self awareness (the failure/distraction and simple failure condition) did dieters show disinhibited eating. In the failure/videotape condition, which enforced high levels of self-awareness, eating in dieters remained inhibited. This supports the proposal that a reduction in self-awareness is necessary for lifting of inhibitions. Eating in nondieters was reduced in the failure/videotape and simple failure conditions, possibly because of the autonomic correlates of distress. PMID- 8463952 TI - Being and feeling unique: statistical deviance and psychological marginality. AB - Two studies tested the hypothesis that people with culturally stigmatized and concealable conditions (e.g., gays, epileptics, juvenile delinquents, and incest victims) would be more likely to feel unique than people with culturally valued or conspicuous conditions (e.g., the physically attractive, the intellectually gifted, the obese, and the facially scarred). In Study 1, culturally stigmatized individuals with concealable conditions were least likely to perceive consensus between their personal preferences and those of others. In Study 2, they were most likely to describe themselves as unique and to make these self-relevant decisions quickly. Marginality is a psychological reality, not just a statistical one, for those with stigmatized and concealable "master status" conditions. PMID- 8463953 TI - [Tumor necrosis factor and AIDS]. AB - Human immunodeficiency virus (HIV), an etiologic agent of AIDS, belongs to lentivirus subfamily of retroviruses. In striking contrast to oncoviruses HIV does not transform cells but instead causes chronic progressive diseases. This feature is demonstrable in vitro by dramatic cytopathic effects upon virus/cell coculture. Since virus-producing cells are generally destroyed, HIV must be transmitted to other cells after replication in order to maintain the infection. However, after viral infection, AIDS requires a long period of time before becoming full-brown. The virus appears to establish latent infection and stay dormant in many cells until activation signals have been received. We found that tumor necrosis factor can activate such latent HIV and selectively kill HIV infected cells. The mechanism of cell death was recently cleared as Apoptosis. PMID- 8463954 TI - [Chemical modification of nucleic acids and the mutagenicity of modified bases, with special reference to permanganate- and bisulfite-mediated modifications]. AB - Methods for modifying nucleic acids and their components with permanganate and with bisulfite are reviewed, with emphasis on work developed by the author's group of investigators. N(4)Aminocytidine, a nucleoside analog obtainable on bisulfite-hydrazine modification of cytidine, is a potent mutagen, and the mechanism of its action in the mutagenesis is discussed. PMID- 8463955 TI - [Synthesis of thiazolo[3,2-a]pyridine derivatives and their reactions]. AB - By the reaction of 2-benzoylmethyl-4-methylthiazole (6) with polarized olefins (3, 4) in the presence of base (K2CO3 or NaH), the corresponding thiazolo[3,2 a]pyridine derivatives (7, 8) were obtained. Methylsulfinylthiazolopyridine derivative (11) obtained by the reaction of 8b with m-chloroperbenzoic acid (MCPBA), easily underwent nucleophilic substitution to give the corresponding substituted compounds (10, 12). PMID- 8463956 TI - [Studies on as-triazine derivatives. XIX. Synthesis of 2,3-diarylpyrazine 2,3 diarylpyridine derivatives as blood platelet aggregation inhibitors]. AB - 4,5-Diphenyl-2-ethoxypyrimidine (1), 3,4-diphenyl-6-ethoxypyridazine (2) and 2,3 diphenyl-5-ethoxypyrazine (3) were evaluated for inhibitory activity towards arachidonic acid-induced aggregation of rabbit blood platelet in vitro. 2,3 Diphenyl-5-ethoxypyrazine (3) exhibited significant inhibitory activity. Thus, various 5-substituted 2,3-bis(4-methoxyphenyl)pyrazines were synthesized by the nucleophilic substitution reaction of 5-chloro-2,3-bis(4-methoxyphenyl)pyrazine (9). In a similar manner, substituted 2,3-bis(4-methoxyphenyl)pyridines were prepared from 2,3-bis(4-methoxyphenyl)-6-methylsulfonylpyridine (17), which was synthesized by the cycloaddition retro Diels-Alder reaction of 5,6-bis(4 methoxyphenyl)-3-methylsulfonyl-1,2,4-triazine (16) with norbornadiene. Among the compounds prepared, 6-isopropoxy-2,3-bis(4-methoxyphenyl)-pyrazine (10f) showed the most potent inhibitory activity, which was more than the activity of anitrazafen[5,6-bis(4-methoxyphenyl)-3-methyl-1,2,4-triazine. PMID- 8463958 TI - [Comparative studies on concentration of berberine in plasma after oral administration of coptidis rhizoma extract, its cultured cells extract, and combined use of these extracts and glycyrrhizae radix extract in rats]. AB - The present study was carried out to evaluate the bioequivalence between Coptidis Rhizoma and the cultured cells of Coptis japonica Makino var. dissecta Nakai to compare the concentration of berberine in the rat plasma after oral administration of both aqueous extracts. The concentration of berberine in the plasma after oral administration of both extracts was determined by HPLC. It was found that the values of time required for the maximum concentration (Tmax), the maximum concentration (Cmax) and the area under the plasma-time curve (AUC24h) of berberine in the rat plasma after oral administration of both extracts were about the same. It was also found that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts and an aqueous extract of Glycyrrhizae Radix were about the same as that of individual administration of both extracts. From these results, to evaluate the bioequivalence between Coptidis Rhizoma and cultured cells, it is important that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts are not different, and about the same values of berberine by the combined use of both extracts and the aqueous extract of other crude drugs are required. PMID- 8463957 TI - [A new lupin alkaloid, (-)-leontalbinine N-oxide, in Sophora flavescens var. angustifolia seeds and its synthesis by biomimetic transformation from (+) matrine N-oxide]. AB - The possibility of the biomimetic transformation of (+)-matrine N-oxide, a main alkaloid in Sophora flavescens var. angustifolia, under various oxidative conditions was examined by the use of several metallic ions. When (+)-matrine N oxide was warmed with FeSO4, or Fe(COOH)2 in MeOH-H2O at 40 degrees C, (-)-7, 11 didehydromatrine [(-)-leontalbinine], a minor alkaloid in the same plant, was obtained along with (+)-matrine. This selective formation of (-)-leontalbinine seems to be specific to the reaction of (+)-matrine N-oxide with ferrous reagents. In addition, the structure of the newly isolated minor lupin alkaloid from the seeds of S. flavescens. was determined as (-)-leontalbinine N-oxide from its spectral comparison with the authentic sample. PMID- 8463959 TI - [An oxidation enzyme for hydrogen sulfide from Hyphomicrobium neptunium ATCC15444]. AB - We described in our previous paper that the cell-free extract from Hyphomicrobium neptunium ATCC 15444 oxidized hydrogen sulfide to sulfur. We tried to purify the enzyme used for this oxidation to determine the molecular nature of this enzyme. The 40% ammonium sulfate precipitate from the supernatant of cell sonicate of H. neptunium was chromatographed on a column of Phenyl Sepharose CL-4B and its active fractions were collected. These fractions were further purified through Superose 12 and then TSK gel G3000SW column chromatographies. A protein of molecular weight about 54,000 and isoelectric point pI 6.8 was isolated. However, this final protein was found to reduce its activity to less than one-tenth of those of ammonium sulfate precipitate and of the fraction from Phenyl Sepharose CL-4B column chromatography. This might be caused either by the loss of accessory component or by its requirement of low molecular factors necessary for its activation at the stage of gel filtration. The neutral isoelectric point of this enzyme could be suitable as the function of H. neptunium because its final product was S0, and it grows at neutral pH. In contrast, the final oxidative product of hydrogen sulfide by Thiobascillus is sulfuric acid, and they grow at acidic pH. PMID- 8463960 TI - [Cyclosporine disposition in living related donor partial liver transplant recipients]. AB - We studied the disposition of cyclosporine (CyA) in 8 living related donor partial liver transplant recipients (patient A-H). CyA blood levels were determined by fluorescence polarization immunoassay with specific monoclonal antibody (m-FPIA) and fluorescence polarization immunoassay with non-specific polyclonal antibody (p-FPIA). The ratio of the blood levels of CyA determined by p-FPIA to those by m-FPIA varied significantly, because the levels determined by p-FPIA were influenced by the function of graft liver. Thus, the levels of CyA determined by p-FPIA could not be used for the adjustment of CyA dose. The CyA dose ratios [DR; CyA blood level (mg/l)/dose (mg/kg)] of 3 in 8 patients were relatively large in 1-4 d after the transplant operation, however, it decreased within 2-5 d after the operation. CyA DR gradually increased from 5-8 d after the transplantation, and it reached to a maximum in 10-13 d in 5 patients to whom CyA was administered intravenously over 12 d after transplantation. The average ratio of DR in oral administration to that in intravenous one was about 43%. CyA bioavailability in the patient of living related partial liver transplantation was as usual as that in other organ transplant patient except for cadaveric liver transplant patients. The average DR of intravenous CyA administration in liver transplant recipients was 1.5 times larger than that in bone marrow transplant patients. CyA disposition had large inter-individual and intra-individual variation, and CyA blood level and DR varied in clinical time course at least within 1.5 month after operation. Therefore, it is necessary to measure CyA blood level frequently and to adjust CyA dose. PMID- 8463961 TI - [Brainstem neural mechanisms of sleep and wakefulness]. PMID- 8463962 TI - Effect of adhesive metal primers on bonding a prosthetic composite resin to metals. AB - The effect of three adhesive metal primers on the shear bond strength of a light cured prosthetic composite resin bonded to cobalt-chromium or silver-palladium copper-gold casting alloy was evaluated. The adhesive metal primers used were New Metacolor opaque bonding liner, Cesead opaque primer, and 0.5% VBATDT in acetone. A newly prepared light-cured opaque resin was used to bond a light-cured veneering resin to dental alloys. The specimens were thermocycled in water for up to 20,000 cycles between 4 degrees C and 60 degrees C, and shear bond strengths were recorded. The light-cured composite resin bonded most strongly to Co-Cr alloy primed with Cesead primer and to Ag-Pd-Cu-Au alloy with the VBATDT primer. These adhesive metal primers may be clinically acceptable for bonding a light cured prosthetic composite resin to base or precious metal. PMID- 8463963 TI - Removable partial denture framework try-in. AB - Removable partial denture frameworks must fit accurately to function properly and not cause injury to remaining teeth or soft tissue. This article presents a logical method and rationale for seating a removable partial denture framework and a review of several disclosing media used in the try-in procedure. PMID- 8463964 TI - Radiographic and metallographic evaluation of porosity defects and grain structure of cast chromium cobalt removable partial dentures. AB - A study was undertaken to determine the defects in the internal microstructure of clasps of cast chromium cobalt removable partial denture frameworks. Ninety cast frameworks were radiographically evaluated for porosity with an industrial radiographic machine. The grain structure of the clasps was analyzed with an optical photomicroscope before and after various heat treatments. The radiographic study showed a large number of internal defects in various parts of removable partial denture frameworks. The grain structure study revealed microporosities randomly distributed within the matrix. Various heat treatments were performed and resulted in no change in the grain structure of the original castings. PMID- 8463965 TI - Tensile bond strength of maxillofacial adhesives. AB - A common technique for fixation of facial prostheses is the use of skin adhesives. The present study compared the tensile bond strength of five RTV silicone elastomers used with four different skin adhesives to human skin. The elastomers were: Silskin II, MDX4-4210, Cosmesil, Cosmesil HC2, and RS 330 T-RTV. The adhesives were: Dow Corning 355 medical adhesive, PSA 1, Daro, and 9874 3M double-coated medical tape. The RTV silicones were cured as described by the manufacturer, fixed in circular metal holders, and glued to the skin (inner aspect of forearm) with the various adhesives. The specimens were pulled off 20 seconds after fixation by use of a universal testing machine with a crosshead speed of 1 mm/minute. Eight specimens of each silicone and adhesive combination were tested, and a mean bond strength was calculated for each combination and compared by Duncan's multiple range test on a personal computer. Significant differences were observed among the various combinations of silicones and adhesives. Dow Corning 355 adhesive showed the highest bond strength with all materials, and the medical tape had the lowest. Differences between the RTV silicones were also significant. The strongest bond with all adhesives was MDX4 4210 elastomer and the weakest for RS 330 T-RTV elastomer. PMID- 8463966 TI - Orbital prosthesis with a magnetically retained ocular component supported by osseointegrated implants. AB - Positioning of the ocular component within an orbital prosthesis must simulate conversational gaze. Using osseointegrated implants and an associated superstructure, a fixed reference point can be established for positioning an ocular prosthesis. This method can simplify the laboratory procedure and obviate the need for ocular component repositioning in replacement prostheses. This article describes the fabrication of an orbital prosthesis with a magnetically retained ocular section supported by osseointegrated implants. PMID- 8463967 TI - CT scan as a radiologic data base for optimum implant orientation. AB - There are many factors directly related to the longevity of implant osseointegration. Overload has been considered an etiologic factor in implant failure after a prosthesis has been constructed. Optimum implant orientation can be aided by the three-dimensional radiographic data base provided by a CT scan. The reformatted sectional images, when related to each other, facilitate a thorough visualization of the bone topography, sinus and nerve location, and bone density. The fundamentals of the CT imaging and the interrelationship of the cross-sectional, panoramic, and three-dimensional reformatted images are described. PMID- 8463968 TI - Edentulous implants: overdenture versus fixed. AB - Implant restorations for edentulous patients may be planned as either fixed restorations or removable overdentures. Several factors should be considered when deciding between these treatment alternatives. They may be grouped into factors related to (1) the entire patient, (2) both arches, (3) maxillary restorations, and (4) mandibular restorations. PMID- 8463969 TI - Titanium alloy cylinders in implant framework fabrication: a study of the cylinder-alloy interface. AB - Titanium alloy has been proposed as a suitable alternative to noble metal alloys in premanufactured metal cylinders for fabricating implant prosthesis frameworks. The interfaces produced by standard lost wax procedures that use titanium and conventional noble metal implant cylinders with both high-fusing (high-palladium) and low-fusing (high-gold) noble metal casting alloys were compared. Elemental analysis by scanning electron microscopy and energy-dispersive spectroscopy (SEM/EDS) of the two titanium cylinders revealed that one commercial product had a composition similar to that for commercially pure titanium and the other had a composition consistent with that for Ti-6Al-4V alloy. The SEM observations and complementary elemental line scans indicated that the interfaces between the titanium cylinders and the two noble metal casting alloys did not meet proposed criteria for acceptable metal-to-metal unions. The interfaces between the noble metal cylinders and noble metal casting alloys did exhibit acceptable unions. The SEM observations and elemental analyses were supported by push-shear test results that showed that the resistance to failure was appreciably greater for interface specimens produced with alloy cast to noble metal cylinders compared with titanium cylinders. PMID- 8463970 TI - Adhesive abutment cylinder luting. AB - The connection between dental implants must be passive so that stress is not introduced between bone, implant, and prosthesis. To achieve this passivity clinically is difficult if not impossible with current procedures. A technique is presented in which premachined titanium abutment cylinders are clinically luted to a cast framework to create a stress-free connection. Possible advantages and disadvantages are discussed. PMID- 8463971 TI - Dental factors associated with temporomandibular joint sounds. AB - Dental factors commonly associated with signs and symptoms of temporomandibular disorders were investigated in a group of nonpatients. A highly sensitive technique was used to establish the presence of temporomandibular joint (TMJ) sounds. In a discriminant analysis nonworking side interferences, attrition, molar contacts, horizontal range of jaw movement, and morphologic occlusion contributed significantly to the prediction of sounds. Further study of morphologic aspects of the joint and stress-related parafunctions may contribute to the understanding of the development of TMJ sounds. We concluded that TMJ sounds are a fairly common sign associated with mild deviations in certain morphologic and functional aspects of the stomatognathic system. PMID- 8463972 TI - Biocompatibility: its future in prosthodontic research. AB - The future of prosthodontic research will involve replacing lost tissues by using scientific methods that evaluate biomaterials and treatment designs based on desired biologic outcomes. The present concept of a biocompatible material is one that elicits an appropriate host response in a specific application. To design optimal biomaterials, three interactive components should be considered: the chemical nature of the surface, the mediating pellicle layer, and microbial and host response. Surface chemistry determines which molecules are selectively absorbed onto a surface from oral fluids. The pellicle-coated surface should be designed to elicit a more desirable host response. Pellicle composition can be altered by chemically changing the surface, precoating surfaces with biological molecules, or using synthetic materials designed to mimic natural tissues. Several surface-sensitive techniques are available to assess these modifications, including vibrational spectroscopy, electron microscopy for chemical analysis, and bioanalytical methods. To develop more biocompatible materials, a further understanding of pellicle formation as a function of surface composition, microbial adhesion to biomaterials, and cellular reaction to implant biomaterials is necessary. This knowledge will facilitate development of new biologically based rationales for treatment modalities in restorative dentistry. PMID- 8463973 TI - Measurement of composite resin filler particles by using scanning electron microscopy and digital imaging. AB - Composite resins are routinely classified on the basis of filler particle size for purposes of research, clinical applications, and communications. The size and characterizations of filler particles have also been considered a significant factor in the rate of wear of composites. Making valid correlations between the filler particles within a composite and wear requires accuracy of filler particle size and characterization. This study was initiated to examine two methods that would (1) qualify the filler particle content of a composite resin and (2) quantify the number, size, and the area occupied by the filler particles in composite resins. Three composite resins, BIS-FIL I, Visio-Fil, and Ful-Fil, were selected as the materials to be examined, on the basis of their published composite classification type as fine particle. The findings demonstrated that scientific methods are available to examine qualitatively and measure quantitatively the composite resin filler particles in terms of their numbers, sizes, and area occupied by use of a scanning electron microscope and digital imaging. Significant differences in the filler particle numbers, sizes, and the area occupied were found for the three composite resins in this study that were classified as fine particle. PMID- 8463975 TI - Cytotoxicity of impression materials. AB - The purpose of this study was to assess the potential cytotoxicity of impression materials. The impression material brands tested included Impregum, Reprosil, Surgident, Permlastic, Jeltrate Regular and Jeltrate Fast Set. These impression materials and their components were tested for their possible cytotoxic effects by three different methods. The results showed that all impression materials were cytotoxic to some degree by all three assay methods and some of the components were also cytotoxic. These results support the literature showing in vivo adverse effects of certain impression materials and/or their components in patients and practitioners. PMID- 8463974 TI - Wear of ceramic inlays, their enamel antagonists, and luting cements. AB - The wear of ceramic inlay materials and antagonist enamel cups was measured in vitro. Per group, six MOD inlays were adhesively cemented in extracted molars. Castable glass ceramic, pressed glass ceramic, and feldspathic porcelain were used as inlay materials. A microfilled and a fine hybrid composite served as luting agents. The restorations were exposed to an in vitro wear test that corresponds to approximately 5 years of clinical service. The wear in the occlusal contact area was quantified during and at the end of the test with a three-dimensional scanner. Final wear measurements on the inlays (mean +/- SD) ranged from 21.8 +/- 8.8 microns for pressed glass ceramic to 59.0 +/- 37.9 microns for castable glass ceramic. The mean wear of the enamel antagonists ranged from 74.6 +/- 32.9 microns for pressed glass ceramic to 153.2 +/- 61.5 microns for feldspathic porcelain. The wear of the luting composites at the end of the test ranged from 4.9 +/- 5.1 microns for microfilled to 12.3 +/- 6.3 microns for fine hybrid. PMID- 8463976 TI - In-office fabrication of a claspless interim partial denture. AB - This article describes a technique for making a claspless interim removable partial denture that can quickly and easily be made in the dental office. The unnecessary undercuts are eliminated by use of a block-out putty without the need for duplication of the cast. The prosthesis can be inserted with minimum adjustments. PMID- 8463977 TI - Modification of angulated abutments to avoid unesthetic display of metal. AB - A procedure is described whereby the facial margin of angulated abutments are repositioned to avoid unesthetic display of metal in the anterior maxilla. The procedure is not difficult and can make a considerable difference in the patient's acceptance of the restoration. PMID- 8463978 TI - A .22 caliber die holding device. PMID- 8463979 TI - Shim stock placement for contact evaluation. PMID- 8463980 TI - Removal of partially or fully polymerized resin from porcelain veneers. PMID- 8463981 TI - Removal of resin-bonded fixed partial dentures. PMID- 8463982 TI - Use of the University of Barcelona gauge in the design of direct retainers. PMID- 8463983 TI - Spray-on technique for autopolymerizing acrylic resin. PMID- 8463984 TI - Simplified technique of recording edentulous jaw relationship. PMID- 8463985 TI - The retentive and stress distributing properties of split threaded endodontic dowels. PMID- 8463986 TI - Psychological disturbances and an exaggerated response to pain in patients with whiplash injury. AB - Psychological state, response to pain and style of interpreting everyday experiences were measured in 32 patients who had suffered a whiplash injury 1-84 months before the study. For comparison, measures were also obtained in 15 general practice attenders. Ratings of depression and anxiety were greater in patients than in controls, and patients reported more cold-induced pain during a cold pressor test. Within the patient sample, anxious subjects gave the highest ratings of cold-induced pain. Those with the longest history of pain gave the highest ratings of whiplash injury pain, and were most depressed. Most of these patients were involved in litigation. The findings demonstrate that, like most patients with chronic pain, whiplash injury sufferers are anxious and depressed. Their psychological distress could be aggravated by litigation. Behavioural assessment and treatment of chronic pain syndromes such as whiplash injury could benefit from early evaluation of the patient's psychological state, and response to standard painful stimuli. PMID- 8463987 TI - A psychological profile of endometriosis patients in comparison to patients with pelvic pain of other origins. AB - In order to investigate the possibility of a specific psychological profile associated with endometriosis, 81 women with pelvic pain were studied, of whom 40 were diagnosed as having endometriosis and 41 other gynaecological problems. Each patient completed six standardized psychometric tests to assess personality, psychopathology, marital state and pain. Endometriosis patients obtained higher psychoticism, introversion and anxiety scores in comparison to the other pain patients, although the two groups did not differ on pain ratings. Both groups obtained neuroticism, anxiety and psychiatric morbidity scores which were elevated relative to normative data. The possibility that there are certain psychological characteristics which make some women vulnerable to endometriosis is discussed. PMID- 8463988 TI - The prediction of somatic complaints using the Autonomic Nervous System Response Inventory (ANSRI) and the Daily Stress Inventory (DSI). AB - Understanding and prediction of veridical somatic complaints not caused by disease, dysfunction, trauma, or toxin, requires the assessment of at least two critical variables: predisposition to respond to stressors with peripheral physiological activation; and intensity/frequency/duration of stressors. The Autonomic Nervous System Response Inventory (ANSRI) and the Daily Stress Inventory (DSI) were used to assess these variables, and somatic complaints were recorded using the Wahler Physical Symptoms Inventory (WPSI). Subjects were 72 healthy undergraduates who completed the inventories and reported illness and medication usage over a 2 week period. Regression analyses showed that ANSRI, DSI, illness, and medication accounted for 35% of the variance in somatic complaints, though only ANSRI and DSI contributed significantly. Neuroticism (Eysenck Personality Questionnaire) did not add to R2, but did influence stressors' subjective impact. The correlation between regression equation generated WPSI scores (derivation sample) and actual WPSI scores (holdout sample) was 0.59. A discriminant function analysis equation (derivation sample) applied to the holdout sample correctly classified 80% of the upper and lower third WPSI subjects. It was concluded that the ANSRI and DSI, and the variables they assess, are substantially related to the self-report of somatic complaints. PMID- 8463989 TI - The effects of aerobic exercise on premenstrual symptoms in middle-aged women: a preliminary study. AB - The effects of aerobic exercise and strength training on premenstrual symptoms were evaluated in 23 healthy premenopausal women. Premenstrual symptoms were assessed at baseline and following 3 months of exercise participation. Women who engaged in aerobic exercise significantly increased their aerobic capacity, while the women who participated in non-aerobic exercise did not. Results showed that while participation in both exercise conditions was associated with general improvement in many premenstrual symptoms, subjects in the aerobic exercise group improved on more symptoms, especially premenstrual depression. PMID- 8463990 TI - Discrimination between psychogenic and organic erectile dysfunction. AB - The aim of this study was to develop a screening test based on the Leiden Impotence Questionnaire (LIQ) in order to assist in the difficult process of differentiating between psychogenic and organic erectile dysfunction (ED). The main sample consisted of 176 patients with ED, which was classified according to the results of the urological and psychiatric assessment as either organic, in 109 (62%) patients, or psychogenic, in 67 (38%) patients. A logistic regression model including six general items from the LIQ correctly identified psychogenic ED in 62% of the cases, and organic ED in 86%, with an overall correct classification rate of 76%. Adding information regarding sexual intercourse and the relationship in patients who had a partner and were having sexual intercourse the correct classification rates were: psychogenic 77%, organic 94%, and overall 87%. Discrimination between psychogenic and organic ED is improved when more information concerning sexual activity can be assessed. PMID- 8463991 TI - Development of a fatigue scale. AB - A self-rating scale was developed to measure the severity of fatigue. Two-hundred and seventy-four new registrations on a general practice list completed a 14-item fatigue scale. In addition, 100 consecutive attenders to a general practice completed the fatigue scale and the fatigue item of the revised Clinical Interview Schedule (CIS-R). These were compared by the application of Relative Operating Characteristic (ROC) analysis. Tests of internal consistency and principal components analyses were performed on both sets of data. The scale was found to be both reliable and valid. There was a high degree of internal consistency, and the principal components analysis supported the notion of a two factor solution (physical and mental fatigue). The validation coefficients for the fatigue scale, using an arbitrary cut off score of 3/4 and the item on the CIS-R were: sensitivity 75.5 and specificity 74.5. PMID- 8463992 TI - Restless sleep, illness intrusiveness, and depressive symptoms in three chronic illness conditions: rheumatoid arthritis, end-stage renal disease, and multiple sclerosis. AB - Restless sleep was compared across 110 out-patients with rheumatoid arthritis (RA), 101 with end-stage renal disease (ESRD), 94 with multiple sclerosis (MS), and an unselected control group of 176 individuals attending their family practitioners (FP). It was also investigated in the three chronic illness groups as a contributor to illness intrusiveness--the extent to which one's illness and/or its treatment interfere with continued involvements in valued activities and interests--a determinant of depression and emotional distress in chronic conditions. Reported frequencies of restless sleep were highest in RA, lower in ESRD, and lowest in MS; FP patients reported frequencies that were similar, overall, to those observed in MS. These differences were evident among nondepressed, (chi 2 9, N = 309, p < 0.0001), but not depressed, individuals. The occurrence of restless sleep correlated significantly with increased illness intrusiveness, r (279) = 0.31, p < 0.001, in RA, ESRD, and MS. Results supported the hypothesis that the relation between restless sleep and emotional distress is mediated by illness intrusiveness. Treatment of restless sleep may offer the added benefit of diminishing illness intrusiveness and may, thereby, enhance quality of life in chronic physical illness. PMID- 8463993 TI - Psychosocial factors associated with the early termination of breast-feeding. AB - The relation between a number of psychosocial factors and the early termination of breast-feeding was examined in two large independent samples of puerperal women. The findings were remarkably similar. In both cohorts there was a significant association with depressive disorder which in the great majority preceded the cessation of breast-feeding. Other factors of importance were low social class, being young and lower educational attainment. PMID- 8463994 TI - The impact of oral contraceptives on the experience of perimenstrual mood, clumsiness, food craving and other symptoms. AB - Two-hundred and seventy-six oral contraceptive (o.c.) users (171 combine o.c. and 105 triphasic o.c.) were compared with 276 non-o.c. users. All women regarded themselves as PMS sufferers, and the groups were matched for age, parity and marital status. Each woman rated severity of 27 symptoms during the premenstrual, menstrual and postmenstrual phases of their last menstrual cycle. The o.c. users reported significantly less menstrual pain and premenstrual breast tenderness. When controlling for the severity of premenstrual depression, there were no differences between the three groups in the timing or severity of perimenstrual food craving or clumsiness. When controlling for the severity of menstrual pain, the o.c. users showed significantly less improvement in negative mood during the menstrual phase, compared with non-users. The apparent tendency for o.c. users to show either a delayed or more prolonged pattern of perimenstrual negative mood deserves further study. PMID- 8463995 TI - Adult physical illness and childhood sexual abuse. AB - Recent interest has centred on the possible long-term physical effects of child sexual abuse. Research is now beginning to be carried out in this area. Some studies are portraying associations that are difficult to substantiate, as the methodological problems are considerable. This article attempts to summarize the literature to date and set some contexts for possible future research directions. PMID- 8463996 TI - Errors introduced in radioligand binding studies due to displaceable, cation dependent, [3H]prazosin binding to glass-fibre filters and glass surfaces. AB - [3H]prazosin not only specifically and homogeneously labels alpha 1 adrenoceptors, but also binds to glass surfaces and non-linearly to the glass fibre filters, commonly used in radioligand binding experiments. Binding to filters can be modulated by unlabeled alpha-adrenergic compounds and cations. If no correction is applied for displaceable filter binding, analysis of [3H]prazosin binding experiments leads to erroneous results. Analysis of [3H]prazosin saturation experiments on guinea-pig cerebral cortex membranes with correction for filter binding before the non-linear fit procedure indicated that [3H]prazosin labels a homogeneous population of alpha 1-adrenoceptors (Rtot: 8.33 fmol.mg-1 wet tissue) with a dissociation constant of 1.28 x 10(-10) M. However, analysis of the same data after correction for non-specific binding, (determined in parallel experiments by adding 10 microM phentolamine to the incubation medium) resulted in a best fit to a model in which [3H]prazosin labels two alpha 1-adrenoceptor subpopulations (R1: 15.0 fmol.mg-1 and R2: 14.6 fmol.mg-1 wet tissue) with dissociation constants of respectively 1.78 x 10(-10) and 5.63 x 10( 9) M. The discrepancy between the two methods of analysis is due to displacement of the radioligand from the filters by phentolamine. Prazosin and oxymetazoline are also able to displace filter-bound [3H]prazosin. The extent to which displaceable filter binding distorts the proper results depends on the actual magnitude of the error and also on the method of analysis. PMID- 8463997 TI - Characterization of [3H]SK&F 108566 as a radioligand for angiotensin type-1 receptor. AB - Rat aortic smooth muscle cells were used as a model system to characterize the binding properties of [3H]SK&F 108566, an angiotensin type-1 (AT1) receptor antagonist. The binding was specific, saturable and reversible. The association and dissociation rates of [3H]SK&F 108566 binding to smooth muscle cells were monophasic and Scatchard analysis of equilibrium binding data yielded a linear plot indicating a homogenous population of binding sites. The maximum binding (Bmax) and apparent dissociation constant (Kd) were 22,000 +/- 6000 sites/cell and 0.83 +/- 0.08nM respectively. The pharmacological specificity of [3H]SK&F 108566 binding to smooth muscle cells is consistent with that observed for AT1 and confirms AT1 receptor specificity of this radioligand. High affinity binding was observed in membranes prepared from bovine adrenal cortex, rat liver and rat kidney glomeruli. COS cells transfected with cDNA encoding human AT1 angiotensin II receptors also displayed high affinity binding site for [3H]SK&F 108566. No specific binding could be detected on membranes prepared from bovine cerebellum, a tissue rich in the angiotensin type-2 (AT2) receptor. These observations indicate that [3H]SK&F 108566 binds to sites which have pharmacological characteristics of angiotensin II AT1 subtype receptors and can be used as a subtype-selective radioligand to characterize AII receptors in various systems. PMID- 8463998 TI - Myasthenia gravis: effect on antibody binding of conservative substitutions of amino acid residues forming the main immunogenic region of the nicotinic acetylcholine receptor. AB - In Myasthenia Gravis most anti-acetylcholine receptor (AChR) antibodies are against a highly conserved area of the AChR alpha-subunit called the Main Immunogenic Region (MIR). Amino acid residues critical for MIR formation have been located within the sequence alpha 67-76. In the present study, binding of anti-AChR monoclonal antibodies (mAbs) to synthetic peptide analogues of the sequence alpha 67-76 of human and Torpedo AChRs containing conservative single residue substitutions identified the amino acid residues most important to the antigenicity of the MIR sequence, and offered clues to its tridimensional structure. Conservative substitutions of residues Asn68 and Asp71 greatly diminished mAb binding, identifying them as critical contact residues for anti MIR mAbs. Substitutions at Asp70 and Tyr72 moderately affected binding. Cross reactive mAbs originally raised against Electrophorus AChR bound single residue substituted synthetic peptides in a manner consistent with the possibility that Electrophorus AChR may have a glutamic acid residue at position alpha 70 or alpha 71. Substitutions at residues Asp/Ala70 and Val/Ile70 between human and Torpedo alpha-subunits may be size-compensating, suggesting these amino acids in the native AChR may be in closer proximity than proposed in previous models of the MIR. PMID- 8463999 TI - Stability of the sperm plasma membrane of hibernating bats (Myotis velifer) compared with other mammals. AB - Previous experiments have established that the long-lived spermatozoa of hibernating bats are resistant to the acrosome reaction and fertilization in vitro conventional techniques. We tested the hypothesis that the membranes of these spermatozoa are more resistant to perturbation than those of other mammals. We exposed them to non-specific bilayer destabilizing agents and abrupt changes in incubation temperature and tested their response by observing their status (motility and viability) after a time interval compared with other mammals (golden hamster, rabbit, human). The results did not support the hypothesis. The inherent longevity of bat spermatozoa may thus be a function of some component other than unique resilience of their plasma membrane. PMID- 8464000 TI - Protein content of rabbit embryos: one cell to peri-implantation blastocyst. AB - The protein content of rabbit embryos during the first 7 days of development in vivo was determined. The protein content of intact embryos, embryonic cells (intact embryos without mucin coats for developmental stages up to 96 h post coitum and free of blastocyst coverings for later stages) and blastocyst coverings were determined by the Pierce Micro BCA assay. The mean protein content of intact one-cell or two-cell embryos was 0.16 micrograms and increased at the four- to six-cell stage with no further increase until the late morula/early blastocyst stages (days 3 to 4). There was a 53-fold increase in protein from the early to late blastocyst stages. The protein content of embryonic cells was stable at a mean value of 0.16 micrograms until the late morula stage (day 3) and then increased to a mean of 6.85 micrograms on day 6 and 50.38 micrograms on day 7. The increase in protein content of intact embryos up to about 72 h appeared to be due solely to an increase in the protein content of the mucin coat. The protein content of the blastocyst coverings increased from a mean of 2 micrograms on day 5 to a mean of 35 micrograms on day 7. For blastocyst stages, the total protein content of intact blastocysts and of embryonic cells was correlated with the surface area of the embryos (r2 = 0.895 and 0.873, respectively) and, thus, an increase in blastocyst size is a true index of blastocyst development. PMID- 8464001 TI - Control of testicular vasomotion by testosterone and tubular factors in rats. AB - Testicular vasomotion (rhythmical variations in testicular blood flow) was studied in adult rats using laser Doppler flowmetry. Vasomotion was not present in testes in which the Leydig cells had been destroyed, but it could be induced by a low dose of testosterone. Transposition of a scrotal testis into the abdominal cavity inhibited vasomotion and this was apparently not caused by Leydig cell malfunction. Depletion of specific germ cells (by unilateral X irradiation induced killing of spermatogonia and maturation depletion of germ cells) did not abolish vasomotion in the testis. It is suggested that testicular vasomotion is influenced by testosterone and by factors from Sertoli cells. PMID- 8464002 TI - Active immunization of ewes against prostaglandin F2 alpha to control ovarian function. AB - The hypothesis that pregnancy success could be improved in early postpartum ewes by prolonging the lifespan of the corpus luteum via active immunization against prostaglandin F2 alpha (PGF2 alpha) was tested. Further experiments in ewes immunized against PGF2 alpha investigated the effects of exogenous PGF2 alpha on the preovulatory follicle and the effects of PGF2 alpha and oestradiol benzoate on corpus luteum function. Four weeks pre-partum, 39 ewes bred to lamb during seasonal anoestrus received either 5 mg PGF2 alpha-ovalbumin conjugate (n = 20; immunized) or ovalbumin (n = 19; control) in Freund's complete adjuvant. Treatments were repeated on day 5 post-partum with reagents emulsified in Freund's incomplete adjuvant. On day 17 post-partum, ewes received 500 iu pregnant mares' serum gonadotrophin (PMSG) and 48 h later 50 micrograms gonadotrophin-releasing hormone (GnRH). Laparoscopy was performed 36 h after GnRH to assess ovarian activity and ewes with recent ovulations were inseminated into the uterus. No immunized ewes had ovulated, but ten had follicles that luteinized and secreted progesterone during the 8 weeks studied. Eighteen of 19 control ewes ovulated and 15 of 18 had increased progesterone concentration for at least 21 days. By day 70 post partum, progesterone had returned to basal values in all control ewes. In a second study, 24 immunized ewes bearing persistent corpora lutea, and for which the interval from the previous parturition was greater than 90 days, received 15 mg PGF2 alpha and 500 iu PMSG followed 48 h later by 50 micrograms GnRH. PGF2 alpha induced corpus luteum regression in all ewes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464003 TI - Changes in pituitary secretion during the early postnatal period and anovulatory syndrome induced by neonatal oestrogen or androgen in rats. AB - The following experiments were performed: (i) concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin in plasma were measured at 2, 5, 8, 10 and 15 days in female Wistar rats treated on the first day of life with 100 micrograms oestradiol benzoate or vehicle; (ii) females injected on day 1 with 100 micrograms of oestradiol benzoate or 1 mg of testosterone propionate and from day 1 to day 10 or 15 with FSH and LH were killed on day 90; (iii) females injected from day 1 to day 10 or 15 with prolactin or vehicle were killed on day 90; (iv) females injected on day 1 with oestradiol benzoate and from day 1 to day 15 with a luteinizing-hormone-releasing hormone (LHRH) agonist were killed on day 90; (v) groups of females injected on days 1, 4, 7, 10, 13 and 16 with an LHRH antagonist were killed on day 90. Onset of puberty, vaginal cycles, organ weights and hormonal plasma concentrations were measured. Females treated on the first day of life with 100 micrograms oestradiol showed inhibition of gonadotrophin secretion and stimulation of prolactin secretion during the neonatal period. Females injected on the first day of life with oestradiol benzoate or testosterone propionate showed, in adulthood, anovulation, ovarian atrophy, reduced FSH plasma concentrations, increased prolactin plasma concentrations and reduced pituitary prolactin content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464004 TI - Role of the extracellular Ca2+ on the intracellular Ca2+ changes in fertilized and activated mouse oocytes. AB - Changes in intracellular calcium concentration ([Ca2+]i) in fertilized mouse oocytes were measured using the calcium-sensitive dye, fura-2. After fertilization, an initial long-lasting [Ca2+]i increase was followed by a periodic [Ca2+]i increase. The periodic increase in [Ca2+]i persisted for 1 to 3 h and all fertilized oocytes extruded the second polar body within 4 h. The mean interval of periodic [Ca2+]i increase was 470 +/- 180 s (mean +/- SD). The frequency of the periodic [Ca2+]i increase depended on the extracellular calcium concentration. Verapamil and nifedipine inhibited the periodic [Ca2+]i increase. Sixty-five per cent of tested cells extruded the second polar body within 90 min of exposure to 7% ethanol. In these activated oocytes, the long-lasting [Ca2+]i increase was observed. However, no cells showed a repetitive increase in [Ca2+]i. Both release of calcium from intracellular stores and influx of extracellular calcium contribute to the increase in [Ca2+]i induced by ethanol. We conclude that the extrusion of the second polar body requires an increase in [Ca2+]i above a certain threshold level and the mobilization of calcium of both the intracellular and extracellular space in mouse oocytes. PMID- 8464005 TI - Tdy-negative XY, XXY and XYY female mice: breeding data and synaptonemal complex analysis. AB - In this paper we have compared the breeding performance of Tdy-negative XY, XXY and XYY females to assess the relative importance of the lack of a second X chromosome compared with the presence of a Y chromosome, in reducing fertility. The XY females were of poor fertility, although five of twelve produced at least one offspring. The XXY females had larger, more frequent litters, and a longer reproductive lifespan, implicating the lack of a second X as the major cause of the poor fertility of XY females. Nevertheless, XYY females appeared to be more seriously affected than the XY females, suggesting that the presence of the Y may be a contributory factor. Pachytene analysis demonstrated that the Y is a very inefficient pairing partner for the X during female meiosis. In XY females only 11% of pachytene cells had the X and Y paired; in XXY females the two X chromosomes paired and the Y was almost always a univalent, while in XYY females the X paired with a Y in only 15% of pachytene cells. The presence of unpaired sex chromosomes has previously been implicated as a cause of oocyte loss during pachytene, and the proportion of cells with unsynapsed sex chromosomes decreased as pachytene proceeded, suggesting that they were progressively eliminated. Significantly, protection against elimination was afforded not only by synapsis between sex chromosomes, but also by self-synapsis if a sex chromosome remained as a univalent. It is concluded that sex chromosome univalence leading to pachytene oocyte failure is responsible for the postnatal oocyte deficiency seen in XY females. A separate study has shown that XXY females have a similar level of oocyte deficiency. It is suggested that the presence of a second X chromosome improves the fertility of XXY females, compared with XY females, by improving oocyte quality and by eliminating the production of lethal XY and OY zygotes. The genotype frequencies for the offspring of XY and XYY females differed from those predicted from the pachytene data. The XY females showed a marked deficiency of XO offspring compared with XXY and XYY aneuploid offspring, whereas the XXY females had fewer than expected XXY and XYY aneuploid offspring. PMID- 8464006 TI - Stimulation of release of beta-endorphin and oxytocin by prostaglandin F2 alpha in cattle at parturition. AB - Concentrations of beta-endorphin and oxytocin were measured in plasma of cows before, during and after parturition. The effect of the PGF2 alpha analogue cloprostenol on beta-endorphin and oxytocin release was investigated. During parturition, there were marked, parallel increases in beta-endorphin and oxytocin concentrations. Both hormones were released in an episodic manner in conjunction with uterine and abdominal contractions. It is therefore likely that factors stimulating oxytocin release also enhance beta-endorphin secretion. This suggests a role of labour or labour-associated hormones in stimulating peripheral beta endorphin release. Cloprostenol caused an immediate, pronounced increase in plasma beta-endorphin and oxytocin concentrations. PMID- 8464007 TI - Effects of progesterone and anti-progesterone RU486 on ovarian 3 beta hydroxysteroid dehydrogenase activity during ovulation in the gonadotrophin primed immature rat. AB - The effects of progesterone and RU486, a synthetic anti-progesterone, on ovarian 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, a key enzyme of progesterone production, were studied during ovulation in immature 22-day-old rats primed with pregnant mares' serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG). Ovarian 3 beta-HSD activities had increased significantly 4 h after hCG injection. These increases were inhibited at 4 and 6 h after hCG when 20 mg RU486 kg-1 was administered 2 h before hCG. However, RU486 had no influence on the activity of 3 beta-HSD when administered at the same time as hCG injection. A histochemical study revealed that 3 beta-HSD activities in the granulosa cell layer, but not in the theca cell layer, were inhibited when RU486 was given 2 h before hCG. Serum progesterone concentrations, but not oestradiol concentrations, were significantly suppressed by RU486 treatment 4 and 6 h after hCG. The effect of progesterone on ovarian 3 beta-HSD activity was tested by administering graded doses of progesterone exogenously to rats 2 h before hCG injection. Ovarian 3 beta-HSD activity was increased in a dose-dependent manner, and more than 20 mg progesterone kg-1 significantly stimulated the activity. Although 10 mg progesterone kg-1 did not stimulate ovarian 3 beta-HSD activities, the RU486-inhibited activities were recovered by the concomitant administration of 10 mg progesterone kg-1 with RU486. These results indicate that ovarian 3 beta HSD activity depends on progesterone concentrations, and suggest an autocrine regulation of progesterone production during ovulation in immature rat ovaries stimulated with PMSG and hCG. PMID- 8464008 TI - Inhibition of the acrosome reaction by trypsin inhibitors and prevention of penetration of spermatozoa through the human zona pellucida. AB - In this study we evaluated the effect of several trypsin inhibitors (p aminobenzamidine: pAB; N-alpha-p-tosyl-L-lysine-chloromethyl-ketone: TLCK and p nitrophenyl-p'-guanidino-benzoate: NPGM) on sperm binding and penetration of the human zona pellucida. Motile spermatozoa, selected by a two-step Percoll gradient, were incubated at 1 x 10(7) cells ml-1 at 37 degrees C and in 5% CO2 for 4.5 h. This was followed by the addition of 1 mmol pAB l-1 or phosphate buffered saline (control) for 30 min. Three to four non-viable human oocytes were then added to each sperm suspension and incubated for 3 h. The numbers of spermatozoa bound to the human zona pellucida and in the perivitelline space were determined by phase contrast microscopy. The results showed that pAB significantly inhibited zona penetration by spermatozoa (56 +/- 8% oocytes penetrated, control versus 0 +/- 0% oocytes penetrated, pAB, mean +/- SEM), without modifying spermatozoa-zona pellucida binding. The inhibition of zona penetration was due to a block of the acrosome reaction normally induced by the human zona pellucida. In separate experiments, sperm suspensions pretreated with 1 mmol pAB l-1 or 10 mumol NPGB l-1 exhibited a marked decrease in the percentage of acrosome reactions on the zona surface (85 +/- 4% and 76 +/- 3% inhibition, respectively). In addition, the inhibitors prevented the acrosome reaction induced by human follicular fluid (percentage of acrosome-reacted spermatozoa: control 8 +/- 2; follicular fluid 25 +/- 3; pAB 6 +/- 2; NPGB 8 +/- 1; TLCK 12 +/ 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464009 TI - Hormonal control of proteins synthesized and secreted by guinea-pig endometrium. AB - The amounts of protein synthesized and secreted (as indicated by [3H]leucine incorporation) by guinea-pig endometrium cultured for 24 h increased 2.1-fold between days 7 and 15 of the oestrous cycle. This increase did not occur if the guinea-pigs were pregnant. In ovariectomized guinea-pigs, oestradiol acting on a progesterone-primed uterus was the optimum stimulus for the maximum increase in endometrial protein synthesis and secretion. The two main proteins synthesized and secreted by day-15 guinea-pig endometrium had molecular masses of 99.8 and 192.1 kDa as determined on Sephacryl S-200HR. The production of the 99.8 kDa protein increased 5.2-fold between days 7 and 15 of the cycle. The 192.1 kDa protein was not detected in secretions produced by day 7 endometrium, and the 99.8 and 192.1 kDa proteins were not detected in secretions produced by day-15 pregnant endometrium. In ovariectomized guinea-pigs, progesterone did not stimulate the synthesis of secreted proteins of molecular masses above 77 kDa. Oestradiol stimulated the synthesis of secreted proteins with molecular masses of 87.8 and 192.1 kDa. However, oestradiol acting on a progesterone-primed uterus stimulated the synthesis of the secreted proteins with molecular masses of 99.8 and 192.1 kDa, which indicates that this combination of steroid hormones may be responsible for the increase in production of these two proteins by the day-15, nonpregnant guinea-pig endometrium. This stimulation by ovarian steroids of the synthesis and secretion of the 99.8 and 192.1 kDa proteins by the guinea-pig endometrium is apparently inhibited during early pregnancy. PMID- 8464010 TI - Ultrastructural changes of oocyte and follicular wall during oocyte maturation in the Japanese quail (Coturnix coturnix japonica). AB - This study examined structural changes in oocyte and follicular wall during oocyte maturation in Japanese quails. The structures of the germinal disc and the surrounding follicular wall were observed by light and electron microscopy 25, 6 and 1 h before the expected time of ovulation. The germinal disc of the oocyte was located near the oocyte plasma membrane at 25 h before ovulation, and the germinal vesicle was located in the centre of the germinal disc. Numerous cytoplasmic elements, such as elongated membrane-bound vesicles, mitochondria and glycogen granules were also observed in the germinal disc. The surface of the oocyte made close contact with the cytoplasmic processes of the granulosa cells. Six hours before ovulation, fluid filled spaces formed between the oocyte and follicular wall. At 6 h before ovulation, the germinal disc was similar to that at 25 h before ovulation, whereas the oocyte and the granulosa cells were disconnected. Myelin bodies and dense bodies developed in the cytoplasmic processes of the granulosa cells, suggesting that lysosomal enzymes were activated. In the follicle at 1 h before ovulation, the second maturation spindle was located just beneath the surface of the oocyte, and the first polar body was in the perivitelline space. In the germinal disc, the membrane-bound vesicles were swollen and well developed. We suggest that, during the process of early oocyte maturation, the junctions between the oocyte and granulosa cells are disconnected, and factors that promote oocyte maturation may be activated in the germinal disc since the membrane-bound vesicles are developed. PMID- 8464011 TI - Regulation of dominant follicle turnover during the oestrous cycle in cows. AB - The effect of progestin and luteinizing hormone (LH) pulse frequency on dynamics of dominant follicle growth during the first follicular wave after oestrus was examined in non-lactating Holstein cows by ultrasonography. On day 8 of the cycle, cows (n = 8) received a luteolytic dose of prostaglandin F2 alpha (PGF2 alpha; 25 mg) and an ear implant of Norgestomet (6 mg). On day 18, cows were assigned to a crossover design in which the implants were retained (T1) or replaced with a new implant (T2). All implants were removed on day 23. After oestrus, cows underwent a normal intervening oestrus cycle. On day 8 of the third cycle, T1 and T2 were reversed among cows. Ultrasonography and blood sampling were performed on alternate days throughout the experiment. On days 10 and 19 of the third cycle, blood was sampled every 15 min for 8 h in concert with an additional control group (n = 3) sampled on day 10 of the cycle. Progesterone concentration on day 8 before PGF2 alpha was 6.5 +/- 0.5 ng ml-1. Dominance of the first wave dominant follicle was extended beyond day 18 in 15 of 16 cows for T1 and T2 periods. The original dominant follicle ovulated in five of eight T1 and none of eight T2 periods (P < 0.01). New dominant follicles were detected on day 24 +/- 1 in T1 (n = 3) and on day 20.6 +/- 1 in T2 (n = 8; P < 0.01) cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464012 TI - Endocrine profiles and follicular development in early-weaned postpartum beef cows. AB - This study investigated whether treatment with progestagen, which improves fertility after early weaning in postpartum cows, altered concentrations of gonadotrophins or development and function of follicles. Patterns of luteinizing hormone (LH), oestradiol and follicle-stimulating hormone (FSH) and of follicular growth before first postpartum ovulation were compared in two experiments. At 17 to 25 days post partum, suckled anoestrous beef cows received an ear-implant containing 6 mg progestagen (norgestomet) for 9 days or served as untreated controls. Calves were weaned from all cows 7 days after initiation of treatment. Cows were observed for oestrous behaviour twice a day until 10 days after weaning. As expected, the proportion of anoestrous cows that formed a corpus luteum with a normal lifespan was greater (P < 0.01) in cows treated with norgestomet (Expt 1, 17 of 24; Expt 2, 18 of 22) than in control cows (Expt 1, 2 of 16; Expt 2, 3 of 18). In general, patterns of secretion of LH and oestradiol and of final growth of the preovulatory follicle did not differ between control and norgestomet-treated cows. However, there was a transient rise in FSH in association with weaning in control cows that did not occur in norgestomet treated cows. In addition, mean LH increased more rapidly and mean oestradiol was higher during the 3 days immediately before the preovulatory surge of LH in the norgestomet-treated cows (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464013 TI - Potential synergism between platelet-activating factor and alpha 1-recombinant interferon in promoting luteal maintenance in cyclic ewes. AB - In sheep, the presence of an embryo in utero on the 12th to 13th day after oestrus prevents luteolysis. These studies investigated whether platelet activating factor (PAF) could exert an antiluteolytic function, either alone or in combination with interferon. The intrauterine administration of 250 micrograms PAF per horn per day, administered through indwelling cannulae into the uterus as injections twice a day (n = 12) or by continuous infusion (n = 4) failed to extend luteal function compared with controls (n = 8). When indwelling cannulae were used to administer (i) 125 micrograms PAF per uterine horn, as a bolus infusion twice a day (n = 5), (ii) continuous infusion of 500 micrograms bovine recombinant alpha 1-interferon each day (brIFN, n = 5), (iii) 125 micrograms PAF per horn twice a day, plus 500 micrograms brIFN per day (n = 8), or (iv) vehicle (n = 5), the luteal phase was significantly longer in co-infused (iii) than in control (iv) animals. These findings indicate that pharmacological doses of PAF may act synergistically with interferons to prevent luteolysis. PMID- 8464014 TI - Active immunization of heifers against a synthetic fragment of bovine inhibin. AB - Two experiments were conducted in cyclic beef heifers to determine whether active immunization against bovine inhibin alpha 1-26 Gly-Tyr (bINH) affected follicular dynamics, hormone concentration or ovulation rate. In Expt 1, heifers (n = 9) were actively immunized against bINH conjugated to human alpha globulins (HAG) using bis-diazotized benzidine in non-ulcerative Freund's adjuvant (NUFA; primary on day 0; booster injections on days 53, 84 and 116 using conjugated bINH and on days 176 and 366 using unconjugated bINH; ten heifers were used as controls). Ovaries were examined daily using ultrasound scanning (days 70-155 and 384-391) and corresponding blood samples were collected for bINH antibody titre, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestradiol determinations. Four treated and four control heifers were injected with 10 micrograms gonadotrophin-releasing hormone (GnRH) on day 386 (day 2 of the oestrous cycle). Although bINH-immunized heifers had variable antibody titres ranging from 4 to 50% I125-labelled bINH bound to serum diluted 1:2000, ovulation rate was unaffected. In oestrous cycles with three dominant follicles, the ovulatory follicles grew faster (2.5 +/- 0.2 versus 1.6 +/- 0.3 mm day-1; mean +/ SEM), had shorter durations of growth (5.7 +/- 0.8 versus 9.6 +/- 1.6 days) and duration of detection (7.5 +/- 0.8 versus 12.0 +/- 2.4 days) in immunized heifers. Mean concentrations of FSH, LH and oestradiol were unaltered in most cases during oestrous cycles in bINH-immunized compared with control heifers. There was no significant difference in the percentage increase in FSH or LH, after GnRH injection, between control and immunized heifers. As ovulation rate was unaltered in the first experiment, a second similar study was designed using a different immunization protocol. In Expt 2, heifers were immunized with bINH conjugated to human serum albumin using glutaraldehyde with the following doses: 0.0 (control; n = 7), 0.33 (n = 7), 1.0 (n = 8) and 3.0 (n = 7) mg. Three booster immunizations were given 33, 66 and 209 days after primary immunization. Immunization increased the number of oestrous cycles with multiple ovulations (42 of 132 (32%) oestrous cycles examined) compared with controls (1 of 30 (3.3%) oestrous cycles examined). Neither titre nor ovulation rate was affected by dose of bINH used. In summary, following bINH immunization, ovulation rate was not increased despite changes in follicular dynamics in Expt 1, but was increased in 32% of oestrous cycles in Expt 2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8464015 TI - Effect of prenatal and postnatal photoperiod on spermatogenic development in the Djungarian hamster (Phodopus sungorus sungorus). AB - The effect of the pre- and postnatal daylength on the start of spermatogenesis and further testicular development from day 4 up to day 127 was investigated in Djungarian hamsters. Hamsters were either gestated under long (16 h light:8 h dark) photoperiod and reared under long or short (4 h light:20 h dark) photoperiod after birth (L/L and L/S hamsters, respectively), or gestated under short photoperiod and transferred to long photoperiod after birth (S/L hamsters). In L/L and L/S hamsters, spermatogenesis started between day 4 and day 5 (day of birth = day 1), when the first gonocytes entered the S-phase. A, Intermediate and B spermatogonia were first observed on days 6, 8 and 9, respectively. The proliferation pattern of gonocytes and Sertoli cells, studied between day 4 and day 9, did not differ between L/L and L/S hamsters. Hence, the duration of the postnatal photoperiod had no effect on the start of spermatogenesis. The first effect of postnatal photoperiod on spermatogenic development was observed on day 15, when testis weights and tubular diameters were reduced in L/S animals. From day 22 onwards, spermatogenesis was arrested mainly at the mid-pachytene stage, no tubular lumen was formed, and the number of preleptotene spermatocytes was reduced. The ultimate number of Sertoli cells per testis was not affected by postnatal short photoperiod. The duration of the prenatal photoperiod had a clear effect on spermatogenesis after birth. In S/L hamsters, the number of gonocytes per tubular cross-section was reduced on day 4 and 4.5. Gonocyte proliferation was reduced on day 5 and spermatogenesis started one day later. Consequently, A and Intermediate spermatogonia appeared on day 7 and 9, respectively. Sertoli cell proliferation was also shifted to later ages, but the ultimate number of Sertoli cells did not differ from L/L or L/S hamsters. From day 29 onwards, the number of preleptotene spermatocytes was increased in S/L hamsters, indicating that the Sertoli cells in these animals could support more germinal cells. In conclusion, a short postnatal photoperiod does not affect spermatogenesis before day 15 after birth, when further testicular development becomes arrested. A short prenatal photoperiod delays the start of spermatogenesis by one day, alters the proliferation pattern of Sertoli cells, and from day 29 onwards, enables the Sertoli cells to support more germinal cells. The duration of the pre- and postnatal photoperiod did not affect the ultimate number of Sertoli cells. PMID- 8464016 TI - Attenuation of antepartum relaxin surge and induction of parturition by antiprogesterone RU 486 in sheep. AB - Pregnant ewes were injected with either the antiprogesterone, RU 486 (4 mg kg-1 body weight, i.m.; n = 5), 3000 iu relaxin (i.m.; n = 9), or diluent (n = 8) at 12:00 h on days 144 and 145, to determine its effect on progesterone and relaxin secretion, and on induction of lambing. RU 486 induced earlier lambing (P < 0.01) compared with diluent treatment, but relaxin treatment did not significantly reduce the interval to parturition. Mean injection-lambing intervals were 31 +/- 2, 109 +/- 23 and 121 +/- 27 h for the RU 486, relaxin and diluent groups, respectively. There was no incidence of difficult birth (dystocia); all lambs were vigorous at birth; and placenta delivery was rapid (within 207 min) with RU 486 and relaxin treatments compared with diluent treated controls. Plasma progesterone concentrations averaged 11 ng ml-1 during the pretreatment period for all animals. RU 486 had a biphasic effect on progesterone concentrations, causing an initial increase (P < 0.05) within 2 h, and then an abrupt drop (P < 0.01) to 6 ng ml-1 by 18:00 h on day 145. Progesterone concentrations remained consistently lower (P < 0.05) in relaxin-treated ewes than in diluent-treated controls from days 144 to 147 and then began a steady decrease to 4 ng ml-1 on the day of parturition (days 149 and 150) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464017 TI - The effect of recombinant bovine somatotrophin on ovarian follicular growth and development in heifers. AB - The effects of recombinant bovine somatotrophin (BST) on the dynamics of ovarian follicular growth and development and peripheral insulin concentrations were investigated. Initially, studies were carried out in a population of Hereford x Friesian heifers to validate the ultrasound technique. In the first experiment, 12 heifers were injected daily with either 25 mg BST or vehicle for two oestrous cycles, and the effects on follicular dynamics and peripheral insulin were determined. In a second experiment, 12 heifers were given a single injection of 10 ml saline or 320 mg BST in a sustained-release formulation to examine the temporal relationships between growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin and the number of follicles. The validation studies demonstrated that small follicles (< 5 mm in diameter) could be clearly detected by real-time ultrasound, and that 75% (9 of 12) of heifers showed three waves of dominant follicle development during the oestrous cycle, whereas the remainder had only two waves. The changes in the numbers of follicles of the three size categories (< 5 mm, small; 5-10 mm, medium-sized and > 10 mm, large) also displayed a wave pattern similar to that of the dominant follicle, with a marked reduction in the number of subordinate follicles as the dominant follicle grew and reached its maximum size. In Expt 1, BST treatment increased the number of small follicles and caused a rise in peripheral insulin concentrations (P < 0.01) throughout the treatment period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464018 TI - Effect of immunization against synthetic peptide sequences of bovine inhibin alpha-subunit on ovulation rate and twin-calving rate in heifers. AB - Three peptide sequences from the bovine inhibin alpha-subunit (P1: 18-30; P2: 63 72 and P3: 107-122) were synthesized and conjugated to human serum albumin (HSA). Hereford cross-heifers (n = 5 per group) were injected with 3 mg of one of the peptide conjugates, followed by three booster injections at intervals of 11 weeks. Control heifers (n = 5) were injected with HSA only. Antibodies recognizing both the individual peptides and 32 kDa bovine inhibin were generated and ovulation rate was increased in peptide immunized heifers. In group P1, 1 of 5 heifers responded with an increased ovulation rate whereas in groups P2 and P3, 5 of 5 and 4 of 5 heifers, respectively, had an increased ovulation rate. In group P2, in the first oestrous cycle following booster injections 2 and 3, 4 of 5 and 3 of 5 heifers, respectively, responded with twin ovulations, whereas a fourth heifer had three ovulations following booster injection 3. After breeding following booster injection 3, 3 of 5 heifers in group P2 and 1 of 5 in group P3 gave birth to twin calves. This study demonstrates the potential of immunizing against synthetic peptide sequences of the alpha-subunit of bovine inhibin to increase ovulation and twinning rates in cattle. PMID- 8464019 TI - Comparison of follicular heterogeneity and ovarian characteristics in Meishan and large-white hybrid pigs. AB - Comparisons were made between characteristics of pre-ovulatory follicles recovered from prolific Chinese Meishan gilts (n = 12) and from European Large White hybrid gilts (n = 13) in the late follicular phase preceding their fifth oestrous cycle, to determine whether there is an ovarian basis for the enhanced prolificacy in the Meishan. A total of 177 follicles per breed was classified as pre-ovulatory, based on follicular fluid oestradiol concentrations. Results obtained demonstrated high variability in all follicular characteristics in both breeds and no decrease in heterogeneity was evident in the Meishan. The Meishan follicles tended to be smaller (P < 0.06) and had less follicular fluid (P < 0.005), but total oestradiol content per follicle was similar (P < 0.1) with the result that the concentration of oestradiol in follicular fluid tended to be higher (P < 0.06) in Meishan than Large-White hybrid pigs. There were no differences between breeds in terms of testosterone concentrations in follicular fluid, hCG binding to granulosa cells or total DNA content of granulosa cells. Concentrations of inhibin in follicular fluid were similar in both breeds (P > 0.1) which resulted in a trend towards less total inhibin content in Meishan than Large-White hybrid follicles (P = 0.065). Corpora lutea were recovered from both breeds (n = 12 per breed) on days 27-31 of pregnancy after mating at first, second and third oestrus:corpora lutea were smaller (P < 0.001) and contained less progesterone per corpus luteum in the Meishan (P < 0.05) than in Large White hybrid pigs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464020 TI - Activity of gonadotrophin surge-attenuating factor during the luteal phase in superovulated women. AB - Gonadotrophin surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that attenuates the luteinizing hormone (LH) surge in superovulated women. GnSAF bioactivity was studied during the luteal phase by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. In both cycles, the pituitary response to an acute intravenous injection (10 micrograms) of luteinizing-hormone-releasing hormone (LHRH) was investigated in late follicular (follicle size 16 mm), early luteal (day 5 after human chorionic gonadotrophin, hCG), midluteal (day 9 after hCG) and late luteal phase (day 12 or 13 after hCG). FSH was injected daily at the dose of 225 iu on cycle days 2, 3 and 4, and 150 iu thereafter. The increase in LH and FSH (mean +/- SEM) 30 min after LHRH in the spontaneous cycles decreased significantly from early to late luteal phase and remained unchanged in the FSH treated cycles. Increases in LH and FSH 30 min after LHRH were significantly attenuated in the FSH-treated compared with the spontaneous cycles in late follicular and luteal phases. Serum oestradiol and progesterone concentrations were significantly higher in the FSH than in the spontaneous cycles only in early, but not in mid- and late luteal phase. The pattern of serum oestradiol and progesterone changes during the luteal phase did not correlate with the increases in LH and FSH 30 min after hCG both in the spontaneous and the FSH cycles. These results suggest that GnSAF bioactivity is high during the luteal phase of superovulated cycles. PMID- 8464021 TI - Effect of indomethacin administered during the normal time of implantation on the progesterone and protein composition of plasma and uterine flushings of rabbits. AB - The present experiment was designed to investigate the mode of action of indomethacin, a prostaglandin synthesis inhibitor, as an antifertility agent, and to examine a possible effect of indomethacin administered during the normal peri implantation period on the protein content and progesterone concentration in plasma and uterine fluid in pseudopregnant rabbits. The results showed that treatment with indomethacin significantly reduced the plasma progesterone concentrations, decreased progesterone concentrations in uterine flushing, significantly decreased the total plasma proteins, and particularly decreased albumin in the plasma and in the uterine flushings. Uteroglobin production by the rabbit uterus was not affected by this treatment. It is concluded that the antifertility effect of indomethacin at the time of implantation is exerted by reducing progesterone concentrations in plasma and uterine fluid, possibly affecting steroidogenesis, and by reducing the percentage of albumin in plasma and in uterine fluid, probably by increasing renal excretion of albumin. These effects of indomethacin provide an environment within the uterus that would not support embryo implantation and development. PMID- 8464022 TI - Sensory cues and the suppression of reproduction in subordinate female marmoset monkeys, Callithrix jacchus. AB - Subordinate female marmoset monkeys remain anovulatory and have low plasma concentrations of luteinizing hormone (LH) when maintained with their dominant females. Olfactory cues from the dominant female have been implicated in maintaining this reproductive suppression. Subordinate females that received either ablation of the vomeronasal organ (an accessory olfactory organ; n = 3), ablation of the main olfactory epithelium (n = 4), or both lesions (n = 5) did not ovulate in the following 7 weeks while housed with their dominant female. Plasma LH concentrations following either or both lesions were similar to pre lesion concentrations. Olfactory lesions (verified by histological and behavioural trials) did not impair reproductive activity, as olfactory-lesioned dominant females underwent ovarian cycles of similar duration to intact dominant females. Lesioned subordinate females (n = 6), maintained in visual-only contact with their dominant female and group ovulated 29.1 +/- 9.3 days (mean +/- SEM) after physical separation from their dominant females; this first onset of ovulation was significantly delayed (P < 0.05) compared with intact subordinate females completely isolated from their dominant females and group (10.8 +/- 1.3 days, n = 8). Behavioural and visual cues together with olfaction all appear to play important roles in maintaining the suppression of ovulation in subordinate female marmoset monkeys. PMID- 8464023 TI - Testosterone response to a gonadotrophin-releasing hormone agonist in Hawaiian monk seals (Monachus schauinslandi). AB - Adult male Hawaiian monk seals were administered a gonadotrophin-releasing hormone (GnRH) agonist to determine its effectiveness in reducing the testicular production of testosterone. Blood samples were collected from four treated seals and two control seals at weekly intervals for 10 weeks and again at the beginning of the following breeding season. The GnRH-agonist had an initial, brief, stimulating effect on circulating testosterone, but this was followed by an inhibitory effect that lasted for 7 to 8 weeks. The plasma concentrations of testosterone were within normal ranges by the following spring. These results demonstrate a reversible form of long-term androgen suppression, which may have applicability in a variety of wildlife management programmes. PMID- 8464024 TI - Use of an oestrogen, androgen or gestagen as a potential chemosterilant for control of rat and mouse populations. AB - Three synthetic steroids were evaluated as potential chemosterilants for rodent control. Ethinyl oestradiol, methyl testosterone or Org 5933, a synthetic gestagen, were incorporated into paraffin blocks containing cereal grains and offered to laboratory rats and mice in addition to their standard laboratory diet. Ethinyl oestradiol (50 mg kg-1 paraffin block) was highly unpalatable to female rats, and the amount of steroid ingested was not sufficient to interfere with their oestrous cycles or inhibit ovulation. Methyl testosterone (5000 mg kg 1 paraffin block), although not as palatable as untreated blocks, was effective in inducing almost immediate infertility in female rats and mice at an ingested dose of about 35 micrograms g-1 body weight day-1. This infertility persisted throughout the duration of treatment, and lasted for several weeks after the cessation of treatment. Male rats became infertile after 3 months of treatment owing to suppression of spermatogenesis. Female rats developed a specific aversion to methyl testosterone when they were pregnant or lactating; it was therefore not possible to masculinize the brains of their female offspring. In mice, the androgen treatment induced high levels of aggression in the females so that they fought with males and with one another. One female died of her wounds. Org 5933 (4 mg kg-1 paraffin block) was highly palatable to female rats and mice, and at doses of about 420 ng g-1 body weight day-1 was effective in inhibiting ovulation in rats within 3 to 4 days after the start of treatment. This infertility persisted throughout the duration of treatment, and the animals conceived within 5 days of cessation of treatment. A dose of about 930 ng g-1 body weight day-1 was not completely effective in inhibiting ovulation in mice, but females that became pregnant during treatment gave birth to dead young. When the gestagen was given to female rats and mice in the last few days of pregnancy, the duration of gestation was significantly prolonged, and most young were born dead; some of the females also died in labour. The gestagen did not appear to inhibit lactogenesis, since the few animals that gave birth to live young reared them normally for the first 5 days of life. These results show that either methyl testosterone or Org 5933 in paraffin blocks could perhaps be used as a chemosterilant for the control of rat and mouse populations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8464025 TI - 1H nuclear magnetic resonance studies of seminal plasma from fertile and infertile men. AB - Glycerylphosphorylcholine (GPC), glycerylphosphorylethanolamine (GPE), citrate, and lactate content of human seminal plasma was analysed by measuring the peak area of 1H nuclear magnetic resonance (NMR) spectra in samples from four groups of patients: 21 spermatogenic failure subjects; 14 obstructive azoospermic subjects (vasectomized); seven patients presenting very severe oligoasthenozoospermia (OAT) and 18 normozoospermic subjects (control). The peak areas for GPC, citrate and lactate in seminal plasma were significantly smaller for patients with azoospermia than for the control group: 16.79, 8.18 and 2.28 versus 23.38, 10.58 and 4.30, respectively (P < 0.01). The peak area ratios for citrate:lactate and GPC:lactate were significantly different (P < 0.01) between the control group and the spermatogenic failure or obstructive azoospermia groups. A significant difference was also found in GPE:GPC peak intensity ratio between spermatogenic failure and obstructive azoospermia subjects (P < 0.001). These results provide some quantitative markers which may be used for examining infertility by using 1H NMR of seminal plasma samples. PMID- 8464026 TI - Effects of substrate supplementation with hydroxycholesterol analogues and serum lipoproteins on ovine luteal cell progesterone secretion in vitro: demonstration of prostaglandin F2 alpha luteolytic actions in a defined model system. AB - In an attempt to establish a defined model system for studies aimed at elucidating the mechanism of PGF2 alpha action, we examined the effects of medium supplementation with soluble hydroxycholesterol analogues, alone and in combination with ovine luteinizing hormone (oLH) in the presence and absence of PGF2 alpha, on progesterone secretion by mixed ovine luteal cells in vitro. In short-term cultures (2-6 h), supplementary 22R-hydroxycholesterol (22R-OHC; 0.16 20 micrograms ml-1) increased (P < 0.05) progesterone production in a dose dependent manner, whereas similar concentrations of 22S-hydroxycholesterol (22S OHC) and 25-hydroxycholesterol (25-OHC) had little effect. In incubations of < or = 24 h duration, 22R-OHC (1 micrograms ml-1) dramatically increased progesterone secretion, whereas oLH (100 ng ml-1) in the presence or absence of PGF2 alpha (250 ng ml-1) had no consistent effects, alone or in combination with 22R-OHC. In contrast, 22R-OHC (1 micrograms ml-1) alone had no effect in long-term incubations (72-192 h), nor did treatment with oLH (100 ng ml-1) in the presence or absence of PGF2 alpha (250 ng ml-1) in the absence of 22R-OHC. Together, however, 22R-OHC and oLH stimulated (P < 0.05) progesterone secretion, a synergistic effect consistently inhibited (P < 0.05) by PGF2 alpha. Equimolar (2.5 mumol l-1) concentrations of 22R-OHC and homologous serum low- or high density lipoprotein cholesterol exhibited comparable capacities to maintain progesterone secretion in long-term cultures (24-168 h), with and without gonadotrophin (oLH or human chorionic gonadotrophin, 100 ng ml-1) stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464027 TI - Effects of dilution procedure and culture conditions after thawing on survival of frozen bovine blastocysts produced in vitro. AB - Blastocysts derived from bovine zygotes fertilized and matured in vitro and cultured for 7 days in conditioned medium were frozen in 1.36 mol glycerol l-1 and 0.25 mol sucrose l-1. In vitro survival after thawing was unaffected by dilution rate in 0.25 mol sucrose l-1. The proportion of blastocysts that re expanded after 24 h was 81% (70 of 86) and 47% (33 of 70) hatched. Seven pregnancies beyond 2 months resulted from transfer of 21 blastocysts to 19 recipients. Total embryonic loss was 46.2%, of which 31% occurred between days 21 and 35. In vitro survival after thawing was influenced by culture conditions, the best being culture with oviduct epithelial cells, where 55-82% of blastocysts re expanded, of which 41-54% hatched. Conditioned medium also supported re expansion, but low hatching (6%), whereas M199 plus fetal calf serum allowed only limited re-expansion (19-40%). This behaviour was not a consequence of freezing. It is suggested that blastocysts produced in vitro have reduced metabolic activity leading to high embryonic loss before or just at the time of implantation and that oviduct cells create a favourable environment after thawing, allowing hatching in vitro. PMID- 8464028 TI - Seasonal fluctuation in diurnal rhythms of luteinizing hormone secretion in ewes during the mid-luteal phase of the oestrous cycle. AB - Diurnal and seasonal fluctuations were detected in luteinizing hormone (LH) interpulse interval, but not amplitude, in ewes examined during the mid-luteal phase of an oestrous cycle at five stages of the breeding season. Daytime and night-time LH interpulse intervals were greater in the early and late than in the mid-breeding season (P < 0.05). During the early and late breeding season, LH interpulse interval was less during daylight than during darkness (P < 0.05). Toward the mid-breeding season, interpulse interval decreased during daytime earlier in the season than the night-time decrease. It was concluded that the diurnal fluctuations observed are a component of a circannual rhythm in LH secretion resulting from gradual seasonal transitions in photoperiodic drive to, or an endogenous rhythm in, the hypothalamic-pituitary axis in ewes. PMID- 8464029 TI - Calmodulin-binding proteins in bovine semen. AB - An 125I-labelled calmodulin gel overlay procedure was used to direct calmodulin binding proteins in bovine spermatozoa and seminal plasma. Several calmodulin binding proteins with molecular masses ranging from 12 to > 200 kDa were detected in epididymal and ejaculated spermatozoa. Certain of these proteins exhibited preferential calmodulin-binding in the presence of Ca2+, while others exhibited binding only in its absence. In seminal plasma, only two major proteins with molecular masses of 15 and 16 kDa showed a higher calmodulin-binding activity in the presence of Ca2+, whereas several polypeptides in the range of 6-17 kDa bound higher amounts of radiolabelled calmodulin in the absence of Ca2+. Our previous study has shown that a group of closely related major proteins, designated as BSP A1, BSP-A2, BSP-A3 and BSP-30 kDa, isolated from bovine seminal plasma (BSP) have molecular masses in the range of 15-30 kDa. This prompted us to investigate whether these polypeptides from bovine seminal fluid interact with calmodulin. The results indicated that calmodulin binds to purified BSP-A1, -A2, -A3 and BSP 30 kDa proteins in the presence and absence of Ca2+. Furthermore, many polypeptides of low molecular mass (6-14 kDa) in bovine seminal plasma that crossreact with these BSP proteins also show high calmodulin-binding activity, particularly in the absence of calcium. This was further demonstrated following the limited proteolysis of the BSP proteins. Several tryptic-peptides of BSP-A1/ A2 and BSP-30 kDa exhibited higher calmodulin-binding activity than the intact BSP proteins. In view of the key role of Ca2+ in triggering the acrosome reaction and the role of calmodulin in intracellular transport of calcium, it is suggested that BSP proteins are involved in sperm capacitation and the acrosome reaction. PMID- 8464030 TI - Expression of interleukin 1, interleukin 6 and tumour necrosis factor alpha in mouse uterus during the peri-implantation period of pregnancy. AB - Interleukin 1 (IL-1), IL-6 and tumour necrosis factor alpha (TNF-alpha) are expressed in the mouse uterus on days 1-3 of pregnancy. Cytokine production is temporally associated with the post-mating intrauterine acute inflammatory response. In this study, IL-1, IL-6 and TNF-alpha were detected in the uterus of pregnant mice from day 3 to day 9, using northern blotting, bioassays and immunocytochemistry. IL-1 bioactivity increased from a low concentration on day 3 to a peak between days 4 and 5 and decreased to low concentrations on days 7 and 8. Blastocyst implantation occurs late on day 4. IL-6 bioactivity was high from day 3 to day 9 and activity was maximal on days 5 and 6. TNF-alpha bioactivity increased from its lowest concentration on day 3 to a peak on day 8. Although changes in bioactivity concentrations occurred at different times from changes in mRNA concentrations, the changes were approximately parallel. Translation of mRNA into an immunologically detectable product was confirmed using immunocytochemistry with polyclonal anti-cytokine antibodies. We conclude that the cytokines IL-1, IL-6 and TNF-alpha are produced in the uterus during the peri implantation period of pregnancy in mice. Changes in cytokine concentrations suggested the existence of some form of regulated expression. PMID- 8464031 TI - Control of peptides regulating mitosis of granulosa cells in immature rat ovary by oestrogen and gonadotrophin. AB - Previous studies in this laboratory have demonstrated the presence of a peptide that inhibits granulosa cell proliferation in medium sized follicles. This peptide was produced after 72-96 h of exposure to diethylstilboestrol (DES). This study analyses oestrogen and gonadotrophin modulation of this and another stimulatory peptide found in large follicles. Intact, immature, female rats were assigned to the following study groups: (i) one to four injections of DES (2 mg per rat) given at intervals of 24 h, animals killed 24 h after the last injection; (ii) DES at 0 and 24 h, animals killed 24 or 48 h after the last injection; and (iii) DES plus pentobarbital (37 mg kg-1 body weight) at 30 h, animals killed 48 h after the last injection. Small, medium and large follicles (diameters of < 200, 200-400 and > 400 microns, respectively) were isolated from ovaries, granulosa cells were harvested and follicular fluid supernatant (FFS) was collected. FFS proteins were tested for their effects on incorporation of [3H]thymidine into granulosa cell DNA. Results showed that unfractionated FFS protein (150 micrograms) from medium follicles in groups (i) (three and four injections only), (ii) and (iii) inhibited [3H]thymidine incorporation. Pentobarbital blockage of gonadotrophin secretion had no effect on the inhibitory peptide activity and two injections of diethylstilboestrol were enough to stimulate synthesis of the inhibitory peptide, provided sufficient time was allowed; FFS protein (150 micrograms) from large follicles was stimulatory, but only when it was collected 24 h after the second injection, and the effect was abolished with pentobarbital treatment. Fractionation of pooled FFS into proteins with three molecular mass ranges (< 10 kDa, 10-30 kDa and > 30 kDa) showed that the inhibitory activity was in the < 10 kDa fraction while the > 30 kDa fraction stimulated thymidine incorporation. The number of medium and large follicles increased 24 h after the second DES injection, but the number of granulosa cells in the large follicles was significantly reduced after pentobarbital blockage of gonadotrophins. Taken together, these findings show that (i) the inhibitory peptide is induced in effective amounts in the medium follicles 48 h after the second DES injection and induction is not modulated by gonadotrophins; and (ii) stimulatory activity seen in the large follicles is transient and under gonadotrophic control, since blockage of follicle-stimulating hormone (FSH) secretion led to loss of stimulatory activity and a resulting reduction in number of granulosa cells in large follicles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8464032 TI - Design, synthesis, and pharmacology of 3-substituted sodium azulene-1-sulfonates and related compounds: non-prostanoid thromboxane A2 receptor antagonists. AB - A series of novel azulene-1 carboxylic acid derivatives 28-30, azulene-1 sulfonic acid sodium salts 41a-c, and related compounds were synthesized. These compounds were tested for TXA2 receptor antagonistic activity. The inhibitory concentrations (IC50) of these compounds for vascular contraction (TXA2 tau receptor) and platelet aggregation (TXA2 alpha receptor) induced by (15S)-15 hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5(Z),13(E)- dienoic acid (U-46619) were obtained. Azulene-1-sulfonic acid sodium salts 41a-c were over 3 times more potent than azulene-1-carboxylic acids 28-30. The most potent compound, 41b was 4 orders of magnitude more potent than a TXA2 antagonist, BM13,177, in inhibiting vascular contraction (tau receptor) and had an IC50 of 9.0 x 10(-10) M. Compound 41b was also found to be a tau receptor selective antagonist (IC50 of contraction/IC50 of aggregation = 378) and to have no TXA2 synthetase inhibitory activity at concentrations up to 10(-4) M and no partial agonistic activity at concentrations up to 10(-5) M in rabbit aorta (tau receptor) and up to 10(-4) M in rabbit platelet-rich plasma (alpha receptor). In a radioligand binding assay using rabbit gel-filtered platelets, compound 41b had a high-affinity binding for the TXA2 receptor. In an in vivo study, compound 41b inhibited U-46619-induced sudden death in mice at a dose of 0.3 mg/kg and its duration of action was over 8 h when administered orally at 3 mg/kg. PMID- 8464033 TI - 7-Azetidinylquinolones as antibacterial agents. Synthesis and structure-activity relationships. AB - A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups. These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria. In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds. The influence on the structure activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied. Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work. 7-Azetidinyl-8-chloroquinolones were considered as warranting further development. PMID- 8464034 TI - Applications of neural networks in structure-activity relationships of a small number of molecules. AB - We investigated the applications of back propagation artificial neural networks (ANN) for a small dataset analysis in the field of structure-activity relationships. The derivatives of carboquinone were used as an example. It's been found that in this case the use of the same neural network results in unambiguous classification of new molecules. Predictions can be improved with statistical analysis of independent prognosis sets. We suggest that the sign criterion be used as a classification rule. We also compared neural networks with FALS and ALS in leave-one-out prediction. ANN applied to the same dataset has shown the same predictive ability as ALS but poorer than FALS. PMID- 8464035 TI - Synthesis and pharmacological evaluation of (nitrooxy)alkyl apovincaminates. AB - A series of (nitrooxy)alkyl apovincaminates has been synthesized and evaluated for their effects on vertebral and femoral blood flow. These derivatives were prepared from apovincaminic acid (4). In cerebral circulation, compound 5 (0.03 1.0 mg/kg iv) caused a dose-dependent increase in cerebral blood flow (CerBF) without affecting the blood pressure. It was more potent than vinpocetine (2). The structures of 2 and 5, determined by X-ray crystallography, showed differences in the electrostatic potential image and in the conformation of the ethyl group at the 16-position. PMID- 8464036 TI - Modeling of human thromboxane A2 receptor and analysis of the receptor-ligand interaction. AB - In order to elucidate the mode of the thromboxane A2 (TXA2) receptor-ligand interaction at the molecular level, a model for the human TXA2 receptor, a member of the G protein-coupled receptor family with seven transmembrane segments, was constructed on the basis of its amino acid sequence, which was determined recently (Hirata, M.; et al. Nature 1991, 349, 617-620). First, we made a model for the human beta 2-adrenergic receptor using its amino acid sequence and the known helix arrangement of bacteriorhodopsin. Then, a TXA2 receptor model was constructed based on the beta 2 receptor model and was used to analyze the receptor-ligand interaction. The ligand-binding pocket of the TXA2 receptor includes a serine residue from segment V, an arginine residue from segment VII, and a large hydrophobic pocket between these two residues. These results are consistent with the known properties of TXA2 and TXA2 antagonists having a hydrogen-bonding group such as hydroxyl, a carboxyl group, and a hydrophobic moiety. This model should be helpful for rational design of potent TXA2 antagonists. PMID- 8464037 TI - Uniformly modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides as nuclease-resistant antisense compounds with high affinity and specificity for RNA targets. AB - "Uniformly" modified phosphodiester or phosphorothioate oligonucleotides incorporating 2'-deoxy-2'-fluoroadenosine, -guanosine, -uridine, and -cytidine, reported herein for the first time, when hybridized with RNA afforded consistent additive enhancement of duplex stability without compromising base-pair specificity. CD spectra of the 2'-deoxy-2'-fluoro-modified oligonucleotides hybridized with RNA indicated that the duplex adopts a fully A-form conformation. The 2'-deoxy-2'-fluoro-modified oligonucleotides in phosphodiester form were not resistant to nucleases; however, the modified phosphorothioate oligonucleotides were highly nuclease resistant and retained exceptional binding affinity to the RNA targets. The stabilizing effects of the 2'-deoxy-2'-fluoro modifications on RNA-DNA duplexes were shown to be superior to those of the 2'-O-methylribo substitutions. RNA hybrid duplexes with uniformly 2'-deoxy-2'-fluoro-modified oligonucleotides did not support HeLa RNase H activity; however, incorporation of the modifications into "chimeric" oligonucleotides has been shown to activate mammalian RNase H. "Uniformly" modified 2'-deoxy-2'-fluoro phosphorothioate oligonucleotides afforded antisense molecules with (1) high binding affinity and selectivity for the RNA target and (2) stability toward nucleases. PMID- 8464039 TI - Synthesis and biodistribution of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate. A new ligand for the potential imaging of muscarinic receptors by single photon emission computed tomography. AB - 1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)- alpha phenylacetate (IQNP, 3), an analogue of QNB in which a phenyl ring has been replaced with an iodopropenyl substituent, was prepared and evaluated in vitro and in vivo for m-AChR selectivity and specificity. High specific activity [125]IQNP ([125I]-3) was synthesized in greater than 60% yield utilizing an electrophilic iododestannylation reaction with hydrogen peroxide for the oxidation of iodide. In in vitro receptor binding studies, 3 demonstrated high affinity for M1 (Ki = 0.78 nM), M2 (Ki = 1.06 nM), and M3 (Ki = 0.27 nM) subtypes. In vivo biodistribution studies in female rats [125I]-3 demonstrated high uptake in areas rich in muscarinic receptors such as the brain (cortex and striatum) and the heart. Blocking studies were performed with a series of receptor specific agents and demonstrated that the uptake of [125I]-3 was selective and specific for cerebral muscarinic receptor rich areas and that the binding to m-AChR is reversible. The high-yield preparation and specificity and selectivity of high specific activity [125I]IQNP for muscarinic receptors suggest that this is an attractive new agent for potential imaging of cerebral receptors using single photon tomographic imaging (SPECT). PMID- 8464038 TI - Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5 yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. AB - A series of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines+ ++ (7a-h) was synthesized for biological evaluation as selective agonists for M1 receptors coupled to phosphoinositide (PI) metabolism in the central nervous system. Each ligand bound with high affinity to muscarinic receptors from rat brain as measured by inhibition of [3H]-(R)-quinuclidinyl benzilate ([3H]-(R) QNB) binding. 5-(3-Methyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine+ ++ trifluoroacetate (CDD-0098-J;7a) displayed high affinity (IC50 = 2.7 +/- 0.69 microM) and efficacy at muscarinic receptors coupled to PI metabolism in the rat cortex and hippocampus. Increasing the length of the alkyl substituent increased affinity for muscarinic receptors yet decreased activity in PI turnover assays. The hippocampal PI response of 7a was blocked by lower concentrations of pirenzepine (8) or by higher concentrations of either AF-DX 116 (9) or p fluorohexahydrosiladifenidol (10), suggesting that at low concentrations 7a selectively stimulates PI turnover through M1 receptors. PMID- 8464040 TI - Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging. AB - It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4 fluorophenyl)tropane-2 beta-carboxylic acid methyl ester to primate caudate putamen was evaluated. The synthesis and binding affinity of 3 beta-(3,4- dichlorophenyl)tropane-2 beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated. PMID- 8464041 TI - In vitro cytotoxicity of GC sequence directed alkylating agents related to distamycin. AB - Imidazole containing analogues 7, 10, and 17 of distamycin wherein the C-terminus contain a dimethylamino moiety have been shown to selectively bind to the minor groove of GC-rich sequences. Accordingly, these agents were employed as vectors for the delivery of a variety of alkylating agents to GC-rich sequences. The alkylating agents are attached to the N-terminus of these vectors thus providing the benzoyl N-mustards (8, 15, and 18 that contain one, two, and three imidazole units, respectively) and substituted acetamides 11-14. Results from the ethidium displacement assay for the formamides 7, 10, and 17 and mustards 15 and 18 showed that these agents bind to calf thymus DNA, poly(dA.dT), poly(dG.dC), and also to coliphage T4 DNA, thus confirming their binding in the minor groove. The reduced binding constants of these compounds for poly(dA.dT) while still binding as strongly, or more strongly, to poly(dG.dC) than distamycin provided evidence for their acceptance of GC sequences. Selectivity for GC-rich sequences was also indicated by CD titration studies. Titration of 10, 15, 17, and 18 to poly(dA.dT) produced weak drug-induced CD bands at approximately 330 nm; however, interaction of these agents to poly(dG.dC) in equimolar drug concentrations gave strong bands in this region. Results from dialysis and cross-link gel experiments provided evidence of alkylation and cross-linking of DNA by the mustards which could explain their enhanced cytotoxicity over the formamido analogues. The bifunctional N-mustard-containing analogues 15 and 18 are significantly more cytotoxic than the monoalkylating acetamides 11-14. The mustards also exhibited significant activity against cell lines derived from solid tumors such as melanomas, ovarian cancers, CNS cancers, and small cell lung cancer. PMID- 8464042 TI - Adenosine-5'-carboxaldehyde: a potent inhibitor of S-adenosyl-L-homocysteine hydrolase. AB - Adenosine-5'-carboxaldehyde (3) and its 4'-epimer (4) were synthesized and shown to be potent type I mechanism-based inhibitors of recombinant rat liver AdoHcy hydrolase with k2/KI values of 16.7 x 10(-3) and 5.5 x 10(-3) nM-1 min-1, respectively. The observation that 3 and 4 are potent inhibitors of AdoHcy hydrolase supports the hypothesis that they function as key intermediates in the mechanism by which the (Z)- and (E)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosines 1 and 2 inactivate this enzyme. PMID- 8464043 TI - Position 2 and position 2/Ala15-substituted analogs of bovine growth hormone releasing factor (bGRF) with enhanced metabolic stability and improved in vivo bioactivity. AB - In order to prepare GRF analogs with high activity in vivo, a strategy was undertaken to stabilize the peptide to dipeptidylpeptidase IV (DPP-IV), a protease found in plasma which inactivates native human and bovine GRF by cleavage of the Ala2-Asp3 bond. Replacement of the Ala2 residue with Ser, Thr, or Gly in [Leu27]bGRF(1-29)NH2 resulted in peptides greatly stabilized against proteolysis in plasma, but having low inherent GH-releasing activity when tested in bovine pituitary cell cultures. Replacement of Gly15 with Ala15 was marginally effective in improving the in vitro bioactivity of this group of peptides. When tested for GH-hormone release in steers, however, the Thr2,Ala15 analog was four times more potent than bGRF(1-44)NH2. Eleven additional analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series were synthesized and evaluated for metabolic stability in bovine plasma and for GH releasing activity in steers in vivo and in rat pituitary cells in vitro. Two compounds, [Val2,Ala15,Leu27]dGRF(1-29)NH2 and [Ile2,Ala15,Leu27]-bGRF(1-29)NH2, had increased GH-releasing activity in steers over that of [Thr2,Ala15,Leu27]-bGRF(1-29)NH2 and over a previously reported super-potent analog, [desNH2Tyr1,D-Ala2,Ala15]-hGRF(1-29)NH2. PMID- 8464044 TI - Glycosylated derivatives of benzophenone, benzhydrol, and benzhydril as potential venous antithrombotic agents. AB - A series of glycosylated derivatives of benzophenone, benzhydrol, and benzhydril has been synthesized and evaluated for potential activity as venous antithrombotic agents. Studies on structure-activity relationships revealed that compounds having an electron-withdrawing group in the benzhydril or benzhydrol moiety, and specifically those having the beta-D-xylopyranosyl structure in the sugar moiety, were good antithrombotic agents in a rat model of venous thrombosis. PMID- 8464045 TI - Synthesis and biological activities of angiotensin II, Sarilesin, and Sarmesin analogues containing Aze or Pip at position 7. AB - Analogues of [Sar1]angiotensin II, Sarilesin (type I antagonist), and Sarmesin (type II antagonist) with L-azetidine-2-carboxylic acid (Aze) and L-pipecolic acid (Pip) at position 7 have been prepared by the solid-phase method, purified by reverse-phase HPLC, and bioassayed in the rat uterus. Analogues of the superagonist [Sar1]ANGII with Aze or Pip at position 7 and sarcosine (Sar) or aminoisobutyric acid (Aib) at position 1 had high intrinsic activity in the rat isolated uterus assay (34-184%). Analogues of Sarilesin ([Sar1,Ile8]ANGII) with Aze or Pip at position 7 and Sar or Aib at position 1 retained high antagonist activity (pA2 = 7.1-8.3). Analogues of Sarmesin ([Sar1,Tyr-(OMe)4]ANGII) with Aze and Pip at position 7 had pA2 values of 7.4 and 6.5, respectively. [Aze7]-ANGII and [Pip7]ANGII had low activities (12% and 1%, respectively), and deletion of Sar at position 1 of Sarmesin analogues abolished binding (or affinity) as judged from pA2 values. Nuclear Overhauser effect (NOE) spectroscopy studies of [Sar1,Aze7]ANGII in DMSO-d6 have indicated a clustering of the three aromatic rings (Tyr, His, Phe) and proximity of Sar C alpha and Arg C delta protons to the Tyr/Phe ring protons. These data emphasize that replacement of Pro with the lower and higher homologs Aze and Pip does not greatly alter the structural requirements necessary for expression of agonist or antagonist activity, when sarcosine occupies position 1, but not when Asp occupies position 1, suggesting that there is an intimate relationship between the N-terminal and penultimate residues of the molecule in the biologically active conformation of the molecule. PMID- 8464046 TI - Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate. AB - The syntheses and cytotoxic activities of substituted N-phenylacetamido derivatives of doxorubicin and melphalan are described. The derivatives were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates. N (Phenylacetamido)doxorubicin (2) and N-(phenylacetyl)melphalan (6) were found to be 10- and 20-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin and melphalan, respectively. When incubated with PGA, the cytotoxicity of 2 and 6 increased and became equivalent to that of the corresponding drugs from which they were made. The poor solubility characteristics of 2 in aqueous solutions provided the basis for the development of the more soluble doxorubicin derivatives, N-(4-aminophenylacetyl)doxorubicin (3) and N-(4-phosphonooxy)phenylacetyl)-doxorubicin (4). In vitro cytotoxicity assays indicated that 3 and 4 were at least 1000-fold less toxic than doxorubicin against H2981 cells. PGA and the mAb conjugate L6-PGA were able to effect the activation of 3 and 6 on H2981 cells (L6-antigen positive). Hydrolysis of the phosphate group of 4 was required prior to activation with PGA or L6-PGA. This was achieved using alkaline phosphatase, or by exposing 4 to phosphatases present in cell culture medium. The activation of 3, 4, and 6 on H2981 cells by L6-PGA occurred in an immunologically specific manner, since activation could be blocked by saturating cell surface antigens with L6 prior to treatment with L6-PGA. These results demonstrate that 3, 4, and 6 are prodrugs that can be specifically activated to release clinically approved anticancer agents by a mAb-PGA conjugate. PMID- 8464047 TI - Cyclic sulfolanes as novel and high affinity P2 ligands for HIV-1 protease inhibitors. PMID- 8464048 TI - Signal transduction by a 5-HT2 receptor: a mechanistic hypothesis from molecular dynamics simulations of the three-dimensional model of the receptor complexed to ligands. PMID- 8464049 TI - Significance of duplicated flagellin genes in Campylobacter. AB - The complex flagellum of Campylobacter coli VC167 contains two highly related (98%) flagellin subunit proteins which are produced from two 92% homologous, tandemly orientated genes, flaA and flaB. Mutants expressing only flaA form a full-length flagellar filament that confers slightly less than wild-type motility to the bacterium. However, flagellin mutants expressing only flaB produce extremely short, truncated filaments, and are only slightly motile. We have shown that the presence of two essentially identical genes is advantageous, in that flaAflaB+ mutants become highly motile upon passage by an event which allows the production of a full length simple flagellar filament containing a single FlaA FlaB chimeric flagellin protein. Furthermore, we have demonstrated that the reassortment of DNA that results in this chimeric protein can occur by two mechanisms: intragenomic recombination and transformation-mediated intergenomic recombination. PMID- 8464050 TI - Analysis of the backbone dynamics of interleukin-8 by 15N relaxation measurements. AB - The backbone dynamics of the cytokine interleukin-8, a symmetric homodimer of overall molecular mass 16 kDa, has been investigated at pH 5.2 by means of 15N relaxation measurements using heteronuclear two-dimensional inverse detected 1H 15N spectroscopy. 15N T1, T2 and NOE data were obtained for 66 out of a total of 67 backbone amide groups. The overall correlation time is 9.10(+/- 0.05) ns at 26.6 degrees C. All residues exhibit very rapid motions on a time-scale of < or = 20 ps. These very rapid motions alone can account for the 15N relaxation behaviour of 30 residues. The 15N relaxation data for another 21 residues can only be accounted for by the inclusion of an additional internal motion on a time scale ranging from 0.5 to 3.5 ns. These residues are clustered at the N and C termini, and in the loop regions connecting elements of secondary structures. Finally, the 15N relaxation data for another 15 residues could only be accounted for by the presence of chemical exchange on a time-scale ranging from approximately 170 ns to 2.25 ms. In addition, the inclusion of chemical exchange improved the fit to the experimental data for 10 of the 30 residues whose 15N relaxation behaviour could be accounted for by very fast motions alone. The residues exhibiting chemical exchange line broadening cluster at the interface of the long C-terminal alpha-helix and the underlying beta-sheet. It is suggested that this clustering is indicative of concerted rather than independent motions in regions of secondary structure, with motion at any one residue being propagated to neighbouring residues in van der Waals contact. PMID- 8464051 TI - Structural deviations at CpG provide a plausible explanation for the high frequency of mutation at this site. Phosphorus nuclear magnetic resonance and circular dichroism studies. AB - CpG sites in DNA are hotspots for mutations leading to human genetic disorders. However, the structural basis for these events were still unclear and necessitated a deeper evaluation. Our experiments with phosphorus-31 nuclear magnetic resonance, ultraviolet-melting and circular dichroism on two related CpG containing octanucleotide duplexes show that CpG is a malleable step whose conformation and thermal stability are strongly dependent on the nature of its flanking steps. We conclude that the CpG step may exert a deleterious structural influence on the helix very much like the mismatch containing steps. This peculiar property of CpG should constitute a molecular basis for its recognition by various ligands as well as for mutations affecting CpG and hence an explanation for its rarity in vertebrate genomes. PMID- 8464052 TI - Electron microscopy visualization of oligonucleotide binding to duplex DNA via triplex formation. AB - Using biotinylated oligonucleotides and streptavidin as a marker, we have visualized, with the help of electron microscopy, the triplex formation. We used the natural homopurine-homopyrimidine sequence from human papillomavirus 16 cloned within a plasmid. Under conditions favouring the formation of pyrimidine purine-pyrimidine triplex the corresponding pyrimidine oligonucleotide formed a complex with the insert and this complex was detected by electron microscopy. Similarly, under conditions favouring the formation of pyrimidine-purine-purine triplex the corresponding purine oligonucleotide formed a stable complex detected by electron microscopy. In both cases the complexes we observed exhibited remarkable sequence specificity. Near 80% of DNA molecules carried the streptavidin marker in the correct position and very few cases of non-specific binding were detected. We conclude that the triplex mode of recognition may provide very efficient sequence-specific markers for electron microscopy of DNA. PMID- 8464053 TI - Imaging frozen, hydrated acrosomal bundle from Limulus sperm at 7 A resolution with a 400 kV electron cryomicroscope. AB - Actin and scruin are present in a highly ordered array in the acrosomal bundle from Limulus sperm. Frozen, hydrated acrosomal bundle can be imaged in a 400 kV electron cryomicroscope using the spot-scan technique. Quantitative analysis of the h0l projection images shows diffraction data beyond 7 A. PMID- 8464054 TI - Comparison of the dynamics of an engineered insulin monomer and dimer by acid quenched amide proton exchange. Non-local stabilization of interchain hydrogen bonds by dimerization. AB - Dynamic differences between an engineered insulin monomer and dimer are investigated under physiological conditions by an adaptation of the method of acid-quenched amide proton exchange. Although exchange lifetimes of amide protons involved in intrachain hydrogen bonds are similar in the two analogs, dimerization specifically stabilizes two interchain hydrogen bonds (LeuB6-NH...O = C-CysA6 and CysA11-NH...O = C-GluB4) that are distant from the dimer interface. Such non-local stabilization demonstrates that fluctuations in the tertiary structure of the monomer are damped by dimerization. As the B6-A6 and A11-B4 hydrogen bonds are specific to the crystallographic T-state, their stabilization also indicates that the R-state (an allosteric feature of hexamer assembly) is not significantly populated in an isolated dimer. Our results are discussed in reference to recent hypotheses that crystal structures of insulin depict inactive conformers and that detachment of interchain contacts accompany receptor binding. PMID- 8464055 TI - Requirement for a disulfide bridge near the reactive site of protease inhibitor SSI (Streptomyces subtilisin inhibitor) for its inhibitory action. AB - The problem of why serine protease inhibitors having substrate-like structure around the reactive site are not degraded by the cognate protease has prompted us to investigate the structural requirements in Streptomyces subtilisin inhibitor (SSI) for its inhibitory action. We removed the disulfide bridge between Cys71 and Cys101 near the reactive site by oligonucleotide-directed mutagenesis, replacing both Cys residues with Ser residues. Inhibitory activity of the mutated SSI toward subtilisin BPN' was initially potent, but decreased remarkably with increasing incubation time after mixing (temporary inhibition), due to degradation of the mutated SSI by subtilisin via a specific intermediate with a nick at the reactive site (Met73-Val74). Binding affinity of subtilisin for the mutated SSI was reduced by more than 10(3)-fold, and the mutated SSI showed a 20 deg.C decrease in melting temperature, which probably mainly reflects the destruction of the region of alpha-helix containing Cys101. These results imply that the susceptibility of the mutated SSI to protease, and the irreversibility of the peptide bond cleavage at the reactive site, result from increased flexibility around the reactive site in the complex of the disulfide-bond-removed SSI with the protease, demonstrating the requirement of conformational rigidity around the reactive site of the inhibitor for its native inhibitory action. PMID- 8464056 TI - Evidence for a clustered genomic organization of FAX-zinc finger protein encoding transcription units in Xenopus laevis. AB - Finger associated box-zinc finger proteins (FAX-ZFPs) constitute a subfamily of the many C2H2 type ZFPs in Xenopus laevis. FAX is a highly conserved protein domain connected to variable zinc finger clusters. Three different FAX-ZFPs encoding genomic fragments were isolated and subjected to a detailed structural characterization. All three exhibit a common, highly conserved exon/intron organization, with the variant zinc finger clusters organized in a single exon for each gene analysed. Two of the three genomic fragments contain a second FAX ZFP encoding (partial) transcription unit each. Further evidence for a clustered organization of FAX-ZFP transcription units is provided by Southern blot analysis of large genomic restriction fragments separated by transverse field gel electrophoresis, and by in situ hybridization on intact chromosomes. Comparative sequence analysis of the genes isolated reveals an exceptional degree of DNA sequence conservation in both exon and intron regions in one part of the FAX encoding region, suggesting that recent gene conversion has led to the combination of these sequence elements with DNA segments including regions encoding variant zinc finger clusters. Overexpression of the FAX domain by itself or of a full-length FAX-ZFP in X. laevis embryos by means of mRNA injection does not interfere with the normal developmental program, suggesting general and not cell specific/regulatory functions for X. laevis FAX-ZFPs. PMID- 8464057 TI - Formation of a single base mismatch impedes spontaneous DNA branch migration. AB - DNA branch migration, a process whereby two homologous DNA duplexes exchange strands, is an essential component of genetic recombination. Models for homologous recombination have invoked spontaneous branch migration as one mechanism for the generation of large regions of heteroduplex DNA. During recombination, two homologous parental duplexes that contain similar, but not identical, sequences are paired and undergo strand exchange. An important issue is whether spontaneous branch migration is capable of traversing sequence heterology such as mismatches, insertions and deletions. We use a model four strand system to examine the effect of mispaired or unpaired bases on branch migration. The assay consists of annealing two short duplexes having defined sequence heterologies. Following annealing, a Holliday junction is formed that is free to branch migrate. Our results demonstrate that a single base mismatch, insertion or deletion is sufficient to pose a substantial barrier to spontaneous branch migration. In the presence of magnesium, branch migration through such sequence heterologies is almost completely blocked. Others have shown that non mobile four-way junctions undergo a dramatic shift in conformation in the presence of magnesium. Our data suggest that a similar transition occurs for the mobile Holliday junction. We also discuss how proteins may facilitate branch migration through sequence heterologies in vivo. PMID- 8464058 TI - Protein-DNA interactions of the mouse alpha A-crystallin control regions. Differences between expressing and non-expressing cells. AB - Genomic footprinting, in vitro footprinting and mobility shift assays were used to investigate the molecular basis for expression of mouse alpha A-crystallin, a major structural protein of the transparent lens of vertebrates. The putative control region of the mouse alpha A-crystallin gene was footprinted by DNase I digestion in nuclear extracts, by dimethylsulfate treatment in cultured cells, and by micrococcal nuclease digestion in isolated nuclei. The resulting digestion patterns were compared between alpha TN4-1 lens cells, which express alpha A crystallin, and L929 fibroblasts, which do not express alpha A-crystallin. Four regions of DNA were found occupied in both cell types. These included positions 111 to -97 (DE-1 region), positions -75 to -55 (alpha A-CRYBP1 region), positions -35 to -12 (TATA box and PE-1 region), and positions +23 to +43 (an AP-1 consensus sequence). The DNase I footprints of the DE-1 and alpha A-CRYBP1 regions, previously implicated as functional control elements, were substantially more pronounced using nuclear extract from the alpha TN4-1 cells than from the L929 fibroblasts, suggesting more stable protein binding with the former than with the latter. Numerous in vivo binding variations were noted between the two cell types in all four of the footprinted regions examined. Finally, two complexes (A and B) were formed specifically with nuclear extracts from the alpha TN4-1 cells and a synthetic deoxyoligonucleotide comprising the alpha A-CRYBP1 region. These data indicate that specific differences in protein-DNA interactions with putative control regions are associated with tissue-preferred expression of the mouse alpha A-crystallin gene. PMID- 8464059 TI - Phenyl-azide-mediated photocrosslinking analysis of Cro-DNA interaction. AB - Using phenyl-azide-mediated photocrosslinking, we show that the alpha carbon of amino acid 2 of the helix-turn-helix motif of bacteriophage lambda Cro is within 12 A of the bottom-strand nucleotides at positions 2 and 3 of the DNA half site in the Cro-DNA complex in solution. This result is in excellent agreement with the crystallographic structure of the Cro-DNA complex. The results of phenyl azide-mediated photocrosslinking analysis of Cro-DNA interaction, together with the previously reported results of phenyl-azide-mediated photocrosslinking analysis of CAP-DNA interaction, establish that phenyl-azide-mediated photocrosslinking is generalizable and provide information regarding the structural requirements for phenyl-azide-mediated photocrosslinking. Comparison of the results of phenyl-azide-mediated photocrosslinking to the results of EDTA: iron-mediated affinity cleaving indicates that phenyl-azide-mediated photocrosslinking yields superior resolution. PMID- 8464060 TI - Structural studies of the enveloped dsRNA bacteriophage phi 6 of Pseudomonas syringae by Raman spectroscopy. I. The virion and its membrane envelope. AB - We report and interpret the first Raman spectrum of a double-stranded RNA virus containing a membrane envelope. Spectra of the native bacteriophage phi 6 and of its isolated host-attachment (spike) protein and phospholipid-free core assembly were collected from aqueous solutions over a wide range of temperature. Comparison of the vibrational spectra by digital difference methods permits the following structural conclusions regarding molecular constituents of the fully assembled virion. (1) The double-stranded RNA, phospholipid and protein components of the phage exhibit Raman amplitudes in accordance with their biochemically determined compositions in the native virion (10, 20 and 70%, respectively). (2) alpha-Helix and irregular conformations are the dominant secondary structures in proteins of both the viral membrane and nucleocapsid. This represents a departure from previously examined icosahedral phage and plant viruses, which are dominated by beta-sheet structures. (3) The phospholipids of the viral membrane are liquid crystalline throughout the determined range of virus thermostability (0 to 40 degrees C). (4) The P3 spike protein of phi 6, which is anchored to, but not sequestered within the viral membrane, is largely alpha-helical (approximately 35%) and highly thermolabile. Denaturation of P3 at temperatures above 30 degrees C leads to appreciable loss (approximately 20%) of alpha-helix in favor of beta-strand structure, and alters significantly the environments of many aromatic side-chains. (5) The secondary structures of integral membrane proteins of phi 6 are overwhelmingly alpha-helical (approximately 70 to 80%) and also thermolabile. In contrast to P3, which exhibits aspartate and glutamate carboxyls in the ionized form (CO2-), the integral membrane proteins exhibit only protonated carboxyl groups (COOH). Treatment of phi 6 with butylated hydroxytoluene (BHT), which has been shown to remove the P3 spike protein, does not significantly perturb phospholipids and associated integral proteins of the viral membrane or structural proteins and packaged double-stranded RNA of the nucleocapsid. However, P3 subunits, which are recovered after BHT treatment, exhibit radically altered secondary and tertiary structures, including the loss of most subunit alpha-helices. Among the P3 side chains affected by BHT treatment, we note a general trend toward greater hydrophilicity and greater solvent exposure of the aromatic residues Trp and Tyr. On the other hand, the cysteine sulfhydryl groups of the BHT-isolated P3 monomer are not solvent exposed and function as strong hydrogen-bond donors in the protein core.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8464061 TI - Structural studies of the enveloped dsRNA bacteriophage phi 6 of Pseudomonas syringae by Raman spectroscopy. II. Nucleocapsid structure and thermostability of the virion, nucleocapsid and polymerase complex. AB - Structures and thermostabilities of the double-stranded (ds) RNA bacteriophage phi 6 and of its isolated nucleocapsid-polymerase complex (nucleocapsid core) and dsRNA components have been investigated by Raman spectroscopy. The spectra show that proteins of the phi 6 virion are collectively deficient in beta-sheet secondary structure. In particular, the major protein (P8) of the outer spherical shell of the phi 6 nucleocapsid exhibits a secondary structure dominated largely by alpha-helix and irregular conformations. The absence of appreciable beta structure in the P8 subunit suggests a tertiary conformation lacking the beta barrel motif common to subunits of most other spherical viral capsids. In addition, the Raman spectra show that subunits of the dodecahedral nucleocapsid core are also predominantly alpha-helical. The results thus indicate a largely alpha-helical secondary structure for the major subunit (P1) of the phi 6 nucleocapsid core, as well as for the P8 subunit of the outer spherical shell. Using Raman difference spectroscopy, we demonstrate that proteins of the nucleocapsid core (P1, P2, P4 and P7) interact extensively with the packaged phi 6 RNA genome, and further, that conformational stability of the packaged RNA is reduced upon removal from the core. Also, we find that proteins of the phi 6 nucleocapsid are significantly more thermostable than proteins of the viral membrane envelope, which are reported in the accompanying paper (Li et al., 1993). The present results suggest that both the architectural principles and modes of protein-RNA interaction in the phi 6 virion differ fundamentally from those of icosahedral single-stranded RNA viruses. Both Raman and circular dichroism spectra indicate that the dsRNA genome of phi 6 is an A-form structure. The Raman marker bands signify the presence only of C3'-endo/anti nucleoside conformers. The Raman signature of dsRNA, revealed in the spectrum of the phi 6 genome, is discussed here as a model for assessing base-pairing and base-stacking interactions in other ribonucleoprotein assemblies. PMID- 8464062 TI - Function of IHF in lambda DNA packaging. II. Effects of mutations altering the IHF binding site and the intrinsic bend in cosB on lambda development. AB - cosB is the binding site on lambda DNA for terminase, the phage DNA packaging protein. cosB contains three binding sites for gpNu1, the small subunit of terminase, and a site for integration host factor (IHF). IHF plays an accessory role in lambda DNA packaging, and IHF stimulates the burst size of lambda several fold, presumably by assisting the interaction of terminase with cosB. The present work includes a study of the effect on lambda development of a mutation, called I1A-, which consists of three adjacent base-pair changes in the IHF binding site. The I1A- mutation was found to abolish IHF stimulation of the lambda burst size, indicating that IHF is unable to bind to the mutant I1A site. A second mutation, called I1B- and also consisting of three adjacent base-pair changes, is a mutation that reduces an intrinsic bend found in cosB. lambda I1B- was more dependent on IHF than lambda+, raising the possibility that the intrinsic bend in cosB plays a role in cos function for lambda+ under the IHF- conditions. In vitro DNA packaging experiments established that the I1 mutations affect DNA packaging per se. A series of Nu1 mutations that create terminases able to suppress a variety of cosB defects were found to suppress the defects of the I1A- and I1B- mutations under IHF- conditions. PMID- 8464063 TI - Refined structure of the pyruvoyl-dependent histidine decarboxylase from Lactobacillus 30a. AB - The crystal structure of the pyruvoyl-dependent histidine decarboxylase from Lactobacillus 30a has been refined to an R-value of 0.15 (for the 5.0 to 2.5 A resolution shell) and 0.17 (for the 10.0 to 2.5 A resolution shell). A description of the overall structure is presented, focusing on secondary structure and subunit association. The enzyme is a hexamer of alpha beta subunits. Separate alpha and beta-chains arise from an autocatalytic cleavage reaction between two serine residues, which results in the pyruvoyl cofactor. The central core of the alpha beta subunit is a beta-sandwich which consists of two face-to-face three-stranded antiparallel beta-sheets, flanked by alpha-helices on each side. The beta-sandwich creates a stable fold that allows conformational strain to be introduced across an internal cleavage region between the alpha and beta chains and places the pyruvoyl cofactor in a position for efficient electron withdrawal from the substrate. Three alpha beta subunits are related by a molecular three-fold symmetry axis to form a trimer whose interfaces have complementary surfaces and extensive molecular interactions. Each of the interfaces contains an active site and a solvent channel that leads from the active site to the exterior of the molecule. The trimers are related by a crystallographic two-fold symmetry axis to form the hexamer with an overall dumbbell shape. The interface between trimers has few molecular interactions. PMID- 8464064 TI - Backbone-dependent rotamer library for proteins. Application to side-chain prediction. AB - A backbone-dependent rotamer library for amino acid side-chains is developed and used for constructing protein side-chain conformations from the main-chain co ordinates. The rotamer library is obtained from 132 protein chains in the Brookhaven Protein Database. A grid of 20 degrees by 20 degrees blocks for the main-chain angles phi, psi is used in the rotamer library. Significant correlations are found between side-chain dihedral angle probabilities and backbone phi, psi values. These probabilities are used to place the side-chains on the known backbone in test applications for six proteins for which high resolution crystal structures are available. A minimization scheme is used to reorient side-chains that conflict with the backbone or other side-chains after the initial placement. The initial placement yields 59% of both chi 1 and chi 2 values in the correct position (to within 40 degrees) for thermolysin to 81% for crambin. After refinement the values range from 61% (lysozyme) to 89% (crambin). It is evident from the results that a single protein does not adequately test a prediction scheme. The computation time required by the method scales linearly with the number of side-chains. An initial prediction from the library takes only a few seconds of computer time, while the iterative refinement takes on the order of hours. The method is automated and can easily be applied to aid experimental side-chain determinations and homology modeling. The high degree of correlation between backbone and side-chain conformations may introduce a simplification in the protein folding process by reducing the available conformational space. PMID- 8464065 TI - 1.8 A refined structure of the lipase from Geotrichum candidum. AB - A lipase from the fungus Geotrichum candidum is one of only three interfacially activated lipases whose structures have been reported to date. We have previously reported the partially refined 2.2 A structure of this enzyme. We have subsequently extended the resolution and here report the fully refined 1.8 A structure of this lipase. The structure observed in the crystal is apparently not the lipolytic conformation, as the active site is not accessible from the surface of the molecule. A single large cavity is found in the interior of the molecule and extends from the catalytic Ser to two surface helices, suggesting that this face may be the region that interacts with the lipid interface. The mobility of local segments on this face is indicated by temperature factors larger than elsewhere in the molecule and by the observation of several residues whose side chains are discretely disordered. These observations strongly suggest that this portion of the molecule is involved in interfacial and substrate binding, but the exact nature of the conformational changes induced by binding to the lipid interface can not be determined. PMID- 8464066 TI - Rotamers: to be or not to be? An analysis of amino acid side-chain conformations in globular proteins. AB - Originally, rotamers were defined as side-chain torsion (chi-angle) combinations corresponding to the local minima of potential energy (van-der-Waals and torsion terms) for the side-chain of a terminally blocked amino acid. If at least one chi angle differed by more than 20 degrees from that of a rotamer, the side-chain was considered as deviant both from energetic (increase in potential energy of no less than 1 to 2 kcal/mol) and geometric (precision of atom positioning is worse than 0.5 A) aspects. In this work the distribution of side-chain conformations in protein crystal structures is analysed. Large deviations from rotameric chi values occur systematically and cannot be attributed merely to errors in crystal structure determination. The "rotamericity" (the fraction of residues within +/- 20 degrees of the chi-angles of a rotamer) not only remains substantially below 100% (70 to 95% for various amino acids) with improving crystallographic resolution but actually decreases for 8 out of 17 amino acid types after a critical resolution limit is crossed. This effect has been observed for external as well as for internal residues. The set of amino acid side-chain conformations in globular proteins cannot be considered as normally distributed around some rotamer points. Outliers occur systematically. The rotamericity of an amino acid depends essentially on the different environments the amino acid meets in real protein structures. Factors such as the backbone torsion angles of the residue itself, the secondary structure and tertiary contacts influence the rotamericity. The deviations in regions of regular main-chain structure from the average g :t:g+ relationship in the chi 1-angle become much more evident if, in addition to the typical secondary structure assignments, the actual backbone torsion angles of the residue are taken into account. In alpha-helices the t:g+ distribution in the chi 1-angle correlates with physical properties describing volume, extension and flexibility of the side-chain. In beta-strands the factors influencing the t:g+ distribution in the chi 1-angle are the polarity and hydrophobicity of the side-chain. Nevertheless, a considerable number of residues do not comply with the statistical preferences observed for the side-chain conformation. Large deviations from the rotamer values are observed especially in cases when normally advantageous chi 1-values are not allowed and adjustments in chi 2 become necessary to accommodate the side-chain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8464067 TI - Crystal structure of the trigonal form of human plasma retinol-binding protein at 2.5 A resolution. AB - The three-dimensional structures of the liganded and unliganded forms of human plasma retinol binding protein (RBP) in the trigonal crystal form have been solved at 2.5 A resolution. The final model of RBP complexed with retinol (holoRBP, space group R3, a = b = 104.0 A, c = 74.4 A) has a crystallographic R factor of 0.176 for 9652 reflections. The unliganded form, obtained through a purification procedure which included steps based on hydrophobic interaction chromatography, crystallized isomorphously with holoRBP and its structure has been refined to an R factor of 0.190 for 9614 reflections. The structure of the trigonal holo protein is quite similar to that of the orthorhombic form: the root mean-square deviation of all the equivalent alpha-carbons in the two chains is 0.53 A. The structural comparison between the liganded and unliganded forms of RBP in the crystal did not reveal gross conformational changes. The most significant difference between the two forms of the protein is a conformational change involving residues from 34 to 37. In this region, the movements of side chains of Leu35 and Phe36 are most noticeable. In particular, in the unliganded form the side-chain ring of the latter residue is in the place previously occupied by the alcoholic moiety of retinol. Our data are consistent with a model in which a region comprising these residues and at least part of the opening of the beta-barrel is involved in the recognition between RBP and transthyretin. In the case of the unliganded form, the central cavity, that is occupied by the vitamin in the two human crystalline holoRBPs, is filled by electron density that, at the present resolution, we interpret as solvent. PMID- 8464068 TI - Solution structure of human plasma fibronectin under different solvent conditions. Fluorescence energy transfer, circular dichroism and light-scattering studies. AB - Human plasma fibronectin is a high molecular weight (530,000), multi-domain, modular glycoprotein, consisting of two nearly identical subunits disulfide bridged close to their C-terminal ends. Three sites that can be differentially labeled with fluorescent probes are present on each fibronectin subunit, the transglutaminase-sensitive Gln3 residue and the two free sulfhydryl residues, Cys1201 and Cys2196. These sites are located, respectively, in the N-terminal heparin/fibrin-binding domain, between the central DNA and cell-binding domains, and just before the C-terminal fibrin-binding domain. To map the relative spatial arrangement of these domains, steady-state and lifetime fluorescence energy transfer techniques were employed. Our results show that the minimal intramolecular distances between the labeled Gln3-Cys1201 and Gln3-Cys2196 pairs are 5.5(+/- 0.6) nm and 5.7(+/- 0.7) nm, respectively, as measured by steady state methods. Lifetime methods gave somewhat higher distances of 8.1(+/- 0.2) nm and 7.6(+/- 0.2) nm, respectively, between these sites. The binding of heparin or subjection to high ionic strength had only a minor effect, while in the presence of 50% (w/v) glycerol, an increase of about 25% in the intramolecular distances between these sites was observed. A similar effect was induced by binding of fibronectin to the surface of Cytodex beads, an event which was previously shown instead to markedly increase the intersubunit distances between the Gln3-Gln3 and Cys1201-Cys1201 pairs. The solution structure of fibronectin was further investigated by elastic light-scattering and circular dichroism measurements. By elastic light-scattering, the radius of gyration of fibronectin was found to be 15.3(+/- 0.8) nm in the presence of 30% (w/v) glycerol, in contrast to a value of 8.6(+/- 0.3) nm under physiological conditions. Far and near ultraviolet circular dichroism spectra showed that only minor changes in the secondary structure of fibronectin take place on increasing the glycerol content of the solvent up to 34% (w/v). Our results complement previously available information on the solution structure of fibronectin and on its transition from the native compact conformation to a more expanded form on increasing ionic strength or glycerol content. In either situation, fibronectin seems to retain a basic structural core, in which the N-terminal, the central and the C-terminal regions of the two subunits strongly interact with each other. A major role of hydrophobic forces, in stabilizing the fibronectin conformations under these conditions, is therefore postulated. The transition to the extended forms seen in many electron micrographs can instead be explained by disruption of the proposed structural core upon adsorption to surfaces. PMID- 8464069 TI - What is the natural boundary of a protein in solution? AB - At what distance do proteins in solution interact? Molecular simulation of water around two helices is used to address this question. Calculations are done with two ideal, parallel, polyalanine alpha-helices separated by 9 A, 11 A, 13 A, and 15 A. The second peak in the oxygen density (or loosely the second shell of water molecules) is used to define a hydration surface around the protein, which separates bulk solvent from water molecules strongly influenced by the protein. The hydration surface is contrasted with the Richards-Connolly molecular surface. It indicates that the helices are not completely separate until 15 A, while the molecular surface shows complete separation at 13 A. Suggesting shape-dependent aspects of hydration, the hydration surface only loosely follows the van der Waals outline of the protein surface. In particular, at the 9 A separation, the van der Waals envelopes of the helices make contact; two narrow crevices are formed on either side of the contact; and the water within the crevices is strongly localized in arrangements bridging the helices. A comparison of these 'normal' water simulations with a simulation of a simple, uncharged solvent highlights the importance of hydrogen bonding in structuring liquid water and further contrasts the molecular surface and the hydration surface. PMID- 8464070 TI - Determination of the rate constants k1 and k2 of the Linderstrom-Lang model for protein amide hydrogen exchange. A study of the individual amides in hen egg white lysozyme. AB - The pH dependence of the amide/solvent hydrogen exchange of individual amide groups in hen egg-white lysozyme has been studied by nuclear magnetic resonance spectroscopy. Lysozyme has been used here as a model for a globular protein to re examine the hypothesis for the amide/solvent hydrogen exchange reaction proposed by K. Linderstrom-Lang and described in detail by Hvidt and Nielsen. The work has been focused on the most slowly exchanging amide at the temperature of 21 degrees C and in the pH range between 4 and 8. Exchange rates have been measured for 64 of the 126 amide protons and the pH dependence has been determined for 52 of these. The amides examined represent a sample that includes all the types of secondary structure and they are placed in the globular structure in a range of 3.2 A to 8.5 A from the closest water molecule on the surface. The measured exchange rates at pH 6 have been compared to these structural parameters and the results suggest that the rate constants are determined partly by the distance to the surface and partly by the type of secondary structure the amide is engaged in. Near the surface and in the very interior the distance to the surface seems to be rate-determining. Between the extremes the type of secondary structure is rate determining. The pH dependent exchange of the examined amides was shown to be in agreement with the Linderstrom-Lang model. For each of the amides examined the rate constants for the opening and the closing reaction in the first reaction step of the Linderstrom-Lang model has been calculated and compared to structural parameters. PMID- 8464071 TI - Crystals of beta-xylanase from Aspergillus oryzae. AB - An endo-xylanase was isolated from the culture of fungus Aspergillus oryzae variant D5. The purified enzyme had a molecular weight of 24,000 and the isoelectric point of 3.6. Xylanase crystals were obtained from a polyethylene glycol 6000 solution by the hanging-drop method. Seeding was used for the enlargement of the crystal size. Crystals belong to the monoclinic space group P2(1) with cell dimensions a = 54.9 A, b = 74.5 A, c = 50.8 A, and beta = 108.7 degrees. Crystals diffract beyond 2.5 A resolution. PMID- 8464072 TI - Crystallization and preliminary X-ray analysis of a thermophillic Bacillus xylanase. AB - A xylanase of M(r) 20,700 from the hyperproductive mutant D3 of the thermophillic Bacillus, strain XE has been purified and crystallized from 2-methyl-2,4 pentanediol. The unit cell is triclinic with a = 48.5 A, b = 51.5 A, c = 72.6 A, alpha = 90.4 degrees, beta = 95.4 degrees, gamma = 92.3 degrees (all +/- 0.2). There are four molecules in the asymmetric unit related by 222 symmetry. These crystals diffract to at least 2.5 A using X-rays from a rotating anode generator. PMID- 8464073 TI - Crystallization and preliminary crystallographic analysis of a tetrameric isolectin from Vicia villosa, specific for the Tn antigen. AB - Isolectin B4 isolated from Vicia villosa seeds is specific for the Tn antigen, a carcinoma-associated molecular marker. Crystals of the isolectin grown in the presence of carbohydrate are tetragonal, space group P4(1) (or P4(3), with a = 91.3 A, c = 151.7 A and one tetramer in the asymmetric unit. The crystals diffract X-rays to 2.8 A resolution and are suitable for high-resolution structural analysis. PMID- 8464074 TI - Crystallographic characterization of tetanus toxin fragment C. AB - The C-terminal fragment from tetanus toxin has been crystallized. The 50 kDa protein forms prismatic crystals with an orthorhombic unit cell of dimensions a = 64.03 A, b = 76.31 A and c = 135.3 A. The space group is P2(1)2(1)2(1). Assuming one molecule per asymmetric unit, the solvent occupies 63% of the unit cell. PMID- 8464075 TI - Crystallization of the maltodextrin-binding protein for active transport and chemotaxis in several different liganded and mutant forms. AB - We have crystallized the maltodextrin-binding protein complexed with two cyclic maltodextrins, and with no ligand at all. We have also grown crystals of two complexes of a mutant of maltodextrin-binding protein whose transport specificity has been altered. Studies of these crystals should provide considerable information about protein-oligosaccharide interactions, the effects of these interactions on oligosaccharide conformation, and particularly about the function of the periplasmic receptors in transport and chemotaxis. PMID- 8464076 TI - Preliminary crystallographic data for Pneumocystis carinii dihydrofolate reductase. AB - Dihydrofolate reductase from Pneumocystis carinii has been crystallized in a form suitable for high resolution X-ray diffraction studies. Recombinant enzyme that had been refolded following solubilization in guanidinium hydrochloride was crystallized as both a ternary complex with the cofactor NADPH and the inhibitor trimethoprim as well as a binary complex with NADPH. The two types of complex crystallized isomorphously from polyethylene glycol using sitting-drop vapour diffusion. The crystals were of space group P2(1) with unit cell parameters, a = 69.9 A, b = 43.6 A, c = 37.6 A, beta = 117.7 degrees, with one molecule per asymmetric unit. The crystals diffracted to 1.8 A resolution. PMID- 8464077 TI - Preliminary X-ray study of naproxen esterase from Bacillus subtilis. AB - Single crystals of naproxen esterase from Bacillus subtilis have been obtained from PEG6000 solutions at pH 8.0 by liquid-liquid diffusion while applying a temperature gradient from 4 degrees C to room temperature over a period of four weeks. The crystals belong to the trigonal space group P3(1)21 or P3(2)21 with a = b = 47.59 A and c = 212.91 A. The asymmetric part of the unit cell contains one protein molecule with M(r) = 33,771. The crystals diffract to at least 3.0 A resolution and are suitable for an X-ray structure analysis. PMID- 8464078 TI - Prokaryotic members of a new family of putative helicases with similarity to transcription activator SNF2. AB - Cloning and sequence analysis of a new open reading frame from Bacillus cereus reveals the relationship to a recently identified family of putative eukaryotic transcription activators similar to the yeast SNF2 gene product. As a result of comparative analysis of sequence features conserved in all members of this family, a gene from a chilo iridescent virus, as well as a putative helicase from Escherichia coli (hepA), can also be grouped into this family. The unexpected presence of prokaryotic and viral sequences in the previously purely eukaryotic SNF2 family suggests a defined subgroup of DNA helicases present in all species, with specific function in transcription activation. PMID- 8464079 TI - Sweet-tasting protein monellin is related to the cystatin family of thiol proteinase inhibitors. AB - The structure of the intensely sweet protein monellin, isolated from an African berry, and the structures of two thiol proteinase inhibitors, cystatin and stefin B, are found to be very similar. An alignment of sequences of monellin and the inhibitors, deduced from the structural comparisons, has been extended to include other members of the cystatin superfamily. There is a significant homology (up to 23% identical residues) with oryzacystatins, the only well defined plant cystatins. These results clearly indicate that monellin is a close relative of cystatins. Monellin and cystatins do not have the same sequence in the regions homologous to the cystatin active site. It is suggested here, however, that this region in monellin may be essential for a function in situ, because one of the loops comprising this part of the structure is found to be cleaved. PMID- 8464080 TI - Infected infrarenal aortic aneurysms: when is in situ reconstruction safe? AB - Twenty-five infected infrarenal aortic aneurysms operated on between 1968 and 1989 were reviewed. They were classified into post-embolic (mycotic) aneurysms (group I), infective aortitis (group II), and infected atherosclerotic aneurysms (group III). Aortoduodenal fistulas were found in eight patients and aortocaval in two. Five patients were operated on in a state of shock, and 12 had preoperative positive blood cultures. Surgical procedures included in situ reconstruction of the aorta (n = 21) and extra-anatomic bypass associated with aneurysmal resection (n = 4). In 19 patients, prostheses were covered with omental flaps, and antibiotics were continued for more than 6 weeks in all patients. In patients who underwent in situ reconstruction, three deaths were related to the initial surgery. All surviving patients were regularly followed up, and none showed any sign of late septic recurrence. In patients who underwent extra-anatomic bypass, two died in the postoperative period, one underwent reoperation 2 years after the initial surgery, and the last patient is doing well. Positive postoperative blood cultures (n = 4) revealed persistent sepsis: two cholecystitis, one spondylitis, and one aortic infection. An exhaustive review of the literature was performed; clinical, bacteriologic, and operative features and results were analyzed; prognostic factors were evaluated; and a practical therapeutic approach was suggested. The importance of preoperative diagnosis, complete resection, debridement of infected tissues, omental flap coverage, and long-term antibiotic therapy with regular computerized tomographic scanning follow-up is stressed. PMID- 8464081 TI - Hemodynamics of a side-to-end proximal arterial anastomosis model. AB - PURPOSE: The purpose of this article was to analyze the fluid mechanical effects of a side-to-end proximal anastomosis and to compare the results with those from our earlier study on the end-to-side distal anastomosis. METHODS: The photochromic tracer technique was used to determine the instantaneous wall shear stress and to visualize the overall flow field under pulsatile flow conditions. The flow consisted of a sinusoid plus a steady component with mean and modulation Reynolds numbers of 355 and 565, respectively, and a Womersley number of 7.9. RESULTS: At the toe and heel of the junction, very high and positive wall shear stresses were seen together with substantial nonperiodic fluctuations. The peak wall shear stress was about four times higher at the toe and about seven times higher at the heel than the maximum values observed at about four tube diameters upstream from the junction. On the bed of the host vessel, nonperiodic fluctuations were also observed, but the shear stresses were mainly negative with magnitudes comparable to those seen upstream. With leakages of 11% and 28% of the mean flow through the blocked end of the host vessel, the shear stress pattern seemed to be significantly affected only at the toe for the higher leakage. Further, when the mean Reynolds number was reduced to 320, the magnitudes of the variations in the wall shear stress were reduced proportionately, except at the heel, where the reduction was much larger than expected. CONCLUSIONS: It appears that the preferential development of intimal hyperplasia at the distal end-to side anastomosis may be promoted by low wall shear stress at the toe and heel, and probably by high shear stresses or shear stress gradients on the bed. PMID- 8464082 TI - Three-dimensional display of calculated velocity profiles for physiological flow waveforms. AB - PURPOSE: To improve the understanding of the nature of pulsatile flow, three dimensional idealized velocity profiles corresponding to measured physiological mean flow velocity waveforms were displayed at selected instants throughout the flow cycle. METHODS: The Fourier harmonics for each waveform were determined, and their corresponding velocity profiles at each instant of time were calculated with the Womersley equations. Velocity profiles were calculated by summing the contributions from each harmonic. RESULTS: Calculated profiles were displayed in a three-dimensional perspective for both normal carotid and femoral arteries and for simple sinusoidal flow with a superimposed steady component. CONCLUSION: The potential value of such displays is discussed in terms of gaining an improved understanding of the nature of pulsatile flow and clarifying the interpretation of Doppler ultrasound recordings. PMID- 8464083 TI - Postischemic hyperglycemia worsens neurologic outcome after spinal cord ischemia. AB - PURPOSE: The neurologic effect of induced hyperglycemia in the postischemic period was investigated with a rat aortic occlusion model. METHODS: Sprague Dawley rats weighing 200 to 350 gm were anesthetized, intubated, and ventilated with 1% to 1.5% halothane. Temperature was continuously monitored and maintained at 37 degrees +/- 0.5 degrees C. The chest was opened, the thymus excised, and the aortic arch exposed. Snares were placed around the aorta distal to the left subclavian artery and the right and left subclavian arteries. The three vessels thus isolated were occluded for 8 minutes. With snare release and withdrawal, the rats received an intraperitoneal injection of 5% dextrose in water (2 gm/kg) or an equivalent volume of 0.9% saline solution. In a second group of rats the administration of glucose or saline solution was delayed until 30 minutes after snare release. Blood samples for blood glucose determination were obtained before operation, before occlusion, immediately after occlusion, and 15, 30, 45, 60, and 240 minutes after occlusion. A neurologic deficit score was assigned at 1, 4, 18, and 24 hours after occlusion to quantify hindlimb neurologic deficit based on 15 point scale (0 = normal, 15 = severe deficit). Sham-operated rats received the same operation and injection, but the snares were only manipulated and not made occlusive. RESULTS: The rats that were administered glucose immediately after snare release showed a statistically significant exacerbation of lower extremity neurologic deficit at 24 hours after occlusion (p < or = 0.05, Mann-Whitney U test). The sham-operated rats were normal (0 score) at 24 hours. Significant elevation of blood glucose (321 +/- 33 mg/dl) was seen in the glucose-injected rats at 15 minutes and continued for up to 4 hours after occlusion (p = 0.040 and 0.014, respectively; Student's t test). CONCLUSION: Postischemic hyperglycemia immediately after a standard spinal cord ischemic stress worsens neurologic outcome. PMID- 8464084 TI - Leukocytes: their role in the etiopathogenesis of skin damage in venous disease. AB - The role of leukocytes in tissue damage in the liposclerotic skin of venous disease has been investigated. Twenty-eight skin biopsy specimens were obtained from 23 patients with varicose veins of the lower limb, with a spectrum of skin injury ranging from normal to severe liposclerosis. In no patient was a venous ulcer present. Immunohistochemistry was used to determine the cell types present and provide an indication of their activity. The predominant infiltrating cell types present were T lymphocytes and macrophages. B cells and neutrophils were rarely seen. As described previously, the capillaries were greatly increased in number in the papillary dermis and exhibited grossly increased expression of factor VIII-related antigen and major histocompatibility complex class II. Surprisingly, expression of adhesion molecules endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule were not elevated, but intercellular adhesion molecule-1 expression did increase in more severely diseased skin. Perivascular fibrin was seen occasionally, but there was no evidence of microvascular occlusion. Staining for the cytokine tumor necrosis factor-alpha was not increased in liposclerotic skin. Dermal staining for both interleukin (IL)-1 alpha and IL-1 beta was increased in severely liposclerotic skin, but this was not seen at an early stage. Epidermal staining for IL-1 alpha and IL-1 beta was not increased. All changes were confined to the subpapillary region of the skin. These findings demonstrate that accumulation of macrophages and T cells is an event associated with the development of liposclerotic skin changes that may lead to ulceration in venous disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464085 TI - How can the assessment of the hemodynamic significance of aortoiliac arterial stenosis by duplex scanning be improved? A comparative study with intraarterial pressure measurement. AB - PURPOSE: The current diagnostic criteria used to assess the severity of stenoses in the aortoiliac arteries by duplex scanning are mainly based on information related to changes in cross-sectional area and are flow independent. Consequently, duplex scanning fails to detect approximately one quarter of hemodynamically significant aortoiliac lesions compared with intraarterial pressure measurements. The aim of this study is to improve the assessment of the hemodynamic significance of aortoiliac lesions by duplex scanning. METHODS: A prospective study in 60 patients was performed in which duplex scanning at rest was compared with intraarterial pressure measurements before and after the administration of papaverine. A simplified Bernoulli equation was used to calculate pressure gradients across stenoses (delta PBern). Two flow-related parameters, the increase in peak systolic velocity (delta PSV) across the stenosis and the end-diastolic velocity at the site of the stenosis, were also measured and compared with intraarterial pressure measurements. RESULTS: delta PBern and delta PSV showed a sensitivity and specificity of 81% and 88%, respectively, for the detection of hemodynamically significant lesions at rest. However, delta PBern could often not give an accurate calculation of the pressure gradient. Receiver operator characteristic analysis showed that a cut-off level for delta PSV in the range of 1.4 to 1.5 m/s was best able to detect significant lesions at rest. The end-diastolic velocity parameter had a limited diagnostic value. CONCLUSION: Although useful in clinical decision making, delta PBern often could not give an accurate calculation of the pressure gradient. delta PSV is a simple and practical spectral analysis parameter to differentiate between significant and insignificant stenoses. This parameter also has the potential to detect hemodynamically less critical lesions if duplex scanning is performed under conditions of increased flow. Further evaluation is needed. PMID- 8464086 TI - Attenuation of renal reperfusion injury in rats by the 21-aminosteroid U74006F. AB - PURPOSE: The 21-aminosteroids represent a new class of compounds that serve as potent inhibitors of iron-dependent lipid peroxidation, the latter being an important component of ischemia-reperfusion tissue injury. It is hypothesized that reperfusion injury accompanies renal ischemia, and postischemic administration of one of these steroids, U74006F, will reduce renal damage in a rodent model, as assessed by renal function (plasma creatinine), histologic evidence of renal injury, and animal survival during a 72-hour interval. METHODS: Fifty-one rats subjected to 45 minutes of renal ischemia were treated on clamp release with 3 or 10 mg/kg U74006F intravenously (n = 5 and 19, respectively), an inactive vehicle (n = 23), or sham operation (n = 4). RESULTS: Both doses of U74006F improved morphologic outcome compared with vehicle-treated animals. Statistically significant improvement in renal function was observed with the 10 mg/kg dose of U74006F (p = 0.029, 0.014, and 0.065 at 24, 48, and 72 hours, respectively) but not with the 3 mg/kg dose. Only one (5.2%) of 19 rats receiving high-dose U74006F (10 mg/kg) died within 72 hours after ischemia, compared with five deaths (29.4%) in 17 rats receiving citrate vehicle alone (p = 0.060). All sham-operated animals survived 72 hours with normal morphology and plasma creatinine levels. CONCLUSION: These data suggest that iron-dependent lipid peroxidation is a component of reperfusion injury and indicate that U74006F may be useful in reducing this form of renal ischemic damage. PMID- 8464088 TI - Abdominal duplex ultrasound screening for occult aortic aneurysm during carotid arterial evaluation. AB - PURPOSE: The purpose of this study was to investigate the use of a modified abdominal ultrasound examination, which was performed at the time of routine diagnostic carotid artery duplex evaluation, to identify patients at risk for aortic aneurysms. METHODS: A prospective study was undertaken that consisted of a limited ultrasound examination of the abdominal aorta on patients referred to our facilities for duplex carotid evaluation. One hundred thirty-one patients were included in the study; 52% were men and 48% were women, who ranged in age between 40 to 93 years. These patients were not known or suspected to have an abdominal aortic aneurysm. RESULTS: Eleven infrarenal aortic aneurysms (8.4%) were detected, four in patients with positive carotid studies (11%) and seven in those with negative studies (7%); size ranged from 3.0 to 7.5 cm. Categoric data analysis did not produce significance, but a stepwise regression and discriminant analysis model revealed a significant relationship between abnormal velocities and occlusive changes in the carotid arteries and the presence of aortic aneurysms. CONCLUSIONS: Hemodynamically significant carotid artery disease, as diagnosed by duplex examination, appears to be a definite marker for an increased incidence of abdominal aortic aneurysm when compared with the general population. When selective abdominal aortic ultrasonography is done in conjunction with the carotid study, the requirements of additional equipment and technologist time are modest, and the potential benefit to the patient may be significant. PMID- 8464087 TI - The cerebral hyperperfusion syndrome: diagnostic value of ocular pneumoplethysmography. AB - PURPOSE: There were two purposes to our study. The first was to characterize the ocular hyperperfusion associated with carotid endarterectomy. The second was to relate ocular hyperperfusion to the clinical presentation of cerebral hyperperfusion syndrome. METHODS: This was a retrospective chart review of 2331 patients who underwent carotid endarterectomy at our institution between June 1978 and May 1991. RESULTS: Twelve of these carotid endarterectomies were associated with ocular hyperperfusion on the side of operation. Clinical evidence of cerebral hyperperfusion syndrome was observed in five of these 12 procedures. In these five patients there were two associated fatal intracerebral hemorrhages and one permanent coma. In the latter three patients the contralateral internal carotid arteries were totally occluded. CONCLUSION: Ocular hyperperfusion, as documented with ocular pneumoplethysmography, is useful in alerting the physician to the potential for development of the cerebral hyperperfusion syndrome. PMID- 8464089 TI - Radiologic investigation of abdominal aortic aneurysm disease: comparison of three modalities in staging and the detection of inflammatory change. AB - PURPOSE: The purpose of this study was to compare the ability of ultrasonography (US), contrast-enhanced computed tomography (CT), and magnetic resonance imaging (MRI) to display the anatomy of abdominal aortic aneurysms and to detect the presence of inflammatory change. METHODS: We prospectively studied 79 patients with abdominal aortic aneurysms (64 noninflammatory aneurysms [NIAAs] and 15 inflammatory aneurysms [IAAs]) with US, CT, and MRI. RESULTS: Ultrasonography failed to diagnose the level of the aneurysm neck in three IAAs and 18 NIAAs. It failed to differentiate NIAAs from IAAs and to visualize the origins of the renal arteries in all cases. With CT the level of the aneurysm neck was incorrectly stated as lying above the level of the renal arteries in two cases of IAA and four cases of NIAA, and the renal artery origins were seen in only 10 of 77 patients. Inflammatory change was diagnosed correctly in seven of 15 patients, whereas six NIAAs were falsely diagnosed as inflammatory. MRI successfully diagnosed neck level and inflammatory change in all cases. Of two failures to visualize the renal artery origins, only one was caused by radiologic factors. In addition, characteristic radiologic features were seen in MRI images of IAAs, and these will be described both in vivo and in vitro. CONCLUSIONS: Our results suggest that MRI is superior to other methods in identifying the anatomy of aneurysms and the presence of inflammatory change. PMID- 8464090 TI - Human vascular endothelial cell attachment and growth inhibition by type V collagen. AB - PURPOSE: Human vascular prostheses develop a pseudointima that after time is devoid of a complete endothelial lining. The composition of this pseudointima consists of both cellular and noncellular components such as coagulation proteins and extracellular matrix proteins. Of these extracellular molecules, type V collagen has been reported to be localized to surfaces of vascular prostheses. We have hypothesized that type V collagen may be involved in the mechanisms of inhibition of endothelialization on vascular prostheses. In this study, interactions of human protein and cells with clinically used material and reference surfaces were analyzed in vitro. METHODS AND RESULTS: Human collagen types IV and V or human fibronectin was coated on disks punched from expanded polytetrafluoroethylene, bacteriologic polystyrene, and tissue culture-treated polystyrene. Fibronectin adsorbed equally to these surfaces, but differential adsorption of type V collagen occurred. The attachment and growth of human saphenous vein and umbilical vein endothelial cells and of human skin fibroblasts were also evaluated on protein-coated or uncoated surfaces. Type IV collagen and fibronectin promoted the attachment of these cells, but type V collagen reduced cellular adhesion. Growth of endothelial cells was significantly inhibited on surfaces coated with type V collagen even when additional growth substances such as serum, retinal-derived growth factor, and heparin were present in the medium. Human adult dermal fibroblast adhesion and cell growth were not affected by coating the surfaces with type V collagen. CONCLUSIONS: The components of the extracellular matrix of the pseudointima may directly influence endothelial cells by inhibiting cell proliferation, migration from within the graft or from anastomoses, or both. Type V collagen, a matrix protein found at luminal surfaces of vascular prostheses, may be one protein responsible for control of endothelial responses. PMID- 8464091 TI - Measurement of the ultrasonic intima-media complex thickness in normal subjects. AB - PURPOSE: The evolution of atherosclerosis can be studied before development of symptomatic plaque by evaluating morphologic changes of the intima-media (I-M) complex, seen on high-resolution ultrasonography of the arterial wall. These qualitative changes require large alterations in vessel wall appearance to recognize progression of atherosclerosis. It has been suggested that measurement of the thickness of the I-M complex may be a quantitative and more sensitive method of assessing these early atherosclerotic changes. METHODS: High-resolution ultrasonography has been used to measure the thickness of the I-M complex in 140 symptom-free subjects. RESULTS: The mean thickness of the I-M complex of the common carotid arteries was linearly related to the age (r = 0.77; p < 0.001), pack-years of smoking (r = 0.39; p < 0.05), the systolic blood pressure (r = 0.51, p < 0.01), and to the arterial ultrasound score (r = 0.85). The arterial ultrasound score has previously been shown to correlate with the presence of asymptomatic myocardial ischemia and with the development of cardiovascular symptoms. The mean thickness of the I-M complex in subjects without plaque (in the common carotid or common femoral artery bifurcations) was significantly thinner than in subjects with plaque (p < 0.001). CONCLUSION: The thickness of the I-M complex of the common carotid arteries is a measure of the risk for the development of cardiovascular symptoms in symptom-free individuals. PMID- 8464092 TI - Effects of donor characteristics and platelet in vitro time and temperature on platelet aggregometry. AB - PURPOSE: This study was undertaken to determine whether platelet donor characteristics and the duration and temperature of platelet storage affect platelet aggregation. METHODS: Half of each platelet-rich plasma sample, obtained from 42 healthy volunteers, was maintained at 37 degrees C and the other half at 25 degrees C. Aggregation was stimulated with adenosine diphosphate (ADP), epinephrine, or collagen 1, 2, 4, and 6 hours after platelet donation. The lag time, slope of the aggregation curve, and percent peak aggregation were determined for each aggregation test. RESULTS: Age, sex, time of donation, smoking status, estrogen replacement, and menstruation did not significantly influence platelet aggregation. Storage time and temperature had a major influence on platelet reactivity, with the reactivity decreasing with prolonged storage and higher storage temperatures. Peak ADP-induced aggregation for platelets stored at 37 degrees C was significantly less (p < 0.0002) than the values obtained for ADP aggregation at 25 degrees C. Collagen-stimulated peak aggregation of platelets maintained at 37 degrees C for 4 and 6 hours was also significantly less than the corresponding values at 25 degrees C. Epinephrine stimulated aggregation produced similar results, with peak platelet aggregation decreasing with time (50.3% +/- 2.9% at 6 hours compared with 38.5% +/- 3.7% at 2 hours at 25 degrees C) and high storage temperatures (there was less aggregation by platelets stored at 37 degrees C at each time period studied). CONCLUSIONS: It is recommended that platelet-rich plasma for platelet aggregation testing be maintained at room temperature and be used between 2 and 4 hours after platelet donation. PMID- 8464093 TI - Intestinal permeability is increased after major vascular surgery. AB - PURPOSE: In experimental animals increased intestinal permeability has been demonstrated after ischemia and reperfusion injury. In this study we determined intestinal permeability in patients after elective or emergency aortic aneurysm repair; the latter patients were in severe shock on hospital admission. METHODS: A dual sugar absorption test, with lactulose and mannitol as markers, was used to measure intestinal permeability on the second day between 24 and 30 hours after hospital admission. RESULTS: The lactulose/mannitol excretion ration was 0.012 +/ 0.005 in seven healthy control subjects, 0.118 +/- 0.116 in seven patients having elective operation, and 0.098 +/- 0.093 in eight patients having emergency operation, indicating a significant increase of intestinal permeability in both patient groups (p < 0.01). No significant difference was found in intestinal permeability between patients of the elective and emergency groups. CONCLUSIONS: A significant increase in intestinal permeability commonly occurs in patients after elective and emergency major vascular surgery. It is suggested that this is mainly due to reperfusion injury rather than the ischemic period of the intestine itself. PMID- 8464094 TI - Detection of celiac axis and superior mesenteric artery occlusive disease with use of abdominal duplex scanning. AB - PURPOSE: Detection of mesenteric arterial insufficiency is clinically difficult, and diagnosis frequently requires arteriography. Advances in duplex scanning make this an ideal technique to noninvasively screen patients for chronic mesenteric arterial occlusive disease. However, the accuracy of mesenteric duplex scanning compared with arteriography remains unclear. This study will clearly define the accuracy of abdominal duplex scanning for detection of mesenteric arterial insufficiency. METHODS: The mesenteric duplex scans of 38 patients obtained over a 4-year period were reviewed and compared with lateral aortograms to clarify this issue. Optimal peak systolic frequency (PSF) for predicting less than 50% or 50% or greater stenoses of the superior mesenteric artery (SMA) and celiac axis (CA) were determined from receiver-operating characteristic curves. RESULTS: In the SMA a PSF of 4.5 kHz was 96% sensitive (24/25), 92% specific (12/13), and 95% accurate (36/38) at predicting stenoses less than 50% or 50% or greater. For arteries with stenoses 50% to 99%, regression analysis demonstrated excellent linear correlation between percent stenosis and PSF (r = 0.89). In the CA a PSF of 4.0 kHz had a sensitivity of 100% (30/30), a specificity of 88% (7/8), and an accuracy of 97% (37/38). Again, for arteries with stenoses 50% to 99%, an excellent linear correlation existed between PSF and percent stenosis (r = 0.86). All total arterial occlusions (14) were correctly identified. In all, mesenteric arterial duplex scanning was 96% accurate for predicting SMA and CA stenoses/occlusions. CONCLUSIONS: Abdominal duplex scanning is a noninvasive technique that accurately detects total occlusions and objectively quantitates SMA and CA arterial stenoses. PMID- 8464095 TI - Evaluation and performance standards for arterial prostheses. PMID- 8464096 TI - Spontaneous rupture of the iliac vein. AB - A spontaneous rupture of the left iliac vein is described. A 2 cm tear on the anterior surface of the left iliac vein was discovered at emergency laparotomy on a patient who was suspected of having a huge intraabdominal hemorrhage. Prodromal symptoms, cause, and treatment are discussed. The nine previously reported cases are reviewed. This case represents the seventh successful repair of an idiopathic rupture of an iliac vein. PMID- 8464097 TI - Polytetrafluoroethylene aorta-vena cava graft for hemodialysis: report of a case. AB - In children with chronic renal failure, vascular access for hemodialysis is difficult because of the small size of the vessels and the requirement for substantial blood flow through the fistula or graft. As the child grows older, the ease of constructing a satisfactory access usually increases as the vessels increase in size. Unfortunately, this increased ease is often offset by the paucity of suitable access sites because the larger peripheral sites have already been used with only transient success. We report a child with chronic renal failure since 1 month of age with no peripheral sites available because of prior failed procedures who underwent placement of polytetrafluoroethylene limbs to the aorta and vena cava at the age of 6 years. He has continued on hemodialysis for the past 4 1/2 years with this technique of vascular access. PMID- 8464098 TI - True and false aneurysms in Behcet's disease: case report with ultrastructural observations. AB - One of the most important aspects of Behcet's disease is aneurysmal arteriopathy. The major problem of this complication is its tendency to develop recurrent false aneurysms at anastomotic and traumatic sites, such as angiographic punctures. We present a clinical case in which five aneurysms, some true, some false, were operated on during a period of 6 years, with the aid of ultrastructural observations of the wall of a true and a false aneurysm. One of the true aneurysms, localized in the aorta, was treated by direct aneurysmorrhaphy, and the 6-year follow-up demonstrated the absence of recurrences. Based on both this experience and the data in the literature, we suggest that the most appropriate surgical approach would, when possible, be direct aneurysmorrhaphy. PMID- 8464099 TI - In situ replacement of infected vascular prostheses with rifampin-soaked vascular grafts: early results. AB - Based on the excellent results of experimental studies with antibiotic-bonded vascular prostheses for prevention of graft infection, gelatin-sealed grafts soaked with rifampin were implanted in situ in five patients with vascular infection. All patients were at risk for limb loss or death and could not be treated by standard techniques such as graft excision and extra-anatomic bypass. In one patient an infected aortic stump aneurysm with involvement of both renal and visceral arteries was found. He was treated by implantation of a bifurcation rifampin-soaked graft between the subdiaphragmal aorta and both renal arteries and reimplantation of celiac and superior mesenteric artery into the graft. In four patients with in-flow or runoff problems on angiography, an antibiotic soaked graft was used for replacement of a partially or totally infected graft. Cultures were positive for Staphylococcus aureus in three and coagulase-negative staphylococci in two patients. Wound healing was uncomplicated; there was no need for amputation. After a follow-up of at least 6 months, all grafts were patent without any evidence of reinfection on computed tomographic scan. We conclude that infected vascular prostheses can be replaced in situ by rifampin-soaked grafts in patients at high risk for death or major amputation. PMID- 8464100 TI - Recreational weight lifting and aortic dissection: case report. AB - Although there have been previous cases of ascending (type I) aortic dissection recognized in young weight lifters, this is the first reported instance of a descending (type III) dissection in such an individual. Successful treatment included aortic fenestration and an aortoiliac bypass. A new entity of aortic dissection in young weight lifters may be emerging. PMID- 8464101 TI - Nonanastomotic pseudoaneurysm of expanded polytetrafluoroethylene axillofemoral bypass graft. AB - A case of nonanastomotic pseudoaneurysm of a unilateral axillofemoral bypass graft is reported. The graft material used in this particular instance was an 8 mm, reinforced, thin-walled, fluorinated ethylene-propylene-ringed, expanded polytetrafluoroethylene (ePTFE). The pseudoaneurysm occurred 1 year after insertion of the graft and was not associated with any direct trauma. It manifested with a painful tender mass at the top of the body of the axillofemoral bypass graft at the level of the nipple line. There were no symptoms of localized or diffuse sepsis. Immediate surgical exploration confirmed the diagnosis of a pseudoaneurysm of the ePTFE graft. Successful repair of the disrupted segment was accomplished by use of an interposition, nonringed, reinforced, thin-walled, 8 mm ePTFE graft. To our knowledge this is the first case of a nonanastomotic pseudoaneurysm of a ringed, ePTFE, axillofemoral bypass graft not associated with direct trauma. PMID- 8464102 TI - Chronic traumatic thoracic aneurysm: report of two cases with the question of timing for surgical intervention. AB - We report on two symptom-free patients with chronic thoracic aneurysms related to prior trauma and address the timing for surgical intervention. In addition, we reviewed our institutional experience with similar cases for the period 1970 to 1990. Although natural history data remain incomplete, we propose that in the setting of improved imaging modalities, it may be reasonable to manage this group of patients nonoperatively and intervene surgically only when symptoms develop or there is radiologic evidence of aneurysm change. PMID- 8464103 TI - Inferior pancreaticoduodenal artery aneurysm: report of a case and review of the literature. AB - Inferior pancreaticoduodenal artery aneurysms are rare, with only 34 cases reported in the literature. Most cases reported have begun with variations of abdominal or epigastric pain. We report a unique case of aneurysm of the inferior pancreaticoduodenal artery that began with intestinal angina and weight loss. PMID- 8464104 TI - Bilateral carotid artery thrombosis in a young man. AB - Carotid artery thrombosis in young patients without evidence of premature atherosclerosis prompts investigation of unusual forms of carotid disease in addition to a workup for cardiac and arch vessel sources for emboli. Noninvasive imaging and conventional angiographic techniques play an important part in the diagnostic evaluation looking for potential vascular sources. Physicians should also be aware that, in addition, hypercoagulable conditions may predispose to carotid thrombosis. One such patient is presented with bilateral carotid thrombosis and stroke. The management of the problem is reviewed, as well as the investigation of potential hypercoagulable conditions, with a primary focus on qualitative and quantitative platelet abnormalities. PMID- 8464105 TI - Transcatheter embolization of an aortocaval fistula caused by residual renal artery stump from previous nephrectomy: a case report. AB - An arteriovenous fistula between the renal artery and vein is a rare complication of nephrectomy. We report the first case of direct inferior vena cava to renal artery fistula after nephrectomy. In addition, this was the first use of the Amplatz "spider," a vascular obstructing device used to trap coils during transcatheter embolization of a high-flow fistula. The patient's fistula was embolized successfully, with immediate improvement of symptoms and without pulmonary embolization. PMID- 8464106 TI - Carotid endarterectomy for asymptomatic stenosis: benefits confirmed by randomized trial. PMID- 8464107 TI - Lumbar radiofrequency sympatholysis. AB - PURPOSE: The purpose of this article is to present a modified technique for lumbar radiofrequency sympatholysis and to compare the results with chemical sympatholysis. METHODS: Eight patients underwent the percutaneous procedure on an outpatient basis. Sympatholysis was produced with a radiofrequency lesion generator according to distinct anatomic criteria. RESULTS: Six of eight patients met previously used criteria for sympatholysis 8 weeks after the procedure. Postsympatholytic neuralgia occurred transiently in 50% of patients. CONCLUSIONS: The technique produces sympatholysis comparable to that produced by phenol 6%, while it theoretically avoids the risk of neurologic deficits associated with chemical agents. The technique may be useful in patients for whom surgical sympathectomy is undesirable. PMID- 8464108 TI - Polytetrafluoroethylene interposition grafts for carotid reconstruction. PMID- 8464109 TI - Mitochondrial DNA studies help identify lost victims of human rights abuses. PMID- 8464111 TI - Physicians tell Washington 'you want our help'. PMID- 8464110 TI - Gene hunters nab the Huntington's defect; now tests can suggest not only if but when. PMID- 8464112 TI - From the Office of Technology Assessment. PMID- 8464113 TI - From the Centers for Disease Control and Prevention. Sliding-associated injuries in college and professional baseball--1990-1991. PMID- 8464114 TI - From the Centers for Disease Control and Prevention. Cigarette smoking among adults--United States, 1991. PMID- 8464116 TI - A piece of my mind. The captain. PMID- 8464115 TI - From the Centers for Disease Control and Prevention. Prenatal care, pregnancies complicated by diabetes. PMID- 8464117 TI - Transdermal nicotine: clarifications, side effects, and funding. PMID- 8464118 TI - Transdermal nicotine: clarifications, side effects, and funding. PMID- 8464119 TI - Transdermal nicotine: clarifications, side effects, and funding. PMID- 8464120 TI - Functional status in children with asthma. PMID- 8464121 TI - Social catastrophe: orphaned by AIDS. PMID- 8464122 TI - Social catastrophe: orphaned by AIDS. PMID- 8464123 TI - Can states take the lead in health care reform? PMID- 8464124 TI - Improving access to primary care. PMID- 8464125 TI - Improving access to primary care. PMID- 8464126 TI - Accuracy of the death certificate in a population-based study of asthmatic patients. AB - OBJECTIVE: To quantify the reliability of death certificate data concerning asthma. DESIGN: The complete medical records of decedents were reviewed by a physician certified in allergy and pulmonology who determined the cause of death without having access to the original death certificate. Disagreements between the death certificate and the reviewer were adjudicated by an expert panel. SETTING: The community of Rochester, Minn. PATIENTS: The mortality cohort included 339 deaths from a larger cohort of 5241 Rochester residents who received medical treatment for asthma between 1964 and 1983. MAIN OUTCOME MEASURES: Kappa coefficients were used to measure agreement beyond that expected by chance between the reviewer and the death certificate. The sensitivity and specificity of the death certificate diagnosis of asthma were calculated against the standard of the reviewer/panel diagnosis. RESULTS: Death certificates reported asthma as an immediate or underlying cause of death in 22 instances (6%), whereas the reviewer/panel identified asthma in 53 cases (16%). In four cases, the death certificate listed asthma and the panel identified another cause of death. The death certificate had a sensitivity of 42% and a specificity of 99% compared with the reviewer/panel. Agreement between death certificates and the reviewer was not influenced by whether an autopsy was performed. CONCLUSIONS: Death certificate diagnosis of asthma as an underlying cause of death had a low sensitivity but a high specificity. Increases in mortality due to asthma are not likely caused by false-positive diagnoses of asthma as an underlying cause of death. Asthma mortality rates, determined from death certificate data, may indeed underestimate actual asthma-related mortality. PMID- 8464127 TI - Relationship between parental trinucleotide GCT repeat length and severity of myotonic dystrophy in offspring. AB - OBJECTIVE: To assess the relationship between the GCT repeat number in the myotonic dystrophy gene and the clinical phenotype and examine its predictive utility in prenatal testing. DESIGN: DNA from patients was examined for the length of the myotonic dystrophy GCT repeat region, using both Southern blot analysis and polymerase chain reaction. The results were compared with the clinical onset of disease, as well as with pregnancy outcomes. SETTING: Patient samples were referred to the Kleberg DNA Diagnostic Laboratory at the Baylor College of Medicine for DNA analysis by geneticists and genetic counselors (84%), neurologists (10%), and obstetricians and other specialists (6%). Clinical features including onset of disease and family pedigrees were determined by the referring centers. PATIENTS: A total of 241 patient samples from 118 families referred from primarily genetic or neurological centers for genetic linkage analysis or mutation analysis for myotonic dystrophy. This included 44 families referred for prenatal diagnosis. MAIN OUTCOME MEASURES: A relationship between myotonic dystrophy disease onset and length of the GCT repeat allele, parental origin of the disease allele, and results of prenatal diagnosis predictions of disease status were measured. RESULTS: There is a relationship between increasing repeat length and earlier clinical onset of disease. Essentially all (> 99%) myotonic mutations causing myotonic dystrophy are accounted for by GCT repeat amplification. Congenital myotonic dystrophy occurs with as few as 730 GCT repeats but only with alleles of maternal origin. Maternal GCT repeats were found as low as 75 (asymptomatic) that were amplified to result in a child with congenital myotonic dystrophy. Application of DNA diagnosis to 32 pregnancies provided an accurate method for identification of at-risk fetuses and allele enlargement. CONCLUSIONS: The GCT repeat in myotonic dystrophy is highly mutable. The triplet repeat amplification is highly specific for mutations involving the myotonin protein kinase gene accounting for myotonic dystrophy. The quantitation of triplet repeats can be more sensitive than physical, ophthalmologic, and electromyography examinations since the mutation can be detected in patients without evidence of myotonic dystrophy clinical findings. The length of the triplet expansion is influenced by the sex of the transmitting parent and is related to the clinical onset of disease features. Prenatal measurement of the GCT triplet repeat has utility for families with myotonic dystrophy risk since mutant and normal repeats are distinguishable and the length of mutant repeat alleles is associated with clinical severity. Thus, GCT triplet measurement provides a highly accurate means of detecting the myotonic dystrophy mutation in patients and offers a new reproductive option for families at risk for myotonic dystrophy. PMID- 8464128 TI - Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. 1953. PMID- 8464129 TI - Genetical implications of the structure of deoxyribonucleic acid. 1953. PMID- 8464130 TI - Inherited breast and ovarian cancer. What are the risks? What are the choices? PMID- 8464131 TI - What the double helix (1953) has meant for basic biomedical science. A personal commentary. PMID- 8464132 TI - Molecular medicine. A spin-off from the helix. PMID- 8464133 TI - Celebrating 40 years of the double helix. From a theory of biology to the care of patients. PMID- 8464134 TI - Asthma deaths. A social or medical problem? PMID- 8464135 TI - Methadone maintenance. New research on a controversial treatment. PMID- 8464136 TI - Altered fates--counseling families with inherited breast cancer. PMID- 8464137 TI - Alternate coronary artery spasm with ST-segment "seesaw" phenomenon in variant angina. AB - Five patients with variant angina showed alternating ST-segment elevation and contralateral ST-segment depression between the precordial and inferior leads in electrocardiographic recordings made during sequential anginal attacks. This electrocardiographic "seesaw" phenomenon was observed during ergonovine-induced attacks in 3 cases and during spontaneous attacks in 1 case. Another patient showed ST-segment elevation in a spontaneous attack and in other leads during hyperventilation. In all cases, the first attack was accompanied by ST-segment elevation in the inferior leads. Coronary arteriography demonstrated that in all cases, coronary arterial spasm occurred during the attacks in both coronary arterial systems. Significant organic coronary arterial stenoses (> 50%) were found in both the left anterior descending branch and the right coronary artery in 2 patients. The remaining 3 patients showed no significant organic stenoses in any major coronary artery. However, pre-anginal coronary arteriography demonstrated that 13 of the 15 major coronary arteries, including all 9 of the major coronary arteries in the patients without significant stenoses, were already spastic. An exercise stress test performed in the morning induced attacks with chest pain and electrocardiographic ST-segment elevation in all 5 patients. The patients having an alternate ST-segment elevation in separate leads had vasospastic tendencies in both coronary arterial systems. PMID- 8464138 TI - Effect of reperfusion by direct percutaneous transluminal coronary angioplasty on ventricular late potentials in cases of total coronary occlusion at initial coronary arteriography. AB - The relationship between the time required for reperfusion and the incidence of late potentials was studied in 94 patients who survived a first acute myocardial infarction (AMI) and who showed total occlusion of the infarct-related artery at an initial coronary arteriography. Sixty-three patients who successfully underwent direct percutaneous transluminal coronary angioplasty (PTCA), and 31 who were treated conventionally (controls), underwent signal-averaged electrocardiography. Direct PTCA patients were classified into 5 groups according to the time required for reperfusion: < or = 4, 4-6, 6-8, 8-10, and > or = 10 h. The incidence of late potentials in these groups was 8%, 12%, 14%, 33%, and 43%, respectively, and 48% in the controls. Late potentials were recorded more frequently as the period until successful reperfusion increased: the incidence of late potentials was significantly lower in the < or = 4 and 4-6 h groups than in the controls (p < 0.005 and p < 0.05, respectively). Therefore, reperfusion achieved within 6 h reduced the incidence of late potentials in AMI patients and may be effective for preventing malignant ventricular arrhythmias. PMID- 8464139 TI - Prediction of exercise tolerance in the chronic phase of myocardial infarction by using ventilatory gas analysis. AB - To predict exercise tolerance in the chronic phase of myocardial infarction (MI), cardiopulmonary exercise testing was performed using a ramp treadmill protocol in 25 patients at 1 and 3 months after the onset of MI. Oxygen uptake, heart rate and O2 pulse were estimated at rest, during a warm-up period, and at the levels of anaerobic threshold (AT), respiratory compensation (RC) and peak exercise. Results were as follows: 1) AT and peak oxygen uptake at 3 months after the onset of MI were 14.1 +/- 2.8 and 21.8 +/- 5.2 ml/min/Kg, respectively. 2) The subjects were divided into 2 groups according to peak oxygen uptake at 3 months: one showing peak oxygen uptake > 22 ml/min/Kg and the other < 22 ml/min/Kg. The former group (n = 13) was referred to as the good tolerance group, and the latter group (n = 12) was referred to as the poor tolerance group. Oxygen uptake at AT, RC and peak exercise was lower in the poor tolerance group than in the good tolerance group (11.2 vs 14.7, 15.1 vs 20.4, 17.1 vs 23.4 ml/min/Kg, respectively). 3) The increases in oxygen uptake from AT to RC and from AT to peak exercise were less in the poor tolerance group than in the good tolerance group. 4) O2 pulse at rest, warm-up, AT, RC and peak exercise were also lower in the poor tolerance group.2+ tolerance in the chronic phase of MI. PMID- 8464140 TI - The prognostic significance of exercise-induced silent ST-segment depression in patients after myocardial infarction. AB - To evaluate the prognostic value of exercise-induced silent ST-segment depression, 157 patients who had suffered myocardial infarction underwent symptom limited exercise testing and coronary angiography. Patients were divided into 3 groups according to the presence or absence of ischemic ST-segment depression and angina during exercise testing. Group A patients had ST-segment depression without angina. Group B patients had both ST-segment depression and angina. Group C patients had neither ST-segment depression nor angina. All patients were followed without coronary artery bypass graft or percutaneous transluminal coronary angioplasty for an average of 36 months and the frequency of coronary events (cardiac death, recurrent myocardial infarction and unstable angina pectoris) was compared. Group A patients had less severe coronary artery disease, greater coronary reserve during exercise and exercised longer than group B. However, the prognosis of group A was similar to group B, and was worse than group C. Using the Cox proportional hazards model, ischemic ST-segment depression was the most useful index for predicting future coronary events among the baseline values, coronary angiographic and exercise testing variables. However, angina during exercise testing was not an independent predictor. Thus, post infarction patients showing exercise-induced ST-segment depression should be treated carefully regardless of the presence or absence of angina. PMID- 8464141 TI - Ventilatory anaerobic threshold before and after cardiac valve surgery. AB - The purpose of this study was to objectively assess exercise tolerance before and after cardiac valve surgery by using an objectively determined ventilatory anaerobic threshold (AT). Nine patients (mean age: 38.2 +/- 8.1 years) with predominantly mitral regurgitant lesions were studied by a symptomatic maximal treadmill exercise test which included a determination of AT. The mean lengths of time from preoperative exercise testing to cardiac surgery, and from surgery to postoperative exercise testing were 5.9 +/- 4.0 and 12.1 +/- 8.3 months, respectively. The determination of AT on data plots was performed after blinding to patient identification and pre- vs postoperative status. After surgery, the clinical symptoms and NYHA class improved significantly with a decrease in the cardio-thoracic ratio and echocardiographic diastolic dimensions. The mean peak VO2 (ml/kg/min) increased significantly from 20.2 +/- 7.1 to 29.7 +/- 7.9 (p < 0.01). Together with these changes, AT (ml/kg/min in VO2) increased from a mean of 14.8 +/- 4.8 to 22.8 +/- 5.5 (p < 0.01). In conclusion, symptomatic improvement and an increase in peak oxygen uptake after cardiac valve surgery were accompanied by a significant increase in the objectively determined AT. AT determined in a blind manner provides an objective means of evaluating exercise tolerance when a double-blind intervention cannot be performed. PMID- 8464142 TI - Nonpharmacologic treatment of common atrial flutter guided by transient entrainment. AB - We attempted nonpharmacologic treatment for common atrial flutter in 7 patients, with direct current catheter ablation (CA) in 5 cases and cryoablation in 2 cases under the guidance of transient entrainment. Transient entrainment during common atrial flutter by pacing from the mid or low lateral right atrium (LLRA) revealed a long conduction time between the LLRA and the orifice of the coronary sinus (CSo) (73% to 121% of flutter cycle length). In 2 cases, fragmented electrograms were recorded at the low right atrial septum with durations of 150 msec and 155 msec, respectively. Because these fragmented electrograms were transiently entrained by rapid atrial pacing in the same manner as other atrial electrograms and were recorded in an area of long conduction, we believe that fragmented electrograms represent critical slow conduction. In 5 cases, CA was directed at this area. Three cases were successfully treated with 3 to 4 DC shocks of 100 J (follow up periods of 11.3, 4.5 and 3 months). Two cases which received 1 to 2 DC shocks of 100 J had recurrence of atrial flutter 6 and 4.7 months later, respectively. Two cases which showed atrial septal defect received surgical treatment. They were successfully treated with extended cryoablation in this same area (follow up periods of 26 and 9.2 months). In conclusion, extended ablation of an area of fragmented electrograms using transient entrainment may be an effective treatment for common atrial flutter. PMID- 8464143 TI - A case report of isolated levocardia without intracardiac anomalies associated with sick sinus syndrome. AB - A 42-year-old female with cardiomegaly showed bradycardia without syncope. Clinical data showed that she had an isolated levocardia with interruption of the inferior vena cava. Isolated levocardia was defined as a normally placed heart associated with situs ambiguus of other viscera. She did not have intracardiac anomalies. Isolated levocardia without intracardiac anomalies, as in this case, has only been reported in 13 other cases. Isolated levocardia is often accompanied by severe complex intracardiac anomalies and, therefore, most of the patients have a short life span. Situs ambiguus, especially left isomerism, is frequently associated with deteriorated sinus node function, and an interruption of the inferior vena cava may also be an indication of this phenomenon. Therefore, the patient's sinus node function was examined using an electrophysiological study and a 24-hour ambulatory electrocardiogram. Sick sinus syndrome was finally confirmed. PMID- 8464144 TI - [Molecular epidemiology of hepatitis A virus]. AB - The genome of hepatitis A virus (HAV) is a linear plus-strand RNA molecule of 7,500 nucleotides and it shares common strategies of construction and function of the picornavirus family. Since it has a unique nucleotide sequence homology, HAV has been classified in the genus of hepatovirus, newly added to the family. Nucleotide sequence of the putative VP1/2A junction area was found variable and a 168 nucleotide portion of the region has been compared with many HAV sequences obtained from all over the world. It was found that HAV strains could be identified and classified into 7 genotypes or 9 subgenotypes. Analyses of the nucleotide sequence homology of this particular region is useful, not only in the study of epidemiology of hepatitis A, but also in the study of the molecular epidemiology of HAV. PMID- 8464145 TI - [Molecular evolutionary analysis of hepatitis B virus (HBV) and genetic classification]. AB - HBsAg of Hepatitis B virus (HBV) has been classified into four major subtypes (adw, adr, ayw, ayr) by the serological methods. Using molecular evolutionary analysis technique, we constructed the phylogenetic tree for the partial S gene (HBsAg gene) of HBV. The tree shows that 51 strains of HBV can be classified into following four genetic subgroups: (1) strains of subtypes ayw and adyw, (2) those of adw and adr, (3) another of adw, and (4) other subgroup of adr, adw, ayr, ar and ad. We propose that these subgroups be designated gyw, gdw-1, gdw-2, and gdr, respectively, with "g" standing for genetic classification. It is important that the genetic classification of HBVs is not always compatible with conventional serological subtypes. It is possible that the conventional subtypes do not represent a classification according to the degree of genetic difference among strains of HBVs. Thus, our genetic classification is more suitable for studies of epidemiological and virological features of HBVs. PMID- 8464146 TI - [Mutation in core and pre-core amino acid sequences of hepatitis B virus correlate with fulminant and severe hepatitis]. AB - Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as, an asymptomatic chronic carrier state. To investigate why an extreme immunological attack occurs in fulminant hepatitis and severe exacerbation, the entire precore and core region were sequenced in 13 subjects. No significant change was noted in the 6 self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of core codons #84 to #99 were found in all 7 fulminant and severe exacerbation patients. These data suggest that this mutation clustering region may play an important role in the pathogenesis, and such mutations appear to be related to severe liver damage. PMID- 8464147 TI - [Association of pre-core defective HBV mutant with anti-HBe positive chronic hepatitis]. AB - Precore defective HBV mutant has been suggested to be responsible for the pathogenesis of fulminant hepatitis. This variant is unable to produce HBeAg because of the presence of a novel translational stop codon at the end of the precore region of the genome. We examined the precore region of the HBV nucleotide sequence in 12 Japanese anti-HBe positive chronic hepatitis patients in order to ascertain whether the genome has stop-codon mutation in the precore region. Precore defective HBV mutant was found in most of the examined cases. A few cases had a mixture of strains, wild type and precore defective HBV mutant. The variety of precore genome concerned with the pathogenesis of chronic hepatitis still needs to be clarified. PMID- 8464148 TI - [The point mutation of pre-C region HBV-DNA in sera from chronic hepatitis B]. AB - To clarify the relationship between a point mutation of HBV-DNA Pre-C region and the serological feature of chronic hepatitis B, we determined the Pre-C region sequence of HBV-DNA obtained sera of 39 patients with chronic hepatitis B. The screening of the gene arrangement of Pre-C region of HBV-DNA was performed by a direct sequence method amplifying HBV-DNA by polymerase chain reaction methods. In 22 of HBeAg positive cases, a mutant type (the 28th codon changed from TGA to TAG: stop codon) was found in only one case. The other hand, In 17 of HBeAg negative cases, it was found in 6 cases with fluctuating ALT and DNA-polymerase levels. We concluded that mutant viral infections could be the main cause of HBeAg negative cases with fluctuating ALT and DNA-polymerase levels. PMID- 8464149 TI - [Defective short variants of S region in chronic HBV carriers]. AB - We analyzed the pre-S and S region of hepatitis B virus by polymerase chain reaction in 60 chronic carriers. In 10 hepatitis B e antigen-positive chronic carriers, a single DNA band was detected at the expected size, whereas additional shorter DNA bands were observed in some cases with chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The smaller-sized DNA bands from chronic hepatitis patients had the deletion of 183 bp in the pre-S gene, and the deletion of 492 bp in S gene. The reasons of the appearance of these mutants are unknown, but it may be interesting to study in relationship to the mechanism of host immune response. PMID- 8464150 TI - [Heterogeneity of delta virus RNA sequences in Japan]. AB - Hepatitis delta virus RNA sequences were determined in isolates from two Japanese patients, M and S, by polymerase chain reaction and direct nucleotide sequencing and compared with three isolates from Italy, USA and Taiwan. The sequence obtained for hepatitis delta virus RNA from patient M was 92-96% identical to the sequences obtained for three other strains of hepatitis delta virus, whereas the sequence of hepatitis delta virus RNA obtained from patient S was approximately 80% identical to the other sequenced strains. This suggests that the delta agent in Japan has a heterogeneous origin and the delta virus RNA sequence from Japanese patient S is the most divergent delta virus isolate yet analyzed. PMID- 8464151 TI - [Cloning and sequencing of cDNA of the hepatitis E virus genome--application to diagnosis]. AB - Hepatitis E is endemic, often provoking epidemics in many developing countries. The hepatitis E virus has been molecularly cloned and sequenced and has a single stranded, positive-sense RNA genome, 7,194 nucleotides, followed by a poly(A) tail. There are three open reading frames. The non-structural gene, approximately 5 kb, is located at the 5' end, while the structural gene, approximately 2 kb, is located at the 3' end of the genome. There is low level nucleotide variation among hepatitis E virus strains isolated from Myanmar and China. PMID- 8464152 TI - [Recent progress in molecular biology of chemically-induced hepatic carcinogenesis]. AB - Chemically-induced hepatic carcinogenesis is a suitable model to investigate multistep process of carcinogenesis, because preneoplastic and neoplastic lesions develop in a sequential manner. The process is initiated by emergency of "genetically altered cells" or "initiated cells" which have a potential to progress to hepatocellular carcinomas. The cells can clonally expand under the effect of tumor promoters or carcinogens. Clonal expansion will increase the probability that a cell undergoes further genetic changes. By this stepwise manner, a cell may acquire neoplastic properties such as independence to growth factors, invasive growth, loss of antigenicity, metastatic capacity, etc. The author reviewed the recent advance in studies on oncogenes, tumor suppressor genes and growth factor genes concerning to rodent hepatic carcinogenesis. PMID- 8464153 TI - [Genotypes of alcohol dehydrogenase and aldehyde dehydrogenase and their significance for alcohol sensitivity]. AB - Genotypes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) loci were determined, using allele specific oligonucleotides. Gene frequencies of ADH2(1) and ADH2(2) were 0.29 and 0.71, respectively, in the Japanese control group. No significant difference was found in the ADH2 genotype between the patients and the control group. Gene frequency of ALDH2(1) and ALDH2(2) were 0.65 and 0.35 in the control group, while 0.93 and 0.07, respectively in the patient group. Most of the patients, 20 out of 23, were homozygous Caucasian type. All individuals with homozygous atypical ALDH2(2)/ALDH2(2) and most of those with heterozygous atypical ALDH2(1)/ALDH2(1) were alcohol flushers, while all of the usual ALDH2(1)/ALDH2(1) were nonflushers. The results indicate that Japanese with the atypical ALDH2(2) allele are at a much lower risk in developing alcoholic liver disease than those with usual ALDH2(1)/ALDH2(1), presumably due to their sensitivity to alcohol intoxication. PMID- 8464154 TI - [ADH 2, 3 and ALDH 2 gene frequency in Japanese alcoholics]. AB - To elucidate genetic susceptibility to alcoholic liver injury (ALD), polymerase chain reaction (PCR) method assay was developed to detect point mutations in each gene and gene frequency in various liver diseases was studied. It was shown previously that ALDH2(1) gene was more frequently found in patients with ALD (confirmed in this study), probably because they are able to consume too much alcohol (non-flushing type). This study revealed that, in addition to this ALDH heterogeneity, ADH heterogeneity may correlate with the severity of alcoholic liver injury, especially in those was low ADH activity and tend to have severe damage. PMID- 8464155 TI - [Apolipoprotein A-I, E, C-III and LDL-receptor mRNA expression in liver diseases]. AB - The liver plays a major role in lipid metabolism, and quantitative and or qualitative changes in serum lipoproteins and apolipoproteins have been observed in various liver diseases. We investigated changes in hepatic mRNA expression of apolipoproteins A-I, C-III, and E and LDL receptor in human liver diseases, rat D galactosamine, CCl4 induced liver failure and regenerating liver. The apolipoprotein mRNA expression were significantly decreased in liver and severe acute hepatitis as compared with controls and were correlated with serum albumin levels. LDL receptor mRNA expression were decreased in liver cirrhosis and rat liver failure. These findings indicated that liver biosynthesis of these apolipoproteins and LDL receptor are suppressed in liver disease. On the other hand, LDL receptor mRNA expression increased in regenerating liver, and this shows that serum cholesterol was needed for membrane biosynthesis. PMID- 8464156 TI - [Molecular biology in development of fatty liver--regulation of apolipoprotein B synthesis]. AB - Apolipoprotein B (apo B) synthesis in fatty liver was described in this review. Apo B synthesis has not been intensively studied in fatty liver. Recently, we demonstrated that hepatic apo B mRNA level increased in two experimental models of fatty liver. Davidson et al. reported that apo B mRNA editing was enhanced in fatty liver induced by refeeding after fasting. However, further investigation is needed to clarify whether alteration in apo B gene regulation participates in development of fatty liver. PMID- 8464158 TI - [Expression of the protein kinase C genes during liver regeneration]. AB - Protein kinase C (PKC) plays an important role in intracellular signaling. PKC consists of a family of at least eight distinct enzymes. How PKC can be responded to liver regeneration and growth is largely unknown. In an in vivo experiment, regenerating liver after partial hepatectomy (Hx) and carbon tetrachloride (CCl4) administration, expression of the PKC alpha-type was increased, with a single peak, after Hx and CCl4 administration. On the other hand, the PKC epsilon-type gene was activated with biphasic peaks following Hx but was elevated with a single peak after the CCl4 administration. In an in vitro experiment using primary cultured hepatocytes, both of the PKC alpha-type and epsilon-type genes could be induced only by combination of insulin and serum. These results demonstrate that both isoforms of PKC are identically regulated by extra- and intracellular stimuli, thereby influencing growth control of hepatocytes. PMID- 8464157 TI - [Gene expression of MMPs and TIMPs in the process of hepatic fibrosis]. AB - The matrix metalloproteinases (MMPs) gene family includes MMP-1 (interstitial collagenase), MMP-2 (72 kD type IV collagenase/gelatinase), MMP-3 (stromelysin/transin), MMP-7 (putative MMP; pump-1), MMP-8 (granulocyte collagenase) and MMP-9 (92 kD type IV collagenase/gelatinase). This gene family has the common characteristics in the gene structure as follows: All of MMPs have the active site metal ion-binding domain. All six enzymes are activated with the concomitant removal of N-terminal segment of the latent enzyme. The removed segment contains an unpaired cystein residue within the conserved amino acid sequence PRCGVPDV, located immediately adjacent to the proenzyme cleavage site. The authors showed the gene expression of MMP-1 in the process of hepatic fibrosis. The remarkable expression was noted on fibroblasts and macrophages within the newly-formed fibrous bands with lots of infiltrated lymphocytes. Liver cirrhosis did not showed the positive dots of MMP-1 mRNA. On the other hands, the expression of TIMP reported by Takahara et al., revealed the high level of expression in the advanced fibrosis. PMID- 8464159 TI - [Amyloidosis and hepatic amyloidosis]. AB - The classification of amyloid and amyloidosis has undergone several revisions. The 1990 revision of the nomenclature at the 6th Internal Symposium on Amyloidosis in Oslo has been widely accepted and the basis for nomenclature and classification is the fibril protein making up the amyloid deposits. The liver is a major site of amyloid deposition in the disseminated form of the disease. Many studies have shown that the morphologic distribution of amyloid within the liver is not a reliable method for distinguishing AA from AL amyloidosis. PMID- 8464160 TI - [Recent studies on Ito cells with molecular biology]. AB - By Northern blot analysis of total RNA, extracted from normal human and rat Ito cells, either freshly isolated or in culture, recent studies demonstrated the expression of mRNA for collagen type I, III, IV, fibronectin, laminin, transforming growth factor-beta (TGF-beta), hepatocyte growth factor, nuclear retinoic acid receptor-beta and alpha-smooth m muscle actin. Moreover, Ito cells isolated from experimentally induced fibrotic livers exhibited a marked increase in mRNA for collagen type I, associated with a moderate increase in mRNA of collagen type III and TGF-beta. Although endothelial cells from the same liver also showed moderate increase in mRNA for collagen type I alone, hepatocytes showed no changes. From these results it is concluded that Ito cells are the most important cells in hepatic fibrogenesis. PMID- 8464161 TI - [Molecular defects in familial LCAT deficiency]. AB - Lecithin: cholesterol acyltransferase (LCAT) is the enzyme that catalyzes the esterification of free cholesterol in plasma lipoproteins. Familial LCAT deficiency, which is a rare hereditary disorder of lipid metabolism, inherited as an autosomal recessive trait, is characterized by corneal opacity, anemia and frequently, though not invariably, renal failure. Recently, LCAT cDNA and gene have been cloned. Studies on DNA samples from unrelated patients with familial LCAT deficiency and fish eye disease, which is characterized by severe corneal opacity alone, revealed both diseases to be caused by respective mutations of the LCAT gene. It is suspected that defect or functional abnormality of LCAT, caused by these genetic defects, underlie the various clinical and biochemical characteristics observed in LCAT deficiency or fish eye disease. PMID- 8464162 TI - [Gene analysis of human cholinesterase variants]. AB - People with genetic variants of cholinesterase (ChE) have been reported to have prolonged apnea with the use of myorelaxant succinylcholine. For the silent type variant ChE, two cases of mutation have been reported. In one case, the exon 2 of ChE gene was disrupted by a 342 bp insertion of Alu element. In the other case, a frame shift mutation was identified at Gly-117 (GGT-->GGAG) to create a stop codon at nucleotide 384. Dibucaine resistant ChE was examined and found to have a point mutation at nucleotide 209 (A-->G) that converted Asp-70 to Gly, and consequently reduced the affinity of ChE for choline esters. In addition, another two types of a point mutation reducing ChE activity were reported on K variant (Ala-539-->Thr) and a case of (Gly-365-->Arg) in a patient with liver cirrhosis. PMID- 8464163 TI - [Genetic analyses of alpha 1-antitrypsin deficiency]. AB - The deficiency of alpha 1-antitrypsin, a strong protease inhibitor, is known to cause pulmonary emphysema, neonatal hepatitis and liver cirrhosis. Among 75 variants reported so far, amino acid or DNA variations have been determined in about 30 variants. Many are caused by single base substitutions which then cause single amino acid replacements. In most of the null variants, base substitutions, base deletions or base insertions make stop codons appear somewhere beyond the mutation sites, which cause truncated proteins. Only several variants, including PiZ and PiMmalton, characterized as having cytoplasmic globules in hepatocytes, cause liver diseases. Recent analyses on the tertiary structure of alpha 1 antitrypsin have elucidated the mechanism of the formation of insoluble polymers in PiZ patients. The accumulation theory seems more relevant to the mechanism of the liver damage than the protease-antiprotease imbalance theory. PMID- 8464164 TI - [Molecular basis of urea cycle disorders]. AB - Five different enzymes, carbamyl phosphate synthetase I (CPS I), ornithine transcarbamylase (OTC) argininosuccinate synthetase (AS), argininosuccinate lyase (AL) and arginase (AR) play a role in urea synthesis from ammonium. The structures of cDNA of all these enzymes and those of genome DNA of some enzymes (OTC, AL, AR) have been already clarified, and using of the information, the alleles of each enzyme deficiency have been identified. Alleles are extremely heterogeneous in all enzyme deficiencies, in sharp difference from other inborn errors of metabolism, such as cystic fibrosis and hemoglobinopathies. PMID- 8464165 TI - [Hepatitis and hepatocarcinogenesis in the transgenic mice]. AB - Persistent hepatitis B virus (HBV) infection is epidemiologically closely associated with the development of human hepatocellular carcinoma (HCC). A molecular mechanism that would explain the strong epidemiological link of persistent HBV infection with HCCs is still open to debate. Among HBV carriers, HCC develops only in patients with chronic liver disease, such as chronic active hepatitis, liver fibrosis, or liver cirrhosis. In other words, hepatitis-related proliferative changes, which are mainly sustained by repeating cycles of cell death and regeneration either immunologically or through virus infection, appear important for HBV hepatocarcinogenesis. The same mechanism may also be present in human hepatitis C virus-related hepatocarcinogenesis. In this article, I reviewed animal models of HBV-related hepatocarcinogenesis. It is important to evaluate and check whether the animal models are fit with human HBV hepatocarcinogenesis or not. PMID- 8464166 TI - [The establishment of a monolayer culture system of guinea pig chief cells and an enzyme immunoassay system for guinea pig pepsinogen]. AB - For the purpose of studying pepsinogen secretion from gastric chief cells, we established a monolayer culture system of guinea pig chief cells and an enzyme immunoassay (EIA) system specific for guinea pig pepsinogen. Dispersed chief cells were obtained from gastric mucosa of a guinea pig using collagenase, GEDTA, and Percoll solution, suspended in DMEM/F-12 (1/1 containing 10% FCS) media, and cultured for 70hr. Then the monolayer culture system was established. Pepsinogen was purified from gastric mucosa of a guinea pig using DEAE-Sephacel and Sephacryl S-200 columns. Antibody to pepsinogen was raised by immunizing rabbit with the purified pepsinogen. A two-site EIA system was then established using beta-galactosidase-labeled Fab' antibody. The EIA system showed sensitivity to measure above 1.5ng of guinea pig pepsinogen, and the monolayer culture system responded well to secretagogues. These systems are useful for studying pepsinogen secretion. PMID- 8464167 TI - [The effect of prostaglandin E1 and prostaglandin F2 alpha in the ischemic small intestine of dogs]. AB - The effect of PGE1 and PGF2 alpha in the ischemic intestinal tract were examined. In 40 mongrel dogs, we studied ischemic models of small intestine. PGE1 or PGF2 alpha was injected into the anterior mesenteric artery after reperfusion according to each occlusion time, and the tissue blood flow was measured on both mucosal and serous sides of small intestinal loop by laser flowmeter to examine the relation to the extent of tissue damage. Tissue blood flow of the ischemic intestine after the injection of PGE1 increased by 148-208% in the 3-5 hr occlusion group and by 86-110% in the 7-10 hr occlusion group. Tissue blood flow after the injection of PGF2 alpha decreased by 39-59% in the 3-5 hr occlusion group and by 1-15% in the 7-10 hr occlusion group. These results indicate that the effect of PGE1 and PGF2 alpha in the ischemic intestine would be available up to 3-5 hr of ischemia. Histological examination revealed that viability of the remaining crypt was high in the PGE1 injection group but low in the PGF2 alpha injection group. These findings suggest that PGE1, if try at the early stage, would be effective for the treatment of ischemic lesion. PMID- 8464168 TI - [The long-term follow-up study of Japanese patients with ulcerative colitis]. AB - To elucidate the long-term outcome of the ulcerative colitis we analyzed 124 patients suffering for more than 10 years concerning the long-term prognosis, cumulative rate of colectomy, cumulative risk of cancer development and cumulative survival rate. Long-term prognosis were divided to three categories as good, fair and poor, according to present disease activities, social availability and subjective judgement. One hundred and twenty four patients were divided to 66 patients with good prognosis, 27 fair and 31 poor (2:1:1). The rate of patients having active disease at each year were followed-up annually for 10 years according to final three categories of the prognosis. The serial curve of annual rate of having active disease of the patients with poor prognosis was the highest, fair prognosis the second, good prognosis the lowest. The factors affecting the final prognosis were the period before initiation of proper treatment, the severity of the first attack or the elder age (> 40 year old) at the first attack. Twenty six patients were undergone colectomy in relation to ulcerative colitis. The cumulative colectomy rate was 16.5% at 10 years and 38.5% at 15 years after the onset. Malignant disease or severe dysplasia of the colon developed in 4 patients 10 to 14 years after the onset. Cumulative survival rate was equal to the expected survival curve during 16 years. The main causes of death were intracranial hemorrhage and colorectal malignant disease. PMID- 8464169 TI - [Plasma cholecystokinin levels in rats with pancreatic insufficiency induced by intra ductal injection of oleic acid]. AB - Plasma cholecystokinin (CCK) levels in rats with pancreatic insufficiency induced by a single injection of 50 microliters oleic acid into the pancreatic duct were determined by a sensitive and specific bioassay using the isolated rat pancreatic acini. Treatment with oleic acid significantly decreased pancreatic wet weight within 7 days, which lasted until the end of observation (56 days). Histologic examination revealed the destruction of acinar cells and the epithelium of intra- and interlobular ducts. Plasma CCK bioactivity was significantly increased from the pre-treatment values of 0.8 +/- 0.1pM to 5.1 +/- 1.4pM at 24h after oleic acid treatment. After this peak, plasma CCK levels gradually decreased. Even after 56 days, however, plasma CCK levels in oleic acid-treated rats were significantly high compared with those in control rats. In the present study, plasma CCK levels in rats with chronic pancreatitis did not correlate with the progress of pancreatic insufficiency. PMID- 8464170 TI - [A case of gastric malignant lymphoma occurred subsequent to idiopathic thrombocytopenic purpura]. PMID- 8464171 TI - [A case of hematological metastatic tumor of the liver from sigmoid colon cancer]. PMID- 8464172 TI - [A case of Yersinia enterocolitis diagnosed by culture of the biopsy specimen taken through colonofiberscope]. PMID- 8464173 TI - [Interstitial pneumonitis associated with ulcerative colitis: a case report and review of the literature]. PMID- 8464174 TI - [Follow-up study of a case of hepatic angiomyolipoma, after established diagnosis by ultrasonography-guided aspiration biopsy]. PMID- 8464175 TI - [A case of gallbladder cancer associated with cholesterolosis within the cancer region]. PMID- 8464176 TI - [Effect of TUDCA for cholestatic reaction due to serum in patient with primary biliary cirrhosis]. PMID- 8464177 TI - [Analysis of proliferative activity in gastric biopsy specimens by combined BrdU and DNA polymerase alpha immunohistochemistry]. AB - To evaluate correctly the proliferative activity of tumor cells, it is necessary to clarify not only S-phase fraction but also the growth fraction of tumor tissues. We used combined BrdU and DNA polymerase alpha (pol-alpha) immunohistochemistry to gastric biopsy specimens, and analyzed the proliferation of the neoplastic lesions of various degrees of malignancy. The results were as follows: The distribution of pol-alpha positive cells were almost the same as that of BrdU positive cells, but the percentage of pol-alpha positive cells was higher than that of BrdU positive cells irrespective of the mucosal specimens. In the adenomas, both BrdU and pol-alpha positive cells distributed generally superficially in the mucosal layer. In the well differentiated adenocarcinomas, both BrdU and pol-alpha positive cells distributed diffusely in the deeper layer of the mucosa. The ratio of the number of BrdU positive cells to that of pol alpha positive cells, which means the S-phase fraction in the growth fraction, was higher in the tumor and that higher in the well differentiated adenocarcinomas than that of the adenomas. In conclusion, the combined BrdU and pol-alpha immunohistochemistry in gastric biopsy specimens are useful to evaluate the degree of malignancy. PMID- 8464178 TI - [An efficient method for quantification of Helicobacter pylori in biopsy specimen using PCR]. AB - A procedure for the detection and quantification of Helicobacter pylori in gastrointestinal tissue biopsy specimens by polymerase chain reaction (PCR) is presented. This method provides an accurate quantitative and sensitive measurement of the amount of H. pylori in the gastrointestinal tract without cultivation of this microorganism. We have used 30 cycles of PCR in the presence of 3.5mM Mg++ and demonstrated that the DNA content of one H. pylori cell is 0.0076pg. Using this approach, we analyzed samples of gastrointestinal tissue biopsies from 10 patients with various gastrointestinal disorder. Each of these patients had detectable H. pylori at levels ranging from 0.10 to 60.61 cells for each tissue cell. This new technique thus provides a useful way to detect H. pylori in gastrointestinal tissue biopsy specimens. PMID- 8464179 TI - [Modern trends of treatment in male infertility]. PMID- 8464180 TI - [A simple renal cyst]. AB - Incidence of simple renal cysts was calculated in 30,316 patients receiving routine ultrasound examination in one hospital, and 170 cases visiting Chiba University Hospital were further analyzed in terms of their clinical features. Incidence of simple renal cyst was 14% in all populations and ratio of male to female was 1.6:1. Patients age ranged from 8 to 92 years (average age 58.6 years) and number of a renal cyst was increased after fifth decade in both sexes. Patients of Chiba University Hospital were examined on symptoms and clinical courses with maximal follow up to 132 months (average 18 months). Symptoms associated with simple renal cysts were: none (75.3%) pain (14.7%) and gross hematuria (6.4%). Urinalysis of patients without associated urinary diseases, showed microhematuria in 40% and proteinuria in 12%, however, grade of microhematuria and proteinuria was not correlated with size of cysts. Number of cysts tended to increase with age. Size of cysts and rate of enlargement were increasing along with age. In any cases, renal function was not and affected nor occurred malignant tumor during follow-up period. Cyst punctures with sclerosing agent were performed in 16 patients, and most of the cysts remained the same as or exceeded their original size. It is concluded that routine follow-up is sufficient in most cases without symptoms, since simple renal cysts increase slowly, and impairment of renal function and progression to malignant tumors do not occur. PMID- 8464181 TI - [Morphological investigation of external sphincter muscle of the male posterior urethra]. AB - For investigation of function of the male posterior urethra, morphological study was performed in terms of the muscle architecture including sphincter muscle of the posterior urethra. The muscle localization was demonstrated by microdissection in eight male cadavers. Histological examination was also employed with HE staining and immunohistochemical method to detect the nature of these muscles. At the dorsal side, the muscle fibers of the deep trigone were located from the inter-ureteral ridge beyond the bladder neck to the vermontanum surrounding the posterior urethra. They were regarded as the internal urethral sphincter muscles. At the ventral side, the muscle fibers were also found just outside the ventral prostate running from the base to the apex of the prostate. Then, they were circularly located around the membranous urethra. These saddle shaped muscles were proved to be striated muscle by the immunohistochemical examination using anti-Desmin and anti-Myoglobin antibody. Therefore, the external urethral sphincter muscle would consist of the pelvic floor muscles and the urethral sphincter muscles. PMID- 8464182 TI - [Transrectal hyperthermia for the treatment of chronic prostatitis]. AB - A total of 36 cases with chronic non-bacterial and non-chlamydial prostatitis or prostatodynia underwent 5 weekly, 1-hour sessions of transrectal microwave hyperthermia (43 degrees C) to the prostate. All patients had a long history of the condition and failed to respond to a variety of conventional treatments. The efficacy of the treatment was evaluated by the effects on subjective symptoms and/or on white blood cells in expressed prostatic secretions. Concerning the overall clinical efficacy, excellent results were obtained in 11 (30.6%), good in 8 (22.2%), fair in 8 (22.2%) and poor in 9 (25.2%). Although minor complications were noted in 5 cases (anal pain; 2, hematospermia; 1, hematuria; 1), all cases received full sessions. These results indicated the usefulness of the hyperthermia for this benign condition, which has so far responded poorly to the conventional therapy. PMID- 8464183 TI - [A study of brain MRI findings and clinical response of bladder emptying failure in brain bladder]. AB - In 45 patients (38 males and 7 females; average age: 78 years) with brain bladder, who did not have any peripheral neuropathies and spinal disturbances, cerebral findings of MRI (1.5 T) T2 enhanced image were analyzed in comparison with those of 7 control patients with normal urination after BPH operations. Patients with neurogenic bladder were divided into three groups as follows: 33 patients with a chief complaint of urinary disturbance (Group I), 9 patients with urinary incontinence (Group II) and 3 patients with balanced bladder (Group III). High frequency of lacune (24%) of the globus pallidus and low signalling of the corpus striatum (30%) was found in Group I patients, but low frequency in other Group patients and control patients. Furthermore, pathologic changes with various grade in the globus pallidus were observed in 91% of Group I patients. In the treatment of urinary disturbance, a high improvement rate of micturition disorder (77%) was obtained in patients treated with a combination of dantrolene and TURp (TUIbn for females). However, patients which had clear lacune of the globus pallidus showed the low improvement rate. It should be possible that the globus pallidus contributes to control the movement of the external sphincter and the pelvic base muscles as well as other striated muscles. Moreover, lacune was rarely found in the urination center of the brain-stem on MRI. PMID- 8464184 TI - [The role of lymphocytes and histiocytes as mechanism of action of BCG for bladder cancer]. AB - Antitumor activity of BCG for transitional cell carcinoma of the urinary bladder was evaluated in 103 patients from October, 1983 to October, 1989 at Hirosaki University Hospital. At the same time, the role of various inflammatory cells infiltrating in the bladder wall after intravesical BCG instillation as mechanism of action of BCG was studied. Of 72 patients with superficial bladder cancer, 19 showed a complete response and 28 showed a partial response. The effective rate was 65.3 percent. Significant efficacy was obtained in patients received more than 5 times instillation of BCG. Before intravesical BCG instillation, a small number of lymphocytes or plasma cells infiltrated in the stroma of the tumor. But histiocytes, neutrophils or eosinophils were hardly found. After BCG instillation, the degree of infiltration of each of them tended to increase. The mean degree of infiltration of those inflammatory cells almost all significantly increased in the stroma of the tumor, while only lymphocyte and histiocyte counts significantly increased in both the basal areas of the advancing margin of tumor cells and the tumor free submucosa after BCG instillation. Epithelioid granulomas were recognized almost in the basal areas of the advancing margin of tumor cells and the tumor free submucosa after BCG therapy. Langhans' giant cells were occasionally found within these lesions. In 2 patients marked central necrosis (caseation) was noticed in epithelioid granulomas. In BCG effective cases with superficial bladder cancer lymphocytes and histiocytes increased significantly in all of the stroma of the tumor, the basal areas of the advancing margin of tumor cells and the tumor free submucosa. On the other hand, in BCG noneffective cases they increased significantly only in the stoma of the tumor. Subsets of lymphocytes which increases after intravesical BCG instillation were mainly T pan cells with the predominance of T helper/inducer cells (Th/Ts ratio always > 1). PMID- 8464185 TI - [Effects of testosterone on the autonomic receptor-mediated function in lower urinary tract from male rabbits]. AB - Effects of testosterone on the autonomic receptor-mediated function of the male rabbit urinary bladder and proximal urethra were examined. The alteration of alpha 1-, alpha 2-, beta-adrenergic receptor and muscarinic cholinergic receptor densities in the urinary bladder and proximal urethra were determined by radioligand binding techniques after castration. The density of alpha 1 adrenergic receptor in the proximal urethra decreased gradually after castration. This change was significant 8 weeks after castration. The alpha 2-adrenergic receptor density in the proximal urethra slightly increased after castration, but it was not statistically significant. The beta-adrenergic receptor density in the bladder dome did not change after castration. The density of muscarinic cholinergic receptor in the bladder dome significantly decreased in animals 2 weeks after castration. Additionally, the density of autonomic receptors and the response of muscle strips to autonomic drugs were compared in three age-matched experimental groups: control group, castrated group and castrated and testosterone supplemented group. When the autonomic receptor densities in the castrated group were compared to those of the control, the changes similar to the result in the previous experiment were noted. Testosterone supplementation restored the densities of alpha 1-adrenergic and muscarinic cholinergic receptors in castrated group to control levels. The responses of muscle strips to autonomic drugs closely paralleled the receptor densities. Castration decreased the alpha 1 adrenergic and the muscarinic cholinergic receptor function, however, testosterone restored those function. These findings indicate that testosterone affects the autonomic receptor-mediated function in the smooth muscle of lower urinary tract. PMID- 8464186 TI - [Inhibitory activity of urinary macromolecule upon calcium oxalate crystal aggregation using an aggregometer]. AB - We studied inhibitory activity of urinary macromolecule upon the calcium oxalate crystal aggregation using an aggregometer. We have developed an aggregometric assay method to measure the anti-aggregation ratio of calcium oxalate crystals in vitro. The macromolecular fraction of urine with a molecular weight above 5,000 was isolated by PD-10 (Sephadex G-25M, Pharmacia) and made up to three-fold by Centriprep Concentrator (Amicon). The urinary macromolecular substances of recurrent calcium stone formers showed much less inhibitory activity than those of healthy controls. There were no significant relationships between the anti aggregation activity and the concentration of urinary proteins and other parameters concerning with stone diseases. It was speculated that some proteins, molecular weight about 10,000-30,000, might inhibit the aggregation vigorously based on the result of gel filtration (Superrose 12 HR, 20/50, Pharmacia) technique used in a healthy man's 24 hours urine. Thus, it supports that some urinary macromolecules are important during the phase of aggregation of calcium oxalate crystals, and that the feeble activity to present the aggregation may be one of the cause of calcium oxalate stone formation. PMID- 8464187 TI - [Preoperative embolization using absolute ethanol for renal cell carcinoma- including the questionnaire survey in Japan]. AB - The usefulness of transvascular embolization before radical nephrectomy using absolute ethanol was studied in thirty-two cases with renal cell carcinoma, among them, 30 cases received radical nephrectomy one day after transvascular embolization. And a nation wide questionnaire survey regarding the embolization was also reported. These results were as follows: 1. The infarcted areas were very extensive and among 28 cases examined, 26 cases showed more than 75% of infarct in the whole area of the cortex. 2. Among 32 cases, 22 cases complained of no pain after the embolization using absolute ethanol only by the preventive epidural administration of analgesics. 3. The questionnaire survey showed that the embolization before radical nephrectomy was performed in 62% of the hospitals as a whole, including 81 hospitals (41%) in which the embolization was performed case by case. In the whole of hospitals, 21% performed the embolization principally by evaluating the significance of the embolization. On the other hand, 19% of the hospitals did not perform by the reason of no significance of the embolization on the treatment of renal cell carcinoma. As shown in this questionnaire survey, the significance of the embolization before radical nephrectomy was still debatable in our country. 4. In 62% of the hospitals where the embolization is carried out, as a whole, the period from embolization to the nephrectomy was 3-7 days. And in 42% of the hospitals as a whole absolute ethanol was principally used as an embolizing agent. In conclusion we believe that absolute ethanol was useful and should find further application as an embolizing agent before the radical nephrectomy. PMID- 8464188 TI - [Subpopulation of leucocytes in the semen from fertile and infertile men- immunohistochemical and flow-cytometric analysis]. AB - It is hard to differentiate leucocytes from immature germ cells among many round cells in ejaculated semen. Recently monoclonal antibodies (MoAbs) which recognize surface antigen of various subtypes of leucocytes are available. In this study we applied a panel of MoAbs for leucocyte subpopulations (granulocytes, T lymphocytes, B-lymphocytes, Monocytes/Macrophages and pan-leucocytes). Semen smears from 64 mild oligozoospermic patients and 5 fertile volunteers were stained by immunohistological technique (avidin-biotin-immunoperoxidase method). We found highly varying total leucocyte numbers ranging from 1200 to 2.2 x 10(8) per ejaculate. When comparing semen from infertile patients with those from fertile donors, statistically significant higher medians of total leucocytes, total granulocytes and monocytes/macrophages were seen in infertile group. We compared a total number of leucocytes obtained from conventional Papanicolaou staining with that from immunohistochemical staining. Both were almost identical but the former gave a little bit higher value, because of the difficulty in differentiating leucocytes from immature germ cell by Papanicolaou staining. Moreover we performed an experiment to evaluate the applicability of flow cytometry (FCM) to count leucocytes in semen. Cells in the semen smears were stained with MoAbs recognizing the surface antigen shared by every leucocyte, and percentage of the leucocytes which were thus stained with MoAbs was compared with that determined by FCM. Results from FCM constantly gave lower value than these from immunostaining. This is probably because FCM could not differentiate leucocytes from contaminated non cell substances (e.g. cell debris). From the present study it is not adequate to use FCM for the detection of leucocytes in semen as applied in haematology. Further techniques to remove non-cellular substances should be established for its application in semen analysis. PMID- 8464189 TI - [A study on cathepsin B-like substance in patients with urological cancer]. AB - Cathepsin B is a lysosomal cysteine proteinase which is thought to regulate intracellular protein metabolism. In the present study, cathepsin B-like activity was determined in the urine of 53 patients with renal cell carcinoma, 22 patients with urothelial carcinoma and 41 control subjects. In addition, immunohistochemical study of cathepsin B was performed in specimens obtained from 20 patients with renal cell carcinoma, 59 patients with bladder carcinoma and 20 patients with renal pelvic and ureter carcinoma by using sheep anti-human liver cathepsin B antibody. Cathepsin B-like activity was higher in the urine from patients with renal cell carcinoma or urothelial carcinoma than in that from controls. Positive reactions for cathepsin B were found in 18 of 20 patients with renal cell carcinoma, in 37 of the 59 patients with bladder carcinoma and in 14 of the 20 patients with renal pelvic and ureter carcinoma. In patients with urothelial carcinoma high rates of positive reaction for cathepsin B were observed in patients with advanced stage tumors, with INF gamma-type tumors and with metastatic lesions. In patients with renal cell carcinoma, there was no correlation between the rate of positive reaction and pathological findings. These results indicate that urinary cathepsin B-like activity is higher in patients with urological cancer and that a highly positive reaction for cathepsin B is a risk factor for tumor invasion, metastasis and poor prognosis in patients with urothelial carcinoma. PMID- 8464190 TI - [A case of bladder carcinoma representing leukemoid reaction]. AB - A 60-year-old male with locally invasive bladder carcinoma (pT4 pNo Mo) had a remarkable leukocytosis of 64,900/mm3 in the peripheral blood count without any findings of inflammatory disease. The grade 3 transitional cell carcinoma (TCC) measuring 60 by 58 mm involved the prostate, but radiological examinations including abdominal CT scan and isotopic bone scan failed to prove distant metastasis. Serum calcium level was within normal level. Negative bone marrow finding for leukemia strongly suggested a leukemoid reaction by the bladder carcinoma. Preoperative arterial chemoembolization utilizing mitomycin C microcapsules and cisplatin infused into the tumor feeding arteries provided a normalization of leukocyte count (8,200/mm3) in association with a substantial tumor reduction, and was followed by radical cystoprostatectomy. Although the leukocyte count maintained a normal range for 2 months postoperatively, leukocytosis recurred and rapidly progressed to a leukocyte count of 51,300/mm3. CT scan revealed intrapelvic tumor recurrence, and serum analysis for granulocyte colony stimulating factor (G-CSF) demonstrated an elevated value of 130.9 pg/ml (normal, less than 30 pg/ml). The patient is now on systemic chemotherapy. The laboratory data and the response to the treatments would indicate that the leukocytosis in this patient is a leukemoid reaction due to the bladder carcinoma which may release G-CSF. Ten cases of bladder tumor representing leukemoid reaction have been reported in the literature. PMID- 8464191 TI - [Pelvic fibromatosis simulating urachal tumor--a case report]. AB - We report a case of pelvic fibromatosis, which has been rarely found. A 36-year old man referred to our hospital complaining of right abdominal pain and a swelling mass. Abdominal CT and transabdominal echogram revealed a tumor contacted to the bladder. A nonpapillary tumor (little finger sized) at the bladder dome was observed by cystoscopy, and the tumor was clinically considered as urachal tumor. Wide radical excision including the bladder and prostate was performed. Pathological diagnosis was pelvic fibromatosis arising from musculoaponeurotic structures in the pelvis: The fibromatosis is benign nonmetastatic tumor but the recurrence rate is considerably high. However, in the present case, 14 months after operation there is no recurrence yet. PMID- 8464192 TI - [A case of an infant on continuous ambulatory peritoneal dialysis who markedly improved in subjective symptoms after total parathyroidectomy and autotransplantation]. AB - Total parathyroidectomy and autotransplantation to treat secondary hyperparathyroidism (SHP) have been often performed on adult patients with a favorable result, but have rarely been reported in the pediatric literature. We performed the above operations on a 4-year-7-month girl who was treated by continuous ambulatory peritoneal dialysis (CAPD). The postoperative levels of serum calcium remained low in spite of oral calcium and Vitamin D3 medication, and intravenous calcium administration. But an administration of calcium into CAPF fluid has been maintained the normal level of serum calcium. A calcium balance study conducted for 3 days starting the 24th postoperative day showed 391 mg/day of calcium absorption. The girl obtained a relief from the bone pain approximately 2 weeks after the operation and was able to run easily one and a half month after the operation. Total parathyroidectomy and autotransplantation were considered to be an effective treatment for severe symptoms of osteodystrophy in infantile patients with chronic renal failure. PMID- 8464193 TI - [Findings of combined ventilation/perfusion scintigraphy in children with abnormalities of the bronchi, the lung and lung blood vessels]. AB - Combined ventilation/perfusion scintigraphy with 133Xe/99mTc-HAM was performed within the framework of bronchological diagnostics in 38 children suffering from malformations of the bronchi, lungs and pulmonary vessels, and in 9 children after surgery of hernia of the diaphragm. The findings in stenoses, cysts in the bronchial system and in children with pulmonary vessel malformations, in one child with pulmonary agenesia and in a few other malformations, are presented. The significance of these findings in bronchological diagnosis in case of pulmonary malformations or clinical follow-up is discussed. Combined ventilation/perfusion scintigraphy is a valuable contribution to preliminary diagnosis and in follow-up of children with pulmonary malformations. PMID- 8464194 TI - [New aspects of therapy of mucoviscidosis (CF)]. AB - The authors survey of recent advances in CF research and their therapeutic implications: 1. the possibility of successful gene therapy by transfer of the normal gene to airway epithelial cells. 2. inhalations with the potassium-sparing diuretic amiloride that diminish the viscosity of the bronchial secretions, 3. application of adenosine or uridine triphosphate (ATP or UTP) to the apical surface of the respiratory epithelial cells which intervene with the function of ion channels, 4. enzymatic cleavage and liquidification of bronchial secretions by aerosolized human recombinante DNase. In addition, the possible advantages of (heart-) lung-transplantation are also discussed. PMID- 8464195 TI - [Treatment strategy in childhood bronchial asthma]. AB - Although bronchial asthma is the most frequent chronic disease in childhood, not all of the affected children are readily recognised as asthmatics well in time for appropriate treatment. Since most of the children can get rid of the symptoms if all the available treatment methods are made use of systematically, early diagnosis and correct estimation of the disease pattern are essential for good long-term prognosis. New pathogenetic knowledge on the importance of inflammatory processes affecting the bronchial mucosa has definitely shifted the points of emphasis in asthma treatment as is evident from the international consensus recommendations. Focus of drug therapy is on prophylactic antiphlogistic treatment. Only in cases of severe asthma continual bronchodilatory medication is also recommended. The inhalative route is beneficial and feasible for all age groups. Long-term treatment, wherever necessary, also includes continual medical supervision in consultation with a paediatric pneumologist. PMID- 8464196 TI - [Normalization of HBA1--a realistic therapeutic goal?]. AB - Optimal regimen for therapy should lead to near-normal glycaemia in children with diabetes mellitus. Therefore normal or near-normal values of glycated haemoglobin (HbA1) during long periods seem to be very important for the assessment of the quality of metabolic control. However, reports published so far indicate that this goal for paediatric diabetology is currently not achieved in a considerable number of patients. We report on the results of HbA1-estimations in 76 children with diabetes mellitus during a one-year period. We found in 14 (18.4%) children HbA1-values within the normal range (mean + 2 SD) and in 25 (32.9%) children HbA1 values in the range below mean + 3.5 SD. The therapeutic goal near-normal glycaemia with HbA1-values below mean + 3.5 SD and probably no or only a small risk for diabetics to develop late vascular complications could be achieved in 39 (50.1%) diabetic children. Our results are compared with those published in literature and with current therapeutic regimens. PMID- 8464197 TI - [Atopic eczema with generalized lymph node swelling and deficient antibody formation despite repeat vaccination with live vaccines (measles, mumps)- atypical vaccination reaction, vaccination damage or vaccination failure?]. PMID- 8464198 TI - [Modification of pediatric lung function measurement by antibacterial filters]. AB - The risk of cross-infection by contaminated lung function equipment can be reduced by the use of antibacterial filters. These filters, however, should have no significant influence on flow measurements. We investigated the effect of a new filter (Pall PF 30) on lung function measurements in 92 children and adolescents with bronchial asthma and cystic fibrosis. In randomized sequence, flow-volume curves and spirometry were registered in the whole body plethysmograph. Values measured with filter correlated closely to those registered without; individual values remained close to the line of identity. With high flow rates, however, there was a minimal tendency towards lower measurements with filter; this damping effect was flow-dependent and remained of a clinically insignificant dimension. PMID- 8464199 TI - [Correlation between tyndallometry with the "laser flare cell meter" in vivo and biochemical protein determination in human aqueous humor]. AB - INTRODUCTION: The laser flare-cell meter allows noninvasive measurement of aqueous flare in humans. In vitro studies have shown good correlations between flare values and albumin concentrations. In this study, we compared aqueous flare values and aqueous protein concentrations in living human eyes. PATIENTS AND METHODS: We measured aqueous flare and the total aqueous protein concentration in 52 eyes of 52 patients (age 58.4 +/- 18.8 years) that underwent cataract extraction (22 eyes) or trabeculectomy (30 eyes). Before surgery, aqueous flare was determined with the laser flare-cell meter (Kowa FC-1000). During surgery, 50 microliters of primary aqueous humor was aspired, and total aqueous protein concentration was performed using a modified Pierce-BCA assay. Linear regression analysis was calculated. RESULTS: There was a high correlation between aqueous flare values and total aqueous protein concentration (y = 0.52x + 0.15, r = 0.98, p < 0.00001). This correlation was observed both in eyes with and without cataract. CONCLUSION: Our results indicate that aqueous flare values as determined with the laser flare-cell meter reflect the true aqueous protein concentration quite accurately. Lens opacities appear not to significantly alter the results of aqueous flare measurements. As expected by theoretical assumptions, flare measurements overestimate aqueous protein concentrations in eyes with severely impaired blood-aqueous barriers because, according to Rayleigh's law, larger protein molecules cause more light scattering. However, transformation and expression of flare values as "albumin concentration equivalents" according to in vitro-calibration may still be useful, especially if the results of different instruments are to be compared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464200 TI - [Pseudo-accommodation of diffractive multifocal lenses and monofocal lenses]. AB - 35 patients were examined for their pseudoaccommodation 6 to 18 months after cataract extraction and implantation of a diffractive multifocal intraocular lens (MIOL). While in 15 patients a MIOL had been implanted in both eyes 20 patients had a MIOL in one eye only. 45 type 3M 815 LE and 5 3M 825 XE lenses were implanted. The mean age was 58.2 years +/- 9.6 years (33 to 76). Only patients without any pathology except cataract and preoperative refractive errors < +/- 5 diopters of spherical and +/- 1 diopter of astigmatic refraction were eligible for implantation of MIOLs. After estimation of the objective and subjective refraction the patients' pseudoaccommodation was measured by testing their visual acuity, adding lenses of +/- 1, 2, 3, 4, 5 diopters to their best distance correction. All patients with MIOLs reached a visual acuity of 0.4 or better with a maximum peak at 0 and -3 diopters. The visual acuity of the MIOL patients was significantly better in the range of -1 to -4 diopters compared to the results of a control group of patients with monofocal IOLs. This suggests a wider range of pseudoaccommodation in patients with MIOLs. PMID- 8464202 TI - [Tear production in premature infants, newborn infants and infants]. AB - These investigations concerned 50 babies at the age of 34 to 47 weeks and two days. After local instillation of anesthetic drops, Schirmer-1-test was done. The average basal tear production was 5 mm +/- 3 mm in 5 minutes. This result was independent of absolute age of the babies, of birth weight, of the degree of maturity and of sex; there was no significant difference between right or left side. PMID- 8464201 TI - [Principles of measurements in tonometry at the time of Albrecht von Graefes to D2 mission and self-tonometry]. AB - There is no doubt that an elevation of intraocular pressure (IOP) precedes any morphological or functional glaucomatous damage for years, if not decades. Surprisingly, in the present glaucoma literature methods for a quantification of such a damage are prevailing. There might be two reasons for this: The question of tonometry is supposed to be perfectly and definitely solved or tonometry as the most significant diagnostic tool for an early diagnosis of glaucoma has been lost out of sight. Two aspects shall be discussed in the following: Firstly, we want to deal with an improved glaucoma management especially in the early phase of the disease. The question is when and how often should tonometry be performed to detect the typically greater diurnal fluctuations of IOP in glaucoma. This has already been pointed out in particular by Sampaolesi and Hager. Secondly, the technique of the most appropriate tonometer for this purpose is outlined. Important aspects are the accuracy of the instrument according to the standard set by the Goldmann applanatation tonometer as well as safety and easy handling. Like in other branches of medicine where the patient is more and more involved in his own disease control (eg self-measurement of blood pressure in patients with arterial hypertension), self-tonometry is likely to become a revolutionary step towards an improved management and follow-up of glaucoma. These are the objectives we should concentrate on. Technical solutions, clinical applications and experiences are demonstrated. PMID- 8464203 TI - [Clinical electroretinography: standard protocol and normal values]. AB - The International Standard of Clinical Electroretinography serves as standard protocol for recording electroretinographic responses in order to facilitate worldwide comparisons of examinations. To promote its distribution and acceptance throughout the German speaking countries, we established normal values for the five standard responses and added a German translation of the International Standard in the appendix. To determine normal values for electroretinographic data we suggest to use percentiles instead of parameters based on a Gaussian distribution. Patient-related (age, sex) and -unrelated (interstimulus-interval, diurnal rhythm) parameters proved to influence the data values significantly. With these variables taken into account one can increase the clinical value of electroretinography in terms of a greater reliability and predictiveness of data. PMID- 8464204 TI - [Resorbable implant materials in retinal detachment surgery. Initial animal experiment studies]. AB - In detachment surgery after a mechanically stabile chorioretinal scar is at present full scleral indentation no longer mandatory. Following these considerations absorbable scleral implants have been developed and tested in an animal model. Cylindrical pieces of absorbable composite-material with a diameter of 5 mm were sutured as radial scleral explants in 18 rabbits. The composite material consisted of a polyglactin-polydioxanon ratio 7:1. The absorption time for polyglactin is 60 days, for polydioxanon 180 days. The explants produced initially in ultrasonographically measured buckle height between 3.2 and 4.0 mm. The clinical and ultrasonographical follow up study demonstrated a continuous decrease of buckle height. Two weeks after implantation there was a medium height of 2.0 mm after five weeks a medium elevation of 0.5 mm was found. Histopathological examinations showed incidence of a slight resorptive inflammation in the area of the buckle which was not evident after 12 weeks. No scleral infiltration or scleral thinning was found. The promising results have justified controlled clinical trials with the absorbable material which might allow to combine the advantages of silicone sponge explants (precise localization) with those of scleral buckles by inflatible balloons (reversibility). PMID- 8464205 TI - [Properties of injectable intraocular lenses]. AB - An aphakic eye can be corrected by injecting a liquid into the lens capsule following phacoemulsification and hardening the lens by UV irradiation. Another technique is to implant a thin casing of silicone rubber, that is then filled with liquid. The eye's resulting refraction depends strongly on the refractive index of the lens material. In either case, continuous control of the index of refraction is necessary while injecting the artificial lens material. PMID- 8464206 TI - [Effect of pulse duration of the Er:YAG laser on photoablation in ocular tissue (cornea and sclera)]. AB - After photoablation in corneal and scleral tissue with the Er:YAG laser, two zones of thermal damage can be detected: The first zone (about 3 microns thick) consists of thermally denatured debris. The second zone (about 30 microns thick) shows a slightly more intense staining (H&E) compared to the non-influenced tissue. Variation of laser pulse duration between 100 microseconds and 1300 microseconds does not influence the extension of these two thermal damage zones. Furthermore, ablation rate and ablation volume remain nearly constant within this range of pulse durations. These data were obtained by histology (H&E staining) and with a recently published silicon cast replica method. All experiments have been performed on corneas and sclera of pig eyes. PMID- 8464207 TI - [Primary localized amyloidosis of the eyelid and conjunctiva]. AB - Report on a case of amyloidosis in the orbits of a 81-year-old women with 20 year's follow up. At first examination she presented with cystic changes of the palpebral conjunctiva and spontaneous hematoma of the lid. Preceding diagnosis by biopsy six years of unspecific local therapy with various eye drops followed then by cryotherapy and two surgical interventions. Discussion of primary localized amyloidosis and other variants of amyloidosis and therapeutic approach. PMID- 8464208 TI - [A new white-noise campimeter]. AB - In this prototype white-noise field is now generated on a high definition adjustable 19" colour monitor. With the help of a "touch-screen" the patient can draw the borders of his scotoma himself. As the white-noise stimulus is produced by software, there is a much greater variability of white-noise field specifications (brightness, intensity of noise, colour, ...). Furthermore, these parameters can be changed exclusively in circumscribed parts of the noise field (e.g. in a scotoma area). By that way a simulation or even a quantification of perceived noise field defects can be realized. Fixation is controlled with the help of an IR video camera. Input and storage of data as well as their presentation and output (on a Laserwriter) have been substantially improved. PMID- 8464209 TI - [Intraocular inflammation--retrospect of the year 1991]. PMID- 8464210 TI - [Osteoma of the choroid]. PMID- 8464211 TI - [Comments on Kuckelkorn R., Reim M.: On a family with blepharophimosis, ptosis, epicanthus inversus and telecanthus--the occurrence of the hereditary marker in 5 generations]. PMID- 8464212 TI - [Experiences with disc lenses composed of silicone]. AB - Our study presents the results with a silicone disc-lens (Adatomed 90D) over a postoperative period of 18 months. It includes 47 patients, 42 could be reexamined. The implantation was done after continuous circular capsulorhexis and phacoemulsification with a Faulkner-folder directly into the capsular bag. The implantation was sometimes difficult. Skill and experience of the surgeon are required. The IOL springs forth of the implantation forceps, which can lead to traumatization of the capsule and the iris. Three times the posterior capsule ruptured, in two cases the implantation was stopped because of vitreous pressure and the risk of rupturing the capsule. In 6 cases the rim of the anterior capsule ruptured during the implantation. Postoperatively one IOL had a sulcus position, all other IOLs were in the capsular bag. A deposit of viscoelastic substance (Healon) between the IOL and the posterior capsule in 34 cases (72%) was remarkable. In 14 cases (33%) it remained for 18 months. 16 times (38%) regeneratory after-cataract reached the central part of the capsule. The visual disturbance was different, in 6 cases (14%) a YAG-laser-capsulotomy was performed. An influence of the deposit of viscoelastic substance on the development of posterior capsule opacification could not be proved. 17 IOLs (40%) were minimally decentrated upwards. Only 11 cases (26%) had an excellent mydriatic pupillary reaction. The reason is not clear. 10 eyes (24%) developed iridocapsular synechia, 22 eyes (52%) foreign body giant cells and 20 eyes (48%) dispersed pigment on the IOL surface. The giant cells did not diminish.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464213 TI - The construct validity of Templer's death anxiety scale in Filipino students. PMID- 8464214 TI - Sex-related differences in perceptions of sexual harassment of women in India. PMID- 8464215 TI - Self-esteem and specificity in self-focused attention. PMID- 8464216 TI - The relationship between academic self-concept and school withdrawal. PMID- 8464217 TI - Dimensions of interpersonal relation among Australian children and implications for psychological well-being. AB - Three dimensions of interpersonal relations among Australian school children were hypothesized as reflecting tendencies (a) to bully others, (b) to be victimized by others, and (c) to relate to others in a prosocial and cooperative manner. School children from two secondary schools (School A, n = 285; School B, n = 877) answered 20 questions assessing styles of interpersonal relations. Factor analyses of the item scores obtained from each of the two schools provided highly similar results, supporting the factorial independence of the three hypothesized dimensions. Students attending School B answered additional questions to assess self-esteem, level of happiness, and liking for school. Generally low levels of self-esteem were found among children who reported being more victimized than others, and high self-esteem among children practicing more prosocial behavior. The tendency to bully others was correlated negatively with happiness and liking school, but no relationship was found between this variable and self-esteem. PMID- 8464218 TI - Social desirability of personality items as a predictor of endorsement: a cross cultural analysis. AB - Earlier studies using specialized instruments confirmed a positive relation between a personality item's desirability and its endorsement outside North America, but allowed for few conclusions about the strength of the relationship in non-Western societies and offered no explanations for the observed correlations. In Study 1 of this investigation, university students from Turkey (a country rich in non-Western cultural elements) were found to be as likely as their U.S. counterparts to describe themselves in socially desirable terms. Furthermore, the strength of the relationship between desirability and endorsement did not depend on their level of exposure to the English language or to Western concepts. Study 2 indicated that socially desirable traits were also the most common among students in Turkey (paralleling results with U.S. samples), in support of desirable traits' prevalence as an explanation for the desirability endorsement correlation. PMID- 8464219 TI - Effects of cooperative and individualistic learning on prospective elementary teachers' music achievement and attitudes. AB - The effects of cooperative and individualistic learning on the achievement and attitudes of prospective elementary school teachers (non-music majors) in a course in music teaching methods were examined. Forty-three American college students were randomly assigned to conditions stratified on the basis of previous musical experience. Cooperation promoted higher achievement than did individualistic efforts on assignments for which each student's grade was affected by the quality of groupmates' work. In addition, students in the cooperative condition were off-task academically (such as walking around the room) less frequently, initiated fewer interactions with the instructor, perceived the instructor to be more supportive, perceived the grading system to be fairer, and perceived the feedback received as being more helpful. PMID- 8464220 TI - Depressive symptoms among Vietnamese-American college students. AB - Fifty Vietnamese-American college students completed questionnaires measuring depressive symptoms, stressful life events, and acculturation to Vietnamese society versus U.S. society. In contrast to the findings of earlier studies, in which attention was limited to depressive symptoms specific to traditional Vietnamese culture, no gains in reliability or validity were apparent when analyses were limited to these symptoms. Acculturation to U.S. society was positively associated with increased reports of depressive symptoms, as was the occurrence of stressful life events. Implications of these findings are discussed in terms of the changing nature of the Vietnamese-American population. PMID- 8464221 TI - Length-tension characteristics of bovine tracheobronchial lymphatic smooth muscle. AB - Current information regarding the physiology of lymphatic smooth muscle is derived from experiments on mesenteric and thoracic duct lymph trunks. We hypothesized that tracheobronchial lymphatics share many of the same properties possessed by the mesenteric lymphatics, and examined the passive and active length-tension characteristics of the two. Fresh isolated lymph vessel rings were prepared from bovine mesenteric and tracheobronchial lymphatic collectors, mounted in organ baths, and connected to force-displacement transducers. Isometric contractions were induced by exposure to 65mM KCl-substituted perfusate after intermittent ring length changes. Active tension was calculated. Optimal vessel length was greater in tracheobronchial vessel rings, averaging 4.9 +/- 0.4mm vs 2.8 +/- 0.3mm in mesenteric rings (p < 0.001). Optimal resting tension and ATmax were similar for both truncal types, measuring 738 +/- 95mg and 2379 +/ 289mg in tracheobronchial vessel rings, and 625 +/- 108mg and 2501 +/- 320mg in mesenteric vessel rings, respectively. Stress developed at L(o) (optimal length) was similar for tracheobronchial (35.4 +/- 4.3mN mm-2) and mesenteric (26 +/- 4.3mN mm-2) lymphatics (P = N.S.). The data demonstrate that tracheobronchial lymph vessels are similar to mesenteric lymph vessels in their ability to generate significant stress, and suggest that these lymphatics participate in the regulation of lymph flow. PMID- 8464222 TI - Topical treatment of acute hindlimb lymphedema of the rat using a troxerutin phosphatidylcholine complex in liposomal-like microdispersion. AB - A new reversible complex between troxerutin and phosphatidylcholine (85-90mg/kg per day), in the form of a liposome-like water microdispersion, was topically applied to the rat thigh in an experimental counterpart of acute lymphedema. After four days there was 75% less hindlimb edema (mean decrease 40% of normal compared to control 10% of normal) in the treated compared with the untreated rats. These findings suggest that this drug preparation may be useful to minimize acute peripheral lymphedema in patients. PMID- 8464223 TI - The influence of local hyperthermia on lymphedema and lymphedematous skin of the human leg. AB - The influence of microwave and hot water immersion hyperthermia on lymphedema and lymphedematous skin of the leg in 12 patients was studied using circumference and volumetric measurements, immunohistochemistry and "quantitative" lymphoscintigraphy. Whereas heating was associated with a reduction in the girth and volume of the leg, lymph flow as assessed by lymphoscintigraphy was unchanged. Neither absorption of the radiolabeled nanocolloid from the injection site nor the rate of tracer accumulation in the inguinal lymph nodes was significantly altered by heat therapy. Histologically, the lymphedematous skin after heat treatment showed near resolution of perivascular cellular infiltration, disappearance of "lymph lakes" and dilatation of blood capillaries. Labeling of skin migrating immune cells with monoclonal antibodies confirmed subsidence of dermal cellular infiltration; nonetheless, there was nonspecific stimulation of resident epidermal immune cells, endothelial cells, macrophages, lymphocytes and keratinocytes by intense expression of class II and other antigens. There seemed to be a direct relationship between the subsidence of dermal inflammation and a decrease in leg edema. We suspect that subsidence of local inflammation in the lymphedematous limb with alteration in the extracellular protein matrix after regional heating accounts for the reduction in peripheral edema. PMID- 8464224 TI - Lipoperoxide in the dermis of patients with lymph stasis. AB - Lipoperoxide has been detected in the thoracic duct lymph of the dog. This finding suggests that lipoperoxides are normally transported in lymph and with impaired lymph drainage may be deposited in the skin and contribute to the soft tissue changes characteristic of chronic lymphedema. Accordingly, after obtaining skin specimens taken from 8 patients (7 with obstructive lymphedema) with lower extremity lymph stasis we determined dermal malondialdehyde (MDA) content (after conversion to fluorescent thiobarbituric acid or TBA), a marker of lipoperoxide. In all 7 patients with obstructive lymphedema, the MDA levels were increased compared to control dermis (p < 0.05). We suggest that inability to clear lipoperoxides from the dermis with lymphatic insufficiency may contribute to the pathogenesis and structural skin derangements of chronic lymphedema. PMID- 8464225 TI - Regulation of water balance between blood and lymph in the frog, Rana pipiens. AB - To determine the relative importance of the lymphatic system and transcapillary reabsorption in maintaining water distribution between blood and lymph in Rana pipiens, the hematocrit (HCT) was measured (12 frogs) when each frog was: 1) under tricaine methanesulfonate (MS222) anesthesia, which inactivates the lymph hearts, 2) conscious at rest (control), and 3) conscious after activity. Arterial pressure (AP), lymph-heart rate (LHR), and plasma and lymph protein concentrations and colloid osmotic pressures (COP) were also measured. The average HCT during control state was 26.0 +/- 5.2% (SD), AP was 21.9 +/- 5.2 mmHg, and LHR was 86 +/- 13 bpm. MS222 increased HCT (42.6 +/- 7.9%), and did not affect AP. Experiments, in which plasma volumes were determined by intra-arterial injection of Evans blue-labeled albumin (EB-BSA) (16 frogs), showed that the increased HCT reflected a reduced plasma volume. Activity did not affect HCT, but increased AP (33.1 +/- 6.4 mmHg, p < 0.01), and LHR (115 +/- 26 bpm, p < 0.01). Thus lymph hearts are largely responsible for maintaining blood volume, and changes in transcapillary filtration rate are rapidly mirrored by changes in lymph heart function. Plasma and lymph COP values after MS222 or activity were not significantly different from control. This observation is consistent with the protein and fluid fluxes resulting from Starling forces if an average reflection coefficient to protein, sigma, of 0.5 is assumed, which is consistent with our EB BSA data. PMID- 8464226 TI - Scanning electron microscopy of the deep lymphatic network of the murine lung as viewed in corrosion casts. AB - The lymphatic microvessels of the deep lung tissue were studied in corrosion casts, which were observed by scanning electron microscopy (SEM) after injection of a methacrylate resin (Mercox) through the trachea of CD-1 mice. We found that the deep lymphatics of the murine lung were composed of two interconnecting networks: a poorly developed capillary system located at the interacinar region, and a rich plexiform complex surrounding the bronchus. Lymphatic capillaries did not penetrate the alveolar area, thus leaving most of the lung parenchyma devoid of direct access to lymphatic drainage. Lung lymphatic vessels showed a small luminal surface and a low density of endothelial nuclei. Pulmonary lymphatic capillaries often formed star-like anastomoses. The structural features of pulmonary lymphatics, including their three-dimensional organization, were distinctly separate from those of the blood microvasculature of the lung. PMID- 8464227 TI - Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. AB - It is well known that cytogenetic analysis in patients with myelodysplastic syndrome (MDS) provides information useful in determining their prognosis. Based on the chromosomal results obtained from 401 MDS patients by a multicentric study in Japan, we studied correlations between chromosomal findings and prognosis or leukemic transformation in MDS patients. Patients with complex aberrations (cytogenetic abnormalities at more than three chromosomes), of any subtype, had a poor prognosis; for example, > 60% of patients with refractory anemia (RA) showing complex aberrations died within one year, but only 11% of them developed leukemia. In patients with RA with ringed sideroblasts (RARS), > 70% of those with complex aberrations evolved into the leukemic phase and survived for less than one year, suggesting a biologic heterogeneity in RARS patients. By contrast, about 5% of patients with RA or RARS exhibiting chromosomal findings other than 7/7q-, +8, two aberrations, and complex aberrations, developed leukemia and had a favorable prognosis. Therefore, the presence of chromosome abnormalities alone in patients with RA or RARS is not a factor in predicting leukemic transformation or poor prognosis. In patients with refractory anemia with an excess of blasts (RAEB), the presence of chromosome aberrations at MDS diagnosis affected the occurrence of leukemic transformation (24% versus 43%), however, no particular difference was noted in patients with RAEB in transformation with regard to whether they had chromosome changes or not, and about 60% of them evolved into leukemia. The poor prognosis related to complex aberrations was consistently noted in all MDS subtypes or age-matched groups, indicating that this cytogenetic anomaly is an independent risk factor for a poor prognosis in MDS patients. The duration between MDS diagnosis and development of the leukemic phase and that between the latter and death were significantly shorter in patients with complex aberrations than those without this change. Although the clinical significance of certain chromosomal abnormalities differs among subtypes of MDS, a new scoring system for predicting prognosis by cytogenetic changes, in combination with hematologic parameters, was proposed. PMID- 8464228 TI - Multiple chromosome abnormalities in patients with acute leukemia after autologous bone marrow transplantation using total body irradiation and marrow purged with mafosfamide. AB - Cytogenetic follow-up studies such as those reported after allogeneic bone marrow transplantation are not available in patients submitted to an autologous bone marrow transplantation (ABMT). Of 114 patients with acute leukemia (69 acute myelocytic AML, 43 acute lymphocytic ALL, 2 undifferentiated) who underwent an ABMT in our institution in the period from February 1983 to December 1989, 66 had evaluable cytogenetic data post-transplant. They all received a pretransplant regimen consisting of cyclophosphamide (CY) and total body irradiation (TBI) followed by reinfusion of marrow purged with mafosfamide. Twenty patients showed chromosomal damage at some time; of these, six relapsed early post-ABMT, one died while in persisting remission at 81 months post-ABMT from overwhelming pneumococcal sepsis related to a previous splenectomy, and 13 are still alive and well at 13 to 88 months post-transplant. The bone marrow cytogenetic abnormalities were complex: they included various numbers of clonal aberrations or variations or combination of those; they affected all but the Y chromosome, with a predominance however for chromosomes 1, 3, 6, and 7; they were often transitory and in some instances became modified with time. None of these chromosomal abnormalities was connected with the initial leukemia, even in the 6 patients who relapsed early. In the other 14 patients, these abnormalities have so far had no detectable unfavourable implication. The origin of these abnormalities is unknown: both the pretransplant regimen (CY and/or TBI) and/or marrow purging with mafosfamide can be incriminated. Additional studies in patients autografted with pretransplant regimen not containing TBI and/or with unpurged marrow are necessary to discriminate between these two possibilities. PMID- 8464229 TI - Trisomy 12 in chronic lymphoid leukemias--a metaphase and interphase cytogenetic analysis. AB - Trisomy 12 has been shown to be one of the most common chromosome abnormalities in chronic lymphoid leukemias of B-cell origin, and some studies suggested that it predicts poor overall survival. We have prospectively studied 42 patients with B-cell chronic lymphocytic leukemia (B-CLL) and three patients with B prolymphocytic leukemia (B-PLL) for the incidence of trisomy 12 and other chromosome 12 aberrations applying fluorescence in situ hybridization (ISH) and conventional G-banding analysis. Dual-color hybridization experiments using centromere-12-specific DNA probes were performed for interphase cytogenetics. A subset of patients (n = 11) was analyzed using a DNA library for painting of chromosome 12. The incidence of trisomy/partial trisomy 12 was 18% (8/45 patients; 6/42 with B-CLL and 2/3 with B-PLL) by fluorescence ISH, and 11% (5/45 patients; 4/42 with B-CLL including one patient with partial trisomy 12q13-qter, and 1/3 with B-PLL) on G-banding analysis. Four patients with trisomy 12 were detected by ISH alone. One of these patients only had 4.5% interphase cells with three fluorescence signals indicating the presence of a small subclone with trisomy 12. On G-banding analysis, three of the four patients had a normal karyotype, and one patient had no analyzable metaphases. In conclusion, fluorescence ISH to interphase nuclei is a sensitive method for detecting trisomy 12 in patients with chronic lymphoid leukemias. PMID- 8464230 TI - Translocation t(6;9)(p23;q34) in acute myeloid leukemia without myelodysplasia or basophilia: two cases and a review of the literature. AB - The clinical, hematological, and cytogenetic data from two young adults with acute myeloid leukemia (AML) FAB type M1 is described. At diagnosis, cytogenetic investigation revealed the presence of the translocation t(6;9)(p23;q34). Bone marrow basophilia was not detected in either patient nor was there any evidence of preceding or underlying myelodysplasia. Both patients achieved complete remission (CR) and one patient remains in CR of over 5 years duration. It is suggested that the presence of basophilia may be associated with the myelodysplasia rather than the chromosome anomaly t(6;9). PMID- 8464231 TI - Early diagnosis of smoldering acute lymphoblastic leukemia using immunological marker analysis. AB - During a period of 9 years, we performed immunological marker analysis in 164 children with acute lymphoblastic leukemia. In four children the diagnosis acute leukemia could not be established by cytomorphological analysis of bone marrow and peripheral blood samples at initial presentation. In two of these four children a hypoplastic bone marrow was found, whereas the bone marrow of the other two children was normocellular. Using double immunological marker analysis, we detected high frequencies of CD10+, TdT+ cells in bone marrow (range: 18-53%) as well as peripheral blood (range: 0.04-19.5%). In control bone marrow and peripheral blood samples from healthy children, the frequency of CD10+, TdT+ cells does not exceed 10% and 0.03%, respectively. Based on the immunological data, a common acute lymphoblastic leukemia (ALL) was suspected. In addition, chromosome analysis revealed a high hyperdiploid (> 50 chromosomes) karyotype in three patients and t(9;22) in one patient. At 18 to 68 days after initial presentation, an ALL was diagnosed according to cytomorphological criteria in all four patients. At that time the percentage of CD10+, TdT+ cells in bone marrow and peripheral blood had increased significantly. One patient could be monitored frequently from initial presentation onwards. First a decline in the percentage of CD10+, TdT+ cells was found, although treatment consisted only of red blood cell transfusion and antibiotics. Subsequently the percentage of CD10+, TdT+ cells gradually increased until the morphological ALL diagnosis. These results illustrate that CD10, TdT double immunological marker analysis is a useful tool for early diagnosis of smoldering ALL in patients with a suspicious bone marrow, even when the bone marrow is hypoplastic. PMID- 8464232 TI - Interphase in situ hybridization reveals minimal residual disease in early remission and return of the diagnostic clone in karyotypically normal relapse of acute lymphoblastic leukemia. AB - Early clinical remission of acute lymphoblastic leukemia (ALL) was examined by fluorescence in situ hybridization (FISH) in bone marrow cells from eight patients with high hyperdiploid (> 50 chromosomes) clones at diagnosis. Alphoid centromeric probes to chromosomes X, 10, 17, and 18, trisomic at diagnosis, were used as appropriate. Three hematologically normal marrows were used as controls. At diagnosis, trisomic interphase cells ranged from 69.3-84.4%. One month later, trisomic and tetrasomic interphase cells were significantly increased over control frequencies in 2/7 cases tested (p < 0.05 and p < 0.001) and trisomy alone in one case (p < 0.05). At two months post-diagnosis, trisomy and tetrasomy were in the control range. Pentasomy and hexasomy, not seen in controls, were found in 5/7 samples at one month and in 1/5 samples at two months. One patient examined in chromosomally normal relapse had 34.4% trisomic cells by FISH at confirmed relapse (p < 0.001). An additional hyperdiploid case, examined at central nervous system relapse, had increased numbers of trisomic cells (p < 0.01) in a morphologically and cytogenetically normal marrow. These findings demonstrate the elimination of aberrant ploidy in most hyperdiploid cases two months from diagnosis and indicate that failure to detect the abnormal clone in relapse may result from selective mitotic activity of chromosomally normal cells, rather than relapse in a cytogenetically normal clone. PMID- 8464233 TI - Mitoxantrone, etoposide and intermediate-dose Ara-C (MEC): an effective regimen for poor risk acute myeloid leukemia. AB - A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or documented infections in almost 100% of patient; major hemorrhagic complications occurred in 39% of patients. Extrahematologic toxicity was mild to moderate consisting mostly of nausea and vomiting, oral mucositis and transient liver and cardiac dysfunction. We conclude that the MEC combination chemotherapy program seems to be an effective antileukemic regimen for secondary and advanced AML, with acceptable toxicity. PMID- 8464234 TI - Cytotoxic activities of recombinant immunotoxins composed of Pseudomonas toxin or diphtheria toxin toward lymphocytes from patients with adult T-cell leukemia. AB - We have previously shown that the recombinant single-chain immunotoxin anti Tac(Fv)-PE40, composed of the variable domains of the anti-Tac monoclonal antibody in a single-chain form joined to a derivative of Pseudomonas exotoxin (PE), is cytotoxic toward malignant cells from adult T-cell leukemia (ATL) patients. Using this assay, we have now compared the activity of anti-Tac(Fv) PE40 with that of an improved version, anti-Tac(Fv)-PE40KDEL which contains an altered carboxyl terminus, and also with two chimeric toxins made with diphtheria toxin (DT). One of these is a fusion of amino acids 1-388 of DT with anti-Tac(Fv) and is termed DT388-anti-Tac(Fv). The other, DT388-IL2, contains interleukin 2 (IL2) at the carboxyl terminus of the same DT derivative. We incubated these toxins with malignant ATL peripheral blood mononuclear cells (PBMCs) for 1-3 days and then measured [3H]leucine incorporation. We found that anti-Tac(Fv)-PE40KDEL was the most cytotoxic agent and was followed in decreasing order of activity by anti-Tac(Fv)-PE40, DT388-anti-Tac(Fv), and finally DT388-IL2. Trypan blue staining showed that inhibition of protein synthesis correlated with cell death. Time course studies showed that the recombinant toxins containing anti-Tac(Fv) were cytotoxic even if exposed to the cells for only one hour. After intravenous injection into mice, the half-life of anti-Tac(Fv)-PE40 or anti-Tac(Fv)-PE40KDEL was 30 minutes. Normal PBMCs were resistant to all four toxins. Recombinant immunotoxins made with anti-Tac merit further study as potential reagents in the treatment of ATL. PMID- 8464235 TI - Quantitative analysis of the expression and regulation of an activation-regulated phosphoprotein (oncoprotein 18) in normal and neoplastic cells. AB - Activation of protein kinase C results in phosphorylation of a 19-kDa protein termed 19K. Isolation and sequence analysis of a cDNA encoding the 19K protein revealed that this protein has been studied in other systems under different names. The name oncoprotein 18 (Op18) has been proposed on the basis of a postulated up-regulation in neoplastic cells. In the present report we adopt the designation Op18 for the 19K protein, and quantify this phosphoprotein in a series of leukemia/lymphoma cell lines, a panel of non-transformed cells and some terminally differentiated cell types. For this purpose we have developed reagents allowing quantitative Western-blot analysis, and quantification of Op18 on the single cell level by flow cytometric analysis. The data demonstrates a pronounced up-regulation of the Op18 protein in most leukemia/lymphoma cell lines. The HPB ALL cell line provided the most extreme case and expressed 7 x 10(6) Op18 molecules/cell, which compares with 0.65 x 10(6) Op18 molecules/cell in non transformed lymphoblastoid cells. The expression of Op18 appears to be restricted to cell types with proliferative potential, but it is clear from our results that up-regulation of Op18 is uncoupled from cellular proliferation. Moreover, by employing an Epstein-Barr virus based shuttle vector, we expressed Op18 cDNA in lymphoblastoid cells. This resulted in a three to fourfold up-regulation of Op18 that did not have any detectable consequences for cell-surface phenotype or cell size. However, increased expression of Op18 resulted in a partial inhibition of cell proliferation. Taken altogether, the results suggest that up-regulation Op18 levels in leukemia/lymphoma cells are strongly associated with, but not a direct cause of tumour progression. PMID- 8464236 TI - Molecular analysis of the LMP (latent membrane protein) oncogene in Hodgkin's disease. AB - Molecular analysis of the LMP (latent membrane protein) oncogene was performed in 21 Epstein-Barr virus (EBV) positive cases of Hodgkin's disease (HD) with proven LMP gene expression. In each case, viral DNA of the LMP gene was assessed for polymorphism (deletions, insertions, mutations) by polymerase chain reaction (PCR) amplification with selected primers. Specificity of the amplified targets was proven by internal oligonucleotide hybridisation and nested primer PCR. Homogeneity of the 5' LMP gene region coding for the amino terminal, transmembrane, and short extracytoplasmic domains of the protein was identified in all cases. However, deletions or insertions of small DNA sequences within the coding region for the intracytoplasmic LMP domain were observed in about 20% of cases. In one of them, a 30-base-pair deletion was precisely localized by DNA sequencing. A particularly high frequency of DNA polymorphism (30% of cases) was found in the 3' untranslated LMP region. However, when analysing the LMP gene in seven benign conditions, no DNA polymorphism was found. These data suggest conservation of oncogenic LMP regions coding for the protein domains known to be associated with transforming capacities and immunogenic functions. They also show a considerable genomic heterogeneity of the coding region for the intracytoplasmic domain and the 3' untranslated mRNA region. This LMP DNA polymorphism identified within a localized (Swiss) population suffering from HD is unexpected. Its eventual clinical significance remains to be determined. PMID- 8464237 TI - Molecular diversification of dominant subclones in vivo and in vitro in Ph positive ALL. AB - A leukemia line KOPN30bi was established from a patient with acute lymphocytic leukemia (ALL) and Philadelphia (Ph) chromosome. The clonal rearrangement of the immunoglobulin heavy chain (IgH) gene and the expression of the P190 type BCR/ABL chimeric transcript were shown to be identical between KOPN30bi and the predominant clone (S1) in the blast cell population from which KOPN30bi was established, indicating that they are of the same clonal origin. Studies of the T cell antigen receptor (TCR) gene configuration including the TCR beta, gamma, and delta loci showed that none of them was identical between KOPN30bi and S1. The TCR delta region was rearranged on both of the alleles in KOPN30bi and was deleted on both alleles in S1 indicating that KOPN30bi was not derived from S1. Polymerase chain reaction analysis, using an oligonucleotide probe corresponding to the N region sequence of the V gamma-J gamma juncture of KOPN30bi, indicated that only 0.1% of the blast cells corresponded to KOPN30bi. Thus molecular diversification of dominant subclones in vivo and in vitro was shown in Ph positive ALL. PMID- 8464238 TI - Genetic alterations in the p53 gene in the blast crisis of chronic myelogenous leukemia: analysis by polymerase chain reaction based techniques. AB - Rearrangements of the c-abl protooncogene and the bcr-gene are found in > 90% of patients in chronic phase of chronic myelogenous leukemia (CML). The molecular events leading to blast crisis, however, have not been well characterized. Gross alterations of the p53 gene have been detected in 30% of patients with blast crisis. Since point mutations in the p53 gene appear to be important in the process of transformation in many epithelial tumors, we looked for these mutations in the critical regions of the p53 gene (exons 4, 5, 6, 7, and 8). We used the polymerase chain reaction (PCR), direct sequencing, differential PCR, and single strand conformation polymorphism (SSCP) analysis to detect mutations of the p53 gene in samples from 21 patients with CML blast crisis. Two of 21 patients exhibited an intragenic deletion or rearrangement in p53. In addition, these patients were homozygous for the mutant p53 allele. No mutations were found in the p53 gene of the remaining 19 patients. However, sequencing of the CML blast crisis cell line, K562, revealed an insertion of a C at base position 956 within the fifth exon, causing a frame shift mutation and an early translational stop at codon 148. We conclude that, in contrast to solid tumors, mutations in exons 4-8 of p53 are not frequently seen in primary samples from CML blast crisis. However, deletions and/or rearrangements within the p53 gene do occur and may contribute to the progression from chronic phase to blast crisis in a limited number of patients with CML. PMID- 8464239 TI - Effect of IL-4 and IL-6 on the proliferation and differentiation of B-chronic lymphocytic leukemia cells. AB - The proliferation and differentiation of purified malignant B cells from nine patients with chronic lymphocytic leukemia (B-CLL) were studied in vitro. We have demonstrated before that tumour necrosis factor alpha (TNF-alpha), in combination with low dose phorbol myristic acid (PMA) (0.1 ng/ml), can induce proliferation in these purified B-cell populations and that this TNF-alpha-induced proliferation is completely inhibited by the addition of interleukin 4 (IL-4). In this study we demonstrate that IL-6 is also able to inhibit this TNF-alpha induced proliferation. Inhibition is maximal with 400 pg/ml of IL-6. With the use of neutralizing antibodies we show that the inhibition by IL-4 and IL-6 are independent processes. In contrast, investigation of differentiation as measured by immunoglobulin M (IgM) production, showed that in combination with PMA (1 ng/ml), IL-4 is the main cytokine to induce differentiation of these B-CLL cells. That we were indeed measuring differentiation of the malignant B cells could be demonstrated by the specific production of IgM/kappa or IgM/lambda. No induction of IgG or IgE production could be detected. In contrast to IL-4, in the majority of cases IL-6 does not play a role in the induction of differentiation of B-CLL cells. However, in two out of nine B-CLL patients we found that at low PMA concentrations (0.1 ng/ml), TNF-alpha can induce both proliferation and differentiation. In agreement with what was found for the proliferative response, this TNF-alpha-induced IgM production is inhibited both by IL-4 and IL-6. The possible therapeutic implications of our findings are briefly discussed. PMID- 8464240 TI - LIF mRNA expression is transcriptionally regulated in murine bone marrow stromal cells. AB - Recent evidence has established an important role for leukemia inhibitory factor (LIF) as hematopoietically active cytokine. The present study utilized two different murine bone marrow stromal cell lines, +/+-1.LDA11 and MBA-13, to define regulatory mechanisms of LIF messenger RNA (mRNA) induction. LIF mRNA was not detected in uninduced stromal cells under serum-free conditions. Incubation with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha) or the cAMP analogue 8-bromoadenosine 3':5'-monophosphate (8BrcAMP) resulted in weakly induced LIF mRNA. Coincubation of combinations of the stimuli increased LIF mRNA expression additively. LIF mRNA stability, even after stimulation, was low with a half-life of about 30 min, suggesting a functional role for known AU-rich motifs in the 3' untranslated LIF mRNA region in mediating this instability. This possibility was further supported by the ability of cycloheximide to increase mRNA levels without affecting transcription. Transcriptional activation was found to be the main mechanism leading to LIF mRNA expression by IL-1, by TNF-alpha, and by 8BrcAMP. These stimuli appeared to act additively in this regard, suggesting involvement of distinct transcription factors. Induction of transcription was detected 45 min post-stimulation and showed peak levels at 90 min. Kinetics of LIF transcriptional activation showed similarity with the kinetics of the transcription factors, jun-B and c-fos, suggesting a possible role for these proteins or other early response genes in events leading to LIF expression. PMID- 8464241 TI - Characterization of a t(1;19) pre-B acute lymphoblastic leukemia (ALL) cell line which proliferates in response to IL-7. AB - The present study describes the establishment of the cell line Pre-Alp from the bone marrow of a pediatric patient with a t(1;19) pre-B acute lymphoblastic leukemia (ALL) at diagnosis. Proliferation of leukemic blasts was found to be initially dependent on the presence of autologous stromal cells. However, after five weeks of culture, the stromal cells were no longer necessary and cells began to grow autonomously, with a doubling time of approximately 24 hours. The established Pre-Alp cell line displays a pre-B cell phenotype (CD19+, CD10+, CD34 , c mu+, s mu-), with immunoglobulin (Ig) light chain DNA in germline configuration, and carries a (1;19)(p23;q13.3) chromosomal translocation identical to the freshly-isolated leukemic blasts. A unique feature of this cell line is represented by its ability to respond to interleukin 7 (IL-7). Thus, IL-7 enhances 3H-thymidine uptake by Pre-Alp cells in a dose-dependent manner, under conditions of low cell density and serum concentration, and increases cell recovery. Finally, Pre-Alp cells were found to remain at a pre-B stage even upon addition of various cytokines, which failed to induce a transition to surface Ig+ cells. The presently described cell line should constitute a useful model of t(1;19) pre-B ALL and permit the study of IL-7 dependent signal transduction in human pre-B cells. PMID- 8464242 TI - Inhibitory effect of interleukin-4 on the proliferation of acute myeloid leukemia cells with myelo-monocytic differentiation (AML-M4/M5); the role of interleukin 6. AB - Since interleukin-4 (IL-4) specifically inhibits monocytic colony formation in human bone marrow cultures, we investigated whether a similar inhibition could be observed in cultures of optimally stimulated acute myeloid leukemia cells with myelomonocytic differentiation (AML-M4/M5). Sensitivity to IL-4 was tested in 19 cases of AML-M4/M5, using both a 3H-thymidine incorporation assay and a clonogenic assay. Proliferation was stimulated with a combination of IL-3, granulocyte-monocyte colony-stimulating factor (GM-CSF), and conditioned medium from phytohemagglutinin-stimulated leukocytes (PHA-CM). In 13 out of 14 evaluable cases, IL-4 inhibited 3H-thymidine incorporation; stimulation was seen in one case. Using a clonogenic assay, IL-4 inhibited colony formation in all evaluable cases (n = 7). Addition of IL-6 did not alter the observed inhibition by IL-4 in 9 out of 10 cases tested. We conclude that IL-4 inhibits the proliferation of optimally stimulated AML-M4/M5 cells in most cases tested, and that this effect is not generally caused by inhibition of autocrine IL-6 production. PMID- 8464243 TI - Combined immunophenotyping and interphase cytogenetics on cryostat sections by the new FICTION method. AB - A technique is described to detect tumor cells with certain chromosome aberrations within cryostat sections and to characterize these individual cells by immunophenotyping. This new method is called fluorescence-immunophenotyping and interphase cytogenetics as a tool for investigation of neoplasms (FICTION). PMID- 8464244 TI - Myelodysplastic disorders with hemizygous M-CSF receptor gene loss do not show point mutations of codon 969 within the remaining allele. PMID- 8464245 TI - Chronic myelogenous leukemia: biology and therapy. AB - There is remarkable recent progress in our understanding of the biology of chronic myelogenous leukemia (CML). First, the BCR/ABL rearrangement was identified as the molecular basis of the disease. Second, animal models support the notion that the BCR/ABL gene product causes a syndrome similar to CML. Third, recent advances in understanding the functions of the normal ABL protein have given clues to the mechanism(s) of ABL-induced leukemias and approaches to blocking this process. Extrapolating these findings to humans seems reasonable. The challenge now is to determine how the BCR/ABL gene product causes chronic phase CML. Also unresolved is whether BCR/ABL also plays a role in the acute phase of the disease. Finally, the relationship between the two common forms of BCR/ABL, the P190 and P210 configurations, and different disease phenotypes, like CML and Philadelphia (Ph1)-chromosome positive acute lymphoblastic leukemia (ALL), needs to be clarified. There is also substantial progress in treating CML. Bone marrow transplants have emerged as the preferred therapy. These result in long-term leukemia-free survival in more than one-half of appropriately selected subjects. How transplants cure CML is complex and controversial. Some data suggest high-dose treatment is the dominant factor whereas other data implicate antileukemia effects of the immune system. Interferon treatment has also proven effective in CML. Whether it prolongs survival of persons with CML remains to be determined, as does its mechanism of action. Certainly the most important and difficult challenge in CML therapy is determining how to use knowledge about the causes CML to treat the disease. These and other issues in the biology and therapy of CML were the subject of a recent meeting of basic and clinical scientists. The meeting, third in a series begun in 1987, was held on Martha's Vineyard, Cape Cod, Massachusetts, USA from 4-7 April, 1992. Four major topics were considered in five sessions: molecular biology, cell biology, Ph1-chromosome positive ALL, and therapy of CML. This report summarizes meeting highlights. PMID- 8464246 TI - Physician frustration in communicating with patients. AB - In this study, the nature of practicing physicians' "frustrating" visits was explored and a guide to help physicians identify problems in communicating with patients was developed. The study included 1,076 practicing physicians who attended a voluntary workshop on physician-patient communication. The physicians were from multiple specialties and diverse work settings geographically dispersed throughout the United States. The method included development of a preliminary item pool (descriptions of frustrating patients and occasions) by experienced physicians and teachers of medical communication, additions/deletions/revisions of items within the pool, empirical analyses to reduce redundancy and group-like items, and construct validation of the final 25-item questionnaire. Factor analysis was used to identify subscales. Physicians most often attributed communication problems to the patient rather than to their own limitations. Seven types of communication problems (subscales) were identified, including: 1) lack of trust/agreement, 2) too many problems, 3) feeling distressed, 4) lack of understanding, 5) lack of adherence, 6) demanding/controlling patient, and 7) special problems. Primary care physicians reported greater problems than specialists on four subscales. Physicians practicing in health maintenance organizations reported greater problems than physicians in fee-for-service practice on five subscales. Seven sources of frustration physicians experience in their work with patients were identified. Understanding these frustrations will allow physicians to reflect on their own experiences and potentially improve the quality of their patient visits. PMID- 8464247 TI - Medicare prospective payment reforms and hospital utilization. Temporary or lasting effects? AB - Early evaluations of the Medicare prospective payment reforms found them very effective in reducing hospital utilization. In this study, the author investigated whether the reforms remained effective throughout the first decade of implementation. Seasonal autoregressive-integrated-moving average (ARIMA) models with intervention components were applied to age-specific national times series of hospital admissions, average length of stay, inpatient days, and adjusted inpatient days. Three alternative regulatory impact patterns were tested using quarterly data collected by the National Hospital Panel Survey spanning the period 1970:1 to 1992:1 (n = 89). The reimbursement reforms seem to have reduced hospital admissions, average length of stay and patient days during fiscal years 1983-1984, but significant readjustments relative to projected levels occurred for all four utilization measures during fiscal years 1985-1986. Similar, yet less pronounced readjustments, were found in the analysis of non-Medicare time series suggesting regulatory spill-over effects. Sicker patients and hospital diversification efforts are two plausible reasons for the relative increase in hospital utilization during 1985-1986. The Medicare reimbursement reforms appear to remain effective in reducing hospital utilization, but at a reduced rate. PMID- 8464248 TI - A preliminary case-mix classification system for Medicare home health clients. AB - In this study, a hierarchical case-mix model was developed for grouping Medicare home health beneficiaries homogeneously, based on the allowed charges for their home care. Based on information from a two-page form from 2,830 clients from ten states and using the classification and regression trees method, a four-component model was developed that yielded 11 case-mix groups and explained 22% of the variance for the test sample of 1,929 clients. The four components are rehabilitation, special care, skilled-nurse monitoring, and paralysis; each are categorized as present or absent. The range of mean-allowed charges for the 11 groups in the total sample was $473 to $2,562 with a mean of $847. Of the six groups with mean charges above $1,000, none exceeded 5.2% of clients; thus, the high-cost groups are relatively rare. PMID- 8464250 TI - Main trends in hospital use in different cities in Japan. AB - In this study, trends in hospital use were identified in Japanese cities. Data for all inpatient care in May 1985 (9,555 patients) and in May 1988 (11,205 patients) paid for by National Health Insurance in 12 cities in Osaka Prefecture were analyzed. The main factor affecting differences in inpatient days per insured person of all ages (hospital use) among the cities were differences in hospital use by long-stay patients aged 70 years or older, which depended not on inpatient days per patient but on the rate of hospital admission. The main factor affecting change in mean hospital use from May 1985 to May 1988 seemed to be an increase in hospital use by long-stay patients 70 years of age or older, which did not depend on increases in the rate of hospital admission, but did depend on the number of insured persons 70 years of age or older. Calculation showed that an increase of 13 long-stay patients 70 years of age or older for 10,000 insured persons 70 years of age or older per year was to have accounted for about 40% of the increase in hospital use by all patients. If the trend for increasing hospital use in Japan is to be altered, the first step might be the careful planning for this comparatively small increase in long-stay elderly patients by promotion of a non-hospital-based care system. PMID- 8464249 TI - Patterns of use of mammography among inner-city Detroit women: contrasts between a health department, HMO, and private hospital. AB - This study assessed the pattern of utilization of mammography among 2,880 inner city minority women 40 years of age or older who received ongoing primary care services during 1988 or 1989 at four practice sites operated by a health department (two sites), Health Maintenance Organization (HMO), and private hospital. Mammography referral could be documented for 23% to 32% of age eligible women and completed mammograms for 15% to 26%. Among women without a mammogram, 85% had never been referred while 15% were referred but unable to complete the procedure. In multiple logistic regression analysis, factors associated with mammography include age less than 70 years, presence of a breast cancer risk factor and more frequent clinic visits. Mammography was somewhat more frequent at the HMO and hospital clinic than at the health department, but this relationship varied with the women's previous visit and mammography experience. At sites serving uninsured women, mammography use was not associated with the presence or absence of health insurance. It is concluded that the underutilization of mammography is a substantial barrier to the early detection of breast cancer in each of the three different health care organizations studied, and that interventions to improve breast cancer control should focus upon facilitating physician referral practices. PMID- 8464251 TI - Functional status outcomes in rehabilitation. Implications for prospective payment. AB - Previous studies have demonstrated that functional status is a significant predictor of resource utilization for rehabilitation patients. Before implementing a prospective payment system (PPS) for rehabilitation, it is important to first: 1) develop an underlying conceptual framework of rehabilitation resource use; and 2) understand how the role of functional status may vary by rehabilitation condition. In this study, a theoretical model of rehabilitation is presented that proposes relationships between patient and provider characteristics, rehabilitation treatment, costs, and clinical outcomes of rehabilitation. Also presented are regression analyses based on this model for a key outcome of rehabilitation, change in functional status, for nine rehabilitation conditions using variables that minimize adverse incentives by providers in selecting patients for admission to rehabilitation. The change-in functional-status model explained the most variance for back injury, cardiopulmonary, and arthritis, and less variance for stroke, spinal cord injury, and neurologic impairment. The significant predictors of change in functional status varied by condition. Results support the use of functional status measurements in a PPS for rehabilitation services, the need to refine the measurement of functional status, and the use of condition-specific activities of daily living (ADL) items to include in summary indices. PMID- 8464252 TI - Evaluating hospital discharge planning: a randomized clinical trial. AB - To select patients for early discharge planning, a randomized clinical trial evaluated a protocol that used risk factors identified upon hospital admission. The goal of the study was to determine if intervention with high-risk patients could reduce the need for hospital admission or skilled care. Of 13,255 patients screened, 835 study participants were identified as "at risk" for frequent health care resource use. Half of the high-risk patients were randomly assigned to the experimental group (n = 417) and received discharge planning from day 3 of their hospital stay, while the control group (n = 418) received discharge planning only if there was a written physician request. Those patients receiving early, systematic discharge planning experienced an increased likelihood of successful return to home after hospital admission and a decreased chance of unscheduled readmission for the 9-month study period. Length of the index hospital stay was not affected by early planning, however. The major clinical implication is the potential for discharge planners to decrease the need for, and use of, health care resources after hospital admission. PMID- 8464253 TI - Differences in length of hospital stay in patients with community-acquired pneumonia: a prospective four-hospital study. PMID- 8464254 TI - [The coronary sulcus and ischemic cardiopathy: an independent association of risk factors]. AB - BACKGROUND: Coronary sulcus of the auricular lobe has been related to the presence of ischemic cardiopathy although the nature of this relation has not been well defined. The aim of the present study was to determine whether there is a relation between the sulcus and the classical coronary risk factors, or whether the association between coronariopathy and sulcus is independent of such factors. METHODS: Patients admitted into an intensive care unit (n = 222) were divided into two groups according to whether coronary sulcus was present and the following analysis were performed: 1) comparative study between the groups for the variables: age, sex, coronariopathy, hyperglycemia, hyperlipidemia, hypertension, index of body mass, and tobacco habit. 2) logistic regression analysis used as a variable to study the existence of coronary sulcus and as independent factors the different coronary risk factors. 3) calculation of sensitivity and specificity of the coronary sulcus as a marker of ischemic cardiopathy. RESULTS: In the comparison between groups the individuals with coronary sulcus had greater age, cholesterolemia, index of body mass, with greater frequency found in females with ischemic cardiopathy. In the logistic regression analysis the presence of coronary sulcus was only associated by order of statistical significance to the variables of age and the female sex. In this study, coronary sulcus was a sensitive (87.6%) although unspecific (41.2%) marker of coronariopathy. CONCLUSIONS: The prevalence of coronary sulcus increases with age, and is greater in patients with ischemic cardiopathy. This relation is independent of the classical coronary risk factors. PMID- 8464255 TI - [The use of antibiotics in surgical prophylaxis. The characteristics and consequences]. AB - BACKGROUND: The efficacy of antibiotic prophylaxis in certain surgical procedures has been demonstrated in clinical trials. The present study aimed at getting knowledge on the way how it is used in a certain hospital. METHODS: In a certain day, all patients receiving antibiotics to prevent a postoperative infection were identified in a medical school hospital. Information on the operative procedure, prescribed antibiotics and clinical course of the patients was recorded. RESULTS: Out of 714 patients admitted, 255 (36%) were treated with antibiotics and, of these, 85 were given them to prevent a postoperative infection. In 52% of patients, two or more antibiotics were given. The mean (SD) duration of prophylaxis was 8.4 (8.6) days. It was judged as really indicated in 34 cases (40%). Only in 17 (20%) the first choice antibiotic was selected; in 11 (13%) a preoperative dose of the right antibiotic was administered and only in 3 (3.5%) a preoperative dose of the first choice antibiotic was administered and prophylaxis lasted up to 48 hours. CONCLUSIONS: The use of antibiotics in surgical prophylaxis in a medical school hospital is inappropriate in more than 95% of cases. The situation in other centres should be quantified and the universally accepted norms of prophylaxis should be implemented. PMID- 8464256 TI - [Inadequate hospital admissions and inactive days of hospital stay in patients with chronic obstructive pulmonary disease and lung neoplasms]. AB - BACKGROUND: This study was carried out to evaluate the hypothesis that the proportion of inadequate hospital admissions and days is greater in patients with pulmonary neoplasm than in patients with chronic obstructive pulmonary disease (COPD) given the therapeutic and diagnostic features of both diseases and to establish the applicability of the Appropriateness Evaluation Protocol (AEP). METHODS: A retrospective review was performed of the medical records of patients admitted for COPD and pulmonary neoplasm. Two external physicians reviewed the clinical histories using the AEP. Admissions and hospital days considered as potentially inadequate by the reviewers were supervised by a clinical epidemiological panel which confirmed and identified the causes for inadequacy. One hundred sixty-six patients admitted with COPD and 79 with pulmonary neoplasm selected by a systematic sample of admissions whose principal diagnosis was COPD or pulmonary neoplasm were studied over one year in a tertiary level teaching hospital in Barcelona. RESULTS: It was found that 4.8% of the admissions with COPD and 15.5% of the days of hospital stay were inappropriate while in patients with pulmonary neoplasm 14% of the admissions and 40% of the days of hospital stay were inappropriate. The main causes of inadequacy were: social (33.3% in patients with COPD); patients inadequately admitted but who remained in hospital to undergo diagnostic tests which could have been performed on an out patients basis (46% in patients with pulmonary neoplasm). CONCLUSIONS: Inappropriateness was greater in admissions and in hospital days with greater diagnostic components (pulmonary neoplasm) than in fundamentally therapeutic cases (COPD). The Appropriateness Evaluation Protocol was valid in this hospital with the supervising panel being very useful in the judgement of cases not clearly established in the protocol. The level of inadequacy was found to be similar to that of other studies although the results are not directly comparable. PMID- 8464257 TI - [Dopamine and dobutamine in shock: together or separately?]. PMID- 8464258 TI - [Hospitalization at home in the rural environment]. PMID- 8464259 TI - [Bacteremia and multiple and recurrent skin ulcers due to Brucella melitensis. A new modality of self-induced infection]. AB - Self-induced infections are a special form of factitious disease. They are characterized by the autoinoculation of contaminated substances or bacterial cultures which may lead to cutaneous infections, bacteremias, or arthritis by various germs. The conditions produced are difficult to diagnose and may lead to multiple operations, and sometimes mutilations or death of the patient. Herewith, a patient who, over a period of 10 months, presented 4 episodes of bacteremia and cutaneous abscess in which Brucella melitensis was isolated is described. In addition, during the second admission, the patient had factitious fever. Despite the evidence of self induced infection, the patient denied autoinoculation however, following confrontation with the facts and supportive psychotherapy the patient has not presented any further episodes after 6 months of follow up. Although the microorganisms involved in this type of disorders are various, this is the first case described in the literature of self-induced infections by Brucella melitensis. PMID- 8464260 TI - [The inappropriate antidiuretic hormone secretion syndrome associated with cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome]. AB - Meningitis and other infectious diseases of the central nervous system are predisposing causes of the inadequate secretion syndrome of the antidiuretic hormone (ISADH). The association between the acquired immunodeficiency syndrome (AIDS) and ISADH is recognized but little studied. In AIDS patients hyponatremia is a frequent finding and it is responsible for ISADH in most cases. However, there is little reference material concerning the incidence of presentation and the type of osmoregulation anomaly this entity presents in these patients. A case in which ISADH is associated to cryptococcal meningitis and AIDS is described with an evaluation of the hormonal response to the test of hypertonic saline serum infusion corresponding to a release of ADH. PMID- 8464261 TI - [Good clinical practice in clinical trials: the responsibilities of the investigator. A survey of 827 hospital physicians (and II). Patient consent]. AB - BACKGROUND: Among the responsibilities of the investigator, good clinical practice (GCP) includes that of obtaining informed consent (IC) from the patients prior to his/her inclusion into a clinical trial (CT). The attitude of the hospital physicians towards this question before the implementation of the GCP became mandatory in Spain was considered to be of interest. METHODS: An anonymous survey with closed response questions was used. From December 1988 to February 1990 the survey was distributed among 1,706 hospital medical staff members of any specialty who had or had not participated in CT. The results of the questions regarding different aspects intimately linked to the obtaining of the IC from the patient are presented in this article. RESULTS: A total of 827 hospital doctors responded to the survey. Most (96%) of those surveyed considered that the investigator must obtain the IC prior to inclusion in the CT with almost two thirds obtaining the same in writing in all CT. Nine out ten of those surveyed considered that the information provided to the patient to obtain the IC should be laid out in a document. At least 90% of the above consider that the document should always invite the patient to participate in a CT, declaring that participation is voluntary, that the patient may leave the study when he/she wishes and that refusing to participate does not imply loss of normal health care. To the contrary, at least 10% would not provide information as to who the promoter was, the design of the CT, specific experimental procedures of the CT as the number of patients to participate in the CT. CONCLUSIONS: According to the good clinical practice guidelines, the responsibilities of the researcher with respect to informed consent of patients to participate in a clinical trial have, in general, been accepted by most of the hospital physicians surveyed in the present study. Theoretically, only the reduced acceptance of informing the patient as to the design of the clinical trial may cause some problems in the future. PMID- 8464262 TI - [Amino-terminal procollagen type-III peptide and hepatic fibrogenesis]. PMID- 8464263 TI - [Kaposi's sarcoma with pulmonary involvement in a heterosexual man seronegative for the human immunodeficiency virus]. PMID- 8464264 TI - [Dysphagia as the presentation of amiodarone-induced hyperthyroidism]. PMID- 8464265 TI - [Legionellosis with a splenic granulomatous reaction]. PMID- 8464266 TI - [Gastric carcinoma secondary to an autologous bone marrow transplant. Apropos a case with a possible relationship]. PMID- 8464267 TI - [Plasma fibronectin concentrations in critical patients]. PMID- 8464268 TI - [The sicca syndrome and human immunodeficiency virus infection]. PMID- 8464269 TI - [Health inequalities in Barcelona and Valencia]. AB - BACKGROUND: Inequalities in health have been internationally recognized as an important public health problem with a reduction of 25% being the first target of WHO--Europe for the year 2000. It is, therefore, important to describe and monitor the same. METHODS: An ecological study was performed using secondary data from the statistics of mortality (years 1985-1988) and the municipal censuses from the year 1986 to describe and compare inequalities in health in the cities of Valencia and Barcelona with neighborhoods being the unit of observation and analysis. RESULTS: Although the rates of mortality in Barcelona city are slightly inferior and those of Valencia slightly higher to those of Spain, both cities demonstrate important inequalities in regard to mortality in their neighborhoods with respect to standardized mortality which ranged from 78 to 182 in Barcelona and from 63 to 147 in Valencia. The privileged zones in Barcelona are those of Pedralbes and Sant Gervasi and in Valencia in the neighborhoods of Sant Pau and Jaume Roig with the most unfavorable neighborhoods being District I in Barcelona (Gothic Quarter, City Park, Barceloneta and Raval) and the Na Rovella and Fuensanta neighborhoods of Valencia. The level of inequality in both cities is very similar. Statistically significant associations have been found in both cities between the state of health and the level of poverty in the neighborhoods according to an approximation to the Townsend et al indexes. CONCLUSIONS: The description of important inequalities in two large Spanish cities suggests the possibility of its existence in other cities and established the urgent need for a study using comparable methodologies. With the use of routine and presently available data sources it is possible to describe and posteriorly monitor the level of inequality in large cities in Spain. The development of policies to diminish the inequalities in the large cities would provide considerable gains in terms of human lives. The present results support the hypothesis that material conditions in everyday life play an important role as a condition for public health inequality. PMID- 8464270 TI - [Sleep apnea in arterial hypertension]. AB - BACKGROUND: The sleep apnea syndrome (SAS) and high blood pressure (HBP) present multiple relations. Apnea culminates with an increase in arterial pressure, and a high percentage of apneic patients have HBP. It has also been reported that SAS is more frequent among hypertensive patients than among the general population. METHODS: In the present study 91 essential hypertensive individuals were studied by a questionnaire and polygraphic study of night sleep, to establish the prevalence of SAS among hypertensive subjects and the predictive value of the clinical questionnaire. RESULTS: The prevalence of SAS in HBP was 8.8%. The greatest predictive value was found for the presence of respiratory pauses every night and throughout the night. The risk factor of greatest association was cigarette smoking and the greatest organic repercussion was observed in renal function. CONCLUSIONS: An increase in the prevalence of sleep apnea syndrome was found among essential hypertensive subjects, thus leading this syndrome to be suggested as a risk factor of high blood pressure. The question as to whether the patients present daily pauses between snores and throughout the entire night is suggestive and implies confirmation by polygraphic study of night sleep. PMID- 8464271 TI - [Neurosarcoidosis: presentation of 14 cases]. AB - BACKGROUND: The involvement of the nervous system in sarcoidosis occurs with a frequency of approximately 5%. The aim of this study was to review the frequency and characteristics of the neurologic manifestations of the a series of sarcoidosis. METHODS: During a period of 18 years (1974-1991) 270 patients were diagnosed with sarcoidosis in the Hospital de Bellvitge-Princeps d'Espanya. The diagnosis of neurosarcoidosis was performed in those presenting neurologic symptoms no attributable to other causes. The clinical histories were retrospectively reviewed collecting clinical, radiologic, analytic, therapeutic and evolutive data. RESULTS: Fourteen patients (5.1%) were diagnosed of neurosarcoidosis. Neurologic symptomatology was the first manifestation of the disease in 12 (85%). All showed extra-neurologic manifestations of sarcoidosis with the lung being the most frequently affected organ (78%). The clinical picture consisted of cranial neuropathy in 11 cases of which nine presented peripheral facial paralysis and 4 cases involvement of the central nervous system. In 13 patients the treatment schedule included glucocorticoids. All the patients (100%) with alteration of the central nervous system continued with active disease at 2 years while this only occurred in 33% of the cases with paralysis of the cranial pairs. CONCLUSIONS: The frequency of neurosarcoidosis in the authors' series was similar to that described in the literature and its most frequent clinical form was cranial neuropathy. The treatment of choice was glucocorticoid and the involvement of the cranial pairs presents a better prognosis than that of the central nervous system. PMID- 8464272 TI - [Health and social inequality]. PMID- 8464273 TI - [Proteinuria as cardiovascular and renal risk factor]. PMID- 8464274 TI - [Factitious torpid skin ulcers. New concepts and classification of chronic factitious disorders]. AB - Chronic factitious disorders are diseases diagnosed after the discarding of organic causes. There are determined diagnostic data which may be suspicious: multiple hospitalization, submission to many invasive techniques and personal situations motivating simulation. The case of a 34 year old woman presenting a factitious disorder with dermal ulcers, subcutaneous abscesses and simulation of hematuria is described. An analysis of the concept and classification of this clinical picture is made. Following diagnostic suspicion, a search for objects or substances with which the patient was able to make the lesions was required to determine the appropriate therapy. PMID- 8464275 TI - [Septic shock (II). Treatment]. PMID- 8464276 TI - [Anaphylactic reaction caused by vitamin B1]. PMID- 8464277 TI - [Bacteroides fragilis meningitis complicated with thrombosis of the lateral sinus]. PMID- 8464279 TI - [Endometriosis with urinary involvement associated with hepatic hemangioma]. PMID- 8464278 TI - [Menopause and substitutive hormonal therapy]. PMID- 8464281 TI - [Unforeseen shortages in market economy. Are there alternatives to the buy-sell system in health care?]. PMID- 8464282 TI - [Let "Svensson" decide about his health care. Insurance instead of power of politicians]. PMID- 8464280 TI - [Prevalence of serum markers of hepatitis B virus in patients hospitalized with pelvic inflammatory disease]. PMID- 8464283 TI - [In the head of a general practitioner]. PMID- 8464284 TI - [Buy and sell and emperor's new clothes]. PMID- 8464285 TI - [Who has a bad back?]. PMID- 8464286 TI - [Brain clinics are needed]. PMID- 8464287 TI - [Nicotine supplementation to pregnant women, in spite of all]. PMID- 8464288 TI - [Is the specialty of pediatric surgery overdimensioned?]. PMID- 8464289 TI - [Significant bacteriuria--where should the line be drawn?]. PMID- 8464290 TI - [The sociopsychiatric view is emphasized]. PMID- 8464291 TI - [Quantitative measurement of atherosclerosis. Development of ultrasound techniques is worth while]. PMID- 8464292 TI - [Reduced postoperative pain. Epidural infusion of bupivacaine in the ward]. PMID- 8464293 TI - [Annual statistics of the Central Board of Animal Experiments: most increasing is the use of birds and swine as experimental animals]. PMID- 8464294 TI - [Colitis--a partial phenomenon in adult Still disease?]. PMID- 8464295 TI - [The man behind the syndrome: George F. Still. The first professor of pediatrics]. PMID- 8464296 TI - [More and more children are stricken by asthma. Modern flats are the most usual breeding ground. Interview by Birgit Wilhelmson]. PMID- 8464297 TI - [Diaphragmatic rupture caused ileus]. PMID- 8464298 TI - [An atypical case of Kawasaki disease]. PMID- 8464299 TI - [Johan von Hoorn. Father of Swedish obstetrics]. PMID- 8464300 TI - [No to euthanasia and living wills. Patient's current wishes serve as guidance]. PMID- 8464301 TI - Cisplatin-induced ototoxicity: the effect of pigmentation and inhibitory agents. AB - Cis-diamminedichloroplatinum II (cisplatin), a divalent platinum compound and potent cell-cycle nonspecific chemotherapeutic agent, produces a dose-limiting, permanent, high-frequency sensori-neural hearing loss and peripheral neuropathy, and a dose-related cumulative renal insufficiency with tubular necrosis and interstitial nephritis. The potential for dose-limiting and permanent cochlear (neuro) toxicity remains despite present methods of hypertonic saline, prehydration, and mannitol diuresis prior to drug administration. The exact mechanism(s) of ototoxicity and/or nephrotoxicity are still unknown. Continued aggressive high-dose cisplatin chemotherapy necessitates the investigation of ways to decrease the dose-limiting side effects that inhibit the administration of cisplatin at therapeutic and tumoricidal doses. This multifaceted project investigates two categories of potential inhibitors of cisplatin toxicity that, when coadministered with a known tumoricidal and ototoxic dose of cisplatin, will decrease or inhibit the ototoxicity: 1. phosphonic acid antibiotics (fosfomycin; 1,2 epoxypropylphosphonic acid); 2. nonglucocorticoid 21-aminosteroids, which are free oxygen radical scavengers (LAZAROIDS: U74006F and U78517F). This project also investigates the role of pigmentation as a variable affecting the evaluation of platinum-induced ototoxicity in the guinea pig animal model. Identification of an optimal animal model for future cisplatin toxicity research should be based on previously established species-specific differences in total drug dose, systemic toxicity, and morphological and functional evidence of cochlear toxicity, as affected by differences in pigmentation and drug tolerance. Cytocochleography, brainstem auditory evoked response (BSER), scanning and transmission electron microscopy of organ of Corti and the stria vascularis, double-blind light microscopy of renal, small intestine, and peripheral nerve tissue, and gamma emission analysis of 195Mplatinum localization in inner ear neuroepithelium and the stria vascularis are used in the global evaluation of the ototoxic effects of cisplatin in both the adult albino and pigmented guinea pig. PMID- 8464302 TI - XeCl laser ablation of atherosclerotic aorta: luminescence spectroscopy of ablation products. AB - XeCl laser ablation of atherosclerotic aorta tissue was investigated. Luminescence spectra of ablation products were measured for soft and hard arterial tissues. A pronounced difference observed between plume luminescence for various plaques and normal vessel wall correlates with the chemical composition of the tissue. The mechanism of plume luminescence appeared to be thermochemical excitation ablation products (particles, atoms, molecules, etc.) in the air. The process of soft tissue ablation was delayed with respect to the exciting laser pulse at relatively low laser fluences close to the ablation threshold. The kinetics of the ablation process as a function of laser-pulse energy fluence is reported. The data indicate that tissue ejection mechanism, which involves vapor bubbles formation, expansion and explosion, is suitable for the description of the XeCl excimer laser ablation of soft tissues. PMID- 8464303 TI - Noncontact determination of skin blood flow using the laser speckle method: application to patients with peripheral arterial occlusive disease (PAOD) and to type-I diabetics. AB - The laser speckle method allows the noncontact determination of skin blood flow and its dynamics from a distance of 5 cm. The method is based on the time dependency of the speckle pattern formed by the scattered light of a 5 mW He-Ne laser (632.8 nm). Utilizing the speckle intensity measured through a pinhole, an electronic circuit generates an output signal denoted as blood flow parameter B. All measurements were carried out on the foot dorsum during steady-state, ischemia, and reactive hyperemia induced by a 3-min arterial occlusion. The investigations were carried out in four groups: healthy subjects, asymptomatic smokers, PAOD-patients, and type-I diabetics (D) with severe late complications. As shown by parallel measurements with the tcpO2-method, the initial value Binit of the blood flow parameter B indicates the steady-state blood flow. Binit decreases significantly from 5.95 +/- 2.55 (S.D.) for the control to 4.07 +/- 1.69 (PAOD) and 3.81 +/- 1.51 (D). The half-time BTrh for the increase of B at the beginning of the reactive hyperemia is significantly increased from 4.10 +/- 2.06 s (control) to 14.5 +/- 15.4 s (smokers), 17.6 +/- 32.7 s (PAOD), and 5.31 +/- 3.55 s (D). Other characteristic values such as peak value and time of peak during the reactive hyperemia as well as the final steady-state value and the time of its achievement exhibit similar effects. The correlation coefficients between the different characteristic values obtained from the laser speckle method indicate that the characteristic times of the dynamics and the absolute values of B vary separately and provide supplemental information. A two dimensional representation of the characteristic values facilitates the differentiation between the four measured groups. PMID- 8464304 TI - Improved excimer laser photorefractive keratectomy system. AB - An improved 193 nm excimer laser photorefractive keratectomy system is described here. The delivery system was optimised to produce a smooth keratectomy bed, to minimise the healing response, and to reduce the regression of the refractive result. A spatial filtering system was used to smooth the energy distribution within each pulse, and the iris was adjusted for every pulse, to eliminate steps and other irregularities from the keratectomy profile. An image rotator was used to average out any remaining non-uniformities in the energy distribution. The results from the first 39 eyes treated with this laser system with a maximum follow-up of 18 months, are summarised. No epithelial healing problems were noticed, and little or no loss of corneal clarity was noted at any stage during healing. Twenty of the keratectomy procedures were normally sighted myopic corrections, with a maximum follow-up of 5 months. Minimal regression of the refractive correction was seen during the first 8 weeks. PMID- 8464305 TI - Effectiveness of corneal neovascularization photothrombosis using phthalocyanine and a diode laser (675 nm). AB - We used chloroaluminum sulfonated phthalocyanine as a photo-sensitizer and a diode laser as a light source for induction of photothrombosis of corneal neovascularization. Corneal neovascularization was induced in 1 eye of each of 10 New Zealand white rabbits using intrastromal 6.0 silk sutures. After the intravenous injection of phthalocyanine in a dose of 4 mg per kg of body weight, photothrombosis was carried out using a diode laser emitting at 675 nm. The animals were followed up by both fluorescein angiography and slit-lamp photography for up to three months. At the end of the follow-up period the eyes were prepared for histology. After photothrombosis, thrombus formation was induced within new vessels demonstrating histological characteristics of both arterioles and venules. Most of the vessels disappeared or remained closed during the follow-up period. Recanalization of some of the thrombosed vessels occurred within the first 20 days after the operation. The combination of phthalocyanine and a 675 nm diode laser is effective for the induction of photothrombosis of corneal neovascularization. PMID- 8464306 TI - Transmission of corneal collagen during ArF excimer laser ablation. AB - The time-resolved transmission of collagen films and 10-microns sections of bovine cornea during ArF laser ablation has been investigated. The film studies were performed on thin layers of extracted bovine corneal collagen, the principal chromophore in 193 nm photoablation. Transmission measurements were made on both dry and water-saturated films to assess the sensitivity of the ablation process to hydration. Distinct transient optical changes were observed in both fully desiccated and rehydrated films. Dehydrated films exhibit rapid reduction in film absorption over the time-course of the ablating laser pulse, presumably due to chromophore bleaching or annihilation. In contrast, rehydrated films demonstrate a short-lived enhancement of the attenuation. In either case, a single ablative laser pulse increased the long-term transmission of the film, although this increase was a factor of five greater for dehydrated films than for rehydrated samples. Results obtained from corneal tissue sections were essentially identical to those derived from hydrated collagen films. PMID- 8464307 TI - Preliminary experience with transluminal laser-induced intrahepatic portacaval shunts. AB - This study investigated the feasibility of performing an intrahepatic portacaval shunt (IHPCS) by means of transluminal laser angioplasty. In 10 anesthized dogs, a catheter was introduced into a mesenteric vein and threaded into the portal vein (PV). Under fluoroscopy, a Ross needle was passed through the PV catheter, liver, and into the intrahepatic IVC. Following guidewire exchange, a neodymium YAG laser hot-tip probe (power setting 8 W) was passed over the guidewire to accomplish a transluminal IHPCS. In five animals, an IHPCS could not be accomplished. Initial and subsequent patency was confirmed by fluoroscopy. These early data suggest that transvenous laser-induced intrahepatic portacaval shunts may be feasible as a means of decompressing portal hypertension. Further research is necessary, to investigate the long-term patency as well as this technique's ability to decompress the portal system. PMID- 8464308 TI - Modeling the color perception of port wine stains and its relation to the depth of laser coagulated blood vessels. AB - To find the maximal depth of an ecstatic vessel in the dermis that contributes to the abnormal color of a port wine stain (PWS), "normal" and "laser treated PWS skin" are modeled, respectively, as a two-layer plane parallel geometry consisting of an epidermis and a dermis, and as a three-layer geometry consisting of an epidermis, a dermis without additional blood (the "treated" part of the stain, assumed identical to the "normal" dermis), and a layer of dermis containing 5% or 10% of blood per volume (the untreated part of the PWS). Spectral remittances were calculated for various wavelengths using the diffusion approximation to the transport equation for light propagation. These remittances were transformed into the CIE 1976 (L*a*b*)-color system. Color differences between "normal" and PWS skin as a function of the dermal depth of "injured" ecstatic blood vessels were calculated. The maximal depth where ecstatic blood vessels just contribute to the abnormal PWS color is predicted as 0.9 mm for a "normally" pigmented epidermis (60 microns thick) and a 5% or 10% blood per volume content. For a darker pigmented epidermis (60 microns thickness) and again at both 5% and 10% blood per volume content, this depth was found to be 0.8 mm. PMID- 8464309 TI - 600 nm flash pumped dye laser for fragile telangiectasia of the elderly. AB - Since 1984, a continuum of controlled studies have been done on the use of the fragile, superficial telangiectasia of the elderly, which were utilized as a model for some of the basic studies of the effects of lasers on the cardiovascular system. We report the use of the 600 nm flash pumped dye laser for the fragile telangiectasia of the elderly in our classification of the Class 2 group. In some vessels studied, the special Teflon-insulated, intravenous electric needle of Kobayashi-Yamada was used. For the bluish vessels, the 600 nm flash pumped dye laser penetrated deeper into the vessel than the 585 nm, but multiple and repeated treatments were needed for clinical effect. Preliminary studies have also shown some initial response in port wine marks and facial telangiectasia. PMID- 8464310 TI - Fine structure of zonal changes in experimental Nd:YAG laser-induced interstitial hyperthermia. AB - Interstitial thermotherapy using Nd:YAG-laser induced hyperthermia is a new stereotactic method for the treatment of brain tumors in poorly accessible regions. To provide a basis for the underlying tissue alterations, we have analyzed the spatial and temporal pattern of interstitial laser hyperthermia lesions in the normal rat brain by histological, immunohistochemical, and electron microscopical methods. The acute changes corresponded to the temperature gradient surrounding the laser probe and showed a distinct zonal architecture. Membrane destruction on a cellular and subcellular level appears to be of major significance in the pathogenesis of the laser lesion. The tissue reaction followed the course known for coagulation necrosis and resulted in a well-defined defect. These results, although limited by the choice of the experimental model, may be helpful in the interpretation of images obtained in future applications of interstitial thermotherapy. PMID- 8464311 TI - Effects of plume produced by the Nd:YAG laser and electrocautery on the respiratory system. AB - Sprague-Dawley rats were exposed to Nd:YAG laser exhaust (contact and noncontact) as well as to electrocautery exhaust passed through smoke evacuation filters. Exposure periods for each group were equal and increasing in time. Histologic analysis revealed alveolar congestion and emphysematous changes in all modes. Controls exhibited similar change but to a milder degree. It appears that any plume produced by lasers or electrosurgical devices produces pathologic change in rat lungs and that effective smoke evacuation will help control these effects. PMID- 8464312 TI - Laser vaporization of Peyronie's plaques. AB - A series of four cases of surgical excision or vaporization of Peyronie's plaques using the Neodynium/Yag laser is presented. This technique would appear to decrease the need for grafting procedures with minimal blood loss. It results in straight erections without shortening the penis. PMID- 8464313 TI - Immunopathology of nerve involvement in leprosy. PMID- 8464314 TI - Long-term active surveillance of leprosy suspects--what are the likely returns? AB - Data are presented from the Karonga District in Northern Malawi on the long-term follow up of 277 leprosy suspects who were not given antileprosy treatment or kept on active surveillance. Individuals who were started on antileprosy treatment within a year after leprosy was first suspected, usually on the basis of histopathology results, are excluded from this analysis, because their active surveillance would not usually cause an organizational or financial problem for leprosy control projects. After an average follow-up period of 4.5 years 35 of the 277 suspects included in the analysis (13%) were diagnosed with what we consider to be 'unequivocal' leprosy, and 3 of the 35 had developed disabilities. In 211/277 (76%) all signs of leprosy had disappeared completely. Comparing clinical certainties at first and last examinations and comparing clinical with histopathological certainties at last examinations it is estimated that up to 50% of the 35 cases of unequivocal leprosy which 'arose' in this group were attributable to misdiagnosis at the 1st or 2nd examination rather than to genuine progression of the disease. This estimate is compatible with an overall sensitivity of 90% and an overall specificity of 95% at each examination. Leprosy suspects with 1 cardinal sign of leprosy, either a typical lesion without loss of sensation, or loss of sensation in an otherwise untypical lesion, should be considered a high-risk group in that approximately 25% of such suspects (19/78) were later found with unequivocal leprosy. Policies towards such suspects should be formulated by leprosy control projects. PMID- 8464315 TI - Oral manifestations of leprosy. AB - A total of 37 out of 187 patients with leprosy had oral lesions. All were biopsied. Oral lesions were found most frequently in patients with lepromatous leprosy. Prevalence of oral lesions was higher in males than in females (73%:27%). Oral lesions were recorded on the WHO topographical map, and in most cases (92%) several topographical locations were affected, including hard palate in all cases. Topographical locations affected increase with age; males are more extensively affected than females (p = 0.001); and patients with oral lesions who reported affected family members (11 out of 37) had more extensive oral lesions than those who did not. In 27 cases with oral lesions histopathological diagnosis was possible. PMID- 8464316 TI - A histological study of the eye lesions in 12 leprosy patients with tuberculoid lesion in 4 eyes. AB - The histological reactions in 12 eyes of 12 leprosy patients were studied (5 BT, 1 BB, 1 BL and 5 LL). Granuloma lesions composed of epithelioid cells, Langerhans giant cells, macrophages and lymphocytes were found in various intraocular tissues, e.g. cornea, sclera, iris, ciliary body or retina in 4 patients (1 BT and 3 LL). Of the 3 LL patients, according to the records, 2 were cured and in the other patient the outcome of the treatment was not mentioned. In view of the finding of the granulomatous lesions in the clinically cured patients and tuberculoid granuloma in the intraocular tissues in the LL patients, could there be some peculiarities in the intraocular sites? Or perhaps the tuberculoid reaction is just a manifestation of an upgrading reaction? More examinations on human leprosy eye specimens will be needed to answer these questions. PMID- 8464317 TI - Distinguishing post-kala-azar dermal leishmaniasis from leprosy: experience in the Sudan. AB - In this study 4 patients were post-kala-azar dermal leishmaniasis (PKDL), whose lesions were similar to those of lepromatous and borderline leprosy, are described. In 2 patients there was no previous history of kala-azar but they were residents of an area of known endemic kala-azar. Lack of proper clinical and laboratory assessment was behind the failure to diagnose PKDL. Consequently the patients were treated with antileprosy drugs without proof of leprosy. The 3rd and 4th patients, though suspected clinically of leprosy, were correctly diagnosed as PKDL with adequate history, clinical assessment and appropriate laboratory investigations. The salient points in distinguishing PKDL from leprosy are described and discussed. PMID- 8464318 TI - Paralysis of occipitofrontalis in a borderline case of leprosy. AB - A patient with neuritic leprosy developed borderline skin lesions. Later, another skin lesion developed on the left side of the forehead with clinical involvement of the supraorbital branch of the ophthalmic division of the trigeminal nerve. Simultaneously, paralysis of the occipitofrontalis and mild paresis of orbicularis oculi occurred. PMID- 8464319 TI - Leprosy--the challenge. PMID- 8464320 TI - Immunotherapy with Mycobacterium w vaccine decreases the incidence and severity of type 2 (ENL) reactions. AB - Immunotherapy with Mycobacterium w (M.w) vaccine was given to 45 patients with multibacillary (MB) leprosy; 41 similarly classified patients served as controls. All patients received standard multidrug therapy (MDT). Incidence, severity and frequency of type 2 (ENL) reactional episodes were monitored in both groups in a follow-up extending up to 4 years. Reactions were seen in fewer vaccinated (10/37) BL and LL patients than in the control group (12/34). A total of 20 episodes were recorded in the vaccine group as against 29 in the controls, 75% of reactions were mild in vaccinated and 51.72% were mild in the control group patients, and 3 patients in the control group had more than 3 reactional episodes. None of the vaccinated patients showed this. No additional incidence of neuritis were seen among vaccinated individuals during reactional episodes. PMID- 8464321 TI - A case report: dual mycobacterial infections in a Paraguayan patient due to Mycobacterium leprae and Mycobacterium fortuitum. PMID- 8464322 TI - Considerations in the integration of eye care into leprosy care services. PMID- 8464323 TI - Cor pulmonale subacute and recurrent erythema nodosum leprosum. PMID- 8464324 TI - Time course and magnitude of tolerance to the analgesic effects of systemic morphine in amphibians. AB - The systemic administration of morphine (100 nmol/g, s.c.) produced a significant and long-lasting analgesia (up to 8 h) in the Northern grass frog, Rana pipiens. Daily bolus injections of the same dose of morphine or saline for one week resulted in a significant analgesia for 3 days in the morphine group, which fell to levels indistinguishable from the saline-treated controls on days 4 through 7. In separate experiments, animals were treated identically with morphine or saline but were not tested daily for pain thresholds. In these animals, administration of a range of morphine doses on day 8 yielded dose-response curves significantly shifted rightward by a factor of 3.3 in the morphine-treated group compared to the saline-injected controls. These studies are the first to show the time course of tolerance development and the magnitude of morphine tolerance in a non mammalian vertebrate species. PMID- 8464325 TI - Acetaldehyde-collagen adducts in N-nitrosodimethylamine-induced liver cirrhosis in rats. AB - Increased acetaldehyde levels have been found in non-alcoholic liver diseases and an acetaldehyde-collagen adduct has been reported in rats with CCl4-induced cirrhosis. In cytosol and microsomes of rats with cirrhosis produced by N nitrosodimethylamine, a similar acetaldehyde-protein adduct of approximately 200 kD was recognized by rabbit IgG raised against either an in vitro produced hemocyanin-acetaldehyde adduct or an in vivo occurring P4502E1-acetaldehyde adduct isolated from alcohol-fed rats, as well as by anti-rat collagen (I) IgG. Its immune complexes contained 3 proteins that reacted with the anti-collagen IgG and were digested by collagenase: 2 proteins with molecular weights similar to procollagens alpha 1 and alpha 2, and a beta 1,2(I)-like protein which was readily produced by in vitro modification of cytosol with acetaldehyde. PMID- 8464326 TI - Effects of verapamil on the acquisition of ethanol tolerance. AB - This study investigated the effects of verapamil on the acquisition of tolerance to the ataxic effects of ethanol. Four groups of rats (n = 20/group) were randomly assigned to oral treatment regimes. One group received chronic ethanol treatment (starting at 5 gm/kg/day and increasing by 1 gm/kg at weekly intervals to an eventual dose of 9 gm/kg/day). A second group received the same dose of chronic ethanol together with verapamil (10 mg/kg twice daily). A third group received the same dose of chronic verapamil while the fourth group received chronic placebo treatment. Every fourth day all rats received at least a 2 gm/kg ip test dose of ethanol. Following this, change in motor coordination was measured on an accelerating Rota-Rod treadmill. After six weeks the chronic ethanol group developed tolerance to the test dose of ethanol, while the ethanol and verapamil group did not. Blood ethanol concentrations were not different between the groups. The chronic verapamil and placebo groups developed sensitization to the effects of ethanol but were not different from each other. Chronic treatment with verapamil appeared to delay the acquisition of chronic tolerance to ethanol. PMID- 8464327 TI - Effects of the opioid antagonist naltrexone-estrone azine on the luteinizing hormone-releasing hormone induced release of luteinizing hormone from the pituitary glands of ovariectomized rats. AB - The effects were studied of in vivo administration of the new opioid antagonist estrogen hybrid, naltrexone-estrone azine (EH-NX), on subsequent luteinizing hormone-releasing hormone (LHRH)-stimulated luteinizing hormone (LH) release by the pituitary gland in vitro. It is well known that administration of estrogen exerts negative and positive effects on the pituitary LH response to LHRH, respectively after short-term and long-term treatment. Rats were injected subcutaneously with either 17 beta-estradiol-3-benzoate (EB), EH-NX or oil on days 18 and 19 (long-term treatment), and on day 21 (short-term treatment) following ovariectomy. Twenty minutes later the animals were killed and the pituitary glands were incubated in the presence of LHRH (1000 ng/ml) for 4 h. Whereas short-term treatment with EB on day 21 did not affect LH release in vitro, EH-NX significantly decreased the pituitary LH response to LHRH in oil pretreated rats. This inhibitory effect was partially blocked by the opioid antagonist naltrexone. After long-term EB or EH-NX, followed by short-term oil treatment, the pituitary LH response to LHRH was increased considerably, compared to the long-term oil controls. These observations demonstrate that the opioid antagonist estrogen hybrid EH-NX has estrogenic activity at the level of the pituitary gland. This hybridized drug is more effective in time than EB and an equimolar amount of EH (estrone hydrazone) to induce the negative estrogenic effect. PMID- 8464328 TI - Ethanol modulation of tumor necrosis factor and gamma interferon production by murine splenocytes and macrophages. AB - C57BL/6 female mice were fed a liquid ethanol (ETOH) diet (27% of calories derived from ETOH) for 5 months as an animal model of chronic alcohol use. A isocaloric liquid diet supplemented with maltose dextran was fed to controls. Splenocytes from ETOH-treated and control mice, and purified macrophages from normal mice and retrovirus infected mice were exposed in vitro to various concentrations of ETOH (0.1-1.0% v/v). The effect of chronic ETOH exposure in vivo, and of in vitro treatment with ETOH on tumor necrosis factor (TNF) and gamma-interferon (IFN) production by cultured murine splenocytes and purified macrophages was investigated. Dietary ethanol did not significantly affect in vitro TNF or IFN production. However, TNF and IFN production by splenocytes from mice fed either the ETOH or control diet decreased significantly when the cells were cultured with ETOH and stimulated with LPS or Con A in vitro. Thus ETOH in vitro directly down regulates TNF and IFN secretion by LPS- or Con A-stimulated spleen cells. ETOH treatment in vitro did not significantly change TNF production by purified peritoneal macrophage (PM) and thioglycollate-induced peritoneal macrophage (TPM) from normal mice, but increased TNF production by alveolar macrophage (AM). Although murine retrovirus infection per se increased TNF production it did not change the responsive pattern in TNF production of PM and TPM to ETOH in vitro and reduced the TNF production of AM. PMID- 8464329 TI - Endogenous morphine and codeine: release by the chromaffin cells of the eel. AB - Both the adrenomedullary equivalent and the plasma of the American eel (Anguilla rostrata) contain endogenous morphine and codeine. The opiate concentrations are similar to those found in the rat adrenal and human plasma, respectively. The adrenal medulla equivalent of the eel was perifused in vitro and the levels of catecholamines and endogenous opiate alkaloids in the perfusate were measured. A strong correlation between the release of morphine and codeine and between the release of norepinephrine (NE) and epinephrine (E) was found. On the other hand, there was no significant correlation between the release of dopamine (DA) and that of the other catecholamines or opiate alkaloids, suggesting three different ways of release of these components of the secretory cocktail of the chromaffin cells. The plasma of eels stressed by urethane anesthesia showed a substantial increase in DA, NE, and E levels but there was no clear stress response of plasma morphine and codeine. PMID- 8464330 TI - Distribution of low Km GTPase activity in mouse CNS: effect of chronic morphine. AB - The low Km GTPase displayed an apparent Km value of 0.2-0.4 microM in P2 fractions from whole mouse brain. The activity of this enzyme ranged from 102 (pmols of GTP hydrolysed per micrograms of protein per min) in the striatum to 39 in the pons-medulla oblongata. Intermediate values were found in other structures, 74-62 in thalamus, hypothalamus, periaqueductal gray matter (PAG), rest of mesencephalon, cortex and spinal cord. The Km also varied throughout the mouse CNS: the spinal cord, striatum and PAG exhibited Km values (0.308-0.271 microM) higher than cortex, thalamus, pons-medulla, hypothalamus and remaining mesencephalon (0.239-0.193 microM). Chronic morphine (3 days) decreased the low Km GTPase activity of PAG (42), whereas it increased the one of thalamus (99). After chronic exposure to the opioid the Km values of the enzyme in striatum (0.193), PAG (0.192) and spinal cord (0.201) diminished, and the ones of hypothalamus (0.357) and rest of mesencephalon (0.287) augmented. The herein reported diversity of low GTPase activity might be due to the presence of different ratios of G alpha types/subtypes in the neural structures studied. As a result of chronic morphine the ratio and/or the functionality of G proteins would be altered in particular areas of mouse CNS. PMID- 8464331 TI - Withdrawal from chronic haloperidol substitutes for the pentylenetetrazol discriminative stimulus. AB - The present study was designed to examine withdrawal from a therapeutic, non abused drug, haloperidol. Rats were trained to discriminate the anxiogenic compound pentylenetetrazol (PTZ) from water in a two lever, food reinforced, drug discrimination procedure. Dose effect curves were then determined for PTZ and the antipsychotic drug, haloperidol (0.1-1 mg/kg). Haloperidol did not substitute for PTZ, even at a dose that decreased rates of responding to approximately 15% of control values. Rats were then treated chronically with either 1 or 2 mg/kg/day haloperidol while training was suspended. After 5 days of chronic haloperidol 4/6 animals in the 1 mg/kg/day group and 5/7 in the 2 mg/kg/day group chose the PTZ lever when tested 24-48 hours after the last haloperidol injection. Haloperidol, 1 or 2 mg/kg, did not reverse PTZ-lever responding. After an additional 5 days of chronic haloperidol, 3/6 rats in the 1 mg/kg/day group and 5/7 rats in the 2 mg/kg/day group responded on the PTZ lever 24 hours after the last injection, and this was reversed with the anxiolytic, chlordiazepoxide (3.2-5.6 mg/kg). The current findings indicate that there is an anxiogenic component to withdrawal from haloperidol. In psychotic patients, abrupt discontinuation of haloperidol results in nausea, vomiting and sweating, as well as a "relapse into psychosis" characterized by anxiety, depression and internal chaos (1). Interestingly, the authors caution that the so-called relapse into psychosis may simply be a sign of withdrawal. The current findings support their view and suggest that abrupt discontinuation of psychoactive therapeutic agents may result in anxiety. PMID- 8464332 TI - The cocaine analog WIN 35,428 binds to two sites in fresh rat caudate-putamen: significance of assay procedures. AB - Binding of the potent cocaine analog [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta (4-fluoro-phenyl)-tropane) was examined in membrane homogenates prepared from fresh rat caudate-putamen. The number of rinses of the membranes following incubation with the ligand was varied. After one wash, only a single binding site was evident. With an increasing number of washes, however, two binding sites were observed. Additional rinses, up to a total of four, led to a decrease in the number of low affinity binding sites, with no change in the number of high affinity sites. These results suggest that the methodology used in these binding assays may be important for interpretation of the results. PMID- 8464333 TI - Ambient temperature effects on thermoregulation and endurance in anticholinesterase-treated rats. AB - In sedentary animals, physostigmine (PH) administration resulted in a decreased core temperature that is ambient temperature (Ta) dependent. PH administration in rats exercising on a treadmill (26 degrees C, 50% rh, 11m/min, 6 degrees incline) decremented endurance and increased rate of rise of core temperature (heating rate, HR). This study was undertaken to examine the effects of Ta on the endurance and thermoregulatory decrements of PH-treated running rats. Adult male rats (510-530g) were given either 0.2ml saline (C) or 100 ug/kg physostigmine salicylate in 0.2 ml saline via tail vein 15 min prior to the start of running to exhaustion at 10, 15, 26, or 30 degrees C. In both C- and PH-treated groups, endurance decreased and HR increased with increasing Ta from 15 to 30 degrees C. At 15 and 26 degrees C the C rats ran significantly (p < .05) longer and had significantly lower HR than the PH rats: C15 = 90 +/- 8 min, 0.022 +/- 0.006 degrees C/min; C26 = 67 +/- 6, 0.051 +/- 0.007; PH15 = 57 +/- 5, 0.052 +/- 0.008; and PH26 = 43 +/- 6, 0.092 +/- 0.007. At 10 and 30 degrees C there were no significant differences between C and PH-treated rats. A Ta of 30 degrees C was too high for effective cooling in either group, and at 10 degrees C both groups were able to dissipate heat despite the increased metabolic rate of the PH treated rats. The PH-treated rat model of cholinergic drug effect is useful at a Ta of 15 and 26 degrees C. PMID- 8464334 TI - Single injection of pentobarbital induces long-lasting effects on ANP synthesis and gene expression in the rat atria. AB - To define the long-term effects of pentobarbital sodium on the plasma and atrial atrial natriuretic peptide (ANP) system, experiments were performed in female Sprague-Dawley rats. The plasma levels of immunoreactive (ir) ANP showed chronic as well as acute response to pentobarbital sodium administration. A single dose (30 mg/kg, i.p.) of pentobarbital sodium resulted in a suppression in the plasma levels of irANP up to 1 week of administration. The suppressive effect on plasma irANP concentrations was dose-dependent. Right but not left atrial contents of irANP increased by an administration of pentobarbital sodium up to 4 weeks. ANP mRNA contents of the atrial exposed to pentobarbital sodium began to increase after 2 days, reached to the peak after 2 weeks, and began to return to control values after 6 weeks. Surgical stress accentuated these patterns of plasma and atrial ANP responses to pentobarbital sodium treatment. The present data, therefore, suggest that even a single anesthetic dose of pentobarbital could elicit long-lasting profound changes in ANP system, i.e., changes in gene expression, synthesis and the secretion of ANP. PMID- 8464335 TI - Receptors implicated in the actions of serotonin on chicken ileum longitudinal smooth muscle. AB - The presence of serotonin (5-HT) in the chicken gastrointestinal tract has been previously reported, but its motor effects have been poorly described. The aims of this work were: A) to define the effects of 5-HT on chicken longitudinal ileum; B) to explore the mechanisms by which such effects occur and C) to identify the subtype(s) of 5-HT-ergic receptors implicated. The motor responses to 5-HT were assayed in vitro using ileal strips taken from male White Leghorn chickens 7-9 week old. 5-HT elicited ileal contraction (EC50 9.6 x 10(-8) M), which was markedly decreased in the presence of tetrodotoxin (TTX). Repeated exposure of the tissue to supramaximal concentrations of 5-HT did not however lead to desensitization. Atropine (10(-6) M), ketanserin (10(-5) M), methysergide (10(-5) M) and methiothepine (10(-6) M) attenuated the response to 5-HT. Ketanserin was an effective inhibitor of the residual response to 5-HT obtained even in the presence of TTX. Several serotonergic agonists were assayed to further analyse the type of receptors involved in the response to 5-HT. 5 methoxytryptamine (5-MOT), a mixed 5-HT1, 5-HT2 and 5-HT4 agonist, reproduced all the effects of 5-HT. 8-OH-DPAT, a selective 5-HT1A agonist, trifluoromethylphenylpiperazine, a mixed 5-HT1B/C agonist, and m chlorophenylbiguanide, a 5-HT3 agonist, did not induce any consistent contractile effects. Sumatriptan, a 5-HT1D agonist, exerted a slight agonistic effect which was blocked by methiothepine and decreased by TTX but not by atropine. Cisapride, a 5-HT4 partial agonist in mammals, decreased the effects of both 5-HT and 5-MOT. These results indicate that chicken ileum contains 5-HT1 receptors similar to the 5-HT1D mammalian subtype but not the 5-HT1A, 5-HT1B, 5-HT1C or 5-HT3 subtypes. 5 HT2 receptors are also present and would appear to be located on smooth muscle. PMID- 8464336 TI - Lymphatic transport of eicosapentaenoic and docosahexaenoic acids as triglyceride, ethyl ester and free acid, and their effect on cholesterol transport in rats. AB - Lymphatic transport of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids given in the forms of triglyceride, ethyl ester of free acid and their effect on cholesterol transport was compared in lymph-cannulated rats. Lymphatic recovery of DHA and EPA given by stomach tube in the form of triglyceride in which they were mainly located at the 2-position was significantly higher than that of the ethyl ester or free acid during the first 6 hr after the administration and the tendency continued until 9 hr. In contrast, the 9 to 24 hr recovery of DHA and EPA in the forms of ethyl ester and free acid was considerably higher than that of triglyceride. Consequently, cumulative 24 hr recovery of EPA was comparable among the three forms. However, the 24 hr recovery of DHA was highest in free acid, lowest in ethyl ester and intermediate in triglyceride. Recovery of the free acid between 9 and 24 hr after administration was significantly higher than that given in the forms of triglyceride or ethyl ester. Cholesterol recovery in lymph of rats given with ethyl ester or free acid was lower than that given with triglyceride at an early stage after the administration in both EPA and DHA. Cumulative 24 hr recovery of cholesterol in rats given these fatty acids as ethyl ester was significantly lower than in those given as the other two forms. PMID- 8464337 TI - Transforming growth factor-alpha activity in effusions: comparison of radioimmunoassay and radioreceptorassay. AB - Transforming growth factor-alpha (TGF-alpha) in pleural and peritoneal effusions was assayed by homologous radioimmunoassay (RIA) and radioreceptor assay (RRA) using human placental membrane. Effusions were obtained from 24 patients with and 17 patients without cancer. Most of the effusions were found to contain TGF-alpha by RIA and RRA, but immunoreactive epidermal growth factor (EGF) was not detected. Effusions were chromatographed on Bio-Gel P-60 with several peaks of TGF-alpha activity by both RIA and RRA. A discrepancy in the chromatographic pattern of TGF-alpha between RIA and RRa suggested the existence of EGF-like substances capable of binding to EGF receptors which lack immunoreactivity for EGF or TGF-alpha. The TGF-alpha concentration of the acetic acid-extracted malignant effusions assayed by RRA significantly exceeded the value obtained from benign effusions (17.0 +/- 8.7 vs. 9.2 +/- 6.3 ng/ml; mean +/- SD: p < 0.02). However, the concentrations obtained by RIA did not differ. PMID- 8464338 TI - Central cocaine neurotoxicity at brainstem cardiorespiratory control sites. AB - Cocaine hydrochloride was applied topically to the ventrolateral medullary surface (VMS) where chemosensitive respiratory and vasomotor control sites are colocalized. Cats (n = 16) were anesthetized with urethane (2.0 g/kg, 80 percent of dose titrated over 60 min). The trachea of each animal was cannulated and the VMS was surgically exposed. Tidal volume (VT), frequency of breathing (f), systolic and diastolic blood pressure (SBP and DBP, respectively), and heart rate (HR) were measured. Cocaine (62.5 micrograms per site) administered at the VMS control sites decreased f, SBP, and DBP significantly (p < 0.05), without changing HR or VT values. This cocaine-induced hypoventilation was associated with brief intervals of inspiratory cramp (apneusis). Central cocaine neurotoxicity may result from interaction of cocaine with VMS sites, producing increased inspiratory drive and decreased vasomotor tone. PMID- 8464339 TI - Priming with murine recombinant interleukin-5 resulted in the augmentation of PAF induced airway hyperresponsiveness to histamine in guinea pigs. AB - The effects of pretreatment with murine recombinant interleukin 5 (mrIL-5) on platelet activating factor (PAF)-induced bronchoconstriction and airway hyperreactivity were investigated in guinea pigs. The intratracheal administration of mrIL-5 (2.5-10 micrograms) augmented platelet activating factor (PAF; 50 ng/kg)-induced bronchoconstriction in guinea pigs. When IL-5 (2.5 micrograms) was injected intratracheally, PAF (25 ng/kg)-induced bronchoconstriction was not affected, but PAF-induced airway hyperresponsiveness to histamine was exacerbated. Airway inflammation, in terms of increased capillary permeability and the accumulation of leukocytes in bronchoalveolar lavage fluid, was not produced by pretreatment with PAF (25 ng/kg), mrIL-5 (2.5 micrograms), or by a combination of these agents. This mrIL-5-induced augmentation of airway hyperreactivity by PAF was clearly inhibited by the phosphodiesterase-type III inhibitors, SDZ-MKS-492 and AH 21-132, but not by aminophylline. PMID- 8464340 TI - Lack of bupivacaine kinetic changes induced by flumazenil in mice. AB - This study was designed to document possible changes in bupivacaine kinetics in mice after a single 1 mg/kg injection of flumazenil. After a single 20 mg/kg i.p. dose of bupivacaine, C max, Vd, Cl and AUC were not significantly modified by flumazenil; even if T max was shown to be significantly shorter when flumazenil was associated, bupivacaine bioavailability did not seem to be modified and thus may not be involved in the explanation of previously reported increasing bupivacaine-induced mortality by flumazenil. PMID- 8464341 TI - Vascular smooth muscle and nitric oxide. AB - Experiments were performed to investigate the production of endothelium-derived relaxing factor (EDRF or nitric oxide; NO) by vascular smooth muscle cells. The lumen of bovine pulmonary arteries were filled with Krebs-Henseleit solution (incubates). Both endothelium-intact and endothelium-deprived vessels were used. Incubate solutions from the lumen of generator vessels contained a significant amount of nitric oxide (NO). Although the NO concentration was higher in incubates from endothelium-intact vessels, endothelium-deprived vessels also produced NO. The length of incubation did not influence the amount of nitric oxide released. Endothelium-deprived pulmonary arteries also generated NO as detected by chemiluminescence. The amount produced however was not sufficient to relax endothelium-deprived detector vessels in superfusion bioassay experiments. Samples from Krebs-Henseleit (K-H) solution surrounding the preparation (bathing solution) contained NO values which were also significantly higher than the control. Nitric oxide found in the bathing solution also appeared to originate from endothelium and vascular smooth muscle. Oxyhemoglobin attenuated NO signals. The results demonstrate that nitric oxide is released by vascular smooth muscle cells as well as by endothelium. However, the amount of NO released by muscle is insufficient to relax endothelium-deprived vascular preparations. PMID- 8464342 TI - Acute hyperinsulinemia increases neuropeptide Y concentrations in the hypothalamic arcuate nucleus of fasted rats. AB - Neuropeptide Y, a major hypothalamic peptide, stimulates feeding, insulin secretion and weight gain when injected intrahypothalamically. Hypothalamic NPY may be regulated by insulin availability at hypothalamic level, as its activity is apparently inhibited by intrahypothalamic insulin administration and is stimulated under insulin-deficient conditions. To determine the effects of acute physiological hyperinsulinemia, we measured regional hypothalamic NPY levels in rats during a hyperinsulinemic, euglycemic clamp. Seven male Wistar rats with implanted jugular cannulae, fasted for 24 h, were infused with insulin at 100 mU/h together with variable-rate glucose to maintain euglycemia (3.9 +/- 0.1 mmol/l), for 150 min. Controls were infused for the same period with polygeline vehicle alone (n = 8), and had blood glucose concentrations of 4.0 +/- 0.5 mmol/l. Insulin levels were 80.2 +/- 3.9 mU/l in insulin-infused rats and 15.2 +/ 1.4 mU/l in polygeline-treated controls (p < 0.001). NPY levels, measured by radioimmunoassay, were significantly higher in the arcuate nucleus/median eminence (ARC/ME) of hyperinsulinemic rats than in controls (4.8 +/- 1.2 vs 2.5 +/- 0.6 fmol/micrograms protein; p < 0.001), but were comparable with controls in 7 other hypothalamic regions. Acute physiological hyperinsulinemia therefore increases NPY levels selectively in the ARC/ME. Insulin could cause NPY accumulation in the ARC by blocking its transport to NPY-sensitive areas. This would be consistent with the suggestions that insulin inhibits hypothalamic NPY activity and also acts as a central satiety factor. PMID- 8464343 TI - Direct vasopressor effects of erythropoietin in genetically hypertensive rats. AB - The purpose of this study is to compare the direct vasopressor effects of erythropoietin between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The aortic rings from SHR or WKY were suspended in tissue baths coupled with tension-recording devices. High concentrations of recombinant human erythropoietin (more than 20 U/ml) induced vasoconstriction in the aortic ring of genetically hypertensive SHR. Furthermore, only in SHR, 10 U/ml erythropoietin enhanced contraction induced by 10(-7) M norepinephrine (+145% vs +121%, p < 0.04) and reduced relaxation by 10(-7) M acetylcholine (-69% vs -96%, p < 0.05). On the other hand, erythropoietin did not influence the contractility of aortic ring in normotensive WKY. These results suggest that erythropoietin exhibits its direct vasopressor effect preferentially in the blood vessels of genetically hypertensive animals. PMID- 8464344 TI - Anticonvulsant effects of intracerebroventricularly administered norepinephrine are potentiated in the presence of monoamine oxidase inhibition in severe seizure genetically epilepsy-prone rats (GEPR-9s). AB - Pharmacological and neurochemical evidence indicates that brain noradrenergic systems play an important role in the determination of audiogenic seizure severity in genetically epilepsy-prone rats (GEPRs). In earlier studies, intracerebroventricular (ICV) injections of norepinephrine suppressed convulsions in a now extinct moderate seizure GEPR colony. Also, ICV noradrenergic agonists are known to produce dose-related anticonvulsant effects in the extant moderate seizure GEPRs (GEPR-3s). The present experiments were undertaken to determine whether ICV norepinephrine also suppresses audiogenic seizures in the extant GEPR 3s and in the severe seizure genetically epilepsy-prone rats (GEPR-9s). Injections of norepinephrine or vehicle were made into the lateral ventricle through implanted guides. GEPR-9s were pretreated systemically either with the monoamine oxidase inhibitor pargyline or with saline. GEPR-3s received no pretreatment. In pargyline pretreated GEPR-9s, seizure severity fell and the fraction of animals exhibiting an anticonvulsant response increased progressively as the dose of norepinephrine was increased. In saline pretreated GEPR-9s, the anticonvulsant dose response curve for norepinephrine was shifted to a higher dose range. Accordingly, the anticonvulsant dose50 for norepinephrine was significantly greater in saline pretreated GEPR-9s than in pargyline pretreated animals. Moreover, the dose required to produce the anticonvulsant effect in GEPR 9s was approximately 10 fold greater than in the earlier studies in the extinct moderate seizure GEPRs. Also, the current experiment with extent GEPR-3s, showed that ICV norepinephrine was anticonvulsant in the same dose that was effective in the extinct colony of moderate seizure GEPRs. In general terms, these observations provide additional evidence that noradrenergic influences are anticonvulsant in the GEPR. The neurobiological factors responsible for reduced responsiveness of the GEPR-9 are presently unknown. PMID- 8464347 TI - Turnover of cholesterol and dipalmitoyl phosphatidylcholine in surfactant of adult rat lung. AB - In order to compare the turnover of two major surfactant components, [1 alpha,2 alpha (n)-3H]cholesterol and [methyl14C choline] dipalmitoyl phosphatidylcholine (DPPC) were introduced as lamellar bodies via the trachea into lightly anesthetized rats which were then allowed to recover. The radiotracers were assumed to have entered the alveolar surfactant pool and to have subsequently recycled in part into the lamellar bodies of alveolar type II cells. For DPPC, the specific activity vs. time curves of tubular myelin rich (alv-1) and tubular myelin poor (alv-2) alveolar lavage fractions were similar, and there was a plausible precursor-product relationship between lamellar bodies and either (or both) of these compartments. In contrast, however, the specific activities of alv 1 and alv-2 for cholesterol were quite different, allowing us to reject the hypothesis of a precursor-product relationship between classical lamellar bodies and alv-2. The estimated turnover time for DPPC in alv-1 was 240 or 206 min, depending on which subfraction of lamellar bodies one takes to be the precursor. For cholesterol it was 583 or 624 min. These longer turnover times for cholesterol should lead to a greater than twofold increase in the relative concentration of cholesterol in the putative product compartment. Such an increase was not found. We interpret this as reflecting either noncompartmental behavior of the alveolar surfactant pool, or multiple pools of lamellar bodies with different turnover times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464345 TI - Plasma-kallikrein clearance by the liver of acetaminophen-intoxicated rats. AB - The liver synthesizes prokallikrein and is the main organ to clear the active enzyme (plasma-kallikrein) from circulation. This clearance, a receptor-mediated endocytosis, is calcium-independent and not affected by the blockade of Kupffer cells. The effects of endothelial cells blockade and of acetaminophen intoxication on the clearance of 10 nM rat plasma-kallikrein (RPK) by the isolated, exsanguinated and perfused rat liver are now reported. Endothelial cells blockade obtained by the addition of large excess (30 uM) of formaldehyde treated serum albumin to the perfusion fluid does not affect the hepatic clearance of RPK (the half-lives of hepatic uptake were 15.5 +/- 1.0 min in the absence versus 16.5 +/- 1.4 min in the presence of the treated protein, p > 0.05). Some livers were perfused 24 hours after acetaminophen intoxication: 6.6 mmol/kg given i.p. after a 42-hour period of fast. Hepatocyte injury suggested by elevated aminotransferase activity (ALT 10 times control value, AST 30 times control value), acute phase inflammatory response (serum alpha 2-macroglobulin increase) and reduced synthetic function (serum albumin decrease), was confirmed histologically and only zone 3 hepatocytes were necrotic. A 66-hour period of fast does not affect by itself the hepatic clearance of RPK (16.9 +/- 1.3 min of half-life of hepatic uptake) when compared with the control group (15.5 +/- 1.0 min, p > 0.05). On the other hand the RPK clearance by the livers of rats previously intoxicated with acetaminophen was markedly deficient (the half-life of hepatic uptake was 39.2 +/- 3.2 min). These findings suggest that RPK is internalized by hepatocytes, preferentially by those of the perivenular zone of the hepatic acinus. PMID- 8464346 TI - The effects of dietary fish oil on alveolar type II cell fatty acids and lung surfactant phospholipids. AB - The purpose of this study was to determine the responsiveness of alveolar type II cells to dietary fish oil and the consequent effects on alveolar and lung surfactant. Rats were fed a corn oil or a fish oil diet for four weeks. Dietary n 3 fatty acids were readily incorporated into the type II cell phospholipids as indicated by higher levels of eicosapentaenoic acid (2.77 +/- 0.10%) and docosahexaenoic acid (1.63 +/- 0.10%) in the group receiving the fish oil diet. The elevated levels of n-3 fatty acids were accompanied by concomitant reduction in arachidonic acid and linoleic acid. Neither eicosapentaenoic acid nor docosahexaenoic acid was incorporated into type II cell triacylglycerols. Feeding a fish oil containing diet increased surfactant phospholipids, particularly 1,2 disaturated acyl phosphatidylcholines in whole lung compared to a corn oil diet. However, the amount of surfactant found in the alveolus was not different between the two diet treatment groups. The results suggest that dietary n-3 fatty acids stimulate synthesis and/or inhibit degradation of lung surfactant without altering surfactant secretion in alveoli. PMID- 8464348 TI - Hypolipidemic effects of beta-cyclodextrin in the hamster and in the genetically hypercholesterolemic Rico rat. AB - The effect of increasing amounts of a cyclic oligosaccharide, beta-cyclodextrin (BCD), included in the diet on plasma cholesterol and triglycerides, was investigated in two animal models, namely in male genetically hypercholesterolemic Rico rats and in male Syrian hamsters. The distribution of bile acids in the gastrointestinal tract and in the feces of hamsters was also determined. In the Rico rats and hamsters, plasma cholesterol and triglycerides decreased linearly with increasing doses of BCD. In these two species, 20% BCD as compared to control diet lowered cholesterolemia (-35%) and triglyceridemia ( 70%). In the hamster, the BCD diet caused a marked decrease in cholesterol and triglycerides in chylomicrons and very low density lipoprotein, and in high density lipoproteins cholesterol. Composition and amounts of bile acids were modified in the gastrointestinal tract of hamsters receiving 10% BCD as compared to the control group. The total bile acid content of the gallbladder of treated hamsters was fourfold higher than in the control group, and the bile contained a large amount of hydrophilic bile acids. This trend was also observed in the small intestine, in which percentages and total quantities of cholic plus deoxycholic acids (cholic pathway) were higher than those of chenodeoxycholic plus ursodeoxycholic plus lithocholic acids (chenodeoxycholic pathway). The bile acid contents of the cecum and colon of treated hamsters were 2.7-fold higher than those of control animals, but the bile acid composition was similar in the two groups of hamsters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464350 TI - Human platelets release a paf-acether: acetylhydrolase similar to that in plasma. AB - Intact washed human platelets aggregated in response to paf-acether (paf) and did not metabolize [3H]paf at concentrations up to 10 nM. However, when platelets were lysed by exposure to pH 9.5, resulting in 37.5 +/- 2.5% (mean +/- SD, n = 3) lactic dehydrogenase (LDH) release, 20.5 +/- 5.7% of the radioactivity was detected as labeled lyso paf and 5.7 +/- 3.1% as labeled alkylacylglycerophosphocholine. When platelets were aggregated with 0.5 IU/mL thrombin or high concentrations of paf (100 nM), they released a part of their acetylhydrolase without releasing LDH. In supernatants obtained from aggregated platelets, 21 +/- 2% or 10 +/- 2% (n = 3), respectively, of the total platelet acetylhydrolase activity was detected vs. none in supernatants of resting cells. The release of acetylhydrolase was concentration- and time-dependent and paralleled the release of PF 4, a marker for alpha-granules. The acetylhydrolase affinity for paf (Km) measured in sonicates of resting and thrombin-activated platelets was 8.3 +/- 1.5 microM vs. 10.6 +/- 1.5 microM, n = 5, n.s. in a "Mann Whitney" test. The latter Km was slightly but significantly different (P < 0.05, n = 5) from that of the thrombin-released acetylhydrolase (7.9 +/- 1.5 microM) and that of the latter was itself different from plasma acetylhydrolase (5.3 +/- 0.5, P < 0.05, n = 5). Addition of plasma (acid-treated to inactivate acetylhydrolase) decreased the Km value of supernatant acetylhydrolase to 6.1 +/- 1.4 microM. All preparations of acetylhydrolase exhibited similar pH requirements and sensitivity to various inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464351 TI - Reaction of alpha-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate. AB - alpha-Tocopherol was reacted with alkyl and alkylperoxyl radicals at 37 degrees C in bulk phase. The lipid-free radicals were generated by the reaction of methyl linoleate with the free radical initiator, 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) under air-insufficient conditions. The products were isolated by high performance liquid chromatography. Their structures were identified as 2-(alpha tocopheroxy)-2,4- dimethylvaleronitrile (1), a mixture of methyl 9-(8a-peroxy alpha-tocppherone)-10(E),12(Z)-octadecadienoate and methyl 13-(8a-peroxy-alpha tocopherone)-9(Z),11(E)-octadecadienoate (2), methyl 9-(alpha-tocopheroxy) 10(E),12(Z)-octadecadienoate (3a), methyl 13-(alpha-tocopheroxy)-9(Z),12(E) octadecadienoate (3b), alpha-tocopherol spirodiene dimer (4) and alpha-tocopherol trimer (5). When methyl linoleate containing alpha-tocopherol was oxidized with AMVN under air-sufficient conditions, the main products were 8a-alkylperoxy-alpha tocopherones (2). In addition to these compounds, 6-O-alkyl-alpha-tocopherols (1, 3a and 3b) were formed when the reaction was carried out under air-insufficient conditions. The results indicate that alpha-tocopherol can react with both alkyl and alkylperoxyl radicals during the autoxidation of polyunsaturated lipids. PMID- 8464349 TI - The effect of culture medium composition on ether lipid cytotoxic activity. AB - The effect of a serum-free medium (TNB-100), compared to RPMI 1640 containing 10% fetal bovine serum (FBS), on the lipid composition of HL60 and K562 leukemic cells was investigated. The 10% FBS RPMI medium contained approximately three times more phospholipids (PL), about three times more protein and eight times more cholesterol (CHOL) than did the TNB-100 medium. Cells cultured in TNB-100 medium, referred to as HL60-TNB and K562-TNB cells, were significantly lower in PL and CHOL than 10% FBS RPMI cells, with about a threefold higher PL-to-CHOL ratio; however, these cells were significantly higher in protein content. Cells grown in TNB-100 were also significantly more fluid than 10% FBS RPMI cells and were more sensitive to the fluidizing action of the ether lipid 1-O-octadecyl-2-O methyl-rac-glycero-3-phosphocholine. The 50% inhibitory dose of the drug was about 50% lower in TNB-grown cells than in 10% FBS RPMI cells. PMID- 8464352 TI - Triacylglycerols of human milk: rapid analysis by ammonia negative ion tandem mass spectrometry. AB - Human milk triacylglycerols (TAG) were analyzed by ammonia negative ion chemical ionization tandem mass spectrometry. The deprotonated molecular ions of triacylglycerols were fractionated at the first mass spectrometry (MS) stage. Twenty-nine of the deprotonated TAG ions were further analyzed based on their collisionally activated (CA) spectra. The tandem MS analysis covered eleven major acyl carbon number fractions, two of which contained odd carbon number fatty acids. Fatty acids of 28 different molecular weights were recorded from the daughter spectra. Hexadecanoic acid was present in all CA spectra, octadecenoic acid in the CA spectra of all mono- and higher unsaturated TAG, and octadecadienoic acid in the CA spectra of all di- and higher unsaturated TAG. The major fatty acid combinations in triacylglycerols were: with 0 double bonds (DB), 12:0/12:0/16:0; with 1 DB, 12:0/16:0/18:1; with 2 DB, 16:0/18:1/18:1; with 3 DB, 16:0/18:2/18:1; with 4 DB, 18:2/18:1/18:1; and with 5 DB, 18:2/18:2/18:1; hexadecanoic acid typically occupied the sn-2 position. The most abundant TAG was shown to be sn-18:1-16:0-18:1, comprising about 10% of all triacylglycerols. PMID- 8464353 TI - Hypolipidemic activity of 6-alkoxycarbonyl-3-aryl-1,3,5- triazabicyclo[3.1.0]hexane-2,4-diones and 2-alkoxycarbonyl-5-aryl-1,3,5-triazine 4,6(1H,5H)-diones in rodents. AB - Significant hypolipidemic activity was demonstrated by 6-ethoxycarbonyl-1-3 phenyl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-dione, 2-ethoxycarbonyl-5-phenyl 1,3,5-triazine-4,6(1H,5H)-dione and 2-ethoxycarbonyl-5-(4-chlorophenyl)-1,3,5 triazine-4,6(1H,5H)-dione in rodents at 20 mg/kg/day. These agents lowered serum cholesterol and triglyceride levels by approximately 40% in mice after 16 d. Tissue lipids in rat liver, small intestinal mucosa, aortic wall and feces were reduced by treatment with the agents. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol levels were reduced in the rat; high density lipoprotein (HDL) cholesterol levels were elevated after 14 d of treatment. The activities of regulatory enzymes, e.g., acetyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, cholesterol 7 alpha-hydroxylase, sn glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase, involved in de novo synthesis of hepatic lipids were affected by the agents. The new compounds may represent another class of potentially useful hypolipidemic agents for the treatment of atherosclerosis since HDL cholesterol levels were increased and VLDL and LDL cholesterol levels were lowered by some of the agents. PMID- 8464355 TI - Simultaneous determination of the main molecular species of soybean phosphatidylcholine or phosphatidylethanolamine and their corresponding hydroperoxides obtained by lipoxygenase treatment. AB - A method for the simultaneous determination of the main molecular species of soybean phosphatidylcholine or phosphatidylethanolamine and their corresponding hydroperoxides is described. Hydroperoxides were formed by incubation of phospholipids with lipoxygenase at pH 9.2. Silicic acid column chromatography (silica Sep-Pak column) was used to separate the phospholipids into phosphatidylcholine and phosphatidylethanolamine. A single C-18 reverse-phase column was employed to separate the main molecular species of soybean phosphatidylcholine or phosphatidylethanolamine and their hydroperoxides by high performance liquid chromatography. The mobile phase consisted of 5% 10 mM ammonium acetate at pH 5 and 95% methanol. The molecular species of phosphatidylcholine and phosphatidylethanolamine were detected at 205 nm; the eluate was mixed with a chemiluminescence reagent (isoluminol and microperoxidase) and monitored by fluorometry. Under the experimental conditions used, three individual molecular species of both soybean phosphatidylethanolamine and phosphatidylcholine (18:3/18:2, 18:2/18:2 and 16:0/18:2), together with their corresponding hydroperoxides, were identified and quantitated. PMID- 8464354 TI - Antagonism of [3H]fatty acid incorporation into vimentin by sodium pyruvate: pitfalls of protein acylation. AB - In the course of studying possible fatty acid acylation of vimentin by cultured bovine lens epithelial cells, several potential pitfalls of protein-fatty acid acylation were recognized. Even exhaustive delipidation of vimentin with organic solvents failed to remove all noncovalently associated [3H]palmitate and [3H]myristate. Hydroxylamine treatment of vimentin, separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), failed to remove either palmitate or myristate derived radiolabel. Hydroxylamine treatment did remove palmitate label from a group of lower molecular weight proteins. The myristate radiolabel associated with vimentin recovered after SDS-PAGE and subjected to acid hydrolysis was shown due to incorporated [3H]amino acids, mainly glutamic acid, generated from the fatty acid. Adding excess sodium pyruvate to labeling media has been used by others to reduce the metabolic conversion of fatty acids to amino acids; however, no direct evidence in support of this antagonism was presented. We observed that inclusion of sodium pyruvate at between 5 and 20 mM in the labeling medium produced a dramatic decrease in incorporation of myristic acid radiolabel into vimentin. However, inclusion of even 20 mM pyruvate did not completely antagonize the metabolic conversion of fatty acid label to amino acids. Furthermore, the sodium pyruvate antagonism could be totally obscured if the exposure of X-ray film by fluorography was even slightly prolonged. The results illustrate the danger in assuming that solvent extraction totally delipidates proteins and that adding sodium pyruvate to labeling media prevents the transfer of fatty acid label to amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464357 TI - Zinc and red cell fatty acid composition. PMID- 8464356 TI - A thermospray mass spectrometric assay for Fe-induced 4-hydroxynonenal in tissues. AB - A method is presented for the determination of 4-hydroxynonenal (HNE) in tissue homogenates following in vitro lipid peroxidation induced by iron (Fe++). HNE is measured as the pentafluorobenzyl oxime derivative using liquid chromatography thermospray mass spectrometry. In vitro metabolism of HNE via the glutathione/glutathione-S-transferase pathway was inhibited using iodoacetic and iodobenzoic acids. The assay has been used as an indicator of the peroxidizability of tissue samples from animals both adequate in and depleted of alpha-tocopherol. The concentrations of HNE produced in tissues taken from animals depleted of alpha-tocopherol were found to be up to 8 times higher than those taken from animals supplemented with alpha-tocopherol. PMID- 8464358 TI - Phased spectroscopic images: application to the characterization of the 1H 1.3 ppm resonance in intracerebral tumors in the rat. AB - Spectra obtained with phase-encoding techniques show phase-shifts varying from voxel to voxel. The procedure allowing voxel-dependent phase-shifts to be compensated is presented. The method has been applied to the characterization of the 1.3-ppm resonance observed in intracerebral tumors in the rat. PMID- 8464359 TI - Nuclear magnetic resonance Hahn spin-echo decay (T2) in live rats with endotoxin lung injury. AB - To determine the possibility of using nuclear magnetic resonance imaging to study experimentally induced lung injury, we measured in the lungs of spontaneously breathing living rats the time course of both the Hahn spin-echo decay (T2) and the proton density after endotoxin injury. In order to minimize artifacts arising from motions of the nearby chest wall and heart, we used a motion-insensitive technique (the interleaved line scan). A typical Hahn T2 measurement was obtained over a region of interest from a series of images each with a different echo time, which ranged from 16 to 110 ms. Lung water content was determined by integrating the proton density over the region of interest. The Hahn T2 and proton density were measured before and at 1, 3, 6, and 9 h after intravenous injection of endotoxin. The effects of the treatment administered before and after endotoxin injection were also evaluated. Endotoxin treatment caused lengthening of both fast (T2f) and slow (T2s) Hahn T2 components but had no significant effect on the proton density, consistent with the notion that endotoxin causes lung injury without significant lung water accumulation in rats. However, the methylprednisolone treatment prevented the lengthening of T2s but did not seem to have a significant effect on T2f. Our results suggest that NMR imaging can be used to detect and monitor experimental lung injury in intact living animals, even in the absence of variations of lung water content. PMID- 8464360 TI - Imaging oxygen tension in liver and spleen by 19F NMR. AB - 19F NMR imaging of the perfluorocarbon emulsion Fluosol has been used to study regional variations in oxygen tension in rat liver and spleen. We have used the linear dependence of spin lattice relaxation rate (1/T1) on the partial oxygen pressure (pO2) of Fluosol to determine the oxygen tension in the reticuloendothelial system (RES) of the liver and spleen of male Sprague-Dawley rats which have received serial infusions of Fluosol. Oxygen tension maps have been computed from 19F NMR images using a calibration obtained for Fluosol in vitro at 37.5 degrees C. The spatial resolution of the pO2 maps computed using this technique is 1.2 x 1.2 mm in 3-mm thick slices. Calculations from in vivo pO2 maps indicate an average change in the median pO2 of the RES from 118 to 80 mmHg for (n = 7) rats breathing 95% O2 and 5% CO2 (carbogen) and air, respectively. PMID- 8464361 TI - Field dependent transverse relaxation rate increase may be a specific measure of tissue iron stores. AB - The degree to which MRI magnet field strength affects measured transverse relaxation rates (R2) defines a measure termed the field dependent R2 increase (FDRI). We report here the results of in vivo and in vitro experiments that were conducted to evaluate whether FDRI is a potentially useful measure of tissue iron stores. T2 relaxation times were obtained using two clinical MRI instruments operating at 0.5 and 1.5 Tesla, and relaxation rates (R2) were calculated as the reciprocal of T2. The in vivo experiment measured R2 in human brain frontal white matter, caudate nucleus, putamen, and globus pallidus. The FDRI was very highly correlated with published brain iron levels for the four regions examined. The in vitro experiment measured R2 in agarose gel-based phantoms containing physiologic forms and amounts proteins involved in iron storage and transport (ferritin, apoferritin, transferrin, and apotransferrin). Significant field dependence was observed only for the ferritin phantoms. The differences in the R2 values obtained at the two field strengths were striking, and were proportional to the ferritin levels of the phantoms. These studies suggest that FDRI may be a specific measure of tissue ferritin. The quantitative significance of the results to imaging and possible applications to the clinical investigation of pathologic states are discussed. PMID- 8464362 TI - A technique for assessment of bone marrow composition using magnetic resonance phase interference at low field. AB - In disorders which involve the bone marrow, the fat/water ratio of the marrow is often an indicator of the progress of disease. A noninvasive method of monitoring this ratio in bone marrow could be clinically useful. We have investigated a method of bone marrow assessment, using magnetic resonance imaging at low field (0.064 Tesla). The method has been tested using calibrated phantoms; we also present results from normal human subjects. PMID- 8464363 TI - RF pulse design using the inverse scattering transform. AB - The inverse scattering transform (IST) is a mathematical transformation that can be used to derive RF pulses from functions called continuous spectra describing the final state of the spin system. This paper reviews three seemingly unrelated numerical algorithms that have appeared in the literature, and shows that they are all derivable from the IST. When the continuous spectra are rational, the finite rank kernel method is used to convert the IST to a matrix equation that is easily solved. Another algorithm, equivalent to the so-called "layer stripping" algorithm used in seismology, is derived by assuming that the spectra are Fourier series. Finally, the Shinnar-Le Roux (SLR) algorithm is derived by assuming that the spectra are ratios of Fourier series. With proper interconversion between the rational, series, and ratio of series forms of the continuous spectra, these algorithms generate RF pulses with identical or nearly identical shapes and performance properties, and can be regarded as equivalent. PMID- 8464364 TI - Diffusion imaging of experimental allergic encephalomyelitis. AB - Diffusion-weighted magnetic resonance imaging (MRI) was compared with T2-weighted MRI in longitudinal studies of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, in five monkeys (Macaca fascicularis). In a region of the brain that had highly directional myelinated fibers (internal capsule) sequential changes were identified on diffusion-weighted images on and before the day these changes were detected on conventional T2-weighted images. Changes were also identified on diffusion-weighted images in brain areas that did not develop T2-weighted abnormalities. This result suggests that diffusion weighted image intensities are sensitive to pathologic conditions of the brain that can not be seen on T2-weighted images. PMID- 8464365 TI - Contrast-enhanced first pass myocardial perfusion imaging: correlation between myocardial blood flow in dogs at rest and during hyperemia. AB - The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI. PMID- 8464366 TI - MRI gradient waveform design by numerical optimization. AB - This manuscript describes a method of gradient waveform design by nonlinear constrained optimization. Methods of formulation and solution of the waveform optimization problem are briefly described for minimization of root mean squared current and minimization of waveform moments. Waveforms generated using these objectives are presented and compared with those obtained with other objectives. The method uses waveforms which are defined as a set of discrete amplitudes in order to remove artificial constraints on waveform shape imposed by "multilobe" designs. These point-to-point amplitudes are the parameters determined in the optimization procedure which includes knowledge of the specific imaging conditions and the specific gradient hardware system. Some beneficial results of this design approach are: a) physically realizable waveforms which optimally achieve specific imaging and motion artifact reduction goals, b) waveforms which are guaranteed to be optimal with respect to one of several possible objective, c) less reliance on the experience of the designer, and d) a potential reduction in waveform design time. PMID- 8464367 TI - Phosphonate-modified Gd-DTPA complexes. III: The detection of myocardial infarction by MRI. AB - The potential of a phosphonate-modified-Gd-DTPA for MR image enhancement of myocardial infarction has been demonstrated in imaging experiments on rats. The agent, 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified-Gd-DTPA (Gd-DTPA-HPDP) accumulates in two models of myocardial infarction, (i.e., drug-induced diffusely infarcted whole hearts and in focal acute myocardial infarction from a left coronary artery ligation). The time course of the accumulation of the agent in the focal model of infarction and subsequent washout has also been followed in vitro. Results of this kinetics demonstrate that the agent first perfuses all normal fluid spaces and then slowly diffuses into the occluded zone where it is retained for a prolonged period, in sufficient quantities to be useful as an MRI contrast agent. Wash-out of the agent from normal myocardium is fast and complete with MR signal returning to background in minutes. The specificity of Gd-DTPA HPDP for soft-tissue calcification and its retention within the infarcts permitted imaging at 1 to 2 h postinjection, (after unbound material has cleared the normal tissues). Infarcted tissue appeared as regions of increased signal intensity in T1-weighted images (> 200% enhancement), and correlated with histopathology. Unmodified Gd-DTPA was not retained under identical conditions. Gd-DTPA-HPDP permits a more accurate infarct delineation than is possible with the unmodified agent. PMID- 8464368 TI - A weighted least-squares method for nuclear magnetic resonance velocity imaging. AB - The phase method for velocity measurements in NMR imaging with more than two velocity encoding steps is discussed. The weighted least-squares method takes into account the variation in the accuracy of phase calculations at a voxel with the size of the velocity encoding gradients. We choose the weights so that the method is equivalent to the method of maximum-likelihood for high signal-to-noise ratios. We propose a method of implementation to minimize the problem of phase wrapping. We also discuss the number of velocity encoding steps, the choice of step size, and signal averaging, to improve the reproducibility of velocity measurements. Standard deviation images for the velocity have been calculated and used to reduce velocity noise by thresholding the velocity image. PMID- 8464369 TI - High-resolution variable flip angle 3D MR imaging of trabecular microstructure in vivo. AB - Two conceptually related variable-flip-angle 3D spin-echo pulse sequences were designed for imaging at voxel sizes of 2-5 x 10(-3) mm3 corresponding to pixel areas of less than 100 x 100 microns2 and section thicknesses on the order of 300 400 microns on a conventional 1.5 T MR imaging system equipped with 1 G/cm imaging field gradients, providing 12 sections in 10 min imaging time. The pulse sequences make use of the concept of restoring longitudinal magnetization inverted by the 180 degrees phase reversal pulse and are derivatives of pulse sequences previously dubbed "FATE" and "RASEE." It is shown that even in the small-voxel regime (< 10(-2) mm3 voxel size) and at echo times on the order of 10 ms, gradient echo images are sensitive to intrinsic fields causing artifactual boundary effects, including signal loss from intravoxel phase scrambling and spatial mismapping. At this resolution the variable flip-angle spin-echo pulse sequences are demonstrated to be better suited for imaging magnetically heterogeneous systems such as trabecular bone microstructure in vivo. These pulse sequences are found to be substantially less sensitive to distortions from magnetic dipole fields occurring at the boundaries of two phases of different magnetic permeability. PMID- 8464370 TI - Noninvasive analysis of aldose reductase activities in rat testis: 3-FDG NMR spectroscopy and imaging. AB - Noninvasive investigation of aldose reductase activities in rat testis was performed using 3-fluoro-3-deoxy-D-glucose (3-FDG) and nuclear magnetic resonance (NMR) spectroscopy/imaging. Quantitative determination of testis aldose reductase activities, expressed as the sorbitol index, showed a value similar to that of brain. Sorbitol imaging demonstrated aldose reductase activities in testis to be confined primarily to the central region of this organ. The 3-FDG 19F NMR method appears to have clinical potential in the evaluation of testicular function, especially that of spermatogenesis, noninvasively. PMID- 8464371 TI - The appearance of neutral lipid signals in the 1H NMR spectra of a myeloma cell line correlates with the induced formation of cytoplasmic lipid droplets. AB - The appearance of high resolution neutral lipid signals in the 1H NMR spectra of myeloma cells grown in the presence of oleate was shown to correlate with the appearance of cytoplasmic lipid droplets observable by electron microscopy. The spin-spin relaxation times of these lipid signals were similar to those measured previously for lipid resonances in other cell types. These data suggest that cytoplasmic lipid droplets could make a significant contribution to the neutral lipid signals observed in the 1H NMR spectra of some cells. PMID- 8464372 TI - Some contrast agents in oil well logging and in medical MRI. AB - Magnetite particles and paramagnetic ion chelates are used as contrast agents in both nuclear magnetism logging of oil wells and in medical MRI. An analytic expression for reduction of T2 for free precession signal decay (or gradient echoes) by magnetite particles does not depend on diffusion and agrees with published Monte Carlo computations. PMID- 8464373 TI - Pitfalls in MR measurement of tissue blood flow with intravascular tracers: which mean transit time? AB - Measuring tissue blood flow with NMR imaging of intravascular tracers is more difficult than measurements of tissue blood volume. One major obstacle to the application of the Central Volume Principle is the direct measurement of the mean transit time. In this note, we demonstrate that mean transit time (MTT), which relates tissue blood volume to blood flow via the Central Volume Principle, is not the first moment of the concentration-time curve for MR or CT imaging of purely intravascular tracers. However, while first moment methods cannot be used by themselves to determine absolute flow, we show that transit curves may provide a useful relative measure of flow, for example, by considering ratios of the first moments. PMID- 8464374 TI - Oxygen measurement inside an NMR magnet with a catheter electrode. AB - In this study we show the possibility of continuous oxygen tension measurement inside an NMR magnet without disturbance of simultaneous NMR data acquisition. Our modified Clark-type oxygen electrode has a fast response (2 s) and can be inserted deep into small bore NMR systems thanks to its small diameter (2 mm). PMID- 8464375 TI - A perifusion loop-gap resonator NMR probe for aerobic cell suspensions. AB - NMR studies of aerobic cell metabolism require that spectral data of high sensitivity and resolution be acquired from samples maintained under suitable conditions. The loop-gap resonator 31P NMR probe described here was designed for investigations of highly aerobic-dependent renal proximal tubules in an environment similar to those of conventional incubation flasks. The inherently higher sensitivity of the loop-gap resonator design and associated circuitry made it possible to obtain adequate spectra in short periods of time with small amounts of sample. Cellular physiological properties of perifused aerobic renal proximal tubule cell suspensions in the loop-gap resonator probe were found to be similar to equivalent tissue samples incubated in conventional flasks. Furthermore, the loop-gap perifusion probe was found to provide useful 31P NMR spectra of the kidney tubule system after acquisition times as short as 3 min. PMID- 8464376 TI - A wireless axial pair resonator. AB - A wireless axial pair resonator consists of two coils coupling inductively with a body coil, which is used as a signal transmitter and receiver. Computer simulations gave signal enhancements of 1.41 and 1.47 for the resonators of 15- and 20-cm diameter, whereas those of phantom studies gave 1.37 and 1.49. PMID- 8464377 TI - Diffusion in red blood cell suspensions: separation of the intracellular and extracellular NMR sodium signal. AB - It is shown that the signal of intracellular and extracellular sodium of red blood cells can be separated by a difference in diffusion. Comparison with proton diffusion experiments conducted in parallel showed that this difference was caused by restriction to the cell volume. The measured proton and sodium root mean square displacements agreed well with the cell dimensions. However, this experiment is limited to use in vitro by the required gradient strength. PMID- 8464378 TI - Development and characterization of an ergometer to study the bioenergetics of the human quadriceps muscle by 31P NMR spectroscopy inside a standard MR scanner. AB - A description is given of an ergometer made of nonmagnetic materials which fits into a standard whole body MR magnet. T2-weighted images show that exercise is highly specific for quadriceps muscles. The ergometer permits the noninvasive study of T2-related changes in the proton images of the leg as well as changes occurring in muscle bioenergetics during exercise and recovery. PMID- 8464379 TI - Metaphase chromosome and nucleoid differences between CHO-K1 and its radiosensitive derivative xrs-5. AB - The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive mutant isolated from CHO-K1 cells. The radiation sensitivity is associated with a defect in DNA double-strand break rejoining. Chromatin structure also appears altered in xrs-5 cells compared with the parental CHO-K1 cells. Metaphase chromosomes from xrs-5 are more condensed in appearance than CHO-K1 chromosomes. The overcondensed look is not the result of colcemid sensitivity. Electron microscopy studies suggest that xrs-5 metaphase chromosomes have larger loops of chromatin extending out from the chromosome core. There are also differences between CHO-K1 and xrs-5 cells in the size and fluorescence pattern of ethidium bromide-stained nucleoid preparations. These results suggest that there is a fundamental difference between CHO-K1 and xrs-5 in either the organization of the supercoiled loops of DNA attached to the nuclear matrix or in the nature of the proteins that attach the DNA to the matrix. These alterations in chromosome structure may underlie, in part, the radiation sensitivity of xrs-5 cells. PMID- 8464380 TI - Standardization of the 32P-postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts. AB - A modified method for the 32P-postlabeling assay that permits standardized quantitation for specific polycyclic aromatic hydrocarbon (PAH)-DNA adducts is described. This method has been designed to test the components of the 32P postlabeling assay for use in the chemically specific detection of individual adducts with the ultimate goal of testing the biological significance of PAH-DNA adducts in humans. The approach relies upon high performance liquid chromatography (HPLC), concomitant labeling of 2'-deoxyguanosine (dGp) as an internal standard and thin layer chromatography (TLC), which identifies unmodified nucleotides along with PAH-DNA adducts on the same TLC plate. This method assesses labeling efficiency, detects the presence of unknown inhibitors, assesses the adequacy of digestion (when combined with HPLC) and allows for the development of calibration curves for directly determined molar ratios (adduct:internal standard). Chemically synthesized adduct standards and quantitative 32P-postlabeling data have been corroborated by UV spectroscopy, fluorescence spectroscopy and liquid scintillation counting where radiolabeled materials were available. Labeling efficiencies of the PAH-DNA adducts were found to be up to 100-fold less than expected and depended upon both the adduct and adduct levels (lower levels being less efficiently detected). The presence of unmodified nucleotides resulted in a 1.5-fold lower labeling efficiency. Mixtures of selected PAH-DNA adducts did not affect the labeling efficiencies of each other. The data suggest that previous 32P-postlabeling assay studies for PAH-DNA adducts may have underestimated adduct levels due to variations in labeling efficiency. PMID- 8464381 TI - Mutagenic and lethal effects of halogenated methanes in the Ara test of Salmonella typhimurium: quantitative relationship with chemical reactivity. AB - The mutagenic and lethal effects of nine halogenated methanes (CCl4, carbon tetrachloride; CHCl3, chloroform; CH2Cl2, dichloromethane; CBr4, carbon tetrachloride; CHBr3, bromoform; CH2Br2, dibromomethane; CI4, carbon tetraiodide; CHI3, iodoform; and CH2I2, diiodomethane) have been investigated with the Ara forward-mutation assay of Salmonella typhimurium. Five substances (CH2Cl2, CBr4, CH2Br2, CHI3 and CH2I2) gave clear mutagenic responses. In all these cases the mutagenicity diminished in the presence of mammalian metabolic activation (S9 mixture). Two halomethanes (CCl4 and CHBr3) were classified as 'questionable' mutagens since they did not double the spontaneous value although a dose-response curve was obtained. All halomethanes tested exerted a lethal effect. A high concordance was found between lethality and chemical reactivity, as expected from the type and number of halogenated substituents. Compounds with equal numbers of substituents were lethal in the order I > Br > Cl. Additionally, the lethality of compounds with identical halogen substituents increased by successive halogenations. No such concordances were observed with respect to mutagenic activity. Structure-activity quantitative relationships were investigated by using the previously reported values of the polarographic half-wave reduction potential (-E1/2), a physicochemical parameter related to the energy required to put an electron into the lowest unoccupied molecular orbital. The lethality, quantified as LD37, correlated highly with the -E1/2 values for the nine halogenated compounds (r = -0.955 P < 0.001). These data suggest that halomethanes which are reduced easily will induce higher lethality than those with low reduction potential, in agreement with the predicted effects on lipid peroxidation and hepatotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464382 TI - Spontaneous mutagenesis in Escherichia coli harbouring plasmid pKM101: DNA sequence analysis of forward lacI- mutations. AB - To investigate the influence of plasmid pKM101 on spontaneous mutagenesis, 198 lacI- mutations generated in Escherichia coli harbouring pKM101 were characterized at the DNA sequence level. pKM101 by itself did not enhance the lacI- forward mutation frequency. In general, the resultant distribution of mutation highlights particular sequences at which a variety of mutational events repeatedly occur, including 5'-(G/C)TGG-3', 5'-CCAGG-3', 5'-GATC-3' and 5'-TCGCG 3' sequences. Specifically, the distribution of mutation within base substitution and deletion classes distinguishes the pKM101 spectrum from the wild-type distribution (i.e. absence of pKM101). An even distribution amongst base substitutions was observed which corresponds to a 2.9- to 6.3-fold increase in occurrence of low frequency events (A-->G,T,C; G-->C); high frequency events in the wild-type distribution (G-->A,T) were not influenced by the presence of pKM101. One complex event was recovered which was comprised of two base substitutions separated by 4 bp. An 11-fold increase in small deletion events (3 6 bp) was also observed. The observed pKM101 spectrum does not closely resemble the mutational consequences of SOS induction in the absence of mutagenic treatment (recA441 spectrum) but does return a distribution like that obtained in E. coli deficient in polymerase I activity (polA1 spectrum). PMID- 8464383 TI - Radiosensitive Chinese hamster irs2 cells show enhanced chromosomal sensitivity to ionizing radiation and restriction endonuclease induced blunt-ended double strand breaks. AB - The Chinese hamster irs2 cell line shows cellular hypersensitivity to ionizing radiation although the induction and repair of double-strand breaks (dsb) in bulk DNA is normal. Here we report that irs2 shows chromosomal hypersensitivity to ionizing radiation and the restriction endonuclease PvuII. The ratio of induced chromosomal aberrations in irs2 versus V79 was similar to that for survival (factor of between 2 and 4). PvuII was administered during cell poration with the bacterial toxin streptolysin O. We also report that when streptolysin O porated irs2 and V79 cells were treated with PvuII, and dsb assayed by neutral filter elution, equivalent numbers of dsb were induced in the two lines as a function of time following treatment. Our data show that irs2 has a DNA damage processing defect that leads to enhanced conversion of blunt-ended dsb into visible chromosomal damage. PMID- 8464384 TI - Determination of target nucleotides involved in 7-methoxy-2-nitro-naphtho[2,1 b]furan (R7000)-DNA adduct formation. AB - The characterization of target nucleotides involved in the binding to DNA of 7 methoxy-2-nitro-naphtho[2,1-b]furan (R7000), a very potent genotoxic nitrofuran derivative, was investigated. Since R7000 undergoes metabolic activation prior to interacting with DNA, plasmids containing AT-rich and GC-rich sequences were devised and treated by R7000 in bacterial cells presenting nitroreductase activity. The nucleotide modifications to these homogeneous fragments that resulted from R7000 treatment were analyzed using the 'postlabeling' method. A preferential binding to the GC segment was demonstrated. Using a modification of the Maxam-Gilbert sequencing technique, it was demonstrated that activated R7000 creates alkali-labile phosphodiester bonds at the positions of guanines. In addition, the analysis of DNA replication-blocking properties of R7000 lesions was performed using avian myeloblastosis virus (AMV) reverse transcriptase as DNA polymerase. The termination of DNA replication occurred preferentially at the sites of guanine residues in the template strand, indicating that one nucleotide was inserted opposite a lesion. All these results indicate that guanine residues are the preferential sites of formation of R7000-DNA adducts. PMID- 8464385 TI - A single-site mutation in the XPAC gene alters photoproduct recognition. AB - The XPAC (xeroderma pigmentosum group A complementing) gene, which is located on chromosome 9, carries a variety of point mutations in XP group A patients. We investigated the role of the XPAC gene product in excision repair by generating revertants of an XP group A cell line (XP12RO) that have increased resistance to ultraviolet light. One of these cell lines, XP129, can repair (6-4) pyrimidine pyrimidone photoproducts normally but has reduced repair of cyclobutane dimers, as in XP12RO. Sequence analysis of cDNA from the XPAC gene indicated that XP12RO contains a termination codon at amino acid position 207, resulting in a reduced amount of mRNA and no detectable protein. In the revertant XP129 line, this termination codon has been mutated further and now encodes glycine in one allele instead of the wild-type arginine. The mRNA level detected by allele-specific polymerase chain reaction amplification was greater for the reverted sequence than for the chain-terminating sequence. These observations indicated that a point mutation resulting in a mis-sense mutation in the XPAC gene and altered expression of the XPAC protein can alter the substrate specificity of the excision repair system, and imply that the XPAC gene product plays an important role in photoproduct recognition. PMID- 8464386 TI - Availability of the GENE-TOX database on the National Library of Medicine TOXNET system. PMID- 8464387 TI - [Aromatase inhibitor]. PMID- 8464388 TI - [Decubitus ulcer. Etiology, clinical picture, treatment and prevention]. PMID- 8464389 TI - [Intestinal side effects of antibiotics]. PMID- 8464390 TI - [Antibiotic therapy in general practice]. PMID- 8464391 TI - [In honor of Professor Dr. H. Goebell's 60th birthday]. PMID- 8464392 TI - [The terminal ileum as a co-regulator of cyclic interdigestive pancreatic secretion in man]. AB - Nutrients present in the ileum of humans can modulate endogenously stimulated pancreatic secretion. To determine whether cyclic interdigestive pancreatic secretion can also be influenced by nutrients in the ileum, six fasting volunteers were intubated with an oro-ileal multi-lumen tube for perfusing test and marker solutions, aspiration of duodenal contents and recording of motility. At the beginning of the interdigestive cycle, the ileum was perfused intermittently with solutions of carbohydrates, proteins or lipids in the physiological amounts observed in the ileum after a meal; saline solution was perfused as a control. After saline, protein and calcium perfusion, the expected periodic increase in chymotrypsin secretion was observed during phase II of the interdigestive cycle (p < 0.05 vs phase I). In contrast, carbohydrates and lipids inhibited the phase-II-associated increase in pancreatic secretion. These findings indicate that the ileum may be involved in the regulation of human interdigestive pancreatic secretion. PMID- 8464393 TI - [The synthetic somatostatin analog octreotide: effect on interdigestive pancreas secretion and gastrointestinal motility in man]. AB - The aim of the present study was to determine the effects of a therapeutical dose of the long-acting cyclic somatostatin analogue octreotide (SMS 201-995) on cyclical interdigestive small intestinal motor function and exocrine pancreatic secretion in humans. Five fasting healthy subjects swallowed a gastroduodenal multi-lumen tube assembly and received continuous infusions of saline and octreotide (720 ng/kg/hr) for at least one interdigestive motor cycle or two hours. Upper gastrointestinal motility was recorded continuously by standard manometry. Duodenal chymotrypsin outputs were measured at 15 minutes intervals using polyethylene glycol as a dilution marker. Octreotide significantly decreased the length of the interdigestive motor cycle to one third of the control period (p < 0.01). Phase II proportion was reduced to less than 5% of the cycle length (controls: 66%; p < 0.01). The propagation velocity of octreotide induced motor activity fronts was significantly slower compared with migrating motor complexes during the control period (controls: 6.8 +/- 0.4 cm/min, octreotide: 2.3 +/- 0.4 cm/min; p < 0.05). Overall duodenal chymotrypsin output was markedly inhibited by octreotide (5% of controls; p < 0.01). Moreover, during octreotide administration coupling between interdigestive motor activity and pancreatic exocrine enzyme secretion was disrupted. In conclusion short administration of a therapeutical dose of octreotide exerts similar effects on upper intestinal interdigestive human motor secretory parameters as naturally occurring molecular forms of somatostatin at pharmacological doses. PMID- 8464394 TI - [Effect of the prostaglandin E2 analog nocloprost on motility and acid clearance of the tubular esophagus in man]. AB - The effects of the E2 prostaglandin nocloprost (9b-chloro-16,16-dimethyl prostaglandin E2) on esophageal motility and acid clearance were evaluated in a double-blind placebo controlled study in six healthy volunteers. Motility of the tubular esophagus was measured by means of a low compliance perfusion system (four channels, recording ports 10 cm apart, the distal localized in the stomach). After eight hours fasting and a 60-minutes baseline measurement (with standardized swallowing of 5 cc water every three minutes) the volunteers swallowed on two separate days in randomized order either 200 micrograms nocloprost (solved in 50 cc water) or placebo. Then the motility of the tubular esophagus was assessed for another 60-minutes during standardized swallowing. Thereafter, the motility probe was removed and a pH-electrode placed 10 cm above the lower esophageal sphincter. In order to assess the esophageal clearance, four times 5 cc of 0.1 N HCl were infused into the esophagus 10 cm above the electrode and the time between the infusion of HCl and the increase of the pH above pH 4.0 measured. RESULTS: In five out of six volunteers the duration of esophageal contractions were decreased after administration of nocloprost as compared to placebo (6.23 +/- 1.2 vs. 5.80 +/- 1.1 seconds, p = 0.07). In contrast, neither propagation velocity, nor amplitude of contraction or acid clearance were significantly affected by nocloprost. CONCLUSIONS: These findings suggest that in healthy volunteers nocloprost changes the pattern of esophageal contractions (duration) without affecting amplitude, velocity of propagation or acid clearance. PMID- 8464395 TI - [Postprandial serum bile acid level and 75SeHCAT retention in diagnosis of bile acid malabsorption syndrome. A comparative study]. AB - Postprandial serum bile acids (expressed as integrated bile acid response [IR]) after a standardized test meal were compared with 75SeHCAT retention, measured in a whole body counter, in healthy controls (n = 20), in 44 patients with ileal disease or resection and in 23 patients with colitis without ileal involvement. In the controls the IR after 180 min was 736 +/- 186 mumol x min x 1(-1) (mean +/ standard deviation), the 75SeHCAT retention 31 +/- 9%. 80% of the patients with ileal disease or resection had a decreased 75SeHCAT retention, indicating bile acid malabsorption, but only 59% had a diminished IR. One of the 23 patients with colitis and radiologically normal ileum had a decreased 75SeHCAT retention but a normal IR, reflecting a dysfunction of the morphologically normal ileum. The characteristics of the two tests are: 75SeHCAT retention test: sensitivity 80%, specificity 98%, accuracy 89%; postprandial serum bile acids: sensitivity 64%, specificity 74%, accuracy 69%. With respect to chronic inflammatory bowel disease the positive predictive value of the 75SeHCAT retention test is 1.0%, for postprandial serum bile acids 0.1%, whereas the negative predictive values amount to 99% for both tests. Thus 75SeHCAT retention is more reliable in detecting bile acid malabsorption than the determination of postprandial serum bile acids, although both tests are not usefull for screening the population for ileal disease. PMID- 8464396 TI - [Differential diagnosis of chronic diarrhea: indicative findings of factitious diarrhea (Munchausen syndrome) with bisacodyl by the pathologist]. PMID- 8464397 TI - [To what extent are sedation and monitoring in endoscopic examinations of the gastrointestinal tract necessary? A contribution to current discussions]. PMID- 8464398 TI - [Differential effects of ethanol and alcoholic beverages on secretion of stomach acid and gastrin liberation in man--current status of research]. PMID- 8464399 TI - [Smoking and ovulation inhibitor in inflammatory bowel diseases]. AB - In a case-control study the effects of smoking and the use of oral contraceptives were examined in 83 patients with Crohn's disease and 37 patients with ulcerative colitis in comparison with members of the general population who served as controls. After controlling for oral contraceptives, smokers were found to have a significantly elevated relative risk of contracting Crohn's disease of 3.0 (1.3 to 6.8). Patients on oral contraceptives for more than three years had an elevated risk for Crohn's disease of 4.3 (1.3 to 14.4); this elevated risk was, however, found only in the non-smoking group. In the case of ulcerative colitis, the relative risk in smokers was significantly lower (0.21 [0.04 to 0.91]) than in non-smokers. The use of oral contraceptives does not represent a risk factor for ulcerative colitis. While smoking has been established as a risk factor in the development of inflammatory bowel disease, the role of oral contraceptives in the aetiology of this condition remains unclear. PMID- 8464400 TI - [Benign recurrent intrahepatic cholestasis: a rare cause of juvenile jaundice]. PMID- 8464401 TI - [Y1 receptors mediate inhibitory and stimulatory effects of peptide YY in isolated small intestine and large intestine muscles of the rabbit]. AB - Peptide YY has been shown to have stimulatory and inhibitory effects on gastrointestinal motility. However, the receptors mediating these effects are unknown. To determine if specific YY receptor agonists can mediate the effects on gastrointestinal motility we studied the effects of peptide YY (PYY), of Pro34PYY, a selective Y1 agonist, and of PYY 3-36, a selective Y2 agonist, on the motility in isolated smooth muscle strips from rabbit small and large intestine. In strips from distal colon, PYY stimulated spontaneous motility whereas it inhibited spontaneous contractions in circular strips from distal ileum. In distal circular colon maximal inotropic response (10.1 +/- 2.1% of a maximal response to carbachol 10(-5) M) was found at PYY 10(-8) M; (ED50 3.1 +/- 1.2 x 10(-9) M). In distal circular ileum maximal inhibition (by 39 +/- 20% of basal motility index) was found at 10(-7) M; (ID50 6.2 +/- 1.4 x 10(-9) M). PYY caused a dose-dependent inhibition of the on-contraction induced by electrical field stimulation. This inhibition could not be reversed by alpha- or beta-adrenergic blockade. PYY had no influence on the inotropic response evoked by carbachol. Both the stimulatory effect of PYY observed in distal colon and the inhibitory effect in distal ileum could be reproduced by the Y1 agonist Pro34PYY, but not by the Y2 agonist PYY 3-36. In distal circular colon the maximal inotropic response evoked by the Y1 agonist was 10 +/- 1.4%; (ED50 1.2 +/- 0.5 x 10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464402 TI - Bacillus subtilis sporulation: regulation of gene expression and control of morphogenesis. AB - Bacillus subtilis sporulation is an adaptive response to nutritional stress and involves the differential development of two cells. In the last 10 years or so, virtually all of the regulatory genes controlling sporulation, and many genes directing the structural and morphological changes that accompany sporulation, have been cloned and characterized. This review describes our current knowledge of the program of gene expression during sporulation and summarizes what is known about the functions of the genes that determine the specialized biochemical and morphological properties of sporulating cells. Most steps in the genetic program are controlled by transcription factors that have been characterized in vitro. Two sporulation-specific sigma factors, sigma E and sigma F, appear to segregate at septation, effectively determining the differential development of the mother cell and prespore. Later, each sigma is replaced by a second cell-specific sigma factor, sigma K in the mother cell and sigma G in the prespore. The synthesis of each sigma factor is tightly regulated at both the transcriptional and posttranslational levels. Usually this regulation involves an intercellular interaction that coordinates the developmental programmes of the two cells. At least two other transcription factors fine tune the timing and levels of expression of genes in the sigma E and sigma K regulons. The controlled synthesis of the sigma factors and other transcription factors leads to a spatially and temporally ordered program of gene expression. The gene products made during each successive stage of sporulation help to bring about a sequence of gross morphological changes and biochemical adaptations. The formation of the asymmetric spore septum, engulfment of the prespore by the mother cell, and formation of the spore core, cortex, and coat are described. The importance of these structures in the development of the resistance, dormancy, and germination properties of the spore is assessed. PMID- 8464404 TI - Ether polar lipids of methanogenic bacteria: structures, comparative aspects, and biosyntheses. AB - Complete structures of nearly 40 ether polar lipids from seven species of methanogens have been elucidated during the past 10 years. Three kinds of variations of core lipids, macrocyclic archaeol and two hydroxyarchaeols, were identified, in addition to the usual archaeol and caldarchaeol (for the nomenclature of archaeal [archaebacterial] ether lipids, see the text). Polar head groups of methanogen phospholipids include ethanolamine, serine, inositol, N acetylglucosamine, dimethyl- and trimethylaminopentanetetrol, and glucosaminylinositol. Glucose is the sole hexose moiety of glycolipids in most methanogens, and galactose and mannose have been found in a few species. Methanogen lipids are characterized by their diversity in phosphate-containing polar head groups and core lipids, which in turn can be used for chemotaxonomy of methanogens. This was shown by preliminary simplified analyses of lipid component residues. Core lipid analysis by high-pressure liquid chromatography provides a method of determining the methanogenic biomass in natural samples. There has been significant progress in the biosynthetic studies of methanogen lipids in recent years. In vivo incorporation experiments have led to delineation of the outline of the synthetic route of the diphytanylglycerol ether core. The mechanisms of biosynthesis of tetraether lipids and various polar lipids, and cell-free systems of either lipid synthesis, however, remain to be elucidated. The significance and the origin of archaeal ether lipids is discussed in terms of the lipid composition of bacteria living in a wide variety of environments, the oxygen requirement for biosynthesis of hydrocarbon chains, and the physicochemical properties and functions of lipids as membrane constituents. PMID- 8464403 TI - Protein secretion in Bacillus species. AB - Bacilli secrete numerous proteins into the environment. Many of the secretory proteins, their export signals, and their processing steps during secretion have been characterized in detail. In contrast, the molecular mechanisms of protein secretion have been relatively poorly characterized. However, several components of the protein secretion machinery have been identified and cloned recently, which is likely to lead to rapid expansion of the knowledge of the protein secretion mechanism in Bacillus species. Comparison of the presently known export components of Bacillus species with those of Escherichia coli suggests that the mechanism of protein translocation across the cytoplasmic membrane is conserved among gram-negative and gram-positive bacteria differences are found in steps preceding and following the translocation process. Many of the secretory proteins of bacilli are produced industrially, but several problems have been encountered in the production of Bacillus heterologous secretory proteins. In the final section we discuss these problems and point out some possibilities to overcome them. PMID- 8464408 TI - [Postoperative recurrence form of Crohn's disease: comparison between perforating and non perforating types]. AB - Postoperative recurrence rate and recurrence form were analyzed in two clinical forms of Crohn's disease at primary resection, one of which was perforating and the other was non perforating. Forty four patients with Crohn's disease were included in this study, 18 of them were perforating type and 26 were non perforating type. Crude recurrence rates were 39% (7/18 cases) in perforating type group and 54% (14/26 cases) in non perforating type group, which were not significantly different. Cumulative recurrence rates 5 years after initial operation were 58% in perforating type group and 47% in non perforating group without statistically significance. The recurrence form was perforating type more frequently in perforating type group (86%) than non perforating group at primary resection (29%) with statistically significance (p = 0.013). Postoperative recurrence form had a tendency to be similar to the form at primary resection. It was suggested from this study that Crohn's disease had two different disease entities; perforating and non perforating types and that postoperative recurrence should be examined carefully from the view of primary resection. PMID- 8464407 TI - [Experimental studies on the development of residual stomach cancer--comparison of Billroth I and Billroth II]. AB - The effects of duodenogastric reflex on the development of residual stomach cancer and cell proliferation kinetics were investigated in Wistar rats. Billroth II resection (B-II group) was performed on 24 rats and Billroth I resection (B-I group) was performed on 22 rats. The incidence of cancer in the B-II group was 20.8%, though no cancer was noted in the B-I group. The incidences of the pseudopyloric gland, dilated gland and gastritis cystica profunda in the B-II group were significantly higher than those in the B-I group. The degree of mucosal atrophy was greater in the B-II group than in the B-I group. The stomal area in the B-II group had expansion of proliferative zone as well as increased S phase duration and turn over time, compared with those in the B-I group. The sequence of histological and proliferative events associated with duodenogastric reflux suggests that the residual stomach in the B-II group is susceptible to the development of cancer. PMID- 8464409 TI - [Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA102: experience of 20 cases]. AB - The monoclonal antibody CEA 102 against carcinoembryonic antigen was produced by immunization with purified CEA, and used as a radiotracer for the imaging of colorectal cancer. CEA102 was labeled with 131I by the chloramine-T or the Iodogen method, and administered i.v. to 20 patients with liver metastases, local recurrences, and/or primary tumors. Planar scintigraphy was performed during 5 or 6 postinfusion days. Hypersensitivity reactions such as fever and chill occurred in 4 patients, but no side effects were noted after endotoxin was excluded. Overall sensitivity was 71.4% (primary tumor 4/4, liver metastasis 5/6, lymph node metastasis 1/1, local recurrence 5/10), and no false positive was observed. In the cases of local recurrences, this method was useful to distinguish postoperative fibrosis from local recurrence. These results revealed that radiolabeled CEA102 has a great potential in qualitative diagnosis of colorectal cancer. PMID- 8464410 TI - [Characterization of autologous-tumor specific cytotoxic T cells induced by means of butanol-extracted soluble antigen from T lymphocytes in colon cancer patients]. AB - Tumor-specific T lymphocytes (CTL) are proliferated in vitro to induce by a stimulation with butanol-extracted soluble antigen (CBE) and human recombinant interleukin-2 (IL-2) from peripheral lymphocytes of cancer patients. Peripheral blood T lymphocytes (PBL-T), tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNC) from patients with colon cancer were stimulated in vitro with CBE and IL-2. Single stimulation with CBE (1 x 10(-3) micrograms/ml) also activated the proliferative response of the PBL-T (p < 0.01). On the other hand, high-dose (0.25-2 micrograms/ml) significantly inhibited the proliferation of the PBL-T that had been stimulated with 20U/ml IL-2 (p < 0.001). The IL-2 receptor expression of PBL-T, TIL and LNC was also activated with low-dose CBE and IL-2. The surface markers of stimulated lymphocytes responded anti-CD3 and CD8 monoclonal antibodies, but some TIL and LNC displayed CD3 and CD4 phenotype. The lymphocytes responding anti-CD8 monoclonal antibody possessed the cytotoxic activity against autologous tumor cells, but not the lymphocytes responding anti CD4 monoclonal antibody. The results suggested that low-dose CBE and IL-2 augment the IL-2 receptor expression of T lymphocytes, thereby the proliferation of the antigen specific cytotoxic T cells. PMID- 8464411 TI - [Phenotypic and functional analyses of cells infiltrating rat hepatic allograft]. AB - In order to elucidate the immunological characteristics of rat liver transplantation, graft infiltrating cells (GIC) were isolated from rat hepatic allografts, and phenotypic and functional analyses were performed. Long-surviving combination (Lewis engrafted BN liver, MST = 166.8 +/- 28.1 days, n = 10) and acutely-rejected combination (Lewis engrafted DA liver, MST = 9.6 +/- 0.3 days, n = 6) were compared. Relative proportions of all T cells and activated T cells assessed by flow cytometry were significantly higher in Lewis recipients of acutely-rejected combination than in those of long-surviving combination on day 6 after transplantation. Phenotypic analyses of GIC on days 6, 14, and 45 after transplantation in Lewis hosts of long-surviving combination were assessed. All T cells, OX-8 positive cells (Tc/s, NK), and OX-39 positive (IL-2 receptor) cells showed peak levels on day 6 and decreased on day 45. Cytotoxic activity of GIC toward donor lymphocytes on day 6 was stronger in host of acutely-rejected combination (18.9 +/- 4.0%, E/T = 50) than in that of long-surviving combination (5.3 +/- 2.8%). On the other hand, NK activity in Lewis host of long-surviving combination was high (17.5 +/- 3.0%, E/T = 100) on day 6 after transplantation. These results demonstrate that some immunosuppressive mechanism is present already on day 6 after transplantation, and that infiltration or activation of cytotoxic T cells is inhibited in long-surviving combination of rat hepatic allografts. PMID- 8464412 TI - [Prognostic judgment of fulminant hepatitis by measurement of hepatosplenic volume ratio by computed tomography]. AB - The liver and spleen volume ratio (S/L ratio) was estimated with X-ray computed tomography and evaluated by comparison with the prognosis in 10 patients with fulminant hepatitis. S/L ratio of control group (n = 10) was 0.122 +/- 0.026 (mean +/- SD), that of the alive group with fulminant hepatitis (n = 5) was 0.112 +/- 0.021, and that of the dead group (n = 5) was 0.308 +/- 0.136. There is a significant difference between S/L ratio of control group and that of the dead group with fulminant hepatitis. The rise of S/L ratio on the patients with fulminant hepatitis reflects the liver atrophy or splenomegaly and the prognosis was poor. The prognosis of the patients with fulminant hepatitis, whose S/L ratio indicated the near value of control group, was good. The measurement of S/L ratio by computed tomography was considered to be useful to evaluate the prognosis of fulminant hepatitis. PMID- 8464413 TI - [Hemodynamics and treatment based on endoscopic classification of esophago gastric varices]. AB - The relationship between endoscopic findings and hemodynamics was studied in 262 patients. The endoscopic findings were classified into 3 groups; 1) Type 1: case with esophageal varices. 2) Type 2: case with esophago-cardiac varices. 3) Type 3: case with fundic varices. The hemodynamics were examined using late phase venography after conventional abdominal angiography. The blood vessels of type 1 resembled those of type 2, and 72% of the cardiac varices were connected with esophageal varices. On the other hand, the blood vessels of type 3 were completely different from those of type 1 and type 2, and 84% of the fundic varices were connected with large gastro-renal shunts. From these results, I have been applying endoscopic in injection sclerotherapy for types 1 and 2, and Hassab's operation for type 3. The rates of hemostasis were 100%, 93% and 100% in types 1, 2 and 3, respectively. The rates of disappearance of the varices after treatment were 78.7%, 87% and 100% in types 1, 2 and 3, respectively. It is concluded that good therapeutic results can be obtained when an appropriate therapeutic method is selected. Treatment should be based on the hemodynamics associated with the endoscopic findings of esophago-gastric varices. PMID- 8464406 TI - Meningococcal lipopolysaccharides: virulence factor and potential vaccine component. AB - Lipopolysaccharides (LPS) are surface components of the outer membrane of Neisseria meningitidis. Today, 12 different types of meningococcal LPS (immunotypes) are known, of which 3 are prevalent in the western world. The differences between these immunotypes are in the oligosaccharide part of the LPS molecule and consist of small differences in the oligosaccharide structure, the amount and location of phosphoethanolamine groups, and the degree of O acetylation of individual monosaccharides. Although the differences between the various immunotypes are small, they have a profound influence on the immunochemical and immunological properties of these molecules. Furthermore, each individual strain synthesizes a number of different LPS molecules. The expression of the various components (protective epitopes) is influenced by growth conditions and growth phase. Meningococci can endogenously sialyate their LPS, which constitutes one of the mechanisms by which N. meningitidis can evade the response of the human host. Meningococcal LPS play a key role in the induction of septic shock and can probably enhance the invasiveness of meningococcal strains and shield protective epitopes. Therefore, incorporation of (detoxified) LPS or oligosaccharide components derived therefrom might be very beneficial for the efficacy of a vaccine against group B meningococci. An overview of the development of vaccines against group B meningococci is given, and the status and potential of meningococcal LPS-derived (synthetic) oligosaccharide-protein conjugate vaccines are discussed. PMID- 8464414 TI - [The growth activity and DNA ploidy in anaplastic carcinoma transplanted to nude mice]. AB - Recently, nuclear DNA contents of various human tumors were studied, and DNA aneuploidy was thought to have prognostic significance in many kinds of malignant tumors. Although the same significance was reported in thyroid carcinoma, the anaplastic thyroid carcinoma which is one of the most aggressive tumor in human malignant neoplasms, not always shows DNA aneuploidy. Therefore, using 3 xenografts established from 3 patients with anaplastic thyroid carcinomas, we investigated their growth activity, DNA ploidy and chromosome abnormalities. Two of these xenografts grew relatively fast in nude mice showing diploid or near diploid state in a flow cytometric study, and also, showed many structural abnormalities in chromosome analysis by the G-banding technique. The remaining one xenograft showed slower growth and aneuploidy, and had extensive numerical but less structural variability in its chromosomal constitution. These results indicate that some tumors showed DNA diploidy and have structural chromosome abnormalities and also suggest that the prognostic value of quantitative DNA measurement is limited in such tumors. PMID- 8464415 TI - [Ogilvie's syndrome in pregnancy--a case report]. AB - A 23-year-old female in the 28th week of pregnancy was admitted with an acute abdominal distension. The plain X-ray films showed a marked gaseous dilatation of the colon from the cecum to the splenic flexure. A tube colostomy was performed. Her postoperative course was uneventful and she improved progressively. Her pregnancy and delivery elapsed uneventfully there after. After the delivery she again complained of marked abdominal distension. The colonoscopic decompression in combination with the administration of Cisapride was successfully accomplished. Ogilvie's syndrome is characterized by an unobstructed colon which progresses to marked dilatation. When the colonic diameter becomes 12cm or more, surgical decompression should be recommended to avoid the hazard of spontaneous rupture. This is the first reported case of Ogilvie's syndrome in pregnancy in Japan. PMID- 8464416 TI - [Single-stage management of postoperative sternal wound infection using a pectoral musculocutaneous flap]. AB - Two patients with postoperative sternal wound infection were successfully treated by a pectral musculocutaneous flap. A single-stage procedure of debridement and immediate closure with a pectral musculocutaneous flap can eliminate irrigation, open wound management, or reoperation for closure. Therefore, this method is very safe, simple, and effective for the management of sternal wound infections. PMID- 8464417 TI - [Surgical treatment for true aneurysm of the deep femoral artery, and a review of literatures in Japan]. AB - A true aneurysm of the deep femoral artery is very rare among peripheral aneurysms because of its anatomical position and characteristics of wall tissue. An early operation is mandatory because it has a tendency to become a large size and to rupture. During the last eight years, we experienced two cases. One ruptured case underwent only resection of aneurysm and another case received an additional reconstruction of deep femoral artery using saphenous vein graft. Both of them are doing well postoperatively. In this paper, a review of 24 cases including these two in Japanese literature was discussed. PMID- 8464418 TI - [Changes of the number of FdUMP binding sites of thymidylate synthase and folate pools in human colorectal carcinomas following the administration of tegafur and uracil: preliminary report]. PMID- 8464419 TI - [Glucose intolerance in patients with oxyhyperglycemia after subtotal gastrectomy -study with IV GTT--preliminary report]. PMID- 8464420 TI - [Orthotopically implanted human colon carcinoma xenografts can metastasize to liver via hematogenous spread: preliminary report]. PMID- 8464421 TI - [Morphological alterations in the hepatocytes of tumor-bearing, cachectic rats: preliminary report]. PMID- 8464422 TI - [A technique for studying the periportal (zone 1) hepatocytes metabolism using a new liver perfusion method: preliminary report]. PMID- 8464423 TI - [A bioartificial parathyroid: preliminary report]. PMID- 8464424 TI - [Specificity and biodistribution of human monoclonal antibody 4G12 (human IgM) to esophageal carcinoma: preliminary report]. PMID- 8464425 TI - [Postoperative hypophosphatemia in patients with cancer of the thoracic esophagus]. AB - Postoperative phosphate dynamics were studied in 30 patients who underwent radical surgery for thoracic esophageal cancer and who were postoperatively nourished by total parenteral nutrition. There was a significant fall in the serum phosphate level on the 2nd and 3rd postoperative days in all patients. Postoperative hypophosphatemia was due to an increase in urinary phosphate excretion which was indicated by the fall in TRP% and TmPO4/GFR. A highly significant positive correlation was observed between the increase in urinary phosphate loss and the enhanced secretion of parathyroid hormone which was possibly triggered by surgical stress, a decrease in the serum level of calcium, the action of phosphate buffer or diuretics. All the patients except for those with postoperative pulmonary complications responded to the drop in serum phosphate by renal conservation of phosphate. A slight decrease in the serum level of phosphate was also found on the 6th postoperative day in most patients who were receiving parenteral hyperalimentation. The second fall in phosphate was due to transcellular shifts of phosphate. It is concluded that patients with postoperative pulmonary complications develop severe hypophosphatemia which should be prevented by replacement therapy with phosphate in the immediate postoperative period. PMID- 8464426 TI - Rapid isolation and biochemical characterization of rat C1 and C1q. AB - Using a human IgG-Sepharose column to which rabbit anti-human IgG was bound (rabbit anti-human/human IgG-Sepharose), human and rat C1 or C1q were isolated from serum in a single step, and the C1q further purified to homogeneity by FPLC. This procedure allowed the rapid isolation of haemolytically active C1 or C1q, with a yield equal to or greater than published methods. The availability of human and rat C1q allowed comparison of the two molecules, revealing differences in their mobility on SDS-PAGE as well as on agarose gel electrophoresis. Amino terminal sequence analysis demonstrated greater than 78% residue identity between rat C1q A, B and C chains and the published human and mouse sequences. Similar amino acid compositions suggest that the homology extends throughout the molecules. In addition to the major A:B and C:C dimer bands, rat, unlike human C1q, contained minor dimer species. These may reflect heterogeneity in glycosylation and or lysine and proline hydroxylation. PMID- 8464427 TI - Differential expression of Fc gamma RIIA, Fc gamma RIIB and Fc gamma RIIC in hematopoietic cells: analysis of transcripts. AB - Fc gamma receptors (Fc gamma R) are glycoproteins that function in the immune response through their ability to bind the Fc portion of immunoglobulin G. Of the three human Fc gamma R classes, Fc gamma RII is most widely distributed among hematopoietic cells and is the only Fc gamma R class present on platelets and megakaryocytes. There are three different genes coding for Fc gamma RII: Fc gamma RIIA, Fc gamma RIIB and Fc gamma RIIC. Alternative splicing of at least two of these genes results in the production of multiple transcripts. Combining Northern blot analysis with reverse transcription-PCR, we analyzed steady state levels of Fc gamma RII mRNA in the megakaryocytic, myeloid and lymphoid lineages. We determined that megakaryocytic cells predominantly contain Fc gamma RIIA mRNA; Fc gamma RIIA transcripts with and without the transmembrane exon (Fc gamma RIIa1 and Fc gamma RIIa2, respectively) are present in comparable amounts. In contrast, B lymphocytes do not express Fc gamma RIIA mRNAs, but do contain both Fc gamma RIIB transcripts, Fc gamma RIIb1 and Fc gamma RIIb2, as well as the Fc gamma RIIC transcript, Fc gamma RIIc. Myelomonocytic cells contain mRNAs from all three Fc gamma RII genes, predominantly the Fc gamma RIIa1 transcript, both Fc gamma RIIb1 and Fc gamma RIIb2 transcripts and Fc gamma RIIc. Lineage-specific expression of the Fc gamma RII genes implies both differential regulation of expression and differential function in diverse cells. PMID- 8464428 TI - Comparison of nucleotide sequences from upstream of the DQ52 gene to the S mu region of immunoglobulin heavy-chain gene loci between Suncus murinus, mouse and human. AB - The nucleotide sequence of a 4621 base pair fragment of DNA, from a position upstream of DSQ52 to the S mu region within immunoglobulin heavy-chain gene loci of Suncus murinus was determined. The sequence contained one D gene, three JH genes and an enhancer. Suncus murinus is an insectivore and is one of the most primitive mammals. Both primates and rodents are thought to have originated from insectivores and to have evolved separately. We also determined the nucleotide sequence of a region between human JH genes and the enhancer which has not previously been reported. Thus, the sequences of the entire region from each of the three species, Suncus murinus, human and mouse are now available. Comparison of the nucleotide sequence of this region between these three species indicated that D and JH genes, consisting of coding and signal regions, are highly conserved. Moreover, although extensive sequence homology in the region between JH and S mu was observed between mouse and human, only core portions of the enhancer region of Suncus murinus exhibited homology to those of mouse and human. Sequence conservation of JH genes in Suncus murinus, mouse and human was observed not only at the amino-acid level, but also at the nucleotide level, including the third letters of the codons. It is suggested that JH genes may play a role in the metabolism of the DNA and/or RNA. PMID- 8464429 TI - Abnormal kappa B-binding protein in the cytoplasm of a plasmacytoma cell line that lacks nuclear expression of NF-kappa B. AB - The transcription factor NF-kappa B appears to play an important role in immunoglobulin gene expression and lymphokine production, and may play a role in primary B cell activation. Constitutive nuclear expression of NF-kappa B has been found in all mature B cell lines with the notable exception of the murine plasmacytoma, S107. We report herein that S107 cells express cytoplasmic kappa B binding material detected by electrophoretic mobility shift assay that by several criteria represents authentic NF-kappa B. Despite the presence of cytoplasmic NF kappa B, several stimuli known to induce nuclear translocation of NF-kappa B failed to do so in S107 cells, including: the PKC agonist, PMA; the protein synthesis inhibitor, cycloheximide; and LPS. Transfection of S107 cells with a kappa B-CAT reporter gene construct confirmed the absence of functional activity. Importantly, a global failure of nuclear transcription factor expression was ruled out by the ability of PMA to induce nuclear expression of another trans acting factor, AP-1. Thus, rather than lacking NF-kappa B altogether, S107 cells manifest disordered regulation of NF-kappa B in which cytoplasmic material is incapable of translocation to the nucleus. While Northern analysis failed to reveal a gross defect in the mRNA coding for the DNA binding subunit of NF-kappa B, UV-photo-cross-linking followed by denaturing gel electrophoresis demonstrated the presence of a cytoplasmic kappa B-binding protein of abnormally elevated molecular size. This finding suggests that the abnormal regulation of NF-kappa B in S107 cells is associated with the appearance of an unusual kappa B-binding molecule. PMID- 8464430 TI - Evaluation of structure-antigenicity relationship of peptides from human immunodeficiency virus type 1 (HIV-1) p18 protein by circular dichroism. AB - The antigenicity of Human Immunodeficiency Virus type 1 (HIV-1) matrix p18 protein was evaluated by analyzing the specificity of anti-p18 antibodies elicited either in HIV-1 infected humans, or in HIV-1 infected or immunized chimpanzees, against a panel of long and short overlapping synthetic peptides [from 12 to 46 amino acid (aa) residues] covering the entire sequence of p18. The relationship between peptide structure and antigenicity was further investigated by probing the secondary structures of the peptides by circular dichroism. The results obtained clearly showed the immunodominance of the N-terminal region mimicked by peptide P1 (aa 2-45), which reacted with 52 and 100% of human and chimpanzee anti-p18 sera, respectively. In contrast smaller 15 aa long peptides C1, C2, C3, C4 and P3 which cover the entire sequence of immunodominant peptide P1, showed only weak or no reactivity. In contrast to widely accepted hypotheses, circular dichroism analysis of both small and large peptides secondary structures did not show any obvious correlation between antigenicity and the ability of peptides to adopt an ordered conformation. PMID- 8464431 TI - The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. AB - BACKGROUND: A diet low in saturated fat and cholesterol is the standard initial treatment for hypercholesterolemia. However, little quantitative information is available about the efficacy of dietary therapy in clinical practice or about the combined effects of diet and drug therapy. METHODS: One hundred eleven outpatients with moderate hypercholesterolemia were treated at five lipid clinics with the National Cholesterol Education Program Step 2 diet (which is low in fat and cholesterol) and lovastatin (20 mg once daily), both alone and together. A diet high in fat and cholesterol and a placebo identical in appearance to the lovastatin were used as the respective controls. Each of the 97 patients completing the study (58 men and 39 women) underwent four consecutive nine-week periods of treatment according to a randomized, balanced design: a high-fat diet placebo period, a low-fat diet-placebo period, a high-fat diet-lovastatin period, and a low-fat diet-lovastatin period. RESULTS: The level of low-density lipoprotein (LDL) cholesterol was a mean of 5 percent (95 percent confidence interval, 3 to 7 percent) lower during the low-fat diet than during the high-fat diet (P < 0.001). With lovastatin therapy as compared with placebo, the reduction was 27 percent. Together, the low-fat diet and lovastatin led to a mean reduction of 32 percent in the level of LDL cholesterol. The level of high-density lipoprotein (HDL) cholesterol fell by 6 percent (95 percent confidence interval, 4 to 8 percent) during the low-fat diet (P < 0.001) and rose by 4 percent during treatment with lovastatin (P < 0.001). The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin (P < 0.001), but not by the low-fat diet. CONCLUSIONS: The effects of the low-fat-low-cholesterol diet and lovastatin on lipoprotein levels were independent and additive. However, the reduction in LDL cholesterol produced by the diet was small, and its benefit was possibly offset by the accompanying reduction in the level of HDL cholesterol. PMID- 8464432 TI - Plasma triglyceride level and mortality from coronary heart disease. AB - BACKGROUND: Whether the plasma triglyceride level is a risk factor for coronary heart disease has been controversial, and evaluation of the triglyceride level as a risk factor is fraught with methodologic difficulties. METHODS: We studied the association between plasma triglyceride levels and the 12-year incidence of death from coronary heart disease in 10 North American populations participating in the Lipid Research Clinics Follow-up Study, while adjusting for the potential confounding effects of other risk factors for cardiovascular disease, including the level of high-density lipoprotein (HDL) cholesterol. All analyses were sex specific, and separate analyses were performed in high and low strata of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, fasting plasma glucose, and age. RESULTS: The rates of coronary death in both men and women increased with the triglyceride level. In Cox proportional-hazards models adjusted for age, in which the natural log of the triglyceride levels was used to give a normal distribution, the relative risk per natural-log unit of triglyceride (e.g., a triglyceride level of 150 mg per deciliter vs. a level of 55 mg per deciliter) was 1.54 (95 percent confidence interval, 1.19 to 1.98; P < 0.001) in men and 1.88 (95 percent confidence interval, 1.19 to 2.98; P < 0.007) in women. After an adjustment for potential covariates, however, these relative risks were not statistically significant. Analyses based on lipoprotein cholesterol levels revealed a positive association between the triglyceride level and coronary mortality in the lower stratum of both HDL and LDL cholesterol, but not in the higher stratum. Conversely, the HDL cholesterol level was unrelated to coronary mortality in the lower stratum of LDL cholesterol, but was strongly inversely associated with coronary death in the higher stratum of LDL cholesterol. The relative risk of coronary death associated with triglyceride level was higher at younger ages. The associations between the triglyceride level and coronary mortality in the lower HDL cholesterol, LDL cholesterol, and age strata were small and were further reduced by an adjustment for the fasting plasma glucose level. CONCLUSIONS: Overall, the plasma triglyceride level showed no independent association with coronary mortality. However, in subgroups of subjects with lower HDL and LDL cholesterol levels and in younger subjects, defined a priori, an association between the triglyceride level and coronary mortality was observed, although this association was small and was not statistically significant after an adjustment for the plasma glucose level. PMID- 8464433 TI - Combination chemotherapy in refractory immune thrombocytopenic purpura. AB - BACKGROUND: Chronic idiopathic thrombocytopenic purpura is a destructive thrombocytopenia caused by an autoantibody. About 80 percent of patients with chronic idiopathic thrombocytopenic purpura have remissions after either corticosteroid therapy or splenectomy. Some patients with resistant disease respond to other agents, but a substantial group are refractory to therapy. METHODS: We used combination chemotherapy to treat 10 patients with refractory immune thrombocytopenia. An average of 6.8 (range, 3 to 10) previous therapies, including corticosteroids and splenectomy, had been unsuccessful in these patients. The patients received from three to eight cycles of therapy consisting of cyclophosphamide and prednisone combined with either vincristine (one patient), vincristine and procarbazine (four patients), or etoposide (six patients, including one patient who received four cycles each containing procarbazine and etoposide). RESULTS: Among the 10 patients, 6 had complete responses (platelet count, > 180,000 per cubic millimeter); of these, 4 patients had responses that persisted for more than 11, 30, 54, or 126 months, 1 had a relapse 9 months after therapy but had a remission with further therapy and remained in remission for 48 months before dying of an unrelated illness, and another relapsed just before her fifth course of therapy. Two patients had partial responses (platelet count, > 50,000 per cubic millimeter); the platelet counts in one remained stable for more than nine months after the end of therapy, and the other patient relapsed. The remaining two patients had no response. Complete responses were associated with a disappearance or marked decrease in the level of platelet-associated autoantibody. CONCLUSIONS: Combination chemotherapy is beneficial in some patients in whom immune thrombocytopenia is refractory to corticosteroids and splenectomy. PMID- 8464434 TI - The occurrence of sleep-disordered breathing among middle-aged adults. AB - BACKGROUND: Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health. METHODS: A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep disordered breathing in this group using three cutoff points for the apnea hypopnea score (> or = 5, > or = 10, and > or = 15); we used logistic regression to investigate risk factors. RESULTS: The estimated prevalence of sleep disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for women and 24 percent for men. We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome (an apnea-hypopnea score of 5 or higher and daytime hypersomnolence). Male sex and obesity were strongly associated with the presence of sleep-disordered breathing. Habitual snorers, both men and women, tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher. CONCLUSIONS: The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women. Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence. PMID- 8464435 TI - Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. PMID- 8464436 TI - Immunization of adults. PMID- 8464437 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 17-1993. A 53-year-old woman who died after several years of a dementing illness with intermittent generalized seizures and abnormal movements of the extremities and head. PMID- 8464438 TI - Medicine at center stage. PMID- 8464405 TI - Pathogenesis of human immunodeficiency virus infection. AB - The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. PMID- 8464439 TI - Screening for lipid disorders under health system reform. PMID- 8464441 TI - Self-referral by physicians. PMID- 8464440 TI - Sleep apnea--a major public health problem. PMID- 8464442 TI - Self-referral by physicians. PMID- 8464443 TI - Self-referral by physicians. PMID- 8464444 TI - Increased costs and rates of use in the California workers' compensation system as a result of a self-referral by physicians. PMID- 8464445 TI - Increased costs and rates of use in the California workers' compensation system as a result of self-referral by physicians. PMID- 8464446 TI - "Self-referral"--what's at stake? PMID- 8464447 TI - "Self-referral"--what's at stake? PMID- 8464449 TI - "Self-referral"--what's at stake? PMID- 8464448 TI - "Self-referral"--what's at stake? PMID- 8464450 TI - Snoring and sleep-related breathing abnormality during partial sleep deprivation. PMID- 8464451 TI - Age and the cardiovascular system. PMID- 8464452 TI - The incidence of post-transfusion hepatitis. PMID- 8464453 TI - False positive tests for HIV in a woman with lupus and renal failure. PMID- 8464454 TI - Pneumococcal appendicitis in a man with HIV infection. PMID- 8464455 TI - Extrusion influence on the nutritive value of casein preparations. AB - Effect of extrusion (120 C; 8-12 s; extruder S 45-12-10 U) on amino acids and nutritive value of casein preparations in the form of calcium and low-calcium paracaseinates and in acidic form was studied. The following indices were found to decrease slightly: chemical score (CS) from the range 57.4-58.8 to 57.2-58.1; essential amino acids (EAA) from 86.1-88.3 to 84.9-88.1; NPU from 61.4-67.6 to 60.2-66.6; PER from 2.40-2.47 to 2.38-2.45; apparent digestibility (AD) from 84.9 87.2 to 84.8-87.2; true digestibility (TD) from 90.7-95.3 to 90.4-92.8 and biological value (BV) from 66.6-71.0 to 65.8-69.6. These results prove that the extrusion at 120 C does not result in a significant lowering of the protein quality in the casein preparations. PMID- 8464456 TI - Effect of sex hormones on copper, zinc, iron nutritional status and hepatic lipid peroxidation in rats. AB - Sex dependence of copper, zinc, iron nutritional status and hepatic lipid peroxidation was studied in gonadectomized, hormone substituted and sham-operated male and female rats. The experiment was performed on H-Wistar rats (106 +/- 10 g) fed conventional laboratory food ad libitum for 12 weeks. The estrogen dependence of copper status is fully confirmed by the results of this study. In hormonally active females the malondialdehyde production was depressed which is supposed to be connected with high copper and low triglyceride levels in the liver. The anaemia observed in estrogen substituted rats may be a result of lower lipid peroxidation rate. The levels of retinol and alkaline phosphatase activity in sera are probably influenced by estrogen action. It is suggested that testosterone leads to acceleration of lipid peroxidation. PMID- 8464457 TI - Microsomal alkaline phosphatase activity in retinol deficiency induced albino rats. AB - The investigations showed a significant decrease in the alkaline phosphatase activity of retinol deficient liver (48.6%), kidney (65.8%) and spleen (61.9%), as compared to the controls (100%). An increase in Vmax and Km by 12 to 51.5% and 90.4 to 189%, respectively, was observed in all the tissues in the retinol deficient group, as compared to the controls. Subsequent freezing and thawing reduced the activity of alkaline phosphatase by 22.5 to 35.8% in the experimental group; whereas the reduction in the control group ranged from 8.8 to 21.5%. In the presence of lectins and detergents the activity of alkaline phosphatase decreased in both the groups to different levels. PMID- 8464459 TI - NIH plans to begin AIDS drug trials at earlier stage. PMID- 8464458 TI - Alarm, but little action, on population. PMID- 8464460 TI - NSF does well, NIH does not in Clinton's 1994 budget. PMID- 8464461 TI - OTA panel opens inquiry into patenting of genes. PMID- 8464462 TI - SI units explained. PMID- 8464463 TI - Rall's farewell to frontiers. PMID- 8464465 TI - Biotechnology. Adventure capital. PMID- 8464464 TI - AIDS. I want a new drug. PMID- 8464466 TI - Genentech. Clone your own legend. PMID- 8464468 TI - The Salk. Oxbridge-on-sea. PMID- 8464467 TI - San Diego. Talk of the town. PMID- 8464469 TI - Huntington's disease. The end of the beginning. PMID- 8464470 TI - Malaria. That vaccine passes a trial. PMID- 8464471 TI - Developmental biology. Dorian gray mice. PMID- 8464472 TI - Sperm costs and lifespan. PMID- 8464473 TI - Aluminium in Alzheimer's? PMID- 8464474 TI - Maker's mark. PMID- 8464475 TI - Agrobacterium conjugation and gene regulation by N-acyl-L-homoserine lactones. AB - Conjugal opines secreted by crown gall tumours induce strains of Agrobacterium tumefaciens that are donors of Ti plasmids to produce a diffusible conjugation factor. This enhances the conjugal transfer efficiency of the Ti plasmid in other strains of A. tumefaciens. This factor behaves as a secondary messenger, transmitting the environmental information to tra genes. Here we report the use of spectrometry to show that this factor is identical to synthetic N-(beta-oxo octan-1-oyl)-L-homoserine lactone and confirm that the synthetic compound is biologically active. N-(Hexan-1-oyl)-L-homoserine lactone has also been detected. A closely related molecule, N-(beta-oxo-hexan-1-oyl)-L-homoserine lactone, autoinduces bioluminescence in the distantly related bacterium, Vibrio fischeri. N-Acyl-homoserine lactones thus seem to be conserved molecules in which the length and nature of the lipophilic acyl chain determines the biological function to be regulated. Mutants that do not produce the factor fail to conjugate unless supplied with it in the induction medium (our unpublished data). These data indicate that the conjugation factor is an autoinducer and a key signal molecule in the conjugation system of A. tumefaciens. It is, to our knowledge, the first example of a second messenger molecule in a bacterial conjugation system. PMID- 8464476 TI - Conjugation factor of Agrobacterium tumefaciens regulates Ti plasmid transfer by autoinduction. AB - Conjugal transfer of Ti plasmids from Agrobacterium donors to bacterial recipients is controlled by two types of diffusible signal molecules. Induction is mediated by novel compounds, called opines, that are secreted by crown gall tumours. These neoplasias result from infection of susceptible plants by virulent agrobacteria. The second diffusible signal, called conjugation factor, is synthesized by the donor bacteria themselves. Production of this factor is induced by the opine. Here we show that conjugation is regulated directly by a transcriptional activator, TraR, which requires conjugation factor as a coinducer to activate tra gene expression. TraR is a homologue of LuxR, the lux gene activator from Vibrio fischeri which also requires an endogenously synthesized diffusible coinducer. The two regulatory systems are related; the two activator proteins show amino-acid sequence similarities and the lux system cofactor, autoinducer, will substitute for conjugation factor in the TraR-dependent activation of Ti plasmid tra genes. PMID- 8464477 TI - Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. AB - The transplantation of well defined populations of precursor cells offers a means of repairing damaged tissue and of delivering therapeutic compounds to sites of injury or degeneration. For example, a functional immune system can be reconstituted by transplantation of purified haematopoietic stem cells, and transplanted skeletal myoblasts and keratinocytes can participate in the formation of normal tissue in host animals. Cell transplantation in the central nervous system (CNS) has been proposed as a means of correcting neuronal dysfunction in diseases associated with neuronal loss; it might also rectify glial cell dysfunction, with transplanted oligodendrocyte precursor cells eventually allowing repair of demyelinating damage in the CNS. Here we use co operating growth factors to expand purified populations of oligodendrocyte type-2 astrocyte (O-2A) progenitor cells for several weeks in vitro. When injected into demyelinating lesions in spinal cords of adult rats, created in such a way as to preclude host-mediated remyelination, these expanded populations are capable of producing extensive remyelination. In addition, transplantation of O-2A progenitor cells genetically modified to express the bacterial beta-galactosidase gene gives rise to beta-galactosidase-positive oligodendrocytes which remyelinate demyelinated axons within the lesion. These results offer a viable strategy for the manipulation of neural precursor cells which is compatible with attempts to repair damaged CNS tissue by precursor transplantation. PMID- 8464478 TI - Oncogene ect2 is related to regulators of small GTP-binding proteins. AB - We have developed an efficient expression cloning system that allows rapid isolation of complementary DNAs able to induce the transformed phenotype. We searched for molecules expressed in epithelial cells and possessing transforming potential to fibroblasts, and cloned a cDNA for the normal receptor of a growth factor secreted by NIH/3T3 cells. Here we report a second novel transforming gene, ect2. The isolated cDNA is activated by amino-terminal truncation of the normal product. The Ect2 protein has sequence similarity within a central core of 255 amino acids with the products of the breakpoint cluster gene, bcr (ref. 5), the yeast cell cycle gene, CDC24 (ref. 6), and the dbl oncogene. Each of these genes encodes regulatory molecules or effectors for Rho-like small GTP-binding proteins. The baculovirus-expressed Ect2 protein could bind highly specifically to Rho and Rac proteins, whereas the dbl product showed broader binding specificity to Rho family proteins. Thus ect2 is a new member of an expanding family, whose products have transforming properties and interact with Rho-like proteins of the Ras superfamily. PMID- 8464479 TI - Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. AB - The transcription factor GATA-1 is a fundamental regulator of genes in haematopoietic cell lineages and belongs to a family of factors that bind to the consensus sequence WGATAR. The GATA motif was originally identified in cis regulatory regions of globin and other erythroid-specific genes, but the range of genes controlled by the GATA factors has since expanded. Members of the GATA transcription factor family share a conserved zinc-finger DNA-binding domain, but the expression profile of each GATA factor is distinct. Here we show that a testis form of murine (m)GATA-1 messenger RNA is transcribed from a promoter located 5' to the erythroid first exon, and the remaining exons (which encode the mGATA-1 protein) are used in common by both testis and erythroid transcripts. We use an anti-mGATA-1 monoclonal antibody to show that the factor expressed in erythroid cells is the same as that found in the seminiferous tubules of murine testis. The GATA-1-expressing cells in 10-week-old testis were found only in contact with the basement membrane of seminiferous tubules, suggesting that GATA 1 regulates genes during the earliest stages of spermatogenesis. PMID- 8464481 TI - Criteria for science in the courts. PMID- 8464480 TI - TFIIIC relieves repression of U6 snRNA transcription by chromatin. AB - The U6 small nuclear (sn)RNA gene (SNR6) from the yeast Saccharomyces cerevisiae is transcribed by RNA polymerase III in vivo. This gene is unusual in having a TATA box at position -30, and an essential B-block element located downstream of the T-rich termination signal. The B block is one of the two intragenic promoter elements of transfer RNA genes that are recognized by transcription factor (TF)IIIC (ref. 4). But accurate in vitro transcription of yeast U6 snRNA gene by PolIII in a purified system requires only TFIIIB components, including the TATA box binding protein TBP. Here we report that, after nucleosome reconstitution or chromatin assembly, U6 snRNA synthesis becomes dependent on TFIIIC and on the integrity of the B-block element. This observation resolves an apparent paradox between in vitro and in vivo results concerning the necessity of the downstream B block element and sheds light on a new role of TFIIIC in gene activation. PMID- 8464483 TI - Genome project 'to be done by 1994'. PMID- 8464482 TI - AIDS administrators plan crisis meeting over future of AZT. PMID- 8464484 TI - Patent problems. PMID- 8464485 TI - The shadow of genetic injustice. AB - The effects of the inevitable discoveries emerging from the Human Genome Project will be catastrophic for some. Now is the time for preventative action to be taken. PMID- 8464486 TI - Pharmacology. ET touches down in Houston. PMID- 8464487 TI - Albert B. Sabin (1906-1993) PMID- 8464488 TI - Parasitology. The evolution of virulence. PMID- 8464489 TI - Palaeoanthropology. Secrets of the pit of the bones. PMID- 8464490 TI - Properties of an HIV 'vaccine'. PMID- 8464491 TI - Properties of an HIV 'vaccine'. PMID- 8464492 TI - Largest subunit of Drosophila transcription factor IID directs assembly of a complex containing TBP and a coactivator. AB - The TFIID complex consists of the TATA-binding protein (TBP) and associated factors (TAFs) serving to mediate transcriptional activation by promoter-specific regulators. Here we report the cloning of Drosophila TAFII250 and the assembly of a partial complex containing recombinant TBP, TAFII110 and the C-terminal domain of TAFII250. This triple complex supports Sp1 activation and reveals specific interactions between TAFII250, TBP and TAFII110. PMID- 8464493 TI - Three new human skulls from the Sima de los Huesos Middle Pleistocene site in Sierra de Atapuerca, Spain. AB - Three important fossil hominids were found in July 1992 in the Middle Pleistocene cave site called Sima de los Huesos (Sierra de Atapuerca, Burgos, Northern Spain). One is a complete calvaria (cranium 4), the second a virtually complete cranium (cranium 5), the third represents a more fragmentary cranium of an immature individual (cranium 6). There is a large difference in size between the two adult specimens (for example endocranial volume 1,125 cm3 versus 1,390 cm3). The Atapuerca human remains are dated to > 300,000 years. The Atapuerca cranial sample fits within the 'archaic Homo sapiens' group, but is well differentiated from the Asian Homo erectus group. The extensive Atapuerca human collection is the most complete sample of Middle Pleistocene humans yet discovered from one site, and appears to document an early stage in Neanderthal evolution. PMID- 8464494 TI - Neurotoxicity of a prion protein fragment. AB - The cellular prion protein (PrPC) is a sialoglycoprotein of M(r) 33-35K that is expressed predominantly in neurons. In transmissible and genetic neurodegenerative disorders such as scrapie of sheep, spongiform encephalopathy of cattle and Creutzfeldt-Jakob or Gerstmann-Straussler-Scheinker diseases of humans, PrPC is converted into an altered form (termed PrPSc) which is distinguishable from its normal homologue by its relative resistance to protease digestion. PrPSc accumulates in the central nervous system of affected individuals, and its protease-resistant core aggregates extracellularly into amyloid fibrils. The process is accompanied by nerve cell loss, whose pathogenesis and molecular basis are not understood. We report here that neuronal death results from chronic exposure of primary rat hippocampal cultures to micromolar concentrations of a peptide corresponding to residues 106-126 of the amino-acid sequence deduced from human PrP complementary DNA. DNA fragmentation of degenerating neurons indicates that cell death occurred by apoptosis. The PrP peptide 106-126 has a high intrinsic ability to polymerize into amyloid-like fibrils in vitro. These findings indicate that cerebral accumulation of PrPSc and its degradation products may play a role in the nerve cell degeneration that occurs in prion-related encephalopathies. PMID- 8464495 TI - Correlation of expression of Wnt-1 in developing limbs with abnormalities in growth and skeletal patterning. AB - The Wnt genes are members of a family of vertebrate genes related to the Drosophila gene wingless (wg). They encode secreted molecules that are thought to be important in patterning and growth control during ontogenesis. Several such genes are transcribed in localized domains during limb budding and morphogenesis. We report here a congenital limb malformation in a mouse transgenic line that ectopically expresses Wnt-1 in the developing limbs. The hemizygote phenotype, which is inherited as an autosomal dominant trait, presents extensive distal truncations of skeletal elements, skeletal fusions and interdigital webbing. The data shown here demonstrate that abnormal Wnt-1 expression is correlated with retarded mesenchymal condensations replaced by highly proliferative cells in the limb bud. This seems to lead to an inability of the affected cells to participate in normal skeletal development leading to the adult defects. PMID- 8464496 TI - Interaction between a transcriptional activator and transcription factor IIB in vivo. AB - Transcription of messenger RNA-encoding genes in vitro requires many protein factors. Transcription factor IID, possibly with the cooperation of TFIIA, binds to the TATA element of the promoter, forming a complex that can bind TFIIB (refs 6, 7) followed by RNA polymerase II (refs 6, 8) and other factors. One or more of these steps is thought to be facilitated by gene-specific transcriptional activation proteins; this seems to require TFIID-associated auxiliary factors and may involve direct contact between the activator and TFIID and/or TFIIB. If such contact is necessary in vivo, activation might conceivably be blocked by a TFIIB derivative containing the sequences necessary for this interaction, but lacking those necessary for binding to the rest of the transcriptional apparatus, an effect similar to that referred to as squelching or transcriptional interference. Here we show that the activity of the glutamine-rich fushi tarazu activation domain is indeed blocked by truncated TFIIB derivatives in Drosophila Schneider L2 cells, suggesting that it is mediated by interactions with TFIIB. PMID- 8464497 TI - Human lysozyme gene mutations cause hereditary systemic amyloidosis. AB - Hereditary non-neuropathic systemic amyloidosis (Ostertag-type) is a rare autosomal dominant disease in which amyloid deposition in the viscera is usually fatal by the fifth decade. In some families it is caused by mutations in the apolipoprotein AI gene but in two unrelated English families under our care the amyloid deposits did not contain apoAI, despite a report that this may have been the case in one of them. Lysozyme is a ubiquitous bacteriolytic enzyme present in external secretions and in polymorphs and macrophages, but its physiological role is not always clear. Here we report that in these two families, lysozyme is the amyloid fibril protein. Affected individuals are heterozygous for point mutations in the lysozyme gene that cause substitution of highly conserved residues, namely threonine for isoleucine at position 56 in one family, and histidine for aspartic acid at residue 67 in the other. Amyloid fibrils from one individual were composed of the full-length Thr-56 variant lysozyme molecule. To our knowledge, this is the first report of naturally occurring variants of human lysozyme and of lysozyme-associated disease. As the structures of human and hen egg-white lysozyme are known to atomic resolution and their folding and structure-function relationships have been exhaustively analysed, our observations should provide a powerful model for understanding amyloidogenesis. PMID- 8464498 TI - Interactions of three domains distinguishing the Ras-related GTP-binding proteins Ypt1 and Sec4. AB - The genes SEC4 and YPT1 encode Ras-related GTP-binding proteins in the yeast Saccharomyces cerevisiae. Ypt1 is necessary for vesicular transport from the endoplasmic reticulum to the Golgi, whereas Sec4 is required for fusion of post Golgi secretory vesicles to the plasma membrane. Recently, three structural domains have been proposed to specify the stage in cellular transport at which members of the Sec4/Ypt1/Rab family act: the effector domain, the C-terminal hypervariable region, and a region corresponding to loop 7 in the structure of p21ras (ref. 8). Here we use Sec4/Ypt1 chimaeras to show that these three regions cooperate to specify Ypt1 function and that the C-terminal hypervariable region is needed for Ypt1 localization to the Golgi. Unexpectedly, we found that a single chimaera can function as either Ypt1 or Sec4 without missorting carboxypeptidase Y or invertase. PMID- 8464500 TI - The Caenorhabditis elegans genome sequencing project: first steps in automation. AB - Novel biochemical processes using magnetic particles have been automated to provide a robotic system to perform processes for large-scale shotgun sequencing. PMID- 8464499 TI - Specificity domains distinguish the Ras-related GTPases Ypt1 and Sec4. AB - The essential Ras-related GTPases Ypt1 and Sec4 act at distinct stages of the secretion pathway in the yeast Saccharomyces cerevisiae: Ypt1 is required for vesicular transport from the endoplasmic reticulum to the Golgi apparatus, whereas Sec4 is required for fusion of secretory vesicles to the plasma membrane. Here we use chimaeras of the two proteins to identify a 9-residue segment of Ypt1 that, when substituted for the analogous segment of Sec4, allows the chimaera to perform the minimal functions of both proteins in vivo. This segment corresponds to loop L7 of the p21ras crystal structure. Substitution of a 24-residue Ypt1 segment, including the residues just mentioned, together with 12 residues of Ypt1 corresponding to the 'effector region' of p21ras (loop L2; refs 7,8), transforms Sec4 into a fully functional Ypt1 protein without residual Sec4 function. PMID- 8464501 TI - Venter's venture. PMID- 8464502 TI - Vaccine compromise. PMID- 8464503 TI - Synergen trims sails to survive. PMID- 8464504 TI - Spain expands despite financial and logistical hurdles. PMID- 8464505 TI - Japan increases share of Human Frontier awards. PMID- 8464506 TI - Russian nuclear accident opens up military complex. PMID- 8464507 TI - NIH genome centre begins build-up. PMID- 8464508 TI - US test of AIDS vaccines is broadened beyond VaxSyn. PMID- 8464509 TI - Interferon-tau. PMID- 8464510 TI - Neurobiology. Organizing the cerebrum. PMID- 8464511 TI - Should a lion change its spots? PMID- 8464512 TI - A structural motif in the variant surface glycoproteins of Trypanosoma brucei. AB - The variable domain of the trypanosome variant surface glycoprotein (VSG) ILTat 1.24 has been shown by X-ray crystallography to resemble closely the structures of VSG MITat 1.2, despite their low sequence similarity. Specific structural features of these VSGs, including substitution of carbohydrate for an alpha helix, can be found in other VSG sequences. Thus antigenic variation in trypanosomes is accomplished by sequence variation, not gross structural alteration; the extensive sequence differences among VSGs may be required for another reason, such as the avoidance of recognition by helper T cells. Additionally, VSG sequences are found to define families, within a VSG superfamily, which have evolved in the trypanosome genome. PMID- 8464513 TI - Clonal dispersion in proliferative layers of developing cerebral cortex. AB - In the adult cerebral cortex, many retrovirally labelled clones are widely dispersed, though the mechanisms of this dispersion are not well understood. Here we investigate the temporal sequence of clonal dispersion after labelling progenitors of rat cortical cells with replication-incompetent retroviruses at early stages of cortical neurogenesis, 14-15 days after conception (E14/15). The location of labelled daughter cells was determined 3, 6 or 10 days later. Labelled sibling cells were radially arrayed three days after infection (E18). In contrast, by six days after infection (E20/21), 43% of cortical clones were dispersed non-radially by at least 500 microns. Four of these widespread clones were dispersed longitudinally by > or = 2 mm, implying sustained rates of dispersion of > 15 microns per hour. Dispersed sibling cells occurred within proliferative zones of the forebrain in 35% of widely dispersed clones, suggesting that some dispersion reflects movement of dividing cells. Some clones dispersed beyond the neocortex into the olfactory bulb. Progenitor cell dispersion represents a previously unrecognized mode of migration by which sibling cells become widely dispersed in the developing forebrain. PMID- 8464514 TI - Dispersion of neural progenitors within the germinal zones of the forebrain. AB - One of the early events in the establishment of regional diversity in brain is the subdivision of the forebrain into the cerebral cortex and underlying basal ganglia. This subdivision is of special interest, owing to the striking difference in cellular patterning in these two regions. Whereas the dorsal aspect of the telencephalon gives rise to the laminar, cortical regions of brain, the basal aspect gives rise to nuclear, subcortical regions. To examine early events in the regionalization of the forebrain, we visualized cell movement within the ventricular zones of the dorsal and basal regions of the E15 murine telencephalon. Over an 8-24-hour observation period, labelled cells moved extensively in the plane of the cortical ventricular zone. Cell dispersion was restricted, however, at the border between the cortical ventricular zone and the lateral ganglionic eminence, the basal telencephalic ventricular zone. We suggest that this restriction of cell movements establishes a regional pattern of neurogenesis in the developing brain. PMID- 8464515 TI - Radial mosaicism and tangential cell dispersion both contribute to mouse neocortical development. AB - The mammalian neocortex is generated by waves of migrating cells originating from the ventricular zone. Radial migration along radial glia has been proposed as the dominant mechanism for this process. The radial unit hypothesis is poorly supported by retroviral lineage studies, however, and although some clones show limited radial organization, the emphasis appears to be on widespread tangential dispersion. Here we investigate the pattern of cortical cell dispersion using transgenic mice in which roughly half of the brain cells are coloured by a transgene. We find that the neocortex is randomly divided into diffused bands, the majority of cells within each band have the same colour, and their radial orientation suggests radial dispersion. Superimposed upon this was a significant contribution by tangentially dispersed cells that did not respect clonal borders. These observations indicate that cortical specification is not dependent upon a single mechanism of cell allocation, but that both radial mosaicism and tangential cell migration are involved. PMID- 8464516 TI - Tyrosine kinase activation through the extracellular domains of cytokine receptors. AB - Interaction of cytokines with their membrane receptors induces the proliferation and differentiation of a specific lineage of haematopoietic progenitors. The molecular mechanism of cytokine receptor-mediated signal transduction is unclear because these receptors do not have tyrosine kinase activity. Interleukin-3 and erythropoietin, however, induce transient tyrosine phosphorylation of a common set of proteins as a growth signal, and interleukin-2 induces phosphorylation of an overlapping but distinct set of proteins. Here we show that chimaeric receptors consisting of the extracellular domains of the erythropoietin receptor and the cytoplasmic domains of the interleukin-2 (or interleukin-3) receptor induce an erythropoietin-dependent tyrosine phosphorylation in interleukin-3 dependent Ba/F3 cells; however, chimaeric receptors composed of the extracellular domains of the interleukin-2 receptor and the cytoplasmic domains of the erythropoietin (or interleukin-3) receptor apparently transmit an interleukin-2 dependent signal. Our results indicate that these cytokines transmit distinct signals for activation of specific tyrosine kinases through the extracellular rather than cytoplasmic domains of the receptors. PMID- 8464517 TI - Budding from Golgi membranes requires the coatomer complex of non-clathrin coat proteins. AB - Do the coats on vesicles budded from the Golgi apparatus actually cause the budding, or do they simply coat buds (Fig. 1)? One view (the membrane-mediated budding hypothesis) is that budding is an intrinsic property of Golgi membranes not requiring extrinsic coat proteins. Assembly of coats from dispersed subunits is super-imposed upon the intrinsic budding process and is proposed to convert the tips of tubules into vesicles. The alternative view (the coat-mediated budding hypothesis) is that coat formation provides the essential driving force for budding. The membrane-mediated budding hypothesis was inspired by the microtubule-dependent extension of apparently uncoated, 90-nm-diameter membrane tubules from the Golgi apparatus and other organelles in vivo after treatment with brefeldin A, a drug that inhibits the assembly of coat proteins onto Golgi membranes. This hypothesis predicts that tubules will be extended when coat proteins are unavailable to convert tubule-derived membrane into vesicles. Here we use a cell-free system in which coated vesicles are formed from Golgi cisternae to show that, on the contrary, when budding diminishes as a result of immunodepletion of coat protein pools, tubules are not formed at the expense of vesicles. We conclude that coat proteins are required for budding from Golgi membranes. PMID- 8464518 TI - Defective mismatch binding and a mutator phenotype in cells tolerant to DNA damage. AB - Acquired resistance to alkylating agents such as N-methyl-N-nitrosourea or N methyl-N'-nitro-N-nitrosoguanidine results from the ability to tolerate the potentially cytotoxic methylated base O6-methylguanine (m6-G) in DNA. In the absence of repair by demethylation in situ, m6-G is probably lethal through its inappropriate processing by the cell. DNA mismatch correction is an attractive candidate for the processing function because although it is replicated, m6-G has no perfect complementary base. Thus, m6-G in DNA might provoke abortive mismatch repair and tolerance could subsequently arise through loss of a mismatch repair pathway. Mismatch correction helps maintain genomic fidelity by removing misincorporated bases and deaminated 5-methylcytosine from DNA, and its loss by mutation confers a mutator phenotype on Escherichia coli. Here we describe human and hamster cell lines that are tolerant to N-methyl-N-nitrosourea and are defective in a DNA mismatch binding activity. The loss of this activity, which acts on G.T mispairs, confers a mutator phenotype. PMID- 8464519 TI - [Selection--a key concept for the structural and functional self-organization of the brain?]. AB - Starting from well-known concepts and theoretical work in biology and economics, the self-organization of the brain is defined as a three-fold selection process with three different time scales. As a morphogenetic and functional principle, selection operates at a phylogenetic, an ontogenetic, and a cognitive level. Especially the hypothesis of a fast cortical selection extends the explanatory power of this central biological concept to conscious higher brain functions. PMID- 8464520 TI - Time delay of maximal human thyroid 131I uptake after the Chernobyl accident. PMID- 8464521 TI - Cardiomyocytes of adult mice in long-term culture. PMID- 8464522 TI - [Lumbar spinal stenosis]. PMID- 8464523 TI - [The professional secret following the patient's death]. PMID- 8464524 TI - [Diagnosis and treatment of soft tissue sarcomas]. PMID- 8464525 TI - [Breast cancer in pregnancy]. PMID- 8464526 TI - [Reconstructive surgery of the head and neck region using free muscle flaps]. AB - Twenty-seven patients who underwent microvasculosurgical free tissue transfers for head and neck reconstruction with a M. rectus abdominis or M. latissimus dorsi flap are reviewed. In this series the flap reconstruction was completed in 15 patients with extraoral defects, in six patients with an intraoral defect and in six patients with a combined intra and extraoral defect. Split thickness skin graft coverage was used in all cases. All free muscle grafts survived and good take of the split skin was obtained. In extraoral defects coverage of free muscle transfer with split thickness skin grafts results in a better color match than with musculocutaneous flaps and complements the appearance and pliability of the free muscle flap. Reshaping and three-dimensional positioning made reconstruction of every intraoral defect and combined intra and extraoral defects possible. In skilled hands, free tissue transfer provides a reliable method for reconstruction of almost every defect in the head and neck. PMID- 8464527 TI - [Combination heart-lung transplantation in children: 4-year experience in London]. AB - Since 1987, 21 children under 16 years of age have undergone combined heart and lung transplantation at Great Ormond Street Hospital, London. All children had terminal pulmonary or cardiopulmonary disease. Eight children died one day to 21 months after operation. Actuarial survival was 76% (SEM 10) at 1 year and 60% (SEM 12) at 3 and 4 years after transplantation. 13 children were alive, and all took part in all age-appropriate activities. PMID- 8464528 TI - [Wishes of residents in internal medicine with relation to working week, part time work, career length and practice pattern]. AB - To investigate the wishes and ideas about length of working week, part-time work, length of career and future kind of establishment, a questionnaire was sent to all Dutch registrars of internal medicine. In the opinion of more than 70 percent of the registrars, the length of a full-time working week of an internist should be less than 50 hours. Of all registrars (62% men and 38% women), 68% would decide in favour of part-time work if the length of a full-time working week of an internist were to remain at about 68 hours (common length of a working week of Dutch internists nowadays). 33% would still like to work part-time when the length of a full-time working week became as they desired (about 47 hours). The preferred length of their career was for most registrars less than 30 years. The majority preferred a tenure to a position in a partnership. In conclusion, the wishes about the future of the registrars of internal medicine differ markedly from the current situation. PMID- 8464529 TI - [Perinatal asphyxia and postpartum resuscitation: starting always, but when to stop?]. PMID- 8464530 TI - [Menstruation pattern and month of birth]. PMID- 8464531 TI - [Menstruation pattern and month of birth]. PMID- 8464532 TI - [Lupus erythematosus; current treatment methods]. PMID- 8464533 TI - Special issue dedicated to Dr. Paul Greengard. PMID- 8464534 TI - Brain dopamine receptors: 20 years of progress. AB - I present a brief overview of the contributions of Paul Greengard's laboratory to the field of dopamine receptor research. I show that the work on the biochemical pharmacology of dopamine receptors was part of the intellectual foundation for the division of dopamine receptors into two general pharmacological categories. PMID- 8464535 TI - Neuronal localization of the tyrosine-specific protein kinase p62c-yes in rat basal ganglia. AB - The cellular localization of the tyrosine-specific protein kinase p62c-yes, the product of the proto-oncogene c-yes, has been examined in the striatonigral neurons which interconnect the rat neostriatum and substantia nigra. Although p62c-yes was more enriched in the neostriatum than in the substantia nigra, excitotoxin-induced necrosis of nerve cells in the neostriatum led to 50-60% decreases of p62c-yes both in the lesioned neostriatum and in the ipsilateral substantia nigra. Hence, the p62c-yes tyrosine kinase is present both in the cell body region and in the axonal and nerve terminal region of the striatonigral neurons. This localization indicates that the enzyme may be involved in both presynaptic and postsynaptic functions in mammalian forebrain neurons. PMID- 8464536 TI - Biogenesis of small synaptic vesicles and synaptic-like microvesicles. PMID- 8464538 TI - Neuropeptides: Function and Pharmacology. 3rd meeting of the European Neuropeptide Club. Cambridge, United Kingdom, 5-7 April 1993. Abstracts. PMID- 8464539 TI - The restoration of the function of the hypophyseal-gonadal system following its prolonged suppression by luliberin agonists. PMID- 8464537 TI - Kinetic properties of bovine brain protein L-isoaspartyl methyltransferase determined using a synthetic isoaspartyl peptide substrate. AB - Protein L-isoaspartyl methyltransferase, an enzyme enriched in brain, is implicated in the repair of age-damaged proteins containing atypical, isoaspartyl peptide bonds. We have investigated the kinetics of methylation using a synthetic peptide substrate having the structure Trp-Ala-Gly-Gly-isoAsp-Ala-Ser-Gly-Glu. Double-reciprocal plots of initial velocity versus concentration of S adenosylmethionine (AdoMet) at different fixed concentrations of peptide gave straight lines converging at a positive 1/v value and a negative 1/AdoMet value. The product S-adenosylhomocysteine (AdoHcy) was a competitive inhibitor towards AdoMet and a linear mixed-type inhibitor towards peptide. These results are consistent with the rapid-equilibrium random sequential bi-bi mechanism previously proposed for the enzyme, but they also reveal the formation of the dead-end, enzyme-peptide-AdoHcy, complex. The rate constants were: Vmax = 32-34 nmol/min/mg, Kpeptide = 7.6-9.4 microM, KAdoMet = 1.9-2.2 microM, alpha = 0.43 0.53, KAdoHcy = 0.08 microM, gamma = 2.9. The interaction factors alpha and gamma indicate that binding of enzyme to peptide increases its affinity for AdoMet and decreases its affinity for AdoHcy. Methylation was linear with time throughout the transfer of 2 mol of methyl groups/mol of enzyme. This absence of burst kinetics suggests that slow release of products cannot explain the low turnover number. PMID- 8464540 TI - An investigation of the topographic organization of cortical electrical activity during hypnotic analgesia. PMID- 8464541 TI - Neuronal analysis of hunting behavior of the pteropod mollusc Clione limacina. AB - The neurons of the cerebral ganglia controlling the movements of the hunting apparatus of the predatory pelagic pteropod mollusc, Clione limacina, are described in detail. A large group of high-threshold, electrically interconnected neurons, A, was identified, the impulse activity of which leads to the opening of the skin folds and the forward ejection of the hunting tentacles of the clione. Group B neurons which exhibit a constant background activity and which receive powerful inhibitory inputs from the A cells, conversely, induce the contraction and the withdrawal of the hunting tentacles into the head. The third group, are the C neurons, the impulse activity of which leads to the drawing together of the skin folds covering the hunting apparatus. The effect of such mediators as serotonin, dopamine, and gamma aminobutyric acid acid on the identified neurons was investigated. Serotonin depolarizes both A and B neurons, but the activation of the hunting apparatus appears to be an integrated effect: the activated A neurons inhibit the B neurons due to powerful IPSP, interrupting the direct excitatory effect of serotonin. Dopamine in various concentrations exerts the opposite effect: at low concentrations only B cells are activated and the tentacles are withdrawn into the head; at high concentrations the A neurons begin to operate; these neurons inhibit the B cells and activate the hunting apparatus. GABA exerts an integral, well-coordinated effect on the neurons controlling the movements of the hunting apparatus, and effect which is directed toward the activation of hunting behavior: it depolarizes-activates A neurons and hyperpolarizes-inhibits B and C neurons. PMID- 8464542 TI - The role of the specific and nonspecific afferent systems in the mechanism of changes in evoked cortical responses in the presence of vibration. AB - The interrelationship of the activity of specific and nonspecific afferent systems in the mechanism of changes in the electrical activity of the cortex under the influence of vibration was studied under chronic experimental conditions. The character of the postvibrational shifts in the vestibulo- and reticulocortical evoked responses in the presence of the isolated and combined disengagement of the specific (vestibular) and nonspecific afferent systems of the brain was investigated. It was established that vestibular afferentation plays a significant role in the mechanism of postvibrational shifts in the vestibulocortical evoked responses, whereas nonspecific, as well as proprioceptive, somatic, and visceral as well as other inputs play the dominant role for the reticulocortical system of integration. PMID- 8464543 TI - The chemical nature of the hypothalamocortical activation underlying drinking behavior. AB - The injection of cholinergic substances (carbocholine, carbathin [karbatin], acetylcholine) into the lateral field of the hypothalamus of cats is accompanied by the appearance in the electrohypothalamogram of characteristic hypersynchronized activity and drinking behavior. The swallowing of water temporarily stops the hypersynchronized activity; the injection of adrenaline into the hypothalamus elicits the same effect. The injection of the same cholinergic preparations into the posterior sigmoid gyrus of the cerebral cortex is accompanied by similar, but less pronounced bioelectrical and behavioral effects. The presentation of a closed drink dispenser containing water to the animals against the background of cholinergic activation of the hypothalamus or cortex leads to desynchronization of the bioelectrical activity and suppression of the bursts of hypersynchronized activity. The drinking behavior of cats which appears on the basis of centrally created thirst motivation reflects the activity of a primary dominant focus in the hypothalamus and of a secondary dominant focus in the sensorimotor cortex. These foci are cholinergic in nature. The cessation of the drinking behavior may be related to the activation of adrenergic mechanisms of the same brain structures. PMID- 8464544 TI - The features of the influence of "reward areas" on the electrical activity of the parafascicular complex of nuclei in the developing rabbit. AB - The influence of the electrostimulation of "reward areas", preliminarily identified by the self-stimulation technique, on the evoked potentials recorded in the parafascicular complex of the thalamus in response to peripheral nociceptive stimulation was studied in 35 rabbits, of 41-60 days of life. When comparison was made of the data obtained with the results of studies carried out previously in adult animals and in rabbits from the 30th-40th days, in addition to common characteristics, features of these influences which were characteristics only for the age interval under investigation were distinguished. The antinociceptive influences of the "reward areas" on the evoked potentials in the parafascicular complex were less pronounced with respect to a number of parameters in the period of the rabbits life occupying the intermediate position between the over-excitable and adult periods of development. PMID- 8464545 TI - Specific features of the electroretinogram of vertebrates induced by X-rays. AB - The net electroretinograms of dark-adapted retinas of the common frog in situ were investigated on an automated experimental system with programmed control and electronic differentiation of biopotentials with respect to the first and second derivatives. It was demonstrated that X-rays elicit an electroretinogram consisting of two components, provisionally called the first and second X-ray reactions (X-1 and X-2), which differ with respect to their parameters from electroretinograms elicited under the same conditions by red and blue light. The administration of sodium azide, sodium nitrate, monoiodo-acetate and other substances alter the X-1 and X-2 as well as the photo-induced ERGs in different ways; this indicates their relative independence and different mechanisms of the occurrence and passing of excitation across the structures of the retina, and makes it possible to partially isolate these for individual study. Thus, the assertion of a number of investigators regarding the absence of specific features in the X-ray induced electroretinograms becomes problematical. The discovery of X ray-specific reactions in the retina makes it possible to hope that the radiological phosphene (the X-ray phosphene) may serve as a test for the determination of the individual radiational excitability of the central nervous system. PMID- 8464546 TI - The influence of picrotoxin on the methylation of phospholipids of the olfactory cortex of the brain of rats. AB - It was demonstrated that a decrease in the intensity of methylation of phosphatidylethanolamine in sections of rat olfactory cortex is observed 15 min following the introduction of picrotoxin (10(-5) M) into the incubation medium. The decrease in the intensity of methylation of phospholipids may be closely linked to the opening of ion channels, since it is known that maximal depolarization of the membranes is observed during this period of the effect of the preparation. PMID- 8464547 TI - Cyclical processes in neuronal populations of the cat somatosensory cortex during extero- and interoceptive activation and in the course of its extinction. AB - The EEG reactions were recorded in chronic experiments in awake cats and the slow periodic changes in the frequency of the multicellular impulse activity were observed at points (standard localization) of the somatosensory (1) zone of the cortex. Results of the analysis of both processes were combined in graphs in a single time scale. The correlation of the expressivity of the activation reaction and degree of modulation of the cyclical fluctuations of the frequency of the impulse activity were followed both during the action of exteroceptive (conditional, light; unconditional, sound) and the interoceptive (mechanical and chemical) stimuli. A particular characteristic of the interoceptive stimulation as compared with the exteroceptive consisted in the inertia of the respondent reaction and the lesser contrast in relation to the background. During the extinction of the responses the decrease in the activation reaction correlated with a decrease in the initial (after the switching on of the stimulus) fluctuation of the frequency of the multicellular impulse activity. The data obtained serves as proof of the unity of the two processes: the regulation of the activation of the brain and the regulation of the periodicity of the neuronal impulse activity. PMID- 8464549 TI - The epidemiology of congenital abnormalities of the central nervous system in children. PMID- 8464548 TI - The effectiveness of amiridin in senile dementia of the Alzheimer's type. PMID- 8464551 TI - American Academy of Neurology 45th annual meeting New York, New York, April 25 May 1, 1993. Abstracts. PMID- 8464550 TI - Postural motoric and cognitive functions in children with dyspraxia. PMID- 8464552 TI - [Hemodynamic changes in liver and multi-organ transplantation]. AB - Multivisceral transplantation is a surgical technique developed as treatment for abdominal metastatic and/or multifocal malignancies. At present its clinical employment is reduced by our fragmentary knowledge of the intraoperative and postoperative outcome. The aim of this study is to compare intraoperative hemodynamic and respiratory changes during multivisceral transplantation (MTV, n = 12) and liver transplantation (OLTX, n = 14). The observations have been carried out a 4 phases: basal (I), visceral (II), reperfusion (III), final (IV). Phase I does not show differences between MTV and OLTX. In phase II MTV presents a lower temperature (T) and pulmonary arterial pressure (PAP) (p > 0.05). Phase III is marked by increasing T differences (p < 0.05), lower cardiac frequency (CF), pH and base excess (BE) (p < 0.05). PAP and cardiac output (CO) show a higher value in MTV (p < 0.05). Phase IV reports the vital signs close to normality in both groups, except pH in MTV (p > 0.05). PMID- 8464553 TI - [Liver injury in abdominal trauma. Review of the literature and personal observations]. AB - In patients who suffered abdominal trauma, the liver is the most frequently involved organ, except the spleen. The % rises from 1520% to 30% if trauma is closed or open. Liver injury may spread from a simple parenchymal contusion to a break in vessels or biliary ducts. Life risk is related to hemorrhage. The mortality is due to: 1) extension of the injured liver surface, 2) possible damage to big vessels, 3) intra or extra abdominal associated injury in case of multiple trauma. It is important to known the kind of injury to choose the best therapy, not necessary surgical. The authors report on 15 patients with thoracoabdominal trauma and liver damage, comparing their cases with literature observations. PMID- 8464554 TI - [Pneumoperitoneum in preparation for surgery of large ventral hernia]. AB - Reparative surgery of ventral hernia may be relatively simple or, on the other hand, the surgeon may be confronted with a number of tactical and technical problems. Many of these are caused by the "loss of the right of domicile". In order to avoid this particular condition it is useful to resort to preoperative pneumoperitoneum. This method entails the gradual and progressive introduction of air into the peritoneal cavity. In this way abdominal capacity is increased and it is therefore possible to re-insert all the viscera into their natural cavities avoiding all the harmful consequences for respiratory and cardio-circulatory organs following forced replacement. Preoperative pneumo-peritoneum is a relatively well consolidated surgical technique in large scale eventration. The methods is simple to perform and has a low incidence of complications. PMID- 8464556 TI - [Excisional and reconstructive treatment of stage IV tumors in the oral cavity. Results and limits]. AB - The patients with advanced stages of intraoral cancer, having a limited life expectancy, are often considered non-surgical cases. Radiochemotherapy does not warrant an acceptable quality of life. The authors analysed the data obtained from their experiences in resections that had been extensive, as well as, reconstructive treatment of these kinds of neoplasms. They tried to evaluate the demolitive and reconstructive approach, in terms of morbidity, functional results and survival rate. Thirty-six patients, treated from January 1990 to August 1991 for advanced intraoral cancer, were considered in this study; 58% of the cases had primary tumors and 42% had recurrences. The reconstructive procedure used in all cases, was the pectoralis major myocutaneous flap. Even though the expected oncological results had been poor, the functional ones, had been quite encouraging. In fact, the assessment of speech and swallowing was extremely satisfactory, respectively in 82% and 89% of cases. The morbidity related to the flap procedure had been low. The quality of the residual life of the patients was good, especially if compared with the life of those patients who had not been treated. In conclusion, the authors maintain that even patients with limited prognosis may be considered as potential candidates for demolitive and reconstructive treatment. PMID- 8464555 TI - [Osteosarcoma of the extremities metastatic at presentation. Results obtained with primary chemotherapy followed by simultaneous resection of the primary and metastatic lesion]. AB - From September 1986 to September 1990 35 patients affected by osteosarcoma of the extremities with synchronous metastasis were treated with two cycles of high-dose methotrexate IV, cisplatin IA and adriamycin IV followed, in 22, by simultaneous resection of the primary and metastatic tumor. Six patients progressed and were not operated on, 7 patients with complete response of pulmonary nodules underwent surgical resection of the primary lesion. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumour was "good" (90% or more tumour necrosis) in 8 patients (27%) and "poor" (less than 90% of tumour necrosis) in 21 (73%) while in the 75 metastatic nodules the resulting necrosis was good in 18 (24%) and poor in 57 (74%). A good correlation between the histological response in the primary and metastatic tumour was observed. At an average follow-up of 30 months (R 12-60), 13 patients are alive, 10 disease-free, and 3 with uncontrolled disease. This data suggest that prognosis of osteosarcoma of the extremities with synchronous metastases remains poor even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non metastatic osteosarcoma: to introduce new drugs postoperatively in patients poor responder can allows a better treatment of microscopic disease and can improve the prognosis for these patients. PMID- 8464557 TI - [Surgical treatment of neoplasms of the lip]. AB - The authors examine the surgical treatment of lip cancer and describe the reconstructive techniques used for various tumour localisation and extensions. In addition, they illustrate the current opinions regarding the treatment of satellite lymph node areas. PMID- 8464558 TI - [The Senning procedure in Budd-Chiari syndrome associated with complete portal vein thrombosis]. AB - The authors report their experience of one case of Budd-Chiari syndrome with total thrombosis of the portal vein. The patient was undergoing hepatico-atrial anastomosis with Senning's procedure. The original technique utilised extracorporeal circulation with hypothermia; the authors utilised venovenous bypass from femoral vein to axillary vein. Anastomosis function is proved with nuclear magnetic resonance and echo-Doppler on year after operation. Senning's procedure is feasible in the case of Budd-Chiari syndrome with total portal thrombosis with venovenous bypass without extracorporeal circulation with hypothermia. PMID- 8464559 TI - [Primary stones of the common bile duct]. AB - Primary stones can probably form, although rarely, in the common bile duct. The authors report a series of six cases which they considered as primary common duct stone disease and, in order to get more precise information on this problem, they review the literature on the subject. This disease would be caused by the presence of a lithogenic bile which, with a chronic obstruction of the Vater's ampulla, could let lithiasic particles accumulate in the common bile duct. On the basis of this hypothesis and in order to perform a correct procedure that allows easy drainage of the bile to the intestine to the chronic use of litholytic drugs. PMID- 8464560 TI - [Malignant schwannoma of the omentum. Considerations in a clinical case]. AB - Authors describe a rare case of malignant schwannoma of the omentum. The diagnosis of schwannomas is often late because of the absence of early clinical signs. Clinical, diagnostic and histopathological considerations of these neoplasias are described in this work. PMID- 8464561 TI - [Rheologic features of erythrocytes in beta-thalassemia minor]. AB - The study assessed the physical characteristics of erythrocytes, viscosity and deformability, measured by a widely described double-filtration method. At the same plasma-cell viscosity was measured and the importance of the rigidity of RBC was evaluated as one of the many forces which interact among the cells and between the plasma and cells. The results showed a marked increase in corpuscular viscosity with reduced deformability, and a significant diminution of plasma erythrocytic viscosity, whereas total viscosity remained unaltered. These parameters do not correlate with the quantitative pathological alterations of HbA2, but only with RDW-SD. Alterations of the proteic components with a relative increase in the alpha-chains of the erythrocytic membrane are thought to be responsible for these anomalies, by means af the modifications that the excess of alpha-globin causes to the structure and function of erythrocytic membrane; but the quantity of globin is not the decisive factor, and in fact the introduction of the beta-chains are able to correct erythrocytic deformability (Sorensen). Membrane rigidity is probably independent and unrelated to microcytemia, because these erythrocytes, have an excess of surface in relation to their volume, due to the simultaneous alteration of permeability. The diminished plasma-erythrocytic viscosity should be connected with the prevalence of repulsing forces, due to erythrocytic rigidity in relation to the attracting forces due to the proteic fractions which remain unchanged. PMID- 8464562 TI - [Activated partial thromboplastin time. Evaluation of sensitivity and validity for determination of factor VIII coagulant activity]. AB - The authors evaluate the sensibility and validity of some reagents for activated partial thromboplastin time during construction of a curve for measurement of factor VIII coagulant activity. For every reagent three clotting factor VIII deficient plasmas have been used; Baldacci, Dade and Behering. Significant differences in results between every reagent for aPTT and laboratory have been observed. By these results the Authors show the best reagent for aPTT. Future fields of research have been analyzed. PMID- 8464563 TI - [Peptic activity of gastric juice in chronic gastritis. Morpho-functional aspects]. AB - The aim of this study has been to evaluate peptic activity in gastric juice and gastric peptic cell mass in chronic gastritis. As regard peptic activity, there is a close correlation between it and the peptic gastric cell mass considered globally and expressed as Peptic Gastric Index (PGI), resulting from the individual average between fundic peptic index (chief cells + fundic muco-peptic cells) and antral peptic index (antral muco-peptic cells), both obtained by multiplying the number of peptic cells per mm2 by the thickness of respectively fundic and antral gland layer). In particular fundic and antral superficiale gastritis does not involve changes in peptic activity in gastric juice. On the contrary, in case of fundic pre-atrophic or atrophic there is a significant drop of peptic activity in gastric juice, regardless of the histological condition of the antrum. The lowest value of peptic activity may be noticed in case of atrophic pan-gastritis. Pre-atrophic and atrophic gastritis limited to the antrum -with superficial fundic gastritis--does not involve significant decreases of peptic activity in gastric juice. In this experiences Helicobacter pylori seem to influence peptic secretion: in fact, there is an increases of peptic activity in gastric juice in case of chronic pre-atrophic gastritis HP+. PMID- 8464564 TI - [Local immune response in neurofibromatosis type 1 and type 2]. AB - Neurofibromatosis, in all its variant forms, is a hereditary disease characterized by dysplasia, neoplasia, and the tendency to expand and undergo malignant transformation. We underline the presence of chronic inflammation and of immunologic interdependency. The immune reactions against the non-self have been investigated histologically in light of the concepts of immunosurveillance and immunotolerance. Such investigations would ameliorate subsequent studies and favour the employment of immunomodulatory treatments. PMID- 8464565 TI - [Blood zinc levels in patients with dermatologic and neurologic disorders]. AB - Plasma zinc levels in patients of both sexes suffering from an heterogeneous group of dermopathies were examined and compared with those in patients suffering from psychiatric-neurologic pathologies, in which recent literature has also suggested the role of low zinc levels. The results of the study show a prevalence of effective zinc deficiency in 9.2% of dermatologic patients and 3.9% of neurologic patients, as well as low plasma zinc levels with a different mean, mode and s.d. in comparison to other patients in the control group. These results were statistically significant. The findings are discussed and compared with those reported in the literature. PMID- 8464566 TI - [Electrophysiologic diagnosis of carpal tunnel syndrome in patients with diabetes mellitus]. AB - The authors evaluated 406 patients affected by carpal tunnel syndrome diagnosed by clinical and electromyographic data. Diabetes mellitus was recognized in 57 subjects. The others constituted the control group. The severity of the syndrome was similar in both groups. Also similar was the interval between onset and clinical diagnosis. Such parameters and the severity of the syndrome showed no modification with age in the diabetic group. In the control group, carpal tunnel syndrome was more pronounced in the aged patients, presumably for the longest latency of disease. Carpal tunnel syndrome onset was later in diabetic subjects compared the control. At lastly we found a prevalence of bilaterality in diabetics, and an M/F rate comparable in both groups, as described by other authors. PMID- 8464567 TI - [Preliminary results of a bacteriologic and immunologic study in patients subjected to colorectal surgery]. AB - This study examines patients undergoing colorectal surgery for carcinoma, bacteriological data in faecal and systemic immunological data; these patients before surgery received short-term chemoprophylaxis with ceftriaxone (2 g e.v.) and thymopentina (1 phial/day for 15 days) and after surgery thymopentina (1 phial for three time a week). With these data the authors try to create immunomodulation and antibiotic chemoprophylaxis protocol for the reduction of the septic complications due to intestinal bacterial flora and immunological defence reduction. PMID- 8464568 TI - [Personal experience in the treatment of esophago-cardial stenosis with the Nd YAG laser]. AB - The authors analyze the results of treatment, by Nd-YAG laser. of benign and malignant esophageal and cardial stenoses. Particularly the personal technique, immediate and late complications and association with complementary techniques such as dilatation or intratumoral injection of polidocanol are evaluated. PMID- 8464569 TI - [Ruggero Oddi and the discovery of the common bile duct sphincter]. AB - The author gives some information about life in Perugia in the years 1883-87, when Ruggero Oddi was a medical student at the "Libera Universita" of Perugia. Moreover the author gives notes about the Hospital and the University in those years with special reference to the situation of the Department of Physiology where the discovery of the sphincter of the common bile duct took place. Then, the author reports the most peculiar facts of Ruggero Oddi's life in a chronological way and finally, he deals with the history of Oddi's discovery of the sphincter of the common bile duct, when he was a student in the fourth year at the "Facolta di Medicina e Chirurgia" in Perugia. PMID- 8464570 TI - [Syndrome X and surgical stress. A clinical case]. AB - The syndrome X is a clinical disease characterised by anginous pain with the absence of significant and angiographically visible stenosis of the coronary tree. D. P. M., a 61-year-old woman suffering from biliary lithiasis, underwent cholecystectomy. During the immediate postoperative period, the patient showed difficulty in regaining consciousness and there were electrocardiographic signs of extensive anterior ischemia; prior to the operation only a 1st degree atrio ventricular block and a positive history of occasional precordial pain had been reported. On the 2nd postoperative day the patient complained of violent retrosternal pain irradiated to the left shoulder. Given that the signs of ischemia had regressed, various instrumental tests were performed: echocardiogram, cycloergometric test, dipyridamole test, cold pressure test, Holter's dynamic ECG, all of which were within the normal; moreover, selective coronarography did not reveal significant stenosis of the coronary tree. The patient was therefore diagnosed as suffering from syndrome X. In the light of the present case, the authors conclusion may be summarised as follows: the diagnosis of syndrome X, which is by definition not easy, may sometimes become critical, as in the present case, since rapid intervention would have enabled prophylactic therapy to be performed to combat surgical stress. PMID- 8464571 TI - [Neurological complications in hyperparathyroidism]. AB - The paper describes the clinico-instrumental diagnostic iter in a 57-year-old patient with amyotrophy of the pelvic and pectoral girdles and of the roots of the limbs, with lively and symmetric R.O.T., and without fasciculation, feeling deficit, bulbar involvement and pathological reflexes; EMG was probative for the neurogenic involvement of all four limbs, whereas muscular enzymes were normal. Laboratory controls showed primary hyperparathyroidism caused by a single operated parathyroid adenoma; other test enabled multiple endocrine adenomatosis to be excluded. The paper discusses the involvement of the nervous system during hyperparathyroidism paying special attention to spinal amyotrophy. PMID- 8464572 TI - Past, present, and future of psychiatry in New Jersey. AB - Society faces moral and practical choices of treatment for mental illness: warehousing, neglect, or appropriate treatment. Mental and physical health care must be available to all Americans. There must be a balance between cost containment and patient needs. PMID- 8464573 TI - Psychiatry in the 21st century: evolving diagnostic and therapeutic strategies. AB - Psychiatry has advanced rapidly in the past two decades, with many exciting new developments on the horizon. Today, psychiatry offers more precise diagnoses and an extensive range of effective treatment options. Newer treatment approaches focus on all aspects of psychiatric illness. PMID- 8464574 TI - The psychiatric aspects of HIV/AIDS. AB - The human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) induces a multiplicity of neuropsychiatric symptoms. While some symptoms manifest before acquisition of infection, others become apparent after acquisition of infection. PMID- 8464575 TI - Somatoform disorders: diagnosis and treatment. AB - Somatoform disorders are a group of syndromes in which patients focus on and complain of physical symptoms when there is no demonstrable underlying organic pathology or when complaints are in excess of what is expected. Medical and psychiatric physicians must seek better treatment and diagnosis. PMID- 8464576 TI - Mood disorders: diagnosis and treatment in the 1990s. AB - We all experience fluctuations in mood. There are some persons who experience severe, persistent, or cyclical changes of mood. When this interferes with functioning, it may be a manifestation of those psychiatric illnesses known as mood disorders. PMID- 8464577 TI - Anxiety disorders in the general practice. AB - The author reviews the concept of anxiety and the diagnosis and treatment of panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, social phobia, and post-traumatic stress disorder. The psychiatrist and primary care practitioner can collaborate for the patient's benefit. PMID- 8464578 TI - Differential diagnosis and management of suicidal behavior. AB - Suicidal behavior, like fever and headache, has a differential diagnosis. The physician, confronted with a patient who is suicidal, must identify the etiology of the self-destructive behavior and provide diagnostic-specific treatment. Suicide, in most instances, is a preventable cause of death. PMID- 8464579 TI - What to expect from a psychiatric consultation. AB - The authors present guidelines for psychiatric consultations. The authors emphasize the need for specifics in presenting reasons for psychiatric consultation and/or referral to consultants, and the need for responsive consultation and communication. PMID- 8464580 TI - Frontiers in biological psychiatry: new drug development. AB - This past decade has been a fertile time for new drug developments for the central nervous system. This article discusses cutting edge treatments for depression, anxiety, and psychosis. Some of these medications now are approved; many still are being researched. PMID- 8464581 TI - State HIV-positive physician policy. PMID- 8464582 TI - Detection of contralateral breast cancer by mammography in women with previous breast cancer and the impact of endocrine therapy. AB - AIMS: To determine the efficacy and extent of screening mammography for detection of contralateral breast cancer in a cohort of women with previous unilateral mammary carcinoma, and to assess the effect of endocrine therapy on the risk of developing cancer in the contralateral breast. METHODS: Women with previous breast cancer eligible for mammography were identified from the Auckland breast cancer data file and the extent and outcome of mammographic screening determined by questionnaire and survey of mammography reports. The extent of adjuvant hormonal therapy and development of contralateral breast cancer was ascertained from the ABCDF records. RESULTS: Of 703 eligible subjects, 59% had undergone screening mammography with a cancer detection rate of 17 per 1000 mammograms and a benign to malignant ratio was 1.7 to 1. Contralateral breast cancer developed in 2.9% of 1980 women with previous unilateral mammary tumours who did not receive endocrine therapy with 1.1% of 374 women who were given adjuvant hormonal treatment (p = 0.04). CONCLUSIONS: The efficacy of mammography in those screened was comparable to major overseas screening programs, but the proportion of women undergoing mammography in this high risk group was relatively low suggesting a need for greater promotion of mammography in Auckland. The use of adjuvant endocrine therapy significantly reduced the rate of development of contralateral breast tumours supporting the current development of formal trials of chemoprevention of breast cancer in women at high risk groups of the disorder. PMID- 8464583 TI - Transport and public health. PMID- 8464584 TI - Clinical features of individuals with cystic fibrosis in New Zealand. AB - AIMS: To determine the status of cystic fibrosis patients, their mode of diagnosis and source of medical care in New Zealand. METHODS: A database was established in 1988 to record clinical information on individuals with cystic fibrosis in New Zealand. Three hundred and two cystic fibrosis patients were identified and clinical information on 248 obtained. RESULTS: Thirty five per cent of patients at diagnosis had gastrointestinal and pulmonary and 33% had gastrointestinal symptoms alone. Ninety three infants were diagnosed after a positive screening test and confirmatory sweat test. The mean age at diagnosis overall was 1.8 years, while 61% of children were diagnosed before one year of age. 74.2% of patients were said to be pancreatic insufficient, 4% pancreatic sufficient and in 22% the results were unavailable or unknown. Medical care was provided by 28 sources comprising paediatricians, physicians or combined clinics. One cystic fibrosis clinic cared for more than 40 patients. Sixty-one per cent of cystic fibrosis subjects were colonised with Staphylococcus aureus at some time, and 44% were reported to be colonised with Pseudomonas aeruginosa. CONCLUSIONS: Common clinical features of cystic fibrosis have been characterised for New Zealand patients. It is unknown to what extent the clinical features of the disease and source of medical care in New Zealand are responsible for previously reported survival for the condition but it is planned to examine serial measurements of growth, nutrition, pulmonary function and survival and it is hoped that these measurements will be the subject of a further report. PMID- 8464585 TI - Renal artery stenosis as a cause of heavy albuminuria. AB - We report three cases of heavy albuminuria occurring in hypertensive patients with unilateral or bilateral renal artery stenosis. In two of the patients the albuminuria and hypertension were corrected by removing the ischaemic kidney. The mechanism of the albuminuria, particularly in atheromatous renal artery stenosis, is probably multifactorial. PMID- 8464586 TI - Percutaneous aortic valvuloplasty for aortic stenosis in the elderly. PMID- 8464587 TI - Extracorporeal lung support: an advance in treatment of severe lung disease. PMID- 8464588 TI - Noninsulin dependent diabetes mellitus. PMID- 8464589 TI - Breast cancer and the role of a specialist nurse. PMID- 8464590 TI - ACC assessment for lump sum payment. PMID- 8464591 TI - Tobacco smoking. PMID- 8464592 TI - Tuberculosis in Northland. PMID- 8464594 TI - Turner's syndrome. PMID- 8464593 TI - Activity of cefpodoxime, an oral 3rd generation cephalosporin. PMID- 8464595 TI - Human factors analysis useful for process safety management. PMID- 8464596 TI - Blended east-west medical theories, treatment methods gain acceptance. PMID- 8464597 TI - Industry profile: chemical. A focus on quality prevents worker injury. Interview by Elizabeth Juden Christy. PMID- 8464598 TI - DOT hazmat training rules emphasize employee safety. PMID- 8464599 TI - Proper oxygen use can help save lives in initial medical emergency response. AB - For many people who deal with medical emergencies--some human resource managers, emergency team administrators, CPR and first aid instructors, EMTs, nurses and physicians--the topic of oxygen use by nonmedical responders at the workplace is poorly understood. Workplace emergency response administrators may find it helpful to become familiar with the current emergency medical literature and learn that the previous literature may no longer apply. Furthermore, fear that use of emergency oxygen by nonmedical responders is "playing doctor," and will lead to some imagined uncontrollable catastrophe is based on statistically and medically unfounded misinformation. As is the case with many uncertain events, the perception of risk is unrelated to the actual risk. Refusing to allow appropriately trained nonmedical responders to use reliable emergency oxygen when it is available is a potentially grave error and makes emergency care in the workplace less efficient and valuable. There are many cases of workplace injury or illness in which oxygen use is not only appropriate but may help save a patient's life. Ensuring that the proper emergency oxygen equipment is available where appropriate and properly training personnel are responsible for first aid can, in some cases, lessen the severity of workplace illness and injury incidents. PMID- 8464600 TI - On-site first aid, CPR responders need to make fast, vital decisions. AB - The techniques of first aid and CPR can be learned easily through training programs offered by the American Red Cross and the American Heart Association. Programs designed for all levels of care can be suited to the individual's needs. Basic CPR skills include one rescuer and two rescuer techniques. Adjunct equipment such as pocket masks offer the rescuer protection against possibly infectious body fluids. As the role of the competent person and first responder continue to grow, employers must continue to rely more on the employee to make emergency decisions and administer aid. To ensure effective compliance with the standard and to provide life-saving care, employers must have ready availability of first aid supplies, equipment and trained personnel. Only in this fashion will they be able to ensure timely, adequate care during these critical early moments. PMID- 8464601 TI - The goal of safety training rules: reducing the threat of injury. PMID- 8464602 TI - Reconsideration of the bilaminar zone in the retrodiskal area of the temporomandibular joint. AB - The fibrous connection of the diskal attachment to the condyle and to the surrounding structures, and of the retrodiskal area was investigated histologically. Sections, obtained from six temporomandibular joints with the condyle protruded, were mainly observed. Most of the collagen fibers that compose the posterior band were attached to the condylar poles and to those vicinities behind them, and no diskal attachment was found to the posterior aspect of the condyle. Elastin-rich fibers that originate from the petrotympanic fissure were attached to the disk at the medial end. These fibers had many branches that compose a part of the retrodiskal area and were very wavy in spite of the protruded position of the disk-condyle complex. No other fibers directly connected the disk with the posterior wall of the fossa. Therefore we concluded that there were no upper and the lower strata as termed by Rees. PMID- 8464603 TI - Closed lock. A survey of 400 cases. AB - Four hundred consecutive classic closed lock cases were examined. Of these, 301 were treated. Mandibular range of motion was restored by condylar distraction during jaw opening, anterior, and lateral movements. Mandibular appliances were used to prevent complete closure during healing. Of the 45 males and 355 females examined, almost all reported jaw restrictions, but 38% reported little or no pain. Secondary disorders of temporomandibular joint inflammation, muscle spasm, trigger points, and cervical dysfunction were seen on patients with temporomandibular joint pain. Of the 301 conservatively treated patients, 209 were successfully treated, 55 were moderately successful, and 37 failed. Occlusal factors did not appear as primary etiologic factors. Because all locks were preceded by clicking, treatment is recommended for clicking temporomandibular joint's that lock, however briefly, to prevent future locking. Conservative closed lock treatment is successful in many cases. PMID- 8464604 TI - Avascular necrosis of the mandibular condyle-pathogenesis and concepts of management. AB - A vascular necrosis is a well-recognized pathologic entity in orthopedic surgery which most commonly affects the femoral head. Avascular necrosis of the mandibular condyle has been recognized recently, although controversy exists as to the appropriate methods of diagnosis and treatment. We present a discussion of the pathogenesis of avascular necrosis derived from the orthopedic literature and its extrapolation to management of the temporomandibular joint in the form of decompression corticotomy of the condyle by two techniques. PMID- 8464605 TI - Diplopia caused by orbital floor blowout fracture. AB - Diplopia caused by orbital floor blowout fractures is one of the major complications of orbital injuries. The records of 48 patients who had incurred orbital injuries were reviewed; 23 had a history of a pure orbital blowout fracture. Surgery was indicated when the vertical movement of the eye was impaired, and it was performed after complete resolution of orbital hemorrhage and edema. The maximal time before the first surgical procedure was 14 days. Two patients required a second procedure because of persistent diplopia and enophthalmos. PMID- 8464606 TI - Dimorphic study of surgical anatomic landmarks of the lateral ramus of the mandible. AB - Sixty-three human cadaver hemimandibles of known sexual origin were studied. The anatomic relationship between the midpoint of the waist of the lateral ramus and the mandibular foramen was examined and compared with that of the antilingula. No statistical differences were found between either these two landmarks or the sexes. PMID- 8464607 TI - Efficacy of various surface disinfectants on an irregular surface. AB - Representative samples of hard surface disinfectants were tested against Pseudomonas aeruginosa (ATCC 27853) on frosted glass rods. The same protocol was followed by two investigators on 100 rods for each product tested. Results showed Sporicidin surface disinfectant (Ash Dentsply, York, Pa.) and household bleach 1:10 to be most effective against P. aeruginosa. Lysol disinfectant spray (Lehn & Fink Products, Montvale, N.J.), performed similarly whereas Biocide (Biotrol International, Woods Cross, Utah) failed to inhibit growth on more than half of the rods treated. Failure of the iodophor may be attributed to the use of cotton filled gauze, because cellulose is believed to react with nascent iodine. PMID- 8464608 TI - Dental manifestations of autoimmune hypoparathyroidism. AB - The histopathologic changes in three permanent molars from two siblings with autoimmune hypoparathyroidism as part of candida endocrinopathy syndrome are described. These teeth developed after the diagnosis of hypoparathyroidism and while each subject was receiving vitamin D and calcium supplementation. The pathogenesis of the dental changes is unknown, but it is possible that parathormone may directly influence tooth development independent of its role in calcium and phosphorous homeostasis. PMID- 8464609 TI - Mucormycosis of the oral cavity. AB - Mucormycosis (phycomycosis, zygomycosis) is an acute opportunistic infection caused by a saprophytic fungus found in soil, bread molds, and decaying fruits and vegetables. Numerous predisposing risk factors are associated with mucormycosis, although most cases have been reported in poorly controlled diabetics or in patients with hematologic malignant conditions. This report presents two cases of oral mucormycosis. One case occurred in the maxilla in a patient with well-controlled diabetes. The other involved the mandible and overlying gingiva in a patient with acute myelogenous leukemia. A review of the literature concerning oral mucormycosis is also presented. PMID- 8464610 TI - Oral paracoccidioidomycosis. A study of 36 South American patients. AB - Paracoccidioidomycosis (South American blastomycosis) is an uncommon, progressive systemic mycosis, virtually only seen in persons who have visited Latin America. Reports of oral lesions are extremely rare in the English-language literature. Thirty-six adults with oral lesions as the first sign of paracoccidioidomycosis are described; this appears to be the largest series in the dental literature. All had chronic proliferative mulberry-like ulcerated oral lesions; the diagnosis was confirmed histologically. The gingiva or alveolar process was the typical site, but lesions were also seen particularly on the palate and lip. Most of the patients proved to have detectable pulmonary involvement. Patients with lesions in the oropharynx, tongue, or floor of mouth all had confirmed pulmonary lesions. PMID- 8464611 TI - Mucin-containing lozenges in the treatment of intraoral problems associated with Sjogren's syndrome. A double-blind crossover study in 42 patients. AB - Irreversible hyposalivation is a common sequela of Sjogren's syndrome and may lead to a decreased quality of the patient's life. The aim of this study was to evaluate the efficacy and therapeutic value of mucin-containing lozenges in reducing patients' complaints of hyposalivation. In a double-blind crossover trial in 42 patients with Sjogren's syndrome, the efficacy and therapeutic value of both a mucin-containing and placebo lozenge were assessed by means of self administered questionnaires, which had to be completed before and after the use of each type of lozenge for a period of 2 weeks. Seventy-six percent of the patients preferred the mucin lozenge, 10% preferred the placebo, and 14% had no preference. In reducing patients' complaints, sucking the mucin lozenge resulted in a larger improvement of the total pattern of complaints and the sensation of oral dryness, and in a longer moistening of the oral cavity than the placebo. Oral functioning was improved after the use of the placebo, and the patients reported the taste of the placebo to be better than the mucin lozenge. From the responses it was concluded that the use of the mucin lozenges can be recommended in the treatment of oral symptoms of xerostomia. PMID- 8464612 TI - Histologic study on the metastatic process in the experimental model of lymph node metastasis. AB - The process of lymph node metastasis was studied in an experimental model that was successfully established in our laboratory. The model O-1N carcinoma was transplanted to the buccal pouch of 60 hamsters, and seven or eight hamsters were killed every week from 1 to 8 weeks for histologic examination. At 3 weeks, neoplastic invasion of vascular spaces was demonstrated, and early stage lymph node metastases were seen in five of seven animals. At 5 weeks, lymph node metastases were more advanced, and lung metastasis occurred in one animal. At 8 weeks, lymph node metastases were seen in all eight animals and lung metastases were seen in two of them. Tumor cells initially seen as clusters in afferent lymphatic vessels and in the peripheral sinuses gradually spread to the medulla, replaced the entire lymph node, and extended into adjacent extranodal tissue. The process of metastasis closely resembled that seen in human oral carcinomas. PMID- 8464613 TI - Desmoplastic ameloblastoma. A case report and literature review. AB - The desmoplastic ameloblastoma is a rare histologic variant of ameloblastoma. This article presents a case of desmoplastic ameloblastoma with unique and complex histologic findings. The tumor, which was located in the anterior mandible, was treated by an anterior marginal resection with preservation of the inferior border of the mandible. The clinical, radiographic, surgical, and pathologic aspects of this unusual lesion are presented, and the relevant literature is reviewed. PMID- 8464614 TI - Monoclonal plasmacytic ulcerative stomatitis. A plasma cell dyscrasia? AB - We report a case of extramedullary plasmacytoma that appeared in an uncharacteristic manner as an ulcerative stomatitis affecting particularly the tongue and buccal mucosa. The lesions were associated with a transient lichenoid skin rash. The literature is reviewed and comparisons made between this tumor and the related plasma cell dyscrasias of multiple myeloma and monoclonal gammopathy. PMID- 8464615 TI - Titanium lymph node pigmentation in the reconstruction plate system of a mandibular bone defect. AB - A case of titanium pigmentation that involved a submandibular lymph node is reported. A 41-year old man had been treated for ameloblastoma by partial resection of the mandible followed by reconstruction with the use of a titanium plate to bridge the mandibular defect. Titanium pigmentation occurred in the surrounding soft tissue adjacent to the plate and within a submandibular lymph node 2 years after reconstruction. PMID- 8464616 TI - Oral lichen planus in patients with diabetes. An epidemiologic study. AB - The prevalence of oral lichen planus was studied in 729 persons with diabetes and was found to be in 0.55% of cases. This result was compared with the results obtained from a group of controls without diabetes and from a sample of the general population of similar age and sex distribution. No statistical differences were observed. PMID- 8464617 TI - Taurodontism in premolars. AB - Taurodontism is not a dental anomaly that affects only the molars. In a review of 379 premolars extracted for different pathologic reasons, three cases of taurodontism were found. The three cases were in upper premolars and were studied anatomically and radiographically. The literature was reviewed, as well as the low incidence of the condition in premolars, which is probably related to a genetic condition. Our observations support this fact, as suggested by the study of our cases from a restricted population nucleus, within a district area of the city of Seville, Spain. Among the diagnostic criteria of taurodontism, those established by Shifman and Chanannel are more objective. Finally, our findings support an embryologic origin as a result of a delay in the apical epithelial diaphragm evagination or by interference in the epitheliomesenchymatose induction. PMID- 8464618 TI - Basic technical properties of a system for direct acquisition of digital intraoral radiographs. AB - The Sens-A-Ray system for direct digital intraoral radiography may be used with any computer compatible with an IBM PC/AT. The system relies on a charge-coupled device designed for direct conversion of x-ray energy to an electronic signal. It is the first such device for direct acquisition of radiographs. Technical properties of charge-coupled device detectors when exposed to radiation energies in the range of x-rays used in dental radiography have been studied. Even in the absence of light or x-radiation there is a spontaneous generation of charge within a charge-coupled device detector that gives rise to a background signal, a dark current. It was found that the dark current is a linear function of exposure time. The dose response of the charge-coupled device detector was determined at nominal kilovoltages that range from 50 to 90 kVp. The dose response was shown to be a linear function of exposure. The functions for all kVp settings were practically identical. The charge-coupled device detector is more sensitive to x radiation than conventional dental films and, consequently, its exposure range is more narrow. The signal-to-noise ratio was calculated from the digital radiographs used for the dose response test. The ratio is above 10 for exposures higher than about 2 microC/kg. The line spread function was determined from test radiographs of a 10 microns wide slit in a test object of 1.5 mm thick tantalum. After curve fitting, the line spread function could be expressed as the sum of a Gaussian and an exponential function. Presampling modulation transfer functions valid at the detector plane and at an object plane were calculated from fitted data on the line spread function. It is concluded that the Sens-A-Ray system has such technical properties that it may replace conventional film-based systems. PMID- 8464619 TI - Stray-field imaging (STRAFI) of teeth. AB - During endodontic treatment radiographs are used to get information about the root configurations of the teeth. Another modern imaging system in medicine, magnetic resonance tomography, provides fine pictures of soft tissues without using ionizing radiation. Currently, imaging of bone and teeth cannot be achieved very well by magnetic resonance tomography, therefore in a research experiment a special variant of magnetic resonance microscopy, stray field imaging, was used, which promises new ways of looking into the structure of solids including teeth. Initial experiences in reproducing the outer and inner contours of teeth with this new technique are presented. Limitations and further applications are discussed. PMID- 8464620 TI - Dimensional reproduction in direct digital rotational panoramic radiography. AB - A linear x-ray detector array can be used to perform rotational panoramic radiography provided a technique for data acquisition is used that emulates the dimensional reproduction of a conventional rotational panoramic radiographic system. This may be accomplished with the use of a variable integration time throughout the excursion. The required interval depends upon the scanning geometry, the selected image plane, and the size of pixels used in the digital image. In a prototype device developed around an Orthopantomograph Model OP10 with 0.225 mm square pixels, the integration times range from about 8 milliseconds to 28 milliseconds. An experimental test was performed by radiographing a number of steel spheres positioned at different object depths. Within the limits of experimental error, there was satisfactory agreement between the measured and theoretical magnification. PMID- 8464621 TI - Magnetic resonance imaging of the temporomandibular joint. Value of axial images. AB - The purpose of this study was to determine the value of axial images for diagnosis of disk displacement and osseous changes of the temporomandibular joint. Sagittal, coronal, and axial magnetic resonance images were obtained of 35 fresh temporomandibular joint autopsy specimens. The sagittal and coronal images were interpreted for position of the disk and osseous changes. The value of the axial images for diagnosis of the disk and osseous components was classified into one of four categories: 1) did not add diagnostic information, 2) confirmed findings of sagittal and coronal images, 3) added diagnostic information but did not change the diagnosis, 4) changed the diagnosis. The results showed that the axial images did not add diagnostic information concerning position of the disk in 5 joints, confirmed the diagnosis in 29 joints, and added information but did not change the diagnosis in 1 joint. Concerning osseous abnormalities, the axial images did not add any diagnostic information in 5 joints, confirmed findings of the sagittal and coronal images in 26 joints, added information but did not change the diagnosis in 3 joints and changed the diagnosis in 1 joint. On the basis of these results, it is concluded that the axial plane of imaging of the temporomandibular joint is of relatively little value for assessment of disk displacement and osseous changes. Axial imaging is therefore not recommended for diagnosis of disk position and osseous abnormalities. PMID- 8464622 TI - A misleading pharyngeal swelling. PMID- 8464623 TI - Wiskott-Aldrich syndrome, renal failure, and osteosclerosis. PMID- 8464624 TI - Hypoplastic neural arch: an anomaly of the first cervical vertebra. PMID- 8464625 TI - Aspiration of two dental units resulting from a motor vehicle accident. PMID- 8464627 TI - [Surgical management of congenital high vaginal atresia]. AB - In the past 15 years five neonates and children have been treated for high vaginal atresia at the Surgical Unit of Department of Pediatrics, University Medical School, Pecs, Hungary. In three of the six patients distal atresia of the vagina was found (Type III). Two of the three were neonates and had a large hydrometrocolpos and the third, a 13-year-old girl, hematometrocolpos. In the fourth patient the vaginal atresia was associated with cloacal and anorectal malformation (Type V). In the fifth there was a duplication of uterus and vagina; however, only one of the two vaginas was atretic. In three patients a pull through of the vagina was carried out, in one of them according to Pena, in another a transvesical approach, as suggested by Monfort, was used. Following repeated surgeries in the patient with cloacal malformation the vagina was replaced with large intestine. In the case of duplication of vagina and uterus one half of the duplication was removed. PMID- 8464626 TI - [PGI2-like activity of the internal mammary artery and the saphenous vein used in coronary bypass surgery]. AB - The best graft in coronary bypass operations is the internal mammary artery as its rate of staying open for long term is better than that of saphenous vein. The prostacyclin-producing capacity of these human blood vessels was studied using platelet aggregation bioassay. The synthesis of prostacyclin-analogous was significant higher in internal mammary artery than that was in saphenous vein (in 10 min of incubation time internal mammary artery: 73.33; saphenous vein: 42.27 pg/mg). Based on our results we conclude that the difference of "prostacyclin like" activity between artery and vein might play a role, at least partly, in the more successful operations performed with internal mammary artery. PMID- 8464628 TI - [Allergic inflammatory markers in upper respiratory allergies]. AB - The inflammatory mediators of allergy were investigated in symptomatic patients suffering from upper respiratory tract allergy. The serum tryptase level as an indicator of mast cell activation and serum eosinophil cationic protein level as an indicator of eosinophil activation were measured. They did not find any alteration in the serum level of tryptase. The level of eosinophil cationic protein significantly increased in symptomatic patients comparing to normal healthy controls. There was not any correlation to the severity of symptoms and to the absolute eosinophil count in the peripheral blood. The different activation possibilities of the eosinophil granulocytes are discussed, highlighting the role of Th2-helper lymphocytes. PMID- 8464629 TI - [Dopamine, noradrenaline and serotonin levels in amniotic fluid during the second trimester in normal and pathologic pregnancy]. AB - Authors measured the dopamine (DA), noradrenaline (NA) and serotonin (5-HT) contents of amniotic fluid between 19 and 21 weeks with fluorimetric method. The amniotic fluid samples were obtained by transabdominal amniocenteses performed due to elevated maternal serum-alphafetoprotein levels and suspect ultrasound findings. They considered as normal values the average of 30 amniotic fluid samples obtained from pregnant women who gave birth to healthy babies at term. The mean values (mean+SE) of normal cases were 136.6 + 20.2 nmol/l for DA, 29.5 + 9.4 nmol/l for NA and 72.6 + 4.9 nmol/l for 5-HT. Against these values, in cases of open spina bifida the level of NA showed no significant difference, the DA level was higher (p < 0.05) and the 5-HT level was also higher (p < 0.001). The DA level was found higher (p < 0.05) in cases of intrauterine retardation as well, however there was no difference in the NA and 5-HT levels in these cases. In cases of preterm deliveries, none of the above parameters showed differences. Authors suggest that in cases of spina bifida the measurement of 5-HT in the amniotic fluid can be a complementary diagnostic method. They also state that no prognosis about the outcome of pregnancies can be expected from such examinations. PMID- 8464630 TI - [Clinico-pathological and orthopedic-surgical aspects of essential osteolysis (Gorham disease)]. AB - Authors present two cases. One of their patient was followed for 30 years. They discuss the pathological characters and diagnostic difficulties of the disease. They have observed that with radical operations of--according to necessity- serial surgical interventions the outcome of patients can be properly controlled against recent pessimistic opinions. PMID- 8464631 TI - [Mineral baths and medicine in Hungary in the 13th-15th centuries]. PMID- 8464632 TI - Mandible fractures--medical and economic considerations. AB - This article retrospectively evaluates 1278 mandibular fractures and compares intermaxillary fixation, plating, and interosseous wiring as to outcomes and cost effectiveness of treatment. The predominance of young men with personal altercations reflects the urban patient setting. The infection from plating exceeds other methods and this difference is also reflected in increased patient days (in the hospital) and an increased length of time for postoperative care. No significant differences are observed between treatments for non-union, malunion, facial nerve injury, or temporal mandibular joint problems. Other factors, such as site and severity of injury and experience of the surgeons are considered. Cost implications are important, but should be just one factor in evaluation for the best treatment for each patient. PMID- 8464633 TI - Predicting long-term facial nerve outcome after acoustic neuroma surgery. AB - Although anatomic preservation of the facial nerve is achieved in nearly 90% of reported cases after acoustic neuroma surgery, postoperative long-term facial function is of most concern to the patient. This study examines long-term facial nerve function in relation to the immediate postoperative function and the function at time of discharge from the hospital. Subjects included 515 patients who underwent primary acoustic neuroma removal at House Ear Clinic from 1982 through 1989 and who had normal preoperative facial function, an intact facial nerve after surgery, and a House-Brackmann facial nerve grade available immediately postoperatively, at time of hospital discharge, and at least 1 year postoperatively. Rate of acceptable facial function (House grades I-IV) differed significantly (p < or = 0.001) at the three postoperative time intervals: 85.2%, immediate; 73.6%, discharge; 93.8%, long-term. Of those with good immediate function (grades I-II), 98.6% had acceptable long-term function. Of those with poor immediate function (grades V-VI), 69.8% had acceptable long-term function. We conclude that facial nerve recovery after acoustic neuroma surgery is characterized by slight deterioration in the immediate postoperative period, but subsequent improvement in the long-term. Patients can be reliably counseled that acceptable function immediately after surgery is associated with a favorable long term outcome; poor function immediately after surgery, despite an intact nerve, has a more guarded prognosis. PMID- 8464634 TI - Epidermoid carcinoma of the oral cavity and oropharynx: validity of the current AJCC staging system and new statistical tools for the prediction of subclinical neck disease. AB - The 1983 and 1988 AJCC T- and N-staging systems were compared using the case records of 531 patients with primary epidermoid malignancies of the oral cavity. All patients had a minimum followup of 5 years. There were 390 patients with early stage (T1, T2) disease and 141 with advanced stage (T3, T4) lesions according to both the 1983 and 1988 T-definitions: 342 patients manifested no clinical nodes (NO), 189 had clinically evident nodes (N1-N3), and none had metastatic disease. Cox regression analysis demonstrated that the 1983/1988 T stage definitions differentiated survival successfully (p < 0.001). The 1988 staging system for nodal disease showed a highly significant separation of N2 and N3 when compared with the 1983 system (p < 0.001). Of the 342 patients who were staged N0, 154 had primary neck dissection. Logistic regression predicted the incidence of subclinical disease according to the site and the T-stage of the primary tumor with a sensitivity of 78% and a specificity of 95%. We conclude that the 1988 N-stage definition is a better prognosticator of survival than the 1983 definition. Furthermore, a logistic regression model can be used to predict the probability of subclinical disease in primary oral cavity cancers. PMID- 8464635 TI - The synergistic effects of rhodamine-123 and merocyanine-540 laser dyes on human tumor cell lines: a new approach to laser phototherapy. AB - Many new photosensitizers and laser wavelengths are being tested to improve photodynamic therapy by enhancing specific tumor uptake and/or retention, lowering systemic toxicity, and increasing laser tissue penetration. In this study the potential synergistic effects of rhodamine-123 (Rh-123) and merocyanine 540 (MC-540) sensitization of human tumor cell lines after laser exposure were explored. In a first series of experiments, the kinetics of uptake of Rh-123 and M-540 were tested on three human leukemia cell lines (K562, RAJI, 729HF2), P3 squamous carcinoma, and M26 melanoma. Our results demonstrate a clear difference in the rate and amount of uptake of MC-540 (K562 > P3 > RAJI > 729HF2 > M26) and Rh-123 (P3 > RAJI > 729HF2 > K562 > M26) by these cell lines. In a second series of experiments, M26 tumor cells were sensitized with either Rh-123 (1 microgram/ml) or with MC-540 (20 micrograms/ml) alone or with a combination of the two dyes for 60 minutes, then exposed to the argon (514.5 nm) laser at nonthermal energy levels. Our results demonstrate a significant enhancement of the tumoricidal effects of the laser on M26 carcinoma cells after sensitization with both dyes together (MC-540 and Rh-123) when compared to each dye alone. As with combination antibiotherapy, the synergistic effects of two laser dyes that have different intracellular targeting sites appear to enhance tumoricidal effects significantly after exposure to a matching laser wavelength. The data provide evidence for effective laser phototherapy by dye synergy. PMID- 8464636 TI - Intraoral ultrasonography in the diagnosis of peritonsillar abscess. AB - The diagnosis of quinsy is traditionally established on the basis of clinical observations and sometimes several diagnostic punctures. The present study has focused on the possible usefulness of intraoral ultrasonography (IOU) as a diagnostic tool when a peritonsillar abscess is suspected. The results show that it is possible to demonstrate, with a high degree of accuracy, the presence of an abscess, its volume, location, and its relation to the carotid artery. With this information an exact and safe diagnostic puncture can be performed when necessary and avoided in cases with clinical signs of quinsy with no abscess. PMID- 8464637 TI - Leukocyte esterase activity in effusion fluid of patients with otitis media. AB - Fluid obtained during myringotomy and tube placement in 20 patients with middle ear effusions was assayed for leukocyte esterase activity using a quantitative spectrophotometric assay. This quantitative assay used the synthetic substrate, N tosyl indoxyl alaninate. Seven of the 20 samples showed no measurable enzyme activity (8 U/ml or less). The remaining samples demonstrated activity ranging from 20 to 1600 units. Although enzyme activity did not correlate well with the physical appearance of the fluid, it did correlate with clinical history, suggesting the presence of a purulent exudate rather than serous effusion. Leukocyte esterase activity in the fluid appears to hold promise as an indicator for the presence of chronic middle ear infection. The enzyme can be assayed by a simple and fast diagnostic strip test, with results available almost immediately. PMID- 8464638 TI - Hearing levels of patients with otosclerosis 10 years after stapedectomy. AB - Hearing levels of 174 patients (213 ears operated on) with otosclerosis undergoing stapedectomy were analyzed. All patients had followup of 10 years or more, the mean follow-up period being 13.4 years. Eighty-seven ears (41%) underwent posterior crus stapedectomy, and in the remaining 126 ears (59%) a prosthesis was inserted. Large fenestra technique was used in all cases. In the long run, both air conduction and bone conduction thresholds of ears operated on showed remarkable deterioration from the best values obtained 6 to 12 months postoperatively. Ten years after surgery both air conduction and bone conduction thresholds of ears operated on were significantly worse than those of normal controls. At 10 years, 70 percent of the ears operated on had hearing levels (at 0.5 to 2.0 kHz) of 30 dB or better and 88 percent had 40 dB or better. At the last follow-up examination, in 90% of the patients the better hearing ear had a hearing level of 40 dB or better. In 90% of patients with bilateral otosclerosis who had operations in only one ear, the ear operated on had better hearing function than the opposite ear that had not been operated on. PMID- 8464639 TI - Partial thyroarytenoid myectomy: an animal study investigating a proposed new treatment for adductor spasmodic dysphonia. AB - A new surgical procedure with potential application for the treatment of adductor spasmodic dysphonia was performed on ten rabbits to assess surgical effects on laryngeal function. Using an external approach, partial unilateral thyroarytenoid (TA) muscle excision was performed through a thyroplasty cartilage window. The contralateral side was left undisturbed as a control. The animals were studied acutely and at 3 months using videolaryngoscopy. Electrophysiologic measurements were recorded at 3 months. The procedure was well tolerated by all animals, with no postoperative infection or aspiration. At 3 months, spontaneous and evoked (recurrent laryngeal nerve stimulation) TA muscle electromyographic potentials were measurable bilaterally. TA compound muscle action potential amplitudes were reduced on the side of myectomy. The threshold of recurrent laryngeal nerve stimulation needed to produce observable vocal fold adduction was increased on the side operated on. Perioperative and long-term (3 months) videolaryngoscopy demonstrated preservation of laryngeal competence with good true vocal cord adduction. Histologic analysis with whole organ sections showed replacement of excised muscle with loose fibroareolar tissue. No evidence of muscle regeneration was observed. The vocal ligament and vocal fold mucosa were intact and undistorted in all specimens. This procedure is technically simple and appears to effectively result in a functional yet weakened TA muscle. Because myectomy includes motor unit end-plate excision, problems associated with reinnervation may be circumvented. TA myectomy may be applicable in patients with focal laryngeal dystonia to decrease muscle spasm. PMID- 8464640 TI - Short latency vestibular evoked potentials. AB - Auditory responses, including the well-characterized auditory brainstem response, have been used extensively in clinical investigations. Evoked responses have not been adequately developed to investigate the vestibular system. The purpose of this study is to describe a new method for the evaluation of short-latency vestibular evoked potentials in human subjects. Standard ABR equipment is used, with a customized solid-state modification of the triggering mechanism. Signal averaging is used to record responses to multiple linear decelerations. Results indicate the presence of a short-latency wave, which is absent in vestibular deficient subjects. The literature is reviewed and illustrative cases are presented. We believe vestibular evoked potentials are a promising new modality in investigation of vestibular physiology. PMID- 8464641 TI - Subtotal petrosectomy in the management of advanced parotid neoplasms. AB - Circumferential growth of parotid neoplasms may involve the external auditory meatus posteriorly, the floor of the middle cranial fossa superiorly, and the neurovascular structures of the jugular foramen medially. Inadequate tumor resection in these anatomically complex regions will result in local disease recurrence at the lateral skull base. A subtotal petrosectomy approach has been combined with a standard total parotidectomy in the management of 27 patients with aggressive parotid tumors. Twenty-two patients had malignant lesions and 10 individuals had recurrent disease. The resultant conductive hearing loss is outweighed by the following advantages of this technique: (1) the ability to obtain tumor-free bony margins, (2) proximal intratemporal facial nerve identification, (3) vascular control of the jugular bulb and petrous carotid artery, and (4) the dissection and protection of cranial nerves IX through XII. Our series of 27 patients will be detailed with an emphasis on surgical technique and overall patient results. PMID- 8464642 TI - Indications and results of cordectomy for early glottic carcinoma. AB - Select early glottic carcinomas in patients with normal vocal cord mobility can be successfully treated with cordectomy, performed either endoscopically or by means of an open operation (laryngofissure-cordectomy). From 1976 to 1986, 95 patients underwent cordectomy at our institution. There were 88 men and 7 women, with an age range at the time of surgery of 27 to 84 years. A laryngofissure was used to perform a cordectomy in 61 patients and an endoscopic approach was used in 34. The median number of days in the hospital for the endoscopic group was 2, and for the laryngofissure group it was 6. The Kaplan-Meier product-limit method showed the probability of no recurrence in the first 3 years after an endoscopic cordectomy was 0.9099, and in the laryngofissure-cordectomy group it was 0.9502. To date, there have been four recurrences (11.8%) in the endoscopic group and three (4.9%) in the laryngofissure group. Only one patient with recurrent tumor is known to have died of the cancer. Laryngectomy was necessary for ultimate control in three patients. The Kaplan-Meier survival curve for the 95 patients was the same as that for a sex- and age-matched control group. Cordectomy is an effective treatment option that results in minimal morbidity for select early glottic carcinomas. PMID- 8464643 TI - Wound healing of KTP and argon laser lesions in the canine nasal cavity. AB - The potassium titanyl phosphate (KTP) and argon lasers are increasingly used in nasal and sinus surgery. Histologic effects of these lasers on living nasal tissue have not been investigated. Sixteen dogs underwent laser nasal surgery (eight for each laser). Flexible fiberoptic quartz fibers were used with both lasers to deliver the laser energy to the tissue. The dogs were allowed to heal and then underwent biopsy at 3, 7, 21, and 90 days postoperatively. The argon and KTP lasers had similar tissue effects. Histologically, a thin rim of coagulation necrosis and acute inflammation were seen at 3 days postoperatively. By 7 days, fibroblasts and granulation tissue were observed. At 21 days, fibroblast proliferation and re-epithelialization with respiratory epithelium were the predominant findings. Finally, at 90 days postoperatively, respiratory epithelium and submucosal structures were found overlying a plug of scar filling the defect in the septal cartilage. This healing was consistent through a wide range of energy densities. These lasers are easily used with sinus endoscopes and the operating microscope to allow access to difficult areas. These factors and the wound-healing characteristics noted in this study would seem to make them suited for use in rhinologic surgery. PMID- 8464644 TI - Osteoma of the internal auditory canal. AB - The use of MRI for the evaluation of lesions in the internal auditory canal presents a potential pitfall in the diagnosis of bony lesions of the IAC, because bone is poorly visualized with this method of imaging. The presence of marrow in an osteoma might aid in its detection, since fat in the marrow has a bright signal intensity of T1-weighted imaging. Computed tomography remains the imaging modality of choice for bony lesions of the temporal bone. We demonstrate a case of IAC osteoma in which surgical removal resulted in improvement of symptoms. The gross and microscopic appearance of the IAC osteoma in this case is similar to the characteristic findings of osteomas of the EAC. This suggests that the criteria applied to osteomas and exostoses of the EAC may also be used to differentiate bony lesions of the IAC. PMID- 8464645 TI - Bilateral facial paralysis related to sexually transmitted herpes simplex: clinical course and MRI findings. PMID- 8464646 TI - A pediatrician's view. Choosing the right antibiotic. PMID- 8464647 TI - Antibiotic update. Introduction. PMID- 8464648 TI - Cefprozil. AB - Cefprozil is a new, orally bioavailable, cephalosporin with significant activity against the bacteria commonly associated with upper and lower respiratory tract infection, and skin and soft tissue infections. Its absorption and elimination dynamics suggest once- or twice-daily dosing. The low-rate of gastrointestinal and dermatologic side effects associated with cefprozil administration suggest that it may have a significant role in the management of patients with these infections. Children with pharyngitis or urinary tract infection are more appropriately treated with antibiotics having a narrower spectrum of activity. With a variety of newer cephalosporins being marketed in the early 1990s, it will be important for the clinician to examine the data from ongoing comparative clinical trials to determine which antibiotic is best for a patient with a specific infection and whether the added cost justifies its use. PMID- 8464649 TI - Cefixime. PMID- 8464650 TI - Cefpodoxime proxetil. PMID- 8464651 TI - Ampicillin-sulbactam. PMID- 8464652 TI - The American Pediatric Society 103rd annual meeting and the Society for Pediatric Research 62nd annual meeting. Washington, D.C., May 3-6, 1993. Abstracts. PMID- 8464653 TI - Beyond pediatrics: the health and survival of disadvantaged children. E. H. Christopherson lectureship on international child health. PMID- 8464654 TI - Sydenham's chorea: physical and psychological symptoms of St Vitus dance. AB - Eleven children with Sydenham's chorea (8 girls and 3 boys, mean age = 8.4 +/- 2.2 [SD] years) underwent comprehensive physical, neuropsychologic, and psychiatric examination. The chorea was manifested as dysarthria, gait disturbances, and frequent adventitious movements of the face, neck, trunk, and extremities. Antineuronal antibodies were present in 10 of 11 children. All children exhibited concomitant psychologic dysfunction, specifically obsessive compulsive symptomatology, increased emotional lability, motoric hyperactivity, irritability, distractibility, and age-regressed behavior. Obsessive-compulsive symptoms were observed in 9 (82%) children, 4 of whom met diagnostic criteria for obsessive-compulsive disorder. These behavioral symptoms began several days to weeks before the chorea was observed, and they waxed and waned in severity along with the motoric abnormalities. These results suggest that psychologic, particularly obsessive-compulsive, symptoms are accompanying manifestations of Sydenham's chorea which may require medical attention. PMID- 8464655 TI - Cardiovascular abnormalities in children with fragile X syndrome. AB - It has been suggested by several authors that the prevalence of mitral valve prolapse and aortic root dilation is increased in individuals with the fragile X syndrome. The prevalence of these abnormalities in young children with fragile X has not been established. Sixteen boys and 1 girl 13 years or younger were studied. Only 1 child (6%) had the typical examination findings of mitral valve prolapse, although his echocardiogram was normal. From this study it appears that cardiac abnormalities in fragile X syndrome develop in late childhood and adolescence. It seems important to follow these children carefully so that these cardiac abnormalities can be documented when they do develop. PMID- 8464656 TI - Long-term results of treatment with low-dose fluoxymesterone in constitutional delay of growth and puberty and in genetic short stature. AB - This prospective study was designed to assess growth response, side effects, other possible long-term effects, and final adult height in boys treated with the oral androgen, fluoxymesterone. From 1973 to 1984, eighty-two short boys (71 with constitutional delay of growth and puberty [CDGP] and 11 with genetic short stature [GSS]) were treated with daily oral doses of 2.5 mg of fluoxymesterone from 6 to 60 months. Final height assessment was made from 1989 to 1991. A group of 34 untreated boys (26 with CDGP and 8 with GSS) were also followed to assess the accuracy of the Greulich-Pyle and Bayley-Pinneau (GP-BP) and sexual maturity index height prediction methods. During treatment, each patient had a 1.7- to 2.5 fold increase in linear growth velocity. Accelerated velocity (over baseline) continued as long as the bone age was less than 14 years. No adverse androgenic effects (or undue acceleration of puberty) were observed. Final height exceeded pretreatment predictions for CDGP + GSS by 6.1 +/- 3.5 (SD) cm (GP-BP) and 5.4 +/ 3.2 cm (sexual maturity index). It is concluded that a daily oral dose of 2.5 mg of fluoxymesterone can be used to accelerate linear growth in boys with CDGP and GSS when needed to alleviate emotional problems secondary to slow growth and short stature without fear of compromising final adult height. PMID- 8464657 TI - Blunt trauma in children: causes and outcomes of head versus extracranial injury. AB - A subset of the National Pediatric Trauma Registry was analyzed to describe causes and outcomes of blunt trauma among children younger than age 15 years. This subset, of 8639 children with blunt trauma, was divided into three groups according to the injured body region: a group with extracranial injury only (ECI) accounted for one half of the population, and the remainder were equally distributed between a group with head injury only (HI) and one with both conditions (ECI + HI). The three groups were compared with respect to demographic characteristics, external cause of injury, injury severity, and outcomes. Falls were the leading cause of injury in the HI group, where children were younger, whereas traffic-related injuries predominated in children with ECI or ECI + HI. Pedestrian injuries accounted for a significant share of poor outcomes. The highest proportions of deaths and severe injuries were observed in the mixed group (ECI +HI), and the lowest, in the ECI group. In contrast, functional impairments at discharge were most frequently noted in the ECI group, where 60% of the children were discharged with at least one impairment. While only 6% of children with HI were discharged with impairment, those affected exhibited more deficits in cognition and behavior, which are expected to persist longer than dysfunction in activities of daily living. PMID- 8464658 TI - Management of cardiopulmonary and trauma resuscitation in the pediatric emergency department. AB - The etiology and management of critical illness and injury in a pediatric emergency department were reviewed to survey the use of cardiopulmonary and trauma resuscitation and to compare these data with the educational content of Pediatric Advanced Life Support (PALS) courses. The emergency department records of 183 patients treated in the cardiopulmonary/trauma resuscitation room of a pediatric emergency department over a 17-month period were reviewed for data on diagnosis, morbidity, presence of apnea or pulselessness, and utilization of several resuscitation skills: intubation, cardioversion, tibial interosseous line placement, and other resuscitation techniques. Apneic and pulseless pediatric patients had poor survival (10.3%), but apneic patients had excellent survival (96.9%). Endotracheal intubation (57.9%), bag-valve-mask ventilation (63.9%), and medications for rapid-sequence induction of anesthesia prior to endotracheal intubation (25.7%) were used frequently. Inasmuch as asystole was the most common rhythm in pulseless patients, cardioversion and defibrillation were rarely used (2.2%). Specialized vascular access techniques, tibial interosseous lines (24.0%), and femoral intravenous lines (19.7%), were used frequently in pediatric patients. The frequent use of airway management skills and the excellent survival of apneic pediatric patients supports the current emphasis on airway management in PALS courses. Cardioversion/defibrillation should receive less emphasis in PALS courses. The frequent use of rapid-sequence induction of anesthesia prior to endotracheal intubation indicates that these techniques might warrant increased emphasis in the training of pediatric emergency department personnel and in PALS courses. PMID- 8464659 TI - Human immunodeficiency virus-infected adolescents: the first 50 patients in a New York City program. AB - To address the unique manifestations of human immunodeficiency virus (HIV) among adolescents aged 13 through 21 years, a comprehensive evaluation and treatment program for high-risk and HIV-positive adolescents was developed in New York City in 1987. Among HIV-infected youth, mean age of testing was 18.2 years. One third of the HIV-positive patients were female and four fifths were African-American or Hispanic. No significant differences were found between HIV-positive (n = 50) and HIV-negative (n = 43) patients for age at first intercourse, injecting or other illicit drug use, history of sexually transmitted diseases, or survival sex (exchange of sex for money or drugs). HIV-positive males were more likely than HIV-negative males to have engaged in anal intercourse and to report a history of sexual abuse. Among infected females, 82% acquired HIV through heterosexual intercourse. Almost half (48%) of HIV-positive adolescents had significant immune dysfunction at the time of their initial visit (CD4 < 500/mm3) and were eligible for zidovudine. Many HIV-positive adolescents continued high-risk behaviors such as intercourse without condoms, particularly those with ongoing dependence on drugs or alcohol. With the epidemic of HIV infection increasing nationwide among adolescents, specialized, comprehensive programs are needed to counsel and treat HIV-infected adolescents and youth in high-risk situations. PMID- 8464660 TI - Neurologic history and examination results and their relationship to human immunodeficiency virus type 1 serostatus in hemophilic subjects: results from the hemophilia growth and development study. AB - In a prospective study of the growth and neuropsychologic function of hemophilic subjects, 333 boys, median age of 12.3 years, had baseline neurologic examinations. The study population included 207 individuals (62%) who were seropositive for human immunodeficiency virus type 1 (HIV-1). Overall results indicated that 11% had abnormalities of cranial nerve function, 17% had abnormal deep tendon reflexes, 23% had abnormal strength, 25% had abnormal coordination, and 31% had abnormal tone, bulk, or range of motion. By contrast, 2% or fewer displayed abnormal movements or had abnormal pain or vibratory sensation, or altered mental status. Abnormalities were more common in older hemophilic subjects (eg, 67 [38%] of 177 subjects > or = 12 years of age had abnormal tone, bulk, or range of motion vs 36 [23%] of 156 subjects < 12 years of age). When compared with regard to HIV-1 status, HIV-seronegative and HIV-seropositive subjects did not differ with regard to head circumference or the frequency of abnormalities of cranial nerve function, sensation, muscle strength, or coordination. However, deep tendon reflexes and tone, bulk, or range of motion were more frequently abnormal in HIV-1-seropositive individuals. More HIV-1 positive subjects had at least one increased deep tendon reflex (13/207 [6.3%] vs 1/126 [0.8%] in seronegatives) and more had non-hemophilia-related decreases in muscle bulk (7/207 [3.4%] vs 0/126 in seronegatives). These results indicate that hemophilia causes substantial neurologic dysfunction and that certain findings, such as changes in muscle-stretch reflexes or muscle bulk, may also reflect the neurologic consequences of HIV infection. PMID- 8464661 TI - The bicycle: a developmental toy versus a vehicle. AB - This study was designed to compare bicycle-motor vehicle collisions involving those children using the bicycle for play vs those using it for transportation. Data were obtained from a multihospital-based monitoring system of traffic related injuries among children aged 0 through 14 years, including the coroner's office, in a single urban county. The sample consisted of 289 children through 14 years of age; 123 (43%) were playing; 166 (57%) were on a purposeful trip. Those playing were younger; closer to home; on residential streets with fewer traffic lanes, lower posted speed limits, and lighter traffic; and more frequently with other children. Those using the bicycle for transportation or for a purposeful trip were more commonly 10 to 14 years of age, riding on multilane streets, and riding alone. Forty-five percent of these children were en route to/from school. There were no significant differences between the two groups with respect to number, severity, or distribution of injuries. Extremity and head injuries were predominant. This study demonstrates that motor vehicle-bicycle injuries among young children bicycling in their own neighborhood are just as severe as those in older children who are using the bicycle as a means of transportation. Recommendations for interventions include establishing an appropriate age at which children are permitted to bicycle in the street, separating bicyclists from traffic, teaching bicyclists the rules of the road, consideration of licensure, and use of helmets. PMID- 8464662 TI - Safety and immunogenicity of an acellular pertussis vaccine booster in 15- to 20 month-old children previously immunized with acellular or whole-cell pertussis vaccine as infants. AB - The objective of this study was to evaluate reactogenicity and immunogenicity of the recently US-licensed Connaught/BIKEN (C/B) acellular DTP (ADTP) vaccine as a booster for children aged 15 to 20 months after they had received either the C/B ADTP or the US-licensed Connaught whole-cell DTP (WDTP) vaccine as infants. After infants had received either three doses of C/B ADTP (n = 109) or three doses of WDTP vaccine (n = 30) at 2, 4, and 6 months of age according to a 3:1, randomized, prospective design, they all received booster doses at 15 to 20 months of age with C/B ADTP. Fever > 101 degrees F (38.3 degrees C), irritability, injection site redness > or = 1 inch, injection site swelling, and injection site pain, among other reactions, were monitored for 14 days after vaccination. IgG antibody to pertussis toxin (PT) and filamentous hemagglutinin were analyzed by enzyme-linked immunosorbent assay and neutralizing antibody to PT was measured by Chinese hamster ovary (CHO) cell assay. No significant differences were observed between the WDTP- and ADTP-primed infants following their ADTP booster for any of the monitored reactions within 72 hours of vaccine administration or in the 4 to 14 days after vaccination. Prior to the ADTP booster, antibody levels were higher in children who had received ADTP compared with those who had received WDTP vaccine as infants for PT antibody as measured by enzyme-linked immunosorbent assay and CHO cell assay. Higher levels of IgG antibody following the ADTP booster were observed to filamentous hemagglutinin and to PT in ADTP-primed compared with WDTP-primed children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464663 TI - Oscillometric blood pressures in the arm, thigh, and calf in healthy children and those with aortic coarctation. AB - Comparing blood pressure (BP) obtained in the arm with that obtained in the thigh or calf is important in the diagnosis of aortic coarctation. However, normative mean and range of differences in BP between the arm and lower extremity sites are not available for normal children. It is also not known how accurately the differences in BP between the arm and the lower extremity sites predict the pulsed Doppler estimation of systolic pressure (SP) gradient across an aortic coarctation. To resolve these questions, the authors obtained two BP measurements by an oscillometric (Dinamap) method in the arm, thigh, and calf in 74 healthy children aged 4 to 16 years. Oscillometric BP was also obtained in 21 children aged 3 to 17 years with preoperative or postoperative aortic coarctation and BP gradients were compared with that estimated by the pulsed Doppler method. Overall, SP was higher in the thigh and calf than in the arm. The gradients in SP expressed as arm SP minus calf SP [S(A-C)] and arm SP minus thigh SP [S(A-T)] were significantly greater in children 4 through 8 years old than in those 9 to 16 years old. The S(A-C) was -9.3 (+/- 7.4 SD) mm Hg in the 4- through 8-year group and -5.0 (+/- 6.9 SD) mm Hg in the 9- to 16-year group. The S(A-T) was -7.1 (+/- 6.8 SD) mm Hg in the 4- through 8-year group and -2.4 (+/- 7.7 SD) mm Hg in the 9- to 16-year group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464664 TI - Does prolonged breast-feeding impair child growth? A critical review. AB - Recent epidemiologic evidence suggests that children in developing countries who terminate breast-feeding before their first birthday are less likely to be malnourished than those who are breast-fed for longer durations. This finding calls into question the advice women are given to breast-feed as long as possible. This review examines several studies that found a relationship between prolonged breast-feeding and malnutrition. Many studies have shown a negative association between prolonged breast-feeding and growth, but there is little reason to expect the association to be causal. Problems in study design and analysis, such as failure to control for confounding and reverse causality, leave the nature of the association largely unspecified. PMID- 8464665 TI - Evaluation of a promotional strategy to increase bicycle helmet use by children. AB - Bicycle-related head injuries are an important cause of death and disability, despite the availability of helmets. The objective of this study was to evaluate the effectiveness of a school-based bicycle helmet promotion program in increasing helmet use by children while controlling for secular trends. Two high income and two low-income schools in an urban Canadian community were selected to receive a bicycle helmet promotion intervention, with the remaining 18 schools serving as controls. Approximately 1800 observations of bicycling children were made at randomly selected observational sites 2 to 5 months after the intervention to assess changes in behavior. Helmet use at all observation sites tripled from 3.4% (1990, preintervention) to 16% (1991, postintervention). In the high-income intervention area, observed helmet use rose dramatically from 4% to 36% in contrast to the more modest increase in the high-income control area from 4% to 15%. In the low-income intervention area, there was a modest increase from 1% to 7%, but it did not differ from the increase in the low-income control area from 3% to 13%. The program was highly successful in children of high-income families but not in children of low-income families. Developing strategies for low-income families remains a priority. PMID- 8464666 TI - Neurobehavioral profiles of neonates exposed to cocaine prenatally. AB - This study examined the effects of maternal cocaine use on performance on the Neonatal Behavioral Assessment Scale (NBAS). Cocaine-exposed newborns (n = 56) were compared with a non-cocaine-exposed group (n = 30) born to mothers with similar sociodemographic characteristics. Cocaine-exposed newborns showed significant reduction in birth weight but did not experience greater obstetric or postnatal complications. On neurobehavioral assessments using the NBAS, cocaine exposed newborns showed significantly depressed performance on the habituation cluster but not on other NBAS clusters when differences in birth weight were controlled. In a sample of 30 cocaine-exposed newborns matched on birth weight, gestational age, and race to the 30 non-cocaine-exposed newborns, cocaine-exposed newborns continued to show depressed habituation performance. The significance of a selective effect of cocaine exposure on early habituation performance is discussed in terms of the implications for attentional regulation in the first year of life. PMID- 8464667 TI - Influence of thumb sucking on peer social acceptance in first-grade children. AB - Chronic thumb sucking in school-age children may reduce peer social acceptance, an important contributor to social development. The influence of thumb sucking on social acceptance was assessed among 40 first-grade children, who were shown four slides of two 7-year-old children (one boy, one girl) in two poses (one thumb sucking, one not). After viewing each slide in their classrooms, the children answered 10 numerically weighted questions related to peer acceptance. To limit the possibility that the children would determine the girl and boy were the same in each pose, the slide presentation was counterbalanced across two sessions 1 week apart. Using a repeated-measures analysis of variance, the authors compared composite scores on each question for both poses. The results indicate that while in the thumb-sucking pose, the children were rated as significantly less intelligent, happy, attractive, likeable, and fun and less desirable as a friend, playmate, seatmate, classmate, and neighbor than when they were in the non-thumb sucking pose. These findings suggest that the risk of reduced social acceptance should be added to the list of potentially harmful effects of chronic thumb sucking in school-age children. PMID- 8464668 TI - Issues involved in the definition and classification of chronic health conditions. AB - The need for a widely applicable definition of chronic conditions for research, policy, and program development has led to an extensive review of the development of such definitions, the considerations involved in their use, and some recommendations for a new approach. This paper examines some of the methodologic and conceptual issues related to defining and classifying chronic conditions and describes some consequences resulting from decisions made about these issues. While most examples are taken from child health applications, the basic concepts apply to all age groups. The dominant method for identifying and classifying children as having a chronic condition has relied on the presence of an individual health condition of lengthy duration. This condition-specific or "categorical" approach has increasingly seemed neither pragmatically nor conceptually sound. Thus, the development of a "generic" approach, which focuses on elements that are shared by many conditions, children, and families, is recommended. Such a definition might reflect the child's functional status or ongoing use of medical services over a specified time period. In addition, it is suggested that conditions be classified based on the experience of individual children, thus emphasizing the tremendous variability in expression of seemingly similar conditions. PMID- 8464669 TI - Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome. AB - This study evaluated possible acute effects of neutrophil elastase on neonatal pulmonary morbidity. The activity of free elastase and alpha 1-proteinase inhibitor as well as concentrations of elastase-alpha 1-proteinase inhibitor in tracheal aspirate fluid of neonates with severe respiratory distress syndrome (fraction of inspired oxygen > 0.6, mechanical ventilation) were analyzed between 6 and 36 hours after surfactant replacement therapy. One hundred forty neonates were included in this prospective study. Characteristics, disease severity, and ventilatory requirements were nearly identical in both groups. All patients were treated with natural porcine surfactant (Curosurf) at an age of 2 to 15 hours. In 42 neonates (30%) considerable activities of free elastase were detected (805 micrograms/L; 100 to 1850 [median, 25th to 75th percentile]); in 98 neonates (70%) who had protective levels of alpha 1-proteinase inhibitor, no elastase activity was detected. The average concentrations of elastase-alpha 1-proteinase inhibitor were significantly increased in patients with free elastase activity when compared with those of the nonelastase group. In logistic regression analyses, 28-day outcome data showed a pronounced increase in risk of pulmonary interstitial emphysema for patients with free elastase activity in tracheal aspirate fluid. The incidence of other pulmonary and nonpulmonary complications was very similar in both groups. It is concluded that elastolytic damage and barotrauma may both contribute to acute pulmonary injury in the early stages of respiratory distress syndrome. PMID- 8464670 TI - Hemoglobin S and C traits: contributing causes for decreased mean hematocrit in African-American children. AB - Several nutritional surveys have shown that African-American children have lower mean hematocrit and hemoglobin values than white children. While the high prevalence of both alpha and beta thalassemias in African-American children can partly account for the lower hematologic values, the remaining differences cannot be explained. African-American individuals have a high prevalence of traits for hemoglobin S (HbAS) and hemoglobin C (HbAC). The mean hematocrit of children with normal hemoglobin AA (HbAA) (n = 15637) was compared with that of children with traits for HbAS (n = 1197) and HbAC (n = 440). For both sexes, the mean hematocrit of subjects with HbAC and HbAS was 1.5 and 1 point lower, respectively, than that of subjects with HbAA. These differences were highly significant statistically. When the data were examined with regard to age and sex, statistically significant differences were present for all groups analyzed except the 11- through 14-year-old male group for HbAC and the 15- through 19 year-old male group for HbAS. Thus, the presence of Hb S and C traits is associated with a lower hematocrit. This reduced hematocrit may significantly contribute to the racial differences in mean hematocrit due to the high prevalence of these traits in African-American children. PMID- 8464671 TI - Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group. AB - This prospective, randomized, blinded clinical trial was conducted to test whether therapy with cromolyn sodium might decrease the incidence or severity of bronchopulmonary dysplasia when given to newborns with respiratory distress syndrome. Cromolyn (20 mg) or placebo was aerosolized to intubated newborns with respiratory distress syndrome every 6 hours, beginning on the first day of intubation. Patients were stratified by birth weight less than 1000 g and 1000 to 2000 g; primary outcome success was defined as survival to 30 days without oxygen dependence. Of 10 patients enrolled who were less than 1000 g birth weight, there were no treatment successes, preventing outcome analysis. The study was discontinued after 28 patients of 1000 to 2000 g birth weight had been studied, at which time it had been found with 95% confidence, with a power of .80, that cromolyn sodium did not decrease by 50% the incidence of bronchopulmonary dysplasia. Severity of bronchopulmonary dysplasia was also similar, with 4 patients in the treatment group and 3 in the placebo group receiving mechanical ventilation at 30 days. Possible reasons for this study outcome include (1) a delivered dose too small to produce a clinical effect; (2) the start of therapy too late to prevent the onset of inflammation; (3) inadequate effect of cromolyn on polymorphonuclear cells in vivo; or (4) development of bronchopulmonary dysplasia through factors unaffected by the actions of cromolyn. PMID- 8464672 TI - Contralateral renal abnormalities in patients with renal agenesis and noncystic renal dysplasia. AB - The prevalence of contralateral renal abnormalities in noncystic-dysplastic kidney (NCDK) disease and renal agenesis is unknown. Twenty-four patients with NCDK disease and 16 patients with renal agenesis were studied in this 11-year retrospective study. In all patients the urinary system was evaluated by renal ultrasonography, and excretory urography or radionuclide scan. In addition, voiding cystourethrography was performed in 21 of 24 patients with NCDK disease and in 10 of 16 patients with renal agenesis. In those patients where voiding cystourethrography was performed, 14 (67%) patients with NCDK disease and 9 (90%) patients with renal agenesis had contralateral urologic abnormalities. Contralateral vesicoureteral reflux was the most common contralateral abnormality identified in 9 (43%) patients with NCDK disease and in 3 (30%) patients with renal agenesis. It is concluded that contralateral urologic abnormalities are common in patients with NCDK disease and in patients with renal agenesis and that vesicoureteral reflux is the most common contralateral abnormality noted. PMID- 8464673 TI - Attention deficit hyperactivity disorder, creativity, and the effects of methylphenidate. AB - Given that children with attention deficit hyperactivity disorder (ADHD) are more impulsive than peers, this study explored whether they are correspondingly more creative, and whether creativity declines when impulsivity is decreased through methylphenidate (Ritalin) therapy. A repeated-measures quasi-experimental design was used to compare the performance of 19 boys with previously diagnosed ADHD and 21 comparison boys aged 8 through 11 on two administrations of alternate forms of the Torrance Tests of Creative Thinking-Figural (nonverbal). Boys with ADHD received prescribed methylphenidate only for the first session. Overall, mean Torrance summary scores for comparison boys (mean = 115.1, SD = 16.1) were higher than for boys with ADHD (mean = 107.6, SD = 12.7). However, the difference between means was small (7%) and did not meet the 25% criterion for a clinically significant difference. No changes in performance over time (comparison group) or medication state (ADHD group) were observed. These data suggest that, when measured nonverbally, the creative thinking performance of boys with ADHD is not superior to that of peers who do not have ADHD. Regarding the effects of methylphenidate, prescribed therapy did not influence performance on this measure of creative thinking. PMID- 8464674 TI - Appearance of the hymen at birth and one year of age: a longitudinal study. AB - The increase in the number of prepubertal girls who require evaluation of possible sexual abuse creates a need for detailed information, not previously available from cross-sectional studies, on the influence of aging on the hymen's appearance. This study was undertaken to evaluate and document, using a longitudinal design, changes in the hymen's morphology in 62 girls without a history of sexual abuse between birth and their first birthday. Labial agglutination extensive enough to obscure the inferior half of the hymen was observed in 5 girls (8%) at 1 year of age. Thirty-three (58%) of the remaining 57 infants experienced a marked decrease in the amount of their hymenal tissue between birth and 1 year. Significantly more infants at 1 year of age had a crescentic configuration (0% vs 28%), and significantly fewer had an external ridge (82% vs 14%) as compared to the newborn period. An annular hymen with a central or ventrally displaced opening progressed to a crescentic hymen in 13 children by 1 year, 77% (10/13) of whom were observed to have a notch (cleft) at the 12 o'clock position on the earlier study. A superior notch appeared for the first time in 9 girls. Lateral notches resolved in 5 cases and persisted in 2. Inferior notches between the 4 and 8 o'clock positions were not observed at birth or 1 year. Hymenal tags resolved in 2 instances, persisted in the same location in 2, and appeared for the first time in 4 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464675 TI - Bulimic behaviors among interscholastic wrestlers: a statewide survey. AB - Wrestlers are known for their extreme weight-cutting practices including fasting, food and fluid restriction, and dehydration. Using a stratified statewide survey, this investigation elucidated weight loss practices, nutritional knowledge, and bulimic behaviors among 713 high school wrestlers in Wisconsin. Results showed that 1.7% of the wrestlers answered questions consistent with all five criteria for bulimia nervosa, a rate higher than expected for adolescent males. An additional 43% exhibited weight-cutting practices similar to those of the wrestlers who met all bulimia nervosa criteria. The average wrestler lost 3.2 kg to compete, cycled 1.8 kg weekly, and fasted 20 hours prior to weigh-in. More extreme behaviors occurred among the 45% who met two or more bulimia nervosa criteria on their questionnaire; 19% frequently fasted, 25% restricted fluids, 34% used rubber suits, and 8% vomited. These results are comparable with data published over the past 20 years. Efforts to curtail these behaviors through regulations restricting weight loss coupled with sound nutritional information are warranted. Physicians and health professionals should be alert to potential eating disorders within this population. PMID- 8464676 TI - The physician-doctor relationship. PMID- 8464678 TI - Hair-grooming syncope seizures. PMID- 8464677 TI - Systemic reactions to measles-mumps-rubella vaccine skin testing. PMID- 8464679 TI - Perianal findings in infants 18 months of age or younger. PMID- 8464680 TI - Acellular pertussis vaccine booster. PMID- 8464681 TI - American Academy of Pediatrics Committee on School Health. Prevention of hepatitis B virus infection in school settings. PMID- 8464682 TI - Sale of individual cigarettes: a new development. PMID- 8464683 TI - It's not Henoch-Schonlein purpura (HSP) PMID- 8464684 TI - Sudden infant death syndrome and sleeping position. PMID- 8464685 TI - Guidelines vs the legal standard of care and screening for polycythemia. PMID- 8464686 TI - Screening for treatable disorders. PMID- 8464687 TI - Neonatal genital prolapse. PMID- 8464688 TI - Lead screening. PMID- 8464689 TI - Lead and IQ. PMID- 8464690 TI - The lead debate. PMID- 8464691 TI - Immunization of preterm infants. PMID- 8464692 TI - Noncomplementary DNA double-strand-break rejoining in bacterial and human cells. AB - We examined the rejoining of noncomplementary restriction enzyme-produced DNA double-strand breaks in Escherichia coli and in cultured human cells. The enzymes used in this study, ClaI, BamHI and SalI, produce double-strand breaks with 5 protruding single strands. The joining of a ClaI-produced DNA end to a BamHI produced end or to a SalI-produced end was examined at the DNA sequence level. End rejoining in E.coli was studied by transforming cultures with linear plasmid DNA that was gel purified from restriction digests, and end rejoining in cultured human cells was studied by introducing enzymes into the cells by electroporation. The human cells used contain an Epstein-Barr virus (EBV)-based shuttle vector, pHAZE, that was recovered and introduced into E.coli for further analysis. The major products of DNA end-joining processes observed in linear plasmid transformed E.coli and in the human cells exposed to restriction enzymes were identical. Furthermore, the deletions observed in both systems and in the spontaneous mutant plasmids in untreated human cells had a common underlying feature: short stretches of directly repeated DNA at the junction sites. PMID- 8464693 TI - Sequence and organization of large subunit rRNA genes from the extrachromosomal 35 kb circular DNA of the malaria parasite Plasmodium falciparum. AB - The malaria parasite Plasmodium falciparum carries an extrachromosomal 35 kb circular DNA molecule of unknown provenance. A striking feature of the circle is a palindromic sequence of genes for subunit rRNAs and several tRNAs, spanning ca. 10.5 kb. The palindrome has an intriguing resemblance to the inverted repeat of plastid genomes, and the sequence and putative secondary structure of the malarial large subunit (LSU) rRNA described in this report were used as the basis of a phylogenetic study. The malarial rRNA was found to be highly divergent in comparison with a selected group of chloroplast LSU rRNAs but was more closely related to them than to mitochondrial LSU rRNA genes. PMID- 8464694 TI - Unique secondary and tertiary structural features of the eucaryotic selenocysteine tRNA(Sec). AB - Cotranslational insertion of selenocysteine into selenoenzymes is mediated by a specialized transfer RNA, the tRNA(Sec). We have carried out the determination of the solution structure of the eucaryotic tRNA(Sec). Based on the enzymatic and chemical probing approach, we show that the secondary structure bears a few unprecedented features like a 9 bp aminoacid-, a 4 bp thymine- and a 6 bp dihydrouridine-stems. Surprisingly, the eighth nucleotide, although being a uridine, is base-paired and cannot therefore correspond to the single-stranded invariant U8 found in all tRNAs. Rather, experimental evidence led us to propose that the role of the invariant U8 is actually played by the tenth nucleotide which is an A, numbered A8 to indicate this fact. The experimental data therefore demonstrate that the cloverleaf structure we derived experimentally resembles the hand-folded model proposed by Bock et al (ref. 3). Using the solution data and computer modelling, we derived a three-dimensional structure model which shows some unique aspects. Basically, A8, A14, U21 form a novel type of tertiary interaction in which A8 interacts with the Hoogsteen sites of A14 which itself forms a Watson-Crick pair with U21. No coherent model containing the canonical 15 48 interaction could be derived. Thus, the number of tertiary interactions appear to be limited, leading to an uncoupling of the variable stem from the rest of the molecule. PMID- 8464695 TI - Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development. AB - To begin to examine the function of genes that control early development in the hindbrain, we have screened an embryonic zebrafish cDNA library with a murine krox-20 gene probe that contained the conserved zinc finger regions. We have isolated two overlapping cDNAs, zf187 and zf201 which are homologues of the murine krox-20 gene. The N-terminal of the longest cDNA (zf201) contains two acidic regions identical to those of the murine krox-20. This indicates that the functional organisation of these proteins is probably conserved. Northern Blot analysis identified a single transcript of 2.0 kb. Wholemount in situ hybridisation established that expression of the zebrafish gene (krx-20) first appears at 100% epiboly as a single anterior domain of the prospective neuroepithelium, followed very soon after by a second more posterior domain. The alternating pattern of expression of this gene in rhombomeres(r) r3 and r5 is apparent by 12 hr post-fertilisation, that is prior to the morphological appearance of the rhombomeres. Around 14 hr neural crest migration begins from the dorsal surface of r5, moving caudally into r6 and then ventrally towards the pharyngeal arches. Crest migration is not apparent at or after 16 hr. No neural crest migration was observed from r3. Expression of krx-20 is down regulated firstly in r3 around 26 hr and later in r5 around 30 hr. PMID- 8464696 TI - The abundance of various polymorphic microsatellite motifs differs between plants and vertebrates. AB - The abundance of different simple sequence motifs in plants was accessed through data base searches of DNA sequences and quantitative hybridization with synthetic dinucleotide repeats. Database searches indicated that microsatellites are five times less abundant in the genomes of plants than in mammals. The most common plant repeat motif was AA/TT followed by AT/TA and CT/GA. This group comprised about 75% of all microsatellites with a length of more than 6 repeats. The GT/CA motif being the most abundant dinucleotide repeat in mammals was found to be considerably less frequent in plants. To address the question if plant simple repeat sequences are variable as in mammals, (GT)n and (CT)n microsatellites were isolated from B.napus. Five loci were investigated by PCR-analysis and amplified products were obtained for all microsatellites from B. oleracea, B.napus and B.rapa DNA, but only for one primer pair from B.nigra. Polymorphism was detected for all microsatellites. PMID- 8464697 TI - Atomic force microscopy of DNA and bacteriophage in air, water and propanol: the role of adhesion forces. AB - We have developed a chemical treatment for the mica surface which allows biopolymers to be held in place for atomic force microscopy, even under water, using conventional, untreated force sensing tips. We illustrate the procedure with images of lambda DNA and fd phage. The phage adheres well enough to permit in situ imaging of the adsorption process in water. These experiments yield a mean length for the phage of 883 +/- 72 nm. This compares with a measured length of 883 +/- 33 nm when the phage are imaged after drying following adsorption from water, showing that the effect of dehydration is quite small. Adhesion forces between the force sensing tip and the substrate and the sensing tip and the biomolecules are very different in the three media (air, water and propanol). The apparent height of the phage and the width and height of the DNA depends upon these adhesion forces quite strongly. In contrast, changing the Hookean spring force exerted by the scanning tip makes little difference. These results suggest that the chemical factors involved in adhesion can dominate atomic force images and that the composition of the scanning tip is at least as important a factor as its geometry. PMID- 8464698 TI - Multifunctional repressor KorB can block transcription by preventing isomerization of RNA polymerase-promoter complexes. AB - The KorB protein of broad-host-range plasmid RK2 is a transcriptional repressor involved in the control of genes for plasmid replication, conjugative transfer and stable maintenance. We have purified this protein close to homogeneity from cells harbouring an overexpression vector with the korB gene under the control of the tac promoter. KorB binds to restriction fragments bearing its proposed operator sequence, OB. Its interaction with this palindromic site was confirmed by DNaseI or hydroxyl radical footprinting at two OB sequences from RK2. Comparisons showed that the OB context affects the nature of the footprint. Our evidence suggests that KorB is a tetramer. As such, it may be able to bind two sites simultaneously on the same or on different DNA molecules. Using the korABF promoter, which is subject to KorB repression, we demonstrate by footprinting and restriction protection that KorB and RNA polymerase can bind simultaneously. Permanganate footprinting showed that KorB represses this promoter by preventing isomerization of the RNA polymerase-promoter complex from the closed to open form. PMID- 8464699 TI - Correlation between observed transcripts and sequenced ORFs of chromosome III of Saccharomyces cerevisiae. AB - Most of the 155 transcripts of the genes on chromosome III of S.cerevisiae that were identified by a series of Northern hybridization experiments (Yoshikawa, A. and Isono, K., Yeast 6, 383-401, 1990) have been correlated with the open reading frames (ORFs) deduced from the nucleotide sequence data for this chromosome (Oliver, S.G. et al., Nature 357, 38-46, 1992). This was performed by comparing the experimentally constructed physical map and the one produced from the nucleotide sequence data, and then the sizes and positions of observed transcripts and those of sequenced ORFs. The data thus provide information for possible products of the sequenced ORFs (genes) of chromosome III of S.cerevisiae as well as their likely levels of expression in vegetatively growing cells. PMID- 8464700 TI - The production of PCR products with 5' single-stranded tails using primers that incorporate novel phosphoramidite intermediates. AB - We have prepared several novel phosphoramidites and have synthesised oligonucleotides incorporating them internally. The presence of these residues in an oligonucleotide template presents an impossible barrier to primed synthesis by Taq DNA polymerase. When extended as polymerase chain reaction products, these oligonucleotides no longer serve as templates for the polymerase beyond the insertion sites of the modified intermediates, thereby producing single-stranded tails on amplification products. These tails can then be used for solid phase capture and colorimetric detection of PCR products. PMID- 8464701 TI - Secondary structure of the HIV-2 leader RNA comprising the tRNA-primer binding site. AB - The initiation of reverse transcription of a retroviral RNA genome occurs by a tRNA primer bound near the 5' end of the genomic RNA at a position called the primer-binding site (PBS). To understand the molecular basis for this RNA-RNA interaction, the secondary structure of the leader RNA of the human immunodeficiency virus type 2 (HIV-2) RNA was analyzed. In vitro synthesized HIV 2 RNA was probed with various structure-specific enzymes and chemicals. A computer program was then used to predict the secondary structure consistent with these data. In addition, the nucleotide sequences of different HIV-2 isolates were used to screen for the occurrence of covariation among putative base pairs. The primary sequences have diverged rapidly in some HIV-2 isolates, however, some strikingly conserved secondary structure elements were identified. Most nucleotides in the leader region are involved in base pairing. An exception is the PBS sequence, of which 15 out of 18 nucleotides are exposed in an internal loop. These findings suggest that the overall structure of the HIV-2 genome has evolved to facilitate an optimal interaction with its tRNA primer. PMID- 8464702 TI - Downregulation of HLA class I expression by c-myc in human melanoma is independent of enhancer A. AB - High constitutive expression of the c-myc oncogene in human melanoma leads to downregulation of expression of HLA Class I genes. The genes at the HLA-B locus are preferentially affected. To investigate the mechanism of downregulation, the activity of the main HLA Class I enhancer, enhancer A-region I, was compared in a panel of c-myc transfectants with increasing myc expression. Gel retardation experiments demonstrated in all tested cell lines binding of the transcription factors KBF1 and NF-kappa B to the enhancer. However, no correlation between the levels of HLA Class I expression and binding to the enhancer could be established. Strikingly, the cell line with the highest c-myc expression showed more binding of KBF1 and NF-kappa B than the parental cell line. By using CAT reporter plasmids in transient transfection assays we investigated the in vivo function of enhancer A-region I in the c-myc transfectant panel. Again, c-myc expression had no effect at all on the activity of enhancer A. This study shows that HLA Class I expression is regulated by the c-myc oncogene at the level of transcription, but that the main HLA Class I enhancer is not involved in this process. PMID- 8464703 TI - Differential splicing in mouse thymus generates two forms of terminal deoxynucleotidyl transferase. AB - A new form of TdT mRNA has been identified by screening a mouse thymus cDNA library. It contains an open reading frame of 1527 base pairs corresponding to a protein containing 509 aminoacids, whereas the previously identified mouse TdT mRNA is composed of 1587 base pairs and encodes a protein of 529 aminoacids. Analysis of a mouse genomic clone containing the 3' portion of the TdT gene shows that these twenty additional aminoacids are encoded by an additional exon located between exons X and XI. Both forms of TdT mRNA are present in the thymus and could be generated by alternative splicing. The cDNA reported here corresponds to the major form of TdT mRNA in Balb/c mice and closely resembles human and bovine TdT cDNA. Expression of this cDNA in mammalian cells shows that it encodes a functional protein capable of catalysing N region insertions at the recombination junction of an episomic recombination substrate. PMID- 8464704 TI - The pre-mRNA binding K protein contains a novel evolutionarily conserved motif. AB - The K protein is among the major pre-mRNA-binding proteins (hnRNPs) in vertebrate cell nuclei. It binds tenaciously to cytidine-rich sequences and is the major oligo(rC/dC)-binding protein in vertebrate cells. We have cloned a cDNA of the Xenopus laevis hnRNP K and determined its sequence. The X.laevis hnRNP K is a 47 kD protein that is remarkably similar to its human 66 kD counterpart except for two large internal deletions. The sequence of hnRNP K contains a 45 amino acid repeated motif which is almost completely conserved between the X.laevis and human proteins. We found that this repeated motif, the KH motif (for K homology), shows significant homology to several proteins some of which are known nucleic acids binding proteins. The homology is particularly strong with the archeabacterial ribosomal protein S3 and with the saccharomyces cerevisiae protein MER1 which is required for meiosis-specific splicing of the MER 2 transcript. As several of the proteins that contain the KH motif are known to bind RNA, this domain may be involved in RNA binding. PMID- 8464705 TI - HNF-4 increases activity of the rat Apo A1 gene. AB - Apolipoprotein A1 (Apo A1) is the major protein component of high density lipoprotein (HDL) particles. HDL particles mediate the removal of cholesterol from extra-hepatic tissues via a process known as reverse cholesterol transport. Augmented production of Apo A1 will likely be beneficial to those who suffer from the consequences of hypercholesterolemia. One approach to increase expression of the protein is to identify nuclear factor(s) that enhance Apo A1 promoter activity. Therefore, we have used transient transfection to study a limited portion (-474 to -7) of the gene and showed that a cis-regulatory element, site C had a permissive effect on the ability of an adjacent site B to increase promoter activity by 30-fold. The importance of element C prompted us to identify the factor(s) that interact with this site. Results showed that HNF-4, a new member of the thyroid/steroid hormone receptor superfamily interacts with site C to enhance activity of the promoter. Based on this observation and that of the known inhibitory effects of ARP-1 on site C, we postulate a model which may account for the tissue-specific expression of the rat Apo A1 gene. PMID- 8464706 TI - Large scale, liquid phase synthesis of oligonucleotides by the phosphoramidite approach. AB - A new method for the liquid phase synthesis of oligonucleotides is described which makes use of polyethylene glycol (PEG) as soluble support and phosphoramidite derivatives as synthons. The new synthetic protocol was applied to a quite large scale production (about 100 mumoles) of such compounds up to the 20mer level. This solution method, called HELP High Efficiency Liquid Phase) Plus, appears effective in terms of speed and coupling yield and can be evaluated for the production of large amount of oligonucleotides. PMID- 8464707 TI - Splicing choice from ten variant exons establishes CD44 variability. AB - The enormous heterogeneity of the surface protein designated CD44 is in part due to posttranslational modification, and in part due to differential splicing. Alternative splicing occurs within one particular region encoding the extracellular portion of the protein. Comparison of various cDNA clones with different 'inserts' in this variable region with sequences of genomic clones from the mouse has revealed the existence of at least ten exons from which sequences are chosen by alternative splicing. Various combinations of these exons account for the tremendous heterogeneity of CD44 molecules expressed in different tissues, and in progressing tumor cells. The existence of different isoforms of CD44 suggests a broad spectrum of yet unknown physiologic functions. PMID- 8464708 TI - Exoquence DNA sequencing. AB - We have developed a strategy for DNA sequencing based on exonuclease III digestion followed by double strand specific endonuclease digestion and direct dideoxynucleotide sequencing reaction. This strategy eliminates the need for subcloning, oligonucleotide primers, and prior knowledge of the DNA to be sequenced. All template and primer duplexes needed for sequencing a complete insert can be prepared in one day from uncharacterized starting DNA. Sequence information can be obtained from different regions of the DNA simultaneously. The method uses double-stranded DNA to generate single-stranded template and primer, and thus produces high quality sequence results. Commercially available dideoxy sequencing kits are well suited for this method. The strategy should be applicable for both automatic and routine laboratory DNA sequencing. PMID- 8464709 TI - Hydrogen peroxide-induced c-fos expression is mediated by arachidonic acid release: role of protein kinase C. AB - We found previously that stimulation of c-fos and c-myc mRNA expression are early events in hydrogen peroxide-induced growth in rat aortic smooth muscle (RASM) cells. In the present study, we investigated the role of phospholipase A2 (PLA2) and protein kinase C (PKC) in mediating hydrogen peroxide-induced c-fos mRNA expression in RASM cells. Mepacrine and p-bromophenacylbromide, potent inhibitors of PLA2 activity, blocked hydrogen peroxide-induced c-fos mRNA expression. Arachidonic acid, a product of PLA2 activity, stimulated the expression of c-fos mRNA with a time course similar to that of hydrogen peroxide. PKC down-regulation attenuated both hydrogen peroxide and arachidonic acid-induced c-fos mRNA expression by 50%. Nordihydroguaiaretic acid (a lipoxygenase-cytochrome P450 monooxygenase inhibitor) significantly inhibited both hydrogen peroxide and arachidonic acid-induced c-fos mRNA expression, whereas indomethacin (a cyclooxygenase inhibitor) had no effect. Together, these findings indicate that 1) hydrogen peroxide-induced c-fos mRNA expression is mediated by PLA2-dependent arachidonic acid release, 2) both PKC-dependent and independent mechanisms are involved in hydrogen peroxide-induced expression of c-fos mRNA and 3) arachidonic acid metabolism via the lipoxygenase-cytochrome P450 monooxygenase pathway appears to be required for hydrogen peroxide-induced expression of c-fos mRNA. PMID- 8464710 TI - Comparative analysis of the locus control region of the rabbit beta-like gene cluster: HS3 increases transient expression of an embryonic epsilon-globin gene. AB - The rabbit homolog to the locus control region (LCR) of the human beta-like globin gene cluster was isolated, and long segments containing the DNase I hypersensitive sites (HS) were sequenced. The order and spacing of HS4, HS3, HS2 and HS1 are conserved between rabbit and human. Alignment of these sequences with their homologs from human, goat, and mouse shows that very long segments of DNA match between species, for over a thousand base pairs on either side of the previously identified functional cores, indicating that some important functions are found outside the cores. The activity of rabbit HS2 and HS3 was tested by attaching each to a novel reporter gene constructed by inserting the luciferase coding region into the rabbit epsilon-globin gene. In contrast to previous reports showing no effect of human or mouse HS3 on transient expression, both the rabbit HS2 and HS3 DNA fragments separately increased transient expression from the epsilon-luciferase hybrid gene and expression from stably integrated constructs in K562 erythroleukemia cells. PMID- 8464711 TI - Identification and characterization of new human medium reiteration frequency repeats. AB - We report nine new families of human medium reiteration frequency interspersed repetitive elements (MER elements). They were identified by computer-assisted analyses. Six of them were independently confirmed as repetitive families by DNA DNA hybridization, and the number of elements for each of these families was estimated by plaque hybridization assay. The involvement of some of the reported MER elements in genetic rearrangements is demonstrated. PMID- 8464712 TI - DNA-substrate sequence specificity of human G:T mismatch repair activity. AB - G:T mispairs in DNA originate spontaneously via deamination of 5-methylcytosine. Such mispairs are restored to normal G:C pairs by both E. coli K strains and human cells. In this study we have analyzed the repair by human cell extracts of G:T mismatches in various DNA contexts. We performed two sets of experiments. In the first, repair was sequence specific in that G:T mispairs at CpG sites at four different CpG sites were repaired, but a G:T mismatch at a GpG site was not. Cytosine hemimethylation did not block repair of a substrate containing a CpG/GpT mismatch. In the second set of experiments, substrates with a G:T mismatch at a fixed position were constructed with an A, T, G, or C 5' to the mismatched G, and alterations in the complementary strand to allow otherwise perfect Watson-Crick pairing. All were incised just 5' to the mismatched T and competed for repair incision with a G:T substrate in which a C was 5' to the mismatched G. Thus human G:T mismatch activity shows sequence specificity, incising G:T mismatched pairs at some DNA sites, but not at others. At an incisable site, however, incision is little influenced by the base 5' to the mismatched G. PMID- 8464714 TI - Nucleotide sequence of the small ribosomal RNA of Encephalitozoon cuniculi. PMID- 8464715 TI - Nucleotide sequence of the 3' half of zucchini yellow mosaic virus (Singapore isolate) genome encoding the 4K protein, protease, polymerase and coat protein. PMID- 8464713 TI - c-Jun is phosphorylated by the DNA-dependent protein kinase in vitro; definition of the minimal kinase recognition motif. AB - The DNA-dependent protein kinase (DNA-PK) phosphorylates a number of transcription factors. Here, we show that the DNA-PK modifies c-Jun in vitro and that serine residue 249 (Ser-249) is required for phosphorylation to occur. This residue corresponds to one of three sites of c-Jun that are phosphorylated in vivo and which negatively regulate c-Jun DNA binding in vitro. However, we find that phosphorylation of c-Jun by the DNA-PK does not interfere with DNA binding, indicating that phosphorylation at other sites is required for this effect. Mutagenesis of the phosphorylated region of c-Jun reveals that the primary amino acid sequence recognised by the DNA-PK consists of the sequence Ser-Gln, and that adjacent acidic residues potentiate kinase activity. Furthermore, when this site is placed within the context of a second protein, it confers DNA-PK directed phosphorylation upon that protein. Our findings will facilitate identification of DNA-PK phosphorylation sites in other transcription factors. PMID- 8464716 TI - Cloning of a Drosophila cDNA with sequence similarity to human transcription factor RAP74. PMID- 8464717 TI - Determination of the DNA sequence of the 5.8S ribosomal gene of Heterobasidion annosum and Heterobasidion araucariae. PMID- 8464718 TI - PCR amplification of megabase DNA with tagged random primers (T-PCR). PMID- 8464719 TI - Cloning biologically active geminivirus DNA using PCR and overlapping primers. PMID- 8464720 TI - Microtechnique for electron microscopy of DNA. PMID- 8464721 TI - A putative homology of U2AF65 in S. cerevisiae. PMID- 8464722 TI - Lack of peptide-release activity responding to codon UGA in Mycoplasma capricolum. AB - In Mycoplasma capricolum, a relative of Gram-positive eubacteria with a high genomic AT-content (75%), codon UGA is assigned to tryptophan instead of termination signal. Thus, in this bacterium the release factor 2 (RF-2), that recognizes UAA and UGA termination codons in eubacteria such as Escherichia coli and Bacillus subtilis, would be either specific to UAA or deleted. To test this, we have constructed a cell-free translation system using synthetic mRNA including codon UAA [mRNA(UAA)], UAG [mRNA(UAG)] and UGA [mRNA(UGA)] in-frame. In the absence of tryptophan, the translation of mRNA(UGA) ceased at UGA sites without appreciable release of the synthesized peptides from the ribosomes, whereas with mRNA(UAA) or mRNA(UAG) the bulk of the peptides was released. Upon addition of the E.coli S-100 fraction or B.subtilis S-100 fraction to the translation system, the synthesized peptides with mRNA(UGA) were almost completely released from the ribosomes, presumably because of the presence of RF-2 active to UGA in the added S-100 fraction. These data suggest that RF-2 is deleted or its activity to UGA is strongly weakened in M.capricolum. PMID- 8464723 TI - Visualising the kinetics of dissociation of actinomycin from individual sites in mixed sequence DNA by DNase I footprinting. AB - We have investigated the kinetics of dissociation of actinomycin D from DNA by a variation of the footprinting technique. Complexes of actinomycin with a radiolabelled DNA fragment (tyrT) were dissociated by addition of a large excess of unlabelled calf thymus DNA and the mixture subjected to DNase I footprinting at subsequent intervals. The rates at which the footprints disappeared varied between the different binding sites. The dissociation was temperature dependent with average time constants of 30 s, 10 mins and 2 hours at temperatures of 37 degrees C, 20 degrees C and 4 degrees C respectively. The dissociation from a DNA fragment containing the synthetic insert T9GCA9 was significantly faster, with a half-life of about 1 min at 20 degrees C. In contrast, the dissociation of distamycin was too fast to measure (< 5 s) even at 4 degrees C. PMID- 8464724 TI - Evolutionary conservation of excision repair in Schizosaccharomyces pombe: evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene. AB - Cells mutated at the rad13 locus in the fission yeast, Schizosaccharomyces pombe are deficient in excision-repair of UV damage. We have cloned the S.pombe rad13 gene by its ability to complement the UV sensitivity of a rad13 mutant. The gene is not essential for cell proliferation. Sequence analysis of the cloned gene revealed an open reading-frame of 1113 amino acids with structural homology to the RAD2 gene of the distantly related Saccharomyces cerevisiae. The sequence similarity is confined to three domains, two close to the N-terminus of the encoded protein, the third being close to the C-terminus. The central region of about 500 amino acids shows little similarity between the two organisms. The first and third domains are also found in a related yet distinct pair of homologous S.pombe/S.cerevisiae DNA repair genes (rad2/YKL510), which have only a very short region between these two conserved domains. Using the polymerase chain reaction with degenerate primers, we have isolated fragments from a gene homologous to rad13/RAD2 from Aspergillus nidulans. These findings define new functional domains involved in excision-repair, as well as identifying a conserved family of genes related to RAD2. PMID- 8464725 TI - Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation. AB - Methylation at CpG dinucleotides to produce 5 methyl cytosine (5me-C) has been proposed to regulate the transcriptional expression of human Alu repeats. Similarly, methylation has been proposed to indirectly favor the transpositional activity of young Alu repeats by transcriptionally inactivating older Alu's through the very rapid transition of 5me-C to T. Both hypotheses are examined here by RNA polymerase III (Pol III) in vitro transcription of Alu templates using HeLa cell extracts. A limiting factor represses the template activity of methylated Alu repeats. Competition by methylated prokaryotic vector DNA's relieves repression, showing that the factor is not sequence specific. This competitor has no effect on the activity of unmethylated templates showing that the repressor is highly specific toward methylated DNA. While methylation of a single pair of CpG dinucleotides in the A box of the Poll III promoter is sufficient to cause repression, methylation elsewhere within the template also causes repression. The repressor causing these effects on the Pol III directed transcription of Alu repeats is thought to be a previously reported, repressor for Pol II directed templates. Young Alu repeats are transcriptionally more active templates than a representative older Alu subfamily member. Also, younger Alu's form stable transcriptional complexes faster, potentially giving them an additional advantage. The mutation of three CpG's to CpA's within and near the A box drastically decreases both the template activity and rate of stable complex formation by a young Alu member. The sensitivity of Alu template activity to CpG transitions within the A box partially explains the selective transpositional advantage enjoyed by young Alu members. PMID- 8464726 TI - Role of the 5' leader sequence of alfalfa mosaic virus RNA 3 in replication and translation of the viral RNA. AB - RNA 3 of alfalfa mosaic virus (AIMV) encodes the movement protein P3 and the viral coat protein which is translated from the subgenomic RNA 4. The 5'-leader sequences of RNA 3 of AIMV strains S, A, and Y differ in length from 314 to 392 nucleotides and contain a variable number of internal control regions of type 2 (ICR2 motifs) each located in a 27 nt repeat. Infectious cDNA clones were used to exchange the leader sequences of the three strains. This revealed that the leader sequence controls the specific ratio in which RNAs 3 and 4 are synthesized for each strain. In addition, it specifies strain specific differences in the kinetics of P3 accumulation in plants. Subsequent deletion analysis revealed that a 5'-sequence of 112 nt containing one ICR2 motif was sufficient for a 10 to 20% level of RNA 3 accumulation in protoplasts and a delayed accumulation in plants. An additional leader sequence of maximally 114 nt, containing two ICR2 motifs, was required to permit wildtype levels of RNA 3 accumulation. The effect of deletions in the leader sequence on P3 synthesis in vitro and in vivo was investigated. PMID- 8464727 TI - A study into the effects of protein binding on nucleotide conformation. AB - In this study, we examine the effects of binding to protein upon nucleotide conformation, by the comparison of X-ray crystal structures of free and protein bound nucleotides. A dataset of structurally non-homologous protein-nucleotide complexes was derived from the Brookhaven Protein Data Bank by a novel protocol of dual sequential and structural alignments, and a dataset of native nucleotide structures was obtained from the Cambridge Structural Database. The nucleotide torsion angles and sugar puckers, which describe nucleotide conformation, were analysed in both datasets and compared. Differences between them are described and discussed. Overall, the nucleotides were found to bind in low energy conformations, not significantly different from their 'free' conformations except that they adopted an extended conformation in preference to the 'closed' structure predominantly observed by free nucleotide. The archetypal conformation of a protein-bound nucleotide is derived from these observations. PMID- 8464728 TI - In vitro selection of fast-hybridizing and effective antisense RNAs directed against the human immunodeficiency virus type 1. AB - The rate of double strand formation between procaryotic antisense RNA and complementary RNA in vitro is known to correlate with the effectiveness of antisense RNA in vivo. In this work, an in vitro assay for determining the hybridization rates of a large number of antisense RNA species was developed. A set of HIV-1-directed antisense RNAs with the same 5'-end but successively shortened 3'-ends was produced by alkaline hydrolysis of a 150 nt HIV-1-directed antisense transcript. This mixture was used to determine hybridization rates for individual chain lengths with a complementary HIV-1-derived RNA in vitro. The second order binding rate constants of individual antisense RNA species differed by more than a factor of 100, although in some cases, slow-hybridizing and fast hybridizing antisense RNAs differed by only two or three 3'-terminally-located nucleotides. The results indicated that there was not a trivial dependence of binding rates on the chain length of antisense RNAs. Further, the binding rate constants determined in vitro for individual antisense RNA species correlated with the extent of inhibition of HIV-1 replication in vivo. PMID- 8464729 TI - The secondary structure of the 5'-noncoding region of beet necrotic yellow vein virus RNA 3: evidence for a role in viral RNA replication. AB - Secondary structure-sensitive chemical and enzymatic probes have been used to produce a model for the folding of the first 312 residues of the long 5' noncoding region of beet necrotic yellow vein virus RNA 3. The structure consists of two major domains, one of which includes long distance base-pairing interactions between two short sequence elements (Box I and Box II) situated between positions 237 and 292 and complementary elements (Box I' and II') near the 5'-terminus. Previous studies have shown that base pairing between these sequence elements (in either the plus-strand or minus-strand RNA) is important for RNA 3 accumulation during infection. RNA 3 transcripts were produced containing mutations which preferentially disrupted Box II-II' base pairing in either the plus- or minus-strand. In infection experiments, transcripts with mutations which disrupted the Box II-II' interaction in the plus-strand structure replicated less efficiently than mutants in which the Box II-II' interaction was disrupted in the minus-strand. These findings indicate that the complex 5' proximal plus-strand structure to which the Box II-II' interaction contributes comprises at least part of the promoter for plus-strand RNA synthesis. PMID- 8464730 TI - Use of a transactive regulatory mutant of Dictyostelium discoideum in a eucaryotic expression system. AB - The discoidin proteins of Dictyostelium discoideum are highly expressed during development. The Disc I gamma promoter allows the regulation of heterologous protein expression by experimental conditions. We report conditions under which the promoter activity is efficiently repressed during growth in the wildtype strain AX2. In addition we show that a mutant which overexpresses the discoidins also overexpresses the reporter genes beta-galactosidase, luciferase and CAT 10- to 100-fold when these are placed under the control of a Disc I gamma promoter. This system may be generally useful for the overexpression of genes in Dictyostelium, both for functional studies in vivo and for the production of heterologous proteins for purification. PMID- 8464731 TI - Template controlled coupling and recombination of oligonucleotide blocks containing thiophosphoryl groups. AB - Oxidation of a pair of 3'- and 5'-thiophosphoryloligonucleotides in the presence of a complementary oligonucleotide template is shown to provide an effective means for selectively linking oligonucleotide blocks. Coupling proceeds rapidly and efficiently under mild conditions in dilute aqueous solutions (microM range for oligomers, 2-15 min at 0-4 degrees C with K3Fe(CN)6 or KI3 as oxidant). This chemistry was demonstrated by polymerization of a thymidylate decamer derivative (sTTTTTTTTTTs) in the presence of poly(dA) and by coupling oligomers possessing terminal thiophosphoryl groups (ACACCCAATTs + sCTGAAAATGG and ACACCCAATs + sCTGAAAATGG) in the presence of a template (CCATTTTCAGAATTGGGTGT). Efficient linking of 5' to 3' phosphoryl groups can be achieved under conditions where virtually no coupling takes place in absence of a template. A novel feature of the chemistry is that catalyzed recombinations of oligomers containing internal OP(O)(O-)SSP(O)(O-)O- linkages can be directed by hydrogen bonding to a complementary oligonucleotide. Convenient procedures are reported for solid phase synthesis of the requisite oligonucleotide 3'- and 5'-phosphorothioates. PMID- 8464732 TI - Duplicated KOX zinc finger gene clusters flank the centromere of human chromosome 10: evidence for a pericentric inversion during primate evolution. AB - Two related zinc finger (ZNF) gene clusters from the pericentromeric region of human chromosome 10, defined by cDNAs of the KOX series, have been cloned in yeast artificial chromosomes (YACs). The two clusters evolved by duplication of an ancestral gene cluster before the divergence of the human and great ape lineages. Included in cluster A are the ZNF gene sequences ZNF11A, ZNF33A, and ZNF37A, while cluster B comprises the related sequences ZNF11B, ZNF33B and ZNF37B. Genes from both clusters are expressed: cDNAs KOX2, KOX31 and KOX21 derive from ZNF11B, ZNF33A and ZNF37A, respectively. Further YACs have been isolated which link ZNF11A and ZNF33A to another gene, ZNF25, defined by cDNA clone KOX19. Therefore ZNF25 also forms part of cluster A, but has no counterpart in cluster B. Surprisingly, the KOX ZNF gene clusters are located on opposite sides of the centromere: cluster A maps to 10p11.2, while cluster B is in 10q11.2. This suggests the occurrence during primate evolution of a previously undescribed pericentric inversion subsequent to the cluster duplication. The evolution of this subset of KOX ZNF genes has therefore involved three types of genetic event: local gene duplication, gene cluster duplication, and chromosome rearrangement. PMID- 8464733 TI - Identification of the catalytic and DNA-binding region of the human immunodeficiency virus type I integrase protein. AB - The integrase (IN) protein of the human immunodeficiency virus (HIV) is required for specific cleavage of the viral DNA termini, and subsequent integration of the viral DNA into target DNA. To identify the various domains of the IN protein we generated a series of IN deletion mutants as fusions to maltose-binding protein (MBP). The deletion mutants were tested for their ability to bind DNA, to mediate site-specific cleavage of the viral DNA ends, and to carry out integration and disintegration reactions. We found that the DNA-binding region resides between amino acids 200 and 270 of the 288-residues HIV-1 IN protein. The catalytic domain of the protein was mapped between amino acids 50 and 194. For the specific activities of IN, cleavage of the viral DNA and integration, both the DNA-binding domain and the conserved amino-terminal region of IN are required. These regions are dispensable however, for disintegration activity. PMID- 8464734 TI - Characterization of (GT)n and (CT)n microsatellites in two insect species: Apis mellifera and Bombus terrestris. AB - A set of 52 (CT)n and 23 (GT)n microsatellites in honeybee, 24 (CT)n and 2 (GT)n microsatellites in bumble-bee (n > 6) have been isolated from partial genomic libraries and sequenced. On average, (CT)n and (GT)n microsatellites occur every 15 kb and 34 kb in honeybee and every 40 kb and 500 kb in bumble-bee, respectively. The prevailing categories are imperfect repeats for (CT)n microsatellites in bumble-bee, and perfect repeats for both (CT)n and (GT)n microsatellites in honey-bee. Comparisons with data available in vertebrates indicate a lower proportion of perfect repeats in bees but length distributions are very similar regardless the phylum. This result extends to insects the concept of an evolutionary conservation for quantitative and qualitative characteristics of (CT)n and (GT)n microsatellites. Many (CT)n and (GT)n repeats are surrounded with various types of microsatellites, revealing an associative distribution of short repeat sequences. As expected, a high level of intrapopulational polymorphism has been found with one tested honeybee microsatellite. Also, flanking regions of this microsatellite are similar enough to allow PCR amplification in several other species of Apis and Bombus. PMID- 8464735 TI - Demonstration of Z-d(5BrCGAT5BrCG) and B-d(CGCGATCGCG) form crystal structures in DNA-cobalt hexammine complexes by Kr 647.1 nm excitation of Raman spectra. AB - Cobalt hexammine [Co(NH3)6(3+)] is an efficient DNA complexing agent which significantly perturbs nucleic acid secondary structure. We have employed red excitation (647.1 nm) from a krypton laser to obtain Raman spectra of the highly colored complexes formed between cobalt hexammine and crystals of the DNA oligomers, d(5BrCGAT5BrCG) and d(CGCGATCGCG), both of which incorporate out-of alternation pyrimidine/purine sequences. The Co(NH3)6(3+) complex of d(5BrCGAT5BrCG) exhibits a typical Z-form Raman signature, similar to that reported previously for the alternating d(CGCGCG) sequence. Comparison of the Raman bands of d(5BrCGAT5BrCG) with those of other oligonucleotide and polynucleotide structures suggests that C3'-endo/syn and C3'-endo/anti thymidines may exhibit distinctive nucleoside conformation markers, and tentative assignments are proposed. The Raman markers for C2'-endo/anti adenosine in this Z DNA are consistent with those reported previously for B-DNA crystals containing C2'-endo/anti dA. Raman bands of the cobalt hexammine complex of d(CGCGATCGCG) are those of B-DNA, but with significant differences from the previously characterized B-DNA dodecamer, d(CGCAAATTTGCG). The observed differences suggest an unusual deoxyguanosine conformer, possibly related to a previously characterized structural intermediate in the B-->Z transition. The present results show that crystallization of d(CGCGATCGCG) in the presence of cobalt hexammine is not alone sufficient to induce the left-handed Z-DNA conformation. This investigation represents the first application of off-resonance Raman spectroscopy for characterization of highly chromophoric DNA and illustrates the feasibility of the Raman method for investigating other structurally perturbed states of DNA-cobalt hexammine complexes. PMID- 8464736 TI - The sequence of 28S ribosomal RNA varies within and between human cell lines. AB - The primary structure of 28S ribosomal RNA constitutes a conserved core which is similar among most 23S-like rRNAs and expansion segments which occur at specific positions in the sequence. The expansion segments account for most of the size difference between prokaryotic (archaeal and eubacterial) and eukaryotic rRNAs and they exhibit a sequence variation which is unique among rRNAs. We have investigated the sequence variation of one of the expansion segments, V8, by sequencing a total of 111 V8 segments from 9 different human cell lines and tissues and have found 35 different variants. The variation occur mainly at two 'hot spots' which are separated by 170 nucleotides in the primary sequence but are neighbours in the secondary structure. The sequence of V8 segments varies both within and between human cell lines and tissues. The implications for the evolution of the eukaryotic 28S rRNA are discussed together with possible functions of the expansion segments. We also present a secondary structure model for the V8 segment based on comparative sequence analysis and chemical and enzymatic foot printing. PMID- 8464738 TI - Species-specific differential cleavage and polyadenylation of plasminogen activator inhibitor type 1 hnRNA. AB - Plasminogen activator inhibitor type 1 (PAI-1) is the primary physiologic inhibitor of the naturally occurring plasminogen activators. In higher primates two forms of mature PAI-1 mRNA (3.2 kb and 2.2 kb) arise by alternative cleavage and polyadenylation of PAI-1 hnRNA which is regulated in a tissue-specific fashion in humans. In other mammals only the 3.2 kb mRNA has been detected. The putative downstream polyadenylation site in humans that gives rise to the 3.2 kb PAI-1 mRNA consists of three overlapping copies of the consensus polyadenylation sequence while no consensus polyadenylation sequence is found upstream at a position that could generate the shorter mRNA species. To determine whether differential cleavage and polyadenylation of PAI-1 mRNA is due to species specific differences in trans-acting factors that process PAI-1 mRNA or to the presence of a nonconsensus polyadenylation site acquired recently during primate evolution we prepared plasmids in which the 3' nontranslated region of the human PAI-1 gene or the mouse PAI-1 cDNA was inserted downstream of the neomycin gene in the plasmid pSV2neo. We show that the 3'-nontranslated region of the human PAI 1 gene but not the mouse PAI-1 cDNA conferred alternative cleavage and polyadenylation to the neomycin gene in transfected human Hep G2 cells as well as mouse NIH3T3 and rat L6 cells. PMID- 8464737 TI - Iron regulatory factor expressed from recombinant baculovirus: conversion between the RNA-binding apoprotein and Fe-S cluster containing aconitase. AB - Iron regulatory factor (IRF) is a cytoplasmic mRNA-binding protein that coordinates post-transcriptionally the expression of several important proteins in iron metabolism. Binding of IRF to iron-responsive elements (IRE) in the 5' untranslated region (UTR) of ferritin and erythroid 5-aminolevulinic acid synthase mRNAs inhibits their translation, whereas binding to IREs in the 3' UTR of transferrin receptor (TfR) mRNA prevents the degradation of this mRNA. IRF binds RNA strongly after iron deprivation, but is inactive, yet present, under conditions of high cellular iron supply. Recently, IRF was also shown to have aconitase activity indicating the existence of an Fe-S cluster in the protein. In the current study we expressed human IRF in insect cells from recombinant baculovirus and analysed IRE-binding and aconitase activities under various culture conditions. Newly made apoprotein, synthesized in the absence of iron, was fully active in IRE-binding, but showed no aconitase activity. In contrast, IRF made by cells grown in high iron medium bound RNA poorly, but exhibited high aconitase activity with a Km of 9.2 microM for cis-aconitate. Apo-IRF was converted in vitro to active aconitase by Fe-S cluster-generating conditions, and under the same conditions lost its RNA-binding capacity. These results indicate that the two activities are mutually exclusive and controlled through formation of the Fe-S cluster. PMID- 8464739 TI - Tissue-specific and developmentally regulated alternative splicing of a visceral isoform of smooth muscle myosin heavy chain. AB - Previous work demonstrated that the rabbit smooth muscle myosin heavy chain gene showed sequence divergence at the 25kDa/50kDa junction of the S1 subfragment when compared to chicken gizzard and chicken epithelial nonmuscle myosin. RNase protection analysis with a probe spanning this region detected two partially protected fragments which were not present in RNA from vascular tissue and only found in RNA from visceral tissue. The polymerase chain reaction was used to amplify a 162bp product from primers spanning the putative region of divergence and DNA sequence analysis revealed a seven amino acid insertion not previously detected in other characterised cDNA clones. RNase protection analysis using the PCR product as probe showed that the inserted sequence was expressed exclusively in RNA from visceral tissue. Similar RNA analysis showed that the visceral isoform was not expressed in 20 day fetal rabbit smooth muscle tissues. These results indicated that the new visceral isoform was expressed in a tissue specific and developmentally regulated manner. Genomic DNA sequencing and mapping of the exon-intron boundaries showed that the visceral isoform was the product of cassette-type alternative splicing. The inclusion of a visceral-specific sequence near the Mg-ATPase domain and at the 25kDa/50kDa junction suggests that the visceral isoform may be important for myosin function in smooth muscle cells. PMID- 8464740 TI - Solid-phase synthesis and hybridization properties of DNA containing sulfide linked dinucleosides. AB - Oligodeoxyribonucleotides incorporating non-hydrolyzable dialkyl sulfide linked thymidine dimers (TsT) were synthesized chemically by the solid-phase approach. The sulfide dimer TsT was stable to degradation by snake-venom phosphodiesterase, calf spleen phosphodiesterase, Nuclease P1 and Nuclease S1. Thermal denaturation analysis indicated that the incorporation of TsT dimers into DNA weakened, but did not prevent, binding to complementary DNA and RNA over a wide range of salt concentrations (10 mM to 2 M NaCl). PMID- 8464741 TI - Regulatory elements necessary for termination of transcription within the Ig heavy chain gene locus. AB - Previous experiments have shown that the extent of delta gene transcription during B cell development is regulated primarily at the transcriptional level. We have shown that deletion of a sequence located between the mu and delta coding regions in the Ig heavy chain locus where transcriptional termination has been previously mapped abrogates the termination. Restoration of termination requires reintroduction of this segment as well as sequence elements within the microM poly (A) site which cannot be substituted by the microS poly (A) site. Recognition of the termination site by non-lymphoid cells suggests that initiation of delta transcription in mature B lymphocytes requires the activation of an anti-termination mechanism not yet developed in early B cells. PMID- 8464742 TI - Secondary structure of the small subunit ribosomal RNA sequence of the microsporidium Encephalitozoon cuniculi. PMID- 8464743 TI - The nucleotide sequence of the 25S rRNA-encoding gene from Candida albicans. PMID- 8464744 TI - Nucleotide sequence of a gene encoding a histone-like protein in the archaeon Methanococcus voltae. PMID- 8464745 TI - Analysis of cDNA encoding Drosophila transcription initiation factor TFIIF alpha (RAP74). PMID- 8464746 TI - Rat and chick cDNA clones encoding HMG-like proteins. PMID- 8464747 TI - Wheat TFIID TATA binding protein. PMID- 8464749 TI - S26 ribosomal protein RNA: an invariant control for gene regulation experiments in eucaryotic cells and tissues. PMID- 8464748 TI - An African swine fever virus gene with similarity to bacterial DNA binding proteins, bacterial integration host factors, and the Bacillus phage SPO1 transcription factor, TF1. PMID- 8464750 TI - Sequence of a DNA injection gene from Salmonella typhimurium phage P22. PMID- 8464751 TI - Cloning and sequencing of the genes of beta-glucosyl-HMC-alpha-glucosyl transferases of bacteriophages T2 and T6. PMID- 8464752 TI - A novel method to study DNA replication in vivo in organelles. PMID- 8464753 TI - [201Tl-myocardial scintigraphy (1974-1992): from perfusion defect to detection of viability]. PMID- 8464754 TI - [Quantitative 201Tl-scintigraphy of the lower limb in arterial occlusive disease]. AB - 201Tl scintigraphy is useful in evaluating the hemodynamic consequences of arterial stenoses in arterial occlusive disease. The aim of the present study was to determine normal values for absolute Tl uptake in the lower leg, for the quotient between left and right lower leg uptake as well as for the redistribution pattern after bicycle exercise. We examined as reference 49 patients without clinical evidence of peripheral or coronary artery disease: absolute Tl uptake in the lower leg in anterior scintigraphy (acquisition time: 120 sec) was 5.02 +/- 1.70 counts/pixel (left) and 5.21 +/- 1.53 counts/pixel (right), the quotient between right and left lower leg was 0.85 +/- 0.09 and the redistribution pattern (quotient of the mean activity exercise/rest) 0.82 +/- 0.17 (left) and 0.83 +/- 0.15 (right). The arithmetic mean minus 2 standard deviations was regarded as the lower limit of normal. In 8 patients with mechanical compression of the left femoral artery before injection at least two scintigraphic parameters were abnormal, in 7 patients with angiographically proven peripheral artery disease at least one scintigraphic parameter was below normal. Quantification of Tl redistribution offers diagnostic advantages in bilateral peripheral artery disease. PMID- 8464755 TI - [Immunogenic hyperthyroidism following radioiodine ablation of a focal autonomy]. AB - Immunogenic hyperthyroidism rarely develops after radioiodine elimination of focal autonomous thyroid tissue. We observed this phenomenon in 8 patients between 1989 and 1992. The occurrence of immunogenic hyperthyroidism shortly after elimination of autonomous nodules has not been studied nor is it properly understood. Most studies known today describe the development of autonomous nodules in the course of immunogenic hyperthyroidism or ignore the chronologic order of occurrence. The possibility that immunogenic hyperthyroidism may occur after radioiodine therapy of autonomous nodules, makes a consequent follow-up within the first year following radioiodine therapy mandatory. PMID- 8464756 TI - [The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides]. AB - It is well known that after application of radioactive complexes for tumour diagnosis or therapy, such as 67Ga-citrate or radiolanthanide complexes (167Tm- or 169Yb-nitrilotriacetate, -citrate, -alpha-hydroxyisobutyrate, 90Y-citrate, etc.) activity is accumulated not only in the tumour but also in other organs, above all liver and bone. This is the main obstacle to their medical use. Recently published results encouraged us to use ethylenediaminetetramethylene phosphonate (EDTMP) for the reduction of extratumoural liver activity. The results show that even small amounts of EDTMP (1-2 mg/kg BW) reduce the activity deposition in the liver by about one order of magnitude. EDTMP provoked elimination of activity from tumour, skeleton and other tissues but not to the same extent as from the liver. Tumor/liver activity ratios > 5 are achievable in this manner. PMID- 8464757 TI - [The effect of bone-seeking metal salts on the biodistribution of tumor-seeking heavy metal complexes]. AB - This work attempted to overcome the problem of unwanted bone radioactivity after injection of tumour-affine heavy-metal compounds (prototype 169Yb-citrate) by pre application of stable yttrium- and calcium-compounds into tumour-bearing mice in doses of 1 mg metal/kg body weight. The pre-application of stable yttrium and calcium resulted in a smaller bone radioactivity. The most favourable results were achieved by injecting the metal salts simultaneously at or within 5 h before the 169Yb-citrate. On the other hand a strong radioactivity increase in the RES (liver and spleen) by a factor of 2 to 4 was observed after yttrium preapplication. PMID- 8464758 TI - [Determination of renal clearance with only a single access for injection and blood extraction]. AB - An injection technique was developed to administer radioactivity to children and adults and to withdraw plasma samples through the same venous line. The error in clearance estimation due to "contamination" was smaller than that caused by the timing of blood sampling or the type of algorithm used for clearance calculation. PMID- 8464759 TI - [The trend distribution quotient, a new tool for evaluating renal perfusion scintigraphy using 99mTc-DTPA following renal transplantation]. AB - We developed a new quantitative concept in dynamic renal transplant imaging, the Trend Distribution Ratio, and tested its diagnostic usefulness in 137 examinations. This ratio is an expression of the distribution of blood flow velocity in different areas of the kidney. With regard to the differential diagnosis between acute tubular necrosis and the various forms of rejection we arrived at a sensitivity of 0.83 and a specificity of 0.54. A differentiation between the various histological types of rejection has not yet been possible. PMID- 8464760 TI - [A simple method of digitizing analog scintigrams for quantification and digital archiving]. AB - This study was undertaken to evaluate a quick, reliable and cheap method of digitizing analog scintigrams. 40 whole-body bone scintigrams were obtained simultaneously in analog and genuine digital format. The analog scans on x-ray film were then digitized secondarily by three different methods: 300 dpi flat-bed scanning, high-resolution camera scanning and camcorder recording. A simple exposure approach using a light box, a cheap camcorder, a PC and image grabber hard- and software proved to be optimal. Visual interpretation showed no differences in clinical findings when comparing the analog images with their secondarily digitized counterparts. To test the possibility of quantification, 126 equivalent ROIs were drawn both in the genuine digital and the secondarily digitized images. Comparing the ROI count to whole-body count percentage of the corresponding ROIs showed the correlation to be linear. The evaluation of phantom studies showed the linear correlation to be true within a wide activity range. Thus, secondary digitalization of analog scintigrams is an easy, cheap and reliable method of archiving images and allows secondary digital quantification. PMID- 8464761 TI - [Radiation exposure in diagnostic nuclear medicine: risk comparisons on the basis of effective doses]. AB - The hypothetical risk of medical radiation exposure is often extrapolated to large population groups using arbitrary assumptions. To assess risk and benefit of diagnostic nuclear medicine and roentgenology, estimation of individual loss of life expectancy should be preferred. Employing ICRP 60 figures, diagnostic medical radiation exposure yields effective doses which commonly lie below or within the range of annual exposure from natural radiation (1-6 mSv). On an average, the individual medical exposure in Germany is estimated to be between 1 and 2 mSv which--extrapolated to total lifespan--leads to a hypothetical loss of life expectancy of 20-40 days. In the light of the rapid increase of life expectancy due to progresses in medical diagnostics and treatment after the introduction of X-rays, this figure is negligibly small. PMID- 8464762 TI - [Topodiagnosis of Creutzfeldt-Jakob disease using HMPAO-SPECT]. AB - An 80-year old female presented with early stage Creutzfeldt-Jakob disease with clinical, neurophysiological and neuropathological findings suggesting a focal involvement of the brain. HMPAO SPECT disclosed asymmetries of regional cerebral perfusion, thus suggesting that it may be a further diagnostic instrument in this disease. PMID- 8464763 TI - [The "white hole" phenomenon--a potential functional parameter in non-gated 201Tl myocardial scintigraphy]. AB - In 50 patients with a "white hole" in their scintigram--among them 44 patients with a history of myocardial infarction--the relation between its relative volume and the ventriculographically determined ejection fraction was studied retrospectively. A relative volume of the "white hole" larger than 13.7% showed a specificity of 93% and a sensitivity of 45% for a decreased ejection fraction and had a significant correlation of r = -0.54 (alpha = 0.01) with the ejection fraction. Thus the relative volume of the "white hole" derived automatically from 201Tl-SPECT is an easy-to-determine additional parameter which allows an at least semiquantitative statement about the function of the left ventricle. PMID- 8464764 TI - Whither academic orthopedic integrity? PMID- 8464765 TI - A clinical and comparative biomechanical evaluation of proximal femoral osteotomy fixation in children. AB - This study compared the biomechanical characteristics of a 90 degrees infant blade plate construct and anteriorly applied 120 degrees angled plate construct in response to an axial compression load. The blade plate construct stiffness was three times greater than the angled plate construct (238.9 vs 85.7 N/deg). Four degrees failure load was also significantly higher for the blade plate. Despite inferior biomechanical characteristics, the 120 degrees angled plate functioned very satisfactorily in a retrospective clinical review of 21 proximal femoral varus osteotomies. The authors conclude that the 120 degrees angled plate has practical benefits in terms of ease of insertion and intraoperative adjustability which may outweigh its biomechanical inferiority. PMID- 8464766 TI - Stability in relation to humeral head retroversion after surgical treatment of recurrent anterior shoulder dislocations. AB - This study reports the influence of the retroversion angle on the postoperative stability in 50 patients operated on for recurrent shoulder dislocations. Fifty two shoulders were reviewed by radiographic and clinical examinations. Particular attention was focused on humeral head retroversion, shoulder stability, and range of motion in relation to surgical technique. The retroversion angle was significantly reduced in 30 of 47 shoulders, for which satisfactory radiographs could be achieved. Mean humeral head retroversion was 24 degrees for both dominant and nondominant shoulders. Forty-eight of 52 reexamined shoulders became stable. Four had remaining instability following a Putti-Platt procedure, with a mean retroversion angle of 18 degrees. A reduced humeral head retroversion is therefore proposed as an important factor in creating instability, and may be one explanation for failed stability after soft tissue repair. Irrespective of the type of surgical procedure (Bristow or Putti-Platt), there was a significant decrease in range of shoulder rotation in the operated shoulder compared to the contralateral stable shoulder and to reference values for normal controls. However, decreased rotation was not found to impair shoulder function, and 48 of the 50 reexamined patients generally improved after surgery. PMID- 8464767 TI - Reinfusion of filtered postoperative orthopedic shed blood: safety and efficacy. PMID- 8464768 TI - Rehabilitation following reconstruction of the anterior cruciate ligament. AB - A closely supervised rehabilitation program is mandatory if maximum benefit is to be derived from anterior cruciate ligament (ACL) reconstruction. The author describes a postoperative rehabilitation protocol based on kinesiologic, histologic, and biomechanical factors affecting the ACL. PMID- 8464769 TI - Radial head dislocation following septic arthritis of the elbow. PMID- 8464770 TI - The distal oblique comminuted tibia fracture. PMID- 8464771 TI - Non-cemented total hip replacement for metastatic disease. PMID- 8464772 TI - Systemic mastocytosis with pathologic fractures of distal long bones. PMID- 8464773 TI - Arthroscopic suture fixation of displaced tibial eminence fractures. PMID- 8464774 TI - Chondroblastoma. PMID- 8464775 TI - Rehabilitation following arthroscopic subacromial decompression. PMID- 8464776 TI - Radiologic case study. Fractures of the proximal humerus. PMID- 8464777 TI - Answer please. Cavernous lymphangioma of the hand. PMID- 8464778 TI - Abnormal pulmonary bombesin immunoreactive cells in Wilson-Mikity syndrome (pulmonary dysmaturity) and bronchopulmonary dysplasia. AB - Wilson-Mikity syndrome (WMS) is a disorder of uncertain origin. It is sometimes considered a variant of bronchopulmonary dysplasia (BPD), but it lacks the characteristic microscopic stigmata of destruction and fibrosis caused by the barotrauma and oxygen toxicity of ventilator support. Conventional clinical and autopsy studies of WMS have failed to identify the underlying pathophysiology. This study evaluated bombesin-containing pulmonary neuroendocrine (PNE) cells in eight WMS cases, seven cases of BPD, and five controls, using the immunoperoxidase technique. The PNE cells were quantified by established morphometric techniques. The percentage of airways containing PNE cells in WMS (mean, 85.56%) was similar to that in the controls (mean, 82.6%) but significantly greater than that in BPD (mean, 21.28%) (p < .001). Measurement of intraepithelial PNE cell cytoplasm within the bombesin-immunopositive airways demonstrated apparent PNE cell hyperplasia in both WMS and BPD. Prominent numbers of PNE cells were also present in the respiratory bronchioles and alveolar units in WMS. The increased PNE cells in WMS may reflect chronic hypoxia from hypoventilation and or autonomic dysfunction. The profile in BPD may reflect a similar pathophysiology but complicated by ventilator-induced injury to airway epithelium. PMID- 8464779 TI - Maldescent of the thymus: 34 necropsy and 10 surgical cases, including 7 thymuses medial to the mandible. AB - Among 3236 pediatric necropsies over 23 years, abnormal position of thymic tissue was recorded in 34 cases. Cardiac anomalies, predominantly those seen in DiGeorge syndrome, were present in 24; 3 had noncardiac anomalies only, 4 had other diseases, and 3 were sudden infant deaths. Mediastinal thymic tissue was absent in 22 cases, small or unilateral in 7, and normal in 5. The maldescended thymic tissue was unilateral in 18, bilateral in 11, and multiple on one or both sides in 5. It was situated near the thyroid gland in 19, lower in the neck in 6, and higher in 9, including 7 medial to the submandibular salivary gland and 1 at the base of the skull. The maldescended tissue approached the size of a normal lobe of thymus in eight and was 2.4 to 0.1 cm in the remainder. Over the same period, in only two cases was no thymic tissue found. Among 68,000 surgical specimens over 40 years, there were 10 cases of ectopic thymus in the neck, including 1 cutaneous and 4 cystic. This frequency of thymic tissue in the neck may explain why lymphoid tissues are sometimes relatively normal in cases of absent mediastinal thymus and behooves a search in the submandibular salivary gland region and higher before diagnosing thymic agenesis. PMID- 8464780 TI - Histochemistry of the atrioventricular conducting system during postnatal development. AB - The atrioventricular conduction system of 27 infants coming to autopsy was examined by histochemical methods. Twenty one were sudden infant deaths; six were explained deaths. A decrease of oxidoreductases and hydrolases activities was found in clusters of conducting cells protruding from the atrioventricular (AV) node and His bundle left into the collagen of the septum. These findings reflect regressive changes connected with reduction of the AV conducting system during postnatal development. PMID- 8464781 TI - Syndromal associations of common origin of the carotid arteries. AB - The term "common origin of the carotid arteries" (COCA) has been proposed to replace the older terms "origin of the left carotid artery from the innominate stem" and "bicarotid trunk with anomalous right or left subclavian artery." These anatomic patterns are usually reported to occur in about 11% of whites and 20-25% of blacks and have been reported to have increased frequency in patients with esophageal atresia-tracheoesophageal fistula, DiGeorge anomaly, and anomalous origin of the left coronary artery from the pulmonary artery. COCA is a significant, if not invariant, feature of the great arteries in the condition usually called in the more recent literature "anomalous origin of the innominate artery," the most frequent cause of symptomatic tracheal compression by anomalous systemic arteries. Analysis of associations of COCA with various other congenital cardiovascular lesions showed, in addition, significant association with congenital polyvalvular disease, truncus arteriosus, aorticopulmonary window, trisomy 13, 18, and 21 syndromes, acrocephalosyndactyly (especially Apert syndrome), tetralogy of Fallot not associated with DiGeorge anomaly, and clinical Noonan phenotype. Pentalogy of Cantrell was associated with no increase in incidence of COCA. PMID- 8464782 TI - Branching patterns of right pulmonary artery in cardiovascular anomalies. AB - The branch of the right pulmonary artery (RPA) to the upper lobe of the right lung (RUL), the truncus anterior of the RPA, and the pars anterior of the left pulmonary artery, which supplies the left upper lung lobe (LUL), were demonstrated by both dissection of postmortem specimens and angiography for 20 infants and children, by angiography only for 57, and by specimen dissection only for 59 (total 136). In posteroanterior angiograms, the RUL artery branches from the RPA near the right lateral border of the vertebral column, while the LUL artery or arteries arise more laterally, near the left midclavicular plane. This pattern is reversed in situs inversus (eight patients studied). Thirty-nine patients in other categories of congenital cardiovascular disease showed an abnormal RUL or LUL arterial pattern, including pulmonary isomerism, right lung type (RUL artery pattern present bilaterally, 12 patients); pulmonary isomerism, left lung type (RUL artery pattern absent bilaterally, 11 patients); scimitar syndrome (RUL artery pattern normal, 1 patient; absent bilaterally, 4 patients); and left pulmonary artery sling (RUL artery normal, one; hypoplastic, one; absent, two patients). Five patients with tetralogy of Fallot (TOF) with right aortic arch (RAA) and 1 of 15 with RAA not TOF or situs inversus showed a relatively large RUL artery arising more laterally than usual. Three of six patients with double outlet right ventricle had the LUL artery larger than usual plus two accessory RUL arteries, and one patient with crossed pulmonary arteries showed a similar pattern. Two patients with single ventricle had an RUL artery of normal pattern although the RUL bronchus was absent, and one patient with single ventricle and situs inversus had a comparable pattern in the left lung. The ease of demonstration of the right and left upper lobe branches of the pulmonary artery by dissection or angiocardiography warrants greater attention to their patterns in patients with congenital cardiovascular disease. Dissociation of upper lobe bronchial and vascular patterns is unusual and may also be of diagnostic value. PMID- 8464783 TI - Intestinal neuronal density in childhood: a baseline for the objective assessment of hypo- and hyperganglionosis. AB - In the absence of reliable baseline data for normal neuron density in the intestine, the diagnosis of hypo- and hyperganglionosis is purely subjective. This study has established the normal neuron density by neuron counts in paraffin sections taken both transversely (transverse sections, TS) and longitudinally (longitudinally sections, LS) in relation to the long axis of normal postmortem jejunum, ileum, and colon from 21 children (aged 4 weeks to 10 years). Intestine from two adults (aged 16 and 42 years) and colon alone from a further six adults (aged 16 to 83 years) were also studied. The mean density values in childhood were for jejunum 3.6/mm (TS), 3.7/mm (LS); for ileum 4.3/mm (TS, LS); and for colon 7/mm (LS), 7.7/mm (TS). The proximal margins of surgically resected colons from six patients with Hirschsprung's disease and one patient with suspected isolated hypoganglionosis were also analyzed and the neuron densities compared with the established postmortem data. Neuron density values outside two standard deviations from the postmortem mean were shown to correlate with continuing pseudo-obstructive symptoms in these patients. PMID- 8464784 TI - Renal tubular dysgenesis: a description of early renal maldevelopment in siblings. AB - A family is described in which three siblings, born after pregnancies complicated by oligohydramnios, developed renal abnormalities. In the first infant, of 38 weeks gestation, histologic changes were nearly identical to those found in renal tubular dysgenesis (RTD), a recently identified disorder characterized by the absence of recognizable renal proximal tubules. Additional findings include bilateral renal vein thrombosis and marked calvarial bone hypoplasia. The other two gestations were 20 and 22 weeks long. Renal histology in these cases showed nonspecific abnormalities with focal tubular dilatation, decreased tubule formation, and increased interstitial connective tissue. Clearly recognizable proximal tubules were present, though decreased in number. The latter two gestations described herein are the earliest examined in a family with RTD and the renal abnormalities may represent early changes seen in this disorder. PMID- 8464785 TI - An infant with X-linked myotubular myopathy. PMID- 8464786 TI - Divergent genetic selection for incidence of tibial dyschondroplasia in broilers at seven weeks of age. AB - Selection for a high (H) or low (L) incidence of tibial dyschondroplasia (TD) at 7 wk of age was practiced for four generations in broiler breeders using low intensity x-ray imaging (Lixiscope) for TD diagnosis. As a result, broiler lines with H or L incidence of TD at 7 wk of age were developed keeping a randomly selected control (C) broiler line. A total of 4,232 chicks were hatched representing 172 sires and 612 dams over four generations for the H, L, and C lines. The TD scores at 7 wk were collected on 4,056 broilers. Incidence of TD at 4 and 7 wk of age were studied in the C, H, and L lines of broilers. Direct response to selection in the H and L lines were estimated per generation and per weighted cumulative selection differential (WCSD). Total WCSD deviation from the C line for incidence of TD at 7 wk of age was 1.496 and -.42 units for the H and the L lines, respectively. The response per generation for incidence of TD at 7 wk of age for the H line was .153 +/- .028 units. The realized heritability for the H line for incidence of TD at 7 wk of age was .437 +/- .065. The incidence of TD was not significantly decreased in the L line at 7 wk of age. PMID- 8464787 TI - Exclusion of broiler breeder females from male feeders with a male only grill. 1. Behavioral and technical aspects of design and development. AB - A series of experiments was conducted in order to develop a feeder grill that would allow broiler breeder males, but not females, to eat. Females are typically excluded from male feeders by increasing the height of the feeder. However, male feeder heights that exclude most females increase the time required for males to consume a given amount of feed 19 to 60%. Typical male feeder height from floor to feeder pan lip in commercial practice is 55 cm, which is about the distance from floor to the head of the male in an erect posture. Females measure about 40 cm in an erect posture. Because the necks of males (8.0 cm) are longer than those of females (6.3 cm), the lip of male feeder pans was extended horizontally 12.7 cm with a wire mesh on the assumption that females could not stretch their necks enough to reach the feed. However, the females learned quickly to perch on the extended lip and eat. Total exclusion of females from the male feeder, regardless of feeder height, was achieved by placing a horizontal upper mesh 5.6 to 10.2 cm above the extended lip, and connecting the upper mesh to the lower extended lip of the feeder with vertical bars spaced 5.1 cm apart. The horizontal upper mesh prevented perching by females and the 5.1-cm spacing of the vertical bars allowed males but not females to reach the feed by inserting their heads and necks up to their shoulders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464789 TI - Fibronectin synthesis in the harderian gland of the chicken. AB - Immunoelectron microscopic staining with a monoclonal antibody against fibronectin demonstrated the presence of this extracellular matrix glycoprotein in the avian Harderian gland. Fibronectin was detected as a component of the electron-dense material, which has been observed both between the epithelial cells lining the ducts of the gland and between the lymphoid cells within the subepithelial lymphoid tissue. Additionally, intracellular fibronectin was detected in the rough endoplasmic reticulum, Golgi complex, and secretory vacuoles in the cytoplasm of a cell, showing the ultrastructural features of a myofibroblast. These findings indicate that the Harderian gland myofibroblasts secrete and release fibronectin into the extracellular matrix. PMID- 8464788 TI - Effects of feeding Fusarium moniliforme culture material, containing known levels of fumonisin B1, on the young broiler chick. AB - The effects of feeding Fusarium moniliforme culture material, containing known concentrations of fumonisin B1 (FB1), were studied in broiler chicks. Day-old chicks were allotted randomly to dietary treatments containing 0, 1.02, 2.04, 3.06, 4.08, 5.10, 6.12, and 7.14% fumonisin culture material (FCM). These levels of FCM supplied 0, 75, 150, 225, 300, 375, 450, and 525 mg of FB1/kg of feed. Each dietary treatment was fed to four pen replicates of six birds each for 21 days. Chicks fed FCM that supplied 450 and 525 mg FB1/kg diet had lower (P < .05) feed intakes and BW gains; increased (P < .05) liver and kidney weights; and increased (P < .05) mean cell hemoglobin, and mean cell hemoglobin concentrations. Compared with controls, chicks fed FCM had increased (P < .05) free sphinganine levels and sphinganine:sphingosine ratios. Treatment-associated histological lesions were only observed in the liver of chicks fed diets containing FCM that supplied 225 mg FB1/kg or higher. Diets containing FCM that supplied levels as low as 75 mg FB1/kg affected the physiology of chicks by increasing free sphinganine levels and sphinganine:sphingosine ratios. Because inhibition of sphingolipid biosynthesis has been hypothesized as the mechanism of action of FB1, this suggests that diets containing 75 mg FB1/kg FCM may be toxic to young broiler chicks. PMID- 8464790 TI - Vitamin profiles of eggs as indicators of nutritional status in the laying hen: riboflavin study. AB - Two experiments determined the effect of dietary riboflavin supplementation on egg yolk and albumen riboflavin concentrations, egg production, egg weight, shell thickness, hen weight, hatchability, incidence of clubbed down, and incidence of hemorrhagic embryos. In the first experiment, hens were fed rations containing 1.55, 2.20, 4.40, and 8.80 mg of riboflavin/kg of diet for 27 wk. Significant (P < .05) depressions in both yolk and albumen riboflavin concentrations were noted at the two lower riboflavin levels after 1 wk. Egg production, egg weight, hatchability, and hen weight were all significantly depressed by the two lower riboflavin levels later in the experiment when compared with the two higher levels. Results indicate that egg riboflavin concentrations are related to important production parameters that may be used to predict future dietary riboflavin inadequacies. In the second experiment, hens were fed either an unsupplemented diet or a riboflavin-adequate diet. Measurements of egg albumen riboflavin content, egg production, hatchability, and embryo abnormalities were made twice each week. Results showed depressed albumen riboflavin concentrations and hatchability and increased incidence of hemorrhagic embryos and clubbed down without changes in egg production during the 4- to 7-day period following feeding of the unsupplemented diet. These results show that low albumen riboflavin content immediately affect hatchability and embryonic development. The estimated minimum critical albumen riboflavin concentrations needed to support maximum reproductive function are between 1.9 and 2.9 micrograms of riboflavin/g of egg albumen. These critical values might be used to evaluate riboflavin status of laying and breeding flocks. PMID- 8464791 TI - Effects of lighting pattern and dietary tryptophan supplementation on growth and mortality in broilers. AB - The effect of lighting pattern and supplementation of the diet with Trp on growth and mortality of male broiler chickens was evaluated in three experiments using 2,392, 2,608, and 2,400 chickens, respectively. There were two lighting treatments, either a constant 23 h of continuous light/24-h period or an increasing photoperiod lighting system, i.e., 0 to 3 days, 23 h light (L):1 h dark (D); 4 to 14 days, 6L:18D; 15 to 21 days, 10L:14D; 22 to 28 days, 14L:10D; 29 to 35 days, 18L:6D; 36 to 42 days, 23L:1D. The design was a completely randomized 2 x 2 factorial, with four replicates per treatment. In the first two experiments, a starter diet with or without .2% supplemental L-Trp (feed grade) was fed from 0 to 3 wk of age and a finisher diet with or without .2% supplemental Trp was fed from 3 to 6 wk of age. In the third experiment, the level of supplemental Trp was .4% in the starter and finisher diet. Birds raised on the increasing light pattern consumed less feed during the first 3 wk, were lighter in weight at 3 wk, and had lower feed:gain ratios (P < .001) than their counterparts on constant light. By market age (6 wk) they had similar body weight but feed intake was significantly (P < .05) lower in all experiments, and feed:gain ratio was significantly lower in these birds in Experiment 3 (P < .05) than in their counterparts on constant light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464792 TI - Evaluation of two novel biochemicals on plasma and egg yolk lipid composition and laying hen performance. AB - PD132301-2, an inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT; EC 2.3.1.26), and 1-stearylboronic acid (SBA), a fatty acid analogue, were orally administered to White Leghorn hens in separate experiments to evaluate their effects on layer performance and plasma and egg yolk lipids. Five 60-wk-old hens each were fed either a corn-soybean meal basal layer ration, or the basal diet supplemented with .0121, .0363, or .1089% PD132301-2. In a second experiment, 12 37-wk-old hens each were fed either a basal layer ration, or the basal diet supplemented with .20 or .40% SBA. The duration of the experiments were 21 and 16 days, respectively. Neither compound significantly affected hen-day production, egg weight, yolk weight, BW gain, feed consumption, feed efficiency, plasma total cholesterol and triglyceride concentrations, or egg yolk cholesterol content. PD132301-2 had no effect on yolk fatty acid profiles, and C22:6n3 was the only fatty acid altered by SBA. Although 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been successful in reducing egg cholesterol, ACAT inhibitors and fatty acid analogues apparently hold little promise in this regard. The results of the present work also support the concept that, in order to pharmacologically alter the cholesterol content of eggs, direct inhibition of key enzymes in the cholesterol biosynthetic pathway is necessary. PMID- 8464793 TI - Dietary addition of cellular metabolic intermediates and carcass fat deposition in broilers. AB - Ninety-six 1-day-old male broilers were fed a diet containing 0, 2, 4, 6, 8, or 10% of a 1:1 mixture of pyruvic acid (PY) and dihydroxyacetone (DH) for ad libitum consumption for 42 days. Feed intake, body weight gain, and feed efficiency decreased linearly (P < .001) with increasing levels of PY and DH. There were no significant differences among treatments for abdominal fat percentage. Carcass chemical analysis revealed small but significant (P < .05) differences among dietary treatments for protein and fat percentages. In a second experiment, 192 1-day-old male broilers were fed diets containing 5% of PY, lactic acid (LA), citric acid (CI), DH, or glycerol (GY) or mixtures (1:1) of DH or GY in combination with each organic acid. Bird performance was impaired (P < .05) by PY or CI but not by DH or GY. Lactic acid reduced (P < .05) feed intake by 9% without affecting weight gain. Lactic acid plus DH, CI plus DH, and CI plus GY mixtures decreased (P < .05) bird performance but other combinations had no effect. Pyruvic acid or CI decreased abdominal fat and carcass lipid percentages. Dihydroxyacetone increased (P < .05) carcass lipid percentage and GY increased (P < .05) abdominal fat percentage. Lactic acid plus DH increased (P < .05) carcass lipid percentage. Only PY and CI decreased carcass fat deposition, but they also impaired broiler performance. PMID- 8464794 TI - Evaluation of egg injection of folic acid and effect of supplemental folic acid on hatchability and poult weight. AB - Two experiments were conducted with Large White turkey hens housed individually in cages in a conventional house. In Experiment 1, three dietary treatments were used: an unsupplemented practical corn-soybean meal basal diet; the basal diet supplemented with 2.64 mg folic acid/kg of diet; and the basal diet supplemented with 5.51 mg folic acid/kg of diet. Eggs from hens fed 2.64 mg folic acid/kg of diet were injected with folic acid in 20 injection trials over two production cycles. The response data from dietary supplemental folic acid were analyzed on a production period basis using all of the hens, and on a subset of hens producing eggs in each production period, for hatchability of fertile eggs and poult weight. The response patterns in each case were similar. Incremental dietary supplemental folic acid levels produced a positive linear response pattern on the transfer of folic acid in eggs, but did not result in a hatchability increase over the unsupplemented folic acid basal diet. Hatchability increase did not occur for eggs injected at 25 days of incubation with 19.3 micrograms folic acid per egg in 20 injection trials over two cycles of production. The results of the study indicate that hatchability is not increased in turkey eggs from hens fed supplemental folic acid or with egg folic acid injections. However, egg and poult weights were significantly increased (P < .05) in eggs containing 6 to 7 mg folic acid/g of dried egg, from hens fed 5.51 mg folic acid/kg of diet. PMID- 8464795 TI - The relationship between muscle growth and the growth of different fiber types in the chicken. AB - A relationship of muscle growth to fiber growth was investigated histochemically and allometrically in the chicken from 1 to 35 wk of age. Muscle fibers were classified into three types (I, IIA, and IIB) based on the reactivities for myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide dehydrogenase. Fiber type composition widely varied in the four muscles examined in this study. Longus colli dorsalis contained all three types. The Pectoralis was composed only of IIB fibers. The caudal portion of Femorotibialis medius was made up of Type I and IIA fibers. The caudal Iliotibialis lateralis and the cranial portion of Femorotibialis medius were composed of two types, IIA and IIB. These latter two muscles showed a progressive increase of Type IIA fibers and decrease of Type IIB fibers with advancing age. Two processes controlling muscle growth were elongation and enlargement of muscle fibers. The elongation of muscle fibers stops by 15 wk of age, coincident with the cessation of bone growth. However, the enlargement of muscle fibers, the increase in diameter of muscle fibers, continued until 35 wk of age. The rate of enlargement of muscle fibers varied by muscle and fiber type. In general, greatest growth occurred in Type IIB fibers of hindlimb muscles. PMID- 8464796 TI - Fragmentation, tenderness, and post-mortem metabolism of early-harvested broiler breast fillets from carcasses treated with electrical stimulation and muscle tensioning. AB - Two 72-bird trials were conducted to determine the effects of 15 s electrical stimulation (ES) (440 V, 2 s on and 1 s off) and prechill muscle tensioning (MT) on fragmentation, tenderness, and post-mortem metabolism of early-harvested (1 h post-mortem) broiler breast fillets. Compared with controls, all treatments increased sarcomere length and decreased shear value. Electrical stimulation reduced muscle pH values. Histological examination of samples from fillets harvested early and then aged 24 h revealed that all treatments increased fiber disruption compared with controls. Both fragmentation and excessive sarcomere shortening prevention were important to the improvement in fillet tenderness associated with the ES and MT treatments. PMID- 8464797 TI - Variations in muscle chemical composition, pH, and protein extractability among eight different broiler crosses. AB - Variations in muscle chemical composition, pH, and protein extractability were studied using male broilers of eight different genetic crosses of commercial strains. Three replicate groups of 24 birds of each cross were grown in floor pens using commercial corn-soybean meal diets. At 8 wk of age, three birds per replicate, weighing within 5% of the pen average, were slaughtered, scalded, defeathered, eviscerated, and chilled in ice slurries overnight. Muscles were excised from breasts and thighs, and trimmed of skin and external fat. Proximate analysis was conducted using ground muscle pooled within replicate groups. Breast muscle of all strain crosses contained more (P < or = .05) total protein (ranging from 20.7 to 23.6%) and moisture (74.6 to 75.9%), and less fat (1.0 to 2.0%) than thigh muscle, which contained 18.1 to 21.3% protein, 72.8 to 73.8% moisture, and 5.0 to 7.2% fat. The pH of breast muscle was lower (P < or = .05) than that of thigh muscle for four of the eight strains, and protein extractability of breast muscle was greater (P < or = .05) than that of thigh muscle for all strains. There were significant differences among strains in chemical composition, pH, and protein extractability for both breast and thigh muscles. The correlation between percentage protein and fat was positive in breast (r = .72, P < .05) and negative in thigh muscle (r = -.77, P < .05). However, no significant correlations were observed between the chemical constituents of breast muscle with the respective constituents of thigh muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464798 TI - Effect of two stunning voltages on blood loss and objective texture of meat deboned at various post-mortem times. AB - Two experiments were conducted to determine the effect of different stunning voltages on the objective texture of the Pectoralis major muscles deboned at various post-mortem times. Broilers were stunned at either 50 or 200 V alternating current (VAC) for 10 s in a brine stunner. The artery and vein on one side of the neck were severed, blood collected for 90 s, and blood loss calculated as percentage of live weight. Carcasses were then processed under simulated commercial conditions. In the first experiment, the right and left Pectoralis major muscles were excised at 1 and 2 h post-mortem respectively, weighed, vacuum-sealed in plastic bags, and held overnight at 2 C. In the second experiment, the Pectoralis major muscles were excised at 4 h post-mortem and held overnight at 2 C. The muscles were then heated at 85 C for 30 min, equilibrated to room temperature, and prepared for Warner-Bratzler shear analysis. The stunning treatments did not significantly affect blood loss, which averaged 2.86 and 2.64% for 50 and 200 VAC, respectively. Birds subjected to the 50 VAC treatment had a mean shear value of 7.3 kg, which was significantly lower (P < .05) than the mean shear value of 10 kg for birds subjected to the 200 VAC treatment for muscles excised 2 h post-mortem. The use of 200 VAC for stunning could be used without any detrimental effect on the cooked meat as long as the standard deboning time of 4 h was maintained. PMID- 8464799 TI - Research note: effect of age on the yolk to albumen ratio in chicken eggs. AB - The effect of age on the yolk:albumen (Y:A) ratio was studied for eggs obtained from Hy-Line W36 and Arbor Acres hens. Albumen weight was more closely associated with egg weight (EW) than yolk weight for both commercial layers and broiler breeder hens. A small positive relationship between EW and Y:A ratio was found. A significant increase in Y:A ratio was evident in older flocks from both breeds. PMID- 8464800 TI - Research note: effects of perfluorochemical diluent additives on fertilizing capacity of turkey semen. AB - The perfluorochemicals (PFC) have a high capacity for dissolving oxygen and carbon dioxide. Two experiments were conducted using PFC as diluent components to assess their effect on the fertilizing capacity of, and the hatchability of eggs from hens inseminated with, turkey semen stored for 30 min or 3 h. Two PFC were tested for the 30-min experiment: perfluorohexane (FC-72) and perfluorobutyltetrahydrofurane (FC-80). For the 3-h experiment, these PFC plus bis-1,2-(F-butyl)-ethene (F-44E) were studied. The PFC were emulsified with an equal volume of a standard aqueous salt diluent, Beltsville Poultry Semen Extender (BPSE). The BPSE alone was used as a control in both experiments. Semen was diluted 1:2 with oxygen-saturated extender and stored in closed tubes at 20 to 30 C prior to insemination. For the 30-min study, PFC diluents resulted in fertility rates comparable to (FC-72) or significantly greater than (FC-80) BPSE alone (P < or = .05). There was no significant difference in hatchability due to any semen treatment. When semen was stored for 3 h, PFC diluents resulted in comparable (FC-80) or significantly higher (F-44E and FC-72) fertility and hatchability rates. Significantly lower embryonic deaths at Day 10 of incubation were noted for all PFC diluents. These findings provide evidence that PFC emulsions are not toxic and prolong fertilizing capacity of turkey sperm during short-term storage, and suggest that providing oxygen carriers such as PFC in semen diluents may be beneficial. PMID- 8464801 TI - Research note: responses of laying hens on saline drinking water to dietary supplementation with various zinc compounds. AB - Production variables, eggshell defects, eggshell quality, the concentration of calcium-binding protein (CaBP), and the activity of carbonic anhydrase (CA) in the shell gland mucosa were determined in hens receiving town water (10 mg Na/L), or town water supplemented with 2 g NaCl/L (796 mg Na/L). Five treatments were examined. Control hens received town water and a proprietary layer mash containing .17% Na. The remaining four treatments received the water containing NaCl (2 g/L). Hens of Treatment 2 were fed the proprietary layer mash and those of Treatments 3, 4, and 5 received, respectively, the layer mash containing supplements of Zn-methionine (Zinpro-200; .5 g/kg), Zn sulfate (ZnSO4.7H2O; .46 g/kg), or chelated Zn-EDTA (.54 g/kg) to supply the same concentration of Zn (.1 g/kg). The treatments were applied for 6 wk. Hens receiving the saline drinking water without any dietary Zn supplement produced significantly (P < .05) more eggs with shell defects than hens receiving the town water. This increase in the incidence of eggshell defects was associated with significant reductions in eggshell breaking strength, the concentration of CaBP, and the activity of CA. Supplementing the saline drinking water with any of the three Zn compounds significantly reduced the incidence of eggshell defects and in some cases improved shell breaking strength, the concentration of CaBP, and the activity of CA. PMID- 8464802 TI - Research note: effect of diet density and pelleting on productive parameters of Japanese quail. AB - An experiment was conducted to determine the response of growing Japanese quail to two dietary energy levels, high (3,200 kcal ME/kg) versus low (3,000 kcal ME/kg), and two forms of presentation, mash versus pellet. Seven thousand, two hundred day-old Japanese quail (Coturnix coturnix japonica) were randomly distributed into 24 floor pens containing 300 quail each. The experiment was divided in two phases: starter (until 2 wk of age) and finisher (Days 14 to 33). Weight gain was less (P < .05) for quail fed the low-energy mash diet than for those on other treatments. Feed consumption increased (P < .001) when low-energy and mash diets were fed. Metabolizable energy consumption was greater with the mash diets. Feed conversion improved (P < .001) when high-energy and pelleted diets were fed as compared with low-energy and mash diets, respectively. Results indicated that daily gain and feed conversion of quail fed the low-energy, pelleted diet equaled those of quail fed the high-energy mash diet. Pelleting improved the caloric efficiency of gain by quail. Quail seemed to adjust caloric intake according to the energy level of the diet. PMID- 8464803 TI - Solid-state nuclear magnetic resonance spectroscopy: theory and pharmaceutical applications. AB - The theory of solid-state nuclear magnetic resonance (NMR) spectroscopy is reviewed, with specific discussions of magnetic interactions in the solid state. Each magnetic interaction (Zeeman, dipole-dipole, chemical-shift, spin-spin, and quadrupolar) is addressed and manifestations of these interactions in the solid state NMR spectrum are explained. The techniques of high-power decoupling, magic angle spinning, and cross-polarization, used to acquire highly resolved solid state NMR spectra, are also illustrated. Application of solid-state NMR to pharmaceutical problem solving and methods development is then briefly reviewed. PMID- 8464804 TI - Solid-state diode laser-induced fluorescence detection in high-performance liquid chromatography. AB - The need to measure ultralow levels of pharmaceuticals in biological matrices at femtogram and attogram levels presents a significant challenge to bioanalysts. Liquid chromatography has proven to be a versatile and valuable tool for separating analytes from complex biological matrices and fluorescence detection provides both the sensitivity and the selectivity required to measure femtogram and attogram levels of analytes. Solid-state diode lasers have been used primarily in printers, compact disc recorders, and bar code scanners but have recently been adapted for use as light sources for fluorescence detection. Excellent spectral features in the visible and near-infrared regions of the spectrum, together with low cost and ruggedness, make diode lasers an attractive alternative for use as light sources in analytical measurement. Biological matrices demonstrate minimal background signals in the far-red regions of the spectrum which diode lasers emit and diode lasers are among the most stable light sources available. These facts along with expected developments in labeling systems make the potential for use of diode lasers in LC-detection quite promising. This paper reviews characteristics of diode lasers, the properties of potential visible and near-infrared fluorescent probes, instrumental aspects of diode laser fluorometers, and future trends that can be expected in this exciting field of bioanalytical research. PMID- 8464805 TI - In vivo microdialysis sampling in the bile, blood, and liver of rats to study the disposition of phenol. AB - Methods for continuous in vivo sampling in the bile, blood, and liver extracellular fluid are described. These methods are based on microdialysis sampling in anesthetized rats. A new flow-through microdialysis probe is described for sampling bile while maintaining normal bile flow. All three sites are simultaneously and continuously sampled to provide concentration-time profiles at multiple sites in a single experimental animal. This technique is demonstrated by studying the hepatic metabolism and biliary excretion of phenol in rats. Following an i.v. infusion of phenol, the major hepatic metabolite was found to be phenyl-glucuronide. Hydroquinone and 2-glutathionyl-hydroquinone were also detected but at lower concentrations. A similar pattern of metabolites was found in the bile and blood. For all of the metabolites, bile concentrations are higher than liver concentrations, indicating that the metabolites are actively excreted into the bile. PMID- 8464806 TI - Low-substituted hydroxypropylcellulose as a sustained-drug release matrix base or disintegrant depending on its particle size and loading in formulation. AB - Tablets of acetaminophen as a model drug were prepared with low-substituted hydroxypropylcellulose (L-HPC) of various particle sizes at various loadings in the formulation. Drug release into an aqueous dissolution medium (pH 1.2) was remarkably sustained from tablets prepared with fine L-HPC (LH41) at loadings of more than 20%. Tablets prepared with less than 20% LH41 or with coarse L-HPCs (LH11, LH21, and LH31) disintegrated in the medium, resulting in rapid release of the drug. The difference in behavior could not be explained in terms of differences in tablet strength, but in swelling and water uptake abilities of the tablet's polymer. Swelling work (swelling force), water penetration speed, and water uptake of LH41 (4.4-microns average particle size) were much smaller than those of coarse L-HPCs. The formation of a continuous gel-like layer on the surface of tablets containing more than 20% LH41 was another factor to sustain the drug release rate. PMID- 8464807 TI - Drug release mechanism from a microcrystalline cellulose pellet system. AB - A common form of modified release is the encapsulation of specially formulated or coated pellets. An important first step in the development of a multiparticulate coated dosage form is to characterize the uncoated pellet. In earlier work, an uncoated pellet system developed in these laboratories and prepared from microcrystalline cellulose (MCC) was investigated and found to exhibit both the physical characteristics of an inert matrix and varying degrees of in vitro modified release. The use and characterization of MCC as a spheronization matrix material forms the basis for this formulation study. The drug release mechanism has been verified by varying selected formulation factors and evaluating the resulting pellets according to the relationship developed by T. Higuchi for granular inert matrices. In all cases, this MCC pellet system adhered to the theoretical relationships and the drug release mechanism can, therefore, be classified as an inert matrix. PMID- 8464808 TI - The preparation and characterization of poly(lactide-co-glycolide) microparticles. II. The entrapment of a model protein using a (water-in-oil)-in water emulsion solvent evaporation technique. AB - Poly(lactide-co-glycolide) (PLG) microparticles with entrapped antigens have recently been investigated as controlled-release vaccines. This paper describes the preparation of PLG microparticles with an entrapped model antigen, ovalbumin (OVA), using a (water-in-oil)-in-water emulsion solvent evaporation technique. In a series of experiments, the effects of process parameters on particle size and OVA entrapment were investigated. It was found that smooth, spherical microparticles 1-2 microns in diameter containing up to 10% (w/w) OVA could be produced using a small volume of external aqueous phase containing a high concentration of emulsion stabilizer and a 1:5 antigen:polymer ratio. PAGE analysis, isoelectric focusing, and Western blotting of OVA released from the microparticles in vitro confirmed that the molecular weight and antigenicity of the protein remained largely unaltered by the entrapment procedure. PMID- 8464809 TI - Tissue response to bioerodible, subcutaneous drug implants: a possible determinant of drug absorption kinetics. AB - The fibrous tissue compartments that develop in response to the subcutaneous implantation of bioerodible heat-fused rods of norethindrone and cholesterol (85 and 15%, respectively) were studied by light and electron microscopy at various intervals after implantation to determine whether the biological inflammatory response may play a role in drug absorption. Thirty-five regularly menstruating, sterilized (tubal ligation), healthy females each received four Annuelle rods. The microanatomy of seven of the largest implants (135 mg norethindrone) was studied. A dense fibrous biological compartment was found to surround each rod. By light microscopy no abnormal tissue response was revealed. Scanning and transmission electron microscopy showed that the surfaces of the rods were covered by a cellular matrix of mononuclear cells. The fibrous compartment was composed of a loose cellular bed immediately surrounding the norethindrone rod, a dense fibrous connective tissue envelope containing blood and lymphatic vessels, and an outer fatty connective tissue layer. Transmission electron microscopy confirmed that the cellular tissue immediately surrounding the rods was composed mainly of lipid laden macrophages. Norethindrone levels in tissue capsules at 3 and 10.5 months were 0.05 and 8.4% by weight, respectively. These observations suggest that the local inflammatory response plays a role in the active processing of this delivery system. This picture is qualitatively different from the general view of the fibrous capsule as a simple rate limiting membrane. The effects observed in this study suggest that a more complex, functional biological system develops in response to the subcutaneous introduction of a drug delivery device. PMID- 8464810 TI - Electrochemical characterization of human skin by impedance spectroscopy: the effect of penetration enhancers. AB - The electrochemical properties of human cadaver skin were studied in a diffusion cell with impedance spectroscopy as a function of time in the absence and presence of penetration enhancers dodecyl N,N-dimethylamino acetate and Azone. An improved electrochemical model of skin is presented, and combining the novel model with modern fractal mathematics, the effect of enhancers on the surface of skin is demonstrated. The enhancers appeared to open new penetration routes and increase the ohmic resistance, capacitive properties, and fractal dimension of skin, which means a rougher or more heterogeneous surface. PMID- 8464811 TI - Poly(epsilon-caprolactone) nanocapsules in carteolol ophthalmic delivery. AB - In order to increase the ocular absorption of carteolol, this antiglaucomatous drug was incorporated into either nanoparticles (NP) or nanocapsules (NC). The polymer used was poly(epsilon-caprolactone) (PCL). The dosage forms were tested on intraocular hypertensive-induced rabbits. Results are presented as the chronological variations of the intraocular pressure (IOP) in comparison with the commercial aqueous solution (Carteol eye drops). The therapeutic results (decrease in IOP) were much more pronounced with carteolol incorporated into the colloidal carriers than with the commercial eye drops. Further, NC displayed a better effect than NP because the drug was entrapped in the oily core of the carrier, thus more readily available to the eye. The incorporation of the drug into nanocapsules produced a decline in the cardiovascular side effects in comparison with aqueous eye drops, thus showing that the undesired noncorneal absorption was reduced. In conclusion, colloidal suspension made of poly(epsilon caprolactone) could offer a good opportunity for ophthalmic delivery of drugs. PMID- 8464812 TI - Polyanhydride microspheres that display near-constant release of water-soluble model drug compounds. AB - A new method to prepare polyanhydride microspheres capable of near-constant sustained release of low molecular weight, water-soluble molecules is presented. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. Acid orange 63 (AO), acid red 8 (AR), and p-nitroaniline, were used as model release molecules. P(FAD-SA) microspheres containing the molecules with or without gelatin were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 50-125 microns and encapsulated more than 85% of the molecule, irrespective of the compound used. Near-zero-order degradation kinetics were observed for 5 days as judged by sebacic acid (SA) release. Microsphere degradation was pH sensitive, being enhanced at high pH, and became more stable in acidic conditions, irrespective of the incorporation of gelatin in the matrix. For the gelatin-free microspheres, a close correlation of SA release and AO release was observed (2% loading), suggesting a release mechanism that was controlled dominantly by degradation. However, the incorporation of gelatin into the microsphere significantly extended the periods of molecule release from P(FAD SA) microspheres, although the degradation profile of the microspheres themselves was quite similar to that of gelatin-free microspheres. It is possible that an interaction between FAD monomers and gelatin molecules causes continued release, even after the polymer matrix completely degrades (even after complete degradation, FAD monomers remain because of their poor water solubility). Thermal analysis of polyanhydride microspheres at different degradation stages demonstrated that a crystalline structure was formed between gelatin and the FAD monomers produced with microsphere degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464813 TI - Peptide carrier-mediated transport in intestinal brush border membrane vesicles of rats and rabbits: cephradine uptake and inhibition. AB - The uptake kinetics of cephradine, an amino-beta-lactam antibiotic, were studied in rat and rabbit intestinal brush border membrane vesicles preparations using both the Ca2+ and the Mg2+ methods of preparation, in the presence of an inward proton gradient. The Ca2+ method demonstrated greater uptake of cephradine in intestinal brush border vesicles prepared from both rat and rabbit and was used for these studies. The transport was observed to be of Michaelis-Menten carrier mediated type with a passive transport component. The kinetic parameters obtained were as follows: for rat and rabbit, respectively, Km, 1.6 and 1.9 mM; Jmax', 1.7 and 20.7 nmol/mg/min; Pc' (= Jmax'/Km), 1.1 and 10.9 microL/mg/min; and Pm', 0.4 and 0.8 microL/mg/min. The kinetic parameters for the rat vesicles are consistent with those from our previous perfusion study using a conversion factor of 0.71 cm2/mg protein. The rabbit vesicles exhibited a similar Michaelis constant and a 10-fold larger maximal transport velocity, suggesting a quantitative advantage for the study of carrier-mediated transport in the rabbit compared to rat vesicles from the intestine. Cephradine uptake was inhibited by phenylpropionylproline, a proline derivative, and enalapril, an ACE inhibitor, which do not have an alpha-amino group, as well as dipeptides, tripeptides, and amino-beta-lactam antibiotics in both rat and rabbit vesicles. These results support the suggestion that they share the same peptide carrier pathway for oral absorption and that the vesicles may be a useful tool in developing orally effective peptide-type drugs. PMID- 8464814 TI - An investigation into the mechanical and transport properties of aqueous latex films: a new hypothesis for the film-forming mechanism of aqueous dispersion system. AB - The effects of plasticizer, physical aging, and film-forming temperature on the mechanical and transport properties of films formed from aqueous dispersions of ethylcellulose latex were investigated. The water vapor permeability of latex films was found to decrease with diethyl phthalate to a minimum value and then to increase with diethyl phthalate at higher concentrations. Because of the decrease in free volume and the further coalescence of particles of latex polymer films in the physical aging range, the creep compliance of latex films decreased with physical aging time. Within 60 to 100 degrees C, the film-forming temperature was found to have no effect on the mechanical and transport properties of Aquacoat films. However, since many pinholes formed in the latex films when the film forming temperature was above 100 degrees C, the water vapor permeability of latex films was higher than that of latex films formed between 60 and 100 degrees C. The formation of films from aqueous latex dispersions is suggested to proceed gradually from the top to the bottom of the latex dispersion in this study. PMID- 8464815 TI - Viscoelasticity of anionic polymers and their mucociliary transport on the frog palate. AB - The influence of formulation variables on the rheology of polyanionic formulations and the relationships between viscoelastic properties and mucociliary transport rate were investigated. Polymeric samples were oscillated from 0.001 to 5 Hz using either a "cone and plate" or a "coaxial cylinder" measuring system. The mucociliary transport rates of polymeric samples were determined and compared movement of charcoal powder on the frog palate. For the linear polymeric solutions, sodium carboxymethylcellulose and sodium alginate, the elastic modulus (G') increased with increasing amplitudes during frequency scan. However, the G' or viscous modulus (G'') of partially cross-linked polyacrylic acid (cPAA) samples did not change significantly under oscillation. Both G' and G'' of cPAA samples were significantly influenced by the amount of salt present in the formulation. The rheology of 2% (w/w) cPAA in 90:10 (w/w) propylene glycol:alcohol changed from a viscous fluid to a coarse suspension after neutralization. The pH increased gradually when the nonaqueous formulation reacted with water and the maximum dynamic moduli were obtained after incorporating 20% (w/w) water in the formulation. A negative correlation was found between the G' of linear polyanionic samples and the relative transport rate. However, the lowest mucociliary transport rate was observed when the loss tangent (G''/G') was around 0.4-0.5. PMID- 8464816 TI - Disposition of azole antifungal agents. I. Nonlinearities in ketoconazole clearance and binding in rat liver. AB - The disposition of ketoconazole was characterized in the rat over a wide dose/concentration range. Bolus dose (0.03-10 mg/kg) studies indicate that plasma concentration-time profiles for ketoconazole are not superimposable when dose normalized because of nonlinearities occurring in both volume of distribution and clearance. The volume of distribution decreases from 3 to less than 1 L/kg, while the plasma clearance decreases 10-fold from 25 mL/min/kg as the dose is escalated. From these results, infusion rates were calculated to maintain the plasma concentrations achieved with particular bolus doses. The curvilinear relationship between steady-state plasma concentration (0.015-8.3 mg/L) and ketoconazole infusion rate (0.021-2.45 mg/hr/kg) was analyzed in terms of Michaelis-Menten kinetics. A Vmax of 3.2 mg/hr/kg and Km of 2.1 mg/L were obtained by nonlinear regression analysis. At the end of the ketoconazole infusion, liver, adrenals and kidneys were removed and assayed for ketoconazole. Tissue-to-plasma partition coefficients for the liver and adrenals showed a marked dependence upon steady-state plasma concentration. Both parameters (liver, 22; and adrenals, 53) showed a decrease of approximately 10-fold as the plasma concentrations were increased. In contrast, the kidney:plasma partition coefficient (1.8), blood:plasma concentration ratio (0.6), and plasma binding (96%) of ketoconazole did not show a concentration dependence over the range studied. It is concluded that the liver is an important determinant of ketoconazole's volume of distribution and that saturation of this process accounts largely for the reduction in volume of distribution with increasing dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464817 TI - Interaction of nucleoside analogues with the sodium-nucleoside transport system in brush border membrane vesicles from human kidney. AB - The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na(+)-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na(+)-driven 3H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na(+)-uridine transport was determined. At a concentration of 100 microM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na(+)-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na(+)-uridine uptake with a Ki of 26.4 microM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na(+)-nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The Ki of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside. PMID- 8464818 TI - Pharmacokinetics of a novel antiarrhythmic drug, actisomide. AB - The pharmacokinetics of a novel antiarrhythmic drug, actisomide, were examined in the rat, dog, monkey, and human. The terminal half-life of actisomide was similar (1.15-1.89 hr) across species, regardless of dose. The total plasma clearance was higher in the monkey (13.5-16.4 mL/min/kg) than in the dog (9.01-9.32 mL/min/kg), rat (8.6-9.8 mL/min/kg), or human (6.79 +/- 1.07 mL/min/kg). Excretion of the parent drug was higher in urine than in feces in the dog and rat, whereas in the monkey and human, urinary and fecal excretions of actisomide were similar. In humans, atypical plasma concentration-time curves with double peak concentrations were observed following oral doses. Systemic availability of actisomide was higher in the dog than in the rat, monkey, and human. Further, the systemic availability appeared to increase with dose in the rat and monkey. The species dependent systemic availability appeared to be due primarily to species-dependent absorption of actisomide, and not to species-dependent first-pass metabolism, biliary excretion, and/or renal elimination. The absorption of actisomide in the rat and its in vitro uptake in CaCo-2 cells were pH dependent. The higher systemic availability of actisomide observed in the dog may be due partly to the higher pH in the gastrointestinal (GI) tract of the dog. However, the pH differences in the GI tract of the different species alone did not appear to be enough to explain the difference in systemic availability of actisomide. PMID- 8464819 TI - Comparison of the hepatic uptake clearances of fifteen drugs with a wide range of membrane permeabilities in isolated rat hepatocytes and perfused rat livers. AB - The hepatic uptake clearances of 15 ligands with a wide range of permeabilities were determined in rats using two techniques: centrifugal filtration with isolated hepatocytes and the multiple indicator dilution (MID) method with isolated perfused livers. Some of the uptake clearance values were taken from the literature. Uptake clearance values obtained from isolated hepatocytes were extrapolated to that per gram liver (PSinf.cell), assuming that 1 g of liver has 1.3 x 10(8) cells. The values of PSinf.cell varied from approximately 0.1 to 72 (mL/min/g liver). The values of PSinf.cell were similar to those (PSinf.MID) determined by the MID method for ligands with uptake clearances below approximately 1 mL/min/g liver. However, for the ligands with larger uptake clearances, the PSinf.MID values were lower than the PSinf.cell values and appeared to reach an upper limit (approx. 15-20 mL/min/g liver). The PSinf.cell values of 1-propranolol, tetraphenylphosphonium (TPP+), and diazepam were 72, 43, and 22 mL/min/g liver, respectively, whereas their uptake clearances (PSinf.MID) determined by the MID method were 4 to 10 times lower. One of the possible mechanisms for this discrepancy is that an unstirred water layer, which may exist in Disse's space in isolated perfused livers (and probably under in vivo condition), limits the hepatic uptake rate of ligands with extremely high membrane permeabilities. PMID- 8464820 TI - Rapid determination of methadone in plasma, cerebrospinal fluid, and urine by gas chromatography and its application to routine drug monitoring. AB - Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, cerebrospinal fluid, or urine into n-hexane/isoamyl-alcohol (99/1, v/v). Dextropropoxyphene was used as internal standard. Separation was achieved with a silica SE-52-CB column (13 m x 0.25-mm I.D.). The method was validated for the determination of MET in plasma, urine, and cerebrospinal fluid with a quantification limit of 0.5 ng/mL. The coefficients of variation for within-day and between-day precision were within 10.2 and 14.1%, respectively. Approximately 100 samples can be analyzed by one person in the course of a working day, making the method applicable to routine drug monitoring. The method was demonstrated to be sensitive and accurate for pharmacokinetic studies in plasma, urine, or cerebrospinal fluid. PMID- 8464821 TI - Stabilization of oxygen-sensitive formulations via a secondary oxygen scavenger. AB - The ability to stabilize dopamine hydrochloride formulations via the utilization of a secondary bag containing an antioxidant has been established. By physically separating the drug formulation from the stabilization solution, the chemistry of both solutions can be optimized independently so as to ensure product efficacy. Factors controlling the effectiveness of the proposed stabilization strategy are discussed in the context of actual experimental results. Such a strategy is effective in terms of protecting the formulation during processing/storage only if the product is stored in an oxygen barrier overpouch. PMID- 8464822 TI - Three approaches to the analysis of trace formaldehyde in bulk and dosage from pharmaceuticals. AB - Trace-level determinations for the presence of formaldehyde in both bulk and dosage form pharmaceuticals were developed using three innovative strategies. One system adapted the chromotropic acid spot test for formaldehyde. This was accomplished spectrophotometrically over a linear detection range against authentic control samples. The other two chromatographic approaches necessitated rapid derivatization. One derivative was its corresponding oxime, formaldoxime, which was resolved on a gas chromatographic porous polymer column and sensed by a nitrogen-specific detector. The other derivative, sodium formate, was detected and quantified on an ion chromatograph using an anion-exchange column and a conductivity detector. The chromotropic acid technique was sensitive but not specific for formaldehyde. The chromatographic techniques required a high degree of water solubility. All were subject to interferences that could preclude their use for a particular application. None of the tested samples, which included a penicillin analogue, a pharmaceutical dosage from additive, a vitamin, and biological proteins, showed the presence of formaldehyde at trace levels. PMID- 8464823 TI - Axial ratio measurements for early detection of crystal growth in suspension-type metered dose inhalers. PMID- 8464824 TI - Loading of bovine serum albumin into hydrogels by an electrophoretic process and its potential application to protein drugs. PMID- 8464826 TI - Feasibility of developing a neural network for prediction of human pharmacokinetic parameters from animal data. PMID- 8464825 TI - Molecular cloning of two cDNAs encoding the mouse bilirubin/phenol family of UDP glucuronosyltransferases (mUGTBr/p). PMID- 8464827 TI - Formation of a chromophoric complex between alendronate and copper(II) ions. PMID- 8464828 TI - [Maternal child rearing attitudes, family environment and neurodermatitis in children--a pilot study]. AB - To test hypotheses about pathogen relations in mother-child-dyads with children suffering from eczema, 25 mothers of children with acute eczema, 25 mothers of children with chronic eczema, and 31 mothers of healthy children (average age: 2.4, 2.8, and 1.9 years) were asked to answer a questionnaire concerning educational attitudes (aversive, authoritarian, tenderhearted, overprotective) and family's atmosphere (cooperative, controlled, achievement orientated, dependent). Analyses of variance showed only one significant effect. The results suggest that mothers of children in chronic state are more aversive than mothers of healthy children or mothers of children in acute state. Nevertheless, the mothers' aversion has to be interpreted as a consequence, not at all as an original cause of the disease. Furthermore the mothers' aversion seems to indicate a psychic exhaustion more than an aggressive education. PMID- 8464829 TI - [Separation and divorce counseling in child guidance centers with special reference to criteria of child development]. AB - A socio-ecological concept of counseling in situations of separation and divorce is presented in this article, dividing the process of counseling into specific levels of intervention and phases of divorce. The child's occupation with separation and divorce depends on the level of socio-cognitive development as well as defense and coping strategies. A particular danger of diffusion of roles and of parentifying the child exists in these families. For the long-termed developmental prognosis the degree of cross-linkage and protective factors in the child's environment are vital. The article refers to results of longitudinal studies and research in invulnerability. Furthermore the results of an empirical inquiry at German counseling boards concerning the work with families of divorce are presented. PMID- 8464830 TI - [Anxiety and unconscious fantasies in adoptive families]. AB - First, after a short introduction, the author goes into the threatened identity in adoptive families and the role sexuality hereby plays. This is demonstrated with a case example. Then the unconscious fantasies and dealing with the incest prohibition are described, followed by thoughts about therapy and the problem of the right time to tell the child about his adoption. PMID- 8464831 TI - [Adoption--an irrevocable decision]. PMID- 8464832 TI - Low-dose sulprostone for pregnancy termination in cases of fetal abnormality. AB - Thirty-two pregnancies (11 primi- and 21 multi-gravid) with an abnormal fetus were terminated between 16 and 35 weeks (mean 22 weeks; median 20 weeks) and a continuous intravenous infusion of 1 microgram of the prostaglandin analogue sulprostone. All pregnancies were terminated vaginally, 31 of them with this regimen in a median induction-expulsion interval of 23 h (range 8-52 h). Complete expulsion of the placenta occurred in 72 per cent of cases. Median blood loss was 100 ml (range 20-2000 ml). There were only a few side-effects. We conclude that this induction regimen is both appropriate and safe for pregnancy termination in cases of fetal anomaly. PMID- 8464833 TI - Unusual segregation for 11q;22q parental translocation in a triplet pregnancy: prenatal diagnosis in chorionic villi and amniotic fluid. AB - The prenatal diagnosis of an 11q;22q translocation in a triplet pregnancy detected at the time of chorionic villus sampling (CVS) because of advanced maternal age is reported. Karyotypes obtained from two apparently different CV samples showed the balanced form of translocation, while the one obtained from a third empty sac showed the unbalanced form: 46,XX,-22,+der(22)t(11;22). Second trimester amniocentesis confirmed the balanced translocation in one of the two viable fetuses and a normal karyotype in the other. The detected karyotypes derived from two different types of meiotic segregation, alternate and adjacent 1. To our knowledge, this is the first reported case of an unbalanced karyotype not due to a 3:1 meiotic segregation of this specific translocation. PMID- 8464834 TI - Prenatal diagnosis of Hb H disease due to compound heterozygosity for South-east Asian deletion and Hb constant spring by polymerase chain reaction. AB - A pregnant woman has two children affected by moderately severe Hb H disease due to compound heterozygosity of South-east Asian deletion and Constant Spring mutation. In her third pregnancy, transabdominal chorionic villus sampling was performed at the tenth gestational week to obtain fetal DNA. The polymerase chain reaction was used for detection of both the South-east Asian deletion and the Constant Spring mutation. Hb H disease was diagnosed in the fetus. After genetic counselling, the couple elected to have the pregnancy terminated. PMID- 8464835 TI - Prenatal diagnosis of Zellweger syndrome using DNA analysis. PMID- 8464836 TI - Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4 hydroxybutyric aciduria) PMID- 8464837 TI - Genomic imprinting, human chorionic gonadotropin, and triploidy. PMID- 8464838 TI - Prenatal diagnosis of tetrasomy 12p (Pallister-Killian syndrome) PMID- 8464839 TI - Prenatal diagnosis of trisomy 9 mosaic presenting as a case of Dandy-Walker malformation. AB - Trisomy 9 syndrome is a rare chromosomal anomaly associated with specific patterns of multisystem dysmorphism and occasional central nervous system (CNS) malformations, the most common being the Dandy-Walker malformation. Milder anomalies are usually seen with trisomy 9 mosaicism. We report what we believe to be the first case of a baby with an isolated Dandy-Walker malformation which was diagnosed prenatally and was subsequently found to have a trisomy 9 mosaic syndrome. PMID- 8464840 TI - Prenatal diagnosis of Dandy-Walker malformation in a family displaying X-linked inheritance. AB - The diagnosis of Dandy-Walker malformation was made on the ultrasonographic evaluation of a 33-week male fetus. Pedigree analysis revealed a family history of isolated Dandy-Walker malformation in three other males, suggesting an X linked recessive inheritance pattern. PMID- 8464841 TI - Utilization of beta-carotene from Spirulina platensis by rats. AB - The availability of beta-carotene from Spirulina as compared to standard all trans beta-carotene was studied by the liver and kidney vitamin A storage method. After 21 days of vitamin A depletion, the rats were repleted with beta-carotene from Spirulina and a standard source at two dietary levels (60 and 120 micrograms/day) for a 10 day period. At lower levels, the liver storage levels of vitamin A and the percent of beta-carotene absorption were comparable to those of the standard. At higher levels both these parameters of the Spirulina fed group were significantly (P < 0.01) inferior to the standard source fed group. However, the Spirulina fed group showed better (P < 0.05) growth than the standard fed group did at both low and high levels of feeding. PMID- 8464842 TI - Effect of supplementation of blue green alga (Spirulina) on outcome of pregnancy in rats. AB - To study the supplementary effect of Spirulina, pregnant rats were fed 5 different kinds of diets (casein, Spirulina, wheat gluten, Spirulina + wheat gluten, Spirulina-without additional vitamins and minerals), each providing 22% protein during the period of pregnancy. The outcome of pregnancy was assessed from litter and dams' weight and litter size. Maternal weight gain was found to be maximum with Spirulina + wheat gluten and least with the wheat gluten diet. Rats receiving Spirulina containing diets produced significantly (p < 0.05) higher litter size than those receiving casein and wheat gluten. In spite of having higher litter size, Spirulina containing diet groups produced pups with birth weights comparable to those of casein. Spirulina appears to be a good dietary supplement during pregnancy. PMID- 8464843 TI - Isolation of amaranth flour proteins by fractionation procedures and sonication. AB - The use of whole and defatted amaranth flour for protein isolation of Osborne fractions is described. Extractability of prolamins, the minor fraction, increased from 2.8 to 5% by adding a reducing agent. Glutelins proved to be poorly solubilized (3.3%) in dilute acetic acid, but they reached a high solubility value (40.8%) using a borate buffer in the presence of a reducing agent and a detergent; solubility remarkably declined without the latter two chemicals. Sonication (a fast and simple technique) in the presence of a detergent proved to be more efficient, compared with stirring, for extractability of total unreduced proteins. PMID- 8464844 TI - Available carbohydrates of cereal grains as affected by storage and insect infestation. AB - Total soluble sugar, reducing sugar, non-reducing sugar and starch contents of wheat, maize and sorghum grains were affected adversely at 25, 50 and 75% insect infestation caused by Trogoderma granarium Everts and Rhizopertha dominica Fabricius, separately and mixed population. R. dominica caused significant (P < 0.05) reduction in available carbohydrates at 50 and 75% infestation levels whereas T. granarium achieved similar effect at 75%. Mixture of both insect species caused intermediate losses. Storage of cereal grains up to 4 months resulted in substantial increase in sugars and decrease in starch content, but storage for a shorter period of time did not cause any significant changes in levels of carbohydrates. PMID- 8464845 TI - Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3 week vegetarian diet. AB - The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors. PMID- 8464846 TI - Early effects and the possible mechanism of the effect of Concanavalin A (con A) and Phaseolus vulgaris lectin (PHA-P) on intestinal absorption of calcium and sucrose. AB - Food lectins are known to affect the absorption of nutrients in experimental animals and altered morphology of the intestinal mucosa due to prolonged feeding of lectins is suggested to be the cause. However, toxic symptoms appear in humans immediately after consumption of lectin rich foods and the mechanism of this immediate action is not known. This study reports the immediate effect of Concanavalin A (Con A) and Phaseolus vulgaris lectin (PHA-P) on the absorption of Ca2+ and sucrose in rat intestine and the possible role of lectin-membrane interactions in the process. Calcium absorption was lowered by Con A, and this was observed to be due to Con A interacting with the intestinal mucosal membrane. Similarly, sucrose absorption was also altered, probably due to Con A binding the intestinal mucosal membrane. On the other hand PHA-P did not have any effect on either sucrose or calcium absorption. Results indicate that the effect on intestinal nutrient absorption depends on the type of lectin used (and its concentration) as well as the type of nutrient, besides the duration of exposure of intestinal mucosa to the lectin. PMID- 8464847 TI - Control of enzymatic browning in apple slices by using ascorbic acid under different conditions. AB - Control of phenol oxidase activity in apple slices by the use of ascorbic acid at different pH values, temperature and time of incubation was investigated. The enzyme was almost inactivated at 1% and 1.5% ascorbic acid. Ascorbic acid solution (1%) caused a remarkable inhibition with the increasing acidity up to pH = 1. Heating treatments for apple slices dipped in 1% ascorbic acid caused a reduction of enzymatic browning, optimum temperature for inactivation of the enzyme was between 60-70 degrees C for 15 minutes. Increasing the time of dipping apple slices in 1% ascorbic acid solutions and at different pH values reduce phenolase activity. PMID- 8464848 TI - Effect of sample pretreatments on the storability of ground melon 'egusi' Colocynthis citrillus L. AB - In the maintenance of shelf-stability, nutritional and organoleptic properties of ground melon 'egusi'-Colocynthis citrullus L., vacuum-packaged samples were found to be better than unpackaged samples and samples treated with 0.2% butylated hydroxyanisole (BHA) and 0.02% BHA + 0.045% sodium metabisulphite. After 56 days at 35 degrees C, stored samples showed significant differences (P < or = 0.01) in chemical composition peroxide value (PV), fungal counts and organoleptic attributes. Lipid oxidation and, to a lesser extent, fungal deterioration were responsible for the spoilage of stored ground melon kernel. The dominant fungal flora isolated from stored samples were of the genera Penicillium, Botryodiplodia, Rhizopus and Aspergillus. PMID- 8464849 TI - Niacin, thiamin, and pantothenic acid bioavailability to humans from maize bran as affected by milling and particle size. AB - The objective of the project was to determine the bioavailability of selected B vitamins (niacin, pantothenic acid and thiamin) to humans from wet and dry milled maize brans which were coarsely or finely ground. Using a double cross-over design, the nine subjects were fed laboratory controlled diets containing unsupplemented bread or bread supplemented with finely ground, wet milled maize bran; coarsely ground, wet milled maize bran; finely ground, dry milled corn bran; or coarsely ground, dry milled maize bran. Subjects made complete collections of urine throughout the study which were analyzed for contents of the test vitamins. Although varying somewhat among vitamins, in general, better apparent bioavailability was achieved with the finely ground, dry milled maize bran than with the other test brans. PMID- 8464851 TI - [Tumor necrosis factor alpha in lung diseases]. PMID- 8464850 TI - Tocotrienol and fatty acid composition of barley oil and their effects on lipid metabolism. AB - Barley oil was extracted with hexane from the grain of a high oil waxy hull-less barley. Twelve male broiler chicks were fed corn-based diets with either 10% barley oil, 10% corn oil or 10% margarine ad libitum for ten days. Total plasma cholesterol concentration of the chicks fed barley oil was 34% lower (p < 0.05) than that of the chicks fed margarine. Plasma low density lipoprotein cholesterol concentration of chicks fed barley oil was 53% and 59% lower (p < 0.05) than those of chicks fed corn oil and margarine, respectively. Plasma high density lipoprotein cholesterol and triglyceride concentration of the barley oil group were similar to those of the margarine but higher (p < 0.05) than those of the corn oil group. Chicks fed the barley oil gained more (p < 0.05) body weight than those fed the corn oil and margarine. Barley oil had an effect in suppression of TC and LDLC in chicks compared to margarine. Barley oil suppressed LDLC but not HDLC in chicks compared to corn oil. A greater weight gain of the chicks fed barley oil suggested that these chicks had normally functioning digestion and absorption. alpha-Tocotrienol and gamma-tocotrienol content of the barley oil were 24 and 17 times greater, respectively, than those observed in the corn oil, while the same fractions were not detectable in the margarine. Polyunsaturated fatty acid content of the barley oil was more than threefold that of margarine. These data suggest that alpha-tocotrienol and polyunsaturated fatty acids are hypocholesterolemic components in barley oil. PMID- 8464852 TI - [T4/T8 ratio in bronchoalveolar lavage in sarcoidosis--a marker of activity and/or prognosis?]. AB - In 158 patients with histologically confirmed intrathoracic sarcoidosis the T4/T8 quotient was checked in broncho-alveolar lavage (BAL) for its informative value with regard to activity and prognosis of the disease. In asymptomatic patients with x-ray type I and normal lung function, in radiological remissions of x-ray types I and improvement in the course of disease in patients whose disease had initially been classified acute, we found statistically significantly higher T4/T8 quotients than in the other patient groups; we did not observe any deterioration in the course of the disease. High T4/T8 quotients will thus not generally point to an active or progressing disease; the information conveyed by these data is of limited clinical usefulness in individual cases only. PMID- 8464853 TI - [Benign metastatic leiomyoma of the lung]. AB - The authors report on the case of a woman of 41 years of age presenting with asymptomatic multiple circular foci in the lung that were primarily suspected of being malignomas. Diagnosis of benign metastasising leiomyomas was confirmed for bilateral multiple circular foci suspected of lung metastasising originating from an unknown tumour of the lung. This diagnosis was achieved by open biopsy. The seemingly contradictory diagnosis of a benign but metastasising tumour is characteristic of a rare disease pattern that, however, is well documented in the literature. The course of the disease is compared with the data given in the literature. PMID- 8464854 TI - [Spontaneous pneumothorax as the initial symptom of bronchial cancer]. AB - Spontaneous pneumothorax is caused by benign lung diseases in more than 95 percent. Mainly presenting in younger male patients between 20 and 40 years of age its prognosis is generally good.--On the other hand, pneumothorax as initial manifestation of bronchial carcinoma is a rare complication with poor prognosis. We report such a case of a 70 year-old man, review the literature and describe characteristical problems in diagnosis and therapy of very small bronchogenic tumors. Estimating that only 2 percent of all spontaneous pneumothoraces are coexisted with malignant lung diseases--either primary or secondary--this tumor complication especially must be considered in older patients. Their prognosis may be improved entirely by rapid diagnosis and therapy. PMID- 8464855 TI - [Bronchial hyperreactivity and epidemiology of bronchial asthma in childhood]. AB - Respiratory symptoms are common in childhood with as many as 25% of children aged 7-10 years being troubled by recurrent episodes of cough and wheeze. Subjects with and without asthma differ both in the ease with which airway narrowing is produced by inhalation of nonallergic or nonsensitizing stimuli. A few epidemiologic studies are concerned with the prevalence of bronchial hyperresponsiveness in unselected children. Although increased airway responsiveness is predominantly reported in atopic individuals, even children with no history of atopy or symptoms suggesting asthma produce a bronchial obstruction being challenged by physical exercise, inhalation of cold air or distilled water and pharmacologic stimuli. The relationship between responsiveness to different challenges was investigated in 2 large epidemiological studies on school aged children. The following reports are an informative survey on acceptance, sensitivity, specificity and predictive value of epidemiologic instruments estimating bronchial responsiveness. PMID- 8464856 TI - [Cold air hyperventilation provocation]. AB - The prevalence of asthma was determined by a parental questionnaire in 9403 schoolchildren aged 9-11 years. A cold air challenge was done in 7248 of these children to test for bronchial hyperresponsiveness. Regarding the doctor diagnoses of asthma as reported by the parental questionnaire the specificity of the cold air challenge was 92.5%, the sensitivity 28.7%, the positive predictive value 9.1% and the negative predictive value 98%. PMID- 8464857 TI - [Longitudinal study of bronchial hyperreactivity using the carbachol test with school children]. AB - STUDY DESIGN: Bronchial hyperresponsiveness of 476 schoolchildren (10.8 +/- 2.3 years) was studied three times at 12 months' intervals. The cumulative dose of 400 micrograms carbachol was applied in 50 + 50 + 100 + 200 micrograms steps. A fall of FEV1 of at least 15% was regarded as positive reaction. The test was save, as no severe obstruction was observed, only three children withdrew because of unpleasant cough. RESULTS: Reactivity was observed in 19.1, 10.0, and 5.2% of children at the occasion of the first, second and third test (sensitivity/specificity for prevalence of physician diagnosed asthma: 70/83, 35/91, and 24/96%, respectively). Reactivity was age dependent (7-11 years: 35%, 12-16 years: 18%), not influenced by sex, and the relative risk to be reactive was 1.9 in children 2-3 weeks after a respiratory tract infection. CONCLUSION: For epidemiological purposes carbachol provocation test--like other unspecific bronchial provocation tests--is inappropriate as a single test to classify individuals as asthmatics. PMID- 8464858 TI - [Variability of peak expiratory flow in an unselected sample of school children]. AB - In the framework of an epidemiological study, the information by peak flow variability (PEFV) was compared to the history of asthma in a non-selected population of primary-school children (n = 1812). PEFV as assessed by twice daily recordings of PEF for a one week period (n = 1237) was calculated as average of daily amplitudes (AVAM: average amplitude mean) in the case of at least complete data for five days (n = 991). Elevated PEFV defined as AVAM > 12%, was cross tabulated with the asthma history (self-administered questionnaire). The median (90%-confidence-interval) of AVAM is 6.3% (2.2-15.9%). In 11.2% (n = 111) of the population, AVAM > 12% occurred). The sensitivity of AVAM > 12% with regard to "doctor's diagnosed asthma" (n = 35) is 37%. Under exclusion of children with recurrent wheezy bronchitis a specificity for AVAM > 12% of 90% is found. Our data on primary-school children suggests that PEFV is a specific but only slightly sensitive measurement with regard to previously diagnosed bronchial asthma. PMID- 8464859 TI - [Asthma screening with a standardized running test]. AB - Exercise induced asthma is a common feature of asthma in childhood. We performed a standardized free running test in 1461 primary schoolchildren in first grade (mean age: 7.3 years). A decrease of peak expiratory flow of at least 15% after a 6 minutes exercise period was considered a positive response. For a lifetime prevalence of a physician's diagnosis of asthma the sensitivity of the test was 35.4% and the specificity 94.3%. A positive response was associated with atopy (defined as a positive skin prick test) and with the clinical severity of asthma. PMID- 8464860 TI - [Bronchial hyperreactivity to distilled water]. AB - For an epidemiological study 446 children were challenged with distilled water. The protocol consisted of 10 minutes tidal inhalation of an ultrasonically nebulized aerosol of distilled water. For children presenting with a clinical diagnosis of asthma the odds ratio for a positive challenge test was 9.1 compared to non-asthmatics [95% confidence intervals: 2.4-34.9; p = 0.001]. Symptoms cough (p = 0.03), cough at night (p = 0.03) and atopy defined by prick-test (p = 0.001) were also significantly associated with a positive challenge. The easy conduct of our protocol, the--from a pathophysiological point of view--"close to asthma" stimulus, and the small number of side-effects, indicate that the challenge with distilled water can be regarded as an alternative to metacholine provocation testing. PMID- 8464861 TI - [Bronchoscopic complication]. PMID- 8464862 TI - Bioconversion of chitin to chitosan: purification and characterization of chitin deacetylase from Mucor rouxii. AB - Chitin deacetylase, the enzyme that catalyzes the hydrolysis of acetamido groups of N-acetylglucosamine in chitin, has been purified to homogeneity from mycelial extracts of the fungus Mucor rouxii and further characterized. The enzyme exhibits a low pI (approximately 3). Its apparent molecular mass was determined to be approximately 75 kDa by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and approximately 80 kDa by size-exclusion chromatography, suggesting that the enzyme exists as a monomer. Carbohydrate analysis of purified chitin deacetylase revealed that the enzyme is a high-mannose glycoprotein and that its carbohydrate content is approximately 30% by weight. Chitin deacetylase is active on several chitinous substrates and chitin derivatives. The enzyme requires at least four N-acetylglucosamine residues (chitotetraose) for catalysis, and it is inhibited by carboxylic acids, particularly acetic acid. When glycol chitin (a water-soluble chitin derivative) was used as substrate, the optimum temperature for enzyme activity was determined to be approximately 50 degrees C and the optimum pH was approximately 4.5. PMID- 8464863 TI - Structure-function relationship of human neutrophil collagenase: identification of regions responsible for substrate specificity and general proteinase activity. AB - The family of matrix metalloproteinases is a family of closely related enzymes that play an important role in physiological and pathological processes of matrix degradation. The most distinctive characteristic of interstitial collagenases (fibroblast and neutrophil collagenases) is their ability to cleave interstitial collagens at a single peptide bond; however, the precise region of the enzyme responsible for this substrate specificity remains to be defined. To address this question, we generated truncated mutants of neutrophil collagenase with various deletions in the COOH-terminal domain and chimeric molecules between neutrophil collagenase and stromelysin and assayed the expressed enzymes against type I collagen and the general substrate, casein. Our data suggest that substrate specificity for interstitial collagen is determined by a 16-aa sequence in the COOH-terminal domain of neutrophil collagenase and is influenced by the integrity of a disulfide-defined loop at the COOH terminus for maximal activity. It was found that a relatively large region of 62-aa residues influenced the relative efficiency of collagenolytic activity. In addition to the region that conferred this specificity, a site at the COOH side of the presumptive zinc-binding locus was found to be necessary for general catalytic activity. Mutation of a critical aspartic residue at position 253 within this area resulted in complete loss of proteolytic activity, suggesting that Asp-253 might function as one of the ligands for divalent cations, which are essential for enzymatic activity. PMID- 8464864 TI - Construction and characterization of a bacteriophage T4 DNA polymerase deficient in 3'-->5' exonuclease activity. AB - Bacteriophage T4 DNA polymerase has a proofreading 3'-->5' exonuclease that plays an important role in maintaining the accuracy of DNA replication. We have constructed a T4 DNA polymerase deficient in this exonuclease by converting Asp 219 to Ala. The exonuclease activity of the mutant T4 DNA polymerase has been reduced by a factor of at least 10(7), but it retains a polymerase activity whose kinetic parameters, kcat, Kd DNA, and Kd dATP, are very close to those of the wild-type enzyme. Bacteriophage T4 with the mutant polymerase gene has a markedly increased mutation frequency. Asp-219 in T4 DNA polymerase is within a sequence similar to those surrounding Asp residues previously shown to be essential for the exonuclease activities of the Klenow fragment of Escherichia coli DNA polymerase I (Asp-424), bacteriophage phi 29 DNA polymerase (Asp-66), and Saccharomyces cerevisiae DNA polymerase delta (Asp-405). Thus, these studies support the proposal that there are similar sequences in the active sites for the proofreading exonucleases of these and related DNA polymerases. PMID- 8464865 TI - Hepoxilin A3 is the endogenous lipid mediator opposing hypotonic swelling of intact human platelets. AB - When human blood platelets are exposed to hypotonic medium they swell first but, shortly thereafter, revert toward their original volume in a process termed regulatory volume decrease (RVD). RVD is the result of an enhanced efflux of K+ and Cl- ions and associated water. Platelet RVD is controlled by a short-lived lipoxygenase-derived product (LP). By using a combination of high-performance liquid chromatography, gas chromatography-mass spectrometry, and RVD reconstitution bioassay, we show that LP is identical with hepoxilin A3. In addition we demonstrate that authentic hepoxilin A3 possesses the same biological properties on RVD reconstitution as LP and that the activity of both compounds is amplified through epoxide hydrolase inhibition with 3,3,3-trichloropropene-1,2 oxide. Therefore, we report here that volume expansion causes the formation and release of hepoxilin A3 from intact human platelets and that this hepoxilin plays a major role in volume regulation. PMID- 8464866 TI - Technique for in situ measurement of calcium in intracellular inositol 1,4,5 trisphosphate-sensitive stores using the fluorescent indicator mag-fura-2. AB - Stimulation of cells with calcium-mobilizing agonists frequently results in inositol 1,4,5-trisphosphate (InsP3)-mediated discharge of Ca from an internal store. We report here a technique for directly monitoring Ca within this and other stores in gastric epithelial cells. This technique takes advantage of the propensity of the acetoxymethyl ester derivative of the fluorescent dye mag-fura 2 (which is sensitive to Ca concentrations above 5 microM) to accumulate in subcellular compartments where it can report changes in the free Ca concentration. Intact dye-loaded cells responded to cholinergic stimulation with a decrease in the 350 nm/385 nm excitation ratio, as measured in individual cells with a digital imaging microscope, consistent with reduced Ca concentration in one or more cellular compartments. When cells were permeabilized with digitonin and incubated in an "intracellular buffer," the cytoplasmic dye was released, leaving the mag-fura-2 in the internal store. InsP3 caused the ratio from the trapped indicator to decrease (i.e., Ca was released) in a dose-dependent manner, and this effect was blocked by the InsP3 receptor antagonist heparin. Ca sequestration into the internal store was ATP-dependent, and reuptake into the InsP3-sensitive pool was blocked by thapsigargin, a specific inhibitor of the Ca ATPase of the internal store. We used this technique to investigate the role of Cl on the release and reloading of the InsP3-sensitive internal store and found that Ca uptake was reduced in Cl-free solutions, suggesting an important function for Cl in the refilling of this pool. PMID- 8464867 TI - Neurotrophin 3 supports the survival of developing muscle sensory neurons in culture. AB - Target-dependent cell death of different sub-populations of sensory neurons may be regulated by different trophic factors. To investigate this possibility, we have taken advantage of the fact that the fractions of muscle sensory and cutaneous sensory neurons in chicken dorsal root ganglia (DRG) are probably different at different segmental levels, and we have compared the responses of chicken DRG from levels that do and do not innervate limb tissue to various growth factors in vitro. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) both supported neurite outgrowth from DRG explanted from all segmental levels. In contrast, neurotrophin 3 (NT-3) supported robust neurite growth only from DRG explanted from the cervical or lumbar levels, which innervate limb muscles. Similarly, NGF and BDNF both promoted survival of dissociated neurons from limb and nonlimb segmental levels, whereas NT-3 promoted survival of more neurons from limb compared to nonlimb levels. This suggests that muscle sensory neurons, which are probably more prevalent at the cervical and lumbar levels, may be specifically affected by NT-3. To evaluate this possibility directly, we compared the survival of retrogradely labeled muscle and cutaneous neurons in NGF, BDNF, and NT-3. Identified muscle sensory neurons survived best in vitro in the presence of NT-3, while the survival of identified cutaneous sensory neurons was greatest in NGF. This work provides direct evidence for a potential role of NT-3 versus NGF in the survival of a specific subpopulation of DRG neurons. PMID- 8464868 TI - Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. AB - Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calcium induced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of muCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolytically activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of muCANP in Alzheimer disease, the ratio of the 76-kDa activated isoform of muCANP to its 80-kDa precursor was measured by immunoassay in selected brain regions from 22 individuals with Alzheimer disease and 18 normal controls. This muCANP activation ratio was elevated 3-fold in the prefrontal cortex from patients with Alzheimer disease but not from patients with Huntington disease. The activation ratio was also significantly elevated, but to a lesser degree, in brain regions where Alzheimer pathology is milder and has not led to overt neuronal degeneration. These findings indicate that muCANP activation is not simply a consequence of cellular degeneration but may be associated with dysfunction in many neurons before gross structural changes occur. The known influences of CANPs on cytoskeleton and membrane dynamics imply that persistent CANP activation may contribute to neurofibrillary pathology and abnormal amyloid precursor protein processing prior to causing synapse loss or cell death in the most vulnerable neuronal populations. Pharmacological modulation of the CANP system may merit consideration as a potential therapeutic strategy in Alzheimer disease. PMID- 8464869 TI - Function of yeast cytoplasmic C1-tetrahydrofolate synthase. AB - The protein product of the ADE3 gene of the yeast Saccharomyces cerevisiae has been identified as the cytoplasmic trifunctional C1-tetrahydrofolate (THF) synthase, which possesses 10-formyl-THF synthetase (EC 6.3.4.3), 5,10-methenyl THF cyclohydrolase (EC 3.5.4.9), and 5,10-methylene-THF dehydrogenase (EC 1.5.1.5) activities. However, it has been suggested that the ADE3-encoded C1-THF synthase does not play a role in providing the enzymes involved in the generation of one-carbon intermediates in the biosynthesis of the purine bases but functions in maintaining the structural integrity of the enzyme complex involved in purine biosynthesis [Barlowe, C. K. & Appling, D. A. (1990) Mol. Cell. Biol. 10, 5679 5687]. This hypothesis is based on their finding that the presence of the full length ADE3 C1-THF synthase, whether catalytically active or not, is correlated with the Ade+ phenotype. In contrast to their results, our deletion analysis of the ADE3 gene indicates that the presence of either the synthetase or dehydrogenase/cyclohydrolase domains of C1-THF synthase is enough to complement the adenine requirement in ade3 strains. These results are also consistent with those obtained in heterologous expression of spinach and Clostridium acidiurici monofunctional synthetases in ade3 strains. Heterologous expression studies show that the high synthetase activity may be correlated with the increased growth in medium lacking adenine. These results suggest that the catalytic activity of the C1-THF synthase is involved in purine biosynthesis. PMID- 8464870 TI - Bradyrhizobium japonicum rhizobitoxine genes and putative enzyme functions: expression requires a translational frameshift. AB - Some strains of Bradyrhizobium japonicum produce rhizobitoxine, a phytotoxin that causes foliar chlorosis on susceptible host plants. We have previously obtained Tn5-induced rhizobitoxine null mutants of B. japonicum. DNA sequence analysis of the region surrounding two Tn5 insertions identifies two overlapping open reading frames. The first open reading frame (rtxA) predicts a 54-kDa protein for which the N-terminal 280 residues have sequence similarity to serine: pyruvate aminotransferase. The sequence homology to aminotransferase is consistent with the involvement of this gene in serinol production, a likely intermediate in rhizobitoxine biosynthesis. Previously, a mutant in this open reading frame was shown not to make serinol. The predicted amino acid sequence of the second open reading frame (rtxB) has similarity to yeast O-acetylhomoserine sulfhydrolase. This enzyme function is similar to that required for dihydrorhizobitoxine synthase. The DNA sequence shows that the rtxB open reading frame overlaps rtxA, suggesting that expression of rtxB requires a -1 translational frameshift. Protein expression experiments demonstrate production of an RtxAB fusion protein. The ability of the overlapping rtxA and rtxB sequences to promote a translational frameshift was confirmed in a heterologous expression system. In Escherichia coli, this frameshift appears to be unusually efficient, occurring at a frequency of 80-90%. PMID- 8464871 TI - Role of oxygen vs. glucose in energy metabolism in a mammary carcinoma perfused ex vivo: direct measurement by 31P NMR. AB - The role of glycolysis vs. respiration in tumor energy metabolism has been studied, to date, primarily in vitro by using single cells, multicellular spheroids, or tissue slices. With the advent of in vivo NMR spectroscopy, several investigators have shown that tumor energy status depends on its blood flow. Since manipulation of blood flow alters both oxygen and glucose delivery to a solid tumor, these studies have not been able to separate the relative contribution of oxygen vs. glucose in energy metabolism in vivo. In the present study, we have overcome this problem by combining two methods: the tissue isolated R3230AC mammary adenocarcinoma perfused ex vivo and 31P NMR spectroscopy. The isolated tumor permits one to control the perfusion pressure as well as the metabolite concentrations in the perfusate. NMR spectroscopy permits one to measure the ratio of nucleoside triphosphate to inorganic phosphate (NTP/Pi) and pH. Our results show that (i) the NTP/Pi ratio ex vivo is similar to that observed in vivo prior to surgery, (ii) the NTP/Pi ratio is insensitive to flow changes at high flow rates but is proportional to flow rate at flows comparable to those found in vivo, (iii) the NTP/Pi ratio of these tumors is resistant to hypoxia and is not maintained when glucose is removed or replaced with glutamine, and (iv) although both O2 and glucose are consumed by these tumors, the effect of perfusate flow rate appears to be mediated largely through glucose delivery. The current approach not only provides information about the role of glycolysis vs. respiration in a rodent tumor but also is general and versatile enough to provide similar data in human tumors perfused ex vivo. PMID- 8464872 TI - Expression of truncated forms of liver microsomal P450 cytochromes 2B4 and 2E1 in Escherichia coli: influence of NH2-terminal region on localization in cytosol and membranes. AB - The currently accepted model for the membrane topology of microsomal cytochrome P450 is that of a largely cytoplasmic domain bound by only one or two transmembrane segments at the NH2 terminus. However, as we have reported previously, P450 2E1 lacking the hydrophobic NH2-terminal signal peptide, like the full-length protein, is located in the inner cell membrane when expressed in Escherichia coli and is active with typical substrates. In the present study, additional variants of alcohol-inducible P450 2E1 as well as truncated forms of phenobarbital-inducible P450 2B4 were similarly expressed to determine the influence of the NH2-terminal region on the membrane-binding properties. After deletion of S1 (the NH2-terminal hydrophobic segment), or both S1 and L1 (the following hydrophilic region, expected to be lumenal or cytosolic), one-third of the resulting P450 2B4 (delta 2-20) and 2B4 (delta 2-27) remained membrane bound. Furthermore, the idea that the first two hydrophobic segments are required for attachment by a hairpin loop is not supported by the finding that after deletion of the S1, L1, and S2 segments about half of the P450 2E1 (delta 3-48) remained membrane bound. Since Na2CO3 treatment of the membrane fraction had no significant effect, the findings are apparently not attributable to a loose attachment or occlusion of the truncated proteins. The replacement of neutral amino acids by positively charged residues in positions 3 and 8 of P450 2E1 (delta 3-29) changed the amount in the cytosol from 35% to 50%, and the deletion of residues 2-20 or 2-27 from P450 2B4, which resulted in positive charges occurring in the NH2-terminal region, changed the amount in the cytosol from 27% to 67%. We conclude that alterations in the NH2-terminal region can change the location of the cytochrome from largely membranous to largely cytosolic and that the first two hydrophobic segments are not uniquely involved in membrane attachment. PMID- 8464873 TI - Cholesterol deprivation affects the fluorescence properties of a ceramide analog at the Golgi apparatus of living cells. AB - Previous studies have established that a fluorescent analog of ceramide, N-[7-(4 nitrobenzo-2-oxa-1,3-diazole)] -6-aminohexanoyl-D-erythro-sphingosine (C6-NBD Cer), is a vital stain for the Golgi apparatus and a useful tool for studying the sorting and transport of sphingolipids along the secretory pathway in animal cells. Here, we examine the effects of various culture conditions on labeling of the Golgi apparatus of human skin fibroblasts by C6-NBD-Cer and demonstrate that cholesterol deprivation affects the fluorescence properties of the probe at this organelle. Labeling of the Golgi apparatus by C6-NBD-Cer was dramatically reduced in cells grown in medium containing lipoprotein-deficient serum compared to cells grown in medium containing normal serum. Quantitative fluorescence microscopy showed that this apparent reduction in labeling resulted from accelerated photo bleaching of the fluorescent analog. C6-NBD-Cer labeling of the Golgi apparatus was restored in cholesterol-deprived cells by stimulating endogenous cholesterol biosynthesis with mevalonic acid or by adding exogenous nonlipoprotein cholesterol or low density lipoprotein to the culture medium. In addition, when cells grown in medium containing normal serum were perforated and treated with cholesterol oxidase, an apparent reduction in labeling resulted, further implicating an intracellular pool of cholesterol in the potentiation of C6-NBD Cer fluorescence. These results demonstrate that cytological studies using C6-NBD Cer are affected by cholesterol deprivation and suggest that this fluorescent lipid may be used to monitor cholesterol at the Golgi apparatus of living cells. PMID- 8464874 TI - Effect of T-cell receptor antagonism on interaction between T cells and antigen presenting cells and on T-cell signaling events. AB - T-cell receptor (TCR) antagonism induced by complexes of antigen analogue with major histocompatibility complex (MHC) molecules results in efficient inhibition of antigen-dependent T-cell responses. We have investigated some of the possible mechanisms by which TCR antagonists bound to the MHC molecules of antigen presenting cells (APCs) can inhibit T-cell activation. Using a nonstimulatory analogue of the antigenic peptide influenza hemagglutinin-(307-319), we showed that MHC/antagonist complexes completely inhibit very early intracellular events of antigen-dependent T-cell activation, such as inositol phosphate turnover and Ca2+ influx. In a parallel series of experiments, the effect of TCR antagonist peptide on membrane-related activation events was also investigated. It was found that MHC/antagonist complexes on the surface of APCs did not induce stable conjugates with T cells and, most interestingly, did not inhibit antigen-induced conjugate formation. Thus, our data suggest that antagonistic peptides do not interfere with the cellular events that are required for stable T-cell/APC conjugate formation but do inhibit early biochemical events required for T-cell proliferation. The data are discussed with respect to the role of surface receptor clustering in TCR antagonism. PMID- 8464875 TI - Recognition of vaccinia virus-encoded major histocompatibility complex class I antigens by virus immune cytotoxic T cells is independent of the polymorphism of the peptide transporters. AB - In the cytotoxic T-cell response to viruses, peptide antigens of cytoplasmic origin are presented at the cell surface by the highly polymorphic major histocompatibility complex (MHC) class I molecules to CD8+ T-lymphocyte receptors. Peptide transporter molecules and other MHC-linked gene products have been implicated in the generation and import of antigenic peptides into the lumen of the endoplasmic reticulum for assembly with MHC class I glycoproteins. These accessory molecules in the antigen-presentation pathway map to a polymorphic region in the class II MHC, and the possibility of their allele-specific selectivity in antigen presentation has been raised. Here we show that additional, functionally polymorphic components are not apparent in an in vitro mouse MHC class I-restricted cytotoxic T-cell response to vaccinia and influenza viruses. When the mouse H-2Kd molecule was expressed via a recombinant vaccinia virus in target cells of different mouse MHC haplotypes or cells of rat, Syrian hamster, monkey, and human origin, efficient Kd-restricted and vaccinia virus specific lysis was observed as measured with bulk effectors and at the clonal level. In addition, human transporters efficiently processed peptides originating from influenza virus nucleoprotein and hemagglutinin antigens as recognized by mouse influenza immune cytotoxic T cells. PMID- 8464876 TI - p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene. AB - The p70 (Ku) autoantigen has been described as a nonhistone nuclear protein recognized by antibodies from lupus patients. In our studies on the regulation of T-cell receptor (TCR) beta-chain gene expression we have identified the p70 lupus autoantigen as a DNA-binding protein that binds the enhancer of the TCR beta chain gene. This enhancer is essential for expression of the TCR beta gene. The core TCR beta enhancer contains the E3 motif, which we show here is essential for enhancer activity. The protection of the E3 motif in T cells and the marked reduction in enhancer activity when the E3 motif is mutated underline its physiological importance in regulating beta enhancer activity. The p70 lupus autoantigen gene was identified by screening T-cell lambda gt11 libraries with an E3 probe. The gene encodes a protein which binds the E3 motif in a sequence specific manner. The identification of a 70-kDa protein as a major E3-binding protein by UV crosslinking is consistent with the conclusion that the p70 lupus autoantigen binds the beta enhancer. Finally, we have shown that T-cell nuclear proteins which bind the E3 motif bear p70 (Ku) lupus autoantigenic determinants. Together these data suggest that the p70 autoantigen binds a critical motif in the beta enhancer and probably regulates TCR beta gene expression. PMID- 8464877 TI - Blockade of human immunodeficiency virus type 1 production in CD4+ T cells by an intracellular CD4 expressed under control of the viral long terminal repeat. AB - A retroviral vector was constructed in which a gene encoding a mutated soluble CD4 protein that is retained in the endoplasmic reticulum (sCD4-KDEL) is expressed under control of human immunodeficiency virus type 1 (HIV-1) regulatory elements. HIV-1 infection of a human T-cell line transduced with this vector led to induction of sCD4-KDEL synthesis and a block in transport of the HIV envelope protein to the cell surface. There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation. Infected cells gradually disappeared from the culture over a period of 2 months. This intracellular trap for HIV has potential application in gene therapy for AIDS. PMID- 8464878 TI - Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor. AB - The gastrointestinal tract plays a major role in the pathogenesis and pathophysiology of infection by the type 1 human immunodeficiency virus (HIV-1). It is a potential route for viral entry and it is the site of a number of complications, including both opportunistic infections and a primary HIV-induced enteropathy. Correspondingly, both in vivo and in vitro studies have demonstrated HIV infection of gastrointestinal cells of lymphoid and epithelial origin. HT-29, a human colonic epithelial cell line that is infectable with many HIV-1 strains, does not express CD4 protein or mRNA. Recent studies showed that antibodies recognizing a neutral glycolipid related to galactosylceramide (GalCer) in HT-29 cells inhibited HIV-1 infection of this cell line, extending previous findings in neural cells. In the current studies, we further analyzed the neutral glycolipids of HT-29 cells and showed that they contained authentic GalCer and that recombinant gp120 bound to this glycolipid. Moreover, by analyzing GalCer expression in clones derived from HT-29 and Caco-2 (another human colonic cell line), we observed that the level of expression of this glycolipid was associated with the sensitivity to HIV-1 infection. Subclones of Caco-2 did not express GalCer and were not infectable with any of three HIV-1 strains. These results strengthen the possibility that GalCer is an alternative receptor in CD4- cell lines. Furthermore, since GalCer is a major glycolipid in epithelial cells of the small intestine and colon, these results provide a structural basis for the binding of HIV-1 by gastrointestinal epithelial cells and the entry of the virus into those cells. PMID- 8464879 TI - Learning selectively increases protein kinase C substrate phosphorylation in specific regions of the chick brain. AB - The effect of imprinting, an early form of exposure learning, on the phosphorylation state of the protein kinase C substrates myristoylated alanine rich C-kinase substrate (MARCKS) and protein F1/43-kDa growth-associated protein (F1/GAP-43) was studied in two regions of the chick forebrain. One region, the intermediate and medial part of the hyperstriatum ventrale (IMHV), is probably a site of long-term memory; the other, the wulst, contains somatic sensory and visual projection areas. After imprinting, a significant increase in MARCKS protein phosphorylation was observed in the left IMHV but not the right IMHV. No significant alteration in F1/GAP-43 was observed in IMHV. MARCKS was resolved into two acidic components of pI approximately 5.0 and approximately 4.0. Phosphorylation of the pI approximately 5.0 MARCKS but not the pI approximately 4.0 MARCKS was significantly altered by imprinting. The partial correlation between preference score (an index of learning) and phosphorylation, holding constant the effect of approach activity during training, was significant only for the pI approximately 5.0 MARCKS in the left IMHV. A significant negative partial correlation between preference score and F1/GAP-43 phosphorylation in the right wulst was observed. Because the imprinting-induced alteration in MARCKS is selective with respect to phosphoprotein moiety, hemispheric location, and brain region, we propose that these alterations may be central to the learning process. PMID- 8464880 TI - Adenine nucleoside diphosphates block adaptation of mechanoelectrical transduction in hair cells. AB - By adapting to sustained stimuli, hair cells in the internal ear retain their sensitivity to minute transient displacements. Because one model for adaptation asserts that this process is mediated by a myosin isozyme, we reasoned that we should be able to arrest adaptation by interfering with myosin's ATPase cycle though introduction of ADP into hair cells. During tight-seal, whole-cell recordings of transduction currents in cells isolated from bullfrog (Rana catesbeiana) sacculus, dialysis with 5-25 mM ADP gave variable results. In half of the cells examined, the rate of adaptation remained unchanged or even increased; adaptation was blocked in the remaining cells. Because we suspected that the variable effect of ADP resulted from the conversion of ADP to ATP by adenylate kinase, we employed the ADP analog adenosine 5'-[beta-thio]diphosphate (ADP[beta S]), which is not a substrate for adenylate kinase. Adaptation consistently disappeared in the presence of 1-10 mM ADP[beta S]; in addition, the transduction channels' open probability at rest grew from approximately 0.1 to 0.8 or more. Both effects could be reversed by 2 mM ATP. When used in conjunction with the adenylate kinase inhibitor P1,P5-bis(5'-adenosyl) pentaphosphate (Ap5A), ADP had effects similar to those of ADP[beta S]. These results suggest that adaptation by hair cells involves adenine nucleotides, and they lend support to the hypothesis that the adaptation process is powered by a myosin motor. PMID- 8464881 TI - Cocatalytic zinc motifs in enzyme catalysis. AB - Cocatalytic zinc binding sites are characteristic of enzyme molecules which contain two or more zinc and/or other metal atoms. In each site an aspartate, glutamate, or histidine residue simultaneously binds to two zinc atoms or a zinc and a different metal atom. In the resultant amino acid bridge, two of the cocatalytic metal atoms bind to the same amino acid. Consequently the participating metal atoms are in close proximity and function as a catalytic unit, typical of this motif. In these functional units aspartate seems to be preferred over glutamate. Serine, threonine, tryptophan, and lysine residues are encountered as zinc ligands, although they have not so far been identified as ligands in monozinc enzymes or DNA-binding zinc proteins. The resultant coordination spheres and their mechanistic implications raise interesting questions for further study. PMID- 8464882 TI - Vimentin mRNA location changes during muscle development. AB - The mRNAs for some cytoskeletal proteins are localized, suggesting that mRNA for these proteins may concentrate at sites appropriate for assembly. To test this hypothesis, we observed vimentin mRNA in developing chicken muscle cultures by in situ hybridization with a digoxigenin-labeled DNA probe to vimentin, detected by confocal microscopy using fluorescent anti-digoxigenin antibody. This method has submicrometer resolution. In developing muscle, vimentin mRNA was bipolar in young myoblasts, somewhat perinuclear in elongated myoblasts and spread fibroblasts, and diffuse in young and developing myotubes. In mature myotubes, vimentin mRNA occurred at costameres with vimentin protein. Localization of mRNA may prove important for assembling and maintaining differentiated cytoskeletal structures, as it is for organizing the embryo. PMID- 8464883 TI - A dominant-negative mutant of Max that inhibits sequence-specific DNA binding by Myc proteins. AB - Myc proteins are basic helix-loop-helix/leucine-zipper proteins that bind to specific DNA sequences. In vivo, Myc proteins have been found associated with Max, another basic helix-loop-helix/leucine-zipper protein. However, it is not known to what extent the dimerization of Myc with Max is required for the manifestation of the Myc-induced phenotype. To investigate this, we constructed a dominant-negative mutant of Max, named dMax, that inhibits sequence-specific DNA binding of Myc proteins. Using a rat neuroblastoma model system, we show that dMax reverts N-Myc-induced changes in cellular gene expression. A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression. These data support the hypothesis that N-Myc affects neuroblastoma gene expression through the formation of a DNA-binding heterodimeric complex with Max in vivo. PMID- 8464884 TI - Primary structure and functional expression of a cDNA encoding the thiazide sensitive, electroneutral sodium-chloride cotransporter. AB - Electroneutral Na+:Cl- cotransport systems are involved in a number of important physiological processes including salt absorption and secretion by epithelia and cell volume regulation. One group of Na+:Cl- cotransporters is specifically inhibited by the benzothiadiazine (thiazide) class of diuretic agents and can be distinguished from Na+:K+:2Cl- cotransporters based on a lack of K+ requirement and insensitivity to sulfamoylbenzoic acid diruetics like bumetanide. We report here the isolation of a cDNA encoding a thiazide-sensitive, electroneutral sodium chloride cotransporter from the winter flounder urinary bladder using an expression cloning strategy. The pharmacological and kinetic characteristics of the cloned cotransporter are consistent with the properties of native thiazide sensitive sodium-chloride cotransporters in teleost urinary bladder and mammalian renal distal tubule epithelia. The nucleotide sequence predicts a protein of 1023 amino acids (112 kDa) with 12 putative membrane-spanning regions, which is not related to other previously cloned sodium or chloride transporters. Northern hybridization shows two different gene products: a 3.7-kb mRNA localized only to the urinary bladder and a 3.0-kb mRNA present in several non-bladder/kidney tissues. PMID- 8464885 TI - Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis. AB - Biological nitrogen fixation is catalyzed by nitrogenase, a complex metalloenzyme composed of two separately purifiable component proteins encoded by the structural genes nifH, nifD, and nifK. Deletion of the Azotobacter vinelandii nifS gene lowers the activities of both nitrogenase component proteins. Because both nitrogenase component proteins have metallocluster prosthetic groups that are composed of iron- and sulfur-containing cores, this result indicated that the nifS gene product could be involved in the mobilization of the iron or sulfur required for metallocluster formation. In the present work, it is shown that NIFS is a pyridoxal phosphate-containing homodimer that catalyzes the formation of L alanine and elemental sulfur by using L-cysteine as substrate. NIFS activity is extremely sensitive to thiol-specific alkylating reagents, which indicates the participation of a cysteinyl thiolate at the active site. Based on these results we propose that an enzyme-bound cysteinyl persulfide that requires the release of the sulfur from the substrate L-cysteine for its formation ultimately provides the inorganic sulfide required for nitrogenase metallocluster formation. The recent discovery of nifS-like genes in non-nitrogen-fixing organisms also raises the possibility that the reaction catalyzed by NIFS represents a universal mechanism that involves pyridoxal phosphate chemistry, in the mobilization of the sulfur required for metallocluster formation. PMID- 8464886 TI - Alteration of the cleavage distance of Fok I restriction endonuclease by insertion mutagenesis. AB - Fok I restriction endonuclease recognizes the nonpalindromic pentadeoxyribonucleotide 5'-GGATG-3'.5'-CATCC-3' in duplex DNA and cleaves 9 and 13 nucleotides away from the recognition site. Recently, we reported the presence of two distinct and separable protein domains within this enzyme--one for the sequence-specific recognition and the other for endonuclease activity. Here, we report the construction of two insertion mutants of Fok I endonuclease. The mutant enzymes were purified, and their cleavage properties were characterized. The mutants have the same DNA sequence specificity as the wild-type enzyme. However, compared with the wild-type enzyme, they cleave one nucleotide further away from the recognition site on both strands of the DNA substrates. Thus, it is possible to alter the cleavage distance of Fok I by protein engineering. PMID- 8464887 TI - The envelope glycoprotein of human immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes. AB - Mononuclear phagocytes infected with human immunodeficiency virus 1 (HIV-1) produce soluble factors that kill neurons in culture. To define the molecular events that lead to neuron killing, HIV-1 proteins were tested for the ability to trigger release of neurotoxins from human monocytes and lymphocytes. None of the recombinant-derived HIV-1 proteins examined (reverse transcriptase, protease, gag, nef, or gp120) were directly neurotoxic at concentrations from 100 pM to 10 nM. The envelope glycoprotein gp120 did, however, stimulate both isolated human blood monocytes and the monocytoid line THP-1 (but not lymphocytes or the lymphoid cell line H9) to discharge neurotoxic factors. These toxins consisted of heat-stable, protease-resistant molecules (< 500 Da) that copurified with neurotoxins from HIV-1-infected THP-1 cells and were blocked by antagonists to N methyl-D-aspartate receptors. Release of neurotoxins through gp120 stimulation involved monocytoid CD4 receptors because toxin production could be inhibited either by a monoclonal antibody to the CD4-binding region of gp120 or by soluble CD4 receptors. Alternatively, production of neuron-killing factors could be induced with a peptide from the CD4-binding region of gp120. These data show that the HIV-1 envelope glycoprotein alone can stimulate neurotoxin release by binding to CD4 receptors of mononuclear phagocytes. Such neurotoxic factors may, in turn, contribute to the central nervous system dysfunction associated with HIV-1 by acting on neurons through N-methyl-D-aspartate receptors. PMID- 8464888 TI - Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon gamma. AB - Interleukin (IL)-2, IL-4, IL-7, tumor necrosis factor (TNF), or interferon-gamma (IFN-gamma) has been shown to be able to induce tumor rejection if produced locally by the tumor cells after gene transfer. To analyze whether the cellular rejection mechanisms are different or redundant we have expressed the cytokines in the same tumor cell line (J558L). Cell depletion experiments revealed that all cytokines required CD8+ T cells for complete long-term tumor eradication, although effective but transient host-dependent tumor suppression was also observed in the complete absence of CD8+ T cells. The transient tumor suppression induced by IL-2, IL-4, TNF, or IFN-gamma was also operative in nude and severe combined immunodeficient mice, whereas only tumor suppression induced by IL-7 was dependent on the presence of CD4+ T cells and was not evident in nude mice. The T cell-independent effector arm of IL-2 and IFN-gamma but not IL-4 and TNF was mediated in part by natural killer cells. The transience of tumor suppression in the absence of T cells reflected loss of cytokine production in the case of TNF, IL-2, and IL-4 but not IFN-gamma. Immunohistologic analysis revealed all cytokine producing tumors to be heavily infiltrated by macrophages. IL-4 and IL-7 tumors additionally contained eosinophils. The infiltration by T cells did not necessarily reflect their contribution to tumor rejection. Thus, the different cytokines activate heterogeneous transient tumor-suppressive mechanisms but always require CD8+ T cells for complete tumor rejection. PMID- 8464889 TI - Class II-positive hematopoietic cells cannot mediate positive selection of CD4+ T lymphocytes in class II-deficient mice. AB - Generation of immunocompetent alpha/beta T-cell receptor-positive T cells from CD4+CD8+ thymocytes depends upon their interaction with thymic major histocompatibility complex (MHC) molecules. This process of positive selection provides mature T cells that can recognize antigens in the context of self-MHC proteins. Previous studies investigating haplotype restriction in thymic and bone marrow chimeras concluded that radioresistant thymic cortical epithelium directs the positive selection of thymocytes. There is controversy, however, as to whether intra- or extrathymic radiosensitive bone marrow-derived macrophage and dendritic cells also can mediate positive selection. To determine whether CD4+ T cells can be positively selected by hematopoietic cells, we generated chimeric animals expressing MHC class II molecules on either bone marrow-derived or thymic stromal cells by using a recently produced strain of MHC class II-deficient mice. CD4+ T cells developed only when class II MHC molecules were expressed on radioresistant thymic cells. In contrast to what recently has been observed for the selection of CD8+ T lymphocytes, MHC class II-positive bone marrow-derived cells were unable to mediate the selection of CD4+ T cells when the thymic epithelium lacked MHC class II expression. These data suggest that CD4+ and CD8+ T cells may be generated by overlapping, but not identical, mechanisms. PMID- 8464890 TI - HMT, encoded by H-2M3, is a neoclassical major histocompatibility class I antigen. AB - H-2M3 encodes HMT, the major histocompatibility complex (MHC) class I heavy chain of the maternally transmitted antigen (Mta). Like classical MHC class I genes, the expression of M3 can be stimulated by gamma-interferon and its message can be detected from mid-gestational embryos (day 8) through adulthood. HMTb, a nonimmunogenic allelic form of HMT, differs from the common HMTa molecule by four amino acids, of which only two (residues 31 and 95) are located in the alpha 1 and alpha 2 domains that form the peptide-binding groove. Recognition of site directed mutants by Mta-specific cytotoxic T lymphocytes was hardly affected by the substitution of Met for Val31 but was abolished by the substitution of Gln for Leu95, which is located in the beta-sheet floor of the peptide-binding groove. Thus a single amino acid difference is responsible for the immunological silence of HMTb. PMID- 8464891 TI - Bone lead content assessed by L-line x-ray fluorescence in lead-exposed and non lead-exposed suburban populations in the United States. AB - Measurements of lead (Pb) in bone reflect cumulative Pb exposure, whereas blood Pb levels are indices of absorption during the previous 21-30 days. This study was undertaken to estimate bone Pb concentrations by L-line x-ray fluorescence (LXRF) in a United States suburban population which was exposed to unusually high levels of Pb in emissions from an adjacent factory during 1963-1981, compared with concentrations similarly estimated in a matched suburban community without unusual Pb exposure. The mean bone Pb value in 269 residents of the highly exposed suburb (15 ppm) was 3-fold greater than that of the reference suburb (5 ppm). LXRF estimates of bone Pb identified those individuals at risk for adverse effects of Pb, whereas blood Pb levels were uninformative. Average LXRF-estimated bone Pb concentrations in residents of the unusually exposed suburb approximated estimated values in workers at Pb-processing factories. PMID- 8464892 TI - Attempts to restore scrapie prion infectivity after exposure to protein denaturants. AB - A wealth of experimental evidence argues that infectious prions are composed largely, if not entirely, of the scrapie isoform of the prion protein. We attempted to restore scrapie infectivity after exposure to protein denaturants including urea, chaotropic salts, and SDS. None of the procedures restored infectivity. Dialysis to remove slowly chaotropic ions and urea failed to restore scrapie infectivity. Attempts to create monomers of the scrapie isoform of the prion protein under nondenaturing conditions using a wide variety of detergents have been unsuccessful, to date, except for one report claiming that scrapie infectivity could be recovered from 12% polyacrylamide gels after SDS/PAGE [Brown, P., Liberski, P. P., Wolff, A. & Gajdusek, D. C. (1990) Proc. Natl. Acad. Sci. USA 87, 7240-7244]. We found that < 0.001% of the infectious prion titer could be recovered from the region of a polyacrylamide gel where the denatured proteinase K-resistant core of the scrapie isoform of the prion protein and other 30-kDa proteins migrate. We conclude that under the denaturing conditions used for SDS/PAGE, the scrapie isoform of the prion protein is denatured and little or no renaturation occurs upon injection of fractions eluted from gels into animals for bioassays. PMID- 8464893 TI - Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice. AB - We have explored the use of adenovirus-mediated gene transfer to transiently elicit production of low density lipoprotein (LDL) receptors in mice. A recombinant adenovirus carrying the human LDL receptor cDNA restored LDL receptor function in receptor-deficient cultured cells. Intravenous injection of recombinant virus acutely lowered plasma cholesterol levels and increased the rate of 125I-labeled LDL clearance from the circulation in normal mice. At 4 days after virus injection, the t1/2 of plasma LDL was reduced up to 10-fold. An estimated 90% of the parenchymal cells in liver expressed the adenovirus transferred genes as judged by immunofluorescence of LDL receptors or by beta galactosidase staining. These results demonstrate that adenovirus-mediated transfer of the LDL receptor gene provides an efficient way of augmenting LDL receptor gene function in the liver over the short term. PMID- 8464894 TI - Mutation of p53 in primary biopsy material and cell lines from Hodgkin disease. AB - The p53 tumor-suppressor gene encodes a nuclear phosphoprotein that arrests cell cycle progress at G1. It may facilitate DNA damage repair and is frequently mutated in many human tumors. Hodgkin disease, a malignant condition of the lymphoid system, is characterized by the presence of Reed-Sternberg cells and mononuclear variants (Hodgkin cells), whose etiology remains unknown. The large multinucleated Reed-Sternberg cells often comprise < 1% of the total cell population within a biopsy specimen and are thought to be the neoplastic component in an admixture of reactive cells. It has been shown in the large majority of cases that up to 60% of these multinucleated cells react with CM-1, an anti-p53 antibody. However, whether this "overexpression" of p53 protein reflects abnormality at the DNA level can no longer be assumed by immunocytochemistry alone. p53 from six Hodgkin disease-derived cell lines was examined by immunoprecipitation, polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis, and sequencing. In one cell line, point mutations were identified in exons 5 and 8 of p53. Sequencing of cloned PCR products confirmed the mutations to be on different alleles. A strategy involving extraction of nuclei followed by enrichment by flow cytometry was used to determine whether p53 overexpression in the Reed-Sternberg cells from patient biopsy material was due to mutations in this gene. Single-strand conformation polymorphism revealed additional bands in the polyploid nuclear preparations, suggesting abnormalities, and sequence analysis confirmed the presence of point mutations. PMID- 8464895 TI - Kedarcidin chromophore: an enediyne that cleaves DNA in a sequence-specific manner. AB - Kedarcidin chromophore is a 9-membered enediyne, recently isolated from an actinomycete strain. In vivo studies show this molecule to be extremely active against P388 leukemia and B16 melanoma. Cytotoxicity assays on the HCT116 colon carcinoma cell line result in an IC50 value of 1 nM. In vitro experiments with phi X174, pM2 DNA, and 32P-end-labeled restriction fragments demonstrate that this chromophore binds and cleaves duplex DNA with a remarkable sequence selectivity producing single-strand breaks. The cleavage chemistry requires reducing agents and oxygen similar to the other naturally occurring enediynes. Certain cations (Ca2+ and Mg2+) prevent strand cleavage. High-resolution 1H NMR studies on the chromophore in the presence of calcium chloride implicate the 2 hydroxynaphthoyl moiety in DNA binding. Interestingly, the kedarcidin chromophore appears structurally related to neocarzinostatin yet recognizes specific DNA sequences in a manner similar to calicheamicin gamma 1I, an enediyne with a significantly different structure. Moreover, kedarcidin and calicheamicin share a DNA preferred site, the TCCTN-mer. These observations indicate that the individual structural features of these agents are not solely responsible for their DNA selectivity. Rather, a complementarity between their overall tertiary structure and the local conformation of the DNA at the binding sites must play a significant role in the recognition process. PMID- 8464896 TI - Progression toward tumor cell phenotype is enhanced by overexpression of a mutant p53 tumor-suppressor gene isolated from nasopharyngeal carcinoma. AB - We recently reported the detection of a heterozygous G-->C point mutation at codon 280 of p53 in nasopharyngeal carcinoma, which causes an Arg-->Thr substitution. To test whether this mutant p53 has gained function as an oncogene, we overexpressed the mutant p53 in nontumorigenic cells of two model systems: (i) human Saos-2 cells lacking endogenous p53 and (ii) mouse JB6 variants that bear endogenous wild-type p53. Although they have no growth advantage over the neomycin controls in monolayer culture, human Saos-2 transfectants overexpressing mutant p53 do show enhanced progression to tumor cell phenotype, as assayed by anchorage-independent growth and in vivo tumorigenicity. The enhancement is seen only in transfectants expressing higher levels of p53 protein. In the mouse JB6 system, the mutant p53 functions dominantly in the presence of endogenous wild type p53 to enhance progression of preneoplastic promotion-sensitive cells toward anchorage-independent phenotype. Mouse JB6 transfectants of mutant p53 are, however, not tumorigenic in nude mice. We conclude from these studies that the G- >C point mutation of p53 at codon 280 is a gain-of-function mutation that appears to operate dominantly and that the mutant p53-thr280 has only moderate oncogenic activity. This mutation may cooperate with other yet-to-be isolated genes in the genesis of nasopharyngeal carcinoma. PMID- 8464897 TI - Highly lytic CD8+, alpha beta T-cell receptor cytotoxic T cells with major histocompatibility complex (MHC) class I antigen-directed cytotoxicity in beta 2 microglobulin, MHC class I-deficient mice. AB - Targeted disruption of the beta 2-microglobulin (beta 2m) gene results in major histocompatibility complex (MHC) class I deficiency and virtual disappearance of functional CD8+ cytotoxic T lymphocytes (CTLs) in beta 2m-deficient (beta 2m-/-) mice. We asked whether the beta 2m-/- mice are able to reject tumor cells injected i.p. and what is the cellular composition of peritoneal exudate leukocytes (PELs) from such mice. We found that beta 2m-/- mice do reject MHC class I-bearing tumor cells injected i.p. Surprisingly, analysis of PEL CTLs obtained from i.p. tumor-injected beta 2m -/- mice revealed the presence of a large proportion of functional, tumor-destroying CD8+, CD4-, alpha beta T-cell receptor-positive, CD3+, Thy-1+, MHC class I-negative CTLs with strong MHC class I-directed cytotoxic activity. These results call for careful studies of local accumulation of CD8+ CTLs in beta 2m -/- mouse models and suggest that the dramatic decrease in MHC class I expression caused by beta 2m gene disruption does not prevent CD8+/CD4- cell selection and expansion. PMID- 8464898 TI - Tissue typing the HLA-A locus from genomic DNA by sequence-specific PCR: comparison of HLA genotype and surface expression on colorectal tumor cell lines. AB - A system devised for tissue typing the HLA-A locus by PCR from genomic DNA has been used to investigate abnormalities of HLA expression in a panel of 30 colorectal tumor cell lines, by comparing the HLA-A locus genotype with surface expression of HLA. Three cell lines showed complete lack of HLA expression associated with failure to express beta 2-microglobulin. In two other cell lines, loss of expression of HLA-A2 was observed, in spite of the presence of the gene in genomic DNA. Eleven cell lines gave a single HLA-A locus specificity on PCR typing. In one of these cell lines we have demonstrated the loss of an HLA-A locus gene in the tumor cell by comparison with DNA from a lymphoblastoid B-cell line derived from the same patient. These data indicate that at least three independent mechanisms were involved in the loss of HLA expression on the colorectal tumor cell lines. PMID- 8464899 TI - Antibody-promoted dimerization bypasses the regulation of DNA binding by the heme domain of the yeast transcriptional activator HAP1. AB - The yeast transcriptional activator HAP1 contains a DNA-binding domain homologous to the zinc finger of GAL4 and an adjacent regulatory domain that blocks DNA binding in the absence of the inducer heme. We show that short HAP1 fragments containing the zinc finger are unable to bind to DNA but can be rescued by antibody to the HAP1 zinc finger. These fragments are missing a coiled-coil sequence similar to that within the dimerization domain of GAL4 and dimerization domains of myosin heavy chain. We surmise that the antibody promotes DNA binding by bringing together two monomers. Interestingly, the antibody will also promote DNA binding of a larger HAP1 fragment containing the DNA-binding and the heme regulatory domains. This suggests that the regulatory domain acts by preventing dimerization of HAP1 in the absence of heme. Consistent with this view is an in vivo assay that also reveals that heme promotes HAP1 dimerization in yeast cells. PMID- 8464900 TI - Cloning of the cDNA encoding a myosin heavy chain B isoform of Xenopus nonmuscle myosin with an insert in the head region. AB - The complete amino acid sequence of Xenopus laevis nonmuscle myosin heavy chain B (MHC-B) has been deduced from overlapping cDNA clones isolated from an XTC cell library. RNA blots of various developmental stages, adult tissues, and XTC cells detect a single transcript of 7.5 kb which is expressed at similar levels throughout development. MHC-B mRNA was detected in XTC cells, heart, lung, spleen, and brain, at lower levels in ovary, testis, pancreas, stomach, liver, and eye, but not in kidney and skeletal muscle. Protein expression in adult tissues, as detected by immunoblot analysis, correlates well with mRNA expression. In chickens and humans, a fraction of the mRNA encoding the MHC-B isoform was found previously to contain a 10-amino acid insert at amino acid 211 near the ATP-binding site. As reported elsewhere, in the chicken this insert bearing isoform is nervous system-specific. The Xenopus sequence shows a 16-amino acid insertion at the same position; 7 of 16 residues are identical to those in the chicken and human insertion, and these identical residues include a consensus target sequence for cyclin-p34cdc2 kinase. In contrast to chicken, all frog tissues and embryonic stages tested contained the insert-bearing form, and no evidence for a non-insert-bearing MHC-B isoform was found in Xenopus. PMID- 8464901 TI - Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha 1(IX) collagen chains with a central deletion. AB - Type IX collagen, containing molecules of the three distinct polypeptides alpha 1(IX), alpha 2(IX), and alpha 3(IX), is an interesting hybrid extracellular matrix component in cartilage and eye tissues, with the properties of both a proteoglycan and a collagen. The alpha 1 (IX) chain has two forms, as a result of the tissue-specific utilization of two alternative promoters; the alpha 2(IX) chain carries a covalently attached glycosaminoglycan side chain. We have introduced a gene construct controlled by a tissue-specific promoter/enhancer and expressing a truncated alpha 1(IX) chain into mice. Examination of the offspring of two different founders revealed pathological changes similar to osteoarthritis in the articular cartilage of knee joints. In addition, mice homozygous for the transgene developed mild chondrodysplasia (i.e., mild dwarfism, anterior tonguing in the vertebral bodies, and ophthalmopathy). The relative ratio of transgene product to the endogenous alpha 1(IX) chain was approximately one in homozygotes and less than one in heterozygotes. Therefore, the phenotypic severity correlated well with the level of transgene expression. These findings suggest that mutations in type IX collagen genes may cause certain forms of osteoarthritis and chondrodysplasia in humans. PMID- 8464902 TI - High-molecular-weight proteins of nontypable Haemophilus influenzae mediate attachment to human epithelial cells. AB - Nontypable Haemophilus influenzae are Gram-negative bacilli that represent a common cause of human disease. These organisms initiate infection by colonizing the upper respiratory tract. Despite the essential role of colonization, the bacterial determinants of this process remain poorly defined. We recently identified a family of surface-exposed high-molecular-weight proteins of nontypable H. influenzae that are related to filamentous hemagglutinin, a critical adherence factor of Bordetella pertussis. The genes encoding the two such high-molecular-weight proteins (HMW-1 and HMW-2) expressed by a prototypic nontypable H. influenzae strain have now been cloned and sequenced. In this study we examined the role of the HMWs in adherence to human epithelial cells. We found that loss of expression of HMW-1 by the prototypic strain and a HMW-1-like protein in a heterologous nontypable H. influenzae strain markedly decreased the capacity to adhere. The absence of expression of both HMW-1 and HMW-2 in the prototypic strain or their homologs in the second strain was associated with a further decrease in adherence. Expression of either HMW-1 or HMW-2 in nonadherent laboratory strains of Escherichia coli resulted in acquisition of the adherence phenotype. These results indicate that both HMW-1 and HMW-2 and the homologous proteins from a second strain can mediate attachment. We speculate that these proteins and the related proteins in other nontypable H. influenzae isolates are important colonization factors. PMID- 8464903 TI - Mutant human cells defective in induction of major histocompatibility complex class II genes by interferon gamma. AB - Using immunoselection, we have isolated 11 independent mutant HT1080 fibrosarcoma cell lines defective in the induction by interferon gamma (IFN-gamma) of the expression of the human leukocyte antigen HLA-DRA. The mutations are recessive and fall into five complementation groups. All the mutants are affected mainly in the expression of major histocompatibility complex class II and invariant-chain genes. Type I mutants (three complementation groups) are completely defective in induction of the invariant-chain and class II HLA-DP, -DQ, -DR, and -DM genes, whereas type II mutants (two complementation groups) induce these genes weakly in response to IFN-gamma, in the order DPB > DRA > invariant chain. The induction by IFN-gamma of the mRNAs for class I, TAP1, LMP7, and 9-27 is partially defective and the induction of the proteins IRF-1 and ICAM-1 is normal in both types of mutants. All the mutants respond normally to IFN-alpha. The mutants are stable and thus can be used to clone the affected genes by reversion. PMID- 8464904 TI - Purification, characterization, and cDNA cloning of an NADPH-cytochrome P450 reductase from mung bean. AB - We report here the isolation and deduced amino acid sequence of the flavoprotein, NADPH-cytochrome P450 (cytochrome c) reductase (EC 1.6.2.4), associated with the microsomal fraction of etiolated mung bean seedlings (Vigna radiata var. Berken). An 1150-fold purification of the plant reductase was achieved, and SDS/PAGE showed a predominant protein band with an apparent molecular mass of approximately 82 kDa. The purified plant NADPH-P450 reductase gave a positive reaction as a glycoprotein, exhibited a typical flavoprotein visible absorbance spectrum, and contained almost equimolar quantities of FAD and FMN per mole of enzyme. Specific antibodies revealed the presence of unique epitopes distinguishing the plant and mammalian flavoproteins as demonstrated by Western blot analyses and inhibition studies. Peptide fragments from the purified plant NADPH-P450 reductase were sequenced, and degenerate primers were used in PCR amplification reactions. Overlapping cDNA clones were sequenced, and the deduced amino acid sequence of the mung bean NADPH-P450 reductase was compared with equivalent enzymes from mammalian species. Although common flavin and NADPH binding sites are recognizable, there is only approximately 38% amino acid sequence identity. Surprisingly, the purified mung bean NADPH-P450 reductase can substitute for purified rat NADPH-P450 reductase in the reconstitution of the mammalian P450-catalyzed 17 alpha-hydroxylation of pregnenolone or progesterone. PMID- 8464905 TI - Demonstration of ligand-dependent signaling by the erbB-3 tyrosine kinase and its constitutive activation in human breast tumor cells. AB - The predicted human erbB-3 gene product is closely related to epidermal growth factor receptor (EGFR) and erbB-2, which have been implicated as oncogenes in model systems and human neoplasia. We expressed the erbB-3 coding sequence in NIH 3T3 fibroblasts and identified its product as a 180-kDa glycoprotein, gp180erbB 3. Tunicamycin and pulse-chase experiments revealed that the mature protein was processed by N-linked glycosylation of a 145-kDa erbB-3 core polypeptide. The intrinsic catalytic function of gp180erbB-3 was shown by its ability to autophosphorylate in vitro. Ligand-dependent signaling of its cytoplasmic domain was established employing transfectants that express a chimeric EGFR/erbB-3 protein, gp180EGFR/erbB-3. EGF induced tyrosine phosphorylation of the chimera and promoted soft agar colony formation of such transfectants. These findings combined with the detection of constitutive tyrosine phosphorylation of gp180erbB 3 in 4 of 12 human mammary tumor cell lines implicate the activated erbB-3 product in the pathogenesis of some human malignancies. PMID- 8464906 TI - Human BMP sequences can confer normal dorsal-ventral patterning in the Drosophila embryo. AB - The type beta transforming growth factor family is composed of a series of processed, secreted growth factors, several of which have been implicated in important regulatory roles in cell determination, inductive interactions, and tissue differentiation. Among these factors, the sequence of the DPP protein from Drosophila is most similar to two of the vertebrate bone morphogenetic proteins, BMP2 and BMP4. Here we report that the human BMP4 ligand sequences can function in lieu of DPP in Drosophila embryos. We introduced the ligand region from human BMP4 into a genomic fragment of the dpp gene in place of the Drosophila ligand sequences and recovered transgenic flies by P-element transformation. We find that this chimeric dpp-BMP4 transgene can completely rescue the embryonic dorsal ventral patterning defect of null dpp mutant genotypes. We infer that the chimeric DPP-BMP4 protein can be processed properly and, by analogy with the action of other family members, can activate the endogenous DPP receptor to carry out the events necessary for dorsal-ventral patterning. Our evidence suggests that the DPP-BMP4 signal transduction pathway has been functionally conserved for at least 600 million years. PMID- 8464907 TI - Opioid peptides activate phospholipase D and protein kinase C-epsilon in chicken embryo neuron cultures. AB - The mu-opioid peptide morphiceptin stimulated a Ca(2+)-independent protein kinase C (PKC-epsilon) that is expressed both in embryonic day 6 chicken telencephalon and in derived neuronal cultures. This activation was seen as a 2-fold increase in the activity and level of cytosolic PKC-epsilon and as a transient increase in membrane-associated PKC-epsilon following morphiceptin treatment. Morphiceptin did not activate phospholipase C-mediated phosphatidylinositol hydrolysis but did transiently activate (2- to 3-fold) phospholipase D (PLD), as measured by phosphatidylethanol formation in neuron cultures derived from embryonic day 6 or day 7 cerebral hemispheres. This PLD activation could provide an alternative source of diacylglycerol for the activation of PKC-epsilon and was naloxone reversible and at least partially blocked by the tyrosine kinase inhibitor herbimycin A. Addition of phorbol 12-myristate 13-acetate stimulated both PLD and PKC-epsilon activities to a greater extent than opioids. The phorbol ester and insulin stimulation of PLD was also blocked by herbimycin. Both morphiceptin (in a naloxone-reversible manner) and phorbol ester increased phosphorylation of similar cytosolic proteins in intact cells, demonstrating a functional role for the PKC-epsilon activation by opioids. This is evidence that opioid receptors are transiently coupled to tyrosine kinase, PLD and PKC-epsilon activation and, by implication, to neuronal cell growth during brain morphogenesis. PMID- 8464908 TI - Experimental resolution of the free energies of aqueous solvation contributions to ligand-protein binding: quinone-QA site interactions in the photosynthetic reaction center protein. AB - Equilibrium binding free energies of 14 benzo-, naphtho-, and anthraquinone cofactors have been determined at the QA redox catalytic site of the purified photosynthetic reaction center protein from Rhodobacter sphaeroides solubilized in water (delta G degrees B,w), in hexane solution containing 30 mM water (delta G degrees B,hh), and after partial dehydration (delta G degrees B,dh) with magnesium sulfate. Our aim is to resolve the contributions of aqueous bulk phase solvation and protein hydration contributions to binding in order to characterize in detail the direct interactions between the ligands and protein at the QA site. This is accomplished by comparing the differences between delta G degrees B,w and delta G degrees B,hh (or delta G degrees B,dh) with the water to hexane solvent transfer free energies of the quinones (delta G degrees tr,Q). Values of delta G degrees tr,Q are determined separately in binary solution and range from 0.65 to 5.69 kcal/mol (1 cal = 4.184 J). The results are interpreted in terms of a thermodynamic cycle that links the species involved in the binding and solvent transfer equilibria. Values of delta G degrees B,hh -delta G degrees B,w are linearly correlated with -delta G degrees tr,Q (slope, 0.78 +/- 0.04; ordinate intercept, -0.13 +/- 0.12 kcal/mol). The deviation of the experimental slopes from the predicted value of unity is attributed in part to a systematic decrease of quinone thermodynamic activity in the aqueous binding medium relative to the aqueous phase in the binary partitioning solvent system. The difference between the quinone-QA site binding free energies measured in hydrated hexane and water is therefore related only to the difference in bulk phase quinone solvation, as given by 0.78 delta G degrees tr,Q. The linear relation obtained using delta G degrees B,dh -delta G degrees B,w has the same slope, but the intercept is decreased to -1.48 +/- 0.19 kcal/mol, indicating that quinone binding strengths in the hexane system are uniformly enhanced after partial dehydration. This suggests that the quinones encounter a common opposition to interaction with the site in the hydrated, relative to the partially dehydrated, state. The further utility of the method to directly assess ligand-site binding free energies is demonstrated with examples that address the contributions of molecular size and dipolar or hydrogen bond interactions to the binding of quinones at the QA site. PMID- 8464909 TI - Crystal structure of CATGGCCATG and its implications for A-tract bending models. AB - The single-crystal x-ray analysis of orthorhombic CATGGCCATG has revealed a previously unrecognized mode of intrinsic bending in DNA. The decamer shows a smooth bend of 23 degrees over the central four base pairs, caused by preferential stacking interactions at guanine bases. The bend is produced by a roll of base pairs along their long axes, in a direction that compresses the wide major groove of the double helix. This major-groove-compressing bend at GGC, plus the abundant crystallographic evidence that runs of successive adenine bases (A tracts) are straight and unbent, requires rethinking of the models most commonly invoked to explain A-tract bending. A decade of excellent experimental work involving gel migration experiments, cyclization kinetics, and nucleosome phasing has clearly established that introduction of short A-tracts into a general DNA sequence in synchrony with the natural repeat of the helix leads to bending. But it does not logically and inevitably follow that the actual bending is to be found within these introduced A-tracts or even at junctions with general-sequence B-DNA. PMID- 8464910 TI - Biocatalytic synthesis of acrylates in supercritical fluids: tuning enzyme activity by changing pressure. AB - Supercritical fluids are a unique class of nonaqueous media in which biocatalytic reactions can occur. The physical properties of supercritical fluids, which include gas-like diffusivities and liquid-like densities, can be predictably controlled with changing pressure. This paper describes how adjustment of pressure, with the subsequent predictable changes of the dielectric constant and Hildebrand solubility parameter for fluoroform, ethane, sulfur hexafluoride, and propane, can be used to manipulate the activity of lipase in the transesterification of methylmethacrylate with 2-ethyl-1-hexanol. Of particular interest is that the dielectric constant of supercritical fluoroform can be tuned from approximately 1 to 8, merely by increasing pressure from 850 to 4000 psi (from 5.9 to 28 MPa). The possibility now exists to predictably alter both the selectivity and the activity of a biocatalyst merely by changing pressure. PMID- 8464911 TI - Expression of the major protein kinase C substrate, the acidic 80-kilodalton myristoylated alanine-rich C kinase substrate, increases sharply when Swiss 3T3 cells move out of cycle and enter G0. AB - The expression of the major protein kinase C (PKC) substrate, originally called "80K" for acidic SDS/PAGE-observed 80-kDa PKC substrate and now called "MARCKS" for myristoylated alanine-rich C kinase substrate, in Swiss 3T3 fibroblasts changes strikingly (15- to 22-fold) during transitions of cell growth. Quiescent cells in G0 express high levels of MARCKS mRNA and protein. However, plating these cells in fresh medium at low density to stimulate multiple rounds of cell division caused a striking down-regulation of MARCKS expression. The mRNA level declined to a minimum of 4.5% compared with quiescent control cells 6 hr after plating, and protein levels declined during the same period to 6.5% of the control value. This rapid down-regulation was independent of PKC activation and length of exposure to trypsin (1-10 min) but required plating in medium containing fresh serum. MARCKS mRNA and protein levels remained down-regulated for 3 days, during which time the cells were actively progressing through the cell cycle as judged by fluorescence-activated cell sorting analysis. However, on reaching quiescence, the expression of MARCKS mRNA and protein increased markedly. Furthermore, the rate of recovery of MARCKS mRNA and protein levels was shown to be dependent on the supply of serum-derived growth factors in the medium. Addition of hydroxyurea to arrest the cells in S phase or at the G1/S boundary rather than G0 completely prevented the recovery of MARCKS protein. The down-regulation of MARCKS following plating and its serum-dependent recovery was also demonstrated in tertiary cultures of mouse embryo fibroblasts. The results suggest that MARCKS may play a role in the regulation of entry and exit of cells from G0. PMID- 8464912 TI - Epigenetic mechanisms of drug resistance: drug-induced DNA hypermethylation and drug resistance. AB - In a model system employing Chinese hamster V-79 cells, the DNA synthesis inhibitor 3'-azido-3'-deoxythymidine (BW A509U, AZT) was shown to induce genome wide DNA hypermethylation, low-frequency silencing of thymidine kinase (TK; EC 2.7.1.21) gene expression, and resistance to AZT. Twenty-four hours of exposure of V-79 cells to 150 microM AZT led to > 2-fold enhancement of genomic 5 methylcytosine levels and produced TK- epimutants at a rate approximately 43-fold above background. Such AZT-induced TK- epimutants were shown to be severely reduced in their capacity to activate AZT to its proximate antiviral form, AZT 5' monophosphate, as compared with the TK+ parental cell line from which they were derived. TK- clones isolated under these conditions were shown to be 9- to 24 fold more resistant to the cytotoxic effects of AZT than the parental TK+ cell line and showed collateral resistance to 5-fluoro-2'-deoxyuridine. Three of four TK- epimutants could be reactivated at very high frequency (8-73%) to the TK+ AZT sensitive phenotype by 24 hr of exposure to the demethylating agent 5 azadeoxycytidine (5-azadC), implying that drug-induced DNA hypermethylation, rather than classical mutation, was involved in the original gene-silencing event in these three clones. These 5-azadC-induced TK+ revertants concomitantly regained the ability to metabolize AZT to its 5'-monophosphate. RNA slot blot analyses indicated that the four AZT-induced TK- clones expressed 8.9%, 15.6%, 17.8%, and 11.1% of the parental level of TK mRNA. The three clones that were reactivatable by 5-azadC showed reexpression of TK mRNA to levels 84.4%, 51.1%, and 80.0% that of the TK+ parental cell line. These experiments show that one potential mechanism of drug resistance involves drug-induced DNA hypermethylation and resulting transcriptional inactivation of cellular genes whose products are required for drug activation. PMID- 8464913 TI - Molecular characterization of an operon required for pertussis toxin secretion. AB - Mutants of Bordetella pertussis which are defective in secretion of pertussis toxin were isolated and characterized. The region of the B. pertussis chromosome identified by mutagenesis as playing a role in transport of pertussis toxin was sequenced. Analysis of this region revealed eight open reading frames, seven of which predict a protein exhibiting homology with one of the VirB proteins of Agrobacterium tumefaciens, which are involved in the transport of the T-DNA molecule across bacterial and plant membranes. Thus a set of accessory proteins are most likely involved in the secretion of pertussis toxin, and these proteins appear to be members of a family of proteins involved in the secretion of macromolecules from bacteria. PMID- 8464914 TI - Electrophysiological tests of neural models: evidence for nonlinear binocular interactions in humans. AB - Evoked cortical potentials were used to test neural models of binocular interactions in humans. The critical feature that distinguished between basic models was whether the two monocular signals combined linearly or nonlinearly. Stimuli were presented separately and simultaneously to two eyes with the relative temporal phase parametrically varied. Fourier analysis was applied to the recorded electroencephalogram to measure the frequency response of the visual cortex to this stimulation. Comparisons of the models' predictions with the experimental results indicate that the greatest contribution to the cortical response originates in a neural pathway that contains nonlinear binocular combination, and a smaller contribution originates in a pathway with linear binocular combination. Current models, based on psychophysical studies of humans and on single-cell neurophysiological investigations of cats, are inadequate to explain these results. A model of binocular interaction is proposed that does account for the present findings and is also supported by neurophysiological studies on monkeys. This model, which contains both nonlinear and linear binocular interactions, has profound implications for perceptual processing. PMID- 8464915 TI - Identification of sequence elements in mouse calbindin-D28k gene that confer 1,25 dihydroxyvitamin D3- and butyrate-inducible responses. AB - We have examined the 5' flanking region of the mouse calbindin-D28k gene and identified a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-responsive element by deletion mutant analysis of the native promoter as well as by studies with a heterologous thymidine kinase (TK) promoter. The segment between residues -200 and -169 was found to confer a dose-dependent 1,25-(OH)2D3 responsiveness through the TK promoter in Ros 17/2.8 cells as well as in CV-1 cells cotransfected with pAV-hVDR (human vitamin D receptor expression vector). This region contains sequences homologous to the rat osteocalcin vitamin D response element (VDRE). Incubation of this element with nuclear extracts from 1,25-(OH)2D3-treated Ros 17/2.8 cells or from 1,25-(OH)2D3-treated COS cells that had been transfected with pAV-hVDR resulted in a specific protein-DNA interaction. In addition to 1,25 (OH)2D3, sodium butyrate, a differentiating agent, has also been found to modulate expression of calbindin-D28k. Deletion analysis of the mouse calbindin D28k promoter as well as studies with a heterologous TK promoter resulted in identification of a butyrate-responsive element between -180 and -150 that was found to bind specifically to nuclear factors from butyrate-treated Ros 17/2.8 cells. This butyrate-responsive element may represent a genetic element acted upon by enhancer binding proteins. In summary, the 5' flanking region of the mouse calbindin-D28k gene contains responsive elements that interact with nuclear factors and may mediate, at least in part, the enhanced expression of this gene by 1,25-(OH)2D3 and butyrate. PMID- 8464916 TI - Observing the helical geometry of double-stranded DNA in solution by fluorescence resonance energy transfer. AB - The efficiency of fluorescence resonance energy transfer (FRET) between fluorescein and rhodamine covalently attached to both 5' termini of a series of double-stranded DNA species (ranging from 8 to 20 bp) was measured. FRET efficiency varied with a dependence compatible with dye-to-dye distances (R) calculated on the basis of double-stranded B-DNA structure; the helical geometry of double-stranded DNA in solution is clearly evident. The experimental data were consistent with a 1/[1 + (R/R0)6] dependence of FRET efficiency characteristic for the Forster dipole-dipole mechanism. The thermal dissociation of the strands of the duplex DNA species can be followed by using FRET, and from these data we have been able to obtain enthalpies of duplex formation in good agreement with earlier measurements using alternative techniques. FRET measurements at very different salt concentrations can be accurately compared. We conclude that FRET is a reliable and valuable method for studying structure and conformational transitions in nucleic acids. PMID- 8464917 TI - Markedly prolonged incubation period of hepatitis B in a chimpanzee passively immunized with a human monoclonal antibody to the a determinant of hepatitis B surface antigen. AB - The protective efficacy of a human monoclonal antibody directed against the a determinant of hepatitis B virus (HBV) surface antigen was studied in a chimpanzee. A single high dose of 5 mg/kg (body weight) of monoclonal antibody SDZ OST 577 was intravenously administered to a chimpanzee, followed by intravenous challenge with 10(3.5) chimpanzee infectious doses of a wild-type HBV, the MS-2 strain (ayw subtype). The passively acquired antibody to HBV surface antigen could be detected for 40 weeks. Serum HBV DNA tested by a "nested" polymerase chain reaction assay was negative through the 36th week after virus challenge but became positive by the 38th week. The chimpanzee subsequently developed acute hepatitis B approximately 1 year after challenge. The nucleotide sequence of the a determinant of the surface gene of the replicated virus was identical with that of the inoculated wild-type virus. Thus, a human monoclonal antibody directed against the a determinant of HBV surface antigen delayed but did not prevent experimental infection of HBV and hepatitis in the chimpanzee. Our results indicate an incomplete ability of this antibody to protect against HBV infection in vivo after a single infusion. PMID- 8464918 TI - In vitro assembly of multiprotein complexes containing alpha, beta, and gamma tubulin, heat shock protein HSP70, and elongation factor 1 alpha. AB - We have isolated two sets of multiprotein complexes from supernatants from high speed centrifugation of nocodazole-arrested CHO cells. One set, assembled in vitro after a 37 degrees C incubation in the presence of ATP or GTP, is composed of equivalent amounts of alpha- and beta-tubulin and a 50-kDa protein, provisionally identified as elongation factor 1 alpha. These complexes, which are heterogeneous in size when analyzed by sucrose gradient ultracentrifugation, also contain the cognate form of heat shock protein HSP70 and gamma-tubulin, a tubulin isoform of low abundance, along with other proteins known to be involved in the regulation of mitosis. Similar but distinct complexes assemble in vitro if the same extracts are incubated at 37 degrees C without added nucleotides; multiprotein complexes generated under these conditions lack HSP70 but contain instead a 43-kDa protein identified as an actin isoform. Both sets of assembled complexes exhibit a globular substructure when analyzed by electron microscopy, and their size distribution suggests that they assemble by the step-wise addition of smaller precursors. The properties of these multiprotein complexes and their presence in cells arrested in a stage between prophase and metaphase suggest that they may be precursors to mitotic centrosomes and are possibly involved in mitotic spindle nucleation. PMID- 8464919 TI - Carbohydrate binding activities of Bradyrhizobium japonicum: unipolar localization of the lectin BJ38 on the bacterial cell surface. AB - A polyclonal antiserum generated against the Bradyrhizobium japonicum lectin BJ38 was characterized to be specifically directed against the protein. Treatment of B. japonicum cells with this antiserum and subsequent visualization with transmission electron microscopy and both conventional and confocal fluorescence microscopy revealed BJ38 at only one pole of the bacterium. BJ38 appeared to be organized in a tuft-like mass, separated from the bacterial outer membrane. BJ38 localization was coincident with the attachment site for (i) homotypic agglutination to other B. japonicum cells, (ii) adhesion to the cultured soybean cell line SB-1, and (iii) adsorption to Sepharose beads covalently derivatized with lactose. In contrast, the plant lectin soybean agglutinin labeled the bacteria at the pole distant from the bacterial attachment site. These results indicate that the topological distribution of BJ38 is consistent with a suggested role for this bacterial lectin in the polar binding of B. japonicum to other cells and surfaces. PMID- 8464920 TI - Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. AB - The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development--granulocytes, macrophages, and dendritic cells--can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF. PMID- 8464921 TI - An 83-nucleotide promoter of the acetylcholine receptor epsilon-subunit gene confers preferential synaptic expression in mouse muscle. AB - The expression of the acetylcholine receptor epsilon-subunit gene is restricted to the endplate of adult muscle fibers. We have started to study the regulatory elements of the epsilon-subunit gene promoter that are important for its synaptic expression. We used, for this purpose, a rapid method of in vivo expression after DNA injection into the muscle tissue [Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A. & Felgner, P. L. (1990) Science 247, 1465-1468]. Our results show that a construction containing 83 nucleotides upstream from the transcription start site is sufficient to obtain preferential endplate expression. Moreover, mutation of a MyoD binding site located around position-70 does not alter this synaptic expression. We also studied the expression of this promoter in vitro in muscle primary cultures and showed the presence of a positive element between positions -122 and -83. Comparison of in vivo and in vitro results reveals that the elements important for in vivo localization at the synapse and in vitro expression in cultured muscle cells may differ. PMID- 8464922 TI - Presumptive Renshaw cells contain decreased calbindin during recovery from sciatic nerve lesions. AB - A subpopulation of calbindin-immunoreactive neurons in lamina VII of the spinal cord has been identified by its location as Renshaw cells, the anatomical substrate for recurrent inhibition. The expression of calbindin (28 kDa) in these calbindin-containing rat ventral horn interneurons was studied with immunocytochemistry after sciatic nerve injuries. One week after axotomy calbindin immunoreactivity was strongly reduced on the lesioned side between levels L4 and L6, while calbindin-containing neurons and fibers were still numerous contralaterally and cranially to the lesioned levels. With the progression of regeneration, calbindin-immunoreactive neurons reappeared, reaching a normal distribution 6-8 weeks after the crush. Similar changes could be mimicked by the intramuscular administration of botulinum toxin. These results suggest that calbindin expression in putative Renshaw cells of the spinal cord might be functionally responsive and that maintenance of calbindin expression may depend on the integrity of motoneurons and neuromuscular transmission. PMID- 8464923 TI - Chromosomal localization of glutamate receptor genes: relationship to familial amyotrophic lateral sclerosis and other neurological disorders of mice and humans. AB - Receptors for the major excitatory neurotransmitter glutamate may play key roles in neurodegeneration. The mouse Glur-5 gene maps to chromosome 16 between App and Sod-1. The homologous human GLUR5 gene maps to the corresponding region of human chromosome 21, which contains the locus for familial amyotrophic lateral sclerosis. This location, and other features, render GLUR5 a possible candidate gene for familial amyotrophic lateral sclerosis. In addition, dosage imbalance of GLUR5 may have a role in the trisomy 21 (Down syndrome). Further characterization of the murine glutamate receptor family includes mapping of Glur-1 to the same region as neurological mutants spasmodic, shaker-2, tipsy, and vibrator on chromosome 11; Glur-2 near spastic on chromosome 3; Glur-6 near waltzer and Jackson circler on chromosome 10; and Glur-7 near clasper on chromosome 4. PMID- 8464924 TI - Molecular cloning and expression of cDNA for mammalian translation initiation factor 5. AB - Eukaryotic translation initiation factor 5 (eIF-5) catalyzes the hydrolysis of GTP bound to the 40S ribosomal initiation complex (40S.AUG.Met-tRNAf-eIF-2.GTP) with the subsequent joining of a 60S ribosomal subunit resulting in the formation of a functional 80S initiation complex. A rat cDNA that encodes eIF-5 has been isolated and expressed in Escherichia coli to yield a catalytically active eIF-5 protein. The 3.55-kb cDNA encodes a protein of 429 amino acids (calculated M(r) 48,926) with properties that are similar to eIF-5 isolated from rabbit reticulocyte lysates. The deduced amino acid sequence of eIF-5 contains sequence motifs characteristic of proteins of the GTPase superfamily. PMID- 8464925 TI - Two distinct gene subfamilies within the family of cysteine protease genes. AB - A cDNA clone for a physiologically regulated Tetrahymena cysteine protease gene was sequenced. The nucleotide sequence predicts that the clone encodes a 336 amino acid protein composed of a 19-residue N-terminal signal sequence followed by a 107-residue propeptide and a 210-residue mature protein. Comparison of the deduced amino acid sequence of the protein with those of other cysteine proteases revealed a highly conserved interspersed amino acid motif in the propeptide region of the protein, the ERFNIN motif. The motif was present in all of the cysteine proteases in the data base with the exception of the cathepsin B-like proteins, which have shorter propeptides. Differences in the propeptides and in conserved amino acids of the mature proteins suggest that the ERFNIN proteases and the cathepsin B-like proteases constitute two distinct subfamilies within the cysteine proteases. PMID- 8464926 TI - Association of GAD-65, but not of GAD-67, with the Golgi complex of transfected Chinese hamster ovary cells mediated by the N-terminal region. AB - Glutamic acid decarboxylase (GAD) is the enzyme responsible for synthesis of the neurotransmitter gamma-aminobutyric acid in neurons and pancreatic beta cells. It is represented by two isoforms, GAD-65 and GAD-67, which are the products of two different genes and differ substantially only at their N-terminal regions. GAD-65 is a dominant autoantigen in stiff-man syndrome and insulin-dependent diabetes mellitus. In neurons and beta cells, GAD is concentrated around synaptic vesicles and synaptic-like microvesicles, respectively, as well as in the area of the Golgi complex. The mechanisms responsible for specific targeting of GAD to these organelles are not yet understood. The elucidation of the mechanism of subcellular targeting of GAD may be relevant to understanding its role as an autoantigen. In this study, the cloned genes for GAD-65 and GAD-67 were expressed separately in Chinese hamster ovary (CHO) cells and COS cells. While GAD-67 had a diffuse cytoplasmic localization, GAD-65 had a punctate distribution, with most of the immunoreactivity being concentrated in the area of the Golgi complex. A chimeric protein in which the 88 N-terminal amino acids of GAD-67 were replaced by the 83 N-terminal amino acids of GAD-65 was targeted to the Golgi complex, indicating that the N-terminal region of GAD-65 contains a targeting signal sufficient for directing the remaining portion of the molecule, highly similar in GAD-65 and GAD-67, to the Golgi complex-associated structures. PMID- 8464927 TI - Dual control of heat shock response: involvement of a constitutive heat shock element-binding factor. AB - Heat shock factor (HSF) has been implicated as the key regulatory protein in the heat shock response. Our studies on the response of rodent cells to heat shock or sodium arsenite indicate that a high level of HSF-DNA-binding activity, by itself, is not sufficient for the induction of hsp70 mRNA synthesis; furthermore, a high level of HSF binding is also not necessary for this induction. Analysis of the binding of protein factors to the heat shock element (HSE) in extracts of stressed rodent cells indicates that the regulation of heat shock response involves the heat-inducible HSF and a constitutive HSE-binding factor. Our results also suggest that overexpression of human hsp70 may decrease the level of heat-induced HSF-HSE-binding activity in rat cells. PMID- 8464928 TI - Soluble antigen profoundly reduces memory B-cell numbers even when given after challenge immunization. AB - The splenic B-cell repertoire of unimmunized C57BL/6 mice can be examined for anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) B cells of relatively high affinity by using a dual strategy. First, limiting numbers of splenocytes are polyclonally activated by Escherichia coli lipopolysaccharide and a mixture of interleukins 2, 4, and 5 in the presence of 3T3 filler cells, thus ensuring that many B-cell clones switch to IgG1 antibody production. Second, an enzyme-linked immunosorbent assay is geared to register only higher-affinity antibody by (i) detecting only bivalent IgG1 antibody and ignoring IgM and (ii) using a lowly substituted NP conjugated protein as the capture layer. Naive spleens contain very few higher affinity anti-NP B cells thus defined, but thymus (T)-dependent immunization causes the appearance of approximately 10(5) per spleen within 2 weeks. The development of these clonable anti-NP antibody-forming cell precursors can be virtually eliminated by a single injection of 1 mg of soluble, freshly deaggregated NP2-human serum albumin (HSA). This toleragen works not only if injected prior to challenge immunization, but even if given up to 6 days later. Soluble HSA works partially but not nearly as well as NP2-HSA, suggesting the possibility that the toleragen must act on T and B cells. NP conjugated to irrelevant carriers achieved partial tolerance in only one of four experiments. The studies demonstrate the need for continuing T-cell help throughout the process of memory B-cell generation. They also show that those recently activated T cells involved in this process can be silenced in vivo by soluble toleragen. PMID- 8464929 TI - Noninvasive somatosensory homunculus mapping in humans by using a large-array biomagnetometer. AB - To validate the feasibility of precise noninvasive functional mapping in humans, a large-array biomagnetometer was used to map the somatosensory cortical locations corresponding to numerous distinct tactile sites on the fingers, hand, arm, and face in different subjects. Source localizations were calculated by using a single equivalent current dipole (ECD) model. Dipole localizations were transposed upon the corresponding subject's magnetic resonance image (MRI) to resolve the anatomic locus of the individual dipoles within a given subject. Biomagnetic measurements demonstrated that (i) there were distinct separations between the ECD locations representing discrete sites on the face and hand; (ii) the ECD localizations from facial sites clustered in a region inferior to ECD localizations from hand and digit sites; and (iii) there was clear spatial resolution of ECD locations representing closely spaced tactile sites on the hand and face. The ability of magnetoencephalography (MEG) to provide high-resolution spatial maps of the somatosensory system noninvasively in humans should make MEG a useful tool to define the normal or pathological organization of the human somatosensory system and should provide an approach to the rapid detection of neuroplasticity. PMID- 8464930 TI - Redox-activated expression of the cytosolic copper/zinc superoxide dismutase gene in Nicotiana. AB - Superoxide dismutases (SODs; superoxide: superoxide oxidoreductase, EC 1.15.1.1) play a key role in protection against oxygen radicals, and SOD gene expression is highly induced during environmental stress. To determine the conditions of SOD induction, the promoter of the cytosolic copper/zinc SOD (Cu/ZnSODcyt) gene was isolated in Nicotiana plumbaginifolia and fused to the beta-glucuronidase reporter gene. Oxidative stress is likely to alter the cellular redox in favor of the oxidized status. Surprisingly, the expression of the Cu/ZnSODcyt gene is induced by sulfhydryl antioxidants such as reduced glutathione, cysteine, and dithiothreitol, whereas the oxidized forms of glutathione and cysteine have no effect. It is therefore possible that reduced glutathione directly acts as an antioxidant and simultaneously activates the Cu/ZnSODcyt gene during oxidative stress. PMID- 8464932 TI - Overview of substance abuse. AB - Psychoactive substances have been used by humans from the earliest recorded times, and evidence shows that from the beginning some people have used drugs excessively, thus developing problems. From the 1960s to the 1980s, there has been a dramatic upswing in the use of alcohol and illicit substances, but some evidence demonstrates that this trend is beginning to reverse. Current substance abuse is estimated to cost US society about $152 billion and cause over 75,000 deaths annually. Research and treatment efforts have increased significantly over the past two decades. Although the exact cause of substance abuse disorders is unknown, evidence indicates that it is a complex interaction between biologic predispositions, and psychologic and social factors. The majority of research seems to indicate that at least in a subtype of patients with more severe abuse, genetic factors appear to be the single most important influence. Considerable research is underway to further clarify these factors, and it is reasonable to expect that we will soon have a much clearer understanding of the cause of these disorders. In turn, this understanding should lead to a better understanding of the optimal treatment for the millions of patients and families afflicted with substance abuse disorders. PMID- 8464933 TI - The twelve steps. A pathway to recovery. AB - Alcoholics Anonymous and its 12 Steps and 12 Traditions have arisen out of the experiences of recovery of alcoholics. It offers an important treatment option to the clinician who sees destructive compulsive disease in his or her practice. Despite their nonscientific, nonrational approach, AA and other 12-step programs have evolved to offer a set of attitudes, beliefs, and behaviors that can facilitate change in this group of patients. AA is the forerunner of the others and offers as its most important characteristics an unconditional acceptance of the patient's alcoholism, an unshaken belief in the concept of alcoholism as a disease, and support to foster a healthy dependence in the alcoholic. The recovery of an alcoholic involves a fairly long initial stage in which denial about alcoholism is broken down with slow and halting identity change. This characteristic underscores the primitive level of ego development in the alcoholic and the need for much continuing support, nurturance, and tolerance. Clinicians can be an important part of this support network by working with AA and other 12-step groups to help break down denial in the patient and direct individuals to the appropriate program. By allying themselves with this method and groups, clinicians will be making powerful statements about their beliefs and attitudes toward these destructive illnesses. PMID- 8464931 TI - Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. AB - Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6. PMID- 8464934 TI - Alcohol abuse. A family disease. AB - Alcohol problems have a serious impact on families. Physicians who identify alcohol-abusing persons in their practices will note that these people belong to families who seem "stuck" in a confusing family situation with no ready solution. Research and clinical observations have demonstrated that families adopt roles, rules, and interactional patterns around the alcohol abuse problems that can be destructive to individual development. These consequences of alcohol abuse are particularly troubling when we consider that family dysfunction, like the disease itself, is transmitted from generation to generation. Physicians can be most helpful to these families when they understand how to identify the presence of alcohol use problems, evaluate the impact on both the alcohol abuser and the family members, and facilitate the necessary treatment for these patients. PMID- 8464935 TI - Substance abuse among women. AB - Physicians' attitudes are important in dealing with issues of substance abuse in women. The primary care physician is in a unique position to take advantage of the doctor-patient relationship and initiate diagnosis and treatment of substance abuse. When the primary care physician is supportive of the patient, both begin from a position of strength. Patients are no more to blame for contracting the disease state than for getting other medical conditions for which they are at risk. Treatment of substance abuse in women must acknowledge that significant differences exist between men and women patients. Most treatment programs have been based on research studies in men. Current efforts are under way to update the information necessary to deal effectively with the problem of substance abuse among women. PMID- 8464936 TI - Adolescent substance abuse. Recognition and early intervention. AB - Adolescent substance abuse is a common problem, with 90% of high school seniors reporting alcohol use and nearly half reporting some illicit drug use. Substance abuse interferes with the developmental tasks of adolescence: establishing an adult identity, achieving independence from parents and family, and learning to form intimate relationships with others. Although not all adolescent substance abuse leads to chemical dependency, even initial experimentation can have disastrous or fatal consequences. The early signs and symptoms of substance abuse are subtle, frequently presenting as behavioral changes, and less often as physical or laboratory findings. Early stages of substance abuse may be treated by the primary care physician in outpatient treatment settings. More advanced stages usually require inpatient treatment and should be referred to specialists in adolescent substance abuse treatment. Family involvement is a critical part of the treatment process. In addition to a key role in the early diagnosis, intervention, and referral of substance abuse problems, the primary care physician is an important source of support, reinforcement, and continuity in the aftercare program once the adolescent has completed initial substance abuse treatment. PMID- 8464937 TI - Recognition and treatment of substance abuse in the elderly. AB - Elderly people do use substances to alter mood and states of awareness. Detection is difficult because presenting symptoms are often those that are commonly associated with aging itself. All patients who present with symptoms of self neglect, falls, cognitive and affective impairment, and social withdrawal should be screened for substance abuse. The CAGE and MAST, although not perfect, can be used. When abuse is found, the elderly should be treated as aggressively as their younger counterparts, with slow, careful detoxification and the use of some form of group therapy, such as AA. PMID- 8464938 TI - Substance abuse among minority populations. AB - Substance abuse problems and their solutions not only vary considerably depending on the ethnicity of the patient, but also are influenced by factors such as age, gender, education, and socioeconomic status. Familiarity with the epidemiology of substance abuse problems of different sociocultural groups can help the clinician better understand and anticipate the needs of the patient population she or he is serving. The five-part sociocultural assessment model provides a framework to help the practitioner assess the sociocultural needs of an individual patient. Application of this model can help reveal the individual patient's beliefs, motivations, and sociocultural strengths and liabilities with regard to substance abuse. With this information, the clinician can then better address special treatment needs. PMID- 8464939 TI - Dual diagnosis. AB - Although the problem of patients with dual diagnoses is not new, it has only been in the last few years that their unique and complex problems have begun to be addressed. This recognition coincides with society's concern regarding the magnitude of substance abuse problems in general. Currently, treatment consists of integrating concepts from substance abuse and mental health fields. This integration may improve the therapeutic outcome for these patients. As more experience is gained in this specialty, it is hoped that new treatment concepts will evolve that will more powerfully address the interactive aspect of substance abuse and psychiatric disorders. PMID- 8464940 TI - The pharmacology of mood-altering drugs of abuse. AB - The majority of mood-altering drugs that have significant abuse potential possess several properties that contribute to drug dependence, including behavioral reinforcing and rewarding actions, tolerance to behavioral effects, and development of physical dependence. Although various drug classes may differ in the relative importance of these properties, it is generally recognized that they form the basis of abuse and misuse of many drugs. These phenomena are not the result of novel or unique drug actions but represent biochemical or neurochemical modulation of normal functional mechanisms in the central nervous system. PMID- 8464941 TI - Substance abuse during pregnancy. AB - Use and abuse of both licit and illicit drugs is common. Although certain variables can appropriately serve as markers for increased risk, the possibility of substance abuse should be considered in all pregnant women. Alcohol is the leading identified cause of teratogenesis by drugs or environmental agents; most other drugs of abuse do not increase the risk of congenital malformations on a large scale. Substance abuse can produce significant degrees of toxicity in both pregnant women and their offspring. Screening and counseling of pregnant women concerning past and present use of tobacco, alcohol, and illicit drugs should be routine. Prenatal care must include increased surveillance for drug-related complications; coordinated, comprehensive, family-oriented drug treatment; and social services. Rehabilitation and support efforts should continue after delivery and address issues that lead to and maintain patterns of abuse. The drug exposed neonate must be anticipated and evaluated with a knowledge of the maternal drug abuse history and specific drug risks, including neonatal abstinence syndrome. Continuing care of the child should address the increased risk of developmental and behavioral problems from both prenatal exposures and continuing socioenvironmental barriers. PMID- 8464942 TI - Impaired physicians. AB - The prevalence of chemical dependency among physicians in the United States is probably the same as for the general population, about 8% to 12%. Organized medicine has responded to this problem by establishing programs to help these impaired physicians. Chemically impaired physicians can be treated and followed by structured programs with favorable results. To prevent the tragic outcomes of untreated physician impairment due to chemical dependency, nonimpaired physicians must learn about this problem and take the appropriate actions. Impaired physicians need not fear treatment, for it can help them return to a productive career. To further lessen the tragic effects of substance abuse among physicians, proactive strategies of prevention should be adopted by medical schools, residency programs, hospital staffs, and similar physician organizations. PMID- 8464943 TI - Illicit drugs of abuse. AB - Primary care physicians should be aware of the popular street drugs being abused in their practice areas. A basic understanding of the drugs and their use will make the physician more credible in the eyes of the patient. Patients may present a variety of symptoms associated with their chemical abuse. Specific presenting complaints, physical findings, and laboratory tests will help establish the diagnosis of substance abuse. After the diagnosis is established, a drug treatment program can bring about a seemingly miraculous recovery from the disease of chemical dependency, to the lasting benefit of the patient and the patient's family. PMID- 8464944 TI - Prescription drug abuse. AB - Misuse and abuse of prescription medication can be a difficult clinical area for physicians. Prior to prescribing any mood-altering medication, the physician should screen for patients at risk for abuse by asking about an individual or family history of alcohol or other drug abuse. When prescribing a psychoactive medication, the clinician should be sure that there is a clear clinical indication and should identify a therapeutic end-point and time limit. Nonpharmacologic interventions should be emphasized when appropriate. When misuse rather than abuse is suspected, the intervention may be one of education and simplification or clarification of the therapeutic contract. Physicians should recognize apparent drug-seeking behaviors and feel comfortable questioning for possible alcohol or other drug-related problems so that drug abuse can be identified as an additional problem requiring attention. Physicians should be comfortable with assertively denying drugs to drug-seeking patients when appropriate. Although sometimes difficult, to do otherwise would be to facilitate the continuation of a potentially serious problem. The potential frustration and aggravation of dealing with prescription drug abuse can be minimized by thoughtful attention to prevention, the development of a rational style of prescribing, and the appropriate use of intervention. PMID- 8464945 TI - Educational strategies for clinicians. AB - Largely because of a lack of training, many primary care physicians are unaware of how they can prevent, detect, or manage substance abuse within their clinical practice. The educational process used to develop a teaching unit can be simplified by initially asking a few directed questions. The answers to these questions determine what needs to be taught while facilitating the subsequent steps of determining learning goals and objectives and selecting appropriate teaching materials and strategies. Evaluating the teaching unit on at least a cursory level provides useful information for future planning. A variety of curriculum manuals and clinical text parts can be readily incorporated into teaching units. These same sources can alternatively be adapted to an individual's own self-directed course of study. Incorporation of experimental educational strategies is especially useful in substance abuse instruction. Including recovering individuals, attendance at self-help group meetings, and role play exercises are all useful experimental strategies for engaging the learner. Tapping into organizational resources and networking with others involved in similar activities enhances one's potential through the sharing of information and through the synergism created by networking with others. PMID- 8464946 TI - Office evaluation and treatment of the dependent smoker. AB - Nicotine addiction is the most prevalent of all substance dependence, resulting in profound medical, social, and psychologic costs. Evidence supporting the addictive nature of nicotine is compelling. Recognition of this addiction has opened treatment options not currently available, including pharmacologic options. Physicians can contribute to cessation success even with minimal interventions. For those interested in stronger interventions, careful assessment of the smoker is essential. This assessment should identify the degree of nicotine dependence, the presence of negative affect related to cessation, and the pervasiveness of meaning of tobacco in the patient's life. Treatment options include white knuckle or will power quitting, guided self-treatment, referral, and office cessation with or without pharmacologic support. A four-visit protocol that includes (1) recruitment, (2) assessment, (3) treatment, and (4) relapse prevention is described. PMID- 8464947 TI - Early recognition of chemical dependence. AB - Chemical dependence is a leading cause of morbidity and death in the United States. At least 20% of patients seen by primary care physicians in both the outpatient and inpatient setting are chemically dependent. Up to 90% of these patients go undiagnosed by their primary physicians. Chemical dependence is defined as a chronic, progressive illness characterized by the repeated and persistent use of alcohol or drugs despite negative health, family, work, financial, or legal consequences. Primary care physicians are in an ideal position to detect chemical dependence at its earliest stages, when irreversible medical consequences and death are most likely preventable. Alcohol is the most common drug of abuse. Improving the rate of recognition of chemical dependence depends on being familiar with the constellation of physical, mental, and social indicators. Early medical manifestations of alcoholism common in the primary care setting include: gastric complaints, elevated blood pressure, palpitations, traumatic injuries, headaches, impotence, and gout. Early psychosocial manifestations common in both alcohol and drug dependence include anxiety, depression, insomnia, persistent relationship conflicts, work or school problems, and financial or legal problems. Particularly useful laboratory indicators of alcoholism include elevated levels of GGT and MCV, both displaying high specificity, with the GGT level being the most sensitive. Similarly specific laboratory tests for drug dependence are not available. Any patient presenting with any of the above medical, psychosocial, or laboratory manifestations should be screened for chemical dependence. The CAGE questionnaire for alcoholism, a four-question test, is particularly well suited to the primary care setting, where it can be administered in fewer than 60 seconds. The CAGE has demonstrated high sensitivity (in the 80% range) and specificity (approximately 85%) for alcoholism. Comparably convenient instruments do not yet exist for drug dependence, although a 28-item instrument, the DAST (Drug Abuse Screening Test), has demonstrated high sensitivity and specificity for drug abuse. PMID- 8464948 TI - Dealing with substance misuse, abuse, and dependency. AB - Using this model, clinicians can enhance skills for screening, assessing, and aiding at-risk and problem drinkers. The six-step model incorporates the transtheoretic model of behavior change and uses motivational interviewing strategies and the concept of brief, early interventions. Primary care physicians can apply this model for patients in their offices and in hospital settings where they provide continuity of care. Furthermore, physicians can also use this model to intervene successfully at both the secondary and tertiary levels of prevention. In essence, this model uses a variety of strategies to aid at-risk and problem drinkers. These strategies can help patients and families overcome their ignorance about the role that alcohol plays in their lives and to motivate them toward a healthier lifestyle. Physicians can select strategies that range from simple advice to motivational counseling. Depending on the presenting problems and the likelihood and severity of an alcohol problem, the physician can select strategies described in this model to develop an individualized approach to motivate at-risk and problem drinkers to move through the phases of behavioral change: precontemplation, contemplation, preparation, action, and maintenance. Such an approach can help patients take responsibility for changing their drinking habits. PMID- 8464949 TI - Outpatient management of alcohol abuse. AB - Patients with alcohol problems come to their primary care physicians at different points along the spectrum of experiences with alcohol; therefore, physicians need to be able to respond with a variety of interventions. In addition, patients present in different stages of change, and physicians need to be aware of where the patient is in that continuum. Evidence shows that less intensive, outpatient treatment may be as beneficial as inpatient treatment for some patients and that primary care physicians can offer some of their patients relatively simple interventions that are effective. Medications such as disulfiram offer little in the treatment of alcoholism but may be of benefit in selected situations. Of greater benefit are more complex psychosocial interventions carried out by a team of health care professionals. PMID- 8464950 TI - Principles and practice of detoxification. AB - Detoxification is the medical care that safely carries the patient through withdrawal. It is normally not an end point but is a step toward rehabilitation. Protocols should be tailored to meet the needs of individual patients. PMID- 8464951 TI - The hospital treatment of alcoholism and drug addiction. AB - Inpatient treatment of alcoholism is an option indicated by certain clinical criteria. The American Society of Addiction Medicine suggests four levels of care, and six assessment dimensions determine which level of care is indicated. An addiction medicine physician can consult with the primary care physician to recommend appropriate placement in difficult cases. Abstinence is a primary goal of treatment; for without abstinence, no other recovery will be possible. The remaining goals of recovery are detoxification, medical evaluation, stabilization of life-threatening emotional issues, education, identification of barriers to recovery, readjustment of behavior toward recovery, and orientation and membership in a self-help group. Successful family contributions can make the difference between success or failure of treatment goals; the role the family plays in recovery is discussed. Treatment for family members is important; the physical, emotional, and spiritual effects on family members can be just as profound on them as they are on the alcoholic. Continuing care maintains the link between the patient and the professional recovery community after discharge and is appropriate for all patients. Extended care allows for structured support of sobriety and often further progress through psychosocial issues identified during the initial treatment phase (i.e., abuse, molestation, unresolved grief). Extended care is indicated for patients requiring further structured assistance in early recovery. A large variety of treatment options are available once the decision has been made to hospitalize the patient. PMID- 8464953 TI - Light visor treatment for seasonal affective disorder: a multicenter study. AB - The effectiveness of light therapy in seasonal affective disorder (SAD) was evaluated in 105 subjects across five centers. Three intensities of light (60 lux, 600 lux, and 3500 lux) were used in a 2-week randomized, parallel design. There was no significant difference in antidepressant efficacy of the three intensities of light. All three intensities produced a similar frequency of antidepressant response to each other and to that reported in previous studies. There were site differences in the severity of depression during light treatment, but diagnosis and medication status did not affect antidepressant response. These findings suggest that light therapy has an antidepressant action by a nonspecific effect or that light is biologically active in the treatment of SAD across a wide range of intensities. PMID- 8464952 TI - Effect of desipramine on cerebrospinal fluid concentrations of corticotropin releasing factor in human subjects. AB - To assess the effect of desipramine (DMI) on corticotropin-releasing-factor (CRF) activity in the central nervous system, we measured cerebrospinal fluid (CSF) concentrations of CRF in healthy volunteers following short-term administration of DMI or placebo. DMI administration for 2 days was associated with a significant dose-related reduction in CRF concentrations. There was a nonsignificant 6% reduction in CRF concentrations among the 10 subjects who received 50 mg DMI (delta CRF: -3 +/- 2 pg/ml) and a significant 14% fall in the CRF concentrations of the eight subjects who received 100 mg DMI (delta CRF: -8 +/- 3 pg/ml). The mean CSF concentration of CRF was unchanged in the six subjects randomized to placebo (delta CRF: 1 +/- 5 pg/ml). DMI administration had no effect on CSF norepinephrine concentrations (n = 24) or on plasma cortisol (n = 25). We conclude that short-term administration of DMI in healthy volunteers is associated with a dose-related reduction in CSF concentrations of CRF. PMID- 8464954 TI - Frequency of seasonal affective disorder among individuals seeking treatment at a northern Canadian mental health center. AB - The frequency of seasonal affective disorder (SAD) was examined in clients receiving treatment for recurrent mood disturbances in a northern Canadian site. Approximately one-fifth of these individuals were identified as having SAD when file histories and a statistical criterion were used as the basis for assessment. The failure to find a higher prevalence rate at this latitude may be due to other studies' reliance on client self-report, a tendency for individuals with SAD to relocate south, or a greater tendency for clients with SAD to be seen by general practitioners and alcohol treatment centers in the north. PMID- 8464955 TI - Psychosis proneness scales in schizophrenia spectrum personality disorders: familial vs. nonfamilial samples. AB - The authors evaluated the extent of overlap between DSM-III-R schizophrenia spectrum personality diagnoses (SSPD) and the Psychosis Proneness Scales of Chapman and his associates. The subjects were recruited from the family members of schizophrenic patients ("familial" subjects; n = 45) and members of the community with negative family histories for schizophrenia ("nonfamilial" subjects; n = 60). Clinical interviews were performed to obtain DSM-III-R Axis I and II diagnoses. In 105 individuals with no Axis I diagnosis, the five Chapman Scales were administered. The results suggest that the nonfamilial subjects with diagnoses of SSPD (n = 24) scored significantly higher on the Chapman Scales of Magical Ideation, Perceptual Aberration, and Impulsive Nonconformity compared with the familial SSPD subjects and the other non-SSPD groups. The familial SSPD subjects (n = 17) scored significantly higher than the nonfamilial, non-SSPD groups on the Physical Anhedonia Scale. Scores on the Social Anhedonia Scale were highest in the SSPD subjects, but only scores for the nonfamilial SSPD subjects were statistically different from those for the other non-SSPD groups. The data were reanalyzed by first dividing the scores from the Chapman Scales into high and low scores based on different cutoff points. Sensitivities, specificities, and predictive powers of the "high" Chapman scores for SSPD diagnoses were then calculated. These were done because the Chapman Scales are often used to identify individuals with schizophrenia-related personality disorders on the basis of scores that exceed arbitrary cutoff points. The results suggest that the Chapman Scales (other than the Physical Anhedonia Scale) and DSM-III-R criteria identified mostly the same subjects, when only nonfamilial subjects were considered (with sensitivities and specificities of about 0.70). However, the overlap between these two constructs was poor when only schizophrenia spectrum subjects recruited from the family members of schizophrenic patients were considered. PMID- 8464956 TI - Anxiety disorders in the joint hypermobility syndrome. AB - A case-control study was designed to test the association between joint hypermobility syndrome (JHS), an inherited disorder of collagen synthesis, and anxiety and phobic disorders. One hundred fourteen cases of JHS diagnosed at the rheumatology outpatient clinic of the Hospital del Mar (Barcelona) were compared to 59 control subjects randomly selected from patients seen at the same clinic. Both cases and controls were examined by a psychologist who used the Structured Clinical Interview for DSM-III-R and who was unaware of their medical diagnoses. DSM-III-R diagnoses of panic disorder, agoraphobia, and simple phobia, but not generalized anxiety disorder, dysthymic disorder, or major depression were found to be highly associated with JHS (age- and sex-adjusted odds ratio = 10.7). Mitral valve prolapse (MVP) was present only among JHS cases. Among cases of JHS, subjects with MVP were almost three times more likely to suffer from anxiety than subjects without MVP (odds ratio = 2.95), although the association was not statistically significant. The strong association between panic anxiety and JHS appears to occur at a higher level than the association between panic and MVP, and provides a new basis for further studies on the genetic background of panic anxiety. PMID- 8464957 TI - No evidence of linkage between schizophrenia and D3 dopamine receptor gene locus in Icelandic pedigrees. AB - The D3 dopamine receptor gene is an important candidate gene for schizophrenia, since--because of its almost exclusive expression in the limbic system--it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. Pairwise linkage analyses were carried out between the D3 dopamine receptor gene locus (DRD3) and schizophrenia (including major depression among its pleiotropic manifestations). On the basis of these analyses, which assumed a penetrance of 0.71 and a dominant mode of inheritance, we were able to exclude the DRD3 locus with a lod score of -2.50 in four Icelandic pedigrees. The area of exclusion (lod score < -2.00) extended 1.2 centimorgans. We conclude that the genetic predisposition to schizophrenia in these pedigrees is not due to a mutation in the DRD3 locus. However, these results cannot exclude the possibility that a defect in other genes regulating the expression of the D3 dopamine receptor gene could be involved in the pathogenesis of schizophrenia or that linkage analyses in other families or population-based association studies might show a positive result. PMID- 8464958 TI - Sodium lactate infusion in late luteal phase dysphoric disorder. AB - The effects of sodium lactate infusion were compared in 13 women who sought treatment for marked premenstrual dysphoric changes that met criteria for late luteal phase dysphoric disorder and 7 control women. No subject had a lifetime history of panic disorder. The rate of blindly rated panic to sodium lactate was 7 (58%) in patients and 0% in controls. Nonpanicking patients also had higher Modified Acute Panic Inventory scores than control subjects. The differences cannot be fully explained on the basis of a history of panic attacks. Further study is warranted. PMID- 8464959 TI - Decreased heart rate variability in panic disorder patients: a study of power spectral analysis of heart rate. AB - We have previously found decreased standard deviations and mean consecutive differences of R-R intervals in panic disorder patients in standing posture, compared with control subjects. In the present study, we used spectral analysis of heart rate variability to examine autonomic function in 21 panic disorder patients and 21 normal control subjects. Patients had a significantly lower standard deviation of heart rate in supine as well as standing postures. Absolute low frequency power (0.01-0.05 Hz) was also significantly lower in panic disorder patients in standing postures. Upon standing, the panic disorder patients had significantly higher relative mid-frequency power (0.07-0.15 Hz). During a standing deep-breathing condition at six breaths per minute, the patients had a significantly decreased absolute and relative mid-frequency (0.07-0.15 Hz) power compared with control subjects. These findings suggest a decrease in cholinergic and a relative increase in adrenergic responsiveness in panic disorder patients compared with control subjects. PMID- 8464960 TI - Antisocial symptoms in preadolescent boys and in their parents: associations with cortisol. AB - Conduct disorder (CD) symptom counts in preadolescent boys, and antisocial personality disorder (ASP) and childhood conduct disorder symptom counts in their parents, were used as dimensional measures of behavioral deviation. A significant correlation was found for CD and ASP symptom counts between the two parents and between CD symptom counts of the children and parental CD and ASP symptom counts. Although socioeconomic level correlated negatively with parental symptom counts, no association was observed between parental socioeconomic status and children's CD symptom counts. Saliva cortisol level in the children was negatively associated with their CD symptom count and with their fathers' ASP count. Cortisol level was also lower among sons whose fathers had CD as children and subsequently developed ASP compared with the cortisol level in sons whose fathers either did not have any Axis I psychiatric disorder or did not develop ASP. PMID- 8464961 TI - [Psychosomatic aspects of rheumatic diseases]. AB - The spectrum of rheumatic diseases includes syndromes characterized solely by musculoskeletal pain and discomfort. Indeed, muskuloskeletal pain and dysfunction are experienced by almost everyone in the course of a lifetime. The rheumatic syndromes are diverse and often of unclear etiology. For many years, psychosomatic theories have been advanced as an attempt at explanation, especially in the case of chronic polyarthritis. This article discusses the meaning of risk factors viewed as relevant to the course of back pain syndromes in particular. Therapeutic and rehabilitative-psychological interventions for comprehensive treatment of chronic rheumatic pain-patients are presented, and the necessity for a well-coordinated psychosomatic-interdisciplinary approach is emphasized. PMID- 8464962 TI - ["Burnout" and the need for psychosocial education and supervision in inpatient care of the aged]. AB - 255 staff persons in the inpatient care for elderly (mainly nursing home staff, nurses and assisting personal) were included in a multicenter questionnaire study. Main strain was reported as time pressure at work (59%), followed by organisational deficits (22%) and compassion with the suffering of some inhabitants. The analysis of influencing factors yielded only a few results, job- and occupation-related factors might increase the risk of getting "burned out" (especially qualification and responsibility taken), as well as younger age. Two risk groups with respect to "burnout" were identified by cluster analysis: a bigger group (47%) of younger staff, markedly strained, but also highly skilled and motivated ("burnout-endangered" group), and a smaller group (8%) with high strain and low job satisfaction ("burnout-group"). More than half confirmed that psychosocial staff training and supervision is important and necessary and should mainly deal with problems of team interaction and ways of emotional relieve. Training units of 90 minutes once a month was the mode mostly favoured. Main issues were aspects of interaction with problematic elderlies (especially with depressive or aggressive persons) as well as dealing with death and dying. PMID- 8464963 TI - [Coping and life satisfaction in patients with Hodgkin's disease in remission. A contribution to the question of adaptive aspects of coping processes]. AB - Widening the focus from survival time to the "quality of survival" this cross sectional study was designed to find correlations between coping strategies, quality of life, sociodemographic and medical data. 61 patients (31 women, 30 men; mean age 41 [22-74] with Hodgkin's disease receiving no treatment since 1 month to 16 years (mean 5 years) were assessed for coping and quality of life. Two standardized questionnaires were used: "Freiburg Questionnaire of Coping with Chronic Illness" (FKV 102) and "Questions for Life Satisfaction" (FLZ). Coping strategies were evaluated. The most used strategies were compliance strategies and trust in doctors. Some coping strategies correlated significantly with age, sex, marital status, education, and medical data as B symptoms and occurrence of recidivs. The scores for life satisfaction were absolutely high in comparison with postoesophagectomy patients and healthy controls from other studies. Life satisfaction was correlated with age, B symptoms and type of therapy. These correlations and correlations between FKV and FLZ were discussed and basic problems were reflected. PMID- 8464964 TI - [Collection of relevant data in psychoanalytically oriented inpatient psychotherapy--The Tiefenbrunn Documentation System]. AB - We inform about development of the Tiefenbrunn documentation system for inpatient psychotherapy. Aims and scaffolding of the system and some difficulties to make the system run are outlined. The newly developed instruments are sketched. Patients received a questionnaire concerning their social situation and their family of origin. At the same time therapists indicate symptoms, diagnosis, work ability, prognosis, pretreatments and chronification (diagnosis sheet I) and results of treatment (diagnosis sheet II) when patients leave. During treatment complementary therapy (as e.g. massage etc.) is documented. From 1988 on we have 230 variables on every patient in our computers. Actual and further use of the system is described. PMID- 8464965 TI - [Attitude, process fantasy and progress assessment after inpatient psychotherapy- the Tiefenbrunn Termination Interview]. AB - This is a preliminary study on the qualitative evaluation of inpatient psychotherapy by means of a semistandardized interview at the end of treatment. The interview focus is on the patients' attitude, fantasy of cure and view of achieved progress. These components are formulated in a metaphoric, every-day language which are set in relation to the patient's quantitative evaluation of treatment. Experience of therapy appears as consistently embedded in, and depending from the patient's lay theory of cure, which also determines his measure of outcome. Obviously, an important dimension of psychotherapeutic interaction can be described as "negotiating" the lay theory of cure. PMID- 8464966 TI - [Crohn disease--addiction--neurosis: comparison of ego functions]. AB - 25 neurotic patients, 25 alcoholics, and 25 patients suffering from Crohn's disease were rated with a german adaption (by Streeck) of Bellak's Ego Function Assessment scales. Crohn's disease patients showed personality characteristics similar to those of patients suffering from psychosomatic illnesses. Ego function disturbances could be found with respect to Introspection as a subfunction of Reality Testing, Creativity and Capacity for Abstraction as a subfunction of Thought Processes. The results indicated a remarkable heterogeneity of the Crohn's-patient group as well as possible influences of gender-specific personality differences in that group. PMID- 8464967 TI - [Interpersonal problems, interpersonal orientation and success of treatment after inpatient group psychotherapy]. AB - To describe and estimate the importance of interpersonal problems and orientations for inpatient group psychotherapy, a total of 78 inpatients from two different hospitals (university hospital Kiel, psychotherapeutic hospital Berlin Hirschgarten) were investigated using the Inventory of Interpersonal Problems and the SCL90R prior to and (partly) following longterm psychotherapy. Both groups reported more interpersonal problems than a group of 55 outpatients. The subgroups differed from each other in terms of their symptoms reported in the SCL90R and their interpersonal orientation (sensu Horowitz) which was smaller in the patient group from the Berlin Hospital (an institution of the former German Democratic Republic). Within this subgroup, treatment success (obtained with a variety of different measures) appeared to be less in those patients whose interpersonal problems were mainly related to the dimension of dominance. The ratio of interpersonal to impersonal problems was not significantly related to therapy outcome in either of the subgroups. The results of this study are mainly discussed with respect to the different psychotherapeutic concepts practiced in both hospitals. Generally, the investigation supported the significance of the interpersonal dimension for empirical research within the field of inpatient psychotherapy. PMID- 8464968 TI - [Situational anxiety in myasthenia gravis]. AB - Neuromuscular block can cause anxiety. These known experimental results lead to the expectation of conditioned phobic reactions in myasthenia gravis. A sample of 240 patients with the disease do not show the theoretically expected results in the Fear-Survey-Schedule. But interindividual variation of anxiety corresponds to some clinical parameters, relevant for the disease. Patients with facial muscular symptoms have higher values on social phobia but no higher scores on a depression scale. Opposite to the facial-feedback theory, this result supports the hypothesis, that intersubjective feedback is more significant to the development of the emotional reaction than proprioceptive (facial) feedback. Social anxiety also covariates with defensive coping-strategies. Implications for supportive psycho(behaviour)therapy are discussed. PMID- 8464969 TI - Health promotion and disease prevention--10 years of student inventiveness. PMID- 8464970 TI - Breast self-examination for visually impaired women. AB - Regularly practiced breast self-examination (BSE) has been demonstrated to be an effective method in the early detection of breast abnormalities. Women are becoming increasingly aware of the importance of BSE as a means of self-health care and are seeking instruction on how to perform such examinations properly. Unfortunately, not all women have equal access to BSE instruction. This project addresses the need for BSE instruction specifically tailored to meet the needs of visually impaired women. A review of existing sources revealed that no formal methods of BSE instruction are being used to meet the needs of this population. The participants in this study included 20 women between the ages of 30 and 75 years, all of whom are partially sighted or legally blind. The women participate in life skills classes on a regular basis at a county association for the blind. The authors conducted an instructional seminar demonstrating BSE and used methods which focus on the senses of touch and hearing. According to the authors, the instructional seminar can result in an increased self-awareness of the importance of BSE and help to meet the unique needs of the visually impaired women. PMID- 8464971 TI - Teen Peer Outreach-Street Work Project: HIV prevention education for runaway and homeless youth. AB - Each year, there are approximately 2 million homeless and runaway youths in the United States. On any given night, there are 1,000 homeless youngsters living on the streets of San Diego, CA. Homeless young people are commonly involved in one or more of the following activities that place them at risk for HIV infection- unprotected sexual intercourse, needle-sharing in the use of injectable drugs, sex with someone who injects drugs. The Teen Peer Outreach-Street Work Project trains teen peer educators to work in three existing San Diego youth service programs with street outreach staff members to provide HIV prevention education and referral services to San Diego's homeless youth. Selected teens from the target population also participate in street-based case management that provides skill development to bring about behavioral and attitudinal changes. An HIV outreach program cannot stand alone and is most successful if it is integrated with services that meet the basic needs of its clients. In the three participating youth service programs of the Teen Peer Outreach-Street Work Project, food, clothes, and shelter information are provided. There are shelters in two of the three programs that become places where HIV educational messages, delivered on the street, can be reinforced. Immediate and concrete assistance can be offered to homeless youth. Low literacy among the target population presents a significant obstacle to adequate and appropriate HIV prevention education for homeless youth. Currently, education materials that specifically target homeless youth do not exit. The outreach street project is being expanded to develop materials for homeless youth with low literacy levels. Teen peers will be used to facilitate structured focus groups composed of members of the target population. Focus groups will be used in concept development, product development, and evaluation of draft products.Because the project is unique.in San Diego, it addresses an unmet need, reaching a population often missed by traditional HIV education efforts. PMID- 8464972 TI - Cervical cancer prevention project for inner city black and Latina women. AB - Early detection, appropriate intervention, and adequate followup treatment make cervical cancer one of the most preventable of all diseases. The authors propose a project designed to increase knowledge and awareness of cervical cancer and its prevention and ultimately to decrease morbidity and mortality rates for cervical cancer in black and Latino inner-city communities of Boston. During a 3-year project the authors hope to reach about 500 high-risk women who currently do not have access to health care services. The interventions would be based in the Boston, MA, community areas of Roxbury and Jamaica Plain, specifically in those neighborhoods served by a designated community health center. High rates of cervical cancer are found in inner-city communities, where black and Latina women usually are overrepresented. About 80 percent of the women served by the designated community health center are either black or Latina. The proposed intervention has three objectives: (a) to increase the use of health services by so-called hard-to-reach women in those communities; (b) to reduce the numbers of women who, after learning of their abnormal Papanicolaou test results, do not return for followup; and (c) to increase sensitivities toward the problem and to encourage participation in such a project among health care providers at the community health center. PMID- 8464973 TI - Model prenatal program of Rush Medical College at St. Basil's Free Peoples Clinic, Chicago. AB - The lack of adequate prenatal and gynecological care for indigent women has reached crisis proportions. The situation is aggravated by the diminishing supply of primary care physicians who are willing to practice obstetrics in community settings. Added to this condition is the rapidly declining number of medical students seeking careers in the primary care field. The Rush Prenatal Program at St. Basil's Free Peoples Clinic on Chicago's south side addresses these problems by (a) delivering comprehensive prenatal care to poor and disadvantaged women; (b) providing a learning environment in which medical students are taught to be humane, culturally sensitive, and competent physicians through active involvement in patient management; and (c) creating an experience that reinforces the student's self-motivation to practice community-oriented primary care. At the clinic 24 medical students, working in teams supervised by the three program physicians, maintain continuity of excellent prenatal care that follows the expectant mother from pregnancy through delivery and beyond. The Rush Prenatal Program, which has been initiated, organized, and managed by medical students, has evolved into a model of education and service that can be emulated at other institutions. All participants in the program--students, faculty, patients, and community representatives--are being followed longitudinally as a method of assessing program efficacy. This collaborative effort between an academic medical center and a neighborhood clinic demonstrates that such a partnership is not only feasible but potentially cost effective and socially responsible. PMID- 8464974 TI - The psychological consequences of the Chernobyl accident--findings from the International Atomic Energy Agency Study. AB - In October 1989, more than 3 years after the nuclear power plant accident at Chernobyl, in the Ukraine, the Government of the Union of Soviet Socialist Republics requested that the International Atomic Energy Agency (IAEA) evaluate the medical and psychological health of residents living in areas identified as being contaminated with radioactive fallout. The IAEA designed and conducted a collaborative study to examine whether there were any measurable effects of exposure to the low levels of ionizing radiation resulting from the accident. The study, using structured interviews and IAEA laboratory equipment, collected data on more than 1,350 residents of 13 villages. IAEA clinical staff members concluded that they could not identify any health disorders in either the contaminated or nearby (uncontaminated) control villages that could be attributed directly to radiation exposure. The clinical staff, however, did note that the levels of anxiety and stress of the villagers appeared to be disproportionate to the biological significance of the levels of IAEA-measured radio-active contamination. Almost half the adults in all the villages were unsure if they had a radiation-related illness. More than 70 percent of persons in the contaminated villages wanted to move away, and approximately 83 percent believed that the government should relocate them. The IAEA effort indicates that the villagers need to be educated about their actual risks, and they need to understand what types of illnesses are, and are not, associated with exposure to radioactive contamination. Unfortunately, the villagers' needs may exceed the available resources of their local and central governments. PMID- 8464975 TI - Cirrhosis hospitalization and mortality trends, 1970-87. AB - The decline in cirrhosis mortality in recent years in light of increases in cirrhosis morbidity, as reflected in hospital discharge data, is examined. Although there does not appear to be a single explanation for the decline in mortality, it is suggested that increased identification and treatment, as measured by substantial increases in the rates of hospitalization involving cirrhosis, may be a contributing factor. If, as suggested by hospitalization data that indicate a decreasing proportion of patients with cirrhosis die during their hospital stay, a major portion of the increase in cirrhosis admissions was for patients with less severe cases, these patients would be more responsive to treatment and would have a relatively better prognosis. The identification of contributing factors that may be responsible for the decline in cirrhosis mortality can provide support for the continuation of early diagnosis and treatment in already identified populations. The same kind of support can be extended to other population subgroups that have yet to show the same decline in cirrhosis mortality. PMID- 8464976 TI - Assessing the public's health: community diagnosis in North Carolina. AB - The community diagnosis process in North Carolina has evolved over a period of years. It began in 1974 and gained great impetus during and after 1983. It serves to address the "true" health problems of the State's citizenry through the identification and communication of these problems from the local level to the State. In this "bottom-up" planning process, conducted biennially, the State health department prepares 100 county-specific health data books and an accompanying guide that advise local health department personnel on the concepts, methods, and materials of community diagnosis. The data books and guides are presented at a series of workshops to county health department personnel who subsequently analyze the data in the light of their local situations and report back to the State their county's priority health problems and strategies for solving them. This county information is then used by the State health director to determine funding requests to the legislature. In the end, it is hoped that the products of this process serve the ultimate goal of allocating resources according to priorities to meet the documented health needs of North Carolinians. "The Future of Public Health," authored by a committee of the Institute of Medicine, defines a health planning and leadership role for a local health authority that is fundamental to the protection of the community's health. Community diagnosis provides for the kind of needs assessment that is crucial to that role. PMID- 8464977 TI - A cost-benefit analysis of a California county's back injury prevention program. AB - Back-related injuries have become a major health problem in the workplace, affecting as many as 35 percent of the work force and accounting for about 25 percent of all compensation claims. This study evaluates a back injury prevention program among employees in a northern California county in 1989-90. Six divisions of the county government were selected for the study because they had the highest prevalence of back pain experienced and the most back-related injuries in recent years. Four of the six divisions were randomly selected as the intervention group and the remaining two, the control group. Overall, 77 percent or 205 of the targeted employees in the intervention group participated in the study. The intervention group was given an identical health risk assessment (HRA) before and after the 1-year back injury prevention program that offered employees a combination of education, training, physical fitness activities, and ergonomic improvement. The control group was neither given the HRA nor offered the program. The back injury and cost data of both the control and intervention groups were collected before and after the 1-year intervention. The results showed a modest overall decline in back pain prevalence rates, but significant improvement in satisfaction and reduction in risky behaviors. Cost-benefit analysis showed the net benefit of introducing back injury prevention program was $161,108, and the return on investment is 179 percent. Therefore, the study offers suggestive evidence for the initial benefits of a back injury prevention program and lends support to the widely held belief that health promotion in the workplace can reduce employee health risks, increase healthful behaviors and attitudes, and improve attitudes toward the employer organization.Whether such intervention will continue to reap benefits in future years depends, to a large extent,on a favorable work environment and the maintenance and continuation of positive behavioral changes. PMID- 8464979 TI - Smoking behavior of adolescents exposed to cigarette advertising. AB - The purpose of the study was to explore the relationship between the exposure of adolescents in the seventh and eighth grades to cigarette advertising and their being smokers. A survey questionnaire given to 602 adolescents assessed their exposure to cigarette advertising and provided measures of their smoking behavior, demographic characteristics, and some psychosocial variables. The results indicated that exposure to cigarette advertising and having friends who smoked were predictive of current smoking status. Adolescents with high exposure to cigarette advertising were significantly more likely to be smokers, according to several measures of smoking behavior, than were those with low exposure to cigarette advertising. The findings extend previous research identifying factors that may play a role in the initiation and maintenance of smoking among adolescents. PMID- 8464978 TI - Bicycle helmet use by adults: the impact of companionship. AB - Most of the nearly 1,000 fatal bicycle-related injuries annually could be prevented if riders used safety helmets. Helmet use by adult bicyclists has received relatively little attention because educational campaigns to promote helmet use generally focus on children. Helmet use by adult and child bicyclists at 120 suburban and rural sites in three Maryland counties was observed on two Saturdays in 1990-91 during an evaluation of the impact of a mandatory helmet law. Concordance or discordance of helmet use within various groups of bicyclists -adults only, adults with children, and children only--was recorded. Helmet use among 2,068 adult bicyclists was 49 percent, 51 percent, and 74 percent in the three counties. In two counties combined, 52 percent (365 of 706) of solo adult bicyclists wore helmets compared with only 5 percent (5 of 94) of solo child bicyclists (P < .001). Helmet use or nonuse was concordant among 87 percent of 277 adult-adult pairs, 94 percent of 50 child-child pairs, and 91 percent of 32 adult-child pairs of bicyclists observed. Concordance rates of helmet use or nonuse were similarly high among pairs of adult bicyclists of the same or mixed sexes. These data are consistent with the concept that both adults and children tend to adopt the helmet-wearing behaviors of their companions. Public health efforts focused on adults should encourage helmet use by adult bicyclists both to prevent head injuries and to provide a role model for children. PMID- 8464980 TI - A fetal alcohol syndrome surveillance pilot project in American Indian communities in the Northern Plains. AB - A pilot fetal alcohol syndrome (FAS) surveillance was carried out in four American Indian communities in the Northern Plains by the Aberdeen Area Indian Health Service to determine the incidence of FAS and to evaluate the feasibility of establishing continuing surveillance for FAS. Baseline data on the incidence of FAS would be used by the Indian Health Service to develop and evaluate preventive interventions, including treatment programs for pregnant women who drink alcohol. Four of the 1,022 children included in the project were found to have FAS, a rate of 3.9 per 1,000 live births. The rate is believed to underestimate the true rate of FAS because some low birth weight children were not screened, parents or guardians were reluctant to bring children suspected of FAS for evaluation, clinicians were hesitant to diagnose possible alcohol-damaged children for fear of labeling the child, and some children with FAS died before the diagnosis of FAS could be confirmed. If the rate of FAS is similar for the 39 percent of the infants not screened and for the 25 percent of suspected infants who were not evaluated, a rate of 8.5 cases of FAS per 1,000 live births may be postulated. The authors recommend routine screening of prenatal patients for substance abuse and establishing a tracking system for low birth weight infants suspected to have FAS or other alcohol-related developmental disorders, in an effort to establish more accurate FAS rates. Such a surveillance system would identify women at risk of having alcohol-affected infants so that appropriate treatment and counseling could be provided, possibly reducing the severity of adverse effects of alcohol on their fetuses. PMID- 8464981 TI - Development of the New York State Nutrition Surveillance Program. AB - New York State established a Nutrition Surveillance Program (NSP) in 1984. Precedents for the program included the Pediatric Nutrition Surveillance System of the Public Health Service's Centers for Disease Control and Prevention and periodic food and nutrition surveys conducted by the National Center for Health Statistics and the Human Nutrition Information Service, Department of Agriculture. The first phase of NSP was connected to a new program, the Supplemental Nutrition Assistance Program (SNAP), which established support for more than 1,000 emergency food programs across the State. SNAP also expanded the home delivered meal program for the frail elderly and the Special Supplemental Food Program for Women, Infants, and Children. NSP provided information on the extent of unmet nutrition needs that was used to establish funding requests and provided data describing the characteristics of SNAP participants that were used in developing new SNAP program components. The second phase of NSP began in 1988. It identified populations that were thought to be at nutrition risk and compiled information about the extent of unmet need, the characteristics of the population, and the status of current nutrition programs to meet the needs. As a result of this review, NSP added a nutrition component to the Dental Survey of School Children; conducted a dietary survey; developed an inventory of information sources in all State agencies; and established an annual work plan using department of health objectives. The third phase of NSP is the policy and planning phase, monitoring the Year 2000 Objectives and the Five-Year Plan of the New York State Food and Nutrition Policy Council. PMID- 8464982 TI - The Public Health Service's response to Hurricane Andrew. PMID- 8464983 TI - Elderly persons' attitudes towards footwear--a factor in preventing falls. AB - Injuries from falls are the main cause of trauma morbidity that leads to mortality among the elderly. One prevention strategy is to wear sturdy shoes. This study was undertaken to determine the attitudes towards and use of sturdy shoes among older adults. A random sample of persons ages 65 years and older was contacted by phone; 652 completed interviews. Sturdy shoes were worn by 26 percent of persons at the time of the call; more than two-thirds reported wearing such shoes at some time. Barriers to use of sturdy shoes included foot problems, difficulty putting them on, expense, style, and lack of knowledge about their importance. There was no difference in shoe use by the respondents' history of previous falls. The results provide information useful in the development of a program to increase the use of sturdy shoes by this population. PMID- 8464984 TI - Study of road-rail crashes in Claremore, OK, and allocation of resources for preventive measures. AB - Road-rail crossings where a train and motor vehicle crashed were compared with the next crossing in the direction from which the train traveled at the same time of day and day of week of the crash. The odds of a crash were much lower at crossings with automatically lowered gates (odds ratio = 0.11). Average road traffic was much higher at crash sites; the presence of automatic gates was unrelated to the volume of road traffic. Federally funded modifications of road rail crossings have substantially reduced deaths at such sites. The program would be more cost effective, however, if criteria for highest risk sites were applied more systematically, and funds were apportioned among the States according to their relative proportions of the problem. PMID- 8464985 TI - FDA warns frequent yeast infections could be early sign of HIV. PMID- 8464986 TI - Antibodies to gangliosides in Guillain-Barre syndrome: specificity and relationship to clinical features. AB - Antibodies to ganglioside GM1 have been associated with Guillain-Barre syndrome. To clarify their role we have studied their frequency, fine specificity and relationship to clinical features in a series of patients with this disease. Antibodies to ganglioside GM1 were identified, by both enzyme-linked immunosorbent assay and binding to thin-layer chromatograms of human brain, in 12 (28.6%) of 42 patients with Guillain-Barre syndrome and in only 1 (2.4%) of 41 normal control subjects (p = 0.002). Eight sera contained IgM antibodies and six sera contained IgG antibodies, including 2 sera which contained both. The fine specificity of the sera varied. Only four of the 12 sera also showed reactivity with ganglioside GD1b and gangliotetraosyl-ceramide (asialo-GM1), consistent with reactivity with the terminal Gal beta 1-3GalNAc disaccharide. Two sera had low titre anti-asialo-GM1 antibodies of a different class to the anti-ganglioside GM1 antibodies. The antibodies in these sera therefore react with a variety of epitopes. There was a strong relationship between the presence of anti ganglioside GM1 antibodies in the acute stage and prolonged disability, especially if IgG antibodies were present. Seven of 12 patients with anti ganglioside GM1 antibodies had serological evidence of recent Campylobacter jejuni infection, but antigens from a strain of this bacterium not associated with Guillain-Barre syndrome did not absorb the anti-ganglioside GM1 antibodies. PMID- 8464987 TI - Clinical, biochemical and histological features in 102 patients with chronic hepatitis C virus infection. AB - The clinical, biochemical and histological features of 102 consecutively referred patients with chronic hepatitis C virus infection were analysed. Demographic, epidemiological, biochemical, haematological and histological details were catalogued for each patient. The mean follow-up was 49 +/- 6 months. Liver biopsies were obtained from 92 patients; a second biopsy was obtained from 35 patients. The average known duration of infection was 8.6 +/- 0.7 years. The most common risk factors that could be identified were past blood transfusion, surgery or intravenous drug abuse. Twenty-four of the 27 patients (85%) with past blood transfusion had received blood in countries outside of northern Europe. In contrast, 12 of the 16 former drug users were northern European. Patients were frequently diagnosed incidentally; one-quarter had no symptoms of liver disease and were generally asymptomatic or had presented with non-specific complaints and were found to have abnormal serum aminotransferase levels after routine screening. The mean serum aminotransferase levels were not significantly different in those presenting with fatigue compared to those diagnosed incidentally. The most common physical sign in these patients was a palpable liver, which was present in 52%. The mean serum albumin concentration in patients older than 40 years was significantly lower than that in younger patients. Splenomegaly and endoscopic evidence of varices was also more common in older patients. Cirrhosis was present in 37% of patients at presentation: 20% showed progression on rebiopsy, and 5% developed cirrhosis within 4 years of initial presentation. Of those treated, 27% showed histological improvement. Histological severity did not correlate with duration of disease, but did correlate with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8464988 TI - Reversible hypocalciuria with marginal hypercalcaemia in renal magnesium wasting. AB - Low urinary calcium levels and hypomagnesaemia were observed in three subjects with renal tubular abnormalities. The first, with severe hypomagnesaemia due to congenital renal magnesium wasting, had mildly raised serum ionized calcium levels (1.34-1.36 mmol/l). The other two, a brother and sister, had features of Bartter's syndrome with hypokalaemia, mild hypomagnesaemia and hyperreninaemia with normal serum ionized calcium levels. Hypocalciuria was seen in 24-h urine collections and in 2-hourly timed urine collections. Magnesium loading with intramuscular MgSO4 was used to raise serum Mg to within the normal range. Tubular reabsorption of Mg (TMg) rose while TCa fell, with a rise in fractional excretion of ionized Ca and a small drop in serum ionized Ca. Serum parathyroid hormone levels rose or remained constant. This pattern is consistent with a shared Ca/Mg reabsorptive pathway with a rise in TCa when TMg is low, returning to normal when TMg is raised by Mg loading. In one subject, this imbalance was associated with marginal hypercalcaemia. The site for this pathway is likely to be the thick ascending limb of the loop of Henle. PMID- 8464989 TI - Anti-reticulin antibody in gluten sensitive enteropathy. PMID- 8464990 TI - Hypogammaglobulinaemia and replacement therapy. PMID- 8464992 TI - DNA diagnosis: PCR on archival tissue. PMID- 8464991 TI - Patient self-referral in acute myocardial infarction. PMID- 8464993 TI - ANCA-associated renal disease. PMID- 8464994 TI - Renal replacement therapy on the intensive care unit. PMID- 8464995 TI - Lipids and cardiovascular disease: ephemeral and elusive receptors. PMID- 8464996 TI - Acute renal failure treated by haemofiltration: factors affecting outcome. AB - Two hundred and fifty consecutive patients with acute renal failure treated by continuous haemofiltration on one intensive care unit (ICU) were studied prospectively to investigate the possibility of predicting outcome at the time of referral. Logistic regression analysis was used to identify important prognostic factors and the regression coefficients were used to weight a scoring system for the severity of illness of patients with acute renal failure. Overall survival was 53% with improvement over the course of the study. Multivariate analysis showed that outcome was related to age, need for artificial ventilation, use of inotropes, urine volume, serum bilirubin, arterial base deficit and serum creatinine. The scoring system based on the first five of these variables had a specificity of predicting death of 67% and a sensitivity of 76%. PMID- 8464997 TI - Acid-base status in paediatric Plasmodium falciparum malaria. AB - We measured the acid-base status of children with falciparum malaria in order to determine the prognostic significance and rate of resolution of acidaemia in patients with severe disease. We prospectively studied 141 Malawian children who were admitted to Hospital, with falciparum malaria, 60 of whom had cerebral malaria (unrousable coma, unable to localize a painful stimulus). Of the 60 patients with cerebral malaria 25 (42%) were acidaemic (capillary blood pH < 7.3); of 81 children with uncomplicated malaria 4 (5%) were acidaemic (p < 0.0001). Eleven patients died; of these, eight presented with cerebral malaria, eight with acidaemia and seven with both. The strong association of altered acid base status with disease severity and mortality was independent of other previously identified predictors of illness and death in malaria. Acidaemia was not associated with shock, bacteraemia or hypoxaemia. Acidaemic patients had a slower mean respiratory rate and a higher incidence of respiratory rhythm abnormalities than other patients, suggesting that acidaemia is in part the result of inadequate respiratory compensation for metabolic acidosis. Although acidaemia is quickly corrected by fluids and antimalarial drugs, specific therapy to correct acidaemia needs evaluation in children with severe malaria. PMID- 8464998 TI - Molybdenum/aluminum filters perform effectively. AB - In this study, the performances of stacked niobium/aluminum and molybdenum/aluminum filters were compared to that of a standard 2.5 mm aluminum filter. The molybdenum/aluminum filter had the same performance characteristics as the niobium/aluminum filter but was less expensive. The study results show that the molybdenum/aluminum filter should be a good filter choice for facilities embracing ALARA principles. PMID- 8464999 TI - Student meetings can enhance learning. AB - This article shows how competency-based clinical education may be enhanced by scheduled clinical meetings designed to clarify and intensify the educational experience. Incorporating these meetings into the clinical education component allows flexibility and creativity in delivering quality clinical experiences. Meeting with students on a regular basis also helps distinguish between students and staff and provides faculty members the opportunity to remain current in topics outside their areas of expertise. PMID- 8465000 TI - Minority students benefit from mentoring programs. AB - Mentoring has been proposed as one strategy to attract minority students to the radiologic sciences profession. This case study describes a minority mentoring program conducted for pre-radiologic science students at a Midwestern university during the 1991-92 academic year. Ten minority radiologic science students enrolled in the mentoring program. The study showed that mentoring may be a viable option to serve the special needs of minorities for recruitment and retention. PMID- 8465001 TI - Gender-related biases in admission decisions. AB - This study tested the effects of applicant gender and attractiveness on admission ratings, personality attributions and causal attributions in the student admission decision-making process in allied health education. The study showed that although gender stereotypes are very strong, they did not affect admission ratings. However, the study did reveal that attractive candidates received higher admission ratings than unattractive applicants and the past successes of attractive applicants were more likely attributed to internal causes while the past successes of unattractive applicants were more often attributed to external causes. PMID- 8465002 TI - Outcomes assessment is vital to educators. PMID- 8465003 TI - Food irradiation: green eggs and ham? PMID- 8465004 TI - At the foot of Kilimanjaro. PMID- 8465005 TI - Your patient deserves no less than the best. PMID- 8465006 TI - The ARRT's disciplinary process. PMID- 8465007 TI - [The dead mother]. AB - This study is not concerned, as the title might suggest, with the actual death of the mother but with the child's experience of a mother who is physically present but internally absent due to depression. The child simultaneously introjects and splits off the mother imago, making mourning and "burial" equally impossible. The consequence of this cathectic deprivation is what the author calls "psychic holes" or "white depression". Green attributes to the dead mother a similar structuring function for the psychic apparatus to that attributed to the dead father in Freud's Totem and Taboo, and places the dead mother complex side by side with the Oedipus complex. PMID- 8465008 TI - [The dispute between searching and healing in psychoanalysis]. AB - In the age-old dispute as to whether psychoanalysis is a science or belongs rather to the humanities, the author favours a scientific stance. He sees interpretation in the analytic situation as providing scope for reasoned hypotheses which can be validated by empirical examination. In terms of interpretive technique this implies that interpretations must not only be framed in brief and simple terms but also in such a way as to lend themselves less to the verification of theoretical psychoanalytic truths than to the clarification of the truth specific to the given dyadic constellation. Etchegoyen claims that it is then possible for the analysand to confirm or refute an interpretation by the analyst. A successful interpretation, where the analysand finds the hypothesis convincing, is both a scientific discovery and a healing factor. PMID- 8465009 TI - [Organ worlds: basic principles of analytic body psychology]. AB - In this article, the author introduces the expression organ fantasies, pathological zones in the body self and organ world with the intention of formulating an analytical psychology of the body. He presents the view that a person's own body has the significance of a primary object which, under normal circumstances, enables a person to make several important basic experiences, such as the experience of being alive, of having a body, and of being separate from others. On the basis of this work with borderline patients, the author demonstrates that the pathological zones in the body self can be understood by means of a phase model and that the illness-producing effect of a pathological organ world is related to a defective symbolization of experiences. The author suspects that the analytical psychology of the body can be applied to psychosomatic illness as well. PMID- 8465010 TI - Adjuvant radiation therapy versus surgery alone in operable breast cancer: long term follow-up of a randomized clinical trial. AB - This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference-corresponding to a 16% reduction of deaths-in favor of the irradiated patients which, however, was not statistically significant (p = 0.09). Among those 169 patients who developed locoregional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p < 0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients. PMID- 8465011 TI - Dose-fractionation sensitivity of mouse kidney clonogens measured using different interfraction intervals and postirradiation assay times. AB - The fractionation sensitivity of kidney clonogenic epithelial cells (X irradiation in vivo, assay in vitro) was quantified using the linear-quadratic model. The cells were assayed either immediately after the fractionation schedule or after a time delay in order to compare the relative amounts of dose sparing due to fractionation (conventionally sublethal damage repair) and to post irradiation delay intervals before assay (conventionally potentially-lethal damage repair). As the delay before assay was increased, there was a tendency for both alpha and beta to decrease, and as a consequence the alpha/beta ratio stayed virtually unchanged (3.3-4.4 Gy) regardless of delay time before assay. No change in survival was observed from 12 h to 6 weeks after neutron irradiation (62 MeVp- >Be), suggesting that the change observed after X-rays was due to repair rather than repopulation. As the interfraction intervals in an 8-fraction X-irradiation schedule were increased in steps from 6 h to 5 days, there was improved survival, consistent with the presence of long-term repair. These studies provide further evidence for the potential importance of long-term repair in late reacting tissues not only during but also after multifraction irradiation schedules. PMID- 8465012 TI - Multiple primary tumours in patients treated with radiotherapy for breast cancer. AB - Between January 1954 and March 1964, 3926 patients with primary breast cancer were referred to The Department of Clinical Oncology, Edinburgh. One hundred and eighty patients developed 195 malignancies subsequent to the treatment of their initial breast cancer. Overall, the total number of second tumours was not significantly in excess of the expected incidence in the general population. However, statistical analysis revealed a significant increase in the incidence of rectal, skin and bone tumours. The excess of bone tumours was likely due to radiation exposure. There was not an overall excess of tumours within the irradiated or scattered radiation volume. PMID- 8465013 TI - Re-irradiation tolerance in the rat spinal cord: influence of level of initial damage. AB - The influence of the level of initial radiation damage on the long term recovery and re-irradiation tolerance in the rat spinal cord was investigated. Rats were irradiated with 0, 10, 20, 30 and 36 daily fractions of 2.15 Gy initially representing 0, 25, 50, 75 and 90% of cord tolerance. After an interval of 20 weeks, retreatments were given using graded single doses of X-ray. The end-point was paralysis of the forelimbs due to white matter necrosis. Latent times to paralysis were inversely proportional to the level of initial injury and retreatment doses. The retreatment ED50S were 19.0, 17.0, 15.7, 14.0 and 11.8 Gy for the control animals and animals irradiated initially with 10, 20, 30 and 36 fractions of 2.15 Gy respectively. Using the extrapolated response dose (ERD) concept, alpha/beta of 3.0 Gy, the retreatment ED50S in % ERD were 81, 70, 58 and 42% after initial doses of 25, 50, 75 and 90% ERD respectively. The level of initial injury appeared to influence the proportion of residual injury. For an initial injury of 25 and 90% of ERD, the respective residual injury was 74 and 65% of the initial damage; for an initial injury of 50 and 75% ERD, the residual injury decreased to 59 and 57% respectively. It is concluded that there was significant long-term recovery in the rat spinal cord, and that the level of initial radiation damage influenced both the retreatment tolerance and the time to expression of injury. PMID- 8465014 TI - Neutron capture imaging of 10B in tissue specimens. AB - Boron Neutron Capture Therapy (BNCT) is an attractive concept for radiation treatment of malignant tumours. The patients receive a 10B-carrying compound with selective uptake in tumour cells, after which they are irradiated with epithermal neutrons. Theoretically, the tumour cells are killed by the high-LET particles produces in 10B(n, alpha)7Li reactions inside or close to the cell nucleus, while healthy brain cells with no boron uptake will be spared. In practice, a successful BNCT depends on the actual boron-distribution in the tissue, and consequently a new boron-compound aimed for BNCT must undergo detailed bio distribution studies before clinical trials. In experimental work there is accordingly a great need for methods for quantitative bio-distribution measurements in tissue samples. In this paper we present an improved technique for neutron activated autoradiography providing quantitative boron images of freeze-sectioned tissue specimens from highly malignant rat brain gliomas. Particular attention has been paid to the correlation with the morphology of the specimens and to the altered self-absorption properties due to freeze-drying. A self-absorption correction factor for tumour tissue has been experimentally determined. PMID- 8465015 TI - Treatment charts in radiation therapy. An analysis of European treatment records. AB - The radiotherapy treatment chart (dose prescription, set-up parameters, dose computation and daily dose recording form) represents an important working tool in radiotherapy, not only as a compilation of data, but also as a method of communication among physicians, physicists and technicians. In addition to administrative and medical data, physical and simulation data that are indispensable for the daily accurate reproduction of the therapy procedures should be recorded, as well as accurate daily entries of the fractional and cumulative absorbed doses. Moreover, any radiation therapy quality assurance programme must rely on the accessibility of the radiation treatment history and a correct record of the therapy protocol in order to be verifiable. We have analysed the treatment charts of 92 European Departments of Radiation Oncology, with the aim of identifying their salient characteristics and data recorded. The study shows strong differences among the charts analysed, not only in the amount of information recorded, but also in the kind of data and concepts used. PMID- 8465016 TI - Clinical thermoluminescence dosimetry: how do expectations and results compare? AB - Thermoluminescence dosimetry (TLD) for radiotherapy treatment verification is performed in the Prince of Wales Hospital in Sydney for a wide range of applications: (A) to determine the dose in difficult treatment geometries, (B) to record the dose to critical organs, and (C) to monitor special treatments such as total body irradiation (TBI). TLD measurements were performed with the aim to investigate cases where dose prediction is difficult and not as part of a routine verification procedure. We reviewed 1058 reports of TLD performed during the treatment of 502 patients between 1986 and 1991 to evaluate how the TLD results compare with the dose determined by the treatment plan. Reasons for possible discrepancies should be identified. In 19% of all investigated cases a discrepancy of more than 10% was found between expected and measured doses. The discrepancies could be divided into three groups: (1) errors made in the TLD determination or evaluation, such as placement errors of the TLD chips (21% of all discrepancies); (2) mistakes made during the patient set-up, such as insufficient shielding or inadequate patient immobilisation (30%); (3) inadequate treatment planning and dose calculation procedure, such as wrong inverse square law corrections or errors due to limitations of the two-dimensional treatment planning system used (41% of all). In 8% of all discrepancies the reason remained unclear. A number of changes to treatment plans and modalities (e.g. changed scrotal shield, modified bolus) were introduced due to TLD results. The increasing number of TLD requests per year attests to the value of TLD as a treatment verification method in clinical practice. PMID- 8465017 TI - Time trend of patient setup deviations during pelvic irradiation using electronic portal imaging. AB - An electronic portal imaging device (EPID) was used to detect patient setup displacement during the course of a 3-field pelvic irradiation of two groups of patients: 10 rectal and 10 prostate carcinomas. These patients were irradiated with conventional treatment techniques in routine clinical practice. A total of 469 portal images and 60 simulator films were used to determine the values of setup deviations in the X- Y- and Z-directions of a fixed coordinate system, corresponding to the medio-lateral, cranio-caudal and antero-posterior direction, respectively. The absolute displacement averaged over all setups and patients ranged between 0.4 mm and 1.4 mm with a standard deviation (S.D.) of 1.6-3.9 mm. The overall distribution along each direction could be separated into a distribution of random deviations (S.D.s ranging from 1.2 to 2.8 mm) around the mean deviation of each patient and a distribution of the means themselves: the distribution of systematic deviations (S.D.s ranging from 1.0 to 2.6 mm). Significant gradual displacement as a function of time was detected in 5 out of the 20 patients, 2 in the rectum and 3 in the prostate group. This "time trend" was found along each of the 3 directions specified. The magnitude of the time dependent displacement throughout the course of treatment ranged between 4 and 11 mm. It can be concluded that for treatments requiring a high level of precision, portal images should be made and analyzed during the whole treatment course in order to detect and correct significant time trends. PMID- 8465018 TI - Sizes and sources of field placement error in routine irradiation for prostate cancer. AB - Discrepancies between prescribed and treated field edges have been measured from 76 film pairs taken on 29 patients being treated for prostate cancer. The distribution of field edge discrepancies is described by a standard deviation of 4.5 mm and has an average absolute value of 3.5 mm. The observed discrepancies are shown to be attributable to field position errors and hence, in principle, are easily rectifiable. PMID- 8465019 TI - Suppressive effect of low dose total body irradiation on lung metastasis: dose dependency and effective period. AB - The dose dependency and effective period of suppressive effects by low dose total body irradiation (TBI) in both artificial and spontaneous lung metastasis were investigated using murine squamous cell carcinoma. In the artificial lung metastasis of the tumour cells injected through a tail vein, the TBI of 0.15-0.20 Gy resulted in significant net suppression of lung colony formation. With this dose range, the effective period lasted for 12 h ranging from 9 h before to 3 h after the tumour cell injection. Similar suppressive effect was also observed in the spontaneous lung metastasis. These data suggest that careful assessment of effective dose and duration of low dose TBI on human metastasis could provide a new therapy to suppress clinical metastasis. PMID- 8465020 TI - Total body irradiation in Hodgkin's disease. PMID- 8465021 TI - Combined modality therapy in high dose radioneurosurgery. PMID- 8465022 TI - A trial of Ro 03-8799 (pimonidazole) in carcinoma of the uterine cervix: an interim report from the Medical Research Council Working Party on advanced carcinoma of the cervix. AB - A randomised controlled clinical trial of Ro 03-8799 (pimonidazole) was performed in advanced stage II and stage III squamous cell carcinoma of the uterine cervix. A total of 183 patients were contributed by 15 centres in Western Europe and coordinated by the Medical Research Council Trials Office in Cambridge. Analysis has shown poorer local tumour control with a hazard ratio (HR) of 2.1 [95% confidence interval (CI) 1.2 to 3.7] and survival with a HR of 1.6 (95% CI 1.0 to 2.5) in the group given the Ro 03-8799. These results were not materially affected after adjustment of stage or haemoglobin levels in stratified analysis or to inadequate radiotherapy being given to the sensitiser group. A true adverse effect caused by the drug is a possible cause and this might be related to a drug induced impairment of blood supply to the tumour. When compared with results recorded previously for advanced cervical carcinoma treated by radiotherapy, it was apparent that the tumour control and survival in the sensitiser arm was similar, but the control arm showed results superior to those previously recorded. Whatever is the explantation it can certainly be concluded that the radiosensitising drug, pimonidazole, gave no benefit in the radiotherapy of advanced cervical cancer. PMID- 8465023 TI - [Day-night differences of arterial pressure in "white coat" arterial hypertension]. AB - Prevalence and day-night differences of blood pressure (BP) are studied in "White Coat" Hypertension (AHT). An outpatient register of BP was performed during 24 hours in 95 patients with mild AHT. "White Coat" Hypertension was defined when diastolic BP during the day was below 90 mmHg (WCH group) and with no "White Coat" Hypertension (non-WCH) when it was over said figure. BP values for WCH group (n = 36) in comparison with non-WCH (n = 59) were: Day period 130 +/- 13/85 +/- 4 versus 143 +/- 14/99 +/- 7 mmHg (p < 0.001; p < 0.001). Night period 119 +/ 18/74 +/- 8 versus 127 +/- 15/84 +/- 8 mmHg (p < 0.05/p < 0.001). Day-night differences in BP were lower in WCH in comparison with non-WCH group: 11 +/- 9/11 +/- 8 versus 17 +/- 10/15 +/- 7 mmHg (p < 0.01; p < 0.01). A positive correlation was observed between BP variability in 24 hours and day-night difference in non WCH group (Systolic BP: r = 0.512, p < 0.001; Diastolic BP: r = 0.676, p < 0.001). This correlation was not found in the WCH group. "White Coat" Hypertension is present in 38% of the subjects with mild AHT and could constitute an independent aspect of the alert reaction. PMID- 8465024 TI - [Clinical diagnosis of Biswanger's disease]. AB - Fifty patients with periventricular hypodense lesions in cerebral CAT (leucoaraiosis) were included in a prospective study. All of them were intensively evaluated considering both the clinical and neuropsychological aspects. Fifteen of these patients were diagnosed of dementia following the criteria proposed by Bennett et al for Binswanger's disease. The group of patients with dementia was compared with the rest of patients with leucoaraiosis from the radiological, semiological and neuropsychological aspects; the incidence of vascular risk factors and the score obtained in the Ischemic Scale were also compared. We found that the patients with dementia have, in the CAT study, more severe periventricular lesions than the rest of patients. We have not found any significative differences in the incidence of vascular risk factors. Deambulation disorders, constructive apraxia and visual-perceptive disorders were the symptoms more strongly related with dementia, even tough only the latter two showed this relationship in the statistical multivariant analysis. Differences in the score of test and scales were highly significant. We think that Bennett's criteria are of great value for the clinical diagnosis of Binswanger's disease. PMID- 8465025 TI - [Comparative study of pneumococcal bacteremia in patients with and without HIV infection]. AB - A retrospective study of bacteriemias due to S. pneumoniae in adults is performed, from all the cases observed in our hospital during the 1989-1990 period. We compare the clinical characteristics of the disease depending if the affected patients were infected or not by the human immunodeficiency virus (HIV). In the considered period bacteriemia due to S. pneumoniae has been diagnosed in 12 patients with HIV infection and 29 without it. Ten of the twelve patients with HIV infection (83.3%) were in Stage IV (CDC) of the disease, staying the rest in a less developed phase of the disease. Age was significantly higher in non-HIV patients (p < 0.001) and a high percentage of patients in this group (75%) showed some disease considered as predisposing to bacteriemia due to S. pneumoniae. When a respiratory foci was present, VIH positive individuals showed more frequently bilateral radiologic infiltrates and less frequently pleural effusion. Leucocyte count when diagnosis was done were significantly higher in non-HIV group. Sensibility of isolated S. pneumoniae was similar in the two groups, being the immediate mortality related with bacteriemia due to S. pneumoniae higher in the non-HIV group. In our center 29.3% of bacteriemias due to S. pneumoniae are diagnosed in patients with HIV infection. This disease in itself could constitute an added risk factor in the development of bacteriemia due to S. pneumoniae. PMID- 8465026 TI - [Cardial adenocarcinoma following sclerotherapy of esophageal varices: presentation of a case and review of the literature]. AB - The case of a patient with a diagnosis of chronic alcoholic hepatopathy is discussed. This patient developed an adenocarcinoma of the esophageal-gastric union after several sessions of sclerotherapy indicated to treat hemorrhage of esophageal varices. Similar cases published until now are reviewed. PMID- 8465027 TI - [Psittacosis of avian origin as etiology of community-acquired pneumonia with severe onset]. AB - We present two cases of community acquired pneumonia (extra-hospital) of severe onset, secondary to Chlamydia psittaci of avian origin. Each patient have bought a parakeet in the same pet-shop, and took care of them personally. Both developed a respiratory insufficiency, one of them needing mechanical ventilation. Out of nine relatives to whom serological determinations were performed, there was evidence of infection in two of them, but only one referred an auto-limited febrile syndrome during that period of time. Psittacosis incidence is discussed as origin of community acquired pneumonias, as well as its epidemiology, diagnosis and treatment. PMID- 8465028 TI - [White coat hypertension: a debatable issue]. PMID- 8465030 TI - [Mediastinal cystic mass]. PMID- 8465029 TI - [Angiotensin-converting enzyme inhibitors: effects on renal physiology and applications in hypertension and renal disease]. PMID- 8465031 TI - [Diet and cardiovascular disease]. PMID- 8465032 TI - [Malignant neuroleptic syndrome treated with bromocriptine]. PMID- 8465033 TI - [Anaphylactic shock caused by spontaneous rupture of hepatic hydatid cyst into inferior vena cava]. PMID- 8465034 TI - [Late seroconversion in Legionella pneumophila pneumonia]. PMID- 8465035 TI - [Pulmonary cavitations caused by Pneumocystis carinii in an HIV+ patient]. PMID- 8465036 TI - [Guillain-Barre syndrome as initial manifestation of human immunodeficiency virus infection]. PMID- 8465037 TI - [Organic or functional? Diagnoses not necessarily exclusive. Report of a patient with vomits]. PMID- 8465038 TI - [Mediastinal benign teratoma. Report of a case]. PMID- 8465039 TI - [Idiopathic polyneuritis and IgA monoclonal gammapathy]. PMID- 8465040 TI - [Dehydroepiandrosterone sulfate and testosterone in acute myocardial infarction]. PMID- 8465041 TI - [Ventricular tachycardia in myotonic dystrophy]. PMID- 8465042 TI - [Effectiveness of endoscopic sclerotherapy in the treatment of bleeding esophageal varices]. AB - 92 patients to whom urgent endoscopy and sclerotherapy of esophageal varices was performed are studied retrospectively. After the bleeding episode, elective sclerosis sessions were performed to eradicate varices, to prevent hemorrhagic complications and post-sclerotic stenosis somatostatin, H2 antagonists and sucralfate were administered. The Total number of sessions was 331, with a mean of 3.6 per patient (range 1-10). Immediate hemostasis was achieved in 93% of patients, with an early relapse in 10.4% of them. Hemorrhagic relapse two years following therapy was 35.8%. Mortality was 41%; 8% of the decreased patients belonged to Child's A functional grade, 24% belonged to B; and 68% to C. There was a 44% of complications, but only one death was due to the technique. No patient developed symptomatic stenosis neither hemorrhage secondary to esophageal ulceration. We conclude that endoscopic sclerotherapy is one of the principal therapeutic options in the hemorrhage due to esophageal varices, although new studies are necessary to define the role of somatostatin and H2 antagonists in the prophylaxis of complications. PMID- 8465043 TI - [The study of zinc in osteonecrosis]. AB - Plasmatic, urinary and intra-erythrocytic zinc levels did not modify in patients with head of femur aseptic osteonecrosis (HFAO), except for those patients with raised alkaline phosphatase who showed a diminution in zinc plasmatic levels, being found a negative correlation between plasmatic zinc levels and a raise in serum alkaline phosphatase. A raise on the latter would mean a raise on the osteoblastic activity in a repair intent from the bone of the small trabecular fractures and/or of the necrotic zone which is produced in HFAO. These results show the relationship of zinc with the increase on bone metabolic activity in patients with HFAO, but the scarce previous references force to study them in depth. PMID- 8465044 TI - [The cut-off points used in chemiluminescent probes for the identification of mycobacteria]. AB - 441 strain of mycobacteria were exposed to probes marked with luminous material belonged to M. tuberculosis complex and M. avium complex. We analyzed the following points: 1. If the cut-off points obtained with our strains were in accordance to those recommended by the manufacturer, using two different luminometers. 2. If the correlation constant makes possible the conversion of the units form one luminometer to the units obtained with the other one. 3. Data for sensibility, specificity and predictive positive and negative values using different cut-off points. Cut-off points were different in all cases except for the data obtained with one luminometer using a probe belonged to M. tuberculosis complex. In this case the correlation constant could not be used. In contrast, whichever the luminometer employed was, we found no significant differences between sensibility, specificity and predictive values. PMID- 8465045 TI - [Infections in the postoperative period of a liver transplant. A comparison of 2 protocols for anti-infectious prophylaxis]. AB - We discuss the incidence of infection in 198 liver transplants during the immediate post-surgical period. All of them were treated with protocols with anti infective prophylaxis, and have been divided in two groups regarding the antibiotic scheme used, in the second of said groups we have included parenteral vancomycin. Global incidence of infection was different for both groups (46.9% in group A and 15.3% in group B) (p < 0.01). We stress that the most frequent germ found in the cultures of the group without vancomycin was Staphylococcus aureus, with a great difference between groups (p < 0.01); global incidence of pneumonias was also different between both groups (p < 0.05). After the introduction of vancomycin in the second group the most frequent found germ was Candida but with a low percentage. Gram-negative germs appear preferably in both groups when hospital stay was over 10 days. It is important to stress that transplanted patients who did not show rejection got significantly lesser infected (p < 0.05) than patients who shown rejection. We think that parenteral prophylaxis with ceftazidime and vancomycin, associated with oral-rhino-gastric decontamination, is useful for the control of early infections in patients with liver transplant. PMID- 8465046 TI - [Salmonellosis and ulcerative colitis. A case report and review of the literature]. AB - A propos of a case of intestinal infection due to Salmonella non typhi in a patient with ulcerative colitis, we have reviewed the disease and, therefore ran a search through the scientific literature in which we have found 16 cases of ulcerative colitis diagnosed in a clinical setting which began as an enterocolitis due to Salmonella. Bacteriological studies, clinical evolution and response to treatment, normally allow to differentiate between the two clinical entities. Colitis due to Salmonella and ulcerative colitis can coexist in the same patient. Duration of the clinical manifestations oven four weeks, previous history of diarrhea with blood, the sudden worsening of a mild prolonged diarrhea, non-response to specific antibiotic treatment and fast response to therapy with corticoids of a diarrhea positive isolation of Salmonella in stools, should make us immediately think in the coexistence of a subjacent ulcerative colitis. Treatment with steroids always must be associated with systemic antibiotics if Salmonella has been isolated just before or during their administration. PMID- 8465047 TI - [Psoas abscess. The diagnostic and therapeutic considerations in 5 patients]. AB - Five cases of psoas abscesses are discussed, four pyogenes and one tuberculous, the current etiology of this process, together with its pathogenesis and clinical manifestations are discussed. In all of them the guided punction through Computerized Axial Tomography (CAT) has been the way to diagnose and treat the process. Utility of this technique considering both aspects is discussed because it allows to determine the etiology and avoids the surgical drainage; even tough this therapy should be individualized in each case, probably is in primary staphylococci abscesses where this therapeutic option is best indicated. PMID- 8465048 TI - [A toxic syndrome and subcutaneous nodules as the only clinical manifestation of systemic sarcoidosis]. AB - Sarcoidosis is a systemic disease with frequent cutaneous manifestations. Among these exists a predominance of the so-called unspecific lesions because of their histopathological features. Within the specific lesions, that is those which showed non-caseous granulomas, subcutaneous nodules are underlined, which have been associated with chronic sarcoidosis with a frequency of 1.4%-6%. These lesions appear during the evolution of the disease but rarely constitute an initial manifestation of it. The patient whose case is discussed had a debut with toxic syndrome and subcutaneous nodules. Histopathological study of these nodules showed the existence of non caseous granulomas formed by histiocytes, epithelioid cells, Langhans and foreign body giant cells. Lobulet hepatic granulomas were showed together with mediastinal pulmonary captation of gallium. We conclude that sarcoidosis must be considered when performing the differential diagnosis of the disease which debut with subcutaneous nodules. PMID- 8465049 TI - [An analysis of drug advertising in non-specialty medical journals]. AB - It has been evaluated drug advertisement in four medical journals during 1989. A questionnaire allows us to evaluate pharmacological and advertising data. The main results obtained are the following: amoxicillin + clavulanic acid was the more advertising drug; the ratio publicity/pharmacological information was 3:1; 60% of the advertising products were new drugs, and only a 6% were essentials drugs according to WHO; slogans were acceptable; generally, aspects such as dosage and toxicology are referred. However, it is necessary to improve information about drug use in elderly patients, patients with impaired renal functional, as well as the necessary information in adverse drug reactions. PMID- 8465050 TI - [Retroperitoneal hematoma: a computed tomographic study]. PMID- 8465051 TI - [The Sandostatin treatment of digestive carcinoid tumors]. PMID- 8465052 TI - [Spontaneous bacterial peritonitis in systemic lupus erythematosus]. PMID- 8465053 TI - [Toxic hepatitis due to fosfosal]. PMID- 8465054 TI - [Dermatomyositis in a patient with 2 neoplasms]. PMID- 8465055 TI - [Hysteria: the diagnostic error problem]. PMID- 8465056 TI - [Tuberculous pericarditis as the first manifestation of AIDS. The indication for diagnostic pericardiocentesis]. PMID- 8465057 TI - [Sneddon's syndrome: apropos a case]. PMID- 8465058 TI - [A pulmonary abscess due to Rhodococcus equi in an AIDS patient]. PMID- 8465059 TI - [Superior mesenteric vein thrombosis and the primary antiphospholipid syndrome]. PMID- 8465060 TI - [Familial hypercalciuric hypercalcemia. A family study]. PMID- 8465061 TI - [Working conditions of nurses at public hospitals 1980 to 1990]. AB - The 1988 and 1991 strikes among nurses were motivated by claims concerning the status of the nursing profession, wages and working conditions. A study of working conditions was carried out from two samples: 1) a cohort of nurses (N = 571) recruited in 7 hospitals and followed up in 1980 (follow up rate: 85%) and in 1990 (follow up rate: 69%); 2) a sample of nurses who began to work in the same settings between 1985 and 1989 (N = 108). The results indicate no improvement in the organisation of shiftwork on the 10 years period. Working conditions deteriorated during the last 5 years. These findings are discussed in the light of the global evolution of hospital and of the specific problems of the nursing profession. PMID- 8465062 TI - [Cost-benefit analysis of prenatal screening for trisomy 21 through analysis of HCG in maternal blood]. AB - Introduction of maternal serum markers for prenatal screening of Down's syndrome implies a redefinition of the criteria used for identifying at risk women for screening by amniocentesis, which are currently based on maternal age. On the basis of the first French prospective study of human chorionic gonadotropin measurement in maternal serum as a predictor of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement was more cost effective than one relying on maternal age alone. A cost-benefit analysis (using the "avoided" lifelong costs of care for a trisomic 21 child that are allowed by prenatal screening) would justify lower hCG cut-off values and an higher detection rate of Down's syndrome (74.5%) than other decision rules based on alternative principles such as: equalization to 1% of fetal risk of Down's syndrome for access to amniocentesis at all maternal ages or equalization to 1/1000 of fetal risk of Down's syndrome among women not undergoing amniocentesis. However, results of the cost-benefit analysis are very sensitive to other factors such as the cost associated with loss of a normal fetus due to iatrogenic risk of amniocentesis (false positives of hCG). Ethical and value-laden issues that necessarily underlie economic evaluation of screening programmes, as well as other decision rules based on equalization of acceptable risk for each maternal age, are discussed. PMID- 8465063 TI - [Urban atmospheric pollution and mortality: analysis of epidemiological studies published between 1980 and 1991]. AB - This paper analyses 14 epidemiologic investigations (published from January 1980 to September 1991) about the relationship between urban air pollution and mortality. Air pollution indicators and mortality indicators are examined. Methods to analyse the relationships between these two kinds of indicators are classified according as they bring "qualitative information" trying to answer the question: "is there any relationship between air pollution and mortality?" or according as they try to quantify this relationship. Results are presented by author. Confounding factors and means to take them into account are described. This paper ends by a discussion about interest and limits of these studies. It emphasizes the importance of the collaboration between metrologists of urban air pollution and epidemiologists. PMID- 8465064 TI - [Prevalence of severe mental retardation and trisomy 21 in 3 generations: 1972, 1976, and 1981]. AB - With the aim of studying whether improved prenatal and perinatal care would lead to a decrease in the prevalence of severe mental retardation and/or in Down syndrome, handicapped children born in 1972, 1976 and 1981 and residing in 14 French "departements" were systematically registered in 1985-86 and 1989 in collaboration with the "Commissions Departementales de l'Education Speciale" (CDES), which centralizes requests for specialty services. The findings showed a stable rates of Down's Syndrome (0.7 p. 1000 in 1972, 0.8 p. 1000 in 1976 and 0.9 p. 1000 in 1981) and of severe mental retardation (1.6 p. 1000 in 1972, 1.5 p. 1000 in 1976 and 1.6 p. 1000 in 1981) in the three generations among children below the age of 9 years. The survey shows that implementation of perinatal health care programs starting in the 1970s, had not been followed by a decrease of severe mental retardation prevalence or Down syndrome prevalence across the three generations 1972, 1976 and 1981. PMID- 8465065 TI - Determinants of estrogen replacement therapy use in northern Italy. AB - Socio-demographic characteristics, general lifestyle habits and menstrual and reproductive history were compared in 83 women aged 45 years or more who had at some time used estrogen replacement therapy (ERT) and 1759 never users interviewed as control subjects in the framework of a large case-control survey on risk factors for gynecological neoplasms conducted in Northern Italy. ERT use was strongly related to social class and level of education. The odds ratio of "ever" use was 3.0 (95% confidence interval, CI, 1.8-5.1) for women with 12 or more years of education, compared with those with less than 7 years. No relationship emerged between marital status and ERT use, but parous women tended to be less frequently ever users than nulliparous, and ERT use decreased with increasing number of births (chi 2 1 trend = 10.51, p. = 0.001). Post-menopausal women reported more frequent ERT use than peri-menopausal ones, and among post menopausal subjects the use was more frequent in those reporting earlier age at menopausal (chi 2 1 trend = 5.33, p = 0.02). There was no association between smoking habits and ERT use, but Quetelet's index was inversely related to the use of ERT. PMID- 8465066 TI - Number of sexual partners and age at first intercourse in subsequent generations of Italian males and females. AB - Trends in the number of sexual partners and in age at first intercourse were analyzed using data on 706 men and 1206 women drawn from the hospital control groups of two case-control studies conducted since 1981 in Northern Italy. The overall lifelong mean number of sexual partners was 7.5 +/- 12.8 for men and 1.4 +/- 1.8 for females. The mean number of sexual partners was 6.0 for men born between 1910 and 1919, and 7.3, 9.0, 6.3 and 5.5 for subsequent 10 year birth cohorts. Mean age at first intercourse was 20.7 for the cohort born in 1910-19 and was fairly stable in men born after 1919, ranging from 18.4 to 18.8. Women had a substantially lower number of sexual partners than men in each subsequent birth cohort. However, the mean number of sexual partners increased from 1.1 in the 1910-19 cohort to 1.2, 1.2, 1.4 and 2.3 in subsequent birth cohorts, and the mean age at first intercourse decreased from 23.6 years to 23.1, 22.7, 21.3 and 19.7. These figures should be considered with caution, on account of the non representativeness of the sample and of a possible under-reporting of number of partners by women. Still, Italian women, although not necessarily men, report substantially fewer sexual partners than northern European on American ones. PMID- 8465067 TI - [Evaluation of quality of life: construction of a scale]. AB - Research in public health has recently tended to take a more global perspective when considering the individual patient. In addition to a measure of functional status, the integration of the disease into the daily life of the individual, or his quality of life is what is being evaluated. This concept, while relatively recent (10-15 yrs), is the result, in part, of changes in the diagnosis and treatment of patients, particularly those with chronic and severe diseases. In clinical trials, what is sought is a measurement of change in the level of well being during the evolution of an illness or of the different levels that exist between two groups. The validation of a scale of this type requires both a qualitative and a quantitative phase with attention being paid to the methodological issues in scale development Specific statistical techniques are used to modify evolving versions. The adaptation of an existing scale into another language requires a rigorous qualitative phase before the quantitative phase is begun. PMID- 8465068 TI - [Inter-rater agreement of a functional analytical measure of the upper limb]. AB - The determination and the follow-up of a patient having an upper limb lesion need a functional assessment instrument. This study examined the inter-rater agreements of the "400 points Measure", between two occupational therapists and a physiotherapist. One occupational therapist only had already used this instrument. The others raters received preliminary training with an audio-visual projection. The scale included four tests with 57 activities: (E1) Functions of the hand and fingers, (E2) Prehension strengths, (E3) Handling and displacement of things, and (E4) Functions with both hands. The study population consisted of 85 patients of a rehabilitation centre. Inter-rater agreements were quite good for E1 and E3, but they were not as good for E4, that included several functions of both limbs. For E1, the physiotherapist rated slightly but significantly different from the other raters. For E3 and E4, the occupational therapist having used the scale, rated lower than the other raters; but the difference was small. For E1, the physiotherapist rated higher than the two occupational therapists for the elderly. A discussion with the raters and a new trying showed that the differences will be small when the above training is completed by a short training about the standard gestures and the detection of the abnormalities. PMID- 8465069 TI - Case-control study of fibrocystic breast disease. AB - An epidemiological case-control study of FBD has been conducted to evaluate the differences observed between cases and controls in relation to the presence or absence of clinical findings and risk factors for fibrocystic breast disease (FBD). A total of 334 patients with FBD were identified among 6,232 women aged 40 59 who had participated in the National Breast Screening Study in Montreal while 340 age-matched controls were selected at random from the same cohort. All women were interviewed by a well trained nurse. Controls were significantly heavier and had a higher body mass index (BMI) than cases; however, cases had longer school attendance than controls. The menstrual cycle was shorter in cases and the number of pregnancies was greater in controls. Significant odds ratios were observed for BMI (O.R. = 0.72, 95% CI = 0.51 - 1.02) suggesting that a higher value of BMI had a rather protective effect; a similar pattern was observed in women using oral contraceptives. Since nodularity was strongly associated with FBD, it was excluded from a model of logistic regression; in this instance, longer school attendance (> 12 years), older age at menopause (> 45 years) and breast pain were significantly associated with an increased risk of FBD. PMID- 8465070 TI - [Mortality of cerebral infarction with auricular fibrillation. Results of a population study]. AB - To evaluate the relationship between atrial fibrillation (AF) and mortality of the cerebral infarction, we have studied in a population survey, 540 cerebral infarctions, whose 162 were with AF (30%) and 378 without AF (70%). The group with AF differs significantly from that without AF, by the higher frequency of women (62% versus 35%), older subjects (75.4 +/- 10.2 years old versus 69.1 +/- 9.7 years old), a severe loss of consciousness, a more frequent subcortical infarction on CT-Scan. During a period of 24 months, 139 patients died, 64 among the 162 patients with AF (40%), 75 among the 378 patients without AF (20%). Rates of death are different in the 2 groups with, in the group with AF, at 1, 6, 18 and 24 months a rate of 20, 24, 37 and 40 percent. To the opposite, in the group without AF, the rates are 8, 12, 16 and 20 percent. The authors try to research the factors that may explain the mortality linked to AF, and they insist on the necessity to look for AF on admission for a stroke, to identify a subgroup of stroke patients with a high risk of death. PMID- 8465071 TI - [HIV seroprevalence in pregnant women: knowledge of women of the tests used]. PMID- 8465072 TI - [Anesthetic immunopharmacology?]. PMID- 8465073 TI - [Utilization of veno-venous bypass in orthotopic liver transplantation]. AB - BACKGROUND: AIMS: The aim of the present study was to evaluate the hemodynamic effects of venovenous bypass (VVB) and its possible protective action during the clamping of the hepatic vessels carried out in the anhepatic phase of the orthotopic liver transplantation. PATIENTS AND METHODS: Forty-one liver transplant patients, 15 of whom were operated with VVB, were studied. VVB consisted of a bridge from the primitive iliac veins and the portal vein to the left axillary vein. The hemodynamic, metabolic and biologic variables as well as the components of reposition and the drugs administered were measured. The results obtained in both groups were statistically compared and analyzed. RESULTS: During the anhepatic phase the values of cardiac output did not modify in the patients operated with VVB, while these values significantly decreased in other patients. Peripheral resistances increased less in the VVB group. During the reperfusion phase there were no significant differences between the hemodynamic parameters of either group. The decrease in temperature during the anhepatic phase was significantly greater in the VVB group. CONCLUSIONS: Venovenous bypass offers greater hemodynamic stability during the anhepatic phase of orthotopic liver transplantation. PMID- 8465074 TI - [Intrapulmonary short-circuit during coronary or aortic valve heart surgery]. AB - BACKGROUND: The alterations in gas exchange during cardiac surgery was studied by the measurement of the perioperative intrapulmonary shunt. PATIENTS AND METHODS: Forty patients divided into two groups were studied. Group 1 consisted of 20 patients undergoing myocardial vascularization and group 2 consisted of 20 patients undergoing aortic valve replacement. The anesthetic technique was similar in both groups but the patients in group 1 received a continuous perfusion of nitroglycerin from the beginning of surgery plus a bolus of intranasal nifedipine 30 minutes prior to the exit of extracorporeal circulation. The measurement of the shunt was performed 5 times: following the induction of anesthesia, prior to and after extracorporeal circulation, upon termination of surgery and one hour following admission to the ICU. RESULTS: In both groups an increase of the shunt was produced at the end of extracorporeal circulation which later returned to basal levels. The increase was greater in patients of group 1 during the different phases of surgery although significant differences only existed at the beginning and end of extracorporeal circulation. The variations of the shunt were not related with the state of preoperative pulmonary function or with the duration of extracorporeal circulation. CONCLUSIONS: Although intrapulmonary shunt increases during cardiac surgery, especially coronary, its clinical transcendence is nul and no special measures are required. PMID- 8465075 TI - [The contribution of "La Espana Medica" (1856-1866) to the introduction of anesthesiology in Spain]. AB - The aim of this study was to analyse the contribution of "La Espana Medica " (1856-1866) to the introduction of anesthesiology in Spain. Thirty-seven articles on anesthesiology were published, with 19 articles (51.35%) being originals from spanish authors and 18 (48.64%) from abroad. By means of this medical newspaper from Madrid, Spanish physicians received information concerning the latest changes in anesthesiology with special emphasis on the introduction of amylene. PMID- 8465076 TI - [Anesthesia in a case of hyperkalemic familial periodic paralysis]. AB - Periodic familial hyperpotassemic paralysis is a dominant autosomic disease of brief periods of acute flaccid paralysis with complete posterior recovery. During surgical-anesthesia a number of factors concur which may trigger a paralytic episode. To this effect anesthetic drugs such as barbiturates and muscle relaxants have been involved. The case of a 12 year old patient with familial hyperpotassemic paralysis who received general anesthesia with propofol and atracurium besylate for emergency appendectomy is presented. During surgery the plasma levels of potassium were monitored and prophylaxis of the factors which potentially trigger a paralytic picture was performed. Both, the perioperative and the postoperative period, were without complications. PMID- 8465078 TI - [Presentation of 2 cases of neuromuscular excitation associated with propofol]. AB - The cases of two patients who received peridural and intradural anesthesia and propofol as sedation are presented. In one case generalized tonic and clonic convulsions, and in the other, opisthotonos appeared. Neither patient had previous neurologic disease nor, in the context of complications, did other causes to explain the same appear except for the possible association with propofol to which similar secondary effects have been described. PMID- 8465077 TI - [Anesthesia in a case of hereditary angioneurotic edema]. AB - The case of a 51 year old woman diagnosed with hereditary angioneurotic edema (HANE) requiring hospital admission on one occasion is presented. The patient was scheduled for abdominal hysterectomy of uterine myomas. Upon presentation to the authors, the patient was not under treatment and was asymptomatic. The patient was given 1000 units of C1-INH two hours prior to surgery. The operation was performed under peridural anesthesia to which no complications were presented. Specific treatment included: short term prophylaxis prior to surgery with C1-INH or fresh plasma and/or antifibrinolytic and hormonal agents. The authors considered that the locoregional techniques are elective to avoid tracheal intubation. PMID- 8465079 TI - [Dysfunction of the central nervous system in the postoperative period]. PMID- 8465081 TI - [Accidental subdural block during epidural anesthesia]. PMID- 8465080 TI - [Peri-thyroidectomy pulmonary edema: various etiopathogenic considerations]. PMID- 8465082 TI - [Boerhaave syndrome: implications for the anesthesiologist]. PMID- 8465083 TI - [Hereditary angioneurotic edema: anesthetic considerations]. PMID- 8465084 TI - [Milrinone, heart surgery, and hyperthyroidism]. PMID- 8465085 TI - [0.0625% bupivacaine compared with 0.125% bupivacaine continuously perfused epidurally during vaginal delivery]. AB - BACKGROUND: The effects of two continuous epidural perfusions of bupivacaine at different small concentrations on maternal analgesia, motor paralysis, the progress of delivery and the newborn were compared. PATIENTS AND METHODS: Forty primigravida patients were divided into two homogeneous groups, A and B, with 20 patients in each. Group A patients were administered a perfusion of bupivacaine at 0.625% and those of group B received a perfusion of bupivacaine at 0.125%. Both perfusions were administered at 10 mg/hour. The following variables were collected: analgesia (visual analogic scale), time of perfusion, local anesthetic doses, re-injections, tenesmus, APGAR at the first minute, APGAR at 5 minutes, use of forceps and motor paralysis. RESULTS: The perfusion of bupivacaine 0.125% (group B) was more effective in the control of pain since no re-injections were required in this group. The time of perfusion and delivery was significantly less (p < 0.05) in group B (2.95 +/- 0.74 hours) than in group A (3.42 +/- 0.62 hours). There were no significant differences in the total dose (group A: 55.9 +/ 14.09 mg and group B 57.47 +/- 9.06 mg), tenesmus and APGAR: Instrumentation during delivery carried out in both groups (55% in group A and 30% in group B) was at the limits of significance (p = 0.057). Motor paralysis of the lower limbs did not surpass the value of 1 of the modified Bromage scale in either group. CONCLUSIONS: Both techniques (continuous perfusion of bupivacaine at 0.0625% versus bupivacaine at 0.125%) are effective in the control of pain during the second stage of labour with the perfusion of the latter dose (12.5 mg/hour) being more advantageous by diminishing the length of delivery and achieving continuous analgesia. PMID- 8465086 TI - [Is it possible to obtain a reduction of body weight exclusively via a loss in fat mass? Experience with d-fenfluramine]. AB - Aim of the study was to observe if the administration of an anorectic drug, d fenfluramine, in addition to hypocaloric diet, could influence the body composition and adipose mass distribution during a weight decrease programme in 17 obese women. Drug's effects plus diet on body weight changes were compared with those of a "only-diet programme" in another group of 18 obese subjects, sex and age matched. Both groups were observed for a 6-month period. All subjects were selected on the base of Index Body Weight % within 120-200 and without any therapy for other diseases. Blood samples were drawn before, during (3rd month) and after the period of observation for the measurement of OGTT, serum lipids, liver and kidney function parameters, blood cells count. Body weight and height, body composition, waist-to-hip ratio were also evaluated. Results documented: 1) significant reduction of body weight in the group kept on the combined therapy; 2) significant variation of body composition with increment of fat free mass and adipose mass decrease; 3) significant improvement of glucose tolerance, liver and kidney function parameters. In conclusion, our data show beneficial effects of d fenfluramine on appetite reduction, influencing the carbohydrates assumption and the consequent fat mass loss with a good tolerability of the drug. PMID- 8465087 TI - [Interferon therapy in liver cirrhosis]. AB - Ten patients were given 3MU/3 times/week of r-interferon alpha 2b for 4 months; six patients were given 1MU/3 times/week for 4 months. The choice of these regimes has been based on the number of platelets. Among the patients treated with 9MU/week we observed a type I response (alanine-aminotransferases normalization) in 40% of cases, a type II (ALT fifty percent reduction) in 40% of cases, and a type III (no response) in 20% of cases. Among the patients treated with 3MU/week we observed a type II response in 16.7% and a type III in 83.3% of cases. Treatment of Child A liver cirrhosis with r-interferon demonstrates to rise, therefore, the same percentage of response which are obtained in the treatment of chronic active hepatitis, when the same doses are administered (9MU/week). PMID- 8465088 TI - [Nuclear magnetic resonance in the neurological complications in a case of thrombotic thrombocytopenic purpura]. PMID- 8465089 TI - [Native anti-DNA antibodies and the synovial fluid. A report of a problematic clinical case]. AB - The authors report the unusual case of a 30-years-old woman affected by bilateral gonarthritis with anti-ds DNA antibodies at higher level in synovial fluid than in serum. This finding, and the presence of an intensive infiltration of polyclonal plasma cells in the synovial membrane, studied by biopsy, lead to suppose a local production of autoantibodies with a probable pathogenetic role. PMID- 8465090 TI - [The clinical picture of anxiety. The problems and prospects]. AB - Recent studies on anxiety as well as clinical practice submit several questions regarding definition and nosography. The role played by the serotonergic system with reference to different symptoms is also discussed. The solution of these questions has important therapeutical implications. PMID- 8465091 TI - [The microcirculatory pathogenetic hypothesis of neoplasm proliferation]. PMID- 8465092 TI - [The current situation of malaria]. PMID- 8465093 TI - [Integrated teaching in the new regulations of studies in medicine and surgery]. PMID- 8465094 TI - Tumor necrosis factor/cachectin in Crohn's disease. Relation of serum concentration to disease activity. AB - Inflammatory mediators seem to be involved in the pathogenesis of Crohn's disease. Tumor necrosis factor is a primary mediator of inflammatory responses which causes metabolic effects related to tissue wasting. The aims of this study were to establish the presence of tumor necrosis factor in Crohn's disease patients, to determine of its serum levels reflect disease activity and to examine the relationship if this cytokine with other assessments of the activity of the disease. Serum concentration of tumor necrosis factor, measured with a biological assay, was significantly raised in 56 Crohn's disease patients (201 determinations) as compared with 44 controls (P < 0.0001). Patients with inactive disease had significantly lower tumor necrosis factor levels (3.58 +/- 0.55 ng/mL) as compared to patients with active disease (8.17 +/- 1.01 ng/mL). There was a significant correlation between serum tumor necrosis factor concentration and disease activity (r = 0.237, P < 0.002). Higher tumor necrosis factor levels were detected in patients with colonic involvement (ileocolitis and colitis) as compared with ileal localizations, and the difference was significant (t = 2.16, P < 0.05). Besides, it correlated negatively with albumin, haemoglobin and cholesterol. PMID- 8465096 TI - [A new way of training physicians at Italian universities. The university tutor: a new aspect]. PMID- 8465095 TI - [Tuberculosis, still an unsolved problem]. PMID- 8465097 TI - [Differentiating agents in myelodysplastic syndromes. Analysis of personal cases]. AB - The Myelo-Dysplastic Syndromes are a heterogeneous group of diseases which includes patients with different prognosis. There is no agreement about the management and the therapeutic strategy must be based on many individual parameters, particularly the age of the patients and their performance status. The therapeutic options range from no cytotoxic therapy for low-risk patients up to more aggressive treatment for high-risk patients, with disappointing results except for the very few cases eligible for allogenic bone marrow transplantation. The leukaemic cell can be induced to differentiate, so losing its self maintenance potential; different drugs such as Interferon, vitamin D3, retinoids and arabinosyl-cytosine (low doses) have shown a differentiating action on myeloid blasts in "vitro". We summarize the general strategy in the treatment of myelo-dysplastic syndromes based on literature data, and on our results about the efficacy and tolerance of a combination of the above mentioned differentiating drugs, in a group of 27 elderly patients affected by myelodysplastic syndrome with poor prognosis. We obtained 14 objective responses (52%), and the median overall survival of these patients have been compared with that of 25 patients with severe myelodysplastic syndrome treated with a conventional regimen. In the 27 patients receiving the differentiating combination the median survival was found to be 14.7 months, versus 8.4 months for the control group. The results obtained are encouraging about the tolerance and the efficacy of this combination in elderly patients with a poor MDS prognosis. Further randomized studies are necessary to establish whether this treatment can really improve the survival in this group of patients. PMID- 8465099 TI - [Localization of rheumatoid arthritis at the craniocervical junction]. PMID- 8465098 TI - [Monovascular coronary disease in the pre-angioplasty era]. AB - Single-vessel coronary disease has been considered so far a benign condition, for which the medical therapy may represent the optimal treatment. In order to assess the effectiveness of this approach, we studied 323 patients who had come to our attention for ischemic heart disease and resulted affected by single-vessel coronary artery disease. From our data it appears that single-vessel coronary artery disease is frequently associated with myocardial infarction and post infarction aneurysm. Coronary angiography indicated that left anterior descending coronary artery is the most frequently affected vessel, and that its involvement is often associated with lethal outcome. Forty-two out of the 323 patients underwent coronary artery bypass surgery; the remaining patients were medically treated. Surgical patients showed a better improvement respect to the medical group, while survival was not statistically different. An unexpected result was the relatively high risk in circumflex artery lesion. These data may justify a broader utilization of invasive therapy in recent onset angina, in light of the excellent results recently obtained with percutaneous transluminal coronary angioplasty. PMID- 8465100 TI - [Cocaine poisoning in acute renal insufficiency]. AB - We report the case of a young man who developed acute renal failure after ingestion of cocaine wrapped in foil. We did not find either clinical or clear biochemical signs of rhabdomyolysis. The possible role of high blood cocaine level in the development of acute renal failure has been speculated and a direct vasoconstrictive effect on renal vessels followed by acute tubular necrosis has been hypothesized. PMID- 8465101 TI - [Calcification of the basal ganglia and Fahr disease. Report of two clinical cases and review of the literature]. AB - Computed Tomography (CT) is superior to conventional skull radiographs in detecting calcifications of the basal ganglia. Basal ganglia calcification has been associated with different conditions, abnormality in the calcium-phosphorus metabolism being the most common of these associations. Some patients, without any evident disease, are well documented and called idiopathics of Fahr's syndrome; less numerous patients present familiar trait, with autosomal dominant inheritance. The correlation of neurological impairment with symmetrical calcification of basal ganglia is not so frequent. Here we present two cases of Fahr's disease, in whom CT aspects were very similar, but the neurological manifestations were different. The review of the literature shows, now, that there is no definite pathogenesis of basal ganglia calcifications. PMID- 8465102 TI - [Ultrasonographic changes in the abdominal organs in the 10th decade of life]. AB - 10 patients in perfect health, aged between 90 and 101 (mean age: 93 +/- 3), have been studied with echography in order to investigate the possible changes in volume and echo-pattern of abdominal organs, linked to the "physiological" aging. Our resulting data (reduced volume of liver and kidneys, changes in echo-pattern of pancreatic parenchyma, reduced thickness of renal cortical-medullary) seem to confirm the well known data of an atrophic change interesting the parenchyma of abdominal organs in aging: this latter, however, remains compatible with function preservation. PMID- 8465103 TI - [Microalbuminuria: theoretical bases and new applications]. AB - The constant presence of albumin, as detected by common biochemical methods, in multiple urine samples of a patient, was first considered by Bright, in 1836, as a cardinal sign of renal disease ("clinical proteinuria"). Since then this view was widely adopted for studying the clinical evolution of the patients with diabetes mellitus, whose high risk to develop proteinuria and subsequently a progressive decline of renal function was well known. Thus the finding of "clinical proteinuria" by traditional, merely biochemical techniques, has been considered for more than one century as the opening event in the onset of diabetic nephropathy, and a distinctive sign of glomerulopathy in general. More recently, this view has been deeply criticized, mainly because it lies on the implicit assumption that the sensitivity limits of the biochemical tests for the detection of urinary protein concentrations (about 300 mg/dl), coincide with the ones that can distinguish non nephropathic from nephropathic patients (either diabetic or not). Indeed new techniques, that detect urinary proteins down to 1 microgram/ml, have shown that the upper limit of protein excretion in healthy people is well below the minimum concentration detectable by all the traditional tests. Therefore a new clinical entity, named "microproteinuria" has been defined, meaning the urinary excretion rate ranging between the "physiological" and the "clinical" proteinuria; its pathophysiologic, diagnostic and prognostic significance has been extensively evaluated in the last 20 years. Microproteinuria has been shown to represent a crucial event in the natural history of the diabetic nephropathy; in diabetic patients it is strictly related to the risk of future (months to years) development of overt nephropathy and chronic renal failure, and it may predict the risk of macroangiopathic complications. More recently new settings have been proposed for the study of microproteinuria, as an early and sensitive marker of cardiovascular diseases in hypertensive non diabetic patients and even in non hypertensive non diabetic elderly people. The role of microproteinuria in the diagnosis and follow-up of many non-diabetic glomerulopathies is a very interesting though still unexplored field. PMID- 8465104 TI - [Bile acids in the therapy of chronic liver diseases]. AB - In the last 10 years, interest about the employment of bile acids, especially of ursodeoxycholic acid (UDCA), in the treatment of chronic liver diseases has increased. The mechanism has not been completely explained yet, but this agent has been thought to act mainly by making bile less toxic for the liver cells, reducing the fraction of hydrophobic detergent bile acids. UDCA is effective in decreasing serum concentrations of liver enzymes in chronic liver diseases, especially in those associated with cholestasis. This effect discloses new perspectives about the employment of this agent, even in association with other drugs, i.e. interferon; however, further investigations will be necessary in order to standardize the use of UDCA in the treatment of chronic liver diseases. PMID- 8465105 TI - [Dangerous errors due to similar names of diverse drugs]. PMID- 8465106 TI - [Challenges and perspectives in rehabilitation. Recommendations for further development in rehabilitation]. PMID- 8465107 TI - [Occupational and vocational rehabilitation of psychiatric patients: a control and attribution theory approach to examining the effect of working conditions]. AB - In recent years, work and occupational activity have come to assume a therapeutic orientation in the rehabilitation of persons with mental illness. The study presented addressed the specific ways in which work activities during rehabilitation programme participation may act in a manner conducive to rehabilitation. The findings point to a positive relationship between the opportunities objectively available in the work setting for rehabilitees to influence aversive conditions or occurrences and their work-related subjective well-being. A second step enabled us to show that subjective well-being is determined less by the situation objectively at hand but primarily by the mentally ill rehabilitees' perceptions of influenceability and, hence, the experience of controllability. Further, examination of the rehabilitees' attributional patterns concerning the various control experiences revealed that the extent to which their subjective well-being is affected is mediated cognitively. The findings are discussed in view of their implications for the vocational rehabilitation of persons with mental illness. PMID- 8465108 TI - [Vocational promotion of psychiatrically handicapped patients in a Frankfurt am Main vocational training center]. AB - In 1988, the Frankfort on Main Vocational Retraining Centre had decided in favour of increased, on-going admission of psychiatrically disabled adults, offering opportunities for their vocational education. The centre's objective is to enable psychiatrically disabled rehabilitees to successfully complete formal occupational training in as "normal" a setting as possible. This means: the Centre is a vocational rehabilitation facility, and is not directed at therapy or care. Psychiatrically disabled rehabilitees are accepted for up to 10 percent of available places in the various programme types. The overall objective is formal occupational qualification. A "training centre" open to all training orientations has been established for individualized service provision in the event of crisis situations during programme participation. Special attention is focussed on intensive, continuous further education of staff, inter alia by group supervision. PMID- 8465109 TI - [The status of medical-occupational rehabilitation exemplified by urologic tumor patients]. AB - Many patients with urological carcinomas feel able, and indeed are able, to return to work after medical treatment. From a medical, psychological and socioeconomic point of view, routine pensioning must nowadays be rejected. Vocational reintegration is prepared in an individual and comprehensive manner in facilities for medical-vocational rehabilitation (phase II). The indication for vocational rehabilitation measures depends on the prognosis, on age and motivation, as well as on treatment aftereffects. The implications of operative, radiation and chemotherapy for the timing and course of the rehabilitation measures are set out, tumour- and treatment-related restrictions in future working life are discussed from an occupational medical view. Special emphasis is placed on carcinomas that should give rise to very early initiation of vocational rehabilitation services. PMID- 8465110 TI - ["Supported employment": equal opportunity for severely handicapped men and women]. AB - This article examines the "supported employment" approach, which tries systematically to integrate severely disabled men and women into the open labour market. After describing the target population, we shall outline the specific support required, along with the benefits, risks and problems involved. Examples from a few industrialized countries, demonstrating the viability of training and employing severely disabled people, will illustrate the new approach. The activities described in this article are inn line with the goals of the ILO Vocational Rehabilitation and Employment (Disabled Persons) Recommendation, 1983 (No. 168), which calls for "research and the possible application of its results to various types of disability in order to further the participation of disabled persons in ordinary working life". PMID- 8465111 TI - [Liver transplantation in alcoholic liver cirrhosis: social psychological aspects and occupational rehabilitation]. AB - Social-psychological aspects and rehabilitation after liver transplantation were examined in 21 patients. One-year survival was not different in patients with alcoholic liver disease compared with patients with other end-stage liver disease (65% vs 71%). After liver transplantation a temporary return to alcohol drinking was observed in 3 patients (14%). 52% of patients transplanted for alcoholic liver disease are occupationally rehabilitated. Social-psychological conflicts were reported by 46%. Patients with alcoholic liver disease are potential candidates for hepatic transplantation. PMID- 8465112 TI - [Requirements for a "rehabilitation law" manual within social regulations from the viewpoint of the administrative practice]. AB - Rehabilitation in Germany falls within the purview of the various branches of the social security and public welfare system, a decentralized approach which has stood the test of time. Notwithstanding, deficits exist primarily due to a lack of up-to-date intersectoral alignment a shortcoming to be remedied by comprising rehabilitation in a separate book of the Social Code. The various social security schemes responsible for rehabilitation are attaching much importance in this context to the linkages with their specific fields of competence as well as their programming latitude being maintained. The demands to be made from an overall perspective relative to a "rehabilitation" book are set out inter alia on the example of social assistance and youth services, on terminological issues, benefit scope, needs coverage, rehabilitation principles and procedures, as well as on cooperation aspects, also clarifying differing views among the branches of our social security and welfare system. A Social Code book on "rehabilitation" should essentially be aimed at focussing the variety of rehabilitative measures in terms of a holistic rehabilitation approach, i.e., to respond to the person's overall needs by overall service provision. PMID- 8465113 TI - [Social medicine position in the rehabilitation discharge report from the viewpoint of quality assurance]. AB - The sociomedical statements given on the basis of Sociomedical Clinic apraisement of 103 patients were compared with those rendered at discharge from previous in patient rehabilitation. Discrepant judgements and evaluation problems in describing functional capacity at work are pointed out, and their causes discussed. Proposals are submitted for enhancing more effective cooperation between rehabilitation clinics and the Sociomedical Services of the pension insurance administrations. PMID- 8465114 TI - [17th International Congress and Membership Meeting of Rehabilitation International September 1992 in Nairobi, Kenya]. PMID- 8465116 TI - Mechanisms and regulation of water transport in the kidney. PMID- 8465115 TI - Urea transport in the kidney. AB - Urea transport within the kidney is regulated and varies dramatically between different nephron segments. The terminal IMCD displays very high rates of transepithelial urea transport enabling delivery of large amounts of urea into the deepest portions of the inner medulla to maintain a high interstitial osmolality for concentrating the urine maximally. Urea in the terminal IMCD is transported by a specific urea transporter that is stimulated by vasopressin and hyperosmolarity. Although the urea transporter has not been cloned, individuals have been identified who lack the urea transporter. Individuals who lacked the Kidd antigen (a minor blood group antigen) also lacked carrier-mediated urea transport in their erythrocytes (and presumably in their kidneys). These same subjects were unable to concentrate their urine above 800 mOsm following overnight water deprivation. This experiment of nature illustrates the critical importance of the urea transporter to concentrating ability in humans. PMID- 8465117 TI - Urinary concentrating mechanism: the role of the inner medulla. PMID- 8465118 TI - Organic osmolytes in the kidney. PMID- 8465119 TI - Ion transport by the collecting duct. PMID- 8465120 TI - The thick ascending limb as a site of renal bicarbonate reabsorption. PMID- 8465121 TI - The role of adenosine in cell-to-cell signaling in the juxtaglomerular apparatus. PMID- 8465122 TI - Impact of methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy in patients with lymph node metastases from transitional cell carcinoma of the lower urinary tract. PMID- 8465123 TI - Urologic cancer research at the National Cancer Institute. PMID- 8465124 TI - Repeat operations after continent urinary reconstruction. PMID- 8465125 TI - The treatment of localized prostate cancer: what are we doing, what do we know, and what should we be doing? The Prostate Patient Outcome Research Team. PMID- 8465126 TI - The use of ex vivo-activated memory T cells (autolymphocyte therapy) in the treatment of metastatic renal cell carcinoma: final results from a randomized, controlled, multisite study. PMID- 8465127 TI - Adoptive immunotherapy of renal cell carcinoma: studies from the Surgery Branch, National Cancer Institute. PMID- 8465128 TI - [What is your diagnosis? Wilson's disease (hepatolenticular degeneration)]. PMID- 8465129 TI - [Chronic polyarthritis: interdisciplinary therapy and reflections on differential diagnosis]. PMID- 8465130 TI - [Early-stage polyarthritis]. AB - Prodromes, articular signs and the different courses in the early stage of rheumatoid arthritis are explained. Atypical forms and variants of rheumatoid arthritis are especially described. These are the following syndromes: palindromic rheumatism, polymyalgic rheumatoid arthritis, Sjogren-syndrome with rheumatoid arthritis, acute symmetric polyarthritis with pitting edema of elderly people. Furthermore the significance of radiological procedures and the investigation for rheumatoid factors in the early stages are discussed. Early diagnosis and consecutively early therapeutic strategies in patients suffering from rheumatoid arthritis are of paramount importance for prognosis. PMID- 8465131 TI - [Low-dose steroids in chronic polyarthritis: a basic therapy?]. AB - The symptomatic and disease-modifying efficacy of low-dose corticosteroids in rheumatoid arthritis is explained. A possible therapeutic effect of low-dose corticosteroids is shown by long-term studies which include radiological evaluation. The safety and side-effects of low-dose corticosteroids are described. Steroid-induced osteoporosis in rheumatoid arthritis is discussed especially based on recently accomplished longitudinal bone density studies. Finally consequences in the management of rheumatoid arthritis are defined. PMID- 8465132 TI - [If I had chronic polyarthritis--current ideas on basic therapy]. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disorder of largely unknown etiology and complex multifactorial pathogenesis. To date, the medical management has been less than optimal and has consisted primarily of drugs that modulate the acute inflammatory process. Over the years a treatment program referred to as the classical therapeutic pyramid has evolved. A new concept and a controversial one in therapy of RA is that already at the time of definitive diagnosis, a more concerted effort towards vigorous treatment using second-line drugs such as methotrexate, should be made. It is very likely that over the next 5 years interventions such as monoclonal antibodies directed against predetermined T-cell subpopulations and anti-cytokines such as TNF-alpha binding proteins will evolve as new concepts in therapy of RA. PMID- 8465133 TI - [Local joint treatment in chronic polyarthritis: intra-articular corticosteroids and radioactive isotopes]. AB - Intrasynovial injection of corticosteroids is currently one of the routine measures in the treatment of patients with rheumatoid arthritis. Crystalline corticosteroid suspensions have proved their value and are effective for approximately one to three weeks. One or two injections can control synovitis for prolonged periods of time. Special attention has to be given to impeccable technique of instillation. However, it must be kept in mind that, within the overall management of rheumatoid arthritis, the intra-articular injection of corticosteroids is a local, palliative and temporary measure. The intrasynovial instillation of radionuclides is used only in selected cases. Therapy of the knee joint is mainly performed with Yttrium-90, less frequently, the interphalangeal joints are treated with Erbium-169. Costs and radiation exposure are low, but a favourable result is only achieved in slightly more than 50 per cent of cases. This review provides a synopsis of the basic concepts and practical applications of intrasynovial corticosteroid and radioisotope injection therapy. PMID- 8465134 TI - [Nutrition and chronic polyarthritis]. AB - Patients suffering from chronic and incurable diseases often try to influence their symptoms by dietary modification. The effect of complete fasting on pain in rheumatoid arthritis is remarkable, but not fully understood. Polyunsaturated fatty-acids, specially omega-3-fatty-acids from fish oil, are significant as precursors of mediators for inflammation. In rare instances food allergy may cause or aggravate arthritis. The actual knowledge is presented in a concentrated form and some practical advice is given. PMID- 8465135 TI - Effectiveness of acoustic reflex threshold criteria in the diagnosis of retrocochlear pathology. AB - This study examines the acoustic reflex threshold criteria, derived from a large group of patients with cochlear hearing loss proposed by Cohen & Prasher (1992), in order to evaluate their effectiveness in differentiating between cochlear and retro-cochlear lesions. This criterion was tested on 63 patients with surgically confirmed cerebello-pontine angle (CPA) lesions. The false results obtained with this and other criteria were compared. The best balance between the false positive and negative results in the cochlear and retrocochlear group is provided by the criterion of any two adjacent test frequencies (proposed in the companion paper) having an upper limit of 105 dB for hearing below 60 dB and 110 dB for hearing over 60 dB. This study has also singled out the interaural difference criterion as the best diagnostic indicator with the lowest false results with only 1 false negative from 63 CPA cases and 3 false positive cases from 61 cochlear lesions with hearing thresholds over 55 dB. PMID- 8465136 TI - Acoustic neuroma and non-tumour retrocochlear patients: audiological features. AB - Seventeen surgically confirmed acoustic neuroma subjects and seventeen radiologically confirmed non-tumour subjects with retrocochlear pathology of unknown aetiology were selected to investigate retrospectively the diagnostic yield of basic audiological test procedures. Puretone audiometry, tympanometry, reflexometry and auditory brainstem response audiometry were used in the identification of acoustic neuromas versus non-tumour retrocochlear disorders. All subjects had been referred originally for neuroaudiological assessment because of suspected acoustic neuroma and had been found to have a range of abnormal ABR findings consistent with retrocochlear pathology. Detailed retrospective analysis of audiological results following surgical and radiological classification showed subject similarities for most parameters of the individual audiological tests for both acoustic neuroma and non-tumour groups. A significant difference was noted, however, between the two clinical populations for the ABR Wave V absolute interaural latency difference parameter. PMID- 8465137 TI - High-frequency tone burst-evoked ABR latency-intensity functions. AB - High-frequency tone burst stimuli (8, 10, 12, and 14 kHz) have been developed and demonstrated to provide reliable and valid auditory brainstem responses (ABRs) in normal-hearing subjects. In this study, latency-intensity functions (LIFs) were determined using these stimuli in 14 normal-hearing individuals. Significant shifts in response latency occurred as a function of stimulus intensity for all tone burst frequencies. For each 10 dB shift in intensity, latency shifts for waves I and V were statistically significant except for one isolated instance. LIF slopes were comparable between frequencies, ranging from 0.020 to 0.030 msec/dB. These normal LIFs for high-frequency tone burst-evoked ABRs suggest the degree of response latency change that might be expected from, for example, progressive hearing loss due to ototoxic insult, although these phenomena may not be directly related. PMID- 8465138 TI - Spontaneous otoacoustic emissions in different racial groups. AB - To determine if there are racial differences in the prevalence of spontaneous otoacoustic emissions (SOAEs), both ears of 20 Negro, 20 Asian and 20 Caucasian subjects were examined for the presence of SOAEs. Within each racial group, equal numbers of normally hearing males and females were tested. Significant differences in the occurrence of SOAEs were found between the three racial groups, with Negroes expressing more SOAEs than Caucasians, and Asians demonstrating an intermediate number of these emissions. In support of previous observations, more emissions were recorded from female than from male ears, and a significant correlation of the number of emissions in the two ears of an individual was also noted. PMID- 8465139 TI - High-frequency air conduction audiometry. Testing of a new low impedance circumaural transducer system in normal young persons. AB - A new circumaural transducer was tested in the frequency range 125 Hz to 20 kHz. The new transducer has a low acoustic impedance and loads the ear closely to free field conditions, thus ensuring that sensitivity to different positions of the transducer around the ear is reduced compared to conventional audiometric headphones. The transducer was tested on 57 individuals (114 ears) in the age range 10 to 20 (median age 17.0 years). The results, showing a fairly good accordance with the ISO standard free-field thresholds values, seem to confirm that the new transducer system loads the ears similarly to free-field conditions. The results were also compared with the threshold values from other high frequency investigations using different transducer systems. In order to verify the reliability of the system, a test-retest was carried out on 12 inexperienced normal individuals (24 ears) (median age 26.5 years; range values from 22 to 44 years). The standard deviations of the test-retest ranged from 2.8dB to 6.6dB. A comparison of these values with the results from other high-frequency test retests is of dubious value, as such retests have often been performed and estimated in different ways. International standards for high-frequency audiometry threshold and international standards for test-retest procedure are needed. The increasing administration of cytotoxic drugs in the treatment of malignant diseases will increase the need for reliable high-frequency audiometry equipment. PMID- 8465140 TI - Performance of assistive listening devices using insertion gain measures. AB - The electroacoustic performance characteristics of seven assistive listening devices (ALDs), that did not need to be coupled with a hearing aid, were measured using real ear insertion gain. The ALDs, which included TV listening systems and personal amplification systems, were measured on ten subjects. Electroacoustic performance of the ALDs varied although there were similarities for different types of devices. Frequency responses were either basically flat or had an emphasis in the low or mid-frequency region. The majority of devices provided negligible amplification when set at or below half volume. Total harmonic distortion was 10% or less for most ALDs. Overall, insertion gain measures were found to be of value in evaluating the effectiveness of this type of amplification device. PMID- 8465141 TI - Factors to consider when in-the-canal hearing instruments are used in aural rehabilitation. AB - The purpose of this investigation was to determine what subjective factors may influence the success of fitting in-the-canal hearing instruments (ITCs). Four different types of ITC were fitted to four matched groups of 20 experienced ITC users. In addition to the subjective experiences of the users, the results were checked using insertion gain (IG) measurements. The results indicate that too sharp sound quality from paper rustle, from running water and from use of kitchen utensils is a common problem that it is important to be aware of. The possibility of maximal venting is of special importance in order to avoid autophony. Feedback may be a problem, especially when maximal venting is necessary. However, for several models of ITC, feedback is, in reality, a minor problem. High cost of batteries may be a problem for persons with ITC using 10/230 batteries. IG measurements indicated that a gain of approximately 0.3 in relation to the hearing losses was preferred. It may be advantageous to choose a model of ITC that has extensive flexibility. PMID- 8465142 TI - ABR latency-intensity function abnormality in the early detection of a cerebellopontine angle tumour: a case study. AB - A case is presented of a 27-year-old male subject with a cerebellopontine angle tumour which was provisionally diagnosed on the basis of the ABR latency intensity function findings and later confirmed by MRI. The patient initially presented with decreased hearing sensitivity, tinnitus and dizziness. The findings of neuroaudiological assessments and radiological examinations are described. The importance of the neuroaudiological test battery, in particular the ABR latency-intensity function, in this case is discussed; and the need for its inclusion for earlier detection and diagnosis of cerebellopontine angle tumours emphasized. PMID- 8465143 TI - The prevalence of perilymphatic hypertension in subjects with tinnitus: a pilot study. AB - This study investigated the prevalence of perilymphatic hypertension (raised perilymphatic pressure) in a population of subjects with tinnitus. A review of the literature showed how changes in perilymphatic pressure could affect tympanic membrane displacement measurements. This review also revealed that perilymphatic hypertension was more likely to occur in young females (less than 45 years) than in other subjects. An experiment was designed to test 32 subjects, who were divided into four groups according to their age and sex. These subjects underwent several routine audiological tests and were then tested with the tympanic membrane measurement system to determine the perilymphatic pressure of both ears. Statistical analysis of the experimental results showed that the young females had raised perilymphatic pressure. This was significantly higher than the perilymphatic pressure of the other test groups and of that of a normal population. The young females also exhibited other symptoms indicative of raised perilymphatic pressure. The raised pressure was thought to be due to an increase in fluid pressure which is more likely to occur in females due to variations in the levels of circulating hormones with menstrual irregularities, pregnancy and the menopause. PMID- 8465144 TI - A model for quality achievement--the NORDKEM protein project. AB - The Nordic protein project demonstrates a model for the process of achieving analytical quality. GOAL: based on use of common reference intervals leading to the quality specifications. Creation of quality: through common high quality calibrator (with IFCC-values) (external factor) and individual trouble-shooting and guidelines (internal factor). Control of quality: with specially designed set of control samples and problem-related evaluation of control data. Establishing common reference intervals: through associated projects. PMID- 8465145 TI - Appropriate sera for calibration and control of specific protein assays. AB - An ultracentrifugation technique is described which makes it possible to prepare protein calibrators and control sera which (i) are stable (more than 8 years documented for nine proteins), (ii) are clear (remains clear for more than 8 years at -80 degrees C), (iii) contain genuine proteins (documented electrophoretically and immunologically), and (iv) are reproducible to prepare (collection and preparation). PMID- 8465146 TI - Development of criteria for the evaluation of reference method values. AB - We present a uniform concept for the requirements of reference methods (RMs) used for target-setting in the German external quality assessment (EQA) scheme. It is proposed that the total allowable error (TAE) of the RMs shall be 0.2 times the acceptance limits in the EQA-scheme. From the TAE are derived limits for maximum RM-bias, RM-imprecision, and the number of measurements. PMID- 8465147 TI - Approaches for providing target values to improve usefulness of external quality assessment scheme. The Spanish experience. AB - The aim of this communication is to highlight the specific aspects of external quality assessment schemes that need to be discussed in a European context: target values, transferability of results and accredit of laboratories. The Spanish situation is presented here. The most reliable way to provide target values is to analyse the control samples by reference methods. However, it is not possible for the majority of national schemes and other approaches are presently used: the verification of consensus means is a practicable solution adopted in Spain. An initial network involving selected routine laboratories has been developed, to attain transferability of results. The traceability of routine calibrators from certified reference materials should be demonstrated. To accredit laboratories for licensing is a complex activity that should consider many aspects, results from the national quality assessment scheme bring one. A scoring system is being used in Spain for guidance, and the complete guidelines are under preparation. PMID- 8465148 TI - Validation of target values in external quality assessment schemes for peptide hormones and tumour markers. AB - Consensus means are tacitly assumed to provide correct target values in many external quality assessment schemes EQAS for peptide hormones and tumour markers. We suggest, however, that such targets should not be used without some evidence of their validity. Comparison of the expected and found increments in the target value on adding known quantities of International Standards to serum pools can provide confirmation of the correctness of target values or, in some cases, identify clearly incorrect targets. Validation of targets is important if EQAS are to stimulate use of correctly calibrated assays, rather than those that simply agree with the most commonly used method(s). PMID- 8465149 TI - The World Health Organization's role and future plans in laboratory standardization. AB - WHO is monitoring health care and the status of health of the population in each of its member states. The statistics provides valuable information for the comparison of the effectiveness of different health systems. As part of its global responsibility on health WHO issues international reference materials (IRMs), assigns international nonproprietary names for therapeutics (INNs), publishes guidelines for good manufacturing practice (GMP) and good laboratory practice (GLP) and, in collaboration with international professional organizations, makes recommendations towards achieving global harmonization of clinical laboratory investigations. PMID- 8465150 TI - A programme for assigning target values for external quality assessment schemes in countries with no authorized reference laboratories. Annex. Experiences with deviating results on Ektachem 700 XR. AB - The use of consensus values in external quality assessment schemes (EQAS) involves several problems and should preferably be replaced with target values obtained by methods of high metrological level. However, such values are difficult to obtain. In the present study we transferred values from the NIST (former NBS) certified reference serum SRM 909 to lyophilized and frozen test sera for various inorganic components using flame absorption or flame emission spectrometry. Enzyme values were assigned by laboratories of members of the former Scandinavian Enzyme Committee. The assignment was based on 2-4 determinations each day through 3 days of experiment. A total of 10 laboratories participated in the work. The results were utilized in a Danish EQAS. One practical concern is the fairly long time (9 months) which was needed for production, collection and compiling all data. To get an impression of how much dry chemistry analysers, e.g, could influence consensus values a Kodak Ektachem 700 XR was studied using lyophilized and frozen sera. The results are reported in the annex. On NIST SRM 909 the values found for sodium(I) were 6% too high even though the findings on frozen human sera were accurate. For aspartate aminotransferase a result three times the target values was found on a human lyophilized serum, while the values on the frozen sera only were slightly too high. PMID- 8465151 TI - Isotope-specific measurements as reference for iron(II+III) in serum in an external quality assessment scheme based on 'real life' samples. PMID- 8465152 TI - Report on a common survey in clinical laboratories in Belgium and in The Netherlands: immunoassays. AB - A common survey for immunoassays was organized for Belgian and Dutch laboratories. We compared the different statistical approaches used in the two schemes; both approaches lead to comparable results. Differences in overall consensus values and overall precision are related to a different selection of kits in the two countries. When analyzing results from users of representative kits in both countries, we found a very good correlation in accuracy but detected also some significant differences in precision for some samples for cortisol and theophylline determinations. For some observed differences there is actually no acceptable explanation. PMID- 8465153 TI - A study of interferences in routine methods for creatinine measurement. AB - A survey was undertaken through the Irish External Quality Assessment Scheme to investigate the extent to which acetoacetate and bilirubin affect routine methods in current use for measurement of serum creatinine. Spiking a sample with 10 mmol/l acetoacetate caused errors ranging from -28% to +22%. The greatest errors were found with end-point Jaffe methods and kinetic Jaffe methods in which there was no time delay between final reagent addition and start of absorbance measurement. A sample with high bilirubin concentration gave apparent creatinine results ranging from zero to 280 mumol/l. Although these interferences are well documented in the literature, this knowledge seems to have had little effect on methods in actual use. PMID- 8465154 TI - External quality assessment scheme for cyclosporin in body fluids. AB - The United Kingdom Cyclosporin Assessment Scheme has over eight years experience in the measurement of cyclosporin and has over 176 participants World wide. The scheme provides a source of reference material which has been assayed by many laboratories and, thereby, provides external quality assessment for the clinical measurement of cyclosporin. The results also allow the direct comparison of the available analytical methodologies. The data presented are a summary of the results received during the period July 1990 to July 1991, inclusive. PMID- 8465155 TI - Results of external quality assessment of analysis of urinary calculi by various methods. PMID- 8465156 TI - External quality assessment of analysis of urinary calculi--a new scheme based mainly on natural concrement materials. PMID- 8465157 TI - Quality assurance for decentralised testing in primary and secondary care. PMID- 8465158 TI - A quality manual for the clinical laboratory including the elements of a quality system. Proposed guidelines. AB - Development of quality manuals is a means for the promotion of quality in clinical laboratories by describing the total quality system. It also provides opportunity of checking whether the quality system is implemented in reality and demonstrates to the hospital administration and the clinicians that the laboratory is committed to quality. The intention of these guidelines is to describe the elements of the quality system for a large clinical laboratory, and to present such a system in the form of a quality manual. The proposed guidelines comply, where relevant, with ISO/IEC guide 25 'General requirements for the technical competence of testing laboratories' and EN 45001 'General criteria for the operation of testing laboratories'. The document may be used as an aid for laboratories wishing to be accredited according to EN 45001, or intending to apply for formal certification of their quality systems, according to ISO 9001 'Quality systems--Model for quality assurance in design/development, production, installation, and servicing' utilizing ISO 9004 'Quality management and quality system elements--guidelines; Part 2 Guidelines for service'. However, information about the minimum requirements for official recognition should be obtained from the particular accreditation or certification body concerned. PMID- 8465159 TI - Quality goals in external quality assessment are best based on biology. PMID- 8465160 TI - Surface areas in ultrasound therapy. Evaluation of seven methods for measuring the treated skin area in physiotherapeutic application of ultrasound. AB - Recent articles on ultrasound (US) do not contain information about precise dosage, thus risking a non-valid conclusion of possible effects. To ensure safer standards in treatment-time, the present study compared 7 methods for the calculation of areas. Measurement by eye had a median relative difference (MRD) from the true reading of 22% (lower quartile (l.q.) = -14%, upper quartile(u.q) = -+46%), with large intraindividual variation, the span of MRD being -46% to +53%. Measuring with the transducer showed a systematic error: MRD was -48% (l.q. = 55%, u.q.= -35%), which is unacceptable. Areas were measured with satisfactory accuracy with 5 methods that require little training and use accessories some of which are inexpensive. Plates with ellipses of known size had a MRD of 0.1%, (l.q. = -3%, u.q. = +2%), while rulers showed MRD of -2%, (l.q. = -0.6%, u.q. = +5%) both on selected material. The most accurate and versatile instruments were a planimeter (MRD = -0.1%; l.q. = -0.6%; u.q. = +0.5%), a Mettler weighing apparatus (MRD = 3%; l.q. = 2%; u.q. = 6%), and a digitizer (MRD = -0.1%; l.q. = 0.4%; u.q. = +0.3%). PMID- 8465161 TI - A three-year follow-up of 195 reported occupational over-exertion injuries. AB - Three years after reporting occupational over-exertion injuries, 181 persons took part in a follow-up study by questionnaire. The objective was to study these persons with respect to their current status of health, well-being and functional capacity and when possible compare collected data to reference data from the "normal population". The studied group reported more physical and psychological symptoms than the reference groups. More than 50% reported difficulties in activities of daily living. Long sick-leaves in the year following the reported injury were associated with remaining pain and low rate of employment. Three years after the injury, 109 persons were in employment. Almost one third of these had changed occupations and now had more varied tasks than at the time of the report. Those whose work loads had been reduced after the injury, did not report less musculoskeletal disorders than others. However, access to social support was positively related with health and psychological well-being. PMID- 8465162 TI - Improvement in gait one year after surgery for knee osteoarthrosis: a comparison between high tibial osteotomy and prosthetic replacement in a prospective randomized study. AB - The aim of this study was to analyse gait improvement one year after high tibial osteotomy and unicompartmental knee arthroplasty in patients with strictly unilateral osteoarthrosis of the medial compartment of the knee. Thirty-six patients, 18 men and 18 women, received a unicompartmental Brigham knee prosthesis and 23 patients, 10 men and 13 women, were operated on with a high tibial osteotomy. Clinical and radiographical assessments were supplemented by a functional test, measurements of thigh muscle torque with a Cybex II dynamometer and analysis on a force plate walkway with electrogoniometers. All patients were assessed prior to, and one year after surgery. Both groups showed overall clinical improvement, as assessed by the British Orthopaedic Association (BOA) score. Pain during walking decreased. The range of knee flexion remained unchanged. The ability to ascend and descend steps improved. The isokinetic thigh muscle torque remained unchanged. In the prosthetic group free walking speed increased from 1.03 to 1.09 m/s (p < 0.001). Step frequency and step length increased (p < 0.001). Single stance phase ratio increased from 0.96 to 0.99 (p < 0.01), indicating a more symmetrical gait. Double stance phase (% gait cycle) of both legs decreased (p < 0.001), indicating a faster transfer of weight during walking. In the osteotomy group, free walking speed did not increase. Step length of the uninvolved leg increased (p < 0.01). Double stance phase of the involved leg decreased (p < 0.001) and double stance phase of the uninvolved leg decreased (p < 0.01). Both groups improved after surgery and there was no difference between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465163 TI - Effect of preoperative physiotherapy in unicompartmental prosthetic knee replacement. AB - The purpose of this study was to analyse the effects of preoperative physiotherapy on pain and function in 39 patients scheduled for unicompartmental prosthetic knee replacement. Nineteen patients were selected at random to receive preoperative physiotherapy. The control group received no preoperative therapy. Evaluations were performed 3 months prior to surgery, immediately before and 3 months after operation. Evaluations included: Clinical assessment, measurements of the knee muscle strength, self-selected walking speed and the oxygen cost of walking. Three months before surgery the patients in both groups had similar types and levels of problems. Before surgery patients who had received physiotherapy showed slight improvements in pain, perceived stability of the knee during walking, and faster self-selected and maximal walking speeds compared to the control group, but were unchanged in muscle strength, ROM, and oxygen cost. Three months after surgery pain was significantly decreased in all patients, however, no significant differences were found between the two groups for any variable except muscle strength. This was unchanged compared to preoperative values for patients of the control group while patients who received preoperative physiotherapy showed a decrease in strength. In summary, this study did not disclose any major benefit from the program of preoperative physiotherapy tested. PMID- 8465164 TI - Vertical ground reaction force feedback to enhance stroke patients' symmetrical body-weight distribution while rising/sitting down. AB - A force platform with an auditory output consisting of two electronic balances was used to reinforce symmetrical body-weight distribution in stroke patients. Forty patients randomly assigned to an experimental group or a control group practised rising and sitting down for 15 min, thrice daily, 5 days a week for 6 weeks. The experimental group but not the control group received ground reaction force feedback through the auditory output. Vertical ground reaction forces under each foot were measured with two force plates. Mean difference in improvement of body weight distribution on the paretic leg was 13.2 +/- 10.7 (M, SD) per cent total body weight in the experimental group and 5.1 +/- 6.7 per cent in the control group in rising (p < 0.01) and 12.7 +/- 7.5 per cent total body weight and 4.6 +/- 6.6 per cent in sitting down tests (p < 0.001). The patients in the experimental group achieved in average close to a symmetrical body-weight distribution while rising and sitting down. Improvements in physical performance and sit-stand tests were greater in the experimental group (p < 0.05 and p < 0.01, respectively). No differences were seen in improvement in performance of activities of daily living. Symmetry in body-weight distribution in rising and sitting down correlated with high scores in physical performance, motor function in rising, and with functional ability. PMID- 8465165 TI - A new nasal mask for nocturnal home ventilation in chronic neuromuscular disorders. AB - A new nasal mask for nocturnal, intermittent positive pressure ventilation was used by patients with symptomatic sleep hypoventilation due to chronic neuromuscular disorders. The custom-fabricated mask is cast in visible light curing acrylic from a plaster model. Air is delivered through plastic tubes cast in the mask. The treatment was introduced through close cooperation between a physiotherapist and a technician. Evaluation was performed after 4-34 months' regular use. The mask was well tolerated. All patients reported comfortable sleep and symptom relief. The effectiveness was confirmed by whole-night measurements of oxygen saturation and end-tidal carbon dioxide. PMID- 8465166 TI - Carcinogenicity of mercury and mercury compounds. AB - Mercury and mercury compounds are widely used in modern society, but only sparse data are available on their carcinogenicity. Methylmercury chloride causes kidney tumors in male mice. Mercury chloride has shown some carcinogenic activity in male rats, but the evidence for female rats and male mice is equivocal. Other mercury compounds and metallic mercury have not been tested adequately in experimental animals. Epidemiologic data are available for chloralkali workers, dentists and dental nurses, and nuclear weapons workers, three groups occupationally exposed to low levels of mercury and its compounds, but those highly exposed in the past, such as miners, or populations which have suffered massive environmental exposure have not been adequately studied. However, the sparse epidemiologic data point toward the possibility of a risk of lung, kidney, and central nervous system tumors. Better data are needed on the carcinogenicity of mercury and mercury compounds in humans and experimental animals. PMID- 8465167 TI - Lung cancer among textile workers in the Prato area of Italy. AB - The association between lung cancer and occupational exposure in the textile industry was investigated in a population-based case-referent study conducted in the Prato area of the province of Florence (Italy) where there is a concentration of textile factories. A complete response to a postal questionnaire was obtained for 207 cases (85.1%) and 440 referents (76.1%). Those who had ever worked in the textile industry had an odds ratio (OR) of 1.45 [95% confidence interval (95% CI) 1.0-2.1]; when nine different textile job titles were considered, an increased OR was observed only for rag sorters (OR 2.2, 95% CI 1.3-3.8) and weavers (OR 1.7, 95% CI 1.1-2.7). Analysis by different "time windows" showed an OR of 3.0 (95% CI 1.6-5.8) for rag sorters at work in the 1950s and an OR of 2.8 (95% CI 1.5-5.0) for weavers at work in the 1970s. This result supports the suggestion of two different carcinogenic exposures in the Prato textile industry (asbestos and mineral oils). PMID- 8465169 TI - Chromosome aberrations in lymphocytes of high-voltage laboratory cable splicers exposed to electromagnetic fields. AB - Thirteen high-voltage laboratory employees and 20 referents participated in a cross-sectional, matched-pairs study of cytogenetic damage. During cable testing the workers were exposed to static, alternating, or pulsed electric and magnetic fields. The alternating magnetic field levels of 50 Hz were 5-10 microT, occasionally much higher. Chromosome aberrations, sister chromatid exchanges, and aneuploidy were studied in peripheral blood lymphocytes. In addition, chromosome aberrations were investigated in lymphocyte cultures treated with hydroxyurea and caffeine, to inhibit deoxyribonucleic acid synthesis and repair. Among seven smoking laboratory employees the mean number of chromosome breaks/200 cells was 2.3, as compared with 0.7 for the job-matched referents. The comparable figures for inhibited cultures were 12.0 versus 6.0. No increase was detected in nonsmokers with either method. The other genetic parameters showed no differences between the exposed workers and the referents. The results support, to some extent, the hypothesis of an increased risk of genotoxic effects among high voltage laboratory workers. PMID- 8465168 TI - Measuring work organization exposure over the life course with a job-exposure matrix. AB - In most epidemiologic studies of occupational stress, work exposure is measured at only one point in time. This article presents a methodology for measuring the intensity and duration of work organization exposure over a lifetime. A job exposure matrix for work organization was developed from data on a random sample (N = 12,084) of the Swedish labor force. The matrix consisted of mean exposure estimates for work control, social support, psychological and physical job demands, and job hazards for 261 occupations. Several validations of the matrix were undertaken. The matrix scores were found to be significantly correlated with individual self-report scores, and a similar increase in chronic disease prevalence with decreasing work control was found for both the matrix and the individual scores. The matrix was applied to occupational history data to construct lifetime exposure profiles. Potential problems in using attribution systems for exposure assessment are discussed. PMID- 8465170 TI - Contribution of the tonic vibration reflex to muscle stress and muscle fatigue. AB - The aim of the investigation was to determine the influence of vibration displacement amplitude (200, 300 microns peak-to-peak), as opposed to acceleration effects at selected frequencies (40, 80, 100, 120, 150, 200 Hz), on a commonly observed but often undesired motor response elicited by local vibratory stimulation, that is, the tonic vibration reflex (TVR). Vibration was applied to the distal tendons of the hand flexor muscles. Changes in the activity of hand flexor and extensor muscles were analyzed as a function of both their initial contraction level (0, 10, 20% of maximal voluntary contraction) and the vibration parameters. The main results indicate that TVR increases with the initial muscle contraction and increases with vibration frequency up to 100-150 Hz but decreases beyond. High-frequency vibration seems to induce less muscle and tendon stress. This result is particularly important for the design of handheld vibrating tools. PMID- 8465171 TI - Shoulder tendinitis and its relation to heavy manual work and exposure to vibration. AB - Three categories of construction industry workers (54 bricklayers, 55 rockblasters, and 98 foremen) were compared in a cross-sectional study. In a structured interview they reported exposure to loads lifted, vibration, and years of manual work. They were also subjected to a clinical investigation including medical history and a detailed shoulder examination. Among the rockblasters 33% had signs of tendinitis in the left and 40% in the right shoulder. Among the bricklayers and foremen 8-17% had signs of shoulder tendinitis. In a multiple logistic regression being a rockblaster compared with being a foreman showed an odds ratio (OR) of 3.33 for left-sided and 1.71 for right-sided shoulder tendinitis. Vibration exposure yielded an OR of 1.84 and 1.66 for the left and right sides, respectively. Vibration exposure or work as a rockblaster seemed to be risk indicators for tendinitis of the shoulders. PMID- 8465172 TI - Bias in risk estimates from variability of exposure to postural load on the back in occupational groups. AB - Variability of exposure can be a source of information bias in studies with exposure assessment based on the use of a sample of workers in each occupational group under study. This paper presents a method to assess the rate of exposure misclassification from the magnitude of overlap of exposure distributions and, consequently, to evaluate the bias to risk estimates in cross-sectional and prospective studies. The percentage of work-time with trunk flexion and rotation was studied in five occupational groups. The rate of misclassification of exposure to trunk flexion and rotation varied from 0.03 to 0.35. Misclassification below 0.10 was found only for occupational groups with at least a 14-fold difference in mean exposure. Higher rates of misclassification can easily bias the risk estimates up to 50%. In the cross-sectional design the odds ratio was more sensitive to bias than the prevalence rate ratio. The estimate of the relative risk in a prospective study design was the least biased. PMID- 8465173 TI - Hepatic metabolism of toluene after gastrointestinal uptake in humans. AB - The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene exposure to 2 mg.min-1 for 3 h the alveolar toluene concentration was 0.07 (range 0-0.11) mg.m-3; exposure to 6 mg.min-1 for 30 min increased the alveolar concentration to 0.9 (range 0.03-2.6) mg.m-3. Ingestion of 0.08, 0.16, and 0.32 g of ethanol per kilogram of body weight during toluene exposure of 2 mg.min-1 increased the alveolar concentration within 10 min, and maximal alveolar concentrations of 5 (SD 3), 24 (SD 11), and 39 (SD 28) mg.m-3 were reached after 30, 60, and 90 min for the three doses, respectively. Hippuric acid excretion was only decreased by an ethanol dose of 0.32 g.kg-1. Very low doses of ethanol inhibit toluene metabolism, and the procedure is sensitive enough to measure metabolic interactions between solvents and other xenobiotics in humans. PMID- 8465174 TI - Solvents in pesticides. AB - Solvents are extensively used in pesticide formulations. This study concerns the solvents notified to the Italian Registry of Pesticides, which has information on approximately 8000 pesticide formulations. Solvents with evidence of carcinogenicity in humans or animals, including benzene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,4-dioxane, and 2-nitropropane, have been notified for use in pesticides. Exposure to such solvents could partly explain some of the reported excesses of leukemia and non-Hodgkin's lymphoma among farmers. PMID- 8465175 TI - The International Commission on Occupational Health. Past and present. PMID- 8465176 TI - Formaldehyde exposure and respiratory cancer--a meta-analysis of the epidemiologic evidence. AB - A recent meta-analysis by Blair and his co-workers stimulated the undertaking of a reanalysis of the epidemiologic evidence of an association between formaldehyde and respiratory cancer. Emphasis was placed on extracting the maximal amount of relevant data from the source studies. In close agreement with the original analysis, the aggregated evidence did not indicate an excess risk or an exposure response gradient for lung cancer. An exposure-response gradient was seen for both sinonasal and nasopharyngeal cancers. The risk for substantial exposure was significantly elevated (odds ratio 1.7 for sinonasal and 2.7 for nasopharyngeal cancer). It is suggested that at least substantial levels of occupational exposure to formaldehyde are associated with a risk of these cancers. The excess risk would be of the order of 100% or more over background rates. PMID- 8465177 TI - [30 years of the Swine Health Service]. AB - The establishment of a Porcine Health Service (PHS) was pioneered in the early sixties. After reviewing the history of the formation of the PHS, a few examples of how it stimulated research in several fields in our two faculties are given. The development of the PHS was noticeably slowed down by yearly recurrent "mysterious" outbreaks of actinobacillosis and especially enzootic pneumonia. Epidemiologic investigations have since shown that the reintroductions of these pathogens can occur by airborne transmission. This information filled the last important gap in the battle against these economically and public health important diseases. Simultaneously it became apparent that enzootic pneumonia and actinobacillosis are not merely herd problems but epizootics which can only be eradicated by means of modern disease control legislation. The question is posed whether or not the PHS, which is potentially a valuable tool in the hands of the state veterinarians, should continue to remain under the control of the producers. PMID- 8465178 TI - [Infection with Bacillus piliformis (Tyzzer's disease) in foals]. AB - Tyzzer's disease, caused by Bacillus piliformis and characterized by a multifocal, necrotizing hepatitis was diagnosed in a 25 days old, male, German warmblood foal. The animal was submitted to the clinic of horses because of colic symptoms and a severe depression. Upon arrival it was comatose, recumbent and showed opisthotonos. Due to a severe, metabolic acidosis and a rapid progression of the disease, the foal was euthanatized. In immediately formalin-fixed tissue samples Bacillus piliformis was detected in the cytoplasma of hepatocytes by different histological techniques (Giemsa stain, silver impregnation technique by Warthin-Starry, immunohistology). This case is discussed within a literature review. PMID- 8465179 TI - [Local and systemic infections with bacteria of group EF-4 in dogs, cats and in a badger: bacteriologic and pathologico-anatomic results]. AB - Bacteria of Group EF-4 were isolated in 7 dogs and in 5 cats from local purulent lesions in areas of natural openings of the head and from bite wounds, from lungs with focal necrotizing pneumonia in 2 additional cats and from internal organs in a badger with septicemia. The organisms grew mostly in pure culture. In conventional biochemical tests, 12 isolates were shown to belong to biovar EF-4a and 3 isolates to EF-4b. Classification as Group EF-4 was confirmed by assimilation tests performed with the commercially available gallery ATB 32 GN. Results of this study indicate that in veterinary medicine, bacteria of Group EF 4 are not only important from an epidemiological point of view, but that they may be more pathogenic for animals than considered hitherto. PMID- 8465180 TI - [Umbilical blood flow relations in pregnancy complications. Part 2. Pathologic index constellations]. AB - In a study comprising a total of 700 pregnant women, umbilical resistance was examined. Measurements were taken at both sides of the cord. A decline in resistance was registered from the fetal abdominal wall to the placental insertion of the vessels. According to a collective of 500 patients with a normal development and outcome of their pregnancies a physiological constellation of the resistance indices could be confirmed. It was taken as a basis for the definition of pathological cases. Different pathologies were related quite clearly to a special (unphysiological) constellation of the indices. PMID- 8465181 TI - [Blood flow in the umbilical artery in maternal hypotonia]. AB - We performed a study in Doppler sonography in pregnant patients with hypotension compared with women in pregnancy with normal blood pressure. The flow was measured in the foetal aorta, the umbilical artery such as in the A. arcuate and A. cerebri media. Low blood pressure is followed by decreased uteroplacental perfusion. That means a haemodynamic danger for the foetus reflected in significantly increased flow parameters. The low central flow indices show a centralisation of the foetal blood circulating system. These findings describe the importance of hypotension as a risk of pregnancy we have to observe carefully. PMID- 8465182 TI - [Apple-Macintosh compatible software for documentation, management and evaluation of ultrasound findings in obstetrics]. AB - The advantage of using a computer to automate routine calculations and print out charts of the obstetrical ultrasound examination is obvious. This report describes a software designed to simplify the documentation and analysis of ultrasound data in obstetrics. The system is easy to use, even for persons with little computer knowledge. The programme was written in FoxBase+/Mac (Fox Software, Inc., USA). FoxBase+/Mac takes full advantage of the easy-to-learn, easy-to-use Macintosh interface and is also very fast. Another advantage of this software is that it can be used in teaching. Non-experienced examinators can double-check the correctness of their scanning planes by observing the ultrasound pictures with the markers indicating the right measurement sites and the lists of standard values of biometrical parameters for the corresponding gestational age on the screen. In routine obstetrical ultrasound examinations it takes less than 5 min to enter the foetal biometry data and print out reports. These reports are informative and easy to interpret. PMID- 8465183 TI - [Ultrasound diagnosis of cervical lymph node tuberculosis]. AB - Lymph node tuberculosis is the most frequent tuberculous manifestation in the otorhinolaryngological area. In 13 patients with histologically verified tuberculous lymphadenitis cervical sonographic examinations revealed characteristic findings. The sonographic features typical for this disease were multiple, enlarged, conglomerating roundish and oval lymph nodes. These lymph nodes were hypoechoic, exhibited dorsal sound amplification and had sharp margins. With caseation, however, there were blurred borders. In cold abscesses an inhomogeneous texture with inhomogeneous shadows was found. Differential diagnosis included non-specific abscess-forming lymphadenitis, lymph node metastases and malignant lymphoma. A tentative diagnosis of cervical lymph node tuberculosis may be made due to the polymorphous sonographic pattern if history and clinical findings are taken into account. A proper histological and microbiological work-up is still essential for confirmation of the sonographic diagnosis. PMID- 8465184 TI - [Prenatal diagnosis of fetal polymicrogyria--case report]. AB - Migration disorders of foetal neurons are rare conditions which are normally diagnosed after birth and may be followed by severe alterations of neurological development. We describe a case of foetal hemilateral polymicrogyria in combination with hemihypoplasia of the brain, the symptoms of which were diagnosed in the 23rd week of pregnancy, leading to termination of pregnancy. To the best of our knowledge, this is the first case report of antenatal diagnosis of this disorder by vaginal sonography. PMID- 8465185 TI - [Early recognition of fetal abnormalities by transvaginal ultrasonography]. AB - Three case reports illustrate situations where transvaginal sonography (TVS) can be important for detecting foetal malformation. In each of these cases a reliable diagnosis was not possible by abdominal ultrasound either because the part of the foetus to be examined lay too low in the pelvis or because it could not be imaged clearly enough due to lack of amniotic fluid. As we would recommend in such cases, diagnosis was then made by TVS. Since the area which can be imaged by TVS is limited mechanically by the anatomical situation, however, it should not be used as the primary method for prenatal screening, whereas in certain selected cases it can provide information not obtainable otherwise. PMID- 8465186 TI - [Acute renal vein thrombosis in children. Early detection with duplex and color coded Doppler ultrasound]. AB - Two children with clinically suspected renal vein thrombosis were evaluated by duplex Doppler sonography and colour flow imaging. Both cases presented unspecific findings with an enlarged kidney and loss of cortico-medullary delineation on gray-scale ultrasound, but an unusual flow pattern with retrograde plateau-like frequency shifts during diastole. No venous signal could be obtained. By colour flow imaging only the main renal artery and its proximal branches could be visualised with a reverberating oscillation of blood flow. In addition, partial thrombosis of inferior vena cava in one patient and iliac vein thrombosis in the other could be demonstrated. Clinical improvement during fibrinolytic therapy in one case and nephrectomy in the other case confirmed the diagnosis. PMID- 8465187 TI - [Intrauterine meconium peritonitis. A rare cause of non-immunologic hydrops fetalis]. AB - A case of foetal non-immune hydrops fetalis is presented. A second gravida was referred to our department at 31 weeks' gestation after normal pregnancy course. Sonography revealed marked foetal ascites as well as a polyhydramnion. Prenatal examinations did not yield a safe diagnosis. The foetal ascites was punctured via a pigtail-catheter that was left in the foetal abdomen. This procedure was supposed to facilitate the development of foetal lungs. At 33 weeks' gestation, after spontaneous rupture of membranes, a boy was spontaneously delivered. Postpartal radiography pointed to bowel perforation. Surgery on the first day of life showed a severe meconium peritonitis following a perforation of the ileum. 22 months after this operation, the boy is physically and mentally well developed. Until now, there is no sign of mucoviscidosis. We believe that early diagnosis, the possibility of prenatal therapy and the close collaboration of disciplines made the survival of this child possible. PMID- 8465188 TI - [Introduction to ultrasonic diagnosis]. PMID- 8465189 TI - [References for prenatal diagnosis of morphological defects including the central nervous system]. AB - Clinical and autopsy records of 209 stillborn and 81 miscarried infants with 484 congenital defects of the central nervous system were analysed. Sets of more than one defect were retrospectively classified by pathogenetic criteria as syndrome, sequence, association and midline defects. Pathogenetic thinking makes the prenatal diagnosis of further defects easier if one has already been diagnosed. Statements regarding the most probable localisation of neural tube defects have been made. PMID- 8465190 TI - Improvements in health care. PMID- 8465191 TI - EMF and cancer. ORAU Panel on Health Effects of Low-Frequency Electric and Magnetic Fields. PMID- 8465192 TI - Drug abuse research. AB - The references in Philip H. Abelson's editorial of 5 February, "Science, technology, and national goals" (p. 743), were incorrect. The first reference should have read, "H. T. Shapiro, The Bridge 22 (no. 3), 14 (1992)." The second reference should have read, "R. E. Gomory, ibid. (no. 2), p. 18." PMID- 8465193 TI - DOD to single out MicroGeneSys vaccine. PMID- 8465194 TI - Researchers win decision on knockout mouse pricing. PMID- 8465195 TI - NSF wins, NIH loses in Clinton's 1994 budget. PMID- 8465196 TI - Huntington's gene finally found. PMID- 8465197 TI - Toxicologists-and snow-descend on New Orleans. PMID- 8465198 TI - DNA repair and transcription: the helicase connection. PMID- 8465199 TI - Cognitive neurophysiology of the motor cortex. AB - A major challenge of current neuroscience is to elucidate the brain mechanisms that underlie cognitive function. There is no doubt that cognitive processing in the brain engages large populations of cells. This article explores the logic of investigating these problems by combining psychological studies in human subjects and neurophysiological studies of neuronal populations in the motor cortex of behaving monkeys. The results obtained show that time-varying psychological processes can be visualized in the time-varying activity of neuronal populations. Moreover, the functional interactions between cells in the motor cortex are very similar to those observed in a massively interconnected artificial network performing the same computation. PMID- 8465200 TI - Molecular mechanism of transcription-repair coupling. AB - Lesions in the transcribed strand block transcription and are repaired more rapidly than lesions in the nontranscribed (coding) strand which do not block RNA polymerase (RNAP). It has been shown previously that in Escherichia coli the mfd (mutation frequency decline) gene is necessary for strand-specific repair. The mfd gene was cloned and sequenced and the Mfd protein was purified and used to reconstitute strand-specific repair in a completely defined system. The mfd gene encodes a protein of 130 kilodaltons and contains the so-called "helicase motifs," a leucine zipper motif, and regions of sequence similarity to UvrB and RecG proteins. The Mfd protein was shown to (i) displace RNAP stalled at a lesion in an adenosine triphosphate-dependent reaction, (ii) bind to the damage recognition subunit (UvrA) of the excision nuclease, and (iii) stimulate the repair of the transcribed strand only when transcription is taking place. Thus, Mfd appears to target the transcribed strand for repair by recognizing a stalled RNAP and actively recruiting the repair enzyme to the transcription blocking lesion as it dissociates the stalled RNAP. PMID- 8465201 TI - DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. AB - The human BTF2 basic transcription factor (also called TFIIH), which is similar to the delta factor in rat and factor b in yeast, is required for class II gene transcription. A strand displacement assay was used to show that highly purified preparation of BTF2 had an adenosine triphosphate-dependent DNA helicase activity, in addition to the previously characterized carboxyl-terminal domain kinase activity. Amino acid sequence analysis of the tryptic digest generated from the 89-kilodalton subunit of BTF2 indicated that this polypeptide corresponded to the ERCC-3 gene product, a presumed helicase implicated in the human DNA excision repair disorders xeroderma pigmentosum and Cockayne's syndrome. These findings suggest that transcription and nucleotide excision repair may share common factors and hence may be considered to be functionally related. PMID- 8465202 TI - Aqueous-phase photochemical formation of peroxides in authentic cloud and fog waters. AB - Gas-to-drop partitioning of hydrogen peroxide and its precursor, the hydroperoxyl radical (HO2.), has been considered the predominant or sole source of hydrogen peroxide in atmospheric water drops. However, atmospheric water can absorb solar ultraviolet radiation, which initiates the photoformation of peroxides (primarily hydrogen peroxide). Measurements of peroxide photoformation rates in authentic atmospheric water samples demonstrate that aqueous-phase photochemical reactions are a significant, and in some cases dominant, source of hydrogen peroxide to cloud and fog drops. This additional source could significantly change the current understanding, and hence, the models, of sulfuric acid deposition because hydrogen peroxide is the limiting reagent in the dominant pathway for the oxidation of sulfur dioxide to sulfuric acid in the troposphere over eastern North America. PMID- 8465203 TI - Altered growth of human colon cancer cell lines disrupted at activated Ki-ras. AB - Point mutations that activate the Ki-ras proto-oncogene are presented in about 50 percent of human colorectal tumors. To study the functional significance of these mutations, the activated Ki-ras genes in two human colon carcinoma cell lines, DLD-1 and HCT 116, were disrupted by homologous recombination. Compared with parental cells, cells disrupted at the activated Ki-ras gene were morphologically altered, lost the capacity for anchorage-independent growth, grew more slowly both in vitro and in nude mice, and showed reduced expression of c-myc. Thus, the activated Ki-ras gene plays a key role in colorectal tumorigenesis through altered cell differentiation and cell growth. PMID- 8465204 TI - Magnetic resonance imaging of the scrotum. PMID- 8465205 TI - Case of the season. Intussusception. PMID- 8465206 TI - The role of nuclear medicine in the evaluation of the male genital tract. AB - Scintigraphic techniques for evaluation of impotence are still evolving. Blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. A non-imaging version of this test may represent a simple and cost-effective alternative. Washout of intracavernosal xenon during erection seems the most useful method of testing venous integrity. Washout using Tc-RBC may emerge as a convenient alternative to the more technically difficult xenon examinations. Development of more effective pharmacologic stimuli may further improve the utility of this quantitative and physiologic examination. PMID- 8465207 TI - Duplex Doppler ultrasonography: noninvasive assessment of penile anatomy and function. PMID- 8465208 TI - Ultrasound of the scrotum. PMID- 8465209 TI - Magnetic resonance imaging of the prostate. PMID- 8465210 TI - Imaging of the seminal vesicles. PMID- 8465211 TI - Multiple cerebral aneurysms in patients with sickle cell disease. AB - Patients with sickle cell disease appear to have a high incidence of cerebral aneurysm. These aneurysms are not associated with the usual risk factors of hypertension, renal disease, or connective tissue disease. We present two recent cases of patients with sickle cell disease and multiple cerebral aneurysms, review the literature on the association between sickle cell disease and cerebral aneurysms, and discuss a mechanism by which sickle cell disease may lead to the formation of cerebral aneurysms. PMID- 8465212 TI - Expectations and needs of persons with family members in an intensive care unit as opposed to a general ward. AB - The positive effect of family support on the outcome from serious illness that requires intensive care has been recognized by clinicians for decades. We have all seen that family visitation and an intensive care environment more similar to that of a general ward (sunlight, radio, television) can benefit patients with psychosis related to intensive care. The severity of illness of the individual patient exerts a powerful stress on the family unit, but it has been difficult to measure this effect. We used a 40-question family needs survey with a degree of importance scale to compare the intensive care unit (ICU) with the general ward in terms of impact on the family. Five needs were found to discriminate these two environments. The family members of patients in an ICU considered it very important (1) for staff to give directions on what to do at the bedside, (2) to receive more support from their own family unit, (3) to have a place to be alone as a family unit in the hospital, (4) to be informed in advance of any transfer plan, and (5) to have flexibility in the time allowed for visitation. Family members are willing to accept decreased visitation time if the physicians and nurses can equate this decrease with the complexity of care in the ICU. The results of this survey have helped us modify and individualize our approach based on family expectations especially when patients are transferred from the general ward to the ICU or from the ICU to the ward. PMID- 8465213 TI - The Texas Breast Screening Project: Part I. Mammographic and clinical results. AB - The 1987 Texas Breast Screening Project was designed to educate women about the benefits and safety of mammographic screening. During the 2-week promotion, 109,339 women called toll-free telephone numbers to inquire about the program, and 64,459 (65%) of 99,650 eligible callers had $50 mammograms at 306 participating community radiology centers. Biopsies were obtained for 1,122 women (1.7% of those screened), and the ratio of benign to malignant biopsy results was 4.2:1. Among the women having biopsies, 214 cancers were found (3.3 cancers per 1,000 women screened). Forty-seven percent of the tumors were not palpable, 80% were smaller than 2 cm, and 72% were clinicopathologic stage 0 or I. These results show that women will respond to an invitation to attend mammographic screening, and that community radiology centers can detect large numbers of early, curable breast cancers. PMID- 8465215 TI - Incentives for physicians to treat HIV-seropositive patients: results of a statewide survey. AB - We asked primary care physicians in South Carolina about their knowledge, attitudes, and beliefs regarding patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and the services they provide for these patients. In support of an effort to develop more effective state policies regarding HIV/AIDS, the survey focused on conditions under which physicians would provide additional services for such patients; 597 of 900 physicians (66%) responded. Among responding physicians, 40% had not seen a patient with HIV infection/AIDS during the past year and 50% had seen only one to nine. Respondents identified lack of specialty backup support, insufficient clinical knowledge, and lack of available community services as the major barriers to providing care for these patients. Gaps in their knowledge included state and federal policies, available community resources, and clinical issues. Respondents said they would provide additional services if they had specialty backup (54%), better community and social support services (50%), additional training (46%), and limited liability (44%). We concluded that policy changes in these areas could expand access to care for HIV/AIDS patients in South Carolina. PMID- 8465214 TI - The Texas Breast Screening Project: Part II. Demographics, risk profiles, and health practices of participants. AB - More than 36,000 of the 64,459 women who had $50 mammograms after a media campaign in 1987 completed a demographic and risk factor questionnaire. The screened women were young and well educated with high annual incomes. Only 32% had had mammograms before 1987. Most women reported that high cost and lack of referral for mammography by their physicians were their reasons for not being screened previously. Publicity promoting the project and the lower cost for mammography were the features of the project that attracted participants. Population-based telephone surveys before and after the project showed a change in attitudes about breast cancer screening. The model used for recruitment in this project can improve compliance with recommendations for regular mammographic screening if charges for screening are reduced. Additional efforts are needed to attract minorities and poor or elderly women to regular breast screening. PMID- 8465216 TI - Conservative alternatives in the management of early adenocarcinoma of the rectum. AB - The majority of patients with adenocarcinoma of the rectum are treated with radical surgical procedures. Lesions located in the distal third of the rectum are usually treated by abdominoperineal resection, and those situated in the proximal portion of the rectum are treated by low-anterior resection. Relatively small, moderately or well differentiated lesions have a low risk of lymph node metastasis, and are therefore amenable to conservative (ie, rectum-sparing) procedures. Conservative management options consist of transrectal excision, transrectal excision and preoperative or postoperative radiotherapy, endocavitary contact radiotherapy, and interstitial therapy. Discussion of these options, the experience at the University of Florida with two of these options, and review of the literature follow. PMID- 8465217 TI - Pregnant patients in the intensive care unit: a descriptive analysis. AB - We present a descriptive analysis of experience with pregnant women in the intensive care units at a tertiary hospital. During the period from 1983 through 1990, 38 women were admitted to our intensive care units during their pregnancy or within 2 weeks postpartum. This was a rate of 1 per 400 pregnant patients. The mean age of these 38 women was 25 years; 68% of them were white and 32% were primigravidas. Nineteen of the 38 women were mechanically ventilated. Twelve women were admitted for hypertensive disease and 10 for adult respiratory distress syndrome. Maternal mortality was 18% (7/38). Follow-up was available for 33 women. The fetal and neonatal loss rate in this group was 4 of 33 pregnancies. In this case series of 38 very ill women, it was apparent that a team approach of obstetricians, anesthesiologists, and intensive care workers provided optimal management for the mother and child. PMID- 8465218 TI - Doppler ultrasonography of the umbilical cord in complicated pregnancies. AB - Ninety-two gravid women had Doppler insonation of the umbilical cord after diagnosis of various pregnancy complications. Calculations of the systolic diastolic (S/D) ratio were plotted against a nomogram of values developed at the Hospital of the University of Pennsylvania. An S/D ratio greater than the 95th percentile for gestational age correctly predicted 58% of women who became preeclamptic and 61% of infants who were small for gestational age (SGA). Of those fetuses with an elevated S/D ratio, 42% suffered fetal distress as defined by an abnormal fetal heart rate tracing, a 1- or 5-minute Apgar score less than 5 or 7, respectively, or a cord blood pH determination less than 7.20; 60% required operative delivery; and 49% stayed in the hospital longer than 5 days or were admitted to the Neonatal Intensive Care Unit (NICU). All these values are significantly greater than those obtained in a control group of uncomplicated pregnancies or a group of women with similar pregnancies, but with normal measurements of the umbilical artery S/D ratio. Moreover, 69% of abnormally elevated umbilical artery S/D ratios were detected at or before 30 weeks' gestation. Calculation of an S/D ratio of the umbilical cord greater than the 95th percentile for gestational age is an early and sensitive predictor of poor perinatal outcome. PMID- 8465219 TI - Management of borderline tumors of the ovary. AB - We retrospectively reviewed the cases of 51 patients with borderline ovarian tumors seen over a 9-year period. Half of these tumors were manifested by abdominal distention and pain; the remainder were found incidentally at the time of surgery planned for other reasons. Overall survival is excellent, but proper surgical staging reveals that approximately 15% of patients have metastasis beyond the ovaries, most commonly to the omentum, peritoneum, and retroperitoneal lymph nodes. PMID- 8465221 TI - Personality disorders: an overview for the physician. AB - Personality disorders are common clinical syndromes that often go unrecognized in medical practice. Because patients with personality disorders receive care in all clinical settings, physicians could profit from a heightened awareness of the personality psychopathology of their patients and its impact on medical practice. Personality traits are universal and describe the "normal" range of behavior, while personality disorders are characterized by enduring maladaptive patterns. The etiology of personality disorders is multifactorial. Physician awareness of the multiple manifestations of specific personality disorders is helpful in matching the proper interventions to appropriate patients. Although management is symptomatically palliative rather than curative, physicians and patients alike can benefit from appropriate recognition and treatment of personality disorders. PMID- 8465220 TI - Superiority of amniotic fluid index over amniotic fluid pocket measurement for predicting bad fetal outcome. AB - Semiquantitative amniotic fluid volume (AFV) determination is a component of the fetal biophysical profile (BPP). To assess decreased AVF we did BPPs of 174 fetuses within 1 week of delivery. Two methods were used: measurement of the single largest vertical pocket (oligohydramnios = depth < 1 cm) and the four quadrant amniotic fluid index (AFI) (oligohydramnios = AFI < or = 5 cm). AFV, as determined by each method, was related to measures of fetal outcome (perinatal mortality, fetal distress, Apgar score, meconium-stained amniotic fluid, and intrauterine growth retardation [IUGR]). The AFI was more sensitive in predicting mortality (87.5%) and the following measures of perinatal morbidity: low 5-minute Apgar score (88.8%), fetal distress during labor (86.6%), meconium-stained amniotic fluid (63.6%), and the presence of IUGR (79.4%). The sensitivity of amniotic fluid pocket measurement of < 1 cm was 75%, 72.2%, 66.6%, 47.7%, and 55.8%, respectively, for the same measures. Using the AFI instead of a single pocket measurement in BPP assessment increased the sensitivity and positive predictive value of the BPP from 64.7% to 76.4% and from 45.8% to 68.4%, respectively. Our data suggest that qualitative AFV measurement using the AFI is superior to that of the single largest pocket in multiple component fetal biophysical testing. PMID- 8465222 TI - Deep venous thrombosis. AB - Deep venous thrombosis is a common problem in clinical medicine and the focus of research from many perspectives, including incidence, identification of risk factors, diagnosis, treatment, and sequelae. Because of their frequency and resultant morbidity and mortality, these thromboses demand our continued respect and necessitate vigilance in continuing education regarding new developments in diagnosis and management. PMID- 8465223 TI - Moonlighting in a university surgical training program. AB - The impact of house officer moonlighting on training performance was assessed through a faculty questionnaire and house officer survey distributed in the Department of Surgery at Tulane University School of Medicine. Responses were obtained from 30 house officers and 15 faculty members. Most house officers who moonlighted did so one or two times each month; most were employed in emergency departments. Yearly earnings from moonlighting averaged approximately $10,000. Although many house officers were in debt from medical school, debt was not the primary reason for moonlighting. Many faculty members disapproved of moonlighting, but agreed to monitoring by clinical performance and American Board of Surgery In-Training Examination. A statistically significant relationship was found between yearly income from moonlighting and decreasing scores on the American Board of Surgery In-Training Examination. PMID- 8465224 TI - Juvenile laryngeal papillomatosis: a new complication. AB - Extension of juvenile papillomas to the lung parenchyma is unusual. When it occurs, the patient's prognosis worsens because these lesions destroy lung tissue as they grow. Respiratory complications eventually occur in the presence of multiple nodular and cystic lesions due to the attendant parenchymal destruction. We have observed that pneumothorax can occur after the development of cystic pneumatoceles, presumably from the ball valve effect of a nodular lesion (Fig 3). PMID- 8465225 TI - Cryptococcal pneumonia occurring as an infiltrative mass simulating carcinoma in an immunocompetent host: plain film, CT, and MRI findings. AB - Cryptococcosis, a potentially fatal pulmonary infection, rarely occurs in advanced form in immunocompetent individuals. Radiographic findings are variable and include single and multiple mass-like infiltrates, nodules, and segmental infiltrates. MRI manifestations of pulmonary cryptococcosis have not been reported previously. We have compared MRI, CT, and plain film radiographic findings in a case of multisegmental cryptococcal pneumonia occurring as a mass simulating carcinoma in an immunocompetent individual; we have also discussed the differential radiographic evaluation of pulmonary cryptococcosis. PMID- 8465226 TI - Holt-Oram syndrome associated with hypoplastic peripheral vasculature and midsystolic click. AB - Holt-Oram syndrome is a rare, autosomal dominant syndrome characterized by upper extremity skeletal abnormalities and cardiac defects. The most common skeletal anomalies involve the thumbs and range from minor radiographic abnormalities to phocomelia. The most common cardiovascular abnormality is ostium secundum ASD, followed by ventriculo-septal defect and ostium primum ASD. MVP and hypoplastic peripheral vasculature of the upper extremities have been reported only rarely. We have reported the case of a patient with HOS who has both hypoplastic peripheral upper extremity vasculature and evidence of MVP. PMID- 8465227 TI - Unusual calcified goiter associated with increased iodoprotein in serum. AB - For 30 years we have followed the case of a euthyroid patient who had a goiter diagnosed at age 15. It was originally diffuse and did not shrink during treatment, first with desiccated thyroid extract and then with triiodothyronine. After treatment was stopped, the goiter gradually became nodular and calcified when the patient was in her late teens or early 20s; it then shrank. She remains clinically and chemically euthyroid, with a calcified, multinodular goiter and persistent elevation of the serum PBI concentration which, early in the course of the disease was shown to include a substantial fraction of butanol-insoluble iodine. In a euthyroid patient, the association of an elevated serum PBI concentration (with an abnormally large butanol-insoluble iodine fraction) with a diffuse goiter that became nodular and calcified may be unique. PMID- 8465228 TI - Cicatricial pemphigoid. AB - This case of CP is of interest because of its "not-so-benign" course in this patient, its unusual immunofluorescence patterns, and the need for a complex therapeutic regimen to achieve control. This patient had severe ocular; laryngeal, and oropharyngeal involvement leading to visual problems, hoarseness, and marked weight loss and dehydration. He also had anemia thought to be partially related to dapsone use. We believe the side effects of dapsone, combined with fluid retention due to prednisone therapy, contributed to cardiac failure. The diagnosis of CP is usually established by correlation of clinical findings with immunofluorescence studies. However, indirect immunofluorescence may show strong intercellular antibody binding in the epidermis (ie, pemphigus like antibodies). Treatment alternatives for patients with CP who have adverse reactions to, or no significant benefit from, conventional agents such as dapsone or prednisone may include immunosuppressive agents such as azathioprine or cyclophosphamide. As this case demonstrates, care of patients having CP involves a cooperative effort from a number of different specialties, including dermatology, primary care, ophthalmology, and otolaryngology. PMID- 8465229 TI - Dilated cardiomyopathy as an early and rapidly progressive presentation in a woman with acquired immunodeficiency syndrome. AB - Cardiac disease associated with AIDS is common and is manifested by a variety of lesions. With the advances in therapy for common opportunistic infections, AIDS associated cardiac abnormalities will play a prominent role in morbidity and mortality. This case illustrates a rapidly progressive and fetal course of AIDS associated dilated cardiomyopathy in an HIV-infected young woman in relatively stable condition. It is important to be aware of the cardiac manifestations of AIDS so that one can undertake a rational diagnostic and therapeutic approach. PMID- 8465230 TI - Pustulotic arthro-osteitis: a cause of atypical chest pain and a new arthritic syndrome. AB - We have described a 38-year-old white American woman who had a 7-year history of pain in the left anterior chest, neck, right wrist, and buttocks. The pain fluctuated in severity and appeared to coincide with worsening of her skin condition, palmoplantar pustulosis (PPP). She manifested the typical skeletal features of an arthritic condition referred to as pustulotic arthro-osteitis, which is frequently associated with the characteristic rash of PPP. This is an infrequently described disorder in the United States, possibly reflecting lack of familiarity or confusion with related disorders. PMID- 8465231 TI - Gaucher's disease associated with chronic lymphocytic leukemia. AB - To date, only five cases of associated Gaucher's disease and chronic lymphocytic leukemia (CLL) have been reported in the world literature. The exact relationship of the two diseases to one another has been puzzling, and Gaucher's disease has been viewed as both a cause of and an epiphenomenon to chronic lymphocytic leukemia. In this case, because of the temporal relationship of the two conditions and the confirmation of Gaucher's disease by both histochemical means and electron microscopy, we believe that a cause/effect interaction may exist. However, the exact mechanism by which this may occur is, as yet, speculative. PMID- 8465232 TI - Severe bruxism in a demented patient. PMID- 8465233 TI - Granular cell myoblastoma involving multiple organs. AB - We have described a rare case of multifocal granular cell myoblastoma affecting respiratory and hepatobiliary tracts in a young woman. The patient had successful tracheal resection and biliary stent placement to alleviate symptoms. Long-term follow-up will clarify the true nature of the disease. PMID- 8465234 TI - On 60 years of observation and interpretation in one disease: a comment on the career of L. W. Diggs, MD. PMID- 8465235 TI - Does social deprivation during gestation and early life predispose to later schizophrenia? AB - We employed a case-control study design to investigate whether schizophrenic patients differed from non-psychotic psychiatric patients in terms of place of birth and paternal occupation. "Cases" were first-contact schizophrenic patients ascertained from the Camberwell Cumulative Psychiatric Case Register. "Controls" were the next (non-psychotic) patient on the Register matched for age and sex. In comparison with controls, cases were more likely to have: (1) been born in the deprived inner-city Camberwell catchment area (odds ratio 2.3), and (2) had fathers who had "manual" as opposed to "non-manual" occupations (odds ratio 2.1). The results were compatible with the notion that socio-economic deprivation during gestation and early life predisposes to later schizophrenia. PMID- 8465236 TI - The needs of high and low expressed emotion families: a normative approach. AB - Comparison of the needs and characteristics of relatives classified as high and low expressed emotion (EE) across a range of measures including social functioning and indices of stress and family burden revealed that high EE relatives reported higher levels of disturbed behaviour, subjective burden, and perceived themselves as coping less effectively. Individuals from high-EE households were more impaired in terms of social functioning, particularly in terms of independence and interpersonal functioning. No difference in overall knowledge about schizophrenia was observed between high and low EE relatives, although high EE relatives possessed more information about hospital procedures. Analysis of needs assessment data, based on a normative approach to need, revealed that two-thirds of high EE relatives, as against one-third of low EE relatives had high needs in at least one or more of the following five areas: knowledge about schizophrenia, subjective burden, personal stress, behavioural disturbance and perceived coping. No low EE relative had high needs on all five criteria. The implications of the results for the meaning and genesis of EE and for service provision are considered. PMID- 8465237 TI - Utilization patterns of community mental health services by newly referred patients. AB - The present study compared the pattern of service utilization over a 1-year period, of 349 newly referred adult patients to the four community mental health clinics in Jerusalem. Treatment in these clinics is provided free of charge and there are no limits on length of treatment. Irrespective of patient diagnosis and clinic setting, the percentage of patients remaining in contact with the clinics declined sharply during the first 3 months, and after 6 months stabilized to around 25-40%. However, among patients with nonmajor psychiatric disorders, inter clinic variation in compliance with treatment was observed. In clinics with a long-term psychotherapeutic orientation, a larger proportion of patients was referred to other services following intake, and a larger proportion of patients dropped out of treatment. In these clinics, more patients were placed on waiting lists before beginning treatment, and the drop-out rate among these patients was significantly higher than that of patients in treatment. The implications of these results for treatment policy in public services are discussed. PMID- 8465239 TI - Psychiatric morbidity in social workers' clients. A comparison between an inner city area and a small town. AB - The rate of psychiatric disorder in a social services sample in a small town was compared to the rate in an inner-city sample. Nearly 40% of respondents in the small town had a positive General Health Questionnaire score and 37% had case status (ID greater than 5) on the Present State Examination. Most of these were cases of neurotic depression and were generally recognised as such by the social workers. The type of intervention undertaken by social workers differed in the two settings. Small-town social workers were more likely to offer advice, guidance, exploration and mobilisation of resources. The small-town social workers were more likely to have success in helping their clients with problems of social isolation and marital disharmony than were their inner-city counterparts. Mental illness problems, however, showed less improvement than in the inner-city sample, with over one-third of the small-town cases remaining unwell throughout the 12-month follow-up. Both previous psychiatric history and current depression were indicators of a poor outcome. The present findings provide further support for the argument that unless there is close collaboration between social workers, the medical profession, and health care teams, people who present their problems to social services are unlikely to have their mental health problems addressed adequately. PMID- 8465238 TI - Suicide in Hong Kong 1971-1990: age trend, sex ratio, and method of suicide. AB - This study gives an overview of the suicide rates in Hong Kong in the last 2 decades (1971-1990). It was found that the average suicide rate for the whole population was 11.3 per 100,000 population and it has been quite steady in recent years. The male and female adolescent (age-group 10-24 years) suicide rates were approximately the same, while the ratio of the overall male to female rate was 1.3:1. This indicated a relatively high female rate as compared with other countries. An examination of the suicide rates for various age-groups showed that the rate increased with age. The adolescent suicide rate was not particularly high (4.7 per 100,000 population for the age-group 10-24 years), but that for the elderly was 4-5 times the overall rate (49.5 per 100,000 population for those aged over 70 years). As regards the method of suicide, jumping from a height and hanging predominated in all age-groups. These methods were in great contrast to those used in other countries. PMID- 8465240 TI - Physical morbidity in older people with moderate, severe and profound mental handicap, and its relation to psychiatric morbidity. AB - This report describes a study of physical health problems and their relation to psychiatric morbidity in a community sample of 105 people with severe mental handicap and over the age of 50 years from a Metropolitan Borough. An extensive outreach exercise ensured that almost 100% of people fulfilling the age and ability criteria were included in the study. All the physical and mental health assessments were carried out by a psychiatrist at senior registrar level. Physical assessments used a combination of physical examination and access to the subject's medical records. Results showed that, with minor exceptions, the physical health of the handicapped population was no worse than that of controls. Contrary to expectation, no relationship was demonstrated between physical and psychiatric morbidity. However, this may be due to the greater difficulty in identifying psychiatric morbidity in people who are more severely handicapped. Since physical health problems increase with level of handicap, the potential relation between physical and mental health is masked. PMID- 8465241 TI - A community survey of psychotropic drug consumption in South Verona: prevalence and associated variables. AB - A cross-sectional community survey was undertaken to investigate the pattern of psychotropic drug consumption in 453 community residents of South Verona. Overall, 15.0% of the subjects were taking psychotropics (benzodiazepines 13.5%, antidepressants 2.2%, neuroleptics 1.1%). Prevalence was higher in females (20.0%), in those over 45 years (25%), in high General Health Questionnaire (GHQ) scorers (26.2%), and in subjects with physical ill-health (27.0%), with social problems (20.0%), with distressing events (22.0%) and with alcohol abuse (32.3%). Logistic regression analysis showed that age, sex, GHQ score, physical ill-health and life events were all significantly and independently associated with psychotropic drug consumption. PMID- 8465242 TI - The sectorisation of psychiatric services in England and Wales. AB - Sectorisation is the establishment of small geographical catchment areas with dedicated mental health staff providing services to all patients living in the area. This model of care became very widespread during the 1980s in England and Wales: 81% of District Health Authorities responding to a postal questionnaire in this study were sectorised, and around three-quarters of these had become sectorised after 1980. However, this has occurred without central planning and with very little evaluation. Important questions remain to be answered about its efficacy for the severely mentally ill, about the provision of 24-h cover in a sectorised service, and about which services are appropriately provided at a sectorised and which at a centralised level. PMID- 8465243 TI - [Frequency of x-ray and alternative studies]. PMID- 8465244 TI - [Radiation exposure in x-ray diagnosis and dose levels as a basic risk in present day radiation protection discussions]. PMID- 8465245 TI - [Computed tomography of the gastrointestinal tract using water as contrast medium]. PMID- 8465246 TI - [Magnetic resonance tomographic changes in intracranial and spinal tumors following radiotherapy]. PMID- 8465247 TI - [Thymic hyperplasia as a potential differential diagnosis of mediastinal space occupying lesions following cytostatic therapy]. PMID- 8465248 TI - [Gynecologic brachytherapy--from low-dose-rate to high-tech]. AB - The transition from low-dose-rate (LDR) brachytherapy to high-dose-rate (HDR) afterloading treatment is in progress in most centres of radiation therapy. First reports of studies comparing HDR and LDR treatment in cervix cancer demonstrate nearly equal local control. In our own investigations on 319 patients with primary irradiated carcinoma of the cervix (125 HDR/194 LDR) we found the following control rates: Stage FIGO I 95.4%/82.9% (HDR versus LDR), stage FIGO II 71.4%/73.7%, stage FIGO III 57.9%/38.5%. The results are not significant. The side effects--scored after EORT/RTOG criteria--showed no significant differences between both therapies for serious radiogenic late effects on intestine, bladder and vagina. The study and findings from the literature confirm the advantage of the HDR-procedure for patient and radiooncologist and for radiation protection showing at least the same results as in the LDR-area. As for radiobiological point of view it is important to consider that the use of fractionation in the HDR-treatment is essential for the sparing of normal tissues and therefore a greater number of small fractionation doses in the brachytherapy should be desirable too. On the other hand the rules, which are true for fractionated percutaneous irradiation therapy (overall treatment time as short as possible to avoid repopulation of tumor cells) should be taken into consideration in combined brachy-teletherapy regime in gynecologic tumors. The first step in this direction may be accelerated regime with a daily application of both treatment procedures. The central blocking of the brachytherapy region from the whole percutaneous treatment target volume should be critically reflected, especially in the case of advanced tumors. PMID- 8465249 TI - [Adjuvant radiotherapy following radical prostatectomy--results, acute and late toxicity]. AB - Between 1975 and 1987, 53 patients with radical retropubic prostatectomy for adenocarcinoma of the prostate (pathological stage C or D1) underwent adjuvant radiotherapy. 26 of these patients additionally underwent subcapsular orchiectomy. Radiation therapy was given to 45 patients as 40 to 50 Gy to the pelvic lymph nodes followed by a boost to the tumor bed to a total of 64 to 70 Gy. Only five of the 45 patients received treatment to prostate and pelvis developed progression, whereas four out of eight patients who were irradiated to the prostate alone showed progression (p < 0.01). The five- and ten-year disease free survival rates of 33 patients with stage C tumors were 91% and 83%, the local control rate 97% and 94%. 20 patients with stage D1 carcinoma showed a five year disease-free survival of 79% and a local control rate of 95%. 25/26 patients with subcapsular orchiectomy are living disease-free, 8/27 patients without hormonal manipulation had a progression of disease (p < 0.05). All 13 patients with well or moderate differentiated tumor are alive without evidence of disease, 9/40 patients with poor differentiated carcinoma have shown tumor progression (p < 0.05). Compared to published results, our data suggest, that adjuvant radiotherapy can decrease local recurrence and probably increase disease-free survival in stage C and D1 carcinoma of the prostate. PMID- 8465250 TI - [Three-dimensional radiation planning. Studies on clinical integration]. AB - The routine use of three-dimensional treatment planning was evaluated in a clinical project funded by the German Krebshilfe at the Radiological Department of the University of Heidelberg. 166 patients entered the prospective study within 14 months, 155 of them were treated according to the 3D-plans. More than 50% of the patients had thoracic tumors, followed by pelvic tumors. One medicine physicist and one specially trained technician performed the treatment planning. The target volumes were contoured in the CT slices at the planning computer by the responsible radiotherapists. A mean of 6.5 hours per patient was necessary for all planning procedures, however, this time consumption shows a trend toward less time of only four hours including about ten optimization steps. Meanwhile approximately 20 to 30% of all computer assisted planning are performed in 3D, corresponding to about one plan per day. The achieved time consumption is a clinically accepted quantity, that allows the introduction of 3D-planning into clinical routine. PMID- 8465251 TI - Radiation therapy verification in brachytherapy combining iron sulphate gel irradiation and magnetic resonance imaging (MRI). AB - We developed a verification method that allows the three-dimensional qualitative delineation of the dose inside an applicator during intracavitary brachytherapy using MRI of dose-dependent changes of iron sulphate. In addition to computer calculations, the verification of the dose distribution is depicted now within the applicator. Therefore one can get a qualitative information about the relative position of the applicator according to the tumor volume and the desired brachytherapy radiation volume. PMID- 8465252 TI - [The physical and technical outlook for neutron therapy in Germany]. AB - All five fast neutron therapy centres in Germany use low energy cyclotrons or neutron generators and are, therefore, at the low energy end of the 21 neutron therapy facilities presently in use worldwide. The depth dose characteristics are worse than for 60Co gamma rays, the absorbed dose rate is too low and the treatment is technically restricted because of the lack of those modern features like multileaf collimators and full gantry rotation that are available with modern linear accelerators. A survey of the statistical and methodical data on the neutron treatment in Germany is presented. To avoid masking the potential biological benefits of high LET neutron irradiation by the use of suboptimal equipment and to utilise the real therapeutical benefit for specific tumor types, the German neutron therapy centres urgently need modernization of their outdated facilities. Specific recommendations of how to meet the requirements of modern neutron therapy are given. PMID- 8465253 TI - Quality assurance in radiotherapy in Germany (as far as distinctions may occur compared to Britain). AB - The distinction between radiation protection and quality assurance in radiotherapy plays an important role. Together with the chronology of legal regulations for both subjects they are discussed subsequently for better understanding of the German position. A survey on actual technical regulations for safety and quality in radiotherapy by DIN-IEC and DIN standards is given with special attention to the connection of legal and technical regulations, the structure of the DIN committee for radiology and of its standards. Concepts of requirements and test methods for quality assurance are demonstrated for medical electron accelerators, especially the significance of performance values, the reliability of test methods, the volume of test conditions, the interpretation of test results, and the responsibility for test executions. PMID- 8465254 TI - Cell kinetic analysis after irradiation in L929- and LLC-MK2-cells by a BrdU/DNA assay. AB - Exponentially growing L929- and LLC-MK2-cells were X-irradiated in vitro. Irradiation-induced cell cycle kinetic effects were examined by the calculation of the cell number doubling time (TD), the duration of the cell cycle phases by the BrdU/DNA assay and the number of micronuclei. The number of cells arrested in G2/M and the duration of the delay are dose-related. The effect of irradiation on the duration of cell cycle phases was estimated by following the BrdU-labeled cells through the cell cycle. With increasing radiation doses the duration of the G2/M-phase increases whereas G1- and S-phase show only slight variations. Due to the problems involved in evaluation of radiation effects on the cell cycle a comparison with other methods proves the BrdU/DNA-assay to be a valuable instrument in those experiments. The micronucleus frequency is dependent on irradiation dose. However, after 7.52 Gy the number of micronuclei increases, whereas no cells in G1-phase and no increase of cell number could be detected, indicating a mechanism of micronucleus formation that is not linked with mitosis. PMID- 8465255 TI - Health data on older Americans: United States, 1992. Introduction. Background. PMID- 8465256 TI - Health data on older Americans: United States, 1992. Acute care. PMID- 8465257 TI - Selected issues in long-term care: profile of cognitive disability of nursing home residents and the use of informal and formal care by elderly in the community. AB - In summary, this section suggests that hospital care and physician office care are frequently used community health care services. There were relatively few differences by sex, age, or race in patterns of community health service use. There were differences by sex, age, race, and level of ADL disability in the number of informal helpers a frail elder used. Marital patterns appear to be an important underlying influence on the number of informal helpers. When a spouse is present, he or she becomes the primary and only helper in many instances. The number of informal helpers that a frail elder had was associated with an increased risk of mortality and institutionalization. Overall, there is somewhat more stability than change in the number of informal helpers over the 2-year period. This section, however, could not identify if the composition of the informal helper network remained the same over time. PMID- 8465258 TI - Health data on older Americans: United States, 1992. Patterns of drug prescribing. PMID- 8465259 TI - Health data on older Americans: United States, 1992. Cost of health care and sources of payment. PMID- 8465260 TI - Health of older black Americans. PMID- 8465261 TI - Health data on older Americans: United States, 1992. Functional status and living arrangements. PMID- 8465262 TI - Musculoskeletal disorders: time trends, comorbid conditions, self-assessed health status, and associated activity limitations. AB - In this report, cases of musculoskeletal disease were identified by a yes response to questions involving joint pain and/or physician-diagnosed arthritis in four national surveys for the following objectives: (a) to assess time trends in case prevalence; (b) to describe respondent health status; (c) to estimate prevalence of joint pain by location; (d) to estimate prevalence of selected comorbid medical conditions; and (e) to estimate among these persons the burden of ADL and IADL disability. These surveys were conducted over a 25-year interval (1960-84). Joint pain is the final common pathway through which a number of these disorders operate and could be expected to identify a subset of persons who have not sought medical consultation. Physician diagnosis of disease is an item that is conceptually a measure of severity. In these samples, there were slightly more persons reporting joint pain than reporting a diagnosis of arthritis in most years. Increases in the prevalence of both joint pain and physician-diagnosed arthritis were noted across survey years and for the cohort aged 65-69 years in NHANES I. Although this analysis is based on national data from persons with arthritis, estimates of disability prevalence from national surveys of the total U.S. population (18,28) are also available for comparison. In this report, persons with arthritis suffer from poorer health status and more disability when compared with U.S. population prevalence. Overall, 14 percent of persons aged 65 74 years reported difficulty walking, and 20 percent of persons with arthritis reported this difficulty. In the U.S. cohort aged 75-84 years, 23 percent reported difficulty walking, compared with 31 percent of those with arthritis. Among persons aged 85 years and over, 40 percent reported difficulty walking, compared with 46 percent of respondents with arthritis. It should be recognized that persons with arthritis are included in the total population estimates and these differences in disability prevalence, therefore, could be much larger. It is important to note, however, that for tasks such as toileting, dressing, and managing money, estimates of disability for the total U.S. and arthritic U.S. populations are similar. These data suggest that arthritis may be a large contributor to certain types of disability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8465264 TI - Health data on older Americans: United States, 1992. Technical notes on methods. PMID- 8465263 TI - International aging. PMID- 8465265 TI - Health data on older Americans: United States, 1992. Changes in functional status and risk of institutionalization and death. PMID- 8465266 TI - Health data on older Americans: United States, 1992. Mortality. PMID- 8465267 TI - Health data on older Americans: United States, 1992. Measures of health. PMID- 8465268 TI - A player of many parts: the spotlight falls on thrombin's structure. AB - The wealth of structural information now available for thrombin, its precursors, its substrates, and its inhibitors allows a rationalization of its many roles. alpha-thrombin is a rather rigid molecule, binding to its target molecules with little conformational change. Comparison of alpha-thrombin with related trypsin like serine proteinases reveals an unusually deep and narrow active site cleft, formed by loop insertions characteristic of thrombin. This canyon structure is one of the prime causes for the narrow specificity of thrombin. The observed modularity of thrombin allows a diversity in this specificity; its "mix-and match" nature is exemplified by its interactions with macromolecules (Fig. 20). The apposition of the active site to a hydrophobic pocket (the apolar binding site) on one side and a basic patch (the fibrinogen recognition exosite) on the other allows for a fine tuning of enzymatic activity, as seen for fibrinogen. Thrombin receptor appears to use the same sites, but in a different way. Protein C seems only able to interact with thrombin if the recognition exosite is occupied by thrombomodulin. These two sites are also optimally used by hirudin, allowing the very tight binding observed; thrombin inhibition is effected by blocking access to the active site. On the other hand, antithrombin III makes little use of the recognition exosite; instead, its interactions are tightened with the help of heparin, which binds to a second basic site (the heparin binding site). Thrombin's modularity is a result of the conjunction of amino acid residues of like properties, such as charge or hydrophobicity. The charge distribution plays a role, not only in the binding of oppositely charged moieties of interacting molecules, but also in selection and preorientation of them. Nonproteolytic cellular properties are attributed to 1) the rigid insertion loop at Tyr60A, and 2) a partially inaccessible RGD sequence. The former can interact with cells in the native form; the latter would appear to be presented only in an (at least partially) unfolded state. The membrane binding properties of prothrombin can be understood from the ordered arrangement of calcium ions on binding to the Gla domain. Kringle F2 binds to thrombin at the heparin binding site through charge complementarity; a conformational change appears to occur on binding. The observed rigidity of the thrombin molecule in its complexes makes thrombin ideal for structure based drug design. Thrombin can be inhibited either at the active site or at the fibrinogen recognition exosite, or both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8465269 TI - Free radical scavenging mechanisms during pulmonary thromboembolism in rats. AB - In the present investigation alterations in the free radical generating and scavenging enzymes in platelets, neutrophils (PMNLs), heart and lung homogenates following rat pulmonary thromboembolism have been studied. Thrombosis was induced by intravenous infusion of collagen and adrenaline. Levels of malonaldehyde (MDA) were elevated in the PMNLs after thrombosis. Activities of superoxide dismutase (SOD) and catalase (CAT) were found to increase in platelets and PMNLs respectively. However, there was no significant alteration in the lactate dehydrogenase (LDH), lysozyme (LYS), ratio of xanthine oxidase to dehydrogenase (XO/XH) and PMNLs O2- generation before and after thrombosis. Migration of PMNLs following thrombosis was indicated by increased activity of myeloperoxidase (MPO) in the heart. In addition, pretreatment with allopurinol, a xanthine oxidase inhibitor and indomethacin, a cyclooxygenase inhibitor offered protection against thromboembolism induced death/paralysis. Results suggest the involvement of free radicals in thrombosis. PMID- 8465271 TI - D-dimer plasma concentration in various clinical conditions: implication for the use of this test in the diagnostic approach of venous thromboembolism. AB - Plasma measurement of D-Dimer (DD) represents a definite aid in the diagnostic approach of outpatients with suspected venous thromboembolism (VTE). However, the high sensitivity (about 95%) of the test which allows to rule out VTE when concentrations are below a given cutoff (500 micrograms/L as measured by the ELISA technique) is counterbalanced by a poor specificity (about 40%). Because the specificity might even be lower in patients who are hospitalized we determined the DD plasma concentration in 255 patients who were consecutively admitted in general internal medicine wards with various pathological conditions. The proportion of patients who had DD levels below the cutoff of 500 micrograms/L was 6% (1/18) in patients with VTE and 22% (52/237) in hospitalized patients without VTE: the figure was 21% in patients with pulmonary infections, 14% in patients with other infections, 11% in patients with neoplastic diseases, 34% in patients with coronary or cerebrovascular disease, 19% in patients with cardiac failure, 69% in patients with rheumatologic disease and in 16% in subjects with miscellaneous clinical conditions. The high rate of elevated plasma DD in hospitalized patients questions the usefulness of this test in the diagnostic approach of VTE in aged patients who present with concomitant disease like infections, neoplasia, cardiac failure and many other pathological conditions, except rheumatologic affections and coronary or cerebrovascular diseases. PMID- 8465270 TI - The role of protein kinase C in the initial events of platelet activation by thrombin assessed with a selective inhibitor. AB - The role of protein kinase C (PKC) in platelet activation by thrombin was assessed using a PKC inhibitor Ro 31-7549/001 (R2) which, in vitro, shows more selectivity for PKC than other kinase inhibitors. During early (1.5 s) thrombin induced platelet activation, when phosphorylation of 47 kDa protein (pleckstrin) and myosin light chain by PKC and myosin light chain kinase, respectively, are most readily differentiated, R2 suppressed phosphorylation of pleckstrin more effectively than myosin light chain. R2-inhibited dense granule secretion (measured 0-10 s using quenched-flow techniques) with a dose dependency similar to that for inhibition of pleckstrin phosphorylation, supporting a role for PKC in this process. R2, at 0.5 microM inhibited 47 kDa protein phosphorylation by more than 60%, but had only minimal effects on the kinetics (0-3s) of ADP-induced primary aggregation. At this same concentration, R2 potentiated the thrombin induced rise in cytosolic calcium during early (0-15 s) activation as measured in the presence or absence of external calcium. These data support the hypothesis that activation of PKC during early platelet function helps regulate cytosolic calcium levels by limiting calcium release into the cytosol. PMID- 8465272 TI - Cytosolic free magnesium concentration in human platelets. AB - Although the magnesium ion (Mg2+) is considered to play an important role in cell activation, information is limited by the lack of suitable methods for measuring cytosolic free Mg2+ concentration ([Mg2+]i). We measured [Mg2+]i in resting and activated human platelets using a new fluorescent Mg(2+)-indicator, mag-fura-2. [Mg2+]i was 0.54 +/- 0.14 mM in resting platelets from 15 healthy volunteers. [Mg2+]i was elevated to 1.33 +/- 0.44 mM and 0.92 +/- 0.37 mM in platelets stimulated with thrombin and collagen, respectively. Increased Mg2+ was considered to be derived chiefly from intracellular Mg2+ mobilization. These results suggest that platelet activation is associated with the increase in [Mg2+]i. The estimation of [Mg2+]i using this method is useful for the investigation of mechanism for various cell activation. PMID- 8465273 TI - Stimulation of endothelin production in cultured human endothelial cells by fluorescent compounds associated with blackfoot disease. AB - The fluorescent compounds (FC) in humic substances isolated from the drinking water of endemic areas of blackfoot disease have been characterized as the causative factor of the disease. In this report we studied the effects of these fluorescent compounds on the synthesis and secretion of endothelin-1 by cultured human umbilical cord vein endothelial cells (HUVEC) in order to explore the possible pathological mechanism(s) of FC in the development of atherothrombotic vasculopathy in blackfoot disease. Incubation of confluent HUVEC with FC (100 micrograms/ml) enhanced endothelin mRNA expression. A sensitive ELISA method was developed to quantitate secreted endothelin antigen levels in conditioned medium. Incubation of confluent HUVEC cultures with different concentrations of FC (0-200 micrograms/ml) resulted in concentration-dependent enhanced production of endothelin. No significant changes in endothelin production were observed when subconfluent HUVEC cultures were incubated with FC. FC dose-dependently reduced the growth rate of subconfluent cultured HUVEC and exerted cytotoxic effects on the viability and integrity of confluent HUVEC monolayers. Since endothelin is one of the most potent vasoconstrictors affecting blood pressure and blood flow, and is mitogenic for smooth muscle cell proliferation, these results imply that the enhanced endothelin production and the reduced cell viability and growth rate induced by FC may contribute to the atherothrombotic vasculopathy observed in blackfoot disease. PMID- 8465274 TI - Thrombin generation after physical exercise. AB - Many investigators have studied the influence of physical exercise on hemostatic system and it is well accepted that exercise causes an activation of coagulation as indicated by a shortening of aPTT and by an increase in plasma factor VIII activity and levels. A controversial point remains whether this clotting activation leads to a significant thrombin generation and fibrin formation. The type of physical exercise performed and the methods used to study blood coagulation may be two major sources of discrepancies in different studies. In the last years sensitive and reliable methods became available to evaluate prothrombin activation and thrombin generation. Thus in this study we have investigated the influence of a well standardized treadmill stress test, controlled by the measurement of cardiorespiratory and metabolic parameters, on plasma concentration of different markers of clotting activation in healthy untrained young subjects. Blood samples were also withdrawn just before anaerobic threshold to investigate a possible role of metabolic acidosis in changes of clotting system. PMID- 8465275 TI - Alteration of pharmacokinetics and pharmacodynamics of recombinant hirudin (rHV2 Lys 47) after repeated intravenous administration in dogs. AB - Native hirudin is a heterogenous polypeptide obtained from the medicinal leech, Hirudo medicinalis. Recent advances in molecular biological techniques have led to the availability of large amounts of hirudin in the recombinant form. Recombinant hirudins (rH) are currently being investigated for potential use in the prophylaxis and treatment of deep venous thrombosis (DVT), in disseminated intravascular coagulation (DIC) and during cardiovascular bypass surgery. In this study, one specific variant of rH with a lysine residue in position 47 (rHV2-Lys 47) was administered in dogs in a multiple dose regimen of 2 mg/kg (i.v. bolus) for three weeks with a dosing interval of one week. After each dose, blood samples were collected at regular time intervals, plasma separated and stored at 4 degrees C. Concentrations of rHV2-Lys 47 in each sample were determined using an enzyme-linked immunosorbent assay (ELISA). Ex vivo antithrombin responses measured included activated partial thromboplastin time (APTT), calcium-thrombin time (Ca++TT-10 NIH units/ml) and a chromogenic anti-IIa assay. It was the purpose of this study to detect any sensitization or desensitization of antithrombin responses when rHV2-Lys 47 is used in a repeated fashion such as would be expected in the prophylaxis of DVT. The results indicated that there was no attenuation in the responses; however, there was a sensitization of response as measured by the Ca++TT (10 NIH units/ml). These findings could have major implications in the clinical use of rH where this drug is expected to be used in a multiple dose regimen. PMID- 8465276 TI - In vivo pharmacology of aprosulate, a new synthetic polyanion with anticoagulant activity. AB - The in vivo effects of a new synthetic inhibitor of blood coagulation, aprosulate sodium, were investigated. Intravenous bolus injection of aprosulate or standard heparin in rats produced an immediate prolongation of the APTT which were characterized by a moderate dose-dependency and long-lasting duration when compared with those of standard heparin. Standard heparin inhibited plasma factor Xa activity, but aprosulate did not even at the highest dose used. Both agents inhibited thrombus formation in a dose-dependent manner in an arterio-venous shunt model. At antithrombotic doses, standard heparin prolonged the bleeding time measured by the tail transection method, but aprosulate did not. The present results suggest that aprosulate has promising in vivo profile as an anticoagulant and antithrombotic agent. PMID- 8465277 TI - Fibrinolytic response to venous occlusion in healthy subjects: relationship to age, gender, body weight, blood lipids and insulin. AB - The physiological variability of fibrinolytic response to 20 min upper arm venous occlusion was studied in 191 healthy women and men, 19-80 years old. It was observed that fibrinolytic response measured by the absolute amount of t-PA antigen after venous occlusion increased with increasing age (from 10.7 at 19-30 years to 25.0 ng/ml at 71-80 years), was higher in men than in women (20.9 vs 15.6 ng/ml), higher in obese than in slim subjects (29.5 vs 12.3 ng/ml) and higher in subjects with moderately elevated blood cholesterol (33.3 vs 18.2 ng/ml) and triglycerides (30.0 vs 24.4 ng/ml, all p < 0.05 or less) than in subjects with normal levels of these variables. Due to simultaneous increase in basal levels of t-PA antigen in all these cases, relative increases in t-PA antigen after venous occlusion were not altered. Fibrinolytic response measured by t-PA activity, but not with euglobulin clot lysis time, increased with age. PAI-1 antigen was not affected by venous occlusion, while PAI activity decreased to zero in most subjects (in 61-80%) regardless of age, gender or blood lipids. However, in obese subjects and especially in subjects with elevated insulin, fibrinolytic response was reduced as determined by residual PAI activity after venous occlusion (1.3 and 10.6 IU/ml, respectively) due to the increased basal level of PAI-1. It was concluded that age, gender, body weight, blood lipids and insulin significantly modulate fibrinolytic response to venous occlusion. PMID- 8465278 TI - The antithrombotic effect of low molecular weight synthetic thrombin inhibitors, argatroban and PPACK, on He-Ne laser-induced thrombosis in rat mesenteric microvessels. AB - The antithrombotic effect of low molecular weight synthetic thrombin inhibitors, argatroban ((2R, 4R)-4-methyl-1-[N2-[(3-methyl-1, 2, 3, 4-tetrahydro-8 quinolinesulfonyl)-L-arginyl]-2-piperidinecarbox ylic acid monohydrate]) and PPACK (D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone) on He-Ne laser induced thrombosis in rat mesenteric microvessels was studied. Both inhibitors showed a significant antithrombotic effect at 0.5 mg/kg which lasted for 50 min and 50-60 min using argatroban and PPACK, respectively. A dose-dependent effect was observed in arterioles and venules. The results suggest that thrombin plays an important role in the formation of a platelet thrombus in vivo. PMID- 8465279 TI - [Development of sports medicine]. PMID- 8465280 TI - [Rehabilitation after head injuries--local use of regional knowledge]. PMID- 8465281 TI - [Preoperative fasting--softening of rigid rules?]. PMID- 8465282 TI - [High-dose glucocorticoids in surgery and trauma]. PMID- 8465283 TI - [Anti-inflammatory agents in acute tissue trauma. Choice and effects]. AB - The choice of drugs to reduce pain and excessive inflammatory reactions after surgery or accidental trauma is reviewed and discussed, with particular reference to a series of Norwegian studies based on bilateral oral surgery. In this model, paracetamol has proved capable of reducing post-operative swelling by about 30%, while acetylsalicylic acid (in common analgesic doses) failed to reduce or even tended to increase swelling. Paracetamol is a recommendable alternative for reducing acute post-traumatic pain and swelling, while acetylsalicylic acid should be avoided. Non-steroidal anti-inflammatory drugs which efficiently reduce rheumatoid swelling may provide good pain relief, but the effect on an acute post operative swelling is less impressive. In the oral surgical model, glucocorticoids reduced post-traumatic swelling by about 50% and provided better or at least as good pain relief as any tested non-steroidal anti-inflammatory drug, including paracetamol. Single dose or short-term administration of a glucocorticoid is recommended as an efficient and valuable means of reducing both pain and excessive inflammation in surgery and traumatology. Of practical implication in traumatology is the finding that, for both paracetamol and glucocorticoids, almost the same reductions were recorded in swelling and pain whether the drug was administered prior to surgery or 2-3 hours afterwards. PMID- 8465284 TI - [Response to inhaled bronchodilators in chronic airway obstruction]. AB - OBJECTIVE: To assess the proportion of patients with chronic limited airflow who obtain a meaningful bronchodilatory effect from the betaadrenergic agonist salbutamol and the anticholinergic agent ipratropiumbromide. PATIENTS: 198 patients with varying degrees of airflow limitation. The state of all patients was stable. METHODS: Spirometry was recorded before inhalation, and ten, 20 and 30 minutes after inhalation of 0.2 mg salbutamol or 0.04 mg ipratropiumbromide. RESULTS: FVC increased by 0.5 litres or more in 77 patients with salbutamol and in 104 patients with ipratropiumbromide. FEV1 increased by 0.3 litres or more in 76 patients with salbutamol and in 95 patients with ipratropiumbromide. In 77 patients, neither of the drugs caused this improvement in FEV1. CONCLUSION: In patients with chronic limitation of airflow use of inhaled bronchodilators should be based on the proven clinically significant effect of the drug in question. PMID- 8465285 TI - [Diagnostic imaging in sciatica. A short historical overview and current status]. AB - Cotugno described the clinical entity of sciatica in 1764. However, the association between sciatica and compression of lumbar nerve roots was not realized until the 1920s. Back surgery for herniated nucleus pulposus then became fashionable, and plain radiography and myelography enabled preoperative mapping. Recently other imaging techniques have emerged, such as computed tomography and magnetic resonance imaging. This has increased the knowledge of the etiology of lumbar root compressions, and invasive therapies for sciatica have become more diversified. It is easy to lose perspective among the available imaging procedures and therapeutic techniques. The aim of this paper is to present the current status from a historical point of view, with special emphasis on the most common imaging methods for the investigation of lumbosacral radiculopathies. PMID- 8465287 TI - [Gastrointestinal manifestations in neurofibromatosis]. AB - Gastrointestinal involvement in neurofibromatosis occurs in three major forms: solitary neurogenic tumours, diffuse ganglioneuromatosis and visceral vasculopathy. The entire gastrointestinal tract may be affected. According to the literature, 10-25% of the patients with neurofibromatosis develop intestinal manifestations. However, the recorded incidence is probably too low, since many cases are undiagnosed. Two cases of large plexiform neurofibromas and diffuse ganglioneuromatosis of appendix and intestine are reported. PMID- 8465286 TI - [Accessory soleus muscle as a tumor in the ankle region]. AB - We report the case of a 21-year ice hockey player with an accessory soleus muscle located medially in the ankle region. The swelling made it increasingly difficult for him to fit his skating boots and caused some pain during play. He was successfully treated by excising the muscle. Previously, the diagnosis was verified surgically in most reported cases. Like most recent authors, we believe that the diagnosis can be confirmed by CT-scan and/or MRI-scan. Surgical excision of the muscle should be reserved for symptomatic cases. PMID- 8465288 TI - [Non-typhoid Salmonella aortitis]. AB - Non-typhoid Salmonella enteritis may be complicated by aortitis. Three cases of Salmonella enteritidis aortitis are described. One patient, who survived, was operated with resection of the infected part of the aorta. An axillo-femoral bypass was made. The patient was treated for 18 months with antibiotics. The two patients who died were only treated with antibiotics. Aortitis is diagnosed by means of blood-cultures and topographic examination of the aorta with CT scanning, ultrasonography or angiography. The treatment of Salmonella aortitis is a combination of surgery and long-term administration of antibiotics. PMID- 8465289 TI - [Sports medicine in Norway]. AB - In Norway sports medicine is not organized as a single specialty among the medical disciplines. It involves work carried out by doctors with different specialties, dominated by physical medicine and rehabilitation, along with orthopaedic surgery, internal medicine, gynaecology and physiology. Preventive work, acute treatment and rehabilitation of injured athletes, as well as scientific work in the field of sports and sports medicine, are major elements of this field of medicine. It is important to educate medical students and doctors in sports medicine. This education started years ago at the university hospitals in Oslo and Trondheim. It is expected to be extended, and to become organized in future as an integrated part of the regular education of medical students and the post-graduate education of doctors. PMID- 8465290 TI - [The importance of physical activity in the modern health concept]. AB - Physical activity has increasingly become an integrated part of both the prevention and treatment of many diseases. This approach is based on data from large studies linking either physical activity or physical capacity to the incidence of disease. Furthermore, regular physical activity can influence health indirectly, since people who become physically active also tend to change other health-related habits in a positive direction. The author outlines some specific effects of exercise on certain diseases, and discusses the data indicating how much training is necessary to obtain the desired effects on health. PMID- 8465291 TI - [Optimal use of acid-inhibitors in acid-related diseases. Physiological and physiopathological considerations with implications on therapeutic choice]. AB - Most animal species produce gastric acid. This acid denaturates the proteins in the food and thus makes them accessible to the proteolytic enzymes. The main function of the gastric acid is probably to kill swallowed microorganisms. However, the gastric acid plays an essential role in the pathogenesis of common and important diseases like peptic ulcer and reflux oesophagitis. Drugs that inhibit the secretion of gastric acid suppress both symptoms as well as lesions in patients with peptic ulcer or reflux oesophagitis. However, both reflux oesophagitis and peptic ulcer tend to recur when the acid-inhibitory treatment is stopped. In this overview the author warns against long-term profound inhibition of acid, since, in the long term, both the reduced killing of microorganisms as well as the secondary hypergastrinemia may induce increased risk of gastric cancer. In this context the role of the enterochromaffin-like (ECL) cell in gastric carcinogenesis is thoroughly discussed. There is probably a spectrum of neuroendocrine tumours in the stomach as like in the lungs, which also are foregut derived. Gastrin regulates the function (release of histamine) as well as the growth of the ECL cell, and a maximal trophic effect seems to be reached at a lower gastrin concentration than previously realized. PMID- 8465292 TI - [Postoperative enteral nutrition]. AB - The need for postoperative nutrition is often discussed, but no consensus has been reached regarding the assessment of this need. The common opinion is that patients who are unable to feed themselves by 5-7 days after the operation need nutritional support. This is commonly given parenterally via a central venous catheter. This method may lead to sepsis. Owing to the serious complications, alternatives have been searched for. Methods for enteral ways of support and suitable preparations have been evaluated. We have tried one of these methods together with one of the many preparations. Peptison has been administered continuously through a peroperatively placed jejunal catheter. This technique and its possible advantages are described. By this method patients can be given sufficient nutritional support with no or only few complications. We consider this method to be a good alternative to parenteral infusion. PMID- 8465293 TI - [Prevention of aspiration--preoperative fasting. Time for reevaluation of old routines?]. AB - The article reviews the epidemiology, pathophysiology and recent clinical research on aspiration prophylaxis and preoperative fasting before surgical procedures. Elective, pain-free patients should be allowed a glass of clear fluid up to two hours before start of anaesthesia. A light meal should be allowed up to four hours before the procedure. The anaesthesist should always make an individual evaluation of patients with pain or gastrointestinal obstruction, or who have received opioids. Aspiration of gastric contents and/or prophylactic use of histamine H2 antagonist or sodium citrate may be considered. The use of prophylactic treatment should always be evaluated against the side-effects of such treatment and the very low occurrence of serious sequelae from aspiration of gastric contents into the lungs. PMID- 8465294 TI - [Who is responsible for EDP-based records? Experiences with introduction of EDP in a public health center]. AB - In 1991, about 150 general practitioners in 37 health care units in the county of Oslo introduced computerized systems of case records which replaced the previous paper records. The hardware units were located outside the units, and were physically interconnected by a large computer network within the county of Oslo. By losing physical contact, the general practitioners also lost control of their patient records. The files could be looked into and manipulated with or without the doctors' knowledge. It was no longer clear who was responsible for the computerized case records. These experiences are discussed, paying attention to the Norwegian legislation and official regulations in the area. The conclusions are that a health care unit using EDP should have its hardware at the unit itself. The chief doctor of the unit should be responsible for the daily management of the EDP-unit, and for safeguarding the confidentiality of the patient records. PMID- 8465296 TI - [The lobotomy debate in Norway]. PMID- 8465295 TI - [The lobotomy debate in Norway]. PMID- 8465297 TI - [Records, subjectivity and dissatisfied patients]. PMID- 8465298 TI - [Regional psychiatric function for especially difficult and dangerous mentally disturbed persons]. PMID- 8465299 TI - [The concept of disease in the light of economic and political realities]. PMID- 8465300 TI - [Effects of vitamins and trace elements on immune defence]. PMID- 8465301 TI - [Medical education--ready for failure?]. PMID- 8465302 TI - [Empathy]. PMID- 8465303 TI - [Ethical mobilization in preventive health care]. PMID- 8465304 TI - [Chronic hepatitis C infection. Some aspects brought up again through patients' complaints]. PMID- 8465305 TI - [Life style]. PMID- 8465306 TI - [Diphtheria in Batsfjord. "Old" diseases may return]. PMID- 8465307 TI - [When the media take over]. PMID- 8465308 TI - [Multiple organ failure. "Horror autotoxicus?"]. PMID- 8465309 TI - [Spinal injuries]. PMID- 8465310 TI - [Intravenous anesthetics]. PMID- 8465311 TI - [Thoracolumbar injuries. Surgical treatment of patients with neurological damage]. AB - This article presents the neurological outcome after surgery of a series of 54 patients with damage to the spinal cord and/or cauda equina caused by thoracolumbar injuries. The fractures, dislocations or fracture-dislocations were all reduced and stabilized by a Harrington distraction device or transpedicular fixation system (posterior segment fixator). Peroperative inspection revealed that correction and distraction alone may be inadequate to achieve intraspinal decompression. Additional anterior decompression by posterolateral approach was necessary in 31 patients (57%). In this series there was an unexpected high rate of dural rents. Tears were found in 11 patients (20%) and nerve roots (cauda equina) appeared to have herniated through the tear in eight. Significant improvement of the neurological deficits was obtained in 81%. The improvement rate was much better in patients with incomplete lesions than among those with complete lesions. We are convinced that surgery improves the neurological outcome if carried out at the proper time, after sufficient decompression of the spinal cord and nerve roots, and repair of dural rents. PMID- 8465312 TI - [Pathogenetic mechanisms in acute respiratory failure in adults]. AB - A large variety of mediators and mediator systems are involved in the pathogenesis of acute respiratory failure in adults, and the complexity of the syndrome should be considered in both prophylaxis and therapy. The locally accentuated and organ-related activation of several mediator systems over a long period of time is likely to be responsible for the irreversible damage to cells and tissue. Surfactant dysfunction or degradation, regardless of the cause, contributes to the pathophysiology of severe respiratory failure, and might be a common denominator in the pathogenesis of the syndrome. Cytokines from macrophages are important, since these mediators have the potential to convert a primarily functional and reversible systemic reaction into irreversible damage to specific organs. PMID- 8465313 TI - [Meningoencephalitis after Mycoplasma pneumoniae infection]. AB - A 15 year-old boy developed meningoencephalitis two weeks after onset of a respiratory tract infection caused by Mycoplasma pneumoniae. Central nervous complications are seen in 2-7% of patients hospitalized for M pneumoniae infection. Meningoencephalitis, meningitis, ataxia, polyradiculitis, psychosis and a few cases of apoplexy have been reported. In clinical practice one should be aware of M pneumoniae in the differential diagnosis of patients with suspected microbiologically induced central nervous complications. The pathogenetic aspects and prognosis are briefly discussed. PMID- 8465314 TI - [Tracheal compression treated with endoluminal stents]. AB - Tracheobronchial stenoses can be caused by growth of endoluminal tumour or by external compression. Endoluminal tumours can be treated by means of endoscopically applied lasers, while tumours in the oesophagus, thyroid gland, or lymph nodes which compress the airways connor be reached by this type of treatment. We report four cases where life-threatening compression of airways by malignant tumours was successfully relieved by stenting the trachea with a silicone stent, Endoxane. The stent was inserted through a rigid bronchoscope, and the operative procedure was uneventful in all cases. Postoperatively, the patients did not experience severe discomfort from the stent, and neither dislocation of the stent nor retention of secretions was a problem. All the patients died of cancer-related causes, but none died from suffocation. It is concluded that tracheo-bronchial stenting is a valuable supplement to irradiation in palliative treatment of airway compression of airways caused by malignant tumours. PMID- 8465315 TI - [Bacterial arthritis]. AB - During the years 1980-89, 13 patients were hospitalized because of bacterial arthritis of the peripheral joints. There were five juvenile patients (under 15 years of age). The remaining eight patients were adults, of whom seven were older than 50 years. The mean delay in establishing the diagnosis was four days (0-10 days). Monarthritis was found in 12 patients, and in one patient two joints were involved. The most commonly affected joints were the shoulder (four cases), knee (four cases), ankle (three cases), hip (two cases) and toe (one case). A predisposing condition was found in five patients, and three cases suffered from reduced mobility of the joint at follow-up. Staphylococcus aureus was the most common etiologic agent. PMID- 8465316 TI - [Malacoplakia in the endometrium. A rare cause of postmenopausal bleeding]. AB - Malacoplakia of the endometrium and the rest of the female genital tract is rare. The condition is usually postmenopausal, and an important clinical finding is vaginal bleeding. Clinically, what is actually malacoplakia is often suspected to be a malignant disease. Pathologically, however, malacoplakia is easily distinguishable from carcinoma, owing to the typical, light colour of the swear when examined under the microscope, showing. Histiocytes with abundant eosinophilic granular cytoplasm and varying degrees of intracellular and extracellular Michaelis-Gutman bodies. As far as we know, we describe the first case in Norway of postmenopausal bleeding in a 78 year old woman, caused by malacoplakia of the endometrium. PMID- 8465317 TI - [Testing aerobic energy metabolism]. AB - The purpose of testing the aerobic metabolism is to evaluate the athlete's capacity for aerobic ATP synthesis during the events she/he is preparing for. In endurance events lasting less then eight minutes the maximal O2-intake is the most important determinant of performance, with an increasing contribution of anaerobic metabolism as intensity is raised. In long distance events (> 8 min), the capability to avoid lactate production is more important. Although a high maximal O2-intake will reduce lactate production at a given intensity, other factors are also involved, probably confined to the working muscles. Finally, in all endurance events, another important factor is working economy. Direct measurements of maximal O2-intake, and of O2-intake and lactate concentrations in blood at several submaximal intensities, constitute a test complex that is capable of separating these abilities. PMID- 8465318 TI - [Anaerobic capacity--theoretical basis and methods for practical testing]. AB - The ATP turnover rate is raised during highly intensive exercise. Part of the ATP used is regenerated anaerobically independently of oxygen consumption. Lactate production accounts for 75% of the anaerobic ATP production, while breakdown of phosphocreatine accounts for the remaining 25%. Anaerobic processes can provide energy for about one minute's exercise during exhausting exercise lasting several minutes. An athlete may improve his anaerobic capacity by 10% during two months of proper training, and the measured improvement is of significance for athletes. The accumulated oxygen deficit has been introduced to quantify the anaerobic release of energy during exercise. The method is discussed briefly. PMID- 8465319 TI - [Integrins, structure and function]. AB - Integrins are molecules of central importance in physiological and pathological processes. Integrins are an important factor in intercellular adhesion processes and cell migration leading to normal architecture of tissue, in inflammatory and tumour cell migration and in reparatory processes of damaged tissue. The integrin designation is derived from the role of these substances in integrating processes within and outside the cell. Therefore these membrane proteins play a role in cell growth, differentiation and gene expression. The role played by integrins in cell signal transduction and inflammation is discussed in this article. During the past few years we have seen an explosion of research in this field, which may lead to therapeutic benefits in a few years time. PMID- 8465320 TI - [Diagnostic tests--use and interpretation]. AB - Diagnostic tests are often difficult to interpret. Use of methods intended for binary tests leads to loss of information when these methods are applied to quantitative tests. The author reviews methods for correctly interpreting qualitative and quantitative tests, for finding the best combination of tests, and for assessing when to test. PMID- 8465321 TI - [Is left ventricular hypertrophy in hypertension a marker for coronary risk factors?]. AB - 86 asymptomatic men with mild to moderate hypertension were examined by echocardiography, exercise ECG and measurements of their lipid profile. Left ventricular hypertrophy, defined as an increased left ventricular mass index > or = 130 g/m2, was found in 38 (44%) patients. Only two men showed evidence of silent ischemia during maximum exercise. The men with left ventricular hypertrophy had a higher systolic blood pressure at rest (p = 0.0002), at submaximal (p = 0.02) and maximal exercise (p = 0.01). The prevalence of smokers was the same, as were the concentrations of lipids, lipoproteins and apoproteins in the two groups. Except for a higher blood pressure, left ventricular hypertrophy is not a special marker for other coronary risk factors. PMID- 8465322 TI - [Primary health care and patients with severe mental disorders living at their own homes]. AB - Lack of relevant information has been stated as a major obstacle to the development of better services for persons with serious mental disorders. The information on patients not in contact with the specialist services seems to be particularly incomplete. The objective of this study was to describe a subgroup of psychiatric patients living in a semi-rural municipality in Norway who had no contact with the specialist mental health services. 15 patients below 70 years of age (0.3% of the population at risk) with a diagnosis of schizophrenia from psychiatric hospital, and still on neuroleptic maintenance-treatment prescribed by a primary physician were identified. The authors present the characteristics of this group, with emphasis on their health status, their social network, and the actual treatment and care provided, and discuss the need for clear case definitions in community surveys of psychiatric disorders. They finally describe the current trend towards new and improved models for cooperation between the primary health care and the specialist services. PMID- 8465323 TI - [Combination therapy with antidepressive agents--risks for interactions]. PMID- 8465324 TI - [The minister of health and the tobacco policy]. PMID- 8465325 TI - [Does the crisis of health services originate in shortage of resources or shortage of theories?]. PMID- 8465326 TI - [Child and adolescent psychiatry--will it be part of Norwegian health care in the year 2000?]. PMID- 8465327 TI - [Drinking water and occurrence of colorectal polyps. An epidemiological study in Telemark]. PMID- 8465328 TI - [Income differences between female and male physicians]. PMID- 8465329 TI - [Anti-shock trousers--over and out? From fighters and Vietnam to civilians]. PMID- 8465330 TI - [Sinusitis--research in general practice]. PMID- 8465332 TI - [Sinusitis in general practice--a diagnostic challenge]. AB - Sinusitis is a common problem in general practice, but diagnosis is often difficult. The greatest clinical challenge is to distinguish between purulent and nonpurulent sinusitis. This differential diagnosis has consequences for treatment. A questionnaire was sent to a randomized sample of Norwegian general practitioners and to all ear, nose and throat specialists in private practice. 79% of the general practitioners felt that diagnosis is more uncertain for sinusitis than for otitis media. When anamnestic questions and clinical findings were grouped, it was shown that general practitioners consider pain to be much more relevant in the differential diagnosis than purulent secretion. The ear, nose and throat specialists consider pain and purulent secretion to be equally important in the differential diagnosis. Pain in cheek and forehead, and pain in the upper teeth are regarded as the most relevant single anamnestic symptoms. Duration of illness is considered to have little differential diagnostic relevance. Among supplementary tests only C-reactive protein is regarded as helpful. X-ray and erythrocyte sedimentation rate are evaluated as far less relevant. PMID- 8465331 TI - [Doxazosin (Carduran)--a research survey]. AB - 4,260 patients were included in an open surveillance study simultaneously with the introduction of doxazosin for treatment of essential hypertension in Norway. The main aim of the study was to systematically collect information on side effects and events in patients being treated with a new drug. The effect on blood pressure, heart rate and lipids was also recorded. The study lasted for one year. 21 deaths were reported. 53% of the patients reported side effects and/or events. The frequency of side effects was particularly high during the first month of treatment. No new types of side effects were found. The initial higher frequency of reported side effects referred to all organ systems, and was also of the same magnitude in the different systems. A relation was found between certain cardiac side effects and/or events and cessation of previous medication upon starting treatment with doxazosin. The study shows that certain safety precautions should be observed in patients with coronary heart disease and heart failure. In three patients, doxazosin should be used only in combination with more specific treatment. Special caution should be observed when changing the specific basic treatment. Doxazosin had a very favourable antihypertensive effect. A drop in cholesterol and triglycerides was observed, as expected. The HDL-cholesterol value declined, which was unexpected. The results are difficult to interpret, owing to lack of a control group. On the other hand, the study shows how high blood pressure is being treated with drugs in ordinary practice. The authors discuss the methodology of surveillance studies. PMID- 8465333 TI - [Public opinion on organ donations from recently decreased persons. A questionnaire study]. AB - Organ transplantation is at present hampered by a shortage of organs. This problem is increasing, and can be helped by more information and knowledge among health professionals and the general public. The frequency of families who consent to donation of organs from a recently deceased family member varies from country to country and has previously not been examined in Norway. In this survey a random sample of 1,050 persons (15 years and older) were interviewed. 71% (95% CI 68-74) would consent to donation of an organ from a close family member. PMID- 8465334 TI - [Reticulocytes--new possibilities with automated counting]. AB - A fully automated reticulocyte counter, Sysmex R-1000 has been evaluated at three Norwegian hospitals. The instrument measures fluorescence-labelled RNA in the reticulocytes by flow cytometry. It also generates information on reticulocyte maturity. Instrument precision was superior to that achieved with the routine visual counting method. Samples preserved at room temperature remain stable for one day, whereas samples preserved at 5 degrees C remain stable for four days. An increasing number of reticulocytes is often the first sign of marrow regeneration after bone marrow transplantation or treatment of leukaemia with cytostatica. In patients with chronic renal failure who are receiving erythropoietin, the increase in reticulocytes is seen within days, and precedes the increase in haemoglobin by 2-3 weeks. PMID- 8465335 TI - [Residual urine after intermittent catheterization in patients with spinal cord injuries]. AB - Residual urine following catheterization was studied using ultrasonography (Ultramark II Scientific Medical System) in 12 patients with spinal cord injury, for an average of four months (range 3-7 months) after time of injury. All patients were examined three times. Urinary tract infections were also registered, and the functional type of the urinary bladder was identified by cystometric examination. Ultrasonography showed residual urine volumes after 25 of a total of 36 catheterizations (70%). In seven of these catheterizations the residual urine volume exceeded 50 ml, and in two cases was more than 100 ml. None of the patients had a residual urinary volume of more than 50 ml after all three catheterizations, but in all but two patients, some residual urine volume was found after at least one of the catheterizations. Low and non-significant correlations were found between residual volume and frequency of urinary tract infections. It is possible that even small residual urine volumes after catheterization may predispose for urinary tract infections in these patients. PMID- 8465336 TI - [Urinary bladder fistulas]. AB - During the period 1978 to 1991, 19 patients were treated for fistula of the urinary bladder, 12 of the fistulas were enterovesical, four vesicovaginal, one vesicouterine and two vesicocutaneous. Most of them occurred after diverticulitis or operation, or when the patient suffered from a malignant disease. Four patients received conservative treatment. One patient decided against an operation, two were inoperable, and one fistula closed with use of an indwelling catheter. 15 were operated on. 12 extirpations of fistula were carried out. Additional resection of intestine was performed in seven patients and hysterectomia in two patients. Other procedures included two enterostomias and one ileum bladder. In ten patients postoperative courses were uneventful. Four patients died during the first month after operation. One suffered a relapse, and another damage to the nerves of the bladder. PMID- 8465337 TI - [Overtraining among elite athletes--causes, diagnosis and treatment]. AB - Overtraining is an imbalance between training and recovery. We review the pathogenesis of overtraining, with emphasis on the neuroendocrinal changes which occur in response to acute overtraining. At present, no sensitive and specific tests are available to allow early diagnosis of overtraining. The diagnosis is based on medical history, clinical evaluation and exercise testing. The treatment is rest, and may take weeks to months. PMID- 8465338 TI - [Physical activity and the metabolic syndrome]. AB - Hypertension may be accompanied by decreased insulin sensitivity, lipid abnormalities and increased haemostatic risk, all of which, constitute risk factors for coronary artery disease. Modifications of lifestyle, including more physical exercise, are important, and may reduce the coronary risk profile. Physical activity has been shown to lower blood pressure, reduce hypertriglyceridemia, improve insulin sensitivity and increase the fibrinolytic capacity. Hypertensive patients should be encouraged to increase physical activity as an adjuvans to both pharmacological and non-pharmacological treatment of high blood pressure. PMID- 8465339 TI - [Growth hormone and prolactin receptors belong to a new receptor family. Biological and medical aspects]. AB - The molecular structures of the receptors of growth hormone and prolactin have recently been identified by molecular cloning, and have been characterized in a number of species and different tissues. The receptors consist of one polypeptide chain with a single transmembrane region. The extracellular region contains cysteines for disulphide bonding and potential sites for glycosylations. The intracellular part which mediates the biological actions displays considerable heterogeneity of size. A high degree of homology is demonstrated between the extracellular part of these receptors and the receptors of a number of cytokines, interferons and growth factors. Together they comprise a new family of receptors called the cytokine/growth hormone/prolactinreceptor family. Their structure is reviewed, along with the actions of growth hormone and prolactin in vivo. In spite of numerous biological effects the molecular mechanisms of actions for this class of receptors are unknown, even though they convey important cell regulatory functions. The molecular analysis of growth hormone receptor has provided new medical insight on the results of growth hormone replacement therapy in persons with deficient growth. PMID- 8465340 TI - [Smoking habits among Norwegian soldiers in Lebanon 1986]. AB - The smoking habits in 287 Norwegian soldiers, mean age 24 years, who served for six months in the United Nations' peace-keeping forces in Lebanon was studied by self-administered questionnaire and determination of serum-thiocyanate. According to the questionnaires and verified by serum thiocyanate 42% were non-smokers at departure, 88% of them were still non-smokers at return. 7% of the smokers quit smoking while in Lebanon. The other smokers increased the consumption of cigarettes. The study indicates that campaigns against smoking should preferably be directed toward the youngsters since success among them will have long lasting effect. PMID- 8465341 TI - [Lost faces are restored]. PMID- 8465342 TI - [Blood cultures in emergency situations]. PMID- 8465343 TI - [Behavioral theory and preventive work in practice]. PMID- 8465344 TI - [Breast implants and connective tissue diseases]. PMID- 8465345 TI - [Medical education--ready for failure?]. PMID- 8465346 TI - [An echo of another pain. Physicians' meeting with the hidden violence against women]. PMID- 8465347 TI - [Does higher efficiency adversely affect patient care? Some thoughts on Oslo psychiatry prior to year 2000]. PMID- 8465348 TI - [SLE (systemic lupus erythematosus)-related clinical features in dogs]. AB - Three dogs presented with lameness and/or vague clinical signs. The results of immunological tests were suggestive of a SLE-related syndrome. ANA (antinuclear antibodies) titres were very high, 1:40960 in one of the dogs, and antibodies against single-stranded DNA were detected. Complement levels were very low in two dogs. Antibodies against histones were detected in both the serum and the synovial fluid of one dog. In another dog there was evidence of high concentrations of PCNA antibodies, which in humans are specific for SLE. It is concluded that the three dogs showed signs of a syndrome possibly related to SLE. The description of the clinical signs and of the laboratory diagnostics serve as a clinical demonstration to draw colleagues' attention to this nosologically interesting clinical syndrome and to the need to request specific immunological tests when this syndrome is suspected. PMID- 8465349 TI - [Antibiotic sensitivity of bacteria isolated by health services in The Netherlands]. PMID- 8465350 TI - [An umbilical cord broken off too shortly]. PMID- 8465351 TI - [Umbilical cord broken off too shortly]. PMID- 8465352 TI - [Tuberculosis in cattle]. PMID- 8465353 TI - [Overcharging: keeping both feet on the ground and going a step forward]. AB - The intrinsic value of animals and their place in human society influence veterinary practice. The role-responsibility of the veterinarian is under pressure of practical circumstances, client requests and constraints of breeding and management systems. A reflection on human needs as related to the intrinsic value and welfare of animals, is required inside and outside the profession. It is in the interest of life to think and act out of total ecological concepts. In order to be better prepared to deal with ethical problems in practice, students should receive adequate training. The assumed value-free research and the need for outside financial support are a hindrance for research projects that aim at sustainability of human and animal life. It is concluded that the profession needs a philosophy about her objectives. PMID- 8465354 TI - Health effects in man from long-term exposure to pesticides. A review of the 1975 1991 literature. AB - The scientific literature published over the period 1975-1991 on long-term health effects from prolonged exposure to pesticides has been reviewed, in order to document the state-of-knowledge on the mortality and morbidity of groups of the population exposed to pesticides. Specific aims of the review were to identify (1) which groups of the population have been more broadly surveyed, (2) which adverse effects have been consistently associated with specific pesticide exposures, (3) which are the pesticides of concern and (4) which health effects would require special attention in future research. The literature on acute effects and animal toxicology studies have not been considered at all in this monograph. In the period of interest, 440 papers have been published. Apart from 97 reviews and a small number of case reports, approximately half of the original investigations were of the case-control design (n = 108), while the remaining papers reported results from proportionate mortality (n = 10), cohort (n = 66) or cross-sectional studies (n = 51), carried out on pesticide applicators (n = 48), agricultural workers (n = 26) or people employed in the pesticide manufacturing industry (n = 50). Most of the case-control studies related to cases of cancer from various sites, especially myelolymphoproliferative disorders (MLP) and soft tissue sarcomas (STS). When compared to the general population total mortality has been found to be consistently lower among pesticide manufacturers as well as among other groups of workers. This observation has been mostly attributed to the 'healthy worker effect' or, in the case of agricultural workers, to the healthier lifestyle of farm families. With the exception of deaths by accidental causes, non-cancer causes of death (mainly represented by cardiovascular diseases), were generally found to be less frequent than expected among manufacturers or users of pesticides, in particular among farmers. No consistent evidence of a global cancer mortality different from that of the general population has been reported among pesticide manufacturers or applicators. On the other hand, the papers examined have been strikingly consistent in reporting a low overall cancer risk among agricultural workers; life-style, clean air, low prevalence of smoking have been hypothesized so as to explain this observation. Numerous studies considered the possible link between exposure to phenoxyherbicides and occurrence of certain types of cancer, especially STS and MLP disorders.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8465355 TI - Lobar hemorrhages. Where do they come from? How do they get there? PMID- 8465356 TI - Predictors of major vascular events in patients with a transient ischemic attack or nondisabling stroke. The Dutch TIA Trial Study Group. AB - BACKGROUND AND PURPOSE: Very few studies have addressed the identification of prognostic factors in patients with a transient ischemic attack or minor stroke. METHODS: We prospectively studied the prognostic value of clinical, laboratory, radiological, and electrocardiographic findings in 997 patients with a transient ischemic attack and 2,130 patients with a minor stroke who were entered into a multicenter clinical trial. The mean follow-up period was 2.6 years. RESULTS: A total of 302 patients died (212 from a vascular cause), 272 had a stroke, and 200 had a cardiac event. By means of a multivariate analysis we identified the following independent risk factors for stroke, myocardial infarction, or vascular death: age of > 65 years; male sex; dysarthria; multiple attacks; diabetes; angina pectoris; intermittent claudication; computed tomographic evidence of any cerebral infarct, especially a border zone infarct or white matter hypodensity; and electrocardiographic evidence of an anteroseptal infarct, ST depression, left ventricular hypertrophy, or left atrial conduction delay. Protective predictors were monocular attacks only or the presence of rotatory dizziness. CONCLUSION: A limited number of easily obtainable characteristics are powerful predictors of major vascular events in patients with cerebral ischemia. PMID- 8465357 TI - Prognostic factors in first-ever stroke in the carotid artery territory seen within 6 hours after onset. AB - BACKGROUND AND PURPOSE: We sought to detect prognostic factors related to functional outcome during the first 6 hours after a first-ever stroke in the carotid artery territory. METHODS: All patients with these characteristics seen during a 3-year period were included. Outcome was evaluated according to a modified Rankin scale. The following variables were examined at univariate analysis: sex, age, severity of deficit at entry and at day 7, level of consciousness at entry, time after symptom onset, history of smoking, history of hypertension, diabetes, myocardial infarction, atrial fibrillation, rheumatic heart disease, dilated cardiomyopathy, all potential cardioembolic sources, presence of a consistent lesion on computed tomography at entry and at days 5-9, and the size of such lesion. RESULTS: All entry criteria were met by 172 patients. Age > or = 70 years, a Canadian Neurological Scale score < 6.5 at entry and at day 7, atrial fibrillation, presence of a potential cardioembolic source, and a "large" lesion (involving more than half the cerebral lobe) on computed tomography at days 5-9 were associated with a significantly worse outcome both at 30 days and at 6 months. After multivariate analysis, a Canadian Scale score < 6.5 at entry (p < 0.0001) and atrial fibrillation (p = 0.005) were associated with a significant handicap or death at 30 days, whereas only a Canadian Scale score < 6.5 (p < 0.0001) was associated with a worse prognosis at 6 months. An association of age > or = 70 years with a worse outcome at 6 months was of borderline significance (p = 0.054). CONCLUSIONS: Some prognostic indicators are available during the first few hours after onset of a carotid ischemic stroke and may be useful in the stratification of patients in clinical trials. Severity of deficit is the most important indicator, whereas the presence of atrial fibrillation worsens the prognostic outlook with respect to early handicap but not mortality. PMID- 8465358 TI - Questions people ask about stroke. AB - BACKGROUND AND PURPOSE: We sought to identify the type and frequency of questions asked about stroke by patients, relatives, and caregivers. METHODS: All stroke related inquiries made to Stroke Association Advice Centers in the United Kingdom during a 4-month period were recorded. RESULTS: During the study period, 1,397 people asked 1,908 questions. Nearly one quarter needed more information about the nature of stroke. The other most common inquiries concerned help at home (with many expressing concern about their current level of community support), requests for information about stroke clubs, speech difficulties, rehabilitation, personality changes, and depression. CONCLUSIONS: Knowledge of the questions asked should enable health professionals to provide better information to stroke victims and allow modification of stroke information pamphlets. PMID- 8465359 TI - Anterior ischemic optic neuropathy is not associated with carotid artery atherosclerosis. AB - BACKGROUND AND PURPOSE: The relation between anterior ischemic optic neuropathy and carotid artery atherosclerotic disease is unclear. We studied patients with anterior ischemic optic neuropathy to determine if they had an increased occurrence of carotid artery stenosis. METHODS: Fifteen consecutive patients with anterior ischemic optic neuropathy were evaluated prospectively for cervical carotid artery stenosis and compared with 30 age- and sex-matched asymptomatic patients and also with 11 age- and sex-matched patients experiencing transient monocular blindness. RESULTS: There was no difference in the mean stenosis of the internal carotid artery between patients with anterior ischemic optic neuropathy (mean carotid stenosis, 19%) and asymptomatic patients (mean carotid stenosis, 9%; p > 0.05), whereas patients with transient monocular blindness had significantly more stenosis (mean, 77%) in the cervical carotid arteries than both control subjects (p < 0.0001) and patients with anterior ischemic optic neuropathy (p < 0.0001). There was also no difference in the percentage of patients with stenosis > or = 30% in anterior ischemic optic neuropathy (two of 15) and asymptomatic patients (five of 30), whereas 10 of 11 patients with transient monocular blindness had stenoses > or = 30%, significantly more than patients with anterior ischemic optic neuropathy (p < 0.0001) and asymptomatic patients (p < 0.0001). CONCLUSIONS: Anterior ischemic optic neuropathy is not a marker for atherosclerotic carotid artery stenosis. The pathogenesis of nonarteritic anterior ischemic optic neuropathy does not involve carotid artery stenosis in most patients. PMID- 8465360 TI - Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. The Dutch TIA Trial Study Group. AB - BACKGROUND AND PURPOSE: beta-Blockers prevent vascular events in patients after myocardial infarction and lower blood pressure, the main risk factor for stroke. Hence, we assessed the effects of atenolol on the occurrence of death from vascular causes, stroke, or myocardial infarction and on blood pressure in patients after a transient ischemic attack or nondisabling ischemic stroke. METHODS: In a double-blind, placebo-controlled randomized clinical trial we studied the occurrence of the outcome event death from vascular causes, nonfatal stroke, or nonfatal myocardial infarction and the outcome event fatal or nonfatal stroke as well as blood pressure on follow-up. A total of 1,473 aspirin-treated patients with transient ischemic attack or nondisabling ischemic stroke were randomized to 50 mg atenolol daily or placebo. The mean follow-up was 2.6 years. RESULTS: Patients on atenolol had a risk of 97/732 (13.3%) for the combined outcome event versus a risk of 95/741 (12.8%) for those on placebo (adjusted hazard ratio, 1.00; 95% confidence interval, 0.76-1.33). The adjusted hazard ratio for fatal or nonfatal stroke was 0.82 (95% confidence interval, 0.57-1.19). More patients on beta-blocker (153) reported adverse effects than on placebo (103). At the first follow-up visit after randomization (median at 4 months) systolic blood pressure in the atenolol group had dropped by 8.0 mm Hg compared with 2.2 mm Hg in the placebo group (difference, 5.8 mm Hg; 95% confidence interval, 2.9-8.6 mm Hg). For diastolic blood pressure this difference was 2.9 mm Hg (95% confidence interval, 1.5-4.4 mm Hg). CONCLUSIONS: Our data neither confirm nor rule out that atenolol prevents important vascular events in patients after transient ischemic attack or nondisabling ischemic stroke, given the modest effect on blood pressure, the restrictions in patient selection, and the limited number of patient-years. PMID- 8465361 TI - Angiographic evaluation of brain infarction limited to the anterior cerebral artery territory. AB - BACKGROUND AND PURPOSE: Brain infarction localized in the anterior cerebral artery territory is rather uncommon, and its etiology has not yet been fully elucidated. METHODS: Based on computed tomographic findings, 17 patients with solitary anterior cerebral artery territory infarction were selected from among 3,619 patients admitted consecutively to our institute. Patients without angiographic examinations were excluded. The angiographic findings and clinical category of stroke were analyzed in each patient. RESULTS: Angiographic abnormalities were revealed in all patients. These consisted of occlusive changes (n = 10) or reversible segmental dilatation (n = 3) of the anterior cerebral artery, A1 hypoplasia (n = 5), and occlusive changes of the carotid artery (n = 3). In one patient with anterior cerebral artery occlusion, the occluded artery was reopened and subsequently became reoccluded. The clinical category of stroke was classified as atherothrombotic in 10 patients, cardioembolic in three, and undetermined in the remaining four. In eight of the 10 patients with atherothrombotic infarction, the anterior cerebral artery was narrowed or occluded. In all patients with cardioembolic infarction, the A1 segment contralateral to the infarction was hypoplastic. CONCLUSIONS: In our series, solitary anterior cerebral artery territory infarction was attributable most commonly to local atherothrombosis and occasionally to cardiogenic embolism. A hypoplastic A1 segment may facilitate the occurrence of embolism in the anterior cerebral artery. Reversible dilatatory and occlusive changes of this artery may be another important cause of infarction. PMID- 8465362 TI - Intracerebral hemorrhage after fibrinolytic therapy for acute myocardial infarction. AB - BACKGROUND AND PURPOSE: Intracerebral hematoma may complicate treatment of acute myocardial infarction in patients treated with fibrinolytic agents. We studied the clinical presentation and computed tomographic characteristics. METHODS: We studied eight patients with lobar intracerebral hematomas after fibrinolytic treatment of acute coronary occlusion. All patients had electrocardiographic and laboratory evidence of acute myocardial infarction and were treated with tissue plasminogen activator or streptokinase followed by heparin infusion to prevent reocclusion. Computed tomography scans of 17 patients with cerebral hemorrhage from other causes were used for comparison. RESULTS: For most patients, outcome was fatal within hours of the ictus. Computed tomography scans showed superficially large lobar hematomas in six patients. One patient had a putaminal hemorrhage, and one had a vermis hemorrhage. Multiple sites of intracerebral hemorrhage were noted in three patients. Fluid levels inside the hematoma suggesting continuing hemorrhage into multiple compartments were common. Radiologically, fluid levels in hematomas, multiple hematomas, and blood in multiple compartments served to differentiate fibrinolysis-induced hemorrhage from hemorrhage of other causes. Severe amyloid angiopathy was found in one patient who was operated on. CONCLUSIONS: Hemorrhages in multiple compartments and the presence of fluid levels inside the hematoma suggest fibrinolysis associated cerebral hematomas. Severe amyloid angiopathy may be a crucial factor in this clinical entity. Outcome is poor, and a high proportion of patients have rapid progression to brain death. Therefore, emergency neurosurgical evacuation will probably be unsuccessful. PMID- 8465363 TI - Transforming growth factor-beta 1 reduces infarct size after experimental cerebral ischemia in a rabbit model. AB - BACKGROUND AND PURPOSE: The aim of this study was to examine the effect of transforming growth factor-beta 1, a cytokine shown to amelioriate cardiac ischemia, in a rabbit model of thromboembolic stroke. METHODS: An autologous clot embolus was introduced intracranially through the right internal carotid artery in 21 New Zealand White rabbits, with seven in each group receiving either vehicle control (albumin) or 10 or 50 micrograms transforming growth factor-beta 1 administered as an intracarotid bolus immediately before autologous clot embolization. Multiple physiological parameters were monitored, including regional cerebral blood flow, arterial blood gases, hematocrit, glucose, core temperature, and mean arterial pressure. The brain was harvested 4 hours after embolization, and infarct size was determined planimetrically as a percentage of the entire hemisphere. RESULTS: Brain infarct size was reduced in both the 10 microgram (16.7 +/- 4.0% [mean +/- SEM], p < 0.05) and 50-microgram (21.7 +/- 4.5%) transforming growth factor-beta 1-treated groups when compared with the control group (31.9 +/- 6.6%). Regional cerebral blood flow did not show any significant intergroup or intragroup variation over time, although the 10 microgram transforming growth factor-beta 1 group experienced a greater return of cerebral blood flow in the first 2 hours after embolization. CONCLUSIONS: Transforming growth factor-beta 1 reduced brain infarct size in a rabbit model of thromboembolic stroke. This effect was not related to a direct effect on blood flow. Studies are ongoing to determine the mechanism by which transforming growth factor-beta 1 salvages ischemic brain. PMID- 8465364 TI - Cerebral blood flow alterations in a rat model of cerebral sinus thrombosis. AB - BACKGROUND AND PURPOSE: Outcome from sinus vein thrombosis is very variable, with symptoms from headache to coma. Experimental findings suggest that an involvement of cortical veins is necessary to affect the cerebral microcirculation. Laser Doppler flowmetry was used to investigate the regional and temporal changes in local cortical blood flow after experimental occlusion and thrombosis of the superior sagittal sinus and tributary cortical veins in rats. METHODS: Thrombosis was induced by slow injection of kaolin-cephalin suspension after frontal and caudal ligation of the sagittal sinus in rats. Local cerebral blood flow was measured by laser Doppler flowmetry and correlated with parenchymal damage found 24 hours after induction of thrombosis. RESULTS: Local cerebral blood flow 1 hour after sinus occlusion and induction of thrombosis had decreased to 60.92 +/- 29.05% (p < 0.01); however, there was a large variability among individual animals. Only five of 12 rats showed histological damage and intracerebral hemorrhages 24 hours after induction of thrombosis. A subgroup analysis revealed that parenchymal damage occurred in concurrence with reduced blood flow values after sinus ligation and injection of the thrombogenic material. Sinus thrombosis alone, without alteration of blood flow, did not cause tissue necrosis. CONCLUSIONS: The data support the contention that sinus vein thrombosis evolves gradually, with major symptoms occurring only if the thrombus expands from the sinus into bridging and cortical veins. Collateral venous outflow pathways are thereby occluded, and local blood flow may become reduced to and below the ischemic threshold. PMID- 8465365 TI - Isolated or predominant ocular motor nerve palsy as a manifestation of brain stem stroke. AB - BACKGROUND AND PURPOSE: There have been few reports of strokes producing isolated or predominant ocular motor nerve palsies as a clinical manifestation. METHODS: We studied seven patients with brain stem stroke who had ocular motor palsies as the only or the predominant neurological manifestation, and we correlated their clinical features with radiological findings. RESULTS: Five patients had small strokes in the area of oculomotor nuclei or fascicles and showed various combinations of oculomotor disturbances. Three of these patients showed vertical gaze paresis of the opposite eye. One patient with a small hemorrhage near the aqueduct of Sylvius showed fourth nerve palsy on the contralateral side, and a patient with a small infarct in the pontine tegmentum showed isolated sixth nerve palsy. Nonocular minor neurological signs included trigeminal sensory changes in four patients and clumsy arm in two. Ocular and nonocular dysfunctions generally improved within several months. Radiological findings of the brain stem correlated well with the ocular signs. CONCLUSIONS: We conclude that acute brain stem stroke should be included in the differential diagnosis of isolated ocular motor nerve palsies and that appropriate diagnostic investigations should be performed in these cases. PMID- 8465366 TI - Myocardial infarction, thrombolytic therapy, and stroke. A community-based study. The MITI Project Group. AB - BACKGROUND: Thrombolytic therapy used in patients with acute myocardial infarction may increase the risk of stroke. Scant information is available from community-based studies. SUMMARY OF REPORT: Among 5,635 consecutive patients admitted with acute myocardial infarction to hospitals in Seattle and surrounding suburban King County, Washington, 116 (2.1%) experienced strokes during hospitalization. Of these strokes, 82 (71%) were ischemic and 34 (29%) were hemorrhagic, defined by a patient's having had a computed tomographic scan of the head that showed blood. Thrombolytic therapy was given to 1,413 of these patients (25%) and was associated with increased risk of hemorrhagic stroke but reduced risk of ischemic stroke. The relative risk of stroke with thrombolytic therapy was estimate using multiple logistic regression to adjust for potential confounding factors. The adjusted relative risk for hemorrhagic stroke was 3.6 (95% confidence interval [CI], 1.7-8.0); for ischemic stroke, 0.4 (95% CI, 0.2 0.9); and for overall stroke, 1.0 (95% CI, 0.6-1.7). The adjusted risk for death from any cause following stroke was 3.0 (95% CI, 1.4-6.4). CONCLUSIONS: Although thrombolytic therapy had little effect on the overall occurrence of stroke, thrombolytic therapy increased the risk of stroke death because more patients with hemorrhagic than ischemic strokes died during their hospitalization. The rates of hemorrhagic stroke with thrombolytic therapy reported in the present study are higher than those reported in clinical trials in which treatment is given to select patients under strict protocols. PMID- 8465367 TI - Dynamic computed tomographic imaging of regional cerebral blood flow and blood volume. A clinical pilot study. AB - BACKGROUND AND PURPOSE: The advent of faster computed tomography scanners has evoked considerable interest in using this technology as a more practical method of regional cerebral hemodynamic evaluation than the currently available positron emission and single-photon emission computed tomography. The theoretical concepts have been worked out and validated in the laboratory by several groups. The aim of the present study was the development of a clinically useful system. METHODS: Software was developed for dynamic computed tomography-based calculation and color-coded representation of regional cerebral blood flow and blood volume. Normal values, reproducibility, and sensitivity to acetazolamide challenge were established in 13 volunteers. The method was applied to an additional three patients with internal carotid artery occlusion and known decreased vascular reserve capacity as diagnosed by transcranial Doppler ultrasonography. RESULTS: Normal regional cerebral blood flow was determined as 50 +/- 13 ml/100 ml per minute and normal fractional cerebral blood volume as 58 +/- 12 ml/1,000 ml (mean +/- SD). In five volunteers, two examinations were performed within 15 minutes for determination of reproducibility. Intermeasurement variability of hemispheric blood flow and blood volume was determined as +/- 23% and +/- 16%, respectively. Intravenous administration of 1 g acetazolamide resulted on the average in a 75% increase of blood flow and a 65% increase of fractional blood volume. In the patients with decreased cerebrovascular reserve capacity, baseline fractional blood volume in the ischemic hemispheres was significantly increased. Baseline regional cerebral blood flow in the ischemic territories was overestimated. Reactivity to acetazolamide of both regional blood flow and fractional blood volume was clearly reduced in the ischemic hemispheres. CONCLUSIONS: The present results demonstrate that the method is a simple and effective means of determining regional cerebral blood volume. Spatial resolution is superior to that of the radioactive tracer methods. Hemodynamic evaluation of ischemic conditions can be performed on the basis of increased resting cerebral blood volume and a diminished increase after acetazolamide. Accuracy of cerebral blood flow measurements, on the other hand, is affected by abnormal cerebral blood volume, and corresponding adjustments need to be made in pathological conditions. PMID- 8465368 TI - Recurrent ischemic events in two patients with painless vertebral artery dissection. AB - BACKGROUND AND PURPOSE: Vertebral artery dissection causes endothelial changes and stenosis that may lead to recurrent ischemic neurological events. The diagnosis may not be obvious because the dissection may be painless and "spontaneous" (no obvious trauma). Magnetic resonance angiography has increasingly been used to screen patients for this disorder, but its accuracy has not yet been established. CASE DESCRIPTION: Two patients were admitted with repeated transient ischemic attacks and strokes over 11 months and 1 month, respectively. Neither had a history of trauma, cervical pain, or headache. Magnetic resonance angiography failed to visualize vertebral artery dissections that were later revealed by conventional angiography. One patient's events were stopped by balloon occlusion of the vertebral artery proximal to the posterior inferior cerebellar artery branch. CONCLUSIONS: Magnetic resonance angiography is not yet sensitive enough to always visualize vertebral artery dissection. Vertebral artery dissection is a life-threatening condition that requires aggressive evaluation and treatment. PMID- 8465369 TI - An unusual cause of cerebral venous thrombosis in a four-year-old child. AB - BACKGROUND AND PURPOSE: Inherited protein S deficiency has been associated with an increased risk of thromboembolic disease. It is possible that such a coagulopathy could predispose children to the development of strokes by permitting clot formation in response to stimuli that ordinarily would be insufficient to cause thrombus formation. CASE DESCRIPTION: We evaluated a previously well 4-year-old boy who developed cerebral venous thrombosis after suffering minor head trauma. Crossed-immunoelectrophoresis of his plasma showed a marked decrease of the free, active form of protein S. Family studies revealed that the patient's father and other paternal relatives had a similar abnormality of protein S. CONCLUSIONS: We suggest that the cerebral venous thrombosis in this child was initially precipitated by minor head trauma and pathological thrombus formation was then potentiated by inherited protein S deficiency. This case extends the clinical spectrum for protein S deficiency and emphasizes the importance of evaluating family members to establish a specific diagnosis and therapeutic intervention. PMID- 8465370 TI - Evidence for embolization from a posterior cerebral artery thrombus by transcranial Doppler monitoring. AB - BACKGROUND: Transcranial Doppler monitoring enables the detection of emboli passing through intracranial arteries. Comparison of the different intracranial vessels with respect to emboli detection can be of use in identifying the source of embolism. CASE DESCRIPTION: We report the case of a patient with an acute posterior cerebral artery (PCA) infarct on the right side, with evidence for high degree ipsilateral PCA narrowing on admission. During transcranial Doppler monitoring 3 days later, we found frequent emboli-like signals in the power spectrum of the right PCA distal to the stenosis but not in any other intracranial vessels. Four days later, angiography and transcranial Doppler failed to show PCA narrowing, and transcranial Doppler monitoring of the right PCA showed no further emboli-like signals. A stenosis of the right vertebral artery was regarded as the possible source of thromboembolic narrowing of the PCA. CONCLUSIONS: We assume that in our patient a thrombotic clot in the PCA was resolved autolytically through detachment of small emboli into the distal part of the PCA. We speculate that in the early course of autolysis a larger fragment of the clot had occluded one of the distal branches, thus leading to the small PCA territory infarct. PMID- 8465371 TI - Current role of electroencephalography in cerebral ischemia. AB - BACKGROUND: The electroencephalogram has been largely supplanted by neuroimaging techniques for the diagnosis and localization of ischemic stroke. However, because of its close correlation with cerebral metabolism and its ability to detect brief transient alterations in cortical function, the electroencephalogram may still be useful for certain diagnostic applications in stroke. SUMMARY OF REVIEW: The relation of electroencephalographic phenomena to cerebral blood flow and metabolism is reviewed. Ten clinical questions that can be addressed by the electroencephalogram in patients with stroke are posed. The presence of seizures, confirmation of diagnosis, intraoperative monitoring, and level of consciousness are areas of proven usefulness. The electroencephalogram provides less worthwhile information about the time course, prognosis, and localization of strokes. Computerized techniques are of potential but unproven value. CONCLUSIONS: The electroencephalogram retains a worthwhile place in the evaluation of patients with cerebral ischemia when it is used to answer specific questions. All patients with strokes do not need electroencephalograms, but the test can provide uniquely useful data in some. PMID- 8465372 TI - Secular trends in stroke incidence and mortality. PMID- 8465373 TI - Simultaneous bihemispherical assessment of cerebral blood flow velocity changes during a mental arithmetic task. PMID- 8465374 TI - Middle cerebral artery embolism and unilateral visual loss after autologous fat injection into the glabellar area. PMID- 8465375 TI - Perinatal health in developing countries. PMID- 8465376 TI - Phlebotomus (Phlebotomus) duboscqi (Diptera: Phlebotominae), naturally infected with Leishmania major in southern Ethiopia. AB - In a survey of Leishmania infections in phlebotomine sandflies in visceral leishmaniasis focus at Aba Roba, Segen Valley, southern Ethiopia, Phlebotomus duboscqi was found naturally infected with L. major (zymodeme MON-74). This is the first isolation of L. major from a vector sandfly in Ethiopia, from an area where human and/or rodent infections with L. major are, so far, unknown. PMID- 8465377 TI - Use of 'original antigenic sin' theory to determine the serotypes of previous dengue infections. AB - Determination of serotypes of dengue viruses involved in sequential infections is important since, according to a theory of the pathogenesis of dengue haemorrhagic fever, a particular serotype may be a risk factor. It has been reported in Asia that at least the serotypes involved in the first infections could be serologically identified by the plaque reduction neutralization test (PRNT) because the highest PRNT titres after the second infections corresponded to the serotypes in the first infections. We re-examined the application of this theory of 'original antigenic sin' in Puerto Rico to evaluate its utility in serodiagnosis. Our results showed that it could not be applied reliably because of discrepant results. PMID- 8465378 TI - Immune activation in human rabies. AB - Serum cytokines were compared by enzyme-linked immunosorbent assay among (i) 28 patients with rabies, (ii) 13 patients with non-fatal encephalitis due to other viruses, (iii) 16 patients with immune-mediated neurological diseases, and (iv) 15 patients with non-viral central nervous system infections and non-HTLV-I progressive spastic paraparesis. Levels of soluble interleukin 2 receptor (S IL2R) were comparable in groups (i)-(iii). Fewer paralytic (1/6) than encephalitic (12/22) rabies patients had elevated S-IL2R. Only one patient with rabies and one with non-fatal viral encephalitis (group ii) had elevated S-CD8. Interleukin 6 (IL-6) was elevated in 5/22 rabies patients with encephalitis and in 0/6 paralytic rabies patients. Four individuals in groups (ii) and (iii) had elevated IL-6. Patterns of cytokine responses in group (iv) were similar to those in groups (i)-(iii). The results suggest defects in immune responsiveness in paralytic rabies. PMID- 8465379 TI - The effect of nutritional supplementation and stunting on morbidity in young children: the Jamaican study. AB - Infection and undernutrition in young children are thought to act synergistically. However, studies of the relationship between low height-for age (stunting) and morbidity in young children have had inconsistent findings and there are few adequate data on the effects of nutritional supplementation on morbidity. 129 stunted and 21 non-stunted children aged between 9 and 24 months, from poor Kingston neighbourhoods, identified from a house-to-house survey, were studied. The stunted children were randomly assigned to supplementation or no supplementation. Every week for 24 months the mothers were asked about the occurrence of any symptoms of illness. Supplementation had no consistent effect on the incidence or duration of symptoms. The stunted children had significantly more attacks of diarrhoea, fever, anorexia and apathy than the non-stunted children. The differences remained after controlling for social background and previous attacks of diarrhoea. There was also some indication of more severe illness in the stunted than in the non-stunted children. PMID- 8465380 TI - Urban beri-beri in The Gambia, west Africa. AB - Thirty-eight patients with beri-beri (13 dry, 14 wet and 11 mixed type) were seen at the Royal Victoria Hospital, Banjul, The Gambia, in 1990-1991, with a peak in September-October (25 cases) during the latter half of the rainy season. They were all non-confined residents of urban areas. Overt risk factors were pregnancy (6), alcohol (5), fevers (4), chronic disability (4), and exercise (2). Four patients (10.5%) died. The potential for large outbreaks of beri-beri exist in many urban areas of West Africa where polished rice is the staple diet. PMID- 8465381 TI - Discriminatory ability of typing systems in Leishmania. PMID- 8465382 TI - Chagas disease in north-west Argentina: association between Trypanosoma cruzi parasitaemia in dogs and cats and infection rates in domestic Triatoma infestans. AB - The association between Trypanosoma cruzi parasitaemia in dogs and cats and Tryp. cruzi infection rates in domestic Triatoma infestans was studied in a cross sectional survey of 31 houses (89%) in the rural villages of Trinidad and Mercedes, north-west Argentina, where no spraying of insecticides had ever been done. Similar prevalence rates of parasitaemia, determined by xenodiagnosis, were recorded among 68 dogs (41.2%) and 28 cats (39.3%). Bug infection rates were significantly associated with the presence of infected cats (those with positive xenodiagnosis) stratified by the number of infected dogs (relative risk = RR = 1.90; 95% confidence interval = CI = 1.51-2.38), and with the number of infected dogs stratified by the presence of infected cats (RR = 2.71; CI = 1.81-4.07). The percentage of infected bugs in houses with and without children stratified by the presence of infected dogs or cats was not significantly different (RR = 0.69; CI = 0.45-1.05). The combined effect of infected dogs and infected cats on bug infection rates fitted closely with an additive transmission model. Bug infection rates were significantly higher when infected dogs shared the sleeping areas of people than when they did not (RR = 1.79; CI = 1.1-2.91). Our study showed that infected dogs and infected cats increase the risk of domestic transmission of Tryp. cruzi to T. infestans. PMID- 8465383 TI - A Melanesian sciapod. PMID- 8465384 TI - Relationship between the degree of poverty and the IgE response to Ascaris infection in slum children. AB - We examined a group of urban slum children in Caracas, Venezuela, and demonstrated the relationship that exists between poverty, conditions of hygiene and the prevalence of helminth infection. Concordant with the high prevalence of helminth infection in these children, the total serum levels of immunoglobulin E (IgE) and blood eosinophilia were elevated and were directly related to the degree of poverty and lack of sanitary facilities. However, in contrast, the reverse pattern was observed for the specific allergic response to these parasites. Thus, the immediate hypersensitivity skin test reactivity to Ascaris antigens, and the serum levels of specific anti-Ascaris IgE antibody, were lowest in the poorest children, who had the highest prevalence of helminth infection and the highest total IgE levels. As allergic-type reactions may participate in protective mechanisms against helminths, these results suggest that poverty and poor sanitary conditions may, by influencing the IgE response, compromise the resistance of such children to parasitic infections. PMID- 8465385 TI - Prevalence of antibody to Helicobacter pylori in children in northern Nigeria. AB - Helicobacter pylori infection is common in northern Nigeria, but the age of acquisition is unknown. In a prospective study, immunoglobulin G antibodies to H. pylori were measured in 143 children under the age of 20 years. Ninety-one percent of 43 randomly chosen subjects over 10 years had antibodies to H. pylori. A further 100 children under 10 years presenting to the University of Maiduguri Teaching Hospital were also tested. Sixty-nine percent had antibodies, including 58% of those aged under 1 year. H. pylori infection is acquired at an early age, and in this study was not associated with any other pathology. This study was carried out in an area where peptic ulceration and gastric cancer are uncommon. The early acquisition of H. pylori infection may be important in relation to its apparent lack of pathogenicity. PMID- 8465386 TI - Population growth, fertility, mortality and migration in drought prone areas in Ethiopia. AB - To assess the population dynamics of drought-prone communities, we investigated 605 households in the pastoralist Boran community of Dubluk and in the agricultural community of Elka, both located in southern Ethiopia. The age and sex composition of the population as well as records of births, deaths and patterns of migration were observed for 2 consecutive years. Repeated surveys of the same households revealed much higher rates for deaths and births than did cross-sectional surveys with a one-year recall period. Indirect mortality estimates showed that the under 5 years mortality rates (per 1000 births) were 135 in Dubluk and 219 in Elka. Highest crude death rates were observed in Elka during periods of meningitis and malaria epidemics. During the period of observation, death rates fluctuated to a greater extent than birth rates. Both communities had very high rates of natural increase: in Dubluk 39.0/1000 and in Elka 37.1/1000. In Dubluk, this rate was far higher than any previously recorded and may have indicated that fertility regulating mechanisms, traditionally inherent in the pastoralist social organization, had become weaker as part of cultural changes. Dubluk represented a semi-nomadic society with a moderately high mobility pattern. Peak periods of migration coincided with times of food scarcity in Elka. PMID- 8465387 TI - The development and validation of a simple antigen detection ELISA for Plasmodium falciparum malaria. AB - A double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) is described for the detection of Plasmodium falciparum antigen. The test is based on an immunoglobulin (Ig) M capture monoclonal antibody on the solid phase and an IgG monoclonal antibody conjugated to peroxidase. The simple test takes about 2.5 h to complete and, because it uses whole blood with no prior treatment, it is possible to process batches of 50-100 samples simultaneously. The test is specific to P.falciparum and has a sensitivity close to that usually achieved with Giemsa-stained blood films. The reagents employed are stable at refrigerator temperatures for over 6 months, and as the test is compatible with human immunodeficiency virus and hepatitis B surface antigen ELISAs it could be suitable for blood transfusion screening. PMID- 8465388 TI - Infectivity of Plasmodium vivax and P. falciparum to Anopheles tessellatus; relationship between oocyst and sporozoite development. AB - The assessment of malarial infectivity, for example in the evaluation of transmission blocking immunity, is generally based on counting oocysts in mosquitoes fed on infected blood. Ultimate transmission of the disease may, however, depend on the sporozoite load in the mosquito and its relationship to the size of the inoculum introduced to man. We conducted a laboratory study on Anopheles tessellatus infected with 108 different natural isolates of Plasmodium vivax from patients and 24 of P. falciparum to determine the relationship between oocyst numbers, sporozoite loads, and the effect of these on mosquito mortality. It was found that the P. vivax parasite density was positively correlated with the proportion of mosquitoes infected by a given feed at both the midgut and gland stages of parasite development (correlation coefficient [r] = 0.77, P < 0.001 and r = 0.6, P < 0.05 respectively). A significant positive linear correlation was observed between the number of oocysts and sporozoites in P. vivax (r = 0.5; P < 0.05); the proportions of mosquitoes infected with oocysts and sporozoites were also similarly related, although in general about 15% of mosquitoes infected with oocysts failed to develop salivary gland infections with sporozoites. The number of mosquitoes infected with P. falciparum parasites was too low for statistical analysis. Infection with either species of parasite did not appear to affect mosquito survival, nor was parasite density in the mosquito correlated with mosquito mortality. PMID- 8465389 TI - Field study of an antigen-detection ELISA specific for Plasmodium falciparum malaria. AB - We field-tested a specific antigen-detection enzyme-linked immunosorbent assay (ELISA) based on the histidine-rich protein of Plasmodium falciparum, in a district hospital in Thailand. The test was simple to perform, takes less than 3 h to complete, can deal with batches of sera, be read visually, and was 98.05% sensitive and 96.22% specific. However, 3 of 154 microscopically identified P. falciparum cases gave false negative ELISA results. One of these patients had been admitted to hospital for P. falciparum malaria 3 months previously and all 3 came from hyperendemic villages and were thought to have had previous episodes of malaria, possibly resulting in high titres of circulating blocking antibody. The test was more sensitive when whole blood was frozen and thawed before testing. This test is promising but requires further refinement to eliminate false negatives before it can be used safely for screening acutely ill patients for falciparum malaria. The sensitivity of this ELISA appears to be sufficiently high to consider it as a tool for blood donor screening in regions with a high prevalence of P. falciparum carriers with low parasitaemia. There is at present no satisfactory routine screening method for large numbers of blood donors for malaria. PMID- 8465390 TI - Autoantibodies give false positive reactions in the serodiagnosis of Trypanosoma cruzi infection. PMID- 8465391 TI - Enzyme-linked immunosorbent assay for the detection of anti-Giardia specific immunoglobulin G in filter paper blood samples. AB - Conventional diagnosis of infection with Giardia duodenalis is by faecal examination but the sensitivity of a single examination is low. Serological tests, although not always positive, are more acceptable to patients and are useful in determining the prevalence of giardiasis in large populations. We show here that blood collected on filter paper and dried provides an excellent source of material for enzyme-linked immunosorbent assays; using samples from a group of 88 stool-negative and 45 positive patients, the optimum results were obtained by taking the control mean optical density plus one standard deviation as the negative/positive cut-off value. The sensitivity was 91% (2/45 false negatives), and the specificity 95% (4/88 false positives). This method should be particularly useful for large-scale surveys in developing countries or wherever serological testing is done in central laboratories. PMID- 8465392 TI - A field and laboratory evaluation of a commercial ELISA for the detection of Giardia coproantigens in humans and dogs. AB - A capture enzyme linked immunosorbent assay (CELISA) was evaluated for its ability to detect Giardia coproantigens in the faeces of humans and dogs in the Perth metropolitan area and Aboriginal communities in Fitzroy Crossing, Western Australia. Using zinc sulphate flotation and light microscopy, Giardia cysts and/or trophozoites were observed in 8 of 57 (14%) human stool samples from Perth and 21 of 55 (38%) stool samples from Fitzroy Crossing, after 2 separate examinations. Analysis of diagnostic sensitivity using the ELISA revealed that coproantigens were detected in all 29 human samples (100%) in which Giardia cysts and/or trophozoites were also present. Coproantigens were detected in one further sample from Perth and in 3 samples from Fitzroy Crossing in which no Giardia cyst or trophozoite was observed. The specificity of the test, as defined using Fitzroy Crossing samples free from Giardia, was 91%. The assay did not cross react with Giardia-free stool samples containing Hymenolepis nana, Entamoeba coli, E. hartmanni, Chilomastix mesnili or Ancylostoma duodenale. Giardia cysts and/or trophozoites were also observed in 11 of 32 dog faecal samples (34%) in Perth and 11 of 29 dog samples (38%) in Fitzroy Crossing, after one zinc sulphate examination. The sensitivity of the ELISA for dogs was 64% and 55% for Perth and Fitzroy Crossing specimens respectively. The specificity was 95% when Fitzroy Crossing samples were used. Other parasites observed in Giardia-free faecal samples from dogs which did not produce a positive reaction with the kit were Ancylostoma caninum, Sarcocystis sp. and Isospora sp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465393 TI - Seroepidemiology and serodiagnosis of schistosomiasis in Kenya using crude and purified egg antigens of Schistosoma mansoni in ELISA. AB - The performance of antibody detection for the diagnosis of schistosomiasis has been evaluated in Kenya. Approximately 1500 blood samples from 3 areas with endemic schistosomiasis (Schistosoma mansoni only, S. haematobium only, and a mixed infection area), and from a non-endemic control area, were tested for their antibody reactivity in an enzyme-linked immunosorbent assay (ELISA). The results were compared with infection status determined by parasitological examination. Two test antigens were used: unfractionated S. mansoni egg homogenate (SEA), and CEF6, a previously described, partially purified fraction of SEA containing 2 cationic antigens. The antigens prepared from eggs of Kenya and Puerto Rico S. mansoni isolates gave very similar results. Bloods from patients with S. haematobium infection cross-reacted significantly with the two S. mansoni antigen preparations, but reactivity against CEF6 appeared more specifically indicative of S. mansoni infection. Of 254 blood samples from schoolchildren in the non endemic area, 100% gave ELISA optical density readings at 492 nm (OD492) < 0.20 against SEA, and 98% were < 0.20 against CEF6. With 887 blood samples from subjects of all ages in the area endemic for S. mansoni alone, using an ELISA OD492 cut-off point of 0.20, SEA and CEF6 had sensitivities of 94% and 97% respectively, and specificities of 64% and 59% respectively. Increasing the OD492 cut-off value reduced the sensitivity and increased the specificity of both test antigens. Specificity of both antigens was poor with samples from 234 children in an area endemic for both S. mansoni and S. haematobium (< 20% for both antigens at an OD492 cut-off value of 0.20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465394 TI - Serum ionized calcium, serum and intracellular phosphate, and serum parathormone concentrations in acute malaria. AB - Previous studies have shown depressed serum corrected calcium and phosphate concentrations in acute falciparum malaria. To characterize malaria-associated disturbances in mineral homoeostasis further, serum ionized calcium and intracellular phosphate were measured in 18 patients (10 with falciparum malaria, 8 with vivax malaria) and 10 healthy controls. Six patients (4 falciparum, 2 vivax) had admission serum ionized calcium concentrations below the absolute control range (< 1.15 mmol/litre) and a further six (3 falciparum, 3 vivax) developed ionized hypocalcaemia during treatment. The patients with falciparum malaria had the lowest values at presentation (median [95% confidence intervals in brackets]: 1.17 [1.12-1.23] vs. 1.20 [1.18-1.24] mmol/litre in controls, P = 0.035) in the presence of depressed simultaneous serum parathormone concentrations (1.2 [0.6-1.9] vs. 1.6 [1.1-2.6] pmol/litre; P = 0.05). Admission serum phosphate concentrations were lower in the malaria patients (P = 0.007 vs. controls), especially in those with falciparum malaria (0.85 [0.7-1.1] vs. 1.2 [1.1-1.3] mmol/litre in controls; P = 0.002); patients with falciparum malaria also had significantly lower intracellular phosphate than controls (0.74 [0.58 0.90] vs. 0.88 [0.66-1.04] mmol/litre red cells; P = 0.047). There was a weak association between serum corrected and ionized calcium in the malaria patients (rs = 0.31, n = 18, P > 0.1), but serum and intracellular phosphate correlated significantly (rs = 0.71, n = 17, P < 0.001) with a regression line slope of 0.49 and intercept of 0.27 mmol/litre of red cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465395 TI - Interleukin-8 and Plasmodium falciparum malaria in Thailand. PMID- 8465396 TI - Pneumocystis carinii pneumonia and tuberculosis in Tanzanian patients infected with HIV. PMID- 8465397 TI - Chlamydial infection in the Amazon region of Brazil. AB - The prevalence of antibodies to Chlamydia was determined in 9 population groups with different risk levels for sexually transmitted diseases in Belem, Para state, Brazil. 583 serum samples were examined by the indirect immunofluorescence test. The prevalence rates varied from 33.3% in patients attending a sexually transmitted disease clinic to 97.1% in Parakana Indians. One or more pathogens were found in 55 of 86 patients presenting a clinical picture of urethritis; C. trachomatis was isolated from 11% (6/55) of these cases by inoculation to McCoy cell cultures, accounting for 30% (6/20) of the cases of non-gonococcal urethritis. C. trachomatis was isolated from one of 28 female patients (3.6%) attending gynaecology and obstetrics outpatient clinics. The positive patients had no symptom or complaint that would have suggested the diagnosis. PMID- 8465398 TI - Two cases of HIV-associated cryptococcosis due to the variety gattii in Rwanda. PMID- 8465399 TI - Detection of clinically and epidemiologically significant strains of Escherichia coli in faeces from young children in the tropics. PMID- 8465400 TI - Accidental envenoming by a Gaboon viper (Bitis gabonica): the haemostatic disturbances observed and investigation of in vitro haemostatic properties of whole venom. AB - We report the successful treatment of envenoming by the Gaboon viper (Bitis gabonica) and include results of in vitro investigations of the haemostatic properties of the whole venom. The patient was admitted to casualty soon after the bite with chest tightness, dizziness, nausea and swelling at the site of the bite and was treated immediately with polyspecific antivenom, hydrocortisone, chlorpheniramine and antibiotics. Results of haemostatic investigations were essentially normal on admission but on day 3 the thrombin time became prolonged and was associated with significant hypofibrinogenaemia and elevated D-dimers. Factors V and VIII, antithrombin III and protein C levels and platelet number were not significantly reduced. The haemostatic disturbances persisted for more than 24 h despite treatment with blood products (16 units of cryoprecipitate, 2 units of fresh frozen plasma and 6 units of platelet concentrate). Resolution of the abnormalities occurred only after administration of a further dose of antivenom. The period of hypofibrinogenaemia occurred at a time when venom antigen was undetectable in plasma by enzyme-linked immunosorbent assay. Studies in vitro with whole venom and a panel of amidolytic substrates commonly employed for measurement of haemostatic proteins revealed significant activity of venom with substrates sensitive to kallikrein and plasmin. The venom inhibited washed platelet aggregation induced by collagen, thrombin, arachidonic acid and the calcium ionophore A23187 in a dose-dependent manner. PMID- 8465401 TI - Fifteen years of cutaneous and mucocutaneous leishmaniasis in Bolivia: a retrospective study. AB - This paper present the results of a retrospective study of cases of cutaneous and mucocutaneous leishmaniasis in Bolivia between 1975 and 1991. The total number of cases reported was 4058, 739 of which were mucous. Three different areas of endemic leishmaniasis are defined in Bolivia. PMID- 8465402 TI - Life-threatening bradycardia and hypotension in a patient with ciguatera fish poisoning. PMID- 8465403 TI - Choice of therapy for imported cases of falciparum malaria in children: a retrospective study of 100 cases seen in Marseilles, France. AB - We have carried out a retrospective study on 100 children in hospital in Marseilles, France with a diagnosis of Plasmodium falciparum malaria. On admission, the main clinical features were anaemia (90 cases), fever (83 cases, > 40 degrees C in 22 cases), hepatomegaly (44 cases), vomiting (29 cases), neurological signs (22 cases), thrombocytopenia (13 cases), hyperparasitaemia (6 cases), jaundice (4 cases), shock (1 case) and hypoglycaemia (1 case). Severe malaria, as defined by the World Health Organization Malaria Action Programme, was rare in our study (only 2 cases) and the prognosis was good (no death, no sequela). The search for neurological signs such as impaired consciousness, prostration or convulsions is an effective and simple way to diagnose potentially severe cases. In the presence of these signs, intravenous quinine treatment resulted in a shortened duration of fever (30 h instead of 63 h) and thereby avoided patients becoming worse. In children without neurological signs or persistent vomiting, oral therapy may be used even if there is high fever or hyperparasitaemia, but close surveillance is required. Patients treated with halofantrine or mefloquine had a shorter stay in hospital than those treated with chloroquine (mean = 4 d instead of 5.7 d). The resistance of some strains to chloroquine may explain this difference. PMID- 8465404 TI - Treatment of Plasmodium falciparum malaria with pyrimethamine-sulfadoxine: selective pressure for resistance is a function of long elimination half-life. AB - In an area of continuing transmission of Plasmodium falciparum on the Kenya coast, children treated with pyrimethamine-sulfadoxine experienced rapid parasite clearance, although a high proportion became reinfected within a short time. The frequency of pyrimethamine resistance in vitro in new infections was higher during the elimination phase of drug from a previous treatment. In infections which occurred at times when predicted residual drug concentrations were no longer inhibitory, incidence of pyrimethamine resistance was no different from the natural or background frequency. These results are discussed in terms of the selective pressure for resistance which is exerted by drugs with long elimination half-lives and a consideration of possible ways by which the problem might be addressed. PMID- 8465405 TI - Activity in vitro of the enantiomers of halofantrine. PMID- 8465406 TI - Halofantrine treatment of uncomplicated falciparum malaria with high parasitaemia. PMID- 8465407 TI - Reversal of mefloquine resistance with penfluridol in isolates of Plasmodium falciparum from south-west Nigeria. AB - The susceptibilities of isolates of Plasmodium falciparum from Nigeria and two reference cloned strains (D6 and W2) to mefloquine or chloroquine alone and in combination with either penfluridol, a piperidine analogue, or verapamil were determined using a modification of the semiautomated microdilution technique. Six of the isolates showed reduced susceptibility to mefloquine in vitro. The response of the 6 isolates was similar to that of the mefloquine resistant reference clone D6, with 50% inhibitory concentration (IC50) values = 3.29-9.72 ng/ml. Only 2 of the Nigerian isolates were sensitive to mefloquine (IC50 = 1.16 ng/ml and 2.62 ng/ml) and were similar to the reference mefloquine sensitive clone W2 (IC50 = 1.78 ng/ml). All the isolates tested were sensitive to chloroquine, with IC50 values = 1.5-3.04 ng/ml. Simultaneous incubation of the parasites with a constant sub-inhibitory concentration of penfluridol (5.0 x 10( 7)M) and mefloquine increased the susceptibility of the resistant parasites to mefloquine. Addition of the neuroleptic drug penfluridol did not alter the response of sensitive parasites to mefloquine or chloroquine. Similarly, addition of 1.0 x 10(-6)M verapamil did not affect the activity of mefloquine against the sensitive or resistant parasites. PMID- 8465408 TI - Albendazole as a treatment for infections with Giardia duodenalis in children in Bangladesh. AB - Albendazole, a broad spectrum anthelmintic recently shown to be active in vitro against Giardia duodenalis, was given at 4 different dosages and compared with metronidazole in the treatment of children in Bangladesh infected with Giardia. Three stools were collected over 10 d after treatment and examined microscopically. Albendazole was found to be effective: single doses of either 600 mg (n = 103) or 800 mg (n = 114) successfully treated 62% and 75% of infections, respectively; 400 mg given either once a day for 3 d (n = 116) or for 5 d (n = 115) successfully treated 81% and 95% of all infections, respectively. Albendazole given daily at 400 mg for 5 d was as effective as metronidazole, which cured 97% of infections (n = 230). Albendazole may thus be an alternative treatment for infections with Giardia, while the moderate efficacy of single doses may provide a benefit in addition to its effects on several species of intestinal helminths. PMID- 8465409 TI - Treatment of mixed Oesophagostomum and hookworm infection: effect of albendazole, pyrantel pamoate, levamisole and thiabendazole. AB - Oesophagostomum bifurcum has recently been recognized as a common parasite of man in northern Togo and in Ghana. In a preliminary trial several anthelmintics were evaluated in the treatment of mixed Oesophagostomum and hookworm infections. Diagnosis was based on faecal culture, since the eggs of Oesophagostomum and hookworm cannot be distinguished morphologically. Of the anthelmintics tested, albendazole was most effective against both parasites. Pyrantel pamoate, 2 x 10 mg/kg, was effective against Oesophagostomum but not against hookworm. The cure rates for both parasites were moderate with thiabendazole and poor with levamisole. PMID- 8465410 TI - Treatment failure of a single high dose of ivermectin for Mansonella perstans filariasis. AB - Infections with Mansonella perstans are common in certain parts of Africa and South America. There is no standard treatment at present. We evaluated the effect of a single high dose of ivermectin (600 micrograms/kg) on microfilaraemia in 7 consecutive patients. No decrease in microfilarial counts could be demonstrated after a follow-up period of 7-56 d. PMID- 8465411 TI - Induction and modulation of the immune response to Leishmania by Montenegro's skin test. AB - The intradermal inoculation in naive or in previously sensitized individuals of small amounts of Leishmania extract (Montenegro's skin test) induced or modulated, respectively, the immune response to Leishmania, as assessed by subsequent Montenegro's skin tests. These phenomena could hinder the interpretation of Montenegro's skin tests in a population already subjected to the test in the past and, in addition, could affect in an unknown way the development of mucosal lesions in people infected with L. braziliensis or L. amazonensis, since those lesions have been associated with hypersensitivity to Leishmania antigens. Anti-Leishmania antibody responses, assessed by enzyme linked immunosorbent assay, were not induced in naive individuals by Montenegro's skin tests, but tended to become more intense following these tests in previously sensitized individuals. PMID- 8465412 TI - HIV-Leishmania co-infections in Italy: serological data as an indication of the sequence of acquisition of the two infections. AB - Twenty-two sera from visceral leishmaniasis (VL) patients with human immunodeficiency virus (HIV) infection (50% with the acquired immune deficiency syndrome) were examined for anti-Leishmania immunoglobulin G (IgG) antibodies and compared with 35 sera from VL patients without HIV (controls). Significant titres of specific IgG were found in 81.8% of co-infections. However, while control sera showed a restricted range of anti-Leishmania IgG titres, sera from co-infection cases displayed a considerable degree of variability, both quantitative and qualitative. They were clearly divided into 2 groups: one (18 sera) showing a continuous grading from nil to mid-concentrations of specific antibodies, the other (3 sera) showing titres 30-fold higher than this range. Taking into account the major immunological abnormalities involving humoral response described in HIV patient, the 2 groups may reflect a different sequence of acquisition of the 2 infective agents; the former representing VL acquired after HIV infection, and the latter representing the contrary situation. PMID- 8465413 TI - Partial characterization of antigens in circulating immune complexes in cystic hydatid patients treated with albendazole. AB - Immune complexes were precipitated by 3% polyethylene glycol (PEG) from 4 sera from albendazole-treated hydatid patients from Uruguay, and together with sheep hydatid cyst fluid were analysed by ion-exchange fast protein liquid chromatography (FPLC). FPLC-eluted fractions of serum preparations and cyst fluid were tested in an enzyme-linked immunosorbent assay for the detection of specific Echinococcus granulosus antigens and also for presence of specific immunoglobulin (Ig) M and IgG in the serum samples. Two peaks (nos 13 and 25) were found to have antigenic activity. Antigens were identified in both serum and cyst fluid preparation (fraction 25) after sodium dodecyl sulphate-polyacrylamide gel electrophoresis immunoblotting analysis, with approximate molecular masses 50 kDa and 62 kDa. Specific IgM antibody was also detected in the same FPLC fraction (no. 25) of PEG-precipitated serum complexes. PMID- 8465414 TI - Rationale for OKT3 monoclonal antibody treatment in transplant patients. PMID- 8465415 TI - General aspects of cytokine-release syndrome: timing and incidence of symptoms. AB - OKT3 has become a commonly employed immunosuppressant for transplantation both as a prophylactic agent and as a means of reversing rejection. It was first thought to have few side effects associated with its use, but many findings have become recognized as manifestations of cytokine release. The severity of some CRS symptoms can be reduced by careful patient management. Strategies to moderate CRS show promise. The potential for use of nonactivating anti-CD3 antibodies may obviate the symptom complex entirely. PMID- 8465416 TI - Cardiopulmonary effects of OKT3: determinants of hypotension, pulmonary edema, and cardiac dysfunction. PMID- 8465417 TI - OKT3-induced cytokine-release syndrome: renal effects (cytokine nephropathy). PMID- 8465418 TI - Cytokine nephropathy during antilymphocyte therapy. PMID- 8465419 TI - Encephalopathy following the use of OKT3 in renal allograft transplantation. PMID- 8465420 TI - Cytokine-release syndrome: differences between high and low doses of OKT3. PMID- 8465421 TI - Procoagulant properties of OKT3 at the monocyte level: inhibition by pentoxifylline. PMID- 8465422 TI - Administration of OKT3 in the operating room. PMID- 8465423 TI - Safety of OKT3 use in the operating room. PMID- 8465424 TI - Prophylactic OKT3: practical considerations for the prevention of first-dose reactions. PMID- 8465425 TI - OKT3-induced cytokine-release syndrome: prevention effect of anti-tumor necrosis factor monoclonal antibody. PMID- 8465426 TI - Reduction of the initial febrile response to OKT3 with indomethacin. PMID- 8465427 TI - Interleukin-10 inhibits OKT3-induced cytokine release: in vitro comparison with pentoxifylline. PMID- 8465428 TI - Pentoxifylline reduces the first-dose reactions following OKT3. PMID- 8465429 TI - Cytokine-release syndrome: general risk-factor modification--preparation of high risk patients for use of OKT3. PMID- 8465430 TI - Humoral immune response against OKT3. PMID- 8465431 TI - Transmembrane signaling requirements of T cells. PMID- 8465432 TI - OKT3 antibody response study: comparative testing of human antimouse antibody. PMID- 8465433 TI - Antibody response to OKT3 and methods for monitoring. AB - Monitoring the antibody response to OKT3 is essential. Retreatment with OKT3 can be accomplished successfully in the great majority of patients. It is important to know the patient's peak antibody status before and during retreatment. Patients with no anti-OKT3 antibodies, or with low-titer (< or = 1:100) antibodies, especially if these do not include anti-idiotypic antibodies, have retreatment success similar to that of patients undergoing primary treatment with OKT3. In contrast, patients with high-titer (> or = 1:1000) antibodies should be treated with immunosuppression other than OKT3. Methods for monitoring the OKT3 antibody response have progressed, allowing one to estimate the titer and specificity (anti-idiotype and/or anti-isotype) in a timely fashion. Improvements still must be made in the area of standardization, so that results between various transplant centers can be more accurately compared. PMID- 8465434 TI - Consequences of anti-OKT3 antibody development: OKT3 reuse and long-term graft survival. PMID- 8465435 TI - Monitoring OKT3 treatment: pharmacodynamic and pharmacokinetic measures. PMID- 8465436 TI - Consensus statement regarding OKT3-induced cytokine-release syndrome and human antimouse antibodies. PMID- 8465437 TI - Clinical observations on bovine parasitic otitis in Tanzania. AB - Between January 1982 and December 1989 more than 5,000 clinical cases of bovine parasitic otitis were examined. Clinical signs were mild in early cases and were characterised by dullness, anorexia and occasional head shaking, but were severe in long standing cases where the major presenting clinical signs were dark brown aural discharges which soiled the hair below and in front of the ear, emaciation, central nervous signs, recumbency and death. PMID- 8465438 TI - An evaluation of strategic and short interval tick control in indigenous exotic and crossbred cattle. AB - The performance of Nguni, Bonsmara and Hereford oxen which were maintained free of ticks by short interval treatment with acaricide irrespective of tick load (tactical) was compared with similar groups which were treated for tick infestation only when the numbers of adult ticks on the cattle increased to moderately high proportions (strategic). Strategically treated Nguni oxen acquired a strong resistance against ticks and showed weight gains comparable with the tick free Nguni group. Weight gains in the Bonsmara group were higher in the strategically treated group suggesting a possible effect of the acaricide on the tick free group. Strategically treated Hereford oxen acquired heavy tick burdens and performed poorly compared with the tick free group. Practical approaches to strategic tick control under African conditions are discussed. PMID- 8465439 TI - Oral vaccination of chickens with the V4 strain of Newcastle disease virus. Cooked and raw white rice as a vehicle. AB - Uncooked white rice and cooked white rice were tested as vehicles for the V4 strain of oral Newcastle disease vaccine. The results of feeding experiments were evaluated by the measurement of haemagglutination inhibition antibodies against Newcastle disease virus. Little of the virus applied to uncooked white rice could be recovered, even immediately after mixing, whereas when the virus was applied to cooked white rice most of it could be recovered. In 4 separate experiments, chickens failed to respond serologically to vaccine supplied on uncooked white rice. In all of 4 experiments with cooked white rice, there were serological responses in vaccinated chickens, from 45% to 100% of the chickens developing titres sufficiently high to indicate protection against challenge with virulent virus. Development of haemagglutination inhibition antibodies in some control chickens indicated the ability of the vaccine virus for lateral spread or persistence in the environment. PMID- 8465441 TI - Preweaning growth performance of west African shorthorn cattle and their Jersey crossbreds in Ghana. AB - Calf records on 621 West African Shorthorn (WASH) and 3 grades of Jersey x WASH crossbreds were analysed for the effects of the level of Jersey breeding and other factors on birth weight, 205-day weaning weight and average daily gain (ADG). Crossbred calves were significantly (P < 0.01) heavier at birth than purebred WASH and birth weights increased with increasing level of Jersey breeding. No significant differences were established for 205-day weaning weight, however ADG declined with increasing level of Jersey breeding suggesting possible problems of adaptation for calves of over 75% Jersey breeding. Age of dam effect was significant and linear (P < 0.0001) for birth weight and significant and quadratic (P < 0.01) for weaning weight and ADG, with values increasing from 3 year old dams to a peak in 7 year old dams. PMID- 8465440 TI - Efficacy of closantel against fenbendazole and levamisole resistant Haemonchus contortus in small ruminants. AB - Sheep infected with a fenbendazole resistant strain of Haemonchus contortus and goats with a levamisole resistant strain of the same parasite were used to evaluate the anthelmintic efficacy of closantel. Closantel at the rate of 10 mg/kg body weight was 100% effective against the 2 resistant strains of the parasite as indicated by faecal egg count and worm reduction. The efficacy of fenbendazole in sheep and of levamisole in goats was 56.68 and 76.90%, respectively. PMID- 8465442 TI - Grass hay and Acacia fruits: a local feeding system for improved calf performance in semi-arid Ethiopia. AB - A 90-day growth trial was designed to compare the performance of calves on 3 dry season diets composed of local resources from the Borana pastoral system. The control group received the traditional diet of cut-and-carry, standing-brown grass while the other diets consisted of grass hay stored since the previous wet season with or without Acacia tortilis fruits as a protein supplement. All calves had access to water once every 3 days as traditional. The objective was to see whether modest changes in traditional feeding management could enhance nutrient intake and growth of calves under conditions of restricted water access. The hay had a higher nitrogen content and in vitro digestibility than the standing grass, and the Acacia fruits had higher nutrient concentrations than the hay (both at P < or = 0.05). Calves on hay plus Acacia fruits had higher nitrogen intakes than those on hay only, and those on hay only had higher nitrogen intakes than those on standing grass (both at P < or = 0.05). Calves on standing grass lost weight and condition, those on hay only maintained weight but lost condition, and those on hay plus Acacia fruits gained weight and maintained condition (all at P < or = 0.05). Calves consumed the most feed on day 2 of the watering cycle, regardless of treatment. Water intake increased 27% for animals on both hay diets compared to those on standing grass (P < or = 0.01). Feeding packages based on hay making and collection of browse legumes are appropriate options for extension to these semi-settled pastoralists. PMID- 8465443 TI - Effect of change in body weight and condition during the dry season on capacity for work of draft oxen. AB - Work oxen supplemented at different levels during a feeding period of 3 months, were divided into 3 groups of average weight change -25, +35 and +70 kg and worked under loadings of either 7.5 or 12.5 kgf/100 kg of liveweight for 2 weeks, in order to assess the impact of dry season supplementation on capacity for work. At approximately equal levels of stress in work, manifest in maximum heart rate one minute after ceasing work (MHR), oxen with higher dry-season weight gain produced higher levels of work output, in proportion to their increased body weight. Rate of work and mean daily work output increased from the first to the second week of work, in spite of average daily weight losses of 2.63 kg throughout the period. Decline in rate of working through each day was continuous and essentially linear with relation to distance worked. The time taken to cover 1 km increased at an average of 0.16 and 0.68 min/km for light and heavy loadings respectively. Although MHR appeared to provide a retrospective measure of the level of stress attained in work, it was of limited use as a predictor of reasonable work demand. Maximum heart rate was related to work output (MJ) and animal liveweight (kg), as follows: MHR = 17.7 (+/- 3.94) WO - 0.15 (+/- 0.080) LWT + 118.5 (r2 = 0.70 P < 0.01). PMID- 8465444 TI - [Surgery of acoustic neurinoma--a national function]. PMID- 8465445 TI - [Acoustic neurinomas in Denmark. Incidence and therapeutic strategies]. AB - The annual incidence of diagnosed acoustic neurinomas in Denmark during two 7 year-periods from mid 1976 to mid 1990 is compared. Data on all patients operated via the translabyrinthine, transtemporal and suboccipital approach, as well as data on non-operated patients, was collected from the entire country. During the first period, from June 1976 to June 1983, the incidence was 7.8 tumors per million per year. During the second period, from June 1983 to June 1990, the annual incidence rose to 9.4 tumors per million per year. The number of newly diagnosed small tumors increased, and that of large tumors decreased. A significant increase was observed in Copenhagen. An incidence of 11 to 12 tumors per million per year, or nearly 60 newly-diagnosed tumors per year is thus expected around the year 2000. This limited number supports the continuation of the present centralized model of acoustic neurinoma surgery in Denmark. PMID- 8465446 TI - [Acoustic neurinoma: observation prior to surgery]. AB - During the period from 1977 to 1989 (both years included) 79 acoustic neurinomata were diagnosed in 76 patients in the County of Arhus. Twenty-four of these neurinomata were followed for varying periods clinically and radiographically. The symptoms of the patients and the results of successive computed-tomographic scans are mentioned. During the periods of observation, four patients were submitted to operation and operation was recommended in two cases. Seventeen patients are still under observation and are in good clinical condition with cessation or limited growth of the tumour in eight. These patients have been observed for between 1 and 13 years, on an average 4.5 years and are characterised by advanced age which averaged 61 years at the time of the diagnosis. The rate of growth of the tumour was calculated to be 1.1 mm per annum on an average with a variation from 0 mm to 4.8 mm per annum. As operative treatment of acouistic neurinoma exposes the patient to a not inconsiderable risk of deterioration the medical and/or socioeconomic status, the authors consider that an expectant and controlled attitude (wait and scan) is justified in elderly patients with acoustic neurinoma. PMID- 8465447 TI - [Results of suboccipital removal of acoustic neurinomas in Denmark 1979-1990]. AB - In the period from 1979 to 1990, a series of 59 patients with 59 acoustic neuromas were operated upon in five departments of neurosurgery by at least five different neurosurgical teams, employing the suboccipital approach. The perioperative mortality rate was 8.5%. Complications including hematoma, ventricular hemorrhage, meningitis, hemiparalysis, abducens nerve paralysis, recurrent nerve paralysis, postoperative wound infection and CSF leak were observed in 21 patients (35.6%). Radical removal of the tumor was not possible in 17 patients (28.8%). Converting the postoperative facial nerve function to the House-Brackmann (HB) classification, 34 patients (57.6%) were regarded as HB VI. Reconstruction of the facial nerve was attempted in 19 patients (32.2%). Attempts at preservation of hearing were unsuccessful in all patients. Failure to attain better results and the importance of the centralized Danish model of acoustic neuroma surgery are emphasized. PMID- 8465448 TI - [Lewy-body dementia--a new disease entity]. AB - Senile dementia of Lewy-body type (SDLB) is a new clinical entity characterized by mild extrapyramidal features and progressive dementia, a relative acute onset of fluctuating loss of memory and confusion, frequently accompanied by visual hallucinations. The syndrome is more frequently identified in women than in men and it occurs after the age of 60 years. A case history is presented and the diagnosis discussed on the basis of literature concerning Lewy-body dementia (LBD). PMID- 8465449 TI - [Magnesium therapy in pregnancy-induced hypertension and pre-eclampsia]. AB - At present, magnesium treatment is employed routinely in the treatment of hypertension induced by pregnancy (PIH) and preeclampsia in USA with the object of preventing seizures. In USA the treatment of election consists of intravenous infusion of large doses of magnesium sulphate in order to obtain a therapeutic concentration. The anticonvulsive mode of action of magnesium is only partially understood. Magnesium is presumed to block the neuromuscular transmission but a central effect cannot be excluded. Treatment with magnesium has, in addition, an antihypertensive effect. The effect of magnesium on the blood pressure is probably a direct vasodilatory effect which explains the ability of magnesium to reduce the maternal blood pressure. Probably the same mode of action is responsible for the relaxing effect of magnesium on the vascular tone in the umbilical and placental vessels. This can probably explain the favourable effect of magnesium on the birth weight. Even if magnesium treatment implies a potential risk for neonatal hypermagnesemia and hypocalcaemia, only few side effects have been reported. PMID- 8465450 TI - [Effect of pneumatic compression in connection with ergotherapeutic treatment of Colles' fracture. A clinical controlled trial]. AB - We followed forty women with functional deficits in the wrist and hand after sustaining a Colles' fracture. The women participated in occupational therapy three times a week for three weeks. At the initial evaluation, after three weeks, and at a three month evaluation, we measured the following: range of joint movement, grip strength, hand volume (oedema), pain and ADL. There was significant improvement in most of the parameters measured after three weeks of occupational therapy, with a less significant improvement from three weeks to three months. Seventeen of the forty women received twenty minutes of intermittent pneumatic compression before occupational therapy. These patients showed significant improvement in wrist extension, compared with the control group of twenty-three patients. Occupational therapy is recommended for patients showing a functional deficit after Colles' fracture. Intermittent pneumatic compression is recommended as a supplement to occupational therapy. PMID- 8465451 TI - [24 G Sprotte spinal cannula for anesthesia in young patients]. AB - We studied 75 patients aged 15-40 years who received spinal anaesthesia with the Sprotte 24-gauge spinal needle. The incidence of post dural puncture headache was 4%. Other types of headache occurred in 8% of the patients. The patient acceptance was high. We conclude that spinal anaesthesia is easy to perform with a 24-gauge Sprotte needle and is associated with a low incidence of post dural puncture headache. PMID- 8465452 TI - [Spinal analgesia in young patients using the Whitacre needle G25]. AB - A material of 100 patients aged 20-50 years was assessed after spinal analgesia with the Whitacre cannula G 25. None of the patients developed post-dural puncture headache. PMID- 8465454 TI - [Total serum cholesterol in postmenopausal women: prediction of future levels through a simple measurement]. PMID- 8465453 TI - [Serology in patients with scleroderma]. AB - In order to evaluate the practical clinical value of centromere, Scl-70, and nucleolar antibodies as demonstrated routinely by the Autoimmune Department of the Serum Institute of Copenhagen, 1293 sera from 497 patients with scleroderma (SSc) and other connective tissue diseases were tested for the three antibodies and for other nuclear antibodies. The three antibodies were found in 32, 15 and 15%, respectively, of sera from patients with SSc. Since more than one of the three antibodies was rarely demonstrated in any one serum, one of them was found in two thirds of sera from patients with SSc. The specificity of the three antibodies for SSc was 95% or more. Centromere antibody was found most frequently in patients with limited SSc. Scl-70 antibody was found almost exclusively in sera from patients with extensive SSc (involving the skin of the trunk). In such sera, centromere antibody was found in only 21%. Scl-70 antibody was overrepresented and centromere antibody was underrepresented in sera from patients with pulmonary involvement, the converse being true for sera from patients with calcinosis, esophageal involvement and telangiectasia. PMID- 8465455 TI - [Age at menarche among schoolgirls in Odense. Is age at menarche still decreasing in Denmark?]. AB - The average age at the menarche has decreased from the 1850s to the 1950s. It is controversial whether there has been a continued decrease since the 1950s. The object of this investigation is to illustrate whether this trend has continued into the 1980s. This study is based on the ages at the menarche as recalled by 908 girls aged 14-16 years in 40 schools in Odense. The information was obtained during intervals of differing lengths and consequently, the parameters of the distribution of the age at the menarche were estimated in a randomly grouped normal distribution. The average age at the menarche was found to be the same throughout the municipality (13.27 years; 95% confidence limit 13.20-13.35). The variations were found to be significantly differentiated by the type of school district. The variations were low in the suburbs and in the surrounding rural districts, higher in the inner city areas and highest among girls attending private schools. Compared with the results from other recent Danish studies, these findings suggest a halt in the decline of the average age at the menarche, which may be temporary. PMID- 8465456 TI - [Electrocoagulation of the endometrium. A new method for the treatment of hemorrhagic disorders in women]. AB - The purpose of this investigation was to evaluate endometrial ablation as an alternative treatment for heavy dysfunctional menstrual bleeding in women with indications for hysterectomy. After preliminary treatment with danazol 200 mg q.i.d. for four weeks, transcervical endometrial ablation was performed in general anaesthesia with a hysteroresectoscope and the "rollerball" electrode. Twenty-five consecutive patients were treated and discharged the following day. Twenty-two patients (88%) were very satisfied with the result. 68% became hypomenorrhoeic and 20% amenorrhoeic. Three patients required a hysterectomy because of continuing bleeding due to intrauterine septum and fibroma. The median follow-up time was seven months. Eight patients (32%) had either a submucus fibroid or an intrauterine septum. Neither uterine perforations nor major complications occurred. Endometrial ablation with the "rollerball" method appears to be an easy, cost-effective, safe and efficient treatment for heavy severe menorrhagia. PMID- 8465457 TI - [Treatment with ACE inhibitors after acute myocardial infarction]. PMID- 8465458 TI - [Smoking and involuntary sterility]. PMID- 8465459 TI - [Castration per occasionem]. PMID- 8465460 TI - [Castration of women as prevention against cancer]. PMID- 8465461 TI - [Transportation of critically ill patients]. PMID- 8465462 TI - [Osteoinduction with the dog tibial defect model]. AB - The objectives of this study were to investigate the osteoinductive effect of demineralized bone matrix powder and of cancellous bone in a comparative experiment in a standardized dog defect model. 16 adult shepard dogs were divided into two test subgroups. One group underwent application of demineralized bone matrix (DBM) into the defect. The second group had their defects treated with autogenous cancellous bone (ACG) only. The progress of bone formation was observed for twelve weeks. The excised tibiae were examined by correlating serial X-rays with histologic sections stained with Giemsa and fluorescent labels. In this experiment no osteoinductive effect of demineralized bone powder could be demonstrated. The amount and localisation of bone regeneration in the matrix group seemed to be spontaneous, corresponding to the radiological and histological parameters. In the group of cancellous bone grafts, the defect (length 30 mm) was bridged by incorporation of the graft and graft mediated bone formation within twelve weeks. Disturbing factors such as instability, infection, insufficient vascularity, and cellular immune response to the graft were excluded in this model. The failure of the osteoinductive implants in our experiment compared with the good results obtained in rodents limits their value also in clinical situations. As long as there is no explanation for this failure, this technique should not be used in a clinical situation. PMID- 8465463 TI - [Dynamic force measurement in implantation of total endoprostheses of the hip joint]. AB - The forces within the femoral shaft have been studied in preparation for the total hip replacement. The experimental device consisted of a personal computer connected with a digital enhanced measurement system which converted the data, that was received from the strain gauges, mounted on the femur. The bitochanter hip replacement designed by Ecke was used as an example of a press fit endoprosthesis which is anchored cementless. It was implanted in femora of cadavers. The results showed an extension of the femur at first within the intertrochanteric region, and as the rasp was further implanted, it showed at the distal end of the rasp a medial extension and a lateral traction with a delay of 3 ms, proving that it was a result of a medullary extension. The maximum forces applied with the metal hammer were 3500 N. Fractures and fissures were provoked and the result showed that they were mostly due to a misplacement of the rasp. PMID- 8465464 TI - [CORSET, experience with a new method of graft saving tissue replacement in large soft tissue defects]. AB - Following the proposal of Oedekoven we investigated the method of continuous and rapid skin enlargement by dynamic traction (which we named the CORSET-method) at the border of wounds, applied through elastic silicon rubber bands. Since March 1992 we operated more than 20 patients. By means of the "rubber bands" mentioned above soft tissues can be stimulated to grow, that is to say increase the area of skin that had to be treated with transplants priorily in order to close soft tissue defects following a compartment-syndrome or septic complications in the abdomic wall following operations in the abdomen. Applying the CORSET-method there is no risk of inflammation or soft tissue damage caused by the operation itself. PMID- 8465465 TI - [American football in Germany--aspects of trauma surgery]. AB - While football injuries in the USA are well documented and thoroughly studied, informations on injuries caused by this spreading sport in Germany are not available. For this reason the Berufsgenossenschaftliche Unfallklinik in Frankfurt conducted a prospective study to register all injuries in major league football in southern Germany in 1991. In 49 games that were evaluated we found 281 minor injuries, mainly skin lesions and concussions of extremities. In addition 33 significant injuries were registered, amongst them 30% injuries of knee ligaments. The only severe injury was an abdominal hit causing a intrahepatic hematoma. The results of our study are comparable to the injury risks found in US college football as well as to those found in German statistics on soccer and hockey. Although no fatal injuries in our study were registered, this should not lead to neglecting the potential risks in football. PMID- 8465466 TI - [Management of acromioclavicular joint dislocation with the Wolter hook-plate. One year follow-up of 35 cases]. AB - Wolter's hook-plate provides active abduction and forward-flexion of up to 90 degrees two days postoperatively. Prebending of the plate and a precise drill hole for the hook in the acromion prevents later impingement of the hook on the humeral head or subluxation in the acromioclavicular joint, respectively. According to the shoulder evaluation form of C.R. Constant, 33 of 35 patients operated on between 1987 and 1991 at the trauma departments in Schwaz/Tirol and Bad Ischl showed excellent results one year postoperatively. PMID- 8465467 TI - [Indications, technique and results in treatment of the chronically unstable ankle joint]. AB - This paper shall prove that with the chronic unstable ankle-joint the unit of both joints is to be taken into account. This unit consists anatomically as well as biomechanically and neuromuscularly. The practicable diagnostic of the instability in the lower ankle-joint ist presented. Then the known therapy methods are analysed. In our clinic some treatment methods for the single decompensate instabilities have proved success. The results of 119 operated decompensate ankle-joints are satisfied. PMID- 8465468 TI - [Anatomic studies of percutaneous bore wire osteosynthesis of the distal radius]. AB - Modified percutaneous K-wire pinning has been used for unstable distal radius fractures groups A 2.2-3, A 3.1-3, B 1.1-2, B 2.1-2, B 3.3, C 1.1-3, C 2.1-3, and C 3.1-2 according to the ASIF-classification in 90 patients with good results. No tendinous rupture or any weakness respectively, infection or secondary dislocation either had occurred six months postoperatively. In five cadavers experimental anatomical studies had revealed possible lesions of the tendons of the brachioradialis muscle, the short and long wrist extensors, the long thumb abductor and his short extensor respectively as well as the superficial radial nerve and the cephalic vein. Abnormous sensations in the scar or in the region of distribution of the superficial radial nerve had occurred in every second patient but had subsided six months postoperatively. No permanent nerve lesion was found. There has been bleeding from the cephalic vein after the stab incision for exposure of the tip of the styloid process in every third patient but had healed uneventfully in every case. PMID- 8465469 TI - [Development of statutory accident insurance in the new German districts from the medical viewpoint]. AB - In the five eastern federal districts of Germany the condition for organizing treatment forms of the Social Insurance for Occupational Accidents were different. In 1990 qualification of traumatologic surgeons demonstrated intensive standards and similarly positions as western Germany. On the other hand we have miserable buildings for patients and poor equipment. After two years the development of statutory accident insurance is respectable. The present situation reflects very good co-operation between western and eastern institutions, to remove some insufficiencies and to establish a sure territorial system for medical treatment. PMID- 8465470 TI - [A case of hyponatremia]. PMID- 8465471 TI - [Genetics in medicine: the 5th decade in Quebec]. PMID- 8465472 TI - [The diagnosis of mental retardation in fragile X syndrome is revolutionized by molecular genetics]. AB - The fragile X syndrome is the most common cause of inherited mental retardation. Clinical signs, which are neither specific to the syndrome nor constant, become apparent late in childhood or after puberty, making early diagnosis difficult on a clinical basis alone. The inheritance of the syndrome is peculiar for an X linked disease, since a high proportion of female carriers show a certain degree of mental retardation and "normal transmitting males" do exist. Affected males can be diagnosed by cytogenetic demonstration of the typical fragile X site but only a minority of female carriers can be identified. This makes genetic counseling difficult. In 1991, the cloning and sequencing of the target site of the mutation marked an important step towards full understanding of the peculiarities of inheritance of the fragile X syndrome. A new type of mutation has been revealed: a multistep "expansion" of a small part of a gene that takes place over several generations. A new diagnostic technique by direct genotypic analysis has been developed. With a very high sensitivity and specificity, this analysis detects affected individuals with a "full mutation" (a large "expansion" associated with abnormal methylation of the surrounding region) and individuals with a "premutation" (smaller "expansion") who do not show mental retardation but are at risk of having affected children or grand children. With the direct DNA analysis at the fragile X locus, it is now possible to diagnose easily those children affected with the syndrome and to offer adequate genetic counseling and prenatal diagnosis to female carriers in affected families.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465473 TI - [The emergence of viruses resistant to antiviral agents: a new challenge]. AB - Recent use of antiviral drugs and the increase in the number of viral infections in immunocompromised hosts have led to the development of viral resistance. In this paper, the author reviews the antiviral drugs on the market, the antiviral susceptibility tests and presents a review of the literature concerning infections with resistant viruses. Acyclovir-resistant herpes simplex and varicella-zoster virus, ganciclovir-resistant cytomegalovirus and zidovudine resistant human immunodeficiency virus will be discussed. PMID- 8465474 TI - [A anatomo-clinical conference at the Hotel-Dieu Hospital in Montreal. A 56-year old women presenting with bicytopenia]. PMID- 8465475 TI - [From the molecule to the drug: innovation or distribution]. PMID- 8465476 TI - [Revised guidelines related to booster vaccines against hepatitis B. The National Conference Committee on Immunization]. PMID- 8465477 TI - [Tuberculosis: a new disease. An interview with Dr. Alix Adrien]. PMID- 8465478 TI - Influence of immunotherapy (IL2 + LAK + inhibition of prostaglandin synthesis) on peripheral blood immune parameters and in vitro cytokine production in metastatic renal cell carcinoma. AB - Previous results on the peripheral blood immune status of renal cell carcinoma had indicated immunosuppression in metastatic disease, possibly mediated by prostaglandin E2 (PGE2). In the present study the immunologic effects of inhibition of PG synthesis by piroxicam in combination with interleukin 2 (IL 2) + lymphokine-activated killer (LAK) cell therapy were tested by immunomonitoring. In addition to peripheral blood parameters (lymphocyte subpopulations, neopterin, beta 2-microglobulin, TNF, IL 1, IFN gamma) we recorded in vitro cellular activity by incubating the patients' peripheral blood mononuclear cells (PBMC) in media containing fetal calf serum (FCS) or autologous serum, and either IL 2 or buffer. After 24 h of incubation we measured PGE2 and cytokine levels in supernatants. Systemic application of IL 2 induced in vivo lymphocyte proliferation and clearly influenced the serum levels of neopterin, beta 2 microglobulin and TNF. There was minor affection of IFN gamma and none of IL 1. PBMC in vitro produced high amounts of PGE2, IL 1 and TNF pretherapeutically, during therapy in vitro synthesis of these parameters decreased. Consistent production of IFN gamma was detected in supernatants only when FCS and IL 2 were added to the medium. Lack of affection of IFN gamma production in the autologous system during therapy indicated impaired cellular activity, which could neither be improved by therapy of the patient using IL 2 nor by adding IL 2 to the culture medium. Immunosuppression seems to interfere in a complex way with immunotherapy. Therapeutical influence of immunosuppression based on the results of immunomonitoring, however, seems to be a promising strategy for improving the still limited clinical results of immunotherapy. PMID- 8465479 TI - Effects of thiols on prostaglandin synthesis in bovine bladder epithelium. AB - The regulation of prostaglandin (PG) synthesis was characterized in microsomes of bovine bladder epithelium. Coenzyme A (CoA) and its metabolite cysteamine drastically decreased total PG synthesis. Furthermore, CoA inhibited solubilized cyclooxygenase which was precipitated by anti-cyclooxygenase antibody. Reduced glutathione (GSH) slightly increased total PG production and changed the pattern of PG synthesis. Other thiols, cysteine and ergothioneine, did not change total PG production. None of the thiols stimulated the incorporation of arachidonic acid into the phospholipid fraction. These findings suggest that CoA may directly regulate cyclooxygenase activity and GSH may subsequently change the pattern of PG production in bovine bladder epithelium. PMID- 8465480 TI - Intra- and perivesical tumor growth in preoperative staging of bladder cancer: the role of transrectal ultrasonography and high resolution magnetic resonance imaging. AB - Bladder tumors were staged preoperatively before and/or after M-VEC poly chemotherapy using transrectal ultrasonography and magnetic resonance imaging in 46 patients. The resultant findings were each compared with histomorphologic results. The sensitivity of both methods compared with pathohistology was 88%. Using this technique, the degree of tumor invasion of the bladder wall could be evaluated and the appropriate therapy selected. Further applications included the monitoring of transurethral resection determine its adequacy as a treatment modality. PMID- 8465481 TI - Quantification of prostaglandin E1 receptors in cavernous tissue of men, monkeys and dogs. AB - Prostaglandin E1 (PGE1) has been shown to relax the muscles of the corpora cavernosa and inhibit spontaneous activity, and clinical trials have proved its safety and effectiveness when given intracavernously to induce erection. Through use of a specific PGE1 receptor binding assay, we undertook this study to quantify its receptor density and measure binding affinity. The cavernous tissue of normal and impotent men as well as that of monkeys and dogs was studied in an attempt to understand their different responses to the intracavernous injection of PGE1. Our results showed a lower receptor density in impotent men than in normal men and monkeys and a complete absence of receptors in dogs. These findings correlated well with the clinical response to intracavernous injection of PGE1. PMID- 8465482 TI - Spontaneous passage of upper urinary tract calculi in relation to composition. AB - The composition of 2,755 calculi obtained from the upper urinary tract (1,409 by spontaneous passage and 1,346 by urological procedures) was analyzed using an infrared spectrophotometer, and the spontaneous passage rate was investigated in relation to the composition as well as other variables, such as stone size, and patient age and sex. Mixed stones of calcium oxalate and calcium phosphate were most frequently found, followed by those of calcium oxalate. The mean size (the maximum diameter) was largest in struvite stones and smallest in calcium oxalate ones. The sizes of stones from women were significantly larger than those from men (p < 0.01). As expected, the stone passage rates were inversely related to increasing stone size. The size of 55.6% of the stones passed was < or = 5 mm, and that of 96.6% of the stones < or = 10 mm. PMID- 8465483 TI - Studies on changes in parameters of the coagulation and fibrinolysis in association with extracorporeal shock wave lithotripsy. AB - Tissue damage by extracorporeal shock wave lithotripsy (ESWL) is assumed to be attributable to ischemic changes in the treated region surrounding the particular vessel which is first ruptured by shock waves. Such changes cannot take place without being accompanied by acceleration of coagulation and fibrinolysis. In the literature on renal damage by ESWL, no parameters of the coagulation and fibrinolysis of blood were used. The present study was designed to investigate renal damage by shock waves through the quantification of sequential changes in the following parameters between before and after ESWL: thrombin antithrombin III complex (TAT), alpha 2-plasmin inhibitor-plasmin complex (PIC), fibrin and fibrinogen degradation products (FDP) and D-dimer (D-D). In ESWL for renal stones, a significant acceleration of TAT occurred on the 1st postoperative day, followed by acceleration of PIC on the 3rd postoperative day. A transient acceleration was observed for FDP and D-D after operation. The levels of these parameters, however, returned to normal by the 1st postoperative week. In ESWL for ureteral stones, unlike for renal stones, none of the parameters showed statistically significant acceleration. In the construction of percutaneous nephrostomy (PNS) cases for ureteral stones before ESWL, none of the parameters showed significant acceleration either. Changes in these parameters of coagulation and fibrinolysis due to ESWL for renal stones were greater than those of construction of PNS or ESWL for ureteral stones. The reason for the difference of the alteration in these parameters between renal stones and ureteral stones were more abundant vessels in the kidney than the ureter. All these changes in the parameters, however, disappeared within almost 1 week. PMID- 8465484 TI - Calculus disease in duplex system--role of extracorporeal shockwave lithotripsy. AB - We report 8 patients with urolithiasis in a duplex system. These patients (7 males and 1 female) underwent 16 extracorporeal shock wave lithotripsy (ESWL) treatments. Five had renal and 3 had ureteral stones. The mean stone size was 21 mm (12-54 mm). Five patients had incomplete and 3 had complete duplication, of which one had an associated horseshoe kidney. Retrograde ureteropyelography was done in all the patients and in 7 a JJ stent was inserted. The JJ stent could not be inserted in 1 patient with incomplete duplication and retrograde catheterization with saline infusion was used as an auxiliary procedure. One patient with complete duplication had stones in both the ipsilateral ureters with a stone bulk of 54 mm and required two JJ stents. Only 1 paediatric patient required general anaesthesia. The 3-month stone-free rate was 100%. PMID- 8465485 TI - Splenic gonadal fusion with persistent mullerian duct syndrome. AB - Splenic gonadal fusion is a rare anomaly that is frequently associated with skeletal abnormalities or occasionally with cryptorchism. But the case of this anomaly accompanied by male pseudohermaphroditism here represents, to our knowledge, the first report of splenic gonadal fusion with persistent mullerian duct syndrome. PMID- 8465486 TI - Three cases with different types of short-tailed spermatozoa. AB - Short-tailed spermatozoa were found in 3 men attending our subfertility clinic. Light microscopy revealed basically normal sperm heads, but a short tail was found in 90% or more of the spermatozoa. Scanning and transmission electron microscopic examinations of the ejaculate revealed several types of short-tailed spermatozoa. In one case, the majority of the spermatozoa had a short, thick tail. In another case, all the spermatozoa were short-tailed, although two different types could be distinguished. As in the first case some spermatozoa were short- and thick-tailed, whereas others possessed an incomplete neck and middle piece, and a short, thick principal piece. In the third case, an elongated middle piece and short principal piece were found in almost all the short-tailed spermatozoa. Our electron-microscopic study revealed that the type of short tailed spermatozoa was different in each patient. PMID- 8465487 TI - Membranous lipodystrophy (Nasu's disease): a rare cause of neuropathic urinary incontinence. AB - A 37-year-old man with membranous lipodystrophy (Nasu's disease) was urodynamically studied, to elucidate his urinary incontinence. Although medication failed to improve this unfavorable condition, urodynamic assessment of this patient clearly demonstrated the existence of an uninhibited overactive bladder. PMID- 8465488 TI - Zoon's balanitis. AB - Superficial lesions of the glans penis can cause diagnostic difficulties. Zoon's balanitis can be distinguished by characteristic histological changes affecting the epidermis and the dermal vasculature. A 44-year-old male presented after having blood-staining of his underclothes for 5 months. Upon examination, the glans showed a red, moist plaque. Circumcision was performed, and the biopsy showed plasma cell balanitis. Following circumcision, the lesion healed completely. PMID- 8465489 TI - Principles of conventional radiography and fluoroscopy. AB - Diagnostic radiology is an extremely valuable tool in the practice of veterinary medicine. Basic knowledge of primary exposure factors and their interrelationship are required to consistently produce quality radiographs. This article discusses basic radiation physics and radiation safety guidelines. PMID- 8465490 TI - Radiographic positioning for the spine and skull. AB - This article presents an overview of the basic techniques for taking radiographs of the canine and feline spinal column and cranium. Radiographic landmarks, central ray positioning, centimeter measurement, and restrictive beam uses are discussed. PMID- 8465491 TI - Contrast agents. AB - Pharmacologic development and clinical use of nonionic low osmolality contrast agents have lowered incidences of contrast reactions. Exclusive use of these agents may be limited owing to their high costs. Ionic high osmolality agents still provide reliable means of positive contrast enhancement, and minimal problems with reactions have been experienced in veterinary patients. PMID- 8465492 TI - Contrast studies of the urogenital system. AB - Traditional contrast radiographic techniques for evaluation of the urogenital system are reviewed. Specific procedural protocols are suggested. The indications, limitations, and interpretation of the studies are discussed. PMID- 8465493 TI - Myelography and epidurography. AB - To summarize the points discussed in this article, Small animal myelography can be performed competently and safely without specialized equipment. The newer myelographic contrast media (iohexol, iopamidol) have less neurotoxic potential than those media previously used. Myelography is necessary for the diagnosis of many neurologic disorders in small animals. Metrizamide is no longer recommended for myelography in dogs and cats. Iohexol (Isovue) in concentration of 180 mg I/mL to 300 mg I/mL is recommended for small animal myelography. Some patients with serious spinal cord disease can exhibit normal myelograms. Recognizing abnormal myelographic patterns is the hallmark of myelographic interpretation. Anticonvulsive drugs (diazepam, pentobarbital, and phenobarbital) should be available for therapy of postmyelographic seizures. Epidurography is an effective diagnostic technique in the evaluation of canine lumbosacral compressive disease. Abnormalities identified with epidurography correlate well with surgically confirmed lesions. PMID- 8465494 TI - Selected contrast studies. Portal venography and cerebral angiography. AB - Portography is the most commonly used technique for demonstrating portal venous anatomy and abnormal communications between the portal and systemic venous systems. This article reviews normal anatomy, anomalies, and radiology of the portal venous system. Also included is a discussion of cerebral angiography, which is mainly used in the diagnosis of space-occupying lesions of the brain. PMID- 8465495 TI - Ultrasonography. AB - The basic principles of diagnostic ultrasonography are discussed. Normal and abnormal ultrasonographic appearances of the major organs are presented in tables and with illustrations. A description of the current status of neurosonology with illustrations of hydrocephalus is also presented. PMID- 8465496 TI - Nuclear imaging. AB - Nuclear imaging (scintigraphy) is a noninvasive diagnostic procedure that can provide complementary information to that obtained by radiography, CT, MRI, or ultrasonography. Nuclear imaging is based on physiologic distribution of radiopharmaceutical compounds within the body so that it allows assessment of organ functions. When digital image processing is employed, nuclear imaging can allow quantitative assessment of organ function. This article provides an overview of common nuclear imaging procedures used in veterinary medicine. PMID- 8465497 TI - Principles and concepts of computed tomography. AB - The final CT image is actually made of a grid of tiny squares called pixels. The scale of grays assigned to each pixel represents the attenuation of x-rays by the structures in the tomographic slice. Manipulation of the gray scale allows optimal visualization of all the tissues within the slice. This control over the gray scale and the absence of structure superimposition are the advantages of CT over conventional x-ray techniques. The steps used to acquire the final CT image are collection of data from the patient (recording of transmitted x-ray intensities from many angles), computer processing of data (mathematical calculation of attenuation of each structure in the tomographic slice), image display (assigning of appropriate gray scale to CT image to evaluate all structures), and data storage (recording series of tomographic images on x-ray film and archiving image data for later review). Common image artifacts that must be identified and interpreted as such include aliasing, ring artifacts, beam hardening effect, metal, motion, partial volume averaging, and streaking from out of-field objects. PMID- 8465498 TI - Interpretation of computed tomographic images. AB - This article discusses the production of optimal CT images in small animal patients as well as principles of radiographic interpretation. Technical factors affecting image quality and aiding image interpretation are included. Specific considerations for scanning various anatomic areas are given, including indications and potential pitfalls. Principles of radiographic interpretation are discussed. Selected patient images are illustrated. PMID- 8465499 TI - Magnetic resonance imaging. AB - The advent of advanced imaging techniques in veterinary diagnostics has broadened the scope of our diagnostic capabilities. MRI is one of the newer advanced imaging techniques, and its characteristics differ considerably from CT or conventional radiography. This article presents an introduction to MRI and interpretation of MR images. PMID- 8465500 TI - New and future advanced imaging techniques. AB - The advances in diagnostic imaging in the past 20 years have been nothing short of phenomenal. This article presents what is available with some of the latest in state-of-the-art techniques. Included are three-dimensional techniques, vascular MRI, high-resolution three-dimensional video animation, positron emission tomography, MR spectroscopy, and other developing methodology in diagnostic imaging. PMID- 8465501 TI - Experimental transmission of an apparent viral pneumonia in conventional and gnotobiotic pigs. AB - Endemic pneumonia in five- to eight-week-old pigs induced microscopic lesions of proliferative interstitial pneumonia which were compatible with a viral aetiology. The disease was transmitted experimentally to conventional and gnotobiotic pigs by means of a lung homogenate filtered through a 0.22 micron filter. No common viral respiratory pathogens of pigs were isolated. Two types of virus particles were observed in cell culture by electron microscopy; one was about 70 nm in diameter and had an envelope and short surface spicules, the other also had an envelope, was elongated, pleomorphic, measured 80 x 320 nm and was coated by antibodies. PMID- 8465502 TI - Two fatal cases of diarrhoea in horses associated with larvae of the small strongyles. AB - Detailed pathological examinations of two horses with subacute fatal diarrhoea suggested an association between the diarrhoea and damage to the colonic and caecal mucosae caused by large numbers of cyathostome larvae (larval cyathostomiasis). The affected animals deteriorated rapidly, and died after a short illness. PMID- 8465503 TI - Renal dysplasia in two adult horses: clinical and pathological aspects. AB - Renal dysplasia is reported in two adult horses in chronic renal failure. Renal dysplasia, complicated by severe interstitial pyelonephritis, was diagnosed on renal biopsy and confirmed on post mortem examination. PMID- 8465504 TI - Effects of the accidental feeding of lasalocid sodium to broiler breeder chickens. AB - Lasalocid sodium was accidentally introduced into the feed of several broiler breeder chicken farms at levels between 115 and 150 ppm. On one farm, leg weakness and ataxia were observed in a few cockerels. A reduction in egg production and a sharp decrease in fertility and hatchability were observed in all the flocks receiving the contaminated feed. Many piping chicks were unable to hatch and there was an increase in the number of weak ataxic chicks at the hatchery. Histological examination of the muscle tissues of the affected cockerels, the piping chicks unable to hatch and the one-day-old chicks with leg weakness and ataxia revealed severe muscle damage. Increasing levels of lasalocid were detected in the yolk of eggs collected from the affected flocks. PMID- 8465505 TI - A paralytic-like disease of the ostrich (Struthio camelus masaicus) associated with Clostridium chauvoei infection. AB - Two adult Masai ostriches in a zoological collection became recumbent. The birds could not raise the neck or the head, had difficulties in breathing, and died eight and 13 days, respectively, after the first clinical signs appeared. On post mortem examination the heart had a globous appearance accompanied by gelatinous atrophy. The lungs were hyperaemic and oedematic, while the intestines had prominent haemorrhages in their mucosa. The liver and kidney were enlarged, and the former had also necrotic foci. Smears taken from the hyperaemic regions of the intestines and the necrotic foci of the liver were positive to Clostridium chauvoei after staining with specific fluorescein-labelled antiserum. No other pathogenic agents were identified or isolated from these birds. This report appears to be the first of a pathogenic condition associated with C chauvoei in an avian species. PMID- 8465506 TI - Foot-and-mouth disease in Italy. PMID- 8465507 TI - Qualifications in Europe. PMID- 8465508 TI - Meat hygiene service. PMID- 8465509 TI - Fatal BVDV infection in adult cattle. PMID- 8465510 TI - Streptococcus suis infection in fallow deer. PMID- 8465511 TI - Deworming of pigeons with Panacur capsules. PMID- 8465512 TI - Grain overload in two dogs. PMID- 8465513 TI - Immunohistochemical detection of the p53 oncoprotein in tumours of melanocytic origin. AB - We employed the polyclonal anti-p53 antibody NCL-CM1 to cultured cells and pathological tissues in order to investigate the expression of p53 oncoprotein in human malignant melanomas. The results in the cultured cells showed that the antigenic determinant was sensitive to formalin fixation, resulting in a lower reactivity than with fixation by alcohol. In pathological tissues, the expression of p53 oncoprotein increased with progression of the tumour. Among 79 melanomas 37 (47%) showed distinct nuclear labelling and the highest proportion of reactive cells was observed in metastatic melanomas (mean 4.8%). An immunocytochemical study also revealed the presence of mutant-type oncoprotein in human melanoma cell lines, which was recognized by monoclonal antibody P240, and we confirmed that the molecular weight of the antigens recognized by both antibodies was 53 kDa by Western blot analysis. Therefore, although the presence of point mutations in human melanomas is yet to be confirmed our data suggest that the antigen detected by NCL-CM1 is a mutant-type or a complex of mutant and wild-type p53 oncoproteins. This antibody may be useful in retrospective studies of tumours of melanocytic origin. PMID- 8465514 TI - Cellular and matrix changes in drug abuser liver sinusoids: a semiquantitative and morphometric ultrastructural study. AB - The aim of the present work was to analyse, at the ultrastructural level, the action of heroin of 150 centrilobular sinusoids from liver biopsies of five intravenous drug abusers, who presented clinical and biological manifestations of hepatic impairment. A comparative study of 90 sinusoids from liver biopsies of three control patients was performed. Electron microscopic observations showed a thickening of the sinusoidal wall related to endothelial cell hypertrophy and to fibrosis of the space of Disse. This was generally associated with basement membrane-like material and hepatocyte microvilli flattening. In addicts, hepatic vascular pole changes were a constant finding, accompanied by interhepatocyte space disjunction and perisinusoidal collagenization. Morphometric assessment confirmed a significant increase of sinusoidal wall surface, endothelial cell body and processes and Ito cell process surface was significantly different between the patient groups. This cellular hypertrophy may represent hyperactivation of the sinusoidal cell functional capacity, triggering the fibrogenesis in the space of Disse. While this mechanical barrier might hinder the free exchange through the space of Disse, it may equally well protect the liver against heroin toxicity. PMID- 8465515 TI - Role of the notochord in the development of cephalic structures in normal and anencephalic human fetuses. AB - Normal and anencephalic human conceptuses were analysed histologically to investigate the role of differentiation of the intracranial notochord and its relation to the formation of the basichondrocranium. We have examined 16 normal embryos and fetuses and 4 anencephalic fetuses. Each developmental stage of formation of the normal basichondrocranium presented specific morphological changes during the course of notochord depletion. In contrast with normal specimens, anencephalic fetuses presented malformations of the basichondrocranium which were always related to an abnormal position of the notochord. Macroscopical differences between craniorachischisis and cranioschisis in fetuses with anencephaly correlated with the existence of two histologically different degrees of malformation. In fetuses with craniorachischisis we found severe disturbances in the shape, position and ossification of the basichondrocranium and in the course of the intracranial notochord. In fetuses with cranioschisis the described disturbances of the basichondrocranium and intracranial notochord were mild. In addition, marked differences in affection of the central nervous system and the hypophysis were observed. These findings suggest different periods of dysmorphogenesis. Our results underline the importance of the chordal mesoderm in the differentiation for the formation of cephalic structures in Man. PMID- 8465516 TI - Thrombendarteriitis pulmonalis carcinomatosa Ceelen: an immunohistological investigation. AB - A 65-year-old woman died in sudden right heart failure caused by thrombendarteriitis pulmonalis carcinomatosa Ceelen 16 months after resection of a rectal carcinoma. Autopsy disclosed a complex picture of multiple tumour cell emboli in small pulmonary arteries associated with local thrombosis and thrombus associated vessel wall reaction. This was characterized by movement of medial muscle cells into the thrombus. In addition, affected vessels showed a prominent perivascular tumour-related infiltration by lymphocytes which are identified immunohistochemically as CD3-reactive T-cells. PMID- 8465517 TI - Notochordal alterations in axial skeletal-neural dysraphic disorders. PMID- 8465519 TI - [Acquired hyperostosis syndrome (so-called pustular arthro-osteitis). Review of the literature including 73 personal cases]. AB - The acquired hyperostosis syndrome (AHS) (best known synonym: pustulotic arthro osteitis) is a system disease of the supporting and gliding tissue with sites of predilection characterized by inflammation-induced bony reconstruction of positive balance. This syndrome is affiliated with the seronegative spondylarthropathies. The main finding is the sternocostoclavicular hyperostosis in about 80% of patients. Focal hyperostoses also occur on the skeleton of truncus and extremities and joints. AHS is accompanied by psoriasiform and acneform dermatoses. Overlapping findings with spondylitis ankylosans are reported. Terminology, aetiology, nosology, pathogenesis, histomorphology, clinical and laboratory findings, complications, imaging diagnostic, differential diagnosis and therapy of AHS are discussed. Knowing AHS helps to prevent misdiagnoses (as especially bacterial osteomyelitis, spondylitis, osteoplastic tumor and metastases) and interventional diagnostic procedures. PMID- 8465518 TI - Modulation of perisinusoidal cell cytoskeletal features during experimental hepatic fibrosis. AB - Hepatic perisinusoidal cells (PSCs) proliferate and are thought to be the principal source of extracellular matrix proteins during the development of liver fibrosis. We have studied the classical model of carbon tetrachloride induced liver fibrosis in order to evaluate the possible modulation of PSCs into a synthetically active and contractile cell: the myofibroblast (MF). At the ultrastructural level, this modulation was characterized by reduction of lipid vacuoles and appearance of a developed rough endoplasmic reticulum as well as of microfilament bundles. On investigating the cytoskeletal equipment of PSCs and MFs using light and electron microscopic immunohistochemistry, we found a heterogeneity of phenotypic features. While typical PSCs in normal and fibrotic livers always contained desmin, MFs expressed alpha-smooth muscle (SM) actin in areas of tissue injury and active fibrogenesis. Cells co-expressing alpha-SM actin and desmin were most prominent in the prevenular zone of the lobule (known to be vulnerable to carbon tetrachloride toxicity) and in developing fibrous septa. As demonstrated by immunogold electron microscopy, labelling of microfilament bundles by alpha-SM actin antibody was noted in PSCs containing lipid droplets in early stages of fibrosis; here MFs gradually accumulated and showed alpha-SM actin containing microfilament bundles. In scar tissue, alpha-SM actin expression decreased in both PSCs and myofibroblasts. Our observations support the concept of phenotypic plasticity of PSCs and confirm, at the ultrastructural level, previous suggestions of modulation of these cells into MFs in the course of liver fibrosis. PMID- 8465520 TI - [Aneurysma spurium after iatrogenic arterial puncture--incidence, risk factors and surgical therapy]. AB - Due to the markedly increased number of arterial punctures performed during diagnostic angiography and angioplasty procedures for cardiac and peripheral vessel disease, the complication of false aneurysms after arterial puncture has gained increasing significance. The incidence of false aneurysms after puncture reported in the literature ranges from 0.05-2%. However, careful sonographic follow-up may reveal an incidence twice as high. The goal of this retrospective investigation of 28 patients with false aneurysms was to elucidate risk factors leading to failure of spontaneous closure of the arterial site, as well as to examine the symptoms and clinical course of such patients. Pseudoaneurysms became manifest, depending on the method of puncture, on average 16.4 days after the procedure. The highest risk was seen in adipose patients (18 pts., 64.3%). In these patients the number of tangential and multiple vessel punctures was also highest. Further risk factors were local vessel sclerosis, hypertension, diabetes mellitus, poor general condition, and disturbances of blood coagulation. The typical clinical findings were seen in only 13 patients. In 3 patients blood loss was the predominant symptom. Twelve further pseudoaneurysms (42.8%) were found incidentally at follow-up. The diagnosis was made in all patients sonographically. In 1 patient it was initially identified as an incidental finding at angiography. In 25 cases simple vessel reconstruction was possible (stitch or patch). In 3 cases (10.7%) a more extensive procedure involving vessel replacement was necessary. Severe postoperative complications included local infection (in 2 patients, 1 of whom also had a recurrent false aneurysm) and arterial bleeding necessitating surgical intervention (1 patient).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465521 TI - [Retroperitoneal vascular injuries as a complication of lumbar disc operation]. AB - We describe 2 cases of retroperitoneal hematoma after lumbar disc surgery following injury to retroperitoneal vessels. One patient sustained a partial tear of the right common iliac artery during left L4/5 discectomy, the other a complete tear of the lowest lumbar artery during left L5/S1 discectomy. Both patients developed hypovolemic shock 4-5 hours postoperatively, with acute abdominal symptoms and signs; the former patient also showed signs of ischemia of the right lower extremity. Both recovered completely after surgical intervention with vascular repair and evacuation of the retroperitoneal hematoma. PMID- 8465522 TI - [Replacement of the anterior cruciate ligament with an artificial Leeds-Keio ligament]. PMID- 8465523 TI - [Percutaneous transluminal angioplasty of the carotid artery]. AB - This paper presents personal experience of 169 percutaneous transluminal angioplasties (PTA) and more than 1,000 worldwide published results of angioplasty on supraaortic stenoses especially of the carotid artery. The technique of the angioplastic procedure, essential pretherapeutic diagnostic methods and indications of PTA are described and discussed. Results of published and own experience indicate that PTA is an effective and alternative method to vascular surgery in the treatment of symptomatic carotid artery stenoses. With strict definition of the indication, the complication rate for PTA is not likely to be higher than that for vascular surgical treatment. PTA of carotid artery stenosis should be used exclusively in medical centers in which a cooperation by vascular surgeons, internists, neurologists and interventional radiologists or neuroradiologists comes true. PMID- 8465524 TI - [Stenosis of the extracranial carotid artery]. AB - Magnetic resonance angiography (MRA) as well as intraarterial digital subtraction angiography (DSA) were performed in 45 patients suffering from cerebrovascular disease, both procedures within one week of each other. MRA und DSA were evaluated separately for every patient retrospectively by two experienced radiologists on consensus basis. The results were then compared using catheter angiography as gold standard. Evaluation was confined to the common and internal carotid arteries (CCA, ICA) in the neck subdivided into 5 grades of stenosis. A comparative assessment was impossible in 9% cases due to motion artifacts and patient malposition. Out of 18 verified CCA stenoses 13 were demonstrated by MRA and 39 out of 44 ICA stenoses were assessed by MRA. There was a highly significant correlation between degree of stenosis detected by the two methods. Spearman Rank correlation coefficients of 0.824 and 0.913 were found for CCA and ICA, respectively. PMID- 8465525 TI - [Psychological aspects as predicting factors for the indication of acupuncture in migraine patients]. AB - 30 patients with chronic migraine received needle acupuncture after investigation of personality traits, cognitive and social factors. Treatment response was evaluated in two different ways (documentation of attacks in a migraine diary and subjective judgment of outcome). Diary documentation showed that the frequency of attacks was halved, with no essential relation to psychological factors. Short duration of illness was the best predictor of a good response to therapy. Patients' subjective judgement demonstrated a mean improvement of 60%. Unlike diary documentation, the subjective response rates were closely related to personality traits. In particular, patients with high scores for extroversion and low scores for neuroticism reported a better response. Age, sex, social status, and expectations of benefit did not show any relation to treatment efficacy. PMID- 8465526 TI - [Development and testing of a model for simultaneous evaluation of muscle relaxation on three intrinsic laryngeal muscles and on the anterior tibial muscle]. PMID- 8465527 TI - [Human dignity and Christian ethics]. AB - The jurisdiction of most states presumes that human dignity is unconditional. Yet a last reason for this dignity cannot be furnished by a state jurisdiction. Christian ethics for instance argue on a line beyond strictly rational interpretation: human dignity roots in man's affirmation by God. Beyond a simply negative definition it is essential today to define the conditions of human dignity in a positive way. PMID- 8465528 TI - [The concepts of "human dignity" and "sanctity of life" and their relations to ethical conflicts in modern medicine Bielefeld, 1 to 3 October 1992)]. PMID- 8465529 TI - [Holistic anthropology in oncology]. PMID- 8465530 TI - [Brief definitions of medical ethics concepts. 24. "Human dignity" in documents]. PMID- 8465531 TI - [Arterial vascular training]. AB - By means of a specific arterial vessel training--indoor or outdoor--it is in any case possible to improve the individual walking performance. In the first phase of the training there is an increase of the arterial maximal flow, which then remains constant and may even rapidly decline without further training. The continual increase can be explained through metabolic, hemorheologic, and possibly microcirculatoric changes (microbiopsy studies, not yet published). At the moment it is only Germany where you can find the complete offer of all different vessel training. In Austria there is only the indoor training which works at the moment. The different German health-insurance pay the training programs, the criteria for the education of "the vessel-trainer" are established by the health-insurance, by the "Deutsche Gesellschaft fur Angiologie" and the "Deutsche Gesellschaft fur Gefasssport (vessel training)". The vessel trainer has to achieve his diploma via the "A" and "coronar certificate". In Austria there are no obligatory criteria for this education--neither for the coronary nor for the vessel training--there is no observation of the education and no payment system. PMID- 8465532 TI - [Therapeutic training and sports in chronic diseases of the lung]. AB - Training is defined as systematic physical activity in order to improve the physical working capacity, which causes measurable morphological and functional changes in organs. Effects and the rules of applying aerobic endurance training in patients with chronic diseases of the lungs are dealt with. Training does not replace the normal medication, but is an additional therapeutic mean in order to regain physical working capacity, lost by chronic immobilization in the natural course of disease. Contraindications are acute diseases and exacerbations, but not a certain degree of the disease. Training does not improve the lung function, but the function of the other organs, the physical working capacity ist based on (circulation, musculature). This helps to use optimally the remaining reserves of lung function. Methods of aerobic endurance training are described, the definition of aims, performance diagnostic and the finding of the exact doses of training according to intensity, duration, frequency and the weekly netto training time. The training in different diseases of the lungs is discussed: In asthma bronchiale the prophylaxis of the exercise induced asthma and permitted and forbidden drugs for asthmatics according to the rules of international olympic committee. In chronic bronchitis with arterial hypoxemia, in restrictive lung diseases and in pulmonary hypertension. At last the way to prescribing training for patients with chronic pulmonary diseases is described as well as the advising of patients wishing to do sport by their own motivation or planning projects, for instance touristic ones, which require physical stress. PMID- 8465533 TI - [Ambulatory medical training therapy in coronary heart disease]. AB - Physical exercise plays a central role within cardiac rehabilitation. Most often, endurance exercises are restricted only to inpatient rehabilitation regimes. According to the guidelines of sports medicine, endurance training is only effective if it is performed regularly and systematically. With regards to safety and best control, bicycle ergometer is the training device of choice for the cardiac patient. Prescription and organisation of endurance training sessions in cardiac rehabilitation are discussed. Beside the well accepted changes of risk factors by regular endurance training, studies of pooled data showed a significant reduction of mortality of patients in the rehabilitation groups. The lack of data regarding training time and intensity within the single studies was remarkable. PMID- 8465534 TI - [The science of medical training]. AB - The medical science of training (MST) is the theoretical basis for a proper advice in problems of physical performance in healthy and people with chronic diseases. This is comparable with the pharmacology as a basis for the advice in internal medicine. The MST deals with the rules, which are valid for improving the physical performance by training, changing the morphology and function of organ systems. Basis of MST is the knowledge of the effects of each training measure and the knowledge of a relation between the doses and the effect of training. Out of 5 basic motoric properties, endurance, strength, coordination, flexibility and fastness, the MST deals with endurance and strength. These 2 basic motoric properties are determined by the morphology and function of organ systems and are changeable by training. Endurance is defined as the faculty of resynthesizing ATP which was consumed by muscular activity. According to the type of resynthesis two aerobic types, extensive aerobic endurance and intensive aerobic endurance, and 2 anaerobic types, lactacide anaerobic endurance and a lactacide anaerobic endurance can be distinguished. These 4 types of endurance are defined biochemically and the methods of training are described, proved and evaluated for use in preventive and therapeutic training. Strength is defined as the faculty of the muscle to produce tension. The methods of training are described, proved physiologically, and evaluated for use in preventive and therapeutic training. General and special rules for sport medical advice for people with enhanced health risk and or chronic diseases are presented. PMID- 8465535 TI - [Diabetes and sports]. AB - Through better understanding of the physiology of physical exercise in normal and diabetic subjects we can more closely define the significance of regular physical exercise in the treatment of diabetes. Although patients with type I and type II diabetes can obtain different advantages from regular physical exercise, this activity is in turn connected with different risks. The introduction of self monitoring of blood glucose has though considerably eased management in relation to physical activity by type I diabetics. Essentially the risk to type I diabetics is that of developing hypoglycemia during or after exercise as well as the danger of a worsening of metabolic levels with the development of ketoacidosis. In type II diabetics the risk of hypoglycemia is less pronounced and in patients treated solely by dietary means the regulation of blood glucose presents no great problem. With these individuals regular physical activity can be implemented as a further therapeutic tool towards the normalisation of body weight and an improvement in insulin sensitivity. With appropriate training and self-control the potential hypoglycemia in type I diabetic patients can easily be avoided. For this reason regular physical exercise can be recommended as a cornerstone of therapy, both in the management of type I as well as type II diabetes. The positive effect of exercise is significantly better defined in regard to type II diabetics than with type I diabetics. In particular, regular physical exercise can be implemented as a supplement to caloric restriction for weight reduction and as a means to improve insulin sensitivity in the obese insulin-resistant individual. PMID- 8465536 TI - Child alert 10-33. PMID- 8465537 TI - SMS reform plan needs revisions. PMID- 8465538 TI - Discuss WIPRO letters with patients. PMID- 8465539 TI - Short-term focused cognitive therapy of panic disorder with aerophobia: a case report. AB - The efficacy of focused cognitive therapy was evaluated in the short-term treatment of a flight instructor suffering from panic disorder with aerophobic and agoraphobic symptoms. A modified panic induction technique (hyperventilation) was used in session to activate the specific bodily sensations he typically experienced during panic attacks. The patient was then asked to articulate his catastrophic interpretations of the physiological sensations he was experiencing and taught to re-interpret them in a non-catastrophic manner, which enabled him to reduce his symptoms to a more manageable level. After four sessions of focused cognitive therapy, the patient's panic and phobic symptoms were significantly reduced and no longer interfered with his daily functioning. Posttreatment follow up at 6 and 9 months revealed that the patient was completely free of panic while flying. PMID- 8465540 TI - Munchausen's syndrome: the importance of a comprehensive medical history. AB - Munchausen's syndrome was first described by Asher in 1951. Then Ireland, et al, described eight criteria that characterized these patients. These characteristics include factitious illness of a dramatic nature, factitious evidence of disease, evidence of multiple medical procedures, pathologic lying, aggressive behavior, leaving the hospital against medical advice, multiple hospitalizations with traveling and absence of any obvious secondary gain. Another form of this disease is Munchausen's syndrome by proxy which describes parental behavior that creates the appearance of, or produces, physical illness in a child with harmful consequences to the child. In this report, we present a complex case of Munchausen's syndrome in a patient who has been traveling around the country, going from one hospital to another for several years. We ask physicians to be aware of the features of this patient, bearing in mind that this was her third hospitalization at the University of Wisconsin Hospital in Madison. PMID- 8465541 TI - Unusual scrotal mass in the neonate. AB - Ultrasound is an ideal imaging modality that may be used to evaluate scrotal masses. It will frequently detect the presence of a mass, localize its site of origin, and characterize the abnormality. The most valuable information provided by ultrasound is the separation of intra- and extratesticular lesions. The importance of this distinction is understood when it is recognized that the majority of intratesticular lesions are malignant, while more extratesticular lesions are benign. The accuracy in this determination is between 90% and 95%. The overall accuracy in detecting and characterizing soft tissue masses as cystic or solid is in the range of 90% to 100%. Once a solid mass is identified, it is not possible to distinguish benign from malignant. We present the ultrasound findings of a newborn with renal vein thrombosis and a left scrotal enlargement, and discuss its pathogenesis. PMID- 8465542 TI - Adult occupational lead exposure in Wisconsin. PMID- 8465543 TI - Recent court ruling on blood alcohol testing has no effect on physician's role. PMID- 8465544 TI - Alternative dispute resolution of medical malpractice cases in Wisconsin. PMID- 8465545 TI - [Ulcerative colitis and Crohn disease from the immunologic viewpoint]. AB - A critical immunological survey is given on etiology and pathogenesis of ulcerative colitis and Crohn's disease. Since antigen specific suppressor cells are presumably not very likely, the appropriate hypotheses must be replaced by new ones. Assuming disturbances of the regulation of the immune system as the key to etiopathogenesis, a genetic hypothesis can be presented. This hypothesis is based on the assumption of physiological and pathogenic autogenes as well as regulator genes. PMID- 8465546 TI - [Possibilities and limits of medical graphology: determination of current status and perspectives (III)]. PMID- 8465547 TI - [Endoscopic ultrasound in TN staging of stomach cancer. A comparison with computerized tomography and conventional ultrasound]. AB - 64 patients with histologically proven gastric carcinoma were investigated by endosonography (EUS), computed tomography (CT) and conventional transcutaneous sonography (US). In 50 patients a resection of the stomach was performed and the histological findings were compared with the results of preoperative staging. In all cases EUS was successful in demonstrating the tumour. With CT tumour visualisation was possible in 17 (35.4%), with US in 7 (14.6%) cases. The pT stage was correctly determined preoperatively by EUS in 40 (81.6%) with CT and US in only 12 (25%) and 4 (8.3%) patients, respectively. The staging accuracy of EUS amounted to 80% in T1-, 81% in T2-, 100% in T3-, and 67% in T4-stage. The sensitivity in demonstrating lymph node metastases was 81.3% for EUS, 25.8% for CT and 9.7% for US. The specificity in this regard was 72.2% for EUS, 83.3% for CT and 100% for EUS. The overall accuracy for determination of pN-stage was 78% for EUS, 47.9% for CT and 41.7% for US. EUS is clearly superior to CT and US in the locoregional TN-staging of gastric carcinoma. PMID- 8465548 TI - [Coronary vessel anomalies in adults--harmless variation or changes with clinical significance]. AB - A review of 1097 consecutive coronary angiograms performed for evaluation of angina pectoris or valvular dysfunctions showed 3 patients with arteriovenous fistulas (0.25%), 6 patients with malpositions (0.55%), 29 patients with aneurysms (2.65%) and 59 patients with myocardial bridging (5.4%). The clinical significance of coronary artery anomalies as variation or malformation was evaluated. A malformation has been found in Bland-White-Garland syndrome, arteriovenous fistulas, congenital coronary stenosis and atresia. In case of clinical symptoms surgical correction should be considered. There is a controversy on the clinical significance of muscular bridging. Further clinical investigations are needed for a better understanding of coronary artery anomalies. PMID- 8465549 TI - [Results of animal experiments with videodensitometry in the assessment of gastrointestinal motility]. AB - It is possible to register video-densitometrically the gastrointestinal motility visible in fluoroscopic image using a video-signal analyser. The influence of metoclopramide at the propulsive movement of the stomach wall of rats was checked in vivo. The propulsive gastric movement increased in case of small doses of metoclopramide, higher doses stopped the motility. The propulsive gastric movement is parallel to the evaluation of the stomach. Metoclopramide has only a mild influence on the contraction frequency. We found that videodensitometry is also a practical method for evaluation of local wall motility of an intestinal segment of a rabbit. The non-visible motion is recorded and evaluated by means of several physical parameters (frequency, moving velocity of waves). Videodensitometry does not supply information on the causes of motion; hence, a combination with other methods, i.e. the registration of the electromyogram (EMG), is useful. In this way the mechanical answer to EMG-changes is simple to quantify. The experiment with rabbits affords a proof regarding the practicability of the method for pharmaco-physiological investigations. PMID- 8465550 TI - [General practice-oriented forms of education of the 18th century. On the 250th anniversary of the birth of Johann Friedrich Gottlieb Goldhagen (1742-1788)]. AB - Widely differing conditions applied to practice-oriented medical teaching at universities in the various German principalities or territorial states in the 18th century. Initially, the institutions used by professors as "collegium clinicum" belonged either to foundations or were being run on a private basis. It was only in the second half of the 18th century that these institutions became state-supervised, with the inclusion of the discipline of surgery. The results of such reorganization are demonstrated, taking Halle and the work done by Johann Friedrich Gottlieb Goldhagen as examples. PMID- 8465551 TI - [The public health structure regulation]. PMID- 8465552 TI - The 13C-urea breath test--detection of Helicobacter pylori infection in patients with partial gastrectomy. AB - The 13C-urea breath test (13C-UBT) for diagnosis of Helicobacter pylori (Hp) infection was evaluated in 41 patients after partial gastrectomy and was used for determination of the Hp-prevalence after two different procedures of reconstruction of the gastrointestinal tract, i.e. Billroth's II operation and Roux-en-Y anastomosis. Breath samples were taken at various time points within 30 minutes after a motility inhibiting liquid test meal with citric acid followed by 75 mg of 13C-urea. The 13CO2/12CO2-ratio (delta-value) was measured using isotope ratio mass spectrometry and the recovery of tracer in the exhaled breath was calculated (UBT-value). In all patients and in the corresponding control groups comparison of established reference methods (culture, CLO test, and Fuchsin staining) with the 4 point breath analysis for detection of Hp was investigated. In patients with partial gastrectomy, the sensitivity of the 13C-UBT to detect the presence of Hp and the negative predictive values were 100%, whereas the specificity and the positive predictive values were about 80%. In patients without gastric surgery quality control parameters were not significantly different. Hp-prevalence in postoperative patients was about 45%. All results were independent of their expression either as delta-value or as UBT-value and were not significantly different between the patients with Billroth's II operation and the patients with Roux-en-Y anastomosis. In conclusion, the 13C-UBT is a suitable method for diagnosis and therapeutic monitoring of Hp-status in patients after partial gastrectomy. PMID- 8465553 TI - Polyamine deficiency impairs proliferation and differentiation of cultured enterocytes (CaCo-2). AB - The polyamine dependence of enterocyte growth and differentiation was studied in the human intestinal cell line CaCo-2 using a specific inhibitor of the key enzyme ornithine decarboxylase (ODC), difluoromethylornithine (DFMO). ODC was highest during the initial phase of rapid growth and was inhibited in a dose dependent fashion by DFMO at 0.06-2 mM. At low levels DFMO only delayed cell replication without affecting final cell count whereas at concentrations of 0.125 mM and above the final cell number was diminished by at least 53% compared to controls. In contrast, DFMO even at 0.03 mM reduced sucrase activity to 44% of controls when added at day 2 but was ineffective when supplemented at day 7 of culture or later. The inhibitor also diminished the number and length of microvilli in a dose dependent fashion, although this effect required higher DFMO levels than the reduction of sucrase activity. The DFMO mediated suppression of cell replication, enzymatic and morphologic differentiation was reversible in the presence of the ODC product putrescine. Putrescine alone did not affect any of the above parameters. In conclusion, the present data suggest that ODC and polyamines are involved both in enterocyte growth and differentiation. PMID- 8465554 TI - Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn's disease with special respect to chronic diarrhea--a pilot study. AB - In a randomized, single-center, double-blind, placebo-controlled pilot study, 20 patients with established Crohn's disease suffering from diarrhea and moderate complaints as measured by the BEST Index, were treated with the yeast preparation Saccharomyces boulardii (S.b.) in a dosage of 250 mg t.i.d., initially for two weeks in addition to the basic treatment. A reduction in the frequency of bowel movements (5.0 +/- 1.4 vs. 4.1 +/- 2.3 evacuations/day, p < 0.01) and in the BEST Index (193 +/- 32 vs. 168 +/- 59, p < 0.05) as compared to baseline was registered. After this initial phase, the patients were allocated in randomized order to the control group (n = 7) receiving placebo, or to the verum group (n = 10) receiving S.b.(250 mg t.i.d.) for 7 weeks, while the basic treatment was maintained. The group treated with S.b. showed a significant reduction in the frequency of bowel movements in the tenth week, to 3.3 +/- 1.2 evacuations per day, and in the BEST Index, to 107 +/- 85. In the control group taking placebo, however, this effect was not observed. By contrast, the frequency of bowel movements and the BEST Index rose again in the tenth week until reaching initial values (4.6 +/- 1.9 evacuations daily and 180 +/- 61, respectively). No adverse drug events were observed. In order to confirm these positive effects of S.b. in patients with Crohn's disease, further controlled multicenter trials in a larger patient population should be performed. PMID- 8465555 TI - Laxative use not a risk for colorectal cancer: data from the Melbourne Colorectal Cancer Study. AB - Commercial laxative use as a risk factor in colorectal cancer was investigated as one part of a large population based epidemiological study of colorectal cancer incidence, aetiology and survival "The Melbourne Colorectal Cancer Study", conducted in Melbourne, Australia. Commercial laxative use was similar in 685 colorectal cancer patients and 723 age/sex matched community based controls. Also, when laxatives were subdivided into various groups containing anthraquinones, phenolphthalein, mineral salts and others, previous laxative intake was similar between cases and controls. Previous use of anthraquinone laxatives and of phenolphthalein containing laxatives was not associated with the risk of colorectal cancer. PMID- 8465556 TI - [Collagenous sprue--a rare form of celiac disease in adulthood]. AB - The authors report a case of collagenous sprue. This condition is characterized by coeliac type small bowel malabsorption, resistant to gluten free diet and other therapeutic efforts, associated with poor prognosis. The diagnosis depends on the histological demonstration of extensive collagenization of the lamina propria in the flat jejunal mucosa. This disease must be kept in mind at differential diagnosis of chronic diarrhea with progressive malabsorption, especially if it is resistant to gluten withdrawal in contrast to conventional coeliac disease. PMID- 8465557 TI - [The common channel syndrome in adults]. AB - Congenital abnormalities of the distal bile and pancreatic duct occur predominantly as a long common channel. A common channel of more than 15 mm is considered abnormal, since the length allows a reflux of pancreatic secretion into the bile duct and vice versa. The very rare occurrence of a long common channel syndrome in adults has been observed in two female patients (24 and 58 years old). Both presented cholangitis and/or pancreatitis. Diagnosis was established by ERCP. The definitive therapy in both cases was hepatico-jejunal anastomosis which improved symptoms in both patients. Endoscopic sphincterotomy is unsatisfactory since it does not cut the entire common channel. The rare etiology of a long common channel in patients with cholangitis and pancreatitis is safely verified by ERCP and safely cured by surgical intervention. PMID- 8465558 TI - [Mini-endoscopy of the bilio-pancreatic system]. PMID- 8465559 TI - [The effects of bile salts in the duodenum on exocrine pancreatic secretion: stimulating, inhibiting or both?]. PMID- 8465560 TI - [Recurrent and acquired hepatitis C virus infection in patients after liver transplantation]. PMID- 8465561 TI - [Comment on the contribution: "The diagnostic value of the amino acid absorption test in detection of disordered exocrine pancreas function" by Kemmer et al]. PMID- 8465562 TI - [Guidelines for patient monitoring in endoscopic examinations in gastroenterology. The German Society of Digestive and Metabolic Diseases]. PMID- 8465563 TI - [Behavior of various activity-controlled cardiac pacemakers in treadmill stress tests with variable slopes]. AB - New activity pacemaker systems with the principle of sensing low-frequency acceleration in the anterior-posterior axis are currently under clinical evaluation. We compared the pacemaker system Relay, which represents this new generation of accelerometer controlled devices, with conventional activity systems sensing pressure and vibration. Ten pacemaker patients with implanted Activitrax, Sensolog or Relay pacemakers and 10 healthy volunteers with externally strapped-on pacemakers were studied. The aim was to evaluate the systems' ability to distinguish different workloads during graded treadmill testing with changes in speed and/or slope. The rate adaption of the new acceleration sensing pacemakers was found to be more adequate compared to vibration and pressure-sensing pacemakers when only the slope of the treadmill was varied. The acceleration-sensing pacemaker adjusted its rate according to the workload largely independent from the type of stress (n.s.). With the vibration and pressure-sensing pacemakers, however, significant differences (p < 0.05) were seen between rate adaption in the two stress test modes. The new generation of acceleration-sensing pacemakers has certain advantages over conventional vibration-sensitive systems in terms of a higher sensitivity to varying workloads and higher specificity to the type of exercise performed. PMID- 8465564 TI - [Ventricular macro-reentry tachycardia of the bundle branch type--indications for catheter ablation]. AB - Out of 115 patients with recurrent sustained monomorphic ventricular tachycardia who underwent catheter ablation between August, 1987 and May, 1992, 7 were found to have bundle branch reentry. Bundle branch reentrant tachycardia was assumed if His potential or bundle branch potential preceded ventricular activation during tachycardia with identical H-H'- and V-V'-intervals. In 5 patients, catheter ablation of the right bundle branch and in 2 patients, ablation of the proximal left bundle branch were performed with direct current or radiofrequency energy. The procedure was successful in all 7 patients. During the follow-up of 15 +/- 12 months, 3 patients died due to cardiac failure. One patient had sustained ventricular tachycardia 12 months after catheter ablation which was not due to bundle branch reentry and was treated with an implantable cardioverter/defibrillator. Atrioventricular conduction delay in the surface electrogram and during electrophysiologic study may give a hint at bundle branch reentrant ventricular tachycardia since it was seen in 5 of our 7 patients. Catheter ablation of one bundle branch is an effective treatment which can prevent recurrence of this tachycardia. PMID- 8465566 TI - [Antegrade balloon valvuloplasty of critical aortic stenosis in an infant weighing 1,820 g]. AB - A case of antegrade balloon-valvuloplasty in an 34-day-old premature 1820 g baby with a critical aortic stenosis is reported. After transseptal puncture of the interatrial septum a loop was formed within the apex of the left ventricle. In order not to endanger the anterior leaflet of the mitral valve a maximum distance to the mitral valve was maintained. After two antegrade balloon-dilatations the pressure gradient over the stenotic aortic valve was reduced from 80 mmHg to 15 mmHg. No hemodynamic relevant aortic regurgitation occurred. Antegrade balloon valvuloplasty in critical aortic stenosis represents an alternative to the retrograde technique. Severe laceration of the ileofemoral arteries, which has been reported in up to 45% of all retrograde procedures, is avoided in antegrade balloon-dilatation. Comparatively, the antegrade passage of the catheter through the stenotic aortic valve is easily performed. No dislocation of the balloon occurs during antegrade valvuloplasty. Through this procedure the aortic occlusion-time is reduced to a minimum. Besides protection of the arterial vessels, reduction of the aortic occlusion-time seems to be an important advantage of this technique when compared with the retrograde approach. PMID- 8465565 TI - [Interventional high frequency perforation and enlargement of the outflow tract of pulmonary atresia]. AB - In 18 patients with pulmonary atresia interventional perforation of the atresia was attempted using radiofrequency. All patients were referred for palliative surgery. The age ranged from 4 days to 19 years. After angiographic delineation of the relations between the right ventricular outflow tract and main pulmonary artery the tip of a radiofrequency perforation catheter (Cerablate-catheter, 2F, Osypka) was brought into contact with the atresia. The radiofrequency was applied in the unipolar fashion (radiofrequency-generator HAT 200, Osypka). Radiofrequency perforation was successfully performed in 14/18 patients, subsequent balloon dilatation was performed in 12 of these patients. In six patients with muscular atresia a Palmaz-stent was implanted into the right ventricular outflow tract. An inadvertent perforation of the right ventricular outflow tract occurred in three patients, of the pulmonary artery in two patients. However, these were tolerated without sequelae or clinical symptoms. The arterial oxygen saturation increased by 21%; in none of the patients was cardiac failure or pulmonary edema observed. Using the Cerablate-catheter even muscular atresias could be perforated. Implantation of a stent into the newly created right ventricular outflow tract results in a predictable communication between the right ventricle and the pulmonary artery. Although this interventional right ventricular outflow tract creation seems to be a promising new technique, experience is limited and there are no long-term results. PMID- 8465567 TI - [Left cerebral ischemia in mitral valve aneurysm]. AB - An anterior mitral leaflet aneurysm was detected by two-dimensional echocardiography using the transesophageal approach in a 53-year-old patient with cerebral ischemic event. The transesophageal examination allowed a clear description of the aneurysm which was confirmed during surgery. This case demonstrates that transesophageal echocardiography is the method of choice in evaluation of distinct valvular lesions. The importance of TEE examination in patients with a neurological history is evident. PMID- 8465568 TI - [Trends in patient composition before PTCA and bypass operation. Implication for secondary prevention and rehabilitation. Report of the discussion group 23 April 1992 within the scope of the spring meeting of the German Society of Cardiovascular Research]. PMID- 8465569 TI - [Multicenter results of coronary implantation of balloon expandable Palmaz-Schatz vascular stents]. AB - Intracoronary stenting was designed to handle acute vessel closure after balloon angioplasty and to reduce the rate of restenosis. In three cardiology centers the implantation of 200 balloon-expandable Palmaz-Schatz stents was attempted in 179 patients. The implantation was successful in 170 patients (95%). During bail-out implantation for acute vessel closure or symptomatic dissections after balloon angioplasty, implantation succeeded in 60 (91%) of 66 attempted patients, who recovered immediately from ischemia. Three patients received emergency bypass surgery and three patients were kept on medical therapy. Restenosis after 4 to 6 months, defined as > 50% diameter reduction, was documented angiographically in 18 (15.3%) of 118 presently controlled patients. Patients with single stent implantation (n = 106) presented a late restenosis rate of 10.4% in contrast to patients with multiple stent implantation (n = 12), who presented a restenosis rate of 58.4%. Similar results on restenosis were found for patients with elective and bail-out stent implantation. Acute thrombotic stent occlusion occurred in three patients (1.8%) during the first 24 h after stenting. Three to 9 days after implantation subacute stent thrombosis occurred in 15 (8.8%) of 170 patients. Despite adequate therapy including thrombolysis, balloon angioplasty or emergency bypass surgery in 14 of 15 patients Q-wave myocardial infarction was documented in six patients and non Q-wave myocardial infarction in five patients. The following parameters were identified as risk factors for the development of subacute stent thrombosis: bail-out indication, unstable angina, type C lesion, stenosis length > 1.5 cm, plaque area > 3.5 mm2, symptomatic dissection after balloon angioplasty, incomplete wrapping of the dissection after stenting and residual distal vessel irregularities after stenting. Bleeding complications occurred in 12.4% of the patients and were related to the anticoagulation and antiaggregation therapy. In conclusion, the implantation of Palmaz-Schatz stents is an excellent bail-out device to treat acute vessel closure or symptomatic dissections after angioplasty. Elective and bail-out single stent implantation is associated with a reduced rate of restenosis when compared to conventional balloon angioplasty. At present, subacute stent thrombosis and bleeding complications are the major limitations with a combined rate of 15.9%. PMID- 8465570 TI - [In vitro studies of shock wave effects during ablation of normal and atherosclerotic vascular wall by excimer laser]. AB - Ablation of atherosclerotic plaque and normal arterial wall was performed using a xenon-chloride-excimer laser with a wavelength of 308 nm and a pulse duration of 115 ns. The light was transmitted via a 600 micron fiber and adjusted to an energy density of 3.5 J/cm2. The acoustic signals generated by the laser pulse were measured with hydrophones consisting of polyvinylidenefluoride with active diameters of 0.3 mm and recorded on a dual-channel digital storage oscilloscope using either a 0.5 m coaxial cable or a broadband transmission system. From 19 cadavers human aortic tissue segments were excised and macroscopically classified as either normal or calcified atherosclerotic plaque. Approximately 500 measurements were performed in saline and blood each. Histological analysis was carried out after the experiments to verify the macroscopic diagnosis and to correlate the acoustic responses with the tissue characteristics. For "normal" arterial segments, maximum peak pressure was 1.25 MPa +/- 0.85 MPa, rise time 163 ns +/- 43 ns, and pressure increase 8.2 kPa +/- 5.4 kPa/ns in saline. For calcified, atheromatous segments a significantly higher maximum pressure (2.20 MPa +/- 1.16 MPa), a significantly shorter rise time (69.9 ns +/- 25.8 ns), and a significantly higher pressure increase (32.3 kPa +/- 21.3 kPa/ns) was found in saline (p < or = 0.0001). In blood, maximum peak pressure was 1.29 MPa +/- 0.43 MPa, rise time 93.3 ns +/- 27.7 ns, and pressure increase 14.6 kPa +/- 5.2 kPa/ns for "normal" arterial segments. Maximum peak pressure (2.28 MPa +/- 0.63 MPa) and pressure increase (32.8 kPa +/- Pa/ns) were significantly higher for calcified tissue segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465571 TI - [Subepicardial hematoma (haemorrhagia per rhexin) after elective PTCA with consecutive compression of the distal RIVA]. AB - A transmural coronary dissection occurred immediately after elective angioplasty of a 90% stenosis of the proximal left anterior descending coronary artery (LAD) within the dilated segment and was followed by subepicardial bleeding (haemorrhagia per rhexin), although no perforation by the guide-wire or the balloon catheter took place. A subepicardial blood bolster led to rapid extravasal compression of the LAD distal from the PTCA site resulting in acute ischemia. None of the conventional rescue-interventions such as stents or autoperfusion catheters were likely to resolve this critical situation and the patient successfully underwent emergency bypass surgery. PMID- 8465572 TI - [Cardioverter-defibrillator implantations without thoracotomy: clinical experience with various electrode configurations and defibrillation wave forms of an endocardial/subcutaneous defibrillator system]. AB - Twenty-seven consecutive patients with refractory ventricular arrhythmias were investigated for implantation of an nonthoracotomy cardioverter-defibrillator lead system. Supply with a nonthoracotomy lead system could be achieved in 25 of 27 patients (92.5%), while implantation proved impossible in two patients due to elevated defibrillation thresholds. After implantation of an endocardial defibrillation electrode no differences were found compared to the implantation of an endocardial defibrillation electrode with a subcutaneous chest wall defibrillation patch with regard to the defibrillation thresholds obtained for monophasic defibrillation waveform. Supply with an endocardial defibrillation lead system was successful in 18 of 25 patients (72%). Ten consecutive patients with implantation of an endocardial defibrillation lead system alone were compared for defibrillation efficacy following monophasic and biphasic defibrillation waveforms. Defibrillation with biphasic waveforms led to a decrease in the necessary defibrillation energy from 19 J (4.6 J) to 10 J (4.0 J). There was occurrence of refractory ventricular fibrillation that could not be controlled by endocardial and transthoracic defibrillation in two patients during the intraoperative testing of defibrillation thresholds. In both cases these arrhythmias could be terminated by the described method of endocardial/extrathoracic defibrillation (200 J). Further perioperative complications were not observed. Over a mean follow-up of 6.8 (1-17) months all patients demonstrated regular functioning of the cardioverter-defibrillator. Dislocation of defibrillation electrodes did not occur. Implantation of a cardioverter-defibrillator can be performed without thoracotomy in the majority of cases. The use of defibrillator systems with biphasic waveform widens the scope for implantation of nonthoracotomy defibrillating lead systems. PMID- 8465573 TI - [Diseases of the musculoskeletal system in the elderly]. PMID- 8465574 TI - [Polyarthritis in the elderly]. AB - Ten to thirty-three per cent of all cases of rheumatoid arthritis (RA) develop after sixty years of age. Late-onset RA patients are more likely to be male, to have faster onset of symptoms, to experience shoulder and hip disease initially, and to have higher erythrocyte sedimentation rates; they are less likely to develop rheumatoid nodules, extraarticular manifestations, positive serologic tests, or unfavorable outcomes. There are roughly three patterns of late-onset RA: a classical form which resembles typical adult-onset RA; a limited, fairly mild form in which Gougerot-Sjogren syndrome often coexists; and a form in which the shoulders and hips are involved first. The latter form, whose early stage closely resembles polymyalgia rheumatica (PMR), accounts for approximately 25% of cases, is very specific of elderly patients, and is difficult to differentiate from PMR. RS3PE (Remitting Seronegative Symmetrical Synovitis with Pitting Edema) is a different entity from RA. PMID- 8465575 TI - [Subacute benign edematous polyarthritis in the elderly]. AB - Subacute edematous polyarthritis of the elderly is a recently described syndrome. The condition is characterized by its sudden onset and by the presence of important edema of the four limbs, symmetrical polyarthritis, marked inflammatory syndrome, and negative serological test for the rheumatoid factor. Men are predominantly affected, and many of them are carrying the HLA B-7 antigen. The illness subsides within a few months without sequelae. It seems that this syndrome should be clearly distinguished from late onset rheumatoid arthritis and polymyalgia rheumatica. PMID- 8465576 TI - [Aging phenomena and arthrosis]. AB - The incidence of arthroses has a highly significant correlation with age. However, a clearly defined relationship from a causal basis does not yet exist. This association is not through the time-dependent accumulation derived from the mechanical "destruction-quantum" at a molecular level in the cartilage. Indicative for the transformation is progressive degeneration with considerations of disease values, norms, and biochemical parameters of the joint and associated indicators. We use the example of the knee joint to illustrate this point. The discrepancy over deficit in strength and regulatory mechanisms is also considered, as well as the passive chondroprotective shock-absorption of the subchondralia spongiosa, and, conversely, the apparent protective mechanism of osteoporosis preceding arthrosis. Epidemiologically, osteoporosis and arthroses have been proven incompatible; what remains to be elucidated is the well-known dichotomy in their courses of development. PMID- 8465577 TI - [Polymyalgia rheumatica]. AB - Giant cell arteritis-mediated polymyalgia rheumatica is a typical disease of old age; though manifestation is rare in patients younger than 50 years, there is no upper age limit. Average disease-onset is at age 70. Typical symptoms and high serological inflammation are found. Laboratory data is nonspecific; temporal artery biopsy is imperative in unclear cases. Only glucocorticoid therapy initiates prompt pain relief, stops the inflammatory process and apprehends vascular complications. Monitoring of therapy requires careful guidance and experience. PMID- 8465578 TI - [Crystal-induced arthropathies]. AB - The formation and deposition of crystals in articular tissues increases with growing age. As a consequence crystal-induced or crystal-associated arthritides or arthropathies can be observed particularly in the elderly where these disorders comprise a considerable part of inflammatory joint diseases. Gout, induced by monosodiumrate crystals mostly presents as acute monarthritis, less frequently as a chronic polyarthritis. Calciumpyrophosphate deposition may induce acute pseudo-gout, rheumatoid-arthritis-like (pseudo-rheumatoid) arthritis and a variety of other clinical syndromes. Basic calciumphosphate crystals may be associated with acute and chronic recurrent or destructive arthropathies. The detection of crystals in joint fluids by polarized microscopy as well as typical X-ray-findings allow to make a diagnosis in the context of characteristic clinical features. In addition to the antiinflammatory treatment it is important to detect and treat underlying metabolic disorders. PMID- 8465579 TI - [Senile osteoporosis--prevention and therapy]. AB - Senile osteoporosis (type II-osteoporosis) is the final result of a large number of risk factors and negative effects on bone tissue which affect the skeleton throughout life. Important phases include bone formation during childhood and adolescence, the following obligatory loss of bone substance in the process of bone remodeling, periods of increased bone loss due to individual risk factors and augmented bone resorption in advanced age. According to this complex pathogenesis affecting the skeleton throughout life prevention is a lifelong task. The most important measures include a high calcium diet, regular physical activity, avoidance of risk factors and in postmenopausal women long-term sequential estrogen-progesteron substitution. The primary goal of therapy of established osteoporosis in the elderly is to relief symptoms and pain. Further treatment with the aim to keep or even increase bone mass (e.g. calcitonin, fluoride, calcium) may be indicated in individual patients taking into consideration age, disease activity and other individual prognostic factors. PMID- 8465580 TI - Anti-rheumatic treatment in the elderly. AB - The elderly are more liable to problems from drugs used systemically. An accurate diagnosis may reveal conditions in which drug treatment is not required, especially those due to faulty habits and environmental problems, and local conditions susceptible to injections or surgery. Obesity, sepsis, hypothyroidism, osteomalacia, unsuspected fractures and drug side-effects may give correctable rheumatological problems. Use of analgesic anti-inflammatory drugs needs great care in the elderly; use analgesics instead when possible. Rheumatoid arthritis in the elderly demands maximum use of nonpharmacological treatment and local treatment. Analgesic anti-inflammatory drugs should be used carefully and sparingly. Use slow-acting drugs as in younger patients. PMID- 8465581 TI - [Characteristics of physical therapy in diseases of the musculoskeletal system in the elderly]. AB - Physical therapy is application of different kinds of energy for treatment. It provokes reactions by stimulation using physiological principles. Physical measures induce immediate effects as well as long-term reactions with adaptation. In diseases of the locomotor system in higher age, physical therapy is applied for diminishing pain and stiffness, amelioration of metabolism and function and especially for the maintenance of functional independence. Also fitness, good health and self-confidence can be stimulated. The age-dependent pecularities of the locomotor system, the skin and the cardiovascular system should be taken into consideration. Each method of physical treatment (hydrotherapy, heat and cold treatment, massages, exercise treatment, electrotherapy) has its age-specific peculiarities, which should be known by the treating physician. Modification of treatment can become necessary also by the kind of the disease. Dosage and technics of physical therapy must be adapted individually and supervised carefully. PMID- 8465583 TI - [Aging, flexibility, training]. AB - The aging process is characterised by a reduction of the physical capacity of coordination, flexibility, strength, power, velocity and endurance. At the same time the kind of adaptation is modified. Details are described about the influences of aging on the cardio-pulmonary-metabolic system. In comparison to the internal organs the importance of training for alterations in connection with aging within the musculo-skeletal system are less known. Bones, cartilage, synovia, ligaments, and tendons are underlying also consequences of aging process. Strength and/or endurance training can help to reduce those negative influences. The description of exercises for the improvement of flexibility and coordination finishes the necessary program of training of the older and old men within the preventive medicine. PMID- 8465584 TI - Evaluation of arteriosclerosis progression with ultrasonic biopsy and intima media thickness measurements. AB - Noninvasive ultrasonic biopsy (UB) can be used to classify arteriosclerotic lesions and their progression in the carotid and femoral bifurcation. Six UB classes have been defined. The rate of progression (ROP) to the next UB class in four years has been defined in 1270 normal subjects: it was 1.4% from class I to class II, 3.1% from II to III, 10.7% from III to IV, 17.9% from IV to V and 79.2% from class V to VI. In high risk subjects (HRS)--305 hyperlipidemics, 269 diabetics and 381 hypertensives--the ROP in 4 years was significantly higher considering all classes. This finding was matched by a more significant increase in intima-media thickness (IMT) increase in HRS in comparison with normal subjects. In conclusion UB and IMT measurements can be used to monitor arteriosclerosis progression. HRS have a comparable increase in ROP and IMT in four years indicating rapid progression in comparison with normals. UB appear to be more effective in evaluating progression when plaques and wall irregularities make IMT measurements difficult. PMID- 8465582 TI - [Critical life change events and adjustment in a group of elderly single women]. AB - Women that were children or adolescents during World War II have rarely been studied in psychological and sociological research. Because of the death of over 3.5 million German men in that war, there remained many single (especially, never married) women of corresponding age. In a research project at the University of Munster some psychological and social aspects of the life situation of never married, employed women born between 1919 and 1933 in comparison to married women of the same age that had never been employed were studied by means of detailed interviews. Parts of the results concerning the retrospective experience of critical life events and coping strategies are described. The results indicate that the interviewees were confronted with difficult life events, but that they coped with them in a very active way. Differences between women of different martial statuses (e.g., for the never-married women a more frequent mentioning of events concerning the war, a higher involvement in personal health problems, a lower importance of their occupation than expected by the authors, and, for example, for the married women a higher family-centeredness) are discussed. PMID- 8465585 TI - [Color-coded duplex ultrasound and contrast medium enhanced duplex ultrasound in deep venous thrombosis]. AB - Even with highly developed ultrasound systems, diagnosis of deep leg vein thrombosis is difficult in lower leg veins and in the area of the adductor channel. In order to evaluate color duplex-sonography, contrast media duplex sonography and phlebography in comparison, 79 patients (38 men and 40 women aged 54 to 89) with deep leg vein thrombosis were examined. As a result, patients suffering from thrombosis were characterized by a vein-artery quotient of > 2.0 (p < 0.01). In color Doppler duplex-sonography false negative findings occurred in 12 cases of lower leg vein thrombosis and in 3 cases of thrombosis within the adductor channel. By contrast media duplex-sonography the diagnostic reliability could be increased to a sensitivity of over 95 per cent. PMID- 8465586 TI - [Differences in prognoses of aorto-iliac and femoro-popliteal reconstructions in peripheral arterial occlusive disease. Results after at least 15 to 25 years]. AB - The results of 729 extremities, operated for peripheral vascular disease and followed for at least 15 up to 29 years are presented. 457 aortoiliac reconstructions are compared with 272 in the femoropopliteal area. All patients suffered only from intermittent claudication. The two groups were compared as to patency rate, reocclusion, amputation rate and mortality. It is of great interest, that the great majority of patients dying in the follow up have open reconstructions and have taken therefore advantage of surgery in being free of walking difficulties up to their death. The results of aortoiliac reconstructions are better, the patency rate is higher, the amputation rate lower, but even femoropopliteal reconstructions do better and have lower amputation rates than in natural course of the disease. Patients with intermittent claudication below 50 years of age should not be admitted to femoropopliteal surgery, because the risk of amputation before death is higher. PMID- 8465587 TI - [Endoscopic perforant vein revision. Current status]. AB - Blind dissection of incompetent perforators is common practice for vein surgeons. Since many years some of them have been trying to do this endoscopically by means of the proctoscope or other endoscopes used for different purposes. At present, however, several surgeons are developing special instruments for this type of endoscopy. Lately some of these surgeons came together to work up their experiences and to study the probable future of the method. It permits the diagnosis and at the same time the treatment of incompetent perforators. It allows the healthy ones to be spared. All this can be done from a small incision distant to the site of the perforators where the skin often presents with trophic changes. However, general or regional anesthesia as well as the bloodless limb technique are prerequisites. As any endoscopy also this one has its specific dangers and complications and therefore has to be learned and performed carefully. PMID- 8465588 TI - [Long-term results of unsuccessful thrombolysis and secondary thrombectomy of deep leg-pelvic vein thromboses: a critical analysis]. AB - According to the literature, fibrinolytic therapy of acute thrombosis of the pelvic and deep lower leg fails in about 15%. As the primary patency rate correlates with the long term results, we intended to investigate whether the failures of 15% might be improved by a secondary thrombectomy. 87% of 31 thromboses treated by secondary thrombectomy were investigated by clinical, morphological and functional examinations. The data show that in case of the intervention taking place within 8 days (total age of the thrombus including the period of lysis treatment) the results were excellent, within 8-14 days they were still good. Patients below the age of 30 years benefited most by the therapy. However, the postulated "airtight effect" could not be demonstrated. Early diagnosis is of paramount importance. The period of lysis treatment should be limited and in case of failure a secondary thrombectomy should be offered to the patient. PMID- 8465589 TI - [Long-term results of percutaneous transluminal angioplasty and stent implantation in venous stenoses following transfemoral thrombectomy]. AB - Thirty consecutive patients were operated on for iliofemoral venous thromboses. In each case, a transfemoral thrombectomy was performed and an arterio-venous fistula was created. Three to six months later, a cross-over arterio-venography revealed 10 severely stenosed venous segments in 8 patients (common iliac vein 4, external iliac vein 3, common femoral vein 3). All stenoses were treated by percutaneous transvenous angioplasty (PTA). Six times a flexible, self-expanding Wallstent was placed within the stenosis after dilation (PTA+S). Complications did not occur. Median follow up was 17 months (3-23 months). PTA+S proved superior (4/6 excellent results) when compared to PTA alone (1/4 excellent result), because of frequent restenosis after the latter. Minor results following PTA+S were caused by intimal hyperplasia within the stent, when the av-fistula was kept patent for more than a year after stent placement. PMID- 8465590 TI - [Ablation of venous valves with Nd-Yag laser--an alternative to conventional valvulotomy?]. AB - The careful removal of venous valves during in situ venous bypass procedures is a problem that has not been completely solved. In this experimental study, valve ablation with the Nd-Yag laser was compared with conventional valvulotomy. The investigation was performed in vitro using human vein segments with a length of 20 cm. Conventional valvulotomy was performed 16 times, 20 valves were removed with a 400 mu-fibre and 26 with the hot tip. The results were evaluated by endoscopy, light and electron microscopy. There were no vein perforations with the valvulotome and the hot tip. Endothelial damage was documented in 85% with the valvulotome and was reduced significantly to 58% with the 400 mu-fibre. With the hot tip endothelial lesions were seen in only 30%. Valve remnants were always present with the valvulotome and in no more than 15% with the hot tip. Electron microscopy supported these results in general. There was no endothelial damage in 69%. PMID- 8465591 TI - [Aorto-enteric fistula]. AB - Between 1974 and 1991 six patients with an aortoenteric fistula were treated. A primary aorto-jejunal fistula was successfully operated. The other 5 cases were suffering from secondary fistulas due to aortoiliac reconstructions. None of these patients survived. The diagnostic procedures, therapy and prophylaxis are discussed. PMID- 8465592 TI - [Metabolic changes after transperitoneal vascular interventions]. AB - Thirty patients who had undergone transperitoneal vascular surgery were examined for hormonal disturbances and alterations of energy and protein metabolism. Of all hormonal alterations only the increased level of insulin activity in the early postoperative period is clinically important. The higher oxygen consumption and carbon dioxide production together with the increased protein turnover indicate an elevated energy expenditure. In order to prevent decompensation of the hypermetabolic metabolism, a reduced nutritional support after major vascular surgery is justified. PMID- 8465593 TI - [Long-term follow-up of Mobin-Uddin umbrella filter implantation for prevention of pulmonary embolism]. AB - A follow-up of 40 cases of Mobin-Uddin-umbrella implants for prophylaxis of secondary pulmonary embolism is presented. The all-over lethality was 35% (14 patients) including one embolic recurrence. 25 patients could be re-examined 0.2 11.1 years after the implantation, using the patient's history, clinical examination, native X-ray of the umbrella, B-scan of the inferior vena cava, phlebodynamometry of the legs, spirometry, ergometry, manometry of the pulmonary artery pressure. Possible or probable recurrences of embolism were recorded in 15% (5 patients). The umbrella was totally occluded in 48% and partially occluded in 23%. Umbrella-related complications due to faulty insertion were not observed. Patients without additional cardiopulmonary diseases did not show pulmonary hypertension or ventilatory disorders at rest. 86% of the patients suffered from a symptomatical chronic venous insufficiency of one or both legs. Today the Mobin Uddin-umbrella has been replaced by other percutaneously applicable cava filters. However, their application may also be followed by complications. Therefore the decision to use cava filters of any type should be based on severe selection criteria. PMID- 8465594 TI - [Severe Raynaud disease of all four extremities]. AB - A 64-year-old woman presented with a serious Raynaud's disease affecting all four extremities and resulting in fingertip necroses. The symptoms had initiated after her second pregnancy in association with anorexia requiring treatment in a psychosomatic clinic and necessitating parenteral feeding. After successful sympatholysis a sympathectomy was performed. After initial success a recurrence in the right arm was treated by intraarterial prostaglandin infusion. This treatment brought a temporary benefit whereas intravenous infusions had been without effect. A further medical blockade of the stellate ganglion was followed by a complete disappearance of the symptoms. A subsequent re-operation was performed. Since all the cervical branches of the sympathetic nerve cord had been resected during the first intervention, a partial resection of the stellate ganglion (ganglion cervical inferior) was performed. There was a temporary benefit which lasted a few months. Medical long term treatment was unsuccessful. However, no further necroses occurred and the intermittent pain is tolerable. PMID- 8465595 TI - [Current status of combined physical decompression therapy in primary and secondary lymphedema of the legs]. AB - Clinical lymphology has become an important part of angiology. Patients suffering from lymphedema are in need of physicians and physiotherapists who guide them trough this chronic disease and who are familiar with the different complications of chronic lymphatasis. The necessary experience in the treatment of lymphedema of the lower extremities can be achieved only at lymphologic treatment centers with adequate numbers of such patients. Nihilism concerning therapy of these disorders is not justified as our experience with the enumerated combined physical drainage therapy demonstrates. PMID- 8465596 TI - [Aneurysm spurium after resection of aortic coarctation]. AB - 25 years after reconstruction of an aortic coarctation by prosthetic material, an insufficiency of the anastomosis gave rise to the development of a false aneurysm. The aneurysm was resected and the anastomosis was reconstructed in parallel extracorporal circulation with femoral cannulation in order to prevent ischemic lesions of the spinal cord and the visceral organs. The patient who works as a circus acrobat, made a successful recovery. PMID- 8465597 TI - [Unilateral "nevoid" spider nevi]. AB - A case of unilateral spider telangiectasia on the left side of the face initiating at puberty is reported. With respect to its therapy and prognosis this alteration must be distinguished from other telangiectasias. With unilateral nevoid telangiectasia it shares the unilateral distribution of the lesions and the predilection for the female sex during hormonal instability periods. Both of these types of acquired telangiectasia seem to occur in relation with endocrine influences. Unilateral nevoid telangiectasia may also show typical spider telangiectasia but occurs in combination with other telangiectatic alterations. Unilateral "nevoid" spider telangiectasia consists exclusively of spider telangiectasia. Pathogenesis and further differential diagnosis of this peculiar type of primary telangiectasia are outlined. PMID- 8465599 TI - [The new Frankenstein]. PMID- 8465598 TI - [Recurrent acute occlusions of the popliteal artery before age 50: popliteal entrapment syndrome?]. AB - Compression of the popliteal artery by the medial head of the gastrocnemius muscle is termed "Popliteal Artery Entrapment". The anatomical course of the artery can be normal or abnormal. The entrapment can cause occlusion of the artery or peripheral embolism. This syndrome is an important differential diagnosis in younger patients with recurrent peripheral arterial ischemia. Diagnosis is made by history, clinical findings, arteriography and CT-scan of the knees. All cases of popliteal artery entrapment, whether the artery is occluded or not, should be operated on. PMID- 8465601 TI - Cloning and genetic analysis of the gene encoding a new protein kinase in Saccharomyces cerevisiae. AB - We have isolated a single gene from the yeast Saccharomyces cerevisiae encoding a potential 800 amino acid polypeptide of calculated M(r) 90,098 Da. This protein consists of an N-terminal region that shares significant homology with the catalytic domains of several serine- and threonine-specific protein kinases, as well as a large, unique, C-terminal domain of unknown function. Haploid disruption mutants are viable and do not exhibit any readily observable growth defects under varying conditions of temperature, nutrients or osmotic strength. Due to the apparent structural similarity between this kinase and the protein products of the KIN1 and KIN2 genes, we have chosen to name this new gene KIN3. PMID- 8465600 TI - Galactose inhibition of the constitutive transport of hexoses in Saccharomyces cerevisiae. AB - The relationship between the pathways of glucose and galactose utilization in Saccharomyces cerevisiae has been studied. Galactose (which is transported and phosphorylated by inducible systems) is a strong inhibitor of the utilization of glucose, fructose and mannose (which have the same constitutive transport and phosphorylation systems). Conversely, all these three hexoses inhibit the utilization of galactose, though with poor efficiency. These cross-inhibitions only occur in yeast adapted to galactose or in galactose-constitutive mutants. The efficiency of galactose as inhibitor is even greater than the efficiencies of the other three hexoses to inhibit the utilization of each other. Phosphorylation is not involved in the inhibition and the transport of sugars is the affected step. The cross-inhibitions between galactose and either glucose, fructose or mannose do not implicate utilization of one hexose at the expense of the other, as it occurs in the mutual interactions between the latter three sugars. It seems that, by growing the yeast in galactose, a protein component is synthesized, or alternatively modified, that once bound to either galactose or any one of the other three hexoses (glucose, fructose or mannose), cross-interacts respectively with the constitutive or the inducible transport systems, impairing their function. PMID- 8465602 TI - Cloning and genetic characterization of a calcium- and phospholipid-binding protein from Saccharomyces cerevisiae that is homologous to translation elongation factor-1 gamma. AB - We have isolated a gene (CAM1) from the yeast Saccharomyces cerevisiae that encodes a protein homologous to the translational cofactor elongation factor-1 gamma (EF-1 gamma) first identified in the brine shrimp Artemia salina. The predicted Cam1 amino acid sequence consists of 415 residues that share 32% identity with the Artemia protein, increasing to 72% when conservative substitutions are included. The calculated M(r) of Cam1p (47,092 Da) is in close agreement with that of EF-1 gamma (M(r) = 49,200 Da), and hydropathy plots of each protein exhibit strikingly similar profiles. Disruption of the CAM1 locus yields four viable meiotic progeny, indicating that under normal growth conditions the Cam1 protein is non-essential. Attempts to elicit a translational phenotype have been unsuccessful. Since EF-1 gamma participates in the regulation of a GTP-binding protein (EF-1 alpha), double mutants with cam1 disruptions and various mutant alleles of known GTP-binding proteins were constructed and examined. No evidence was found for an interaction of CAM1 with TEF1, TEF2, SEC4, YPT1, RAS1, RAS2, CDC6, ARF1, ARF2 or CIN4. The possibility that Cam1p may play a redundant role in the regulation of protein synthesis or another GTP-dependent process is discussed. PMID- 8465603 TI - The role of ALA-S and ALA-D in regulating porphyrin biosynthesis in a normal and a HEM R+ mutant strain of Saccharomyces cerevisiae. AB - Catabolite repression and derepression on delta-aminolevulinate synthase (ALA-S) and delta-aminolevulinate dehydratase (ALA-D) in a normal yeast strain, D27, and its derived D27/C6 (HEM R+) were investigated. ALA-S and ALA-D activities and intracellular ALA (I-ALA) at different physiological states of the cells were measured. In YPD medium, under conditions of repression and when glucose was exhausted, both strains behaved identically as if the mutation was not expressed. In YPEt medium, however, both ALA-S and ALA-D activities were higher than in YPD, but the I-ALA content and the enzymic activity profiles shown by the two strains were quite different. It appears, therefore, that the mutation causes a deregulation of ALA-S, so that its activity is kept at a high level throughout the cell cycle. This would explain the increased levels of cytochromes present in the mutant. This mutation may affect some regulatory aspect of ALA formation and renders an ALA-S of high activity; moreover, this enzyme species seems to be more stable than in the normal strain. PMID- 8465604 TI - The VPH2 gene encodes a 25 kDa protein required for activity of the yeast vacuolar H(+)-ATPase. AB - Strains bearing the vph2 mutation are defective in vacuolar acidification. The VPH2 gene was isolated from a genomic DNA library by complementation of the zinc sensitive phenotype of the mutant. Deletion analysis localized the complementing activity to a 1.2 kb DNA fragment. Sequence analysis of this fragment revealed the presence of a single open reading frame that encoded a protein of 215 amino acids. Computer analysis indicated that the protein, which has a predicted molecular mass of 25,286 Daltons, has two distinct membrane-spanning domains. Biochemical studies indicated that strains bearing the vph2 mutation have greatly reduced levels of vacuolar proton pumping and ATPase activity and that the nucleotide binding subunits of the multimeric vacuolar H(+)-ATPase failed to be correctly targeted to the vacuolar membrane. The vph2 mutant fails to grow on YEP glycerol medium and on media containing 100 mM-CaCl2 or 4 mM-ZnCl2 or buffered to pH 7.5, a phenotype observed in strains carrying deletions in the genes encoding several vacuolar H(+)-ATPase subunits. The VPH2 gene is identical to the VMA12 gene (T. Stevens and Y. Anraku, personal communication). PMID- 8465605 TI - CNE1, a Saccharomyces cerevisiae homologue of the genes encoding mammalian calnexin and calreticulin. PMID- 8465606 TI - The complete sequence of a 19,482 bp segment located on the right arm of chromosome II from Saccharomyces cerevisiae. AB - We report here the sequence of a 19,482 bp DNA segment of chromosome II of Saccharomyces cerevisiae. The fragment contains 16 open reading frames (ORFs) covering 74% of the sequence. Four predicted products present homology with known proteins. The ORF YBR1732 exhibits a strong homology to serine hydroxymethyl transferase; the best score is 53.1% identity in 458 amino acids overlap with the serine hydroxymethyl transferase from rabbit liver. YBR1724, which shows homology with riboflavin synthase of Bacillus subtilis, is probably the RIB5 gene implied in riboflavine synthesis and mapped in this region. YBR1733 is homologous to rab protein and YBR1728 is presumably a GTPase activating protein. PMID- 8465607 TI - [Chemical composition of eight edible mushrooms]. AB - A comparative analysis of crude protein, crude ash, phosphorus (P), potassium (K) and calcium (Ca) contents of 57 samples of eight common edible mushroom species was made. The most important protein sources were: Marasmius oreades and Lepista nebularis. Species of the Boletaceae formed an intermediate group, while relatively proteinless species were: Armillariella mellea and Cratarellus cornucopioides. The lowest crude protein content was established in Cantharellus cibarius. The ash contents varied more widely. The greatest P contents were measured in Lepista nebularis and Marasmius oreades but most mushrooms contained 6-7 gP/kg. The analysed mushroom samples contained 30-40 gK/kg dry weight and 0,2 0,3 gCa/kg. These analyses are important from the point of view of the nutritional role of mushrooms. PMID- 8465608 TI - Microbiological status of rabbit carcases in Egypt. AB - A total of 40 New Zealand white rabbits, 20 freshly slaughtered rabbits from an experimental farm and 20 processed rabbit carcases from grocery stores in Beni Suef city, were examined bacteriologically. The mean values of aerobic plate counts at 37 degrees C and 1 degrees C, Enterobacteriaceae counts, Pseudomonas counts and Staphylococcus counts of freshly slaughtered rabbits were 10(4) +/- 2 x 10(3), 8 x 10(2) +/- 10(2), 6 x 10(2) +/- 10(2), 3 x 10(2) +/- 10(2), and 10(2) +/- 60 organisms per gram respectively, whereas the equivalent values were 8 x 10(5) +/- 3 x 10(4), 2 x 10(5) +/- 10(4), 4 x 10(4) +/- 8 x 10(3), 2 x 10(4) +/- 6 x 10(3), and 4 x 10(3) +/- 4 x 10(2) organisms per gram of processed rabbit carcases from grocery stores, respectively. The freshly slaughtered rabbits showed a low bacterial load compared with processed rabbit carcases from grocery stores. Escherichia coli and Listeria monocytogenes could be isolated from the rabbit carcases examined in addition to Salmonella typhimurium, Pseudomonas aeruginosa and Staphylococcus aureus from processed rabbit carcases. Yersinia enterocolitica could not be isolated from any sample examined. Suggested measures to reduce the microbial load in rabbit carcases are discussed. PMID- 8465609 TI - Selenium distribution in egg white proteins. AB - The present studies were undertaken to characterize selenium distribution in egg white. Ion-exchange chromatography fast protein liquid chromatography (FPLC) and flow injection atomic (absorption) spectrometry (FIAS) were used to separate egg white proteins and to determine the selenium content of different fractions. After purification, nine different proteins were identified with sodium dodecyl sulphate-polyacrylamide gel electrophoresis and 56% of the total selenium content was found to be associated with ovalbumin-1 and -2 (+/- 500 ng/g), which is the main protein in egg white. Flavoprotein was determined to be the richest selenium containing protein (1800 ng/g). The selenium content of the other proteins (lysozyme, conalbumin, globulins and ovomucoid) ranged from 359 to 1094 ng/g. PMID- 8465610 TI - Disulphide bonds in wheat gluten: further cystine peptides from high molecular weight (HMW) and low molecular weight (LMW) subunits of glutenin and from gamma gliadins. AB - Glutenin was prepared from gluten of the wheat variety Rektor by extraction of gliadin with aqueous ethanol. It was cleaved successively into soluble peptides by the enzymes trypsin and thermolysin. Separation of the peptide mixtures was performed by gel permeation chromatography (GPC) on Sephadex G25 and reversed phase high performance liquid chromatography (RP-HPLC) on ODS-Hypersil. Cystine peptides were detected by differential chromatography of the samples prior to and after reduction. After isolation by multi-step RP-HPLC, the cystine peptides were reduced. The resulting cysteine peptides were alkylated with 4-vinylpyridine, separated by RP-HPLC and sequenced by means of the Edman degradation. The isolated cystine peptides represented a considerable portion of the total cysteine in glutenin: four out of seven cysteine residues of HMW subunits, and eight out of nine cysteine residues of LMW subunits are documented by at least one cystine peptide. Most of the peptides corresponded to known sequences of gluten protein components. From the structures of some tryptic peptides, inter- and intramolecular disulphide bonds for HMW subunits of glutenin have been proven. Cystine peptides from the thermolytic digest have been assigned to LMW subunits of glutenin and to gamma-gliadins. Other peptides have been closely related to partial sequences of these protein components. The results have allowed several conclusions about the arrangement of intra- and intermolecular disulphide bridges in gluten proteins. PMID- 8465611 TI - Polymerase chain reaction (PCR): a possible alternative to immunochemical methods assuring safety and quality of food. Detection of wheat contamination in non wheat food products. AB - A rapid, sensitive and specific analysis of food samples determining wheat contamination was established using polymerase chain reaction (PCR) technology. First, primers specific for highly conserved eukaryote DNA sequences were used to prove isolated nucleic acid substrate accessibility to PCR amplification. Subsequently, a highly repetitive and specific genomic wheat DNA segment was amplified by PCR for wheat detection. This assay was tested with 35 different food samples ranging from bakery additives to heated and processed food samples. In addition, the PCR method was compared to an immunochemical assay that detected the wheat protein component gliadin. Combination of both assays allowed a detailed characterization of wheat contamination. Hence, wheat flour contamination could be distinguished from gliadin used as a carrier for spices as well as from wheat starch addition. PMID- 8465612 TI - [Information on surgical risk--proper timing]. PMID- 8465613 TI - [Treatment of breast cancer "one hundred years ago"]. PMID- 8465614 TI - [Therapeutic consequences of early detection of locoregional recurrences in breast cancer]. AB - The value of follow-up investigations depends on the therapeutic consequences of early detection of recurrences and metastatic disease. After breast conservation early detection of recurrent disease by physical and apparative examinations has to be aimed for due to a possible curation by salvage surgery. Also in recurrences of the chest wall a great deal of local controls can be achieved when detected early and at smaller sizes. While axillary recurrences can be controlled by surgery and radiation therapy the prognosis is poor in the case of a supraclavicular and retrosternal lymph node involvement. Diagnostic and therapeutic options will be discussed for these five types of recurrences. PMID- 8465615 TI - [Spectrum and effectiveness of emergency care by surgeons acting as rescue unit surgeons in a large city]. AB - From 1.1. 1985 to 31. 12. 1990 n = 10,569 emergency cases were prospectively documented. The aim of the study was to evaluate, whether surgeons on a mobile emergency care and rescue unit were able to treat surgical and non-surgical emergencies sufficiently during the prehospital period. 16.8% of the patients were trauma patients while 47% suffered from medical disorders, e.g. myocardial infarction (12%), other cardiocirculatory disorders (7%) and acute opiate and multidrug poisoning (16%). Additionally, other problems out of the broad spectrum of emergency medicine such as disorders from pediatrics, neurology/neurosurgery, gynecology, toxicology, pulmonology, endocrinology etc. had to be solved. More than 50% suffered from life-threatening emergencies, 5.6% required cardio pulmonary resuscitation, 45% of which were primarily successful. In-field deaths where emergency treatment was not successful occurred in 3.2%. The mortality rate during transport to the next available hospital was 0.1%. It can be concluded from the study that well trained surgeons are very capable to perform high efficient in-field emergency treatment for various disorders. PMID- 8465616 TI - [Changes in surgery of diverticulitis]. AB - This retrospective study investigates the surgical progress in the treatment of diverticular disease during the last two decades. We reviewed 304 patients (149 women and 155 men) operated for diverticular disease from 1970-1992 at the Surgical Clinic of Steglitz Medical Center, Free University of Berlin. Comparing the results between the first and the second decade, we observed a significant increase in the total number of patients who have been treated surgically (from 118 to 186) and in the proportion of elective surgery (from 45% to 57%). In the second decade, early elective resection in selected patients with a severe diverticulitis and primary resection for perforated diverticulitis were the procedures of choice. Through this concept the over-all operative mortality rate could be reduced from 24% in the first to 7% in the last decade of this report. PMID- 8465617 TI - [Diagnosis and therapy of cecal diverticulitis]. AB - Acute pain in the lower right side of the abdomen caused by caecal diverticulitis is very rare and hardly to distinguish from acute appendicitis. Therefore it is usually diagnosed intraoperatively. We report our experience with 12 patients, who received surgical treatment from 1984 to 1991. The diagnosis was made not before operation in 11 cases. Because of a severe inflammation of the caecal wall we performed an ileocaecal resection in 10 cases, in 2 cases it was necessary to perform a right hemicolectomy because of additional diverticulitis of the ascending colon. The surgical resection of the inflammatory mass was followed by an uncomplicated postoperative healing in all cases. PMID- 8465618 TI - [Deep rectovaginal fistula and incontinence after labor trauma]. AB - The commonest cause of traumata to the organ of continence is the injury during childbirth. Specially after negligent or missing reconstruction apart from incontinence rectovaginal fistulas can arise. This report deals with 24 incontinent women with a perineal laceration. After delivery 17 women had developed a low rectovaginal fistula. In addition to clinical recording of the incontinence, the proctological examination including anal manometry was carried out before and 25 months after surgery on an average. All patients get the same operation: Section of the anterior commissure, cutting out the fistula if necessary, separated suture of the animalic and voluntary sphincter, vaginal plasty. Preoperative resting pressure was 30 cm H2O and the voluntary pressure 46 cm H2O-on an average. Postoperative there was an increase to 61 cm H2O for the resting pressure and to 77 cm H2O for the voluntary pressure. 22 patients reported an improvement. 13 women are completely continent, 7 x soiling, 2 x incontinence for flatus, one incontinence for liquid stool and one stool incontinence were found. One fistula occurred again during follow up. Our surgical procedure compared with others has the advantage to give similar results avoiding protective colostoma. Besides the option for an other surgical procedure is still remained. PMID- 8465619 TI - [Renal effects of adenosine: possible consequences for kidney transplantation]. AB - This review summarizes in the first part the action of adenosine on the kidney. In the second part we discuss the pathophysiological consequences and the possibilities of a pharmacological intervention to improve impaired kidney function. Adenosine causes vasoconstriction in the kidney and reduces glomerular filtration rate (GFR). This action is enhanced in proportion to elevated plasma renin activity. Chronic elevation of ureteral pressure enhances and reduction of renal perfusion pressure attenuates adenosine-induced vasoconstriction. From the kidney-specific relationship between renal blood flow and tubular electrolyte transport the concept is developed which ascribes adenosine a role of a mediator that is essentially contributing to the homeostatic regulation of kidney function. The accumulation of adenosine in the kidney tissue after ischemia or after administration of nephrotoxic substances led to the hypothesis that adenosine is an important intrarenal factor in the pathogenesis of acute renal failure. The possibility to antagonize adenosine actions in the kidney with theophylline was used successfully in a number of experimental studies in acute renal failure and most recently in a study in humans after contrast media administration. Adenosine actions mediated via membrane receptors must be separated from adenosine actions in the cell to increase ATP tissue content. The concept of the "University of Wisconsin" (UW) solution to improve the energy state of the tubular cells appears to be successful, however, we propose that the potential dangerous adenosine actions in the kidney, especially during the reperfusion phase may be antagonized by the administration of theophylline. PMID- 8465620 TI - [Recent results regarding indications for the "morning after pill"]. AB - Results of interrogating 150 women who visited our department because of postcoital contraception are demonstrated. 80% did actually use one method of contraception. The rate of "condom accidents" was 70 per cent. Only 21 per cent did not use any method of contraception. Taking the facts of sexual habits into consideration we can conclude that women who wish to take the "morning after pill" have a more active sexual life. The intention to prevent an unwanted pregnancy through this postcoital method of contraception indicates a more responsible attitude towards sexuality. The popularity of this method may be increased. PMID- 8465621 TI - [Control of labor with prostaglandins after previous cesarean section]. AB - The authors studied the possibilities of vaginal labour management by induction after previous caesarean section. They compared the effectiveness of oxytocin and prostaglandins in uterus action. A total of 48 patients after previous caesarean section were induced, 26 by oxytocin and 22 by prostaglandins. The success of the induction was 30.7% with oxytocin and 95.4% with prostaglandins. Compared were also both the incidence of complications during labour and the effect of the uterotonic used on the fetus. It follows from the results that local application of prostaglandins is more advantageous than overall application and carries practically no risk for the patient in labour. PMID- 8465622 TI - [Correlation between cytogenetic anomalies of human spermatozoa and sperm morphology as well as age of patients studied]. AB - Sperm chromosomes from 15 fertile men were analyzed after fusion of their spermatozoa with zona-free hamster eggs. The total proportion of abnormal metaphases as well as the proportions of aneuploidy and structural aberrations were calculated for every man and examined for linear correlations with sperm morphology and the age of the persons studied. A positive correlation between the cytogenetic parameters and the percentage of abnormal sperm morphology was not evident, suggesting that assessment of sperm morphology cannot be used as an indicator of chromosomal damage in human spermatozoa. In contrast, there was a more distinct positive correlation between the age of donors and the three cytogenetic parameters studied. Analogous calculations for two other study groups (group S: male subfertility; group HA: habitual abortions of the wives with unknown etiology) provided less clear results that may be attributed to the lower number of patients or to the existence of special indications as mentioned above. PMID- 8465623 TI - [Dramatic reduction of the incidence of trichomonas vaginalis infections]. AB - In contrary to former meanings the trichomonas-vaginalis-infection doesn't play any longer an important role. Nowadays it even seems to be a rarity. So we found an infection-rate of 2.17% in 1979 (n = 4005), whereas in 1992 only in 0.19% (n = 1048). The possible causes for this pleasant development are discussed. Nevertheless a gynaecologist on principle should think of a trichomonas-vaginalis infection not only when her/his patients show specific symptoms as to burning, itching, discharge and dyspareunia, but in every case of discharge a trichomonas infection should be excluded-or diagnosed and treated specifically, in special cases even by culture. PMID- 8465624 TI - [Use of the hysteroscope in pediatric gynecology for diagnosis of vaginal hemorrhage and injury]. AB - The vaginal bleeding, injury and suspected foreign body are commonest indications for vaginoscopy in pediatric gynecology. A special hysteroscope, the resectoscope, permits the exploration of vaginal pathologies of girls with intact hymenal ring. Authors have used the resectoscope for vaginoscopy with excellent result. The small diameter, the magnification and the continuous fluid irrigation give ideal conditions for endoscopic evaluation of vaginal disorders in babies and virgins. The possibility of biopsy and coagulation is given by monopolar loop electrode. PMID- 8465625 TI - [First manifestation of non-Hodgkin's lymphoma in the labia major]. AB - In this report the case of an extranodal Non-Hodgkin's lymphoma with its manifestation in the external genitalia is described. The necessity of histological examination as well as the need of an cytostatic therapy is shown. PMID- 8465626 TI - [Lymph node metastasis in microcarcinoma of the uterine cervix]. PMID- 8465627 TI - [Maternal deficiency of IgG 2 and IgG 4 and neonatal infection caused by B streptococci]. AB - We describe here an newborn infant born in the 39th week of gestation with an early onset sepsis caused by group B streptococci. The intravenous administration of antibiotics and immunoglobulin preparation was unable to prevent the fatal outcome. The boy died after 16 hours of life. In the maternal serum a marked deficiency of IgG 2 and IgG 4 could be demonstrated. According to the results from the literature it seems possible that partial immunodeficiencies are important factors in the pathogenesis of the B-streptococcal disease of the newborn. PMID- 8465628 TI - The Bethesda System for reporting cervical/vaginal cytologic diagnoses: revised after the second National Cancer Institute Workshop, April 29-30, 1991. PMID- 8465629 TI - Fine needle aspiration biopsy in pediatric ophthalmic tumors and pseudotumors. AB - In an eight-year period (1983-1990) approximately 500 fine needle aspiration biopsies (FNABs) of eye lesions were processed in our laboratory. Eighty-one of the cases, obtained from 77 pediatric patients (ranging from 4 weeks to 16 years of age), were the subject of this study. The specimens included 73 intraocular and 8 orbital aspirates. Forty-four of the specimens were from diagnostic procedures, whereas 37 were obtained from surgical specimens immediately after enucleation. Eight FNABs (four diagnostic and four postenucleation) were deemed inadequate for cytologic diagnosis. Of the remaining 73 cases, 38 were diagnosed as malignant (34 retinoblastomas, 3 medulloepitheliomas, 1 rhabdomyosarcoma), and all were confirmed upon subsequent histologic examination. Four cases were diagnosed as suspicious for malignancy; all of them proved to be malignant (two retinoblastomas, two rhabdomyosarcomas). One orbital aspirate contained cells suggestive of a glial origin and was confirmed histologically as pilocytic astrocytoma. Ten cases were reported as compatible with Coats' disease; all were confirmed to be benign by histologic examination (three cases) or clinical follow up (seven cases). The remaining 20 benign aspirates (13 with inflammatory cells, 6 with macrophages and 1 with blood) proved to be from benign conditions by histologic examination (4 cases) or clinical follow-up (16 cases). There were no false-positive diagnoses. The overall accuracy of FNAB was 95%, and the accuracy of cytologic interpretation was 100%. We conclude that FNAB is a reliable and accurate diagnostic modality in the assessment of selected pediatric ophthalmic diseases. PMID- 8465630 TI - Fine needle aspiration cytology of oral cavity and jaw bone lesions. A report of 102 cases. AB - Fine needle aspiration cytology of oral cavity and jaw bone lesions was performed on 102 patients. The cytologic diagnoses were compared with the results of histologic examination. Thirteen of the 15 histologically malignant lesions and 71 of the 87 histologically benign lesions were cytologically diagnosed accurately. In 12 (92%) of the malignant and 69 (97%) of the benign lesions, specific cytologic diagnoses were given that proved the same or very similar to the final histologic diagnoses. This study showed that the overall accuracy of fine needle aspiration cytology in the oral cavity and jaw bones is high and is not significantly different from that obtained in other body regions. PMID- 8465631 TI - Fine needle aspiration cytology of cutaneous metastases. AB - By fine needle aspiration biopsy, 58 cases of cutaneous metastases were clinically and cytologically diagnosed at the Hines Veterans Administration Hospital from January 1987 to December 1990. Immunologic and electron microscopic studies affirmed the diagnosis and in some instances defined the primary neoplasm. The age of the patients ranged from 54 to 83 years (mean, 65). All were men. Two groups of patients emerged: group 1, 37 patients with known cancer, constituted the majority (64%). Group 2 consisted of 21 patients with cutaneous metastasis as the presenting sign (36%). Our patient survival times, a few weeks to 16 months (average, 4 months) are consistent with previous reports. PMID- 8465632 TI - Crystalline bodies in cervical smears. Clinicocytologic correlation. AB - We examined 6,132 cervical smears, applying strict criteria separating hematoidin cockleburrs from crystalline bodies. We found only crystalline bodies in 37 cases. There was a significant increase in the incidence of crystalline bodies in women taking oral contraceptives and in pregnant women. The bodies were not associated with an increase in complications of pregnancy or of abnormal births. A review of the literature led us to the conclusion that in cervical smears two types of crystalline structures may be found. One of these is the hematoidin body, which is related to hemorrhage during pregnancy and is probably associated with an increase in complications of pregnancy or abnormal births; the other, crystalline bodies, is not. We also conclude that crystalline bodies are much more common than hematoidin bodies. We found an unexpectedly high association of crystalline bodies with low grade squamous intraepithelial lesion (CIN1) in cervical smears. PMID- 8465633 TI - Comparison of morphologic features of benign hepatocytes associated with nonmalignant and malignant liver lesions. AB - In fine needle aspirates (FNAs) of focal liver lesions, the absence of neoplastic cells and presence of hepatocytes with prominent reactive changes often raise the question of whether the lesion was adequately sampled or whether the aspirate represents an area adjacent to the neoplasm. To study this problem we reviewed 51 FNAs of focal liver lesions: 29 metastatic deposits, 4 primary malignancies and 18 nonneoplastic lesions. Fifteen cytologic features were scored on a scale of 0 3 by two independent observers using conventional light microscopy. Hepatocytes in 18 aspirates of nonneoplastic lesions showed considerable degrees of cytoplasmic vacuolation, nuclear enlargement, cytoplasmic pigmentation, binucleation, anisonucleosis and intranuclear inclusions. In contrast, hepatocytes in 29 aspirates of metastatic deposits displayed a considerably lower degree of some of these features (cytoplasmic pigment, binucleation, anisonucleosis and nuclear enlargement.) The four aspirates of hepatocellular carcinoma showed nuclear enlargement of hepatocytes comparable to that in the nonmalignant aspirates; other accompanying features, however, were less conspicuous. We conclude that marked cytologic alterations in hepatocytes are seen most frequently in FNAs of nonneoplastic liver lesions, such as focal nodular hyperplasia, cirrhosis, abscess and hepatitis, and that hepatocytes accompanying metastatic deposits typically show less-pronounced cytologic alterations. PMID- 8465634 TI - Fine needle aspiration biopsy of the spleen in the evaluation of neoplastic disorders. AB - Splenic fine needle aspiration (FNA) biopsy has been used mainly in Europe to diagnose nonneoplastic systemic diseases. A few reports have described FNA biopsy of the spleen for the diagnosis of lymphoma. There is a definite paucity of North American reports concerning FNA biopsy for metastatic disease involving the spleen; that probably is a reflection of both the relative infrequency of splenic metastases and concern about potential hemorrhagic complications of the procedure. We report a series of 11 FNA biopsies of the spleen in patients with known carcinoma or hematologic malignancies. The FNA biopsies were performed on eight males and three females with a median age of 45 years and a range of 6-77 years. Six patients had a known hematopoietic malignancy at the time of aspiration (five non-Hodgkin's lymphoma, one acute myelogenous leukemia [AML]). The one patient with Hodgkin's disease had an FNA biopsy of the spleen as part of the initial workup; cytologic impression was atypical lymphoid cells with granulomas suggestive of Hodgkin's disease, which was confirmed by splenectomy. Four patients with carcinoma (two testicular, one lung, one ovarian) had FNA biopsies for the evaluation of splenic nodules; FNA biopsy confirmed metastatic carcinoma in three of these patients. In the entire series splenic FNA biopsy documented malignancy in 6 of the 11 patients. The one patient with AML had Aspergillus identified in the splenic aspirate, while granulomatous inflammation with yeast consistent with Candida was seen in a patient with non-Hodgkin's lymphoma. One aspirate demonstrated abscesses without recognizable organisms, and another showed extensive necrosis in a patient with testicular choriocarcinoma. Only one hemorrhagic complication was noted following splenic biopsy. Our experience demonstrates that FNA biopsy of the spleen is a useful and safe procedure in evaluating infectious and neoplastic splenic masses in patients with hematopoietic malignancies and carcinoma. PMID- 8465635 TI - Accuracy of urinary cytology in the diagnosis of primary and recurrent bladder cancer. AB - Two thousand two hundred thirteen smears of urinary specimens from 263 patients with bladder disorders were reviewed and the results correlated with the clinical status at the time of urine collection and with the histologic diagnosis during follow-up. In all cases a cytologic diagnosis of malignancy was histologically confirmed at follow-up, reflecting the high predictive value of a positive result in cytology. Cytologic diagnoses were also analyzed for the interval between the cytologic and histologic diagnosis of malignancy. In cases of cytologic diagnosis of malignancy, at times without a clinical suspicion of severe abnormality, an interval of up to 691 days was registered before a malignant process was confirmed histologically. Furthermore, the influence of tumor grade and mode of therapy on the diagnostic accuracy of urinary cytology was evaluated. The accuracy of urinary cytology differed clearly between untreated and treated patients with both high and low grade tumors. Patients who received surgical therapy, radiotherapy and chemotherapy were grouped into three groups. Accuracy of cytologic diagnosis was calculated in relation to variations in therapy and in tumor grade. Minor differences in accuracy were found between specimens from patients after surgical therapy, chemotherapy and radiotherapy. The data from this study suggest that the diagnostic accuracy of urinary cytology is very much related to the histologic grade of bladder tumors, to pretreatment and posttreatment status, and only minimally to the mode of therapy itself (e.g., radiotherapy, chemotherapy or surgical therapy). The high percentage of cytologic diagnoses of atypia in specimens from patients undergoing chemotherapy and radiotherapy reflects the diagnostic problems. PMID- 8465636 TI - Fine needle aspiration of abdominal fat for the diagnosis of amyloidosis. AB - Amyloidosis is a dysproteinemia characterized by extracellular deposition of amyloid fibrils. Its diagnosis depends on the demonstration of the characteristic apple-green birefringence in tissue stained with Congo red. Aspiration of subcutaneous fat as a means of procuring tissue has received attention in the internal medicine literature. However, this application of fine needle aspiration biopsy has not been investigated extensively by cytopathologists. We therefore report our experience. Over the past two years we performed 18 aspirations of subcutaneous fat on 17 patients in whom amyloidosis was clinically suspected. Eight aspirates were positive for amyloid, and nine were negative. There were no known false-negative results. False positives were more problematic, occurred early in our experience and were due to overinterpretation of occasional long, slender, green strands representing collagen. The true positives were all characterized by large numbers of short, apple-green strands intimately associated with the fat, oriented in multiple directions and occurring in much, if not all, of the aspirated fat. Attention to details of the aspirated material other than the presence or absence of apple-green birefringence can lead to a correct distinction between amyloid and collagen. We conclude that abdominal fat pad aspiration is useful in the workup of suspected amyloidosis, especially since it is a safe, easily performed procedure. PMID- 8465637 TI - Epidemiology of cervical carcinoma in Brunei Darussalam. Analysis of data on 27,208 women screened with cytologic examinations. AB - During the five-year period from January 1985 to December 1989 a total of 27,208 women, representing 44.0% of the total female population over age 15 years in Brunei Darussalam, underwent a cytologic examination. The majority of them were Malays (62.32%), followed by Chinese (22.23%), while the remainder were the expatriate population living in the country. High grade squamous intraepithelial lesion (moderate dysplasia) was detected in 88 women (3.3/1,000), high grade squamous intraepithelial lesion (carcinoma in situ) was seen in 32 women (1.22/1,000), and invasive carcinoma was found in 43 women (1.37/1,000). The overall detection rate for cervical cancer was 2.79/1,000 women in the population screened. In Brunei Darussalam Malay women marry at an early age, 44% by the age of 19 years, leading to sexual contact before the age of 20. However, the incidence of cervical cancer is low among them. This could be because they belong to the Orthodox Muslim Society, in which promiscuity is not permitted. Hence, multiple sex partners could be an important factor in the etiology of cervical cancer, confirming the current trend of thought that cervical cancer is a sexually transmitted disease. A comparison of the epidemiologic risk factors among the various races living in Brunei Darussalam is made. PMID- 8465638 TI - Helicobacter pylori infection. Rapid diagnosis with brush cytology. AB - The validity of brush cytology of the gastric mucosa with Diff-Quik rapid staining was studied in 69 samples, and its effectiveness was compared with two other techniques (culture and urease test). Brush cytology is the method of choice for detecting Helicobacter pylori since it is rapid, easy to perform and has good sensitivity and specificity. PMID- 8465639 TI - Sinus histiocytosis with massive lymphadenopathy. Report of a case with fine needle aspiration cytology. AB - Sinus histiocytosis with massive lymphadenopathy is usually a benign disorder with spontaneous remission, although a protracted clinical course with death has been reported rarely. The author reports a case diagnosed by fine needle aspiration cytology, the clinical utilization of which is discussed. PMID- 8465640 TI - Splenic fine needle aspiration biopsy in the diagnosis of lymphoreticular diseases. A report of four cases. AB - Splenic fine needle aspiration biopsy (FNAB) is rarely performed in the United States for several reasons: there is a perception that there is an increased risk of bleeding, and rendering a diagnosis of lymphoma (the most common primary splenic neoplasm) by FNAB is controversial. During a three-year period, we saw 11 cases of splenic FNAB. We present four cases of lymphoreticular neoplasms occurring between 1988 and 1991 in which the spleen was the only or most accessible organ in which to establish a diagnosis by FNAB: one case of small cleaved cell lymphoma, two cases of immunoblastic lymphoma (one T cell, one B cell by immunophenotyping studies) and one case of hairy cell leukemia in which the disease was confined to the spleen. All FNABs were radiologically guided, none of the patients suffered significant complications, and all had specimens sufficiently cellular to establish the diagnosis. Splenic puncture with FNAB may be an important and underutilized procedure for establishing a diagnosis in patients who have undetectable disease at other sites. PMID- 8465641 TI - Cytomorphology of subependymal giant cell astrocytoma. A case report. AB - Cytologic smears made from minute fragments of tissue removed during neurosurgical procedures are a useful alternative to frozen sections for rapid diagnosis. We describe the cytomorphologic features of a rare brain neoplasm, subependymal giant cell astrocytoma (SEGA). On cytologic grounds this neoplasm is difficult to separate from gemistocytic astrocytoma. The clinical presentations of the two neoplasms, however, are quite distinct, with SEGA an intraventricular neoplasm mostly seen in young adults with tuberous sclerosis, whereas gemistocytic astrocytoma occurs in the cerebral hemisphere of older adults. PMID- 8465642 TI - Fine needle aspiration biopsy of a cutaneous relapse of lymphomatoid granulomatosis. A case report. AB - We present the cytopathologic features of lymphomatoid granulomatosis in a case affecting the subcutaneous tissue. Atypical lymphocytes mixed with histiocytes and well-formed granulomas were the main findings. Fine needle aspiration biopsy can be a useful method of diagnosing subcutaneous relapses in lymphomatoid granulomatosis. To our knowledge, this is the first case report of these characteristics. PMID- 8465643 TI - Barium sulfate crystals in a fine needle aspiration biopsy specimen from a neck mass in a patient with squamous cell carcinoma. A case report. AB - A fine needle aspirate of a neck mass in a 79-year-old man with a previous laryngectomy for squamous cell carcinoma was submitted for examination. In addition to cytologic findings of squamous cell carcinoma, there were numerous birefringent crystals of varying shapes and sizes. Energy dispersive x-ray analysis confirmed that these crystals were barium sulfate. Recognition of barium sulfate crystals in a fine needle aspiration or other cytologic specimens is important since barium granulomas may mimic neoplasms clinically. Barium sulfate may also indicate rupture of an organ or the presence of a fistula. PMID- 8465644 TI - Primary aspergillosis of the breast. Report of a case with fine needle aspiration cytology diagnosis. AB - We report an unusual case of primary Aspergillus flavus fungal colonization in a subareolar breast mass in a middle-aged woman. The patient was clinically normal, with no evidence of immunosuppression. Fine needle aspiration cytology was carried out as a routine procedure to rule out malignancy, and Aspergillus infection was diagnosed on cytology. Cultures from fine needle aspiration cytology and the surgical biopsy material yielded a heavy growth of A flavus. The etiology and pathology of this fungal lesion presenting as a breast mass are discussed. PMID- 8465645 TI - Sebaceous variant of mucoepidermoid carcinoma of the salivary gland. A case report with cytohistologic correlation. AB - The findings on fine needle aspiration biopsy cytology of a case of sebaceous variant of mucoepidermoid carcinoma of the parotid gland are described. The aspirates consisted predominantly of uniform intermediate-type epithelial cells, which led to erroneous diagnosis of a benign neoplasm. The cytologic features of the intermediate, clear, mucinous and sebaceous cells were correlated with the different histologic patterns seen within the neoplasm. Problems encountered with the diagnosis are discussed. PMID- 8465646 TI - Diagnosis of primary nerve sheath tumor of the sphenoid sinus by fine needle aspiration biopsy. A case report. AB - This paper describes the aspiration cytologic characteristics of a histologically proven cellular schwannoma of the sphenoid sinus. The aspirate contained several large clusters of spindle-shaped cells in a compact, fascicular pattern. PMID- 8465647 TI - Hodgkin's disease beginning as a thyroid nodule. PMID- 8465648 TI - Respiratory epithelium in aspirates of thyroid gland lesions. PMID- 8465649 TI - Amyloid goiter in fine needle aspirates. PMID- 8465650 TI - Origin of foam cells in breast tissue. PMID- 8465651 TI - Nucleolar organizer regions in human maxillary sinus squamous cell carcinoma. AB - A silver colloid technique for nucleolar organizer regions (AgNOR) was applied to paraffin sections of maxillary sinus squamous cell carcinomas (MSSCC) of 25 patients. The patients were divided into two groups, one with MSSCC recurring in the primary lesion after treatment with radiotherapy, chemotherapy and/or surgery and one without recurrence. Notable differences between the numbers of NOR in neoplastic epithelia and the normal mucosa were observed (P = 0.0001), but there were no differences between the numbers of NOR in the recurrent and non-recurrent carcinomas. This investigation found no prognostic importance in the number of AgNOR in MSSCC. PMID- 8465652 TI - Gastric cytoprotection: morphological perspectives. AB - In 1979, a new mechanism of gastric defense named cytoprotection was followed by numerous reports elucidating this interesting and important phenomenon. During this decade, however, the concept and definition of gastric cytoprotection have been modified from the morphological and ultrastructural viewpoints. This review attempts to describe the concept and mechanisms of cytoprotection as well as its pathophysiological features. Specifically, in vitro studies using isolated cells or monolayer cultured cells as well as molecular investigations of signal transduction system have been documented. PMID- 8465653 TI - DNA ploidy and stromal bone formation as prognostic indicators of thyroid papillary carcinoma in aged patients: a retrospective study. AB - The prognostic value of flow cytometry for thyroid papillary carcinoma in aged patients was studied and compared with that of tumor histology. Seventy-five surgically removed primary papillary thyroid carcinomas larger than 30 mm in diameter were obtained from patients over 60 years of age. A subtotal thyroidectomy with modified radical neck dissection was performed in all patients. Sixteen female patients died of the carcinoma (non-survivors) and 18 survived longer than 12 years without recurrence (survivors). Histologically, papillary carcinoma was subclassified into poorly and well differentiated types, and the presence of stromal bone formation was noted. Flow cytometry was performed using paraffin-embedded materials. The incidence of the poorly differentiated type was 2/18 among the tumors of survivors and 6/16 among the tumors of non-survivors (P = 0.08). Stromal bone formation was only found in the tumors of the survivors (6/18 and 0/16; P = 0.014). In flow cytometry, tumors of the survivors showed a DNA diploid pattern (14/14), whereas half of the tumors of non-survivors (6/12) showed an aneuploid pattern (P = 0.004). Moreover, in the remaining six tumors of the non-survivors, two showed a third peak at 6C and one showed a higher S fraction. Therefore, only three showed a DNA diploid pattern that was indistinguishable from that of the survivors. These results suggest that flow cytometry is useful for estimating the prognosis of thyroid papillary carcinoma. PMID- 8465655 TI - Silver-binding argyrophilic nucleolar organizer regions (AgNOR) in gall-bladder cancer: correlations with malignant grading and prognosis. AB - Silver-binding nucleolar organizer regions (AgNOR) were investigated and compared in 43 cases of gall-bladder cancers and 10 normal gall-bladder samples using an image analyzer. The mean numbers of AgNOR per nucleus (AgNOR number) were 3.28 +/ 1.38 in the gall-bladder cancers and 1.86 +/- 0.20 in the normal gall-bladder cases. The respective mean areas of AgNOR per nucleus (AgNOR area) were 6.96 +/- 3.78 microns2 and 1.89 +/- 0.21 microns2. The differences were statistically significant (P < 0.0001) for both parameters. In addition, increased frequency and enlargement were both apparently correlated with poor prognosis (P < 0.011 and P < 0.046, respectively), with AgNOR number and AgNOR area showing tendencies for increase in cases of histologically high grade malignancy, advanced cancer and regional lymph node involvement. In conclusion, AgNOR number and AgNOR area appear to be useful indicators for the grading of malignancies and for the prediction of gall-bladder cancer prognosis. PMID- 8465654 TI - Pulmonary vasculature in idiopathic dilated cardiomyopathy: a morphometric study. AB - The pulmonary vascular alterations of seven patients with idiopathic dilated cardiomyopathy (IDC) were morphometrically examined, and the relation between the vascular alterations and morphological status of the hearts was studied. Most patients with IDC showed not only fibrous thickening of small pulmonary veins but also intimal circumferential fibrosis and medial hypertrophy of small pulmonary muscular arteries to various degrees. The histological features of the pulmonary vessels were compatible with hypertensive vascular changes observed in patients with mitral stenosis. There was a significant correlation between medial hypertrophy of the pulmonary muscular arteries and right ventricular hypertrophy. The pulmonary vascular changes in IDC were always associated with left atrioventricular dilatation, but were only found in patients with prominent hypertrophy of the left ventricles. Medial hypertrophy of the pulmonary muscular arteries was related more to left ventricular hypertrophy than to left ventricular dilatation. These findings suggest that the pulmonary vascular changes in IDC are caused by venous pulmonary hypertension, which may be developed at the late stage when left ventricular hypertrophy predominates. PMID- 8465656 TI - Clinicopathologic study of primary mediastinal non-lymphoblastic non-Hodgkin's lymphomas among the Japanese. AB - We studied the morphologic, immunologic and clinical features of 14 cases of primary non-lymphoblastic non-Hodgkin's lymphomas of the mediastinum. The patients ranged in age from 3 to 76 years, with a median age of 28 years. According to the Ann Arbor classification, 71% of our cases were in an early stage. Three cases were in Stage I, eight in Stage II, one in Stage III and two in Stage IV (one with multiple hepatic lesions and another with bone marrow involvement). The patients were heterogeneous in terms of the disease and were therefore histologically classified into three categories: diffuse large B cell lymphoma with sclerosis (DLS; n = 8); large cell anaplastic lymphoma (LC-Ana; n = 5); and low grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma; n = 1). DLS was the most common group and was characterized as CD5-, CD10-, CD19+, CD20+, CD21- and CD22+. Imprint smears showed azurophilic granules in the cytoplasm of the tumor cells of three of four DLS cases. All of the six cases examined were negative when tested for Epstein-Barr virus (EBV) sequences after hybridization with the EBV internal repeat probe. DLS and MALT lymphoma cases were of a B-lineage lymphoma of the thymus, while most of the LC-Ana cases were of a T-lineage lymphoma. Patients with non-lymphoblastic non-Hodgkin's lymphomas had a relatively favorable prognosis compared with lymphoblastic lymphoma (P < 0.01 by the generalized Wilcoxon test). There was no significant difference in the survival between non-lymphoblastic non-Hodgkin's lymphoma and Hodgkin's disease (P > 0.05 by the generalized Wilcoxon test). PMID- 8465657 TI - Multiple penetrating colonic ulcers in secondary amyloidosis caused by rheumatoid arthritis. AB - An autopsy case of multiple penetrated colonic ulcers with secondary amyloidosis caused by rheumatoid arthritis in a 61 year old woman is reported. Amyloid deposition was conspicuous in the transverse colon with numerous penetrating ulcers that were circumferentially scattered. Deposition was mainly in the small vessel walls of the submucosal layers. In the quantitative comparison of the histological components between the colonic segments affected by severe and mild ulcer formation, occlusive vascular amyloid deposition was revealed more frequently in the severe involved portion than in the mild involved portion. In addition, submucosal fibrosis that tended to appear around ulcers was more extensive and thicker in the former than in the latter. The complete vascular occlusion caused by amyloid deposition was particularly concentrated in the submucosal layer adjacent to the ulcer. These findings indicate that peripheral circulatory disturbance by amyloid deposition in the small vascular walls leads to ulcer formation in the colon. PMID- 8465658 TI - Inflammatory pseudotumor of the stomach: report of a highly infiltrative case with electron microscopic and immunohistochemical studies. AB - A large, poorly demarcated, elevated lesion over the area ranging from the lower end of the esophagus to the lesser curvature of the cardiac region was examined in a 19 year old woman, and demonstrated an irregular and highly infiltrative proliferation of spindle cells over the full thickness of the gastric wall. Although the spindle cells grew mainly in the submucosa, they penetrated the muscularis propria, leaving intact muscle tissue that formed an irregular, island like pattern, and reached the subserosa. The cells were identified as myofibroblasts by light microscopy, immunohistochemistry and electron microscopy. The present case is considered to be of an inflammatory pseudotumor due to extremely infiltrative growth of myofibroblasts. This lesion differed from inflammatory fibroid polyp (similarly consisting of proliferating myofibroblasts accompanied by inflammatory cells) in terms of age at onset, tumor size, pattern of cell proliferation and main inflammatory cell component. This report also discusses the relationship between this lesion and a very recently advocated new entity, inflammatory fibrosarcoma of the mesentery and retroperitoneum, which is a tumour closely simulating inflammatory pseudotumor. PMID- 8465659 TI - Primary leiomyosarcoma of the thyroid gland. AB - A primary leiomyosarcoma of the thyroid gland in a 72 year old Japanese woman is described. This is the second case reported in the English literature. The patient presented with a 7 month history of a gradually expanding tumor in the right neck. The surgical specimen taken by thyroid lobectomy revealed a relatively well demarcated tumor, 2 x 2 x 3 cm in size, confined to the right lobe. Histologically, the tumor showed a classical leiomyosarcomatous appearance of interlacing fascicles of spindle-shaped cells with occasional blunt-ended nuclei and a high frequency of mitotic figures. Immunohistochemistry of the tumor cells clearly showed smooth muscle differentiation; the cells were positive for desmin, muscle-specific actin and vimentin and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, thyroglobulin and calcitonin. The patient was free of disease for 3 years and 11 months without further treatment when evidence of multiple bone metastases appeared on bone scintigraphy. She died of pneumonia 4 years and 3 months after the lobectomy. PMID- 8465660 TI - An autopsy case of pulmonary artery leiomyosarcoma. AB - A case of pulmonary artery leiomyosarcoma in a 37 year old Japanese man is reported. The patient complained of chest pain and hemosputum. CT scan and angiography revealed that a tumor arose from the right main branch of the pulmonary artery. The surgical specimen was interpreted as an undifferentiated sarcoma at this time. The tumor recurred 6 months after the resection, and he died of right-sided heart failure. At autopsy, the pulmonary artery truncus was distended by the tumor, which protruded into the lumen. The tumor was composed of pleomorphic cells, giant cells and spindle-shaped cells. Many of the tumor cells were immunohistochemically positive for alpha-smooth muscle actin and vimentin. Electron microscopy revealed microfilaments with dense bodies in the cytoplasm and a discontinuous basement membrane around the cells. Although adenocarcinoma was also observed in the colon, the authors conclude that the present tumor is not a metastasis but a primary leiomyosarcoma arising from the pulmonary artery. Imaging techniques were very useful for differentiating sarcoma from thrombus in this site, and immunohistochemical demonstration for alpha-smooth muscle actin was necessary for making a histological diagnosis of leiomyosarcoma. PMID- 8465661 TI - Carcinoma of the gall-bladder arising in adenomyomatosis. AB - We describe a case of well differentiated adenocarcinoma of the gall-bladder that arose from a localized type of adenomyomatosis. Grossly, the cancer was located in the fundus and exhibited a polypoid and well demarcated nodule with multiple small cysts. Histologically, the nodule consisted of glandular structures and stroma containing bundles of smooth muscle cells. The glandular epithelia were varied in appearance, ranging from malignant to benign glands. The adenocarcinoma was limited to the nodule, with normal surface mucosal epithelia and without obvious stromal invasion. PMID- 8465662 TI - The round table in a community-based outpatient service. AB - The community-based outpatient service of Berne has used the round table for 8 years. It has become a strong element of the care of long-term outpatients. The aim of the present study is to examine how the round table is used and estimated by the patients: whether it only fulfils the function of a psychosocial contact facility to reduce social isolation or whether it has other helpful functions of social relationship. Further, we were interested to find out which of the therapeutic factors in group therapy are of importance. Four major factors could be elaborated by factor analysis: the functions and the importance of the caretakers at the round table, the acceptance and social integration of the patients and psychotherapeutic factors such as self-disclosure and vicarious learning. The round table is not only a social contact facility but also a new form of an informal, open, socio-therapeutic group. PMID- 8465663 TI - Autoimmunity in depression: increased antiphospholipid autoantibodies. AB - Some groups have recently reported higher titers of autoantibodies in depressed subjects than in normal controls. The present study investigates whether depressed patients exhibit increased antiphospholipid antibody titers compared with normal controls. The authors measured the binding index (BI) of antiphosphatidylserine (APSA), antipartial thromboplastin (APTA) and anticardiolipin (ACA) in 22 minor, 23 simple major and 20 melancholic depressives, 10 healthy controls and 104 normal controls with negative autoantibody sera. Depressed subjects exhibited significantly higher APSA and APTA antibody titers compared with normal controls. A large number of depressed subjects (+/- 54%) showed APTA and APSA positivity, defined as BI > or = 2 standard deviations above the mean BI of normal controls. There was a significant discrimination (> or = 2.8 standard deviations) between melancholic subjects and healthy controls with respect to BI of ACA, APSA and APTA. However, by using a more conservative value for phospholipid positivity (i.e., BI > or = 5 standard deviations above the mean BI of a reference sample of normal sera), the subject's autoantibody titers were, on the whole, within the normal range. Our results point towards a higher expression of antiphospholipid antibodies during depression but a much lower incidence of positive patients than in classical autoimmune disorders, such as systemic lupus erythematosus. PMID- 8465664 TI - Blinking, alpha brain waves and smoking in schizophrenia. AB - Blink rates (BR) and alpha brain waves were studied in 13 schizophrenic and 13 healthy smokers under conditions of smoking deprivation as well as smoking saturation and under different task conditions of smooth pursuit eye movements. Task conditions significantly changed BR and alpha power; smoking enhanced BR and alpha frequency, the latter effect being especially pronounced in schizophrenics for F3-F4 leadings. Concerning BR, groups differed significantly as long as smoking quantity was not statistically controlled. BR, alpha power and smoking quantity were consistently correlated above chance levels. Results are discussed with respect to the blink alpha neurocircuit model. PMID- 8465665 TI - Differences in P300 amplitudes and topography between cycloid psychosis and schizophrenia in Leonhard's classification. AB - In a polydiagnostic approach, we investigated the parameters of auditory P300 in a group of 18 remitted schizophrenics and in 18 age- and sex-matched controls. All patients fulfilled the criteria of schizophrenic disorder according to DSM III-R. Applying Leonhard's classification, patients were to be subdivided into 7 cycloid psychosis and 11 Leonhard's schizophrenics. Patients with cycloid psychosis fulfilled the operational criteria of Brockington et al. We found significantly lower P300 amplitudes in the group of Leonhard's schizophrenics than in controls and in cycloid psychosis, whereas no difference could be shown between patients with cycloid psychosis and controls. Both the maxima and the minima of the P300 field map were dislocated significantly to the right in the group of Leonhard's schizophrenics but not in cycloid psychosis. PMID- 8465666 TI - Life events and depression in Japan. AB - The relationship of life events to the onset of depression as well as the relationship between positive family history and reactivity to stress were investigated. Our results indicated that life stress in general plays an important role for women in the onset of depression and that undesirable events and problems of work specifically play a role in the onset of depression. The dichotomy of reactive and endogenous depression was not supported based on our result that no relationship was observed between the presence of familial loading and reactivity to stress. PMID- 8465667 TI - Comparative study of classification of psychosis of childhood and adolescent onset. AB - Classification of psychosis in childhood and adolescence has always been controversial due to the possible developmental modulation of symptom expression. Major classificatory systems have no special criteria for children, and recommend the use of adult criteria. Hence, this study aimed to study the nosology of psychosis of childhood and adolescence, using adult criteria (ICD-9, ICD-10 and DSM-III-R). Fifty subjects between the age of 5 and 16 years who met the ICD-9 definition of psychosis were studied using the Intake Sheet for Adolescents: cross-cultural study and the Interview Schedule for Children and Adolescents. Most of the subjects could be classified into one of the major functional psychosis categories, indicating the applicability of adult criteria in children and adolescents. PMID- 8465668 TI - The prevalence of mental disorders in school-age children attending a general paediatric department in southern India. AB - This study was conducted over a period of 18 months in a medical college hospital in southern India. Of 313 children of age 5 and above referred for detailed psychiatric evaluation, 101 were found to have a mental disorder according to DSM III-R criteria; the remaining had organic disorders. Children above 8 years (74%) registered higher morbidity. There was no sex difference in overall morbidity. Precipitating factors were discernible in half of these cases, of which school related problems were found in the majority. Almost two-thirds had multiple stressors, of which chronic family and social adversity (39%) and learning disabilities (28%) were common. Mental disorders were significantly related to urban background, middle-class socioeconomic status and literate parents compared with age- and sex-matched controls. There was no significant relationship with the type of family and number of siblings. Conversion disorder (31%) was the commonest, followed by conduct disorders (16%). The symptoms, stressors, response to treatment and the transcultural aspects are also discussed. PMID- 8465669 TI - Ethnicity as a risk factor for mental illness. A population-based study of 338 Latin American refugees and 996 age-, sex- and education-matched Swedish controls. AB - This article shows the influence of ethnicity on mental health compared with material factors and lifestyle, which are well-known risk factors for mental illness. The study was designed as a case-control study, with 338 Latin American refugees aged 16-74 years (response rate = 81.8%) in Lund, and a random sample of 996 age-, sex- and education-matched Swedish controls. The data were analysed unmatched with logistic regression in main effect models. The strongest independent risk mediator for mental illness was ethnicity, with an estimated odds ratio of 4.11 (2.31-6.92). Low material standard was associated with mental illness, with an odds ratio of 2.13 (1.07-4.11). Individuals who did not feel secure in daily life were at risk of mental illness, as were those with poor leisure opportunities. The combination of ethnicity, age over 44, and not feeling secure in daily life increased the odds ratio of mental illness to 26.62. Ethnicity, a low material standard, not feeling secure in daily life and poor leisure opportunities were significant risk factors for mental illness. PMID- 8465670 TI - Interhemispheric electroencephalographic coherence as a biological marker in alcoholism. AB - Electroencephalographic coherence scores in 21 teetotaler first-degree relatives of alcoholics, 27 subjects with alcohol dependence and 21 healthy subjects without a family history of alcohol abuse were compared. The relatives had significantly higher coherence scores in the frontal and parietal leads than the alcoholics and in the frontal and centroparietal leads than in the healthy subjects. This might represent a trait marker of resilience in subjects at high risk for the development of alcoholism. PMID- 8465671 TI - Abnormal perception of body weight is not solely observed in pubertal girls: incorrect body image in children and its relationship to body weight. AB - Perceived actual body weight and perceived ideal weight were assessed in 255 Japanese children and adolescents (130 boys, 125 girls) aged 6 years through 18 years using the drawing test to clarify whether they wanted to be thinner or to gain weight. More than half (68%) of the girls attending high school and 41% of the elementary school girls perceived their ideal weight to be less than the standard. The mean difference between the perceived actual weight and the ideal weight was positive in the high school girls of normal weight as well as in the overweight girls, meaning that even the normal-weight girls wanted to lose weight. The difference was also slightly positive in the underweight girls. The difference in the high school boys was negative, demonstrating that they wished to gain weight. It is suggested that girls want to lose weight even before adolescence; this tendency becomes more prominent in the high school period and is mostly unrelated to their own weight. PMID- 8465672 TI - Controlled intoxication treatment goals and procedures for alcoholics. PMID- 8465673 TI - Genetic models for the natural history of smoking: evidence for a genetic influence on smoking persistence. AB - We reanalyze data from the 1981 mailed questionnaire survey of the Australian twin register, to test for a genetic effect on smoking persistence (whether or not a smoker quits smoking). In the young cohort, aged 18-30 years, there are too few ex-smokers to permit resolution of genetic and non-genetic models. In the older cohort, we find a significant and substantial genetic effect on smoking persistence, accounting for 53% of the variance. This genetic effect on smoking persistence is independent of genetic effects on smoking initiation. PMID- 8465674 TI - Effects of situational demands on the direction of electrodermal activation during smoking. AB - Task demands (normal smoking; sham smoking; smoking or non-smoking during complex cognitive performance; and, smoking or non-smoking during monotonous vigilance performance) were manipulated in three experiments. Smoking increased electrodermal activity (EDA) arousal from pre-smoking baseline. Sham smoking (as a control for motoric aspects) also increased EDA arousal but to a lesser degree. In contrast the demands of complex cognitive performance were associated with lower EDA arousal during smoking than during non-smoking. Finally, during vigilance performance smoking maintained EDA arousal which during non-smoking decreased. Smoking did not improve performance during complex cognitive processing or vigilance above deprivation performance levels. It was concluded that smoking did have bidirectional effects as a function of task demand. However, there was no evidence that these physiological changes were functional and the smoking behavior data gave no indication as to the cause of these changes. PMID- 8465675 TI - Predicting alcohol use among young adults. AB - Factors influencing alcohol use among young people were studied using a questionnaire administered in Oklahoma and Wisconsin to 257 single males and 358 single females between the ages of 17-24. Predictors were broken down into the sets of demographics, family, religion, peer behavioral standards, approval of deviance, value of love and pleasure, and sex role variables. It was hypothesized that the predictors for alcohol use in males would differ from that of females. Data were analyzed separately for both male and female subjects. The multiple regression analysis found that the blocks of demographics, religion, peer behavioral standards, and approval of deviance were positive predictors for the use of alcohol in both males and females. The blocks, value of love and pleasure, and sex role variables were not found to be predictors of alcohol use in both males and females. Block number two (family) was found to be a predictor for females use of alcohol but not for males. PMID- 8465676 TI - Science and fascism: confronting unpopular ideas. PMID- 8465677 TI - Demographic, psychosocial and behavioral differences in samples of actively and passively consented adolescents. AB - Requiring active consent from parents leads to different self-reports by adolescents than when it is not required. The present study compares self reported demographic, psychosocial, and behavior variables between those students from whom active consent was and was not obtained. As found in previous studies, fewer minorities, fewer persons who were dissatisfied with school, fewer persons whose parents were of lower educational levels, and fewer cigarette smokers were represented in the sample recruited by active parental consent. Extending on previous work, we found those students whose parents failed to respond to the consent procedure were less likely to live with both parents, were more likely to be latch-key children, placed a lower priority on health, and were higher in risk taking, lower in self-esteem, and lower in assertiveness than those whose parents had responded. These data further support the suggestion that those children who are omitted from a research study because of lack of action on the part of the parent are at higher risk for a number of health and social problems. These children need to be included in evaluation samples in order to accurately assess the effectiveness of prevention programming. Future studies should employ a passive consent procedure as a means of recruiting a representative subject pool in school-based prevention research. PMID- 8465678 TI - Alcohol consumption and presenting problems in an out-patient mental health clinic. AB - Alcohol use has been shown to co-occur with a range of psychiatric disorders and psycho-social problems in both clinical and general population studies. The current survey of 683 out-patient mental health clients examined the relationship of self-reported alcohol use (as measured by the Quantity-Frequency index and the Retrospective Diary) with self-ratings of common mental health concerns. The South Shore Problem Inventory was developed as a brief self-report instrument to be used for routine assessment and research. The inventory yielded three factors after principal components analysis and Varimax rotation: affective/physiological signs and symptoms (Factor 1), interpersonal/family problems (Factor 2), and vocational/legal difficulties (including a self-rating of substance abuse) (Factor 3). MANOVA revealed that heavy drinking predicted significantly higher problem scores for all three factors. The SSPI showed good initial reliability and utility, and the three sub-scales were theoretically congruent with a social learning model of assessment. The use of similar problem scales and substance abuse indices can be used with a wider variety of both mental health and substance abuse treatment populations to provide routine self-report data for clinical and research applications. PMID- 8465679 TI - A sequential behavioral analysis of craving sweets in obese women. AB - This study compared 40 female participants in a behavioral weight loss program who frequently reported craving sweets to 40 who rarely reported craving sweets using 2-week behavioral eating diaries. The two groups were compared on physiological, demographic, and questionnaire measures and no significant differences were found. There were no significant differences in macronutrient intake either overall or in a wide range of specific situations. The relative proportions of carbohydrate, protein, and fat consumed in association with craving sweets differed only slightly from the composition of other meals and snacks. Carbohydrate and protein intake when craving sweets was similar to breakfasts while the relative amount of fat consumed when craving sweets was comparable to episodes of overeating. The two groups differed in their reporting of moods with the high-craving group reporting more boredom and less stress than the low-craving group. The relationship between situational and mood variables and reports of craving sweets did not differ between the two groups. Craving sweets was negatively associated with hunger and was not associated with meal skipping. A sequential analysis demonstrated that eating in response to craving sweets triggers an abstinence violation effect. These data are not consistent with the hypothesis that sweet craver's consume high-carbohydrate, low-protein meals and snacks in order to self-medicate depression caused by serotonin depletion. Instead, the data suggest that we should further explore the role of food palatability and food-related cognitions in order to understand craving sweets. PMID- 8465680 TI - Is there a general tendency to become addicted? AB - The tendency to become addicted across a number of different substances or activities was determined for a sample of 573 subjects, including college students and their parents. Four components of addiction were defined: craving, tolerance, withdrawal and lack of control. Subjects rated the extent to which each of these components characterized their relationships to each of ten substance/activities: coffee, tea, cola beverages, favorite alcoholic beverage, chocolate, nonchocolate sweets, hot chili pepper on food, cigarettes, gambling and video games. An "addiction score" was computed for each subject and each substance/activity, by summing the scores on the four components. Correlations in addiction scores for almost all activities were positive, but low (between 0 and .30), with the exception of chocolate and nonchocolate sweets, where the correlation was higher. The results suggest, at best, a weak tendency to become addicted, across a wide range of substances or activities. Other explanations for the low positive correlations are available, besides the notion of a general tendency to become addicted. There were a few significant mother-father correlations in various addiction scores, but none between mid-parent and child values. Three of the four components of addiction (craving, lack of control and withdrawal), were highly correlated. We conclude that there is little basis for the assumption of a general tendency to become addicted, a conclusion which casts doubt on the derivative notion of an addictive personality. PMID- 8465681 TI - Coping with dietary relapse crises and their aftermath. AB - We examined dieters' attempts to cope with dietary relapse crises (Immediate coping) and their aftermath (Restorative coping). We analyzed posttreatment interviews with 57 obese subjects with Type-II diabetes, comparing coping in situations in which subjects lapsed with those in which they survived temptations to overeat. Performance of Immediate coping predicted survival but the particular type of coping made little difference. Eight types of Immediate cognitive coping were equally associated with survival: each was significantly more effective than no coping and equal to the aggregate of the other types. A similar pattern held for 5 types of Immediate behavioral coping, except that social support was no more effective than no coping and restraint was less effective than the other types. Restorative behavioral coping was elicited as a response to overeating, while Restorative cognitive coping seemed elicited by the negative thoughts and feelings that sometimes accompany lapses or temptations. Implications for treatment and future research on relapse crises and coping are discussed. PMID- 8465682 TI - Social skills and depression in adolescent substance abusers. AB - The present study provided an assessment of social skills and depression in adolescent substance abusers hospitalized in an inpatient psychiatric setting. Level of social skill was evaluated using the Adolescent Assertion Expression Scale and the Loneliness Scale. Depression and related problems were examined through administration of the Beck Depression Inventory. Beck Hopelessness Scale, and the Rosenberg Self-Esteem Scale. Comparisons with normative values and clinical cut-offs (by gender) indicated that female adolescent substance abusers were less submissive and more aggressive than normative counterparts; male substance abusers exhibited less assertiveness. In addition, mild to moderate levels of depression were evident in both female and male substance abusers. Further, results of correlational analyses revealed several significant relationships between measures of social skills and depression. Results are discussed in terms of: (a) the need for finer grained analyses of social functioning in adolescent substance abusers, (b) the potential value of skills intervention for a subgroup of these individuals, and (c) the need for longitudinal data to more clearly explicate patterns and sequencing of social (mal)adjustment, affective disorder, and onset of substance abuse in this population. PMID- 8465683 TI - [Clinical use of an extracorporeal shock wave lithotriptor, Biolithos MARK III, for upper urinary tract stone]. AB - The results of clinical use of an extracorporeal shock wave lithotripter (Biolithos MARK III) are presented. From May 1991 through February 1992, a total of 50 sessions were carried out on 33 patients with upper urinary tract stones. Treatments were performed on an outpatient basis, and none of the patients needed anesthesia or analgesia. One month after the last session, 18 patients (54.5%) were free from stone fragments and 6 (18.2%) had stone fragments equal to or smaller than 4 mm. The over-all successful rate obtained by these categories was 72.7%. After treatment no serious complications were observed. Although gross hematuria appeared in almost all patients, pain was noted in only 5 patients. Laboratory data after treatments showed slight and transient changes. It is concluded that Biolithos MARK III is useful and safe in the management of upper urinary tract stones on an outpatient basis. PMID- 8465684 TI - [Clinical experience of percutaneous renal cyst puncture in recent six years]. AB - Ultrasound-guided renal cyst puncture of 69 renal cysts was performed in our department, between April, 1986 and March, 1992. The indications for this procedure consisted of cysts over 4 cm in diameter and those of less than 4 cm in diameter with caliceal or pelvic distortion and compression. Fifty-four cysts were instilled with dehydrated ethanol, 10 cysts with minocycline, one cyst with 50% dextrose as a sclerosing agent, and four cysts underwent only aspiration of the cyst fluid. We instilled dehydrated ethanol when the aspirated fluid was not bloody and there existed no extravasation of the contrast medium or communication between the cyst cavity and the urinary tract. The instilled volume of dehydrated ethanol ranged from 8 to 400 ml (average: 72.8 ml), equivalent to 35.0-100% (average: 62.1%) of the aspirated volume. Retention time was 20 minutes, the follow-up period was 2-67 months (mean follow-up period: 13.7 months), and the reduction rate of the cyst volume was 60.0-100% (average: 96.2%). There were no major complications due to puncture or dehydrated ethanol instillation. Ultrasound-guided renal cyst puncture was shown to be a safe non-surgical approach and a useful method of treating renal cysts. PMID- 8465685 TI - [Clinical significance of multiple mucosal biopsies in new cases of superficial papillary bladder tumor]. AB - We assessed the clinical significance of multiple mucosal biopsies in new cases of superficial papillary bladder tumor. Biopsy findings were abnormal (5 dysplasia, 5 transitional carcinoma) in 10 of the 71 cases examined. Abnormalities were observed exclusively at G2 or G3, and more frequently at pT1 than pTa. Cases with multiple tumors showed significantly more abnormalities than cases with a solitary tumor. Recurrence rates were not significantly different between the cases with abnormal biopsy findings and those with normal findings. However, the invasive tumor developed more frequently in the former. Mucosal biopsies seemed to be more useful in cases with multiple tumors than in those with a solitary tumor. PMID- 8465686 TI - [Clinical assessments on pre-treatment prognostic factors in 138 patients with advanced prostatic carcinoma (stage D2)]. AB - We investigated the prognostic factors in 138 patients with stage D2 prostatic cancer by univariate and multivariate analyses. Analysis was restricted to 8 pre treatment parameters, that is, age, general condition (PS), pain, number of metastases on bone scan, acid phosphatase value, Gleason's primary pattern, secondary pattern, and nucleoli grading. In addition, 4 therapeutic modalities except routine endocrine therapy, that is, castration, oral administration of estramustine phosphate, of 5-fluorouracil (5-FU) or its analogue, and combination chemotherapy, during the whole treatment period were included in the analysis. Univariate analysis (Kaplan-Meier method) showed only PS to be a significant prognostic factor. Multivariate analysis (Cox's proportional hazard model) revealed that PS, Gleason's primary pattern, oral administration of 5-FU or its analogue and combination chemotherapy were significant prognostic factors. However, patients treated by combination chemotherapy had poorer prognosis and chi 2 values of combination chemotherapy was the highest among the four parameters cited above. These results suggested that the 8 pre-treatment parameters examined in this study were not sufficient for predicting the prognosis of each patient. PMID- 8465687 TI - [Double inferior vena cava discovered by examination of traumatic rupture of congenital hydronephrotic renal pelvis: a case report]. AB - A case of double inferior vena cava associated with congenital hydronephrosis is reported. A 6-year-old girl was referred to our hospital with the chief complaint of severe left flank pain of sudden onset which occurred after she fell down some steps. Abdominal computerized tomographic (CT) scan revealed a huge perinephric urinoma, severe left hydronephrosis with obstructive atrophy and double inferior vena cava. Left nephrectomy was performed under a diagnosis of traumatic rupture of the left renal pelvis associated with left congenital hydronephrosis and double inferior vena cava. Rupture of the renal pelvis and ureteropelvic junction obstruction with severe parenchymal thinning were found. The postoperative course was uneventful. Double inferior vena cava is a relatively rare anomaly and most cases in recent years have been incidentally found by ultrasonography and CT scan. Urologists should keep in mind the possibility of this anomaly of the inferior vena cava, especially when reforming left nephrectomy. PMID- 8465688 TI - [A case of deoxycorticosterone-producing adrenal tumor]. AB - We present a case of a 11-deoxycorticosterone (DOC)-producing adrenocortical tumor. A 55-year-old female was admitted to our hospital with the chief complaints of sustained hypertension and weakness of lower extremities. A laboratory study revealed a decrease in the serum potassium level and plasma renin activity, a normal level of plasma aldosterone and a significant elevation of plasma DOC and 18-OH-DOC levels. The plasma DOC level was increased by ACTH stimulation and was not suppressed by dexamethasone. The tumor appeared at a low intensity of the T1 weighted image of magnetic resonance imaging (MRI) and at a high intensity on the T2 weighted image. Left adrenalectomy was performed and histological examination revealed a benign adrenal adenoma. Postoperatively, the abnormal blood pressure, serum potassium level and plasma level of DOC and 18-OH DOC became normal. PMID- 8465689 TI - [Idiopathic thrombocytopenic purpura (ITP) associated with renal injury: report of a case]. AB - A 42-year-old woman with gross hematuria, left flank pain and vomit after being hit on her back admitted to our hospital. She has been under treatment for idiopathic thrombocytopenic purpura (ITP) with prednisolone for these last 14 years. Computerized tomographic (CT) scan revealed moderate laceration, subcapsular hematoma and perirenal hematoma of the left kidney. We tried treating her conservatively. The main treatment was absolute rest for two weeks, increase in the prednisolone dose and prevention from infection. On the 3rd day, the platelet count dropped to 4,000/mm3, but transfusion of platelets was not done to provide for emergency. The platelet count increased gradually and returned to normal on the 8th day. We decreased the prednisolone dose according to the platelet count. After 5 weeks, microscopic hematuria disappeared. Her clinical course was uneventful and she was discharged after 7 weeks. PMID- 8465690 TI - [Renal cell carcinoma with contralateral adrenal metastasis: a case report]. AB - A case of contralateral adrenal metastasis of renal cell carcinoma is reported. The patient was a 54-year-old male, who underwent a right radical transperitoneal nephrectomy for renal cell carcinoma, and had been administered interferon alpha intramuscularly. Nine months after the operation computerized tomography revealed the presence of an adrenal mass on the left side, undetected at nephrectomy, which suggested that the renal cell carcinoma had metastasized. A left adrenalectomy was performed. Histologically, the mass was identical to metastasis of renal cell carcinoma. The patient was administered supplementary hydrocortisone and was well 3 months after the adrenalectomy with no evidence of recurrence or other metastasis. This is the 24th case of contralateral adrenal metastasis of renal cell carcinoma in the Japanese literature. PMID- 8465691 TI - A case of spontaneous recanalization following renal infarction. AB - A 30-year-old-male was admitted to our hospital with a tentative diagnosis of appendicitis. We found no signs of peritonitis, and therefore suspected urinary tract calculi. Intravenous pyelography revealed his right kidney to be nonfunctional, while retrograde pyelography was normal. Angiography revealed right renal infarction. Renovascular hypertension was present, and treatment with captopril was prescribed. Two years later without medication he had normal blood pressure and plasma renin activity. Intravenous pyelography revealed a right kidney functioning well, and digital subtraction angiography (DSA) revealed spontaneous recanalization of his right renal artery. PMID- 8465692 TI - [Multifocal renal oncocytoma: a case report]. AB - A case of multifocal renal oncocytoma in a 55-year-old man admitted for further examination following the detection of left renal tumors, is reported. Computerized tomographic (CT) scanning and magnetic resonance imaging (MRI) revealed 2 masses in the left kidney. A left radical nephrectomy was performed and two tumors were found. Both tumors were confirmed to be renal oncocytomas by light and electron microscopic examination. Including this patient, 42 cases of bilateral and multifocal renal oncocytoma have been reported in the literature to date. The clinical features of bilateral and multifocal renal oncocytomas are discussed accordingly. PMID- 8465693 TI - [Extracorporeal shock wave lithotripsy for ureteral stones which caused spontaneous peripelvic extravasation: report of three cases]. AB - We treated 3 cases of ureteral stones which caused spontaneous peripelvic extravasation by extracorporeal shock wave lithotripsy (ESWL). None had histories of trauma or operation. The obstructing stones measured 6 x 5, 6 x 5 and 4 x 3 mm respectively, and each was located in a left upper, right upper and right lower ureter. The drip infusion pyelography (DIP) and computerized tomography (CT) revealed a mildly dilated collecting system and ureter of affected site and extravasation of contrast material around the kidneys. These stones were successfully crushed and discharged by ESWL performed with an EDAP LT-01 device. One week after the last ESWL, the DIP showed favorable urograms and extinctions of extravasation. As ESWL could achieve a release of calculous obstruction easily with a safe and non-invasive procedure, we confirmed it to be an effective treatment for similar types of ureteral stones causing peripelvic extravasation. PMID- 8465694 TI - [Bilateral ectopic ureteroceles: a case report]. AB - The twelfth case of bilateral ectopic ureteroceles in Japan is reported. A two month-old girl was referred to our clinic because of urinary tract infection. Two large intravesical cystic lesions communicating to the dilated upper urinary tracts, which were compatible with bilateral ectopic ureteroceles were detected. Histological findings of the upper moieties of the duplex kidney showed dysplasia on the left side, and immaturity on the right side. Left heminephrectomy was performed, and a pyeloureterostomy was applied on the right side after placement of nephrostomy for 6 months. The ureteroceles collapsed satisfactorily to void smoothly. The patient has not been in trouble for more than thirty months postoperatively. Indications for preservation of the upper segment and ureterocelectomy in small infants are discussed. PMID- 8465695 TI - [Transurethral resection of papillary tumor in the lower end of the ureter: report of two cases]. AB - Two cases of papillary ureteral end tumors, treated by transurethral resection are presented. Case 1: A 71-year-old female visited us for asymptomatic macroscopic hematuria. Cystoscopy revealed a papillary pedunculated tumor in the bladder protruding from the right ureteral orifice. Under a diagnosis of superficial tumor at the right ureteral end, transurethral resection was performed using a rigid ureteral resectoscope. Pathological examination revealed transitional cell carcinoma, grade 2 without muscular invasion. There is no evidence of recurrence after 25 months of follow up postoperatively. Case 2: On a routine cystoscopy after transurethral resection of bladder tumor in a 68-year old male, papillary pedunculated tumors protruding from the right ureteral orifice were found. Under a diagnosis of superficial tumor at the right lower ureter, transurethral resection was performed using cold cup forceps and loop electrocoagulation. The tumor was transitional cell carcinoma, grade 1 without invasion. No evidence of recurrence was detected 15 months postoperatively. Transurethral resection of the ureteral tumor at the lower end appeared to be useful for the selected cases. The indications, complications and follow up for this procedure were discussed. PMID- 8465696 TI - [A case of genital tuberculosis occurring in the tunica albuginea and the tunica vaginalis]. AB - We report a case of genital tuberculosis occurring in the tunica albuginea and the tunica vaginalis. A 29-year-old man came to our department with the complaint of a nodule in the right scrotum. The physical and radiological examinations revealed no signs of pulmonary or urogenital tuberculosis. The urine and the semen were clear and negative in culture of acid fast bacteria, but the tuberculin reaction was moderately positive. Surgical exploration revealed a white yellowish soybean sized nodule in the surface of the tunica albuginea of the right testicle apart from the epididymidis, and we therefore enucleated it. No abnormalities were found in other parts of the tunica vaginalis, epididymidis or the funiculus. Histopathological examination demonstrated typical tuberculomas in the tunica albuginea and the tunica vaginalis, but the seminiferous tubules were almost intact. We diagnosed this case as tuberculosis arising in the tunica albuginea and the tunica vaginalis and started antituberculosis therapy. PMID- 8465697 TI - [A case of cholesterol granuloma with hematoma of tunica albuginea]. AB - A case of cholesterol granuloma with hematoma of the tunica albuginea is reported. A 52-year-old man complained of a painless mass in the left scrotum. The mass was 50 x 25 x 30 mm in size. An operation was performed. Macroscopically the mass originated from the tunica albuginea and was a cystic lesion with a thick fibrous capsule. The cystic lesion was filled with an old hematoma. An extirpation was performed. Microscopically, the sections showed fibrogranulomatous tissue containing innumerable cholesterol clefts and numerous foreign body giant cells. The histological diagnosis was cholesterol granuloma with hematoma. This is the sixth case of cholesterol granuloma of the external genitalia, and is the first case of cholesterol granuloma with hematoma of the tunica albuginea in the literature. PMID- 8465698 TI - [Clinical experience in extracorporeal shock wave lithotripsy with Sonolith 3000 for urinary stones]. AB - Extracorporeal shock wave lithotripsy (ESWL) using Sonolith 3000 was performed on 153 patients with urolithiasis form October, 1990 to April, 1992. The location of the stone was as follows; kidney in 70 cases, ureter in 82 cases and a Kock reservoir in one case. A double J catheter was installed in 6 cases before ESWL. Epidural anesthesia was required in 4 cases because of severe pain. Among 149 cases available for follow up one month after ESWL, 119 cases (79.9%) became stone free and 19 cases (12.8%) retained stone fragments less than 4 mm in diameter. The effectiveness rate, calculated as the sum of the cases stated above, was 92.7%. A side effect was observed in one case which was perirenal hematoma but required no therapy. PMID- 8465699 TI - The family physician and lumbar disk disease. PMID- 8465700 TI - Folic acid for the prevention of neural tube defects. PMID- 8465701 TI - Food irradiation: let's move ahead. PMID- 8465702 TI - L-epinephrine for croup: a new study. PMID- 8465703 TI - Cardiovascular complications of cocaine abuse. PMID- 8465704 TI - Fragile-X syndrome. PMID- 8465705 TI - Medical malpractice. PMID- 8465706 TI - Warfarin therapy. PMID- 8465707 TI - The shortage of generalist physicians. PMID- 8465709 TI - Diary of a week in practice. PMID- 8465708 TI - The shortage of generalist physicians. PMID- 8465710 TI - Lumbar disk disease: pathophysiology, management and prevention. AB - Patients with symptomatic lumbar disk disease may present with back pain, referred leg pain, radicular leg pain, sensory changes and leg weakness. Because neurologic deficits are commonly localized to the L5 or S1 nerve roots, evaluation of patients with such symptoms should focus on these dermatomes and muscle groups. Myelography, computed tomography, postmyelogram computed tomography and magnetic resonance imaging are the most valuable diagnostic studies. Initial management consists of physical therapy and reduced activity, followed by gradually increasing mobilization and exercise. Conservative treatment is effective for most patients. Surgical treatment is reserved for patients who have failed to improve with conservative therapy or those who present with a profound neurologic deficit. Prevention of recurrent symptoms centers on patient education and reassurance. A program of weight control, regular exercise and posture correction may reduce the frequency and severity of recurrent disk herniation and pain. PMID- 8465711 TI - Methylene chloride toxicity. AB - The effects of acute exposure to methylene chloride (dichloromethane) are due to its central nervous system depressant properties, which have resulted in fatalities. Manifestations of acute exposure include mental confusion, fatigue, lethargy, headache and chest pain. Metabolic conversion of methylene chloride to carbon monoxide may place persons with preexisting coronary artery disease at increased risk. Sequelae following chronic exposure are unknown, but data suggest serious long-term effects. The Environmental Protection Agency considers methylene chloride to be a probable human carcinogen. PMID- 8465712 TI - Alcoholic hepatitis. AB - Anorexia, weight loss, fatigue, symptoms of alcohol withdrawal and hepatomegaly are common early presenting signs and symptoms of alcohol abuse. The clinical diagnosis of alcoholic hepatitis can be made in alcoholics with associated fever, leukocytosis, jaundice and tender hepatomegaly. Associated laboratory abnormalities may include leukocytosis or leukopenia, anemia, a prolonged prothrombin time and elevated liver enzymes, including aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin. An AST-to-ALT ratio greater than 2 is common in patients with alcoholic hepatitis. Liver biopsy may be required to establish the diagnosis and to identify other pathology, such as cirrhosis. Histologic diagnosis of alcoholic hepatitis requires the presence of liver cell damage, an inflammatory infiltrate and fibrosis. Biopsy-proven cirrhosis with alcoholic hepatitis or a significantly elevated total bilirubin level and prolonged prothrombin time are associated with a worse prognosis. Abstinence from alcohol, nutritional supplementation and corticosteroids are the mainstays of treatment for severe alcoholic hepatitis. PMID- 8465713 TI - Treatment of obesity in the elderly. AB - Obesity is a common form of malnutrition among the elderly. Excessive weight gain is associated with decreased physical activity and a progressive decline in caloric requirements for weight maintenance. Obesity increases the risk of myocardial infarction, stroke, hypertension, noninsulin-dependent diabetes, osteoarthritis of the lower extremities and several types of cancer. Specific guidelines are recommended for weight-loss programs used in the elderly. While calories from dietary fats and carbohydrates are restricted, a protein intake of approximately 70 g per day is desirable. Exercise is an important part of the weight-loss program and contributes to a general sense of well-being. Limitation of motion may necessitate innovative forms of exercise for elderly patients. PMID- 8465714 TI - Neurocysticercosis. AB - Neurocysticercosis can be a cause of new-onset seizures. Cysticercosis is caused by fecal-oral spread of the parasite Taenia solium, the pork tapeworm, from affected individuals. Neurocysticercosis results from parasitic invasion of the central nervous system. The clinical presentation ranges from headaches to acute obstructive hydrocephalus. Computed tomography or magnetic resonance imaging is usually diagnostic, while serologic tests are generally less reliable. Treatment consists of praziquantel or albendazole, generally prescribed in combination with oral corticosteroids. PMID- 8465715 TI - Splenic artery aneurysms. AB - Splenic artery aneurysms are potentially life-threatening lesions with an uncertain propensity for serious consequences. These aneurysms are most often discovered incidentally in asymptomatic patients. Current practice standards suggest that definitive treatment should be undertaken in female patients in their childbearing years with lesions larger than 1 cm in diameter, in patients with lesions greater than 2 cm in diameter, in symptomatic patients and in patients with enlarging lesions. Patients with splenic artery aneurysms should be referred to vascular surgeons or vascular interventional radiologists for surgery or percutaneous embolization therapy. PMID- 8465716 TI - Pressure ulcers in nursing home patients. AB - Pressure, moisture, shear forces and friction lead to skin ulcer formation. Nursing home and home-bound patients with restricted mobility, poor nutrition, incontinence and chronic conditions such as anemia, diabetes and dementia are at risk for ulcer formation. Bedridden patients should be turned from side to side at 30-degree angles at least every two hours. Mattress and chair cushions, splints and cradle boots may reduce pressure. Good hygiene and barrier ointments, condom catheters, absorptive products and scheduled toileting for incontinence may control moisture. Calorie and protein supplements, feeding assistance and serial weight measurements are essential in the management of malnourished patients. Treatment should be based on the stage of the ulcer and the presence of conditions such as necrotic debris, infection and drainage. Saline wet-to-dry dressings and enzymatic and surgical debridement are necessary to remove necrotic tissue. Saline-soaked gauze, hydrogel preparations and occlusive dressings provide the physiologic environment for fibroblasts to grow and form granulation tissue. Patients with sepsis may require hospital admission for both further evaluation and systemic antibiotic therapy. PMID- 8465717 TI - Adverse effects of noise on hearing. AB - Excessive exposure to noise causes cells in the inner ear to degenerate and eventually can lead to permanent hearing loss. Although it has long been known that exposure to work-place noise can damage hearing, concern has recently been raised about hearing loss from excessive noise in recreational activities. The most effective way to decrease the incidence of noise-induced hearing loss is to educate people about the adverse health effects of excessive noise and to teach them how to protect their hearing. PMID- 8465718 TI - Asymptomatic bacteriuria in pregnancy. AB - Asymptomatic bacteriuria occurs in 4 to 7 percent of pregnancies and is associated with the development of acute pyelonephritis, preterm labor and low birth-weight infants. Treatment of bacteriuria prevents up to 80 percent of cases of pyelonephritis and reduces the risk of preterm delivery. All women should be screened for bacteriuria by a urine culture at the first prenatal visit. Women with bacteriuria should be treated with appropriate antibiotics and should be monitored throughout pregnancy to identify recurrences. Women with persistent bacteriuria require antibiotic suppression until delivery and urologic evaluation following delivery. Urologic evaluation during pregnancy is indicated if bacteriuria persists despite antibiotic therapy. PMID- 8465719 TI - Use of fluoroquinolones: practical considerations. AB - The fluoroquinolone class of antibiotics has expanded the therapeutic options available for serious bacterial infections. These antibiotics have activity against a wide variety of gram-negative organisms, including Pseudomonas aeruginosa, and selected gram-positive pathogens. Fluoroquinolones are well absorbed orally and are widely distributed into most tissues and fluids. Therapeutic indications include urinary tract infections, urethral and cervical gonorrhea, traveler's diarrhea, selected gram-negative respiratory and bone infections, and certain mycobacterial infections. Because adequate concentrations of fluoroquinolones are not achieved in cerebrospinal fluid, their use should be avoided in meningitis. Cost, drug interactions, adverse effects and resistance pose problems for the clinician. Fluoroquinolones should be restricted to proven indications when less costly agents are inappropriate. PMID- 8465720 TI - APA issues practice guidelines for eating disorders. PMID- 8465721 TI - AHA releases guidelines for CPR and emergency cardiac care. PMID- 8465722 TI - Lidocaine and dextran sulfate inhibit leukocyte accumulation but not postischemic contractile dysfunction in a canine model. AB - Leukocytes have been implicated as a possible factor in the pathogenesis of postischemic contractile dysfunction, probably through the release of oxygen free radicals. Lidocaine and dextran sulfate are known to inhibit leukocyte adherence to endothelial cells in vitro and in vivo. In an acute open-chest canine model both agents were found to inhibit the augmented accumulation of indium-111 labeled leukocytes in briefly ischemic and subsequently reperfused myocardium. Pharmacologic inhibition of leukocyte accumulation by lidocaine and dextran sulfate, however, was not associated with improvement in postischemic contractile dysfunction. PMID- 8465723 TI - Cardiac arrest and sudden unexpected death in variant angina: complications of coronary spasm that can occur in the absence of severe organic coronary stenosis. AB - Experiences in 81 patients with variant angina were reviewed with the goal of determining which clinical features were associated with the greatest risk of angina-linked cardiac arrest (13 patients) or sudden unexpected death (9 patients). The risk of occurrence of one of these actually or potentially fatal events was approximately tripled by the presence of either a history of angina linked syncope or documentation of serious arrhythmia complicating attacks. An unexpected finding was that the risk was increased 1.5-fold by the absence of high-grade organic coronary stenosis. Cardiac arrest and sudden death are important risks of variant angina, which can occur without the presence of severe organic coronary stenosis. These risks can be reduced by adequate vasodilator therapy that includes a calcium channel blocker. PMID- 8465724 TI - The effectiveness and safety of the simultaneous administration of quinidine and amiodarone in the conversion of chronic atrial fibrillation. AB - The effectiveness and safety of quinidine in the conversion of chronic atrial fibrillation after administration of amiodarone was assessed in 15 patients. A total quinidine dosage of 1097 +/- 408 mg was administered up the point of conversion or for a total of 48 hours. Nine of 15 patients (60%) converted to sinus rhythm. No clinical variable such as the duration of atrial fibrillation, left atrial size, left ventricular fractional shortening, amiodarone duration, or maintenance dose of amiodarone was able to discriminate between converters and nonconverters when patients were treated with the combination of amiodarone and quinidine. The mean QT interval with amiodarone was 414 +/- 44 msec and slightly increased to 434 +/- 40 msec (p = 0.01) when quinidine was added. The amiodarone quinidine combination was well tolerated, and no side effects or proarrhythmias were recorded. PMID- 8465725 TI - Radiofrequency versus pharmacologic modification of the atrioventricular node. AB - Although transcatheter radiofrequency modification of the atrioventricular (AV) node has been proposed as curative treatment in AV nodal reentry tachycardias, its role for the control of the ventricular rate in atrial tachyarrhythmias remains unclear. The aim of this study was to analyze the acute effect of radiofrequency current on AV nodal conduction and refractoriness, and to compare it with the effects of two antiarrhythmic drugs such as amiodarone (class III) and flecainide (class I). Twenty-one dogs were studied: (1) radiofrequency group (5 W for less than 45 seconds; 2 to 12 discharges; seven dogs); (2) amiodarone group (5 mg/kg intravenously; seven dogs); and (3) flecainide group (2 mg/kg intravenously; seven dogs). The following parameters were measured under basal conditions and after each procedure: AH interval, AV nodal functional refractory period, Wenckebach cycle length, minimum R-R interval during atrial fibrillation, and fitting of AV nodal function curve to a hyperbolic equation using its linear transformation. The AV nodal effective refractory period could not be calculated in any dog in the basal study because it was shorter than the atrial functional refractory period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465726 TI - Anterograde and retrograde decremental conduction over left-sided accessory atrioventricular pathways in the Wolff-Parkinson-White syndrome. AB - The electrophysiologic properties of left-sided accessory pathways (APs) were examined by cardiac stimulation in 55 patients with Wolff-Parkinson-White syndrome. Atrioventricular and ventriculoatrial conduction times were assessed at the coronary sinus level nearest to the AP and then plotted graphically as a function of coupling interval (for atrial and ventricular refractory period determinations). Of 29 patients with anterograde conduction over the AP, 10 (34%) exhibited decremental conduction. However, only two (7%) had a maximal decrement equal to or more than 30 msec. In the other eight (27%) patients the maximal decrement ranged from 10 to 20 msec. The longest coupling interval at which anterograde decremental conduction was demonstrated ranged from 260 to 440 msec (346 +/- 52 msec). The shortest coupling interval ranged from 240 to 320 msec (265 +/- 24 msec). The anterograde decremental conduction zone was 91 +/- 55 msec. Of 51 patients with retrograde conduction over the AP, 23 (45%) exhibited decremental conduction. However, only eight (15%) had a maximal decrement equal to or greater than 30 msec. In the other 15 (29%) patients the maximal decrement ranged from 10 to 25 msec. The longest coupling interval was 338 +/- 70 msec. The shortest coupling interval was 275 +/- 42 msec. The retrograde decremental conduction zone was 72 +/- 47 msec. There was a significant inverse correlation between the AP effective refractory period and the maximal decrement (r = -0.42; p < 0.05). The comparison of maximal ventriculoatrial conduction time with the maximal decrement revealed a positive correlation (r = 0.63; p < 0.01). These data reveal that minimal decremental conduction over left-sided APs is not an uncommon finding and stress that care should be taken in evaluation of conduction over these connections. PMID- 8465727 TI - Cardiac geometry and mass changes associated with pacing-induced cardiomyopathy in the dog. AB - We evaluated the effects of chronic rapid pacing (240 beats/min) on ventricular geometry and function and on cardiac mass in a canine model. Forty dogs were studied by two-dimensional echocardiography before and after 45 days of pacing. Compared with sham-operated control animals, the paced animals had significant increases in end-diastolic and end-systolic volume and a decrease in ejection fraction. The increase in ventricular volume was primarily the result of dilation of the short axis of the ventricular lumen, without significant changes in the long-axis dimension. Paced animals had biatrial hypertrophy but no change in ventricular or total cardiac mass. PMID- 8465728 TI - Velocity-encoded cine MRI in the evaluation of left ventricular diastolic function: measurement of mitral valve and pulmonary vein flow velocities and flow volume across the mitral valve. AB - Left ventricular diastolic function has been evaluated by means of analysis of the flow pattern through the mitral valve. Velocity-encoded cine magnetic resonance imaging (VEC-MR) is a new method for characterizing flow patterns in the heart. The feasibility of using VEC-MR to measure early diastolic (E) and atrial systolic (A) peak flow velocities and E/A ratios in the mitral inflow, as well as systolic (X), early diastolic (Y), and atrial systolic (Z) peak flow velocities and X/Y ratios in the pulmonary vein, was evaluated in 10 normal volunteers. The VEC-MR-derived velocities and indexes were compared with Doppler derived results. Volumetric flow across the mitral valve was also used to measure stroke volume, cardiac output, and the left atrial contribution of left ventricular filling. VEC-MR yielded lower peak velocities than Doppler echocardiography. The velocities of the two measurements showed a significant linear correlation (Doppler E velocity = 1.30 x VEC-MR + 1.6 cm/sec, r = 0.68; Doppler A velocity = 1.83 x VEC-MR - 5.2 cm/sec, r = 0.83; and Doppler X velocity = 0.45 x VEC-MR + 0.09 cm/sec, r = 0.74). Consequently the E/A and X/Y ratios measured by these two methods showed statistically significant linear correlations with r values of 0.94 and 0.83. The volume of blood flow across the mitral valve measured by VEC-MR (5610 +/- 620 ml/min) was not statistically different from the cardiac output measured from the ascending aorta by VEC-MR (5670 +/- 590 ml/min) or by left ventricular cine magnetic resonance imaging (5440 +/- 614 ml/min). The left atrial contribution to left ventricular filling was 25.9 +/- 7.5%. Our results indicate that VEC-MR can be used not only for evaluation of left ventricular diastolic filling from the mitral valve and pulmonary vein flow velocities but also for quantitative measurement of the volume of blood flow across the mitral valve. PMID- 8465729 TI - Echocardiographic and anatomic correlation of ventricular septal defect morphology in newborn Yucatan pigs. AB - With the use of a Yucatan micropig strain with a high incidence of ventricular septal defects (VSDs), results of two-dimensional and color-flow Doppler echocardiography of VSD morphology in newborn piglets were correlated with autopsy findings. A spectrum of perimembranous, muscular outlet, and doubly committed subarterial VSDs was found. Echocardiography was performed in 29 piglets weighing 1.2 to 4.4 (mean 2.8) kg, studied at age 4 to 18 (mean 8) days. VSD was diagnosed by means of echocardiography in 16 of 29 subjects; morphologic findings included perimembranous defects in 12, muscular outlet in two, and doubly committed subarterial defect in two. At autopsy the presence and location of defects were confirmed in all pigs. No additional defects were found. VSD diameters were 1.0 to 5.0 (mean 3.94) mm on echocardiography and 1.0 to 6.0 (mean 2.84) mm at autopsy. After aortic valve diameter was used as an internal control for tissue shrinkage during fixation, echocardiography/color Doppler imaging tended to overestimate VSD diameter by 21% (0.6 mm). In conclusion, echocardiography/Doppler imaging accurately identified the presence, morphology, and size of even the smallest VSDs in newborn Yucatan micropigs. Echocardiographic classification of VSD morphology in vivo will facilitate future research on specific types of VSDs in this animal model. PMID- 8465730 TI - Noninvasive evaluation of right ventricular and pulmonary artery systolic pressures in patients with ventricular septal defects: simultaneous study of Doppler and catheterization data. AB - The method for evaluating right ventricular and pulmonary artery systolic pressures by subtracting the systolic pressure gradient across the ventricular septal defect from the cuff systolic blood pressure is documented. To confirm the reliability and accuracy of this method, simultaneous continuous wave Doppler echocardiography and left and right cardiac catheterization were performed in 66 patients with congenital ventricular septal defects. The comparisons between the Doppler-derived right ventricular or pulmonary artery systolic pressures and those measured by catheterization yielded an excellent correlation (r = 0.969, y = 1.035x - 3.627, SEE = 8.2 mm Hg, p < 0.001 and r = 0.972, y = 1.012x - 2.904, SEE = 7.6 mm Hg, p < 0.001), respectively. There was a close agreement between the Doppler-derived right ventricular or pulmonary artery systolic pressures and those measured by catheters, and the differences between the two measurements did not differ significantly from zero. It is concluded that Doppler echocardiography offers a reliable and accurate method for noninvasive assessment of right ventricular and pulmonary artery systolic pressures in patients with ventricular septal defects. PMID- 8465731 TI - Quantification of aortic regurgitation by magnetic resonance velocity mapping. AB - The use of magnetic resonance (MR) velocity mapping in the quantification of aortic valvular blood flow was examined in 10 patients with angiographically verified aortic regurgitation. MR velocity mapping succeeded in identifying and quantifying the regurgitation in all patients, and the regurgitant volume determined with MR velocity mapping agreed well with the grade obtained by aortic root angiography (p < 0.02). The accuracy in quantification of the aortic valvular flow rate was demonstrated by a significant correlation between the stroke volume (ml) measured by MR velocity mapping and calculated from MR imaging of the left ventricular end-diastolic and end-systolic volumes in eight patients (Y = 0.89 x X + 11, r = 0.97, p < 0.001). This finding was confirmed by a good agreement between the net cardiac output (L/min) quantified with MR velocity mapping and simultaneous 125I-indicator dilution measurement in all subjects (Y = 0.89 x X + 0.08, r = 0.82, p < 0.01). In conclusion, MR velocity mapping may be used as a noninvasive tool in the quantification of aortic regurgitation. PMID- 8465732 TI - Immediate and long-term results of balloon and surgical closed mitral valvotomy: a randomized comparative study. AB - Balloon mitral valvotomy (BMV) constitutes an important alternative to surgical closed mitral valvotomy (CMV) for the treatment of rheumatic mitral stenosis. To compare the immediate and long-term results of these procedures, 200 patients with rheumatic mitral stenosis were randomly assigned to undergo either BMV (n = 100) or CMV (n = 100). The age range was 10 to 30 (mean 19.4 +/- 6.5) years. Both procedures resulted in significant and similar increases in mitral valve area (BMV: 0.85 +/- 0.26 to 2.39 +/- 0.94 cm2; CMV: 0.79 +/- 0.21 to 2.2 +/- 0.85 cm2; p = NS). Mitral regurgitation developed in 14 patients after BMV and in 12 patients after CMV. Eighty patients in each group have now been followed for a mean period of 22 +/- 6.3 (range 6 to 38) months by repeat echocardiographic study. Restenosis (defined as a loss of more than 50% of the achieved increase in mitral valve area) was seen in four (5%) patients after BMV and in three (4%) after CMV. Symptomatic restenosis was seen in only one patient who at follow-up examination 20 months after CMV had a mitral valve area of 0.8 cm2 and underwent successful balloon valvotomy. We conclude that the immediate and long-term results obtained with percutaneous BMV and surgical closed mitral commissurotomy are comparable. PMID- 8465733 TI - The comparative value of transesophageal and transthoracic echocardiography before and after percutaneous mitral balloon valvotomy: a prospective study. AB - Transthoracic (TTE) and transesophageal echocardiography (TEE) were performed prospectively on 53 consecutive patients (mean age 59 +/- 14 years) immediately before and within 24 hours of mitral balloon valvotomy to compare the relative value of the two techniques. Biplane TEE was used in 38 patients and single-plane imaging was done in 11. All patients underwent left and right cardiac catheterization, left ventriculography, and coronary angiography. While TEE provided excellent images of the mitral valve in all patients, imaging planes were more limited than by TTE. Mitral valve morphology could be assessed satisfactorily by either technique. Echo scores derived from each showed good correlation (r = 0.90, p < 0.001). TEE transgastric longitudinal scanning provided superior detail of the subvalvar apparatus but only in 20 (53%) of 38 patients. Patients with good transgastric views had significantly smaller left atrial volumes than those without (58 +/- 22 vs 106 +/- 41 cm3, p < 0.001). Mitral valve orifice and the commissures were better assessed by TTE. Before valvotomy, mitral regurgitation (MR) graded by TEE and TTE color flow mapping was concordant with angiography in 80% and 81%, respectively. After valvotomy, TTE color flow mapping failed to detect MR in two of the three patients who developed severe MR. Two of these patients were examined by TEE, which demonstrated both the MR jets as well as leaflet tears. Thrombus was diagnosed in the left atrium in eight patients by TEE and in only one patient by TTE. Biplane TEE was required for accurate thrombus localization and for assessing its size and extent. Five patients with thrombus underwent balloon valvotomy without complications. Left-to right atrial shunting was detected by TEE and TTE in 95% and 48% of patients, respectively. Flow convergence regions, from which quantitative flow information can be derived, were imaged by TEE only. TTE and TEE have complementary roles. However, TEE is essential for excluding thrombus in the left atrium before balloon valvotomy. After the procedure, TEE is recommended for the evaluation of patients with severe mitral regurgitation. PMID- 8465734 TI - Percutaneous balloon mitral valvotomy in pregnant patients with tight pliable mitral stenosis. AB - Percutaneous balloon mitral valvotomy was attempted in severely symptomatic (New York Heart Association class III or IV) pregnant patients (mean age 30 years) with tight mitral stenosis. Nineteen patients were pregnant (mean gestation 30 weeks, range 26 to 34) and one patient was in the immediate postpartum period. All patients had undergone a trial of diuretic therapy and 16 were also taking atenolol. Percutaneous valvotomy was performed with the Inoue catheter (18 patients) or the Schneider-Medintag bifoil (2 x 19 mm) balloon catheter (2 patients). The fluoroscopy time was 9.2 +/- 3.4 minutes. After percutaneous valvotomy the mean mitral gradient decreased from 17.9 +/- 6.2 to 5.9 +/- 2.4 mm Hg (p < 0.001). The mitral valve area (pressure half time) increased from 0.8 +/- 0.2 to 1.7 +/- 0.2 cm2 (p < 0.001). These hemodynamic changes were accompanied by immediate symptomatic improvement by at least one New York Heart Association functional grade in all patients. Moderate (3+) mitral regurgitation developed in one patient. Eighteen patients had normal infants delivered vaginally at term without assistance, and one patient had a normal infant delivered by cesarean section at 35 weeks' gestation. We conclude that percutaneous balloon mitral valvotomy for pliable mitral stenosis in pregnancy is safe for both the mother and fetus. We recommend that it be performed in symptomatic patients with tight mitral stenosis so as to avoid hemodynamic complications in the latter stages of pregnancy. PMID- 8465735 TI - Pulmonary artery pressure and pulmonary vascular resistance before and after mitral balloon valvotomy in 100 patients with severe mitral valve stenosis. AB - We studied the pulmonary vascular hemodynamics before and after mitral balloon valvotomy in 100 patients with severe mitral valve stenosis. Before balloon valvotomy 23 patients had a pulmonary artery systolic pressure of < 31 mm Hg (group 1), 54 patients had a pulmonary artery systolic pressure between 31 and 50 mm Hg (group 2), and 23 patients had a pulmonary artery systolic pressure of > 50 mm Hg (group 3). After balloon valvotomy the mean systolic pulmonary artery pressure in group 1 decreased from 28 +/- 3 to 26 +/- 5 mm Hg (p = NS). In group 2 the systolic pulmonary artery pressure after balloon valvotomy decreased from 41 +/- 5 to 33 +/- 7 mm Hg (p < 0.0001) and normalized to < 31mm Hg in 27 patients (50%). The mean left atrial pressure was abnormal (> or = 13 mm Hg) in 6 of 27 patients (22%) who had a systolic pulmonary artery systolic pressure of < 31 mm Hg and in 6 of 27 patients (22%) with a pulmonary artery systolic pressure of > or = 31 mm Hg. The pulmonary vascular resistance was abnormal in 36 of 54 patients (67%) after mitral balloon valvotomy; only 5 of 36 patients (14%) had a raised left atrial pressure (> or = 13 mm Hg). In group 3 the pulmonary vascular resistance was abnormal (> 125 dynes/sec/cm-5) in all 23 patients before and in 19 of 31 patients (91%) after balloon valvotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465736 TI - Medical complications of cocaine: possible relationship to low plasma cholinesterase enzyme. AB - What predisposes some cocaine users to its complications is not known. Because cocaine is metabolized by plasma cholinesterase enzyme, we evaluated this enzyme in 14 patients with cocaine-induced complications, 11 long-term cocaine users from Bolivia, 14 persons in the United States without any documented cocaine induced complications, and 14 subjects who have not used cocaine. The enzyme was found to be significantly lower in patients with cocaine-induced complications as compared to other groups (p < 0.05). A low level of plasma cholinesterase enzyme may predict complications from cocaine use. PMID- 8465737 TI - The left ventricle in systemic lupus erythematosus: initial observations and a five-year follow-up in a university medical center population. AB - The objectives of this study were to determine the natural history of abnormalities in left ventricular size and function in patients with systemic lupus erythematosus and to determine whether changes in ventricular function can be attributed to a primary lupus cardiomyopathy. The design was a prospective 5 year follow-up study in a university hospital. There were 28 patients with systemic lupus erythematosis who were enrolled in an echocardiographic study from 1985 to 1986 and who were available for follow-up echocardiographic examinations. Patients were prospectively subgrouped according to the presence or absence of systemic hypertension. Twenty healthy volunteers participated as normal control subjects. Measurements of left ventricular mass index, mean wall thickness, volumes, and ejection fraction and Doppler indices of mitral inflow were performed on all patients and control subjects. Increases in left ventricular mass index, mean wall thickness, and end-systolic volume and decreases in ejection fraction were seen in the patients with lupus when compared with control subjects (p < or = 0.05) and were related to the presence of hypertension and coronary artery disease. In the group of patients without hypertension, no significant differences in left ventricular mass index, volumes, or ejection fraction were detected when compared with the control group. The normotensive patients did demonstrate mild abnormalities of mitral inflow that did not worsen during the follow-up period. It was concluded that abnormalities of systolic and diastolic left ventricular function are common in patients with lupus, are progressive over time, and are related to the coexistence of hypertension and coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465738 TI - A comparison of cardiac valvular involvement in the primary antiphospholipid syndrome versus anticardiolipin-negative systemic lupus erythematosus. AB - Recurrent thrombosis and pregnancy loss are well-recognized features of the antiphospholipid syndrome. Uncertainty exists, however, as to whether other reported features of the antiphospholipid syndrome such as cardiac valvular vegetations are truly part of this disorder or more reflective of associated systemic lupus erythematosus (SLE). Several recent studies have concluded that patients with antiphospholipid antibodies have a higher risk of developing Libman Sacks endocarditis. This study was performed to determine whether antiphospholipid antibodies are the only risk factors for cardiac valvular disease in patients with primary antiphospholipid syndrome (PAPS) or SLE. Ten patients with PAPS were matched with 20 patients with SLE and 20 healthy control subjects by sex. All participants were tested for anticardiolipin (aCL) antibodies by means of a standardized enzyme-linked immunosorbent assay technique, and all underwent two-dimensional and color-flow Doppler echocardiography. The echocardiograms were interpreted by two cardiologists blinded to the patients' underlying disease. Sixty percent of the PAPS group had cardiac valvular involvement compared with 40% of the SLE group (p = NS). We conclude that cardiac valvular vegetations are common both in aCL-negative patients with SLE and in patients with PAPS. This suggests that aCL antibodies either play no causative role or are not the only risk factors in the development of cardiac valvular vegetations. PMID- 8465739 TI - Identification of high-risk patients with left main and three-vessel coronary artery disease by adenosine-single photon emission computed tomographic thallium imaging. AB - The purpose of this study was to examine the ability of SPECT imaging with thallium-201 during adenosine-induced coronary hyperemia to detect high-risk patients with left main or three-vessel CAD. There were 339 patients: 102 with either left main or three-vessel CAD (group 1) and 237 with no CAD, one-, or two vessel disease (group 2). By means of univariate analysis, several variables were found to differ between groups 1 and 2: Q wave myocardial infarction (35% vs 25%, p < 0.05), ST segment depression (35% vs 19%, p < 0.001), age (67 +/- 9 vs 62 +/- 10 years, p < 0.001), resting systolic blood pressure (142 +/- 22 vs 135 +/- 20 mm Hg, p < 0.01), abnormal thallium images (95% vs 74%, p < 0.0001), multivessel thallium abnormality (76% vs 39%, p < 0.0001), extent of thallium abnormality (24 +/- 11% vs 19 +/- 13%, p < 0.0001), and increased lung thallium uptake (39% vs 15%, p < 0.01). According to stepwise discriminant analysis, only three variables were predictors of high risk: multivessel thallium abnormality (chi 2 = 27), increased lung thallium uptake (chi 2 = 10), and ST depression (chi 2 = 5). On the basis of these variables, patients were divided into three groups with different prevalence rates for left main and three-vessel CAD: 63% in 68 patients, 30% in 137 patients, and 13% in 137 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465740 TI - The diagnostic utility of contrast echocardiography in patients with refractory hypoxemia. AB - Three illustrative cases of refractory hypoxemia in adults are presented. In two cases contrast echocardiography was invaluable in establishing the diagnosis of a true anatomic right to left shunt, as well as in localizing the shunt to an intracardiac or extracardiac site. In the third case true anatomic right to left shunt was excluded by means of contrast echocardiography. The pathophysiology of hypoxemia is discussed with emphasis on the potential diagnostic utility of contrast echocardiology in patients with refractory hypoxemia. A diagnostic flow chart is proposed. PMID- 8465741 TI - Platelet and neutrophil imaging techniques in the investigation of the response to thrombolytic therapy and the no-reflow phenomenon. PMID- 8465742 TI - Influence of heart rate on mortality among persons with hypertension: the Framingham Study. AB - Previous studies have shown positive associations between heart rate and both all cause and cardiovascular mortality. These relationships, however, have not been investigated in persons with hypertension. Using 36-year follow-up data from the Framingham Study, we evaluated from 4530 subjects, aged 35 to 74, whose blood pressures were > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic and who were not treated with antihypertensive medication. We used pooled logistic regression to calculate biennial mortality rates. Odds ratios and 95% confidence intervals for each increment in heart rate of 40 beats/min, adjusted for age and systolic blood pressure level, were: for all-cause mortality, 2.18 (1.68, 2.83) for men and 2.14 (1.59, 2.88) for women; and for cardiovascular mortality, 1.68 (1.19, 2.37) for men and 1.70 (1.08, 2.67) for women. Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness. Therefore heart rate may be an independent risk factor for cardiovascular death in persons with hypertension. PMID- 8465743 TI - Secular blood pressure trends in normotensive persons: the Framingham Study. AB - Trends in hypertension prevalence are difficult to assess because of a massive increase in the prevalence of antihypertensive treatment. Over the past three decades mean blood pressure levels among the 5209 members of the Framingham Study cohort have declined, and elevated blood pressure is only one third as prevalent. However, if those receiving treatment who have normalized blood pressures are defined as hypertensive, in addition to those with elevated blood pressure, the prevalence of hypertension has increased. No consistent secular trend in the incidence of hypertension was noted over three decades, but high blood pressure eventually developed in two thirds of the study cohort. To determine whether untreated blood pressure levels are changing over time, trends in mean blood pressure were examined in normotensive subjects over three decades. Only a 1 mm Hg decline in mean systolic and diastolic pressure over each 10-year interval was noted (p < 0.001). Thus blood pressure in the normotensive segment of the population has been quite stable. Because the incidence of hypertension is very high and future hypertension arises from the upper end of the normal blood pressure distribution, there is an urgent need for primary prevention. Preventive measures such as exercise, avoidance of salt and alcohol, and especially weight control deserve a high priority. PMID- 8465744 TI - Monitoring cyclical coronary blood flow alterations after coronary angioplasty for stent restenosis with a Doppler guide wire. PMID- 8465745 TI - Emergent saphenous vein graft stent after unsuccessful balloon angioplasty: clinical, angiographic, and histologic findings. PMID- 8465746 TI - Coronary angioplasty of radiation-induced stenosis. PMID- 8465747 TI - Coronary steal through a patent internal mammary artery graft: treatment by subclavian angioplasty. PMID- 8465748 TI - Revascularization in fibromuscular dysplasia of the coronary arteries. PMID- 8465749 TI - The combined presence of myocardial bridging and fixed coronary artery stenosis. PMID- 8465750 TI - Coronary atherectomy complicated by coronary embolus in a cardiac transplant recipient. PMID- 8465751 TI - Analysis of VNTR loci amplified by the polymerase chain reaction for investigating the origin of intimal smooth muscle cells in a coronary artery lesion developing after heart transplantation in man. PMID- 8465752 TI - Morbidity of endomyocardial biopsy in cardiac transplant recipients. PMID- 8465753 TI - Fatal aortic rupture during balloon dilatation of recoarctation. PMID- 8465754 TI - Complete heart block after percutaneous Inoue balloon mitral valvotomy. PMID- 8465755 TI - Ruptured congenital aneurysm of the sinus of Valsalva with persistent left superior vena cava imaged by intraoperative transesophageal echocardiography. PMID- 8465756 TI - Critical discrete subaortic stenosis in the newborn period. PMID- 8465757 TI - Transesophageal echocardiographic diagnosis of a primary intraaortic tumor. PMID- 8465758 TI - Endarteritis associated with a clinically silent patent ductus arteriosus. PMID- 8465759 TI - Effusive constrictive epicarditis and atrial septal defect. PMID- 8465760 TI - Medical management of prosthetic aortic valve endocarditis and aortic root abscess. PMID- 8465761 TI - Ventricular tachycardia with retrograde 2:1 atrial activation masquerading as T wave alternans. PMID- 8465762 TI - Accelerated secretion of atrial natriuretic peptide during exercise in effort angina. PMID- 8465763 TI - Central precordial reciprocal ST-segment elevation in posterolateral myocardial infarction. PMID- 8465764 TI - Aortic rupture after balloon angioplasty of aortic coarctation. PMID- 8465765 TI - Emergency coronary angioplasty for acute myocardial infarction: predictors of early occlusion of the infarct-related artery after balloon inflation. AB - THE FACTORS RESPONSIBLE FOR EARLY OCCLUSION OF THE INFARCT VESSEL AFTER emergency percutaneous transluminal coronary angioplasty (PTCA) were retrospectively examined in 191 patients with acute myocardial infarction. During the 24-hour period after the initial balloon inflation, 47 patients (25%) had occlusion of the vessel (occlusion group), whereas 144 did not (nonocclusion group). The former patients immediately underwent repeat PTCA, which was successful in 37. Univariate correlates of early occlusion were a shorter time interval between the onset of symptoms and PTCA (3.5 +/- 2.2 vs 4.5 +/- 2.9 hours, p = 0.025), right coronary artery involvement (53% vs 30%, p = 0.015), prior thrombolytic therapy (49% vs 32%, p = 0.035), and undersized inflation (43% vs 17%, p < 0.001). With multivariate analysis the three independent predictors were undersized inflation (p < 0.001), right coronary artery involvement (p = 0.004), and a shorter time interval until PTCA (p = 0.011). Thus patients undergoing early PTCA and having right coronary artery involvement appear to be at greater risk of having early occlusion. Thrombolytic agents and undersized inflation may also play an important role in its development. PMID- 8465766 TI - Functional recovery after reperfusion is predicated on recovery of myocardial oxidative metabolism. AB - To test the hypothesis that recovery of myocardial oxidative metabolism (MVO2) is a necessary prerequisite for recovery of contractile function following reperfusion and to evaluate its dependency on the interval of antecedent ischemia before reflow, we evaluated 11 dogs serially for 4 weeks. Six dogs were subjected to prompt reperfusion (after 1 hour of coronary artery occlusion) and five were subjected to delayed reperfusion (after 4 hours of ischemia). Despite equivalent levels of myocardial blood flow with reperfusion, hearts subjected to prompt reperfusion had faster and more complete recovery of MVO2 (assessed by sequential positron emission tomography with [11C]acetate) and function (assessed by echocardiography) compared with dogs subjected to delayed reperfusion. Infarct size was diminished in dogs with prompt reperfusion. In all dogs, recovery of function with reperfusion was predicted and correlated with early recovery of MVO2 (r = 0.61, p < 0.04). The results demonstrate that prompt reperfusion is associated with more rapid and complete recovery of oxidative metabolism and function and support the hypothesis that the ability to metabolize substrate oxidatively is a necessary prerequisite for recovery of function. PMID- 8465767 TI - Prediction of single and multivessel coronary disease in patients after myocardial infarction according to quantitative ultrasound wall-motion analysis. AB - Regional changes in left ventricular size and function characterize left ventricular remodeling and start very early after myocardial infarction. We studied the diagnostic value of left ventricular dyssynergic patterns in predicting the presence of single versus multivessel disease (MVD). Fifty-three consecutive patients with acute myocardial infarction were studied by ECG, two dimensional echocardiography, and angiography during the same hospitalization. Thirty-eight normal subjects served as the control group. According to the angiographic findings, the patients were categorized as having: single-vessel disease (SVD, n = 17), two-vessel disease (n = 17), and three-vessel disease (n = 19). Two-dimensional echocardiography was performed and optimal frames from five cardiac cycles were digitized and quantitatively analyzed off-line with a microcomputer. Echocardiographic wall-motion analysis demonstrated a depressed regional segmental thickening in the infarcted area that was characteristic for each echocardiographic view. In the segments remote from the infarcted area, however, the three patient groups displayed differences in function that ranged from hyperkinetic in patients with SVD to hypokinetic in patients with MVD. Patients with SVD constantly displayed a wider range of segmental thickening when compared with patients with MVD and the control group (p < 0.05). In conclusion, patients with SVD after myocardial infarction display compensatory hyperkinesis of remote segments, which is attenuated in patients with MVD. The present study introduces new parameters of segmental myocardial function that might be helpful in predicting SVD and MVD in patients after myocardial infarction. PMID- 8465768 TI - Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E. AB - We investigated the effects of a high-cholesterol diet in the presence and absence of vitamin E on the lipid peroxidation product malondialdehyde of blood and aortic tissue, the oxygen-free-radical-producing activity of polymorphonuclear leukocytes (PMNs) (PMN chemiluminescence), and the blood lipid profile in rabbits. The animals were divided into four groups each of which comprised 10 rabbits. Rabbits in group I received a regular rabbit chow diet; those in group II received vitamin E; those in group III received high cholesterol + vitamin E; and those in group IV received a high-cholesterol diet. Blood concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), malondialdehyde, and PMN chemiluminescence were measured. The aorta of each rabbit was removed at the end of the protocol for assessment of atherosclerotic changes (gross and microscopic) and malondialdehyde. Serum triglycerides, total cholesterol, HDL-C, LDL-C, and VLDL-C increased while HDL/LDL ratio decreased in groups III and IV but remained unchanged in group I. There was an increase in the HDL-C component and HDL/LDL ratio and a decrease in the LDL-C component and triglycerides in group II. Blood and aortic tissue malondialdehyde increased in group IV but decreased in groups II and III. PMN chemiluminescence increased in groups III and IV. Atherosclerotic changes were marked in group IV as compared with those in group III. However, histologic changes in the aortas were similar in groups III and IV. The increased levels of blood and aortic tissue malondialdehyde and PMN chemiluminescence, which were associated with development of atherosclerosis, suggest a role of oxygen free radicals in the pathogenesis of hypercholesterolemia-induced atherosclerosis. The protection afforded by vitamin E, which was associated with a decrease in blood and aortic tissue malondialdehyde concentration in spite of hypercholesterolemia, supports the hypothesis that oxygen free radicals are involved in the development of hypercholesterolemic atherosclerosis. PMID- 8465769 TI - Lipid peroxides and antioxidant defenses in accelerated transplantation associated coronary arteriosclerosis. AB - Accelerated coronary artery disease develops in most if not all heart transplant recipients within the first year after transplantation. Increased lipid peroxidation seems to be involved in atherogenesis. In these patients we have investigated whether there is an association between lipid peroxidation, reduced antioxidant defenses, and some conventional coronary risk factors. Lipid peroxides, lipids, uric acid, albumin, antioxidant enzymes and their cofactors (the trace elements selenium, iron, copper, and zinc) have been determined in heart transplant recipients compared with nonrecipients with coronary artery disease. Lipid peroxides (p = 0.002) and uric acid (p = 0.01) were higher and zinc (p = 0.001) was lower in heart transplant recipients. Thirteen of 30 transplant recipients compared with one of 30 nonrecipients (p < 0.001) had very low (less than 10 mumol/L) zinc levels. Antioxidant enzymes and other trace elements were not significantly different. In univariate regression analysis, zinc correlated positively with albumin (p = 0.02) and negatively with lipid peroxides (p < 0.05). Uricemia had a strongly positive correlation with hydroperoxides (r = 0.45; p = 0.0001). In stepwise multivariate regression analysis, lipids, uricemia, creatinine, and zinc were significant (p < or = 0.004) predictors of the lipid peroxide level. Cyclosporine and corticosteroid dosages were significant (p = 0.01) determinants of zinc concentration in the transplant recipients. Although a causal relationship between increased lipid peroxidation and accelerated arteriosclerosis is not definitely demonstrated, the results of this analysis suggest new insights into conventional coronary disease risk factors and possible therapeutic interventions; further controlled trials are needed. PMID- 8465770 TI - Transient terminal U wave inversion as a more specific marker for myocardial ischemia. AB - Transient U wave inversion can be caused either by regional myocardial ischemia or by an elevation of systemic blood pressure. The characteristics of U wave inversion during chest pain attacks in 21 patients with variant angina were compared with those observed in 38 patients with hypertension without apparent ischemic heart disease. Differentiation was possible according to the ECG phase in which U wave inversion appeared. U wave inversion was considered to be significant if there was a discrete negative deflection of more than 0.05 mV within the TP segment. U wave inversion proceeded to positive deflection of U wave in patients with hypertension without ischemic heart disease (initial U wave inversion). In contrast, inverted U wave occurred after positive U wave deflection during attacks in patients with variant angina (terminal U wave inversion). When cold pressor test was performed in patients with variant angina during treatment with calcium entry blockers, no patient had either anginal attacks or ischemic ST-segment deviation, but 9 of 21 patients (43%) had transient initial U wave inversion, which was followed by positive U wave deflection. U wave inversion can be classified as initial U wave inversion and terminal U wave inversion according to the phasic relationship to positive U wave deflection; the latter is observed in association with regional myocardial ischemia. The former seems to be related to elevated blood pressure rather than to myocardial ischemia. PMID- 8465771 TI - Protective effect of coronary sinus obstruction from primary ischemia-induced ventricular fibrillation in the dog. AB - We examined whether partial coronary sinus obstruction affects the latency of the early ventricular fibrillation (VF) of acute ischemia. During baseline trials 15 of 19 open-chest dogs fibrillated repeatedly and predictably within 2 to 5 minutes (251.6 +/- 64 seconds) after reversible, double coronary artery occlusion without developing profound hemodynamic deterioration. The effect of partial coronary sinus obstruction sufficient to increase coronary sinus pressure to 40 mm Hg could be adequately tested in 11 dogs. Coronary sinus obstruction consistently prevented VF in five dogs, significantly prolonged the VF latency in three (p < 0.01 to p < 0.001), and had no clear effect in another three. The overall effect was significant at the p < 0.01 level. VF latency prolongation/prevention was also positively correlated to the residual coronary sinus pressure at the time of VF (r = 0.76; p < 0.008), as well as the baseline VF latency (r = 0.75; (p < 0.008). The protective effect of coronary venous hypertension most likely reflects preservation of adequate extracellular fluid in the ischemic region after the perfusion arrest. This extracellular fluid may constitute a key component in the prevention of early ischemic arrhythmias by preserving interstitial hydraulic continuity and tissue homogeneity through enhanced dilution and diffusion of solutes. PMID- 8465772 TI - Additional antianginal efficacy of amiodarone in patients with limiting angina pectoris. AB - Sixty-three patients with stable angina New York Heart Association (NYHA) class III and a positive stress test despite triple therapy were randomized to a double blind protocol, receiving either placebo or amiodarone in a dose of 600 mg/day for 10 days, followed by 400 mg/day for an additional 10 days, and then by 200 mg/day over a total period of 2 months. Comparable bicycle exercise times were observed at baseline in the amiodarone group (6.0 +/- 1.6 minutes) and in the placebo group (6.0 +/- 1.8 minutes). With amiodarone, there was a increase in exercise duration of 6.7 +/- 2.2 minutes versus 6.3 +/- 2.2 minutes at 1 month and 7.5 +/- 2.1 minutes versus 6.2 +/- 1.7 minutes at 2 months (p < 0.05). Also, the amiodarone group had a significant decrease in the double product when compared with the placebo group at 1 month (14,134 +/- 3,316 versus 17,570 +/- 4,092 mm Hg/min, p < 0.001) and at 2 months (14,022 +/- 3,303 and 17,298 +/- 4,872 mm Hg/min, p < 0.001). The degree of ST segment depression at peak exercise was also significantly reduced. Combination therapy of amiodarone with conventional antianginal therapy is well tolerated and results in a significant improvement in exercise capacity and a mild reduction of symptoms in patients who have continued, limiting angina pectoris with conventional triple therapy. PMID- 8465773 TI - Three-dimensional transesophageal echo imaging of the descending thoracic aorta. PMID- 8465774 TI - Exercise responses after cardiac transplantation in mitochondrial myopathy. PMID- 8465775 TI - Exercise hyperventilation chronic congestive heart failure and its relation to functional capacity and hemodynamics. PMID- 8465776 TI - More on death in the opera. PMID- 8465777 TI - Usefulness of myocardial contrast echocardiography in detecting the immediate changes in anterograde blood flow reserve after coronary angioplasty. AB - Myocardial contrast echocardiography has revealed that successful coronary angioplasty results in an immediate decrease in the amount of collateral blood flow to the perfusion bed supplied by the dilated vessel. This information could potentially be used with pharmacologic stress in the catheterization laboratory to also assess the improvement in coronary flow reserve after angioplasty. The immediate changes in area under the time intensity curve produced by a 1 ml slow injection of sonicated albumin immediately proximal to a stenosis before and after 14 angiographically successful angioplasties was studied in 12 patients. Area under the curve was assessed before and after an 8 mg selective injection of papaverine. The changes in area under the curve were correlated with percent improvement in epicardial area stenosis. Visually successful angioplasty resulted in > 30% improvement in area under the curve after papaverine in 9 of 14 studies. There was a significant correlation between improvement in area under the curve after papaverine and percent improvement in epicardial area stenosis (r = 0.75; p < 0.01). No patient had left ventricular wall motion abnormalities after papaverine before or after angioplasty. These changes suggest that quantitatively successful angioplasty results in decreased collateral blood flow to the involved myocardium during pharmacologic stress. These improvements in coronary flow reserve cannot be predicted by visual analysis of angioplasty results. PMID- 8465778 TI - Angioplasty versus bypass surgery for multivessel coronary artery disease with left ventricular ejection fraction < or = 40%. AB - Patients with multivessel coronary artery disease and left ventricular dysfunction represent a high-risk subgroup in whom coronary artery bypass grafting has been shown to improve survival compared with that of medically treated patients. The comparative benefits and risks of coronary angioplasty and bypass surgery in this subgroup of patients are unclear. This study retrospectively analyzes 100 consecutive patients treated with bypass surgery compared with a matched, concurrent cohort of 100 treated with multivessel angioplasty. Early results favored angioplasty; a hospital stay of 12.8 days was noted in the bypass group compared with 4.3 days in the angioplasty group (p < 0.001). In-hospital mortality rates were similar in the bypass (5%) and angioplasty (3%) groups (p = NS). Stroke was observed significantly more often in the bypass group (7 vs 0%). However, late follow-up favored bypass patients; repeat revascularization procedures and late myocardial infarction occurred more frequently during follow-up in the angioplasty group. During 5-year follow-up, superior relief from disabling angina (99 vs 89%; p = 0.01) and a trend toward improved survival (76 vs 67%; p = 0.09) were observed in the bypass group as compared with the angioplasty group. Multivariate correlates of late mortality included age and incomplete revascularization, but not mode of revascularization. Thus, in patients with multivessel coronary artery disease and left ventricular dysfunction, early results favor angioplasty, whereas late follow-up favors bypass surgery. However, late survival was similar in both groups of patients who were completely revascularized. PMID- 8465779 TI - Diagnosis of right ventricular infarction by overlap images of simultaneous dual emission computed tomography using technetium-99m pyrophosphate and thallium-201. AB - The validity of dual energy single-photon emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m PPi) and thallium-201 for the diagnosis of right ventricular (RV) infarction, and the clinical features of RV infarction, were investigated in 190 patients with acute myocardial infarction. Diagnosis of RV infarction was performed by Tc-99m PPi accumulation in the RV myocardium on thallium-201 and Tc-99m PPi over-lay images at the dual SPECT with simultaneous imaging taken 2 to 9 days after the onset of myocardial infarction. Thirty RV infarctions were found among the 190 patients with left ventricular infarction (15.8%): 29 (97%) in association with the inferior and 1 (3%) with the lateral infarction. Tc-99m PPi accumulation was mostly observed in the posterior wall of the right ventricle. A total occlusion or a severe stenosis of the right coronary artery was demonstrated angiographically in 92% of the patients with RV infarction. The prevalence of RV infarctions was significantly lower in patients who achieved successful early reperfusion than in those who did not (26.7 vs 68.4%, respectively, p < 0.01). However, a successful early reperfusion therapy could not significantly decrease the rate of RV involvement in patients without significant collateral flow (p < 0.01). Thus, dual isotope SPECT with Tc-99m PPi and thallium-201 can be used as a reliable method for the diagnosis of RV infarction. PMID- 8465780 TI - Rationale and design of a secondary prevention trial of increasing serum high density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial). AB - Controlled clinical trials have demonstrated the efficacy of reducing the blood levels of low-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men. However, a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction. Therefore, the effect of administering 400 mg of bezafibrate retard daily versus placebo (double blind) to patients with myocardial infarction preceding randomization by 6 months to 5 years, or a clinically manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia, or both, is being investigated. Three thousand subjects (aged 45 to 74 years) are being enrolled from 19 cardiac departments in Israel, with total serum cholesterol between 180 and 250 mg/dl, high-density lipoprotein cholesterol < or = 45 mg/dl and triglycerides < or = 300 mg/dl. In addition, low-density lipoprotein cholesterol concentrations are required to be < or = 180 mg/dl (< or = 160 mg/dl for patients aged < 50 years). Patients needing lipid-modifying therapy, exhibiting > or = 1 prespecified exclusion criterion or not giving informed consent, or a combination, are not randomized. The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infarction, and sudden death. The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence of > or = 15% by 20 to 25% over an average follow-up period of 6.25 years, through early 1998, when the last patient recruited will have completed 5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465781 TI - Trans-fatty acid patterns in patients with angiographically documented coronary artery disease. AB - The plasma trans-fatty acids of 47 patients with angiographically documented coronary artery disease were compared with those of 56 reference subjects using high-resolution capillary column gas-liquid chromatography to test the hypothesis that trans-fatty acid intake is a risk factor for cardiovascular disease. Individual and total trans-fatty acids were higher in patients than in reference subjects (1.38 vs 1.11% for total trans-fatty acids, p < 0.003; 0.40 vs 0.31% for palmitoleic acid trans, p < 0.001; and 0.28 vs 0.22% for linoleic acid trans, p < 0.007). High-density lipoprotein (HDL) cholesterol and HDL cholesterol/total cholesterol were negatively correlated (r = -0.29, p < 0.004; and r = -0.35, p < 0.001, respectively), whereas triglycerides, total cholesterol and low-density lipoprotein cholesterol were positively correlated (r = 0.47, p < 0.001; r = 0.22, p < 0.03; r = 0.20, p < 0.05, respectively) with palmitoleic acid trans. The correlations were similar and significant for linoleic acid trans, but less strong for total trans-fatty acids (which is more difficult to measure and has greater variability). Saturated and trans-fatty acids and total cholesterol are positively associated, whereas HDL/total cholesterol and polyunsaturated fatty acids are negatively associated with coronary artery disease. These results are consistent with the hypothesis that dietary trans-fatty acids are a cardiovascular risk factor. PMID- 8465782 TI - Daily physical activity levels in congestive heart failure. AB - To determine the level of daily physical activity routinely performed by patients with congestive heart failure (CHF) and the ability of clinical and laboratory assessments of function to predict peak daily activity levels, 45 patients with CHF were evaluated in the laboratory and during 2 days of usual activity. Subjects performed symptom-limited treadmill exercise tests with respiratory gas analysis and wore a Vitalog activity monitor with continuous measurement of heart rate and body motion. Mean maximal oxygen uptake for this sample was 16.8 ml/kg/min. Peak daily physical activity involved walking on a flat surface (44%), or general activities (housework/yardwork, 42%). Most subjects were asymptomatic (49%) during daily physical activity, 22% noted dyspnea, 16% fatigue and 13% sore muscles/joints. Perceived intensity of peak daily physical activity (mean = 4.19, SD = 2.21) was similar to perceived exertion (mean = 3.73, SD = 1.37) reported at ventilatory threshold measured during treadmill exercise testing. Subjects may control their peak daily physical activity to minimize symptoms experienced. It was further observed that current methods of assessing functional capacity in these patients were inadequate for estimating the peak level of daily activity. In conclusion, daily physical activity levels are low in patients with congestive heart failure and a gap exists between exercise capacity and actual performance of daily physical activity. PMID- 8465783 TI - Adjustable tricuspid valve annuloplasty assisted by intraoperative transesophageal color Doppler echocardiography. AB - Intraoperative transesophageal echocardiography (TEE) can play a major role in active guidance of cardiac surgery. This study describes a new application of TEE for assisting tricuspid suture annuloplasty. Twenty-five patients (aged 52 +/- 11 years) who underwent mitral valve replacement and tricuspid valve annuloplasty were studied intraoperatively by TEE. After cardiopulmonary bypass, the suture annuloplasty was adjusted on the beating heart until palpable regurgitation was eliminated. Further adjustment of the suture was performed under echocardiographic guidance until color Doppler flow imaging showed the most adequate correction of tricuspid regurgitation (TR). A significant decrease in the semiquantitative grade of TR, of regurgitant jet area and of the ratio jet area/right atrial area was obtained when the suture was adjusted under echocardiographic guidance. The peak inflow velocity and the gradient across the tricuspid valve did not show significant changes throughout the procedures. The results showed that the tricuspid suture annuloplasty guided by TEE enables a substantial reduction in residual TR without creating valve stenosis. PMID- 8465784 TI - Left ventricular diastolic pressure-volume response immediately after successful percutaneous transvenous mitral commissurotomy. AB - The left ventricular (LV) diastolic pressure-volume response after percutaneous transvenous mitral commissurotomy (PTMC) was investigated to determine whether it was related to the baseline conditions of the left ventricle. Left ventriculography was performed, and the measurements of LV pressure were obtained in 32 patients before and after PTMC. Mitral valve area increased from 1.0 +/- 0.3 to 1.9 +/- 0.4 cm2 (p < 0.005) after PTMC, which caused a decrease in left atrial mean pressure (14.8 +/- 5.9 to 7.4 +/- 2.7 mm Hg; p < 0.005). LV end diastolic pressure increased in all patients 5 minutes after PTMC. However, patients could be divided into 2 groups according to the following changes in LV end-diastolic pressure 20 minutes after PTMC: In 22 patients, LV end-diastolic pressure returned to the near-baseline level 20 minutes after PTMC (before 5.0 +/ 2.2, 5 minutes after 8.6 +/- 3.1, and 20 minutes after 6.3 +/- 2.5 mm Hg) with a significant increase in LV end-diastolic volume index (64 +/- 12 to 74 +/- 14 ml/m2; p < 0.001) and augmentation of LV stroke volume index (39 +/- 9 to 47 +/- 11 ml/m2; p < 0.001). However, in the remaining 10 patients with a larger LV volume (> 80 ml/m2) and reduced ejection fraction (< 50%) at baseline, LV end diastolic pressure further increased 20 minutes after PTMC (before 5.5 +/- 2.8, 5 minutes after 7.8 +/- 2.7, and 20 minutes after 11.0 +/- 2.9 mm Hg) without significant changes in LV volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465785 TI - Immediate and one-year results of percutaneous mitral balloon valvuloplasty using Inoue and double-balloon techniques. AB - Many investigators have reported the results of percutaneous mitral valvuloplasty (PMV) using the Inoue or double-balloon technique, but to date, the immediate and long-term follow-up results of the 2 different procedures have not been compared in a prospective study. Therefore, a prospective, randomized trial was performed in 120 consecutive patients who underwent PMV using Inoue (n = 59; group I) or double (n = 61; group D) balloons. The success rate was 83% in group I, and 89% in group D. The magnitude of changes in mitral valve area and hemodynamic variables was the same in both groups. Immediately after dilation, the long diameter changes of the mitral orifice was greater in group D, and the increase in ejection fraction slope was significantly greater in group D. The duration of the total procedure, and the fluoroscopic time was significantly shorter in group I. The incidence of left-to-right shunt at the atrial level (Qp/Qs > 1.5) was 3.4% in group I and 4.9% in group D. Severe mitral regurgitation (grade > or = 3) occurred in 2 patients in each group. At follow-up, the mitral valve area had significantly decreased at 6 months, but no further changes occurred at 1-year follow-up in both groups. The long diameter of the mitral orifice was greater in group D until 6 months after PMV, but the difference was not apparent at 1-year follow-up. In conclusion, the Inoue and double-balloon techniques obtained equivalent results in the success rate and frequency of complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465786 TI - Rapid systolic intraventricular velocities after valve replacement for aortic stenosis. AB - To assess the frequency and severity of intraventricular gradients after valve replacement for severe valvular aortic stenosis 25 patients (valve area 0.59 +/- 0.19 cm2) were studied serially with Doppler echocardiography on postoperative days 1, 2, 3, 5 and 7. Pulsed Doppler was used to search for increased intraventricular velocities. Mid-to-late systolic intraventricular velocities > or = 2 m/s were defined as intraventricular gradients. In 13 patients (52%) intraventricular gradients were found at least once during days 1 to 7 (group A) and were most frequent at day 3 (44%). The typical location of these velocities was at the midventricular level close to the septum. In 4 patients intraventricular gradients > 64 mm Hg were found. Left ventricular end-diastolic and end-systolic diameters recorded preoperatively were significantly smaller in group A than in the rest (43.6 +/- 5.4 vs 50 +/- 5.8 mm and 24.6 +/- 5.6 vs 33.1 +/- 7.3 mm, both p < 0.05) and the fractional shortening was significantly higher (44 +/- 9 vs 34 +/- 9%, p < 0.05). It is concluded that intraventricular gradients are frequent during the first week after valve replacement for severe aortic stenosis. These gradients are mostly mild and transient in nature, but significant gradients associated with clinical deterioration may occur. The risk of developing intraventricular gradients postoperatively may be predicted at a preoperative echocardiographic examination, and patients with a small left ventricular cavity size and maintained contractility are at particular risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465787 TI - Comparison of mitral valve dimensions in adults with valvular aortic stenosis, pure aortic regurgitation and hypertrophic cardiomyopathy. AB - To assess the effect of left ventricular dilatation on mitral valve size, this study compared the dimensions of the mitral valve in patients with aortic valve disease and hypertrophic cardiomyopathy (HC). A total of 216 valves, removed at operation or necropsy, was analyzed by quantitative morphometric methods from: (1) 2 patient groups with dilated left ventricular cavities (i.e., 17 patients with dilated valvular aortic stenosis [AS] and 31 with pure aortic regurgitation), (2) 2 patient groups without dilated left ventricular cavities (i.e., 29 patients with nondilated AS and 94 with HC), and (3) 45 control subjects without heart disease. Mean mitral leaflet areas in patients with AS with dilated left ventricular cavities (13.1 +/- 3.0 cm2) and aortic regurgitation (12.0 +/- 3.6 cm2) were significantly greater than in control subjects (8.7 +/- 2.0 cm2; p < 0.001). Mean mitral leaflet areas in patients with AS without dilated left ventricular cavities (9.8 +/- 2.0 cm2) were similar to those of normal valves (p = NS). However, mean mitral leaflet area in patients with HC, in whom left ventricular cavities were also nondilated, was significantly greater (12.8 +/- 3.7 cm2) than in those with nondilated AS and in normal subjects (p < 0.001). Therefore, increased mitral leaflet area: (1) is often present in patients with aortic valve disease with dilated left ventricles in whom it appears to be secondary to left ventricular chamber dilatation; and (2) cannot be attributed to left ventricular cavity dilatation in patients with HC, since their cavities were of normal or small size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465788 TI - Prevalence and incidence of left ventricular dysfunction in patients with human immunodeficiency virus infection. AB - The prevalence and incidence of left ventricular (LV) dysfunction was examined in patients infected with the human immunodeficiency virus (HIV). Sixty-nine randomly selected patients diagnosed with HIV infection who were followed in HIV clinics were prospectively evaluated by 2-dimensional echocardiography. Mean follow-up duration was 11 months. Additionally, 39 consecutive HIV-infected patients referred to the Cardiomyopathy Service and found to have LV dysfunction by 2-dimensional echocardiography were also studied. Of the 39 referred patients, 34 (87%) were referred for recent onset, unexplained, congestive heart failure. During this time, the HIV clinic population comprised 1,819 alive and actively followed patients; the 39 cardiomyopathy referrals therefore constituted a crude rate of 2.1% for this population. Of the 69 prospectively studied patients without clinical heart disease, a 14.5% prevalence of global LV hypokinesia and an incidence of 18%/patient-year were found. During a maximal 18-month follow-up period, 4 prospective patients (5.8%) developed symptoms of congestive heart failure. A greater proportion of prospective and referred patients with LV dysfunction had CD4 counts < 100/mm3 (62 and 79%, respectively) than did that of those without LV dysfunction (35%). In conclusion, the high rate of unexpected LV dysfunction in this HIV-infected population suggests that early cardiac contractile abnormalities may involve a significant number of patients, most of whom have low CD4 counts. A subgroup of these patients appears to progress to symptomatic congestive heart failure. PMID- 8465789 TI - Usefulness of the bidirectional Glenn procedure as staged reconstruction for the functional single ventricle. AB - The bidirectional Glenn operation may be particularly useful as an intermediate procedure before Fontan correction in high-risk patients. From October 1989 through February 1992, 50 patients 1 to 60 months old (median 12) have undergone a bidirectional Glenn operation. Diagnoses included hypoplastic left heart syndrome in 21 patients, pulmonary atresia with intact ventricular septum in 10, tricuspid valve atresia in 9, other complex univentricular heart defects in 9, and Ebstein's anomaly in 1. Mean pulmonary vascular resistance was 2.2 +/- 0.2 Wood U (range 0.5 to 7.3) and mean pulmonary artery area Nakata index was 318 +/- mm2/m2 (range 80 to 821). Additional procedures were performed in 17 patients, including pulmonary artery reconstruction in 15 (29%) and bilateral caval anastomoses in 5 (10%). There were 4 hospital deaths (8%). Two deaths resulted from myocardial infarction in patients with pulmonary atresia with intact ventricular septum and sinusoids and 1 from severe pulmonary vascular disease in a patient with hypoplastic left heart syndrome. There was 1 late death from pneumonia. Actuarial survival is 92 +/- 4% at 1 month and beyond, with a mean follow-up of 13.4 +/- 1 months. Risk factor analysis showed that pulmonary vascular resistance > 3 Wood U and pulmonary artery distortion were associated with increased mortality. Twelve patients have undergone a Fontan procedure at a mean duration after bidirectional Glenn of 18 months with 1 death (8%). The bidirectional Glenn procedure provides excellent palliation in high-risk patients and appears useful as a staging procedure before Fontan correction. PMID- 8465790 TI - Aortic "recoarctation" at rest versus at exercise in children as evaluated by stress Doppler echocardiography after a "good" operative result. AB - The mechanism for exercise systolic hypertension after a "good" operative repair of coarctation of the aorta remains speculative. Twenty-four children (mean age +/- SD 10.3 +/- 3.8 years) were studied with continuous-wave Doppler echocardiography while they performed continuous, graded, maximal treadmill exercise. Patients were free of "recoarctation" based on conventional resting echocardiography. Measurements of ascending and descending aortic peak instantaneous systolic velocity were obtained at rest, throughout exercise and during recovery. Results were compared with 24 age- and gender-matched control subjects. Fifteen patients were normotensive (group 1) (peak systolic blood pressure, 147 +/- 21 mm Hg) and 9 developed systolic hypertension during exercise (group 2) (196 +/- 32 mm Hg) (p < 0.05) (control subjects, 143 +/- 21 mm Hg). Descending aortic peak systolic velocity at rest ranged from 1.50 +/- 0.27 m/s in the control group to 2.57 +/- 0.57 m/s (group 1) and 2.93 +/- 0.43 m/s (group 2) (p < 0.05, group 2 vs control). Differences were amplified at peak exercise with systolic velocity increasing to 4.26 +/- 0.61 m/s in group 2 but only to 3.61 +/- 0.70 m/s in group 1 and 2.26 +/- 0.38 m/s in control subjects (p < 0.05, group 2 vs group 1 and control). Seven patients developed a descending aortic diastolic velocity during exercise. Stepwise linear regression analysis identified 2 variables to be significant determinants of peak exercise systolic blood pressure in the "total" patient group: (1) age at exercise testing, and (2) descending aortic peak systolic velocity at peak exercise (r2 = 0.88, p < 0.001) (group 2, alone - r2 = 0.98, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465791 TI - Early results after pediatric cardiac transplantation with triple immunosuppression therapy. AB - Pediatric heart transplant recipients were previously reported to have higher early mortality and morbidity than do adult patients treated with triple immunosuppression therapy (steroids, azathioprine and cyclosporine). Nineteen patients (11 infants and 8 older children) underwent orthotopic transplantation using triple immunosuppression therapy. Surveillance for cellular rejection and coronary arteriopathy was performed with endomyocardial biopsy and selective coronary angiography in all patients, with continuous monitoring for hypertension and serious infection. Seventeen of 19 patients (89%; 10 infants and 7 older children) are current survivors, with a median follow-up of 29 months (range 17 to 94). There were 5 and 7 episodes of rejection in the first 12 months after transplantation in the infant and older groups, respectively, for actuarial freedom-from-rejection rates of 65% at 3 months and 54% at 12 months. Severe coronary arteriopathy was detected in 1 infant 11 months after transplantation. In the first 12 months after transplantation, there were 3 hospitalizations for infection, and 2 patients needed treatment for hypertension in the infant group, compared with 1 hospitalization for infection, and 4 patients on antihypertensives in the older group. An increased prevalence of noninfectious complications in the infant group led to significantly longer postoperative stays than in the older group (mean 27.3 vs 19.4 days; p < 0.05). The results indicate that cardiac transplantation using triple immunosuppression therapy in infants, children and adolescents is associated with a high survival rate, and low rates of rejection and serious infection. PMID- 8465792 TI - Left atrial appendage blood flow determined by transesophageal echocardiography in healthy subjects. AB - Transesophageal echocardiography was performed in 46 healthy subjects to define characteristics of normal left atrial appendage blood flow. Three different flow wave patterns were observed that were heart rate dependent (p < 0.01). A quadriphasic pattern, consisting of 2 diastolic forward (emptying) flow waves each followed by a backward (filling) flow wave, was present in 36 subjects (78%). Triphasic appendage flow was observed in 6 subjects (13%) and biphasic flow in 4 (9%). Mean heart rates among subjects with quadri-, tri- and biphasic flows were 75 +/- 11, 95 +/- 6 and 112 +/- 7 beats/min, respectively. Analysis of pulsed Doppler recordings of subjects with quadriphasic or triphasic appendage flow patterns showed that the onset of transmitral early diastolic peak flow wave was followed at 17 +/- 15 ms by the onset of pulmonary venous diastolic flow and at 43 +/- 17 ms by the onset of the first diastolic forward flow in the appendage. This sequence was constant and independent of heart rate (p < 0.01), suggesting a causal relation between left ventricular relaxation and the first diastolic forward flow wave in the appendage. The second diastolic forward flow followed the P wave on the electrocardiogram at 79 +/- 23 ms. Thus, left atrial appendage blood flow pattern in normal subjects is heart rate dependent, and ventricular relaxation appears to initiate early diastolic emptying of the appendage. PMID- 8465793 TI - Demographic features and prevalence of idiopathic myocarditis in patients undergoing endomyocardial biopsy. AB - From January 1985 through December 1990, 534 patients underwent endomyocardial biopsy at Johns Hopkins Hospital for suspected myocarditis. One hundred thirty eight (26%) biopsy specimens were diagnosed histologically by 2 cardiac pathologists as either active (n = 85, 16%) or borderline (n = 53, 10%) myocarditis. Of the 138 patients, 60 were excluded based on either specific concurrent clinical conditions or noncongestive heart failure presentations. Immunohistochemical staining for common leukocyte antigen infiltrating cells performed on the remaining 78 specimens confirmed the presence of focal or multifocal inflammatory infiltrates in 58, of which 49 had histologic evidence of active myocarditis. All 49 patients presented with congestive heart failure and left ventricular ejection fractions of < 40%. Compared with patients with either idiopathic dilated cardiomyopathy (n = 207) or ischemic cardiomyopathy (n = 44), these patients with myocarditis had a less striking male predominance (58 vs 69 and 83%, respectively) (p = 0.02) and were younger (43 +/- 16 vs 50 +/- 17 and 55 +/- 13 years, respectively, p = 0.005). Racial distributions were similar. A recent history of a discrete flu-like illness was obtained in 52%, two-thirds of which were clustered between the months of December and March. Onset of heart failure peaked between December and April (63% and was low between May through September (22%). A peak in the proportion of patients found to have active myocarditis on biopsy occurred in 1986 (17 vs 7 to 10% in other years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465794 TI - Left ventricular myocardial function in myotonic dystrophy. AB - Myotonic dystrophy is an autosomal dominant disease affecting many organ systems, including the heart. Abnormalities of the cardiac conduction system are a frequent and well-documented finding in this neuromuscular disease, whereas overt signs of heart failure are rarely reported. However, controversy exists about the prevalence of preclinical left ventricular (LV) dysfunction in patients with myotonic dystrophy who have no symptoms of heart failure. To address this issue, load-independent LV function indexes were compared in patients with myotonic dystrophy and in normal subjects. LV measurements were obtained with M-mode echocardiography in 43 consecutive patients with myotonic dystrophy (mean age 35 +/- 14 years) who had no clinical evidence of heart failure, and in 35 sex- and age-matched controls. A cuff sphygmomanometer was used to determine blood pressure. No difference was found between patients and control subjects in the percentage of LV ejection fraction predicted for end-systolic stress (103 +/- 7 vs 103 +/- 7%; p = 0.97) or in the end-systolic stress/volume index ratio (2.9 +/ 0.5 vs 2.7 +/- 0.4 dyne7/cm3; p = 0.09). Similarly, no significant difference in LV myocardial function was detected between the 19 patients with a mild degree of the neuromuscular disease and in the 24 with a moderate or severe degree of the disease. Finally, LV myocardial function was compared between patients with myotonic dystrophy and atrioventricular or intraventricular conduction disturbances (n = 8) and those without these disturbances (n = 35), but no significant difference in the percentage of LV ejection fraction predicted for end-systolic stress or in the end-systolic stress/volume index ratio could be detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465795 TI - Effects of ibopamine on the increase in plasma norepinephrine levels during exercise in congestive heart failure. PMID- 8465796 TI - Effect of balloon valvuloplasty for mitral stenosis on right ventricular function. PMID- 8465797 TI - Regulation of QT interval during postural transitory changes in heart rate in normal subjects. PMID- 8465798 TI - Prevalence of atherothrombotic brain infarction and extracranial carotid arterial disease, and their association in elderly blacks, Hispanics and whites. PMID- 8465799 TI - How should physicians view heart failure? The philosophical and physiological evolution of three conceptual models of the disease. AB - During the last 50 years, physicians have developed three distinct conceptual models of heart failure that have provided a rational basis for the treatment of the disease. In the 1940s through the 1960s, physicians regarded heart failure principally as an edematous disorder and formulated a cardiorenal model of the disease in an attempt to explain the sodium retention of these patients. This model led to the widespread use of digitalis and diuretics. In the 1970s and 1980s, physicians viewed heart failure principally as a hemodynamic disorder and formulated a cardiocirculatory model of the disease in an attempt to explain patients' symptoms and disability. This model led to the widespread use of peripheral vasodilators and the development of novel positive inotropic agents. Now, in the 1990s, physicians are beginning to think about heart failure as a neurohormonal disorder in an attempt to explain the progression of the disease and its poor long-term survival. This new conceptual framework has led to the widespread use of converting-enzyme inhibitors and the development of beta blockers for the treatment of heart failure. Which conceptual model most accurately describes the syndrome of heart failure and leads physicians to utilize the most effective treatment? This paper critically reviews the available evidence supporting and refuting the validity of all three models of heart failure. We conclude that, to varying degrees, all three approaches provide useful, but incomplete, insights into this physiologically complex and therapeutically challenging disease. PMID- 8465800 TI - The xamoterol experience in the treatment of heart failure. AB - Beta blockers may benefit patients with dilated cardiomyopathy but low output failure can be a problem. Thus a beta 1-selective beta blocker with about 45% intrinsic sympathomimetic activity (ISA), such as xamoterol, was thought to have a desirable pharmacologic profile. Long-term studies of xamoterol in patients with idiopathic dilated cardiomyopathy have shown improved cardiac performance and exercise tolerance, while exercise heart rate, left ventricular ejection fraction, and pulmonary artery wedge pressure were decreased. This improvement in exercise capacity and overall quality of life in patients treated with xamoterol has been confirmed in further controlled trials of patients with mild-to-moderate heart failure (NYHA class I and II). However, in patients with moderate-to-severe heart failure (NYHA class III and IV), mortality was unfavorably influenced by xamoterol. The therapeutic role of xamoterol in patients with heart disease needs further refinement. PMID- 8465801 TI - p values, hypothesis tests, and likelihood: implications for epidemiology of a neglected historical debate. AB - It is not generally appreciated that the p value, as conceived by R. A. Fisher, is not compatible with the Neyman-Pearson hypothesis test in which it has become embedded. The p value was meant to be a flexible inferential measure, whereas the hypothesis test was a rule for behavior, not inference. The combination of the two methods has led to a reinterpretation of the p value simultaneously as an "observed error rate" and as a measure of evidence. Both of these interpretations are problematic, and their combination has obscured the important differences between Neyman and Fisher on the nature of the scientific method and inhibited our understanding of the philosophic implications of the basic methods in use today. An analysis using another method promoted by Fisher, mathematical likelihood, shows that the p value substantially overstates the evidence against the null hypothesis. Likelihood makes clearer the distinction between error rates and inferential evidence and is a quantitative tool for expressing evidential strength that is more appropriate for the purposes of epidemiology than the p value. PMID- 8465802 TI - A comparison of prospective and retrospective assessments of diet in the study of breast cancer. AB - Fat intake was examined in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer. Among the Nurses' Health Study cohort members who completed a food frequency questionnaire and were free of cancer in 1986, 398 were diagnosed with breast cancer during 2 years of follow-up. These cases and 798 age-matched controls (cohort members who also completed a dietary questionnaire in 1986 but did not develop breast cancer) were sent another food frequency questionnaire in 1989 inquiring about their diet in 1985. Three hundred cases and 602 controls responded to the second questionnaire. The age-adjusted analysis using the prospective (1986) questionnaire demonstrated no appreciable associations between breast cancer incidence and intakes of total fat (odds ratio (OR) between highest and lowest quintiles = 0.87; 95% confidence interval (CI) 0.54-1.40) and saturated fat (OR = 0.97; CI 0.64-1.46). The age-adjusted analysis using the retrospective (1989) questionnaire suggested positive associations between breast cancer incidence and intakes of total fat (OR = 1.43; 95% CI 0.90-2.27) and saturated fat (OR = 1.38; 95% CI 0.89-2.13). When nutrients were adjusted for total energy intake, the direction and magnitude of the differences between the prospective and retrospective analyses were similar to the analyses unadjusted for energy intake. These results suggest that case-control studies of diet and breast cancer may yield biased associations between fat intake and the risk of breast cancer. PMID- 8465803 TI - A cohort study of alcohol consumption and risk of breast cancer. AB - The association between alcohol consumption and breast cancer risk was examined in 519 newly incident, histologically confirmed cases of breast cancer diagnosed between 1982 and 1987 within a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a self-administered food frequency questionnaire including alcohol consumption at enrollment into the study prior to their breast cancer diagnosis. For the total cohort, only a weak association between total alcohol consumption and breast cancer risk is observed, the adjusted relative risk for those drinking 30 or more g/day being 1.22 (95% confidence interval (CI) 0.78-1.90) compared with nondrinkers. There is some evidence for a positive association in women who were premenopausal at the time of enrollment for whom there was a monotonic increase in risk with increasing alcohol intake. Compared with nondrinkers, the adjusted relative risk for alcohol consumption of between 0 and < 10 g of alcohol daily was 1.11 (95% CI 0.71-1.71), between 10 and < 20 g was 1.37 (95% CI 0.79-2.36), between 20 and < 30 g was 1.51 (95% CI 0.80-2.86), and > or = 30 g was 1.86 (95% CI 0.96-3.66; p (trend) = 0.07). These findings contrasted with the results for postmenopausal women where there appeared to be no evidence of any relation. The association in premenopausal women is generally reasonably consistent with that of other studies that have found positive associations with alcohol intake. PMID- 8465804 TI - Association of alcohol intake, cigarette smoking, and occupational status with the risk of idiopathic osteonecrosis of the femoral head. AB - To investigate the association of alcohol intake, cigarette smoking, occupation, and other factors with the development of idiopathic osteonecrosis of the femoral head, a nationwide multicenter case-control study was conducted in Japan during 1988-1990, comparing 118 cases with no history of systemic corticosteroid use with 236 controls matched for sex, age, ethnicity, clinic, and date of initial examination. The risks of developing femoral head necrosis associated with potential risk factors were estimated by adjusted relative odds obtained by a conditional logistic regression model. The elevated relative odds were observed for occasional drinkers (relative odds = 3.2, 95% confidence interval 1.1-9.2) and regular drinkers (relative odds = 13.1, 95% confidence interval 4.1-42.5) with a significant dose-response relation (p < 0.001). For current drinkers, the relative odds were 2.8, 9.4, and 14.8 for < 320, 320-799, and > or = 800 g/week of ethanol intake, respectively. An increased risk was found for current smokers (relative odds = 4.7, 95% confidence interval 1.5-14.5), but a linear increasing trend in the cumulative effect of smoking was not evident at 20 pack-years or over. A weak but significant dose-response relation was observed for daily occupational energy consumption (p < 0.05). The present study confirmed the strong association of alcohol intake and positive association of cigarette smoking and suggested the role of heavy physical work. PMID- 8465805 TI - Work activities and the onset of first-time low back pain among New York City fire fighters. AB - In a prospective study of first-time low back pain among New York City fire fighters, a total of 115 cases and 109 randomly selected controls were interviewed by telephone between December 1988 and July 1989 to examine the role of recent work activities in the onset of first-time low back pain. After adjusting for known risk factors and off-duty activities, statistically significant high-risk work activities included operating a charged hose inside a building (odds ratio (OR) = 3.26), climbing ladders (OR = 3.18), breaking windows (OR = 4.45), cutting structures (OR = 6.47), looking for hidden fires (OR = 4.32), and lifting objects > or = 18 kg (OR = 3.07). Low-risk activities included connecting hydrants to pumpers (OR = 0.36), pulling booster hose (OR = 0.19), and participating in drills (OR = 0.09) or physical training (OR = 0.16). When further adjusted for exposure to smoke (OR = 13.59), a surrogate for severity of alarms, the ORs associated with high-risk activities were no longer significant. This, however, does not diminish the role of activities in the onset of low back pain. Instead, it suggests an inseparable role for activities and environmental hazards. To examine this, the risk of low back pain was measured within five work zones sequential in time relative to location and distance from a structural fire. The risk gradually increased as the fire fighter moved away from the firehouse (OR = 0.10) and closer to the site of fire (OR = 3.91). PMID- 8465807 TI - Prevalence and correlates of lower extremity arterial disease in elderly women. AB - Although lower extremity arterial disease occurs in 15-20% of the population over the age of 75 years, little is known about the etiology of the disease in women. In this cross-sectional study involving 1,601 healthy elderly women (mean age, 71 years; range, 65-93 years), the occurrence of lower extremity arterial disease was assessed noninvasively by measuring brachial and ankle pressures bilaterally. Disease prevalence ranged from 2.9% in those aged 65-69 years to 15.5% in those aged 80 years or older. Approximately 20% of those with disease had symptoms of claudication. Age, systolic blood pressure, and current smoking status were strong independent risk factors for arterial disease; a history of arthritis, use of nonthiazide diuretics, current coffee drinking, and upper body obesity were also independent correlates. The number of pack-years in current and former smokers and the number of cigarettes per day used by current smokers showed a dose-response relation with disease. The population attributable risk for current smoking was 26%. The major correlates for symptomatic arterial disease were current smoking and systolic blood pressure. It is concluded that the major risk factors for lower extremity arterial disease in elderly women are similar to those in men. Preventive efforts should focus on smoking cessation and management of hypertension. PMID- 8465806 TI - Divergent age-associated patterns of high density lipoprotein cholesterol and its percentage in Jewish and Moslem Arab Israeli children and adolescents: the Petach Tikva Project. AB - We studied three groups of Israeli Jewish schoolchildren in and surrounding Petach Tikva, Israel, cross-sectionally, at ages 9-10, 13-14, and 16-18 years, and compared lipid and lipoprotein levels and age-associated lipoprotein patterns in the same age groups of boys and girls in neighboring Israeli Moslem Arab schools during 1986-1987. Moslem children displayed striking differences in the levels of lipids and age-associated patterns of lipoproteins compared with Jewish schoolchildren. The mean total cholesterol levels were lower in the Moslem children, in both sexes, in every age grouping. High density lipoprotein cholesterol (HDL-C) levels were significantly higher at age 16-18 in the Moslem boys than in the Jewish boys. While the Jewish boys displayed a previously reported "typical" pattern of lower HDL-C levels postpuberty compared with prepuberty, the Moslem boys had markedly higher mean HDL-C levels at age 16-18 compared with those at age 9-10. The Moslem girls also had higher HDL-C levels at age 16-18 than those observed in the age 9-10 group. Concomitantly higher HDL-C levels (HDL-C/total cholesterol (%)) were seen in the Moslem boys and girls, at age 16-18 compared with age 9-10, but were not observed in the Jewish children. The identification of an ethnic group in whom HDL-C appears to increase at or near puberty could provide opportunities to elucidate factors that may increase HDL-C in individuals or in populations. PMID- 8465808 TI - Prevalence of bulimic behaviors and bulimia among a sample of the general population. AB - Data are presented on the prevalence of bulimic symptoms and bulimia among a sample of adults residing in north-central Florida (n = 2,075). The data were gathered between 1984 and 1986. The sample included 1,736 whites and 339 blacks, of whom 1,040 were females and 1,035 were males. A current diagnosis of bulimia was made using the criteria of the Diagnostic and Statistical Manual, Third Edition (DSM-III), of the American Psychiatric Association. Females had significantly higher rates than did males on nine of the 10 bulimic symptoms. Blacks had symptom rates equal to or greater than whites on eight of the 10 items, and those in the lowest socioeconomic groups (SES) had rates greater than those in the highest SES group on nine of the 10 symptoms. Eight persons, 0.4% of the total sample, met the DSM-III criteria for a diagnosis of bulimia. These included six white females and two black males. Five of the females were aged 18 29 years; one was over 45. Five of the females were in the lower middle SES group; one was in the upper middle SES group. Both of the black males were aged 30-44, and both were in the lowest SES group. The data emphasize the need to distinguish between bulimic type symptoms and bulimia when estimating the prevalence of eating-related problems in the general population. PMID- 8465809 TI - Relation of tubal infertility to history of sexually transmitted diseases. AB - We studied the history of sexually transmitted diseases in 283 nulliparous women diagnosed with infertility due to tubal adhesions or occlusion and 3,833 women admitted for delivery at seven collaborating hospitals. The adjusted risks of tubal infertility associated with the history of each sexually transmitted disease were estimated by the odds ratios obtained by multiple logistic regression. Women who reported prior infection with gonorrhea were at a significantly increased risk of tubal infertility (relative odds = 2.4, 95% confidence interval 1.3-4.4). In addition, the risk of tubal infertility was almost twice as high in women who recalled previous trichomoniasis compared with women with no such infection (relative odds = 1.9, 95% confidence interval 1.3 2.8). Furthermore, there was a trend of increasing risk with an increasing number of episodes of gonorrhea or trichomoniasis. PMID- 8465811 TI - Re: "Race/ethnicity and other risk factors for gestational diabetes". PMID- 8465810 TI - Re: "Congenital defects and electric bed heating in New York State: a register based case-control study". PMID- 8465812 TI - Mechanisms of proteinuria in noninflammatory glomerular diseases. AB - Neither the initiating factors nor the proximate causes of injury that produce proteinuria in nephrotic syndrome have been clearly defined. Immune mechanisms have been postulated in minimal-change nephrotic syndrome (MCNS), focal segmental glomerular sclerosis (FSGS), and glomerular sclerosis associated with human immunodeficiency virus (HIV) infection. Circulating factors have been proposed in MCNS and FSGS, although no specific mediator has been identified. Prompt remission of proteinuria following steroid treatment and the presence of altered immune responsiveness in patients with MCNS have been used to support the participation of an immune mechanism in the pathogenesis of MCNS. Both FSGS and HIV-related nephropathy are usually steroid-resistant. Immune mechanisms are postulated in FSGS because of early recurrence after transplantation, and in HIV related nephropathy because of the numerous associated immune abnormalities. Experimental models of nephrotic syndrome based on neutralization of glomerular charge, toxic injury to podocytes, injection of antibodies to glomerular components, or abnormalities in transgenic mice have been used to define mechanisms of glomerular injury. This review summarizes physiologic and immunologic abnormalities in MCNS, FSGS, and HIV-associated nephropathy and in several experimental models of nephrotic syndrome, and outlines the immunologic mechanisms and cellular reactions that may be responsible for glomerular dysfunction in these entities. PMID- 8465813 TI - Effect of dietary protein on glomerular renin secretion. AB - Previous studies from our and other laboratories demonstrated that dietary protein restriction lowers plasma renin activity by impairing renin release. The effect of protein intake on glomerular renin secretion has not been investigated. Accordingly, we studied male Sprague-Dawley rats weighing 180 to 200 g for 3 weeks that were receiving isocaloric diets that provided either standard 20% protein (SP) or low 6% protein (LP). Renin secretion was measured in the glomeruli isolated from these rats, at baseline and following stimulation with arachidonic acid and isoproterenol. The activity of plasma renin (3.0 +/- 0.5 ng/mL/min on SP v 1.1 +/- 0.1 ng/mL/min on LP) was significantly (P < 0.02) lower on LP intake. In contrast, glomerular renin content (22.9 +/- 0.7 ng/micrograms protein on SP v 32.3 +/- 1.4 ng/micrograms protein on LP) was significantly (P < 0.01) higher on the LP diet. Furthermore, renin secretion (ng/mL/h) from the isolated glomeruli at baseline (3.9 +/- 1.0 on SP v 12.5 +/- 3.0 on LP, P < 0.02), and following incubation with arachidonic acid 10(-5) mol/L (5.9 +/- 1.7 on SP v 19.6 +/- 3.1 on LP, P < 0.005), and isoproterenol 10(-3) mol/L (6.0 +/- 0.5 on SP v 17.3 +/- 3.3 on LP, P < 0.01) was significantly higher on the LP diet. These studies suggest that dietary protein restriction impairs in vivo renin release. In contrast, in vitro glomerular renin release is augmented by protein restriction. The factors modulating in vivo renin release require further characterization. PMID- 8465815 TI - Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group. AB - Histological indices of renal pathology in lupus nephritis have been proposed as prognostic signs and as a method to quantitate therapeutic response. We tested the reproducibility of the activity (AI) and chronicity indices (CI) in the renal biopsies from 83 patients with lupus nephritis, enrolled in a controlled therapeutic trial. The AI/CI were calculated separately by four renal pathologists using published criteria. Pair-wise Spearman's rank correlation coefficient was used to examine the relationship among the scores of the four raters, and their degree of reproducibility was evaluated using the coefficient of reliability. The mean CI scores ranged from 2.84 to 4.61, and the mean AI ranged from 9.64 to 12.89. The correlation among the different pathologist's scores ranged from 0.44 to 0.63 for the AI and 0.60 to 0.76 for the CI. One pathologist (M.M.S.) rated the biopsies twice, and the correlation between the two ratings was 0.58 for the AI and 0.74 for the CI. Thus, the AI and CI calculated by different pathologists and the temporally separate observations of a single observer were only moderately correlated. The reproducibility of a single rating was low, showing a reliability coefficient of 0.48 for the AI and 0.57 for the CI. The low reliability coefficient suggests that the variability among pathologists was the result of interpretative differences. We conclude that the AI/CI are too subjective to be used as therapeutic guides or as prognosticators. PMID- 8465814 TI - Neutrophil alloantibodies react with cytoplasmic antigens: a possible cause of false-positive indirect immunofluorescence assays for antibodies to neutrophil cytoplasmic antigens. AB - Antibodies to neutrophil cytoplasmic antigens (ANCA) can be detected in patients with Wegener's granulomatosis and systemic vasculitis. During pregnancy or following transfusion, subjects sometimes produce alloantibodies to neutrophil antigens. If patient sera being tested for ANCA contain alloantibodies directed at neutrophil antigens that residue in the cytoplasm, the results may be difficult to interpret. At least one neutrophil antigen, NB1, is expressed on both neutrophil plasma membranes and secondary granules. We tested alloantibodies specific for neutrophil antigens NA1, NA2, NB1, NB2, 5b, 9a, and Mart in an ANCA indirect immunofluorescence (ANCA-IF) assay to determine if these alloantibodies reacted with neutrophil cytoplasmic or granule antigens. Alloantibodies specific for neutrophil antigens NA1, NA2, NB2, 5b, and 9a did not react with neutrophil cytoplasmic components. However, all three NB1 alloantibodies studied demonstrated a cytoplasmic pattern of immunofluorescence (C-ANCA) when NB1 positive neutrophils were tested. While control ANCA resulted in cytoplasmic immunofluorescence of all neutrophils from each donor tested, NB1 antibodies reacted with a subpopulation of neutrophils from some donors. Cytoplasmic immunofluorescence was also observed with an antibody directed against the Mart neutrophil antigen. The Mart antigen is located on integrin CR3 (CD11b/CD18). To confirm that these reactions were due to anti-Mart, monoclonal antibodies to CD11b and CD18 were also tested and found to cause cytoplasmic immunofluorescence. When the ANCA-IF assay was performed using neutrophils that did not express Mart or NB1 antigen, cytoplasmic immunofluorescence was seen with the ANCA control antisera, but not with the NB1 or Mart alloantibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465816 TI - A race-controlled human leukocyte antigen frequency analysis in lupus nephritis. The South-Eastern Organ Procurement Foundation. AB - Systemic lupus erythematosus (SLE) has higher incidence and mortality rates in addition to a greater risk for nephropathy in African Americans (blacks), compared with whites. We analyzed the South-Eastern Organ Procurement Foundation (SEOPF) database from 1982 through 1986 to determine if variation in human leukocyte antigen (HLA) frequencies, beyond those normally present between the races, were associated with lupus nephritis (LN). HLA antigen frequencies in 271 black and 230 white renal transplant recipients with LN as the cause of end-stage renal disease (ESRD) were compared with 4,506 race-matched cadaveric kidney donor controls. Odds ratios (ORs) and chi-square values were computed to assess the prevalence of each HLA phenotype among the cases versus the controls separately for blacks and whites. HLA-B8 and -DR2 frequencies were increased, and HLA-DR4 frequency was decreased in cases of both races compared with race-matched controls (race-combined ORs, 1.68, 1.46, and 0.49, respectively; all P < 0.01). Race-specific analyses showed that HLA-DR6 was decreased in black cases versus black controls (OR, 0.48; P < 0.001) and HLA-DR3 was increased in white cases versus white controls (OR, 1.88; P < 0.001). HLA-B8 and DR2 are positively associated and HLA-DR4 is negatively associated with LN in patients of both races. HLA-DR3 and -DR6 demonstrate race-specificity in LN and place whites at a disadvantage relative to blacks. It is likely that non-HLA-mediated genetic factors and/or environmental factors contribute to the increased risk of nephritis observed in black patients with SLE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465817 TI - The effect of racial misclassification on estimates of end-stage renal disease among American Indians and Alaska Natives in the Pacific Northwest, 1988 through 1990. AB - Although several recent studies have documented a high incidence of end-stage renal disease (ESRD) among American Indians (AI) and Alaska Natives (AN), racial misclassification of AI/AN as members of other races on disease registries has not been accounted for. We conducted a study to link the Northwest Renal Network (NRN) ESRD database, which includes persons known to have begun dialysis in Idaho, Oregon, and Washington, and the Indian Health Service (IHS) patient registration file, which includes AI/AN enrolled for health care provided or paid for by IHS in the same states, for the period January 1, 1988 to December 31, 1990. Among the 3,356 persons included on the NRN ESRD database, 68 (2.0%) were coded as AI/AN. Of the 68 listed as AI/AN, 54 (79.4%) were identified on the IHS patient registration file. In addition to the 68 cases coded on the NRN as AI/AN, we identified 12 cases that were definitively matched to the IHS patient registration file but not coded AI/AN on the NRN. The age-adjusted annual incidence of ESRD treatment initiation among AI/AN in Idaho, Oregon, and Washington was 267.5 per million according to original racial coding on the NRN, but it increased to 311.6 per million after correction for racial misclassification. Among IHS-registered AI/AN, the annual incidence increased from 394.1 per million to 474.3 per million. Racial misclassification of AI/AN in ESRD registries may result in underestimates of AI/AN ESRD incidence for the United States. PMID- 8465818 TI - The familial risk of end-stage renal disease in African Americans. AB - African Americans have higher overall incidence rates of end-stage renal disease (ESRD) compared with American whites. Hypertensive nephrosclerosis (HN), nephropathy secondary to diabetes mellitus types I and II, and chronic glomerulonephritis (CGN) all occur more frequently in African Americans. To explore the possibility that hereditary factors may play a role in the increased risk of ESRD in African Americans, the family history of 131 African American hemodialysis patients (cases) was compared with 115 age-, sex-, and race-matched non-ESRD controls. Odds ratios (ORs) were calculated to define the prevalence of a relative with ESRD among cases versus controls. Chi-square values were estimated from a log-linear model, while controlling for gender, to test for significance of ORs. Forty percent (12/30) of HN cases, 35% (18/51) of type II diabetes mellitus-induced renal failure cases, and 13% (5/38) of CGN cases had a first-, second-, or third-degree relative with ESRD. The presence of a first degree relative with ESRD increased an African American's risk for developing ESRD ninefold (OR, 9.13; 95% confidence interval [CI], 2.6 to 31.8; P < 0.001). The presence of a first- or second-degree relative increased the risk fivefold (OR, 5.23; 95% CI, 2.2 to 12.3; P < 0.0002). First-, second-, or third-degree relatives with ESRD were more prevalent among cases with ESRD due to hypertension and type II diabetes mellitus compared with CGN (P < or = 0.05). Gender differences among the ORs were nonsignificant (P > 0.2) and socioeconomic class (level of education and income) did not differ markedly between cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465819 TI - Stimulation of mononuclear cells by contact with cuprophan membranes: further increase of beta 2-microglobulin synthesis by activated late complement components. AB - Contact of mononuclear cells (MNC) with cuprophan membranes in vitro causes an increase in beta 2-microglobulin (beta 2m) synthesis. Since in vivo the dialyzer membrane is rapidly coated with plasma proteins, contact activation of MNC was tested in the presence of normal human serum (NHS). After contact with cuprophan, deposition of C5b-9 on the cells was seen, followed by an increase in beta 2m synthesis and cytokine release, exceeding that seen after contact activation in the absence of serum. Inactivated serum or serum deficient in C8 did not increase beta 2m production, indicating that the additional activation was due to complement C5b-9. The results suggest that there are two cuprophan-related mechanisms of cell activation: one by contact of cells with the membrane, the other by the complement activation products. Both might synergistically contribute to an increased beta 2m synthesis in hemodialysis patients. PMID- 8465820 TI - A prospective comparative study of continuous arteriovenous hemodiafiltration and continuous venovenous hemodiafiltration in critically ill patients. AB - We have prospectively studied and compared two consecutive groups of critically ill patients treated with either continuous arteriovenous hemodiafiltration (CAVHD) (n = 28) or continuous venovenous hemodiafiltration (CVVHD) (n = 25) to establish the technique of choice. The two groups were comparable in mean age (59 v 58 years), mean Acute Physiology and Chronic Health Evaluation (APACHE) II score (29.6 v 27.4, P = NS), requirements for inotropic drugs, and mean number of failing organs (2.9 v 3.2). CVVHD led to a greater amount of hourly ultrafiltrate (mean, 590 v 424 mL; P < 0.001), but urea and creatinine clearances were not significantly different with the two techniques. Twelve patients survived in the CAVHD group (42.8%) and 13 in the CVVHD group (52%; P = NS). The major advantage for CVVHD use was the substantial decrease in the number of access-related complications (2 v 10; P < 0.025). We conclude that while CVVHD does not offer a significant increase in solute clearance, it significantly minimizes vascular access-related morbidity and should therefore be regarded as the therapeutic modality of choice. PMID- 8465821 TI - The effect of dialyzer reprocessing on performance and beta 2-microglobulin removal using polysulfone membranes. AB - Increased biocompatibility and lower cost are the two major arguments favoring routine dialyzer reprocessing. The impact of longer-term reprocessing is critical to the practical use of polysulfone membranes (PMs), because of the possibility of decreasing efficiency and performance, especially in the removal of beta 2 microglobulin (beta 2M), a protein that has been implicated in the development of dialysis-associated amyloidosis (DDA). In this study, we examine urea clearance (Kd), urea mass transfer coefficient (h0), ultrafiltration coefficient (K(uf)), and percent removal of beta 2M up to 24 uses. The study involved 11 patients on hemodialysis for 5.27 +/- 4.6 years, with a mean age of 62.5 +/- 9.7 years and average run-time treatment of 2.78 +/- 0.3 hours. PMs were tested after being reprocessed manually using bleach and formaldehyde. The efficacy of the dialyzer was examined on uses 1, 5, 10, 15, 20, and 24, and the percent removal of beta 2M was determined except in the twentieth use and corrected for ultrafiltration. The Kd obtained through 24 uses showed no significant change, although h0 was significantly increased in the fifteenth use, and K(uf) was significantly increased in the 10th and 20th use (P < 0.05). The percent removal of beta 2M increased significantly from 44.1 +/- 2.8 (mean +/- SEM) in the first use to 59.4 +/- 2.19 (P < 0.05) in the 10th use, and 62.1 +/- 4.07 and 63.1 +/- 4.27 in the 15th and 24th uses, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465822 TI - Biocompatibility of a glucose-polymer-containing peritoneal dialysis fluid. AB - The currently available glucose-containing peritoneal dialysis fluids (PDF), which are all hyperosmolar, are toxic to the cells present in the peritoneal cavity. However, glucose-polymer solutions, being isosmolar, may have improved biocompatibility in this respect. We therefore compared in vitro the effects of PDF containing glucose-polymers with that of glucose solutions on the function of donor granulocytes and monocytes (MN), and on the viability of mesothelial cells. In addition, the function of peritoneal macrophages (PMO) of eight patients was studied in a randomized cross-over setting following intraperitoneal exposure to glucose-polymer-versus glucose-monomer-containing fluid of comparable ultrafiltration capacity. Donor granulocytes, as well as MN, showed significantly better phagocytosis of both Staphylococcus epidermidis and Escherichia coli after incubation in the glucose-polymer solution as compared with the 3.86% glucose containing fluid. Their oxidative metabolism, as measured by chemiluminescence, also showed that the glucose-polymer solution was less inhibitory than fluids containing 2.27 or 3.86% glucose. Patient-derived PMO showed a significantly better phagocytic capacity for S epidermidis and E coli, a significantly higher killing of E coli, and a significantly higher chemiluminescence response after intraperitoneal exposure to the glucose-polymer solution as compared with the glucose-monomer-based fluid. Increasing the osmolality of the glucose-polymer solution to that of the respective glucose solutions blunted the favorable effect on phagocyte function, suggesting the beneficial effect to be osmolality mediated. However, no major difference was observed between the glucose-polymer solution and the glucose-based fluid in their effects on mesothelial viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465823 TI - Determinants of oxalate balance in patients on chronic peritoneal dialysis. AB - We assessed plasma levels and removal rates of oxalate in 24 patients on chronic peritoneal dialysis (CPD) for oxalosis-unrelated renal failure. The ion chromatographic (IC) measurements of oxalate in plasma, dialysate, and urine (in seven patients with residual renal function) were used to calculate peritoneal and renal clearances of oxalate. The serum state of saturation with calcium oxalate was calculated by means of a computer-based model system. Patient data were compared with those from 19 healthy individuals. Peritoneal clearance of oxalate was 6.3 +/- 4.7 mL/min, ie, 8% of the normal renal clearance. As a result, both plasma oxalate and calcium oxalate saturation were higher than in controls and did not overlap. Plasma was supersaturated with calcium oxalate in only two of 24 patients (8%). Removal of oxalate by dialysis was related to the amount of fluid infused. Overall removal of oxalate (dialysate plus urine) was similar to 24-hour excretion of normal subjects and was taken as a measure of its generation. Oxalate generation rate was dependent on protein (whole and animal) intake, but not on caloric intake or pyridoxine status. Pyridoxine supplementation, 75 and 300 mg daily for 1 months, was not effective in reducing plasma levels or generation rates of oxalate. Residual renal function had a minor influence on oxalate patterns. We conclude that current programs are adequate to maintain oxalate balance in patients on CPD under basic conditions. PMID- 8465824 TI - Advantages of donor-specific blood transfusion in the rat via the portal vein for renal transplantation. AB - It is well known that blood transfusion can promote immune unresponsiveness to a renal allograft in both animals and humans. The present study examined the differences between either portal venous (PV) or intravenous (IV) donor-specific transfusion (DST) alone on the survival of rat renal allografts without other immunosuppression. Seven days before LEW (RT1(1)) renal transplantation, recipient WKA rats (RT1u) were inoculated with graded doses (1.0 to 0.0001 mL) of LEW whole blood through either the portal vein or the tail vein. A dose of 0.001 mL whole blood PV resulted in significantly greater prolongation of renal allograft survival than occurred with IV preimmunization (38.5 +/- 10.6 days v 12.5 +/- 2.7 days). Although recipient survival was not significantly different for the two routes for a lower dose (0.1 mL) of whole blood preimmunization 7 days before transplantation, azotemia and rejection were prevented when the PV route, but not the IV route, was used. However, when 0.1 mL of whole blood was administered 5 days before transplantation, survival was prolonged only in animals preimmunized by the PV route (54.7 +/- 14.0 days v 14.3 +/- 4.0 days). In the stronger reciprocal combination of WKA to LEW, there was an advantage of PV with 0.1 mL whole blood, but not with 1 mL. These results indicate that the beneficial effects of DST on renal allograft survival can be obtained when a smaller volume of blood is given via the PV rather than the IV route and a shorter interval elapses between preimmunization and transplantation. PMID- 8465825 TI - Treatment of hyponatremia: a quantitative analysis. AB - The bulk of clinical and experimental evidence seems to support the view that a catastrophic outcome can accompany rapid correction of chronic hyponatremia. However, the dilemma that faces the clinicians is controlling the rate at which the serum sodium concentration is increased during the treatment of hyponatremia. We present a case of severe hyponatremia and hypokalemia to illustrate, in a quantitative fashion, that the increase in serum sodium concentration will be determined not only by the tonicity of infused fluids, but also, and to a major degree, by the rate of excretion of free water by the kidney. A rapid increase in serum sodium concentration would occur if antidiuretic hormone (ADH) release is inhibited and water diuresis ensues. We suggest that the administration of potassium chloride (orally or via a central line) would have been the appropriate therapy for this patient. PMID- 8465826 TI - Transient syndrome of inappropriate antidiuretic hormone secretion during pregnancy. AB - Plasma osmolality normally decreases in early pregnancy, reaching a minimum at approximately 10 weeks and remaining depressed until term. This is associated with a mean decrease of 4 mEq/L in the plasma sodium level, and with an altered threshold for arginine vasopressin (AVP) release and for thirst. We describe a patient who developed more severe hyponatremia (120 mEq/L), which accompanied the development of hypertension and edema at 37 weeks in her fourth pregnancy. Hyponatremia and hypo-osmolality were associated with marked elevation of the plasma AVP level. The hyponatremia and elevated AVP level resolved after the delivery of the infant. To our knowledge, this is the first reported example of transient inappropriate antidiuretic hormone secretion (SIADH) associated with pregnancy. PMID- 8465827 TI - Posthysteroscopy fungal peritonitis in a patient on continuous ambulatory peritoneal dialysis. AB - We report the first case of posthysteroscopy fungal peritonitis, which developed in a woman 11 days after she had a hysteroscopy for menorrhagia. A high vaginal swab grew Candida albicans and the same organism was cultured from the peritoneal dialysate effluent. A vaginoperitoneal communication was suspected to allow the distension medium to carry the fungus into the peritoneum. The potential use of a prophylactic local antifungal agent before hysteroscopy is discussed. PMID- 8465828 TI - Central venous hemodialysis catheters. PMID- 8465829 TI - L-arginine and progressive glomerulosclerosis. PMID- 8465830 TI - The bioanthropological context of disease. AB - Apparent differences in susceptibility to disease continue to be major delineators between human groups. From the vantage of human evolutionary biology, disease is the biocultural product of the interactions of human biology, culture, and ecology. These interactions are graphically represented in a working model and the characteristics of their interactions are discussed. The variability observed in contemporary African Americans is seen as having its roots in Africa and in the collective history of human origins. Thus, identifying simple factors contributing to disease susceptibilities in African Americans is considerably problematic given the high rate of inherent heterogeneity in this group and their retention and expression of various African ecogenetic variants. By focusing more intensively on comparisons among "US blacks," researchers may be able to better identify specific anatomic, physiochemical, or molecular "markers" that will clarify the diversity in clinical response of many African Americans to disease. PMID- 8465831 TI - Epidemiologic analysis of existing data to investigate hypertensive renal disease: an example from the Maryland End-Stage Renal Disease Registry. AB - Observational epidemiology provides powerful methods for studying the etiology and natural history of renal disease in populations. Existing data sets can be used in the conduct of cross-sectional, case-control, and cohort studies that complement experimental investigations. Analysis of existing data sets is extremely efficient and, in many instances, provides results of similar quality to those derived from studies that depend on the collection of original data. A study based on linkage of hypertensive end-stage renal disease (ESRD) incidence rates from the Maryland Regional ESRD Registry with corresponding prevalence data from a state-wide survey of cardiovascular risk factors (The Maryland Statewide Household Hypertension Survey) illustrates the power, efficiency, and flexibility of observational epidemiologic methods in investigating racial differences in hypertensive ESRD. Such analyses can both test previously established hypotheses and generate new hypotheses for subsequent investigation. PMID- 8465833 TI - The health of African Americans: special emphasis on kidney disease. PMID- 8465832 TI - Hypertensive end-stage renal disease in blacks: the role of end-stage renal disease surveillance. AB - The end-stage renal disease (ESRD) networks and the United States Renal Data System recently have described the epidemiology of ESRD and broadened our appreciation of the impact of ESRD in the United States. This surveillance system also can be used to study the occurrence and control of ESRD. Among the epidemiologic study designs available to conduct research on the etiology of renal failure, case-control studies are uniquely suited for this purpose. The case of hypertensive ESRD illustrates this concept; risk factors for hypertensive ESRD, as a hypothetical exposure in case-control studies, are briefly described. Case-control studies are an efficient and readily used means to study causes of renal failure. PMID- 8465834 TI - Ethnicity and renal disease: lessons from the Multiple Risk Factor Intervention Trial and the Treatment of Mild Hypertension Study. AB - Hypertension, particularly severe hypertension, has proven to be a risk factor for renal disease. Whether the relationship of blood pressure (BP) and high renal disease exists across a wide range of BP levels has been less clear. Compared with whites, blacks have a higher rate of end-stage renal disease from a multiplicity of causes, including hypertension, most prominently in younger age groups. To examine ethnic patterns of renal disease across BPs spanning the range of "normal" to "elevated," data were summarized from three large studies: (1) 12 year mortality for the 347,978 men (22,471 black and 325,507 white) without prior myocardia infarction (MI) screened for the Multiple Risk Factor Intervention Trial (MRFIT) who have been followed an average of 12 years for cause-specific mortality, (2) the baseline and 6-year change in renal function in 5,524 hypertensive men (463 black and 5,061 white) randomized in the MRFIT, and (3) the baseline and 1-year change in creatinine level are compared in 902 black and white men and women (177 black and 725 white) with mild hypertension in the Treatment of Mild Hypertension Study (TOMHS). In the MRFIT screenees, there was a monotonic increase in the risk of renal mortality at higher BP levels, even within the "normal range," both in black and white men. Blacks had higher baseline creatinine levels in both the MRFIT and TOMHS. In the MRFIT hypertensive patients, 6-year change in creatinine predicts coronary heart disease and all cause mortality while the baseline creatinine level did not. Comparisons of randomized groups in the MRFIT or TOMHS did not demonstrate improved renal function with more aggressive BP lowering, but in MRFIT average on-treatment DBP < 95 mm Hg was associated with more favorable slopes of reciprocal creatinine. At 1 year, no gender-specific ethnic differences in creatinine change were observed in TOMHS. In the MRFIT hypertensive men, 6-year creatinine change was slightly more favorable in white men than in black men (-0.088 mumol/l v +3.09 mumol/L, P = 0.004). These data demonstrate (1) a graded and continuous relationship between BP and renal disease in blacks and whites across a wide BP range, (2) that creatinine change predicts subsequent mortality, at least in hypertensive men treated with diuretic-based pharmacologic regimen, and (3) possibly different pattern of creatinine change in response to antihypertensive drug therapy in blacks and whites. PMID- 8465835 TI - Racial differences in renal sodium excretion: relationship to hypertension. AB - Black Americans are more susceptible to hypertension and to renal disease than white Americans. Both normotensive and hypertensive blacks are more apt to have salt-sensitive blood pressure responses to the challenge of a salt load than whites. Moreover, salt sensitivity of blood pressure in both normotensive and hypertensive subjects is associated with a decreased excretory capacity for sodium, implicating the kidney in this phenomenon. Salt sensitivity of blood pressure also is associated with increasing age and, in normotensive subjects, may predict the subsequent development of hypertension. Radical differences in a variety of humoral as well as hemodynamic responses to physical and mental stressors have been identified. The relationships between these observations and renal sodium handling require further investigation. PMID- 8465836 TI - Ethnic differences in cellular ions and transport. PMID- 8465837 TI - Essential hypertension in blacks: is it a metabolic disorder? PMID- 8465838 TI - Kidney disease and hypertension in blacks: scope of the problem. PMID- 8465840 TI - Aase syndrome: novel radiographic features. AB - We report on a female with hypoplastic anemia and abnormally digitalized thumbs who presented with growth failure and novel osseous radiologic abnormalities. In addition to thumb anomalies, abnormalities of the clavicles, ilia, distal sacrum, and coccyx and described. PMID- 8465839 TI - Hyperfiltration and conservation of renal function in hypertensive nephrosclerosis patients. AB - Renal glomerular hyperfiltration has been proposed as an important contributing factor to the progression of hypertensive nephrosclerosis in rats with reduced renal mass. However, no clinical studies have assessed the role of glomerular hyperfiltration in the pathogenesis of hypertensive nephrosclerosis in humans. In a prospective, randomized, long-term blood pressure control study with up to 3 years follow-up, we showed that good blood pressure control with a mean diastolic blood pressure < or = 95 mm Hg preceded by a 2- to 4-month period of diastolic blood pressure < or = 80 mm Hg improved renal function in hypertensive nephrosclerosis patients. Patients treated with minoxidil, an angiotensin converting enzyme inhibitor (enalapril), or a calcium entry blocker (nifedipine) had improvement in renal function, as indicated by a positive slope of the reciprocal serum-creatine concentration versus time and an increment in glomerular filtration rate. These results suggested that improvement in renal function occurred with these major types of antihypertensive drug treatment. To assess the renal hemodynamics of minoxidil, enalapril, and nifedipine, eight patients with hypertensive nephrosclerosis were admitted to the General Clinical Research Center for renal clearance studies on each drug while ingesting a fixed calorie, 12% protein, 40% fat, and 100 mEq Na/d diet. Mean blood pressure, effective renal plasma flow, and renal vascular resistance did not change during the three phases of treatment. However, minoxidil treatment increased the glomerular filtration rate by 48% versus enalapril and by 79% versus nifedipine. Since minoxidil treatment improves renal function while causing a relative hyperfiltration, glomerular hyperfiltration per se is an unlikely mechanism for the progression of hypertensive nephrosclerosis in humans. PMID- 8465841 TI - Brachymesomelia and Peters anomaly: a new syndrome. AB - We report on a child with an unusual mesomelic bone dysplasia and Peters anomaly. While there is some resemblance to the radiographic findings and corneal clouding described by Pillay in the OMMD (ophthalmomandibulo-melic dysplasia) syndrome, there are also differences. The several syndromes that combine brachymesomelia and corneal clouding are discussed. PMID- 8465842 TI - Segregation analysis of hypospadias: a reanalysis of published pedigree data. AB - Little is known about the cause of hypospadias, one of the most common urogenital anomalies in males. Familial clustering of hypospadias is well recognized, with heritability estimated to be about 70% under a simple multifactorial threshold model. Neither alternative genetic mechanisms nor shared environmental factors within families have been explored fully. To learn more about possible genetic mechanisms, we used 2 methods of segregation analysis to analyze a set of published family data. These analyses are based on the families of 103 probands with hypospadias, who were ascertained through surgery departments in Denmark [Sorensen, 1953]. Urogenital examinations were performed on 95% (n = 1,510) of available male relatives, and 2.2% were found to have hypospadias. Within the probands' nuclear families, 12% of nonproband sons of normal fathers were affected. Using the mixed model of inheritance, both the autosomal dominant (AD) and codominant models fit these data better than either autosomal recessive (AR) or multifactorial models. Using the regressive logistic models, both AD and AR models were equally likely, and a model of nonMendelian sibship clustering gave a better fit to these data. These inconsistent findings illustrate the difficulties commonly encountered in segregation analysis. Using 2 different statistical approaches, we found 2 different explanations, both of which differ from the autosomal recessive model originally suggested by Sorensen [1953]. Hypospadias in these families is almost certainly heterogeneous. Determining the cause of familial clustering of hypospadias will require careful delineation of persons with recognized syndromes from uncomplicated cases and detailed information on potential prenatal risk factors. PMID- 8465843 TI - Axial mesodermal dysplasia spectrum. AB - We report on a 4-month-old boy with manifestations of both the oculo auriculovertebral spectrum and the caudal regression sequence. He has preauricular appendages, thoracic and lumbar hemivertebrae, anomalies of the ribs, dextrocardia, sacral "dysplasia," dislocated hips, bilateral talipes equinovarus, imperforate anus, recto-vesical fistula, malformed scrotum, and undescended testes. As suggested by Russell et al. [1981], who reported a patient with similar anomalies, the spectrum of anomalies probably is due to a generalized alteration in mesodermal cell migration during the primitive streak period. The term "axial mesodermal dysplasia spectrum" best describes the widespread anomalies in the cranial and caudal regions. PMID- 8465844 TI - Photoanthropometric study of facial growth in Noonan syndrome. AB - We present a photoanthropometric analysis of 104 individuals with Noonan syndrome. The study contained 53 males and 51 females with an age range of one to 60 years (mean 13.8 years). The results provide an objective evaluation of facial abnormality in Noonan syndrome. Individuals with Noonan syndrome are demonstrated to have an increased mid face height, hypertelorism, retrognathia, a lower nasal bridge and nasal root, a wider mouth, a more prominent upper lip, and apparently lower set ears than normal control individuals. Within the patient group an apparent alteration of facial structure was noted with increasing age, suggesting that remodelling of the characteristic face in Noonan syndrome may occur into adult life. PMID- 8465845 TI - Genetic counselling in Noonan syndrome. AB - A clinical and echocardiographic study is presented of 117 families with Noonan syndrome. The 117 families contained 144 individuals with typical Noonan syndrome. The age range of these individuals was from one week to 45 years (mean 12.0 years). One parent was definitely affected with Noonan syndrome in only 14% of the 117 families (mother 11%, father 3%). In a further 31% of families, one parent had possible signs of Noonan syndrome, based on facial appearance only. Within the apparently sporadic group of probands there was no evidence of increased parental age. Echocardiography demonstrated no cases of subclinical cardiac disease in all first degree relatives examined, and clinical examination alone missed no case of cardiac disease. Segregation analysis of affected pedigrees confirmed autosomal dominant inheritance. If both parents had only possible or no signs of Noonan syndrome, subsequent to the birth of the first child with Noonan syndrome in a family, an empiric recurrence risk of 5% was obtained. PMID- 8465846 TI - Confirmation of a particular but nonspecific metacarpophalangeal pattern profile in patients with the Smith-Magenis syndrome due to interstitial deletion of 17p. PMID- 8465847 TI - Eye abnormalities in the Smith-Magenis contiguous gene deletion syndrome. AB - We present the results of ophthalmologic assessment in 10 patients with interstitial chromosome deletions of 17p11.2, otherwise known as the Smith Magenis syndrome (SMS). The most common abnormalities noted were strabismus, Brushfield spots, high myopia, and retinal detachments. We have previously reported high myopia and retinal detachments in 6 patients with SMS (Finucane et al.: Am J Hum Genet 49:262A, 1991). We present additional details on these individuals, as well as findings in 4 newly reported patients. Ocular pathology appears to be very common in SMS, significantly contributing to disability in people with this syndrome. The combination of high myopia, self-injurious head banging, aggression, and hyperactivity among these patients makes them particularly susceptible to retinal detachments. Detailed ophthalmologic assessment should be included in the clinical work-up and monitoring of all patients with SMS resulting from deletion 17p11.2. PMID- 8465848 TI - Mosaicism for deletion 17p11.2 in a boy with the Smith-Magenis syndrome. AB - We describe a 14-year-old boy with physical and behavioral manifestations of the Smith-Magenis syndrome. Low level mosaicism (11%) for deletion 17p11.2 was found in peripheral blood lymphocytes. The deletion was also observed in 100% of metaphases examined from skin fibroblast cultures. We confirm that the Smith Magenis syndrome is associated with a highly recognizable phenotype. Because evidence of the abnormal cell line may be minimal or absent in peripheral blood, fibroblast studies are indicated for patients in whom mosaicism for deletion 17p11.2 is suspected clinically. PMID- 8465849 TI - Tricho-rhino-phalangeal syndrome type I (TRP I) due to an apparently balanced translocation involving 8q24. AB - Tricho-rhino-phalangeal (TRP) syndromes type I and II are caused by a defective gene located on chromosome 8q24.1. We report a family with 2 sibs affected with TRP type I in combination with an apparently balanced chromosome (8;18) translocation involving 8q24.11. It is very likely that the 8q24 translocation breakpoint is physically linked to the TRP gene(s), thereby facilitating future efforts to clone the TRP gene(s). PMID- 8465850 TI - Duplication of 9q12-q33: a case report and implications for the dup(9q) syndrome. AB - We report on a boy with a direct tandem duplication of 9(q12-q33) and dolichocephaly, beaked nose with prominent philtrum, deep-set eyes, receding small chin, failure to thrive, developmental delay, simian creases, long fingers, stiff joints, and hypoplastic scrotum. This patient is compared to the 5 other reported cases with pure partial dup(9q), and the "trisomy 9q syndrome" described by Turleau et al. [1975]. PMID- 8465851 TI - Dysspondylochondromatosis. AB - We report on 3 unrelated patients with an unusual form of neonatal dwarfism with unequal limb length. Radiographs show multiple enchondromatosis of the tubular and the flat bones and severe segmentation abnormalities of the vertebral column. These observations differ from the hitherto described forms of multiple enchondromatosis with growth disorders of the spine, spondyloenchondroplasia, and others. Therefore we propose to delineate this disorder as a new entity. PMID- 8465852 TI - Familial cases of gastroschisis in a population-based registry. AB - Only a few familial cases of gastroschisis have been reported. Consequently, the risk of a recurrence has been thought to be very small. In a population-based study of gastroschisis that included an extended pedigree of all probands, 6 (4.7%) out of 127 families had more than one affected relative. The relationships of the affected were: sib, half-sib (2), first cousin, second cousin once removed, and great uncle. Sib recurrence was 3.5%. Our results suggest that pregnancies occurring in a family with a history of gastroschisis may be at higher risk of recurrence than previously thought. PMID- 8465853 TI - Are the wolffian anomalies in males the phenotype corresponding to the mullerian anomalies in females? AB - The Wolffian and Mullerian ducts are embryologically closely related. This survey was aimed to determine whether, as has been suggested, Wolffian duct anomalies in males are the phenotype corresponding to Mullerian anomalies in females. This was done by analysis of the phenotype of the males in associations and syndromes in which Mullerian duct anomalies are frequent, and of the phenotype of the females in families in which anomalies of the Wolffian ducts are found. It appears that the only relation between the 2 types of defects seems to be a developmental one. In cases of early insult, anomalies are seen in males and females (e.g., in the association of renal agenesis with Mullerian or Wolffian defects). On the other hand, in all the other associations or syndromes, no relation was observed. This suggests that Wolffian anomalies in males are not the phenotype corresponding to Mullerian anomalies in females. PMID- 8465854 TI - Skeletal histopathology in fetuses with chondroectodermal dysplasia (Ellis-van Creveld syndrome). AB - Chondroectodermal dysplasia (CED) is an uncommon autosomal recessive disorder and one of the short rib polydactyly syndromes (SRPS). It is characterized by acromelic and mesomelic shortness of limbs, postaxial polydactyly, small chest, ectodermal dysplasia, and in many cases, congenital heart defects. Controversy exists over possible changes in the growth plate. With the advent of ultrasonographic examination, increasing numbers of fetuses with osteochondrodysplasias are examined by pathologists. Since histopathologic examination of the skeletal system is useful in defining various osteochondrodysplasias and it has not been described in the fetus with CED, we herein describe 3 cases of fetal CED with emphasis on skeletal histopathology. All 3 pregnancies were terminated at 22-23 weeks because of ultrasonographic demonstration of short limbs and growth retardation. Radiologically, each fetus had acromelic and mesomelic shortness of long bones with smooth round metaphyses, vertically short iliac bones, short ribs and normal vertebrae. These findings are similar to those described in the larger newborn infant with CED. Histopathologically, the cartilage of the long bones showed chondrocytic disorganization in the physeal growth zone. The findings are dissimilar to those of larger infants and older children in whom chondrocytic columnization has been seen in the central physis and disorganization in peripheral physis. Furthermore, a variable degree of chondrocytic disorganization was also seen in the central physeal growth zone of vertebrae in these fetuses. Other findings noted at fetopsy were: polydactyly in all 3 cases, congenital heart defect in 2 and an abnormal frenulum in one case. The foregoing phenotypic and radiographic manifestations and skeletal histopathology help separate CED from other SRPS. PMID- 8465855 TI - Protein-losing gastroenteropathy with facial anomaly and growth retardation: a mild case of Hennekam syndrome. AB - A 7-year-old boy with a peculiar face, protein-losing gastroenteropathy and growth retardation is reported. Although he has a face similar to those 5 cases reported previously by Hennekam et al. (Am J Med Genet 34:593-600, 1989) and Gabrielli et al. (Am J Med Genet 40:244-247, 1991), he is not mentally retarded nor does he have severe lymphedema. This patient seems to have a mild case of the Hennekam syndrome. PMID- 8465856 TI - Otopalatodigital syndrome type II associated with omphalocele: report of three cases. AB - We present 3 patients with otopalatodigital (OPD) syndrome type II and omphalocele; 2 of the cases are brothers. There are now 6 known cases of OPD type I or II with omphalocele. We propose that this combination is not coincidental and discuss mechanisms that may result in the combination of OPD, omphalocele, and other midline defects. PMID- 8465857 TI - Further delineation of spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, with emphasis on diagnostic features. AB - Further delineation of a generalized bone dysplasia which we call spondylo-meta epiphyseal dysplasia, short limb-abnormal calcification type is presented. This dwarfing condition has several serious complications, with the most common cause of death being spinal cord damage secondary to atlantoaxial instability. It is a heritable condition with an autosomal recessive mode of transmission. Radiologic diagnostic criteria are developed on the basis of studies in 8 patients with the oldest being between 4 and 5 years old. The condition is clinically and radiographically apparent neonatally or in early infancy, and it is probable that all or almost all affected individuals will come to medical attention in the age range screened by this study. PMID- 8465858 TI - Multiple epiphyseal dysplasia, Fairbank type: morphologic and biochemical study of cartilage. AB - We have performed histochemical, immunohistochemical, electron microscopic, and biochemical studies on the upper tibial cartilage from a case of multiple epiphyseal dysplasia, Fairbank type. Most chondrocytes had intracytoplasmic inclusions which took the stains for proteins and were resistant to microbial collagenase digestion. The electron microscopic study showed that the inclusions are dilatations of the rough endoplasmic reticulum containing a material with alternately wide electron dense and electron lucent layers. Both in optical and in electron microscopy the inclusions fixed antibodies against the core protein of the large cartilage proteoglycans (aggrecans). They didn't stain with antibodies against type II collagen. The gel electrophoretic pattern of the large proteoglycans was different from normal controls. The morphologic and biochemical alterations found in multiple epiphyseal dysplasia are similar to those already described in pseudoachondroplasia (Stanescu et al.: Eur J Pediatr 138:121-225, 1982; Stanescu et al.: J Bone Joint Surg 66A:817-836, 1984). However, the inclusions are smaller and the growth cartilage much less disorganized in multiple epiphyseal dysplasia. The similarity of morphologic and biochemical abnormalities strongly suggests that the two diseases have a similar pathogenesis and belong to the same bone dysplasia family. PMID- 8465859 TI - Unusual lymphangioma observed prenatally in a 45,X fetus. AB - We present a case of a large frontal lesion, suspected on antenatal ultrasound to be a cephalocele. The cardiac anatomy was abnormal and fetal blood sampling showed a 45,X chromosome constitution. Postmortem examination proved this to be a lymphangioma and confirmed the presence of a cardiac defect. We suggest that this lymphangioma represents an unusual manifestation of monosomy X and discuss the importance of doing chromosome analysis in the presence of such a lesion which is of similar appearance as a cephalocele. PMID- 8465860 TI - New autosomal recessive lethal disorder with polycystic kidneys type Potter I, characteristic face, microcephaly, brachymelia, and congenital heart defects. AB - We report on 3 pairs of sibs from unrelated families, who present with polycystic kidneys Potter type I claimed to be specific for the ARPKD, and with microbrachycephaly, hypertelorism with telecanthus, large posteriorly angulated fleshy ears and various congenital malformations including congenital heart defects. We suggest that they represent a previously unrecognized autosomal recessive lethal developmental disorder within the group of infantile polycystic kidney disease and Potter sequence. PMID- 8465861 TI - Further delineation of the Baller-Gerold syndrome. AB - Three new patients with the Baller-Gerold syndrome bring the number of reported cases to 20. In addition to craniosynostosis involving various sutures and preaxial reduction defects of variable severity, affected patients may have anal, urogenital, cardiac, central nervous system, and vertebral defects. Autosomal recessive inheritance is supported by the presence of affected sibs and parental consanguinity. PMID- 8465862 TI - Morfan: a new syndrome characterized by mental retardation, pre- and postnatal overgrowth, remarkable face and acanthosis nigricans in 5-year-old boy. PMID- 8465863 TI - Limb deficiencies and chorion villus sampling. PMID- 8465864 TI - Hereditary erythermalgia and acquired erythromelalgia. PMID- 8465865 TI - X-linked mental retardation with agenesis of the corpus callosum. PMID- 8465866 TI - Confirmation of the mandibulofacial dysostosis, Toriello type. PMID- 8465867 TI - Waardenburg syndrome and spina bifida. PMID- 8465868 TI - Cigarette smoking: implications for psychiatric illness. AB - Psychiatry has been essentially uninterested in cigarette smoking and nicotine. However, it is the view of this author that both cigarette smoking and smoking cessation are highly relevant to the clinical psychiatrist in the care of patients and that they are potentially a source of important insights into psychopathology. To support that view, the author reviews the evidence that both major depression and depressive symptoms are associated with a high rate of cigarette smoking and that lifetime history of major depression has an adverse impact on smoking cessation. He also reviews the data available on the influence of cigarette smoking cessation on the course of major depression, the relationship between cigarette smoking and other psychiatric diagnoses, particularly schizophrenia, and the neuropharmacology that might underlie these associations. Finally, the implications of these relationships for psychiatry are discussed. PMID- 8465869 TI - Help-seeking pathways: a unifying concept in mental health care. AB - The authors argue that the concept of help-seeking pathways, defined generically, oriented toward institutional structures, and put at the forefront of research, can help integrate much of what we know about the use of mental health care and how to make such care more accessible and effective among underserved populations. They focus the concept of help-seeking pathways on current issues and research findings pertinent to the onset of psychological distress, the contacting of mental health care facilities, and treatment in such facilities. Pathways are not random; they are structured by the convergence of psychosocial and cultural factors and have sufficient integrity to be studied directly as unfolding processes. PMID- 8465870 TI - Loss of drug effects during continuation therapy. AB - OBJECTIVE: This study sought to determine what proportion of relapses during continuation therapy with antidepressants can be attributed to loss of nonspecific placebo effects while the patients are taking the drugs. METHOD: Depressed patients were studied over a 12-week period. One hundred sixty-four patients were randomly assigned to placebo, 174 to imipramine, and 169 to phenelzine. At 6 weeks 35 were judged to be responders to placebo, 70 to imipramine, and 96 to phenelzine. These patients continued their double-blind treatment for weeks 7-12. RESULTS: Thirty-one percent of the patients who were taking placebo, approximately 12% who were taking imipramine, and approximately 9% who were taking phenelzine relapsed in the 7- to 12-week phase. Two different methods of estimating relapses suggested that during the first 3 months of treatment, a large percentage of the relapses of patients taking drugs was attributable to the loss of nonspecific placebo effects rather than true drug effects. CONCLUSIONS: A considerable proportion of relapses in the first 3 months of treatment with antidepressants appears to be due to loss of placebo effects. These clinically relevant data may be used to encourage patients who relapse during this period, and who erroneously conclude that anti-depressant effects are temporary, to try another medication. PMID- 8465871 TI - Further evidence that a placebo response to antidepressants can be identified. AB - OBJECTIVE: The authors' goal was to analyze the acute phase of antidepressant drug treatment to identify placebo responses. METHOD: Patients rated as improved after 6 weeks of double-blind treatment with imipramine or phenelzine were followed for an additional 6 weeks of double-blind treatment. Initial responses were classified according to the speed of improvement (abrupt or gradual), the persistence or nonpersistence of improvement, and the timing of improvement (early or late onset). RESULTS: It was predicted that patients with nonpersistent, abrupt responses to the drugs were actually experiencing a placebo response and would have the worst prognosis. In fact, this group accounted for a disproportionate number of the relapses. Nonpersistent responders to a drug had a 23.7% relapse rate, but persistent responders had only a 9.0% relapse rate, a significant difference. CONCLUSIONS: The authors conclude that a significant proportion of relapses within the first 6 weeks of treatment with an active drug are not related to loss of a true drug effect. Rather, some are related to loss of nonspecific placebo effects, and abrupt nonpersistent responses during drug treatment are most likely the result of placebo effects. PMID- 8465872 TI - Trends in the prescription of antidepressants by office-based psychiatrists. AB - OBJECTIVE: This study was done in an effort to determine whether there was a change over the past decade in the number and proportion of patients prescribed antidepressants by psychiatrists in private practice. METHOD: The authors analyzed data from the National Ambulatory Medical Care Survey for the years 1980, 1985, and 1989, focusing on visits by adults over the age of 18 years to physicians specializing in psychiatry and psychiatric subspecialties. RESULTS: The number of visits that included prescribing an antidepressant medication grew from approximately 2.5 million in 1980 to 4.7 million in 1989, or from 17.9% to 30.4% of all office-based psychiatric visits. Fluoxetine, which first became available in 1988, accounted for 29.6% of the prescriptions for antidepressants in 1989. Increases in prescriptions for antidepressants were particularly evident for male patients, young adult patients, and patients with neurotic disorders. CONCLUSIONS: There was an increase in the 1980s in the use of antidepressants in office-based psychiatric practice. The advent of new agents and the broadening of the clinical usefulness of existing agents may have contributed to this increase. PMID- 8465873 TI - Is antisocial personality a valid diagnosis among the homeless? AB - OBJECTIVE: It has been argued that among the homeless many of the features of antisocial personality may be artifacts of homelessness and that strict application of the diagnostic criteria may be insensitive to social and cultural factors in this group. The authors studied a large group of homeless men and women to investigate the appropriateness of the diagnosis of antisocial personality disorder among the homeless. METHOD: Six hundred homeless men and 300 homeless women were randomly selected from shelters and street locations in St. Louis and interviewed with the National Institute of Mental Health Diagnostic Interview Schedule. RESULTS: In this sample of homeless men and women, most, but not all, adult symptoms of antisocial personality disorder were significantly associated with number of childhood conduct disorder symptoms. The onset of symptoms of antisocial personality disorder usually preceded the onset of homelessness. The rates of antisocial personality disorder were not significantly affected by discounting the antisocial disorder symptoms thought to be confounded with homelessness. CONCLUSIONS: Overall, the data support the appropriateness of the diagnosis of antisocial personality disorder among homeless populations. It cannot be said from these data that homelessness often leads to antisocial behaviors. PMID- 8465874 TI - Patients' attitudes toward hallucinations. AB - OBJECTIVE: This study examined patients' attitudes toward their hallucinations by assessing their beliefs about the purposes served by hallucinations and the adverse effects of hallucinations. It also investigated whether these attitudes were related to characteristics of the hallucinations or of the patients, whether the attitudes changed after treatment, and whether attitudes before treatment predicted the presence or absence of hallucinations after treatment. METHOD: Fifty hallucinating psychiatric inpatients were given semistructured interviews shortly after admission to the hospital and again shortly before discharge. The interviews elicited detailed descriptions of 12 phenomenologic characteristics of hallucinations and 11 attitude variables. RESULTS: The majority of subjects reported some positive effects of hallucinations. The presence of olfactory hallucinations and the ability to predict hallucinations were significantly related to valuing hallucinations. Attitudes usually did not change with treatment; when they did change they usually became more positive. Subjects who valued hallucinations more before treatment were significantly more likely to be hallucinating after treatment. CONCLUSIONS: The findings are consistent with the idea that psychological factors contribute to the expression of hallucinations. Assessing adaptive functions of hallucinations may predict whether hallucinations will respond to treatment and identify fruitful areas for psychosocial intervention. PMID- 8465875 TI - Schizophrenic patients' sensitivity to social cues: the role of abstraction. AB - OBJECTIVE: Since individuals with schizophrenia often have difficulty with abstract tasks, they should have more problems recognizing abstract social cues (e.g., inferences regarding actors' affect and goals) than concrete cues (e.g., observations of actors' behavior and dialogue). Moreover, recognition of abstract and concrete cues should interact with the level of emotional arousal engendered by the situation; previous research has shown that schizophrenic patients perform better on cue recognition tasks when the situation produces moderate rather than low levels of arousal. METHOD: These hypotheses were tested in 24 patients with schizophrenia diagnosed according to the DSM-III-R criteria and 15 normal comparison subjects. All subjects viewed eight short vignettes of interpersonal situations that produce low and moderate levels of arousal. They then answered questions representing perception of abstract and concrete cues that had been matched for difficulty and consistency. RESULTS: The schizophrenic patients were significantly less sensitive to interpersonal cues than the normal subjects. The patients were also less sensitive to abstract than to concrete social cues, and for them there was a significant interaction between cue abstraction level and situational arousal. Specifically, the schizophrenic subjects performed worse on the abstract cue recognition task for the low-arousal situations. CONCLUSIONS: Findings regarding the social cue recognition patterns of schizophrenic patients could play an important role in the development of valid measures of social cognition for this population. PMID- 8465876 TI - Separation anxiety in panic disorder. AB - OBJECTIVE: A number of researchers have provided evidence that separation anxiety is an important antecedent or current affect in panic disorder. The objective of this pilot study was to test this hypothesis by comparing dreams, screen memories, and life situations of panic disorder patients with those of comparison patients. METHOD: A recent dream with associations, screen memories with associations, and life situations at onset of symptoms were recorded verbatim during semistructured interviews with 20 patients with DSM-III-R panic disorder and 20 comparison subjects upon referral to a private outpatient practice. A judge blind to the diagnoses rated each of the dreams, screen memories, and life situations separately on each of the 10 Gottschalk-Gleser Content Analysis Scales, thereby measuring manifest and latent death, mutilation, separation, guilt, and shame anxiety and overt and covert hostility in each group. RESULTS: mean separation anxiety scores were significantly higher in both the dreams and screen memories of the panic disorder patients than in the comparison patients. Mean scores for covert hostility directed outward were significantly higher in the dreams of the panic disorder patients than in the comparison patients. CONCLUSIONS: The hypothesis that separation anxiety is a prevalent affective undercurrent in the dreams and screen memories of panic disorder patients was supported. Significantly higher covert hostility in the panic disorder patients' dreams may support Bowlby's observation that people with high separation anxiety tend to disavow their anger. PMID- 8465877 TI - Quality of life and psychiatric morbidity in panic disorder and generalized anxiety disorder. AB - OBJECTIVE: This report examines the impact of panic disorder and/or generalized anxiety disorder on quality of life and the implications of these findings on nosological categories. METHOD: A total of 357 subjects with a current episode of panic disorder and/or generalized anxiety disorder were diagnosed according to DSM-III-R criteria, using structured clinical interviews, as part of a prospective, naturalistic, longitudinal, multicenter study of a clinical population with anxiety disorders. RESULTS: There was a high degree of coexistence of anxiety disorders and major depressive disorder. Subjects with generalized anxiety disorder almost universally had other disorders, were the most likely to have at least one other anxiety disorder or major depressive disorder at intake, had the earliest age at onset, and had the worst emotional health rating. Subjects with panic disorder without agoraphobia had the most likelihood of a history of alcohol abuse. Nine percent of the subjects had a history of suicide attempts or gestures. CONCLUSIONS: The subjects showed significant impairment in quality of life. The highly frequent coexistence of other anxiety disorders with generalized anxiety disorder and the overall lack of differences on many quality of life measures raise questions of nosology, particularly for generalized anxiety disorder. PMID- 8465878 TI - Long-term psychosocial effects of childhood exposure to parental problem drinking. AB - OBJECTIVE: The effects of childhood exposure to parental problem drinking remain unclear because of inconsistent findings and methodologic difficulties in previous studies. The authors used a large community sample to examine whether exposure to parental problem drinking in childhood was related to a greater number of psychiatric symptoms and impaired social and occupational functioning in adulthood. METHOD: The study used self-report data from the Piedmont Health Survey, a project of the Epidemiologic Catchment Area program, which were collected from a stratified random sample of 2,936 adults residing in a five county catchment area in North Carolina. The National Institute of Mental Health Diagnostic Interview Schedule was used to measure the subjects' lifetime psychiatric symptoms. Social and occupational functioning were assessed with two scales measuring social support, a scale measuring occupational prestige, and an occupational problem index. Regression analyses were used to determine whether exposure to parental problem drinking in childhood was associated with adverse psychosocial outcomes in adulthood. RESULTS: Adults who had been exposed to parental problem drinking in childhood were more likely to manifest psychiatric symptoms and marital instability, but they showed no difference from the rest of the sample in occupational functioning. CONCLUSIONS: Exposure to parental problem drinking in childhood is positively associated with specific adverse effects in adulthood even after controlling for other confounding childhood risk factors. PMID- 8465879 TI - Psychiatric complications of family reunion after four decades of separation. AB - OBJECTIVE: After four decades of separation due to civil war, many people who had migrated to Taiwan from mainland China had the unexpected opportunity to briefly visit their families in mainland China. A study was conducted to examine psychiatric complications associated with these family reunions following long involuntary separation. METHOD: Eighty subjects who made the journey were given semistructured interviews investigating their psychological experiences relating to the family reunion. The variables investigated were sociodemographic characteristics, the subject's previsit emotional condition, factors related to the family reunion experience, and stress encountered during the visit. RESULTS: The survey indicated that more than one-fifth of the subjects (22.5%) developed psychiatric complications, mainly depression, immediately after the visit. Determinants found to contribute significantly to the occurrence of emotional disorders were previous ways of expressing homesickness, family members seen during the reunion, family misfortunes that the subjects discovered, family conflict encountered at the reunion, and tactics for coping with such stressors. CONCLUSIONS: The study results suggest that family reunions after long-term separation can be trauma-repairing experiences for some but for others can lead to trauma reexperiencing and psychiatric complications requiring mental health intervention. PMID- 8465880 TI - Psychophysiologic assessment of traumatic imagery in Israeli civilian patients with posttraumatic stress disorder. AB - OBJECTIVE: This study used a script-driven imagery technique, previously used with combat veterans, to assess physiologic responses of Israeli survivors of noncombat traumas. METHOD: Each subject had experienced an event meeting DSM-III R criterion A for posttraumatic stress disorder (PTSD). The subjects were classified on the basis of the full DSM-III-R criteria into a current PTSD group (N = 13) and a non-PTSD group (N = 13). Thirty-second scripts describing each subject's personal traumatic event, as well as other events, were prepared. The scripts incorporated subjective visceral and muscular responses reported to have accompanied each experience. In the laboratory, the scripts were read one at a time to the subject, who was instructed to imagine each event portrayed as vividly as possible, while heart rate, skin conductance, and left lateral frontalis electromyogram levels were measured. RESULTS: Multivariate analysis of variance revealed that the physiologic responses of the PTSD subjects during imagery of their personal traumatic experiences were significantly greater than those of the non-PTSD subjects. This difference was not explained by age, gender, or rated severity of the traumatic event. A physiologic discriminant function derived from previously studied Vietnam veterans correctly classified nine of the 13 PTSD subjects (sensitivity = 69%) and 10 of the 13 non-PTSD subjects (specificity = 77%). CONCLUSIONS: These results replicate previous findings of heightened physiologic responses during personal combat imagery in male American war veterans and extend them to a group of male and female Israeli civilian victims of trauma, supporting the robustness of physiologic responding during personal traumatic imagery as a measure of PTSD. PMID- 8465881 TI - The roles of psychiatrists in organized outpatient mental health settings. AB - OBJECTIVE: This paper describes the clinical roles of psychiatrists in U.S. organized outpatient mental health settings. METHOD: Data were analyzed from the 1986 National Institute of Mental Health Client/Patient Sample Survey. The authors determined the range, volume, and content of services provided to established outpatients treated by psychiatrists at six types of mental health organizations: state and county mental hospital clinics, general hospital mental health clinics, private psychiatric hospital clinics, U.S. Department of Veterans Affairs medical center mental health clinics, free-standing mental health clinics, and multiservice mental health organizations. RESULTS: The psychiatrists treated nearly one-half (48.2%) of the established outpatients in organized settings, more than any other discipline. Most of the psychiatrists' patients (68.3%) were also treated by other mental health professionals. Psychiatrists treated a greater proportion of the patients at hospital-based clinics (60.7%) than at clinics without hospital affiliations (43.6%). They also treated larger proportions of the patients with schizophrenia (77.9%), affective disorders (50.6%), or anxiety disorders (59.2%) than those with adjustment disorders (23.7%), substance use disorders (34.3%), or childhood mental disorders (29.5%). The patients treated by psychiatrists commonly received psychotropic medications (77.3%) and individual therapy (66.3%) but less commonly received group (20.7%), skills (11.9%), or family (5.9%) therapy. CONCLUSIONS: In organized outpatient settings, psychiatrists typically work with other mental health professionals to treat a select group of severely ill patients. However, there is considerable variation in the extent to which different types of mental health organizations rely on psychiatrists to provide clinical care. PMID- 8465882 TI - Course of depression in patients with hypertension, myocardial infarction, or insulin-dependent diabetes. AB - OBJECTIVE: The authors examined the course of depression over 2 years for outpatients with and without a history of hypertension, a history of myocardial infarction, or current insulin-dependent diabetes. METHOD: Among outpatient visitors to the practices of 523 general medical clinicians and mental health specialists, 626 depressed patients were followed for 1 or 2 years with a telephone-administered interview based on the format of the National Institute of Mental Health Diagnostic Interview Schedule. RESULTS: Depressed patients with and without medical illness had high rates of persistent depressive symptoms and spells over 2 years. Patients with a lifetime history of myocardial infarction had significantly more spells of depression over the first follow-up year, more total symptoms of depression in the second follow-up year, and more depressive symptoms at the end of each follow-up year than depressed patients without myocardial infarction. The course of depression did not differ significantly for depressed patients with and without a lifetime history of hypertension or current insulin-dependent diabetes. CONCLUSIONS: Among depressed adult outpatients, a history of myocardial infarction is associated with a particularly poor clinical prognosis. A relatively high percentage of all depressed patients in this study had persistent depression regardless of the extent of medical comorbidity. PMID- 8465883 TI - Psychopathology in younger versus older persons with very mild and mild dementia of the Alzheimer type. AB - OBJECTIVE: The psychopathology associated with early-onset dementia of the Alzheimer type was investigated by comparing the prevalence of psychiatric symptoms in younger subjects (mean age = 59 years) who had very mild or mild dementia with that in older adults (mean age = 72) whose dementia was of equivalent severity. METHOD: Nondemented comparison subjects and persons with very mild or mild dementia of the Alzheimer type were recruited to participate in longitudinal studies. All subjects met strict inclusion and exclusion criteria. Information pertaining to personality changes, affective symptoms, and psychotic symptoms was included in the 90-minute semistructured, physician-administered interview, which was used to assign a clinical dementia rating according to published guidelines. The younger group were age 64 or younger and consisted of 20 nondemented subjects, 11 subjects with very mild dementia, and 18 subjects with mild dementia. The older group, described previously, were 64-83 years old and consisted of 83 nondemented subjects, 41 persons with very mild dementia, and 68 subjects with mild dementia. RESULTS: The psychopathology in the younger subjects was similar to that in the older group. Personality changes occurred in over 80% of the younger persons with very mild illness. Psychotic symptoms were present in over 40% of the younger persons with mild illness but were rare in the group with very mild dementia. CONCLUSIONS: Similar patterns of psychopathology in younger and more elderly persons with dementia of the Alzheimer type support the suggestion that these changes are direct effects of the illness on the CNS. Increased attention to documenting these noncognitive symptoms and studying various treatments is urgently needed. PMID- 8465884 TI - The relationship between dementia and elder abuse. AB - OBJECTIVE: Alzheimer's disease and other dementias may be associated with greater risk for physical abuse than other illnesses of the elderly. The authors examined the relationship between dementia and abusive behavior in a group of demented patients and their caregivers. METHOD: An anonymous questionnaire was distributed to 1,000 caregivers who called a telephone help line specializing in dementia. Demographic characteristics of patients and caregivers were assessed, the occurrence of abuse was examined, and caregivers completed the Zarit Burden Interview and the Zung Self-Rating Depression Scale. RESULTS: Questionnaires were completed by 342 caregivers. The mean age of caregivers was 56.1 years; 163 (54.5%) were adult children caring for parents, 111 (37.1%) cared for spouses, and 25 (8.4%) cared for other relatives. Thirty-three caregivers (11.9%) reported that they had directed physically abusive behavior (e.g., pinching, shoving, biting, kicking, striking) toward the dementia patient in their care. These caregivers had been providing care for more years, cared for patients functioning at a lower level, displayed higher burden scores, and displayed higher depression scores than caregivers who reported no abuse. In addition, 92 caregivers (33.1%) reported that the patient directed abuse toward them during the course of providing care. Caregivers who had been abused by patients, in comparison to those who had not, were more likely to direct abusive behavior back toward the patient in their care. CONCLUSIONS: These results support the hypothesis that abuse involving cognitively impaired older adults and their caregivers may be associated with the relatively high psychological and physical demands placed on family members who care for relatives with dementia. PMID- 8465885 TI - Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. AB - The authors found that buspirone added to the treatment of 33 patients with obsessive-compulsive disorder who were refractory to the serotonin reuptake inhibitor fluvoxamine was no better than placebo in reducing obsessive compulsive, depressive, or anxiety symptoms. This finding suggests that addition of buspirone to ongoing fluvoxamine therapy is not an effective treatment strategy for most patients with obsessive-compulsive disorder. PMID- 8465886 TI - Side effects of light therapy in seasonal affective disorder. AB - The authors report the frequency of side effects of light therapy in 105 patients with seasonal affective disorder treated with three intensities of light. Common symptoms to emerge during treatment were headache (19%), eyestrain (17%), and feeling "wired" (14%). There was no relationship between side effects and intensity of light used. PMID- 8465887 TI - Association of nonsuppression of cortisol on the DST with primary polydipsia in chronic schizophrenia. AB - Thirteen polydipsic and 40 nonpolydipsic chronic schizophrenic patients received the dexamethasone suppression test while stabilized on psychotropic medication regimens. Thirty-eight percent (N = 5) of those with polydipsia but only 5% (N = 2) of those without polydipsia were nonsuppressors of cortisol (i.e., had an abnormal response). It is suggested that hippocampal dysfunction could cause both polydipsia and cortisol dysregulation in these patients. PMID- 8465889 TI - Alexithymia in victims of sexual assault: an effect of repeated traumatization? AB - The authors compared scores on the Toronto Alexithymia Scale of 12 rape victims with PTSD, 12 rape victims without PTSD, and 12 nontraumatized comparison subjects. Rape victims were more alexithymic than were nontraumatized comparison subjects, and subjects with a history of more than one episode of rape were more alexithymic than were subjects with a single episode. PMID- 8465888 TI - Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression. AB - The authors measured CSF concentrations of corticotropin-releasing hormone (CRH) and arginine vasopressin in nine depressed patients before and after fluoxetine treatment. They found significant decreases in CSF CRH, CSF arginine vasopressin, and Hamilton depression ratings. Thus, the therapeutic effect of this serotonin uptake inhibitor may be related to diminution of these arousal-promoting neuropeptides. PMID- 8465890 TI - Continuous infusion of haloperidol. PMID- 8465891 TI - Fetishism and clomipramine. PMID- 8465892 TI - Culture-bound trichotillomania. PMID- 8465893 TI - Salt appetite with psychosis, intermittent hyponatremia, and polydipsia. PMID- 8465894 TI - Methadone dosage, cocaine and opiate abuse. PMID- 8465895 TI - Disulfiram therapy in patients abusing cocaine and alcohol. PMID- 8465896 TI - APA position statement on abortion. PMID- 8465897 TI - APA position statement on abortion. PMID- 8465898 TI - APA position statement on abortion. PMID- 8465899 TI - Competency for execution. PMID- 8465900 TI - Competency for execution. PMID- 8465901 TI - Deja vu and holographic images. PMID- 8465902 TI - Empirical evaluation of the global deterioration scale for staging Alzheimer's disease. PMID- 8465903 TI - Frequency of diagnosis of obsessive-compulsive disorder. PMID- 8465904 TI - Suicide and panic disorder. PMID- 8465905 TI - Efficacy of brief dynamic psychotherapy. PMID- 8465907 TI - The AIDS dilemma. PMID- 8465906 TI - Practice guideline for major depressive disorder in adults. American Psychiatric Association. PMID- 8465908 TI - A review of allograft processing and sterilization techniques and their role in transmission of the human immunodeficiency virus. AB - Human immunodeficiency virus (HIV) infection via vascular organ and tissue transplantation is well documented. The majority of these transmissions occurred before the development of HIV antibody testing, which is now a routine screening tool used before organ and tissue procurement and transplantation. There exists what is commonly referred to as a "window" of seronegativity after HIV infection. Potential donors may be infectious with the HIV virus but not yet detected with available HIV antibody tests. Bone and soft tissue retrieval may be done in either a sterile or clean, nonsterile manner. Deep freezing and freeze-drying (lyophilization) are two commonly used modes of preserving bone and soft tissue allografts. In 1985, a screened donor who was in the window of seronegativity underwent vascular organ and musculoskeletal tissue harvest. The bone and soft tissue procured underwent a variety of processing and preservation techniques. There have been no known cases of HIV transmission from the processed freeze dried tissues. Evidence now exists that early HIV infection, before HIV antibody production, may be the most infectious period. The HIV antigen testing may allow earlier detection of an infectious donor, thus closing the window of seronegativity. It is unknown whether this nontransmission of HIV to the recipients of the processed and freeze-dried tissue was due to the processing or the nature of the tissue itself. PMID- 8465909 TI - A comparison of patellar tendon autograft and allograft used for anterior cruciate ligament reconstruction in the goat model. AB - Similar-sized patellar tendon autografts and fresh-frozen allografts were used to reconstruct the anterior cruciate ligament of one knee in 40 female goats. Evaluations of the reconstructions and contralateral controls at the 6-week and 6 month postoperative periods included anterior-posterior translation, mechanical properties determined during tensile failure tests, measurement of cross sectional area, histology, collagen fibril size and area distribution, and associated articular cartilage degenerative changes. Six months after anterior cruciate ligament reconstruction, the autografts demonstrated a smaller increase in anterior-posterior displacement, values of maximum force to failure two times greater, a significant increase in cross-sectional area, a more rapid loss of large-diameter collagen fibrils, and an increased density and number of small diameter collagen fibrils compared to the allografts. Clinical significance. More surgeons are allowing their patients to return to running and sports 6 months after anterior cruciate ligament reconstruction. While the structural and material properties of autografts and allografts at time zero are similar, in the goat model during the first 6 months they differ. The allografts demonstrate a greater decrease in their implantation structural properties, a slower rate of biologic incorporation, and the prolonged presence of an inflammatory response. At 6 months the autograft demonstrates a more robust biologic response, improved stability, and increased strength to failure values. PMID- 8465910 TI - Arthroscopic treatment of synovial impingement of the ankle. AB - Twenty-nine cases of operative arthroscopy of the ankle were done between 1985 and 1989 for synovial impingement of the ankle. The average age of the patients was 37 years. All patients (17 men, 12 women) reported an earlier history of injury, with 24 of the patients (83%) noting chronic ankle pain after an inversion injury and 5 of the patients (17%) reporting a previous ankle fracture. Physical examination elicited anterolateral tenderness at the ankle in all cases with associated anteromedial pain in 4 patients. A demonstrable "click" was evident in 6 of the patients (21%) on forced dorsiflexion of the ankle. All patients failed conservative treatment including physical therapy and nonsteroidal antiinflammatory drugs. Surgery was performed at an average of 36 months postinjury. Ankle arthroscopy revealed extensive hypertrophic synovial thickening and scar tissue anterolaterally, indicating synovial impingement in all patients. Associated chondromalacia of the distal tibia was seen in 21% of the patients. Operative arthroscopy included partial synovectomy and debridement of the hypertrophic tissue and partial shaving chondroplasty of the tibia when indicated. Postoperatively, patients were weightbearing as tolerated. Results were assessed subjectively and objectively. At 25-month followup 26 patients had excellent or good results and 3 had fair results; there were no poor results. There were no major complications, including infection or neurovascular compromise. The 3 patients with associated ankle instability comprised the "fair" result group and eventually required lateral ankle reconstruction. Thus, chronic ankle pain due to synovial impingement can be safely, predictably, and effectively treated by operative ankle arthroscopy. PMID- 8465911 TI - Experimental muscle strain injury. Early functional and structural deficits and the increased risk for reinjury. AB - The structural and functional strength of a muscle immediately after an experimentally created strain injury was examined to provide clinically relevant information for the early treatment of muscle strain injuries. The extensor digitorum longus muscles of 12 adult male rabbits were studied. Contractile force and shortening, and peak load were determined for control muscles. A nondisruptive strain injury was created by stretching the experimental muscles just short of complete rupture. Contractile force generation and shortening, and peak load were determined after the experimental strain injury. Peak load was 63% and elongation to rupture was 79% for the experimental muscles relative to the controls. Statistically significant lower values for contractile force generation and shortening were also seen in the experimental muscles. Histologic and gross examinations revealed that incomplete disruptions occurred near the distal muscle tendon junction. These experimental data suggest clinical implications, such as 1) a muscle-tendon unit is significantly more susceptible to injury following a strain injury than normal muscle, 2) early return to the uncontrolled environment of athletic competition may place the injured muscle at risk for further injury, and 3) therapeutic regimens designed to achieve an early return to competition may further increase the risk for additional injury by eliminating protective pain mechanisms. Although the decrements in peak load and elongation to failure are less than normal muscle, the values seem high enough to allow mobilization of the injured extremity and functional rehabilitation. PMID- 8465912 TI - Sports and osteoarthrosis of the hip. An epidemiologic study. AB - To investigate if participation in sports increases the risk of developing osteoarthrosis of the hip, we did a case-control study on the sports activities of 233 men (up to age 49) who were recent recipients of a prosthesis because of severe idiopathic osteoarthrosis of the hip and 302 men randomly selected from the general population. Assessments of sports, job history, and health status were made by an interview. Men with high exposure to sports of all kinds combined (in hours) had a relative risk to develop osteoarthrosis of the hip of 4.5 compared to those with low exposure. Track and field sports and racket sports seemed to be the most hazardous to the hip joint. Men who had been exposed to high physical loads both from their occupation and sports had a relative risk of 8.5 to develop osteoarthrosis of the hip compared to those with low physical load in both activities. Potential confounding factors, such as age, body mass index, and smoking, were considered. Long-term exposure to sports among men seems to be a risk factor for developing severe osteoarthrosis of the hip; this is increased when combined with heavy load from occupation. PMID- 8465913 TI - Lower extremity equipment-related injuries in alpine recreational skiers. AB - Lower extremity equipment-related injuries are the most significant injury group in alpine skiing. The lower extremity equipment-related injuries occurring at four Norwegian ski resorts were studied during the winter of 1985 to 1986. A total of 132 skiers with injuries were included (40% of all injured skiers) and compared with a randomly selected control population of 316 uninjured skiers. The most common lower extremity equipment-related injuries were knee sprains (56%) and lower leg fractures (14%), usually caused by no or late binding release. Significantly more lower extremity equipment-related injuries (33%) than other skiing injuries (19%) needed hospital admittance. Children below 10 years had a risk of lower leg fractures nine times that of skiers beyond 20 years. Beginners were six times more at risk for a lower extremity equipment-related injury than skiers of higher skiing abilities. The following factors were also associated with a significantly increased risk for a lower extremity equipment-related injury: less than three skiing seasons, no skiing instruction, and no self testing of the bindings. PMID- 8465914 TI - Deterioration of patellofemoral articular surfaces after anterior cruciate ligament reconstruction. AB - One hundred eighty-seven patients who had undergone intraarticular anterior cruciate ligament reconstruction using either a fresh-frozen allogeneic tendon or central third autogenous pateller tendon 3 to 89 months previously were arthroscopically evaluated. The focus was on secondary changes of the patellofemoral joint at the time of second-look arthroscopy. Overall, 93 knees deteriorated, 74 knees remained unchanged, and 14 improved. The deteriorative changes were predominantly located around the central ridge of the patellae, although all but two knees remained free from anterior knee pain. Statistical multivariate analysis showed surgical approach by conventional medial parapatellar incision and use of the central one-third of the autogenous patellar tendon graft as possible risk factors for the deterioration, although chi-square analysis failed to demonstrate statistical significance for the latter. PMID- 8465915 TI - An in vitro analysis of patellofemoral contact areas and pressures following procurement of the central one-third patellar tendon. AB - Patients have complained of pain after the use of the central one-third patellar tendon for reconstruction of the anterior cruciate ligament-deficient knee. This study investigated the effect on patellofemoral contact areas and pressures of harvesting the central 10 mm of the patellar tendon in five cadaveric knees. Isometric quadriceps forces were applied to produce approximately 30% of reported maximum voluntary extension moments at the knee. Using Fuji pressure-sensitive film, measurements were recorded for three states: the normal knee, after the graft removal, and after the tendon was closed. Contact areas and pressures were measured at 20 degrees, 30 degrees, 60 degrees, and 80 degrees of knee flexion in each specimen. Tests of the reproducibility of our methods were performed. Average patellofemoral contact areas for three states ranged from 1.6 cm2 at 20 degrees of knee flexion to 3.0 cm2 at 60 degrees. The average patellofemoral contact pressures ranged from 1.9 MPa at 20 degrees of knee flexion to 3.0 MPa at 30 degrees. At each flexion angle there were no significant differences in average patellar contact area or pressure for the three states (P < 0.05). These results suggest that neither harvesting the central 10 mm of the patellar tendon, nor closing the gap, significantly alters patellofemoral contact area or pressure. PMID- 8465916 TI - "Bone bruises" on magnetic resonance imaging evaluation of anterior cruciate ligament injuries. AB - Magnetic resonance imaging of the knees of 98 consecutive patients with clinically diagnosed anterior cruciate ligament injuries revealed 47 patients (48%) with focal signal abnormalities consistent with the diagnosis of a "bone bruise." Seventy-one percent of the magnetic resonance images taken within 6 weeks of injury demonstrated a bone bruise, whereas no scans done longer than 6 weeks after injury showed a bruise (P < 0.0001). Also significant was the tendency for lesions to be located in the lateral compartment (P < 0.0001). In the sagittal plane, lesions were most likely to be in the middle third of the lateral femoral condyle and the posterior third of the lateral tibial plateau (P < 0.0001). In 31 patients evaluated arthroscopically, there was no correlation between the presence or location of a bone bruise and articular alterations or meniscal tears observed at surgery. PMID- 8465917 TI - The influence of an ankle orthosis on the talar and calcaneal motions in chronic lateral instability of the ankle. A stereophotogrammetric analysis. AB - The mechanical support provided by a semirigid ankle orthosis was tested in 14 ankles with symptoms of chronic lateral instability by use of stereophotogrammetric analysis. Talar and calcaneal rotations were measured with and without the Strong ankle orthosis during manual adduction test and adduction test with a predetermined torque (5 N-m). Significant reduction of talar and calcaneal plantar flexion, internal rotation, and varus angulation was noted when the orthosis was applied. The results of this study suggest that the semirigid orthosis may provide enough external support to prevent ankle sprains and to protect ligament reconstructions. PMID- 8465918 TI - Hamstrings--an anterior cruciate ligament protagonist. An in vitro study. AB - A cadaveric model that incorporated quadriceps and hamstrings muscle loads was developed to simulate the squat exercise. The addition of hamstrings load affected knee kinematics in two ways. First, anterior tibial translation during flexion ("femoral roll-back") was significantly reduced (P = 0.003) and second, internal tibial rotation during flexion was reduced (P = 0.008). However, quadriceps force was unaffected by the addition of hamstrings load. Thus, it seems likely that hamstrings muscle activity that has been observed in vivo during a squat probably functions synergistically with the anterior cruciate ligament to provide anterior knee stability. After the ACL was sectioned, anterior tibial translation was significantly increased during the squat (P = 0.04). The anterior cruciate ligament was then reconstructed using a graft instrumented with a load cell. During passive motion, maximal graft tension was at full extension. During simulated squat exercise, the addition of hamstrings caused a significant decrease in graft load (P = 0.006). During the squat, maximal graft tension was at full extension, and was equal to the graft tension at full passive extension. Thus, the squat exercise may be useful in the early stages of anterior cruciate ligament rehabilitation. PMID- 8465919 TI - Shoulder pain in wheelchair athletes. The role of muscle imbalance. AB - Shoulder rotator cuff impingement syndrome is a common and disabling problem for the wheelchair athlete. In this study we investigated the role of shoulder strength imbalance as a factor for the development of this syndrome. Nineteen paraplegic male athletes underwent clinical and isokinetic examination of both shoulders with peak torque values measured in abduction, adduction, and internal and external rotation. Twenty athletic, able-bodied men without shoulder problems were tested as controls. Ten (26%) of the paraplegic athletes had rotator cuff impingement syndrome. The results of the isokinetic testing demonstrated that 1) the paraplegics' shoulders were stronger than the controls in all directions (P < 0.05); 2) the strength ratio of abduction: adduction was higher for paraplegic athletes (P < 0.05); 3) paraplegics' shoulders with rotator cuff impingement syndrome were weaker in adduction and external and internal rotation than the paraplegic athletes without impingement syndrome (P < 0.05); and 4) paraplegics' shoulders with rotator cuff impingement syndrome had higher abduction:adduction and abduction:internal rotation strength ratios than the shoulders of paraplegics without impingement syndrome (P < 0.05). We concluded that shoulder muscle imbalance, with comparative weakness of the humeral head depressors (rotators and adductors), may be a factor in the development and perpetuation of rotator cuff impingement syndrome in wheelchair athletes. PMID- 8465920 TI - The effect of early versus late return to vigorous activities on the outcome of anterior cruciate ligament reconstruction. AB - The effect of early (mean, 5 months) versus late (mean, 9 months) return to vigorous cutting activity on the long-term outcome of anterior cruciate ligament reconstruction was evaluated retrospectively. Sixty-four reconstructions, using a distally attached medial one-third patellar tendon, were reviewed on an average of 46 months postoperatively. After surgery, the timing of return to vigorous activity was based on biologic fixation of the graft, a negative Lachman test, absence of effusion, and the patient's desire to return to previous activity. The 64 patients were retrospectively separated into two groups. The early group consisted of 31 patients who returned to activity 2 to 6 months after reconstruction, and the late group consisted of 33 patients who returned to activity 7 to 14 months after reconstruction. By clinical examination, KT-1000 arthrometer measurements, subjective evaluation, and Cybex testing, there were no differences between the early and late return groups except for reestablishment of final range of motion. At an average followup of 46 months, this study indicates that an early return to vigorous physical cutting activities after ACL reconstruction does not predispose patients to reinjury or a less satisfactory longterm result. PMID- 8465921 TI - Arthroscopically assisted anterior cruciate ligament reconstruction with the pes anserine tendons. Comparison of results in acute and chronic ligament deficiency. AB - Fifty anterior cruciate ligament-deficient knees treated consecutively with arthroscopically assisted reconstruction using a pes anserine tendon autograft were retrospectively studied. The mean followup was 36.7 months (range, 26 to 58). All patients had reconstruction with a double-stranded graft. The mean injury to surgery interval was 9.6 days in 22 patients (acute group) and 22.5 months in 28 patients (chronic group). Objective outcome, which was noted to be more optimal in the acute group, was better than subjective outcome in either group. Examination revealed 95% of patients treated acutely and 82% of those treated later to have 1+ or less Lachman test result (P < 0.036) and 96% of the acute group and 82% of the chronic group to have an absent pivot shift (P < 0.036). Eighty-eight percent of acutely treated patients had a KT-1000 result of < or = 3 mm, as compared to 61% of chronically treated patients (P < 0.001). Loss of range of motion was significantly greater in the acute group (P < 0.018). Using a strict overall rating system, patients reconstructed earlier were noted to have a better outcome compared to those after delayed reconstruction (P < 0.021). Cumulative meniscal injury appears to be the most significant contributing factor. PMID- 8465922 TI - The role of the lateral extraarticular restraints in the anterior cruciate ligament-deficient knee. AB - We measured the increases in tibiofemoral motion when lateral structures were sectioned in anterior cruciate ligament-deficient knees of 20 unembalmed cadaveric whole lower limbs. Motion was measured with a six degrees-of-freedom electrogoniometer. The lateral structures investigated were the iliotibial band and mid-lateral capsule, lateral collateral ligament, and popliteus tendon and the posterolateral capsule. Cutting the anterolateral structures increased anterior translation and internal rotation, particularly in flexion. Increases in motions were highly variable, reflecting the variation in function in the lateral collateral ligament and posterolateral structures. Cutting the lateral collateral ligament produced small changes in anterior translation and external rotation and larger increases in adduction. Cutting the posterolateral structures produced small increases in external rotation. Large increases in external rotation were found only if the lateral collateral ligament was also sectioned. The posterolateral structures act in concert with the lateral collateral ligament in restraining internal and external rotation. External rotation was affected at all flexion angles; internal rotation was affected mainly in extension. Our results can be used in the diagnosis of complex knee ligament injuries. Findings of increased anterior translation in both flexion and extension and increased internal rotation at 90 degrees of flexion are consistent with combined injury to the anterior cruciate ligament and the anterolateral structures. The anterior cruciate ligament-deficient knee with significant posterolateral compromise (posterolateral structures/lateral collateral ligament) would exhibit larger anterior translation in extension than in flexion, increased adduction, and increased external rotation in both flexion and extension. PMID- 8465923 TI - The effect of rehabilitation and return to activity on anterior-posterior knee displacements after anterior cruciate ligament reconstruction. AB - Anterior-posterior knee displacements were measured sequentially with the KT-1000 arthrometer on 84 patients after anterior cruciate ligament reconstruction for chronic deficiency. We determined the correlations between the initial onset of abnormal displacements (greater than 2.5 mm between limbs) and time from surgery or the phase of rehabilitation. Group 1 (N = 52) had a bone-patellar tendon-bone allograft and Group 2 (N = 32), an iliotibial band extraarticular procedure in addition to the allograft. The mean followup was 37 months (range, 23 to 65). At followup in Group 1, 24 patients (46%) had less than 3 mm of displacement between limbs, 22 (42%) had 3 to 5.5 mm, and 6 (12%) had greater than 5.5 mm. In Group 2, 23 patients (72%) had less than 3 mm of displacement, 8 (25%) had 3 to 5.5 mm, and 1 (3%) had greater than 5.5 mm. The difference between the groups was significant (P < 0.05). The advanced rehabilitation program of immediate knee motion and early weightbearing, did not result in an increased incidence of abnormal displacements in the early phases. The abnormal displacements typically occurred during the latter two rehabilitation phases (intensive strength training or return to sports). Further, one-third of the abnormal displacement occurred more than 2 years postoperatively. PMID- 8465924 TI - Women's gymnastics injuries. A 5-year study. AB - A 5-year prospective study on the time course of women's gymnastics injuries was conducted on a successful NCAA Division I team. Gymnasts recorded injuries on a computer terminal or via computer dot sheets immediately before each training session, including the injured body part, the event or activity, and the date of the injury. The definition of injury was "any damaged body part that would interfere with training." Athletes recorded injuries on the 1st day of onset and subsequently until the injury was healed. The initial onset of injury was considered a new injury. Subsequent records of the injury were considered continuing injury. Thirty-seven athletes participated through five collegiate seasons. They accounted for 5602 total training exposures with an average of 151.4 exposures per athlete. The analyses showed that gymnasts trained with an injury approximately 71% of the exposures, and a new injury could be expected from a gymnast during approximately 9% of the exposures. The largest number of injuries were of the repetitive stress syndrome type. The time series information showed that total injuries tended to increase until the middle of the competitive season, while new injuries showed prominent increases during specific training periods and during competition preparation and performance. PMID- 8465925 TI - Arthroscopic and histologic analysis of human patellar tendon autografts used for anterior cruciate ligament reconstruction. AB - To evaluate the fate of patellar tendon autografts in humans, the knees of 23 patients who had undergone anterior cruciate ligament reconstruction were examined 3 weeks to 6.5 years postoperatively. Arthroscopy and biopsy were performed on all patients. The patellar tendon autografts progressed through four stages of ligamentization after reconstruction. The first stage of repopulation occurred during the first 2 months and was evidenced by a viable 3-week specimen with an increasing fibroblast number and active nuclear morphology. Over the next 10 months, the graft went through a stage of rapid remodeling in which the fibroblast count increased markedly, the active nuclear morphology and neovascularity remained increased, and more areas of degeneration were present as the percentage of mature collagen decreased. The third stage or "maturation" stage occurred over the next 2 years and was characterized by a slow decline in the nuclei and the maturation of the collagen matrix. By 3 years the grafts were ligamentous by all histologic criteria examined. The authors conclude that human autogenous patellar tendon grafts are viable as early as 3 weeks postoperatively and may not go through a necrotic stage. They then progress through a prolonged process of ligamentization that takes as long as 3 years to complete. PMID- 8465926 TI - Knee flexor and extensor strength during concentric and eccentric muscle actions after anterior cruciate ligament reconstruction using the semitendinosus tendon and ligament augmentation device. AB - The purposes of this study were to compare operated and nonoperated knees after anterior cruciate ligament reconstruction using the semitendinosus tendon and a polypropylene ligament augmentation device, and to determine the interrelationships among strength, knee stability, and current activity levels. Isokinetic tests for knee flexion (prone position) and extension (sitting position) strength during concentric-eccentric muscle action cycles were completed at 60 and 180 deg/sec angular velocities, and passive anterior displacement were determined for 15 male and 15 female patients (mean age, 27 +/- 8 years; mean time since surgery, 21 +/- 3 months). With the exception of eccentric muscle actions during knee extension, peak torque and work done were significantly greater on the nonoperated leg (P < 0.05). Passive anterior displacement was significantly greater in the operated than the nonoperated knee (P < 0.01). Strength measurements tended to be modestly related to current activity level (R > 0.40 in 24 of 32 correlations; P < 0.05), whereas anterior displacement was not related to current activity level (R = -0.19, operated knee; R = -0.09, nonoperated knee; P > 0.05). Greater emphasis should be directed toward strengthening the knee flexors and knee extensors after this surgery. Although joint-specific tests (completed actively via isokinetic dynameter) are more related to activity levels than are knee laxity tests (completed passively via knee arthrometer), neither test should be relied on as the only predictor of activity level in this patient population. PMID- 8465927 TI - Roofplasty requirements in vitro for different tibial hole placements in anterior cruciate ligament reconstruction. AB - In this study we sought both to quantify the forces that result in anterior cruciate ligament graft impingement and the amount of roofplasty necessary to prevent it. The perpendicular force of the intercondylar roof against an anterior cruciate ligament graft was measured in seven fresh-frozen cadaveric knees. Two tibial hole placements were evaluated: an anterior/eccentric hole (26.6% +/- 3.1% of the sagittal depth) and a customized hole aligned 4 to 5 mm posterior and parallel to the slope of the intercondylar roof in the extended knee (42.0% +/- 2.6% of the sagittal depth). A transducer that measured the contact force with the graft was implanted in the roof. An extensive roofplasty was performed so that the sensor would bear all of the roof force. Graft tension was also measured. Extension moments were applied to 20 N-m with a six degree of freedom load application system. Load cycles were repeated with the roof force sensor backed out in 0.8 mm increments. The sensor backout represented a corresponding amount of bone removal in a roofplasty. The flexion angle at roof-graft contact was consistently greater using the anterior tibial hole than the customized one. This held true for all increments of sensor backout. With the anterior hole, the roof sensor (no backout) contacted the graft at 12.8 degrees +/- 6.7 degrees of flexion, whereas the customized hole resulted in contact at 4.1 degrees +/- 4.2 degrees (P = 0.020).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465928 TI - Relationship between changes in length and force in in vitro reconstructed anterior cruciate ligament. AB - The effect of tibial and femoral attachment site on the length change and force of an anterior cruciate ligament graft during unloaded flexion in eight cadaver specimens was examined. Two tibial sites (anteromedial and central portion of the anterior cruciate ligament attachment) and three femoral sites (anterior and central portions of the anterior cruciate ligament attachment, and over-the-top) were evaluated. Graft length changes between all combinations of attachment sites were measured from full extension to 150 degrees of passive flexion at 15 degrees intervals using the displacement of a 2-mm inextensible cord. The anterior cruciate ligament was then reconstructed using a Kennedy Ligament Augmentation Device, and graft forces at the same angles of passive flexion were measured with a buckle transducer. Graft length change and force were more affected by the femoral attachment site than the tibial site. There was a close correlation between length change and force measurements in flexion, but not near extension. The pattern of force and length change versus flexion angle for a given combination of attachment sites sometimes varied over the knees tested. Our results suggest that intraoperative isometry measurements are worthwhile for indicating an overloaded graft in flexion; however, length changes near extension may not adequately reflect graft force, creating the possibility that a graft may be more highly loaded than realized. PMID- 8465929 TI - Effects of postoperative immobilization on the reconstructed anterior cruciate ligament. An experimental study in rabbits. AB - To investigate the effects of postoperative immobilization and limited motion on reconstructed anterior cruciate ligaments, 28 rabbits received an anterior cruciate ligament reconstruction using autogenous Achilles tendon and were then divided into three groups: fully immobilized, 4 weeks immobilized, and limited motion. Two rabbits from each group were evaluated macroscopically, histologically and microangiographically at 4-week intervals until 12 weeks postoperatively. An additional six rabbits in the 4 weeks immobilized and limited motion groups were studied biomechanically at 12 weeks postoperatively. Macroscopically, both immobilized groups showed more proliferation of the infrapatellar fat pad, which was adherent to the reconstructed anterior cruciate ligament. Histology revealed more rapid regeneration of reconstructed anterior cruciate ligaments in the limited motion group, with no findings of necrosis in the mid-substance. Microangiography indicated faster normalization of vascularity in the limited motion group. The biomechanical study showed no significant difference in laxity between the 4 weeks immobilized and limited motion groups. The graft stiffness and maximum load to failure were greater for the limited motion group, although the increase was not statistically significant. The histologic and microangiographic results from the limited number of animals in this study support limited postoperative motion in the anterior cruciate ligament reconstructed knee. However, there were no differences in terms of the biomechanical parameters at 12 weeks postoperatively between the immobilized and limited motion treatment modes. PMID- 8465930 TI - Women's intercollegiate gymnastics. Injury patterns and "permanent" medical disability. AB - A prospective study was established to record the patterns of injury incurred by all members of women's college gymnastics team. Twenty-six women were followed over a 4-year period (53 gymnast seasons) from 1983 to 1987. To identify which injuries resulted in persisting impairment, these same athletes were contacted again 3 years later. The 26 athletes sustained 106 injuries. Sixty (57%) of these were of acute onset and were related to an identifiable gymnastics event. The remaining 46 (43%) were of gradual onset or overuse injuries. For the follow-up phase, 22 of the 26 women were contacted from 10 to 70 months (38.5 average) after completion of their gymnastics careers. Forty-five percent of the injuries recorded in their competitive years still bothered them at the time of followup, especially low back, ankle, great toe, shoulder, and knee injuries. Athletic and recreational activity exacerbated the complaints. Twenty-nine percent felt that their sports activity level was now limited. Forty-six percent felt that their injury was at less than full recovery, yet most felt that they were capable of strenuous physical activity and continued to be active despite complaints such as pain and stiffness. PMID- 8465931 TI - Simultaneous dorsal dislocation of both interphalangeal joints in a finger. AB - This paper has described three cases of simultaneous dorsal dislocation of both interphalangeal joints of a finger. Although two of three patients had minimal limitation of the active range of motion of the PIP and DIP joint, none had complaints of functional disability in their finger. PMID- 8465933 TI - Scaphoid waist fracture in a weight lifter. A case report. PMID- 8465932 TI - Posterior tibial nerve impingement from a tibial spine fixation screw. A case report. PMID- 8465934 TI - [Ambulatory myringoplasty]. AB - Description of a technique for ambulant Myringoplasty applicable to repair tympanic perforations no greater than a drum quadrant, by means of lyophilized dura mater and perichondrium. The results in 61 cases, two years after surgery, were gratifying both otoscopically and audiologically, and accordingly the AA, vindicate this alternative option for endaural myringoplasty. PMID- 8465935 TI - [Maxillo-facial site of localized and widespread forms of ossifying myositis. Literature review and discussion of two clinical cases]. AB - This paper present 2 different cases of extra-articular ankylosis of the temporo mandibular joint by a maxillo-facial presentation of localized and generalized ossifying myositis. A review of the literature about this subject allow the AA, to describe the clinical, diagnostical and therapeutic features of this unusual pathology. PMID- 8465936 TI - [Echography of the thyroid gland]. AB - Report on the value of ultrasonic studies in thyroid "cold nodules" prior to surgery. In 196 cases was done this complementary examination which was correlated afterwards with the anatomopathological findings, in all of them. The pathologist control is the most valuable aspect of the work done, in the A's opinion. PMID- 8465937 TI - [Tuberculoma as expansive process of the cerebellopontine angle. Case report and bibliographical survey]. AB - We present a case of intracranial Tuberculoma of the cerebellopontine angle and discuss the problems to set up the preoperative etiological diagnosis. Finally we make a review of the literature of the subject. PMID- 8465938 TI - [Idiopathic associated paralysis of the Xth and XIIth cranial nerves]. AB - We are putting forward a case of associated laryngeal paralysis placed among the paralyses of the lateral pharyngeal area. Due to the association of the Xth and XIIth cranial nerves we could consider it within the labelled as Tapia's syndrome. Nevertheless, the presumable viral etiology of the case makes such classification entitled to discussion, because only are accepted as etiopathogenetic noxes both the traumatisms and tumours. PMID- 8465939 TI - [Necrotic sialometaplasia of the hard palate]. AB - Necrotizing Sialometaplasia is an intrabucal bening pathological change, clinically presented as an ulceration of the hard palate. Either clinically or histologically its resemblance with an squamous carcinoma offers heavy problems of differential diagnosis. The process heals spontaneously in different periods of time. The AA. present 2 cases diagnosed at their Department. PMID- 8465940 TI - [The phylogenetic imprint on the embryonic development of the inner ear]. AB - The AA. present a review of the embryologic development of the internal ear linked with evolutive phylogenic events, which will determine the morphogenesis of this organ, of ancestral origin. The significance of those phenomena in order to bring about several physiological attributes as the possibility of vestibular hearing and even to set off pathologic conditions like the otosclerosis are considered. PMID- 8465941 TI - Enzymatic synthesis of 6R-[U-14C]tetrahydrobiopterin from [U-14C]GTP. AB - An enzymatic method for preparing 6R-[U-14C]-tetrahydrobiopterin from [U-14C]GTP is presented. This method utilizes purified preparations of three biosynthetic enzymes for 6R-tetrahydrobiopterin, i.e., Escherichia coli GTP cyclohydrolase I, rat 6-pyruvoyl-tetrahydropterin synthase, and rat sepiapterin reductase. Based on the catalytic properties of these enzymes, the reaction conditions were optimized to complete the entire conversion reaction from GTP to 6R-tetrahydrobiopterin in a single reaction solution without the need to isolate unstable intermediates after each enzymatic reaction. The reaction conditions thereby established yielded [U-14C]biopterin in an amount equivalent to 75%, on a molar basis, of the initial amount of [U-14C]GTP. The product was subsequently isolated by high performance liquid chromatography. The method produced labeled 6R tetrahydrobiopterin with a specific activity of 450 Ci/mol and an overall yield of more than 60%. PMID- 8465942 TI - N-isopropyliodoacetamide in the reduction and alkylation of proteins: use in microsequence analysis. AB - A new reagent, N-isopropyliodoacetamide (NIPIA), for alkylation of sulfhydryl groups on proteins for microdigestion and microsequencing is described. The utility of this reagent in both of these procedures has been demonstrated. NIPIA was shown to be especially useful in microsequence analysis, where it yields high sensitivity in detection of Cys residues. This is because the phenylthiohydantoin (PTH) derivative of NIPIA-alkylated cysteine [PTH-Cys(NIPCAM)] appears as a sharp peak in a standard reverse-phase HPLC analysis of PTH amino acids, and elutes between PTH-Tyr and PTH-Pro where no other peaks are present. Thus the use of NIPIA circumvents various problems associated with HPLC analysis of PTH-Cys when other commonly used agents are employed for sulfhydryl alkylation, such as coeluting peaks or low signal levels. Procedures for the synthesis of NIPIA and other analogs, as well as PTH-Cys(NIPCAM), are also presented, and HPLC retention times for their corresponding PTH-Cys derivatives are compared. PMID- 8465943 TI - Reduction of ricin toxicity without impairing the saccharide-binding properties by chemical modification of the carboxyl groups. AB - The usefulness of ricin as a research tool is handicapped by its extremely biohazardous nature. In this work, ricin toxicity has been reduced by chemical modification of carboxyl groups using 1-ethyl-3(3-dimethylaminopropyl) carbodiimide and [14C]glycine methyl ester. The reaction was carried out in 8 M urea and in the presence of 0.1 M lactose to protect the groups involved in saccharide binding. Together with carboxyl groups, tyrosine residues were also modified. The maximum modification achieved was 13 carboxyl groups and 7 tyrosines per molecule (about 30% of total carboxyls and tyrosines). The modification did not alter substantially the strength and specificity of the carbohydrate-binding ability of the lectin, as observed by hemagglutination tests and by inhibition assays with different carbohydrate structures. However, the LD50 decreased 90-fold when the highest modification was achieved. Therefore, the modified lectin can be used more safely in the study of galactose-containing carbohydrates. PMID- 8465944 TI - Quantitation of hydroperoxy-eicosatetraenoic acids and hydroxy-eicosatetraenoic acids as indicators of lipid peroxidation using gas chromatography-mass spectrometry. AB - Peroxidation of cellular membrane lipids has been implicated in a wide variety of acute and chronic pathologies. We have developed a method for quantifying lipid peroxidation products using gas chromatography-mass spectrometry (GC-MS) in order to help elucidate the role of lipid peroxidation in such disorders. The method involves analysis of the methyl ester, trimethylsilyl ether derivatives of various hydroxyeicosatetraenoic acids (HETEs). 16-Hydroxy-9,12,14 heneicosatrienoic acid was synthesized for use as an internal standard. The assay involves the following steps: The internal standard is added to the sample and cellular lipids are extracted and trans-esterified. Next, any hydroperoxides are reduced with triphenylphosphine and the samples are subjected to two steps of solid phase extraction. The samples are then hydrogenated and the trimethylsilyl ether derivative of the hydroxyls formed. The derivatized HETEs are analyzed by electron impact GC-MS. 12-HETE, 11-HETE, 9-HETE, and 8-HETE are assayed by monitoring ions at m/z 301, 287, 259, and 271, respectively. Standard curves were constructed for each HETE and were linear over the range 1 to 250 ng; correlation coefficients were typically greater than 0.99. The assay has been applied to the study of autoxidation of lipids in both in vitro and in vivo systems. PMID- 8465945 TI - Rapid and accurate microfractionation of the contents of small centrifuge tubes: application in the measurement of molecular weight of proteins via sedimentation equilibrium. AB - The contents of small centrifuge tubes containing solutions of radiolabeled proteins that had been centrifuged to sedimentation equilibrium were fractionated using a new device based upon the mechanical design of Attri and Minton (Anal. Biochem. 152, 319-328, 1986). Individual fractions, corresponding to laminae of 0.15 mm column height within the tube, were collected using one of two methods: (a) automatic mixing with scintillation fluid and delivery to vials mounted in a fraction collector, or (b) collection of undiluted fractions on scintillation vial caps impregnated with solid scintillator. Gradients of protein concentration were obtained via scintillation counting of sequential fractions. Molecular weights of proteins ranging from 4 x 10(4) to 3.5 x 10(5) were calculated by fitting the theoretical expression for sedimentation equilibrium of an ideal homogeneous solute to the experimental gradients. The values so obtained agree well with values obtained by optical scanning of the unfractionated centrifuge tube, and with values obtained from the literature. PMID- 8465946 TI - A method to detect polysialic acid in polymers of 10 or more sialyl residues synthesized in vivo and in vitro. AB - An immunoaffinity column has been used to detect polysialic acid containing 10 or more sialyl residues. Antibodies specific for colominic acid were purified from horse serum by immobilized colominic acid and were bound to CH-Sepharose-4B. The immunoaffinity column was used to assay the activity of CMP-NeuNAc: poly alpha 2- >8-sialosylsialyltransferase by detecting the products which were synthesized in vitro by an extract from rat brain and CMP-[14C]NeuNAc. In addition, polysialic acid was demonstrated in a fraction of glycoproteins from human neuroblastoma cells, labeled metabolically with [3H]GlcN. The column was further characterized by binding of 3H-colominic acid and by treatment of the bound polymers with endoneuraminidase, specific for the degradation of polysialic acid. The method can be used for rapid detection of polysialic acid synthesized in vivo and in vitro. PMID- 8465948 TI - Silver-enhanced copper staining of protein blots. AB - Copper staining of protein blots has previously been shown to detect proteins rapidly, quantitatively, and sensitively. The sensitivity of this assay can now be enhanced nearly 10-fold with an additional step of silver staining. The silver enhanced assay retains many of the virtues of copper staining, including a quantitative optical response with the amount of adsorbed protein, low variation between proteins, and reversibility. In addition, both copper staining and silver enhanced copper staining do not detect nucleic acid, thus allowing for selective measurement of nucleic acid binding proteins or protein contamination in nucleic acid preparations. Silver-enhancement requires only a 5-min incubation with a single reagent. Since copper staining is performed first, it can be used to determine if the greater sensitivity provided by silver enhancement is desirable. For quantitation, an inexpensive reflectance scanning densitometer utilizing optical scanners and NIH Image is described. PMID- 8465947 TI - Synthesis of [35S]thiophosphoryl adenylic acid, utilizing a general procedure for [35S]thiophosphoryl chloride production. AB - Elemental [35S]sulfur was shown to equilibrate with the sulfur of thiophosphoryl chloride when these materials are heated together. This isotopic exchange reaction is the basis of a convenient, microscale synthesis of high specific activity [35S]PSCl3. [35S]Thiophosphoryl chloride is otherwise not commercially available except through custom synthesis. The labeled thiophosphoryl chloride was used in a novel procedure for the preparation of [35S]adenosine 5' phosphorothioate. This isotopic exchange method should find wide application in the synthesis of many radiolabeled thiophosphoryl esters which utilize PSCl3 as the source of the thiophosphoryl group. PMID- 8465949 TI - A thin-layer gas-solution microcalorimeter for the determination of heat binding curves. AB - A thin-layer gas-solution microcalorimeter has been developed to study the binding reactions of gaseous ligands with ligand binding macromolecules in solution. Gas partial pressures are accurately changed logarithmically by means of a precision dilution valve allowing for the stepwise determination of reaction heats. Heat binding curves are constructed in which the enthalpy per mole of reaction site is plotted versus the logarithm of the ligand activity. MicroJoule sensitivity is achieved through closed loop proportion computer control and precisely twinned highly isolated sample and reference geometry. The sample, typically 50 microliters and 1 to 4 mM heme protein, is placed on a filter paper membrane which acts as a matrix of support. This orientation allows for the rapid equilibrium of reacting ligand in approximately 10 min while not significantly altering the ligand activity. The system is controlled by computer measuring the heat of reaction as the partial pressure is changed automatically, typically by flushing the system with reacting ligand then reducing its partial pressure logarithmically with a nonreacting gas such as nitrogen. Binding curves can be constructed with as little as 20 nmol of oxygen binding sites. PMID- 8465950 TI - An assay to detect glycoproteins that contain mannose 6-phosphate. AB - We have developed a broadly applicable solid phase assay for quantitative and qualitative analysis of phosphorylated lysosomal enzymes and other glycoproteins that contain mannose 6-phosphate (Man6-P) residues. Samples are immobilized on membranes and proteins that contain Man6-P are detected using an iodinated, soluble form of the cation-independent Man6-P receptor. The assay is highly specific, sensitive, and linear over 3 orders of magnitude. The technique has two general applications. First, it can be used in a dot blot format to analyze large numbers of samples for total levels of Man6-P glycoproteins. Second, it can be used in a western blot format to identify Man6-P glycoproteins that have been fractionated by polyacrylamide gel electrophoresis. Specific applications of this novel assay include structural characterization of glycoproteins, diagnosis of mucolipidosis II and III, and screening of pharmaceuticals for lysosomotropic activity. Other potential applications are discussed. PMID- 8465951 TI - A method for identifying the carboxy terminal amino acid of a protein. AB - A highly sensitive new method for identifying the carboxy terminus of a protein was developed. The carboxyl terminal amino acid was racemized by reaction with acetic anhydride. The resulting modified protein was subjected to acid hydrolysis. The hydrolysate was derivatized with (+)-1-(9-fluorenyl)ethyl chloroformate to give fluorescent amino acid diastereomers. The amino acid diastereomers were separated on a reversed-phase column. Only carboxyl terminal amino acids give a D-amino acid. Application of this method was described for the isolation and identification of carboxyl terminal peptides from an enzymatic digest of a protein. PMID- 8465952 TI - Combined alcian blue and silver staining of subnanogram quantities of proteoglycans and glycosaminoglycans in sodium dodecyl sulfate-polyacrylamide gels. AB - Proteoglycans stain weakly in polyacrylamide gels by traditional protein stains such as coomassie brilliant blue or silver. In the present work preparations of large aggregating proteoglycan from human articular cartilage were used to evaluate a convenient staining method based on successive staining with alcian blue and neutral silver. The method is developed for sodium dodecyl sulfate polyacrylamide gel electrophoresis; with ultrathin minigels in a semiautomated electrophoresis system, takes 1 1/2 h, and uses stable reagents. Preparations, electrophoresis, and staining of up to 24 samples can be completed within 2 1/2 h. The method has a detection limit of 0.04-1 ng proteoglycan and less than 0.5 ng of glycosaminoglycan. In addition the method can be adjusted for selective staining of proteoglycans and glycosaminoglycans. PMID- 8465953 TI - Methods for electrophoretic karyotyping of filamentous fungi in the genus Trichoderma. AB - Methods for electrophoretic karyotyping of filamentous fungi in the genus Trichoderma were developed. These techniques permitted the separation and visualization of intact chromosomes from viable protoplasts. Three strains were analyzed: Trichoderma harzianum strains T12 his-2 and T95 lys-1, and a prototrophic strain (1295-22) produced by protoplast fusion of T12 his-2 with T95 lys-1. Four chromosome bands ranging in size from 2.2 Mb (megabase pairs) to 5.4 Mb were visualized with strain T95 lys-1, whereas two chromosome bands were visualized for strains T12 his-2 and 1295-22. The largest chromosome of all three strains seems to be similar in size and has been estimated to be approximately 5.4 Mb. All remaining chromosomes observed were dissimilar in size. Methods for protoplast isolation, protoplast embedding, and electrophoretic conditions useful for separation of intact chromosomes ranging in size from 50 kb (kilobase pairs) up to approximately 6.0 Mb utilizing transverse alternating field electrophoresis (TAFE) will be discussed. The techniques provided should be applicable to a variety of lower eukaryotic organisms when using the TAFE system. PMID- 8465954 TI - Enzyme complex amplification--a signal amplification method for use in enzyme immunoassays. AB - An amplification system for enzyme immunoassays, in which complexes of streptavidin, biotinylated horseradish peroxidase, antibody are used to detect biotinylated target molecules was developed. In enzyme-linked immunosorbent assay (ELISA) experiments this enzyme complex enhancement (ECA) system gave up to a better than two orders of magnitude increase in sensitivity, compared to a horseradish peroxidase-conjugated streptavidin detection system. The ECA system was shown to be applicable to direct detection of biotinylated antigens, as well as in ELISA employing biotinylated antibodies and in sandwich ELISA. The ECA system was also applicable to immunoblots, giving a sensitivity comparable to that obtained using a radiochemical detection system. PMID- 8465955 TI - A preparation of lambda phage DNA based on affinity chromatography. PMID- 8465957 TI - Rapid analysis of mammalian sperm nuclear proteins. PMID- 8465956 TI - C-terminal labeling of ribonuclease A with an extrinsic fluorescent probe by carboxypeptidase Y-catalyzed transpeptidation in the presence of urea. AB - For use in protein folding studies, ribonuclease A (RNase A), a 124-residue protein with the C-terminal sequence Phe-Asp-Ala-Ser-Val, has been labeled site specifically by a carboxypeptidase Y (CPase Y)-catalyzed transpeptidation reaction which replaces the C-terminal residue(s) of RNase A with the extrinsic fluorescent probe 3-(2-naphthyl)-L-alanine amide (Nal-NH2). It was found that this CPase Y-catalyzed transpeptidation required the presence of the chemical denaturant urea (ca. 5 M) and that, under these conditions, effective transpeptidation occurred only in the pH range of ca. 5.5 to 6.5. The two major products from this labeling reaction were purified to homogeneity by ion-exchange and reverse-phase chromatography and characterized by tryptic mapping, amino acid analysis, and mass spectrometry. The major product, obtained in the reproducible, isolated molar yield of 20%, is the derivative in which only the single C terminal residue, Val-124, is replaced directly by the probe Nal-NH2. Another isolated product, obtained in 11% yield, is the derivative in which two of the C terminal residues, Ser-123 and Val-124, are replaced by one Nal-NH2. Both of these purified derivatives are enzymatically active (85 and 18%, respectively), and both exhibit spectral properties characteristic of the extrinsic probe including an observed fluorescence lifetime which is approximately monoexponential (tau = 42 ns) when the naphthyl chromophore is excited in the region of its absorption band. PMID- 8465958 TI - Rapid isolation of full length cDNA clones by "inverse PCR:" purification of a scorpion cDNA family encoding alpha-neurotoxins. PMID- 8465959 TI - "One-buffer" protocol for primer end-labeling and subsequent dideoxy-mediated DNA sequencing. PMID- 8465960 TI - A self-consistent method for the analysis of protein secondary structure from circular dichroism. AB - A self-consistent procedure for estimating the secondary structure content from circular dichroism spectra of proteins is presented. In this method the spectrum of the protein to be analyzed is included in the basis set and an initial guess is made for the unknown structure as a first approximation. The resulting matrix equation is solved using the singular value decomposition algorithm and the initial guess is replaced by the solution. The process is repeated until self consistency is attained. The best features of the variable selection and the locally linearized methods are incorporated in this procedure. We have applied this method to examine the inconsistencies in the CD data, to compare the predictions with different ranges and resolutions of the CD data, and to compare different assignments of secondary structures from X-ray structure analyses in the context of secondary structure predictions. The results are compared using the root mean square differences and correlation coefficients. The results obtained are as good as or better than the previous analyses. For most of the proteins considered the self-consistent solutions obtained with different initial guesses were similar. We find the Kabsch and Sander protein crystal structure analysis to be most suitable for our prediction method. PMID- 8465961 TI - A rapid fluorometric method for the determination of carnitine palmitoyltransferase. AB - A rapid and sensitive fluorometric assay for the measurement of carnitine palmitoyltransferase (CPT) activity is described. In this assay the coenzyme A (CoA) liberated from palmitoyl-CoA by CPT reacts with N-(9-acridinyl)-maleimide to form a fluorescent product. By comparing the fluorescence intensities of external CoA standards, CPT activity can be determined. The coefficients of variation within-run and between-run of the method were 6.9 and 10%, respectively. The CPT activity of human muscle samples measured with this assay is comparable to those obtained with a commonly used radiochemical assay and CPT deficiency in skeletal muscle from a patient was detected by this new fluorometric assay. PMID- 8465962 TI - Two-dimensional polyacrylamide gel electrophoresis of proteins labeled with the fluorophore monobromobimane prior to first-dimensional isoelectric focusing: imaging of the fluorescent protein spot patterns using a cooled charge-coupled device. AB - A new method for visualizing 2D protein spot patterns is described whereby proteins containing sulfhydryl groups are labeled with the fluorophore monobromobimane prior to the isoelectric focusing step of 2D polyacrylamide gel electrophoresis. The method requires the addition of a single reagent and a delay of only 15 min during sample preparation. High resolution spot patterns were obtained without the need for any post-electrophoretic gel handling. The gel patterns were imaged digitally immediately post-electrophoresis while the gels were still within their glass electrophoresis cassettes. The imaging system was based on a cooled charge-coupled device. The fluorescent spot patterns of proteins from the lymphoid cell-line IM9 were similar but not identical to silver stained gel spot patterns of the same but underivatized sample. There was an overall increase (approx. 10%) in the number of spots visible on the fluorescent gels compared to those visible on the silver-stained gels. PMID- 8465963 TI - A simple method of detecting amplified DNA with immobilized probes on microtiter wells. AB - We have developed a simple hybridization method for the detection of specific DNA sequences amplified by polymerase chain reaction (PCR). This method is similar to an enzyme-linked immunosorbent assay (ELISA) format in that labeled PCR products at the 5' termini are hybridized with probes immobilized on a microtiter well and the bound PCR products are detected in a manner similar to that of an enzyme immunoassay (EIA). Two improvements have been made in immobilizing the probe to the microtiter wells, in terms of increasing both immobility and hybridization efficiency. One is that single-stranded (ss) DNA, without the complementary strand, is used. The other is that instead of a single copy, a tandem array of the probe is used for immobilization and hybridization. Using of ssDNA containing about a 60-repeat array of a relevant sequence as an immobilized probe, the sensitivity increased 10-fold over that of a single oligonucleotide unit. We also found that the hybridization conditions such as time, temperature, and solution composition could be simplified. Therefore this method is especially suited for handling of a large number of samples, for example detection of viruses, bacteria, and other pathogens, as well as mot human genetic disorders. PMID- 8465964 TI - Simultaneous determination of free tissue-type and free urokinase-type plasminogen activators in biological fluids by a solid-phase immunoassay. AB - Tissue-type and urokinase-type plasminogen activators (t-PA and u-PA) coexist in numerous biological fluids, where their fibrinolytic activities are determined by the concentration of the free, uncomplexed species. A simple, sensitive method has been developed for the simultaneous determination of free t-PA and u-PA concentrations in biological fluids using a solid-phase immunoassay. Microtiter plates were coated with polyclonal goat antibodies and incubated with PA standards or unknown samples. The absorbed PAs were then assayed by incubation with a mixture of plasminogen, poly-L-lysine, and the chromogenic substrate H-D norleucylhexahydrotyrosyllysine-p-nitroanilide. Free t-PA and free u-PA were detectable in human plasma and urine, and in conditioned media from different endothelial cell cultures. The method is sensitive, with lower limits of quantitation being 0.76 mU/ml (1.25 pg/ml) for free t-PA and 0.16 mU/ml (2.0 pg/ml) for free u-PA. There was no cross-reaction between the two PA species and the recovery in plasma was greater than 95% for both. The intra- and interassay coefficients of variation for t-PA and u-PA were 3.5-12.2 and 3.2-11.3%, and 2.4 11.8 and 1.6-10.4%, respectively. The presence of PA-inhibitor complexes and PA inhibitors in biological fluids did not interfere with the assay. Application of the assay has demonstrated that free u-PA levels are several fold higher than free t-PA levels in human plasma and in conditioned media of human vascular endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8465965 TI - Isolation of oligomannose-type glycans from bean glycoproteins. AB - We have isolated individual oligosaccharyl-asparagine derivatives from the total soluble glycoproteins from kidney beens (Phaseolus vulgaris) and from lima beans (Phaseolus limensis). The protein/glycoprotein mixture was digested exhaustively by pronase, and the glycan-containing fractions were separated from free amino acids and peptides by gel filtration. The oligosaccharyl-asparagine derivatives were finally fractionated on Dowex 50 (C. C. Huang, H.E. Meyer, and R. Montgomery, Carbohydr. Res. 13, 127-137, 1970), and the individual fractions were characterized by mass spectrometry, NMR, and ion exchange chromatography. With the procedures described, only oligomannose derivatives were obtained from the beans. In the case of kidney beans, six different derivatives were observed and characterized, Man9GlcNAc2Asn, two positional isomers of Man8GlcNAc2Asn, two positional isomers of Man7GlcNAc2Asn, and Man6GlcNAc2Asn. Under identical conditions the lima beans yielded primarily the Man9GlcNAc2Asn derivative along with a small amount of the two Man8GlcNAc2Asn derivatives. The oligomannose structures can be isolated in reasonable quantities (2-20 mg) from about 200 g of dry beans. PMID- 8465966 TI - 31P NMR examination of phosphorus metabolites in the aqueous, acidic, and organic extracts of Phaseolus vulgaris seeds. AB - 31P NMR spectroscopy was used to compare the phosphorus compound content in aqueous, acidic, and organic extracts of Phaseolus vulgaris seeds. Two chloroform methanol and three ethanol extractions were used to isolate phospholipids from dry cotyledons and the phospholipid profiles were compared. Variations in phospholipid composition and artificially high concentrations of lysophosphatidylcholine were observed in the ethanol extracts. Other phosphorus compounds were extracted using perchloric acid, trichloroacetic acid, trichloroacetic acid in ether, hydrochloric acid, boiling water, and aqueous Hepes. The Hepes extraction was introduced in order to compare the results of a gentle procedure with those involving heat and acid treatments. Low concentrations of phospho-sugars and other phosphorus metabolites were found in all these extracts. High concentrations of phytate were found in all aqueous and acidic extractions; however, 31P NMR spectra of aqueous extractions did not show the phytate resonance. The NMR silence of the phytate resonances is attributed to complexation of phytate. The 31P NMR spectra of aqueous extracts contained a broad resonance at 0.1 ppm assigned to protein-bound RNA. Various extraction procedures on the same biological material are presented, and the comparison of these methods will facilitate future analysis and interpretation of literature reports involving these methods of tissue analysis. PMID- 8465967 TI - Ultrastructure of epididymal epithelium in Equus caballus. AB - The ultrastructure of the epithelial lining of the ductuli efferents and the ductus epididymis in the horse (Equus caballus) is described. Several types of cells can be distinguished: ciliated and non-ciliated cells make up the epithelium of the ductuli efferents, whereas principal, apical and basal cells are found in the ductus epididymis. The observations are compared with those made in other species, in particular in the donkey (Equus asinus), and the possible functional roles of the different cell types are discussed. PMID- 8465968 TI - The hundred and twenty-fifth anniversary of the birth of Henryk Ferdinand Hoyer Junior (1864-1989). PMID- 8465969 TI - [Clinical anatomy of the fat body in the forearm and in the palm]. AB - In the hand the space between the deep flexor tendons and the interosseous fascia is named the midpalmar space, spatium palmare medianum. A fat body, Corpus adiposum palmare profundum, can be found there regularly. Despite the anatomical narrowness in this region, it reaches up into the carpal canal. Also in the deep forearm space there is always a fat body, Corpus adiposum profundum antebrachii, located dorsally to the deep flexor tendons, lying on the palmar fascia of the pronator quadratus muscle. Usually it is not connected to the Corpus adiposum palmare profundum. The regular occurrence of both fat bodies indicates their functional importance. It is to be supposed that they serve as a gliding layer for the deep flexor tendons. Especially the Corpus adiposum palmare profundum may provide an essential protecting function to the dorsally located deep branch of the ulnar nerve and deep palmar arch. In contrast there is a higher risk of mechanical irritation and compression of the deep branches of the ulnar nerve and artery during their more proximal course through the opponens muscle of the little finger ("opponens-canal") and the ulnar marginal septum. Characteristic features of dimensions and location of the Corpus adiposum profundum antebrachii and the Corpus adiposum palmare profundum and of the deep branches of the ulnar nerve and artery are described. The clinical relevance is discussed. PMID- 8465970 TI - Innervation of the levator scapulae, the serratus anterior, the rhomboideus and the scapular muscles in the gray kangaroo (Macropus giganteus). Comparisons are drawn to the crab-eating macaque and man. AB - The origin, course and distribution of the nerves to the levator scapulae, rhomboideus, serratus anterior, supraspinatus, infraspinatus, subscapularis, teres minor, deltoid, teres major and latissimus dorsi muscles were examined in 7 kangaroo body-halves. The levator scapulae and the serratus anterior formed a continuous muscle sheet arising from the transverse processes of the lower 5 cervical vertebrae and the upper 6 ribs. The rhomboideus arose from the occipital bone in addition to the cervical dorsal median raphe. Six segmental nerves from C3 to C8 innervated these 3 muscles. Each segmental nerve originated from the dorsal surface of the corresponding root of the cervicobrachial plexus. All these nerves innervated the levator-serratus muscle sheet and 4 segmental nerves from C3 to C6 innervated the rhomboideus. Of the remaining scapular muscles, the supraspinatus was well developed, and the teres minor was a small muscle. The nerves supplying the scapular muscles originated from the area between the upper trunk and the posterior cord of the brachial plexus. Four segmental nerves from C5 to C8 usually innervated these 7 muscles. Judging from the relationships between nerves and muscles, all of these muscles are thought to have originally belonged to the same 2 groups of the dorsal musculature extending between the trunk, the shoulder girdle, and the limb. Muscle type and modes of nerve supply to the muscles in the grey kangaroo are similar to those found in the crab-eating macaque. PMID- 8465971 TI - Interconnections of muscles in the adductor mandibulae complex of birds. AB - In addition to a variety of connections at or near the attachment of muscles, some of the adjacent bellies in the adductor mandibulae complex of birds merge with one another across the whole or most of their contiguous sides. Such continuous intermuscular transitions are found between the adductor posterior and the deep part of the adductor externus, the posterior adductor and quadratomandibularis muscle, the adductor posterior and pterygoideus muscle and between the quadratomandibularis and pseudotemporalis muscles. Since a complete breakup of the adductor premuscle mass occurs early in development and there is no indication of adult intermuscular transitions in any of the studied avian embryos, the muscles must coalesce at some stage of growth. Therefore, the intermuscular transitions of adult birds cannot be derived with any certainty from the primary connections in the adductor mandibulae of early gnathostomes. The coalescence of developmentally discrete muscles is invariably seamless and appears to be contingent not only upon the contiguity of muscles but also upon the congruent arrangement of their fibers. PMID- 8465972 TI - Age-related changes in glycosaminoglycan distribution in different anatomical sites on the surface of knee-joint articular cartilage in young rabbits. AB - In spite of the fact that the various anatomical regions of a given articular cartilage surface are subjected to different degrees of stress, the present observations strongly suggest that there exists a topographical homogeneity in the distribution of glycosaminoglycans in the same articular cartilage. In contrast to this age-related changes in the proportion of the different types of glycosaminoglycan species in articular cartilage are remarkable. Non-sulphated chondroitin could only be detected in very young articular cartilage. Dermatan sulphate, which has already been detected in young adult rabbits, was followed by the appearance of keratan sulphate in older rabbits. Chondroitin 4-6-sulphates were detected in all articular cartilages studied, the proportion of the 6 sulphated variably increasing with age. The present report suggests that the distribution of glycosaminoglycans in articular cartilage varies with species and age, and the data can further vary, depending on the methods used. It is therefore concluded that generalizations against the results reported in the literature should be considered skeptically. PMID- 8465973 TI - An ultrastructural study of mitotic chondrocytes in the proliferative zone of the rat tibial growth plate. AB - Mitotic chondrocytes containing fairly prominent cell organelles were observed in the proliferative zone of the rat tibial growth plate by electron microscopy. During the later stage of mitosis, the endoplasmic reticulum was mostly vacuolated, and the Golgi stacks were replaced by spherical and cylindrical vacuoles and small vesicles. The cytoplasmic division began at early telophase. However, the cytoplasmic cleavage furrow was so narrow that dividing chondrocytes looked as if they were partitioned by a slit. This is probably one reason for the appearance of the binuclear cells that are occasionally observed in the tibial growth plate. PMID- 8465974 TI - Changes in the coxofemoral articular cartilage in Wistar rats after systemic administration of corticoids. AB - A structural, ultrastructural and morphometric study of the coxofemoral articular cartilage of 48 Wistar rats was carried out after daily intramuscular injections of 2.5 mg prednisolone. The animals were divided into four groups, members of which were killed 15, 30, 60 and 90 days respectively after the start of the experiment. A degenerative process developed in the experimental animals, which led progressively to the death of chondrocytes in the middle zone of the articular cartilage after 90 days. Structural, ultrastructural and morphometric alterations were observed, both in cells and in the cartilage matrix. These gave rise to superficial changes in the femoral head. PMID- 8465975 TI - The coronary arteries of the Syrian hamster, Mesocricetus auratus (Waterhouse 1839). AB - Bearing in mind that the Syrian hamster provides an animal model for the study of congenital coronary artery anomalies, we decided to undertake a definition of its normal coronary artery pattern. The sample examined consisted of 1204 specimens. They were studied both histologically and by means of a corrosion-cast technique. The course of the coronary arteries in this species is intramyocardial. The right coronary artery has two principal branches: the right circumflex branch and the dorsal interventricular branch. The conal branch usually originates from the main trunk of the right coronary artery. The main branches of the left coronary artery are the obtuse marginal branch, the left circumflex branch, and usually a dorsal ventricular branch as well. The ventral interventricular branch is often absent. When it is present, it always originates from the left coronary artery and seldom reaches the apex of the heart. The interventricular septum is principally supplied by one, or rarely two, septal arteries arising from the right and/or left coronary arteries. According to the number and origin of these vessels, three septal coronary artery patterns were established; namely, the right, the left, and the right-left septal patterns. In the Syrian hamster, the left septal pattern is the most frequent (70.4%). The right septal pattern occurred in 28.1% of the specimens studied, whereas the right-left septal pattern was only found in 1.5% of them. PMID- 8465976 TI - Melano-macrophage centre-like structure in the heart of the medaka, Oryzias latipes. AB - Endocardial lining cells in the heart of certain teleosts are phagocytic against foreign materials. In the medaka Oryzias latipes, in addition to the endocardial lining cells, cells in the subendocardial spaces are also phagocytic. Most subendocardial cells contain yellowish-brown pigments and are often aggregated to form nodules resembling splenic and kidney melano-macrophage centres. Subendocardial cells are positive to PAS and Schmorl's reaction. Macrophages containing large heterogeneous inclusions together with lymphocytes, were observed with the TEM. The definitive characteristics of reticular cells, including the cell sheaths, were not observed. Because of these two characteristics they were regarded as more primitive aggregates of macrophages than the ordinary melano-macrophage centres. The possible analogy between these structures and MMCs is discussed. PMID- 8465977 TI - An update of the stereology of the myocyte of the baboon's heart: analysis of the crista terminalis, interatrial and interventricular septa, and atrioventricular bundle. AB - We used light microscopy to compare the stereology of the myocytes from the following regions of the baboon's heart: a) cardiac walls (crista terminalis, interatrial and interventricular septa) and b) cardiac conduction tissue (atrioventricular bundle). Six hearts were perfused and several pieces of tissue were taken from these regions. A staggered test lattice consisting of cycloids was superimposed on twelve random pairs of photomicrographs in order to make disectors, and on twelve other random fields for each cardiac region in order to estimate certain stereological parameters. Statistically significant differences were found when comparing the number of myocytes from the crista terminalis (highest value) with either the interatrial or interventricular septum. There is also a significant difference between the number of myocytes in the interventricular septum and the atrioventricular bundle (highest value). For the mean profile area of the myocytes, significant differences were found between the myocytes of both the crista terminalis and the interatrial septum, and those of the interventricular septum (highest value). Under the light microscope, myocytes from the two regions of the atrial wall studied were indistinguishable in size, since they constitute a single cell population. It was also impossible to distinguish them from the atrioventricular cells. The myocytes from the interventricular septum differed in both size and number from those of the right atrium, but only in number from those of the atrioventricular bundle. PMID- 8465978 TI - The hairlet follicle in the skin of the wild Norway rat (Rattus norvegicus Berkenhout, 1769). Its morphology and function. AB - The hairlet follicle of the wild Norway rat (Rattus norvegicus Berkenhout 1769) differs from the other follicles in position and in structural characteristics. As an element of the guard (tylotrich) hair follicle group the hairlet follicles are arranged at the margin of the hair disk. The hairlet follicle, which produces the finest hair fibre, is enclosed by an active unilobular sebaceous gland. The arrector pili muscle is absent, but the follicle does have a supply of lanceolate nerve endings and Ruffini endings. The axons of the lanceolate endings are enclosed sandwich-like by Schwann cells and contact the basal lamina of the outer epithelial root sheath. Ruffini endings run within the band of connective tissue fibres that girdle the follicle at the level of the sebaceous gland. The appropriate stimulus for excitation of the nerve fibres can not be achieved by bending the tiny hairlet fibre. Tissue compression, induced by bending the central guard (tylotrich) hair, which is transformed via the sebaceous gland and the slim outer epithelial root sheath, may exicite the nerves of the hairlet follicle. It can be assumed that the hairlet follicle functions as a mechanoreceptor. PMID- 8465979 TI - Neuroanatomical and immunohistochemical studies on the dorsal neurons in the spinal cord of Trigla lucerna L. and Scorpaena porcus L. (Scorpaeniformes). AB - Peculiar dorsal neurons present in the dorsal spinal cord of Trigla lucerna L. and Scorpaena porcus L. were investigated by neuroanatomical and immunohistochemical methods. These neurons were previously defined as commissural cells, but have now been identified as supramedullary neurons. The following fundamental criteria for identifying the supramedullary neurons of Teleosts are proposed: a) dorsomedial location in the spinal cord; b) large size of the soma and axon; c) immunoreactivity to gastrin/CCK-like peptides. PMID- 8465980 TI - The confronting cisternae in the hippocampal neurons of rats and Japanese monkeys. AB - The ultrastructure of the neurons in the hippocampal formation of Wistar rats and Japanese monkeys was investigated. Confronting cisternae were observed in the cytoplasm of pyramidal neurons and granule cells. The structures were composed of closely apposed parallel cisternae, presumably continuous with the cisternae of the rough endoplasmic reticulum. The cytoplasmic matrix between the confronting cisternae contained electron dense flocculent material. In the pyramidal neurons irregular confronting cisternae were also observed. Possible functions of the confronting cisternae are discussed. PMID- 8465981 TI - The development of the blood-brain barrier in the chick. Studies with evans blue and horseradish peroxidase. AB - The development of the blood-brain barrier was microscopically examined in the optic tectum of the chick. The permeability of neural vessels to Evans blue and horseradish peroxidase decreases progressively during the period of incubation. Diffusion is massive on the 6th and 10th days of incubation and is reduced on the 14th day; on the 18th-21st day of incubation the vascular walls still allow Evans blue to diffuse but prevent extravasation of horseradish peroxidase completely. In one month old chickens the nervous substrate is free of both tracers. PMID- 8465982 TI - Development of the proximal tubule of the fetal rat kidney: morphometry and ultrastructural findings. AB - The development of the kidney in fetal rats was investigated morphometrically and ultrastructurally. Both the length and volume of the proximal tubule increased with age. The total volume of functional glomeruli increased markedly from fetal day 20 onward. The ratio of total glomerular volume to total proximal tubular volume decreased with age and was less than 1 from fetal day 20 onward. The cells of the proximal tubule had numerous microvilli on their free surfaces and vacuoles in the apical region of the cytoplasm after fetal day 20. These findings indicate that the relative growth of the proximal tubule has exceeded that of the glomeruli by fetal day 20, and that increased filtration induces both the growth and the differentiation of the proximal tubule during development of the fetal rat kidney. PMID- 8465983 TI - [The cell response of rat esophagus after intraluminal irradiation with Nd-YAG laser (1064 nm) after various postoperative times: a light and electron microscopic study]. AB - The esophagi of Wistar rats were irradiated by a Nd-YAG-laser and studied by light and transmission electron microscopy immediately, 2 days and 14 days after the operation. In the immediate group the lasercentre showed a destruction of the stratified epithelium. On the contrary the cells and fibres of the underlying connective tissue were hardly affected. In the lasercentre we have found occlusion of microvascular lumina. Both the layer of smooth muscular tissue and the layer of skeletal muscular tissue showed defects in their myofilaments and altered nuclei. The damage of the skeletal muscle fibres extended up to 4 mm distant from the lasercentre. After 2 days a migrating epithelial sheet was present below the necrotic epithelium and an inflammatory reaction was found in the connective tissue. After 14 days a new regenerated epithelium and an underlying granulation tissue had caused a stenosis of the esophageal lumen. The smooth and striated muscle fibres also showed signs of regeneration. We assume a high regenerative capacity of all involved tissues. PMID- 8465984 TI - Establishment of heterogeneity among blood vessels: hormone-influenced appearance of hepatic lipase in specific subsets of the ovarian microvasculature. AB - We used biochemical and structural approaches to analyze the influence of gonadotropic hormones on the association of hepatic lipase with specific subsets of ovarian blood vessels. Western blotting was used to detect this enzyme in effluent collected from heparin-perfused ovaries of nonhormone-treated immature rats and those primed with pregnant mare's serum gonadotropin (PMSG) alone or in combination with human chorionic gonadotropin (hCG). The effects of these hormones on hepatic lipase distribution among ovarian blood vessels was assessed before and after hCG and/or PMSG treatment by immunofluorescence and immunogold cytochemistry. For the latter, immunoreagents and fixative were delivered directly to chilled, unfixed ovaries by in situ vascular perfusion. Data from biochemical and structural analyses indicated that hepatic lipase was absent from nonhormone-treated ovaries. As shown by Western blotting of ovarian effluent, the enzyme appeared following treatment with PMSG and PMSG-hCG; it increased in amount in a time-dependent manner, with a transient decline in the early hours after hCG injection. Enzyme levels paralleled growth and vascularization of follicles and corpora lutea; the fall tended to coincide with early events in luteal angiogenesis. Immunogold microscopy showed that hepatic lipase was abundant in thin-walled blood vessels of theca interna of follicles, corpora lutea, and interstitial cells but sparse in those of the stroma. Moreover, during neovascularization of differentiating corpora lutea, vascular sprouts arising from hepatic lipase-laden thecal vessels appeared to lose, then regain, the enzyme as development progressed. Our findings thus suggest 1) that hormones influence the establishment of endothelial cell heterogeneity within the microvasculature of a single organ and 2) that development of novel endothelial cell properties in specific subsets of blood vessels underlies compartmentalization of function within a tissue. PMID- 8465985 TI - Distribution of dystrophin and neurofilament protein in muscle spindles of normal and Mdx-dystrophic mice: an immunocytochemical study. AB - Dystrophin is a high molecular weight protein localized under the sarcolemma of normal extrafusal muscle fibers but absent in skeletal muscle of Duchenne muscular dystrophy patients and mdx mice. Muscle spindles in the soleus of 32 week-old normal and age-matched mdx mice were examined by immunocytochemical methods to determine the localization of dystrophin in polar and equatorial regions of the intrafusal fibers. Spindles were serially sectioned in transverse and longitudinal planes, and were double-labelled with an antibody to dystrophin and with an antibody to a 200 kD neurofilament protein, which revealed their sensory innervation. By fluorescence microscopy, intrafusal fibers in the soleus of mdx mice were deficient in dystrophin throughout their lengths, whereas their sensory nerve terminals stained intensely with the nerve-specific antibody and appeared unaltered in dystrophy. In the normal soleus, intrafusal fibers displayed a regional variability in the distribution of dystrophin. Polar regions of bag and chain fibers exhibited a peripheral rim of sarcolemmal staining equivalent to that seen in the neighboring extrafusal fibers. Dystrophin labelling in equatorial regions of normal intrafusal fibers, however, showed dystrophin-deficient segments alternating in a spiral fashion with positive staining domains along the sarcolemma. Double-labelling for dystrophin and neurofilament protein showed that these dystrophin-deficient sites were subjacent to the annulospiral sensory nerve wrappings terminating on the intrafusal fibers. These findings suggest that dystrophin is not an integral part of the subsynaptic sensory membrane in equatorial regions of normal intrafusal fibers and thus is not directly related to sensory signal transduction. The complete absence of this protein in mdx intrafusal fibers indicates that these fibers exhibit the same primary defect in muscular dystrophy as seen in the extrafusal fibers. However, because of their small diameters, capsular investment, and relatively low tension outputs, dystrophic intrafusal fibers may be less prone to the sarcolemmal membrane disruption that is characteristic of extrafusal fibers in this disorder. PMID- 8465986 TI - Blood-urine barrier formation in mouse urinary bladder development. AB - Formation of the blood-urine permeability barrier in differentiating mouse transitional urothelium was studied. It was established that the development of superficial cell barrier is a two-phase process: beginning with formation of the tight junctions, followed by formation of fusiform vesicles and asymmetric apical plasma membranes. Fusiform vesicles differentiate during days 15 and 17 of gestation and fuse with the apical plasmalemma. Thus a thick membrane is formed before the excretion of hypertonic urine into the embryonic bladder. Through some degenerative superficial cells slough between fetal day 17 and the day of birth, the bladder epithelium in mice does not lack an effective permeability barrier. PMID- 8465987 TI - Morphometric analysis of intact sperm heads and of sperm nuclei in the mouse. AB - A morphometric analysis of mouse sperm and of their nuclei was undertaken to investigate their respective post-testicular maturation. Sperm were collected from the testis, caput and cauda epididymidis, and their corresponding nuclei were isolated. Results indicate that the post-testicular maturation of sperm is distinct from that of nuclei. The size of intact sperm heads increases in the caput followed by a subsequent decrease in the cauda. In contrast, sperm nuclei decrease progressively in size. In general, a greater magnitude and number of alterations in intact heads and nuclei occur while in transit from the testis to the caput than during passage to the cauda epididymis. These results suggest that the period immediately following their release from the testis is crucial to the complete morphological maturation of sperm heads and nuclei. PMID- 8465988 TI - Basement membrane formation and re-distribution of the beta 1 integrins in a human intestinal co-culture system. AB - We have developed a co-culture system suited for the study of epithelial mesenchymal interactions in the human fetal small intestine. As the epithelial component of this model, we used the human intestinal cell line Caco-2 that is unique in its property to differentiate in vitro into a mature fetal enterocyte like cell type. A sheet of human intestinal mesenchymal cells, which we derived from an 18-week-old fetus, was used as mesenchymal element. Expression and distribution of cell-specific markers (cytokeratin 18 and dipeptidyl peptidase IV), major basement membrane components, and beta 1 integrins were analyzed. In 14-day co-cultures, Caco-2 cells formed a cytokeratin 18-positive epithelial-like sheet covering the vimentin-positive HIM cell layers. As assessed by brush border dipeptidyl peptidase IV expression, co-cultured Caco-2 cells achieved cytodifferentiation as when cultured on plastic. A complete deposition of all known major human fetal intestinal basement membrane components occurred at the Caco-2/HIM interface. Type IV collagen and tenascin were produced from the mesenchymal compartment, whereas laminin and fibronectin were contributed by both cell types. Interestingly, synthesis and deposition of basement membrane heparan sulfate proteoglycan were exclusively observed in co-cultures, suggesting modulation of epithelial expression of this molecule by HIM cells. Finally, we observed that epithelial integrin-beta 1 chains redistributed at the basal domain of co-cultured Caco-2 cells. Taken together, these observations indicate that the Caco-2/HIM co-culture model is a valuable system to study in vitro human basement membrane formation in the context of intestinal epithelial-mesenchymal interactions. PMID- 8465989 TI - Intercellular communication within the rat anterior pituitary gland: V. Changes in cell-to-cell communications as a function of the timing of castration in male rats. AB - Cell-to-cell communication by gap junctions was investigated in the male rat anterior pituitary gland following several experimental regimens involving castration. The regimens included the following animals: (1) Group 1, castrated at 10-day intervals from day 10 to 50 and sacrificed at 60 days of age; (2) Group 2, castrated every 10 days from days 10 to 50 and sacrificed 50 days after castration; (3) Group 3, castrated at 5 days of age and sacrificed every 10 days from day 10 to 60; or (4) Group 4, remained intact and sacrificed every 10 days from days 10 to 60. In all of the castrated animals, numerous so-called castration cells were scattered throughout the pars distalis of the pituitary gland, with occasional "signet ring cells" being observed. In Groups 1 and 2, the pattern of gap junction development and their number was no different from the intact control (Group 4). In contrast, the number of gap junctions in the animals castrated on day 5 remained very small even into adulthood. These data demonstrate that gonadal steroids are important in the initial development of gap junctions within the pituitary gland but are not necessary to sustain their presence once an animal becomes an adult. PMID- 8465990 TI - Ultrastructure of the human anogenital "sweat" gland. AB - A newly described type of cutaneous gland occurring in the human anogenital region was investigated in specimens from the vulva by electron microscopy. This gland, which is characterized by a long excretory duct opening at the skin surface, by a wide coiled secretory part with multiple lateral extensions in the form of diverticula and branches lined by a two-layered pseudostratified epithelium of myoepithelium, and by a luminal layer of tall columnar cells with conspicuous "snouts," could not be categorized as an eccrine, apocrine, or mammary gland. Electron microscopy confirmed its separate position by showing that the luminal layer of secretory cells with prominent cytoplasmic caps had elaborately folded lateral membranes, occasional canaliculi, and a large number of uniform electron-lucent to moderately electron-dense secretory granules as part of a probable merocrine secretion. The excretory duct showed a poorly developed cuticular border. This combination of ultra-structural features is alien to the other tubular cutaneous glands. The function of this anogenital "sweat" gland remains obscure, but the presence of these granules suggests a secretion product that is different from that of other cutaneous glands. PMID- 8465991 TI - Monoclonal antibodies identifying subsets of ectodermal, mesodermal, and endodermal cells in gastrulating and neurulating avian embryos. AB - The goal of our laboratory research is to elucidate the mechanisms underlying gastrulation and neurulation, using the avian embryo as a model system. In previous studies, we used two approaches to map the morphogenetic movements involved in these processes: (1) we constructed quail/chick transplantation chimeras in which grafted quail cells could be identified within chick host embryos by the presence of nucleolar-associated heterochromatin, and (2) we microinjected exogenous cell markers. However, it would be advantageous to be able to detect endogenous markers to demarcate various subsets of cells within the unmanipulated embryo. To elucidate such a series of natural markers, we have used monoclonal antibodies to identify epitopes found on subsets of ectodermal, mesodermal, and endodermal cells. Antibodies were made by immunizing mice against either homogenized ectoderm (i.e., prospective neural plate and surface ectoderm) or primitive streak, which had been microdissected from stage 3 chick embryos. Additionally, we screened a panel of antibodies made against soluble protein obtained from isolates of cell nuclei from late embryonic chick brain. Here, we describe the labeling patterns of three monoclonal antibodies, called MAb-GL1, GL2, and GL3 (GL, germ layer), during avian gastrulation and neurulation. Our results show that labeling early avian embryos with monoclonal antibodies can reveal previously undetected distributions of cells bearing shared epitopes, providing new labels for subsets of cells in each of the three primary germ layers. PMID- 8465992 TI - Isolation of chick primordial germ cells from stages 4-8 embryos. AB - Chick embryo primordial germ cells (PGCs) stages 4-8 were manually isolated for the first time from the late hypoblast layer. They were confirmed to be PGCs by periodic acid-Schiff (PAS) staining and examination by scanning electron microscopy (SEM). They were subsequently introduced onto a variety of artificial substrata. On two dimensional substrata, the cells change from a spherical shape covered with numerous microvilli to a rounded cell with a "skirt" of cytoplasm. Eventually a process projects from one side of the smooth cell. On a three dimensional substrate the PGCs change from a spherical shape covered with numerous microvilli to a smooth surfaced cell with a long single process. It is concluded that the PGCs which are originally spherical in situ in stage 4 alter their morphology both in vivo during their migration and in vitro studies. PMID- 8465993 TI - Foveal topography in the optic nerve and primary visual centers in Falconiforms. AB - The topography of the retinal nasal and temporal foveal projections upon the optic nerve and primary visual centers was studied in diurnal bifoveate birds of prey by means of restricted tritiated proline intraocular injection. According to the degree of retinotopy, this study reveals that a single injection of tracer in the nasal or temporal fovea produces a well-defined and complementary pattern of projections in the following contralateral nuclei: lateral anterior thalamus, lateroventral geniculate nucleus (glv), superficial synencephalic (ss), tectal grey (gt), and optic tectum. In the thalamic nucleus dorsolateral anterior, the nasal foveal projections are seen mainly in the lateral and rostrolateral subdivision, while temporal projections are seen mainly in the magnocellular subdivision. In the external and ectomammillary nuclei there is some evidence of retinotopic innervation. Finally, a discrete field of projection from the nasal or temporal fovea is detected in lateral hypothalamus, ventrolateral thalamus, lateral geniculate intercalated nucleus, and pretectal optic area. The nasotemporal axis of the retina is ventrodorsally oriented in the optic nerve with ganglion cell axons of the temporal fovea more dorsally placed than the nasal ones. In the primary visual centers this retinal axis is mediolaterally represented in the nuclei glv, ss, and gt, and dorsoventrally oriented in the optic tectum. PMID- 8465994 TI - Breed and seasonal variation of plasminogen activator activity and plasminogen activator inhibition in spermatozoa and seminal plasma of the ram in correlation with testosterone in the blood. AB - Plasminogen activator activity (PAA) and plasminogen activator inhibition (PAI), against t-PA (t-PAI) or u-PA (u-PAI), in spermatozoa and seminal plasma as well as testosterone in the blood of Friesland, Chios, and Karagouniki rams all showed a seasonal variation with the highest values during the corresponding breeding season of the ewes (Autumn-Winter). The seasonal variation of PAA and PAI in spermatozoa or seminal plasma as well as blood testosterone was different among the three breeds studied. Increased spermatozoal PAA was observed in November and May in Friesland rams, in October and November in Chios rams, and in October in Karagouniki rams. Spermatozoal t-PAI was increased in December and June in Friesland rams, in November and December in Chios rams, and in November in Karagouniki rams. Spermatozoal u-PAI was increased in December in Friesland rams, in October and December in Chios rams, and in November and December in Karagouniki rams. Plasminogen activator activity and PAI in seminal plasma also showed similar seasonal variations. Plasminogen activator activity and PAI in spermatozoa and seminal plasma showed a positive correlation with blood testosterone. The results of the present study support our previous findings on the possible role of spermatozoal PAA and PAI in the fertilizing ability of spermatozoa. PMID- 8465995 TI - Human sperm acrosin activity with relation to semen parameters and acrosomal ultrastructure. AB - It was suggested that although not related to the standard semen parameters the level of the acrosin enzyme system is related to the fertility potential in men. Recently a simple clinical assay for total acrosin level was recommended for routine semen analysis. The improved clinical assay was analysed on the freshly liquified semen of 198 Asthenoteratozoospermic men and compared with the routine semen parameters including biochemical data and the ultrastructure of the acrosome. Only the sum of the per cent of live, motile, and normal-shaped spermatozoa had positive significant and reasonably high correlation with the acrosin level (r = 0.382, P < 0.0001). Each characteristic exhibits significant but low (< 0.35) correlation. Similarly negative significant and reasonably high correlation was obtained between the acrosin level and the sum of the principle acrosomal malformations observed by TEM (r = 0.396, P < 0.0001) while lower negative correlation was found only with agenesis or loss of the acrosome. Acrosin levels below 8.1 microIU 10(-6) cells were obtained in 4 specimens with above 80% round-form associated with more than 95% of agenesis of the acrosome. The possible significance of the low correlation obtained between the acrosin levels and seminal plasma zinc levels, malformations in the acrosomal equatorial region, and the presence of white blood cells is also discussed. We concluded that the acrosin activity reflects an aspect of male fertility which is not diagnosed by the routine semen analysis or by the ultrastructure of the acrosome, and is therefore a useful diagnostic sperm parameter. PMID- 8465996 TI - A motile human sperm head fixation method. AB - In a solution containing less than 5% seminal fluid, human sperm has a tendency to attach its head on the smooth surface of an object. Based on such a phenomenon, a simple method was developed to fix sperm head on the surface of glass slide. This method was demonstrated by studying caffeine effect on the tail movement of human sperm in phosphate buffered saline. By analysing the images recorded on a videocassette, caffeine, a well known stimulator of human sperm motility, was shown to induce an immediate increase of sperm TBF (tail beat frequency) and the amplitude of TBF increase was found to be larger in sperm with lower basal TBF value. This method can provide a flock of head-fixed motile sperm for a precise sperm tail movement assessment or for other purposes. PMID- 8465997 TI - Influence of peritoneal fluid from spontaneous and stimulated cycles on sperm motility in vitro. AB - Peritoneal fluids (PFs) from spontaneous (n = 14) and gonadotrophin-stimulated cycles (n = 20) were obtained during diagnostic laparoscopy and gamete intrafallopian transfer (GIFT) procedures, respectively. The effects of these fluids on the linear component of sperm motility and on the percentage of motile spermatozoa were studied in vitro by objective motility assessments and compared to a control medium (B2-Menezo). Overall, the two types of PFs were found to have rather similar effects on the motility parameters studied. However, the fluids from hormonally-stimulated cycles sustained motility better (i.e., sperm velocity and percentage of motile sperm) and in a rather constant manner as a function of time (narrower range distributions of the motility measurements). Furthermore, it was observed that under identical experimental conditions motility measurements depended not only on the type of PF used but also on the sperm sample. These results suggest that assisted reproduction procedures in which PF is the medium where the gametes eventually meet and interact, such as direct peritoneal insemination (DIPI) or peritoneal oocyte and sperm transfer (POST), could have different success rates if performed in spontaneous rather than in stimulated cycles. At the same time, our results may help to explain why different pregnancy rates were reported in different studies using DIP or POST. PMID- 8465998 TI - Lack of HLA-molecules on human spermatozoa and in seminal plasma. AB - The expression of human leukocyte antigens (HLA) on ejaculated spermatozoa and on lymphocytes was compared by flow cytometry using monoclonal antibodies towards HLA class I (pan-HLA-A, -B, -C) and class II (DR) antigens. Soluble antigens of HLA class I (s HLA-A, -B, -C) in seminal plasma and in blood plasma were monitored with an ELISA technique. Lymphocytes showed specific fluorescence after incubation with the antibodies against HLA class I and class II (DR), whereas, on spermatozoa no positive immunofluorescence could be detected. No antibodies were bound to any significant extent either after modifications of sperm preparation (density gradient centrifugation, swim up-technique, addition of azide, foetal calf serum or benzamidine chloride) or after treatment of spermatozoa with detergents. Furthermore, different concentrations of soluble HLA-A, -B, -C in seminal plasma and in blood plasma were detected. The latter one showed soluble HLA about four-fold more concentrated than the seminal plasma (means +/- SD: 262.5 +/- 144.4 nmol l-1 vs. 62.5 +/- 27.1 nmol l-1). These results suggest, that the HLA-expression differs between human spermatozoa and somatic cells. PMID- 8465999 TI - Molecular organization of the plasma membrane in the post-acrosomal region of some farm animals. AB - According to the distribution of IMP, three different regions can be recognized on PF of the post-acrosomal plasma membrane of bull, ram, and boar spermatozoa. They are: (1) a region with linear aggregation of IMP, (2) a region with fewer and scattered IMP, and (3) a region with more numerous IMP. In the last two regions IMPs are randomly distributed or a clustering of certain particles is visible. In stallion spermatozoa the last two areas are undistinguishable. There are evident interspecies differences in the arrangement of linear aggregations of IMP which are characteristic for each species. PMID- 8466000 TI - Ultrastructural and immunocytochemical study of P1 protamine localization in human testis. AB - Two monoclonal antibodies (MAbs) directed against human protamine P1 were realized. Anti-P1 specificity was assessed by western-blot and confirmed by ELISA. Monoclonal antibody 97-3 was selected. Protamine P1 was specifically demonstrated in human testis by immunoelectron microscopy, using 97-3 MAb and an indirect post-embedding immunogold technique. Our results clearly demonstrated the precise time of appearance of P1 protamine in the nuclei of human spermatids. P1 first appeared in the nucleus of step 5 spermatids and its concentration was increased in steps 6-8 spermatids, cytoplasm was not labelled. PMID- 8466001 TI - Anesthesia and health care reform in 1993. PMID- 8466002 TI - What are the normal levels of cerebral blood flow and cerebral oxygen consumption during cardiopulmonary bypass in humans? PMID- 8466003 TI - Identification of patients at risk for excessive blood loss during coronary artery bypass surgery: thromboelastography versus coagulation screen. AB - In light of the potential morbidity associated with transfusion of blood products, a reliable preoperative screening test to identify cardiothoracic surgical patients who are at potential risk for increased intraoperative blood loss would be useful. Accordingly, we examined the efficacy of a variety of coagulation tests to predict intraoperative blood loss in 60 patients presenting for coronary artery bypass surgery (CABG). A complete coagulation screen, activated clotting time (ACT), and thromboelastograph (TEG) were performed before surgery. Intraoperative blood loss was determined by weighing sponges and measuring the quantity of blood in suction canisters. The duration of cardiopulmonary bypass was 100 +/- 4 min, and total surgery time was 5.0 +/- 0.1 h. Total crystalloid and colloid requirements were 5.5 +/- 0.2 and 1.4 +/- 0.1 L. Forty-eight percent of the patients required blood with an average requirement of 2.5 +/- 0.5 units. Total intraoperative blood loss averaged 1590 +/- 95 mL with a range from 640 to 3928 mL. Using multiple linear regression, all coagulation and TEG variables were used to model perioperative blood loss. Results showed that all components of the TEG failed to predict blood loss (r < 0.25, P > 0.78). However, three components of the routine coagulation assay, including bleeding time, prothrombin time, and platelet count could be modeled to predict perioperative blood loss (r = 0.75, P < 0.05). Although TEG has been shown to have potential in identifying postcardiopulmonary bypass coagulopathies, these results suggest that it does not appear to be useful in determining the coagulation status of CABG patients preoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466004 TI - The effect of epidural/general and cervical plexus block anesthesia on activated clotting time in patients undergoing vascular surgery. AB - The effect of anesthetic induction and surgical incision on activated clotting time (ACT) was determined in patients undergoing vascular surgery. Patients undergoing carotid endarterectomy (CAE) (n = 50) and abdominal aortic aneurysm repair (AAA) (n = 45) were studied. Patients in the CAE group had cervical plexus block anesthesia, whereas patients in the AAA group had a combination of epidural and general anesthesia. The ACT was measured 1) before induction of anesthesia, 2) 5 min after induction, 3) 5 min after incision, 4) 5 min after heparinization, and 5) at the onset of skin closure. Heparin was reversed with protamine only if the ACT after revascularization was > 200 s. Reversal was considered adequate if the ACT was < 200 s and the surgeon felt that hemostasis was adequate. The ACT decreased by 12.26 +/- 1.23 (mean +/- SE) (P = 0.006) in the CAE group and by 12.47 +/- 1.01 (P = 0.002) in the AAA group with induction of anesthesia. There was a further decrease of 5.06 +/- 0.62 (P = 0.26) in the CAE group and 5.17 +/- 0.83 (P = 0.22) in the AAA group with incision. There was a significant difference in ACT in both groups from postinduction and postincision to skin closure (higher at skin closure). No patient in either group required additional protamine or clotting factors post-operatively, or return to the operating room for excessive bleeding. This study demonstrates that anesthetic induction with cervical block or epidural/general anesthesia decreases ACT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466005 TI - Prophylactic nitroglycerin infusion during noncardiac surgery does not reduce perioperative ischemia. AB - We evaluated the impact of prophylactic nitroglycerin on the incidence of perioperative myocardial ischemia in patients with known or suspected coronary artery disease who undergo noncardiac surgery. Our goals were to better define the role of nitroglycerin in the management of high-risk patients and to explore the mechanisms of perioperative myocardial ischemia. Patients were assigned randomly to either a control group (n = 23) or to receive 0.9 micrograms.kg-1.min 1 of intravenous nitroglycerin (n = 22). The diagnosis of myocardial ischemia was based on a review of Holter electrocardiogram (ECG) recordings. There was no difference in the incidence of ischemia between groups. Seven control patients (30%) and seven nitroglycerin patients (32%) exhibited ECG evidence of ischemia. The preponderance of myocardial ischemia occurred during emergence from anesthesia (of the 14 patients exhibiting ischemia, 12 did so at emergence). There was an acute increase in heart rate at the onset of ischemia in all patients exhibiting ischemia with 14 of 18 episodes associated with an increase of 20% or greater. The heart rate associated with the onset of ischemia was greater in the nitroglycerin-treated patients than in the control group. We also found that the occurrence of myocardial ischemia on a preoperative Holter recording was strongly predictive of the subsequent occurrence of perioperative ischemia. In conclusion, the addition of nitroglycerin to standard anesthetic management of these high-risk patients does not measurably reduce perioperative ischemia. PMID- 8466006 TI - Direct or modified Seldinger guide wire-directed technique for arterial catheter insertion. AB - Percutaneous radial artery cannulation is widely used for direct continuous arterial blood pressure measurement and sampling of arterial blood. We compared the success rate of arterial catheter placement in patients undergoing aortocoronary bypass operations using the direct and the modified Seldinger techniques. The effects of gender and quality of the pulse were also investigated. Our study group consisted of 42 female and 96 male patients. The overall success rate with the guide wire was 82% compared with that of the direct method of 65% (P = 0.02). The success rate for arterial cannulation in male patients was high whether direct cannulation or a guide wire was used. In female patients, on the other hand, the failure rate with the direct technique was high (57%) and was significantly lower (14%) when the guide wire was used (P < 0.001). We conclude that the success rate for cannulation is high in male patients, and patients with a bounding pulse regardless of the use of the direct or guide-wire techniques. The guide wire is recommended as the initial technique for cannulating the radial artery of female patients. In patients with a thready pulse, no significant advantage could be obtained by using a guide wire, but in salvaging an arterial line the guide wire is efficacious. PMID- 8466008 TI - Actions of volatile anesthetics on ischemic and nonischemic Purkinje fibers in the canine heart: regional action potential characteristics. AB - The effects of halothane, isoflurane, and enflurane on proximal (false tendon) and distal (apical) Purkinje fibers were measured in vitro in infarcted canine hearts to assess their effects on action potentials of fibers located within the nonischemic and ischemic regions, respectively. High- and low-dose anesthetic effects were evaluated in three groups of eight preparations and compared to changes occurring at identical times in eight infarcted control preparations. Under control conditions in all groups, the action potential duration at 90% repolarization (APD90, mean +/- SEM) of ischemic distal fibers (396 +/- 9 ms) was longer (P < or = 0.01) than that of nonischemic proximal fibers (344 +/- 5 ms) and the ischemic fibers exhibited (P < or = 0.05) reduced maximum diastolic potential, amplitude, and Vmax relative to nonischemic fibers. Halothane (0.25 and 0.6 mM), isoflurane (0.4 and 0.8 mM), and enflurane (0.8 and 1.6 mM) produced dose-dependent decreases of nonischemic fiber APD90 with less decrease (P < or = 0.01) of ischemic fiber APD90 and thereby accentuated (P < or = 0.05) regional differences of APD90 at high dose. The decreases of nonischemic fiber APD90 were greater (P < or = 0.01) for 0.8 mM (2.9 minimum alveolar anesthetic concentration [MAC]) isoflurane (-95 +/- 5 ms) and 1.6 mM (2.5 MAC) enflurane (-79 +/- 12 ms) than for 0.6 mM (2.2 MAC) halothane (-41 +/- 3 ms). Isoflurane increased the pathologic difference (ischemic > nonischemic) between the repolarization times (APD90) of Purkinje fibers in the infarcted heart more (P < or = 0.05) than halothane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466007 TI - Actions of halothane and isoflurane on Purkinje fibers in the infarcted canine heart: conduction, regional refractoriness, and reentry. AB - The actions of halothane (HAL) and isoflurane (ISO) on conduction and regional refractoriness were studied in infarcted canine hearts to compare their effects on reentry in vitro. In two anesthetic groups of 8 hearts, high and low dose effects were assessed using action potentials recorded from Purkinje fibers located in the nonischemic and ischemic regions. An extrastimulus technique was used to determine the relationship between delay of conduction of premature impulses into the more refractory ischemic region and induction of reentrant responses. At high doses (HAL 0.60 mM and ISO 0.64 mM, approximately 2.3 minimum alveolar anesthetic concentration [MAC]) both anesthetics decreased (P < or = 0.05) the effective refractory period for direct intracellular stimulation of nonischemic fibers (local ERP, initial control: 294 +/- 8 ms); the decrease with HAL (-29 +/- 6 ms) was smaller (P < or = 0.05) than with ISO (-50 +/- 7 ms). HAL and ISO also decreased (P < or = 0.05) the coupling interval of the earliest premature impulse which conducted into the infarct (system effective refractory period [SERP], control: 301 +/- 7 ms) by -31 +/- 11 and -44 +/- 8 ms, respectively. In contrast, the functional refractory period (FRP) in the ischemic region (control:354 +/- 4 ms) was increased by HAL (26 +/- 8 ms; P < or = 0.05) but decreased by ISO (-14 +/- 4 ms, P < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466009 TI - Halothane and the reperfusion injury in the intact animal model. AB - We studied the effect of halothane on regional myocardial function during acute ischemia and reperfusion in an open-chest pig model. Anesthesia was induced with thiopental and fentanyl and maintained with an intravenous (IV) infusion of pentobarbital and fentanyl. Regional myocardial function was studied with microsonometers placed in the subendocardium supplied by the left anterior descending coronary (LAD) and circumflex coronary artery (LX). Systolic function was evaluated with reference to the end-systolic pressure-length relationship (ESPLR) and regional systolic shortening. Diastolic dysfunction was studied with postsystolic shortening (PSS). Ischemia was induced with 15 min of total occlusion of the LAD artery, and thereafter reperfusion was allowed for 120 min. Five groups were studied: one group received only pentobarbital and fentanyl (n = 10); the other groups received halothane 0.2% (n = 5), 0.4% (n = 7), 0.6% (n = 5), and 0.8% (n = 5). The pentobarbital and fentanyl infusion was adjusted in the halothane groups in an effort to maintain arterial blood pressure and heart rate within specified limits (when possible). Results indicate that regional dysfunction during acute ischemia was equal among all the groups. However, on reperfusion, halothane significantly reduced the incidence of ventricular arrhythmias. Halothane (0.6% and 0.8%) was associated with less regional postischemic systolic dysfunction during reperfusion when compared to the other groups. Hearts subjected to 0.6% and 0.8% halothane also were less stiff at the end of systole (i.e., the extrapolated ventricular volume at zero ventricular pressure was less) after 120 min reperfusion compared to animals receiving less halothane. However, diastolic dysfunction was equal among the groups during reperfusion. We conclude that, in this model, administration of halothane is associated with improved recovery of regional systolic function and potentially beneficial pressure-length relations at the end of systole after acute severe myocardial ischemia and reperfusion. Furthermore, administration of halothane was associated with fewer reperfusion arrhythmias compared to animals not receiving halothane. PMID- 8466010 TI - Progesterone-mediated potentiation of spinal sufentanil in rats. AB - Pregnancy is associated with an increased sensitivity to both general and local anesthetics. The exact reason is uncertain, but increased concentrations of progesterone and endogenous opiates have been implicated. Therefore, we tested the ability of intrathecally administered progesterone to produce analgesia and to potentiate the effects of spinal sufentanil. Female rats had intrathecal catheters implanted for drug administration, and analgesia was measured using the tail flick assay or hemostat clamp test. Animals were pretreated first with 10 micrograms, 20 micrograms, or 40 micrograms of intrathecal progesterone (n = 5, for each dose) and then given a minimally analgesic dose of sufentanil. Pretreatment with progesterone potentiated sufentanil's effect and resulted in almost complete analgesia. In contrast, in animals not pretreated with progesterone, the same dose of sufentanil resulted in minimal analgesia (n = 15). Intrathecal progesterone alone had no analgesic effects. No behavioral or motor effects were noted after progesterone treatment. Cerebral spinal fluid progesterone levels were within physiologic range. Furthermore, 100 micrograms of progesterone administered intramuscularly did not potentiate sufentanil analgesia. A major progesterone metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, 5 micrograms, 10 micrograms, or 20 micrograms (n = 5, for each dose), also potentiated sufentanil analgesia when administered intrathecally. In contrast, a stereoisomer, 5 beta-pregnane-3 beta-ol-20-one failed to show potentiation. Finally, two drugs that block gamma-aminobutyric acid-mediated increases in chloride ion conductance, picrotoxin and bicuculline, each blocked progesterone mediated potentiation of sufentanil analgesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466011 TI - Influence of sensor site location on pulse oximetry kinetics in children. AB - A pulse oximeter sensor is used to monitor changes in arterial hemoglobin oxygen saturation (SpO2) in anesthetized pediatric patients. The authors compared the kinetics of desaturation and resaturation measured by sensors placed over central (tongue, cheek) and peripheral (finger, toe) vascular beds in children with congenital heart disease. Desaturation time was defined as the time which elapsed between the onset of apnea and a 4% decrease in SpO2 from baseline. The desaturation times averaged 24 +/- 12 s, 56 +/- 34 s, and 58 +/- 28 s for the cheek, finger, and toe, respectively (n = 40; P < 0.0001 for cheek versus finger or toe). Resaturation time was defined as the interval between the resumption of ventilation and a 4% increase in SpO2 above the nadir. Resaturation times averaged 12 +/- 8 s for the cheek, 40 +/- 36 s for the finger, and 47 +/- 25 s for the toe (n = 40; P < 0.0001 for cheek versus finger or toe). A comparison of the kinetics at two central sensor sites, cheek and tongue, respectively, revealed no significant differences in desaturation times (20 +/- 10 s vs 21 +/- 9 s) or resaturation times (10 +/- 6 s vs 7 +/- 3 s) (n = 13). The authors conclude that both desaturation and resaturation are detected earlier by centrally placed sensors. PMID- 8466012 TI - Anesthetic management of patients undergoing bilateral unifocalization. AB - We report on the anesthetic management of eight patients undergoing unifocalization for pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries. Unifocalization was performed separately on the right and left lungs in the lateral decubitus position. During unifocalization, pulmonary blood flow to the nondependent lung is interrupted and arterial oxygenation is dependent solely on the blood flow to the dependent lung. Thus, PaO2 and SaO2 decreased significantly and PaCO2 increased significantly during unifocalization, as compared with before and after unifocalization. When these values are compared between first and second stage of unifocalization, SaO2 during second stage was lower than during first stage. Although PaO2, PaCO2, and pH during second stage tended to be worse than during first stage, the differences did not reach statistical significance. During unifocalization, especially in second stage, to prevent deterioration of these arterial gas variables, pulmonary blood flow had to be increased by frequent administration of catecholamine. In addition, bicarbonate infusion was also used to prevent progressive metabolic acidosis due to hypoxia during unifocalization. Because anticoagulant therapy was required during unifocalization, airway bleeding was a common complication. PMID- 8466013 TI - Propofol infusion and the incidence of emesis in pediatric outpatient strabismus surgery. AB - A prospective, randomized, double-blind study was conducted to examine the effect of a propofol infusion on the incidence of postoperative emesis in children undergoing outpatient strabismus surgery. Seventy-eight children, aged 3-12 yr, were allocated randomly to receive either nitrous oxide and halothane or nitrous oxide and a propofol infusion for the maintenance of anesthesia. The overall incidence of vomiting during the first 24 h was 64% in those receiving halothane and 41% in those receiving the propofol infusion; this difference was statistically significant (P < 0.05). In children who received no opioids postoperatively, the incidence of vomiting in the first 24 h was 71% in the halothane group and 24% in the propofol group; this difference was also significant (P = 0.001). We conclude that propofol was effective in reducing the incidence of postoperative emesis in pediatric outpatient strabismus surgery. PMID- 8466014 TI - Factors influencing deep vein thrombosis following total hip arthroplasty under epidural anesthesia. AB - To determine intraoperative factors which may influence deep vein thrombosis rate, we studied surgeries performed by one surgeon on 441 consecutive patients undergoing primary total hip arthroplasty under epidural anesthesia. Operative limb venography was performed on the fourth or fifth postoperative day in 381 patients, who received 650 mg of aspirin daily as the only postoperative thromboprophylaxis. Of 381 (15%) patients, 58 had a positive venogram; 13 (3%) had proximal thrombi. Of 178 patients (9.5%) with surgery lasting less than 70 min, 17 developed deep vein thrombosis whereas 41 of 203 patients (20.3%) with surgery lasting more than 70 min developed deep vein thrombosis (P < 0.05). Corresponding proximal deep vein thrombosis rates increased from 1.7% to 4.9%. Deep vein thrombosis was observed in 12.5% of patients receiving intravenous low dose epinephrine, 10.3% receiving intravenous sodium nitroprusside, 14.5% receiving both low-dose epinephrine and sodium nitroprusside concurrently, and 25% receiving intravenous fluid alone. Proximal deep vein thrombosis rates were 2.4%, 0%, 1.45%, and 9.3% in these groups, respectively. These data suggest that the intraoperative management of both surgery and anesthesia influence rates of deep vein thrombosis following total hip arthroplasty. PMID- 8466015 TI - Norepinephrine prolongs tetracaine spinal anesthesia in surgical patients: a preliminary study. AB - We conducted a double-blinded examination of the effects of norepinephrine as a vasoconstrictor on the onset and duration of tetracaine spinal anesthesia in 80 surgical patients. The patients were randomly allocated to four groups (n = 20 in each group). Each patient received 10 mg of tetracaine in a volume of 2.0 mL which contained either 0 micrograms/mL, 5 micrograms/mL, 10 micrograms/mL, or 15 micrograms/mL of norepinephrine. The onset of spinal anesthesia was determined by the time to reach Th-10 level as well as by the time required to obtain the highest level of sensory analgesia. The time for two-segment regression and full motor recovery were defined as the duration of spinal anesthesia. The time to reach Th-10, the highest analgesia level, and the time to obtain the highest analgesia level did not differ among the groups. Two-segment regression was prolonged significantly by 175%, 103%, and 106% as compared with the plain tetracaine group, in 5 micrograms/mL, 10 micrograms/mL, and 15 micrograms/mL of norepinephrine groups, respectively. Motor recovery also was extended significantly by 111%, 152%, and 121% as compared with the plain tetracaine group, in 5 micrograms/mL, 10 micrograms/mL, and 15 micrograms/mL of norepinephrine groups, respectively. There were no differences in the changes of arterial blood pressure and heart rate associated with the addition of norepinephrine among the groups. We conclude that norepinephrine provides a clinically meaningful prolongation of the duration of tetracaine spinal anesthesia. PMID- 8466016 TI - Subarachnoid local anesthetic block does not affect morphine absorption from paired intramuscular and subcutaneous injection sites in the elderly patient. AB - Morphine absorption from subcutaneous and intramuscular injection sites is dependent on local skin and muscle blood flow. Normally, drug absorption from intramuscular and subcutaneous injections at the same anatomical site is comparable, but spinal anesthesia alters muscle and skin blood flow in the blocked area. This study measured morphine absorption from pairs of intramuscular and subcutaneous injection sites at vastus lateralis and deltoid following a single dose of morphine sulfate in the presence of spinal anesthesia. Differences between the maximum concentration achieved after injection (Cmax) and the time at which this occurred (Tmax) were not significant when absorption for each "same site" pair of injections was compared, but Tmax after intramuscular injection at vastus lateralis was significantly longer than that observed following either intramuscular or subcutaneous injection at the deltoid (P < 0.05 for both comparisons). Cmax/Tmax ratios and the area under concentration time curve (AUC) also were analyzed, but there were no statistically significant differences among any of the four groups. PMID- 8466017 TI - Effect of gentle massage on regression of sensory analgesia during epidural block. AB - We investigated the effect of gentle epigastric massage on the regression of the sensory analgesia of epidural block. Sixteen patients, who underwent minor obstetric or gynecologic surgery under epidural block with lidocaine, were divided into two groups. Group A was the control group. Group B received gentle massage of the epigastric area for 30 min. The proximal extent of sensory analgesia before massage and 0 and 30 min after the massage was T9 +/- 1, T10 +/- 1, and T10 +/- 1 in group A, and T9 +/- 1, T11 +/- 1 and L1 +/- 1 in group B (mean +/- SD), respectively. The regression of sensory analgesia in group B was significantly (P < 0.001) faster than in group A 30 min after the massage. We conclude that peripheral sensory stimulation as weak as gentle massage may initiate a series of indirect mechanisms that lead to accelerated regression of sensory analgesia. PMID- 8466018 TI - Dose-response effect of intrathecal alfentanil on canine lower urinary tract dynamics. AB - The effect of intrathecal (IT) administration of three different doses (1, 2.5, and 5 micrograms/kg) of alfentanil on lower urinary tract dynamics was examined by urodynamic studies, cystometrograms (CMG), and urethral pressure profiles (UPP) in seven anesthetized dogs. Simultaneous serum drug concentrations were determined by specific radioimmunoassay for time-response analysis. A significant dose-dependent relaxation of urethral musculature expressed by a reduction in UPP values of 41.5% and 38.4% (P < 0.03) was noted 30 min after 5 and 2.5 micrograms/kg IT alfentanil, respectively, whereas the decrease of 13.4-22% in mean CMG values was not significant. All changes in UPP and CMG returned to baseline values by 60 min. The pharmacokinetics of alfentanil from the cerebrospinal fluid to the systemic circulation were linear, i.e., dose independent with maximal serum concentrations of 0.6, 1.4, and 3.5 ng/mL 10 min after the three respective IT doses. The low serum alfentanil concentrations and the lack of time correlation between the peak values and the changes in urinary tract activity, point to a spinally mediated mechanism. The short-lived effect of IT alfentanil on lower urinary tract dynamics and the relaxation of the bladder neck allow for unobstructed micturition pathways and may avoid urinary retention. PMID- 8466020 TI - The utility of tracheal temperature monitoring. AB - Tracheal temperature--the temperature of the tracheal wall--is believed to reflect the core temperature. The trachea reacts quickly to temperature changes because it is surrounded by various large arteries and veins. Using the blood temperature from the cardiopulmonary bypass (CPB) and the jugular vein temperature as standards for core temperature, we evaluated the utility of monitoring the tracheal temperature during cardiac surgery. The tracheal temperature was measured by a thermistor which was attached to the anterior inner surface of the cuff of a tracheal tube. The tracheal temperature had correlation coefficients more than 0.99 with both blood temperature from the CPB (r = 0.993, P < 0.001) and jugular vein temperature (r = 0.993, P < 0.001) during CPB. Because the blood from the CPB draining into the ascending aorta and the jugular vein temperature might reflect the hypothalamic temperature directly, the tracheal temperature, which correlates with both of these quite closely, may reflect the core value directly. The monitoring of the tracheal temperature is not only valuable in monitoring the core value, but is also convenient during general anesthesia. PMID- 8466019 TI - Loss of hypoxic ventilatory response following bilateral neck dissection. AB - Modified radical neck or combined radical and modified radical neck surgery is performed for treatment of head and neck cancer. Because of the extensive nature of the surgery, including dissection around the carotid vessels, we prospectively evaluated hypoxic ventilatory responses preoperatively and postoperatively in five patients. The change in ventilation to percent desaturation varied between 0.22 and -0.60 L/min per percent desaturation in the five study patients. In the postoperative evaluation, two of five patients showed flattened responses compared with the preoperative measurements due to denervation of their carotid bodies. Two patients showed increased responses due to loss of upper airway resistance from tracheostomy. We conclude that after bilateral neck dissection for cancer surgery some patients may lose their hypoxic ventilatory responses due to carotid body denervation. PMID- 8466021 TI - Can an anesthesia machine flush valve provide for effective jet ventilation? AB - Transtracheal jet ventilation (TTJV) using a percutaneously inserted intravenous (IV) catheter for the patient who cannot be ventilated or tracheally intubated or, using a jet stylet for changing endotracheal tubes (ETT) in patients for whom subsequent ventilation and/or tracheal reintubation may be difficult, are extremely valuable therapeutic options. The jet ventilation system must have a sufficiently high pressure-oxygen source to drive oxygen through noncompliant tubing and through relatively small IV catheters and/or jet stylets in order to achieve adequate ventilation and oxygenation. There is no evidence that using the common gas outlet of an anesthesia machine by activating the flush valve can provide enough flow (V) and tidal volume (VT) for effective jet ventilation. This in vitro study utilized a mechanical lung model that had a varying lung compliance [Cset (10-100 mL/cm H2O)] to determine the VT (measured by integrating a pneumotachograph flow signal) and corresponding minute ventilation (VE) through 14-, 16-, and 18-gauge IV catheters and small, medium, and large jet stylets. The flow of O2 was generated by activating the flush valve of Drager Narkomed 2 and 2A and Ohmeda Modulus II and II Plus anesthesia machines at an inspiratory:expiratory (I:E) ratio = 1:1 (unit of time = 1 s). We found that the largest VT and resultant VE were consistently obtained by activating the flush valve of the Ohmeda Modulus II and Drager Narkomed 2 anesthesia machines. The smallest VT and VE were produced using the Ohmeda Modulus II Plus anesthesia machine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466022 TI - Vancomycin does not enhance hypotension under anesthesia. AB - The rapid administration of vancomycin is associated with flushing and hypotension, a consequence of histamine release. The manufacturer discourages administering vancomycin to anesthetized patients, stating that vancomycin aggravates the hypotensive effects of anesthetics. To test this, we randomly assigned 36 adults (ASA classes I through III) to one of two groups: preinduction (Preind, n = 19) and postinduction (Postind, n = 17). Both groups received two different infusions: vancomycin (1 g/250 mL normal saline) and saline (250 mL normal saline) over 30-60 min. The Preind group received vancomycin before anesthesia was induced and saline was administered immediately after anesthesia was induced; for the Postind group, this order was reversed. This was done in a double-blind fashion. The anesthetic induction was standardized by the intravenous administration of thiopental and vecuronium and anesthetic maintenance by inhalation of nitrous oxide and enflurane. End-tidal enflurane, heart rate (HR), and blood pressure (BP) were measured every 3 min. Independent (unpaired) t-test was used in data analysis. The groups did not differ significantly. We conclude that vancomycin infusion may be given under anesthesia without significant adverse hemodynamic consequences if administered over a 30-60 min period of time. PMID- 8466023 TI - A-3665, a new short-acting opioid: a comparison with alfentanil. AB - A-3665 is a new short-acting synthetic opioid of the piperidine class. We conducted a double-blind, escalating dose comparison of A-3665 to alfentanil and placebo. Analgesic efficacy was assessed after the administration of A-3665 in increasing intravenous doses (0.25, 0.5, 1, 2, 4, 8, 16, 32, and 64 micrograms/kg) to nine groups of volunteers. At the lower doses (0.25, 0.5, 1, and 2 micrograms/kg), five volunteers were in each group; four received A-3665 and one received placebo in a double-blind manner. There were nine volunteers in each of the next three groups; four received A-3665 (4, 8, or 16 micrograms/kg), four received alfentanil (4, 8, or 16 micrograms/kg), and one received placebo. At the 32 micrograms/kg and 64 micrograms/kg dose levels, five subjects each were to be enrolled (four to receive A-3665 and one to receive placebo); however, the study was terminated after two subjects in the 64 micrograms/kg group had significant respiratory depression. Both drugs caused potent analgesia, compared with placebo, with peak effect occurring 3 min after injection. There was no significant difference in analgesic potency of A-3665 and alfentanil as measured by tolerance to tibial pressure at 3 min. At the dose of 16 micrograms/kg, both drugs significantly increased pain tolerance to tibial pressure compared with placebo at 3 min, but alfentanil continued to display significant analgesic effect versus placebo and versus A-3665 at 6, 11, and 15 min after injection. A 3665 caused significant respiratory depression at doses of 32 micrograms/kg and 64 micrograms/kg, but alfentanil did not induce significant respiratory depression at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466024 TI - Inhibitory effects of propofol on cytochrome P450 activities in rat hepatic microsomes. AB - The effects of propofol on cytochrome P450 activity in rat hepatic microsomes were evaluated to determine the potential influence of this anesthetic on the metabolism of coadministered agents. In microsomes from untreated and isoniazid treated rats, propofol was a weak inhibitor of enflurane metabolism, inhibiting activity only at 0.35 mM propofol. In contrast, toluene, a related compound, effectively impaired enflurane defluorination in microsomes from untreated, and isoniazid- and phenobarbital-treated rats at concentrations as low as 0.025 mM. Propofol, in contrast to toluene, was an effective inhibitor of benzphetamine demethylation where it inhibited this activity at propofol concentrations as low as 0.025 mM in microsomes from phenobarbital-treated rats. In microsomes from phenobarbital-treated rats, propofol potently inhibited the metabolism of aniline. Sixty-four percent inhibition was achieved at 0.03 mM propofol, whereas toluene had no effect at 1 mM. These data demonstrate that propofol does not effectively inhibit enflurane metabolism performed by the isoniazid-inducible cytochrome P450IIE1 but effectively impairs activities of the phenobarbital inducible cytochrome P450 isozymes. PMID- 8466025 TI - Propofol attenuates the myogenic response of vascular smooth muscle. AB - The myogenic response is the tendency of certain vessels, most notably small arteries and arterioles, to constrict in response to an increase in intravascular pressure. The effects of propofol on the myogenic response of the isolated pressurized rabbit ear artery were studied in segments preconstricted either with norepinephrine or 5-hydroxytryptamine and subjected to pressure increases from 60 to 100 mm Hg applied either rapidly (jumps over 500 ms) or slowly (ramps over 120 s). In the control experiments the preconstricted vessels initially dilated, then rapidly returned toward their initial diameter. In response to pressure ramps, vessels slowly dilated, but closely retained their resting diameter. Administration of propofol (1.6 x 10(-4) to 1.6 x 10(-3) M) resulted in dilation of the constricted vessels. With pressure jumps vessels had a reduced capacity to recover their initial diameters, and with pressure ramps vessels dilated to greater diameters. When the concentration of vasoconstrictor was increased to antagonize the propofol-induced dilation the myogenicity was not restored. This attenuation of myogenicity, distinct from the drug's vasodilator effect may represent a further mechanism by which anesthetic agents can affect cardiovascular function. PMID- 8466026 TI - Evaluation of STAT-CRIT hematocrit determination in comparison to Coulter and centrifuge: the effects of isotonic hemodilution and albumin administration. AB - The accuracy of the STAT-CRIT hematocrit (hct) was compared to Coulter and centrifuge methods in this study of the interrelationship between non-red cell blood constituents and accuracy of conductivity-based hct measurements. In the first part of the study, blood samples from 31 patients undergoing elective cardiac procedures were analyzed at three times: before induction of anesthesia (Time 1), during the rewarming period of cardiopulmonary bypass (CPB) (Time 2), and after transfusion of all cell-saver blood available after termination of CPB (Time 3). Laboratory evaluation included hct using the Stat-Crit, Coulter, and centrifuge methods, and sodium (Na), potassium (K), chloride (Cl), white blood cell count, total protein (TP), and albumin. In the second part of the study, patients were randomized to receive either 5% albumin (n = 14) or isotonic crystalloid (n = 14) after termination of CPB to determine the effect of protein colloid replacement on conductivity-based hct measurements. Blood samples were obtained before and after fluid volume replacement for multivariate analysis. Correlation of Coulter hct (absolute) with microhematocrit by centrifuge at all times (n = 93) was 0.95 (R2) with a bias and precision of -0.26 +/- 1.7%. Blood variables having the most significant effect on the Coulter-Stat-Crit difference (bias) were protein, Cl, and Na. Single regression analysis indicated that a 1 g/dL decrease in TP resulted in an absolute decrease in the hct reading by 1 hct% units. A 10-mmol/L change in either Cl or Na concentration resulted in a change in Stat-Crit accuracy of 3.5% and 2.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466027 TI - Bronchospirometry and separate measurement of occlusion pressure before and after lung resection using a double-lumen endotracheal tube. AB - To assess the distribution of ventilation to each lung, we measured ventilation and maximum negative airway pressure during occluded inspiratory effort (Pmax) of the individual lungs in eight male patients immediately before and after right upper lobectomy using a double-lumen endotracheal tube at a constant depth of enflurane anesthesia (end-tidal concentration 1.7%). Compared with the breathing pattern observed immediately before surgery, minute ventilation, Pmax, and respiratory frequency significantly increased immediately after the surgery, whereas tidal volume was unchanged. Bronchospirometry revealed that tidal volumes on the nonoperated side significantly increased after the operation. In contrast, tidal volumes on the operated side significantly decreased after the operation and were associated with significantly smaller Pmax obtained from unilateral airway than those of the nonoperated side postoperatively. These results indicate that there are considerable differences in ventilatory function between the lungs on the operated side and nonoperated side. The lung on the nonoperated side can partially compensate for the impaired ventilatory function on the operated side. PMID- 8466028 TI - Costs of anesthesia. PMID- 8466029 TI - Cerebral blood flow and metabolism during cardiopulmonary bypass. AB - Although much has been learned about cerebral physiology during CPB in the past decade, the role of alterations in CBF and CMRO2 during CPB and the unfortunately common occurrence of neuropsychologic injury still is understood incompletely. It is apparent that during CPB temperature, anesthetic depth, CMRO2, and PaCO2 are the major factors that effect CBF. The systemic pressure, pump flow, and flow character (pulsatile versus nonpulsatile) have little influence on CBF within the bounds of usual clinical practice. Although cerebral autoregulation is characteristically preserved during CPB, untreated hypertension, profound hypothermia, pH-stat blood gas management, diabetes, and certain neurologic disorders may impair this important link between cerebral blood flow nutrient supply and metabolic demand (Figure 5). During stable moderate hypothermic CPB with alpha-stat management of arterial blood gases, hypothermia is the most important factor altering cerebral metabolic parameters. Autoregulation is intact and CBF follows cerebral metabolism. Despite wide variations in perfusion flow and systemic arterial pressure, CBF is unchanged. Populations of patients have been identified with altered cerebral autoregulation. To what degree the impairment of cerebral autoregulation contributes to postoperative neuropsychologic dysfunction is unknown. It must be emphasized that not the absolute level of CBF, but the appropriateness of oxygen delivery to demand is paramount. However, the assumption that the control of cerebral oxygen and nutrient supply and demand will prevent neurologic injury during CPB is simplistic. A better understanding of CBF, CMRO2, autoregulation and mechanism(s) of cerebral injury during CPB has lead to a scientific basis for many of the decisions made regarding extracorporeal perfusion. PMID- 8466030 TI - Prolonged neuromuscular block after mivacurium in a patient with end-stage renal disease. PMID- 8466031 TI - Depression of neuromuscular function in a patient during desflurane anesthesia. PMID- 8466032 TI - Complete airway obstruction during arthroscopic shoulder surgery. PMID- 8466033 TI - Anesthetic management of the patient with a bronchogenic cyst: a review of 24 cases. PMID- 8466034 TI - Anesthetic considerations in patients with mitochondrial dysfunction. PMID- 8466035 TI - Coronary artery bypass grafting in a patient with multiple intracranial aneurysms and recent subarachnoid hemorrhage. PMID- 8466036 TI - Profound hypothermic circulatory arrest for noncardiac surgery via the closed chest technique. PMID- 8466037 TI - Cauda equina syndrome: a consequence of lumbar disk protrusion or continuous subarachnoid analgesia? PMID- 8466038 TI - Another iatrogenic cause of profound hypotension following cardiopulmonary bypass. PMID- 8466039 TI - Decimal dermatomes? PMID- 8466040 TI - Superior laryngeal nerve block as a supplement to total intravenous anesthesia for rigid laser bronchoscopy in a patient with myasthenic syndrome: risk of aspiration? PMID- 8466041 TI - Intranasal midazolam for rapidly sedating an adult patient. PMID- 8466042 TI - Oral midazolam in children: the effect at time and adjunct therapy. PMID- 8466043 TI - Migration of an epidural catheter related to flexion and extension of the spine. PMID- 8466044 TI - Gastric pH and stomach contents. PMID- 8466045 TI - Heart block in children. PMID- 8466046 TI - Not all breathing circuits are "circuits". PMID- 8466047 TI - Transdermal nicotine patch and general anesthesia. PMID- 8466048 TI - Evaluation of the change in your editorial policy. PMID- 8466049 TI - A lethal complication of internal jugular vein catheterization. PMID- 8466050 TI - "Migration" of an epidural catheter? PMID- 8466051 TI - Calculated risk of human immunodeficiency virus infection in anesthesiologists. PMID- 8466052 TI - Risk of HIV infection. PMID- 8466053 TI - Use of transcutaneous nerve stimulation to assist interscalene block. PMID- 8466054 TI - Throw away the chapstick. PMID- 8466055 TI - Oxygen flow reduction due to dust particle blockage of the oxygen filter. PMID- 8466056 TI - Rate-responsive pacemakers and extracorporeal shock wave lithotripsy: a dangerous combination? PMID- 8466057 TI - Calculating local anesthetic dose for infant spinal: body weight versus spinal length. PMID- 8466058 TI - Elective use in pediatric anesthesia of intraosseous infusion: proceed only with extreme caution. PMID- 8466059 TI - Neuromuscular stimulator causes changes in electrocardiograph tracing. PMID- 8466060 TI - Propofol sedation for pediatric MRI. PMID- 8466061 TI - Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations. AB - BACKGROUND: Muscle rigidity frequently accompanies induction of anesthesia with opioids. The authors sought to determine whether unconsciousness and amnesia occur when humans develop rigidity and apnea after intravenous fentanyl (without other concomitant anesthetics). METHODS: The incidence and duration of rigidity and level of consciousness were evaluated and associated plasma concentrations of fentanyl were measured in 12 healthy adult male volunteers given only intravenous fentanyl. Fentanyl was infused at a rate of 150 micrograms/min until a total of 15 micrograms/kg had been administered. Arterial blood samples for fentanyl assay were drawn and responsiveness, heart rate (HR), and systolic and diastolic arterial blood pressures were determined at frequent intervals during and after infusion. If rigidity was accompanied by an Spo2 < 90%, positive pressure ventilation with 100% O2 with a mask was instituted until spontaneous ventilation resumed. RESULTS: The incidence of muscular rigidity was 50% (6/12). All subjects who developed rigidity were apneic, unresponsive, and had no recall of commands to breathe or of positive pressure ventilation. Subjects not developing rigidity remained awake and responsive. No subject developing rigidity required neuromuscular blockade to allow positive pressure ventilation and adequate oxygenation (Spo2 > 90%). When rigidity occurred, it started 3 +/- 0.9 (range 1 4) min after the peak plasma fentanyl concentration and lasted for 11.5 +/- 5.8 (range 7-23) min. Rigidity started at a plasma fentanyl concentration of 21.5 +/- 4.4 (range 16-28) ng/ml and ended at 6.9 +/- 1.5 (range 5.2-8.7) ng/ml. Baseline HR was less in the subjects who subsequently developed rigidity (56.7 +/- 7.8 vs. 67.2 +/- 7.8 P = 0.04). No differences in fentanyl plasma concentrations or predicted effect site concentrations for rigidity were detected between subjects who developed rigidity and those who did not. CONCLUSIONS: These findings support the hypothesis that unconsciousness occurs in the unstimulated subject during fentanyl-induced apnea and rigidity. PMID- 8466062 TI - The effect of flumazenil on midazolam-induced depression of the ventilatory response to hypoxia during isohypercarbia. AB - BACKGROUND: While flumazenil reverses benzodiazepine-induced sedation, its ability to antagonize the ventilatory depressant effects of benzodiazepines has not been fully established. A randomized, double-blind study was conducted to determine whether flumazenil effectively reverses midazolam-induced depression of the hypoxic ventilatory response. METHODS: Twelve healthy male volunteers received intravenous midazolam 0.12 +/- 0.01 mg.kg-1 followed by either flumazenil 1.0 mg or placebo. Hypoxic ventilatory response was measured using an isocapnic rebreathing technique: as Spo2 decreased to 70% VE and tidal volume were continuously recorded. Hypoxic response determinations were performed before and after midazolam, as well as 3, 30, 60, 120, and 180 min after flumazenil or placebo. RESULTS: After midazolam, the slope of the hypoxic ventilatory response curve (VE vs. SpO2) decreased to 0.59 +/- 0.05 (means +/- SE) times its premidazolam baseline; likewise, at Spo2 = 90%, minute ventilation (VE90) and tidal volume (TV90) decreased to 0.70 +/- 0.04 and 0.62 +/- 0.03 times baseline, respectively. Three minutes after flumazenil, the slope increased to 1.10 +/- 0.13 times baseline (P < 0.05 vs. postmidazolam), while following placebo, it was only 0.81 +/- 0.09 times baseline (P = NS vs. postmidazolam, P < 0.05 between treatments). VE90 and TV90, after flumazenil, increased to 1.45 +/- 0.15 and 1.27 +/- 0.09 times baseline, respectively (P < 0.05 vs. postmidazolam); these increases were significantly greater than the corresponding changes observed after placebo (P < 0.05 between treatments). CONCLUSIONS: It was concluded that, after sedation with midazolam, flumazenil causes a greater increase in hypoxic ventilatory response during isohypercarbic conditions than does placebo, and may, therefore, be useful in the treatment of midazolam-induced ventilatory depression. PMID- 8466063 TI - Assessment of ketorolac as an adjuvant to fentanyl patient-controlled epidural analgesia after radical retropubic prostatectomy. AB - BACKGROUND: Opioids, although effective postoperative analgesics, are associated with undesirable side effects. In an attempt to determine whether adjuvant, nonopioid medication would permit a reduction of the amount of fentanyl required for postoperative analgesia, the efficacy of ketorolac, an injectable nonsteroidal antiinflammatory drug, was studied as an adjuvant to fentanyl patient-controlled epidural analgesia (PCEA) for postoperative pain management following radical retropublic prostatectomy. METHODS: Forty patients were randomized into two groups to receive fentanyl PCEA and either ketorolac 30 mg intramuscularly every 6 h after an initial dose of 60 mg (n = 20) or placebo (n = 20) for 72 h. Visual analogue scale pain scores (0-100 mm; 0 mm = no pain; 100 mm = worst pain), sedation, fentanyl usage, gastrointestinal function, complications, blood loss, and temperature were assessed four times each day. RESULTS: Visual analogue scale (VAS) pain scores at rest were lower in the ketorolac group during the first 4 h (P < 0.01), but were similar thereafter. Global VAS pain scores with activity were lower in the ketorolac group on postoperative day 1 (23 +/- 4 vs. 39 +/- 6; P < 0.05) and postoperative day 2 (17 +/- 3 vs. 29 +/- 4; P < 0.05). Bladder spasm pain occurred less frequently in the ketorolac group (1 vs. 9 patients; P < 0.05). Fentanyl usage was less in the ketorolac group throughout the study (33 +/- 3 vs. 50 +/- 6 micrograms/h, 0-24 h; 20 +/- 2 vs. 36 +/- 6 micrograms/h, 24-48 h; 12 +/- 2 vs. 24 +/- 6 micrograms/h, 48-72 h; P < 0.05). Sedation scores and side effects were similar, except on postoperative day 3 when nausea was less frequent in the ketorolac group (0 vs. 6 patients; P < 0.05). Recovery of gastrointestinal function occurred sooner in the ketorolac group as determined by first bowel sounds (26 +/- 3 vs. 38 +/- 4 h; P < 0.05), first clear liquids (51 +/- 2 vs. 65 +/- 3 h; P < 0.01), and first regular meal (95 +/- 4 vs. 110 +/- 4 h; P < 0.05). There was no significant difference in blood loss, transfusion requirement, hematocrit, platelet count, or temperature. There was high overall satisfaction in both groups, but fewer patients in the ketorolac group rated pain with walking as usually or always painful (1 vs. 9 patients; P < 0.05). CONCLUSIONS: Ketorolac is a beneficial adjuvant to fentanyl PCEA for postoperative pain management after radical retropubic prostatectomy. PMID- 8466064 TI - Continuous intravenous infusion of rocuronium (ORG 9426) in patients receiving balanced, enflurane, or isoflurane anesthesia. AB - BACKGROUND: Rocuronium (ORG 9426) is a new nondepolarizing neuromuscular blocking agent with a rapid onset and an intermediate duration of action. This study obtains the infusion requirements of rocuronium in 30 patients in whom anesthesia was maintained with barbiturate-nitrous oxide-opioid, nitrous oxide and enflurane, or nitrous oxide and isoflurane. METHODS: For all 30 patients, anesthesia was induced with intravenous thiopental and fentanyl, followed by 0.45 mg/kg rocuronium. Patients were randomly allocated to receive either: 1) nitrous oxide in 40% oxygen supplemented with fentanyl, thiopental, and droperidol (balanced anesthesia), 2) 1.25 MAC enflurane-nitrous oxide, or 3) 1.25 MAC isoflurane-nitrous oxide. Once blockade had recovered to 95% depression of twitch height, muscle relaxation was maintained by continuous infusion of rocuronium, adjusted to maintain mechanical twitch response at 95% depression. RESULTS: At 90 and 120 min, the enflurane and isoflurane groups had lower infusion requirements than those receiving barbiturate-nitrous oxide-opioid anesthesia (P < 0.02), but these did not differ significantly between the two volatile agents. Final infusion requirements (mean +/- SD) were 9.8 +/- 3.7, 5.9 +/- 3.1, and 6.1 +/- 2.7 micrograms.kg-1.min-1 for the groups receiving barbiturate-nitrous oxide opioid, enflurane, and isoflurane anesthesia, respectively. Spontaneous recovery began soon after termination of the infusion; in all patients, twitch tension equaled 10% of control within 5 min. CONCLUSIONS: The infusion requirements to maintain 95% twitch depression approximated 10 micrograms.kg-1.min-1 during barbiturate-nitrous oxide-opioid anesthesia. These requirements were reduced by 40% during anesthesia involving enflurane or isoflurane. PMID- 8466065 TI - The effect of cricoid pressure on preventing gastric insufflation in infants and children. AB - BACKGROUND: The use of cricoid pressure for the possible prevention of regurgitation of gastric contents during induction of anesthesia in both adults and children has been recommended. However, equally important is the technique in possibly preventing insufflation of gas into the stomach. This study was designed to determine the efficacy of cricoid pressure application in preventing gastric gas insufflation in pediatric patients and to determine the airway pressure at which gas entered the stomach (pop-off point). METHODS: Fifty-nine patients, 2 weeks to 8 yr of age, physical status 1-4, scheduled for elective surgery, received an inhalational induction of anesthesia with halothane, N2O, and O2. A single observer used a stethoscope to auscultate over the upper abdomen for any air entry. In study I (without paralysis), the proximal airway pressure was slowly increased by gradually closing the pop-off valve on the anesthesia machine until gas was heard entering the stomach (pop-off point) or until the peak inspiratory pressure (PIP) reached 40 cm H2O. Thereafter, the pressurization procedure was repeated three times, altering the application and removal of cricoid pressure. The same patients were then paralyzed (study II), and the stomach evacuated before commencing an identical pressurization sequence with and without cricoid pressure. RESULTS: Appropriately applied cricoid pressure was 100% effective in preventing gas insufflation into the stomach of all children up to 40 cm H2O PIP with and without paralysis. In addition, paralysis significantly decreased the median pop-off point in any given patient. CONCLUSIONS: Appropriate application of cricoid pressure prevents gastric gas insufflation during airway management via mask up to 40 cm H2O PIP in infants and children. An additional benefit of cricoid pressure occurs in paralyzed patients in whom gastric insufflation occurs at lower inflation pressures. PMID- 8466066 TI - Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharmacokinetic study. AB - BACKGROUND: The pharmacokinetic and pharmacodynamic properties of propofol indicate that this may be an appropriate agent for induction and maintenance of anesthesia in obese patients. This study was designed to assess the rates of recovery and the pharmacokinetics of propofol infusions in morbidly obese patients. METHODS: Anesthesia was induced and maintained using a stepwise infusion regimen of propofol in eight morbidly obese patients. The patients' lungs were ventilated with nitrous oxide:oxygen (66:34%). Pharmacokinetic parameters were calculated from iterative blood sampling during the propofol infusion and during 8 h after its completion. RESULTS: Results were compared with those from a concurrent study of propofol pharmacokinetics in nonobese adults. The initial volume of distribution of propofol was not modified in obese patients. Total body clearance increase was correlated to body weight (R = 0.76, 25.4 +/- 6.5 ml.kg-1.min-1, mean +/- SD). Volume of distribution at steady state was also correlated to body weight (R = 0.61, 1.63 +/- 0.54 l.kg-1, mean +/- SD). Propofol concentration at the time of eye opening in response to verbal command was 0.94 +/- 0.26 mg.l-1. CONCLUSIONS: Results from this study confirm the absence of propofol accumulation in morbidly obese patients when the current dosing scheme is used. Dosing schemes expressed in mg.kg-1 are the same as those in normal patients. PMID- 8466067 TI - Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus parenteral opioids. AB - BACKGROUND: Different types of analgesia have been proposed for the prevention of postoperative respiratory complications. The aim of this prospective, double blind randomized study was to compare the impact of epidural bupivacaine and opioids versus parenteral opioids on respiratory complications in patients who had undergone major abdominal surgery. METHODS: One hundred fifty-three patients undergoing abdominal surgery for cancer were randomly allocated to receive either general anesthesia with intravenous fentanyl and postoperative analgesia with subcutaneous morphine (SC group) or general anesthesia combined with epidural bupivacaine and epidural bupivacaine plus morphine for postoperative pain relief (EP group). Analgesia was tested on a visual analog pain scale. Pulmonary complications were evaluated according to clinical complications, chest radiographs, arterial blood gas analysis, and pulmonary function tests. The evaluation was carried out on the day before the operation and on the first 5 postoperative days. Particular attention also was paid to the episodes of arterial hypotension and hemoglobin oxygen desaturation during the 1st postoperative night. RESULTS: Pain relief was significantly better in the EP group than in the SC group (P < 0.05) especially during recovery and on the 1st and 2nd postoperative days. In the EP group, vital capacity decreased less on the 1st postoperative day (P < 0.05) and arterial oxygen tension was greater in the recovery room (P < 0.05). However, no statistically significant difference was observed between the SC and EP groups in the incidence of clinical pulmonary complications (31% and 27%, respectively) and radiographic chest abnormalities (52% and 46%, respectively). The EP group recovered intestinal function earlier (P < 0.05), but significantly more patients in this group had episodes of systolic hypotension (21% vs. 8%; P < 0.05) during the 1st postoperative night. The length of the hospital stay was similar in both groups of treatment. CONCLUSIONS: Epidural analgesia with a combination of local anesthetic and opioid improves patient comfort. However, this type of analgesia does not decrease the incidence of postoperative pulmonary complications, does not reduce the length of the hospital stay, and carries the risk of complications from episodic systemic hypotension. PMID- 8466068 TI - Insulin decreases the serum potassium concentration during the anhepatic stage of liver transplantation. AB - BACKGROUND: Severe hyperkalemia is a serious problem during orthotopic liver transplantation. The effectiveness of insulin in decreasing serum potassium concentration during the anhepatic stage of orthotopic liver transplantation was investigated. METHODS: Forty patients with serum potassium concentrations greater than 4.0 mM/L at the onset of the anhepatic stage were randomized into two groups. Control group patients (n = 20) received no treatment, and treatment group patients (n = 20) received an intravenous bolus of regular insulin (20 u) 10 min into the anhepatic stage, followed by a glucose infusion (500 ml 5% dextrose in water) over 15 min. RESULTS: In the control group, the potassium concentration did not change, whereas in the treatment group, it decreased from 4.70 +/- 0.54 to 4.18 +/- 0.63 mM/L (mean +/- SD) within 15 min and to 3.57 +/- 0.55 mM/L 60 min after therapy. The potassium concentration was less in the treatment group than in the control group within 30 min of treatment (3.97 +/- 0.52 vs. 4.49 +/- 0.43 mM/L, respectively; P < 0.05). The potassium concentration increased similarly 30 s after graft reperfusion in both groups of patients, but was less in the treatment group (5.91 +/- 1.63 vs. 7.37 +/- 1.67 mM/L, respectively; P < 0.05). The potassium concentration returned to prereperfusion levels within 5 min after graft reperfusion. CONCLUSIONS: In patients undergoing orthotopic liver transplantation, the administration of insulin rapidly decreases serum potassium concentration, even in the absence of the liver, suggesting an important contribution by extrahepatic tissues in the insulin-stimulated uptake of potassium. PMID- 8466069 TI - Approximate entropy of heart rate as a correlate of postoperative ventricular dysfunction. AB - BACKGROUND: Instantaneous changes in the heart rate, i.e., heart rate variation, traditionally have been quantified by the standard deviation of a series of intervals between successive heart beats. Approximate entropy provides another measure of variability by calculating the logarithmic likelihood that patterns that are similar remain similar on the next incremental comparisons. Approximate entropy is a nonnegative number that will distinguish data sets by their amount of regularity, with larger numbers indicating more randomness. We hypothesized that a decrease in the approximate entropy of heart rate would be associated with postoperative ventricular dysfunction (e.g., myocardial infarction, unstable angina, congestive heart failure, prolonged inotropic support). METHODS: Twenty three high-risk noncardiac patients were continuously monitored by ambulatory electrocardiographic recorders from the evening before surgery up to 80 h during the postoperative period: 9 demonstrated postoperative ventricular dysfunction, and 14 had an uncomplicated postoperative course. Hourly approximate entropy average values were calculated. RESULTS: Approximate entropy was high (> 0.7) in all but two patients preoperatively. Postoperative approximate entropy <0.55 had a sensitivity of 88% and a specificity of 71% for being associated with postoperative ventricular dysfunction; preoperative approximate entropy values were not significantly different between the two groups. CONCLUSIONS: These results suggest that changes in approximate entropy can distinguish between patients who sustained poor outcome and those who had an uncomplicated course. PMID- 8466070 TI - Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane. AB - BACKGROUND: Basal cytotoxic activity of NK cells, a subtype of lymphocytes involved in the nonspecific immune response to viruses, tumors, and some bacteria, is altered in the postoperative period. The current study examines the effects of halothane and isoflurane on interferon-induced stimulation of NK cell cytotoxicity in vivo and in vitro. METHODS: Mice were exposed to either anesthetic on days 10, 5, 1, or -1 relative to interferon treatment on day 0. NK cytotoxicity was assessed 24 h later. Similarly, splenic mononuclear cells containing NK cells were treated with interferon, before or after in vitro exposure with either halothane or isoflurane, and cytotoxicity was determined. RESULTS: In vivo, isoflurane or halothane inhibited subsequent interferon-induced NK cell stimulation (> 90% and 67%, respectively). No inhibition occurred if interferon was given before anesthetic exposure. Significant inhibition of interferon-induced NK cell stimulation could be observed 11 days after anesthesia. In vitro, both anesthetics inhibited the subsequent stimulation of NK cytotoxicity by interferon, however, cytotoxicity of NK cells treated with interferon before anesthetic exposure was comparable to untreated interferon stimulated NK cells. CONCLUSIONS: Halothane and isoflurane inhibit interferon stimulation of NK cytotoxicity in naive (unstimulated) NK cells of the splenic mononuclear cell pool without affecting the cytotoxicity of previously stimulated (interferon) NK cells. This could occur directly by preventing the NK cell from responding or indirectly by altering other cells in the splenic mononuclear cell pool (T cells, macrophages), which then inhibit NK cell induction. PMID- 8466071 TI - Anesthetic potency (MAC) is independent of forebrain structures in the rat. AB - BACKGROUND: The ability of general anesthetics to suppress somatomotor responses to surgical incision and other noxious stimuli is of particular clinical relevance. When the blockade is due to inhaled agents, this effect can be quantified as the minimum alveolar concentration (MAC), i.e., that concentration that blocks movement evoked by a noxious stimulus (ED50). METHODS: To identify the neural structures that subtend this somatomotor response, we anesthetized 14 rats with isoflurane in oxygen and performed bilateral parietal-temporal craniotomies. In each rat, MAC was repeatedly tested using tail-clamping and Dixon's up-down concentration technique. After determination of baseline MAC, seven rats underwent aspiration decerebration, after which MAC was repeatedly measured. RESULTS: In the control group (N = 7), MAC (mean +/- SD) remained constant at 1.30 +/- 0.25% for more than 6 h. In the seven rats that underwent aspiration decerebration, baseline MAC was 1.26 +/- 0.14%. These seven rats with histologically validated precollicular decerebration demonstrated no change in MAC relative to control rats, as much as 11 h after decerebration (P = 0.14). CONCLUSIONS: These findings suggest that the anesthetic-induced unresponsiveness to noxious stimuli measured by MAC testing does not depend on cortical or forebrain structures in the rat. PMID- 8466072 TI - The effects of ketamine on the excitation and inhibition of dorsal horn WDR neuronal activity induced by bradykinin injection into the femoral artery in cats after spinal cord transection. AB - BACKGROUND: It is now well established that wide dynamic range neurons (WDR) can possess widespread cutaneous inhibitory receptive fields, as well as excitatory receptive fields, in specific regions of the body. The ability of ketamine to depress the excitatory responses of spinal WDR neurons indicates that the analgesia produced by this agent may be a result, in part, of this spinal action. The primary purpose of this study was to investigate the effects of ketamine on the WDR propriospinal inhibitory mechanism that is induced by a bradykinin (BK) injection as a noxious test stimuli. METHODS: In decerebrate, spinal cord transected cats (L1-L2), the effects of a low (0.5 mg.kg-1, intravenous) and a high (10 mg.kg-1, intravenous) dose of ketamine on the neuronal activity of spinal dorsal horn WDR neurons evoked by femoral artery injection of BK (10 micrograms) was examined. Extracellular activity was recorded from single WDR neurons that responded to noxious and innocuous stimuli applied to the cutaneous receptive fields on the foot pads of the left hind paw. RESULTS: After ipsilateral BK administration, the activity of the WDR neurons was found to be increased (excited) in all ten neurons that were examined. In contrast, the activity of these neurons was found to be decreased (inhibited) in five of these ten neurons after BK administration into the contralateral femoral artery. The 10 mg.kg-1 dose of ketamine significantly suppressed the excitatory activity observed in all 15 of the WDR neurons examined. A comparison of the effects produced by the 0.5-mg.kg-1 and the 10-mg.kg-1 intravenous doses reveals that the amount of suppression was dose-related. In addition, the inhibitory WDR neuronal activity induced by contralateral BK injection was also significantly reduced by both the 0.5- and the 10-mg.kg-1 doses of ketamine. CONCLUSIONS: These results indicate that this reduction of excitatory and inhibitory responses of WDR neurons after noxious stimulation is likely to be the fundamental basis for the spinal cord component of ketamine-induced analgesia. PMID- 8466073 TI - High-dose droperidol protects against experimental coronary thrombosis in dogs and pigs and attenuates aggregation of porcine platelets and Ca2+ mobilization in human platelets. AB - BACKGROUND: Activation of platelets after contact with thrombogenic substrates may be an early factor leading to coronary artery thrombosis and myocardial infarction. Haloperidol, a butyrophenone, possesses weak in vitro platelet inhibitory activity. Experiments were designed to determine whether droperidol, a butyrophenone adjunct to anesthesia, protected against experimental coronary thrombosis in intravenously anesthetized open-chest dogs and pigs, attenuated ex vivo porcine platelet aggregation, and inhibited agonist-induced increases in [Ca2+]i in human platelets. METHODS: In dogs and pigs, a lesion consisting of deendothelialization, deep vessel wall injury, and critical stenosis was created in the proximal circumflex arteries, resulting in coronary thrombus formation accompanied by decreased circumflex artery blood flow. Embolization of the thrombus restored flow, but the cycle then repeated, resulting in repetitive cyclical flow reductions (CFRs). These were measured using an electromagnetic flow probe. RESULTS: In dogs, droperidol 0.2 mg/kg intravenous rapidly abolished CFRs in all ten animals, with frequency decreasing from 0.22 +/- 0.01 cycles/min to 0. Droperidol 0.8 mg/kg intravenous rapidly abolished CFRs in seven of eight pigs, with frequency decreasing from 0.15 +/- 0.01 to 0.02 cycles/min (P < 0.005). In both species, additional doses of droperidol were effective against CFRs augmented with intravenous epinephrine, a catecholamine that stimulates thrombosis. Ex vivo platelet aggregation studies were performed in platelet-rich plasma obtained from pigs before and after droperidol 0.8 mg/kg intravenous. Pretreatment with the drug resulted in marked inhibition of aggregation evoked by collagen, modest attenuation of that elicited by adenosine diphosphate (ADP), but no effect on that evoked by arachidonic acid. In human platelets, apparent [Ca2+]i was estimated using the fluorescent indicator indo-1 and flow cytometry. Droperidol 10(-7), 10(-6), and 10(-5)M had a dose-dependent inhibitory effect on the amplitude of increases in [Ca2+]i evoked by 10(-5)M serotonin (plus 10(-7)M epinephrine). The higher droperidol concentration decreased the response to as much as 30% of control (P < 0.001). Droperidol lacked effect on Ca2+ mobilization elicited with 10(-6)M ADP. CONCLUSIONS: The results from three experimental models indicate that droperidol attenuates experimental coronary thrombosis in animals and suggest that this inhibition may result, in part, from a direct droperidol depressant effect on platelet activation and aggregation. PMID- 8466074 TI - Pentobarbital-morphine anesthetic interactions in terms of intensity of noxious stimulation required for arousal. AB - BACKGROUND: Previous reports suggest that the outcome (synergism, antagonism, summation) of opioid-barbiturate interactions may depend on the depth of anesthesia. One aim of the present study was to determine whether pentobarbital, alone and in combination with morphine, blocks awakening caused by noxious stimulation in a dose-related manner: the more intense the noxious stimulation, the more pentobarbital is required to suppress the response. A second aim of the study was to determine whether the pentobarbital-morphine anesthetic interaction depends on the depth of anesthesia measured in terms of intensity of noxious stimulation required for behavioral arousal (recovery of the righting reflex). METHODS: Experiments were performed on rats, with the measure of anesthetic effect being suppression of the righting reflex. The noxious stimulus was pressure on the tail at four levels of intensity: 0.0, 0.25, 2.5, and 3.3 kg, generated with an Analgesy-Meter. Pentobarbital and morphine were injected intravenously via chronically implanted catheters. Dose-response curves for pentobarbital given alone and in combination with morphine were determined (by probit analysis) separately for each of the pressure levels. RESULTS: Pentobarbital, alone and in combination with morphine, blocked awakening caused by noxious stimulation of different intensities in a dose-related fashion so that more anesthetic was required to block awakening with more intense stimulation. The pentobarbital ED50 values were: 12.0, 19.5, 22.7, and 24.3 mg/kg for 0.0, 0.25, 2.5, and 3.3 kg pressure, respectively. The addition of morphine (1 mg/kg) reduced the pentobarbital ED50 values for 0.0, 0.25, and 2.5 kg pressure by 34% (P < 0.0001), 39% (P < 0.0001), and 21% (P < 0.005), respectively. No change was seen in the pentobarbital ED50 value at the maximal (3.3 kg) pressure level. CONCLUSIONS: The results suggest that the depth of anesthesia can be measured in terms of intensity of noxious stimulation required for arousal and that the outcome of barbiturate-opioid anesthetic interaction depends on the depth of anesthesia. PMID- 8466075 TI - Inhibition of dopamine transport in rat brain synaptosomes by volatile anesthetics. AB - BACKGROUND: Volatile anesthetics may depress transmission by altering synaptic concentrations of neurotransmitter. Microdialysis studies have found an increase in brain extracellular dopamine concentration on exposure to volatile anesthetics. We investigated the possibility that synaptosomal dopamine transport is reversibly inhibited by the halothane and isoflurane. METHODS: Rat brain synaptosomes were incubated with 5 nM 3H-DA and increasing concentrations of anesthetic in Teflon-sealed microvials. Cocaine (100 microM) was used to quantify non-specific binding/uptake. Uptake was stopped by vacuum filtration and washing; label incorporation into synaptosomes was determined by liquid scintillation counting. 3H-DA release from preloaded synaptosomes also was studied in the presence of the anesthetic to allow distinction between uptake inhibition and release stimulation in the synaptosomes. RESULTS: Both halothane and isoflurane inhibited the specific 3H-DA uptake in a concentration-dependent fashion with an IC50 of 0.72 +/- 0.14 mM for halothane and 2.24 +/- 0.85 mM for isoflurane. No stereoselectivity of isoflurane's action on Dopamine (DA) uptake was observed. The inhibition produced by halothane and isoflurane was kinetically characterized as noncompetitive, but full reversal was demonstrated after removal of the anesthetic from the incubation mixture. The anesthetics did not stimulate 3H-DA release from preloaded synaptosomes. CONCLUSIONS: These results demonstrate volatile anesthetic-induced inhibition of the dopamine transporter in this preparation of synaptosomes. The calculated IC50S suggest this inhibition occurs with clinically relevant concentrations of halothane but not with isoflurane. The results are consistent with and may explain the increase in extracellular dopamine concentrations demonstrated by microdialysis. PMID- 8466076 TI - Neostigmine produces bradycardia in a heart transplant patient. PMID- 8466077 TI - The failure of capnography to properly assess endotracheal tube location. PMID- 8466078 TI - Gadolinium-enhanced magnetic resonance imaging and autopsy findings in a patient with cauda equina syndrome. PMID- 8466079 TI - Lidocaine toxicity treated with low-dose propofol. PMID- 8466080 TI - Response to surgical stress following thoracic epidural anesthesia. PMID- 8466081 TI - Response to surgical stress following thoracic epidural anesthesia. PMID- 8466082 TI - A newly designed curved needle for percutaneous cannulation of the internal jugular vein. PMID- 8466083 TI - Potency versus onset of neuromuscular blocking agents. PMID- 8466084 TI - Use of neuromuscular relaxants in a child with an abnormal anatomy. PMID- 8466085 TI - Is it really free? PMID- 8466087 TI - Pharmacology of clonidine. PMID- 8466086 TI - Does diabetes reduce local anesthetic requirement? PMID- 8466088 TI - Preoperative epidural fentanyl, neuroplasticity, and postoperative pain. PMID- 8466089 TI - Evaluation of responses to pneumococcal vaccine. PMID- 8466090 TI - Immunosuppressive therapy for autoimmune diseases. PMID- 8466091 TI - Refractory wheezing and shortness of breath in a 34-year-old woman. PMID- 8466092 TI - Evaluation of postimmunization pneumococcal titers in children with recurrent infections and normal levels of immunoglobulin. AB - Seven children were evaluated who had recurrent sinusitis, acute otitis media, pneumonia, and mastoiditis. All children had normal or near normal levels of IgG, IgA, and IgM. One child displayed a poor antibody response following tetanus and diphtheria immunization. Another child was noted to be atopic as determined by allergy skin tests. A polyvalent pneumococcal vaccine was administered to all children after 24 months of age, with the average age of administration being 33 months. Titers were obtained 3 to 6 weeks following immunization and were evaluated to 12 serotypes using radioimmunoassay. All seven patients failed to mount an adequate response to immunization and were treated with a course of intravenous gammaglobulin. Five of seven children showed a distinct improvement in clinical course. Children with recurrent infections and normal levels of IgG may have a depressed ability to respond to pneumococcal antigen. Evaluation of their response to pneumococcal vaccine can be used as a marker to determine their ability to make antibody specific responses to multiple infectious agents. The failure to make a specific antibody response may be one factor in the susceptibility of these patients to recurrent infections. PMID- 8466093 TI - Antibody levels and response to pneumococcal vaccine in steroid-dependent asthma. AB - Immunization with pneumococcal vaccine is recommended for patients with chronic respiratory diseases, and is also used to evaluate antibody responses to polysaccharide antigens. We determined the effect of chronic prednisone treatment on immunoglobulin levels, pneumococcal antibody levels, and on the serologic response to pneumococcal vaccination. We studied 14 adult steroid-dependent asthmatics receiving daily or alternate day prednisone, 10 to 35 mg, and 14 age matched, nonsteroid dependent asthmatic patients. Immunoglobulin levels were within the normal range in all patients. There was no difference in the pre immunization antipneumococcal polysaccharide antibody levels against serotypes 3, 7F, 9N, and 14 between steroid-dependent and nonsteroid-dependent asthmatic patients. All patients had increases in antipneumococcal antibody levels 4 weeks after pneumococcal immunization. Mean post-immunization pneumococcal antibody titers were similar in steroid-dependent and nonsteroid-dependent asthmatic patients. All patients either had or developed levels > or = 300 ng Ab N/mL against one or more pneumococcal serotypes. We conclude that chronic prednisone treatment in steroid-dependent asthmatic adults does not significantly affect immunoglobulin levels, pneumococcal antibody levels, or specific antibody responses to pneumococcal immunization. PMID- 8466094 TI - Efficacy of laser-acupuncture in the prevention of exercise-induced asthma. AB - Many asthmatic patients are reluctant to follow the medication schedule prescribed for them and turn to alternative treatment methods. The results of this study indicate that one such method, laser acupuncture, does not prevent exercise-induced asthma. PMID- 8466095 TI - Comparison of the acceptability of the Ventolin metered-dose inhaler and the Bricanyl Turbuhaler. AB - One hundred fifty-nine asthmatic patients aged 19 to 76 years completed an open crossover-designed study comparing the acceptability of the Bricanyl Turbuhaler (BTH) and the Ventolin metered-dose inhaler (VMDI). The doses given were presumed to be equiactive. Each treatment period lasted for 14 days. Patients registered morning and evening peak expiratory flow rate (PEFR) before and five minutes after medication. Asthma symptoms as well as adverse events were registered on diary cards. After each study period a questionnaire containing acceptability questions was completed. At the end of the study the patients indicated their preference for one of the two treatments. The two treatments were equal concerning bronchodilation and asthma symptoms. There was an overall preference for the Bricanyl Turbuhaler. PMID- 8466096 TI - Effects of cetirizine versus terfenadine in seasonal allergic rhinitis. AB - The purpose of this study was to compare the efficacy and safety of cetirizine, 10 mg, once daily in the morning to terfenadine, 60 mg, BID in the treatment of seasonal allergic rhinitis. The multicenter, single-blind, parallel study involved 160 patients, who were all included in the safety and efficacy analysis. The results of the study showed that both cetirizine, 10 mg, QD and terfenadine, 60 mg, BID used for 1 week are safe and effective in the management of allergic rhinitis. By repeated measures analysis, cetirizine improved symptoms more than terfenadine for the treatment period of days four to seven. Standard Cochran Mantel-Haenszel statistics test showed the relative degree of patient satisfaction to be higher in the cetirizine group. PMID- 8466097 TI - Dose-response study of inhaled salmeterol in asthmatic patients with 24-hour spirometry and Holter monitoring. AB - Salmeterol is a new long-acting beta 2-selective adrenoceptor agonist. In this double-blind, 6-way crossover study, four single doses of salmeterol by metered dose inhaler (12.5, 25, 50, 100 micrograms) were compared with albuterol aerosol 200 micrograms and placebo in 24 patients with moderate asthma with 24-hour pulmonary function testing and Holter monitoring. Salmeterol was an effective bronchodilator at each dose evaluated and demonstrated a greater increase in FEV1 above baseline, a slightly slower onset and a longer duration of bronchodilation than albuterol. Median durations of bronchodilation were 9.0, 15.6, 13.4, and 18.4 hours with increasing doses of salmeterol in comparison to 4.2 hours for albuterol. Holter monitoring showed (1) a mean maximum heart rate 2 to 5 bpm higher after salmeterol 50 and 100 micrograms compared with placebo and (2) supraventricular premature beats (> 30 per hour or > 100 per 24 hours) more often in the salmeterol 100-micrograms group (13% to 17% of patients) than in the placebo (4%), albuterol (4% to 8%), or other salmeterol groups (4% to 9%). These differences were not statistically significant. Tremor and palpitations were the most frequently reported drug-related adverse events and their frequencies increased with increasing doses of salmeterol. This study demonstrated that single doses of salmeterol given by metered dose inhaler over an 8-fold range possess substantial, long-lasting bronchodilator activity. PMID- 8466098 TI - Cerebral lateralization and histamine skin test asymmetries in humans. AB - Although asymmetries exist in both cerebral and somatic systems, their relationship is not well understood. One hypothesis suggests that some processes determining cerebral hemispheric dominance also affect immune systems. We employed histamine, a final common mediator for the immediate hypersensitivity immune response, to examine the relationship of skin response to cerebral lateralization (ie, left versus right brain dominance). Histamine skin wheal responses on the left and right forearms were measured using computerized planimetry in 176 consecutive patients undergoing allergy skin testing. Cerebral lateralization was determined by personal and family handedness via questionnaires. Subjects were classified as right handed (RH) with only RH relatives, RH with non-RH relatives, or non-RH (ie, left-handed or ambidextrous). Left/right arm asymmetries in wheal area were demonstrated and were related to cerebral dominance, but could not be explained by simple arm use. Right-handed subjects with only RH relatives had greater wheal size on the right arm, RH subjects with non-RH relatives had no significant left/right difference in wheal size, and non-RH subjects had greater wheal size on the left arm. Further, gender differences in these asymmetries appeared to be present for subjects with mixed cerebral dominance. The results suggest an association between process affecting cerebral and somatic asymmetries, and offer new insight into brain/body interactions. PMID- 8466099 TI - Allergic bronchopulmonary aspergillosis in patients with and without evidence of bronchiectasis. AB - Allergic bronchopulmonary aspergillosis (ABPA) may complicate 1% to 2% of all cases of chronic asthma. Twenty-eight patients fulfilling the diagnostic criteria for ABPA but without evidence of proximal bronchiectasis [ABPA-S (seropositive)] were identified over a 12-year period and classified by stage. The majority of patients were in remission but all had chronic asthma. Serum anti-Aspergillus fumigatus (Af) IgG was lower in ABPA-S (n = 28) versus ABPA-CB (central bronchiectasis) (n = 58) at the time of initial presentation (IgG-Af index 3.62 versus 7.80, t = 3.46, P < or = .001). Serum IgG1-Af was significantly lower in ABPA-S as compared with ABPA-CB (t = 2.37, P = .011), as was serum IgG2-Af (t = 1.91, P = .031) and serum IgG4-Af (t = 1.78, P = .041). There were trends toward lower concentrations of total serum IgE, serum anti-Af-IgE, and anti-Af-IgA in ABPA-S. Eleven patients with ABPA-S were evaluated closely for a total of 63 patient-years and only four exacerbations with pulmonary infiltrates were identified. No patient in either group was observed to progress to end-stage or irreversible lung disease when early recognition and treatment were instituted. We conclude that ABPA-S represents the earliest stage or apparently a less aggressive form of ABPA. PMID- 8466100 TI - The value of screening for risk of exercise-induced asthma in high school athletes. AB - Exercise challenges were performed on 166 middle and high school student athletes (aged 12 to 18 years) to evaluate undiagnosed exercise-induced asthma (EIA). Seventy-three percent were male, 70% were white, and 30% were black. All students completed a questionnaire and were briefly interviewed to elicit risk factors for EIA. Resting spirometry, exercise treadmill provocation, and postexercise spirometry at 1, 10, 20, and 30 minutes were performed. Twenty-two students had reductions in FEV1 > or = 15% from baseline; 15 of these had FEV1 reductions > or = 20%. Of students considered at risk for EIA by history or baseline spirometry (N = 48, 29%) eight (17%) demonstrated EIA after exercise. Of students with no risk factors (N = 118, 71%), 14 (12%) demonstrated EIA after exercise, but would not have been identified without exercise challenge. The overall incidence of EIA was 12%, a rate that is consistent with previous studies of college and Olympic athletes. Sixty-four percent of students identified with EIA were not considered at risk by routine screening methods. History and spirometry alone may not be adequate as screening tools for EIA in adolescents. PMID- 8466101 TI - Expression of interleukin-6 in association with rat lung reimplantation and allograft rejection. AB - Organ transplantation has become a therapeutic option for the replacement of malfunctioning tissues and organs. Since the advent of the first combined heart lung transplant in 1981, there has been a rapid growth in the popularity of lung transplantation for a number of end-stage pulmonary disorders. Interestingly, these lung transplant patients experience more complications of acute and chronic allograft rejection compared with recipients of other solid organs. These episodes of rejection are related to a complex series of events that depend on the interaction of many cells and soluble mediators leading to cellular and tissue injury. The histopathology of lung allograft rejection has been actively studied and is associated with the sequestration of activated mononuclear phagocytes, T and B lymphocytes. These cells secrete a number of soluble mediators, that is, cytokines, that participate in the evolution of the immune response via autocrine, paracrine, or endocrine mechanisms. The interaction of cytokines with their targets leads to cellular activation, proliferation, and differentiation. In this study, we postulated that interleukin-6 (IL-6) may have a central role in the pathogenesis of acute lung allograft rejection. To test this hypothesis, we employed an unmodified RT1-incompatible rat lung allograft model and assessed the time course and major tissue compartment(s) of IL-6 production during the evolution of lung allograft rejection. The expression and production of IL-6 during the pathogenesis of lung allograft rejection was measured at the whole-animal, organ, cellular, and molecular levels. The expression of IL-6 was found to be bimodal in character, initially related to the reimplantation response and finally to the maximal allograft rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466102 TI - Histochemical evidence for induction of arachidonate 15-lipoxygenase in airway disease. AB - We have previously described the distribution of the arachidonate 15-lipoxygenase in lung tissue obtained from healthy human subjects. In the present study, we have utilized the same immunohistochemical methodology to examine the expression of 15-lipoxygenase in bronchial biopsy tissue from subjects with airway disease. Immunohistochemistry of bronchial tissue using two antibodies against distinct epitopes of the 15-lipoxygenase and indirect biotin-avidin-peroxidase detection demonstrated that, in contrast to airway tissue from normal subjects (n = 10) in which 15-lipoxygenase antigen was confined to the uppermost airways (nose and trachea) and was almost undetectable in bronchi, the bronchial tissue obtained from subjects with asthma (n = 7) or chronic bronchitis (n = 7) exhibited markedly positive immunostaining of mucosal epithelial cells with both anti-15 lipoxygenase antibodies. Specificity of 15-lipoxygenase immunostaining was verified by antigen competition experiments and by the lack of immunostaining with preimmune serum or control anti-5-lipoxygenase antibodies. The increased levels of 15-lipoxygenase antigen in the bronchial epithelial cells of asthmatic and bronchitic subjects compared with the same cell population in normal subjects coupled with the previous findings of increased 15-lipoxygenase activity in asthmatic airways suggest that epithelial 15-lipoxygenase is induced by airway inflammatory disease. PMID- 8466103 TI - Continuous venous air embolism in patients receiving positive end-expiratory pressure. AB - The occurrence of venous air embolism in critically ill patients can cause profound cardiopulmonary compromise. Recognized causes include aspiration through an indwelling catheter and pneumothorax. We report three patients in whom we found continuous air embolism in the inferior vena cava that persisted for days. The bubbles appeared to arise from splanchnic veins, and they were associated with barotrauma and positive airway pressure. In the two survivors, the bubbling ceased when the ARDS resolved and airway pressures were decreased. We suspect that venous air embolism is not an uncommon occurrence in critically ill patients receiving high positive airway pressure. PMID- 8466104 TI - HIV-1 and the lung. Infectivity, pathogenic mechanisms, and cellular immune responses taking place in the lower respiratory tract. PMID- 8466105 TI - Noninvasive ventilation. Does it work, for whom, and how? PMID- 8466106 TI - Guidelines for the evaluation of impairment/disability in patients with asthma. American Thoracic Society. Medical Section of the American Lung Association. PMID- 8466107 TI - Assessment of new sterilizing drugs for treating pulmonary tuberculosis by culture at 2 months. PMID- 8466108 TI - Plasma elastin peptide level, a diagnostic test for chronic obstructive lung disease? PMID- 8466109 TI - Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. PMID- 8466110 TI - New concepts in the formation of pulmonary edema. PMID- 8466111 TI - Recovery of pulmonary function in farmer's lung. A five-year follow-up study. AB - The recovery of pulmonary function in farmer's lung (FL) was studied during a 5 yr follow-up in 101 patients (20 men and 81 women, mean age 47 yr). At the initial evaluation all patients had the first diagnosed attack of FL. Spirometry, measurement of pulmonary diffusing capacity, and arterial blood gas analysis were done at the time of the diagnosis and 1, 3, 6, 12, and 24 months thereafter. The last follow-up measurements were made 4 to 6 yr after the initial evaluation. Mean FVC improved significantly for up to 1 yr. In mean DLCO there was improvement for up to 2 yr. Mean PaO2 rose to its maximum within 1 month of the initial examination and did not change significantly thereafter. No patient had diagnosed asthma at the time of the diagnosis of FL, but asthma was later diagnosed in 7 patients during the follow-up. In conclusion, the pulmonary function of FL patients improved for up to 2 yr after the initial acute episode. In general, PaO2 improved most rapidly; the improvement in FVC was slower, and the recovery of DLCO took the longest time. PMID- 8466112 TI - Important deficits of lung function in three modern colliery populations. Relations with dust exposure. AB - To determine whether dust-related "clinically important" deficits of lung function still occur in British coal miners we have analyzed the relationship between lifetime cumulative exposure to respirable dust and risk of defined functional deficits in a population of miners who were examined between 1981 and 1986. The study group consisted of a sample of men who had worked at any one of three collieries (South Wales, Yorkshire, and North East England) between 1970, when new dust standards were introduced, and date of medical survey. There were 1,671 men studied, including men who had left the collieries. "Clinically important" deficits of FEV1 from predicted values derived in this population were defined by comparisons with questionnaire data on exercise tolerance limited by breathlessness. The mean FEV1 of men in the South Wales colliery, for example, who said they had to stop for breath when walking at their own pace on level ground was 942 ml less than the predicted value for nonsmokers after taking age and stature into account. Individual cumulative exposures to respirable dust were calculated from a long-term program of measurements of dust concentrations and occupational records commencing in 1953. In the three colliery populations, 24, 24, and 12% in South Wales, Yorkshire, and the North East, respectively, had FEV1 deficits that were at least as severe as the average deficit associated with the severe grade of exertional dyspnea described above. In all collieries deficits were more common in smokers than in nonsmokers, and more common in men who had left the industry than in men still within it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466113 TI - The pulmonary response of white and black adults to six concentrations of ozone. AB - Many early studies of respiratory responsiveness to ozone (O3) were done on healthy, young, white males. The purpose of this study was to determine whether gender or race differences in O3 response exist among white and black, males and females, and to develop concentration-response curves for each of the gender-race groups. Three hundred seventy-two subjects (n > 90 in each gender-race group), ages 18 to 35 yr, were exposed once for 2.33 h to 0.0 (purified air), 0.12, 0.18, 0.24, 0.30, or 0.40 ppm O3. Each exposure was preceded by baseline pulmonary function tests and a symptom questionnaire. The first 2 h of exposure included alternating 15-min periods of rest and exercise on a motorized treadmill producing a minute ventilation (VE) of 25 L/min/m2 body surface area (BSA). After exposure, subjects completed a set of pulmonary function tests and a symptom questionnaire. Lung function and symptom responses were expressed as percent change from baseline and analyzed using a nonparametric two factor analysis of variance. Three primary variables were analyzed: FEV1, specific airway resistance (SRaw), and cough. Statistical analysis demonstrated no significant differences in response to O3 among the individual gender-race groups. For the group as a whole, changes in the variables FEV1, SRaw, and cough were first noted at 0.12, 0.18, and 0.18 ppm O3, respectively. Adjusted for exercise difference, concentration-response curves for FEV1 and cough among white males were consistent with previous reports (1). PMID- 8466114 TI - Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life. AB - The relationship between initial level of lung function and subsequent wheezing, lower respiratory illness (LRI) was studied in 97 infants in whom the first measurement of pulmonary function (PFT) was made before 6 months of age. Occurrence of LRI was evaluated by standardized questionnaires at each well-baby visit, biweekly telephone calls to mothers, and review of all visits to physicians. Infant PFT was assessed by partial expiratory flow-volume curves and helium-dilution measurement of functional residual capacity (FRC). Maternal, prenatal smoking was assessed by urine cotinine and standard questionnaires. Infants who developed an LRI during the first year of life had lower preillness length-corrected forced expiratory flow at FRC (VFRC) than those who did not experience an LRI (males, 2.06 +/- 0.20 versus 2.32 +/- 0.29 ml/s/cm; females, 2.38 +/- 0.20 versus 2.91 +/- 0.26 ml/s/cm). Similar results were observed with FRC-corrected VFRC. No differences were observed for FRC. Differences in lung function were greatest in female infants whose mothers did not smoke during pregnancy (VFRC 2.67 +/- 0.25 versus 3.49 +/- 0.26 ml/s/cm for those with and without LRI, respectively; p = 0.03). History of maternal wheezing was more common in infants who experience an LRI, independent of maternal smoking. The results were not influenced by exposure to nonmaternal sources of environmental tobacco smoke in the postnatal period. Regression analyses that included data for multiple measurements of VFRC over the first year and took account of duration of follow-up demonstrated that lower levels of VFRC were associated with an increased frequency of LRI, especially in female infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466115 TI - Predictors of individual differences in acute response to ozone exposure. AB - The purpose of this study was to identify personal characteristics that predict individual differences in acute FEV1 response to ozone exposure. Response and predictor data were collected on 290 white male volunteers 18 to 32 yr of age who were each exposed to one of six concentrations of ozone between 0.0 and 0.40 part per million. The sample was divided into an exploratory sample of 96 and a confirmatory sample of 194 subjects. Exploratory analysis indicated that ozone, age, and several other variables explained a significant proportion of the variance in response. In the confirmatory sample, only age and ozone concentration predicted FEV1 decrement. For the combined sample ozone explained 31% of the variance, with age accounting for an additional 4%. The model predicted a decreasing response with increasing age for all nonzero ozone concentrations. For exposure to 0.40 ppm, the model predicts decrements in FEV1 of 1.07 and 0.47 L for 18- and 30-yr-old subjects, respectively. We concluded that for white male subjects age was a significant predictor of response, with older subjects being less responsive to ozone. Furthermore, we demonstrated that exploratory analysis without control of type I statistical error rates may result in apparent findings that cannot be replicated. PMID- 8466117 TI - Measuring quality of life in asthma. AB - The aim of this study was to evaluate the measurement properties of an Asthma Quality of Life Questionnaire. The study design was an 8-wk unblinded single cohort with assessments at 0, 4, and 8 wk. Thirty-nine adults with symptomatic asthma and a wide range of airway responsiveness and medication requirements were enrolled from previous studies and through notices in the local media. Those with inadequately controlled asthma were offered an inhaled steroid (budesonide). Asthma Quality of Life Questionnaire, spirometry, a clinical asthma control questionnaire, medication requirements, airway responsiveness to methacholine, the Sickness Impact Profile, and the Rand questionnaire were recorded at each visit. Patients kept daily diaries of peak flow rates and medications. The Asthma Quality of Life Questionnaire was able to detect changes in patients who responded to treatment or who had natural fluctuations in their asthma (p < 0.001) and to differentiate these patients from those who remained stable (p < 0.001). The Questionnaire was reproducible in patients who were stable (intraclass correlation coefficient = 0.92). There were significant longitudinal and cross-sectional correlations between asthma quality of life and other measures of both clinical asthma and generic quality of life. We conclude that the Asthma Quality of Life Questionnaire has good measurement properties and that it is valid as both an evaluative and a discriminative instrument. It measures the component of asthma most important to patients, and it should be considered for inclusion in all asthma studies. PMID- 8466116 TI - Particulate air pollution and hospital emergency room visits for asthma in Seattle. AB - Recent studies have associated short-term exposure to respirable particulate matter (PM10) exposure with peak flow decrements, increased symptoms of respiratory irritation, increased use of asthma medications, and increased hospitalization for asthma. Increased mortality from chronic respiratory disease has also been reported. To help confirm whether PM10 exposure is a risk factor for the exacerbation of asthma, we compiled daily records of asthma emergency room visits from eight hospitals in the Seattle area. In Poisson regressions controlling for weather, season, time trends, age, hospital, and day of the week, the daily counts of emergency room visits for persons under age 65 were significantly associated with PM10 exposure on the previous day. The mean of the previous 4 days' PM10 was a better predictor (p < 0.005). The relative risk for a 30 micrograms/m3 increase in PM10 was 1.12 (95% confidence interval 1.20 to 1.04). Daily PM10 concentrations never exceeded 70% of the current ambient air quality standards during the period. The consistency of investigations of the health effects of PM10 suggest that increased attention should be given to the control of particulate matter air pollution. PMID- 8466118 TI - Intrinsic positive end-expiratory pressure in ambulatory patients with airways obstruction. AB - In patients with severe expiratory airflow limitation, dynamic hyperinflation often occurs when inspiratory efforts are initiated at a thoracic volume above the relaxation point of the respiratory system. The result is intrinsic positive end-expiratory alveolar pressure (PEEPi). To determine whether PEEPi occurs in ambulatory patients, we measured alveolar pressure (Palv) noninvasively during tidal breathing in 8 normal subjects, 15 asthmatic subjects, and 19 patients with COPD, using a body plethysmographic technique that includes computerized corrections for nonlinear pneumotachometer output and for plethysmograph leakage. In all 8 normal subjects, 9 asthmatic subjects, and 3 COPD patients, Palv descended smoothly to zero at end expiration. In contrast, among each of the remaining 22 patients, there was an abrupt change in slope of the Palv tracing near end expiration, identifying the onset of the next inspiratory effort and indicating the presence of PEEPi, ranging from 0.2 to 9.5 cm H2O. PEEPi was significantly correlated with FRC (% of predicted); PEEPi = (0.040 x %FRC) - 3.65, r = 0.73, p < 0.001, and with the reciprocal of FEV1 (% of predicted), PEEPi = (138/%FEV1) - 1.34, r = 0.69, p < 0.001. PEEPi could be elicited in normal subjects by severe expiratory resistive loading but not by the increased expiratory muscle activity occurring during an MVV maneuver. We conclude that PEEPi is common in patients with airways obstruction, even without overt ventilatory failure, and that its severity is generally in proportion to the severity of the hyperinflation and the airways obstruction. PMID- 8466119 TI - Assessment of diaphragm function using mouth pressure twitches in chronic obstructive pulmonary disease patients. AB - The relative invasiveness of the balloon catheter technique in measuring twitch transdiaphragmatic pressure (Pdit) limits its clinical use. By phrenic stimulation we obtained swings in mouth pressure (Pmt) in six COPD patients (age 50 to 72, FEV1 18 to 48% of predicted) at relaxed FRC (rFRC) and during graded inspiratory efforts (IE; twitch occlusion, TO). At rFRC, Pmt was damped and time lagged relative to the esophageal pressure twitch (Pes(t)), as if pressure had equilibrated through an RC system. Pmt was not correlated with Pdit. Conversely, Pmt and Pes(t) were always well matched during IE [Pmt = 0.971 (SEM +/- 0.028) Pes(t), r > 0.89], possibly in relation to a decrease in upper airway compliance or more uniform pleural pressure swings. Pmt decreased with the level of voluntary diaphragmatic contraction (Pdivol) in proportion to Pdit, reflecting a progressive increase in the level of diaphragm activation. During IE, Pmt was closely related to the voluntary mouth pressure in five subjects but not in the remaining subject, indicating intersubject variability in the level of diaphragmatic recruitment relative to other inspiratory muscles. We submit that measuring Pm during inspiratory efforts upon which bilateral phrenic stimulation is superimposed offers a relatively simple method for the assessment of diaphragm activation, potentially applicable in the clinical field. PMID- 8466120 TI - Effect of pressure and timing of contraction on human rib cage muscle fatigue. AB - Breathing against inspiratory loads can be accomplished with different degrees of coupling between the diaphragm and the other muscles attached to the rib cage (RCM). Thus, the electromyographic signs of fatigue develop separately in each muscle group. While breathing with diaphragm emphasis, the occurrence of diaphragmatic fatigue was found to be related to the tension-time index TTdi (= Pdi/Pdimax x Ti/Ttot). Above the critical range of 0.15 to 0.18, the endurance of the diaphragm is less than 1 h and it is inversely related to the TTdi value. However, in most loaded breathing conditions, the spontaneous pattern of breathing is characterized by predominant activation of RCM. The tension-time conditions at which fatigue develops during breathing with RCM emphasis are not known. We assessed the critical tension-time value in four normal subjects breathing with RCM emphasis against inspiratory threshold loads. RCM predominance was achieved by developing negative abdominal pressure swings during inspiration, and it was characterized by the tension-time index TTrc (Ppl/Pplmax x Tl/Ttot), where Ppl is pleural pressure developed under this condition. Above a critical TTrc value of 0.30, endurance time was inversely related to TTrc, and it resulted from failure of the RCM rather than of the diaphragm. We conclude that the critical threshold, as assessed by TTrc, is higher for breathing patterns with RCM emphasis than previously described by TTdi for diaphragm emphasis. However, when predominantly recruited, as in breathing patterns commonly adopted in loaded conditions, the RCM fatigue earlier than the diaphragm. PMID- 8466121 TI - Respiratory and peripheral muscle function in cystic fibrosis. AB - Respiratory muscle strength (RMS) and endurance are often preserved in cystic fibrosis (CF) despite malnutrition, chronic airflow limitation, and hyperinflation. Inspiratory muscle function may be relatively preserved due to a selective "training stimulus" from chronic lung disease. Respiratory and peripheral muscle function were evaluated in 14 stable CF patients and 16 healthy control subjects. RMS was measured using static maximal pressures performed at FRC. Respiratory fatigue (RF) was assessed using 18 repeated static efforts (10 s on/5 s off) over 4.5 min. Peripheral function was evaluated by leg strength (LS) and leg fatigue (LF) measured during sprint efforts on an isokinetic cycle ergometer. Despite a lower weight (mean +/- SD, 94 +/- 9.6% ideal wt for CF patients versus 107 +/- 14.6% for controls) and elevated residual volume (RV)/TLC ratio (38 +/- 13.0 versus 22 +/- 5.3), the CF group maintained RMS (inspiratory 96 +/- 23.2 versus 114 +/- 33.2; expiratory 105 +/- 28.3 versus 123 +/- 40.9 cm H2O) but had decreased LS (590 +/- 201.7 versus 813 +/- 167.1 W). There were no differences between the groups with respect to RF or LF. For the control group, inspiratory and expiratory RMS correlated with LS (p < 0.01) and lean body mass (p < 0.01). For the CF group, while expiratory RMS (p < 0.05) and LS (p < 0.01) correlated with lean body mass and each other (p < 0.01), inspiratory RMS was independent of lean body mass and LS (p > 0.1). Female CF patients appeared to have a better preservation of inspiratory RMS than males with CF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466122 TI - Maximum voluntary ventilation. Spirometric determinants in chronic obstructive pulmonary disease patients and normal subjects. AB - The 12-s maximum voluntary ventilation (MVV) provides an estimate of the ventilatory reserves available to meet the physiologic demands of exercise. Earlier studies established a general relationship between MVV and FEV1. We hypothesized that the resting maximum inspiratory flow rate (MIFR) also serves as a clinically useful predictor of the MVV. A total of 105 subjects, 45 women and 60 men (age 57 +/- 5 yr, mean +/- SD), with expiratory impairment categories of severe (n = 26), moderate (n = 22), mild (n = 18), and normal (n = 39) based on FEV1 (percentage of predicted), comprised the study samples. The ratio MVV/FEV1 averaged 41 +/- 7 overall. The FEV1 correlated with MVV in normal subjects (p < 0.05, r2 = 0.642) and patients (p < 0.05, r2 = 0.787) better than MIFR (p < 0.05, r2 > or = 0.480). MIFR joined with FEV1 in multiple linear regression to significantly improve the description of MVV:MVV L/min = 30.77FEV1 (L) + 5.94MIFR (L/s) - 4.77 (n = 105; p < 0.05, r2 = 0.849). The 95% confidence limits for MVV varied from 90 to 110% of predicted from the equation for this sample. The factors sex and impairment category did not reduce the unexplained variability in MVV after inclusion of FEV1 and MIFR as covariates in ANOVA (p > 0.05). Addition of MIFR to the model with FEV1 produced greater improvement in r2 than PImax. We conclude that MIFR, although secondary in importance to FEV1, is a significant determinant of MVV in patients with COPD and normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466123 TI - Theophylline delays skeletal muscle fatigue during progressive exercise. AB - In this study, 31P nuclear magnetic resonance spectroscopy (NMRS) was used to examine the effect of theophylline on human forearm muscle metabolism during progressive exercise. Six healthy men (37 +/- 14 yr of age) were assigned to either a control (CTRL) group (n = 3), or a theophylline treatment (THEO) group (n = 3). Each subject performed two dynamic wrist flexion exercise tests to fatigue, with at least 72 h separating each trial. The THEO group repeated the protocol after receiving 300 mg of sustained-release theophylline every 12 h. 31P spectra were acquired every 36 s throughout exercise, and the relative contributions of the phosphate metabolites and pH were determined. Power output at the onset, or threshold of intracellular acidosis (IT), was identified for each subject from changes in phosphocreatine (PCr) metabolism and pH. Power at maximal exercise and at the IT was found to be reproducible in the CTRL group. After theophylline administration, the maximal power attained by the THEO group increased significantly by 19% (p < 0.05), from 2.25 +/- 0.2 to 2.68 +/- 0.15 W. A similar trend occurred in the onset of the IT, which was also prolonged by 19%, from 1.33 +/- 0.18 to 1.58 +/- 0.22 W. Therapeutic concentrations of theophylline significantly increased the endurance of the forearm musculature, apparently by delaying the onset of intracellular metabolic acidosis. These findings suggest an enhancement of oxidative capacity of the muscle. PMID- 8466124 TI - Influence of non-REM sleep on inspiratory muscle activity and lung volume in asthmatic patients. AB - To determine the effect of non-REM (NREM) sleep on inspiratory muscle electromyographic (EMG) activity in asthmatic patients and the subsequent effect of such changes on FRC, 12 asthmatic patients with nocturnal worsening were monitored overnight in a horizontal volume-displacement body plethysmograph. During studies FRC was monitored using the single inspiratory occlusion technique, whereas EMG activities of the diaphragm (DI), intercostal (IC), and sternocleidomastoid (SCM) muscles were monitored using surface electrodes. FRC decreased progressively, from 3.63 +/- 0.27 L while awake prior to "lights out" to 3.15 +/- 0.27 L after 60 min of NREM sleep (p < 0.005). With awakening at the end of the study FRC increased to 4.69 +/- 0.48 L (p < 0.01). Onset of NREM sleep was also associated with significant (p < 0.05) reductions in EMG tonic activities of all three inspiratory muscles. These levels of tonic activity returned and were further augmented (p < 0.001) with awakening at the conclusion of the study. Linear relationships were demonstrated between sleep-state dependent changes in FRC and EMG tonic activity for each of the three inspiratory muscles (r = 0.98, 0.93, and 0.97 for DI, IC, and SCM, respectively, p < 0.01). NREM sleep did not significantly alter mean inspiratory phasic activities of these muscles, although there was considerable heterogeneity between individual subjects in the effects of NREM sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466125 TI - Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. AB - Obstruction of the upper airway during sleep (OSAS) is widely treated by having patients self-administer nasal continuous positive airway pressure (CPAP). To obtain objective evidence of the patterns of CPAP use, information was gathered from two urban sites on 35 OSAS patients who were prescribed CPAP for a total of 3,743 days. Patients were given CPAP machines that contained a microprocessor and monitor that measured actual pressure at the mask for every minute of each 24-h day for an average of 106 days per patient. They were not aware of the monitor inside the CPAP machines. Monitor output was compared with patients' diagnostic status, pretreatment clinical and demographic characteristics, and follow-up self reports of CPAP use, problems, side effects, and aspects of daytime fatigue and sleepiness. Patients attempted to use CPAP an average of 66 +/- 37% of the days monitored. When CPAP was used, the mean duration of use was 4.88 +/- 1.97 h. However, patients' reports of the duration of CPAP use overestimated actual use by 69 +/- 110 min (p < 0.002). Both frequency and duration of CPAP use in the first month reliably predicted use in the third month (p < 0.0001). Although the majority (60%) of patients claimed to use CPAP nightly, only 16 of 35 (46%) met criteria for regular use, defined by at least 4 h of CPAP administered on 70% of the days monitored. Relative to less regular users, these 16 patients had more years of education (p = 0.05), and were more likely to work in professional occupations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466127 TI - Do nasal ciliary changes reflect bronchial changes? An ultrastructural study. AB - Ciliary dyskinesia is characterized by recurrent respiratory tract infections secondary to abnormal ciliary structure and function. The diagnosis of ciliary dyskinesia is based on the detection of axonemal ultrastructural abnormalities (AUA) is respiratory mucosa samples. In most cases, the diagnosis of AUA is made on samples obtained from nasal ciliated cells with little discomfort to the patient. However, no studies have been performed in the same patient to confirm whether nasal samples reflect bronchial ciliary changes. To answer this question and to determine whether it is necessary to sample bronchial cells for the diagnosis of ciliary dyskinesia, we investigated 12 patients (between the age of 5 and 63 yr) with chronic sputum production. The presence of situs inversus, bronchiectasis, chronic sinusitis, and sterility was investigated to determine an inherited disorder. Two groups were established: Group 1 = six patients with an inherited disorder and Group 2 = six patients without evidence of an inherited disorder. Samples were obtained by brushing or biopsy of nasal and bronchial mucosa and were processed for transmission electron microscopy. In Group 1, the mean AUA was 65.2 +/- 11.4%. The following predominant axonemal defects were found: absence of dynein arms (DA) (four patients), central complex abnormalities (CC) (one patient), and various AUA (one patient). Nasal and bronchial samples correlated significantly for total AUA (r' = 1, p < 0.01) and for outer DA defects (r' = 0.96, p < 0.05). A good but not significant correlation was found for inner DA (r' = 0.83) and peripheral microtubule (PM) defects (r' = 0.71). In Group 2, the mean AUA was 9.6 +/- 2.3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466126 TI - IL-5 is the predominant eosinophil-active cytokine in the antigen-induced pulmonary late-phase reaction. AB - The mechanism of airway eosinophilia during antigen-induced inflammation was investigated by measurement of eosinophil-active cytokines utilizing an eosinophil survival assay. In the first study, 4 patients with allergic rhinitis underwent segmental bronchoprovocation (SBP) with low, medium, and high doses of ragweed extract instilled into different bronchial subsegments; bronchoalveolar lavage (BAL) fluids were collected from each segment 12 min and 48 h after challenge. Eosinophil granule proteins and eosinophil survival activity were significantly elevated in the 48-h (late-phase) BAL fluids from these segments. Correlations were observed between the concentrations of eosinophil granule proteins and eosinophil survival activity (rs = 0.717 to 0.880, p < 0.001) in BAL fluids. Eosinophil survival activity was completely neutralized by anti-IL-5 monoclonal antibody in five of the seven 48-h samples tested representing three of the 4 patients. In the two remaining samples, eosinophil survival activity was only partially neutralized by either anti-IL-5 antibody or anti-granulocyte macrophage colony-stimulating factor (GM-CSF) but was completely neutralized by anti-IL-5 and anti-GM-CSF in combination. Subsequently, in the second study, 10 patients with allergic rhinitis were challenged by SBP with ragweed extract. Eosinophil survival activity was significantly elevated in the 48-h BAL fluids; this activity was partially neutralized by anti-IL-5 antibody about (48%) and completely neutralized by the combination of anti-IL-5 and anti-GM-CSF antibodies. These findings suggest that the eosinophil survival activity in the late inflammatory lesions following SBP with allergen is mainly associated with IL-5, with small contributions from GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466128 TI - Pressure and flow changes in the pulmonary circulation in exercising sheep: evidence for elevated microvascular pressure. AB - The purpose of this study was to measure hemodynamic and transvascular filtration changes in the lung during strenuous exercise in sheep. The specific goals were (1) to determine the nature of the reduction in pulmonary arterial pressure (Ppa) after its initial peak rise with onset of exercise; (2) to use a pulmonary artery catheter distal wedge technique ("microwedge") to better assess longitudinal changes in resistance in the pulmonary circulation with exercise; and (3) to compare lung lymph flow and protein concentration changes at comparable estimated microvascular pressure (Pmv) (mean Ppa - mean left atrial pressure) (Pla) x 0.4 + mean Pla) during exercise versus passive left atrial hypertension to determine whether exercise causes a higher than expected lymph flow. We found that cardiac output rises quickly and thereafter remains constant with constant-rate exercise, and, thus, the secondary reduction in Ppa was due to vasodilation and/or recruitment. The microwedge pressure rose more than did Pla, suggesting that actual Pmv was probably higher than that estimated. With hypoxia, most of the change in pulmonary vascular resistance was in upstream vessels (arteries and capillaries), as was most of the exercise-induced vasodilation. Lymph flow rose more quickly and was much higher during brief exercise than during left atrial hypertension at a comparable calculated Pmv, and lymph protein content decreased more quickly. The data point to a Pmv with strenuous exercise that is higher than expected. PMID- 8466129 TI - Pulmonary hypertensive response to rabbit blood components in goats: role of thromboxane. AB - Transfusion of small quantities of heterologous blood may cause severe pulmonary hypertensive response in certain species. To determine the responsible component in the donor blood and the main mediator, we studied the responses of goats to small quantities of rabbit blood components and observed the effects of several pharmacologic agents on these responses. In anesthetized goats, a bolus injection of 0.004 ml/kg rabbit blood caused the pulmonary arterial pressure to increase from 25.3 +/- 2.8 to 57.1 +/- 11.6 cm H2O within 45 to 90 s, and the aortic thromboxane concentration rose from 44 +/- 38 to 238 +/- 104 pg/ml. Pulmonary vascular resistance increased more than 4-fold, whereas systemic vascular resistance increased moderately (50%). The erythrocyte stroma, mainly cell membranes, caused similar responses; other blood components were all ineffective. By blocking the production of thromboxane, indomethacin and U63557A (thromboxane synthetase inhibitor) abolished nearly all of the hemodynamic responses to rabbit blood. Isoproterenol also largely attenuated the responses to rabbit blood by blocking thromboxane production without interfering with the responses to the thromboxane mimic U46619. Nitrendipine (calcium-channel blocker) equally attenuated rabbit blood and U46619-induced hemodynamic responses but did not block thromboxane production. Chlorpheniramine (H1-receptor antagonist) partially blocked the hemodynamic responses to rabbit blood without affecting thromboxane production or U46619-induced responses. We conclude that the erythrocyte membrane is the responsible component in the donor blood and thromboxane is the predominant mediator. The main action of isoproterenol is to reduce thromboxane production and histamine participates by possible interaction with cyclooxygenase products. PMID- 8466130 TI - A study of monokine release and natural killer activity in the bronchoalveolar lavage of subjects with farmer's lung. AB - We examined the interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) releasability of alveolar macrophages and the natural killer (NK) cell activity in the bronchoalveolar lavage (BAL) cells of 11 patients with Farmer's lung at different stages of the disease. Although there were some variations in the levels of monokine release, macrophages of patients with acute disease secreted significantly higher spontaneous levels of TNF alpha than did a nonfarming control group (p = 0.0002). Conversely, TNF alpha release stimulated by bacterial lipopolysaccharide (LPS) was similar in patients with acute disease when compared with that in normal control subjects. IL-1 was also spontaneously secreted in significantly greater amounts by patients with acute Farmer's lung than by subjects in a control group (p = 0.0001). However, LPS-induced IL-1 release was significantly diminished in BAL macrophages from patients with acute manifestations of the disease when compared with that in control subjects (p = 0.001). Treating hypersensitivity pneumonitis with corticosteroids or by contact avoidance resulted in very significant decrease in spontaneous and LPS-stimulated IL-1 production by BAL macrophages (p = 0.0001 and p = 0.03, respectively), as well as in a decrease in spontaneous TNF alpha release that was also significant (p = 0.01). In addition, BAL cells of patients in the acute phase had a significant NK cell activity (mean +/- SEM of 18.33 +/- 2.65%). Treatment of these patients resulted in an increase in NK cell activity (mean of 40.17 +/- 7.86%), which was significantly different from values of patients with acute disease (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466131 TI - Clinical significance of borderline quantitative protected brush specimen culture results. AB - In patients with clinical suspicion of pneumonia, quantitative cultures of protected brushing specimens (PBS) yielding > or = 10(3) CFU/ml of at least one microorganism have been found useful for differentiating airway colonization and lung infection, especially in mechanically ventilated patients. The amount of secretions collected by protected catheter brushing is small and difficult to determine accurately. Thus, the clinical significance of PBS cultures yielding organisms in concentrations > or = 10(2) but < 10(3) CFU/ml, in the absence of active antimicrobial treatment, is unknown. The 34 consecutive results of PBS cultures yielding organisms in concentrations > or = 10(2) but < 10(3) CFU/ml in 30 patients under mechanical ventilation or weaned for < or = 4 days were prospectively studied. No patients were receiving agents active on the organism recovered. In 5 cases, the diagnosis of pneumonia was ruled out by recovery without treatment (n = 4) or negative postmortem lung cultures (n = 1). A second PBS was cultured in 29 episodes (2.7 +/- 1.8 days after the first PBS). In 12 instances (Group 1), cultures of the second PBS yielded > or = 10(3) CFU/ml of the same organism as that found in the first PBS (S. pneumoniae, 1; S. aureus, 1; H. influenzae, 1; E. coli, 1; P. aeruginosa, 4; and A. baumannii, 4), and these patients were therefore treated with appropriate antibiotics. A total of 17 patients had a negative repeat PBS culture (no growth or trivial concentrations) and were considered free of pneumonia and given no antibiotic treatment for this episode.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466132 TI - Specificity of endotracheal aspiration, protected specimen brush, and bronchoalveolar lavage in mechanically ventilated patients. AB - The specificity of the different techniques used to diagnose ventilator associated pneumonia is still a matter of controversy. To investigate the specificity of endotracheal aspiration (EA), protected specimen brush (PSB), and bronchoalveolar lavage (BAL) quantitative cultures, we studied 27 consecutive mechanically ventilated (MV) patients (> 72 h) without clinical or radiographic evidence of pulmonary infection. Comparing different thresholds for quantitative cultures (from 10(3) through 10(6) CFU/ml), the lowest rate of false positive results was obtained using 10(6) for EA, 10(5) for PSB, and 10(6) for BAL. Using 10(6) CFU/ml for EA, 10(4) CFU/ml for PSB, and 10(5) CFU/ml for BAL as cutoff points, we obtained the following specificities: 85, 85, and 78% for the three techniques, respectively. A bacterial index of 8 was the best threshold to get a low percentage of false positive results for all techniques except for EA (0% for PSB and 12% for BAL). There were reasonable qualitative agreements (PSB versus EA = 58%; BAL versus EA = 69%; and PSB versus BAL = 62%) and poor quantitative correlations between concomitantly isolated microorganisms from the three types of samples. Quantitative cultures of EA, PSB, and BAL may show a considerable percentage of false positive results at the respective cutoff points usually accepted. Increasing the thresholds for quantitative cultures, albeit loosing sensitivity, may rule out better the absence of pulmonary infection in MV patients. PMID- 8466133 TI - Quantitative bacillary response to treatment in HIV-associated pulmonary tuberculosis. AB - A group of 122 patients with culture-proven pulmonary tuberculosis were recruited to examine the concentrations of Mycobacterium tuberculosis in sputum and the relationship to HIV-1 antibody status. They were followed for up to 28 days from the start of antituberculous chemotherapy to assess the early bacillary response to two chemotherapeutic regimens. Of 67 treated with streptomycin, thiacetazone, and isoniazid 17 were HIV positive, and subsequently 55, of whom 20 were HIV positive, were treated with streptomycin, rifampin, isoniazid, and pyrazinamide. The mean initial concentration of M. tuberculosis in the sputum of the HIV negative patients was significantly higher than in HIV-positive patients (6.95 and 6.34 log colony-forming units respectively; p = 0.019). The HIV-positive patients had less radiologic evidence of disease and significantly fewer zones of lung affected with cavities. The response to treatment was similar, but with HIV positive patients more likely to become culture negative by 28 days. The differences that exist between HIV-positive and HIV-negative patients are minor, and standard regimens are at least as effective in HIV-positive patients in the first month of treatment. PMID- 8466134 TI - Intrapleural streptokinase in experimental empyema. AB - Intrapleural streptokinase has been used in multiloculated empyemas to enhance pleural space drainage, presumably by causing fibrinolysis of the interlocular septae. We evaluated the efficacy and safety of daily administration of 10,000 U intrapleural streptokinase or equal volumes of saline to enhance resolution of experimental empyema in the rabbit pleural space. Seventy-two hours after intrapleural turpentine, 10(8) colony-forming units each of Escherichia coli, Peptostreptococcus anaerobius, and Bacteroides fragilis were injected into the sterile pleural effusion of all animals. Immediately after bacterial inoculation, and daily for 3 days, animals received 10,000 U streptokinase or saline intrapleurally. Animals that achieved a pleural fluid pH < 7.30 and either glucose < 50 mg/dl or LDH > 500 IU/L were included for data analysis. At Day 4 after bacterial inoculation, the streptokinase-treated empyemic rabbits had more pleural fluid (18.8 +/- 5.1 ml) (mean +/- SEM) than did saline-treated control animals (4.8 +/- 1.7 ml) (p = 0.015), fewer interpleural adhesions (8.2 +/- 2.7) than did saline-treated control animals (25.1 +/- 3.6) (p = 0.002), and comparable amounts of visceral and parietal pleural plaque than did saline treated control animals (p = NS). No evidence of systemic fibrinolysis was observed at 1 h after intrapleural streptokinase administration. We conclude that intrapleural streptokinase decreases interpleural adhesion numbers but fails to reduce the amount of pleural plaque observed in experimental empyema in rabbits. The increases in pleural fluid volume observed after streptokinase administration may be due to mechanisms other than fibrinolytic activity. PMID- 8466135 TI - Inflammatory cell populations in the airways and parenchyma after antigen challenge in the rat. AB - We examined the effects of sensitization and antigen challenge on the cellular populations retrieved from the large airways (LA) (generations zero to 5 approximately) and small airways and parenchyma (S/P) of the rat. Male Brown Norway rats, 7 to 8 wk of age, were either actively sensitized to ovalbumin (n = 24) or sham-sensitized to saline (n = 9), and, 14 days later, they were anesthetized with urethane, intubated endotracheally, and challenged. Aerosols of ovalbumin (5% wt/vol in saline for 5 min) or saline were administered to 12 and six rats, respectively, and measurements of pulmonary resistance (RL) were made for 8 h. The early airway response (ER) was calculated as the highest value of RL in the first hour after challenge, and the late response (LR) was calculated as an increase in RL to greater than 200% of the baseline value in the 4- to 8-h period after challenge. Rats were killed by exsanguination, LA were separated from S/P, and cells were isolated after tissue mincing and digestion with collagenase. Total and differential cell counts and lymphocyte subsets were determined. Antigen challenge significantly increased the cellular yield (mostly neutrophils) from the LA and S/P. Animals with a LR had a lower total cellular yield from the LA and S/P than did animals without a LR. The animals with a LR also had a lower yield of eosinophils and lymphocytes from the S/P than did animals challenged with saline alone. Cellular yields were not lower in the animals with an isolated ER after antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466136 TI - Collagen and elastin in human pulmonary emphysema. AB - Studies of collagen and elastin in pulmonary emphysema have been controversial. The problems involve methodologic differences; often whole lungs have been sampled and the types of emphysema have not been classified. Quantification of collagen and elastin is important since the increase in collagen supports the inflammatory-repair hypothesis of emphysema, which has been recently revived. On the other hand, loss of elastin supports the protease-antiprotease hypothesis. Accordingly, we measured collagen (hydroxy-proline) and elastin (desmosine) in 147 small samples of human lungs removed for cancer. The amount and type of collagen were also assessed histochemically in tissue blocks adjacent to the tissue used for the biochemical analysis. We found that collagen in the homogenates was increased only in irregular airspace enlargement, but histochemically, collagen was consistently increased in centriacinar, distal acinar, and irregular air-space enlargement sections. Elastin was decreased in all grades of panacinar air-space enlargement and also in severe centriacinar air space enlargement. Our data support both the protease-antiprotease imbalance hypothesis in panacinar and the inflammatory-repair hypothesis in centriacinar, distal acinar, and irregular air-space enlargement. PMID- 8466137 TI - The effect of human eosinophil granule major basic protein on airway responsiveness in the rat in vivo. A comparison with polycations. AB - Major basic protein (MBP) is a highly cationic protein found in the granules of eosinophils. It has been postulated that MBP may participate in the pathogenesis of airway hyperresponsiveness exhibited by asthmatic patients. Accordingly, we used a rat model to investigate the effect of human MBP instillation on airway responsiveness and the possible role of cationic charge in the determination of this effect. Dose-response characteristics to inhaled methacholine (MDRC) were determined at baseline, and the animals were allowed to recover. Then animals in the experimental group received 100 micrograms of purified human MBP via direct instillation into the trachea. One hour after instillation, the MDRC were again assessed. Control animals received (in lieu of MBP) buffer from the void volume pool of the same chromatography column used to purify the MBP. One hour after instillation of MBP there was a significant increase in airway responsiveness to inhaled methacholine, whereas control animals exhibited no increase in airway responsiveness. Some animals from the MBP group were restudied 48 h after MBP instillation, by which time airway responsiveness had returned to baseline level. The effect of the polycations poly-L-arginine and poly-L-lysine on airway responsiveness was also examined. As with MBP, airway responsiveness to inhaled methacholine increased 1 h after the instillation of either polycation. In addition, acetylation of the charged groups on poly-L-lysine resulted in a loss of this effect. Histologic examination of the airways failed to reveal airway epithelial shedding 1 h after MBP or polycation instillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466138 TI - Experimental hydrostatic pulmonary edema in rabbit lungs. Morphology. AB - To study the accumulation and distribution of edema fluid and the associated changes in alveolar microarchitecture, edema was induced in excised rabbit lungs perfused with 6% albumin solution. The lungs, including the edema fluid, were then fixed by vascular perfusion with glutaraldehyde, osmium tetroxide, and uranyl acetate. Tissue samples were analyzed by light microscopy and transmission and scanning electron microscopy. We found (1) fixation was successful in that the albumin in the edema fluid formed coherent webs indicating the location and arrangement of the extravascular fluid accumulations; (2) regardless of the filtration pressure (about 29 mm Hg in one set of experiments and about 14 mm Hg in the other), an apical to basal gradient of fluid accumulation was found. This gradient was absent in lungs held in the inverse position, suggesting that the regional distribution of pulmonary edema is not simply gravity dependent. At the same lung height, there was a remarkable inhomogeneity of interstitial and alveolar edema. (3) Both the inhomogeneous distribution of fluid and the resulting changes in surface tension affected the entire alveolar architecture. (4) Within interstitial and alveolar spaces, there were striking inequalities in the density of the proteinaceous fluid pools that suggest local differences in the sieving properties of the barriers, that is, in the reflection coefficients for albumin. In conclusion, our findings suggest that the formation of pulmonary edema cannot be explained solely by uniform membrane models for fluid exchange. PMID- 8466139 TI - Experimental hydrostatic pulmonary edema in rabbit lungs. Barrier lesions. AB - In excised rabbit lungs perfused with a 6% albumin solution, hydrostatic pulmonary edema was induced by moderate (about 14 mm Hg) and high increases (about 29 mm Hg) of capillary transmural pressure. Thereafter, lung tissue and proteinaceous edema fluid were fixed by vascular perfusion and analyzed by electron microscopy for possible lesions of the blood-gas barrier. The following observations appear noteworthy: (1) There were distinct and numerous lesions of the epithelial cell layer. In high-pressure edema, frank disruptions on the thin and thick sides of the blood-gas barrier were prominent. In moderate pressure edema epithelial blebs were more conspicuous. (2) In contrast, endothelial lesions were rare in both high- and moderate-pressure experiments. (3) Epithelial Type I cells revealed an enormous plasticity as illustrated by the formation of large epithelial blebs. (4) Although the entire microvasculature was subjected to high pressures, barrier lesions were exclusively seen in regions with alveolar edema. These findings suggest that barrier leaks play a role in both hydrostatic and permeability lung edema and that the differences between both types of edema rather reflects the type and extent of injury to the alveolar epithelial barrier and the associated inflammatory reaction. PMID- 8466140 TI - The role of clinical biochemistry departments in developing a research infrastructure. PMID- 8466141 TI - Would DNA repair assessment benefit patient management? PMID- 8466142 TI - Laboratory diagnosis of phaeochromocytoma: which analytes should we measure? AB - There is a diversity of advice in the literature as to which biochemical assays are best suited to the investigation of patients with a suspected phaeochromocytoma. The challenge for the clinical laboratory is to select those assays which detect all phaeochromocytomas, whilst having the lowest incidence of false positive diagnoses. We compared the sensitivity and specificity of a wide range of assays currently used for the biochemical diagnosis of phaeochromocytoma using either specific gas chromatographic-mass spectrometric (GC/MS) or high performance liquid chromatography-electrochemical detection (HPLC/ED) techniques. Noradrenaline (NA), adrenaline (ADR), dopamine (DA), 3,4-dihydroxyphenylglycol (DHPG), hydroxymethoxymandelic acid (HMMA), normetanephrine (NMET) and metanephrine (MET) were measured in 24 h urine specimens from 20 patients with histologically proven phaeochromocytoma and a large group of patients referred for investigation but subsequently found not to have a phaeochromocytoma. Because phaeochromocytomas are a heterogeneous group of hormone secreting tumours, no single analyte could achieve 100% sensitivity; 100% sensitivity was achieved only when the combination of both NA and ADR or NMET and MET was used. DA, DHPG and HMMA all had poor sensitivities. HMMA had a sensitivity of 70% when using the upper 95% confidence level (48 mumol/24 h) of the non-tumour patients as the cut off. By lowering the cut-off to 35 mumol/24 h the sensitivity could be increased to 100% but at the expense of the specificity which was decreased from 98 to 92%. On the basis of this study we recommend the specific measurement of either NA and ADR or NMET and MET as the most suitable analytes for the detection of phaeochromocytoma, and further that, due to its poor specificity, HMMA be abandoned as a suitable analyte. PMID- 8466143 TI - Estimation of sulphoconjugated catecholamine concentrations in plasma by high performance liquid chromatography. AB - Free and sulphoconjugated catecholamine (CA) concentrations were measured in plasma using a fully automated and sensitive analyser equipped with a three column system of high-performance liquid chromatography (HPLC). Although the free dopamine (DA) concentration has been below the detection limit of HPLC analysers thus far available, this new CA analyser can measure as little as 0.03 nmol/L. For the estimation of sulphoconjugated CA, we performed enzymatic deconjugation with arylsulphatase prior to HPLC analysis. The difference between free and total concentrations represents that of sulphoconjugated CA. The intraassay coefficient variation was less than 2.2% for free noradrenaline (NA) and adrenaline (A), 12.62% for free DA, and less than 4.3% for total A, and DA. These assays of free and sulphoconjugated CA are simple and can be performed routinely by a suitably equipped laboratory. PMID- 8466144 TI - Identification of sources of lead exposure among children in Arar, Saudi Arabia. AB - The concentrations of lead and the isotopic ratios of lead, 206Pb:207Pb, were measured by inductively coupled plasma-mass spectrometry in environmental specimens, cosmetics and traditional remedies. The ratios were compared with those found in blood samples of Saudi children who had increased concentrations of total blood lead. The isotopic ratios in the blood specimens (1.144 +/- 0.027) were not significantly different from those determined in cosmetics and remedies (1.152 +/- 0.031) and indicated that these were the likely sources of exposure rather than the lead contained in petrol which had an isotopic ratio of 1.207. PMID- 8466145 TI - Predicting the probability of helper T cell immunodominant sites through discriminant analysis. AB - Bayesian discriminant analysis is used to predict whether or not a given protein segment will activate helper T cells. The predictor variables are drawn from the products of frequencies of amino acid residues. The model's predictive validity compares favourably with that of alternative modelling strategies, suggesting that this approach merits further investigation. PMID- 8466146 TI - Analysis of apolipoprotein size distribution by electroimmunoblotting from non denaturing composite gels. AB - An exponential gradient gel with 0-35% acrylamide and 0.5% agarose was developed for electrophoresis of intact lipoproteins with subsequent electroimmunoblotting. The system resolved in a single gel lipoprotein-associated proteins of sizes from 'free' apoproteins to VLDL. Reproducibility between gels was good (coefficient of variation < 8%). Examination of the effect of mild glutaraldehyde fixation on immunodetection showed variable results (lack of effect on apos (a), AII, and AIV; inhibition of apoB; enhancement of apos AI and E). The composite gel system described here will simplify analysis of apolipoprotein distributions in both health and disease and therefore will likely be useful in future clinical applications. PMID- 8466147 TI - An evaluation of the measurement of drugs of abuse by commercial and in-house horizontal thin layer chromatography. AB - We have compared an in-house horizontal thin layer chromatography (TLC) method with a commercial TLC screening kit (Toxi-Lab) to find the most suitable method for screening urine for opioid drugs. The in-house TLC procedure is cheaper and more efficient than the commercial TLC method and is ideal as a confirmatory method when used in conjunction with other established laboratory methods. The in house TLC method is useful for one-off requests and is able to differentiate between small quantities (0.1-0.5 mg/L) of the different, commonly abused opioids and their metabolites, which means that it is well suited for use at a local Drug Addiction Unit as a routine screening service. PMID- 8466148 TI - Glycohaemoglobin: comparison of 12 analytical methods, applied to lyophilized haemolysates by 101 laboratories in an external quality assurance programme. AB - Stable lyophilized ethylenediaminetetra-acetic acid (EDTA)-blood haemolysates were applied in an external quality assurance programme (SKZL, The Netherlands) for glycohaemoglobin assays in 101 laboratories using 12 methods. The mean intralaboratory day-to-day coefficient of variation (CV), calculated from the assay of 12 unidentified pairs over a period of 1 year, was 5.2% (range: 0.2 28.7). Forty-seven per cent of laboratories did not meet the criterion of CV < 5%, whereas 68% did not meet the clinically more desirable 3.3-3.6%. Linearity, as derived from the analysis of five combinations of two haemolysates with low and high glycohaemoglobin percentages over 6 months, was excellent (mean correlation coefficient 0.9953; range: 0.9188-0.9999). Analysis of two samples with high and low glycohaemoglobin percentages gave mean interlaboratory coefficients of variation of 10% for one method performed by several laboratories and 22% for all methods performed by all laboratories. It is concluded that the majority of laboratories do not meet the clinically desirable intralaboratory precision and that an unacceptably high interlaboratory precision exists. PMID- 8466149 TI - A robust procedure for the automated measurement of total serum bilirubin using potassium ferricyanide. AB - Bilirubin is oxidized to biliverdin by 1.0 mmol/L potassium ferricyanide in the presence of caffeine. The absorbance decline at 480 nm with blanking at 660 nm is proportional to bilirubin concentration. The assay is linear up to 1000 mumol/L and is suitable for the measurement of bilirubin in adult and neonatal patients. The assay is accurate and precise and is not significantly affected by haemolysis up to 5.0 g/L haemoglobin. Reagents and calibration are stable for at least 3 months. PMID- 8466150 TI - Urinary growth hormone excretion as measured by a sensitive immunochemiluminometric assay. AB - A sensitive immunochemiluminometric assay with a detection limit of 1.1 microU/L was developed for the measurement of urinary growth hormone (UGH). The assay was shown to be specific and precise. There was a good correlation between serum growth hormone (GH) and UGH concentrations in 20 patients with acromegaly and six volunteers following an intravenous injection of recombinant GH. We concluded therefore that UGH measurements appear to provide a satisfactory index of GH secretion. The use of the assay in the investigation of growth disorders was assessed. We studied 11 pre-pubertal children, six of normal stature, and five of short stature, over a 6-month period. Sequential fortnightly measurements of UGH were carried out and height velocity was determined. The children of short stature grew at a slower rate and excreted less GH than the children of normal stature. However, we observed considerable within-individual variability in GH excretion in both groups (CV 22-98%). We therefore recommend that sequential UGH analyses should be carried out and the results interpreted in conjunction with growth measurements. However, further investigations into the renal handling of GH are needed to establish optimum sampling regimes. PMID- 8466151 TI - Comparison of a commercial enzymic kit for urinary oxalate analysis with a high performance liquid chromatographic method. AB - A new commercial enzymic kit for urinary oxalate determination has been adapted for use on a centrifugal analyser. It has been evaluated and compared with an established high performance liquid chromatographic (HPLC) procedure developed in our laboratory. Mean recovery of oxalate from urine samples augmented with oxalic acid exceeded 97% by both methods. The precision of the HPLC method was superior to that of the enzymic kit but both methods gave between batch precision values better than CV 12% at low (less than 100 mumol/L) oxalate concentrations and better than CV 7% at higher concentrations (greater than 270 mumol/L). Urinary oxalate values obtained with the new enzymic procedure correlated more closely with HPLC values (r = 0.84) than did values previously obtained using the forerunner of the kit (r = 0.62) which was known to be susceptible to ascorbate interference. No significant interference from ascorbic acid or from high urinary calcium concentrations could be demonstrated using either the improved kit or the HPLC procedure. Its easy adaptation to automated analysers available in most laboratories, coupled to its acceptable analytical performance render the enzymic kit a reasonable alternative to HPLC or other more complex procedures for urinary oxalate analysis. PMID- 8466152 TI - Bone-derived serum enzymes and bone density in perimenopausal Caucasian women. AB - Serum levels of bone-origin alkaline phosphatase and of tartrate-resistant acid phosphatase were measured in Caucasian women aged 41-69 years who had volunteered for bone densitometry. Bone alkaline phosphatase and tartrate-resistant acid phosphatase were inversely correlated with vertebral bone density and with femoral neck bone density. Bone alkaline phosphatase and acid phosphatase were also significantly correlated, consistent with the concept of 'coupling' between osteoblast and osteoclast activity. PMID- 8466153 TI - Insulin and proinsulin-like molecules in motor neurone disease. PMID- 8466154 TI - Serum glycated albumin concentrations during pregnancy. PMID- 8466155 TI - Thin layer chromatographic identification of thromboxane B2 in serum, and platelet rich plasma stimulated by arachidonic acid and collagen. PMID- 8466156 TI - Monitoring erythropoietin therapy for anaemia of chronic renal failure by serum erythropoietin assays. PMID- 8466157 TI - Alpha-fucosidase as a marker of genetic deletion in ovarian carcinoma. PMID- 8466158 TI - A simple method for measuring neopterin in serum using HPLC. PMID- 8466159 TI - Keep the lid on it: artefactual hypernatraemia in samples from paediatric patients. PMID- 8466160 TI - Storage of plasma in primary plasma separator tubes. PMID- 8466161 TI - Inhibition of the urease reaction by boric acid. PMID- 8466162 TI - Hyponatraemia and hypouricaemia. PMID- 8466163 TI - Elevated levels of maternal serum inhibin immunoreactivity in second trimester pregnancies affected by Down's syndrome. PMID- 8466164 TI - Interaction between bovine control materials and the ferene iron method. PMID- 8466165 TI - Europium labelled time-resolved fluoroimmunoassay for urine albumin. PMID- 8466166 TI - Hyperammonaemia--an important cause of encephalopathy: three case reports. PMID- 8466167 TI - Seminal fluid contamination of urine. PMID- 8466168 TI - Cardiac action potentials, membrane currents, and some personal reminiscences. PMID- 8466169 TI - Aldosterone action. PMID- 8466170 TI - The insulin-like growth factors. AB - The recent availability of reagents to study the IGFs, their receptors, and binding proteins has led to an explosive growth in the study of IGF physiology. However, most studies to date have been descriptive, and studies delineating mechanisms of action are limited. It is apparent that most organ systems synthesize several components of the IGF system necessary for IGF to function in an autocrine or paracrine fashion and that regulation of this system occurs at the local level. However, the relative importance of locally produced IGF vs circulating IGF remains unclear. The mechanisms by which the IGFBPs modulate IGF activity are crucial to understanding this system, and identification of specific roles for each of these proteins will be required. Of critical importance is the identity of the intracellular signal transduction system by which the IGF receptor mediates the effects of the IGFs, and the delineation of mechanisms by which the IGFBPs interact with the receptor at the cellular level. It is also of interest to determine what role, if any, the IGF-II receptor plays in mediating the growth-promoting effects of the IGFs. The ubiquitous distribution of the IGFs, IGFBPs, and IGF receptors indicates that they may play a role in the regulation of coordinate growth among several tissues and cell types. Understanding the mechanisms by which these components interact to coordinate growth responses between different cell types should greatly enhance our understanding of normal growth and development. PMID- 8466171 TI - Mechanical factors in lung liquid distribution. PMID- 8466172 TI - Temporal organization: reflections of a Darwinian clock-watcher. PMID- 8466173 TI - Gene transfection of lung cells in vitro and in vivo. PMID- 8466175 TI - Neutrophil-endothelial cell interactions in the lung. AB - The large marginated pool of neutrophils normally present in the pulmonary circulation provides a unique opportunity to study the relationship between neutrophils and endothelial cells in situ. Unlike other organs in which neutrophil density in the vascular space is low, adequate numbers of cells are readily available in the lung to assess such important characteristics as distribution, density, size, volume, and immunocytochemical and cytochemical characteristics. To take advantage of such a large marginated pool, morphologic techniques should be more universally applied in studies of neutrophil-mediated tissue injury. From the data presented, it seems clear that factors governing neutrophil-endothelial cell interactions may differ in the lung compared to systemic vascular beds. We have suggested that this difference may be related to the unique characteristics of the lung with regard to anatomy and blood flow rather than site-specific differences in endothelial cells. With the discovery of specialized proteins involved in cell adhesion and the increasing availability of appropriate antibodies to adhesion proteins, unprecedented opportunities exist to address these questions. It is an exciting time to study neutrophil-endothelial cell interactions in the lung. PMID- 8466176 TI - Endothelin peptides and the kidney. PMID- 8466174 TI - Interrelationship of pleural and pulmonary interstitial liquid. AB - When the lung interstitium fills with liquid, lung interstitial liquid may flow across the visceral pleura into the pleural space. This route of interstitial liquid flow does not apparently depend on the type of edema because it is used equally in both hydrostatic and increased permeability edema. The route of flow depends mostly on the quantity and location of extravascular lung water. In experimental studies of hydrostatic and increased permeability edema, pleural effusion develops when extravascular lung water has reached a certain level for a certain amount of time. The necessary level of edema appears to be greater than 5.0 g/g dry lung, whether in hydrostatic edema [5.2-6.2 g/g dry lung (14); 5.0 6.5 g/g dry lung (4)] or in increased permeability edema due either to ANTU [5.1 9.3 g/g dry lung (45)], oleic-acid [6.5-8.0 g/g dry lung (58)], or alveolar P. aeruginosa [5.4-6.7 g/g dry lung (J. Wiener-Kronish, unpublished observations)]. The amount of lung edema necessary for pleural effusion formation is similar to the amount of edema Bhattacharya and co-workers found to be associated with the steep rise in subpleural pressure (7). The time before appearance of pleural effusion appears to be approximately 2 hr after the development of lung edema, whether the effusion results from hydrostatic edema (14) or increased permeability edema due to ANTU (48) or oleic acid (58). This delay may be necessary for the interstitial liquid to accumulate and the interstitial pressure to increase in the subpleural tissues to the point that liquid flows across the visceral pleura at a rate greater than the rate at which the parietal lymphatics can clear it. Consequences of a pleural route of edema clearance are several. Pleural effusion that develops in the course of lung edema represents lung interstitial edema and can be sampled in lieu of sampling lung lymph. Indeed, pleural liquid may be a better sample of lung interstitial liquid than is alveolar edema liquid. The flow of lung interstitial liquid to the pleural space can protect against the development of alveolar edema by transferring excess liquid from the lung interstitium to the pleural space, where the effects on lung function are relatively minor. Obliteration of the pleural space may either lower the threshold for development of alveolar edema in the adjacent lungs, or slow the clearance of established edema; with chronic edema, other routes of clearance would likely adapt to compensate for the loss of the pleural clearance route. PMID- 8466177 TI - Function and regulation of collecting duct intercalated cells. PMID- 8466179 TI - Synchronization of cortical activity and its putative role in information processing and learning. PMID- 8466178 TI - Role of growth factors in regulation of renal growth. AB - It is clear that a number of growth factors are synthesized within the adult and the developing kidney. Compelling evidence exists that several of these agents orchestrate the nephrogenic process. A growing body of data supports roles for one or more of these agents in the adult kidney as regulators of renal function, growth, and repair processes. Growth factor expression may be the cause of glomerulosclerosis in one or more pathophysiological states. Our knowledge of the sites of growth factor synthesis and actions in the kidney and of the mechanisms by which growth factor synthesis is regulated and actions are exerted is rudimentary. Expansion of this knowledge base is likely to result in a greater understanding of renal disease mechanisms and thereby generate strategies by which kidney damage can be halted, prevented, or reversed. PMID- 8466180 TI - The mechanism of expression of long-term enhancement of hippocampal synapses: current issues and theoretical implications. PMID- 8466181 TI - Structural changes accompanying memory storage. PMID- 8466182 TI - Comparative aspects of muscle capillary supply. PMID- 8466183 TI - Contraction dynamics and power output of skeletal muscle. PMID- 8466184 TI - Limits to maximal performance. AB - Body size fundamentally affects maximal locomotor performance in mammals. Comparisons of performances of different-sized animals yield different results if made using relative, rather than absolute scales. Absolute speed may be a reasonable way to evaluate the locomotor performance of an animal that must escape predators in real time. However, comparisons of metabolic power in animals of different size can only be made meaningfully on a mass-specific basis. Numerous factors associated with the mechanics, energetics, and storage of elastic energy during locomotion change with body size, which results in allometric relationships that make the energetic cost of locomotion (alpha Mb 0.3) more expensive for small mammals than for large mammals. Small mammals have lower enzymatic capacities for anaerobic glycolysis (alpha Mb0.15) and higher specific aerobic capacities (alpha Mb-0.13) than large mammals. However, the energetic cost of transport increases more than aerobic power as mammals get smaller. The higher ratio of cost to available power in small mammals may explain why they run more slowly than large mammals, as a rule. Maximum aerobic capacity is allometrically related to body size. Limits to VO2max can be imposed by mitochondrial oxidative capacity, as in goats, or by the O2 transport system, as in humans and horses. No single step in the O2 transport system can limit the flux of O2 by itself; however, in an average non-athletic species of mammal, any of the steps in the system might appear to be the weakest link. In highly aerobic athletic species, and possibly elite athletic individuals of other species (e.g. humans), the malleable elements of the O2 transport system may develop to the point that their O2 transport capacities approach that of the least malleable element in the system, the lung. VO2max is very high in such individuals, and appears to be limited by simultaneous failure of all components of the O2 transport system. PMID- 8466185 TI - Control of cardiac gene expression by mechanical stress. PMID- 8466186 TI - The intestinal Na+/glucose cotransporter. PMID- 8466187 TI - Facilitated glucose transporters in epithelial cells. AB - The molecular cloning of facilitated sugar transporters has led to the identification of a family of transport molecules having similar functions, but possessing specific kinetic and regulatory properties. These transporter isoforms are characterized by different primary structures, specific tissue localization, and polarized expression within the same epithelial cells. The use of Xenopus oocytes for the functional expression of different members of this transporter family has been of considerable value in defining the kinetic properties and sugar specificities of the different isoforms. The expression of chimeric or variously mutated transporters should, in the near future, permit the determination of the structural basis for their kinetic properties and sugar specificities. cDNA probes and antipeptide antibodies specific for each isoform are now being used to determine their specific regulation during development and in different states of altered glucose homeostasis. The variety of molecular forms implicated in the apparently simple task of sugar uptake or transepithelial transport has been surprising. With the available molecular tools now in hand, it will be possible to study these mechanisms in much greater detail. PMID- 8466188 TI - Formal approaches to understanding biological oscillators. AB - In this brief review, we have attempted to illustrate the utility of our qualitative scheme proposed in 1984 (27). This scheme provides a means of summarizing information concerning oscillating systems by identifying system variables and parameters and the interactions between variables. Moreover, the qualitative scheme can be employed to deduce the form of system differential equations. This second step then clearly shows the rate constants that must be deduced through experimentation for the construction of explicit mathematical models. PMID- 8466189 TI - Genetic analysis of circadian clocks. PMID- 8466190 TI - Molecular approaches to understanding circadian oscillations. PMID- 8466191 TI - Controlling cell chemistry with caged compounds. PMID- 8466192 TI - Transcriptional regulation during cardiac growth and development. PMID- 8466193 TI - Multimode light microscopy and the dynamics of molecules, cells, and tissues. PMID- 8466195 TI - AORN supports HIV testing, counseling. PMID- 8466194 TI - Transgenic mice in cardiovascular research. PMID- 8466196 TI - Let's put our fear of HIV in proper perspective. PMID- 8466197 TI - Anesthesia personnel. PMID- 8466198 TI - Sterile technique. PMID- 8466199 TI - Cervical spine injury. Perioperative patient care. PMID- 8466200 TI - Ultrasonic surgical aspiration. An expanding method for patient treatment. PMID- 8466201 TI - Perioperative nursing in Uganda. Improvisation, creativity. PMID- 8466202 TI - Assert yourself. Effective communication for nurses. PMID- 8466203 TI - Preoperative teaching strategy. Videotapes for home viewing. PMID- 8466204 TI - Employee recognition. A working model to enhance job satisfaction. PMID- 8466205 TI - The holding room. A preoperative advantage. PMID- 8466206 TI - Labor budgeting. Automating the manual system. PMID- 8466207 TI - Stressors of providing care to the elderly. PMID- 8466208 TI - Do-not-resuscitate orders in the operating room. AB - Surgery offers patients the chance to improve the quality and longevity of their lives, but surgery and anesthesia are not without risks. Patients should have the opportunity to make informed choices about the risks they take with respect to their health care. Perioperative nurses must be knowledgeable about advance directives and the implications they have for surgical care, and they must support patient autonomy by respecting the choices and decisions patients make about their care. PMID- 8466209 TI - Legal implications of perioperative documentation. PMID- 8466210 TI - Proposed recommended practices. Environmental responsibility in the practice setting. Association of Operating Room Nurses. PMID- 8466211 TI - Recommended practices. Monitoring the patient receiving i.v. conscious sedation. Association of Operating Room Nurses. PMID- 8466212 TI - A pilot study of iontophoretic cisplatin chemotherapy of basal and squamous cell carcinomas of the skin. PMID- 8466213 TI - Peripheral blood mononuclear cells in patients with nonleukemic cutaneous T-cell lymphoma. Reduced proliferation and preferential secretion of a T helper-2-like cytokine pattern on stimulation. AB - BACKGROUND AND DESIGN: Since patients with cutaneous T-cell lymphoma (CTCL) demonstrate several immunologic abnormalities such as elevated serum immunoglobulin levels or reduced natural killer cell activity, we analyzed functional properties of the peripheral blood mononuclear cells in patients with nonleukemic CTCL and healthy donors. RESULTS: After priming with phytohemagglutinin for 3 days, a reduced proliferation in the presence of interleukin 2 and interleukin 4 was found. Limiting dilution technique revealed a diminished number of peripheral blood mononuclear cells from patients with CTCL that were capable of proliferating on interleukin 2 but not on interleukin 4 stimulation. Phytohemagglutinin induced a significantly higher release of interleukin 4 (mean +/- SD, 196 +/- 149.8 pg/mL [n = 19] vs 76.4 +/- 16.4 pg/mL [n = 248]) and a significantly lower secretion of interferon-gamma (24.9 +/- 30.7 U/mL [n = 17] vs 47.5 +/- 43.5 U/mL [n = 18]) in the peripheral blood mononuclear cells of patients with CTCL compared with the peripheral blood mononuclear cells of healthy donors (P < or = .02, U test). CONCLUSION: These functional characteristics can be explained by an imbalanced T helper-1/T helper-2 system and allow speculations concerning clinical features such as elevated immunoglobulin serum levels and reduced cytotoxic activity in patients with CTCL. PMID- 8466214 TI - Sneddon's syndrome. A long-term follow-up of 21 patients. AB - BACKGROUND AND DESIGN: Twenty-one patients with histologically proven Sneddon's syndrome were followed up in a retrospective study. We report on their detailed clinical courses and extensive follow-up examinations. RESULTS: Incidence is estimated at four cases per million population per year. Nonspecific prodromal symptoms (headache, dizziness) frequently (80%) precede livedo racemosa for 3.5 and (multi)focal neurological symptoms of fully developed disease for 9 years followed by progressive cognitive impairment (60%) 10 years later. Involvement of fundi, peripheral nerves, heart, and kidneys is frequent (50% to 70%) yet usually asymptomatic. Some symptoms prove irreversible (livedo racemosa, multifocal cerebral lesions on imaging, or creatinine clearance), whereas other symptoms tend to resolve after days to years (many focal neurological symptoms, some electrocardiographic changes, or hypertension). Mortality is calculated at 9.5% within an average observation time of 6.2 years. Laboratory findings, including antiphospholipid antibodies, are normal except for elevated erythrocyte sedimentation rates and complement consumption at times of disease progression and increased cholesterol levels parallel to disease extent. Skin biopsy specimens reveal inflammatory findings ("endothelitis") of small- to medium-sized arteries followed by subendothelial proliferation and fibrosis. Hypertension is the only risk factor significantly associated with a more severe course of the disease; no medication proved effective. CONCLUSIONS: Sneddon's syndrome is an often unrecognized, slowly progressive, systemic disease with evidence of vasculitic origin. PMID- 8466215 TI - Confocal laser scanning microscopic and immunoelectron microscopic studies of the anatomical distribution of fibrillar IgA deposits in dermatitis herpetiformis. AB - BACKGROUND AND DESIGN: The fibrillar immunofluorescent pattern of IgA deposition in dermatitis herpetiformis is considered by most authorities to be a variant of the granular IgA pattern. It has been hypothesized that the fibrillar vs the granular pattern is related to longitudinal vs transverse sectioning of affected dermal microfibril bundles. However, direct evidence for this possibility has yet to be presented. Confocal laser scanning microscopy and immunoelectron microscopy were performed to determine the anatomical distribution of fibrillar IgA deposits, using skin specimens from a patient with typical fibrillar IgA deposition. OBSERVATIONS: Confocal laser scanning microscopy showed numerous fibrils stained with anti-IgA extending from the dermoepidermal junction to a depth of 50 to 110 microns in the dermis. They crossed each other at various angles to form a three-dimensional network. Immunoelectron microscopy demonstrated a diffuse dispersion of immune deposits on the surface of microfibrils of dermal microfibril bundles, with sporadic distribution of small aggregates, 0.1 to 0.3 micron in diameter. CONCLUSIONS: To our knowledge, this is the first article to present evidence for the actual distribution of fibrillar IgA. Insofar as the present case is concerned, the distribution of fibrillar IgA is greatly at variance with that indicated in previous reports on granular IgA. However, studies on more cases should be conducted to determine whether this is a distinctive feature of the fibrillar type of IgA deposition. PMID- 8466216 TI - Angiokeratoma corporis diffusum with glycopeptiduria due to deficient lysosomal alpha-N-acetylgalactosaminidase activity. Clinical, morphologic, and biochemical studies. AB - BACKGROUND: Angiokeratoma corporis diffusum is a prominent cutaneous feature of certain lysosomal storage diseases. In this article, the clinical, morphologic, and biochemical features of a new, adult-onset lysosomal disease with angiokeratoma are described. OBSERVATIONS: A 46-year-old Japanese woman had diffuse angiokeratoma, mild intellectual impairment, and peripheral neuroaxonal degeneration. The angiokeratoma first appeared on her lower torso when she was 28 years old, and then it became diffusely distributed. Histopathologically, the telangiectasia had localized hyperkeratosis; ultrastructural examination revealed clear cytoplasmic vacuoles in all dermal cells, particularly in vascular and lymphatic endothelial cells and in eccrine sweat gland cells. The lysosomal pathologic features and increased urinary excretion of O-linked glycopeptides suggested the deficiency of a specific glycosidase. Enzyme analyses revealed less than 2% of normal alpha-N-acetylgalactosaminidase activity and the absence of immunodetectable enzyme protein. Her two unaffected children had half-normal alpha-N-acetylgalactosaminidase levels, consistent with the autosomal recessive inheritance of the enzymatic defect. CONCLUSIONS: Since this enzyme deficiency was previously identified in patients with an infantile form of inherited neuroaxonal dystrophy, the occurrence of the enzymopathy in the 46-year-old proband described herein represents an adult-onset form of alpha-N acetylgalactosaminidase deficiency. This newly recognized entity should be considered in the differential diagnosis of angiokeratoma corporis diffusum. PMID- 8466217 TI - Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement. AB - BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening disease with severe mucocutaneous shedding. Although it is widely accepted that immune mechanisms are at play, the pathophysiology of TEN is still unknown. We studied the blister fluid inflammatory cells in three drug-related cases to further define the suspected T-cell involvement in TEN. OBSERVATIONS: A peripheral blood lymphopenia, especially of CD4+ T lymphocytes, was associated with a high lymphocytic cellularity of the blister fluid. In two cases, immunophenotyping of blister fluid lymphocytes showed a predominance of the CD8 phenotype. Furthermore, using two-color flow cytometry in one patient, we could show the predominance of CD8+ CD29+ lymphocytes and CD45RA- negative cells. CONCLUSIONS: Our findings point to a cutaneous recruitment of antigen-primed and cytotoxic T cells in TEN, further supporting the involvement of CD8+ lymphocytes in TEN pathogenesis and its immune mediation. PMID- 8466218 TI - Erythema induratum of Bazin. Evidence of T-lymphocyte hyperresponsiveness to purified protein derivative of tuberculin: report of two cases and treatment. AB - BACKGROUND AND DESIGN: Erythema induratum of Bazin, a chronic form of nodular vasculitis, may be associated with chronic infections by Mycobacterium tuberculosis. However, the true origin of the disease is a subject of speculation and remains elusive. Two female patients (58 years old and 33 years old) with a minimum 10-year history of chronic tender ulcerating nodules on the lower aspects of the legs were studied both clinically and in the response of their peripheral T cells to purified protein derivative of tuberculin. RESULTS: Both patients with no previous history of tuberculosis had strongly positive skin test results at a Mantoux 10(-4) dilution (1 unit of purified protein derivative). In response to full-course triple-agent (isoniazid, rifampicin, and ethambutol) chemotherapy, a complete remission of clinical symptoms was seen in both cases and no relapse occurred after discontinuation of therapy. A marked increase in peripheral T lymphocyte response to purified protein derivative was found before onset of and during successful therapy. CONCLUSIONS: The present clinical observations together with the pronounced cellular response to purified protein derivative suggest a tuberculous origin of erythema induratum of Bazin. PMID- 8466219 TI - Desipramine-induced blue-gray photosensitive pigmentation. AB - BACKGROUND: Blue-gray pigmentation of the skin can be elicited by several medications. We report the first case (to our knowledge) of desipramine-induced photosensitive blue-gray pigmentation. OBSERVATIONS: Diffuse blue-gray pigmentation on sun-exposed surfaces was noted in a healthy 48-year-old woman who had been taking desipramine hydrochloride for 8 years. Ultrastructural studies demonstrated the presence of melanin and homogeneous electron-dense material in the dermis. CONCLUSIONS: We conclude that tricyclic antidepressant agents represent another class of medications responsible for blue-gray cutaneous pigmentation. PMID- 8466220 TI - Intralesional steroid injection after nerve block anesthesia in the treatment of orofacial granulomatosis. AB - BACKGROUND: The facial disfigurement produced by orofacial granulomatosis causes enormous embarrassment. None of the many therapies recommended is reliably successful. Oral corticosteroids cause significant side effects and repeated injections of small quantities of triamcinolone are painful. We have injected large volumes of triamcinolone after numbing the lips using nerve block anesthesia. OBSERVATIONS: Nine patients (six males and three females, aged 10 to 47 years) with orofacial granulomatosis were investigated. No evidence of an allergic cause was found using patch or contact urticaria tests. Eating chocolate produced lip swelling in one man, and his lip shrank in size after avoiding this for 12 months. Five patients, aged 10 to 24 years, were treated with high-volume intralesional triamcinolone injections (3 to 10 mL of 10 mg/mL) after first numbing the lips using infraorbital nerve branch and mental nerve block. After 6 weeks, the lip size returned to normal in four patients and was reduced in a fifth. One patient was injected on four occasions over a 2-year period; in four other patients treated once, lip size remained reduced for over 10 months. CONCLUSION: Intralesional triamcinolone reduces lip swelling in patients with orofacial granulomatosis. Numbing the lips by nerve block anesthesia before triamcinolone injection enables adequate volumes and repeated injections to be given painlessly. PMID- 8466221 TI - The biology of skin grafts. Skin grafts as pharmacologic agents. AB - BACKGROUND: Skin grafting is commonly used to treat nonhealing wounds. However, how skin grafts help to heal wounds is not entirely known. Why epithelium from grafted skin is able to migrate and cover these wounds, while epithelium at the edge of nonhealing wounds is unable to, is a long unanswered biologic question. OBSERVATIONS: The recent use of cultured epithelial allografts has rekindled interest in the biology of skin grafts. Replaced, even in chronic wounds, by recipient epithelium, cultured epithelial allografts appear to work by providing a potent stimulus to healing imparted by the graft itself. Based on this, we have reassessed how skin autografts help to heal wounds and hypothesize that, in a similar fashion, autografts may work not only by replacing tissue but also by providing a stimulus for healing. CONCLUSIONS: We suggest that skin grafts may work not only as tissue replacement but as pharmacologic agents that provide a stimulus for healing. We believe that, someday, it may be possible to augment the stimulatory properties of donor skin to speed healing of the recipient wound. PMID- 8466222 TI - Dermatology in Japan. PMID- 8466223 TI - The immunopathogenesis of cutaneous T-cell lymphoma. Abnormal cytokine production by Sezary T cells. PMID- 8466224 TI - An anemic woman with sparse telangiectases. Osler-Weber-Rendu disease. PMID- 8466225 TI - Erythematous plaques on the eyelids. Discoid lupus erythematosus (DLE). PMID- 8466226 TI - An ulcerated plaque in a gay man. Cutaneous cryptococcosis. PMID- 8466227 TI - Hemorrhagic Darier's disease. PMID- 8466228 TI - Acute undifferentiated myeloblastic leukemia revealed by specific hemorrhagic bullous lesions. PMID- 8466229 TI - Pentoxifylline suppresses allergic patch test reactions in humans. PMID- 8466230 TI - Alopecia totalis and topical mustine. PMID- 8466231 TI - Rupia syphilitica. PMID- 8466232 TI - Ectodermal dysplasia in Cape Verdian families. PMID- 8466233 TI - Alcohol abuse in adolescence: an update. PMID- 8466234 TI - Androgen insensitivity syndrome. PMID- 8466235 TI - An update on Laron syndrome. PMID- 8466236 TI - Operation for gastro-oesophageal reflux associated with severe mental retardation. AB - One hundred and seventy six children with severe mental retardation underwent a fundoplication for considerable gastro-oesophageal reflux. There were six 'early' (3%) deaths and five 'late' deaths. Major complications developed in 17 (10%) children whereas 86 (49%) had 'minor' complications. A revision operation was required in 27 patients. Overall 142 (81%) children achieved a good result. In spite of the high complication rate and the need for a secondary operation in 15% of the patients, the quality of life for these children and their parents and carers is greatly improved by antireflux surgery. PMID- 8466237 TI - Treatment of croup with nebulised steroid (budesonide): a double blind, placebo controlled study. AB - The aim of this prospective, randomised, double blind study was to evaluate whether nebulised local steroid treatment is effective in the treatment of croup. Thirty six infants and children (0.4-4.9 years of age) admitted to hospital with moderate to severe croup were allocated to receive either 2 mg nebulised budesonide (20 children) or saline (16 children). Disease severity was assessed by a clinical total croup score based on stridor, cough, retractions, dyspnoea, and cyanosis. In addition the overall clinical impression was evaluated (0-100). Two hours after treatment there was a significant improvement in the total croup score in the group treated with budesonide (8 to 4.5), but not in the group treated with saline (8 to 8). Furthermore, the overall clinical impression assessment score decreased significantly (50 to 25) in the group treated with budesonide, whereas it remained constant in the placebo group (60 to 62). The total croup score and overall clinical severity were significantly better in the group treated with budesonide than in the placebo group. No side effects were observed. The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children and infants with moderate to severe croup. PMID- 8466238 TI - Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension. AB - The steroid sparing effect of nebulised budesonide suspension was assessed in a double blind placebo controlled parallel group study of 36 preschool children with severe asthma who were dependent on treatment with oral steroids. Nebulised budesonide suspension significantly reduced the requirement for treatment with oral steroids, and produced a marked improvement in overall health as scored on a visual analogue scale during the clinic visits. This study shows a significant step forward in the prophylactic treatment of asthma in children under the age of 3 years, in whom the efficacy of many other nebulised treatments has been questioned. PMID- 8466239 TI - Cardiac rhabdomyomas and their association with tuberous sclerosis. AB - A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas. PMID- 8466240 TI - Protein restriction in chronic renal failure. AB - The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1 g/kg/day) or the control group. All children were followed up by the same paediatrician and dietitian. After a follow up period of three years there was no significant difference in glomerular filtration rate between children on a protein restricted diet and children of the control group. There was no significant difference in weight with respect to height and height SD score between the protein restricted and the control group. Compliance with the protein restricted diet, as indicated by the prospective diet diaries and the serum urea:creatinine ratio, was good. This study shows that children with chronic renal failure do not benefit from a protein restricted diet. PMID- 8466241 TI - Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age. AB - The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate. PMID- 8466242 TI - Evaluation and audit in a paediatric disability service. AB - Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally. PMID- 8466243 TI - Rapid diagnosis of malignancy using flow cytometry. AB - The rapid and accurate diagnosis of childhood malignancy is important both in the planning of appropriate treatment and in relieving the inevitable family anxiety. The use of flow cytometry to analyse monoclonal antibody coated single cell suspensions is widely accepted as having increased the speed and accuracy of diagnosis in leukaemias, though its use in solid tumour diagnosis is not widely reported. Ten cases of childhood malignancy in whom the diagnosis was initially made by flow cytometry and subsequently confirmed histologically are described. The technique has a number of advantages. Only a small sample is required as the analysis is carried out on a single cell suspension, the method is rapid, a diagnosis being reached within three hours of receipt of the sample, and information is obtained on cell lineage and stage of differentiation. Diagnostic accuracy is good when compared with histological results. PMID- 8466244 TI - Lack of lipolytic response in infants after endotracheal intubation. AB - The sympathoadrenal response to endotracheal intubation was investigated in nine infants 2-4 months old and in eight adults 23-45 years old at the start of inguinal hernia operations. In both infants and adults, heart rate and diastolic blood pressure increased significantly immediately after intubation. In both groups, moreover, there was a mean (SD) reduction in microvascular blood flow in the abdominal skin (infants -21 (14)%, adults -14 (7)%) and in the adipose tissue (infants -7 (4)%, adults -5 (4)%). However, the plasma glycerol concentration did not increase in the infants whereas it increased in the adults by 50 (12)%. In conclusion, infants and adults showed similar circulatory reactions during endotracheal intubation but the markedly increased lipolysis rate observed in adults was not seen in the infants. This may indicate that catecholamine induced lipolysis in vivo as well as in vitro is poor during infancy. PMID- 8466245 TI - Unusual cyclosporin related neurological complications in recipients of liver transplants. AB - In a series of 256 recipients of paediatric liver transplants, from 1984 to 1990, four patients presented with sudden onset seizures not explained by conventional work-up. None had a family or personal history of seizures. Infectious causes were excluded. There were no glucose or electrolyte disturbances. Seizures were not induced by systemic or intracranial hypertension. One child out of four had transient white matter and cortex focal lesions on computed tomography of the brain. One to 10 days before seizures all four children presented with supratherapeutic concentrations of serum cyclosporin that were determined by a non-specific method that measured the parent compound plus its metabolites. The supratherapeutic concentrations were not found with the specific method measuring cyclosporin alone. It is concluded that these seizures may correspond to a toxic effect of cyclosporin, probably due to one or several metabolites, as suggested by the discrepancy between specific and non-specific methods of determination. PMID- 8466246 TI - Cerebral aspergilloma in a child with autosomal recessive chronic granulomatous disease. AB - A 2 year old girl presented with epilepsy 16 months after being diagnosed as having autosomal recessive chronic granulomatous disease. Computed tomography showed a cerebral mass which was surgically removed and proved histologically to be an aspergilloma. This case illustrates the application of molecular diagnostic techniques to the diagnosis of chronic granulomatous disease. The occurrence of, and unusual reaction to, cerebral aspergillus infection indicates the need to consider this possibility in the differential diagnosis of mass lesions in chronic granulomatous disease. Furthermore, it is clear that autosomal recessive chronic granulomatous disease cannot be considered to be a clinically mild form that is exempt from major neurological complications. PMID- 8466247 TI - Rhizomelic chondrodysplasia punctata with isolated DHAP-AT deficiency. AB - An infant with the characteristic phenotype of classical rhizomelic chondrodysplasia punctata was found to have an isolated deficiency of the peroxisomal enzyme acyl CoA dihydroxyacetone phosphate acyltransferase (DHAP-AT). All other peroxisomal functions measured were found to be normal. Previously described in one other case report, this confirms the existence of another distinct form of peroxisomal disorder characterised biochemically by a deficiency in de novo plasmalogen biosynthesis only. PMID- 8466248 TI - Nasal dermoids: the significance of a midline punctum. AB - Nasal dermoids are rare and their diagnosis is often delayed until complications occur. Signs such as a midline nasal punctum may be noted at birth but the significance of this finding frequently passes unrecognised. The cases are reported of two patients which illustrate the typical presentation of these lesions and their subsequent management is discussed. PMID- 8466249 TI - From cot death to infant triggered ventilation. PMID- 8466250 TI - Recommendations on the dietary management of phenylketonuria. Report of Medical Research Council Working Party on Phenylketonuria. PMID- 8466251 TI - Physical education and the national curriculum. PMID- 8466252 TI - Atopy, bronchial responsiveness, and symptoms in wheezy 3 year olds. PMID- 8466253 TI - Serum IgG titres against Pseudomonas aeruginosa. PMID- 8466254 TI - Audit of screening for congenital hypothyroidism. PMID- 8466255 TI - Is hearing really assessed after bacterial meningitis. PMID- 8466256 TI - Near fatal haemorrhage from the superior sagittal sinus in Adams-Oliver syndrome. PMID- 8466257 TI - Rett syndrome and the 4th metatarsal. PMID- 8466258 TI - How does exogenous surfactant work? PMID- 8466259 TI - Neonatal blood glucose concentrations: metabolic effects of intravenous glucagon and intragastric medium chain triglyceride. AB - Neonatal hypoglycaemia is a common clinical problem and the traditional treatment for the condition is intravenous glucose administration. The glycaemic effects of two additional treatments were investigated, in a randomised trial, in 23 neonates who were receiving intravenous glucose as treatment for hypoglycaemia. Eleven infants received an intravenous bolus dose of glucagon (200 micrograms/kg) and 12 infants received intragastric medium chain triglyceride (MCT) (5 ml/kg). Blood concentrations of glucose and intermediary metabolites were measured before and one hour after treatment, and, using stable isotope infusion, glucose production rates were calculated. After glucagon, there was a mean rise in blood glucose concentration of 1.6 mmol/l and in the glucose production rate of 2.6 mg/kg/min. After MCT, there was a small mean rise in blood glucose concentration of 0.4 mmol/l, but the effect of MCT on glucose production rate was variable. Intravenous bolus glucagon administration exerted a glycaemic effect which was associated with an increase in glucose production rate. The use of glucagon, as an alternative treatment to intravenous glucose, should be investigated further. PMID- 8466260 TI - Metabolic adaptation in small for gestational age infants. AB - Hypoglycaemia has long been recognised as a feature of the failure of metabolic adaptation in infants who are small for gestational age (SGA). This study examined the process of metabolic adaptation by measuring, longitudinally, the concentrations of metabolic fuels and substrates in 33 SGA infants in the first postnatal week, and relating these to cross sectional data in 218 infants of appropriate weight for gestational age (AGA). SGA term infants had higher mean blood lactate concentrations than AGA term infants at delivery (2.98 v 2.10 mmol/l) and in the first few postnatal hours (3.05 v 1.91 mmol/l). Subsequently, although there were no differences in blood glucose concentrations, SGA term infants had lower mean ketone body concentrations (for example day 2: 0.07 v 0.41 mmol/l), and failed to mount a ketogenic response to low blood glucose concentrations. At birth, SGA preterm infants had lower mean blood glucose concentrations than AGA preterm infants (3.17 v 4.16 mmol/l), but there were few postnatal metabolic differences between the two groups. Mean blood glucose concentrations did not differ between AGA and SGA preterm infants. For variables that differed between the groups, multiple regression analysis suggested that both the degree and asymmetry of growth retardation were related to the severity of the metabolic abnormalities. These data suggest that, although there are early metabolic differences between SGA and AGA infants, it is possible that current clinical management is effective in preventing subsequent hypoglycaemia. This is important because of the failure of SGA infants to mount a ketogenic response. PMID- 8466261 TI - Hormonal and metabolic response to hypoglycaemia in small for gestational age infants. AB - Little is known of the ability of hypoglycaemic infants who are small for gestational age (SGA) to mount the coordinated hormonal and metabolic counterregulatory response that is seen in healthy older subjects during glycopenia. This response was studied in 22 SGA infants (birth weight < 10th centile) by measuring the blood concentrations of glucose, intermediary metabolites, and glucoregulatory hormones. Plasma non-esterified fatty acid and blood ketone body concentrations were low, even when blood glucose concentrations were low. Plasma insulin and glucagon varied widely (< 1.0-53.1 mU/l and 16.6 87.1 pmol/l, respectively). Concentrations of noradrenaline and glucagon were raised, but cortisol and adrenaline were lower than those found in hypoglycaemic adults. There was no relationship between the concentration of any hormone and blood glucose concentration. We postulate that hypoglycaemia and the failure to mobilise alternative fuels in some SGA infants is secondary both to a poorly coordinated counterregulatory hormone response and to a peripheral insensitivity to the actions of the hormones. Those infants, who fail to mount a counterregulatory response, should be identified by accurate and reliable blood glucose monitoring, and an adequate exogenous supply of energy, either enteral or parenteral, should be ensured. PMID- 8466262 TI - The role of pancreatic insulin secretion in neonatal glucoregulation. I. Healthy term and preterm infants. AB - The glucoregulatory role of insulin in adult subjects is undisputed. However, less is known about the secretion of insulin and its actions in the neonatal period, either for healthy subjects, or for those at risk of disordered blood glucose homoeostasis. The relationships between blood glucose and plasma immunoreactive insulin concentrations were therefore examined in 52 healthy children (aged 1 month-10 years), 67 appropriate birth weight for gestational age (AGA) term infants, and 39 AGA preterm neonates. In children and AGA neonates, plasma immunoreactive insulin concentration was positively related to blood glucose concentration. However, although both groups of neonates had significantly lower blood glucose concentrations than children, plasma immunoreactive insulin concentrations were significantly higher in both term and preterm neonates, when compared with children. The variation in plasma immunoreactive insulin concentrations was greater for neonates than for children. These data suggest, that compared with older subjects, plasma immunoreactive insulin concentrations are high in newborn babies and that neonatal pancreatic insulin secretion is less closely linked to circulating blood glucose concentrations. There are important implications for the interpretation of studies in hypoglycaemic and hyperglycaemic neonates. PMID- 8466263 TI - The role of pancreatic insulin secretion in neonatal glucoregulation. II. Infants with disordered blood glucose homoeostasis. AB - Some neonates, such as those who are preterm or small for dates, become hypoglycaemic or hyperglycaemic. These disorders represent a failure of neonatal metabolic adaptation, but the underlying mechanisms are unclear. Data from studies of hypoglycaemic and hyperglycaemic infants were reviewed in the light of new data from studies of healthy neonates. Data from 28 neonates, who had disordered blood glucose homoeostasis, were analysed to determine the interrelationships between circulating concentrations of glucose, intermediary metabolites, glucagon and insulin, and glucose production rates. Blood glucose concentrations ranged from 2.5 to 26.1 mmol/l, and glucose production rates from 0 to 19.2 mg/kg/min. Blood glucose concentrations were positively related to intravenous glucose infusion rates and to glucose production rates. A negative relationship existed between plasma glucagon and blood glucose concentrations, but there was a wide variation in plasma insulin levels at all blood glucose concentrations. No relationship between either plasma insulin or glucagon concentration and glucose production rate was shown. It is concluded that in neonates with disordered blood glucose homoeostasis, blood glucose concentration is influenced by the rate of administration of glucose, with less precise internal control mechanisms than older subjects. This emphasises the importance of blood glucose monitoring and careful prescribing of exogenous glucose by clinicians caring for such infants. PMID- 8466264 TI - Outcome at 8 years for children with birth weights of 1250 g or less. AB - The educational, motor, and behavioural performance of a hospital based cohort of 51 children aged 8 years with birth weights of 1250 g or less is reported, as part of a longitudinal study. Compared with age, race and sex matched classmates, who were examined at school at the same visit, the very low birthweight (VLBW) group performed less well on the basic mathematics test A, the Schonell spelling test, and the test of motor impairment. Reading performance was also poorer in this group. Twenty three (45%) VLBW children were having difficulty with one or more school subjects compared with 11 (19%) controls, and 15 (26%) had difficulties in two or more areas, compared with three (5%) controls. Parents of VLBW children reported a similar frequency of behavioural problems to controls but teachers identified characteristics typical of emotional disorders and overactivity more frequently among the VLBW group. Motor testing at 6 years of age was the best predictor of school problems at 8 years, correctly identifying 15/16 children with multiple problems with a low (33%) positive predictive value but a high (98%) negative predictive value. Children with birth weights of 1250 g or less and no major impairment have a high frequency of learning difficulties that become more apparent with advancing age. Such problems may be predicted at an earlier age by detailed motor testing. PMID- 8466265 TI - Double blind trial of recombinant human erythropoietin in preterm infants. AB - Twenty four infants between 27 and 33 weeks' gestation were recruited into a double blind study to investigate the use of recombinant human erythropoietin (r HuEpo) for the prevention of anaemia of prematurity. Between 50 and 150 U of r HuEpo (n = 16) or placebo was administered subcutaneously twice a week from 7 days of age until discharge. There was a significant increase in the reticulocyte count in infants receiving r-HuEpo sustained from the second week of treatment until discharge compared with placebo. There was a reduction in the number of transfusions required in the r-HuEpo group with only 47% requiring a transfusion compared with 87% in the placebo group. During treatment with r-HuEpo there was a significant rise in the red cell folate concentration, a significant fall in the ferritin concentration, and a significantly higher percentage of haemoglobin F at discharge suggesting active erythropoiesis. The study provides strong evidence for the efficacy of r-HuEpo in stimulating erythropoiesis and reducing the requirement for transfusions for anaemia of prematurity. PMID- 8466266 TI - Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency. AB - To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K supplement at birth. The 66 neonates were divided into a control group (17 cases) and a low group (49 cases) according to their values for clotting activity--that is, > or = 20% or < 20% during the first six days of life -and vitamin K was immediately given when the neonates showed values < 20%. In the low group clotting activity gamma-carboxy protein C, free protein S, and protein C activity was significantly decreased to a minimum on day 2 or 3, and increased in parallel after vitamin K administration. Furthermore, they were positively correlated with one another and inversely cor-correlated with the PIVKA-II concentrations. These findings suggest that simultaneous gamma carboxylation of coagulation factors and proteins C and S acts to maintain both coagulation and anticoagulation activities in parallel at various concentrations of vitamin K. The breast milk intake in the group with low values of clotting activity was significantly lower than that in the control group during the first three days of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466267 TI - Pulmonary artery pressure changes in the very low birthweight infant developing chronic lung disease. AB - Pulmonary artery pressure may be estimated non-invasively in the premature newborn infant because of its negative correlation with the time to peak velocity:right ventricular ejection time (TPV:RVET) ratio calculated from the pulmonary artery Doppler waveform. We studied 54 very low birthweight infants on days 1, 2, 3, 7, 14, 21, and 28 after birth. Thirty four infants developed chronic lung disease (CLD). Twenty did not and acted as controls. After correcting the TPV:RVET ratio for heart rate (TPV:RVET(c)), during the first 14 days the TPV:RVET(c) ratio rose progressively in both groups suggesting a fall in pulmonary artery pressure. This occurred at a significantly slower rate in the CLD group. From days 14 to 28 there was a significant fall in the ratio in the CLD group only, suggesting an increase in pulmonary artery pressure. Using CLD as the end point, a TPV:RVET(c) ratio < 0.54 on day 7 had a predictive value of 78% (sensitivity 73%, specificity 65%). This rose to a predictive value of 97% (sensitivity 88%, specificity 95%) on day 28. The non-invasive assessment of pulmonary artery pressure may be useful in the early clinical management of the very low birthweight infant at risk of developing CLD. PMID- 8466268 TI - Long term trigger ventilation in neonatal respiratory distress syndrome. AB - Experience of using an SLE 2000 neonatal trigger ventilator as the sole means of ventilation in 68 infants with respiratory distress syndrome was reviewed. No death or complication was seen in 22 infants with a birth weight above 1500 g. Forty five infants under 1500 g birth weight including 18 infants between 23 and 28 weeks' gestation were trigger ventilated throughout. Six infants died, four of whom were under 28 weeks' gestation. Two infants under 1500 g birth weight sustained a pneumothorax while being ventilated. Nine of 61 infants (15%) had radiological evidence of pulmonary interstitial emphysema, which was mild in seven infants. Intraventricular haemorrhage occurred in 10 babies under 1500 g, four of these being grade III or IV. Twenty two (48%) of the babies under 1500 g required added oxygen at 28 days. The preliminary clinical experience of this trigger ventilator suggests that it is capable of providing respiratory support from birth to extubation in even the most immature infants with respiratory distress syndrome. A controlled clinical trial is now required to compare the safety and efficacy of patient triggered ventilation with conventional neonatal ventilation. PMID- 8466269 TI - Factors associated with respiration induced variability in cerebral blood flow velocity. AB - A consecutive cohort of 73 very low birthweight infants was studied to determine the presence or absence of beat to beat variability in the velocity of blood flow in the cerebral circulation and its relation with respiration. One minute epochs of information included recordings of cerebral blood flow velocity estimated with Doppler ultrasound, blood pressure, spontaneous respiratory activity, and ventilator cycling. Fourier transformation was used to resolve the frequencies present within the one minute epochs and to classify the cerebral blood flow velocity as showing the presence or absence of any respiratory associated variability. A total of 249 recordings was made on days 1, 2, 3, and 7. Forty seven infants showed respiratory variability in cerebral blood flow velocity on 97 occasions, usually during the first day of life. The infants with respiratory associated variability were of lower gestational age and when the respiratory associated variability was present they were more likely to be ventilated and receiving higher inspired oxygen; these associations were shown to be independent of gestational age. There was no significant independent association with brain injury, cerebral blood flow velocity (cm/s), or blood pressure (mm Hg). The findings suggest that artificial ventilation may entrain normal respiratory associated variability in the cerebral circulation but do not provide evidence that it is harmful. PMID- 8466270 TI - Development of bowel habit in preterm infants. AB - The bowel habits in 844 preterm infants were observed during the first 56 days after birth. Delay in the passage of meconium beyond the second day occurred in 32%, and there was an inverse relation between gestational age and the day of first bowel action. Thereafter the increase in frequency of stools passed each day was related directly to the volume of milk ingested. Unfed infants had a modal defecation rate of one stool each day. For each 50 ml/kg increase in the volume of milk ingested the infants showed a further increase of one stool passed each day. Infants fed with human milk passed a greater number and softer stools than those who received cows' milk formula. In the absence of milk feeds an intrinsic pattern of large bowel motor activity, present as early as 25 weeks' gestation, ensures a defecation rate of one stool each day. The effect of enteral nutrition on this inherent motility is governed by the volume and composition of milk feeds, independently of gestational age. PMID- 8466271 TI - Influence of place of delivery on outcome in babies with gastroschisis. AB - In order to determine whether the elective delivery of babies with gastroschisis confers advantages in outcome, the case-notes of all babies referred to Bristol with gastroschisis over a 10 year period were reviewed. Various factors were compared between babies born in Bristol and those born elsewhere in the South West region. One neonate from the outborn group died after transfer to Bristol but otherwise there was no evidence that transfer and elective delivery in Bristol conferred any advantage. The important of effective resuscitation of outborn babies before transfer is emphasised and guidelines for resuscitation given. PMID- 8466272 TI - Resuscitation with intraosseous lines in neonatal units. PMID- 8466273 TI - Should we look after babies less than 800 g? PMID- 8466274 TI - The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia. PMID- 8466275 TI - Dr Ramazzini (1633-1714) and the occupational diseases of midwives and wet nurses. PMID- 8466276 TI - Metabolic acidosis in premature babies. PMID- 8466277 TI - Traumatic neonatal intracranial bleeding and stroke. PMID- 8466278 TI - Brain uptake of amino acids in intravenously fed preterm infants. PMID- 8466279 TI - Lymphokine profiles in contact sensitivity induced by dinitrofluorobenzene and tolerance induced by dinitrothiocyanobenzene. AB - We determined the lymphokines involved in the immune response to epicutaneously applied dinitrofluorobenzene (DNFB), a sensitizer, and dinitrothiocyanobenzene (DNTB), a tolerogen. Hapten-dependent T-cell proliferation and production of interleukin-2, interleukin-3 and interleukin-4 by lymph node cells (LNC) in mice painted with these cross-reactive haptens were measured by specific lymphokine assays. Proliferation of LNC in tolerized animals was lower than in sensitized mice. LNC from DNTB-treated mice produced lower amounts of interleukin-2, interleukin-3 and interleukin-4 than cells from DNFB-painted mice. These results may explain hapten-specific tolerance induced by DNTB which results in deficient production of both type 1 T-helper cell (Th1) and type 2 T-helper cell (Th2) lymphokines in response to hapten re-exposure. Deficient interleukin-4 production by cells from tolerized mice was corrected by the addition of exogenous interleukin-2. The suppressor function of adoptively transferred T cells from animals tolerized with dinitrothiocyanobenzene may be related to a shift in the balance of Th1 and Th2 lymphokines in favour of the latter, since recipient T cells might provide the source of interleukin-2 that induces interleukin-4 production by donor T cells. PMID- 8466280 TI - Effects of tumor necrosis factor-alpha on connective tissue metabolism in normal and scleroderma fibroblast cultures. AB - Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) selectively decreases production of collagens I and III, the major types of collagen in the dermis, and increases production of collagenase in cultured dermal fibroblasts. The effects of TNF-alpha on collagens I, III and VI, fibronectin and collagenase gene expression by fibroblasts derived from normal individuals and patients with systemic sclerosis (SSc) were studied. SSc is characterized by excessive accumulation of collagen in the skin and in certain organs. TNF-alpha inhibited collagen production and mRNA levels of collagens I and III and of fibronectin, and stimulated collagenase activity and collagenase mRNA levels in SSs fibroblasts. Levels of mRNA for alpha 1 (VI) and alpha 3 (VI) collagen and for beta-actin were unaltered in SSc fibroblasts incubated with TNF alpha. Similar results were observed for mRNA levels in normal fibroblasts incubated with TNF-alpha. These results suggest that TNF-alpha could be expected to be beneficial in the treatment of SSc. In addition, our results indicated that collagen-VI expression is regulated independently from expression of collagens I and III, and expression of fibronectin and collagens I and III are regulated in parallel in fibroblasts treated with TNF-alpha. PMID- 8466281 TI - Growth and differentiation stimuli induce different and distinct increases in intracellular free calcium in human keratinocytes. AB - The effect of growth and differentiation stimuli on intracellular free calcium ([Ca2+]i) in cultured human keratinocytes was investigated using micro spectrofluorimetric techniques and the calcium-sensitive dye FURA-2. The mean [Ca2+]i of keratinocytes in 70 microM calcium medium was 104 +/- 3 nM (mean +/- SEM), significantly lower than the transformed keratinocyte line SVK14 (128 +/- 2 nM). When cultured in 2.0 mM calcium medium the [Ca2+]i increased in both normal and transformed keratinocytes to 135 +/- 4 nM and 180 +/- 4 nM, respectively. Keratinocytes grew more slowly in the absence of EGF, but [Ca2+]i was unaltered. Stimulation with EGF (10 ng/ml) induced, over 4 min, a large transient rise in [Ca2+]i up to 230 nm, due to an influx of extracellular calcium. Heterogeneity of keratinocytes was observed with 46% (n = 13) responding, but confluent or differentiated keratinocytes did not respond. TGF--beta (1 ng/ml) reduced cell growth without inducing differentiation and was not associated with any change in [Ca2+]i. The phorbol ester TPA (50 nM) induced irreversible growth arrest and terminal differentiation and increased the [Ca2+]i from 102 +/- 2 nM to 126 +/- 3 nM at 2 h, an effect similar to that of 2 mM extracellular calcium. Addition of 500 nM TPA was associated with a rise in [Ca2+]i, over several minutes to a plateau of 200-300 nM, due to release from internal stores and an influx of extracellular calcium. In normal human keratinocytes an increase in [Ca2+]i appears to be an early event in differentiation, whether induced by calcium or TPA, but not during growth inhibition without differentiation. PMID- 8466282 TI - Adrenal androgen abnormalities in women with late onset and persistent acne. AB - Androgens are an essential prerequisite for the development of acne. The present study was undertaken to characterize the androgen status of women with late onset and persistent acne only and, using the dexamethasone (dex) suppression test, to identify the source(s) of the androgen excess. We measured serum levels of total testosterone (T), free testosterone (FT), androstenedione (delta 4A), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding globulin (SHBG) in 34 healthy control subjects, in 34 women with mild acne and in 29 women with moderate or severe acne. Serum FT, DHT and DHEA-S levels in patients of both acne groups were significantly higher than those in the control subjects. The other hormone levels showed no significant differences between patients and control subjects, and there were no significant differences between the two acne groups in any of the androgen levels. In order to evaluate the ovarian and adrenal contributions to serum androgens in the acne patients, the serum levels of delta 4A, T, DHT and DHEA-S were measured prior to and following 2 weeks of dex therapy. Following the dex test, the DHT and T of adrenal origin were significantly higher in the acne patients than in the control subjects. These results suggest that, in acne patients, hyperandrogenaemia is likely to develop as a result of adrenal androgen excess. In addition, since abnormally high androgen levels are frequently seen in late onset and persist acne, it seems that this condition is likely to be a sign of hyperandrogenism. PMID- 8466283 TI - Racial differences in the in vivo percutaneous absorption of some organic compounds: a comparison between black, Caucasian and Asian subjects. AB - Individual differences exist between patients, and, for topical therapy, differences in skin due to race may be a consideration. Pharmacological response depends upon the percutaneous absorption and the inherent activity of the chemical once absorbed into the biological system. Our objective was to determine the in vivo percutaneous absorption of three test chemicals in human subjects with Asian (A), black (B) and Caucasian (C) ethnic skin. Following a 30 min topical application on the upper outer arm of 1 mumol/cm2 14C-labeled chemical, percutaneous absorption was determined by both urinary excretion and the stripping technique. Amounts absorbed were: for benzoic acid 1.43 +/- 0.27% (SD) (A), 1.07 +/- 0.18% (B), 1.2 +/- 0.19% (C); for caffeine 1.06 +/- 0.17% (A), 1.01 +/- 0.19% (B) and 0.96 +/- 0.12% (C); for acetylsalicylic acid 1.8 +/- 0.31% (A), 1.59 +/- 0.31% (B) and 2.12 +/- 0.36% (C). No statistical difference (P > 0.05) was found in percutaneous absorption of benzoic acid, caffeine or acetylsalicylic acid between Asian, black and Caucasian subjects. PMID- 8466284 TI - Organ culture of human hair follicles in serum-free medium. AB - Human hair follicles were cultured in serum-free media at 31 degrees C in an atmosphere containing 95% O2 and 5% CO2. Results showed that the length of the cultured hair increased time dependently for 96 h. Histological findings revealed that the hair germinative cells maintained their normal morphology throughout the 96 h culture period. DNA synthesis in the hair bulb also increased time dependently for 96 h. Autoradiographs of 3H-thymidine-labelled follicles indicated that they were localized in the germinative cells below Auber's critical line. The effects of minoxidil sulphate on DNA synthesis in this culture system were concentration dependent. Minoxidil sulphate at concentrations of 10( 10), 10(-9) and 10(-8) M significantly increased DNA synthesis compared with DNA synthesis in the control medium. Autoradiographs of the follicles cultured in 10( 10) M minoxidil sulphate showed that 3H-thymidine localized primarily in the germinative cells below Auber's critical line. These results suggest that this organ culture system may be useful for studying DNA synthesis by hair germinative cells in serum-free media. PMID- 8466285 TI - Bound lipids liberated by alkaline hydrolysis after exhaustive extraction of pulverized clavus. AB - In the present study, covalently bound lipids were found in clavus material and their lipid classes were determined by high-performance thin-layer chromatography (HPTLC). Clavus material, pulverized completely in a Mikro-Dismembrator II, was exhaustively extracted three times with chloroform/methanol (2:1, 1:1 and 1:2 v/v) at 80 degrees C for 1 h each time and this sequence of extractions was repeated to obtain the unbound lipid-free residue which was saponified and then extracted with chloroform. The extract proved to comprise several bands of lipids covalently bound through an ester-like linkage. These were identified as free fatty acids, cholesterol, ceramides and glucocerebrosides by HPTLC. However, omega-hydroxy fatty acids were not detected in the lipids. To analyse the fatty acids amide-linked to the bound ceramides, the latter were isolated by preparative HPTLC and subjected to mild acid hydrolysis. Since the bound ceramides constituted neither omega-hydroxy fatty acids nor alpha-hydroxy fatty acids, they were not identified as hydroxyl-acylsphingosines. PMID- 8466286 TI - Casein kinase III activity in psoriasis. PMID- 8466287 TI - The relative contribution of individual polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-p-furans (PCDFs) to toxic equivalent values derived for bulked human adipose tissue samples from Wales, United Kingdom. AB - Five bulked human adipose tissue samples were analyzed for individual polychlorinated biphenyl (PCB) congeners (including selected non-ortho substituted compounds) and polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). Mean sigma PCB and sigma PCDD/F (tetra-through octachlorinated homologues) concentrations were 0.75 microgram/g and 1.22 ng/g adipose tissue respectively. Both the congener patterns and levels detected were similar to those reported by laboratories in other industrialised countries. Each sample comprised of tissue taken from donors within a given locality. However, no obvious relationships were apparent between sampling area, absolute concentrations and congener pattern of PCBs and PCDD/Fs. The contribution of individual PCDD/F and non-ortho-(o), mono-o-, and di-o-substituted PCB congeners to the total calculated toxic equivalent values (sigma TEQ) was assessed for each sample. The main contributions to the sigma TEQ were the mono-o-substituted PCB congeners #118 (TEQ = 42.5 pg/g of lipid), #156 (TEQ = 24.8 pg/g) and #105 (TEQ = 20.7 pg/g), followed by 1,2,3,6,7,8-HxCDD (TEQ = 18.2 pg/g), 2,3,4,7,8-P5CDF (TEQ = 12 pg/g), 1,2,3,7,8-P5CDD (TEQ = 11.5 pg/g), and the non-o-substituted PCB congener #126 (TEQ = 11.3 pg/g). Collectively, these compounds accounted for 80% of the sigma TEQ values. Based on the TEFs proposed by Safe (1990), the overall TEQs calculated for the monitored PCBs, were twice those due to sigma PCDD/Fs. PMID- 8466288 TI - In vitro effects of N-nitrosoatrazine on chromosome breakage. AB - Exposing human lymphocyte cultures to concentrations of N-nitrosoatrazine (NNAT) as low as 0.0001 microgram/ml results in significant elevations in chromosome breakage as well as an increased mitotic index. In contrast, 1,000-10,000-fold greater concentrations of nitrates, nitrites, and/or atrazine was required to produce comparable chromosome damage and, in those cases where the mitotic index was affected, it was decreased. Simultaneous administration of nitrates or nitrites with atrazine caused less chromosome damage than low concentrations of NNAT without affecting the mitotic index, illustrating that metabolic conversion of contaminants with minimal genotoxicity can give rise to compounds such as NNAT which are even more genotoxic. PMID- 8466289 TI - The effect of industrial pollution on mercury levels in water, soil, and sludge in the coastal area of Motril, southeast Spain. AB - The total concentration of mercury was determined in samples of water, soil and sludge from the Mediterranean coastal area of Southeast Spain (Motril), where Hg contamination is produced primarily by a local paper mill. Samples were taken at surface level in a 5 Km radius from the factory. The total Hg concentrations varied from 0.117 to 0.760 microgram/g in soil and sludge, and from ND to 2.088 micrograms/L in water. A negative correlation was observed between the distance of the sampling station from the mill and the concentration of Hg in the soil and sludge samples. Similarly, an increase in Hg concentration was observed in the freshwater and wastewater after passing close to the factory. PMID- 8466291 TI - Coplanar polychlorinated biphenyl congener levels and patterns and the identification of separate populations of harbor seals (Phoca vitulina) in Denmark. AB - Blubber samples from 21 harbor seals (Phoca vitulina), found dead on Danish beaches during the morbilli virus epidemic in 1988, have been analyzed for toxic coplanar chlorinated biphenyl (CB) congeners. The 21 samples consist of seven samples from 1-2-year-old animals (both males and females) from each of three geographical separate locations: The Limfjord, the Kattegat, and the Wadden Sea. The level of the CBs, defined as the sum of all the measured CB congeners, were highest in the samples from the Wadden Sea and lowest in the Limfjord samples. The quotient between highest level and lowest level was 4. Toxic equivalency factors given by Safe (1990) was used for calculation of the contribution to dioxin-like toxicity from the coplanar CB congeners, and the result was compared to literature data on polychlorinated dibenzo-p-dioxins and -dibenzofurans in harbor seal. CB congeners CB-118, CB-156, CB-157, and CB-105 were major contributors to sigma TEQ in all samples. The patterns of polychlorinated biphenyl congeners in harbor seals from the three locations were compared by principal component analysis. The two first principal components could separate the samples in groups corresponding to each of the three geographical locations. The geographical and biological variations were estimated from the data. It was shown, that the geographical variation was the largest. Possible reasons behind the geographical variation in CB congener patterns are discussed. PMID- 8466290 TI - The growth response of the green alga Chlorella vulgaris to combined divalent cation exposure. AB - Using the growth response of the green alga Chlorella vulgaris as a model system, the effects of combinations of the environmentally active cations Cd, Co, and Cu were evaluated. The 96-h static EC50 for these cations to C. vulgaris were, respectively, 0.89 microM, 9.0 microM, and 2.8 microM, yielding a toxicity series such that Cd > Cu > Co. The cation combinations of Cd + Cu, and Cu + Co acted synergistically, while Cd + Co, and the tri-metallic combination Cd + Cu + Co resulted in antagonistic interactions. Examination of these toxic combinations at 24, 48, 72, and 96 h indicate that the cellular response is not a uniform one. Failure of energy dispersive X-ray spectrophotometric analysis to demonstrate any intracellular incorporation of these cations (except for a weak cytoplasmic Cu peak at the 8.0 KEV position) suggests that the toxic actions of these cations at EC50 concentrations are exerted at the level of the plasma membrane. PMID- 8466292 TI - Effects of air pollution on passerine birds and small mammals. AB - The effects produced by emissions from coal-fired power plants, including mainly SO2, NOx and particulates, on natural populations and caged specimens of birds and small mammals were studied. The field-captured species used to evaluate these effects were passerine birds: Parus major (coal tit) and Emberiza cia (rock bunting), and the rodent Apodemus sylvaticus (wood mouse). In parallel to this study on animals captured in the field, we used other animals, Mus musculus (house mouse) and Carduelis carduelis (goldfinch) which were placed in cages near the source of pollution. Some of the animals were killed and their tracheas were removed and prepared for conventional optic studies (1000x) and electron microscopy (TEM and SEM). The results show that atmospheric air pollutants from coal-fired power plants produce alterations in the tracheal epithelium. In passerine birds, an increase in the mucus which covers the tracheal epithelium, shortening of the cilia, and increase in the number of secretory granules and vesicles were observed. In mammals, variation of the uniformity of the pseudostratified epithelium with a wide stratum of mucus, shortening of the cilia, and increase in the number of secretory granules were observed. PMID- 8466293 TI - Effects of organic fertilizers on aldicarb soil biodegradation in sugar beet crops. AB - In the present work, the influences of several organic fertilizer treatment regimens were compared as to their slowing down effect on aldicarb soil metabolism in a sugar beet crop. The organic fertilizers treatment schemes had been repeatedly applied in the past 30 years, according to a 3-year rotation cycle. The following organic fertilizers treatment regimens--which are the main ones used in the agronomy practice--were compared: Treatment 1: no organic fertilizer at all; treatment 2: 40 tons cow manure ha-1; treatment 3: 40 tons pig slurry ha-1 + green manure + crop wastes; treatment 4: green manure + crop wastes; treatment 5: straw cereal wastes alone. A sugar beet crop was sown in April 1991, 1 kg aldicarb ha-1 being applied in granulates in the sowing furrow. During the 2.9 first crop months, the soil half-lives of the sum of the insecticide S(-)+SO(-)+SO2-aldicarb in the sowing line in the 0-25 cm surface soil layer were 21.6, 44.4, 39.6, 35.7, and 30.3 days in the treatments 1, 2, 3, 4, and 5 treated plots, respectively. The organic fertilizers soil treatments thus increased the persistence of the total insecticide compounds soil concentrations, and probably also the insecticide protection efficiencies. Comparison of the results obtained here with the ones previously obtained with other crop trials, herbicides and soil insecticides, suggests that the soil organic matter is the most efficient to slow down the insecticides soil biodegradation, compared to the old humus originating from the organic fertilizers treatments made more than one year ago.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466294 TI - Family pesticide use and childhood brain cancer. AB - The relationship between family pesticide use and childhood brain cancer was examined in a case-control study. Telephone interviews were conducted from June 1989 through March 1990 with the natural mothers of 45 childhood brain cancer cases, 85 friend controls, and 108 cancer controls. In comparisons to friend controls, significant positive associations were observed for use of pesticides to control nuisance pests in the home, no-pest-strips in the home, pesticides to control termites, Kwell shampoo, flea collars on pets, diazinon in the garden or orchard, and herbicides to control weeds in the yard. In comparisons to cancer controls, significant positive associations were observed for use of pesticide bombs in the home, pesticides to control termites, flea collars on pets, insecticides in the garden or orchard, carbaryl in the garden or orchard, and herbicides to control weeds in the yard. In general, positive associations in comparisons to one control group were supported by elevated odds ratios in comparisons to the other control group. Several potentially important associations were identified in this study. However, small sample sizes, potential recall bias, multiple comparisons, and lack of detailed exposure verification require further research to confirm these findings. PMID- 8466295 TI - Factors affecting inter-individual variation in human plasma cholinesterase activity: body weight, height, sex, genetic polymorphism and age. AB - The influence of body weight, height, age and sex on plasma cholinesterase activity (ChE) in 650 males and 437 females with ChE-1 phenotype U (genotype ChEuChEu or ChEuChEs) or UA (genotype ChEuChEa) was studied in a multiple regression model. ChE was not influenced by age (p > 0.01), but, like other liver synthesized plasma enzymes, highly (p < 0.001) influenced by body weight and height. In a logarithmic scale ChE followed a linear model (R = 0.535, p < 0.001) with randomly distributed residuals, InChE = 3.286-0.308 x ChE-1 phenotype-0.104 x sex + 0.00765 x weight - 0.00723 x height (U = 1, UA = 2; male = 1, female = 2; kg; cm). A simplified model based on body-mass index (BMI = weight divided by squared height, kg/m2), InCHE = 2.016-0.308 x ChE-1 phenotype - 0.091 x sex + 0.0230 x BMI, showed the same goodness-of-fit (R = 0.533). In a non-logarithmic scale both multiple regression models failed to fit cases with high ChE activity. A model for a 'standardized' plasma ChE in which the effects of ChE-1 phenotype, sex, body weight and height are eliminated, is proposed to compare ChE in unmatched population groups when using this enzyme activity as a biomarker in environmental or occupational medicine. PMID- 8466296 TI - Measurements of year-long exposure to tree nursery workers using multiple pesticides. AB - A year-long nurseryworker pesticide exposure study was designed to measure and evaluate the exposure occurring to workers who had the potential for simultaneous exposure to multiple pesticides. This four-State study was conducted in five nurseries (four USDA Forest Service and one State) involved in conifer seedling production. Primary comparisons were made among nursery workers in the Pacific northwest and south central United States. Worker exposure was assessed by using patches attached to clothing, handrinse samples and urine excreted from potentially exposed workers. In addition, dislodgeable residue in rinsate from a water wash of pesticide-treated seedlings was also evaluated. Four different groups of field workers, designated as applicators, weeders, scouts and packers, were included. The pesticide absorbed dose, assessed by urine analysis of pesticide metabolites and the deposition of pesticide on patches attached to the clothing of field workers, was monitored as they performed their duties under normal conditions (e.g., typical clothing, pesticide application). Monitoring was performed for the 14 different pesticides which were used in these nurseries. Seven pesticides were studied in more detail using biological monitoring. For these compounds, metabolites known to be excreted in the urine of exposed humans or other mammals were used to estimate the dose of pesticide absorbed by the exposed workers. The highest percentage of positive samples came from dislodgeable residue samples (8.3%) followed by patch samples (3.2%), handrinse (2.9%), and urine samples (1.3%). To summarize the conclusions from the urinary excretion data, 12 of the 73 nursery workers in the study received a low absorbed dose of pesticide. Biological monitoring revealed that three pesticides (benomyl, bifenox and carbaryl) were found in the urine of some of the workers. Of the 3,134 urine samples analyzed there were 42 positive; 11 urine samples were positive for benomyl, while bifenox was responsible for 13 positives and carbaryl accounted for the remaining 18. The 12-week continuous monitoring of urine showed that metabolites of these materials were rapidly excreted; thus, no build-up in the body is anticipated. Margins of Safety (MOS) calculations were made to provide an assessment of the significance of the exposure. Based on the low frequency of positive urine samples in the study, the low levels of metabolites when they were found, their apparent rapid excretion rate and the No Observed Effect Level (NOEL) data, furnished from other sources, nursery worker exposure to pesticides in these conifer nurseries is below health threatening levels. PMID- 8466298 TI - Toxicological assessment of biodegraded pentachlorophenol: Microtox and fish embryos. AB - A Gram-negative bacterium, Pseudomonas sp. strain SR3, was isolated from soil at a former wood treatment plant in north central Florida. The ability of this bacterium to degrade pentachlorophenol (PCP) was confirmed by growing cells in a basal salts medium in which PCP was the only source of carbon and energy. Degradation from a measured concentration of 39-40 micrograms PCP/ml to 0.0006 micrograms PCP/ml was observed within 120 h of incubation in the presence of PCP induced cells of Pseudomonas sp. strain SR3. The initial cell density in these cultures was 6 x 10(6) cfu/ml. Microtox 5 min EC50 toxicity tests revealed that aqueous solutions of PCP, measured concentrations 39-40 micrograms/ml were toxic but that final biodegraded samples, 0.0006 micrograms PCP/ml were nontoxic. However, bioassays with embryonic inland silversides, Menidia beryllina, showed that the biodegraded samples were embryotoxic or teratogenic. Water containing added PCP at concentrations up to 30 times higher than measured in the final biodegraded samples was less toxic/teratogenic. These results indicate that while biodegradation of PCP was nearly complete, intermediate metabolites of the degradation process or undegraded impurities in PCP were toxic or teratogenic. Thus, the M. beryllina bioassay allows extremely sensitive assessment of toxicity associated with biodegraded environmental pollutants and may be a useful criterion for determining whether bioremediated water or soil is safe for discharge back into the environment. PMID- 8466297 TI - The reproductive effects of dietary heptachlor in mink (Mustela vison). AB - Adult female mink were fed diets containing 0 (control), 6.25, 12.5, and 25 ppm (micrograms/g) technical grade heptachlor prior to and throughout the reproductive period (181 days) to evaluate the effects of heptachlor consumption on reproduction and offspring viability and to assess the extent of placental and mammary transfer of heptachlor epoxide to mink offspring. Feeding 12.5 and 25 ppm resulted in significant reductions in feed consumption and body weights of female mink. Mortality was 0, 8, 67, and 100% for the control, 6.25, 12.5, and 25 ppm groups, respectively. All females in the 25 ppm group died within 88 days. Mink fed the two higher heptachlor diets displayed clinical signs indicative of central nervous system involvement just prior to death. Females were mated with males on the same dietary treatments. Whelping success rates were 67, 83, 27, and 0% for the control, 6.25, 12.5, and 25 ppm groups, respectively. High mortality in the 12.5 and 25 ppm groups accounted for the lack of reproductive success. Gestation length, litter size and birth weight of kits were not significantly affected by adult female consumption of 6.25 ppm heptachlor while kits helped by females on the 12.5 ppm diet weighed significantly less than control kits at birth. Survival of kits in the 12.5 ppm group from birth to three weeks of age was also adversely affected. At three and six weeks of age, kit body weights in both the 6.25 and 12.5 ppm groups were significantly less than body weights in control kits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466299 TI - Oxidative stress in fish cells: in vitro studies. AB - Bluegill sunfish BF-2 fibroblasts were used in the neutral red (NR) cytotoxicity assay to discern the toxicities of hydrogen peroxide (H2O2) and paraquat as indicated by their abilities to induce oxidative stress. The toxicity of H2O2 was markedly enhanced in BF-2 cells treated with the glutathione depleting agents, buthionine sulfoximine (BSO), maleic acid, and chlorodinitrobenzene; similar treatments did not sensitize the BF-2 cells to paraquat, a redox cycling xenobiotic. BSO treated BF-2 cells, however, were sensitized to nitrofurantoin, also a redox cycling chemical. Diethyldithiocarbamate, an inhibitor of superoxide dismutase, only weakly enhanced the sensitivity of the BF-2 cells to H2O2 and paraquat. 1,10-Phenanthroline, a chelator of Fe2+, reduced the cytotoxicity of H2O2 and paraquat, presumably by preventing hydroxyl radical formation in the Fenton reaction. Quin 2 AM, an intracellular chelator of Ca2+, markedly lessened the toxicity of H2O2, but not of paraquat; EGTA, an extracellular chelator of Ca2+, had no effect on the toxicity of H2O2 or paraquat. Apparently, perturbation of intracellular Ca2+ homeostasis is involved in H2O2 toxicity. For comparative purposes, some studies were performed with fathead minnow FHM epithelioid cells, BALB/c mouse 3T3 fibroblasts, and human HepG2 hepatoma cells. The BF-2 fibroblast/NR cytotoxicity red assay was shown to be a suitable model to study oxidative stress in fish. PMID- 8466300 TI - Cadmium, copper and lead in wild rice from central Canada. AB - Samples of wild rice grains available for sale in Manitoba, Canada contained < 0.01-6.2 micrograms/g cadmium, < 0.01-6.7 micrograms/g lead, and 1.6-14.4 micrograms/g copper. Rice originating from Saskatchewan and northern Manitoba contained significantly higher copper concentrations than samples from Ontario and southeastern Manitoba. Larger and heavier grains contained higher lead concentrations per unit weight. Mean content of all three metals per individual grain was exponentially correlated with grain size and weight. Total soluble carbohydrate and soluble protein concentrations were negatively correlated with copper concentrations. PMID- 8466301 TI - Levels of environmental pollutants in flounder (Platichthys flesus L.) and cod (Gadus morhua L.) caught in the waterway of Glomma, Norway. II. Mercury and arsenic. AB - The present study is a survey on mercury and arsenic pollution in two sedentary fish species stationed in or close to the Glomma estuary in the Hvaler archipelago, Norway. Mercury and arsenic were determined individually in 80 flounder (Platichthys flesus L.) and 100 cod (Gadus morhua L.). The fish were caught at five different localities near or in the relatively polluted Glomma estuary. There were significantly higher mercury and arsenic concentrations in fillets of flounder than in fillets of cod (wet weight), 0.15 vs. 0.08 mg/kg and 5.2 vs. 4.1 mg/kg, respectively. Seasonal variation in mercury concentration was only found in flounder, with a significantly higher level in spring than in autumn. A significant increase in mercury content with increasing age was found for both species. For cod, a significantly higher arsenic level was found on the outer stations as compared to the inner stations, while arsenic levels in flounder was less dependent on sampling site. PMID- 8466302 TI - Effects of fasting on distribution and excretion of lead following long-term lead exposure in rats. AB - Lead was given to rats through drinking water containing 100 ppm lead acetate for 20 days. Delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes was significantly lower (p < 0.05) at 20 days after Pb treatment. Erythrocytic ALAD activity was significantly lower (p < 0.05) in fasted rats than in fed rats with or without Pb pretreatment. Serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase activities after 6 days of fasting were significantly higher (p < 0.05) in Pb pretreated rats than in other groups (Pb nontreated fed and fasted rats, and Pb pretreated fed rats). Long periods of fasting strongly enhanced these serum-enzymes elevations induced by lead. Maximum Pb concentrations and total amount in feces increased in rats fasted for 3 days regardless of Pb pretreatment. On the other hand, total amount of Pb in feces of rats fasted for 6 days were not significantly different from the other groups because their fecal volume decreased to about 1% of fed rats. The Pb concentrations of liver, kidney, spleen, and femur increased significantly in Pb pretreated rats compared to in controls, but there were no significant differences between the fed and fasted rats. PMID- 8466304 TI - Ileal pouch-anal anastomosis for ulcerative colitis associated with primary sclerosing cholangitis. PMID- 8466303 TI - Effects of diethylene glycol monomethyl ether on pregnancy and postnatal development in rats. AB - The effects of oral treatment of Wistar rats with diethylene glycol monomethyl ether (diEGME) were examined. In a preliminary dose-finding study with non pregnant rats, diEGME treatment at doses up to 4,000 mg/kg/day on 11 consecutive days decreased relative weights of thymus and pituitary gland, white and red blood cell counts, hemoglobin concentrations and hematocrit levels. In pregnant rats, treatment at doses of > 3,000 mg/kg/day (over gestation days 7-17) caused total resorption of all litters. In teratology and postnatal studies, pregnant rats were treated with diEGME at doses of 0, 200, 600, and 1,800 mg/kg/day from day 7 through 17 of gestation. At 200 mg/kg, there were no adverse effects on either dams, fetuses, or neonates. At 600 mg/kg, dams were not affected, but fetal body weights were decreased, and fetal thymus and ossification were adversely affected. At 1,800 mg/kg, maternal thymus weights and food consumption were decreased, and visceral malformations of the cardiovascular system were seen in 28.0% of the fetuses. Only 6.3% of the pups delivered by dams treated with 1,800 mg/kg of diEGME survived for 4 days after birth. Thus, diEGME was teratogenic in Wistar rats, but the spectrum differed from that in Sprague-Dawley rats. In addition to teratogenicity, diEGME had significant adverse effects on postnatal development. The most sensitive organ to diEGME was the thymus in both dams and fetuses. PMID- 8466305 TI - Complications and risk factors after ileal pouch-anal anastomosis for ulcerative colitis associated with primary sclerosing cholangitis. AB - OBJECTIVE: This study determined predictive factors for postoperative complications and outcome after ileal pouch-anal anastomosis in patients with ulcerative colitis and primary sclerosing cholangitis. SUMMARY BACKGROUND DATA: Patients with ulcerative colitis and primary sclerosing cholangitis treated by colectomy and ileostomy are at high risk of troublesome bleeding from peristomal varices. METHODS: Postoperative complications and outcome were assessed in 40 patients with ulcerative colitis and sclerosing cholangitis who received an ileal pouch-anal anastomosis between January 1981 and February 1990. RESULTS: Immediate postoperative and remote ileoanal anastomosis-related complications were high but related directly to the severity of liver disease. No patient had perianastomotic anal bleeding. CONCLUSIONS: In patients with both ulcerative colitis and primary sclerosing cholangitis, ileal pouch-anal anastomosis is safe and is not associated with perianastomotic bleeding. PMID- 8466306 TI - Early and long-term effects of colectomy and endorectal pullthrough on bile acid profile. AB - OBJECTIVE: Although total colectomy with mucosal proctectomy and endorectal pullthrough affects two sites critical to the enterohepatic circulation of bile acids, little information is available regarding the manner in which normal digestive physiology is altered by these procedures. This study defines the early and long-term effects of colectomy and endorectal pullthrough on bile acid profile and the long-term effects on biliary lipid metabolism. SUMMARY BACKGROUND DATA: Specific changes in bile acid absorption have been reported in patients after ileal resection. Recent studies from our laboratory indicate that in the early postoperative period, colectomy with endorectal pullthrough causes a significant decrease in gallbladder bile concentrations of total bile acids, cholesterol, phospholipids, and calcium. The observation by several authors that the pouch undergoes morphologic and perhaps functional adaptation suggest that these changes may be transient and perhaps reversible. METHODS: These studies were done in an awake, unanesthetized canine model that allows periodic sampling of gallbladder bile without creation of an external biliary fistula and its associated sequelae. Animals were ultimately randomly assigned to either laparotomy and gallbladder cannulation (N = 6), or gallbladder cannulation with total colectomy and ileorectal anastomosis (N = 7), or biliary cannulation, colectomy, mucosal proctectomy and endorectal pullthrough with ileal reservoir (N = 5). RESULTS: Six weeks after operation, colectomy and ileorectal anastomosis were associated with a significant alteration in the relative composition of bile acids in gallbladder bile. These early changes were manifested by a significant (p < 0.05) increase in taurocholic acid and a concomitant decrease in taurodeoxycholic acid. These changes became even more pronounced in the ileorectal anastomosis group 12 weeks after colectomy and ileorectostomy. Although similar changes in the relative concentrations of individual bile acids occurred in the 6-week endorectal animals, bile acid profile was restored to normal by 12 weeks. CONCLUSIONS: Colectomy with ileorectal anastomosis leads to early and significant changes in bile acid profile, which persist and become even more pronounced with time. In contrast, the construction of an ileal reservoir after colectomy facilitates restoration of a normal bile acid profile. We propose that these alterations in bile acid metabolism result from adaptation of the ileal reservoir as its mucosa assumes functional characteristics of normal colon. PMID- 8466307 TI - Nissen fundoplication for reflux esophagitis. Long-term clinical and endoscopic results in 109 of 127 consecutive patients. AB - OBJECTIVE: This study evaluates the clinical and endoscopic long-term results of Nissen fundoplication in reflux esophagitis. SUMMARY BACKGROUND DATA: Nissen fundoplication has been reported to give good results in the treatment of gastroesophageal reflux with success rates up to 78-97%. Most of the previous studies on long-term results of fundoplication have, however, been based on interviews with only sporadic endoscopic examinations. METHODS: Of 127 patients consecutively treated with Nissen fundoplication for reflux esophagitis, 109 were available for follow-up after a median of 77 months. Upper gastrointestinal endoscopy was done in 105 cases, and all the patients with reflux symptoms or abnormal endoscopic observations were referred to esophageal 24-hour pH monitoring and manometry. RESULTS: No symptoms of gastroesophageal reflux were reported by 73 of the 109 patients, but dysphagia was present in 47. Endoscopy showed defective fundic wrap in 24 patients. Objective evidence of reflux was found in 24 patients (endoscopic esophagitis in 18 and pathologic 24-hour pH score without esophagitis in 6). Esophagitis was found in 14 of the 24 patients with defective wrap, but in only 4 of the 81 with infact wrap. CONCLUSIONS: Nissen fundoplication alleviated symptoms of gastroesophageal reflux and cured esophagitis in great majority of cases. The main determinant of outcome was the state of the fundic wrap. PMID- 8466308 TI - Peptic ulcer surgery in patients with liver cirrhosis. AB - OBJECTIVE: This study identified risk factors of surgical treatment for gastroduodenal ulcer disease in patients with liver cirrhosis. SUMMARY BACKGROUND DATA: Liver cirrhosis is frequently associated with complicated peptic ulcer disease. Surgery in liver cirrhotics has a high mortality and morbidity especially when abdominal operations are performed. METHODS: Sixty-nine patients undergoing surgery for gastroduodenal ulcer disease between 1972 and 1991 were studied, retrospectively. RESULTS: Ninety percent of patients required emergency surgery for bleeding ulcer (n = 45) or perforation (n = 17). Mortality was 29% for elective patients (n = 7), 35% for patients with perforation and 64% for patients with bleeding. Overall mortality of 69 patients was 54%. Only 15 of 69 patients (22%) had an uncomplicated postoperative course. Postoperative bleeding, septic complications, and renal failure were the most frequent postoperative complications. Bleeding and multiple organ failure were the leading causes of death in 70% of patients. A univariate analysis determined preoperative hemoglobin < 12 g/L (p < 0.05), systolic blood pressure < 100 mm Hg (p < 0.025), prothrombin time < 60% (p < 0.05) and the presence of portal hypertension (p < 0.01) as prognostic factors. No significant correlation with survival could be established for excretory liver function (serum bilirubin) and partial thromboplastin time. CONCLUSIONS: To improve treatment results it is recommended (1) to substitute blood products (particularly coagulation factors) early and in sufficient quantities, (2) to diligently search for and to treat septic foci and administer antibiotics in a nonrestrictive manner, and (3) to restrict the operative procedure to the treatment required for control of the ulcer complication. PMID- 8466310 TI - Fetal wound healing. The ontogeny of scar formation in the non-human primate. AB - OBJECTIVE: This study determined how scar formation develops in a non-human primate model of fetal skin repair. SUMMARY BACKGROUND DATA: A transition from healing scarlessly to healing with scar formation characterizes skin repair in rat and sheep fetuses. New knowledge of the regulatory processes occurring in the fetal wound at the initial stages of scar formation may provide insights into the early mechanisms of scar formation. METHODS: Full-thickness wounds were made in fetal rhesus monkey lips from 75 through 114 days gestation (n = 6, term = 165 days). Wounds were harvested at 14 days postwounding and processed for histology (hematoxylin & eosin, Masson's trichrome) as well as immunohistochemistry (human type I or type III collagen). RESULTS: Wounds healed with complete restoration of normal tissue architecture in the 75-day gestation fetus. However in the 85-100 day gestation fetuses, wounds healed with an absence of hair follicles and sebaceous glands, but the dermal collagen pattern remained reticular and similar to that in unwounded dermis. At 107 days, a thin scar was present in the wound, thereby demonstrating a transition to scar formation between 100 and 107 days gestation (early 3rd trimester) in the non-human primate. CONCLUSIONS: In the non human primate fetus, a transition from scarless repair to adult-type repair with scar formation occurs in the early third trimester. These data provide insight into the transition process; the ontogeny of scar formation is characterized initially by wounds healing without the presence of epidermal appendages but with a normal reticular dermal collagen pattern, which we term the "transition wound." PMID- 8466309 TI - Carcinoid tumors of the appendix. AB - OBJECTIVE: A retrospective study of 41 patients with histologically confirmed diagnosis of appendix carcinoid tumors was undertaken by reviewing the surgical records at Massachusetts General Hospital. METHODS: There were 8 male and 33 female patients (mean age 32 years). Twenty-two patients (54%) presented with signs and symptoms suggestive of acute appendicitis. In 19 patients (46%) the lesions were discovered incidentally. The tumors were located in 32 patients at the tip, in 6 patients in the middle third, and in 3 patients at the base of the appendix. The tumor was less than 1 cm in diameter in 32 patients, between 1 and 2 cm in 7 patients, and was bigger than 2 cm in 2 patients. In 29 patients, the depth of tumor penetration was confined to the submucosa or to the muscle layers of the appendix, and in 8 patients the serosa was involved. In 4 patients, evidence of tumor extension into the meso-appendicular fat was present, including one patient with a tumor bigger than 2 cm and local lymph-node metastases. Forty patients underwent appendectomy alone. One patient with a tumor size bigger than 2 cm in diameter with positive lymph nodes in the mesoappendix underwent secondary right hemicolectomy. Complete follow-up was achieved in 35 patients, and all patients remained free of tumor recurrence. CONCLUSIONS: The authors conclude that appendiceal carcinoids are rare and most often are asymptomatic. Tumors of less than 1 cm are adequately managed by appendectomy alone. The appropriate treatment for tumors of 1 to 2 cm continues to be controversial. Right hemicolectomy is recommended for all tumors larger than 2 cm, whereas preference for an aggressive approach should be given in young patients. PMID- 8466311 TI - Collagen synthesis in intact skin is suppressed during wound healing. AB - OBJECTIVE: Simultaneous monitoring of total collagen synthesis as well as synthesis in intact skin and in the wound to verify the higher priority of wound healing after surgery. SUMMARY BACKGROUND DATA: Synthesis of acute phase proteins is stimulated by surgical trauma. At the same time, production of albumin is inhibited and there is a net catabolism of skeletal muscle proteins. Similarly, the authors have found a transient inhibition of total collagen synthesis after surgery. The authors hypothesized a lower priority in synthesis of structural and peripheral collagen for the benefit of wound healing. METHODS: The concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured in suction blister fluid of intact skin and in wound fluid in ten surgical patients. PICP and PIIINP concentrations in serum were also measured. Specific radioimmunoassays were used. RESULTS: In peripheral skin, the median preoperative concentrations of PICP and PIIINP were 228 and 140 micrograms/L, respectively. On postoperative days 1, 2, 4 and 7, the median concentration of PICP was 145 (p = 0.01, Wilcoxon signed rank sum test), 102 (0.02), 159 (0.03), and 152 (0.06) micrograms/L, respectively. The postoperative medians of PIIINP were 68 (p = 0.17), 76 (0.04), 66 (0.06), and 56 (0.03) micrograms/L, respectively. At the same time, collagen synthesis in the wound increased dramatically from the second day on. After an initial decrease, propeptide concentrations in serum gradually increased from the fourth day on. CONCLUSIONS: Collagen synthesis is regulated for the benefit of the wound during the acute phase response. PMID- 8466312 TI - Physiologic study of bile salt and lipid secretion in rats after liver transplantation. AB - OBJECTIVE: This experiment determined the effects of liver transplantation on bile salt kinetics and biliary lipid secretion. SUMMARY BACKGROUND DATA: Depression of bile secretion in the three main components and bile cholesterol supersaturation with a high incidence of cholesterol stone formation have been documented in patients with end stage liver diseases after transplantation. However, physiologic changes of bile salt and lipid secretion in recipients remain unclear. METHODS: The study was done using a rat liver transplant model with 1 and 6 hours of donor liver cold preservation in saline. A chronic common bile duct fistula and a duodenal cannula were established for bile collection and the sample biochemical study for 6 days. RESULTS: Altered bile salt kinetics in liver grafted rats included depressed bile flow for 1-3 hours after the revascularization, decreased bile salt concentration and outputs, reduced bile salt basal synthesis rate, and reduced bile salt pool size during the early postoperative period. Phospholipid concentration and secretion rate depressed for 1-3 days without altered cholesterol level. The uncoupling change of the cholesterol and the other bile components resulted in an increased lithogenic indices in bile on days 2 and 3. CONCLUSION: Alterations of bile composition and bile salt kinetics occur in liver transplanted rats. The changes may result from injuries of the liver microcirculation and parenchymal cells caused by cold preservation. The study of bile secretion is helpful for evaluation of the initial graft function. The changed ratio of three bile components may be important for cholesterol stone formation in the liver transplant recipient. PMID- 8466313 TI - Growth hormone after abdominal surgery attenuated forearm glutamine, alanine, 3 methylhistidine, and total amino acid efflux in patients receiving total parenteral nutrition. AB - OBJECTIVE: The study clarified the effects of growth hormone treatment on forearm amino acid efflux in patients with full nutritional support after gastrointestinal surgery. SUMMARY BACKGROUND DATA: Growth hormone attenuates net nitrogen loss after surgical trauma. An increase in net protein synthesis has been described, whereas the results regarding protein breakdown have been conflicting. METHODS: Elective patients undergoing abdominal surgery were double blindly randomized to treatment with recombinant human growth hormone (GH, n = 9) 24 IU or placebo (PL, n = 10) the first 5 postoperative days. All received parenteral nutrition (nitrogen = 5.7 +/- .1 g/m2, energy = 1018 +/- 12 kcal/m2 (125 +/- .7% of BMR) and epidural analgesia. Amino acid plasma levels and forearm fluxes were measured. RESULTS: The second postoperative day, growth hormone abolished forearm efflux of total amino acid nitrogen (GH: 170 +/- 117, PL: -785 +/- 192 nmol/100 mL/min, p = .0007) due to reduced losses of both essential and nonessential amino acids. Glutamine release was abolished (13 +/- 15 vs. -137 +/- 43 nmol/100 mL/min, p = .007) and alanine release attenuated (-61 +/- 17 vs. -211 +/- 51 nmol/100 mL/min, p = .01). 3-Methyl-histidine release was attenuated (-.20 +/- .11 vs. -.62 +/- .09 nmol/100 mL/min, p = .04). Growth hormone also induced decreased venous plasma amino acid levels. CONCLUSIONS: When given after gastrointestinal surgery in patients treated with total parenteral nutrition, growth hormone treatment abolished glutamine, 3-methylhistidine, and total amino acid nitrogen loss from forearm tissue. Alanine loss from forearm tissue was attenuated. PMID- 8466315 TI - Pseudocoarctation of the aorta presenting as a mediastinal mass with dysphagia. AB - Pseudocoarctation is an uncommon anomaly thought to be caused by congenital elongation and kinking of the aorta. We report a case of pseudocoarctation of the aorta presenting as a superior mediastinal mass causing dysphagia. Aortography and echocardiography revealed dilatation of the aorta and an aneurysm below the level of the pseudocoarctation. The patient underwent operative repair of the pseudocoarctation and associated aneurysm with good symptomatic relief. Review of the literature and experience with this case demonstrate that pseudocoarctation of the aorta cannot necessarily be regarded as a benign condition. Surgical treatment is recommended for all symptomatic patients and for those with associated aneurysm formation. PMID- 8466314 TI - Double-orifice mitral and tricuspid valves in association with the Raghib complex. AB - A 19-year-old woman presented clinically with a left to right pretricuspid shunt. Echocardiography revealed a large ostium primum defect and a double-orifice mitral valve. Operative findings revealed additionally a double-orifice tricuspid valve and a left superior vena cava draining to the roof of the left atrium. The atrioventricular valves were competent. The primum defect was patched and the left superior vena cava was rerouted. PMID- 8466316 TI - Successful resection of a recurrent leiomyosarcoma of the pulmonary trunk. AB - We successfully performed a total resection of the pulmonary artery trunk and replaced it with an equine pericardial xenograft roll in a patient with a recurrent leiomyosarcoma. We believe, based on anatomic and embryologic principles, total rather than partial resection of the pulmonary artery trunk should be the treatment of choice for primary leiomyosarcomas of the pulmonary artery. PMID- 8466317 TI - Systolic anterior motion of the mitral valve after mitral valve repair without a ring. AB - We report a case of systolic anterior motion of the mitral valve after mitral reconstruction without a semirigid mitral annular ring. A 56-year-old man with mitral regurgitation due to ruptured chordae tendineae underwent mitral valve reconstruction by replacement of chordae tendineae, leaflet excision, and suture annuloplasty without an annular ring. Postoperatively, left ventricular outflow tract obstruction developed and echocardiography revealed systolic anterior motion of the mitral valve. These findings disappeared after medication with a beta-blocking drug. PMID- 8466318 TI - Pyoderma gangrenosum after coronary artery bypass grafting. AB - Pyoderma gangrenosum is a rare cutaneous disorder that may complicate recovery after a cardiac operation. The lesions appear to represent a necrotizing infection; however, they do not respond to surgical debridement and antibiotic therapy. The treatment is based on high-dose corticosteroids and concomitant treatment of any underlying systemic disease. PMID- 8466319 TI - Technique of single-lung transplantation. AB - The technique of single-lung transplantation at our institution has evolved as our experience has increased over the past 3 1/2 years. This technique is described and illustrated. Surgical staples are used to perform recipient pneumonectomy and provide free access to the hilar structures for anastomoses. The modified, telescoped bronchial anastomosis allows healing while obviating the need for omentopexy as seen in our last 30 bronchial anastomoses. PMID- 8466320 TI - Pericardial patch repair of left ventricular aneurysm. AB - Infectious complications associated with the use of Teflon felt buttresses in left ventricular aneurysm repair may result in serious morbidity. Use of an autologous pericardial patch is an alternative approach that should be considered. The technique, which we have used in 4 patients, is described. PMID- 8466321 TI - New cardiac retractor for epicardial electrode insertion via subxiphoid approach. AB - A new retractor for the insertion of epicardial screw-in electrodes is described. We have found that this instrument can be easily applied to the heart and gives excellent exposure for electrode insertion. PMID- 8466322 TI - New technique for improving hemostasis in aortic root replacement with composite graft. AB - By using both aortic annular and supraannular aortic wall tandem suture lines, we have, in our experience, markedly improved hemostasis in aortic root replacement with composite conduits of two types. Using this technique, 4 of 5 patients required 2 units or less of transfused red blood cells. Two patients did not receive transfusions. The technique consists of using interrupted mattress sutures to anchor the lower part of the valve sewing ring to the aortic annulus. The upper part of the sewing ring is then anchored with a running suture line to the cut edge of the supraannular aortic wall. PMID- 8466323 TI - Total anomalous pulmonary connection: then and now. AB - In their classic article "Total anomalous pulmonary venous drainage. Correction with cardiopulmonary bypass in 62 patients," Denton A. Cooley, MD, and associates defined the proper course of therapy for most patients with this lesion. This article was published in 1966 in the Journal of Thoracic and Cardiovascular Surgery. The text and illustrations in this signal publication have served as one of the guiding features for surgeons attempting operations on patients with these lesions since that time. This article reviews that publication and points out the marked similarities between the treatment practices at that time and those in use today. PMID- 8466324 TI - 1980: descending aortic aneurysmectomy without adjuncts to avoid ischemia. 1993 update. AB - Encouraged by reports on the safety of simple aortic cross-clamping for resection of descending aortic aneurysm, we began utilizing this technique more liberally in 1976. This study was undertaken to examine the results of operation in 36 patients, equally divided into two distinct groups. In Group 1, either extracorporeal circulation or indwelling temporary shunts were employed during the period of aortic occlusion. In Group 2, simple aortic cross-clamping was utilized to manage the lesion. No adjuncts were used to avoid ischemia in the latter group. The only 2 early deaths and two instances of paraplegia occurred in Group 1. In general, there were fewer complications in Group 2, with approximately two-thirds of the patients experiencing an uneventful postoperative course. These differences are considered important since the two groups were similar in respect to the extent and nature of the lesions and other factors contributing to operative risk. PMID- 8466325 TI - Bronchopleural fistula. PMID- 8466326 TI - AIDS-related bronchopleural fistula. PMID- 8466327 TI - Retrograde versus antegrade cardioplegia: impact on right ventricular function. PMID- 8466328 TI - Surveillance of Barrett's esophagus. PMID- 8466329 TI - Cavernous hemangioma of the intercostal space. PMID- 8466330 TI - Bentall redo. PMID- 8466331 TI - Treatment of acute aortic arch dissection. PMID- 8466332 TI - The vascular endothelium: friend or foe? PMID- 8466333 TI - Deep hypothermic arrest and left thoracotomy for repair of difficult thoracic aneurysms. AB - Seven patients with complex thoracic aortic aneurysms were operated on using profound hypothermia and circulatory arrest through a left thoracotomy. Three patients had false aneurysms, 2 had large aneurysms precluding access for proximal control, 1 patient had had previous hemiarch replacement, and 1 patient had a thoracoabdominal aneurysm. All patients were cooled on partial cardiopulmonary bypass until the electroencephalogram was isoelectric (approximately 15 degrees C rectal temperature). Circulatory arrest times ranged from 7 to 56 minutes (median, 34 minutes). There was one death due to cardiac failure, and paraplegia developed in 1 patient. The 6 survivors are otherwise well at a median of 12 months postoperatively. Hypothermia and circulatory arrest is an invaluable technique for the treatment of complex aortic aneurysms requiring left thoracotomy for resection. The techniques employed are described and the indications for their use are discussed. PMID- 8466334 TI - Myocardial performance after contusion with concurrent hypovolemia. AB - Myocardial contusion may present as a benign nonclinical event or a life threatening emergency. Although cardiac output is recognized to be decreased with major contusion, the contribution of hypovolemic shock to myocardial dysfunction is unclear. This study was designed to evaluate the relationship between myocardial contusion and hypovolemic shock. After Sprague-Dawley rats were anesthetized, contusions were administered at either 80 psi or 120 psi. Half of each group then underwent hypovolemic shock. After 24 hours of recovery, cardiac hemodynamics were studied in each subgroup using the Neely-Langendorff apparatus. Isoenzymes and histology were evaluated as well. The data showed that rats undergoing hypovolemic shock in each subgroup had a significant decrease in cardiac output when compared with their controls. This decrease was more pronounced in the 120-psi group. Cardiac isoenzyme levels were elevated in all groups. Microscopic evaluations showed contusion in the controls and necrosis in the shock groups. Patients whose injuries are compatible with myocardial contusion and hypovolemic shock should be resuscitated quickly and evaluated for myocardial dysfunction secondary to infarction. PMID- 8466335 TI - Sternal resection and reconstruction. AB - Twenty-one patients underwent sternal resection and reconstruction. Surgical indications included sternal infection in 9 patients, recurrent breast cancer in 6, metastatic carcinoma from an unknown primary in 2, pectus excavatum in 2, and osteogenic sarcoma and eosinophilic granuloma in 1 each. Management included partial sternectomy in 10 patients (group 1) and complete sternectomy in 11 (group 2). Chest wall reconstruction was by various flaps and mesh repairs. Blood transfusions averaged 2 units in group 1 versus 5.5 units in group 2 (p = 0.02). Average number of days until extubation was 2.6 in group 1 versus 7.3 in group 2 (p = 0.04). Average number of intensive care unit days was 4.4 for group 1 versus 9.4 for group 2 (p = 0.03). The number of days until discharge was 14 days for group 1 versus 20 days for group 2. Complications occurred in 40% of group 1 and 82% of group 2 patients. Overall mortality was 9.5%. Sternal resection and reconstruction, particularly complete sternal resections, are a major undertaking with substantial morbidity. Using a multidisciplinary approach (cardiothoracic, plastic and reconstructive, critical care medicine, and infectious disease) and aggressive pulmonary support, acceptable cosmetic and functional results are possible. PMID- 8466336 TI - Surgical management of pulmonary infections in chronic granulomatous disease of childhood. AB - Chronic granulomatous disease of childhood is an inheritable disorder of phagocytic cell respiratory burst resulting in recurrent, life-threatening, catalase-positive infections. The lung is the most common site of infection, and pulmonary disease is the primary cause of death in greater than 50% of children with chronic granulomatous disease. Still, the role of surgery in management of this disease remains undefined. Between 1974 and 1990, 19 patients with chronic granulomatous disease required 31 thoracic interventions at our institution. Patients ranged in age from 2.5 to 27 years (mean age, 15 years). Seventeen of 19 patients (89%) had had previous pulmonary infections. Patients presented as toxic (temperature > 38.5 degrees C, chest pain, and cough) in 22 instances before the 31 procedures. Aggressive surgical intervention for diagnosis and extirpation of localized infections was undertaken with lobectomy/pneumonectomy with or without other procedures (5), bisegmentectomy (2), segmentectomy with or without other procedures (5), or wedge with or without other procedures (13). In five instances, an empyema was drained; a chest tube for a sterile collection was placed in one instance. There was one intraoperative death, and 3 patients died 22 to 600 days postoperatively with overwhelming sepsis. The mean hospitalization was 101 days (range, 24 to 600 days). Wound complications occurred in 5 patients, requiring 17 separate anesthetic debridements. A change in therapy was dictated by the results of the procedure in 23 of 31 instances (74%). Thoracic surgeons must be aware of this rare cause of immunosuppression in these children and, due to the unusual nature of the pulmonary infections, should follow an aggressive approach in their diagnosis and management. PMID- 8466337 TI - Pulmonary artery sleeve resection for abutting left upper lobe lesions. AB - Because the left upper lobe bronchus overlies the left pulmonary artery (PA), T2 3 lesions, N0-1 disease, or rarely inflammation may involve this vessel, necessitating lobectomy with partial PA resection or pneumonectomy with sacrifice of the lower lobe. In 486 operations performed for left upper lobe lesions between 1966 and 1992 (wedge, 111; segmentectomy, 131; lobectomy, 155; pneumonectomy, 89), isolated PA encroachment was caused by bronchogenic carcinoma (32), invasive aspergillosis (2), or organized pneumonitis (1) and occurred in 9% (32/360) of malignant left upper lobe tumors and 2% (3/126) of benign lesions. Initially (1966 through 1979), PA involvement was the indication for 30% (18/60) of left pneumonectomies. Later (1980 through 1990), tangential resection of the PA was attempted in 11, 5 ending up with pneumonectomy. Overall, 35 of 244 patients undergoing major left upper lobe resection (lobectomy or pneumonectomy) had PA encroachment. Recently, we have performed, selectively in patients with restricted lung function, six left upper lobectomies with sleeve resection of the PA. Paneled saphenous vein interposition was used (3) or 18-mm polytetrafluorethylene tube prostheses (3). All patients survived, 1 later requiring completion pneumonectomy for bronchostenosis after wedge bronchoplasty. Two have since died of metastases or pulmonary insufficiency; the remainder (average follow-up, 17 months) are asymptomatic with lower lobe function in 3 confirmed by differential ventilation-perfusion scans and pulmonary angiography. PMID- 8466338 TI - Allograft replacement of the aortic valve versus the miniroot and valve. AB - Between February 1986 and April 1992, 27 patients ranging in age from 8 to 65 years (median, 18 years) underwent allograft replacement of the aortic valve with one death (operative mortality, 3.7%). The indications for operation were aortic regurgitation in 14 patients, aortic stenosis in 7, aortic stenosis/regurgitation in 4, and endocarditis in 2. Associated lesions included annuloectasia in 4 patients (1 with Marfan's syndrome), sinus of Valsalva aneurysm in 3, coronary artery disease in 4, and ventricular septal defect in 2. The freehand technique was used in 12 patients and the miniroot replacement in 15 patients. The postoperative transvalvular gradient was 17 mm Hg in freehand valves and 7 mm Hg in the miniroot valves. Initial postoperative study showed no or trivial aortic regurgitation in all 26 survivors except 1 freehand patient who had mild aortic regurgitation. At late study up to 6 years postoperatively all 10 of our available freehand patients showed progressive regurgitation, and it was severe in 4 patients. By contrast only half of the miniroot patients showed progressive regurgitation, and in none was it severe. Allograft replacement of the aortic valve can be done in children and adults with low mortality rate, short hospital stay, and excellent early function. Subsequent follow-up studies suggest that the miniroot replacements are superior to the freehand valves with lower transvalvular gradients, less valvular regurgitation, and delayed progression of valvular regurgitation. PMID- 8466339 TI - Mitral valve repair using a flexible and adjustable annuloplasty ring. AB - Initial experience with a new flexible and adjustable mitral annuloplasty ring is described. Used in conjunction with standard techniques of mitral valve repair, this ring was implanted in 21 consecutive patients undergoing elective operation for mitral regurgitation. Satisfactory valve repair was feasible in 20 of these patients. Once the ring was sewn in place, adjustment of the ring to reduce or eliminate residual regurgitation was beneficial in 9 patients. Excellent results were achieved as determined by intraoperative transesophageal echocardiography. Comparable late results were found in all but 1 patient up to 1 year after repair. This patient required mitral valve replacement 6 months after repair due to failure of papillary muscle reconstruction. The BiFlex ring has the merits of a flexible prosthesis with the advantage of easy adjustment once secured in place. PMID- 8466340 TI - Replacement of the transverse aortic arch for type A acute aortic dissection. AB - Surgical treatment of acute aortic dissection involving the segment of transverse aortic arch is difficult and often associated with a high mortality and morbidity. The high mortality and morbidity are primarily related to anatomic features and techniques of cerebral protection employed during the period of aortic branch occlusion needed for reconstruction. This study reports our experience of 20 consecutive cases of acute type A aortic dissection treated by repair or replacement of the transverse aortic arch during emergency operation. Ages of the patients ranged from 56 to 76 years. All patients were referred to us within 2 weeks of onset (mean time, 58 hours). Selective cerebral perfusion or deep hypothermia with complete circulatory arrest was employed during the period of aortic branch occlusion. Duration of cerebral perfusion, circulatory arrest, myocardial ischemia, and cardiopulmonary bypass averaged 106 minutes, 32 minutes, 127 minutes, and 248 minutes, respectively. There were three operative deaths. All three dissections were ruptured ones, and the patients died of hemorrhage, deep coma, or multiple organ failure. One patient died of infection 3 months after operation. The remaining patients are alive and well without any detectable neurological deficit 1 month to 4 years postoperatively. This experience emphasizes that repair or replacement of acute type A aortic dissection involving the aortic arch can be performed safely by adequate selection of patients, supportive measures, and operative methods. PMID- 8466341 TI - Tracheoesophageal fistulas. AB - Tracheoesophageal fistula is an uncommon clinical problem, and can be either congenital or acquired in origin. In this report, we present our experience in the management of 41 patients with tracheoesophageal fistula (28 male, 13 female; age ranging from 8 to 69 years) who were seen during the period spanning 1968 to 1989 at the National Research Center of Surgery, Moscow. During this time frame fewer malignant and correspondingly more posttraumatic and postoperative fistulas were observed. The most common clinical findings were cough associated with eating, production of sputum mixed with food, and weight loss with profound weakness. In the vast majority of patients, diagnosis was made using radiologic contrast studies, with endoscopic assessment being occasionally necessary. We classify our surgical approaches as "radical" (the isolation and ablation of the communication), "conditionally radical" (implying creation of a neoesophagus or thoracoplasty with muscle flap obliteration of the fistula and associated chronic empyema cavity), or "palliative" (usually entailing gastrostomy alone). Of the 32 patients undergoing surgical treatment in this series, 21 underwent radical or conditionally radical procedures; there was no operative mortality, and long-term follow-up shows that 19 of the 20 long-term survivors report satisfactory, good, or excellent status. This report summarizes the indications, timing, technique, and results of the various surgical approaches, and also delineates measures for the prevention of postoperative tracheoesophageal fistula. PMID- 8466342 TI - High-risk cardiac operation: a viable alternative to heart transplantation. AB - To determine if high-risk heart operation with circulatory support standby is an acceptable alternative to direct heart transplantation, we reviewed 21 patients who were accepted as heart transplant candidates but offered a heart operation because of the availability of circulatory support. Preoperative left ventricular ejection fraction was 0.25 +/- 0.08 (mean +/- standard deviation), and New York Heart Association functional class was 3.4 +/- 0.7. The patients underwent 16 bypass graft operations, 4 mitral and 2 aortic valve replacements, and 4 defibrillator implantations (combined procedures in 5 patients). An intraaortic balloon pump was placed in 12 patients. One patient required biventricular assist device support but was weaned in 11 days. Twenty patients were discharged 14.8 +/ 11.5 days postoperatively. One patient died 15 days postoperatively of amiodarone-induced respiratory failure, and 1 died suddenly 2 months postoperatively. At 10.5 +/- 6 months postoperatively, 19 patients (90%) are alive. Mean functional class is 1.9 +/- 0.9. None of the patients has undergone transplantation, but 2 are awaiting donor organs. We conclude that in selected heart transplant candidates high-risk heart operation is a viable alternative to direct heart transplantation. PMID- 8466343 TI - Exercise coronary flow reserve of bilateral internal thoracic artery bypass grafts. AB - We attempted to quantify the exercise coronary flow reserve in 20 patients with bilateral internal thoracic artery grafts to the left coronary arteries (group I) who had complete revascularization. The coronary sinus blood flow was measured by the continuous thermodilution method both at rest and during exercise (50 W for 8 to 9 minutes) approximately 1 month after the operation. These results were compared with 30 patients treated with an internal thoracic artery and saphenous vein grafts to the left coronary arteries (group II) and 9 patients with saphenous vein grafts alone to the left coronary arteries (group III). There were no differences among the three groups in age, sex, number of vessels involved, heart rate, double products, left ventricular (LV) end-diastolic pressure, LV ejection fraction, LV end-diastolic volume, or LV mass at the time of study. None of the 59 patients in the study had abnormally enlarged LV end-diastolic volume or increased LV mass. The postoperative coronary sinus blood flow per 100 grams of LV mass at rest was similar among the three groups (73.0 +/- 28.4 mL/min per 100 g LV mass in group I, 73.4 +/- 31.1 mL/min per 100 g LV mass in group II, and 75.9 +/- 28.5 mL/min per 100 g LV mass in group III [not significant]) and significantly (p < 0.01) increased by exercise, although the differences between groups during exercise were not significant (158.9 +/- 45.9, 153.5 +/- 72.1, and 148.3 +/- 60.0 mL/min per 100 g LV mass, respectively [not significant]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466344 TI - Long-term complications of implantable cardioverter defibrillator lead systems. AB - Over a period of 8.5 years in 255 patients with full-system implantable cardioverter defibrillators, lead-specific complications requiring reoperation developed in 32 patients. A total of 36 leads were affected. Lead fracture was the cause of failure in half of these patients. Refinement and improvement in structural designs of these leads, use of endocardial leads, and attention to technical details during implantation should decrease the incidence of these complications. PMID- 8466345 TI - Effects of cardiomyoplasty on biventricular function in canine chronic heart failure. AB - Dynamic cardiomyoplasty, the use of skeletal muscle to assist the heart, is a new therapy for the treatment of heart failure. However, the effects of cardiomyoplasty on biventricular function and the synchrony of ventricular contraction are not fully known. We assessed the efficacy of latissimus dorsi muscle (LDM) dynamic cardiomyoplasty in a chronic model of biventricular failure. Five dogs received doxorubicin (1 mg.kg-1.wk-1) for up to 12 weeks to induce heart failure and then underwent a biventricular cardiomyoplasty. After operation, the muscle was progressively stimulated according to an established protocol. When training was complete (10 weeks), radionuclide ventriculographic and catheterization data were obtained. Peak left ventricular (LV) systolic pressure and its first derivative were unchanged, whereas LV end-diastolic pressure decreased slightly with LDM assistance (11.0 +/- 1.6 to 9.6 +/- 1.5 mm Hg; p < 0.05). Right ventricular (RV) systolic pressure increased significantly with LDM assistance from 21 +/- 2 to 26 +/- 3 mm Hg (p < 0.05), whereas its first derivative and RV end-diastolic pressure were unchanged. Dynamic cardiomyoplasty significantly improved LV ejection fraction from 0.18 +/- 0.07 without LDM assistance to 0.31 +/- 0.05 with LDM assistance (p < 0.05); similarly RV ejection fraction increased from 0.32 +/- 0.07 to 0.45 +/- 0.06 with LDM assistance (p < 0.05). The temporal sequence of LV wall motion was assessed by phase analysis of the radionuclide ventriculograms. With skeletal muscle assistance, standard deviation ("spread") decreased from 31.6 +/- 17.4 to 20.0 +/- 15.4 degrees (p < 0.06), whereas skewness ("symmetry") was unchanged. Dynamic cardiomyoplasty improved both LV and RV ejection fractions without increasing diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466346 TI - Improvement of cardiac function impaired by repeated ischemic arrests in isolated rat hearts. AB - We investigated the effects of coenzyme Q10 and verapamil, either alone or in combination, on cardiac function impaired by repeated ischemic arrests and reperfusion in the isolated rat heart. In the group with a single ischemic arrest, the aortic flow, cardiac output, stroke volume, coronary flow, and heart rate recovered well (72% to 100% of the prearrest values). In the repeated-arrest group, the recovery of aortic flow (24%), cardiac output (30%), stroke volume (40%), or coronary flow (63%) was much poorer than that in the single-arrest group. Pretreatment with coenzyme Q10 given intraperitoneally improved aortic flow, cardiac output, stroke volume, coronary flow, and heart rate. The addition of verapamil to the reperfusion solution also protected the cardiac function with a decrease in heart rate. However, combination therapy with coenzyme Q10 and verapamil further increased the recoveries of aortic flow, cardiac output, stroke volume, and coronary flow to 57%, 61%, 77%, and 84%, respectively, which were better than the values after treatment with coenzyme Q10 or verapamil alone. We, therefore, suggest that treatment with coenzyme Q10 or verapamil, alone or in combination, in addition to St. Thomas' Hospital solution effectively protects cardiac function impaired by repeated ischemic arrests and reperfusion. PMID- 8466347 TI - A model to predict survival at time of postcardiotomy intraaortic balloon pump insertion. AB - To facilitate timely application of new forms of cardiac support to patients at highest risk after cardiotomy despite conventional support with the intraaortic balloon pump, an accurate prediction of survival must be available at the time of weaning from cardiopulmonary bypass. We, therefore, acquired 240 demographic, disease, and perioperative characteristics of 322 patients (mortality rate, 48.4%) who required IABP support to separate from bypass. Four variables available before or within 10 minutes of the first attempt at weaning from bypass significantly predicted mortality by stepwise logistic regression: complete heart block as demonstrated by need for temporary pacing at weaning (p < 0.001), advanced age (p < 0.002), preoperative blood urea nitrogen concentration (p = 0.036), and female sex (p = 0.048). An equation generated by the logistic model predicted a 72.2% survival rate in the 25% of patients at least risk (actual survival rate, 71.6%); in the 25% at greatest risk, death was predicted in 73.0%, and the actual mortality rate was 74.1%. The equation was then prospectively applied to 330 intraaortic balloon pump-supported patients managed at another institution. The overall mortality rate there was 41.2%; in the 25% at least risk, predicted survival rate was 70.5% (actual survival rate, 77.1%), and in the 25% at greatest risk, predicted mortality rate was 75.7% (actual mortality rate, 62.7%). Thus, retrospectively at one institution and prospectively at another, the equation generated by this model based only on data available at the time of weaning from bypass was able to define one subgroup of patients 2.6 to 2.7 times as likely to die as another subgroup from within similar cohorts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466348 TI - Balloon aortic valvuloplasty as a bridge to aortic valve replacement in critically ill patients. AB - This report highlights our experience in 5 patients with severe aortic stenosis and multiple organ failure undergoing balloon aortic valvuloplasty as a bridge to conventional aortic valve replacement. Balloon aortic valvuloplasty successfully stabilized the condition of these patients, improved organ function, and decreased their baseline risk profile. Elective aortic valve replacement was then performed without complications. Short-term palliation with balloon aortic valvuloplasty should be considered as a bridge to aortic valve replacement in selected patients with critical aortic stenosis and multiple organ failure. PMID- 8466349 TI - Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. AB - Cardiopulmonary bypass generates a systemic inflammatory response including the activation of the complement cascade and leukocytes contributing to postoperative morbidity. To evaluate whether the use of heparin-coated extracorporeal circuits could reduce these activation processes, we performed a study on 30 patients undergoing coronary artery bypass grafting who were randomly perfused with a heparin-coated circuit (Duraflo II, n = 15) or with a similar noncoated circuit (control, n = 15). Standardized systemic heparinization was applied for every patient before cardiopulmonary bypass. The use of heparin-coated circuits resulted in a reduction of systemic leukocyte activation during cardiopulmonary bypass reflected by reduced elastase release (p < 0.05) and tumor necrosis factor generation (p < 0.05) manifest after release of the aortic cross-clamp. In addition, blood samples taken from both the right and left atria after reperfusion revealed that the elastase release from the pulmonary microcirculation was absent in the Duraflo II group in contrast to the control group (p < 0.05). The pattern of complement activation, likely initiating this inflammatory reaction, was modified by heparin coating in two different aspects. There was a significant reduction of C3a generation after protamine administration in patients perfused with heparin-coated circuits, and there was a decrease of complement hemolytic capacity in pooled human serum incubated with heparin-coated tubing. These observations suggest that heparin coating might bind some of the complement components from the classic pathway, thereby reducing the inflammatory response to cardiopulmonary bypass. PMID- 8466350 TI - Effect of vascular clamp on endothelial integrity of the internal mammary artery. AB - The preservation of endothelial integrity is essential for maintaining patency of vascular grafts. The internal mammary artery flow is often interrupted with the application of a soft vascular clamp to achieve a bloodless field during the anastomosis. We investigated the effect of the vascular clamp on the internal mammary artery endothelium using the scanning electron and light microscope. The endothelium was examined before and at 15 and 30 minutes after clamping in both the pedicled and the skeletonized arteries. Endothelial integrity was breached by clamping with early evidence of platelet adhesion to the damaged areas. The severity of the endothelial damage was related to the clamp time, but there was no difference in the degree of damage between the pedicled and the skeletonized arteries. We conclude that the vascular clamp causes injury to the internal mammary artery endothelium and may be implicated in early postoperative graft failure. PMID- 8466351 TI - Operative creation of left to right cardiac shunts: pulmonary functional sequelae. AB - The creation of left to right cardiac shunts in neonates is frequently complicated by pulmonary morbidity in the immediate postoperative course. To elucidate the pattern, severity, and cause of lung dysfunction, pulmonary function testing was performed preoperatively and 1, 3, and 7 days postoperatively on 7 neonates undergoing Blalock-Taussig shunting. Pulmonary mechanics (compliance, conductance) were determined with esophageal manometry and pneumotachography, and functional residual capacity was measured by the helium dilution technique. The infants had pulmonary function preoperatively that was similar to that of healthy term neonatal controls. Significant decreases in compliance, conductance, and functional residual capacity were found on the first postoperative day (57%, 21%, and 53% of predicted, respectively). Alterations in conductance were more severe than those in compliance, but both were low through postoperative day 3. Functional residual capacity was the least affected parameter and recovered by postoperative day 3. All parameters were normal by postoperative day 7. These data indicate that shunting is associated with pulmonary morbidity through the third postoperative day that affects the airways more than the lung parenchyma. Pulmonary function studies of these infants may clarify the etiology of pulmonary dysfunction and have an impact on therapeutic strategies used in neonates undergoing cardiac operations. PMID- 8466352 TI - Systolic and diastolic function of both ventricles after prolonged cardioplegic arrest. AB - The current technique of donor heart preservation for transplantation is known to cause myocardial dysfunction. We have investigated the effect of 2, 4, and 8 hours of global ischemia at 4 degrees C with a single infusion of St. Thomas' Hospital cardioplegic solution on the recovery of right and left ventricular function in the blood-perfused, isolated pig heart. Two hours of ischemia caused significant deterioration in both left (p < 0.05) and right (p < 0.01) ventricular diastolic function as assessed by ventricular compliance and stiffness (reduction in left and right ventricular compliances, 19.3% +/- 14.8% and 13.3% +/- 3.5%, respectively) but had no significant effect on systolic function as evaluated by the slope value of the systolic pressure-volume relationship (peak elastance). Four hours of ischemia resulted in further reduction in ventricular compliance (left ventricle, p < 0.001; right ventricle, p < 0.05) and also caused left ventricular systolic dysfunction (p < 0.05). Eight hours of ischemia caused approximately 50% reduction in left ventricular (p < 0.01) and right ventricular (p < 0.05) compliance and left ventricular elastance (p < 0.001). Coronary vascular resistance at the end of 2 hours of reperfusion after preservation was significantly elevated as compared with the control value in all three groups. There was no correlation between the percentage increase in coronary vascular resistance and the percentage reduction in left or right ventricular diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466353 TI - Impairment of vascular endothelial function by high-potassium storage solutions. AB - High-potassium cold storage solutions are currently used to preserve myocardial function during heart transplantation. However, the effects of high potassium concentration on vascular endothelial function are not well known. We therefore tested vascular rings for endothelial-dependent and endothelial-independent relaxation during storage in normokalemic, normothermic buffers and then in buffers supplemented with 10 to 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced at all high potassium concentrations. Endothelial-independent relaxation was impaired only with 80 and 110 mmol/L KCl buffers. Both endothelial-dependent relaxation and endothelial-independent relaxation returned to normal values after washout of excess potassium. Similarly, endothelial-dependent relaxation and endothelial-independent relaxation were assessed in rings after 24 hours of hypothermic storage in normokalemic Krebs buffer, and in buffers containing 20 and 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced after preservation in the high-potassium solutions, whereas endothelial-independent relaxation was not impaired. We conclude that there is significant impairment of endothelial function after cold storage in a high-potassium buffer. Inadequate washout of potassium during normothermic conditions may lead to further functional impairment of vascular responsiveness. A low-potassium storage medium is recommended for improved vascular protection. PMID- 8466354 TI - New experimental technique to study blood cardioplegia in the isolated, perfused rat heart. AB - Blood cardioplegia has been extensively studied clinically and in the large animal experimental model. We describe here a modification of the original Langendorff technique to study continuous warm blood cardioplegia in the isolated, perfused rat heart. The excised heart is mounted on the perfusion apparatus and perfused with Krebs-Henseleit buffer. Prearrest hemodynamics are recorded. The shed blood in the mediastinal cavity (8 to 12 mL) is collected, filtered, and reconstituted into cardioplegic solution (hematocrit, 0.20; K+, 15 mmol/L). Hearts are arrested and maintained at 37 degrees C by continuous recirculation of blood cardioplegia for 1 hour. The blood cardioplegia system consists of a Silastic tubing oxygenator, peristaltic pump, and two filters (40 microns pore size). The heart is reperfused with Krebs-Henseleit solution, and postarrest hemodynamics are recorded. Percentage recovery of peak left ventricular pressure, heart rate, and coronary flow were 98.5 +/- 3.1, 102 +/- 4.2, and 98.5 +/- 4.5 (mean +/- standard error of the mean; n = 6), respectively. Myocardial oxygen consumption during arrest was 57 microL.min-1.g-1 dry wt, which is 10% of the myocardial oxygen consumption of a beating heart in in-vivo and ex vivo models. These results suggest the feasibility of studying blood cardioplegia in the isolated, perfused rat heart model under controlled conditions. Continuous warm blood cardioplegic arrest provided excellent myocardial protection for 1 hour in this model. PMID- 8466355 TI - Trans-ventricular septal defect approach for resection of accessory mitral valve tissue. AB - Accessory mitral valve tissue is a rare cause of left ventricular outflow tract obstruction, which can be difficult to recognize. Surgical resection by the conventional transaortic approach with or without left atriotomy is extremely difficult in infants with a small aorta. When a ventricular septal defect is present, it may be the best way to approach the accessory mitral valve tissue, because the ventricular septal defect is located just in front of it. Five infants underwent resection of accessory mitral valve tissue together with repair of other intracardiac malformations. In 3 infants, resection of accessory mitral valve tissue was easily performed through the ventricular septal defect, which required enlargement in 2 patients. PMID- 8466356 TI - Perfluorochemical reperfusion yields improved myocardial recovery after global ischemia. AB - Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p < 0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466357 TI - Aortic arch thrombosis in the neonate. AB - Two cases of neonatal aortic arch thrombosis are reported. One patient, who had ascending aortic thrombosis, died preoperatively. The other had reoperation and is alive and well at 6 months' follow-up. No obvious cause was found. PMID- 8466358 TI - Isolated bilateral ostial coronary artery stenoses. AB - Isolated coronary ostial narrowing is rare and most often attributed to atherosclerotic disease of the aorta. A man with isolated, bilateral stenoses of the coronary ostia is presented, who also had severe peripheral vascular disease. A review of previous reports concerning coronary ostial disease is presented. PMID- 8466359 TI - Successful surgical management of an aortic arch aneurysm with acute aorto pulmonary fistula. AB - Aortic arch aneurysm with acute aorto-pulmonary fistula is usually a postmortem diagnosis. Few reports of successful surgical management are noted. Despite the many advances in cardiac surgery over the last 30 years, the observed mortality rate for surgical correction has been very high. Early diagnosis and prompt surgical intervention using profound hypothermia and total circulatory arrest are essential to successful outcome. PMID- 8466360 TI - Pulmonary lymphangiomyomatosis causing bilateral pneumothorax during pregnancy. AB - A 32-year-old woman, 12 weeks pregnant, presented with bilateral spontaneous pneumothorax that did not heal with tube thoracostomy. At right and left thoracotomy, lymphangiomyomatosis of the lung was found and treated by pleurodesis. Lymphangiomyomatosis has been infrequently reported in the surgical literature, even though it may befall the thoracic surgeon to establish the diagnosis and aid in treatment. PMID- 8466361 TI - [An analysis of the antihypertensive properties of 3-nitropropionic acid, a compound from plants in the genus Astragalus]. AB - 3-Nitropropionic acid (NPA), a compound obtained from Astragalus species, elicited a dose-dependent relaxation of precontracted rabbit aortic rings. The remotion of endothelium or the presence of atropine, propranolol or brompheniramine did not modify the vasodilator effect of NPA but methylene blue clearly inhibited it. On the other hand the acute i.v. administration of NPA in normotensive rats or the chronic oral administration of NPA in renal hypertensive dogs, provoked both a decrease in blood pressure and bradycardia. Finally, NPA elicited negative inotropic and chronotropic effects in guinea pig isolated auricles, which were not blocked by atropine and it inhibited the increase in contractile force and heart rate elicited by isoproterenol. The present results indicate that NPA has vasodilator and antihypertensive properties. The arterial relaxation elicited by NPA was inhibited with methylene blue suggesting that it is a consequence of guanylate cyclase stimulation. The hypotensive effect was independent of the animal species or route of administration used. The bradycardia seen in rats and dogs and the negative chronotropic and inotropic effects observed in isolated auricles suggest that the hypotensive effect of NPA is a mixture of vasodilator and cardiodepressor actions. NPA cardiac effects may be related with inhibition of beta-adrenergic mediated responses. PMID- 8466362 TI - [A comparative study between surgical section and radiofrequency ablation of the anomalous pathways in the WPW syndrome]. AB - Radiofrequency catheter ablation is an effective alternative to medical therapy to patient with Wolff Parkinson White syndrome (WPW). The purpose of this study is to compare our results in 70 patients with WPW that underwent either surgery or ablation procedure with radiofrequency energy. Of this number of patients the surgical procedure was successful in 82%; complications were present in 15% and mortality in 8%. Average hospitalization was 6 to 10 days and cost from 2 to 10 thousand of new pesos. On the other hand, of 44 patients that underwent radiofrequency ablation, in 80% the procedure was finally successful with recurrence of 9% and no mortality. The hospitalization period was one day, the cost run from 500 to 2 thousand of new pesos in our institution. These results demonstrate the efficacy of the radiofrequency energy ablation in the treatment of WPW. This procedure is safe and less expensive than surgery. PMID- 8466363 TI - [The radiofrequency ablation of accessory pathways. The initial experience in Mexico]. AB - Thirteen patients with paroxysmal supraventricular tachycardia (SVT) due to an accessory pathway were submitted to an electrophysiological study and radiofrequency ablation of the Kent bundle. There were 9 males and 4 females. The mean age was 22 years. Other than their SVT, none had any structural heart disease. Ten of them had Wolff-Parkinson-White syndrome, and three had concealed accessory pathways. Two different types of radiofrequency devices were used: one generating damped sinusoid waves, and two other generators producing pure continuous sinusoid waves. With the first type, two attempts were made: one patient with a concealed pathway and one with overt preexcitation. The successful ablation was not achieved because this wave type is 100 times more powerful, it desiccates the tissue, and thus does not produce the right kind of lesion. The other eleven patients were divided in three groups: I) With left overt preexcitation (7 pts) II) Concealed left Kent bundles (2 pts) III) Right Kent bundles. Ablation was 100% successful in group I, while in the other two groups, only one patient of each was successfully ablated. The overall successful rate of these 3 groups was 81.8%. Of the two patients that could not be treated, one had an anterior septal Kent bundle and the other had a concealed left Kent bundle. We believe that catheter ablation is a very promising therapeutic procedure for patients with SVT, besides being a extraordinary instrument that will enable us to be able to understand further clinical electrophysiology. PMID- 8466364 TI - [The radiofrequency and the elimination of accessory atrioventricular pathways. The factors related to successful transcatheter ablation]. AB - Some factors related with successful radiofrequency catheter ablation were retrospectively analyzed from the initial patients with WPW syndrome that underwent this therapy. They were 21 patients, and success rate with radiofrequency therapy was 73%. Conventional conduction intervals were obtained from catheter ablation electrograms. Only ventricular activation around Delta wave onset, and earliest retrograde atrial activation were statistically significant for successful ablation (P < 0.05 both). Inadvertent interruption of AV-His bundle was produced ablating a septal accessory pathway, and no mortality procedure-related was observed. We conclude that radiofrequency catheter ablation of accessory pathways represents nowadays, an effective solution in patients with symptomatic arrhythmias, besides its high success rate and low risks, but different mapping criteria should be considered to attain an efficient elimination of atrioventricular accessory-pathways. PMID- 8466365 TI - [The radiofrequency ablation of accessory pathways in 100 consecutive patients with supraventricular tachycardias]. AB - The purpose of this study is to describe the results and the complications of radiofrequency catheter ablation, of accessory pathways in 100 consecutive patients. We had one patient with two pathways. Of the 101 accessory pathways, 56 were overt and 45 concealed. Only 19 patients have had a previous electrophysiology study, in the others, the study and the ablation were performed simultaneously. The location of the accessory pathways were as follows: 61 pathways in the free wall of the left ventricle, 4 in the free wall of the right ventricle, 25 in the left posteroseptal region, 9 in the right posteroseptal region and 2 in the right anteroseptal area. The time required for the diagnostic component of the electrophysiology study, the ablation procedure and the fluoroscopic time was recorded for each patient. Ninety-one of 101 accessory AV connections were successfully ablated (90%). Our success rate for the initial attempt was 87%. We had the opportunity to do a second attempt in only 4 out of 14 patients. The mean time of the procedure, including the electrophysiology test and the ablation was 95.6 %/-55.3 minutes. We have had a recurrence of 9% and 4% of non fatal complications. Radiofrequency catheter ablation can be performed safely and with a high success rate. PMID- 8466366 TI - [Coronary angioplasty in patients not accepted for surgical treatment. The initial experience of the Ignacio Chavez Instituto Nacional de Cardiologia]. AB - Coronary angioplasty has shown its efficacy in "high-risk" patients for surgical treatment (severe left ventricular failure, serious pulmonary or systemic disease). We studied a subgroup with multivessel coronary heart disease treated with coronary angioplasty because they were no candidates for surgery due to unsuitable coronary anatomy. Revascularization rate was determined in each patient as revascularization percentage obtained, compared with all the technically suitable lesions for coronary angioplasty. Ten patients (mean age 63 years) were studied, eight of them had unstable angina. Overall, 44 lesions were considered technically suitable for angioplasty and thirty-five could be dilated, technical success rate was 88% (31/35 lesions) and revascularization rate was 71% (31/44 lesions). Primary success rate was achieved in nine patients. Clinical follow-up varied from two to thirteen months (mean 7.8 months); eight patients have remained asymptomatic (class I of NYHA), another patient had stable angina and the other one had sudden death six months after the procedure. In conclusion, we demonstrated a high success rate in a short and long term with coronary angioplasty in a subgroup of patients with multivascular coronary heart disease that had been rejected for surgery due to unsuitable coronary anatomy. PMID- 8466367 TI - [The treatment of infectious endocarditis. Cefotaxime versus "traditional" medical management]. AB - We performed an open study to compare efficacy and renal toxicity of cephotaxime versus the usual beta lactam plus aminoglucoside treatment of infectious endocarditis. Twenty cases were studied, 10 treated with cephotaxime 4 g/day per 21 days and aminoglucoside for only 10 days. Comparison group received a combination of different beta lactam antibiotic plus aminoglucoside for 21 to 50 days, these patients were under care of nonparticipant physicians. Although cephotaxime treatment was as good as conventional antimicrobial scheme for control of infectious endocarditis, the treatment cost increases, and there is only marginal benefit in regard renal toxicity. PMID- 8466368 TI - [Percutaneous transvenous mitral commissurotomy with a Medi-tech balloon catheter: the initial experience and midterm follow-up]. AB - From Jan-21-91 to Jan-8-92 we performed percutaneous transvenous mitral commissurotomy (PTCM) with a Medi-tech balloon catheter (MBC) in 41 patients bearing mitral stenosis simple o predominant. We utilized an anterograde transseptal approach in order to access the mitral valve, the procedure failed in 5 patients, in 30 of them we used double MBC and single MBC were utilized in 6 patients. Both left ventriculogram and hemodynamic parameters were taken before and after PTCM. Posterior to PTCM an important decrease appeared in the mitral transvalvular gradient from 20.6 +/- 2.7 to 2.4 +/- 1.7 mmHg (p < 0.0001) and an average pressure of pulmonary artery of 46.2 +/- 9.8 to 23.9 +/- 6 mmHg (p < 0.0001), and also the pulmonary arterial resistance from 1178.1 to 557.1 dinas/cm 5/seg. There was an important concomitant increase in mitral valvular area from 0.84 +/- 0.11 to 2.38 +/- 0.08 cm2 (p < 0.0001) and in cardiac rate from 2.7 +/- 0.7 to 2.9 +/- 0.52 L/min (p < 0.001). COMPLICATIONS: Two female patients developed cardiac tamponade, one of them the procedure was successful, and for the other it was decided to submit her to valvular replacement. Mitral insufficiency was present in three patients; GI/IV in two of them and GII/IV angiographic in one. Another patient presented cerebral thromboembolism with complete recovery within 15 days. Short left to right shunt was detected only in 8 patients being 1.2/1 in 6 of them, 1.3/1 in one and 1.4/1 in other patient. Thirty three uncomplicated were dismissed within a maximum of 48 hours after procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466369 TI - [An overview of nuclear magnetic resonance in the study of the heart and major vessels]. PMID- 8466370 TI - [The cardiovascular effects of cocaine (I)]. PMID- 8466371 TI - [Radiofrequency ablation, a new technic in the treatment of tachyarrhythmias]. PMID- 8466373 TI - Morning vs afternoon exertion. Both are safe, but which is safer? PMID- 8466372 TI - [Interventional cardiology in Aguascalientes. The first 2 years of experience]. PMID- 8466374 TI - Approaches to asthma management. Realities and recommendations. AB - As asthma prevalence continues to increase, so does its impact on public health and on health care systems. Despite the prescription of more antiasthma medications than ever before, morbidity and mortality associated with asthma continue to increase. The focus of asthma therapy is changing, with a greater emphasis on control of the inflammatory rather than the bronchoconstrictive component. Several sets of guidelines recently developed by groups of asthma specialists clearly reflect this new focus. While such recommendations are intended to help physicians more accurately diagnose asthma by severity and better manage its symptoms, uniformity in both areas is lacking. Disparities are seen not only among physicians overall but also among primary care physicians compared with subspecialists. New survey data help to illustrate how reality--the clinical approaches of these physician subgroups--differs from current recommendations. Physicians who treat patients with asthma may find that their approaches are in agreement with those of their peers. Nonetheless, they may also find that they deviate from guidelines that could improve clinical outcome for a substantial number of patients with asthma. PMID- 8466375 TI - Should patients with heart disease exercise in the morning or afternoon? AB - OBJECTIVE: To compare the cardiovascular risk of exercise in the morning and afternoon in patients with established heart disease. DESIGN: Retrospective cohort study. PATIENTS: Patients with established heart disease referred for participation in a comprehensive cardiac rehabilitation program. INTERVENTION: Supervised, submaximal exercise (1 hour three times per week) performed either in the morning (7:30 AM) or the afternoon (3 PM). MAIN OUTCOME: Documented cardiac events that occurred while patients were exercising in the rehabilitation programs. RESULTS: There were five cardiac events in 168,111 patient-hours of exercise in the morning, with an incidence of 3.0 +/- 1.3 events per 100,000 patient-hours. There were two events during the 84,491 patient-hours of exercise in the afternoon, for an incidence of 2.4 +/- 1.5 events per 100,000 patient hours (not significant). The risk ratio of cardiac events during exercise in the morning compared with the afternoon was 1.27 (95% confidence interval, 0.25 to 6.55). CONCLUSION: In patients with coronary artery disease, the incidence of cardiac events is low during regular, submaximal exercise whether performed in the morning or the afternoon. PMID- 8466376 TI - The use of an indwelling Teflon catheter for subcutaneous heparin administration during pregnancy. A randomized crossover study. AB - BACKGROUND: The use of subcutaneous heparin, the therapy of choice for women requiring anticoagulant prophylaxis during pregnancy, is problematic because of the discomfort produced by repeated injections. An indwelling subcutaneous Teflon catheter that can be left in place for 1 week recently became available for use as an entry port for parenteral therapy. Since the use of this catheter has the potential to overcome some of the problems of long-term heparin therapy, we decided to compare this Teflon catheter with twice-daily subcutaneous injections in women requiring heparin during pregnancy. METHODS: In a randomized, multiple crossover study, patients alternated every 2 weeks between having heparin administered through the indwelling Teflon catheter and receiving heparin via subcutaneous injections. After each 4-week cycle, patients completed a questionnaire designed to determine their preferred method of heparin administration. The side effects, doses, and anticoagulant activity of heparin with the two delivery systems were also compared. RESULTS: Twelve patients completed one to five 4-week cycles of heparin therapy. Ten of the patients selected the Teflon catheter as the preferred route of heparin administration (P = .04) and 11 patients reported that the catheter caused less pain and bruising than twice-daily subcutaneous injections (P < .01). Five patients developed urticarial reactions at the sites of heparin injections. These reactions tended to be more severe when the Teflon catheter was used, and two women discontinued using the catheter after the first cycle because of this complication. There were no differences in heparin dose requirements or achieved activated partial thromboplastin times between the two routes of heparin administration. CONCLUSIONS: Most pregnant women in our study preferred to have subcutaneous heparin administered through an indwelling Teflon catheter rather than by twice daily injections. Heparin given through the Teflon catheter was bioavailable and caused less local bruising than twice-daily injections. Urticarial reactions to heparin tended to be more severe with the use of the Teflon catheter and resulted in the discontinuation of the device's use in two of 12 patients. PMID- 8466377 TI - Weight loss intervention in phase 1 of the Trials of Hypertension Prevention. The TOHP Collaborative Research Group. AB - BACKGROUND: Phase 1 of the Trials of Hypertension Prevention was a collaborative, randomized controlled clinical trial designed to determine the feasibility and efficacy of selected nonpharmacologic interventions in reducing or preventing an increase in diastolic blood pressure. METHODS: Participants aged 30 to 54 years who had a high-normal diastolic blood pressure (80 to 89 mm Hg), and were between 115% and 165% of their desirable body weight, were randomly assigned to either an 18-month weight loss intervention (n = 308) or a usual-care control condition (N = 256). Intervention consisted of 14 weekly group meetings followed by monthly maintenance sessions. Intervention participants received training in behavioral self-management technique and were asked to make life-style changes aimed at achieving a moderate reduction in energy intake and an increase in physical activity. RESULTS: The average weight losses in the intervention group at 6, 12, and 18 months of follow-up were 6.5, 5.6, and 4.7 kg for men and 3.7, 2.7, and 1.6 kg for women. The mean (+/- SE) change in diastolic blood pressure for intervention participants compared with controls at termination was -2.8 +/- 0.6 mm Hg for men and -1.1 +/- 0.9 mm Hg for women. For systolic blood pressure, the corresponding change was -3.1 +/- 0.7 mm Hg for men and -2.0 +/- 1.3 mm Hg for women. Blood pressure reductions were greater for those who lost larger amounts of weight. Sex-related differences in blood pressure response were largely due to the smaller amount of weight lost by women, and sex differences in weight loss could be accounted for by differences in baseline body weight. CONCLUSIONS: During an 18-month follow-up period, this weight reduction program was shown to be an effective nonpharmacologic intervention for reducing blood pressure in overweight adults with high-normal blood pressure. PMID- 8466378 TI - The superiority of antimicrosomal over antithyroglobulin antibodies for detecting Hashimoto's thyroiditis. AB - BACKGROUND: Antimicrosomal (anti-M) and antithyroglobulin (anti-Tg) antibodies are commonly measured together to detect Hashimoto's thyroiditis. Since this nearly doubles the cost of testing for one antibody, we wished to determine whether significant diagnostic loss would occur if the two tests were replaced by anti-M alone. METHODS: Both tests were performed in 2030 consecutive patients referred by general internists and endocrinologists. RESULTS: With a positive result defined as either test being positive at a 1:100 dilution, anti-M was much more sensitive than anti-Tg. Anti-M was positive in 99% (823/831) of all patients with positive tests, while anti-Tg was positive in 36% (302/831). Anti-M was the only positive test in 64% of all patients with positive tests, while anti-Tg was the only positive test in 1%. With a cutoff point of 1:400 dilution, the results were similar. CONCLUSIONS: Anti-M alone appears sufficient to detect autoimmune thyroid disease at about one half the cost of routinely performing both anti-M and anti-Tg studies. The widespread practice of performing both tests increases the cost without an offsetting diagnostic gain. PMID- 8466379 TI - Clinically significant hearing loss in renal allograft recipients treated with intravenous erythromycin. AB - BACKGROUND: Hearing loss is generally regarded as a rare side effect of erythromycin therapy. However, our own clinical experiences in erythromycin treated patients led us to suspect that this complication may be more common among renal allograft recipients. The purpose of this study was to evaluate the incidence, predisposing factors, clinical characteristics, and outcomes of erythromycin-induced hearing loss among renal allograft recipients. METHODS: We reviewed medical records of renal transplant patients treated for pneumonia with intravenous erythromycin lactobionate. Patients were evaluated for the occurrence of clinically significant hearing loss (including onset, duration, and reversibility), other signs and symptoms of ototoxicity (vertigo and tinnitus), daily erythromycin dose and duration of treatment, concurrent ototoxic drug therapy, renal and hepatic function, and history of previous otic disease. RESULTS: Eleven (32%) of 34 courses of intravenous erythromycin therapy resulted in hearing loss. The incidence of hearing loss was 53% (eight of 15 courses) in patients treated with 4 g of erythromycin daily compared with 16% (three of 19 courses) among those receiving 2 g/d (P = .05). In addition, courses of erythromycin were longer in those suffering auditory toxicity (9.6 +/- 4.7 days) than in nontoxic patients (5.7 +/- 3.6 days) (P < .05). Hepatic and renal function did not differ between toxic and nontoxic patients. All episodes of erythromycin-induced hearing loss were reversible. CONCLUSIONS: We conclude that clinically significant hearing loss occurs in more than 30% of renal allograft recipients treated for pneumonia with intravenous erythromycin lactobionate. Patients who require prolonged courses of erythromycin and those treated with 4 g/d are at particular risk for the development of auditory toxicity. With prompt recognition and modification of therapy, erythromycin-induced hearing loss appears to be completely reversible. PMID- 8466380 TI - Thyrotoxicosis followed by hypothyroidism in patients treated with amiodarone. A possible consequence of a destructive process in the thyroid. AB - Amiodarone is an iodine-rich drug used in the treatment of resistant cardiac arrhythmias. Amiodarone-induced thyrotoxicosis (AIT) is well recognized and is generally believed to be due to the excess iodine released from the metabolism of the drug, although amiodarone-associated thyroiditis has occasionally been observed. We report the clinical, laboratory, and therapeutic course of nine patients with AIT. The thyrotoxic phase was often followed by mild hypothyroidism during and after antithyroid drug or corticosteroid therapy. The thyroid was tender to palpation in two patients and a fine-needle aspiration biopsy of the thyroid revealed changes consistent with thyroiditis in three patients who underwent biopsy. These findings strongly suggest that the etiology of AIT, at least in some patients, is due, in part, to drug-induced inflammatory changes in the thyroid, as has been reported to occur in lung, bone marrow, and testes. Thus, the AIT may be due to excess iodine, drug-induced thyroiditis, or a combination of the two. The favorable response of AIT to corticosteroids in occasional patients previously reported also suggests that acute thyroiditis was probably present. PMID- 8466381 TI - Vasospastic angina associated with menses. PMID- 8466382 TI - Esophagogastroduodenoscopy for suspected gastrointestinal deposits. PMID- 8466383 TI - Anti-atherogenic effect of nuts: is the answer NO? PMID- 8466384 TI - Coffee and coronary heart disease. PMID- 8466385 TI - Reliability of DSM-III-R anxiety disorder categories. Using the Anxiety Disorders Interview Schedule-Revised (ADIS-R). AB - A large reliability study of DSM-III-R anxiety disorders is reported in which outpatients (n = 267) received two independent structured interviews (Anxiety Disorders Interview Schedule-Revised). It is the only reliability study to date in which the final DSM-III-R criteria are used throughout the study. Reliability was assessed for each diagnosis when it was assigned as a principal diagnosis and when it was assigned as either a principal or an additional diagnosis. Excellent reliability was obtained for current principal diagnoses of simple phobia, social phobia, and obsessive-compulsive disorder. Agreement was good for panic disorder when all severity levels of agoraphobic avoidance were combined. Reliability was fair for generalized anxiety disorder. Remaining diagnostic difficulties, particularly in identifying levels of agoraphobic avoidance and in reliably diagnosing generalized anxiety disorder, are discussed in the context of changes in diagnostic criteria that are under consideration for DSM-IV. PMID- 8466386 TI - A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. AB - We studied 4042 Vietnam era veteran monozygotic and dizygotic male twin pairs to determine the effects of heredity, shared environment, and unique environment on the liability for 15 self-reported posttraumatic stress disorder symptoms included in the symptom categories of reexperiencing the trauma, avoidance of stimuli related to the trauma, and increased arousal. Quantitative genetic analysis reveals that inheritance has a substantial influence on liability for all symptoms. Symptoms in the reexperiencing cluster and one symptom in the avoidance and numbing cluster are strongly associated with combat exposure, and monozygotic pairs are more highly concordant for combat exposure than dizygotic pairs. By fitting a bivariate genetic model, we show that there are significant genetic influences on symptom liability, even after adjusting for differences in combat exposure; genetic factors account for 13% to 30% of the variance in liability for symptoms in the reexperiencing cluster, 30% to 34% for symptoms in the avoidance cluster, and 28% to 32% for symptoms in the arousal cluster. There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms. PMID- 8466387 TI - Abnormal noradrenergic function in posttraumatic stress disorder. AB - To evaluate possible abnormal noradrenergic neuronal regulation in patients with posttraumatic stress disorder (PTSD), the behavioral, biochemical, and cardiovascular effects of intravenous yohimbine hydrochloride (0.4 mg/kg) were determined in 18 healthy male subjects and 20 male patients with PTSD. A subgroup of patients with PTSD were observed to experience yohimbine-induced panic attacks (70% [14/20]) and flashbacks (40% [8/20]), and they had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol levels, sitting systolic blood pressure, and heart rate than those in healthy subjects. In addition, in the patients with PTSD, yohimbine induced significant increases in core PTSD symptoms, such as intrusive traumatic thoughts, emotional numbing, and grief. These data were consistent with a large body of preclinical data that indicated that uncontrollable stress produces substantial increases in noradrenergic neuronal function. We discuss the implications of these abnormalities in noradrenergic functional regulation in relation to the long-term neurobiological sequelae of severe uncontrollable stress and the pathophysiological relationship between PTSD and other anxiety disorders, such as panic disorder. PMID- 8466388 TI - Effect of innervation on heart rate response to mental stress. AB - Heart transplant recipients provide a useful model for study of the autonomic control of the cardiovascular response to mental stress. Utilizing the innervated native atrial tissue of heart transplant recipients as an internal control exposed to the same circulatory milieu as the denervated graft heart was exposed to, the effect of innervation on the heart rate response to a mentally stressful arithmetic task was examined in eight subjects. Compared with the graft, the innervated atrial tissue manifested a larger heart rate increase during the task, larger heart rate decrease after the task, and more rapid rate of change in heart rate during the task and recovery periods. Thus, cardiac denervation results in a chronotropic response to mental arithmetic-induced stress that is blunted and more gradual than that of the innervated heart but not completely eliminated. The cardiac chronotropic response to mental arithmetic stress is dependent on both humoral factors and, predominantly, its direct autonomic innervation. PMID- 8466389 TI - Panic attacks during placebo procedures in the laboratory. Physiology and symptomatology. AB - Heart rate, respiratory measurements, and Acute Panic Inventory symptoms of 17 patients with panic disorder who experienced panic attacks during a placebo infusion (situationally provoked panic) were analyzed and compared with similar data from a group of 19 patients with panic disorder who panicked during lactate infusion. Previously, it was shown that the group with lactate-induced panic attacks exhibited increased minute ventilation compared with normal control subjects and nonpanicking patients with panic disorder during lactate infusion. The group with situationally provoked panic attacks exhibited significant increases in both heart rate and minute ventilation immediately preceding the onset of the panic attack. The increase in minute ventilation appeared to be caused more by increase in tidal volume than in respiratory frequency. The increase in heart rate in the group with situationally provoked panic attacks was very similar to that seen in the group with lactate-induced panic attacks, but the group with situationally provoked panic attacks appeared to have somewhat greater increase in minute ventilation than the group with lactate-induced panic attacks. This suggests that the metabolic alkalosis produced by lactate infusion might actually blunt the full expression of panic-associated respiratory stimulation. These data validate the belief that significant cardiorespiratory stimulation occurring during panic attacks in the laboratory is not simply secondary to the intrinsic physiologic effects of panic-inducing substances such as lactate, yohimbine, and carbon dioxide. PMID- 8466390 TI - A direct interview family study of social phobia. AB - Risks for DSM-III-R anxiety and affective disorders and "subdisorder" (nonimpairing) irrational social fears, among directly interviewed first-degree relatives (n = 83) of probands who met criteria for social phobia but for no other lifetime anxiety disorder diagnosis, were contrasted to risks for disorder among similarly evaluated relatives (n = 231) of never mentally ill controls. Relatives of social phobia probands had a significantly increased risk for social phobia (16% vs 5%, relative risk = 3.12) but not for other anxiety disorders. These results suggest a familial contribution to the development of some cases of social phobia. The specificity of the pattern of intergenerational transmission is consistent with the current nosologic distinction between social phobia and other anxiety disorders. PMID- 8466391 TI - Psychobiologic mechanisms of posttraumatic stress disorder. PMID- 8466393 TI - The professional historical error. PMID- 8466392 TI - False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. AB - A carbon dioxide hypersensitivity theory of panic has been posited. We hypothesize more broadly that a physiologic misinterpretation by a suffocation monitor misfires an evolved suffocation alarm system. This produces sudden respiratory distress followed swiftly by a brief hyperventilation, panic, and the urge to flee. Carbon dioxide hypersensitivity is seen as due to the deranged suffocation alarm monitor. If other indicators of potential suffocation provoke panic this theoretical extension is supported. We broadly pursue this theory by examining Ondine's curse as the physiologic and pharmacologic converse of panic disorder, splitting panic in terms of symptomatology and challenge studies, reevaluating the role of hyperventilation, and reinterpreting the contagiousness of sighing and yawning, as well as mass hysteria. Further, the phenomena of panic during relaxation and sleep, late luteal phase dysphoric disorder, pregnancy, childbirth, pulmonary disease, separation anxiety, and treatment are used to test and illuminate the suffocation false alarm theory. PMID- 8466394 TI - The psychological impact of the Gulf War: a study of acute stress in Israeli evacuees. PMID- 8466395 TI - College of American Pathologists Conference XXIII on matrix effects and accuracy assessment in clinical chemistry: introduction. PMID- 8466396 TI - Matrix effects on proficiency testing materials. Impact on accuracy of cholesterol measurement in laboratories in the nation's largest hospital system. AB - The objective of this collaborative study with the Department of Veterans Affairs (VA), College of American Pathologists (CAP), and the Centers for Disease Control and Prevention (CDC) was to quantitate the matrix-induced biases of cholesterol measurements on the CAP Comprehensive Chemistry Surveys materials used in proficiency testing (PT). A total of 174 VA Medical Centers outpatient clinics and clinical laboratories participate in the VA-CDC National Cholesterol Standardization and Certification Program. This study was conducted in 112 VA laboratories that have been standardized for measuring cholesterol accurately (within +/- 3.0% of the CDC reference-method values) using fresh, unfrozen, unadulterated human serum samples. Fresh serum samples and 1990 CAP Surveys materials were sent by overnight mail, and the laboratories were asked to analyze them simultaneously in triplicate in a single analytic batch run. The results showed significant matrix-effect biases with the CAP Surveys materials with six of the eight major peer groups, despite the fact that accuracy of cholesterol measurements was maintained with fresh serum samples. The magnitude and direction (positive or negative) of the matrix-effect biases were instrument, reagent, and method specific using the following peer groups: du Pont Dimension (-8.9%); Beckman CX4, CX5, and CX7 (-5.5%); Kodak Ektachem 400, 500, and 700 (+4.4%); Instrumentation Laboratory Monarch (-3.1%); Baxter Paramax (-2.4%); Technicon SMAC and RA (+1.3%); Hitachi/BMD 704 through 747 (+0.4%); and Abbott Spectrum ( 0.3%). The CAP PT materials used currently do not behave in a manner identical to fresh human serum when measuring cholesterol on many, but not all, analytic systems. The observed biases due to "matrix effects" with PT materials will cause incorrect conclusions about the accuracy of many laboratory procedures performed on fresh patient specimens. This matrix-effect phenomenon will severely hamper interlaboratory accuracy transfer, standardization efforts, and monitoring performance of a laboratory's testing accuracy with the use of the current survey materials used in PT programs. Collaborative efforts are needed to (1) improve PT fluids to analytically behave more like fresh, human serum; (2) improve instrument design and reagent formulation; and (3) select methods and methodologic parameters that are more "robust" and less sensitive to the exact character of processed calibrators, quality control, and PT materials. PMID- 8466397 TI - Accurate enzyme activity measurements. Two decades of development in the commutability of enzyme quality control materials. AB - Commercial serum preparations are integral components of both internal and external quality control programs for enzyme activity measurements. However, properties of these materials may differ significantly from those of clinical specimens. Differences from clinical specimens may include the following: species origin of the enzyme; isoenzyme form(s); integrity of the molecular species; matrix of the solution; processes such as lyophilization; and addition of preservatives. There are also significant differences among methods measuring the activity of a single enzyme including a diversity of compounds that may serve as substrate(s); variable cofactor or metal supplementation; and differences in the substrate concentration(s), buffer substances, pH, and temperature. The measured response to each of these variations in assay technique may differ among these types of specimens. To be acceptable, quality control materials must have properties similar to those of clinical specimens. Thus, the concept of commutability that we originated and first applied to enzyme activity measurements remains useful, and its further application to the problem of "matrix effects" is reviewed here. Multivariate display techniques are applied to the specific examples of aspartate aminotransferase, alpha-amylase, and alkaline phosphatase to judge the commutability of quality control materials for these enzymes. PMID- 8466398 TI - Matrix effects in blood gas proficiency testing. AB - Materials currently used for blood gas proficiency testing are unlike whole blood in several obvious respects, which by definition introduces matrix effects as possible sources of error that can affect proficiency testing results. Data from recent College of American Pathologists surveys are reviewed and aqueous and fluorocarbon matrices for PO2 and PCO2 testing are compared. Closely related to matrix effects are other sources of error unique to proficiency testing samples, such as sample temperature and sample packaging. Proficiency testing programs are seriously hampered by not being able to use either whole blood or a better surrogate than is currently available. In particular, the use of aqueous materials has the potential to penalize participant laboratories unfairly in some cases and to turn proficiency testing into a meaningless exercise in others. PMID- 8466399 TI - Review of the influence of polypeptide hormone forms on immunoassay results. AB - Various forms of the polypeptide hormones that occur in blood, fluids, or tissues can differ according to physiologic and pathologic states. Forms include subunits of luteinizing hormone, follicle-stimulating hormone, human chorionic gonadotropin, and thyroid-stimulating hormone. Hormonal isoforms occur for these hormones as well as for prolactin and growth hormone. Variation in hormonal forms appears to contribute significantly to the wide variation in immunoassay results for these polypeptide hormones. Subunits and isoforms of the polypeptide hormones can overreact or underreact in monoclonal antibody assays. The underreaction or overreaction can occur with standards, controls, and patient specimens as well as with the assay label. PMID- 8466400 TI - Matrix effects in therapeutic drug monitoring surveys. Proposed protocol to identify error components and quality improvement opportunities. AB - Therapeutic drugs are not endogenous compounds. Therefore, differing reactivities between proficiency testing and patient samples have potential mechanisms beyond those attributable to alterations of the serum protein base, stabilizing materials, and other manufacturing components. The therapeutic drug monitoring proficiency sample is the ultimate in polypharmacy. Cross-reactivities may be uncovered that may or may not occur with any frequency in patient samples. Drugs are present in therapeutic drug monitoring proficiency samples in the absence of their metabolites, which may alter interactions with the assay systems. The CAP Therapeutic Drug Monitoring Resource Committee has contacted manufacturers when a specific method yields proficiency test results that differ from all other methods and/or the weighed-in target values. Only a few examples have been formally evaluated with the "matrix evaluation protocol." The protocol is very useful and has identified some matrix effects. A protocol is proposed using multiple samples containing survey base material. Data analysis using reciprocal plots will identify interference and corroborate calibration or recovery errors in the presence of survey base material. Data from 1987 through 1991 surveys for lithium and theophylline illustrate this data analysis and show interference from other drugs and suggest calibration errors. Weighted-in target values are the most rigorous method to provide accurate, transferable patient results and convince ourselves and our evaluators that we know what we are measuring. All of us need to be committed to improvement of laboratory procedures. I believe weighed-in target values are the appropriate and achievable goal for proficiency testing the majority of therapeutic drug monitoring analytes. Implementation of target values requires diligent and intricate collaboration among laboratorians, surveyors, manufacturers, and regulators. PMID- 8466401 TI - Accuracy verification and identification of matrix effects. The College of American Pathologists' Protocol. AB - Proficiency testing using stabilized control materials has been used for decades as a means of monitoring and improving performance in the clinical laboratory. Often, the commonly used proficiency testing materials exhibit "matrix effects" that cause them to behave differently from fresh human specimens in certain clinical analytic systems. Because proficiency testing is the primary method in which regulatory agencies have chosen to evaluate clinical laboratory performance, the College of American Pathologists (CAP) has proposed guidelines for investigating the influence of matrix effects on their Survey results. The purpose of this investigation was to determine the feasibility, usefulness, and potential problems associated with this CAP Matrix Effect Analytical Protocol, in which fresh patient specimens and CAP proficiency specimens are analyzed simultaneously by a field method and a definitive, reference, or other comparative method. The optimal outcome would be that both the fresh human and CAP Survey specimens agree closely with the comparative method result. However, this was not always the case. Using several different analytic configurations, we were able to demonstrate matrix and calibration biases for several of the analytes investigated. PMID- 8466402 TI - Statistical power in the detection of matrix effects. AB - Matrix-induced bias can adversely affect the performance evaluation a clinical laboratory receives on proficiency testing results. Therefore, it is vital that matrix effects from a matrix-biased system are detected and that laboratories using these systems are not falsely penalized on their proficiency testing results. The College of American Pathologists has developed an experimental protocol to test whether an observed bias is, in fact, due to the proficiency testing sample matrix rather than true performance or calibration problems. The probability of detecting a matrix effect using this protocol given a matrix biased system is defined as statistical power. Five parameters are known to affect the probability of detection: (1) size of the bias in the proficiency testing material, (2) lack of fit coefficient of variation-natural variation in patient samples used to define the relationship between the test and reference methods, (3) pure error coefficient of variation-random variation in the test method, (4) the number of fresh patient samples, and (5) the number of replicates for each sample. The level of significance of the statistical test will also affect the probability of detection. Power curves are generated to show the effect these five parameters have on the determination of power. With the exception of bias, power is most influenced by the components of variance, lack of fit (nonlinear), and pure (random) error. Of these two components, the lack of fit error, which represents an uncontrollable source of error, is usually more influential than pure error, which can be reduced by a larger number of replicates. A large increase in power will result from an increase of fresh patient samples from 10 to 20, and a moderate increase in power will result from an increase of fresh patient samples from 20 to 40; no noticeable increase in power is seen with greater than 40 fresh patient samples. Large increases in power were observed for increases in the number of replicates per sample from one to two, two to three, and three to five. To markedly increase power further, 10 replicates would have to be assayed. PMID- 8466403 TI - Matrix effects and the accuracy of cholesterol analysis. AB - We found evidence of bias due to matrix effect in 70% of 37 instrument/reagent specific systems analyzing the total cholesterol content of a lyophilized proficiency testing material. We used a computational method to remove bias due to matrix effect from the proficiency testing database. After correction for matrix effect bias and when compared with the reference method, 92% to 93% of results for three lyophilized proficiency testing samples analyzed in 1989 and 1990 met the 1992 National Cholesterol Education Program total error goal of 8.9%, and 94% to 95% met the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) goal of 10%. However, compared with the definitive method for total cholesterol, the calibration bias of 41% of 37 peer groups exceeded the 1992 National Cholesterol Education Program goal for bias of 3%. Because the calibration bias of the method is incorporated into the peer group mean, use of peer group means as target values to assess result acceptability hinders advancement of the state of the art in interlaboratory comparability and the clinical effectiveness of laboratory testing. The prevalence of matrix effects has prevented successful application of accuracy-based evaluation of cholesterol test proficiency. The establishment of predictable recovery, preferably complete recovery, of cholesterol from reference materials is an important priority for cholesterol test methods. However, adjustment of proficiency testing results to remove the average bias due to matrix effects can help assess the actual state of the art in cholesterol test accuracy. PMID- 8466404 TI - Matrix effects and accuracy assessment. Identifying matrix-sensitive methods from real-time proficiency testing data. AB - Retrospective proficiency testing data may be used to screen for matrix effect, which is suspected when significant methodologic bias is detected. Prioritization is centered on those situations where relatively high unacceptability rates are associated with high bias. Before attributing high unacceptability rates to methodologic bias, factors such as peer grouping strategies, number of participants in peer groups, analyte concentration, evaluation limits, and interparticipant precision, all of which affect scoring, need to be considered. When bias-associated high unacceptability rates are detected, methods are candidates for further evaluations to identify the causes of bias, to determine if matrix effect is present. Using outputs from the College of American Pathologists Survey Management Enhancement Program, we have presented data from the 1991 Comprehensive Chemistry Survey to demonstrate methodology to study this problem, and have selected examples of method performance in which tabular and graphic information contribute to its study. For the analytes studied, unacceptability rates tend to be greatest in association with high methodologic bias and/or between-participant imprecision relative to external evaluation limits, samples at the upper extreme of analyte concentration, low numbers of participants in peer groups, grading by comparative method, and concentration independent fixed evaluation limits. Specific examples of significant bias that is possibly matrix induced are presented for uric acid, glucose, creatinine, and total protein. PMID- 8466405 TI - Achieving accuracy for routine clinical chemistry methods by using patient specimen correlations to assign calibrator values. A means of managing matrix effects. AB - Accurate results obtained from routine methods used in the clinical laboratory can be achieved if the methods are traceable to definitive or reference methods or are based on widely accepted methodologic principles. At Eastman Kodak Co (Rochester, NY), we assign calibrator values for each method that is available on Kodak Ektachem analyzers by correlation to a reference method or a methodologic principle using patient specimens. Kodak's Reference Laboratory is responsible for maintaining the accuracy and consistency of the reference method or methodologic principle by standardizing with National Institute of Standards and Technology materials, where available, monitoring performance through statistical process control, participating in proficiency testing programs, and following procedures consistent with the International Organization for Standardization guideline, "General Requirements for the Competence of Calibrations and Testing Laboratories (ISO 25). "Patient samples that span the reportable range are run in replicate on the reference method or methodologic principle over several days. These patient sample results are then used to create a calibration curve based on the relationship of concentration to the raw response of the routine method, where the same patient samples are also run in replicate on the same day. Each day, multiple vials of stable calibrator fluids are included in these tests, along with control materials. Each calibrator is assigned a value of equivalent concentration (in millimoles per liter) by predicting the concentration that would be present at the measured response if the test fluid were a patient sample. These are termed supplementary assigned values (SAVs). The same calibrators can be used to compensate for matrix effects resulting from changes in reagent formulations, by appropriately adjusting the assigned values. For example, when a process improvement for Kodak Ektachem clinical chemistry slides for phosphorus was introduced, an SAV change of 0.39 mmol/L (1.2 mg/dL) was required for one calibrator to maintain accuracy of the patient samples. A comparison of patient samples, using the SAVs specific for each formulation, gave excellent correlation (in millimoles per liter; r2 = 0.995) by the following equation: New Formulation = 1.02 (Old Formulation) -0.016; Sy.x = 0.074. The benefits of this approach to calibration include (1) accuracy is traceable to a reference method or methodologic principle and, wherever available, to reference materials; (2) new calibrator values (SAVs) can be assigned whenever the reagent formulation changes to maintain accurate patient results; and (3) if matrix effects are present, they will not adversely influence accuracy because traceability is based on patient sample comparisons. PMID- 8466406 TI - Manufacturer's approach in transferring accuracy to multiple field installations. AB - Manufacturers of instrument systems for in vitro diagnostic use are closely regulated by the Food and Drug Administration and sell their products to clinical laboratories that participate in rigorous quality control and proficiency testing programs. In these circumstances, manufacturers must plan and implement procedures that will ensure acceptable accuracy and precision from all installed systems. This activity starts with the design goals and specifications and continues with manufacturing and quality assurance testing, through various postsale support services. This article outlines some specific instrumentation examples to demonstrate the accomplishment of these objectives. PMID- 8466407 TI - Problems in formulating method-insensitive proficiency testing materials. AB - Significant problems exist in formulating method-insensitive proficiency materials. Many steps are required in processing human plasma, and difficult choices are involved in the selection of appropriate materials to be added to the processed plasma. Additionally, analytes may vary widely in their recovery from method to method. To enhance understanding of the procedures and problems involved in the development and manufacture of proficiency materials, a number of constituents and their method-specific recoveries are reviewed. PMID- 8466408 TI - College of American Pathologists Conference XXIII on matrix effects and accuracy assessment in clinical chemistry. Report of Working Group on Proficiency Test Scoring. PMID- 8466409 TI - College of American Pathologists Conference XXIII on matrix effects and accuracy assessment in clinical chemistry: report of Working Group on Method Development. PMID- 8466410 TI - College of American Pathologists Conference XXIII on matrix effects and accuracy assessment in clinical chemistry. Report of Working Group on Materials Development. PMID- 8466411 TI - College of American Pathologists Conference XXIII on matrix effects and accuracy assessment in clinical chemistry. Report of Working Group on Proficiency Test Programs. PMID- 8466412 TI - College of American Pathologists Conference XXIII on matrix effects and accuracy assessment in clinical chemistry. Report of Working Group on Accuracy Transfer. PMID- 8466413 TI - The detection of problem analytes in a single proficiency test challenge in the absence of the Health Care Financing Administration rule violations. AB - The Clinical Laboratory Improvement Act of 1988 (CLIA 88) has dramatically changed proficiency testing (PT) practices having mandated (1) satisfactory PT for certain analytes as a condition of laboratory operation, (2) fixed PT limits for many of these "regulated" analytes, and (3) an increased number of PT specimens (n = 5) for each testing cycle. For many of these analytes, the fixed limits are much broader than the previously employed Standard Deviation Index (SDI) criteria. Paradoxically, there may be less incentive to identify and evaluate analytically significant outliers to improve the analytical process. Previously described "control rules" to evaluate these PT results are unworkable as they consider only two or three results. We used Monte Carlo simulations of Kodak Ektachem analyzers participating in PT to determine optimal control rules for the identification of PT results that are inconsistent with those from other laboratories using the same methods. The analysis of three representative analytes, potassium, creatine kinase, and iron was simulated with varying intrainstrument and interinstrument standard deviations (si and sg, respectively) obtained from the College of American Pathologists (Northfield, Ill) Quality Assurance Services data and Proficiency Test data, respectively. Analytical errors were simulated in each of the analytes and evaluated in terms of multiples of the interlaboratory SDI. Simple control rules for detecting systematic and random error were evaluated with power function graphs, graphs of probability of error detected vs magnitude of error. Based on the simulation results, we recommend screening all analytes for the occurrence of two or more observations exceeding the same +/- 1 SDI limit. For any analyte satisfying this condition, the mean of the observations should be calculated. For analytes with sg/si ratios between 1.0 and 1.5, a significant systematic error is signaled by the mean exceeding 1.0 SDI. Significant random error is signaled by one observation exceeding the +/- 3-SDI limit or the range of the observations exceeding 4 SDIs. For analytes with higher sg/si, significant systematic or random error is signaled by violation of the screening rule (having at least two observations exceeding the same +/- 1 SDI limit). Random error can also be signaled by one observation exceeding the +/- 1.5-SDI limit or the range of the observations exceeding 3 SDIs. We present a practical approach to the workup of apparent PT errors. PMID- 8466414 TI - Ethical considerations in rehabilitation medicine. AB - As the number of patients with chronic illness or disability grows, rehabilitation professionals will face increasingly difficult questions. Traditional concepts of medical ethics can help find solutions to some, but not all of those questions. Rehabilitation medicine needs an expanded vision of informed consent, one that embraces the needs of patients and promotes rehabilitation's educational model. To insure that rehabilitation professionals use this model appropriately, we need to make certain that their education integrates humanistic and caring virtues with medical knowledge and skill. PMID- 8466415 TI - Technique to improve chronic motor deficit after stroke. AB - The unaffected upper extremity of chronic stroke patients was restrained in a sling during waking hours for 14 days; on ten of those days, these patients were given six hours of practice in using the impaired upper extremity. An attention comparison group received several procedures designed to focus attention on use of the impaired upper extremity. The restraint subjects improved on each of the laboratory measures of motor function used--in most cases markedly. Extensive improvement, from a multi-year plateau of greatly impaired motor function, was also noted for the restraint group in the life situation and these gains were maintained during a two-year period of follow-up. For the comparison group only one measure showed small to moderate improvement, and this was lost during the follow-up period; there was essentially no overlap between the individuals of the two groups. Thus, prolonged restraint of an unaffected upper extremity and practice of functional movements with the impaired limb proved to be an effective means of restoring substantial motor function in stroke patients with chronic motor impairment identified by the inclusion criteria of this project. PMID- 8466416 TI - Patterns of visual spatial inattention and their functional significance in stroke patients. AB - The relationship between patterns of visual spatial inattention and activities of daily living (ADL) performance was investigated in 64 Chinese patients with right brain lesions, using the Klein-Bell ADL Scale and the Random Chinese Word Cancellation Test. The result showed that patients demonstrating hemi-inattention were significantly worse in ADL performance than patients with nonlateralized inattention or patients with normal attention, but that the latter two groups did not differ from each other. Although ADL performance was also found to be significantly related to somatosensation, motor status, and visual factors, after controlling the effects of these variables by partial correlation, hemi inattention still was highly related to ADL performance. Independence in dressing, mobility, and elimination appeared to be more adversely affected by hemi-inattention than were bathing/hygiene, eating, and telephone use. PMID- 8466417 TI - Traumatic brain injury as a risk factor for behavioral disorders in children. AB - The most common behavioral problems that are associated with traumatic brain injury in children are the same behaviors that prompt referral to special education for behavioral disorder. The purpose of this study was to determine whether there is an association between traumatic head injury in children and subsequent behavioral disorders for which special educational services are provided. A case-control design was used to compare occurrences of prior head injury in children receiving special educational services for behavioral disorders (cases) to similar occurrences in children in regular education (controls). Subjects included 170 case and 197 control students in grades 1 through 5 in a single large school district during 1988-1989. Data were collected by parent questionnaire and school record review. The odds ratio (OR) of a history of head injury among children with behavioral disorders relative to controls was 3.3 (95% confidence interval [CI] 1.3-8.3); the OR of a history of head injury sustained during the preschool years was 8.7 (95% CI 2.5-30.7) in cases relative to controls. Mean IQ scores were significantly lower for cases injured at two years of age or less in comparison with cases injured later. Full scale IQs (+/- SD) were 88 +/- 5 versus 107 +/- 14 (t = 3.5, p = .008), performance IQs 91 +/- 9 versus 108 +/- 12 (t = 3.0, p = .012), and verbal IQs 86 +/- 7 versus 106 +/- 15 (t = 3.2, p = .008). Achievement test results did not differ between cases with and those without histories of head injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466418 TI - Performance comparison among children fitted with myoelectric and body-powered hands. AB - Seventy-six children with unilateral below-elbow amputation were fitted in random sequence with a myoelectric (MYO) and a body-powered (BP) prosthetic hand of identical size, shape, and glove color. Subjects ranged from six to 17 years, nine months and included 67 children with congenital limb deficiency and nine who sustained traumatic amputation. After training, each child wore each hand for three months. On the form board test requiring only prosthetic use, subjects took 13.7% longer with the MYO and committed more errors with the MYO, specifically in dropping objects and delaying their grasp and release. Object displacement, the most common error, occurred nearly as often with BP as MYO. MYO was minimally faster on a test of ten practical activities designed for bimanual prehension. Card playing was 39.8% faster with BP, whereas donning socks, cutting paper, and bandage application were 27.8%, 12.5%, and 10.9% faster with MYO. Performance with both hands was rated as decidedly poorer than normal quality. No major clinically important differences were found in the comparison of performance. PMID- 8466419 TI - Gait parameters of children with spastic diplegia: a comparison of effects of posterior and anterior walkers. AB - The purpose of this study was to compare the effects of posterior and anterior walkers on the gait parameters of five children with spastic diplegic cerebral palsy. Computer-based kinematic analysis was used to investigate differences in gait. Gait laboratory data indicated that use of the posterior walker (1) facilitated more upright posture in these subjects, as seen in decreased trunk and hip flexion during stance phase; (2) decreased double stance time; and (3) increased walking velocity. According to parent report, both the parents and their children preferred the posterior walker. Most parents also reported that when using the posterior walker, their children walked more normally with increased stability and interacted more easily with other children. PMID- 8466420 TI - Rehabilitation approaches to children with osteogenesis imperfecta: a ten-year experience. AB - Twenty-five children with severe osteogenesis imperfecta were followed and treated with physical and occupational therapy for a mean of five years, two months, 80% since the first two years of life. According to their highest achieved motor skill, they fell into three groups: (A) able to stand in braces, (B) able to ambulate short distances without braces, and (C) able to ambulate in the community without assistance. Preventable functional impairment is caused in group A by shoulder joint and hand contractures and upper extremity weakness, group by hip flexion and plantar flexion contractures of the feet, shoulder joint contractures, and upper extremity weakness, and group C by poor lower extremity joint alignment, impaired balance, and low endurance. Appropriate rehabilitation strategies have led to slow, continued functional improvement in the majority of patients. Results of the ten-year retrospective study suggest that clinical groupings based in part on functional needs will enable the clinician to provide optimal rehabilitation services. PMID- 8466421 TI - Preprogrammed reactions in individuals with Down syndrome: the effects of instruction and predictability of the perturbation. AB - Preprogrammed reactions to unexpected loadings and unloadings of an elbow joint resisting an extending bias load were studied in subjects with Down syndrome. The subjects were instructed to either "let go" or "return back as fast as possible." Both predictable and unpredictable perturbation directions were used. Integrated electromyograms of the two elbow flexors and two elbow extensors were used to characterize the preprogrammed reactions. All the subjects were able to modulate their preprogrammed reactions in response to a change in the instruction. They were also able to grade the preprogrammed responses corresponding to the magnitude of the perturbation. Two basic patterns of modulation were observed, "reciprocal" and "coactivation." There were no effects of the predictability of the perturbation direction. Reconstructed joint compliant characteristics suggested an unchanged gain in the arc of the tonic stretch reflex. We propose that there are no abnormalities in the preprogrammed reactions of some individuals with Down syndrome. The apparent "clumsiness" of individuals with Down syndrome in a changing environment is assumed to reflect an adaptation to their impaired decision-making ability. The high variability of motor performance in subjects with Down syndrome may result from mixing different strategies for solving motor tasks. PMID- 8466422 TI - Exercise to improve gait velocity in older persons. AB - The effect of 12 weeks of resistance and balance training on strength and gait measures in older persons was tested in a randomized control trial. Thirty-one residents of two life-care communities volunteered (mean age, 82.1 years). The exercise group (E) trained three times per week, performing resistance training to fatigue for knee extension, hip abduction, ankle dorsiflexion, hip extension, and knee flexion, and postural control exercises. The control group (C) met weekly for flexibility exercises performed sitting in a chair. The exercise group achieved significant improvements in muscle strength and gait velocity (p < .05). Knee extension one maximum repetition increased 32% (24% to 40%, 95% confidence interval [CI]), from 55 +/- to 72 +/- 4N.m. Isokinetic knee extension torque increased 25% (3% to 47%) from 40 +/- 5 to 50 +/- 5N.m at 120 degrees s-1. Usual gait velocity increased 8% (3% to 13%) in E from 1.04 +/- .07 to 1.12 +/- .06m/s. There was a trend of improvement in maximal gait speed 4% (0 to 8%) from 1.43 +/- 0.1 to 1.49 +/- 0.1m/s, p = 0.054. Gait and strength measures in C were unchanged. A short-term exercise program that trained strength and balance achieved a clinically significant improvement in gait velocity. PMID- 8466423 TI - Quadriceps angle and rearfoot motion: relationships in walking. AB - The purpose of this study was to describe the relationship between quadriceps angle (q-angle) and rearfoot motion in walking. Twenty women were videotaped with two cameras, one located behind the subject and one located in front providing both front and rear views of the frontal plane. Each subject was required to walk at a 1.5 mph pace on a treadmill while five consecutive right footfalls were videotaped. After walking, each subject was videotaped in a calibrated stance and a chosen stance. Leg length and hip width were measured. Arch index was measured to determine arch type of the subject. All subjects were required to walk barefoot during testing. All trials were digitized and analyzed using the Peak Performance Motion Measurement System. Q-angles and rearfoot angles were calculated and averaged over the five trials. The following group means were obtained: maximum pronation (MPRO) was -7.88 degrees, total rearfoot motion (TRFM) was 8.20 degrees, static rearfoot angle in a chosen stance (SRFCHOS) was 3.45 degrees, static rearfoot angle in a calibrated stance (SRFCAL) was -2.40 degrees, dynamic q-angle at heel strike (DQHS) was 16.13 degrees, dynamic q-angle at midstance (DQMS) was 16.00 degrees, static q-angle in a chosen stance (SQCHOS) was 18.32 degrees, static q-angle in a calibrated stance (SQCAL) was 17.42 degrees, hip width (HWIDTH) was 25.66cm, leg length (LLENGTH) was 85.76cm and arch index was 0.23cm2. Pearson product moment correlations were calculated between each of the variables. All of the q-angle variables, both static and dynamic, correlated poorly with rearfoot motion variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466424 TI - Persistent facial myoclonus: a negative prognostic sign in patients with severe brain injury. AB - The determination of long-term prognosis is one of the most difficult tasks in the management of persons with brain injury (BI). Initial Glasgow Score, duration of coma, brain stem reflexes, and pupillary responses are all clinical findings that have been related to outcome in BI. We describe another easily observable clinical finding, persistent facial myoclonus (PFM), which may provide additional information on prognosis after severe BI. We retrospectively reviewed 295 consecutive admissions to an inpatient brain injury rehabilitation program. Data extracted included mechanism of injury, patient demographics, admission and discharge Rancho Level (RL), and presence of PFM plus first date of description. Of the total admissions, 68 (23%) were RL < or = 2 on admission and of those 68, nine (13%) demonstrated PFM. Twenty-seven of 59 patients without PFM advanced to RL > 3 but none of those with PFM progressed to RL > 2 (Fisher's exact probability = .007). Mean time from injury to PFM description was 10.5 months (SD = 11.8, range, 2.5 to 25.0 months) and mean time from description to discharge was 7.1 months (SD = 6.6, range, 2.0 to 22.5 months). Four of the nine PFM patients had evidence of brain stem injury on computed tomography or magnetic resonance imaging scans, a much higher percentage than in the larger population. We postulate that patients with PFM after TBI represent a subgroup of patients with severe diffuse axonal injury with brain stem lesions. PMID- 8466425 TI - Baltimore Therapeutic Equipment work simulator: energy expenditure of work activities in cardiac patients. AB - The energy expenditure and hemodynamic responses to tasks performed on the Baltimore Therapeutic Equipment (BTE) work simulator were evaluated in men with coronary artery disease and compared to tasks performed at a laboratory workstation in which actual tools and equipment were used. Met units for the BTE work simulator and corresponding workstation tasks, respectively, were drill press operation, 1.5 +/- 0.1 and 1.5 +/- 0.3Mets; hammering, 2.3 +/- 0.3 and 3.4 +/- 0.8Mets (p < 0.05); repetitive lifting a 22.7kg weight load, 3.8 +/- 0.6 and 4.5 +/- 0.9Mets (p < 0.05); mechanic work in a supine position, 2.0 +/- 0.5 and 1.7 +/- 0.2Mets; sanding wood, 2.0 +/- 0.3 and 2.5 +/- 0.7Mets; sawing wood, 3.2 +/- 0.6 and 4.3 +/- 0.7Mets (p < 0.05); screwdriving, 2.2 +/- 0.3 and 2.5 +/- 0.5Mets (p < 0.05); shoveling, 5.45kg load 4.6 +/- 1.0 and 4.2 +/- 0.7Mets; sweeping, 1.7 +/- 0.2 and 3.0 +/- 0.4Mets (p < 0.05); and vacuuming, 2.7 +/- 0.7 and 2.9 +/- 0.5Mets. The results indicate that there is a tendency for the metabolic and hemodynamic responses to BTE work simulator tasks to be lower than that of the actual activity. PMID- 8466426 TI - Active or passive physiotherapy for occupational cervicobrachial disorders? A comparison of two treatment methods with a 1-year follow-up. AB - In this study 169 female office employees were interviewed and examined to determine the occurrence and severity of neck and shoulder symptoms. Forty-seven of those with symptoms who fulfilled the criteria taken as indicating need for treatment were enrolled in a controlled clinical trial and divided into two groups. One group participated in dynamic muscle training of neck and shoulder muscles (active physiotherapy). The other patients were treated by means of surface heat, massage, and stretching (passive physiotherapy). Pain in the neck and shoulder regions disappeared significantly more often just after active treatment as compared to passive treatment. Symptoms returned within three months in both groups. However, after 12 months, the incidence of headache was significantly less in the group that had received active physiotherapy. Maximal isometric muscle strength in relation to cervical lateral flexion and extension and grip strength and endurance force of shoulder muscles improved significantly after active physiotherapy, but only maximal isometric extension force increased significantly after passive physiotherapy. Numbers of tender points in neck and shoulder muscles decreased significantly after both types of physiotherapy. Pressure threshold levels increased but not significantly in both groups during treatment. PMID- 8466427 TI - Increasing the wearing time of vinyl urinary drainage bags by decontamination with bleach. AB - The purpose of this study was to determine the safety of 4 week re-use of vinyl urinary leg and bed bags in the acute rehabilitation setting when decontaminated daily with a dilute bleach (sodium hypochlorite) rinse. Patients requiring urinary bags (n = 54) were randomly assigned to Control (C) and Experimental (E) groups. C's bags were replaced weekly; E's only after four weeks. Both groups received identical daily bag decontamination and weekly urine and bag cultures. No significant differences were found between groups with ANCOVA, controlling for baseline urine cultures, age, number of days catheterized, and use of antibiotics. Thirty different organisms were cultured in urine and bags; when the procedure was done daily, all bag cultures showed only minimal contamination (0 100CFU/mL). Bacterial growth (4.4% of leg bags) > 100CFU/mL was found only when the daily decontamination procedure had been omitted. In fact, 57% of leg bags and 76.5% of bed bags returned with no growth. We conclude that it is safe and cost effective to reuse vinyl urinary leg and bed bags for four weeks. PMID- 8466428 TI - Rebox: an adjunct in physical medicine? AB - Electrical therapy is used extensively in the treatment of musculoskeletal diseases. The best known form is transcutaneous electrical nerve stimulation (TENS). Rebox is another apparatus for electrical therapy that operates on much lower currents than TENS (0 to 300 microA). The effect of Rebox was tested on chronic lateral epicondylitis in 16 patients in a controlled crossover study. We found a significant effect of Rebox compared to placebo in respect to all the subjective and the objective variables: grip-strength, pain at power-grip and lifting a weightload with pronated forearm, and daily impairment. PMID- 8466429 TI - The Vannini-Rizzoli orthosis: a unique case of thoracic outlet syndrome. AB - The Vannini-Rizzoli boot is a stabilizing orthosis that allows selected spinal cord injured patients to stand and ambulate. The body positioning required to maintain stability while using these boots can result in an exaggerated "military position" of the shoulders, as the patient braces his shoulders posteriorly to maintain his center of gravity anterior to the ankle axis. This posture produced thoracic outlet compression in this patient. This case emphasizes the need to be aware of this clinical complex when working with this orthosis and suggests the importance of the patient's functional needs in treatment decisions. PMID- 8466430 TI - Drug-induced dysphagia. AB - Dysphagia is a problem commonly treated and frequently diagnosed on the rehabilitation unit. It can be caused by trauma, injury, or diseases of the nervous system and can result in potentially serious and life threatening complications. The disruption of normal swallowing has also been reported to occur in psychiatric patients treated with psychotropic medication. Relatively unappreciated by physicians, and unreported by the rehabilitation patient, drug induced dysphagia can likewise result in serious complications. This report describes a case of drug-induced dysphagia and aspiration pneumonia during the rehabilitation of a traumatically brain injured male who received psychotropic medication to control aggressive behavior. The course of his dysphagia was followed and documented both clinically and with videofluoroscopic studies. PMID- 8466432 TI - The high cost of asthma: a challenge to all GPs. PMID- 8466431 TI - Bracing for serratus anterior palsy. PMID- 8466433 TI - Dislocations in the upper limb. Traps, tricks and treatment. AB - Dislocations in the upper limb are not always straightforward--they are often poorly diagnosed and managed. Careful examination to detect the total injury and awareness of the pitfalls should ensure that mistakes are avoided. PMID- 8466434 TI - Common pitfalls and the treatment of fractures. AB - In summary, the management of fractures is not easy. The clinician must be familiar with fractures and their management and their potential complications. If the problem appears to be outside the scope of a doctors training, it is best referred earlier rather than later. PMID- 8466435 TI - Stress fractures. AB - Stress fractures are now common. They are often missed because the doctor fails to keep the possible diagnosis in mind, or believes that a plain X-ray can exclude these fractures. A bone scan gives the diagnosis. Treatment is by rest in most cases, but stress fractures of the navicular sometimes require surgery. PMID- 8466436 TI - Fractures and dislocations of fingers and toes. Principles, tips and pitfalls. AB - If each injury is carefully assessed on its merits good outcomes will be achieved. If any kind of unusual situation is met advice should be sought early rather than late. Balancing competing concepts, especially with regard to mobilisation and immobilisation of the injured part, makes treatment of digital injuries a challenge to our ingenuity. PMID- 8466437 TI - Understanding insomnia. AB - Anxiety and depression are common causes of insomnia, but they are not the only causes. Neurological disorders such as restless legs syndrome and periodic limb movement disorder are also common. A conceptual model of sleep and wakefulness helps to explain different kinds of insomnia. PMID- 8466438 TI - Helping patients to sleep better without drugs. AB - A brief description of the programme to treat insomnia has been presented. Sleep Better Without Drugs is a comprehensive integrated programme that includes more than 30 elements. One segment of the programme, the nine sleep rules, is presented in the Patient Education feature of this issue. PMID- 8466439 TI - Morbidity and treatment in general practice in Australia. AB - More detailed analysis of this data will continue. It will be combined with other more specific studies to provide a more focused view of some aspects of general practice. Requests for individual analyses of selected data will be accepted by the Family Medicine Research Unit. Contact Helena Britt on (02) 745 2633. The Unit has provided Australian Family Physician with 500 copies of the full report for distribution to interested practitioners. Such copies can be obtained by contacting Mrs Judy Brook, Secretary, Australian Family Physician, 2nd Floor, 70 Jolimont Street, Jolimont 3002. Fax: (03) 289 1211. Telephone: (03) 654 3000. PMID- 8466440 TI - The old painful knee trap. PMID- 8466441 TI - Coronary risk factors, knowledge and beliefs in 'blue collar' men attending general practice. AB - OBJECTIVE: To describe risk factors, dietary knowledge and beliefs in Australian born males of low socio-economic status (SES) in relation to coronary heart disease. METHODOLOGY: Cross-sectional prevalence survey of 180 (99.7% of 185) selected attenders at a community health centre with a high proportion of low SES residents in Melbourne. RESULTS: Mean BMI and prevalence of obesity and smoking were higher than in national sample; age-weighted serum cholesterol somewhat lower. A majority believed that their diets were unhealthy and would continue to be so despite high perceived susceptibility to CHD. Seventy-two per cent wanted more dietary information and GPs were the most commonly nominated preferred source for this information. CONCLUSION: GPs have an important role in targeting this 'at risk' group in order to address the knowledge gaps and misconceptions identified in the study and to encourage appropriate behaviour and risk factor modification. PMID- 8466442 TI - Night call to the dead. PMID- 8466443 TI - Dr. Paul Nisselle. GPs' defence counsel. PMID- 8466444 TI - Marsupialisation technique for Bartholin's cyst. PMID- 8466445 TI - Working birthdays. PMID- 8466446 TI - The right to know--the need to disclose. AB - The High Court judgment states explicitly that your duty to disclose will now be measured by a legal standard. Gaudron J states: "... there is simply no occasion to consider the practice or practices of medical practitioners in determining what information should be supplied ..." Thus the court in dismissing the appeal has moved substantially to the American position, which emphasizes the right of the patient to make up his or her own mind in the light of the relevant circumstances and the right of the patient to know about material risks, "a right which in turn arises from the patient's right to decide for himself or herself whether or not to submit to the medical treatment proposed". In short, a prudent GP, in the light of this High Court judgment, will talk more, and will write down what has been said. PMID- 8466447 TI - Logistics of participation in clinical trials. AB - A decision to participate in a clinical drug trial will require a commitment in time and resources from both the doctor and other practice staff. The authors explain some of the strategies that can be used to maximise the limited time available for such research and minimise unnecessary wastage of scarce resources. PMID- 8466448 TI - Identifying the warts in your practice. PMID- 8466449 TI - Patient education. Nine rules for better sleep. PMID- 8466450 TI - The use of calcium channel blockers in general practice. AB - Over the past decade the calcium antagonist drugs, also known as calcium channel blockers, have become established for use in a variety of cardiovascular diseases. A bewildering (and ever-growing) number of drugs in this class now becoming available. This article summarises the important characteristics of the calcium antagonists and discusses their practical use in hypertension, angina and other conditions in general practice. PMID- 8466451 TI - Future access to Medline. PMID- 8466452 TI - Laparoscopic ultrasonography. PMID- 8466453 TI - Small area analysis of lumbar spine surgery in South Australia. AB - The hospital separation records for 1987 in the health planning regions of South Australia were reviewed using a selection algorithm to identify all hospitalizations involving a lumbar spine surgery (LSS) for low back or leg pain. Among 16 health planning regions (two additional regions were excluded from the analysis because of the low number of observations) the LSS rate varied almost four-fold, from 25 to 92/100,000, with a mean of 55/100,000. The effect of 24 socioeconomic and health care supply characteristic variables upon observed differences in rates were tested. The unemployment rate was the only significant variable in the analysis, explaining 11% of the variation in the surgery rates for the 16 regions. This finding is in agreement with studies from other countries that suggest that characteristics of small areas do not substantially predict the rates of elective surgical procedures. The decision-making processes of surgeons and their patients remain poorly defined; the contributions to the rate of lumbar spine surgery by the health care delivery system, physician behaviours or patient expectations are not yet identified. PMID- 8466454 TI - Impact of pedestrian injury on inner city trauma services. AB - This report describes the epidemiology of pedestrian injury in four inner metropolitan local government areas of Sydney. These data were obtained from the Roads and Traffic Authority of New South Wales. The spectrum of injury and clinical outcome was defined in patients with an Injury Severity Score (ISS) > 15 admitted from the study area, during a 1 year period, to the four inner metropolitan teaching hospitals. The incidence of pedestrian death was 3.3 times the state average of 32/10(6)/year. An average of 235 pedestrians, injured in the study area, were hospitalized each year during the period 1987-89. On average 24 pedestrians died each year, seven at the scene and 17 in hospital. Fifty patients (ISS > 15) were admitted to the four teaching hospitals during a 1 year period 1990-91. Forty-five were adults and five children. Multiplicity of injury was seen in 68% of patients. The pelvis and lower extremities were involved in 70%, the head in 66% and chest in 42%. The hospital mortality rate was 30% with five patients dying on the first day from blood loss and nine dying during subsequent days from head injury. This study has important implications for trauma service development. Successful clinical management of the severely injured pedestrian requires close co-operation between pre-hospital and hospital care providers. An integrated hospital trauma team response is mandatory to ensure appropriate management of what is often a shocked, hypoxic, head-injured patient. PMID- 8466455 TI - The management of renal cell carcinoma with inferior vena-caval involvement. AB - Seven patients with renal cell carcinoma involving the inferior vena cava underwent surgical resection between 1975 and 1991. Pre-operative staging defined five patients with stage T3bNoMo disease, one patient with stage T3bN1Mo, and one patient with stage T3bNoM1 disease. At operation one patient had tumour thrombus filling the right atrium. Two patients had tumour thrombus within the intrahepatic vena cava and four infrahepatic tumour thrombus. The mean follow-up is 34.4 months (median 40 months). Four patients have been followed for over 4 years. Three of these patients are survivors, two have remained disease-free since their initial surgery. The other patient had a liver resection at 49 months for a solitary metastases; he is currently disease free. One patient died at 38 months from a gastrointestinal haemorrhage. Three patients are 12 months or less postoperation. Operative mortality was zero. The mean postoperative hospital stay was 14.7 days. Data suggests that 3-10% of renal cell carcinomas will involve the inferior vena cava. The small number of patients in this series suggests that many patients with renal cell carcinoma involving the inferior vena cava are not referred for surgical assessment. These patients are potential surgical candidates. Their survival after surgical resection, excluding the group with extension of tumour thrombus into the hepatic cava or above, is not reduced when compared with other patients with renal carcinoma. PMID- 8466456 TI - The role of ERCP and endoscopic sphincterotomy in the era of laparoscopic cholecystectomy. AB - The advent of laparoscopic cholecystectomy (LC) has led to some controversy regarding the best method of managing bile duct calculi. This paper reviews the cases of 38 patients who underwent LC and endoscopic retrograde cholangiopancreatography (ERCP), from a series of 600 consecutive laparoscopic cholecystectomies. Twenty-nine patients had ERCP performed pre-operatively because of suspicion of choledocholithiasis. Duct stones were confirmed in eight patients. Recent or current jaundice was the best predictor of bile duct stones. Nine patients had ERCP done postoperatively because of duct stones seen on operative cholangiography. In two patients bile duct cannulation was not possible and a third procedure, open duct exploration, was necessary. Techniques in laparoscopic management of duct stones are improving and the role of ERCP and sphincterotomy should be limited to jaundiced patients or those with proven bile duct stones in whom laparoscopic procedures have been unsuccessful. PMID- 8466457 TI - Primary cerebral lymphoma: an argument for the use of adjunctive systemic chemotherapy. AB - Eleven patients with primary cerebral lymphoma were treated at a single institution over a 5 year period. Patient characteristics were typical of this rare disease. One patient died prior to receiving treatment and of the remaining 10, all received cranial irradiation and in addition, five received systemic cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) chemotherapy. Of the six patients who are alive and disease-free, five received the combined modality therapy. The median survival for those patients receiving cranial irradiation alone was 18 months and for the combined modalities was 25+ months. Combination systemic chemotherapy, in addition to cerebral irradiation, may convey a survival benefit in patients with primary cerebral lymphoma but this requires further investigation with multicentre, prospective randomized trials. PMID- 8466458 TI - Primary central nervous system tumours in Australia: a profile of clinical practice from the Australian Brain Tumour Register. AB - An epidemiological survey of all primary central nervous system tumours in Australia was commenced in 1986. Cases was reported by the treating physician to the Australian Brain Tumour Register, located at the Victorian Cancer Registry. Ninety-three per cent of tumours were histologically confirmed and 69% were reviewed by an independent pathology panel. During the initial 3 years of the survey a total of 4577 brain tumours and 266 primary spinal cord tumours were reported to the Register. The age standardized rates for malignant tumours of the central nervous system, sum to 5.0/100,000 males and 3.4/100,000 females. Twenty eight per cent of gliomas were biopsied only. Radiotherapy was administered to 57% of cerebral gliomas and 2% of these tumours were treated with adjuvant chemotherapy. Forty per cent of meningiomas were considered to have had a complete tumour resection. PMID- 8466459 TI - Laparoscopic management of acute small bowel obstruction. AB - Acute small bowel obstruction is commonly due to band adhesions. In the past it has had an overall mortality rate of up to 11% for elderly patients. In this paper we report three cases of small bowel obstruction, treated by laparoscopic division of the causative bands. All patients recovered rapidly and were discharged within 5 days of surgery. PMID- 8466460 TI - A (more) simple technique for locating the umbilicus in abdominoplasty. AB - A method for simply and accurately locating the umbilicus in abdominoplasty is described. The method uses a shaped wire and ink. PMID- 8466461 TI - The evaluation of the isolated perfused liver as a model for the assessment of liver preservation. AB - An ex vivo isolated perfused porcine liver model was tested to assess its suitability for rapid, reliable and relatively cheap testing of organ preservation solutions for liver transplantation. The model consists of a machine driven recirculating system incorporating an organ chamber, blood pump and membrane oxygenator. Autologous blood was used for perfusion for a period of 2 h at a temperature of 37 degrees C. The model was tested with five groups of livers which had sustained varying degrees of injury ranging from minimally damaged to those known to be incapable of sustaining life when used for liver transplantation. The groups of livers were: (i) controls; (ii) preserved in University of Wisconsin solution (UW) for 6 h; (iii) preserved in an albumin based extracellular fluid (ALB) for 6 h; (iv) preserved in UW for 18 h; and (v) preserved in ALB for 18 h. Bile production was found to be a reliable parameter of preservation damage. Changes in perfusate levels of aspartate aminotransferase, potassium, glucose and calcium also occurred in relationship to preservation damage. In contrast, weight gain of the liver, sequestration of the white cells and platelets in the liver, urea production and oxygen consumption were unreliable predictors of liver damage. Histology of biopsy specimens revealed apparently well preserved livers in all cases after preservation but before perfusion, but serious abnormalities after perfusion in long preserved livers, with features in these suggestive of damage to the sinusoidal endothelium. We believe that the model is a worthwhile adjunct to research into liver preservation. PMID- 8466462 TI - Retention of surgical knowledge base by senior medical students. AB - The medical course at the University of Queensland is 6 years in length. After studies in basic sciences, the fourth year consists of systematic pathology, clinico-pathological correlation and the learning of clinical methods. During the fifth year the core surgical knowledge base is taught. The sixth year is spent in clinical ward work aimed at problem-orientated consolidation of knowledge and skills, and the learning of applied therapeutics. We studied whether the surgical knowledge base taught to our fifth year students was retained a year later by the same students in their final year. A standardized post-test examination which had been presented to the students during their fifth year in 1990 was again presented to them during their sixth year in 1991. We found that the surgical knowledge base of this group of students remained the same in their final year as it had been in their penultimate year. We suggest that to continue testing core surgical knowledge once it has proven satisfactory is not productive. These students should progress to further clinical studies aimed at improving their problem solving ability. PMID- 8466463 TI - Carl Langenbuch and the Lazarus Hospital: events and circumstances surrounding the first cholecystectomy. AB - Carl Langenbuch performed the first cholecystectomy at the Lazarus Hospital in Berlin in July 1882. This operation followed scientific experiment, careful thought, cadaver dissections and careful patient selection. Langenbuch's career was linked with the Lazarus Hospital in Berlin, to which he was appointed as Director at the age of 27. The hospital was then 4 years old and in a poor area of Berlin, and they grew in reputation together. Going through repeated troubled times, this hospital has withstood financial disaster, three wars, an occupation and the ambitions of administrators and developers. Treatment for cholecystitis before Langenbuch was stone extraction from spontaneous cutaneous biliary fistula or skin incision of near-pointing empyema. Cholecystostomy was carried out by Bobbs (1867), by Sims (1878), and championed by Kocher (1878) and Tait (1879). Langenbuch carried out a cholecystectomy in 1882 and subsequently recommended choledochotomy, duodenotomy and sphincterotomy in the management of stones in the bile ducts. He carried out one of the earlier major right liver resections in 1888. Also, he was famous for his sciatic nerve stretching for tabes dorsalis, management of gunshot wounds and his dissertations at the German Surgical Society before becoming renowned for cholecystectomy. The surgical world owes Langenbuch proper acknowledgement for his contribution to hepatobiliary surgery. PMID- 8466464 TI - A rare cause of acute aortic occlusion. PMID- 8466465 TI - Misdiagnosis of appendicitis in tubally sterilized women. AB - Sterilization by tubal occlusive methods has a small but definite incidence of failure which is not well recognized among general surgeons. As a result of the failure to appreciate the possibility of ectopic pregnancy after tubal ligation, right-sided abdominal pain in this patient population is commonly misdiagnosed as appendicitis. One such case is presented, and the literature is reviewed and discussed. PMID- 8466466 TI - Delayed epididymitis following intravesical bacillus Calmette-Guerin administration. PMID- 8466467 TI - Intra-aortic balloon rupture causing femoral entrapment. AB - Rupture of an intra-aortic balloon counterpulsator (IABCP) demands immediate removal. We report a case of thrombus formation within a Datascope IABCP secondary to IABCP rupture, necessitating surgical exploration for removal. There is a disturbing pattern of balloon ruptures with this type of IABCP. PMID- 8466468 TI - Neutropenic enterocolitis treated by primary resection with anastomosis in a leukaemic patient receiving chemotherapy. AB - Neutropenic enterocolitis is a complication of patients receiving chemotherapy for malignant disease. It has a characteristic presentation and may lead to gut perforation with consequent high mortality. It is best treated by early surgical intervention. Considerable mortality is inevitable in these gravely ill patients. PMID- 8466469 TI - Right chylothorax following left radical neck dissection. AB - The development of a right chylothorax following left radical neck dissection for melanoma is reported. Chylothorax following neck dissection is extremely rare, with only 12 cases documented in the literature. Seven of these were bilateral and three were unilateral (all left-sided); unilateral right chylothorax after neck dissection has not been reported previously. Chylothorax is more common after intrathoracic surgery or trauma. Regardless of its cause, the condition is potentially serious and sometimes fatal. Our patient was successfully managed without further surgery. The aetiology and management of chylothorax following neck dissection are discussed. PMID- 8466470 TI - Development and organizational structure of an acute pain service in a major teaching hospital. AB - Pain management is an essential part of postoperative care. The present availability of multiple modalities of patient controlled and continuous regional analgesia requires the reorganization of existing hospital structures to be efficacious and safe. This article presents an Acute Pain Service (APS) as a model for a reorganized structure. Although anaesthesia based, this service requires close co-operation of surgeons, nurses and other paramedical personnel to achieve the expected results. Prerequisites of an APS are careful selection of suitable techniques as well as the formulation of protocols and standing orders for the techniques. Inservice training of involved personnel, dedicated single ward trials and introduction of the revised technique for general use are further essential steps in its development. The organizational structures proposed include selection of the appropriate technique for a patient by the theatre anaesthetist, preparation and documentation by the recovery nurse, monitoring and ongoing skilled assessment by the ward nurse and ward rounds, advice and 24 h availability by anaesthetists. PMID- 8466471 TI - What determines whether chromosomes segregate reductionally or equationally in meiosis? AB - Normal meiosis consists of a single round of DNA replication followed by two nuclear divisions. In the 1st division the chromosomes segregate reductionally whereas in the 2nd division they segregate equationally (as they do in mitosis). In certain yeast mutants, a single-division meiosis takes place, in which some chromosomes segregate reductionally while others divide equationally. This autonomous segregation behaviour of individual chromosomes on a common spindle is determined by the centromeres they carry. The relationship between reductional segregation of a pair of chromosomes and their earlier recombinational history is also discussed. PMID- 8466472 TI - Exploitation of host signal transduction pathways and cytoskeletal functions by invasive bacteria. AB - Many bacteria that cause disease have the capacity to enter into and live within eukaryotic cells such as epithelial cells and macrophages. The mechanisms used by these organisms to achieve and maintain this intracellular lifestyle vary considerably, but most mechanisms involve subversion and exploitation of host cell functions. Entry into non-phagocytic cells involves triggering host signal transduction mechanisms to induce rearrangement of the host cytoskeleton, thereby facilitating bacterial uptake. Once inside the host cell, intracellular pathogens either remain within membrane bound inclusions or escape to the cytoplasm. Those living in the cytoplasm can further pirate the host actin system, using actin as a mechanism to facilitate movement within and between host cells. Organisms remaining within the vacuole have specialized mechanisms for intracellular survival and growth which involve additional communication with the host cell. Some of the processes involved in the various steps of facultative intracellular parasitism are discussed in the context of subverting the host cell cytoskeleton and signal transduction pathways for bacterial benefit. PMID- 8466473 TI - Bending of DNA by transcription factors. AB - An increasing number of transcription factors both from prokaryotic and eukaryotic sources are found to bend the DNA upon binding to their recognition site. Bending can easily be detected by the anomalous electrophoretic behaviour of the DNA-protein complex or by increased cyclization of DNA fragments containing the protein-induced bend. Induction of DNA bending by transcription factors could regulate transcription in various ways. Bending may bring distantly bound transcription factors closer together by facilitating DNA-looping or it could mediate the interaction between transcription factors and the general transcription machinery by formation of large nucleoprotein structures in which the DNA is wrapped around the protein complex. Alternatively, the energy stored in a protein-induced bend could be used to favour formation of an open transcription complex or to dissociate the RNA polymerase in the transition from initiation to elongation. Modification of the bend angles and bending centers, caused by homodimerization or heterodimerization of transcription factors, may well turn out to be an important way to enlarge the range of interactions required for regulation of gene expression. PMID- 8466474 TI - RNA editing: exploring one mode with apolipoprotein B mRNA. AB - RNA editing is a newly described genetic phenomenon. It encompasses widely different molecular mechanisms and events. According to the specific RNA modification, RNA editing can be broadly classified into six major types. Type II RNA editing occurs in plants and mammals; it consists predominantly in cytidine to uridine conversions resulting from deamination/transamination or transglycosylation, although in plants other mechanisms have not been excluded. Apolipoprotein B mRNA editing is the only well-documented editing phenomenon in mammals. It is an intranuclear event that occurs posttranscriptionally, coincident with splicing and polyadenylation. Recent observations indicate that the tissue- and sequence-specific process is mediated by an enzyme that has separate domains for editing and sequence recognition. The presence of apolipoprotein B mRNA editing activity in tissues that do not produce the protein suggests that other RNAs may be edited and RNA editing may be a genetic phenomenon of general biological importance to the cell. PMID- 8466475 TI - Interaction of rhodopsin with the G-protein, transducin. AB - Rhodopsin, upon activation by light, transduces the photon signal by activation of the G-protein, transducin. The well-studied rhodopsin/transducin system serves as a model for the understanding of signal transduction by the large class of G protein-coupled receptors. The interactive form of rhodopsin, R*, is conformationally similar or identical to rhodopsin's photolysis intermediate Metarhodopsin II (MII). Formation of MII requires deprotonation of rhodopsin's protonated Schiff base which appears to facilitate some opening of the rhodopsin structure. This allows a change in conformation at rhodopsin's cytoplasmic surface that provides binding sites for transducin. Rhodopsin's 2nd, 3rd and putative 4th cytoplasmic loops bind transducin at sites including transducin's 5 kDa carboxyl-terminal region. Site-specific mutagenesis of rhodopsin is being used to distinguish sites on rhodopsin's surface that are important in binding transducin from those that function in activating transducin. These observations are consistent with and extend studies on the action of other G-protein-coupled receptors and their interactions with their respective G proteins. PMID- 8466476 TI - Mechanism of action of the Escherichia coli UvrABC nuclease: clues to the damage recognition problem. AB - During the process of E. coli nucleotide excision repair, DNA damage recognition and processing are achieved by the action of the uvrA, uvrB, and uvrC gene products. The availability of highly purified proteins has lead to a detailed molecular description of E. coli nucleotide excision repair that serves as a model for similar processes in eukaryotes. An interesting aspect of this repair system is the protein complex's ability to work on a vast array of DNA lesions that differ widely in their chemical composition and molecular architecture. Here we propose a model for damage recognition in which the UvrB protein serves as the component that confers enhanced specificity to a preincision complex. We hypothesize that one major determinant for the formation of a stable preincision complex appears to be the disruption of base stacking interactions by DNA lesions. PMID- 8466477 TI - Do specific interactions between transmembrane helices play a part in signalling transduction? Exploration with the insulin receptor. PMID- 8466478 TI - The pharmacological manipulation of members of the transforming growth factor beta family in the chemoprevention of breast cancer. AB - The transforming growth factors beta are a family of peptides which are involved in the regulation of cell growth and differentiation. It has been suggested that the loss of sensitivity to growth inhibition by endogenous TGF-beta may contribute to the process of carcinogenesis in epithelial systems. However, many breast cancer cells remain sensitive to the growth inhibitory effects of these peptides, suggesting that the local induction of TGF-beta could provide a pharmacological approach to chemoprevention. Triphenylethylene anti-oestrogens, synthetic progestins and retinoids all offer potential as chemopreventative agents. A common feature of their mechanism of action is the ability to locally increase the production of the transforming growth factors beta. PMID- 8466479 TI - Biochemical characterization of a protein inhibitor for DNA ligase I from human cells. Regulation/replication/repair/recombination. AB - An inhibitor for DNA ligase I has recently been purified from human cells. This inhibitor of 55-75 kDa forms a reversible complex with DNA ligase I, but has no effect on DNA ligase II and T4 DNA ligase, suggesting that it may play a regulatory role for DNA replication and repair. This report shows that the inhibitor was sensitive to heating at 52 degrees C and to trypsin treatment, indicating that it is a heat-labile protein. The inhibitor affected the ligation of double- and single-strand breaks in natural and synthetic DNA, but had no effect on the formation of the ligase-AMP complex and on the subsequent reaction following the formation of the AMP-DNA complex. These data indicate that the major mechanism of action for the inhibitor is the blocking of the second step of the reaction, in which the AMP moiety is transferred from the ligase-AMP to DNA. The site of interaction for the enzyme is therefore localized in a domain associated with the DNA binding or the AMP-transferring function. PMID- 8466480 TI - IL-1 beta decreases expression of amyloid precursor protein gene in human glioma cells. AB - In Alzheimer's disease a small fragment of the amyloid protein precursor (APP), called beta 4, is a characteristic component of senile plaques in brains of affected patients. Efforts to intervene in Alzheimer's disease include approaches by which APP levels can be decreased in brain. The study described here demonstrates the expression of APP gene in four cell lines that originated from human brain glioblastomas. In one line, HTB 17, APP mRNA level was approximately 25% the APP mRNA found in human brain and 150% that found in human liver. To ascertain whether or not APP expression in HTB 17 cells could be modulated by a cytokine associated with the inflammatory response, cells were cultured in the presence of IL-1 beta. A significant decrease in APP mRNA accompanied treatment of glioma cells with IL-1 beta. PMID- 8466481 TI - Dopamine D1 receptor mutagenesis: role of amino acids in agonist and antagonist binding. AB - We investigated the role of amino acids, by site-directed mutagenesis, in five of the seven transmembrane regions of the human dopamine D1 receptor. The results demonstrate a role for an aspartic acid (Asp70) in transmembrane 2 mediating the sodium ion effect on receptor conformation. Amino acids residues in transmembrane 3 and 5 are important for optimum dopamine binding to the receptor. Mutant receptors involving amino acids in transmembrane 7 suggest that binding sites for agonists and antagonists have distinct binding determinants within the dopamine D1 receptor. PMID- 8466482 TI - Cloning of a variant epidermal growth factor receptor. AB - The sequences encoding the full-length epidermal growth factor receptor (EGFR) were cloned from a cDNA library prepared from T3M4 cells. A transition (G to A) was identified at codon 497 of EGFR cDNA, resulting in the substitution of a lysine for an arginine. The same substitution was identified by sequencing cDNA derived from 3 of 7 additional human pancreatic cancer cell lines, one endometrial cancer cell line, and one lung cancer cell line, but not in A431 cells. Variant EGFR was always co-expressed with wild-type EGFR. Both sequences were present in genomic DNA from two cell lines expressing the variant receptor and in DNA from normal (3 of 7 individuals) human lymphocytes. These findings indicate that there are two alleles in this region of the EGFR gene, and that expression of variant EGFR is a common occurrence in normal and cancerous cells. PMID- 8466483 TI - Regulation of the rat class I alcohol dehydrogenase gene by growth hormone. AB - Growth hormone (GH) increases the transcription of the rat class I alcohol dehydrogenase (ADH) gene. Two transcription factors, the CCAAT/enhancer binding protein (C/EBP) and the liver activator protein (LAP), were previously shown to bind to the ADH promoter at nucleotide positions -11 to -22 relative to the start site of transcription and to activate the ADH promoter in co-transfection experiments. In this study, exposure of cultured rat hepatocytes to GH (1 micrograms/ml) for 4 days increased LAP mRNA, but not C/EBP mRNA, in conjunction with an increase in ADH mRNA. GH, in transient transfection experiments of primary rat hepatocyte cultures, activated an ADH promoter-reporter gene construct containing the C/EBP binding site, but failed to activate a construct containing a 4-bp mutation at this site. These results suggest that the effect of GH in enhancing ADH promoter activity is mediated by LAP binding to the C/EBP site. PMID- 8466484 TI - Enzymatic labeling of biologically active envelope glycoprotein gp120 of HIV-1. AB - We have found that the envelope glycoprotein gp120 of HIV-1 can be modified extensively by enzymatic oxidation of oligosaccharide chains without diminishing binding to its natural receptor, CD4. Using affinity purified galactose oxidase, over 20 sites per gp120 molecule were converted to chemically reactive aldehydes, as measured by 3H-BH4 reduction, while the conformation-dependent CD4 binding site remained intact. In contrast, periodate oxidation completely destroyed CD4 binding while producing fewer sites. Enzymatically labeled, biologically active gp120 should facilitate biochemical studies of receptor binding and viral inactivation by neutralizing antibodies. PMID- 8466485 TI - Endothelin-1 and endothelin receptor mRNA expression in normal and atherosclerotic human arteries. AB - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide implicated in a number of human diseases including atherosclerosis. ET-1 binds to two distinct G protein coupled receptors, known as the ETA and ETB receptor subtypes. In this study, we have examined ET-1, ETA and ETB mRNA expression levels in human vascular cells cultured in vitro and in normal and atherosclerotic human arteries. The results indicate that (a) ET-1 mRNA is constitutively expressed by endothelial cells but not by smooth muscle cells, (b) endothelial cells express only ETB mRNA but smooth muscle cells co-express ETA and ETB mRNA, and (c) in comparison to normal aorta, ET-1 mRNA expression is elevated and endothelin receptor mRNA expression is repressed in atherosclerotic lesions. PMID- 8466486 TI - Purification and characterization of three MEKA-like proteins in liver: association of a 94 kDa protein with beta gamma subunits of G-proteins. AB - Retinal 32 kDa MEKA protein (rMEKA) exists in the photoreceptor cells and forms a complex with beta gamma subunit of transducin. Bovine liver contained three MEKA like proteins (94 kDa, 35 kDa-a, 35 kDa-b) which reacted with a rMEKA antibody. Each protein was purified as a single band on a SDS-PAGE and used for a reconstitution experiment with alpha and beta gamma subunits of cerebral G proteins (Go/i). The 94 kDa protein inhibited GTP-binding ability of G alpha by forming a complex with beta gamma subunit. PMID- 8466487 TI - The monosialoganglioside GM1 induces internalisation and degradation of the CD4 antigen in U937 cells: evidence for a novel mechanism of CD4 down-modulation in a p56lck-negative cell line, which is independent of protein kinase C activation. AB - Sialated glycosphingolipids (gangliosides) were recently shown to induce internalisation of the CD4 Ag in lymphoid cells and dissociation of p56lck from CD4 (Repke et al. (1992) J. Immunol. 149, 2585-2591; Saggioro et al. (1993) J. Biol. Chem. 268, 1368-1375). The findings presented in this paper show that GM1 induces internalisation and the eventual degradation of the CD4 Ag also in the monocytic cell line U937. GM1 effects are independent of a possible activation of protein kinase C, as enzyme inhibitors which effectively blocked phorbol esters effects did not prevent GM1-induced CD4 internalisation and degradation. GM1 effects were also independent of a possible action on a CD4 associated kinase activity as we show that U937 cells lack any CD4-associated kinase activity. PMID- 8466488 TI - Evidence for a dual osmoregulatory mechanism in the yeast Saccharomyces cerevisiae. AB - Osmoadaptation in S. cerevisiae occurs through intracellular accumulation of glycerol in response to an increase in osmolarity of the surrounding environment. Analysis of ssv1-2, a strain carrying a mutation in a gene required for vacuole biogenesis, protein-sorting and osmohomeostasis, shows that the strain is terminally inactivated by 1.5 M NaCl within 10 seconds while the isogenic wild type maintains slow growth and accumulates glycerol within 18 hours. This study provides the first evidence that the vacuole participates in an immediate osmoregulatory process permitting survival until the osmoadaptive glycerol accumulation allows growth under osmotically unfavorable conditions. PMID- 8466489 TI - Detection of beta-thalassemia carrier by direct analysis of beta-globin gene lesions. AB - DNA was prepared from peripheral blood mononuclear cells of 114 Chinese with low erythrocyte mean corpuscular volume and analyzed by allele-specific DNA amplification for the presence of mutant alleles in the beta-globin gene that account for about 90% of beta-thalassemia in Chinese. A total of 9 mutations of the five most frequent mutant alleles were detected in 8 individuals. All mutant sequences were confirmed later by DNA sequencing. However, no mutation of these mutant alleles was detected in the remaining 106 individuals with low erythrocyte mean corpuscular volume including 22 who also had Hb A2 content of 6.0% or more. Our results seem to suggest that the presence of beta-thalassemia allele does not correlate very well with red blood cell indices and that direct DNA analysis by allele-specific DNA amplification is an accurate method to identify beta thalassemia heterozygotes. PMID- 8466490 TI - Biochemical and immunological characterization of calcium-dependent and independent PKC isoenzymes in renal ischemia. AB - The PKC alpha, beta, delta, epsilon and zeta isoenzyme changes in the rat kidney cortex have been investigated after temporary occlusion of the renal artery, followed by reperfusion for up to 4 h. Increased PKC alpha, delta and epsilon immunoreactivity and PKC alpha activity occurred within 60 min of postischemic reflow, while PKC beta and zeta were unmodified. Increased PKC beta activity was present at later times of reflow (120 min), suggesting that the initial events of the regenerative repair response after an ischemic insult implicate the activation of specific PKC isoenzymes (alpha, delta, epsilon), playing a role in the control of cell proliferation. PMID- 8466491 TI - Expression of non-ADP-ribosylatable, diphtheria toxin-resistant elongation factor 2 in Saccharomyces cerevisiae. AB - Eucaryotic elongation factor 2 (EF-2) contains a post-translationally modified histidine residue termed diphthamide that is specifically ADP-ribosylated by diphtheria toxin (DT) or Pseudomonas exotoxin A. To analyze the potential physiological role of ADP-ribosylation of EF-2 by cellular ADP-ribosyl transferase, we constructed DT-resistant, non-ADP-ribosylatable Saccharomyces cerevisiae EF-2 by site-directed mutagenesis and expressed the mutant EF-2 in yeast. Substitution of Arg for Gly(701) in yeast EF-2 conferred complete resistance to DT in vivo and in vitro. However, when only non-ribosylatable EF-2 was expressed in cells using genetic manipulation, the mutated EF-2 did not affect vegetative cell growth, mating, sporulation and germination of ascospores. PMID- 8466492 TI - Cellular uptake of phosphorothioate oligodeoxynucleotides is negatively affected by cell density in a transformed rat tracheal epithelial cell line: implication for antisense approaches. AB - Antisense oligodeoxynucleotides have been used to specifically inhibit the expression of a variety of genes. In the process of testing phosphorothioate oligodeoxynucleotides (S-oligos) as specific inhibitors of transforming growth factor alpha synthesis, we observed that the efficiency of cellular uptake of S oligos was not constant throughout the culture period but decreased as the cell densities increased. Our data suggest that the mechanism by which oligonucleotides enter cells is negatively affected by increased cell density. These results emphasize the importance of determining uptake kinetics before designing and interpreting antisense experiments using phosphorothioate oligonucleotides. PMID- 8466493 TI - Molecular characteristics of uronic-acid-rich protein, a strong inhibitor of calcium oxalate crystallization in vitro. AB - Uronic-acid-rich protein (UAP) is a new urinary macromolecule which strongly inhibits calcium oxalate crystal formation. It is a glycoprotein with a molecular weight of about 35,000 Da, and its carbohydrate content is 8.5%. This inhibitor is composed of two polypeptidic chains crosslinked by chondroitin sulfate. It exhibits partial structural homology with alpha 1-microglobulin. The inhibitory activity seems to be supported by peptidic chains as determined by enzymatic assay. PMID- 8466494 TI - Crosslink formation between DNA and nuclear proteins by in vivo and in vitro exposure of cells to dimethylarsinic acid. AB - DNA damage induced by arsenics, particularly by dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, was investigated. DNA-protein crosslinks, similarly to DNA single-strand breaks, were induced in mouse and human culture cells by the treatment with DMAA. The crosslinks were sensitive to treatment with guanidine and hydroxylamine, suggesting that the DNA linkage sites in proteins were serine and threonine residues of H1 histone and of nonhistone proteins and that the linkage occurred through a phospho-nitrogen bond. The type of crosslinks was different from that induced by X-ray radiation. Of the radicals produced in the further metabolic processing of DMAA, the dimethylarsenic peroxyl radical rather than the superoxide anion radical is likely responsible for the formation of crosslinks, similar to the case of DNA single-strand breaks. PMID- 8466495 TI - Identification of 34 apolipoprotein(a) isoforms: differential expression of apolipoprotein(a) alleles between American blacks and whites. AB - A total of 34 different apo(a) isoforms was identified in a population sample of 806 American Whites and 701 American Blacks by a high resolution SDS-agarose gel electrophoretic method followed by immunoblotting. Among the 1507 individuals tested, 79% revealed double-banded phenotypes and 21% single-banded phenotypes. The frequencies of the apo(a) isoforms differed between American Blacks and Whites (p < 0.001). PMID- 8466496 TI - The passive calcium leak in cultured porcine aortic endothelial cells. AB - Unidirectional 45Ca fluxes were measured to characterize the calcium-leak pathway in cultured endothelial cells of pig aorta. Lanthanum, but not other calcium channel blockers such as verapamil and diltiazem, inhibited the passive 45Ca uptake. Passive uptake of 45Ca across the plasma membrane increased progressively as extracellular pH was raised from 5.2 to 9.2. SK&F 96365, a putative inhibitor of receptor-mediated Ca2+ entry, selectively blocked ATP-induced 45Ca uptake. The Ca2+ leak pathway may play an important role in endothelial cell Ca2+ homeostasis which controls the basal and stimulated release of endothelium-derived relaxing factors (i.e., EDRF, prostacyclin) in physiological or pathological situations. PMID- 8466497 TI - Role of the collagen-like domain of the human serum mannan-binding protein in the activation of complement and the secretion of this lectin. AB - Human mannan-binding protein (MBP) is a C-type serum lectin involved in an immunoglobulin-independent host defense. Recently, a common defect of immune opsonin was found to be associated with very low serum levels of MBP. This deficiency was thought to be an effect of a single base substitution in the MBP gene, which resulted in the conversion of Gly54 to Asp. In this study, three mutant MBPs were expressed in COS-1 cells and the effects of these mutations were studied. Gly54Asp-MBP and Gly57Asp-MBP were secreted into the medium almost at the same levels as the wild type MBP, but the formation of higher multimers and the activation of complement were interfered with significantly. The other mutant, in which Leu was inserted into the Gly63-Gln-Gly sequence to restore the collagen motif of the Gly-Xaa-Yaa repeat, was secreted at levels similar to that of the wild type, formed higher multimers and activated complement in a manner not significantly altered from that of the wild type. These results are discussed with regard to the molecular basis of patients with opsonic defects. PMID- 8466498 TI - Identification of binding domains on the superantigen, toxic shock syndrome-1, for class II MHC molecules. AB - Toxic shock syndrome toxin-1 (TSST-1) is a member of the staphylococcal enterotoxin superantigen family. In order to determine the regions on the TSST-1 molecule involved in binding to class II MHC, seven overlapping peptides of the entire TSST-1 molecule were synthesized and tested for their ability to compete with 125I-TSST-1 for binding to class II MHC on murine A20 cells and HLA on Raji cells. Peptides corresponding to N-terminal amino acid residues 39 through 68 and C-terminal residues 155 through 194 competed with 125I-TSST-1 for binding to class II MHC. Also, binding studies with class II MHC beta-chain peptides indicate that regions encompassed by I-A beta b(30-60) and I-A beta b(60-90) are binding regions for TSST-1. Thus, we have identified binding domains on the TSST 1 molecule for class II MHC molecule receptors on antigen presenting cells. PMID- 8466499 TI - Stimulation of DNA synthesis in hepatocytes by hepatocyte growth factor bound to extracellular matrix. AB - Hepatocyte growth factor (HGF) purified from human placenta was specifically bound to a component in ECM secreted from lung fibroblasts, hepatocytes, and nonparenchymal liver cells. HGF was also bound to a component in basement membrane matrigel. The rate of DNA synthesis in hepatocytes cultured on the HGF bound ECM was 4-7 times that of control hepatocytes. When ECM-coated dishes were pretreated with heparinase and heparitinase prior to binding of HGF, the stimulation decreased remarkably. A considerable decrease in the stimulation was observed following the washing of HGF-bound ECM with 1 M NaCl. We propose, based on these observations, that HGF bound to the ECM component present in Disse's space functions in regeneration following hepatic injury. PMID- 8466500 TI - Catabolism of intact type VI collagen microfibrils: susceptibility to degradation by serine proteinases. AB - We present the first direct biochemical evidence for the turnover of intact type VI collagen microfibrils. Matrix-degrading enzymes of the serine proteinase class, including rat mast cell chymases I and II, human mast cell tryptase, neutrophil elastase, cathepsin G and trypsin, were able to catabolize intact type VI collagen microfibrils isolated from foetal bovine skin and metabolically labelled intact type VI collagen immunoprecipitated from fibroblast culture medium. By contrast, intact type VI collagen was not degraded by the human matrix metalloproteinases, MMP-1, MMP-2, MMP-3 and MMP-9. These data have important implications for the stability of type VI collagen in connective tissues and highlight the potential role of serine proteinases both in normal type VI collagen turnover and in inflammatory conditions characterized by matrix degradation. PMID- 8466501 TI - Endothelin-1 induces cholestasis which is mediated by an increase in portal pressure. AB - Endothelin-1 (ET-1) is a potent vasoactive peptide which generally exerts its effect on target cells by increasing [Ca++]i. Both vasoconstriction (resulting in an increase in perfusion pressure) and increased [Ca++]i are actions of ET-1 that may result in cholestasis. Single-pass isolated perfused rat liver (IPRL) were used, and [Ca++]i was measured in both populations of hepatocytes and single cells. ET-1 (0.1-100 nM) induced a dose-dependent increase in perfusion pressure and decrease in bile flow. Perfusion pressure increased by 112% (p < 0.001) and bile flow decreased by 17% (p < 0.008) in response to 2 nM ET-1. At this concentration of ET-1, but not at higher concentrations, the cholestasis was abolished (p > 0.18 vs basal) and the rise in perfusion pressure was decreased (by 62%; p < 0.002) by the vasodilator papaverine. This ET-1 concentration also had no measurable effect on [Ca++]i in isolated hepatocytes. Taken together these findings indicate that ET-1 inhibits bile flow in IPRL and suggests that this effect is mediated by vasoconstriction and not by changes in hepatocyte cytosolic Ca++. PMID- 8466502 TI - Overexpression of a UV-damage recognition protein in a UV-sensitive human colon cancer cell line that features multidrug-resistant phenotype. AB - We have previously hypothesized that the level of UV-damage recognition protein (UVDRP) is a potential indicator of DNA-damage-mediated sensitivity or resistance of human cells to UV radiation [Chao, C.C.-K., Biochem. J. 282, 203-207, 1992]. In this study, we detected a 2-fold increase in the UVDRP binding activity in a UV-sensitive multidrug-resistant (MDR) human colon cancer cells compared to the parental SW620 cells. However, the MDR cells did not display enhanced DNA repair. The data is consistent with the conclusion that DNA excision repair is not the sole determinant of cellular sensitivity to genotoxic agents. The results also suggest that recognition of damaged DNA may be associated with generating a signal which mediates cellular sensitivity to UV radiation. PMID- 8466503 TI - Autocrine/paracrine function of parathyroid hormone-related peptide in rat osteoblast-like cells. AB - Parathyroid hormone-related peptide (PTHrP) may be synthesized in or near its target tissues and acts by autocrine and/or paracrine fashions. The rat clonal strain of the osteoblast-like cell, ROS 17/2.8-5, can express low levels of PTHrP in the cytoplasm; however, the autocrine function of PTHrP in ROS cells has not yet been clarified. We created PTHrP expression vectors and transfected them into cells in order to elucidate the functional role of PTHrP on their own target cells. Sense and antisense rat PTHrP expression vectors (pSV2 neo-ECE-rPLP) were transfected into ROS cells independently and cultured for 72 hours. Cells overexpressing PTHrP were detected by immunocytochemical analysis and confirmed by Northern blot analysis, respectively. These transfected cells demonstrated mitogenic activity as determined by BrdU uptake staining. These findings suggest the functional role of PTHrP on their own PTHrP expressing cells via an autocrine/paracrine fashion. These PTHrP-overexpressing ROS cells provide a model in vitro system to clarify the mechanism by which PTHrP acts in an autocrine/paracrine fashion. PMID- 8466504 TI - Identification and partial characterization of phospholipase D in the human amniotic membrane. AB - The enzymatic activity of phospholipase D and its characteristics have been examined in human amnion tissue. The phospholipase D activity was not Ca(2+)- or Mg(2+)-dependent and was activated by unsaturated fatty acids. The optimal pH of phospholipase D was 5.5. The phospholipase D activity in amnion tissue was highest in the microsomal fraction, and preferentially utilized phosphatidylcholine as a substrate. The phospholipase D activity of the microsomal fraction of amnion tissue obtained at term before labor onset (34.0 +/ 16.3 nmol/hour/mg protein, mean +/- SD, n = 11) was significantly (p < 0.05) higher than the activity in this tissue obtained from women in the mid-trimester (15.0 +/- 7.5 nmol/hour/mg protein, n = 9). PMID- 8466505 TI - Permanent gases inside healthy and microbially infected cotton fruit during development. AB - Permanent gases inside developing cotton fruit (Gossypium hirsutum L.) were, by weight, 46% nitrogen, 29% oxygen, 4% argon and 20% carbon dioxide, whereas plant canopy air assayed at 73% nitrogen, 25% oxygen, 2% argon and 0.3% carbon dioxide. Light exposure, fruit age, and mild infection (Erwinia) had no compositional effect but aggressive infection (Aspergillus) raised carbon dioxide content to 31% by weight and correspondingly lowered oxygen to 17%. Respiration with oxygen replenishment except during aggressive infection accounted for the fruit gas compositions. PMID- 8466506 TI - Lipopolysaccharide-induced expression of prostaglandin H synthase-2 in alveolar macrophages is inhibited by dexamethasone but not by aspirin. AB - Alveolar macrophages cultured with lipopolysaccharide release markedly increased amounts of prostanoids upon subsequent stimulation, an effect that is due to induction of prostaglandin H synthase-2 (J. Biol. Chem., (1992), 267, 14545 14550, and Biochem. Biophys. Res. Comm., (1992), 187, 1123-1127). The effects of dexamethasone and aspirin on this enhanced formation of thromboxane by stimulated lipopolysaccharide-primed alveolar macrophages were investigated. Under conditions of maximum inhibition, dexamethasone and aspirin decreased the formation of thromboxane by approximately 50% and 80%, respectively. Expression of lipopolysaccharide-induced prostaglandin H synthase-2 in dexamethasone-treated macrophages was similarly inhibited by about 50%, as determined by Northern blot and immunoprecipitation. In contrast, levels of lipopolysaccharide-induced prostaglandin H synthase-2 mRNA and protein were not reduced in aspirin-treated macrophages. We conclude that inhibition of prostaglandin H synthase-2 expression represents a mechanism by which dexamethasone, but not aspirin, may inhibit prostanoid formation by alveolar macrophages. PMID- 8466507 TI - Differentiation and apoptosis of murine neuroblastoma cells N1E115. AB - The mode and the kinetics of differentiation and death of murine N1E115 neuroblastoma cells induced by dimethyl sulfoxide and other nonspecific factors in vitro were investigated. After morphological differentiation neuroblastoma cells die by apoptosis which is indicated by characteristic morphological features and by internucleosomal DNA fragmentation. Durations of both differentiation and apoptosis are dependent on the nature of stimuli used. Protein synthesis inhibitor cycloheximide does not prevent differentiation and apoptosis of neuroblastoma cells induced by dimethyl sulfoxide and even accelerates both processes. The relationship between cell death and differentiation is discussed. PMID- 8466508 TI - Epidermal growth factor binding and stimulation of inositol trisphosphate production in basolateral membranes from dog kidney. AB - To ascertain whether epidermal growth factor (EGF) receptors are present in proximal tubular basolateral membranes from dog kidney and whether the growth factor activates phospholipase C at this site, we measured binding of 125I-EGF in isolated membranes and determined whether incubation of the membranes with EGF results in generation of inositol trisphosphate. Specific binding of 125I-EGF to basolateral membranes was observed that was half-maximally inhibited by approximately 7 x 10(-10) M EGF. The specific binding capacity of basolateral membranes for EGF averaged 45.9 fmol/mg protein. 125I-EGF was crosslinked to 2 proteins in basolateral membranes with M(r)s of 170,000 and 150,000. EGF stimulated phosphorylation of a 170,000 M(r) protein. Incubation of basolateral membranes with EGF stimulated inositol trisphosphate production in a concentration-dependent manner. We conclude that EGF activates a phospholipase C activity that cleaves phosphatidylinositol 4,5-bisphosphate within the basolateral membrane. PMID- 8466510 TI - Enzymatic basis for altered ascorbic acid and dehydroascorbic acid levels in diabetes. AB - Abnormal plasma ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels observed in diabetes may be correlated to a deficiency in the recycling of AA. Ascorbic acid and DHAA levels are altered in diabetic liver in the present study. In addition, a coupling of the hexose monophosphate (HMP) shunt by way of NADPH to glutathione reductase and subsequent DHAA reduction is demonstrated. Ascorbic acid production was assayed directly and by way of the HMPS pathway. Results indicate that AA production from DHAA via the HMPS pathway occurs, and is significantly decreased in diabetic liver. Glucose-6-phosphate dehydrogenase (G6PDH) activity is shown to be decreased in diabetic liver. Since G6PDH is essential in providing NADPH for the reduction of glutathione required for subsequent DHAA reduction, its decreased activity is consistent with altered levels of AA and DHAA observed in diabetic tissues. PMID- 8466509 TI - Molecular cloning of human epimorphin: identification of isoforms and their unique properties. AB - Epithelial-mesenchymal interactions are crucial for various epithelial tissue organizations and epimorphin is one of the important signaling molecules from the mesenchyme. The sequence analysis of a human homologue revealed that both of primary and predicted secondary structures of epimorphin are highly conserved among species and this molecule has some isoforms including a putative soluble type. I found that human epimorphins also have a large discrepancy in molecular masses as the case of mouse (around 33kD are predicted by the sequences whereas two protein bands of 60-70kD and 150kD are detected in the cells), and it can be explained, at least in part, by the SDS-resistant complexes formed in the microsomal membranes. PMID- 8466511 TI - Cleavage arrest in Xenopus embryos injected with a human c-myc gene. AB - The c-myc protein has been implicated in cell proliferation and differentiation of various cell lines, but its function in early embryos of Xenopus is obscure. We introduced the c-myc gene into embryos using a pcDL-SR alpha plasmid with an efficient promoter of the gene. It was found that fertilized eggs injected with the c-myc gene were arrested at the 4-cell stage within 1 h of the injection, when the plasmid that carried c-myc gene but not the plasmid that carried defective c-myc gene was injected. These results also suggest that Xenopus embryos already have the ability to transcribe an exogenously injected c-myc gene at the 4-cell stage. PMID- 8466512 TI - A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase. AB - Palmitoyl-CoA dehydrogenase activity in skin fibroblasts from seven patients with unidentified defects of fatty acid oxidation was measured in the presence and absence of antibodies against medium-chain, long-chain, and very-long-chain acyl CoA dehydrogenases (VLCAD). Two of the patients, 4-5 month old boys, were found to have a novel disease, VLCAD deficiency, as judged from the results of very low palmitoyl-CoA dehydrogenase activity and the lack of immunoreactivity toward antibody raised to purified VLCAD. PMID- 8466513 TI - Two insulin genes are present in the salmon genome. AB - According to the accepted hypothesis, polyploid evolution is necessary to achieve meaningful gene duplication. Some fish, namely those belonging to the suborder Salmonidae, appear to be autotetraploid species that probably originated from a diploid ancestor relatively recently and that appear to be progressing toward diploidization to various degrees. The Pacific chum salmon (Oncorhynchus keta) has almost completed this process of diploidization. Thus, with regard to practically any gene product, theory predicts a freshly diploidized, autotetraploid species to possess twice the number of gene loci as diploid animals. Here we show that the chum salmon genome contains two nonallelic insulin genes that are both expressed in chum salmon Brockman bodies. Nucleotide sequence analysis reveals structural diversification of this pair of duplicated genes. PMID- 8466514 TI - Alboaggregin-B and botrocetin, two snake venom proteins with highly homologous amino acid sequences but totally distinct functions on von Willebrand factor binding to platelets. AB - Alboaggregin-B (AL-B) (Peng et al., Biochemistry (1991) 30, 11529-11536) was highly purified from the snake venom of Trimeresurus albolabris and characterized structurally and functionally, comparing with botrocetin, another snake venom protein recently characterized (Usami et al., Proc. Natl. Acad. Sci. USA (1993) 90, 928-932). Both the venom proteins are a heterodimer and show a high degree of sequence homology to each other and also to C-type lectins. Botrocetin specifically binds to von Willebrand factor (vWF), whereas AL-B binds to platelet glycoprotein (GP) Ib without affecting the binding of botrocetin to vWF. The binding of AL-B to GPIb does not potentiate the platelet aggregation even by exogenous fibrinogen, suggesting that AL-B binding to GPIb does not activate GPIIb/IIIa complex. PMID- 8466515 TI - Voltage-dependent potassium currents in cultured human retinal pigment epithelial cells. AB - Membrane currents in primary cultures of human retinal pigment epithelial cells were studied using the whole-cell configuration of the patch-clamp technique. Two types of voltage-dependent whole-cell currents were observed. First, a time- and voltage-dependent outward current, which was activated by depolarizing the cell to potentials more positive than -30mV, was sensitive to Ba2+ (10mM), 4 aminopyridine (10mM) and TEA+ (30mM). Tail-current analysis indicated that the current was mainly carried by K(+)-ions. Second, hyperpolarization of the cell to potentials more negative than -70mV led to a time- and voltage-dependent inward current which was blocked by Ba2+ (10mM) and 4-aminopyridine (10mM), but not by TEA+ (30mM). In summary, human retinal pigment epithelial cells in primary culture express currents which indicate the presence of a delayed rectifier K(+) channel and an inward rectifier K(+)-channel. PMID- 8466516 TI - Theoretical analysis of amino acid sequence of human dystrophin. AB - Human muscular dystrophy, the fatal disease, is caused by the genetic abnormality of dystrophin. The question whether dystrophin is an intrinsic membrane protein or not was investigated by calculating the average value and the long periodicity of hydrophobicity of amino acid sequence. The periodicity was estimated by a maximum entropy method of Fourier transformation. The results indicated that a fragment from 3101-st to 3200-th residues of dystrophin contains several transmembrane helices. The hydropathy plot of this region strongly suggests four transmembrane helices, indicating that both ends, N-and C-termini, are located in the cytoplasmic sides with firm anchoring into membrane by these helices. PMID- 8466517 TI - Evidence for the involvement of G proteins in the modulation of 22Na and 45Ca fluxes in myogenic L6 and aortic smooth muscle cells. AB - Preincubation of rat skeletal muscle derived L6 myoblasts with 10 mM NaF increased, the activity of Na+/H+ exchanger, and the uptake of 45Ca by 2 and 5 folds, respectively. In cultured vascular smooth muscle cells (CVSMC) of rat aorta, NaF increased the activity of Na+,K(+)-pump, Na+/H+ exchanger, passive permeability for Na+, and 45Ca uptake by 1.6, 9, 2, and 9 folds, respectively. Both, in CVSMC and L6 cells, the effect of NaF on the Na+/H+ exchanger and 45Ca uptake were significantly augmented by 20 microM AlCl3. No effect of AlCl3 on the NaF dependent changes in ion flux was seen in rat erythrocytes. The results suggest that in L6 and CVSMC cells, the Na+/H+ exchanger and Ca++ uptake pathway(s) are activated by GTP-binding proteins. PMID- 8466518 TI - The structure and characteristics of a fourth allele of polymorphic N acetyltransferase gene found in the Japanese population. AB - Polymorphic N-acetyltransferase (NAT2), which exists in the human liver and metabolizes a wide spectrum of arylamine, is encoded by one gene (NAT2). We have identified the mutations of a fourth NAT2 allele (allele 4) which we previously found in the Japanese population. Compared with allele 1, which expresses a high enzyme activity, allele 4 has 3 nucleotide differences. 2 are missense mutations at nucleotide position (nt) 341 and 803. The other is a silent mutation at the KpnI site. From the result of expression studies of chimeric gene constructs between allele 1 and allele 4 in Chinese hamster ovary cells, nt 341 missense mutation of the allele 4 which causes the Ile-114 to Thr change is responsible for the low enzyme activity of NAT2 protein. PMID- 8466519 TI - Endothelin-1 induces contraction of bile canaliculi in isolated rat hepatocytes. AB - To examine the effects of endothelin-1(ET-1) on bile canalicular contractions, rat hepatocytes were isolated by a collagenase perfusion technique and cultured on p-n-p-vinylbenzenyl-D-lactonamide-coated dishes under serum-free conditions. The frequency of bile canalicular contractions was expressed by the percentage of the number of bile canaliculi(BC) that contracted compared to the total number of BC observed for 10 min. The treatment of the hepatocytes with ET-1 increased the frequency of contraction of the BC in a dose-dependent manner up to 2nM, control: 10.4%; 0.5nM ET-1:31.6%; 1nM ET-1:54.0%; 2nM ET-1:58.0%; 4nM ET-1:58.9%. The contraction, once it occurred, lasted for rest of the observation period. We also observed a transient increase in the concentration of intracellular Ca in cultured hepatocytes upon the addition of ET-1 to the medium. These results suggest that ET-1 plays an important role in the mortility of BC in vivo. PMID- 8466520 TI - Endothelin-1 is produced and secreted by neonatal rat cardiac myocytes in vitro. AB - Production of endothelin-1 in the cultured neonatal rat cardiac myocytes was investigated. Studies on the cultured cardiac myocytes with reverse transcription polymerase chain reaction followed by Southern hybridization indicated that mRNA of ET-1(preproET-1 mRNA) was expressed by cardiac myocytes. ET-1 polypeptide was also detected in the cultured cardiac myocytes. Moreover, ET-1 was secreted into the culture medium by them. These results suggest that the cardiac myocytes, which have been regarded as target cells of ET-1, are able to synthesize and secrete ET-1. Furthermore, there may be a possible autocrine mechanism of ET-1 in the myocytes of a heart. PMID- 8466521 TI - Molecular cloning and characterization of the promoter region of the human c-erbA alpha gene. AB - The c-erbA alpha gene encodes the alpha type thyroid hormone receptor. This gene is expressed in various types of cells, its expression being relatively high in the central nervous system. A genomic clone that contains the 5'-terminal portion of the human c-erbA alpha gene was isolated. The 615 base pair (bp) 5'-flanking sequence of the c-erbA alpha gene showed promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into HeLa cells. Nine transcriptional initiation sites were detected within this sequence by S1 nuclease protection analysis. DNA sequence analysis showed that the promoter region contains ten putative binding sites for transcriptional factor Sp1 in the GC rich region (86%). Three putative cAMP responsive elements (CRE) and one putative TPA responsive element (TRE) were identified upstream of the GC rich region. The c-erbA alpha promoter sequence also contains a putative binding site for the Krox-20 transcriptional factor, which is thought to play a role in early development of the mouse central nervous system. PMID- 8466522 TI - Endothelin 1 mediates endothelial cell-dependent proliferation of vascular pericytes. AB - The influence of endothelial cells on the growth of vascular pericytes was investigated using human umbilical endothelial cell and bovine retinal pericyte co-culture systems. When pericytes were cultured with endothelial cells, the number of viable pericytes increased significantly, regardless of the presence or absence of physical contact between the two cell types, indicating that endothelial cells can induce proliferation of pericytes through certain secreted factor(s). Evidence that endothelin 1 mediates this action was obtained: endothelin 1 added to the medium was able to substitute for the feeder layer of endothelial cells, and an antiserum against endothelin 1 could neutralize the ability of endothelial cells to promote pericyte growth. RNA blot analysis revealed that pericytes express mRNA for type-A endothelin receptor, a high affinity receptor of endothelin 1. PMID- 8466523 TI - Nitric oxide stimulates the ADP-ribosylation of actin in human neutrophils. AB - ADP-ribosylation is an important post-translational protein modification; however, endogenous substrates are poorly characterized. In these studies we examined the effects of nitric oxide on the ADP-ribosylation of neutrophil proteins. Purified cytosol and plasma membrane were incubated with 32P-NAD (5 microM, 1 microCi, 30 min) in the presence or absence of nitric oxide. Nitric oxide induced the ADP-ribosylation of the 37 kD substrate present only in cytosol. Nitric oxide treatment of plasma membrane plus cytosol revealed the ADP ribosylation of an additional 43 kD protein. This 43 kD substrate was identified as actin by both phalloidin precipitation and immunoblot (2-D) gel using specific anti-actin antibodies. The data indicate that nitric oxide stimulates the ADP ribosylation of two discrete substrates in fractionated PMN, one of which can be identified as actin. NO-induced ADP-ribosylation may contribute to the modulatory effect of nitric oxide on neutrophil functions, including F-actin assembly. PMID- 8466524 TI - Solution structure of casokefamide. AB - Casokefamide (Tyr-D-Ala-Phe-D-Ala-Tyr-NH2) is a synthetic peptide derived from the beta-casomorphin sequence, designed to increase the resistance to gastric proteases. Casokefamide binds to both mu and delta-opioid receptors, while beta casomorphins and its fragments are typical mu-opioid receptor agonists. Furthermore, casokefamide can affect gastric acid and pancreatic exocrine secretions and also gastrointestinal motility. We have undertaken a conformational study on this peptide based on NMR measurements in a DMSOd6/H2O cryomixture at 265 K and energy calculations. The predominant conformation is characterised by the absence of regular structures and intramolecular hydrogen bonds. The conformation of the message domain is reminiscent of the shape of several peptidic and non peptidic opiates, with the D-Ala2CH3 group sandwiched between Tyr1 and Phe3 aromatic rings. PMID- 8466525 TI - Cloning of the rat cyclin-dependent kinase 4 cDNA: implication in proliferation dependent expression in rat tissues. AB - To identify protein kinases that may regulate fetal growth and differentiation, we used an oligonucleotide probe encoding the conserved sequence of serine/threonine kinases to screen a fetal lung cDNA library. Several clones were isolated and sequenced, one of which encodes the rat homolog of the 34 kilodalton cyclin-dependent kinase 4 (p34cdk4). Northern blot analyses of pre- and postnatal rat tissues show that rat cdk4 is expressed in a developmentally regulated pattern in all tissues examined. The mRNA is also significantly decreased in cells that are arrested in the G1 phase of cell cycle. The regulated expression of rat cdk4 is consistent with a proliferation-, rather than a differentiation-, dependent pattern. PMID- 8466526 TI - 1H-detected in vivo 13C NMR spectroscopy and imaging at 2T magnetic field: efficient monitoring of 13C-labeled metabolites in the rat brain derived from 1 13C-glucose. AB - Gradient-select hetero-nuclear multiple quantum coherence in nuclear magnetic resonance (NMR) an indirect method of detecting nuclei in low sensitivity by 1H NMR, was used to observe 13C-enriched metabolites in the rat brain in vivo, with a 2 T NMR system. We detected the accumulation of 13C-labeled glucose and its metabolites, glutamine and/or glutamate, in less than 5 min. The extension of this technique to chemical shift imaging permitted the localization of these chemicals in the rat brain. This approach may have various applications for non invasive monitoring of 13C-labeled compounds in humans and other animals. PMID- 8466527 TI - Geranylgeranylacetone used as an antiulcer agent is a potent inducer of differentiation of various human myeloid leukemia cell lines. AB - Low concentrations of geranylgeranylacetone (GGA), known as an antiulcer agent (Teprenone), induces differentiation of various human myeloid leukemia cell lines. The cell lines examined in the present study were myeloblastic ML1, histiocytic U937, promyelocytic HL60, and multipotential K562. All of these cell lines were induced to differentiate by 20 microM GGA, as measured by NBT staining. Neither polyprenylacetones, with more or fewer isoprene units than the geranylgeranyl group, nor polyprenylalcohols had no differentiation-inducing activity. GGA used in combination with RA or TNF-alpha increased ML1 cell differentiation. The present results suggest that GGA may be a useful agent in differentiation therapy of leukemia. PMID- 8466528 TI - The mouse low density lipoprotein receptor gene: cDNA sequence and exon-intron structure. AB - The low density lipoprotein (LDL) receptor plays a central role in the cholesterol metabolism. The cDNA sequence of the mouse low density lipoprotein receptor (Ldlr) gene has been determined and shows 76% homology with the human gene. The exon-intron structure has been determined for the 129/J mouse strain. The gene is composed of 18 exons and spans a region of 28 kb. In addition, the promoter regions of the mouse and human genes are homologous. Northern blot analysis revealed an mRNA of approximately 5 kb. The cloning of the Ldlr gene will enhance the usefulness of the mouse for the study of cholesterol metabolism and, in particular, for carrying out gene targeting experiments. PMID- 8466529 TI - Molecular cloning and sequencing of zeta-crystallin/quinone reductase cDNA from human liver. AB - Zeta-crystallin is an enzyme-crystallin highly expressed in the lens of some hystricomorph rodents and camels. It has been shown to have a novel NADPH: quinone oxidoreductase activity and is present at enzymatic levels in a variety of tissues from various mammals. We report here the cDNA cloning of zeta crystallin from a human liver library. One clone with the complete open reading frame was obtained. Ten nucleotides of the 5' and 796 of the 3' nontranslated regions are present in the clone including two possible polyadenylation signals. The deduced amino acid sequence is 328 residues long with a calculated molecular mass of 34910 daltons and isoelectric point of 8.73. It shows 84% identity with the guinea pig protein. PMID- 8466530 TI - Effect of retinoic acid on osteocalcin gene expression in human osteoblasts. AB - It is well known that the expression of osteocalcin, the only recognized osteoblast-specific protein, is regulated by 1 alpha-25-dihydroxyvitamin D3 through a distinct vitamin D3 receptor and a cis-acting DNA response element. In addition, recent data obtained with plasmid constructs have shown a positive interaction between retinoic acid activated receptor(s) and the osteocalcin gene promoter. Our studies, carried out on primary cultures of human osteoblasts, have demonstrated for the first time the activation of the osteocalcin gene expression by retinoic acid. Moreover, a remarkable synergistic effect between the hormonal forms of vitamin A and D3 on the synthesis of this bone-specific protein was observed. PMID- 8466531 TI - Bcl-2 gene is highly expressed during neurogenesis in the central nervous system. AB - An analytical method for quantitation of the RNA transcripts of murine bcl-2 gene was developed. The PCR products from bcl-2 alpha and bcl-2 beta mRNA were fluorometrically analyzed and their specific contents were calculated by the internal standard method. Both bcl-2 mRNAs in adult mice were transcribed at the highest level in the thymus and at a comparable level in the spleen. Aside from the immune system, the brain gave the most abundant levels of the bcl-2 mRNAs. The ratios of bcl-2 beta mRNA to bcl-2 alpha mRNA in the thymus and spleen were significantly higher than those in other tissues. During development of the brain, the bcl-2 alpha and bcl-2 beta mRNA levels were highest on embryonic day 15, and about two and three times higher than those of adult, respectively. The results suggest that the bcl-2 gene functions to regulate development and survival of neurons in the central nervous system. PMID- 8466532 TI - Specific interaction of guanidine hydrochloride with essential carboxyl group of xylanase from alkalothermophilic Bacillus sp. AB - Experimental evidence for the specific interaction of guanidine hydrochloride with the carboxyl group of xylanase has been presented for the first time. Guanidine hydrochloride (0.1 M) inactivated the xylanase from alkalothermophilic Bacillus sp. to 50% without affecting the conformation of the protein as determined by the fluorometric profile. The kinetic analysis indicated a competitive type of inhibition and a requirement of 1.4 molecules of guanidine hydrochloride per molecule of the enzyme for inhibition. Maximum inhibition occurred at the pH which is optimum for the enzyme activity. The reaction of guanidine hydrochloride with the enzyme prior to modification by Woodward's Reagent K, a specific inhibitor of the carboxyl group, made it inaccessible for modification as indicated by absorbance data at 340 nm. Urea, sodium dodecyl sulphate, LiCl, KCl and NaCl at 0.1 M concentration each had negligible effect on the enzyme activity. PMID- 8466533 TI - Satellite cell myogenesis is highly stimulated by the kinase inhibitor iso-H7: comparison with HA1004 and staurosporine effects. AB - Differentiation of rat satellite cells, measured by cell fusion into myotubes and isozymic conversion of creatine kinase and phosphoglycerate mutase, was shown to be highly increased in the presence of 1-(5-isoquinolinylsulfonyl)-3 methylpiperazine (iso-H7). This substance inhibited both protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) activities with similar IC50 between 22 and 34 microM. Iso-H7, as well as the PKA inhibitor HA1004 increased myogenic differentiation without altering the proliferation of satellite cells, whereas the proliferation and the differentiation of these cells were inhibited by the PKC inhibitor staurosporine. Our results suggest a predominant negative control of PKA on satellite cell myogenesis. PMID- 8466534 TI - Enhancement of perforin by retinoic acid is mediated by protein kinase C. AB - We previously demonstrated that interleukin-2 induced murine lymphokine-activated killer cell activity is augmented by retinoic acid. The enhanced cytotoxicity is significantly correlated with the increase in PKC. In the present study, we have shown that retinoic acid increases the expression of perforin, a potent cytolytic mediator, at both protein and mRNA levels. This enhancement can be induced by a direct stimulation of PKC signaling pathway, as manipulated by a short term incubation of lymphokine-activated killer cells with 12-O-tetradecanoyl-phorbol 13-acetate and ionomycin, and suppressed by PKC inhibitors. These results suggest that PKC plays a regulatory role in the enhancement of the expression of cytolytic mediators in retinoic acid-augmented lymphokine-activated killer cells. PMID- 8466535 TI - A new method to determine the level of coenzyme Q10 in one drop of human blood for biomedical research. AB - This method has been designed to determine the levels of CoQ10 in human blood which utilizes only one drop of blood (0.05 ml). This method encourages and facilitates more frequent monitoring of blood levels of CoQ10, and of clinical importance, reveals the presence or absence of compliance. CoQ11 was used as an internal standard. The mean recovery of CoQ10 was 96%. The correlation coefficient between using 1.0 ml and 0.1 ml of blood and between using 1.0 and 0.05 ml was 0.997 in the two comparisons. Therefore, it can be accurate to monitor the level of CoQ10 in a -"finger-prick"-drop of blood, and at least 24 such determinations can be conducted in a 2-day period. PMID- 8466536 TI - Adrenoleukodystrophy: overlapping deletions point to a gene location in Xq28. AB - Adrenoleukodystrophy is a lethal X-linked neurodegenerative disorder which maps close to the red/green color pigment gene cluster in Xq28. We have reported a broad spectrum of color pigment gene changes in adrenoleukodystrophy patients, indicating that the genes may be quite close together. We now have used anonymous DNA probes centromeric to the color pigment gene cluster to analyze patients from 59 adrenoleukodystrophy kindreds. All patients showed normal hybridization using probe Fr9, 30 kb centromeric to the color pigment genes. However, using probe Fr11, 100 kb further centromeric, we found overlapping deletions in 2 patients. We isolated conventional and cosmid genomic clones encompassing 24 kb surrounding Fr11; the clones and map derived from this region localize the telomeric ends of the two deletions to distinct positions 8 kb apart. These overlapping deletions implicate this specific region as a likely site for the ALD gene. PMID- 8466537 TI - Molecular cloning of a cDNA encoding the precursor of adenoregulin from frog skin. Relationships with the vertebrate defensive peptides, dermaseptins. AB - Adenoregulin has recently been isolated from Phyllomedusa skin as a 33 amino acid residues peptide which enhanced binding of agonists to the A1 adenosine receptor. In order to study the structure of the precursor of adenoregulin we constructed a cDNA library from mRNAs extracted from the skin of Phyllomedusa bicolor. We detected the complete nucleotide sequence of a cDNA encoding the adenoregulin biosynthetic precursor. The deduced sequence of the precursor is 81 amino acids long, exhibits a putative signal sequence at the NH2 terminus and contains a single copy of the biologically active peptide at the COOH terminus. Structural and conformational homologies that are observed between adenoregulin and the dermaseptins, antimicrobial peptides exhibiting strong membranolytic activities against various pathogenic agents, suggest that adenoregulin is an additional member of the growing family of cytotropic antimicrobial peptides that allow vertebrate animals to defend themselves against microorganisms. As such, the adenosine receptor regulating activity of adenoregulin could be due to its ability to interact with and disrupt membranes lipid bilayers. PMID- 8466538 TI - Prenatal developmental expression of rat brain 5-HT1A receptor gene followed by PCR. AB - Expression of the gene encoding the serotonin 5-HT1A receptor was investigated in the brain of rats from embryonic day (ED) 10 to postnatal day 18 using PCR. The 5 HT1A receptor transcripts were first detected as early as ED 12. Their concentration increased to a maximum at ED 15 and decreased progressively to very low levels just before birth (ED 20). In 18-day-old rats, the brain stem levels of 5-HT1A receptor mRNA were higher than at ED 20 but still markedly lower than at ED 15. The high rate of expression of the 5-HT1A receptor gene for a limited period during the fetal life further supports that this receptor might be involved in the trophic action of serotonin during brain maturation. PMID- 8466539 TI - Kinetic assay for HIV proteinase subunit dissociation. AB - The kinetics and thermodynamics of the monomer--dimer equilibrium for HIV-1 proteinase are investigated in a concentration jump experiment, at a concentration of the substrate that is substantially lower than the Michaelis constant. Under these conditions the substrate-induced stabilization of the active dimer is suppressed, and the integral rate equation can be obtained in a closed form. Both the monomer--dimer bimolecular association rate constant and the corresponding equilibrium dissociation constant are obtained directly by nonlinear regression analysis of the reaction time-course. In buffers of low ionic strength and in the absence of external ligands (substrates and inhibitors), the equilibrium dissociation constant at 37 degrees C is 440 +/- 52 nM, a value significantly higher than previous estimates obtained at a comparatively high concentration of substrates. PMID- 8466540 TI - Specific binding and uptake of extracellular nicotinamide in human leukemic K-562 cells. AB - Extracellular nicotinamide is well recognized as the primary precursor to the cellular synthesis of NAD. NAD is a pivotal molecule in regulating the energy and redox potentials of cells via synthesis of ATP and NAD(P)/NAD(P)H ratios. NAD turnover in cells is very rapid due to NAD catabolism via ADP-ribosylation reactions. These facts suggest that the cellular uptake and transport of nicotinamide may not be a passive process but a highly regulated cellular event. We have utilized radiometric procedures to characterize the uptake of [14C]nicotinamide in human leukemic K-562 cells. At physiologically relevant doses of nicotinamide (< 100 microM), the uptake was saturable with a Km of 2.3 +/- 1.0 microM and a Vmax of about 1.5 +/- 0.5 pmol/10(6) cells/min. Kinetic studies revealed that nicotinamide was first taken up intracellularly and then immediately converted to NAD and 1-methyl nicotinamide. All of the nicotinamide taken up into the cell was bound tightly to plasma membranes (25,000 g pellet) with Kd values between 3.2 and 12.7 microM and a Bmax of 1.56 pmol/10(6) cells. The specificity of nicotinamide binding was demonstrated by competitive inhibition experiments using NAD analogs, nicotinamide derivatives, and agonists or antagonists of plasma membrane receptors. We conclude that there is specific binding of nicotinamide, followed by intracellular uptake and immediate synthesis to NAD. PMID- 8466541 TI - Fluvoxamine is a potent inhibitor of cytochrome P4501A2. AB - Fluvoxamine is a new antidepressant and selectively inhibits serotonin reuptake (SSRI). The present study demonstrates that fluvoxamine is a very potent inhibitor of the high-affinity O-deethylation of phenacetin, which is catalysed by cytochrome P4501A2 (CYP1A2), in microsomes from three human livers. Thus, the apparent inhibitor constant of fluvoxamine, Ki, ranged from 0.12 to 0.24 microM. Seven other SSRIs, citalopram, N-desmethylcitalopram, fluoxetine, norfluoxetine, paroxetine, sertraline and litoxetin either did not inhibit or were weak inhibitors of the O-deethylation of phenacetin. Our findings explain the mechanism of the pharmacokinetic interactions between fluvoxamine and drugs that are metabolized by CYP1A2, e.g. theophylline and imipramine. PMID- 8466542 TI - Hepatic and intrahepatic targeting of an anti-inflammatory agent with human serum albumin and neoglycoproteins as carrier molecules. AB - The anti-inflammatory agent naproxen (Nap) was covalently coupled to human serum albumin (HSA) and to the neoglycoproteins, galactose and mannose terminated HSA, to deliver this drug selectively to different cell types of the liver. Disposition of Nap20-HSA was studied in rats and compared to that of equivalent doses of mixtures of uncoupled drug and protein. The liver to kidney ratios of the drug (L/K-Nap) and the protein (L/K-prot.) were increased, indicating an improved delivery of both protein and drug to the target site. After injection of 10 micrograms Nap20-HSA the L/K-prot. was increased 15.0 +/- 0.21-fold as measured 1 hr after injection. Even after injection of 5 mg of the conjugate, the L/K-prot. was enhanced 5.6 +/- 0.34-fold and the L/K-Nap 4.6 +/- 0.23-fold as measured 1 hr after injection. Immunohistochemical staining of liver slices revealed that the endothelial cells were the main sites for hepatic uptake. Further pharmacokinetic studies of Nap20-HSA in isolated perfused rat livers showed a saturable uptake process (Vmax = 2.46 micrograms/min/10.0 g liver and Km = 4.27 x 10(-6) M). The uptake in the liver could be inhibited by various polyanionic probes, indicating the major involvement of a scavenger receptor system in the internalization mechanism of Nap20-HSA. This endothelial uptake via the scavenger receptor system is likely to be related to the increased negative charge of the Nap-albumin conjugate as was revealed by anion exchange chromatography. Studies in the intact organ and in purified liver lysosomal lysates indicate that after internalization of Nap20-HSA the conjugate is proteolytically degraded leading to the formation of the lysine conjugate of Nap. This amino acid conjugate of Nap was shown in a previous study by us to be equipotent to Nap itself with regard to prostaglandin-E2 synthesis inhibition. A pronounced altered intrahepatic distribution was observed when Nap was coupled to lactosaminated and mannosylated HSA (Lact-HSA and Man-HSA, respectively). Coupling of Nap to Lact27-HSA and Man10-HSA resulted in a major shift in intrahepatic distribution from endothelial cells to the hepatocytes and Kupffer cells, respectively. We conclude that conjugation of Nap to HSA itself results in a selective delivery to endothelial cells and that the local proteolysis of the conjugate produces an active catabolite. Selective delivery to other cell types of the liver can be achieved by attaching naproxen to neoglycoproteins with an appropriate type and number of sugar groups. PMID- 8466543 TI - Inhibition of glutathione S-transferases from rat liver by basic triphenylmethane dyes. AB - (1) Basic triphenylmethane dyes related to pararosanilin inhibit class alpha glutathione S-transferases (GSTs) from rat liver. The inhibitory potency of each dye correlates with its octanol-water partition coefficient. Values of Ki determined at pH 6.5 ranged from about 1 x 10(-7) M for Ethyl violet to 7 x 10( 5) M for Methyl green. GST 3-3, a class mu isoenzyme, was an order of magnitude less sensitive to inhibition by Ethyl violet. (2) All of the dyes tested were bleached to varying degrees by glutathione. The bleaching appears to result from the formation of an adduct between the dye and glutathione. At pH 6.5, adduct formation is significant only for Malachite green and Methyl green. There is kinetic evidence that for these dyes the adduct contributes significantly to the overall inhibition. It is probable that at physiological pH, all of the dyes would exist to a significant extent in the adduct form. (3) The dyes are excreted extensively in the bile, at least partly as the glutathione adduct. The free dye is regenerated on standing, it is assumed as a result of removal of glutathione by oxidation. PMID- 8466544 TI - Effect of malaria infection and endotoxin-induced fever on phenacetin O deethylation by rat liver microsomes. AB - We have investigated the effect of malaria infection with the rodent parasite Plasmodium berghei and fever induced by Escherichia coli endotoxin on the metabolism of phenacetin to paracetamol by rat liver microsomes from young (4 weeks old) male Wistar rats (N = 5 in control and fever groups; N = 10 in malaria infected group). Following determination of % parasitaemia, the malaria-infected group was divided into a low parasitaemia subgroup (N = 5; mean % parasitaemia = 9.87 +/- 2.6) and a high parasitaemia subgroup (N = 5; mean % parasitaemia = 36.6 +/- 8.1). The control group received normal saline. Total microsomal protein was not significantly affected by fever or malaria infection while cytochrome P450 levels were reduced by approximately 50% in the high parasitaemia subgroup, 20% in the low parasitaemia subgroup and 20% in the endotoxin-treated group. Phenacetin-O-deethylation kinetics were biphasic in both control and malaria infected rats, but monophasic in endotoxin-treated rats. Total apparent intrinsic clearance (CL(int),total; calculated as Vmax/Km; Vmax is maximum velocity, Km is Michaelis constant) of phenacetin was reduced approximately 6-fold in low parasitaemia, 30-fold in high parasitaemia and 35-fold in fever. There was a poor correlation between CL(int),total and % parasitaemia (r = -0.6). However, log CL(int),total correlated inversely with % parasitaemia (r = -0.9), suggesting that Cl(int),total decreased exponentially with an increase in % parasitaemia. Phenacetin O-deethylation is a marker for cytochrome P4501A2 activity and the results of the present study suggest that both malaria infection and fever might specifically reduce P4501A2 activity in the rat. PMID- 8466545 TI - Effect of malaria infection and endotoxin-induced fever on the metabolism of antipyrine and metronidazole in the rat. AB - Antipyrine and metronidazole were administered as a cocktail to young (4 weeks old) male Wistar rats (N = 12 for each treatment) to investigate the effect of malaria infection due to the rodent parasite Plasmodium berghei and Escherichia coli endotoxin-induced fever on the metabolism of the two compounds in vivo. Control rats received normal saline. Antipyrine and metronidazole clearances were estimated from a single saliva sample while the formation clearances of their metabolites (in malaria-infected and control rats) were estimated from the product of clearance of parent drug and the fraction of the administered dose excreted as metabolites in urine in 24 hr. Rats treated with endotoxin produced no urine during this period. Malaria infection had no effect on clearance of antipyrine or on formation clearance of any of its metabolites. However, the clearance of metronidazole was reduced by approximately 20% compared with controls as a result of decreased formation of hydroxymetronidazole. Fever decreased clearance of both antipyrine and metronidazole by approximately 36% and 23%, respectively. These results demonstrate that both malaria infection and fever can influence P450-dependent drug metabolism and the effects seen appear to be isozyme-selective. PMID- 8466546 TI - Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes. AB - To study the mechanism of centrilobular damage developing in the centrilobular region after high doses of acetaminophen (APAP), its metabolism and toxicity were compared in periportal and perivenous hepatocytes isolated by digitonin/collagenase perfusion. Contrary to earlier reports, based on perfusions, no evidence for a periportal dominance of APAP sulfation could be observed. Glucuronidation, the dominant pathway of conjugation at high (5 mM) APAP concentration, was faster in perivenous cells. During primary culture, prolonged exposure (> or = 24 hr) to 5 mM APAP damaged perivenous cells, with a higher P450 2E1 level than periportal cells. When cells were isolated from ethanol-pretreated rats, to induce P450 2E1 levels specifically in the perivenous region, perivenous hepatocytes exhibited enhanced APAP vulnerability and extensive glutathione depletion. In contrast, corresponding periportal cells retained good viability. Isoniazid, an inhibitor of cytochrome P450 2E1, protected cells against APAP toxicity and prevented glutathione depletion. Induction of P450 2E1 also caused a 3-fold increase in the covalent binding of reactive intermediates from [14C]APAP, and this increase was mainly confined to perivenous cells. These results indicate that in rat liver there is only slight perivenous zonation of APAP conjugation and suggest that zone-specific APAP activation, mediated by the regional expression of ethanol-inducible cytochrome P450 2E1, is responsible for the characteristic centrilobular liver damage elicited by APAP. PMID- 8466547 TI - Role of polymorphic and monomorphic human arylamine N-acetyltransferases in determining sulfamethoxazole metabolism. AB - Sulfonamides are associated with a variety of adverse reactions, some of which have been linked with the classical acetylator phenotypes. Although the slow acetylator phenotype has been identified as a risk factor for hypersensitivity reactions to sulfamethoxazole (SMX), the disposition of this compound appears not to be affected by the acetylation polymorphism in vivo in humans. We therefore investigated the acetylation of SMX by monomorphic (NAT1) and polymorphic (NAT2) arylamine N-acetyltransferases in humans with the objective of determining their role in the metabolism of SMX. SMX was acetylated by both NAT1 and NAT2. Km values determined in hepatic cytosol for NAT1- and NAT2-mediated acetylation of SMX were 1.2 mM and approximately 5 mM, respectively, at an acetyl coenzyme A concentration of 100 microM. Mononuclear leukocytes, which contain only NAT1, had a Km value of 1.2 mM. Km values determined with recombinant NAT1 and NAT2 proteins expressed in Escherichia coli were 1.5 mM and approximately 15 mM, respectively. The higher affinity of NAT1 for SMX indicates that acetylation by this enzyme will predominate at therapeutic plasma concentrations, in agreement with the observed in vivo monomorphic acetylation of SMX. NAT1 may be the primary determinant of SMX systemic metabolic clearance. However, in the hepatocyte NAT2 variation may be an important competitive pathway which influences the extent of oxidative metabolism of SMX to its reactive hydroxylamine metabolite. Therefore, variation in both monomorphic and polymorphic N-acetyltransferases may play a role in determining susceptibility to sulfamethoxazole toxicity. PMID- 8466548 TI - Effect of valproate on lipogenesis in neonatal rat brain. AB - The effect of valproate on lipogenesis in brain slices from early neonatal rats was studied. The rate of lipid synthesis from lactate and 3-hydroxybutyrate, but not from glucose, was decreased significantly by 1 mM valproate. Separation by high performance liquid chromatography of brain lipids showed that valproate inhibited the synthesis of major phospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine) from lactate and major sterols (desmosterol, cholesterol and lanosterol) from lactate and 3-hydroxybutyrate. Valproate did not affect sterol synthesis but slightly enhanced phospholipid synthesis from glucose. However, the ratio of phosphatidylserine/phosphatidylethanolamine synthesis was decreased from lactate, glucose and 3-hydroxybutyrate, suggesting that valproate changes phospholipid composition of brain structures. These changes may contribute to the pharmacological action of the drug. PMID- 8466549 TI - Synthetic C5a receptor agonists. Pharmacology, metabolism and in vivo cardiovascular and hematologic effects. AB - Recent investigations have produced novel compounds that act on the receptor for anaphylatoxin C5a. These products are C-terminal analogues of C5a, some of which are modified extensively. We have measured the receptor affinities of such analogues in a binding assay on human neutrophils (PMNs). We have also characterized their pharmacological profiles in vitro on the isolated rabbit portal vein and pulmonary artery, on superoxide release by PMNs as well as in vivo in the anesthetized rabbit (acute hypotensive and neutropenic effects). The metabolic resistance of these analogues was also evaluated in the presence of different peptidases. One of these compounds, MePhe-Lys-Pro-D-Cha-Phe-D-Arg, behaved as an antagonist on the release of superoxide by neutrophils while exerting agonist activity in all other assays. Its partial agonist status was documented in a receptor down-regulation experiment on PMNs where its activity was compared with those of recombinant C5a and of protamine which behaves as a competitive antagonist on these cells. Degradation studies indicated that the discrepancy between the affinity of certain analogues in vitro and their potency in vivo was probably linked to their metabolic stability. PMID- 8466550 TI - Interaction of vanadate and iodate oxyanions with adenylyl cyclase of ciliary processes. AB - Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated response of FSK in the presence of VO3- was due to an increase in Vmax without a change in the apparent affinity of FSK or VO3-, and therefore differs from the potentiated response of activated G-protein (Gs) and FSK, where the affinity of FSK was increased by 1-2 orders of magnitude. Potentiation occurred at low Mg2+ and was not observed at free [Mg2+] > 3 mM. Iodate (IO3-) inhibited the FSK, ISO, and VO3 activations of AC in ciliary process membranes (IC50, 0.3 mM). In vivo topical treatment of the rabbit eye with 50 microL of 5% NaIO3 had no effect alone but completely blocked the intraocular pressure response to a 50-microL topical dose of 1% FSK and partially blocked the response to a 50-microL dose of 0.001% ISO. These findings indicate that some AC enzymes may have a binding site for oxyanions which can directly regulate enzyme activity. PMID- 8466551 TI - Effects of monoamine oxidase inhibitors on the acid metabolites of some trace amines and of dopamine in the rat striatum. AB - The effects of the administration of selective and non-selective inhibitors of monoamine oxidase (MAO) on the concentrations of three trace acid metabolites [phenylacetic acid (PAA); m-hydroxyphenylacetic acid (mHPAA); and p hydroxyphenylacetic acid (pHPAA)] and of an acid metabolite of dopamine [3,4 dihydroxyphenylacetic acid (DOPAC)] in the rat striatum were determined. Administration of brofaromine (1-100 mg/kg, s.c.) a type AMAO inhibitor, dose dependently decreased DOPAC and mHPAA levels. pHPAA levels were decreased by 100 mg/kg brofaromine, but PAA levels were unaffected. Doses of deprenyl of less than 100 mg/kg, i.p., had no effect on any of the acids, while 100 mg/kg decreased DOPAC, mHPAA and pHPAA but not PAA levels. Clorgyline, pargyline and tranylcypromine treatment decreased the levels of DOPAC, mHPAA and pHPAA but not PAA. Administration of alpha-monofluoromethyldopa, an inhibitor of aromatic amino acid decarboxylase, decreased the levels of all four acids. It was concluded that deamination of the respective parent amine by type A MAO is primarily responsible for the synthesis of DOPAC and mHPAA, but that another pathway contributes to pHPAA synthesis. It appears that either PAA arises predominantly independently from the actions of MAO or that is removal via transport or further metabolism regulates its concentration. PMID- 8466552 TI - Characterization of cannabidiol-mediated cytochrome P450 inactivation. AB - Cannibidiol (CBD) has been shown to impair hepatic drug metabolism in several animal species and to markedly inhibit mouse hepatic microsomal delta 1 tetrahydrocannabinol (THC) metabolism by inactivating specific cytochrome P450s (P450) belonging to the 2C and 3A subfamilies. Elucidation of the mechanism of CBD-mediated P450 inhibition would be clinically very important for predicting its effect on metabolism of THC and the many other clinically important drugs known to be metabolized by P450s 2C and 3A. CBD-mediated inactivation of mouse hepatic microsomal P450s did not decrease hepatic microsomal heme content. However, [14C]CBD was found covalently bound to microsomal protein in an approximately equimolar ratio to P450 loss. Immunoprecipitation of microsomal protein with antibodies raised against either P450 2C or 3A revealed that approximately equal amounts of [14C]-CBD were bound to each of these P450s after CBD-mediated inactivation. Furthermore, this specific P450 binding was equivalent to P450 loss and accounted for nearly all of the microsomal [14C]CBD irreversible binding. Although > 80% of the enzyme activities attributed to P450s 2C and 3A were inactivated by CBD at the anticonvulsant dose of 120 mg/kg, P450 2C was approximately 3-fold more sensitive than P450 3A at the lower CBD doses tested. CBD analogs were synthesized in order to elucidate the chemical pathways for CBD mediated P450 inactivation in vivo. Oxidations at allylic carbon positions or saturation of either the exocyclic double bond or both double bonds of the terpene moiety did not markedly affect the inhibitory properties of the analogs. Methylation of both phenolic groups of the resorcinol moiety completely blocked the P450-inhibitory properties of this analog, revealing the involvement of a free hydroxyl group in the inactivation process. Rotation of the resorcinol moiety in abnormal-CBD did not impair the inhibitory properties of the analog, suggesting that the position of the hydroxyl group relative to the terpene ring is unimportant. Further studies are required to fully understand the chemical basis of CBD-mediated P450 inactivation. PMID- 8466553 TI - Attenuation of myocardial reperfusion injury by reducing intracellular calcium overloading with dihydropyridines. AB - The effects of three different dihydropyridine (DHP) calcium channel antagonists, nisoldipine, nimodipine, and nifedipine, on myocardial ischemic and reperfusion injury were studied using isolated rat hearts subjected to ischemia and reperfusion. Hearts were perfused with Krebs-Henseleit bicarbonate buffer containing 0, 4, 16, 64 and 100 nM concentrations of the above dihydropyridines for 15 min. Global ischemia was then induced by terminating the aortic flow for 30 min at 37 degrees, followed by 30 min of reperfusion. Left ventricular (LV) functional (LV developed pressure, its first derivative and coronary flow) and biochemical parameters (creatine kinase release) were monitored prior to ischemia and during reperfusion. In separate group of hearts, intracellular free Ca2+ ([Ca2+]i) was monitored with an intracellular calcium analyzer using a fluorescent Ca2+ indicator (Fura-2 AM). Tissue Ca2+ was also measured by atomic absorption spectroscopy after perfusing the hearts with ion-free cold buffer to wash out extracellular Ca2+. Significant recovery of the coronary flow was observed in all hearts treated with a high concentration (100 nM) of DHPs compared with the control group (P < 0.05), while a lower dose of nisoldipine (16 nM) and nifedipine (64 nM) also improved the coronary flow effectively. Reduction of myocardial creatine kinase release and improvement of the recovery of LV developed pressure, dp/dtmax, were achieved by DHPs in a concentration-dependent manner. A higher concentration of DHPs also decreased the formation of myocardial thiobarbituric acid reactive substances, although these compounds did not possess direct free radical scavenging effects in vitro. Tissue Ca2+ content was reduced significantly in treated groups. The rise of [Ca2+]i during ischemia and reperfusion appeared to be attenuated by these DHPs. The concentration-response study of the three DHPs showed the effective concentrations for reducing [Ca2+]i to be 16, 64 and 100 nM nisoldipine, nifedipine and nimodipine, respectively, in this experimental setting. The above results indicate that pretreatment with DHPs can attenuate the myocardial reperfusion injury by modulating Ca2+ overloading and decreasing the susceptibility of the membrane to free radical attack. PMID- 8466554 TI - The reversal of experimental cyclosporin A nephrotoxicity by thromboxane synthetase inhibition. AB - The ability of thromboxane synthetase inhibition to reverse acute cyclosporin A (CsA)-induced nephrotoxicity in the rat was investigated. CsA administration (50 mg/kg/day p.o. for 14 days) to male Sprague-Dawley rats caused a significant 50% decline in creatinine clearance rates, an increase in N-acetyl-beta-D glucosaminidase (NAG) enzymuria and renal tubulointerstitial damage by day 14. These changes were associated with a 5-6-fold increase in urinary thromboxane B2 excretion (from pretreatment values of 28.1 +/- 7.9 to 122.6 +/- 38.9 and 165.8 +/- 39.0 eta g/24 hr body weight on days 7 and 14, respectively). Excretion rates of 6-keto-prostaglandin F1 alpha and prostaglandin E2 were, however, unaffected by CsA administration. Co-treatment with a thromboxane synthetase inhibitor (CGS 12970; 8-[3-methyl-2-(3-pyridyl)-1-indolyl]-octanoic acid) from day 7 (10 mg/kg/day) normalized thromboxane B2 excretion, resulted in creatine clearance rates which were similar to pretreatment values on days 10 and 14, reduced NAG enzymuria on day 10 and prevented acute proximal tubular vacuolation. However, the severity of chronic CsA nephrotoxicity, namely chronic tubular damage and microcalcification at the corticomedullary junction, was not diminished by the thromboxane synthetase inhibition. These results demonstrate that (i) elevated thromboxane synthesis plays an important role in the development of acute CsA nephrotoxicity and (ii) that different and/or additional mechanisms are involved in the pathogenesis of chronic nephrotoxicity. PMID- 8466555 TI - Aromatic diamidines are reversible inhibitors of porcine kidney diamine oxidase. AB - The inhibitory ability of aromatic diamidines has been studied on porcine kidney diamine oxidase. The reversibility of drug-protein interactions has been tested by means of exhaustive dialysis experiments, showing in all cases a reversible binding pattern. Ki values obtained by means of Lineweaver-Burk plots were: stilbamidine 12 microM, 2-OH-stilbamide 8.5 microM, phenamidine 4 microM, propamidine 8 microM, dibromopropamidine 4.9 microM and amicarbalide 12 microM. PMID- 8466556 TI - Audiology for clothing? PMID- 8466557 TI - Let's use the right words. PMID- 8466558 TI - SPECT over PET? PMID- 8466559 TI - The civil right to speech. PMID- 8466560 TI - Child care: a challenge for the nineties. PMID- 8466561 TI - Activities to encourage speech and language development. PMID- 8466562 TI - Reinnervation of the cutaneous part of the free fibula osteocutaneous flap for reconstruction of the phallus. PMID- 8466563 TI - The cochlear implant and the deaf community. PMID- 8466564 TI - Laparoscopic inguinal hernioplasty. PMID- 8466565 TI - Valproate versus carbamazepine for seizures. PMID- 8466566 TI - Predisposing factors for severe, uncontrolled hypertension in an inner-city minority population. PMID- 8466567 TI - Suicidal ideation and young adults. PMID- 8466568 TI - "Chordal" preservation during mitral valve rereplacement. PMID- 8466569 TI - Treatment of atelectasis of the right upper lobe with a J-shaped catheter. PMID- 8466570 TI - Age effects of radiation-associated neurotoxicity in children. PMID- 8466571 TI - Nitrous oxide and fertility. PMID- 8466572 TI - The long-QT syndrome. PMID- 8466573 TI - Sex on the brain. PMID- 8466574 TI - Monitoring cyclosporine in liver-transplant recipients. PMID- 8466575 TI - Critical comparisons of alternative therapies for ectopic pregnancy! PMID- 8466576 TI - Detection of streptococcal antigens: arguments for and against testing in primary care offices. PMID- 8466577 TI - Pap smear provision in general practice. PMID- 8466578 TI - Prevalence and risk factors of iron-deficiency in women of Chukotka. AB - A study of iron deficiency states (IDS) in Chukotkan native women aged 20-59 years revealed a relatively high prevalence of 36.4%. The prevalence of anemia was 5.6%. Some risk factors of IDS have been defined including frequent deliveries, prolonged lactation and also some peculiarities in the nutrition of these women. PMID- 8466579 TI - The Keewatin Health Assessment Study, NWT, Canada. PMID- 8466580 TI - The Chukotka Chronic Diseases Study, Chukotka, Russia. PMID- 8466582 TI - Human exposure to environmental hazards in the Arctic. PMID- 8466581 TI - The Sante Quebec Cree and Inuit Surveys, Quebec, Canada. PMID- 8466583 TI - Plans for the Greenland Health Survey. PMID- 8466584 TI - Patterns of patient attendance and dental service utilization in northern Labrador 1985-1989. AB - The purpose of the present study was to identify patterns of dental patient attendance and service utilization using both epidemiological and service record data from six satellite clinics in Northern Labrador, Canada, between 1985-1989. Baseline attendances were derived for the region from the analysis of 1985-1988 data, the period prior to the introduction of a non-insured health benefit scheme. The results demonstrated that females and persons under the age of 21 years frequented the dentist the most. The effects of this non-insured health benefit scheme introduced in January 1989, was then compared to the baseline pattern of attendance. This dental coverage removed all financial barriers for dental treatment for a population of Inuit origin in this northern area (or 91% of the population). An increase in the uptake of all dental treatments by 10-40%, and a doubling of fillings and denture treatments was observed. About 7% more patients frequented the dentist in 1989. Attendances of the middle-aged and elderly patients increased by 4%. Mean number of appointments per person per year increased from the baseline level of 1.8 to 2.5. The largest increase in population attendances was observed in Hopedale, while Nain remained the community with the best attendance record. No better monthly patterns of attendance were identified for 1989 compared to the baseline. Future studies should continue to evaluate changes in treatment needs, demands and service utilization in the area on a longitudinal basis. There is also a need for more literature on patterns of dental attendances in northern areas. PMID- 8466585 TI - Temporal changes in superoxide dismutase, glutathione peroxidase, and catalase levels in primary and peri-ischemic tissue. Monosialoganglioside (GM1) treatment effects. AB - Time-dependent changes in levels of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPOD), and catalase (CAT) after cortical focal ischemia in rat indicate that: (1) primary and peri-ischemic tissues differ in both rate and the magnitude of oxyradical-induced ischemic injury, and (2) ischemic tissue remains vulnerable to oxyradical damage as long as 72 h after ischemia since the antioxidant enzyme levels remain at or below basal levels. After 72 h, the increased levels of these enzymes are sufficient to protect tissue against oxyradical damage. GM1 ganglioside (10 mg/kg, im) further increased the already elevated levels of the enzymes after ischemia, thereby indicating the GM1 treatment increases the capacity of ischemic tissue to protect against oxyradical injury. PMID- 8466586 TI - Regional lipid composition in the rat brain. AB - The lipid composition of the brain is of great importance to its metabolism and function. Although much research has been done on regional brain lipid composition, studies usually suffer from limited brain regions or from limited lipids analyzed. We modified a previously described method for the separation of brain phospholipids and glycolipids, improving the separation and sensitivity of the method. Using this modified method, we measured the lipid composition of the frontal and entorhinal cortices, the hippocampus, basal ganglia, cerebellum, and medulla oblongata of five rats under nitrous oxide analgesia. Total lipid content was highest (p < 0.05) in the medulla oblongata (111.0 +/- 6.0 mg/g wet brain, X +/- SD) followed by the hippocampus (72.6 +/- 2.8), cerebellum (62.7 +/- 4.6), basal ganglia (62.6 +/- 1.5), frontal cortex (57.7 +/- 2.1), and entorhinal cortex (53.3 +/- 1.9). The areas with higher total lipid content (p < 0.05) also had higher percentages of cerebrosides (18.6 +/- 2.2 in the medulla oblongata vs 8.3 +/- 1.2 in the frontal cortex) and 40 to 50% lower levels of phosphatidylcholine and phosphatidylinositol. The relation between the ratio of cerebrosides plus sulfatides to phosphatidylcholine and the total lipid content indicates that differences in brain lipid composition between regions are attributable to their relative gray/white matter content. PMID- 8466587 TI - Autoradiographic study on dopamine uptake sites and their correlation with dopamine levels and their striata from patients with Parkinson disease, Alzheimer disease, and neurologically normal controls. AB - An autoradiographic study of labeled mazindol binding to presumed dopamine (DA) uptake sites in the striatum was done in 7 Parkinson (PD), 6 Alzheimer (AD), 1 Huntington disease (HD), and 4 neurologically normal cases. Large and significant decreases of specific binding were found in PD in both caudate (to 32% of control) and putamen (to 16%), with no significant effect in AD or HD. Nonspecific binding was a large proportion of total binding in all cases. In the 12 cases where both binding data and DA levels were available, they showed highly significant linear correlations in both caudate and putamen. Autoradiographic studies on D1, D2, and muscarinic binding sites in the PD, AD and control striata revealed no significant group differences. PMID- 8466588 TI - Brain levels of neuropeptide Y in experimental pneumococcal meningitis. AB - Neuropeptide Y (NPY), which is found in high concentrations in several regions of the brain including nuclei of the brain stem and in nerve fibers surrounding cerebral vessels, has been proposed to play a role in regulating cerebral blood flow (CBF) and systemic vegetative functions. Since CBF is altered during meningitis, we examined whether NPY concentrations changed in various regions of the rabbit brain in response to experimental pneumococcal meningitis. Changes were most pronounced in the medulla, where NPY concentration increased threefold after 48 h of infection. Concomitantly, there was an increase in NPY immunoreactive fibers surrounding small vessels in the dorsolateral medulla, especially in the nucleus tractus solitarius. These results suggest that NPY may play a role in inducing some of the hemodynamic changes seen during pneumococcal meningitis. PMID- 8466589 TI - Immunohistochemical study of alpha 2 macroglobulin receptor in Alzheimer and control postmortem human brain. AB - Localization of the alpha 2 macroglobulin receptor (alpha 2MR) was studied in postmortem human brain tissue of Alzheimer disease (AD) and age-matched control cases with a monoclonal antibody (A2MR alpha 2) to the receptor. In control cases alpha 2MR was detected in neurons, glia, and some capillaries. Neuronal staining was most conspicuous in the hippocampus and entorhinal cortex. In AD, alpha 2MR immunoreactivity was enhanced. The staining intensity of some neurons was increased, as was the number of positive glial cells. In addition, senile plaques, tangles, and dystrophic neurites were strongly stained. These results suggest that alpha 2MR is involved in AD pathology. PMID- 8466590 TI - Urinary excretion of MHPG and normetanephrine in attention deficit hyperactivity disorder. AB - Twenty-four-hour excretion (expressed per gram of creatinine) of the norepinephrine metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NME) was measured in children with attention deficit hyperactivity disorder (ADHD) and in normal subjects matched for age and education. In contrast to findings with Tourette syndrome patients, in the ADHD patients there was no significant difference in excretion of MHPG and NME from control values. PMID- 8466591 TI - Hypoxia induces different responses of striatal high- and low- affinity dopamine uptake sites. AB - The dopamine (DA) uptake over a concentration range from 0.03 to 100 microM was studied in S1 fractions of the rat striatum prepared from control rats and those exposed for 14 h to hypobaric hypoxia. The uptake exhibited non-Michaelis-Menten kinetics, which were evaluated by applying an equation assuming two transport sites. The high-affinity uptake site was characterized by an apparent Michaelis Menten constant of 0.47 microM and an apparent maximal transport rate of 113 pmol/mg protein/30 s. The respective constants of the low-affinity uptake site were 52.8 microM and 1490 pmol/mg protein/30 s. One hour after hypoxia kinetic constants of the high-affinity uptake were unchanged but the maximal transport rate of the low-affinity uptake was increased by 50%. The elevated low-affinity uptake capacity may represent a means of adaptation to hypoxia allowing a faster removal of high extracellular concentrations of DA. PMID- 8466592 TI - The interaction of insulin and angiotensin II on the regulation of human neuroblastoma cell growth. AB - This laboratory has previously reported that angiotensin II is a growth factor for human SH-SY5Y neuroblastoma cells, and that a variety of converting enzyme inhibitors and angiotensin II antagonists reduce thymidine incorporation into the DNA of these cells. In the present study, insulin, at 5 micrograms/mL, was found to stimulate thymidine incorporation in SH-SY5Y cells. The insulin effect was only partially inhibited by the converting enzyme inhibitors enalapril, quinapril, and quinaprilat, whereas it was markedly or totally blunted by the angiotensin II antagonists DuP753 and PD123177. In additional studies, IGF-1 (50 ng/mL) significantly stimulated thymidine incorporation into these cells in a fashion indistinguishable from that of insulin. Taken together, these studies are consistent with the suggestion that insulin at high concentrations and IGF at low concentrations enhance the proliferative response of these cells to angiotensin II. The differential effects of converting enzyme inhibition and angiotensin II antagonism on cell proliferation could be explained if converting enzyme inhibition results in low, but effective, levels of angiotensin II in the culture medium, whereas the angiotensin II antagonists effectively block angiotensin II at its receptor. Finally, in this system, both the AT1 receptor blocking agent DuP 753 and the AT2 receptor blocking agent PD123177 appear to be effective. PMID- 8466593 TI - Accumulation of exogenous polyamines in gerbil brain after ischemia. AB - Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [14C]spermine was transiently increased after ischemia, peaking at 150% of control by 12-13 h and subsiding by 24 h. Intravenous injections of [3H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that: 1. Active cellular uptake of spermine is transiently increased early after ischemia; 2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and 3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia. PMID- 8466594 TI - Polyamines in rat brain extracellular space after ischemia. AB - This article reports measurements of extracellular polyamines in rat brain. Microdialysis probes were implanted in the striatum and microperfusion samples were collected before, during, and after transient (20 min) global ischemia. Polyamine levels in microperfusates were measured by reverse-phase high performance liquid chromatography after precolumn derivatization. No significant changes in extracellular polyamines were detected for up to 3 h following ischemia. We conclude that extracellular levels of polyamines (1) are comparable to the low levels in other extracellular compartments, and (2) do not change during the initial period of reperfusion, the period most critical for neuron survival after ischemia. PMID- 8466595 TI - Detailed characterization of the biological activities of recombinant human nerve growth factor expressed in Chinese hamster ovary cells. AB - The biological activities of recombinant human nerve growth factor (rhNGF) produced by Chinese hamster ovary (CHO) cells that were transfected with human NGF gene were investigated in vitro and in vivo. rhNGF showed the same immunoreactivity as mouse NGF (mNGF) in a highly sensitive two-site enzyme immunoassay system employing mouse monoclonal antibody against mouse beta-NGF (MAb 27/21) for both the primary and the secondary antibodies. In PC12 cells, rhNGF promoted neurite extension and induced acetylcholinesterase (AChE) with the same potency as mNGF, showing an ED50 of 10-20 ng/mL. In fetal rat septal neurons cultured on a feeder layer of astroglial cells, rhNGF promoted survival and neurite extension as well as an increase in choline acetyltransferase (ChAT) activity and acetylcholine (ACh) content. At a maximal effective concentration of 30 ng/mL, rhNGF promoted a 1.4-, 2.8-, and 4-fold increase in surviving cell number, ACh content, and ChAT activity, respectively. rhNGF was five times more potent than mNGF for the increase in ChAT activity and ACh content showing an ED50 of 0.5 ng/mL, although the maximal response was the same for the two NGFs. Transection of the fimbria-fornix resulted in a loss of AChE-positive cells in the medial septum (MS) and vertical limb of the diagonal band of Broca (VDB). The administration of rhNGF or mNGF (3 or 30 micrograms in gel form) attenuated the loss of AChE-positive cells; rhNGF was as potent as or even more potent than mNGF. Radio frequency lesion of the basal forebrain (BF) including the nucleus basalis magnocellularis (NBM) resulted in severe impairment of memory and/or learning in passive avoidance and Morris' water maze tasks. Repeated injection of rhNGF (5 micrograms x 5 over 2 wk) into the lateral ventricle ameliorated the behavioral impairment in the water maze task but not in passive avoidance. rhNGF treatment increased ChAT activity in the frontal cortex and even in other subregions of the cerebral cortex where ChAT activity was not decreased by BF lesion. These results indicate that human NGF can be measured in an enzyme immunoassay system using monoclonal antibody against mNGF (MAb 27/21) and that rhNGF has potent biological activity, comparable to or greater than mNGF, both in vitro and in vivo. PMID- 8466597 TI - The nature of public health after reform. AB - Many of the pressures now building to reform the American health care system can be traced to an unfortunate fragmentation of the health professions, notably between medicine and public health. Medicine has advanced strikingly in its curative potential in recent decades, but for that very reason has fallen prey to hubris, as technology has outpaced overall strategies of care. Public health offers counterbalance to this effect in that it stresses a population-based perspective on medical care and underscores the importance of prevention in any rational, comprehensive system devoted to the health of the public. Critical elements that must be factored into any major restructuring of the present costly health care arrangements include provision for universal access, enhancement of preventive and primary care capabilities, and education of the public about their health status and its maintenance in such ways that they can become informed collaborators in their overall care. Enhanced appreciation of behavioral cofactors in the etiology of many diseases will play an important role in that education of the public, but it must be achieved in ways that are nonjudgmental lest it be counterproductive to the overall goals of prevention and compassionate care. PMID- 8466596 TI - PC12 cells release stimulatory factors after transfection with beta/A4-C-terminal DNA of the Alzheimer amyloid precursor protein. AB - The beta/A4 region of the amyloid precursor protein (APP) accumulates in brains of victims of Alzheimer disease (AD) where it is a major component of senile plaques. We examined the pathophysiological consequences of overexpression of the beta/A4-C-terminal DNA in PC12 cells. Serum-free conditioned media (SFCM) from positive transfectants stimulated control PC12 cells to extend neurites and increase in size. Unlike the factor that affected cell size, neurite lengthening activity was significantly decreased after immunoabsorption with anti-beta/A4 monoclonal antibodies (MAb) and changes in pH. The data support the view that among the consequences of beta/A4-C-terminal DNA overexpression in PC12 cells is the release of factors that stimulate nontransfected cells to undergo morphological transformations that include differentiation to a neuronal phenotype. It is hypothesized that similar activities that may contribute to the molecular pathophysiology of the disorder may be present in the AD brain. PMID- 8466598 TI - Beyond multiple-choice questions and essays: the need for a new way to assess clinical competence. AB - This essay reviews the influence that research on psychological processes in clinical reasoning has had upon the characteristics and formats of licensing examinations such as the new United States Medical Licensing Examination (USMLE) and its predecessors, emphasizes the implications of such research for the assessment of clinical competence at all levels of medical education, and proposes a challenging new direction for educational research that could make clinical assessment more effective. Specifically, (1) factors are discussed that support the continued judicious use of multiple-choice questions (MCQs); and (2) emphasis is given to the need to assess the clinician's ability to analyze controversial clinical situations, where no single answer is agreed upon as "most nearly correct," for even though essay questions and oral examinations are better suited than MCQs to assess such questions, they have been replaced by MCQs largely because of problems of consistency in grading, breadth of domain sampling, and cost. Because of these limits on essays and oral examinations, a program of educational research is advocated to develop a test format that can effectively assess the clinician's abilities to deliberate among alternatives, to recognize the role of values and preferences in decisions, and to weigh risks and benefits. Just how much this new tool could be used for national certification and licensing examinations would have to be determined, but it is important that some component be included to signal to educators and new physicians that medical practice is, at least in part, concerned with matters for which final answers are not available. PMID- 8466600 TI - Elements of an effective medical school curriculum committee. PMID- 8466599 TI - Ethics in a short white coat: the ethical dilemmas that medical students confront. AB - Many existing ethics curricula fail to address the subtle yet critical ethical issues that medical students confront daily. The authors report on the kinds of dilemmas students face as clinical clerks, using cases that students submitted in 1991-92 during an innovative and well-received ethics class given at a tertiary care hospital as part of the internal medicine clerkship. Analysis of these cases reveals that many dilemmas are intimately tied to the student's unique role on the medical health care team. Recurring themes included the student's pursuit of experience, differing degrees of knowledge and ignorance among team members, and dealing with disagreement within the hierarchical authority structure of the medical team. The authors conclude that some components of ethical education must be participant-driven and developmentally stage-specific, focusing more attention on the kinds of ethical decisions made by medical students as opposed to those made by residents or practicing physicians. PMID- 8466601 TI - Saying what you mean and meaning what you say: coupling biomedical terminology and knowledge. PMID- 8466602 TI - Managed competition. PMID- 8466603 TI - Academic medical centers have a major role in preventing violence. PMID- 8466605 TI - Medical students' well-being: a necessary component of reform. PMID- 8466604 TI - Is declining class size related to the shortage of family medicine practitioners? PMID- 8466606 TI - Chief residents' career motives and perceived constraints. PMID- 8466607 TI - A method for selecting a site for a rural residency program. PMID- 8466608 TI - The effect of training on the management of asthma by family physicians. PMID- 8466609 TI - Fostering a new relationship between departments of medicine and teaching hospitals. PMID- 8466610 TI - The declining interest of medical school graduates in generalist specialties: students' abandonment of earlier inclinations. PMID- 8466611 TI - Influence of longitudinal primary care training on medical students' specialty choices. AB - BACKGROUND: At the University of South Florida College of Medicine, a program designed to give students four years of primary care training began in 1983. As of 1992, six classes that included program participants had graduated. The present study examined the effect of the program on the participants' choices of specialty by comparing their choices with those of other graduates. METHOD: Each year program volunteers were solicited from a class size of about 96 freshmen. Of the 201 volunteers from the classes of 1987-1992, 93 were randomly selected to participate in the program. The participants received primary care education one half-day per week in a community-based clinical setting. The specialty choices of the 543 graduates from 1987-1992 were determined from the National Resident Matching Program and were divided into primary care (family practice, internal medicine, pediatrics); surgery, obstetrics-gynecology, and psychiatry; and other (high-technology specialties). Comparisons were made (1) between volunteers and nonvolunteers and (2) between volunteers who were participants and those who were not. The Z-test was used, with alpha set at .01. RESULTS: Significantly more volunteers--with no difference between participants and nonparticipants--matched with primary care specialties, and more volunteers were women. Significantly more nonvolunteers matched with high-technology specialties--again, no difference between participants and nonparticipants. CONCLUSION: The program did not seem to influence the students' specialty choices, because students interested in participating--regardless of whether they actually participated--were more likely to match with primary care specialties and were more likely to be women. PMID- 8466613 TI - Further psychometric evaluations of a class-ranking model as a predictor of graduates' clinical competence in the first year of residency. AB - PURPOSE: To investigate further the psychometrics of a class-ranking model in which a weight of one-third was assigned to performance measures in basic sciences and a weight of two-thirds to ratings on six core clerkships. METHOD: The first part of the study involved 215 graduates of Jefferson Medical College who--based on the ranking model--had been in the top and bottom quarters of the classes of 1991 and 1992. Six faculty, who did not know the graduates' ranks but were familiar with their performances and characteristics, were asked to judge the graduates' potential to become competent physicians. The graduates' ranks according to the model were then compared with the ratings they received from the faculty. The second part of the study investigated whether there was a linear relationship between class ranks and ratings of postgraduate competence, by using directors' ratings of the data-gathering skills of 598 graduates (1986-1990) at the end of their first year of residency. RESULTS: A concordance rate of 85% was obtained between the graduates' ranks and the ratings they received from the medical school faculty, which supports the criterion-related validity of the ranking model. In addition, class ranks were linearly related to ratings of postgraduate competence. However, women and graduates who had been low achievers in medical school were less likely to have given permission for collecting postgraduate ratings, which led to range restriction and a possible underestimation of the validity of the model. CONCLUSION: The psychometric evidence supports the class-ranking model, but other schools should exercise caution in employing the model until they accumulate evidence from data obtained from their own students. PMID- 8466612 TI - Medical students' clinical self-assessments: comparisons with external measures of performance and the students' self-assessments of overall performance and effort. AB - PURPOSE: To find predictors of students' initial self-assessments of their clinical performances, the predictive value of their self-assessments, and factors that relate to their final self-assessments. METHOD: Of the 142 third year students at the University of Michigan Hospital in 1988-89, 137 (96%) completed a self-assessment questionnaire on the first day of their internal medicine clerkship and a slightly expanded questionnaire on the last day. The questionnaires asked the students to use Likert-type scales to rate their abilities regarding clinical skills, use of knowledge in the clinical setting, and discharge of patient care responsibilities. Also collected were data on the students' performances as measured externally: college grade-point averages; standardized examinations taken before, during, and after the clerkship; and ratings given the students by the faculty and residents with whom they worked in the clerkship. Pearson product-moment correlations were then calculated between the students' self-assessment ratings and their scores on the external measures of performance. RESULTS: Weak to absent correlations were found between prior performance measures and initial self-assessments. The lower-performing students, as measured by college grade-point averages and Medical College Admission Test scores, tended to rate their performances higher than did their peers at initial self-assessment. IN contrast, the higher-performing students rated themselves lower than would be warranted given their prior performances. There were significant increases in the initial self-assessments as the year progressed and the students entered the clerkship after having had more experience. The correlations between the students' final self-assessments and the ratings by faculty and residents were generally weak. The strongest (.267, p < or = .001) concerned the students' medical knowledge. In addition, there was a moderate correlation (.413, p < or = .001) between the students' self-assessments of how hard they had worked and their self-assessments of overall performance. CONCLUSION: The findings in this study were similar to those of previous studies in that they showed relatively poor agreement between external measures of students' performances and students' self-assessments of their performances. PMID- 8466614 TI - Comparing clerkship sites in a community-based medical school by evaluating students' undergraduate and postgraduate performances. AB - BACKGROUND: Studies have generally found clinical training sites within the same clerkship to be comparable regarding students' performances--by using undergraduate measures in individual clerkships at medical schools with university hospitals. The present study examined performance comparability among sites within two clerkships in a community-based medical school and used both undergraduate and postgraduate measures. METHOD: The participants were the 349 graduates from the classes of 1988-1991 at Wright State University School of Medicine who took an internal medicine clerkship (332 of the graduates, in five principal combinations of sites) and a general surgery clerkship (349 at six sites). The undergraduate measures were final percent scores for the clerkships and subtest and total scores on the National Board of Medical Examiners (NBME) Part II examination. The postgraduate measures were supervisors' ratings from the first year of residency (210 graduates) and total score on the NBME Part III (212). Univariate analysis of variance and Tukey's multiple-range test were used for the comparisons. RESULTS: The only statistically significant difference among sites was for the medicine clerkship and involved only one undergraduate measure, the clerkship score (and the differences were slight, less than four percentage points). CONCLUSION: Virtually no differences in the students' performances on the undergraduate and postgraduate measures were found among sites for the two clerkships. PMID- 8466615 TI - Effects of student gender and standardized-patient gender in a single case using a male and a female standardized patient. AB - BACKGROUND: In previous studies assessing the effects of student gender, standardized-patient (SP) gender, and their interaction on multiple-station examinations of clinical competence, SP gender was confounded with cases, that is, male SPs were used for some cases and female SPs for others. The authors conducted two studies to investigate the effects of gender on a single case by using a male SP and a female SP for the same case. METHOD: Both studies involved one SP case in a comprehensive clinical evaluation used to assess fourth-year students at the end of a required ambulatory care clerkship at Saint Louis University School of Medicine in 1990-91 and 1991-92. In Study 1, 45 students in four rotations saw the same male SP; 42 students in three other rotations saw the same female SP. In Study 2, 69 students in six rotations were randomly assigned either the male SP (28) or the female SP (41) within the same rotation. For each study, to determine the interaction of student gender and SP gender as well as their main effects, analyses of variance were performed on the students' history taking and physical examination scores and communication skills ratings. RESULTS: Neither study showed a significant interaction of student gender and SP gender on history taking, physical examinations, or communication skills. CONCLUSION: The findings of both studies suggest that the interaction between student gender and SP gender, unconfounded by case content, had no effect on the students' scores and ratings. PMID- 8466616 TI - Critical thinking in preclinical course examinations. AB - PURPOSE: To examine the relationship between preclinical medical school course examinations and critical-thinking skills by correlating examination results with the Watson-Glaser Critical Thinking Appraisal (WGCTA), an 80-item critical thinking inventory. METHOD: The 196 students in the class of 1993 at the University of Texas Southwestern Medical Center at Dallas Southwestern Medical School were given the WGCTA during the second half of their freshman year. A composite WGCTA score and five subtest scores were calculated for each student. The course examinations were 25 tests, each with a majority of multiple-choice items, from courses given during the first two years of the school curriculum. The students' undergraduate grade-point average (GPAs), medical school GPAs, and Medical College Admission Test (MCAT) scores were also included in the analysis. Pearson product-moment correlations were calculated between the students' WGCTA scores and their examination scores, MCAT scores, and GPAs. RESULTS: Sixteen of the examinations--in the behavioral sciences, psychiatry, ethics, pathology, introduction to clinical medicine, genetics, endocrinology, and cell biology--had significant positive correlations with the WGCTA, as did MCAT scores and first year GPAs. Correlations were more robust with the WGCTA subscales for interpretation (18 examinations), evaluation of arguments (15), and deduction (13), and less robust with the subscales for inference (7) and recognition of assumptions (3). CONCLUSIONS: The results suggest that objective multiple-choice examinations can at least partially reflect critical-thinking skills. PMID- 8466617 TI - A twelve-year profile of students' SAT scores, GPAs, and MCAT scores from a small university's premedical program. AB - PURPOSE: To determine whether significant correlations existed among quantitative and qualitative predictors of students' academic success and quantitative outcomes of such success over a 12-year period in a small university's premedical program. METHOD: A database was assembled from information on the 199 graduates who earned BS degrees in biology from Barry University's School of Natural and Health Sciences from 1980 through 1991. The quantitative variables were year of BS degree, total score on the Scholastic Aptitude Test (SAT), various measures of undergraduate grade-point averages (GPAs), and total score on the Medical College Admission Test (MCAT); and the qualitative variables were minority (54% of the students) or majority status and transfer (about one-third of the students) or nontransfer status. The statistical methods were multiple analysis of variance and stepwise multiple regression. RESULTS: Statistically significant positive correlations were found among SAT total scores, final GPAs, biology GPAs versus nonbiology GPAs, and MCAT total scores. These correlations held for transfer versus nontransfer students and for minority versus majority students. Over the 12-year period there were significant fluctuations in mean MCAT scores. CONCLUSION: The students' SAT scores and GPAs proved to be statistically reliable predictors of MCAT scores, but the minority or majority status and the transfer or nontransfer status of the students were statistically insignificant. PMID- 8466618 TI - A continuous quality improvement cycle for teaching the identification of psychosocial problems to general internal medicine residents. AB - PURPOSE: To study a continuous quality improvement (CQI) cycle intended to enhance general internal medicine residents' identification of psychosocial problems in an ambulatory-care setting. METHOD: From 1986 through 1990, the authors compared two groups of comprehensive examinations of patients by 34 residents at the University of Vermont College of Medicine before and after the implementation of a CQI cycle. After data on the first group of 17 residents' examinations of patients had been retrospectively audited by a clinical social worker, the CQI cycle was developed for the next group of 17 residents' examinations to reinforce the importance of psychosocial problems in primary care and the use of diagnostic case-finding instruments, flow sheets, and real-time feedback from social workers to the residents on their performances, according to accepted predefined specifications. The t-test was then used to measure the difference in the residents' performances between the two groups of examinations. RESULTS: The CQI intervention resulted in a statistically significant (p < .05) improvement in performance: an increased rate of residents' identifications of patients with psychosocial problems, from 72% (36 of 50 patients) to 85% (140 of 165 patients). CONCLUSION: That the CQI cycle resulted in improved performance suggests that an effective psychosocial training program for residents in ambulatory primary-care general internal medicine can be organized around CQI and a problem-oriented system of care. PMID- 8466619 TI - Colorado's decentralized medical education to increase the number of graduates practicing primary care in rural areas. PMID- 8466620 TI - Comparing the teaching of physical diagnosis in a primary care setting and a hospital setting. PMID- 8466621 TI - Participants' perceptions versus actuality in achieving the goals of problem based learning. PMID- 8466622 TI - A simple ambulatory-care experience and students' residency choices and attitudes toward general internal medicine. PMID- 8466623 TI - A brief measure of psychological androgyny for use in predicting physicians' decision making. PMID- 8466624 TI - Using active participation in a consensus conference to enhance its influence on physicians' clinical behavior. PMID- 8466625 TI - Proteoglycans on endothelial cells present adhesion-inducing cytokines to leukocytes. AB - Leukocyte recruitment from the blood circulation into tissue is essential for effective immune responses, and is, consequently, carefully regulated. In this article Yoshiya Tanaka and co-workers describe a model in which proteoglycans on the luminal surface of endothelium capture pro-adhesive cytokines. These cytokines provide the adhesion-inducing signal to particular leukocyte subsets which initiates their transmigration. PMID- 8466626 TI - Sequence homologies between hsp60 and autoantigens. AB - The human heat shock protein (hsp) 60 shares sequence homology with a wide range of autoantigens including those of insulin dependent diabetes mellitus, Hashimoto's thyroiditis, glomerulonephritis, scleroderma, pemphigoid, rheumatoid arthritis, multiple sclerosis, chronic active hepatitis, primary biliary cirrhosis and Addison's disease. Here we show the extent of this homology and suggest that it contributes to autoimmunity through cross-reactivity between hsp60 and tissue-specific proteins containing similar epitope motifs. Differences between individuals in MHC class II may influence the selection of a particular hsp60 epitope and the corresponding target antigen that gives rise to an autoimmune disease. PMID- 8466627 TI - What is an idiotype? AB - Idiotypy is an important concept with significant practical implications for the manipulation of B- and T-cell clones. However, this potential depends on a correct identification of idiotypy and the development of appropriate reagents. Current knowledge of the structure and polymorphism within the Ig loci reveals that several idiotypic paradigms are based on isotypic or allotypic structures rather than supposed crossreactive idiotypes. PMID- 8466628 TI - Apoptosis. AB - Cell death can be accidental or programmed in a multicellular organism. Evidence supports the proposition that there is a 'suicide program' inherent in vertebrate cells which can be activated when the cell's death is desirable for the good of the rest of the community. The morphology of such death is usually that of apoptosis, rather than of necrosis. Here, John Cohen describes the changes of apoptosis, and discusses progress on the identification of regulatory mechanisms and genes. PMID- 8466629 TI - The tale of T cells. AB - The discovery of the thymus was perhaps the major milestone of contemporary immunology. Here Anthony Davies reflects on the events surrounding this discovery and puts into perspective the significance of those experiments today. PMID- 8466630 TI - Of furphys, and facts that are fugacious. PMID- 8466631 TI - Janus-faced tumor-associated macrophages. PMID- 8466632 TI - Antigen presentation by intestinal epithelial cells. PMID- 8466633 TI - Cell adhesion in the immune system. AB - Cell adhesion molecules have an important role to play in many facets of the immune system. At a recent meeting their role in leukocyte migration, inflammation, cancer metastasis and lymphocyte development was discussed. PMID- 8466635 TI - Immunologic infertility: a basic review. AB - Antisperm antibodies interfere with the human reproductive events and once they have been produced, antisperm antibodies bind to the spermatic surface and affect both the transport of spermatozoa and the interactions between the gametes. The formation of antisperm antibodies has still not been completely explained and the antigen map of the spermatic surface has not been yet established. The antibody levels in the serum generally do not reflect the immunoglobulin present in the secretions of reproductive tract and in the immunologic screening of the infertile couple we need of direct analysis of antisperm antibodies on the spermatic surfaces. We have many diagnostic procedures but actually very few therapeutic options: to improve the last question, a better understanding of the phenomena that lead to fertilization is imperative. PMID- 8466634 TI - [Correlational study between lymphocyte IgE markers: membrane CD23 (mCD23) and soluble CD23 (sCD23) in an atopic population]. AB - IgE has two types of receptors: high affinity RFc sigma I and low affinity RFc sigma II. The latter may be studied by flow cytometry by the membrane marker CD23 (mCD23), expressed on B and T cells, monocytes, macrophages, Langerhans cells, eosinophils and platelets. Soluble CD23 (sCD23) corresponds with the extracellular C terminal domain of mCD23. The aim of the study was to search for a correlation between the levels of mCD23 and sCD23, comparatively with IgE, eosinophils, eosinophil cationic protein (ECP) and to the cytokines IL2, IL4 and IL6. 78 patients took part in the study, divided into two groups: Group 1 = atopics (n = 61); Group 2 = controls (n = 17). The majority presented with rhinitis, asthma, atopic dermatitis isolated or associated. The results showed a highly significant correlation between mCD23 and sCD23 compared with the control group. There was also a statistically significant increase for mCD23, sCD23, cytokines IL2, IL4 and IL6, mediator ECP in parallel with eosinophils and total IgE. This study confirms amongst other things the rise in IL4 in atopy and the correlation between the level of ECP and that of eosinophils, and that there is an overall correlation between mCD23 and sCD23. PMID- 8466636 TI - [Vitamins and immunity]. AB - Nutritional status conditions immunity in man whom malnutrition is often associated with diminished immunocompetence and increased susceptibility to infection. Among micronutrients, vitamins A, C, E and carotenoids notably have special influence: they provide good cellular and tissular physiological behaviour; they also protect tissues against reactive oxygen species, and enhance immune response. PMID- 8466637 TI - [Apropos of 2 cases of latex allergy with isolated ocular expression]. AB - We present here two cases of latex allergy with ocular manifestations due to the use of condoms and the manipulation of rubber bands. In both cases the in vivo (prick tests) and the in vitro (RAST) testing were positive. In one of these two cases, the immunological tests performed in tears showed a local synthesis of latex specific IgE. PMID- 8466638 TI - [Pharmacologic study of the glucocorticoid activity of flunisolide compared with other steroids in the rat]. AB - Flunisolide (FLU), beclomethasone dipropionate (BDP) and its pulmonary metabolites beclomethasone monopropionate (BMP) and beclomethasone (B) were studied in rat for: their relative binding affinity (RBA) for the 5 classes of steroid receptors, their in vitro glucocorticoid activity on rat thymocytes, their in vivo glucocorticoid activity by oral route. These compounds displayed a strong RBA for rat lung, thymus and liver glucocorticoid receptors (FLU > or = BMP > BDP > or = B). They were also shown to have a moderate RBA for both mineralocorticoid and progestin receptors, while being devoid of any binding to androgen and oestrogen receptors. On rat thymocytes FLU exhibited the highest glucocorticoid activity (FLU > B > or = BMP > BDP). In rat oral FLU displayed a strong glucocorticoid activity with a slight first-pass metabolism as opposed to what has been reported in human. PMID- 8466639 TI - [Teldane update. Interview with Dr. Alfred Sabbah, chief of the immuno allergology laboratory of the C.H.U. d'Angers. Interview by Dr. Pierre Ceddaha]. PMID- 8466640 TI - Dual effects of cytokines in regulation of MHC-unrestricted cell mediated cytotoxicity. AB - Natural killer (NK) cells probably function as an early defense line against viruses, due to their ability to kill virus-infected cells without resorting to clonal proliferation of memory cells. NK cells are also capable of killing tumor cells. In both cases the killing is major histocompatibility complex (MHC) unrestricted. NK cells exhibit spontaneous activity but they are positively regulated by interferon (IFN) or indirectly by such IFN-inducers as viruses, bacterial products, poly (rl):(rC), and mitogens. Interleukin-2 (IL-2) has the ability to enhance NK activity in addition to its ability to generate lymphokine activated killer (LAK) cell activity. Recently, it was documented that other cytokines (e.g., IL-1, tumor necrosis factor (TNF), IL-6, and IL-12) are also involved in induction or enhancement of the cytotoxic activity of NK cells. Besides their "positive" regulation of NK activity, cytokines (in some cases the same cytokines) often act as "negative signals" for NK-mediated cytotoxicity. If NK susceptible target cells are exposed to IFN prior to NK cells, their sensitivity to NK activity is often markedly diminished. The mechanism by which IFNs (IFN-alpha, -beta and -gamma) affect the sensitivity of target cells to NK activity remains unknown, but it is clear that this function is not shared by other cell-mediated killing processes. The protective effect induced by IFN against NK activity is dependent on new mRNA and protein synthesis and can be abolished when target cells are incubated with combination of IFN and metabolic inhibitors or by chemotherapeutic purine or pyrimidine analogs. Class I MHC antigens have a central role in cell to cell interactions in the immune system. Because IFN has the ability to induce/increase class I MHC antigen expression, it has been suggested that class I MHC antigens act as "negative signals" of NK mediated cytotoxicity. Although many studies support this hypothesis, others present evidence for a lack of involvement of class I MHC antigens in mediating sensitivity to NK activity. Other cytokines have been tested for their ability to affect the sensitivity of target cells to NK activity, as well as their ability to enhance the cytotoxic activity of NK effector cells. Lymphotoxin (TNF-beta) increases target cell susceptibility to NK activity. On the other hand, IL-1, IL 2, IL-6, and TNF reduce the sensitivity of target cells to NK lysis, at least in some systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8466641 TI - The role of mast cells in inflammatory responses in the lung. AB - Human lung mast cells (HLMC), by virtue of their anatomic localization and release of potent chemical mediators, are well suited to produce characteristic pathophysiological inflammatory reactions in the lung. Much has been learned about the nature of these cells over the past 10 years, following the development of techniques to disperse them from lung tissue and ultimately purify them to near homogeneity. Recent work focusing on the origin, ultrastructure, proliferation, differentiation, heterogeneity, biochemistry of release, mediators, and pharmacological control of HLMC secretion is reviewed. Current knowledge of HLMC involvement in asthma and interstitial lung diseases, characterized by fibrosis, is summarized with an emphasis on potential areas of therapeutic intervention. PMID- 8466642 TI - Heat shock proteins in immune responses. AB - The assembly of functional MHC-I and MHC-II complexes is rapid, specific, and efficient. Recent advances in the area of antigen processing and presentation suggest that members of the heat shock protein (hsp) family facilitate the molecular events in the assembly process. Furthermore, hsps themselves have been shown to be the dominant antigens of a variety of pathogens as well as serving as targets of the immune system in healthy individuals. Hsps may play a fundamental role in immune responses, serving as an early warning to the host's immune system during the onset of infection. PMID- 8466643 TI - A bipartite activation domain is responsible for the activity of transcription factor HNF1/LFB1 in cells of hepatic and nonhepatic origin. AB - HNF1/LFB1 is a transcription factor that controls the expression of several liver specific genes. Previous in vitro experiments allowed us to identify two different regions in the carboxy-terminal portion of the protein responsible for most of the transcription activation potential: the first, ADI, between amino acids 546 and 628 and the second, ADII, between amino acids 281 and 318. To characterize the molecular anatomy of HNF1/LFB1 better, we have analyzed its trans-activating properties in vivo. Several HNF1/LFB1 deletion mutants were tested for their ability to induce transcription from HNF1/LFB1-dependent synthetic promoters in cells of hepatic and nonhepatic origin. These last recipient cells provide an HNF1/LFB1-deficient environment that is useful for a precise quantification of the recombinant protein. Our results confirm the importance of ADI and indicate that no activating property can be assigned to ADII in vivo. Moreover, a novel glutamine/proline-rich activation domain (ADIII) has been identified between amino acids 440 and 506. These findings are confirmed by domain-swapping experiments, carried out with the heterologous GAL4 DNA binding domain, which also show that the activity of each individual activation domain is influenced by combining adjacent HNF1/LFB1 sequences. The data presented indicate that HNF1/LFB1 transcription activating potential relies on a complex structure and also provide important clues to understanding the different functions exerted by transcription factors of this family. PMID- 8466644 TI - 5' structure and expression of human glucose-6-phosphate dehydrogenase mRNA. AB - The human glucose-6-phosphate (G6PD) cDNAs cloned from normal and carcinoma cells can encode 545-amino-acid residues starting from the first in-frame chain initiation codon. However, it was reported that the G6PD mRNAs of carcinoma cell lines were shorter and could encode only 515-amino-acid residues (Martini et al., 1986). We demonstrated the existence of two major G6PD mRNAs in normal reticulocytes, lymphoblasts, and hepatocytes by the primer extension analysis. The longer mRNA has a cap site at approx. nucleotide -166 and can encode 545 amino-acid residues, whereas the shorter mRNA has a cap site at approx. nucleotide -66, and encodes 515-amino-acid residues. These two naturally existing mRNAs (cDNAs) and an artificially truncated mRNA, which can encode the carboxy terminal 479-amino-acid residues of the subunit, were expressed in the in vitro reticulocyte and wheat germ systems and in the in vivo E. coli system. All three species of mRNA (cDNA) were efficiently translated and produced proteins with the expected molecular sizes. The peptide with 515 residues formed the catalytically active enzyme, but the 545-residue protein and the 479-residue protein were catalytically inactive. The larger 545-residue protein may correspond to the larger G6PD precursor observed in the rat. The extended amino-terminal region encoded by the larger mRNA contains the -Arg-Gly-Gly-Arg-Arg-Arg-Arg-sequence, which is conserved in the nucleotide-binding protamine family. PMID- 8466645 TI - Cytogenetic evidence of involvement of chromosome regions 15q12 and 12q15 in conditions with associated overgrowth. AB - Syndromes with associated overgrowth are poorly understood. Besides their mode of inheritance, nothing is known regarding the basic genetic alterations that lead to their abnormal phenotypic manifestations. The chromosome localization of the genes involved remains unknown for this group of syndromes, with the only exception being the Wiedemann-Beckwith syndrome. PMID- 8466646 TI - Induction of O6-methylguanine-DNA-methyltransferase and N3-methyladenine-DNA glycosylase in human cells exposed to DNA-damaging agents. AB - The inducibility of two DNA repair proteins, the O6-methylguanine-DNA methyltransferase (MGMT) and the N3-methyladenine-DNA-glycosylase (ANPG), was studied by measuring the protein activities and the transcription of the MGMT and ANPG genes in a human hepatoma cell line (LICH cells). The two protein activities are enhanced after treatment with a variety of DNA-damaging agents. They are maximum 72 hr after the inducing treatments and remain elevated for about 120 hr. This induction is abolished when the cells are grown in the presence of protein or RNA synthesis inhibitors. Northern blot analysis shows that the DNA-damaging agents increase to different extents the transcription of the MGMT or ANPG genes. The transferase activity is also increased by DNA damage in a human glioblastoma cell line (T98G cells), but is not significantly modified in human normal fibroblasts, suggesting that this repair activity enhancement might occur preferentially in transformed cells, as we have previously shown for cells of rat origin. Therefore, these increased repair activities may play an important role in removing the lethal N3-methyladenine residues, the promutagenic O6 methylguanine lesions, and the potentially lethal chloroethyl adducts formed by the nitrosoureas used in cancer chemotherapy more efficiently from the cellular DNA. PMID- 8466647 TI - Characterization of multiple transcription initiation sites of the ovine insulin like growth factor-I gene and expression profiles of three alternatively spliced transcripts. AB - Alternative splicing of ovine insulin-like growth factor-I (IGF-I) transcripts generates three different mRNAs. Class 1 and class 2 transcripts contain exons 1 and 2 spliced to exon 3, respectively. A novel IGF-I mRNA containing exon W is spliced to exon 3 and has been located upstream of exon 1. No in-frame methionine codon was present in exon W and therefore translation is proposed to initiate at the methionine codon present in exon 3. Using primer extension, transcription initiation sites were found 179, 336, and 368 nucleotides upstream of exon 1 and 86, 96, 131, and approximately 850 nucleotides upstream of exon 2. The locations of these transcription initiation sites are well conserved among mammalian and avian IGF-I genes. Expression of exon 1-, 2-, and W-specific transcripts was examined in brain, heart, kidney, liver, lung, skeletal muscle, and spleen from adult ewes or 75-day fetal lambs using a reverse transcriptase-polymerase chain reaction assay. Exon 1 transcripts were the most abundant and found in all fetal and adult tissues. Exon 2 transcripts were found in all tissues and were generally expressed the highest in adult liver. Exon W transcripts were also found to be expressed in all tissues examined. Thus, the three alternatively spliced ovine IGF-I transcripts were expressed in a variety of fetal and adult tissues. PMID- 8466648 TI - Structure of the rat catechol-O-methyltransferase gene: separate promoters are used to produce mRNAs for soluble and membrane-bound forms of the enzyme. AB - The enzyme catechol-O-methyltransferase (COMT) catalyzes the inactivation of catechol-containing molecules by methylation. The cDNAs for the rat and human COMT have recently been cloned and recombinant proteins expressed in prokaryotic and eukaryotic cells. We describe here the structure of the rat COMT gene and its 5'-flanking sequences. The gene spans at least 13 kb and is composed of 5 exons, the first one noncoding. The two ATG codons for the initiation of translation of the membrane-bound (MB-COMT) and soluble (S-COMT) forms of the enzyme reside in the second exon. The gene expresses two mRNA species of 1.6 kb and 1.9 kb that have different tissue distributions. The expression of the transcripts is regulated by at least two promoters, P1 and P2. The P1 promoter expresses the shorter transcript in a tissue-specific manner and is located between the ATG codons in the coding region of the longer transcript. The P2 promoter is constitutive and responsible for the expression of the longer transcript. The shorter 1.6-kb mRNA (S-mRNA) produces only the S-COMT polypeptide, whereas the longer 1.9-kb mRNA (MB-mRNA) is able to direct synthesis of both forms of the COMT enzyme. PMID- 8466649 TI - Characterization of the DNA-binding properties of the early growth response-1 (Egr-1) transcription factor: evidence for modulation by a redox mechanism. AB - The binding of the transcription factor early growth response-1 (Egr-1) to its specific DNA-binding sequence GCGGGGGCG occurs through the interaction of three zinc finger motifs. DNA binding by Egr-1 can be modified by alteration of reduction-oxidation (redox) state. Using gel retardation assays, we show that binding of Egr-1 protein is specific and is dependent on the presence of reducing agents in a dose-dependent manner. The zinc finger region is the domain subject to conformation changes by redox. Oxidized or metal-free Egr-1 does not bind. Nuclear extracts of several cell types contain a heat-sensitive factor(s) that induces the ability of Egr-1 protein to bind to DNA in otherwise suboptimal conditions containing insufficient reducing agent. This inducing activity may be replaced by Ref-1, a protein identified and characterized by Curran and co workers (Xanthoudakis and Curran, 1992). The possibility arises that the transcription-regulating activity of Egr-1 may be regulated by the redox state in the cell via factors such as Ref-1 that modulate its DNA-binding activity. PMID- 8466651 TI - [Opinions of Honduran adults about street children]. AB - The purpose of this study was to determine the beliefs parents of working children and business people have about two types of street children, those who work on the street and those who are abandoned and live on the street. In 1991 forty-nine parents of working children and 49 business people from Tegucigalpa were administered a questionnaire listing 36 beliefs about the lifestyles of abandoned and working children and causes of children adopting these ways of life. Among parents of working children, education was significantly lower and mothers were more likely to be single women than in the business people sample. There were many beliefs about the lifestyles of street children on which both groups agreed, but parents of working children held the youngsters more accountable for choosing to work or live in the street. Parents also seemed to be more aware of the health risks to both types of street children than business people who felt working children were at less risk than abandoned children. Business people perceived abandoned children to be victims of single parenthood and solvent abuse. A deeper exploration of the views held by families of street children may assist those seeking to help them. PMID- 8466650 TI - Mapping of a sequence essential for the nuclear transport of the Xenopus ribosomal transcription factor xUBF using a simple coupled translation-transport and acid extraction approach. AB - The amino acid sequences directing the nuclear transport of the RNA polymerase I transcription factor xUBF have been studied by a novel combination of in oocyte coupled translation-nuclear transport and selective HCl extraction. Synthetic mRNA was used to direct the translation of labeled xUBF and its mutants in microinjected oocytes. After manual dissection of nuclei and cytoplasm, labeled xUBF and mutants were isolated essentially pure by HCl extraction. Using deletion mutations, a sequence essential, but not necessarily sufficient, for nuclear transport was mapped to a 29-amino-acid segment lying between the most carboxy terminal putative HMG-box DNA-binding domain, HMG-box 5, and the highly acidic carboxy-terminal domain. It was shown that deletion of only 5 amino acids from this segment eliminated xUBF transport, and it could be deduced that at least 11 of the 29 amino acids were essential for nuclear transport. The segment of xUBF necessary for nuclear transport contains a sequence conforming to the bipartite nuclear transport motif consensus, but this sequence in itself was insufficient for nuclear transport. PMID- 8466652 TI - [Relations between health and development]. AB - The relationship between the health of a population and the state of development of a society is complex and varies over time. Throughout history, improved health has been one of the main benefits of development. This benefit results partly from an increase in income and partly from scientific progress in the fight against disease and disability. This second factor is increasingly important compared to simple economic growth. Reciprocally, health could be expected to have a favorable effect on development, although this effect is more difficult to detect. Nevertheless, health can be considered part of a society's capital stock, as long as the essential differences between this type of capital and physical capital are recognized. These differences, in turn, provide an insight into the health services market and, in particular, into the tendency to spend more and more resources on health. It is necessary to respect the intrinsic value of human capital, rather than focusing strictly on the economic productivity that may be derived from it, in order to prevent discrimination against children, the elderly, the poor, or the disabled. PMID- 8466653 TI - [The painful reality of street children]. PMID- 8466654 TI - Neonatal exogenous testosterone modifies sex difference in radial arm and Morris water maze performance in prepubescent and adult rats. AB - To study the involvement of testosterone in the development of spatial abilities, testosterone propionate (TP) was administered to male and female rats during the first week after birth. As adults, these rats were trained and tested on the radial arm maze (RAM) or the Morris water maze (MWM). Sex and neonatal TP treatment influenced number of trials to criterion, accuracy, and the use of an adjacent-arm strategy on the RAM, as well as the speed with which the rats learned the location of a hidden platform in the MWM. On both RAM and MWM, control males performed better than control females, but TP treatment reversed this pattern, producing better maze performance in females and worse in males. Neonatal TP effects on MWM performance were also examined in 21-day-old male and female rats. Performance paralleled that of the adults in all but the testosterone-treated male group, which did not differ from control males. The results of this study provide support for the hypothesis that circulating testosterone during brain development may play a role in the development of spatial memory, and suggest that, in the rat, both the sex difference and testosterone influence are present early in life. PMID- 8466655 TI - Three independent factors characterize spontaneous rat motor activity. AB - A scaling approach was introduced recently to assess sequential and geometrical aspects of animal behavior. This study describes the relationship between different measures of unconditioned motor activity of rats. Specifically, the amount of motor activity was assessed using both a traditional photobeam break measure, counts, and the temporal scaling exponent, alpha, which describes the ratio of fast to slow behavioral micro-events. The sequential characteristics of the behavior were assessed by the dynamical entropy, h, describing the degree of unpredictability of future movements. The geometrical characteristics of rat motor activity were quantified by the spatial scaling exponent, d. Exploratory activity was measured by counting rearings and holepoking responses. A factor analysis of these measures was conducted based on results from 137 drug-naive animals that were tested for 1 h in the Behavioral Pattern Monitor. Three independent factors account for 77% of the variance. These factors can be described as the 'amount of activity', 'sequential response organization', and 'exploratory activity'. The factor loadings support the initial hypothesis that the geometrical structure of rat motor activity, i.e. the spatial scaling exponent d, varies independently from the amount of activity, i.e. counts. In addition, the distribution of these measures did not deviate significantly from normality suggesting that the z-scores of these variables, which have been used previously in the d-alpha plane description, are able to indicate significant changes of behavior. These results suggest that unconditioned motor activity is influenced by at least three independent factors. The independent assessment of these factors may contribute significantly to the understanding of the neural substrates involved in the organization of unconditioned behavior. PMID- 8466656 TI - Tetrahydroaminoacridine attenuates dizocilpine-induced behavioural changes. AB - The acetylcholinesterase inhibitor tetrahydroaminoacridine (THA) is known to interact with neurotransmitter systems other than the cholinergic, e.g. several studies have shown interaction of THA with the N-methyl-D-aspartate (NMDA) receptor subtype of the glutamatergic system. We therefore investigated whether behavioral changes in rats, caused by the non-competitive NMDA-antagonist dizocilpine, were altered by THA. Spontaneous locomotion was measured in an open field and learning behaviour was evaluated in a spatial learning task in the 8 arm radial maze. Hyperactivity in the open field caused by 0.08 mg/kg i.p. dizocilpine was reversed by 5 mg/kg i.p. THA. Hyperactivity caused by 0.16 mg/kg i.p. dizocilpine was reversed by two THA doses (2.5 mg/kg, 5 mg/kg i.p.). A dizocilpine-induced acquisition deficit in the 8-arm radial maze was attenuated by THA (2.5 mg/kg) on the 6th and 7th day of testing. The effects of THA are discussed with reference to a possible functional glutamate agonism. PMID- 8466657 TI - Age-dependent effects of hippocampal muscarinic receptor blockade on memory-based learning in the developing rat. AB - The effects of ventral intrahippocampal injections of atropine sulfate on patterned single alternation (PSA), a discrimination task that requires intact short-to-intermediate-term memory, were examined in the developing rat at 16-17 and 28-32 days of age. Atropine treatment disrupted simple acquisition in some 16 to 17-day-old pups by interfering with approach to the goal, but did not eliminate PSA at either 8- or 15-s intertrial intervals when approach was normal. In the older rats, atropine treatment delayed the onset and reduced the magnitude of PSA, indicating a reduced memory-based discrimination. These results provide additional support for an increasing role of muscarinic receptors in learning and memory as this system matures in the developing rat, and suggest different mechanisms for PSA at the two ages. PMID- 8466658 TI - Development of hippocampal specialisation in a food-storing bird. AB - Previous studies demonstrated that amongst food-storing passerine birds the hippocampal region (dorso-medial cortex) is enlarged relative to the rest of the telencephalon. It has been hypothesised that this hippocampal specialisation is related to the spatial memory requirements of retrieving large numbers of stored items. Here we compare the development of the hippocampus in a food-storing and a non-storing corvid, the adults of which differ in relative hippocampal volume. The volume, cell density and number of cells in the hippocampal region of nestling (5-25 days post hatching) and adult (> 320 days old) magpies Pica pica (food-storing) and jackdaws Corvus monedula (non-storing) were measured. In both species the volume of the hippocampus increases with the volume of the rest of the telencephalon during the nestling growth phase. The relative volume of the hippocampus in 5- to 25-day-old nestlings of the two species does not differ significantly. In the food-storing magpie, the relative volume of the adult hippocampus is significantly larger than that of nestlings, whilst in the jackdaw, adults and nestlings do not differ. The density of neurons declines with increasing age and this effect is more marked in jackdaws than in magpies. Neuron number did not change significantly with age, but is significantly greater in adult magpies than in adult jackdaws. These results are discussed in relation to the possibility that changes in hippocampal volume and cell number are related to the use of spatial memory in retrieving stored food. PMID- 8466659 TI - Functional comparison of neuronal properties in the primate posterior hippocampus and parahippocampus (area TF/TH) during different behavioural paradigms involving memory and selective attention. AB - Monkeys were trained on a delayed match-to-sample (DMS) task. In addition a standardized behavioural trial was performed which involved an experimenter approaching the animal in certain sequence and presenting edible or other objects ('raisin trial'). Neuronal activity of 617 units was recorded in the posterior parahippocampus (PH) and in the posterior hippocampus (H). In many cases, we compared the activity of the same neuron in different tasks. 32.7% of the 455 PH neurons and 28.5% of the 130 H cells responded during the presentation of the visual stimuli in the DMS task. These responses were only mildly influenced by the physical dimensions of the visual stimulus, but often depended on the context in which the stimuli were presented. There was no differential response to the second stimulus that clearly depended on the nature of the first stimulus. 6.2% of the PH units, but none in H, responded in relation to the reward. 4.4% of the PH neurons, but none in H, showed a mild response during the interstimulus interval. 38.1% of 215 PH neurons and 37.8% of 45 H cells responded during one or more phases of the raisin trial. These responses were not related to the physical dimensions of the sensory stimuli. 210 PH and 41 H units were investigated during the DMS task as well as during the raisin trial. 18.1% (PH) and 12.2% (H) of the units responded during the DMS task, but not during the raisin trial; 17.1% (PH) and 36.6% (H) responded vice versa. A response in both trials was found in 17.1% of the PH neurons, but in none of the H cells. There were also other PH unit types showing responses during different aspects of the DMS task and even in other control paradigms, while no such overlap was encountered in H. Our results suggest a function of H and PH in the evaluation of the behavioural significance of sensory information. It may be this aspect which leads to anterograde memory disturbances after lesion of these areas. Since representation of neuronal information was found to be more specific in H, a possible function as an 'evaluation index' is discussed. PMID- 8466660 TI - Delayed response learning to auditory stimuli is impaired in cage-reared cats. AB - Four normal and eight cage-reared cats were used. Four of the cage-reared cats were visually deprived in the first 6 months of life. The cats were trained on a three-choice delayed response task to auditory stimuli. All normal cats mastered a 1-min delay and two cats even a 6-min delay. In contrast, two cage-reared cats failed to cope even with a 5-s delay, four cats with a 15-s delay and the remaining two cats with a 1-min delay. No significant difference was found between the non-deprived and the deprived cage-reared cats. The deficits was analogous to that shown by cage-reared cats during delayed response, visual learning. Thus, cage-rearing strongly impairs delayed responding to at least two different sensory modalities. PMID- 8466661 TI - Effects of locus coeruleus lesions on vigilance and attentive behaviour in cat. AB - Previous data have suggested that in the cat, expectancy behaviour (waiting for a target to appear) and associated electrocortical, focal, synchronized activity ('mu' rhythms) are modulated by a noradrenergic system possibly originating from the locus coeruleus (LC). To test the latter hypothesis, we have examined the behavioural and ECoG changes induced after bilateral LC lesions. Our results demonstrated that destruction of the anterior 3/4th of the LC (A6 noradrenergic cell group) resulted in a considerable increase of mu rhythms and expectancy behaviour, without episodes of drowsiness that normally occur. Destruction of the posterior fourth of LC (A4 noradrenergic group) only increased the duration of slow sleep. Extending the A6 lesion to include the dorsal ascending noradrenergic bundle also increased the expectancy behaviour and mu rhythms. Finally, when the nucleus subcoeruleus was also involved, the duration of slow sleep and the frequency of paradoxical sleep episodes increased. These findings indicate that the LC exerts an inhibitory effect on structures involved in the induction and persistence of expectancy behaviour with accompanying mu rhythms. PMID- 8466662 TI - P-3-BSA, but not P-11-BSA, implants in the VTA rapidly facilitate receptivity in hamsters after progesterone priming to the VMH. AB - Recent evidence suggests that progesterone (P) may have behaviorally relevant actions on neuronal membranes in the ventral midbrain. In the present experiments, we exploited the rapid time course predicted for non-genomic actions of steroid hormones. Ovariectomized hamsters were implanted with chronic guide cannulae, one aimed above the ventromedial hypothalamus (VMH) and the other over the contralateral ventral tegmental area (VTA). The following week animals were estrogen-primed (10 micrograms estradiol benzoate) and pre-tested for sexual receptivity 2 h after a P or P conjugated to the macromolecule bovine serum albumin (P-3-BSA) containing tube was applied to the VMH. P-3-BSA binds well to neuronal membranes, but does not penetrate them because of the large size of the BSA molecule. After the pre-test, the opposite hormone-containing insert was applied to the VTA and hamsters were tested again for sexual receptivity 5 min after this implantation. The following week, the contents of the tubes were reversed. Receptivity only occurred when P was applied to the VMH and 2 h later P 3-BSA was applied to the VTA; the reverse treatment was ineffective. These data indicate that P is capable of rapidly facilitating receptivity by actions on cell membranes in the VTA if P has been applied to the hypothalamus 2 h earlier. Progesterone conjugated to BSA at carbon 11 (P-11-BSA) was ineffective compared to P-3-BSA using the same paradigm. This suggests that the mechanism which responds to P in the ventral midbrain may require the 11 region. PMID- 8466663 TI - Event-related potentials in macaque monkey during passive and attentional processing of faces in a priming paradigm. AB - Epidural event-related potentials (ERPs) were recorded in monkeys using a priming (S1-S2) paradigm. One juvenile and 2 young adult macaque monkeys (Macaca fascicularis) viewed tachistoscopically presented pairs of faces in four possible combinations: human-human, monkey-monkey, monkey-human, human-monkey. Faces were presented upright to untrained subjects. Subsequently, one adult monkey was trained to associate the occurrence of a monkey-monkey pair of faces with juice reward. In a separate control experiment, the same stimuli were presented upside down. In both the upright and inverted conditions, adult monkey ERPs exhibited a P1-N1-P2 complex of peaks in the 400 ms following stimulus presentation. However, only upright faces elicited a prominent, widely distributed negativity (N4) in the 400-800 ms interval and a long-duration negativity (LDN) in the last 400 ms of the 1,400-ms epoch. N4 was earlier in latency, larger in amplitude, and larger over left hemisphere in response to monkey faces compared to human faces. It was also sensitive to the preceding or priming stimulus, exhibiting larger amplitudes when S1 matched S2 than when it did not. Trained monkey waveforms differed from untrained monkey responses in terms of the appearance of an N2-P3 complex. P3 was bilaterally symmetrical, larger in magnitude, and delayed in latency in response to monkey faces. The differences in components in the two conditions suggest that monkey ERPs can distinguish between passive and attentional processing of faces. N4 appears to reflect the recognition of conspecifics, is sensitive to priming, and occurs primarily over left hemisphere. Rewarded presentation of faces results in P3-like components that may reflect the novelty, meaningfulness, or active nature of the response. The differences in distribution between P3 and N4 suggest that they do not share the same neural sources. PMID- 8466664 TI - Recovery of a temporally based visual discrimination after visual cortex lesion in the rat. AB - In Expt. 1, rats were conditioned to emit a shock avoidance response when the pulse rate of a light was increased. Then, after bilateral visual cortex lesions, the rats were given 10, 20, or 40 days recovery before relearning the discrimination. While all rats were able to relearn the discrimination response, lesion rats had a performance deficit after all recovery periods. Expt. 2 compared the effects of postoperative visual pulse rate training to those of auditory pulse rate training on relearning of the photic pulse-rate discrimination 10 days after visual decortication. Recovery of discrimination responding was better after auditory pulse rate training than after visual training. These data suggest that visual cortex lesions in the rat disrupt perceptual or associational functions involving the temporal features of a visual stimulus. In addition, generalization of relational properties during cross-modal training through multimodal CNS structures appears to enhance recovery of behavior after brain insult. PMID- 8466665 TI - Stopping behavior: constraints on exploration in rats (Rattus norvegicus). AB - In the absence of an obvious reference place, rat locomotor behavior in a novel environment appears haphazard. In previous work, one or two places termed home bases, were shown to stand out from all the other places in the environment in terms of the behaviors performed in them and in terms of their behavioral stability. We use home base location as a reference place for rat movement in locale space, by defining an excursion as a trip starting at a home base and ending at the next stop at a home base. We then establish the uniform distribution as an appropriate model for the number of stops per excursion. This way we show that there is an intrinsic upper bound on the number of times a rat stops during an excursion. As a rat leaves the home base, home base attraction increases with every additional stop performed by it, first slowly and then fast. This cumulative process of attraction may be concluded after each stop, as long as the number of stops does not exceed an intrinsic upper bound; once the upper bound is reached, the rat concludes that excursion and returns to base. The session's upper bound does not increase with the size of the explored area. PMID- 8466666 TI - The predictive value for performance speed of preparatory changes in neuronal activity of the monkey motor and premotor cortex. AB - Three monkeys were trained in a precued reaction time (RT) paradigm. An initial preparatory signal (PS) provided complete, partial or no information about direction and extent of a wrist flexion/extension movement which was executed after the second, response signal (RS). A PS providing information about direction shortened the RT much more than a PS indicating movement extent. The activity of 464 task-related neurons was recorded in the primary motor (MI) and premotor (PM) cortex. Not only the timing and amplitude of mean activity changes were analyzed, but also trial-by-trial correlation analyses between RT and discharge frequency during the PS-RS interval were conducted. Correlations were stronger in the condition of information about direction than in conditions of information about extent or no information. Considering directionally selective neurons, correlations were stronger when the neuron's preferred direction than the opposite direction was precued. Correlation distributions were similar for MI and PM. Correlations were negative when preparatory activity increased during the PS-RS interval, and positive when activity decreased. Correlation analyses between behavioral performance and neuronal activity can thus be considered as a powerful tool to obtain a deeper insight into the functional mechanism of motor preparation. PMID- 8466667 TI - The effects of V4 lesions on the visual abilities of macaques: hue discrimination and colour constancy. AB - Monkeys with lesions of cortical visual area V4 were compared with unoperated monkeys in three experiments. In Expt. 1 they were tested for the reacquisition of a pre-operatively learned hue discrimination task. In Expt. 2, as a test of colour constancy, the monkeys were required to perform previously overlearned colour discrimination tasks when the amounts of red, green and blue light in the illuminant were changed. In Expt. 3 the animals were compared on the post operative acquisition of hue, greyness and saturation discrimination tasks. The results of Expt. 1 showed that monkeys with V4 lesions can regain their pre operative levels of performance on hue discrimination tasks. Expt. 2 showed that monkeys with V4 lesions have a colour constancy deficit. Expt. 3 reinforced the finding that the animals with V4 lesions could learn to perform fine hue discriminations but that their final, asymptotic performance was not as reliable as that of normal animals. The wavelength discrimination data are discussed within the context of recent electrophysiological findings that V4 is involved in selective attention to visual stimuli and the constancy data are interpreted as evidence that V4 is important for defining colour constancy thresholds but not for constructing the perceptual categories underlying constant colour perception. PMID- 8466668 TI - Regional distribution of functions in dorsolateral prefrontal cortex of the the monkey. AB - Single-cell responses were obtained from 352 neurons in dorsolateral prefrontal cortex (Walker's areas 9 and 46) of three monkeys. The neurons were classified functionally according to their responsiveness to visual, auditory and somatosensory stimulation, and to correlation of their activity with spontaneous eye or limb movements. A comparison between the distribution of different functions and known modality-specific anatomical connections to various sectors of this area showed a good correspondence. On average somatosensory and motor neurons were located more ventrally than the remaining ones, and were concentrated to the middle third of the inferior bank of principal sulcus and adjacent inferior convexity, where a number of somatosensory projections overlap. Oculomotor neurons were found caudally in both banks of principal sulcus and in a narrow band on the dorsal convexity, coinciding with the projection fields of areas 7a and 7ip of posterior parietal cortex, superior colliculus, and paramedian pontine tegmentum. Other functions were scatteredly distributed. Visual neurons which preferred moving to stationary stimuli were located more caudally and dorsally than other visual neurons. The present study shows that a parcellation of dorsolateral prefrontal cortex proposed on the basis of anatomical connectivity is also functionally evident. PMID- 8466669 TI - Lesions of the frontal eye field impair pursuit eye movements, but preserve the predictions driving them. AB - Visually guided eye movements are driven by a mix of current signals (e.g. visual motion) and prior experience (predictive strategies). Previously, large ablations of the frontal eye field (FEF) impaired visually guided smooth pursuit. This study examined if the pursuit decrement could be laid to a selective loss in predictive signals. Normal monkeys demonstrated some of the same predictive eye movements documented in humans. They pursued periodic visual targets with near zero phase lag. When such targets suddenly disappeared, the monkeys continued smooth pursuit without visual guidance for several reaction times. These epochs of 'blind pursuit' achieved a peak velocity proportional to the prior target frequency just experienced by the monkey. With predictable step-ramp targets smooth eye movements sometimes preceded target motion (anticipatory pursuit). Reaction time to begin pursuit was influenced by the target velocity of prior trials. Small unilateral ablations of 'low threshold' FEF showed smooth pursuit if the fundus of the arcuate sulcus was thoroughly removed. On the step-ramp targets the slowing was evident in both the initial 100 ms and subsequent portions of pursuit. During sine pursuit blind epochs were more slowed by surgery than were visually guided epochs of pursuit. Ipsilateral anticipatory pursuit was abolished in one subject, but not in the other subject with pursuit deficits. Otherwise, pursuit after surgery continued to display the influence of predictive strategies. The average phase lag of periodic pursuit remained much less than the pursuit system's reaction time. Blind epochs persisted after the periodic target disappeared, albeit with a lower peak velocity. Reaction time to begin pursuit of step-ramp targets remained a function of the monkey's experience on prior trials. It is argued that the FEF pursuit deficits do not reflect the loss of visual motion signals or the loss of some 'cognitive' signal such as a prediction about the target's motion, but rather can be explained as a motor deficit. PMID- 8466670 TI - Statistical mechanical approach for predicting the transition to non-B DNA structures in supercoiled DNA. AB - Supercoiling causes global twist of DNA structure and the supercoiled state has wide influence on conformational transition. A statistical mechanical approach was made for prediction of the transition probability to non-B DNA structures under torsional stress. A conditional partition function was defined as the sum over all possible states of the DNA sequence with basepair 1 and basepair n being in B-form helix and a recurrence formula was developed which expressed the partition function for basepair n with those for less number of pairs. This new definition permits a quick enumeration of every configuration of secondary structures. Energetic parameters of all conformations concerned, involving B form, interior loop, cruciform and Z-form, were included in the equation. The probability of transition to each non-B conformation could be derived from these conditional partition functions. For treatment of effects of superhelicity, supercoiling energy was considered, and a twist of each conformation was determined to minimize the supercoiling energy. As the twist itself affects the transition probability, the whole scheme of equations was solved by renormalization technique. The present method permits a simultaneous treatment of several types of conformations under a common torsional stress. A set of energetic parameters of DNA secondary structures has been chosen for calculation. Some DNA sequences were submitted to the calculation, and all the sequences that we submitted gave stable convergence. Some of them have been investigated the critical supercoil density for the transition to non-B DNA structures. Even though the reliability of the set of parameters was not enough, the prediction of secondary structure transition showed good agreement with reported observation. Hence, the present algorithm can estimate the probability of local conformational change of DNA under a given supercoil density, and also be employed to predict some specific sequences in which conformational change is sensitive to superhelicity. PMID- 8466671 TI - An elastic model for in-plane deformations of small DNA rings. AB - In-plane deformations of an elastic ring are analyzed as a model for structural distortions of small covalently-closed DNA rings with little or no writhe. The static conformation of an unconstrained elastic ring is a geometric circle, but thermal fluctuations away from the circle are found to be significant. An elastic ring confined in a cylindrical pore of rigid radius less than the radius of the free ring is studied as a model for a small DNA ring in a tight resolving gel. The model is extended to include deformability of the pore. Larger rings are relatively more deformed in the pore than smaller ones. This result may be pertinent to the observation that at constant linking number the mobility of small DNA rings in a resolving gel decreases as the number of base pairs increases. PMID- 8466672 TI - Binding site for ethidium cation in the major groove of B-form DNA. AB - Molecular modeling of the system composed of ethidium cation initially intercalated through the major and minor grooves of the B-DNA form of 5'GCATGC3' into the central AT pairs, with the phenyl group oriented either toward or away from the helical axis, led upon energy minimization to intercalation complexes only when the phenyl group was initially oriented away from the helical axis. For the other two cases, energy minimization led to extrusion of the ethidium from the helix to form unanticipated outside-bound complexes stabilized by specific hydrogen bonds. It is suggested that outside-bound major groove complexes involving the GXXXG sequence may play important roles in the reaction mechanism of ethidium intercalation and in its action as a drug. PMID- 8466673 TI - Conformational isomerizations of poly(dA-dT) are dramatically influenced by a substitution of a minor amount of adenine by purine or amino2purine. AB - We have synthesized poly(dA,dPu-dT) and poly(dA,n2dPu-dT) containing, respectively, 5.7% of purine and 7.4% of amino2purine in place of adenine to demonstrate that these apparently negligible perturbations of the primary structure have dramatic consequences for the polynucleotide conformational isomerizations. The replacement of adenine by amino2purine, preserving the number of hydrogen bonds between the complementary bases, has a stronger effect on the polynucleotide conformational isomerizations than the replacement with purine that is bound only by a single hydrogen bond to thymine. Nevertheless, poly(dA,dPu-dT) forms a more thermostable duplex than poly(dA,n2dPu-dT). Furthermore the few amino2purines in poly(dA,n2dPu-dT) inhibit its isomerization into X-DNA, stabilize but modify A-DNA and stabilize Z-DNA. Kinetics of the B-Z transition of poly(dA,n2dPu-dT) is fast to indicate that the amino groups in the double helix minor groove substantially decrease the kinetic barrier between B- and Z-DNA. On the other hand, the replacement of adenine by purine destabilizes both Z-DNA and A-DNA, and the destabilization of X-DNA is weaker than with amino2purine. A-form and B-form perhaps coexist in poly(dA,dPu-dT) at high concentrations of ethanol. PMID- 8466674 TI - Investigation of solution structure of d(GAATTTAAATTC)2 by 1H NMR, molecular dynamics, mechanics, refinement by back-calculation of the NOESY spectrum and analysis of this structure using X-ray data. AB - 1H NMR spectroscopy, restrained molecular mechanics and dynamics and refinements after back-calculation of the NOESY spectrum have been performed to study the structure of the d(GAATTTAAATTC)2 duplex and to determine whether it is bent or not. It is found that the duplex adopts a B-type conformation; all sugar conformations belong to the C2' endo region and purines have a larger pseudorotation angle as compared to pyrimidines. The cross-strand AH2(n)-AH1' (m + 1) distance (where (n) and (m) are complementary residues), crucial for an anomalous A/T tract structure, is large on the TA step and gradually decreases at the 3' and 5' ends of the TTTAAA tract and follows the rules proposed previously [Chuprina, V.P., Lipanov, A.A., Fedoroff, O.Yu, Kim, S.G., Kintanar, A., and Reid, B.R., Proc. Natl. Acad. Sci. U.S.A. 88, 9087 (1991)]. The changes in this distance correlate with those in the T1 value for AH2 protons which we measured for several oligonucleotide sequences. A total number of about 250 interproton distance constraints were determined from NOESY spectra and were used for structure determination by molecular mechanics, dynamics and refinement by back calculations. It is shown that these data are not enough to determine whether the duplex is bent or not. The whole family of B-type conformations including bent and straight structures fit well with the available NMR data. In principle, additional non-NMR data could be used in order to reduce the number of the allowable structures. The refinement of the structures with additional different non-NMR constraints (used as a driving force) on P-P or H1'-H1' minor groove width distances in the TA region shows a very good correlation between these distances and the angle of bending of the dodecamer. The more the minor groove width increases in the TA region the more the duplex is bent at the major groove of this region. On the other hand, there is also a very good correlation between P-P, H1'-H1' and AH2-H1' cross-strand distances as follows from analysis of X-ray B-type structures. These two correlations, together with the increased AH2-H1' cross-strand NMR distance in the TA region of the dodecamer indicate that the duplex should be characterized by a wider minor groove in the TA region and be bent in the major groove in this region. PMID- 8466675 TI - Quantum chemical and molecular mechanics studies on the binding of stereoisomers of the oligopeptide antibiotics amidinomycin and noformycin to the minor groove of B-DNA. AB - Ab initio calculations (Hartree-Fock) using the 6-31G basis set have been performed on two chiral oligopeptide antitumor antibiotics amidinomycin 5 and noformycin 6. The latter are DNA minor groove binding agents related to the A.T recognizing netropsin 4 and distamycin 3 but, unlike the latter, bear stereocenters (two for 5 and one for 6) that may be expected to affect binding to the B-DNA receptor. Geometry optimized conformations, energies and distribution of electrostatic charges within the molecules were derived. The rotational barrier for bond C3-C6 in 6 was calculated to be ca. 6 kcal.mole-1 and the dipole moment for 6 was 7.69D and for 5 was 5.58D. The ab initio derived parameters of the geometry optimized conformations of the different possible stereoisomeric forms of 5 and 6 were used to interpret their different interactions with the minor groove of DNA at both A.T and G.C sequences and the results were compared with molecular mechanics calculations. The order of binding of the four stereoisomers of 5 at the preferred (A.T)n sequences by both ab initio and molecular mechanics calculations is 1S,3R > RR > RS > SS. The predicted energy differences for complexation with DNA of the other stereoisomers from that of 1S,3R are: RR (4.2%); RS (6.7%) and SS (21.5%). In the case of noformycin the 4R structure binds more effectively than the enantiomer. Considerations of phasing in the computed distances between hydrogen bond donating sites in the DNA-bound antibiotics provide further insight into the binding processes. In the complexes of noformycin 6 the N-N1-N4 and N1-N5 distances (9.05 and 9.15 A respectively for 4R-6 and 9.23 and 9.26 A respectively for 4S-6) are close to the optimum value of 9.1 A for effective binding. In the case of amidinomycin 5 the best agreement with the optimum value occurs with the strongest binding diastereomer 1S,3R (N1 N3 = 8.91, N1-N4 = 9.41 A). The unexpected result, consistent in both ab initio and molecular mechanics treatments, is that, in contrast to the cases of kikumycin 1 and anthelvencin 2, the natural 3S configuration of 5 and 4S of 6 do not confer maximal binding efficiency. This suggests that biogenetic factors in the generation of the oligopeptide antibiotics lead to maximum DNA binding in the cases of kikumycin and anthelvencin but not in the cases of amidinomycin and noformycin. PMID- 8466676 TI - Stereochemistry of 2'-5' linked nucleic acids: crystal and molecular structure of ammonium adenylyl-2',5'-adenosine tetrahydrate: a core fragment of 2'-5' oligo A's produced by interferon induced adenylate synthetase. AB - The preponderance of 3'-5' phosphodiester links in nucleic acids is well known. Albeit less prevalent, the 2'-5' links are specifically utilised in the formation of 'lariat' in group II introns and in the msDNA-RNA junction in myxobacterium. As a sequel to our earlier study on cytidylyl-2',5'-adenosine we have now obtained the crystal structure of adenylyl-2',5'-adenosine (A2'p5'A) at atomic resolution. This dinucleoside monophosphate crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 7.956(3) A, b = 12.212(3) A and c = 36.654(3) A. CuK alpha intensity data were collected on a diffractometer. The structure was sloved by direct methods and refined by full matrix least squares methods to R = 10.8%. The 2' terminal adenine is in the commonly observed anti (chi 2 = 161 degrees) conformation and the 5' terminal base has a syn (chi 1 = 55 degrees) conformation more often seen in purine nucleotides. A noteworthy feature of A2'p5'A is the intranucleotide hydrogen bond between N3 and O5' atoms of the 5' adenine base. The two furanose rings in A2'p5'A show different conformations - C2' endo, C3' endo puckering for the 5' and 2' ends respectively. In this structure too there is a stacking of the purine base on the ribose O4' just as in other 2'-5' dinucleoside structures, a feature characteristically seen in the left handed Z DNA. In having syn, anti conformation about the glycosyl bonds, C2' endo, C3' endo mixed sugar puckering and N3-O5' intramolecular hydrogen bond A2'p5'A resembles its 3'-5' analogue and several other 2'-5' dinucleoside monophosphate structures solved so far. Striking similarities between the 2'-5' dinucleoside monophosphate structures suggest that the conformation of the 5'-end nucleoside dictates the conformation of the 2' end nucleoside. Also, the 2'-5' dimers do not favour formation of miniature classical double helical structures like the 3'-5' dimers. It is conceivable, 2-5(A) could be using the stereochemical features of A2'p5'A which accounts for its higher activity. PMID- 8466677 TI - Characterization of gamma-radiation induced decomposition products of thymidine containing dinucleoside monophosphates by nuclear magnetic resonance spectroscopy. AB - To study the chemical and biochemical influence of loss of base aromaticity, dinucleoside monophosphates containing cis-5R,6S-thymidine glycol (Tg) and 5R and 5S 5,6-dihydrothymidine (Th) were prepared from d-ApT and d-TpA by KMnO4 oxidation and rhodium-catalysed hydrogenation, respectively. One and two dimensional 1H NMR techniques were used to characterize the solution conformation of each of the modified dinucleoside monophosphates for comparison with the unmodified compounds. Coupling constant data show that all sugar moieties adopt a predominantly 2'-endo conformation. Estimates of proton-proton distances from two dimensional NOE experiments reveal that most of the glycosidic bonds prefer the anti conformation. Analysis of the C5'-C4' (gamma) torsion angle of the hydroxymethyl group using 3JH4'H5' and 3JH4'H5" data indicate that these modifications to thymine have little effect on the gamma conformer populations. Although, in general, additions at C5 and C6 of thymine in d-ApT and d-TpA profoundly distort the pyrimidine, they do not otherwise significantly alter the conformation of these compounds relative to the unsubstituted dinucleoside monophosphates. The one exception is the thymine glycol of d-TgpA, which appears to have a higher syn population than the parent compound. PMID- 8466678 TI - Mutations induced by 1-nitrosopyrene and related compounds during DNA replication in human cells and induction of homologous recombination by these compounds. AB - The transformation of normal human cells into cancer cells is a multistep process. Evidence suggests that a minimum of five independent steps (changes) are required for the development of certain kinds of human cancer, as well as for malignant transformation of human cells in culture. Mutations are one of the mechanisms involved in bringing about such changes. A single DNA base substitution mutation can activate an oncogene or inactivate a tumor suppressor gene. Because the action of tumor suppressor genes is to prevent cells from becoming malignant, the activity of both copies of such genes must be eliminated before suppression is lifted. Homologous mitotic recombination between a mutant tumor suppressor gene allele and its non-mutant allele is one mechanism for accomplishing this. The present study was designed to investigate the mechanisms by which certain carcinogenic compounds found in diesel exhaust particles and structurally-related N-substituted aryl carcinogens induce such base substitution mutations and homologous recombination events in mammalian cells in culture, including human cells. The system we employed to determine rapidly the kinds of mutations induced by these compounds, as well as the location of the point mutations in the target gene, involved a circular DNA molecule (plasmid) carrying a small target gene, supF. The target gene was exposed in vitro to radiolabeled compounds and then was allowed to replicate in human cells where the mutations were formed. The sites of mutation induction were compared with the sites of stable binding of the carcinogens to the DNA (adducts). The system used to determine whether these agents could induce homologous recombination consisted of a thymidine kinase-deficient mouse L cell line with a recombination substrate stably integrated into the genome. To determine whether or not excision repair was involved in the mechanism by which carcinogens induced recombination, the recombination substrate was introduced into an excision repair-proficient human cell line and two repair-deficient human cell lines. These cell lines were then compared for the frequency of recombination induced by the agents. All four N substituted aryl compounds tested in the supF mutagenesis assay produced mainly base substitutions involving guanosine-cytosine (G.C)* base pairs, primarily G.C- >thymidine-adenine (T.A) transversions. However, 1,6-dinitropyrene adducts, formed by exposing the plasmids to 1-nitro-6-nitrosopyrene in the presence of a reducing agent, also induced a significant proportion (17%) of single G.C base pair deletions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8466679 TI - The safety of Bacille Calmette-Guerin vaccination in HIV infection and AIDS. PMID- 8466680 TI - HIV wasting syndrome in the United States. AB - OBJECTIVE: To describe the characteristics of individuals > or = 13 years of age with HIV wasting syndrome in the United States and US territories. DESIGN: Retrospective review of national AIDS case surveillance data. METHODS: Data for the 147,225 individuals with AIDS reported to the Centers for Disease Control from 1 September 1987 to 31 August 1991 were reviewed. The frequency of HIV wasting syndrome and its association with demographic and exposure category variables and with other AIDS-indicator diseases were assessed. RESULTS: A total of 10,525 (7.1%) had wasting syndrome as the only AIDS-indicator condition, and 15,726 (10.7%) had wasting syndrome plus at least one other AIDS-indicator condition. Patients with wasting syndrome as the only AIDS diagnosis were more likely to be female, to be black or Hispanic, and to have a mode of HIV exposure reported as injecting drug use, heterosexual contact, or transfusion/hemophilia. The proportion of AIDS patients reported with wasting syndrome varied by geographic distribution, ranging from 11% in the northeastern United States to 47% in Puerto Rico. The association between HIV wasting syndrome and Hispanic ethnicity was due to the much higher prevalence of wasting syndrome reported in Puerto Rican AIDS patients. The other AIDS-indicator conditions most strongly associated with wasting syndrome were isosporiasis, pulmonary candidiasis, esophageal candidiasis, HIV encephalopathy, chronic mucocutaneous herpes simplex, and coccidioidomycosis. CONCLUSIONS: The association between HIV wasting syndrome and injecting drug use, and the significant racial/ethnic and geographic differences in prevalence of this AIDS diagnosis may reflect differences in diagnostic and reporting practices and/or access to medical care. PMID- 8466681 TI - Clinical correlates of in vitro HIV-1 resistance ot zidovudine. Results of the Multicentre Canadian AZT Trial. AB - OBJECTIVE: To describe the rate of development of in vitro HIV resistance to zidovudine (ZDV) and its prognostic implications within the Multicentre Canadian AZT Trial (MCAT). METHODS: HIV-infected subjects in Centers for Disease Control (CDC) stages IIB, III and IVC-2 with CD4 cell counts > 270 x 10(6)/l were treated with ZDV as part of a dose-range study. Participating volunteers underwent prospective clinical and laboratory evaluations at regular intervals. Viral cultures and sensitivity testing were performed every 12 weeks in a predefined subset of 50 volunteers. An isolate was designated ZDV-resistant if it had a median inhibitory concentration (IC50) for ZDV at least 50-fold higher than that of virus isolated from the same subject before initiation of antiviral chemotherapy. The relationship between resistance and subsequent disease progression was studied using the Mantel and Byar method, for which, at each instance of disease progression, 2 x 2 tables classifying progression versus resistance status were constructed. The observed number of progressions was compared with that expected under the null hypothesis using Mantel-Haenszel methods adjusted for baseline CD4:CD8 ratio. RESULTS: The Kaplan-Meier estimate for the cumulative development of in vitro resistance was 64% [95% confidence interval (CI), 41-78] at 180 weeks. Baseline CD4:CD8 ratio was negatively associated (P = 0.10) with the subsequent development of resistance (proportional hazard, 0.44; 95% CI, 0.17-1.10). After adjusting for baseline CD4:CD8 ratio, the numbers of observed and expected progressions following the development of resistance were 15 and 7.6, respectively (P = 0.008). A similar relative risk of progression between resistant and non-resistant states was found in the two CD4:CD8 strata; observed and expected progressions were 4 and 2.3 and 11 and 5.2 in the high and low CD4:CD8 strata, respectively. CONCLUSIONS: In vitro resistance to ZDV developed in 64% of subjects after 180 weeks of ZDV therapy. Lower CD4:CD8 ratio at baseline was associated with faster development of resistance. In addition, the development of resistance was found to be a marker of subsequent disease progression. This association persisted after adjustment for baseline CD4:CD8 ratio. Whether in vitro resistance to ZDV is merely a surrogate marker or a determinant of disease progression remains to be established. PMID- 8466682 TI - Comparison of two dose regimens of zidovudine in an open, randomized, multicentre study for severe HIV-related thrombocytopenia. AB - OBJECTIVE: To compare the effect of two dose regimens of zidovudine in the treatment of severe HIV-related thrombocytopenia (TP). DESIGN: Eighty-four patients with severe HIV-related TP and platelet counts < 50 x 10(9)/l were enrolled in an open study at six centres. Patients were randomized into two groups to receive zidovudine (group A, 500 mg per day; group B, 1000 mg per day) for 6 months. METHODS: Platelet counts were determined monthly and patients categorized as complete responders (CR; platelets > 100 x 10(9)/l), partial responders (PR; platelets > 50 to < 100 x 10(9)/l), or failures (F; platelets to < 50 x 10(9)/l). CD4+ and CD8+ lymphocytes, HIV antigenaemia, beta 2 microglobulin, white blood cells, mean cell volume and haemoglobin were also determined. RESULTS: Seventy-one patients (35 and 36 in groups A and B, respectively) completed the study; 11.4% of group A patients were CR and 45.7% PR; 38.9% of group B were CR and 33.3% PR. Increase in mean platelet counts was dose-related, more rapid in the higher dose group and remained significantly higher after 6 months of treatment (56.4 x 10(9)/l in group A versus 98.2 x 10(9)/l in group B; P < 0.01). CONCLUSIONS: The results confirm the efficacy of zidovudine in the treatment of severe HIV-related TP. The average for CR and PR in the two groups was 64.8%; the higher dose of zidovudine was more effective at increasing platelet counts. PMID- 8466683 TI - Intestinal parasites and HIV infection in Tanzanian children with chronic diarrhea. AB - OBJECTIVE: To determine whether specific intestinal parasites are associated with HIV infection in Tanzanian children with chronic diarrhea. DESIGN: A prospective, cross-sectional study. SETTING: Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. SUBJECTS: All children aged 15 months to 5 years admitted with chronic diarrhea, and age-matched controls. METHODS: Standardized history, physical examination, HIV serology, and stool parasitology were evaluated for all subjects. We compared three groups: HIV-infected and non-HIV infected children with chronic diarrhea and controls without diarrhea. MAIN OUTCOME MEASURES: Fecal parasites and nutritional status. RESULTS: Chronic diarrhea accounted for one-quarter of all cases of diarrheal disease in the defined age range, and children with chronic diarrhea were severely malnourished. Forty per cent of subjects with chronic diarrhea were HIV-seropositive. Although intestinal parasites were detected in approximately 50% of all three groups, diarrheagenic parasites were detected in up to 40% of children with chronic diarrhea. Blastocystis hominis was detected only in HIV-infected patients. CONCLUSIONS: HIV infection was common in children with chronic diarrhea, and parasitic agents of diarrhea may be important in children with chronic diarrhea both with and without HIV infection in this setting. B. hominis was more frequent in HIV-infected children. The immunocompromising effects of severe malnutrition may have diminished the difference between HIV-infected and non-HIV-infected children. PMID- 8466684 TI - Elevated plasma levels of vasoactive intestinal peptide in AIDS patients with refractory idiopathic diarrhoea. Effects of treatment with octreotide. AB - OBJECTIVE: To evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide. PATIENTS: Three AIDS patients were evaluated for severe watery diarrhoea of 2-6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities. They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment. METHODS: A complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed. Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects. RESULTS: Since no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed. Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5 pmol/l (values < 8.8 pmol/l in the control group). One patient received 50-100 micrograms octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values. CONCLUSIONS: Although the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects. Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment. PMID- 8466685 TI - Diagnosis of visceral leishmaniasis in HIV-infected individuals using peripheral blood smears. AB - OBJECTIVE: To compare the clinical and laboratory features of visceral leishmaniasis (kala-azar) in HIV-infected and non-infected subjects, and to determine the presence of Leishmania amastigotes in circulating leukocytes using peripheral blood smears. PATIENTS: Twenty-eight HIV-infected and six HIV-negative adult patients diagnosed as having kala-azar presenting at one institution over a 7-year period. METHODS: Retrospective review of clinical charts and re examination of peripheral blood smears. RESULTS: There were no significant differences in the clinical presentation and laboratory features of HIV-positive and HIV-negative patients. However, Leishmania amastigotes were observed in circulating leukocytes in eight out of the 17 available peripheral blood smears (15 from HIV-infected patients). All eight individuals presenting with Leishmania in peripheral blood leukocytes were HIV-positive. CONCLUSIONS: Direct visualization of Leishmania amastigotes in leukocytes on peripheral blood smears enabled the diagnosis of kala-azar in a high proportion [eight out of 15 (53%)] of our HIV-infected patients. PMID- 8466686 TI - The treatment-free incubation period of AIDS in a cohort of homosexual men. AB - OBJECTIVE: The treatment-free incubation period distribution was estimated from data obtained from a cohort of homo/bisexual men in Amsterdam. DESIGN: Participants in a cohort study that started in Amsterdam at the end of 1984 were seen at 3- or 6-monthly intervals. The analysis excluded time since the start of zidovudine treatment (given to 27 individuals) and no cohort member received primary Pneumocystis carinii pneumonia prophylaxis (i.e., before AIDS diagnosis) before February 1990. METHODS: Both HIV-positive (n = 269) and HIV-seroconverted (n = 79) homosexual men were included in this study. Of these, 68 developed AIDS before February 1990. The unobserved dates of seroconversion were obtained by multiple imputation. The incubation period distribution was estimated from these data by direct Kaplan-Meier analysis and by using parametric Weibull and gamma distributions (including a parameter describing the probability of never progressing to AIDS). Our results are compared with published estimates of progression to AIDS from other homo/bisexual cohort studies. RESULTS: Both the Weibull and the gamma distributions provide equally good empirical descriptions of the incubation period distribution for up to 7 years postseroconversion, but the estimated gamma distribution (median, 9.2; mean, 10.2; percentage AIDS at 7 years, 33%) should be preferred beyond that time, due to a slowing of the hazard rate. There is insufficient information to be able to estimate accurately the probability of never progressing to AIDS. CONCLUSIONS: The time-dependent pattern of HIV incidence should be considered in the analysis of prevalent cohort studies. Our results are in agreement with other homo/bisexual cohort studies, and will be valuable for future comparison with and understanding of the epidemiological consequences of clinical treatment that delays the onset of AIDS. PMID- 8466687 TI - Three-year neuropsychological follow-up in a selected group of HIV-infected homosexual/bisexual men. AB - OBJECTIVE: To evaluate changes in cognition in a selected group of asymptomatic homosexual/bisexual men over a 3-year period. PATIENTS AND METHODS: Sixty HIV infected (Centers for Disease Control stage II) subjects and 60 controls (individually matched for age and years in education) were administered neuropsychological tests evaluating attention, language, memory, logic and visuo motor abilities. None of the patients had a history of alcohol or drug abuse, and all received the baseline cognitive evaluation within 18-24 months of seroconversion. RESULTS: The HIV-infected subjects differed from controls in only one of the six memory tests (P < 0.01). Follow-up evaluation after 18 and 36 months (available for 51 and 36 subjects, respectively) demonstrated a significant deterioration in visuo-motor ability (P < 0.01) only in subjects who had progressed to AIDS, without signs or symptoms of central nervous system involvement. CONCLUSIONS: The data suggest that cognitive alterations in asymptomatic stages of HIV infection are in most subjects minor and do not develop. Percentage rates of CD4 lymphocyte decline appear to be significantly related to deterioration in visuo-motor abilities. PMID- 8466688 TI - Evaluation of a cognitive-behavioural intervention for HIV prevention among injecting drug users. AB - OBJECTIVE: To evaluate the effectiveness of relapse prevention (RP) and brief intervention (BI) in reducing HIV risk-taking behaviours among injecting drug users (IDU) enrolled in methadone programmes. The hypotheses tested were: (1) that a six-session RP programme would be more effective in reducing HIV risk taking behaviours than a one-session BI and a non-intervention control condition (C); and (2) that BI would be more effective in reducing HIV risk-taking behaviours than C. DESIGN: Clients of methadone programmes were randomly assigned to either RP, BI, or C. Follow-up occurred 6 months after pre-intervention assessment and was conducted by independent research assistants who were not aware of subjects' group allocations. SETTING: Confidential assessment interviews and interventions generally took place at the methadone unit treating the subject. PARTICIPANTS: Ninety-five IDU enrolled in methadone programmes. Study entry criteria were: injection of any drug in the 6 months before the day of pre intervention assessment; literacy in English; agreement to HIV-antibody testing for research purposes; and no known diagnosis of a serious mental illness. Eighty subjects were contacted successfully for a 6-month follow-up. INTERVENTIONS: The RP intervention was a six-session programme. Each 60-90 min session was conducted individually. The BI was a one-session motivational interview lasting 60-90 min, accompanied by a self-help booklet. MAIN OUTCOME MEASURES: All subjects were administered the Drug Use Scale and HIV Risk-Taking Behaviour Scale of the Opiate Treatment Index and consented to the collection of a capillary blood sample for HIV-antibody testing at pre-intervention assessment and follow-up. At follow-up, the Highest HIV Risk-Taking Behaviour Scale, collateral reports from subjects' sexual partners pertaining to the previous month and urinalysis results for the month before follow-up were collected. RESULTS: Compliance with interventions was good. Correspondence of self-reports with urinalysis and collateral reports was satisfactory. There were no significant differences between groups in risk-taking behaviours during the month before follow-up. However, there was evidence of a lower rate of needle-risk behaviour (sharing and cleaning) during the heaviest risk-taking month since pre-intervention assessment in the group given RP. There were no indications that BI was of greater benefit than the usual methadone treatment and neither intervention appeared to reduce sexual risk behaviour. CONCLUSIONS: The results are cautiously interpreted as showing that individual RP programmes decrease the level of needle-risk behaviour during relapse episodes, but further research is required to replicate this finding. PMID- 8466689 TI - Sustaining safe sex: a longitudinal study of a sample of homosexual men. AB - OBJECTIVE: TO assess the maintenance of safe sexual practice. (We use the term 'safe' sex throughout the paper, since 'safe' is the term adopted by the Australian National Committee on AIDS). DESIGN: Maintenance was assessed by comparing sexual behaviour with both regular and casual partners reported in a 1986/1987 survey (time 1) with behaviour reported in a second survey in 1991 (time 2). METHOD: The 145 homosexually active participants were a non-clinical sample recruited in 1986/1987 by advertisement and followed-up in 1991. A structured questionnaire was administered at both times. Items included questions about the nature of the men's sexual relationships and their sexual practices. RESULTS: Our findings indicate that the majority of men had sustained safe sex practices. HIV prevention strategies adopted included condom use, avoidance of anal intercourse and negotiated safety (i.e., the negotiated practice of unprotected anal intercourse within regular partnerships of concordant serostatus). CONCLUSIONS: Negotiated safety is not the same as relapse. PMID- 8466690 TI - The effectiveness of condom use in heterosexual prostitution in The Netherlands. AB - OBJECTIVES: To assess the extent to which condoms are used effectively in commercial heterosexual intercourse. Data on the number of condoms that had broken or slipped off, the sexual technique during which this had occurred and the perceived cause of failure were collected. The use of non-water-soluble lubricants and non-fortified condoms during anal intercourse, and the demand for a greater variety of condom sizes were also examined. SUBJECTS AND METHODS: One hundred and twenty-seven female prostitutes and 91 male clients from different parts of The Netherlands were interviewed face-to-face between July 1990 and March 1991. RESULTS: Of those who used condoms during vaginal intercourse, 49% of the prostitutes had experienced condom breakage in the previous 6 months, and 16% of the clients in the previous 12 months. The breakage rate was 0.8% for prostitutes and 1.5% for clients. Condom quality was seldom reported as the cause; breakage was generally attributed to human factors, such as rough or prolonged intercourse, incorrect handling of the condom or the use of insufficient lubricant. Prostitutes also identified penis size as a cause. Condoms slipping off before or after ejaculation was reported less frequently than breakage. Thirteen per cent of clients and 36% of prostitutes expressed a need for either smaller or larger condoms. Of the prostitutes, 9% used oil or vaseline as a lubricant. CONCLUSIONS: In view of the low rate of condom failure in heterosexual prostitution in The Netherlands, the potential spread of HIV by this means is small. The use of a greater variety of condom sizes may further reduce the failure rate. Few prostitutes remain ignorant about the adverse effects of oil-based lubricants on condoms. PMID- 8466691 TI - The effects of post-test counselling on condom use among prostitutes in The Gambia. AB - OBJECTIVES: To determine the effect of counselling on condom use by prostitutes. DESIGN: Cohort study. SETTING: Field-based study in The Gambia. PARTICIPANTS: Thirty-one (12 HIV-positive and 19 HIV-negative) prostitutes. INTERVENTIONS: Post test HIV counselling. MAIN OUTCOME MEASURES: Levels of condom use. RESULTS: Overall, counselling had no effect on condom use. CONCLUSIONS: Scarce resources should be directed towards providing condoms in bars rather than counselling. PMID- 8466692 TI - Estimating the seroincidence of HIV-1 in the general adult population in Kigali, Rwanda. AB - OBJECTIVE: To estimate the seroincidence of HIV-1 infection in the general adult population of Kigali, Rwanda. DESIGN: Repeated standardized cross-sectional studies. SETTING: Two urban prenatal clinics. PATIENTS: A total of 4486 consecutive pregnant women consulting in 1989 and 1990. MAIN OUTCOME MEASURES: Prevalence of HIV-1 antibodies. RESULTS: HIV seropositivity increased by 3-5% annually over this period, indicating that it has not reached a plateau in this sentinel population. The percentage infection rates, calculated using two complementary methods, were 26.2-30.7% in 1990. Extrapolating these results to the general population of Kigali, we estimate that 2300-3800 new infections in young women and 3600-6100 new infections in young men occur annually among the total population of 350,000 in Kigali. CONCLUSIONS: A new HIV infection occurred in an adult every 50-90 min, on average, in Kigali during 1989-1990, while every 6-7 h a baby with maternally acquired HIV infection was born. Our HIV surveillance system, which is based on prenatal sentinel posts, is a useful tool for monitoring the progression of the HIV epidemic in Kigali. PMID- 8466693 TI - Safer sex maintenance among gay men: are we moving in the right direction? PMID- 8466694 TI - Safer sex among gay men: what is the ultimate goal? PMID- 8466695 TI - HIV seropositivity of blood donations in Spain: a 4-year surveillance (1988 1991). The HIV Blood Donations Study Group. PMID- 8466696 TI - Concurrent partners and the results of the Uganda Rakai project. PMID- 8466697 TI - Recurrent Kawasaki disease associated with co-infection with parvovirus B19 and HIV-1. PMID- 8466698 TI - Zidovudine-responsive pure red cell aplasia as initial manifestation of HIV infection. PMID- 8466699 TI - Antibodies to natural killer cells in HIV-infected patients. PMID- 8466700 TI - Spermicides: anti-HIV activity and cytotoxicity in vitro. PMID- 8466701 TI - Survival of HIV-infected Brazilians: a model based on the World Health Organization staging system. PMID- 8466702 TI - Statistics from the World Health Organization. PMID- 8466703 TI - A comparison of two tests for the assessment of blood pressure responses to sodium. AB - In order to assess the congruity of two different methods for the characterization of blood pressure responsivity to alterations in sodium and extracellular fluid volume balance, we studied 40 normotensive and hypertensive humans. All subjects were initially studied with a protocol of rapid sodium and volume expansion induced by intravenous administration of 0.9% saline (2 L over 4 h) followed by a day of sodium and volume depletion achieved by a low (10 mmol) sodium diet and three 40 mg oral doses of furosemide. Subsequently the subjects underwent a dietary protocol consisting of 5 days of a high (> or = 200 mmol/da) sodium diet followed by 7 days of a low (< or = 15 mmol/day) sodium diet. Blood pressure measurements as well as urinary sodium, potassium, and creatinine excretion measurements were made daily in both studies. A significant (P < .01) correlation was observed between the blood pressure responses to the separate techniques in the same individual. However, not all subjects responded in a similar qualitative fashion to the two maneuvers. The discrepancy was more frequent among subjects having a salt-resistant response to the rapid protocol. The renin response to sodium and volume depletion induced by the low sodium diet and furosemide correlated significantly (P < .001) with the subsequent blood pressure response to the low sodium diet. Subjects defined as salt-sensitive differed from the salt-resistant group by more sluggish renal adaptation to dietary sodium restriction. These findings demonstrate the congruity of two different approaches for the assessment of salt responsivity of blood pressure in humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466704 TI - Nephrosclerosis in three cohorts of black and white men born 1925 to 1944, 1934 to 1953, and 1943 to 1962. AB - The prevailing levels of blood pressure among black and white men of ages 25 to 54 years were examined by two independent approaches in this study. Data on blood pressure obtained in national health surveys (National Health and Nutrition Examination Surveys, NHANES) do not show any appreciable upward or downward trend between 1960 and 1980 in men of these ages. The histologic examination of kidney samples obtained from coroner's autopsies offers an indirect way of estimating the levels of blood pressure that prevail in populations because of statistical relationships between nephrosclerosis and blood pressure. Samples of kidney tissues archived in New Orleans from 1968 to 1986 were evaluated by quantitative morphometry for the severity of the renovasculopathies that accompany high blood pressure. The outcome showed no significant secular trend among black and white men, confirming blood pressure survey findings that show no change in the hypertensive status of the population. The black-white difference in incipient signs of hypertension was seen to be well-established by ages 25 to 34 years in all cohorts of New Orleans subjects, as well as in the NHANES survey data. These result suggest that the adolescent and young adult ages are especially important in establishing the black-white difference in hypertension. PMID- 8466705 TI - Verapamil prevents the acute hypertensive response to intracerebroventricular cadmium in conscious normotensive rats. AB - Cadmium, a trace element from natural and industrial sources, may contribute to the pathogenesis of arterial hypertension. We evaluated the effect induced by acute intracerebroventricular (icv) administration of cadmium on mean blood pressure of normotensive conscious rats. Intracerebroventricular cadmium (1 to 10 micrograms) produced a dose-dependent, sustained increase in mean blood pressure. The hypertensive response to icv cadmium was significantly (P < .01) prevented by icv pretreatment with verapamil (10 to 100 micrograms). A preventive effect was exerted also by icv nifedipine (100 micrograms); however, this result was attributable, at least in part, to the antihypertensive action of the vehicle, polyethylene glycol. The hypertensive response to icv cadmium was blunted by icv administration of 10 ng clonidine, 10 micrograms vasopressin antagonist, or 10 micrograms bradykinin antagonist (P < .05), but it was not altered by icv enalaprilat (100 micrograms). These results indicate that brain calcium channels play a role in the hypertensive action induced by icv cadmium. Accumulation of cadmium in the brain caused by prolonged exposure to this heavy metal might lead to chronic arterial hypertension. PMID- 8466706 TI - Evaluation of orthostatic hypotension using power spectral analysis. AB - To evaluate the pathogenesis of orthostatic hypotension, we studied the autonomic regulation system by measuring heart rate variability during 60 degrees passive head-up tilt using power spectral analysis in 21 patients with orthostatic hypotension (mean age 62 +/- 2 years, five with histories of cerebrovascular accidents, five with Parkinsonism, five with diabetes mellitus, three with pheochromocytoma, and three with unknown causes) and 15 normal healthy subjects as a control (mean age 63 +/- 2 years). We also assessed plasma epinephrine and norepinephrine response to tilt. During tilt, control subjects showed an increase in heart rate with no change in blood pressure. Spectral analysis of heart rate variability demonstrated increases in the low frequency band (LFB, mainly sympathetic) and low frequency band/high frequency band ratio (LFB/HFB, sympatho vagal balance). All patients with orthostatic hypotension showed a significant reduction in blood pressure with an increase in heart rate. In patients with histories of cerebrovascular accidents and with Parkinsonism, LFB and the LFB/HFB ratio did not increase. However, in other patients with orthostatic hypotension, LFB and the LFB/HFB ratio increased during tilt. Norepinephrine increased in control subjects and in patients with diabetes mellitus, pheochromocytoma, and unknown causes. In contrast, patients with histories of cerebrovascular accidents and patients with Parkinsonism showed no increase in norepinephrine. Epinephrine responses paralleled those of norepinephrine, but the changes were not significant. Thus, neurological response to tilt is not uniform in patients with orthostatic hypotension. Patients with histories of cerebrovascular accidents and patients with Parkinsonism may have impaired function of central neural mechanisms controlling blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466707 TI - Effect of antihypertensive treatment on daytime and nighttime power spectral analysis of heart rate. AB - Power spectral analysis of heart rate may provide useful information about cardiac neural activity. The aim of this study was to evaluate cardiac sympathetic and parasympathetic activity, as assessed by power spectral analysis of heart rate, in hypertensive patients before and after antihypertensive treatment. In 14 hypertensive patients and in 7 normotensive subjects 24 h Holter electrocardiogram monitoring was performed under basal conditions and after 6 months of treatment with nifedipine (n = 7) or enalapril (n = 7). Sequences of 512 RR intervals were taken for the evaluation of power spectral analysis (autoregressive method); absolute and normalized power spectral density of the peak at 0.10 Hz (low frequency peak: LF) and at 0.25 Hz (high frequency peak: HF), as well as their ratio (index of sympatovagal interaction: SVI) were calculated. Under basal conditions SVI was significantly decreased from daytime to nighttime in normotensives, while no change was observed in hypertensive patients. In all hypertensive patients a reduction of SVI during nighttime in respect to basal values was observed after treatment. SVI during nighttime was significantly reduced with both nifedipine and enalapril, while SVI during daytime was slightly increased during nifedipine treatment, and significantly reduced during enalapril treatment. Systolic and diastolic arterial pressure as well as left ventricular mass index were significantly reduced with both treatments. In conclusion, long term treatment with nifedipine or enalapril seems to be able to restore an impaired daytime to nighttime SVI modulation in hypertensive patients, even considering the potential limitations of power spectral analysis of heart rate. PMID- 8466708 TI - Determinants of platelet intracellular free calcium in essential hypertension and effect of stimulation by arginine vasopressin. AB - The aim of this study was to determine platelet intracellular free calcium with respect to age, sex, race, and agonist stimulation in patients with essential hypertension compared with normotensive subjects. Intracellular free calcium was measured, using Fura-2-AM, in 42 normotensive and 52 patients with untreated essential hypertension. Of these, 22 pairs were age, sex, and race matched. The intracellular free calcium response to agonist stimulation was measured in the presence of 1 mumol/L arginine vasopressin (AVP). Intracellular calcium was significantly raised in patients with hypertension in both the matched and unmatched groups with values (means +/- SEM) in the matched group of 68.4 +/- 2.6 nmol/L for the hypertensives and 60.2 +/- 2.1 nmol/L for the normotensives (n = 22; P < or = .02) and in the unmatched group of 63.3 +/- 1.8 nmol/L (n = 52) and 57.6 +/- 1.4 nmol/L (n = 42, P < or = .02), respectively. There was no sex difference but intracellular calcium was significantly lower in black hypertensives compared with white hypertensives (P < .005). A significant correlation with blood pressure was only observed in the combined normotensive and hypertensive group (r = 0.23; P = .030). There was no significant correlation with age in any group (even when excluding the black individuals), but in the hypertensive group there was a significant correlation with serum cholesterol (r = 0.34, P = .02; n = 46).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466709 TI - Increased inositol 1,4,5-trisphosphate binding capacity in vascular smooth muscle of spontaneously hypertensive rats. AB - High intracellular levels of free calcium (Ca2+) are found in cells of hypertensive patients, and these levels have been correlated with increased blood pressure. In the present study, we characterized inositol 1,4,5-trisphosphate (InsP3) receptors in aorta and heart microsomes of Long-Evans rats. We also studied this receptor in some organs of spontaneously hypertensive rats (SHR) to clarify the role this important component of the mechanism of Ca2+ regulation has in hypertension. Microsomal fractions were prepared from aorta, heart, adrenal cortex (organs directly involved in the regulation of blood pressure), and cerebellum (control organ, not directly involved) of 14-week-old SHR and Wistar Kyoto (WKY) rats. InsP3, receptors were studied in each microsomal fraction by a radioligand binding method with [3H]InsP3. The properties of InsP3 binding sites in each tissue were consistent with those of well-characterized InsP3 receptors: 1) InsP3 binding was specific and saturable, 2) InsP3 binding increased upon pH elevation, 3) InsP3 binding was inhibited by heparin, and 4) InsP3 had a higher binding affinity than InsP4. No significant difference of binding affinity or of maximal binding capacity between WKY and SHR was observed in microsomes from heart, adrenal cortex, and cerebellum. It is interesting that InsP3 binding capacity of SHR aorta microsomes was significantly higher (1.6 fold) than that of WKY aorta microsomes. These results suggest that increased InsP3 receptor activity in vascular smooth muscle of SHR may contribute to the elevation of blood pressure. Further studies are needed to assess the significance of this observation as regards the mobilization of intracellular Ca2+. PMID- 8466710 TI - Environmental determinants of urinary kallikrein excretion. AB - Decreased urinary kallikrein excretion has been shown to be related to hypertension. Kallikrein levels also have been shown to be determined primarily by genes, with 51% of the total variance being due to a single gene. However, there exists strong spouse-spouse correlation, indicating that common environment plays a significant role. This study used 69 pairs of monozygous twins to investigate possible dietary, biochemical, and anthropometric determinants of kallikrein that could result in this high spouse correlation. Urinary sodium and potassium excretion differences were significantly related to kallikrein differences, with urinary potassium having the strongest relationship (r = 0.46, P = .0001). Urinary pH (r = 0.23, P = .03) and systolic blood pressure (r = 0.25, P = .03) differences were associated with urinary kallikrein excretion differences independently of urinary potassium. Information on nutrients was obtained from a dietary food frequency questionnaire that ascertains usual intake over the last 5 years. Kallikrein differences between monozygous twins were not explained by differences in nutrient intake as measured by this questionnaire. Therefore, urinary potassium and pH probably represent the more acute effects of recent dietary sodium and potassium intake on urinary kallikrein levels. Urinary potassium, pH, and systolic blood pressure differences explained 34% of the difference in kallikrein levels between monozygous twins. The significant difference in systolic blood pressure between twins, even after controlling for electrolyte excretion differences suggests an additional unmeasured environmental variable that is associated with decreased kallikrein excretion and elevated blood pressure. PMID- 8466711 TI - Chronic parathyroid hormone administration reverses the antihypertensive effect of calcium loading in young spontaneously hypertensive rats. AB - To investigate the role of parathyroid hormone (PTH) in the development of hypertension, the long-term administration of human PTH (hPTH) was performed in 7 week-old male spontaneously hypertensive rats maintained on a standard calcium diet (1.1% calcium) or a high calcium diet (2.8% calcium). The hPTH was infused subcutaneously at 0.9 U/h over 2 weeks using a minipump. Two weeks after minipump implantation, rat PTH (rPTH) and 1,25-dihydroxy vitamin D (1,25-D) levels were measured and the pressor response to norepinephrine (NE) was examined. Calcium loading both attenuated the development of hypertension and reduced the pressor response to norepinephrine. Chronic hPTH administration accelerated the development of hypertension and increased the pressor response to norepinephrine in rats fed a high calcium diet, but did not affect either parameter in rats fed a standard calcium diet. The serum concentrations of rat PTH and 1,25-D were significantly lower in rats fed a high calcium diet than in those fed a standard calcium diet (rat PTH: 351 +/- 16 v 430 +/- 1 pmol/L; 1,25-D: 125 +/- 19 v 206 +/ 31 pg/mL). Chronic administration of hPTH increased the serum 1,25-D concentration in rats fed a high calcium diet (186 +/- 35 pg/mL), but did not affect that of rats fed a standard calcium diet (165 +/- 16 pg/mL). It is concluded that PTH prevented the antihypertensive effect of calcium loading in young SHR, perhaps by enhancing blood pressure reactivity through causing an increase of 1,25-D. PMID- 8466712 TI - Involvement of nitric oxide in the blastogenic response deficiency in splenocytes from spontaneously hypertensive rats. AB - It has been shown that spontaneously hypertensive rats (SHR) exhibit some abnormalities in their immune system. These include a reduced delayed hypersensitivity response, a reduction in the number of rosette-forming cells and a decreased lymphocyte blastogenic response. In this study, we further investigated the blastogenic responses of splenocytes, thymocytes, and T-enriched lymphocytes from SHR. In SHR splenocytes, the blastogenic responses to concanavalin A (Con A), phytohemagglutinin (PHA), interleukin-2 (IL-2), and phorbol 12,13-dibutyrate (PDB) plus ionomycin were significantly reduced compared with those from Wistar-Kyoto rats (WKY). In SHR thymocytes and T-enriched lymphocytes, the blastogenic responses to these activators were the same as in WKY rats. The IL-2 production by SHR splenocytes was similar to that of WKY. To elucidate the possible mechanism responsible for the blastogenic defects in SHR splenocytes, the involvement of the nitric oxide (NO) synthetic pathway was studied. The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA) corrected the defect in SHR splenocytes. L-NMMA had no effect on the splenocytes, thymocytes, or macrophage-depleted splenocytes from WKY or on thymocytes or macrophage-depleted splenocytes from SHR. The removal of macrophages from SHR splenocytes also corrected the blastogenic defect in these cells. Furthermore, the NO synthesis in Con A stimulated SHR splenocyte culture medium was statistically significantly higher than that in WKY. These results suggested that overproduction of nitric oxide by SHR macrophages may be responsible for the SHR splenocyte blastogenic defect. PMID- 8466713 TI - A new approach for evaluating circadian blood pressure levels and variability from 24 h ambulatory blood pressure profiles. AB - In 24 h blood pressure monitoring the severity of arterial hypertension is generally classified on the basis of the arithmetic mean of the diastolic blood pressure between 6 AM and 10 PM. In the present study Fourier analysis was used for evaluation of circadian blood pressure level and variability. A common reference profile was calculated on the basis of a group of 50 normotensive profiles. This reference profile is characterized by the fact that the sum of the squares of the distances between the individual profiles and the reference profile is a minimum. The individual 24 h profiles of 103 patients with untreated arterial hypertension were also each described by a Fourier series and were then compared with the normotensive reference profile. The comparison was made not only with respect to the absolute pressure over 24 h but also with respect to the circadian fluctuations in blood pressure. Our results show that the Fourier analysis of 24 h blood pressure profiles presented here can be used for more precise evaluation of 24 h blood pressure profiles. PMID- 8466714 TI - Short- and long-term goals in the treatment of hypertension. Symposium proceedings. Madrid. PMID- 8466715 TI - Effects of isradipine and nifedipine retard in hypertensive patients with type II diabetes mellitus. AB - Twenty patients were randomized to receive either 2.5 mg isradipine twice daily or 20 mg nifedipine retard once daily for 6 months. After 2 weeks of placebo wash out, evaluations were carried out every 4 weeks. These evaluations included assessment of blood pressure, lipid profile, hemoglobin A1 sigma glucagon, C peptide, and insulin requirements. Both isradipine and nifedipine retard lowered systolic and diastolic blood pressures to normal values (P < .001). However, isradipine was accompanied by a decrease in heart rate (P < .005). Neither drug modified hemoglobin A1c or the glycemic profile. The endogenous insulin-secretion response decreased in both treatment groups (P < .05). In conclusion, isradipine and nifedipine retard are efficacious in the treatment of hypertension in patients with type II diabetes mellitus, and neither treatment produces modification of metabolic control. PMID- 8466716 TI - Antihypertensive efficacy, safety, and tolerability of isradipine in hypertensive patients with diabetes. AB - The aim of this study was to investigate the efficacy, tolerability, and safety of isradipine in hypertensive diabetic patients. Twenty-eight patients (14 men and 14 women), of whom 15 had type II (non-insulin-dependent) and 13 had type I (insulin-dependent) diabetes mellitus, received isradipine for 6 months. A significant reduction was observed in both systolic and diastolic blood pressures (P < .00005). There were no significant differences between the type I and type II diabetes patients; metabolic control remained stable. Moderate or slight headaches were reported by four patients. In conclusion, the overall efficacy of isradipine and its tolerability were found to be very good. PMID- 8466717 TI - Antihypertensive effect of the calcium antagonist isradipine and lipid profile. AB - The hypothesis that plasma lipids may modulate the antihypertensive effect of the calcium antagonist isradipine was tested in 85 patients who had essential hypertension. Significant linear correlations were found between the antihypertensive effect of isradipine and plasma levels of total cholesterol and high-density lipoprotein (HDL2 or HDL3) in normotriglyceridemic (n = 63), but not in hypertriglyceridemic (n = 22), patients. From this, we conclude that normal levels of plasma lipids may modulate the function of calcium channels and their interaction with calcium antagonists. PMID- 8466718 TI - Transplacental passage of isradipine in the treatment of pregnancy-induced hypertension. AB - The aim of this study was to assess the concentration of isradipine in maternal and fetal plasma, and in amniotic fluid under steady-state conditions. Eight women were treated with 5-mg isradipine tablets twice daily and eight women were given slow-release isradipine capsules (SRO) twice daily for hypertension in pregnancy. Blood and amniotic fluid sampling for analysis of drug concentration was performed at delivery. In the isradipine tablet group, maternal and fetal plasma levels were 788 +/- 701 pg/mL (mean +/- SD) and 270 +/- 90 pg/mL, respectively. The corresponding levels in the SRO-treated group were 463 +/- 217 pg/mL and 185 +/- 95 pg/mL, respectively. In the amniotic fluid, the concentration was 74 +/- 42 pg/mL in the tablet group and 45 +/- 14 pg/mL in the SRO group. Therefore, isradipine passes the placental barrier, but its concentration is considerably lower in the fetal compartments. PMID- 8466719 TI - Parenteral isradipine reduces blood pressure in hypertensive crisis. AB - The efficacy and tolerability of an infusion of isradipine, a calcium antagonist of the dihydropyridine type, were tested in patients in hypertensive crisis. Ten patients with symptomatic and significant elevations in blood pressure were infused for 12 h with isradipine at 1.2, 2.4, 4.8, and 7.2 micrograms/kg/h (3 h of each infusion level). No untoward effects or adverse reactions were noted. No alterations were observed on electrocardiographic tracings, and blood pressure was significantly reduced only at doses of 7.2 micrograms/kg/h. Thus, isradipine as an infusion is useful and safe for hypertensive crisis, starting at a rate of 7.2 micrograms/kg/h. Higher doses may yet prove to be safe, well tolerated, and even more efficacious. PMID- 8466721 TI - Short- and long-term perspectives of antihypertensive therapy. An introduction. AB - Randomized trials of antihypertensive therapy are relatively short in duration (3 to 5 years) and, when based on monitoring of the mortal and morbid events occurring during this period of time, represent short-term perspectives of antihypertensive therapy. In cases of mild-to-moderate hypertension, however, the goal of antihypertensive therapy is not the prevention of impending events but, rather, the avoidance or retardation of cardiovascular lesions. These long-term perspectives can only be explored by randomized trials that monitor surrogate endpoints (for example, left ventricular hypertrophy or atherosclerotic plaque development). In the future, more and more antihypertensive drugs will be tested to assess their ability to interfere with both cardiovascular disease and cardiovascular events. PMID- 8466720 TI - Left ventricular function and regression of left ventricular hypertrophy in essential hypertension. AB - Although left ventricular hypertrophy (LVH) is an adaptive response to the increased load imposed on the heart in patients with hypertension, it ultimately is itself a major risk factor for cardiovascular disease. The influence of LVH on left ventricular function and on the coronary circulation, and the occurrence of serious ventricular arrhythmias are the major mechanisms of this increased risk. There is no doubt that regression of LVH occurs, but there are clear differences in this respect among antihypertensive drugs: angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists produce the best response. Whether regression of LVH also causes an improvement in left ventricular function is unclear; various studies using the same drugs have yielded contradictory results. Furthermore, it has yet to be determined whether regression of LVH has a positive influence on the long-term prognosis in such patients; the results of the European Multicenter Study OvA will help in shedding more light on this important question. PMID- 8466722 TI - Hemodynamic changes in elderly hypertensive patients. AB - Hypertension in the elderly is characterized by a disproportionate increase of systolic blood pressure over diastolic blood pressure. Subsequently, in this category of patients, the increase in pulse pressure predominates over the increase in mean arterial pressure, thus highlighting the role of arterial changes in this pattern of hemodynamics. In the presence of normal or reduced cardiac function, the disproportionate increase in systolic pressure is the result of a combination of increases of both arterial stiffness and wave reflections. The former is primarily due to central aortic structural changes with a small contribution by modifications of the smooth muscle tone of the central large arteries. The latter is secondary to the geometric modifications of the arterial system associated with age that are responsible for the increase in wave reflections within the thoracic aorta as a consequence of increases in pulse wave velocity and in reflection points closer to the heart. PMID- 8466723 TI - Calcium antagonists and atherosclerosis. The Multicenter Isradipine/Diuretic Atherosclerosis Study. AB - The Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS) is a double blind, randomized, controlled clinical trial comparing the effects of isradipine and hydrochlorothiazide on the progression or regression of early carotid atherosclerosis in 883 hypertensive patients. Assessment of the outcome is by B mode ultrasonographic measurement of early lesions (as reflected by intimal medial wall thickening) at baseline and semiannually over 36 months. At baseline, the participants' mean age was 58.5 years. The study population was 78.6% male and 72.4% white. The average resting systolic and diastolic blood pressures were 149.8 and 96.5 mm Hg, respectively. Mean total serum cholesterol and low-density lipoprotein (LDL)-cholesterol levels were 216.2 mg/dL and 146.6 mg/dL, respectively. Risk factors for coronary artery disease were balanced at baseline between the two study groups. The mean maximum intimal-medial thickness at baseline (measured in the near and far walls of three segments for both carotid arteries) was 1.17 +/- 0.20 mm; the mean intimal-medial thickness of the single thickest lesion was 2.11 +/- 0.51 mm. Cross-sectional analyses show that intimal medial thickness correlates independently with male gender, age, number of cigarettes smoked per day, levels of LDL cholesterol, systolic blood pressure, and white blood cell count. The MIDAS endpoint results will be available in 1993. PMID- 8466724 TI - Differential effects of antihypertensive agents in experimental and human atherosclerosis. AB - The association between hypertension and atherosclerosis is complex, incorporating endothelial dysfunction, abnormalities of insulin and lipid metabolism, altered vascular biology, and impaired arterial compliance. Results of experimental and human studies suggest that there is heterogeneity in the manifestations of disease and responses to therapy among different animal species, vascular territories, and individual patients. Antihypertensive therapy requires the careful selection of specific agents that reduce blood pressure and preferentially and positively modulate the synergistic interaction of the many facets of disease, with the goal of preventing or regressing atherosclerosis. Angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, and alpha blockers appear to hold the greatest promise in this regard. PMID- 8466725 TI - A multicenter comparison of isradipine and felodipine in the treatment of mild-to moderate hypertension. The Physician's Study Group. AB - The objective of this study was to compare the tolerability of isradipine and felodipine in patients with mild-to-moderate hypertension. Following a 4-week placebo run-in, 143 patients entered a 12-week double-blind multicenter study. Patients were randomized to receive either isradipine (n = 72) or felodipine (n = 71) at a dose of 2.5 mg twice daily. Dose-doubling and the addition of enalapril (2.5 mg once daily) was permitted if diastolic blood pressure (DBP) was > 90 mm Hg at weeks 4 and 8, respectively. Isradipine reduced blood pressure from 165/104 +/- 13/6 mm Hg at baseline to 144/88 +/- 13/8 mm Hg at week 12 (P < .001) whereas felodipine reduced blood pressure from 171/104 +/- 17/6 mm Hg at baseline to 150/92 +/- 19/9 mm Hg at week 12 (P < .001). Similar incidences of headache, flushing, dizziness and tachycardia were reported in both groups. However, the incidence of ankle edema was significantly lower in the isradipine group (14% v 30%) (P = .028). It is concluded that isradipine represents a practical improvement over felodipine in the treatment of hypertension. PMID- 8466726 TI - Isradipine in the treatment of mild-to-moderate hypertension. The Austrian Multicenter Isradipine cum Spirapril Study (AMICUS). AB - The objective of this study was to assess the safety and efficacy of 1.25 to 2.5 mg of isradipine twice daily in patients with mild-to-moderate hypertension, as seen in general practice. A total of 595 patients were treated for 6 months with an initial dose of isradipine at 1.25 mg twice daily. This dose was doubled if normotension (diastolic blood pressure [DBP] < or = 90 mm Hg) was not achieved after 4 weeks of treatment (n = 327). If, after 8 weeks, blood pressure was still not normalized, either the angiotensin-converting enzyme (ACE) inhibitor spirapril at 3 mg (n = 58) or the beta-blocker pindolol at 5 mg (n = 54) was added to the treatment. After 24 weeks, the mean blood pressure decrease with isradipine at 1.25 mg twice daily was 28.5/19.0 mm Hg for systolic blood pressure (SBP)/DBP and, with 2.5 mg isradipine twice daily, 28.4/18.5 mm Hg. There was no relevant change in heart rate. The overall normalization rate for all 595 patients was 78.2%. Side-effects that were considered related or possibly related to treatment were reported in 73 patients (12.3%). Treatment with isradipine plus either spirapril or pindolol was discontinued in 32 patients (5.4%) because of side-effects related, or possibly related, to the study treatment. Blood pressure was also self-recorded in a subgroup of 45 patients. The self-recorded values were 11/6 mm Hg (SBP/DBP) lower than the respective causal readings at the start of active treatment. However, this difference disappeared completely after 8 weeks of treatment. PMID- 8466727 TI - Efficacy, safety, and tolerability of isradipine in hypertension as used in general practice in a developing country (Pakistan). AB - This open-label trial of isradipine was carried out in 3422 outpatients by 893 general practitioners to assess the efficacy, safety, and tolerability of isradipine as monotherapy in mild-to-moderate hypertension. Patients received 2.5 mg isradipine twice daily as monotherapy for 6 weeks following a placebo wash-out period of 1 week. After 6 weeks of active treatment, diastolic blood pressure was significantly reduced from 106 +/- 7.7 to 89.4 +/- 8.0 mm Hg (P < .001). Systolic blood pressure also decreased significantly, from 166.8 +/- 19.6 to 141.8 +/- 15.7 mm Hg (P < .001). Blood pressure was normalized in 75.68% of the patients. A total of 629 patients (19%) reported adverse events, 79 (2.3%) of whom withdrew from the study for this reason. The most common side-effects were headache (8.7%), palpitations/tachycardia (3.8%), vertigo (2.89%) and flushing (1.00%). In conclusion, 2.5 mg isradipine twice daily is a safe, effective, and well tolerated form of monotherapy in the treatment of hypertension in general practice in a developing country (Pakistan). PMID- 8466728 TI - A multicenter, double-blind, randomized, placebo-controlled study of isradipine and methyldopa as monotherapy or in combination with captopril in the treatment of hypertension. The LOMIR-MCT-IH Research Group. AB - This multicenter, double-blind, randomized trial of 1 year's duration compared the safety and efficacy of isradipine, methyldopa, and placebo in 368 men, aged 40 to 65 years, with mild-to-moderate essential hypertension. Initial treatment with isradipine (1.25 mg twice daily), methyldopa (250 mg twice daily), or placebo was started after a wash-out and single-blind placebo period. If normotension [diastolic blood pressure (DBP) < 95 mm Hg] was not achieved, doses were doubled. If the maximum dose as monotherapy did not result in normotension, captopril (25 mg or, if necessary, 50 mg, once daily) was added to the treatments of the three patient groups. Despite the marked placebo effect during the first 2 weeks of treatment, monotherapy with isradipine resulted in a higher rate of normalization (more than 64%) compared with 50% in the methyldopa group and 36% in the placebo group. Adding captopril to the treatments of non-responders increased the rate of normalization to 90% in the isradipine group, 84% in the methyldopa group, and 75% in the placebo group. Twenty-one patients dropped-out and 70 patients discontinued the study, the majority because of a lack of efficacy and adverse reactions. The most common adverse reactions reported were cardiovascular and gastrointestinal complaints, headaches, and sleep and sexual disorders, mostly by patients taking methyldopa. Isradipine was well tolerated and the side-effects were minimal. These results indicate that isradipine is superior to methyldopa and, whether as monotherapy or in combination with captopril, highly effective and well tolerated in the treatment of mild-to moderate hypertension. PMID- 8466729 TI - A review of the short-term benefits of antihypertensive treatment with emphasis on stroke. AB - Hypertension is the major underlying risk factor for stroke, and the risk of stroke increases proportionally to the rise in blood pressure. In the elderly, systolic hypertension increases the risk of stroke. Stroke in hypertensive patients may be due to Charcot-Bouchard aneurysm, to atherosclerosis of the extracranial and major cerebral arteries, or to embolism as a result of cardiac disease. Reduction of blood pressure greatly reduces the risk of stroke in severe, mild-to-moderate, and isolated systolic hypertension. The reduction in stroke risk occurs up to a year after the onset of treatment and appears to persist thereafter. The use of dihydropyridine calcium antagonists may confer further benefits in addition to those related to blood pressure reduction as these agents block the influx of calcium into ischemic brain cells, thereby limiting the extent of the infarction. However, although these effects have been impressive in experimental models, there is as yet no convincing evidence of this effect in clinical studies. PMID- 8466730 TI - Reexamining the quality of life of hypertensive patients. A new self-structured measure. AB - This study included the introduction of a new, qualitative, self-structured measure of quality of life (QOL) after meta-analysis had shown that prestructured quantitative measures yielded insignificant results. This study compared the pre- and post-treatment evaluations of 268 men with mild hypertension, aged 40 to 65 years, who were randomly allocated to three treatment groups (methyldopa, isradipine, and placebo) with that of 155 normotensive subjects. It was found that the study participants defined QOL qualitatively differently from the way it was defined by physicians. Normotensive subjects showed a better QOL status in most prestructured measures whereas the patients taking isradipine showed better results on evaluation of the current level of their self-defined domains. The combined quantitative and qualitative approach to measuring QOL may help to clarify this important aspect of medical research, both conceptually and methodologically. PMID- 8466731 TI - Antihypertensive effect of isradipine on ambulatory and casual blood pressure. AB - The antihypertensive effect of isradipine was studied in 35 mild-to-moderate hypertensive patients (mean age 57 years) using casual and ambulatory 24-h blood pressure measurement. After the placebo phase, oral treatment was started with 1.25 mg isradipine twice daily for 4 weeks, which was increased to 2.5 mg twice daily if blood pressure was not normalized [in one patient, the new angiotensin converting enzyme (ACE) inhibitor spirapril was added at a dose of 3 mg daily after 4 weeks]. The active-treatment period lasted 24 weeks. At the end of therapy, casual blood pressure decreased significantly (P < .001) from 174/103 to 151/86 mm Hg, and mean ambulatory blood pressure from 145/88 to 139/84 mm Hg (P < .05). The total number of hypertensive systolic and diastolic blood pressure values also decreased. When patients were divided into normotensives and hypertensives according to their initial ambulatory blood pressure, no effect of treatment was detected in the normotensive group. Casual blood pressure was higher than the 24-h ambulatory pressure. PMID- 8466732 TI - Bioequivalence of a slow-release and a non-retard formulation of isradipine. AB - Pharmacokinetic studies were carried out in 48 healthy male volunteers to determine the pharmacokinetic properties of a new modified-release formulation of isradipine (SRO) and to compare these with the pharmacokinetic properties of the nonretard form of isradipine (NR). Studies were carried out in the fasting state and also following a light meal. The time required to reach maximum plasma concentration (tmax) was extended from approximately 1.5 h with NR to 5 to 7 h with SRO, and the maximum plasma concentration [Cp(tmax)] was reduced by around 50%. The bioavailability of SRO was increased by less than 20% compared with the same daily dose given as NR, indicating that the two forms are bioequivalent and that no adjustment in the total daily dose of isradipine is necessary when switching from one form to the other. Administration with a light meal altered the pharmacokinetic parameters by less than 20% compared with administration without food. PMID- 8466733 TI - Isradipine: a slow-release formulation given once daily controls blood pressure for 24 h. AB - A total of 190 patients (mean age 57 years; range 21 to 89 years), with a supine diastolic blood pressure (sDBP) of 100 to 120 mm Hg after a 3-week placebo phase, entered a double-blind parallel-group study to receive placebo (n = 62), or slow release isradipine (SRO) at 2.5 mg (n = 64) or 5 mg (n = 64) once daily for 4 weeks. Blood pressure was always measured between 23.5 and 24.5 h after the previous drug administration. Before and after the 4-week treatment period, blood pressure profiles were recorded from measurements taken immediately before drug administration ('trough') and repeated at 2, 4, 6, and 8 h after administration. A 'peak:trough' ratio was assessed from the data of 156 patients who completed the 4 weeks of active treatment, and for whom blood pressure profiles were available both before and after treatment. A supine DBP of < or = 90 mm Hg at trough was achieved by 28%, 35%, and 47% of patients receiving placebo, 2.5 mg, and 5 mg SRO, respectively. If patients who achieved a reduction in sDBP of at least 10 mm Hg are included, the total response rate becomes 42%, 66%, and 61% in the three treatment groups, respectively. The reduction in sDBP immediately before drug administration (trough effect) was 37% of the 'peak' effect (6 h after administration) with the 2.5-mg dose and 74% with the 5-mg dose. Adverse events were reported by 14.5%, 9.4%, and 17.2% of patients taking placebo and SRO at 2.5 mg and 5 mg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466734 TI - Efficacy of slow-release oral isradipine in moderate-to-severe hypertension with add-on spirapril. AB - The new slow-release oral formulation (SRO) of isradipine, a dihydropyridine calcium antagonist, was evaluated in 57 patients who had moderate-to-severe hypertension following a 2-week wash-out period and a 2-week placebo period. The angiotensin-converting enzyme (ACE) inhibitor spirapril, at a dose of 6 mg/day, was added to the treatment of those not responding to 5 mg/day isradipine SRO alone. After 4 weeks of active treatment, isradipine alone normalized blood pressure (diastolic blood pressure < or = 90 mm Hg) in 38 (66.6%) patients whereas a further 4 weeks of treatment with the combination of isradipine and spirapril led to normalization in 14 of the 19 (73.7%) patients with partial or nil blood pressure responses. Side-effects were mild and transient and were observed in nine patients (15.8%). Isradipine SRO is an effective and well tolerated antihypertensive agent and combination with spirapril appears to enhance its efficacy without an increase in side-effects. PMID- 8466735 TI - A comparative study of isradipine SRO and enalapril in black patients with mild to-moderate hypertension. AB - Fifty-two black men who had supine diastolic blood pressures (DBP) above 95 mm Hg at the end of a 2-week placebo wash-out period were randomized to receive either isradipine SRO at 2.5 mg/day or enalapril at 10 mg/day for 8 weeks. After 4 weeks, the dosages were doubled if DBP remained above 90 mm Hg. Reductions in blood pressure were comparable in both groups. Mean supine DBP was reduced from 100.6 to 93.9 mm Hg in the isradipine-treated group, and from 103.9 to 98.2 mm Hg in the enalapril-treated group. At the end of the study, 24/27 patients were taking 5 mg isradipine SRO once daily, and 20/25 patients were taking 20 mg enalapril once daily. There were no serious adverse events. The results of this study indicated that monotherapy with isradipine SRO at the recommended initial dosage of 5 mg once daily is appropriate in black patients with hypertension. This was, however, not the case with enalapril at 10 mg once daily. The concurrent administration of a diuretic with enalapril may be more appropriate. PMID- 8466736 TI - Regression of left ventricular hypertrophy with isradipine antihypertensive therapy. AB - To assess left ventricular (LV) structural and functional changes, 45 hypertensive patients were studied by echocardiography after 2 weeks of placebo and 6 months of isradipine monotherapy. Although LV cavity size did not change, LV wall thickness decreased dramatically (P < .0001), producing a significant decrease in LV mass index (from 158 g/m2 to 136 g/m2; P < .0001). In addition, LV fractional shortening (FS) did not change (1.2%; P = NS) whereas the cardiac index increased (6.4%; P = .0007) due to a modest tachycardia accompanied by a reduction in total peripheral resistance (-22.1%; P < .0001). The magnitude of the reduction of LV mass was related to the degree of FS increase (r = -0.70; P < .0001), an indication of beneficial LV remodeling. It can be concluded that isradipine antihypertensive therapy leads to regression of LV hypertrophy without depression of LV pump function. PMID- 8466737 TI - Regression of left ventricular hypertrophy with isradipine in previously untreated hypertensive patients. AB - The regression of left ventricular hypertrophy (LVH) is considered a desirable goal of antihypertensive treatment. Isradipine was used as first-line antihypertensive treatment in 15 patients who had mild-to-moderate hypertension and LVH, and who were studied before and after 6 months of treatment. Left ventricular mass and function were assessed by Doppler echocardiography. Systolic and diastolic blood pressure were reduced from 161 +/- 14 mm Hg and 103 +/- 3 mm Hg to 136 +/- 8 mm Hg and 87 +/- 6 mm Hg, respectively (P < .001). The interventricular septal thickness was reduced by 11.9% (P < .001), posterior wall thickness by 11.1% (P < .001), left ventricular end-diastolic diameter by 2%, and left ventricular mass index by 17% (P < .02). In conclusion, 6 months of antihypertensive treatment of mild-to-moderate hypertension with isradipine achieves a significant regression (17%) of LVH. PMID- 8466738 TI - Reversal of left ventricular hypertrophy with isradipine induces diminution of cardiac arrhythmias. AB - The left ventricular hypertrophy (LVH) of hypertension is often associated with ventricular arrhythmias, which may increase the risk of cardiovascular mortality. Our study was therefore designed to assess whether pharmacological reversal of LVH was associated with the diminution of LV ectopic beats. The antihypertensive agent selected for the study was the dihydropyridine calcium antagonist isradipine (2.5 to 5.0 mg/day orally), which induces rapid regression of LVH. A marked temporal association was observed between regression of LV mass and reductions in the total number of ventricular extrasystoles and in paired beats. Furthermore, there was a diminution of the complexity of the form of ventricular ectopic beats during antihypertensive treatment. No changes in serum electrolytes were documented to account for this control of cardiac arrhythmias. We conclude that the reversal of LVH obtained with isradipine is accompanied by control of the ventricular arrhythmias in hypertensive patients. It is possible that this cardioprotective action may be associated non-specifically with the reduction in LV mass, although a drug- or class-specific action cannot be ruled out. PMID- 8466739 TI - Clinical value of ambulatory blood pressure monitoring. AB - Although office blood pressure measurement may be predictive of cardiovascular complications, it still has several limitations: first, the accuracy of its predictions is limited; second, the stress reaction it causes may lead to an overestimation of the need for treatment and to an underestimation of the therapeutic response in some patients; and third, because of this 'white-coat' reaction and the wide variation in blood pressure over 24 h, office blood pressure can only be an approximate reflection of 24-h average blood pressure values both during and in the absence of treatment. The alternative method of ambulatory blood pressure monitoring may represent a valuable approach in the clinical management of hypertension. Values derived by this method are largely devoid of the consequences of the 'white-coat' reaction and are more closely correlated to the organ damage associated with hypertension than those derived from office blood pressure measurement. However, longitudinal studies are needed to demonstrate whether ambulatory blood pressure monitoring is truly prognostically superior to the traditional method, and to determine precisely which are the blood pressure values within the 24-h period on which to base the diagnosis of hypertension to assess more accurately the efficacy of antihypertensive treatment. However, there is the suggestion that optimal blood pressure control probably consists of an even reduction of both daytime and night time values, and that the wide variations in blood pressure that occur throughout 24 h should probably also be reduced and maintained on a long-term basis. PMID- 8466740 TI - Effect of short-term antihypertensive therapy on left ventricular wall tension. A double-blind comparison of isradipine and nifedipine. AB - The comparative efficacy of the calcium antagonists isradipine and nifedipine in reducing left ventricular peak systolic wall tension was assessed in 25 patients with essential hypertension (20 men, 5 women; mean age: 49 years). After 2 weeks of treatment with either isradipine (2.5 mg twice daily) or slow-release nifedipine (20 mg twice daily), blood pressure was similarly reduced in both groups of patients whereas the thickness of the interventricular septum and left ventricular free wall did not change. Echocardiographic end-diastolic volume of the left ventricle showed no change whereas end-systolic volume significantly decreased with isradipine, but not with nifedipine retard. This led to a significant reduction in peak systolic wall tension in the isradipine group, but not in the nifedipine group. In conclusion, antihypertensive treatment with isradipine produces a reduction in peak systolic wall tension which is not seen with nifedipine, probably because of its negative inotropic effect. PMID- 8466741 TI - Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension. AB - The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients with mild essential hypertension were entered into a double-blind crossover study. Examinations were carried out after 2 weeks of placebo run-in, and after 6 and 12 months of active treatment. Mean resting blood pressure was reduced from 115 +/- 12 mm Hg to 106 +/- 12 mm Hg with atenolol, and to 107 +/- 8 mm Hg with isradipine. The increase in the product of heart rate times blood pressure was significantly greater during isradipine treatment, as was the maximum exercise capacity. Left ventricular mass was increased from 228 +/- 36 g to 305 +/- 68 g with atenolol whereas it remained unchanged with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility. PMID- 8466742 TI - Treatment of hypertension with calcium antagonists and aspirin. Effects on 24-h platelet activity. AB - The effects of calcium antagonists on platelets, and the effects of aspirin on the antihypertensive efficacy of calcium antagonists and on the 24-h platelet activity profile were investigated in a double-blind study. Patients with essential hypertension were treated for 8 weeks with either nitrendipine (10 mg once daily) or isradipine (2.5 mg once daily). Aspirin (100 mg once daily) was added to both treatments for a further 8 weeks. Measurements were taken after placebo, after 8 weeks of active treatment, and after 8 weeks of treatment plus aspirin. Plasma levels of beta-thromboglobulin (beta-TG) and platelet aggregation (PA) were measured six times over 24 h. Isradipine and nitrendipine significantly lowered systolic and diastolic blood pressure. The addition of aspirin had no effect on blood pressure. Platelet activity before treatment exhibited circadian variations with the lowest values of beta-TG and PA at 0530 h and the steepest increases between 0530 and 0900 h. Although both calcium antagonists decreased beta-TG levels (P < .05), the effect with isradipine was more pronounced than that with nitrendipine (P < .05). Aspirin added to nitrendipine produced a significant decrease in beta-TG levels whereas isradipine plus aspirin was accompanied by a partial increase in beta-TG. It is concluded that hypertensive patients exhibit circadian increases in platelet activity that can be prevented by either isradipine alone or by treatment with nitrendipine plus aspirin. Chronic aspirin intake at a daily dose of 100 mg does not affect calcium antagonist antihypertensive efficacy. PMID- 8466743 TI - Minimally invasive surgery in otorhinolaryngology. AB - Otorhinolaryngology has always strived to improve the diagnostic and therapeutic possibilities of managing afflicted organs by developing technically and conceptually new and advanced treatment techniques. The endeavor to develop methods with minimized patient discomfort during interventional surgery in the head and neck region was an essential motive which gave rise to the discipline of ENT medicine. Since fairly recently, the term "minimally invasive surgery" has become firmly established in the domain of general surgery. The possibility for replacing a substantial number of routine operations by endoscopic procedures with low levels of discomfort for the patient and shorter periods of hospitalization has given the term "minimally invasive" even further wide-ranging significance. The present review endeavors to provide an assessment of the current state-of-the-art in otorhinolaryngology, giving special attention to the historical development and pathophysiological fundamentals of this field. PMID- 8466744 TI - Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: a prospective comparative study. AB - Although palpation has proved to be an unreliable staging procedure, the indications for and the implications of more reliable radiologic staging methods for the neck in patients with a primary squamous cell carcinoma of the head and neck remain controversial. Only a very accurate imaging technique can replace neck dissection in clinical NO disease. This study compares the value of palpation with computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) with or without guided aspiration cytology for neck node staging. One hundred and thirty-two patients with squamous cell carcinoma of the head and neck were examined radiologically before undergoing a total of 180 neck dissections as part of their treatment. CT, US and MRI proved to be significantly more accurate than palpation for cervical lymph node staging. The accuracy of US guided aspiration cytology was significantly better than of any other technique used in this study. Modern imaging techniques are essential for appropriate assessment of neck node metastases. In view of advances in the accuracy of contemporary imaging, the need for elective treatment of the neck requires reappraisal. PMID- 8466745 TI - Vascular patterns of the saccule of the rat: a microcorrosion cast study. AB - A scanning electron microscope study of corrosion cast preparations of the vessels of the saccule was carried out in adult rats. This method shows the microvasculature of the saccule in the three-dimensional model. As a result of this technique we have been able to demonstrate a particular microvasculature of the saccule in the rat's inner ear. The main blood supply of the saccule consists of the arterioles coming from the vestibulocochlear artery entering the anterior margin of the macula sacculi. A few branches of the anterior vestibular artery enter the macula sacculi from the superior margin. The saccular vein drains the venous blood from a dense capillary area underneath the striola to the posterior vestibular vein which eventually ends in the vein of the cochlear aqueduct. PMID- 8466746 TI - The effects of low-frequency ultrasound on the inner ear: an electrophysiological study using the guinea pig cochlea. AB - By examining 218 albino guinea pigs, electrophysiological methods were used to investigate the effects of low frequency ultrasound at moderate sound pressure levels after long-term exposure to the inner ear. From 10 kHz to 28 kHz, low frequency ultrasound below 100 dB SPL induced significant changes in cochlear microphonics, elevated thresholds and decreased maximum output voltage of action potentials and decreased absolute values of negative potentials of the endocochlear potentials. PMID- 8466747 TI - Influenza A modification of endotoxin-induced otitis media with effusion in the guinea pig. AB - A total of 120 Hartley strain guinea pigs were used to investigate the possible role of influenza A in endotoxin-induced otitis media with effusion. Intratympanic inoculation of 0.2 ml physiologic saline solution containing 10(4) plaque-forming units (PFU)/ml of influenza A suspension or 100 ng/ml lipopolysaccharide failed to induce either middle ear effusions or mucociliary pathologies in the tubotympanum. In contrast, intratympanic inoculation 100 ng/ml endotoxin resulted in prolonged mucociliary dysfunction and middle ear effusions when 0.2 ml 10(4) PFU/ml of influenza A was inoculated in the tympanic cavity. The inference is drawn that an influenza A infection might predispose the middle ear to endotoxin-induced otitis media with effusion. PMID- 8466748 TI - Preclinical detection of initial vestibulocochlear abnormalities in a patient with multiple sclerosis. AB - A 49-year-old woman presented with a third-degree continuous spontaneous nystagmus to the left which was followed by a sudden, almost complete deafness of her left ear. These symptoms were established as the sole initial presenting manifestations of multiple sclerosis (MS). Magnetic resonance imaging demonstrated a lesion within the left eight nerve root-entry zone and multiple small central lesions beneath the lateral ventricles. Pure-tone audiometry returned to normalcy after 2 weeks and speech discrimination was 100% after 10 weeks. Auditory brainstem responses (ABRs) showed abnormal parameters during a 10 month follow-up period after the acute hearing loss. Furthermore, desynchronization in ABR testing could be demonstrated 2 days before onset of hearing loss, which was interpreted as a prodromal ABR sign of the incipient MS attack. PMID- 8466749 TI - The cochlear glomeruli in the modiolus of the guinea pig. AB - The cochlear glomeruli were studied in guinea pigs using scanning electron microscopy of vascular corrosion casts and transmission electron microscopy of tissue sections. Two types of coiled vessels forming the cochlear glomeruli were found in the bony wall of the modiolus. First, upper glomeruli were seen situated in the bony wall next to the scala vestibuli; second, lower glomeruli were located in the osseous spiral lamina just above the spiral ganglion. Upper glomeruli gave rise to radiating arterioles which supplied capillaries of the stria the spiral lamina and limbus. Unlike the main supplying arteries, smooth muscle cells were not present in the walls of the arterioles forming the glomeruli and a peculiar layer of lamellar pericytes was found. The arterioles were strikingly longer than their parent vessels and no autonomic nerves were found in close spatial relationship. Hence, these findings indicate that the cochlear glomeruli serve as efficient devices for reducing cochlear blood pressure. PMID- 8466750 TI - The effect of nimodipine on salicylate ototoxicity in the rat as revealed by the auditory evoked brain-stem response. AB - Experiments have been performed to investigate the ototoxic effects of sodium salicylate administration in anaesthetised rats as recorded by the auditory evoked brain-stem response (AEBR). Sodium salicylate (300 mg kg-1 i.p.) produced time-dependent increases in hearing threshold and decreases in the four principle peaks of the AEBR. Maximum responses were obtained at 4 h post-administration and were highly significant (P < 0.001). In a further series of experiments nimodipine, a calcium channel antagonist which has been suggested as a potential therapy for tinnitus, was administered at a dose of 2 mg kg-1 s.c. at the same time as sodium salicylate. This had no effect on the changes in hearing threshold. However, it did reduce the decrease in latencies of three of the four peaks of the AEBR, such that only the decrease in latency of the first peak was significantly different when compared to the pre-injection control latency (P < 0.01). We believe that these findings show specific neurophysiological correlates of salicylate ototoxicity. Since salicylate intoxication is used as the method for inducing tinnitus in animal models, the changes in the AEBR may provide an objective measure by which potential therapeutic intervention may be tested. PMID- 8466751 TI - A critical analysis of human immunodeficiency virus transmission using human cartilage allografts. AB - Allogeneic cartilage represents an important source of tissue for reconstructive surgery in the head and neck. The use of allografts is now being discussed because of the possible transmission of the human immunodeficiency virus (HIV). The receptor for HIV in most cell types is the CD-4 molecule. Since cartilage is a popular homograft source, the purpose of this study was to investigate the presence of CD-4 molecules on cartilage tissue as detected with an immunoperoxidase staining and immunofluorescence flow cytometric analysis using a monoclonal antibody. Our results indicate clearly the absence of the HIV receptor on human cartilage tissue. We have concluded therefore that normal cartilage tissue cannot be infected by HIV, at least not through a CD-4-dependent mechanism. PMID- 8466752 TI - Chondrosarcoma of the nasal septum: surgical considerations on Le Fort I osteotomy. AB - A case of chondrosarcoma of the nasal septum extending into the entire nasopharynx sphenoid sinus and skull base is presented. These cartilaginous tumors are rate in the head and neck, with only 28 reported in the nasal septum. They arise in tissues known to be formed of cartilage, and in the present case tumour presumably originated from the perpendicular lamina of the septum. The treatment of choice is wide surgical excision, which requires an adequate approach for gaining the widest possible exposure of tumor. Surgical considerations are discussed. PMID- 8466753 TI - Transcriptional regulation of vascular endothelial growth factor gene expression in ovarian bovine granulosa cells. AB - The expression of vascular endothelial growth factor (VEGF) in cultured bovine granulosa cells has been studied. As shown by northern blot analysis, granulosa cells express the VEGF gene. Analysis of the VEGF transcripts by the polymerase chain reaction technique shows that granulosa cells express predominantly the smallest VEGF coding forms (VEGF121 and VEGF164). Since in the promoter region of the VEGF gene there are four potential AP-1 sites and two potential AP-2 sites we have studied if TPA and forskolin could regulate VEGF gene expression. TPA induces VEGF transcription in a time- and dose-dependent fashion. Maximal VEGF mRNA levels are detected 6 h after TPA treatment. Induction apparently requires de novo protein synthesis since it does not occur when translation is inhibited by cycloheximide. Forskolin, a naturally occurring diterpene that activates adenylylcyclase, also increases VEGF mRNA content in a time-dependent manner. Induction does not require de novo protein synthesis and, in contrast to TPA, induction is strongly potentiated by cycloheximide. Luteotrophic hormone, a known activator of adenylylcyclase, also induces VEGF transcription. These results imply that granulosa cells may be a source of VEGF which could play a role in the angiogenic process associated with ovulation and corpus luteum formation. PMID- 8466754 TI - Midkine (MK), a retinoic acid (RA)-inducible gene product, produced in E. coli acts on neuronal and HL60 leukemia cells. AB - We have shown previously that (i) retinoic acid (RA), an anti-neoplastic agent, activates the midkine (MK) gene in mammalian embryonic carcinoma cells, and that (ii) the MK of 118 amino acids, purified from L cells, induces neurite outgrowth of mammalian embryonic brain cells. In this paper, we describe an unconventional strategy for the purification of a fully active MK from E. coli with a high yield. The MK was overproduced in E. coli as a glutathione S-transferase (GST) fusion protein. The MK fusion protein extracted from the bacterial inclusion bodies with guanidine-HCl was renatured, refolded slowly and cleaved by thrombin at the site where the GST links to the MK. The purified free MK, like RA, induced neurite outgrowth from central neurons of the mouse spinal cord, and suppressed the growth of human HL60 leukemia cells in vitro. Unlike RA, however, the MK did not induce granulocytic differentiation of HL60 cells. Furthermore, the MK supported the survival of an NGF-insensitive sensory neuron subpopulation(s) from chicken embryo dorsal root ganglion. Thus, the actions of the MK and leukemia inhibitory factor (LIF) are surprisingly similar. There is no sequence similarity between MK and LIF, however, and unlike MK, LIF production does not appear to be RA-inducible. PMID- 8466755 TI - Translation of the placenta growth factor mRNA is severely affected by a small open reading frame localized in the 5' untranslated region. AB - The recently identified placenta growth factor gene (PIGF) code for a protein related to the vascular permeability factor (VPF). We present evidence indicating that expressing of this gene could be regulated at the post-transcriptional level. The region upstream to the coding region of PIGF mRNA contains a small open reading frame (ORF), potentially coding for a peptide of 15 amino acids. The translation of different constructs in reticulocyte and wheat germ lysates as well as in COS-1 and CV-1 cells indicates that this short region is a translational inhibitory element since mutations in its two potential initiator codons increase PIGF synthesis in vivo. Using RNAse protection assay, we demonstrate that the PIGF mRNAs obtained from human term placenta and JEG choriocarcinoma cell line have a complete 5' untranslated region and, consequently, also the above mentioned small ORF. Finally, the analysis of a bovine PIGF genomic clone reveals that this small ORF is strongly conserved with respect to both putative peptide sequences and distance from the PIGF coding region. PMID- 8466756 TI - Vitamin D3 and calcipotriol enhance the secretion of transforming growth factor beta 1 and -beta 2 in cultured murine keratinocytes. AB - Vitamin D3 and its analogue calcipotriol (MC 903) inhibit the proliferation of cultured keratinocytes and induce their differentiation. Since TGF beta s are very potent inhibitors of keratinocyte growth we studied the effects of vitamin D3 and calcipotriol on the secretion of TGF beta in cultured murine keratinocytes. Vitamin D3 and calcipotriol (10(-6)-10(-9) M) inhibited the DNA synthesis of mouse keratinocytes by 50-80% in a time and dose-dependent manner as measured by [3H]-thymidine incorporation. Analysis of the conditioned medium of the keratinocytes indicated that the cells secreted into their medium activity that inhibited the growth of indicator Mv1Lu mink lung epithelial cells. Neutralizing antibodies against TGF beta 1 and TGF beta 2 decreased, and when used together, prevented the observed growth inhibition of the indicator cells. Heat treatment of the conditioned medium, which activates latent forms of TGF beta, revealed higher levels of growth inhibitory activity in the medium from vitamin D3 and calcipotriol treated than from control cultures indicating that a fraction of TGF beta was in a latent form. Active TGF beta was, however, detected considerably more in vitamin D3 and calcipotriol treated cultures than in control cultures. Immunoblotting analysis of the medium revealed enhanced secretion of TGF beta protein. These results indicate that enhanced TGF beta 1 and TGF beta 2 secretion and activity is associated with vitamin D3-mediated growth inhibition of cultured keratinocytes. PMID- 8466757 TI - A model for the interaction of the GM-CSF, IL-3 and IL-5 receptors with their ligands. AB - The high affinity receptors for GM-CSF, IL-3 and IL-5 are heterodimers consisting of a ligand-specific alpha chain and a common beta chain. These proteins are members of a family of proteins known as the "cytokine receptor family" which is characterized by the presence of a 200-residue ligand-binding module. The GM-CSF, IL-3 and IL-5 receptor alpha chains constitute a distinct subgroup and share features not found in other members of the cytokine receptor family, features which we propose to be important for their interaction with the common beta chain and for their binding of the structurally-related ligands. The growth hormone receptor is a well-characterized member of the cytokine receptor family. Based on the structure of the complex between growth hormone and its receptor, we have proposed sites of contact between the GM-CSF, IL-3 and IL-5 receptors and their cognate ligands. PMID- 8466758 TI - Starting again--a comparison study of a group rehabilitation program for cancer patients. AB - The effects of a seven-week (11 two-hour sessions) group post-treatment rehabilitation program ('Starting again') for cancer patients were assessed. The program emphasised physical training, information, and training of coping skills. Thirty participants were matched to thirty patients, not wanting to participate (comparison group) and compared in a longitudinal study: before and after the program, and three, six and twelve months after program completion. Program participants had a significantly heavier burden of physical and psychological symptoms at entry than did patients who chose not to participate. More participants reported change of their life-style and habits after the cancer diagnosis than did the comparison group. In comparison with non-participants, participants were more satisfied with information during the entire follow-up, improved more from pre- to post measurement with respect to physical strength and increased their physical training and social activities more. PMID- 8466759 TI - Protein tyrosine kinase in colorectal adenoma. AB - To determine whether protein tyrosine kinase (PTK) could be utilized as a biological indicator of colonic tumorigenesis, we examined the PTK activity in the cytosolic and particulate fractions of homogenates from 25 adenomas (polyps) and from adjacent normal mucosa. The particulate fraction PTK activity in the colorectal adenomas was significantly higher than in the normal mucosa. The adenomas were then analyzed according to size, histological type (tubular and tubulovillous), and degree of dysplasia (mild, moderate and severe). The average particulate fraction PTK activity ratio (adenoma/normal mucosa) of tubulovillous adenomas or adenomas with moderate to severe dysplasia was significantly elevated in comparison with that of tubular adenomas or adenomas with mild dysplasia. The particulate PTK activity ratio increased significantly with increasing adenoma size, while the cytosolic ratio did not. The cytosolic PTK activity ratio in tubulovillous adenomas or adenomas with severe dysplasia decreased significantly with increasing size. These findings suggest that colonic carcinogenesis might be associated with alterations in the cellular level of PTK activity and that the PTK activity ratio (adenoma/normal mucosa) in the particulate and/or cytosolic fractions may possibly correlate with the risk of malignant transformation. PMID- 8466760 TI - Urinary excretion of 6-hydroxymethylpterin in brain tumours. AB - The urinary 6-hydroxymethylpterin(Pt-6-CH2OH) excretion was determined in 87 patients with brain tumours and in 50 control patients. The Pt-6-CH2OH levels were significantly elevated in all patients with tumours. No difference was observed when malignant tumours were compared with benign neoplasms. Following therapy, the Pt-6-CH2OH levels were partially reduced when compared with control patients and their pre-operative values. PMID- 8466761 TI - Breast cancer 2000 BC to 2000 AD--time for a paradigm shift? AB - In this paper I trace the history of the development of the treatment of breast cancer over a 4000-year period. I point out that there have basically been three paradigms within which we have studied and developed treatment for this disease. Clinical trials over the last twenty years as an expression of the scientific method in action, have demonstrated the limited success of the contemporary paradigm with its therapeutic sequelae of breast conserving surgery and adjuvant systemic therapy. At the same time a critical review of the natural history of breast cancer and the results of current treatments suggest logical inconsistencies in the model. I have therefore constructed a novel paradigm which better fits the available information by suggesting that metastases are not only a result of cellular transmission of breast cancer but sub-cellular transmission using the mechanism of in vivo transfection. Although this may sound far fetched, there are a series of remarkable studies in the literature which supports this conceptual revolution. This is surely a fertile field for research and the therapeutic consequences would be obvious. They might suggest that more aggressive adjuvant systemic chemotherapy based on the conventional model is unlikely to achieve any additional benefit, whereas therapy based on anti-viral drugs might produce the next therapeutic advance. It is not the intention of this article to persuade readers that the alternative paradigm is true but merely to open minds to the study of history and scientific philosophy to ensure that we do not repeat the errors of the past. PMID- 8466762 TI - Treatment of relapsing anal carcinoma. AB - Between 1983 and 1989, a total of 94 patients were admitted to the Norwegian Radium Hospital for primary squamous cell carcinoma (including 'basaloid' and 'cloacogenic' carcinomas) of the anal canal. Seven patients with evident distant metastases received chemotherapy, while without known distant metastases received combined chemo- and radiotherapy. Of the latter patients, 17 developed distant metastases and 11 local recurrence later on. Patients with distant metastases had a median survival of 12 months (range 3-54 months) following start of chemotherapy (cisplatin + 5-FU or mitomycin C + 5-FU). An abdominoperineal resection was performed on 9 of the 11 patients with local relapse. Of these, 6 patients were alive without evident disease after 3 years of observation. PMID- 8466763 TI - Megestrol acetate in cancer patients with anorexia and weight loss. A Hellenic Co operative Oncology Group (HeCOG) study. AB - Fifty-two patients with hormone-independent cancer, who complained of anorexia and of weight loss with at least 10%, received megestrol acetate (MA), 480 mg daily, during 1-21 weeks. Of the 41 patients treated during 4 weeks or longer, 38 experienced weight gain. Monthly subjective evaluation of six parameters using a linear analog self-assessment (LASA) form showed a significant improvement in the patient's rating of appetite, mood, nausea and vomiting, and quality of life; the tumor was progressive in 21, stable in 11 and it regressed in only 9 of these patients. No toxicity was observed; one case of death due to a congestive heart failure remains unexplained. MA at the dose used is a powerful appetite stimulant; it contributes to weight increase and might improve the subjective appreciation of quality of life. MA at lower doses should be compared in a prospective trial to the dose used in this study. PMID- 8466764 TI - Reduction of cisplatinum-induced renal toxicity in mice by tetrahydroindazolonecarboxylic acid (HIDA) [corrected]. AB - The ability of tetrahydroindazolone carboxylic acid (HIDA) to reduce the toxicity of cis-diamminedichloroplatinum (cis-DDP) in CDF1 mice was investigated. Toxicity was assessed both in terms of mouse lethality occurring within 14 days after treatment and kidney damage estimated by measurement of plasma urea. The levels of plasma urea were found to increase from day 2 after intraperitoneal (i.p.) injection of cis-DDP, reaching a peak at day 5. This increase was also cis-DDP dose dependent. An i.p. injection of HIDA reduced kidney damage only when given 2.5 h prior to cis-DDP and at HIDA doses of 100 mg/kg or larger. The protection ratio for this reduction was 1.10. HIDA also decreased mouse lethality from cis DDP, resulting in a PR of 1.41. This protective effect of HIDA on cis-DDP toxicity may eventually have a clinical application. PMID- 8466765 TI - A new theoretical formula for fractionated radiotherapy based on a saturable cellular repair mechanism. AB - Recently we have published a new model of survival cellular response to radiation based on the existence of a saturable cellular repair mechanism. In the present paper we extend the predictions of this model of calculating the change in total dose necessary to achieve an equal response in a tissue when the dose per fraction in a radiotherapy fractionation schedule is varied. The model provides a new explanation of the difference between late and early radiation reactions. Results obtained from the model for different tissues and standard fractionation schedules are approximately equal to those obtained by the L.Q. (linear quadratic) model. The model is compatible with in vitro survival curves that are straight at high doses. PMID- 8466766 TI - Radiation therapy of para-aortic lymph nodes in cancer of the uterine cervix. AB - From 1965 to 1986, 173 patients with gynaecological cancer received para-aortic radiation treatment using a biaxial-four-segmental-rotating field technique. Seventy-five patients with cervical cancer and proven lymph node involvement were eligible for analysis. Crude survival and disease-free survival in 37 patients with FIGO III and 15 patients with FIGO IVA, receiving initial para-aortic treatment were compared with the corresponding data from patients in whom para aortic treatment was secondary applied when para-aortic metastases became clinically symptomatic. Five-year survival rates of 37.5% (FIGO III) and 27.3% (FIGO IVA) were encouraging as none of the patients in the secondary group survived for more than 16 months. The number of complications induced by the described method of survived for more than 16 months. The number of complications induced by the described method of para-aortic irradiation appears to be substantially lower than with other methods using equal doses. Five cases of severe but not life-threatening side-effects were observed among 173 treated patients. PMID- 8466767 TI - Radiotherapy compared to chemotherapy as initial treatment of angiocentric centrofacial lymphoma (polymorphic reticulosis). AB - Polymorphic reticulosis has recently been characterized as an angiocentric lymphoproliferative disorder of the peripheral T-lymphocytes. However, its treatment is still a matter of controversy. In order to study efficacy and toxicity of the primary treatment, we reviewed clinical features and therapeutic results in 29 patients seen at the Instituto Nacional de Cancerologia de Mexico. Nineteen patients received primary local irradiation and 10 patients primary combination chemotherapy. In the radiotherapy group, 14 (74%) patients achieved complete response, but only 4 (40%) did so in the primary chemotherapy group. Five patients in the latter group died of treatment-related complications. The 5 year actuarial survival rate was 70% in the irradiation group, while the 1-year survival rate was only 15% in the chemotherapy group. These data strongly suggest that, in polymorphic reticulosis, initial chemotherapy may be very toxic. PMID- 8466768 TI - Backscatter radiation at tissue-titanium interfaces. Biological effects from diagnostic 65 kVp x-rays. AB - The induced secondary electrons from a metal surface by diagnostic x-rays are thought to contribute to cell damage near the tissue-metal boundaries of metal implants. Titanium implants are becoming increasingly more popular for tissue reconstructions and it is rather often desirable to take radiographs of the operated area. In this study we compared the biological effects of radiation on cultured mammalian test cells grown on titanium plates with the radiation effects on cells that were grown on plastic control plates. In order to study the acute radiation effects on cell growth it was necessary to work with rather high radiation doses (0.7-5 Gy). Photon energies, suitable for diagnostic radiography in odontology, 65 kV, were applied. We found that the cells grown on titanium plates were, in terms of the applied dose in the surrounding culture medium, more sensitive to the irradiations than the cells growing on plastic plates. The survival curve for the cells on titanium had a steeper slope, showed no shoulder in the low-dose region and looked like curves normally obtained for high LET radiation. It was not possible to resolve to what degree the titanium-dependent changes were due to an increased dose near the titanium surface or to a change in the radiobiological effectiveness. Although there was a significant decrease in cellular survival near the metal, postoperative intraoral radiography after titanium implantations need not be excluded. The maximal doses given in odontological x-ray examinations are less than 1 mGy and, if the results in this study are applied, the biological effects near the titanium implant will correspond to biological effects in soft tissue of doses less than 20 mGy which is lower than the doses that give acute effects. The risk of acute healing disturbances are significant only at much higher radiation doses. PMID- 8466769 TI - Influence of the timing of a concomitant boost during fractionated irradiation of rat rhabdomyosarcoma R1H. AB - Rhabdomyosarcomas R1H of the rat (WAG/Rij) were treated using fractionation schedules including a boost. The total dose was 60 Gy. Overall treatment time was 6 weeks. Four different boost schedules were applied: a single dose boost (12.15 Gy) at the last day of treatment, a single dose boost (12.15 Gy) at the first day of treatment, a schedule including the boost in 7 fractions during the first week, and a schedule including the boost in 10 fractions during the first week of treatment. A standard schedule with 30 fractions of 2 Gy without a boost was used for comparison. Initially accelerated schedules, i.e. those with a boost at start of treatment, revealed higher effect on tumour parenchyma as monitored by local control rate and net growth delay. This could be due to a decrease of radio sensitivity, that is, an increase of the hypoxic fraction of clonogenic tumour cells during fractionated irradiation. PMID- 8466770 TI - Liver cirrhosis and serum neuron-specific enolase. PMID- 8466771 TI - Discontinuous accelerated fractionation in the treatment of advanced head and neck neoplasms--a preliminary report. PMID- 8466772 TI - Cancer incidence among male salaried employees at a smeltery in northern Sweden. AB - This study focuses on mortality and cancer incidence among the male salaried employees at a copper smeltery in northern Sweden, where previously an increased lung cancer risk had been demonstrated among blue-collar workers, with all likelihood due to arsenic exposure. During the period 1928-1979 there has been 1,255 male salaried employees and 6,334 male blue-collar workers. Three cohorts were formed; those who had worked only as salaried employees, those who had worked only as blue-collar workers and those had worked in both job categories. The mortality among the entire group of salaried employees was comparatively lower than that of Sweden as a whole. The incidence of lung cancer was highest among those who had worked in both job categories, most of them former blue collar workers. The trends in lung cancer incidence among the blue-collar workers along and among those who had had both types of jobs showed the same pattern, with a peak in the 1970s. The decrease in this trend started earlier among the salaried employees. When job category and employment cohort were analyzed together the highest risk was confirmed for those having been employed in both job categories. PMID- 8466773 TI - Stress in undergraduate medical education: 'the mask of relaxed brilliance'. PMID- 8466774 TI - General practice in deprived areas: problems and solutions. PMID- 8466775 TI - Patient access to records: expectations of hospital doctors and experiences of cancer patients. AB - The aim of this study was to examine cancer patients' reactions to the offer of access to their medical records, hospital doctors' preconceptions of patient access to medical records and the reality of access to records for both parties. Semistructured interviews were conducted with 32 patients and 21 hospital doctors. Hospital doctors were also shown letters from their department to the general practitioner and asked about any changes they would have made as a result of knowing about patient access to records. The results showed that most patients were able to judge for themselves if they wanted access or not and that patients who chose to look at their records found access to their records helpful and reassuring even if the news was bad. Doctors expected access to records to be harmful to patients but would not have wished to amend many of the letters they had written. Patient access to records can be a safe and useful adjunct to good patient care. PMID- 8466776 TI - Knowledge and perceptions of a domiciliary hospice service among general practitioners and community nurses. AB - Within a single district health authority all the general practitioners and community registered general nurses were asked to complete a questionnaire regarding awareness and perceptions of a domiciliary hospice service. Responses were received from 127 doctors (71%) and 58 nurses (80%). Awareness of resources offered by the domiciliary hospice service was high, especially among the 102 respondents with access to the service. Eighty per cent or more of general practitioners and community nurses were satisfied with the amount of information received concerning changes in the patient's condition and who was involved in the care process. However, 33% of nurses agreed that it was difficult to know who had overall responsibility for the patient's care and 28% of nurses felt that their own contribution was under-rated. These findings were reinforced by a number of written statements submitted by the nurses. There was a desire expressed by both general practitioners and community nurses for more educational input from the domiciliary service. Overall, assistance from the service was welcomed and its special skills acknowledged. In the future planning of a comprehensive hospice service the differing needs expressed by doctors and nurses should be taken into account. PMID- 8466777 TI - Management of joint and soft tissue injuries in three general practices: value of on-site physiotherapy. AB - A prospective study was undertaken to determine the potential benefits in patient management and cost effectiveness of physiotherapists employed by general practitioners compared with direct hospital access and access via consultants. The study involved 401 patients from three rural general practices in south Cheshire and north Staffordshire and took place over six months. On-site physiotherapy in general practice premises resulted in higher referral rates to the physiotherapist compared with the practice using direct hospital access or the practice with access via consultants. Both on site and direct access physiotherapy were associated with fewer prescriptions and lower overall prescribing costs per patient than access to physiotherapy via consultants. There was less time lost from work and normal duties for patients attending the practice with on site physiotherapy compared with those attending the practice which required referral via hospital consultants. Access to physiotherapy via hospital specialists resulted in considerably longer delays than on site physiotherapy and greatly increased the financial costs for the patient. Physiotherapy in general practice premises is a cost effective way of dealing with joint and soft tissue complaints. Direct access to the physiotherapy department within hospitals results in longer delays but provides a satisfactory service. There is little to recommend the utilization of hospital consultants as a means of access to physiotherapy. PMID- 8466778 TI - Care of diabetic patients in hospital clinics and general practice clinics: a study in Dudley. AB - A five year retrospective casenote review was undertaken of 452 patients attending 11 different general practice diabetic clinics, and 506 patients attending a diabetic clinic at hospital A and 210 patients attending a diabetic clinic at hospital B. The populations attending the clinics, the degree of glycaemic control achieved and the monitoring for the development of diabetic complications were investigated. Insulin dependent patients comprised 57.9% of patients attending the diabetic clinic at hospital A, 35.7% at hospital B and 25.0% of patients attending the diabetic clinics at general practices. Of these 55.6%, 37.3% and 30.1% respectively received multiple daily insulin injections. Hospital A had a higher proportion of patients under 40 years old than hospital B or the general practice clinics. The ages of diabetic patients attending the general practice diabetic clinics were broadly similar to those attending hospital B. Significantly more general practice patients, both insulin and non insulin dependent, had a mean blood glucose level of less than 11 mmol l-1 compared with patients attending clinics at hospitals A and B (P < 0.001). Glycosylated haemoglobin levels did not differ between patients attending hospital A and the general practice clinics. More non-insulin dependent and insulin dependent diabetic patients attending the general practice clinics and hospital A had been monitored satisfactorily for diabetic retinopathy (general practice clinic 68.8% and 39.7% respectively, hospital A 61.7% and 43.5%) than at hospital B (43.0% and 19.4%). Referral rates among all groups for ophthalmological assessment were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466779 TI - Creating a death register for general practice. AB - General practitioners complete approximately 26% of death certificates themselves but have considerable difficulty obtaining prompt and accurate information about their other patients who die. A random survey of district health authorities in England revealed that all were able to compile death lists but none included general practitioner details. This paper reviews the flow of information on patient deaths and describes a project to assess the feasibility of providing Newcastle general practitioners with comprehensive death registers. With the collaboration of the family health services authority and the district health authority, and with data from the regional perinatal mortality survey the creation each week of complete lists of patient deaths, broken down by general practitioner, is feasible. Death registers allow general practitioners to undertake audit of the quality of death certification and of the care of the recently deceased, and to improve the continuing care of the bereaved. PMID- 8466781 TI - James Mackenzie Lecture 1992. The Indians' revenge. PMID- 8466780 TI - Efficacy of physiotherapy for musculoskeletal disorders: what can we learn from research? AB - In order to summarize the available clinical evidence for the efficacy of physiotherapy, 400 randomized clinical trials were identified from the literature. Studies were found by using bibliographic databases, citation tracking, and correspondence with researchers in the field. Focusing on disorders of the musculoskeletal system, a number of criterion based meta-analyses were performed on 180 trials in order to summarize the available evidence. For each randomized clinical trial in each meta-analysis a methodological score was calculated using a set of explicit criteria and weighting factors applied by two or three independent reviewers who were blinded as to the outcomes, the journal and the authors of the publication. In each meta-analysis the randomized clinical trials were ordered hierarchically depending on their score for methodological quality. Meta-analyses were performed for spinal manipulation, exercise therapy, traction, ultrasound, and laser therapy, and for disorders of the back, neck, shoulder and knee. In general, the methodological quality of the studies appeared to be low, and the efficacy of physiotherapy was shown to be convincing for only a few indications and treatments. On the other hand, because of the prevalence of serious methodological flaws, it cannot be concluded that physiotherapy has no effect. PMID- 8466782 TI - Apparent food allergy. PMID- 8466783 TI - Ambulatory blood pressure measurement. PMID- 8466784 TI - Community care of patients receiving antipsychotic medication by depot injection. PMID- 8466786 TI - [Tax tips for nurses]. PMID- 8466785 TI - Emergency contraception. PMID- 8466787 TI - [Norwegian Nurses Association with large-scale campaign: we must entice career minded youths to the nursing profession]. PMID- 8466788 TI - [Student guidance clarified. Interview by Kjell Arne Bakke]. PMID- 8466790 TI - [Sceptical about cooperation in revenue policy]. PMID- 8466789 TI - [First aid 30,000 feet high. Interview by Siv Barstad]. PMID- 8466791 TI - [Pat on the shoulder, less in union's fund. Interview by Bjorn Arild Ostby]. PMID- 8466792 TI - [Nursing under a different sky--Saudi Arabia]. PMID- 8466794 TI - [To Uganda with knowledge. Interview by Kjell Arne Bakke]. PMID- 8466793 TI - [Asia: front-line country in the HIV epidemic]. PMID- 8466795 TI - [The entire family in childbed]. PMID- 8466796 TI - [Professional nurses have a lot of responsibility and many possibilities]. PMID- 8466797 TI - [Special hospital stifles guest patients' arrangement. Unfair to patients]. PMID- 8466798 TI - [Special hospital stifles guest patients' arrangement. Sunnaas struggles. Interview by Siv Barstad]. PMID- 8466799 TI - [Special hospital stifles guest patients' arrangement. Everybody has enough of it]. PMID- 8466800 TI - Analysis of enterotoxin production by Bacillus cereus from dairy products, food poisoning incidents and non-gastrointestinal infections. AB - Of 85 strains of Bacillus cereus isolated in Norway from dairy products, 59% were found to be enterotoxigenic, and 15% were psychrotrophic. Six of the isolates (7%) were identified as potential psychrotrophic food-poisoning strains as they were both enterotoxigenic and exhibited good growth at 6 degrees C. Enterotoxin production was detected using the Western immunoblot technique, and a commercially available reversed passive latex agglutination (RPLA) assay (Unipath BCET-RPLA TD950). Both methods gave essentially the same results. In a separate study, the Western immunoblot and RPLA assays were used in a conjunction with the in vivo vascular permeability reaction (VPR) assay to determine enterotoxin production among 25 isolates of Bacillus cereus referred to the PHLS Food Hygiene Laboratory from incidents of diarrhoeal- and emetic-syndrome food poisoning and non-gastrointestinal infections. Eighty-four percent of these isolates were found to be enterotoxigenic by the Western immunoblot and the RPLA assays, and these results were in good agreement with those obtained by the VPR assay. In both studies, the BCET-RPLA kit proved to be a simple and reliable means for determining enterotoxin production by strains of Bacillus cereus. PMID- 8466801 TI - Detection of Salmonella in animal protein by Rappaport-Vassiliadis broth using indirect impediometry. AB - Indirect impedance methodology for the detection of Salmonella was investigated using a rapid automated bacterial impedance technique (RABIT) system. Four commercially available Rappaport-Vassiliadis (RV) enrichment broths were evaluated for their sensitivity and selectivity in detecting Salmonella using this technique. The RV from Lab M and Oxoid (new) gave the shortest detection times and showed good correlation between Salmonella numbers and detection times. Using Lab M medium, the indirect impedance technique could distinguish between Salmonella spp. and the closely related genera, Proteus and Citrobacter. The impedance technique showed recoveries of Salmonella from processed animal protein and raw meats equivalent to, or better than, those obtained with RV used in a conventional Salmonella isolation procedure. PMID- 8466802 TI - Effect of three preservatives on the growth of Bacillus cereus, Vero cytotoxigenic Escherichia coli and Staphylococcus aureus, on plates with gradients of pH and sodium chloride concentration. AB - The effect of temperature, pH, sodium chloride concentration and a preservative (sodium benzoate, sodium nitrite or potassium sorbate) on the growth of three foodborne bacterial pathogens (Bacillus cereus, Vero cytotoxigenic Escherichia coli and Staphylococcus aureus) was studied using gradient gel plates. Growth, expressed in optical density units, was recorded using image analysis techniques, and was expressed as three-dimensional grids. These gave a visual indication of the effects of any three of the environmental factors on bacterial proliferation. Sorbate was completely effective against E. coli at all temperature/pH/NaCl combinations, and was the most effective preservative tested against B. cereus. Increase in the acidity and/or the NaCl concentration improved the effect of all the preservatives, except nitrite when used against St. aureus. Nitrite was the least effective preservative, particularly against St. aureus. At < 25 degrees C, sorbate was more effective than benzoate against St. aureus when used with higher concentrations of NaCl. At 35 degrees C benzoate was the most effective preservative against St. aureus, especially when used at pH < 6. PMID- 8466803 TI - Effects of gluconodeltalactone and Lactobacillus plantarum on the production of histamine and tyramine in fermented sausages. AB - Fermented sausages were made experimentally with addition of 0.3% (w/w) gluconodeltalactone (GDL) or a starter culture of Lactobacillus plantarum, unable to produce histamine or tyramine. Controls were produced without GDL and starter culture. During 15 days preparation and storage periods, number of bacteria and lactobacilli, pH, and levels of histamine, tyrosine and tyramine were monitored, and organoleptic evaluations were carried out. Maximal histamine levels were 19.41 micrograms/g of dry matter in the GDL-added sausages, 18.64 micrograms/g in the control, and 17.20 micrograms/g in the starter sausages. Maximal tyramine levels were 1249.16 micrograms/g in the GDL sausages, 1101.16 micrograms/g in the control, and 906.35 micrograms/g in the starter sausages. Sausages produced with GDL proved less acceptable in organoleptic evaluation due to an unpleasant sour flavour. PMID- 8466804 TI - Inhibition of the growth of yeasts in fermented salads. AB - Salads composed of vegetables and/or meat in an oil-in-water emulsion were prepared by fermentation for 7 h at 42 degrees C or 45 degrees C with strains of Lactobacillus spp. Their stability towards spoilage yeasts was studied using Saccharomyces cerevisiae, Saccharomyces exiguus and Torulaspora delbrueckii, isolated from salads, as well as Pichia membranaefaciens and Zygosaccharomyces bailii. Salads fermented with good lactic starters usually had pH values of < or = 4.2 and lactic acid concentrations of 0.28 to 0.43% (w/w). High numbers of spoilage yeasts (and production of large volumes of CO2) were not attained in these salads, provided the initial concentration of spoilage yeasts was sufficiently low (< or = 100 CFU/g). Inhibition of spoilage yeasts in lactic fermented salads is probably due to lactic acid, the low storage temperature and the low residual oxygen concentration. PMID- 8466805 TI - Flow cytometric detection of wild yeast in lager breweries. AB - A flow cytometric method for detection of wild yeast infections in breweries is reported. It is based on selective enrichment in Malt extract Yeast extract Glucose Peptone broth (MYGP) at 37 degrees C and in MYGP with 200 ppm CuSO4 at 25 degrees C, staining with a fluorochrome precursor and flow cytometry. In experiments with several types of wild yeast isolated from breweries and two different strains of lager yeast it has been possible to detect one wild yeast per 10(6) culture yeast after 48-72 h of incubation and, in some cases, after 24 h. PMID- 8466806 TI - Survey of the physiological properties of the most frequent yeasts associated with commercial chilled foods. AB - A comparative analysis of the initial and final population of yeasts, lactic acid bacteria and psychrotrophic bacteria, in a number of chilled foods, varying in ingredients, physico-chemical characters and origin, gave evidence that yeasts could play a significant role in the spoilage. The yeast populations appeared to be unexpectedly uniform and comprised principally strains of Yarrowia lipolytica, Debaryomyces hansenii and Pichia membranaefaciens. A survey of 62 isolates, comprising physiological characteristics such as growth temperatures, proteolytic and lipolytic activities, hydrophobicity, aw and preservative tolerance, in addition to organic acid production, indicated that these dominant species have very few common characters and that they are endowed with a spoilage potential probably linked to different physiological properties. The isolates of Y. lipolytica exhibited the strongest proteolytic and lipolytic activities and a pronounced hydrophobicity while D. hansenii isolates were characterized by a high growth rate at low temperature and at intermediate aw. P. membranaefaciens isolates showed a remarkable tolerance to acetic acid as a sole selective factor. A hypothesis of separate growth loci, in multicomponent or polyphasic food systems, was formulated. PMID- 8466807 TI - A 48 kilodalton enterotoxin-related protein from Clostridium perfringens vegetative and sporulating cells. AB - Sporulating and vegetative cell extracts of enterotoxin-positive and enterotoxin negative strains of Clostridium perfringens were examined by Western blotting using enterotoxin antiserum. A 48-kDa enterotoxin-related protein was found in vegetative and sporulating cell extracts of both toxin types. The results question previous reports about the ability of vegetative cells and presumptive enterotoxin-negative strains of this organism to produce enterotoxin, a protein with a molecular weight of 34 kDa. PMID- 8466808 TI - Microbial ecology of fresh pork stored under modified atmosphere at -1, 4.4 and 10 degrees C. AB - The prevalent bacteria on fresh pork packaged in modified atmosphere with elevated CO2 were determined by selection of representative colonies from the greatest dilution of meat samples. The pork samples were stored in two packaging films of different oxygen permeability at three storage temperatures. Strains were classified and those identified as lactic acid bacteria were screened for production of inhibitory substances. The types of bacteria isolated from samples stored in the two packaging films were similar. Storage temperature influenced the type of bacteria that dominated the microbial population. At 10 degrees C the prevalent microflora consisted of aeromonads, Enterobacteriaceae and lactic acid bacteria but at 4.4 and -1 degrees C, aeromonads, Brochothrix thermosphacta and lactic acid bacteria dominated. Listeriae were detected as part of the prevalent microflora on samples stored at -1 degree C, but not on samples stored at 4.4 or 10 degrees C. Species of lactic acid bacteria dominating the microflora were influenced by growth medium. The majority of isolates taken from Plate Count agar were carnobacteria whereas those from Lactobacilli MRS agar were homofermentative lactic acid bacteria. Of the 538 lactic acid bacteria isolates screened for production of inhibitory substances, 162 strains showed deferred inhibition toward a range of lactic acid bacteria and nonlactic acid bacteria indicator strains. PMID- 8466809 TI - A model of food-borne Listeria monocytogenes infection in the Sprague-Dawley rat using gastric inoculation: development and effect of gastric acidity on infective dose. AB - Recent epidemiological evidence suggests that Listeria monocytogenes (LM) is a food-borne pathogen in humans. A model of LM infection was developed using the Sprague-Dawley (SD) rat to study the interaction of LM with gastrointestinal epithelium as the first step in the pathogenesis of invasive listeriosis. Conventionally raised, juvenile female SD rats were given 10(2)-10(9) virulent L. monocytogenes, serotype 4b or nonpathogenic Listeria species. Only rats given virulent LM developed dose-dependent invasive infection of the liver and spleen. Light and electron microscopic studies suggested attachment to and invasion of the gastrointestinal mucosa by virulent LM. Because the development of invasive listeriosis in humans has been epidemiologically associated with a decrease in gastric acidity, the effect of decreasing gastric acidity on dose-dependent infection was studied. Rats were pretreated with cimetidine (50 mg/kg) by intraperitoneal injection prior to oral inoculation of 10(2)-10(9) virulent L. monocytogenes. Cimetidine significantly lowered the infective dose of virulent L. monocytogenes (P < 0.05). This oral model should allow further study of host and organism-specific virulence factors mediating the gastrointestinal phase of invasive LM infection, an increasingly important public health problem. PMID- 8466810 TI - Effect of low-dose irradiation on growth of and toxin production by Staphylococcus aureus and Bacillus cereus in roast beef and gravy. AB - The effect of irradiation (2 kGy) on growth of and toxin production by Staphylococcus aureus and Bacillus cereus in roast beef and gravy during storage at abuse temperatures (15 and 22 degrees C) was assessed by inoculation studies. Irradiation resulted in a 3-4 log10 reduction in numbers of both pathogens. Whenever B. cereus and S. aureus numbers reached 10(6) and 10(7) cfu/g, respectively, during storage their toxins were detectable. As the time taken to attain these levels was longer in irradiated than in unirradiated samples, toxin production by both pathogens was delayed by irradiation. When samples initially containing low levels (10(2)/g) of S. aureus were irradiated no toxin was produced during subsequent storage at 15 or 22 degrees C. Diarrhoeal toxin produced by B. cereus was detected after 2 days at 22 degrees C, but not at 15 degrees C, in samples containing 10(2) cells/g prior to irradiation. When higher numbers (10(6)/g) of either pathogen were present prior to irradiation, toxins were produced by both pathogens at 22 degrees C, but not at 15 degrees C. Microbial competition had an effect on the growth of B. cereus and S. aureus after irradiation when a low initial inoculum was applied. However, when a higher inoculum was used the pathogens outnumbered their competitors and competition effects were less important. It was concluded that low-dose irradiation would improve the microbiological safety of roast beef and gravy. PMID- 8466811 TI - An improved medium for distinguishing between homofermentative and heterofermentative lactic acid bacteria. AB - An improved solid medium for differentiating between homofermentative and heterofermentative lactic acid bacteria is proposed. It was developed to support the growth of wine strains unable to grow in other media. However, it can be employed as a general medium for the lactic acid bacteria that utilize fructose. PMID- 8466812 TI - Within and between sample comparisons of Gompertz parameters for Salmonella enteritidis and aerobic plate counts in chicken stored in air and modified atmosphere. AB - The objective of this work was to compare between and within sample differences in aerobic plate counts (APC) and Salmonella in chicken held at abusive temperatures under air and modified atmosphere (MA). Three independent samples and three subsamples of ground raw chicken meat were inoculated with a nalidixic acid-resistant Salmonella enteritidis var. Rochester, packaged in barrier films containing air or 75% CO2, 20% N2, and 5% O2, and stored at 13 and 27 degrees C for 120 h. Samples were quantitatively enumerated for APC and S. enteritidis colony forming units (cfu/g). Gompertz function parameters for microbial growth in each sample and subsample were statistically compared in order to determine if within sample variation was different to between sample variation. At 13 degrees C, APC organisms averaged 1.27 log units lower in the MA compared to air while Salmonella counts averaged 1.44 log units higher. At 27 degrees C APC averaged 0.46 log units lower in the MA compared to air while Salmonella averaged 0.30 log units lower. The data fit the Gompertz function such that no systematic deviations from the curves were detected and the confidence bands were relatively narrow. Except for initial microbial load, there were no significant differences in variance of Gompertz parameters between the subsamples and the independent samples. This indicates that samples from different chickens with the same initial APC can be expected to be as similar in growth patterns and final counts as subsamples from the same chicken. PMID- 8466813 TI - Yeasts associated with Vienna sausage packaging. AB - A total of 123 representative yeast isolates from a previous study of a Vienna sausage processing plant were identified according to conventional methods and long-chain fatty acid analyses. The most prevalent isolates belonged to the genera Candida and Debaryomyces. Other genera encountered were Rhodotorula, Yarrowia, Pichia, Galactomyces, Cryptococcus, Trichosporon and Torulaspora. PMID- 8466814 TI - Development and evaluation of a novel sterilizer with rotary vibrators. AB - A novel steam-air sterilizer with rotary vibrators was developed with the aim of promoting heat transfer and the effective sterilization of foods. To evaluate the effects of the sterilizer, experiments to examine heat transfer and sterilization tests were carried out. In the experiments to examine heat transfer, heat penetration factors of sterilizer with vibration, j and fh values, were 1.70 and 1.50, respectively, while those of sterilizer without vibration were 1.83 and 2.32, respectively. In the sterilization with vibration, no surviving cells were detected after 3 min, whereas 7 min were required for sterilization without vibration. The rate of the amino carbonyl reaction was repressed by heat treatment with vibration. PMID- 8466815 TI - Microbial flora of frozen tail meat from captive Nile crocodiles (Crocodylus niloticus). AB - Frozen tail meat samples from nine Nile crocodiles (Crocodylus niloticus) were evaluated for microbial numbers and types. Microbial analyses yielded a mean aerobic plate count (APC, 30 degrees C) of 4.86 log cfu/g, a mean coliform count (TC, 37 degrees C) of 3.77 log cfu/g and a mean faecal coliform count (FC, 44 degrees C) of 3.40 log cfu/g. Salmonella was isolated from three samples, and beta-haemolytic streptococci from two samples. Yersinia, Aeromonas, Staphylococcus aureus and Bacillus cereus were not isolated. Typical bacterial genera recovered included Flavobacterium, Pseudomonas, Acinetobacter, Enterobacter, Moraxella, Micrococcus, Staphylococcus and Streptococcus. PMID- 8466816 TI - Novel mechanism for the CAMP reaction between Listeria monocytogenes and Corynebacterium equi. AB - The synergistic hemolytic reaction between Listeria monocytogenes, Staphylococcus aureus and Corynebacterium equi on blood agar plates was explored using a modified test-tube assay. A synergistic lysis of sheep red blood cells was observed with L. monocytogenes and either S. aureus or C. equi, using crude extracts. Synergism was also found with L. monocytogenes and purified cholesterol oxidase from Pseudomonas fluorescens and Brevibacterium brevi. Crude extracts of S. aureus sensitized sheep red blood cells to subsequent lysis with either L. monocytogenes or C. equi. The interaction between L. monocytogenes and C. equi apparently did not involve a pre-sensitization step; simultaneous exposure of sheep red blood cells to the two extracts was required. A number of strains of L. monocytogenes gave positive synergistic reactions with cholesterol oxidase, suggesting that this reaction may be more useful than the CAMP test with C. equi for identifying L. monocytogenes. These results suggest that a novel synergistic reaction may be taking place, possibly involving the listeriolysin O, or one or both of the phospholipases from L. monocytogenes. PMID- 8466817 TI - Accident & emergency nursing: why are we waiting? PMID- 8466818 TI - Health and safety: assessing the risks. PMID- 8466819 TI - Avoiding the risk of needlestick injuries. AB - It is dangerous not to recap used needles, yet it can be equally dangerous to recap them. For each of us in the health sector, the prevention of needlestick injury (NSI) should be an everyday objective. This article discusses the risks associated with NSIs and examines whether current recommendations are being ignored. PMID- 8466820 TI - Farewell to a special nurse. PMID- 8466821 TI - Meeting the health needs of gypsies. PMID- 8466822 TI - Ethics: nursing care of gay and lesbian patients. AB - Work currently being undertaken by the Royal College of Nursing's Lesbian and Gay Nursing Issues Working Party has revealed evidence of prejudice towards, and discrimination against, lesbian and gay patients by members of the nursing and medical professions. In addition, there are instances when the specific nursing needs of this population have not been met due to lack of knowledge on the part of practitioners. Lesbians and gay men who have mental health problems are particularly vulnerable to abuse from homophobic health care workers. Lesbian and gay teenagers are even more vulnerable, and they run the added risk of being labelled mentally ill because of behaviour which is considered socially undesirable. This article discusses the research evidence and highlights the need for further investigation into providing appropriate and acceptable services to these patients. PMID- 8466823 TI - Nursing, HIV & AIDS: AVERT funded project. AB - October 1991 saw the start of a two-year national investigation into the nursing care and treatment of people with HIV/AIDS. The project is based in the Daphne Heald Research Unit at the Royal College of Nursing and is funded by the AIDS Education and Research Trust (AVERT). The aim is to gather information on current approaches to nursing care and treatment at a number of centres around the country, and to identify some of the main issues that are important to nurses undertaking this work. This article is based on preliminary reading and discussions with nurses, and makes some general points about the nursing profession's response to HIV/AIDS. PMID- 8466824 TI - Alternative therapies: a new holistic science. PMID- 8466825 TI - Uninhibited introductions. PMID- 8466826 TI - Standards of care: whistle down the drain. PMID- 8466827 TI - Information technology: what will computers do for me? PMID- 8466829 TI - HIV surveys should be treated with caution. PMID- 8466828 TI - NHS reforms: stop corporate blandishment. PMID- 8466830 TI - Tributes flood in for Richard Wells--'a very special man'. PMID- 8466831 TI - Occupational stress in head teachers: a national UK study. AB - This study assessed occupational stress amongst 2,638 head teachers of primary and secondary schools, together with principals/directors of further and higher education establishments, throughout the United Kingdom. Data were collected on personal/job demographics, sources of job stress, mental health, job satisfaction and coping strategies. These data were analysed by SPSS-X, producing univariate, bivariate and multivariate techniques. It was found that as we moved from the further/higher education level to secondary to primary sectors, the levels of job dissatisfaction and mental ill health rose. In addition, it was found that, with the exception of primary schools, female head teachers in secondary and FHE seem to be suffering significantly greater job dissatisfaction than their male counterparts, although this does not translate itself into mental ill health. Male head teachers, on the other hand, seem to suffer more mental ill health than their female counterparts. And finally, the two main sources of occupational stress that appear in many of the multivariate analyses as predictors of job dissatisfaction and mental ill health are 'work overload' and 'handling relationships with staff'. The implications of all these findings are discussed in detail. PMID- 8466832 TI - Effective use of pictures as extra stimulus prompts. AB - Past research on learning single words in the presence of pictures has suggested that the pictures can function as a blocking element which inhibits the development of an association between the written word and its spoken response. The purpose of this study was to investigate whether the extra stimulus pictorial prompts can be arranged in a different manner which does not inhibit the learning of the words. Three presentation techniques were investigated using samples (N = 12) of kindergarten children: matching, matching with the fading of the pictorial stimulus prompts, and feedback cueing. The results showed that, in general, the best learning occurred in the absence of the pictorial prompts, that is, when the words were presented alone. In the case of the feedback cueing condition, however, this technique neutralised the blocking effect of the pictures and the performance was as good as the word-alone condition. PMID- 8466833 TI - What do inventories of students' learning processes really measure? A theoretical review and clarification. AB - Research into student learning has been based on two main theoretical sources: information processing (IP), and contextually based work on students' approaches to learning (SAL). The cross-fertilisation has been valuable, but it has led to ambiguities and misunderstandings, evident in the recent literature, about constructs, methodology, and of particular concern here, the development and interpretation of inventories of learning/study processes. The basic issue revolves around a conception of student learning as taking place within-the student, as IP models appear to assume, or within-the-teaching/learning-context, as the SAL tradition emphasises. It is suggested that student learning is best construed within a teaching/learning context that functions as an 'open system', a model that brings some clarity to the use and interpretation of study process inventories, and that locates their value in yielding functionally useful data to researchers, teachers, and staff developers. PMID- 8466834 TI - A critique of research on cognition and cognitive processes. AB - In this article it is pointed out that there exists a methodological contradiction in most research on cognition and cognitive processes, which makes such research invalid in the strongest meaning of the term. When the aim is to study cognitive processes very often the researcher uses attributes of the learning material to be the standard or the template against which any outcome of the subjects can be analysed and made the ground for inferences about cognition and cognitive processes. This way of doing research is considered to be based on false theoretical assumptions and also proven invalid by a number of empirical studies. It is suggested in the article that the researcher must distinguish between an educational and a cognitive perspective and avoid mixing them in order to carry out successfully research on cognitive processes. PMID- 8466835 TI - Relations between children's playground and classroom behaviour. AB - In this within-subjects design field experiment children's behaviour in the playground was charted as a function of gender and time in the classroom immediately preceding playtime. Playground behaviour was also related to post recess classroom behaviour. Twenty-three 9-year-old children were observed for 14 weeks. Classroom behaviour (i.e., task relevant behaviour on standardised seat work immediately before and after playtime) and playground behaviour (i.e., social and non-social exercise and sedentary behaviour) were observed. Time in classroom before playtime was manipulated so that there was a shorter and a longer confinement period. Results indicated that children were less attentive to seat work as a function of time and that longer confinement resulted in more exercise for boys and more social sedentary behaviour for girls. Social behaviour at playtime and post-playtime attention to seat work were significantly related. Results are discussed in terms of Novelty Theory. PMID- 8466836 TI - Vygotsky and Papert: social-cognitive interactions within Logo environments. AB - The purpose of this study was to examine the effects of co-operative and individualised Logo environments on creativity and interpersonal relationships regarding academic recognition and social acceptance. Participants were 83 students who studied in three eighth grade classrooms: one was exposed to a co operative Logo environment (N = 30), the other to an individualised Logo environment (N = 24), and the third served as a non-treatment control group (N = 29). Results showed that students in the cooperative Logo environment outperformed their counterparts in the other two groups on certain measures of creativity (figurative-originality, verbal-flexibility, and verbal-originality). In addition, the co-operative Logo group developed more positive interpersonal relationships than the students in the other two settings. The results are discussed from three perspectives: the social-cognitive approach emphasising the roles of co-operation and metacognition in developing advanced thinking skills; the educational-technology viewpoint demonstrating the potential use of computers; and the pedagogical view pointing out the implications of the study to school situations and heterogeneous classrooms. PMID- 8466837 TI - Tooth and nail syndrome: genetic, clinical and dermatoglyphic findings: case report. PMID- 8466839 TI - Pediatric dentistry a metaphor for life: the third option. PMID- 8466838 TI - Anomalies associated with hypodontia of the permanent lateral incisor and second premolar. AB - Apart from the molars the most commonly congenitally absent tooth is the second premolar followed by the permanent lateral incisor. From a total of 5127 patients, congenital absence of the permanent lateral incisor occurred with a frequency of 2.2 per cent and absence of the second premolar with a frequency of 3.4 per cent. In association with hypodontia of these teeth other dental anomalies were observed. Absence of other teeth was observed as the most likely associated dental anomaly. Other anomalies recorded included disturbances in spacing of the dentition, and problems associated with tooth eruption and exfoliation. PMID- 8466840 TI - Improving profitability in a fee for service pediatric dental private practice through internal marketing. AB - To maximize your internal marketing, emphasize quality, services, and services added in your office. Your increased understanding of the needs and wants of your patients will be financially rewarding and gratifying. PMID- 8466841 TI - Children's behavior in emergency and non-emergency dental situations. AB - This study evaluated children's behavior during emergency and non-emergency visits to the dentist. Three methods were used to evaluate behavior: 1) the Palmar Sweat Index, 2) the Taylor Manifest Anxiety Scale, and 3) the Frankl Behavior Scale. Forty children, 6-12 years of age, were seen in a pediatric dental clinic. All children had no previous dental experiences. Twenty patients were seen for new patient examinations and twenty patients had emergency examinations and treatment. This study showed that children exhibit equal levels of stress whether for a screening appointment or an emergency visit. The Palmar Sweat Index has the potential of being a viable evaluation for detecting non verbally expressed anxiety. PMID- 8466842 TI - An investigation of accessory foramina in furcation areas of human primary molars: Part 1. SEM observations of frequency, size and location of accessory foramina in the internal and external furcation areas. AB - Although the existence of accessory foramina in the furcation area and roots of permanent teeth has been demonstrated, the presence of accessory foramina in furcation areas of primary molars is less certain. This investigation was conducted to determine the presence or absence of accessory foramina in the furcation areas of human primary molars using the scanning electron microscope (SEM). Twenty extracted, carious and noncarious human primary molars were placed in fixative and then mounted in a hard tissue cutting machine: ten teeth were cut transversely 2.0mm coronal to the floor of the pulpal chamber and ten teeth were cut transversely 2.0mm apical to the external furcation. Both the internal and external furcation surfaces of these sectioned molars were debrided with sodium hypochlorite/hydrogen peroxide solutions to remove organic materials, which might obscure visibility of possible foramina and then rinsed in water and dried. The tissues were then prepared for and examined by SEM. Twenty percent of the molars examined by SEM on the internal furcation surface and 50% of the molars examined by SEM on the external furcation surface demonstrated accessory foramina. PMID- 8466844 TI - Chemical analysis of a dens invaginatus by SEM microanalyses. AB - A patient with a supernumerary right maxillary lateral incisor with dens invaginatus presented. After extraction, the invaginated area of the tooth as well as another of similar ages but with normal hard tissues, were prepared for scanning electron microscopic observation. Outer and invaginated enamels were identified the latter showing more density. Chemical analysis by the scanning microanalyses revealed differences in mineral contents between: a) the external and cut surface of the outer and the invaginated enamel, and b) the external and cut surface of the normal tooth. The outer and invaginated enamels are quite different concerning the quantity and quality of minerals, the latter having no magnesium at all. Magnesium was also non existent in the dentin. PMID- 8466843 TI - An investigation of accessory canals in furcation areas of human primary molars: Part 2. Latex perfusion studies of the internal and external furcation areas to demonstrate accessory canals. AB - Four classes of accessory canals: "true," "blind," "looping" and "enclosed" canals have been suggested to exist in furcation areas of primary teeth. Although the existence of accessory canals in the furcation areas and roots of permanent teeth has been demonstrated, their presence in furcation areas of primary teeth is uncertain. This investigation was conducted to determine the presence or absence of accessory canals in the furcation areas of human primary molars using a variety of latex perfusion techniques. Twenty extracted, noncarious human primary molars were placed in fixative and then sectioned on a hard tissue cutting machine: ten teeth were cut transversely 2.0 mm coronal to the floor of the pulpal chamber and ten teeth were cut transversely 2.0 mm apical to the external furcation area. The internal and external furcation surfaces of these sectioned molars were debrided with sodium hypochlorite/hydrogen peroxide solutions, rinsed in water and dried to remove organic materials, which might obscure the existence of possible canals. Twenty of these extracted teeth were examined by SEM to detect the possible presence of accessory foramina in the internal and external furcation areas (Part 1). Twenty percent of the molars examined by SEM on the IFA and 50 percent of the molars examined by SEM on the EFA exhibited accessory foramina. Twenty molars were perfused with low viscosity latex using vacuum [negative] pressure (10 molars) and positive pressure (10 molars) to detect the possible existence of the patency and the extent of such accessory canals in the internal and external furcation areas (Part 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466845 TI - Effect of fluoridated gels on a light-cured glass ionomer cement: an SEM study. AB - This SEM study evaluated the micromorphological effect of a 1.23% acidulated phosphate fluoride gel (Oral-B) (APF) and a neutral 1.1% sodium fluoride gel (Thera-Flur) (Colgate-Hoyt) on the surface of a light-cured glass ionomer cement (Fuji II LC) with or without a protective surface glazing. Glass ionomer (GI) cylinders (area 6.69 mm) were prepared and divided into six groups of 10 specimens each: Group 1: GI; Group 2: GI + APF gel for 4 minutes; Group 3: GI + glaze; Group 4: GI, glaze, APF for 4 minutes; Group 5: GI, neutral fluoride for 4 minutes; Group 6: GI, glaze, neutral fluoride for 4 minutes. The glass ionomer was handled according to manufacturer's instructions, except for the groups using the glaze after light-curing the GI. The glaze resin (Ketac-Glaze) was painted with a brush over the GI surface and cured with visible light (Demetron) for 30 seconds. The fluoride gels were left in contact with the surface for 4 minutes, rinsed and dried. All specimens were then mounted on aluminum stubs, coated and evaluated under the SEM. The results indicated that the APF gel etches the GI surface considerably and that the glaze protects the GI from the APF gel. The neutral fluoride gel had no significant effect on the GI surface with or without the glaze application. PMID- 8466846 TI - Incidence of malocclusion in asthmatic children. AB - This study examined the relationship of a compromised airway in asthmatic children, i.e. mouthbreathing, and the effect that the airway compromise has on occlusal and facial characteristic. The study consisted of sixty-four children of both sexes, ranging in age from three to sixteen years. Thirty-two subjects were from the pulmonary and allergy clinic of the Floating Hospital, New England Medical Center, who were present for follow-up and/or treatment of asthma. Thirty two randomly selected children were selected from the pediatric clinic in Tufts University School of Dental Medicine to serve as controls. The two groups were equally balanced according to age, sex and race. A statistically significant relationship was found between the frequency of crossbites and the frequency of mouth breathing. Additionally, a statistically significant relationship was found between the frequency of crossbites and the facial type in the experimental group. The frequency of crossbites appears to be related to abnormal facial types. PMID- 8466847 TI - Supernumerary teeth removal and orthodontic tooth repositioning: a case report. AB - A case is presented of a 12-year-old, black male, who had a full permanent dentition except for retaining the two maxillary primary central incisors. A radiographic examination revealed the presence of two supernumerary teeth interfering with the eruption of the permanent central incisors. Space was orthodontically created for the permanent central incisors, the primary central incisors and supernumerary teeth were removed, and the permanent central incisors were orthodontically brought into proper alignment. PMID- 8466848 TI - Papillon Lefevre syndrome: treatment of two cases with a clinical microbiological and histopathological investigation. AB - Papillon Lefevre syndrome is presented in the cases of two female patients of the ages of 7 and 9, who exhibited all typical symptoms of the disease. Microbiological and histopathological studies were done and treatment provided. Actinobacillus actinomycetemcomitans, which is suspected as a pathogenic factor in the disease was identified as well as some other gram negative microorganisms and an antibiogram was performed in which amoxycillin plus clavulanic acid was most effective. Histopathological investigation also confirmed the presence of gram negative bacteria. Granular cell infiltration was predominant in the surface epithelium. Prosthetic appliances were provided for the patients after mechanical and chemical plaque control. In addition to this, antibiotics (amoxycillin plus clavulanic acid) were prescribed every six months. No tooth loss was observed in both patients after more than two years follow-up period. At the moment only one patient is under review and because she is uncooperative, mild periodontal inflammation is still present around the teeth which erupted before the antibiotic regime, but not in the other teeth. PMID- 8466849 TI - Tumor cell proliferation and motility estimates are prognostic factors in malignant melanoma. AB - Metastatic spread of solid tumors depends on a complex metastatic cascade. Metastatic tumor cells must therefore express a variety of biological properties including the ability to proliferate and the ability to migrate. In the present study, the prognostic significance of both parameters was investigated in 184 cases of malignant melanoma of the skin. Proliferative activity was assessed by mitotic counts, the degree of cell motility was estimated by comparing the histological pattern of the tumor with patterns obtained by computer simulations with predefined values of cell motility. Follow up of surviving patients was at least 5 years. Statistical analysis was done using classification and regression tree (CART) analysis combining mitotic counts and motility estimates. As far as overall survival was concerned, mitotic counts were the most significant variable separating one group of patients with mitotic counts < 17/mm2 and a 5-year survival rate of 82% and a group with mitotic counts > or = 17/mm2 and a 5-year survival rate of 52%. Within the group with low mitotic counts, motility estimates found a subgroup of patients with a coefficient of motility > or = 126, which had a 5-year survival rate of 55% similar to those patients with high mitotic counts. Corresponding results were obtained in the assessment of metastasis-free interval. The data show that not only proliferation as assessed by mitotic counts, but also estimates of tumor cell motility based on image analysis and computer simulations provide prognostic information in primary malignant melanoma of the skin. PMID- 8466850 TI - A constant flux system using the 'magnetic cell separator' (MACS) for highly efficient T-cell depletion. AB - A method for highly efficient T-cell depletion using a 'Magnetic Cell Separator' (MACS) is described. T-lymphocytes were depleted from peripheral blood samples of 37 patients with chronic lymphocytic leukemia (CLL). The flow speed in the MACS column was adjusted by a syringe-driver allowing a constant flow speed of about 100 microliters/min. The mean content of T-cells after depletion was 0.17% (S.D. +/- 0.27). The effectiveness of depletion was calculated to a mean 93.7%. There was no correlation between the proportion of CD3-positive cells before and after depletion. PMID- 8466851 TI - Detection of false DNA aneuploidy and false DNA multiploidy in flow cytometric DNA analysis. AB - Although false DNA aneuploid peaks have previously been described in normal tissue, criteria for distinguishing them from 'true' near-diploid peaks have not been established. Normal thyroid (n = 4) and kidney (n = 1) tissue were allowed to autolyze over a fixed period of time and DNA content was analyzed by flow cytometry (FCM). Autolysis was associated with the development of distinct separate G0/G1 peaks which had low DNA indices (1.09-1.18) and showed decreased forward light scatter (FSC) when compared to fresh tissue. Using DNA content and FSC measurements similar false DNA aneuploid peaks were identified in 29/94 surgical specimens. These cases included both benign and malignant lesions from thyroid (n = 63) with the remaining 31 neoplastic cases being from breast (16), lymphoma (8), sarcoma (4), lung (2) and uterine (1) tissue. In addition, false DNA multiploidy was identified. None of these cases showed histological evidence of necrosis. In a parallel comparison study using image cytometry (ICM) on the thyroid nodules, the presence of false DNA aneuploidy was supported. Investigators should routinely employ quality control criteria to identify possible cases of false DNA aneuploidy when measuring DNA content using FCM. PMID- 8466852 TI - Spectral analysis of cervical cells using the discrete Fourier transform. AB - This paper contains results from a preliminary study of spectral analysis techniques applied to the classification of cervical cells from routinely prepared Papanicolaou cervical smears. Experiments were conducted using a subset of 110 normals and 110 dyskaryotic single cell images randomly selected from a larger cell image data base. An assessment was made of the contribution of different regions within a cell image to the frequency spectrum. Three image sets were used, the original image itself plus two derived from it. In the first derived set, only nuclear size and shape were used. In the second set nuclear morphology and texture were included. Nuclear masking was performed using an interactive segmentation procedure. The discrete Fourier transform was applied to each image in the three image sets and classification experiments were performed using 80 features derived from the frequency spectra. An optimum set of features was selected for each experiment by canonical analysis. Good classification results were obtained when features extracted solely from nuclear shape were used. The inclusion of information relating to nuclear texture improved the results. However, inclusion of the extra nuclear region degraded the classifier's ability to discriminate between cell groups. PMID- 8466853 TI - Enhanced expression of the human multidrug resistance 1 gene in response to UV light irradiation. AB - The multidrug resistance 1 (MDR1) gene encodes a M(r) 170,000 membrane glycoprotein termed P-glycoprotein, which catalyzes the energy-dependent efflux of multiple anticancer agents. We investigated the activation of the MDR1 gene promoter by UV light irradiation in human cancer KB cells after both transient and stable transfection assays of the MDR1 promoter fused to the chloramphenicol acetyltransferase (CAT) gene. Following exposure to UV irradiation, CAT gene expression was about 20-fold increased. A series of promoter dissection analyses showed that two elements extending from -136 to -76 of the 5' flanking sequence and from +1 to +121 of the sequence downstream from the initiation site were required for the stress induction of MDR1 promoter activity. Gel shift assays showed that the specific DNA binding activities of the transacting protein to the MDR1 promoter were augmented in nuclear extracts from the cells treated with UV irradiation. A DNA sequence, an inverted CCAAT box, was identified that specifically bound to this protein, and mutation of this sequence abolished the binding of this protein. Two guanines in the inverted CCAAT box were found to be critical, as methylation of these guanines abrogated the binding. Nuclear run-on assay demonstrated that the transcription level was increased about 5-fold. These results suggest that the activation of the MDR1 promoter may result from transcriptional rather than posttranscriptional events. These studies will provide the basis for understanding the regulatory mechanism for appearance of the drug-resistant phenotype during cancer chemotherapy. PMID- 8466854 TI - Phorbol ester-induced monocytic differentiation is associated with G2 delay and down-regulation of cdc25 expression. AB - Treatment of human U-937 myeloid leukemia cells with 12-O-tetradecanoylphorbol-13 acetate (TPA) is associated with growth arrest and induction of monocytic differentiation. The present results demonstrate that exposure of G1- or S phase enriched U-937 cells to TPA was associated with delayed transition through G2-M and then exit from the cell cycle in the subsequent G0-G1 phase. In contrast, G2 M cells treated with TPA progressed through G1-S, were delayed in the next G2-M phase, and then entered a nonproliferative G0-G1 state. The effects of TPA on expression of cell cycle control genes demonstrated down-regulation of the cdc25 mitotic inducer during S-G2 progression. In order to investigate the role of cdc25 in the control of cell cycle progression, U-937 cells were stably transfected with an antisense cdc25 construct under control of a metallothionein inducible promoter. Expression of this construct in G1 phase cells was associated with a significant delay in transition through S and G2-M phase. Similar results were obtained when G1 phase cells were incubated with a 14-base pair antisense cdc25 oligomer. Taken together, these results indicate that the cdc25 gene product is functionally associated with S-G2 transition of proliferating myeloid leukemia cells and that down-regulation of this gene by TPA is associated with G2 M delay. PMID- 8466855 TI - Predominant expression of nPKC eta, a Ca(2+)-independent isoform of protein kinase C in epithelial tissues, in association with epithelial differentiation. AB - Of the nine known members of the protein kinase C (PKC) family, we found that novel (n-) PKC eta, a newly isolated Ca(2+)-independent isoform, was expressed at the highest level in the epidermis of mouse skin and epithelia of the digestive and respiratory tracts including the tongue, esophagus, forestomach, glandular stomach, intestine, colon, trachea, and bronchus. Expression of nPKC eta mRNA in these epithelial tissues was 3-10 times that in the brain and was especially high in squamous epithelium. Two other PKC isoforms, conventional (c-) PKC alpha and nPKC delta, were also expressed in these epithelial tissues, but no cPKC gamma was detected. In situ hybridization and immunohistochemical analyses demonstrated the localization of nPKC eta in suprabasal layers of the skin, tongue, esophagus, and forestomach. In the intestine, it was expressed in the epithelial cells of villi, but not of crypts. In the lung, only bronchial epithelium expressed nPKC eta. The localization of nPKC eta in differentiating or differentiated epithelial cells, rather than in proliferating basal cells, suggests the involvement of nPKC eta in epithelial differentiation. PMID- 8466856 TI - Altered growth and spontaneous transformation of cells cultured from v-jun transgenic mice recapitulate wound-induced multistage tumorigenesis. AB - H-2K/v-jun transgenic mice develop sarcomas at sites of wounding via a multistep process characterized by discrete pathological stages. To study this progression in vitro, cells from different stages of tumorigenesis were cultured and examined for their growth properties. The results show that whereas transgenic fibroblasts do not manifest enhanced proliferative potential in vivo in the absence of wounding, they do show obvious proliferative advantage relative to nontransgenic fibroblasts in vitro, including the capacity for indefinite growth. In addition, relative to nontransgenic fibroblasts, transgenic cells show altered sensitivity to platelet-derived growth factor and tumor necrosis factor alpha, both of which are known to be mobilized during wounding. No obvious differences in growth potential are observed between transgenic fibroblasts and cells cultured from wound-induced premalignant lesions, and confluent cultures of both cell populations give rise to spontaneous foci of transformed myogenic and nonmyogenic cells that resemble those of late-stage malignant wound sarcomas. Relative to transgenic fibroblast cultures, however, premalignant lesion cultures segregate transformed cells at a greater frequency and after shorter intervals of in vitro growth. The results suggest that wound-induced multistage tumorigenesis can be recapitulated in vitro and that cells cultured from different stages of tumorigenesis retain biological properties that reflect the pathological stage from which they are derived. PMID- 8466857 TI - Transforming growth factor beta 1 can induce estrogen-independent tumorigenicity of human breast cancer cells in athymic mice. AB - We have examined the effect of transforming growth factor beta 1 (TGF-beta 1) overexpression in human breast cancer cell tumorigenicity in athymic mice. Estrogen-dependent MCF-7 cells were stably transfected with pSVTGF beta 1. A clone was isolated which overexpressed TGF-beta 1 mRNA and secreted > 10-fold more TGF-beta activity into the tissue culture medium. Similar to the parent line, the MCF-7/TGF-beta 1 cells were relatively insensitive to exogenous TGF beta 1 and exhibited low levels of TGF-beta receptors. Clonogenicity in soft agarose, doubling time, morphology, and sensitivity to 17 beta-estradiol and the antiestrogen tamoxifen were not altered in the transfected cells. Inoculation s.c. of MCF-7/TGF-beta 1 cells in ovariectomized nude mice resulted in 100% tumor formation which was totally abrogated by i.p. administration of the neutralizing anti-TGF-beta 2G7 IgG2B. The parent cells formed tumors only after estrogen supplementation. By immunohistochemistry, higher levels of TGF-beta 1 protein were detected in MCF-7/TGF-beta 1 tumors than in estrogen-induced parent MCF-7 tumors. Administration of 1 microgram TGF-beta 1 i.p. daily for 3 weeks after tumor cell inoculation transiently supported estrogen-independent growth of parent MCF-7 tumors in castrated nude mice. These data indicate that overexpression of TGF-beta 1 in human breast cancer cells can contribute to their escape from hormone dependence. PMID- 8466858 TI - Regulation of fat and muscle development by transforming growth factor alpha in transgenic mice and in cultured cells. AB - Transgenic mice overexpressing transforming growth factor alpha (TGF-alpha) under control of the metallothionein promoter had, on average, 20% reductions in body and carcass weights compared to nontransgenic littermates. This loss resulted from significant decreases in the comparative weights of bone, muscle, and especially fat. Transgenic epididymal fat pads were reduced by 40-80%, and total body fat content by 50%, relative to control animals. Distal hindlimb muscle weights were 20% below normal, and other skeletal muscles were visibly smaller in size. Weight reductions were accompanied by decreases in the cellularity of transgenic fat pads and muscles and by decreases in the number and area of striated muscle fibers. These findings were not obviously attributable to differences in metabolic rates since transgenic and control mice displayed similar levels of energy expenditure per unit lean body mass. The effects of TGF alpha on the development of these tissues could be mimicked in culture for fat but not muscle. Thus, TGF-alpha did not inhibit the differentiation of the mouse skeletal myoblast cell line C2C12 as evidenced by the expression of muscle specific actin and fusion to form multinucleated myotubes. However, TGF-alpha repressed the differentiation of the preadipocyte cell line 3T3-F442A in a dose dependent and reversible manner as judged by morphological conversion and diminished expression of mRNAs encoding the adipocyte-specific markers adipsin and glycerophosphate dehydrogenase. This repression, which occurred without marked stimulation of proliferation, was incomplete even in the presence of high concentrations of growth factor. Despite its effects on adipose development, introduction of the metallothionein-TGF-alpha transgene into the ob/ob genetic background did not suppress the marked obesity characteristic of this mutation. Finally, endogenous TGF-alpha epidermal growth factor receptor mRNAs were detected in normal adipose tissue, suggesting that regulation of adipogenesis by this growth factor may be physiological. PMID- 8466859 TI - Glucocorticoids reversibly arrest rat hepatoma cell growth by inducing an early G1 block in cell cycle progression. AB - We have previously documented that glucocorticoids suppress the proliferation of BDS1 hepatoma cells, a rat epithelial tumor cell line derived from minimal deviation Reuber H35 hepatoma cells. Flow cytometry demonstrated that, after treatment with the synthetic glucocorticoid dexamethasone, the growth of an asynchronous population of BDS1 cells was arrested within one cell cycle which resulted in an accumulation of cells with a G1-G0-like DNA content. Consistent with a glucocorticoid-induced block early in the G1 phase of the cell cycle, propidium iodide flow cytometry revealed that addition of dexamethasone up to 2 h after release from contact inhibition prevented BDS1 hepatoma cells from entering S phase, whereas dexamethasone treatment after 2 h had no effect on the entry of cells into S phase. Moreover, dexamethasone treatment did not prevent BDS1 cells from entering S phase after release from synchronization at the G1-S boundary by a double thymidine block. Analysis of DNA content, [3H]-thymidine incorporation, and autoradiography of [3H]-thymidine-labeled nuclei revealed that, after release from dexamethasone, BDS1 cells synchronously reinitiated cell cycle progression and entered S phase 8 h after hormone withdrawal. Northern blot analysis demonstrated that the level of transcripts encoding the G1 marker genes CYL-1 and CYL-2 G1 cyclins peaked 4 h after dexamethasone withdrawal. Dexamethasone induced a 20-fold increase in the level of c-jun mRNA which was reversed after hormone withdrawal, whereas expression of c-fos transcripts remained at a low level during the time course of hormone treatment and withdrawal. Transient transfections with a collagenase-chloramphenicol acetyltransferase reporter gene showed that dexamethasone inhibited 12-O-tetradecanoylphorbol-13-acetate inducible, but not basal, AP-1 transcription factor activity. Our results demonstrate that glucocorticoids reversibly induce an early G1 block in cell cycle progression of an epithelial tumor cell line that occurs with a coordinate elevation in the expression of c-jun transcripts. PMID- 8466860 TI - Schwann cell lineage-specific neu (erbB-2) gene expression in the developing rat nervous system. AB - Initiation of oncogenesis in the immature peripheral nervous system (PNS) of rats by the DNA-reactive carcinogen N-ethyl-N-nitrosourea (EtNU) involves a specific T:A-->A:T transversion mutation at nucleotide 2012 of the neu (erbB-2) receptor tyrosine kinase gene in cells of the Schwann cell lineage. Although this mutation is invariably detected in the resulting malignant schwannomas, it is not found in EtNU-induced tumors of the central nervous system (CNS). We have evaluated expression of the neu gene in the PNS and CNS as a function of developmental stage. Cellular levels of neu mRNA and gp185neu were analyzed in the trigeminal and sciatic nerve and in brain, using a quantitative reverse transcription polymerase chain reaction, in situ hybridization, immunocytochemistry, and fluorescence-activated cell sorting. In the PNS, expression of the neu gene is restricted to cells of the Schwann cell lineage and markedly exceeds expression in the CNS from prenatal day 20 onward. In trigeminal Schwann cells, neu mRNA is most abundant (2.8 x 10(7) copies/micrograms of RNA) on postnatal day 1, coincident with both the end of maximum mitotic activity and the "developmental window" of highest sensitivity to malignant transformation by EtNU. The subsequent decrease of neu gene expression is accompanied by decreasing proliferative activity and the onset of myelination. The level of neu gene expression may thus be critical to proliferation versus differentiation decisions in the Schwann cell lineage. EtNU-induced mutation of the neu gene in proliferative Schwann cell precursors expressing gp185neu may abrogate their responsiveness to extracellular and/or intrinsic controls, resulting in sustained proliferative activity and malignant conversion. PMID- 8466861 TI - Interaction of a human Fc gamma RIIb1 (CD32) isoform with murine and human IgG subclasses. AB - A group of Fc receptor molecules, classified CD32, recognize the Fc moiety of IgG with low affinity. We report the isolation and identification of different hFc gamma RIIb cDNA clones, amongst which are cDNA clones encoding hFc gamma RIIb1 and hFc gamma RIIb2. Two hFc gamma RIIb1 encoding cDNA clones (pIP9 and pIP14) were isolated, which differed by three nucleotides, probably because of allelic variation. The nucleotide differences result in one amino acid change between the allelic hFc gamma RIIb1 variants. This substitution is located at amino acid position 11 of the cytoplasmic tail; a tyrosine in hFc gamma RIIb1 (clone pIP9) was replaced by an aspartic acid in clone pIP14 (encoding hFc gamma RIIb1*). A complication in studying ligand specificity of Fc receptors is the potential co expression of different classes, subclasses, or polymorphic forms of FcR on the same cell. We therefore used murine fibroblasts transfected with cDNA clone pIP14, encoding a hFc gamma RIIb1* isoform, as our model system. These fibroblasts were found to interact with erythrocytes sensitized with mIgG2a and mIgG2b in rosetting assays performed at 4 and 37 degrees C. Interestingly, hFc gamma RIIb1* transfectants bound mIgG1 sensitized erythrocytes only weakly at 4 degrees C, whereas profound binding was observed at 37 degrees C. The ligand specificity for human (h) IgG isotypes was found to be hlgG3 > or = hlgG1 > hlgG4 > hlgG2, as determined at 4 degrees C with hlgG dimeric complexes. However, when assayed at 37 degrees C, the binding of hlgG2 dimers increased significantly. Next, we evaluated whether these transfectants were capable of supporting anti CD3 induced T cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466862 TI - Cortical neurons selectively inhibit MHC class II induction in astrocytes but not in microglial cells. AB - Astrocytes have been shown to act as potent accessory cells for MHC class II restricted T cell responses in vitro after treatment with interferon-gamma. In contrast, even under conditions of severe central nervous system (CNS) inflammation, they seem to express little, if any, class II molecules in vivo. Thus the role of astroglial cells as accessory cells in immune responses in the CNS remains to be determined. We have studied neuron--glia interactions with respect to induction of MHC class II molecules. Surprisingly, in a co-culture system, viable neurons inhibited the induction of class II restriction elements on astrocytes. This effect was only observed when neurons had contact to astrocytes; neuron derived soluble factors alone were insufficient. Most interestingly, the suppressive effect of neurons on class II inducibility operated specifically on astrocytes, while microglial cells were left unaffected. PMID- 8466863 TI - Low frequencies of somatic mutation in two expressed V kappa genes: unequal distribution of mutation in 5' and 3' flanking regions. AB - Somatic mutation of antibody variable region genes is a hallmark of secondary responses. Most often the coexpressed VH and V kappa genes of a B cell mutate at nearly equal rates. We have previously identified hybridomas from two B cell clones that exhibited > 10-fold lower frequency of mutation in their expressed V kappa 12 or V kappa 1A genes relative to their coexpressed VH genes. To gain insight into the mechanism(s) responsible for this low frequency V kappa mutation, we determined the frequency of mutation in non-coding flanking DNA from multiple members of each clone. We find a low frequency of mutation in the 5' (4/700) and 3' (1/670) non-coding regions of the expressed V kappa 1A genes consistent with the low frequency of coding region mutation. In contrast, the distribution and frequency of mutation surrounding the expressed V kappa 12.37 gene are unusual. Among the six members of this clone there are 31 mutations 3' (31/2100 bp) and no mutations 5' (0/2010 bp) of the V kappa exon. This V kappa exon has acquired mutations that are intermediate in number to its flanking regions and are significantly skewed in distribution to the 3' end. None of the 31 3' mutations are shared by two or more members of this clone, indicating that they all occurred late in clonal expansion. These results raise the possibility that some V kappa genes may lack functional cis-regulatory elements which direct V kappa coding region mutation. PMID- 8466864 TI - The human I alpha 1 and I alpha 2 germline promoter elements: proximal positive and distal negative elements may regulate the tissue specific expression of C alpha 1 and C alpha 2 germline transcripts. AB - Treatment of human splenic B lymphocytes with the mitogen Branhamella catarrhalis (BC) and transforming growth factor-beta 1 (TGF-beta 1) induces expression of germline Ig C alpha transcripts and class switching to this isotype. To further characterize the molecular mechanism by which TGF-beta 1 and mitogenic signals regulate the expression of unrearranged C alpha 1 and C alpha 2 genes, we have characterized the promoter elements that are responsible for the transcriptional activation of their corresponding germline genes using transient expression assays. We report here that both in the I alpha 1 and the I alpha 2 regions, maximal phorbol myristate acetate (PMA) and TGF-beta 1 responsiveness of the promoters can be conferred by 327 bp spanning the transcription initiation sites and a previously identified phylogenetically conserved region. The expression of these 327 bp segments is not restricted to the B cell lineage since they are also active in the erythroleukemia cell line K562 as well as the B cell lines Raji and DG75. Mutational analyses have demonstrated the importance of sequences within the 327 bp segment that contain a putative cyclic AMP responsive element binding protein (CREB) binding site for TGF-beta 1 and PMA responsiveness and putative PU 1 and Sp1 binding sites for basal promoter activity. Upstream distal elements that could negatively modulate the expression of the I alpha 1 and I alpha 2 promoters, particularly in non-B cells, have been identified. Three such elements were mapped between positions -352 to -243, -627 to -516, and upstream of position -731 respectively. The influence of these elements presumably contributes to the B cell specific expression of the I alpha 1 and I alpha 2 promoters. The I alpha 1 and I alpha 2 promoters were found to be functionally indistinguishable from each other with respect to their basal level of expression, and their responsiveness to TGF-beta 1. PMID- 8466865 TI - Effects of isotype and Fc region on in vitro function of a mouse/human chimeric CD4 antibody. AB - Murine CD4 mAbs have shown potential for the treatment of allograft rejection and autoimmune disorders including rheumatoid arthritis. Clinical usefulness of the murine mAbs has been limited by immunogenicity and a short circulating half-life. Mouse/human chimeric antibodies have been constructed, composed of the variable region of M-T412 (a murine G2a mAb specific for the human CD4 molecule) and human G1 (cM-T412 G1) or G4 (cM-T412 G4) Fc regions. F(ab')2 and F(ab) fragments of the murine G2a and chimeric G1 mAbs were generated by enzymatic digestion. The chimeric mAbs and all fragments retained the avidity and specificity of the murine M-T412 and were evaluated in in vitro assays measuring Ig production by pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC), sIL 2R produced by phytohemagglutinin-stimulated PBMC, and proliferation in response to tetanus toxoid, CD3 mAb plus IL-2, and mixed lymphocyte response (MLR). When PBMC were stimulated with tetanus toxoid, 10 ng/ml of cM-T412 G1 inhibited proliferation by 90%, while neither the cM-T412 G4, M-T412 G2a, nor any mAb fragment produced > 65% inhibition, even at 1000-fold higher concentrations. A similar pattern of inhibition was observed in MLR assays. In contrast, the F(ab')2 fragment of the cM-T412 G1 was as effective as the whole antibody in inhibiting PWM-stimulated IgM synthesis and PBMC proliferation in response to stimulation by a CD3 mAb plus IL-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466866 TI - IL-4 regulates the morphology, cytoskeleton, and proliferation of human umbilical vein endothelial cells: relationship between vimentin and CD23. AB - Many of the vascular endothelial changes associated with inflammation can be induced in vitro by the cytokines tumour necrosis factor, IL-1, and IFN gamma. On the other hand, although IL-4 is a powerful mediator of leucocyte function, its influence on endothelial cells has not yet been fully determined. In this study the effect of IL-4 on human umbilical vein endothelial cells has been investigated. It is shown that IL-4 stimulates DNA synthesis over the first 24 h in culture, followed by dramatic alterations in endothelial cell morphology in which the cobblestone appearance of cells grown to confluence in medium changes to a monolayer composed of islands of tightly packed polygonal cells. The morphological changes induced by IL-4 were accompanied by a reorganization of the intracellular vimentin matrix from a diffuse pattern to a perinuclear concentration observed by staining with vimentin antibodies. Similar patterns of vimentin staining were also observed with an antibody to the low affinity IgE receptor (CD23) normally associated with IL-4 activation of B lymphocytes. Our results suggest that this represents cross reactivity between CD23 and vimentin rather than the appearance of CD23 in endothelial cells. Amino acid sequence comparison between CD23 and vimentin indicated significant homology between these two molecules, including a leucine zipper-like motif. Our results suggest that IL 4 may be an important regulator of endothelial cell morphology and function in inflammation. PMID- 8466867 TI - B-lineage cells in mu-transgenic scid mice proliferate in response to IL-7 but fail to show evidence of immunoglobulin light chain gene rearrangement. AB - The severe combined immunodeficiency (scid) mouse mutation impairs the recombination of Ig and TCR genes. Mice homozygous for this mutation (scid mice) lack pre-B, B, and T lymphocytes. Earlier we introduced a functionally rearranged mu-heavy chain gene into the scid mouse genome and found that this resulted in the development of pre-B cells in the bone marrow of these mice; however, sIgM+ B cells were not detected. We have now investigated the growth properties and rearrangement status of Ig genes in early B-lineage cells arising in mu transgenic scid mice. We find that the presence of a functional mu-transgene allows pro-B cells from these mice to proliferate in short-term culture with IL 7. Nevertheless, rearrangements of Ig light chain genes are not detected in the bone marrow of such mice. Furthermore, the frequency of rearrangement detected at the endogenous Ig heavy chain locus in scid pro-B and pre-B cells is reduced relative to that in wild-type cells. PMID- 8466868 TI - Complications and long-term results of the Nissen fundoplication. AB - The Nissen fundoplication is the operative therapy of choice in children with symptomatic gastroesophageal reflux. In recent years several reports on specific complications of the Nissen fundoplication have been published. This report summarizes the complications in 45 patients on whom a Nissen fundoplication was performed in our clinic between 1979 and 1989. 18 patients (40%) showed early or late complications. In 10 patients (22%) reoperation was necessary. However, at follow-up with a mean period of 4 1/2 years after surgery, 36 patients (92%) showed good results without any residual symptoms. The Nissen fundoplication had in our hands a rather high rate of complications. However, late results were excellent and our healing rate (92%) was higher than reported in other series with different techniques. PMID- 8466869 TI - Pancreaticobiliary long common channel syndrome and congenital anomalous dilatation of the choledochal duct--study of 46 patients. AB - Retrospectively evaluated clinical, radiological and anatomical findings of 46 patients with tubular or cystic dilated choledochal ducts indicate the following conclusion: Pathological stricture of the sphincter of Oddi system, including a hypertrophic and spastic portion of the sphincter choledochus inferior, called "narrow segment", raises the pressure in the choledochal duct to pathological levels and consequently causes a dilatation of the duct during a specific embryonic phase. Such a pathological sphincter of Oddi system develops if a long common channel persists as the result of a disturbance in the development of the distal choledochal and pancreatic duct. This statement contradicts the classical conception which assumes that a reflux of pancreatic juice into the choledochal duct causes ductal dilatation. Authors who are in favor of this conception propose that pancreatic juice causes weakness of the ductal wall, which may be dilated in the embryonic period. However, the findings of the series evaluated here show that dilatation of the duct may also originate without any reflux of pancreatic juice into the choledochal duct if a "narrow segment" exists above the junction of the pancreatic and choledochal ducts. For this reason, pancreatic juice reflux cannot be the condition sine qua non in the development of choledochal duct dilatation. Similarly the pathologic junction angulation can only be an optional factor in this autogenetic anomaly. With regard to a pathological sphincter of Oddi system the question arises whether a partial or complete myotomy of the muscular sphincter may be able to remedy the dilatation and avoid resection of the choledochal duct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466870 TI - Cystic fibrosis and portal hypertension interest of partial splenectomy. AB - Extra pulmonary complications can be major in patients suffering of cystic fibrosis who survive long enough without pulmonary problems. Hepatic cirrhosis is often present and is responsible for portal hypertension with splenomegaly, hypersplenism and esophageal varices. In six patients we have performed a partial splenectomy with conservation of the upper pole of the spleen vascularized by gastrosplenic omentum and its vessels. The post-operative complications (3 scar ruptures but no pulmonary decompensation) are not very important considering the benefits: Normal spleen according to clinical, ultrasonic examination and scintigraphy Correction of hypersplenism Diminution of esophageal varices Stability of hepatic functions. With a post-operative follow-up between 2.5 and 7 years, none of the patients had an increased risk of infection. This technique allows a good survival for those patients waiting for pulmonary transplantation. PMID- 8466871 TI - Use of the appendix to provide urinary continence. AB - We describe a technique used to provide urinary continence to a group of teenagers with neuropathic bladders. The technique gives continence to a urinary reservoir by utilising the appendix as a continent catheterisable conduit. Of the first five patients to have this procedure performed in this institute, four became fully continent. We feel that this procedure can be of great benefit to both children and adults with urinary incontinence. PMID- 8466872 TI - The relative proportions of type I and type II muscle fibers in the external sphincter ani muscle at different ages and stages of development--observations on the development of continence. AB - The external sphincter ani muscles were partially or completely removed from 11 fetuses, 3 infants, 2 children and 12 adults, none of whom had had anorectal disease and all of whom had died of diseases not affecting the anorectal organ of continence. Muscle fiber-typing was carried out. In the fetuses ages 26-40 weeks, we found a predominance of Type II (rapid) fibers. With increasing gestational age Type II fibers started to diminish along with a simultaneous increase in Type I (slow) fibers. At the same time, stromal restructuring took place. Three infants, ages 1, 2 and 10 months, showed further increases of Type I fibers, until finally, in the two older children studied (5 and 8 years), there was a predominance of Type I fibers. This persisted in adults between ages 56 to 70, but after age 70 Type I fibers diminished, so that the ratio of slow to rapid fibers in the 78 to 81 year-old group was 3:2. This study shows that in contrast to other skeletal muscles the fiber distribution in the external sphincter ani muscle is not established from the beginning, but is the result of a developmental process. The predominance of Type II (twitching) fibers explains the state of reflex continence of the young infant. With increasing maturation of tonic Type I fibers, an additional voluntary component to continence is made possible with the help of the supporting pelvic musculature. This maturation is determined by the increasing strain on the pelvic floor as the child learns to sit and walk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466873 TI - Ligation of the patent ductus arteriosus in premature infants--indications and procedures. AB - Premature newborns with patent ductus arteriosus can be managed by prostaglandin inhibition, but this medical treatment carries a high risk of renal failure, and other complications such as necrotizing enterocolitis and hematologic disorders have been described. Echocardiography gives an early confirmation of shunt and surgical treatment may be proposed. The aortic arch anatomy in the premature infant may not be as simple to determine as the anatomy of an older child. In the premature infant the use of a clip for patent ductus arterious closure seems the best technique, avoiding circular dissection of the ductus. We report our experience of 68 cases operated upon. PMID- 8466874 TI - The treatment of duplication thumbs in children. About a series of 32 patients. AB - 29 children with 32 duplicated thumbs were followed up. Wassel's classification was used: type I (3 cases), type II (8 cases), type IV (16 cases), type V (3 cases), type VII (2 cases). There were no type III or VI cases. Seven cases were not operated on (minor abnormalities, refusal by the parents). Simple surgical ablation was performed in 12 cases, ablation with reconstruction in 10 cases, ablation with pollicisation in one case, ablation with longitudinal osteotomy in one case. Finally, Bilhaut's technique was performed in one case. 16 cases had a good result, 9 cases were disappointing with one case of stiffness, one step deformity, one protrusion of the metacarpal head and particularly 6 cases with joint instability. This latter complication is the most frequently encountered in various series and the authors emphasize the surgical precautions to avoid its occurrence. PMID- 8466875 TI - Investigations on mechanism of Salter-1-fractures of the greater trochanter. AB - This study aims at clarifying why the apophysis of the greater trochanter very rarely separates, in contrast to other apophyses of the hip region. The inclination and area measurement of the greater trochanteric growth plate and the mode of insertion of the muscles on the apophysis were analyzed on the basis of 16 anatomic femoral specimens from newborn to children of 14 years of age. The physiological muscle cross section Q of the muscles inserting at the greater trochanter was determined on 6 specimens. In a cross-sectional radiological study, carried out on 1350 hip joints of healthy children, the inclination of the greater trochanter growth plate was measured. The anatomical and radiological findings show that the nearly plane-shaped greater trochanter growth plate remains inclined at a 50 degree angle to the horizontal body line and is loaded from a diagonally craniolateral direction throughout the total growth period. The lateral surface of the apophysis is covered by a fibrous connection which joins the insertion areas of the gluteus medius, minimus and vastus lateralis muscles. The vastus lateralis muscle is intimately bound to the vastus intermedius muscle by fibrous tissue. According to the results of the physiological muscle cross sections these four muscle groups can form a counteracting muscle sling, which transforms the traction forces at the surface of the greater trochanter into pressure forces in line with a tension band effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466876 TI - Jugular phlebectasia in children. AB - Jugular phlebectasia is a congenital dilatation of jugular vein which appears as a soft, compressible mass in the neck only during straining or crying. It should be differentiated from laryngocele, cysts and tumors of neck which may also appear during straining. Comparable ultrasonography (US) and computerized tomography (CT) are diagnostic methods to distinguish the pathology. Four children with jugular phlebectasia diagnosed by venography, US and CT are reported. Surgical excision of the dilated segment was performed in each case. The inevitability of surgical intervention is discussed. PMID- 8466877 TI - Lipid secreting breast carcinoma in childhood: a case report. AB - A ten-year-old girl was admitted to our hospital with a mass in the left breast after a local recurrence following a resection done in a district hospital three months earlier. A modified radical mastectomy with axillary lymph node dissection was performed in our department. Histological examination revealed a lipid secreting carcinoma (lipid-rich carcinoma) of the breast. To our knowledge she is the first case in childhood in the literature and is therefore reported. PMID- 8466878 TI - Traumatic rupture of the thoracic aorta in childhood with special reference to the therapeutic strategy. AB - Acute traumatic tear of the thoracic aorta is extremely rare in childhood. Based upon our own experience with two children, the essential diagnostic and therapeutic measures are discussed with special reference to timing of surgery. Aortic disruption must be suspected in a child who sustains severe blunt chest injury and develops an abnormally wide mediastinum. Definite diagnosis is established by aortography or computed tomography. The appropriate therapeutic approach is determined by the clinical symptomatology and particularly by the severity of concomitant lesions. In the absence of a significant hemothorax and if no difference in pulse amplitude between upper and lower extremities is evident, the risk of free aortic rupture with intrathoracic exsanguination is presumed to be rather low if the patient reaches the hospital alive. In that situation, the continuity of the injured aorta is maintained by the adventitia and surrounding mediastinal structures. Therefore, these patients may derive the best benefit from an initially conservative management including pharmacological intervention to reduce the risk of free aortic rupture. This concept is particularly indicated if aortic disruption is associated with severe concomitant injury such as intraabdominal or intracranial lesions. Such injuries preclude safe aortic repair immediately after establishment of diagnosis. Delay of aortic repair until recovery from associated major injury allows heparinization and the use of a pump oxygenator, which is regarded as the most effective method to prevent spinal cord ischemia and to reduce the risk of paraplegia. PMID- 8466879 TI - Gastrointestinal manifestations of neurofibromatosis in childhood. AB - Von Recklinghausen's neurofibromatosis (VRN) is a familial disorder characterised by a generalized neuroectodermal dysplasia--symptomatic involvement of the gastrointestinal tract is rare. We report on our experience with two children who had proven gastrointestinal neurofibromas and highlight the need for careful assessment in children with VRN who develop abdominal pain. PMID- 8466880 TI - Intestinal hemorrhage three years after incidental appendectomy by total inversion. AB - A late hemorrhagic complication of incidental appendectomy by entire inversion is reported in a liver transplant child. The use of proper surgical technique for inversion appendectomy is emphasized, including total devascularization of the appendix before inverting it. PMID- 8466881 TI - Lung growth and maturation in the rat model of experimentally induced congenital diaphragmatic hernia. AB - This paper explores whether, in addition to the previously described lung hypoplasia with arteriolar hypermuscularization present in the nitrofen-induced foetal rat model of congenital diaphragmatic hernia (CDH), there are changes in the respiratory exchange epithelium, consistent with the hypothesis that abnormal surfactant production and/or release could account in part for the respiratory insufficiency in this condition. Foetal lungs from nitrofen-treated rats were obtained on the 21st day of gestation, weighed and processed for light and electron-microscopic studies and compared to controls of the same age. Tissues from 29 control and 26 CDH foetuses were examined. In addition, lungs from 19 foetuses born to nitrofen-treated dams but without CDH were also studied. The lungs from CDH animals were hypoplastic by weight in comparison with control ones and so were those from treated foetuses without CDH. Airway branching was arrested in CDH at the pseudo-glandular stage of development, corresponding to the 16th day of gestation and the very narrow air spaces were lined by generally mature type II pneumocytes rich in glycogen and lamellar bodies corresponding to the 19th day of gestation. This pattern was in contrast to that of the control foetuses which had a normal terminal sac pattern with flat type I pneumocyte lining corresponding to their gestational age. Nitrofentreated animals without CDH had intermediate patterns. These findings support the hypothesis that the surfactant-producing system has the same lesions in this experimental model as in other less-affordable ones, like the foetal lamb one. Further studies on the contribution of this factor to the altered respiratory physiology in CDH using this model are warranted. PMID- 8466882 TI - Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men. AB - The present study was carried out to explore the possible relation of plasma plasminogen activator inhibitor-1 (PAI-1), fibrinogen, and factor VII levels to other risk factors for coronary heart disease (CHD) and to serum sex hormone levels. The study group comprised 48 apparently healthy men. To avoid the confounding factor of obesity, correlations were determined in the 30 men in this group with a body mass index (BMI) < 26.4, after controlling for age. PAI-1 correlated with testosterone, estradiol/testosterone, and free testosterone/testosterone (FT/T), and fibrinogen correlated with FT/T. All three hemostatic factors correlated with glucose and with the ratio of cholesterol/high density lipoprotein cholesterol, while PAI-1 correlated with diastolic blood pressure. To test the effect of obesity, correlations were determined in the entire group of 48 men, which included 18 subjects with a BMI > 26.4. All three hemostatic factors correlated with BMI in this group after controlling for age; however, on controlling for testosterone, only PAI-1 correlated with BMI. Fibrinogen correlated with age in both groups after controlling for testosterone or BMI. These correlations support the hypothesis that PAI-1, fibrinogen, and factor VII are related to other risk factors for CHD and that an alteration in the sex hormone milieu may be the underlying factor linking them. PMID- 8466883 TI - Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness. AB - Recent intravascular ultrasound experience challenges the accuracy of ultrasonic measurement of arterial wall thickness. We reevaluated the correlation between histological and sonographic measurements of intima-media thickness using standard transcutaneous vascular technology. Carotid and femoral arterial segments were imaged before and after fixation using a 7-MHz linear-array vascular transducer. Log compression and beam orientation were varied. Mean intima, media, and adventitia thicknesses were measured and compared with corresponding histological tunica. Tissue processing caused 2.5% shrinkage. Intraobserver reading error was 0.7% for histology and 5.4% for sonography. Ultrasound overestimated the thickness of the intima and adventitia and underestimated the thickness of the media. For combined intima-media thickness, the differences between histology and imaging were insignificant, averaging 4% for the carotid artery and 9% for the femoral artery in the far-wall projection. In the near-wall projection, sonographic intima-media thickness was 20% less than that determined histologically. We conclude that ultrasonography is limited mainly by axial resolution in quantifying the dimensions of individual arterial tunica but is capable of accurately measuring far-wall intima-media thickness. PMID- 8466884 TI - Visceral fat loss measured by magnetic resonance imaging in relation to changes in serum lipid levels of obese men and women. AB - The effect of weight reduction on serum lipids in relation to visceral fat accumulation was studied in 78 healthy obese subjects (40 premenopausal women and 38 men) aged 27-51 years and with an initial body mass index of 30.7 +/- 2.2 kg/m2 (mean +/- SD). The subjects received a 4.2 MJ/day energy-deficit diet for 13 weeks. Magnetic resonance imaging was used to assess abdominal fat areas before and after weight loss. Weight reductions of 12.6 +/- 3.2 kg in men and 11.7 +/- 3.8 kg in women resulted in larger reductions in the fasting serum levels of total cholesterol (p < 0.05), low density lipoprotein cholesterol (p = 0.06), and triglycerides (p < 0.01) and a larger increase in the high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio (p = 0.05) in men compared with women. Men also lost more visceral fat (p < 0.0001), whereas the reductions in the total and subcutaneous abdominal fat depots were similar. In women, visceral fat loss was significantly related with an increase of the high density lipoprotein cholesterol level, independent of the degree of total fat loss. In men, however, no significant correlations were observed between changes in visceral fat and any of the serum lipids. Comparisons of average changes in obese men and women suggest that visceral fat loss is associated with an improvement of the serum lipid profile. However, correlation analysis does not support a critical role of visceral fat in determining serum lipid concentrations on an individual level, except for an improvement of the high density lipoprotein cholesterol level with visceral fat loss in obese women. PMID- 8466885 TI - The low HDL cholesterol/high triglyceride trait. AB - In 748 probands and 3,283 first-degree relatives from the Collaborative Lipid Research Clinics (LRC) Family Study, our specific aim was to examine the degree to which low (bottom decile) high density lipoprotein cholesterol (HDL-C, hypoalpha) and high (top decile) triglyceride (TG, hyperTG) levels occur conjointly (CT) and the extent to which these characteristics were shared within families. To control for family size and permit a comparison with the proband percentages, mean familial percentages of HDL-C/TG abnormalities were calculated. Concurrent low HDL-C and high TG levels were present in 2.7% of the probands, a value that was enriched to 12.7% (p = 0.003) of their associated first-degree relatives. If the proband had a low HDL-C value, 7.7% (p = 0.013) of relatives had CT. Familial (proband and at least one first-degree family member share the same lipoprotein/lipid phenotype) hypoalpha was observed in 2.4% of families while familial hyperTG was observed in 4.1%. Familial CT was seen in approximately 0.7%. If the proband had CT, 80% of their families had at least one other first-degree member with an HDL-C/TG abnormality, whereas the corresponding percentage for families associated with probands with only hypoalpha was 64% and for those with hyperTG alone, 54%. A broadly shared environmental factor cannot easily explain the familial association of hypoalpha, hyperTG, and CT. In probands with low HDL-C values alone or the conjoint low-HDL-C/high-TG trait, family screening is extremely valuable because low HDL-C/high TG is enriched in the respective family members, a conjoined trait closely associated with increased coronary heart disease risk. PMID- 8466886 TI - Circulating lipid hydroperoxide levels in human hyperhomocysteinemia. Relevance to development of arteriosclerosis. AB - Elevated circulating homocyst(e)ine is a risk factor for occlusive vascular disease. We explored whether elevated plasma homocyst(e)ine is associated with increased plasma lipid hydroperoxides that might trigger vascular disease. We obtained plasma containing high levels of homocyst(e)ine from four patients with a homozygous deficiency of cystathionine beta-synthase activity and also from four heterozygotes with a deficiency of this enzyme after an oral methionine load. The mean plasma non-protein-bound homocyst(e)ine level in all subjects was more than 11-fold higher than the mean normal fasting value. Levels of high density lipoprotein (HDL) cholesteryl ester hydroperoxides (CEOOH), normalized against the concentration of free cholesterol in HDL, were not elevated in our subjects (mean +/- SD, 0.0091 +/- 0.0061) compared with values for 14 fasting healthy donors (0.0164 +/- 0.0086). An inverse dependency was observed between plasma total homocyst(e)ine and HDL CEOOH (r = -0.78, p = 0.023). Also, the ubiquinol-10/ubiquinone-10 ratio in HDL, which is expected to fall during oxidative stress, increased with plasma homocyst(e)ine. Since HDL contains the majority of detectable plasma lipid hydroperoxides, of which CEOOHs are the most abundant, our data suggest that an elevated plasma homocyst(e)ine level does not enhance oxidative stress, increase the levels of lipid hydroperoxides in plasma, or generate vascular damage by this mechanism. PMID- 8466887 TI - Endogenous sex hormones and ischemic heart disease in men. The Caerphilly prospective study. AB - Numerous case-control studies have suggested that elevated levels of endogenous estrogen and low levels of testosterone are associated with ischemic heart disease (IHD) in men. These findings were tested in the Caerphilly study of 2,512 men from the general population who were aged 45-59 years at baseline and were followed for 5 years. Some 153 men experienced a new episode of IHD (fatal and nonfatal) during the period of follow-up. Baseline values of estradiol were marginally higher in subjects who developed IHD than in those who did not, but the difference was not statistically significant. Plasma values of testosterone were similar in the two groups. Among quintiles of the distribution of the hormone values, the incidence of IHD was similar in the case of estradiol; there was also no clear trend in the case of testosterone. These findings provide no support for the suggestion that plasma estradiol or testosterone are primary risk factors for IHD, although the associations between plasma testosterone and other probable risk markers (triglycerides, insulin, body mass index, and high density lipoprotein cholesterol) indicate the possibility that testosterone may play an indirect role in the pathogenesis of IHD. PMID- 8466888 TI - Increased postprandial lipemia in Apo A-IMilano carriers. AB - Plasma lipid/lipoprotein changes were monitored after a fat load (65 g fat per square meter body surface area) in six carriers of the apolipoprotein A-IMilano (A-IM) variant and six age- and sex-matched control subjects. The magnitude of postprandial lipemia, calculated as the area under the curve (AUC) described by plasma triglyceride (TG) level versus time, was threefold higher in the A-IM carriers; however, after correction for the different baseline TG levels, it was similar to control subjects. Moreover, the magnitude of postprandial lipemia was positively correlated with baseline TG in both A-IM carriers (r = 0.77) and control subjects (r = 0.80), indicating that fasting TGs are a major determinant of postprandial response in all subjects. Postprandial lipemia was also inversely correlated with high density lipoprotein (HDL) and HDL2 cholesterol in both groups (A-IM, r = -0.81 and -0.79; control subjects, r = -0.87 and -0.94). Different from those in control subjects, the plasma apo A-I levels in the A-IM carriers decreased progressively while apo B increased up to 4 hours but decreased thereafter. Postprandial rises of low density lipoprotein TG but not of HDL-TG AUC were significantly higher in the A-IM carriers, even after normalization for the different fasting concentrations. These data show that the low plasma HDL levels of A-IM carriers, which are secondary to a primary structural alteration of the major HDL apolipoprotein, are associated with elevated fasting and postprandial TG levels and an anomalous postprandial redistribution of TG among lipoprotein classes. PMID- 8466889 TI - Binding of 111In-labeled LDL to platelets of normolipemic volunteers and patients with heterozygous familial hypercholesterolemia. AB - Low density lipoproteins (LDLs) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding of these radiolabels onto platelets of normolipemic volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites capable of binding 1,757 +/- 289 ng protein of 111In-LDL per 10(9) platelets (dissociation constant [Kd], 6 +/- 3 micrograms protein/mL) in healthy volunteers and significantly (p < 0.001) lower amounts in the FH patients (mean, 633 +/- 341 ng protein/10(9) platelets; Kd, 10 +/- 5 micrograms protein/mL). The capacity of native LDL to displace bound 111In-LDL by half amounted to 10 +/- 4 micrograms protein/mL in volunteers and 22 +/- 8 micrograms protein/mL in FH patients (p < 0.001). Treatment with gemfibrozil alone or in combination with cholestyramine in 10 patients resulted in increased 111In-LDL binding by platelets (470 +/- 307 [mean +/- SD] ng protein/10(9) platelets before therapy, 948 +/- 650 ng protein/10(9) platelets after 2 months of therapy [p < 0.01], and 1,272 +/- 701 ng protein/10(9) platelets after 6 months of therapy [p < 0.01]). Significant correlations between 111In-LDL binding capacity and apolipoprotein B (r = -0.83, p < 0.001) and LDL cholesterol (r = 0.80, p < 0.000) concentrations were found. Patients with clinically manifested atherosclerosis (p < 0.01) and those with diabetes mellitus (p < 0.05) had significantly lower platelet LDL binding sites. The findings demonstrate 111In lipoprotein-specific binding sites on human platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466890 TI - Occlusive arterial thrombosis in cynomolgus monkeys with varying plasma concentrations of lipoprotein(a). AB - Lipoprotein(a) (Lp[a]) is a newly recognized risk factor for the development of coronary heart disease and stroke in human beings; however, the mechanisms by which Lp(a) increases the risk of coronary heart disease remain unclear. The purpose of this study was to examine the effects of Lp(a) on the occurrence of occlusive arterial thrombosis. Occlusive arterial thrombus formation was examined in 18 cynomolgus monkeys with high plasma Lp(a) concentrations (> 35 mg/dL, n = 6), intermediate Lp(a) concentrations (20-25 mg/dL, n = 6), and low Lp(a) concentrations (< 12 mg/dL, n = 6). A Goldblatt clamp was positioned around the left common carotid artery to produce a stenotic segment, and the artery was pinch-injured with needle holders. A 20-MHz Doppler velocity crystal, placed distal to the stenosis/injury site, was used to detect cyclic flow reductions (indicative of transient thrombosis) or permanent cessation of flow velocity (indicative of more stable occlusive thrombosis). All monkeys with high Lp(a) concentrations developed permanent cessation of flow, whereas only one of six arteries from low-Lp(a) monkeys developed permanent cessation of flow (p < 0.05). Arteries from monkeys with intermediate Lp(a) concentrations developed pronounced cyclic reductions of flow but did not progress to permanent cessation of flow. There were no differences in plasma von Willebrand factor activity among the three groups. Immunohistochemical analysis of the damaged arterial segments indicated incorporation of Lp(a) into the adventitia, media, and intima of arteries from monkeys with low and high plasma Lp(a) concentrations, as well as the presence of an occlusive thrombus in arteries that developed permanent cessation of flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466891 TI - Lower-extremity arterial disease in older hypertensive adults. AB - Lower-extremity arterial disease (LEAD) is common in older adults, particularly those with systolic hypertension. In a subgroup of 1,775 participants of the Systolic Hypertension in the Elderly Program, LEAD was assessed noninvasively by the ratio of the ankle to arm blood pressure, the ankle-arm index (AAI). LEAD was defined as an AAI of < or = 0.9 in either leg. The prevalence of LEAD was 25% in white men, 38% in black men, 23% in white women, and 41% in black women. About half of those with LEAD had mild disease (AAI, 0.8-0.9), and only 1-3% had a positive Rose questionnaire for intermittent claudication. The prevalence increased with age (p < 0.01) and was consistently higher in blacks than whites (p < 0.01), although there were no significant differences between men and women. Even in the absence of risk factors such as smoking and diabetes, blacks had a higher prevalence of LEAD than whites. Associations of LEAD with cardiovascular risk factors (high density lipoprotein cholesterol, systolic blood pressure, and smoking) appeared to be similar in blacks and whites, although relations were not always statistically significant in subgroups stratified by race and sex. Independent factors associated with the presence of LEAD included age, black race, smoking, diabetes mellitus, history of myocardial infarction or angina, systolic blood pressure, lower high density lipoprotein cholesterol, and body mass index. LEAD is common in older men and women with systolic hypertension, particularly blacks. However, very few have symptoms of claudication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466892 TI - HMG CoA reductase inhibitors. In vivo effects on carotid intimal thickening in normocholesterolemic rabbits. AB - The in vivo activity of different 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (vastatins) on neointimal formation induced by insertion of a flexible collar around one carotid artery of normocholesterolemic rabbits was investigated. The contralateral carotid artery served as a sham control. Pravastatin, lovastatin, simvastatin, and fluvastatin were given mixed with food at daily doses of 20 mg/kg body wt for 2 weeks starting on the day of collar placement. The treatment with vastatins did not modify rabbit plasma cholesterol concentrations. The neointimal formation was assessed by measuring the cross sectional thickness of intimal and medial tissues of fixed arteries with light microscopy. Fourteen days after collar placement, intimal hyperplasia (mostly cellular) was pronounced in treated carotid arteries. The intimal/medial (I/M) tissue ratio was 12-fold higher in treated arteries than in arteries without the collar (0.36 +/- 0.04 versus 0.03 +/- 0.02). Animals treated with lovastatin (n = 12), simvastatin (n = 12), and fluvastatin (n = 12) showed significantly less neointimal formation; I/M tissue ratios were 0.24 +/- 0.03, 0.20 +/- 0.03, and 0.17 +/- 0.03, respectively. The inhibition elicited by pravastatin (n = 12, 0.32 +/- 0.03) did not reach statistical significance. alpha-Actin antibody immunofluorescence analysis of serial sections revealed that cells present in the hyperplastic intima were mostly myocytes. Rates of intimal myocyte proliferation were also measured by incorporation of 5-bromo-2'-deoxyuridine, a thymidine analogue, into replicating DNA. Immunofluorescence analysis showed that 5-bromo 2'-deoxyuridine was actively incorporated into intimal myocytes after ++reinsertion of the collar, with a labeling index (percent of labeled myocytes) of 2.15 after 14 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466893 TI - Two patterns of LDL metabolism in normotriglyceridemic patients with hypoalphalipoproteinemia. AB - The objective of this study was to determine whether normotriglyceridemic patients with low levels of high density lipoprotein (HDL) cholesterol have concomitant defects in the metabolism of low density lipoproteins (LDLs). To address this question, measurements of turnover rates of apolipoprotein A-I (apo A-I) and LDL apolipoprotein B (apo B) were made in 36 middle-aged men with low HDL cholesterol (< 40 mg/dL), normal triglyceride (< 250 mg/dL), and normal total cholesterol (< or = 90th percentile) levels. Similar measurements were made in eight hypertriglyceridemic men having low HDL levels. For control, turnover rates of LDL apo B were measured in 24 healthy, normolipidemic men, and apo A-I kinetics were determined in 20 other healthy men with normal HDL cholesterol levels. In all patients with low HDL levels, fractional catabolic rates (FCRs) for apo A-I were increased compared with control subjects; in contrast, input rates for apo A-I in low-HDL patients were similar to control. Hypertriglyceridemic patients had significantly higher FCRs for LDL (0.463 +/- 0.040 pool/day, [mean +/- SEM]) than control subjects (0.328 +/- 0.008 pool/day, p < 0.001). In normolipidemic patients having low HDL, a bimodal pattern of LDL apo B kinetics was observed. For 23 low-HDL patients, FCRs for LDL apo B averaged 0.450 +/- 0.017 pool/day and were significantly higher than control values. Additionally, in these patients, levels of very low density lipoprotein plus intermediate density lipoprotein (VLDL+IDL) cholesterol and VLDL+IDL apo B were higher than in control subjects (54 +/- 3 versus 32 +/- 3 mg/dL and 25 +/- 2 versus 18 +/- 1 mg/dL, respectively). The remaining 13 low-HDL patients had lower and essentially normal FCRs for LDL (0.300 +/- 0.009 pool/day); these patients also had relatively low levels of cholesterol and apo B in VLDL+IDL. Thus, two patterns of LDL kinetics were present in normotriglyceridemic patients with low HDL levels. One pattern was indistinguishable from that typically present in patients with hypertriglyceridemia, whereas the other was similar to normal control subjects. These two patterns of LDL-apo B kinetics may reflect different mechanisms for the causation of low HDL cholesterol concentrations. PMID- 8466894 TI - Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. AB - Experimental and epidemiological evidence supports the hypothesis that oxidation of low density lipoprotein (LDL) appears to be important in mediating the atherogenicity of LDL. To test this hypothesis in humans, it will be necessary to perform intervention studies in large populations. We performed two studies to assess the effectiveness of supplementation with beta-carotene and vitamin E, used alone and in combination with each other, and with vitamin C, to protect LDL from oxidation. In phase 1, after a placebo period, eight subjects were given beta-carotene (60 mg/day) for 3 months, then beta-carotene plus vitamin E (1,600 mg/day) for another 3 months, and then beta-carotene plus vitamin E plus vitamin C (2 g/day) for 3 months. During phase 2, beta-carotene and vitamin C were discontinued, and subjects took only vitamin E for 5 months. During each period, LDL samples were isolated, and measurements of susceptibility to oxidation were performed. beta-Carotene levels in LDL increased nearly 20-fold, but LDL susceptibility to oxidation did not change. Addition of vitamin E increased LDL vitamin E levels nearly 2.5-fold, and this decreased LDL oxidation 30-40%. During the vitamin C supplementation period, plasma levels of beta-carotene and vitamin E rose, but only beta-carotene increased in LDL. However, the susceptibility of LDL to oxidation in this period was not decreased further. During phase 2, when subjects took only vitamin E, LDL susceptibility to oxidation was decreased by 50% as measured by thiobarbituric acid-reactive substances, conjugated dienes, and lipid peroxide formation as well as by macrophage degradation. Thus, long term supplementation with large doses of vitamin E alone, but not beta-carotene, conferred increased protection to LDL in in vitro assays of oxidation. These data should be useful in planning therapeutic strategies to test the antioxidant hypothesis in humans. PMID- 8466895 TI - Comparison of supplementation of RRR-alpha-tocopherol and racemic alpha tocopherol in humans. Effects on lipid levels and lipoprotein susceptibility to oxidation. AB - It has been suggested that alpha-tocopherol, a safe and effective antioxidant, be used in clinical trials to evaluate the ability of antioxidant therapy to inhibit atherosclerosis. Recent reports, however, have raised the possibility that there may be greater enrichment of plasma low density lipoprotein (LDL) in alpha tocopherol resulting from the use of the naturally occurring RRR-alpha-tocopherol isomer compared with the other isomers present in the synthetic racemic form of alpha-tocopherol. Therefore, we fed equal dosages (1,600 mg/day) of the two forms of vitamin E to 16 men and women for 8 weeks and compared the effects of this supplementation on the susceptibility of isolated lipoproteins to oxidation. Neither form of vitamin E had appreciable effects on lipid or lipoprotein levels. alpha-Tocopherol levels in LDL increased at a similar rate in both groups and were nearly twofold higher than baseline levels by the end of the study. The susceptibility of LDL to oxidation was measured by formation of conjugated dienes, lipid peroxides, and thiobarbituric acid-reactive substances, as well as by macrophage degradation of LDL exposed to oxidizing conditions in vitro. The susceptibility of LDL to oxidation was decreased in both vitamin E groups compared with the baseline value, and this reduction occurred to a similar extent in both vitamin E-supplemented groups. alpha-Tocopherol levels in LDL also strongly correlated with all measures of LDL oxidation. This study demonstrates that, at this dosage, supplementation with either the natural or synthetic form of alpha-tocopherol provided equal antioxidant protection to LDL. PMID- 8466896 TI - Effect of intramolecular cross-links on the enthalpy and quaternary structure of the intermediates of oxygenation of human hemoglobin. AB - We have reported [Bucci, E., Fronticelli, C., & Grycznski, Z. (1991) Biochemistry 30, 3195-3199] that in human and bovine hemoglobins the release of heat at the subsequent steps of oxygenation is not constant. This is especially evident in the binding of the third O2 molecule, which is an endothermic event. This phenomenon was attributed to peculiar conformations of the intermediates of oxygenation, not included in the fundamental R/T transition of the system. To test this hypothesis, we have explored the effect of conformational constraints on the thermodynamics of the intermediates of oxygenation. The assumption was that intramolecular constraints would stabilize the intermediates into conformations similar to the R and T forms reducing the variability of their enthalpies. We have analyzed the temperature dependence of the oxygen binding isotherms of human hemoglobin cross-linked either between the beta 82 or between the alpha 99 lysines by bis(3,5-dibromosalicyl)fumarate. The measurements were perfomred at pH 9.0 in 0.1 M borate buffer in order to avoid thermal effects due to oxygen-linked binding of anions and protons. The data were analyzed singularly by local procedures and simultaneously using global procedures. The two cross links had opposite effects. The cross-link between the beta-subunits decreased while that between the alpha-subunits increased the endothermic behavior of the third step of oxygenation. Also, the cross-link between the beta-subunits increased the fractional amount of the triligated species at intermediate stages of oxygenation, while that between the alpha-subunits decreased this quantity to hardly detectable values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466897 TI - Association of the A subunits of recombinant placental factor XIII with the native carrier B subunits from human plasma. AB - Interactions of a recombinant human placental protein (rA2) expressed in yeast and considered to be identical to the catalytic A2 subunits of factor XIII, the fibrin stabilizing factor zymogen, were examined with the native carrier subunits (B2) of the factor isolated from human plasma. Nondenaturing electrophoresis and HPLC gel-filtration experiments showed a tight binding of rA2 to B2 for forming an ensemble similar to that of plasma factor XIII (A2B2). In the presence of excess B2, however, some higher ordered oligomers (rA2Bn, where n > 2) were also seen in electrophoresis. The same technique revealed a microheterogeneity in the rA2 preparation; nevertheless, all isoforms could bind to B2. By employing an ELISA procedure for measuring free B2 in mixtures with rA2, an apparent binding constant of 4 x 10(7) M-1 was derived for the association of rA2 with B2. Fluorescence depolarization was used to monitor the heterologous association of rA2 with fluorescein-labeled B2F as well as the dissociation of the rA2B2F structure. The former was characterized by an increase, and the latter by a decrease, in the fluorescence anisotropy of the system. Binding of rA2 to B2F (pH 7.5, mu = 0.315, 37 degrees C) was not influenced by low concentrations of Ca2+ (< or = 30 mM), and rA2B2F proved to be quite stable under these conditions. Much higher concentrations of Ca2+, as well as higher ionic strengths, were required to dissociate this assembly. By contrast, release of B2F from the thrombin modified rA2'B2F occurred rapidly in the presence of low concentrations of Ca2+ at low ionic strength.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466898 TI - Kinetics of bisulfite-induced cytosine deamination in single-stranded DNA. AB - The rate of bisulfite-induced deamination of cytosine to uracil in single stranded (ss) DNA at physiological temperature and pH was monitored by a sensitive genetic assay. The assay is based on reversion of a mutation in the lacZ alpha gene of bacteriophage M13mp2 and employs ung- (NR9404) and ung+ (MC1061) bacterial strains which are isogenic except for uracil glycosylase activity. For ss DNA incubated with 1-50 mM bisulfite and transfected into an ung cell strain, the reversion frequency increased linearly with time of incubation and with concentration of bisulfite. Of 54 revertants sequenced, all were C-->T transitions. Reduction in reversion frequency upon transfecting ss DNA into ung+ cells indicated that the majority of mutations were occurring via a uracil intermediate. Assuming that all revertants arose via uracil, the pseudo-first order rate constant for deamination in 10 mM sodium bisulfite and 10 mM Hepes NaOH, pH 7.4, at 37 degrees C as measured by transfecting into an ung- cell strain was 3.5 x 10(-10) s-1, as compared to a spontaneous background rate constant of 0.6 x 10(-10) s-1 in buffer alone. PMID- 8466899 TI - Inhibitor binding to the Phe53Trp mutant of HIV-1 protease promotes conformational changes detectable by spectrofluorometry. AB - HIV-1 protease contains two identical, conformationally mobile loops, known as flaps, which form in part the binding pockets for substrates and inhibitors. We have constructed a site-specific mutant of the protease in which residues Phe-53 and Phe-153 at the end of the flaps have been mutated to Trp residues, in order to incorporate a specific fluorescent probe to monitor conformational changes upon the binding of an inhibitor. The Phe53Trp (F53W) mutant of HIV-1 protease was expressed in Escherichia coli and purified from bacterial lysates. Analysis of the purified mutant protease demonstrated that its kinetic properties were highly similar to those of the wild-type protease. While binding of a potent peptide-analogue inhibitor (Ki = 9 nM) to the wild-type enzyme led to no change in protein fluorescence, a 5-8% increase in fluorescence was observed with the F53W mutant, indicating an enhancement of the Trp fluorescence due to flap movement upon inhibitor binding. Investigation of the kinetics of the F53W protease-inhibitor binding by stopped-flow spectrofluorometry revealed a rapid increase in protein fluorescence upon formation of the enzyme-inhibitor complex. These data were consistent with a one-step mechanistic model of inhibitor binding in which flap movement was concomitant with inhibitor binding, from which respective rate constants of association and dissociation of 2.5 x 10(6) M-1 s-1 and 0.023 s-1 were obtained. PMID- 8466900 TI - Transcription termination factor rho: the site of bicyclomycin inhibition in Escherichia coli. AB - Bicyclomycin is a novel, commercially important antibiotic. Information concerning the site of bicyclomycin inhibition in Escherichia coli has been obtained by the production of bicyclomycin resistant mutants by UV irradiation. Selection by growth in the presence of bicyclomycin of a plasmid clone library generated from a highly resistant mutant in recipient antibiotic-sensitive host cells (E. coli strain W3350) has led to the characterization of three different plasmids that confer drug resistance, which contained the gene encoding the transcription termination factor, rho. These mutant rho genes contained single base changes at nucleotide positions 656, 796, and 1009. Preliminary mechanistic information has been obtained by monitoring the polyC-dependent ATPase activity of rho in the absence and presence of bicyclomycin and dihydrobicyclomycin. Addition of bicyclomycin to aqueous solutions containing rho and ATP led to a decrease in the release of inorganic phosphate with an I50 value of 60-70 microM bicyclomycin. This inhibition is comparable to the drug concentration needed to inhibit bacterial growth on plates. No loss of activity was observed when a similar concentration of dihydrobicyclomycin was used in place of bicyclomycin, while use of 10-fold higher concentrations of this derivative led to partial rho inhibition. PolyC-dependent ATPase activity from partially purified rho isolated from the mutant BCMr108 was not inhibited by bicyclomycin at concentrations (200 microM) found to completely inhibit wild-type rho. These cumulative findings are consistent with the notion that bicyclomycin expresses its activity by interfering with the polyC-dependent ATPase activity of rho. PMID- 8466901 TI - Effect of thymine tract length on the structure and stability of model telomeric sequences. AB - DNA from the telomeres at the ends of eukaryotic chromosomes contains a stretch of simple tandemly repeated sequences in which clusters of G residues alternate with clusters of T/A sequences along one DNA strand. Model telomeric G-clusters form four-stranded structures in Na+ or K+, stabilized by Hoogsteen pairing between G bases. DNA containing a single copy of the G-cluster can self-associate to form tetramers, with a parallel-stranded, right-handed helical structure. Two copies of the 3'-terminal G strand form a folded-back hairpin that dimerizes to create an antiparallel quadruplex structure. We show here that the tetrameric structure is strongly influenced by the T residue flanking either side of the G cluster. The parallel tetraplex formed by single copies of the sequences dTnG4 is most stable for n = 1 and least stable for n = 8, the longest tract we have studied. At least two thymine residues are required to allow formation of antiparallel folded-back hairpin dimers from two-copy oligomers of sequence d(TnG4)2 in Na+; additional T's destabilize this structure. In K+, the predominant structure formed is the four-stranded parallel tetramer in all cases. Kinetic analysis indicates that the quadruplex structure formed by Oxytricha telomeric DNA overhangs in the presence of Na+ arises by dimerization of two Hoogsteen base-paired hairpins, with a relatively low energy barrier. PMID- 8466902 TI - Important 2'-hydroxyl groups within the core of a group I intron. AB - The catalytic activity of a group I intron is dependent on a core structure, much of which is not exposed to solvent. In order to study the structure of the core, an efficient bimolecular reaction has been developed: the 5'-component is a molecule of about 300 bases which contains the 5'-splice-site and terminates in the loop established by P8, and the 3'-component is a 24 base long oligoribonucleotide which includes the 3'-regions of the P8 and P7 helices with their joining region, J8/7. J8/7 is thought to play several roles including binding the helix containing the 5'-splice-site. P7 forms a major portion of the guanosine binding site required for splicing. We have modified the bimolecular system to make it amenable to kinetic analysis and have used it to study the role of the ribose sugars in the oligomer. Multiple deoxyribonucleotide substitution in the J8/7 region completely blocked 5'-splice-site cleavage even though the Kd was only reduced about 5-fold. This supports the idea that the ribose phosphate backbone in J8/7 plays a key role in catalysis. Individual substitutions at G303 and A306 reduced the rate of catalysis 5-10-fold. The G303 substitution blocked GTP-independent hydrolysis of the 5'-splice-site. The region spanning the junction of P8 and J8/7 was also highly sensitive to multiple deoxyribonucleotide substitution; however, only in the case of C298 did an individual substitution have any effect on cleavage. Deoxyribonucleotide substitution in the 3'-section of P7 was less severe, although kcat/Km in low GTP was down 70-fold. PMID- 8466903 TI - Sources of hydrogen abstraction by activated neocarzinostatin chromophore. AB - Activation of the enediyne neocarzinostatin chromophore (NCS-Chrom) by thiol addition at C-12 generates a diradical species with radical centers at C-2 and C 6, which abstract hydrogens from deoxyribose in the minor groove of DNA. Since hydrogen abstraction from DNA accounts for only part of the hydrogen incorporated at these sites, it is important to determine the other possible sources. At low concentration of thiol, a condition resembling that during NCS-Chrom-induced DNA damage, the major non-DNA hydrogen donation source was found to be the carbon bound hydrogen of the aqueous methanol solvent, rather than the expected sulfur bound hydrogen of the thiol. Further, experiments with the gamma-L-glutamyl-DL cysteinylglycine labeled with deuterium on the alpha- or beta-carbons to the sulfur showed small amounts of internal transfer of hydrogen into C-2 of the drug from the naturally occurring L,L diastereomer only. Quantitation of the hydrogen transfer was accomplished by separation of the L,DL diastereomeric mixtures of the thiol-NCS-Chrom adducts. In all, these various hydrogen donation sources can account for at least 70-80% of the hydrogen incorporated at C-2 of the drug under DNA damage conditions. Selective quenching of the radical at C-2 could account for the predominance of single-stranded over double-stranded DNA lesions. PMID- 8466904 TI - Exclusive production of bistranded DNA damage by calicheamicin. AB - Bistranded DNA damage produced by the enediyne antitumor antibiotic calicheamicin (CAL) was examined in plasmid DNA and in a model site for CAL-mediated DNA damage containing the sequence AGGA.TCCT. CAL was observed to produce bistranded DNA damage to the virtual exclusion of single-strand (SS) lesions. Without expression of drug-induced abasic sites as strand breaks, CAL activated by 10 mM glutathione produced equal numbers of DS and SS breaks in plasmid DNA. However, cleavage of drug-induced abasic sites with hydrazine and putrescine resulted in a dramatic increase in the appearance of bistranded damage, with ratios of DS to SS breaks of approximately 6:1 and approximately 24:1, respectively. A similar bias for DS lesions was noted in CAL-mediated damage in the AGGA.TCCT model sequence, in which evidence for a 4'-hydroxylated abasic site was observed on the AGGA strand. These model DNA systems revealed three important features of the bistranded damage produced by CAL. First, the major lesion produced by CAL is a bistranded lesion consisting of an abasic site on one strand and a direct strand break on the other. Second, 3'-phosphoglycolate residues resulting from CAL-induced C4' hydrogen abstraction at the C of AGGATC were restricted to bistranded lesions. This unusual behavior of the C4'-chemistry of both CAL and the related neocarzinostatin (NCS) is consistent with an intermediate in the partitioning that is dependent on bistranded lesions. Finally, 4-hydroxythiophenol activated CAL to produce a ratio of DS to SS lesions of approximately 10:1, as opposed to the approximately 1:30 ratio noted previously for NCS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466905 TI - Identification of a compact DNA-binding domain in the gene 5 protein of Pf1 bacteriophage. AB - The structure of the gene 5 protein of filamentous bacteriophage Pf1 and its interaction with viral DNA have been investigated by a series of limited proteolysis experiments. The ability of purified proteolytic fragments of the Pf1 gene 5 protein to bind oligonucleotides and polynucleotides was monitored by gel retardation and fluorescence. The results show the presence of a compact DNA binding "core" domain consisting of residues 1-112 of the protein, which is protected from proteolysis in the nucleoprotein complex. Digestion of the free gene 5 protein with subtilisin produces a smaller fragment (residues 7-102) which can no longer bind DNA. Although the N-terminal "core" domain shows full DNA binding activity by fluorescence, the gel retardation experiments suggest reduced kinetic stability of this domain in complexes with oligonucleotides, resulting from the removal of residues 113-144 from the C-terminus of the protein. The sequence of the C-terminal 32 amino acid residues is unusual, with a high proportion of alanine, glutamine, and proline residues which may be related to the role of this sequence in stabilizing the complex. PMID- 8466906 TI - Differential scanning calorimetry of the irreversible denaturation of Escherichia coli glucosamine-6-phosphate deaminase. AB - The thermal denaturation of Escherichia coli glucosamine-6-phosphate deaminase (G6PD) at neutral pH was studied by means of differential scanning calorimetry (DSC). In the concentration range 0.6-7.3 mg mL-1, the denaturation of this hexameric enzyme was completely irreversible as judged by the absence of any endotherm on rescanning of previously scanned samples. However, the study of the effect of scanning rate on DSC curves indicated that the denaturation of G6PD is, most likely, a complex process which includes transitions in equilibrium as well as an irreversible step; in addition, it was found that application of the equilibrium formalism to the analysis of calorimetric data seems to be justified in this case, provided that scanning rates used are above 0.75 K min-1. The calorimetric and van't Hoff enthalpies for G6PD were 1260 +/- 118 and 160 +/- 27 kcal mol-1, respectively, indicating the presence of intermediates in the process. Accordingly, the DSC curves were adequately fitted to a model including six two-state sequential transitions. The observed protein-concentration dependence of the temperature at the maximum heat capacity, Tm, for each of the individual transitions suggests that G6PD dissociates to dimers in two consecutive steps. Using a model that includes dissociation explicitly, we calculated the thermodynamic parameters for each step. From this data, the enthalpy and free energy for the disruption of one dimer-dimer contact were roughly estimated, at pH 7.1 and 51 degrees C, as 57 and 2.1 kcal mol-1, respectively. PMID- 8466907 TI - Conformational dynamics of cytochrome P-450cam as monitored by photoacoustic calorimetry. AB - Conformational transitions of cytochrome P-450cam following the dissociation of CO from the ferrous heme were investigated by using photoacoustic calorimetry. The effect of substrate association on the acoustic signal was also examined. Results show that the conformational dynamics of cytochrome P-450cam substrate free protein occur faster than 10 ns, which is the time scale of the instrument response. The enthalpy and volume change for the dissociation reaction are 2.2 kcal mol-1 and 1.8 mL mol-1, respectively. Upon addition of camphor, the reaction is markedly slowed. An intermediate is formed whose lifetime is 130 ns at 17 degrees C. The overall enthalpy and volume changes are -15.9 kcal mol-1 and 10.3 mL mol-1, respectively. These results, together with published transient Raman spectra [Wells, A. V., Pusheng, L., Champion, P. M., Martinis, S. A., & Sligar, S. G. (1992) Biochemistry 31, 4384-4393] suggest that camphor leaves the heme pocket concomitant with the photoinduced expulsion of CO into the solvent and induces a considerable conformational change in the protein. PMID- 8466908 TI - Pathway of disulfide-coupled unfolding and refolding of bovine alpha-lactalbumin. AB - alpha-Lactalbumin's four disulfide bonds have been used to probe the nature of its native, molten globule, and unfolded states. The Ca2+ concentration could be used to vary the stability of the native state because it binds a single calcium ion with high affinity. In the Ca(2+)-bound native state, the Cys6-120 and Cys28 111 disulfides were reduced sequentially, reflecting their relative accessibilities. The native disulfides do not stabilize the native conformation as much as in other proteins, nor was the unfolding process as cooperative. After two disulfides were reduced, only part of the protein molecule appeared to remain folded. In the absence of Ca2+, the native state was much less stable, and a molten globule-type conformation tended to be adopted. Formation of disulfide bonds in the reduced protein was initially noncooperative and nonspecific. The molten globule state increased the rate at which disulfides were formed, by tending to keep close in space cysteine residues that are distant in the sequence. A large number of nonnative disulfide pairings were preferred, and the disulfides were not stabilized to any great extent. The alpha-lactalbumin molten globule seems to be stabilized by nonspecific interactions and without a well defined topology. The native protein was regenerated only when Ca2+ bound to and stabilized the three-disulfide intermediate lacking the Cys6-120 disulfide, which then rapidly formed the fourth disulfide bond. The rate-limiting intramolecular steps were rearrangement of disulfide bonds to native combinations in species with two and three disulfide bonds. PMID- 8466909 TI - Structural characterization of the disulfide folding intermediates of bovine alpha-lactalbumin. AB - Specific three- and two-disulfide intermediates that accumulate transiently during reduction of the disulfide bonds of Ca(2+)-bound bovine alpha-lactalbumin have been trapped, isolated, and characterized. The three-disulfide intermediate was shown to lack the Cys6-120 disulfide bond, confirming the observations of others. The newly-recognized two-disulfide form has been shown to lack the Cys6 120 and Cys28-111 native disulfide bonds. The remaining native disulfide bonds in the two partially reduced derivatives of alpha-lactalbumin are stable only when the proteins are in a Ca(2+)-bound state. Otherwise, they adopt an equilibrium between molten globule and unfolded conformations, and rapid thiol-disulfide interchange occurs, at a rate as high as when the proteins are fully unfolded in 8 M urea, to generate distinct mixtures of rearranged products. Urea gradient electrophoresis, circular dichroism, fluorescence, and ANS binding have been combined to give a detailed structural picture of alpha-lactalbumin, its derivatives with native and with nonnative disulfide bonds, and the fully reduced protein. The native structure of alpha-lactalbumin appears to be split by selective disulfide bond cleavage into at least one subdomain, which retains the Ca(2+)-binding site. The alpha-lactalbumin molten globule state is shown largely to result from nonspecific hydrophobic collapse, to be devoid of cooperative or specific tertiary interactions, and not to be stabilized substantially by the native or rearranged disulfide bonds. PMID- 8466910 TI - Time-resolved and equilibrium measurements of the effects of poly(ethylene glycol) on small unilamellar phospholipid vesicles. AB - The effects of poly(ethylene glycol) (PEG) on sonicated unilamellar vesicles made of phosphatidylcholine have been examined. Stopped-flow and equilibrium data are presented for vesicle aggregation, vesicle leakage, lipid mixing, and aqueous contents mixing. Vesicle aggregation is detected as a monoexponential increase in light scattering, for PEG concentrations between 5 and 10%. In the region between 10-15% and 23-27% PEG, under our experimental conditions, the increase in light scattering follows a more complex biexponential kinetics, and, under these conditions, vesicle aggregation is accompanied by lipid mixing, a combination of events denoted as "close apposition". Above 23-27% PEG, the increase in light scattering is accompanied by fast lipid mixing, and also mixing of aqueous contents, all this being indicative of vesicle fusion; in addition, leakage occurs under these circumstances. Fusion takes place at high PEG concentrations, as indicated above, without any dilution step. From a methodological point of view, the Tb/DPA assay is shown to be more appropriate than the ANTS/DPX method for leakage and fusion studies in the presence of PEG. PMID- 8466911 TI - Contribution of hydrogen bonding to lipid-lipid interactions in membranes and the role of lipid order: effects of cholesterol, increased phospholipid unsaturation, and ethanol. AB - It is proposed that increased phospholipid unsaturation in membranes and perturbation by agents such as ethanol weaken interlipid hydrogen bonding involving water and that the process is independent of effects on lipid order. To investigate this, the rates of phospholipid desorption, as a measure of the strength of interlipid interactions, from "donor" lipid vesicles was determined. This was accomplished using (7-nitrobenzo-2-oxa-1,3-diazole-4-yl)aminohexanoate (C6-NBD) labeled phospholipids, the rate of desorption being followed from changes in fluorescence with time. The rates of desorption of the NBD phospholipids from phosphatidylcholine (PC) donor vesicles was in the order phosphatidylcholine (PC) > phosphatidylserine (PS) > phosphatidylethanolamine (PE), the slower rates in the PS and PE reflecting direct interlipid hydrogen bonding. For PC, the interlipid hydrogen bonding was restricted to the "hydration layer", the network of hydrogen-bonded water molecules extending between phospholipid head groups. The rate of C6-NBD-PC desorption was elevated with higher levels of donor PC sn-2 unsaturation, due the increased head group spacing weakening the lipid-lipid interactions that occur via the hydration layer. Ethanol also increased the rate of NBD-phospholipid desorption from donor PC vesicles in the order PC > PS > PE, showing that PC interactions, here limited to the weaker hydrogen-bonded water molecule network, were more susceptible compared to stronger, direct interlipid hydrogen bonds involving PE and PS. The relative magnitude of the ethanol-induced increase in the desorption rate was amplified with higher levels of donor lipid sn-2 unsaturation. Cholesterol had little effect on the rate of phospholipid desorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466912 TI - Physical properties of recombinant apolipoprotein(a) and its association with LDL to form an LP(a)-like complex. AB - Recombinant apolipoprotein(a) has been studied by hydrodynamic techniques and electron microscopy. Recombinant apo(a) was primarily a monomer in solution with an s0(20,w) of 9.3 S, a D20,w of 2.29 ficks, and a molecular weight of 325,000 from sedimentation equilibrium and 318,000 from combining the sedimentation and diffusion coefficients. A small amount, approximately 10%, of the recombinant apo(a) was present as a high molecular weight aggregate. The Stokes radius of the monomer, determined either from the diffusion coefficient or by combining the sedimentation equilibrium data with the sedimentation velocity data, was 94 A. The frictional ratio was 2.2, suggesting a highly asymmetric or random coil structure. In the electron microscope, recombinant apolipoprotein(a) was visualized as a long, highly flexible chain of domains forming large, open coiled structures on the EM grid with contour lengths of about 800 A. Addition of 6 aminohexanoic acid at 50 mM, a concentration which should saturate the weak lysine binding sites, did not alter the sedimentation behavior. In vivo, apolipoprotein(a) is associated tightly with LDL to form a highly atherogenic lipoprotein, Lp(a). A single molecule of recombinant apo(a) also associated tightly with LDL to yield a 13.3-S Lp(a)-like complex. This complex dissociated upon the addition of 50 mM 6-aminohexanoic acid. A novel sucrose gradient centrifugation technique was employed to determine a dissociation constant for the reversible equilibrium between recombinant apo(a) and LDL; at physiological ionic strength the dissociation constant was 0.3 nM. Raising the salt concentration to 5 M NaBr caused the dissociation constant to increase to 500 nM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466913 TI - Differential effects of the reversible thiol-reactive agents arsenite and methyl methanethiosulfonate on steroid binding by the glucocorticoid receptor. AB - The hormone binding domain of the glucocorticoid receptor contains a unique vicinally spaced dithiol, and when it is bound by arsenite under conditions that are specific for reaction with vicinally spaced dithiols versus monothiols, steroid binding activity is eliminated [Simons, S. S., Jr., Chakraborti, P. K., & Cavanaugh, A. H. (1990) J. Biol. Chem. 265, 1938-1945]. The vicinally spaced dithiol lies in a region of the receptor that appears to be a contact site for hsp90, which is required for the high-affinity steroid binding conformation of the glucocorticoid receptor [Dalman, F. C., Scherrer, L. C., Taylor, L. P., Akil, H., & Pratt, W. B. (1991) J. Biol. Chem. 266, 3482-3490]. As part of a long-term project to develop a vicinal dithiol-specific agent that will permit studies of ligand-induced conformational changes in this region of the receptor, we have examined here the differential effects of two reversible thiol-reactive agents, arsenite and MMTS. At low concentration, arsenite inactivates the steroid binding activity of the unliganded receptor in a vicinal dithiol-specific manner, whereas dissociation of steroid from untransformed, transformed, or DNA-bound transformed receptors occurs only at concentrations typical of monothiol interactions. MMTS produces a unique bimodal effect on the steroid binding capacity of the unliganded receptor at pH 9 that is pH-dependent and becomes essentially unimodal at physiological pH. Whereas arsenite disrupts the dexamethasone-receptor complex more readily than the triamcinolone acetonide-receptor complex, MMTS has the opposite effect. During treatment for 1 h at 0 degree C, neither reagent causes dissociation of hsp90 from the receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466914 TI - Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei. AB - The surface of the bloodstream forms of Trypanosoma brucei is covered by the abundant glycosylphosphatidylinositol-anchored variant surface protein (mfVSG). During differentiation of bloodstream forms to the insect-stage or procyclic forms, the mfVSG is replaced by another glycoprotein, designated procyclic acidic repetitive protein (PARP) or procyclin. Shortly after differentiation is triggered in vitro, a cell-associated fragment of mfVSG can be detected which is subsequently released into the culture medium. In the case of the mfVSG of the variant clone MITat 1.4 (470 amino acid residues), fragmentation occurs close to the COOH-terminus (Gln433 or Thr434) as shown by NH2-terminal sequencing, metabolic labeling experiments, and molecular weight determinations by laser desorption/ionization mass spectrometry. Two invariant surface glycoproteins, which are anchored in the membrane by hydrophobic sequences close to their COOH termini, are lost from the surface with similar kinetics as mfVSG. The data suggest that trypanosomes synthesize or activate a developmentally-regulated proteinase which degrades the glycoproteins at the surface, at the membrane lining the flagellar pocket, and/or in an early endocytic compartment. PMID- 8466915 TI - Biosynthesis of lipoic acid: characterization of the lipoic acid auxotrophs Escherichia coli W1485-lip2 and JRG33-lip9. AB - The abilities of the Escherichia coli lipoic acid auxotrophs W1485-lip2 and JRG33 lip9 to grow on succinate medium in the presence of octanoate, 8 mercaptooctanoate, or 6-mercaptooctanoate have been determined. Both organisms are mutated in lipA. Neither organism can use octanoate or 6-mercaptooctanoate for production of lipoate, but the lip2 allele can use 8-mercaptooctanoate. Chromosomal DNA from the auxotrophs was amplified by PCR using primers derived from the DNA sequence of wild-type lipA and then sequenced. Both mutants contain single G/C to A/T mutations in lipA, resulting in conversion of Ser307 into Phe in W1485-lip2 and Glu195 into Lys in JRG33-lip9. These results support the hypothesis that lipA is involved in the sulfur insertion step(s) of lipoate biosynthesis and indicate that it is possible to selectively block formation of the C8-S bond through suitable mutation in lipA. PMID- 8466916 TI - A reexamination of the folding mechanism of dihydrofolate reductase from Escherichia coli: verification and refinement of a four-channel model. AB - The mechanism of folding of dihydrofolate reductase from Escherichia coli was reinvestigated by studying the unfolding and refolding kinetics using absorbance and fluorescence spectroscopies. The original kinetic model proposed that folding involved a series of native, intermediate, and unfolded forms which interconverted through four independent channels linked by slow cis/trans isomerization reactions at Xaa-Pro peptide bonds [Touchette, N. A., Perry, K. M., & Matthews, C. R. (1986) Biochemistry 25, 5445]. Recently, alternative sequential models have been proposed [Frieden, C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4413; Kuwajima et al. (1991) Biochemistry 30, 7693] which challenge the original proposal. Stopped-flow studies of the intrinsic tryptophan fluorescence demonstrated the presence of three (and tentatively four) kinetic phases in unfolding which correlated well with four phases previously observed in refolding experiments. By monitoring the binding of the inhibitor methotrexate during folding at varying relative concentrations of inhibitor to protein, it was found that the selective loss of the slow-folding phases at substoichiometric levels could only be explained by a four-channel folding model. Double-jump experiments (native-->unfolded-->native) showed that the four refolding channels are populated within 20 s at 15 degrees C and are not likely to be due to proline isomerization. Reverse double-jump experiments (unfolded-->native-->unfolded) demonstrated that interconversions between native conformers are more rapid than originally proposed. Interestingly, the majority of the protein folds through a channel to a native conformer that is minimally populated at equilibrium. This implies that although the folding of dihydrofolate reductase is ultimately under thermodynamic control, kinetic factors contribute to the transient populations of native species during folding. PMID- 8466917 TI - Three-state analysis of sperm whale apomyoglobin folding. AB - We give a quantitative description of the urea- and acid-induced transitions of apomyoglobin at 0 degree C and 2 mM sodium citrate. Our data consist of two series of unfolding curves: (1) acid-induced unfolding carried out in the presence of various concentrations of urea and (2) urea-induced unfolding at various pH values. A three-state equation is derived which relates the stability of three different conformations of apomyoglobin (native [N], unfolded [U], and intermediate [I]) as a function of urea and of pH. This equation fits our data reasonably well. The parameters which give the best fit have both thermodynamic and structural implications for N, I, and U. Specifically, I is closer in Gibbs energy to U than to N, indicating that side-chain packing results in much of the stability of native protein structure. The equilibria between N and I and between I and U are equally sensitive to urea, suggesting that much of the surface of I is inaccessible to solvent. The acid-induced transition in which N unfolds can be described as the result of titration of approximately two histidines with low pKaS in N. Under physiological conditions (neutral pH, no urea) I is the most stable non-native conformation. PMID- 8466918 TI - Study of a fatty acid binding site of interphotoreceptor retinoid-binding protein using fluorescent fatty acids. AB - Interphotoreceptor retinoid-binding protein (IRBP) is a 140-kDa glycolipoprotein which constitutes about 70% of the soluble protein of the retinal interphotoreceptor matrix. Much is known concerning its role in the transport of retinoids between photoreceptor cells and pigment epithelium but little is known about its interactions with lipids. Here we have examined the physicochemical characteristics of a fatty acid binding site of IRBP using a set of fluorescent fatty acid analogs with an anthracene moiety attached at different positions along the hydrocarbon chain. The results show that fatty acids are bound in a hydrophobic environment as indicated by a blue shift in fluorescence maxima and by a increase in quantum yield of the bound ligand. There is a single specific fatty acid binding site for each molecule of IRBP with an apparent Kd = 3.6 x 10( 7) M. There is a nonradiative energy transfer from tryptophan residues to bound ligand. The interactions of IRBP and bound fatty acid are sensitive to denaturation by increasing concentrations of urea as judged by changes in nonradiative energy transfer efficiency and the quantum yield of bound probe. Quantum yields of bound fatty acid analogs varied with position of the fluorophore along the hydrocarbon chain and had the lowest values for the fluorophore located at the midpoint. Probing of the microenvironment of bound fluorophore with a quencher indicated a highly structured binding site. PMID- 8466920 TI - Solution conformation of a deoxynucleotide containing tandem G.A mismatched base pairs and 3'-overhanging ends in d(GTGAACTT)2. PMID- 8466919 TI - Fluorophore environments in membrane-bound probes: a red edge excitation shift study. AB - A shift in the wavelength of maximum fluorescence emission toward higher wavelengths, caused by a shift in the excitation wavelength toward the red edge of the absorption band, is termed the Red Edge Excitation Shift (REES). This effect is mostly observed with polar fluorophores in motionally restricted media such as very viscous solutions or condensed phases. In this paper, we report the red edge excitation shift of a membrane-bound phospholipid molecule whose headgroup is covalently labeled with a 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) moiety. When incorporated into model membranes of dioleoyl-sn-glycero-3 phosphocholine (DOPC), the NBD-labeled phospholipid (NBD-PE), exhibits a red edge excitation shift of 10 nm. In addition, fluorescence polarization of NBD-PE in membranes shows both excitation and emission wavelength dependence. The nonpolar membrane probe 1,6-diphenyl-1,3,5-hexatriene (DPH) does not show red edge excitation shift in model membranes. The lifetime of NBD-PE in DOPC vesicles was found to be dependent on both excitation and emission wavelengths. These wavelength-dependent lifetimes are correlated to the reorientation of solvent dipoles around the excited-state dipole of the NBD moiety in the membrane. The magnitude of the red shift in the emission maximum for NBD-PE was found to be independent of temperature, between 12 and 54 degrees C, and of the physical state (gel or fluid) of the membrane. Taken together, these observations are indicative of the motional restriction experienced by this fluorophore in the membrane. Red edge excitation shift promises to be a powerful tool in probing membrane organization and dynamics. PMID- 8466921 TI - Release of protein 4.1-rich vesicles from diamide-treated erythrocytes under hydrostatic pressure. AB - The effect of cross-linking of membrane proteins on vesiculation under high pressure (2.0 kbar) of human erythrocytes was examined. To get the large molecular weight aggregates characterized by cross-linking of cytoskeletal proteins with integral ones, the erythrocytes were pretreated with diamide under pressure (1.0 kbar) where no vesiculation occurs. Vesicles released at 2.0 kbar from such erythrocytes contained protein 4.1 as major membrane protein. Upon reduction of cross-linking by dithiothreitol prior to vesiculation, the released vesicles contained membrane proteins similar to intact cells. On the other hand, in the erythrocyte pretreated with diamide at atmospheric pressure, no such large molecular weight aggregate was observed and the membrane protein composition of the vesicles released from the cells at 2.0 kbar was also similar to that of intact cells. These results suggest that the membrane protein composition of released vesicles is much affected by the properties of cross-linking of membrane proteins in erythrocytes. PMID- 8466922 TI - Monitoring of unbound protein in vesicle suspensions with off-null ellipsometry. AB - In studies on the binding of proteins to small unilamellar phospholipid vesicles (SUV), the concentration of unbound protein usually remains unknown, because the vesicles cannot be separated from the bulk solution. In the present study, this limitation was overcome by addition of a supported planar phospholipid bilayer to the cuvette containing a vesicle suspension. Ellipsometric measurement of the protein adsorption velocities on this bilayer allowed determination of the concentrations of unbound protein. At high protein concentrations the adsorption is rapidly completed and the usual null-ellipsometry is too slow to obtain well defined initial adsorption rates. Therefore, an off-null technique was developed, allowing measurement of the adsorbed protein mass at time intervals of 20 ms. Binding of prothrombin and coagulation factor Xa was measured in SUV suspensions prepared from a 20% dioleoylphosphatidylserine (DOPS) and 80% dioleoylphosphatidylcholine (DOPC) phospholipid mixture. For prothrombin, a dissociation constant Kd = 140 +/- 27 nM (mean +/- S.E.) and maximal surface concentration gamma max = (8.9 +/- 0.8) x 10(-3) mole of protein per mole of lipid, were obtained. For factor Xa, these values were Kd = 49.6 +/- 6.3 nM and gamma max = (23.0 +/- 1.4) x 10(-3) mole of protein per mole of lipid. These binding parameters are similar to those obtained earlier for planar bilayers. Apparently, the binding of factor Xa and prothrombin is not dependent on surface curvature. PMID- 8466923 TI - Purification and functional reconstitution of the 2-oxoglutarate/malate translocator from spinach chloroplasts. AB - The chloroplast 2-oxoglutarate/malate translocator was solubilized from envelope membranes by the detergent n-dodecyl beta-D-maltoside and purified to apparent homogeneity by anion-exchange chromatography followed by gel permeation chromatography. During the purification procedure, the activity of the translocator was monitored by functional reconstitution into phospholipid vesicles. The purified translocator protein has an apparent molecular mass of about 45,000 as revealed by SDS-PAGE. Based on the specific reconstituted transport activity, the purification was about 31-fold with an overall yield of identical to 50%. The substrate specificity of the purified translocator closely resembles that described for the native transport system in intact chloroplasts. PMID- 8466924 TI - Bactericidal catechins damage the lipid bilayer. AB - The mode of antibacterial action of, the green tea (Camellia sinensis) extracts, (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin (EC) was investigated. Strong bactericidal EGCg caused leakage of 5,6-carboxyfluorescein from phosphatidylcholine liposomes (PC), but EC with very weak bactericidal activity caused little damage to the membrane. Phosphatidylserine and dicetyl phosphate partially protected the membrane from EGCg-mediated damage when reconstituted into the liposome membrane with PC. EGCg, but not EC, caused strong aggregation and NPN-fluorescence quenching of PC-liposomes and these actions were markedly lowered in the presence of negatively charged lipids. These results show that bactericidal catechins primarily act on and damage bacterial membranes. The observation that Gram-negative bacteria are more resistant to bactericidal catechins than Gram-positive bacteria can be explained to some extent by the presence of negatively charged lipopolysaccharide. PMID- 8466925 TI - Effect of fenvalerate, a pyrethroid insecticide on membrane fluidity. AB - Fenvalerate is a commonly used pyrethroid insecticide, used to control a wide range of pests. We have studied its interaction with the membrane using fluorescence polarization and differential scanning calorimetry (DSC) techniques. Fenvalerate was found to decrease the DPH fluorescence polarization value of synaptosomal and microsomal membrane, implicating that it makes the membrane more fluid. At different concentrations of fenvalerate, the activation energy of the probe molecule in the membrane also changes revealed from the change in slope of the Arrhenius plot. At higher concentrations the insecticide slowly saturates the membrane. The effects of fenvalerate on model membrane were also studied with liposomes reconstituted with dipalmitoylphosphatidylcholine (DPPC). Fenvalerate decreased the phase transition temperature (Tm) of DPPC by 1.5 C degrees at 40 microM concentration, but there was no effect on the cooperativity of the transition as interpreted from the DSC thermogram. From the change in the thermogram profile with fenvalerate it has been interpreted that it localizes in the acyl chain region of the lipid, possibly between C10 and C16 region and weakens the acyl chain packing. Fenvalerate was also found to interact with DPPC liposomes containing cholesterol to fluidize it. PMID- 8466926 TI - The effect of general anesthetics on the dynamics of phosphatidylcholine acetylcholine receptor interactions in reconstituted vesicles. AB - The interaction of general anesthetics at the lipid/protein interface of the nicotinic acetylcholine receptor reconstituted in dioleoylphosphatidylcholine bilayers at various lipid/protein ratios has been studied using the electron spin resonance spectra of phosphatidylcholine spin-labeled at the fourteenth acyl carbon (14-PCSL). In addition to the bilayer spectrum, the spin label reported a more motionally restricted environment whose contribution increased with increasing protein/lipid ratio. Exchange between these two environments occurred at a rate of approx. 6 x 10(7) s-1. The motionally restricted, protein-associated 14-PCSL had a rotational correlation time of about 10-20 ns, an order of magnitude slower than when in the bilayer. Addition of 1-hexanol (up to 16 mM) to the reconstituted receptor perturbed the acyl chains of the bulk lipid phase, but the motional properties of the lipid acyl chains at the protein/lipid interface near the membrane center were not significantly perturbed on the EPR motional time-scale. Similarly, anesthetics that were less effective at perturbing the bilayer, such as pentobarbital (up to 2 mM) and isoflurane (7 mM), did not perturb the lipid/protein interface on the conventional EPR motional time scale. PMID- 8466927 TI - A microscopic model for lipid/protein bilayers with critical mixing. AB - A statistical mechanical lattice model is proposed to describe the phase diagram of phospholipid bilayers with small transmembrane proteins or polypeptides. The model is based on the extended Pink-Green-Chapman model (Zhang et al. (1992) Phys. Rev. A 45, 7560-7567) for pure lipid bilayers which undergo a first-order gel-fluid phase transition. The interaction between the lipid bilayer and the protein or polypeptide is modelled using the concept of hydrophobic matching. The phase diagram has been derived by computer-simulation techniques which fully account for thermal density fluctuations and which operate on the level of the free-energy thereby permitting an accurate identification of the phase boundaries. The calculations predict a closed loop of gel-fluid coexistence with a lower critical mixing point. Specific-heat traces across the phase diagram are also presented. The theoretical results for the phase diagram, the specific-heat function, and the transition enthalpy are related to recent experimental measurements on phospholipid bilayers mixed with synthetic transmembrane amphiphilic polypeptides or with gramicidin A. PMID- 8466928 TI - Use of irreversible electrical breakdown of lipid bilayers for the study of interaction of membranes with surface active molecules. AB - Lipid bilayers were formed in the presence of different macromolecules and high electrical fields were used to induce mechanical rupture of the membranes. The kinetics of pore formation during irreversible breakdown was studied as a function of the macromolecules. We observed that macromolecules having a strong binding affinity to the membrane alter the time course of pore formation significantly. We propose this method as a simple test for adsorption of macromolecules to membranes. PMID- 8466929 TI - Effect of the biochemical state of the Ca-ATPase protein of scallop sarcoplasmic reticulum on its interaction with trans-parinaric acid. AB - The polyene fluorescent probe trans-parinaric acid (tPA) was used to compare lipid-protein interactions in the scallop fragmented sarcoplasmic reticulum (FSR) between biochemical states where the Ca-ATPase molecules were arranged differently in the membrane and had different tertiary conformations. The state of the bulk lipid phase was examined over the temperature range -3 to +32 degrees C by exciting the tPA directly at 320 nm. The state of the system close to the Ca ATPase protein was followed over the same temperature range by indirectly exciting the tPA through resonance energy transfer from the Ca-ATPase protein, with approximately one twenty-fifth the quantum yield of the directly excited probe. Raising the tPA/lipid ratio in the membrane to high levels (approx. 1:9), caused the quantum yield of indirectly excited tPA to reach a maximum, which may reflect saturation of the annular lipid phase with the probe, or contribution to the fluorescence from indirectly excited tPA bound directly to the protein. In the presence of 0.1 M KCl, a thermal perturbation was observed at approx. 7 degrees C using indirect excitation when the Ca(2+)-binding sites on the Ca ATPase were occupied, and the subunits were disorganized. This transition was not detected in the presence of 0.1 M KCl and EGTA, when the Ca(2+)-binding sites were empty, and the Ca-ATPase subunits were organized in dimeric arrays. The transition seen with the E1(Ca2+)2 form of the membrane may involve an event at the protein/lipid interface, or a change in the environment of tPA bound to the Ca-ATPase. The temperature at which the perturbation occurs is close to that of a discontinuity in the Arrhenius plot of the Ca-ATPase enzyme activity determined in the presence of 0.1 M KCl (Kalabokis, V.N. and Hardwicke, P.M.D. (1988) J. Biol. Chem. 263, 15184-15188). No perturbation was observed in the bulk properties of the lipid component of the membrane in either the E1(Ca2+)2 or E2 states. PMID- 8466930 TI - Antimicrobial specificity and hemolytic activity of cyclized basic amphiphilic beta-structural model peptides and their interactions with phospholipid bilayers. AB - We synthesized a series of cyclic antiparallel beta-sheet model peptides with various ring sizes, which were designed on the basis of a cyclic beta-structural antibiotic, gramicidin S (GS); cyclo(Val-Orn-Leu-D-Phe-Pro)2, and investigated in terms of their antimicrobial activity and specificity against Gram-positive and Gram-negative bacteria and lytic activity for human erythrocytes. In our planning, in order to compare the peptides with GS, D-Phe-Pro sequence forming beta-turn in GS molecule remained unaltered and repeating sequences of alternately hydrophobic (Leu)-hydrophilic (Orn) residue were introduced into the beta-structural parts. CD study in acidic liposomes as well as leakage study of carboxyfluorescein encapsulated in phospholipid vesicles indicated that the peptides strongly interacted with lipid bilayers by taking an amphiphilic beta structure. Antimicrobial study showed that although GS is active only against Gram-positive bacteria, the antimicrobial spectra of the model peptides transformed gradually to be active against Gram-negative ones and finally only against Gram-negative bacteria whose repeating sequences increased. It should be noted that the designed cyclic model peptides show antibacterial activity but accompany no hemolysis. This indicates that an appropriate hydrophobicity together with a proper orientation of hydrophilic (cationic) and hydrophobic groups in cyclic beta-structural molecules can hold antimicrobial activity against both types of bacteria without damaging eukaryotic cells. PMID- 8466931 TI - Self-assembling properties of synthetic peptidic lipids. AB - Novel peptidic lipids were synthesized by the coupling of a linear oligopeptide as the hydrophilic moiety with a glutamic acid dialkylamide as the hydrophobic moiety. Their self-assembling properties were investigated. The critical aggregate concentrations (CAC) for the peptidic lipids with a double dodecyl group were in the range of 1.0 x 10(-5)-3.8 x 10(-5) M. The phase transition parameters and the aggregation morphologies in aqueous dispersion were largely dependent on the number and nature of the constitutive amino acid residues. Dark field optical microscopy demonstrated that the present peptidic lipids can form four types of stable morphologies in water, i.e., tubular structures, twisted ribbons, vesicles, and amorphous crystals. PMID- 8466932 TI - Magnetically induced orientation of phosphatidylcholine membranes. AB - Lipid bilayers prepared from natural phospholipids orient in magnetic fields with the long axis of the lipid molecules perpendicular to the magnetic field. This magnetically induced orientation was studied at high (11.7 Tesla (T)), mid (9.36 T), and low (4.68 T) magnetic field strengths using lipid aggregates prepared from natural and synthetic phosphatidylcholine analogs. Phosphatidylcholine analogs containing saturated diacylated chains (12 to 16 carbons/chain) exhibited extensive orientation of the lipid when bilayer formation occurred by gentle hydration conditions. Gentle hydration involved incubating dried phosphatidylcholine C above the main phase transition (Tm); brief shaking or swirling by hand was occasionally needed to completely disperse the lipids. The method of bilayer formation significantly influenced the amount of lipid that orients in magnetic fields. Thus the supramolecular structures (and % orientation) above Tm in an 11.7 T field of dimyristoylphosphatidylcholine (DMPC) bilayers are SUV (0%), LUV (approximately 15%), SPLV (approximately 40%), vortexed-MLV (approximately 60%) and non-vortexed MLV (approximately 90%). Single layered vesicles prepared by the REV method exhibited orientation at 11.7 T similar to LUV prepared by freeze thaw cycles. Aqueous dispersions of eggPC prepared by gentle hydration exhibit approximately 40% orientation at 11.7 T which decreased to approximately 30% orientation if 30% cholesterol is added to the membrane. Magnetic orientation of bilayers thus appears to be a general phenomenon for both saturated and unsaturated natural phospholipids either with or without cholesterol in the membrane. PMID- 8466933 TI - Localization of Cys-344 on the (Ca(2+)-Mg(2+)-ATPase of sarcoplasmic reticulum using resonance energy transfer. AB - 4-Bromomethyl-6,7-dimethoxy-coumarin labels the (Ca(2+)-Mg(2+)-ATPase of skeletal muscle sarcoplasmic reticulum at Cys-344. Resonance energy transfer has been used to measure the distance between this site and Lys-515 labelled with fluorescein isothiocyanate as about 37 A. The height of Cys-344 above the phospholipid/water interface has been measured by resonance energy transfer for the ATPase reconstituted into bilayers containing fluorescein-labelled phosphatidylethanolamine; the height was found to be about 45 A. None of these distances was found to alter on changing pH, or on addition of Mg2+, Ca2+ or vanadate. Quenching of the fluorescence of the coumarin-labelled ATPase with KI suggested that the fluorophore is not fully exposed on the ATPase. PMID- 8466934 TI - Plasma dependent pH sensitivity of liposomes containing sulfatide. AB - In this study we investigated the possibility to define relatively plasma-stable liposomal preparations in which the sensitivity to moderate drops of pH (i.e., from 7.4 to 6.8) would be induced by the presence of plasma itself. The liposome stability was monitored by determining the release of entrapped 5,6 carboxyfluorescein (CF). Using small unilamellar vesicles composed of egg phosphatidylcholine (EPC) and bovine brain sulfatide (CS) (4:1, molar ratio), the amount of CF released at pH 6.8 in the presence of 50% plasma was 3-fold that at pH 7.4, whereas no significant differences in the amount of CF released were observed when the same liposomes were incubated in buffer at pH 7.4 and 6.8, respectively. The increase in plasma induced leakage as a consequence of a drop in the pH medium, seems to specifically depend on the presence of sulfatide molecule in the bilayer since neither the acidic cholesterol 3-sulfate nor galactocerebroside, are able to induce pH sensitivity in EPC liposomes. Of all the plasma components considered (VLDL, LDL, HDL, protein fraction), VLDL seemed preferentially involved in the pH sensitivity induced by CS since they promoted an almost complete release of CF from EPC/CS small unilamellar vesicles. Thus, these liposomes are potentially a useful tool for a specific drug delivery to those pathological tissues such as tumors, inflammation sites and ischemic areas in which it is known that a lowering of the pH can occur. PMID- 8466935 TI - Tension-stabilized pores in giant vesicles: determination of pore size and pore line tension. AB - We present the first observations of giant, long-existing, stabilized pores in vesicle membranes. Using a new experimental technique for studying the electro permeabilization of lipid membranes, giant liposomes (from 25 to 56 microns in diameter) were subjected to single, square, electric pulses (duration 150 microseconds and electric field strength from 63 to 126 kV/m). The liposomes were held by a micropipet and small membrane tensions were created by controlling the pipet suction pressure. The liposomes were loaded with media having different refractive index from the outside solution, and, under these conditions, the formation of pores in the pressurized liposome could be visualized by the jet of inside solution that flowed out from the membrane pore. By adjusting the membrane tension, pores were kept open, and pore lifetimes could be varied from tenths of a second to several seconds. The pore size was determined from the volumetric flow in the pore region and the measured pressure differences across the bilayer. It was clear from the experiments that only one pore remained opened after the pulse. The estimated pore radii were on the order of one micrometer. The pores were in a quasi-stationary state and when they closed they did so spontaneously in a quick process (in milliseconds). The isotropic membrane tension was determined for the same measurements and from determinations of both pore size and dynamic membrane tension the pore line tension was found. The line tension of the pore region was determined for two lipid compositions, stearoyl oleoylphosphatidylcholine and stearoyl-oleoylphosphatidylcholine with 50 mol% cholesterol, and the obtained values for single bilayers were (0.92 +/- 0.07) x 10(-11) N and (3.05 +/- 0.12) x 10(-11) N, respectively. PMID- 8466936 TI - Evidence that liver microsomes of human neonates desaturate essential fatty acids. AB - delta 6- and delta 5-Desaturation of essential fatty acids of n-6 and n-3 series are required for the biosynthesis of polyunsaturated fatty acids (PUFAs), which are precursors of eicosanoids and constituents of membrane phospholipids. This pathway could be of special importance during the perinatal period, when PUFAs accretion in the central nervous system is very active. However, experimental evidence of delta 6- and delta 5-desaturase activities in man is very scarce, and no data are available for newborns. We report the delta 6- and delta 5-desaturase activities detected in human liver microsomes from three neonates who died from associated malformations. Radiochemical assays of delta 6- and delta 5-desaturase activities performed with reverse phase HPLC analysis of the products in the n-6 series ranged from 4.8-13.6 to 3.2-16.4 pmol substrate converted.min-1.mg-1 microsomal proteins, respectively. In the n-3 series delta 6-desaturase activity ranged from 5.3 to 12.8 pmol.min-1.mg-1. The relationships between enzyme activities and substrate concentrations suggest excess substrate inhibition for n 6 and not for n-3 fatty acids. These results demonstrate significant delta 6- and delta 5-desaturase activities in human liver of neonates, but this activity was lower than previously reported in adult humans and in mammals, especially rodents. PMID- 8466937 TI - Phase behavior of mixtures of DPPC and POPG. AB - The phase relation of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2 oleoyl-phosphatidylglycerol (POPG) has been determined by measurement of the endothermic transitions of mixtures of DPPC and POPG in 100 mM NaCl, 50 mM PIPES (pH 7.0). With the use of differential scanning calorimetry, the gel-liquid crystalline phase transitions of pure POPG and DPPC were estimated to be 274 K and 315.8 K, respectively. With mixtures, there was considerable broadening of the endotherms, but there was no evidence of immiscibility. At high and low mole fractions of DPPC, the observed transition regions are not different from that calculated assuming ideal behavior. However in the central region of the phase diagram, there were deviations from both the ideal liquidus and solidus curves. The chemical shift anisotropy of the 13C-labelled carbonyl carbon of pure DPPC was determined as a function of temperature. At 298 K, a broad peak characteristic of axially symmetric motional averaging of the shielding tensor was observed. At a temperature of 300 K, a narrow peak at 173 ppm was superimposed upon the broad peak. The magnitude of the narrow resonance increased with temperature over the range of 300 to 315 K with the spectrum obtained at the latter point almost completely devoid of any broad features. Spectra obtained with a 9:1 mole ratio of DPPC/POPG was very similar to that obtained with pure DPPC. However, with increasing amounts of POPG, both the temperature at which the narrow resonance appeared and the temperature at which only a narrow resonance was observed were reduced. Over the range of 0 to 50 mol % POPG, there was no major change in the width or shape of the spectra which contained only a broad or narrow resonance. Also for mol % of POPG of 20% and less, there was agreement between the temperature at which only the narrow component was observed and the completion of the main phase transition based on the DSC scans. However, at the two higher mol % of 33 and 50%, the temperature at which only the narrow component was observed was lower than the temperature established for the completion of the main phase transition. PMID- 8466938 TI - Lipids and oxidised lipids in human atheroma and normal aorta. AB - Lipids and oxidised lipids were analysed by GC and GC-MS in samples of human atheroma (necrotic gruel from the interior of advanced atherosclerotic plaques in the aorta) and human normal aorta (lesion-free intima plus inner media) from necropsy subjects. Cholest-5-en-3 beta,26-diol and cholest-5-en-3 beta,7 beta diol were detected in all the atheroma samples examined but not in significant amounts in normal aorta. In atheroma, cholest-5-en-3 beta,26-diol was approximately proportional to cholesterol. Several isomeric hydroxy octadecadienoic acids were detected in atheroma, and, in smaller amounts, in normal aorta. Many of the components of atheroma showed a high degree of cross correlation on linear regression analysis, whilst cross-correlations were somewhat weaker for normal aorta. Atheroma showed a vast accumulation of lipid, especially cholesterol, in comparison to normal aorta. The atheroma samples contained a larger proportion of linoleate relative to oleate than the normal aorta. Levels of fatty acids relative to cholesterol were lower for atheroma than for normal aorta. The chemical composition of atheroma appeared unrelated to the age of the subject, whereas age-related increases in linoleate, oleate and cholesterol content were seen in the samples of normal aorta. PMID- 8466939 TI - Effects of differentiation on the phospholipid and phospholipid fatty acid composition of N1E-115 neuroblastoma cells. AB - The effects of differentiation on the phospholipid and phospholipid fatty acid composition of N1E-115 neuroblastoma cells were determined. The cellular lipids were extracted on days 0, 3 and 7, following the addition of 1.2% dimethylsulfoxide to induce cellular differentiation. Proportions of ethanolamine glycerophospholipids (EtnGpl), phosphatidylinositol (PtdIns) and sphingomyelin (CerPCho) were significantly elevated following differentiation. The mole percentage of choline glycerophospholipids (ChoGpl) decreased with differentiation. The plasmalogens, both choline and ethanolamine, increased by 1.3- and 2.3-fold, respectively, during differentiation. The fatty acid composition of the phospholipid classes was also altered. PtdIns and ChoGpl had decreased proportions of polyenoic fatty acids, while these proportions were increased in EtnGpl. Both ChoGpl and EtnGpl had increased n-3/n-6 series fatty acid ratios, but this ratio was decreased in PtdIns. The mole percentage of arachidonic acid was significantly decreased in both PtdIns and ChoGpl, but elevated in EtnGpl and may be a result of the increase in ethanolamine plasmalogen. Thus, differentiation did not increase the overall mole percentage of polyenoic FA in the cells nor increase the n-6 series fatty acid proportions. We speculate plasmalogens may have a role in the differentiation process or in maintaining the cell in the differentiated state. PMID- 8466940 TI - Occurrence of two nonmethylene-interrupted delta 5 polyunsaturated fatty acids in a delta 6-desaturase-defective mutant of the fungus Mortierella alpina 1S-4. AB - Two non-methylene-interrupted fatty acids, 5(Z),11(Z),14(Z)-eicosatrienoic acid (20:3 delta 5) and 5(Z),11(Z),14(Z),17(Z)-eicosatetraenoic acid (20: 4 delta 5), were found in a delta 6-desaturase-defective mutant of Mortierella alpina 1S-4. 20: 4 delta 5 was detected only when growth was at a temperature lower than 24 degrees C or in a culture medium supplemented with either alpha-linolenic acid or 11(Z),14(Z),17(Z)-eicosatrienoic acid. 20: 3 delta 5 was found when growth was at 12-28 degrees C. The amount of 20: 3 delta 5 was greatest (27 mg g-1 dry mycelia) when growth was at 20 degrees C, and it accounted for about 7 wt% of the total fatty acids of the mycelia. The optimum temperature for the accumulation of 20:4 delta 5 was 12 degrees C; there was 6.4 mg 20: 4 delta 5/g dry mycelia. Most of these two fatty acids (more than 75 mol%) was in the triacylglycerol fraction. PMID- 8466941 TI - Fatty acid composition of lecithin is a key factor in bile metastability in supersaturated model bile systems. AB - We studied the effect of fatty acid saturation of biliary lecithin on bile metastability, determined by nucleation time, using model bile solutions with identical lipid compositions except for the lecithin species (total lipid concentration, 9 g/dl; cholesterol, 12 mM; lecithin, 31 mM, bile salts, 116 mM). Gel permeation chromatographic studies revealed that nonmicellar cholesterol distribution was inversely related to the degree of unsaturation of the lecithin species. Differential interference contrast microscopy and cholesterol crystal growth assay showed that a lower degree of saturation of the lecithin species was associated with a faster nucleation time and crystal growth rate. These results suggest that vesicular lecithin containing more unsaturated fatty acyl chains binds less tightly to cholesterol as compared with lecithin containing predominantly saturated fatty acids and that the biliary lecithin species modulates cholesterol crystal nucleation in bile. Also, the high ratio of cholesterol to lecithin (more than 1.0) was found in the crystal forming model biles, although the vesicle aggregation was not always observed prior to the cholesterol crystal formation. These findings indicated that there are different processes in cholesterol crystal nucleation, with or without vesicle aggregation, and that such processes depend, in part, on lecithin species in vesicles. PMID- 8466942 TI - Formation of prostanoids and hydroxy fatty acids by stimulated peritoneal mast cells: role of the dietary fat type in rat. AB - To study the influence of membrane fatty acid composition on the formation of prostanoids and hydroxy fatty acids by rat peritoneal mast cells (MC), animals were fed three different types of fatty acids: mackerel oil (MO), abundant in n-3 fatty acids; sunflower seed oil (SO), rich in linoleic acid; and hydrogenated coconut oil (HCO), mainly containing saturated fatty acids. The presence of n-3 fatty acids in the diet resulted in the incorporation of 20:5(n-3), 22:5(n-3) and 22:6(n-3) in MC phospholipids. A decrease of arachidonic acid, 20:4(n-6), was observed in MC-phospholipids of the MO-fed animals. Furthermore, increasing the relative amounts of 18:2(n-6) in the diet (SO group) led to an increased incorporation of linoleic acid, 18:2(n-6) in MC phospholipids when compared to both other dietary groups. The changes in MC phospholipid fatty acid composition were (partly) reflected in the formation of prostanoids and hydroxy fatty acids upon stimulation with the calcium ionophore A23187. The decrease in arachidonic acid content in MC phospholipids of MO-fed rats resulted in a decreased formation of PGD2 when compared to both other groups. Also, the increased amounts of 18:2(n 6) in MC phospholipids of SO-fed rats resulted in an increased formation of 9- and 13-HODE upon stimulation. The results show that modifications in the fatty acid composition of the diet influences MC membrane fatty acid composition which ultimately results in changes in prostanoid and hydroxy fatty acid synthesis by MC upon stimulation with the calcium ionophore A23187. PMID- 8466943 TI - Stimulation of acyl-CoA:cholesterol acyltransferase activity by brefeldin A in macrophage J774 cells. AB - Brefeldin A (BFA), an inhibitor of secretory pathway, enhances incorporation of radiolabeled cholesterol and oleate into cholesteryl esters in cultured cells [12]. We studied the mechanism for this effect of BFA in the macrophage J774. When incubated with 2.7 microM BFA in the absence of lipoproteins, J774 cells synthesized and accumulated 1.5- to 4-fold more cholesteryl esters than did cells which received no BFA. BFA caused neither an elevation of cholesterol synthesis, inhibition of its secretion nor changes in cholesterol transport to plasma membrane, esterification of plasma membrane cholesterol and cholesteryl ester hydrolysis. Acyl-CoA:cholesterol acyltransferase (ACAT) activity in microsomes from BFA-treated cells was 1.5- to 1.8-fold higher than that from control cells. The effect of BFA was diminished by treatment with low temperature, which is known to abolish BFA effect on Golgi formation. PMID- 8466944 TI - Intestinal perfusion of beta-carotene in the ferret raises retinoic acid level in portal blood. AB - To determine whether beta-carotene (beta-C) can serve as a source of intestinally derived retinoic acid (RA), either 15,15'-[14C]beta-C or unlabeled beta-C was perfused through 30 cm jejunal segments of ferrets in vivo. Portal vein blood was sampled periodically via an indwelling catheter. RA was identified in portal blood by comparing retention times in HPLC, by UV absorption, and by derivatization (methylation) and subsequent GC-MS analysis. The RA concentration in the portal blood increased 3-fold with perfusion of beta-C (P < 0.05), and remained at 18 nmol/L during the perfusion of beta-C. The single peak of RA in HPLC was shown to consist of four separate peaks by GC-MS, which may be cis-trans isomers of RA. The concentration of RA in portal blood returned to the initial level (5 nmol/L) after a 2 h period of intestinal perfusion with 5% dextrose. Retinyl ester concentration in portal blood did not change before or after the perfusion, whereas retinol decreased significantly during the perfusion of beta C. This study clearly indicates that a considerable quantity and number of polar metabolites, including RA, are formed from beta-C in the ferret intestine which are transported via the portal vein to the liver. PMID- 8466945 TI - Arachidonic acid metabolism of rat peritoneal macrophages after passive sensitization and allergen challenge. AB - The aim of our work was to evaluate the effect of passive sensitization of rat peritoneal macrophages (treatment of cells by an anti-ovalbumin IgE-rich serum) on arachidonic acid (AA) metabolism and the impact of specific antigen (ovalbumin) on this process. Compared to a control treatment without serum, the atopic serum and a serum without IgE, used on [3H]AA-labeled macrophages, increased cyclooxygenase and lipoxygenase eicosanoid production. Sera, used prior to [3H]AA incorporation, induced a decrease of 3H-labeled membrane phospholipids and an increase of lipoxygenase metabolites in the [3H]AA incorporation medium. To establish if the serum-induced catabolism of AA differed according to whether it was externally added to the culture medium or incorporated into membrane phospholipids, we studied the eicosanoid secretion of [3H]AA-prelabeled macrophages, treated by the serum and incubated with [14C]AA. It was confirmed that phospholipid-incorporated AA was catabolised following the cyclooxygenase and lipoxygenase pathways and external AA preferentially following the lipoxygenase pathway. The allergen increased the eicosanoid formation of passively sensitized macrophages but not that of cells treated by the serum without IgE. Our data suggest that changes occurring in passive sensitization, on AA mobilization from membrane phospholipids and on AA catabolism, induced by the serum, are independent of IgE and must be taken into consideration on interpreting the allergen effect. PMID- 8466946 TI - The hypocholesterolemic effect of sulfur-substituted fatty acid analogues in rats fed a high carbohydrate diet. AB - Sulfur-substituted fatty acid analogues have been administered to rats fed a high carbohydrate diet, and the effect on plasma and hepatic lipid metabolism was investigated. Two of the analogues studied, 3-thiadicarboxylic acid and tetradecylthioacetic acid, reduced the plasma cholesterol level significantly, whereas the effect on plasma triacylglycerol level was only marginal. 3 Thiadicarboxylic acid was the most potent, decreasing the cholesterol level faster and at a lower dose than tetradecylthioacetic acid. The relative effects on plasma cholesterol and triacylglycerol levels were different from what have been observed in rats fed a conventional pellet diet. Tetradecylthiopropionic acid had no hypocholesterolemic effect. The activities of three lipogenic enzymes: ATP-citrate lyase, acetyl-CoA carboxylase and fatty acid synthase was measured. The two hypocholesterolemic analogues reduced the activities of these enzymes in a coordinated manner. The enzyme activities was found to correlate with the the plasma cholesterol level, indicating a coordinated regulation of these enzymes and cholesterol synthesis or secretion. The effect on two enzymes involved in cholesterol metabolism was also studied. The activity of acyl CoA:cholesterol acyltransferase (ACAT) was reduced by the two hypocholesterolemic analogues, in contrast to the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, which tended to increase. The cholesterol lowering effect of 3 thiadicarboxylic acid and tetradecylthioacetic acid can probably be ascribed to diminished cholesterol synthesis due to a reduced availability of acetyl-CoA. A reduction in the esterification of hepatic cholesterol may be a contributing factor. PMID- 8466947 TI - Stimulation of mycolic acid biosynthesis by incorporation of cis-tetracos-5-enoic acid in a cell-wall preparation from Mycobacterium smegmatis. AB - Mycolic acids are high molecular weight hydroxy fatty acids which are a covalently linked part of the cell wall structure of all mycobacteria and their biosynthetic pathways offer potential drug targets. Three good candidates, cis tetracos-5-enoic acid and R or S trans-6-methyl-tetracos-4-enoic acids, for the key initial intermediates where mycolic acid biosynthesis might diverge from other metabolic pathways, were tested as possible substrates. A cell-wall preparation from Mycobacterium smegmatis, capable of mycolic acid synthesis, was developed to investigate the possible incorporation of these, and other 16 to 24 carbon acids into mycolic acids. The wall preparations were extracted with hexane and suspended in hexane/water (7:1, v/v), and in this low-water assay, only one of these acids, cis-tetracos-5-enoic acid, stimulated the incorporation of radioactive label from [1-14C]acetate into alpha- and alpha'-mycolic acids. The extraction method used did, however, abolish some enzyme activity and mycolic acid biosynthesis was not completely restored by cis-tetracos-5-enoate. The two methyl-branched acids did not enhance the amount of label in epoxymycolic acids. An initial key intermediate in the synthesis of alpha- and alpha'-mycolic acids has therefore been positively identified for the first time; intermediates in the initial stages of the biosynthesis of oxygenated mycolic acids such as epoxymycolates remain to be defined. PMID- 8466948 TI - Acylcarnitine formation and fatty acid oxidation in hepatocytes from rats treated with tetradecylthioacetic acid (a 3-thia fatty acid). AB - In livers of rats fed a single morning dose of 100 mg tetradecylthioacetic acid (TTA) total long-chain acyl-CoA increased significantly to 3 times control levels within 6 h, then the level declined almost to control value within the next morning. Hepatic malonyl-CoA was reduced 75% 6 h after TTA treatment. From 6 to 24 h malonyl-CoA increased about 10-fold to about 3 times that of controls. Paradoxically there was nearly a 2-fold higher oxidation of both [1-14C]palmitic acid (0.5 mM) and [1-14C]oleic acid (0.5 mM) in hepatocytes isolated from rats 24 h after TTA treatment compared to controls. After 6 h, when malonyl-CoA was at a minimum in vivo, fatty acid oxidation in cells was not increased. Acylcarnitine formation in digitonin permeabilized hepatocytes isolated 24 h after administration of TTA was increased both in the absence and in the presence of malonyl-CoA. At 24 h peroxisomal palmitoyl-CoA oxidase activity was not increased. The results suggest that an increased CPT activity and increased acylcarnitine formation in the presence of malonyl-CoA is a delayed response to increased acyl-CoA levels. Furthermore, in hepatocytes isolated after 24 h incorporation of [1-14C]oleic acid into triacylglycerols was significantly reduced. The data show that in hepatocytes isolated from rats 24 h after administration of a single dose of TTA, there is a diversion of hepatic acyl-CoA from synthesis of triacylglycerols into beta-oxidation in the mitochondria. PMID- 8466949 TI - Dependence of the plasma triacylglycerol-lowering effect of fish oil on insulin replacement in streptozotocin diabetic rats. AB - Streptozotocin diabetic rats, with and without insulin replacement, and sham injected controls were fed a high-fat (30% of energy) menhaden oil (MO) or corn oil (CO) diet for 2 weeks. After an overnight fast, plasma and livers were collected for analysis of insulin, glucose, triacylglycerol, cholesterol and glucose-6-phosphate dehydrogenase activity. Streptozotocin treatment resulted in decreased plasma insulin and elevated glucose. MO-feeding to insulin-replaced diabetic rats resulted in higher insulin and lower glucose levels compared to the respective CO-fed rats, suggesting decreased hepatic insulin extraction and greater peripheral utilization of glucose with MO. Plasma triacylglycerol and cholesterol, and hepatic glucose-6-phosphate dehydrogenase activity were reduced in MO-fed vs. CO-fed control rats. These effects of MO were prevented in the diabetic rats but were restored by insulin replacement. We conclude from our data that the presence of insulin is required to observe at least some of the effects of fish oil (FO). To explain our observations we propose that many of the effects of FO on hepatic metabolism are mediated by an inhibition of insulin action in the liver, thus providing a possible central mechanism for the regulation of hepatic lipid metabolism by dietary FO. PMID- 8466950 TI - Lysosomal phosphatidylcholine: bis(monoacylglycero)phosphate acyltransferase: specificity for the sn-1 fatty acid of the donor and co-purification with phospholipase A1. AB - Positional specificities in donor and acceptor phospholipids of the lysosomal phosphatidylcholine: bis(monoacylglycero)phosphate acyltransferase have been determined. Comparison of the transfer of labelled fatty acid from sn-1 [14C]acyl and sn-2 [14C]acylphosphatidylcholines by extracts of rat liver lysosomes revealed that fatty acids in the sn-1 position were exclusively transferred. Degradation of the acylphosphatidylglycerol product by Rhizopus arrhizus lipase, highly specific for fatty acids esterified to sn-1 or sn-3 positions, indicated that sn-1 or sn-3 rather than sn-2 positions had been acylated. Assays of phospholipase A1, phosphatidylcholine: bis(monoacylglycero)phosphate acyltransferase, the conversion of lysophosphatidylglycerol to bis(monoacylglycero)phosphate and phospholipase A2 were performed at various steps in the purification of lysosomal phospholipase A1. After the penultimate step of chromatofocusing, there was a 1086-fold increase of phospholipase A1 specific activity over the homogenate and this was accompanied by a 11 998-fold increase of phosphatidylcholine: bis(monoacylglycero)phosphate acyltransferase specific activity. A second preparation carried through to the final step of gel filtration retained a similar ratio of acyltransferase activity. On the other hand, specific activities of phospholipase A2 and of the conversion of lysophosphatidylglycerol to bis(monoacylglycero)phosphate increased to the step where enzyme was solubilized from lysosomes, but were lost from later steps. These findings suggest that phosphatidylcholine: bis(monoacylglycero)phosphate acyltransferase is catalyzed by lysosomal phospholipase A1. The site of acylation in the bis(monoacylglycero)phosphate acceptor appears to be either sn-1 or sn-3. Since the lysosomal extracts did not catalyze the transacylation of phosphatidylglycerol, we conclude that the formation of acylphosphatidylglycerol in lysosomes requires the sequential acylation of lysophosphatidylglycerol to form bis(monoacylglycero)phosphate by an unidentified enzymatic mechanism followed by a transacylation of bis(monoacylglycero)phosphate in either sn-1 or sn-3 position to form acylphosphatidylglycerol which is catalyzed by phospholipase A1. PMID- 8466951 TI - A comparative study of low-density lipoprotein interaction with glycosaminoglycans. AB - The association between low-density lipoprotein (LDL) and a series of well characterized dermatan and chondroitin sulfates has been investigated by means of the fluorescence anisotropy technique with competition experiments using a fluorescein-labeled high LDL-affinity heparin fraction as a reference. Preparations of glycosaminoglycan (GAG) with sulfation degrees varying over a wide range, as obtained by fractionation or by chemical modification, were chosen for this study. The influence of chain length, which had been found sizeable in a former study of heparin affinity for LDL, was taken into account with an empirical correction of dissociation constants. After this correction, a linear relationship was found between the logarithm of dissociation constants and the number of sulfate groups per disaccharide unit, ns, both for dermatan and chondroitin sulfates, and for heparins. At comparable ns values, however, dermatan sulfates and heparins, which contain L-iduronic acid in their backbone, show higher LDL-affinity than chondroitin sulfates, which contain only D glucuronic acid. Though confirming a non-specific, predominantly electrostatic interaction between GAGs and LDL, these results indicate modulation of LDL affinity by the polysaccharide backbone. PMID- 8466952 TI - A novel member of the lipocalin superfamily: tammar wallaby late-lactation protein. AB - The finding that tammar wallaby late-lactation protein is linked to beta lactoglobulin prompted a search of current GenPeptide and NBRF-PIR protein databases for sequence similarities to late-lactation protein. Similarities were found to von Ebner's gland protein and other members of the lipocalin superfamily of proteins. A conservative replacement of Trp with Tyr suggests that late lactation protein may represent an unusual member of this protein superfamily. PMID- 8466953 TI - Effect of fluvastatin sodium (XU62-320), a new inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A reductase, on the induction of low-density lipoprotein receptor in HepG2 cells. AB - The effect of fluvastatin sodium (XU62-320), a new type of inhibitor of 3-hydroxy 3-methylglutaryl coenzyme A, on the induction of LDL receptor in the human liver derived cell line HepG2 was investigated. Fluvastatin sodium produced marked inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and induction of LDL receptor on HepG2 cells at a concentration of 0.1-1.0 microM. These results suggest that fluvastatin sodium has potential for use as a strong plasma cholesterol-lowering drug. PMID- 8466954 TI - Strategies for peak-purity assessment in liquid chromatography. AB - One of the key requirements for the validation of chromatographic methods is to determine the purity of a chromatographic peak. Statistical modelling of the chromatographic process suggests that overlapping components are highly probable in a chromatogram. Hence extensive efforts have been directed at the development of sensitive, reliable and robust methods to assess peak purity. This is especially the case in the pharmaceutical industry, where liquid chromatography (LC) is widely utilized and the demands on method validation are justifiably high. On-line multiwavelength absorptiometric detection is often used to generate the additional data required to facilitate peak-purity assessment in LC. This approach, using photodiode-array technology, is directly compatible with the aqueous-based reversed-phase LC solvents used extensively in drug analysis. Consequently, this work highlights many of the peak-purity algorithms, which may be applied using LC with diode-array detection. The relative merits of the individual techniques are discussed, and a rationale is developed for their application. PMID- 8466955 TI - Determination of thiol-containing drugs by chemiluminescence-flow injection analysis. AB - A flow injection analysis procedure with chemiluminescence detection for the determination of both thiol-containing drugs and the amino acid cysteine is described. Procedures are based on the inhibition by the drugs of the chemiluminescence generated in the copper-catalysed oxidation of luminol by hydrogen peroxide. The proposed methods were applied to the determination of cysteine, N-acetylcysteine, penicillamine, 2-mercaptopropionylglycine and thiouracil in pharmaceuticals. PMID- 8466956 TI - Analysis of biological fluids using 600 MHz proton NMR spectroscopy: application of homonuclear two-dimensional J-resolved spectroscopy to urine and blood plasma for spectral simplification and assignment. AB - The application of 600 MHz two-dimensional J-resolved 1H NMR spectroscopy (JRES) to the analysis of human urine and blood plasma is demonstrated. This method when applied at very high field gives a rapid means of simplifying and aiding the assignment of highly overlapped resonances of minor metabolites in biofluids. Using this approach, mixtures of drug and endogenous metabolites were identified in untreated urine samples, the signals of which were extensively overlapped in single pulse 600 MHz spectra. For untreated blood plasma samples the JRES experiment was also effective for the selective attenuation of signals from the plasma proteins thus revealing strong well-resolved signals from the low molecular weight components. For the first time it was shown to be possible to assign in detail the spectra region from 3 to 4 ppm in blood plasma, including the complete assignment of the signals from alpha- and beta-glucose. JRES spectra of plasma were much easier to interpret and had a much higher information content than equivalent one-dimensional Hahn spin-echo spectra, thus aiding the identification of non protein-bound low molecular weight metabolites in plasma. PMID- 8466957 TI - Micellar acid-base potentiometric titrations of weak acidic and/or insoluble drugs. AB - The effect of various surfactants [the cationics cetyl trimethyl ammonium bromide (CTAB) and cetyl pyridinium chloride (CPC), the anionic sodium dodecyl sulphate (SDS), and the nonionic polysorbate 80 (Tween 80)] on the solubility and ionization constant of some sparingly soluble weak acids of pharmaceutical interest was studied. Benzoic acid (and its 3-methyl-, 3-nitro-, and 4-tert-butyl derivatives), acetylsalicylic acid, naproxen and iopanoic acid were chosen as model examples. Precise and accurate acid-base titrations in micellar systems were made feasible using a microcomputer-controlled titrator. The response curve, response time and potential drift of the glass electrode in the micellar systems were examined. The cationics CTAB and CPC were found to increase considerably the ionization constant of the weak acids (delta pKa ranged from -0.21 to -3.57), while the anionic SDS showed negligible effect and the nonionic Tween 80 generally decreased the ionization constants. The solubility of the acids in aqueous micellar and acidified micellar solutions was studied spectrophotometrically and it was found increased in all cases. Acetylsalicylic acid, naproxen, benzoic acid and iopanoic acid could be easily determined in raw material and some of them in pharmaceutical preparations by direct titration in CTAB-micellar system instead of using the traditional non-aqueous or back titrimetry. Precisions of 0.3-4.3% RSD and good correlation with the official tedious methods were obtained. The interference study of some excipients showed that a preliminary test should be carried out before the assay of formulations. PMID- 8466958 TI - Pharmacokinetics of cyclosporin A during pregnancy; monitoring of treatment and specific assays of cyclosporin, based on five liver transplant patients. AB - Very little information is available concerning the pharmacokinetic behaviour and monitoring of cyclosporin A (CsA) during pregnancy, notably after liver transplant. Monitoring of blood levels of CsA is considered to be one of the best tools for evaluation of the efficacy of immunosuppressant treatment. The aim of this study was to bring together new information concerning pregnant women receiving immunosuppressant treatment with CsA and, in view of the special pathophysiological status of such patients, to compare pharmacokinetic profiles of changes in blood levels of CsA and of the combination of CsA plus metabolites. Specific (CsA-S kit) and a new non-specific (CsA-NS kit) assays of CsA were carried out in five hospitalized pregnant patients who had received liver transplants between the 6th and the 41st weeks of amenorrhea. The results of five cases investigated lead to the following conclusions: (1) The pharmacokinetic behaviour of native CsA in the pregnant woman between the 6th and 41st weeks of amenorrhea suggests no systemic accumulation nor any radical need for changes in dosage schedule as compared with a non-pregnant patient. (2) Monitoring based upon simultaneous use of the CsA-NS and CsA-S kits may be a source of analytical bias and hence confusion for the physician. (3) Determination of an experimental CsA-NS/CsA-S accumulation ratio (based upon analysis of single concentrations or processing of AUCs) is of interest only if specific assays involve not only CsA itself but also its principal metabolites. (4) Monitoring based upon single measurements of residual CsA levels only, is necessary and adequate. Furthermore, such an approach is less costly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466959 TI - Chloroisothiocyanatoquinolines as fluorogenic derivatizing agents for primary and secondary amines. AB - Two new prechromatographic LC fluorogenic derivatizing agents, 2- and 4-chloro-3 isothiocyanatoquinoline (4 and 5) have been synthesized and shown to react smoothly with primary and secondary amines to produce fluorescent thiazoloquinolines. Compounds 4 and 5 hydrolyse in aqueous base and the rates of this reaction compared with the rates of derivatizations with amino acids indicate that the hydrolysis reaction interferes with derivatization when UV detection is used. The kinetics of derivatization with ordinary amines indicate that this reaction is quite facile, although less nucleophilic amines, e.g. aniline, react slowly. The pKas for first protonations indicate that derivatives of 4 would be unprotonated and those of 5 would be protonated with typical RP-LC mobile phases. The Stokes shift for protonated derivatives of 5 is nearly 200 nm. The excess of unreacted derivatizing reagent interferes with UV detection of some analytes; but when fluorescence detection is used this excess produces only a small negative peak. With fluorescence detection the sensitivity of this method is about 0.8 microM at S/N of 2, and the response of peak height to concentration is linear over at least two decades of concentration. PMID- 8466960 TI - Microbore liquid chromatography with electrochemical detection for the control of phenolic antioxidants in drugs and foods. AB - Antioxidants are added to foods and drugs to inhibit their oxidation. As these additives are somewhat toxic, it is necessary to control the amount added to any food or drug. Liquid chromatography (LC) is a powerful tool for this purpose. Many antioxidants are electroactive molecules which enables the advantages of electrochemical detection or selectivity and sensitivity to be realized. The interest of analysts in microbore LC arises from the low mobile phase volumetric flow rates involved, the reduced on-column samples together with reduced chromatographic dilution and high efficiency. Coupling of microbore LC with electrochemical detection adds another advantage: the decrease of electrode ageing. The problem of extra-column band broadening with microbore column is discussed in the present communication. A micro LC-electrochemical detection system is constructed and tested using catecholamines. The limit of detection (LOD) for noradrenaline using a 0.7 mm bore column is found to be 0.1 pg injected in 0.2 microliter (0.6 femtomoles). Three phenolic antioxidants are studied: tert butyl-p-hydroxyanisole (BHA), di-tert-butyl-hydroxytoluene (BHT) and n-propyl gallate (3,4,5-trimethoxybenzoic acid propyl ester). The dynamic range is four orders of magnitude with LODs down to 0.1 femtomoles (20 fg injected) with a 0.3 mm bore column. No electrode response change is observed after 60 injections of 3 ng BHA over 6 days. Antioxidants are determined in different pharmaceutical preparations and foodstuffs (chewing gums, dried potato flakes). The agreement between the manufacturer stated concentrations and observed results is found to be satisfactory. PMID- 8466961 TI - Optimization of the separation of salbutamol and its decomposition products by liquid chromatography with diode-array detection. AB - A high-performance liquid chromatographic (HPLC) method based on diode-array detection is developed and optimized for stability studies on salbutamol. In establishing the method, the effects of mobile phase constituents (buffers, buffer concentration, pH, modifiers, organic solvents, ion-pair reagents) upon the resolution of salbutamol and its degradation products are studied. The optimum method involves the use of a LiChrosorb RP-18 column with a one-step gradient elution with acetonitrile-sodium dihydrogen phosphate (40 mM) triethylamine (5.74 mM) (pH 3.0). The acetonitrile content is increased from 4 to 9% after 6 min. PMID- 8466962 TI - Sensitive determination of 1,1'-ethylidenebis(L-tryptophan) in L-tryptophan by gradient HPLC with fluorimetric detection. PMID- 8466963 TI - E. P. Pope Memorial Award to Dr. Anthony Gallina. PMID- 8466964 TI - Pleuropneumonia in Missouri swine. PMID- 8466965 TI - Naturally occurring systemic anaphylactic and anaphylactoid reactions in four groups of pigs injected with commercially available bacterins. PMID- 8466966 TI - Listerial abortion in a llama. PMID- 8466967 TI - Septicemic Enterococcus infection in an adult llama. PMID- 8466968 TI - Yersinia pseudotuberculosis bovine abortion. PMID- 8466969 TI - Clostridial enteritis in red lories (Eos bornea). PMID- 8466970 TI - Small intestinal Chlamydia infection in piglets. PMID- 8466971 TI - Multicentric lymphosarcoma in a llama. PMID- 8466972 TI - Echinococcus granulosus hydatid cysts in the livers of two horses. PMID- 8466973 TI - Vertebral angiosarcoma in a horse. PMID- 8466974 TI - Investigation of selenium sources associated with chronic selenosis in horses of western Iowa. PMID- 8466975 TI - The effect of formalin fixation on the concentration of selenium in porcine liver. PMID- 8466976 TI - Hepatogenous photosensitization in cattle fed a grass hay. PMID- 8466977 TI - Detection of antigenemia by enzyme-linked immunosorbent assay in horses with experimental Ehrlichia risticii infection. AB - Four horses were inoculated with Ehrlichia risticii contained in either infected murine P388 D1 cells or heparinized blood from an infected horse. All 4 horses produced serum antibody, plasma antigen, and clinical signs of the disease. An enzyme-linked immunosorbent assay was used to detect antibody in the serum and was also used in conjunction with an anti-E. risticii monoclonal antibody to detect antigenemia. These laboratory and clinical findings were correlated to determine the efficiency of the antigen detection method for discerning E. risticii infection. PMID- 8466978 TI - Detection of humoral antigen and antibody by enzyme-linked immunosorbent assay in horses with experimentally induced Ehrlichia equi infection. AB - An enzyme-linked immunosorbent assay (ELISA) was used to detect antigen in plasma and antibody in serum of 3 horses inoculated with Ehrlichia equi. Clinical signs, including rectal temperature, were correlated with the antigen and antibody detection. ELISA was very efficient in detection of serum antibody. Antigen detection using monoclonal antibodies to E. equi and ELISA should be considered as a diagnostic method. PMID- 8466979 TI - Detection of Eperythrozoon suis using the polymerase chain reaction. AB - Eperythrozoon suis is an extracellular red blood cell parasite that causes icteroanemia in acutely ill pigs and a variety of syndromes in chronically infected pigs. Current techniques to detect E. suis infection are limited by variability of parasitemias and antibody responses in infected animals. The polymerase chain reaction (PCR) was investigated to determine its potential as a means of detecting E. suis infection in pigs. With DNA samples extracted from either purified E. suis organisms or E. suis-infected pig blood, PCR produced an amplification product 492 base pairs in length. This amplification product hybridized successfully with the fragment of the DNA probe from which the primer sequences had been selected. Sensitivity studies indicated that the PCR protocol was capable of amplifying total genomic E. suis DNA in quantities as low as 450 pg. When PCR was used with DNA from blood samples from a splenectomized pig that had been infected with E. suis, amplification products were detectable as early as 24 hours postinfection. This preliminary analysis indicates that PCR shows promise as a means of efficiently detecting E. suis infection in pigs. PMID- 8466980 TI - Preliminary characterization of a pleomorphic gram-negative rod associated with avian respiratory disease. AB - An unidentified, pleomorphic, gram-negative rod (PGNR) bacterium has been isolated from domestic fowl with respiratory disease. The PGNR was isolated in 5% of turkey accessions and 3% of chicken accessions, primarily from the respiratory tract. Preliminary characterization of this organism included reviewing accession records, conducting cultural and biochemical tests, and analyzing cellular fatty acids. The PGNR was also compared with other bacteria capable of inhabiting the avian respiratory system. Biochemical and cellular fatty acid analysis failed to identify the organism, however all 14 isolates were similar. PMID- 8466981 TI - Reproducibility of a commercial enzyme-linked immunosorbent assay for bovine paratuberculosis among eight laboratories. AB - Interlaboratory reproducibility of an absorbed enzyme-linked immunosorbent assay (ELISA) kit for detection of bovine serum antibodies to Mycobacterium paratuberculosis was evaluated. A panel of 30 bovine sera (15 positives and 15 negatives) was tested in triplicate microtiter wells on each of 2 days at 8 different laboratories. One laboratory had invalid results because of positive or negative serum control optical density (OD) readings beyond the acceptable range specified by the kit. The coefficient of variation (CV) for mean OD values was influenced by low ODs on test negative sera at 2 laboratories, thus the CVs on positive sera were considered a more representative measure of kit reproducibility. Between-well CVs averaged 6.7% +/- 2.8% (mean +/- standard deviation), and between-day CVs averaged 14.5% +/- 9.8% among the 7 laboratories with valid assays on the 15 positive sera. The OD values were converted to positive or negative classifications for each assay well, and the results were compared. Among 1,392 assays in 7 laboratories, 98.6% were in agreement. Eleven of 18 discrepant results were due to a sample that consistently gave OD values near the cutoff for a positive test. Exclusion of that serum from the analysis resulted in a 99.8% rate of agreement among laboratories. Results indicated that the absorbed ELISA kit provided reproducible results within and between laboratories. PMID- 8466982 TI - Etiology and pathology of equine placentitis. AB - Placentas from aborted, stillborn, and premature foals were examined during the 1988 and 1989 foaling seasons, and 236 of 954 (24.7%) had placentitis. Microorganisms associated with placentitis were isolated or demonstrated from 162 of 236 (68.6%) placentitis cases. Leptospira spp. and a nocardioform actinomycete were 2 important, newly emerging bacteria associated with equine placentitis. Major pathogens identified in decreasing order were Streptococcus zooepidemicus, Leptospira spp., Escherichia coli, a nocardioform actinomycete, fungi, Pseudomonas aeruginosa, Streptococcus equisimilis, Enterobacter agglomerans, Klebsiella pneumoniae, and alpha-hemolytic Streptococcus. Pathogens were not recovered in 64 cases (27.1%) and overgrowth by saprophytic bacteria was recorded in 10 cases (4.2%). Twenty-seven cases (16.6%) had mixed bacterial growth and 93 cases (57.4%) had bacteria cultured from both placenta and fetal organs. The majority of the placentitis cases caused by bacteria, with the exception of Leptospira spp. and the nocardioform actinomycete, occurred in 2 forms. One was acute, focal or diffuse; had an infiltration of neutrophils in the intervillous spaces or necrosis of chorionic villi; was associated with bacteremia; and frequently occurred in the placenta from fetuses expelled before or at midgestation. The other was observed from foals expelled at late gestation, was mostly chronic and focal or focally extensive, and occurred mostly at the cervical star area. Chronic placentitis was characterized by the presence of 1 or a combination of the following lesions: necrosis of chorionic villi, presence of eosinophilic amorphous material on the chorion, and infiltration of mononuclear inflammatory cells in the intervillous spaces, villous stroma, chorionic stroma, vascular layer, and allantois.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8466983 TI - Bacterial agents detected in a 10-year study of bovine abortions and stillbirths. AB - In a 10-year survey started in 1980, specimens from 8,995 bovine abortions and stillbirths were submitted to the South Dakota Animal Disease Research and Diagnostic Laboratory. Of these, 8,962 were suitable for some type of examination. Bacteria were determined to be the cause of 1,299 (14.49%). The 5 bacteria most commonly associated with bovine abortion or stillbirth were Actinomyces pyogenes, 378 (4.22%); Bacillus spp., 321 (3.58%); Listeria spp., 121 (1.35%); Escherichia coli, 98 (1.09%); and Leptospira interrogans, 79 (0.88%). Twelve other genera of bacteria were associated with > or = 10 abortions or stillbirths, and 12 more species were associated with < or = 10 abortions or stillbirths. PMID- 8466984 TI - Experimental equine leukoencephalomalacia, toxic hepatosis, and encephalopathy caused by corn naturally contaminated with fumonisins. AB - A study to evaluate the effects of dietary fumonisin B1 was conducted using 6 ponies (4 test and 2 control). A ration naturally contaminated with fumonisin B1 was fed in 3 phases: 1) 44 ppm fumonisin B1, 2) less than 1 ppm fumonisin B1, and 3) 88 ppm fumonisin B1. All ponies were monitored daily, weighed weekly, and limit fed at a rate of 0.8% body weight plus hay. Feed intake was measured daily, and a serum chemistry panel was completed once or twice weekly. Four to 7 days after initiation of the trial (Phase 1), all 4 test ponies had decreased feed consumption, and selected serum chemistry parameters were markedly elevated. On day 9, 1 pony died acutely with mild encephalopathy and hepatic necrosis. Another pony, euthanized on day 45, also had mild encephalopathy and hepatic necrosis. The remaining 2 test ponies continued the 44 ppm fumonisin B1 diet for 98 days. Phase 2 consisted of a diet with < 1 ppm fumonisin B1 for 120 days. During this phase, the serum chemistry values of the 2 ponies returned to normal. Following Phase 2, the 2 ponies were fed a diet containing 88 ppm fumonisin B1. After 75 days, 1 animal died of equine leukoencephalomalacia with mild hepatic necrosis. On day 78, the remaining pony was euthanized after showing distress; it also had leukoencephalomalacia and hepatic lesions. PMID- 8466987 TI - Naturally occurring selenosis in Wyoming. AB - A review of Wyoming State Veterinary Laboratory records for 1947-1987 revealed no substantiated cases of naturally occurring selenosis. However, older reports attributed thousands of animal deaths to selenium each year in this area. Beginning in August 1988, cases of suspected selenosis and selenium deficiency were solicited from veterinarians and producers by announcements in various statewide livestock publications. As of August 1991, 4 cases (all horses) of naturally occurring selenosis have been confirmed. Clinical signs were most often referable to epithelial damage, e.g., hoof lesions and loss of mane and tail. None involved neurologic signs. Sources of selenium included native range and grass hay. PMID- 8466985 TI - Fumonisin toxicity in turkey poults. AB - The effects of dietary fumonisin B1 were evaluated in young turkey poults. The experimental design consisted of 3 treatments, with 24 female turkey poults allotted randomly per treatment. Day-old poults were fed diets containing 0 mg (feed control), 100 mg, and 200 mg fumonisin B1/kg feed for 21 days. Body weight gains and efficiency of feed conversion decreased linearly with increasing dietary fumonisin. Liver, kidney, and pancreas weights increased linearly with increasing dietary fumonisin, and spleen and heart weights decreased. Serum aspartate aminotransferase levels increased with increasing dietary fumonisin, and serum cholesterol; alkaline phosphatase, mean cell volume, and mean cell hemoglobin all decreased. Biliary hyperplasia, hypertrophy of Kupffer's cells, thymic cortical atrophy, and moderate widening of the proliferating and degenerating hypertrophied zones of tibial physes were present in poults fed diets containing fumonisin B1. Results indicate that fumonisin B1, from Fusarium moniliforme culture material, is toxic in young poults, and the poult appears to be more sensitive to fumonisin than the broiler chick. PMID- 8466986 TI - Pathogenic studies and antigenic and sequence comparisons of A/equine/Alaska/1/91 (H3N8) influenza virus. AB - An influenza virus, A/equine/Alaska/1/91 (H3N8), was isolated from horses from Alaska with an acute respiratory infection. Pathogenic and serologic studies revealed that this virus is similar to previously isolated equine H3N8 influenza viruses. Antigenic analyses utilizing hemagglutination inhibition and neuraminidase inhibition assays indicated an antigenic drift from the prototype equine H3N8 influenza virus, A/equine/Miami/1/63. Partial sequence analysis of the A/equine/Alaska influenza virus indicated that each of 8 gene sequences are of equine origin. PMID- 8466988 TI - Equine protozoal myeloencephalitis: antigen analysis of cultured Sarcocystis neurona merozoites. AB - Antigens of cultured Sarcocystis neurona merozoites were examined using immunoblot analysis. Blotted proteins were probed with S. cruzi, S. muris, and S. neurona antisera produced in rabbits, S. fayeri (pre- and post-infection) and S. neurona (pre- and post-inoculation) sera produced in horses, immune sera from 7 histologically confirmed cases of equine protozoal myeloencephalitis (EPM), and pre-suckle serum from a newborn foal. Eight proteins, 70, 24, 23.5, 22.5, 13, 11, 10.5, and 10 Kd, were detected only by S. neurona antiserum and/or immune serum from EPM-affected horses. Equine sera were titered by the indirect immunofluorescent antibody (IFA) method using air-dried, cultured S. neurona merozoites. Anti-Sarcocystis IFA titers were found in horses with or without EPM. Serum titers did not correspond to the number of specific bands recognized on immunoblots. PMID- 8466990 TI - Serologic responses to the mallein test for glanders in solipeds. PMID- 8466989 TI - Poliomyelomalacia and ganglioneuritis in a horse with paralytic rabies. PMID- 8466991 TI - Clostridium difficile associated with typhlocolitis in an adult horse. PMID- 8466992 TI - [Physico-chemical compatibility of drugs with enteral nutrition]. AB - The physical and chemical compatibility of an enteral diet (standard Precitene) with a series of liquid preparations included in the hospital's formulary was evaluated. These preparations are included in the following groups: vitamins, antibiotics and chemotherapeutic drugs, analgesics, antiepileptic drugs, neuroleptics, bronchodilators, expectorants, antihistamines, immunosuppressors and short chain triglycerides. Phase separation, particle growth pH variation, osmolality increase and viscosity increase were studied. The results obtained indicate that the majority of the drugs studied are compatible from a physical and chemical point of view with the enteral diet used, at least during a 24 hour period, with the exception of those drugs which, because of their pH, acidify the mixture, causing problems of increased viscosity and particle growth, and of those liquid preparations of continuous oleous phase where phase separation is unavoidable. Lastly, a series of recommendations are given on cases where joint administration of drugs with enteral nutrition is suitable. PMID- 8466993 TI - [Nutritional parameters and morbimortality in clinical hospitalization]. AB - The prevalence of malnutrition in patients admitted to hospital in the region of Northwest Murcia and its repercussion on the morbidity rate and length of admission are studied. A protocol of nutritional evaluation according to the computer programme EDECAN-MED was applied, and the corresponding statistical treatment of data and results was done. We find that anthropometric data lack predictive value and that deterioration in the values for albumin, basal energy expenditure and nutritional prognostic index are associated with increased morbidity/mortality and prolongation of the length of hospital stay. The most valuable predictive datum of the length of hospital stay was the nutritional prognostic index, in spite of it being an index of surgical risk. PMID- 8466994 TI - [Control of the biological contamination index in total parenteral nutrition (TPN) preparations]. AB - Possible microbiological contamination of 1,107 mixtures of TPN made up in the Pharmacy Department of the General Hospital of Albacete in 1991 are studied. In this department, the TPN mixtures are prepared in a horizontal laminar flow chamber, under the aseptic conditions included in the literature. When we come to evaluate the contamination index of these preparations, we have to take the increase in the work load on days before public holidays into account. We observe that, when the preparation norms are rigorously followed, no significant contamination is produced, even on days when the number of mixtures to be made up is higher. PMID- 8466995 TI - [Possible mistakes in the interpretation of commercial nitrogenous solutions]. PMID- 8466996 TI - [Plasma aminogram in critical patients]. AB - This study of the plasma aminogram was done on 35 patients with a moderate to high level of stress and/or sepsis. For the criteria of illness, the SAPS (Simplified Acute Physiological Score) was used on their admission to the intensive Care Unit, and the diagnosis of sepsis was established according to the criteria of Jacobs and Boone. The stress level was calculated according to Bistrian. The plasma aminogram was determined with High Resolution Liquid Chromatography. The plasma samples were taken while nutrient units containing what is considered a standard solution of amino acids were infused. The eight essential amino acids (EAA) and 10 non-essential were quantified. The ratio of ramified to aromatic amino acids (RAA/AAA) was calculated by Fisher's criteria. An increase in AAA (phenylalanine, p < 0.001, and tyrosine, NS) and sulphur containing amino acids (methionine, p < 0.001) was found. The RAA were within normal ranges (valine) or increased (leucine, p < 0.001 and isoleucine, p < 0.001). The RAA/AAA ratio was reduced, p < 0.0001. Glycine was increased, p < 0.0001 and alanine reduced, p < 0.05. Glutamine and glutamic acid were reduced, p < 0.0001 and p < 0.01 as was arginine, p < 0.001. No difference was found in the total concentration of AA. The results confirm the standard plasma aminogram described in situations of metabolic stress and/or sepsis. PMID- 8466997 TI - [Nutritional status of patients undergoing digestive surgery]. AB - A retrospective study of 102 patients, analysing the incidence of malnutrition, was done in the Digestive Surgery Department of the Queen Sophia University Hospital, Cordoba. Patients were subjected to a protocol of nutritional evaluation to find out their nutritional condition and type and degree of malnutrition. The high incidence of malnutrition sufferers (> 80%) at the time of hospital admission was confirmed, being more noticeable in neoplastic patients. PMID- 8466998 TI - [Methods for quality control in parenteral nutrition. III: application of the program to therapeutic results]. AB - Therapeutic results of parenteral nutrition are evaluated by clinical nutritional benefits and by its safety with respect to the potential complications related to the method of administration and its inherent metabolic complications. In this context, a quality control programme was applied retrospectively to 148 patients and was evaluated according to the following indicators: a) PN suspension; b) a nutritional evaluation on termination of the parenteral nutrition; c) catheters inserted; d) mechanical complications; e) septic complications; f) routine controls; g) complete controls, and h) biochemical changes. The compliance percentages obtained were 92.8, 100, 85.1, 81.4, 84.9, 60.0, 33.1 and 43.8 respectively. These results allow us to see, for the first time, the profile of therapeutic quality in patients with parenteral nutrition. Likewise, it constitutes an obligatory methodology of intrahospital reference for continued improvement of parenteral nutrition received by patients admitted to this hospital. PMID- 8466999 TI - Self-employed nursing. PMID- 8467000 TI - Profile of a self-employed nurse. PMID- 8467001 TI - Making it on her own. Interview by Laura Brown. PMID- 8467002 TI - Marketing dilemmas for health care providers. PMID- 8467003 TI - Nursing a difficult patient. PMID- 8467004 TI - Putting research into practice. PMID- 8467005 TI - Pioneering spirit lives on. PMID- 8467006 TI - Caring for a chemically-dependent colleague. PMID- 8467007 TI - Consent to health care. PMID- 8467008 TI - A self-directed approach to health care reform. PMID- 8467009 TI - Back injury may end your career. PMID- 8467010 TI - Different effect of Intralipid and triacylglycerol rich lipoproteins on the Kodak Ektachem serum cholesterol determination. AB - We documented the quantitative effects of lipaemia on cholesterol recovery on a Kodak Ektachem 700 XRC analyser (Rochester, NY, USA) in comparison with a Hitachi 717 analyser (Boehringer, Mannheim, Germany). Using the linear ranges of the analysers, we compared the effects of adding Intralipid and of adding high concentrations of native Very-Low-Density-Lipoproteins and/or chylomicrons. Our data demonstrate less than 10% bias for the Kodak cholesterol determination in an Intralipid dilution series prepared according to M. R. Glick and coworkers (e.g. Clin. Chem. 33 (1987) 1453-1458). However, in a hypertriglyceridaemic dilution series (theoretical cholesterol concentrations ranged from 5.2 to 15.5 mmol/l) the Kodak cholesterol recovery fraction decreased from 0.88 to 0.58 when the triacylglycerol concentration increased from 5.64 mmol/l to 38.35 mmol/l. In contrast, the cholesterol recoveries on the Hitachi analyser were complete for both approaches. We conclude that the lipaemia effect on the Kodak cholesterol determination is not adequately reflected by addition of Intralipid, because the Kodak cholesterol determination is more prone to interference by turbidity when triacylglycerols are presented as native serum lipoproteins, especially as chylomicrons. PMID- 8467011 TI - Acetylation phenotypes and biological variation in a French Caucasian population. AB - Factors affecting the caffeine acetylation phenotype were investigated in a French Caucasian population of 150 unrelated supposedly healthy subjects, aged 18 to 63 years. This population, including 75 men and 75 women, was used to determine whether the acetylation polymorphism is related to environmental influences such as smoking habits, intake of alcohol, use of oral contraceptives, use of certain drugs. The acetylation phenotype was assessed from the molar ratio of two caffeine metabolites: 5-acetylamino-6-formylamino-3-methyluracil/1 methylxanthine. For values less than 0.85, the subjects were classified as poor acetylators (frequency, mean +/- SD: 61.3 +/- 7.9%) in this study. Dose recoveries of 5-acetylamino-6-formylamino-3-methyluracil (mean +/- SD) were 1.26 +/- 0.85% and 3.58 +/- 1.64% in slow and rapid acetylators, respectively. The recovery (mean +/- SD) of 1-methylxanthine in the 3 hour-urine was 2.86 +/- 1.51% in slow acetylators and 2.36 +/- 1.27% in rapid acetylators. The mean value (and SD) of the molar ratio was 0.437 (0.177) and 1.669 (0.651) for slow and rapid acetylators. Three other metabolite ratios can also provide an acetylation index: 5-acetylamino-6-formylamino-3-methyluracil/5-acetylamino-6-formylamino-3 - methyluracil + 1-methylxanthine + 1-methyluric acid; 5-acetylamino-6-formylamino 3-methyluracil/1-methylxanthine + 1-methyluric acid + 1,7-dimethyluric acid; and 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine + 1-methyluric acid + 1,7-dimethyluric acid + 1,7-dimethylxanthine with a bimodal distribution for the former and a trimodal distribution for the two latter ratios, both showing about 95% concordance with the 5-acetylamino-6-formylamino-3-methyluracil/1 methylxanthine ratio. Age did not influence the excretion of caffeine and its five major metabolites. A marked influence of sex was observed only on the unchanged caffeine excretion, and the effect was greater in slow acetylators than in rapid acetylators. The 5-acetylamino-6-formylamino-3-methyluracil excretion was about three times higher in rapid acetylators than in slow acetylators in both sexes. PMID- 8467012 TI - Anomalous tumour marker concentrations in renal transplant patients. AB - Serial serum determinations of the tumour associated antigens carcinoembryonic antigen, tissue polypeptide antigen, CA 19-9, CA 15-3 and CA 125 were performed on 70 patients who were undergoing, or had undergone renal transplantation. The period of observation ranged from 4 days pre-operative to 708 days post operative, although daily monitoring was usually carried out during the first 14 35 days post-operatively. With the exception of tissue polypeptide antigen, which was analysed with an immunoluminometric assay, all analytes were measured with the Enzymun-Test System ES-300 using immunoenzymometric assays with colorimetric determination. The interassay coefficients of variation were less than 5% for the immunoenzymometric assays and 8.7% for tissue polypeptide antigen, all values being derived from 20 consecutive assays. Only 8/70 patients with no complications showed normal concentrations for all five analytes. 6/79 patients showed parallel changes of at least three markers. 7/70 patients had transient elevations of at least one marker, whereas 25/70 patients had a continual elevation of CA 125, 9/70 CA 19-9 and 1/70 CA 15-3, although no patient showed evidence of disease. Two patients, each with 2 rejection episodes, showed daily fluctuations up to 100% for all markers, with the exception of carcinoembryonic antigen. There was no correlation between elevated tumour markers and cytomegalovirus infection. PMID- 8467013 TI - Preferential inhibition of LDL oxidation by the all-trans isomer of beta-carotene in comparison with 9-cis beta-carotene. AB - The synthetic all-trans isomer of beta-carotene was recently shown to possess antioxidant properties towards the formation of oxidized low density lipoprotein. In the present study, the binding of the all-trans and the 9-cis isomers of beta carotene to plasma lipoproteins was investigated, and the effect of these isomers on the susceptibility of plasma lipoprotein to lipid peroxidation and on macrophage uptake of oxidized LDL were studied. Both the synthetic all-trans isomer of beta-carotene and the natural beta-carotene from the algae Dunaliella Bardawil [which is composed of the all-trans (70%) and the 9-cis (30%) isomers], were found to bind similarly to all plasma lipoproteins, following the incubation of beta-carotene with purified lipoproteins or with whole plasma. Incubation of the beta-carotene isomers with whole plasma, followed by separation of the lipoproteins, revealed substantial carotene binding to very low density lipoprotein (VLDL) and to LDL and limited binding to high density lipoprotein (HDL). Lipid peroxidation of VLDL and LDL were significantly inhibited by beta carotene. The synthetic beta-carotene, however, was twice as effective as the Dunaliella beta-carotene in inhibiting LDL lipid peroxidation (following LDL incubation with copper ions). Cellular degradation of oxidized lipoproteins (mediated via the scavenger receptor) was decreased by 40% and 18%, respectively, when they were prepared by incubation in the presence of synthetic or natural beta-carotene; the control oxidized LDL was prepared in the absence of beta carotene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467014 TI - Analysis of haemoglobin variants using immobilized pH gradients. AB - We present a new method for analysis of haemoglobin variants in immobilized pH gradients. The isoelectric fractionation is performed in polyacrylamide gels with copolymerized pH gradients between pH 7.0 and 8.0. The common haemoglobin variants (HbA, HbF, HbS, HbC, HbE and HbA2) are clearly resolved within this pH range. The high resolving power and reproducibility of immobilized pH gradients combined with extremely short separation times make this fractionation technique superior to all electrokinetic procedures used for haemoglobin analysis. At present, isoelectric focusing in immobilized pH gradients is a complementary tool for haemoglobin analysis when classical electrophoretic techniques do not provide sufficient resolution. We hope that in the future this technique will gain the popularity it deserves. PMID- 8467015 TI - The competitive edge--think like the opposing side to succeed. PMID- 8467016 TI - Laws affect treatment of HIV patients. PMID- 8467017 TI - Surgical treatment of patients with lobar holoprosencephaly: a personal note. AB - The diagnosis of holoprosencephaly usually implies a poor prognosis and is often regarded as a contraindication for surgical correction of associated clefts of the lip or palate. Between 1985 and 1991, 4 patients with lobar holoprosencephaly were evaluated and studied with computed tomography or magnetic resonance imaging. All had cleft palate and 3 had paramedian cleft lip; all 4 exhibited some degree of nasal dysplasia. All patients are presently alive, at a mean age of 26.6 +/- 2.4 months (mean +/- SD). Three of the children showed normal or near normal development, whereas the fourth was severely retarded. Our experience suggests that some children with lobar holoprosencephaly have a highly variable degree of intellectual development and that long-term survival may be expected. PMID- 8467018 TI - Pediatric facial injuries in Tehran: a review of 87 patients. AB - Because of the Iraq/Iran conflict pediatric facial injuries were commonly seen in Iran. A series of 87 facial injuries were isolated from 1,608 patients with different types of facial injuries seen in two university hospitals in Tehran during the previous 6 years (1984-1990). Their ages ranged from 20 months to 13 years. The male-to-female ratio was 16.4:1; the highest incidence was in the lower-third region (63.21%; n = 55), and the highest incidence was in the 8- to 9 year-old age groups. Associated nonfacial injuries, clinical and computed tomographic scan findings for head injuries associated with facial injuries, treatment, and complications are reported. PMID- 8467020 TI - The effect of insulin growth factor-1 on calvarial sutures in a Sprague-Dawley rat. AB - Early investigations attempting to determine the exact pathogenesis of premature closure of the cranial sutures were limited by the untoward sequelae caused by surgical procedures in animal models to simulate the development of craniosynostosis. In an attempt to create a model for evaluating the effects of manipulating the craniofacial sutures without the limitations of associated scarring, we conceived an animal prototype dependent on the effects of insulin growth factor-1 on the anterior frontal suture in a Sprague-Dawley rat model. The experimental group received 2 mg of IGF-1 over a 14-day period via a subcutaneously placed osmotic infusion pump, whereas the age-matched control group received no treatment. We present our preliminary histological results describing the effect of IGF-1 on calvarial sutures. PMID- 8467019 TI - Autogenous reconstruction of the temporomandibular joint. AB - Recently, the temporomandibular joint has been reconstructed with a variety of alloplastic materials; however, functional results are often limited, and long term stability of the reconstruction is questionable. In contrast, costochondral rib grafting with rigid internal fixation and a temporoparietal fascia flap allows complete functional reconstruction of the temporomandibular joint with autogenous tissue. Thirteen joint reconstructions in 11 patients were followed for up to 7 years and stability of the reconstruction was confirmed. The anterior incisal opening improved from a mean of 14 to 31 mm. Normal occlusal relationships were either reestablished or preserved. Joint pain was ameliorated. The preferred reconstruction of the temporomandibular joint is by autogenous tissue for disc and joint replacement. The treatment provides primary therapy in total joint reconstruction where tumor, trauma, or failed prosthetic joint replacement necessitate complete reconstruction. PMID- 8467021 TI - The evolution of the modern human face: Part 1. An anthropological concept. PMID- 8467022 TI - Molded polymethylmethacrylate external retention bolsters for soft-tissue support following medial canthopexy. PMID- 8467023 TI - Osseointegrated implants in cranial bone grafts for mandibular reconstruction. AB - Branemark osseointegrated implants were used in combination with a cranial bone graft that was harvested from the outer table of the skull in a patient with a discontinuity defect of the anterior aspect of the mandible. First, a staged procedure allowed reconstruction of the defect. The second stage was placement of the Branemark osseointegrated implant fixtures, followed by contouring the interior genial area by adding more bone grafts. The initial stabilization was done with an adoption plate that was used to stabilize the mandibular fragments during the healing phase. This plate was subsequently removed when the osseointegrated implants were placed. The patient had a full course of oral rehabilitation and a satisfactory final outcome. PMID- 8467024 TI - Immediate reconstruction of complex cranioorbital fractures in children. AB - Six principles of craniofacial surgery were applied to the treatment of 7 consecutive pediatric patients who sustained complex cranioorbital fractures. These principles are (1) accurate assessment of the deformity, (2) early reconstruction, (3) complete exposure of the involved craniofacial skeleton, (4) accurate anatomical reduction of the fracture fragments, (5) use of rigid internal fixation, and (6) autogenous cranial bone grafting. Patient follow-up ranged from 6 to 52 months; evaluation included serial photographs, three dimensional computed tomographic imaging, and cephalometric analysis. Application of these 6 craniofacial surgical principles provided definitive management in one operation, with optimal anatomical and functional reconstruction, and resulted in no detectable impairment to subsequent craniofacial growth. PMID- 8467025 TI - [Low-dose midazolam reduces the alfentanil demand in elderly but not in young patients during extracorporeal shock wave lithotripsy]. AB - To evaluate whether midazolam has analgesic properties in humans after intravenous injection we studied the influence of a subhypnotic dose of midazolam (50 micrograms/kg) on the cumulative alfentanil consumption in 53 patients during extracorporeal shock wave lithotripsy (ESWL) using a patient-controlled analgesia system (PCAS). In a randomised double blind fashion all patients received either midazolam or an equal volume of saline (placebo) prior to ESWL. Heart rate and arterial blood pressure were measured before and during ESWL. Alfentanil consumption was assessed 20 minutes after injection of midazolam or placebo, respectively. All patients received oxygen via face mask. In patients older than 60 years (median: 70 years, range: 61-88 years) pretreatment with midazolam resulted in a significantly lower cumulative alfentanil consumption (0.41 vs 0.97 mg; p = 0.027) compared with patients younger than 60 years after midazolam pretreatment (0.84 vs 0.71 mg; p = 0.27). Mean arterial pressure also was significantly lower in the former compared with the latter group, while heart rate remained unchanged. In contrast, in patients younger than 60 years (median: 47 years, range: 24-56 years) no significant differences were observed between the midazolam and the placebo group. Thus, low dose intravenous midazolam pretreatment led to a significant decrease of alfentanil consumption in patients beyond 60 years of age. We conclude that subhypnotic doses of midazolam are capable of reducing alfentanil demand in elderly but not in younger patients during ESWL. PMID- 8467026 TI - [N2O-supplemented intravenous anesthesia versus inhalation anesthesia. A comparative study of the sympathoadrenergic reaction and postoperative vigilance]. AB - The aim of the present study was a comparison of the intraoperative sympathoadrenergic response and the postoperative vigilance of a propofol/alfentanil anaesthesia to a conventional isoflurane anaesthesia. 25 patients were admitted to the study undergoing septorhino surgery. Patients with continuous intravenous anaesthesia with propofol/alfentanil combined with nitrous oxide showed better haemodynamic conditions without an increase of blood pressure and catecholamines under laryngoscopy, intubation and surgical stimulation. In contrast to that the patients with isoflurane anesthesia showed a significant increase in haemodynamic parameters and capillary bloodflow. The measured plasma adrenalin levels showed wide intraindividual fluctuation but no significant difference between the groups. The suppression of plasma noradrenaline was more pronounced under intravenous anaesthesia. Recovery was significantly faster and vigilance significantly better in the patients undergoing intravenous anaesthesia. After 30 min patients with i.v. anaesthesia fulfilled all the conditions to be transferred to the regular ward; the other group needed more than one hour. It can be concluded that continuous i.v. anaesthesia with propofol/alfentanil is superior in suppressing the stress response to invasive stimuli and provides faster recovery and better postoperative analgesia. PMID- 8467027 TI - [Prevention of pneumonia by endotracheal micronebulization of tobramycin]. AB - In 69 artificially ventilated patients the clinical, bacteriological and pharmacological effects of endotracheally administered tobramycin were studied in comparison to a control group. In the therapy group, 52% of all specimens were sterile, in the control group only 25%. During the first 4 days these changes were significant (p < 0.05). In the therapy group the endotracheal colonisation with ps. aeruginosa was significantly lower between the 4th and 14th day (p < 0.05). The incidence of secondary pneumonia was reduced from 42% to 17.5% (not significant). Systemic administration of antibiotics, e.g. of aminoglycosides, was significantly more often necessary in the control group. No increasing of growth of fungi in the upper respiratory tract was observed, but these was a non significantly higher incidence mainly of staph. epidermidis. The application of 80 mg tobramycin four times a day as an aerosol was well tolerated by the patients. Under there conditions, tobramycin could not be measured in the serum. No allergic reactions, increased respiratory pressures or bronchoconstrictions were observed. PMID- 8467028 TI - [Hypoxia. Introduction]. PMID- 8467029 TI - [Hypoxia--a significant problem in intensive medicine]. PMID- 8467030 TI - [Diagnosis of the O2 management of the O2 status of the blood]. PMID- 8467031 TI - [Monitoring oxygen transport using pulse oximetry]. PMID- 8467032 TI - [Measurement of oxygen partial pressure in tissue. Clinical results]. PMID- 8467033 TI - [Inhalation anesthetics in patients with coronary heart disease: pro]. PMID- 8467034 TI - [Inhalation anesthetics in patients with coronary heart disease: contra]. PMID- 8467035 TI - [Historical vignette. Compression hyperemia of the head for the prevention of the dreaded poisoning by local anesthetics]. PMID- 8467036 TI - [Septic-toxic heart failure as a result of a heparin-induced thrombocytopenia with "white-clot-syndrome"]. AB - A patient is presented who developed pulmonary artery embolism and thrombocytopenia with various arterial clots several days after an ankle joint osteosynthesis, which finally caused the amputation of the right arm. Unfractionated heparin was applied for the prevention of postoperative thrombosis. Obviously as a consequence of the liberation of toxic metabolites from the gangrenous lower arm, the patient developed septic shock which was exacerbated by a severe pneumonia caused by methicillin-resistant S. aureus bacteria (MRSA). Laboratory investigations showed an antibody (IgG) induced thrombopenia mediated by all low molecular weight and unfractionated heparins. By eliminating heparin and further treatment with a low molecular weight heparinoid (ORG 10,172), platelet count rose sufficiently and thrombotic process ceased completely. Septic shock was successfully treated by fluid replacement, antibiotics and inotropic substances. PMID- 8467037 TI - [Multicultural cooperation in nursing]. PMID- 8467038 TI - ["I do believe that there is something". Discussions with cancer patients]. PMID- 8467039 TI - [Postoperative pain therapy with patient-controlled analgesia (PCA)]. PMID- 8467040 TI - [Pediatric adventure trip into research, knowledge and practice]. PMID- 8467041 TI - [Nutritional problems in long-term nursing home patients]. PMID- 8467042 TI - [Refusal to eat by nursing home patients and what nurses aides and geriatric nurses make of it]. PMID- 8467043 TI - [An ethical analysis of double-bind conflicts of nurses who have to feed severely demented patients]. PMID- 8467044 TI - [Attitude of nurses and their interpretation of the behavior of severely demented patients during feeding in a patient assignment system]. PMID- 8467045 TI - [Nursing education and nursing science--experiences in the United States]. PMID- 8467046 TI - [Stresses on nursing personnel. 2]. PMID- 8467047 TI - [Multiple sorting technique--an example for its application in nursing research]. PMID- 8467048 TI - [The conflict between individual and community care: can we see the woods for the trees?]. PMID- 8467049 TI - [The family and community medicine specialty before homologation with the European Community]. PMID- 8467051 TI - [Auditing the performance of the physician facing patient alcohol consumption]. AB - OBJECTIVE: To assess the Primary Care doctor's performance when faced with his/her patients' alcohol consumption. DESIGN: Retrospective evaluation of data on procedures by means of explicit normative criteria and implicit check-up of those not complying. SETTING: Urban health centre. PATIENTS: A random and institutionally based sample, over a week, of patients of both sexes who came for a general medical consultation (eleven blocks) without prior appointment. RESULTS: 110 clinical histories were evaluated. 60% were not asked about alcohol consumption. In the cases of those who were asked, the amount consumed was specified. Excessive consumption was recorded in the notes as a health risk factor in 87%. A liver profile was requested for 62%. Advice to give up or reduce alcohol consumption was given in all cases. CONCLUSIONS: Poor compliance with the assessment criteria chosen justifies the implementation of the corrective measures proper to quality control methodology. We underline the importance of generalizing the implementation of the Programme of Preventive Activities in Primary Care and the need to improve health professionals' training and motivation on the question. PMID- 8467050 TI - [Self-care measures recorded for acute pathology in primary care]. AB - OBJECTIVE: To quantify and describe the self-treatment existing among users requesting a consultation about an illness which had commenced in the previous 15 days. DESIGN: Observational prospective study. SETTING: Primary care in a semi rural environment. Family Medicine Unit in Valls (Tarragona). PATIENTS AND OTHERS PARTICIPANTS: The study included all those people who attended the Unit, whose illness had begun during the previous 15 days and who were attending with this illness for the first time. The following variables were recorded: gender, age, symptomatology and whether they had taken self-treatment measures (self medication and/or non-pharmacological measures). MEASUREMENTS AND MAIN RESULTS: A total of 375 patients were recorded: 59.5% women and 40.5% men. The most common symptoms were pain (50.1%) and temperature (15.2%). 69.9% of the patients (CI 4.75) had treated themselves: there were no significant differences as regards age and gender. An analysis shows that 18.7% used nonpharmacological measures; 75.9% took some drug; and 5.4% used non-pharmacological measures plus a drug. The most used pharmacological groups were analgesics and antipyretics (40.9%, p < 0.001). CONCLUSIONS: Self-treatment is very common in the Primary Care environment. Professionals and health planners will have to bear this very much in mind, in order both to strengthen its positive implications and correct any negative aspects found. PMID- 8467052 TI - [The time used by the patient when he/she talks without interruptions]. AB - OBJECTIVE: To measure the time used by a patient to explain the reason for his/her visit to the general practitioner, when he/she is permitted to talk freely and without interruption. DESIGN: A descriptive study where only previously known patients, who had a new reason for a consultation, were considered. SETTINGS: Visits to general practitioners' offices in Slovenia and Croatia. PARTICIPANTS: Six general practitioners (two Slovenes and four Croatians) who recorded the time spent on 480 consultations. MEASUREMENTS AND MAIN RESULTS: The period of time measured was that used by the patients, at the beginning of the consultation, to reply to the doctor's question: "What can I do for you today?" Average time used by the patients was 28.6 seconds. There was a link between the older age group and a longer time period. There were no gender differences. CONCLUSIONS: Patients are able to explain calmly and without interruptions the reason for their visit. Interruptions by the doctor are probably unnecessary and do not save time. PMID- 8467053 TI - [The impact on hospital emergency care of the introduction of continuing care into the health centers of Logrono]. AB - OBJECTIVE: To assess the influence in Logrono of the setting-up of "On-going Care Points" (OCP's) on the number of visits to specific Emergency services. DESIGN: Descriptive study. SETTING: Emergency Service of San Millan hospital, Logrono. PATIENTS: All the patients (29,407) seen in the Emergency department of the above hospital during the period under study. RESULTS: After the installation of OCP's, the demand for hospital care fell from a daily average of 172.63 (SD = 21.35) to 164.28 (SD = 17.85). This reduction occurred mainly during the OCPs' opening hours. On non-working days, during these hours, hospital attendance fell from an average of 137.84 (SD = 19.5) to 129.88 (SD = 12.41) (p < 0.05); whereas on working days, it fell from an average of 54.09 (SD = 9.05) to 48.62 (SD = 7.54) (p < 0.001). CONCLUSIONS: We believe that the setting-up of OCP's has been the main reason for the drop in the number of patients seen in the Emergency department. PMID- 8467054 TI - [Compliance with long-term drug treatment: the prescription as a means of health education]. AB - OBJECTIVE: To examine whether the new prescription form, when it is correctly filled in and gives adequate information about the meaning of the treatment instructions, provides long-term patients with a higher level of understanding of their drugs treatment than the old prescription form. DESIGN: Prospective, descriptive study. SETTING: Primary Care level. PATIENTS AND OTHERS PARTICIPANTS: Those users of the Health Area undergoing long-term pharmacological treatments and supervised by the nursing staff using the Health Centre Medication Card. INTERVENTIONS: The 193 users who fulfilled these criteria for inclusion in the study were given three questionnaires. The first contained the old prescription form; the second, the new prescription form, without the spaces for the treatment instructions being filled in; the third, the new form, with the treatment instructions filled in and their meaning explained. MEASUREMENTS AND MAIN RESULTS: Users were faced with the old prescription form and the new one correctly filled in plus explanation. Comparison between the two showed that out of 38 cases of error with the old form, 14 (36.84%) increased their understanding of the treatment. This was a statistically significant improvement: [Tc] < [Te] with an average of (-3.77), with a typical deviation of 1.16 and p < 0.05. CONCLUSIONS: The prescription form can be a good way of improving the efficacy of staff intervention. PMID- 8467055 TI - [The usefulness of the Munich Alcoholism Test (MALT) in the diagnosis of alcoholism]. PMID- 8467056 TI - [The diagnosis and treatment of the most frequent menstrual changes in primary care (and II)]. PMID- 8467057 TI - [The evaluation of an influenza vaccination campaign in a health sector]. PMID- 8467058 TI - [A case of AIDS in primary care]. PMID- 8467059 TI - [Pregnancy due to the failure of a hormonal contraceptive method]. PMID- 8467060 TI - [Risk factors and the cult of the body]. PMID- 8467061 TI - [PPD and chemoprophylaxis in diabetes]. PMID- 8467062 TI - The influence of hydration on the conformation of lysozyme studied by solid-state 13C-NMR spectroscopy. AB - 13C proton decoupled cross-polarization magic-angle spinning nmr spectra of lysozyme are reported as a function of hydration. Increases in hydration level enhance the resolution of the spectra, particularly in the aliphatic region, but has no significant effect on either the rotating frame proton spin-lattice relaxation time or the cross-relaxation time. The enhancement in spectral resolution with hydration is attributed to a decrease in the distribution of isotropic chemical shifts, which reflects a decrease in the distribution of conformational states sampled by the protein. Changes in the distribution of isotropic chemical shifts occur after the addition of water to the charged groups as coverage of the polar side chains and peptide groups takes place. The onset of this behavior occurs at a hydration level of about 0.1-0.2 g water/g protein and is largely complete at about 0.3 g water/g protein, the same hydration range where changes in the heat capacity are observed. That hydrogen exchange of buried protons can occur at hydration levels significantly lower than those at which changes in the distribution of conformational states are first observed suggests that some motions that mediate exchange are already present in the dry protein. The preservation of efficient dipolar coupling indicates that the conformational rearrangements that do occur on hydration are small and do not involve any significant overall expansion of free volume or weakening of interactions that would increase the reorientational freedom of protein groups. PMID- 8467063 TI - Effects of molecular association on structure and dynamics of a collagenous peptide. AB - Peptide GVKGDKGNPGWPGAPY from the triple-helix domain of type IV collagen aggregates in solution at a critical aggregation concentration of 18 mM. This molecular self-association process is investigated by 1H- and 13C-nmr spectroscopy. As a function of increasing peptide concentration, selective 1H resonances are cooperatively chemically shifted by up to 0.04 ppm to apparently saturable values at high concentration. Pulsed field gradient nmr was used to derive translation diffusion constants that, as the peptide concentration is increased, also cooperatively and monotonically decrease to an apparent limiting value. An average number of 6 monomer units per aggregate have been estimated from diffusion constant and 13C relaxation data. Comparative 1H nuclear Overhauser effect spectroscopy (NOESY) spectra accumulated at high and low peptide concentrations suggest that average internuclear distances are decreased as a result of peptide association. 13C-nmr multiple spin-lattice relaxation and 13C-[1H] NOE effects on 13C-enriched glycine methylene positions in the peptide demonstrate that overall molecular tumbling and backbone internal motions are attenuated in the aggregate state. Lowering the solution pD from pD 6 to pD 2 disrupts the aggregate state, suggesting a role for electrostatic interactions in the association process. Based on thermodynamic considerations, hydrophobic interactions also probably act to stabilize the aggregate state. These data are discussed in terms of an nmr/NOE constrained computer-modeled structure of the peptide. PMID- 8467064 TI - Dynamic light scattering of aqueous solutions of linear aggregates induced by thermal denaturation of ovalbumin. AB - Dynamic light scattering measurements were performed on dilute aqueous solutions of native ovalbumin (OA) and on those of linear OA aggregates induced by thermal denaturation at low ionic strength and neutral pH. The weight-average molecular weight MW of four aggregates tested ranged from 1,700,000 to 5,500,000. The translational diffusion coefficient D0 of native OA at infinite dilution was estimated as 8.70 x 10(-7) cm2/s, which gave 56.0 A as the diameter of the rigid spherical particle. The intensity autocorrelation function of linear OA polymers was analyzed with the cumulant method to obtain the first cumulant gamma e. The dependence of gamma e on the scattering vector q at very low polymer concentration was found intermediate between those of a flexible chain and a rigid rod. The translational diffusion coefficient Dtr [identical to (gamma e/q2)q-->0] was in proportion to M-0.55W, and the magnitude was in good agreement with a value calculated from the wormlike cylinder model with values of three parameters determined in an earlier study, ML = 1600 A-1, d = 120 A, and Q = 230 A, where ML, d, and Q are the molecular weight per unit length, diameter, and persistence length, respectively. Based on these results, a new model, to be called as the dimer model, was proposed to interpret the formation mechanism of linear OA polymers induced by thermal denaturation. PMID- 8467065 TI - Physicochemical properties of (1-->6)-branched (1-->3)-beta-D-glucans. 1. Physical dimensions estimated from hydrodynamic and electron microscopic data. AB - The physical dimensions of several (1-->6) branched (1-->3)-beta-D-glucan samples obtained from different organisms and their derivatives have been studied by electron microscopy, light scattering measurements, viscometry, and gel permeation chromatography. The electron micrographs indicate that in most samples these biopolymers are adequately described as linear worm-like coils. A sample reconstituted from alkaline media appeared as a blend of the linear, circular, and aggregated polymer morphologies. The average mass per unit length, ML = Mw/Lw for the macroscopically linear samples, was estimated to be 2100 +/- 200 g mol-1 nm-1. The parameter ML was determined from the contour lengths obtained by electron microscopy and the molecular weight by light scattering measurements. The observed ML was consistent with the triple-helical structure reported from x ray diffraction studies and observed degree of side-chain substitution. From the molecular snapshots shown in the electron micrographs, the persistence lengths of these beta-D-glucans were determined to be 140 +/- 30 nm. The experimentally determined intrinsic viscosities were consistent with these estimates of ML and persistence length. Comparison of the molecular weight distributions obtained from gel permeation chromatography and those deduced from the electron micrographs indicates that number and weight average contour lengths are more reliable than z and z + 1 averages. PMID- 8467066 TI - Reversible effects of medium dielectric constant on structural transformation of beta-lactoglobulin and its retinol binding. AB - The secondary structure transformation of beta-lactoglobulin from a predominantly beta-structure into a predominantly alpha-helical one, under the influence of solvent polarity changes is reversible. Independent of the alcohol used- methanol, ethanol, or 2-propanol--the midpoints of the observed structural transformation occur around dielectric constant epsilon approximately 60. The structural change destroying the hydrophobic core formed by the beta-barrel structure leads, at room temperature, to the dissociation of the retinol/beta lactoglobulin complex in the neighborhood of dielectric constant epsilon approximately 50. However, when the dielectric constant of the medium is raised back to epsilon approximately 70 by the decrease of the temperature, both the refolding of BLG into a beta-structure and the reassociation of the retinol/beta lactoglobulin complex are observed. The esterification of beta-lactoglobulin carboxyl groups has two effects: on the one hand it accelerates the beta strand<==>alpha-helix transition induced by alcohols. On the other hand, the esterification of beta-lactoglobulin strengthens its interaction with retinol as it may be deduced from the smaller apparent dissociation constant of retinol/methylated beta-lactoglobulin complex. The binding of retinol to modified or unmodified beta-lactoglobulin has no influence (stabilizing or destabilizing) on the folding changes induced by alcohol. PMID- 8467067 TI - Design of peptides: crystal and molecular structure of a 3(10)-helical peptide N Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val-OCH3. AB - Highly specific peptide structures can be designed by inserting dehydro residues into peptide sequences. The peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro Phe-L-Val- OCH3, synthesized by conventional procedures, crystallizes from methanol-water mixtures at 4 degrees C in the tetragonal space group P4(3) with cell parameters a = b = 13.829 +/- 0.003 A, c = 27.587 +/- 0.008 A, V = 5275.5 +/ 0.2 A3, Z = 4, dm = 1.152 +/- 0.005 g cm-3, dcal = 1.150 +/- 0.005 g cm-3. The overall residual factor R = 0.084 for 2342 reflections, with 2 theta max = 140 degrees using CuK alpha radiation. The backbone torsion angles are theta 1 = 171(1) degrees, omega 0 = 168(1) degrees, phi 1 = 77(2) degrees, psi 1 = 41(2) degrees, omega 1 = 169(1) degrees, phi 2 = -46(2) degrees, psi 2 = -24(2) degrees, omega 2 = 179(1) degrees, phi 3 = -63(2) degrees, psi 3 = 19(2) degrees, omega 3 = 171(1) degrees, phi 4 = -67(2) degrees, psi 4 = -8(1) degrees, omega 4 = 169(1) degrees, phi 5 = -61(1) degrees, psi 5 = -26(1) degrees, omega 5 = 177(1) degrees, phi 6 = -122(1) degrees, psi 6T = 26(2) degrees. The peptide adopts a 3(10)-helical conformation with three intramolecular hydrogen bonds (i + 3-->i) involving carbonyl oxygen atoms of Phe1, dehydro-Phe2, Val3, and the NH groups of Phe4, dehydro-Phe5, and Val6 with distances of 3.01(1), 2.82(1), and 3.09(2) A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467068 TI - beta-Alanine containing peptides: gamma-turns in cyclotetrapeptides. AB - In the present paper we describe the synthesis, purification, single-crystal x ray analysis, solution conformational characterization, and conformational energy calculations of the cyclic tetrapeptide cyclo-(beta-Ala-L-Pro-beta-Ala-L-Val). The peptide was synthesized by classical solution methods and the cyclization of the free tetrapeptide was accomplished in good yields in diluted methylene chloride solution using N,N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P2(1) from ethanol with two independent molecules in the unit cell. All peptide bonds are trans. The nmr molecular conformation in the acetonitrile solution as well as that derived from the molecular dynamic simulation in vacuo is quite different from those observed in the solid state and is very similar to that previously observed for the parent compound cyclo- (beta Ala-L-Pro-beta-Ala-L-Pro). PMID- 8467069 TI - The effect of intrinsic curvature on supercoiling: predictions of elasticity theory. AB - Elasticity theory of naturally curved rods is employed to study the effects of intrinsic curvature on the properties of the equilibrium conformations of supercoiled DNA. The results stand in sharp contrast to those obtained when the molecule is viewed as being straight in its relaxed form. Starting from very fundamental principles of the theory, we show that the torsion of an open segment with a curved duplex axis can vary when the temperature, and along with it, the intrinsic twist is changed. Conversely, an imposed helicity, such as might be associated with binding to a histone, can change the intrinsic twist. It is also shown that another consequence of the presence of naturally curved sequences is that the twist density will, in general, vary with position along the chain in all equilibrium states. Then portions of the molecule will be more or less susceptible to interaction with other agents sensitive to such a variation. Finally, some closed equilibrium global structures uniquely associated with intrinsic curvature are discussed. PMID- 8467070 TI - Synthesis and conformational analysis of N-glycopeptides. II. CD, molecular dynamics, and NMR spectroscopic studies on linear N-glycopeptides. AB - The comprehensive structural analysis reported herein of eight N-glycopeptides, in three different solvents, is based on quantitative CD experiments, homonuclear nuclear Overhauser effect measurements, and molecular dynamics (MD) calculations. Although several orientations of the two amide planes attached to the carbohydrate pyranose ring are possible, according to NOE, CD data, and MD simulations, of all of the glycopeptide models, regardless of the type of the carrier peptide, only one dominant conformer population was found. This conformer is characterized by a nearly trans orientation of the CH and NH hydrogens of both acetamido groups. This finding is in perfect agreement with x-ray crystallographic data on the solid state conformation of the 1-N-acetyl- and 1-N (beta-aspartyl)-2-acetamido-2-deoxy-beta-D-glucopyranosyla min e. The precise identification of this dominant conformer of N-glycopeptides in solution was the major question addressed herein by the structural analyses. A "CD additivity" experiment was carried out using an equimolar solution of Boc-Pro-Asp-NHCH3 and 1 N-acetyl-3,4,6- tri-O-acetyl-2-acetamido-2-deoxy-beta-D-glucopyranosylamine at ambient temperature in acetonitrile. The CD spectrum obtained from the equimolar solution of the above two molecules (the "spectroscopic sum") was identical with the CD curve obtained from the algebraic summation of the individually recorded CD spectra of the peptide and the carbohydrate moiety ("mathematical sum"). The global picture of the CD spectral analyses of the eight parent peptides with the eight N-glycopeptides revealed that in trifluoroethanol and acetonitrile, the side-chain modification of the Asn models (natural N-glycopeptide analogues) by N glycosylation has a significant effect on the conformation of the carrier peptide, resulting in a decrease in the original type I beta-turn content. Simultaneously, the type II beta-turn conformational percentage increased to approximately 20%. Such a conformational ratio change seems to be larger than the expected errors arising from the CD analyses, and agrees with the results of MD calculations. N-glycosylation of Asn residues causes perturbations, not only through the covalent bond, but also through specific hydrogen bonds between the backbone and side chain atoms. CD spectroscopy, augmented by efficient CD curve deconvolution techniques, has proved to be a useful tool for studying multicomponent conformer mixtures of small linear peptides in solution and changes of conformational equilibria caused by N-glycosylation. PMID- 8467071 TI - Cyanogen as a selective probe for carbonic anhydrase hydrolase activity. AB - The salt bridge probe cyanogen (ethanedinitrile, C2N2; N identical to C-C identical to N) inhibits the bovine carbonic anhydrase (EC 4.2.1.1.) hydrolase activity toward various types of esters without significant effect on its hydrolyase activity. Two sets of pyridine derivatives that were isosteric substrates for the two activities were differentially affected. Acetazolamide and salamide are reversible inhibitors of the enzyme; only salamide affords protection of the hydrolase activity against the action of C2N2. Since each is known to bind in different positions within the active site, the selective effect of salamide may arise from its position covering one CO2 site as well as a site important for hydrolase activity. The C2N2 concentration dependence of the time course of hydrolase inhibition is consistent with the existence of a high C2N2 affinity site with slow covalent change and a second site with lower C2N2 affinity, but higher rate of covalent modification of the enzyme. PMID- 8467072 TI - NMR and computer-aided studies of the three interchanging stereoisomers of the cyclic hexapeptide cyclo[-Pro1-Gly2-Glu3(OBzl)-Pro4-Phe5-Leu6-]: unexpected observation of a cis isomer of a secondary amide peptide bond in the presence of two trans proline peptide bonds. AB - The cyclic hexapeptide cyclo[-Pro1-Gly2-Glu3(OBzl)-Pro4-Phe5-Leu6-] (1; OBzl: benzyl ester) was modeled and synthesized to be used as a chiral site for the separation of enantiomers. Total correlation spectroscopy and nuclear Overhauser effect spectroscopy spectra of the peptide in CDCl3 showed the presence of three stereoisomers. The two dominant stereoisomers 1a and 1b exchanged chemically with each other, while the minor stereoisomer 1c exchanged exclusively with the stereoisomer 1b. Stereoisomer 1a had two cis proline peptide bonds while stereoisomer 1b had all-trans peptide bonds. The stereoisomer 1c had, for nonstrained peptides, an unusual cis phenylalanine peptide bond while both proline peptide bonds were trans. PMID- 8467073 TI - Isolation and characterization of a cDNA encoding NADP(+)-specific isocitrate dehydrogenase from soybean (Glycine max). AB - A cDNA that encodes an NADP-specific isocitrate dehydrogenase (IDH) was cloned from a soybean nodule cDNA library by complementation of an Escherichia coli mutant that lacked IDH. DNA sequence analysis showed that the 1583 bp soybean cDNA could encode a protein that shares 63.9% amino acid sequence identity with the Saccharomyces cerevisiae NADP-IDH and long sequences of identity to an IDH from pig. Southern blot analysis suggests that this gene corresponds to a gene family made up of no more than two loci. The IDH cDNA hybridized to a 1.7 kb soybean mRNA and the relative amount of this transcript in soybean leaves, nodules and roots was 1:3.4:7.7. In alfalfa, a 1.7 kb mRNA was also found but the ratios for the corresponding tissues were 1:7.4:7.7. IDH activity was detected in the complemented E. coli strain and the electrophoretic mobility of this activity in nondenaturing polyacrylamide gels was identical to that of an IDH in extracts from soybean cotyledons or nodule cytosol. NADP-IDH specific activity in the E. coli host strain varied with growth phase; the highest rates (ca. 180 nmol/min per mg protein) were observed in late-stationary-phase cells. The enzyme had a broad pH optimum of 8.0 to 9.5 and had an absolute metal cofactor requirement, preferring Mn2+ below pH 8.0 and Mg2+ above pH 8.0. The Km for isocitrate and NADP was 21 microM and 11 microM respectively with Mn2+ as cofactor and 13 microM and 12 microM with Mg2+ as cofactor. PMID- 8467074 TI - The Rubisco activase (rca) gene is located downstream from rbcS in Anabaena sp. strain CA and is detected in other Anabaena/Nostoc strains. AB - A gene encoding ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase (rca) was found downstream from the rbcLrbcS operon in the heterocystous cyanobacterium Anabaena sp. strain CA. Two unknown open reading frames were shown to be located between rbcS and rca in strain CA and all the genes, rbcLrbcS, ORF1, ORF2, and rca were in the same transcriptional orientation. The deduced amino acid sequence of the Anabaena Rubisco activase showed both similarities and differences to the plant enzyme with considerable differences at the carboxy and amino termini. Proposed ATP-binding sites were conserved in the cyanobacterial protein. Recombinant cyanobacterial Rubisco activase, however, reacted with antisera to spinach Rubisco activase. Hybridization studies, using the Anabaena sp. strain CA rca gene as a heterologous probe, detected homologous sequences in heterocystous Anabaena/Nostoc strains but not in unicellular or nonheterocystous filamentous cyanobacteria, suggestive of a close evolutionary relationship of chloroplasts and heterocystous cyanobacteria. PMID- 8467075 TI - Sequence analysis of 22 kDa-like alpha-coixin genes and their comparison with homologous zein and kafirin genes reveals highly conserved protein structure and regulatory elements. AB - Several genomic and cDNA clones encoding the 22 kDa-like alpha-coixin, the alpha prolamin of Coix seeds, were isolated and sequenced. Three contiguous 22 kDa-like alpha-coixin genes designated alpha-3A, alpha-3B and alpha-3C were found in the 15 kb alpha-3 genomic clone. The alpha-3A and alpha-3C genes presented in-frame stop codons at position +652. The two genes with truncated ORFs are flanking the alpha-3B gene, suggesting that the three alpha-coixin genes may have arisen by tandem duplication and that the stop codon was introduced before the duplication. Comparison of the deduced amino acid sequences of alpha-coixin clones with the published sequences of 22 kDa alpha-zein and 22 kDa-like alpha-kafirin revealed a highly conserved protein structure. The protein consists of an N-terminus, containing the signal peptide, followed by ten highly conserved tandem repeats of 15-20 amino acids flanked by polyglutamines, and a short C-terminus. The difference between the 22 kDa-like alpha-prolamins and the 19 kDa alpha-zein lies in the fact that the 19 kDa protein is exactly one repeat motif shorter than the 22 kDa proteins. Several putative regulatory sequences common to the zein and kafirin genes were identified within both the 5' and 3' flanking regions of alpha 3B. Nucleotide sequences that match the consensus TATA, CATC and the ca. -300 prolamin box are present at conserved positions in alpha-3B relative to zein and kafirin genes. Two putative Opaque-2 boxes are present in alpha-3B that occupies approximately the same positions as those identified for the 22 kDa alpha-zein and alpha-kafirin genes. Southern hybridization, using a fragment of a maize Opaque-2 cDNA clone as a probe, confirmed the presence of Opaque-2 homologous sequences in the Coix and sorghum genomes. The overall results suggest that the structural and regulatory genes involved in the expression of the 22 kDa-like alpha-prolamin genes of Coix, sorghum and maize, originated from a common ancestor, and that variations were introduced in the structural and regulatory sequences after species separation. PMID- 8467076 TI - Secondary structure and phylogeny of the chloroplast 23S rRNA gene from the brown alga Pylaiella littoralis. AB - The entire nucleotide sequence of a 23S rRNA gene from the brown alga Pylaiella littoralis (L.) Kjellm has been determined. The predicted length of the 23S rRNA is 2948 nucleotides, including the 4.5S rRNA-like region at the 3' end of the molecule. The putative transcript has been folded into a secondary structure by comparison to existing structure models, and the predicted helical regions were inspected by identifying compensatory downstream base changes. The 23S rRNA secondary structure presented here has features that are unique to P. littoralis (no other chromophyte or red algal 23S rRNA sequences are yet available), but has none of the features specific to the chloroplast rRNAs of green plants and green algae. The Pylaiella sequence was aligned with analogous plastidial and eubacterial gene sequences, and the alignment was used to construct a phylogenetic tree. The plastidial sequences formed a coherent cluster closely associated with the 23S rRNA of the cyanobacterium Anacystis nidulans. Within the plastid group, the P. littoralis sequence was most closely related to that of Euglena gracilis confirming earlier analyses based upon 16S rRNA sequences. PMID- 8467077 TI - Organization of the genes encoding chalcone synthase in Pisum sativum. AB - To analyze the regulation of defense-related genes by signal molecules produced by phytopathogens, we isolated genes that encode chalcone synthase (CHS) in Pisum sativum. We have obtained seven independent genomic clones that contain at least seven classes of CHS genes, identified by the hybridization analysis to CHS cDNA and by the restriction mapping analysis. Two of the genomic clones (clone 5 and 6) each contain two CHS genes in a tandem repeat. The nucleotide sequence analysis of CHS genomic clone 5 revealed that PsCHS1 and PsCHS2 were corresponding genes of the CHS cDNA clones, pCC6 and pCC2, respectively, as reported earlier. Both genes are interrupted by a single intron of 88 nucleotides with identical sequences, although exonic sequences and 5'-flanking sequences are divergent. Nucleotide sequences of the introns in five other classes of CHS genes showed that three classes had an intron of 87 nt with a striking homology to each other, but that the intron of the other two classes of CHS genes showed heterogeneity both in size and nucleotide sequence. 5'-upstream regions of PsCHS1 and PsCHS2 did not show sequence homology except the 31 bp identical sequence that contains the CCTACC motif resembling the box-1 sequence. Both PsCHS1 and PsCHS2 genes are shown to be induced by fungal elicitor by a primer extension analysis and a transient transformation analysis using pea protoplasts prepared from suspension cultured-cells. PMID- 8467078 TI - Transient gene expression of foreign genes in preheated protoplasts: stimulation of expression of transfected genes lacking heat shock elements. AB - Transfection of preheated petunia protoplasts with several biologically active DNA constructs resulted in a significantly higher gene expression than that observed in transfected unheated protoplasts. It was observed with supercoiled, linearized and single-stranded DNA structures that stimulation of transient gene expression in preheated protoplasts was neither dependent on the reporter gene nor on the regulatory elements used. Heat treatment at 42 degrees C also increased expression in protoplasts transfected with a plasmid bearing the tobacco mosaic virus (TMV) translational enhancer, omega. Northern blot analysis revealed that heat treatment of protoplasts before the transfection event greatly increased the amount of the newly synthesized transcripts. Preheating of protoplasts did not affect the transfection efficiency, namely the number of transfected cells in the population, nor the amount of DNA in transfected nuclei, as was inferred from histochemical staining and Southern blot analysis, respectively. The possible mechanism by which heat treatment stimulates transient gene expression of genes lacking obvious heat shock elements is offered. The relevance of the present findings to transient gene expression in plants in general and to viral gene expression in particular is discussed. PMID- 8467079 TI - Isolation and characterization of the genes encoding allophycocyanin subunits and two linker proteins from Synechocystis 6714. AB - Genes encoding the phycobilisome core subunits allophycocyanin alpha and beta and a small core linker protein in Synechocystis sp. strain PCC 6714 were cloned and sequenced. These genes form an operon, apcABC, with a single transcription start site and two possible termination sites, one following apcB and the other following apcC. The promoter region, like those of the apcABC operons of other cyanobacteria, does not resemble the consensus promoter sequences of Escherichia coli. However, the apcABC promoters identified in four strains of cyanobacteria have conserved sequences centered at -50 and -10 with respect to the start of transcription. The apcE gene, encoding the protein that links the phycobilisome core to the thylakoid membrane, was also cloned from Synechocystis 6714 and sequenced. It is unlinked to the apcABC operon. As in other Synechocystis strains, the LCM polypeptide encoded by the apcE gene contains three repeats of the basic phycobiliprotein linker domain. The apcE gene promoter sequence bears little resemblance to either the E. coli consensus or the apcABC promoter region, but it is similar to the corresponding regions of other cyanobacterial apcE genes. In these cases, there are conserved sequences centered at -40 and -10 with respect to the transcription start site. These conserved promoter elements from the apcABC and apcE genes were also identified in the corresponding 5'-flanking regions of eleven transcript starts for cpc genes encoding phycocyanin subunits in cyanobacteria and algal chloroplasts. These results suggest that a factor yet to be described participates in transcription of phycobiliprotein genes. PMID- 8467081 TI - Molecular basis for extensin size heterogeneity in two maize varieties. AB - This study concerned the molecular basis for the protein size heterogeneity of extensin from two maize (Zea mays L.) varieties. We studied the physical properties of extensin, a hydroxyproline-rich glycoprotein (HRGP), from the silk and pericarp of Golden X Bantam (GXB) sweet corn and Japanese Hulless (JHL) popcorn. Extensin from GXB has a molecular mass of 66 kDa whereas extensins from JHL have molecular masses of 76 and 66 kDa. Treatment with anhydrous hydrogen fluoride to deglycosylate proteins reduced the size of all extensins by 5 kDa. Probing with a 500 bp fragment from a genomic clone of maize extensin identified two transcripts (1.9 and 1.5 kb) on northern blots. JHL contained both transcripts and GXB contained only the 1.5 kb transcript. The probe also hybridized to two larger transcripts (6.2 and 4.5 kb) that were found in both varieties. We immunoprecipitated two proteins (66 and 56 kDa) from translated RNA isolated from JHL and one protein (56 kDa) from GXB. These results demonstrate that these extensins differ in the size of their peptide moiety and not in their extent of glycosylation. PMID- 8467080 TI - Use of bar as a selectable marker gene and for the production of herbicide resistant rice plants from protoplasts. AB - We have used the bar gene in combination with the herbicide Basta to select transformed rice (Oryza sativa L. cv. Radon) protoplasts for the production of herbicide-resistant rice plants. Protoplasts, obtained from regenerable suspension cultures established from immature embryo callus, were transformed using PEG-mediated DNA uptake. Transformed calli could be selected 2-4 weeks after placing the protoplast-derived calli on medium containing the selective agent, phosphinothricin (PPT), the active component of Basta. Calli resistant to PPT were capable of regenerating plants. Phosphinothricin acetyltransferase (PAT) assays confirmed the expression of the bar gene in plants obtained from PPT resistant calli. The only exceptions were two plants obtained from the same callus that had multiple copies of the bar gene integrated into their genomes. The transgenic status of the plants was verified by Southern blot analysis. In our system, where the transformation was done via the protoplast method, there were very few escapes. The efficiency of co-transformation with a reporter gene gusA, was 30%. The T0 plants of Radon were self-fertile. Both the bar and gusA genes were transmitted to progeny as confirmed by Southern analysis. Both genes were expressed in T1 and T2 progenies. Enzyme analyses on T1 progeny plants also showed a gene dose response reflecting their homozygous and heterozygous status. The leaves of T0 plants and that of the progeny having the bar gene were resistant to application of Basta. Thus, the bar gene has proven to be a useful selectable and screenable marker for the transformation of rice plants and for the production of herbicide-resistant plants. PMID- 8467082 TI - Unusual sequence of group 3 LEA (II) mRNA inducible by dehydration stress in wheat. AB - A cDNA clone, pMA1949, detects two mRNA species in wheat seedling tissue that are late embryogenesis-abundant (LEA) and dehydration stress-inducible. Sequence analysis of the pMA1949 clone shows it to be a 991 bp partial cDNA encoding a polypeptide of 317 amino acids with homology to two group 3 LEA proteins, carrot (DC8) and a soybean protein encoded by pGmPM2 cDNA. Molecular analysis of the deduced protein reveals a 33 kDa acidic and extremely hydrophilic protein with potential amphiphilic alpha-helical regions. In addition, the protein contains eleven similar, contiguous repeats of 11 amino acids, which are separated by 118 amino acids from two additional and unique repeats of 36 residues each at the carboxyl end of the protein. Comparisons of sequences of reported group 3 LEA proteins revealed that there are two types, separable by sequence similarity of the 11 amino acid repeating motifs and by the presence or absence of a certain amino acid stretch at the carboxyl terminus. Based on results from these comparisons, we propose a second type of group 3 LEA proteins, called group 3 LEA (II). PMID- 8467083 TI - Structure of a cyanobacterial gene encoding the 50S ribosomal protein L9. AB - The rplI gene encoding the ribosomal protein L9 was found 4 kbp downstream from the desA gene, but on the opposite strand, in the genome of the cyanobacterium Synechocystis PCC6803. The deduced amino acid sequence is homologous to the sequences of the L9 proteins from Escherichia coli and chloroplasts of Arabidopsis and pea. The gene is present as a single copy in the chromosome and is transcribed as a mRNA of 0.64 kb. An open reading frame of unknown function (ORF291) was found in the upstream region of the rplI gene. PMID- 8467084 TI - A large DNA repeat of the dispersion pattern common to wheat and rye genomes. AB - A Hind III-generated fragment of wheat embryo nuclear DNA has been cloned and sequenced. The cloned fragment corresponds to a 1241 bp long, moderately repeated (60,000 copies/genome) segment of the genomic DNA. The repeat is AT-rich (67%), contains an open reading frame for 151 amino acids and several nucleotide blocks resembling the consensus domain of autonomously replicating sequences. Southern blot hybridization analyses indicate that the repeat is scattered through the wheat genome. A sequence homologous to this repeat occurs also in rye embryo nuclear DNA where it shows the same dispersion pattern as that observed for the wheat repeat. PMID- 8467085 TI - Molecular characterization of salt-stress-associated protein in citrus: protein and cDNA sequence homology to mammalian glutathione peroxidases. AB - A gene encoding for a citrus salt-stress-associated protein (Cit-SAP) was cloned from Citrus sinensis salt-treated cell suspension. The gene, designated csa, was isolated from a cDNA expression library. The partial amino acid sequence of the protein, as well as that deduced from the nucleotide sequence of csa, revealed a considerable homology to mammalian glutathione peroxidase (GP), and to clone 6P229 from tobacco protoplasts. The increased expression of Cit-SAP in NaCl treated cultured citrus cells and in citrus plants irrigated with saline water, and its similarity to GP, raise the possibility that one of the effects of salt stress in plants may be the increase of the level of free radicals. PMID- 8467086 TI - Tissue-specific expression of a plant turgor-responsive gene with amino acid sequence homology to transport-facilitating proteins. AB - We report the isolation of a turgor-responsive gene of pea, trg-31, whose transcription induced within 30 min after the loss of leaf turgor. Structure of the coding region and 1.4 kb of 5' untranslated region was determined by DNA sequencing. A 3 kb promoter fragment from trg-31 was fused to a beta glucuronidase (GUS) reporter gene in pBI101, tobacco leaf disks and mature plants analyzed for turgor-responsive induction of GUS mRNA. Significant amino acid sequence homology exists between trg-31 and putative transport proteins of bovine, Phaseolus, soybean and Escherichia coli membranes. PMID- 8467087 TI - Semi-constitutive expression of an Arabidopsis thaliana alpha-tubulin gene. AB - In Arabidopsis tissues, the pool of tubulin protein is provided by the expression of multiple alpha-tubulin and beta-tubulin genes. Previous evidence suggested that the TUA2 alpha-tubulin gene was expressed in all organs of mature plants. We now report a more detailed analysis of TUA2 expression during plant development. Chimeric genes containing TUA2 5'-flanking DNA fused to the beta-glucuronidase (GUS) coding region were used to create transgenic Arabidopsis plants. Second generation progeny of regenerated plants were analyzed by histochemical assay to localize GUS expression. GUS activity was seen throughout plant development and in nearly all tissues. The blue product of GUS activity accumulated to the highest levels in tissues with actively dividing and elongating cells. GUS activity was not detected in a few plant tissues, suggesting that, though widely expressed, the TUA2 promoter is not constitutively active. PMID- 8467088 TI - Post-transcriptional transfer of gamma-thio affinity label to RNA in isolated parsley nuclei. AB - As an alternative to soluble plant transcription systems, we examined the reinitiation capacity of isolated parsley nuclei. Nuclear chalcone synthase in vitro transcripts were affinity-labelled with gamma-thio-ATP, gamma-thio-GTP or beta-thio-ATP, and purified by chromatography on a mercury Sepharose affinity column. Primer extension and subsequent PCR amplification of these in vitro transcripts revealed gamma-thio-ATP-dependent, but no beta-thio-ATP-dependent, signals, although affinity labelling of overall in vitro transcripts still occurred with beta-thio-ATP. We conclude that the described plant nuclei reinitiated transcription non-specifically and that post-transcriptional transfer of the gamma-thio affinity label severely interfered with the detection of reinitiated transcripts. PMID- 8467089 TI - Sequence of a sugarcane ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit gene. PMID- 8467090 TI - Interaction of the T cell receptor with bacterial superantigens. AB - Bacterial toxin superantigens bind to MHC class II molecules and activate a large proportion of T cells through a direct interaction with the T cell receptor (TCR). The toxin: TCR interaction involves specific recognition between the beta chain variable region and the toxin. Although a complete alpha beta T cell receptor is required for activation of T cells, studies using purified soluble T cell receptor beta-chain have shown that it alone is sufficient for binding the toxin: class II complex. The regions of V beta and enterotoxin involved in the recognition have been determined. PMID- 8467091 TI - Interactions between staphylococcal superantigens and MHC class II molecules. AB - Superantigen binding to MHC class II molecules is a prerequisite for T cell stimulation. While the presentation of superantigens is not MHC restricted, allelic and isotypic variations in the ability of class II molecules to interact and present these superantigens exist. SEs bind to MHC class II molecules outside of the peptide binding groove, differences in binding affinities of the toxins for class II alleles and isotypes have been shown. In addition, a direct interaction between T cell receptor and MHC class II molecules could be responsible for these differences. In this review we provide a molecular analysis of the interactions of SEs with class II molecules. PMID- 8467092 TI - Superantigens of microbial origin. AB - Food poisoning associated staphylococcal enterotoxins and other bacterial products of diverse origin are now the focus of immunological research. These substances have special properties which determine their designation as superantigens. They influence T cell functions by controlling their repertoire, their cytokines production and their modulation of the immune response. As a consequence, superantigens might be at the origin of bacterial and autoimmune diseases. In this review we describe mainly the staphylococcal enterotoxins as representative members of the superantigen family. PMID- 8467093 TI - The CD8 T cell response to staphylococcal enterotoxins. AB - Staphylococcal enterotoxins (SE) are superantigens that bind to MHC class II molecules and activate T lymphocytes via the T cell receptor (TCR) V beta domain. By analogy with T cell responses to conventional peptide antigens, it might be predicted that CD4 (MHC class II restricted) cells would respond better to SE than CD8 (MHC class I restricted) cells. Here we summarize evidence that in fact CD8 cells respond as well as CD4 cells to SE both in vitro and in vivo. These findings emphasize the unique character of TCR-superantigen interactions. PMID- 8467094 TI - Gamma delta T cell reactivity towards bacterial superantigens. AB - Human TCR gamma delta positive T cells can proliferate in response to stimulation with staphylococcal enterotoxins (SEs) or mediate lysis of SE pulsed target cells. In the small number of studies reported, the proliferative response of gamma delta T cells was limited to V gamma 9 negative cells and, in vitro, such responses do not require the presence of MHC class II molecules for antigen presentation. Proliferative responses have been found after stimulation with SEA, SEB and TSST. The cytolytic activity of gamma delta T cells can be mediated by two different mechanisms: either gamma delta T cells specifically interact with SEA pulsed target cells--this is most likely TCR mediated recognition--or gamma delta T cells mediate antibody dependent cellular cytotoxicity (ADCC). This latter reactivity depends on Fc-receptor expression by the gamma delta T cell clones and the presence of SE specific antibodies during the assay. So far cytotoxic gamma delta T cell reactivity has only been found against the highly homologous enterotoxins SEA and SEE. Finally, HLA-class II positive gamma delta T cell clones can present SE to other SE reactive T cells but appear to be relatively resistant to T cell mediated lysis. Taken together, TCR gamma delta positive T cells are able to respond to a number of bacterial superantigens and may therefore be involved in local immune responses to such antigens. This may be especially relevant for those gamma delta T cell subpopulations that are preferentially found in the (intestinal) epithelia where exposure to bacterial superantigens is likely to occur. PMID- 8467095 TI - Staphylococcal superantigens as inducers of signal transduction in MHC class II positive cells. AB - Staphylococcal superantigens (SEs and TSST-1) interact with and potentially activate two of the main subsets of the immune system: T lymphocytes and MHC class II-positive cells. Since the interaction of SEs and TSST-1 with MHC class II molecules is the first step in triggering immune cells activation, a detailed understanding of the nature of this interaction is essential for understanding its effect on the immune system and for designing therapeutic strategies for SEs and TSST-1-mediated injury. A series of events is induced in MHC class II positive cells (B cells, activated T cells, monocytes, and synoviocytes) upon engagement with superantigens. Some of these events require monomeric forms of superantigens, whereas others are critically dependent on cross-linking of toxin bound MHC class II molecules by a biochemical agent (biotin-avidin) or a natural physiological one such as the TCR. The ability of superantigens to induce polyclonal activation of MHC class II-positive cells may confer to the superantigen its capacity to trigger autoimmune diseases. PMID- 8467096 TI - Not every superantigen induces tolerance in vivo. AB - We have distinguished TSST-1 from SEA and SEB with respect to its in vivo effect on T cells, that is, SEA and SEB induce tolerance in treated mice whereas injection of TSST-1 does not result in tolerance. Therefore, previous observations which relate superantigens to the suppression of reactive V beta TCR T cells seem difficult to generalize to all bacterial superantigens. Since the effects of superantigens are beginning to be exploited for immunotherapy, the differences between TSST-1 and SEB in terms of induction of tolerance suggest that all superantigens may not generally be useful in this respect. Each superantigen obviously should be studied in vivo in respect to T cell tolerance induction. PMID- 8467097 TI - Do superantigens play a role in autoimmunity? AB - Mycoplasma arthritidis produces a typical soluble superantigen (SAg) which shares many characteristics with bacterial toxins and Mouse Mammary Tumor Virus SAg. However, this microbe is associated with an autoimmune-like disorder and this disease may therefore serve as a model to investigate the potential role of a SAg in autoimmune disease pathogenesis. PMID- 8467098 TI - Expression of hornet genes encoding venom allergen antigen 5 in insects. AB - Antigen 5, also known as Dol m V, is a major allergen found in the venom of the baldfaced hornet, Dolichovespula maculata. We have inserted the f10 and f17 cDNAs, which encode hornet antigen 5 (HA5) forms 2 (Dol m; VB) and 3 (Dol m VA), respectively, into the genome of the baculovirus, AcMNPV, to produce the recombinant baculovirus gene expression vectors, vEV-HA5f10 and vEV-HA5f17. Insect cells infected with either vEV-HA5f10 or vEV-HA5f17 produce and secrete a novel protein with an electrophoretic mobility which is similar if not identical to authentic mature Dol m V. The gene products also react specifically with a polyclonal antiserum raised to Dol m VB as expected. Dol m V gene products were not acutely toxic when injected into insect larvae. However, infection of fifth instar larvae with vEV-HA5f17 resulted in premature melanization of the larvae and lower weight gain than infection with control virus. Thus, the Dol m V gene product has a subtle, possibly cytotoxic or biochemical effect on insects. The expression systems may prove useful in further structural and functional characterization of these proteins. PMID- 8467099 TI - Development of recombinant viral insecticides by expression of an insect-specific toxin and insect-specific enzyme in nuclear polyhedrosis viruses. AB - As supplements to classical chemical insecticides, two approaches to develop recombinant baculovirus insecticides are described. In one approach an insect specific toxin is expressed leading to a dramatic reduction in time to death. In the second approach an insect juvenile hormone esterase is expressed which leads to a reduction in feeding. Modifications of the wildtype esterase led to viruses which reduced the time to death as effectively as did the toxin-expressing virus. In both cases existing recombinant viruses are viewed as leads, and approaches to further improvement in the engineered viruses are suggested. Many of these approaches are based on analogy with the development of classical synthetic insecticides. Using these viruses as examples, the potential utility and limitations of recombinant viruses and other biological insecticides are discussed. PMID- 8467100 TI - Delayed and enhanced biodegradation of soil-applied diphenamid, carbendazim, and aldicarb. AB - Recent studies have demonstrated that interaction between various agrochemicals and soil microorganisms may either slow down or enhance processes of degradation. Soil disinfestation is employed for the control of soil-borne pathogens and weeds. Soil application of such broad-spectrum biocides, as well as some more selective chemicals, has a strong effect on microbial activity, which may result in drastic reduction in the rate of degradation of pesticides applied to such treated soils. Application of pesticides to previously disinfested soils may extend their biological activity, which in the case of herbicides could cause phytotoxic damage to the next crop. In contrast, repeated application of the same or structurally related pesticides may result in a selective buildup of microbial populations capable of degrading the pesticide at much faster rates. Cases of accelerated degradation were reported for pesticides belonging to various chemical groups. Studies were conducted to evaluate the mechanisms of accelerated degradation. For several pesticides it has been shown that soil fungi are involved in their normal degradation, but not in their accelerated degradation. The shift in the rate of degradation of pesticides such as diphenamid, benomyl, and S-ethyl dipropylthiocarbamate, in soils that have acquired accelerated degradation, seems to be associated with the buildup of populations of bacterial degraders. Moreover, it has been shown that for the herbicide diphenamide, accelerated degradation is apparently linked to the induction of an oxidative demethylation process in soil bacteria, which might be analogous to the development of resistance in pests. Contrary to studies demonstrating accelerated degradation of the systemic insecticide aldicarb and accumulation of aldicarb sulfoxide in non-history soils, our work has shown that repeated application of this carbamate at several locations in Israel over a 10-year period did not induce accelerated degradation. It should be pointed out that in the Israeli soils there was only minimal formation of aldicarb sulfoxide. These studies were performed in soils with a pH ranging from 7.8 to 8.3, which is higher than the pH reported for soils where accelerated degradation was detected. PMID- 8467101 TI - Temperature rise in tumor tissue during high-dose-rate photoradiation. AB - The bioheat transfer equation and optical diffusion theory are used to develop a mathematical model for describing the thermal field in a spherical tumor and its surrounding normal tissue resulting from photoradiation. Analytical solutions to the model equations are presented for determining both the steady-state and transient temperature profiles. The effect of the optical and thermal properties of the surrounding normal tissue on the thermal field generated within the tumor is explored. PMID- 8467102 TI - Mathematical study of periodic breathing as an instability of the respiratory system. AB - A theoretical study of respiratory stability, based on a simple CO2 model of the respiratory system, investigates each component of respiration: the plant system and the central and peripheral controller systems. Analysis of the dynamic properties of the plant leads to a simplified respiratory model for the study of the influence of the central and peripheral controller components on stability. It is shown that the central component is not involved in respiratory instability phenomena such as periodic breathing whereas the peripheral component plays a major role. The explicit analytical index of stability obtained allows definition of the conditions of occurrence of periodic breathing in terms of the fundamental respiratory parameters. Moreover, this index can be used to evaluate the influence of various respiratory parameters on the stability of respiration. PMID- 8467103 TI - Mathematical description and computer simulation of retinal cometlike afterimages: a modified neural equation with stability analysis. AB - A mathematical model for the spatiotemporal description of a well-known psychophysical phenomenon, the cometlike afterimage effect (CLAIE), is presented. The CLAIE occurs when a bright circular light spot moves slowly in the peripheral human retina. Under these conditions, the leading edge of the dot looks circular, but the trailing edge becomes elongated like a comet's tail whose length increases with speed and luminance, and the illusion is more prominent for photopic backgrounds. This cometlike motion smear is described on the basis of the temporal responsiveness and adaptation of rods. The model is an extension of an existing neural model of M. N. Oguztoreli et al., with an additional term that allows prolonged saturation and long decay time following exposure to intense stimuli, and these effects are held responsible for the cometlike smear. The model predicts the response of photoreceptors through a nonlinear ordinary integrodifferential equation, which includes known biophysical terms for response dynamics, adaptation, saturation, and kinetics of intermediate components of the phototransduction process. The introduction of a saturation coefficient into the neural equation makes it possible to distinguish the different saturation thresholds of the rod-and-cone system. Numerical determination of the stationary solutions and complete linear stability analysis of the improved neural equation are given for a neuron of second order, and some computational results are presented for phase flows around different singular points in the phase field. A computer simulation based on the improved neural equation is presented for modeling the development and features of the CLAIE as a function of the speed and luminance of the stimulus and the background intensity. The computational results agree well with the psychophysical findings relating to the CLAIE. PMID- 8467104 TI - Complications of enteral feeding. PMID- 8467105 TI - Chronically increased vitamin intake and vitamin status of healthy men. AB - The effects of an 8-wk chronically increased vitamin intake on the biochemical parameters of vitamin status in 498 healthy men were estimated. A control group of 520 volunteers, given a placebo instead of vitamins, was also examined to control the changes that occur in biochemical vitamin supply parameters. Comparison of the measurements between the groups showed that plasma concentrations of folate, vitamin B12, and tocopherol; the urine concentrations of thiamine and riboflavin; and the activities of measured vitamin-related enzymes increased linearly and independently to the baseline vitamin status by the absolute value. Plasma concentrations of ascorbic acid, activity coefficients, and urinary excretion of 4-pyridoxic acid increased more in men with lower baseline values. The plasma retinol concentration did not change despite doubling the vitamin A intake. PMID- 8467106 TI - Glucose and fat utilization during intravenous administration of glucose and lipid emulsion in non-insulin-dependent diabetic patients. AB - To evaluate the clinical significance of substrate competition in the insulin resistant state, we measured glucose and lipid utilization in 10 non-insulin dependent diabetic patients during an isoglycemic hyperinsulinemic (approximately 75 and approximately 1500 mU/L) clamp without and with the concomitant infusion of Intralipid (0.15 g triglycerides.kg-1 x h-1) and during Intralipid infusion only in combination with indirect calorimetry. We found that a lipid emulsion does not alter the metabolic clearance rates of glucose at insulinemias of approximately 75 mU/L (5.58 +/- 2.56 vs. 6.03 +/- 2.43 ml.kg-1 x min-1) and approximately 1500 mU/L (13.55 +/- 3.17 vs. 13.75 +/- 4.36 ml.kg-1 x min-1) and it does not change oxidative and nonoxidative glucose disposal rates. Insulin and glucose attenuate the Intralipid-induced increase in serum triglycerides, free fatty acids, and lipid oxidation. We conclude that, whereas Intralipid infused at a standard rate does not decrease glucose utilization under hyperinsulinemic conditions, its own removal from the plasma is enhanced by glucose and insulin in non-insulin-dependent diabetic patients. PMID- 8467107 TI - Long-term serum lipid lowering, behavior modification, and weight loss in obese women. AB - Reduced calorie intake, changes in the composition of foods ingested, and increased physical activity are the usual initial recommended therapies for the obesity that often accompanies hypercholesterolemia and other hyperlipidemias. Collectively resulting in weight loss, these behavioral changes are known to produce short-term (< or = 7- to 9-mo) reductions in serum cholesterol and other lipids. In contrast, previous long-term (> or = 1-yr) investigations fail to disclose a cholesterol-lowering effect of weight loss, although the subjects in these studies were not hypercholesterolemic. The aim of our investigation was to examine the long-term changes in serum lipids that occurred in a representative cohort of healthy obese (n = 45, body mass index mean +/- SD 39.0 +/- 8.6 kg/m2) women after they completed a 15-wk conventional behavior-modification program. The serum cholesterol level of this cohort was elevated at baseline (6.18 +/- 1.41 mM, > or = 75th percentile). At the time of follow-up (17.0 +/- 7.0 mo), there were significant decreases in body weight (-16.7 kg, p < 0.001) and reductions in serum total (-0.53 mM, p < 0.01) and low-density lipoprotein (-0.35 mM, p < 0.05) cholesterol. Serum triglyceride levels also decreased significantly (-0.38 mM, p < 0.001), and serum high-density lipoprotein levels remained unchanged; the ratio of high-density lipoprotein total cholesterol increased significantly (p < 0.05) relative to baseline levels. Multiple stepwise regression analysis indicated that the best predictor of percentage change in each respective lipid was its own baseline level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467108 TI - Parenteral nutrition in hyperemesis gravidarum. AB - Hyperemesis gravidarum (HG) is a clinical condition that threatens fetal viability and even the mother's life when the severity of symptoms almost completely prevents the intake of food. Parenteral nutrition (PN) is a possible alternative. We present eight patients with HG. There were 10 PN treatments because two of the patients required the treatment twice. There were 9 central venous and 1 peripheral treatment delivery. The average age of the patients was 27.5 yr. Gestational ages varied from 8 to 19 wk. PN treatments were formulated as amino acid and glucose solutions (fat emulsions in 2 of the 8 cases) blended with vitamins and electrolytes. These treatments lasted 5-16 days. Before PN deliveries were initiated, five of the patients presented some degree of protein calorie and/or visceral protein malnutrition. All of them showed minor liver dysfunction, which did not change during PN. Newborns were term deliveries, except for one case of missed abortion. Results show that PN constitutes a therapeutic alternative in cases of HG that do not respond to the standard treatment of parenteral hydration and antiemetics. In fact, symptoms disappear promptly, and no significant complications arise. PMID- 8467109 TI - Substrate supply as determinant of O2 extraction in sepsis and nonseptic trauma. AB - Metabolic and hemodynamic measurements performed in 72 septic (S) and 40 nonseptic (NS) surgical patients undergoing total parenteral nutrition were analyzed to assess the role of substrate supply as a determinant of O2 extraction (O2Ex). In S, O2Ex was inversely related to cardiac index (CI); at any given CI, significant increases in O2Ex with simultaneous increases in O2 consumption (VO2) were related to increasing doses of amino acids, with a less remarkable effect of fat and no effect of glucose dose. In NS, O2Ex was also inversely related to CI; however, at any given CI, there was no evident substrate-supply dependency of O2Ex, which was more normally related to P50. The increase in VO2 per gram of administered amino acids, at any CI and O2 transport index, was 817 ml in S and 267 ml in NS. These results suggest that the impaired O2Ex and VO2 in S may at least partly reflect abnormalities in substrate utilization and that amino acid support may have a role in modulating these abnormal O2Ex patterns by providing preferential substrate for oxidative metabolism. PMID- 8467110 TI - Amino acid imbalance and intracellular protein synthesis. AB - The effects of amino acid imbalance, created by decreasing the concentrations of specific amino acids in culture media, on intracellular protein synthesis were compared with the findings obtained by restricting all amino acids. Protein synthesis levels were estimated by measuring the uptake rates of 14C-labeled amino acids by cultured rat hepatoma AH109A cells. The inhibitory activity of a 0.1-fold dilution of valine in DM-160 medium was higher than that resulting from the dilution of all amino acids by 0.1-fold. On the other hand, the dilution of other essential amino acids was not as effective as the dilution of all amino acids, whereas the concurrent dilution of valine and leucine was found to be equivalent in effectiveness to the latter. Protein-synthesis levels in 0.3, 0.1, 0.03, and 0.01 mM valine were maximum at 0.9, 0.3, 0.09, and 0.03 mM leucine, respectively. Valine transport into the cell was found to be inversely proportional to the extracellular leucine concentration. DL-Norvaline and DL norleucine were not effective. Valine-leucine interactions were suggested to be involved in intracellular protein synthesis. PMID- 8467111 TI - Nutrition behavior of malnourished HIV-infected patients and intensified oral nutritional intervention. AB - Malnutrition and cachexia are characteristic symptoms of human immunodeficiency virus (HIV)-1 infection and AIDS. To identify risk situations that might affect nutritional behavior and status and to evaluate the therapeutic effect of an intensified oral nutritional intervention, we analyzed 81 consecutively treated homosexual HIV-infected outpatients with malnutrition retrospectively and could follow the outcome of a nutritional intervention prospectively in 54 of them. Nutritional therapy was ineffective for only 5 of the 54 patients; constant weight loss could be stopped in 31 of the patients, and 18 patients could even gain weight. We suggest intensified oral nutritional intervention should be an integral part of the treatment of HIV-infected patients to prevent or treat malnutrition. PMID- 8467112 TI - Nutrition management in acute renal failure. AB - A case report is presented in which a man developed acute renal failure after a surgical misadventure. The initial management, postoperative course with the manifestation of acute tubular necrosis with oliguria and its physiological sequelae, nutrition management in the context of the overall treatment, hospital course, and patient's disease are discussed in detail. The rationale for giving nutrition support, the general considerations for providing nutrients, and the specific nutrition considerations as they pertain to the patient under discussion are outlined to provide a comprehensive guide and overview of the nutrition management of a patient with acute renal failure. PMID- 8467113 TI - Carbohydrate metabolism and requirements for nutritional support: Part I. PMID- 8467114 TI - Can O2-extraction pattern be altered in sepsis by substrate availability? PMID- 8467115 TI - Dietary L-lysine supplementation: a promising nutritional tool in the prophylaxis and treatment of osteoporosis. PMID- 8467116 TI - Is normal normal? PMID- 8467117 TI - Classic human vitamin C depletion experiments: homeostasis and requirement for vitamin C. PMID- 8467118 TI - Metabolism of ascorbic-1-14C acid in experimental human scurvy. 1969. PMID- 8467119 TI - PUFA 1992. Fifth Scientific Meeting of the Society for Research on Polyunsaturated Fatty Acids. November 11-14, 1992, Tokyo, Japan. Abstracts. PMID- 8467120 TI - [Sentinel practice data quality. Denominator concepts, spatial and temporal frequency patterns. Special issue following the "1st Sentinel-Workshop Hannover" on 29 April 1992]. PMID- 8467121 TI - [Data quality in the MORBUS Sentinel Project--expiratory wheezing in infants]. AB - Since 1991 the MORBUS project is being conducted to establish and run a sentinel network of 100 general and paediatric practices in three regions of Germany. A number of health conditions have been and will be monitored consecutively with special emphasis on environmentally determined health problems. From March to June, 1991, 1054 contacts of 1- and 2-year-old children with expiratory wheezing were reported. Quality of these event data was assessed by means of internal completeness. Important clinical information was missing in about 10% of all cases without evidence for regional differentiations. Data quality by this criterion was better in first contact than in re-contact cases (9.7% vs 18.1% missing). Questions concerning the parents (allergies, smoking, education) were less frequently answered (up to 24% missing) than questions of obvious medical relevance to the child. Completeness of parental information varied considerably between regions. There was no association between the medical specialty of the doctors and the quality of their data. In a longitudinal view, there was a slightly positive trend over time in the proportion of clinically incomplete case reports at borderline statistical significance (p = 0.057). Apart from these minor findings then, there was an overall good consistency of completeness in the MORBUS data on expiratory wheezing. By optimizing questionnaires and data transmission, it should be possible to increase the data quality even further. PMID- 8467122 TI - Numerators and denominators of rates estimated on the basis of physicians' practice data. AB - The paper discusses selected methodological aspects of numerators and denominators derived from medical practice observations. The estimation of rates (of incidence or prevalence) on the basis of primary care practice data is apt to be influenced by several methodological factors. These are: morbidity of the local population, physician workload and expertise, diagnosis coding rules, and patient visiting behavior (Anderson, 1984). These factors tend to have an impact on the numerator. Vis-a-vis the lack of appropriate population denominators of single practices, the question is whether rate estimates may be developed for fee for-service systems without population registration of persons with medical practices and which use these rates may be put to. PMID- 8467123 TI - Quality of care in general practice and a fixed denominator. AB - The NHG, the college of general practitioners in the Netherlands, has developed a national programme of standard setting in which 25 standards have been published since 1989 on quite different subjects. Its ultimate goal is to improve the quality of care in general practice. Both health insurance companies and governmental organizations are very interested in all the aspects of quality assurance and assessment allied with the programme. The fixed denominator for general practice in the Dutch health care system is of essential value with regard to the selection of topics to be standardized, the evaluation of the programme and the investigations into the consequences of the introduction of standards. Its role is demonstrated and discussed as a modal example. PMID- 8467124 TI - [Estimating the denominator of a sentinel practice using accounting data of the federal physicians association]. AB - In order to interpret the regional and temporal variation in the number of cases reported for sentinel topics, rates have to be calculated which relate these figures to a common denominator. For this denominator different definitions are possible, where this paper focuses on the contact denominator, counting all contacts between the patient and the doctor in a specified period of time and a specified population (i.e. children between 2 and 3 years of age by sex for the first MORBUS topic). One patient may produce different contacts. Due to work load considerations contact denominators could not be directly recorded in sentinel practices in the MORBUS-project. A method was developed which combined minimal denominator information obtained from sentinel practices with routine (accounting) data from the doctor's associations, in order to estimate denominators with a high degree of precision. Data elements in the accounting data base include number of personal patient-doctor-contacts by type of treatment (screening/cure/emergency/referral) and insurance status (ordinary member, family member, retired) itemized list of actions that were reimbursed through the insurance company structural data about the doctor/practice (specialty, accreditation date) etc. For a first assessment of the degree of accuracy with which denominators can be estimated by such data, a pilot test was scheduled for April 1991. Doctors recorded the number of contacts with children between two and three years of age (by sex) for one week on a simple checklist. A linear model which included specialty, region, number of vouchers per quarter, number of infant health assessments and date of accreditation as predictors, was fitted to the data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467125 TI - Validation of sentinel data. AB - The Dutch Sentinel Practice Network, "de Peilstations" started in 1970. The purpose of this network is to gain a better insight into the epidemiology of a number of illnesses and conditions as they are presented to the general practitioner. The network is sponsored by the Ministry of Welfare, Public Health and Culture. Value was attached to the distribution of the spotter physicians over the country and by degree of urbanisation. The presence of 1% of the population of the four provinces groups and the three urbanisation groups has been observed in the practices of the spotter physicians. The completeness of the registration, the internal and the external validity of the data collected by the physicians are discussed. PMID- 8467126 TI - [A method for determining the denominator in general practice--results of a pilot study]. AB - In countries with fee for service billing and direct access to specialist care the general practitioner does not know key figures of the population he serves. As the role of general practice in health-service-research, quality assurance activities and the construction of sentinel-networks is becoming more important, valid methods to determine the denominator are needed. Results from five practices suggest that yearly contact groups should be used as a common denominator for general practice in our health care system. For certain groups of patients (e. g. the elderly > 60 yrs.) even quarterly contact groups can give sufficient information to forecast the yearly contact group. PMID- 8467127 TI - [Incidence of findings in pediatric sentinel practices: the Hamburg-Harburg pilot project]. AB - In a one year pilot project in Hamburg, the feasibility of a sentinel practice system was tested by paediatricians and the health officials. The items to be documented were four symptoms of possible allergic pathogenesis. The mean of contacts per practice and week was 42 for rhinitis, 9 for wheeze, 8 for acute conjunctivitis and 4 for urticaria. Rhinitis, conjunctivitis and wheeze showed clear seasonal trends, but also shortterm peaks running against the seasonal trends were detectable. Seasonal covariations between symptoms and environmental parameters were strongest between wheeze, temperature and sulfur dioxide concentration of the air. But only a part of the wheeze-peaks followed peaks of temperature or sulfur dioxide. The implications of the feasibility study results for a long-term sentinel system in Hamburg are discussed. PMID- 8467128 TI - [Asthma attacks in general practice--epidemiologic markers and seasonal patterns in longitudinal observation]. AB - The continuous registration of asthmatic attacks by the Swiss Sentinel Network "Sentinella" since November 1988 has been preceded by a pilot study which tested the methods of data collection and analysis. The original aim was (a) to use the incidence of asthmatic attacks as a possible indicator for the adverse effects of rising concentrations of air pollutants, and (b) to create a set of baseline data for future research in this field, i.e. data of asthmatic attacks for retrospective analysis of periods with increased levels of air pollution. Here, morbidity characteristics and seasonal patterns of asthmatic attacks as registered from November 1988 to May 1991, will be presented only. With regard to age and sex the data show that more than half of all asthmatic attacks occurred in children 0-14 years of age. Males outweigh females by roughly two to one, but the distribution becomes more even after adolescence. These results are in accordance with the literature (Table 1). Whereas hospital beds (hospitalisations) are occupied by a growing number of patients suffering from asthma, especially in children hospitals, the referral rate of children with asthmatic attacks by primary car physicians has remained relatively steady over the past three years (Table 2). Thus, it can be inferred that asthma, while a major problem in the hospital, is dealt with successfully by practitioners in the primary care setting. This is to the contrary of international trends which show an increasing referral rate for asthma. A differential analysis of workload from asthmatic attacks for general practitioners, internists and paediatricians is directing toward a rising incidence of asthma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467129 TI - [The European study for counseling in HIV antibody testing in general practice: results of the German project section]. AB - General practitioners play an important role in counselling for HIV-Tests. There is little known yet about the background of the decision process which results in doing the HIV-test. The EUROSENTINEL-study on requests for HIV-testing started in 1990 and is in the meanwhile carried out in 7 sentinel-networks in six european countries. In the beginning of 1991 the german part started in 36 practices in the north of Hessia. In the first year of the study these 36 practices recorded 327 consultations about HIV-testing. The initiative to counsel was taken in 64.2% by the patient and in 35.8% by the doctor. In male patients the main reasons for the consultation were heterosexual contacts and administrative or legal reasons. In female patients it were fear of HIV-infection without any risk and professional exposure. In 86.2% of patients the consultation was followed by a HIV-test. Seven Tests (2.5%) were positive. All HIV-positive patients belonged to the classical risk groups. The results are discussed in comparison to those of other european networks. It can be concluded that general practitioners play an important role in primary prevention of HIV-infection and in counselling people who are worried by the AIDS epidemic. PMID- 8467130 TI - Organochlorine pesticide residues in black tea, camomile, and linden. PMID- 8467131 TI - Microbial abundance and degradation of polycyclic aromatic hydrocarbons in soil. PMID- 8467132 TI - Movement of pendimethalin in soil of the south of France. PMID- 8467133 TI - Degradation of 14C-glyphosate in Saskatchewan soils. PMID- 8467134 TI - Biodegradation of liquid and microencapsulated formulations of alachlor in a clay loam soil. PMID- 8467135 TI - Chromium, copper, and zinc concentrations in edible vegetables grown in Tarragona Province, Spain. PMID- 8467136 TI - Biodegradation of anthraquinone dyes by Bacillus subtilis. PMID- 8467137 TI - Phthalate esters as potential contaminants during GC analysis of environmental samples using electron capture and mass spectrometric detectors. PMID- 8467138 TI - Influence of lead on pregnant women in metropolitan Mexico City. PMID- 8467140 TI - Cadmium, lead, and zinc concentrations in human fingernails. PMID- 8467139 TI - Organochlorine insecticide residues in human breast milk: a survey of lactating mothers from a remote area in Papua New Guinea. PMID- 8467141 TI - Effect of 2-thiotriazone (TTZ) on hepatic and pulmonary glutathione (GSH) concentrations in rats. PMID- 8467142 TI - Effects of environmental cadmium pollution in fattening of veal calves. PMID- 8467143 TI - Effect of alachlor on the urinary excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone by rats. PMID- 8467144 TI - Bioaccumulation and elimination of endosulfan in the fish yellow tetra (Hyphessobrycon bifasciatus). PMID- 8467145 TI - Bioconcentration and excretion of diazinon by eel. PMID- 8467146 TI - Plasma sorbitol dehydrogenase, glutamate dehydrogenase, and alkaline phosphatase as potential indicators of liver intoxication in grey mullet (Mugil auratus Risso). PMID- 8467147 TI - Variable sensitivity of Cyprinus carpio eggs, larvae, and fry to pesticides. PMID- 8467148 TI - Effect of copper on the growth of Anacystis nidulans. PMID- 8467149 TI - Stage-dependent susceptibility of Bufo arenarum embryos to cadmium. PMID- 8467150 TI - Mercury concentrations of walleye (Stizostedion vitreum vitreum) in 34 northern Wisconsin lakes. PMID- 8467152 TI - Metal concentrations in American lobster and channeled whelk from two dredge spoil dump sites in Long Island Sound. PMID- 8467151 TI - Heavy metals and polycyclic aromatic hydrocarbons (PAH's) in marine organisms from the Ionian Sea (Italy). PMID- 8467153 TI - Changes in the blood endotoxin concentration after digestive surgery. AB - Blood endotoxin concentrations measured in 57 patients with digestive disorders pre- and postoperatively, were found to peak one day after surgery, then gradually return to the preoperative level. The plasma endotoxin concentration was not significantly different in patients with and without liver cirrhosis before surgery, but was significantly higher in the cirrhosis group one day after surgery. The preoperative endotoxin concentration did not correlate with the white blood count (WBC), platelet count, or routine biochemical liver function tests, however, a significant negative correlation was observed between the plasma endotoxin and fibronectin concentrations. The ability of plasma to inactivate endotoxin was quantified by serial measurements of the endotoxin concentration following the addition of a known quantity to each patient's plasma. The plasma from normal subjects quickly inactivated endotoxin, but inactivation was decreased in the plasma from patients with liver failure. PMID- 8467154 TI - Thoracic endoscopic T2-T3 sympathectomy in palmar hyperhidrosis: experience of 112 cases. AB - Palmar hyperhidrosis is a troublesome and embarrassing disorder that causes professional, psychological, and social handicaps. Its etiology is unknown, although surgical treatment by thoracic sympathectomy is presently believed to be the best method of cure. Up to now, numerous methods of sympathectomy, including open thoracotomy, as well as posterior and supraclavicular approaches have been described. We favor endoscopy at this time due to both its simplicity and its resultant short hospital stay. During the period between March 1988 and October 1990, 112 patients (55 males, 57 females) suffering from palmar hyperhidrosis underwent 222 thoracoscopic T2-T3 sympathectomies under general anesthesia in our department. The remaining 2 hands had a second operation of unilateral open thoracotomy due to pleural adhesion. The patients' ages ranged from 15 to 45 years. A total of 220 hands became dry while the others showed improvements. There were 5 patients who required unilateral chest tube insertion, 2 for post thoracotomy drainage and 3 for intrathoracic hemorrhage after thoracoscopic pneumonolysis. The average operative time (bilateral) was 30.8 min and hospital stay was 2.87 days. Compensatory hyperhidrosis was the major complication. There was no mortality. We therefore consider thoracoscopic sympathectomy to be a simple, safe, and effective method for treating palmar hyperhidrosis. PMID- 8467155 TI - Sequential bypass for multisegmental occlusive disease. AB - We evaluated the effectiveness of a sequential bypass for multisegmental occlusive disease. Forty-seven multiple bypass grafts were performed on 43 patients ranging in age from 55 to 83 years (mean: 70 years). The indications for operation included incapacitating claudication in 20 limbs, resting pain in 15, and nonhealing ulcers in 12. An anatomical arterial bypass was performed on 36 limbs, consisting of an aorto-femoro-popliteal bypass in 21 limbs, a femoro popliteal-posterior tibial bypass in 8, an ilio-femoro-popliteal bypass in 4, an ilio-femoro-posterior tibial bypass in 2, and a femoro-popliteal-plantar bypass in 1. Similarly, an extra-anatomical arterial bypass was performed on 11 limbs, consisting of an axillo-femoro-popliteal bypass in 6, a crossover femoro-femoro popliteal bypass in 3, an axillo-femoro-posterior tibial bypass in 1, and a crossover femoro-femoro-anterior tibial bypass in 1. The follow-up period ranged from 3 to 77 months (mean: 23 months). Twelve graft failures occurred, and 2 of them required major amputations. The cumulative graft patency rate was 85% at one year and 65% at 3 years. Arterial Doppler examination revealed a mean preoperative ankle-brachial index of 0.29 +/- 0.25. The early and late mean postoperative ankle-brachial indices, however, increased to 0.97 +/- 0.19 and 0.84 +/- 0.25, respectively. Midterm results have indicated that such multiple sequential bypass grafts are effective. PMID- 8467156 TI - Comparison of postoperative results following terminal esophagoproximal gastrectomy and esophageal transection for esophageal varices. AB - The results of 44 terminal esophagoproximal gastrectomies (TEPG) and 53 esophageal transections (ET) for esophageal varices, performed during the period between January, 1975 and March, 1989, were retrospectively compared. The results examined prognosis, recurrence of esophageal varices and late postoperative complications. The 5-year survival rates for patients who underwent selective or prophylactic surgery were 85.9% following TEPG and 81.6% following ET. However, the 10-year survival rate for the former group was significantly lower than that for the latter group at 59.3% versus 70.0% (P < 0.05) because of the number of deaths due to hemorrhage and liver failure caused by anastomotic ulcers. The respective 5-year recurrence rates of varices for the TEPG and ET groups were 18.4% and 26.4%, respectively, while the 10-year recurrence rate for the former group was again significantly lower than that for the latter group at 27.1% versus 53.7% (P < 0.01). As for postoperative late complications, reflux esophagitis and/or anastomotic ulcers were found twice as frequently after TEPG as after ET. Thus, although TEPG was more effective for preventing variceal recurrence it left the potential for an anastomotic ulcer to develop, which was the dominant cause of death more than 5 years after surgery. PMID- 8467157 TI - Extra-anatomic bypass for aorto-iliac occlusive disease in octogenarians. AB - Fifteen patients over 80 years of age with aorto-iliac occlusive disease (AIOD) underwent surgical revascularization of an ischemic lower extremity by extra anatomic bypasses. The mean age at operation was 81.7 years, ranging from 80 to 86 years. Surgical revascularization of the ischemic lower limbs could safely be performed with an extra-anatomic bypass in these patients without any major complications. The mean follow-up period was 32.7 months. Eight patients died during the follow-up, only one of them died from myo-nephropathic metabolic syndrome related to acute graft occlusion. As a long-term result, the cumulative survival after 37 months was only 23.9%, while the actual graft patency rate was 43.8% after 60 months in this series. The survival period with an improved quality of life after surgical intervention reached a level of approximately 40% of that for the general population. There should be no hesitation over whether to carry out surgical intervention for AIOD in patients over 80 years of age, because a reasonable extension of life can be obtained by an extra-anatomic bypass. PMID- 8467158 TI - Effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in patients with gastric cancer. AB - The effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in gastric cancer patients was investigated. A 2-mg dose of lentinan was administered to 12 patients intravenously twice, the first at 3-9 days before and the second the day before surgery. The results were then compared with a control group without lentinan administration comprising 12 patients. Regarding peripheral blood and lymph nodes without metastasis, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu7, and anti-Leu11 were analyzed by flow-cytometry. As for tumor tissues, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu11, and anti-M3 were analyzed after immunohistochemical staining. There were no significant changes in the lymphocyte subsets of peripheral blood between the two groups. In the lymph nodes, the CD4 cell ratios increased; otherwise in regard to tumor-infiltrating lymphocytes (TILs), the number of CD4, Leu11 and LeuM3 cells showed a prominent increase. Therefore, lentinan was observed to produce different effects in accordance with the subjective organs. PMID- 8467159 TI - Rat liver peroxisomal and mitochondrial fatty acid oxidation in sepsis. AB - Time course changes in hepatic mitochondrial and peroxisomal fatty acid oxidative capacities, as well as changes in the related enzyme activities, were investigated in rats with sepsis induced by cecal ligation and puncture. Palmitoyl-L-carnitine oxidation was not altered, but carnitine palmitoyl transferase (CPT) dependent palmitoyl-CoA (plus L-carnitine) oxidation was slightly increased in the liver mitochondria of the septic rats. Hepatic CPT activity, being the rate-limiting step of mitochondrial beta-oxidation, was also enhanced by sepsis. In contrast, cyanide-insensitive peroxisomal beta-oxidation and the carnitine acetyltransferase and catalase activities associated with the peroxisomal-enriched fraction were markedly reduced by abdominal sepsis. Cyanide insensitive beta-oxidation in control livers showed optimal specificity for lauroyl- and myristoyl-CoA and this pattern remained unchanged by sepsis. However, oxidation rates were reduced for all acyl-CoA esters tested, being more pronounced with longer carbon chain length acyl-CoA substrates. These results indicate that in early sepsis, hepatic mitochondrial fatty acid oxidative capacity was increased, probably due to enhanced CPT activity, whereas peroxisomal beta-oxidation was seriously disturbed along with reduced catalase activity. PMID- 8467160 TI - Aberrant retrotracheal goiter: report of a case. AB - A case of intrathoracic retrotracheal goiter in a 40-year-old woman is herein described. A computed tomographic scan, magnetic resonance imaging and endoscopical ultrasonography all confirmed the existence of a retrotracheal encapsulated lesion, which was suspected to be aberrant mediastinal goiter. Radioiodine scintigraphy, however, demonstrated little uptake in the mass. A large (7 x 6 x 4 cm), encapsulated adenomatous goiter was then easily removed via a right thoracic approach. PMID- 8467161 TI - A case of renal cell carcinoma with metastasis to the thyroid gland and concomitant early gastric cancer. AB - Metastatic lesions from renal cell carcinoma are commonly recognized in the lung and bone, however, thyroid metastasis has rarely been reported in the literature. We present herein a case of a man with lung and thyroid metastatic tumors from renal cell carcinoma. Although making a preoperative diagnosis of thyroid metastasis is difficult because there is no established diagnostic criteria, we were able to identify this thyroid lesion as a metastatic tumor from renal cell carcinoma by the pathological findings. Interestingly, hypercalcemia was recognized in this patient whose serum parathyroid hormone (PTH) level was not increased. Moreover, this patient also had early gastric cancer simultaneously, being a so-called 'double cancer'. After surgical resection of the right kidney and stomach, interferon was administered without any efficacy against the metastatic lesions of the lung and thyroid gland. PMID- 8467162 TI - A case of bilateral obturator hernias: image diagnosis and description of a retropubic operative approach. AB - A case of bilateral obturator hernias which was diagnosed by ultrasonography (US) and computed tomography (CT), and repaired by a retropubic extraperitoneal operative approach under spinal anesthesia is reported herein. A 91-year-old woman presented with lower abdominal and left groin pain consistent with a Howship-Romberg sign. US demonstrated an image of the bowel projecting from the small pelvic space to the left thigh with a to-and-fro movement of the bowel contents. The definitive diagnosis of an incarcerated left obturator hernia was made by CT which also revealed a mass in the right obturator foramen. Surgery was performed through a retropubic extraperitoneal approach under spinal anesthesia. No necrosis was observed in the incarcerated bowel and resection was not necessary. A simple hernial sac was found in the right obturator canal. The operation using the retropubic extraperitoneal approach was successful and we believe it to be the most effective procedure for obturator hernias which have been diagnosed early. PMID- 8467163 TI - The solitary cutaneous metastasis of asymptomatic colon cancer to an operative scar. AB - Although umbilical or cutaneous metastases from asymptomatic internal malignancies are occasionally documented, the literature contains no report of a solitary cutaneous metastasis to an old operative scar from an asymptomatic internal malignancy. A rare case of colonic cancer presenting as a solitary subcutaneous metastasis to a lower abdominal scar resulting from an open prostatectomy is described in this communication. It was impossible to distinguish this subcutaneous metastasis from a pyogenic granuloma caused by residual sutures without histological evidence. Thus, a granuloma that persists despite repeated treatment may be a possible sign of asymptomatic internal malignancy. PMID- 8467164 TI - Case report of an anomalous arrangement of the pancreaticobiliary ducts and nuclear DNA ploidy analysis. AB - Two cases with an anomalous arrangement of the pancreaticobiliary ducts (APBD) are reported in order to investigate the mechanism of carcinogenesis of the extrahepatic biliary tract from the aspect of DNA ploidy analysis. Highly elevated biliary enzymes were found in both cases. Although inflammatory changes without any metaplasia or neoplasia were observed histologically, a cytofluorometric nuclear DNA ploidy analysis showed an aneuploid low ploidy pattern in a histogram of the gall bladder, an aneuploid high ploidy pattern in a histogram of the common bile duct in one patient, and a diploidy pattern in the gall bladder, an aneuploid low pattern in the common bile duct in another case. These results may show that APBD may play a role in the development in DNA ploidy abnormality with refluxed pancreatic juice which may induce repeated irritation and inflammation. Radical surgery including a complete excision of the extrahepatic biliary tract followed by reconstruction may achieve better results with regard to undesirable consequences with an abnormal nuclear DNA ploidy pattern and decrease the likelihood of developing carcinoma. PMID- 8467165 TI - Portal vein calcification: a clinical review of the last 50 years and report of a case associated with dysplasminogenemia. AB - We report herein a case of a 68-year-old Japanese woman in whom calcification of the portal vein was recognized by plain abdominal X-ray radiograph and computed tomography (CT) scan when she presented with repeated thrombosis of the portal system. Following emergency small bowel resection for intestinal necrosis caused by superior mesenteric vein thrombosis, hematological studies revealed the association of dysplasminogenemia. A review of 21 cases of portal vein calcification reported between 1940 and 1990 revealed the average age to be 53.7 +/- 10.2 years and the male/female ratio 17:4. Although the majority of cases suffered from portal hypertension (81%), only 38% had any evidence of liver cirrhosis, while 52% had normal liver function, being comparable to idiopathic portal hypertension. The calcified lesions were located in the portal vein in 100% of cases, the splenic vein in 62%, the superior mesenteric vein in 33%, and the inferior mesenteric vein in 0%. The precise etiology of the calcification was not elucidated in any of the reviewed cases. The patient reported herein is the first reported case of portal vein calcification due to repeated thrombosis of the portal system caused by dysplasminogenemia, which could be accounted as a cause of idiopathic portal hypertension. PMID- 8467166 TI - The coexistence of abdominal aortic aneurysm and early gastric cancer: report of three cases. AB - The surgical approach for patients with abdominal aortic aneurysm (AAA) and coexistent abdominal malignancy remains controversial. We report herein three cases of coincident AAA and early gastric cancer, all of whom were treated by a two-stage operation and underwent curative surgery for their gastric cancer. The principles of our surgical approach are as follows: (1) the lesion which requires urgent surgery should be operated on first, and if both lesions show absolute indications, a one-stage surgical procedure should then be performed; (2) a two stage surgical procedure in which aneurysmectomy is performed first should be undertaken when no absolute indications for urgent surgery exist for either lesion; (3) a one-stage surgical procedure should only be performed when surgery on one lesion makes the other lesion highly dangerous; and (4) in patients with a poor prognosis because of far advanced cancer in whom the AAA shows no sign of rupturing, only a gastrectomy should be performed. PMID- 8467167 TI - Patients with multiple primary gastric cancers tend to develop second primaries in organs other than the stomach. AB - The multiple occurrence of a single cancer tends to result in the increased vulnerability of some other organs to another malignancy. In the present study, we examined a total of 1,606 patients with gastric cancer to ascertain whether the frequency of second primaries in organs other than the stomach is higher in patients with multiple gastric cancers than in those with a single gastric cancer. Primary cancers of other organs were present in 87 (5.9%) of 1,474 patients with single gastric cancer and in 16 (12.1%) of 132 patients with multiple gastric cancers. The difference was statistically significant. The most frequent site of the occurrence of a second primary was the colo-rectum, followed by the urogenital organs, uterus, breast, and lung in descending order of frequency. We therefore assume that the occurrence of multiple cancers in the stomach is not merely a chance phenomenon but is related to both genetic predisposition and environmental factors. PMID- 8467168 TI - The usefulness of postoperative continuous epidural morphine in abdominal surgery. AB - The influence of continuous epidural morphine on the recovery course of intestinal activity, urinary function, and ambulation after surgery was studied in 40 patients who underwent either gastrectomy for gastric cancer or cholecystectomy for cholelithiasis. Compared with a control group of patients whose postoperative pain was managed by pentazocine or hydroxyzine as before, the length of time before passing flatus or faeces was significantly shortened in the morphine groups (P < 0.05). Following gastrectomy, the urinary catheter was able to be removed significantly earlier in the morphine group (P < 0.05) although there was no statistical difference between both cholecystectomy groups. The morphine group experienced no difficulty with postoperative ambulation and exercise, although the difference in time before ambulation between the two groups was not considered significant. The results of this study led us to conclude that the postoperative continuous epidural infusion of morphine would be more beneficial following major abdominal surgery than the conventionally used methods of administering postoperative analgesia. PMID- 8467169 TI - The predictability of clinical antitumor effects using two distinctive in vitro chemosensitivity tests: an analysis of true positive cases. AB - The results of two types of in vitro chemosensitivity tests, namely, the human tumor clonogenic assay (HTCA) and the succinic dehydrogenase inhibition assay (SDIA), for solid tumors, including stomach, colorectal and lung cancers, were analyzed and their correlation with clinical effects evaluated. The anticancer agents employed were mitomycin C (MMC), 5-fluorouracil (5-FU), adriamycin (ADM) and cisplatin (DDP). The evaluability rates of the assays were 54.5% for HTCA and 89.0% for SDIA. Among the 29 cases with evaluable lesions subjected to HTCA, there were 4 true positives, 9 false positives, and 16 true negatives, whereas among the 32 cases subjected to SDIA, the corresponding numbers were 2, 6, and 24, respectively. There were no false negatives for either assay, the accuracy of prediction for HTCA being 69.0% and for SDIA, 81.3%. The true positives of both assays included one complete response (CR) and five partial responses (PR), although the eventual outcome was cancer death in all cases. Interestingly, in five out of the six true positive cases, the agent involved was either ADM or DDP, both the which are usually regarded as "second line" anticancer agents for gastrointestinal carcinomas. PMID- 8467170 TI - The quality of mass screening for breast cancer by physical examination. AB - Mass screening for breast cancer using physical examination alone has been carried out since 1983 in Zentsuji, Kagawa Prefecture, Japan. Over a 7-year period, breast cancer was detected in 11 of a total 8,271 examinees, the detection rate being high at 0.13%. The detected cases included a few early staged breast cancers, suggesting that mass screenings are of slight efficacy. Seven cases of interval cancer were found by breast self-examination after the mass screenings, supporting the value of breast self-examination. A relatively large number of interval breast cancers was detected in 1985 and 1986, when the rates of required further examination remained under 1%. The sensitivity and specificity of this screening were 61.1% and 94.5%, respectively, indicating a low sensitivity. These results suggest that the qualitative diagnoses made from the first screening by physical examination alone were often revealed to be false negatives. Therefore, the existing diagnosis should be employed in the first screenings. It is recommended that mammography be introduced to detect breast tumors which are nonpalpable or undetectable by physical examination alone. PMID- 8467171 TI - The zipper-mesh method for treating delayed generalized peritonitis. AB - Recently, many articles have been published related to the "open abdomen" concept which is performed particularly on patients with delayed generalized peritonitis. Since most arguments still support the effectiveness of this method and the results have been mostly favourable, it was decided to use the technique on 14 patients with peritonitis. Commercial zippers either with or without mesh were used on all. Four patients, however, died in the very early postoperative period and were excluded from the study. Others were examined as to the operative findings, period of delay, concomittant diseases, primary operations, indications of the technique, the number and type of the reinterventional procedures, status of remote organ failure, expected and realized mortality. Forty laparatomies were performed on 10 patients. In addition to obtaining a clean intraperitoneal cavity, some additional procedures such as anastomotic repair or gastroenterostomy could be done. The mean period of ventilator support was 27 h, the ambulation period was 3 days. The start of enteral nutrition early was able to be achieved more easily. In the patients whose expected mortality rate was as high as 70%-90%, a rate of 40% was established in those ten patients. PMID- 8467172 TI - The prognostic significance of DNA ploidy for neuroblastoma. AB - Flow cytometric DNA analysis was performed on 45 neuroblastomas in order to evaluate the prognostic significance of DNA ploidy. The DNA ploidy was diploid in 14 and aneuploid in 31 neuroblastomas and did not correlate with the conventional prognostic variables such as age, Evans' stage, or the primary site of the tumor. The survival of 31 patients with aneuploid tumors was comparable to that of 14 patients with diploid tumors. On the other hand, DNA aneuploidy was associated with a decreased long-term survival in 21 patients older than 24 months of age at the time of operation, and in 27 patients with advanced disease at Evans' stage III or IV. These results suggest that more intensive and longer-term postoperative chemotherapy is necessary for neuroblastoma patients older than 24 months of age, or for those with advanced disease if they have aneuploid tumors. PMID- 8467173 TI - Factors related to the recurrent hyperfunction of autografts after total parathyroidectomy in patients with severe secondary hyperparathyroidism. AB - Total parathyroidectomy with autotransplantation has been widely accepted as the appropriate treatment for patients with hyperparathyroidism due to chronic renal failure on long term hemodialysis. However, recurrence has been an enigma and therefore, the factors involved in the recurrence of hyperparathyroidism were studied in 128 patients followed for more than 2 years after surgical treatment. The preoperative serum parathyroid hormone (PTH) concentrations correlated with the total weights of the parathyroid glands. When the original autotransplanted glands were divided into two groups, being diffuse and nodular, the rate of recurrent hyperparathyroidism due to graft hyperfunction was significantly higher in the patients who received nodular glands (24%) than in those who received diffuse glands (8.4%) (P < 0.05). To investigate whether PTH synthetic activity is different in diffuse and nodular glands, the amount of PTH mRNA was studied by in situ hybridization. There was no significant difference in the amount of PTH mRNA in the cells from either diffuse or nodular glands. These data suggest that the recurrence of hyperparathyroidism is not due to enhanced PTH synthetic activity of autotransplant grafts but to the abnormal growth rate of the transplanted gland. PMID- 8467174 TI - Clinical and experimental studies on the role of platelet-activating factor (PAF) in the pathogenesis of septic DIC. AB - Various toxic factors induced by endotoxin (Et) are thought to be deeply involved in the pathogenesis of severe infections. In this study, particular attention was paid to the role of the platelet-activating factor (PAF) in these conditions, and clinical and experimental studies were conducted on the relationship between PAF and the changes observed in the general parameters after surgical infections. In the clinical study, changes in the PAF concentration in the blood of seven patients with disseminated intravascular coagulation (DIC), five of whom were septic and two non-septic, were monitored by gas/mas spectrometry. The mean PAF level in the septic DIC group tended to be higher than that in the non-septic DIC group. Moreover, in the septic DIC group, the relationship between the increase in the PAF level and platelet count was analyzed with the lapse of time and we surmised a negative correlation between these parameters. Experimentally, we also investigated the role of PAF in Et shock and the effect of an anti-PAF agent and protease inhibitor. The Et-induced fall in blood pressure was similarly prevented by both the anti-PAF agent and protease inhibitor. However, the decrease in the platelet count was more significantly inhibited by the anti-PAF agent than by the protease inhibitor, whereas the parameters of the blood coagulation/fibrinolysis system were more affected by the protease inhibitor than by the anti-PAF agent. PMID- 8467175 TI - K252a, a potent protein kinase inhibitor, improves endotoxic lethality and glucose dyshomeostasis. AB - To investigate whether the inhibition of protein kinases including protein kinase C can antagonize endotoxicosis, the in vivo effects of K252a, a potent inhibitor of protein kinases, on endotoxin-induced lethality and glucose dyshomeostasis were determined in conscious rats. Sprague-Dawley rats (260-340 g) were divided into the following four groups: Group DS, 2.5% dimethyl sulfoxide (DMSO), 6 ml/kg iv + 0.9% saline, 2 ml/kg iv; group KS, K252a in 2.5% DMSO, 4 mg/kg iv + 0.9% saline; group DE, 2.5% DMSO + endotoxin (E. coli), 15 mg/kg iv; and group KE, K252a in 2.5% DMSO + endotoxin. A quarter of DMSO or K252a solution was continuously infused over a 15 min period before a bolus injection of either saline or endotoxin. The remaining dose was administered over a 180 min period after saline or endotoxin. All animals in the DS and KS groups survived for 24 hrs. K252a significantly improved endotoxic lethality. It attenuated the initial hyperglycemia, and late hypoglycemia, hyperlactacidemia, and base deficit after endotoxin. However, K252a had no influence on the endotoxic alterations of blood pressure, PaCO2 or PaO2. These results suggest that the activations of protein kinases, particularly protein kinase C, are involved in the pathogenesis of lethal endotoxicosis and sepsis. PMID- 8467176 TI - Natural human IgG inhibits the production of tumor necrosis factor-alpha and interleukin-1 alpha through the Fc portion. AB - The overproduction of cytokines such as the tumor necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) may cause further deterioration in the already critical condition of patients with shock, sepsis, and acute inflammation. The effectiveness of infusion therapy of natural human IgG to such patients is suggested to depend partly upon the inhibition of the productivity of these cytokines. In this study, we investigated the modulation effects of IgG and its fragments on the production of TNF-alpha and IL-1 alpha, on human peripheral blood mononuclear cells (PBMC). The production of TNF-alpha and IL-1 alpha was found to be dose-dependently inhibited by IgG when stimulated by lipopolysaccharide (LPS), phytohemagglutinin (PHA), concanavalin A (Con A), and interleukin-2 (IL-2). However, no inhibition was seen when stimulated by phorbormyristate acetate (PMA). The F(ab')2 fragment showed enhancing effects on cytokine production by LPS, while the Fc fragment showed not as much inhibitory effect as whole intact IgG. IgG showed no direct cytotoxic effect on PBMC. These data suggest that natural human IgG inhibits TNF-alpha and IL-1 alpha production by PBMC through the Fc portion. The results of this study led us to conclude that whole intact IgG may be the best form of therapeutic delivery. PMID- 8467177 TI - Inflammatory pseudotumor of the spleen: report of a case. AB - A case of an inflammatory pseudotumor arising in the spleen of a 60-year-old Japanese male is described herein. This benign lesion is extremely rare, with only 12 cases, including our own, having been reported in the world literature. We preoperatively diagnosed the splenic tumor as a metastasis, due to the coexistance of advanced stage carcinoma in the sigmoid colon. However, after splenectomy, histopathological examination of the mass revealed an inflammatory process. Inflammatory pseudotumors often pose diagnostic difficulties because the clinical and radiologic findings are suggestive of malignancy. The clinical and pathological features of cases previously reported are reviewed following the presentation of this case. PMID- 8467178 TI - Small aorta syndrome. AB - A 47-year-old female with a 10-year history of bilateral intermittent claudication was diagnosed as having small aorta syndrome (SAS) and was successfully treated by an aorto-bifemoral bypass with aortic thrombendarterectomy. The infra-renal aorta was narrow, being 10 mm in diameter, with thrombotic occlusion of the terminal aorta and common iliac arteries. These findings were compatible with the features of SAS, however, there were few atherosclerotic changes in the abdominal wall and no evidence of any prediposing risk factors such as smoking or hyperlipidemia. Computed tomography, in addition to arteriography, seemed imperative for making the preoperative diagnosis. SAS is not uncommon as an established entity in Western Countries, but in Japan there have been few reports to date. The etiology, diagnosis, and management of this entity are reviewed following the presentation of this case. PMID- 8467179 TI - Juvenile gigantomastia: report of a case. AB - Juvenile gigantomastia in a 12-year-old girl was treated by a bilateral reduction mammoplasty with free transplantation of the areolae and nipples and the removal of 3,980 g of breast tissue. Regrowth of the residual breast tissue has been suppressed by the administration of tamoxifen, an antiestrogen drug, since the surgery. This case was positive for estrogen receptors (ER) by the dextran-coated charcoal method, while tissue staining for ER and estradiol resulted in a darker staining of the epithelial contents, especially of fibroadenoma-like nodules, using an immunocytochemical assay. It is thus suggested that the etiology of this disease might be related to a local hypersensitivity to estrogen. PMID- 8467180 TI - Primary neurilemoma of the thyroid gland: report of a case. AB - Neurilemoma, like other non-epithelial tumors, seldom occurs in the thyroid gland. A 57-year-old man was first referred to our hospital with an asymptomatic anterior neck tumor. A solid tumor was detected in the right lobe of the thyroid and an enucleation of the thyroid tumor was performed. The tumor was 35 x 33 x 33 mm in size, and diagnosed as Antoni A type neurilemoma. We were only able to find seven previously reported detailed cases of primary neurilemoma of the thyroid gland. A review of these cases, however, revealed that neurilemoma tends to develop in the right lobe of the thyroid gland. An operation is thus considered necessary and an enucleation of the tumor is appropriate. PMID- 8467181 TI - Heterotopic pancreas as a rare cause of gastrointestinal hemorrhage in the newborn: report of a case. AB - We report herein a female infant in whom a heterotopic pancreas in the stomach caused gastrointestinal hemorrhage during the newborn period. Endoscopy was essential for ruling out other causes of hemorrhage and to follow the patient until the time of elective surgery at 6 months of age. Heterotopic pancreas should be borne in mind as a rare cause of gastrointestinal hemorrhage in the newborn when an unexplained gastrointestinal hemorrhage continues, and the lesion was discussed in relation to our experience of upper gastrointestinal endoscopies and a review of the literature. PMID- 8467182 TI - Hemangioma of the upper arm associated with massive hemorrhage in a neonate. AB - A rare case of an ulcerated hemangioma of the upper arm in a neonate is described herein. Resection of the huge hemangioma, which occupied the axilla and extended down the entire length of the upper arm, was necessary due to massive hemorrhage from the ulcer and progressive heart failure caused by the arteriovenous fistula in the hemangioma. After complete resection of the hemangioma, extensive defects of the skin and subcutaneous tissue were replaced by a skin flap closure technique which involved considerable difficulty. However, the arm gradually recovered its size and function with good wound healing. The present case illustrates that rapid surgical intervention may be required to prevent clinical deterioration in such cases. PMID- 8467183 TI - A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats. AB - Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E1 (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 micrograms/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 micrograms/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 micrograms/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 micrograms/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response. PMID- 8467184 TI - An experimental study on intestinal vascular lesions: a comparison between the effects of arterial and venous occlusion in the acute phase. AB - In order to clarify what early ischemic changes are produced by venous interruption in the intestine, intestinal vascular lesions caused by peripheral venous ligation were compared with those caused by arterial ligation in rabbits. With less than 30 min ligation, there were only 4 specimens from a total 13 without injury following venous ligation, whereas there were 7 from a total 11 without injury following arterial ligation. After 30 min venous ligation, both the mucosal and submucosal layers of all 10 specimens were affected, while following arterial ligation, 3 of the 11 specimens showed no histological changes. Moreover, in 3 of the remaining 8 specimens from the latter group, the injury was confined to within the mucosal layer. Thus, in cases of venous interruption, intestinal injury might be evoked earlier with more severe damage than in cases of arterial interruption. PMID- 8467185 TI - Nurses remain ignorant over HIV/AIDS. PMID- 8467186 TI - Practical tips for writers. PMID- 8467187 TI - Blood glucose monitoring in the intensive care unit. AB - Patients in intensive care units may have high blood glucose levels for a variety of reasons. Careful control of blood glucose has a number of advantages. Nurses need to be trained in the use of blood glucose meters to obtain accurate results. PMID- 8467188 TI - Nursing management of irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) affects up to 25% of the population and accounts for about 40% of patients referred to consultant gastroenterologists (Nagvi and Prout, 1983). Despite this, much of the medical and dietary research is conflicting and inconclusive. This article discusses the variety of symptoms and treatments associated with IBS and the nursing management of the condition. PMID- 8467189 TI - Mouth care and the hospitalized patient. AB - Despite its importance, there still appears to be some confusion among nurses regarding mouth care and the tools that should be used. This article reviews the literature and suggests the best possible approach. PMID- 8467190 TI - Intuition and expert clinical practice in nursing. AB - The quest for the essence of nursing in the UK continues unabated. Similarly, the concept of what constitutes expert clinical practice and the problem of how it can be achieved are topical issues. This article considers the notion of a developmental process in nursing and the concept of reflective practice, and examines the idea of intuition as a key component in the functioning of the expert nurse. PMID- 8467191 TI - The Bland truth: 1. PMID- 8467192 TI - Nurses' role in encouraging organ donation. AB - There is currently a shortage of transplantable organs, mainly because the relatives of potential organ donors dying in hospital are not routinely offered the choice of donating their loved one's organs. Nurses are ideally placed to perform this function, and those who have had the courage to approach relatives of potential organ donors have found it a worthwhile experience. PMID- 8467193 TI - Ethical implications of first aid. AB - Nurses have a moral duty to act when faced with emergency situations. Fear of legal recourse is no excuse for failing to provide first-aid care. This article considers the ethical implications for the nurse, midwife and health visitor at the scene of an accident. PMID- 8467194 TI - The G grade ward sister: clinical expert and ward manager. AB - The role of ward sister is changing and increasingly veering towards a middle management role. This article discusses the qualities and skills needed by a ward sister if she is to maintain her traditional role as clinical expert while also fulfilling her new role as ward manager. PMID- 8467195 TI - Influence of chronic alcohol consumption on the development of altered hepatocellular foci in rats. AB - The effect of chronic alcohol consumption on the development of altered hepatocellular foci was examined in 150 male Slc:Wistar rats fed an ethanol solution (0, 5 or 20%, w/v) ad libitum instead of drinking water. In the 120th week of the treatment period, the liver was examined histopathologically. There was no significant difference in the incidence, number and volume fractions of altered hepatocellular foci between the 0% and the 5% ethanol groups. In the 20% ethanol group, the incidence of altered hepatocellular foci was significantly higher than in the 0% ethanol group, and the number and the volume fraction of altered hepatocellular foci were significantly greater than in the 0% and the 5% ethanol groups. These results indicate that chronic consumption of a large amount of alcohol promotes the development of altered hepatocellular foci. However, there was no statistically significant difference in the incidence of benign liver cell tumours and hepatocellular carcinoma among the three groups. PMID- 8467196 TI - Experimental pulmonary hypertension induced by constriction of the pulmonary arteries resulting in rupture or extraordinary dilatation of the right ventricle after administration of a little amount of Na2EDTA. AB - Our earlier studies on the hypocalcemic condition have focused on the histological distortion of the organ structure with the removal of the calcium ion from the molecular structure of acid mucopolysaccharides (AMPs); resulting in the sol-gel diversion of the matrix. Bivalent cationic materials including calcium are related not only to function but also to structural alteration of the living organism (Yamaguchi et al. 1978, 1981, 1982, 1985, 1991). The ionic shift from the structural phase to the functional phase induced a number of morphological distortions of the various organs. In the present paper, starting our research from a different experimental viewpoint, we decreased the Na2EDTA dose used to prevent the conventional typical tetanic shock which sometimes results in animal death. We expected this decreased dose to induce mild constriction of muscle cells. In our experiment, administration of a small amount of Na2EDTA intraperitoneally provoked animal death after 10 days to two weeks over a two-month period. In the initial phase of 10 days to two weeks, rupture of the right ventricular wall along the septum occurred at an anterior angle with moderate right ventricular dilatation and a remarkably thin ventricular wall. Characteristic of these cases was elastosis between the medial smooth muscle cells of the main pulmonary arteries accompanied by a severe degree of constriction. On the other hand, demonstrated in the delayed cases of between more than two weeks to two months there was severe dilatation of the right ventricular lumina with paper-like thinness of the wall. In these cases, the main pulmonary arteries showed rather slight constriction with scarce elastosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467197 TI - Transplantability and MHC antigen expression of tumor mast cells. AB - A cloned cell line was established from tumor cells spontaneously developed in a coculture of an autoreactive T cell line (1/+ T1) and 30 Gy-irradiated MRL/+ spleen cells with Con A supernatants. Morphological studies and studies of histamine content and modes of histamine release after stimulation with compound 48/80 revealed that the cell line (MRL-MC3) had mast cell characteristics. MRL MC3 was transplantable not only to MRL/+, MRL/lpr and AKR/J (H-2k) mice but also to BALB/c and (BALB/c x DBA/2) F1 (H-2d) mice, although the allogeneic mice survived twice as long as syngeneic mice after i.v. injection. In addition, after i.v. injection, the mast cells infiltrated the livers and spleens of syngeneic (MRL/+) mice, however the lymph nodes around the mesenterium to the parapylorus in allogeneic (BALB/c) mice. A mast cell line (BALB-MC) was also established from a lymph node of MRL-MC3-injected BALB/c mice. Cell surface marker analyses revealed clear differences between the BALB-MC and the original MRL-MC3, which was positive for the expression of MHC class I antigens (K, D), I-E antigen and c abl-encoded (anti-pEX-2 antibody-reactive) proteins, but not for I-A on the cell surface. In contrast, BALB-MC showed positive only for the MHC class I antigens (K, D) on the surface, and also positive for anti-pEX-2 antibody-reactive cytoplasmic proteins, as seen in MRL-MC3. Mast cells obtained from MRL-MC3 injected MRL/+ mice showed the same staining pattern as MRL-MC3. BALB-MC induced shorter survival times (approximately half) in both MRL/+ and BALB/c mice than MRL-MC3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467198 TI - Enhanced effect of chronic stress on pregnancy outcome in Uje:WIST rats by prenatal treatment with lithium. AB - Female Uje:WIST rats were exposed to lithium (20 mmol LiCl/l drinking water, lithium levels about 1 mmol/l serum) for at least three weeks before mating and continuously up to the end of gestation. Female F1-offspring were raised without further treatment and mated at an age of 90-120 days with untreated males. The effect of chronic restraint stress during gestation on pregnancy outcome was estimated. Moderate changes (higher frequency of prolonged gestation, decreased body mass of the newborn pups) resembled those which were induced by considerably longer stress exposure (extended to the premating period) of prenatally untreated female Uje:WIST rats. An enhanced stress sensitivity following prenatal lithium treatment is discussed. PMID- 8467199 TI - Stability of pituitary weight after multiple reproductive cycles. PMID- 8467200 TI - The effects of adriamycin on dental proteins formation and mineralization in vitro. AB - Second maxillary molars of 4-5 days old golden hamsters were exposed for 2 h in vitro to 1 mg/L adriamycin, rinsed and subsequently cultured up to 7 days without the drug. At days 3, 5 or 7 of culture the synthesis of extracellular tooth matrices and their mineralization were examined by measuring the incorporation of 3H-proline and the uptake of 45Ca and 32PO4 by the explants during a 24 h pulse labeling. Compared with unexposed control explants, exposure to adriamycin for the first 2 h of culture had no effect on total biosynthesis of proline containing matrix proteins. However, at days 3 and 5 of culture it increased the quantity of water-soluble enamel matrix proteins (amelogenins). Adriamycin also strongly reduced the amount of organically-bound 32P-activity in a fraction extractable with guanidine-HC1-EDTA only, allegedly containing a mixture of mineral-associated proteins from both enamel and dentin. Since this decrease of 32P-activity coincided with the formation of osteodentin in the pulp as shown previously in histological and electron microscopical studies, it was speculated that osteodentin matrix may not contain the highly phosphorylated, dentin specific phosphoproteins (DPP). Adriamycin also affected the uptake of 45Ca and 32PO4. At day 3 these values were slightly higher than control values but lower at days 5 and 7. It therefore appears that a 2 h exposure to adriamycin in concentrations as low as 1 mg/L causes an acceleration of secretory amelogenesis by tooth germs in vitro. It also induces pulp cells to form osteodentin. PMID- 8467201 TI - Determination of lead in paired samples of blood and synovial fluid of bovines. AB - Exposure of synovial fluid to lead allows the entrance of this metal into the systemic circulation. In this study we report lead concentrations measured in bovine paired samples of synovial fluid and whole blood withdrawn from the coxo femoral joints and jugular vein, respectively. Lead was determined by atomic absorption spectrophotometry. This study provides the "normal" values for lead in synovial fluid 12.15 +/- 5.41 and blood 3.54 +/- 1.31 micrograms% (mean +/- SD). The data distribution fits the GAUSSIAN curve (p < 0.02). The difference of concentration between synovial fluid and blood can not be explained only in terms of the solubility of lead in both fluids; other factors must be considered. PMID- 8467202 TI - Ossification of the vertebral column in the offspring of rats exposed to alcohol, acetaldehyde and caffeine. AB - The embryopathic effects of alcohol have been widely studied in humans and laboratory animals. However, the role of risk factors remains largely unknown. Whereas skeletal abnormalities are often present in the offspring of alcoholic mothers, these have not been fully documented. This report is concerned specifically with the development of the vertebral column in rats exposed in utero to ethanol, its primary metabolite acetaldehyde, and caffeine. Our results indicate a possible causal association between alcohol abuse and ossification anomalies of the vertebral column. Maternal treatment with caffeine accelerated ossification in the sacro-caudal vertebrae. Caffeine combined with ethanol only moderately affected the development of the centra and arches. PMID- 8467203 TI - Lack of tumorigenic activity of 1,1-dimethylhydrazine in Syrian golden hamsters treated by subcutaneous injection. AB - Syrian golden hamsters were treated throughout their lifespan by weekly subcutaneous injections of 1,1-dimethylhydrazine (1,1-DMH) at doses of 0, 8, 17 and 35 mg/kg body weight. In contrast to our previous study using European hamsters, no treatment-related tumors occurred in this study. PMID- 8467204 TI - Approaches to epilepsy surgery. AB - The different approaches to epilepsy surgery are discussed. Despite considerable differences in rationale, patients, and operative technique, there are apparently similar outcomes. There are no controlled studies available comparing these different techniques. PMID- 8467205 TI - History of focal epilepsy and criteria for medical intractability. AB - In this article the issues surrounding the definition of medical intractability have been discussed. Acceptable seizure control is primarily defined by the patient. If in a given living situation the number of seizures a patient is having (even if quite small) is interfering to the point that they are willing to consider epilepsy surgery as a treatment modality, there is unacceptable seizure control. More difficult is the definition of what constitutes an adequate trial of anti-epilepsy drugs. A consensus is that patients should have had at least trials to toxicity, toxicity as defined by patients' signs or symptoms (and not by drug levels), of at least two major anti-epilepsy drugs. Trials of combined therapy are not necessary. The natural history of these patients is such that if they have not been controlled with adequate trials of drugs within 2 years, they are unlikely (< 10% probability) to enter a long-term permanent remission of their seizures. These patients are medically intractable. PMID- 8467206 TI - Imaging criteria to identify the epileptic focus. Magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography scanning, and single photon emission computed tomography. AB - The use of MRI, MRSI, PET, and SPECT scanning for preoperative evaluation of patients with epilepsy is reviewed. MRI provides the best anatomic detail and contains prognostic information. PET provides useful information in some patients for whom MRI findings are absent or contradictory. Interictal SPECT scanning lacks sufficient specificity to be of use in the preoperative evaluation of refractory patients, whereas ictal SPECT appears to be useful in temporal and extratemporal lobe epilepsy. The new technique of MRSI is described. PMID- 8467207 TI - Preoperative criteria for identifying eloquent brain. Intracarotid amytal for language and memory testing. AB - The intracarotid Amytal procedure is a useful method for preoperative assessment of language dominance. It is also helpful for assuring that the contralateral hemisphere can sustain adequate memory function following temporal lobectomy. The methods of language and memory testing using intracarotid Amytal procedure are discussed. PMID- 8467208 TI - Intraoperative and extraoperative identification of eloquent brain using stimulation mapping. AB - Intraoperative and extraoperative stimulation mapping provides a reliable mechanism for identification of functional cortex in patients who are to undergo resective surgery for epilepsy. The techniques available for performing stimulation mapping are discussed. PMID- 8467209 TI - Surgical anatomy of the temporal lobe. AB - The complex functional and anatomic relationships between the structures in and around the temporal lobe are central to the problem of intractable partial complex seizures. Resecting those areas that are responsible for seizures and protecting those that are essential for the normal functioning of the patient are the fundamental tasks of the epilepsy surgeon. A thorough understanding of the structural and functional anatomy of this region is essential to achieve these goals. PMID- 8467210 TI - Anatomic temporal lobe resections for temporal lobe epilepsy. AB - Temporal lobe epilepsy is not a single clinicopathologic entity but a group of syndromes requiring different surgical solutions. Anatomic resections planned for the treatment of these syndromes are aimed at pathologic substrates minimizing ablation of normal tissue. Most of these procedures involve mesial and lateral temporal resections. The syndrome of mesial temporal sclerosis should be treated with resection aimed at hippocampus and the PHG, including entorhinal cortex, and at part of the amygdala. Improvement in diagnostic methods and refinement of anatomic surgical procedures that maximize resection of hippocampus resulted in excellent outcome in the treatment of patients with this syndrome. Mass lesions in patients with intractable seizures should be resected with some surrounding margins, but additional clinical studies will be required to determine the role of anatomic resections, including hippocampectomy, in the treatment of these patients. Extrahippocampal temporal lobe epilepsy is the most difficult to evaluate and treat. Tailored individualized resections based on acute or chronic EEG recordings may be required until and if discrete anatomically based syndromes can be identified in this patient population. PMID- 8467211 TI - Surgery and results of selective amygdala-hippocampectomy in one hundred patients with nonlesional limbic epilepsy. PMID- 8467212 TI - Temporal lobectomy that spares the amygdala for temporal lobe epilepsy. AB - Rationale, surgical techniques, and results in 70 patients with complex partial seizures who underwent temporal lobectomy with sparing of the amygdala are discussed. Removal of entorhinal cortex may be the common denominator that explains the similar results obtained with different types of temporal lobectomies for epilepsy. PMID- 8467213 TI - The tailored temporal lobectomy. AB - The indications, rationale, operative technique, risks, and outcome from the tailored temporal lobectomy are reviewed. The tailored lobectomy allows intraoperative identification of both electrically active cortex and functionally essential cortex, thus permitting maximal resection of epileptic regions without damage to Rolandic cortex or essential language cortex. This allows surgical strategy to be planned on the basis of preoperative interictal scalp electroencephalography recordings, thus lowering hospital costs and avoiding risk of implanting intracranial electrodes. PMID- 8467214 TI - Extratemporal resective surgery for epilepsy. AB - Extratemporal resections were the most common early operations for epilepsy. This area is in need of further investigations, however, as relatively little progress has been made in management of these cases. The surveys from the Palm Desert Conferences on extratemporal resections with at least 1 year follow-up indicate that of the 825 patients operated between 1949 and 1984, 43.2% were said to be seizure free, 27.8% improved, and 29.1% not improved. Between 1986 and 1990, 768 patients underwent extratemporal resections, with 44.5% seizure free, 35.7% improved, and 19.8% not improved. Thus, there has not been a major improvement in the seizure-free outcomes, although more patients are undergoing surgical treatment and there are increases in the "improved" category. Moreover, these results are worse than those for temporal resections reported by the same surveys. As is apparent from this article, extratemporal epilepsies are very heterogeneous. The techniques of electrophysiology that have been so successful with temporal lobe epilepsy seem to be less so with many extratemporal epilepsies, however, suggesting that improved outcomes for those conditions especially may depend on new techniques, such as those based on imaging. PMID- 8467215 TI - The role of callosal section in surgical treatment of epilepsies. AB - Using current microsurgical technique, the procedures of both partial and complete corpus callosum section may be performed with minimal morbidity and with full assurance of completeness of callosal fiber division. Between 65% and 80% of patients have had significant improvement in terms of generalized seizure control. These results are similar to those observed at a number of other epilepsy centers now performing this surgery, and the benefit is long lasting. The neuropsychologic effects of callosal division have now been fairly well characterized. Although demonstrable in all patients, these rarely have been problematic and in nearly all instances have been outweighed by the benefit in terms of seizure control. PMID- 8467216 TI - Surgery for epilepsy. Special pediatric considerations. AB - Children with epilepsy require special consideration because the nature of their seizures is different from those in adults, the effects of intractable epilepsy may be more serious in children, and younger children may have greater potential for recovery than adults. This article reviews the unique problems and approaches to resective surgery for pediatric epilepsy. PMID- 8467217 TI - Complications of epilepsy surgery. AB - In the treatment of patients with medically intractable epilepsy, neurosurgeons are involved in the application of invasive monitoring procedures and definitive surgical therapies, including resective and disconnection surgery. Each alternative intervention carries with it a unique set of potential adverse outcomes or complications, which provides the principal focus of this article. PMID- 8467218 TI - Surgical resection of epileptogenic cortex associated with structural lesions. AB - In this article we have reviewed the available data for postsurgical seizure control in patients with both structural lesions and seizures. There is evidence that simple excision alone will control seizures in some patients, whereas others require, in addition, seizure surgery with resection of epileptogenic cortex. When available studies are reviewed and submitted to meta-analysis, however, we have found that more patients are seizure free at 2-year follow-up after seizure surgery than after simple excision. Seizure control is one of the many factors that influence the choice of surgical approach. Therefore, we do not recommend that all patients with structural lesions and seizures disorders undergo seizure surgery. Rather, for those patients with a structural lesion in whom seizures are medically intractable, our review supports excision of the structural lesion as well as resection of the epileptogenic cortex to provide the patient with the best opportunity of seizure control. PMID- 8467219 TI - Seizure outcome in patients undergoing temporal lobe resections for epilepsy. AB - This article reviews the results of surgical treatment of temporal lobe epilepsy based on retrospective reviews: more recent surveys from 91 centers on the outcomes from the surgical treatment of epilepsy and preliminary data from the authors' institution's 5-year retrospective review of nearly 100 surgical patients matched to medically treated epileptics. Surgical outcomes from resections in other areas, including extratemporal resections, and the efficacy of lesionectomy versus epilepsy surgery for structural lesions are detailed elsewhere in this issue. PMID- 8467220 TI - Resection surgery for epilepsy. Outcome and quality of life. AB - Psychosocial problems frequently are more difficult to manage than the seizures. Quality of life investigations are important in identifying psychosocial issues that impede the benefits of improved or complete seizure control. Three categories of quality of life assessment are discussed: professional observation and ratings, psychometric assessment, and community-based measures of adaptive ability. PMID- 8467221 TI - Identification of a methyl jasmonate-responsive domain in the soybean vspB promoter. AB - Soybean vspB encodes a highly expressed vegetative storage protein-acid phosphatase. In soybean, vspB expression is stimulated by methyl jasmonate (MeJA) and sugars. The vspB promoter was studied by transforming tobacco with fusions of 5' noncoding vspB DNA and the gene encoding beta-glucuronidase (GUS). Constructs containing 833 bp of vspB 5' DNA showed high expression of GUS in stems, leaf veins and trichomes, sepals, and pollen. Sucrose (0.2 M) and MeJA (10(-5) M) increased gene expression when applied to leaf tissue. Deletion of the region 787 to -520 with respect to the transcription initiation site rendered the vspB promoter noninducible by MeJA but still sucrose responsive. This result indicates that DNA elements capable of modulating vspB by MeJA can be separated from carbon response elements. Further 5' end deletion from -520 to -403 or 3' end deletion from -165 to -289 removed DNA sequences involved in carbon modulation of gene expression. A DNA domain that mediates the MeJA response was further localized to a 50-bp region between -535 and -585. This domain when fused to a cauliflower mosaic virus (CaMV) 35S truncated (-88) promoter makes the CaMV promoter responsive to MeJA. The MeJA-responsive domain contains a G-box motif (CACGTG) and a C-rich sequence. A similar 50-bp DNA region is present in the putative promoter of vspA. Related sequences are located in a wound- and MeJA-responsive domain of the proteinase inhibitor II gene and a UV-responsive promoter domain of chs, the gene encoding chalcone synthase that is also responsive to MeJA. PMID- 8467222 TI - Developmental expression and localization of petunia glycine-rich protein 1. AB - An anti-petunia glycine-rich protein 1 (ptGRP1) antibody was used for biotin streptavidin-alkaline phosphatase localization of this protein. In petunia stem and leaves grown under different light conditions, these studies revealed a complex pattern of cell localization for this protein. Levels of ptGRP1 were shown to decrease with developmental age of the tissue, appearing to correlate directly with expansive growth and inversely with lignification. Significantly, plants grown under low light (approximately 32 mumol m-2 sec-1 at noon) showed at least an eightfold increased level of ptGRP1 protein throughout ptGRP1's expression period when compared to plants grown under higher light (approximately 80 mumol m-2 sec-1 at noon). Evidence also indicated that for one cell type in which ptGRP1 is localized, this protein is imported rather than synthesized. In addition, confocal microscopy studies suggested that ptGRP1 is deposited at the cell wall/membrane interface rather than within the cell wall. PMID- 8467223 TI - The patterns of gene expression in the tomato shoot apical meristem. AB - In this paper, we describe the synthesis of a cDNA library from the vegetative shoot apical meristem and the analysis of clones selected from it. Using in situ hybridization, we characterized the patterns of expression of these genes in the tomato shoot apical meristem, as well as the patterns obtained from other sources. The results from the analysis of 15 cDNAs indicated the following six main patterns of gene expression in the shoot apical meristem: overall expression, zero expression, expression limited to the epidermis, expression excluded from the epidermis, punctate expression, and expression elevated in the flanks of the meristem. The patterns observed and the nature and number of the genes showing these patterns necessitate a reinterpretation of the models of meristem structure and function. In particular, the data suggest a compartmentation within the shoot apical meristem based on the spatial expression of particular subsets of genes. This paper also reports on the specific and precise criteria essential for the correct identification of meristem-specific gene expression. The data give new insight into the molecular organization of the shoot apical meristem and provide the framework for a detailed dissection of the factors controlling this organization. PMID- 8467224 TI - Expression of an Atriplex nummularia gene encoding a protein homologous to the bacterial molecular chaperone DnaJ. AB - DnaJ is a 36-kD heat shock protein that functions together with Dnak (Hsp70) as a molecular chaperone in Escherichia coli. We have obtained a cDNA clone from the higher plant Atriplex nummularia that encodes a 46.6-kD polypeptide (ANJ1) with an overall 35.2% amino acid sequence identity with the E. coli DnaJ. ANJ1 has 43.4% overall sequence identity with the Saccharomyces cerevisiae cytoplasmic DnaJ homolog YDJ1/MAS5. Complementation of the yeast mas5 mutation indicated that ANJ1 is a functional homolog of YDJ1/MAS5. The presence of other DnaJ homologs in A. nummularia was demonstrated by the detection of proteins that are antigenically related to the yeast mitochondrial DnaJ homolog SCJ1 and the yeast DnaJ-related protein Sec63. Expression of the ANJ1 gene was compared with that of an A. nummularia Hsp70 gene. Expression of both ANJ1 and Hsp70 transcripts was coordinately induced by heat shock. However, noncoordinate accumulation of ANJ1 and Hsp70 mRNAs occurred during the cell growth cycle and in response to NaCl stress. PMID- 8467225 TI - The enigma of slow viruses. Facts and artefacts. PMID- 8467226 TI - Bone marrow transplantation in sickle cell anaemia. AB - Sickle cell anaemia is a hereditary disorder commonly seen in the black population, due to a point mutation in the beta globin gene. The sickle mutation is responsible for an increased rigidity and adherence of the red blood cell leading to haemolytic anaemia and vaso-occlusive episodes. Symptoms include dactylitis, painful crisis, splenic sequestration and the development of multi organ damage and failure. The progressive loss of splenic function increases the risk of infections. The morbidity and mortality can be reduced by the maintenance of an adequate nutrition, the prevention of infection and the treatment of complications. In some patients severely affected, a chronic transfusion program has to be instigated to maintain a level of haemoglobin S below 50%. New therapeutic strategies include the use of hydroxyurea and maybe, in the future, butyrates to increase the level of foetal haemoglobin. Further studies are needed to evaluate the benefits of such therapies. Bone marrow transplantation represents an attractive therapeutic tool and its role in other haemoglobinopathies like thalassaemia is now well demonstrated. As far as sickle anaemia is concerned, the first report concerned a child with acute myeloblastic leukaemia. The patient is now cured of both the sickle cell anaemia and the leukemia. Since April 1986, 21 patients underwent an allogeneic bone marrow transplantation for sickle cell anaemia in our department. 20 patients became asymptomatic and have an electrophoretic pattern of the haemoglobin similar to that of the donor. One patient died of bone marrow transplantation related complications. PMID- 8467227 TI - Karyotypic analysis in primary myelodysplastic syndromes. AB - Cytogenetics has provided new insights into the biology and pathogenesis of myelodysplastic syndromes. In patients with refractory anemia, it has provided proof of clonality and has helped differentiate chronic myelomonocytic leukemia from chronic myeloid leukemia. As a prognostic tool, cytogenetics has been predictive of duration of survival and leukemic transformation. However, its role as an independent prognostic factor compared with recent prognostic scoring systems remains to be determined. New techniques such as fluorescent in situ hybridization using chromosome-specific DNA probes may expand the usefulness of cytogenetics. The prognostic impact of cytogenetics may not be fully realized until more effective treatments become available. PMID- 8467228 TI - Multiple myeloma: the biology of malignant plasma cells. AB - Multiple myeloma remains a difficult disorder to treat and cures are virtually unknown. Most modalities of treatment have been tried on an empirical basis, and a greater understanding of the nature of myeloma progenitors may lead to more specific therapies. In the past few years interest in the biology of myeloma plasma cells has increased and the current state of knowledge is summarised in this review. Myeloma clonogenic, or colony, assays have been attempted by many groups. Despite this, no direct equivalent is available of the CFU-GM assay for granulocyte-macrophage progenitors in normal marrow. No published methods have been exported widely to other laboratories. Recently, myeloma plasma cells were found to express a wide range of adhesion molecules permitting cell to cell and cell to stroma interactions. This finding may explain the difficulty of myeloma colony assays, since adhesive clumping must be prevented. The observation that interleukin (IL)-6 can stimulate myeloma plasma cells led to further work with other cytokines such as IL-3 and GM-CSF. The precise role of IL-6 in the usual case of bone marrow myeloma remains unclear however. PMID- 8467229 TI - Biology and treatment of multiple myeloma. AB - The uniformly fatal plasma cell malignancy, multiple myeloma (MM), currently represents 10-15% of hematologic neoplasms in the USA and has been steadily increasing in incidence for several decades. Therapeutic alternatives have lagged significantly behind insights into the biology and pathogenesis of this entity. Traditionally felt to be a neoplasm of fully differentiated plasma cells, evidence has been mounting that the self renewing population consist of cells derived from a much earlier compartment; perhaps prior to B-cell lineage commitment or even at the level of an earlier 'stem cell'. Bcl-2 protein overexpression has been almost uniformly seen in both clinical myeloma specimens as well as in myeloma cell lines. The failure to consistently identify the t(14;18) translocation, normally found in follicular lymphomas and characteristically associated with overexpression of bcl-2, implies a unique mechanism in MM. A number of cytokines, including TNF alpha, IL-1 and IL-6 have been found to play a central role not only in the biology of the malignant clone but also in the bony and other systemic manifestations of this disease. Since both IL-6 and bcl-2 protein have been shown to prevent programmed cell death, this may be the unifying event in MM. Standard therapy for MM has been an alkylating agent and corticosteroid. Combination chemotherapy provides more prompt palliation but no clear survival advantage. In advanced stages, adriamycin may offer some survival advantage. High dose chemotherapy with or without stem cell support offers a potentially curative therapeutic approach. New interventions directed at the complex cytokine networks pertinent to the pathogenesis of MM are an exciting new area of investigation. Identification of new prognostic parameters as well as new active agents remains the central theme in clinical myeloma research. PMID- 8467230 TI - Treatment of early stage Hodgkin's disease. AB - Current trends in the treatment of patients with Stages I and II Hodgkin's disease are discussed in this review. Recommendations for staging procedures and the updated staging classification are described. Long-term results with extended field radiation therapy overall and in subgroups of patients are detailed. As follow-up and numbers of patients treated with extended field radiation therapy have accrued, prognostic factors, predictive of outcome, have emerged. The evolution of combined modality treatment with chemotherapy and radiation therapy and, more recently, chemotherapy alone for early stage patients is reviewed. Discussion is made of recent programs in various centers to reduce toxicity while maintaining good results. Long-term potential toxicities are described, and recommendations are made for long-term follow-up monitoring. PMID- 8467231 TI - Bone marrow transplant for sickle cell disease--the dilemma. AB - Sickle cell disease is the family of clinically significant haemoglobin disorders which have in common the inheritance of the sickle beta haemoglobin chain gene. The homozygous SS condition, also known as sickle cell anaemia, can present a varied clinical picture from asymptomatic through to frequent painful vaso occlusive crises and even death as a result of complications of the disease. S beta zero thalassaemia and the rate haemoglobin SD disease present a similar picture to SS, while S beta plus thalassaemia and haemoglobin SC disease generally have milder clinical features than SS and present somewhat later in life. The present debate about bone marrow transplant (BMT) for sickle cell disease, among both physicians and community, relates to SS patients, definition and markers of disease severity, the effect of BMT on sickle related organ damage, the efficacy of BMT for SS, and its complications, both early and long term. PMID- 8467232 TI - Hepatic veno-occlusive disease after bone marrow transplant. AB - Hepatic veno-occlusive disease (VOD) is a non-thrombotic obliteration of the lumina of small intrahepatic veins. VOD has been reported after exposure to a wide variety of pathogens. It has been suggested that the chemoradiotherapy used as the conditioning regimen for bone marrow transplant (BMT) is now the main cause of this disease. However, the pathogenesis of VOD after BMT is probably multifactorial. Endothelial injury of sinusoids and small hepatic veins is considered to be the initial event in genesis of VOD. This injury is followed by deposition of fibrin-related aggregates in the subendothelial zone. These aggregates, and the intramural entrapment of fluid and cellular debris, occlude progressively the hepatic venous outflow and generate a postsinusoidal intrahepatic hypertension. Clinically, VOD is characterized by jaundice, weight gain, ascites, painful hepatomegaly and platelet refractoriness developing early post transplant, although other posttransplant liver disturbances can produce a similar syndrome. VOD diagnosis is usually established by applying the clinical criteria proposed by the Seattle and Baltimore groups. When clinical diagnosis of VOD is uncertain, a transjugular liver study including a transvenous biopsy and measurement of the gradient between wedged and free hepatic venous pressure, is recommended in order to establish an accurate diagnosis. According to the literature data, the incidence of VOD ranges from 0 to 70% and its mortality from 20 to 50%. This very wide range is attributable to the different incidence of risk factors in the different series and to the differences in applying the diagnostic criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467233 TI - Platelet alpha-granules. AB - Platelets contain a vast number of biologically active molecules within cytoplasmic granules which are classified according to their respective distinct ultrastructures, densities and content. The alpha-granule is a unique secretory organelle in that it exhibits further compartmentalization and acquires its protein content via two distinct mechanisms: (1) biosynthesis predominantly at the megakaryocyte (MK) level (with some vestigial platelet synthesis) (e.g. platelet factor 4) and (2) endocytosis and pinocytosis at both the MK and circulating platelet levels (e.g. fibrinogen (Fg) and IgG). The currently known list of alpha-granular proteins continues to enlarge and includes many adhesive proteins (e.g. Fg, von Willebrand factor (vWf) and thrombospodin (TSP)), plasma proteins (e.g. IgG and albumin), cellular mitogens (e.g. platelet derived growth factor and TGF beta), coagulation factors (e.g. factor V) and protease inhibitors (e.g. alpha 2-macroglobulin and alpha 2-antiplasmin). More recently the inner lining of the alpha-granule unit membrane has been demonstrated to contain a number of physiologically important receptors including glycoprotein IIb/IIIa (alpha IIb beta 3) and P-selectin. The alpha-granules originate from small precursor granules which can be observed budding from the trans-Golgi network within the platelet precursor cell the MK. During MK maturation the alpha granules become very prominent and are ultimately packaged into platelets during thrombopoiesis. The alpha-granular contents are destined for release during platelet activation at sites of vessel wall injury and thus play an important role in haemostasis, inflammation, ultimate wound repair and in the pathogenesis of atherosclerosis. PMID- 8467234 TI - The role of apoptosis (programmed cell death) in haemopoiesis and the immune system. AB - Apoptosis, or programmed cell death, is a series of controlled sequential events resulting in the demise of cells without invoking an inflammatory response. It is a naturally occurring process which maintains a cellular balance during both animal development and in the mature adult. Although first described 20 years ago, there is now renewed interest in this phenomenon, particularly in the light of our greater understanding of cellular signalling pathways and their genetic control. This is especially pertinent to haemopoiesis and the overall maintenance of a functional immune system. This review broadly covers the biochemical events of apoptosis and the recognition of apoptotic cells by phagocytes. Reference is made to the selective development of T- and B-cells and to the control of inflammation. Molecular events in apoptosis are also discussed with special reference to aberrant bcl-2 gene expression in follicular B-cell lymphoma and the role of other death genes in the control of apoptosis. PMID- 8467236 TI - Detection of mRNA encoding an antibacterial-metalloprotein (MPII) by in situ hybridization with a cDNA probe generated by polymerase chain reaction in the worm Nereis diversicolor. AB - Based on partial amino acid sequence of an antibacterial-metalloprotein (MPII) consisting of a N-terminal fragment (1-33th) and an 43 amino acids long internal fragment, two oligonucleotides primers were synthesized and used to generate a cDNA fragment by the PCR method. The specificity of the PCR synthesized 220 bp fragment was verified by hybrid-arrest translation and sequencing. In situ hybridization performed with this cDNA fragment on Nereis diversicolor whole body defined two specific sites of recognition: a cluster of cells floating in the coelom and two types of muscles (perineural and oblique). Finally, the chronological expression of the MPII was postulated. PMID- 8467235 TI - Timely and topologically defined protein synthesis in the peri-implanting mouse endometrium revealed by light and electron microscopic radioautography. AB - Many efforts have been made to correlate the morphological and biochemical evidences with changes on physiological state of the uterus during activation of the implantation window. However, the exact mechanism involved in such a phenomenon remains to be determined. The present experiment used the radioautographic approach to determine whether, chronological and/or topological variations of proteins synthesis occur in the peri-implanting endometrium. Pregnant mice submitted to ovariectomy, received exogenous supply of nidatory estradiol. After 0 to 18 hrs. of time-lapsed estradiol effects, each animal received intraperitoneally, 1 hr. pulse 3H-leucine. The uterine fragments embedded in epoxy resin, were processed for light and electron microscope radioautography. The pattern of 3H-leucine incorporation in the luminal epithelium varied according to their relation with the blastocyst present in the uterine lumen. The highest incorporation ratio was seen in the epithelium just around the conceptus 6 hrs. after estradiol treatment, while in the cells localized at interimplantation site no peak of incorporation was seen. At ultrastructural level, cell organelles involved in protein synthesis were found to be labelled. Accumulation of silver grains occurred at apical portion of the epithelial cells showed accumulation of silver grains after 6 hrs. of estradiol treatment, but not on cell surface. The endometrial stromal cells localized around the blastocyst also showed a peak of 3H-leucine incorporation 6 hrs. after estradiol, but not in the cells localized at interimplantation sites. No increased labeling was seen on the components of extra-cellular matrix at ultrastructural level. The present radioautographic experiment showed that epithelial and stromal cells localized in the endometrium of implantation chamber, changed their pattern of protein synthesis under nidatory estradiol effects. This evidence suggests that the phenomenon of implantation window induced by estradiol, is not a systemic response of the whole pregnant endometrium. The activation involves only a specific population of the endometrial cells localized just around the conceptus. PMID- 8467237 TI - Synaptic and non-synaptic immunolocalization of GABA and glutamate acid decarboxylase (GAD) in cerebellar cortex of rat. AB - The existence of a large number of GABA receptors in the cerebellar molecular layer, and the observation of numerous punctate immunoreactive deposits of GABA synthesizing enzyme (GAD) throughout this layer, could indicate the existence of numerous axon terminals that may be involved in neurotransmission modulated by GABA. These axon terminals may be different from those considered classically as cerebellar GABAergic axon terminals. Therefore, we have reinvestigated the localization of GABA- and GAD-immunoreactivities in the cerebellar cortex of the rat with the PAP method, using different antisera obtained from rabbits immunized with GABA, baclofen and GAD. The results observed in our investigation have demonstrated GABA- and GAD-immunoreactivities in the axon terminals considered classically as GABAergic, as well as in others which, until now, have not been considered GABAergic. This fact leads us to think that the distribution of GABA or molecules structurally similar to GABA is far more extended than previously thought in the cerebellum. We have also observed both GABA- and GAD immunoreactivities within dendrites and glial cells. These facts suggest us a possible extrasynaptic release of GABA. PMID- 8467238 TI - Alkaline phosphatase activity at physiological pH: kinetic properties and biological significance. AB - The activity of rat liver alkaline phosphatase (ALP) was studied at physiological pH, using para-nitrophenyl phosphate (pNPP) as substrate. At this pH, the purified enzyme had optimal catalytic efficiency and its activity was maximal for the very low substrate concentrations. During thermal inactivation of rat liver plasma membranes activities, the ratio of the measured residual activities (pH 10.5/pH 7.5) varied, showing that ALP was not the only plasma membranes pNPP hydrolase. Indeed, the proportion of pNPP hydrolase activities attributable to ALP in plasma membranes at pH 7.5 was relatively low. Effectively, it was shown using bromolevamisole, a potent and specific inhibitor of ALP, that contrary to what it was previously reported, ALP was not the major pNPP hydrolase of liver plasma membrane. PMID- 8467239 TI - A peptide containing the leucine zipper domain specifically inhibits CREB binding and transcription. AB - Formation of dimers via leucine zippers is an absolute requirement for several transcription factors to express their activity. Using circular dichroism spectroscopy, it was found that synthetic peptides which mimic the leucine zippers from CREB, Jun and Myc are alpha-helices in solution. The CREB leucine zipper peptide specifically inhibited the binding of wild type CREB protein and transcription from the CRE containing c-fos promoter in vitro. This inhibition is most likely caused by competition of the peptide to form complex with CREB monomers through leucine zippers. PMID- 8467240 TI - Electron microscopic radioautographic study on DNA synthesis in perinatal mouse retina. AB - For the purpose of comparing the quantitative changes in both labelled and unlabelled retinal cells with 3H-thymidine radioautography, normal ddY mice from early embryonic stage (E 9.5) to postnatal 2 weeks were utilized as materials. About 200 electron microscopic radioautograms were taken from the middle portions of retina in the early embryonic stages and from the inner half of outer neuroblastic layers of retina of 9 groups of litter mice at the late embryonic and postnatal ages, and the enlarged photographs were quantitatively analyzed by image analysis. The results showed that the area of nuclei, cytoplasm, mitochondria and the number of mitochondria, per retinal cell, decreased from early embryonic stages to postnatal ages in both labelled and unlabelled cells (p < 0.05). However, no significant changes occurred in the area of ER per retinal cell in both labelled and unlabeled cells. Significant differences of the ultrastructural changes between labelled and unlabelled cells were not statistically detected except the area of nuclei at P 1 and the number of mitochondria at P 3. PMID- 8467241 TI - Effects of two peroxisome proliferators (ciprofibrate and fenofibrate) on peroxisomal membrane proteins and dihydroxyacetone-phosphate acyl-transferase activity in rat liver. AB - The effects of ciprofibrate and fenofibrate, which are more potent peroxisome proliferators than clofibrate, on the activities of dihydroxyacetone-phosphate acyl-transferase (DHAP-AT) and glycerol-3-phosphate acyl-transferase (G3P-AT) were studied at the two pH optima 5.5 and 7.4 in subcellular fractions of rat liver, and in solubilized peroxisomal membranes (PMP) as well. Protein was also analyzed by gel electrophoresis. 1) Under the conditions of the specific activity of peroxisomal acyl-CoA oxidase (CN(-)-ACO) being increased (8 to 9-fold), there was no specific induction of the DHAP-AT activity when measured at pH 5.5 in purified peroxisomes and PMP. However, the total activities of DHAP-AT in these two fractions were increased by 6 to 11 times, as a result of hepatomegaly and peroxisome proliferation. In contrast, they were only slightly enhanced (x 1.1 to 2.2-fold) when determined at pH 7.4. The magnitude of the effects of a fibrate treatment was, therefore, dependent on the pH of the incubation medium. 2) Experiments of reversibility of enzyme induction reinforced the finding that the peroxisomal DHAP-AT activity is not specifically induced by ciprofibrate and fenofibrate. 3) Our results suggest the existence of a peroxisomal G3P-AT, non inducible by fibrates, in the rat liver. 4) Induction of peroxisomal membrane associated polypeptides with apparent molecular masses of 26- and 36-kDa was evidenced in stained electrophoretic gels of protein. PMID- 8467242 TI - Light microscopic radioautographic study of DNA synthesis in the kidneys of aging mice. AB - The change of proliferative activity in mouse kidney cortex cells during development and aging was studied by detecting S-phase cells by light microscopic radioautography using 3H-thymidine (3H-TDR). Mouse kidney tissues of various ages: prenatal 13.5, 15.5 and 19.0 days of gestation, postnatal 1 and 8 days, 1 and 2 months, and 1 year were used for this experiment. The kidney cortex tissues were labelled with 3H-TDR either in vitro or in vivo and they were processed for light microscopic radioautography. The labeling indices of the respective cell types were calculated. The labeling indices in glomeruli and uriniferous tubules in the superficial layer were higher than those in the deep layer of metanephric cortex through the developmental stages. However, they decreased rapidly after birth and reached low levels (below 4%) from 1 day to 1 year. PMID- 8467243 TI - Production of a new monoclonal antibody recognizing alpha-actinin: analysis of the changes in subcellular expression in the developing chick heart. AB - A new monoclonal antibody that recognizes alpha-actinin in cardiac muscle cells was used in a quantitative study (fluorescence activated cell sorting and polyacrylamide gel electrophoresis) of the expression of this protein during chick embryo development, to determine the changes in cytoplasmic and cytoskeletal compartments. alpha-Actinin expression was weak in early stages of development (Hamburger and Hamilton stage 18) and increased steadily until Hamburger Hamilton stage 40. In all stages, the protein was more abundant in the cytoplasmic compartment. The monoclonal antibody cross-reacted with alpha-actinin in chicken smooth and striated muscle cells and also showed a faint cross reaction with human cardiac muscle alpha-actinin. PMID- 8467244 TI - Predictors of toenail selenium levels in men and women. AB - Potential predictors of toenail selenium levels were studied in 1211 men and 1248 women aged 55-69 years. These subjects were randomly selected cohort members without prevalent cancer (other than skin) participating in a prospective study on diet and cancer in the Netherlands. Information on the considered potential predictors (gender, age, smoking, intake of dietary selenium and alcohol, Quetelet index) was collected together with toenail specimens in 1986. The average toenail selenium concentration was significantly (P < 0.001) lower in men than in women: 0.547 +/- 0.126 microgram/g (mean +/- SD) and 0.575 +/- 0.109 microgram/g, respectively. The gender difference remained significant after adjustment for the other variables in multiple regression analyses. Age was not associated with toenail selenium levels in men or women. An inverse association was observed with current smoking but not with past smoking. The average toenail selenium values for male current smokers were 0.513 +/- 0.106 microgram/g (mean +/- SD) versus 0.571 +/- 0.133 microgram/g for male never- or ex-smokers (P < 0.001). For women these values were 0.548 +/- 0.101 and 0.581 +/- 0.109 microgram/g, respectively (P < 0.001). Dietary selenium intake was positively associated with toenail selenium levels in multivariate analyses (P < 0.001), but the association was weak (partial r = 0.09). Alcohol intake and Quetelet index were not significant independent predictors of toenail selenium. The observed associations had similar directions in men and women but were stronger in men. PMID- 8467245 TI - Serum pepsinogens in relation to precancerous gastric lesions in a population at high risk for gastric cancer. AB - Concentrations of serum pepsinogens (PG) I and II were determined for 3252 randomly selected adults who participated in a population-based gastroscopic screening in an area of China with one of the world's highest rates of gastric cancer. PG I and II concentrations in both sexes tended to be higher than reported in other countries, with levels generally higher among males than females. PG I tended to decrease and PG II to increase with age, but the most pronounced associations were between PG I:II ratios and gastric histology. Median PG I:II ratios monotonically declined from 9.1 to 7.2 to 5.7 to 5.4 to 3.8 among those with superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia, and stomach cancer, respectively. The prevalence of dysplasia was nearly 3 times greater among those with PG I:II ratios less than 3 compared with those whose PG I:II ratios were greater than 10. While average levels differed significantly among the histologic groups, the PG I:II ratios were neither sensitive nor specific markers of an individual's likelihood of advanced gastric lesions in this population. PMID- 8467246 TI - Serum anti-Helicobacter pylori IgG antibodies and pepsinogens A and C as serological markers of chronic atrophic gastritis. AB - This study was designed to test the sensitivity and specificity of serum anti Helicobacter pylori IgG antibodies and the ratio of serum pepsinogen A to pepsinogen C (PGA:PGC) in detecting chronic atrophic gastritis (CAG) and intestinal metaplasia. Parallel gastric biopsies and a serum sample were collected from a series of 87 patients aged 20-69 years attending a routine upper endoscopy clinic. The seroprevalence (> 10 micrograms IgG/ml) of anti-H. pylori antibodies was 42.7%, and of a low PGA:PGC ratio (< 1.5) was 17.7%. A positive H. pylori IgG antibody level was more sensitive than the level of PGA:PGC in diagnosing CAG (71.4% and 25.0%, respectively), moderate CAG (86.7% and 26.7%, respectively), and intestinal metaplasia (90.9% and 50.0%, respectively). Anti-H. pylori IgG antibody levels were less specific than PGA:PGC levels in diagnosing CAG (90.9% and 93.9%, respectively), moderate CAG (78.3% and 89.1%, respectively), and intestinal metaplasia (72.6% and 92.2%, respectively). A combination of anti-H. pylori antibodies and a low PGA:PGC ratio for the detection of CAG resulted in a specificity of 100%, but the sensitivity was 21.4%. PMID- 8467247 TI - Procollagen type I carboxy-terminal propeptide as a marker of osteoblastic bone metastases. AB - Collagen type I is the sole collagen type found in bones and tendons. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it can be measured. According to current knowledge, PICP correlates with bone collagen synthesis and bone formation rate. Elevated serum levels of PICP in patients with Paget's disease, compared with normal subjects and correlated with serum alkaline phosphatase (Alk.Ph.), have been previously described. Thus, PICP may be a valuable marker of bone formation. PICP, serum Alk.Ph., serum bone Gla protein and 24-h urinary hydroxyproline:creatinine ratio have been measured in 47 cancer patients: 27 with predominantly osteolytic lesions (5 myeloma, 15 breast, 3 lung, 2 kidney, 1 bladder, 1 thyroid) and 20 with predominantly osteoblastic lesions (18 prostate and 2 breast). The higher levels of PICP were noted in patients with osteoblastic or mixed metastases. In the entire group of patients, a statistically significant correlation between PICP and bone Gla protein (r = 0.57; P < 0.001), PICP and Alk.Ph. (r = 0.80; P < 0.001), and bone Gla protein and Alk.Ph. (r = 0.44; P < 0.01) was noted. In those patients with osteoblastic metastases we observed a significant correlation only between PICP and Alk.Ph. (r = 0.62; P < 0.003). During chemotherapy, 13 of 20 patients with osteoblastic metastases who achieved objective response or stable disease showed a more rapid and significant decrease in PICP with respect to the other bone markers. Serum PICP level could be considered a good marker of osteoblastic activity. PMID- 8467249 TI - Micronutrient concentrations in paired skin and plasma of patients with actinic keratoses: effect of prolonged retinol supplementation. AB - Much of our knowledge about the relationship between micronutrients and cancer comes from studies in which plasma (serum) micronutrient levels have been correlated with cancer incidence; however, the relationship between the concentrations of micronutrients in the plasma and in the target tissues has not been established. Ninety-three subjects (62 males and 31 females ages 42-86, median age 69) with actinic keratoses were recruited for investigation of this relationship. The subjects were randomly assigned and received placebo or retinol (25,000 IU/day) intervention for 48 to 65 months as part of a skin cancer chemoprevention trial. Shortly before the end of the trial, three fasting plasma samples and one skin biopsy were obtained from each subject. The concentrations of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta carotene, cis-beta-carotene, retinol, retinyl palmitate, alpha-tocopherol and gamma-tocopherol in the plasma and skin were simultaneously measured using HPLC. The profiles of the eleven micronutrients in the plasma and skin were similar. Lycopene, beta-carotene and alpha-tocopherol were the predominant micronutrients in both plasma and skin, but the ratio of retinyl palmitate to retinol was much greater in the skin than plasma. The three fasting plasma concentrations from the same subject during a one-month period were very consistent; however, the between person variations were very large. The retinol supplementation caused a significant increase in the plasma concentrations of retinol, retinyl palmitate, lutein and alpha-tocopherol, especially retinyl palmitate as well as the skin concentrations of retinol and retinyl palmitate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467248 TI - A nonsaponification method for the determination of carotenoids, retinoids, and tocopherols in solid human tissues. AB - There has been an increasing interest in the measurement of carotenoids, retinoids, and tocopherols in human tissues because some of these micronutrients have been shown to have chemopreventive activity. Since clinical tissue samples obtained for analysis are usually small in quantity, a sensitive analytical procedure that can simultaneously measure all the micronutrients of interest in one small piece of human tissue is necessary. Moreover, some solid tissues, such as skin, are very difficult to homogenize unless they are first saponified in alcoholic KOH, but the saponification often causes substantial destruction of some micronutrients. Thus, a nonsaponification procedure using collagenase to facilitate homogenization was developed. Solid tissues are first incubated in a collagenase solution, homogenized, then incubated in a protease solution, followed by precipitation of tissue proteins and extraction with hexane. Collagenase digestion facilitates homogenization, and protease digestion increases the extractable amounts of the micronutrients from certain tissue samples. In this study, the recovery and precision (coefficient of variation) of the new procedure was determined. In addition, the extracted amounts of seven carotenoids, two retinoids, and two tocopherols from human skin, cervical/ovarian tissue, as well as sarcoma and kidney tumors using the new procedure and a commonly applied saponification procedure were compared. PMID- 8467250 TI - Impact of an HMO-based intervention to increase mammography utilization. AB - A health maintenance organization (HMO)-based program designed to increase breast cancer screening was evaluated, focusing on changes in mammography utilization. The program consisted of a multistage intervention aimed at women members and primary care physicians of the HMO. This report examines the effect of the intervention on mammography utilization. The program was evaluated using a quasiexperimental design in which a random sample of women aged 50-74 from the HMO (intervention) was compared to a similarly aged geographic control group selected through random digit dialing. From 1988 to 1990, 450 intervention women and 450 control women were sampled (without replacement) each year and surveyed about breast cancer screening practices and related knowledge. A clear increase in self-reported mammography utilization was associated with the intervention. The percentage of women who reported a mammogram in the 12 months prior to the survey increased from 41% in 1988 (baseline) to 68% in 1990 among HMO women, compared to a change from 39% to 49% among control women. Comparing postintervention rates of mammography in HMO versus control women yielded a rate ratio (RR) of 1.4. However, this effect was strongly modified by income and race. Women with annual incomes of $31,000 or more showed little (whites, RR = 1.2) or no (blacks, RR = 1.0) effect of the intervention. Among women with incomes less than $31,000, the effect among whites (RR = 1.9) was much stronger than among blacks (RR = 1.2). PMID- 8467252 TI - Alcohol abstainers: a low-risk group for cancer--a cohort study of Norwegian teetotalers. AB - Groups with assumed health-protective life-styles have been studied for several decades, in search of causes for cancer. We have analyzed cancer incidence, total mortality, and cause-specific mortality in Norwegian teetotalers to assess the possible health gains from an alcohol-abstaining life-style. A cohort of 5332 members of the International Organization of Good Templars was followed for 10 years from 1980. The cancer incidence and the cause-specific mortality of the cohort has been compared to that of the total Norwegian population. The standardized incidence ratio (SIR) for all cancer sites was 74 [95% confidence interval (CI), 64-80] for men and 72 (95% CI, 61-84) for women. For possible alcohol-associated cancers, such as cancer of the oral cavity, pharynx, esophagus, liver, and larynx, the SIR was 43 (95% CI, 17-88) for both sexes combined. For lung cancer the SIR was 57 (95% CI, 37-90) for men and 10 (95% CI, 0-57) for women. When all alcohol- and tobacco-associated cancers were excluded, the SIR for both sexes combined was 79 (95% CI, 69-87). The standardized mortality ratio for total mortality was 81 (95% CI, 65-74). This significant decrease in total mortality was caused by reduced risks for all major causes of death. The study indicates that members of the Norwegian chapter of the International Organization of Good Templars are a low-risk group not only regarding alcohol- and tobacco-associated cancers, but also regarding all other cancers. PMID- 8467251 TI - Epidemiology of colorectal adenomatous polyps. PMID- 8467253 TI - Dysplastic nevi in relation to superficial spreading melanoma. AB - The aim of the present study was to evaluate the frequency with which histologically confirmed dysplastic nevi are observed among patients with superficial spreading melanoma compared to patients with nodular melanoma. A pathology review of 117 new cases of first primary nonfamilial cutaneous melanoma identified 61 patients with superficial spreading melanoma and 19 with nodular melanoma. Study participants received a physician-conducted skin examination which included enumeration of clinically benign and atypical nevi and the surgical excision of the clinically most atypical nevus. Patients' dysplastic nevus status was established by histological review of the clinically most atypical nevus. A comparison based on the tumor subtypes showed that dysplastic nevi occur nearly four times more frequently among patients with a prior diagnosis of superficial spreading melanoma relative to nodular melanoma (odds ratio = 3.6; P = 0.03). PMID- 8467254 TI - Competency and the law. PMID- 8467255 TI - Six "musts" for quality programs. PMID- 8467256 TI - Conducting a computer needs assessment. PMID- 8467257 TI - Implementing the Patient Self-Determination Act. PMID- 8467258 TI - Restraint/seclusion: an approach to documentation and assessment. PMID- 8467259 TI - Strategies to keep a group alive. PMID- 8467260 TI - Trends in evaluating quality of care. PMID- 8467261 TI - Ten tips for using the AHCPR guidelines. PMID- 8467263 TI - Preestablished forms help quality monitoring. PMID- 8467262 TI - Finding the facts on computer software. PMID- 8467264 TI - JCAHO unveils new standards for orientation, education and training. PMID- 8467265 TI - Ten characteristics of true team players. PMID- 8467266 TI - Combining staff development and support services for improved outcomes. PMID- 8467267 TI - Twenty-five tips from expert preceptors. PMID- 8467268 TI - Ethical issues in staff development. PMID- 8467269 TI - Tic-tac-toe: a terrific teaching technique. PMID- 8467270 TI - The reduction of aggression in people with learning difficulties: a review of psychological methods. AB - The literature on the reduction of aggression in people with learning difficulties is reviewed. The methods of reducing aggression identified were predominantly evaluated in staffed settings and with target behaviours more frequent than once a day. This contrasts with the findings of a recent survey that found the majority of aggressive individuals to live in the community and show aggression less than once a day. It is argued that the reasons for this disparity are as follows. That it is easier to do a controlled study in staffed settings with high-frequency aggression. That it is more difficult to do an analysis of the target behaviour if it is low frequency or if the subject is in the community; and that the methods that have been traditionally used to reduce aggression may not be effective with all subjects in all settings. It is suggested that it may be necessary to develop and evaluate a new technology for reducing aggression. PMID- 8467271 TI - Understanding women's responses to treatment for cervical intra-epithelial neoplasia. AB - Laser treatment is held to prevent the development of cervical intra-epithelial neoplasia, or CIN, into invasive carcinoma of the cervix. Recent work has found that such treatment represents a considerable emotional upset in the lives of many women. In this study, the impact of treatment was further investigated, using a control group to separate the effects of diagnosis from those of treatment. The main findings showed that the diagnosis of CIN is traumatic. Women experience high levels of intrusive thoughts and avoidance, and in response to perceived threats to their health, and existing beliefs about themselves, they also experience high levels of anger. An impact of treatment over and above that of diagnosis was not found. From the interview data, diagnosis has its traumatic impact through women's understanding of CIN's association with cervical cancer, a potentially life-threatening disease. Interview data also suggest that body image and sexual relationships suffer following diagnosis because of CIN's postulated causal relationship to the sexually transmitted wart virus. Fear of the progression of CIN to cervical cancer is consistent with the medical model which provides the rationale for preventative laser treatment. It is speculated that once women are diagnosed as having CIN, the spectre of cancer is raised and their anxiety may be such that being monitored and not immediately treated may cause them great distress. PMID- 8467272 TI - Dieting, dietary restraint and cognitive performance. AB - In a volunteer sample of female undergraduates, concerns about eating, body weight and body shape were found to increase with the level of self-reported dietary restraint. These concerns were greatest, however, in a subsample of subjects who were currently dieting to lose weight, and greater than in equally restrained but non-dieting subjects. Furthermore, the dieting subjects performed less well on a demanding cognitive task than the non-dieting subjects. These results show that it is important to distinguish between dietary restraint and actual dieting behaviour. They also highlight the need for further research to examine the effects of dieting on cognitive functioning. PMID- 8467273 TI - Subjective craving for opiates: evaluation of a cue exposure protocol for use with detoxified opiate addicts. AB - Cue exposure has been advocated as an intervention for reducing relapse rates in detoxified addicts, by extinguishing classically conditioned drug effects/craving which may have developed. Several studies with alcoholics have found cue exposure to be associated with reductions in craving, but no controlled study has yet shown such an effect in opiate addicts. The present controlled group design evaluates a protocol which draws from experience in the treatment of anxiety and requires that each stimulus exposure should be continued until within-session habituation has occurred. It also explores whether there is any benefit of using a 'cognitive aversion' strategy during cue exposure, based on the social learning analysis that craving derives from expectancies of positive drug effects. A total of 21 detoxified in-patients were randomized to routine ward treatment plus two sessions of either cue exposure (Group E) or cue exposure and cognitive aversion (Group E/CA), or to routine treatment alone (Group C). A specially designed Craving Test was carried out before and after treatment, to assess change in cue elicited reactions. The two treated groups showed significantly greater reductions in craving than Group C, but did not differ from each other. The cue exposure protocol has therefore been adopted for use in an ongoing clinical trial. PMID- 8467274 TI - The Spot-the-Word test: a robust estimate of verbal intelligence based on lexical decision. AB - The development of a test aimed at estimating premorbid intelligence is described. The test, Spot-the-Word, involves presenting the subject with pairs of items comprising one word and one non-word, and requiring the subject to identify the word. Data show that performance correlates highly with verbal intelligence as estimated by Mill Hill Vocabulary score and by performance on the National Adult Reading Test (NART). Performance does not decline with age, in contrast to an associated test of verbal recognition memory. A second study attempted to test the effect of intellectual deterioration due to age on Spot-the-Word performance. Elderly subjects who had high vocabulary scores scored well on the Spot-the-Word regardless of whether fluid intelligence as measured by the AH4 test was well preserved, or was low, implying intellectual deterioration. A final study collected normative data on a sample of 224 subjects stratified by age and socio economic status, with each subject performing two parallel forms of the test, A and B, together with the NART. Correlation between the two forms was .884, while correlation with NART was .831 for Form A and .859 for Form B, suggesting adequate reliability and validity. It is concluded that the test provides a potentially useful additional method of estimating premorbid intelligence. PMID- 8467275 TI - Reduced cognitive inhibition in obsessive-compulsive disorder. AB - On a semantic negative priming task designed to investigate putative inhibitory mechanisms of selective attention, obsessive-compulsive disordered (OCD) subjects were distinguished from all other sub-categories of anxiety disorder (OAD). OCD subjects failed to show any priming effects in the repetition priming condition and exhibited facilitation in the semantic priming condition (i.e. shorter reaction times to previously ignored stimuli). OAD subjects demonstrated negative priming (i.e. longer reaction times to previously ignored stimuli) in both experimental conditions. These results are interpreted in terms of reduced cognitive inhibition in OCD and the implications of this hypothesis are discussed. Parallels are also drawn with previous studies regarding the results of high schizotypes and schizophrenic subjects using negative priming tasks. PMID- 8467276 TI - Correlates of everyday memory among residents of Part III homes. AB - Performance on the Rivermead Behavioural Memory Test (RBMT) of 43 residents of Part III homes was compared with performance on Raven's Coloured Progressive matrices and the National Adult Reading Test (NART). Health, medication, selfcare and social activity were also measured. Results show that although Raven's score was the best predictor of memory test performance, it had a high refusal rate. Age was not a significant predictor of overall memory test score but results were complicated by age of entry into Part III, with older people performing better on some items. Medication, in particular drugs acting on the central nervous system, enhanced performance on some items. PMID- 8467277 TI - The relationship between Beck's concepts of sociotropy and autonomy and the NEO Personality Inventory. AB - Beck (1983) proposed that two personality dimensions, sociotropy and autonomy, represent vulnerability factors for depression. This study assesses the relations between sociotropy/autonomy (Sociotropy/Autonomy scale) and five personality dimensions, i.e. neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness (NEO-Personality Inventory). Sociotropy was related positively to neuroticism and negatively to openness to experience. Autonomy was positively associated with conscientiousness. PMID- 8467278 TI - Deriving principal component IQ scores from the WAIS-R. PMID- 8467279 TI - Health beliefs, locus of control, emotional control and women's cancer screening behaviour. AB - Improvements in women's cancer-screening behaviours can lead to a reduction in the incidence of breast and cervical cancer. This paper considers the utility of three social psychological models as predictors of such behaviours. Almost 400 women throughout Northern Ireland completed a questionnaire designed to measure the extent of their cancer-screening behaviour, their health beliefs about cancer, their health locus of control and their emotional control. It was found that several components of the health belief model and of locus of control were predictors of the behaviours. The most important predictor of breast self examination was confidence in how to practise BSE while the most important predictor of attendance for cervical smears was lack of fear of the consequences of the investigation. The findings are discussed with reference to attempts to promote these practices. PMID- 8467280 TI - BMT in experimental autoimmune diseases. PMID- 8467281 TI - Is there an effective therapy for chronic graft-versus-host disease? PMID- 8467282 TI - Physiological mechanisms in BMT and haemopoiesis--revisited. PMID- 8467283 TI - Pulmonary thromboembolism in leukaemic children undergoing bone marrow transplantation. AB - Of 67 leukaemic children transplanted in our BMT unit 3 presented with severe acute respiratory syndrome associated with pulmonary thromboembolism (PTE) as diagnosed by scintiscan and/or angiography in the first month after BMT. Intervention with continuous positive pressure ventilation, urokinase (loading dose, then continuous infusion for 12-18 h) and heparin (continuous infusion for an average of 10 days) has been carried out successfully in two cases. In conclusion, when evaluating patients undergoing BMT and developing early pulmonary complications, PTE must be considered. The pathogenesis of PTE is still difficult to ascertain but urokinase therapy may reduce early morbidity. PMID- 8467284 TI - Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, ara-C, cyclophosphamide) +/- TBI and autologous BMT for malignant lymphomas. AB - Twenty-four patients autografted for malignant lymphoma have been followed. All were conditioned with BEAC (BCNU, etoposide, ara-C, cyclophosphamide), in 10 patients combined with total body irradiation (TBI) 7.5 Gy. Within 1 month of ABMT, a capillary leak syndrome was seen in four patients (one death) and isolated pericarditis in one. Nineteen patients survive disease-free at > or = 6 months, median (range) 24 (11-48) months. In 15 of 19 patients, a decrease in glomerular filtration rate (GFR) of > 20% was observed, 6 (6-24) months after ABMT. In six of these patients (five treated with TBI), the renal dysfunction was still progressing 11-36 months after ABMT. Five patients (four conditioned with TBI) developed a haemolytic uraemic syndrome (HUS) with Coombs negative haemolytic anaemia, platelet consumption and renal impairment, with onset 3-6 months after ABMT. Haemolysis and platelet consumption, but not renal impairment, were reversible in all patients. One death from HUS was seen. Because of the adverse effects described we have abandoned the combination of BEAC with TBI. PMID- 8467285 TI - Prognostic importance of histological and immunopathological assessment of skin and rectal biopsies in patients with GVHD. AB - Skin and rectal biopsies from patients with GVHD were examined histologically and immunopathologically before and after treatment for the disease. The patients were divided into two groups: those showing a good response to treatment and those showing a poor or no response. The aims of the study were to assess the possibility of predicting the response to treatment and to compare good and poor responders after treatment. The results show that there are no features on either skin or rectal biopsy that could identify those patients with early GVHD who would respond to treatment. Following treatment with steroids there was no change histologically in the grading of the skin biopsy whereas the rectal biopsy showed improvement in six of nine good responders and no improvement in the poor responders. There was an increase in infiltrating lymphocytes in both the skin and rectum of patients showing a poor response and this is most likely due to the ongoing immune reaction. The pre-treatment biopsy did not show any features that would predict this development and was therefore of no prognostic value. However, examination of skin and rectal biopsies may aid in determining whether patients are responding to the treatment given for GVHD. PMID- 8467286 TI - Use of granulocyte-macrophage colony-stimulating factor and erythropoietin in combination after autologous marrow transplantation. AB - The toxicities and possible utility of the combination of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human erythropoietin (rHuEPO) given after autologous BMT were evaluated in this pilot trial. Eighteen patients received the combination and were compared with six concurrent control and 65 historical control patients treated with rhGM-CSF alone. Patients treated with the combination tended to have more rapid recovery to an absolute neutrophil count of 500 x 10(6)/l (median = 12.5 vs 18 days for concurrent and 19 days for historical control patients). There was no apparent impact on red cell transfusion requirements, platelet recovery or duration of hospitalization. Patients treated in the current study with rhGM-CSF plus either rHuEPO or with placebo had a higher incidence of rash than seen in our historical experience using rhGM-CSF. This difference may reflect changes in the source of rhGM-CSF or in the infusion schedule. Erythropoietin can be combined safely with rhGM-CSF after autologous transplantation. Larger controlled trials will be necessary to detect possible therapeutic effects. PMID- 8467287 TI - Parafollicular hair bulge in human GVHD: a stem cell-rich primary target. AB - We sought to determine the frequency of parafollicular hair bulge involvement in human GVHD of the skin. The parafollicular bulge was recently shown by Murphy to be a target of GVHD in the minor histoincompatible mouse GVHD model. We sought a crude estimate of this frequency by studying 541 skin biopsy reports from a 5 month period at our bone marrow transplant center. We selected 170 slides for review on the basis of a prior histological diagnosis of GVHD. Of these 41 had potentially evaluable pilar units and were recut. Three cases were considered unevaluable but the remaining 38 cases all showed positive evidence of involvement of the parafollicular hair bulge. The data confirm that the parafollicular hair bulge is involved with very high frequency in acute GVHD in humans. PMID- 8467288 TI - Consequences of cryopreserving first remission autologous marrow for use after relapse in patients with acute myeloid leukemia. AB - Ninety-eight patients with AML had marrow harvested and cryopreserved at a median of 6 months (range 1-36 months) after achieving first CR with the intent of performing an ABMT at the first sign of relapse. Thirty-three of the 98 patients have not relapsed and 32 survive at a median of 64 months (range 10-105 months) after marrow storage. Sixty-five of the 98 patients relapsed at a median of 7 months (range 1-53 months) after marrow storage. The survival at 2 and 4 years for the 65 patients who relapsed was 22% and 8% respectively. Sixteen of 24 patients treated initially with chemotherapy were ultimately transplanted and two are surviving 21 and 41 months following ABMT and allogeneic marrow transplant respectively. There were no survivors among the eight patients treated with chemotherapy who were not transplanted. Thirty-eight of the 65 patients who relapsed proceeded directly to ABMT without attempts at remission induction, and eight survive disease-free 15-114 months following ABMT. One of the first 17 patients treated with cyclophosphamide and total body irradiation survives without relapse. The probabilities of relapse-free survival, non-relapse mortality, and relapse for the 17 most recent patients prepared with busulfan containing regimens were 41%, 39% and 32% respectively. Surviving patients had longer first remissions (p = 0.08) and lower peripheral blood blast counts at the time of transplant (p = 0.02) when compared with patients who died. These data suggest that ABMT in untreated first relapse is a reasonable approach for the treatment of patients with AML who relapse. PMID- 8467289 TI - Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. AB - Experimental allergic encephalomyelitis (EAE) was induced in Buffalo rats by immunization with syngeneic spinal cord homogenate in complete adjuvant. EAE, an autoimmune disease of the central nervous system (CNS), is regarded as a model for multiple sclerosis. When severe paresis had developed, rats were treated with high-dose total body irradiation (TBI) and transplanted with syngeneic BM from healthy donors. Nine Gy TBI followed by syngeneic BMT greatly accelerated recovery of paresis compared with untreated controls. In 6-33% of the treated animals a relapse of EAE was observed shortly after treatment. Reimmunization 20 days after treatment, resulted in a relapse in 12-44% of the rats. Employing the maximally tolerated dose of TBI (10 Gy) did not significantly alter the incidence of spontaneous or induced relapses. Furthermore, it was shown that irradiation of the CNS only was not sufficient for the induction of complete regression of paresis. The origin of the cells responsible for these relapses is discussed, as is the importance of reimmunization in evaluating the effect of treatment of experimental autoimmune disease. PMID- 8467290 TI - Graft failure following neutrophil-specific alloantigen mismatched allogeneic BMT. AB - We report a case of unexplained graft failure in a 33-year-old man who received an allogeneic bone marrow graft that contained a donor-recipient mismatch involving the highly immunogenic NA1 neutrophil-specific alloantigen system. Laboratory and clinical data suggest that an alloimmune process related to the neutrophil alloantigen mismatch played a role in the development of the graft failure. PMID- 8467291 TI - Successful allogeneic bone marrow transplantation in juvenile CML: conditioning or graft-versus-leukaemia effect? AB - Allogeneic BMT is the treatment of choice for juvenile CML (JCML). This has been successful following conditioning with cyclophosphamide (120 mg/kg) and total body irradiation (TBI) (10-15.75 Gy). However, busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) (Bu/Cy) conditioning has been reported to be insufficient to eradicate the malignant clone in JCML. We report successful BMT and eradication of the disease at 18 months follow-up in a child 15 months old at presentation, who was conditioned with busulphan 20 mg/kg and cyclophosphamide 200 mg/kg, with the addition of splenic irradiation. Despite using higher than conventional doses of busulphan, pharmacokinetic analysis revealed very low busulphan peak levels and rapid excretion. As a possible consequence, only partial chimerism was achieved, but full engraftment ensued following the discontinuation of cyclosporin A, rebound donor lymphocytosis and the onset of acute GVHD. We suggest that host resistance to engraftment and tumour elimination was overcome by removing a suppressive effect on donor lymphocytes, allowing a graft-versus-leukaemia effect. PMID- 8467292 TI - Folinic acid rescue after methotrexate. PMID- 8467293 TI - Thalidomide as therapy for intestinal chronic GVHD. PMID- 8467294 TI - Comparison of psychologic and physiologic functioning between patients with masticatory muscle pain and matched controls. AB - This study explored the physiologic and psychologic distinctions between masticatory muscle pain patients and age and sex-matched normal controls. Subjects completed several standardized psychologic tests. They then underwent a laboratory stress profile evaluation to obtain physiologic measures (EMG, heart rate, systolic and diastolic blood pressure) under conditions of rest, mental stress, and relaxation. The pain patients reported greater anxiety, especially cognitive symptoms, and feelings of muscle tension than did the controls. Under stress, pain patients had higher heart rates and systolic blood pressure than the controls. Electromyogram activity in the masseter regions was not significantly different between the pain and control group. The results are discussed in terms of the likely mechanisms that might account for the observed differences between masticatory pain patients and normal subjects. PMID- 8467295 TI - Temporomandibular joint pain assessment. AB - The aim of this study was to evaluate pain characteristics of patients with temporomandibular joint-related pain and propose a rationale for the assessment of pain and its impact on patients with temporomandibular disorders. Based on anamnestic information, the 88 patients in the sample were classified according to pain grade: (1) acute/subacute nonrecurrent or recurrent pain, n = 41 (46.6%); (2) persistently recurring pain in relatively high frequency, or nonsevere persistent pain, n = 32 (36.4%); (3) persistent and impairing pain, n = 8 (9.1%); (4) persistent and disabling pain, n = 7 (7.9%); and (5) persistent and handicapping pain, n = 0. Regarding TMJ pain provoked during the clinical examination, there was a significant difference among diagnostic subgroups, subgroups with different pain intensity levels, and pain grade subgroups, but no significant differences could be found based on the duration of the pain symptoms. Subgroups also did not significantly differ in scores on the Multi dimensional Pain Inventory and the General Health Questionnaire. Based on the results of the study, the assessment of nonchronic TMJ pain may generally be limited to an accurate description of the pain complaint and thorough clinical assessment. Multidimensional assessment may be useful when the TMJ pain persists or is persistently recurring. Depending on individual circumstances, additional assessment procedures may prove to be useful. A general strategy for pain assessment in temporomandibular disorders is proposed. PMID- 8467296 TI - Craniomandibular disorders in the geriatric patient. AB - This paper represents a general review of basic age-related changes that take place in the craniomandibular apparatus and the most frequently presenting conditions associated with craniomandibular disorders (CMD) in the elderly. The evaluation of geriatric patients with signs or symptoms of CMD must consider (1) normal age-related changes in the craniomandibular apparatus and their impact on both normal function and responses to stress; (2) the role of dentition status and dental prosthesis in CMD; and (3) the contribution of malignant disease, psoriasis, arthritic conditions, pseudogout, granulomatous vascular conditions, and metaplastic involvement of tissue to the pathosis of CMD. The clinician must also be aware of various effects of psychologic, sociologic, and biologic aspects of aging on the development of headache and atypical facial pain as components of CMD in the geriatric patient. PMID- 8467297 TI - Characterization of 86 bruxing patients with long-term study of their management with occlusal devices and other forms of therapy. AB - Of 353 patients screened, 86 answered positively to questions designed to identify bruxers. The bruxing patient profile revealed that 100% had working excursive interferences, 78% had balancing excursive interferences, and 95.4% had a premature contact into maximum intercuspation. Most of the bruxing patients had a chief complaint that related to pain, and 89.6% of the patients had a craniomandibular disorder. The patients were initially managed with an anterior deprogrammer and were later managed with other occlusal devices as signs and symptoms dictated. Definitive treatment was determined by the patient's maxillomandibular relationship. PMID- 8467298 TI - Clinical follow-up with different disc positions. AB - A clinical follow-up of 45 previously symptomatic patients with arthrographically diagnosed TMJ disc positions was performed at least 1 year (average, 4 years 4 months) after treatment. The patients were divided into three groups according to disc position: (1) superior disc position, n = 5; (2) anterior disc displacement with reduction, n = 17; and (3) anterior disc displacement without reduction, n = 23. Ninety-two percent of the patient were treated conservatively. Seventy percent of the patients reported being symptom-free or improved. The frequency of joint clicking did not change considerably, but the amount of crepitating sounds increased markedly. No difference was found regarding treatment outcome between the anterior disc displacement groups with and without reduction. PMID- 8467299 TI - Reproducibility of the condylar reference position. AB - The reproducibility of the condylar reference position was examined at the pont of unstrained hinging movement of the mandible in subjects with TMJ symptoms and in asymptomatic subjects. Three different operators performed the procedure to detect interoperator variability. Each operator made five registrations using computerized axiography in the electronic mandibular position indicator mode. Data were evaluated by an analysis of variance using three factors: (1) repetitions of the single operator, (2) data from symptomatic versus asymptomatic patients, and (3) values of different operators. The results showed that none of these factors had a significant influence on reproducibility of the condylar reference position. High reproducibility was obtained in both symptomatic and asymptomatic groups. Measured values remained within +/- 0.1 mm in 58.6% and within +/- 0.2 mm in 24.3% of the registrations. PMID- 8467300 TI - Thermographic characterization of the asymptomatic temporomandibular joint. AB - This study used electronic thermography, an alternative diagnostic imaging modality, to assess the thermal image characteristics of the normal TMJ in 30 asymptomatic subjects. Assessments made included: thermal pattern recognition and symmetry, absolute temperature measurements and differences in absolute temperature measurements, and mean temperature measurements and differences in five anatomic zones. Results indicated the presence of a common thermal TMJ pattern in two thirds of patients, with variations from this pattern in the remaining patients. All TMJ thermal patterns demonstrated marked thermal symmetry, with delta T < 0.2 degrees C in the region of the TMJ and related regions of the face. This consistent symmetry demonstrated in normal subjects suggests that substantial thermal asymmetry may prove to be a reliable indicator of TMJ disease. PMID- 8467301 TI - Changes in subjective symptoms of craniomandibular disorders in children and adolescents during a 10-year period. AB - An epidemiologic sample of 293 subjects in three age groups, now 17, 21, and 25 years of age, were followed longitudinally with respect to symptoms of craniomandibular dysfunction during a 10-year period. Reports of one or more such symptoms increased in all three age groups during the 10 years. At the follow-up, 1 in 3 individuals in all three groups had noticed such symptoms occasionally and 10% had them frequently. Reports of oral parafunctions such as bruxing and clenching also increased, while other parafunctions such as nail, lip, cheek, and tongue biting increased from the age of 7 to 11 but then decreased with age. Despite the high incidence of subjective symptoms of craniomandibular disorders, only a few subjects had had any kind of functional treatment performed during the 10-year period, and only 7 had an actual demand for treatment at present. PMID- 8467303 TI - Activity of anterior temporalis and masseter muscles during deliberate unilateral mastication. AB - The reproducibility of electromyographic parameters descriptive of deliberate unilateral chewing (activity, timing, curve symmetry) was investigated in normal asymptomatic volunteers. The best time for the initiation of muscle activity was also examined, with the future aim of staging TMJ internal derangements. The results suggest that activity is the most reliable variable, indicating that it may be helpful in describing muscle incoordination. When time was used in conjunction with another variable, overall reproducibility decreased. PMID- 8467302 TI - Management of craniomandibular disorders. Part 1: A craniocervical dysfunction index. AB - A craniocervical dysfunction index has been developed (based on the Helkimo Dysfunction Index) to comprehensively assess craniocervical dysfunction and to objectively monitor the management of patients who present with these clinical problems. The close functional interrelationship of temporomandibular joints, jaw muscles, and cervical joints and muscles is reviewed, and a mechanism is proposed to explain dysfunctional relationships between these structures. This is the first of three papers stemming from a clinical study that investigated craniomandibular disorders and assessed the effect of routine dental management on craniomandibular and craniocervical dysfunction. PMID- 8467304 TI - Cold chain study: danger of freezing vaccines. PMID- 8467305 TI - Pharmacochemistry Meeting. Aspects of Metabolism Weesp, The Netherlands, 11 December 1992. Abstracts. PMID- 8467306 TI - Pharmaceutical and Biomedical Analysis Meeting. Tilburg, The Netherlands, 27 November 1992. Abstracts. PMID- 8467307 TI - Urinary dopamine and sodium excretion in spontaneously hypertensive rats. AB - We measured urinary dopamine in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before (days 0-6) and during high-salt diet, in the absence (days 6-10) and presence (days 10-14) of added L-dopa (2 mg/kg/day by gavage). Urinary excretion of sodium (UNaV) increased 20-fold during intake of chow containing 8% NaCl in both strains. Systolic blood pressure (SBP) of SHR increased slightly (9 +/- 4 mmHg; p < 0.05) on the high-salt diet, whereas SBP did not change in WKY. Urinary dopamine excretion was not different between strains in the basal state, and was as great or greater in SHR than WKY during high-salt intake with and without added L-dopa. SBP was unaffected by L-dopa administration and UNaV did not increase or differ between strains despite higher urinary dopamine excretion in SHR. We conclude that renal dopamine formation in vivo is not diminished in SHR, compared with WKY, on normal or high-salt diets, and that elevation of renal dopamine formation secondary to L-dopa administration is not associated with reductions in SBP or altered UNaV in these rats. PMID- 8467308 TI - Evaluation of a structured treatment and teaching programme on hypertension in general practice. AB - OBJECTIVE: Evaluation of a structured hypertension treatment and teaching programme in general practice. DESIGN: Prospective controlled trial; follow-up period 18 months. SETTING: 10 primary health care practices. PRACTICES AND PATIENTS: From each practice 20 patients (30 to 60 years old, mean of the last two blood pressure measurements at or above 160 and/or 95 mmHg) were randomly selected; in 5 practices these patients were to participate in the treatment and teaching programme; in the remaining 5 practices hypertension care was continued without the availability of such a programme (controls). INTERVENTION: Structured treatment and teaching programme based upon four group sessions for patients mainly conducted by paramedical personnel. MAIN OUTCOME MEASURES: Blood pressure, body weight, prescription of antihypertensive drugs - as documented in the patient's records. MAIN RESULTS: Of the 100 control patients 26 and of the 100 intervention patients 14 were lost to observation; 46 patients had agreed to participate in the programme. The mean number of prescribed antihypertensive agents per patient decreased in the intervention group (1.8 +/- 1.3 at baseline, vs 1.2 +/- 1.2 at follow-up) compared to the control group (1.6 +/- 1.3 vs 1.8 +/ 1.6); difference 0.8 (95% CI 0.4 to 1.1), p < 0.0001. In the control group 9% and in the intervention group 33% of patients had documented reductions of body weight (p < 0.0001). Blood pressure decreased in the intervention group (162 +/- 14/100 +/- 7 mmHg at baseline, vs 154 +/- 16/95 +/- 9 mmHg at follow-up) compared to the control group (161 +/- 13/98 +/- 7 mmHg vs 158 +/- 18/96 +/- 11 mmHg); differences for systolic blood pressure 5 (95% CI 0 to 10) mmHg, p = 0.071; for diastolic blood pressure 4 (1 to 7) mmHg, p = 0.018. CONCLUSIONS: The introduction of a structured hypertension treatment and teaching programme in general practice may lead to significant improvements of hypertension care. PMID- 8467309 TI - Ca2+ ATPase activity in essential and renal hypertension. AB - In 15 patients with essential hypertension, 16 patients with renal hypertension and in 12 healthy subjects Ca2+ ATPase activity was determined in red blood cells both in the basal state and after maximal stimulation with calmodulin. Normal subjects showed a basal and maximal activity of 7.1 +/- 3.6 and 16.0 +/- 2.3 pmol phosphate/min.10(6) RBC, respectively. Renal hypertensives had a similar basal Ca2+ ATPase activity (5.4 +/- 4.1 pmol phosphate/min.10(6) RBC) and a lowered maximal Ca2+ ATPase activity (9.8 +/- 5.4 pmol phosphate/min.10(6) RBC, p < 0.05). In essential hypertensives basal and maximal Ca2+ ATPase activity was 9.0 +/- 5.3 and 35.4 +/- 14.4 pmol phosphate/min.10(6) RBC, respectively, the latter being significantly increased (p < 0.01). This finding, which is in contrast to earlier results indicating a lowered Ca2+ ATPase activity in essential hypertension, may be explained as a consequence of an increased Ca2+ influx in essential hypertension. A lowered Ca2+ ATPase activity does not seem to be involved in the pathogenesis of essential hypertension. PMID- 8467310 TI - The effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) on the overall baroreflex system in anesthetized mongrel dogs. AB - The effects of alpha-hANP (0.3 micrograms/kg body weight/min) on the baroreflex system were studied in anesthetized dogs according to three different protocols. In the first protocol, the effects of alpha-hANP on an open-loop gain (G(AP)) of the overall baroreflex system and a gain (GHR) of the baroreflex heart rate control system during quick mild hemorrhage and blood infusion were studied. G(AP) was decreased from 7.6 +/- 0.6 to 2.8 +/- 0.5 by alpha-hANP with hemorrhage. G(AP) decreased 7.4 +/- 0.8 to 2.9 +/- 0.4 by alpha-hANP with blood infusion. G(AP) was restored nearly to the control levels one hour after alpha hANP administration. GHR did not change by alpha-hANP administration. In the second and third protocol, a site of action of alpha-hANP was analysed. alpha hANP inhibited the responses of systemic vascular resistance to quick mild hemorrhage and blood infusion, but did not affect the responses of cardiac output to quick mild hemorrhage and blood infusion in the second protocol. After carotid sinus denervation and vagotomy, alpha-hANP inhibited an arterial pressure responses to phenylephrine and nitroglycerin bolus injection in the third protocol. These findings suggest that alpha-hANP has mainly an effect on the peripheral vascular system to decrease its responsiveness, resulting in a decrease in G(AP). PMID- 8467311 TI - Acute and chronic effects of losartan (DuP 753) on blood pressure and vascular reactivity in normotensive rats. AB - The effects of in vivo treatment with the nonpeptide subtype 1 angiotensin II receptor antagonist, losartan, on blood pressure and vascular reactivity in normotensive male Sprague-Dawley rats were studied. Initial acute experiments demonstrated that blood pressure was significantly decreased six hours following a single injection of losartan (10 mg/kg, sc), but returned to control levels by 24 hours post-injection. Pressor responses to angiotensin II (0.1 ug/kg, iv) in these rats were significantly attenuated 2 and 24 hours following losartan injection. For chronic studies, rats were injected once daily for 21 days with either the same dose of losartan or saline vehicle. Blood pressure and pressor responses to angiotensin II were assessed at the end of the 21 day treatment period. A significant decrease in blood pressure was observed in chronic losartan treated rats 6 hours after the last injection on day 21; however, as in the acute studies, blood pressure had returned to control values by 24 hours post injection. Although blood pressure had returned to normal, pressor responses to angiotensin II were significantly attenuated in chronic losartan treated rats 24 hours after the last injection. Following the in vivo studies, aortae and tail arteries were removed for experiments on vascular reactivity. Acute and chronic losartan treatment had no effect on KCl and norepinephrine reactivity. Endothelial-dependent and independent relaxation responses were also unaltered. A significant decrease in the maximal contractile response to angiotensin II was observed in aorta from acute and chronic losartan treated rats. Electrical stimulation-induced responses were unaltered in tail arteries from rats acutely treated with losartan but were potentiated in rats chronically treated with losartan. Exogenously applied angiotensin II, in concentrations which did not elicit contractile responses, potentiated electrical stimulation-induced responses of tail arteries from control rats but did not influence responses in arteries from acute and chronic losartan treated rats. These results demonstrate that losartan has significant blood pressure lowering effects in normotensive rats. Interestingly, although blood pressure returns to normal by 24 hours post injection, pressor responses to angiotensin II remain attenuated in acute and chronic losartan treated rats. Finally, losartan treatment results in specific alterations in vascular reactivity associated with the actions of angiotensin II. PMID- 8467312 TI - The acute effect of nicardipine on the renin-angiotensin-aldosterone system in salt-sensitive essential hypertension. AB - To determine the role of the renin-angiotensin-aldosterone (RAA) system in the acute effect of calcium channel blockers, we examined the acute effect of 40 mg nicardipine in 21 essential hypertensive patients. Nine patients whose mean blood pressure (MBP) decreased more than 5% at 2 hours after 20 mg furosemide i.v. were classified as salt-sensitive (SS); the remainder as salt-resistant (SR). The percentage decrease of MBP with nicardipine was not different between the two subgroups (12.4 +/- 2.5% for SS, and 17.7 +/- 4.1% for SR). The percentage decrease of MBP correlated with the pretreatment MBP (r = 0.67, p < 0.001), but not with the basal plasma renin activity (PRA), plasma aldosterone concentration (PAC), or natriuretic response. A significant increase of heart rate was noted in SR (31.2%) but not in SS (6.5%), and was associated with a higher increase of PRA in SR (90.7%) than in SS (25.5%). A correlation between the increase of PRA and the percentage increase of heart rate was noted (r = 0.77 p < 0.001). Decrease of PAC was observed in SS but not in SR until the third hour. The 3-hour sodium excretion was slightly greater in SR than in SS (59.9 +/- 9.1 vs. 35.1 +/- 3.0 mEq; p < 0.05). In summary, the acute hypotensive effect of nicardipine is dependent upon the vascular tone regardless of the status of the RAA system. An increase in PRA by nicardipine resulting from a baroreflex mechanism may counteract the inhibitory effect of aldosterone secretion by nicardipine. The unchanged PRA in SS is due to their blunted baroreflex control of heart rate. Mechanisms other than the change in the RAA system by nicardipine may account for the acute natriuretic effect. PMID- 8467313 TI - Hemodynamic effects on thrombogenesis and platelet aggregation in spontaneously hypertensive rats. AB - The present study was conducted to investigate the effect of hypertension on the formation of arterial thrombus in the rat femoral artery. The time required to establish the thrombus following endothelial injury in spontaneously hypertensive rats (SHR) was extremely prolonged. Pretreatment with prazosin which lowered the blood pressure near the level in normotensive Wistar Kyoto (WKY) rats, significantly shortened the thrombogenesis time, but it was still longer than that in WKY rats. Platelet aggregation in response to collagen with washed platelets and whole blood was reduced in SHR with and without hypotensive treatment, in comparison with that in WKY rats. Prazosin did not affect the platelet aggregability. Therefore, the decreased platelet aggregation was considered to be responsible for the delayed thrombus formation in hypotensively treated SHR. These results suggested that high blood pressure, mainly, interferes with the establishment of thrombus directly. Hypoaggregability of platelets is likely to be partly involved in the prolongation of thrombogenesis in SHR. PMID- 8467315 TI - Salivary electrolytes in treated hypertensives at low or normal sodium diet. AB - The aim of this study was to investigate possible abnormalities in salivary electrolytes in hypertensives treated with ace-inhibitors (ACE-I) or calcium antagonists (Ca-ANT) at low or normal sodium intake. Hypertensives treated with ACE-I (n.14) or Ca-ANT (n.22) and 13 normotensives were studied during normal or restricted Na intake. Na, K, Ca, Mg and Cl were determined in saliva samples collected by using a standardized adsorption procedure (SALIVETTE). Na intake was evaluated by determination of the 24-hr urinary Na excretion. Similar concentrations of Na, K, Ca, and Cl were found in normotensives and in hypertensives treated with ACEI or Ca-ANT both at low or normal Na diet. Magnesium in saliva appeared reduced in ACEI-treated hypertensives (0.28 +/- 0.06 mmol/l) in comparison to the similar values of normotensives (0.53 +/- 0.05) and Ca-ANT treated hypertensives (0.54 +/- 0.07). In normotensives and in treated hypertensives lowering of Na intake did not change the salivary content of Ca, Mg and Cl but produced in saliva a reduction of Na associated to a rise in K. Salivary Na/K ratio was significantly correlated with 24 hr urinary Na excretion in normotensives (r = 0.77; p < 0.05) and in hypertensives treated with ACE-I (r = 0.74; p < 0.05) or Ca-ANT (r = 0.62; p < 0.05). The low salivary magnesium in ACE-I-HT may have a role in the occasional ACEI-dependent dysgeusia. Salivary Na/K ratio may be used as a rough index of Na intake in treated hypertensives. PMID- 8467314 TI - Renal responses to acute volume expansion in young spontaneously hypertensive rats. AB - The renal responses to acute volume expansion (VE) were measured from intact and denervated kidneys in 5 week old spontaneously hypertensive rats (SHR). Urine flow and sodium excretion were measured before, during and after VE from innervated and denervated kidneys in anesthetized (Inactin--0.1 g/kg, ip) age and sex matched SHR and normotensive Wistar Kyoto (WKY) rats. Mean arterial pressure was 23 mm Hg higher in SHR than in WKY. During VE the increment in urinary flow rate and sodium excretion from both innervated and denervated kidneys were greater in SHR than WKY. In another group of SHR, renal perfusion pressure was maintained at a level similar to the arterial pressure in the WKY group (84 mm Hg). When renal perfusion pressure was controlled at the lower level in the SHR there was no longer the increase in diuresis and natriuresis in response to acute VE. Examining differences within a strain, the SHR demonstrate a greater increase in diuresis and natriuresis in response to VE in the absence of renal nerves, unlike the WKY. In conclusion, these results suggest that there is a greater diuresis and natriuresis in the young SHR due to increased renal perfusion pressure and the renal nerves produce a greater retention of water and sodium in SHR compared to WKY. PMID- 8467316 TI - Diuretic and natriuretic responses to ANF in the presence and absence of renal nerves in DOCA-salt hypertensive rats. AB - To determine if renal nerves contributes in the renal response to atrial natriuretic factor (ANF) in DOCA-salt hypertensive rats, diuretic and natriuretic responses to ANF were measured in Inactin (0.1 g/kg, i.p) anesthetized rats with unilateral renal denervation. Rats were assigned to either a control group (108 +/- 6 mmHg), or one of two DOCA-salt groups (injected with deoxycorticosterone acetate, DOCA, 25 mg/week, and given 0.9% saline to drink for 4 weeks); a) DOCA salt group (137 +/- 6 mmHg) and b) DOCA-salt-BPC group (with blood pressure controlled at the level of the femoral artery (102 +/- 3 mmHg) by an occluder on the abdominal aorta proximal to the right renal artery). Urine flow and sodium excretion in response to ANF infusion (0.3 micrograms/min/kg) were measured from intact and denervated kidneys of control and DOCA-salt treated rats. ANF infusion produced a significant increase in diuresis and natriuresis in all three groups of rats. Urine flow and sodium excretion in response to ANF were significantly less in the intact kidney but not the denervated kidneys of the DOCA-salt rats compared to control rats. These results indicate that renal nerves contribute to the blunted renal responses to ANF in DOCA-salt rats. Renal responses also were significantly smaller in both intact and denervated kidneys of DOCA-salt-BPC rats (in which arterial pressure was reduced) compared to DOCA-salt rats. Overall, these results indicate that both renal nerves and arterial pressure determine the natriuretic and diuretic actions of ANF in DOCA-salt hypertensive rats. PMID- 8467317 TI - Evaluation of the reproducibility and accuracy of ambulatory blood pressure monitoring using the Takeda TM-2420 automated blood pressure monitor. AB - The reproducibility of ambulatory blood pressure measurements was assessed in eight normotensive subjects who underwent three separate days of recording, using Takeda Medical TM-2420 (TM-2420) blood pressure monitors. The coefficients of variation of mean 24 hour systolic and diastolic blood pressure were 2.1% and 2.8% respectively. The corresponding values for systolic and diastolic blood pressure variability, were 19% and 14% respectively. Measurement intervals of greater than 30 minutes significantly reduced the reproducibility of mean day interval systolic measurements. The bias of the TM-2420 systolic and diastolic blood pressure measurements compared to standard sphygmomanometer measurement were 0 +/- 7 mmHg and 1 +/- 6 mmHg respectively. Ambulatory blood pressure monitoring provides reproducible estimates of mean systolic and diastolic blood pressure, however, blood pressure variability is poorly reproducible. PMID- 8467318 TI - Renin and renin inhibition in anephric man. AB - Renin activity appears to be present in low concentrations in the plasma of anephric humans but could be artifactual secondary to inadvertent activation of prorenin during specimen collection and handling or from a renin-like enzyme. We studied the effects of specimen collection, storage, different assay conditions, trypsin activation, and the renin inhibitor EMD 56133 (E Merck, Darmstadt) on plasma renin activity (PRA) in anephric man. PRA was detectable in all seven bilaterally nephrectomized (BNX) patients (0.2 +/- 0.1 ng AI/ml/hr, range 0.1 0.7) but was significantly lower than normals (2.4 +/- 0.3 ng AI/ml/hr, range 1.5 3.1, p = 0.001). PRA was not different in BNX whether blood samples were collected on ice or at room temperature and assayed immediately or whether samples were frozen and assayed several days later. Prolonged cold storage of samples and five freeze-thaw cycles over six to seven months did not significantly increase PRA in normals or anephrics. However, deliberate repeated freezing and thawing over the period of a single day increased PRA 4.1-fold in BNX and 1.6-fold in normals. Renin-like activity was also detected in BNX individuals using renin concentration determinations with either excess human or sheep angiotensinogen. The inhibition of renin activity (IC-50% = 3.16 x 10(-9) molar) by EMD 56133 was not different between BNX and normals. Thus, active renin is present in the plasma of anephric humans and does not result from the inadvertent activation of prorenin due to sample handling. Although the source of PRA in BNX is unknown, the enzyme appears functionally normal as evidenced by the dose-response to a single renin inhibitor. PMID- 8467319 TI - Central neural mechanism contributing to attenuation of angiotensin II-induced hypertension in rats on dietary calcium supplementation. AB - The effect of dietary calcium (Ca) supplementation on blood pressure (BP) and the central nervous system (CNS) mechanism underlying this effect were studied in angiotensin II (Ang II)-induced hypertensive rats. The effects of dietary Ca (0.5, 2, 4%) on systolic blood pressure (SBP), ionized Ca concentration (Ca++) in cerebrospinal fluid (CSF) and central norepinephrine (NE) turnover were investigated in male Wistar rats receiving subcutaneous infusion of Ang II (100 ng/min). Central NE turnover was studied by measuring 3-methoxy-4 hydroxyphenylglycol (MHPG) concentration in CSF with multiple electrode liquid chromatography. Ang II significantly increased SBP, and dietary Ca dose dependently attenuated the increase. SBP inversely correlated with Ca++ and MHPG in CSF. Intracerebroventricular injection of CaCl2 more markedly reduced BP in Ang II-treated rats than that in control rats. These results suggest that modulation of central NE turnover possibly caused by the increase in CNS Ca++ is involved in the anti-hypertensive mechanism of dietary Ca supplementation in Ang II-induced hypertensive rats. PMID- 8467320 TI - A renin-secreting tumour with severe hypertension and cardiovascular disease: a diagnostic and therapeutic challenge. AB - A case of renin-secreting juxtaglomerular cell tumour which presented with a severe hypertensive crisis and did not respond to angiotensin converting enzyme inhibitors but was promptly controlled by intravenous labetalol is reported. The diagnostic difficulties which can be encountered in such cases and the usefulness of the different diagnostic tests, including renal vein renin measurement, are discussed. PMID- 8467321 TI - Atrial natriuretic factor response to acute volume expansion in borderline hypertension. Role of ACE-inhibition and changes in peripheral venous tone. AB - Abnormalities in the response of atrial natriuretic factor (ANF) to volume expansion have been reported in hypertensive-prone animals and men as well as in hypertensive patients undergoing ACE-inhibition. To investigate some of the mechanisms affecting ANF release in borderline hypertensive patients (BHT) we have studied 16 subjects by assessing their neuro-humoral and hemodynamic response to a two-hour isotonic i.v. NaCl infusion carried out during short-term administration of either placebo or captopril. ACE-inhibition increased baseline venous distensibility (VV30:1.4 vs 1.6 ml/100 ml; p < .05) and reduced the prompt (45') ANF response to saline loading (10.3 +/- 13 vs 42.7 +/- 15%; p < .05)) without affecting the overall ANF release (120':92 +/- 25 vs 65.8 +/- 20%; NS)). A significant pressor increase in response to NaCl loading was observed exclusively after ACE-inhibition (SBP: 5.2 +/- 2 vs 2.4 +/- 1%; p < .05--DBP: 7.1 +/- 3 vs 2 +/- 3%; p < .025) and occurred along with a peripheral arterial and venous constriction and with an increase in plasma levels of an endogeneous Na+/K+ATPase inhibitor (8.8 +/- 4 vs -2 +/- 4%; p < .05). We conclude that the ANF response to saline infusion is delayed by ACE-inhibition in borderline hypertensives. The abnormalities observed in ANF response could follow the changes in peripheral venous distensibility and contribute to the pressor and neuro-humoral derangements described in borderline hypertensives during volume expansion. PMID- 8467322 TI - Arterial pressure, plasma renin activity, atrial natriuretic factor, and sodium excretion during induced hyper- and hypoinsulinemia in therapy-resistant hypertensives. AB - We investigated whether short-term changes in serum insulin would effect a reduction of arterial pressure in subjects with therapy-resistant essential hypertension. Six patients were examined twice with a 3 week's interval in a single-blind cross-over design with euglycemic insulin clamps (A and B). A reduction of endogenous serum insulin was achieved by continuous infusion of 50 microgram octreoid (a somatostatin analogue) per hour. During clamp A low dose insulin infusion (5 mU/m2/min) was given, whereas during clamp B insulin was infused at a rate of 60 mU/m2/min. Preceding each clamp a standard drug therapy was given for one week (50 mg atenolol+ 30 mg furosemide per day). During clamp A plasma insulin was reduced from 21.4 +/- 7.5 to 10.8 +/- 1.2 mU/l (p < 0.01) whereas plasma insulin rose during clamp B from 20.0 +/- 7.5 to 99.0 +/- 17.2 mU/l (p < 0.001). The mean arterial blood pressure did not decrease during clamp A (low dose insulin infusion). There was an increased natriuresis during the high insulin clamp (70 vs. 38 mmol, p = 0.13), but no difference in arterial pressure between the clamps. The results do not support the notion that high insulin levels contribute to hypertension in therapy resistant hypertensive patients by any direct and immediate mechanism. PMID- 8467323 TI - Heritability estimates of blood pressure in genetically selected White Carneau pigeons. AB - Seven White Carneau (WC) pigeon families of the high blood pressure (HBP) line with 51 offspring and six families of the low blood pressure (LBP) line with 57 offspring were used to estimate heritability of the blood pressure trait. Pigeons from the HBP line had significantly higher systolic blood pressures than the LBP line at ages 1 through 6 months. No significant effect of age on blood pressure was observed in either the HBP line or the LBP line. Systolic, diastolic and mean arterial pressures were 155 +/- 6.4 and 122 +/- 5.7 and 139 +/- 6.1, respectively, for male parents and 163 +/- 9.3 and 125 +/- 7.1 and 143 +/- 8.3, respectively for female parents. The mid-parent mean averaged across pairs was 159 +/- 7.3 and 123 +/- 5.9, and 141 +/- 6.6, for systolic, diastolic, and mean arterial pressures, respectively. The average systolic, diastolic, and mean arterial pressures for offspring were 159 +/- 5.9, 132 +/- 5.5, and 147 +/- 5.6, respectively. Blood pressure measurements did not differ greatly between the offspring and the mid-parent mean, indicating that offspring inherit blood pressure levels similar to those of their parents. Mean heart rates were 189 +/- 12.2, 202 +/- 14.2 and 197 +/- 9.9 for the male parents, female parents and offspring, respectively. Heritability estimated by the regression of offspring on the mid-parent mean was 0.55 +/- 0.18, 0.69 +/- 0.19 and 0.61 +/- 0.18, 0.82 +/- 0.19 for systolic, diastolic and mean arterial pressure and heart rate, respectively. The results suggest that genetic factors play a significant role in influencing blood pressure in WC pigeons. PMID- 8467325 TI - Effects of nisoldipine on hypertension and glomerulosclerosis in Cohen diabetic rat with Goldblatt hypertension. AB - Nisoldipine treatment for five months prevented a rise in blood pressure in Cohen diabetic rats with Goldblatt hypertension, compared to a significant elevation in untreated controls. Blood creatinine and urea also decreased significantly in the treated animals, and renal lesions were less severe. The prevalence of glomerulosclerosis, however, remained unaltered in both the treated and control groups. These findings indicate that increased blood pressure aggravates renal changes, while reducing it eliminates the aggravation. PMID- 8467324 TI - Atrial natriuretic factor and changes in the aldosterone response to angiotensin II in sodium depleted dogs. AB - The effects of physiological shifts in plasma atrial natriuretic factor (ANF) concentrations on angiotensin II/aldosterone relationships during changes in sodium status were assessed in 6 conscious beagle dogs. Incremental infusions of angiotensin II (3, 9 and 27ng/kg/min) were administered on three occasions. The animals were studied in sodium replete and deplete states and on a third occasion, again while sodium deplete, with a background constant low-dose infusion of ANF (1.5pmol/kg/min) sufficient to enhance the low endogenous plasma ANF values observed in sodium depletion to match those observed in the sodium replete state. Sodium depletion caused a leftward shift and steepened the slope of the relationship between achieved arterial angiotensin II concentrations and the plasma aldosterone response. This effect was significantly attenuated (approximately 50%) by the low dose ANF infusions which tended to flatten the slope of the angiotensin II/aldosterone curve (ns) and shifted it significantly to the right (p < 0.05). These data suggest subtle shifts in endogenous levels of plasma ANF, accompanying changes in sodium status, are a major contributor to the associated alterations in angiotensin II/aldosterone relationships. Low dose ANF also significantly reduced the effect of angiotensin II on arterial pressures but did not alter natriuresis. PMID- 8467326 TI - Muscarinic receptors in the aortae of normo- and hypertensive rats: a binding study. AB - The muscarinic receptors in the aorta of the normo- and hypertensive rats were characterised with tritiated acetylcholine (3H-ACh) and various muscarinic receptor antagonists. The binding of 3H-ACh to the endothelial membranes of the normotensive Wistar Kyoto rats (WKY) and the spontaneously hypertensive rats (SHR) was displaceable by nanomolar range of scopolamine but only by micromolar range of atropine and homatropine. The reverse was observed with the muscle binding sites, i.e. the 3H-ACh was displaceable by nanomolar range of atropine and homatropine but only by micromolar range of scopolamine. Pirenzepine and 4 diphenyl-acetoxy-N-methyl-piperidine metobromide (4-DAMP) displaced the binding of 3H-ACh from both tissues in the nano to micromolar range, with the displacement from the endothelial binding sites occurring at lower concentration range of the ligands. The apparent IC50 values of both compounds for the smooth muscle were 9 and 16 times greater than those for the endothelial binding sites respectively. When saturated with guanylyl-imididiphosphate (GppNHp), conversion of high to low-affinity binding site occurred in both tissues of the WKY but only in the smooth muscle of the SHR. GppNHp had no apparent effect on the binding of 3H-ACh to the endothelial binding sites confirming that the high-affinity site for 3H-ACh was missing in the endothelium of the SHR. PMID- 8467327 TI - The effects of PEG-interleukin-2 and interleukin-2 on essential hypertension and cellular immune function in the spontaneously hypertensive rat. AB - The effects of recombinant human interleukin-2 covalently linked to polyethylene glycol (PEG-IL-2) or interleukin-2 (IL-2) on hypertension and in vitro suppressor T cell function in the spontaneously hypertensive rats (SHR) were investigated. Male young prehypertensive (4 weeks old) SHRs and adult (10 weeks old) SHRs with established hypertension were injected with low (5,000 units (u)/kg) or high (50,000-100,000 u/kg) dose of PEG-IL-2 or IL-2 as a single bolus or repeated injections. Systolic blood pressure was measured twice weekly using the tail-cuff technique. Systolic blood pressure in the PEG-IL-2 or IL-2 treated animals, irrespective of age, dose, or route of injection, did not differ significantly from that measured in vehicle-treated controls over a 10 week period. Mean arterial pressure measured by intra-arterial catheter was 159 +/- 7 mm Hg 10 weeks after treatment with repeated injections of 5,000 u/kg of PEG-IL-2 and 158 +/- 9 mm Hg in vehicle-treated controls. All rats injected with IL-2 had IL-2 specific IgG antibody in their sera. None of the PEG-IL-2 treated rats had any detectable anti-IL-2 antibodies in their sera. Thus, PEG-IL-2 showed far less immunogenicity than IL-2. Suppressor T (Ts) cells generated from adult SHR spleen cells failed to suppress pokeweed mitogen (PWM)-driven immunoglobulin G (IgG) synthesis. PEG-IL-2 or IL-2 supplementation both in vitro and in vivo restored the ability of adult SHR to generate Ts cells able to inhibit IgG synthesis. Our data suggest that PEG-IL-2 or IL-2 administration does correct a prominent defective Ts cell activity found in adult SHR, but that correction of this immune abnormality is not attended by an attenuation of hypertension. PMID- 8467328 TI - The effects of imagery on emotions, immune function, and cancer outcome. PMID- 8467329 TI - Responses of existing women's organizations to the women's movement of the 1970s- competition or cooperation. PMID- 8467330 TI - The relationship between quadriceps angle and anterior knee pain syndrome. AB - Anterior knee pain syndrome (AKPS) represents a significant challenge for patients and for clinicians. The purposes of this study were: 1) to determine the reliability of the Q-angle measurement, 2) to quantify Q-angle changes that occur with knee flexion, and 3) to determine if subjects with AKPS (N = 52) have a significantly different Q-angle than subjects without AKPS (N = 50). With the knee in an extended position, intratester Q-angle intraclass correlation coefficients (ICC) ranged from .84 to .90, and standard error of measurement (SEM) values ranged from 2.01 to 2.23 degrees. Intertester Q-angle ICC was .83, and the SEM was 2.49 degrees. With the knee flexed, the intratester ICC was .83 for both testers, and SEM values ranged from 0.68 to 2.45 degrees. Intertester ICC and SEM were .65 and 3.50 degrees, respectively. No significant difference was found in intratester Q-angle values between the extended and flexed knee positions (p > 0.05). No significant difference in Q-angle was found between asymptomatic subjects (11.1 +/- 5.5 degrees) and symptomatic subjects (12.4 +/- 5.1 degrees) (p = 0.07). Increased Q-angles were not responsible for AKPS in this group of patients. Other factors were hypothesized to be responsible for their symptoms. PMID- 8467331 TI - The stretch-shortening cycle of the quadriceps femoris muscle group measured by isokinetic dynamometry. AB - The ability to measure the stretch-shortening cycle of isolated muscle groups has been limited. The purpose of this study was to measure the stretch-shortening cycle of the quadriceps femoris muscle group. Twenty-four volunteer subjects, 12 men and 12 women, participated in one test session; five men and five women also participated in a retest session; to examine the reliability of the test. A concentric contraction of the left quadriceps was measured for peak torque and time to peak torque on a Biodex isokinetic dynamometer under three conditions: 1) passive stretch before a concentric contraction, 2) isometric preload before a concentric contraction, and 3) eccentric preload before a concentric contraction. Conditions 2 and 3 showed a significant increase in peak torque production compared to condition 1 (p < 0.01). A significant difference was found for all three conditions between the men and women, with the men producing greatest peak torques. Conditions 2 and 3 also showed a significantly decreased time to peak torque compared with condition 1 (p < 0.01). The testing protocol was found to have high reliability. This testing protocol could be used to further study the stretch-shortening cycle in the quadriceps femoris muscle group. PMID- 8467332 TI - The effect of foot orthotics and gait velocity on lower limb kinematics and temporal events of stance. AB - Research on foot orthotics is primarily restricted to their effect on the lower limb during running. Research is limited, however, on the potential of foot orthotics to control the mechanics of the foot during walking. The purpose of this study was to examine the interactive effect of foot orthotics and two walking speeds on the angular changes at the rearfoot, ankle, and knee, and temporal events during stance. Ten subjects demonstrating a minimum of 3 degrees of calcaneal eversion in relaxed standing participated in the project. All subjects routinely wore functional orthotics that were used during testing in conjunction with personal athletic shoes. Individuals were tested with and without the orthotics while walking on a treadmill at 2 and 3 mph. A four-camera motion analysis system was used to capture three-dimensional motion at 60 frames per second. Angle plots illustrated changes in joint motion at the knee, ankle, and rearfoot. Temporal data for heel strike, heel rise, and toe off of the foot during the stance were calculated. A two-factor repeated analysis of variance was used to determine the main and interactive effects of the orthotic and speed on the dependent variables. When walking with the orthotic, there was a significant reduction in the degree of pronation throughout stance as well as an increase in the duration of stance time as measured from heel strike to heel rise. The orthotic did not significantly reduce the velocity of pronation during the first 20% of stance. There was a speed effect for peak dorsiflexion and knee flexion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467333 TI - The effects of pad placement and angular velocity on tibial displacement during isokinetic exercise. AB - The purpose of this study was to compare the effects of proximal single resistance pad placement (PSPP) and distal single pad placement (DSPP) on tibial displacement during isokinetic exercise on anterior cruciate ligament (ACL) deficient knees. This study is important to the clinician because it documents tibial displacement during open chain isokinetic knee extension exercise at various isokinetic speeds. In addition, this study documents the range of motion where the greatest amount of anterior tibial displacement occurs. The anterior displacement of the tibia was recorded by a computerized knee laxity testing device during isokinetic exercise. Data were collected from 12 ACL-deficient knees. Each subject was tested on an OSI Knee Signature System for quantifiable tibial displacement during a Lachman's test, anterior drawer test, and active vs. passive knee extension. Following this, each subject was tested on a Biodex isokinetic dynamometer at isokinetic velocities of 60, 180, and 300 degrees/sec with the computerized knee laxity testing device in place. Pad placement consisted of distal single pad placement, which is 1 inch proximal to the medial malleolus, and proximal single pad placement, which is 3 inches proximal to the DSPP location. The testing procedure was standardized, and peak torque was monitored to ensure consistent maximal effort throughout the study. The results indicated that PSPP resulted in less anterior tibial displacement at all three test speeds. The peak anterior tibial displacement occurred in a range from 30 to 15 degrees of knee flexion at both pad placements and all three test speeds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467334 TI - The effect of isokinetic exercise on the relationship between blood lactate and muscle fatigue. AB - Exercise velocity may be an important variable in determining the amount of blood lactate accumulation during isokinetic exercise. The purpose of this study was to measure the effects of velocity-specific isokinetic exercise on blood lactate, muscle fatigue index, and rating of perceived exertion and to examine the relationship between blood lactate and muscle fatigue index. Ten experienced recreational weight trainers, aged 20-40 years, took part in a repeated measures design consisting of three separate treatments (constant angular velocity at 30, 120, and 300 degrees/sec performed at maximal effort for 1 minute by the right knee flexors and extensors). Rating of perceived exertion, blood lactate, and muscle fatigue index were measured in response to each treatment. Rating of perceived exertion was equal across all three speeds. Muscle fatigue and blood lactate increased significantly as the velocity of exercise increased. There was also a positive correlation coefficient (r = .82, < or = 0.01) between muscle fatigue index and blood lactate. The data suggested that the magnitude of muscle fatigue index and blood lactate responses are strongly dependent on the velocity of movement utilized during maximal isokinetic exercise, and there is a relationship between muscle fatigue index and blood lactate. PMID- 8467335 TI - Athletic trainer utilization in sports medicine clinics. AB - Increased use of athletic trainers in sports medicine clinics has created a need for information related to actual and ideal use of these professionals in these settings. The purposes of this study were to 1) describe the characteristics of sports medicine clinics and their personnel, 2) determine whether there were differences between opinions of certified athletic trainers (ATCs), physical therapists (PTs), and professionals with dual credentials (PT/ATCs) about the ideal role of the ATC in sports medicine clinics, and 3) determine whether there were differences in actual usage of ATCs between states with and without athletic training laws. Subjects included 46 PTs, 43 PT/ATCs, and 73 ATCs from six different states. A questionnaire ascertained opinions about ideal ATC utilization and about current practice of ATCs with respect to 28 different clinical procedures. For 27 of the 28 procedures, there were significant differences of opinion about ideal ATC utilization between individuals with the three credentials. No significant differences in actual athletic trainer use in sports medicine clinics were found between states with and without athletic training laws. PMID- 8467337 TI - Mechanical power and muscle action during forward and backward running. AB - Recently, there has been increasing interest in using backward running (BR) as an exercise and rehabilitation tool. To date, no study has been performed that combined electromyography (EMG) and joint kinetics to study BR. The purpose of this study was to compare selected EMG and kinetic parameters in the stance phase of forward running (FR) and backward running (BR). The sagittal plane of the right knee was analyzed during three trials of FR and BR in six male subjects. Four 60-Hz video cameras collected motion data, and a link segment model of the right lower extremity was established. Force plate and EMG data were collected at 1000 Hz and synchronized with the video data. The knee muscle peak (+) and peak ( ) mechanical power and total (+) and total (-) mechanical work were calculated. Electromyography signals were captured from the right lower extremity on the rectus femoris, vastus lateralis, vastus medialis, biceps femoris, gastrocnemius, and tibialis anterior muscles. Statistical analysis indicated that significantly less (p < 0.05) peak (+) and (-) power and total (+) work occurred at the knee during BR than during FR. Significant differences (p < .05) in muscle firing patterns between conditions were observed. Muscle action of the vastus lateralis (VL) and vastus medialis oblique (VMO) was largely eccentric and concentric during FR and isometric and concentric during BR. Backward running appears to be a good method for achieving isometric and concentric muscle action of the VMO and VL and may be useful in clinical conditions that require an increase in knee extensor strength. PMID- 8467336 TI - Lower extremity muscular flexibility in long distance runners. AB - Muscle tightness is often considered to be a predisposing factor in muscle injuries. The purpose of this study was to assess the muscle flexibility of the hamstrings, rectus femoris, iliopsoas, gastrocnemius, and soleus muscles in long distance runners. Range of motion measurements of five movements, including hip flexion with knee extended, hip extension with knee flexed, hip extension with knee extended, ankle dorsiflexion with knee extended, and ankle dorsiflexion with knee flexed, were evaluated to determine muscle tightness. Twenty runners and 20 nonrunners volunteered for the study. Each group consisted of 10 males and 10 females. The observed means were compared between runners and nonrunners, males and females, plus the dominant and nondominant leg using a three-way analysis of variance. The runners were found to have tighter hamstrings (p < .05), and soleus (p < .05) muscles than nonrunners. There was no significant difference in rectus femoris and iliopsoas muscle tightness in runners compared with nonrunners. In addition, the males had tighter hamstring muscles than the females in both runners and nonrunners (p < .05). The hamstring muscles of the dominant leg were tighter than the hamstrings of the nondominant leg in all subjects (p < .05). In conclusion, long distance runners appear to have posterior muscle tightness in the lower extremity. PMID- 8467338 TI - Development of a computer-assisted method for the collection, organization, and use of patient health history information in physical therapy. AB - Screening a patient's general health prior to instituting physical therapy management is generally acknowledged as important. However, neither the specific content nor the optimal method of performing this part of patient examination has received much attention. One method that uses a computerized information management system to assemble relevant clinical literature and to guide the collection, organization, and use of patient health history data in clinical decision-making is described. The philosophy and rationale for performance of general health screenings by physical therapists, justification for the use of computers in the screening process, and the development and application of one type of computer-assisted health history screening system for physical therapy are presented. PMID- 8467339 TI - Performing arts medicine: the musical athlete. AB - Musicians and dancers in the performing arts place abnormal stresses on their musculoskeletal systems, resulting in overuse injuries. The purpose of this paper is to address the factors contributing to musculoskeletal injuries sustained by musicians. Recommendations for evaluative procedures, treatment, and education in dealing with the needs of this population are discussed. PMID- 8467340 TI - The effects of immediate continuous passive motion on pain during the inflammatory phase of soft tissue healing following anterior cruciate ligament reconstruction. AB - Continuous passive motion (CPM) may have potential application as a physical modality in decreasing acute pain. The purpose of this study was to examine the effects of CPM immediately following an arthroscopically-assisted anterior cruciate ligament (ACL) reconstruction utilizing bone-patella-bone autograft on acute pain during the inflammatory phase of soft tissue healing. Acute pain was measured by assessing the amount of pain medication (amount of narcotic delivered from the patient-controlled analgesia (PCA) pump during the first postoperative 24 hours and the total intake of oral medication during the second and third postoperative days), the need for pain medication (number of times the patient pushed the PCA button during the first postoperative 24 hours), and perceived pain (graphic pain scale measuring antalgic sensation). Thirty patients (15-45 years old) participated in this study. The patients were prospectively randomized into two groups, CPM and non-CPM. Both groups followed an identical postoperative rehabilitation program except for the CPM groups using a CPM device. The design of this study included the collection of data during the inflammatory phase of soft tissue healing. The results indicated that the initiation of CPM immediately following an ACL reconstruction had a significant (p < .05) effect on decreasing the amount of medication consumed by the patient and a significant (p < .05) decrease in the patient's need for medication during the inflammatory phase. There was no statistical significance in the level of perceived pain between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467341 TI - A comparison of two different methods to treat hip pain in runners. AB - Little or no research has been performed on the physical therapy treatment of hip pain. The purpose of this study was to compare two different treatments for hip pain. Twenty runners who had primary hip pain and sacroiliac joint dysfunction, without evidence of arthritic changes, were randomly assigned to two groups. One group received a mobilization technique to the involved hip, while the other was treated with a manipulative technique known to affect sacroiliac joint dysfunction. The subjects were evaluated by using a pain questionnaire and the Faber test to determine the response of the hip joint to treatment. Data were analyzed with the Mann-Whitney U statistic for perceived pain response and with the Chi-square statistic with Yates correction for the Faber test. Results showed a significant difference in perceived pain response, as well as reproduction of pain with the Faber test, between the two groups. The results suggest that a manipulative technique designed to reduce sacroiliac joint dysfunction is an effective method to reduce hip pain. Physical therapists should evaluate the sacroiliac joint in patients with hip pain. PMID- 8467342 TI - Effects of electrical and electromagnetic stimulation after anterior cruciate ligament reconstruction. AB - A need exists to develop new methods of neuromuscular electrical stimulation (NMES) that are both effective and relatively pain-free. The purpose of this pilot study was to determine the effects of both NMES and a new method of electromagnetic (NMES/PEMF) stimulation for reducing girth loss and for reducing pain and muscle weakness of the knee extensor muscles in patients during the first 6 weeks after reconstructive surgery of the anterior cruciate ligament (ACL). Seventeen patients receiving ACL reconstructive surgery participated as a control group (N = 3), as an NMES group (N = 7), and with combined NMES and magnetic field stimulation (NMES/PEMF) (N = 7). Patients receiving NMES/PEMF rated each type of stimulation for perceived pain and were measured for their torque. Torque results revealed a mean decrease of 13.1% for NMES/PEMF patients. The mean percent of thigh girth decreased 8.3% for controls, 0.5% for NMES, and 2.3% for NMES/PEMF patients. The NMES/PEMF patients rated NMES as causing about twice the pain intensity as NMES/PEMF during treatments. As a result of this data, the authors conclude that both NMES and NMES/PEMF are effective in reducing girth loss and that NMES/PEMF is less painful than NMES alone in treating patients after ACL reconstruction. PMID- 8467343 TI - Clinical evaluation of the BackMate lower lumbar rehabilitation system: results of a preliminary study. AB - Back pain profoundly affects daily activities and quality-of-life parameters. It was the intent of the present study to evaluate a procedure of stretching and strengthening the lower back musculature with the aid of a pelvic stabilization device, the BackMate, for the treatment of lower back pain. Subjects suffering from chronic back pain (> 3 months in duration) were studied. The treatment program consisted of three therapy sessions per week for 3 weeks. Sitting time, walking distance, and lower back pain, parameters reported by the subjects, significantly improved regardless of age and sex of the subjects. Similarly, objective parameters, including forward bend, straight leg raise, and hamstring flexibility, significantly improved. This preliminary experience suggests that stretching and strengthening procedures performed with the aid of a pelvic stabilization device may prove to be a significant addition to current clinical treatment procedures for lower back pain. PMID- 8467344 TI - Retro runner with ischial tuberosity enthesopathy. AB - In reviewing the literature, no studies were found reporting the use of retro running on flat and hilly terrain, which elicited enthesopathy (stress reaction) at the ischial tuberosity. Therefore, this case study of an atypical enthesopathy condition warrants careful scrutiny in order to generate future research. This case study describes the clinical management of a female runner with bilateral patellofemoral pain who self-initiated a program of backward running and stationary bicycling after reading an article about retro running in a runners' magazine. She subsequently developed ischial tuberosity enthesopathy verified by scintigraphy (bone scan). Her symptoms gradually resolved with physical therapy intervention. Eventually, she was able to forward jog 2 miles on flat surfaces without complaint of pain but did not resume retro running. This case not only suggests the need for further research in retro running kinetics and kinematics but highlights the proactive role health professionals must assume in injury prevention. PMID- 8467345 TI - HDL-cholesterol: exercise formula. Results of long-term (6-year) strenuous swimming exercise in a middle-aged male with paraplegia. AB - Paraplegic individuals are at increased risk for developing heart disease because of low HDL-cholesterol levels. Exercise has been identified as an important factor in raising the HDL-cholesterol level. This case study documents the effects of long-term (6-year) strenuous exercise (2940 kcal/wk) on lipid markers in a 41-year-old white male with paraplegia. An additional 21 mg of HDL cholesterol (84% increase) were observed in a paraplegic individual who swam 2100 kcal/week for 6 years. Througout this study, serial blood samples were analyzed for total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. An initial low HDL-cholesterol of 25 mg/dl was measured in the subject. This case study continued for 72 months to determine the long-term effects on various blood lipid fractions of swimming an additional 2.5 hours/week. HDL-cholesterol slowly increased over the duration of the study. After 12 months of swimming the HDL fraction had increased from 25 mg/dl to 31 mg/dl. After 24 months and at the end of 72 months of swimming, the HDL fraction had risen to 43 mg/dl and 46 mg/dl, respectively. The estimated long-term energy cost for each additional 1 mg/dl of HDL-cholesterol above the pre-exercise HDL value was 100 kcal/week in this subject. Long-term strenuous swimming exercise has been successfully incorporated into the lifestyle of a paraplegic individual. Significant reduction in known coronary risk factors followed a marked increase in the HDL-cholesterol level. PMID- 8467346 TI - Physiopharmacological interactions between stress hormones and central serotonergic systems. AB - The present review tries to delineate some mechanisms through which the sympathetic nervous system (SNS) and the hypothalamo-pituitary-adrenal (HPA) interact with central serotonergic systems. The recent progress in 5 hydroxytryptamine (5-HT) receptor pharmacology has helped to define the means by which central serotonergic activity may alter the respective activities of the SNS (sympathetic nerves and adrenomedulla) and of the HPA axis. These pharmacological findings have also helped to characterize the differential effects of central 5-HT upon different branches of the SNS and the numerous sites at which 5-HT exerts stimulatory influences upon the HPA axis. Although relevant to stress-related neuroendocrinology, the extent to which these interactions are involved in the antidepressant/anxiolytic properties of some serotonergic agents still remains to be clarified. Beside these findings, there is also abundant evidence for a tight control of central serotonergic systems by stress hormones. Activation of the SNS increases, by numerous means, central availability of tryptophan, whereas glucocorticoids exert differential actions upon the intra- and the extraneuronal regulation of 5-HT function. Actually, a significant number of these mechanisms is involved in the maintenance of homeostasis during stressful events, thereby conferring to these mechanisms a key role in adaptation processes. PMID- 8467347 TI - Long-term potentiation as synaptic dialogue. AB - We have proposed a testable model of the physiological and biochemical events underlying LTP that offers the following novel features. (1) The focus is not on a single mechanism or synaptic site, but rather on the integration and interaction of mechanisms occurring on both sides of the synapse, (2) beta PKC plays a critical presynaptic role in LTP, while gamma PKC functions postsynaptically. (3) These stages can be ordered in a time-delimited sequence of post- then presynaptic molecular events based on the period of effectiveness of inhibitor compounds. (4) The distinction is made between the time when kinase activation occurs and the time when the potentiated response requiring this kinase activation is observed. PMID- 8467348 TI - Ascorbic acid in the brain. AB - Ascorbic acid is highly concentrated in the central nervous system. Measurement of the extracellular concentration of ascorbate in animals, mainly by the technique of voltammetry in vivo, has demonstrated fluctuation in release from neuropil, both spontaneously and in response to physical stimulation of the animal and to certain drugs. Although in the adrenal medulla ascorbate is co released with catecholamines, release of ascorbate from brain cells is associated principally with the activity of glutamatergic neurones, mainly by glutamate ascorbate heteroexchange across cell membranes of neurones or glia. This phenomenon is discussed in relation to a possible role of ascorbate as a neuromodulator or neuroprotective agent in the brain. PMID- 8467349 TI - The neuropharmacological and neurochemical basis of place learning in the Morris water maze. AB - The Morris water maze (MWM) offers several advantages over other methods of studying the neurochemical basis of learning and memory, particularly with respect to its ability to dissociate deficits in memory formation from deficits in sensory, motor, motivational and retrieval processes. The contributions of nearly all of the major neurotransmitter systems have been investigated and consistent patterns have emerged. Normal function in glutamatergic and cholinergic systems is necessary for spatial learning, as blockade of NMDA receptors and cholinergic hypofunction prevents spatial learning but does not impair recall. Peptides such as adrenal and sex hormones and somatostatin may also be necessary for spatial learning. In contrast, activity in either GABAergic or opioidergic systems impairs spatial learning, though by quite different means. GABAergic activity prevents memory function, whereas opioidergic activity reduces motivation. Normal monoaminergic activity is necessary for normal performance in the MWM, but not for spatial learning per se. However, noradrenergic and serotonergic systems may enhance cholinergic-mediated mnemonic processes. Further research into the relative contributions of different receptor subtypes as well as interactions between neurochemical systems should provide significant advances in our understanding of the neural basis of learning and memory in mammals. PMID- 8467350 TI - Sexual dimorphism in the vomeronasal pathway and sex differences in reproductive behaviors. AB - Several years ago we hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. This hypothesis sprung from several facts; (a) the existence of steroid receptors in the VNS; (b) sexual dimorphism was already described in some structures that receive vomeronasal input, such as the medial preoptic area, the ventromedial hypothalamic nucleus, the ventral region of the premammillary nucleus and the medial amygdaloid nucleus; and (c) the vomeronasal organ, which is the receptor organ of the VNS, was also sexually dimorphic. After that point, the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT) and the bed nucleus of the stria terminalis were found to be sexually dimorphic. The aim of the present review is to show the experimental facts that confirm our earlier hypothesis and, consequently, to present the existence of a sexually dimorphic multisynaptic pathway for the first time in mammals. Sexual dimorphism in the VNS might provide a comprehensive approach to understanding the neural bases of sexually dimorphic reproductive behavior and it is suggested here that the greater number of neurons which male rats present in relation to females in most VNS structures might contribute to the inhibition of the expression of feminine copulatory behavior (lordosis) and maternal behavior in males. In addition, the mechanisms that control the development of sexual dimorphism in the VNS are discussed. The discussion takes into account the two patterns of sexual dimorphism found in the rat brain. Estrogens seem to promote the development of sexual dimorphism in both male and female rats. However, an inhibitory role of androgens might be necessary to hypothesize when males or females present a lower number of neurons and/or volume than the opposite sex. There are experimental data supporting this hypothesis in the female, since dihydrotestosterone seems to facilitate neuronal death in VNS structures, such as the AOB and the BAOT, in which females present a lower number of neurons and volume than male rats. Finally, since the lateral division of the bed nucleus of the stria terminalis, which belongs to the main olfactory system (MOS), is sexually dimorphic and presents anatomical relationships with some VNS structures the MOS might be sexually dimorphic. PMID- 8467351 TI - Possible action of cyclopiazonic acid on myocardial sarcoplasmic reticulum: inotropic effects on neonatal and adult rat heart. AB - Cyclopiazonic acid (CPA), a mycotoxin from Aspergillus and Penicillium, has been described as a highly selective inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum (SR) in skeletal and smooth muscles but no reports at present deal with the effect of CPA in cardiac muscle. In the present study, we examined the inotropic effect of CPA on adult and neonatal rat myocardia, the contractions of which are known to be highly dependent on Ca(2+)-release from the sarcoplasmic reticulum and transsarcolemmal Ca(2+)-influx, respectively. CPA (30 microM) produced a negative inotropic effect in adult preparations, accompanied by marked prolongation of the contraction duration. In contrast, CPA had minimum effects on neonatal myocardium. Thus we have demonstrated that CPA exerts negative inotropic effects on adult myocardium probably through inhibition of SR function. PMID- 8467352 TI - Anti-inflammatory actions of an N-terminal peptide from human lipocortin 1. AB - An acetylated polypeptide corresponding to residues 2-26 of human lipocortin 1 was synthesized and the anti-inflammatory activity assessed in three models of acute inflammation in rat and mouse. In the carrageenin rat paw oedema test, the peptide produced a maximal inhibition of approximately 41% at the 3 h time point with a 10 micrograms dose. When rat paw oedema was induced by the injection of venom phospholipase A2, the peptide produced a significant inhibition (31%) at the top dose of 20 micrograms per paw. In the mouse air-pouch model, systemic treatment with the peptide produced a dramatic reduction in cytokine-induced leukocyte migration with an ID50 of approximately 40 micrograms per mouse. The N terminal peptide 2-26 shares the actions of lipocortin 1 in these acute models of inflammation. PMID- 8467353 TI - Active secretion of the fluoroquinolone ciprofloxacin by human intestinal epithelial Caco-2 cell layers. AB - The bidirectional transepithelial fluxes of ciprofloxacin, an antibacterial fluoroquinolone, across the human intestinal epithelial Caco-2 cell-line show marked asymmetry. Basal-to-apical flux of ciprofloxacin (10 microM) exceeds apical-to-basal flux indicating net secretion. Net ciprofloxacin secretion is abolished by azide/2-deoxy-D-glucose treatment, displays saturation kinetics (Km = 0.89 +/- 0.23 mM, Vmax 44.3 +/- 4.9 nmol cm-2.h) and competition by other fluoroquinolones. A specific, active secretion in Caco-2 epithelia may explain the transintestinal elimination of ciprofloxacin observed in pharmacokinetic studies in man. PMID- 8467354 TI - Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine. AB - 1. Administration to rats of methamphetamine (15 mg kg-1, i.p.) every 2 h to a total of 4 doses resulted in a neurotoxic loss of striatal dopamine of 36% and of 5-hydroxytryptamine (5-HT) in the cortex (43%) and hippocampus (47%) 3 days later. 2. Administration of chlormethiazole (50 mg kg-1, i.p.) 15 min before each dose of methamphetamine provided complete protection against the neurotoxic loss of monoamines while administration of dizocilpine (1 mg kg-1, i.p.) using the same dose schedule provided substantial protection. 3. Measurement of dopamine release in the striatum by in vivo microdialysis revealed that methamphetamine produced an approximate 7000% increase in dopamine release after the first injection. The enhanced release response was somewhat diminished after the third injection but still around 4000% above baseline. Dizocilpine (1 mg kg-1, i.p.) did not alter this response but chlormethiazole (50 mg kg-1, i.p.) attenuated the methamphetamine-induced release by approximately 40%. 4. Dizocilpine pretreatment did not influence the decrease in the dialysate concentration of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) produced by administration of methamphetamine while chlormethiazole pretreatment decreased the dialysate concentration of these metabolites still further. 5. The concentration of dopamine in the dialysate during basal conditions increased modestly during the course of the experiment. This increase did not occur in chlormethiazole-treated rats. HVA concentrations were unaltered by chlormethiazole administration. 6. Chlormethiazole (100-1000 microM) did not alter methamphetamine (100 microM) or K+ (35 mM)-evoked release of endogenous dopamine from striatal prisms in vitro. 7. Several NMDA antagonists prevent methamphetamine-induced neurotoxicity; however chlormethiazole is not an NMDA antagonist. Inhibition of striatal dopamine function prevents methamphetamine induced toxicity of both dopamine and 5-HT pathways. Therefore the attenuation of the enhanced dopamine release which occurs in animals given chlormethiazole may be associated with the protective action of this drug against methamphetamine induced neurotoxicity. PMID- 8467355 TI - Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors. AB - 1. The 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) has been evaluated in a mouse model for detecting potential antidepressants (Porsolt test). The effects of various receptor antagonists, lesions of brain monoaminergic neurones and chronic drug treatments on this 8-OH DPAT-induced response have also been determined. 2. 8-OH-DPAT (0.3-10.0 mg kg-1, s.c.) dose-dependently increased the mobility of mice in the Porsolt test. Other selective 5-HT1A receptor ligands (0.3-30 mg kg-1, s.c.) either mimicked the 8-OH DPAT response (ipsapirone, at 10 and 30 mg kg-1, s.c.) or were inactive (buspirone and gepirone). However, each of these compounds (< or = 100 mg kg-1, p.o.) inhibited the response to 8-OH-DPAT (3 mg kg-1, s.c.) when given concurrently. 3. The putative 5-HT1A antagonists, spiroxatrine (1-30 mg kg-1, p.o.), (+/-)-pindolol (30 mg kg-1, p.o.) and methiothepin (3-10 mg kg-1, p.o.), each attenuated the 8-OH-DPAT (3 mg kg-1, s.c.)-induced increase in mobility. 4. The dopamine D1 receptor antagonist, SCH 23390 (3-10 mg kg-1, p.o.), weakly reversed the 8-OH-DPAT response. Antagonists at 5-HTlc/5-HT2 receptors (ketanserin; 0.1-3.0 mg kg-1, p.o.),5-HT3 receptors (ondansetron; 0.03-10mg kg-1, p.o.), at-adrenoceptors (prazosin; 1-3mgkg-1, p.o.),alpha2 -adrenoceptors (idazoxan; 3-30mg kg-1, p.o.), alpha 1-adrenoceptors (metoprolol; 1-30mgkg-1, p.o.),beta 2-adrenoceptors (ICI 118,551; 1-30 mg kg-1, p.o.), dopamine D2 receptors (sulpiride; 10-300mg kg-',p.o.) and opiate receptors (naloxone; 3-100 mg kg-', p.o.) had no effect on the 8-OH-DPAT response.5. Selective destruction of 5-HT neurones with 5,7-dihydroxytryptamine or inhibition of 5-HT synthesis with p-chlorophenylalanine did not change the 8-OH-DPAT response in the Porsolt test. This response was also unaltered by pretreatment with the noradrenergic neurotoxin, DSP-4.6. Administration of 8-OH-DPAT (3 mg kg-1, s.c.) twice-daily for 10 days attenuated the hypothermia,but not the increased mobility, induced by 8-OH-DPAT (3 mg kg-1, s.c.). Similarly, repeated administration of amitriptyline (3-30 mg kg-1), desipramine (3-30 mg kg-1) or dothiepin (10-100 mg kg-1) also attenuated the former, but not the latter, response.7. We conclude that 8-OH-DPAT produces an antidepressant-like effect in the Porsolt test which is mediated via postsynaptic 5-HT1A receptors. PMID- 8467356 TI - Comparison of the regional haemodynamic effects of the AT1-receptor antagonists, losartan and EXP 3174, in water-deprived Brattleboro rats. AB - 1. Two separate groups (n = 8) of Brattleboro rats, chronically instrumented for the measurement of regional haemodynamics, underwent a 2-stage experimental protocol. Initially, animals had their drinking water removed and cardiovascular recordings were made every 30 min for the following 6 h. Then animals received either the AT1-receptor antagonist, losartan (3 mg kg-1, i.v., n = 8), or an initially equi-hypotensive dose of its active metabolite, EXP 3174 (1 mg kg-1, i.v., n = 8), and the resultant cardiovascular changes were monitored for a further 2 h. A third group of Brattleboro rats (n = 8) was water-deprived for 8 h to serve as a time control. 2. In all 3 groups of animals, mesenteric and hindquarters vasoconstriction (beginning approximately 30 and 120 min, respectively, after water was removed) occurred much earlier than changes in blood pressure, since increases in blood pressure were significant only after 5-6 h of water deprivation; renal perfusion was largely unchanged. The observation of a differential onset of haemodynamic changes (i.e. mesenteric > hindquarters >> renal) extends our previous findings, in which measurements were made only at the end of a 14 h period of water-deprivation. 3. When given after 6 h of water deprivation, losartan and EXP 3174 produced directionally similar, but temporally disparate, haemodynamic effects. EXP 3174 caused a depressor response associated with marked renal, mesenteric and hindquarters vasodilatations which were well maintained over 2 h. Losartan evoked similar changes to EXP 3174 in the first 5 min, but in contrast to EXP 3174, blood pressure showed some recovery and all 3 vascular conductance values returned to baseline (i.e. pre-drug)levels over the following 10-20 min. Thereafter, hypotension and renal, mesenteric and hindquarters vasodilatation again occurred, and these changes were maintained for the rest of the 2 h. However,compared with losartan, EXP 3174 caused significantly greater mesenteric and hindquarters vasodilatation,even at times when both compounds lowered blood pressure to the same extent.4. The biphasic cardiovascular response caused by losartan is consistent with the conversion of the parent compound to EXP 3174. Whether or not the enhanced vasodilator effect of EXP 3174 over losartan is related to pharmacodynamic differences (i.e., noncompetitive versus competitive antagonism,respectively), and/or to differences in the amount of EXP 3174 generated from losartan is not known at present. PMID- 8467357 TI - The regulation of aortic endothelial cells by purines and pyrimidines involves co existing P2y-purinoceptors and nucleotide receptors linked to phospholipase C. AB - 1. We have examined the phospholipase C responses in bovine aortic endothelial cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. The cells responded to purines in a manner consistent with the presence of P2y purinoceptors; both 2-methylthioadenosine 5'-triphosphate (2MeSATP) and adenosine 5'-0-(2-thiodiphosphate) (ADP beta S) were potent agonists (EC50 0.41 microM and 0.85 microM respectively) while beta, gamma methylene ATP at 300 microM was not. 3. The cells also responded to UTP. The maximal response to UTP was less than that for either 2MeSATP and ADP beta S while adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S) gave the largest maximal response. 4. The concentration-effect curve to UTP was additive in the presence of either 2MeSATP or ADP beta S. However, the concentration-effect curves to ATP gamma S reached the same maximum in the presence or absence of UTP. 5. Suramin, at concentrations between 10 microM and 100 microM was a competitive antagonist for the response to ADP beta S and 2MeSATP but not the response to UTP. 6. The results show that there are two separate, co-existing, receptor populations: P2y purinoceptors (responding to purines) and nucleotide receptors (responding to both purines and pyrimidines). We conclude that purines such as ATP/ADP may regulate aortic endothelial cells by interacting with two phospholipase C-linked receptors. PMID- 8467358 TI - Role of leukotrienes in airway hyperresponsiveness in guinea-pigs. AB - 1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen. PMID- 8467359 TI - Reversal by suramin of neuromuscular block produced by pancuronium in the anaesthetized rat. AB - 1. Rats were anaesthetized with sodium pentobarbitone and maximal twitches of a tibialis anterior muscle were evoked by stimulation of the motor nerve. 2. Suramin, injected intravenously in a series of cumulative bolus doses, each 15 mg kg-1, completely reversed a 90% depression of twitches maintained by a continuous intravenous infusion of pancuronium. The cumulated dose necessary to restore twitches to 50% of their control amplitude was 35 mg kg-1. Suramin did not modify a similar degree of block produced by suxamethonium, nor did it affect the amplitude of control maximal twitches, even in cumulative doses up to 150 mg kg 1. 3. The effects of bolus doses of suramin (85 mg kg-1), neostigmine (0.03 mg kg 1) and 4-aminopyridine (1.2 mg kg-1), calculated to restore pancuronium-blocked twitches to 95% of control amplitude, were compared. Suramin produced the most rapid reversal (1.1 +/- 0.5 min), but its duration of action was the shortest (9.4 +/- 1.6 min). Suramin was without effect on heart rate or blood pressure in the doses used. 4. The results showed that suramin reversed neuromuscular block produced by nondepolarizing blocking drug, pancuronium, but was without effect on a block produced by the depolarizing blocking drug, suxamethonium. Its short duration of action suggests that suramin would probably not be of value clinically as a reversal agent. However, it is possible that it might serve as a starter compound for the synthesis and development of a new class of reversal agents for use in anaesthetic practice. PMID- 8467360 TI - Effects of analogues of adenine nucleotides on increases in intracellular calcium mediated by P2T-purinoceptors on human blood platelets. AB - 1. By use of a number of analogues of adenine nucleotides, the structure-activity relationships of the human platelet receptor for adenosine 5'-diphosphate (ADP) mediating increases in intracellular calcium were investigated, and compared with the known structure-activity relationships for induction by ADP of platelet aggregation. 2. ADP, 2-methylthioadenosine 5'-diphosphate (2-methylthio-ADP), adenosine 5'-O-(1-thiodiphosphate) (ADP-alpha-S) and adenosine 5'-O-(2 thiodiphosphate) (ADP-beta-S) each induced increases in intracellular calcium in a manner similar to their reported ability to induce human platelet aggregation. The effects of these agonists were antagonized by ATP, with a pA2 value in each case consistent with the inhibition by ATP of ADP-induced aggregation. In the case of ADP, the inhibition by ATP of increases in intracellular calcium was shown to be competitive by Schild analysis. 3. Of the analogues tested as inhibitors of the effect of ADP on intracellular calcium, 2-chloroadenosine 5' triphosphate (2-chloro-ATP), adenosine 5'-O-(1-thiotriphosphate) (ATP-alpha-S), P1, P5-diadenosine pentaphosphate (Ap5A) and adenylyl 5'-(beta,gamma methylene)diphosphonate (AMPPCP) were apparently competitive antagonists, although only one concentration of each antagonist was used. There was a good correlation between the pA2 values found here for these antagonists including ATP, and their pA2 values reported for inhibition of ADP-induced aggregation. Adenosine 5'-(alpha, beta-methylene)triphosphate (AMPCPP) and uridine 5' triphosphate (UTP) (100 microM) were only very weak inhibitors of the effect of ADP on intracellular calcium, and this is consistent with their weak actions as inhibitors of aggregation. 2-Methylthioadenosine 5'-triphosphate (2-methylthio ATP) (50 microM) non-competitively inhibited the effect of ADP on intracellular calcium, in a very similar way to its inhibition of ADP-induced aggregation.4. The good correspondence found for these analogues between their effect on intracellular calcium and on aggregation confirms that there is a causal relationship between these actions of ADP, and that they are mediated by the same receptor on platelets. These findings cast further doubt on the use of the affinity reagent 5'-fluorosulphonylbenzoyladenosine (FSBA) as an antagonist and label for the ADP receptor, as this compound has been reported to inhibit aggregation but not ADP-induced increases in intracellular calcium. PMID- 8467361 TI - Characterization and ontogeny of P1-purinoceptors on rat vas deferens. AB - 1. The P1-purinoceptors which mediate the inhibition by adenosine of nerve mediated contraction of the rat vas deferens have been investigated by use of the agonists N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The ontogeny of the responses to adenosine and to the two co-transmitters which induce the contractions in this tissue, adenosine 5'-triphosphate (ATP) and noradrenaline (NA), have also been studied. 2. The order of potency for the adenosine agonists in inhibiting the nerve-mediated contractions was CPA = NECA > adenosine. Micromolar concentrations of DPCPX were required to antagonize the inhibition by adenosine and NECA of nerve-mediated responses, whereas the inhibitory effect of CPA was antagonized by nanomolar concentrations of the antagonist. 3. NECA and adenosine inhibited contractions induced by ATP (10 microM) or by NA (10 microM), NECA being at least ten fold more potent than adenosine, whereas CPA was inactive. Micromolar concentrations of DPCPX were required to antagonize the effect of adenosine on the contractions induced by ATP (10 microM). 4. Nerve-stimulated contractions could be observed in neonatal tissues from day 15 and increased with age, and could be inhibited by adenosine from this time, the potency of adenosine decreasing with age. Responses to ATP also appeared at day 15 and increased with age up to day 25, while responses to NA were present from day 10 (the earliest day tested) and decreased with age. 5. These results show that the rat vas deferens contains both prejunctional Al receptors and postjunctional A2-receptors, and that adenosine acts on the latter populations to inhibit nerve-mediated contractions.The high potency of adenosine in the neonate and the parallel development of responses to ATP and to nerve mediated contractions support suggestions that purinergic responses may be particularly important in neonatal tissues. PMID- 8467362 TI - The effect of NG-nitro-L-arginine methyl ester upon basal blood flow and endothelium-dependent vasodilatation in the dog hindlimb. AB - 1. The role played by the endothelium-derived relaxing factor (EDRF), nitric oxide (NO) in the regulation of blood flow to the skeletal muscle vasculature of the dog skinned hindlimb has been determined by examining the effects of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) upon (i) basal iliac artery blood flow, (ii) vasodilator responses to endothelium-dependent and independent agonists and (iii) reactive hyperaemic responses to arterial occlusion. 2. L-NAME (0.1-3 mg min-1) infused directly into the iliac artery dose dependently reduced basal iliac artery blood flow by a maximum of 48.6 +/- 6.9% (n = 4) and also increased mean systemic arterial blood pressure by 25.6 +/- 5.0 mmHg (n = 4) (at 3 mg min-1 L-NAME). 3. Over the same dose range, L-NAME also inhibited the peak vasodilator responses to intra-arterially administered, submaximal bolus doses of the endothelium-dependent agonists, bradykinin (3-300 ng) and acetylcholine (30-300 ng) by approximately 40%. In contrast, peak vasodilator responses to the endothelium-independent agonists, sodium azide (3-30 micrograms) and adenosine (0.3-1 mg), and peak reactive hyperaemic responses to arterial occlusion (60 s) were largely unaffected by L-NAME. 4. The dose-related effects of L-NAME on basal iliac artery blood flow, mean systemic arterial blood pressure and endothelium-dependent vasodilator responses were significantly attenuated by pretreatment with L-arginine (100 mg min-1) followed by co-infusion of L-arginine (100 mg min-1) with L-NAME. 5. In conclusion, these data suggest that NO plays some role in regulating basal blood flow and in mediating the vasodilator responses to the endothelium-dependent agonists bradykinin and acetylcholine in the skeletal muscle vasculature of the dog hindlimb. The substantial component (~60%) of the peak vasodilator responses to bradykinin and acetylcholine, unaffected by L-NAME, may be independent of NO, or be mediated by an alternative EDRF-dependent but L-NAME-insensitive mechanism. PMID- 8467363 TI - Differential effects of captopril on regional haemodynamic responses to angiotensin I and bradykinin in conscious rats. AB - 1. Conscious, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to allow regional haemodynamic (coeliac, mesenteric and hindquarters vascular beds) responses to i.v. bradykinin to be assessed in the absence and presence of captopril and of ganglion blockade (with mecamylamine). 2. Bradykinin (3 nmol kg-1, i.v. bolus) had no effect on mean arterial blood pressure, although it caused hyperaemic vasodilatation in the coeliac, mesenteric and hindquarters vascular beds. Following administration of captopril at a dose (28 nmol kg-1) which had no effect on responses to angiotensin I, the hypotensive and coeliac and mesenteric vasodilator responses to bradykinin were enhanced. However, there was a temporal dissociation between these events indicating that changes in cardiac output must have been contributing to the changes in mean arterial blood pressure. 3. Captopril at a higher dose (280 nmol kg-1) caused reversible inhibition of the pressor and coeliac and mesenteric vasoconstrictor effects of angiotensin I, but the inhibition of the mesenteric vascular responses was significantly less than that of the coeliac vascular responses. Under the same conditions, the mesenteric vasodilator effects of bradykinin were less enhanced than the coeliac vasodilator effects, consistent with greater inhibition of angiotensin-converting enzyme (i.e., kininase II) in the coeliac than in the mesenteric vascular bed. But, since the hypotensive action of bradykinin was markedly enhanced in these circumstances, the possibility existed that baroreflex responses influenced the haemodynamic effects of bradykinin. However, assessment of the haemodynamic changes following bradykinin administration(bolus or infusion) in the presence of ganglion blockade showed that only the hindquarters vasodilator response to bradykinin was enhanced, while the coeliac and mesenteric vasodilator responses were diminished. Thus, additional factors must have been influencing the latter responses.4. The results show that inhibition of angiotensin-converting enzyme (kininase II) can have differential effects on the regional haemodynamic responses to angiotensin I and bradykinin. The results provide a striking illustration of our previous assertion that the measurement of arterial blood pressure alone cannot provide sufficient information to allow interpretation either of the effects of vasoactive substances,or of the influence of drugs thereupon. PMID- 8467364 TI - Mediation via different receptors of the vasoconstrictor effects of endothelins and sarafotoxins in the systemic circulation and renal vasculature of the anaesthetized rat. AB - 1. Using endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin 6b (SX6b) and sarafotoxin 6c (SX6c) as agonists and BQ-123 as a selective ETA receptor antagonist, we have examined the endothelin receptor subtypes mediating the systemic pressor and renal vasoconstrictor effects of the ET/SX family of peptides. 2. In anaesthetized rats, bolus intravenous injections of ET-1, ET-3, SX6b or SX6c (0.1, 0.25 and 0.50 nmol kg-1) produced initial transient depressor responses followed by sustained and dose-dependent increases in mean arterial pressure (MAP) with the following rank order of potency: SX6b > ET-1 >> SX6c > ET 3. In contrast, in the renal vasculature these peptides caused equipotent dose dependent falls in renal blood flow (RBF) (ET-1 = ET-3 = SX6b = SX6c). 3. BQ-123 (1 mg kg-1, i.v. bolus) significantly reduced the systemic pressor effects of all the peptides but was largely ineffective against the renal vasoconstrictions. 4. These results indicate that although the systemic pressor effects of the ET/SX peptides are mediated via ETA receptors, the vasoconstriction in the kidney in vivo may be mediated predominantly via ETB-like receptors. This may be of therapeutic relevance, for an ETA-receptor-selective antagonist could offer only poor protection of the renal circulation from the deleterious effects of endogenously produced members of this peptide family. PMID- 8467365 TI - Amelioration by the Ca2+ antagonist, nimodipine of an existing neuropathy in the streptozotocin-induced, diabetic rat. AB - 1. Neuropathy is a frequently diagnosed complication in diabetic patients but an effective treatment does not exist. 2. The development of neuropathy in streptozotocin-induced diabetic rats was monitored by measuring the motor and sensory nerve conduction velocity in the sciatic nerve. 3. A significant decrease in sensory and motor nerve conduction velocity was apparent in young, 14-week-old diabetic rats as compared to non-diabetic, age-matched controls 4 weeks after the induction of diabetes with streptozotocin. 4. Intraperitoneal treatment with the Ca2+ channel blocker, nimodipine, from week 4 onwards, in a dosage of 10 mg kg-1 or 20 mg kg-1 intraperitoneally per 48 h, resulted in a significant increase in sensory and motor nerve conduction velocity whereas treatment with 5 mg kg-1 intraperitoneally per 48 h was not effective. 5. One-year-old, adult, diabetic rats treated with nimodipine 20 mg kg-1 (treatment started again 4 weeks after induction of diabetes mellitus) also showed an increase of both sensory and motor nerve conduction velocity as compared to diabetic rats treated with placebo. 6. It is concluded that nimodipine ameliorates existing experimental diabetic neuropathy in streptozotocin-induced diabetic rats in both young and adult animals. PMID- 8467366 TI - Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro. AB - 1. The centrally acting analgesic, tramadol, has low affinity for opioid receptors and therefore presumably other mechanisms of analgesic action. Neurotransmitter release and uptake experiments were used to characterize the effects of tramadol on the central noradrenergic and dopaminergic systems. 2. Tramadol inhibited the uptake of [3H]-noradrenaline into purified rat hypothalamic synaptosomes with an IC50 of 2.8 microM; the (-)-enantiomer was about ten times more potent than the (+)-enantiomer. Results with the principal metabolite O-desmethyltramadol were very similar. Inhibition of dopamine uptake into purified rabbit caudate nucleus synaptosomes was very weak with 62% inhibition of 100 microM. 3. Rat occipital cortex slices were preincubated with [3H]-noradrenaline and rabbit caudate nucleus slices with [3H]-dopamine, then superfused and stimulated electrically. Tramadol, 1 and 10 microM, enhanced the stimulation-evoked [3H]-noradrenaline overflow by 25 and 69%, respectively; the ( )-enantiomer was more potent than the racemate or the (+)-enantiomer. Tramadol, 10 microM, had no effect on dopamine release. 4. The effects of tramadol on the stimulation-evoked [3H]-noradrenaline release were abolished when uptake sites were already blocked by a high concentration of cocaine. 5. The metabolite O desmethyltramadol showed a slight facilitation of the stimulation-evoked noradrenaline release; the effect was more pronounced in the presence of a high concentration of naloxone. In the presence of cocaine, inhibition of the release was observed similar to the effect of morphine but less potent. 6. The results show that tramadol blocks noradrenaline uptake with selectivity as compared to dopamine uptake. The interaction with the noradrenaline transporter is stereoselective. The principal metabolite O-desmethyltramadol shows in addition to noradrenaline uptake inhibition, opioid inhibition of noradrenaline release. PMID- 8467367 TI - Effects of carbamazepine and baclofen on 4-aminopyridine-induced epileptic activity in rat hippocampal slices. AB - 1. Rat transverse hippocampal slices exposed to 100 microM 4-aminopyridine (4-AP) generate spontaneous epileptic discharges ranging in duration from short 50 ms 'interictal' bursts to long 0.5-2 s 'polyspike' activity. 2. Here we compared the effects of the commonly used anticonvulsant, carbamazepine (40 microM) and the antispastic drug, baclofen (2 microM) on the various types of burst. 3. Carbamazepine completely abolished long bursts whilst leaving shorter bursts intact. This is consistent with its known anticonvulsant properties. 4. Baclofen greatly reduced the frequency of short bursts but did not block the long bursts. Rather, they became significantly more prolonged, indicating that baclofen does not have an anticonvulsant action, and may be proconvulsant. 5. These results conflict with conclusions based on studies using models that exhibited only interictal bursts, and emphasize the need to use experimental epilepsies which generate several types of epileptic discharge to evaluate the effects of putative anticonvulsant drugs. 6. The present findings suggest that GABAB receptors play a role in the transition of benign interictal bursts to longer polyspike activity which could develop into seizures in the whole animal. PMID- 8467368 TI - Imagery ability and source monitoring: implications for eyewitness memory. AB - The present study investigated the effect of self-reported vividness of visual imagery on the ability to discriminate between memories derived from two external sources of information. Subjects were shown a film of a crime and were then given a written description of the event which included information not seen in the film. In a source monitoring task, high and low imagers were found to be equally proficient in recognizing items as previously presented, but high imagers were poorer at discriminating the source of items based on the written description. This finding is considered in terms of possible encoding and retrieval differences resulting from imagery vividness. The role of vivid visual imagery as a variable underpinning confusions in eyewitness testimony is discussed. PMID- 8467369 TI - Latent inhibition and recall/recognition of irrelevant stimuli as a function of pre-exposure duration in high and low psychotic-prone normal subjects. AB - Learning to ignore non-relevant stimuli (coloured geometric shapes) was evaluated in high and low psychotic-prone normal subjects in two experiments. In the first, subjects were tested in a latent inhibition paradigm in a 2 x 2 x 3 factorial design (high vs. low psychotic proneness, as measured by MMPI subscales; pre exposure of the stimuli such that they were non-relevant before the test but relevant in the test vs. absence of such pre-exposure; three levels of pre exposure duration: 3-, 6- and 15-min). Low psychotic-prone subjects showed the latent inhibition effect (poorer learning as a result of pre-exposure to the non relevant stimuli as compared to no pre-exposure) at 6- and 15-min durations, but not at 3-min. High psychotic-prone subjects failed to show latent inhibition at 3 and 6-min durations, but did show the effect at 15-min. The second experiment employed a 2 x 3 design (high vs. low psychotic proneness; three levels of pre exposure duration of the same stimuli used in Expt 1). High psychotic-prone normal subjects recalled and recognized more previously non-relevant stimuli than low psychotic-prone subjects, particularly after 6-min pre-exposure to those stimuli. The data of the two experiments suggest that the attenuation of latent inhibition in high psychotic-prone subjects as compared to low psychotic-prone subjects is a result of the increased attention to non-relevant information. PMID- 8467370 TI - On what intelligence is. AB - Despite much controversy over the exact definition of intelligence, most researchers agree that it is a concept labelled by a word, or even several related concepts labelled by a word. The present study applies recent theorizing about the nature of concepts in general to clarify the notion (or notions) of intelligence. This theorizing defines a concept as a person's unique and individual information about a category and a category as a set of things in the world. An example of a concept/category pair is 'dog', with the category being the set of all dogs and an individual's concept of dog being his or her personal knowledge of dogs. This knowledge can be used to place things in or out of the category. Different individuals may have somewhat different knowledge about the same category and a single word may label several different concept/category pairs. A concept of intelligence thus consists of information about a general category labelled by the word 'intelligence'. This study analyses three major concept/category pairs of 'intelligence': (1) Spearman's g; (2) intelligence as a property of behaviour; and (3) intelligence as a set of abilities. Each concept contains different information, refers to a different category, and should be used in different ways. Several recurrent issues, such as whether the word 'intelligence' refers to a thing and what things are intelligent (e.g. animals, computers), can be resolved by considering each issue in relation to these concept/category pairs. For instance, the word 'intelligence' refers to a thing only if one uses the g concept. Similarly, only humans are intelligent according to the g concept but animals and computers may be considered intelligent if the other concepts are applied. Recent theorizing on the nature of concepts can be used to clarify other important psychological notions. PMID- 8467371 TI - Recognition and recall of visual area. AB - When visual areas are recalled the ratio of two areas is compressed relative to both the actual and perceived values (e.g. Kemp, 1988). Experiment 1 replicated this effect with a simple two-region figure, and Expt 2 showed a significant increase in area compression to occur between 2 min and 1 week when subjects were asked to recognize the two-region figure from a set of nine figures with different area ratios. Area compression was also found in Expt 3 where a different figure was used. Experiment 4 found that varying the texture of the smaller region of a two-region figure had no significant effect on area compression, and in Expt 5 subjects choose a figure in which the area was expanded but the texture was unchanged over one in which the texture was expanded with the area. Experiment 6 showed that compression of remembered areas seen in a photograph did not depend on recalled distance. In conclusion, area compression appears to arise from a gradual transformation of remembered area that does not resemble a zooming process. PMID- 8467372 TI - Potency in groups: articulating a construct. AB - This paper examines potency, defined as the collective belief in a group that it can be effective, and its role in determining group effectiveness. The paper illustrates the construct and reviews its origins. The distinctiveness of potency from efficacy and from other collective and motivational constructs is described. The measurement of potency is also examined. The paper concludes with a presentation of a conceptual framework for understanding the determinants of potency and with a discussion of future theory, research and practice. PMID- 8467373 TI - Hemisphericity and top-down processing of language. AB - This study investigated the impact of contextual prompts (priming words and sentences) on the classical finding of superior performance with right visual field stimulation in a lexical decision task. Subjects were presented with prompts of varying lengths (one, three, or six words). The prompts were followed by a target stimulus (word/nonword) to the right or the left visual field. Subjects were required to respond whether the target was a word or a nonword. The major purpose of the study was to determine the extent of right visual field (RVF) superiority, reflecting left hemisphere superiority, in language processing when target stimuli are preceded by semantically meaningful prompts. The results showed that increasing the number of priming words congruent with the target (creating a meaningful context) increased the advantage of the RVF over the left visual field presentation in lexical decision. Thus, even with an available strategy provided by congruent priming stimuli, RVF superiority in lexical decision is retained and even increased. PMID- 8467374 TI - "Auditory neglect after right frontal lobe and right pulvinar thalamic lesions": comments on Hugdahl, Wester, and Asbjornsen (1991) and some preliminary findings. AB - We take issue with the claim recently made in this journal that extinction of left ear input during dichotic, but not monaural, stimulus presentation demonstrates "auditory attentional neglect" (Hugdahl, Wester, & Asbjornsen, 1991). We also report on a patient suffering from unilateral visual neglect, who shows extinction under dichotic, but not monaural, conditions of stimulus presentation but this is not confined to one ear. Although this patient denies hearing both of two dichotically presented words, he recognizes the extinguished stimulus when given a forced-choice recognition task. PMID- 8467376 TI - Pragmatic language skills after closed head injury: ability to meet the informational needs of the listener. AB - Two closed-head-injured subjects and 12 non-brain-damaged controls explained a novel procedure to a blindfolded third person. Their productions were transcribed and scored by nine judges on ratings scales based on Grice's maxims of quantity and manner. The two closed-head injury (CHI) productions were significantly inferior to the controls, both being rated as disorganized, confusing, and ineffective. While one subject's production was considered overly repetitive, the other had too little detail. In order to specify, more exactly, the nature of the deficits, a cohesion analysis and an analysis of informational content were performed. The cohesion analysis suggested that the CHI productions were generally similar to the controls. The informational analysis was more revealing. Judgements of detail and repetitiveness were reflected in the number of new and repeated propositions. Errors in sequencing and inclusion of irrelevant propositions contributed to the disorganized and confusing nature of the texts. The results were interpreted within the framework of frontal lobe deficits in monitoring and regulation of performance. PMID- 8467375 TI - Dissociation of cortical and single unit activity in spoken and signed languages. AB - Based on stroke and other lesion data, the cortical organization of sign language has been shown to be in the verbal language-dominant hemisphere. However, finer detail of the cortical organization of sign language is not readily available. Intraoperative cortical mapping of spoken and American Sign Language (ASL) was performed in a hearing patient proficient in ASL undergoing an awake operation for intractable epilepsy. We found the dissociation of essential cortical language sites for spoken and signed languages, the relationship of these sites to the interpretation of ASL, and the importance of the anterior temporal lobe in the language-dominant hemisphere for proper ASL handshapes. Single unit recordings in the anterior temporal lobe, at a site later identified to be important in handshape formation, showed sustained activity during naming with superimposed increases in activity during overt speech. PMID- 8467377 TI - A personal case history of transient anomia. AB - The article presents a first-person account of a transient anomia or word-finding deficit; the assumption is that such an account, reported by someone with a professional background in memory, cognition, and language processes, may shed additional light on the nature of an anomic episode and on the subjective experience of memory and language disruption due to brain-related abnormalities. During the 45-min episode, I was unable to retrieve and use specific content words and terms ("data," "experiment," "printout") in overt speech. I was completely conscious of these target concepts, although not of their names, and was aware of my inability to find the words. Neither word finding for "everyday" words nor ongoing thought processes were particularly disrupted. The nature and quality of my thoughts during the episode indicate no loss of awareness of circumstances or "presence of mind," but no genuine awareness of the seriousness of the episode. I briefly consider the implications of my experience and the similarities to another published case history. PMID- 8467378 TI - "Virtual N400" and slow wave topography to auditory sentence incongruence. AB - In a simple auditory sentence paradigm, two ERP components were found to be sensitive to violations of sentence congruence: a "virtual N400" and the Slow Wave (SW). Unlike previous studies, the N400 was found to occur very early (peak latency of 250 msec) and have a short duration (196-287 msec), while maintaining the previously described slightly asymmetric right central-parietal negative topography. Because of the early latency, this component was referred to as a "virtual N400." The SW (418-530 msec) was also enhanced and topographically shifted to incongruent sentence terminal words. Its topography consisted of a symmetric frontal minimum and posterior maximum. Although the difference map was also symmetric, a t value map of the congruence effect was maximal over the left posterior temporal area. The very early latency of the "virtual N400" and its decreased duration were produced by a paradigm that allowed for very early recognition of a semantic violation, even before the spoken word was complete. It is postulated that the "virtual N400" indexes word recognition. Semantic processing in indexed by the "virtual N400" as well, but the left posterior temporal asymmetry in the t maps of the Slow Wave may be of even greater import. PMID- 8467379 TI - Semantic processing in the right hemisphere may contribute to drawing inferences from discourse. AB - After listening to multiple-episode stories that promoted coherence inferences, right hemisphere-damaged patients answered Inference questions about the stories less accurately than Explicit questions, whereas normal elderly subjects answered both question types equally well. In addition, while subjects listened to the stories they made lexical decisions to tests words that were related to the promoted inferences or were unrelated to the stories. Right hemisphere-damaged patients responded more slowly to inference-related words than to unrelated words, whereas normal elderly subjects responded more quickly to interference related words than to unrelated words. Furthermore, the episode boundaries did not affect either group's accuracy on Inference questions, and the boundaries equally affected both groups' lexical decision latencies, suggesting that the patients' inferencing deficit was not due to an impairment in organizing the mental substructures used to represent discourse. These results suggest that the right hemisphere-damaged patients lacked activation of semantic information necessary for drawing coherence inferences. PMID- 8467381 TI - Long-term changes in the neuromuscular synapses of a crayfish motoneuron produced by calcium influx. AB - Previous in vivo studies of crustacean neuromuscular synapses have shown that a chronic increase in the impulse activity of a previously 'inactive' motoneuron produces a reduction in initial transmitter release and greater resistance to synaptic fatigue. To explore the mechanisms of this synaptic change, we have developed an in vitro procedure for examining this activity-dependent reduction in initial transmitter release. We report that depolarization selectively applied to the proximal region of the neuron (cell body or axon) of a phasic motoneuron produces a reduction in initial transmitter release from the motor terminals. This synaptic change is observed 4-5 h after the beginning of depolarization. Proximal depolarization decreases initial transmitter release without reducing the capacity of the terminals to release transmitter during repetitive stimulation. Application of a calcium channel blocker during conditioning prevents the reduction in initial transmitter release. These results demonstrate that prolonged calcium influx produce a long-term reduction in initial transmitter release, and that calcium influx in distant regions of the motoneuron can influence transmitter release from motor terminals. The relationship of these findings to previously reported activity-dependent synaptic changes is discussed. PMID- 8467380 TI - The developmental pattern of rabbit brain insulin and insulin-like growth factor receptor expression. AB - To examine the effect of development on rabbit brain insulin and insulin-like growth factor (IGF) receptor expression, we characterized and quantitated receptor mRNAs by Northern blot analysis and affinity-labeled ligand bound receptors by SDS-PAGE and autoradiography. At various stages of development ranging from 23 to 30 day gestational (term approximately 31 days), 1 to 10 day postnatal ages and the adult, no change in the whole brain insulin receptor mRNA (7.0, 6.0 and 5.5 kb) and affinity-labeled receptor protein (approximately 125 kDa) levels was observed. The IGF-I receptor mRNA (11.5, 6.5 and 4.5 kb) and affinity-labeled receptor (approximately 125 kDa) protein levels declined during the neonatal stages of development. In the case of the IGF-II receptor, while the mRNA levels (9.0 and 4.5 kb) remained constant, the corresponding affinity labeled receptor protein (approximately 230 kDa) declined with maturation. We conclude that a differential regulation of brain insulin, IGF-I and IGF-II receptor expression occurs during development. PMID- 8467382 TI - Destruction of the locus coeruleus decreases physical signs of opiate withdrawal. AB - The purpose of the present study was to investigate the role of the locus coeruleus in the development of opiate dependence. Two groups of rats each were subjected to either a electrolytic lesion of the locus coeruleus or a sham lesion. All animals were implanted with an intracerebroventricular (i.c.v.) cannula, and made physically dependent by subcutaneous insertion of two 75-mg morphine (base) pellets. Abstinence was precipitated by i.c.v. administration of methylnaloxonium (31-1,000 ng) 72 h after pellet implantation. Methylnaloxonium administered intracerebroventricularly induced a withdrawal syndrome characterized by the appearance of teeth chattering, mastication, rearing, wet dog shakes, jumping, piloerection, hyperactivity, ptosis and eye twitch. Withdrawal observed in the electrolytic lesion groups was less severe than in sham group. The presence of mastication, rearing, piloerection, hyperactivity, ptosis and eye twitch was significantly lower. These results support the hypothesis that the locus coeruleus has an important role in the expression of the physical signs of opiate dependence. PMID- 8467383 TI - Distribution of thyrotropin-releasing hormone binding sites: autoradiographic study in infant and adult human hippocampal formation. AB - The rostrocaudal distribution of thyrotropin-releasing hormone (TRH) binding sites was studied in the human hippocampus. Cryostat sections of the right and left hippocampi from 6 infants (2 h to 5 months of age) and 11 adults (24 to 92 years) were subjected to in vitro quantitative autoradiography using [3H]MeTRH as a ligand. A single class of high affinity [3H]MeTRH binding sites with an apparent dissociation constant in the nanomolar range has been shown both in the infant and the adult. The maximal number of these sites was higher in the infant. No significant difference was observed between the general patterns of the right and the left hippocampi when taking postmortem delay and age as parameters. The highest concentrations of [3H]MeTRH binding sites were localized in the uncinate gyrus, the uncal subiculum and in the whole length of the molecular layer of the dentate gyrus. The lowest densities were present in the ventral subiculum. The major difference observed between the infant and the adult appeared in the molecular layer of the dentate gyrus where the densities were two-fold higher in infants (189 +/- 6 versus 88 +/- 2 fmol/mg of tissue). The only marked difference in the distribution was localized in the caudal part of the body where no specific labeling was found in the presubiculum of the infant. PMID- 8467384 TI - Membrane-bound choline-O-acetyltransferase in rat hippocampal tissue is anchored by glycosyl-phosphatidylinositol. AB - In an earlier study, we presented evidence to suggest that some of the particulate choline-O-acetyltransferase (ChAT) in rat hippocampal tissue might be linked to membranes by a glycosyl-phosphatidylinositol (GPI) anchor. In the present report, we attempted to determine if any of this GPI-anchored ChAT might be intracellular. Internalization of phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis into rat hippocampal synaptosomes by the DMSO (dimethyl sulfoxide) freeze/thawing procedure caused an increase in cytosolic and a decrease in membrane-bound ChAT. Incubation of a plasma membrane enriched subcellular fraction at 16 degrees C relative to 4 degrees C led to a conversion of the membrane-bound, amphiphilic ChAT into hydrophilic ChAT. This conversion was blocked by zinc, an inhibitor of GPI-PLC. The cytosolic fraction of ChAT immunoreacted on western blots with an antibody directed against the cross-reacting determinant (CRD) of the GPI anchor. We suggest that some of the membrane-bound ChAT in rat hippocampal tissue is GPI-anchored intracellularly; also, that an endogenous GPI-PLC-like enzyme acts to release it into the cytosol. PMID- 8467385 TI - Transient increase in endogenous basic fibroblast growth factor in neurons of ischemic rat brains. AB - An antiserum against basic fibroblast growth factor (bFGF) was shown to recognize an 18-kDa protein (possibly bFGF) in crude neocortical extracts by immunoblot and used to investigate the changes of bFGF immunoreactivity in neurons and astrocytes of the cerebral cortex of rats 1-21 days after unilateral occlusion of the middle cerebral artery (MCA). The mildly ischemic neocortex exhibited no signs of cell loss or degeneration in Nissl-stained sections 1-14 days after MCA occlusion, but it contained pyramidal cell bodies and processes with more intense bFGF immunoreactivity than did the control neocortex. bFGF immunoreactivity in the ischemic hemisphere gradually declined in intensity and by 21 days after MCA occlusion, it had reached the control level. On the other hand, there were many bFGF immunoreactive astrocytes in the primary olfactory cortex on the side of infarction. These findings suggest that MCA occlusion causes an increase in bFGF content not only in astrocytes but also in neurons, depending on the severity of the ischemic insult in individual cortical regions. The transient augmentation of bFGF expression or accumulation in mildly ischemic pyramidal neurons but not in astrocytes is in line with previous studies suggesting the neurotrophism of exogenously applied bFGF. PMID- 8467386 TI - Glucocorticoid and mineralocorticoid receptors in rat neocortical and hippocampal brain cells in culture: characterization and regulatory studies. AB - Glucocorticoid and mineralocorticoid binding sites were characterized in cell cultures derived from neocortical and hippocampal brain tissue from fetal (E18) rats. Specific and saturable binding was detected in living cells with a sensitive whole cell binding method using [3H]dexamethasone ([3H]DEX) and [3H]aldosterone ([3H]ALDO) (in the presence of RU 28362, a selective glucocorticoid receptor (GR) agonist) as ligands for the measurement of glucocorticoid and mineralocorticoid receptors (MRs), respectively. Specific corticosteroid binding was demonstrated as early as day 4 in culture in neocortical cells, with a time-dependent increase in binding sites during further culturing time. At 7-9 days in vitro, Scatchard analysis of [3H]DEX binding revealed a maximum binding capacity (Bmax) of 83.4 +/- 5.0 fmol/mg protein and a binding affinity (Kd) of 3.6 +/- 0.4 nM in neocortical brain cells. Competition binding studies with [3H]DEX demonstrated a glucocorticoid specificity of receptor sites (relative binding affinity: RU 28362 = DEX > PROG > ALDO). Similar binding characteristics were demonstrated for GRs in cultures derived from fetal hippocampal tissue (Bmax 49.1 +/- 5.8 fmol/mg protein, Kd 3.5 +/- 0.2 nM). Analysis of MRs with [3H]ALDO (+RU 28362) revealed specific and saturable binding in hippocampal cultures, with a Bmax of 8.0 +/- 0.5 fmol/mg protein and a Kd of 0.2 +/- 0.1 nM. Competition studies with [3H]ALDO showed a mineralocorticoid-like pattern of receptor binding (relative binding affinity: CORT = ALDO > PROG > DEX). In addition, small numbers of MRs were detectable in cortex-derived cultures (Bmax: 3.7 +/- 0.8 fmol/mg protein, Kd: 0.3 +/- 0.2 nM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467387 TI - Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. AB - Previous studies have shown that spontaneous exploration of the Elevated Plus Maze provides a sensitive measure of 'anxiety' induced by pharmacological or behavioral stressors. In particular, the percent time spent exploring the open arms of the plus maze is decreased during ethanol withdrawal, and this effect is antagonized by intracerebroventricular administration of 25 micrograms of alpha helical CRF, a corticotropin-releasing factor antagonist (H.A. Baldwin et al., Psychopharmacology, 103 (1991) 227-232). The present study was designed to examine the effect of alpha-helical CRF infusion within the central nucleus of the amygdala during ethanol withdrawal. Rats were made dependent on ethanol by maintenance on an ethanol-containing liquid diet for 16 days, withdrawn from ethanol and tested on the elevated plus maze at 8 h post-ethanol access. In comparison with pair-fed control rats, ethanol withdrawn subjects spent significantly less percent time exploring the open arms of the plus maze. This decrease in open arm exploration was antagonized by administration of alpha helical CRF (250 ng) bilaterally into the central nucleus of the amygdala, but not by intracerebroventricular administration of 250 ng of alpha-helical CRF. The ability of intra-amygdala alpha-helical CRF to antagonize decreased open arm exploration is unlikely to be due to changes in motor activity, since general activity on the maze was reduced in all EtOH withdrawal groups. These results suggest that the central nucleus of the amygdala may be an effective site for endogenous CRF systems to mediate anxious behavior associated with ethanol withdrawal. PMID- 8467388 TI - Nerve growth factor and a fibroblast growth factor-like neurotrophic activity in cerebrospinal fluid of brain injured human patients. AB - We report here the presence of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) of some brain-injured human patients soon after injury. The NGF was quantified against a recombinant human NGF standard in a two-site enzyme-linked immunoabsorbent assay using antibodies against murine B NGF. None of the samples collected more than 2 days after injury contained detectable levels of NGF. When the CSF was assayed for the ability to promote neurite outgrowth from PC12 cells, neurite outgrowth was reduced, but not completely blocked, by antibodies to B NGF, suggesting that there were other biologically active factors present. Fibroblast growth factor (FGF) also promotes neurite outgrowth in PC12 cells. In an initial screening for the presence of FGF, we employed PC12 cells and NR119 cells, PC12 variants in which recombinant human B NGF, but not recombinant human basic FGF, promotes neurite outgrowth. CSF from brain injury patients promoted greater neurite outgrowth from PC12 cells than from NR119 cells, suggesting that some of the biological activity associated with the injury CSF may be due a FGF. This possibility is further supported by the observation that the biological activity of the injury CSF significantly reduced by batch absorption with heparin Sepharose, suggesting the presence of a heparin binding neurotrophic factor. Neurotrophic factors appear in CSF as a consequence of diverse types of brain injury, including head trauma, intracerebral hemorrhage and subarachnoid hemorrhage. The appearance of these factors may reflect important common elements in the complex series of cellular changes occurring in response to acute brain injury. PMID- 8467389 TI - Reversible tetracaine block of rat periaqueductal gray (PAG) decreases baseline tail-flick latency and prevents analgesic effects of met-enkephalin injections in nucleus paragigantocellularis (PGC). AB - One micrograms of tetracaine in the rat periaqueductal gray (PAG) produced a decline in baseline tail-flick latencies (hyperalgesia) from about 5 to 3.5 s over the course of 9 min, after which the latencies increased to about 4.5 s. One micrograms of Met-enkephalin in PGC caused an expected increase in latencies (analgesia) from about 4.25 to 6.2 s in 9 min, with recovery to 4.7 s after 15 min post-injection. Giving the preceding 2 nanoinjections simultaneously led to an essentially total block of the PGC analgesia. A control injection in PAG simultaneous with a Met-enkephalin injection in PGC did not block the latter's analgesic effect. Single control (artificial cerebrospinal fluid) injections in PAG or PGC were without effect. The hyperalgesic effect of PAG tetracaine supports the involvement of PAG in normally occurring, tonic descending pain inhibition. The block of PGC met-enkephalin analgesia by distant injection of tetracaine in PAG supports the necessity of PAG integrity for PGC analgesic function. PMID- 8467390 TI - Differential distribution of the alternative forms of the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase, SERCA2b and SERCA2a, in the avian brain. AB - Cellular distribution of the two forms of SERCA2 was examined in adult chicken brain. Four regions of the brain were analyzed with three immunological reagents: a monoclonal antibody that recognizes both forms of SERCA2, and two antisera which are specific for the two alternative forms, SERCA2b or SERCA2a. Cerebellar Purkinje cells express predominantly SERCA2b but also low levels of SERCA2a, as has been reported for mammals. The nucleus isthmo-opticus, nucleus magnocellularis cochlearis, and nucleus laminaris all express high levels of SERCA2 but with different ratios of SERCA2b and SERCA2a. These immunohistochemical results were supported by in situ hybridization analysis. Therefore, it appears that regions within the brain have specific requirements for the two forms of SERCA2. This suggests functional significance for the alternative forms SERCA2b and SERCA2a, and possible functions are discussed. PMID- 8467391 TI - Ratification of broiler carcase condemnations in poultry meat inspection. AB - 1. In the years 1985 to 1989 decisions (approvals and condemnations) made by poultry meat inspectors were examined by the individual reinspection of 26,815 broiler carcases. 2. The extent of agreement between inspection and revision ranged between 83.2 and 86.2%. 3. Agreement between inspectors and revisors was higher for the category of approved birds than for the condemned category. 4. Differences in the criteria used to assess the birds were observed. 5. The conclusion was drawn that findings in meat inspection require further discussion to reach an agreed standard. PMID- 8467392 TI - Artificial light sources and their influence on physical activity and energy expenditure of laying hens. AB - 1. The influence of fluorescent and incandescent artificial lighting in a 16L:8D day/night schedule on number and intensity of movements, and on total, resting and activity-related energy expenditure was investigated. 2. Fluorescent light showed the same positive correlation between light intensity and physical activity at all activity levels as was found previously for incandescent light. 3. Light-dependent physical activity under fluorescent light was higher than under incandescent light at illuminances of 5 lux and above, indicating the fowl's ability to perceive qualitative light differences. 4. Total and activity related energy expenditure were positively associated with illuminance; resting energy expenditure was not influenced. 5. Total, resting and activity-related energy expenditure were not statistically significantly different between light sources. 6. The results are discussed in relationship to Teichmuller's concept of adequate lighting and the characteristics of the fowl's visual system. PMID- 8467393 TI - Improvement of dietary protein utilisation in chicks by medium chain triglyceride. AB - 1. To improve the influence of variation of ME intake, an experiment was carried out using equalized feeding to investigate the comparative effects on protein and energy utilisation in chicks of diets containing medium chain triglyceride (MCT) and long chain triglyceride (LCT). Experimental diets were given at 3 different food intakes, namely, 100, 120 or 147 g/bird/10 d. The diets contained MCT or LCT on an isoenergetic basis. Maize oil and caprylic acid triglyceride respectively, were used as LCT and MCT sources. 2. Body weight gain and food efficiency of chicks significantly increased with the supplement of dietary MCT compared with dietary LCT at all food intakes. Protein retention and the efficiency of protein utilisation (protein retained/protein intake) at all food intakes also significantly increased with dietary MCT, while body fat and fat retention were significantly reduced. Chicks fed the LCT-supplemented diet, on the other hand, had a lower protein retention, but significantly higher fat retention. The value for energy retention and the efficiency of energy utilisation (energy retained/ME intake) were not significantly different between MCT- and LCT-supplemented diets. 3. It was concluded that supplementing MCT to the chick diet would improve body weight gain and protein utilisation while regulating fat deposition compared to the LCT supplemented diet, under equalized feeding conditions. PMID- 8467394 TI - Effects of feeding deoxynivalenol-contaminated oats on reproduction performance in White Leghorn hens. AB - 1. The effect of feeding trichothecene-contaminated diets with graded concentrations of deoxynivalenol ranging from 120 to 4900 micrograms/kg to groups of laying hens was investigated. 2. Food intake, weight gain and egg production were not affected by mycotoxin administration. No significant differences were found between groups. 3. The overall results from the hatching tests did not reveal any significant differences in fertility, hatchability or perinatal mortality, which could be explained by the mycotoxin content in the diets. 4. Body weight at hatching and viability of the chicks were not affected by the mycotoxin concentrations in the diets. 5. The incidence of chick developmental anomalies was increased in the mycotoxin-administered groups compared to controls. Minor malformations were the dominating anomalies and included unwithdrawn yolk sac and delayed ossification. The most frequent major malformations were cloacal atresia and cardiac anomalies. PMID- 8467395 TI - Effect of pyridoxine on the distribution of chloramphenicol and its residues in the chicken. AB - 1. Chickens were given either a single dose of chloramphenicol (50 mg/kg body weight per os) or a dose of chloramphenicol together with pyridoxine (25 mg/kg per os) given 1 h before or 4 h afterwards. 2. Concentrations of chloramphenicol were determined in samples of serum and the rates of distribution and elimination extrapolated. Concentrations of chloramphenicol in muscle, liver and kidney were also determined. 3. Serum concentrations of chloramphenicol were lower in chickens given both pyridoxine and chloramphenicol compared with those given only chloramphenicol. 4. Differences were most pronounced during the post-absorptive phase. The rates of disappearance of chloramphenicol residues from tissues were enhanced by pyridoxine. 5. The biological half life of chloramphenicol and area under the concentration-time curve were both reduced by the concurrent administration of pyridoxine. 6. Availability of pyridoxine may be a rate limiting factor in the biotransformation of xenobiotics, though its indiscriminate use could cause failure of antibiotic therapy. PMID- 8467396 TI - Effects of a beta-adrenergic agonist (clenbuterol) on performance, carcase composition, hepatic microsomal mixed function oxidase and antibody production in female broilers treated with or without corticosterone. AB - 1. Beta-adrenergic agonist (Clenbuterol, 0.33 mg/kg) and corticosterone (10 mg/kg) were incorporated into a diet based on maize and soybean meal. Their effects on performance, carcase composition, hepatic microsomal mixed function oxidase and antibody production were investigated in female broilers. 2. Dietary corticosterone reduced the titre to sheep red blood cells, while it was unchanged by clenbuterol. 3. Clenbuterol exerted a promoting effect on gain-to-food ratio, carcase protein and hepatic microsomal cytochrome P-450 content. 4. Addition of clenbuterol to the corticosterone-containing diet prevented the increase in abdominal fat weight and uric acid excretion induced by corticosterone, but did not affect total fat mass. 5. The results showed that clenbuterol reduced abdominal rather than carcase fat and prevented protein degradation in the body when chicks were treated with corticosterone. Clenbuterol also influenced the content of cytochrome P-450, but not the humoral immunity. PMID- 8467397 TI - Effect of cold stress on performance and immune responses of Bedouin and White Leghorn hens. AB - 1. Bedouin chickens are kept in deserts mainly for eggs and are well adapted to arid conditions. However, deserts are also characterised by relatively cold winter nights. As a consequence of cold stress there is an involution of lymphoid organs and a depression of immunological function. We compared the performance and immunological responses of Bedouin and White Leghorn hens kept in outdoor pens in the Negev Desert during the winter. 2. Initial mean body mass was similar for the two breeds: 1525 g for Bedouin hens and 1542 g for White Leghorn hens. White Leghorns lost 7.74 g/d, compared with 0.60 g/d for Bedouin hens and produced 0.36 eggs/d, compared with 0.54 eggs/day for Bedouin hens. 3. The heterophil/lymphocyte ratio for Bedouin hens was 0.28, which was lower than the 0.44 for White Leghorn hens. Phagocytic index was higher in Bedouin hens than in White Leghorns. Furthermore, wattle index measured 24, 48 and 72 h after PHA injections and anti-SRBC antibody titres determined 10 d after challenge were also higher in Bedouin hens than in White Leghorns. 4. We concluded that the Bedouin hens were less stressed by the cold than were the White Leghorn hens. PMID- 8467398 TI - Comparison of the rates of proliferation of adipocyte precursor cells derived from two lines of chicken which differ in their rates of adipose tissue development. AB - 1. Putative adipocyte precursor cells were isolated from the white adipose tissue of young broiler and layer chickens and cultured in vitro. 2. The cells from both sources were shown to have the characteristics of adipocyte precursor cells. On reaching confluence, lipoprotein lipase activity was induced and the cells from both strains accumulated large amounts of lipid in the presence of chicken serum. 3. Measurement of cell number over time in culture and calculation of cell doubling times showed that cells from broilers proliferated at a faster rate than those derived from layer-strain chickens. This was the case whether primary or secondary cell cultures were used. Primary cultures of broiler cells had a doubling time of 22 h versus 39 h for layer cells. 4. The contribution of such a difference in proliferative rate to the differential rate of adipose tissue growth between broiler and layer strains observed in vivo is discussed. PMID- 8467399 TI - Pharmacokinetic profile and tissue distribution of monensin in broiler chickens. AB - 1. The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. 2. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 h, volume of distribution of 4.11 l/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 h after intracrop dosage with an absorption half-life of 0.27 h and an elimination half life of 2.11 h. The systemic bioavailability was 65.1% after intracrop administration. Serum protein-binding tendency of monensin calculated in vitro was 22.8%. 3. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin premix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 h after oral administration. The highest concentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 h after the last oral dose. No monensin residues could be detected in tissues after 48 h, except in liver which cleared completely by 72 h. PMID- 8467400 TI - Further studies of linkage and mappings of the loci of genes in group 3 on chromosome 1 of the domestic fowl. AB - 1. Evidence is presented to confirm the placing of the extended black E-locus in linkage Group 3 on chromosome 1, E being linked with peacomb P by 43 map units. P has been shown to be linked with dark-brown columbian Db and sleepy-eye se by 32 and 45 map units, respectively, se being independent of E. 2. Evidence is also presented to demonstrate independence of E and Db; hence, Db and se have their loci on the same side of P, the gene order being E-P-Db-se, thus contradicting published mappings which place P between Db and se. 3. An investigation into the deductive relationships on which published mappings are based led to the conclusion that insufficient evidence existed for the inclusion of the sub-group comprising blood group Ea-P, naked neck Na, silky feathering h and flightless Fl as part of Group 3. 4. Furthermore, it appears only 4 genes in Group 3 have actually had their loci mapped; blue egg O, P, the eumelanin extension charcoal cha and the feather growth restrictor tardy t. 5. No evidence appears to have been presented to establish on which arm of chromosome 1 any of the other genes in Group 3 have their loci. A revised map of chromosome 1 and a schematic arrangement to demonstrate the relative linkage distances of the loci of the unmapped genes in Group 3 are presented and explained. PMID- 8467402 TI - Photoperiod and seasonal influences on the growth of turkey hens. AB - 1. The influence of photoperiod and time of year on the growth of hen turkeys was investigated. 2. Photoperiod treatments consisted of computer simulations of day lengths which occur naturally in the spring and autumn of the year. Both photoperiod treatments were given to hens in the autumn and spring. 3. Data were collected for growth evaluations at 2- to 4-week intervals to 16 weeks of age. No significant season X photoperiod interactions occurred. 4. The spring trial resulted in greater body weights and better food conversions (food/gain) than the autumn trial. 5. Simulated autumn daylengths resulted in greater body weights and improved food efficiency at 16 weeks of age compared with simulated spring daylengths. 6. The pattern of growth (period changes) was influenced by season, but not photoperiod. 7. Season and photoperiod both have important and independent influences on the growth of the turkey hen. PMID- 8467401 TI - Feeding behaviour in chickens given diets containing medium chain triglyceride. AB - 1. The effect of dietary medium chain triglyceride (MCT) on short-term food intake was compared with the effect of long chain triglyceride (LCT) in chickens. Maize oil was used as the LCT while glyceryl tricaprylate (C 8) and glyceryl tricaprate (C 10) were used as MCT. Cumulative food intake was determined during the 6 h after the start of feeding. 2. Chicks were given diets containing 200 g C 8/kg diet, 200 g C 10/kg diet or 200 g LCT/kg diet in experiment 1. As early as 30 min after feeding, cumulative food intake in both MCT-supplemented diets decreased significantly compared with the diet containing LCT. 3. To determine if endogenous cholecystokinin (CCK) was responsible for the decrease in food intake caused by MCT, birds were injected with the CCK-A receptor antagonist devazepide (DVZ, 1 mg/kg BW) before diet presentation. DVZ had no effect on food intake with either LCT- or MCT-supplemented diets. 4. In experiment 3, chicks were given a choice between either diets containing LCT and C 8, LCT and C 10, or C 8 and C 10 to confirm whether or not the palatability of the diets was influenced by the dietary fat sources. There was no difference in food intake between C 8 and C 10 supplemented diets. However, chicks preferred the LCT-supplemented diet compared with either of the diets containing MCT. PMID- 8467403 TI - Distribution and characteristics of mast cells in the chick ovary. AB - 1. Distribution and characteristics of mast cells have been studied in the ovaries of 5 and 17 week old chickens. 2. Mast cells were mainly present in the stroma, hilum and theca of normal and atretic follicles. No significant age related differences in percentage distribution of mast cells were observed in the stroma and hilar regions of the ovary. However, the percentage of mast cells associated with follicles in both age groups was significantly less compared to stromal and hilar regions. 3. The number of mast cells present in the theca of normal and atretic follicles of stage 301 to 500 microns increased significantly compared to the preceding stages in 17-week old chicken ovaries. Moreover, the number of mast cells associated with the follicles of this stage in 17-week old chick ovaries was also higher compared to 5-week old chicken ovaries. 4. The mast cells showing variable shapes were divided into two types: compact and degranulating. More degranulating mast cells were observed in the 17-week old chicken ovary compared to those observed at 5-weeks. PMID- 8467404 TI - Someone's precious child. PMID- 8467405 TI - Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis. AB - Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1: -3SD deformations only; group 2: one -4SD deformation; group 3: two-four -4SD deformations; and group 4: 5 or more -4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20-40 years) and 109 postmenopausal normal women (average age 64, range 60-70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm2 (P < 0.01) and Ward's triangle 0.059 g/cm2 (P < 0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this cross-sectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures. PMID- 8467406 TI - Fracture of the distal forearm as a forecaster of subsequent hip fracture: a population-based cohort study with 24 years of follow-up. AB - OBJECTIVE: To determine the long-term risk of hip fracture following fracture of the distal forearm. DESIGN: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. FRACTURE COHORT: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period, 1968-1972, in all 1,126 women and 212 men. CONTROL COHORT: An equal number of population-based, age- and sex matched control persons selected from a population register. MEASUREMENTS: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. RESULTS: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. CONCLUSIONS: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered. PMID- 8467407 TI - Videodensitometry of osteons in females with femoral neck fractures. AB - The medial femoral cortices of 10 females with femoral neck fractures and 10 age matched female autopsy cases were studied using computer-assisted videodensitometry. Radiographic mineral density was determined using the calibration method described by Martin et al. [20]. Measurements were made of porosity, osteon and haversian canal dimensions, and of interstitial and osteon mineral density across the cortical wall of the orthopedic calcar region. There were no differences between the fracture and nonfracture groups in the overall mean mineral density of the bone averaged over the microstructure, excluding pore space, or in the interstitial bone mineral density. The porosity in the fracture group was greater than in the autopsy group, especially in the periosteal region, where the porosity was 2.4 times greater and where there were also 27% fewer osteons per unit area than in the autopsy group (P < 0.05). Mean osteon mineral density was 2.5% higher in the fracture group (P < 0.05) compared with the autopsy group in the endosteal region, and 4% higher in the periosteal region. Osteon and haversian canal areas were also larger in the fracture group, especially in the middle region of the cortical wall (17% and 23%, respectively, P < 0.05). PMID- 8467408 TI - Distribution of fluoride in cortical bone of human rib. AB - We describe a detailed study of fluoride distribution with age in the human cortical rib bone. Human ribs were obtained from 110 subjects (M:68, F;42) aged 20-93 years. The fluoride distribution from the periosteal to endosteal surfaces of the ribs was determined by sampling each specimen using an abrasive micro sampling technique, and the samples were analyzed using the fluoride electrode, as described by Weatherell et al. [1]. The concentration of fluoride was highest in the periosteal region, decreased gradually towards the interior of the tissue where the concentration of fluoride tended toward the plateau, and then rose again towards the endosteal surface. Patterns of fluoride distribution changed with age, and the difference between periosteal and endosteal fluoride levels increased with age. Although average fluoride concentrations increased with age in both sexes, there was a significant difference between males and females at the age of about 55 years (P < 0.05). PMID- 8467409 TI - Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation. AB - The objective of this study was to evaluate the effects of a long-term, low calcium diet on fetal calcium metabolism and fetal skeleton development in ewes. Eleven pregnant sheep were assigned to two groups, fed either a diet low in calcium (0.26% total dry matter) or normal in calcium (0.8% total dry matter) for 2 months, starting at 60 days gestational age. The ewes fed the low calcium diet showed lower plasma levels of calcium and higher plasma levels of hydroxyproline, parathyroid hormone, and 1,25(OH)2D compared with the ewes fed the normal calcium diet. There were no differences in these variables between the two groups of fetuses. These observations suggest that the plasma components of calcium homeostasis measured in the fetal lamb in the present study are independent of the ewe and are not significantly affected by the presence of lowered maternal calcium for many weeks during pregnancy. Despite the ability of the fetus of the ewe on the low calcium diet to maintain relatively normal circulating plasma components of calcium homeostasis, long-term maternal hypocalcemia delayed fetal skeletal ossification as shown by histological examination of the fetal humerus. The fetal humerus from low calcium-fed ewes showed a lower proportion of bone versus cartilage (45.6 +/- 5.9 versus 57.4 +/- 4.6%, mean +/- SD) lower ash content (15.4 +/- 1.5 versus 17.4 +/- 1.0%), and lower specific gravity (1.19 +/- 0.2 versus 1.22 +/- 0.02) (P < 0.05) than the humerus from fetuses of normal calcium-fed ewes. This study shows that the long-term calcium intake of the ewe does affect fetal skeletal development, despite a lack of observable effects on fetal plasma concentrations of calcium or known calcium regulating hormones such as 1,25(OH)2D or parathyroid hormone. PMID- 8467410 TI - Insulin enhances the growth of cartilage in organ and tissue cultures of mouse neonatal mandibular condyle. AB - Condylar cartilages were cultured in the form of organ cultures on top of collagen sponges in medium containing 2% fetal calf serum and were treated with 3.5-350 nM insulin for 6 days. Doses of 175 nM of insulin caused a marked increase (+96%) in DNA synthesis and in proteoglycan production (+74%), features that manifested themselves structurally by a 60% increase in overall size of the cultured explants. Using a tissue culture system comprised of cartilage progenitor cells, insulin was found to enhance the differentiation of the progenitor cells so that by 6 days in culture an appreciable nodule of differentiated chondrocytes developed. The latter was surrounded by perichondrial cells whereas the extracellular matrix within the newly formed, insulin-induced, nodule reacted positively for cartilage-specific antigens (type II collagen and bone sialoprotein). It is suggested that insulin induces a direct stimulatory effect on progenitor cell proliferation, cartilage differentiation, and extracellular matrix deposition. PMID- 8467411 TI - Impaired duodenal response to short-term dietary calcium restriction in adolescent spontaneously hypertensive rats. AB - The response pattern of plasma calcitriol level and related intestinal adaptation to short-term moderate calcium (Ca) restriction was examined in adolescent male, spontaneously hypertensive rats (SHR) and normotensive WKY control rats. Twelve week-old SHR and WKY fed a low (0.1%) Ca diet for 3, 6, or 12 days were compared with rats of either strain fed a normal (1.0%) Ca diet. Plasma calcitriol response was measured and duodenal adaptation to Ca restriction was investigated by evaluating active Ca transport, calbindin-D9K (CaBP9K) protein, CaBP9K mRNA, and alkaline phosphatase activity (ALP). Under the normal Ca diet, no significant difference between strains was observed for all five parameters. In response to the low Ca diet, the SHR and WKY showed a similar increase (nearly 50%) in plasma calcitriol, starting at day 3 of this diet. However, only the WKY displayed the expected duodenal adaptation: active Ca transport increased at day 6 and CaBP9K as well as ALP increased at day 3 of the low Ca diet. The stimulation of the latter three parameters was maintained until day 12 of Ca restriction. Moreover, CaBP9K mRNA was increased in WKY after 3 days of Ca restriction. In contrast, the SHR had either no or only a minor increase of duodenal parameters in response to Ca restriction. Finally, a significant and positive correlation between Ca transport and plasma calcitriol and between Ca transport and CaBP9K was found in WKY but not in SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467412 TI - Scanning electron microscopy of final enamel formation in rat mandibular incisors following single injections of 1-hydroxyethylidene-1,1-bisphosphonate. AB - A single, high dose of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) results in three different types of lesions along the enamel surface of the rat incisor, one of which is seen as a "bright band" crossing the final enamel surface in the scanning electron microscope (SEM). The present study presents the structural surface features of final enamel formation and its subsequent maturation in normal and HEBP-exposed rats. The position of the bright band is examined in relation to where the Tomes processes pits disappear (DTPP), where the boundary between "light" and "dark" enamel (LDB) as seen by SEM is located, and in particular, where the so-called opaque boundary (OB) is positioned. Groups of rats were given a subcutaneous dose of 0, 5, or 10 mg P/kg body wt of HEBP and killed at intervals of either 12 hours or 2 or 9 days. The mandibular incisors were processed for SEM after enzymatic digestion of enamel organ remains. Enamel surface nodules, 100-300 nm in diameter and composed of smaller units, were evident at the start of final enamel formation which was defined as the area from DTPP to LDB. With increasing maturation, the nodules merged to form a smooth surface. In HEBP-treated animals, growth and merging of these surface nodules became arrested at the time of injection resulting in an irreversible "porous" stage corresponding to that part of the surface enamel. This area--the bright band--developed corresponding to the start of the area of final enamel formation and was subsequently carried incisally during the eruption of the incisor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467413 TI - Detection of collagenase mRNA in odontoclasts of bovine root-resorbing tissue by in situ hybridization. AB - The odontoclast, which is morphologically similar to osteoclast, is thought to play a major role in root resorption of deciduous teeth. High collagenolytic activity has been detected in the root resorbing tissue. In order to identify collagenase-producing cells and the role of collagenase in root resorption of deciduous tooth, in situ hybridization of collagenase mRNA in bovine root resorbing tissue sections was performed using a digoxigenin-labeled, nonradioactive RNA probe. Collagenase mRNA expression was clearly observed in odontoclasts in addition to the macrophages, fibroblasts, odontoblasts, and cementoblasts. Multinuclear odontoclasts showed intense tartrate-resistant acid phosphatase (TRAP) activity. We also examined interleukin-1 (IL-1) mRNA expression in the root-resorbing tissue by in situ hybridization. IL-1 transcripts were found to be expressed in odontoclasts, fibroblasts, and macrophages suggesting that IL-1 might be an important factor for promoting root resorption. These results suggest that the collagenase produced by odontoclasts may play a key role in dentin collagen degradation in root resorption. PMID- 8467414 TI - Biochemical markers of nutrition in osteoporosis. AB - Thirty-six women with vertebral osteoporosis showed significantly decreased levels of biochemical markers of nutrition, transferrin (P < 0.001), prealbumin (P < 0.001), retinol binding-protein (P < 0.001), and fibronectin (P < 0.001), compared with 40 healthy women of similar age. Multiple regression analysis showed a significant (R2 = 0.509; P = 0.0068) correlation between bone mineral content and biochemical markers of nutrition in the osteoporotic patients but not in the control group. These data suggest that postmenopausal osteoporosis may be associated with a nutritional deficiency. PMID- 8467415 TI - Antigen-specific recognition by class I major histocompatibility complex restricted T cells and activation of CD8+ memory cytotoxic T cells. PMID- 8467416 TI - A review of the microbiological quality of bottled water sold in Canada. Part 2. The need for more stringent standards and regulations. PMID- 8467417 TI - Purification and partial characterization of a bacteriocin isolated from Bacteroides ovatus H47. AB - A new intracellular bacteriocin isolated from a human fecal strain of Bacteroides ovatus was partially purified through ammonium sulfate precipitation, ion exchange chromatography, gel filtration, and preparative polyacrylamide gel electrophoresis (PAGE). The bacteriocin is stable at a pH range of 3-10, at 60 degrees C for 24 h, and at -70 degrees C for 6 months. It is inactivated by proteolytic enzymes. The molecular weight, estimated by sodium dodecyl sulfate- PAGE, is 78 kDa. Fifty strains of the Bacteroides fragilis group were isolated from fecal samples, and 41 of the isolates were shown to produce an antagonistic substance against at least 1 indicator strain. Iso-, auto-, and hetero antagonisms were observed. PMID- 8467418 TI - 1,3,5-Trihydroxybenzene biodegradation by Rhodococcus sp. BPG-8. AB - The metabolic pathway used by Rhodococcus sp. BPG-8 isolated from oil-rich soil in Newfoundland for the degradation of 1,3,5-trihydroxybenzene (phloroglucinol) as a sole source of carbon and energy was determined. Culture filtrates of cells grown on phloroglucinol detected 1,2,3,5-tetrahydroxybenzene when extracted and analyzed using gas chromatography--mass spectrometry, thin-layer chromatography, and ultraviolet spectrophotometry. Nonaromatics were either derivatized with 2,4 dinitrophenylhydrazine and compared against authentic standards by the above methods, or detected by chemical and enzymatic methods. Extracts of cells grown on phloroglucinol contained phloroglucinol hydroxylase activity, and a dioxygenase that carried out ortho-cleavage of 1,2,3,5-tetrahydroxybenzene. The extract also showed inducible activity for further metabolism of acetopyruvate leading to accumulation of formate in the supernatant. A tentative degradative pathway for phloroglucinol by Rhodococcus sp. BPG--8 is proposed. PMID- 8467419 TI - Measurement of the intracellular pH of Propionibacterium acnes: comparison between the fluorescent probe BCECF and 31P-NMR spectroscopy. AB - The intracellular pH of the Gram-positive skin bacterium Propionibacterium acnes was determined using the pH-sensitive fluorescent probe 2',7'-bis-(2 carboxyethyl)-5-(and-6)carboxyfluorescein (BCECF). The probe was introduced into the bacteria using the membrane-permeable acetoxymethyl ester BCECF-AM. The intracellular pH of the bacteria was determined by establishing a relation between the fluorescence ratio 505/450 and pH using the ionophore nigericin. To verify the intracellular pH determined using BCECF, the results were compared with those obtained using 31P-NMR spectroscopy. The effects of different external pH values and glucose addition upon the intracellular pH were examined using BCECF and 31P-NMR. Good correlation was obtained between the two techniques. Propionibacterium acnes maintained a pH gradient, inside alkaline, in the external pH range 5.0-7.4, which inverted when the pH was > 7.5. At external pH > or equal to 8.5, the intracellular pH was close to the external pH. Glucose exposure did not affect the intracellular pH. Rapid, transient intracellular acidification and alkalinization brought about using NaHCO3 and NH4Cl, respectively, could be detected using BCECF. A limitation encountered when using BCECF was BCECF leakage, which could significantly affect the results if not taken into account. PMID- 8467420 TI - Purification and properties of mercuric reductase from Yersinia enterocolitica 138A14. AB - A mercuric ion-reducing flavoprotein was purified from Yersinia enterocolitica 138A14 using dye matrix affinity chromatography. The purified enzyme had a characteristic absorption spectrum similar to those of flavin compounds, and FAD was detected as a part of the purified enzyme by thin-layer chromatography. Freshly purified preparations of the enzyme showed a single band on SDS polyacrylamide gel electrophoresis with a molecular weight of 70,000. The isolated enzyme had a molecular weight of about 200,000 as determined by gel filtration and disc gel electrophoresis. These results suggest an apparently trimeric structure of the enzyme. Dithiothreitol treatment disrupted the trimer into a dimeric structure of 140,000. Along with ageing, as well as limited proteolytic digestion, the enzyme evolved to give a dimeric molecule of 105,000 composed of two identical subunits of 52,000. The combination of the purified enzyme with HgCl2, or unexpectedly with merthiolate, oxidised the NADPH, which was followed spectrophotometrically. The Km for HgCl2 was dependent on the concentration of exogenous thiol compounds. A comparison of physical properties as well as kinetic characteristics indicated that the enzyme from Y. enterocolitica 138A14 is similar to mercuric reductases isolated from other mercury-resistant bacteria. PMID- 8467421 TI - Degradation of acrylamide by immobilized cells of a Pseudomonas sp. and Xanthomonas maltophilia. AB - Two bacterial isolates capable of utilizing acrylamide as the sole source of carbon and nitrogen were isolated from herbicide-contaminated soil samples and identified as Pseudomonas sp. and Xanthomonas maltophilia. Batch cultures of Pseudomonas sp. and X. maltophilia completely degraded 62.8 mM acrylamide to acrylic acid and ammonia in 24 and 48 h, respectively. Pseudomonas sp. and X. maltophilia, when immobilized in calcium alginate, markedly increased the rate of degradation of acrylamide over batch cultures. Cells of the isolates immobilized in calcium alginate degraded acrylamide to acrylic acid and ammonia in less than 6 h. Initial metabolism of acrylamide by immobilized cells of Pseudomonas sp. followed by inoculation with nonimmobilized cells after 6 h totally removed acrylamide and its metabolites in 72 h. A similar procedure with X. maltophilia resulted in the total metabolism of acrylamide in 96 h. An inducible, intracellular amidase was responsible for the hydrolysis of acrylamide to acrylic acid and ammonia. The specific activity of Pseudomonas sp. amidase was higher than the specific activity of X. maltophilia amidase. PMID- 8467422 TI - Levels of small molecules in dormant spores of Sporosarcina species and comparison with levels in spores of Bacillus and Clostridium species. AB - Dormant spores of Sporosarcina halophila and Sporosarcina ureae contained no detectable ATP, significant levels of ADP, even higher levels of AMP, and a large pool of 3-phosphoglyceric acid, similar to what is found in dormant spores of Bacillus and Clostridium species. Sporosarcina halophila and S. ureae spores also contained significant pools of free amino acids, in particular glutamic acid, as in the case with spores of Bacillus but not Clostridium species. Levels of monovalent and divalent inorganic cations were comparable in spores of Sporosarcina, Clostridium, and Bacillus species, and cation levels in spores of the slight halophile S. halophila were similar to those in S. ureae spores. These data suggest that levels of small molecules are generally similar in spores of all Gram-positive organisms, and further suggest that these levels reflect fundamental and conserved features of the sporulation process and dormant spores in these organisms. The data are also consistent with the proposed close evolutionary relationship between Bacillus and Sporosarcina species. PMID- 8467423 TI - Instability of the production of avermectins, sporulation, and pigmentation in Streptomyces avermitilis. AB - Production of avermectins, sporulation ability, and colony pigmentation were followed in Streptomyces avermitilis C-18/6 cultures during serial transfer (for eight subcultures) in four different liquid media. These phenotypes were found to be unstable and independent of each other. A procedure was established whereby depressed avermectin production could be reversed but the degree of reversion was dependent on the history of the isolate, i.e., the type of medium used. The presence of isoleucine as the sole N source caused an immediate loss of avermectin production and this could not be reversed. PMID- 8467424 TI - Epidemiology of multiple sclerosis: a critical overview. AB - The decisive conclusions to be drawn from the available epidemiological data, mostly geography and prevalence, of MS are: (1) a north-south (as well as west east in the United States) gradient exists independent of genetic/racial factors; (2) major differences in prevalence occur in the absence of latitude differences; (3) individuals from the same ethnic derivation have either similar prevalence rates or very different prevalence rates in widely separated geographical areas and (4) specific resistant isolates are shown to exist regardless of latitude. Existing information leads to the almost inescapable conclusion that the epidemiology of MS cannot be explained by any single known environmental or genetic factor(s) in isolation. A combination of a heterogeneous distribution of both genetic and environmental factors appears to be required to explain the available data on MS. PMID- 8467425 TI - Penfield Lecture. A quarter century's experience with intraoperative nerve action potential recording. AB - The rationale, basic considerations, and technique of intraoperative nerve action potential (NAP) recording have been reviewed. Experience using this technique in several thousand patients over a 25 year period has been summarized. The most frequent serious nerve injury is one that leaves it in continuity. Resection of such a lesion that is regenerating does the patient a great disservice as does exploration without repair of one with little or no potential for useful spontaneous recovery. The frequency of lesions in continuity as well as the difficulties in evaluating them in the early months by electromyography let alone by surgical inspection has led to the development of intraoperative NAP recording. Where neurolysis was based on a recordable NAP across a lesion in continuity, 93% recovered good function. Where resection of the lesion was based on absence of an NAP, the injury was, without exception, neurotmetic and/or one with poor potential for useful recovery without repair. Some lesions had an NAP across their lesion but a portion of the cross-sectional area appeared more seriously injured. By use of NAP recordings, a split repair was done and usually with good results. PMID- 8467426 TI - Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross linked hemoglobin on brain injury and edema. AB - The effect of hemodilution, with alpha-alpha cross-linked hemoglobin (DCLHb), on brain injury and edema was assessed after temporary middle cerebral artery occlusion in rats. Injury was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC) stain and edema by microgravimety. Part A: DCLHb was given to maintain one of the following hematocrits (Hct) and normotension: 1) 45/Hct, 2) 30/Hct, 3) 16/Hct, or 4) 9/Hct. Brain injury (% of ischemic hemisphere, mean +/- SD) was less in the 30/Hct group (31 +/- 4) versus the 45/Hct group (42 +/- 5); and in the 16/Hct (20 +/- 3) and 9/Hct (19 +/- 4) groups versus the 45/Hct and 30/Hct groups. Edema was less in the hemodiluted groups versus the 45/Hct group. Part B: DCLHb was given to maintain one of the following hematocrits and hyper (HTN)-or normotension (Norm): 1) 45/Norm, 2) 30/Norm, 3) 30/HTN, 4) 16/Norm, or 5) 16/HTN. In hematocrit matched groups hypertension decreased brain injury (30/HTN-24 +/- 2 < 30/Norm-34 +/- 4; and 16/HTN-17 +/- 3 < 16/Norm-24 +/- 4). Edema was not effected by hypertension. These results suggest that hemodilution with DCLHb decreases focal ischemic injury, and is most effective when given in a manner that induces hypertension. PMID- 8467427 TI - Failure of iron chelators to protect against cerebral infarction in hypoxia ischemia. AB - In this study the ability of iron chelators to attenuate hypoxic-ischemic brain damage was assessed in hyperglycemic rats that were exposed to 1% carbon monoxide and right carotid occlusion. The animals received deferoxamine (50 mg/kg), manganese-deferoxamine (50 mg/kg) or vehicle i.p. 0.5 h prior to hypoxemic ischemic exposure and at 0.5, 3 and 24 h post-exposure; with subsequent histological examination of the brain at 7 days recovery. The area of cerebral infarction was measured at three levels using video imaging methods. The mean percentage of total hemisphere that was infarcted in the three groups was: vehicle--28.5 +/- 5.0; deferoxamine--31.7 +/- 12.1; and manganese deferoxamine- 30.6 +/- 6.8 (p-n.s.). The results as obtained in this preliminary study indicate that aggressive pre- and post-treatment with iron chelators has no ability to attenuate cerebral infarction in this model. PMID- 8467428 TI - Single-blind study of dystrophin staining in carriers of Duchenne muscular dystrophy. AB - A single-blind study of dystrophin staining in skeletal muscle was performed in 13 biopsies from carriers of Duchenne Muscular Dystrophy (DMD) and controls. The results indicate that immunohistochemical analysis of dystrophin staining is a valuable diagnostic test for DMD carriers when DNA for testing is unavailable from critical family members or is uninformative, when creatine kinase (CK) values are conflicting or when CK values must be used in isolation. PMID- 8467429 TI - Detection of Lewy bodies in Trisomy 21 (Down's syndrome). AB - The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropathological diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a clinico-neuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neurohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression. PMID- 8467430 TI - A double-blind cross-over trial of amantadine hydrochloride in Friedreich's ataxia. AB - We performed a double-blind cross-over study with amantadine hydrochloride in 12 patients with Friedreich's disease and 2 with autosomal dominant cerebellar ataxia. Patients were randomly assigned to a placebo-amantadine or amantadine placebo sequence. The interval between the treatments was two weeks. Patients were graded according to a functional ataxia scoring scale and videotaped in basal conditions and 90 min after a single oral dose of 100 mg amantadine or placebo. Three evaluators independently scored the videotapes. Statistical analysis showed no significant effect of amantadine in Friedreich's disease. PMID- 8467431 TI - Cervical disc herniation presenting with chest wall pain. AB - This report highlights the clinical features of two patients who presented with severe neuropathic chest wall pain caused by herniated C6-7 disc, and speculates on the pathophysiology of this syndrome. Worsening of symptoms with neck movement helped localize the process as cervical spine rather than plexus in origin. Both patients had herniated C6-7 disc material compressing the spinal cord and C7 nerve root, and neurological symptoms resolved promptly following surgery. Neuropathic chest wall pain should alert the clinician to consider the diagnosis of cervical disc herniation and prompt definitive imaging of the cervical spine by myelography or magnetic resonance imaging (MRI). PMID- 8467432 TI - Horner's syndrome secondary to angiogram negative, subadventitial carotid artery dissection. AB - A 59-year-old man presented with the acute onset of paresthesias and pain in the left neck, face, and forehead. On subsequent investigation he was found to have a subadventitial type of carotid artery dissection, producing an ipsilateral Horner's syndrome with normal carotid angiography. MRI imaging of the neck structures, using fat saturation technique, showed the subadventitial dissection, sparing the vessel lumen. MRI offers a non-invasive method of diagnosis and follow-up for carotid artery dissection. PMID- 8467433 TI - Epineurial peptides: a role in neuropathic pain? AB - Neuropathic pain is not well understood. Although central dorsal horn remodelling is likely important in maintaining chronic neuropathic pain, afferent activity from injured nerves or ganglia may initiate these changes. It is suggested, in this review that the peripheral nerve trunk is capable of sustaining a "flare" response as observed in injured skin and other tissues. The injury response may be associated with local vasodilatation, plasma extravasation and the generation of painful local afferent activity sustained by locally originating peptidergic fibers (nervi nervorum). These fibers contain substance P, calcitonin gene related peptide and other peptides that have been linked to nociceptive transmission. Manipulation of the local injury response of the nerve trunk by pharmacologic means may provide one strategy in the treatment of neuropathic pain. PMID- 8467435 TI - Epidemiology of pathological gambling in Edmonton. AB - Thirty lifetime pathological gamblers (DSM-III, no exclusion criteria) were identified when 7,214 randomly selected household residents of Edmonton were interviewed by trained lay interviewers using the Diagnostic Interview Schedule. The lifelong prevalence of pathological gambling was 0.42% (ratio of males to females 3:1). The peak age of onset was 25 to 29 years. Gamblers had high rates of comorbidity with other psychiatric disorders. They were likely to have made suicide attempts (13.3%), to have been convicted of offences (26.7%), to be spouse and child abusers (23.3% and 16.7% respectively) and to have spent long periods unemployed (40%). In addition, 80% had trouble at home or work because of gambling, and 60% borrowed or stole to gamble. PMID- 8467434 TI - The reduction of violence in a chronic psychiatric inpatient group: a social technique. AB - A group of 72 chronic psychiatric inpatients comprised of the most violent and the least violent patients on a long term unit were studied prospectively for one year. The impact of increasing the doctor-patient contact in the second six months on the frequency of violent episodes was studied. The contact was brief and structured. Changes in staff, medication and the number of family visits were not found to be significant. The increased in contact seemed to have been highly significant. Violent episodes were reduced by 82% and had completely ceased by the last month of the study. PMID- 8467436 TI - Dimenhydrinate abuse among adolescents. AB - Dimenhydrinate may be a relatively common yet unrecognized substance of abuse among adolescents. Abuse of this drug may present as a psychiatric syndrome, particularly depression. Three cases are presented which illustrate this relationship. A review of the literature is presented and suggestions are made for identifying adolescents who abuse dimenhydrinate. PMID- 8467437 TI - [Influence of mass media on mental health]. AB - The author summarizes different research findings which have evaluated the influence of the media on the mental health of children, adolescents and adults. After this review of the literature, strategies are proposed to improve the promotion of mental health in the media. Also the importance of collaboration between health professionals and broadcasters in this process is highlighted. Concrete examples are reported such as the communication programs which have been developed by the Quebec Mental Illness Foundation and the Quebec Psychiatrists' Association. PMID- 8467438 TI - Changes to the Criminal Code provisions for mentally disordered offenders and their implications for Canadian psychiatry. AB - Bill C-30, implemented in February 1992, made a number of significant changes to the Criminal Code provisions concerning the assessment, treatment and disposition of mentally disordered persons charged with a crime, including persons considered to be unfit to stand trial or pleading insanity. The changes deal mainly with procedural law and the civil rights of persons being assessed or held in custody, and put limits on where, how long and for what purpose persons may be detained. The new law abolishes the automatic, indeterminate detention of persons found unfit to stand trial or not criminally responsible on account of mental disorder. The changes may mean that the forensic psychiatric route is now a more "attractive option" for defendants. The new law may create administrative problems for clinicians by leading to increased requests for psychiatric assessments while at the same time constraining the assessment process. PMID- 8467439 TI - [Cardiovascular pathology and panic disorder]. AB - The relationship between anxiety and cardiovascular function and symptoms has long been of interest, culminating in the recent emphasis on the modulation of cardiovascular response in patients with panic disorder. The relationship between panic disorder and mitral valve prolapse remains controversial. Panic disorder appears to be significantly associated with increased incidence of cardiovascular morbidity. The detection and treatment of panic disorder in patients with cardiovascular risk or diseases could have an important impact on prognosis and quality of life of the patients. PMID- 8467440 TI - Treatment of rapid cycling bipolar disorder with combination therapy of valproate and lithium. AB - Over the past two decades there has been a great deal of interest in the use of anticonvulsants to treat a variety of primary psychiatric disorders. Valproate, one such anticonvulsant, has been found to be effective in the treatment of acute mania, mixed states and rapid cycling disorders. This paper presents the results of an open study with combination therapy of valproate and lithium in a series of nine patients (mean age = 50 years). These patients had previously been treated with various psychotropic agents, including a combination of carbamazepine and lithium. All but one patient showed marked or moderate improvement in their condition. Of particular interest was the observation that in three patients there was evidence of augmentation between valproate and lithium during the depressed phase of their illness. There was significant improvement in their depression within 24 to 48 hours of the addition of lithium to valproate. The combination therapy was very well-tolerated. It is concluded that valproate and lithium combination therapy provides a safe and effective alternative for the treatment of rapid cycling variant of bipolar illness. PMID- 8467441 TI - A checklist for evaluating the usefulness of rating scales. AB - Rating scales of various sorts are very useful for both clinical and research purposes. However, they vary greatly regarding their reliability, validity, and utility. This article provides a guide for people who need to evaluate scales, either to incorporate them into their own research or clinical activities, or to determine if the results of studies which use scales are meaningful. The different types of reliability and validity are discussed and guidelines are offered to evaluate how well these were assessed. Finally, other aspects of scales which can affect their usefulness, such as completion time, training, and scoring ease, are discussed. PMID- 8467442 TI - Phantom limb in schizophrenia and the central hypothesis. PMID- 8467444 TI - Therapy of the absurd. PMID- 8467443 TI - Pimozide-responsive monosymptomatic hypochondriacal psychosis in an adolescent. PMID- 8467445 TI - Depression versus dementia. PMID- 8467446 TI - Benzodiazepines and the ear--tinnitus, hallucinations and schizophrenia. PMID- 8467447 TI - Training psychiatric residents to work with primary care physicians: results of a national survey. AB - To assess the preparation of residents in psychiatry for working with family physicians, a questionnaire was sent to the directors of Canada's 16 psychiatry residency programs. The results of the study are presented with recommendations for improving this aspect of training. PMID- 8467448 TI - Tarasoff in the Canadian context: Wenden and the duty to protect. AB - The precedent-setting 1976 US court decision of Tarasoff v. Regents of the University of California established a "duty to protect" whereby psychotherapists are held responsible to protect the potential victims of their clients' violent behaviour. The purpose of this article is to review and discuss this duty in the context of Canadian law and the 1991 Alberta court decision of Wenden v. Trikha, Royal Alexandra Hospital and Yaltho. The current Canadian interpretation of the duty to protect and guidelines for avoiding such liability are presented. PMID- 8467449 TI - Geriatric psychiatry: training guidelines and their application. Section on Geriatric Psychiatry of the Canadian Psychiatric Association. AB - Geriatric psychiatry is now a mandatory part of psychiatric residency education in Canada. Educational requirements in geriatric psychiatry were updated by the Royal College of Physicians and Surgeons of Canada in 1988, and guidelines were developed in more detail in 1989 by the Section on Geriatric Psychiatry of the Canadian Psychiatric Association (CPA). These guidelines are presented here together with a survey, conducted in the fall of 1991, of all 16 Canadian psychiatry residency programs. Thirteen of the training centres now require residents to have a formal rotation in geriatric psychiatry, generally three months in length. Residents are exposed to elderly patients in other services, such as consultation/liaison, but these services may not include formal teaching in geriatric psychiatry. Most programs have a seminar series in geriatric psychiatry and have training guidelines similar to those of the CPA. However, it is not clear how closely these are being followed, since it was felt in almost one-third of all programs that there was an insufficient number of teachers to fulfill the training requirements. In addition, a number of training directors felt that the objectives were too comprehensive to be met in the three month period. Earlier studies in the field are reviewed, implications of the current findings are discussed, and suggestions are made for further research. PMID- 8467450 TI - [A crisis intervention service in an outpatient psychiatric clinic of a general hospital: function and clientele]. AB - The authors describe an external crisis intervention service in a general hospital. This service is intended for a clientele presenting acute mental health problems, referred, in the majority of cases, from the emergency department. They present demographic data, diagnostic data, data on the factors precipitating the crises and data which can be used to qualify and quantify the clientele. In addition, they describe the therapeutic approach and the treatment philosophy, the number of follow-up sessions, and the guidance provided to the clientele after follow-up. Finally, the authors suggest prerequisites considered essential to the effective operation of a crisis intervention module in an external psychiatric clinic. PMID- 8467451 TI - Carcinoma of the parotid gland. Analysis of treatment results and patterns of failure after combined surgery and radiation therapy. AB - BACKGROUND: The authors retrospectively studied 62 patients with malignant parotid tumors, treated by combined surgery and radiation therapy between 1975 and 1989. No patients were lost to follow-up, and all living patients were interviewed. The median follow-up time was 66 months. RESULTS: Among the 62 patients, there were five isolated local failures. Distant failure was observed in 11 patients. Neck failure was uncommon except in patients with advanced neck disease on presentation. The actuarial 5-year and 10-year local control rates were 95% and 84%, respectively. The corresponding actuarial disease-free survival (DFS) rates were 77% and 65%, respectively. Patients with larger tumors, recurrent disease, or involvement of the facial nerve tended to have lower DFS rates. No statistically significant differences were observed for patients treated with once-daily versus twice-daily radiation therapy fractionation schemes. CONCLUSIONS: Treatment was well tolerated, and severe treatment sequelae were uncommon. In summary, surgery in combination with radiation therapy is highly efficacious in controlling malignant tumors of the parotid gland. PMID- 8467452 TI - Carboplatin and etoposide in advanced colorectal carcinoma. A phase II study. AB - BACKGROUND: For advanced colorectal carcinoma, 5-fluorouracil (5-FU)-leucovorin is the best therapy available. To improve results, a variety of drugs were added, including cisplatin (CDDP), sometimes with controversial results. The combination of CDDP and etoposide (VP-16) has shown synergistic activity in other settings. Although VP-16 alone is considered rather inactive in colorectal carcinoma, the authors believed it was appropriate to evaluate the combination of VP-16 and carboplatin (CBDCA) in this disease because the newer platinum analogue CBDCA has more limited side effects than the parent compound. METHODS: Twenty-eight patients with advanced colorectal carcinoma were treated with CBDCA (200 mg/m2, days 1-3) and VP-16 (100 mg/m2, days 1-5). Cycles were repeated every 4 weeks. All patients received at least two cycles (median, six cycles; range, two to eight cycles). RESULTS: There were three complete responses and four partial responses. The median duration of response was 35 weeks (range, 25-84 weeks). The median time to tumor progression was 23 weeks (range, 9-84 weeks). The median survival time was 49 weeks (range, 9-151+ weeks). Toxic effects generally were assessed as mild, with no Grade 4 (Eastern Cooperative Oncology Group classification) toxic effects observed during this study. CONCLUSIONS: Response rate and toxic effects observed during this study warrant additional studies comparing this regimen with 5-FU-based regimens in advanced colorectal carcinoma. PMID- 8467453 TI - Analysis of the results of combined therapy for maxillary carcinoma. AB - BACKGROUND: Maxillary sinus carcinomas usually are locally advanced. A wide variety of modalities, including surgery, radiation therapy, and intraarterial chemotherapy, alone or in combination, have been used. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1972 to 1986, 108 patients with squamous cell carcinoma of the maxillary sinus were treated at the Department of Radiology, University of Tokyo Hospital. From 1972 to 1974 (the first period), the treatment consisted of operation for reduction of tumor volume, daily cleaning of the maxillary antrum, 20 Gy of postoperative radiation therapy, and intraarterial infusion of 1500 mg of 5-fluorouracil (5-FU) and 3000 mg of 5-bromodeoxyuridine (BUdR). From 1975 to 1979 (the second period), the radiation dose was reduced to 10 Gy, and intraarterial infusion of 5-FU and BUdR was not performed. Surgery for reduction of tumor volume and daily cleaning of the antrum played a major role in this period. From 1980 to 1982 (the third period), daily cleaning of the antrum was not performed. Instead, the dose of radiation was increased to 50-60 Gy. From 1983 to 1986 (the fourth period), more extensive surgery to resect the tumor en bloc was introduced. The radiation dose was increased to 70 Gy. Intraarterial infusion of 3750 mg of 5-FU and 120 mg of cisplatin also was administered. RESULTS: The 5-year survival rate was 46% in the first period, 24% in the second period, 7.2% in the third period, and 53% in the fourth period. In the third period, there were more cases in which death resulted from a cause other than local failure, such as distant metastasis, pneumonia, or secondary primary cancer. Since 1984, we planned treatment with computed tomography (CT) and used the linear accelerator with a multileaf collimator to treat patients with an irregular field of irradiation. These have made it possible to administer radiation therapy in doses as high as 70 Gy without severe complications and improve the survival rate, especially for T4 disease. CONCLUSIONS: Radiation plays an important role in sterilizing malignant cells that cannot be removed by operation. The dose of radiation should be determined according to the volume of residual tumor. Careful treatment planning is required to irradiate the tumor adequately and reduce complications. PMID- 8467454 TI - Malignant melanoma in different ethnic groups in Israel. Incidence and biologic behavior. AB - BACKGROUND: The Jewish population of Israel is divided into two ethnic groups: Ashkenazic Jews (AJ) who immigrated from Europe and are fair-skinned, and Sephardic Jews (SJ) who immigrated from the Orient and Africa and who are dark skinned. The biologic behavior of malignant melanoma (MM) in these two groups has not been investigated. METHODS: Three hundred forty-eight of 380 patients with MM, who could be accurately grouped ethnically, constitute this study group. The gender, site and depth of primary tumor, metastatic involvement and survival analysis, including univariate analysis for level of invasion, were examined. RESULTS: Of 348 patients with MM, 285 were AJ and 63 were SJ. The female:male ratio was 2:1 and 0.9:1, for AJ and SJ, respectively (P < 0.05). Lesion site distribution was similar. The lesions were more invasive in SJ, 53% Clark level 4 5 versus 41% in AJ (P < 0.05). The 5-year survival was worse in SJ relative to AJ -50% versus 71% for female patients and 30% versus 62% for male patients--but did not reach statistical significance (NS). The actuarial 10-year survival showed poorer survival for female SJ: 27% versus 67% in female AJ (P < 0.05) and male SJ; 32% versus 65% in male AJ (P < 0.01). For all stage I MM, the actuarial 10 year survival was in male patients 32% versus 79% (P < 0.05), and in female patients, 27% versus 72% (P < 0.05) in SJ and AJ, respectively. For the more invasive lesions (Clark levels 4 and 5), the actuarial 10-year survival was for male patients 19% versus 75% (P < 0.05) and for female patients, 65% versus 67% (NS) in SJ and AJ, respectively. CONCLUSIONS: The dark-skinned SJ tend to have MM less than the fair-skinned AJ, but once MM occurs in SJ, it appears to have a more virulent nature. PMID- 8467455 TI - Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. A report of the Gilda Radner Familial Ovarian Cancer Registry. AB - BACKGROUND: According to previous reports, primary peritoneal carcinoma indistinguishable from primary ovarian adenocarcinoma had developed in five women with a history of familial ovarian cancer who had undergone prophylactic oophorectomy. METHODS: The records from the Gilda Radner Familial Ovarian Cancer Registry were reviewed for instances of prophylactic oophorectomy and cases of primary peritoneal carcinoma occurring after prophylactic oophorectomy. RESULTS: From 1981 through July 1992, the Gilda Radner Familial Ovarian Cancer Registry accessioned 931 families (a total of 2221 cases of familial ovarian cancer). Currently, 324 women in these families have undergone prophylactic oophorectomy as a preventive measure against the subsequent development of ovarian cancer. Primary peritoneal carcinoma indistinguishable histologically from primary ovarian adenocarcinoma has developed in six of these women 1-27 years after prophylactic oophorectomy. CONCLUSIONS: Based on this finding and other reports of such primary peritoneal carcinoma, a prospective international study is planned. This study will compare the incidence of peritoneal carcinoma in first- or second-degree relatives who underwent prophylactic oophorectomy because of a family history of ovarian cancer with that of those who did not undergo prophylactic oophorectomy. PMID- 8467456 TI - Variation in body fat distribution and breast cancer risk in the families of patients with breast cancer and control families. AB - BACKGROUND: The pattern of body fat distribution in women has been correlated with the risk of developing breast and endometrial cancer. The authors determined whether body fat distribution varied between first-degree relatives of patients with breast cancer and in cancer-free families by comparing the body fat distribution of first-degree relatives of patients with breast cancer with age and Quetelet Index-matched controls. METHODS: Fifty-six first-degree relatives of newly diagnosed patients with breast cancer were compared with 56 controls (non cancer family members) matched for age and Quetelet Index and were studied for variation in body fat distribution. Anthropometric measurements were taken for the abdomen, thigh, suprailiac, subscapular, biceps, and triceps skinfold thickness; waist and hip circumference; weight; and height. The distribution of body measurements and derived ratios in both case and control family members were compared using the Student t test. RESULTS: A significant variation in body fat distribution occurred among first-degree relatives in breast cancer and control families. In families with a history of breast cancer, first-degree family members were found to have significantly greater waist:hip ratio (P < 0.001) compared with controls without family history matched for age and Quetelet Index. Other variables indicating upper body fat localization, such as abdomen and suprailiac skinfold were significantly greater in family members of patients with breast cancer compared with controls. CONCLUSIONS: A marked variation occurred in body fat localization among first-degree relatives of patients with breast cancer and in cancer-free families. This finding implies a variation in breast cancer risk in these families. Identifying family members with upper body fat distribution in breast cancer families would allow targeting of these individuals for energetic screening and risk factor reduction interventions. PMID- 8467457 TI - Enhancement of progesterone receptor levels by interferons in AE-7 endometrial cancer cells. AB - BACKGROUND: Interferon (IFN) has been reported to increase hormone receptor expression in breast cancer cells and to sensitize them to antiproliferative hormones. Endometrial cancer cells with high progesterone receptor (PR) level respond better to progesterone therapy than cells with either low or absent PR level. The effect of four different interferons (alpha and beta, both natural [n] and recombinant [r]) on cell proliferation and steroid receptor levels was investigated in the PR positive AE-7 human endometrial cancer cell line over a period of 12 days. METHODS: Cells were exposed to 10,100 and 1000 IU/ml of each IFN either for 3 days or continuously for 12 days. Hormone receptors were determined by the monoclonal enzyme immunoassay. Chemosensitivity was evaluated with the adenosine triphosphate-cell viability assay. RESULTS: AE-7 has a low level of estrogen receptors, which was not significantly affected by IFN exposure. The four IFN showed significantly enhanced PR levels over 12 days in both the 3-day and continuous-exposure experiments. No significant difference of PR enhancement was observed between 3 days and continuous exposure to IFN. This increase of receptors did not appear to be dose related. IFN enhanced PR level to a maximum level of about two times control cells. IFN did not produce significant cytotoxicity. Antiproliferative activity was observed with nIFN beta and rIFN beta at 1000 IU/ml dose in continuous-exposure experiments, which showed survival values of 79% and 69% respectively, compared with control at day 12. CONCLUSIONS: These preliminary data on PR expression modulation support other studies, which have shown that IFN modulate hormone receptor expression and, therefore, may play a role in the treatment of endometrial cancer. PMID- 8467458 TI - Uveal metastasis from prostate carcinoma. AB - BACKGROUND: Although breast and lung cancers account for most metastatic tumors to the uvea, prostate carcinoma metastatic to the uvea is relatively rare. METHODS: The authors reviewed 379 consecutive patients with uveal metastasis referred to the Ocular Oncology Service at the Wills Eye Hospital to determine the frequency of prostate carcinoma as the primary neoplasm. RESULTS: Of 379 consecutive patients with uveal metastasis, the primary tumor was prostate carcinoma in 7 (2% of all patients, 5% of male patients). The mean age at ocular diagnosis was 66 years. In six patients (85%) a prior history of prostate carcinoma was known and the prior history of prostate carcinoma was known and the mean time interval between the diagnosis of the primary tumor and the uveal metastasis was 28 months. All seven patients were found to have active or regressed metastases elsewhere. The choroid was involved in six patients (85%) and the iris in one (15%). Ocular treatment included external-beam radiation therapy in five patients (70%) and episcleral radioactive plaque in two (30%). After a total mean follow-up of 84 months (range, 44-140 months) from the diagnosis of prostate carcinoma, two patients were still alive and five patients have died (mean, 6 months after diagnosis of uveal metastasis). CONCLUSIONS: Prostate carcinoma can metastasize to the uvea and the presence of uveal metastasis is associated with a shorter survival time compared with metastasis to other sites. PMID- 8467459 TI - DNA heterogeneity in prostatic adenocarcinoma. A DNA flow cytometric mapping study with whole organ sections of prostate. AB - BACKGROUND: The degree of DNA heterogeneity varies between tumors arising at different sites. The presence of a significant degree of variability within a given tumor may result in problems in the interpretation of DNA flow cytometric findings. This study evaluated the degree of DNA heterogeneity in prostatic adenocarcinoma. METHODS: A total of 122 3-mm punch biopsy specimens were evaluated from single representative whole organ sections from nine cases of prostate cancer (range, 4-18 samples per case; mean, 12 samples; median, 14 samples). Individual punch biopsy specimens were graded and reviewed to confirm the presence of carcinoma and processed for DNA ploidy analysis. RESULTS: Assessable histograms, defined as having a coefficient of variation of the diploid G0/G1 peak of 7.5% or less, were available for 111 (91%) of the samples. Of the nine cases studied, five (56%) showed heterogeneity in the DNA pattern (diploid plus aneuploid, n = 1; diploid plus tetraploid, n = 2; and diploid plus tetraploid plus aneuploid, n = 2). All four cases having a homogeneous DNA content were DNA diploid in all samples. In those cases with a heterogeneous pattern, the areas having abnormal DNA patterns could not be predicted by histologic pattern or grade. CONCLUSIONS: From this study, the authors conclude that a significant degree of DNA heterogeneity exists within individual cases of prostatic adenocarcinoma, and this may be an important confounding factor in DNA ploidy studies. PMID- 8467460 TI - Common expression of parathyroid hormone-related protein and no correlation of calcium level in renal cell carcinomas. AB - BACKGROUND: Parathyroid hormone-related protein (PTHrP) is the predominant cause of humoral hypercalcemia of malignancy (HHM). METHODS: Using a PTHrP-specific monoclonal antibody (MoAb), 4B3, the authors investigated the immunohistochemical localization of PTHrP in formalin-fixed and paraffin-embedded sections of normal human kidney tissues and tissues from 42 human renal cell carcinomas obtained at operation or autopsy. RESULTS: In normal renal tissues, the distal tubules and collecting ducts showed positive immunostaining. PTHrP was detected in 40 of 42 renal cell carcinoma tissues (95%). Histopathologically, the granular cell subtypes of renal cell carcinomas tended to be more strongly positive than the clear cell subtypes. There was no significant correlation between the level of immunostaining and each patient's serum calcium level. CONCLUSION: PTHrP was commonly observed in renal cell carcinomas, and no significant correlation was seen between the intensity of PTHrP staining and the serum calcium level. PMID- 8467462 TI - Bone tumors other than osteosarcoma after retinoblastoma. AB - BACKGROUND: The most frequent second malignant neoplasm after retinoblastoma is osteosarcoma, which may be associated with radiation therapy or arise de novo in patients with bilateral retinoblastoma. METHODS: Clinical, pathologic, and diagnostic imaging findings in two patients with Ewing sarcoma (ES) and one with peripheral neuroepithelioma (PN) are presented. RESULTS: Second malignant neoplasms located in the extremities or pelvis were seen 12-18 years after initial diagnosis of unilateral (two patients) or bilateral (one patient) retinoblastoma. The patients with unilateral retinoblastoma were treated by enucleation only; the other received ocular radiation therapy and chemotherapy. To the knowledge of the authors, this is the first documentation of round blue cell tumor after unilateral retinoblastoma. CONCLUSIONS: ES and PN should be included in the differential diagnosis of malignant neoplasms occurring after treatment of unilateral or bilateral retinoblastoma. PMID- 8467461 TI - Effect of surgery on peripheral blood lymphocyte locomotion through type I collagen. AB - BACKGROUND: Locomotion of peripheral blood lymphocytes (PBL) through peritumoral matrix is obligatory for tumor cell killing. The authors investigated the effect of surgery on lymphocyte locomotion and compared it with the effect on natural killer cell cytotoxicity (NKCC). METHODS: PBL from 12 patients with cancer were assessed for locomotion in Type I rat-tail collagen. Preoperative and postoperative locomotion (after 20 hours of incubation) and NKCC were estimated. RESULTS: Locomotion of lymphocytes through collagen increased significantly after operation in 6 of 12 patients, whereas only 1 of 12 had a decrease (P < 0.001). Short-term (20-hour incubation) exposure of the locomotory HSB cell line to patient plasma samples did not affect their migration. NKCC, as estimated against K562 target cells with the use of the 51Cr-release assay, decreased 5-50% after operation in 9 of 12 patients (P = 0.006). No correlation could be demonstrated between the changes in locomotion and NKCC (regression analyses), nor were identifiable clinical factors associated with these changes. CONCLUSIONS: Locomotion of PBL through collagen increases after operation in patients with cancer, whereas possibly independent factors may decrease postoperative NKCC. PMID- 8467464 TI - Determinants of home versus hospital terminal care for patients with gynecologic cancer. AB - BACKGROUND: This study reviewed all patients managed by the Gynecologic Oncology service of a tertiary care facility (n = 468) whose deaths occurred between 1980 and 1990 to ascertain the site of death and potential factors affecting whether patients died at home or in a hospital. METHODS: Gynecologic Oncology Tumor Registry data were analyzed for patient diagnosis, age at diagnosis, age at death, marital status, insurance coverage, and year of death in relation to location of death. RESULTS: This study found that 78% of patients died in the hospital, and 22% died at home. The mean terminal hospital stay was 15 days. The variables examined in this study could only accurately predict location of death in 59% of the cases. Examination of the variable year of death, however, demonstrated that the likelihood of death in the hospital generally increased from 1980 to 1990, despite introduction of diagnosis related groups and aggressive efforts by caregivers to facilitate and encourage death at home. CONCLUSIONS: Philosophical and economic considerations to the contrary, a significant majority of terminal patients with gynecologic cancers will die in a hospital, thus extensively utilizing our limited health resources. PMID- 8467463 TI - Intensive alternating drug pairs for treatment of high-risk childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study. AB - BACKGROUND: To prevent drug resistance, the authors designed a protocol that featured early intensive rotating drug pairs as part of the therapy for acute lymphoblastic leukemia (ALL). METHODS: After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were given in 30 weeks: A--intermediate-dose methotrexate (IDMTX) plus intermediate-dose mercaptopurine (MP); B--cytosine arabinoside (AC) plus daunorubicin (DNR); C--AC plus teniposide (VM-26). Triple intrathecal chemotherapy (AC, MTX, and hydrocortisone) was given for central nervous system (CNS) prophylaxis. Continuation therapy consisted of weekly MTX and daily MP until 2.5 years of continuous complete remission had been achieved. RESULTS: Seventy-four children (age range, 1-19 years) at high risk of relapse were treated. Of 55 with B-lineage (early pre-B, pre-B) ALL, 24 have failed (2 induction failures, 2 deaths from infection, and 20 relapses). The event-free survival (EFS) rate at 4 years was 55.5% (standard error [SE] +/- 7.7%). Of 19 patients with T-cell ALL, 12 have failed (2 induction failures and 10 relapses). The EFS rate at 4 years was 32.6% (SE +/- 26.8%). Toxicities were significantly more common after AC and DNR or AC and VM-26 than IDMTX and MP. There were no toxicity-related deaths during intensive treatments. CONCLUSION: Early intensive rotating therapy is tolerable and warrants consideration for additional trials of patients with high-risk, B-lineage ALL. PMID- 8467465 TI - Angiosarcoma of the breast after lumpectomy and radiation therapy for adenocarcinoma. PMID- 8467466 TI - Osteosarcoma in a 26-month-old girl. PMID- 8467467 TI - Colon cancer survival in Finland. PMID- 8467468 TI - Abnormalities of chromosome 22 in human brain tumors determined by combined cytogenetic and molecular genetic approaches. AB - Southern blot hybridization studies were performed on a panel of 130 blood/tumor samples from brain neoplasms including all major histologic subtypes: 50 meningiomas, 18 neurinomas, 56 gliomas, and six others. To detect abnormalities involving chromosome 22, polymorphic probes were used to analyze eight loci located in this chromosome: D22S9, IGLV, D22S20, D22S32, MB, PDGF-B, D22S80, and D22S171. Loss of heterozygosity (LOH) was observed in 40 cases including monosomy, terminal, and interstitial deletions, which suggest the location of recessive tumor genes in certain chromosome 22 subregions (22q11.3-q12 in neurinomas and meningiomas, and 22q13 in malignant gliomas). Cytogenetic studies were performed in parallel on the same tumors, in most instances corroborating the presence of abnormalities for chromosome 22. Nevertheless, discrepancies between the cytogenetic and molecular findings were observed in several cases, suggesting that the use of both methodologies in combination might provide key information on the incidence and extent of the abnormalities involving chromosome 22 in human brain tumors. PMID- 8467469 TI - Cytogenetic studies in three xenografted nasopharyngeal carcinomas. AB - Cytogenetics results of three xenografted nasopharyngeal carcinomas (NPC) are reported. One (C15) was almost diploid and had only an isochromosome 1q, trisomy 2, and loss of chromosome X. The two other tumors, C17 and C19, were hypodiploid and had complex karyotypes with some variations. Nonrandom structural abnormalities of chromosomes 1, 3, 8, and 17 were observed. A correlation between a del(17)(p11-12) observed in C17 and loss of both alleles of p53 recently shown in this tumor is emphasized. PMID- 8467470 TI - Chromosome 9 anomalies as the primary clonal alteration in a case of squamous cell carcinoma of the epiglottis. AB - We present the cytogenetic characterization of a short-term culture of a primary squamous cell carcinoma of the epiglottis from a 67-year-old male patient who was admitted to this hospital for treatment. This patient had a history of chronic exposure to tobacco and alcohol, environmental carcinogens known to be related to the etiology of the disease. The tumor karyotype showed three distinct clones: 1) cells with chromosome 9 anomalies; 2) cells with chromosome 9 and other clonal structural anomalies involving chromosomes 1, 11, 14, and 17; and 3) cells whose chromosomes were partially or totally pulverized. The anomalies on chromosome 9 were homozygous inversion (p12q13), deletions at regions q22, q34.1, and p13, and i(9q) formation. Structural clonal anomalies on other chromosomes included translocations, deletions, and isochromosome formation. The presence of a chromosome 9 anomaly alone or in conjunction with other anomalies suggests that this aberration may be a nonrandom primary event in the progression of squamous cell carcinoma of the head and neck. PMID- 8467471 TI - Involvement of 22q12 in a neurofibrosarcoma in neurofibromatosis type 1. AB - We describe the cytogenetic and molecular genetic findings in a neurofibrosarcoma arising in a patient affected by neurofibromatosis type 1. Multiple chromosomal rearrangements were found but only a few of them were identified as clonal abnormalities, including a deletion of chromosome 22, which at the molecular level proved to be interstitial, mainly involving the 22q12 region. Loss of heterozygosity for markers D22S32 and MB was observed. These findings are in agreement with previous data which suggest a possible involvement of a gene located at 22q11-q13.1 during the neoplastic development of some neurofibromatosis type 1-associated tumors. PMID- 8467472 TI - Cytogenetic analysis of six bronchial carcinoids. AB - Short-term cultures from four typical and two atypical primary bronchial carcinoids were cytogenetically analyzed. A lung metastasis from one of the atypical carcinoids was also analyzed. Of the four typical carcinoids, two had normal chromosome complements, while the other two had the karyotypes 46,X, -X, +7/47,XX, +7/47,XX, +X/46,XX and 47,XX, +7/46,XX. Both atypical carcinoids had chromosome abnormalities. One had the karyotype 45-46,X, X,del(1)(q32),add(17)(p13), +add(19)(p13), -22, +r/47,XX, +X. The second carcinoid had the karyotype 78-81,XXY, +Y, +1,t(2;8)(q21;q24), +3, +4, +del(4) (q25), +5, +6,der(6)t(6;6)(q21;p21)x2, +7, +7, -10,add(14)(p11-13), +19, -21, +1 4mar. The metastasis from this carcinoid had the same aberrations, except that the del(4)(q25) had been lost and one to two markers had been gained. PMID- 8467473 TI - Trisomy 14 in hematologic diseases. Another non-random abnormality within myeloid proliferative disorders. AB - Two cases of myelodysplastic syndrome (MDS) and a case of acute nonlymphoblastic leukemia (ANLL) with a trisomy 14 are presented. The series of results derived from our cases, and those previously reported, strongly suggest that this anomaly may be another nonrandom change, confined within myeloid disorders and associated with patients' advanced age, marked tendency to bone marrow dysplastic features, normal platelet values, and not unfavorable prognosis. PMID- 8467474 TI - Rhabdomyosarcoma. A cytogenetically interesting case report. AB - Chromosomal analysis was performed on the tumor tissue in a case of ocular rhabdomyosarcoma. Cytogenetic analysis revealed multiple clonal abnormalities. Derivative(5)t(1;5)(q21;q35) and t(2;11) (q21;q23) were present in all the metaphases analyzed (100%). Translocation(1;19)(q21;q13) was observed in 61% of the metaphases. Other clonal abnormalities present included +i(6p)(85%),i(17q)(38%),18q+(57%), 4p+ (38%), loss of the Y chromosome (33%), and presence of double minutes (12.8%). PMID- 8467475 TI - Cytogenetic analysis of posterior uveal melanoma. AB - Cytogenetic analysis was performed on short-term cultures of primary tumor samples from seven patients with posterior uveal melanoma. Informative data were obtained from four patients, all of whom had a near-diploid chromosomal number and clonal chromosomal alterations. Analysis of one patient's tumor revealed monosomy 3 as the only cytogenetically distinguishable aberration. Trisomies of chromosome 8 and i(8)(q10) were detected in two other patients in combination with monosomy of chromosome 3. The fourth patient's karyotype displayed two different translocations. One translocation, der(6)t(6;8)(q12;q13.1), resulted in the over-representation of 8q13.1-->qter and a partial monosomy of 6q12-->qter; the other translocation, der(9)t(6;9)(p12;p23), produced a partial trisomy of 6p12-->pter and a partial monosomy of 9p23-->pter. These results support the view that the recurring pattern of chromosomal rearrangements in ocular melanoma is unique from that associated with cutaneous malignant melanoma. Furthermore, these results help confirm that chromosomes 3, 6, and 8 are nonrandomly altered in ocular melanoma. PMID- 8467476 TI - Karyotypic analysis of CCRF-CEM and drug-resistant cell lines with stable and unstable ploidy. AB - Karyotypic studies were performed on methotrexate (MTX)- and vincristine (VCR) resistant cell lines derived from the human T-cell leukemia CCRF-CEM cell line. We noted karyotypic selection and additional chromosome change associated with acquisition of drug-resistance. Furthermore, we observed that both the parental and MTX-resistant sublines, CEM/MTX R1-3, had a tendency to ploidy change. Karyotypic studies of malignant cells have shown that polyploidy is frequently a consequence of a single sporadic event, followed by growth and selection of the polyploid clone [1]. In this study, however, various karyotypic clones were identified with near- and pseudotetraploid karyotypes that appeared to be derived from different near- and pseudodiploid sidelines. Polyploidy was invariably associated with loss of at least two of the four chromosomes 8 whether the pseudodiploid sideline from which it was derived carried one or both chromosomes 8. In contrast, neither polyploid clones nor loss of chromosome 8 was noted in the CEM/VCR R cells. PMID- 8467477 TI - Sister chromatid exchange in Waldenstrom's macroglobulinemia. AB - Results on sister chromatid exchange (SCE) frequency and interchromosomal distribution in bone marrow and peripheral blood cultures from patients with Waldenstrom's macroglobulinemia are reported. PHA-stimulated bone marrow cultures showed increased SCE frequencies in all 12 patients examined. The increase was particularly high in two cases (17.07 and 16.77 SCE/cell, respectively) and, in one of them, a very high SCE level was found in PHA-stimulated peripheral blood culture (40.81 SCE/cell). In LPS-stimulated cultures, increased SCE levels were observed in some patients. Comparison between SCE frequency in bone marrow cell cultures with either mitogen showed a significant increase in PHA-stimulated cultures. Analysis of the interchromosomal SCE distribution revealed significant differences with respect to the control values; however, these differences were variable in the different patients. In pooled data of PHA-stimulated bone marrow cultures, there were differences between expected and observed SCEs in chromosomes 1 and 2 and in B, E, F, and G chromosome groups. Results of cell cycle modifications are also reported. PMID- 8467478 TI - Acute lymphoblastic leukemia with trisomy 21 constitutional mosaicism. AB - Acute lymphoblastic leukemia was diagnosed in an 11-year-old girl with mild signs of Down's syndrome. She was known since birth to have a constitutional mosaicism (46,XX/47,XX,+21c). At initial diagnosis of acute leukemia, additional chromosome changes were found in bone marrow blasts: hyperdiploidy > 50, with a structural abnormality. She was treated with a standard chemotherapeutic protocol, and has remained in complete remission for more than 3 years. The constitutional mosaicism evolved toward normalization year after year in the blood and under the effect of chemotherapy in the bone marrow. PMID- 8467479 TI - FISH: a useful technique in the verification of clonality of random chromosome abnormalities. AB - Random chromosome abnormality is an important issue in clinical cytogenetics, especially in cancer cytogenetics. The significance of random abnormalities needs to be well defined. In the present study, ten patients with malignant hematologic disorders were analyzed by classical cytogenetic techniques and fluorescence in situ hybridization (FISH) procedures. Cytogenetic studies showed all ten patients to have a single cell with trisomy, i.e., +8, +8 (5 cases), +12, +15, +18, +20, and +21, respectively. FISH necessitated revision of the cytogenetic diagnosis and confirmed the clonality of these "random" abnormalities. PMID- 8467480 TI - Derivative (11)t(7;11)(q11;q24) in a child with acute megakaryoblastic leukemia. AB - We document the clinical, morphologic, and cytogenetic findings in a 2 1/2-year old patient with acute megakaryoblastic leukemia. Cytogenetic analysis of peripheral blood leukemic cells revealed the presence of a der(11)t(7;11)(q11;q24). Chromosome 7 involvement is observed in nearly half of all cases of megakaryoblastic leukemias, however, the type of abnormality differs widely from one case to another. The der(11)t(7;11)(q11;q24) described here is the first reported to our knowledge. PMID- 8467481 TI - A new pericentric inv(8) in acute nonlymphocytic leukemia. AB - Chromosome studies were carried out on unstimulated bone marrow cells from a patient with a diagnosis of acute nonlymphocytic leukemia (FAB M6 ANLL). Cytogenetic analysis revealed a mosaic chromosome pattern 46,XX/46,XX,inv(8)(p21q24). This pericentric inversion has not been previously described in ANLL. Because, fragile sites, zinc finger gene loci, and the MYC protooncogene have been localized to band 8q24, a putative role for these sites and genes could be considered. PMID- 8467482 TI - Interstitial deletion of 9q in a case of acute myeloid leukemia (FAB M6) PMID- 8467483 TI - Transcriptionally active chimeric gene derived from the fusion of the AML gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. PMID- 8467484 TI - Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: interaction of c-myc and transforming growth factor alpha in hepatic oncogenesis. AB - Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc complementary DNA and mouse metallothionein 1 promoter-human transforming growth factor alpha complementary DNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumorigenesis. Coexpression of c-myc and transforming growth factor alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumors were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. These observations suggest that the interaction of c-myc and transforming growth factor alpha, and possibly other combinations of nuclear oncogenes and growth factors, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. PMID- 8467485 TI - Immunohistochemical localization of parathyroid hormone-related protein in human prostate cancer. AB - Parathyroid hormone-related protein (PTHrP) is produced by a variety of malignant tumors and has been implicated as a major cause of humoral hypercalcemia of malignancy. Expression of PTHrP in prostate cancer tissue was studied immunohistochemically using 33 radical prostatectomy specimens from patients with clinically localized carcinoma of the prostate. None of these patients demonstrated hypercalcemia prior to the surgery. Acetone-methyl benzoate-xylene processed, paraffin-embedded tissues were stained with a validated mouse monoclonal antibody to an amino acid fragment, PTHrP(109-141), using the streptavidin-peroxidase enzyme conjugate method. All cases (33 of 33; 100%) studied demonstrated some degree of immunoreactivity throughout the cytoplasm of the tumor cells, but immunostaining was absent from inflammatory and stromal cells. The intensity of the staining appeared to directly correlate with increasing tumor grade. The widespread immunohistochemical localization of PTHrP in carcinoma of the prostate suggests that PTHrP may play some local role in the growth of transformed cells in the prostate. Furthermore, overexpression of PTHrP may be a possible marker to evaluate the malignant potential of carcinoma of the prostate. PMID- 8467486 TI - In vivo inhibition of insulin-like growth factor I gene expression by tamoxifen. AB - Tamoxifen, a partial antagonist to the estrogen receptor, is widely used in the treatment of breast cancer and is currently being evaluated as a breast cancer preventative agent in large-scale clinical trials. Recent clinical research has demonstrated that tamoxifen administration is associated with a reduction of serum insulin-like growth factor I (IGF-I) concentration. We demonstrate here that tamoxifen, when administered in an in vivo experimental system previously used to demonstrate its cytostatic effect on breast cancer cell proliferation, inhibits the expression of the IGF-I gene in common target organs for breast cancer metastasis. Furthermore, while our prior experimental studies have demonstrated an inhibitory effect of tamoxifen on growth hormone output, we show here for the first time that the suppression of IGF-I gene expression associated with tamoxifen administration is in part a consequence of a pituitary-independent action of the drug. Because IGF-I is a potent mitogen for breast cancer cells, this newly described activity of tamoxifen may contribute to its antineoplastic properties, particularly with regard to inhibition of metastasis seen both in animal models and clinically. PMID- 8467487 TI - Ribozyme-mediated modulation of human O6-methylguanine-DNA methyltransferase expression. AB - A synthetic oligonucleotide containing ribozyme sequences targeted to the 5' region of the human O6-methylguanine-DNA methyltransferase (MGMT) mRNA has been constructed. This ribozyme demonstrates cleavage activity in vitro in the presence of Mg2+. To determine whether this ribozyme can function in vivo, HeLa CCL2 cells were transfected with a mammalian expression vector containing the ribozyme sequence. Following selection and expansion of individual transfectants, a stable clone was isolated that lacks both MGMT mRNA and protein. Molecular analysis of this cell line indicates that in vivo cleavage of MGMT mRNA is responsible for the lack of MGMT activity. PMID- 8467488 TI - Activation of the Abelson tyrosine kinase activity is associated with suppression of apoptosis in hemopoietic cells. AB - A chromosomal translocation uniquely associated with chronic myeloid leukemia leads to the formation of a chimeric gene, bcr-abl, on the Philadelphia chromosome. The BRC-ABL protein displays an uncontrolled tyrosine kinase activity similar to that seen with the transforming oncogene of the Abelson murine leukemia (ABL) virus (v-abl). An interleukin 3 dependent cell line, IC.DP, has been transfected with a gene encoding a temperature sensitive v-ABL. In the absence of interleukin 3 at the restrictive temperature for ABL tyrosine kinase activity IC.DP cells died via apoptosis. At the permissive temperature ABL tyrosine kinase activity promoted IC.DP cell survival but not proliferation. ABL therefore can specifically suppress apoptosis. PMID- 8467489 TI - A structural role for metal ions in the "wild-type" conformation of the tumor suppressor protein p53. AB - In human tumors, many different point mutations of the p53 gene knock out suppressor function and induce the p53 polypeptide to adopt an immunologically distinct, "mutant" conformation. Here we show that exposure to the metal chelator 1,10-phenanthroline induces wild-type p53 to adopt the mutant conformation and that this process is reversible. Conversion to mutant phenotype also occurs after exposure to (a) an organic mercurial reagent targeting cysteinyl residues and (b) low concentrations of mercury or cadmium. We propose that binding of metal ions, most probably zinc, to conserved cysteinyl residues stabilizes the tertiary structure of wild-type p53. PMID- 8467490 TI - Prevention of orthotopic human lung cancer growth by intratracheal instillation of a retroviral antisense K-ras construct. AB - An orthotopic human lung cancer model in nu/nu mice was used to study the effect of an antisense K-ras (AS-K-ras) retroviral construct on tumor growth in vivo. A 2-kilobase genomic AS-K-ras DNA fragment linked to a beta-actin promoter was cloned into the LNSX retroviral vector. The recombinant construct was packaged into GP+envAm12 cells and titers greater than 10(6) colony-forming units/ml were obtained. Irradiated (350 cGy) nu/nu mice were first inoculated intratracheally with 10(5) H460a human large cell lung carcinoma cells which have a codon 61 mutation of the K-ras oncogene. Three days later they received intratracheal instillation of viral supernatant (5 x 10(6) colony-forming units/ml) from either LNSX, LNSX-AS-K-ras, LNSX-sense-K-ras producer cells, or medium daily for 3 days. At autopsy, 30 days after tumor cell inoculation, 90% of the control mice had tumors whereas 87% of mice treated with the LNSX-AS-K-ras viral supernatant were free of tumors. The efficacy of the viral supernatant was dose dependent. Intratracheal administration of retroviral LNSX-AS-K-ras supernatant prevents the growth of human lung cancer cells implanted orthotopically in nu/nu mice. PMID- 8467491 TI - Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. AB - Human cells can become multidrug resistant (MDR) by an increase in the activity of the MDR1 P-glycoprotein or by other, as yet unknown mechanisms, referred to as non-P-glycoprotein mediated MDR (non-Pgp MDR). S. P. C. Cole et al. [Science (Washington DC), 258: 1650-1654, 1992] recently reported that in two cell lines non-Pgp MDR was associated with the overexpression of a new putative membrane transporter gene, MRP. Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW 1573 (non-small cell lung cancer) and GLC4 (small cell lung cancer). In all of ten SW-1573 derived lines examined the MRP mRNA level was equal to that in the parental line, whereas MRP was 25-fold overexpressed in a resistant subline of GLC4. We conclude that overexpression of MRP cannot account for all forms of non Pgp MDR. PMID- 8467492 TI - Identification of a putative tumor marker in breast and colon cancer. AB - Application of a recently developed phospholipid saponification procedure to malignant colon or breast tissue produces an unidentified phosphodiester resonance in the 31P nuclear magnetic resonance spectrum which appears to correlate with malignancy. Glycerol phosphodiesters were prepared from a malignant breast tumor by a Folch extraction of the tissue followed by saponification of the resulting phospholipids. These compounds were separated by ion exchange chromatography and the compound responsible for this new resonance was isolated and identified as glycerol 2-phosphoglycerol by high resolution nuclear magnetic resonance spectroscopy. Confirmation of this structure was achieved by chemical synthesis of glycerol 2-phosphoglycerol. Attempts to isolate the phospholipid responsible for this resonance showed that it is not derived from a new class of phospholipids but is most likely an artifact of the new saponification procedure used. Glycerol 2-phosphoglycerol is formed via glycerol 2,3-(cyclic) phosphate derived from phosphatidylcholine followed by reaction with glycerol. Malignant tissue is more prone to produce this compound than is nonmalignant tissue and the differences between these tissue types may be a form of phosphatidylcholine that is present in higher concentrations in malignant tumor membranes than in those of normal tissue. PMID- 8467493 TI - Entry of protein toxins in polarized epithelial cells. AB - The action of a number of toxins used in the formation of immunotoxins was studied in polarized cells. Diphtheria toxin inhibited protein synthesis most efficiently when added to the basolateral side of the kidney cells, MDCK-I, MDBK and Pt K2, and the colon carcinoma cell Caco-2. Similar findings were made with Pseudomonas aeruginosa exotoxin A in MDCK-I, Pt K2, and Caco-2 cells, and with modeccin and volkensin in MDCK-I cells. In accordance with the toxicity data, diphtheria toxin bound specifically to the basolateral side of MDCK-I cells but not to the apical side. On the other hand, in the trophoblastic BeWo cell line there was little or no difference in the toxic effect of P. aeruginosa exotoxin A and modeccin added to the two sides. The plant toxins ricin and abrin and the bacterial Shigella toxin inhibited protein synthesis approximately equally well in all cell lines tested whether they were added apically or basolaterally. The results indicate that protein toxins are able to enter cells from both the apical and basolateral sides provided receptors are present. The consequences for the preparation of immunotoxins are discussed. PMID- 8467494 TI - Chromatophoromas and chromatophore hyperplasia in Pacific rockfish (Sebastes spp.). AB - Pacific rockfish from Cordell Bank, off central California (United States), were collected and histologically examined from 1985 to 1990. Hyperplastic and neoplastic cutaneous lesions, involving dermal chromatophores, were observed in five species; yellowtail rockfish (Sebastes flavidus), bocaccio (S. paucispinis), olive rockfish (S. serranoides), widow rockfish (S. entomelas), and chilipepper rockfish (S. goodei). Yearly prevalences were highest in S. paucispinis (29-38%). Prevalence was initially low in S. flavidus, but increased more than 3-fold from 1985 (7.5%) to 1990 (25%). The majority of lesions were black, but white, yellow, orange, red, and mixed-color variants were also seen. Lesions were found in skin, fins, lips, gingiva, tongue, urogenital papilla, conjunctiva, and cornea of the eye. Flat lesions were consistent with melanophore (black), xanthophore (yellow or orange), and erythrophore (red) hyperplasia. Neoplastic lesions included melanophoromas, amelanotic melanophoromas, xanthophoromas, erythrophoromas, and mixed chromatophoromas. Although etiology has not been determined, interest is currently focused on potential exposure to chemical and radioactive carcinogens from the Farallon Island Radioactive Waste Dump, 30 km to the south. PMID- 8467495 TI - Loss of differentiation control in transformed 3T3 T proadipocytes. AB - Nontransformed 3T3 T mesenchymal/proadipocyte stem cells can be readily induced to differentiate, yet previous work has shown that 3T3 T cells that are spontaneously or virally transformed not only lose their normal growth control mechanisms but also lose the ability to differentiate. Loss of growth control can be due to autocrine mechanisms in some transformed cells, but the mechanisms involved in disrupting differentiation control are poorly understood. Our goal is to further define the growth and differentiation defects that arise in neoplastically transformed cells and the mechanisms underlying those defects. For example, exogenous transforming growth factor beta and tumor necrosis factor, both of which are secreted aberrantly by some tumor cells, are known inhibitors of different steps of the normal 3T3 T adipocyte differentiation process, suggesting a potential role as autocrine factors in disrupting differentiation of transformed 3T3 T cells. In the current study we transformed 3T3 T cells in vitro with chemical or UV irradiation treatment in order to determine if the acquisition of the transformed phenotype after these treatments is also associated with loss of differentiation control as it is with spontaneously or virally transformed cells. Four chemically and two UV-treated 3T3 T cell lines were isolated from type III foci and all have been found to be tumorigenic in syngeneic animals and to have lost the ability to differentiate. Relative to the parental cell line the differentiation abilities of the transformed clones ranged from 0 to less than 5%. In this regard, we also analyzed the normal and aberrant expression of three growth factors and differentiation inhibitors in transformed cells. Both transforming growth factor alpha and beta were found to be expressed in non-transformed 3T3 T cells as determined by Northern blot analyses. In addition, both were found to be down-regulated during differentiation of 3T3 T cells. Transformed/differentiation-defective 3T3 T cells expressed varied levels of transforming growth factor alpha and beta. Three of the new transformed clones expressed particularly high levels of transforming growth factor alpha. Very low levels of tumor necrosis factor expression were found in the normal cells and the transformed cells appeared to express tumor necrosis factor at similar levels. In contrast, none of the transformed cells expressed any of the differentiation specific genes tested (lipoprotein lipase, glycerol-3-phosphate dehydrogenase, etc.). Even a transformed clone which could undergo growth arrest but not morphological differentiation expressed no differentiation-specific genes. Together, these data suggest that neoplastic transformation in general disrupts differentiation control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8467496 TI - Accumulation of p53 protein in human esophageal precancerous lesions: a possible early biomarker for carcinogenesis. AB - The level of p53 protein was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, dysplasia, carcinoma in situ, and carcinoma) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linxian and Huixian in the Henan province). Tissue sections were incubated with p53 antibodies for immunostaining. Conventional hematoxylin and eosin stain was also used. In surgically resected esophageal specimens, elevated p53 protein levels were found in the cell nuclei in tissues with precancerous and cancerous lesions. From basal cell hyperplasia to dysplasia to carcinoma in situ, the p53 immunostain-positive cells increased in number, and their distribution had roughly the same pattern as that of the proliferating cells. However, positive stain was not observed in the dividing basal cells of the normal epithelium of the surgically resected tissues. A similar pattern of immunostaining was observed in the abnormal tissues of the biopsy samples from the symptom-free subjects. An intriguing observation is that some p53 immunostain-positive cells were observed in 3 of 6 cases of histologically normal epithelia of biopsy samples. Only the papillary immunostaining pattern was observed in these three "normal" cases. Although the molecular basis for such positive stain remains to be investigated, it is possible that p53 protein accumulation occurs early in the pathogenesis of esophageal cancer and that p53 mutation is closely associated with the initiation of this cancer. The accumulation of p53 protein may be a promising early biomarker for identifying high-risk subjects for esophageal cancer. PMID- 8467497 TI - Clinical value of determination of urokinase-type plasminogen activator antigen in plasma for detection of colorectal cancer: comparison with circulating tumor associated antigens CA 19-9 and carcinoembryonic antigen. AB - We determined urokinase-type plasminogen activator antigen (u-PA), gastrointestinal cancer-associated antigen (CA 19-9), and carcinoembryonic antigen (CEA) in the plasma of patients with colorectal cancer at the time of clinical tumor detection and in a group of patients with Crohn's disease and analyzed the specificity of these tumor markers. u-PA, CA 19-9, and CEA were indicative for colorectal cancer in 75.5%, 51.5%, and 51.5% of tumor patients, respectively, with a specificity of 79.3%, 94%, and 97.5%. Sensitivity increased when two or all three markers were determined in identical blood samples, whereby a combination of u-PA and CEA exhibited the highest sensitivity value (90.9%) as compared to the combinations of u-PA and CA 19-9 or CA 19-9 and CEA. The use of all 3 markers did not lead to further increased sensitivity. False negative results were obtained in 3 of 32 cancer patients (9.1%, using one of 3 markers as indicative for malignant disease). These results indicate the benefit of multiparametric tumor marker analyses including u-PA antigen for the diagnosis of colorectal cancer. PMID- 8467498 TI - Phase I and pharmacological study of the pulmonary cytotoxin 4-ipomeanol on a single dose schedule in lung cancer patients: hepatotoxicity is dose limiting in humans. AB - 4-Ipomeanol (IPO), a naturally occurring pulmonary toxin, is the first cytotoxic agent to undergo clinical development based on a biochemical-biological rationale as an antineoplastic agent targeted specifically against lung cancer. This rationale is based on preclinical observations that metabolic activation and intracellular binding of IPO, as well as cytotoxicity, occurred selectively in tissues and cancers derived from tissues that are rich in specific P450 mixed function oxidase enzymes. Although tissues capable of activating IPO to cytotoxic intermediates in vitro include liver, lung, and kidney, IPO has been demonstrated in rodents and dogs to undergo in situ activation, bind covalently, and induce cytotoxicity preferentially in lung tissue at doses not similarly affecting liver or kidneys. Although the drug was devoid of antitumor activity in the conventional murine preclinical screening models, cytotoxic activity was observed in human lung cancers in vitro and in human lung cancer xenografts in vivo, adding to the rationale for clinical development. Somewhat unexpectantly, hepatocellular toxicity was the dose-limiting principal toxicity of IPO administered as a 30-min infusion every 3 weeks to patients with lung cancer. In this study, 55 patients received 254 courses at doses almost spanning 3 orders of magnitude, 6.5 to 1612 mg/m2. Transient and isolated elevations in hepatocellular enzymes, predominantly alanine aminotransferase, occurred in the majority of courses of IPO at 1032 mg/m2, which is the recommended IPO dose for subsequent phase II trials. At higher doses, hepatocellular toxicity was more severe and was often associated with right upper quadrant pain and severe malaise. Toxic effects were also noted in other tissues capable of activating IPO, including possible nephrotoxicity in a patient treated with one course of IPO at 154 mg/m2 and severe, reversible pulmonary toxicity in another patient who received nine courses of IPO at doses ranging from 202 to 826 mg/m2. Although individual plasma drug disposition curves were well described by a two-compartment first order elimination model, The relationship between IPO dose and area under the disposition curve was curvilinear, suggesting saturable elimination kinetics. At the maximum tolerated dose, the mean half-lives (lambda 1 and lambda 2) were 6.7 and 114.5 min, respectively. Renal excretion of parent compound accounted for less than 2% of the administered dose of IPO. An unidentified metabolite was detected in the plasma of patients treated at higher doses. No objective antitumor responses were observed; however, stable disease persisted for at least eight courses in 27% of patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8467499 TI - Glucocorticoids coordinately disrupt a transforming growth factor alpha autocrine loop and suppress the growth of 13762NF-derived Con8 rat mammary adenocarcinoma cells. AB - We have demonstrated previously that the synthetic glucocorticoid dexamethasone suppresses the growth of Con8 rat mammary tumor cells, which are derived from the 13762NF transplantable, hormone-responsive rat mammary adenocarcinoma. Dexamethasone inhibited [3H]thymidine incorporation into Con8 cells at high cell density under both serum and serum-free conditions. Fractionation in nonreducing sodium dodecyl sulfate-polyacrylamide gels of proteins secreted from dexamethasone-treated and untreated Con8 mammary tumor cells revealed two size classes of glucocorticoid inhibited mitogenic activities; a larger M(r) 27,000 33,000 and a smaller M(r) 5,000-12,000 activity. Both size classes of mitogens restimulated the growth of glucocorticoid-suppressed Con8 cells suggesting that they can act in an autocrine fashion. The smaller mitogen was identified as transforming growth factor alpha (TGF-alpha) since this activity competed with 125I-epidermal growth factor (EGF) for EGF receptor binding and was selectively immunodepleted with monoclonal TGF-alpha antibodies but not with EGF antibodies. Western blots and radioreceptor assay of Con8-secreted proteins revealed that glucocorticoids inhibited the production of a M(r) 5500 immunoreactive TGF-alpha protein by 10-fold. Consistent with a steroid effect on the level of TGF-alpha production, rather than on its activity, the specific mitogenic activities of the TGF-alpha s secreted by dexamethasone-treated and untreated Con8 cells were identical to that of recombinant human TGF-alpha. Treatment of intact cells with suramin, which dissociates ligand-receptor complexes, revealed that the EGF receptor-mediated mitogenic response is functional in both glucocorticoid-treated and untreated cells. Taken together, our results demonstrate that glucocorticoids suppress Con8 mammary tumor cell growth and disrupt a potential TGF-alpha autocrine loop which results in a dramatic reduction in the level of extracellular TGF-alpha. PMID- 8467500 TI - Overexpression of transforming growth factor alpha overrides the glucocorticoid mediated suppression of Con8 mammary tumor cell growth in vitro and in vivo. AB - In a preceding paper (D. B. Alexander et al., Cancer Res., 53: 1808-1815, 1993), we demonstrated that the in vitro glucocorticoid inhibition of Con8 mammary tumor cell growth is accompanied by the disruption of a transforming growth factor alpha (TGF-alpha) autocrine loop. This growth suppression response functions in vivo since proliferation of Con8-derived tumors was inhibited in rats treated with the synthetic glucocorticoid, dexamethasone. The effect of dexamethasone on Con8-derived tumor growth was reversible in that tumors rapidly grew at the site of inoculation after discontinuing injections of dexamethasone. To test the in vivo relationship between the glucocorticoid growth suppression response and the TGF-alpha autocrine loop, Con8 cells were transfected with a TGF-alpha expression vector and single cell-derived neomycin-resistant subclones were recovered. [3H]Thymidine incorporation of cultured monolayers of transfected Con8 mammary cells and measurement of tumor diameters in rats revealed that dexamethasone failed to suppress the in vitro proliferation or in vivo tumor growth of Con8 derived cells producing high constitutive levels of secreted TGF-alpha. In contrast, both the in vivo and in vitro growth of Con8 cells transfected with vector controls were fully suppressible by glucocorticoids. Consistent with our in vitro observations, these results demonstrate that the regulation of TGF-alpha production plays a key role in the in vivo glucocorticoid suppression of Con8 derived mammary tumor growth. PMID- 8467501 TI - Ovarian cancers express and process progastrin. AB - Gastrin synthesis in ovarian tumors has been described in a few isolated cases associated with the Zollinger-Ellison syndrome. Consequently, ovarian gastrin synthesis has been considered exceptional. In order to evaluate whether expression of gastrin in ovarian tumors indeed is rare, we examined the expression and processing of progastrin in 16 malignant and 5 benign ovarian tumors and 4 normal postmenopausal ovaria. Using a library of sequence specific radioimmunoassays, cleavage by processing-like enzymes, and gel chromatography, we found that one-half of the malignant tumors expressed significant concentrations of amidated gastrins [6.7 +/- 2.7 (SEM) pmol/g; range, 1.4-20.0 pmol/g, n = 7]. The concentrations of glycine-extended gastrins and progastrins were low (0.25 +/- 0.03 and 1.4 +/- 0.4 pmol/g, respectively) but higher than in controls and benign tumors. Chromatography showed that the majority of the bioactive gastrins was unsulfated gastrin-17. The other half of the malignant tumors expressed glycine-extended gastrins and progastrins (0.2 +/- 0.03 and 0.6 +/- 0.1 pmol/g; n = 9), but the amidation of the peptides was impaired (0.1 +/- 0.03 pmol/g). Low concentrations of glycine-extended gastrins and progastrins were detected in the normal ovarian tissues (0.2 +/- 0.05 pmol/g tissue and 0.2 +/- 0.06 pmol/g, respectively, n = 4) and in the benign tumors (0.1 +/- 0.02 pmol/g and 0.5 +/- 0.03 pmol/g; n = 5). Amidated gastrins were undetectable, except in low amounts in a single benign tumor (0.2 pmol/g tissue). The results show that postmenopausal ovaria and neoplastic ovarian tissues express the gastrin gene at peptide level. The synthesis and processing of progastrin increase considerably in malignant tumors. PMID- 8467502 TI - Modulation of both cisplatin nephrotoxicity and drug resistance in murine bladder tumor by controlling metallothionein synthesis. AB - The role of metallothionein (MT) in cisplatin (cis-DDP) resistance and renal toxicity was investigated in C3H mice inoculated with mouse bladder tumor (MBT 2). C3H mice were inoculated s.c. with 1 x 10(6) MBT-2 cells/mouse on day 0. Mice were given injections of proparglyglycine (PPG) (500 mumol/kg s.c.) once a day for 3 days from day 7 to day 9 and with ZnSO4 (200 mumol/kg s.c.) once a day for 2 days from day 8 to day 9. cis-DDP (50 mumol/kg i.p.) was administered 10 days after MBT-2 cell inoculation. Since MT contents in the tumor and kidneys were significantly increased by administration of ZnSO4, both the antitumor activity of cis-DDP and its renal toxicity were reduced. However, coadministration of PPG reduced MT induction in tumor without affecting the level of renal MT. As a result, PPG could clearly overcome the MT-mediated cis-DDP resistance of tumors without compromising the protective effect exerted by renal MT on nephrotoxicity of the drug. It was suggested, therefore, that PPG may be a promising adjunct in cancer chemotherapy to overcome the drug resistance of tumors caused by the elevated level of MT. PMID- 8467503 TI - Protection of bone marrow stromal cells from the toxic effects of cyclophosphamide in vivo and of ASTA-Z 7557 and etoposide in vitro by ammonium trichloro(dioxyethylene-O-O')tellurate (AS101). AB - The immunomodulator AS101 has previously been shown to protect mice from lethal and sublethal doses of cyclophosphamide (CYP). AS101 was also shown to protect BM granulocyte-macrophage colony-forming cells from the toxic effects of ASTA-Z 7557. In the present study we examined the ability of AS101 to protect functional properties of BM stromal cells from the toxic effects of CYP in vivo or ASTA-Z in vitro. The functional properties of stromal cells from CYP-injected mice were tested with respect to stromal cell number and viability as reflected by the number of colony-forming unit fibroblasts, the ability of established stromal layers to secrete colony-stimulating factor and interleukin 6, as well as the capacity to support hemopoietic cells. All of these parameters were tested from day 1 to day 7 after CYP treatment. We demonstrate that all stromal functions are severely damaged following CYP treatment. Pretreatment of mice with 10 micrograms AS101 24 h before injection of 250 mg/kg CYP resulted in a significant amelioration of stromal cell functions as early as 24 h following CYP treatment. In addition we show that prior incubation of BM cells with AS101 protects the development of stromal colony-forming unit fibroblasts from the toxic effects of ASTA-Z, a potent derivative of CYP, and etoposide, a derivative of podophyllotoxin. These results strongly suggest the usefulness of AS101 in counteracting chemotherapy-induced BM microenvironmental suppression and the important role of the compound as an adjunct treatment of cancer when used in combination with CYP. The data also suggest the effectiveness of AS101 in purging bone marrow when used concomitantly with ASTA-Z or etoposide. PMID- 8467504 TI - Apoptosis induced by anthracycline antibiotics in P388 parent and multidrug resistant cells. AB - The effect of the topoisomerase II inhibitor doxorubicin and its non-cross resistant analogue annamycin on DNA degradation and programmed cell death was examined in murine leukemia P388 cells. P388 parental cells exposed to various concentrations of doxorubicin and annamycin for 24 h displayed dose-dependent DNA cleavage: at 1 microM, both doxorubicin and annamycin were effective in inducing DNA breakdown, but at 10 microM, the effect was markedly decreased or totally absent. In multidrug-resistant P388/Dox cells, doxorubicin did not cause DNA cleavage, while 10 microM annamycin had a significant effect. By agarose gel analysis, drug-induced DNA fragmentation showed the characteristic pattern of internucleosomal ladder. Morphologically, P388 cells treated with 1 microM doxorubicin or annamycin for 24 h showed a reduction in cell volume and condensation of nuclear structures. Similar changes were observed in P388/Dox cells exposed to 10 microM annamycin for 24 h but not in cells exposed to 10 microM doxorubicin. Time course studies demonstrated that DNA fragmentation was detected 12 h after incubation with 1 microM doxorubicin or annamycin, while loss of membrane integrity appeared at 24 h, thus indicating that DNA degradation was a preceding event. DNA fragmentation caused by doxorubicin and annamycin was inhibited by the RNA synthesis inhibitor actinomycin D, the protein synthesis inhibitor cycloheximide, and the endonuclease inhibitor aurintricarboxylic acid. Drug-induced cell death was partially prevented by cycloheximide and aurintricarboxylic acid, thus suggesting that the apoptotic process caused by these drugs requires gene expression, synthesis of new proteins, and activation of endogenous nucleases. In contrast, DNA cleavage was not affected by incubating cells with 1 mM ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid, thus indicating that intracellular calcium depletion does not affect anthracycline-induced apoptosis. The results obtained demonstrate that the cell killing effect of anthracyclines is mediated, at least in part, by the induction of apoptosis. PMID- 8467505 TI - Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. AB - Bcl-2 is a novel protooncogene which prolongs cell survival and suppresses apoptosis. We examined whether constitutive expression of transfected human bcl-2 conferred resistance to two different DNA damaging drugs, nitrogen mustard (HN2) and camptothecin (CPT) in a murine, IL-3 dependent cell line (FL5.12). HN2 treatment produced 2-fold less cell death and DNA degradation in cells overexpressing bcl-2 relative to control cells transfected with a construct bearing only the neoR gene. DNA degradation was characterized by oligonucleosomal length fragments indicating that programmed cell death or apoptosis had occurred. Equimolar HN2 produced similar extents of interstrand cross-link formation and repair in each cell line. Cell cycle characteristics were similar for both cell lines following equimolar HN2 treatment, exhibiting a brief S phase delay followed by a longer G2 arrest. Time course studies indicated that DNA fragmentation occurred following peak G2 arrest in control cells and 12 h later in bcl-2 transfected cells. Equimolar CPT exposure also induced 2-fold less death and apoptotic DNA fragmentation in bcl-2 transfected compared to control cells. DNA single strand break formation and resealing kinetics were comparable in both cell lines following equimolar CPT treatment. CPT caused similar cell cycle perturbations in both cell lines, with a brief S phase block detectable 12 h after an equimolar drug dose. Kinetic studies showed apoptosis occurred following maximal S phase arrest in control and 12 h later in bcl-2 transfected cells. By contrast, IL-3 withdrawal produced rapid and extensive DNA degradation and apoptosis in controls 24 h postwithdrawal, and this process was inhibited 3-4 fold in bcl-2 transfectants. Cell cycle analysis showed both cell lines arrested in G0/G1 following IL-3 removal. In summary, bcl-2 transfection affords a 2-fold protection from HN2 and CPT cytotoxicity and decreases drug induced apoptosis in FL5.12 cells, despite the different mechanisms of action and cell cycle effects of each agent. Bcl-2 overexpression appears to represent a novel drug resistance mechanism of potential clinical significance. PMID- 8467506 TI - Inhibition of protein tyrosine phosphatase by the antitumor agent gallium nitrate. AB - Protein tyrosine phosphatases (PTPases) play an important role in regulating cell growth and transformation. We report that the antitumor agent gallium nitrate is a potent inhibitor (concentration producing 50% inhibition, 2-6 microM) of detergent-solubilized cellular membrane PTPase from Jurkat human T-cell leukemia cells and HT-29 human colon cancer cells. This is the first report of a selective, small molecule drug inhibitor of PTPase. Gallium nitrate did not inhibit CD45, a PTPase found in the membranes of hemopoietic lineage cells such as Jurkat cells. Studies with gallium nitrate and a series of gallium-containing analogues revealed no correlation between growth-inhibitory activity in Jurkat and HT-29 cells and the ability to inhibit detergent-solubilized PTPase. Gallium nitrate and most of the gallium analogues penetrate poorly into cells. In contrast, a gallium-hydrogen peroxide complex inhibits DNA synthesis in Jurkat cells and induces the accumulation of phosphotyrosines on multiple intracellular proteins in this cell line. Gallium-hydrogen peroxide complex and gallium nitrate have similar inhibitory activity toward detergent-soluble PTPase. This is a new mechanism of action for gallium nitrate but it is not known if the inhibition of PTPase is related to the antitumor activity of gallium nitrate. PMID- 8467507 TI - Yeast cells can enter a quiescent state through G1, S, G2, or M phase of the cell cycle. AB - We have examined the ability of the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae to enter a quiescent state through G1, S, G2, or M phase of the cell cycle. We monitored entry to a quiescent state by measuring two well known properties of quiescent cells, i.e., long-term viability and a dramatic increase in resistance to thermal heat shock relative to cycling cells. For this purpose, we made use of yeast cell division cycle (cdc) mutants with which we could arrest most of the cells in culture at specific points in the cell cycle. We find that these eukaryotes can enter a reversible quiescent state at any of the points in the cell cycle we examined if the cells are exposed to starvation conditions (starvation normally signals cells to leave the cell cycle). These findings indicate that mechanisms involved in entry to and exit from a quiescent state can operate not only in G1 phase (leading to G0 arrested cells) but can also operate in S, G2, and M phases of the cell cycle. These findings may be important for clinical oncology in cases where tumor cells escape the cytotoxic effects of chemotherapeutic agents. It may be that escape from the effect of these drugs is due to tumor cells entering quiescent states at points in the cell cycle other than G1 phase. Perhaps different chemotherapeutic strategies may be required to kill tumor cells reentering the cell cycle from other than G1. PMID- 8467508 TI - Human myelomonocytic cell line THP-1 produces a novel growth-promoting factor with a wide target cell spectrum. AB - Conditioned medium from a human myelomonocytic cell line THP-1 promoted the growth of a wide variety of cell types, i.e., human and mouse myeloid cells (HL 60, U937, K562, and M1), mouse T-cells (EL-4), human B cells (Daudi and Raji), mouse mastocytoma cells (IC-2), human melanoma cells (A375-C6), mouse transformed fibroblast cells (L929), human lung fibroblast cells (TIG-1), and mouse bone marrow fibroblast/stromal-like cells. The growth-promoting activity was acid labile. The activity was resistant to 50 degrees C for 5 min but completely lost in 5 min at 70 degrees C. The activity was resistant to treatment with trypsin but sensitive to chymotrypsin alpha, Pronase E, and proteinase K, indicating the proteinous nature of this activity. The activity was lost by dithiothreitol and 2 mercaptoethanol. Molecular weight (M(r) 50,000-70,000) was estimated by gel filtration-high performance liquid chromatography. After the sequential anion exchange, hydrophobic, and hydroxylapatite high performance liquid chromatography, the partially purified factor exhibited the same target cell spectrum as the conditioned medium. PMID- 8467509 TI - An anticancer drug-sensitive murine erythroleukemia clone: implications for the mechanism of action of antineoplastic drugs. AB - The mechanism(s) by which anticancer drugs kill tumor cells remains obscure. The studies reported here were undertaken with the view that the mechanism may be understood in part through an analysis of anticancer drug-sensitive clones. We have isolated a murine (Friend) erythroleukemia clone in which drug sensitivity was correlated with increased differentiation, suggesting that anticancer drug induced cell death may be based on differentiation or a differentiation-dependent mechanism. In addition, this clone showed a high propensity for constitutive differentiation and frequent appearance of large multinucleate cells. Morphologically similar large aberrant cells were observed after the treatment of parental (745A) cells with Adriamycin (or bleomycin). We attribute these morphological defects occurring in clone 3-1 or in the parental cell line after anticancer drug treatment to a defective or inhibited cell cycle function. We suggest that the putative cell cycle defect in clone 3-1 is coupled to the increased drug-induced differentiation and resulting cell death. From a broader perspective, the studies reported here suggest that the search for and design of new anticancer drugs be directed at agents that modulate differentiation functions. PMID- 8467510 TI - Altered messenger RNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas. AB - Seventy-nine esophageal carcinoma patients were studied for genetic abnormalities in the p53 and Rb tumor suppressor genes. Single-strand conformation polymorphism analysis and DNA sequencing were used to detect p53 point mutations, Northern blotting was used to examine abnormal expression of p53 and Rb, and polymerase chain reaction and Southern blotting were used to analyze allelic loss. Twenty five cases were analyzed by DNA sequencing to detect mutations in p53. Fourteen samples contained mutations within exons 5 through 9 of p53; seven had missense mutations giving rise to single amino acid substitutions. The remaining seven (50%) contained nonsense mutations leading to premature termination, five due to single base pair substitutions, and two that were the result of frameshift mutations. In other human tumors, p53 mutations are predominantly missense mutations, but our data as well as those from other groups show that nonsense mutations are common in human esophageal cancer. All but one of the constitutionally heterozygous samples containing mutations also manifested loss of the normal p53 allele; the one exception without allelic loss contained a silent mutation, which should not have had any affect on the p53 protein product. In addition, Northern blotting analysis revealed abnormalities (altered transcript size or mRNA levels) in 5 of 7 cases involving p53 and in 2 of 7 cases analyzed for Rb. Thirty-four cases were informative for allelic loss studies of both p53 and Rb; of these, 25 (74%) lost heterozygosity of p53, Rb, or both. When point mutations and mRNA expression abnormalities were also considered, 33 of 45 (73%) tumors informative for allelic loss assays of both genes as well as for mRNA or point mutation studies showed one or more abnormalities in p53 or Rb. Our results strongly suggest that a unique profile of molecular alterations involving p53 and Rb characterizes human esophageal cancer and that these specific genetic lesions are important in the development and/or progression of most human esophageal carcinomas. PMID- 8467511 TI - Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis. AB - Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia, and in the hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa. PMID- 8467512 TI - Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma. AB - Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis. PMID- 8467513 TI - Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays. AB - DNA strand breaks which occur in HL-60 cells as a result of activation of endonuclease during apoptosis induced by cell treatment with the DNA topoisomerase I inhibitor camptothecin and topoisomerase II inhibitors teniposide, 4'-(9-acridinylamino)-3-methanesulfon-m-anisidide, and fostriecin were labeled in situ, in individual fixed and permeabilized cells, with biotinylated dUTP (detected by fluoresceinated avidin), using the terminal deoxynucleotidyl transferase or nick translation assays. During the early stage of apoptosis, prior to nuclear fragmentation, the breaks were predominantly localized at the nuclear periphery, close to the nuclear envelope. In more advanced stages, all cellular DNA, then localized within the cell as dense, homogeneous granules of a variety of sizes, was strongly labeled, indicating extensive and more uniform distribution of breaks throughout genomic DNA. Bivariate analysis of the incorporated biotinylated dUTP and cellular DNA content by flow cytometry made it possible to estimate the kinetics of the labeling reaction and relate DNA breaks to cell position in the cycle. The kinetics of biotinylated dUTP incorporation was faster, and the distinction of cells with DNA breaks was more pronounced, using the terminal transferase rather than the nick translation assay. Camptothecin, teniposide, and 4'-(9-acridinylamino)-3 methanesulfon-m-anisidide induced DNA breaks preferentially in S-phase cells, having little effect on cells in the G1 phase of the cycle. In contrast, fostriecin affected cells indiscriminately, in all phases of the cell cycle. The method of detection of DNA strand breaks (3'-hydroxyl termini) in individual cells offers several advantages and can be applied to clinical material (tumor biopsies) to study the induction of apoptosis in tumors during treatment, as a possible prognostic marker. The protein-associated DNA breaks in the "cleavable" DNA-topoisomerase complexes, which are the primary lesions induced by the inhibitors and precede apoptosis, were not detectable by the present methods. PMID- 8467514 TI - Radiation-enhanced expression of major histocompatibility complex class I antigen H-2Db in B16 melanoma cells. AB - Exposure of eukaryotic cells to ionizing radiation induces several cellular responses including DNA repair, arrest of DNA synthesis, and increased synthesis of specific cellular proteins. We derived from the murine melanoma cell line B16 F10 a clonal isolate (M1) that was exposed to a total dose of 5000 cGy in 25 fractions, according to a protocol that reflects the standard for current radiotherapeutic regimens. We measured, by flow cytometry of fluorescence-stained cells, the surface expression of the two major histocompatibility complex class I antigens H-2Db and H-2Kb in irradiated M1 cells and untreated M1 controls. We found that after 2000 cGy, expression of H-2Db antigen was enhanced in irradiated cells versus controls. Radiation-induced expression of H-2Db antigen appeared to be selective, since no up-regulation of the H-2Kb antigen was detectable, and persisted for at least 5 weeks following the last irradiation. Enhanced H-2Db antigen expression correlated with increased steady-state levels of H-2Db mRNA in irradiated cells. These results are consistent with the notion that enhanced expression of major histocompatibility complex class I antigens is part of a long lasting stress response elicited in cells by radiation. PMID- 8467515 TI - Differential diagnosis of oral mucosal ulcerations. PMID- 8467516 TI - The immediate chairside splint. PMID- 8467517 TI - A multidisciplinary approach for localized juvenile periodontitis: a case report. PMID- 8467518 TI - Acupuncture anesthesia/analgesia for pain and anxiety control in dental practice. Part I: Theory and application. PMID- 8467519 TI - The fascinating story of maxillofacial prosthetics. PMID- 8467520 TI - Oral amalgam tattoos: a diagnostic study. PMID- 8467521 TI - Indirect resin restoration-a proper technique to ensure success. PMID- 8467522 TI - Multiple hamartoma syndrome (Cowden's disease): a case report. PMID- 8467523 TI - Divergent neural beta tubulin from the Antarctic fish Notothenia coriiceps neglecta: potential sequence contributions to cold adaptation of microtubule assembly. AB - The cytoplasmic microtubules of the cold-adapted Antarctic fishes, unlike those of homeotherms and temperate poikilotherms, assemble and function at body temperatures in the range -1.8 to +2 degrees C. To determine whether alterations to the primary sequence of beta tubulin may contribute to enhancement of microtubule assembly at cold temperatures, we have cloned and sequenced a 1.8 kilobase neural beta-chain cDNA, Ncn beta 1, from an Antarctic rockcod, Notothenia coriiceps neglecta. Based on nucleotide sequence homology, Ncn beta 1 probably corresponds to a class-II beta-tubulin gene. The 446-residue beta chain encoded by Ncn beta 1 is closely related (sequence homology approximately 95%) both to the neural class-I/II isotypes and to the neural/testicular class-IV variants of higher vertebrates, but the sequence of its carboxy-terminal isotype defining region (residues 431-446) has diverged markedly (> or = 25% change relative to the I/II/IV referents). Furthermore, the Ncn beta 1 polypeptide contains six unique amino-acid substitutions (five conservative, one nonconservative) not found in other vertebrate brain isotypes, and the carboxy terminal region possesses a unique tyrosine inserted at position 442. We conclude that Ncn beta 1 encodes a class-II beta tubulin that contains sequence modifications, located largely in its interdimer contact domain, that may contribute to cold adaptation of microtubule assembly. PMID- 8467524 TI - Microtubule-associated motility in cytoplasmic extracts of sea urchin eggs. AB - We have developed a method for producing sea urchin egg cytoplasmic extracts which support substantial microtubule-associated motility, particularly minus end directed motility characteristic of cytoplasmic dynein. Particles translocated along microtubules and axonemes predominantly in the minus end direction; microtubules and axonemes glided across the coverslip surface only in the plus end direction (as expected for a minus-end directed motor bound to the coverslip surface); and microtubules crosslinked into bundles in an antiparallel orientation. Velocities of particle and microtubule translocation were in the range of 0.5-1.8 microns/sec. Vanadate at 10 microM inhibited all gliding of the microtubules and axonemes, yet bidirectional particle transport persisted. Vanadate at concentrations of 25 microM and higher inhibited nearly all microtubule-based motility in the preparation and produced parallel bundling of the microtubules. Motility was slowed but not stopped in the presence of 5 mM AMP PNP. Usually when a particle bound to a microtubule wall, it moved to the microtubule minus end. These particles often remained attached to the minus end. When a microtubule plus end in the shortening phase of dynamic instability reached a stationary particle on the microtubule, sometimes normal minus end directed motility was activated, or at other times the particle remained attached to the shortening plus end. PMID- 8467525 TI - Myosin-I in mammalian liver. AB - Myosin-I refers to a class of proteins with a molecular weight of approximately 110-kDa, which have characteristics of conventional myosin but are unable to form filaments. Previous studies have implicated myosin-I in motile cellular processes including cell migration and phagocytosis. Although the first example of myosin-I in higher eukaryotes was the intestinal 110K-calmodulin complex, which forms in microvilli the lateral links connecting the core bundle of actin filaments to the membrane, myosin-I has now been shown to be a component of rat kidney and to be present in bovine adrenal gland and brain. We have now purified and characterized two polypeptides from rat liver which have several characteristics of the intestinal 110K-calmodulin complex. Both liver polypeptides are solubilized with ATP and co-elute on gel filtration with calmodulin. The polypeptides, of 110-kDa and 130-kDa, bind calmodulin in 1 mM EGTA. Both polypeptides bind to F-actin in an ATP reversible fashion, and crosslink actin filaments. The purified polypeptides possess an actin-activated Mg(2+)-ATPase activity typical of brush border myosin-I. A polyclonal antiserum directed against the chicken intestinal 110-kDa polypeptide recognizes both rat liver polypeptides, whereas another serum recognizes the 130-kDa but not the 110-kDa rat liver polypeptide. Controlled proteolysis of the purified polypeptides with alpha-chymotrypsin indicates that the two polypeptides are distinct but related. Immunofluorescence microscopy on isolated hepatocytes shows distribution of myosin-I to be vesicular, distributed throughout the cytoplasm, but more concentrated near the nucleus. These data contribute new evidence by several functional criteria that multiple myosin-I molecules are present in higher organisms and may coexist in a single cell type. PMID- 8467526 TI - Molecular neurobiology of olfaction. AB - Odor discrimination is mediated via dendritic cilia of olfactory receptor neurons. Odorants traverse the aqueous mucous interphase that lines the surface of the olfactory neuroepithelium and interact with odorant receptors, which are members of the superfamily of G-protein-linked receptors. These interactions trigger synthesis of second messengers, including cyclic AMP and inositol triphosphate. Cyclic AMP opens a cation channel to elicit the generator current, which depolarizes the cell and, ultimately, leads to action potentials. Inositol triphosphate opens a calcium channel in the ciliary plasma membrane. Calcium entering through both this channel and the cyclic nucleotide-gated channel modulates the response to odorants by amplifying the generation of cyclic AMP after binding to calmodulin. Calcium also is essential for desensitization of olfactory receptor neurons. Differential expression of odorant receptors of diverse ligand specificities by different olfactory neurons ensures that the structures and concentrations of odorants that reach the chemosensory surface are encoded as distinct patterns of neuronal activity, which are relayed to the brain where they take shape as characteristic odor sensations. PMID- 8467527 TI - The growth and signalling defects of the ggs1 (fdp1/byp1) deletion mutant on glucose are suppressed by a deletion of the gene encoding hexokinase PII. AB - Yeast cells defective in the GGS1 (FDP1/BYP1) gene are unable to adapt to fermentative metabolism. When glucose is added to derepressed ggs1 cells, growth is arrested due to an overloading of glycolysis with sugar phosphates which eventually leads to a depletion of phosphate in the cytosol. Ggs1 mutants lack all glucose-induced regulatory effects investigated so far. We reduced hexokinase activity in ggs1 strains by deleting the gene HXK2 encoding hexokinase PII. The double mutant ggs1 delta, hxk2 delta grew on glucose. This is in agreement with the idea that an inability of the ggs1 mutants to regulate the initiation of glycolysis causes the growth deficiency. However, the ggs1 delta, hxk2 delta double mutant still displayed a high level of glucose-6-phosphate as well as the rapid appearance of free intracellular glucose. This is consistent with our previous model suggesting an involvement of GGS1 in transport-associated sugar phosphorylation. Glucose induction of pyruvate decarboxylase, glucose-induced cAMP-signalling, glucose-induced inactivation of fructose-1,6-bisphosphatase, and glucose-induced activation of the potassium transport system, all deficient in ggs1 mutants, were restored by the deletion of HXK2. However, both the ggs1 delta and the ggs1 delta, hk2 delta mutant lack detectable trehalose and trehalose-6 phosphate synthase activity. Trehalose is undetectable even in ggs1 delta strains with strongly reduced activity of protein kinase A which normally causes a very high trehalose content. These data fit with the recent cloning of GGS1 as a subunit of the trehalose-6-phosphate synthase/phosphatase complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467528 TI - Recombination initiated by double-strand breaks. AB - The HO endonuclease was used to introduce a site-specific double-strand break (DSB) in an interval designed to monitor mitotic recombination. The interval included the trp1 and his3 genes inserted into chromosome III of S. cerevisiae between the CRY1 and MAT loci. Mitotic recombination was monitored in a diploid carrying heteroalleles of trp1 and his3. The normal recognition sites for the HO endonuclease were mutated at the MAT alleles and a synthetic recognition site for HO endonuclease was placed between trp1 and his3 on one of the chromosomes. HO induced cleavage resulted in efficient recombination in this interval. Most of the data can be explained by double-strand gap repair in which the cut chromosome acts as the recipient. However, analysis of some of the recombinants indicates that regions of heteroduplex were generated flanking the site of the cut, and that some recombinants were the result of the cut chromosome acting as the genetic donor. PMID- 8467529 TI - Interaction between mitochondrial DNA and mitochondrial plasmids in Claviceps purpurea: analysis of plasmid-homologous sequences upstream of the lrRNA-gene. AB - Homology of two linear, mitochondrial (mt) Claviceps purpurea plasmids, pClK1 and pClT5, to the upstream region of the large ribosomal RNA gene in the mtDNA of three strains (W3, T5 and K) has been investigated in detail to explore the widespread phenomenon of homology between mt plasmids and mtDNA in C. purpurea. Sequence comparison indicates that recombination between free plasmids and mtDNA is the cause of the observed homology. The process is similar to the integration of the structurally related adenoviruses into the mammalian genome. As in other fungi, palindromic sequences seem to be involved in this mitochondrial recombination process. PMID- 8467530 TI - Isolation, sequencing, and characterization of crp-5, a gene encoding a Neurospora ribosomal protein. AB - A Neurospora crassa cytoplasmic ribosomal protein gene, crp-5, has been isolated and characterized. The cDNA was isolated by a differential screening of a cDNA library for glucose-inducible genes. The cDNA was subsequently used to identify and isolate crp-5 genomic sequences. Computer analysis of the DNA sequences showed that they contain an open reading frame which encodes a protein homologous to the rat ribosomal protein S26. The crp-5 mRNA levels are regulated in a carbon source-dependent manner. The organization of the gene and the region upstream of the coding sequences are discussed. PMID- 8467531 TI - Transfer of genetic information from the mycoparasite Parasitella parasitica to its host Absidia glauca. AB - The infection of the model organism Absidia glauca by P. parasitica is accompanied by the fusion of both mycelia. By two lines of evidence we were able to show that this process is associated with the transfer of genes. First, auxotrophically labelled A. glauca mutants are efficiently complemented as a consequence of transfer of the parasite's genetic material. Second, for a plasmid coded dominant marker (neomycin resistance), which is expressed in either organism, we proved the presence of plasmid DNA in recombinant recipients by molecular analysis at the DNA level. We propose the term para-recombinants for describing recombinant inter-generic chimaerae, which are generated as a consequence of mycoparasitism. PMID- 8467532 TI - Messenger RNA intron in the nuclear 18s ribosomal RNA gene of deuteromycetes. AB - Introns within messenger RNA genes have characteristic border sequences and a conserved region near the 3' end of the intron. All are involved in splicing to produce the mature mRNA. Introns in ribosomal RNA genes have less well-defined borders and contain no internal conservation. We report here mRNA-type introns located near the 3' end of the 18s rRNA genes of the deuteromycetes Phialophora americana and Cenococcum geophilum. Inserted sequences of various sizes have also been located at the same point in several other deuteromycete species. PMID- 8467533 TI - Gibberella pulicaris transformants: state of transforming DNA during asexual and sexual growth. AB - A genetically fertile, trichothecene-producing plant pathogen, Gibberella pulicaris (Fusarium sambucinum), was transformed with three different vectors: cosHyg1, pUCH1, and pDH25. All three vectors carry hph (encoding hygromycin B phosphotransferase) as the selectable marker. Transformation frequency was 0.03 transformants per mumg of DNA for pDH25 and 0.5 for pUCH1 or cosHyg1. The vector DNA sequences integrated at different sites into the fungal genome. Transformants were classified into three types based upon distinctive integration patterns: type A contained a single, intact copy of the vector at one site per genome; type B contained multiple tandem copies or a combination of single and multiple tandem copies at one or more sites per genome; type C contained a partial vector copy at one site per genome. While the transformants with cosHyg1 and pUCH1 were type A or B, type C was unique to pDH25 transformants. Type A and C transformants were both meiotically and mitotically stable. However, type B multiple inserts were unstable in mitosis and meiosis since: (1) multiple tandem copies were deleted; (2) rearrangements occurred during premeiosis; and (3) inserts in one of the type B transformants became methylated during premeiosis. Differential expression of transforming sequences between spore germination and mycelial growth was also observed among type B transformants. The ability to transform G. pulicaris with the resulting varied features of integration patterns and the behavior of transforming DNA during mitosis and meiosis provides a means to isolate, manipulate, and study cloned genes in this mycotoxin-producing plant pathogen. PMID- 8467534 TI - Isolation and transformation of uracil auxotrophs of the lignin-degrading basidiomycete Phanerochaete chrysosporium. AB - Uracil auxotrophs of Phanerochaete chrysosporium were isolated using 5 fluoroorotate resistance as a selection scheme. The ura3 auxotrophs deficient in orotidylate decarboxylase and ura5 auxotrophs deficient in orotate phosphoribosyl transferase were characterized by enzyme assays and complementation tests. The ura5 auxotrophs were transformed to prototrophy with the ura5 gene from the ascomycete Podospora anserina. The ura3 auxotrophs were transformed to prototrophy with the ura3 gene from the basidiomycete Schizophyllum commune. The P. chrysosporium ura3 gene was isolated from a lambda EMBL3 genomic library using the S. commune ura3 gene as a probe. A 6.6-kb fragment incorporating the ura3 gene was subcloned into Bluescript SK+(pURA3.1) and used to transform P. chrysosporium ura3 auxotrophic strains. The pURA3.1 insert was mapped for restriction sites and the approximate location of the ura3 gene within the insert was determined. Double auxotrophic strains were transformed with either of two marker genes and the resulting single auxotrophic strains were crossed to demonstrate genetic recombination between two nuclei of identical genetic background. PMID- 8467535 TI - Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum. AB - The inheritance of an extrachromosomal 6-kb element has been examined in the human malaria parasite Plasmodium falciparum. A single base pair difference in the cytochrome b gene from the 6-kb element of two different cloned lines of the parasite was identified, and used as a marker in a cross in the mosquito stage of the life cycle. Analysis of 59 individual hybrid oocysts resulting from this cross clearly demonstrated that inheritance of the cytochrome b gene was uniparental. This observation makes it possible to investigate the inheritance and evolution of cytoplasmic traits, including certain forms of drug resistance, in natural populations of this parasite. PMID- 8467536 TI - A region of heterogeneity adjacent to the 5s ribosomal RNA gene of cereal rusts. PMID- 8467537 TI - Genomic organization of a cellulase gene family in Phanerochaete chrysosporium. PMID- 8467538 TI - Tracheal intubation and laryngoscope design. PMID- 8467539 TI - Perioperative cardiovascular complications associated with blunt thoracic trauma. AB - The purpose of this study was to examine the frequency and importance of intraoperative mortality, arrhythmias and hypotension in the presence of thoracic trauma and to determine the effect of myocardial contusion on these perioperative complications. Over a two-year period patients with evidence of blunt thoracic injury who required surgery within 24 hr of admission were studied. The anaesthetist filled in a questionnaire on intraoperative events. Patients were also studied for the presence of myocardial injury with radionuclide angiography (RNA), at autopsy or at thoracotomy. Two hundred and one patients were studied. The intraoperative and overall mortality was 7.9% and 22.9% respectively. Of the operating room survivors the incidence of intraoperative arrhythmias and hypotension was 3.8% and 26.5% respectively. Only 5.9% of patients had a suspected or confirmed myocardial contusion. Patients were divided into two groups, those without myocardial injury were designated Group I, while those with myocardial contusion were designated Group II. The Group II patients had a greater severity of injury and intraoperative mortality (54.4%) than those in Group I (4.6%) P < 0.05. Intraoperative deaths were attributed to, with one exception, non-cardiac causes. There were no differences in the incidences of arrhythmias and hypotension between patients with-or without myocardial injury surviving the operating room. All patients with blunt thoracic injury may develop intraoperative arrhythmias or hypotension. PMID- 8467540 TI - Intubating conditions and haemodynamic changes following thiopentone or propofol for early tracheal intubation. AB - Intubating conditions and haemodynamic changes were studied 30 sec after a fixed induction dose of thiopentone or propofol in patients scheduled for elective surgery. The hypnotic agent was preceded by the administration of papaveretum 10 mg three minutes before induction and alcuronium 0.2 mg.kg-1 at induction. Ease of intubation was graded and the study conducted in a randomised double-blind fashion. In the thiopentone group (n = 30) intubation was very easy in 73% compared with 79% in the propofol group (n = 29). In two patients in the propofol group the tracheas were moderately difficult to intubate but there were no failed intubations in either group. No patients recalled the intubation period on subsequent postoperative questioning. The immediate post-induction average systolic pressure in the thiopentone group decreased by 0.7% (range 15.9% increase to 25.3% decrease) whilst the post-intubation systolic pressure increased by 6.3% (range - 31.5% increase to 24.2% decrease). In the propofol group there was a decrease in systolic pressure after induction (average 14.4%; range 15.5% increase to 41.4% decrease, P < 0.05) but the subsequent pressor response to intubation was markedly attenuated compared with baseline (average systolic pressure decreased 15.5% (range 22.4% increase to 42.7% decrease)). Following intubation and maintenance, ventilation with nitrous oxide 70% and halothane 1% the systolic pressure decreased markedly in both groups with a greater reduction in the propofol group (P < 0.05). Compared with baseline there were increases (P < 0.0001) in heart rate in both groups from induction of anaesthesia to the end of study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467541 TI - Ventilatory requirements during laparoscopic cholecystectomy. AB - The purpose of this clinical study was to determine: (1) the increase in minute ventilation required to maintain preinsufflation arterial carbon dioxide tension (PaCO2) during laparoscopic cholecystectomy, and (2) whether end-tidal PCO2 (PETCO2) can be used as an index of PaCO2 and, therefore, of the adequacy of minute ventilation during the pneumoperitoneum. We measured PaCO2, PETCO2, expired minute volume (Vexp) standardized for body surface area (SA), airway and intra-abdominal pressure (P(aw), Pabd) during general anaesthesia for laparoscopic cholecystectomy just before and 30 min after the creation of a CO2 pneumoperitoneum in 28 healthy (ASA class 1 and 2) consenting adults. They were in the reverse Trendlenburg position (20 degrees) with a 5 degrees lateral tilt. Expired minute volume was increased from 3.75 (SEM +/- 0.12) to 4.19 (0.15) L.min 1 x m-2 to maintain PaCO2 close to control levels: 38.9 (0.8) vs 40.1 (0.6) mmHg 5.19 (0.1) vs 5.35 (0.08) kPa). In most of the patients (23/28), PETCO2 was less than 41 mmHg with a correlation between PaCO2 and PETCO2. In ten of these patients, (Pa-PET)CO2 was greater than the normal range. In 5/28, (Pa-PET)CO2 was negative. The "driving pressure" (P(aw)-Pabd) increased from 8.7 (1.0) to 10.4 (1.1) cm H2O, without any correlation between the increase in P(aw)-Pabd and that in Vexp. The results indicate the need for extra ventilatory requirement during laparoscopy and that PETCO2 is an imperfect index of PaCO2 under these circumstances. PMID- 8467542 TI - Patient-controlled epidural analgesia in labour: varying bolus dose and lockout interval. AB - This double-blind prospective study was designed to determine the best dose variables for patient-controlled epidural analgesia (PCEA) and to compare bolus only PCEA with continuous infusion epidural analgesia (CIEA) during the first stage of labour. Five groups of parturients self-administered 0.125% bupivacaine with 1:400,000 epinephrine and fentanyl 2.5 micrograms.ml-1 using PCA pumps programmed as follows: Group A, 2 ml bolus/10 min lockout interval (LI); Group B, 3 ml bolus/15 min LI; Group C, 4 ml bolus/20 min LI; Group D, 6 ml bolus/30 min LI; Group E, 8 ml.hr-1 continuous infusion. Hourly assessments included: VAS scores for pain and satisfaction, sensory and motor block, bupivacaine and fentanyl consumption. Blood samples were collected at birth for maternal and fetal fentanyl concentrations. Data from 68 patients showed no differences among groups in pain relief or maternal satisfaction. Most patients received excellent analgesia and those requiring extra epidural supplements were evenly distributed across groups. There was higher consumption of bupivacaine and fentanyl in Group E than in any of the other four groups: bupivacaine mg.hr-1, mean (SD), 9.4 (2.7) in Group E vs 5.2 (1.7) in Groups A-D inclusive (P < 0.0001); fentanyl microgram.hr-1, 19.6 (4.6) in group E vs 12.6 (7.5) in Groups A-D inclusive (P < 0.05). Motor block was minimal, whereas sensory levels were higher at the 3- and 4-hour assessments in Groups D and E than in all other groups (P < 0.05). Plasma fentanyl concentrations were < 0.5 ng.ml-1 in all samples and no sequelae from fentanyl were observed, apart from mild pruritus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467543 TI - Gastric pH and volume after oral fluids in the postpartum patient. AB - The aim of this study was to investigate the relationship between preoperative oral fluids and gastric pH and volume in women undergoing sterilization between one and five days postpartum. Fifty postpartum patients received 150 ml water approximately two to three hours before surgery while 50 postpartum and 50 non pregnant women were fasted from midnight. After induction of anaesthesia, gastric contents were aspirated using a Salem sump tube and the gastric pH and volume were measured. There were no differences in intragastric pH and volume, median (range), among the postpartum fasted group, 1.19 (0.74-4.57), 22 (1-78) ml, postpartum water group 1.18 (0.70-6.4), 25.5 (3-66) ml and the non-pregnant group 1.27 (0.51-6.63), 25 (3-69) ml. There was no correlation between postpartum interval, 60 (12-120) hr, and intragastric pH or volume. It is concluded that oral water may be given safely two to three hours preoperatively to patients more than one day postpartum. Intragastric volume and acidity were not increased and the findings in postpartum patients were similar to those found in non-pregnant patients. PMID- 8467544 TI - Blood transfusion in total hip arthroplasty: guidelines to eliminate overtransfusion. AB - This study was designed to evaluate the effect of transfusion guidelines on perioperative blood usage with a view to identifying a protocol for transfusion therapy in our hospital. Eighty consecutive patients with normal haemoglobin concentrations presenting for total hip arthroplasty were studied. The maximum allowable blood loss (MABL) was calculated for each patient using the formula of Kallos et al. Blood loss up to this value was replaced with Haemaccel. When the MABL was reached, a haematocrit (Hct) was performed and blood was given if the Hct was less than 30 in men and 27 in women. Otherwise replacement was with Haemaccel. All postoperative complications, duration of hospital stay, and physiotherapy compliance assessments were recorded. A discharge Hct > 36% was the criterion for overtransfusion. The results were compared with findings from a retrospective group before the introduction of these guidelines. Analysis of the data demonstrated a reduction in the frequency of transfusion (97% vs 32% P < 0.05), the volume transfused (2.7 vs 1.3 units P < 0.05), and the incidence of overtransfusion (45% vs 5% P < 0.05) between the two groups of patients. There was no difference between the groups in complication rate, duration of hospital stay or physiotherapy scoring. We conclude that the introduction of guidelines for transfusion in total hip arthroplasty patients has produced a marked reduction in blood usage in our hospital without detrimental effect. PMID- 8467546 TI - Delayed ischaemia of the hand necessitating amputation after radial artery cannulation. AB - We present a case of ischaemic hand injury in a patient, who had 95% occlusion of both the ulnar and radial arteries, after atraumatic placement of a left radial artery catheter. The presence of cigarette burns on the dorsum of the hand was highly suggestive of vascular compromise. There were no signs of vascular compromise after placement of the arterial line which was removed 24 hr later. Ten days after placement the patient complained of pain with ensuing ischaemic changes resulting in necrosis of the finger tips and eventual amputation of the hand. We recommend using other sites of arterial access such as axillary or superficial temporal artery in patients with severe peripheral vascular disease. PMID- 8467547 TI - Modification of intravenous lidocaine-induced convulsions by epinephrine in rats. AB - We studied intravenous lidocaine-induced convulsions in rats to determine whether added epinephrine influences the provocation of lidocaine toxicity. Wistar rats (200-250 g) were divided into three groups of ten, depending on the concentration of epinephrine added to lidocaine. Group 1: plain 1.5% lidocaine; Group 2: 1.5% lidocaine with 1:200,000 epinephrine; Group 3: 1.5% lidocaine with 1:100,000 epinephrine. After surgical preparation and recovery from anaesthesia, all rats received a continuous i.v. infusion of lidocaine (15 mg.ml-1) at a rate of 4.0 mg.kg-1 x min-1 until generalized convulsions occurred. The epinephrine-treated animals developed acute hypertension after one minute of lidocaine infusion (105 +/- 2 to 141 +/- 2 mmHg in Group 2 and 103 +/- 2 to 151 +/- 2 mmHg in Group 3). The PaO2 values in the epinephrine groups at the onset of convulsions were decreased significantly (88.3 +/- 1.0 to 84.0 +/- 1.5 mmHg in Group 2 P < 0.05 and 86.9 +/- 1.2 to 78.1 +/- 2.4 mmHg in Group 3 P < 0.01). However, these values were still within physiological ranges. Serum potassium concentrations in all groups were decreased P < 0.05, (4.24 +/- 0.09 to 3.52 +/- 0.12 mEq.L-1 in Group 1, 4.02 +/- 0.09 to 3.63 +/- 0.17 mEq.L-1 in Group 2, and 4.15 +/- 0.10 to 3.69 +/- 0.17 mEq.L-1 in Group 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467548 TI - Comparison of the direct effects of sevoflurane, isoflurane and halothane on isolated canine coronary arteries. AB - We have demonstrated previously, using dog epicardial arteries of different sizes, that isoflurane, like adenosine, is preferentially a small coronary artery dilator, whereas halothane, like nitroglycerin, is a large artery dilator. The present study was designed to compare the direct effects of sevoflurane with those of isoflurane and halothane. Proximal large coronary arteries with an outer diameter (o.d.) of 2.5-3.2 mm and distal small arteries of 0.6-0.9 mm o.d. were isolated from dogs and then cut into vascular rings. They were precontracted with KCl (20 mM), and their relaxant responses to anaesthetics were compared relative to the maximal responses induced by papaverine. Sevoflurane, halothane and isoflurane (1-3 human MAC) induced dose-dependent relaxation of these arteries. The relaxant response to sevoflurane did not differ between large and small arteries. However, the relaxant response of the large arteries to halothane (1.5 2.3%) was greater than that of small arteries (P < 0.01) and the response of small arteries to isoflurane (3.5%) was greater than that of large arteries (P < 0.05). In large arteries, the potency of the relaxant effect at equivalent human MAC could be ranked as halothane > or = sevoflurane > isoflurane, and, in small epicardial arteries as isoflurane > sevoflurane >> halothane. We conclude that, unlike isoflurane, sevoflurane is not a preferential dilator of small coronary arteries. PMID- 8467545 TI - Potassium and anaesthesia. AB - Potassium is the principle intracellular ion, and its concentration and gradients greatly influence the electrical activity of excitable membranes. Because anaesthesia is so intimately involved with electrically active cells, potassium concentrations in surgical patients have received considerable attention in diagnostic and therapeutic applications. With the ongoing evolution in the indications for potassium, it is important to review the role of potassium in cellular activity, in storage and regulation, in diseases that alter potassium homeostasis, and in the therapeutic implications of perioperative alterations of potassium concentration. A rational approach to abnormal potassium values and the use of potassium in the operating room is sought, based on a physiological understanding of risks and benefits. PMID- 8467549 TI - An analysis of laryngoscope blade shape and design: new criteria for laryngoscope evaluation. AB - Laryngoscope blade design has tended to be relatively arbitrary and so far scientific analysis has not allowed useful comparisons between blade shapes. A new theoretical method of analysing laryngoscope blades is introduced and uses the depth of insertion profiles of two angular measurements. One represents eyeline displacement and the other the forward space that the blade occupies at the level of the mandible. Photographs of straight and curved blades were studied on Cartesian graphs with the tip T, at the origin and handle fittings parallel to the x-axis of the graph. Then, IT is any line from the origin to the incisor surface and represents a point of contact with the upper incisors for a given depth of blade insertion. Angle EIT (eyeline displacement) is to a tangent from I along the lower lingual surface of the blade. Point M is on the upper lingual surface of the blade, at right angles to IT, 1/3 of the distance from I along IT. Angle MIT (forward space) may be positive or negative depending on whether M is in front of or behind IT. The angles EIT, MIT and their additive combination are used in blade analysis. Negative MIT compensates for eyeline displacement as Macintosh size 3 and 4 blades have better combination scores than Miller size 3. All three are superior to the straight Soper size 3 blade. The Macintosh size 1 and 2 blades are quite different from the larger Macintosh blades. This theoretical basis for blade analysis is consistent with commonly expressed clinical opinions and may influence blade design in the future. PMID- 8467550 TI - Computerized photo-plethysmography of the finger. AB - A microcomputer system for studying photo-plethysmography of the finger (PPF) was designed and applied to 50 non-premedicated healthy boys (one to ten years old) undergoing general anaesthesia (halothane in 70% N2O, with mechanical ventilation) for outpatient inguinal hernia repair. The purpose of this study was to assess the accuracy of computerized estimations of the photo-plethysmographic (arterial waves) amplitude and to evaluate whether or not PPF allows discrimination between two different surgical stimuli (skin incision, and manipulation of the spermatic cord). When anaesthesia was stable for at least five minutes (end-tidal halothane = 1.25-1.5%; PETCO2 = 32-38 mmHg; SpO2 > or = 98%; rectal temperature = 36.3-37 degrees C; ambient operating room temperature = 20-21 degrees C), and immediately before the skin incision, computerized estimations of the photo-plethysmographic (arterial waves) amplitudes (PPA) were recorded and saved for later comparison with direct (manual) measurements of the plethysmographic tracing, using an arbitrary scale of 0-255 units. Also, the values of PPA, systolic blood pressure, and pulse rate recorded immediately before the skin incision were later compared with the maximum changes in these same values recorded 30-90 sec after skin incision, and 30-90 sec after manipulation (traction+dissection) of the spermatic cord. Six boys (three to ten years old) stayed quiet enough, during induction of anaesthesia by mask, to allow regression analysis of PPA, systolic blood pressure, and pulse rate (Y) on end tidal halothane/70% N2O (X). Computerized estimations tended to give a higher reading, by between 0.2 to 0.8 units, than direct measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467551 TI - Difficult laryngoscopy made easy with a "BURP". AB - Displacement of the larynx by backward, upward and rightward pressure on the thyroid cartilage or "BURP" may improve visualization of the glottis in some cases of difficult direct laryngoscopy. In a patient with the Treacher-Collins syndrome in whom conventional laryngoscopy had proved impossible and tracheal intubation extremely difficult, this manoeuvre exposed the entire glottis and made tracheal intubation under direct vision easy. In a patient with protruding upper incisors and a prominent premaxilla which precluded a view of the glottis by conventional laryngoscopy, "BURP" again revealed the glottic opening and simplified the placement of an endotracheal tube. This experience suggests that "BURP" be considered as a potential aid in the management of difficult direct laryngoscopy. PMID- 8467552 TI - Plasma sufentanil concentration after intranasal administration to paediatric outpatients. PMID- 8467553 TI - Management of failed oral fibreoptic intubation with laryngeal mask airway insertion under topical anaesthesia. PMID- 8467554 TI - Patient recruitment for clinical research. PMID- 8467555 TI - Rheumatoid arthritis: how well do the theories fit the evidence? AB - In this brief review, inspired partly by a symposium at the autumn meeting of the British Society for Immunology, 1992, varying hypotheses concerning the etiopathogenesis of rheumatoid arthritis (RA) are explored and tested against current evidence. Immunogenetic considerations, whilst of interest, have not aided our understanding of the development of this disease. The association with restricted HLA-DR beta chain hypervariable sequences does not hold true with all cases of RA (but may be related to disease severity) and studies of T cell receptor (TCR) beta chain usage fail to show consistent oligoclonality of infiltrating T cells in the synovial compartment. Etiologies based on triggering by bacteria are also considered: homologies between the 'shared epitope' sequences of HLA-DR1 and DR4 beta chains, Escherichia coli dnaJ and Proteus haemolysin do not indicate any feasible mechanisms for the development of RA, and cannot explain the many cases in which such DR sequences do not occur, though new data from man and animals enhance interest in the role of bowel flora. Finally, the striking parallels between slow bacterial infections and RA, in terms of immunogenetics, pathology, IgG glycosylation abnormalities and autoimmune manifestations, are put forward as circumstantial evidence that such bacterial infections may underly, or trigger, this serious disease. PMID- 8467556 TI - Increased expression of interferon-gamma in hyperplastic lymph nodes from HIV infected patients. AB - Polyclonal B cell activation is characteristic of HIV infection and occurs in the presence of severe CD4+ lymphocyte depletion. In contrast, CD4+ lymphocytes are the dominant T cell in the reactive lymphoid tissues of patients not infected with HIV. In this study, lymph node biopsies from eight HIV-infected patients with persistent generalized lymphadenopathy syndrome (PGL) were assessed for IL-1 beta, IL-2, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF-beta) gene expression using the polymerase chain reaction (PCR). The cytokine gene expression of two cases of reactive adenopathy in patients not infected with HIV was assessed for comparison. IFN-gamma was expressed much more strongly in the PGL samples than in control reactive lymphoid tissues, whereas the other cytokines were expressed to a similar extent in both types of tissues. IFN-gamma may have an important role in maintaining the adenopathy of HIV infected patients. Expression of cytokines such as IL-2, IL-4 and IL-10 in HIV nodes may be adequate to allow the recruitment of naive B cells to the reactive process. PMID- 8467557 TI - IL-4 and interferon-gamma production in children with atopic disease. AB - In vitro studies have implicated reciprocal roles for IL-4 and interferon-gamma (IFN-gamma) in the regulation of IgE production. As elevated IgE is a major feature of atopic disease, an important question is whether an imbalance of IL-4 and IFN-gamma is present in vivo. The production of IL-4 and IFN-gamma in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell cultures from atopic children was examined to determine if there is an increased production of IL-4 and/or a reduced production of IFN-gamma. Highly atopic children with IgE > 600 U/ml produced significantly more IL-4 and less IFN-gamma in vitro than age-matched non-atopic controls. Production of IL-4 and IFN-gamma in mildly atopic children was equivalent to controls. These findings indicate that highly atopic children have an imbalance of IL-4 and IFN-gamma production and that the degree of imbalance relates to severity of the atopic state. The ratio of in vitro IL-4: IFN-gamma production correlated positively with serum IgE, which suggests that the balance of these two cytokines is a factor in the regulation of IgE, in vivo. It remains to be determined whether this imbalance of IL-4 and IFN-gamma in the highly atopic children is the cause or result of the disease process. PMID- 8467558 TI - Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy. AB - In the last few years many investigators have reported the recurrence of primary IgA nephropathy (IgAN) or the presence of persistent microhaematuria and/or proteinuria in family members of patients with IgAN. Our study was undertaken to investigate the relevance of abnormalities in the regulation of the IgA and IgM immune system in microhaematuric and asymptomatic family members of IgAN patients. Fifty-four out of 120 members of nine unrelated pedigrees were examined by urinalysis; polymeric IgA (pIgA), IgA rheumatoid factor (IgARF), IgA1-IgG immune complexes (IgA 1-IgG IC) and IgA 1-IgM IC, and other immunoglobulins were measured in serum samples. Moreover, we studied the production of immunoglobulins, pIgA and IgARF by peripheral blood mononuclear cells (PBMC) in basal conditions and after pokeweed mitogen (PWM) stimulation. Our data demonstrate that persistent microhaematuria was present in 24% of relatives. High serum levels of IgA, mainly pIgA and IgARF, IgA 1-IgG IC and IgA 1-IgM IC occurred in 66% of relatives. Abnormal spontaneous production of IgA by PBMC and after PWM stimulation was present in 64% of family members. Interestingly, high serum levels of IgM and abnormal production of this immunoglobulin by PBMC were observed in relatives. However, the immunological abnormalities did not correlate in any way with the presence of urinary abnormalities such as microhaematuria, which was most likely determined by an underlying glomerular alteration. PMID- 8467559 TI - Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients. AB - Increased levels of rheumatoid factors (RF) have been observed in the serum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9.7 ng/ml IgA RF, 11.6 ng/ml IgM RF and 64.6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21.4 ng/ml IgA RF, 21.4 ng/ml IgM RF, and 108.15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198.3 ng/ml of IgA anti-Fc(IgG) from involved versus 50.0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF (7.1 ng/ml IgA RF, 6.2 ng/ml IgM RF, and 42.3 ng/ml IgA anti Fc(IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened state of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF. PMID- 8467560 TI - Lower antibody response to tetanus toxoid associated with higher auto-anti idiotypic antibody in old compared with young humans. AB - The production of anti-tetanus toxoid (TT) antibody and anti-anti-TT (auto-anti Id) antibody has been measured in three young and three old persons. Both antibodies were measured using ELISA. We found that: (i) the anti-TT response of old subjects was lower than that of young subjects, (ii) serum auto-anti-Id antibody concentration was higher in old compared with young humans before boosting with TT, and (iii) anti-TT antibodies from different humans shared Id cross-reactivity when tested with a rabbit anti-Id antibody. Thus, the serum anti TT antibody response to boosting was inversely correlated with the serum level of auto-anti-Id. This conclusion is consistent with the view that the higher level of auto-anti-antibody in older subjects contributes to their impaired antibody response to TT. PMID- 8467561 TI - Augmentation by transferrin of IL-2-inducible killer activity and perforin production of human CD8+ T cells. AB - The effects of human transferrin (Tf) on lymphokine (IL-2)-activated killer (LAK) induction from blood lymphocytes of healthy donors was examined. LAK cells were induced by 6-day incubation in medium with recombinant human IL-2 of lymphocytes, and their cytotoxic activity was assessed by measuring 51Cr release from NK resistant Daudi cells. Tf alone did not induce any LAK activity, but in combination with IL-2, it augmented LAK induction dose- and time-dependently. This augmenting effect was completely abolished by pretreatment with anti-Tf antiserum. Tf augmented the proliferative response of lymphocytes to IL-2 and their expressions of receptors for IL-2 and Tf. CD8+ T cells were isolated from purified blood lymphocytes using antibody-bound magnetic beads. Addition of Tf to cultures of CD8+ cells resulted in significant augmentation of killer cell induction and perforin (PFP) production after 4 days stimulation with IL-2. These results indicate that Tf is important in generation of IL-2-inducible killer properties and PFP activity of human CD8+ T cells. PMID- 8467562 TI - Cytokines involved in the progression of multiple myeloma. AB - We have investigated which of the cytokines that are relevant in the in vitro growth of multiple myeloma (MM) malignant plasma cells are actually produced in vivo by MM patients. To this end, we have measured the levels of IL-1 beta, IL-3, IL-4, IL-6, IL-7, IL-8 and tumour necrosis factor-alpha (TNF-alpha) both in sera and in the supernatant of bone marrow (BM) stromal cell cultures from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The significance of our findings is three-fold. First, IL-6 and IL-8 are produced by MM BM stromal cells, while IL-1 beta, TNF-alpha, IL-4 and IL-7 are not. Second, IL-3 is the only cytokine consistently raised in serum samples: we have also detected low levels of serum IL-6 in a minority of cases, usually in advanced stage of the disease. Third, MM BM stromal cells are active IL-6 and IL-8 producers, while both normal and MGUS BM stromal cells are low producers, thus suggesting that in the BM of MM a number of environmental cells, that would normally be quiescent, are instead activated and that, in MM, activated BM stromal cells play an active role in supporting the progressive expansion of the B cell clone. PMID- 8467563 TI - Similar frequency of autoantibodies against 70-kD class heat-shock proteins in healthy subjects and systemic lupus erythematosus patients. AB - Stress or heat-shock proteins may be involved in the initiation and perpetuation of autoimmune diseases. In order to investigate a possible role of autoantibodies against the 70-kD family of heat-shock proteins in systemic lupus erythematosus (SLE), sera of SLE patients and healthy subjects were tested for the presence of IgG and IgM antibodies to 70-kD class proteins. These proteins were purified by affinity chromatography on ATP-agarose and used in Western blotting studies. The data obtained revealed that antibodies to the 72-kD and the 73-kD heat-shock proteins occurred with similar frequencies both in healthy subjects and SLE patients. Thus, approximately 20% of the sera in each group contained IgG antibodies, and IgM antibodies were detected in about 30% of the sera tested. Moreover, in SLE patients no association between the occurrence and titre of these antibodies and disease activity was found. These data suggest that antibodies to the 70-kD class heat-shock proteins are naturally occurring and argue therefore against an involvement of these antibodies in the pathogenesis of SLE. PMID- 8467564 TI - Interactions of anti-DNA antibodies with Z-DNA. AB - Systemic lupus erythematosus (SLE) sera, two classes of serum lipoproteins, and IgG antibodies from SLE and normal sera were tested for their reactivity with a Z DNA polymer, Br-poly (dG-dC). In all cases preferential binding to Z-DNA over B DNA was observed. This interaction, for the most part, could be inhibited by the negatively charged phospholipid, cardiolipin, which suggests that most of the anti-Z-DNA activity associated with sera arises from relatively non-specific ionic interactions between proteins and polyanionic molecules. An assay has been described that can eliminate proteins cross-reactive with negatively charged phospholipids. PMID- 8467565 TI - Significance of thyroglobulin antibodies cross-reactive with thyroperoxidase (TGPO antibodies) in individual patients and immunized mice. AB - Thyroglobulin (TG) and thyroperoxidase (TPO), both involved in thyroid hormone synthesis, represent major autoantigens in thyroid autoimmune disease. Despite numerous studies, the emergence, pathophysiological significance and role of autoantibodies to TG and TPO remain elusive. The recent identification of a new category of thyroid-specific autoantibody interacting with both TG and TPO (TGPO autoantibodies) offers a new opportunity in the study of thyroid autoimmunity. To gain a better insight into the significance of these TGPO autoantibodies, measurement in individual samples appeared necessary. The unique property of TGPO autoantibodies, simultaneous binding to TG and TPO, was used to set up a sandwich method which combined coated TG and radio-iodinated TPO. This method was found to be strictly specific for TGPO autoantibodies and sensitive enough to assay TGPO autoantibodies in serum. In humans, TGPO autoantibodies were found in most of the sera with high TG and TPO autoantibody titres, but not in sera negative for TG autoantibodies, whatever the TPO autoantibody titre. Furthermore, high TGPO autoantibody titres were found in sera strongly cytotoxic for cultured porcine thyroid cells. However, significant correlation of TGPO autoantibody titre was observed neither with TG and TPO autoantibody titres (n = 48) nor with complement dependent cytotoxicity (n = 50). TGPO antibody assay was also performed in individual plasma of CBA/J mice immunized with either human TG (n = 6) or human TPO (n = 6). Immunization with TG induced high levels of not only TG but also TGPO antibodies, which exhibited a strong reactivity for TPO and whose binding to TG and TPO was fully inhibited by TG. In contrast, immunization with TPO induced high levels of only specific TPO antibodies accompanied by low levels of specific TG antibodies. In this case TGPO antibodies were not detected. Of note, TG- and TPO-immunized mice mounted an immune response against their own TG, but did not exhibit histological signs of thyroiditis. Large panels of TG and TPO MoAbs were also investigated with this method: 18/25 TG MoAbs and only 1/13 TPO MoAbs were found cross-reactive. Taken together, these data provide evidence that TGPO antibodies are effectively present in individual patients and TG-immunized mice, are different from specific TG and TPO antibodies, and may derive from natural B cell repertoire by autoimmune processes involving TG and not TPO. PMID- 8467566 TI - Characterization of cytokine production in infectious mononucleosis studied at a single-cell level in tonsil and peripheral blood. AB - Cytokine profile and production was studied at a single-cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine-specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL-1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5, IL-6, IL-10, GM CSF, tumour necrosis factor-alpha (TNF-alpha) or TNF-beta, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti-CD3 MoAbs for 2-3 h restimulation under conditions which did not activate normal cells. By this approach 168 +/- 120 cells/10,000 peripheral blood mononuclear cells produced IFN-gamma as compared with 10 +/- 8 cells/10,000 non-stimulated cultured cells obtained from IM patients (P < 0.001) and 1/10,000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-beta was detected in IM cells obtained from peripheral blood by this restimulation. In contrast, a spontaneous cytokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160 +/- 40 cells/10,000 cells produced IL 2, 40 +/- 30 cells IL-6, 30 +/- 30 cells TNF-beta and 35 +/- 25 cells IFN-gamma, respectively. No such spontaneous IL-2, IL-6, TNF-beta or IFN-gamma production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia. PMID- 8467567 TI - Autoantibodies in malaria, tuberculosis and hepatitis B in a west African population. AB - Following reports of associations between autoantibodies and living in the tropics, we have studied the seroprevalence and nature of anti-nuclear antibodies, anti-cardiolipin antibodies, antibodies to extractable nuclear antigens and anti-neutrophilic cytoplasmic antibodies in 351 West Africans with malaria, tuberculosis or hepatitis B, or in good health. Amongst healthy West Africans we found a seroprevalence of 7% for anti-nuclear antibodies with several staining patterns, and of 30.3% for anti-cardiolipin antibodies. Among patients with tuberculosis and malaria there was twice that frequency of anti-nuclear antibodies (predominantly speckled in pattern), and anti-neutrophil cytoplasmic antibodies (predominantly IgM) were demonstrated in a few cases. A possible association between IgG anti-cardiolipin antibodies and tuberculosis was observed (P < 0.05), but antibodies to double-stranded DNA were not elevated and no antibodies to extractable nuclear antigens were found in any of the patients or healthy individuals studied. Our findings suggest the need for caution in the interpretation of autoantibody tests in subjects from or living in the tropics, as well as in patients with tropical infections. PMID- 8467568 TI - An immunohistochemical analysis of onchocercal nodules: evidence for an interaction between macrophage MRP8/MRP14 and adult Onchocerca volvulus. AB - We have used a panel of MoAbs to investigate the phenotype of macrophages and other leucocytes infiltrating onchocercal nodules. Nodules were removed from individuals at the end of the second year of a community-based, placebo controlled trial of annual ivermectin chemotherapy in northern Nigeria. No significant differences were seen in the distribution and phenotype of leucocytes in nodules from ivermectin- and placebo-treated individuals. Live adult worms were only seen in nine of the 21 nodules examined. Three regions were clearly discernible within nodules containing both live and dead worms; an outer fibrovascular capsule (zone A), an inner adult worm bundle with surrounding hyaline extracellular matrix interspersed with solitary cells (zone B), and a dense cellular infiltrate surrounding and in contact with a variable proportion of the worm (zone C). Macrophages were the predominant cell type in all zones of the nodule. Those in zone B were distinguished by their dendritic morphology and strong reactivity with MoAbs directed against class II molecules, FcRI (CD64) and CD68, whereas macrophages in zone C were larger, more heterogeneous in shape, and were distinguished by strong reactivity with MoAbs directed against CR4 (CD11c, CD18) and MRP8/MRP14, and with MoAb24. T cells were found primarily in zones A and C, whilst eosinophils were found in only six nodules. A unique staining pattern was seen using MoAbs reacting with the calcium-binding protein MRP8/MRP14. Most macrophages in zones A and B were negative; however, where the occasional positive macrophage was seen in zone B, MRP8/MRP14 was also found around the cell and on the neighbouring worm surface, giving the impression that MRP8/MRP14 was being secreted onto the adult worm. Macrophages in zone C were also MRP8/MRP14-positive, and often the whole infiltrate was surrounded with extracellular MRP8/MRP14, with greatest concentration seen adjacent to the worm. MRP8/MRP14 was not identified on the surface of microfilariae (MF) within the same nodules. Since MRP8/MRP14 was seen on the adult worm in the absence of a leucocytic infiltrate, it may have an early role to play in the immune response to Onchocerca volvulus. PMID- 8467569 TI - The angiotensin-converting enzyme inhibitor, perindopril, prevents cardiac hypertrophy in low-renin hypertensive rats. AB - 1. To examine whether an angiotensin-converting enzyme (ACE) inhibitor prevents left ventricular (LV) hypertrophy even in low-renin hypertension, we studied the effect of the administration of perindopril on cardiac hypertrophy induced by partial renal ablation in hypertensive rats. 2. Rats that had undergone partial nephrectomy were randomly divided into four groups that received the following as drinking water: Group A, tap water; Group B, 1% sodium chloride (NaCl); Group C, NaCl + perindopril 3 mg/kg per day; and Group D, NaCl + perindopril 1 mg/kg per day. Plasma renin activity (PRA), angiotensin-II (AII) concentration and cardiac tissue AII were measured. 3. Supplementation of NaCl following nephrectomy increased the blood pressure and cardiac weight compared with rats that had undergone nephrectomy alone (P < 0.05). Treatment with perindopril (3 mg/kg per day) did not affect the blood pressure and plasma AII but inhibited the increase of cardiac weight (P < 0.05). Left ventricular AII was decreased in cases of reduced renal mass hypertension, but was not changed by treatment with perindopril. 4. These results demonstrate that perindopril may be able to prevent LV hypertrophy even in low-renin hypertension, which was not mediated by a reduction of blood pressure or suppression of the circulating and cardiac renin angiotensin systems. Other mechanisms of ACE inhibitors may contribute to the cardioprotective effects. PMID- 8467570 TI - The inhibition of nitric oxide-mediated relaxations in rat aorta and anococcygeus muscle by diphenylene iodonium. AB - 1. The effects of diphenylene iodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate-dependent oxidases (which generate superoxide anions), were studied on nitric oxide (NO)-mediated responses in isolated preparations of the rat aorta and anococcygeus muscle. 2. In aortic rings, the endothelium-dependent relaxant action of acetylcholine was reduced by DPI (0.3-10 mumol/L) in a concentration-dependent manner and abolished by the NO synthase (NOS) inhibitor L-nitro-NG-arginine methylester (L-NAME; 100 mumol/L). Relaxations induced by sodium nitroprusside (SNP) or NO were not affected by DPI or L-NAME. 3. In anococcygeus muscles, DPI (0.3-10 mumol/L) as well as L-NAME (5 100 mumol/L) produced concentration-dependent reductions of relaxations produced by nitrergic nerve stimulation. Relaxations induced by NO and SNP were not affected by either DPI or L-NAME. L-Arginine (1 mmol/L) prevented the reduction of nitrergic relaxations by L-NAME but not by DPI. 4. Contractions of anococcygeus muscles elicited by exogenous noradrenaline (1 mumol/L) were not affected or were inhibited by DPI (0.3-10 mumol/L), but the contractions elicited by noradrenergic nerve stimulation were significantly enhanced by DPI and L-NAME. When noradrenergic contractions had already been maximally enhanced by L-NAME (100 mumol/L), DPI produced no further enhancement. L-Arginine (1 mmol/L) prevented the enhancement of noradrenergic contractions by L-NAME but not by DPI. 5. The efflux of radioactivity induced by field stimulation from anococcygeus muscles previously incubated with [3H]-noradrenaline was not affected by either DPI or L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467571 TI - Circadian variations of blood pressure and pulse rate in essential hypertensives with diabetes mellitus. AB - 1. The circadian variations of blood pressure and pulse rate in essential hypertensives either with or without diabetes mellitus were studied. 2. Diabetic patients with orthostatic hypotension showed an increase in variability of blood pressure and a decrease in that of pulse rate when assessed by coefficient of variation. Cosinor analysis showed no significant circadian rhythm in both blood pressure and pulse rate in these patients. 3. There were no differences in the circadian variations of blood pressure and pulse rate between essential hypertensives with and without diabetes mellitus unless orthostatic hypotension was present. 4. These results suggest that diabetes mellitus per se does not have any effects on the circadian variations of blood pressure and pulse rate in essential hypertensives unless autonomic neuropathy is present. PMID- 8467572 TI - Decreased norepinephrine content in the medulla oblongata in severely hypertensive rats. AB - 1. To clarify possible abnormalities in catecholamines in the medulla oblongata in relation to severe hypertension, the authors measured changes in catecholamine levels in the medulla oblongata of malignant stroke-prone spontaneously hypertensive rats (M-SHRSP). Effects of the adrenal medullae and peripheral nerves were ruled out by adrenal demedullation and chemical sympathectomy. 2. The level of norepinephrine in the medulla oblongata was significantly lower in untreated M-SHRSP than in untreated WKY (control) rats at 10 weeks of age. Further, it was significantly lower in treated M-SHRSP than in the treated WKY group at both 6 and 10 weeks of age. The level of epinephrine in 6 week old treated M-SHRSP was significantly higher than that in age-matched treated WKY, but no other differences were observed in terms of epinephrine content. There were no age- or treatment-related differences in dopamine levels in the medullar oblongata. 3. Since norepinephrine has an inhibitory effect on blood pressure elevation in the nucleus tractus solitarii (NTS) in the medulla oblongata, the suppression of negative feedback due to a decrease in the activity of inhibitory neurons in the medulla oblongata appears to be involved in the development and progression of severe hypertension in M-SHRSP. PMID- 8467573 TI - Biliary hyperpressure in rat extrahepatic cholestasis alters horseradish peroxidase biliary excretion. AB - 1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n = 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467574 TI - A study on the role of cholinergic and gamma amino butyric acid systems in the anti-nociceptive effect of gossypin. AB - 1. The participation of cholinergic and gamma amino butyric acid (GABA) neurotransmitter systems in the anti-nociceptive effect of gossypin was investigated using pharmacological tools. 2. Physostigmine potentiated its anti nociceptive response while atropine failed to modify it significantly. 3. THIP (4,5,6,7-tetra hydroisoxazolo (5,4-C) pyridin-3-ol) and gossypin treatment produced an additive response while bicuculline attenuated the anti-nociceptive response of gossypin. Similar observations were recorded for morphine. 4. It is suggested that cholinergic and GABAergic systems play a role in gossypin-induced anti-nociception. PMID- 8467575 TI - Novel microscopy using fibre optic confocal imaging and its suitability for subsurface blood vessel imaging in vivo. PMID- 8467576 TI - Differences in the expression of spondyloarthropathy: a comparison between ankylosing spondylitis and psoriatic arthritis. AB - The aim of the study was to compare the spondyloarthropathy of ankylosing spondylitis (AS) to that of psoriatic arthritis (PsA). Forty patients with AS and 66 patients with PsA underwent a complete assessment according to a standard protocol, including radiographic evaluation and HLA typing. A logistic regression analysis was performed controlling for age, arthritis duration, and sex. A higher frequency of inflammatory neck and back pain and stiffness (p < 0.0002), limitation of back movements (p < 0.0006), grade 4 sacroiliitis (p = 0.007), and syndesmophytes (p = 0.005) was noted in AS, while peripheral arthritis was more common and more severe in patients with PsA (p = 0.002). A lower frequency of HLA B17 (p = 0.02), and a higher frequency of HLA B27 (p = 0.0001), and Cw2 (p < 0.01) was found in AS compared to PsA. Thus, there are clinical, radiologic, and genetic differences in disease expression of the SA of AS and PsA, supporting their classification as distinct entities. PMID- 8467577 TI - Uptake of ferritin by isolated rat hepatocytes. Effect of metabolic inhibitors and iron. AB - To further characterize the hepatic endocytic pathway of ferritin, the effects of inhibitors of intracellular dissociation of ligands (monensin 15 microM, chloroquine 400 microM), intracellular proteolysis (leupeptin 100 microM) and iron loading on the endocytosis of 125I-rat liver ferritin were studied in isolated rat hepatocytes. Cell associated radioactivity at 37 degrees C was decreased by 27% with chloroquine and 18% with monensin after 4 h. Cell associated radioactivity increased by 38% with leupeptin at 37 degrees C. Acid soluble radioactivity in the extracellular medium was significantly decreased at 4 h in the leupeptin group, which suggests that leupeptin inhibited the lysosomal degradation of the 125I-ferritin resulting in intracellular accumulation of ligand rather than increased uptake of ferritin. Iron loading of cells (5.4-fold increase in intracellular iron) did not significantly alter the binding or accumulation of 125I-ferritin. The characteristics of the endocytic pathway for ferritin are more similar to the asialoglycoprotein receptor than the transferrin receptor, and the hepatic uptake of ferritin is unaffected in this study by increasing the intracellular iron concentration. PMID- 8467578 TI - Middle cerebral artery blood flow velocity in the newborn following delivery. AB - Ninety-five normally grown term and preterm newborns were examined to determine the means and prediction limits of cerebral blood flow velocity following delivery and to examine the relationship of systemic blood pressure to cerebral blood flow velocity. Doppler blood flow velocity was observed during the four days following delivery. Continuous measures of blood pressure and heart rate were recorded concurrently. Mean peak systolic and end diastolic blood flow velocity immediately following delivery was 43.2 and 9.3 cm/sec for term newborn, and 31.8 and 3.3 cm/sec for preterm newborn. During the 24 h following delivery there was no change of peak systolic blood flow velocity but a two to three fold increase of end diastolic blood flow velocity in the term and preterm newborn. The reference limits for peak systolic and end diastolic blood flow velocity provide criteria to define abnormal increases and decreases of blood flow velocity. During the 24 h following delivery, increasing diastolic blood pressure was associated with increasing end diastolic blood flow velocity independent of birth weight and time following delivery. Also there was a significant correlation between systemic pressure pulsatile index and middle cerebral artery blood flow velocity pulsatile index. Thus systemic blood pressure pulsatility must be recognized as distinct from other intracerebral influences on cerebral blood flow velocity regulation in the newborn. PMID- 8467579 TI - Bacteremic community-acquired pneumonia due to viridans group streptococci. AB - We studied 1118 patients with community-acquired pneumonia who were admitted to our hospital over an 8-y period. Seventy-six of the 1118 patients were bacteremic and 7 (9.2%) of these had blood cultures positive for various viridans streptococci. Four had polymicrobial bacteremia (S. mitis, S. sanguis 1, S. sanguis II; S. mitis, S. sanguis II; S. MG; S. sanguis II, Neisseria sp; S. intermedius, S. aureus). For 3 of the 7, viridans streptococci were the only agents implicated in the etiology of the pneumonia. These patients were classified as definite viridans streptococcal pneumonia; the remaining 2 were probably and 2 were possibly due to these micro-organisms. The 5 males and 2 females had a mean age of 61.8 y. The mortality rate was 28%. All were febrile and had elevated white blood cell counts. The 5 who had arterial blood gas measurements performed were hypoxemic pO2 34-68 torr. The chest radiographs were not distinctive--a segmental alveolar opacity was the most common abnormality. We conclude that viridans streptococci rarely cause bacteremic community-acquired pneumonia. There are no distinctive clinical or radiographic features of this type of pneumonia. PMID- 8467580 TI - The absorption and bioactivity of bacterially synthesized menaquinones. AB - After optimizing conditions for maximal production of menaquinones (MK), S. aureus and B. vulgatus were grown in batches, harvested and extracted for qualitative and quantitative MK content utilizing HPLC (high performance liquid chromatography) until a total of 6 mg was available. Five normal healthy male volunteers were placed on a vitamin K1 deficient diet (< or = 25 micrograms/day) and were subsequently warfarinized to maintain a prothrombin time (PT) 1.5-2 times control. Following stabilization of daily warfarin dosage 1 mg doses of the extracted MK were orally administered. As a control, the same volunteers were later warfarinized but no MK was given. Within 24 h of MK administration the prothrombin time (PT) decreased (mean +/- SEM) 3.6 +/- 1.0 s (p < 0.005) and the Factor VII level increased 0.36 +/- 0.3 u/ml (p < 0.005) vs a PT increase of 1.0 +/- 1.0 s (p > 0.1) and a Factor VII level increase of 0.03 +/- 0.1 u/ml (p > 0.1) in the control phase. Within 48 h of MK administration the PT was normal in all subjects but remained > or = 1.5 times control in the control phase. These data demonstrate for the first time the absorption and bioactivity of bacterially synthesized vitamin K in humans. PMID- 8467581 TI - Parathyroid hormone: regulation of synthesis and secretion. AB - Calcium homeostasis is essential for survival and is primarily achieved through the actions of parathyroid hormone. Parathyroid hormone secretion and synthesis are primarily regulated by serum calcium levels, although other factors such as vitamin D and neurotransmitters play a role. This review is intended to provide the reader with up to date information on the current state of basic cell regulation research into parathyroid function. While some mention of disease states is made, the focus of this review is on the calcium regulation of parathyroid hormone secretion at the molecular level. Individual sections will discuss calcium-sensing, signal transduction by calcium and other secretagogues, regulation of parathyroid hormone synthesis, and strategies of regulation of parathyroid hormone secretion by calcium. Particular emphasis is given to the calcium-stimulated degradation of parathyroid hormone within the parathyroid as one of the major pathways by which circulating levels of bioactive hormone are controlled. PMID- 8467582 TI - Are contemporary methods for somatic gene therapy suitable for clinical applications? AB - Clinical trials involving the introduction of recombinant genes into human subjects began in 1989 after a decade of earnest debate concerning the technical, social, and ethical implications of somatic gene therapy. The initial trials involved the introduction of recombinant genes into peripheral blood lymphocytes to study the characteristics of tumor infiltrating lymphocytes, enhance immunotherapy for cancer, and treat severe combined immunodeficiency due to adenosine deaminase deficiency. Additional clinical trials involving the introduction of genes into bone marrow, hepatocytes, and tumor cells are underway. Are these clinical trials premature? This article reviews basic methods for somatic gene therapy and the clinical trials which have been proposed or performed to date. This clinical experience suggests that gene therapy can be performed in select clinical trials safely and with public acceptance. Clinical trials have provided essential data concerning the feasibility and safety of gene transfer in human subjects. These trials have also brought a clinical focus to the assessment of technologies currently being used in experimental models. While there will certainly be significant advances in somatic gene therapy in the future, existing methods may be employed fairly in clinical trials. PMID- 8467584 TI - Brachial plexus injury. Postgraduate Boerhaave course. Leiden, March 25-26, 1993. PMID- 8467583 TI - Ferguson's BCG research--Canada's first randomized clinical trial? PMID- 8467585 TI - Brachial plexus injuries. PMID- 8467586 TI - Peripheral nerve lesions: the neuropharmacological outlook. AB - A review is presented of compounds with trophic effects on the peripheral nervous system. A distinction should be made between three types of effect: enhancement of neurone survival, stimulation of regeneration and induction or stimulation of collateral sprouting. On the basis of data currently available, laminin and insulin-like growth factor I are the most promising substances for regeneration of peripheral nerve lesions. Future investigations of laminin should provide an answer to the query whether local administration facilitates sprouts to cross the gap between proximal and distal nerve stumps. Further experiments are required on effects of systemic administration of IGF-I in animal models of peripheral nerve lesions before investigations can be initiated in man. PMID- 8467587 TI - Functional recovery after ventral root avulsion and implantation in the spinal cord. AB - This survey describes experiments performed in rats, cats and monkeys aiming at the management of motor deficits after ventral root rupture or avulsion from the spinal cord as seen in brachial plexus lesions. After intramedullary implantation of the ruptured or avulsed ventral root, neurophysiological data show that alpha and probably also gamma motoneurons are capable of producing new axons which regrow for a considerable distance in the spinal cord before entering the implanted root. Intracellular physiological experiments demonstrate that new axons can conduct action potentials and elicit muscle responses. The neurons are reconnected in segmental spinal cord activity and respond to impulses in sensory fibres. In primates, implantation of avulsed ventral roots in the brachial plexus resulted in functional restitution. It is concluded that intraspinal implantation of avulsed ventral roots significantly promotes motor recovery in the muscles supplied by the lesioned spinal cord segments. These studies indicate the possibility of surgical treatment of ventral root avulsion injuries in brachial plexus lesions in man. PMID- 8467588 TI - Reimplantation of ventral rootlets into the cervical spinal cord after their avulsion: an anterior surgical approach. AB - Root avulsions from the cervical spinal cord due to traction injuries are beyond repair up to the present day. An anterior surgical approach has been developed in cats for reimplantation of the ventral rootlets into the site of avulsion. The consecutive surgical steps towards exposure of the ventral surface of the cervical cord are given in detail. The morphological relations during the operative procedure are explained in the text and by illustrations. In this study the surgery related mortality rate was 16% and the overall mortality rate amounted to 21%. Loss of blood, initially a major problem, was coped with by increasing technical experience and the infusion of plasma expanding fluid. In 2 animals with survival times of 209 and 293 days respectively, many ventral horn motoneurons were found HRP-positive after retrograde HRP transport through the site of reimplantation. The findings provide evidence that the axonal continuity between reimplanted ventral roots and their motoneurons may be restored. PMID- 8467589 TI - The topographical anatomy of the brachial plexus. AB - The anatomy of the shoulder region is discussed focusing on the course of the brachial plexus. Magnetic resonance imaging enables one to visualize the topographical anatomy of this area. PMID- 8467590 TI - The dorsoscapular nerve in traumatic brachial plexus lesions. AB - The origin and course of the nerval innervation of the levator scapulae and rhomboid muscles was studied in four human cadavers. Special attention was given to surgical anatomy. The levator scapulae muscle receives two small segmental nerves from C3 and C4, respectively. The rhomboid muscle receives two segmental nerves, one from C4 and the other from C5. Moreover, in a series of 137 patients with a traumatic brachial plexus lesion, the linkage between levator scapulae and rhomboid muscle function impairment and site of the brachial plexus lesion was studied. Paresis of one or both of these muscles was noted in 13 cases. It was concluded that the rhomboid muscle may function on a single C4 nerve supply without any loss of strength. Arguments are put forward to support the relevance of rhomboid muscle testing in the assessment of brachial plexus lesions. PMID- 8467591 TI - Mechanisms of brachial plexus lesions. AB - The main causes of brachial plexus palsies are traction, due to extreme movements, and heavy impact. In downward traction of the arm and forcible widening of the shoulder-neck angle the lesion will occur in the upper roots and trunk. Forcible upward traction will cause avulsion of T1 and C8. The most violent trauma will result in a lesion at all levels. Rupture of the cords and/or individual infraclavicular nerves will be produced by traction and/or forcible widening of the scapulohumeral angle. Vascular structures are subjected to the same mechanism and injuries of these structures give information about the site and severity of nerve lesions; fractures of the skull, cervical spine, clavicle, first rib or arm yield further data on the mechanism of trauma that has produced the brachial plexus palsy. Heavy impact or crush lesions are caused by direct trauma to the (supra)clavicular region and are nearly always associated with fracture of the clavicle. PMID- 8467592 TI - A rostrocaudal somatotopic organization in the brachial dorsal root ganglia of neonatal rats. AB - A rostrocaudal somatotopic organization in the rat lumbar dorsal root ganglia (DRGs) during development has been demonstrated. The present study shows that such a rostrocaudal somatotopic organization also exists in the brachial DRGs of neonatal rats. WGA-HRP or WGA-HRP/HRP injections into the forepaw of neonatal rats gave rise to completely and partially labeled DRGs. Partial labeling always concerned the caudal or rostral halves of the rostral-most or caudal-most labeled DRGs, respectively. Labeling of forelimb nerves (cutaneous branch of the musculocutaneous nerve, median and ulnar nerve) in neonatal rats also resulted in whole labeled DRGs and labeled rostral or caudal halves of DRGs. Accordingly, just as was found for the hind limb nerves, the position of the somata of the sensory neurons of forelimb nerves can be restricted to the rostral or caudal half of a DRG. Moreover, it was observed that the rostrocaudal organization in the brachial DRGs is maintained in the spinal nerves. Application of tracer to the cut end of intercostal nerves in neonatal rats produced labeling of one whole thoracic DRG. It is therefore possible that the rostrocaudal organization in the brachial and lumbar DRGs is a consequence of the formation of the plexuses. In one instance a subdivision in the labeling pattern of a midthoracic DRG was noticed after a WGA-HRP injection into the thoracic wall of a neonatal rat. The whole thoracic DRG was labeled except the dorsorostral corner. This indicates that during development, some kind of somatotopic organization may exist also in the thoracic DRG. PMID- 8467594 TI - The tensile testing machine applied in the study of human nerve rupture: a preliminary study. AB - A tensile testing machine was used to provoke lesions of fixed and unfixed brachial plexus nerves. The forces and mechanical work were measured before and during rupture. Fixed nerves resist continued tensile forces better than unfixed nerves do. Increasing the speed of the tensile forces results in a decrease of the extension a brachial plexus nerve can withstand. The mechanical work needed to start rupture is equal to the mechanical work used to complete rupture of the nerve. PMID- 8467593 TI - Brachial plexus injury in multitraumatized patients. AB - The majority of patients presenting with a brachial plexus traction injury suffer from multisystem trauma. The consequences are discussed. Occlusion of the axillary artery is an associated lesion which rarely produces ischaemia of the upper limb. Repair may preferentially be carried out together with elective plexus reconstructive surgery. PMID- 8467595 TI - Neuroradiological investigations in cervical root avulsion. AB - Cervical myelography in combination with CT myelography is not fully reliable to demonstrate a partial or complete cervical root avulsion. MRI scanning can demonstrate large traumatic meningoceles or additional lesions, such as intramedullary or extradural haematomas, but not a root avulsion. In experimental conditions MR microscopy enables visualization of the avulsed root separated from the spinal cord. The anterior funiculus shows transverse tracts left behind by the avulsion at the original site of the motor fibres. However, the small bore of the current high field magnets and the very long acquisition time makes this method, as yet, unsuitable for application in man. PMID- 8467596 TI - Ultrastructural study on avulsion effects of the cat cervical moto-axonal pathways in the spinal cord. AB - After selective avulsion of the ventral root cervical 7 (C7) from the adult cat spinal cord, the intraspinal trajectories of the torn axons in the white matter were studied at different survival times. Two phases could be discerned: an early phase which showed changes that occurred up to 14 days after avulsion and a second phase from day 30 onwards. Two days postoperatively, considerably swollen, empty myelin sheaths occurred, which remained present up to 14 days after avulsion. A primary increase in the number of glial cells (microglia) was noted on days 2 and 4 after avulsion. Ultrastructurally, unmyelinated and myelinated terminal clubs were found 8 and 14 days after avulsion. These clubs were characterized as cones of growth, related to axonal regeneration. A second glial increase was present after 30 days. At that time, the entire moto-axonal pathway clearly showed a degeneration pattern. This finding was light microscopically confirmed by an increase of GFAP-positive astrocytes. During the first 30 days, a front of small calibre myelinated axons, starting at the transition zone of the grey and white matter traversed halfway through the moto-axonal pathway. However, on days 60 and 90 no further shift of the front had occurred. PMID- 8467597 TI - Computer assisted diagnosis and treatment planning of brachial plexus injuries. AB - PLEXUS is a computer program which has been developed to provide recommendations for diagnosis and treatment planning of brachial plexus injuries. This computer program is meant for neurologists, neurosurgeons and orthopaedic surgeons who are not experienced in the field of brachial plexus injuries. The system detects the locations and severity of brachial plexus lesions. PLEXUS also indicates whether the patient may be referred to a specialist centre for nerve surgery. In order to determine whether the advice given by the system is of expert quality, a study of its recommendations is being carried out in cooperation with four international brachial plexus experts. To investigate if the system does indeed have the capability to assist physicians in the area of brachial plexus injuries, it is being tested clinically in four hospitals in The Netherlands. PMID- 8467598 TI - Lesions found when operating traction injuries of the brachial plexus. AB - Traumatic traction injuries occurring mostly during road traffic accidents frequently cause severe lesions of the brachial plexus. 108 patients with such lesions were surgically explored in the last 5 years by one surgeon. By contrast, 101 patients with other lesions to the brachial plexus or various injuries to neighbouring nerves were operated on during the same period. Among the former, root avulsions were found in 73 patients, 33 presenting with 4 or all roots avulsed. In 14 of these patients the subclavian artery was ruptured. Out of 17 patients with infraclavicular distal plexus lesions 7 presented with a rupture of the axillary artery. The severity of the lesions to nerves and vessels in the shoulder girdle region seems to have increased over the past 10 years. The different injury patterns seen at operation are presented. PMID- 8467599 TI - Surgical repair of brachial plexus injury. AB - This preliminary report surveys the authors' experience in the treatment of 66 patients with brachial plexus traction injuries. The results of nerve reconstructive surgery obtained in 44 patients with a follow-up of at least 2 years were disappointing; on average, 10% of upper limb function was added. The role of several factors involved in this type of injury and the major draw-backs of treatment are discussed in combination with future possibilities. Current techniques of neurotizations are presented in one case. PMID- 8467600 TI - Obstetric brachial plexus lesions and their neurosurgical treatment. AB - The present series of 655 brachial plexus lesions includes 240 obstetric palsies. The results of neurophysiological and radiological examinations in these cases are often disappointing in regard to the evaluation of the severity of the lesion. Timing for surgery was according to the criterium of Gilbert: lack of clinical signs of recovery of the biceps at the end of the third month. Intra- and/or extraplexal neurotizations were performed in 94 children. Although only 28 children operated upon have been followed up for at least 2 years, some tentative conclusions may be drawn. A good to very good result was achieved in 10 children with an upper plexus lesion, born in cephalic presentation. In breech presentation cases, often associated with root avulsion, and in (sub)total lesions, the final result was much less. PMID- 8467601 TI - Perineurial cells are the first to traverse gaps of peripheral nerves in silicone tubes. AB - Silicon tubes were used to study the outgrowth and differentiation of the perineurium around the cord bridging the gap between the proximal and distal stumps of the transected sciatic nerve of rats. The sequence of events was investigated at time intervals 3, 7, 12, 18, and 21 days after surgery. Although similar tubulation systems have been used to investigate various aspects of peripheral nerve fibre regeneration, the present study shows for the first time with electron microscopic and immunocytochemical methods that a primitive perineurium bridges the gap as the initial cellular element. This perineurium develops from outgrowing fibroblasts as early as 7 days post surgery, forming a tube which is used as a guiding structure for subsequent cellular elements. The proximal and distal perineurial tubes join between 12 and 18 days after surgery thus representing the first connection between the proximal and distal nerve stumps. Blood vessels, Schwann cells, and axons appear to follow in this sequence. PMID- 8467602 TI - Nerve growth factor and regeneration of peripheral nervous system. AB - Nerve growth factor, a well-known neurotrophic factor, supports the survival, differentiation and maintenance of sensory and sympathetic neurons during embryonic development and in the adult. This paper summarises the data on its involvement in peripheral nerve regeneration. PMID- 8467603 TI - Muscle transpositions in the shoulder and upper arm for sequelae of brachial plexus palsy. AB - Permanent deficiency in abduction and external rotation of the arm seen after brachial plexus injury may be corrected by a levator scapulae transposition onto the supraspinatus, while the teres major, associated or not with latissimus dorsi, is transferred onto the infraspinatus muscle. Transposed in a bipolar manner, the latissimus may compensate the deltoid muscle. Associated measures have to be carried out in children with deformities caused by obstetrical palsy. A paralysed serratus anterior is best compensated by a transfer of the pectoralis major together with pectoralis minor muscle. PMID- 8467604 TI - Musculo-tendinous transfers of the hand and forearm. AB - The concept of providing a more equitable distribution of forces acting upon a disabled limb is the basis of tendon transfers. The musculo-tendinous transfer is usually performed by moving the insertion, thereby altering the direction of the unit in an attempt to replace a lost function. In order to obtain a successful result basic principles have to be followed. The transferred muscle must have enough strength, should have approximately the same amplitude as the muscle whose function it is replacing and should have a straight line of pull from the origin to the new insertion or distally from the newly created pulley. Furthermore, the nerve and blood supply should remain intact during the actual transfer. In the event of scarred tissue or poorly mobilized joints treatment should first deal with these problems before tendon transfer is carried out. After careful assessment of the patient's disability a plan of operation can be conceived on the basis of the extent of functional loss balanced against the muscle force available for transfer. Essential for forearm and hand function are wrist extension and finger flexion as well as thumb and intrinsic function. The loss of these functions may be compensated for by a variety of motors. The choice is made on the basis of the available possibilities and the demands of the patient. To obtain optimal postoperative results physiotherapy of the hand and a well motivated patient are necessary. PMID- 8467605 TI - Respiration-related activity in the biceps brachii muscle after intercostal musculocutaneous nerve transfer. AB - Needle EMG and polygraphic recordings of respiration and biceps activity were obtained in 7 patients who had undergone intercostal to musculocutaneous nerve transfer because of severe traumatic injury to the brachial plexus. EMG activity during expiration and inspiration was assessed during quiet breathing, deep breathing, and during sustained inspiration and expiration, and compared to the clinical strength of the biceps muscle. Biceps activity was consistently found during both expiration and inspiration, and in either case separately related to the flexion force levels. Initially this relationship appeared equally strong for both phases. With time, control over flexion changes from a completely respiratory-driven control to a conscious volitional control; however, involuntary effects of respiration always remained present in polygraphic recordings. Theoretical explanations for the change in control are put forward. PMID- 8467606 TI - XIIIth European Workshop for Rheumatology Research. Brighton, UK, 28-30 January 1993. Abstracts. PMID- 8467607 TI - The occurrence of fibromyalgia-like syndromes in a general female population. AB - In an epidemiological survey of females aged 20-49 years in Arendal, Norway, 217 persons with musculoskeletal pain were examined for the presence of fibromyalgia as defined by the ACR criteria of 1990. Forty females with fibromyalgia were found whereas 129 females had chronic musculoskeletal pain of more than three months duration but failed to meet the criteria. Two females suffered from nonrheumatic disorders which could explain their musculoskeletal pain. Forty-six females had pain of less than three months duration. Somewhat surprising, the presence of tender points and symptoms regarded as typical of fibromyalgia were rather frequently observed among the females who failed to satisfy the ACR 1990 criteria. No other diseases were found which could explain their complaints or clinical findings. The presence of fibromyalgia-like syndromes is suggested, and the classification and nature of such syndromes are discussed. PMID- 8467608 TI - Association of anti-cardiolipin antibodies with vascular thrombosis and neurological manifestation of Behcets disease. AB - We have studied 44 patients with Behcet's Disease (BD) to look for any correlation of arterial and venous thrombosis or central nervous system (CNS) manifestations with anti-cardiolipin antibodies (ACLA). Twenty patients were positive for ACLA by MELISA method. Ten patients had IgG antibody, four had IgM and six had both IgG and IgM. Of these patients, 11 had a history of vascular thrombosis and thrombophlebitis and nine had CNS manifestations. The association of ACLA with vascular thrombosis or CNS manifestation of Behcet's disease was statistically not significant. PMID- 8467609 TI - Complement split product C3d as an indicator of disease activity in systemic lupus erythematosus. AB - In order to investigate, if complement levels can be used as an indicator of clinical activity in systemic lupus erythematosus (SLE), levels of C3, C4, CH50, and C3d were measured in 79 patients, 41 with inactive, 31 with moderately active and 7 with severely active disease. Our study shows that C3d, and particularly the C3d/C3 ratio, provide sensitive markers for disease activity in SLE. Since C3d is a direct measurement of complement turnover, it reflects complement activation better than C3, C4 and CH50. PMID- 8467610 TI - Protrusio acetabuli in juvenile rheumatoid arthritis. AB - Acetabular protrusion (PA) as measured by a line crossing method was studied in 73 patients with juvenile rheumatoid arthritis (JRA) and its frequency found to be 12% (9/73), presenting bilaterally in 5 cases and unilaterally in 4. All patients had some other forms of radiological damage and the presence of PA was predominantly observed in the JRA group with greater age at onset (8 vs 4.2 years; p < 0.001) and lower frequency of extraarticular manifestations (22% vs 72%; p < 0.01). There was no correlation with type of JRA onset, course of disease, sex, disease duration, seropositivity for rheumatoid factor, and prior steroid intake. PMID- 8467611 TI - Connection of atopic disease in Japanese patients with juvenile dermatomyositis based on serum IgE levels. AB - Serum IgE levels of 22 patients with juvenile dermatomyositis (JDMS), 44 normal children, and 43 patients with adult dermatomyositis were compared. The geometric mean of serum IgE levels was significantly higher in the juvenile patients when compared with normal children (p < 0.01) and adult patients (p < 0.01). Of the 22 patients with JDMS, 11 (50%) had elevated serum IgE levels accompanied by atopic disease. Dermatomyositis was accompanied by atopic dermatitis (AD) in 9 (41%) of these 22 patients, a high prevalence when compared with reports among the general population. Following the appearance of muscular symptoms in JDMS patients with AD, the ratio of OKT4 to OKT8 cells rose due to a reduction in the percentage of OKT8-positive cells, along with further elevations in serum IgE levels and intractable cutaneous manifestations of dermatomyositis. All this may be a result of an interaction between the immuno-mechanism of this disease and that of AD. We suspect that, in general, children with impaired cell-mediated immunity, presenting with such symptoms as AD, may have a higher tendency for developing JDMS. PMID- 8467612 TI - Estimating lumbar bone mineral density from routine radiographs of the lumbar spine. AB - To evaluate the information content of lateral lumbar films with respect to bone mineral content, we compared reading criteria with values obtained by quantitative computed tomography (CT) of L1 at baseline and after 5 years. The highest correlations with mineral content were found for the criteria "overall assessment of the vertebra", "vertebral bone density versus soft tissue", and "amount of trabeculations". These three reading criteria yielded higher correlations with CT scores in subjects with lower body mass index. Changes in mineral content over the 5-year period could not be read adequately, the average difference representing only a loss of about 10% in the study subjects. We conclude that a rough estimate of bone density can be obtained from lateral radiographs which, in the presence of eventual risk factors for osteoporosis, may serve as an additional indication to timely bone densitometry with methods which allow precise short-term follow-up measurements. PMID- 8467613 TI - Capillaritis: a manifestation of rheumatoid disease. AB - We present seven cases of capillaritis arising in patients with rheumatoid arthritis and suggest that it is primarily related to disease activity and not drugs. In the majority, the rash resolved spontaneously with the use of a topical steroid to treat the symptom of itch. PMID- 8467615 TI - Elevated anticardiolipin antibodies in a patient with vibration-white-finger, valvular heart disease and psoriatic arthritis. AB - We describe a case of irreversible severe vibration-white-finger (VWF) occurring in a male who used a compression-hammer daily at work for a 20-year period. Infra red thermography following either a cold provocation or a vibratory stress was a sensitive objective method of documenting the condition. Persistent elevation of IgG anticardiolipin antibodies (aCL) was found in his serum and may be a marker of endothelial damage associated with either VWF or the patient's coincidental valvular heart disease. PMID- 8467614 TI - The influence of fast and vegetarian diet on parameters of nutritional status in patients with rheumatoid arthritis. AB - Nutritional status was studied over a period of 13 months in 34 patients with rheumatoid arthritis (RA). Seventeen patients fasted for 7-10 days, were then transferred to a gluten-free vegan diet for 3.5 months and finally to a lactovegetarian diet for 9 months. The remaining 17 patients followed a "normal" diet. After one month, the values for body mass index (BMI) and triceps skinfold thickness (TSF) were significantly reduced in the diet group compared with the values at inclusion (p < 0.001), whereas upper arm muscle area (UAMA) was not significantly reduced. Evaluation of the whole study course revealed a significantly lower BMI (p = 0.04) and TSF (p < 0.01) in the diet group compared with the control group. The concentration of insulin-like growth factor 1 (IGF1) was significantly reduced in the diet group after one month compared with the value at inclusion (p = 0.01), but the overall difference between the two groups was not significant. There were no overall significant differences with regard to VAMA, concentration of serum albumin, haemoglobin, ferritin, zinc and copper between the two groups. Thus fast, followed by diet manipulations for one year, had a minor impact on nutritional status in patients with RA. PMID- 8467616 TI - Progressive systemic sclerosis and IgA deficiency in a young man. AB - A 21-year-old man presented with an IgA deficiency and symptoms reminiscent of a systemic lupus erythematosus. After 7 years systemic sclerosis developed involving the lungs, oesophagus, central nervous system and reproductive system. Connective tissue disease and its relationship to IgA deficiency will be discussed. PMID- 8467617 TI - Systemic sclerosis following anti-androgenic treatment for prostatic adenocarcinoma. AB - We describe a male patient who developed systemic sclerosis following orchiectomy, radiotherapy and anti-androgenic treatment for prostatic adenocarcinoma. This case appears interesting as it further supports the possibility of a relationship between neoplasia and systemic sclerosis. The concurrence of scleroderma and iatrogenic hypoandrogenism suggests that hormonal influences may also play a role in the pathogenesis of this connective tissue disorder. PMID- 8467619 TI - Synovial sarcoma manifesting as a single joint flare in rheumatoid arthritis. AB - A 69-year-old female recently diagnosed as suffering from rheumatoid arthritis presented with a general flare-up of disease including a swollen left ankle. Investigation revealed the swelling to be due to a synovial sarcoma. This unusual cause should be considered in all cases of local joint flares in rheumatoid arthritis. PMID- 8467618 TI - Eosinophilic fasciitis in association with chronic vasculitic-like leg ulcerations. AB - Vasculitic lesions are not generally associated with eosinophilic fasciitis. Eosinophilic fasciitis is reported to be a syndrome distinct from progressive systemic sclerosis (PSS). More recent studies, however, note overlapping features in the clinical, pathologic, and laboratory findings of eosinophilic fasciitis and scleroderma. We report a typical presentation of eosinophilic fasciitis that developed vasculitic-like leg ulcerations as seen in scleroderma. PMID- 8467620 TI - Lymphoma developing in a patient with rheumatoid arthritis taking methotrexate. AB - We report one case of non-Hodgkin lymphoma in a patient, with a 30-year history of rheumatoid arthritis, taking low dose methotrexate weekly over a 10-month period. The mild immunosuppression that occurs with methotrexate therapy probably places patients with rheumatoid arthritis at added risk of developing lymphoproliferative diseases, but coincidence cannot be excluded. PMID- 8467621 TI - Evaluation of Abbott TestPack RSV for the diagnosis of respiratory syncytial virus infections. AB - Abbott TestPack RSV, a 20-minute enzyme immunoassay, is available for the rapid diagnosis of respiratory syncytial virus (RSV) infections. We have compared TestPack with a "gold standard" method of virus isolation in traditional tube cultures and shell vials to determine the sensitivity and specificity of this rapid method. Respiratory specimens were collected prospectively from 402 children and assayed by the rapid antigen detection method and isolation in culture. Virus was isolated by inoculation of specimen in a total of eight tubes and 2-3 shell vials. Isolation of RSV was confirmed by characteristic cytopathic effect and immunofluorescence using monoclonal antibodies to RSV. Of the 402 specimens tested, there were only 18 discrepant results (seven TestPack-positive, culture-negative, and 11 TestPack-negative, culture-positive specimens). The sensitivity of TestPack RSV versus culture was 93.6% (162 of 173) and the specificity was 97.0% (222 of 229). Using a very rigorous culture system, we have obtained high values for the sensitivity and specificity of TestPack RSV. This assay is an excellent method for the rapid diagnosis of RSV infections in young children. PMID- 8467622 TI - Species identification and determination of high-level aminoglycoside resistance among enterococci. Comparison study of sterile body fluid isolates, 1985-1991. AB - Enterococcus spp. have become the third most common cause of nosocomial infections. High-level aminoglycoside resistance (HLR), an important clinical concern, has been associated with some species of the enterococci. We evaluated the Vitek and API 20S systems for species identification and the Vitek for the detection of HLR. Enterococci from nosocomial infections (208 strains) at the University of Iowa Hospital (1985-1991) were tested by Vitek, API 20S, and reference methods. The error rate for species identification was 6.7% for the API 20S and 5.8% for the Vitek Gram-positive identification (GPI) cards. Both systems tended to incorrectly identify other enterococcal species as Enterococcus faecium. HLR was found in Enterococcus faecalis and E. faecium isolates only. The highest rates of HLR to streptomycin alone (17.9%) and with gentamicin (13.5%) was observed among E. faecalis strains, and to gentamicin alone (7.3%) was found among E. faecium isolates. No apparent differences in HLR rates were found from year-to-year over the 7-year enterococcus sample interval. Susceptibility errors for Vitek were among the streptomycin tests only. Our results demonstrated acceptable performance by the Vitek cards for enterococcal species identification and the detection of HLR. API 20S also provided an acceptable ability to speciate the enterococci within its data base, however, both systems must be improved by adding other clinical important Enterococcus species. PMID- 8467624 TI - Endovascular infection and septic arthritis caused by Gemella morbillorum. AB - Streptococcus morbillorum was transferred to the genus Gemella in 1988. Infections caused by G. morbillorum are unusual. We report a case of endovascular infection and presumptive septic arthritis caused by G. morbillorum. Previous cases of infection caused by G. morbillorum and G. haemolysans are reviewed. PMID- 8467623 TI - Comparison of oral cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections. AB - This multicenter, randomized, double-blind study was designed to compare the safety and efficacy of cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections. Patients were aged > or = 12 years with acute (< or = 7 days duration), single-site skin or skin-structure infections. The 7- to 10-day treatment regimens were cefpodoxime proxetil (400 mg cefpodoxime) orally with food twice a day with cefaclor-matched placebo (orally, fasting, three times a day); or cefaclor (Ceclor; 500 mg anhydrous equivalent) orally, fasting, three times a day, with cefpodoxime-matched placebo (orally with food twice a day). Clinical progress and cultures were evaluated upon admission to the study; on study days 7-10 and 15-18; and 2-3 weeks after treatment. Cefpodoxime had lower minimum inhibitory concentrations against the majority of Staphylococcus species than did cefaclor. Both treatments were highly effective (99% pathogen eradication and 86% cure rate). These high eradication rates were not unexpected in this study of minor infections in which patients with resistant pathogens were excluded. Cefaclor had a higher failure rate [2 (4%) of 57], than did cefpodoxime [2 (1%) of 139; p not significant]. Most patients in both groups completed treatment as planned: 185 (74%) of 249 cefpodoxime-treated patients and 91 (75%) of 122 cefaclor-treated patients. Both treatments were well tolerated and considered safe and effective in the treatment of skin and skin structure infections. However, the twice-a-day dosing regimen for cefpodoxime proxetil compared with the three-times-a-day regimen for cefaclor may result in better patient compliance. PMID- 8467625 TI - In vitro activity of rifaximin, a topical rifamycin derivative, against Chlamydia trachomatis. AB - Rifaximin is a rifamycin derivative that possesses in vitro activity against a wide range of bacteria. Its antimicrobial spectrum plus poor intestinal absorption have led to consideration of this compound as a topical agent. We evaluated its in vitro activity against clinical and laboratory strains of Chlamydia trachomatis and found that rifaximin exhibits minimum inhibitory concentrations (MICs) at concentrations that would be greatly exceeded in a topical preparation. PMID- 8467627 TI - Impact of intervention on the frequency with which leaky urine specimens are received in the laboratory. AB - Prior to intervention, 4.5% of urine specimens received for culturing in the University of Massachusetts Medical Center clinical microbiology laboratory were noted to have leaked during transport. After an extensive educational program was conducted aimed at alerting physician, nursing, and clerical personnel about the problem, a policy was adopted in which physicians were notified by telephone when the laboratory received leaky specimens. The specimens, however, were processed. Leakage rates dropped to 1.7%. A second round of intervention in which leaky urine specimens were not processed was then implemented. No additional decrease in the rate of receipt of leaky urine specimen was noted (that is, 1.9%). One year later, having adopted a policy of not processing leaky urine specimens, the rate of leaky specimens remained at 1.9%. The clinical microbiology laboratory can effectively intervene regarding problems of specimens that have leaked during transport to the laboratory. PMID- 8467626 TI - Increased resistance to quinolone in Catalonia, Spain. AB - From 1989 to 1991, the level of resistance to ciprofloxacin in our hospital increased from 0.47% to 6.7% in opportunistic Enterobacteriaceae, from 9.9% to 16% in Pseudomonas aeruginosa and from 8.27% to 31.8% in Campylobacter jejuni coli. We also observed an increase in quinolone consumption from 1.1 in 1989 to 1.5 defined daily doses per 1000 inhabitants per day in 1991. PMID- 8467628 TI - Prevalence of enterococcal high-level aminoglycoside resistance in Japan. Comparative detection by three methods. AB - A total of 250 strains of enterococci isolated in Kumamoto University Hospital, Japan, during the period from January to March 1992 were tested for high-level aminoglycoside resistance. Brain-heart infusion (BHI) agar plates supplemented with 1000 micrograms/ml of gentamicin or 2000 micrograms/ml of streptomycin detected 164 (66%) isolates resistant to either gentamicin or streptomycin alone, or both, and consisted of 107 (43%) resistant to gentamicin and 96 (38%) resistant to streptomycin. The Vitek Gram-Positive Susceptibility card (GPS-TA) revealed high correlations with those by agar screens, the results indicating a sensitivity of 100% and 99% to gentamicin and streptomycin, respectively, and 100% specificity to both. Also, the microdilution tests of the National Committee for Clinical Laboratory Standards (NCCLS) showed 100% and 92% sensitivity to gentamicin and streptomycin, respectively, and no false resistance (100% specificity) when compared with the results by agar screens. PMID- 8467629 TI - Molecular technology for hospital epidemiology. AB - Hospital-acquired infections in the United States contribute to approximately 80,000 deaths per year, with an associated cost of > $4 billion. Some of these infections are associated with outbreaks and clusters occurring within the hospital. The hospital infection control team must respond quickly and decisively to recognize and curtail these outbreaks, but their response often depends on critical laboratory data that characterize or "fingerprint" suspected microbial isolates. This presentation summarizes the simple, easily performed tests and the more molecular approaches that a hospital laboratory may take in support of infection control efforts. In addition to phenotypic data, such as biotype and antibiograms, hospitals that elect to incorporate molecular protocols should limit their first experiences to plasmid analysis and plasmid restriction endonuclease profiles. PMID- 8467630 TI - Use of probes and amplification techniques for the diagnosis and prognosis of human immunodeficiency virus (HIV-1) infections. AB - The recent development of nucleic acid amplification methodologies has markedly improved our ability to detect very low levels of specific nucleic acids. Amplification techniques have been combined with product detection systems that are designed for high throughput and are automatable. These developments are drastically changing the face of infectious disease diagnostics and changing the character of prognostic indicators in certain diseases. The polymerase chain reaction (PCR) has been used extensively for diagnosis of human immunodeficiency virus (HIV-1) infections, and recent developments have indicated that quantitative reverse-transcriptase PCR for viral RNA has prognostic value. Self sustained sequence replication amplification for detection of viral RNA appears comparable to plasma culture for diagnosis of pediatric infections. The ligase chain reaction is still in developmental stages, but holds promise for specific purposes. PMID- 8467631 TI - Use of molecular diagnostics in sexually transmitted diseases. Critical assessment. AB - This review describes and assesses the use of molecular assays for the diagnosis of sexually transmitted diseases (STDs). Specifically, data from literature on currently available commercial systems as well as that of imminently to be released assay formats are presented. The focus is on evaluations of two molecular diagnostic techniques--hybridization and amplification for the direct detection of Chlamydia trachomatis and Neisseria gonorrhoeae (gonococci, GC)--the use of urine as a specimen for the diagnosis of these pathogens in humans, a confirmatory probe assay for GC, and finally the description of a hybridization assay for pathogens significant in vaginitis and bacterial vaginosis. Although viral pathogens are a significant part of the STD problem, and molecular techniques have been described for their identification, they are not being discussed here. With the exception of the Virapap DNA hybridization assay for human papillomavirus (Digene Diagnostic, Silver Spring, MD), suitable molecular clinical laboratory assays for viral detection have not been developed for genital samples. PMID- 8467632 TI - A comparison of the API Uriscreen with the Vitek Urine Identification-3 and the leukocyte esterase or nitrite strip as a screening test for bacteriuria. AB - The API Uriscreen is a rapid urine-screening test based on the detection of catalase activity present in somatic cells and in many of the bacteria commonly causing urinary tract infections. Of 487 routine, outpatient urine specimens processed by conventional quantitative culture, API Uriscreen, Vitek UID-3 panel, and a leukocyte esterase-nitrite strip, 142 had no growth. Of 336 urine specimens with > or = 10(3) colony-forming units (CFU)/ml, 79 were considered to be indicative of possible or probable urinary tract infection (Cumitech 2A). The sensitivity and specificity of the API Uriscreen for the detection of bacteriuria at > or = 10(5) CFU/ml were 62% and 85%, those of the leukocyte esterase-nitrite strip was 61% and 82%, those of the Vitek UID-3 panel were 91% and 66%. When bacteriurias were classified into possibly or probably indicative of urinary tract infection, the sensitivity and specificity of the API Uriscreen at > or = 10(5) CFU/ml were 87% and 78%, those of the leukocyte esterase-nitrite were 84% and 76%, those of the Vitek UID-3 were 93% and 55%. In this study, we consider the API Uriscreen did not have significant advantages over the leukocyte esterase nitrite strip. PMID- 8467633 TI - Use of chemiluminescent DNA probes in the rapid detection of oxacillin resistance in clinically isolated strains of Staphylococcus aureus. AB - Chemiluminescent DNA probes (AccuProbe, species specific; and FlashTrack, bacterial generic) were used to determine oxacillin resistance in Staphylococcus aureus. Ribosomal RNA was measured at designated intervals in the presence and absence of antibiotic. A total of 48 (AccuProbe assay) and 24 (FlashTrack) S. aureus isolates with known oxacillin susceptibility patterns were inoculated into Bactec 6A bottles both with and without 4 micrograms/ml oxacillin and incubated at 35 degrees C for 4 h. Aliquots were removed at 0 and 4 h, and pellets of bacteria were obtained via selective centrifugation. Probe assay counts (relative light units, RLUs) were performed. Of 21 oxacillin-resistant S. aureus (ORSA) strains, 20 showed a > 5-fold RLU increase during the incubation period (Accu Probe assay): 25 of 27 oxacillin-susceptible strains demonstrated a < or = 4-fold increase. AccuProbe test sensitivity and specificity were 95% and 92%, respectively. With the generic FlashTrack probe assay, all nine ORSA isolates showed a > or = 4- to 10-fold increase in RLUs, and all 15 oxacillin-susceptible strains showed a < or = 4-fold increase in RLUs during the 4-h incubation. The FlashTrack test sensitivity and specificity were both 100%. Probe assays were completed within 5 h. This study suggests that rapid and reliable determination of oxacillin resistance in S. aureus clinical isolates can be accomplished using commercially available DNA probes. PMID- 8467634 TI - The application of fractal dimension to temporomandibular joint sounds. AB - Researchers have attempted to use mathematical analysis of the sounds produced by symptomatic temporomandibular joints (TMJ) as a diagnostic modality. However, previous studies have generally concluded that such analyses have little diagnostic utility. Previous studies using Fourier transforms and visual inspection were of limited success. This paper reports the results of a preliminary retrospective study using fractal analysis to analyze sounds produced by symptomatic temporomandibular joints previously diagnosed using other clinical modalities as having internal derangements with reducing discs. Multiple mandibular opening and closing cycles were recorded in four subjects. The study revealed that fractal analysis produced a high degree of reproducibility within, and similarity across subjects. The fractual dimension associated with joints having this pathology was found to be 1.266, revealing that fractal analysis shows promise as a noninvasive method for diagnosing interarticular TMJ pathology. PMID- 8467635 TI - A mimetic-based frequency domain technique for automatic generation of EEG reports. AB - This paper describes a novel mimetic technique of using frequency domain approach and digital filters for automatic generation of EEG reports. Digitized EEG data files, transported on a cartridge, have been used for the analysis. The signals are filtered for alpha, beta, theta, and delta bands with digital bandpass filters of fourth-order, cascaded, Butterworth, infinite impulse response (IIR) type. The maximum amplitude, mean frequency, continuity index and degree of asymmetry have been computed for a given EEG frequency band. Finally, searches for the presence of artifacts (eye movement or muscle artifacts) in the EEG records have been made. PMID- 8467636 TI - A computer program in QuickBasic for the selection of tests for the identification of Helicobacter pylori. AB - Reliable microbiological tests are needed for the identification of bacteria. A program has been written in QuickBasic to identify such tests by using a formula that is based on Gyllenberg's Sum of C(i) and Gyllenberg's Rank R(i). A total of 139 papers on a newly isolated bacterium, Helicobacter pylori, was used as data source for the coding of test results into an input file. The program outputs a list that aids in the determination of suitable tests for the identification of H. pylori. These tests chosen by the formula were found to be correctly identified as supported by later publications on the bacterium. PMID- 8467637 TI - Mathematical modeling of time-dependent oxygen transport in rat peripheral nerve. AB - We modeled time-dependent transport of oxygen in peripheral nerve. Simulation began with a steady-state oxygen tension field determined by capillary diameter and length, intercapillary distance, blood-flow velocity, oxygen consumption rate, and arterial oxygen tension. One of these parameters was assumed to change rapidly to new constant value, producing time-varying oxygen tensions. A monoexponential or biexponential function characterized the oxygen tension time variation. Rate constants of the slower exponential ranged from 0.017 sec-1 to 0.46 sec-1, implying minimal time lag in response of peripheral nerve oxygen tensions to alterations in blood flow, arterial blood oxygenation, or metabolic demands. PMID- 8467638 TI - Computer simulation of normal and pathological copper metabolism in man. AB - A digital computer simulation of copper metabolism was used to simulate human copper metabolism. The simulation agrees well with the normal data extant. Wilson's disease (hepatolenticular degeneration) and Menkes' disease (steely-hair syndrome) were simulated. Simulation of the unavailability of accumulated liver copper simulated Wilson's disease if it was assumed that the increased urinary excretion was due to induction of an enzymic mechanism for enhanced excretion. This would be consistent with the genetic defect causing only the sequestering of unavailable copper in the liver. Other genetic defects need not be present. Menkes' disease is also a genetic disease affecting the newborn. It was simulated successfully as a defect in absorption of copper from the gastrointestinal tract. PMID- 8467639 TI - A computer simulation study on the effects of input function measurement noise in tracer kinetic modeling with positron emission tomography (PET). AB - Tracer kinetic modeling with positron emission tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters, i.e. to fit the parameters of certain compartmental models using PTAC and TTAC as the model input and output functions, respectively. However, the estimation usually ignores the measurement noise in plasma tracer activity curves. The accuracy and reliability of the physiological parameters estimated by ignoring such noise are not well understood. In this paper, effects of noise in [18F] 2-fluoro-2-deoxy-D-glucose (FDG) tracer plasma concentration measurements on estimation of local cerebral metabolic rates of glucose (LCMRGlc) with PET is investigated systematically. The PTAC modeling approach used in this paper also provides a realistic means to filter out the noise and to improve the physiological parameter accuracy, which can be potentially used in model-based non-invasive measurements of PTAC. PMID- 8467640 TI - Bioassay from two parabolas. AB - The paper deals with potency ratio estimation of parallel curve analytic dilution assays in case log dose-response relationship could be reasonably described by a parabola. It comprises: (1) testing the adequacy and validity of the quadratic model by the analysis of variance; and (2) estimation of the relative potency of an unknown in relation to a standard preparation, its standard deviation and fiducial limits for its true value. The method is applicable whenever successive doses of an unknown are a constant multiple of a standard in randomized blocks or completely randomized design. The method can be generalized to polynomial models of higher order. PMID- 8467641 TI - Nonparametric estimation of potency ratio for dilution assays. AB - The paper considers the estimation of the potency of an unknown test preparation in relation to a standard in a dilution assay. The method utilizes the Mantel Haenszel one degree of freedom chi-square approach to test consistency of the observed potency ratio with a range of alternative potency ratios. The method is nonparametric as it does not require any distributional assumptions. However, it requires the doses employed to be equally spaced logarithmically. The dose response curve is also required to be monotone over the dose range used. PMID- 8467642 TI - The effect of starting time on dexamethasone suppression test results in horses. AB - This study was conducted to investigate the effect of starting time on dexamethasone suppression test results in horses. Eight adult horses were used throughout the trial. Baseline cortisol levels were established by collecting cortisol levels twice daily, at 8:00 A.M. and 8:00 P.M. for 4 consecutive days. Morning baseline cortisol levels were 46.3 +/- 5.94 ng/ml, and evening baseline cortisol levels were 32.8 +/- 5.59 ng/ml. Although lower, the evening cortisol levels were not statistically different (P = 0.154) from the morning levels. Dexamethasone suppression tests initiated at either 9:00 A.M. or 9:00 P.M. were performed by collected a control blood sample, administering either 0.044 mg/kg dexamethasone or its vehicle intravenously and then collecting additional blood samples at 6, 12, 24, 36, and 48 hr after treatment. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 after a dexamethasone injection given at 9:00 A.M. were 55.6 +/- 3.08, 6.4 +/- 2.05, 0.73 +/- 0.48, 11.0 +/- 5.82, 12.6 +/- 4.30, and 40.5 +/- 5.38 ng/ml respectively. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 hr after a dexamethasone injection given at 9:00 P.M. were 45.0 +/- 6.03, 4.5 +/- 1.28, 0.20 +/- 0.12, 4.5 +/- 2.49, 23.4 +/- 5.88, and 29.5 +/- 6.61 ng/ml respectively. There was no statistical difference in cortisol values between A.M. and P.M. initiated tests at any hour post dexamethasone administration. There was no decrease in cortisol level after administration of dexamethasone vehicle. PMID- 8467643 TI - Lack of effects of indomethacin on estradiol feedback control of luteinizing hormone in ovariectomized ewes. AB - We tested the hypothesis that indomethacin, a potent inhibitor of prostaglandin synthesis, would modify estradiol's effects on tonic and surge concentrations of LH in chronically ovariectomized ewes during the anestrous season. Ewes (n = 21) were assigned randomly to one of four treatments: Vehicle+Blank (n = 5); Indomethacin+Blank (n = 6); Vehicle+Estradiol (n = 5); or Indomethacin+Estradiol (n = 5). On d=0 (hr = 0), ewes began to receive i.m. injections of either indomethacin (4 mg/kg body weight) or corn oil every 8 hr for 9 d. Blood samples were collected every 12 min for 6 hr beginning at -6 hr, +18 hr, and on day 8 (relative to initial injections of indomethacin or vehicle) to assess tonic patterns of secretion of LH. At +24 hr, ewes received blank- or estradiol containing Silastic implants and were bled hourly for 48 hr. On day 9, ewes received 50 micrograms of GnRH i.v. and were bled hourly for 8 hr. Serum samples were assayed for LH. Indomethacin had no effect on the following parameters of LH secretion: 1) mean concentrations (ng/ml; 8.4 +/- .7 vs 8.9 +/- .8; P > .1), 2) pulse frequency/6 hr (4.5 +/- .4 vs 4.1 +/- .4; P > .1) or 3) pulse amplitude (ng/ml; 15.3 +/- 1.1 vs 14.9 +/- 1.2; P > 1). Estradiol elicited a surge of LH which began 18.9 +/- 1.7 hr after implant insertion, reached a mean peak concentration of 95.3 +/- 20.1 ng/ml, and did not differ with respect to indomethacin treatment (P > .1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467644 TI - Basis of norgestomet action as a progestogen in cattle. AB - Norgestomet is the progestational component present in Syncro-Mate-B, which is used to synchronize estrus in cattle. In post-partum cows, luteal phases anticipated to be short following first ovulation are of normal length when cows are pretreated with norgestomet. Because Syncro-Mate-B is used experimentally as a progestogen to affect uterine function, these studies were conducted to investigate how norgestomet acts at the level of the uterus. Receptor binding assays and a sensitive estrogen bioassay in tissue culture were used to address the possibility that some effects of norgestomet might be mediated through interaction of this compound with steroid hormone receptors other than the progesterone receptor (rP). The source of receptors was high-speed cytosol, prepared from bovine uterine endometrium, which was obtained from cyclic cows. Results of single-point and complete competition analyses comparing norgestomet and progesterone indicated that norgestomet competed even more effectively than did progesterone for specific binding of [3H]progesterone to rP. Results of similar studies, which compared the abilities of norgestomet and diethylstilbestrol to compete with [3H]estradiol for binding by uterine endometrial estrogen receptors (rE), provided no evidence for norgestomet competitive binding to rE. In MCF-7 breast cancer cell bioassays, norgestomet showed weak estrogenic activity, but only at concentrations greater than 1 micromolar. Finally, norgestomet did not compete with [3H]triamcinolone acetonide when present in an 100-fold excess, and only competed with [3H]dexamethasone for binding by endometrial glucocorticoid receptors (rG) when present in the micromolar range. We conclude that, at the concentrations used in synchronizing estrus, norgestomet interacts with bovine endometrium as a progestogen and that its biological actions occur through binding of this compound to rP present in target tissues. PMID- 8467645 TI - Determination of the percentage of free cortisol in plasma in the dog by ultrafiltration/dialysis. AB - The current methods for measurement of free cortisol are hampered by methodological drawbacks including large sample requirement, length of the procedure, and overestimation or underestimation of free cortisol. We report a technique combining ultrafiltration and dialysis, which could largely overcome these drawbacks, for measurement of the per cent free cortisol in plasma in the dog. This is a modification of the method of Hammond et al. for the determination of sex steroids in man. We found a good positive correlation (rs = 0.87) with equilibrium dialysis, which is considered the golden standard in free cortisol measurements. The 2.5th and 97.5th percentiles of values of free cortisol measured in plasma of 40 healthy household dogs were 5-20 nmol/l or 5.1-11.7% of the total cortisol concentration. PMID- 8467646 TI - Endogenous growth hormone controls high plasma levels of 3,3',5-triiodothyronine (T3) in growing chickens by decreasing the T3-degrading type III deiodinase activity. AB - The influence of endogenous GH levels on peripheral monodeiodination activity has been investigated in growing chickens at the age of 4 weeks, when they normally show no T3 increase after GH injection. Injection of anti-GH serum decreased plasma T3 and increased plasma T4. Three d and 1 week after hypophysectomy, plasma T3 was also markedly decreased, while T4 was only slightly affected, hepatic 5'D-I activity showed a transient decrease, but 5D-III activity was highly increased, as were the number of hepatic GH receptor sites. Injection of GH in hypophysectomized chickens decreased 5D-III activity and increased plasma T3. GH receptor-deficient dwarf chickens had decreased plasma T3 and increased plasma T4 and hepatic 5'D-I and 5D-III activities compared to their normally growing siblings. GH administration could only affect T3 and 5D-III in the non dwarf siblings, which showed higher basal 5D-III activity compared to the non responsive age-matched chickens of the Hisex strain used in the other experiments. It can be concluded that endogenous GH is an important factor in the control of plasma T3 levels in growing chickens due to its influence on the activity of the T3-degrading type III deiodinase. The effectiveness of exogenous GH administration to acutely increase plasma T3 probably depends on the balance between the injected dose and the endogenous GH concentration, the hepatic GH receptor availability and the hepatic type III deiodinase level. PMID- 8467647 TI - Concentration of bovine placental lactogen in dairy and beef cows across gestation. AB - The concentration of bovine placental lactogen (bPL) was determined in five dairy heifers and five beef cows across gestation. Blood samples were collected beginning at day 45 post insemination and once every two weeks until two d postpartum. Concentrations of bPL in maternal serum ranged from undetectable (< .25 ng/ml) to 2.93 ng/ml and there were no significant differences between dairy and beef animals. Peak concentrations were observed at day 215 of gestation and remained high until just prior to parturition. These results suggest that bPL concentrations follow a pattern similar to that in other species that produce placental lactogen. PMID- 8467648 TI - Effects of season and estradiol on concentrations of histamine within discrete brain regions of ovariectomized ewes. AB - Histamine has been implicated as a neuromodulator of secretion of gonadotropins in several species. Concentrations of histamine were analyzed within discrete brain regions and endocrine tissues to help determine whether this amine has the potential to exert a similar function in ewes expected to have dramatically different serum concentrations of LH. Following collection of blood samples at 12 min intervals for 4-hr, ovariectomized (OVX) and OVX-estradiol treated (OVX-E) ewes were slaughtered during the breeding and anestrous seasons (five animals/group). Concentrations of LH were depressed by treatment with estradiol (E; P < .01), but to a greater extent (P < .05) during the anestrous season compared to the breeding season. Concentrations of histamine in tissues (ng/mg) differed (P < .01) between the breeding and anestrous seasons, in the medial thalamus (39.2 +/- 14.1 vs 109.9 +/- 13.0), posterior pituitary gland (247.6 +/- 50.7 vs 23.0 +/- 9.1) and midbrain tegmentum (10.4 +/- 5.6 vs 50.7 +/- 3.9). Estradiol containing implants decreased (P < .05) concentrations of histamine in the midbrain tegmentum (20.3 +/- 7.1 vs 37.7 +/- 7.8) and posterior pituitary gland (87.3 +/- 24.0 vs 258.2 +2- 67.5) compared to non-estradiol treated controls. Histamine concentrations in the pineal and anterior pituitary glands and brain regions; stalk-median eminence, medial basal hypothalamus, preoptic area, cerebellum, parietal neocortex, were not (P > .05) affected solely by either season or E. An interaction between effects of season and estradiol on concentrations of histamine occurred (P < .05) in the posterior pituitary gland and the preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467649 TI - [Asking about 'nursing and medicine']. PMID- 8467650 TI - [An introduction to Nightingale's nursing]. PMID- 8467653 TI - [A trial in educational development of the general clinical nursing theory]. PMID- 8467652 TI - [The Center for Nursing Research in the University of Michigan]. PMID- 8467654 TI - [Case study reports. 20. (Society for the Study of Scientific Nursing)]. PMID- 8467651 TI - [Building up the science of welfare care]. PMID- 8467655 TI - [What is psychiatry?]. PMID- 8467656 TI - [Beginning course of English medical terminology based on analytical method]. PMID- 8467657 TI - [Searching for logic of children's recognition]. PMID- 8467658 TI - [The world of Hildegard von Bingen]. PMID- 8467659 TI - Tubular cell and matrix changes in renal cystic disease. PMID- 8467660 TI - Potential role of colchicine in the prevention of cast nephropathy from Bence Jones proteins. PMID- 8467661 TI - Urinary excretion of glycosaminoglycans and albumin in experimental diabetes. PMID- 8467662 TI - Response of glomerular filtration rate to protein load in diabetic patients varies according to severity of proteinuria. PMID- 8467663 TI - Terminal parts of the membrane recycling process in rat kidney proximal tubule cells. PMID- 8467664 TI - Tubular proteinuria in diabetic children. A 3-year follow-up study. PMID- 8467665 TI - Microalbuminuria is linked with abnormalities favoring atherosclerosis in type 2 diabetics. PMID- 8467667 TI - Extravasation of plasma proteins into the renal interstitium contributes to the pathophysiology of diabetic nephropathy. PMID- 8467666 TI - Protein charge permselectivity in type 2 and type 1 diabetes. PMID- 8467668 TI - Urinary protein excretion in normal individuals: diurnal changes, influence of orthostasis and relationship to the renin-angiotensin system. PMID- 8467669 TI - Differentiation between renal and postrenal type of hematuria and proteinuria measuring urinary apolipoprotein A1 excretion. PMID- 8467670 TI - Comparison of SDS-PAGE and immunoblotting with polyclonal and monoclonal antihuman albumin sera for the detection of urinary polymers of albumin. PMID- 8467671 TI - An immunoassay method for the determination of rat retinol-binding protein in serum and urine. PMID- 8467673 TI - Renal fibronectin excretion as a marker for renal environmental toxins. PMID- 8467672 TI - Urinary endopeptidase 24.11 as a new marker of proximal tubular injury. Preliminary study in kidney transplant recipients. PMID- 8467674 TI - Hyperoxaluria, enzymuria and nephrolithiasis. PMID- 8467675 TI - Protease inhibitory activity in serum and urine following extracorporeal shock wave lithotripsy. PMID- 8467676 TI - Possible role of altered polyamine metabolism in gentamicin toxicity in OK cells. PMID- 8467677 TI - Immunohistochemical study of epidermal growth factor in the rat kidney after gentamicin-induced tubular injury. PMID- 8467678 TI - Proteinuria and progression of chronic adriamycin nephropathy. PMID- 8467679 TI - Use of renal epithelial cell lines for testing cellular toxicity. PMID- 8467680 TI - The functional effects of contrast media on the isolated perfused rat kidney. PMID- 8467681 TI - Renal effects and nephrotoxicity of contrast media in renal patients. PMID- 8467683 TI - Role of reactive oxygen species in the development of glomerular injury. PMID- 8467682 TI - Contrast media nephrotoxicity: urinary protein and enzyme pattern in patients with or without saline infusion during digital subtracting angiography. PMID- 8467684 TI - Structure-affinity relationship of different drugs at the contraluminal transport system for organic cations in proximal tubules of rat kidneys. PMID- 8467685 TI - Effects of endothelin on coagulation, prostaglandins and hemodynamics. PMID- 8467686 TI - Circadian rhythms of atrial natriuretic peptide and blood pressure are consistently blunted in chronic renal failure. PMID- 8467687 TI - Renal response to colloid volume expansion in patients with solitary kidneys or mesangial glomerulonephritis. PMID- 8467688 TI - The renal catabolic pathways of cytokines. PMID- 8467689 TI - Endosomes degrade insulin. PMID- 8467690 TI - The renal handling of protein 1 (Clara cell protein): effect of age, sex and renal dysfunction. PMID- 8467691 TI - Development of an enzyme-linked immunosorbent assay for protein 1. PMID- 8467692 TI - Increased kidney accumulation of 131I-lysozyme in the uninephrectomized rat. PMID- 8467693 TI - Tubular reabsorption of proteins is a selective process. Evidence from selected nephrotoxicity models. PMID- 8467694 TI - Low-molecular-weight proteins as carriers for renal drug targeting. PMID- 8467695 TI - An unusual case of bovine twin dystocia. PMID- 8467696 TI - Serum chemistry and lipid profiles in neonatal beagle puppies fed homemade milk replacer formulas. AB - Milk replacer formulas based on cow's milk and egg yolks are frequently recommended for use in neonatal puppies. These formulas are lower in protein, kilocalories, calcium, and phosphorus than bitch's milk. In addition, the cholesterol content is greater than bitch's milk. The effect of feeding these formulas on serum chemistry profiles, lipid profiles, and alkaline phosphatase isoenzyme profiles of 5-week-old beagle puppies was studied. Three groups of beagle puppies were fed bitch's milk (control) (n = 18), a homemade milk-egg-oil formula (Formula 1) (n = 18), or a homemade milk-egg-oil formula supplemented with additional calcium and phosphorous (Formula 2) (n = 18). Concentrations of serum urea nitrogen, albumin, and total CO2 were lower (P < 0.05), and concentrations of serum phosphorus, globulins, sodium, chloride, and cholesterol were higher (P < 0.05) in formula-fed puppies than bitch-fed puppies. Serum potassium concentration was lower in the puppies fed Formula 1 than in the control puppies (P < 0.05), and serum potassium concentration in the puppies fed Formula 2 was not significantly different from that in puppies fed Formula 1 or the control puppies. Total triglyceride (TG) and high density lipoprotein2 cholesterol (HDL2) concentrations were similar in all three groups of puppies but the combined high density lipoprotein1 (HDL1) plus low density lipoprotein (LDL) cholesterol fraction was higher (P < 0.05) in the formula-fed puppies and accounted for the majority of the increase in cholesterol. There were no differences (P < 0.05) in total serum alkaline phosphatase (ALP) or bone-derived ALP (BALP) concentrations among the groups, however there was a higher (P < 0.05) serum concentration of liver-derived ALP (LALP) in the Formula 1-fed puppies. Feeding homemade egg and cow's milk-based puppy replacement formulas is not recommended for long term use. PMID- 8467697 TI - Telazol and xylazine anesthesia in sheep. AB - The analgesic and anesthetic effects of Telazol (13.2 mg/kg, IV) and xylazine (0.11 mg/kg, IV)-Telazol (13.2 mg/kg, IV) were evaluated in 6 sheep. Anesthesia was characterized by muscle relaxation and profound analgesia with both regimens, muscle relaxation appeared to be better in sheep receiving xylazine-Telazol. The duration of analgesia was significantly longer in sheep receiving xylazine Telazol (101.7 +/- 26 minutes) than in sheep receiving Telazol alone (41.6 +/- 15 minutes). Changes in heart rate and respiration rate were transient with both regimens. Apnea occurred in 2 sheep immediately after xylazine-Telazol administration, requiring assisted ventilation, but both sheep resumed spontaneous breathing within 2 minutes. Arterial blood pressure decreased significantly at 45 and 60 minutes after xylazine-Telazol injection. Arousal to standing was smooth, but gradual with no significant difference between the two drug regimens. In conclusion, xylazine-Telazol combination produced better muscle relaxation and longer duration of anesthesia than Telazol alone. The adverse effects induced by xylazine-Telazol were similar to that of Telazol. PMID- 8467698 TI - Conservative management of femoral diaphyseal fractures in four foals. AB - Femoral fractures in young horses can occur as a result of severe trauma and generally have a poor prognosis despite treatment. Four young horses with femoral diaphyseal fractures were managed with conservative treatment consisting of prolonged rest, analgesics, hind limb support, and corrective farriery. A favorable outcome in the form of pasture soundness with potential for limited athletic usefulness was obtained in 3 out of the 4 cases. This report supports the use of conservative treatment of selected diaphyseal femoral fractures in young horses. PMID- 8467699 TI - Neuroaxonal dystrophy in a Jack Russell terrier pup resembling human infantile neuroaxonal dystrophy. AB - A 9-week-old Jack Russell terrier with progressive ataxia had histopathological lesions consistent with neuroaxonal dystrophy. Gross observation revealed absence of the septum pellucidum, hypoplasia of the corpus callosum and marked bilateral hydrocephalus. Light microscopy of the CNS revealed extensive axonal swellings principally in the gray matter of the brain stem where the sensory nuclei were most affected. Ultrastructurally, spheroids were identified as axonal terminals and probably dystrophic boutons; they were characterized by accumulations of membrane bound bodies. Clinical and morphological findings are similar to those identified in human infantile neuroaxonal dystrophy (Seitelberger's disease). PMID- 8467700 TI - Clostridium septicum septicemia in a neonatal foal with hemorrhagic enteritis. AB - Clostridium septicum was isolated by anaerobic culture of blood collected from a 3-day-old foal with hemorrhagic enteritis and signs suggestive of septicemia. The foal responded well to treatment with intravenous fluids, antibiotics, plasma, and oral gastrointestinal protectants. One month after apparent complete recovery from the septicemia and hemorrhagic enteritis, the foal was euthanized during an acute episode of colic that was caused by severe, strangulating intestinal adhesions, thought to have formed as a result of peritonitis secondary to the hemorrhagic enteritis. The value of anaerobic culture of blood in foals with signs suggestive of septicemia is emphasized by the case presented here, as is the importance of evaluating the presence and extent of peritoneal inflammation in foals with hemorrhagic enteritis. To our knowledge, Clostridium septicum has not previously been reported to cause septicemia in neonatal foals. PMID- 8467701 TI - Evaluation of ketamine-xylazine in Syrian hamsters. AB - Few parenteral anesthetics are safe and effective in the Syrian hamster. This study evaluated the anesthetic efficacy and potential for tissue damage of ketamine-xylazine (KX). Two dosage levels were administered intraperitoneally. Ketamine at 50 mg/kg combined with 10 mg/kg xylazine did not produce a consistent, reliable level of immobilization or anesthesia. Ketamine at 150 mg/kg combined with 10 mg/kg xylazine administered IP produced an adequate level of anesthesia without tissue damage for most procedures, but supplementation with lidocaine was necessary for peritoneal incision. Careful positioning of male hamsters for IP injection is imperative to prevent inadvertent injection into the testes with subsequent tissue damage. PMID- 8467702 TI - Early-onset leukopenia and severe thrombocytopenia following doxorubicin chemotherapy for tonsillar squamous cell carcinoma in a dog. AB - Doxorubicin is reported to cause myelosuppression, with a white blood cell count nadir occurring between day 7 and day 10. Thrombocytopenia is less severe and occurs between days 3 and 8. This report presents an early onset of leukopenia (day 5) and a severe thrombocytopenia (4000 platelets/microliter) (day 6) associated with doxorubicin administration for treatment of recurrent tonsillar squamous cell carcinoma in a dog. PMID- 8467704 TI - The new veterinary medical teaching hospital at the College of Veterinary Medicine Cornell University. PMID- 8467703 TI - Trichophytobezoar as a cause of transverse colon obstruction in a foal. AB - A 5-week-old belgian colt was examined for colic of 12 hours duration after several episodes of diarrhea. Physical examination revealed signs of abdominal pain, mild dehydration and normal auscultable borborygmi in all abdominal quadrants. Distention of the cecum, large colon and small intestinal was evident on abdominal radiographs. The foal was treated medically as the owners declined surgery. The colt was euthanized because of continued deterioration and failure to respond to medical therapy. Post-mortem exam revealed the presence of a trichophytobezoar obstructing the distal part of the transverse colon. PMID- 8467706 TI - Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection. AB - A cytogenetically detectable deletion, del(10) (q11.2-->q21.2), was observed in a patient with total colonic aganglionosis with small bowel involvement (TCSA), a variant of Hirschsprung disease (HSCR). A similar deletion is present in another TCSA patient (S.M. Huson, personal communication). To reveal cytogenetically undetectable deletions of chromosome 10 in further patients, we developed a strategy for mapping chromosome 10 DNA markers with respect to the observed deletions. To this end, the two chromosome 10 homologs (deleted and normal) were segregated in two distinct somatic cell hybrids obtained after fusion of the patient's fibroblasts with a Chinese hamster ovary cell line (YH21). Hybrid cells containing chromosome 10 were selected for the expression of the gene coding for the beta subunit of the fibronectin receptor (FNRB), which maps to 10p11.2, using a monoclonal antibody against FNRB. Hybrid 185.O contains the deleted chromosome, whereas hybrid 179.Q contains the nondeleted one. Southern blot and PCR analysis of DNA from these two hybrids mapped the markers RBP3H4, RET, D10S15, D10S5, D10S22, and D10S88 inside the deletion and D10S170, CDC2, EGR2, and D10S19 outside the deletion. MEN2A and MEN2B have recently been mapped within the centromeric region closely linked to RBP3 and D10S15 (which are located inside the deletion) and cosegregate with HSCR in at least two different pedigrees. Since HSCR, MEN2A, and MEN2B represent defects of neural crest cell development, we hypothesize that they originate from mutations in different genes clustered in the centromeric region of 10q. PMID- 8467705 TI - Aspergillosis granuloma in the mediastinum of a non-immunocompromised horse. AB - A National Show Horse with a mediastinal granuloma was presented with clinical signs which included fever, nasal discharge and cough. The mediastinal mass was identified radiographically and ultrasonographically. A presumptive diagnosis of aspergillosis was made following isolation of Aspergillus spp. from both transtracheal aspirate and bronchoalveolar lavage fluid samples and agar gel immunodiffusion (AGID) identification of serum antibody to Aspergillus spp. The diagnosis was confirmed by histopathologic examination of the mediastinal mass obtained at necropsy examination. PMID- 8467707 TI - Regional mapping of the Rowett nude gene (RONU) to rat chromosome 10q24-->q32 by localizing linked SYB2 and GH loci. AB - The Rowett nude gene (RONU) has been mapped on rat chromosome (Chr) 10 by linkage analysis using (ACI x F344/N-RONU/RONU)F1 x F344/N-RONU/RONU backcross progeny. The gene order on the chromosome was RR92- (16.1 cM) - RR24 - (17.9 cM) - MYHSE (myosin heavy chain, embryonic) - (1.0 cM) - SYB2 (synaptobrevin 2) - (1.0 cM) - SHBG (sex hormone-binding globulin) - (4.0 cM) - RONU (Rowett nude) - (29.0 cM) - AEP (anion exchange protein), PPY (pancreatic polypeptide) - (3.0 cM) - ACE (angiotensin I converting enzyme), GH (growth hormone). The RONU locus was localized to 10q24-->q32 by fluorescence in situ hybridization of the closely linked SYB2 and loosely linked GH loci on the opposite side. Conserved linkage of homologous loci mapped to rat Chr 10 and mouse Chr 11 supports the hypothesis that the RONU locus is a rat homolog of the mouse nu locus. PMID- 8467709 TI - Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37. AB - UDP glucuronosyltransferases (UGTs) comprise a multigene family of drug metabolizing enzymes. The sub-family of UGTs that conjugate bilirubin and phenolic compounds with glucuronic acid has been termed UGT1A1. In man, UGT1A1 isoforms are encoded by a single gene, UGT1A1. Protein isoforms encoded by UGT1A1 originate by alternative splicing. In the present study, we used the cDNA of UGT1A1*4, a bilirubin-conjugating isoform, to localize the UGT1A1 locus in the human genome. The UGT1A1 gene was assigned by in situ hybridization to chromosome region 2q37. PMID- 8467708 TI - The human gene for the zona pellucida glycoprotein ZP3 and a second polymorphic locus are located on chromosome 7. AB - Southern blot analysis of genomic DNA and gene-cloning experiments have recently shown that the human ZP3 gene is not a single-copy gene. The human genome harbors sequences encoding a protein of 424 amino acids and, in addition, a polymorphic locus with the potential to give rise to a probably nonfunctional polypeptide of 372 residues. In this report it is shown, by screening of a panel of human x hamster hybrid cell lines, that both the ZP3 and ZP3P loci are located on human chromosome 7. PMID- 8467710 TI - Linkage map of 10 polymorphic markers on rat chromosome 2. AB - Analysis of F2 intercross progeny of inbred F344/N x LEW/N rats led to the assignment of 10 polymorphic PCR-typable markers to rat chromosome 2. The markers form a single linkage group covering 47.9 cM with the following order: D2N1R D2N28-FGG (gamma fibrinogen)-PKLR (liver and RBC pyruvate kinase)-ATP1A1 (the alpha-1 polypeptide of Na+/K+ transporting ATPase)-HSD3B (hydroxy-delta-5-steroid dehydrogenase)-D2N2R-D2N91-CAMKI (calmodulin-dependent protein kinase II)-D2N35. All but two of the markers (D2N1R and D2N2R) were detected using specific PCR primers flanking dinucleotide repeats. Sequences with dinucleotide repeats associated with five genes (FGG, PKLR, ATP1A1, HSD3B, and CAMKI) were identified in GenBank, and primers were designed to flank these repeats. The PCR primer pairs for three anonymous markers (D2N28, D2N91, and D2N35) were identified by sequencing cloned LEW/N rat genomic DNA containing (CA)n.(GT)n repeats. D2N1R and D2N2R were identified by PCR amplification of genomic DNA with single, nonspecific 10-base oligonucleotide primers. All of the markers were codominant except for D2N1R, D2N2R, and CAMKI, which only amplified from F344/N homozygous and heterozygous rat DNA. The seven codominant markers were highly polymorphic in 10 other inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUF/N, WBB1/N, WBB2/N, and ACI/N), suggesting that they will be useful for general mapping studies among these strains. Comparative gene mapping analysis indicated that a portion of the mapped region of rat chromosome 2 exhibits synteny conservation with regions of human chromosome 1 and mouse Chromosome 3. PMID- 8467711 TI - Strand-specific FISH reveals orientation of chromosome 18 alphoid DNA. AB - A method is described for making in situ hybridization strand specific. Through the use of a synthetic DNA probe of a repetitive sequence in the centromeric region of chromosome 18, it is shown that the repeats exist in a head-to-tail tandem array. The method should be useful for studies of the molecular organization and mapping of chromosomes. PMID- 8467712 TI - Ribosomal RNA genes are interspersed throughout a heterochromatic chromosome arm in Atlantic salmon. AB - The ribosomal RNA genes (rDNA) have been mapped by fluorescent in situ hybridization (FISH) using four rDNA probes (rDNA/FISH) to Atlantic salmon chromosomes. Signals appeared over the whole heterochromatic chromosome arm displaying the secondary constriction and satellites. The size polymorphism of this sort arm, revealed by C-banding, was confirmed by rDNA/FISH, supporting large interindividual differences in the number of rDNA copies. Conventional techniques for the detection of nucleolar organizer regions are discussed, and their results are compared with those of rDNA/FISH. PMID- 8467713 TI - Comparison of highly repeated DNA sequences in some Lemuridae and taxonomic implications. AB - Highly repeated DNA sequences of Eulemur fulvus mayottensis, E. coronatus, Lemur catta, and Hapalemur griseus griseus have been identified and compared. Sequence analysis of highly repeated DNA fragments isolated from L. catta and Hapalemur showed a high percentage of similarity (nearly 95%), as did fragments isolated from the two very close Eulemur species, whereas comparison of the DNA fragments isolated from the two Eulemur species and the L. catta/Hapalemur group showed a very low percentage (approximately 40%) of identity, as might be expected for distant species. These results confirm our previous data, obtained by Southern blot hybridization techniques on the same species, and strongly support the existence of a common trunk between L. catta and Hapalemur, but different from the leading to the Eulemur species. PMID- 8467714 TI - An X-Y homologous pairing segment in tree shrews (Tupaia). AB - High-resolution early replication banding of tupaia metaphase chromosomes revealed a synchronous early replicating segment in the short-arm telomeric regions of the active and inactive X chromosomes and in the long-arm telomeric region of the Y chromosome. Hybridization with the human-derived pseudoautosomal probe 113F (STIR) showed that this repeat is conserved and specifically localized within these synchronously early replicating segments of the X short arm and the Y long arm of all three tupaia species (Tupaia belangeri, T. chinensis, and T. glis) investigated. Moreover, meiotic studies demonstrated that a synaptonemal complex is formed at one telomeric end of the XY bivalent during the pachytene stage of meiosis in a male T. glis specimen. Thus, apart from the mouse, the tupaias are the first nonprimate mammals for which cytogenetic and molecular evidence is provided that their highly heteromorphic X and Y chromosomes share a conserved homologous segment in the telomeric position, a location that is compatible with pairing and crossing-over in male meiosis. Taken together, these observations strongly, albeit indirectly, suggest that this chromosome segment at the tip of a sex-chromosome arm might behave pseudoautosomally. PMID- 8467715 TI - Refined physical mapping of chromosome 16-specific low-abundance repetitive DNA sequences. AB - Repetitive DNA sequences have been implicated in the origin of several disease phenotypes, including fragile X syndrome, myotonic dystrophy, and spinal bulbar atrophy. In addition, a complex family of chromosome 16-specific low-abundance repetitive (CH16LAR) DNA sequences have been mapped by fluorescence in situ hybridization to regions of chromosome 16 that undergo breakage/rearrangement in acute nonlymphocytic leukemia (ANLL) cells. It has been hypothesized that these repetitive sequences are causally related to the chromosome rearrangements found in ANLL. Here, we further refine the mapping of CH16LAR sequences with respect to the ANLL inversion breakpoints, using a panel of somatic cell hybrids containing 51 different chromosome 16 breakpoints. These studies indicate that CH16LAR sequences at 16p13 are in close proximity to the ANLL short-arm breakpoint region. However, the region containing the highest density of CH16LAR sequences on the long arm appears to be distal to the region where the ANLL long-arm breakpoint has been mapped. These studies further show that CH16LAR sequences map in close proximity to FRA16D and FRA16A. PMID- 8467717 TI - The role of esophageal motility in gastroesophageal reflux disease: technique and clinical results of ambulatory 24-hour mano/-pH-metry. AB - The interplay between esophageal motility and gastroesophageal reflux (GER) was investigated with a new ambulatory system of 24-h monitoring of intraesophageal pressures and pH (MP24). The technique allows for simultaneous digital recordings and off-line data analysis. Both computer-aided and visual analyses were used, and algorithms for intercorrelation of mano- and pH-metry were developed. In a group of normal volunteers the physiological response of esophageal motility on GER was defined. In unselected patients suffering from GER disease, the esophageal motility prior to and during GER events were analyzed. In healthy people, most GER episodes occurred spontaneously and were cleared from the distal esophagus by peristaltic contractions. In GER patients, reflux episodes were often preceded by irregular contractions; during GER, esophageal motility was less often peristaltic compared with controls. Therefore, we conclude that MP24 gives relevant information in GER disease which might help in selecting patients for medical or surgical therapy. PMID- 8467716 TI - Clinical use of ambulatory 24-hour esophageal motility monitoring in patients with primary esophageal motor disorders. AB - The development of miniaturized electronic pressure transducers and portable digital data recorders with large storage capacity has made ambulatory monitoring of esophageal motor function over an entire circadian cycle possible. Broad clinical application of this new technology in a large number of asymptomatic normal volunteers and patients with symptoms suggestive of a primary esophageal motor disorder provides new insights into esophageal motor function under a variety of physiologic conditions in health and disease. These studies suggest that ambulatory esophageal motility monitoring allows for a more precise classification of esophageal motor disorders than standard manometry and can identify abnormal esophageal motor patterns associated with nonobstructive dysphagia or noncardiac chest pain. Ambulatory esophageal motility monitoring performed in combination with pH monitoring is currently the most physiologic way to assess esophageal function and has potential to improve diagnosis and management of patients with esophageal motor disorders. Ambulatory 24-h esophageal motility monitoring should become the gold standard for assessing motor function of the esophageal body. PMID- 8467718 TI - pH monitoring: the gold standard in detection of gastrointestinal reflux disease? AB - Gastroesophageal reflux disease (GERD) is one of the most frequent benign diseases of the gastrointestinal tract and in some cases the diagnosis may be very difficult. There are many diagnostic procedures but none of them could prove or definitely exclude the disease. The 24-h pH-monitoring is the "gold standard" for detection of gastroesophageal reflux and in many patients the reflux correlates with the GERD. The evaluation of a diagnostic method has to be done in a similar manner to the evaluation of therapeutic study (phase 1 to phase 4). For the definition of the "gold standard" for detection of a special diagnosis (e.g., the gastresophageal reflux disease), the results of phase 3 studies for different methods had to be compared. The method with the best values for sensitivity and specificity is yet to be discovered. Until now, pH monitoring has been the gold standard for the diagnosis of GERD. However, there are many problems connected with using this method in clinical practice. PMID- 8467719 TI - pH monitoring: is it the gold standard for the detection of gastroesophageal reflux disease? AB - Ambulatory, long term (24-h) intraluminal esophageal pH monitoring is the "gold standard" for detection and quantification of gastroesophageal reflux. Is it, however, the "gold standard" for the diagnosis of gastroesophageal reflux disease (GERD)? The answer depends in part on how GERD is defined. Is it to be defined on the basis of symptoms, inflammatory changes in the esophageal mucosa, extent of the exposure of the esophagus to acid or some combination of these factors? Since the correlation between acid exposure of the esophageal mucosa and either symptoms or histologic changes is poor at best, it seems there must be factors in addition to acid exposure that determine the severity of symptoms and histologic damage. One such is the resistance of the individual patient's mucosa to injury by acid exposure. In view of the above, it is not surprising that no specific value for acid exposure of the esophagus can be equated with the diagnosis of GERD. The addition of the symptom index, the frequency with which symptoms coincide with reflux episodes, has done little to increase the sensitivity and specificity of pH recording in the diagnosis of GERD. Another variable only occasionally considered is the day to day variation in the frequency and duration of acid reflux. Finally, intraesophageal pH recording measures only the intensity of acid exposure but we have no clinical measure of mucosa resistance to acid induced injury, the other factor contributing to the pathogenesis of GERD. PMID- 8467722 TI - Swallowing therapy in patients with neurological disorders causing cricopharyngeal dysfunction. AB - The results of swallowing therapy in 28 patients with neurological disorders causing cricopharyngeal (CP) dysfunction are reported. Variables described include the type of swallowing disorder, type and degree of aspiration, and therapeutic strategies. Patients were monitored by cineradiography before, during, and after therapy. Success of therapy was defined by progress in type, ease and safety of feeding, and range of diet. As an example, a case of an unusually severe disorder of a CP opening subsequent to brainstem meningoencephalitis is described. The bedside clinical evaluation, otolaryngologic findings, and radiographic studies helped determine an individualized program of swallowing therapy. Therapy goals, direct and indirect therapeutic strategies, and the treatment outcome are presented. Ninety percent of patients with CP dysfunction improved with swallowing therapy, 65% by objective and 25% by subjective criteria. We conclude that in neurological patients with CP, dysfunction can effectively be treated with swallowing therapy and that surgical approaches to CP dysfunction should be deferred pending the outcome of conservative management. PMID- 8467723 TI - Swallowing therapy with neurologic patients: results of direct and indirect therapy methods in 66 patients suffering from neurological disorders. AB - The results of direct and indirect therapy methods applied to 66 patients suffering from neurological disorders are presented. Variables considered were age, time since lesion, localization of central nervous system lesion, type of swallowing disorder (defined according to swallowing phase, type of aspiration and degree of aspiration), cognitive deficits (memory, planning/problem-solving, and attention deficits), and duration of therapy. Success of therapy was defined by progress in type, ease, and safety of feeding and by range of diet. Therapeutic outcome was correlated with the above-listed variables. The findings suggest that swallowing therapy is effective for patients with neurological disorders. PMID- 8467720 TI - Medical treatment of esophageal motility disorders. AB - Swallowing is a complex mechanism that is based on the coordinated interplay of tongue, pharynx, and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain, or regurgitation. The major esophageal motility disorders include achalasia, diffuse esophageal spasm, hypercontractile esophagus ("nutcracker esophagus"), and hypocontractile esophagus ("scleroderma esophagus"). Other esophageal diseases such as hypopharyngeal (Zenker's) diverticula or gastroesophageal reflux disease also may be sequelae of primary esophageal motility disorder. Finally, a substantial group of patients referred for evaluation of possible esophageal motor disorders have milder degrees of dysmotility--referred to as nonspecific esophageal motor disorder--that are of unclear clinical significance. Medical treatment of esophageal motility disorders involves the uses of agents that either reduce (anti-cholinergic agents, nitrates, calcium antagonists) or enhance (prokinetic agents) esophageal contractility. Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment is often disappointing. From clinical and epidemiological studies there is some evidence for a "psychological" component in the pathogenesis or perception of esophageal symptoms. Further understanding of esophageal pathophysiology, as well as development of new receptor selective drugs, might increase our chances of successful treatment of esophageal motility disorders. PMID- 8467721 TI - The surgical management of motility disorders. AB - Surgical treatment is either the therapy of choice or a facultative procedure in various types of esophageal motility disorders. In achalasia, cardiomyotomy, frequently combined with fundoplasty, achieves good or excellent results in > 80% of cases, and is, therefore, advised in cases when pneumostatic dilatation fails. Diverticulectomy and myotomy of the upper or lower esophageal sphincter are proven procedures to treat cervical and epiphrenic diverticula, leading to good/excellent results or at least an improvement in more than 95%. If, exceptionally, parabronchial diverticula require therapy, they should be excised transthoracically. Cervical myotomy is indicated in cases of cervical achalasia, when sufficient pharyngeal propulsion is preserved. In systemic diseases like scleroderma reflux induced complications may require surgical intervention in medically intractable cases. In these rather few cases, subtotal gastrectomy with a Roux-en-Y anastomosis is advised. In patients suffering from diffuse esophageal spasm or symptomatic "nutcracker" esophagus, extended esophageal myotomy can relieve symptoms. If a clear diagnosis is provided, about 75% of patients will have an improvement of symptoms. PMID- 8467724 TI - Drug-induced dysphagia. AB - Dysphagia describes the disability or problems in swallowing a wet or dry bolus properly and is normally associated with an impaired transport of the bolus. Dysphagia can be accompanied by a pain sensation in the chest mostly caused by impaction of the food bolus in the esophagus. Odynophagia describes only the status of painful swallowing without an impairment of the swallow and transport function. Drug-induced dysphagia can be caused in two different ways. First as a normal drug side effect of the pharmacological action of the drug or as a complication of the therapeutic action of the drug. The normal drug side effect is most likely in drugs that affect smooth or striated muscle function or the sensitivity of the mucosa. The drug effect on smooth muscle function that causes dysphagia can be inhibitory or excitatory. Dysphagia is a common clinical symptom in patients with reduced perception of the pharyngeal mucosa which leads to an subjective impairment of swallowing. Dysphagia caused by a complication of the therapeutic action of a drug includes viral or fungal esophagitis in patients treated with immunosuppressive drugs or cancer therapeutic agents, or antibiotics and immunological reactions to certain drugs such as erythema exsudativa multiforme or Stevens-Johnson syndrome. Second, drug-induced dysphagia can be due to medication-induced esophageal injury (MIEI). In most cases this mucosal injury appears to be the direct result of prolonged contact of a potentially caustic drug with the esophageal mucosa. This form of medication-induced esophagitis is most likely to be found in elderly patients and patients with esophageal motility disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467726 TI - Art and science of history taking in the patient with difficulty swallowing. AB - History taking is the first step in the evaluation of a patient. An analysis of the information obtained provides the basis for the choice and order of diagnostic tests. In addition, it provides the clinician with the necessary information to determine the relevance of "abnormal tests" to the patient's problem. Dysphagia is a reliable symptom that indicates an abnormality in the swallowing mechanism. The history should contain a detailed description of the symptoms associated with dysphagia from the onset. Especially relevant are questions to determine if dysphagia is experienced every day or intermittently, with solid food or liquids or both, as well as presence and timing of associated symptoms such as, choking, coughing and regurgitation, changes in speech, heartburn and chest pain. It is clinically useful to divide swallowing into three phases: oral, pharyngeal and esophageal. Oral dysphagia is usually due to a neurologic disorder, decreased salivary flow or painful oropharyngeal lesions. Pharyngeal dysphagia is most frequently caused by neuromuscular disorders and less frequently by a Zenker's diverticulum, neoplasm or a mucosal web. Esophageal dysphagia is caused by a structural narrowing, such as produced by a peptic stricture, neoplasm or a Schatzki's ring or by a primary motility abnormality, such as achalasia or diffuse esophageal spasm or by motility abnormalities produced by inflammation caused by gastroesophageal reflux, medication-induced esophageal ulceration or infectious esophagitis. PMID- 8467725 TI - Wylie J. Dodds, M.D.: a memorial "going funded". PMID- 8467727 TI - Coordination of peristalsis in pharynx and esophagus. AB - When a swallowed liquid bolus is followed from mouth to stomach in man by contrast studies or manometry, it traverses its course without hesitation even though the bolus is propelled by striated muscle contraction in the first part of its journey and smooth muscle in the latter part. The striated muscle is innervated by excitatory cholinergic nicotinic cranial nerves whereas the smooth muscle of the esophagus is innervated by the enteric nervous system (ENS) through excitatory and inhibitory nerves. These differences can be demonstrated by observing the inhibitory effects of curare and atropine, the first blocking nicotinic receptors and the second muscarinic receptors. Early students of esophageal motility recognized that peristalsis could be initiated in two ways. The first is initiated by a swallow and is called primary peristalsis and the second called secondary peristalsis is initiated by distension of the esophagus. It was proposed that primary peristalsis was initiated by a single sensory input activated by the bolus entering the pharynx which in turn activated a motor program in the brain stem. Secondary peristalsis was believed to be stimulated by multiple afferent impulses arriving from the esophagus as the bolus passed down the esophagus. More recent studies using manometric techniques have suggested that the only difference between primary and secondary peristalsis is the afferent stimuli and the effector mechanism is the same. Subsequent studies of carefully timed, paired swallows, transection of vagus nerves and esophagus, and single nerve recordings suggest that the answer lies between the two extremes noted above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467729 TI - Commentary on the determination of the evaluation of dysphagia. PMID- 8467730 TI - Dysphagia in dermatologic disease. AB - Disorders of the oral cavity, pharynx, and esophagus may be found in some dermatologic diseases. The connective tissue diseases especially may be accompanied by dysphagia. Furthermore, some rare inflammatory and bullous dermatologic diseases can lead to esophageal disorders. Finally, some infectious and malignant diseases occurring in human immunodeficiency virus (HIV)-infected patients cause dysphagia (Table 1). The following discussion presents a comprehensive review of these diseases and their typical esophageal dysfunction. PMID- 8467728 TI - The gastroenterologist's approach to dysphagia. AB - In the gastroenterological diagnostic armamentarium, dysphagia is considered as an important symptom for diseases of the esophagus. Concerning the history of illness, symptoms such as retrosternal pain and heartburn are often associated with gastroesophageal reflux disease. Morphological changes of the mucosa can be diagnosed by flexible endoscopy and radiographic examinations. Investigation with 24-h pH monitoring, manometry, and pharmacological tests is necessary for the diagnosis of functional disorders. Additionally, dysphagia can be associated with multiple internal diseases, including muscular diseases such as dermatomyositis, progressive systemic sclerosis, as well as lupus erythematosus. Difficulties in swallowing associated with hypo- and hyperthyroidism can also be interpreted as muscular lesions. Metabolic disorders such as alcoholism, and diabetes mellitus can be the cause of dysphagia. Increasing importance in the differential diagnosis of dysphagia is attached to infections of the upper GI tract. Especially in immunocompromised patients, infections of Candida albicans, mycobacterias, herpes, varicella zoster, and cytomegaloviruses can produce dysphagia and odynophagia. The differential diagnosis of the "angina-like chest pain" has to differentiate between cardiac disease and a noncardiac genesis. Therefore, besides the cardiac diagnostic investigation, endoscopy, radiography, and manometry are often indicated. PMID- 8467731 TI - The value of endoscopy and endosonography in the diagnosis of the dysphagic patient. AB - The value of endoscopy in dysphagia is limited in the diagnosis of motility disorders and small structures, webs, and hiatal hernias. Endoscopy is of special use for the clarification of an organic cause of dysphagia. Intraluminal tumors can be seen and in a high percentage of cases be definitely diagnosed by taking biopsies; a malignant degeneration in Barrett's esophagus is detectable by endoscopy in 89.1% of cases. Gastroesophageal reflux disease can be diagnosed on endoscopy as it leads to an endoscopically visible inflammatory reaction; however, normal findings on endoscopy cannot exclude reflux disease. Endoscopy is the method of choice in the diagnosis of nonreflux esophagitis, especially Candida and viral esophagitis. A further advantage of endoscopy is the fact that a microscopic diagnosis can be obtained and endoscopic treatment can be performed simultaneously. Submucosal or extramural lesions can be missed by endoscopy. Endosonography, the combination of endoscopy and ultrasonography (EUS) yields additional information in diagnosing submucosal and extramural lesions of the esophagus which is missed by other imaging procedures. One of the main advantages of EUS is the detection of small and submucosal lesions. The most important indication is the local staging of esophageal carcinomas; the accuracy of endosonography in determining the depth of infiltration ranges between 79% and 92%. The detection of paraesophageal lymph nodes is successful in 60%-82%, although EUS cannot differentiate benign from malignant lymph nodes. Submucosal tumors can be visualized by endosonography and their size, echopattern, and the layers of origin can be determined with high accuracy. Further indications for EUS are the exclusion of focal lesions in achalasia or peptic strictures. PMID- 8467732 TI - The place of esophageal manometry in the diagnosis of dysphagia. AB - Esophageal manometry allows to quantify intraluminal pressure changes as the basis of normal or abnormal esophageal motility. It is a complementary diagnostic procedure which should only be performed after endoscopic and fluoroscopic examinations and may be helpful in the detection of various motility disorders like diffuse esophageal spasm, nutcracker esophagus and vigorous achalasia. Manometry is recommendable for therapy control after medical and surgical therapy, and mandatory prior to surgical reflux therapy. PMID- 8467733 TI - [Intra-individual variations in triglyceride and total cholesterol levels in serum in mixed hyperlipidemia]. AB - Swings in serum concentrations of total cholesterol and triglycerides were assessed retrospectively in 12 of 60 patients with mixed hyperlipidaemia (ten men, two women; mean age 44 [38-55] years). A second disease as a cause of the hyperlipidaemia had been excluded. Despite clinical stability and unchanged drug therapy the fasting values of triglycerides, measured enzymatically, in a minimum of four different samples (over several months) differed by more than 5 mmol/l, a mean of 16.6 (5-41.9) mmol/l. The lowest values were 2.7 (1.3-7.5) mmol/l, the highest 17.9 (6.4-44.6) mmol/l. Total cholesterol concentrations varied around 5.5 (1.6-31.7) mmol/l, minimal values 5.7 (4.2-8.9) mmol/l, maximal ones 12.0 (6.9-37.4) mmol/l. Six of the twelve patients consumed more than 60 g alcohol daily. The cause of the marked variations between individual samples is uncertain. Marked swings in triglyceride and total cholesterol concentrations are likely in mixed hyperlipidaemia. It is, therefore, essential to measure these concentrations repeatedly to assess correctly the diagnosis and treatment. PMID- 8467734 TI - [Acute plasma cell leukemia. Clinical course during high-dose melphalan therapy]. AB - A 29-year-old woman, with a slightly elevated temperature for 3 weeks, increasing dyspnoea at rest, markedly reduced general condition and in heart failure, was found to have a leucocytosis of 100,000/microliters, anaemia (haemoglobin 6.3 g/dl) and thrombocytopenia (41,000/microliters). There were 62% plasma cells in the blood smear. Immunoelectrophoresis of serum and urine revealed kappa-light chains and immunocytology demonstrated IgG-kappa. There was no radiological evidence of osteolysis, while ultrasound examination showed multiple abdominal lymphomas and marked hepatosplenomegaly. Bone marrow smear showed a 90% infiltration of plasma cells. High-dosage melphalan treatment (single intravenous injection of 140 mg/m2) resulted in complete remission after myelodepression over several weeks. Two extramedullary recurrences 5 and 12 months after the diagnosis had been made were successfully treated with high-dosage melphalan, but it was associated with severe and long-lasting myelodepression. Septicaemia with renal and hepatic failure developed and the patient died 6 weeks after the third course of high-dosage melphalan, 14 months after the diagnosis. PMID- 8467735 TI - [Mediastinal chloroma with right heart involvement. Unusual cause of a superior vena cava syndrome]. AB - For four months a 28-year-old man had been suffering from a sensation of pressure in his head when lying down, swelling of the face, exertional dyspnoea and weight gain of 9 kg. Biochemical tests and chest radiograph were unremarkable. Echocardiography revealed a 3 x 5 cm mass in the right atrium, extending into the superior vena cava whose lumen was narrowed to a few millimetres. Computed tomography and magnetic resonance imaging were suggestive of a malignant tumour. Bone marrow biopsy as well as transvascular and mediastinoscopically obtained biopsies failed to provide a pathological diagnosis. Exploratory thoracotomy uncovered a nonresectable chloroma surrounding both venae cavae. It had penetrated into the right and left atria, as well as the pulmonary veins. A Gore tex bypass was placed between the innominate vein and right atrial appendage. The tumour was identified as a local manifestation of acute myeloid leukaemia. Treatment with idarubicin (12 mg/m2 daily for 3 days) and adriamycin (1.5 mg/m2 daily for 4 days) followed by radiotherapy with 35 Gy achieved partial remission and 15 months after onset of treatment the patient is in a good general condition. PMID- 8467736 TI - [Symptoms and diagnosis of Lyme borreliosis]. PMID- 8467739 TI - [Gastric lymphoma following chromium or nickel exposure?]. PMID- 8467738 TI - [What are the facts in the treatment of diabetic nephropathy?]. PMID- 8467737 TI - [McLeod syndrome]. PMID- 8467740 TI - [Calcium replacement in hemotherapy]. PMID- 8467741 TI - [Intramuscular injection of vaccines]. PMID- 8467742 TI - [Differential diagnosis of hypereosinophilia syndrome]. PMID- 8467743 TI - [Mercury sensitization in amalgam fillings. Assessment from a dermatologic viewpoint]. AB - Epicutaneous tests were performed on 88 patients (27 men, 61 women; mean age 36.8 [18-68] years) thought to have an allergy against amalgam or mercury. In addition their oral mucosa was assessed clinically. The epicutaneous test was positive for mercury sensitization in seven patients, five of them reporting oral mucosa symptoms. Such symptoms also occurred, although less frequently, in non sensitized patients (30 of 81). In three sensitized patients there was evidence of perioral dermatitis which in two of them cleared up after removal of the amalgam fillings. Two further patients had no further complaints, such as burning sensation on the oral mucosa, recurrent aphthous ulcers or gingivitis, after removal of amalgam fillings. In one patient each peroral eczema and diarrhoea aggravated after amalgam fillings had been taken out. These observations indicate that responses to mercury allergy are not uniform and show considerable individual variations. There is no reason to advise against or prohibit the use of amalgam fillings. Their substitutions by other materials may well bring about other types of allergy. PMID- 8467745 TI - [Rothmund-Thomson syndrome]. AB - One year after a normal birth a girl developed large, flat and net-like telangiectasias and erythema with hyper- and depigmentation (poikiloderma), at first in the face and later on the limbs, sparing the trunk. There was increased light sensitivity of the affected areas. At 3 years and 8 months of age her height was diminished (3rd percentile; height 104 cm, weight 15 kg) and she had a deep nasal root and bradydactylia. These cutaneous and extracutaneous abnormalities correspond to the spectrum of Rothmund-Thomson syndrome which has a wide clinical heterogeneity. The family history for this condition was negative. PMID- 8467744 TI - [Severe hemoptysis in pulmonary vasculitis]. AB - A 27-year-old man, in good health but a moderate smoker, suddenly had two episodes of haemoptysis. Routine clinical examination was unremarkable. Erythrocyte sedimentation rate was increased to 34 mm/h. The chest radiography showed ill-defined, contrast-poor infiltrations bilaterally, as well as left hilar enlargement. Lung scintigraphy and pulmonary arteriogram suggested pulmonary embolism, possible from a "pelvic vein spur", i.e. an intimal proliferation due to crossing of the common iliac artery over the pelvic vein. He was placed on oral anticoagulants. Three months later he had another severe haemoptysis, providing the indication for an exploratory thoracotomy. This revealed the left pulmonary artery wall to have inflammatory changes with aneurysmal dilatation. The aneurysm was plicated. Histological examination demonstrated chronic vasculitis as seen in Behcet's syndrome, a diagnosis confirmed by the findings of ulcers of the oral mucosa and the presence of HLA B5 allo-antigens. Immunosuppressive treatment was given with prednisone (1 mg/kg), azathioprine (2.5 mg/kg) and ciclosporin (5 mg/kg). Over the next 12 months there has been only one further haemoptysis. PMID- 8467746 TI - [Therapy of Lyme borreliosis]. PMID- 8467747 TI - [Circadian incidence of cardiovascular incidents and hypertension upon awakening]. PMID- 8467749 TI - [Thrombocytopenia following Varicella zoster infection]. PMID- 8467748 TI - [Azathioprine in Crohn disease]. PMID- 8467750 TI - [Penicillin-resistant pneumococci in the German Federal Republic]. PMID- 8467751 TI - [Prognosis of legasthenia]. PMID- 8467752 TI - [Analgetic irradiation of degenerative-inflammatory skeletal diseases. Benefits and risks]. AB - Between 1980 and 1991, ionizing radiation was applied for analgesic purposes to 181 patients (97 men, 84 women, mean age 54 [29-81] years) with degenerative inflammatory skeletal disease. The long-term effects were evaluated by questionnaire. Radiation of 2.5 to 6.0 Gy achieved lasting pain relief in 21 of 30 patients (70%) with arthritis of the shoulder or humeroscapular periarthritis, 15 of 21 (71%) with arthritis of the hip, in 12 of 15 (80%) with heel spurs or Achilles tendon bursitis and 10 of 11 (91%) with epicondylitis. Pain relief lasted for longer than two years in 41 of the 77 patients (53%). There were no side effects at the stated dosage. According to dose measurements the theoretical risk of malignant tumour induction is 20-40/million radiated patients and thus four orders of magnitude below the spontaneous malignant tumour incidence rate. The genetic risk is even lower. Ionizing radiation of degenerative-inflammatory diseases is thus an effective form of treatment with few side effects. PMID- 8467753 TI - [Stent implantation in solitary aneurysm of the common iliac artery]. AB - A 56-year-old man had intermittent claudication in the right leg for 11 months, gradually worsening of late. Digital subtraction angiography demonstrated an aneurysm, 8 x 2.5 cm, of the right common iliac artery and 70% stenosis of the right external iliac artery. As the patient refused full surgical intervention the aneurysm was treated by the insertion of two exactly adjoining wall stents (diameter 9 mm, length 7 cm), and the arterial stenosis was balloon-dilated. One month after stent implantation the aneurysm had thrombosed outside of the stent and the stent lumen was being perfused normally. 6 months later the local findings were identically. The patient remained symptom-free. --The case illustrates that management of circumscribed aneurysms by stent implantation could well be an alternative to surgical treatment, as long as the stent can prevent enlargement and rupture of the aneurysm. PMID- 8467754 TI - [Endobracyesophagus. Pathogenesis, epidemiology and malignant degeneration]. PMID- 8467755 TI - [Post-traumatic splenectomy]. PMID- 8467756 TI - ["Tumorous" overgrown gastrostomy tube]. PMID- 8467757 TI - Nutrition and lung structure and function. PMID- 8467758 TI - Effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema in the rat. AB - The effect of a synthetic leukocyte elastase inhibitor on thrombin-induced pulmonary edema was studied in rats. The chloromethylketone human neutrophil elastase inhibitor, ICI 200,355, blunted rat leukocyte elastase activity in rat lung tissue. Administration of thrombin produced a significant increase (p < .01) in lung weight. The wet weight to dry weight ratio (WW/DW) and relative water contents were also significantly elevated (p < .01). Pretreatment with ICI 200,355 (200 micrograms/kg h-1) resulted in significant reductions (p < .05) in lung weight and a tendency to decrease WW/DW and water content compared with animals given thrombin alone. It is possible that the elastase inhibitor effectively reduced the rate of thrombin-induced pulmonary edema by attenuation of increased vascular permeability. PMID- 8467759 TI - Lung antioxidant enzymes and cardiopulmonary responses in young rats exposed to hyperoxia and treated intratracheally with PEG catalase and superoxide dismutase. AB - The 27-day-old rat exposed to 100% oxygen (O2) for 8 days will have predictable lung vascular and parenchymal changes at 60 days of age. Using this model, the goals of this study are (1) to measure the lung antioxidant enzyme activities serially following intratracheal PEG antioxidant therapy during the 8-day O2 exposure; and (2) to assess chronic cardiopulmonary changes in the O2-exposed rats treated with PEG-CAT and/or PEG-CuZn SOD given intraperitoneally (IP) and/or intratracheally (IT). The study encompassed 202 male rats exposed to room air or oxygen. CuZn SOD doses were 300 U IT and 2000 U IP. The CAT dose was 500 or 4000 U IT and 10,000 U IP. At 60 days of age, the right ventricular systolic pressure (RVP), RV weight, % acinar wall arterial thickness, and parenchymal air space were significantly increased in O2-exposed rats compared to RA rats. The RVP, RV weight, and parenchymal changes were prevented by daily IT PEG-CAT 4000 U + CuZn SOD 300 U but the increased small artery muscularization was not. Three hours after the initial dose of IT PEG-CAT 4000 U, lung CAT activity was more than doubled and remained constant throughout the 8-day daily treatment course. This dose of CAT depressed the induction response to O2 of CuZn and MnSOD. It is concluded that daily intratracheal administration of PEG-CAT 4000 U + CuZn SOD 300 U can significantly ameliorate some of the chronic parenchymal and vascular lung O2 toxic changes. However, it appears that high-dose exogenous PEG-CAT suppresses the endogenous enzyme induction to hyperoxia of both CuZn and Mn-SOD. PMID- 8467760 TI - Pulmonary epithelial cell proliferation in primary culture of alveolar type II cells. AB - A small subpopulation of pulmonary epithelial cells (PE) proliferates in low density primary culture of alveolar type II cells and forms colonies of cells that could be passaged for several generations and that in some respects maintain a differentiated phenotype of the alveolar type II cells. At this time it is not known if these cells are some form of progenitor epithelial cells or type II cells that are not fully differentiated in vitro. The proliferation of the PE cells was dependent on serum, alveolar macrophage-conditioned medium, and insulin being included in the culture medium. Under these conditions, approximately 0.5 1.0% of the seeded cells that adhered to the culture dishes were capable of forming colonies. Efficiency of colony formation increased to 5-10% in subsequent passages. PE cells maintained a high level (> 40%) of saturated phosphatidylcholine (PC) as a percentage of total PC throughout the culture period (> 28 days). However, the saturated PC content was not constant throughout the long-term culture period and the subsequent passages (41.3% at 29 days and 37.3% in the 3rd passage). These cells also contained numerous lamellar bodies and were able to bind the Maclura pomifera lectin. PE cells also expressed cytokeratin No. 19, as well as alkaline phosphatase activity, both possible markers for differentiated type II cells. However, PE cell synthesized low levels of Pg (approximately 2%), were squamous, and tended to form multiple strata, unlike the cuboidal type II cells in vivo. The cells did not exhibit immunocytochemically demonstrable surfactant-associated protein A (SP-A). Additional factors and culture requirements may be necessary for complete maturation of cultured PE cells. This was demonstrated by culturing PE cells on EHS matrix. Aggregates of cells surrounding a central lumen were formed after a few hours in culture and were maintained for 20 days. The cells contained lamellar bodies and some intercellular junctions. PE cells can be regarded as a highly selected subpopulation of pulmonary epithelial cells that concomitantly maintain proliferation and aspects of differentiated alveolar type II cells in long-term culture. PMID- 8467761 TI - Pulmonary air-space enlargement induced by intratracheal instillment of hyaluronidase and concomitant exposure to 60% oxygen. AB - Although emphysema is generally characterized by damage to pulmonary elastic fibers, the causes of such injury appear to be complex and are not entirely explained by a singular imbalance between elastases and their inhibitors. Other factors could compromise elastic fiber integrity. To test the validity of this argument, hamsters were instilled intratracheally with a nonelastolytic enzyme, hyaluronidase (which reduces lung hexuronic acid content by 21% after 24 h), then exposed to an otherwise nontoxic concentration of oxygen (60%) for 4 days. Additional groups were given (1) hyaluronidase and room air, (2) saline and 60% oxygen, and (3) saline and room air. Treatment with both hyaluronidase and 60% oxygen resulted in a significant increase in air-space enlargement at 4 days (67.1 vs. 57.9 microns for saline/room air controls; p < .05), which was accompanied by only minimal inflammatory changes, as determined by both light microscopy and lavage cytology. Animals receiving either hyaluronidase or 60% oxygen alone showed no significant increases in air-space size compared to those given saline and exposed to room air. While the mechanisms responsible for these results are unclear, the marked increase in radiolabeling of lung elastin cross links (desmosine and isodesmosine) in animals receiving both hyaluronidase and 60% oxygen (429 vs. 168 cpm/g dry lung for saline/room air controls; p < .05), as well as a significant decrease in total lung desmosine and isodesmosine (32.5 vs. 37.7 micrograms/lung for saline/room air controls; p < .05), suggests that elastic fiber damage is a potential factor. Moreover, only those animals receiving both hyaluronidase and 60% oxygen showed a significant rise in cell free elastase activity in lavage fluids compared to saline/room air controls (83.3 vs. 48.3 ng; p < .05). On the basis of these findings, it is concluded that while elastic fiber damage may be a common pathway in emphysema, the factors that initiate the disease may be more varied than previously suspected and not always related to the balance between elastases and their inhibitors. PMID- 8467762 TI - Administration of bromodeoxyuridine in early postnatal rats results in lung changes at maturity. AB - The purpose of this study was to examine how lungs in early postnatal animals that are administered bromodeoxyuridine (BrdU), a thymidine analog known to be a cytogenetically toxic agent, change in adult life. BrdU was injected (1 mg/g body weight) intraperitoneally in suckling rats on day 6 after birth. Immunohistochemical studies revealed that BrdU was incorporated in alveolar cells, and infrequently in the mesothelium, endothelium, and bronchiolar epithelium. The number (per high-power field) of alveolar cells incorporating BrdU was 8.76 +/- 0.50 in the interstitium and 1.66 +/- 0.25 in the epithelium. The animals were sacrificed at 2 and 8 weeks and 12 months of age. Control animals were treated the same as the BrdU-treated animals except for the injection of BrdU. Body weight, body size (nose-tail length), and lung weight were identical between BrdU-treated animals and control animals at all experimental periods. The histopathology and physiology of these lungs were studied. At 2 weeks of age, the BrdU-treated animals appeared morphologically and functionally similar to control animals. At 8 weeks and 12 months of age, the lungs in the BrdU-treated animals showed abnormal enlargement of the airspace, few alveoli, and less complexity in pulmonary architecture with or without increased lung compliance. These findings suggest that lung injured cytogenetically in early postnatal life may develop functional and structural abnormalities in later life. PMID- 8467763 TI - Role of protein synthesis and CD11/CD18 adhesion complex in neutrophil emigration into the lung. AB - The mechanism of neutrophil (PMN) emigration into the lung may be stimulus dependent. This study examined PMN emigration in the lung induced by intratracheal instillation of lipopolysaccharide (LPS), Streptococcus pneumoniae (S. pneu) organisms, supernatant from S. pneu incubated with alveolar macrophages (AM phi), Escherichia coli (E. coli) organisms, or phorbol myristate acetate (PMA). Rabbits were pretreated with either the CD18 monoclonal antibody (MAb) 60.3, the protein synthesis inhibitor cycloheximide (Cx), or, in one case, both. Animals were then given one of the above stimuli to elicit PMN emigration. Four hours after the stimulus was instilled, animals were killed and total and differential cell counts were performed on bronchoalveolar lavage (BAL) fluid. PMN emigration in response to PMA was virtually abolished by MAb 60.3, but was not significantly inhibited by Cx. Emigration induced by LPS was inhibited by 80% by either MAb 60.3 or Cx, and greater than 94% when MAb 60.3 and Cx were given simultaneously. Emigration in response to E. coli organisms was 80% inhibited by MAb 60.3. Emigration induced by S. pneu was approximately 50% inhibited by MAb 60.3, but was greater than 90% blocked by Cx. The MAb 60.3 had approximately the same effect on PMN emigration toward the supernatant from co-incubation of AM phi with S. pneu as it did toward live S. pneu. It is concluded that the mechanism of PMN emigration into the lung is stimulus-dependent. The CD18-dependent mechanism is responsible for the majority of the emigration in response to PMA, E. coli LPS, and E. coli organisms. S. pneu and supernatant from S. pneu + AM phi produce a CD18-independent pathway. These data suggest the requirement for de novo protein synthesis for PMN emigration in response to LPS and S. pneu, but not for PMA-induced emigration. PMID- 8467764 TI - Clearance of 99mTc-labeled albumin from lungs in anesthetized guinea pigs. AB - Gamma imaging was used to measure the rate of clearance of aerosolized 99mTc human serum albumin (HSA) from the lungs of control guinea pigs and guinea pigs that received increased lung inflation or lung injury. Anesthetized guinea pigs were ventilated for 6 min with an aerosol of HSA and the radioactivity in the chest was monitored for 2 h with a gamma camera to determine whether the clearance rate would be a reliable assessment of lung epithelial permeability. Increased lung volumes were effected by application of 5 or 7 cm H2O positive end expired pressure (5-PEEP and 7-PEEP, respectively). Lung injury was induced either by intravenous oleic acid (OA, 27-73 microliters/kg) or inhalation of nitrogen dioxide (NO2, 80-100 ppm) for 2 h. Postmortem extravascular lung water volume (EVLW) provided an assessment of the degree of lung injury. Tracer clearance rates in animals receiving 5 or 7 cm H2O PEEP were not significantly different from controls (K = 0.15 +/- 0.05 and 0.24 +/- 0.10 vs 0.12 +/- 0.03%/min, respectively, p > .05). Animals exposed to NO2 had faster tracer clearance rates (K = 0.33 +/- 0.21%/min, p < .05) and higher EVLW (5.8 +/- 3.0 vs 3.7 +/- 0.2 mL/g dry lung, p < .05) than controls. Clearance rates of HSA from the lungs of NO2-exposed guinea pigs correlated well with injury as assessed by EVLW (r = .93, p < .01). Clearance rates of HSA and EVLW in animals receiving oleic acid were significantly higher than controls and the group receiving 5 cm H2O PEEP (K = 0.58 +/- 0.41%/min, EVLW = 8.1 +/- 0.8 mL/g dry lung tissue, p < .05), but there was no correlation between these parameters in this injury model. It is concluded that imaging of the disappearance of radiolabeled HSA in the guinea pig can be a useful index of lung epithelial permeability, but this technique is limited to certain models of lung injury. PMID- 8467765 TI - Cellular and cytokine profiles in spontaneous regression phase of hypersensitivity pneumonitis. AB - The phase of spontaneous regression of hypersensitivity pneumonitis was evaluated using a mouse model. C57BL/6 mice were instilled intranasally with 150 micrograms of the thermophilic actinomycete Faeni rectivirgula 3 days a week so as to establish a mouse model of farmer's lungs. It was shown that instillation of mice for a period of more than 6 weeks was associated with a significant decrease in the lung inflammation, suggestive of the so-called spontaneous regression phase seen in this pathology. Indeed, the lung index was seen to decrease after more than 6 weeks of treatment (2.2 after 6 weeks vs. 1.7 at 12 weeks, p < .01). There was also a significant decrease in lung hydroxyproline levels in animals given 12 weeks of treatment (175 micrograms/lung) compared to 6-week-treated animals (212 micrograms/lung, p < .05). Treated mice did not show a significant decrease in the alveolitis after 9 weeks of treatment. Also, there was no evidence that there was a decrease in bronchoalveolar lavage macrophage or T lymphocyte activity in mice given more than 9 weeks of F. rectivirgula treatment, as judged by O2- release and antigen-driven proliferation. Conversely, it was shown that NK cell activity in the lung digest of mice given 9 to 12 weeks of instillation was significantly higher than that seen in mice given 6 weeks of treatment. Analysis of the lung cell cytokine profile seen after ConA mitogenesis showed that after 6 weeks of F. rectivirgula treatments, nonparenchymal cells secreted high levels of tumor necrosis factor alpha (TNF alpha) and granulocyte macrophage colony stimulating-factor (GM-CSF), whereas similar cells from the lungs of mice given 9 12 weeks of treatment secreted larger amounts of interferon-gamma (IFN gamma) and interleukin-2 (IL-2). Overall, these results suggest that the spontaneous regression phase is associated with changes in NK cell activity and lung cell lymphokine profile. PMID- 8467766 TI - Elastase causes secretory discharge in bronchi of hamsters with elastase-induced secretory cell metaplasia. AB - A single intratracheal instillation of human neutrophil elastase (HNE) into hamsters causes granule discharge from bronchial secretory cells followed by marked accumulation of granules, visible by light microscopy at 21 days and persisting through 18 months. To determine whether persistence of this secretory cell metaplasia (SCM) is due to inability of the metaplastic secretory cells to secrete their granules, hamsters having HNE-induced SCM were challenged with the potent secretagogue HNE. Four groups of 10 hamsters each received 300 micrograms HNE intratracheally. Twenty-one days later, hamsters were intratracheally treated with HNE or saline; the groups were designated HNE-HNE and HNE-SAL, respectively. Hamsters were killed 2 h or 21 days following the second treatment. Using light microscopy, nucleated epithelial cells were counted in plastic sections of the left main intrapulmonary bronchus. Cells were classified as ciliated (C), basal (B), indeterminate (IN), or secretory. Secretory cells were subcategorized as S0 (0 granules), S1 (1-4 granules), S2 (> or = 5 granules with intervening cytoplasm), and S3 (abundant granules completely filling the cytoplasm). At 2 h, S3 cell frequency in the HNE-HNE group was 13.0 +/- 2.2 (% mean +/- SE), significantly lower than in the 2 h HNE-SAL group (31.1 +/- 4.5). Concomitantly, higher cell frequencies were seen in the other secretory categories of the HNE HNE group compared to the HNE-SAL group; S2 17.1 +/- 1.9 compared to 9.4 +/- 1.9, S1 2.4 +/- 0.4 compared to 1.1 +/- 0.5, and S0 2.4 +/- 0.5 compared to 1.1 +/- 0.5, respectively. The S3 cell frequency of the 21-day HNE-HNE group was 25.4 +/- 4.7, increased significantly compared to the 2 h HNE-HNE group; this change was concomitant with significant decrease in the frequency of the S0 secretory cells. Cell frequencies of C, B, and IN were not affected by treatment or time. It is concluded that metaplastic secretory cells discharge their granules in response to HNE; SCM returns to its original state after HNE rechallenge; persistent SCM is not due to the inability of metaplastic secretory cells to discharge their granules. PMID- 8467767 TI - Recognition of Pneumocystis carinii in foals with respiratory distress. AB - Five 3-month-old foals presenting with fever and respiratory disease were found to have pulmonary abscesses with patchy to diffuse alveolar and interstitial pneumonia on post-mortem examination. All affected foals had evidence of Rhodococcus equi infection and had few to abundant Pneumocystis carinii cysts in the sections of affected lung. Of the 5 foals examined radiographically, 3 had a distinct reticulonodular (miliary) pattern which may aid in the ante-mortem diagnosis of P. carinii pneumonia (PCP). Leukocyte counts of foals with PCP were significantly greater than in the control group of foals with uncomplicated bacterial pneumonia. Foals with PCP tended to be more tachypnoeic than the control foals and 4 of the 5 PCP+ foals appeared dyspnoeic before death. The ante mortem recognition of PCP may be expedited by bronchoalveolar lavage and successful treatment of foals with PCP may require the administration of adequate levels of potentiated sulphonamides. PMID- 8467769 TI - Clinical evaluation of an infusion of xylazine, guaifenesin and ketamine for maintenance of anaesthesia in horses. AB - General anaesthesia was maintained in 40 horses by the continuous intravenous infusion of a mixture of 500 ml 10% guaifenesin solution, 1 g ketamine and 500 mg xylazine. The median duration of infusion was 65 mins (interquartile range 51-95 mins). Anaesthesia was characterised by active palpebral reflexes, variable degrees of nystagmus and occasional swallowing. Swallowing was considered to be undesirable in horses undergoing laryngeal surgery, but the infusion produced satisfactory conditions for all other surgical procedures performed. Arterial blood pressure was well maintained in all cases (median mean arterial blood pressure = 85 mmHg after 30 mins anaesthesia). Heart rate and PaCO2 were significantly lower, whilst PaO2 was significantly higher in the infusion group than in a group of paired control horses which were anaesthetised with halothane. Recovery from anaesthesia was good (Grades 1-2) in 33 horses. Median times to sternal recumbency and to standing were 24 and 38 mins respectively. The infusion caused a significant fall in packed cell volume, haemoglobin concentration and red blood cell count (P < 0.01) and a significant rise in plasma glucose concentration (P < 0.01). These variables returned to pre-infusion values within 24 h. PMID- 8467768 TI - Effect of surgical removal of endometrial cups on concentrations of chorionic gonadotrophin and subsequent fertility in the mare. AB - Seven pregnant mares underwent general anaesthesia, laparotomy, hysterotomy and removal of a 50-day conceptus. Eversion of the uterine horn through the hysterotomy site allowed direct visualisation and electrosurgical removal of endometrial cup tissue from 5 randomly selected mares (Nos 1-5), while cup tissue in 2 mares (Nos 6 and 7) was left intact. Two pregnant mares served as unoperated controls (Nos 8 and 9). Efforts to re-establish pregnancy were initiated 20 days after surgery. Serum samples collected before surgery and during the post operative period were analysed for concentration of horse chorionic gonadotrophin (CG) by radioimmunoassay. Mean (+/- sd) weight and area of removed tissue was 9.91 +/- 4.6 g and 22.4 +/- 5.9 cm2, respectively. Concentrations of CG ranging from 3440 to 21,220 ng/ml were highest at the time of cup removal (50 days) and declined thereafter. Peak concentrations of CG at the time of surgery were not linearly correlated (r = -0.59) with mass of excised cup tissue. Individual CG half-life values for Mares 1-5 ranged from 5.4 to 8.8 days (mean 7.1 +/- 1.2 days). Peak CG concentrations occurred 68 days after conception with a rate of disappearance (half-time) of 13.4 +/- 0.4 days in Mares 6 and 7 and at 74 and 78 days after conception with a half-time of 14.0 +/- 5.7 days in Mares 8 and 9. Mares 1-5 exhibited behavioural oestrus and ovulation 30-44 days after surgery. Pregnancy occurred in 3 mares within 41 days after surgery and was associated with concentrations of CG below 200 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467770 TI - An immunohistological study of MHC class II expression and T lymphocytes in the endometrium of the mare. AB - The distribution of T lymphocytes and of cells bearing MHC Class II antigens in the endometrium of the mare was studied using an avidin-biotin-peroxidase staining method. The cells within the endometrium which expressed MHC Class II were macrophages, lymphocytes, monocytes, dendritic cells, epithelial cells and endothelial cells. MHC Class II expression increased significantly (P < 0.05) in the luminal epithelium and tended (P = 0.0573) to increase in the subepithelial layers during oestrus. Numbers of T lymphocytes did not differ between oestrus and dioestrus. MHC Class II expression and T lymphocyte numbers were not significantly different in samples collected on Day 14 of dioestrus and on Day 14 of pregnancy. The presence of endometritis greatly increased MHC Class II expression and T lymphocyte numbers within the endometrium. PMID- 8467772 TI - Ground reaction force patterns of Dutch warmblood horses at normal trot. AB - This study was undertaken to establish limb loading patterns of sound horses at the trot, to provide a data base against which results for lame horses could be compared. Ground reaction force (GRF) data were collected from 20 clinically sound Dutch Warmblood horses. The data from at least 5 stance phases of each limb were averaged after standardisation to the animal's body mass and to the stance phase duration and resulted in 'representative' GRF data. The symmetry in the vertical GRF peak amplitudes, impulses and the stance phase duration comparing left and right limbs exceeded 97%. By averaging the 'representative' GRF of the 20 horses a 'standard' GRF pattern of the Dutch Warmblood horse at the trot was constructed. The GRF patterns at the trot, compared with those at the walk, showed only one vertical force peak in forelimbs and hindlimbs (11.59 N/kg and 10.21 N/kg, respectively). The retardatory and propulsory forces were distributed over the forelimbs and hindlimbs in such a way that the forelimbs contributed more to retardation (peak forces 1.13 and 0.79 N/kg), and the hindlimbs more to propulsion (-0.84 and -1.17 N/kg, respectively). PMID- 8467771 TI - Communication of the ulnaris lateralis bursa with the equine elbow joint and evaluation of caudal arthrocentesis. AB - Elbows from cadaver limbs were evaluated to determine the presence of a communication between the ulnaris lateralis bursa (ULB) and the joint and the extent of the bursa. Thirty-two pairs of joints were studied: 12 pairs were frozen, then transversely sectioned and 20 pairs were injected with methyl methacrylate. The 12 frozen-section pairs revealed a communication between the ULB and the elbow joint in 9/24 joints (37.5%) and a true bursa (absence of communication) in 15/24 joints (62.5%). The mean bursal length in adult horses was 3.8 cm. There was no significant difference in the length of the bursa or presence of bursa-joint communication between the right and left limbs. In the acrylic specimens a communication between the ULB and the joint was found in 19/40 specimens (47.5%). There was no significant correlation between age or sex and frequency of communication. There was a significantly greater prevalence of communications present in Quarter Horse than in non-Quarter Horse (P < 0.05) joints. A communication between the ULB and the joint is not always present, and therefore injection of the elbow joint via the ULB may be unreliable. PMID- 8467773 TI - Flunixin meglumine blocks frusemide-induced bronchodilation in horses with chronic obstructive pulmonary disease. AB - Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg every 8 h for 2 days before the experiment). Frusemide significantly reduced the delta Pplmax beginning 15 mins after drug administration. This effect persisted for 5 h. The reduction in delta Pplmax was due partly to an increase in dynamic compliance and partly to a decrease in pulmonary resistance. Tidal volume and respiratory frequency were unaffected by frusemide. Vehicle had no effect on lung function. Flunixin meglumine abolished the effect of frusemide on airway calibre but did not prevent diuresis. These results indicate that the effect of frusemide on airways of horses with heaves persists for at least 5 h, is mediated through prostanoids, and is not a result of diuresis. PMID- 8467774 TI - Muscle characteristics in standardbreds of different ages and sexes. AB - Biopsy samples were taken from the middle gluteal muscle in 107 health Standardbred horses. The horses were separated according to sex and divided into 4 age groups (1, 2, 3 and 4-6 years). The proportion of Type I fibres increased with age (from 16 to 20%), irrespective of sex. The proportions of Type IIA and IIB fibres varied with age and differed between stallions and mares. Type IIA fibres increased in mares from 37 to 47% and in stallions from 40 to 48% and Type IIB fibres decreased from 49 to 34% in mares, and from 43 to 30% in stallions. Mares and stallions did not differ in enzyme activities, which changed with age. The activity of citrate synthase increased from 30 to 62 mmol/kg/min and that of lactate dehydrogenase decreased from 1,930 to 1,565 mmol/kg/min. The relative area of each fibre type was measured in biopsy samples from 7 mares and 7 stallions aged 1 year and 7 mares and 11 stallions aged 4-6 years. The relative areas of Type IIA and IIB fibres changed with age and differed between sexes. The relative area of Type IIA fibres increased in mares from 30 to 35% and in stallions from 33 to 47% and that of Type IIB fibres decreased in mares from 63 to 54% and in stallions from 55 to 38% between the ages of 1 and 4-6 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467775 TI - Factors influencing the outcome of equine anaesthesia: a review of 1,314 cases. AB - Patient data, physiological variables and recovery quality were extracted from 1,314 records of equine anaesthetics covering a 7-year period and analysed retrospectively. Better recovery quality was significantly associated with shorter duration of anaesthesia, longer recovery times, less invasive surgery, a lower pulse rate at induction and higher pulse and respiratory rates during anaesthesia. Nineteen animals suffered serious anaesthetic-related problems (1.4% incidence) and 9 died (0.68% incidence). Clinical treatment of hypotension during anaesthesia significantly reduced the hypotensive index but did not significantly alter the recovery quality or incidence of post-anaesthetic myopathy. The severity of the myopathy was, however, markedly reduced in the animals treated for hypotension. PMID- 8467776 TI - Failure of hydroxyprogesterone caproate to maintain pregnancy in ovariectomised mares. PMID- 8467777 TI - Recurrent diarrhoea in aged ponies associated with larval cyathostomiasis. PMID- 8467778 TI - Sterility associated with an XO karyotype in a miniature horse mare. PMID- 8467779 TI - Localised subcutaneous cryptococcal granuloma in a horse. PMID- 8467780 TI - Factors associated with the risk of developing sarcoid tumours in horses. PMID- 8467781 TI - Comparison of two surgical methods for treatment of crib-biting in horses. PMID- 8467782 TI - Comparison of two surgical methods for treatment of crib-biting in horses. PMID- 8467783 TI - 'Frozen' evolution of equine influenza viruses? PMID- 8467784 TI - Immunodeficiency and serious pneumonia in foals: the plot thickens. PMID- 8467785 TI - Progesterone and the pregnant mare: unanswered chestnuts. PMID- 8467786 TI - A comparison of responses to analgesia of the navicular bursa and intra-articular analgesia of the distal interphalangeal joint in 59 horses. AB - Analgesia of the distal interphalangeal (DIP) joint and of the navicular bursa was performed independently in the lame or lamer forelimb of 59 horses, in which lameness was significantly improved by perineural analgesia of either the palmar digital or palmar (abaxial sesamoid) nerves. In 3 horses no improvement was detected. Lameness was improved by analgesia of the DIP joint but there was no response to analgesia of the navicular bursa in 3 horses. In 12 horses, lameness was improved by analgesia of the navicular bursa but intra-articular analgesia resulted in no change. Forty-one horses responded both to analgesia of the navicular bursa and intra-articular analgesia of the DIP joint. Synovial fluid was retrieved from all DIP joints but from only one navicular bursa. It is suggested that a positive response to analgesia of the DIP joint does not necessarily imply that pain arises from the joint per se, but a positive response to intra-bursal analgesia probably reflects pathology of the bursa per se, the navicular bone and/or supporting ligaments and/or the DDFT. Radiographic abnormalities of the navicular bone in the lame or lamer limb were detected in 35 horses, all of which showed some response to analgesia of the navicular bursa. In 25 of these horses (71%) changes were only identifiable in the palmaroproximal palmarodistal oblique views.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467787 TI - Growth phase dependence of the activation of a bacterial gene for carotenoid synthesis by blue light. AB - Myxococcus xanthus responds to blue light by producing carotenoid pigments. A mutation at a gene named carC is known to block the metabolism of phytoene, a carotenoid precursor, and this gene has now been cloned and sequenced. We show here that gene carC, which is homologous to phytoene dehydrogenase genes from other organisms, is tightly regulated by light through a mechanism that operates only when the cells have reached the stationary phase or are starved of a carbon source. A genetic element that mediates the effect of the growth phase has been identified. Gene carC is integrated with another unlinked carotenogenic gene in a single 'light regulon' controlled by common trans-acting genetic elements. A potential -35 site for the binding of sigma factors has been found upstream of the carC transcriptional start. However, the -10 region shows no similarity with analogous sites at promoters of other Gram-negative bacteria. PMID- 8467788 TI - Excess capacity of H(+)-ATPase and inverse respiratory control in Escherichia coli. AB - With succinate as free-energy source, Escherichia coli generating virtually all ATP by oxidative phosphorylation might be expected heavily to tax its ATP generating capacity. To examine this the H(+)-ATPase (ATP synthase) was modulated over a 30-fold range. Decreasing the amount of H(+)-ATPase reduced the growth rate much less than proportionally; the H(+)-ATPase controlled growth rate by < 10%. This lack of control reflected excess capacity: the rate of ATP synthesis per H(+)-ATPase (the turnover number) increased by 60% when the number of enzymes was decreased by 40%. At 15% H(+)-ATPase, the enzyme became limiting and its turnover was increased even further, due to an increased driving force caused by a reduction in the total flux through the enzymes. At smaller reductions of [H(+) ATPase] the total flux was not reduced, revealing a second cause for increased turnover number through increased membrane potential: respiration was increased, showing that in E.coli, respiration and ATP synthesis are, in part, inversely coupled. Indeed, growth yield per O2 decreased, suggesting significant leakage or slip at the high respiration rates and membrane potential found at low H(+) ATPase concentrations, and explaining that growth yield may be increased by activating the H(+)-ATPase. PMID- 8467789 TI - Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. AB - Two crystal structures are described for the lysosomal aspartic protease cathepsin D (EC 3.4.23.5). The molecular replacement method was used with X-ray diffraction data to 3 A resolution to produce structures for human spleen cathepsin D and for bovine liver cathepsin D complexed with the 6-peptide inhibitor pepstatin A. The lysosomal targeting region of cathepsin D defined by previous expression studies [Barnaski et al. (1990) Cell, 63, 281-219] is located in well defined electron density on the surface of the molecules. This region includes the putative binding site of the cis-Golgi phosphotransferase which is responsible for the initial sorting step for soluble proteins destined for lysosomes by phosphorylating the carbohydrates on these molecules. Carbohydrate density is visible at both expected positions on the cathepsin D molecules and, at the best defined position, four sugar residues extend towards the lysosomal targeting region. The active site of the protease and the active site cleft substrate binding subsites are described using the pepstatin inhibited structure. The model geometry for human cathepsin D has rms deviations from ideal of bonds and angles of 0.013 A and 3.2 degrees respectively. For bovine cathepsin D the corresponding figures are 0.014 A and 3.3 degrees. The crystallographic residuals (R factors) are 16.1% and 15.8% for the human and inhibited bovine cathepsin D models respectively. The free R factors, calculated with 10% of the data reserved for testing the models and not used for refinement, are 25.1% and 24.1% respectively. PMID- 8467790 TI - The portal protein of bacteriophage SPP1: a DNA pump with 13-fold symmetry. AB - Electron microscopy in combination with image processing is a powerful method for obtaining structural information on non-crystallized biological macromolecules at the 10-50 A resolution level. The processing of noisy microscopical images requires advanced data processing methodologies in which one must carefully avoid the introduction of any form of bias into the data set. Using a novel multivariate statistical approach to the analysis of symmetry, we studied the structure of the bacteriophage SPP1 portal protein oligomer. This portal structure, ubiquitous in icosahedral bacteriophages which package dsDNA, is located at the site of symmetry mismatch between a 5-fold vertex of the icosahedral shell and the 6-fold symmetric (helical) tail. From previous studies such 'head-to-tail connector' structures were generally accepted to be homododecamers assembled in a 12-fold symmetric ring around a central channel. Using a new analysis methodology we have found that the phage SPP1 portal structure exhibits 13-fold cyclical symmetry: a new point group organization for oligomeric proteins. A model for the DNA packaging mechanism by 13-fold symmetric portal protein assemblies is presented which attributes a coherent functional meaning to their unusual symmetry. PMID- 8467791 TI - Structure of the HMG box motif in the B-domain of HMG1. AB - The conserved, abundant chromosomal protein HMG1 consists of two highly homologous, folded, basic DNA-binding domains, each of approximately 80 amino acid residues, and an acidic C-terminal tail. Each folded domain represents an 'HMG box', a sequence motif recently recognized in certain sequence-specific DNA binding proteins and which also occurs in abundant HMG1-like proteins that bind to DNA without sequence specificity. The HMG box is defined by a set of highly conserved residues (most distinctively aromatic and basic) and appears to define a novel DNA-binding structural motif. We have expressed the HMG box region of the B-domain of rat HMG1 (residues 88-164 of the intact protein) in Escherichia coli and we describe here the determination of its structure by 2D 1H-NMR spectroscopy. There are three alpha-helices (residues 13-29, 34-48 and 50-74), which together account for approximately 75% of the total residues and contain many of the conserved basic and aromatic residues. Strikingly, the molecule is L shaped, the angle of approximately 80 degrees between the two arms being defined by a cluster of conserved, predominantly aromatic, residues. The distinctive shape of the HMG box motif, which is distinct from hitherto characterized DNA binding motifs, may be significant in relation to its recognition of four-way DNA junctions. PMID- 8467792 TI - The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells. AB - Retroviral oncogenes encode nuclear regulators of gene expression or signal transduction molecules, such as protein kinases, which stimulate the activity of cellular transcription factors. Here we describe the cloning of NF-M, a myeloid specific transcription factor related to C/EBP beta, which is a target of activated protein kinases. NF-M stimulates the expression of the gene encoding cMGF, a myeloid cell-specific growth factor, creating an autocrine growth loop crucial to oncogene transformation of myeloid cells. The NF-M protein bound directly to the cMGF gene promoter and activated its transcription, even in erythroid cells where the promoter is usually inactive. In addition, a truncated, dominant-negative form of NF-M inhibited cMGF expression in macrophages, indicating that NF-M is required for the normal activation of the gene. When multipotent hematopoietic progenitor cells were stimulated to differentiate, NF-M expression was induced at a very early stage, suggesting that the transcription factor plays a role in lineage commitment. The stimulation of transformed myelomonocytic cells or of normal peripheral blood macrophages with kinases or LPS or TPA respectively, led to the rapid redistribution of NF-M protein from the cell bodies to the nucleus, consistent with the notion that NF-M was directly affected by such treatments. Our data indicate that NF-M plays a key role in myelomonocytic differentiation, in signal transduction during macrophage activation and in the development of myelogenous leukemia. PMID- 8467793 TI - Influence of the v-Myb transactivation domain on the oncoprotein's transformation specificity. AB - The v-myb-containing viruses AMV and E26 induce the proliferation of myelomonocytic cells. The E26 Myb protein, by virtue of its fusion to Ets, is also able to transform multipotent haematopoietic cells (MEPs). We have examined the biological effects of substituting the v-Myb transactivation domain with the strong acidic activator domain from the C-terminus of the HSV-1 VP16 protein. In the absence of Ets, deletion of the transactivation domain destroyed the ability of v-Myb to stimulate transcription and to transform cells, whilst the substitution of the VP16 transactivation domain into v-Myb resulted in a greatly enhanced transactivation potential and altered TATA box binding protein (TBP) binding properties. In spite of these functional differences, the v-Myb VP16 protein regained the ability to transform myeloid cells with the same characteristics as wild type v-Myb. A construct encoding v-Myb VP16 fused to v Ets was still capable of inducing leukaemia and of transforming both myeloid cells and MEPs in vitro, although the latter cells exhibited an altered phenotype. Our results demonstrate that the transformation of myeloid cells by v Myb is largely independent of the type and potency of the transactivation domain it contains, whereas transformation of MEPs by the Myb-Ets fusion protein has more stringent transactivation requirements of Myb. PMID- 8467794 TI - Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter. AB - Metallothioneins (MTs) are small cysteine-rich proteins whose structure is conserved from fungi to man. MTs strongly bind heavy metals, notably zinc, copper and cadmium. Upon exposure of cells to heavy metal and other adverse treatments, MT gene transcription is strongly enhanced. Metal induction is mediated by several copies of a 15 bp consensus sequence (metal-responsive element, MRE) present in the promoter region of MT genes. We and others have demonstrated the presence of an MRE-binding factor in HeLa cell nuclear extracts. We found that this factor, termed MTF-1 (MRE-binding transcription factor) is inactivated/reactivated in vitro by zinc withdrawal/addition. Here we report that the amounts of MTF-1-DNA complexes are elevated several-fold in zinc-treated cells, as measured by bandshift assay. We have also cloned the cDNA of mouse MTF 1, a 72.5 kDa protein. MTF-1 contains six zinc fingers and separate transcriptional activation domains with high contents of acidic and proline residues. Ectopic expression of MTF-1 in primate or rodent cells strongly enhances transcription of a reporter gene that is driven by four consensus MREd sites, or by the complete mouse MT-I promoter, even at normal zinc levels. PMID- 8467795 TI - Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells. AB - KRAB zinc-finger proteins (KRAB-ZFPs) constitute a large subfamily of ZFPs of the Kruppel C2H2 type. KRAB (Kruppel-associated box) is an evolutionarily conserved protein domain found N-terminally with respect to the finger repeats. We report here the characterization of a particular subgroup of highly related human KRAB ZFPs. ZNF91 is one representative of this subgroup and contains 35 contiguous finger repeats at its C-terminus. Three mRNA isoforms with sequence identity to ZNF91 were isolated by the polymerase chain reaction. These encode proteins with a KRAB domain present, partially deleted or absent. Five genomic fragments were characterized, each encoding part of a gene: the ZNF91 gene or one of four distinct, related KRAB-ZFP genes. All exhibit a common exon/intron organization with the variant zinc finger repeats organized in a single exon and the KRAB domain encoded by two separate exons. This positioning of introns supports the hypothesis that the mRNA isoforms encoding polypeptides with variability in the KRAB domain could arise by alternative splicing. By in situ chromosomal mapping studies and by analysis of fragments from a human genomic yeast artificial chromosome library containing KRAB-ZFP genes, we show that these genes occur in clusters; in particular, a gene complex containing over 40 genes has been identified in chromosomal region 19p12-p13.1. These ZNF91-related genes probably arose late during evolution since no homologous genes are detected in the mouse and rat genomes. Although the transcription of members of this KRAB-ZFP gene subgroup is detectable in all human tissues, their expression is significantly higher in human T lymphoid cells. PMID- 8467796 TI - GAL4 is regulated by a glucose-responsive functional domain. AB - The Saccharomyces cerevisiae transcriptional activator GAL4 is regulated by the presence of available carbon sources. Galactose induces activity by inhibiting the negative regulator GAL80, while glucose, the preferred carbon source, antagonizes GAL4 function by several mechanisms. In the present study we present evidence that one mechanisms for inhibition of GAL transcription by glucose involves direct inhibition of the GAL4 protein. We demonstrate that a large, previously uncharacterized, central region of GAL4 contains at least three 'inhibitory domains' and a 'glucose response domain' (GRD). Deletion of the entire central region eliminates direct inhibition of GAL4 by glucose, and furthermore, fusion of the central region to a heterologous transcriptional activator confers inhibition by glucose. The central region inhibitory domains constitutively inhibit transcriptional activation when the GRD is absent. Direct inhibition of GAL4 activity can be detected within 30 min following glucose addition and may represent an early mechanism promoting a switch from galactose to glucose utilization. A model for the regulatory role of the central region is presented, involving interaction with an additional protein that inhibits GAL4 activity when glucose is present. PMID- 8467798 TI - The control in cis of the position and the amount of the ARG4 meiotic double strand break of Saccharomyces cerevisiae. AB - During meiosis, a transient DNA double-strand break (DSB) occurs in the promoter region (positions -200/-185) of the Saccharomyces cerevisiae ARG4 gene and is a likely intermediate in the initiation of meiotic gene conversion events in this region. We report here a functional analysis of the ARG4 DSB based on the study of various deletions in this chromosomal region. We have identified several cis acting elements located within the -465/+3 region of the ARG4 promoter that control the formation of this DSB. The -465/-317 region includes a transcription terminator and is necessary for a normal amount of ARG4 DSB, but not for its positioning. The -316/-140 region can be replaced by an unrelated DNA sequence where a meiotic DSB then occurs, suggesting that the site of DSB is not sequence specific, but is positioned at a fixed distance from the adjacent -139/+3 region. Also, in all strains constructed, the amount of meiotic DSB is correlated with the frequency of gene conversion in ARG4, which provides a strong argument for the initiation of gene conversion by a DSB in this region of the yeast genome. PMID- 8467797 TI - Functional conservation of vertebrate seven-up related genes in neurogenesis and eye development. AB - Several members of the steroid receptor superfamily, including the transcription factor COUP, are closely related to the Drosophila gene seven-up (svp) which is required for the development of the embryonic central nervous system (CNS) and specific photoreceptor cells of the eye. We have identified and characterized two zebrafish (Brachydanio rerio) members of this subfamily of orphan nuclear receptors. While one of them (svp[44]) is the zebrafish cognate of COUP, the second (svp[46]) seems to be a novel member of the COUP/svp group. The proteins encoded by both genes contain highly conserved DNA-binding and putative ligand binding domains, indicating close similarities in target sequence recognition and ligand binding. Analysis of the spatial distribution of their transcripts in whole-mount embryos revealed that the CNS is a major site of expression for both genes. At early embryonic stages, both genes are expressed in domains corresponding to specific rhombomere primordia in the hindbrain. This suggests an involvement in hindbrain segmentation and/or rhombomere specification. Moreover, transcripts derived from both genes are detected within distinct areas of the eye rudiments, suggesting roles in eye patterning and/or cell differentiation. In the case of the svp[44] gene, expression is also observed within specific parts of the midbrain, diencephalon and telencephalon. These results represent the first evidence that at least some of the nervous system and eye-specific functions of Drosophila svp are conserved in vertebrates. PMID- 8467799 TI - Conserved features in the mode of replication of eukaryotic ribosomal RNA genes. AB - It was previously shown that a 1.5 kb fragment located in the non-transcribed spacer (NTS) is the earliest replicating region of pea (Pisum sativum) rDNA in synchronized root cells. In the present report the structure of this region was characterized. It contains a cluster of four 11 bp near matches to the Saccharomyces cerevisiae ARS consensus sequence (ACS). These near matches are embedded in an A+T rich domain located upstream from the transcription initiation site. We identified and mapped an intrinsic DNA bending locus 5' to the cluster of near matches. Several eukaryotic origins including the ARS from the budding yeast show very similar structural features. This observation strengthens the notion that pea rDNA replication initiates at or near this region. Replication of the entire pea rDNA repeat was analysed by two-dimensional (2D) agarose gel electrophoresis. The results obtained indicate that only a small fraction of the potential origins is used in each replication round. Forks moving in the direction opposite to rRNA transcription are stalled at a polar replication fork barrier (RFB), which mapped near the 3' end of the transcription unit. Consequently, most of pea rDNA appears to replicate in a unidirectional manner. These results show that the strategy used to replicate pea and yeast rRNA genes is very similar, suggesting that it has been conserved and might be common to most eukaryotes. PMID- 8467800 TI - A methyl jasmonate-induced shift in the length of the 5' untranslated region impairs translation of the plastid rbcL transcript in barley. AB - The plant growth substance (-)-jasmonic acid methyl ester (methyl jasmonate, JaMe) affects plastid gene expression at the protein and mRNA levels when applied exogenously to detached leaf segments of Hordeum vulgare L. cv. Salome. Translation of the large subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (LSU, rbcL gene products) and of the 65 and 68 kDa proteins of photosystem I (psaA and psaB gene products, respectively) ceased, whereas synthesis of the 32 kDa photosystem II protein (D1, psbA gene product) continued in JaMe-treated leaf tissues. These changes were not caused by corresponding alterations in transcript abundances. The loss of LSU protein synthesis, occurring within 24 h of JaMe treatment, correlated with a decline in the in vitro-translatable rbcL mRNA, but contrasted with an almost constant transcript level. The 5' ends of the rbcL transcripts shifted from '-59' in freshly harvested or water-treated leaves to '-94' in JaMe-treated leaf tissues. Transcripts ending at these positions presumably arise from alternative processing of the primary transcript ending at position '-316'. The '-94' transcript contains, within the 5' untranslated region, a 35-base motif with remarkable complementarity to the extreme 3' terminal part of the 16S rRNA, involved in intramolecular base pairing within the ribosome and can associate with 30S but not 70S complexes in organello, suggesting that intermolecular base pairing impairs translation initiation, probably by competing for ribosome binding at the Shine-Dalgarno sequence. In contrast, transcripts ending at '-59' lack the 5' terminal 'extra' sequence and are active in terms of translation initiation. PMID- 8467801 TI - Related chromosome binding sites for zeste, suppressors of zeste and Polycomb group proteins in Drosophila and their dependence on Enhancer of zeste function. AB - Polycomb group genes are necessary for maintaining homeotic genes repressed in appropriate parts of the body plan. Some of these genes, e.g. Psc, Su(z)2 and E(z), are also modifiers of the zeste-white interaction. The products of Psc and Su(z)2 were immunohistochemically detected at 80-90 sites on polytene chromosomes. The chromosomal binding sites of these two proteins were compared with those of zeste protein and two other Polycomb group proteins, Polycomb and polyhomeotic. The five proteins co-localize at a large number of sites, suggesting that they frequently act together on target genes. In larvae carrying a temperature sensitive mutation in another Polycomb group gene, E(z), the Su(z)2 and Psc products become dissociated from chromatin at non-permissive temperatures from most but not all sites, while the binding of the zeste protein is unaffected. The polytene chromosomes in these mutant larvae acquire a decondensed appearance, frequently losing characteristic constrictions. These results suggest that the binding of at least some Polycomb group proteins requires interactions with other members of the group and, although zeste can bind independently, its repressive effect on white involves the presence of at least some of the Polycomb group proteins. PMID- 8467802 TI - Implications of novel guide RNA features for the mechanism of RNA editing in Crithidia fasciculata. AB - We have determined the relative steady state concentration of the two Crithidia fasciculata guide (g)RNAs involved in editing the two domains of mRNAs for NADH dehydrogenase (ND) subunit 7. We found that, although there was an 8-fold difference between the molar ratio of these two gRNAs relative to the (pre)-mRNA, the two domains are edited with a very similar frequency (around 50%). Also, for the editing of a given domain, many gRNA species exist with the same 5' end but with a different 3' uridylation site. Approximately 20% of these short gRNAs do not contain the information required for editing a complete domain, which may explain the high incidence of partially edited RNAs. Remarkably, genomically encoded Us are missing from two sites of a few of the gRNAs involved in editing apocytochrome b RNA. We speculate that these species are created by editing-like events. Both the short and complete forms of the ND7 gRNAs are found in chimeric molecules, in which the gRNA is covalently linked via its 3'-terminus to an editing site of pre-edited ND7 RNA. Some features of the chimeric molecules are at odds with current models of RNA editing: (i) U residues are completely absent from the connecting sequence of a number of these molecules, (ii) the ND7 gRNAs are frequently hooked up to the wrong editing domain of ND7 RNA, although other gRNAs are not found at these positions and (iii) in some chimeric molecules the gRNA appears to be linked to the 5' end of pre-edited RNA. PMID- 8467803 TI - An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias. AB - In Philadelphia chromosome-positive human leukemias, which include chronic myelogenous leukemia and some acute lymphocytic leukemias, the c-abl proto oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and Bcr Abl fusion proteins are produced. The Bcr sequences activate the Abl tyrosine kinase which is required for the transforming function of Bcr-Abl. The Bcr sequences also enhance an F-actin-binding activity associated with c-Abl. Here, we show that binding of c-Abl and Bcr-Abl proteins to actin filaments in vivo and in vitro is mediated by an evolutionarily conserved domain at the C-terminal end of c-Abl. The c-Abl F-actin-binding domain contains a consensus motif found in several other actin-crosslinking proteins. Mutations in the consensus motif are shown to abolish binding to F-actin. Bcr-Abl proteins unable to associate with F actin have a reduced ability to transform Rat-1 fibroblasts and to abrogate the requirement for interleukin-3 in the lymphoblastoid cell line Ba/F3. In transformed cells, Bcr-Abl induces a redistribution of F-actin into punctate, juxtanuclear aggregates. The binding to actin filaments has important implications for the pathogenic and physiological functions of the Bcr-Abl and c Abl proteins. PMID- 8467804 TI - Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4. AB - During T cell development, precursor thymocytes that co-express the CD4 and CD8 glycoproteins give rise to mature progeny expressing one of these molecules to the exclusion of the other. Continued expression of only CD4 is the hallmark of mature helper T cells, whereas cytotoxic T cells express CD8 and extinguish CD4. The differentiation program that generates the two T cell subsets is likely to be intimately tied to regulation of expression of these cell surface molecules. We now describe the use of a murine CD4 enhancer in the generation of transgenic mice expressing physiologic levels of human CD4. The transgene is appropriately regulated during T cell development and includes the necessary cis-acting sequences for extinguishing expression in the CD8 lineage. Furthermore, in mice whose endogenous CD4 gene is inactivated, the transgenic human CD4 mediates rescue of the CD4 lineage and restoration of normal helper cell functions. The generation of these mice exemplifies a general approach for developing reliable animal models for the human immune system. PMID- 8467805 TI - Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells. AB - Programmed cell death (PCD) or apoptosis is a common form of cellular demise during embryogenesis, tumorigenesis and clonal selection in the immune system. The bcl-2 proto-oncogene has been recently implicated as a potential physiological regulator of the PCD pathway. Gene transfer studies have shown that overexpression of bcl-2 blocks apoptosis mediated by several stimuli in cultured cell lines and promotes the survival of B and T lymphocytes in transgenic mice. However, it remains unclear whether under normal conditions bcl-2 is responsible for controlling cell death. We have investigated the role of bcl-2 in the antimembrane IgM (mIgM)-induced apoptotic death of WEHI-231 B cell lymphoma, a model that mimics clonal deletion of immature B cells by antigen. Signalling of mIgM receptors triggered downregulation of both bcl-2 RNA and protein, and induced apoptosis in WEHI-231 B cells. This effect appeared to be specific since (i) the levels of beta 2-microglobulin and beta-actin RNA remain unchanged and (ii) signalling of the apoptosis-resistant B cell lymphoma line BAL-17 with anti mu was not associated with downregulation of bcl-2 RNA. However, stable expression of bcl-2 by transfection did not rescue WEHI-231 B cells from apoptosis, yet WEHI-231 cells overexpressing bcl-2 were more resistant to programmed cell death induced by heat-shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467806 TI - Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila. AB - The Drosophila diptericin gene codes for a 9 kDa antibacterial peptide and is rapidly and transiently expressed in larvae and adults after bacterial challenge. It is also induced in a tumorous Drosophila blood cell line by the addition of lipopolysaccharide (LPS). The promoter of this gene contains two 17 bp repeats located closely upstream of the TATA-box and harbouring a decameric kappa B related sequence. This study reports that the replacement of the two 17 bp repeats by random sequences abolishes bacteria inducibility in transgenic fly lines. In transfected tumorous blood cells, the replacement of both or either of the 17 bp motifs reduces dramatically LPS inducibility, whereas multiple copies significantly increase the level of transcriptional activation by LPS challenge. A specific DNA-protein binding activity is evidenced in cytoplasmic and nuclear extracts of induced blood cells and fat body. It is absent in controls. It is proposed that induction of the diptericin gene mediated by the two 17 bp repeats occurs via a mechanism similar to that of mammalian NF-kappa B. PMID- 8467807 TI - Apidaecin multipeptide precursor structure: a putative mechanism for amplification of the insect antibacterial response. AB - Apidaecins are the most prominent components of the honeybee humoral defense against microbial invasion. Our analysis of cDNA clones indicated that up to 12 of these short peptides (2 kDa) can be generated by processing of single precursor proteins; different isoforms are hereby linked in one promolecule. Assembly of the multipeptide precursors and the putative three-step maturation are strongly reminiscent of yeast alpha-mating factor. Bioactive apidaecins are flanked by the two 'processing' sequences, EAEPEAEP (or variants) and RR; joined together, they form a single unit that is repeated numerous times. The number of such repeats is variable and was reflected in the observed diversity of transcript lengths. Each such transcript is likely to be encoded by a different gene, forming a tight gene cluster. While transcriptional activation upon bacterial challenge is not exceptionally fast, the multigene and multipeptide precursor nature of the apidaecin genetic information allows for amplification of the response, resulting in a real overproduction of peptide antibiotic. Enhanced efficiency of the 'immune' response to bacterial infection through such a mechanism is, to our knowledge, unique among insects. PMID- 8467808 TI - A conserved region of the MSP-1 surface protein of Plasmodium falciparum contains a recognition sequence for erythrocyte spectrin. AB - The major surface protein MSP-1 of Plasmodium falciparum blood-stage malaria parasites contains notably conserved sequence blocks with unknown function. The recombinant protein 190L, which represents such a block, exhibits a high affinity for red blood cell membranes. We demonstrate that both 190L and native MSP-1 protein bind to the inner red blood cell membrane skeleton protein spectrin. By using overlapping peptides covering the 190L molecule, we show that the spectrin contact site of 190L is included in a linear sequence of 30 amino acid residues. Association of 190L with naturally occurring spectrin deficient red blood cells is drastically reduced. In the same cells parasite invasion is normal, but the intracellular parasite development arrests late in the trophozoite stage. A similar situation arises when synthetic peptides covering the spectrin recognition sequence of 190L are added to P.falciparum cultures. These data and the cellular localization of MSP-1 suggest the possibility that MSP-1 associates with spectrin under natural conditions. PMID- 8467809 TI - Evidence for the induction of casein kinase II in bovine lymphocytes transformed by the intracellular protozoan parasite Theileria parva. AB - Theileria parva is an obligate, intracellular, parasitic protozoan that causes East Coast fever, an acute leukemia-like disease of cattle. T. parva and the related parasite, Theileria annulata, are unique among protozoa in that their intralymphocytic stages induce transformation of bovid lymphocytes. Comparison of in vitro protein kinase activities between uninfected IL-2-dependent T lymphoblasts and T. parva-infected lymphocytes revealed a 4.7- to 12-fold increase in total phosphorylation and the induction of a group of Theileria infection-specific phosphoproteins. The enzyme that phosphorylates these substrates is a serine/threonine kinase with substrate and effector specificities of casein kinase (CK) II. Northern blot analyses revealed a 3.9- to 6.0-fold increase in CKII alpha mRNA in the infected cells relative to the controls. Furthermore, a marked increase of CKII antigen was observed on Western blots of materials prepared from the infected cell lines. The antibovine CKII antibody used in these studies immunoprecipitated a protein kinase that phosphorylated casein in a reaction that was inhibited by low (nM) quantities of heparin. Our data show marked increases of bovine CKII at the transcriptional, translational and functional levels in T. parva-infected lymphocytes, relative to quiescent cells or IL-2-dependent parental lymphoblasts. Bovine CKII thus appears to be constitutively activated in these cells and we propose that this kinase may be an important element in the signal-transducing pathways activated by Theileria in bovid lymphocytes and perhaps in some leukemic cells. PMID- 8467811 TI - Functional significance of a family of protein kinases encoded at the shaggy locus in Drosophila. AB - The characterization of the structurally complex gene shaggy is presented. This gene encodes multiple proteins with putative serine/threonine kinase activity thought to be involved in signal transduction mechanisms that take place during several patterning events throughout Drosophila development. The gene comprises two transcription units that give rise to 10 transcripts and five different proteins with a common kinase catalytic domain and overlapping patterns of expression during development. Mutational analysis of shaggy defines a single complementation group, lethality of which is associated with the loss of two major shaggy proteins. These studies allow the first definition of a true null allele. Two proteins may fulfill maternal requirements. Phenotypes of flies expressing individual shaggy proteins revealed that although there is some redundancy between the different forms they do not all carry out identical functions in vivo. However, under experimental conditions, a single form of the protein was able to carry out all known requirements. This protein probably also functions as part of a signal transduction cascade in the imaginal neuroepithelium, where cells have to choose between epidermal and neural fates. PMID- 8467810 TI - Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells. AB - Casein kinase II is a multifunctional protein kinase which has been implicated in the regulation of cell growth and differentiation. This enzyme is much more abundant in neurons than in any other cell type. The treatment of neuroblastoma cells with an antisense oligodeoxyribonucleotide which specifically results in the depletion of casein kinase II catalytic subunits blocks neuritogenesis. Accordingly, this enzyme may perform an essential role during neurite growth in developing neurons. Casein kinase II depletion induced by antisense oligodeoxyribonucleotide is accompanied by a site-specific dephosphorylation of microtubule-associated protein MAP1B (also referred to as MAP5, MAP1.X or MAP1.2), which is paralleled by a release of MAP1B from microtubules. We therefore propose that phosphorylation by casein kinase II may be required for the proper MAP1B functioning in the promotion of the assembly of microtubules which constitute the cytoskeletal scaffolding of growing axon-like neurites. PMID- 8467812 TI - Structure-function analysis of human IL-6 receptor: dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130. AB - Here, we report the analysis of the structure-function relationship of the extracellular region of human interleukin 6 receptor (IL-6R). Upon binding of IL 6, IL-6R becomes associated extracellularly with a non-IL-6-binding but signal transducing molecule, gp130, and the IL-6 signal is generated. In this region, the cytokine receptor family domain, but not the immunoglobulin-like domain, was responsible both for IL-6 binding and for signal transduction through gp130. Because a soluble, extracellular portion of IL-6R (sIL-6R) could bind IL-6 and mediate IL-6 functions through gp130, amino acid substitutions were introduced into sIL-6R by site-directed mutagenesis. The results, together with the previously proposed tertiary structure model, suggested that the amino acid residues critical for IL-6 binding have a tendency to be distributed to the hinge region between the two 'barrel'-like fibronectin type III modules and to the same side of these two 'barrels'. Amino acid residues, of which substitutions barely affected the IL-6-binding but did abolish the IL-6 signalling capability of sIL 6R, were identified and found to be located mainly in the membrane proximal half of the second barrel. sIL-6R mutants carrying such substitutions lacked the capacity to associate with gp130 in the presence of IL-6. PMID- 8467813 TI - The internalization signal and the phosphorylation site of transferrin receptor are distinct from the main basolateral sorting information. AB - Wild-type human transferrin receptor (hTfR), like endogenous canine receptor, is expressed almost exclusively (97%) at the basolateral membrane of transfected Madin-Darbey canine kidney (MDCK) cells. We investigated the role of two distinct features of the hTfR cytoplasmic domain, namely the endocytic signal and the unique phosphorylation site, in polarized cell surface delivery. Basolateral location was not altered by point mutation of Ser24-->Ala24, indicating that phosphorylation is not involved in vectorial sorting of hTfR. The steady state distribution of hTfR was partially affected by a deletion of 36 cytoplasmic residues encompassing the internalization sequence. However, 80% of the receptors were still basolateral. As assessed by pulse-chase experiments in combination with biotinylation, newly synthesized wild-type and deletion mutant receptors were directly sorted to the domain of their steady state residency. Although both receptors could bind human transferrin, endocytosis of the deletion mutant was strongly impaired at either surface. These data indicate that the predominant basolateral targeting signal of hTfR is independent of the internalization sequence. PMID- 8467815 TI - Environmental Mutagen Society. 24th annual scientific meeting. Norfolk, Virginia, April 17-22, 1993. Abstracts. PMID- 8467814 TI - Characterization of the fission yeast mcs2 cyclin and its associated protein kinase activity. AB - We have previously described the isolation of mcs2-75, a mutation obtained as an allele-specific suppressor of a dominant allele of cdc2. mcs2 was cloned and determined to be an essential gene, the product of which shares homology with the cyclin family of proteins. In contrast to the behavior of some, but not all cyclins, the mcs2 protein is constant in its abundance and localization throughout the cell cycle. A kinase activity that co-precipitates with mcs2 can be detected when myelin basic protein (MBP) is provided as an exogenous substrate. This kinase activity is constant throughout the cell cycle. mcs2 does not appear to associate with the cdc2 protein kinase or an antigenically related kinase. Finally, a protein kinase termed csk1 (cyclin suppressing kinase) was isolated as a high copy suppressor of an mcs2 mutation. csk1 is not essential, however, the level of kinase activity that co-precipitates with mcs2 is reduced approximately 3-fold in strains harboring a csk1 null allele. Therefore, csk1 may encode a protein kinase physically associated with mcs2 or alternatively may function as an upstream activator of the mcs2-associated kinase. PMID- 8467816 TI - Muscle rearrangement in patients with hemiparesis after stroke: an electrophysiological and morphological study. AB - Skeletal muscle changes were evaluated in patients suffering from hemiparesis after stroke. Concentric needle EMG and single fiber EMG of the paretic gastrocnemius medialis muscle were performed. Maximal amplitude of H, T and M responses in calf muscles of both the affected and the unaffected sides were determined by usual electrophysiological techniques. Muscle biopsy of the lateral gastrocnemius muscle of the affected side was performed to determine the distribution of fiber types and fiber sizes. Fibrillation activity and positive sharp waves occurred in paretic muscles in patients with more recent hemiparesis while the duration of motor unit potentials was prolonged in patients with long lasting disease. The H/M ratio was increased on the paretic side. The percentage of type 1 fibers was augmented in most patients with normal mean diameter and low atrophy factor. The percentage of type 2 fibers was reduced with decreased mean diameters and with a high atrophy factor. Such changes may be related to inactivity or transsynaptic degeneration of type 2 motoneurons as a consequence of the interruption of the corticospinal tract. Increased percentage of type 1 fibers may be due to a collateral reinnervation process or a motor unit type transformation. PMID- 8467817 TI - Myasthenia gravis and invasive thymoma. A 20-year experience. AB - Over the last 20 years, 15 patients with myasthenia gravis and invasive thymoma have been treated in our department. Eight of these patients underwent either nontotal excision or were not operated on due to massive invasion, while 7 underwent total excision. These 15 cases represent 6.2% of the 242 myasthenic patients treated during this period. Six of the 8 nontotal excision cases died, and 2 of the 7 total excision cases succumbed. The prognosis of total excision cases was better than that of nontotal excision cases. The overall 5-year survival rate was 73%, and the 10-year survival rate 20%. Total excision of the thymoma, if possible, and high doses of corticosteroids and combination chemotherapy for the remaining tumor seem to be the treatments of choice. PMID- 8467818 TI - Protein analyses in cerebrospinal fluid. I. Influence of concentration gradients for proteins on cerebrospinal fluid/serum albumin ratio. AB - Concentration gradients in lumbar cerebrospinal fluid (CSF) for albumin and IgG were studied in 8 healthy individuals and 44 neuropsychiatric patients by serial sampling of 6 successive portions of CSF, each containing 4 ml, in all 24 ml. Significant and identical decreases between the first (0-4th ml) and the last (21st-24th ml) portions were found for CSF-albumin (21% decrease, p < 0.0001) and CSF-IgG (21% decrease, p < 0.0001). Therefore, the CSF/serum albumin ratio also showed a significant gradient with a 21% decrease (p < 0.0001), while no gradients were found to the IgG index. These results imply that analyses of proteins in the CSF should be performed on a standardized volume of CSF, preferably the first 12 ml, to allow comparisons of scientific results between various patient groups and controls and between different laboratories and to increase the validity of protein analyses in clinical practice. PMID- 8467819 TI - Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age. AB - Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. Therefore, accurate reference values for these parameters are of utmost importance. However, current reference values are based on 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings and on groups of young students. The present study presents reference values for CSF proteins in a large sample (n = 105) of healthy individuals, with a large age-span (18-88 years of age). The parameter for the determination of the blood CSF barrier function, the CSF/serum (CSF/S) albumin ratio, was found to show an increasing variability in individuals over 45 years of age, suggesting a less stable blood-CSF barrier function than in younger individuals. The upper reference limit for the CSF/S albumin ratio was 6.8 for individuals under 45 years of age and 10.2 for individuals over 45 years of age. The IgG index, a dimensionless quotient for the determination of intrathecal IgG production, showed only a minor correlation with age and had an upper reference limit of 0.63. PMID- 8467820 TI - Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production. AB - To examine the possible influence of the blood-CSF barrier function on mathematical formulas for estimating intrathecal IgG production (IgG index, Tourtellotte's formula [TOURT], Schuller and Sagar's formula [Schull], and Reiber and Felgenhauer's formula [IgG(loc)]), we analysed serum and CSF samples from 105 healthy individuals, aged 18-88 years, and 816 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, aged 18-91 years. In healthy individuals there was no significant correlation between the CSF/serum (S) albumin ratio (i.e. blood-CSF barrier function) and the IgG index, a dimensionless quotient for determining intrathecal IgG production, and only a small correlation (r = -0.08, p < 0.05) in patients without OCBs. However, significant dependence on the blood CSF barrier function was found, in both healthy individuals and patients without OCBs, for the formulas determining intrathecal IgG production in milligrams (per litre CSF or per day), i.e. for TOURT, SCHULL and IgG(loc). Therefore, we propose a new formula for the quantitative determination of intrathecal IgG production in mg/l, the IGGPROD, which is calculated as: CSF-IgG -[(0.51 x CSF-Alb x S-IgG)/S Alb]. IGGPROD is an empirical formula, based on findings in 105 healthy individuals 18-88 years of age, and does not depend on the blood CSF barrier function. PMID- 8467821 TI - Dopamine receptor SPET imaging in Parkinson's disease: a [123I]-IBZM and [99mTc] HM-PAO study. AB - Single photon emission tomography (SPET) with the novel ligand [123I]-IBZM was used to image central dopamine D2 receptors in Parkinson's disease (PD) patients. The aim was to assess basal ganglia (BG) receptor densities in relation to the response to L-dopa therapy. To better characterize the clinical potential of [123I]-IBZM SPET, each patient underwent a second study with the regional perfusion tracer [99mTc]-HM-PAO. Tracer activity ratios were calculated for caudate and putamen with mean activity over the cerebellar hemispheres as internal standard. In PD patients we found a significant decline of mean caudate [123I]-IBZM activity, as compared with age-matched control subjects. However, when patients were grouped according to their therapeutic behavior, the [123I] IBZM uptake in BG ganglia regions of the PD patient group with a poor and fluctuating response to L-dopa was significantly reduced from mean values of patients with a sustained response to L-dopa therapy. [99mTc]-HM-PAO caudate and putamen uptake indexes in PD were similar to control values, even in patients with deteriorated therapeutic response. Our results indicate that BG D2 receptor alterations in PD may contribute to the altered response to L-dopa. PMID- 8467822 TI - Incidence of nervous system Borrelia burgdorferi infection in patients with lumboradicular syndrome. AB - We investigated 103 consecutive patients primarily admitted to our Department of Neurosurgery (36 women, age: median 44, range 21-79; 67 men, age: 47, range 19 77) suffering from low back pain radiating into one or both legs. Neurological examination combined with computer tomography and lumbar myelography revealed lumbar-disc herniation in 74, vertebrostenosis in 10 and relapsed disc herniation in 9 patients. In 9 patients the diagnosis of pseudoradicular syndrome was established without definite neuroradiological morphological evidence. Two patients were diagnosed as having polyneuropathy, and 1 patient suffered from a nervus ischiadicus lesion due to a gluteal abscess. CSF of all patients was examined according to a fixed routine schedule (cells, protein, sugar, immunoglobulins, IgG index). Antibodies to Borrelia burgdorferi were found in the serum and CSF of 5.8%, and in the serum alone of 2% of patients. Intrathecally produced specific antibodies were detected in 3 patients (2.9%) with neuroradiological evidence of disc or spinal-canal disease, indicating the coexistence of previous CNS infection by B. burgdorferi with lumbar-disc herniation. None of the patients showed CSF pleocytosis; thus, in no case was acute radiculitis due to B. burgdorferi infection diagnosed. PMID- 8467823 TI - Markers of activated T lymphocytes and T cell receptor gamma/delta+ in patients with multiple sclerosis. AB - We studied interferon-gamma (IFN-gamma), alpha-tumor necrosis factor (alpha-TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cerebrospinal fluid and serum of 18 patients with multiple sclerosis (MS) and 10 subjects with other neurological diseases (OND). We also studied the cerebrospinal-fluid CD 69 expression, and T cells with T cell receptor (TcR) gamma/delta+. We found an increase of IFN-gamma (14.0 +/- 3.5 U/ml) and GM-CSF (8.0 +/- 3.4 pg/ml) levels in the cerebrospinal fluid of MS patients compared to the OND group (p < 0.005 and p < 0.01, respectively). The frequency of detectable cerebrospinal-fluid and serum alpha-TNF was similar in patients with MS and with OND. The cerebrospinal-fluid CD69 expression in lymphocytes was significantly higher in MS patients (15.0 +/- 9.9%) than in the control group (3.7 +/- 6.2%; p < 0.005). Comparable serum levels of IFN-gamma and GM-CSF were detected in patients with MS and in OND subjects. No significant difference in the incidence of TcR gamma/delta+ in the cerebrospinal fluid was found between the two groups. These results indicate an activation of T lymphocytes and macrophages in patients with MS. Our data do not suggest a role for an increased incidence of TcR gamma/delta+. However, we cannot rule out the possibility that these T cells could be present at the plaque site of MS patients. PMID- 8467824 TI - Guillain-Barre syndrome after herpes zoster infection: a report of 2 cases. AB - We report 2 patients with Guillain-Barre syndrome following infection with the varicella-zoster virus. Evidence from neurophysiological studies is provided and the literature is reviewed on the association between these conditions. PMID- 8467825 TI - Atypical manifestations of tuberculous meningitis. AB - We describe 2 patients with tuberculous meningitis who exhibited unusual changes of their cerebrospinal fluid (CSF) which led to confusion in their management. Patient 1 was a 25-year-old man who displayed persistent polymorphonuclear dominant pleocytosis in his CSF. Autopsy revealed marked hypoplasia of the thymus and T cell areas of the lymph nodes, consistent with the Nezelof syndrome, as well as disseminated tuberculosis. Patient 2 was a 39-year-old woman who demonstrated, during appropriate antituberculous chemotherapy, an atypical exacerbation consisting of prolonged fever, polymorphonuclear dominant pleocytosis in her CSF and multiple cerebral infarcts. The neurological abnormalities in the patient underwent marked improvement following oral prednisolone therapy. PMID- 8467826 TI - Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime. AB - The regional cerebral blood flow (rCBF) in 19 patients with multiple sclerosis (MS), 10 with a relapsing remitting course and 9 with a progressive course, was examined by single photon emission computed tomography (SPECT) using technetium 99m hexamethylpropyleneamine oxime ([99mTc]-d,l-HM-PAO) as flow tracer. Nine age matched volunteers served as controls. Low rCBF in the frontal grey matter correlated with neurological disability (p < 0.01), low frontal grey and white matter perfusion correlated with impaired cognitive functions (p < 0.02), and low rCBF in the occipital regions correlated with impaired visual functions (p < 0.03) in the MS population. A relationship was also found between reduced parietal white matter perfusion and the duration of the disease (p < 0.005). Patients with progressive MS had significantly reduced rCBF in the frontal grey matter compared with relapsing remitting MS patients and controls (p < 0.05). No other rCBF differences were found. As a diagnostic tool in MS, SPECT-[99mTc]-d,l HM-PAO was found to be insensitive. PMID- 8467827 TI - Bezafibrate-induced myopathy: no evidence for defects in muscle metabolism. AB - A 58-year-old man with chronic renal failure developed severe muscle pain and tenderness 1 week after starting bezafibrate 400 mg daily. Serum creatine kinase was 32,280 U/l. Muscle biopsy revealed scattered necrotic fibers and mild type 2b atrophy. Muscle total and free carnitine were at the upper limits of the normal range. Biochemical investigations of muscle homogenate showed normal carnitine pelmityl transferase (CPT) as well as normal individual glycolytic and mitochondrial enzyme activities. Withdrawal of the drug was followed by rapid clinical improvement. Our study casts doubt on the hypothesis that bezafibrate is able to affect muscle metabolic pathways. It is likely that the drug acts on cholesterol constituents of the muscle membrane, producing discontinuities of the sarcolemma and initiating cell necrosis. PMID- 8467828 TI - Decreased interhemispheric EEG coherence during sleep in agenesis of the corpus callosum. AB - Inter- and intrahemispheric EEG coherence was studied in 4 subjects with agenesis of the corpus callosum (ACC) and in 4 matched controls through different states of the sleep/wakefulness cycle. Interhemispheric coherence was calculated between homologous prefrontal, frontal, central, parietal and occipital electrode pairs whereas intrahemispheric coherence was calculated between all adjacent, unihemispheric electrode pairs. EEG samples were recorded from stage 2, stages 3 + 4 and stage REM sleep and the eyes closed waking state. Interhemispheric coherence measures indicated lower values for ACC subjects than for control subjects for most brain regions; the occipital cortex was least affected. These results further validate the interhemispheric coherence function as a measure of activity in the corpus callosum and suggest that occipital measures may index activity localized in the posterior commissure. Intrahemispheric coherence measures indicated very few differences between the two groups, a result consistent with the suggestion that there is no specialized intrahemispheric compensation in ACC. PMID- 8467829 TI - Successful nonoperative treatment of tuberculous spinal epidural abscess with cord compression: the role of magnetic resonance imaging. AB - A patient is described with a tuberculous spinal epidural abscess and signs of cord compression, who was successful treated without surgery. Magnetic resonance imaging, in addition to its role as a diagnostic tool, was helpful in monitoring the resolution of inflammation. PMID- 8467830 TI - Left tuberothalamic artery territory infarction: neuropsychological and MRI features. AB - We examined a 29-year-old woman who had language disturbances and memory impairment after a left thalamic infarction. MRI showed injury that was limited to the tuberothalamic artery territory. Beside reduced voice volume and verbal memory trouble, she presented with aspontaneity, loss of psychic self-activation and affective drive. Considering thalamic lesions, this loss of psychic self activation or 'athymhormie' was found in a left thalamic infarct and could not be considered as an exclusive characteristic of bithalamic infarctions. The disappearance of the neurobehavioral disturbances within 15 days after the onset of the troubles was associated with the decreasing of the mass lesion found by MRI. PMID- 8467831 TI - Retinal periphlebitis in multiple sclerosis: a marker of disease activity? AB - This study was performed in order to verify the prevalence of retinal periphlebitis and other ocular changes in a well-defined population of multiple sclerosis (MS) patients, and to correlate the presence of these features with some clinical variables which characterize the disease. 110 MS-affected subjects were submitted to a standard ophthalmologic examination including a biomicroscopical evaluation of the fundus oculi. The prevalence of retinal sheathing in MS patients was found to be nearly 36%. It is significantly higher in patients evaluated in an active phase of the disease than in those examined in a stationary phase. PMID- 8467832 TI - Dynamic strength in Parkinson's disease. Quantitative measurements following withdrawal of medication. AB - This study examined the influence of pharmacological treatment on muscle strength in Parkinson's disease (PD). Twelve patients, 7 men and 5 women, were tested with modified Cybex II equipment. Peak torques in isometric, concentric and eccentric contraction at 30, 120 and 180 degrees/s in ankle dorsiflexors were recorded before and after the withdrawal of medication. EMG were recorded during contraction. Clinical assessment was done according to Webster's and Hoehn and Yahr's rating scales. Clinical scores were significantly increased (p < 0.05). Peak torques in isometric, concentric and eccentric contraction (p < 0.05) decreased at almost all velocities after withdrawal of medication. Correlations were found between changes in clinical score and strength. Strength production in PD was influenced by medication, and the results correlated with changes in clinical ratings. Strength measurement may be used in the evaluation of pharmacological therapy. PMID- 8467833 TI - Ophthalmoplegia, hemiparesis and cheiro-oral syndrome in basilar artery migraine. AB - A patient with migraine developed ophthalmoplegia, hemiparesis and cheiro-oral syndrome on the left side. T2-weighted MRI showed infarcts in the tegmentum of bilateral midbrains and right pons but no lesion in the cerebral or cerebellar hemisphere. Infarction in the tegmentum of brainstem secondary to the involvement of perforating arteries has not been reported in basilar artery migraine until now. PMID- 8467834 TI - Clinically asymptomatic xeroderma pigmentosum neurological disease in an adult: evidence for a neurodegeneration in later life caused by defective DNA repair. AB - Xeroderma pigmentosum is a genetically heterogeneous disease caused by DNA repair defects resulting in skin cancer and, in some patients, a primary neuronal degeneration which has in all previous reports become symptomatic prior to age 21 years. A 47-year-old xeroderma pigmentosum patient is described who, although neurologically asymptomatic, has sensorineural hearing loss together with clinical signs and electrophysiologic evidence of a developing peripheral neuropathy. This case suggests that defective DNA repair may cause neurodegeneration in adults as well as in children. PMID- 8467835 TI - Benign intracranial hypertension associated with HIV infection. AB - We report the case of a 24-year-old woman with HIV-seropositivity, who developed a clinical picture of pseudotumor cerebri, an association not previously described. The patient improved with the use of acetazolamide. We suggest the possible existence of this disorder in HIV-infected patients with persistent headaches, visual deficits and/or extraocular muscle palsies. PMID- 8467836 TI - Bilateral neuropsychological deficits in unilateral paramedian thalamic infarction. AB - The neuropsychological deficits in 5 patients with chronic and MRI-proven unilateral infarctions in the perfusion territory of the paramedian thalamic arteries were studied. All patients showed deficits pointing to a dysfunction of frontotemporal hemispheric structures on the side of the thalamic lesion. However, 4 patients revealed additionally neuropsychological deficits pointing to a dysfunction of frontotemporal hemispheric structures overlying the nonaffected thalamus. The contralateral deficits showed (in 4 patients) signs of temporal and (in 3 patients) frontal lobe dysfunction. It is suggested that the bilaterality of the neuropsychological deficits results from additional contralateral thalamic lesions not detected by MRI and/or from bilateral cortical hypometabolism. PMID- 8467837 TI - Effectiveness of botulinum toxin in the treatment of spasmodic torticollis. AB - Thirty-two patients with spasmodic torticollis were assessed quantitatively for posture deformity, tremor and range of neck movement, and qualitatively for pain and global subjective disability. All patients were then treated with intramuscular botulinum toxin injections into appropriate neck muscles. Fifty three treatments were administered using dosages of toxin in the range of 50-100 U per muscle. The maximum dose administered at a single sitting was 280 U. The progress of the patients was assessed during an 18-month period. Seventy-five percent of patients showed documented improvement in both subjective and objective parameters and were considered treatment successes. Pain improved in 65%, posture in 65%, tremor in 50% and range in 46%. The side effects that occurred were transient and included fatigue, dysphagia, neck weakness, hoarseness and local pain. This study demonstrates that treatment with botulinum toxin is of significant benefit for the majority of patients with spasmodic torticollis. PMID- 8467838 TI - Glycogenosis type V (McArdle's disease) with hyperuricemia. A case report and clinical investigation. AB - A 28-year-old male with glycogenosis type V associated with continuous hyperuricemia during mild daily activities is reported. An aerobic exercise test using a bicycle ergometer revealed that purine metabolites, i.e., ammonia, inosine, hypoxanthine and xanthine, were transiently increased by the exercise and that a subsequent increment in uric acid continued until the following day. The accelerated purine degradation by the muscle exercise was thus shown to be able to cause the overt hyperuricemia in a patient with glycogenosis type V. Therapeutic use of fructose for glycogenosis was disappointing due to fructose induced hyperuricemia. A search for myogenic hyperuricemia is essential for therapeutic trials. PMID- 8467839 TI - Clinical spectrum of McArdle disease: three cases with unusual expression. AB - Three cases of myophosphorylase deficiency with unusual clinical expression are presented. The 1st had clinical characteristics suggesting a mild congenital myopathy, and the patient never experienced cramps or myalgias. The 2nd had a slowly progressive myopathy without cramps or myoglobinuria which was detected by chance. The 3rd presented with myoglobinuria and acute renal failure, unrelated to a triggering effort, and with permanent weakness and wasting. In all cases, muscle biopsy demonstrated a vacuolar myopathy with free glycogen increase and absence of myophosphorylase activity, confirmed by biochemical assays. The cases confirm the wide clinical spectrum of McArdle disease. PMID- 8467840 TI - Rabies encephalitis mimicking the electrophysiological pattern of brain death. A case report. AB - A 48-year-old woman was referred from Zaire with suspected rabies encephalitis. Survival was 34 days after the onset of symptoms and the diagnosis of rabies was ultimately proven after brain autopsy. Serial neurophysiological investigations, including EEG and multimodality evoked potentials and radiological examinations (cerebral magnetic resonance imaging and computed tomodensitometry) were performed. Whereas the clinical findings and EEG were compatible with brain death at the end of the course, this diagnosis could be definitely ruled out by multimodality evoked potentials, magnetic resonance imaging and autopsy. The validity of multimodality evoked potentials is discussed in this particular setting. PMID- 8467841 TI - Trigeminal sensory symptoms due to midbrain lesions. AB - Three patients with midbrain lesion are described who showed trigeminal sensory symptoms in the contralateral side. Two with ischemic stroke showed partial oculomotor paresis while the third with probable vascular malformation had trochlear palsy. Considering their clinical manifestations and magnetic resonance findings, their sensory changes are believed to be caused by the involvement of the crossed trigeminothalamic fibers near the ocular motor nuclei. PMID- 8467842 TI - Is parkinsonian arm tremor a resting tremor? AB - Arm tremor in Parkinson's disease occurs during rest which has been explained by a specific tremulous mechanism activated during rest. During action or posture maintenance, the tremor may persist or recur, but with reduced amplitude. We present 2 patients with idiopathic Parkinson's disease who showed persisting arm tremor which was most marked during action rather than during rest. The patterns of upper limb tremor were investigated during rest, maintenance of fixed posture, and slow movement, using an advanced computerized movement-monitoring system (Coda 3). Four parkinsonian patients showing tremor under all conditions were studied, comparing 2 patients whose tremor was most marked during rest with 2 whose tremor was most marked during action. All showed intermediate amplitudes during posture maintenance. Patterns of tremor frequency were very similar between patients, irrespective of amplitude characteristics. These features suggest that tremors in all patients originate in a single, complex mechanism which may involve both central and peripheral mechanisms. PMID- 8467843 TI - Soluble class I antigen secretion by peripheral blood lymphocytes in multiple sclerosis. AB - We have quantified the soluble class I antigen (sHLA) secretion by peripheral blood lymphocytes of 26 multiple sclerosis (MS) patients. Thirteen of them were in a stable phase of the disease, 6 on relapse and 7 suffered from a progressive MS. sHLA secretion was reduced in the presence or absence of phytohemagglutinin in patients with either active or stable MS, being normal after stimulation with a monoclonal antibody anti-CD3. In MS patients, lymphocyte proliferation and immunoglobulin secretion were found to be similar to those of 29 healthy blood donors who comprised the group of controls. These results reflect systemic anomalies in the cell activation process in MS, which seem to be independent of the disease activity. Whether these alterations are specific to MS or are common to other inflammatory CNS diseases remains to be elucidated. PMID- 8467844 TI - Brain stem magnetic resonance imaging and evoked potential studies of symptomatic multiple sclerosis patients. AB - In this study we evaluated the sensitivity of neuroradiological and neurophysiological tests for detecting brain stem (BS) lesions in multiple sclerosis patients, since the recent introduction of the gradient motion rephasing technique has markedly increased the image quality of magnetic resonance imaging (MRI). From 50 MS patients (33 women and 17 men; mean age 35.9 +/- 8.3 years; mean duration of the disease 7.2 +/- 4.1 years) with clinical signs of BS involvement, brain MRI, BS auditory evoked potentials (BAEPs), and left and right median somatosensory evoked potentials (mSEPs) were obtained. BS MRI lesions were detected in 41 patients (82%); in 14 cases they were located in the medulla oblongata, in 55 in the pons, and in 24 in the midbrain. Single lesions were present in 20 patients, while two or more BS lesions were demonstrated in 21 patients; 30 patients had at least one lesion located close to the inner or the outer cerebrospinal fluid border. BAEPs were abnormal in 19 of the 50 patients (38%), and BS components of mSEPs were abnormal in 15 of 46 (33%). With combined use of these neurophysiological techniques, BS abnormalities were revealed in 24 patients (48%). Only 1 patient had neurophysiological BS abnormalities and normal MRI. Moreover, there was a good correlation (74%) between the clinical and MRI BS findings in the 23 patients with signs referable to focal neurological BS lesions. The concordances considering clinical and evoked potential reports were positive, but less marked.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467845 TI - Recurrent polyradiculoneuropathy with hyperthyroidism. AB - A 30-year-old woman, who had had two episodes of distal dominant sensorimotor disorders in the extremities, developed again sensorimotor involvement in the distal portion of all limbs. She was also found to have hyperhidrosis, tachycardia and goiter. Neurological and endocrinological examinations led to a diagnosis of coexistence of recurrent polyradiculoneuropathy and hyperthyroidism. Treatment with thiamazole resulted in improvement of the neurological features as well as of hyperthyroidism. The relationship between polyradiculoneuropathy and hyperthyroidism is discussed. PMID- 8467846 TI - Creutzfeldt-Jakob disease. Report of a case of the panencephalopathic type and experiences of a teaching hospital in Taiwan. AB - We report a case of the unusual panencephalopathic type of Creutzfeldt-Jakob disease (CJD) in Taiwan. This 59-year-old woman presented in 1983 with typical clinical manifestations of CJD and died 16 months later. Postmortem examination revealed severe neuronal loss, spongiosis and gliosis extensively in cerebral cortex and striatum as well as in the white matter. We also report 6 other CJD patients seen from 1983 to 1991 at Veterans General Hospital-Taipei. PMID- 8467847 TI - Persistent chorea after recurrent hypoglycemia. A case report. AB - In a 72-year-old woman with a 33-year history of diabetes mellitus bilateral chorea had occurred after a series of hypoglycemic comas at the age of 58. The choreiform movements remained untreated, persisted more than 10 years and inspite of intermittent exaggeration were tolerated by the patient. Except for the hyperkinetic movements, neurological examination of this patient was otherwise normal as was cranial computer tomography. PMID- 8467848 TI - Recurrent oligodendroglioma diagnosed with 11C-L-methionine and PET: a case report. AB - A benign oligodendroglioma was removed in a young patient who had temporal epileptic seizures. He then became free of any fit until 15 months after the operation, when he developed seizures progressively less controlled by therapy. All investigations were normal (including CT scan and MRI) except a PET study which showed a high uptake of 11C-L-methionine in the area of the previous tumor. The second operation revealed that this area was indeed a tumor recurrence. We briefly discuss the potential usefulness of PET for the follow-up of low grade gliomas. PMID- 8467849 TI - Elevated velocity of prostacyclin degradation in blood as a possible risk factor in patients with cerebrovascular disorders. AB - Blood and plasma from 193 patients at risk of cerebrovascular disorders and 87 patients with brain infarction were tested to study prostacyclin (PGI2) degradation. It has been reported that patients at risk for cerebrovascular disorders and especially with brain infarction have an enhanced velocity of PGI2 degradation. The increase in velocity was more marked in blood than in plasma. A direct relation between this enhancement and the manifestation of intravascular platelet activation was observed. These data suggest that elevated PGI2 degradation might be a risk factor for thromboembolic events in patients with cerebrovascular disorders. PMID- 8467850 TI - Increased density in the middle cerebral artery by nonenhanced computed tomography. Prognostic value in acute cerebral infarction. AB - In order to consider the prognostic value of hyperdensity of the middle cerebral artery (MCA), we studied retrospectively the medical records of 80 consecutive patients with the diagnosis of ischemic stroke who underwent a non-enhanced computed tomography no longer than 24 h after the onset of the symptoms. To determine the mortality and disability, a follow-up of 30 days was obtained. Mortality does not differ significantly in acute ischemic stroke patients with and without increased density of MCA. When disability, calculated with the Rankin scale, is considered, the two groups are different since patients with hyperdensity of the middle cerebral artery (MCA) have a significantly worse outcome. The two groups do not differ for age, sex, the presence of atrial fibrillation, hypertension, diabetes, myocardial infarction and/or angina, and these factors do not influence the prognosis being equally present in the dead and in the survivors. In the multivariate discriminant analysis with stepwise variable selection, the dense MCA sign was significantly correlated either to mortality or to disability, along with atrial fibrillation, age and diabetes. We conclude that the dense MCA sign can be a useful prognostic factor in the early phase of ischemic stroke. PMID- 8467851 TI - Moyamoya-like disease with inflammation. AB - A 29-year-old Caucasian male died from massive cerebral infarction due to unilateral occlusion of the terminal internal carotid artery. The carotid occlusion was secondary to subendothelial fibrous tissue proliferation which was associated with a considerable mononuclear cell infiltration of the carotid wall, characterised as T cells by immunoperoxidase methods. Angiography showed vascular network at the base of the brain compatible with Moyamoya disease. We suggest that the pathogenesis of Moyamoya-like disease in our patient involved a T-cell mediated attack to a vascular antigen. PMID- 8467852 TI - Hemorrhagic and ischemic cerebrovascular complications of active infective endocarditis of native valve. AB - Cerebrovascular events complicate the management of infective endocarditis. The purpose of this study is to analyze clinical features of cerebrovascular complications in infective endocarditis and to establish the appropriate time schedule of chemotherapy and cardiosurgical intervention. We studied the clinical data of 123 patients with active infective endocarditis of native valves retrospectively. Thirty-three patients (18 males and 15 females, age 17-57 years) had cerebrovascular complications such as cerebral ischemia (n = 22) or intracranial hemorrhage (n = 11). The majority of complications (21 ischemic and 13 hemorrhagic episodes) occurred prior to or within 1 month after chemotherapy. Fatal neurological deterioration developed after cardiac surgery in 2 patients. Both of them needed emergency cardiac surgery, because of worsening hemodynamic state, which was performed within 5 days after cerebral embolic events. The remaining patients undertaking cardiac surgery did all survive; in whom there were chemotherapeutic intervals of 11 days after ischemic events or of 23 days after hemorrhagic events. These medical records suggest that early cardiosurgical intervention, if necessary, needs at least 2-3 weeks of preceding chemotherapy. In cases undergoing more than 1 month of chemotherapy, cerebrovascular complications may be well managed by medical treatment alone. PMID- 8467853 TI - Development of palilalia after stereotaxic thalamotomy in Parkinson's disease. PMID- 8467854 TI - Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats. AB - The novel anticonvulsant drug ucb L059 ((S)-alpha-ethyl-2-oxo-1 pyrrolidineacetamide) was evaluated in several rodent models of partial and generalized seizures. Ucb L059 (27-108 mg/kg i.p.) increased the thresholds for tonic electroconvulsions and myoclonic and clonic seizures induced by timed i.v. infusion of pentylenetetrazol (PTZ), but was ineffective in the traditional maximal electroshock seizure and s.c. PTZ seizure tests in mice and rats in doses up to 500 mg/kg. The anticonvulsant potency of ucb L059 in seizure threshold tests was similar to that of standard drugs, such as valproate. In amygdala kindled rats, ucb L059 exerted potent anticonvulsant activity against both focal and secondarily generalized seizures at doses of 13-108 mg/kg. The adverse effects of ucb L059 were quantitated in the open field and in standard tests for motor impairment, such as the rotarod and chimney tests. Ucb L059 exerted only minimal effects on behaviour, e.g. slight hyperactivity, and did not impair muscle activity in the rotarod test in doses up to 1700 mg/kg i.p. The data indicate that ucb L059 is an interesting new anticonvulsant agent with a broad spectrum of activity and high therapeutic index. PMID- 8467855 TI - Inhibition of platelet-activating factor-induced leukocyte adhesion in vivo by a leumedin. AB - Leumedins are a class of amino acid derivatives which have been reported to exert anti-inflammatory properties through a mechanism related to their ability to inhibit the expression of adhesion molecules on leukocytes. In the present study, the ability of an orally active leumedin (NPC 17923) to inhibit leukocyte adherence stimulated by platelet-activating factor was examined using an in vivo intravital microscopy preparation of mesenteric venules in the rat. Oral pretreatment with NPC 17923 (100 mg/kg) markedly increased the ratio of white blood cell velocity to red blood cell velocity, indicating that less force was required to displace a white blood cell from the vascular endothelium. NPC 17923 also significantly inhibited the adherence of white blood cells to the endothelium during the superfusion with platelet-activating factor. While not significantly affecting vessel diameter under basal conditions, vessels were significantly larger in NPC 17923-pretreated rats during the superfusion with platelet-activating factor. These results are consistent with the hypothesis that the anti-inflammatory properties of leumedins are at least in part due to effects on leukocyte adherence, but may also be in part attributable to effects on vascular tone. PMID- 8467856 TI - Angiotensin II-induced tachyphylaxis in aortas of normo- and hypertensive rats: changes in receptor affinity. AB - Angiotensin II-induced tachyphylaxis was found to be associated with changes in agonist affinity (Ka) and EC50 values, as assessed by using Furchgott's equation derived for the determination of full agonist affinity. The diminished affinity during tachyphylaxis was observed in aorta ring preparations from both Wistar Kyoto and spontaneously hypertensive rats. Noradrenaline (10(-9) M) reduced the increase in the Ka value during tachyphylaxis in both strains. The results suggest that tachyphylaxis occurs at the level of the receptor, resulting in changes in the affinity of the ligand for the receptor and in the coupling efficiency of the receptor system. The results also support the probable role of modulators acting on allosteric receptor sites. PMID- 8467857 TI - Poststatin, a novel inhibitor of bradykinin-degrading enzymes in rat urine. AB - Incubation of bradykinin with rat urine resulted in the successive degradation of bradykinin to bradykinin-(1-8), bradykinin-(1-7) and bradykinin-(1-6). In contrast, in rat plasma, bradykinin was degraded via either bradykinin-(1-8) or bradykinin-(1-7) to bradykinin-(1-5). Phosphoramidon (1 mM) partially inhibited the degradation of bradykinin by rat urine, as well as the conversion of bradykinin-(1-7) to bradykinin-(1-6). D,L-2-Mercaptomethyl-3 guanidinoethylthiopropanoic acid (1 mM) and captopril (1 mM) did not have a significant effect on any of the degradation steps in rat urine. In contrast, all of the degradation steps in urine, namely, from bradykinin to bradykinin-(1-8), from bradykinin-(1-8) to bradykinin-(1-7) and from bradykinin-(1-7) to bradykinin (1-6), were markedly inhibited by poststatin (1 mM), even though this compound was reported originally to be a novel inhibitor of post-proline cleaving enzyme. Poststatin (1 mM) did not inhibit the degradation of bradykinin in rat plasma. These results indicate that poststatin is an effective inhibitor of kinin degrading enzyme in rat urine. PMID- 8467858 TI - Morphine and diffuse noxious inhibitory controls in the rat: effects of lesions of the rostral ventromedial medulla. AB - The aim of this study was to investigate whether the rostral ventromedial medulla (RVM) participates in the lifting of diffuse noxious inhibitory controls (DNIC) by systemic morphine. The effects of morphine (1 mg/kg i.v.) on DNIC were compared in sham-operated rats and animals with electrolytic lesions of the RVM performed one or three weeks earlier. The C-fibre-evoked responses of spinal dorsal horn convergent neurones were similar in the sham-operated and lesioned animals. DNIC acting on these responses were also similar in these groups. DNIC were similarly reduced naloxone reversibly following morphine injections in sham operated animals and animals tested one week after lesioning of the RVM. In contrast, DNIC were not significantly altered by morphine in animals tested three weeks after lesioning. The lesions were similar in both groups of animals. This time-dependent attenuation of the effects of morphine indicates that the RVM is not directly involved in the reduction of DNIC induced by systemic morphine. However, it is suggested that lesions in this region can induce a reorganization of brainstem opioidergic systems. PMID- 8467859 TI - Antidiuretic activity and release of factor VIII by vasopressin analogues. AB - Vasopressin and in particular its structural analogue dDAVP (1-deamino-8-D arginine vasopressin) can increase plasma concentrations of Factor VIII and tissue plasminogen activator (tPA) in some species of animals and in humans. For this reason dDAVP is used therapeutically in the treatment of bleeding episodes in patients suffering from haemophilia A and Von Willebrand's disease. However, the high antidiuretic activity of dDAVP constitutes and unwanted effect in this context. In the present study, a large number of analogues of vasopressin were designed, synthesized and tested in monkeys with the aim of producing compounds in which the Factor VIII-releasing activity was selectively isolated from the vasopressor and antidiuretic actions of the peptide. The results indicate that it is possible to separate these biological activities; however, none of the analogues tested so far possessed Factor VIII potencies comparable to that of dDAVP. PMID- 8467860 TI - Potentiation of dark onset feeding in obese mice (genotype ob/ob) following central injection of norepinephrine and clonidine. AB - Central monoaminergic neurotransmitters have been implicated in the control of food intake in different animal species but it remains unclear whether these same neurochemical systems effectively regulate feeding behaviour in the genetically obese (ob/ob) mouse. Neuropharmacological studies have demonstrated, for example, that microinjection of norepinephrine can elicit a reliable feeding response in the rat, particularly at dark onset. The present study was therefore designed to examine the impact of central injection of norepinephrine (20-160 nmol) and clonidine (5-80 nmol), an alpha 2-adrenoceptor agonist, on food intake in ob/ob mice and lean (+/?) controls. Presatiated obese and lean mice were injected with norepinephrine or clonidine immediately prior to the onset of the dark cycle. Food intake (kcal) was measured 1 h postinjection. Obese mice ingested more food than lean mice under baseline saline conditions. Injection of norepinephrine and clonidine increased eating in both phenotypes, although the ob/ob showed an enhanced feeding response to norepinephrine and clonidine administration. Intracerebroventricular pretreatment with the alpha 2-adrenoceptor antagonist yohimbine (12.5-50 nmol) significantly attenuated the increase in food intake observed in response to central injection of norepinephrine (40 nmol) and clonidine (10 nmol). However, the alpha 1-adrenoceptor antagonist corynanthine (15-60 nmol) or the beta-adrenoceptor antagonist propranolol (25-100 nmol) failed to alter noradrenergic feeding. These results suggest that modification of central alpha 2-noradrenergic function can alter natural feeding in mice, and that the ob/ob is particularly sensitive to this effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467861 TI - Catecholamine uptake inhibitors elevate 6-hydroxydopamine in brain after administration of 6-hydroxydopa. AB - Desipramine and nomifensine, two norepinephrine uptake blockers, elevated by 63 248% the levels of 6-hydroxydopamine found in the frontal cortex at 1-4 h after administration of 6-OH-DOPA. Nomifensine also elevated 6-hydroxydopamine by 83% in the striatum at 4 h. These results nullify prior suggestions in the literature that 6-OH-DOPA is decarboxylated to 6-hydroxydopamine mainly outside of catecholamine nerve terminals and that 6-hydroxydopamine subsequently gains access to nerve terminals via the axonal membrane transport system for catecholamines. PMID- 8467862 TI - Activation of neuropeptide Y1 and neuropeptide Y2 receptors by substituted and truncated neuropeptide Y analogs: identification of signal epitopes. AB - Neuropeptide Y (NPY-(1-36)) acts on Y1 and Y2 receptors at the sympathetic neuroeffector junction. Various truncated NPY analogs were tested in the isolated guinea-pig caval vein where NPY is a vasoconstrictor (Y1 receptors) and in isolated rat vas deferens, by monitoring the suppression of electrically evoked contractions (Y2 receptors). The aim of this study was to define which parts of the NPY-(1-36) molecule were required to activate these receptors. NPY-(1-36), [Pro34]NPY and [Glu16,Ser18,Ala22,Leu28,31]NPY (ESALL-NPY), the latter being an analog with increased alpha-helicity in the 14-31 region, evoked vasoconstriction with similar potency and efficacy. Cyclic as well as linear NPY analogs having the 4 to 7 N-terminal amino acid residues linked to the 9 to 19 C-terminal residues by an 8-aminooctanoic acid (Aoc) residue were 25-50 times less potent than NPY-(1-36) itself. In the cyclic analogs, a disulfide bond was introduced to bring the N- and C-termini close together. Linear Aoc-2-27-NPY was virtually inactive. The Y1 receptor needs an intact N-terminal end of NPY in order to become fully activated. The requirements for the C-terminus are less stringent, since substitutions in this part of the molecule resulted in fully active analogs. The central portion of the molecule may impose steric constraints on the N- and C-terminal ends, thereby facilitating Y1 receptor activation, but it does not seem to be essential for receptor recognition. NPY-(2-36) and NPY-(5-36) were only slightly less potent than the parent molecule in suppressing electrically evoked twitches in the vas deferens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467863 TI - Effects of long-term d-fenfluramine treatment on energy metabolism in rats. AB - The effects of chronic intragastric administration of the anorectic agent d fenfluramine on energy metabolism and nutrient concentrations were investigated at rest and during swimming. Rats were provided with permanent cannulas for blood sampling and intragastric administration of d-fenfluramine or saline. Energy expenditure and nutrient and hormone concentrations were determined. Under baseline conditions, d-fenfluramine increased carbohydrate utilization (14.2 vs. 7.0 mg/kg.min) and decreased fat oxidation (2.8 vs. 5.5 mg/kg.min). Plasma free fatty acid concentration was decreased (0.29 vs. 0.55 mmol/l) and lactate and insulin concentrations were increased after d-fenfluramine treatment (0.64 vs. 0.37 mmol/l and 61 vs. 33 mU/l, respectively). The shift in nutrient utilization also occurred during swimming. The exercise-induced increase in blood glucose was reduced after d-fenfluramine (+0.8 vs. +2.0 mmol/l). During swimming, free fatty acid, lactate and insulin concentrations were similar in the two groups. It is hypothesized that chronic d-fenfluramine treatment increases in the oxidation of carbohydrates and decreases the oxidation of fat as a result of a decrease in the transport of fatty acids over the mitochondrial membrane. PMID- 8467864 TI - Inhibition of cytokine production and endothelial expression of adhesion antigens by 5'-methylthioadenosine. AB - We investigated the activity of endogenous nucleoside 5'-deoxy-5' methylthioadenosine (MTA) on both the production of inflammatory cytokines and the cytokine-dependent endothelial expression of adhesion molecules. The compound inhibited the production of tumor necrosis factor (but not interleukin-1) in lipopolysaccharide-activated macrophages. In addition, MTA selectively inhibited the expression of intercellular adhesion molecule-1 in endothelial cells activated with interleukin-1. This effect was paralleled by a reduction in endothelial adhesiveness for polymorphonuclear leukocytes. These data suggest that MTA might have anti-inflammatory activity. PMID- 8467865 TI - Delayed administration of basic fibroblast growth factor protects against N methyl-D-aspartate neurotoxicity in neonatal rats. AB - Neuroprotective effects of basic fibroblast growth factor (bFGF) (200 mu/kg i.p.) were examined at different time points following intrastriatal injection of N methyl-D-aspartate (NMDA) in seven-day-old rats. When administered 0.5 h before intrastriatal NMDA injection, 200 micrograms/kg of bFGF significantly reduced NMDA-induced lesion by 47% as compared with vehicle treatment. Posttreatment with the same dose of bFGF at 0, 0.5 or 1 h after NMDA injection also significantly reduced those lesions by 45, 35 or 26%, respectively, while no neuroprotective effects was observed when administered at 2 or 4 h after NMDA injection. PMID- 8467866 TI - Opposite effects of mesencephalic microinjections of cholecystokinin octapeptide and neurotensin-(1-13) on brain stimulation reward. AB - Changes in operant responding for brain stimulation reward were studied before and after a microinjection of 1 nmol of sulphated cholecystokinin octapeptide, neurotensin or saline into the ventral tegmental area. Neurotensin produced a significant and long lasting decrease in the stimulation frequency required to produce a half-maximal rate of responding; cholecystokinin had the opposite effect, attenuating the rewarding efficacy the stimulation during the first 30 min post-injection. It is suggested that the opposite effects of the peptides on reward are due to their differential modulatory effects on a subpopulation of mesencephalic dopamine neurones. PMID- 8467867 TI - Testosterone is required for the stimulatory effects of 8-OH-DPAT on sexual behavior in castrated male rats. AB - The stimulatory effects of 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) on male sexual behavior in the absence and presence of testosterone were investigated. Male rats (n = 12) were castrated and tested for sexual behavior (15 min, with an estrous female) up to 1 year after castration. Castration caused an abrupt decrease (50%) in the number of intromissions before first ejaculation, and the number remained stable for about 8 weeks. Between 8-12 weeks after castration, when ejaculation frequency was low, 0.2 or 0.4 mg/kg 8-OH-DPAT had no effect on ejaculation frequency, but significantly decreased the number of intromissions before first ejaculation. In weeks 17-18 after castration, 0.4 mg/kg 8-OH-DPAT no longer affected copulatory behavior. A 5-mm testosterone filled Silastic capsule (implanted at week 19 after castration) resulted in subnormal plasma testosterone levels (mean 4.4 nmol/l) and did not fully restore male copulatory behavior. Administration of 8-OH-DPAT (0.2 and 0.4 mg/kg) was followed by an increase in ejaculation frequency and a decrease in ejaculation latency. Five months later, when plasma testosterone levels were very low (mean 0.6 nmol/l), 8-OH-DPAT (0.4 mg/kg) significantly increased the mean number of intromissions and ejaculations and decreased the number of intromissions before first ejaculation, intromission latency and ejaculation latency (borderline). The present results suggest that testosterone is required for the activating effects of 8-OH-DPAT on sexual behavior in castrated male rats, tested 17-52 weeks after castration. PMID- 8467868 TI - Activation of the ATP-sensitive K+ channel by decavanadate in guinea-pig ventricular myocytes. AB - To evaluate the effects of decavanadate on the ATP-sensitive K+ (KATP) channel, we applied the inside-out membrane patch-clamp technique to ventricular myocytes isolated from guinea-pig hearts. Decavanadate increased the probability of the KATP channel being open in a dose-dependent manner over the range of 0.1 to 5 mM in the presence of 0.3 mM ATP. Half-maximal activation occurred at 540 microM decavanadate and a Hill coefficient of 1.3 was obtained when the Hill equation was used to fit the dose-dependent activation for the channel by decavanadate. The half-maximum inhibition for the channel by ATP (K1/2) in the presence of 2 mM Mg2+ was 19 and 74 microM in its absence. In the presence of decavanadate, both curves shifted toward the higher concentration of ATP without a change in steepness of the slope (Hill coefficient = 2). The effect of decavanadate could be expressed by a model in which its binding prevents ATP binding from closing the channel. The estimated dissociation constant of decavanadate was 1.5 microM in the presence and 22.8 microM in the absence of Mg2+. Decavanadate reactivated the rundown channel in the absence of Mg2+ and ATP. Neither the single channel slope conductance nor the mean open and closed lifetime within the bursts of channel openings were affected by decavanadate. We conclude that internal Mg2+ is not required for the modulation produced by decavanadate, but this ion influences the channel and changes the dissociation constant of both ATP and decavanadate to the channel. PMID- 8467869 TI - Role of prostacyclin in acetylcholine release from myenteric plexus of guinea-pig ileum. AB - The roles of metabolites of arachidonic acid in spontaneous and agonist-induced acetylcholine release from a longitudinal muscle preparation with myenteric plexus of guinea-pig ileum were studied. Indomethacin significantly decreased both spontaneous acetylcholine release and its release induced by nicotine and substance P. We had found that prostaglandin E2 (PGE2) partly reversed this inhibition. We now found that a stable prostacyclin analog, OP-41483 at 100 nM, completely reversed the inhibition of acetylcholine release by indomethacin. On the other hand, PGD2, PGF2 alpha and ONO-11113, a thromboxane A2 analog, did not have any significant effect on the inhibition by indomethacin. OP-41483 had no effect on acetylcholine release induced by nicotine or substance P in the absence of indomethacin. To confirm the modulatory role of endogenous prostaglandins on acetylcholine release, we also studied the release of 6-keto-PGF1 alpha, a metabolite of prostacyclin, and PGE2 from longitudinal muscle preparations. The preparations released appreciable amounts of 6-keto-PGF1 alpha continuously during the experiments. Indomethacin inhibited release, while nicotine did not affect it so significantly. Our results suggest that endogenous prostacyclin modulates acetylcholine release from cholinergic nerve terminals in the myenteric plexus of guinea-pig ileum. PMID- 8467870 TI - Big endothelin-1 and big endothelin-3 are constrictor agents in the microvasculature: evidence for the local phosphoramidon-sensitive conversion of big endothelin-1. AB - The effect of local administration of big endothelin-1 (1-38, big ET-1) has been investigated on blood flow in the skin of anaesthetised rats, measured by 133Xe clearance. The local effects of big ET-1 and big endothelin-3 (1-41, big ET-3) have also been determined on microvessel diameter by intravital microscopy of the cheek pouch of anaesthetised hamsters. Big ET-1 (i.d.) caused a dose-dependent decrease in skin blood flow and was 10 times less potent than endothelin-1 (ET 1). Phosphoramidon (30 nmol/site i.d.) did not effect blood flow but when coinjected selectively attenuated the effect of big ET-1 (1 and 3 pmol/site, P < 0.05). In the cheek pouch big ET-1 (100 pmol) induced an intense and long-lasting arteriolar constriction. Phosphoramidon (100 nmol) abolished constriction to big ET-1 (100 pmol) but not to ET-1 (10 pmol). The modest constriction induced by big ET-3 (300 pmol) was not inhibited by phosphoramidon (100 nmol). Results suggest that a phosphoramidon-sensitive endothelin-converting enzyme situated close to microvascular vessels is important in the conversion of big ET-1. The mechanism for activity of big ET-3 in the microcirculation is unclear. PMID- 8467871 TI - The sigma receptor ligand 1,3-di-(2-tolyl)guanidine in animal models of schizophrenia. AB - The behavioral effects of the selective sigma ligand 1,3-di(2-tolyl)guanidine (DTG) were studied in rats. In the radial 8-arm maze, DTG (2, 4 and 8 mg/kg i.p.) reduced the number of arm entries in the spontaneous alternation task. In animals receiving 4 mg/kg DTG, the percentage of 135 degrees angles between consecutive arm entries decreased. In the open field, equipped with a holeboard, DTG (8 mg/kg) reduced the number of line crossings, rearings and head dips. Sniffing, measured in an experimental chamber, was also reduced. DTG prolonged the time that the animals were inactive. In combination with DL-amphetamine (4 mg/kg) or dizocilpine (0.16 mg/kg), DTG (8 mg/kg) decreased--but did not antagonize--the induced enhancement of locomotion and sniffing. These results demonstrate motor depressant effects of DTG on locomotion, rearing and sniffing. Since antagonists of sigma binding sites are known to produce opposite effects, we conclude that DTG--in behavioral terms--acts like an antagonist at sigma binding sites. PMID- 8467872 TI - Effects of the Ca2+ chelators EGTA and EDTA on ethanol- or stress-induced gastric mucosal lesions and gastric secretion. AB - Ca2+ modulates gastric function and dysfunction as well as the release of cysteine proteases and metalloproteinases which have been implicated in the pathogenesis of gastric mucosal lesions. We thus tested the hypothesis that pretreatment with the Ca2+ chelators, ethylene diamine tetraacetic acid (EDTA) and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) might reduce the experimental gastric mucosal damage induced by restraint cold stress or 1.0 ml of 75% ethanol. Other rats were prepared with chronic indwelling gastric cannulas and the effects of EDTA and EGTA on conscious basal gastric acid output were assessed. In addition, rats were pretreated with EGTA or EDTA prior to pylorus ligation and their effects on acid and pepsin output assessed. Both EDTA and EGTA reduced significantly the extent of ethanol-induced gastric mucosal damage as well as the degree of stress-induced gastric lesions. To further characterize the mechanism of Ca2+ chelator protection against ethanol-induced gastric lesions, some rats were vagotomized or adrenalectomized prior to treatment with EGTA or EDTA, followed by ethanol or stress. Both adrenalectomy and vagotomy abolished gastroprotection by EGTA and slightly reduced that induced by EDTA in both models of experimental gastric mucosal injury. Both EDTA and EGTA reduced significantly basal gastric acid output, an effect which persisted for at least 2 h following their administration. Both compounds also decreased significantly acid and pepsin output in pylorus-ligated rats. We conclude that Ca2+ chelators attenuate both acid-dependent and acid-independent gastric lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467873 TI - Suppression by ethanol of pressor response caused by the inhibition of nitric oxide synthesis. AB - The effects of ethanol on mean arterial pressure (MAP) and heart rate (HR) responses to the nitric oxide synthase inhibitor, NG-nitro-L-arginine, and to angiotensin II and noradrenaline were studied in rats. I.V. bolus injections of NG-nitro-L-arginine dose dependently increased MAP in vehicle-pretreated rats, with a maximum increase of 56 +/- 7 mm Hg and an ED50 of 3.8 +/- 0.4 mg/kg, respectively. I.v. infusions of ethanol dose dependently reduced maximum MAP response to NG-nitro-L-arginine, with a Ki of 96 +/- 8 mg/kg per min but did not alter the ED50. Ethanol (48 mg/kg per min) did not modify the MAP response to i.v. bolus injections of angiotensin II (0.02-1.28 micrograms/kg) or noradrenaline (0.25-16 micrograms/kg). However, ethanol attenuated the reflex HR responses of NG-nitro-L-arginine and angiotensin II but not that of noradrenaline. The results demonstrate that ethanol selectively but non competitively inhibits the MAP response to NG-nitro-L-arginine, suggesting an interaction between ethanol and the L-arginine/nitric oxide pathway. PMID- 8467874 TI - The interaction of selective and non-selective antagonists with pre- and postjunctional muscarinic receptor subtypes in the guinea pig trachea. AB - Muscarinic receptor antagonists were used to study prejunctional M2 and postjunctional M3 receptors in the isolated guinea pig trachea. The effects of four M2-selective muscarinic receptor antagonists (gallamine, methoctramine, AQ RA 741 and AF-DX 116) were studied on twitch contractions, elicited by electrical field stimulation, of tracheal ring preparations. M1-selective (pirenzepine, (+)- and (-)-telenzepine), M3-selective (4-DAMP-methobromide and UH-AH 371) and non selective (atropine and ipratropium) muscarinic receptor antagonists were also used. The clear potentiation of the twitch contractions and the subsequent strong inhibition observed with M2-selective antagonists demonstrate antagonism at prejunctional M2 and postjunctional M3 muscarinic receptors, respectively. The maximal potentiation correlated well with the M2/M3-selectivity known from binding experiments: gallamine > methoctramine > AQ-RA 741 > AF-DX 116. Strong correlations were also found between the pEC20 values for potentiation of the twitch response and the pKi values for bovine cardiac M2 muscarinic receptors and between the pIC50 values for inhibition of the twitch response and the pA2 values for M3 muscarinic receptors as determined on non-stimulated methacholine contracted tracheal smooth muscle preparations. Thus, study of the effects of a wide concentration range of putative M2-selective muscarinic receptor antagonists on the twitch contractions of single tracheal rings induced by low-intensity electrical field stimulation yields information about M2/M3 receptor selectivity and about prejunctional M2 and postjunctional M3 receptor affinity within the same experiment. PMID- 8467875 TI - Protective actions of 21-aminosteroids and MK-801 on hypoxia-induced electrophysiological changes in rat hippocampal slices. AB - The effects of the 21-aminosteroids, U-74500A and U-78517F (drugs endowed with lipid peroxidation inhibitor properties) were tested on hypoxia-induced functional failure in rat hippocampal slices. For comparison, the effects of the non-competitive N-methyl-D-aspartate antagonist, dizocilpine (MK-801) were studied. Perfusion of slices with 50 microM of MK-801 or with 50-100 microM of U 78517F, but not with 100-200 microM of U-74500A, significantly (P < 0.01) increased the incidence of reappearance of the CA1 population spikes after reoxygenation in rat hippocampal slices subjected to a 45-min hypoxic period followed by a 45-min reoxygenation period. Perfusion of slices with 12.5 microM of MK-801 plus 12.5 microM of U-78517F significantly (P < 0.05) increased the incidence of reappearance of the CA1 population spikes after reoxygenation with respect to perfusion of slices with 12.5 microM of U-78517F alone or with 12.5 microM of MK-801 alone. The results show that 21-aminosteroids have protective effects against hypoxia-induced functional failure in rat hippocampal slices. In addition, the data show that, under the same experimental conditions, the NMDA receptor antagonist, MK-801, was also able to improve hypoxia-induced functional failure. On the whole, the results suggest that the hypoxia-induced functional electrical failure might depend on both release of excitatory amino acids and oxygen free-radical-mediated membrane lipid peroxidation. PMID- 8467876 TI - The novel 5-HT4 receptor antagonist DAU 6285 antagonizes 5-hydroxytryptamine induced tachycardia in pigs. AB - The 5-HT4 receptor antagonist action of DAU 6285 was investigated in vivo in anesthetized pigs. DAU 6285 (0.3-3 mg/kg i.v.) dose dependently antagonized 5 hydroxytryptamine (5-HT)-induced tachycardiac responses. In contrast, the 5-HT3 receptor antagonist, ondansetron (0.3-3 mg/kg i.v.) did not influence the tachycardia induced by 5-HT. These results indicate that DAU 6285 is a potent antagonist of 5-HT4 receptor-mediated responses in vivo. PMID- 8467877 TI - Cyclosporine A induces endothelin-1 release from cultured rat vascular smooth muscle cells. AB - Since vascular smooth muscle cells in culture are capable of secreting endothelin 1 (ET-1), we investigated the effect of cyclosporine A on ET-1 release from rat vascular smooth muscle cells. Cyclosporine A 10 microM significantly (P < 0.05) enhanced the secretion of ET-1 at 2, 8, 24 and 48 h (6.5 +/- 0.5, 11 +/- 0.7, 19 +/- 0.5, 37 +/- 1.6 fmol/10(6) cells, respectively) compared with vehicle (4.7 +/ 0.3, 8.1 +/- 0.6, 15 +/- 0.4, 27 +/- 2.0 fmol/10(6) cells, respectively). The cyclosporine-induced synthesis of ET-1 by vascular smooth muscle cell may participate in the pathogenesis of cyclosporine-induced vasoconstriction and vasculopathy via an autocrine regulatory mechanism. PMID- 8467878 TI - Interleukin-1 alpha and tumour necrosis factor inhibit rat gastric fundus motility in vitro. AB - In this study, the effects of tumour necrosis factor (TNF) and interleukins 1 alpha and 6 (IL-1 alpha and IL-6) on rat gastric fundus motility were investigated in vitro. IL-1 alpha and TNF induced rapid dose-dependent inhibition of stomach motility, with maximal relaxation equal to that induced by 100 microM papaverin, and respective EC50s of 20 and 450 pg/ml. IL-6 had no effect on gastric motility up to a 3 ng/ml concentration. PMID- 8467879 TI - Disinhibition of hippocampal pyramidal cells during the transition into theta rhythm. AB - The activity of hippocampal complex-spike cells (presumed pyramidal cells) and theta cells (presumed interneurons) was examined during transitions from non theta electroencephalogram (EEG) states to theta EEG states in freely moving and sleeping rats. Theta cell firing rates were significantly depressed in a 1-s period centered on the EEG transition relative to the surrounding 1-s periods (normalized rates +/- SEM): 1.05 +/- 0.02 for the "non-theta" period, 0.59 +/- 0.03 for the "transition" period, and 1.36 +/- 0.04 for the "theta" period (n = 26 cells). Conversely, complex-spike cell firing was significantly increased during the transition period: 0.51 +/- 0.11 for the "non-theta" period, 2.24 +/- 0.19 for the "transition" period, and 0.24 +/- 0.04 for the "theta" period (n = 27 cells). This diametrically altered activity indicates that theta cells must be actively inhibited during the transition. The increased activity in complex-spike cells during the transition may be simply a release from inhibitory control by interneurons. The pattern of theta cell inhibition together with increased complex-spike cell activity appears to be a general property of transitions into the theta EEG state, irrespective of behavior. It is suggested that increased activity in septal afferents (GA-BAergic cell activity greater than cholinergic cell activity) initially inhibits hippocampal interneurons. The inhibition is not sustained because of an activity-dependent decrease in the potency of the septointerneuronal inhibition, leaving the rhythmic excitatory (cholinergic) septointerneuronal inputs, together with principal cell inputs, to increase interneuron firing rates. PMID- 8467881 TI - Motion sensitive cells in the macaque superior temporal polysensory area. I. Lack of response to the sight of the animal's own limb movement. AB - An animal's own behaviour can give rise to sensory stimulation that is very similar to stimulation of completely external origin. Much of this self-induced stimulation has little informative value to the animal and may even interfere with the processing of externally induced stimulation. We have measured responses of visual movement sensitive neurons in the anterior part of the dorsal superior temporal sulcus of monkeys to stimulation caused by the animal's own active movements. These cells responded to any stimuli moved by the experimenter, but gave no response to the sight of animal's own limb movements. The cells remained responsive to external stimulation, however, while the monkey's own hand was moving in view. Responses to self-induced movements were recovered if the monkey introduced a novel object in its hand into view. Various possible neural mechanisms for explaining the results are discussed, and it is suggested that the studied neurons belong to a system that detects unexpected and hence behaviourally relevant sensory events. PMID- 8467880 TI - The effect of fasciculus cuneatus lesions on finger positioning and long-latency reflexes in monkeys. AB - Previous studies have reported abnormalities in fine hand and finger movements following interruption of the fasciculus cuneatus (FC) in primates. We report here that many of these deficits could be caused by an inability to actively regulate the position of the finger. Three macaques were trained to maintain the index finger in one position against constant or changing loads. Periodically, torque pulses were used to elicit reflexes in finger muscles. Following unilateral FC lesions, the monkeys failed to adjust finger position during the trials, and the normal M2 long-latency response was absent in the finger muscles. Performance on the task was impaired only in monkeys with complete lesions that included the deep ventral portion of the FC. These results suggest that afferent fibers in the FC regulate finger position, and do so partly through reflexive mechanisms. When the FC is interrupted, the inability to control finger position disturbs fine motor activities. PMID- 8467882 TI - Gain and threshold of the jaw-jerk reflex in man during isometric contraction. AB - The control of mandibular posture has been related to the activity of the anterior temporal muscles, whereas the masseter muscles have been viewed mainly as force producers. However, these groups of muscles, especially in the deep layers, are highly endowed with muscle spindles, so that a difference in function should imply a difference in the reflex sensitivity. By studying the jaw-jerk reflex by means of bipolar surface electromyogram, the reflex sensitivity was determined from relationships between reflex amplitude and jaw displacement from both groups of muscles in eight subjects. At a constant level of background muscle activity, and hence with a constant excitability of the alpha motoneurons, the reflex sensitivity can be determined from these relationships in terms of gain and threshold. In order to account for differences in thickness of the soft tissues overlying the various muscles studied, the reflex amplitude was normalized with respect to the level of maximal voluntary contraction (MVC). In experiments where the inter-electrode distance was 18 mm over both groups of muscles, the reflex gain of the anterior temporal muscles was larger than that of the masseter muscles (P < 0.05). The threshold value did not differ significantly from zero for either group of muscles. Normalization of the reflex amplitude with respect to MVC can be carried out correctly only if the reflexly activated muscle fibres are distributed uniformly within the muscle. In order to gain an insight into this distribution, control experiments were performed with three subjects in which the inter-electrode distance was varied, thus influencing the depth in the muscle from which active muscle fibres were recorded. The reflex gain of the masseter muscle with an inter-electrode distance of 22 mm, which records from deeper layers of the muscle as well as superficial ones, was larger than with a distance of 11 mm (P < 0.01-0.10 in the various subjects). No such differences were found for the anterior temporal muscle. It was concluded that the afferents of the spindles in the jaw-elevator muscles do not project uniformly upon the motoneurons, but involve mainly fibres in the deeper layers of the muscle. The difference in gain found between the masseter and the anterior temporal muscles with the same inter-electrode distance of 18 mm is likely to be due to a larger distance of the reflexly activated muscle fibres in the masseter muscle with respect to the electrodes rather than to a difference in reflex sensitivity between the muscles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8467883 TI - Jaw-jerk reflex activity in relation to various clenching tasks in man. AB - In order to investigate whether the mandibular stretch (jaw-jerk) reflex is modulated in a task-dependent manner, jaw-jerk reflexes were elicited in eight subjects during clenching with unilateral and bilateral tooth support, respectively. The reflexes were examined in the electromyographic (EMG) activity recorded by means of surface electrodes and were elicited by means of small transient jaw displacements at a constant value of 80 microns. Low levels of background EMG were applied ranging from 1 to 30% maximal voluntary contraction (MVC) as controlled by means of visual feedback. Linear relationships were observed between reflex amplitude and level of background EMG. The slope in these relationships served as a measure of reflex gain. For the masseter as well as the anterior temporal muscles, the reflex gain, averaged over both sides, was larger during clenching with unilateral tooth support than with bilateral tooth support (P < 0.05). Furthermore, the gain was larger on the side without tooth support during unilateral clenching and larger on the side without visual feedback of elevator muscle activity during bilateral clenching. It can be concluded that the jaw-jerk reflex is modulated to subserve the stabilization of the mandible, with the reflex sensitivity being larger the more that alternative stabilizing factors such as mechanical tooth contact, visual feedback and feedback from periodontal pressure receptors around the teeth are lacking. The reflex modulation may be of functional importance in stabilizing the mandible during its movement in the chewing process, as the food is predominantly placed unilaterally between the antagonistic teeth during individual chewing cycles. PMID- 8467884 TI - The visual guidance of catching. AB - In order to explore the nature and amount of information in the optic array used by subjects required to carry out one-handed catching actions, the optical expansion pattern (using a deflating ball) and the duration of viewing time (using liquid crystal spectacles) of the ball were varied. Subjects were required to catch luminous balls (two of constant physical size and one of changing physical size during approach) attached to a pendulum in a totally dark room, while the liquid spectacles were closed at 0, 100, 200 or 300 ms before hand-ball contact. The results confirmed previous findings that the timing of the catching action is based on retinal expansion information and that conclusion was strengthened when an additional dependent variable (time of the maximal opening velocity of the grasp) was used. Further, for the viewing time duration manipulations, the time of the maximal closing velocity of the hand was later, while no effect was found on the time of the maximal opening velocity, when the last 300 ms of the trajectory of the ball was occluded. Adjustments to the catching action in response to the different ball sizes under the 0 ms condition differed significantly from the adjustments under the 300 ms condition. Both findings point to the importance of relative optical expansion information, available between 300 and 200 ms before ball-hand contact, in maintaining a (relatively) continuous perception-action coupling in the act of catching. PMID- 8467885 TI - Selective adaptation of internally triggered saccades made to visual targets. AB - We examined whether internally triggered saccades made to a nonjumping target (I saccades) could be adapted independently from externally triggered saccades induced by a jumping target (E-saccades). Five subjects made I-saccades between two fixed targets, one placed straight ahead and the other one positioned at an eccentricity of 17.5 degrees. The peripheral target was displaced to an eccentricity of 8.75 degrees during the saccadic movements toward this target. Amplitudes of the I-saccades made from the central to the peripheral target before and after adaptation were compared with each other. Saccadic amplitudes after adaptation were between 10% and 42% smaller than those before adaptation. E saccades induced by a single target which jumped from straight ahead to the same peripheral target position as was used for the I-saccades were also measured before and after the adaptation of I-saccades. Amplitudes of E-saccades before and after adaptation were hardly different from each other except in one subject. The mean decreases in amplitude of the two types of saccades, averaged over all subjects, were 21% for I-saccades and 5% for E-saccades. These results show that I-saccades can be adapted to changed visual conditions while E-saccades remain unadapted. We conclude from this finding that I-saccades and E-saccades are generated by at least partially different neural mechanisms. PMID- 8467886 TI - Common processing constraints for visuomotor and visual mental rotations. AB - Naive human subjects were tested in three different tasks: (1) a visuomotor mental rotation task, in which the subjects were instructed to move a cursor at a given angle from a stimulus direction; (2) a visual mental rotation task, in which the subjects had to decide whether a displayed letter was normal or mirror image regardless of its orientation in the plane of presentation; and (3) a visuomotor memory scanning task, in which a list of two to five stimuli directions were presented sequentially and then one of the stimuli (test stimulus), except the last one, was presented again. Subjects were instructed to move a cursor in the direction of the stimulus that followed the test stimulus in the previous sequence. The processing rate of each subject in each task was estimated using the linear relation between the response time and the angle (mental rotation tasks) or the list length (memory scanning task). We found that the processing rates in the mental rotation tasks were significantly correlated but that neither correlated significantly with the processing rate in the memory scanning task. These results suggest that visuomotor and visual mental rotations share common processing constraints that cannot be ascribed to general mental processing performances. PMID- 8467887 TI - Stimulation of human somatosensory cortex: tactile and body displacement perceptions in medial regions. AB - We examined the somatosensory perceptions evoked by stimulation of rolandic and parietal brain regions in 40 epileptic patients undergoing a presurgical investigation with intracerebral electrodes. Bipolar stimulation trains were delivered in an incremental sequence at medial and/or lateral contact pairs of stereotaxically implanted, multi-contact electrodes, while monitoring stimulus after discharge propagation with electrodes in frontal and temporal lobes. Rolandic stimulation evoked contralateral sensations, whereas sensations from either side were evoked in the opercular region. Stimulation of lateral posterior parietal cortex evoked only few sensations and these were restricted to the supramarginal gyrus. Contralateral sensations were evoked in the posterior cingulate gyrus, whereas ipsilateral sensations were evoked in the vicinity of the cingulate sulcus. Complex proprioceptive sensations in the form of bilateral feelings of levitation were elicited in a medial parietal region around the subparietal sulcus and not at any other site. These perceptions were not accompanied by any movement, tactile, or vestibular sensations, suggesting that the human sub-parietal sulcus region is linked to the proprioceptive processing system. PMID- 8467888 TI - Dependence of elbow viscoelastic behavior on speed and loading in voluntary movements. AB - The objective of this study was to characterize the mechanical behavior of the elbow joint during voluntary movement, for different speeds of movement and under different loading conditions. Torque pulses of 50 ms duration were applied at movement onset and at peak velocity on random trials. The displacement away from the unperturbed trajectory was used as an indicator of the relative compliance of the elbow under different conditions. We found that both the displacement and the time taken to return to the unperturbed trajectory decreased if the overall speed of the movement increased or if a viscous resistive load was added, implying lower joint compliance. It was possible to account qualitatively for differences in mechanical behavior from observed muscle activation patterns. PMID- 8467889 TI - Postexercise depression of motor evoked potentials: a measure of central nervous system fatigue. AB - Fatigue of voluntary muscular effort is a complex and multifaceted phenomenon. Fatigue of peripheral nervous system components, including the contractile apparatus and the neuromuscular junction, has been well studied. Central nervous system components also fatigue, but studies have lagged for want of objective methods. Transcranial magnetic stimulation is a relatively new technique that can be used to assess central nervous system excitability from the motor cortex to the alpha-motoneuron. In six normal volunteers, including four of the investigators, the amplitudes of motor evoked potentials elicited by transcranial magnetic stimulation were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The decrease in amplitude was associated with a feeling of fatigue. The mechanism of this phenomenon is apparently decreased efficiency in the generation of the motor command in the motor cortex. PMID- 8467890 TI - Fusimotor effects of midbrain stimulation on jaw muscle spindles of the anaesthetized cat. AB - The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine during sinusoidal or ramp-and-hold stretches. Changes in their stretch responses during midbrain stimulation were then assessed by changes in bias and in dynamic sensitivity. Problems were encountered in interpreting changes in sine wave stretch responses of primary afferents, in some of which a very small change in firing pattern produced large changes in estimates of the response amplitude. Sine wave testing also sometimes over-estimated static effects and under-estimated dynamic effects relative to ramp responses. On other occasions a small amount of static fusimotor activity caused a marked increase in sine response amplitude, which could be wrongly interpreted as a dynamic effect. Consequently, ramp responses only were used for diagnosing fusimotor changes. The most effective region for producing pure dynamic fusimotor excitation was directly rostral to the red nucleus, extending dorsally and ventrally approximately in the course of the retroflex bundle. Stimulation of regions caudal and dorso-caudal to the red nucleus, previously designated as the mesencephalic area for dynamic fusimotor control of leg muscles, gave static or mixed static and dynamic effects on jaw spindles. The use of midbrain stimulation to identify fusimotor neurones of jaw muscles as static or dynamic would be most reliable with stimulation just rostral to the red nucleus and would require spindle afferent behaviour to be monitored at the same time with ramp stretches. PMID- 8467891 TI - Behavioral state dependence of homo- and hetero-synaptic modulation of dentate gyrus excitability. AB - The effects of two different waking behavioral states on the modulation of perforant, path-evoked population spikes were studied following prestimulation of either the perforant path itself, the dentate gyrus commissural/association pathway, or the medial septum. The intermediate-latency, post-inhibitory 'rebound' of the population spike, which normally follows short-latency, perforant path or commissure-induced inhibition, was substantially increased during forced locomotion on a treadmill, compared with quiet wakefulness. There was no effect of these behavioral states either on the short-latency inhibitory phase itself or on the average magnitude of the unconditioned population spike. The short-latency, GABA-mediated disinhibitory effect of medial septal prestimulation was slightly reduced by walking, as might be expected from the increased feedforward excitatory drive on hippocampal interneurons that occurs during walking. Septal prestimulation during walking also led to a large, intermediate-latency spike facilitation that was completely absent during the quiet, awake state. Lesions of the medial septum attenuated the effects of behavioral state on the post-inhibitory facilitation from both perforant path and commissural stimulation. Atropine reduced the walking-induced increase in intermediate-latency facilitation, but had no effect in the still condition. We conclude that, during walking, electrical stimulation within the hippocampal formation or septum leads to a delayed increase in dentate gyrus excitability that is probably mediated polysynaptically through the medial septum or fibers passing through it. This state dependency is not due to tonic suppression of the inhibitory systems within the dentate gyrus itself. PMID- 8467892 TI - Orientation sensitive elements in the corticofugal influence on centre-surround interactions in the dorsal lateral geniculate nucleus. AB - In a previous study, we have shown that the corticofugal projection to the dLGN enhances inhibitory mechanisms underlying length tuning. This suggests that the inhibitory influences deriving from the corticofugal feedback should exhibit characteristics that reflect the response properties of orientation-tuned layer VI cells. Here we report data obtained from experiments using a bipartite visual stimulus, with an inner section over the dLGN cell receptive field centre and an outer section extending beyond it. For both X and Y cells there was a modulation of the strength of the surround antagonism of centre responses that was dependent on the orientation alignment of contours in the two components of the stimulus. Layer VI cells showed maximal responses when the two components were aligned to the same orientation; dLGN cells showed a minimal response. Varying the orientation alignment of the inner and outer components of the stimulus in a randomised, interleaved fashion showed that bringing the stimulus into alignment resulted in a 24.28% increase in the surround antagonism of the centre response. Blocking cortical activity showed this effect of alignment to be strongly dependent on corticofugal feedback. This effect of orientation alignment appears to apply for any absolute orientation of the alignment condition and supports the view that an entire subset of cortical orientation columns generate the feedback influencing any given dLGN cell. This mechanism makes dLGN cells sensitive to the orientation domain discontinuities in elongated contours moving across their receptive field. PMID- 8467893 TI - Critical timing of sensorimotor cortex lesions for the recovery of motor skills in the developing cat. AB - Forelimb movements and motor skills were studied in adult cats in order to determine the effect of brain damage inflicted at different postnatal ages. The unilateral lesion included the cortical areas from which the pyramidal tract originates in cat: areas 4 and 6 corresponding to the motor cortex; areas 3, 2 and 1 corresponding to the primary somatosensory cortex; and part of area 2 prae insularis corresponding to the secondary somatosensory cortex. Forelimb performance of a food-retrieving task requiring proximal as well as distal muscles was assessed by comparing the limb contralateral to the damaged hemisphere (affected limb) with the limb contralateral to the intact hemisphere (non-affected limb) that appeared to perform the task as well as both limbs of control animals. In simple task-related movements, all operated animals were rapidly able to achieve the goal with the affected limb, whatever the age at lesion. In complex tasks, the ability to achieve the goal with the affected limb decreased with increasing age at lesion. Recovery of distal skills, i.e. grasping and wrist rotation, did not occur in animals operated on after the 23rd postnatal day (PND), and recovery of proximal skills, i.e. amplitude and precision of the reaching movement, did not occur in animals operated on after the 45th PND. The critical time for the recovery of distal skills lies somewhere between the 23rd and 30th PND, whereas for the recovery of proximal skills it lies somewhere between the 45th and 60th PND. These critical dates for the recovery of motor skills support the Kennard doctrine. Different critical times for proximal and distal skills may be explained in terms of different stages of sensorimotor development in kitten. It is hypothesised that recovery only occurs if brain damage is inflicted before maturation of the nervous system underlying a given motor skill. PMID- 8467894 TI - Modulation of the development of light-initiated asymmetry in chick thalamofugal visual projections by oestradiol. AB - Thalamofugal visual projections of light-incubated chicks are organised asymmetrically. This asymmetry, which is generated by light stimulation of the embryo during the final days of incubation, is sexually dimorphic, being more pronounced in males than in females. We have shown that the development of the asymmetry can be prevented by elevating circulating levels of 17 beta-oestradiol in the embryo prior to hatching. Light-incubated male chicks were treated 5 days prior to hatching with either one of two doses of 17 beta-oestradiol (1.5 mg or 2.5 mg in a 0.1 ml solution of 10% ethanol in olive oil) or the vehicle only. After hatching the retrogradely labelling fluorescent dyes True Blue and Fluorogold were injected into the left and right side of the hyperstriatal region of the forebrain, consequently labelling the cell bodies of thalamic neurons which project to this region. Although a pronounced asymmetry was present in the control group, it was not present in both of the 17 beta-oestradiol-treated groups. These results suggest that the asymmetrical development of thalamofugal visual projections in response to lateralised light stimulation of the embryo is dependent on circulating levels of steroid hormones, and that compared to the male, the lesser degree of asymmetry found in thalamofugal projections of untreated females may be related to the higher levels of circulating oestradiol present in females prior to hatching. PMID- 8467895 TI - Trypanosoma cruzi: characterization of two recombinant antigens with potential application in the diagnosis of Chagas' disease. AB - A genomic library of Trypanosoma cruzi, constructed in the vector lambda gt11, was screened with a hyperimmune rabbit antiserum against tissue culture trypomastigotes. Two clones, B12 and B13, containing inserts of 350 and 600 bp, respectively, were isolated. Sequencing data indicated that both clones present a pattern of tandemly repeated nucleotide units of 60 bp for B12 and 36 bp for B13. Southern blot analysis suggests that both corresponding genes exist as a single copy. The inserts of both recombinants were subcloned in the vector pMSgt11, in phase with the lacZ gene. Recombinant proteins were affinity purified on pAPTG agarose columns and employed to immunize rabbits, as well as to immunoselect human chagasic antibodies. By Western blot, antibodies to B12 reacted with bands of 230 kDa in trypomastigotes and 200 kDa in epimastigotes, while those to B13 identified bands of 140 and 116 kDa in trypomastigotes and epimastigotes. Immunoprecipitation of radioiodinated parasites revealed that the 140-kDa antigen recognized by antibodies to B13 is located on the membrane of trypomastigotes but not epimastigotes. The potential application of either recombinant antigen in the serological diagnosis of Chagas' disease was evaluated initially by RIA. It was observed that B13 presents a very good performance with sensitivity of 97%. For B12, the corresponding value was 82%. The reactivity to B13 was also evaluated by ELISA tests run in parallel with conventional serological reactions for Chagas' disease. Analysis of 209 serum samples indicates that B13 presents similar or even better performance in relation to the use of total epimastigote antigens, making it a promising candidate for the diagnosis of Chagas' disease. PMID- 8467896 TI - Schistosoma mansoni: membranes from adult worms reversibly perturb shape, volume, and membrane organization of intact human red blood cells. AB - Adult forms of Schistosoma mansoni ingest host (human) red blood cells (RBCs). To elucidate potential mechanisms by which contact with adult parasites perturbs RBC membranes, we studied the effects of the membrane fraction of isolated schistosomes on RBC shape, volume, potassium ion content, and phospholipid and transmembrane protein lateral mobility. S. mansoni-treated RBCs exhibited rapid but spontaneously reversible shape change from discocytes to spheroechinocytes, reversible decrease in cell volume, and rapid loss of intracellular potassium ions. Treated RBCs also showed rapid but spontaneously reversible immobilization of membrane phospholipids and of band 3, the major transmembrane protein. These data suggest that components of adult S. mansoni membranes can perturb host RBC volume and membrane organization. In the absence of RBC lysis, RBC metabolic and repair mechanisms can reverse these effects. PMID- 8467897 TI - IgE antibody responses in bronchoalveolar spaces of rats infected with Nippostrongylus brasiliensis. AB - IgE levels in the bronchoalveolar lavage fluids (BALF) of rats increased significantly following infection with Nippostrongylus brasiliensis. This increase corresponded with a concurrent increase in serum IgE levels. However, a comparison of IgE to albumin ratio in both BALF and serum suggested local accumulation and/or production of IgE in the bronchoalveolar spaces rather than leakage from serum. Subsequent analysis of BALF showed presence of heat-labile PCA activity with highest anti-worm titer (1:64) on Days 11-16 postinfection (pi). Secondary infection resulted in up to a fourfold increase in PCA activity compared to primary infection. Immunoblot analysis showed that these parasite specific IgE antibodies in BALF recognized many proteins of adult worms ranging from 16-290 kDa. IgE antibodies in serum and BALF showed similarities in their reactivities toward adult worm antigens. However, the IgE antibody reactivities to different antigens varied significantly among different days pi. Depletion of IgG from BALF and serum resulted in more intense binding by IgE antibodies to antigens than when IgG was not depleted. Concurrent with the elevated levels of IgE antibodies, there was a significant increase in the levels of histamine in BALF, suggesting activation of mast cells. Thus, following N. brasiliensis infection there is an abundance of parasite-specific IgE antibodies in the lower respiratory tract and IgE-mediated pathways of inflammation appeared to be activated in the lungs. PMID- 8467898 TI - Plasmodium falciparum: stage-specific ribosomal RNA as a potential target for monitoring parasite development in Anopheles stephensi. AB - The transcriptional switch of Plasmodium falciparum ribosomal RNA A gene to the C gene was demonstrated during the developmental transition from the vertebrate blood stage to the invertebrate sporozoite stage. Expression of the sporozoite specific C gene in infected mosquitoes was not detected until Day 10 postinfectious blood meal, the time of mature oocyst formation on the midgut. As a potential target for monitoring malaria parasite development in mosquitoes, oligonucleotide probes based on sequences of small subunit ribosomal RNA were evaluated for specificity and sensitivity by filter blot hybridization against different species and stages of malaria parasites. Probes PfC02 and PfA02 were selected as the most sensitive for sporozoite and blood stage parasites, respectively. Filter blot hybridization using probe PfC02 resulted in sensitivity comparable with microscopic dissection in single mosquitoes, detecting mosquitoes with an average of 1.2 oocysts per gut or as few as 800 salivary gland sporozoites. PMID- 8467899 TI - Leishmania mexicana amazonensis: effect of heat shock on the spliced leader RNA and its ribonucleoprotein particle SL RNP. AB - Trypanosomatid parasites of the genus Leishmania experience a temperature shift from 22-38 degrees C to 33-37 degrees C while being transmitted from the invertebrate vector to the mammalian host. Expression of many protein-coding genes in protozoan parasites that cycle between two hosts have been shown to be thermosensitive, and temperature changes most probably serve as a major regulatory factor during stage differentiation. We present here our studies on effects of physiological temperature shift on the steady-state and nascent synthesis of the spliced leader SL RNA, as well as on its small RNP particle, SL RNP. Northern blot analysis showed no significant changes in the steady-state level of SL RNA at elevated temperatures. Neither were any alterations detected at the two different temperatures in nascent transcription of the SL RNA gene, examined in cells made permeable by treatment with lysolecithin. Fractionation of cell extracts on Cs2SO4 gradients indicated that temperature elevation led to changes in SL RNP particles. Alterations in these particles upon heat shock were also observed by separation on polyacrylamide gels, but only in the presence of urea, indicating that the differences caused by elevation of temperature were revealed exclusively under stringent fractionation conditions. PMID- 8467900 TI - Eimeria tenella: characterization of a 5S ribosomal RNA repeat unit and its use as a species-specific probe. AB - The oocysts of Eimeria tenella, one of the most pathogenic of several species causing chicken coccidiosis, are difficult to distinguish microscopically from several other infective Eimeria species. One copy of a gene coding for 5S ribosomal RNA has been cloned from E. tenella and sequenced. A coding region of 120 nucleotides and an intergenic region of 608 nucleotides together make up a 5S rRNA repeat unit, of which there are many copies tandemly repeated in the genome. The intergenic region is species-specific and sequences derived from it can be used for species identification by polymerase chain reaction (PCR). The PCR procedure described here is particularly sensitive, with fewer than 10 oocysts sufficing to give a positive result. This method may also be useful for the identification by PCR of other cyst-forming parasites. PMID- 8467901 TI - Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria. AB - The speed and stage specificity of antimalarial drug action on the metabolic activities of cultured Plasmodium falciparum were studied for chloroquine (CQ), quinine (QN), artemisinin (AR), and sodium artelinate (SA). CQ had the most rapid onset of action on [3H]hypoxanthine and [3H]isoleucine uptake, reaching 50% of its maximum effect in 1.8 hr compared with 3.5-7.4 hr for the other three drugs. In contrast there was a lag time of 1-4 hr before AR and SA had a measurable inhibitory effect, although after this delay antimalarial action was very rapid. Parasite glycolysis was relatively drug resistant; the inhibition of lactate production was < 60% of that for [3H]hypoxanthine and [3H]isoleucine uptake. The susceptibility of P. falciparum changed markedly as the parasite matured. Maximum drug effects occurred at the late ring and early trophozoite stage, which corresponds to the time at which the most rapid increases in synthetic and glycolytic activities occur. Mature schizonts and young rings were relatively unaffected by the antimalarial drugs. Young rings were particularly resistant to QN. Schizonts multiplied successfully in the presence of relatively high concentrations of all four drugs. The two artemisinin compounds had the broadest time window of action and may be particularly suitable for the treatment of severe malaria. PMID- 8467902 TI - Trypanosoma brucei: unusual expression-site-associated gene homologies in a metacyclic VSG gene expression site. PMID- 8467903 TI - Unique reaction of a barley peroxidase with hydrogen peroxide. AB - The reaction of barley peroxidase BP 1 with H2O2 is markedly different from that of other peroxidases. Saturation kinetics and a strong pH dependence over the accessible pH range from 3.09 to 5.08 are observed. At pH 3.8, native BP 1 has maxima at 401, 498 and 635 nm, cpd 1 at 403 nm, and cpd II at 407 and 521 nm with a shoulder at 553 nm. Both cpds I and II appear to be incompletely formed. Isosbestic points between native BP 1 and cpd I occur at 365 and 416 nm, while an isosbestic point in the Soret region between cpd I and cpd II has been observed at 410 nm. Between cpd II and a not yet identified intermediate isosbestic points have been observed at 408, 455 and 526 nm. PMID- 8467904 TI - Over-expression of protein kinase C-alpha enhances platelet-derived growth factor and phorbol ester- but not calcium ionophore-induced formation of prostaglandins in NIH 3T3 fibroblasts. AB - Over-expression of human protein kinase C-alpha in murine NIH 3T3 fibroblasts is associated with an increased platelet-derived growth factor- and phorbol ester mediated formation of prostaglandins, whereas the calcium ionophore-induced release of arachidonic acid metabolites is unaffected; however, the differences of arachidonic acid and prostaglandin formation are much more pronounced with platelet-derived growth factor than with phorbol ester. Platelet-derived growth factor induces an identical elevation of intracellular free calcium in control and protein kinase C-alpha over-expressing cells: the phorbol ester has no effect on intracellular free calcium in both cell lines. These results demonstrate that protein kinase C-alpha may couple to arachidonic acid cascade in NIH 3T3 fibroblasts. PMID- 8467905 TI - The two Staphylococcal bi-component toxins, leukocidin and gamma-hemolysin, share one component in common. AB - Staphylococcal bi-component toxins, leukocidin and gamma-hemolysin, consist of two protein components, i.e. F and S for leukocidin and H gamma I and H gamma II for gamma-hemolysin. In this study we purified H gamma I and H gamma II to homogeneity from the culture medium of Staphylococcus aureus RIMD 310925 and compared their properties with those of F and S purified from the same source. The N-terminal 59- and C-terminal 2-residue amino acid sequences, apparent molecular mass, and isoelectric point of purified H gamma I were the same as those of F. In an Ouchterlony double diffusion test a fused line without spur was formed between F and H gamma I using either anti-F or anti-H gamma I antibodies. A synergistic action of F and H gamma II caused hemolysis of human red blood cells, and H gamma I acted synergistically with S to exhibit leukocidin activity. We conclude that the two toxins share one protein component (F = H gamma I) in common and leukocidin- and gamma-hemolysin-specific activities are determined by S and H gamma II, respectively. It is also reported that the N-terminal 58 residue sequence of H gamma II is 72% similar to the corresponding sequence of S. PMID- 8467906 TI - Mercury inhibition at the donor side of photosystem II is reversed by chloride. AB - Mercury is an environmental contaminant that strongly inhibits photosynthetic electron transport, photosystem II being the most sensitive target. We investigated in greater detail the effect of mercury using photosystem II submembrane fractions of higher plants. Oxygen evolution was strongly inhibited and variable chlorophyll fluorescence was severely quenched by mercury. Chloride, an inorganic cofactor known to be essential for the optimal function of photosystem II, significantly reversed the inhibitory effect of mercury. However, calcium, another essential cofactor, showed no reversal capacity. It is concluded that on the donor side of PSII, mercury exerts its action by perturbing chloride binding and/or function. Considering the exceptional affinity of mercury for sulfhydryl groups of proteins, the results suggest the implication of cystein residue(s) in maintaining structural and functional integrity of photosystem II. PMID- 8467907 TI - The choline transporter is the major site of control of choline oxidation in isolated rat liver mitochondria. AB - The degree of control exerted by the mitochondrial choline transporter over the oxidation pathway was measured in isolated rat liver mitochondria. Choline transporter activity was titrated with hemicholinium-3, a known competitive inhibitor of the transporter. It was shown that the rate of betaine efflux from mitochondria was an accurate measure of choline oxidation. The relative rate of choline oxidation was measured as a function of the relative degree of inhibition of the transporter. The resulting data gave a flux control coefficient over choline oxidation of 0.9 for the choline transporter. It is concluded that the choline transporter is the major site for control of choline oxidation in isolated rat liver mitochondria. PMID- 8467908 TI - Phosphorylation of ribosomal proteins by the vaccinia virus B1R protein kinase. AB - Two proteins of the 40S ribosomal subunit were shown to be phosphorylated in vitro by a vaccinia virus-encoded serine/threonine protein kinase. These were identified by two-dimensional gel electrophoresis as ribosomal proteins Sa and S2 and were shown by phosphoamino acid analysis to both be phosphorylated on serine and threonine residues. The three phosphorylated forms of S2 produced by the B1R protein kinase in vitro matched the phosphorylated forms of S2 previously observed in cells infected with vaccinia virus. These data strongly suggest that this enzyme is responsible for the phosphorylation of S2 and Sa which occurs early during vaccinia virus infection. PMID- 8467909 TI - AT(D)PMg-induced dissociation of the alpha 3 beta 3 complex of the F1-ATPase from a thermophilic Bacillus PS3 into alpha 1 beta 1 heterodimers is prevented by mutation beta (Y341C). AB - AT(D)PMg induces dissociation of the alpha 3 beta 3 complex of F1-ATPase from a thermophilic Bacillus strain. PS3, into the alpha 1 beta 1 heterodimers [(1991) Biochim. Biophys. Acta 1056, 279-284] but the location of the AT(D)PMg binding site responsible is not known. From the analysis of AT(D)PMg binding properties of the isolated mutant beta subunit, beta(Y341C), and the stability of the alpha 3 beta(Y341C)3 complex in the presence of AT(D)PMg, we conclude that binding of AT(D)PMg to the Tyr-341 site of the beta subunit(s) in the alpha 3 beta 3 complex triggers the dissociation of the alpha 3 beta 3 complex into the alpha 1 beta 1 heterodimers. PMID- 8467910 TI - A1F-B, a novel CCAAT-binding transcription activator that interacts with the aldolase B promoter. AB - We describe here a 70 kDa transcription factor A1F-B, which preferentially binds to an element encompassing a CCAAT motif on the rat aldolase B promoter. Comparison of binding specificities, relative molecular masses, and subunit compositions with those of other known CCAAT-binding factors indicated that A1F-B is a novel member of CCAAT-binding factors. PMID- 8467911 TI - A thioredoxin-independent fully active NADP-malate dehydrogenase obtained by site directed mutagenesis. AB - A triple cysteine mutant of sorghum leaf NADP-malate dehydrogenase has been constructed by site-directed mutagenesis, combining the previously obtained mutation of the two N-terminal cysteines with the mutation of the most internal of the two C-terminal cysteines. The construct, over-expressed in E. coli, yielded an always active, dithiol-insensitive enzyme. It can be concluded that the dithiol activation of the unmodified enzyme involves a maximum of two different disulfides per subunit, and that none of the mutated cysteines is implicated in catalysis. PMID- 8467912 TI - Molecular cloning of a cDNA encoding calmodulin from Neurospora crassa. AB - A full-length cDNA encoding Neurospora crassa calmodulin was isolated from a lambda ZAP II cDNA expression library. The open reading frame encodes a protein of 148 amino acid residues with a calculated M(r) of 16,865 Da. Using site directed mutagenesis, the complete cDNA was ligated into a trc promoter-regulated bacterial expression vector to allow expression of N. crassa calmodulin in E. coli. The expressed protein was found to be identical to the native protein on the basis of some of its biochemical properties. Finally, Southern analysis of restriction digests of genomic DNA indicates that calmodulin is encoded by a single-copy gene. PMID- 8467913 TI - Identification of an actin binding region in aldolase. AB - Fragmentation of the actin binding glycolytic enzyme, aldolase, with cyanogen bromide yields an 18K actin binding fragment which corresponds to residues 1-164 of the aldolase sequence. Within this fragment there is a region of sequence (residues 32-52) which is highly homologous to a region of sequence near the C terminus of actin itself and which is also found in the actin binding domains of a number of other actin binding proteins. A synthetic peptide corresponding to the aldolase sequence 32-52 encompassing this region of homology binds to F-actin and specifically competes with native aldolase for binding to this cytoskeletal protein. PMID- 8467914 TI - Termination of right handed helices in proteins by residues in left handed helical conformations. AB - An analysis of 636 helical segments, ranging in length from 4 to 32 residues, from 123 independent protein crystal structures reveals that helix termination by residues in left handed (alpha 1) helical conformations is a common occurrence. Gly and Asn residues are the most frequent alpha L helix terminators, with the former having a very high propensity to adopt such conformations. The alpha R alpha R-alpha R-alpha L segment at the C termini of protein helices often possesses a 6--> 1 (pi-type) hydrogen bond between the CO of residue i and the NH of residue i + 5 with residue i + 4 occurring in the alpha L conformation. A stereochemical analysis of 216 examples shows that in 62 cases the 6-->1 hydrogen bond is absent. The present analysis provides a quantitative measure of the propensity of the 20 amino acids to adopt alpha L helix terminating conformations. PMID- 8467915 TI - Stereo-specific inhibition of sea urchin envelysin (hatching enzyme) by a synthetic autoinhibitor peptide with a cysteine-switch consensus sequence. AB - Inhibition of envelysin, a metalloproteinase which dissolves the fertilization envelope of sea urchin embryo, was studied using a synthetic autoinhibitor peptide. Ac-Pro-Arg-Cys-Gly-Val-Pro-Asp-Val-NH2, with a 'cysteine-switch' consensus sequence. Although its effect is reversible, the hatching of sea urchin embryos was effectively delayed by 0.5 mM of the peptide. When alpha 1-proteinase inhibitor was used as the substrate, envelysin was inhibited by the autoinhibitor and an Ala6 analogue, but not by a D-Cys3 analogue. However, envelysin was weakly inhibited by both D- and L-cysteines to the same extent. Snake venom alpha protease exhibited cleavage and inhibition behavior similar to envelysin with a little weaker stereo-specificity. The results suggest that the coordination of the autoinhibitor Cys residue with the envelysin active site Zn is established only after the amino acid residues on both sides of the Cys residue get into an appropriate interaction with the catalytic site residues, and that the precise orientation of the cysteine SH group is essential. By contrast, thermolysin was weakly inhibited by the three peptide non-stereo-specifically. Furthermore, thermolysin cleaved the autoinhibitor at the Cys3 Gly4 bond when incubated without substrate. PMID- 8467917 TI - Shared governance: participatory management. PMID- 8467916 TI - Cloning, expression and characterization of human kininogen domain 3. AB - The internal domain 3 of the heavy chain of human kininogen, a cysteine proteinase inhibitor, was amplified by a polymerase chain reaction from the kininogen cDNA clone phKG36. The DNA fragment was expressed in Escherichia coli using the ompA expression vector pASK40 and the resulting protein was isolated from periplasm, purified by S-carboxymethylpapain affinity- and ion-exchange chromatography. The recombinant human kininogen domain 3 is 92% pure, reacts with anti-kininogen antibodies and is actively inhibitory. The expected amino acid sequence of ANSM-[G253-S377] kininogen was confirmed; the inhibitor has a molecular mass of 14,396 Da and an isoelectric point of 6.0 (pH). The determined Ki values of the complexes with papain and cathepsin L are similar to those measured previously with proteolytically liberated kininogen domain 3, and those of single-domain cystatins, like chicken egg white cystatin. However, recombinant kininogen domain 3 is a weak inhibitor of cathepsin B (Ki = 63 nM) as it has been found for native L-kininogen (Ki = 340 nM). PMID- 8467918 TI - Is it time for self-assessment? PMID- 8467919 TI - Small group training in breast screening using volunteer leaders. PMID- 8467920 TI - Health status of women in Florida. PMID- 8467921 TI - The contraceptive decision: update on methods/considerations. PMID- 8467922 TI - Report of Institute of Member Collective Bargaining. PMID- 8467923 TI - Job sharing among camp nurses. PMID- 8467924 TI - The paradigm shift from traditional obstetrics to single room maternity care. PMID- 8467925 TI - Ethical concerns affecting Florida nurses: survey results from FNA Convention. PMID- 8467926 TI - [Thyroid and growth factors]. AB - Although TSH is the major regulator of thyroid growth and function, the role of TSH in thyroid cell growth in vitro is controversial. Recent studies have shown that a number of growth factors, cytokines, vitamins, hormones and other reagents including iodide, lithium or retinoids modulate proliferation of cultured thyroid cells. Insulin-like growth factors (IGFs) stimulate growth of thyroid cells from a variety of species and also enhance expression of differentiated functions stimulated by TSH. Epidermal growth factor (EGF), fibroblast growth factor (FGF), and Transforming growth factor (TGF)-alpha are also mitogens to thyroid cells, but they are inhibitory to differentiated functions. In contrast, TGF-beta is a potent inhibitor to thyroid cell growth and functions. Indirect evidence suggests that these growth factors are involved in growth regulation of normal and neoplastic thyroid cell growth in autocrine/paracrine manner. PMID- 8467927 TI - [Structure and function of the thyroid hormone receptor]. AB - Cloning of the thyroid hormone receptor and its identification as a cellular counterpart of the viral oncogene v-erbA was a major breakthrough in the study of thyroid hormone action. However, contrary to our initial expectations, many astonishing findings which have accumulated since the receptor cloning, especially the presence of two receptor types, made the elucidation of the thyroid hormone action extremely complicated. In this paper, we mainly did a phylogenic comparison of the amino acid sequence between alpha- and beta-type receptor from Xenopus laevis to humans, hoping to obtain some clue to clarify the functional differences between these receptors. There are several consistent amino acid differences between alpha- and beta-receptor through species in the DNA binding domain, one of which is non-conservative and is located in the portion supposed to be critical to the protein-protein interaction. We believe that clarification of the physiological significance of the presence of two receptor types will facilitate the study of thyroid hormone action. PMID- 8467928 TI - [A rare case of primary aldosteronism due to bilateral functioning adrenocortical adenomas]. AB - A 43-year-old man was admitted to our hospital in January, 1991 for further examination of polydipsia, polyuria and hypertension. He had had a personal history of hypertension since 1976 and of diabetes mellitus since 1982. Physical examination and routine laboratory studies showed that the patient was characterized by asymptomatic hypertension in the presence of hypokalemia and increased urinary potassium excretion. Plasma aldosterone concentrations (PAC) were elevated and plasma renin activity (PRA) was suppressed, resulting in a considerable increase in the ratio of PAC to PRA. PAC was not normally suppressed by saline infusion (2 1/2h, iv). PRA remained suppressed and PAC did not rise after stimulation with iv injection of furosemide (40 mg) in combination with walking for 60 min. PAC was increased in response to ACTH injection (0.25 mg, iv) but not suppressed by dexamethasone administration (2 and 8 mg/day, po). PAC did not rise after iv infusion of angiotensin II (20 ng/kg/min for 30 min). Venous sampling showed that PAC was considerably elevated in the bilateral adrenal vein. CT and MRI demonstrated tumor mass in the bilateral adrenal gland and the remaining normal portion in the left adrenal gland. Scintigraphic imaging with 133I-aldosterol during dexamethasone suppression provided bilateral uptake in the adrenals. Oral administration of spironolactone (375 mg/day) suppressed blood pressure and elevated PRA and serum potassium. Elevated PCA and PRA levels as well as hypertension were corrected by right-total and left-subtotal adrenalectomy performed in March, 1991. However, impaired glucose tolerance was not changed after surgery, and plasma glucose levels were well controlled with a small dose of insulin (9U/day). Pathological studies revealed adrenocortical adenoma cells of clear cell type with spironolactone bodies in the bilateral adrenal tumors. These findings indicate that this is a very rare case of primary aldosteronism due to bilateral functioning adrenocortical adenomas, which is accompanied by diabetes mellitus. PMID- 8467929 TI - [Free fatty acid responses to growth hormone (GH)-releasing factor and the GH-GH receptor axis]. AB - The functional assessment of GH receptor has been previously performed by GH induced somatomedin (SM) generation test. There is a specific GH receptor on adipocytes, and GH induces lipolysis with an increment of plasma free fatty acid (FFA). In this report, we examined GH and FFA responses to GRF loading tests and GH-binding protein, which reflects the tissue GH-receptor concentration, in 30 short children, and we evaluated the lipolysis mediated by GH and GH-receptor axis. Following GRF administration, there was a definite increase in plasma FFA levels, which mainly consisted of palmitic acid and oleic acid on HPLC analysis. In the group of GH high responders, peak GH levels more than 30 ng/ml, the increments of FFA were apparently more than those in the GH low responders, peak GH levels less than 30 ng/ml. There was a significant correlation between the integrated GH secretion and the integrated FFA net-increments. In the GH low responders, the integrated FFA net-increments significantly correlated with their serum GH-binding protein activities. The net increments of FFA were also correlated with basal SM-C levels. In a case of GH-resistant dwarfism, in which GH-binding protein activity was markedly reduced, the patient's GH secretion to GRF as high as 51 ng/ml did not induce any increment of FFA levels. These results suggest that FFA responses to GRF loading depend on the integrated GH secretion and tissue GH-receptor content. FFA measurements in GRF test samples may be a simple and useful method for the functional assessment of GH and GH-receptor axis. PMID- 8467930 TI - [The effect of alacepril on insulin sensitivity in patients with essential hypertension]. AB - The aim of this study was to determine the effect of angiotensin-converting enzyme inhibitor, alacepril, on insulin sensitivity in patients with essential hypertension (EHT). Ten patients (5 men and 5 women) with EHT (3 with mild diabetes and 2 with borderline glucose tolerance) participated. We measured insulin sensitivity using the two-hour euglycemic-hyperinsulinemic clamp technique and plasma glucose and insulin responses to a 75 g oral glucose tolerance test (75 g OGTT) before and after 6-8 weeks of treatment with alacepril (dose, 50 mg/day). Glucose infusion rate (GIR) during the last 30 min of the clamp study increased from 5.83 +/- 0.70 to 6.59 +/- 0.65 mg per kilogram of body weight per minute (P < 0.05) after treatment with alacepril. The insulin sensitivity index, which was calculated by dividing the GIR by the mean insulin concentration during the same period of the clamp, also increased from 5.91 +/- 0.66 to 7.20 +/- 0.90 (P < 0.05) after treatment with alacepril. Plasma glucose responses to a 75 g OGTT were changed from diabetic pattern to borderline pattern in two patients and from borderline pattern to normal pattern in one patient after treatment with alacepril. Body weight did not significantly change throughout the study in any of the patients studied. Our study demonstrated that alacepril significantly improves insulin sensitivity in patients with EHT. PMID- 8467931 TI - A new theory of relativity? PMID- 8467932 TI - Outpatient colchicine poisoning. AB - The clinical effectiveness of colchicine for acute gouty attacks is well documented. Its toxicity and low therapeutic index have also been previously described. The following case report, although nonfatal, illustrates the toxicity of colchicine and the dangers of inadequate doctor-patient communication involving highly toxic medications. PMID- 8467933 TI - Advising and stimulating health education in schools, 1965-1993. PMID- 8467934 TI - Tricky business: discharging a physician-employee. PMID- 8467935 TI - Screening for lung cancer: it's still not worthwhile. PMID- 8467936 TI - A physical therapist responds. PMID- 8467937 TI - Job dissatisfaction: dentistry's taboo topic. PMID- 8467938 TI - Prepare a cash budget to meet your goals. PMID- 8467939 TI - Marketing your practice. PMID- 8467940 TI - Interest-rate shock. PMID- 8467941 TI - Properly handling reference requests. PMID- 8467942 TI - Every 'nook and cranny' is put to use. PMID- 8467943 TI - Thinking about the unthinkable. PMID- 8467944 TI - Intraoral video enhances presentations. PMID- 8467945 TI - Conservative crown build-out using hybrid composite materials. PMID- 8467946 TI - Enamel microabrasion technique. PMID- 8467947 TI - Success secrets of mandibular anesthesia. PMID- 8467948 TI - Composite choices expand. PMID- 8467949 TI - Nucleoside transport in parasites--current status and methodological aspects. PMID- 8467950 TI - Purification and partial characterization of 200 kDa oncofetal antigen from radiation induced murine lymphocytic lymphoma. AB - 1. A 200 kDa glycoprotein (gp200) oncofetal antigen was purified from solubilized membranes of a radiation-induced murine lymphocytic lymphoma cell line (XR11-5T), grown in syngeneic RFM mice, by successive gel chromatography of the active fraction on lentil lectin agarose, Q- and S-Sepharose and Superose-12 using an FPLC system. 2. A murine monoclonal antibody 115, produced by the syngeneic immunization of adult male C57BL/6N mice with 12-day mouse fetal cells, was used in a slot blot antibody assay to follow up the active fractions. 3. The purified glycoprotein has a pI of 5.4. 4. Treatment of radiolabeled gp200 with neuraminidase caused a slight reduction in size due to the removal of sialic acid groups and a shift in pI to 6.3. 5. Treatment of gp200 with different glycosidases shows that gp200 is susceptible to N- and O-glycanase but not to endoglycosaminidase H. 6. On extraction of gp200 with Triton X-114 it partitions exclusively into the detergent-rich fraction consistent with being an integral membrane protein. PMID- 8467951 TI - Interaction of N-methyl-anthraniloyl-labelled porcine apolipoprotein A-I with porcine lecithin: cholesterol acyltransferase: an energy transfer study. AB - 1. To investigate whether a direct protein-protein interaction between apoA-I and lecithin:cholesterol acyltransferase (LCAT) is necessary for the activation of the enzyme, apoA-I was labelled with N-methylisatoic anhydride at lysine residues. The intermolecular resonance energy transfer from tryptophan residues of LCAT (donor) to N-methyl-anthraniloyl (NMA)-labelled apoA-I (NMA-apoA-I) (acceptor) was used as a sensitive fluorescence method for studying molecular interactions. 2. In the absence of lipids no fluorescence energy transfer was measurable. 3. Fluorescence energy transfer occurred from LCAT to NMA-apoA-I in the presence of liposomes with phospholipid/cholesterol ratios ranging from 5:1 to 18:1 and regardless whether only 1 or up to 5 NMA-apoA-I molecules resided at the liposome surface. 4. This indicates a preferred binding of the enzyme directly to or in spatial proximity to the activator protein NMA-apoA-I even if enough space at the liposome surface is available to allow LCAT binding at a distance, where no energy transfer is measurable. PMID- 8467952 TI - Regulation of horse-liver glutathione reductase. AB - 1. The enzyme was rapidly inactivated by NAD(P)H, GSH, dithionite or borohydride, while activity increased in the presence of NAD(P)+ or GSSG. NADH was more efficient for inactivation than NADPH. Redox inactivation required neutral or alkaline pH, was maximal at pH 8.5, and depended on the presence of metal cations. 2. GSSG and dithiothreitol fully protected the enzyme from inactivation at concentrations stoichiometric with NAD(P)H. Ten-fold higher ferricyanide or GSH concentrations were required to obtain partial protection. NAD+ or NADP+ were quite ineffective. 3. GSSG fully reactivated the inactive enzyme at 38 degrees C and neutral to acidic pH (5.5-7.5). Reactivation by dithiothreitol was accomplished in short periods of time at pH 8.5 although the activity was progressively lost afterwards. Ferricyanide and GSH also reactivated the enzyme to different extents. PMID- 8467953 TI - Induction of prothrombin biosynthesis and inhibition of gamma carboxylase activity in experimental models of liver regeneration and fibrosis. AB - 1. When acute liver damage is induced in rats treated with CCl4, both prothrombin biosynthesis and gamma carboxylase activity decreases, originating a prolongation of prothrombin time in plasma. 2. Then, during the regenerative process, prothrombin biosynthesis increases higher than normal, but gamma carboxylase activity remain decreased. In this case, prolongation of prothrombin time occurs in spite of high levels of descarboxylated prothrombin in plasma. 3. An increase of descarboxylated prothrombin in plasma is also detected in the CCl4-liver fibrosis model. PMID- 8467954 TI - Association of cytosolic lipids with fatty acid synthase from lactating mammary gland. AB - 1. Membrane-free cytosol contained over 4% of both the total lipids and phospholipids present in homogenates of lactating rat mammary gland, and much of this lipid was associated with a high molecular weight complex isolated from cytosol by gel exclusion chromatography or by density gradient centrifugation. 2. This complex principally consisted of polypeptides with apparent molecular weights of 220 and 116 kDa. Lipids associated with this complex were transferred to endoplasmic reticulum and to intracellular lipid droplet precursors of milk lipid globules upon incubation in a cell-free system. 3. This lipoprotein complex was abundant in cytosol from lactating mammary gland, but was diminished in amount in cytosol from involuted mammary glands. The 220 kDa constituent of this complex was identified as the monomer of fatty acid synthase. 4. These results suggest that fatty acid synthase complex in lactating mammary gland may function in transfer of lipids necessary for formation or growth of lipid droplet precursors of milk lipid globules. PMID- 8467956 TI - Distribution of serine esterase activity in the lymphoid system of C57BL/6 mice, effect of aging on the enzymatic activity. AB - 1. The activity of serine esterase (SE) was investigated in the lymphoid system of C57BL/6 mice. SE activity increased in the lymphoid tissues with their content of mature T-lymphocytes, except that high levels were also observed in various populations of bone marrow cells. 2. The maturation of T-lymphocytes in the thymus was accompanied by an increase in their SE activity. 3. Experiments on the influence of age on SE activity showed that while thymocytes were not affected, a three-fold increase in activity occurs in spleen lymphocytes between the ages of 26 and 78 wk. PMID- 8467955 TI - Degradation of bone matrix proteins by osteoclast cathepsins. AB - 1. The degradation of the bone matrix proteins osteocalcin, osteonectin and alpha 2HS-glycoprotein by human cathepsins B and L and human osteoclastoma cathepsins has been investigated. 2. Intermediate degradation products (M(r) > 12 kDa) were not observed during the digestion of alpha 2HS-glycoprotein and osteonectin by cathepsins B and L although they were observed with some of the osteoclastoma cathepsins. Most of the osteoclastoma cathepsins were capable of degrading these two proteins to small peptides at comparable rates. 3. Each cathepsin produced a different pattern of osteocalcin degradation products. 4. The extensive range of non-collagenous proteins in bone matrix may necessitate the production by osteoclasts of cathepsins with different specificities during bone resorption. PMID- 8467957 TI - PLA2 activity in rat liver nuclei. AB - 1. Subcellular fractions of rat liver were assayed for PLA2 activity. 2. The PLA2 assay measures the release of [3H]oleic acid from phospholipids, using labeled E. coli as substrate. 3. Nuclear fractions contained PLA2 activity, which was Ca2+ dependent and could not be explained from mitochondria, microsomal or plasma membrane contamination. 4. The Vmax value of nuclear PLA2 is 0.30 +/- 0.04 pmol oleic acid/min/mg protein; its Km value is 0.86 +/- 0.12 microM, similar to that of mitochondrial PLA2. 5. We conclude that rat liver nuclei contain PLA2 activity. PMID- 8467958 TI - Strong sequence patterns in eukaryotic promoter regions: potential implications for DNA structure. AB - 1. Analysis of eukaryotic sequences reveals recurring trends in upstream regions. Oligomers composed of (G/C)n and (A/T)m blocks are preferentially flanked by (G/C)2 doublets on their 3' rather than on their 5' ends, that is (G/C)n(A/T)m(G/C)2 > (G/C)n+2(A/T)m. 2. These trends are stronger for larger n and smaller m. Additional trends are outlined below. 3. The trends are correlated with DNA structural parameters, in particular with twist and roll angles. 4. Generally, the trends hold if the base pair step joining the 5' (G/C)2 doublet to the (G/C)n (A/T)m oligomer is not undertwisted and is not strongly rolled into the major groove. 5. Other DNA parameters crucial for DNA-protein interactions are discussed as well. PMID- 8467959 TI - Purification and properties of a beta-1,4-xylanase from a cellulolytic extreme thermophile expressed in Escherichia coli. AB - 1. An endoxylanase (EC 3.2.1.8) was purified from an Escherichia coli strain carrying a xylanase gene from the extreme thermophile "Caldocellum saccharolyticum" strain Tp8T6.3.3.1. It was found to have an M(r) of 42,000 and an isoelectric point of approx. 5.0. 2. The enzyme showed optimum activity at pH 5.0-7.7 and had an activation energy of 44 kJ mol-1. It was stable at room temperature at pH 4.5-11.5 in the presence of 0.5 mg ml-1 bovine serum albumin. The half-life of the enzyme at 75 degrees C was 20 min at pH 6.0 in the presence of 0.5 mg ml-1 bovine serum albumin. 3. The xylanase had highest activity on oat spelts xylan, releasing xylobiose and some xylotriose. The Km for oat spelts xylan was 0.021% (w/v) at pH 6.0. 4. The enzyme had high activity on sugar cane bagasse hemicelluloses A and B, lower activity on larchwood xylan and also hydrolysed carboxymethylcellulose, 4-methylumbelliferyl beta-D-cellobioside and p nitrophenyl beta-D-cellobioside, but could not hydrolyse xylobiose. 5. It showed transferase activity on p-nitrophenyl beta-D-xylopyranoside. Xylose did not inhibit the enzyme. PMID- 8467960 TI - Effects of hyperthyroidism on glucose, glutamine and ketone-body metabolism in the gut of the rat. AB - 1. The metabolism of glucose, glutamine and ketone-bodies was studied in the small intestine of rats after 5 days of hyperthyroidism. 2. Portal-drained visceral bloodflow increased by 20.1% (P < 0.05) in hyperthyroid rats and was accompanied by a decrease in the arteriovenous concentration difference of glutamine (25.7%, P < 0.05), glutamate (22.0%, P < 0.05), alanine (20.9%, P < 0.05) and ammonia (20.6%, P < 0.05) and an increase in that of glucose (27.2%, P < 0.05), lactate (28.9%, P < 0.05) and ketone-bodies (163.2%, P < 0.001). 3. The gut of hyperthyroid rats showed increased rates of extraction of glucose, lactate and ketone-bodies. 4. Enterocytes isolated from hyperthyroid rats showed increased rates of utilization of glucose and ketone-bodies but that of glutamine were decreased. 5. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, citrate synthase and oxoglutarate dehydrogenase were increased (by 13.7-36.2%) in intestinal mucosal scrapings of hyperthyroid rats, whereas the activity of glutaminase was decreased (22.1-31.4%). 6. It is concluded that hyperthyroidism increases the rates of utilization of glucose and ketone-bodies but decreases that of glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine. PMID- 8467961 TI - Postpartum factors related to mother's attraction to newborn infant odors. AB - Hedonic responses to a variety of infant (general body, urine, and feces) and noninfant (lotion, cheese, and spice) odorants were compared in four groups of subjects: new mothers, mothers a 1-month postpartum, and female and male nonparents. Using standard scaling procedures, subjects rated each of the odorants twice on a scale from extremely unpleasant (-20.5) to extremely pleasant (+20.5). In addition, all subjects completed a set of attitude questionnaires, and mothers also answered a childbirth questionnaire and were observed while feeding their infants. PMID- 8467962 TI - Ultrasonic vocalization responses of rat pups to acute separation and contact comfort do not depend on maternal thermal cues. AB - In order to assess the importance of maternal thermal cues in controlling the acute USV responses of rat pups to contact with her body (the contact comfort response) and to separation from her, we drastically altered maternal temperature by inducing severe hypothermia so that maternal rectal and flank temperatures averaged more than 20 degrees C below normal and 10 degrees C below ambient levels during testing. Isolated 12- to 13-day-old pups showed reductions in USV when these cold dams were presented and brisk USV accelerations when the cold dams were removed from the test chamber. These responses closely resembled those of other pups tested with warm (36 degrees C) anesthetized dams. No significant differences were found in pups' USV contact comfort responses to cold and warm dams. For acute separation, prior maternal thermal properties and other factors were found to modulate the relative intensity of the marked USV increase elicited by this event. PMID- 8467964 TI - American Society for Biochemistry and Molecular Biology and Division of Biological Chemistry--American Chemical Society. Joint Meeting. San Diego, California, May 30-June 3, 1993. Abstracts. PMID- 8467963 TI - Salt appetite consequent on sodium depletion in the suckling rat pup. AB - The ontogeny of the behavioral ability to compensate for sodium deficit was studied in the rat. The experiments showed that: 1) Before weaning age, sodium depleted pups will increase their avidity for 3% NaCl solution; 2) the ability to select and drink a salt solution in response to a sodium deficit continues to evolve between 17-24 days of age, and that pups at these ages will modify their intake of salt and water as do adult rats when rectifying plasma osmolality; 3) The increased appetite for sodium is evident even when depleted preweanlings are dehydrated and provided with solid NaCl tablets to lick, showing that sodium appetite and hydrational status are already dissociated at this age; and finally, 4) sodium depletion first induces an increase in intake of orally infused 3% NaCl solution in 12-day-old pups. The picture of the development of salt appetite in the suckling rat that these findings present is of a precocious competence to meet a challenge to sodium homeostasis. In this respect salt appetite emerges in parallel to the other ingestive behaviors. PMID- 8467965 TI - [A multivariate prospective study of prognostic factors in 200 operated epidermoid cancers of the esophagus. Definition of patients for whom surgical resection was of benefit]. AB - From 1982 to 1991, 200 patients with squamous-cell esophageal cancers underwent operation. Sixteen prognostic parameters were prospectively collected and analyzed. The main aim of this study was to define the best preoperative criteria for selection for curative surgery and which patients would benefit most from radical resection. Squamous-cell head and neck carcinoma was associated in 43.5% of cases. Of these, 24% preceded the esophageal carcinoma while 19.5% were synchronous. Resection was curative (i.e. grossly complete) in 144 cases, palliative (leaving gross tumor behind) in 25 cases, and judged impossible in 31 cases. Twenty-one patients died during their hospitalization. Five-year survival, according to the Kaplan-Meier method, was 18 +/- 3.6% for all patients, and 27 +/ 4.8% for patients undergoing curative resection (including postoperative mortality). Palliative resections or invasion of adjacent organs, but not resection with positive lymph nodes, was thought to be synonymous with incurability. Multivariate analysis showed that the two principal statistically significant characteristics were the stage as determined by roentgenological and endoscopic evaluation (P = 0.003) (clearly assessable during initial work-up) and type of resection (complete or not) (P = 0.04). Tumor diameter, as determined on CT-scan (< or > than 30 mm), was at the limit of statistical significance (P = 0.09). A second multivariate analysis of prognostic factors was conducted in 128 patients undergoing resection with curative intent and who survived the initial postoperative period. Roentgenologic/endoscopic staging alone emerged as being statistically significant (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467966 TI - [Cancer of the esophagus: survival increases and indications become clear]. PMID- 8467967 TI - [Electronic sectorial ultrasound endoscopy in benign and malignant tumoral pathology of the stomach. Results in 30 patients]. AB - From October 1991 to July 1992, endoscopic ultrasound examination (EUS) was performed preoperatively in 30 patients with gastrointestinal disease with a new forward-view fiber optic gastroscope with a 5 and 7.5 MHz curved-array linear transducer mounted directly behind the lens. Before EUS examination, endoscopy with biopsy had established the diagnosis of gastric disease in 22 cases: 16 adenocarcinoma, 4 lymphoma, 1 carcinoid tumor and 1 gastric metastasis of a chorionic tumor. In the 8 other cases, endoscopic diagnosis with non productive biopsy was gastric ulcer (1 case), submucosal tumor (5 cases), and large fold gastritis (2 cases). EUS established a correct diagnosis in 6 of these 8 cases (2 leiomyoma, 1 lipoma, 1 lymphoma, 2 gastric linitis). Correct preoperative TN staging was accomplished by EUS in 83.3% and correct preoperative staging for N was accomplished by EUS in 90%. This study shows that EUS a curved-array transducer is useful in preoperative TN staging of gastric tumors. PMID- 8467968 TI - [Etiologies of a moderate and prolonged elevation of serum activity of transaminases: the end of "transaminitis"?]. PMID- 8467969 TI - [Contribution of liver biopsy and serology of hepatitis C virus to the diagnosis of a moderate and prolonged elevation of aminotransferases]. AB - The aim of this study was to evaluate the diagnostic usefulness of percutaneous liver biopsy and screening for hepatitis C virus antibodies with 1st and 2nd generation ELISA in asymptomatic blood donors with persistent (> 1 year) and moderate elevation (> 1.5 times the upper limit of normal) of serum alanine aminotransferase. The diagnosis was established from clinical, biological and ultrasound data before biopsies were obtained, then compared to the histological diagnosis. Thirty one of 56 blood donors who satisfied the preceding criteria accepted liver biopsy and were subsequently included in the study. An accurate diagnosis was proposed before biopsy in 20 cases. This was in agreement with the histological results in 19 cases but in 2 of these, unexpected lobular hepatitis was associated with the expected steatosis. Positive hepatitis C virus tests corresponded to chronic hepatitis in all cases (n = 5). No accurate diagnosis could be proposed in the 11 remaining cases owing to the lack of evidence of any etiology (n = 4) or because several potential etiologies were possible for the same subject (n = 7). Histological diagnoses were: isolated steatosis (n = 12), steatosis associated with lobular hepatitis (n = 7) or with chronic persistent hepatitis (n = 1), chronic active (n = 2) or chronic persistent hepatitis (n = 3), alcoholic hepatitis (n = 2), hemochromatosis (n = 1), and normal liver (n = 3). Liver biopsy is essential to the accurate etiological diagnosis of persistent and moderate elevation of aminotransferases despite hepatitis virus C tests which are associated with the correct diagnosis of chronic hepatitis in 16% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467970 TI - Exertional gastroesophageal pH-metry: a new provocative physiological test in the diagnosis of chest pain. AB - With the aim of determining the value of physical exercise as a provocative test for chest pain associated with gastroesophageal reflux, 67 patients presenting non-cardiac chest pain (normal coronary angiograms and no functional coronary artery alterations) with different characteristics (group A: at rest; group B: exertional or mixed-type) underwent exercise tests during 24-hour gastroesophageal pH-metry associated with electrocardiographic (EKG) monitoring. Thirty-four patients in group A (73.4%), and 12 in group B (57%) showed pathological reflux on 24-hour gastroesophageal pH-metry. Twelve patients in group A (25%) and 6 in group B (28.5%) (total ratio: 26.8%) presented positive responses to exercise, with concomitant occurrence of gastroesophageal reflux, typical pain, without EKG ischemic signals. Exertional pH-metry allowed to reach diagnostic certitude in 10 (14.9%) of 67 patients, 9 presenting 24-hour pH-metry results that only suggested "possible" diagnosis, and 1 without either pathological reflux or pain during prolonged monitoring: all these patients belonged to group A. The repetition of the test showed total reproducibility of the results, with "fixed thresholds" of exercise in 11 of 18 subjects (61.1%). These data suggest the usefulness of grouping different diagnostics (24-hour EKG, pH-metry and exertional test) to increase diagnostic certitude, mainly in patients with primary angina. Exertional pH-metry shows to be an efficacious provocative test, and the only based on a physiological stimulus. PMID- 8467971 TI - [A case of chylous ascites associated with exudative enteropathy complicating chronic pancreatitis of alcoholic origin]. AB - Chylous ascites is mainly due to malignant abdominal disease or cirrhosis. We report the case of chylous ascites associated with protein losing enteropathy caused by fibrotic compression of abdominal lymphatic vessels and superior mesenteric vein complicating alcohol-related chronic pancreatitis. This is the second case published in the literature. PMID- 8467972 TI - [Angiomyolipomas of the liver. Diagnostic and therapeutic aspects in 4 cases and review of the literature]. AB - In four cases, angiomyolipoma of the liver was discovered incidentally by ultrasound investigation. Based on a review of 26 other previously reported cases and as was borne out in our series, the diagnosis is suggested by the demonstration of fatty material on CT-scan and confirmed by needle aspiration biopsy. Magnetic resonance may be contributive as well. PMID- 8467973 TI - [Multiple microcystic cystadenomas of the pancreas without organic association. Apropos of a case]. PMID- 8467974 TI - [Toxic megacolon caused by loperamide-myorelaxants combination]. PMID- 8467975 TI - [Tracheal stenosis and hemorrhagic rectocolitis]. PMID- 8467976 TI - [Diarrhea induced by Cyclo 3 fort and lymphocytic colitis]. PMID- 8467977 TI - [Ulcerative colitis: secondary to the ingestion of lysine acetylsalicylate?]. PMID- 8467978 TI - [Combined radiological and endoscopic treatment of intrahepatic lithiasis. Value of intra-corporeal lithotripsy by pulsed laser]. PMID- 8467979 TI - [Projectile in the common bile duct: a rare cause of cholestatic jaundice]. PMID- 8467980 TI - [Treatment of and survival after epidermoid cancer of the esophagus in the department of Finistere between 1984 and 1988 (716 cases)]. AB - The incidence of esophageal cancer in the French county of Finistere is among the highest in France (26.7/10(5) for males). The authors analyzed the survival rates for squamous cell carcinomas from data of the Finistere tumor registry in order to describe different prognostic groups of patients using the multivariate Cox model. From 1984 to 1988, 716 patients with esophageal squamous cell carcinomas were registered in an overall population of 828,000 residents: 675 males and 41 females. Survival was calculated using the actuarial method. Six hundred and seventy five patients died before the point date (31 Dec 1989). Only one patient was lost to follow-up. The actuarial survival rates of all patients were 89 +/- 1% at 3 months, 68 +/- 2% at 6 months, 37 +/- 2% at one year, 12 +/- 1% at 3 years and 6 +/- 1% at 5 years; median survival was 9.1 +/- 0.4 months. Survival was significantly related to cancer size, tumor extension and surgical contraindications. In the Cox model, age, cancer size, surgical contraindications, year of diagnosis were independent prognostic predictors. There was a significant increase in survival rates after 1986: median survival was 8.1 +/- 0.4 months between 1984 and 1986 and 10.1 +/- 0.5 months between 1987 and 1988. Patients treated by curative resection had higher actuarial survival rates (median survival 22.5 +/- 4.1 months) than patients who underwent palliative resection (median survival 11.3 +/- 1.2 months). In patients with cancer managed surgically, the prognostic predictors were tumor size, curative vs palliative surgical resection and association with chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8467981 TI - [Toxic pollutants and fertility disorders. Solvents and pesticides]. AB - It is demonstrated by means of extensive reference studies, as well as own results, that organic solvents and pesticides can be accountable for intoxications and various complications during pregnancy (e.g. abortion, stillbirth, intrauterine growth retardation). An initial stimulation of the adrenal cortex (hyperandrogenaemia) can result in partial insufficiency of the adrenal cortex with symptoms like alopecia and feeling of sickness. Consequences can be hypo- and hyperthyroidism. The immunological system is affected (e.g. abortion, susceptibility to infections). Neurovegetative and neuropsychological concomitant symptoms are numerous. Toxic contaminants affect men at different levels of the semen producing organs (e.g. oligospermia, azoospermia). Indications regarding diagnosis of toxic substances related illnesses as well as therapeutic and prophylactic potentialities are presented. PMID- 8467982 TI - [Ambulatory surgery]. PMID- 8467983 TI - [Combined surgical and radiotherapeutic treatment of pelvic wall recurrences: report of experiences after 3 years]. AB - CORT has been developed to treat recurrent gynaecological malignancies infiltrating the pelvic wall unilaterally. The surgical part consists of: (i) staging laparotomy/lymphadenectomy, (ii) maximum tumour resection at the pelvic wall and exenteration of infiltrated central pelvic organs, (iii) implantation of guiding tubes on the residual tumour/tumour bed on the pelvic wall, (iv) pelvic wall plasty with muscle, musculocutaneous and omentum flaps, (v) operative reconstruction of bowel, bladder and perineo-vulvo-vaginal functions. Radiation is performed as interstitial high dose rate brachytherapy through the implanted tubes. Patients without prior pelvic irradiation receive in addition, whole pelvis teletherapy. CORT has been evaluated in a prospective phase I and II trial at the University of Mainz. Within a 3-year period, 21 patients with pelvic wall recurrences from various gynaecological primary tumours were treated. Seventeen patients had been irradiated as (part of) the previous therapy with a median total mid-pelvic dose of 65 Gy (range 40-100 Gy). There was no operative mortality. Five patients developed complications necessitating surgical intervention. One patient died from fatal thromboembolism 6 months after CORT without evidence of tumour progression. In 14 patients, local tumour control has been achieved. After a median follow-up period of 27 months (range 6-38 months) Kaplan-Meier life table analysis revealed an actuarial survival probability of 55% (recurrence-free 49%). We conclude from these preliminary results, that the CORT procedure for the treatment of pelvic wall recurrences is feasible and may lead to encouraging therapeutic success in selected patients, whose situation had been hopeless so far. PMID- 8467984 TI - [EGF receptor and EGF-like activity as prognostic factors in cervix cancer]. AB - The binding of the Epidermal Growth Factor (EGF) and the amount of EGF-like activity (EGF-A) was analysed in 75 cervical carcinomas and possible clinical implications were tested. EGF-A was significantly increased in patients with metastases to the pelvic and/or para-aortic lymph nodes. The EGF-receptor (EGF-R) capacity was inversely related to the histological grade (p < 0.05) and was reduced in highly differentiated tumours. In stage I and II disease, the clinical outcome was significantly reduced, if the receptor capacity or the level of EGF-A was increased (> 100 fmol/mg protein and > 0.5 ng/mg protein, respectively). The measurement of EGF-R capacity and EGF-A provides new and additional information for the prediction of the prognosis in cervical cancer. PMID- 8467985 TI - [The current status of prenatal diagnosis of myelomeningocele--results of a questionnaire]. AB - Questionnaires were sent to 1000 parents of children with myelomeningocele in order to get a better knowledge of the present state of prenatal diagnosis of this disease. 566 parents answered; 488 responders, in whom the pregnancy took place 1982 and later, were evaluated in detail. 85% of the parents reported having been checked by ultrasound 2 times and more during pregnancy: however, only 27% of the myelomeningoceles were detected before delivery. 83% were diagnosed between the 30th and 40th week of pregnancy. The rate of discovery rose from 0% and 37% between 1982 and 1990. As a consequence of this result, one should make every effort by using ultrasound and alpha-foetoprotein-screening to verify or to exclude a myelomeningocele in an early phase of pregnancy. The delivery should take place in a specialised centre, and the knowledge of life expectancy and life quality of these patients should be improved, for the obstetricians as well as for the parents. PMID- 8467986 TI - ["Facing"--a preliminary parameter in diagnosis of fetal skeletal abnormalities]. AB - Four cases with abnormalities of foetal faces are demonstrated--thanatophoric dwarfism, cheilognathopalotoschisis, osteogenesis imperfecta, achondrogenesis (Type I). A relationship to skeletal dysplasia was shown. We think, that the representation of foetal faces and their profile plays an important part in second trimester ultrasound screening between 18 and 22 weeks of gestational age. PMID- 8467987 TI - [Regular exercise therapy in disorders of carbohydrate metabolism in pregnancy- results of a prospective, randomized longitudinal study]. AB - Regular exercise has long been known as an adjunct in the therapy of diabetes mellitus. There are, however, only few reports on the impact of this therapy during pregnancy. This study aims at presenting an exercise programme for patients with insulin-requiring gestational diabetes (GDM) and its short-term and long-term effects on carbohydrate metabolism, on the foetus and on the course of pregnancy. Between the 26th and 32nd week of gestation, 41 pregnant subjects were randomised into either an exercise and diet group (EXE) or an Insulin and diet group (INS). The EXE patients (N = 21) trained three times per week at 50% VO2max. For 3 x 15 minutes on a recumbent bicycle ergometer throughout pregnancy with blood glucose monitoring before and after exercise). Blood glucose metabolism was followed by daily home monitoring and weekly fasting blood glucose sampling (FBG). The FBG results were comparable in the study and the control group (< 105 mg/dl); the maternal and foetal complications did not differ significantly between the two groups. The glycaemic parameters indicate a persistent decrease in blood glucose and an increase in insulin sensitivity induced by regular physical activity. We conclude, that such a medically supervised exercise programme can be safely conducted in women with GDM resulting in normoglycaemia for the mother and thus preventing insulin therapy. PMID- 8467988 TI - [Maternal and fetal morbidity and mortality in premature abruptio placentae--a retrospective analysis]. AB - The frequency of abruptio placentae has nearly tripled in our clinic since 1974 and now stands at 1.4% of all deliveries. In a retrospective analysis it was investigated whether improved diagnostic and therapeutic methods have decreased the morbidity and mortality of this severe obstetrical complication. During 3 stages of observation--1974-1979, 1980-1985 and 1986-6/1990--we registered 123 cases. The division into time intervals was based on the introduction of sensitive ultrasonic methods in 1980 and the vaginal scan in 1986. Important risk factors of abruptio placentae were found to be bleeding in pregnancy (32%), previous curettages (38%), premature labour (29%), and pre-eclampsia (14%). The diagnostic sensitivity of sonography rose from 40% in the first to 78% in the third interval of observation. The rate of vaginal deliveries decreased from 15% to 2%. Simultaneously, the perinatal mortality decreased, despite increasing foetal prematurity, from 30% to 2%. The improvement in foetal outcome could be demonstrated by 1- and 5-minute Apgar score values. During the entire period, we lost one mother with abruptio placentae complicated by fulminant lung embolism intra operationem. The frequency of serious stages of abruptio placentae (Page 2 3) decreased from 69% to 33%. While 54% of the mothers developed shock (shock index > or = 1) during delivery in the first observation period, this figure was finally only 10.5%. At the same time the frequency of coagulation disorders decreased from 31% to 4%. PMID- 8467989 TI - [Histiocytosis X (Langerhans cell granulomatosis) of the vulva]. AB - Isolated histiocytosis X (Langerhans cell granulomatosis) of the vulva is extremely rare. In most reported cases, vulval disease is associated with multitopic organ involvement. We report here on the second case in the world of isolated histiocytosis X of the vulva. The diagnosis could be established by immunohistochemical demonstration of anti-S 100 protein + Langerhans cells. The patient received a local radiation therapy of 10 gy and responded excellently. PMID- 8467990 TI - [Hereditary prolonged QT interval (Romano Ward syndrome) in obstetric management]. AB - In the Romano-Ward syndrome, an inherited form of abnormally prolonged QT duration is a matter for concern. The frequency-corrected QTc value in the ECG amounts to more than 0.44 s. Persons suffering from Romano-Ward syndrome are vitally endangered by attacks of arrhythmia, syncope and cardiac arrest which are triggered or aggravated by stress or certain drugs. In obstetrical anaesthesia, attention should be paid to the foetus, which, due to the genetic dominance, will have a 50% probability of suffering from the disorder. A 28-year-old para I was admitted with cervical dilation on her predetermined date of delivery. Romano Ward syndrome had been diagnosed 10 years earlier. The patient had been free of complaints and had received no treatment. Due to cephalopelvic disproportion and the cardiac syndrome, a primary Caesarean section was performed. The QTc values were pathologically prolonged (0.47 s; 0.48-0.63 s) during the pre- and intraoperative period. Haemodynamic irregularities did not occur in the perioperative period. The newborn was vital (3.830 g; 50 cm; Apgar scores 10/10/10; umbilical cord pH 7.29). Directly postpartum isolated supraventricular extra systoles occurred, and the QTc duration increased to 0.51 s. PMID- 8467991 TI - [Rudolf Kaltenbach. On the 150th anniversary of his birth and 100th anniversary of his death]. PMID- 8467992 TI - Non-specific hole formation in the Escherichia coli inner membrane by lambda S proteins in independent of cellular secY and secA functions and of the proportion of membrane acidic phospholipids. AB - Formation of the lesion in the Escherichia coli inner membrane caused by lambda lysis protein S was examined by electron microscopy. We also show that macromolecules exceeding the size of the lambda R transglycosylase can pass through the S-dependent hole and that assembly of the S-dependent hole is independent of the proportion of acidic phospholipids in the inner membrane and of components of the cellular transport machinery. PMID- 8467993 TI - Purification of a fibroblast-inhibitory factor from Actinobacillus actinomycetemcomitans Y4. AB - A factor showing inhibitory activity against human gingival fibroblasts was extracted from the cytosol fraction of Actinobacillus actinomycetemocimitans Y4. The activity markedly inhibited the proliferation of human gingival fibroblasts, but had no effect on cell viability or gross morphology. No such activity was found in cytosol fractions from either Porphyromonas gingivalis 381 or Escherichia coli HB101. The extract from A. actinomycetemocomitans Y4 was then purified by anion-exchange chromatography, hydroxyapatite chromatography and gel filtration chromatography to give a single band on SDS-PAGE with an apparent molecular mass of 65 kDa. The purification ratio was 183-fold with a recovery rate of 5% compared with the crude extract (starting material) when the activity was assessed by direct cell counts. PMID- 8467994 TI - Heme b (protoheme IX) is a precursor of heme a and heme d in Bacillus subtilis. AB - Bacillus subtilis can synthesise cytochromes containing a-, b-, c- and d-type heme. The biosynthetic pathways of these heme prosthetic groups were investigated by using strains blocked in uroporphyrinogen III synthesis from porphobilinogen or in heme b (protoheme IX) synthesis from uroporphyrinogen III. The results strongly suggest that heme a and heme d are both synthesised from heme b (protoheme IX). They also indicate that B. subtilis contains a novel ferrochelatase involved in the synthesis of siroheme. PMID- 8467995 TI - Alternate interactions of the D-galactose-specific yeast lectin Kb-CWL I with sensitive yeast strains. AB - In vitro growth assays with a purified D-galactose-specific lectin Kb-CWL I extracted from Kluyveromyces bulgaricus showed marked antifungal effects on 9 of 12 test strains belonging to the genera Kluyveromyces, Saccharomyces, Pichia, Candida, Rhodotorula and Schizosaccharomyces. The inhibition of growth was proportional to the lectin concentration (0.04 and 0.08 mg ml-1) in the culture medium. Under the test conditions, K. bulgaricus, K. lactis and S. bayanus were consistently agglutinated without growth inhibition. D-Galactose, the inhibitory sugar of the cell aggregation activity, did not abolish the antifungal effects of the lectin Kb-CWL I on other yeast strains tested. In C. albicans and C. tropicalis, the lectin influenced the dimorphism of these strains and stimulated germ tube formation. PMID- 8467997 TI - Microbial desulfurization of dibenzothiophene: a sulfur-specific pathway. AB - Rhodococcus rhodochrous strain IGTS8 metabolizes dibenzothiophene, a model compound for organic sulfur in fossil fuels, in a sulfur-specific manner. Two routes of desulfurization have been identified. Under growth conditions, the intermediates are dibenzothiophene sulfoxide, dibenzothiophene sulfone, 2' hydroxybiphenyl-2-sulfonate, and 2,2'-dihydroxybiphenyl. Stationary phase cells produce 2-hydroxybiphenyl as the desulfurized product and use the 2' hydroxybiphenyl-2-sulfinate, rather than the sulfonate, as the key intermediate. PMID- 8467996 TI - A yeast gene for trehalose-6-phosphate synthase and its complementation of an Escherichia coli otsA mutant. AB - A Saccharomyces cerevisiae gene for trehalose-6-phosphate synthase (TPS1) was sequenced. The gene appeared to code for a protein of 495 amino acid residues, giving the protein a molecular mass of 56 kDa. The TPS1 gene was able to restore both osmotolerance and trehalose accumulation during salt stress in an Escherichia coli strain mutated in the otsA gene encoding trehalose-6-phosphate synthase. Complementation studies with E. coli galU mutants showed that the TPS1 encoded trehalose-6-phosphate synthase is UDP-glucose-dependent. Sequence analysis and data base searches showed that TPS1 is allelic to GGS1, byp1, cif1 and fdp1. A possible gene for trehalose-6-phosphate synthase in Methanobacterium thermoautotrophicum was identified. PMID- 8467998 TI - Screening of thermotolerant yeasts as producers of superoxide dismutase. AB - A screening procedure for highly thermostable yeast superoxide dismutase was developed. Growth yields at various temperatures were estimated for ten mesophilic and thermotolerant strains, belonging to the genera Saccharomyces, Kluyveromyces and Pichia. Higher yields at 45 degrees C were obtained for K. lactis 90-3 and 90-4. A correlation between the ability to grow at higher temperature and the thermostability of the superoxide dismutase enzyme synthesized was observed. A comparison of the operational stability of the superoxide dismutase of all tested strains suggests that the enzyme of K. lactis strains was more thermostable than that of the other tested microorganisms. PMID- 8467999 TI - Production and characterisation of a Legionella pneumophila specific monoclonal antibody. AB - To better define the antigenic structure of the outer cell membranes of Legionellae, a panel of 6 monoclonal antibodies was raised against partially purified outer membranes of Legionella pneumophila serogroup 1, Corby strain. This study describes the purification and characterization of one of these monoclonal antibodies reacting with a 135-kDa protein, which was shown to be common to all 14 serogroups of Legionella pneumophila. It shows no cross reactivity with 20 other Legionella species, or 9 other Gram-negative species tested by SDS-PAGE and Western blotting procedures. The epitope would appear to be predominantly surface exposed and, from preliminary detergent extraction studies, not peptidoglycan-associated. PMID- 8468000 TI - Cloning and partial sequence of transferrin-binding protein 2 of Neisseria meningitidis using a novel method: twin N-terminal PCR. AB - The genes encoding transferrin-binding proteins (TBPs) 1 and 2 of Neisseria meningitidis and N. gonorrhoeae were used as model loci in a novel method of cloning (twin N-terminal polymerase chain reaction; TNT-PCR) involving amplification between the 5' ends of two genes. Primers were based on N-terminal amino-acid sequences. A 2.1-kb product amplified from N. meningitidis strain SD (B15 P1.16) was cloned into a plasmid vector and partially sequenced. Translated sequence immediately downstream of the primer at both ends of this product correlated to the additional known N-terminal amino acids of TBP-1 and 2. The protein encoded by the cloned sequence reacted with TBP-2-specific antiserum. The size of products generated in TNT-PCR correlated exactly with the different sized TBP-2 produced by 10 strains of the Neisseria spp. examined, indicating successful cloning of the gene for TBP-2 and showing it to be adjacent to and preceding TBP-1 on the chromosome for both N. meningitidis and N. gonorrhoeae. PMID- 8468001 TI - Identification of Streptococcus mutans antigen D as the HPr component of the sugar-phosphotransferase transport system. AB - Extraction of Streptococcus mutans with the detergents HECAMEG and lauroyl sarcosinate preferentially extracted antigen D, previously identified as a low molecular mass wall-associated protein. Western blotting with specific antisera was used to demonstrate that this antigen is the HPr component of the sugar phosphotransferase transport system. Non-denaturing electrophoresis indicated that HECAMEG selectively extracted only one of the two forms of HPr. It is suggested that this form of HPr may have a specific cell surface location. PMID- 8468002 TI - Temperature-sensitive amber suppression of ompF'-'lacZ fused gene expression in a supE mutant of Escherichia coli K12. AB - In an ompF'-'lacZ fusion system carried by the open reading frame vector pORF1 in a supE mutant of Escherichia coli K12, read-through of an amber codon was decreased at temperatures higher than 40 degrees C. This effect of temperature was dependent on the nucleotide sequence surrounding the amber codon, which was inserted into a site between the ompF and lacZ cistrons. Upon a temperature shift up from 30 to 42 degrees C, beta-galactosidase synthesis directed by this fusion showed a transient arrest. PMID- 8468003 TI - Surface hydrophobic and hydrophilic protein alterations in Candida albicans. AB - Cell surface hydrophobicity influences pathogenesis of Candida albicans. Previous studies suggested that stationary-phase hydrophilic and hydrophobic cells, obtained by growth at 37 and 23 degrees C, respectively, may have similar hydrophobic proteins. However, whether hydrophilic and hydrophobic surface proteins differ during the growth cycle at 37 degrees C is unknown. Freeze fracture analysis revealed surface fibrillar layer differences between hydrophobic late-lag and hydrophilic stationary-phase yeast cells grown at 37 degrees C. Hydrophilic protein differences were also observed between these populations. However, similar hydrophobic proteins were detected among the late lag and stationary phase cells grown at 37 degrees C and hydrophobic stationary phase cells grown at 23 degrees C. These results suggest that hydrophobic proteins remain constant but hydrophilic proteins vary during growth. Thus, conversion from surface hydrophilicity to hydrophobicity by C. albicans may only require alterations in the hydrophilic fibrillar protein components. PMID- 8468004 TI - Effect of the anti-microtubule compound tubulozole on Leishmania protozoan parasites in vitro. AB - For the cis and trans stereoisomers of the synthetic anti-microtubule compound tubulozole, at micromolar concentrations, tubulozole-C is cytotoxic to mammalian cells whereas tubulozole-T is not. The effect of tubulozoles on the parasitic protozoan Leishmania was tested. For the promastigote stage of L. mexicana amazonensis, both isomers inhibited parasite growth. For the amastigote stage of L. mexicana amazonensis and L. major, within murine J774 macrophage line as host cells in vitro, tubulozole-T reduced the infective index. Despite the observation of macrophage cytotoxicity of tubulozole-T, this compound may be a potentially useful and novel anti-leishmanial drug. PMID- 8468005 TI - Expression of the Escherichia coli ftsZ gene: trials and tribulations of gene fusion studies. AB - The ftsZ gene of Escherichia coli, which codes for an essential cell division protein, is subjected to multiple regulation, as shown in part with studies using an ftsZ::lacZ operon fusion located on phage lambda JFL100. Using this same fusion, we sought to isolate regulatory mutants overexpressing ftsZ by selecting mutants able to grow on lactose. One Lac+ mutant was obtained which overexpressed the ftsZ::lacZ fusion 70-fold. The mutation responsible for the overexpression lies in a new gene, cot, located near 56 min on the E. coli genetic map. The cot mutation probably affects the transcription of a chromosomal open reading frame, ORF1, lying downstream of the bioA gene and adjacent to the ftzZ::lacZ fusion of the lambda JFL100 prophage integrated at att lambda. Using an ftsZ84(Ts) strain, in which there was a double selection for overexpression of both ftsZ::lacZ and ftsZ+, no Lac+Tr mutants were obtained from 3.6 x 10(10) bacteria; the introduction of a mutL allele, increasing spontaneous base substitution mutation rates 75-fold, did not permit us to isolate such a mutant. We conclude that Lac+ ftsZ-constitutive mutations cannot be obtained in lambda JFL100 lysogens by a single base substitution. PMID- 8468006 TI - Studies of linkage in populations. X. Altitude and autosomal gene arrangements in Drosophila robusta. AB - Data are presented concerning the gene arrangements in the second and third chromosomes of Drosophila robusta in eight altitudinal transects. A consistent change is the increase in the arrangement 2L-3, particularly in the linkage combination 2L-3.2R, with increasing altitude. The reciprocal decrease with increasing altitude affects several different 2-left arrangements, most consistently 2L-1. The arrangements of 2-right show no significant variation with altitude, and those of 3-right do so only in a few samples of the two northern transects studied, none in any of the southern ones. These results confirm previous evidence for the significant role of the arrangements of the left arm of the second chromosome in the adaptations of this species to altitude and suggest further that interactions of linked arrangements are involved in these adaptations. The data also indicate that the factors responsible for the altitudinal adaptations of this species are in many cases not the same ones that are responsible for variations in its gene arrangements with latitude. PMID- 8468007 TI - Continuity after a stroke: implications of life-course disruption in old age. AB - Life-course disruption caused by a stroke and subsequent attempts on the part of stoke victims to restore continuity was explored through qualitative research with a sample of 216 persons. This research suggests: 1) that theory in gerontology could be deepened by framing continuity to include discontinuous experience in late life; and 2) that research on what elderly persons themselves make of continuity--how they perpetuate it or recreate it and the obstacles they perceive in doing so--may inform our understanding of the experience of old age and lead to applications in the practice of gerontology that address the disruption illness poses for people's lives. PMID- 8468008 TI - Adopting a disability approach to home care services for older adults. AB - The disability and aging communities differ significantly in their perceptions, definitions, and values about the independence and autonomy of disabled individuals. These viewpoints are reflected in the different services and goals of personal assistance provided to older and younger disabled persons. We explore the applicability of the disability approach to personal assistance for older persons and offer ethical, practice-oriented, and political arguments for the aging community to adopt this approach. We also review past efforts toward achieving a "unified agenda" between the aging and disability communities and outline possible future initiatives. PMID- 8468009 TI - Changes in the use of personal assistance and special equipment from 1982 to 1989: results from the 1982 and 1989 NLTCS. AB - Analysis of data from the 1982, 1984 and 1989 National Long-term Care Surveys suggests that long-term care use is changing. Between 1982 and 1989, equipment use by persons with light physical impairment, or to supplement personal assistance for the severely disabled, increased. Over this same period, there was a decline in the use of personal assistance as the sole modality to deal with chronic impairments. Since equipment costs are nonrecurrent, whereas personal assistance costs are recurrent, this finding has implications for long-term care policy. PMID- 8468010 TI - The cost-effectiveness of community services in a frail elderly population. AB - We use an integrated model incorporating simple principles of decision analysis and marginal cost analysis to discuss cost-effectiveness of community long-term care services as a substitute for nursing home care. By taking individuals as the unit of analysis and analyzing different types of community services separately, the model defines the targeting issue precisely and permits key policy parameters to be estimated empirically. When applied to data from the National Long Term Care Channeling Demonstration, 41% of those screened into the control group were found to have some potential for net long-term care cost reduction through program services. PMID- 8468011 TI - State units and convergence models: needs assessment revisited. AB - Based on a comprehensive survey of state and territorial units on aging, this article reexamines and evaluates the needs assessment process in place in social service agencies. Although most agencies reported multiple sources of planning data, serious limitations in the representativeness of selected data sets were still apparent. We outline a convergence model of needs assessment that utilizes a long-range planning perspective for the development of planning models. PMID- 8468012 TI - Falls in dementia patients. AB - We analyzed the number and nature of falls in a nursing home for elderly patients with dementia. Staff reported 1,343 falls over a 2-year period in 240 patients, a rate of about 4 falls per person year. The risk of falling was especially high shortly after admission and after transfer to another ward, increased with severity of the dementia and physical impairment, and decreased for very severely demented or physically handicapped patients. Men had twice the risk of falling of women. Most incidents were relatively harmless, but 33 fractures were reported. The most common causes for falls were "inadequate (use of) materials, stumbling, or slipping" (17%) and "gait and equilibrium disturbances" (16%). PMID- 8468013 TI - The perspective of the patient with Alzheimer's disease: a neglected dimension of dementia research. AB - The patient perspective has been largely ignored in studies of Alzheimer's disease. The person with dementia is often relegated to the status of object rather than legitimate contributor to the research process and much can be gained from a systematic study of patients' views regarding their illness and care. We examine the status of dementia patients in three research areas and identify research challenges and opportunities that may substantially increase our understanding of dementia. PMID- 8468015 TI - Volunteerism by elders: past trends and future prospects. AB - A number of surveys indicate a rise in the percentage of elders involved in volunteer work over the past 25 years. This article identifies cultural, demographic, and programmatic factors that have contributed to this increase. After describing some current policies and programs, it identifies strategies for sustaining and expanding volunteerism by elders in the future. PMID- 8468014 TI - Amenity retirement migration process: a model and preliminary evidence. AB - A heuristic model of the retirement migration process was developed and explored using survey data from 586 migrants to western North Carolina. Five distinct subgroups were investigated: those who went from part- to full-time residency; those who thought about not migrating; individuals who migrated, remained in the labor force for a short period, and then retired; people who made two retirement migrations; and destination-selecting versus destination-specific migrants. PMID- 8468016 TI - The effects of caregiving on women's Social Security benefits. AB - Using data from the Social Security Administration's 1982 New Beneficiary Survey, we tested a life-course model that suggests that early- and late-life caregiving reduce monthly Social Security benefits of newly retired women workers. Each child raised was associated with a loss of $8 to $16 dollars in the 1983 Social Security primary insurance amounts (PIAs). The 1983 PIAs of women leaving their last jobs to care for others were $127 lower than the PIAs of women who left because of the availability of Social Security benefits, to receive a pension, or because they wanted to retire. Leaving work to care for others exerted a stronger depressing effect on the Social Security benefits of women with low- and moderate as opposed to high-earnings histories. PMID- 8468017 TI - A meta-analytic review of interventions for caregiver distress: recommendations for future research. AB - This review summarizes articles from 1980 to 1990 on psychosocial interventions and respite care for caregivers. The review was limited to controlled studies that attempted to change emotional distress in caregivers. Cumulatively, they suggest that individual psychosocial interventions and respite programs are moderately effective; psychosocial interventions with groups are less so. PMID- 8468018 TI - Depressive symptoms in family caregivers of long-stay patients. AB - Factors contributing to depressive symptoms in a group of 67 family caregivers of hospitalized "long-stay" patients were investigated. Levels of depressive symptoms were quite high and were related to level of patient dependency, caregiver's health, feeling too many demands were being made on the caregiver, feeling torn between the patient's needs and the caregiver's own needs, not getting enough rest, amount of time spent in caregiving activities, feeling someone else could take over caregiving if necessary, and perceptions of staff. The factors contributing to depressive symptoms differed among spouses, children and other caregivers, but for all the strongest contributor was experiencing difficulty with staff. PMID- 8468019 TI - A task-specific typology of intergenerational family structure in later life. AB - We tested a typology of intergenerational social support structure with data from 910 dyads of older adults and their primary child helpers. Logistic regression was used to identify variables that differentiate dyads with distinct support configurations. Household support provided to elderly parents was more sensitive to physical and social deficits and geographic distance, whereas social-emotional support was more sensitive to norms and personal affinity. PMID- 8468020 TI - Using an imaginary scrapbook for neurolinguistic programming in the aftermath of a clinical depression: a case history. AB - We employed neurolinguistic programming (NLP) principles to develop a positive self-identity in an elderly male patient in England recovering from clinical depression. This novel technique encouraged recall of intrinsically rewarding past experiences. Each experience was conceptualized in an image and compiled chronologically in an imaginary book, providing continuity to what were chaotic and fragmented recollections during the immediate postdepressive stage. The patient's anxiety and depression were alleviated and his own functional goals largely realized. PMID- 8468021 TI - A center on ethics in long-term care. AB - Long-term care institutions are beginning to grapple with ethical issues on a regular basis. This has encouraged facilities to develop new mechanisms to deal with these issues. Described is a tripartite program that incorporates direct service, education, and research in ethics. PMID- 8468022 TI - Cytostatic effects of horseradish and thyroid peroxidase derived free radicals. AB - An otherwise noncytostatic flux of H2O2 from glucose and glucose oxidase became cytostatic to cultured Chinese Hamster Ovary (CHO) cells when horseradish or thyroid peroxidase was added to the culture medium. Electron spin resonance (ESR) measurements showed that one or more factors present in the culture medium promote the one-electron oxidation of a reduced nitroxide or glutathione in an H2O2/peroxidase-dependent process. Moreover, a reduced nitroxide conferred significant protection against the cytostatic effect of H2O2/peroxidase. Cytostatic effects were not only seen in the presence of the active H2O2/peroxidase system, but also in media which had been preexposed to H2O2/peroxidase but no longer contained an active H2O2 generating system. It is suggested that peroxidases oxidize one or more factors in tissue culture media to free radicals, which react with nearby components of cells or form toxic products, causing growth inhibition. If similar free radical precursors are present in tissue fluids, some of the toxicity of H2O2 in vivo may be due to peroxidase-mediated endogenous free radical generation. PMID- 8468023 TI - Diphenylamine: an unusual antioxidant. AB - Diphenylamine (DPA) has been utilized as an antioxidant in studies of lipid peroxidation. Using peroxidizing red blood cell (RBC) membranes, we find that DPA actually promotes lipid hydroperoxide (LOOH) formation and oxygen consumption while markedly inhibiting generation of thiobarbituric acid reactive substances (TBARS). As a consequence, DPA increases the prelytic RBC K leak that results from peroxidative stress and potentiates a known nonprelytic but LOOH-dependent K leak pathway in RBC. In contrast, DPA abolishes formation of cyclooxygenase dependent conversion products of arachidonate. DPA is almost as efficient as BHT in inhibiting peroxyl radical mediated destruction of phycoerythrin fluorescence. Study of DPA analogues shows that the antioxidant effect of DPA lies in its secondary amine function. Presumably, this results in intermediate formation of a nitrogen-based radical so that redox cycling of this aromatic amine stimulates further peroxidation. This dramatically illustrates the hazard of relying solely on TBARS measurements for assessment of peroxidation. PMID- 8468024 TI - Lipid hydroperoxides potentiate mesenteric artery vasoconstrictor responses. AB - The aim of this study was to investigate the effects of lipid and organic hydroperoxides on vasomotor activity of isolated rat superior mesenteric arteries. Hydroperoxides did not elicit measurable responses in unstimulated (quiescent) mesenteric arteries. Contractile responses to potassium, however, were significantly potentiated by 13-(s)-hydroperoxylinoleic acid (range 3-54 microM). Potentiation of potassium responses by linoleic acid (18:2) and linolenic acid (18:3) was increased by pretreatment of the fatty acids with lipoxygenase (p < .01). Lipoxygenase alone had no contractile effects. Lipoxygenase-treated 18:2, tert-butyl hydroperoxide, and hydrogen peroxide augmented contractile responses to phenylephrine, but to a lesser degree than corresponding augmentation of potassium responses. Contractile responses to lipoxygenase-treated 18:3 were blunted by vitamin E (p < .02) and by nitroblue tetrazolium (p < .02), whereas catalase and mannitol had no effects, implicating lipid free radicals in the contractile response. Responses to lipid hydroperoxides were not significantly altered by prostaglandin inhibitors. Endothelial cell denudation significantly enhanced the contractile responses elicited by 13-(s)-hydroperoxylinoleic acid (p < .05), indicating that lipid hydroperoxides enhance agonist-induced contractions by a direct effect on the smooth muscle. These results support a hypothesized link between lipid peroxidation and development of altered vascular function. They further suggest that the vascular endothelium may play an important role in regulation of vasomotor responses to lipid hydroperoxides. PMID- 8468025 TI - Antioxidant enzyme activities in IDD-prone and IDD-resistant mice: a comparative study. AB - Insulin-dependent diabetes (IDD) in the nonobese diabetic (NOD) mouse is believed to result from the specific autoimmune destruction of pancreatic beta cells. The frequency of diabetes in the NOD mouse is sex-dependent, with approximately 90% of females and 40% of males developing clinical diabetes by 40 weeks of age. Recently, attention has focused on determining possible mechanisms for beta cell destruction. One potential mechanism is the toxic effect of free oxygen radicals produced as a result of the influx of inflammatory cells into the pancreas. A deficiency in available antioxidant enzymes could form a basis for diabetes susceptibility. To test the feasibility of this idea, we have compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in isolated islets, pancreas, and other tissues of age- and sex-matched NOD, BALB/c, C57BL/10, and B10.GD mice. Enzyme profiles revealed that female NOD mice do not differ significantly in antioxidant enzyme activity from females of the other inbred strains. However, antioxidant enzyme activity in females was generally lower than in males regardless of mouse strain. While isolated islet cells exhibited somewhat lower levels of enzyme activity than other tissues, the islets of NOD mice proved to be no more deficient than those of BALB/c mice. Therefore, it is unlikely that any toxic effect of free oxygen radicals on the beta cells of NOD mice results directly or solely from an antioxidant enzyme deficiency. Nevertheless, one possible explanation for the lower incidence of diabetes in NOD males versus females may be the inherently higher male antioxidant enzyme activities. PMID- 8468026 TI - Evidence that the large loss of glutathione observed in ischemia/reperfusion of the small intestine is not due to oxidation to glutathione disulfide. AB - Reperfusion injury following ischemia is thought to be the consequence of reactive oxygen species possibly generated either by xanthine oxidase activity or by processes associated with neutrophil activation in the affected organ or tissue. The conversion of xanthine dehydrogenase to the oxidase as well as the interactions between endothelium and neutrophils in the margination and activation of the latter are all considered to be results of conditions resulting from the ischemic episode. Determination of the redox status of glutathione in an ischemic/reperfused organ is frequently employed as an indicator of oxidative stress created by the production of oxygen free radicals during the reperfusion period. In this procedure, the ratio of oxidized glutathione (GSSG) to total glutathione (GSH + GSSG) is utilized to demonstrate the proportion of glutathione oxidized during reperfusion. We determined this ratio in the rat small intestine during ischemia and reperfusion and found that while the ratio of GSSG/(GSH + GSSG) does increase, this increase was the result of GSH disappearance rather than an increase in GSSG, and that essentially all of this loss occurred during the ischemic episode. We demonstrated that no oxidation of GSH occurred that was attributable to reperfusion per se; nor was there an increase of GSSG during this reoxygenation period. PMID- 8468027 TI - Free radicals and calcium homeostasis: relevance to malignant hyperthermia? AB - The regulation of intracellular free calcium ions (Ca2+) in skeletal muscle at rest and during contraction depends on mechanisms such as Na(+)-Ca2+ exchangers, Ca(2+)-ATPases, and the voltage-sensitive ryanodine receptor. The susceptibility of these regulatory mechanisms to free-radical-mediated damage may be increased because of their location within the lipid membranes of sarcolemma, sarcoplasmic reticulum, and mitochondrion with resultant uncontrolled increases in myoplasmic Ca2+ concentration and cell death. The potentially fatal pharmacogenetic disorder, malignant hyperthermia (MH), is characterised by muscle rigidity, arrhythmias, lactic acidosis, and a rapid rise in body temperature. The sequence of events responsible for the MH syndrome remains uncertain, but it has been variously ascribed to faults in many of the Ca2+ regulatory mechanisms. In swine the condition is associated with a specific mutation in the ryanodine receptor, whereas in humans the syndrome is genetically heterogenous. Free-radical-mediated peroxidation of membrane lipids and proteins also results in the rapid efflux of Ca2+ from organelles, and the detection of products of free radical reactions in tissue from MH-susceptible individuals using electron spin resonance spectroscopy provides evidence for the involvement of free radicals in the MH syndrome. PMID- 8468028 TI - Ozone exposure inhibits cardiac protein synthesis in the mouse. AB - Ozone is a major environmental oxidant pollutant. Following ozone inhalation, there are a number of marked pulmonary responses depending on the extent and duration of exposure. Recently it has been established that ozone exposure may also result in cardiac injury. In this study we show that exposure of mice to 800 ppb ozone for as little as 6 h results in a 16% decrease in cardiac protein synthesis rates (p < .02). The fall in protein synthesis is due primarily to a reduced rate of ribosomal efficiency (40%) in the hearts of ozone-exposed mice. This change in cardiac protein metabolism is accompanied by increased levels of two markers of tissue injury: edema and protein carbonyl content. It is unlikely, however, that these observations represent a direct action of ozone on the heart, but rather an indirect effect, possibly mediated by lipid peroxidation products generated in the lung. PMID- 8468029 TI - [Perioperative preventive use of antibiotics]. PMID- 8468030 TI - Significance of animal studies for perinatal research. AB - Only recently has it been possible to access human fetuses to obtain blood samples in utero, and to monitor circulatory dynamics by ultrasound. Most of our knowledge of fetal physiology and metabolism has been derived from animal studies. Using techniques of chronic implantation of intravascular catheters and specialized methods for measuring organ blood flow, cardiac output, and vascular pressures, much has been learned about normal fetal vascular physiology and its responses to stress. In addition, it has been possible to simulate abnormal morphology and to examine its effects on fetal function. Caution should be exercised in directly relating information obtained from animal studies to the human fetus. Differences in maturity at the time of birth, and in morphology, such as relative brain to body weight, must be taken into consideration. PMID- 8468031 TI - Umbilical artery flow velocity waveform analysis and assessment of fetal oxygenation. AB - Assessment of the fetal condition is an important but also difficult problem. During the last decades a number of new fetal monitoring techniques have been introduced into clinical practice without proper evaluation regarding its value for clinical practice beforehand. The last fetal monitoring technique introduced into clinical practice in such a way is the assessment of the fetal condition with umbilical artery flow velocity waveform analyses. Although in cases with zeroflow or reverse flow during diastole the complication rate is high, it is not possible to assess the fetal oxygenation by means of recording the umbilical artery pulsatility index and its changes. Moreover no adequate treatment of fetal hypoxia is yet available, except termination of pregnancy. It is important in this context to realize that prematurity in itself is still the most powerful determining factor for the further development of the child. PMID- 8468032 TI - [Clinical etiologies in fetal hypoxia in pregnancy]. PMID- 8468033 TI - Uterine contractions and their possible influence on fetal oxygenation. AB - There is now ample evidence that during uterine contractions the utero-placental blood flow diminishes leading to a temporary decrease of fetal oxygenation. Although the fetus lives at a body temperature of 38 degrees Celsius, the adaptive mechanisms seem to be well attuned to sustain this relative oxygen deprived situation during pregnancy and also during labour. Nevertheless in clinical obstetrical practice the fetus can dy in utero or survive with neurologic handicaps. This is a rare event in term low risk babies with a bodyweight appropriate for gestational age (AGA) in contrast to obstetrical pathology that can jeopardize especially infants small for gestational age (SGA). PMID- 8468034 TI - [The fetal cardiovascular reaction to acute and chronic hypoxia]. PMID- 8468035 TI - [Circulation and energy supply to the fetal brain in hypoxia: relation to early childhood brain damage]. PMID- 8468036 TI - [Effects of fetal hypoxia on later life. Late prognosis of asphyxia neonatorum]. PMID- 8468037 TI - [The significance of perinatal data for perinatal research]. PMID- 8468038 TI - [Importance of technical advances for CTG monitoring in the near future]. PMID- 8468039 TI - [Physiologic and biochemical mechanisms of O2 supply of the fetus]. PMID- 8468040 TI - Identification and partial characterization of a candidate gene for X-linked retinopathies using a lateral approach. AB - Using library to library cross-screening we have identified a number of genomic clones that harbor X-linked sequences expressed in the human choroid/retina. We describe the characterization of one of these, designated XEH.8 (DXS542), which is localized to Xp11.3-q12. Isolation, partial sequencing, and Northern analysis of the cognate cDNA (XEH.8c), has shown that the cDNA has some homology to the dystrophin gene and hybridizes to a 10-kb mRNA present in the choroid and retina but not in fibroblasts. This expressed sequence maps to the same region of the X chromosome as several known X-linked ophthalmic diseases, including Norrie disease, retinitis pigmentosa 2, congenital night blindness and Aland Island eye disease. PMID- 8468041 TI - Key features of cereal genome organization as revealed by the use of cytosine methylation-sensitive restriction endonucleases. AB - Unlike mammalian genomes, cereal (Gramineae) genomes exhibit little suppression of CpG dinucleotides. In cereal genomes, however, most of the numerous potential recognition sites for CpG methylation-sensitive restriction enzymes are methylated. Analysis of cereal genomic libraries and of regions flanking genes indicates that unmethylated NotI sites are useful landmarks for regions containing genes/single-copy sequences. Studies of a rye chromosome arm indicate that its pericentromeric region has a reduced density of unmethylated NotI (and MluI) sites and therefore of genes. Unmethylated MluI and NruI sites are distributed nonrandomly in the genomes of wheat, barley, and rice. Analysis of the genomic blocks defined by these sites in wheat and barley indicates that they are most likely to have arisen by amplification. These observations form the basis of a proposed model for the organization and evolution of the wheat, barley, and rice genomes. PMID- 8468042 TI - Novel sequences conserved on the human and mouse X chromosomes. AB - We have cloned and mapped 28 single-copy probes from a pool of cosmids derived from the human X chromosome. Four of the probes detected strongly conserved sequences in murine DNA; all have been localized to the proximal region of the human X chromosome short arm. Comparative mapping of these sequences in the mouse genome demonstrates that, while X linkage is conserved, this region of the human X chromosome is not maintained as a contiguous segment on the mouse X chromosome. The mapping of one novel conserved sequence between Plp and Pdha1 on the mouse X chromosome defines a previously unknown region of homology. The mapping of another probe that detects a novel sequence family (DXF34) close to the X chromosome centromere in both species suggests that a block of pericentromeric material is conserved between the X chromosomes of man and mouse. PMID- 8468043 TI - Isolation and mapping of human chromosome 21 cosmids using a probe for RTVL-H retrovirus-like elements. AB - We have explored the usefulness of a cloned low-repetitive DNA element, termed RTVL-H, for the region-specific isolation of DNA cosmids from chromosome 21. Hybridization of the RTVL-H element as a probe to genomic Southern blots of DNAs from a chromosome 21-specific somatic cell hybrid panel demonstrated the presence of at least seven RTVL-H-related sequences in defined regions dispersed over the chromosome. Some of the RTVL-H sequences detected by using the chromosome 21 specific somatic cell hybrid panel were subsequently isolated from a chromosome 21-specific cosmid library and mapped using somatic cell hybrids. In general, close correspondence was found between mapping results obtained using the consensus RTVL-H probe on the chromosome 21-specific somatic cell hybrid panel and the more precise mapping obtained using cosmids. The results demonstrate that sequences such as the RTVL-H element can be used for isolating region-specific sequences. PMID- 8468044 TI - Deletion mapping and a highly reduced radiation hybrid in the Xp22.3-p22.2 region. AB - The human Xp22.3-p22.2 region contains several known disease genes as well as distinctive families of low copy repetitive sequences. In this study, we have developed new tools to more finely map this area. We have characterized a mapping panel of various cell lines and hybrids with different molecular breakpoints as defined by previously mapped reference markers from this region. The panel subdivides this area into nine distinct regions from DXS41 through the pseudoautosomal boundary. We have also identified a radiation-reduced somatic cell hybrid, Z4-7, that contains DXS31, DXS452, STS, DXS143, and DXS85, but not PABX, DXS16, or other single-copy probes from proximal Xp and Xq. A phage library was constructed from Z4-7 and over 80,000 plaques were screened with total human DNA. More than 100 positive clones were identified as potential new markers in this region. Nine of these have been mapped to the hybrid panel, and unique subclones have been isolated from three of these markers. The panel has also allowed us to map several other DNA markers, genes (AMG, OA1), and repetitive elements of the DXF22S and DXF30S sequence families relative to the various breakpoints. PMID- 8468045 TI - Molecular characterization and mapping of murine genes encoding three members of the stefin family of cysteine proteinase inhibitors. AB - Stefins or Type 1 cystatins belong to a large, evolutionarily conserved protein superfamily, the members of which inhibit the papain-like cysteine proteinases. We report here on the molecular cloning and chromosomal localization of three newly identified members of the murine stefin gene family. These genes, designated herein as mouse stefins 1, 2, and 3, were isolated on the basis of their relatively increased expression in moth-eaten viable compared to normal congenic mouse bone marrow cells. The open reading frames of the stefin cDNAs encode proteins of approximately 11.5 kDa that show between 50 and 92% identity to sequences of stefins isolated from various other species. Data from Southern analysis suggest that the murine stefin gene family encompasses at least 6 and possibly 10-20 members, all of which appear to be clustered in the genome. Analysis of interspecific backcross mice indicates that the genes encoding the three mouse stefins all map to mouse chromosome 16, a localization that is consistent with the recent assignment of the human stefin A gene to a region of conserved homology between human chromosome 3q and the proximal region of mouse chromosome 16. PMID- 8468046 TI - Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family. AB - For a better understanding of genes that potentially function in B lymphocyte cell signaling, we isolated the human genomic counterpart of the murine pp52 or LSP1 gene. We unexpectedly found that the human pp52 gene is one of four closely related loci. Representative cosmids from each of the four family members were isolated and chromosomally localized by fluorescence in situ hybridization. Nucleotide sequence was obtained from an exon common to each locus and demonstrated very close similarity among all four loci. Two of the four loci harbored dysfunctional frameshift mutations or premature translation stop sites. The exon of one locus was flanked by an 80-bp perfect inverted repeat, suggesting that it may have originated through a looped intermediate DNA structure. Through a series of cDNA hybridization studies and nucleotide sequence analyses we were able to unambiguously link the lymphocyte-expressed gene to the locus mapped to chromosome 11p15.5. This same chromosomal band has been involved in tumor-related chromosomal translocations found in chronic lymphocytic leukemia. PMID- 8468047 TI - High-resolution chromosomal localization of the human calcitonin/CGRP/IAPP gene family members. AB - We report the high-resolution localization of the human calcitonin/CGRP genes, CALCA, CALCB, and the pseudogene CALCP, to a 220-kb SacII fragment on chromosome 11p15.2-p15.1, using prometaphase fluorescence in situ hybridization (FISH), two color interphase FISH, and pulsed-field gel electrophoresis analysis. The related islet amyloid polypeptide (IAPP) gene was assigned to human chromosome 12p12.3 p12.1. The results support an evolutionary relationship between the calcitonin/CGRP genes and the IAPP gene and between parts of human chromosomes 11 and 12. PMID- 8468048 TI - Molecular cloning of the b subunit of mouse coagulation factor XIII and assignment of the gene to chromosome 1: close evolutionary relationship to complement factor H. AB - The b subunit of human coagulation factor XIII (FXIII-b) is composed of 10 short consensus repeats (SCRs) characteristic of the regulatory proteins of complement activation system. A full-length cDNA clone of mouse FXIII-b was isolated and the entire sequence was determined. The predicted amino acid sequence showed 77.5% homology with human FXIII-b, although mouse FXIII-b contained seven extra amino acid residues at the carboxyl terminal. The strong reactivity of the translation product of this clone with rabbit anti-human FXIII-b antiserum confirmed that it encodes a mouse counterpart of the human FXIII-b. By in situ hybridization and mapping studies using 66 interspecific backcross mice, the mouse FXIII-b gene (designated F13b) was shown to be located on distal chromosome 1 closely linked to Cfh, extending a conserved linkage group between human and mouse chromosome 1. In addition, a significant structural similarity between FXIII-b and complement factor H is described. PMID- 8468049 TI - Molecular dissection of an extrachromosomal amplicon reveals a circular structure consisting of an imperfect inverted duplication. AB - A mouse fibroblast line, B-1/50, with a 4300-fold amplification of the adenosine deaminase gene locus (Yeung et al., 1983, J. Biol. Chem. 258: 8338-8345), was shown by in situ hybridization to harbor the amplified sequences on variously sized extrachromosomal elements. We show here that the smallest circle is approximately 500 kb. We describe a facile screening technique for identifying cosmid and yeast artificial chromosome (YAC) clones derived from the amplicon. A closed molecular map was generated by arranging the cosmids and YACs into a contig spanning over 250 kb of the adenosine deaminase gene locus. YACs from the two ends of this contig were shown to delimit a 250-kb inverted duplication. Long range mapping of a SalI partial digest of B-1/50 DNA is also consistent with the interpretation that the 500-kb adenosine deaminase amplicon in B-1/50 cells is an inverted duplication. The finding that this amplicon is the only or predominant structure containing amplified sequences in the B-1/50 cell line suggests that such structures are not inherently prone to high frequency rearrangement, even when present at such high copy number. This study provides the first molecular description of the structure of an episome involved in mammalian gene amplification. The implications of this finding for models of gene amplification and episome formation are discussed. PMID- 8468050 TI - Physical mapping and YAC contig analysis of the region surrounding Xist on the mouse X chromosome. AB - The Xist sequence has been proposed as a potential candidate for the X inactivation center based both on its localization within the candidate region for the X-inactivation center in man and mouse and on its unique pattern of expression from the inactive X chromosome. We have cloned 550 kb of DNA surrounding the mouse Xist sequence in contiguously overlapping YAC clones and have developed a long-range restriction map that spans almost 1 Mb of this region and includes this YAC contig. The detailed restriction map we have established provides a framework for the identification of expressed sequences other than Xist that may equally exhibit unusual expression characteristics associated with X inactivation. The presence of possible structural or methylation differences within this region between the active and inactive X chromosomes has been investigated through comparative analysis of male and female genomic DNA, and we report here the identification of certain CpG-containing restriction sites around Xist that have an interesting differential methylation status on the inactive and active X chromosomes. PMID- 8468051 TI - Physical mapping of 2000 kb of the mouse X chromosome in the vicinity of the Xist locus. AB - A physical map encompassing approximately 2.0 megabases (Mb) in the region of the mouse X-inactivation center has been constructed. The map extends from the Gjb-1 locus to the Xist locus and demonstrates the order of probes inseparable by genetic analysis. The deduced locus order is as follows: Gjb-1, Ccg-1, DXCrc171, Rps4, Phka, DXCrc177, DXCrc318, Xist. Detailed physical mapping in the region between the Phka and Xist loci indicates the position of CpG-rich islands associated with the 5' end of genes. The DXCrc177 and DXCrc318 loci, both defined by probes derived from linking clones, are associated with CpG-rich islands. The map provides a framework for the isolation of underlying sequences in the mouse X inactivation center region. PMID- 8468052 TI - A 37-kb fragment common to the pericentromeric region of human chromosomes 13 and 21 and to the ancestral inactive centromere of chromosome 2. AB - A YAC clone from a chromosome 21-specific partial library was localized by in situ hybridization to the pericentromeric region of chromosomes 13 and 21 and to the long arm of chromosome 2, where an ancestral inactive centromere is present. Restriction mapping of the insert showed that it may contain tandemly repeated DNA. Probes for alpha-satellite and satellite II and III failed to hybridize with the cloned DNA. Shotgun subcloning might reveal a sequence that seems to be specific for chromosome 21. Alu-PCR was performed to generate probes from the YAC clone to map it more precisely, using a somatic hybrid containing only human chromosome 21. The inter-Alu sequences thus isolated were found to be clustered in an approximately 37-kb-long fragment common to chromosome 2, 13, and 21, which might be involved in the centromeric function of these chromosomes. PMID- 8468053 TI - Structural organization of the human isovaleryl-CoA dehydrogenase gene. AB - Isovaleryl-CoA dehydrogenase (IVD) catalyzes the third step in leucine catabolism. The genetic deficiency of IVD causes isovaleric acidemia. The functional IVD gene spans approximately 15 kb and consists of 12 exons and 11 introns, with the exon size ranging from 52 to 728 bp. The poly(A) addition site begins 21 nucleotides downstream of this signal. The 5'-flanking region contained typical promoter elements such as TATA and CAT boxes in addition to other putative regulatory sequences. The transcription start site appeared to be located 344 bp upstream of the initiator methionine codon. The GC content in this region is very high. In Northern blot analysis, the IVD cDNA probe hybridized to three RNA species of sizes 2.1, 3.6, and 4.8 kb, respectively. The 2.1-kb band corresponds to the size of IVD cDNA. The results from experiments using an IVD specific oligomer and stringent washes with 3.0 M tetramethylammonium chloride suggested that high GC content may have caused hybridization of the probe to the 3.6- and 4.8-kb species. PMID- 8468054 TI - Isolation and characterization of a human pseudogene for the regulatory subunit RI alpha of cAMP-dependent protein kinases and its sublocalization on chromosome 1. AB - Using a human cDNA (complementary DNA) encoding the regulatory subunit RI alpha of cAMP-dependent protein kinases (PKA) as a probe, a pseudogene for this PKA isoform was isolated from a human genomic library. The human RI alpha pseudogene was 89% similar to the open reading frame of the expressed human RI alpha at the nucleotide level. Several stop codons were found, indicating that the pseudogene does not encode a functional protein. The pseudogene also contained several frameshift mutations, small deletions, and insertions. No introns were found in the region corresponding to the open reading frame of the expressed RI alpha cDNA. Specific oligonucleotides for the RI alpha gene and pseudogene were constructed and used as primers in polymerase chain reaction (PCR) to amplify human DNA from healthy blood donors. Probing of the PCR products using oligonucleotides specific for the RI alpha gene and RI alpha pseudogene, respectively, showed the presence of both genes in the human genome. When DNA extracted from various somatic cell hybrids was amplified, it was shown that the RI alpha gene was located on human chromosome 17, whereas the RI alpha pseudogene was located in the p21-p31 region on chromosome 1. This is the first report describing a pseudogene for a subunit of cAMP-dependent protein kinases from any species. PMID- 8468055 TI - Isolation and characterization of the mouse thrombospondin 3 (Thbs3) gene. AB - The DNA sequence of the coding region of the mouse thrombospondin (TSP) 3 gene has been determined by analysis of both genomic and cDNA clones. Like TSP1 and TSP2, TSP3 has a homologous COOH-terminal domain and seven type III (Ca(2+) binding) repeats. However, TSP3 contains four, rather than three, type II repeats and lacks the type I (TSP or properdin) repeats and procollagen homology characteristic of TSP1 and TSP2. In addition, the NH2-terminal domain of TSP3 differs markedly, both in sequence and in exon/intron structure, from that in TSP1 or TSP2. The gene is located on mouse chromosome 3, bands E3-F1, immediately upstream from the Muc1 (episialin) gene and is expressed in the developing mouse in a pattern that also differs from that of TSP1 or TSP2. Based on its structure, we suggest that TSP3 may play both a unique role in cell-matrix interactions and perform functions that overlap with those of TSP1 and TSP2. PMID- 8468056 TI - The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression. AB - Genes encoding T-cell-receptor alpha/delta chains, neutrophil cathepsin G, and lymphocyte CGL/granzymes are closely linked on chromosomal band 14q11.2. The current work identifies the human mast cell chymase gene (CMA1) as the fourth protease in this cluster and maps the gene to within 150 kb of the cathepsin G gene. The gene order is centromere-T cell receptor alpha/delta-CGL-1/granzyme B CGL-2/granzyme H-cathepsin G-chymase. Chymase and cathepsin G genes are shown to be cotranscribed in the human mast cell line HMC-1 and in U-937 cells. Other cells transcribe cathepsin G or CGL/granzyme genes, but not chymase genes, suggesting a capacity for independent regulation. Comparison of the 5' flank of the chymase gene with those of cathepsin G and CGL/granzymes reveals little overall homology. Only short regions of the 5' flanks of the human and murine chymase gene sequenced to date are similar, suggesting that they are more distantly related than human and rodent CGL-1/granzyme B, the flanks of which are highly homologous. The expression patterns and clustering of genes provide possible clues to the presence of locus control regions that orchestrate lineage restricted expression of leukocyte and mast cell proteases. PMID- 8468057 TI - A novel zinc finger cDNA with a polymorphic pentanucleotide repeat (ATTTT)n maps on human chromosome 19p. AB - To isolate genes that contain zinc finger motifs, a human brain cDNA library was screened with an oligonucleotide complementary to the conserved "linker" sequence between adjacent zinc fingers. The insert of one positive clone of 1226 nucleotides contained a novel open reading frame (ZNF121) with 9 zinc finger motifs; in addition, 10 repeats of the pentanucleotide sequence (ATTTT) were found 223 nucleotides after a stop codon and were followed by an Alu repeat. A sequence-tagged site of 172 nucleotides containing this repeat was defined by two oligonucleotide primers, mapped to chromosome 19 using commercially available mapping panels of hybrid cell lines, and designated D19S204. The pentanucleotide repeat was polymorphic in the members of CEPH families, with 7 alleles ranging in size from 147 to 197 nucleotides. The observed heterozygosity in unrelated CEPH parents was 58% (46 of 79). Genotypes from 34 informative CEPH families were used to perform linkage analyses with other polymorphic markers contained in the CEPH V5 database; strong linkage was found with markers on the short arm of chromosome 19. The zinc finger cDNA described here maps in an area where other zinc finger sequences and multiple cosmid clones containing zinc fingers have been previously localized. The ease of scoring these polymorphic alleles indicates that pentanucleotide repeat polymorphisms may be a particularly useful class of DNA markers for linkage studies. PMID- 8468058 TI - A contiguous physical map of the pericentromeric region of chromosome 21q between D21Z1 and D21S13E. AB - We constructed a long range restriction map of the pericentromeric 21q region between the centromere, identified by the alphoid DNA sequence D21Z1, and D21S13E. The physical map showed the order and intermarker distances of five new loci, including two for which highly informative dinucleotide repeat polymorphisms were identified. The total distance between D21Z1 and D21S13E was 2400 kb. Comparison of genetic and physical distances indicated that there is about 400 to 500 kb per centimorgan that is not significantly different from the average 470 kb per centimorgan for the whole of chromosome 21q. Our physical mapping results do not indicate suppression of recombination in pericentromeric 21q. PMID- 8468059 TI - Characterization of the apolipoprotein AI and CIII genes in the domestic pig. AB - The apolipoproteins (apo) AI and CIII are important constituents of triglyceride rich lipoproteins and high-density lipoproteins. In humans, apo AI is believed to play an important protective role in the pathogenesis of arteriosclerosis, whereas apo CIII might be involved in the development of hypertriglyceridemia. Both human genes are located within a gene cluster on chromosome 11. Although the domestic pig has been widely used as an animal model in arteriosclerosis and lipid research, the porcine apolipoproteins genes are poorly characterized. In this report, the complete nucleotide sequences of the porcine apo AI and CIII genes are presented and we demonstrate, for the first time, apo CIII expression in the pig. Both genes are composed of four exons and three introns and resemble closely their human counterparts with regard to the transcriptional start sites, exon sizes, intron sizes, exon-intron borders, and the size of the intergenic region. The predicted pig apo AI is a protein of 241 amino acids, which is 2 amino acids shorter than human apo AI. The protein sequence was found to be very homologous to apo AI sequences in other mammalian species. Apo AI expression was detected on the mRNA level in porcine liver and intestine. The apo CIII gene encodes a protein with 73 amino acids, which is 6 amino acids shorter than human apo CIII. In contrast to the three isoforms of apo CIII found in humans, only one major isoform was detected in the pig. Presumably this isoform is unglycosylated. In addition to apo CIII expression in the liver and the intestine, a truncated form of apo CIII mRNA was also found in porcine kidney. Our studies demonstrate the presence of an apo CIII gene, an apo CIII mRNA, and an apo CIII protein in the pig and, therefore, exclude a hypothesized apo CIII deficiency in these animals. PMID- 8468060 TI - A human chromosome 11 NotI end clone library. AB - A NotI end clone library has been constructed from a human-hamster hybrid cell line containing only human chromosome 11. Fifty-one NotI clones were chosen to characterize the library. The majority of NotI clones hybridize to small 15- to 200-kb fragments and have proven to be valuable for chromosome 11 physical mapping by detecting fragments not previously recognized by random probes. These NotI end clones have been used to isolate corresponding NotI linking cosmids which were then used to identify adjacent NotI fragments on pulsed-field gels. The clones were mapped using fluorescence in situ hybridization and a somatic cell hybrid panel. Although these clones were localized over the entirety of chromosome 11, a nonrandom distribution was observed. Northern blot analysis indicated that 57% (17/30) of the NotI clones examined detected poly(A)+ transcripts in HeLa cell RNA. PMID- 8468061 TI - An experimentally derived data set constructed for testing large-scale DNA sequence assembly algorithms. AB - A data set consisting of DNA sequences from a large-scale shotgun DNA cloning and sequencing project has been collected and posted for public release. The purpose is to propose a standard genomic DNA sequencing data set by which various algorithms and implementations can be tested. This set of data is divided into two subsets, one containing raw DNA sequence data (1023 clones) and the other consisting of the corresponding partially refined or edited DNA sequence data (820 clones). Suggested criteria or guidelines for this data refinement are presented so that algorithms for preprocessing and screening raw sequences may be developed. Development of such preprocessing, screening, aligning, and assembling algorithms will expedite large-scale DNA sequencing projects so that the complete unambiguous consensus DNA sequences will be made available to the general research community in a quicker manner. Smaller scale routine DNA sequencing projects will also be greatly aided by such computational efforts. PMID- 8468062 TI - Reassignment of the human ARH9 RAS-related gene to chromosome 1p13-p21. AB - The human ARH9 gene (originally rhoC), a member of the RAS gene superfamily, was initially isolated on the basis of cross-hybridization with a RAS-related cDNA from the marine snail Aplysia. The ARH9 gene locus was previously assigned to the telomeric region of chromosome 5q by isotopic chromosomal in situ hybridization and Southern analysis of somatic cell hybrid DNAs; the gene was noted to cosegregate with the CSF1 gene locus in human-rodent somatic cell hybrids carrying partial chromosomes 5, together with other human chromosomes. With the recent reassignment of the human CSF1 locus to chromosome 1, region p13-p21, it seemed important to reexamine the localization of the ARH9 gene, since it segregates 100% concordantly with the CSF1 locus in hybrid cells. Results of our investigation demonstrate that the ARH9 locus is also present in hybrids retaining chromosome 1, but not 5. Using hybrids carrying partial 1p, we mapped the ARH9 locus relative to other 1p loci, localizing the gene to the region 1p13 p31. Fluorescence in situ hybridization to metaphase chromosomes with a genomic ARH9 clone refined the gene's localization to chromosome 1, bands p13-p21. PMID- 8468063 TI - A set of STS assays targeting the chromosome 22 physical framework markers. AB - The widespread use of the sequence-tagged site (STS) as a quick, efficient, and reproducible assay for comparing physical and genetic map information promises to facilitate greatly long-range goals of the mapping of the human genome. We have designed 21 STS assays for loci on human chromosome 22. These assays primarily tag the physical framework markers of the long arm of 22, but additional assays have been designed from known genes and loci in the neurofibromatosis 2 (NF2) region. The availability of these assays will make these loci available to the research community without physical transfer of materials and will serve as start points for further efforts to physically map chromosome 22 with yeast artificial chromosome clones. PMID- 8468064 TI - Assignment of the cysteinyl-tRNA synthetase gene (CARS) to 11p15.5. PMID- 8468065 TI - The human cell cycle gene CDC25B is located at 20p13. PMID- 8468066 TI - Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids. PMID- 8468067 TI - Assignment of the human glutamate receptor gene GLUR5 to 21q22 by screening a chromosome 21 YAC library. PMID- 8468068 TI - Correction for apparent prolongation of mean transit time resulting from response time in a thermodilution system. AB - We investigated a method of correcting an apparent prolongation in the measured mean transit time (MTT), resulting from the response time of the thermodilution system. We measured the mean response times (MRT) for five commercially available thermistor-tipped catheters by recording their step function response curves. MRT is the sum of the time from the point of step change to the point of the first detection of change in temperature (latency time) plus the time from the first detection to the point of 63.2% of full response (time constant). By using a flow loop model filled with saline through a mixing chamber, we recorded pairs of thermodilution curves simultaneously with pairs of catheters, and studied the influence of MRT on MTT over the constant flow rates of 1-6 L/min. The difference in MRT's (delta MRT, second) between a pair of thermodilution systems correlated with the difference in MTT's (delta MTT, second) between a corresponding pair of thermodilution curves, yielding an equation: delta MTT = 1.07 delta MRT = 0.04 (n = 72, r = 0.95), delta MTT/delta MRT = 1.02 +/- 0.18 (mean +/- SD). We conclude that an apparent prolongation of MTT due to response time is removable by subtracting MRT from measured MTT. PMID- 8468069 TI - Temperature dependence of reflectance and transmittance of the artery exposed to air during laser irradiation. AB - Reflectance, transmittance, and temperature of the arterial wall exposed to air are measured during laser irradiation for different heating dynamics. Temperature dependence of the reflectance and transmittance is then deduced. Our results show a competing effect between temperature and dehydration, resulting in a distinct minimum of transmittance and maximum of reflectance. As a consequence, a direct correlation of reflectance and transmittance with temperature is only possible for a specific dynamics. PMID- 8468070 TI - Analytical study of temperature oscillations in living tissues. AB - A nonlinear, time-delay differential equation is postulated as a possible structure to describe the temperature dynamics at a point inside living tissue. The presented analysis explains how this differential equation can lead to four different temperature response types that have been previously observed in vivo. PMID- 8468071 TI - An RF concentrating method using inductive aperture-type applicators. AB - A method for concentrating em energy of a low frequency in hyperthermia is proposed. The phantom together with boli are placed between a pair of inductive aperture-type applicators. The calculated results show that the method can heat the deep portion of the phantom without overheating the fat layers excessively. PMID- 8468072 TI - Accelerometer type cardiac transducer for detection of low-level heart sounds. AB - New applications in phonocardiography require transducers with high sensitivity, low noise, and extended frequency range. This paper compares several different cardiac transducers and describes the development of a low-mass, accelerometer type cardiac transducer which fulfills these objectives. The accelerometer weighs approximately 5 g and has a theoretical sensitivity of 125 mV/g in the frequency range 200-800 Hz. The basic design allows for easy modification of sensitivity and resonant frequency. This transducer has been effective in detecting sounds associated with turbulent blood flow in partially occluded coronary arteries. PMID- 8468073 TI - Using compound electrodes in electrical impedance tomography. AB - In electrical impedance tomography, we inject currents and measure voltages to estimate an object's resistivity distribution. The electrode configuration affects measured voltage data because the electrode-skin contact impedance is high and varies with electrode location. We developed a compound electrode which is composed of two electrodes: a large outer electrode to inject current and a small inner electrode to sense voltage. We used these compound electrodes to measure voltages from a physical phantom. We showed that the measured voltages from the compound electrodes are smaller in amplitude than those from conventional electrodes. This demonstrates that the compound electrode can minimize contact impedance voltage drop from the measured data. We used a finite element model for the compound electrode and incorporated the model into the regularized Newton-Raphson reconstruction algorithm. We performed a sensitivity study and showed that the reconstructed resistivity distributions are less dependent on the unknown contact resistance values for a compound electrode than a conventional electrode and that the use of a compound electrode results in improved images for the reconstruction algorithm. PMID- 8468074 TI - Modeling the neuron-microtransducer junction: from extracellular to patch recording. AB - This paper is devoted to a detailed characterization of the neuron-to microtransducer junction, based on the equivalent electric-circuit approach. As a result, recording of action potentials can be simulated with the general-purpose network-analysis program SPICE. Both noble-metal microelectrodes and insulated gate FET's are considered. The responses of such devices are characterized as functions of several parameters, e.g., sealing impedance, density of ionic currents in the cell membrane, and spatial discontinuities of the adhesion process. It is shown that the various signal shapes reported in the literature can be reproduced and interpreted in terms of time derivatives of the action potential. In this way, the shape of any experimental signal can be interpreted on the basis of a specific sealing condition. Possible future improvements in microtransducer design, based on the proposed approach, are also suggested. PMID- 8468075 TI - Effects of local variations in skull and scalp thickness on EEG's and MEG's. AB - Many studies have been performed on the effects of various features of head geometry on electroencephalograms (EEG's) and magnetoencephalograms (MEG's) and on the accuracy with which electrical sources in the brain can be localized using these measurements. However, to date no studies have been performed of the effects of local variations in skull and scalp thickness. This paper presents a computer modeling study of the effects of such local variations. The results obtained in this study indicate that local variations in skull and scalp thickness have effects on EEG's and MEG's which range from a simple intuitive effect to complex effects which depend on such factors as source depth and orientation, the geometry of the variation in skull and scalp thickness, etc. These results also indicate that local variations in skull and scalp thickness cause EEG localization errors which are generally much less than 1 cm and MEG localization errors which are even smaller. These results also indicate that multichannel and single-channel MEG measurements will produce localization errors of approximately the same amplitude when there is a bump on the external surface of the head but that multichannel measurements will produce significantly smaller localization errors than single-channel measurements when a depression is present in that surface. PMID- 8468076 TI - A simulation of cardiac action currents having curl. AB - A digital simulation of a two dimensional cardiac slice has been performed. It is stimulated at the center and an action potential propagates outward. An anisotropic bidomain model is used in which fast sodium physiology connects the intracellular and extracellular domains. For cases in which the inner asymmetry (expressed as longitudinal versus transverse electrical conductivity) is greater than the outer asymmetry, a current flow pattern is observed for which there is nonzero curl. Such a result explains recent observations of nonzero Bz magnetic field detected above a slab of tissue in the x-y plane. The current loop producing this field consists of outer domain current in the longitudinal direction flowing around in space to return at the AP location in the transverse direction in the outer domain and then completing the loop in the longitudinal direction by passing distally through the AP in the inner domain where resistance is extremely low. PMID- 8468077 TI - Single-trial processing of event-related potentials using outlier information. AB - A new approach to extracting single-trial event-related information is described in this paper. This approach, called the outlier processing method (OPM), is based on the concept that event-related information is contained in EEG time series outliers. In particular, the OPM has been effective in extracting motor related information from single-trial EEG. An investigation into the viability of the OPM was carried out on single-trial EEG data from four subjects. The EEG was collected under two conditions: an active task in which the subject performed a skilled thumb movement and an idle task in which the subject remained alert but did not carry out any motor activity. The results of this investigation demonstrated that consistent single-trial motor related information can be successfully extracted using the OPM. PMID- 8468078 TI - A time domain approach for the fluctuation analysis of heart rate related to instantaneous lung volume. AB - This paper presents a time domain technique for estimating transfer characteristics from fluctuations of instantaneous lung volume (ILV) to heart rate (HR). An effective procedure for estimating the impulse response of HR to ILV is proposed. Pre- and post-processing procedures, including prefiltering of the HR signal, preenhancement of the high frequency content of the ILV signal, and post-filtering of the estimated impulse response, together with a random breathing technique, are shown to effectively reduce spurious transfer gain so as to get a stable estimate of the impulse response. Analysis of the data collected from fourteen healthy male subjects in various conditions revealed that there are three components in the impulse response: fast positive, delayed slow negative, and oscillatory. The effects of the autonomic blocking agents propranolol and atropine on these transfer characteristics are also described. PMID- 8468079 TI - On the efficacy of linear system analysis of renal autoregulation in rats. AB - In order to assess the linearity of the mechanisms subserving renal blood flow autoregulation, broad-band arterial pressure fluctuations at three different power levels were induced experimentally and the resulting renal blood flow responses were recorded. Linear system analysis methods were applied in both the time and frequency domain. In the frequency domain, spectral estimates employing FFT, autoregressive moving average (ARMA) and moving average (MA) methods were used; only the MA model showed two vascular control mechanisms active at 0.02 0.05 Hz and 0.1-0.18 Hz consistent with previous experimental findings [Holstein Rathlou et al., Amer. J. Physiol., vol. 258, 1990.]. In the time domain, impulse response functions obtained from the MA model indicated likewise the presence of these two vascular control mechanisms, but the ARMA model failed to show any vascular control mechanism at 0.02-0.05 Hz. The residuals (i.e., model prediction errors) of the MA model were smaller than the ARMA model for all levels of arterial pressure forcings. The observed low coherence values and the significant model residuals in the 0.02-0.05 Hz frequency range suggest that the tubuloglomerular feedback (TGF) active in this frequency range is a nonlinear vascular control mechanism. In addition, experimental results suggest that the operation of the TGF mechanism is more evident at low/moderate pressure fluctuations and becomes overwhelmed when the arterial pressure forcing is too high. PMID- 8468080 TI - A new strategy for multifunction myoelectric control. AB - This paper describes a novel approach to the control of a multifunction prosthesis based on the classification of myoelectric patterns. It is shown that the myoelectric signal exhibits a deterministic structure during the initial phase of a muscle contraction. Features are extracted from several time segments of the myoelectric signal to preserve pattern structure. These features are then classified using an artificial neural network. The control signals are derived from natural contraction patterns which can be produced reliably with little subject training. The new control scheme increases the number of functions which can be controlled by a single channel of myoelectric signal but does so in a way which does not increase the effort required by the amputee. Results are presented to support this approach. PMID- 8468081 TI - Seat support surface optimization using force feedback. AB - The development, implementation and evaluation of an algorithm designed to find optimal seat support surfaces is presented. The algorithm has been developed and implemented on an active contour measurement device. The device consists of an array of positioning elements equipped with force sensors for feedback. With a patient seated on the array, the algorithm is designed to find a seat contour that optimally satisfies given performance criteria. The performance criteria are based on measured stiffness of the soft tissues. A theoretical development of the algorithm is presented along with the modifications made to the algorithm during implementation. The results from several tests using man-made test bodies and a prototype contour gage are presented to verify the algorithm's performance. PMID- 8468082 TI - The regenerative potential of plaque-induced peri-implant bone defects treated by a submerged membrane technique: an experimental study. AB - The aim of the present study was to experimentally induce peri-implant bone defects around three different types of implants by plaque accumulation and to determine whether new bone formation can occur on previously contaminated dental implants. Dental implants were placed into the mandibles of beagle dogs. Gross plaque accumulation around the implants was undisturbed for 3 months, which resulted in circumferential peri-implant bone defects. Bony defects surrounding the hydroxyapatite implants were significantly greater than those around the titanium implants. Surgical treatment consisted of granulation tissue removal, preparation of the implant surface, and the placement of an e-PTFE membrane over each test implant. Before the flap was closed to cover the implants, perforations were made into the cancellous bone. Each control implant received identical treatment, but without placement of a membrane. Surgical exposure after an uneventful submerged healing period showed evidence of closure of the peri implant bone defects. Corresponding histologic examination of 2-month sections demonstrated large amounts of rapidly formed lamellar bone beneath the membrane. Some areas of the previously contaminated implant surface showed evidence of "re osseointegration." These preliminary results support the hypothesis that plaque induced peri-implant bone defects can be successfully treated by a submerged membrane technique in the dog model. PMID- 8468083 TI - The biomechanics of force distribution in implant-supported prostheses. AB - Force distribution with natural teeth depends on micromovement induced by the periodontal ligament. The location and cusp inclination of the tooth qualitatively alter the force pattern. Osseointegrated implants do not have micromovement associated with force distribution. Force distribution to the osseointegrated implant interface is completely different than with natural teeth. Alterations in tooth location and cusp inclination are suggested to limit implant overload. Force distribution in splinted natural teeth and osseointegrated prostheses are compared. The mechanism of interface force distribution and the consequences of poor interface fit are interrelated. The differential mobility of splinted natural teeth affects diagnosis and treatment. However, combining natural teeth with an osseointegrated prosthesis requires new design principles. PMID- 8468084 TI - Surface analysis of four dental implant systems. AB - Dental implants obtained from four suppliers were analyzed by electron spectroscopy for chemical analysis and scanning electron microscopy. Three of the implants were delivered in a sterilized condition, while the fourth implant was delivered in a plasma-sprayed condition. The covering oxide layer consisted mainly of TiO2. Divalent and trivalent states of titanium were also detected, showing that TiO and Ti2O3 layers occurred. The thickness of the oxide formed on the plasma-sprayed implant was 3.4 nm. The oxide thicknesses of the sterilized implants were 4.6 +/- 0.4 nm. The surfaces of all samples were covered with organic contaminants. A strong fluorine signal was obtained from one sample, indicating that the supplier etches the implants in hydrofluoric acid. Calcium and zinc were found on the surfaces of all samples from one supplier, while calcium and silicon were found on the surfaces of the implants from another supplier. It is suggested that inorganic contaminants should be avoided because these species can possibly provoke the dissolution of titanium. PMID- 8468085 TI - Effect of hyperbaric oxygen therapy on osseointegration of titanium implants in irradiated bone: a preliminary report. AB - Four patients who had undergone combined surgical and radiotherapeutic treatment for maxillofacial cancer had osseointegrated titanium implants placed in the bone of the treated region at various intervals after irradiation. Preoperatively and postoperatively, hyperbaric oxygen therapy was administered to the patients at the level of 2 or 3 atmosphere absolute (ATA). Of the 21 fixtures placed, one was lost because of lack of osseointegration, rendering the survival rate 92.3%. Hyperbaric oxygen therapy seemed to be a viable method to improve the survival rate of fixtures in irradiated bone tissue. PMID- 8468086 TI - Bone grafts and Branemark implants in the treatment of the severely resorbed maxilla: a 2-year longitudinal study. AB - A combination of horseshoe-shaped iliac bone grafts and Branemark implants was used in 30 patients with severely resorbed maxillary alveolar ridges. All patients were followed clinically for 2 years and evaluated with regard to prosthesis stability, fixture survival, wound healing complications, and soft tissue conditions. Surgery was performed by the same oral surgeons using identical procedures, and the prosthetic treatment was performed by the same prosthodontist. The development group included the first 10 patients and the routine group included the following 20. Fixture survival in the development group was 54.4%, whereas 88.3% of the fixtures in the routine group have survived after 2 years. The average fixture survival in the study was 77.4%. Three patients in the development group lost all fixtures, primarily the result of trauma to the grafted region. With respect to the difficult situation many of these patients experienced, the survival rate should be considered most acceptable. PMID- 8468087 TI - Implant-supported fixed prosthesis treatment of a patient with Sjogren's syndrome: a clinical report. AB - Many completely and partially edentulous patients experience advanced xerostomia and have considerable difficulty wearing tissue-supported prostheses. A conservative, maximum bone preservation approach to immediate implant placement is presented. The surgical and prosthetic considerations for treating a patient with Sjogren's syndrome are reviewed and discussed. PMID- 8468088 TI - Effects of drill cooling and bone structure on IMZ implant fixation. AB - Alternating use of the original method of internal drill cooling with manual external cooling, one IMZ implant was placed in the diaphysis (compact bone) and metaphysis (spongy bone) of the left distal tibia in each of six sheep. After polyfluorochrome sequential labeling, two animals survived for 4, 8, and 16 weeks without functional loading of the implants. The drill holes and bone-implant reactions were evaluated in undecalcified ground sections and microradiographs, using computer-aided histomorphometry. At least 30% of all drill holes were incongruent, but up to 25% of the implant surfaces had primary bone contacts. Four weeks after implantation, distinct differences in the bone reactions could be determined between the experimental conditions. After both cooling methods, osteoclastic resorption had extended up to 0.5 mm into peri-implant compact bone and up to 0.18 mm into spongy bone. Based on the percentage of newly formed bone to-implant contacts, external cooling proved superior at all superficial drill hole levels in compact bone and in all spongy bone beds, while internal cooling was only better at the deeper drill hole levels in compact bone. After 8 and 16 weeks, peri-implant bone remodeling led to further increased new bone-implant contacts, irrespective of incongruent drill holes or cooling methods. At all time periods, abraded titanium particles were observed within interfacial foreign body cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468089 TI - Failures in the osseointegration of endosseous implants. AB - A total of 68 patients, 26 men and 42 women, aged 21 to 86 years, were treated with 204 endosseous implants (TPS, ITI, Bonefit, or Biolox) from 1985 to 1990. They were examined at their latest recall visit approximately 22.5 months after surgery, the range varying greatly between the implant systems used (from 4 to 60 months). Fourteen implants were lost during the observation period because of failures in osseointegration. There were no statistically significant differences in success rates between the implant systems during the observation period. The Periotest values, however, differed between the Bonefit and ITI implants in maxillae (P < .001) and mandibles (P < .01), and between successful and failed TPS implants (P < .001, unpaired t test). In four of the failures, all ITI implants, the prosthetic restorations (fixed dentures and single crowns) had been lost. All other failures were treated by using the previous complete denture. Possible causes of failure included advanced age and poor general health of the patient, complications in the surgical procedures, and compromised oral hygiene. PMID- 8468090 TI - Prosthodontic restoration with dental implants and an intraoral cranial bone onlay graft: a case report. AB - In 1988, a 54-year-old edentulous patient received a cranial bone onlay graft with the immediate placement of five dental implants. Treatment procedures and early results of restoration are described. PMID- 8468091 TI - Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. AB - The following are the conclusions that can be derived from a review of the literature regarding the role of infection in the aetiology of male infertility. (i) Temporary inflammatory episodes in the male reproductive tract which are self limiting are probably common. (ii) Caution should be exercised in the use of leukospermia or bacteriospermia as parameters for glandular infection. (iii) There is a need for alternative techniques for detecting non-symptomatic deep pelvic infections in the male; one technique of great promise is rectal ultrasound. (iv) Rectal ultrasound indicates that a large number of men with poor sperm quality have a non-symptomatic, chronic prostatovesiculitis. (v) Increasing evidence implicates Chlamydia trachomatis as being a major cause of chronic non bacterial prostatitis. (vi) An important aspect of chlamydial infections in men may be that the male accessory sex glands may function as reservoirs for the organism, increasing the probability of infection in the female. (vii) Ureaplasma urealyticum may also play an important aetiological role in male infertility but its significance is confounded by its acknowledged function as a commensal in the reproductive tract. (viii) One of the manifestations of male reproductive tract infection is the induction of sperm autoantibodies. (ix) There is a need for more systematic controlled studies of the effects of antibiotic treatment on sperm quality with different preparations for extended periods using patient groups in which a glandular infection has been verified, e.g. by rectal ultrasonography. PMID- 8468092 TI - The influence of sperm density on the motility characteristics of washed human spermatozoa. AB - To study the effects of sperm density on the results of computer-assisted semen analysis (CASA), 10 washed semen samples were diluted and measured with the CellTrak/S CASA system in a concentration range of 10-180 x 10(6) spermatozoa/ml. All sperm motility parameters were influenced to some extent by sperm density. The motility percentage was influenced significantly in 5 samples (P < 0.005), the straight line velocity in all samples (P < 0.0005 in 7 samples), the curvilinear velocity in 3 samples (P < 0.005), the linearity in 9 samples (P < 0.0005 in 6 samples) and the lateral head displacement in 9 samples (P < 0.005 in 6 samples). In general, the CellTrak/S data are influenced significantly if sperm density exceeds 50 x 10(6) spermatozoa/ml. The influence of sperm density on the motility parameters can be explained both by the accuracy of the CASA system and by actual changes in the motility of the spermatozoa. In the light of other published studies, it is concluded that sperm motility measurements with CASA systems should be assessed using 25-50 x 10(6) spermatozoa/ml, especially in studies concerning lateral head displacement and the linearity, as in sperm hyperactivation studies. PMID- 8468093 TI - Enhancement of testosterone secretion by normal adult human Leydig cells by co culture with enriched preparations of normal adult human Sertoli cells. AB - An in-vitro method was developed to study Sertoli-Leydig cell interactions in man, using testes removed at the time kidneys were removed for transplantation from 6 young adult men (aged 17-45 years) after cerebral death. After collagenase digestion of testicular tissue, Leydig cells were purified on discontinuous Percoll gradients. Two fractions of Leydig cells, 'L2' and 'L3' which differed in their buoyant density (1.05 g < L2 < 1.06 g and 1.06 g < L3 < 1.08 g), were obtained. The Sertoli cell-enriched preparation was obtained from seminiferous tubular fragments after sequential treatment with glycine buffer to remove peritubular-myoid cells, a second collagenase digestion, mechanical fragmentation and washes to remove germ cells. Purified Leydig cells were then cultured either alone or together with Sertoli cells in culture dishes coated with collagen, fibronectin and laminin in a chemically defined medium without serum. The influence of co-culture on basal testosterone secretion was examined in 3 successive 48 h periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468094 TI - Contents of fructose, citric acid, acid phosphatase, proteins and electrolytes in secretions of the accessory sex glands of the male golden hamster. AB - Secretions were collected from the ampullary gland, dorsolateral prostate, ventral prostate, coagulating glands and seminal vesicles of male golden hamsters aged 15-20 weeks. The concentrations of total protein, citric acid, fructose, acid phosphatase, chloride, sodium, potassium, calcium, magnesium and zinc were determined. The ampullary gland secreted predominantly citric acid, sodium and acid phosphatase. Zinc was secreted only by the prostatic complex, with the largest quantity coming from the coagulating gland. The highest concentrations of potassium, calcium and magnesium were found in secretions of the ventral prostate. The coagulating gland and dorsolateral prostate were the principal contributors to total protein. The hamster appears to be more related to the mouse than to the rat in terms of the secretory functions of its accessory sex glands. PMID- 8468095 TI - Immuno-competent cells in the murine epididymis following infection with Escherichia coli. AB - Epididymitis was induced by retrograde injection of Escherichia coli into the vas deferens of 28 mice. A group of 28 saline-injected animals served as controls. On Days 1, 3, 7 and 28, groups of seven animals were killed. Bacterial culture was performed. Leucocyte numbers and distribution were determined in epididymides. In infected mice, E. coli were isolated from all epididymides on Days 1 and 3, but only from five of seven epididymides on Days 7 and 28. One week after infection, the total number of macrophages rose from about 10 to 28%. Significantly increased macrophage percentages were also found in animals killed 28 days after infection. A simultaneous increase in MHC class II positive cells was seen on Day 7. A total of 20% of the cells expressed MHC class II in infected epididymides (normal = 6%). A similar increase was found on Day 28 after infection. Most of the macrophages and MHC class II positive cells were located in the interstitium, fewer in the peritubular layer and nearly none in the epithelium. The main increase in these cells occurred in the interstitium and, to a lesser but significant extent, in the peritubular area. T-helper and T-suppressor/cytotoxic lymphocytes reached peak values on Day 28. The increase in T-lymphocytes and simultaneous appearance of plasma cells followed the increase in numbers of macrophages and MHC class II positive cells. They were located mainly in the interstitium. A sequential increase in leucocyte subsets and negative culture results for E. coli were observed on Days 7 and 28 (2/7 on each day). The inflammatory process was restricted to the interstitium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468096 TI - Effects of high altitudes on finger cooling test in Japanese and Tibetans at Qinghai Plateau. AB - The influences of both hypobaric hypoxia and cold on peripheral circulation were studied using the finger cooling test (measurement of the decrease in finger temperature, measured at the dorsal surface of the finger, during immersion of the hand in 0 degrees C water for 20 min) at Qinghai Plateau. The same test was carried out at simulated altitudes in a 25 degrees C climatic chamber to separate the hypobaric hypoxia influence from that of cold. In Japanese subjects at Qinghai Plateau there was a significant difference between finger skin temperatures (FSTs) during 20 min of 0 degrees C water immersion at altitudes of 2260 m and 4860 m by ANOVA. Mean finger skin temperature during the 20-min immersion (5-20 min, MST) measured at 4860 m was significantly lower than that at 2260 m. In Tibetan subjects, there was also a significant difference between FSTs at 2260 m and at 4860 m by ANOVA. MST at 4860 m tended to be lower than that at 2260 m. In the 25 degrees C climatic chamber, there was a significant difference between FSTs of Japanese expedition members at 2000 m and at 4000 m by ANOVA. MST was higher at 4000 m than at 2000 m, contrary to the data obtained in Qinghai. In conclusion, the higher skin temperature in response to local cold immersion, which would have been caused by stronger hypobaric hypoxia, must have been masked by the lower ambient temperature. PMID- 8468097 TI - Respiratory changes due to extreme cold in the Arctic environment. AB - Effects of acute exposure and acclimatisation to cold stress on respiratory functions were investigated in healthy tropical Indian men (n = 10). Initial baseline recordings were carried out at Delhi and thereafter serially thrice at the arctic region and once on return to Delhi. For comparison the respiratory functions were also evaluated on Russian migrants (RM; n = 7) and Russian natives (RN; n = 6). The respiratory functions were evaluated using standard methodology on a Vitalograph: In Indians, there was an initial decrease in lung vital capacity (VC), forced vital capacity (FVC), forced expiratory volume 1st s (FEV1), peak expiratory flow rate (PEFR) and maximum voluntary ventilation (MVV) on acute exposure to cold stress, followed by gradual recovery during acclimatisation for 4 weeks and a further significant improvement after 9 weeks of stay at the arctic region. On return to India all the parameters reached near baseline values except for MVV which remained slightly elevated. RM and RN showed similar respiratory functions at the beginning of acute cold exposure at the arctic zone. RN showed an improvement after 10 weeks of stay whereas RM did not show much change. The respiratory responses during acute cold exposure are similar to those of initial altitude responses. PMID- 8468098 TI - Seasonal adaptation of thermal and metabolic responses in men wearing different clothing at 10 degrees C. AB - Thermoregulatory responses at ambient temperatures of 20 and 10 degrees C in six male subjects wearing two different kinds of clothing were compared between summer and winter. The two different kinds of clothing were one insulating the upper half of the body lightly and the lower half of the body heavily (clothing A, the weight in the upper and lower halves of the body being, respectively, 489 g and 1278 g) and the other insulating the upper half of the body heavily and the lower half of the body lightly (clothing B: 1212 g and 559 g). The major findings are summarized as follow. (i) Rectal temperature was kept significantly higher in clothing B than in clothing A both in summer and winter. (ii) The fall of rectal temperature was significantly greater in summer than in winter in both types of clothing. (iii) Mean skin temperatures and skin temperatures in the face, chest, thigh and leg were significantly lower at Ta of 10 degrees C in summer than in winter in clothing A, while skin temperatures in the face and thigh were also significantly lower at Ta of 10 degrees C in summer than in winter in clothing B. (iv) Metabolic heat production was higher in summer than in winter at 20 and 10 degrees C in both types of clothing. (v) The subjects felt cooler and colder to Ta of 10 degrees C in summer than in winter in both types of clothing. These different responses occurring between summer and winter are discussed mainly in terms of total conductance and dry heat loss. PMID- 8468099 TI - Intraocular pressure (IOP) in relation to four levels of daily geomagnetic and extreme yearly solar activity. AB - The link between geomagnetic field activity (GMA), solar activity and intraocular pressure (IOP) in healthy individuals was investigated. The IOP of 485 patients (970 eyes) was recorded over three nonconsecutive years (1979, 1986, 1989) which were characterized by maximal solar activity (1979, 1989) or minimal solar activity (1986). The measurements were also correlated with four categories of GMA activity: quiet (level I0), unsettled (II0), active (III0), and stormy (IV0). Participants were also differentiated by age and sex. We found that IOP was lowest on days of level IV0 (stromy) GMA. The drop in IOP concomitant with a decrease in GMA level was more significant during periods of low solar activity and in persons over 65 years of age. There was a trend towards higher IOP values on days of levels II0 and IV0 GMA in years of high solar activity. Differences between the sexes and among individuals younger than 65 years were not significant. Our results show an interesting aspect of environmental influence on the healthy population. PMID- 8468100 TI - Myocardial infarct death, the population at risk, and temperature habituation. AB - Daily myocardial infarct deaths from Brisbane, 29 degrees 28' S, and Montreal, 45 degrees 30' N, were used to derive a "pool of susceptible individuals". Pool size had no effect on the minimum death temperature but large pools increased the value of the acceleration temperature in Brisbane and the maximum death temperature in Montreal. Moderately sized pools in Montreal appeared to produce reduced death rates in cold conditions from both cold avoidance and habituation. A generalized relationship between temperature and myocardial infarct death is postulated. PMID- 8468101 TI - Photoperiod, temperature, and regional patterns of conceptions in the USA. AB - Twenty-two years of monthly values of birth data for the USA, 1967 through 1988, were analyzed by visual inspection. The data were transformed to remove the influence of length of month and of linear trend, and the values were lagged 9 months to approximate the time of conception. Then, 11-year monthly averages were obtained and plotted as standard scores. Thus two 11-year sets of data were independently analyzed, providing the opportunity of replication. Four distinct temporal patterns were found, differing in month of occurrence of the initial trough and peak and the relative sizes of the two troughs; these characteristics of the temporal pattern change systematically with latitude in the eastern and midwestern states. Data from two other continents, the United Kingdom and Australia, also were analyzed using the same method and found to exhibit a temporal pattern during the year similar to the northern states of the USA. Two biologically relevant variables, temperature and photoperiod, were considered as possible controllers and regulators of the annual rhythmicity. Comparisons of the trends in conceptions with these environmental variables, and inspections of the temperatures and photoperiods at which peaks and troughs in conceptions were found, indicated that these environmental variables could not account for the annual rhythmicity in conceptions. PMID- 8468103 TI - Hypnotizability and facets of openness. AB - Absorption, a correlate of hypnotizability, is related to a broader dimension of openness to experience, one construal of the "Big Five" structure of personality. But openness itself is very heterogeneous, and some of its facets may be unrelated to hypnotizability. A total of 651 subjects completed a questionnaire measuring three different aspects of openness--absorption, intellectance, and liberalism--before receiving the Harvard Group Scale of Hypnotic Susceptibility, Form A. The three dimensions were only modestly related to each other, and only absorption was significantly related to hypnotizability. Adding intellectance and liberalism to absorption did not enhance the prediction of hypnotizability. The results indicate that the various facets of openness are rather different from each other and that the "Big Five" structure may need to be expanded. Absorption and hypnosis share a kind of imaginative involvement that is not necessarily part of other kinds of openness, such as intellectance and liberalism. PMID- 8468102 TI - Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue. AB - The effect was investigated of endurance training on the expression of uncoupling protein (UCP) mRNA in brown adipose tissue (BAT) of rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training programme, a marked decrease in BAT mass was found in terms of weight or weight per unit body weight; there was a corresponding decrease in DNA content and a downward trend in RNA and glycogen levels. The UCP mRNA was present at a markedly decreased level in BAT of trained animals. In consideration of the reduced levels of mRNAs for hormone-sensitive lipase and acyl-CoA synthetase, the brown adipose tissue investigated appeared to be in a relatively atrophied and thermogenically quiescent state. PMID- 8468104 TI - Direct versus indirect suggestions: a conceptual and methodological review. AB - The article reviews the literature on the effects of direct versus indirect hypnotic suggestions. A conceptual and methodological analysis of direct versus indirect suggestions is also provided. Three conclusions follow from the review: (a) Contrary to views of Ericksonian hypnotists, suggestion style has little effect on objective responding to hypnotic test items; (b) studies of clinical- and laboratory-induced pain and other measures of subjective experience have yielded contradictory results--however, the best controlled studies have not indicated that indirect suggestions are superior to direct suggestions; and (c) there is insufficient evidence to conclude that hypnotizability level and suggestion wording interact, such that low hypnotizable subjects are particularly responsive to indirect suggestions. Methodological and conceptual problems in defining and studying hypnotic communications, the lack of rigorous experimental controls, and research issues and directions are highlighted. PMID- 8468105 TI - Response expectancy as a mediator of hypnotizability modification: a brief communication. AB - The role of response expectancy in bringing about increases in hypnotic susceptibility by use of the Carleton Skill Training Program (CSTP) was assessed with 27 subjects selected for their low hypnotizability scores. Subjects were randomly assigned to one of two conditions: 13 received the CSTP to increase their hypnotic susceptibility, and 14 received no training. In addition to assessing hypnotizability, hypnotic response expectancies were assessed before and after training. With pretreatment hypnotizability controlled, subjects in the training group scored significantly higher than control subjects on all self report measures of hypnotizability but not on a measure of observed behavioral response. Changes in response expectancy were found to be highly correlated with changes in hypnotizability. With changes in expectancy controlled, no significant differences between the trained and control groups were found. PMID- 8468106 TI - Hypnotic susceptibility and the endogenous eyeblink: a brief communication. AB - This study investigated the relationship between hypnotic susceptibility, hypnotic state, and the endogenous eyeblink with 36 undergraduates, who were assigned to four independent groups (waking-low, hypnotized-low, waking-high, and hypnotized-high susceptibles) on the basis of combined cutoff scores on both the Creative Imagination Scale and the Stanford Hypnotic Clinical Scale for Adults. The auditory vigilance task required subjects to discriminate between 200 ms and 300 ms tones over a 35-minute period. Hypnotic depth was controlled across trials using the Long Stanford Scale of Hypnotic Depth. As predicted, high-susceptible subjects had a significantly lower blink rate than low-susceptible subjects. The predicted interaction between susceptibility and hypnotic state was also confirmed. High-susceptible subjects showed a significant decrease in blinking for the hypnotized condition, whereas low-susceptible subjects did not. The need for replication with more adequate measures of susceptibility is discussed. PMID- 8468107 TI - Hypnosis and attention deficits after closed head injury. AB - In a controlled study of patients attending a concussion clinic because of ongoing postconcussion symptoms, attention deficits were recorded in the head injured group for the aspects of alertness, assessed by the Continuous Performance Test (CPT), and processing capacity, assessed by a version of the Paced Auditory Serial Addition Test (PASAT). Selective attention was intact. Hypnotizability was assessed by the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A), with normal means and standard deviations found in both the concussed and control groups. There was a significant correlation, however, between HGSHS:A scores and PASAT scores in the concussed group only. The results of this preliminary study suggest that slower processing capacity after a closed head injury may predict higher hypnotizability and that hypnosis could be an appropriate rehabilitation technique for these patients who present with postconcussion symptoms. PMID- 8468108 TI - Iron protein succinylate in the treatment of iron deficiency: controlled, double blind, multicenter clinical trial on over 1,000 patients. AB - A prospective, controlled, double-blind, double-dummy, multicenter clinical trial was made to assess the efficacy and tolerability of iron-protein-succinylate (ITF 282) in comparison with a well known iron preparation in the treatment of iron deficiency or iron deficient anemia. One thousand and ninety-five patients affected with iron deficiency or overt iron deficient anemia were randomized to receive either two ITF 282 tablets/day (60 mg iron each) or a commercially available ferrous sulphate controlled release tablet (one tablet containing 105 mg iron/day). Five hundred and forty-nine patients received ITF 282; 546 patients were treated with ferrous sulphate. Both treatments lasted 60 days. The treatment outcome was checked by evaluating special hematology, symptomatology, safety hematology and hematochemistry. After two months of treatment, the normalization of the main hematologic parameters in both groups was detected. Although in the first month the reference treatment appears to provide somewhat faster results, at the end of the observation, the values of hematocrit, hemoglobin and ferritin were greater in the ITF 282 group, indicating a more progressive and steady therapeutic effect. The overall clinical rating was significantly in favor of ITF 282, with 78.9% of favorable results vs 67.6%. By dividing the patient population according to pathological conditions (iron deficiency or overt anemia), or according to the etiopathogenesis of the iron deficiency (increased requirement, or increased loss in adults and in the elderly), separate analyses on the treatment outcome were made (and have been included). The general tolerability, although favorable with both treatments, was significantly more favorable with ITF 282. With this medication, 63 patients (11.5%) complained of 69 adverse reactions (25 heartburn, 19 constipation, 25 abdominal pain) vs 141 events reported by 127 patients (26.3%) with the reference medication (33 heartburn, 31 epigastric pain, 23 constipation, 32 abdominal pain, 8 skin rash, 14 nausea). These observations confirm that, although the most modern preparations of ferrous sulphate exhibit a relatively low frequency of adverse events of limited clinical concern, it is nevertheless possible to decrease both the prevalence and the duration of such events without prejudice for the clinical efficacy, with the use of more "physiological" preparations in which the iron is reversibly bound to a protein carrier, thus effectively removing one of the main obstacles to the correct compliance with treatments that must be administered for prolonged periods of time. PMID- 8468109 TI - Effect of hydroxyzine and meperidine on arterial blood gases in patients with chronic obstructive pulmonary disease. AB - Hydroxyzine is frequently used to tranquilize chronic obstructive pulmonary disease patients, who may be concomitantly receiving narcotic analgesics. Therefore, its effect alone and in combination with meperidine on arterial blood gases and ventilation at rest were evaluated in 44 patient volunteers, who gave informed consent. Hydroxyzine, 1.5 mg/kg i.v. caused no significant decrease in PaO2 and pH, no increase in PaCO2 at 5, 10, 20, 30 and 60 min post-infusion (n = 13, mean age = 63.4 years). Meperidine, 1.5 mg/kg i.v. caused a significant (p < 0.001) reduction in PaO2 for 20 min with concomitant increase in PaCO2 (n = 14; mean age = 49.4 years). The combination of the same doses of hydroxyzine with meperidine i.v. caused no greater decrease in PaO2 or in pH or increase in PaCO2 than did meperidine alone (n = 17; mean age = 52.6 years), indicating no greater ventilatory depression with the combination than with meperidine alone. The lack of significant pH decreases at 30 and 60 min further corroborates no potentiation of meperidine by hydroxyzine. In conclusion, hydroxyzine, even when given through the i.v. route in excess of the maximum i.m. therapeutic dose, caused no changes in PaO2, PaCO2 or pH in chronic obstructive pulmonary disease patients. Therefore, its i.m. administration resulting in lower blood levels than i.v., is not likely to cause ventilatory depression. Furthermore, hydroxyzine caused no potentiation of the ventilatory depression induced by meperidine, hence hydroxyzine may be safely employed in combination with meperidine. PMID- 8468110 TI - The antimicrobial actions of taurolin and other preparations on the pathogenic spectrum in dentoalveolar infections. AB - Bacteriological specimens from a total of 64 patients with six common, highly relevant clinical indications were collected for an in vitro investigation. By means of standard microbiological methods, 149 species of organism were differentiated, and their relative sensitivity to Taurolin, a broad spectrum chemotherapeutic and antitoxin, as well as 5 conventional finished pharmaceuticals were tested in agar diffusion tests. Taurolin, which was tested in 3 different galenic formulations, produced practically identical, but considerably wider zones of inhibition than all other compared products. In contrast to other substances which exhibited a failure rate of up to 24.8%, no gaps in the activity spectrum in the form of the lack of inhibition zone formation were observed. PMID- 8468111 TI - Heparin-induced transaminase elevations: a prospective study. AB - An intensive and prospective surveillance study of 54 patients hospitalized in the Internal Medicine Unit of Clinical Hospital of the Catholic University of Chile, who required heparin in the period between June and December of 1991 was done. The aim of the work was to characterize and study the incidence of the adverse reactions associated with heparin therapy, with special emphasis on abnormal serum transaminase elevation. Abnormal transaminase elevation was defined as a rise over 20% of the serum transaminase baseline value. For determining the serum transaminase level, a UV spectrophotometric method was used. The incidence of the adverse drug reactions (ADR) was 24.1% (13 ADR), 8 of which (14.8%) were related with heparin therapy. Three of them (5.5%) corresponded to alanine transaminase (ALAT) increase and five (9.3%) to aspartate transaminase (ASAT) elevation. By means of global introspection method, 3 cases of ALAT increases were defined as probable and 6 as possible, while 5 ASAT increases were estimated as probable and 14 as possible. All of them were of slow onset, did not require treatment and hospital stay was not prolonged. Two patients' characteristics--age and sex--were associated with the development of heparin-induced abnormal alanine transaminase concentrations. The younger male patients showed a greater frequency of heparin-induced ALAT elevation. However, this association was not observed with the heparin-induced ASAT increase. These reactions were dose-dependent. Patients with heparin-induced ALAT elevation received a dose of 154,220 IU +/- 72,970 IU in comparison to patients without that adverse reaction who received 96,210 IU +/- 40,340 IU. This difference was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468112 TI - Comparison of fluorescence polarisation immunoassay (FPIA) and high performance liquid chromatography (HPLC) methods for the measurement of flecainide in human plasma. AB - The precision and accuracy of HPLC and FPIA for the measurement of flecainide plasma levels were compared below, in and above the therapeutic range (200-1,000 ng/ml). Following a calibration crossover study, five standard plasma solutions of varying flecainide concentrations (SPS) and 99 flecainide containing plasma samples of 24 in-patients (IPS) were analyzed with both methods. The results show that within the range of approximately 500-1,500 ng/ml, the two methods did not differ in either precision (expressed as coefficient of variation, CV) or accuracy (expressed as relative error, RE). Close to the lower limit and below the therapeutic range however, HPLC provided greater precision and accuracy than FPIA. PMID- 8468113 TI - Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects. AB - Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2 hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3' position of cephem group instead of NMTT and an extensive modification of 7 beta acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468114 TI - Comparison of the efficacy and safety of amikacin once or twice-a-day in the treatment of severe gram-negative infections in the elderly. AB - The aim of this study was to compare the efficacy and safety of amikacin given either as single injection or as two injections within 12-h interval in the treatment of severe gram-negative infections in elderly patients. Thirty-nine non selected consecutive patients of a general internal medicine facility were randomized to receive the same total daily dose of amikacin either as a single dose (19 patients) or divided into two doses injected at 12-h interval (20 patients). Amikacin was used alone or in combination with metronidazole, clindamycin, fosfomycin or a beta-lactam. Clinical and bacteriological responses were satisfactory and comparable in the two groups. There was no difference between the once/day and the twice-a-day groups with respect to drug dosage, duration of therapy and concomitant treatment. Only one patient (BID group) showed a rise of serum creatinine during the observation period. Amikacin alone or in combination can be regarded as an efficacious and safe antibiotic in the treatment of severe gram-negative infections in elderly patients, whether the daily dose is administered in a single infusion or in a BID interval. PMID- 8468115 TI - Effects of SK&F 105685, a novel anti-arthritic agent, on immune function in the dog. AB - SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-propanamine+ ++ dihydrochloride) is a novel azaspirane with beneficial activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental encephalomyelitis in the Lewis rat and lupus-like disease in the MRL mouse. The activity of SK&F 105685 in these models is associated with the induction of non specific suppressor cell (SC) activity as defined by the ability of cells from drug-treated animals to inhibit the proliferative response of lymphocytes from control animals to concanavalin A. To evaluate the immunotoxicologic potential of SK&F 105685, the effect on immune function of one month of dosing with 1 mg/kg/day of SK&F 105685 was examined in the dog. Differential blood cell counts and ex vivo immune function assays were performed using blood collected before dosing on days 1 (baseline), 15 and 29, of the study. Immune function assays were performed on spleen cells on day 30. Under the conditions of the study, SK&F 105685 displayed pharmacological activity as demonstrated by the induction of splenic SC activity. The drug did not affect the total number or relative percentages of the various white blood cell types present in peripheral blood and did not cause generalized immunosuppression. The ability of peripheral blood lymphocytes or spleen cells to produce IL-2 or proliferate in response to mitogenic stimulation was not affected by drug treatment. SK&F 105685 also failed to affect the candidacidal activity of polymorphonuclear leucocytes and spleen cells indicating that it is unlikely to compromise nonspecific resistance to infection. SK&F 105685 however, was able to inhibit the generation of a specific in vitro antibody response to sheep red blood cells (SRBC) by splenocytes from treated animals. Inhibition of the anti-SRBC antibody response was also observed upon addition of the drug to normal spleen cells. Addition of the drug at different time points during the culture period indicated that SK&F 105685 was interfering with an event(s) occurring during the first 72 h of culture. Taken together, these results suggest that, in a therapeutic setting, SK&F 105685 is unlikely to compromise the immune status of the host as it can down-regulate a specific immune response without causing generalized immunosuppression. PMID- 8468116 TI - Combined treatments with interferon (alpha,beta) plus PGA1 to control early infection with HTLV-I in primary cord blood-derived mononuclear cells. AB - Interferon (IFN) alpha and beta can activate an antiviral and immunomodulating response in primary cord blood-derived mononuclear cells (CBMC) exposed to infection with Human T-cell Leukemia Virus type I (HTLV-I), resulting in partial inhibition of early infection in vitro. On the other hand, PGA1, a PGE1-derived cyclopentenone prostaglandin, can inhibit in vitro the proliferation of virus infected CBMC, preventing the emergence of the potentially transformed clone. In order to achieve a complete control of HTLV-I infection in this experimental model, we evaluated whether the antiviral activity of IFNs and the antiproliferative activity of PGA1 could be preserved in a combination therapy scheme. Recipient CBMC were treated with IFN alpha or beta (1000 IU/ml) at the onset of the co-culture with lethally irradiated virus-donor MT-2 cells, followed by multiple treatments with PGA1 (4 micrograms/ml every 4 days, starting on day 0) for 6 weeks post infection (p.i.). In PGA1-treated co-cultures the percentage of virus-positive CBMC was constantly doubled during culture time as well as the amount of viral transcripts and p19 virus core protein production were increased. The antiviral effects of IFNs, resulting in about a 50% reduction of the percentage of virus-positive CBMC and consequently in a partial inhibition of virus expression (HTLV-I transcription and p19 production) until 4 weeks p.i., were suppressed by multiple PGA1 treatments. However, the antiproliferative effect of PGA1 was enforced in IFN-treated co-cultures, leading to earlier control of proliferation of virus-infected cells. Interestingly, infection of CBMC with HTLV-I was associated with persistent expression of 70 kDa heat shock protein (HSP70), for at least 4 weeks p.i. IFNs and PGA1 showed antagonistic effects on HSP70 production in infected CBMC. In fact, production of HSP70 was suppressed (or prevented) in IFN-treated co-cultures, tested 2 and 4 weeks p.i. The fact that the expression of HSP70 is apparently suppressed (or prevented) by IFN treatment is surprising, since expression of this protein family has been associated with antiviral immunity. PGA1 could totally reverse the IFN-mediated suppression of HSP70 expression in these co-cultures. It is presently unclear whether HSP70 expression is directly involved in the control of proliferation exerted by PGA1 against virus-infected CBMC or is an epiphenomenon associated with inhibition of cell growth. PMID- 8468117 TI - Pharmacokinetics of an immunomodulator peptidoglycan monomer in mice after intravenous administration. AB - A 14C labeled low molecular weight immunomodulator, peptidoglycan monomer (14C PGM), was injected intravenously (i.v.) into mice. At various time intervals thereafter (15 min-6 h), radioactivity in the urine, whole blood, plasma, kidneys, liver, spleen, lungs, intestines and the brain of the mice was determined. Shortly after injection, 14C-PGM was very rapidly excreted from the organism, so that 1 h following administration, 80% of the radioactivity was found in the urine (62% as unchanged PGM and the rest as the metabolites pentapeptide and disaccharide). At the same time, around 2% of the injected material was found in the blood. Six hours after injection, equal quantities were found in the intestines, liver and blood (0.5%), slightly less in the kidneys, lungs and spleen (0.2-0.3%) and the least quantity in the brain (0.04%). However, the dynamics of retention in the organs was evidently different. In the kidneys, lungs and spleen, radioactivity steadily decreased over the studied period. In the liver following an initial decrease, radioactivity remained the same 3 and 6 h after injection. On the other hand, in the intestines and brain PGM seemed to accumulate rather than disappear following i.v. administration. This fact should be considered when explaining different biological activities of low molecular weight bacterial peptidoglycans. PMID- 8468118 TI - Murine systemic autoimmune disease induced by mercuric chloride (HgCl2): Hg specific helper T-cells react to antigen stored in macrophages. AB - The adoptive transfer popliteal lymph node assay (PLNA) was used to demonstrate Hg-specific T-cell responses of mice that were continuously treated with HgCl2 by a regimen known to induce a systemic autoimmune disease in H-2s (murine histocompatibility complex, haplotype s) mice, but not H-2d mice. We found that spleen cells of B10.S and A.SW donors (both H-2s) responded anamnestically to HgCl2 by inducing a significant increase in cellularity in the draining PLN of the recipient: In contrast, spleen cells of HgCl2-treated DBA/2 (H-2d) donors failed to induce an increase in PLN cellularity, and spleen cells of B10.D2/n (H 2d) donors induced no changes or even diminished PLN cellularity upon re encounter with HgCl2. Kinetic studies showed that spleen cells of B10.S donors were stimulatory from day 3 until day 14 of donor HgCl2 treatment and, when purified splenic T-cells were tested, still on day 28, the last point in time tested. The Hg-specific T-cells prepared from HgCl2-treated B10.S mice not only induced an increased cellularity, but also B-cell activation to antibody secretion in the draining PLN of the recipient. Moreover, the Hg-specific donor T cells transferred could specifically be restimulated by killed peritoneal cells obtained from the same donors or from syngeneic donors previously treated with HgCl2. Interestingly, when killed peritoneal cells were injected as antigen the amount of Hg required for T-cell restimulation was only 1/40 of that required when free HgCl2 was used. Taken together, these results show that an HgCl2 treatment schedule designed to induce systemic autoimmune disease primes Hg specific T-helper (Th) cells and generates immunogenic material in peritoneal cells to which the T-cells react. The possible contribution to the pathogenesis of HgCl2-induced auto-immune disease of these Hg-specific T-cells and the autoreactive T-cells reported in the literature is discussed. PMID- 8468119 TI - Comparative effects of tetrandrine and berbamine on guineapig airway microvascular leakage induced by platelet-activating factor and other allergic mediators. AB - The bisbenzylisoquinoline analogues, tetrandrine and berbamine, were investigated for their effects on guineapig airway microvascular leakage, an animal model of asthma and allergic inflammation. Significant inhibition of microvascular leakage by tetrandrine was observed with all four allergic mediators used in these experiments. By contrast, berbamine was able to suppress microvascular leakage induced by platelet-activating factor and bradykinin, but not by leukotriene D4 or histamine. These results indicate that tetrandrine has broad-spectrum inhibitory activity on allergic mediators, and may have value for the therapy of diseases in which these mediators have a role in pathogenesis. PMID- 8468120 TI - Cytotoxic effect of ricin A-chain conjugates containing monoclonal antibodies against human erythroid cells. AB - Selective elimination of human erythroblastoid cells by the conjugate of the A chain of a plant toxin ricin (RA) and monoclonal antibody (MAb) HAE9 (IgM) directed against human erythroblast antigen (Ag-Eb) has been demonstrated. In comparative experiments, MAb HAE3 (IgM) against human glycophorin-A was used. On average, the conjugates obtained contained two A-chain molecules and one antibody molecule. Efficiency of cytotoxic action of native ricin and conjugates was compared both with the amount of binding sites on the surface of K562 cells and the internalization rate of these proteins. The association constants of the proteins proved to be almost the same (ka = 10(8) M-1). The ID50 values were 1.1 x 10(-11), 3.2 x 10(-10) and 3.1 x 10(-9) M for ricin, HAE9/RA and HAE3/RA, respectively. Ammonium chloride at a concentration of 10 mM increases the cytotoxic effect of the HAE9/RA conjugate approximately 10 times and does not change the activity of the HAE3/RA conjugate. PMID- 8468121 TI - Enhancement of various non-specific immune effector functions in mice by local injection of aclacinomycin A adsorbed onto activated carbon particles (ACR-CH). AB - Local injections of aclacinomycin A adsorbed onto activated carbon particles (ACR CH) augmented the cytotoxic activities of regional lymph node cells for 7 days. In contrast NK-activity was only slightly augmented by injections of aclacinomycin A (ACR) solution or activated carbon suspension. The effects were found in lymphocytes from all regions tested. NK-activity could only be detected when both adherent and non-adherent cells were present. The cell number of L3T4+ cells in each type of lymph node tested increased, and subset analysis of the lymphocyte subpopulations revealed an increase in the ratio of L3T4+/Lyt2+ cells, suggesting that the ACR-CH selectively increased and stimulated L3T4+ cells. Enhanced capacity of lymph node cells to produce cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1) upon restimulation (with LPS) in vitro in the ACR CH treated group was found. From these results, it appears that the new dosage form of aclacinomycin A, ACR-CH, with superior therapeutic efficacy against lymph node metastases, can also enhance the immune response of regional lymph node cells. The findings reported here will be valuable in the establishment of novel chemoimmunotherapeutic protocols using ACR-CH. PMID- 8468122 TI - Cyclophosphamide blocks both antigen-specific and polyclonal immunoglobulin responses in experimental visceral leishmaniasis. AB - Cyclophosphamide (Cy) has been shown to modulate antibody responses in a wide range of diseases both in humans and experimental animals. Our results in Syrian hamsters infected with Leishmania donovani have shown that Cy blocks specific and polyclonal antibody production both in vivo and in vitro. This effect was achieved by weekly 100 mg/kg doses and also by a 300 mg/kg single dose. Although Cy provokes a significant decrease in B-cell numbers in infected animals, this cannot explain the suppression of antibody production since a 50% decrease in B cells of only-infected hamsters did not reproduce the same effect in in vitro assays. Also, this suppression was not reversed either by elimination of adherent cells or by the presence of indomethacin. These data suggest that Cy affects T cell populations involved in the control of antibody production by B-cells. PMID- 8468123 TI - Comparison of dideoxynucleoside drugs (DDI and zidovudine) and induction of hematopoietic toxicity using normal human bone marrow cells in vitro. AB - The drug zidovudine (AZT), a synthetic thymidine analog, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced hematopoietic toxicity manifested by anemia, neutropenia and on occasion thrombocytopenia. Such toxicity has stimulated the development of alternative dideoxynucleoside drugs capable of exerting anti-viral potency while minimizing the risk for inducing organ toxicities. One such alternative dideoxynucleoside drug is 2',3'-dideoxyinosine (ddI). Recent therapeutic anti viral strategy, now undergoing clinical trial, is the evaluation of combined zidovudine ddI treatment. Unfortunately a complete assessment of their potential toxicity using this drug regimen has not been thoroughly examined. We report here the results of studies comparing the toxicity profile of zidovudine versus ddI on their ability to influence several classes of hematopoietic progenitor stem cells, e.g. granulocyte--macrophage (CFU-GM), megakaryocyte (CFU-Meg) and erythroid (CFU-E/BFU-E) following in vitro co-culture with normal human bone marrow. Since the main clinical toxicity associated with zidovudine in vivo is the development of anemia, additional in vitro studies compared the dose escalation effect of erythropoietin in the presence of combined zidovudine and ddI. CFU-GM, CFU-Meg, CFU-E and BFU-E were all reduced (P < 0.05) following incubation with either zidovudine or ddI thus determining their ID50 concentrations for these classes of hematopoietic progenitors; however, the extent of toxicity associated with ddI was lower than what was observed with zidovudine. More importantly, dose-escalation of erythropoietin was effective in reversing the inhibition observed for ddI on erythroid progenitors CFU-E and BFU E (P < 0.05), an effect not reported with zidovudine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468124 TI - Expression of activation markers on peripheral-blood lymphocytes following oral administration of Bacillus subtilis spores. AB - This study was undertaken to assess the capability of Bacillus subtilis spores to modify the peripheral-blood lymphocyte (PBL) subsets or determine the de novo expression of activation markers. The data we obtained show that spores of B. subtilis are able to increase the expression of certain cell activation markers and that such activation is dose-dependent. In fact, doses of 2 x 10(9) spores did not give rise to changes in any of the parameters evaluated, while doses of 6 x 10(9) increased the HLA-DR antigen expression on T-lymphocytes. At the highest dosage used (12 x 10(9), B. subtilis spores caused the appearance of cells bearing the CD25 and CD71 activation markers. Therefore, such cell activation markers may prove useful for monitoring the activity of B. subtilis spores, and possibly of other immunomodulating agents, in the course of clinical research. PMID- 8468125 TI - Three sibling species within Contracaecum osculatum (Nematoda, Ascaridida, Ascaridoidea) from the Atlantic Arctic-Boreal region: reproductive isolation and host preferences. AB - Genetic variation within and between population samples from 22 locations of the Atlantic Arctic-Boreal region, including 1657 specimens morphologically assigned to Contracaecum osculatum, was electrophoretically analysed at 17 loci. Highly significant deviations from the Hardy-Weinberg equilibrium were found at various loci in several samples, owing to the existence of three distinct gene pools within C. osculatum (sensu lato) from the study area. These gene pools correspond to three biological species (provisionally designated A, B and C), characterized by distinct genotypes at several diagnostic loci. Reproductive isolation between C.osculatum A, B and C is confirmed by the lack of F1, recombinant, or backcross genotypes in sympatric areas, despite the occurrence of multiple infections. Mean heterozygosity per locus is on average 0.11 in species A, 0.10 in B and 0.07 in C. High levels of gene flow were found within each of the three species, the values of Nm (number of migrant individuals) ranging from 3.41 (C. osculatum C) to 5.77 (C. osculatum A). Average Nei's genetic distance is 0.46 between A and B, 0.50 between A and C and 0.77 between B and C. From these values, times of evolutionary divergence from 2 to 4 million years can be estimated. Genetic relationships among populations and species of the C. osculatum complex are illustrated by principal component analysis. The role of both geographical isolation and host preferences in the speciation of C. osculatum (sensu lato) is discussed. A morphological distinction of the three species has not yet been possible (sibling species). However, there is evidence that the name C. osculatum (sensu stricto) should be used for species C, which shows a geographical distribution and definitive host corresponding to the neotype of C. osculatum (sensu stricto). Finally, a comparison is made between the members of the C. osculatum complex from the Atlantic Arctic-Boreal region and those of the Pseudoterranova decipiens complex from the same area, as to: (i) times of evolutionary divergence, (ii) geographical distribution, and (iii) host preferences. PMID- 8468126 TI - Does the duration of antigen retention in draining lymphoid tissue following GI nematode infection determine the 'responder phenotype' of the host? PMID- 8468127 TI - Topical treatment of cutaneous leishmaniasis in Belize: in vitro and in vivo studies with Leishmania mexicana. AB - Strains of Leishmania mexicana isolated from Belizian patients were found to be highly susceptible to paromomycin sulphate (PR) treatment. This drug at 100 micrograms ml-1 destroyed 85-99.5% of in vitro cultivated Leishmania promastigotes within 4 days of exposure to the drug. Leishmania promastigotes inoculated into the base of the tail of Balb/c mice caused the development of local lesions several weeks after infection. These lesions were totally cleared of parasites after 20 days of topical treatment with PR ointment, comprised of 15% paromomycin sulphate and 12% methylbenzethonium chloride in soft white paraffin. Similar results were also obtained with L. braziliensis infections. Isoenzyme analysis was found to be the method of choice for parasite strain identification. Excreted factor serotyping was only partially effective and promastigote agglutination gave negative results. PMID- 8468128 TI - Lipids in the broodsac of Leucochloridium variae (Digenea, Leucochloridiidae) and its snail host Succinea ovalis. AB - Thin-layer chromatographic analysis was used to examine lipophilic pigments and neutral lipids in the broodsac of Leucochloridium variae and in the tissues of its snail host, Succinea ovalis. Beta-carotene and lutein were not detected in either the parasite or the host on a C-18 reversed phase layer developed in a solvent system of petroleum ether-acetonitrile-methanol (2:4:4). This chromatographic system was able to detect 10 ng of a beta-carotene standard and 100 ng of a lutein standard. The Mangold solvent system on a silica gel plate showed the presence of triacylglycerols, free sterols, and sterol esters as the major neutral lipids in both snail and parasite tissues. As seen in a previous sporocyst-snail relationship, the qualitative neutral lipid profiles of both host and parasite are similar. PMID- 8468129 TI - The Bo-RBC-SCID mouse model for evaluating the efficacy of anti-theilerial drugs. AB - We have previously developed a mouse model which allowed the proliferation of Theileria sergenti in severe combined immunodeficiency (SCID) mice with circulating bovine erythrocytes (Bo-RBC). In the present study, this model was utilized to test the efficacy of anti-theilerial drugs. Bo-RBC-SCID mice were created by giving periodic transfusions of T. sergenti-free Bo-RBC, and subsequently infecting with T. sergenti. Three anti-protozoal compounds, Pamaquine (Yamanouchi Pharmaceutical Co. Ltd), Ganaseg (Japan CIBA-GEIGY Ltd) and Buparvaquone (Coopers Animal Health Ltd), were subcutaneously administered into the mice at doses recommended for cattle therapy. Blood examinations demonstrated that all three drugs significantly reduced the level of parasitemia although Ganaseg was effective only at a dose five times higher than that recommended for cattle therapy. Administration of the drugs neither caused any sign of acute toxicity nor changed the rate of Bo-RBC in the SCID mice's circulating blood cells. The results indicate that the Bo-RBC-SCID mouse model may offer a useful in vivo system for evaluating the efficacy of anti-protozoal drugs against T. sergenti. PMID- 8468130 TI - Identification and purification of Cooperia oncophora-specific antigens to improve serological diagnosis. AB - Cooperia oncophora total adult extracts were examined by Western blotting with sera from C. oncophora- and O. ostertagi-infected calves to determine species specific antigens. It was shown that two antigens with apparent molecular weights of 14.2 and 14.9 kDa were only recognized by calves which received a Cooperia infection and not by Ostertagia mono-infected calves or parasite-naive animals. The partial purification of these two antigens was achieved by gel filtration and ion-exchange chromatography. An enzyme-linked immunosorbent assay (ELISA) was developed based on the fractions containing these two antigens and no cross reactivity could be noticed with serum from Ostertagia mono-infected calves. In contrast, the ELISA with total worm extracts showed strong cross-reactivity with heterologous serum. It was concluded that the 14.2 and 14.9 kDa Cooperia adult antigens have diagnostic potential, at least to differentiate C. oncophora and O. ostertagi. PMID- 8468131 TI - Identification of a Babesia bovis gene with homology to the small subunit ribosomal RNA gene from the 35-kilobase circular DNA of Plasmodium falciparum. AB - Isolation of a 552-base pair (bp) fragment of a putative extrachromosomal small subunit ribosomal RNA (SSrRNA) gene from Babesia bovis was achieved using the polymerase chain reaction (PCR) followed by cloning and sequencing of the PCR product. The sequences of the oligonucleotide primers used for the PCR were derived from selected known sequences in the organellar SSrRNA gene which is encoded within the 35-kilobase (kb) circular DNA from Plasmodium falciparum. Comparison of the sequence of the 552-bp fragment from B. bovis with gene sequences from other organisms showed 71% identity with the organellar SSrRNA gene from P. falciparum and up to 65% identity with the plastid SSrRNA gene sequences from various other organisms. We conclude that the 552-bp fragment amplified by PCR from B. bovis is possibly derived from an organellar genome of this parasite. PMID- 8468132 TI - Analysis of the 18S ribosomal RNA gene of Strongyloides stercoralis. AB - The entire 1766 bases of the 18S rRNA gene of Strongyloides stercoralis have been sequenced. The gene has a 38% G+C content. Although it is similar in length to the 18S rRNA gene of Caenorhabditis elegans, the only other completely sequenced nematode 18S rRNA gene, it is only 69% identical. Closely related helminths will need to be sequenced in order to delineate sequences specific for the diagnosis of strongyloidiasis. PMID- 8468133 TI - Sibling species within Macropostrongyloides baylisi (Nematoda: Strongyloidea) from macropodid marsupials. AB - Macropostrongyloides baylisi from four different species or subspecies of host were analysed electrophoretically at 27 enzyme loci. The results revealed the existence of two species, one in Macropus giganteus and the other in M. robustus robustus, M.r. erubescens and M.r. parryi, that had fixed genetic differences at 33% of loci. Populations of nematodes from two subspecies of M. robustus, M.r. robustus from Queensland and M.r. erubescens from South Australia, had fixed genetic differences at two (7.4%) of 27 loci and were considered to belong to the same species. No fixed genetic differences were detected between nematodes from M. parryi and M.r. robustus. A discriminant function analysis of morphological data assigned 96% of specimens to groups defined on the basis of the host species or subspecies from which they were obtained. This separation of Ma. baylisi into host-specific groups did not, however, totally correlate with the electrophoretic data. The species of M. baylisi in M. giganteus was genetically more distinct from the sibling species in M. robustus/M. parryi than to a related but morphologically dissimilar nematode, Ma. yamagutii from M. fuliginosus. This suggests an evolutionary parallel between host and parasite at the genetic level which is not reflected by morphological differences. PMID- 8468134 TI - Oxygen affinities of metronidazole-resistant and -sensitive stocks of Giardia intestinalis. AB - The common protozoon, Giardia intestinalis, parasitizes the upper small intestine of man, and is often refractory to treatment by metronidazole. Defective oxygen scavenging mechanisms have been implicated as a cause of metronidazole resistance of another flagellate Trichomonas vaginalis, where metronidazole is also the most common drug treatment. Oxygen consumption of six clinical isolates of G. intestinalis and one line selected for resistance to metronidazole was measured over 0-50 microM-O2 using an oxygen electrode open for gas exchange. At > 30 microM-O2, inhibition of respiration was demonstrated in all seven stocks. Apparent oxygen affinities (KmO2) were found to range from 0.5 to 5.2 microM-O2; however, isolates from patients who failed to respond to treatment with metronidazole did not have measurably defective O2-scavenging capabilities compared with metronidazole-sensitive isolates. These strains did, however, show elevated NADPH-oxidase activities compared with metronidazole-sensitive strains. Results indicate that biochemical mechanisms of drug resistance in G. intestinalis may be quite different from those operating in T. vaginalis. PMID- 8468135 TI - Identification of host-protective antigens of Taenia ovis oncospheres. AB - Sheep were fully protected against challenge infection following immunization with a homogenate of T. ovis oncospheres. Ultracentrifugation of sonicated oncospheres either alone or in the presence of a range of detergents did not reduce the immunogenicity of the extracts. Solubilization of oncosphere extracts in non-ionic detergents or sodium dodecyl sulphate (SDS) enabled analysis of host protective antigens by isoelectric focusing (IEF) and electrophoresis in polyacrylamide gels (SDS-PAGE), respectively. Immunoblotting analysis of oncosphere antigens with immune sheep sera identified predominantly two groups of antigens with relative mobilities of 31-34 kDa and 47-52 kDa with a common isoelectric point of 5.8. The immunogenicity of these antigens was confirmed in vaccination trials using appropriate fractions cut from SDS-PAGE gels and agarose IEF gels. Affinity-purified antibodies prepared against the candidate antigens were used to select the corresponding recombinant DNA-derived polypeptides, one of which was subsequently found to be host-protective. PMID- 8468136 TI - Lymphokine production by mesenteric lymph node cells from BALB/C mice during Hymenolepis nana infection. AB - Mesenteric lymph node cells (MLNC) prepared from BALB/c mice during infection with Hymenolepis nana proliferated extensively when cultured in the presence of soluble egg antigen, as assessed by measuring 3H-thymidine incorporation. Analysis of Hymenolepis-specific proliferative cells in MLNC by using monoclonal antibody specific for mouse T lymphocyte surface antigens revealed that the proliferative response of MLNC was mediated by Thy-1.2+, L3T4+ cells, that is, helper T cells. Supernatant of MLNC cultured with egg antigen contained large amounts of interleukin-2 and interferon-gamma, but only low levels of interleukin 5. The titer of these cytokines did not correlate with the interval between oral infection and collection of MLNC. These results strongly indicate that the Th1 subtype of helper T lymphocytes respond well to stimulation of H. nana egg antigen and suggest that acute inflammatory responses are involved in host protective immunity to H. nana. PMID- 8468137 TI - The effects of changes in the definitive host environment on the metabolism of Hymenolepis diminuta during growth and maturation. AB - Flexibility in the metabolism of Hymenolepis diminuta is associated with changing intrinsic requirements during maturation but is also influenced by extrinsic factors, that is, by the nature of the host environment. End-products of carbohydrate metabolism and enzyme activities in worm extracts were used as indicators of metabolic regulation in H. diminuta recovered at various times postinfection. The predominant end-product from 6-day-old worms is lactate, generated by cytosolic glycolysis. As the cestode matures in the host, lactate production by the whole worm decreases and greater amounts of the mitochondrial end-products, succinate and acetate, are detected. A stable, dichotomous carbon flow to lactate, succinate and acetate is observed from 12 days post-infection. A metabolic gradient along the length of individual strobila is also evident. It extends from glycolysis, in the anterior region, to mitochondrial dismutation in the posterior region. The transition from cytosolic to mitochondrial pathways during maturation and along the strobilus is delayed or suppressed in worms recovered from immunosensitized hosts. Four host environments were compared: unsensitized rats, rats immunosensitized with a primary infection of H. diminuta, rats immunosensitized with a primary infection of Nippostrongylus brasiliensis and mice concurrently infected with Heligmosomoides polygyrus. The specific activities of PK and PEPCK in whole worm extracts were similar in 10-, 21- and 35 day-old worms and did not differ in worms isolated from different host environments. However, the PEPCK/PK ratio is high in worms that utilize mitochondrial pathways and low in worms that produce predominantly lactate. LDH activity is high in lactate producers. It is concluded that the pattern of metabolism in H. diminuta is influenced by many effectors in the host environment. PMID- 8468138 TI - Virus-like particles in a monogenean (Platyhelminthes) parasitic in a marine fish. AB - In Microcotyle sp., a gill parasite in the marine fish Abudefduf analogus near Dakar, Senegal, various organs were studied by transmission electron microscopy. One of the six worms studied contained virus-like particles located only in the outer layer and in the cytons (deep cell bodies) of the tegument. The tegument ultrastructure is described for both healthy and infected monogeneans. The outer layer of the tegument, 2-5 microns thick, does not have microvilli. The virus like particles are cytoplasmic, about 70 nm in diameter with a single-layered capsid-like structure 10-12 nm thick, and have an icosahedral symmetry. They originate from viroplasms and accumulate in paracrystalline arrays up to 1 micron in size. By their ultrastructural characteristics, these virus-like particles are related to the Reoviridae or, more probably, the Birnaviridae. This is the third report of viruses in monogeneans, and the first in a polyopisthocotylean monogenean. It is hypothesized that monogeneans could act as vectors of viral diseases among their host fishes. PMID- 8468139 TI - Proliferation of Theileria annulata and Theileria parva macroschizont-infected bovine cells in scid mice. AB - Theileria annulata and Theileria parva macroschizont-infected bovine cells formed tumours at the inoculation site when injected subcutaneously into C.B.-17 scid mice. T. annulata tumours showed more vigorous growth than T. parva tumours. The tumours did not regress and infected cells spread to other tissues. Intraperitoneal injection of high doses of T. annulata-infected cells resulted in the development of ascites: the infected cells colonized abdominal organs, in particular mesenteric tissue. Low doses of cells did not establish when administered by this route. Evidence for a role for macrophages in controlling proliferation of Theileria-infected cells was provided by finding (i) that uninfected bovine cells did not survive for as long in the peritoneal cavities of scid mice as in Balb/c mice: (ii) peritoneal macrophages both proliferated in vivo in the presence of infected cells and were activated as assessed by production of interleukin-1. Evidence against a role for NK cells was provided by (i) the failure of an in vivo assay for allogeneic lymphocyte cytotoxicity to reveal any activity against bovine cells in the lungs or liver, i.e. the sites usually associated with NK cell cytotoxicity, and (ii) the lack of correlation between tumour regression and NK cell activity in the spleens of mice with chronic T. annulata tumours. PMID- 8468140 TI - The effect of cobalt-60 irradiation on the infectivity of Toxoplasma gondii. AB - Toxoplasma gondii cysts in the tissues of experimentally infected mice and pigs were irradiated with cobalt-60 at various doses and used to infect mice and kittens. Loss of parasite infectivity was confirmed following irradiation whereas control animals inoculated with non-irradiated infected tissues became infected. Experiments were repeated to calculate the minimal effective dose (MED) of irradiation to eradicate parasite infectivity. The MED for the Chinese NT strain and the American ME-49 and TS-2 strains of T. gondii cysts in mouse and pig tissues was approximately 0.6 kGy. The infectivity for mice of NT strain bradyzoites irradiated at a dose of 0.45 kGy was reduced 10,000-fold. Such irradiation may be valuable in practical operations to control T. gondii in pork products. PMID- 8468141 TI - Phosphorus metabolites of liver from mice infected with Hymenolepis microstoma. AB - 31P NMR in vivo spectra of mouse livers infected with Hymenolepis microstoma for 130 or 265 days showed modifications in phosphorus-containing metabolite ratios when compared to those of normal liver. After 130 days of infection the metabolite ratio of inorganic phosphate (Pi)/beta ATP significantly increased whereas that of phosphocreatine (PCr)/beta ATP significantly decreased. In older, 265 day infections, the increase in Pi/beta ATP and decrease in PCr/beta ATP persisted. Changes in the group infected for 130 days were accompanied by lowered pH. Analysis of liver extracts from mice with 130-day-old. H. microstoma revealed significantly lower concentrations of Pi, ATP and ADP compounds. In those from mice infected for 265 days the concentration of Pi remained low whereas concentrations of ATP and ADP increased to levels in between those of controls and the 130-day-old infection. In addition, levels of phosphorylethanolamine (PE) and of an unknown metabolite significantly increased in this latter group. Worm extracts contained high levels of glycerophosphorylcholine (GPC), Pi, fructose 1,6-diphosphate (FDP), PE, diphosphodiesters (DPDE), phosphorylcholine (PC) and glycerolphosphorylethanolamine (GPE) in order of declining concentrations, respectively. PMID- 8468142 TI - [The quality of the basic cause of death in the Statistical Bulletin of Mortality. Spain, 1985]. PMID- 8468143 TI - [Intravenous drug addiction and the risk of HIV infection in Madrid in 1990]. AB - As part of a multicenter WHO study on HIV infection among drug injectors, 472 intravenous drug users (IDUs) were interviewed, 240 recruited in the streets and 232 at drug treatment centers. The objectives of the study were to assess the prevalence of HIV infection among IDUs of Madrid, to identify factors associated with risk reduction behaviors, such as the use of sterile syringes and condoms. Chi-square and logistic regression were used to test for differences and to estimate odds ratios. Prevalence of HIV infection among IDUs in Madrid was 50% (53% among those recruited in the street and 38% among those recruited at treatment centers). Forty five per cent of those interviewed were still sharing syringes. Out of the 315 sexually active subjects, only 22% reported using condoms always or almost always. These results suggest that a range of interventions should be implemented to promote change towards healthier behaviors, including syringe-exchange programs, methadone maintenance treatments and pre- and post-test counseling in those agencies which care for this population. PMID- 8468145 TI - [Barriers to verbal communication and consumer satisfaction with consultations in general medicine]. AB - With the objective of knowing the barriers to verbal communication experienced by general practice users, and their satisfaction with the information received, a sample of 1553 adults (> 14 years old), users of the Basque Health Service general practice services, was interviewed. A questionnaire of 13 questions, administered after the consultation, was employed. The most frequently experienced barrier was the lack of written information, that affected to a 77.7% of those interviewed. This percentage is greater (p < 0.005) among those visiting traditional doctors (81.9%), than among those enrolled with primary care teams (72.4%) or rural doctors (70.0%). Those who were given written information left out the consultation more satisfied than the others (p < 0.001). The provision of written information seems to be related to the user's satisfaction. It is advised to modify the doctors' attitude towards the communicative process with their patients. PMID- 8468144 TI - [Inequalities in health: perinatal and infant mortality in Spain]. AB - The interregional variation coefficient (VC) has been considered as an accurate measure of the dispersion of regional infant, neonatal, postneonatal and perinatal mortality rates. Thus, trends of annual VC have been analyzed, for each rate, from 1940 to 1986, to identify the evolution in time of the regional differences with respect to these mortality rates. None of the four mortality rates showed a decreasing trend in their respective VCs. This may indicate that interregional differences do not change along time. The postneonatal mortality rate has been shown to have the highest VCs during the study period (ranging from 23 to 40%), with an independent evolution with respect to neonatal mortality rate, probably because the factors that influence both rates are clearly different. PMID- 8468146 TI - [Consumer satisfaction with 2 models of primary care in operation in Andalucia]. AB - A study was completed to investigate if any differences are observed in user satisfaction with health care centres, polyclinics and solo-practice, furthermore to identify user, organizational characteristics and doctors as variables that relate to user satisfaction in health care. A sample of users was chosen from the Andalusian cities of Granada, Malaga and Sevilla with an alpha = 5%, beta = 10% and d = 11%. The variables were collected trough the use of three questionnaires. Greater satisfaction was found between health care centre users than with polyclinics and solo-practice, with values being 62.4, 58.2 and 60.6 with a p < 0.001. The variables more strongly associated with user satisfaction in health care centres are those related with doctors and organization characteristics. Therefore several are capable of improvement in order to increase user satisfaction. On the contrary in polyclinics and solo-practice the most influential variables are those related with the user characteristics, which are not modifiable by the health services intervention. PMID- 8468147 TI - Controlling the HIV epidemic among drug injectors. PMID- 8468148 TI - Attitudes toward primary care are changing. PMID- 8468149 TI - UI hospitals touches every part of Iowa. PMID- 8468150 TI - Understanding the problems of the elderly. PMID- 8468151 TI - Training for Iowa physicians. PMID- 8468152 TI - UI researches environmental health risks. PMID- 8468153 TI - Cocaine abuse in a high risk obstetrical population. PMID- 8468155 TI - National Scientific Medical Meeting. The Royal College of Physicians of Ireland. 18-20 March 1993. Abstracts. PMID- 8468154 TI - Hospital ethics committees. PMID- 8468156 TI - Properties of the purified elongation factor 2 in the thermoacidophilic archaebacterium Sulfolobus solfataricus. AB - The elongation factor 2 (aEF-2) has been purified to homogeneity from the extreme thermoacidophilic archaebacterium Sulfolobus solfataricus. It is the only target protein which is ADP-ribosylated by diphtheria toxin in presence of NAD and this modification abolishes its property to support poly(Phe) synthesis in vitro. The factor is constituted by a single polypeptide chain with a relative molecular mass of 78,000 and an isoelectric point of 5.9. aEF-2 is resistant to heat denaturation as shown by the fact that its capability to be ADP-ribosylated was only 10% reduced after 4 h treatment at 80 degrees C. Its amino acid composition does not reveal significant differences with that of analogous factors in other sources; nevertheless, the deviation function indicates that aEF-2 is related to Sulfolobus acidocaldarius and eukaryotes EF-2 more than to eubacterial EF-G or other archaebacterial EF-2. PMID- 8468157 TI - Different outcomes of pregnancy in women with essential thrombocytosis. PMID- 8468158 TI - A new design of pyloromyotom for pyloromyotomy in infants--a modification of the Benson spreader. PMID- 8468159 TI - Urine osmolality in nursery school children in a hot climate. PMID- 8468160 TI - Helicobacter pylori and peptic ulcer disease. PMID- 8468161 TI - The importance of drinking. PMID- 8468162 TI - The role of high-dose chemotherapy with autologous bone marrow support in breast cancer: state of the art. PMID- 8468163 TI - Janusz Korczak. PMID- 8468164 TI - Paracetamol overdosage in Jerusalem 1984-89". PMID- 8468165 TI - Sixth autoimmunity meeting--Georg Wick day. 23 March 1992, Tel-Hashomer, Israel. Proceedings. PMID- 8468166 TI - Altered immunoendocrine dialogue in autoimmune disease. AB - Autoimmune diseases have a multifactorial pathogenesis including essential genetic and nonessential modulatory factors. Among the essential factors, not only should genes coding for an abnormal reactivity of the immune system be considered, but we have, in addition, provided experimental evidence for the existence of genes responsible for a susceptibility of the target organ/structure for the autoimmune attack. Only when both sets of essential genes are present does an autoimmune disease develop at all. The modulatory factors then determine the final outcome in each case. The present contribution discusses the immunomodulating role of glucocorticoid and sex steroids focussing on the Obese Strain (OS) of chickens, a model for Hashimoto thyroiditis. PMID- 8468167 TI - Pathogenic natural autoantibodies. PMID- 8468168 TI - Immune response genes and autoimmune diseases. PMID- 8468169 TI - Human CD5+ B cells and autoimmunity. PMID- 8468170 TI - Immunotherapeutic approach to rheumatoid arthritis with anti-idiotypic antibodies to HLA-DR4. PMID- 8468171 TI - Cytokines, interleukin-3 and autoimmunity. PMID- 8468172 TI - Analysis of the T cell receptor V gene usage in multiple sclerosis and human autoimmune thyroiditis. PMID- 8468173 TI - Do natural autoantibodies play a role in physiologic red blood cell sequestration? PMID- 8468174 TI - The use of ultrasound in children with pain around the hip and thigh. AB - The use of ultrasound in the evaluation of effusion of the hip is well established. We performed ultrasound examinations on 87 children who presented with a limp and with pain in the hip region. We confirm the diagnostic value of ultrasound in detecting an effusion in the hip. Furthermore, ultrasound examination revealed effusion in two cases (psoas myositis), an unexpected effusion in the contralateral hip in two cases, and the cause of the pain in eight cases without effusion. PMID- 8468175 TI - Assessment of uterine and umbilical artery velocimetry during latent and active phases of normal labor. AB - Twenty healthy parturients in active labor were monitored with continuous wave Doppler to assess changes in uterine and umbilical velocity waveforms. Each case served as its own control. Tracings of fetal heart rate monitoring were normal in all patients. The analysis of the waveforms included the peak systolic/end diastolic ratio for the umbilical circulation (umbilical artery), and the systolic minus diastolic velocity divided by systolic velocity (resistance index) was used as an indication of downstream resistance in the uterine arteries. Recordings from umbilical, left and right uterine arteries were obtained during various stages of progression of labor as indicated by Friedman's curve. In latent phase labor with intact membranes, as well as in three consecutive measurements throughout active phase labor until delivery, umbilical artery systolic/end-diastolic ratios, before, during and after contraction did not change--2.2 +/- 0.5, 2.3 +/- 0.6, 2.2 +/- 0.3 and 2.5 +/- 0.7 (NS). No changes in the resistance to flow in the left and right uterine arteries were recorded during both latent and active phases of labor--0.53 +/- 0.09, 0.52 +/- 0.1, 0.5 +/- 0.07, 0.56 +/- 0.07 (NS) and 0.59 +/- 0.1, 0.57 +/- 0.1, 0.56 +/- 0.1, 0.59 +/- 0.08 (NS), respectively. These results suggest stability of the fetal cardiovascular system ensuring continuous constant gas exchange process during labor, enabling most term fetuses to tolerate labor to a degree where minimal if any metabolic changes occur. PMID- 8468176 TI - Early severe dehydration in young breast-fed newborn infants. AB - Six breast-fed infants living in a dry desert climate area presented at ages 4-11 days with severe dehydration. In all cases, dehydration was associated with inadequate breast milk production by the mothers. In contrast to earlier reports on dehydration in breast-fed infants, five of the mothers were from a low socioeconomic background and three were multiparas, including two mothers who had previous experience with breast-feeding. In two infants severe bacterial infections were documented. Two mothers had small retracted nipples. As in earlier reported instances, sodium concentration in breast milk was elevated in all five mothers in whom it was measured, and three babies had severe hypernatremia. Successful relactation was achieved in three cases with a decrease in the milk sodium concentration. These data demonstrate that severe dehydration in breast-fed infants may occur as early as the first week of life and may affect even infants of experienced multiparous mothers who are well motivated for breast feeding. It seems that hypernatremia in these infants is secondary to poor fluid intake and increased insensible water loss rather than to elevated milk sodium, since there was no direct correlation between milk sodium concentration and serum sodium levels. Following fluid resuscitation, relactation can be achieved in motivated mothers. PMID- 8468177 TI - A centralized intravenous additive system in an Israeli government hospital. AB - The pharmacy of the Barzilai Medical Center initiated a centralized method for preparation of the sterile i.v. antibiotic dilutions used in the hospital that has proven to be beneficial to the patient and cost-effective to the hospital. With this system, all small-volume bags containing antibiotic dilutions- constituting 58.5% of all the sterile dilutions used in the Medical Center--are prepared centrally in the pharmacy of the hospital rather than in the various wards. Since the method requires professional supervision, it leads to an improvement in the quality of patient care. The solutions are prepared under sterile conditions, and care is taken to ensure their stability as well as to prevent incompatibilities between the antibiotics and the diluents. In addition to the direct benefit to the patient there has been a saving of approximately NIS 200,000/year resulting from the decrease in the number of minibags, syringes and needles, personnel time and wastage. PMID- 8468178 TI - 14C-urea breath test--a simple, noninvasive method for the detection of Helicobacter pylori infection. PMID- 8468179 TI - The relationship between estrogen/progesterone ratio and term human parturition. PMID- 8468180 TI - Pulmonary balloon dilation for valvular and arterial stenosis. AB - The use of balloon catheters to dilate obstructed vascular lesions represents one of the major advances in cardiology and dates back to 1964 when Dotter and Judkins reported their experience in dilating arteriosclerotic obstructive lesions. Since that time, the technique of balloon dilation has been used extensively for coronary and peripheral vascular lesions but also has been applied to such diverse cardiac lesions as pulmonic stenosis, mitral stenosis, aortic stenosis, aortic coarctation, superior vena caval and pulmonary venous obstructions. Balloon dilation has been used for both valvular and arterial pulmonary stenosis. The purpose of this study is to report on our initial experience in Hawaii with balloon dilation of valvular pulmonic stenosis and also with dilation of peripheral pulmonary artery stenosis due to congenital causes and as a residual postoperative lesion. PMID- 8468181 TI - Quality improvement: how does it differ from quality assurance? AB - Quality improvement? How does it differ from Quality assurance? The "Total Quality Management" movement which has been so successful in improving the quality of manufactured products in Japan and more recently in the United States has arrived in American service industries, including health care. Although a minority of health care institutions has adopted the Continuous Quality Improvement (CQI) or Total Quality Management (TQM) philosophy and techniques on their own, the new Joint Commission on Accreditation of Health Care Organizations (JCAHO) standards to be phased in over the next 3 years require all accredited hospitals to "adopt the new philosophy". PMID- 8468182 TI - Vaginal birth after cesarean section in Hawaii. Experience at Kapiolani Medical Center for Women and Children. AB - Medical records at Kapiolani Medical Center for Women and Children were reviewed for cases that had a trial of labor subsequent to prior cesarean section during the period January 1990 to July 1991. All cases were > or = delivered 36 weeks' gestation. During the 19-month period, 356/483 or 73.5% cases with a trial of labor had successful vaginal births after previous cesarean sections (VBAC). The majority of the others that did not were due to failure of progression in labor. The incidence of scar separation was 5/483 (1.04%). There were 5/483 neonates with Apgar scores of < or = 6 at 5 minutes, giving a perinatal morbidity rate of 1.04%. There were no maternal deaths. Oxytocin induction resulted in successful VBAC in 30/47 (63.8%) cases. This study concludes that a trial of labor for vaginal birth after cesarean section is well established at our institution. In addition, the rates of successful VBAC, its complications and outcomes, are comparable to national averages. PMID- 8468183 TI - Cross-cultural dream use in Hawaii. AB - Cultural variations in the narrative content of dreams have been reported in many studies. This basic cultural difference in dream language and representations has been used to support psychoanalytic theories of dreaming, especially that of the Jungian-based schools. Others have postulated that such variations reflect the cultural differences that each individual experiences during waking life. This "continuity" hypothesis proposes that a high correlation exists between an individual's waking life and his or her dream content. The biologic framework of dreams, sleep/dream-state physiology, is cross-culturally consistent, and the incidence of dream related pathology also is remarkedly similar between differing cultures. PMID- 8468184 TI - Differentiation of silver-enhanced mercury and gold in tissue sections of rat dorsal root ganglia. AB - Autometallography was used in conjunction with light and electron microscopy to detect traces of gold and mercury in the dorsal root ganglia of rats treated with sodium aurothiomalate and mercuric chloride. In order to differentiate between gold and mercury in tissue sections, the gold accumulations were removed by potassium cyanide, leaving mercury sulphides/selenides as the only possible catalysts for autometallographic development. With this technique, it is now possible to differentiate between all tissue metals capable of initiating the autometallographic process, i.e. gold, vesicular zinc, and sulphides and selenides of mercury and silver. PMID- 8468185 TI - The effects of storage on the retention of enzyme activity in cryostat sections. A quantitative histochemical study on rat liver. AB - The effect of storage of unfixed cryostat sections from rat liver for 4 h, 24 h, 3 days and 7 days at -25 degrees C was studied on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, xanthine oxidoreductase, glutamate dehydrogenase, succinate dehydrogenase (all demonstrated with tetrazolium salt procedures), glucose-6-phosphatase (cerium-diaminobenzidine method), 5'-nucleotidase (lead salt method), dipeptidyl peptidase II, acid phosphatase (both simultaneous azo coupling methods), D-amino acid oxidase (cerium-diaminobenzidine-cobalt-hydrogen peroxide procedure) and catalase (diaminobenzidine method). The effect of drying of the cryostat sections at room temperature for 5 and 60 min was investigated as well. The enzyme activities were quantified by cytophotometric measurements of test and control reactions. The test minus control reaction was taken as a measure for specific enzyme activity. It was found that the activities of all the enzymes investigated, with one exception, were affected neither by storage of the cryostat sections at -25 degrees C for up to 7 days, nor by drying of the sections at room temperature for up to 60 min. The exception was xanthine oxidoreductase, whose activity was reduced by 20% after 5 min drying of sections or after 4 h storage. Therefore, only incubations for xanthine oxidoreductase activity have to be performed immediately after cutting cryostat sections, whereas for the other enzymes a considerable margin appears to exist. PMID- 8468186 TI - Immunohistochemical detection of strain-specific major histocompatibility complex class I antigens in paraffin-embedded rat osteochondral tissue. AB - An immunohistochemical method using formalin-fixed, paraffin wax-embedded sections is described for detecting strain-specific major histocompatibility complex class I antigens in knee-joint tissue from DA and Lewis strains of rat. The fixed osteochondral tissues were additionally decalcified in formic acid before processing for paraffin wax embedding. For immunohistochemistry, two monoclonal antibodies, one specific for DA class I allele RT1Aa and the other for Lewis class I allele RT1A1, were used together with the avidin-biotin immunoperoxidase procedure. It was necessary to use strain-specific normal rat serum as a diluent for the antibodies to suppress cross-strain recognition. DA specific antibody stained positively only on DA rat sections, not on Lewis rat sections, and Lewis-specific antibody stained positively only on Lewis rat sections, and not on DA. Positive staining was localized in the bone marrow, osteochondral cells and endothelium. We propose that the use of a decalcification medium may have enhanced the immunoreactivity of the tissue. The method described can be used on sections of allografts from the two strains of rat to assess morphologically the extent of cellular replacement of the graft by the host's cells. PMID- 8468187 TI - Fate of degenerating lactotrophs in rat pituitary gland after interruption of lactation: a histochemical and immunocytochemical study. AB - In the pituitary gland of pregnant and lactating rats a striking proliferation of lactotrophs occurs to meet the increased demands for prolactin. Following interruption of lactation the redundant lactotrophs undergo a massive degeneration until pre-pregnant proportions are re-established. Immunocytochemical detection of prolactin allows the recognition of degenerating lactotrophs until advanced stages of degeneration and leads to the conclusion that this process is autolytic in nature. Histochemistry of acid phosphatase reveals a remarkable accumulation of this enzyme in Golgi cisternae and lysosomes. At later stages of degeneration the acid phosphatase spreads throughout the entire cell. The presence of increased numbers of necrotic cells appears to activate phagocytosis of stellate cells and, to a lesser extent, of follicular cells. Stellate cells responsible for the secondary processing of cell residues are isolated cells characterized by a prominent oval nucleus and an electron-lucent cytoplasm with scarce organelles and extensive cytoplasmic processes. They appear as scavenger cells engulfing cell remnants and debris. Immunocytochemistry of S-100 protein discloses differential staining of two types of cell, one forming clusters of 2-4 cells with faint immunoreactivity, while the other type consists of isolated cells with a stellate profile and stronger labelling to S-100 protein. PMID- 8468188 TI - A monoclonal antibody distinguishes growth cartilage from other types of cartilage: a new probe for osteogenic cartilage. AB - Monoclonal antibodies (mAbs) were raised by injection of a homogenate of cultured growth cartilage (GC) cells from young rabbit ribs. These mAbs were examined by immunohistochemical staining for their reactivity to paraffin sections of rabbit tissues. The results showed that an mAb reacted preferentially with late hypertrophic and calcified costal GC zones. The mAb also reacted with hypertrophic GC adjacent to bone that existed in sternum and femur, but not to other cartilages, including resting cartilage, articular cartilage, auricular cartilage, nasal cartilage, tracheal cartilage and meniscus cartilage, or with other tissues, including tendon, skin, muscles, lung, liver, heart, thymus, spleen, eye and gut. It reacted with a wider area of the GC zone when the sections were decalcified, although its reactivity with the extended area was much less intensive than that with late hypertrophic and calcified GC zones. On treatment of the sections with bacterial collagenase, neither the reactive area nor its intensity were changed, while when treated with trypsin the reactivity was lost. These results suggest the existence of a certain molecule which distinguishes GC (osteogenic cartilage) from other (non-osteogenic) cartilage. This mAb is a useful probe for distinguishing osteogenic cartilage from non osteogenic cartilage, and for studying differentiation steps of cartilage cells in endochondral bone formation. The mAb can also be used as a probe for clinical and stored specimens because it reacts with decalcified and paraffin-embedded human specimens. PMID- 8468189 TI - Histochemistry of carbohydrates as performed by physical development procedures. AB - The histochemistry of carbohydrates demonstrated by means of physical development procedures has been reviewed in terms of the use and reliability of the procedures, physical developers, practice of the procedures, a fundamental series of light and electron microscopic methods and certain other promising aspects of this area of histochemistry. A line of fundamental light- and electron microscopic histochemical methods for carbohydrates using physical development procedures such as periodic acid-thiocarbohydrazide-silver protein-physical development (PA-TCH-SP-PD), high- or low-iron diamine (HID or LID)-TCH-SP-PD and lectin-gold (LT-G)-PD and related methods has been found to be more efficient, compared with those without physical development procedures. Since a series of other promising histochemical methods for carbohydrates using physical development procedures have been derived or are now being introduced, these procedures could be regarded as an unusually potent vehicle for effectively advancing carbohydrate histochemistry in both light and electron microscopy. PMID- 8468191 TI - Molecular heterogeneity of the actin filament cytoskeleton associated with microvilli of photoreceptors, Muller's glial cells and pigment epithelial cells of the retina. AB - The present study addressed the question as to whether the four different actin associated proteins that are associated with the actin core bundle in intestinal microvilli (i.e. villin, fimbrin, myosin I and ezrin) are essential components of all microvilli of the body. The retina provides an excellent example of a tissue supplied with three different sets of microvilli, namely those of Muller's glial cells (Muller baskets), photoreceptors (calycal processes), and pigment epithelial cells. The main outcome of this study is that none of these microvilli contain all four actin-associated proteins present in intestinal microvilli. Muller cell microvilli contain villin, ezrin and myosin I (95 kDa isoform) but not fimbrin. Calycal processes of photoreceptors contain fimbrin but not villin, myosin I and ezrin. Finally, microvilli of pigment epithelial cells are positive for ezrin but not for villin, fimbrin and myosin I. Because of limited cross reactivities of the antibodies to myosin I and ezrin, the myosin I data refer to the chicken retina whereas the findings with anti-ezrin were obtained with the rat retina. A further outcome of this study is that the actin filament core bundles in microvilli of chicken pigment epithelial cells are presumed to contain a crosslinking protein, which is not immunologically related to either villin, fimbrin or myosin I of the intestinal brush border. PMID- 8468190 TI - The versatility of microvascular pericytes: from mesenchyme to smooth muscle? PMID- 8468192 TI - Carbonic anhydrase isoenzymes II and I are present in the zona glomerulosa cells of the human adrenal gland. AB - Human carbonic anhydrase isoenzymes I and II (HCA I and II) were purified from human erythrocytes by inhibitor affinity chromatography and ion-exchange chromatography. These isoenzymes were then located in the human adrenal gland using specific polyclonal antisera raised in rabbits and specific detection by immunohistochemical techniques. Both HCA II and I were located in the zona glomerulosa cells, although the staining for HCA I was faint. The cells of the zona fasciculata and the zona reticularis failed to stain with either antiserum. Control stainings with preimmune or anti-HCA VI sera were negative. The presence of HCA II and I in the zona glomerulosa cells may be linked to regulation of the biosynthesis or secretion of mineralocorticoids. PMID- 8468193 TI - Quantitative X-ray microanalysis of adrenal medullary cells of young adult and aged rats after glutaraldehyde fixation and potassium dichromate treatment. AB - X-ray microanalysis has been used to detect chromium in the histochemical reaction product resulting from the reaction of noradrenaline with glutaraldehyde during fixation of the rat adrenal medulla and subsequent treatment with potassium dichromate. In unstained ultrathin sections, noradrenaline cells can be identified by their content of highly electron-dense storage granules, which enables individual granules to be analysed quantitatively to assess the amount of bound chromium within them. In young adult (4-month-old) rats the mean chromium content of noradrenaline-containing adrenal medullary granules was 443.6 +/- 50.7 mM/kg dry weight. In aged (24-month-old) animals the mean chromium content was 267.0 +/- 64.0 mM/kg dry weight which was significantly (P < 0.01) lower then the value for the young adult rats. Some noradrenaline cells contained granule populations, which were markedly less electron dense than those in the young adults and this is reflected in the ranges of chromium values recorded between individual cells in the 24-month-old animals. There were also noradrenaline cells in the medulla of the aged animals, which contained highly electron-dense granules but these did not contain as much bound chromium as the highest values recorded in the young adult animals. The results are discussed in the context of the growth of the rat adrenal medulla throughout the lifespan and with respect to the effects of age on the integrity of storage granules. PMID- 8468194 TI - Gamma-aminobutyric acid-immunoreactive neurons in the rat trigeminal nuclei. AB - The distribution of GABAergic neurons in the rat trigeminal nuclei was studied using a highly specific monoclonal antibody (mAb3A12) to gamma-aminobutyric acid (GABA). Immunopositive cells were relatively abundant in the marginal and gelatinosa beds of the caudal part of the trigeminal spinal tract nucleus, and in the dorsomedial areas of the oral subnucleus and the principal nucleus. A high density of GABA-immunoreactive somata was also found in the rostral part of the oral subnucleus and in the adjacent parvicellular reticular formation as well as in the supratrigeminal and intertrigeminal regions. Thus, the distribution of the GABAergic cells showed a relatively high density in areas related to the convergence of sensory stimuli, and in zones that contain interneurons inhibiting masticatory motoneurons. The results suggest, therefore, that GABA might play an important role both in discriminative sensory processing and in reflex modulation of the orofacial region. PMID- 8468195 TI - Simultaneous histochemical demonstration of capillaries and muscle fibre types. AB - Immunohistochemical staining of fibronectin is proposed as a good method for demonstrating capillaries in skeletal muscle tissue. The reaction superimposed on the histochemical reaction for myofibrillar ATPase enables simultaneous demonstration of fibre typing and capillary supply on the same tissue section. The method is quick and makes possible automated image analysis. PMID- 8468196 TI - Flat bed scanner in the quantitative assay of 35SO4-incorporation by X-ray film autoradiography of intervertebral disc sections. AB - A rapid quantitation of proteoglycan synthesis distribution in intervertebral disc and endplates is described. Tissue blocks of disc (C7-Th1) in the midsagittal plane from ten female beagles were incubated in the presence of 35SO4 and prepared as histological slides. For comparison, sulphate incorporation rates in the C5-C6 discs were assayed by liquid scintillation. Autoradiographic film exposed against the labelled sections was developed and digitized for image analysis using a 256 grey level flat bed table scanner connected to a microcomputer. The film density versus dpm (disintegrations per minute) calibration was performed using a set of 35SO4-labelled glycosaminoglycan standards applied on the same film. Since section thickness, dpm calibration of the film density and the specific activity of sulphate in the medium were known, the incorporations per tissue volume could be calculated. The average incorporation rates of the anterior and posterior annulus fibrosus, nucleus pulposus and vertebral endplates were 5.2 +/- 0.9, 5.2 +/- 0.8, 4.5 +/- 0.6 and 4.1 +/- 0.8 pmol/mm3 per h (+/- SE, n = 10), respectively and closely corresponded to those obtained by liquid scintillation. This method offers a convenient and reproducible way to measure the rate of proteoglycan synthesis in large tissue sections but also in thin cartilaginous tissues such as the vertebral endplate. PMID- 8468197 TI - The use of sodium sulphide-fixed brain tissue for immunocytochemical staining of activated microglia and reactive astrocytes. AB - The use of sodium sulphide-perfused material for the immunocytochemical demonstration of microglia and astrocytes is described. An intracerebroventricular injection of kainic acid (KA) was used to induce neuronal degeneration and subsequent axonal sprouting in the hippocampus. Animals under deep anaesthesia were killed by perfusion with either 4% paraformaldehyde alone or with 1% sodium sulphide followed by 4% paraformaldehyde solution. Microglial cells were identified with OX-42, a monoclonal antibody towards CR3 complement receptors, and astrocytes with a polyclonal antibody to glial fibrillary acidic protein (GFAP). The present study reveals a marked enhancement in the immunoreactivity of activated microglial cells in sodium sulphide perfused tissues compared to those observed in tissues fixed in paraformaldehyde alone. GFAP immunoreactivity of the astrocytes was not compromised by the use of sodium sulphide. The results clearly show the suitability of sodium sulphide perfused tissues for immunocytochemical procedures and should provide a useful tool for investigation of the role of neuroglial cells in axonal sprouting. PMID- 8468199 TI - Comments on withdrawal of penicillin/streptomycin combinations. PMID- 8468198 TI - Galactose-binding lectins as markers of pregnancy-related glycoproteins. AB - Protein extracts from pregnant mouse endometria were compared with those obtained from non-pregnant and pseudopregnant mice to detect early pregnancy-specific galactose-rich glycoproteins. Gradient gel electrophoresis combined with lectin overlay and lectin histochemistry were used to identify Ricinus communis I (RCA I), R. communis II (RCA-II) and Cytisus scoparius (CSA) lectin binding glycoproteins. Using this approach, galactose-rich glycoproteins were identified that were maximally expressed in the estrus phase of non-pregnant endometria and also those that had peak expression in pregnancy. Lectin histochemistry revealed pregnancy related changes in three portions of mouse endometrium: endometrial glands, luminal epithelium and its basement membrane. Two major glycoproteins (RCA-I reactive 64 kDa and RCA-II reactive 35 kDa) were specifically expressed in peri-implantation endometrium on days 3 and 4 of pregnancy. The appearance of these glycoproteins during the period of the implantation window in mouse suggests that they could serve as markers of uterine receptivity to the implanting blastocyst. PMID- 8468200 TI - Women in leadership roles. PMID- 8468201 TI - Viewpoints on borreliosis. PMID- 8468202 TI - Concern for all immunosuppressed clients. PMID- 8468203 TI - "Spay or pay"--is mandatory sterilization the answer to pet overpopulation problem? PMID- 8468204 TI - 1991 US veterinary practice revenue and expenses. PMID- 8468205 TI - An idea whose time has come: veterinarians in humane society administration. PMID- 8468206 TI - Survey of state veterinarians and state veterinary diagnostic laboratories for selenium deficiency and toxicosis in animals. AB - Surveys were performed in which the state veterinarian and the major state veterinary diagnostic laboratories in every state were asked about selenium (Se) deficiency and toxicosis in livestock and wildlife in their state. Selenium deficiency diseases were diagnosed in 46 states and were reported to be an important livestock problem in regions of 37 states; deficiencies were diagnosed in wildlife in 10 states. Natural Se toxicosis was a rare problem, with only 7 states reporting naturally developing Se toxicosis. Oversupplementation with Se was reported as a cause of toxicosis in 15 states. Toxicoses in aquatic environments were reported from 4 states; in all cases, high-Se content in the water had resulted from agricultural irrigation or natural rainfall causing leaching of Se from high-Se soils. Current amounts of supplemental Se that can be fed to our major food-producing animals are being reviewed by the FDA because of speculation of potential environmental problems caused by Se supplementation in animals. Amounts of supplemental Se allowed in the western United States (states west of and including North Dakota, South Dakota, Nebraska, Kansas, Oklahoma, and Texas) are proposed by the FDA to have more potential for environmental Se enrichment and toxicosis. This premise was not supported by our data. Selenium supplementation in domestic livestock was not involved in wildlife toxicosis found by these surveys. PMID- 8468207 TI - Difficult dermatologic diagnosis. PMID- 8468208 TI - Randomized field trial to determine the effects of oral selenium supplementation on milk production and reproductive performance of Holstein heifers. AB - A field trial was conducted to measure differences in performance between selenium-supplemented and nonsupplemented heifers on a 1,200-cow California dairy. One hundred seventeen 19- to 27-month-old Holstein heifers were randomly assigned to treatment (n = 59) and control (n = 58) groups. A federally approved, commercially available, sustained-release intraruminal selenium bolus was administered to each heifer in the treatment group. Blood samples were taken from treated and control animals to assess selenium values before and after bolus administration and again after introduction to the milking ration. Production data were obtained from an on-farm computerized record system for each heifer during her first lactation. Mean blood selenium concentrations in treated heifers were higher than those in control heifers from posttreatment day 30 until after calving. Data analyzed in midlactation and late lactation indicated no significant differences between treated and control groups in somatic cell count, days not pregnant, total milk produced, or times bred. PMID- 8468209 TI - The gentle cow as scapegoat for world hunger? PMID- 8468210 TI - The human side of veterinary medicine. The tough job of talking about risk. PMID- 8468211 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. New developments in small animal population control. PMID- 8468212 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. One generation away from humanity. PMID- 8468213 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. Working with breeders on solutions to pet overpopulation. PMID- 8468214 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. Early-age neutering of dogs and cats. PMID- 8468215 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. Veterinary practitioners' role in pet overpopulation. PMID- 8468216 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. The pet owner and breeder's perspective on overpopulation. PMID- 8468217 TI - Animal welfare forum: overpopulation of unwanted dogs and cats. Role of breeding regulation laws in solving the dog and cat overpopulation problem. PMID- 8468218 TI - Genetic study of hyperkalemic periodic paralysis in horses. AB - Four Quarter Horses (1 stallion, 3 mares) with hyperkalemic periodic paralysis were mated to unaffected horses to determine the genetic basis of the disease. The affected stallion was bred to 11 unaffected mares (4 Quarter Horses, 1 Arabian, 2 Standardbreds, and 4 Thoroughbreds). The 3 affected mares were bred to an unaffected Quarter Horse stallion. Of the 15 offspring obtained from these matings, 9 were affected with hyperkalemic periodic paralysis, and 6 were unaffected, consistent with an autosomal dominant mode of inheritance. Diagnosis was established by results of oral administration of potassium chloride and demonstration of characteristic clinical signs accompanied by hyperkalemia. Oral administration of potassium chloride resulted in marked increases in plasma potassium concentrations in affected and unaffected foals, although hyperkalemia was associated with clinical signs of hyperkalemic periodic paralysis in the affected foals. Evaluation of blood samples from affected and unaffected offspring revealed no linkage with erythrocyte and serum markers at 24 loci. PMID- 8468220 TI - Vaporizer in circle for delivery of isoflurane to dogs. AB - An in-circuit vaporizer for delivery of isoflurane was evaluated. The isoflurane concentration within an isolated circle breathing circuit was determined for 1 hour in 6 in-the-circuit vaporizers with the wicks removed. A mechanical ventilator and artificial lung were connected to the circuit. Isoflurane concentration increased as vaporizer setting increased, and delivered concentration (%) at 60 minutes (mean +/- SEM) ranged from 0.46 +/- 0.10 at tap setting 1 to 3.67 +/- 0.30 at setting 5. Temperature of the isoflurane did not change. Cardiovascular and respiratory function were maintained within a clinically acceptable range in 6 dogs anesthetized with thiamylal and maintained with 1.87% end-tidal isoflurane delivered from the in-circuit vaporizer during spontaneous ventilation, controlled ventilation, and closed-circuit anesthesia. The range of vaporizer tap settings (mean +/- SEM) was lower during closed-system anesthesia (2.5 +/- 0.1 to 3.5 +/- 0.6) and during controlled ventilation (2.6 +/ 0.2 to 3.3 +/- 0.2) than during semi-closed system anesthesia (5.4 +/- 0.3 to 6.8 +/- 0.4). The in-circuit vaporizer was used to deliver isoflurane to 36 dogs anesthetized for a variety of surgical and medical procedures. Ventilation was spontaneous, assisted, and in 1 instance, controlled. Cardiovascular function, respiratory function, and recovery times were within clinically acceptable ranges. The initial vaporizer tap setting (mean +/- SEM) was 8.2 +/- 0.4, and this corresponded to an end-tidal isoflurane concentration of 3.5 +/- 0.6. The range of vaporizer settings during the maintenance phase (mean +/- SEM) was 2.8 +/- 0.5 to 4.6 +/- 1.9.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468219 TI - Within-herd and between-herd variation in diagnosis of clinical mastitis in cattle. AB - In a set of data on farmer-observed clinical mastitis in cattle, all milk samples were scored with regard to milk color and milk texture (presence of flakes and viscosity). During a 1-year period, 1,106 milk samples were collected from 125 farms with a bulk milk somatic cell count < 150,000 cells/ml. The overall variation, the between-herd variation, and the within-herd variation of the scores were evaluated and compared with each other. Differences between farmers were found for the scores on the visual characteristics per sample. However, these differences were not related to the reported number of cases of clinical mastitis per year. It was concluded that the diagnostic capability of farmers whose herds had low somatic cell counts did not have a negative influence on the validity of farmer-observed clinical mastitis incidence. However, care should be taken in herds with a low frequency of cases. PMID- 8468221 TI - Effect of total ablation of the external acoustic meatus and bulla osteotomy on auditory function in dogs. AB - Seven dogs with end-stage bilateral otitis externa were evaluated for auditory function before and after bilateral total ear canal ablation and lateral bulla osteotomy. Evaluations were performed by owner questionnaire and by recording brainstem auditory-evoked responses. Prior to surgery, all dogs could hear a loud voice or noise, however, only 3 dogs responded to a voice spoken at a normal level. Of the 14 ears tested electrodiagnostically, only 1 did not have a response, using air-conducted or bone-conducted stimuli. After surgery, 2 dogs responded to a normal voice, but all 7 responded to loud voices or noise. Three ears that had recordable brainstem auditory-evoked responses to air-conducted stimulation prior to surgery, failed to respond after surgery. Ears that responded to bone-conducted stimulation prior to surgery also responded after surgery. PMID- 8468223 TI - Use of metyrapone to treat pituitary-dependent hyperadrenocorticism in a cat with large cutaneous wounds. AB - Metyrapone, a drug that inhibits cortisol production, was used to lower plasma cortisol concentration and alleviate skin lesions caused by pituitary-dependent hyper-adrenocorticism in a cat. Plasma cortisol concentration was documented by ACTH stimulation test results. During metyrapone treatment, alopecia, thin skin, and large cutaneous wounds resolved. Metyrapone was administered orally at a dosage of 65 mg/kg of body weight, every 12 hours. Metyrapone may be used in conjunction with surgery in the management of pituitary-dependent hyperadrenocorticism in cats. PMID- 8468222 TI - Salmonella choleraesuis pneumonia in a cat without signs of gastrointestinal tract disease. AB - Primary Salmonella choleraesuis pneumonia without enteric manifestations was diagnosed in an 8-year-old cat. The diagnosis was based on culture of the organism from bronchial brushings. Pathogens were not isolated from multiple fecal samples. The cat initially responded to treatment with sulfamethoxazole trimethoprim, but relapsed after the owner discontinued treatment because of difficulty in administration. Treatment with ampicillin, followed by amoxicillin, resulted in complete resolution of all pulmonary infiltrates. Possible mechanisms of Salmonella infection in this cat included nosocomial infection from a nonclinical carrier, as well as Salmonella bacteremia initiated during a dental procedure performed prior to the onset of clinical signs of pneumonia. PMID- 8468224 TI - Severe cardiomegaly secondary to anemia in a kitten. AB - Severe anemia in a weanling kitten resulted in volume overload hypertrophy of the heart and signs of congestive heart failure. A 6-week-old moribund kitten was admitted to the hospital with a PCV of 3%. The anemia was determined to have resulted from severe flea infestation and iron deficiency. Supportive therapy consisted of flea removal, blood transfusions, and oral nutritional support. On day 3 of hospitalization, the kitten had signs of depression and became tachypneic. Auscultation revealed a systolic murmur, gallop rhythm, and crackles over the ventral lung fields. Thoracic radiography revealed pulmonary edema and massive cardiomegaly. Echocardiographic evaluation revealed dilatation of all cardiac chambers. The addition of furosemide to the kitten's treatment protocol resulted in resolution of the pulmonary edema. On follow-up examination 1 month later, the kitten had mild residual cardiomegaly and the anemia had resolved. Anemia is a well-known sequela to severe flea infestation in young animals. A less commonly reported, but potentially life-threatening, sequela to anemia may include the development of volume overload hypertrophy of the heart and congestive heart failure. PMID- 8468225 TI - Acquired arteriovenous fistula secondary to castration in a dog. AB - A 6-year-old castrated male Basset Hound was examined because of a 1-year history of a pulsating mass in the right inguinal region. The pulsatile mass was diagnosed as an arteriovenous fistula by physical examination and angiography. Surgical exploration revealed that the right testicular artery and vein, the artery of the ductus deferens, and the cremasteric artery were involved in the fistula. The fistula was believed to have developed secondary to castration performed at 6 months of age. The mass and associated vessels were completely excised and signs of recurrence were not observed 13 months after surgery. PMID- 8468226 TI - Primary mesenchymal or mixed-cell-origin lung tumors in four dogs. AB - Primary lung tumors of mesenchymal or mixed cell origin were diagnosed in 4 dogs with clinical and radiographic abnormalities indicating an intrathoracic mass. Each dog had 1 large intrapulmonary lesion, and 1 dog also had nodules scattered throughout all lung lobes. Two dogs were euthanatized; 1 had a biphasic pulmonary blastoma; and the other had a pulmonary chondroblastic osteosarcoma with intrapulmonary metastases. The masses in the other 2 dogs were hamartomas (lipomatous in 1, microcystic in the other), which were resected. Both dogs survived more than 1 year after surgery. Primary lung tumors are uncommon in dogs and are generally malignant (adenocarcinomas or carcinomas). Tumors of connective tissue or mixed cell origin are rare, but the outcome is potentially good after surgical removal. PMID- 8468227 TI - Spiral colon intussusception in a three-year-old bull. AB - Intussusception of the spiral colon was diagnosed in a 3-year-old Charolais bull. Necropsy revealed the intussusception to involve approximately 40 cm of the first centripetal gyrus of the spiral loop, beginning 70 cm distal to the ileocolic junction. Predisposing lesions were not noticed in the mesentery or lumen of the affected intestine; however, the involved intestine was necrotic. Surgical resection of the lesion was not attempted because of the compromised nature of the involved large intestine and because of the inability to exteriorize the region in the standing animal. PMID- 8468228 TI - Intermittent antimicrobial infusion for management of a septic distal interphalangeal joint in a horse. AB - A 13-month-old Quarter Horse colt sustained a puncture wound to the frog region of the foot, which penetrated the navicular bursa and distal interphalangeal joint, 7 days prior to examination. A street-nail procedure was performed to debride the tract and provide drainage of the navicular bursa and distal interphalangeal joint. An indwelling lavage system was placed through the dorsal aspect of the joint and antimicrobials were infused intermittently to supply a high local concentration of drug and to frequently lavage the distal interphalangeal joint and navicular bursa. PMID- 8468229 TI - Echinocytosis in horses: 54 cases (1990). AB - Retrospective review of CBC and serum chemical data from 124 horses admitted to the veterinary teaching hospital over a 9-month period (Feb 1, 1990 to Oct 31, 1990) indicated that 54 horses had echinocytosis (prevalence = 44%). In horses with echinocytosis, the most frequent diagnosis was colitis (23 horses; 43%). Odds ratios (measure of association) were calculated to determine the association of echinocytosis with specific hematologic and biochemical abnormalities. When evaluated in a multivariate model, low serum sodium concentration (< 136 mEq/L) was the only variable significantly associated with the incidence of echinocytosis. Within the group of 54 horses with echinocytosis, hyponatremia (35 horses; 65%), hypochloremia (35 horses; 65%), low total carbon dioxide concentration (35 horses; 65%), hypoosmolality (30 horses; 55%), and hypocalcemia (22 horses; 41%) were the most common biochemical abnormalities. It was concluded that hyponatremia was associated with increased incidence of echinocytosis. It was suggested that systemic electrolyte depletion might be involved in the induction of echinocyte formation. PMID- 8468230 TI - Digit amputation in cattle: 85 cases (1971-1990). AB - Medical records of 83 cattle, which had 1 or more digit amputations performed at Kansas State University and The Ohio State University veterinary hospitals between 1971 and 1990, were reviewed. Signalment, duration of lameness, prior treatment, digit involved, and pathologic condition were evaluated. Owners were contacted with regard to the animal's duration in the herd after amputation and reason for exiting the herd, level of production attained, and degree of lameness. The animal was judged to have a good, fair, or poor recovery on the basis of this information. Septic arthritis of the distal interphalangeal joint and resulting complications were the problems most frequently treated by digit amputation. Fifty-one percent of cattle undergoing digit amputation attained preamputation production levels for a minimum of 24 months. Approximately 30% of cattle undergoing digit amputation were culled for lameness, usually within 7 months of surgery. Cattle remaining in the herd more than 12 months after amputation were unlikely to be culled for lameness, indicating that long-term breakdown of supporting structures was uncommon. Likelihood of a good recovery decreased from 71.4% in cattle weighing < or = 341 kg to 27.3% in cattle weighing > or = 682 kg. Cattle undergoing amputation of a rear medial digit were more likely to recover well than those undergoing amputation of either front digit. The most frequently performed amputation was that of a rear lateral digit, but it was associated with the poorest recovery, possibly because of the disproportionate amount of stress placed on this digit. Cattle used for dairy and beef production had approximately equal chances of a good recovery from digit amputation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468231 TI - Bordetella bronchiseptica pneumonia in a koala. AB - A 3-year-old male koala (Phascolarctos cinereus) was evaluated because of severe acute respiratory distress. Despite medical treatment, the koala died. Gross and histologic lesions consistent with acute bacterial pneumonia were identified at necropsy and Bordetella bronchiseptica was isolated from pulmonary tissue. There are 2 prior reports from Australia of fatal B bronchiseptica pneumonia in captive koalas. PMID- 8468232 TI - Immobilization and anesthesia of two hand-reared zebras. AB - This report describes our experiences with 2 drug combinations that were used safely and effectively to immobilize and anesthetize 2 hand-reared zebras. Zebras were sedated with xylazine hydrochloride or detomidine. The latter is more potent and of more use in healthy, vigorous animals. Anesthesia was induced with thiamylal/guaifenesin or tiletamine/zolazepam. The latter is more convenient because a quick, simple IV injection will preclude the necessity for physical restraint required to administer a large volume of guaifenesin/thiobarbiturate combination. Tracheal intubation was easily accomplished with either induction regimen, and inhalation anesthetic was used for longer periods of anesthesia. PMID- 8468233 TI - What is your diagnosis? Lysis of the left zygomatic process and the squamous portion of the left temporal bone. PMID- 8468234 TI - What is your diagnosis? Mass in the cranial mediastinum. PMID- 8468235 TI - Pepticinnamins, new farnesyl-protein transferase inhibitors produced by an actinomycete. I. Producing strain, fermentation, isolation and biological activity. AB - Pepticinnamins A, B, C, D, E and F, a family of farnesyl-protein transferase (FPT) inhibitors were isolated from the fermentation broth of Streptomyces sp. OH 4652. These inhibitors were purified from whole broth by extraction with chloroform, followed by silica gel column chromatography, Sephadex LH-20 chromatography and reverse phase HPLC. Among these, pepticinnamin C showed the most potent inhibition (IC50-100 nM). PMID- 8468236 TI - Pepticinnamins, new farnesyl-protein transferase inhibitors produced by an actinomycete. II. Structural elucidation of pepticinnamin E. AB - Structure of novel farnesyl transferase inhibitor, pepticinnamin E, is elucidated by NMR study. Pepticinnamin E is composed of five amino acids and o pentenylcinnamic acid, having a molecular weight of 907. C-terminal glycylserine of the compounds is in the cyclized diketopiperazine form. PMID- 8468237 TI - Novel antimycin antibiotics, urauchimycins A and B, produced by marine actinomycete. AB - Two novel antimycin antibiotics, urauchimycins A and B, were isolated from a fermentation broth of a Streptomyces sp. Ni-80. The strain was isolated from an unidentified sponge. Their chemical structures were determined by 2D NMR analysis. They are the first antimycin antibiotics which possess a branched side chain moiety. They exhibited inhibitory activity against morphological differentiation of Candida albicans. PMID- 8468238 TI - Mer-WF3010, a new member of the papulacandin family. I. Fermentation, isolation and characterization. AB - Mer-WF3010, a new member of the papulacandin family, was isolated from the mycelia of Phialophora cyclaminis Mer-WF3010 (FERM P-11475). The molecular formula of Mer-WF3010 was determined as C45H60O16. PMID- 8468239 TI - AB023, novel polyene antibiotics. I. Taxonomy of the producing organism, fermentation and antifungal activity. AB - AB023 is a complex of polyene antibiotics produced by an actinomycete, SD581, which was isolated from a Kenyan soil sample. The two main components, pentaene antibiotics AB023a and AB023b, have antifungal activity against some phytopathogenic fungi, particularly against Botrytis cinerea (MIC of 5 micrograms/ml). PMID- 8468240 TI - AB023, novel polyene antibiotics. II. Isolation and structure determination. AB - AB023, a complex of new polyene antibiotics, was isolated from a soil Streptomyces strain. The two main components, pentaene antibiotics AB023a and AB023b, were separated and purified by preparative chromatographic methods and their structures were determined by extensive NMR and mass spectrometric studies. PMID- 8468241 TI - BMS-181184, a new pradimicin derivative. Screening, taxonomy, directed biosynthesis, isolation and characterization. AB - BMS-181184 is a new semisynthetic pradimicin derivative with a broad-spectrum antifungal activity. In a search for actinomycetes producing BMS-181184, 4 strains of Actinomadura sp. isolated from soil samples were found to produce the antibiotic under conditions of directed biosynthesis. Among them, Actinomadura sp. AB1236 proved most useful in the production of BMS-181184 when fermented in a medium containing D-serine and D-cycloserine. A minor product isolated from the broth of strain AB1236 was identified as the dexylosyl analog of BMS-181184, which was also obtained by acid hydrolysis of BMS-181184. PMID- 8468242 TI - Three novel polyether antibiotics X-14889A, C, and D from a streptomycete. Taxonomy of the producing organism, fermentation production and biological properties of the antibiotics. AB - Antibiotic X-14889A, C, and D are novel polyether antibiotics related to lysocellin and antibiotic X-14873A. They are produced by a streptomycete isolated from a soil of Wisconsin. The antibiotic X-14889C is active against Gram-positive bacteria and exhibits ionophore property. PMID- 8468243 TI - Isolation and characterization of four polyether antibiotics, X-14889A, B, C, and D, closely related to lysocellin and the ferensimycins. AB - Streptomyces sp. X-14889 (NRRL 15517) has been found to produce a number of novel polyether antibiotics and an orange pigment. One of the antibiotics, X-14889B (3) was identified as ferensimycin A, which in turn is an isomer of the well-studied polyether antibiotic, lysocellin (1). Of the three other antibiotics, X-14889C (4) is a lower homolog of ferensimycin A and antibiotics X-14889A (2) and D (5) which are respectively the descarboxy and anhydro-descarboxy forms of this same molecule. The latter compound, X-14889D is of interest as it contains an ether bridge across the terminal tetrahydrofuranyl ring in an analogous relationship to that reported earlier for antibiotics X-14873A (6) and G. PMID- 8468244 TI - Ferrocins, new iron-containing peptide antibiotics produced by bacteria. Isolation, characterization and structure elucidation. AB - Novel iron-containing peptide antibiotics, ferrocins A, B, C and D, have been isolated from the culture filtrate of Pseudomonas fluorescens YK-310. These antibiotics were purified by butanol extraction, followed by column chromatography using adsorption resin, silica gel and preparative reverse-phase HPLC. The structures of ferrocins were elucidated using spectroscopic and degradative methods. Ferrocins contain three hydroxamate moieties per ferric ion which forms an octahedral iron complex. PMID- 8468245 TI - Synthesis of the metabolite N-hydroxy-desferrioxamine B. AB - N-Hydroxy-desferrioxamine B (5), a postulated metabolite of the microbial product desferrioxamine B (1), has been prepared by reduction of the intermediate oxime 6 with sodium cyanoborohydride. The oxime was obtained by selective oxidation of desferrioxamine B with hydrogen peroxide and a catalytic amount of sodium tungstate dihydrate. The iron complex derived from 5 enabled definite proof of the structure of one of four metabolites of desferrioxamine B found in urine samples of patients treated with this drug. PMID- 8468246 TI - Syntheses of the potent inhibitors of neuraminidase, N-(1,2-dihydroxypropyl) derivatives of siastatin B and its 4-deoxy analogs. PMID- 8468247 TI - Structures of enzymatically modified products of arbekacin by methicillin resistant. Staphylococcus aureus. AB - Only a limited number of strains of methicillin-resistant Staphylococcus aureus (MRSA) moderately resistant to arbekacin (ABK) have been isolated clinically. Three inactivated products of ABK have been obtained by reaction with excess amounts of a crude enzyme preparation extracted from an ABK-resistant MRSA strain (MIC, 25 micrograms/ml). The 2"-O-phosphate was the major product together with small amounts of the 6'-N-acetate and the double modification product. The structures of these modification products were determined by MS and NMR spectral analyses. PMID- 8468248 TI - Orally active cephalosporins. III. Synthesis and structure-activity relationships of new 3-heterocyclicthiomethylthio-7 beta-[(Z)- 2-(2-aminothiazol-4-yl)-2 hydroxyiminoacetamido]-3-cephem-4 -carboxylic acids. AB - 3-Heterocyclicthiomethylthio-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2- hydroxyiminoacetamido]-3-cephem-4-carboxylic acids (2) were synthesized. Their antibacterial activity and oral absorbability were much influenced by the structure of heteroaromatic moiety in the side chain at the 3-position of a cephem nucleus. In this cephalosporin series, 3 thiadiazolylthiomethylthiocephalosporins (2k, 2l and 2m) exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, whereas 3-(2-methyl-1,2,3-triazol-4-yl)thiomethylthiocephalosporin (2b) and 3 (pyridin-2-yl)thiomethylthiocephalosporin (2n) showed better oral absorption in mice than the other cephalosporins prepared. The structure-activity relationships of 2 are presented. PMID- 8468249 TI - Synthesis and structure-activity relationships of some 6 beta-acrylamido penicillins. AB - Syntheses are described for penicillins (4b approximately 4i, 5a and 5b) which possess a 6 beta-(2-heteroaryl-3-substituted)-propenamido side-chain of fixed geometry. In vitro results for these compounds against a range of Gram-positive and Gram-negative bacteria showed in most cases good stability against both penicillinase and TEM-1 beta-lactamase; analogues (4b approximately 4i) bearing a 2-(2-aminothiazol-4-yl) unit showed the best intrinsic activity, the cyclohexyl compound (4b) being the most promising. The 1-acetoxyethyl ester (6) of 4b was also prepared; in experimental animal studies the in vivo properties of this compound compared favourably with cefuroxime axetil and are reported together with selected in vivo data for the other compounds. PMID- 8468250 TI - Secondary metabolites by chemical screening. 21. Clonostachydiol, a novel anthelmintic macrodiolide from the fungus Clonostachys cylindrospora (strain FH-A 6607). PMID- 8468251 TI - Metabolic products of microorganisms. 264. Exfoliamycin and related metabolites, new naphthoquinone antibiotics from Streptomyces exfoliatus. PMID- 8468252 TI - Elaiophylin as a rumen fermentation efficiency enhancer. PMID- 8468253 TI - Mer-WF3010, a new member of the papulacandin family. II. Structure determination. PMID- 8468254 TI - FK037, a new parenteral cephalosporin with a broad antibacterial spectrum: synthesis and antibacterial activity. PMID- 8468255 TI - Stereoselective synthesis of BRL 56173, a bicyclic acrylic penicillin highly stable to beta-lactamases. PMID- 8468256 TI - Methods for Escherichia coli identification in food, water and clinical samples based on beta-glucuronidase detection. PMID- 8468258 TI - The effect of the olive phenolic compound, oleuropein, on growth and enterotoxin B production by Staphylococcus aureus. AB - The presence of low concentrations (0.1% w/v) of oleuropein, a phenolic compound extracted from olives, delayed the growth of Staphylococcus aureus in NZ amine A and brain heart infusion media modified by the addition of growth factors and glucose (NZA+ and BHI+), as indicated by changes in conductance, whilst higher concentrations (0.4-0.6% w/v) inhibited growth completely. Intermediate concentrations of oleuropein (0.2%) prevented growth in BHI+ but allowed growth to occur in NZA+ despite an extended lag phase (30 h). Concentrations of oleuropein > 0.2% inhibited growth and production of enterotoxin B in both types of media. Lower levels (0.1%) did not affect the final viable count and production of toxin in BHI+ but decreased the number of viable organisms and reduced the toxin production in NZA+ by eightfold. An increase in the concentration of oleuropein resulted in a decrease in the amount of glucose assimilated and consequently the amount of lactate produced. In addition, oleuropein prevented the secretion of a number of exoproteins. Addition of oleuropein during the exponential phase appeared to have no effect on the growth of Staph. aureus in NZA+. PMID- 8468257 TI - Alternative antigens reduce cross-reactions in an ELISA for the detection of Salmonella enteritidis in poultry. AB - Two alternative antigens for the use in detection of antibodies to salmonellas were investigated: firstly, lipopolysaccharide (LPS) from members of the D2 group, having antigens O: 9, 46, and flagella antigens. Whereas LPS from the D2 group did not discriminate sufficiently with control sera, flagella antigens reacted specifically with antibodies directed to serotype specific H antigens. When flagella antigens were used to screen sera from birds of commercial flocks, however, cross-reactivity between flagella antigens was observed. When both LPS and flagella antigens were used to screen sera from chickens infected with Salmonella enteritidis, the sera gave higher titres with flagella antigens during the early stages of infection, and titres with flagella antigens dropped earlier after infection had ended than titres with lipopolysaccharide. PMID- 8468259 TI - Use of the polymerase chain reaction and 16S rRNA sequences for the rapid detection of Brochothrix spp. in foods. AB - Oligonucleotide primers were designed against rRNA sequences to give a DNA-based PCR assay for the rapid identification/detection of Brochothrix spp. The PCR products could be confirmed by hybridization to an internal oligonucleotide probe. The method successfully and sensitively detected/identified these organisms in pure cultures but was of limited value as a detection method because the detection sensitivity, in relation to conventional plate counts, varied and the assay sensitivity was reduced in the presence of staphylococci. Furthermore, sensitivity was also lost when the assay was applied directly to meat samples. However, a separation step using a lectin (from Agaricus bisporus) immobilized on magnetic beads prior to the PCR assay, allowed the direct detection of low numbers (> 10(2) cfu g-1) of Brochothrix in meat samples within a working day. PMID- 8468260 TI - Separation of bacteria using agglutinins isolated from invertebrates. AB - The agglutination of a selection of Gram-positive and Gram-negative bacteria by the haemolymph and coelomic fluid from several invertebrates was studied. The haemolymph from Lumbricus terrestris and Limulus polyphemus caused the strongest agglutination of most of the bacteria studied. When the agglutinating fraction of Lim. Polyphemus was liganded to magnetic microspheres 53% of the cells in pure cultures of Listeria monocytogenes C200, 15% of Salmonella enteritidis 37782, 92% of Staphylococcus aureus NCDO 949, 19% of Escherichia coli E4936/76 and 65% of E. coli W2-2 were adsorbed to the beads. The immobilized haemolymph from Lumb. terrestris adsorbed 42% of Salm. enteritidis 37782, 64% of E. coli 4936/76 and 27% of Staph. aureus NCDO 1499 cells and the coelomic fluid from Haemopsis sanguisuga adsorbed 42, 48 and 50% of these cultures respectively. With immobilized Haem. sanguisuga agglutinins, 21-27% of Staph. aureus NCDO 2044 cells were recovered from full-fat pasteurized milk and 20-51% from braising steak. Immobilized Lim. polyphemus agglutinins recovered 17-34% of Staph. aureus cells from raw egg. The potential of agglutinins isolated from invertebrates for enhancing rapid microbiological assays of foods is discussed. PMID- 8468261 TI - Adhesion of Lactobacillus acidophilus to avian intestinal epithelial cells mediated by the crystalline bacterial cell surface layer (S-layer). AB - Lactobacillus acidophilus was isolated from washed and homogenized walls of the crop and caecum of an adult fowl. A strain that adhered well in the Fuller adhesion test was subcultured until colonies on Lactobacillus Selective agar changed from rough to smooth. This coincided with a change from aggregate to planktonic growth in liquid medium and a marked loss of ability to adhere. ultrastructure of cells from both types of culture was studied by electron microscopy. An S-layer formed the outermost part of the cell wall in the strongly adherent strain, whereas this layer was covered with polymerized material or was absent in strains that lacked the ability to adhere, or those with reduced adherence. PMID- 8468262 TI - Molecular characterization of Lactobacillus curvatus and Lact. sake isolated from sauerkraut and their application in sausage fermentations. AB - Lactobacillus curvatus and Lact. sake are best adapted to meat fermentations and dominate the flora during the whole process. In fermenting sauerkraut, Leuconostoc mesenteroides subsp. mesenteroides is the major organism only during the early phase. In this environment Lact. curvatus and Lact. sake provide up to 50% of the microbial flora especially of the later phase, depending on the process conditions. Strains of Lact. curvatus and Lact. sake isolated from fermenting sauerkraut were identified by hybridization with species specific 23S rRNA-targeted oligonucleotide probes and further characterized. In 59 of 72 strains, plasmid DNA was detected. Small cryptic plasmids of 20 strains were found to be homologous with pLc2, a 2.6 kb plasmid from Lact. curvatus LTH683, which was originally isolated from meat. The ability to compete was investigated in fermenting sausages of two strains each of Lact. curvatus and Lact. sake isolated from sauerkraut. One strain each of Lact. curvatus and Lact. sake was found to outnumber the meat-borne flora and govern the process. PMID- 8468263 TI - Digoxigenin-labelled inv- and ail-probes for the detection and identification of pathogenic Yersinia enterocolitica in clinical specimens and naturally contaminated pig samples. AB - A non-radioactive colony hybridization method was developed for the rapid detection of Yersinia enterocolitica in primary isolates and for differentiation between pathogenic and non-pathogenic strains. The method is based on, respectively, the presence of the inv-locus in all Yersinia spp. and the presence of the ail-gene in pathogenic Y. enterocolitica only. Hybridization results with ail-probes of 132 strains of Y. enterocolitica were in good agreement with pathogenicity phenotypes as indicated by a tissue culture invasion (TCI) assay and by serotyping. All TCI+ strains and only two TCI- strains were positive by hybridization with ail. Hybridization results with inv- or ail-probes of 150 primary isolates of human, animal or slaughterhouse origin were compared with those of conventional methods to detect and identify Y. enterocolitica. All samples that were positive for Yersinia spp. by cultivation (four of 66) or were positive for pathogenic Y. enterocolitica by cultivation and serotyping (six of 84) were also positive by hybridization with, respectively, the inv- or ail probe. In three slaughterhouse swab samples, in which Yersinia spp. were not detected by cultivation (2%), strong positive hybridization signals were obtained with the inv- and/or ail-probe. Four other swab samples which were negative by cultivation produced weak positive signals by hybridization with inv- and/or ail probes. These results indicate that the method can be used for (1) the identification of pathogenic Y. enterocolitica isolates and (2) the detection of Yersinia spp. in primary isolates of naturally contaminated samples. PMID- 8468264 TI - Numerical taxonomy of Lactobacillus spp. associated with healthy and diseased mucosa of the human intestines. AB - Two-hundred and fifty Lactobacillus strains isolated from healthy and diseased mucosa of human intestines of 75 individuals and 49 reference strains were phenotypically classified using 49 unit characters. Data were processed by the Jaccard (SJ) and Simple Matching (SSM) coefficients, and unweighted pair group algorithm with arithmetic averages. Seventeen major clusters were defined at the 76% SJ-similarity level which approximately correspond to the SSM-level of 91%. Seven clusters could be identified: Lactobacillus plantarum (isolates recovered from 5% of the patients), Lact. casei subsp. rhamnosus (17% of the patients), Lact. casei subsp. pseudoplantarum (5% of the patients), Leuconostoc mesenteroides subsp. mesenteroides (3% of the patients), Lact. buchneri (4% of patients), Lact. reuteri (4% of the patients) and Lact. salivarius subsp. salivarius (9% of the patients). Unassigned clusters 1 and 3 both contained homofermentative Lactobacillus strains. Cluster 1 included the type strains of Lact. crispatus, Lact. acidophilus, Lact. jensenii and Lact. gasseri, and cluster 3, the type strains of Lact. delbrueckii subsp. lactis, Lact. agilis and Lact. casei subsp. tolerans. Clusters 1 and 3 were found in 15% and 25% of the patients, respectively. Unassigned clusters 2, 6, 7, 8 and 10 contained homofermentative Lactobacillus strains but no reference strains. Clusters 11, 12, 15 and 17 were made up of heterofermentative Lactobacillus strains but no reference strains. Phenotypical characteristics of the clusters are given. No obvious trends in species (cluster) composition between different intestinal locations could be noted. Most clusters contained isolates from both diseased and healthy mucosa. Exceptions were cluster 15 and cluster 17 which only included isolates from healthy mucosa, and cluster 11 which only included isolates from diseased mucosa. Cluster 15 was isolated in 12% of the patients, and cluster 11 in 8%. PMID- 8468265 TI - Laboratory study of several enrichment broths for the detection of Salmonella spp. particularly in relation to water samples. AB - The selectivity and efficiency of several enrichment broths used for the the detection of salmonellas were comparatively evaluated under laboratory and environmental conditions. Media with selenite were less efficient in their inhibition of the growth of Gram-positive micro-organisms. Salmonellas grew slowly in tetrathionate broth and in media containing brilliant green. These media inhibited the growth of Salmonella typhi, which grew only in media containing selenite. The results obtained in the experiments with stressed salmonellas indicate that the media selenite F, selenite F with novobiocin, selenite cystine and Rappaport-Vassiliadis (RV/43), in conjunction with the double agar layer technique, showed an optimal efficiency for the detection of stressed salmonellas. When natural samples (freshwater and seawater) were used to evaluate the media, however, those containing malachite green, whether or not supplemented with sodium novobiocin, enhanced the recovery of salmonellas. PMID- 8468266 TI - Safety studies of modified hemoglobin as an oxygen-carrying blood substitute. PMID- 8468268 TI - Therapy-related second malignancies. Proceedings of a symposium. Boston, January 1992. PMID- 8468267 TI - The biology of alkylating-agent cellular injury. AB - Alkylating agents, such as nitrogen mustard, cyclophosphamide, and the nitrosoureas, have been used to treat many malignancies for more than 30 years. It is now clear that they are not only cytotoxic but also mutagenic and carcinogenic. The initial alkylation event, monoadduct formation on ring nitrogens or extra-cyclic oxygens of nucleotide bases, can result in chromosomal loss or single base mutation, both of which can lead to malignant transformation. The bone marrow is particularly sensitive to these events, and acute myelogenous leukemia is the most common malignancy caused by alkylating agents. Mechanisms of genetic damage and mutagenesis are discussed. PMID- 8468269 TI - Cellular, molecular, and carcinogenic effects of radiation. AB - (1) The biologic effects of ionizing radiation at the cellular and molecular levels differ from those of many chemical agents. Radiation is a classic genotoxic agent. The important DNA lesion with respect to its cytotoxic and mutagenic effects appears to be the DNA double strand break, whereas chemotherapeutic alkylating agents induce primarily base damage from adduct formation and cross-linking. Radiation-induced mutations result primarily from large-scale structural changes in DNA as a result of mechanisms such as chromosomal deletions, rearrangements, and homologous recombination, rather than point mutation as generally observed with alkylating agents. Finally, radiation is highly cytotoxic; a significantly increased frequency of specific gene mutations is usually observed only following doses that produce significant cell killing. (2) Radiation may not be a very potent inducer of second malignant tumors, at least in most cases. This prediction is derived from the localized nature of the exposure during clinical radiotherapy, in which the dose to normal tissues is minimized, and from the fact that radiation tends to be cytotoxic rather than mutagenic. The very high doses employed in curative radiotherapy may thus kill potentially transformed cells in the field. An exception to this general prediction may be Hodgkin's disease, in which a relatively large volume of tissue is treated with lower total radiation doses. (3) We have a firm scientific basis on which to predict the carcinogenic effects of radiation at many tissue sites, owing to extensive quantitative epidemiologic data in human populations. Unlike for chemical agents, radiation can be easily detected, and the absorbed dose to critical tissues is precisely measured. Thus, we know about the sensitivity of many target tissues to radiation-induced cancer. (4) A number of factors can modify the carcinogenic effects of radiation. It is likely that important interactive effects will occur between radiation and chemotherapeutic alkylating agents, which may depend upon the timing and order of the treatments as well as the particular agent(s) employed. (5) Genetic predisposition to radiation-induced cancer may be a confounding factor in the prediction of its effects in any given individual. PMID- 8468270 TI - Mutagenesis after therapy for Hodgkin's disease. AB - Therapy for Hodgkin's disease has been associated with a significant increase in risk for second cancers. To begin an investigation of the association of therapy induced genetic damage with this risk, somatic mutations at the hypoxanthine phosphoribosyltransferase locus were measured in lymphocytes from patients previously treated for Hodgkin's disease. The results demonstrate that a subset of patients have persistently elevated mutation frequencies, perhaps suggesting that these individuals are among those at significant risk of second cancer development. PMID- 8468271 TI - Acute leukemia after the treatment of Hodgkin's disease. AB - The risk of developing a secondary acute leukemia or myelodysplastic syndrome after the treatment of Hodgkin's disease is discussed on the basis of the results reported from large series with prolonged follow-up. It appears that the risk mainly depends upon the treatment strategy and certain host-related factors such as older age. Radiation therapy used alone is associated with the lowest risk, combination mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy plus irradiation with the highest risk, and the risk of MOPP chemotherapy alone being in between the two. Splenectomy and probably splenic irradiation may also add to the risk. In long-term, surviving patients continuously free of Hodgkin's disease, the cumulative probability of second leukemia is low, with a high risk period which can be limited to the 10 years following the end of curative therapy. Finally, the impact of secondary leukemia on long-term survival is limited and far less than that of second tumors. PMID- 8468272 TI - Solid second cancers following Hodgkin's disease. AB - Patients treated for Hodgkin's disease with radiation therapy, chemotherapy, or both, are often cured with potential lives ahead of them. It is now obvious, however, that many of these patients will develop solid tumors in the years after their successful treatment for Hodgkin's disease. These tumors include non Hodgkin's lymphomas, lung cancers, sarcomas, and gastrointestinal malignancies, as well as other solid tumors. Understanding the epidemiology of the development of these solid tumors should allow us to design therapies in the future that diminish the risk of developing these second cancers. PMID- 8468273 TI - Second tumors after treatment of childhood malignancies. AB - The occurrence of a second malignancy represents a serious complication of childhood cancer. With the introduction of more intensive multiagent therapy for childhood cancers, not only are a greater proportion of children surviving their initial cancer, but also they now may be at greater risk for developing a second malignancy. The larger studies indicate that the cumulative incidence of second cancers may be as high as 12% at 20 years following the initial cancer. The most consistent finding of the larger studies is that the elevated risk of a second cancer remains relatively constant over time, but the absolute risk increases substantially as the length of follow-up increases. There are treatment-related risk factors, such as solid tumors within irradiated fields and secondary leukemias following alkylating therapy. Retinoblastoma represents one example of the role of genetic predisposition in second cancers. It is imperative that survivors of childhood cancer be closely followed to determine the occurrence of second cancers, particularly those that may occur many years following the original childhood cancer. Research needs to be directed toward the identification of treatment, as well as genetic and life style risk factors. Intervention, through modifications of treatment protocols and implementation of preventive programs, may have a future role in reducing the occurrence of second cancers. PMID- 8468274 TI - Risk factors for the development of secondary malignancies after marrow transplantation. AB - Bone marrow transplantation is associated with several risk factors that may predispose patients to the development of a new malignancy post-transplant. Several types of malignancies, including lymphoproliferative disorders, new leukemias, and solid tumors have been observed. Risk factors include treatment of acute graft-versus-host disease with monoclonal or polyclonal antibodies, total body irradiation, HLA nonidentity, and T-cell depletion. It is currently unknown whether longer follow-up will show a further increase or decline in the incidence of secondary tumors. PMID- 8468275 TI - Tumors after renal and cardiac transplantation. AB - Organ transplant recipients treated with immunosuppressive therapy are prone to develop malignancies particularly squamous cell carcinomas of the skin, non Hodgkin's lymphomas, Kaposi's sarcomas, carcinomas of the vulva and perineum, in situ carcinomas of the uterine cervix, renal carcinomas, hepatomas, and various sarcomas. The earliest tumors to appear are the Kaposi's sarcoma at an average of 21 months after transplantation, and the latest are carcinomas of the vulva and perineum, at an average of 112 months after transplantation. The tumors that develop in cardiac allograft recipients compared with renal transplant recipients are predominantly non-Hodgkin's lymphomas and more rarely, skin, uterine cervical and vulvar tumors. Major factors accounting for these differences are the intensity of immunosuppressive therapy given to the cardiac patients and the much longer follow-up of the renal allograft recipients. PMID- 8468276 TI - Treatment of therapy-related acute myelogenous leukemia and myelodysplastic syndromes. AB - The number of cases of therapy-related acute myelogenous leukemia and myelodysplastic syndromes has risen with the advances of successful combination chemotherapy. Unfortunately, the therapy-related diseases are difficult to treat. Aggressive induction chemotherapy can induce a complete remission, but the remission duration is short. Differentiating agents, hormonal agents, and growth factors have all been disappointing. Allogeneic bone marrow transplantation remains the only curative approach. PMID- 8468277 TI - Gene to ultrastructure: the case of the flagellar basal body. PMID- 8468278 TI - Highly selective binding of nascent polypeptides by an Escherichia coli chaperone protein in vivo. AB - Chaperone proteins bind to newly synthesized polypeptides and assist in various assembly reactions. The Escherichia coli chaperone protein SecB binds precursors of exported proteins and assists in export. In vitro, SecB can bind to many unfolded proteins. In this report, we demonstrate that SecB binding in vivo is highly selective; the major polypeptides that are bound by SecB are nascent precursors of the exported proteins maltose-binding protein (MBP), LamB, OmpF, and OmpA. These results support the hypothesis that the primary physiological function of SecB is to stimulate protein export. By interacting with nascent polypeptides, SecB probably stimulates their cotranslational association with the membrane-bound protein translocation apparatus. PMID- 8468279 TI - Unipolar localization and ATPase activity of IcsA, a Shigella flexneri protein involved in intracellular movement. AB - Shigella flexneri uses elements of the host cell cytoskeleton to move within cells and from cell to cell. IcsA, an S. flexneri protein involved in this movement, was purified and studied in vitro. IcsA bound the radiolabelled ATP analog 3'(2')-O-(4-benzoyl)benzoyl-ATP and hydrolyzed ATP. In addition, the surface localization of IcsA on both extracellular and intracellular shigellae was unipolar. Further, in HeLa cells infected with shigellae, IcsA antiserum labelled the actin tail throughout its length, thereby suggesting that IcsA interacts with elements within the tail. Localization of IcsA within the tail at a distance from the bacterium would require its secretion; we demonstrate here that in vitro IcsA is secreted into the culture supernatant in a cleaved form. PMID- 8468280 TI - Genetic construction and functional analysis of hybrid polyketide synthases containing heterologous acyl carrier proteins. AB - The gene that encodes the acyl carrier protein (ACP) of the actinorhodin polyketide synthase (PKS) of Streptomyces coelicolor A3(2) was replaced with homologs from the granaticin, oxytetracycline, tetracenomycin, and putative frenolicin polyketide synthase gene clusters. All of the replacements led to expression of functional synthases, and the recombinants synthesized aromatic polyketides similar in chromatographic properties to actinorhodin or to shunt products produced by mutants defective in the actinorhodin pathway. Some regions within the ACP were also shown to be interchangeable and allow production of a functional hybrid ACP. Structural analysis of the most abundant polyketide product of one of the recombinants by electrospray mass spectrometry suggested that it is identical to mutactin, a previously characterized shunt product of an actVII mutant (deficient in cyclase and dehydrase activities). Quantitative differences in the product profiles of strains that express the various hybrid synthases were observed. These can be explained, at least in part, by differences in ribosome-binding sites upstream of each ACP gene, implying either that the ACP concentration in some strains is rate limiting to overall PKS activity or that the level of ACP expression also influences the expression of another enzyme(s) encoded by a downstream gene(s) in the same operon as the actinorhodin ACP gene. These results reaffirm the idea that construction of hybrid polyketide synthases will be a useful approach for dissecting the molecular basis of the specificity of PKS-catalyzed reactions. However, they also point to the need for reducing the chemical complexity of the approach by minimizing the diversity of polyketide products synthesized in strains that produce recombinant polyketide synthases. PMID- 8468281 TI - Energy flux and osmoregulation of Saccharomyces cerevisiae grown in chemostats under NaCl stress. AB - The energetics and accumulation of solutes in Saccharomyces cerevisiae were investigated for cells grown aerobically in a chemostat under NaCl stress and glucose limitation. Changed energy requirements in relation to external salinity were examined by energy balance determinations performed by substrate and product analyses, with the latter including heat measurements by microcalorimetry. In both 0 and 0.9 M NaCl cultures, the catabolism was entirely respiratory at the lowest dilution rates tested but shifted to a mixed respiratory-fermentative metabolism at higher dilution rates. This shift occurred at a considerably lower dilution rate for salt-grown cells. The intracellular solute concentrations, as calculated on the basis of intracellular soluble space determinations, showed that the internal Na+ concentration increased from about 0.02 molal in basal medium to about 0.18 molal in 0.9 M NaCl medium, while intracellular K+ was maintained around 0.29 molal despite the variation in external salinity. The intracellular glycerol concentration increased from below 0.05 molal at low salinity to about 1.2 molal at 0.9 M NaCl. The concentrations of the internal solutes, however, changed insignificantly with growth rate and energy metabolism. The additional maintenance energy expenditure for growth at 0.9 M NaCl was, depending on the growth rate, 14 to 31% of the total energy requirement for growth at 0 M NaCl. Including the energy conserved in glycerol, the total additional energy demand for growth at 0.9 M NaCl corresponded to 28 to 51% of the energy required for growth at 0 M NaCl. PMID- 8468282 TI - Characterization of the Escherichia coli F factor traY gene product and its binding sites. AB - The traY gene product (TraYp) from the Escherichia coli F factor has previously been purified and shown to bind a DNA fragment containing the F plasmid oriT region (E. E. Lahue and S. W. Matson, J. Bacteriol. 172:1385-1391, 1990). To determine the precise nucleotide sequence bound by TraYp, DNase I footprinting was performed. The TraYp-binding site is near, but not coincident with, the site that is nicked to initiate conjugative DNA transfer. In addition, a second TraYp binding site, which is coincident with the mRNA start site at the traYI promoter, is described. The Kd for each binding site was determined by a gel mobility shift assay. TraYp exhibits a fivefold higher affinity for the oriT binding site compared with the traYI promoter binding site. Hydrodynamic studies were performed to show that TraYp is a monomer in solution under the conditions used in DNA binding assays. Early genetic experiments implicated the traY gene product in the site- and strand-specific endonuclease activity that nicks at oriT (R. Everett and N. Willetts, J. Mol. Biol. 136:129-150, 1980; S. McIntire and N. Willetts, Mol. Gen. Genet. 178:165-172, 1980). As this activity has recently been ascribed to helicase I, it was of interest to see whether TraYp had any effect on this reaction. Addition of TraYp to nicking reactions catalyzed by helicase I showed no effect on the rate or efficiency of oriT nicking. Roles for TraYp in conjugative DNA transfer and a possible mode of binding to DNA are discussed. PMID- 8468283 TI - Mechanism of adverse conditions causing lack of flagella in Escherichia coli. AB - Escherichia coli lacks flagella when grown in tryptone broth in the presence of various adverse conditions (C. Li, C. J. Louise, W. Shi, and J. Adler, J. Bacteriol. 175:2229-2235, 1993). Now, the synthesis, rather than the degradation, of flagellin was shown to be inhibited. Studies of transcriptional fusions of flagellar operons to the lacZ gene revealed that transcription of the flagellar genes was reduced in cells grown under these adverse conditions. Increasing gene dosage of the flhD operon by a plasmid partially suppressed the nonflagellation caused by some adverse conditions. The signal which shuts off the synthesis of flagella under adverse conditions remains to be discovered. This shutting-off process does not result from catabolite repression or from signals from the chemotaxis system. PMID- 8468284 TI - Plasmolysis bays in Escherichia coli: are they related to development and positioning of division sites? AB - Plasmolysis bays, induced in Escherichia coli by hypertonic treatment, are flanked by zones of adhesion between the plasma membrane and the cell wall. To test the proposition of Cook et al. (W. R. Cook, F. Joseleau-Petit, T. J. MacAlister, and L. I. Rothfield, Proc. Natl. Acad. Sci. USA 84:7144-7148, 1987) that these zones, called periseptal annuli, play a role in determining the division site, we analyzed the positions of these zones by phase-contrast and electron microscopy. In situ treatment of cells grown in agar showed that the youngest cell pole was the most susceptible to plasmolysis, whereas the constriction site was resistant. Lateral bays occurred only at some distance from a polar bay or a resistant constriction site. Orienting cells with their most prominently plasmolyzed polar bay in one direction showed that the lateral bays were always displaced away from the polar bay at about half the distance to the other cell pole. If no poles were plasmolyzed, lateral bays occurred either in the centers of nonconstricting cells or at the 1/4 or 3/4 position of cell length in constricting cells. The asymmetric positions of lateral plasmolysis bays, caused by their abrupt displacement in the presence of polar bays or constriction sites, does not confirm the periseptal annulus model (Cook et al.), which predicts a gradual and symmetric change in the position of lateral bays with increasing cell length. Our analysis indicates that plasmolysis bays have no relation to the development and positioning of the future division site. PMID- 8468285 TI - Relevance of charged groups for the integrity of the S-layer from Bacillus coagulans E38-66 and for molecular interactions. AB - In this paper, the importance of charged amino and carboxyl groups for the integrity of the cell surface layer (S-layer) lattice from Bacillus coagulans E38 66 and for the self-assembly of the isolated subunits was investigated. Amidination of the free amino groups which preserved their positive net charge had no influence on both. On the other hand, acetylation and succinylation, which converted the amino groups into either neutral or negatively charged groups, and amidation of carboxyl groups were accompanied by the disintegration or at least by the loss of the regular structure of the S-layer lattice. Treatment of S-layer monolayers with the zero-length cross-linker carbodiimide led to the introduction of peptide bonds between activated carboxyl groups and amino groups from adjacent subunits. This clearly indicated that in the native S-layer lattice the charged groups are located closely enough for direct electrostatic interactions. Under disrupting conditions in which the S-layer polypeptide chains were unfolded, 58% of the Asx and Glx residues could be amidated, indicating that they occur in the free carboxylic acid form. As derived from chemical modification of monolayer self-assembly products, about 90% of the lysine and 70% of the aspartic and glutamic acid residues are aligned on the surface of the S-layer protein domains. This corresponded to 45 amino groups and to 63 carboxyl groups per S-layer subunit. Labelling experiments with macromolecules with different sizes and charges and adsorption studies with ion-exchange particles revealed a surplus of free carboxyl groups on the inner and on the outer faces of the S-layer lattice. Since the carboxyl groups on the outer S-layer face were accessible only for protein molecules significantly smaller then the S-layer protomers or for positively charged, thin polymer chains extending from the surface of ion exchange beads, the negatively charged sites must be located within indentations of the corrugated S-layer protein network. This was in contrast to the carboxyl groups on the inner S-layer face, which were found to be exposed on elevations of the S-layer protein domains (D. Pum, M. Sara, and U.B. Sleytr, J. Bacteriol. 171:5296-5303, 1989). PMID- 8468286 TI - A mutation of Escherichia coli SecA protein that partially compensates for the absence of SecB. AB - The Escherichia coli SecB protein is a cytosolic chaperone protein that is required for rapid export of a subset of exported proteins. To aid in elucidation of the activities of SecB that contribute to rapid export kinetics, mutations that partially suppressed the export defect caused by the absence of SecB were selected. One of these mutations improves protein export in the absence of SecB and is the result of a duplication of SecA coding sequences, leading to the synthesis of a large, in-frame fusion protein. Unexpectedly, this mutation conferred a second phenotype. The secA mutation exacerbated the defective protein export caused by point mutations in the signal sequence of pre-maltose-binding protein. One explanation for these results is that the mutant SecA protein has sustained a duplication of its binding site(s) for exported protein precursors so that the mutant SecA is altered in its interaction with precursor molecules. PMID- 8468287 TI - Cloning and nucleotide sequence of the Myxococcus xanthus lon gene: indispensability of lon for vegetative growth. AB - The lon gene of Escherichia coli is known to encode protease La, an ATP-dependent protease associated with cellular protein degradation. A lon gene homolog from Myxococcus xanthus, a soil bacterium which differentiates to form fruiting bodies upon nutrient starvation, was cloned and characterized by use of the lon gene of E. coli as a probe. The nucleotide sequence of the M. xanthus lon gene was determined. It contains an open reading frame that encodes a 92-kDa protein consisting of 817 amino acid residues. The deduced amino acid sequence of the M. xanthus lon gene product showed 60 and 56% identity with those of the E. coli and Bacillus brevis lon gene products, respectively. Analysis of an M. xanthus strain carrying a lon-lacZ operon fusion suggested that the lon gene is similarly expressed during vegetative growth and development in M. xanthus. In contrast to that of E. coli, the M. xanthus lon gene was shown to be essential for cell growth, since a null mutant could not be isolated. PMID- 8468288 TI - Construction of a Pseudomonas hybrid strain that mineralizes 2,4,6 trinitrotoluene. AB - A bacterium, Pseudomonas sp. strain C1S1, able to grow on 2,4,6-trinitrotoluene (TNT), 2,4- and 2,6-dinitrotoluene, and 2-nitrotoluene as N sources, was isolated. The bacterium grew at 30 degrees C with fructose as a C source and accumulated nitrite. Through batch culture enrichment, we isolated a derivative strain, called Pseudomonas sp. clone A, which grew faster on TNT and did not accumulate nitrite in the culture medium. Use of TNT by these two strains as an N source involved the successive removal of nitro groups to yield 2,4- and 2,6 dinitrotoluene, 2-nitrotoluene, and toluene. Transfer of the Pseudomonas putida TOL plasmid pWW0-Km to Pseudomonas sp. clone A allowed the transconjugant bacteria to grow on TNT as the sole C and N source. All bacteria in this study, in addition to removing nitro groups from TNT, reduced nitro groups on the aromatic ring via hydroxylamine to amino derivatives. Azoxy dimers probably resulting from the condensation of partially reduced TNT derivatives were also found. PMID- 8468289 TI - Relationships between C4 dicarboxylic acid transport and chemotaxis in Rhizobium meliloti. AB - The relationship between chemotaxis and transport of C4 dicarboxylic acids was analyzed with Rhizobium meliloti dct mutants defective in one or all of the genes required for dicarboxylic acid transport. Succinate, malate, and fumarate were moderately potent chemoattractants for wild-type R. meliloti and appeared to share a common chemoreceptor. While dicarboxylate transport is inducible, taxis to succinate was shown to be constitutive. Mutations in the dctA and dctB genes both resulted in the reduction, but not elimination, of chemotactic responses to succinate, indicating that transport via DctA or chemosensing via DctB is not essential for C4 dicarboxylate taxis, although they appear to contribute to it. Mutations in dctD and rpoN genes did not affect taxis to succinate. Aspartate, which is also transported by the dicarboxylate transport system, elicited strong chemotactic responses via a chemoreceptor distinct from the succinate-malate fumarate receptor. Taxis to aspartate was unaltered in dctA and dctB mutants but was considerably reduced in both dctD and rpoN mutants, indicating that aspartate taxis is strongly dependent on elements responsible for transcriptional activation of dctA. Methylation and methanol release experiments failed to show a significant increase in methyl esterification of R. meliloti proteins in response to any of the attractants tested. PMID- 8468290 TI - Expression of the Rhodobacter sphaeroides hemA and hemT genes, encoding two 5 aminolevulinic acid synthase isozymes. AB - The nucleotide sequences of the Rhodobacter sphaeroides hemA and hemT genes, encoding 5-aminolevulinic acid (ALA) synthase isozymes, were determined. ALA synthase catalyzes the condensation of glycine and succinyl coenzyme A, the first and rate-limiting step in tetrapyrrole biosynthesis. The hemA and hemT structural gene sequences were 65% identical to each other, and the deduced HemA and HemT polypeptide sequences were 53% identical, with an additional 16% of aligned amino acids being similar. HemA and HemT were homologous to all characterized ALA synthases, including two human ALA synthase isozymes. In addition, they were evolutionarily related to 7-keto-8-aminopelargonic acid synthetase (BioF) and 2 amino-3-ketobutyrate coenzyme A ligase (Kbl), enzymes which catalyze similar reactions. Two hemA transcripts were identified, both expressed under photosynthetic conditions at levels approximately three times higher than those found under aerobic conditions. A single transcriptional start point was identified for both transcripts, and a consensus sequence at this location indicated that an Fnr-like protein may be involved in the transcriptional regulation of hemA. Transcription of hemT was not detected in wild-type cells under the physiological growth conditions tested. In a mutant strain in which the hemA gene had been inactivated, however, hemT was expressed. In this mutant, hemT transcripts were characterized by Northern (RNA) hybridization, primer extension, and ribonuclease protection techniques. A small open reading frame of unknown function was identified upstream of, and transcribed in the same direction as, hemA. PMID- 8468291 TI - 5-Aminolevulinic acid availability and control of spectral complex formation in hemA and hemT mutants of Rhodobacter sphaeroides. AB - In the photosynthetic bacterium Rhodobacter sphaeroides, two genes, hemA and hemT, each encode a distinct 5-aminolevulinic acid (ALA) synthase isozyme (E. L. Neidle and S. Kaplan, J. Bacteriol. 175:2292-2303, 1993). This enzyme catalyzes the first and rate-limiting step in a branched pathway for tetrapyrrole formation, leading to the biosynthesis of hemes, bacteriochlorophylls, and corrinoids. In an attempt to determine the functions of hemA and hemT, mutant strains were constructed with specific chromosomal disruptions. These chromosomal disruption allowed hemA and hemT to be precisely localized on the larger and smaller of two R. sphaeroides chromosomes, respectively. Mutants carrying a single hemA or hemT disruption grew well without the addition of ALA, whereas a mutant, HemAT1, in which hemA and hemT had both been inactivated required exogenous ALA for growth. The growth rates, ALA synthase enzyme levels, and the amounts of bacteriochlorophyll-containing intracytoplasmic membrane spectral complexes of all strains were compared. Under photosynthetic growth conditions, the levels of bacteriochlorophyll, carotenoids, and B800-850 and B875 light harvesting complexes were significantly lower in the Hem mutants than in the wild type. In the mutant strains, available bacteriochlorophyll appeared to be preferentially targeted to the B875 light-harvesting complex relative to the B800 850 complex. In strain HemAT1, the amount of B800-850 complex varied with the concentration of ALA added to the growth medium, and under conditions of ALA limitation, no B800-850 complexes could be detected. In the Hem mutants, there were aberrant transcript levels corresponding to the puc and puf operons encoding structural polypeptides of the B800-850 and B875 complexes. These results suggest that hemA and hemT expression is coupled to the genetic control of the R. sphaeroides photosynthetic apparatus. PMID- 8468292 TI - AppppA-binding protein E89 is the Escherichia coli heat shock protein ClpB. AB - Dinucleotide AppppA (5',5'''-P1,P4-diadenosine tetraphosphate) is rapidly synthesized in Escherichia coli cells during heat shock. apaH mutants lack AppppN hydrolase activity and, therefore, contain constitutively levels of AppppA, which affect several cellular processes. However, the precise role of AppppA remains undetermined. Photo-crosslinking experiments with radioactively labelled azido AppppA have shown that a number of proteins, including heat shock proteins DnaK and GroEL, specifically bind to AppppA. Several other unidentified proteins (C40, C45, and E89) also bind strongly to AppppA. In this work, we have identified the AppppA-binding protein E89 as heat shock protein ClpB. In addition, since ClpB belongs to a family of proteins implicated in proteolysis, we have examined the effects of apaH mutants on protein degradation. Constitutively elevated levels of AppppA stimulate lon-independent proteolysis only in heat-shocked cells. We also show that overproduction of ClpB from a plasmid rescues apaH mutants from sensitivity to killing by heat. PMID- 8468293 TI - Mutational analysis of segmental stabilization of transcripts from the Zymomonas mobilis gap-pgk operon. AB - In Zymomonas mobilis, the genes encoding glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase are transcribed together from the gap-pgk operon. However, higher levels of the former enzyme are present in the cytoplasm because of increased stability of a 5' segment containing the gap coding region. This segment is bounded by an upstream untranslated region which can be folded into many stem-loop structures and a prominent intercistronic stem-loop. Mutations eliminating a proposed stem-loop in the untranslated region or the intercistronic stem-loop resulted in a decrease in the stability and pool size of the 5' gap segment. Site-specific mutations in the unpaired regions of both of these stems also altered the message pools. Elimination of the intercistronic stem appeared to reduce the endonucleolytic cleavage within the pgk coding region, increasing the stability and abundance of the full-length message. DNA encoding the prominent stem-loop at the 3' end of the message was shown to be a transcriptional terminator both in Z. mobilis and in Escherichia coli. This third stem-loop region (part of the transcriptional terminator) was required to stabilize the full-length gap-pgk message. PMID- 8468294 TI - Regulation of sigma B levels and activity in Bacillus subtilis. AB - The sigB operon of Bacillus subtilis encodes sigma B plus three additional proteins (RsbV, RsbW, and RsbX) that regulate sigma B activity. Using an anti sigma B monoclonal antibody to monitor the levels of sigma B protein, PSPAC to control the expression of the sigB operon, and a ctc-lacZ reporter system to monitor sigma B activity, we observed that the rsbV and rsbW products control sigma B activity at the ctc promoter independently of their effects on sigma B levels. In contrast, RsbX was found to have no effect on expression of ctc when the sigB operon was controlled by PSPAC. The data are consistent with RsbV and RsbW being regulators of sigma B activity and RsbX acting primarily as a negative regulator of sigB operon expression. Evidence that stationary-phase induction of the sigma B-dependent ctc promoter is accomplished by a reduction in RsbW dependent inhibition of sigma B activity is also presented. In addition, Western blot (immunoblot) analyses of sigB operon expression demonstrated that sigma B accumulation is coupled to the synthesis of its primary inhibitor (RsbW). This finding is consistent with RsbW and sigma B being present within the cell in equivalent amounts, a circumstance that would permit RsbW to directly influence sigma B activity by a direct protein-protein interaction. PMID- 8468295 TI - Genetic evidence that promoter P2 is the physiologically significant promoter for the pyrBI operon of Escherichia coli K-12. AB - The pyrBI operon of Escherichia coli K-12 encodes the two nonidentical subunits of the pyrimidine biosynthetic enzyme aspartate transcarbamylase (ATCase). Expression of this operon is negatively regulated by pyrimidine availability primarily through UTP-sensitive transcriptional attenuation and, to a lesser extent, at the level of transcriptional initiation. Previous studies indicated that the pyrBI operon was transcribed from tandem sigma 70 promoters designated P1 and P2, with the large majority of transcription initiated at the more downstream promoter P2. To more clearly define the roles of these promoters, mutations that severely impair or inactivate individual promoters were constructed in the chromosomal pyrBI operon, and their effects on ATCase synthesis were measured. In cells grown under conditions of either pyrimidine excess or pyrimidine limitation, more than 99% of all ATCase synthesis was directed by transcripts initiated at promoter P2, indicating that it is the only physiologically significant pyrBI promoter. However, mutations that effectively inactivate promoter P1 caused a 15% reduction in ATCase levels, apparently by inhibiting transcription from promoter P2 by an unknown mechanism. Support for this explanation was provided by the demonstration that little, if any, transcriptional initiation occurred at promoter P1 in a transcriptional fusion vector whereas a high level of transcription was initiated at promoter P2 in an equivalent construction. Our results also provide evidence for pyrimidine mediated regulation of transcriptional initiation at promoter P2 over a severalfold range and show that cells can grow reasonably well with very low levels of ATCase, apparently because of changes in the concentration of allosteric effectors that increase the specific activity of the enzyme. PMID- 8468296 TI - Structures of genes nasA and nasB, encoding assimilatory nitrate and nitrite reductases in Klebsiella pneumoniae M5al. AB - Klebsiella pneumoniae can use nitrate and nitrite as sole nitrogen sources during aerobic growth. Assimilatory nitrate and nitrite reductases convert nitrate through nitrite to ammonium. We report here the molecular cloning of the nasA and nasB genes, which encode assimilatory nitrate and nitrite reductase, respectively. These genes are tightly linked and probably form a nasBA operon. In vivo protein expression and DNA sequence analysis revealed that the nasA and nasB genes encode 92- and 104-kDa proteins, respectively. The NASA polypeptide is homologous to other prokaryotic molybdoenzymes, and the NASB polypeptide is homologous to eukaryotic and prokaryotic NADH-nitrite reductases. The narL gene product positively regulates expression of the structural genes for respiratory nitrate reductase, narGHJI. Surprisingly, we found that the nasBA operon is tightly linked to the narL-narGHJI region in K. pneumoniae, even though the nitrate assimilatory and respiratory enzymes serve different physiological functions. PMID- 8468298 TI - Choline transport activity in Staphylococcus aureus induced by osmotic stress and low phosphate concentrations. AB - Uptake of [14C]choline upon hyperosmotic stress of exponential-phase Staphylococcus aureus cultures in a complex medium occurred after a delay of 2.5 to 3.5 h. This uptake could be prevented by chloramphenicol, suggesting that it occurred via an inducible transport system. Radioactivity from [14C]choline was accumulated as [14C]glycine betaine. However, neither choline nor glycine betaine could act as the major carbon and energy source for the organism, suggesting that choline was not metabolized beyond glycine betaine. Assay of choline transport activity in cells grown under different conditions in defined media revealed that osmotic stress was mainly responsible for the induction, but choline gave a further increase in induction. The system was not induced in anaerobically grown cells. Choline transport activity was repressed by glycine betaine and proline betaine, suggesting that these compounds are corepressors. Choline transport activity was not induced in cells osmotically stressed by 1 M potassium phosphate or 0.5 M sodium phosphate, but was induced in cells grown in low-phosphate medium in the absence of osmotic stress. This suggests that there is a connection between the phosphate and osmotic stress regulons. Choline transport was energy and Na+ dependent and had a Km of 46 microM and a maximum rate of transport (Vmax) of 54 nmol/min/mg (dry weight). The results of competition studies suggested that N-methyl and an alcohol group or aldehyde groups at the ends of the molecule were important in its recognition by the system. Glycine betaine was not a highly effective competitor, suggesting that its transport system and the choline transport system were distinct from each other. Choline transport was highly susceptible to a variety of inhibitors, which may be related to the greater dependence on respiratory metabolism of cells grown in the presence of high NaC1 concentrations. PMID- 8468297 TI - Sites and gene products involved in lambdoid phage DNA packaging. AB - 21 is a temperate lambdoid coliphage, and the genes that encode the head proteins of lambda and 21 are descended from a common ancestral bacteriophage. The sequencing of terminase genes 1 and 2 of 21 was completed, along with that of a segment at the right end of 21 DNA that includes the R4 sequence. The R4 sequence, a site that is likely involved in termination of DNA packaging, was found to be very similar to the R4 sequences of lambda and phi 80, suggesting that R4 is a recognition site that is not phage specific. DNA packaging by 21 is dependent on a host protein, integration host factor. A series of mutations in gene 1 (her mutations), which allow integration host factor-independent DNA packaging by 21, were found to be missense changes that affect predicted alpha helixes in gp1. gp2, the large terminase subunit, is predicted to contain an ATP binding domain and, perhaps, a second domain important for the cos-cutting activity of terminase. orf1, an open reading frame analogous in position to FI, a lambda gene involved in DNA packaging, shares some sequence identity with FI. orf1 was inactivated with nonsense and insertion mutations; these mutations were found not to affect phage growth. 21 was also not able to complement a lambda FI mutant. PMID- 8468299 TI - The Rhodobacter capsulatus chlorin reductase-encoding locus, bchA, consists of three genes, bchX, bchY, and bchZ. AB - The bchA locus of Rhodobacter capsulatus codes for the chlorin reductase enzyme in the bacteriochlorophyll synthesis pathway. Previous work has suggested that this locus might encompass a single gene. We have sequenced the bchA locus and found it to contain three coding segments, which we designate bchX, bchY, and bchZ. Each coding segment contains its own translational initiation sequence and follows codon utilization patterns consistent with those of previously published R. capsulatus genes. When various regions of the bchA locus and flanking sequences were subcloned into an expression vector and expressed in Escherichia coli, the three coding segments were all expressed as separate peptides. Finally, conservation of amino acid sequences between bchX and a subunit of the protochlorophyllide reductase (bchL, 34% identity) and the nitrogenase Fe protein (nifH, 30 to 37% identity) suggests structural and mechanistic commonalities among all three proteins. PMID- 8468301 TI - Sequence of the gene coding for ammonia monooxygenase in Nitrosomonas europaea. AB - Nitrosomonas europaea, a chemolithotrophic bacterium, was found to contain two copies of the gene coding for the presumed active site polypeptide of ammonia monooxygenase, the 32-kDa acetylene-binding polypeptide. One copy of this gene was cloned, and its complete nucleotide sequence is presented. Immediately downstream of this gene, in the same operon, is the gene for a 40-kDa polypeptide that copurifies with the ammonia monooxygenase acetylene-binding polypeptide. The sequence of the first 692 nucleotides of this structural gene, coding for about two-thirds of the protein, is presented. These sequences are the first sequences of protein-encoding genes from an ammonia-oxidizing autotrophic nitrifying bacterium. The two protein sequences are not homologous with the sequences of any other monooxygenase. From radioactive labelling of ammonia monooxygenase with [14C]acetylene it was determined that there are 23 nmol of ammonia monooxygenase per g of cells. The kcat of ammonia monooxygenase for NH3 in vivo was calculated to be 20 s-1. PMID- 8468300 TI - Structure, function, and regulation of the kilB locus of promiscuous plasmid RK2. AB - The kil-kor regulon of the self-transmissible, broad-host-range plasmid RK2 is a unique network with eight coregulated operons. Among the genes encoded by the kil kor regulon are trfA, which encodes the replication initiator, and several kil loci (kilA, kilB, kilC, and kilE), each of which is lethal to the host cell in the absence of appropriate negative regulatory elements encoded by the korA, korB, korC, and korE determinants. We have proposed that the functions of the kil loci are related to RK2 maintenance or host range. Here, we report the nucleotide sequence of a 2.44-kb region that includes the lethal kilB determinant. We identified the first three genes of the kilB operon (designated klbA, klbB, and klbC), and we determined by deletion analysis that the host-lethal phenotype requires klbB. The predicted amino acid sequence of the 34,995-Da klbA product reveals a potential ATP-binding fold. The klbB product is predicted to be a membrane protein with a molecular mass of 15,012 Da with homology to the RK2 KlaC membrane protein encoded by the kilA operon. The amino acid sequence of the 12,085-Da klbC product contains a perfect match to the leucine zipper motif common to eukaryotic regulatory proteins. Primer extension analysis revealed unambiguously that transcription of the kilB operon begins 46 nucleotides upstream of klbA. No transcription was initiated from the sequence previously presumed by other investigators to be the kilB promoter. The abundance of kilB transcripts is reduced in the presence of KorB, consistent with the prediction that KorB acts at the level of transcription. A degenerate KorB-binding site that contains a perfect half-palindrome overlaps the kilB promoter, but this site is insufficient for regulation by KorB. The region containing a KorB-binding site located 183 bp upstream of the transcriptional start is required for regulation by KorB, indicating that KorB acts at a distance to regulate transcription of kilB. Our studies with the mutant plasmid pRP101, a transfer-defective derivative of the RK2-like plasmid RP4, demonstrated that the kilB operon includes the conjugal transfer and surface exclusion genes of the Tra2 region. Nucleotide sequence analysis revealed that the transposon Tn7 insertion in pRP101 is located in the klbC gene, and complementation analysis showed that this mutation has a strong polar effect on the expression of genes for conjugal transfer and surface exclusion located several kilobases downstream. A klbA mutant was constructed and found to be both transfer defective and complementable, thus, demonstrating a requirement was constructed and found to be both transfer defective and complementable, thus demonstrating a requirement for klbA product in plasmid transmissibility. These results have demonstrated a role for the kilB operon in conjugal transfer. The kil-kor regulon of RK2 is the only known example of plasmid-mediated coregulation of replication and transfer. PMID- 8468302 TI - Expression of gonococcal transferrin-binding protein 1 causes Escherichia coli to bind human transferrin. AB - The gene for gonococcal transferrin-binding protein 1 (TBP1) was cloned behind an inducible promoter in Escherichia coli. The resultant strain was capable of binding human transferrin with the same specificity as that of the gonococcus. E. coli expressing TBP1 did not internalize transferrin-bound iron or grow on transferrin as a sole iron source. PMID- 8468303 TI - Role of the recA-related gene adjacent to the recA gene in Pseudomonas aeruginosa. AB - The region adjacent to the 3' end of the recA gene is indispensable for normal cell division in a rec-2 strain of Pseudomonas aeruginosa when the recA gene is highly expressed. A putative protein encoded by this region may play a regulatory role(s) in recA function. PMID- 8468304 TI - The Ada protein is a class I transcription factor of Escherichia coli. AB - The methylated Ada protein of Escherichia coli, a regulatory protein for the adaptive response, binds to a target DNA from positions -62 to -31 upstream of the ada gene and facilitates the binding of RNA polymerase to the promoter. Mutant RNA polymerases consisting of C-terminal-deleted alpha subunits are virtually inactive in response to activation by the Ada protein. Thus, we conclude that the Ada protein is a class I transcription factor which requires the C-terminal region of the RNA polymerase alpha subunit for transcription activation. PMID- 8468305 TI - The dilution rate affects the outer membrane protein and lipopolysaccharide composition of Haemophilus influenzae type b grown under iron limitation. AB - When Haemophilus influenzae type b was grown under iron limitation in continuous culture, the dilution rate affected the outer membrane protein and lipopolysaccharide composition. Investigations of the effect of the reduced availability of iron or other environmental parameters on these surface components should be controlled for growth rate. PMID- 8468306 TI - Effects of amino acid substitutions in the promoter -10 binding region of the sigma A factor on growth of Bacillus subtilis. AB - On the bases of structural and functional information about the Bacillus subtilis sigma A protein and the techniques of site-directed mutagenesis, we constructed a B. subtilis sigA mutant (DB1005) which grows normally at 37 degrees C but is sensitive to higher temperatures. DNA sequencing analyses revealed that DB1005 has Ile-198-->Ala and Ile-202-->Ala amino acid substitutions in the alpha-helix of the 2.4 region of the sigma A protein. Western blotting (immunoblotting) revealed that this mutant sigma A protein is stable at both 37 and 49 degrees C. These results suggest that Ile-198 and Ile-202 separately or in combination are critical for the sigma A protein to be functional at the restrictive temperature. PMID- 8468307 TI - Cloning and sequence determination of the valS gene, encoding valyl-tRNA synthetase in Lactobacillus casei. AB - The DNA sequence of the valS gene from Lactobacillus casei and the predicted amino acid sequence of its valyl-tRNA synthetase product have been determined. An open reading frame coding for a protein of 901 amino acids was found. A clone containing the intact L. casei valS gene functionally complemented the temperature-sensitive growth of the valS mutant strain 236c of Escherichia coli. The valS gene and the downstream folylpolyglutamate synthetase gene are transcribed in the same direction but are separated by a putative transcription terminator. PMID- 8468308 TI - Negative symptoms and emotional blunting in schizophrenic patients. AB - BACKGROUND: Emotional blunting and negative symptoms were explored as interchangeable concepts in evaluating schizophrenic patients. METHOD: We evaluated 115 consecutively admitted patients who had DSM-III-R schizophrenia. We performed a principal component analysis of Abrams and Taylor's Scale for Emotional Blunting (SEB) and Andreasen's Scale for the Assessment of Negative Symptoms (SANS) and correlated the subscales derived by factor analyses with demographic and clinical variables. RESULTS: Both scales contained subscales corresponding to poverty of affect and speech and inappropriate affect. The SEB also included an indifference subscale, whereas the SANS included avolition anhedonia, asociality, and blocking subscales. Poor premorbid functioning was most strongly associated with poverty of affect and speech. Inappropriate affect and anhedonia-avolition-asociality were moderately correlated with poor response to treatment. CONCLUSION: Negative symptoms and emotional blunting are similar concepts, but they are not interchangeable. Flatness and inappropriateness appear to be different affective dimensions with different clinical correlations. Inappropriate affect, inattention, and blocking should not be considered negative symptoms. PMID- 8468309 TI - Possible effects of smoke-free inpatient units on psychiatric diagnosis and treatment. AB - BACKGROUND: The author undertook to review the effects of abstinence from smoking and how those effects might influence the diagnosis and treatment of psychiatric disorders when patients are required to temporarily refrain from smoking (e.g., on inpatient wards) or when patients decide to stop smoking permanently. METHOD: Computerized data bases and reference lists of existing articles were searched for prior publications from three areas: (1) the association of smoking and psychiatric disorders, (2) the effects of nicotine withdrawal, and (3) the role of nicotine in psychiatric disorders. RESULTS: Withdrawal-induced increases in anxiety, depression, insomnia, irritability, restlessness, and weight and decreases in heart rate could affect the ability to evaluate alcohol/drug withdrawal, anxiety disorders, etc. Withdrawal effects could mimic medication side effects or increase the blood levels of several psychiatric medications. Whether these effects occur frequently or are of clinical magnitude has not been tested in studies of psychiatric patients. CONCLUSION: Psychiatrists should consider the effects of abstinence from smoking when diagnosing and treating patients who enter smoke-free inpatient units or who stop smoking during outpatient treatment. PMID- 8468311 TI - Ciprofloxacin-induced catatonia. PMID- 8468310 TI - Titration of serotonin reuptake blockers. PMID- 8468312 TI - Venlafaxine: a new dimension in antidepressant pharmacotherapy. PMID- 8468313 TI - Alcohol, drugs, and psychiatric comorbidity among homeless women: an epidemiologic study. AB - BACKGROUND: Very little is known about the mental health of homeless women. The present study is one of the first to focus on psychiatric diagnosis and comorbidity in a population of homeless women systematically interviewed with a structured instrument. METHOD: Three hundred homeless women randomly selected from St. Louis shelters were interviewed using the Diagnostic Interview Schedule (DIS). RESULTS: The population of homeless women in St. Louis is predominantly young adult, single, and black; most have young children and average nearly a high school education. Schizophrenia and bipolar affective disorder account for only a small portion of the mental illness in these women. Nearly one in three has a history of substance abuse, with drug abuse being more prevalent than alcoholism. One third of the sample met lifetime criteria for posttraumatic stress disorder. One fourth of the women have received inpatient psychiatric care, and the majority with a nonsubstance Axis I diagnosis have received some mental health treatment. CONCLUSION: Although major mental illness is overrepresented among these homeless women, the majority do not suffer from major mental illness. Despite the severity of the stressors these women face, the large numbers escaping psychiatric disorders speak to their resilience and to the likelihood that important factors other than mental illness contribute to their homelessness. Future studies to examine positive outcomes and investigate protective factors might provide a valuable source of information on coping with the stresses associated with homelessness and point to more effective interventions. PMID- 8468314 TI - Relationship of past depressive episodes to symptom severity and treatment response in panic disorder with agoraphobia. AB - BACKGROUND: Many investigators have reported that panic disorder (PD) patients with comorbid major depression (MD) have more severe symptoms and a poorer response to treatment than patients with PD alone. It is not known if this is due to a distinct and more serious underlying disorder in these patients or simply a result of the simultaneous presence of the two disorders. METHOD: Nondepressed patients presenting for treatment of panic disorder with agoraphobia (PDA) were studied before treatment (N = 180) and after 4 weeks of treatment with adinazolam sustained release (N = 89) or placebo (N = 91). Twenty-nine percent (N = 53) of the patients had a past history of MD. Symptom severity and treatment outcome were compared in patients with primary, secondary, single, recurrent, or no past MD. RESULTS: There were no consistent differences in symptom severity or treatment outcome in patients with a past history of primary, secondary, or single episode MD compared with patients with no history of MD. However, a small number of patients with history of recurrent MD exhibited consistently greater symptom severity and poorer response to treatment than patients with no history of MD. CONCLUSION: The greater severity and worse outcome of comorbid PD and MD observed in earlier studies are more likely due to the simultaneous presence of the two disorders than to a more serious and enduring underlying disorder. However, our results suggest that recurrent MD may indicate a more serious condition in patients with PDA. This possibility warrants further study. PMID- 8468315 TI - Direct demonstration of the essential role of the intramolecular high-mannose oligosaccharide chains in the folding and assembly of soybean (glycine max) lectin polypeptides. AB - We investigated the role of the intramolecular high-mannose oligosaccharide chains in the folding and assembly of soybean lectin polypeptides. Soybean lectin, dissociated into subunits and completely denatured in 6 M guanidine hydrochloride, was quantitatively reconstituted to the active tetrameric structure by simple dilution. However, neither the activity nor the tetrameric structure was regained in the presence of 100 microM of an asparagine-linked oligosaccharide, Man9GlcNAc2Asn, having the same structure as that of the sugar chains of soybean lectin. Besides, the same concentration of this glycopeptide even dissociated, although only gradually, the native lectin into subunits. On the other hand, the deglycosylated subunits had no ability to regain the activity or the tetrameric structure. The present study provided for the first time direct evidence of the essential role of the intramolecular high-mannose oligosaccharide chains in the proper folding and assembly of glycopolypeptides. PMID- 8468316 TI - Identification of the specific labile sites in the 180 kDa catalytic polypeptide of the Drosophila melanogaster DNA polymerase alpha-primase complex. AB - The immunoaffinity-purified DNA polymerase alpha-primase complex from Drosophila melanogaster Kc cells contains three high molecular weight polypeptides besides the 180 kDa catalytic polypeptide. These polypeptides are immunologically cross reactive with the 180 kDa polypeptide. When the immunoaffinity-purified complex was kept at 4 degrees C for about four weeks, the amounts of the three polypeptides increased, while the 180 kDa polypeptide completely disappeared. Sodium bisulfite inhibited the decrease in the 180 kDa polypeptide. The N terminal amino acid sequences of all the polypeptides were all assigned to ones present in a portion close to the N-terminus of the 180 kDa polypeptide. The N terminal residue of all the three polypeptides was Ser. The cleavage sites were Phe130-Ser131, Thr180-Ser181, and Phe237-Ser238. These results show that the three polypeptides are cleavage products of the 180 kDa catalytic polypeptide, the cleavage occurring at specific labile sites including a Ser residue. The amino acid residues at the sites are quite different from those (Lys-Lys) in the human 180 kDa catalytic polypeptide. PMID- 8468317 TI - Examination of processing of the rat liver mitochondrial F1-ATPase beta subunit precursor protein by high-resolution 2D-gel electrophoresis. AB - We report the one-step processing of the rat liver beta-F1-ATPase precursor protein, as examined by high resolution 2D-gel electrophoresis. Proteolytic cleavage of the positively charged mitochondrial targeting signal of the precursor promotes decreases in both the molecular weight (approximately 3 kDa) and the isoelectric point (approximate 0.2 pH unit) of the protein. The results obtained illustrate the usefulness of this technique, since it takes advantage of both results of the maturation process, for molecular characterization of the processing of mitochondrial precursor proteins. PMID- 8468318 TI - Identification and functional expression of a new member of the mammalian Kex2 like processing endoprotease family: its striking structural similarity to PACE4. AB - We used the polymerase chain reaction to identify a mouse cDNA which represented a new member of a growing class of mammalian endoproteases homologous to the yeast Kex2 protease involved in the processing of precursor proteins. This cDNA encoded a 915-residue protein, designated as PC6, containing a subtilisin-like catalytic domain closely related to those of other Kex2-like members (furin, PC2, PC1/3, PC4, and PACE4). It exhibited striking sequence similarity to PACE4 and contained similar protein domains, such as the COOH-terminal Cys-rich region. Northern blot analysis revealed that PC6 mRNA, as with furin and PACE4 mRNAs, was expressed in various tissues and cell lines, with the highest level in the intestine. Transfection experiments revealed that PC6 was capable of cleaving precursors at dibasic sites. These observations suggest that PC6 is a candidate for a processing endoprotease responsible for the maturation of gastrointestinal peptides. PMID- 8468319 TI - Stereochemistry of intermediates in the conversion of 3 alpha,7 alpha,12 alpha trihydroxy-5 beta-cholestanoic acid to cholic acid by rat liver peroxisomes. AB - We have investigated the stereochemistry of the side chain of the intermediates, 3 alpha, 7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid and 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid, in the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid by rat liver peroxisomes. The intermediates formed were converted to the p-bromophenacyl ester derivatives and analyzed by reversed-phase high-performance liquid chromatography. Only the (24E) form of the two isomers of the delta 24 unsaturated acid and the (24R,25S) form of the four isomers at C-24 and C-25 of the 24-hydroxy acid were found to be formed stereospecifically from either (25R)- or (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. Formation of the other isomers of the alpha beta-unsaturated bile acid or the beta-hydroxy bile acid was not detected. The findings support the proposed pathway for the side-chain cleavage in cholic acid biosynthesis, which is thought to be similar to that of peroxisomal fatty acid beta-oxidation. PMID- 8468321 TI - cDNA and genomic structures of arrowhead proteinase inhibitors. AB - Arrowhead double-headed proteinase inhibitors A and B consist of 150 amino acid residues with three disulfide bonds. Based on their primary structures, three cDNA fragments of the inhibitors were amplified in vitro by the PCR method using a constructed arrowhead cDNA library as a template. With the overlapping sequences, the full-length cDNA sequences of the inhibitors were then ascertained. The open reading frame encodes a pre-inhibitor, including a 24 residue signal peptide. The deduced amino acid sequences are consistent in principle with those determined by primary structure analysis, except that there are seven extra residues in the C-terminal part of the inhibitors, which might be cleaved off by proteinase post-processing immediately after protein synthesis. It is worth pointing out that cDNAs of both inhibitors A and B contain an 87 bp intron in the AAG codon of residue Lys-97. According to the elucidated cDNA sequences, the structural genes of inhibitors A and B were amplified using the total cDNA or genomic DNA of arrowhead as a PCR template. It was indicated that both the cDNA and genomic structures of inhibitors A and B have the same sequences. PMID- 8468320 TI - Three forms of rat CYP11B genes: 11 beta-hydroxylase gene, aldosterone synthase gene, and a novel gene. AB - We isolated three genomic clones of rat P-450(11 beta) genes (CYP11B). Two of them corresponded to 11 beta-hydroxylase gene (CYP11B1) and aldosterone synthase gene (CYP11B2), respectively. The third one was a novel gene resembling both CYP11B1 and CYP11B2, and was named CYP11B3 gene (CYP11B3). CYP11B2 and CYP11B3 are located tandemly in the genome in the same direction approximately 24 kb apart. These three genes were highly homologous in their amino acid coding regions, with 88% (CYP11B1 to CYP11B2), 89% (CYP11B2 to CYP11B3), 96% (CYP11B1 to CYP11B3) nucleotide identity. The numbers and the locations of the exons of these three genes also exactly corresponded to each other. However, the nucleotide sequences of the 5' upstream regions of CYP11B1 and CYP11B2 were significantly different, suggesting different transcriptional regulations. CYP11B3 had almost the same sequence as CYP11B1 gene in the 5' upstream region. A putative Ad4 site, a cis-acting element present in the promoter regions of all the steroidogenic P 450s so far reported [Morohashi, K., Honda, S., Inomata, Y., Handa, H., Omura, T. (1992) J. Biol. Chem. 267, 17913-17919], was found in the promoter regions of both CYP11B1 and CYP11B2. Gel retardation analysis showed the binding of Ad4BP purified from bovine adrenal cortex to these two Ad4 sites. We analyzed the relative abundance of the mRNAs corresponding to these three genes by the generation of RT-PCR libraries from rat adrenal total RNAs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468322 TI - Arrangement of the disulfide bridges in a blood coagulation factor IX/factor X binding protein from the venom of Trimeresurus flavoviridis. AB - Blood coagulation factor IX/factor X-binding protein (IX/X-bp) is a two-chain anticoagulant protein that was isolated from the venom of Trimeresurus flavoviridis. The amino acid sequence of IX/X-bp is homologous to the sequences of C-type lectin-like proteins, such as asialoglycoprotein receptor, tetranectin, and the low-affinity Fc epsilon receptor of immunoglobulin E. The amino acid composition and amino acid sequence of cystine-containing peptides, formed as a result of enzymatic digestion of CNBr-generated fragments of IX/X-bp, were analyzed to determine the location of the seven disulfide bridges in the protein. Three disulfide bridges in the A chain link Cys2 to Cys13, Cys30 to Cys127, and Cys102 to Cys119. Three disulfide bridges in the A chain link Cys2 to Cys13, Cys30 to Cys119, and Cys96 to Cys111. An interchain disulfide bond links Cys79 of the A chain and Cys75 of the B chain. The intrachain disulfide-bonding patterns of both the A and B chains of IX/X-bp are similar to those found in other C-type lectin-like proteins. We discuss in this report the sequence homology between IX/X-bp and other two-chain, C-type lectin-like proteins that have been isolated from snake venoms and we compare the S-S bonding patterns of proteins that are homologous to IX/X-bp. PMID- 8468323 TI - A complementary DNA for an ascidian embryonic nuclear antigen Hgv2 encodes a protein closely related to the amphibian histone-binding protein N1. AB - We have isolated and sequenced a cDNA clone encoding an ascidian embryonic nuclear protein, Hgv2. An insert about 2 kb long covered almost the entire length of 2.3-kb Hgv2 mRNA. The amino acid sequence of Hgv2 deduced from the cDNA sequence showed that this protein is related to the amphibian karyophilic histone binding protein N1, which is thought to be involved in nucleosome assembly. Homology between these two proteins is evident from their extremely similar amino acid compositions and hydropathy profiles. In addition, Hgv2 protein has sequences strikingly similar to the nuclear targeting signal of N1. This is therefore the first report of molecular cloning of a homologue of N1 in non amphibian species. Putative histone-binding domains of N1 are composed of two acidic residue-rich clusters. Hgv2 polypeptide contains two highly acidic regions, but amino acid sequences of the regions are not conserved. Since Hgv2 protein exists in nuclei of every embryonic cell but disappears from nuclei of metamorphosed juvenile tissues, this protein may function as a nucleosome assembly factor during rapid embryonic cell divisions. PMID- 8468324 TI - Fluorescent molecular rotor binding to actin. AB - 1-(2-Hydroxyethyl)-6-[(2,2-dicyano)vinyl]-2,3,4-trihydroquinoli ne (DCQ) is a fluorescent dye and its fluorescence yield is determined by a freedom of intramolecular rotation. When DCQ was added to an actin solution, its fluorescence intensity increased as the actin molecule transformed from G-actin to F-actin. This fluorescence intensity increase was induced both by the higher binding constant of the dye to F-actin than to G-actin and by the higher fluorescence yield of the dye bound to F-actin than to G-actin. DCQ bound more strongly to Mg(2+)-F-actin than to Ca(2+)-F-actin, resulting in higher fluorescence intensity of DCQ-Mg(2+)-F-actin solution than of DCQ-Ca(2+)-F-actin solution. DCQ did not distinguish Mg(2+)-G-actin and Ca(2+)-G-actin. Thus, DCQ is a good probe for polymerization of actin and polymorphism of F-actin. PMID- 8468325 TI - Tissue-specific and developmentally regulated expression of the genes encoding adenylate kinase isozymes. AB - Adenylate kinase (AK) is known to play an important role in homeostasis of adenine nucleotide metabolism. We isolated cDNAs for rat AK isozymes (AK1, AK2, and AK3), determined their mRNAs in rat tissues by Northern blot analysis, and measured the isozyme activities. Tissue-dependent activities of AK1 and AK2 paralleled the contents of mRNAs. Tissues with high AK1 levels showed low AK2 levels and vice versa, suggesting that tissue-specific expressions of the AK1 and AK2 genes are inversely regulated. AK3 mRNA was detected in most tissues examined, suggesting that AK3 gene expression is constitutive. We further examined developmental changes in mRNAs and enzyme activities of AK isozymes in rat skeletal muscle and liver. In the skeletal muscle, AK1 and AK3 activities started to increase at around the weaning period. AK1 mRNA accumulated at the prenatal stage and further increased during development, while AK3 mRNA was at high levels during the fetal stage and remained fairly constant during development. In the liver, AK2 and AK3 activities started to increase after birth and were further elevated during growth, whereas their mRNAs were present at relatively high levels throughout development. The physiological meanings of the tissue-specific expression of the AK isozyme genes are discussed. PMID- 8468326 TI - Inhibition of aspartate chemotaxis of Escherichia coli by site-directed sulfhydryl modification of the receptor. AB - Thr-154 of the chemoreceptor Tar in Escherichia coli is important for aspartate sensing. Taking advantage of the fact that Tar has no Cys residues, we have further investigated the role of Thr-154 by replacing it with Cys in order to subject it to SH modification. Tar-T154C retained the abilities of aspartate sensing and repellent sensing. However, when cells with Tar-T154C were treated with an SH-modifying reagent, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB), they specifically lost the ability to sense aspartate; the ability was restored by the reducing reagent, 1,4-dithiothreitol. DTNB showed no detectable effect on the function of wild-type Tar or serine-replaced Tar, Tar-T154S. Thus, DTNB modifies Cys-154 of Tar-T154C in intact cells and causes a specific defect in the aspartate-sensing ability of Tar. The addition of 1 mM or higher concentrations of aspartate resulted in protection of Cys-154 from the modification; serine had no effect in this regard. These results that not only is Thr-154 important for aspartate sensing but also, it may be located at the actual aspartate-binding site. PMID- 8468327 TI - Functional analysis of cDNAs for two types of human heme oxygenase and evidence for their separate regulation. AB - We cloned a cDNA coding for a putative human heme oxygenase isozyme, designated type 2 (HO-2), and analyzed its function by transient expression assays. HeLa cells transfected with either HO-2 cDNAs or a cDNA coding for authentic heme oxygenase (HO-1) expressed the activity of heme oxygenase, although no activity was detected in the mock transfected cells. Using specific anti-HO-1 antibody, we showed that expression of a HO-1 cDNA resulted in the increase in its protein levels, but HO-1 protein was not detectable in the cells expressing HO-2 cDNAs. We thus confirmed the functional identity of HO-1 and HO-2. Then, we analyzed their expression in an erythroid cell line, YN-1-0-A. Treatment with hemin or by heat shock (42 degrees C) led to a remarkable increase in the HO-1 mRNA levels, while HO-2 mRNA expression was not induced at all, suggesting that they are under separate regulation. PMID- 8468328 TI - Cleavage specificity and inhibition profile of proteasome isolated from the cytosol of Xenopus oocyte. AB - The specificity of action of the proteasome purified from the cytosol of Xenopus oocyte was investigated using oxidized insulin B chain as the substrate. HPLC analyses of the produced peptides followed by amino acid analyses showed that it cleaved four peptide bonds, Leu6-Cya7, Glu13-Ala14, Leu15-Tyr16, and Leu17-Val18, of the peptide. Cleavage at Leu6-Cya7 was found to be specific to the Xenopus enzyme. The enzyme did not cleave Gln4-His5 and Cya19-Gly20, which are commonly hydrolyzed by proteasomes from rat and mouse liver, and human erythrocyte. In contrast to previous results obtained with the mammalian proteasome, the cleavage by the Xenopus enzyme was inhibited selectively by chymostatin. These results demonstrate distinct species difference in cleavage specificity and inhibition profile among proteasomes of different origins. PMID- 8468329 TI - Purification and characterization of two isoforms of serine proteinase from the microsomal membranes of rat liver. AB - An extensive purification of microsomal serine proteinase was achieved from rat liver microsome membranes solubilized with 1% sodium cholate by a series of column chromatographic steps on hydroxylapatite, DEAE-cellulose, and benzamidine Sepharose 6B, and polyacrylamide gel electrophoresis (PAGE). In the final step of PAGE, the enzyme was separated into two fractions with slightly different mobilities, designated microsomal serine proteinases 1 (MSP1) and 2 (MSP2). The former was purified about 8,000-fold to apparent homogeneity, and the latter was purified about 800-fold, starting from the sample which had been spontaneously activated after elution from the hydroxylapatite column. Both enzyme fractions showed essentially the same properties, including molecular weight, susceptibility to various proteinase inhibitors and metal ions, specificity of action toward protein substrates with special preference for a basic protein histone as well as toward synthetic substrates, and pH dependence of activity toward a synthetic substrate and two neuropeptides. Taken together with the same behavior on a series of chromatographic steps, the two isoforms are thought to be essentially the same enzyme. Further, the detailed kinetic studies of the enzyme activity, especially of MSP1, toward various synthetic and naturally occurring peptide substrates showed that it was highly specific for basic amino acid pairs, strictly hydrolyzing at the COOH side of arginine residue. These results are consistent with those obtained previously with a partially purified enzyme and establish more definitely and in detail the specificity as well as other molecular and enzymatic properties of the enzyme. PMID- 8468331 TI - Antibodies raised against the adenosine receptor agonist, 5'-N ethylcarboxamidoadenosine (NECA). AB - Antisera against the non-selective adenosine receptor agonist 5'-N ethylcarboxamido-adenosine (NECA) have been raised by immunizing rabbits with NECA-coupled bovine serum albumin. The antisera which bind [3H]NECA with high affinity were purified by affinity chromatography using NECA-coupled Sepharose as the affinity gel without significant changes in [3H]NECA-binding properties. The order of the affinity for various adenosine receptor ligands of the purified or unpurified antisera was 5'-N-cyclopropylcarboxamidoadenosine > or = NECA > 2',5' dideoxyadenosine > 2-chloroadenosine > theophylline > isobutylmethylxanthine > (R)-N6-phenylisopropyladenosine = N6-cyclohexyl- adenosine. This specificity was found to be similar to that of the non-receptor NECA-binding sites, which had been found in various tissues such as human placentas and mouse P815 mastocytoma cells, rather than to that of adenosine receptors. These anti-NECA antibodies will be useful as immunochemical agents in the search for endogenous ligand(s) to the non-receptor NECA-binding sites. PMID- 8468330 TI - Isolation of N omega-phosphoarginine hydrolase from rat liver and its physical properties. AB - N omega-Phosphoarginine hydrolase from rat liver cytosol was purified to apparent homogeneity on SDS-PAGE, by employing column chromatographies on Sephadex G-75, DEAE-cellulose, QAE-Toyopearl, and glutathione-2-pyridyl-disulfide-Superose. One milligram protein of the final preparation released 4 mumol/min of inorganic phosphate from N omega-phosphoarginine. The molecular mass on SDS-PAGE, the Stokes' radius and the sedimentation coefficient were estimated to be 17.3 kDa, 1.63 nm, and 2.0 s, respectively, indicating that this enzyme consists of a single peptide. The stability of the enzyme to heat depended on the buffers employed and treatment of the enzyme preparation in 50 mM Tris-HCl, pH 7.0 at 50 degrees C, reduced the hydrolytic activity with a decay constant of 0.099 per min. PMID- 8468332 TI - Ganglioside distribution in the liver of inbred strains of rats and the cancerous liver of LEC rats. AB - The gangliosides in the livers of various inbred strains of rats and hepatoma of LEC rats were purified and analyzed by thin-layer chromatography. The patterns of ganglioside distribution in these rat livers were classified into three phenotypes depending on the strain, that is, a-type (ACI, LEA, LEW, BUF), b-type (WKAH, SHR/SP), and LEC type, which are characterized by dominance of a- or b series of gangliosides, or a variation of a-type, respectively. A sex difference was also recognized in the molar ratio of GM3 which was much higher in males (60 75%) than in females (33-56%) except in LEC rats. In addition, the content of a series gangliosides was lower and the content of b-series gangliosides was higher in a-type male rats than in a-type female rats. The opposite was true in b-type rats. LEC rats were an exception, characterized by no sex difference and a quite low content of b-series gangliosides. The LEC rat is a mutant strain that spontaneously develops fulminant hepatitis around 14 to 20 weeks of age and hepatoma at 1 to 1.5 years old. The gangliosides of the hepatoma were characterized by the appearance of the newly synthesized gangliosides, fucosyl GM1 and alpha-galactosyl alpha-fucosyl GM1 (BGM1). In particular, BGM1 ganglioside accumulated in the hepatoma of female rats. PMID- 8468333 TI - The complete amino acid sequence of a Kunitz family trypsin inhibitor from seeds of Acacia confusa. AB - The complete amino acid sequence of a Kunitz-type two-chain trypsin inhibitor was determined for the first time. The sequence of the inhibitor from Acacia confusa (ACTI) was determined by analysis of peptides obtained from the reduced and S carboxymethylated protein by digestion with endopeptidase Lys-C, endopeptidase Arg-C, and V8 endopeptidase. ACTI is comprised of two chains, namely A and B chains linked by the disulfide bridge between Cys(133) and Cys(141), and the inhibitor consists of 175 amino acid residues, 136 residues in the A-chain and 39 residues in the B-chain. The N-terminal amino acid sequence of ACTI shows extensive homology to the trypsin inhibitors from Acacia elata and Albizzia julibrissin, while the whole amino acid sequence of ACTI has a high degree of homology to the other Kunitz-type trypsin inhibitors from soybeans, winged bean seeds [Psophocarpus tetragonolobus (L) DC.], and seeds of Erythrina species. PMID- 8468334 TI - Hydrolysis of cholesteryl oleate liquid crystals by hormone-sensitive lipase. AB - Cholesteryl oleate liquid crystals were prepared by sonication as a model of lipid droplets accumulated in foam cells derived from macrophages. These liquid crystals were spherical and showed an anisotropic cross image. Hormone-sensitive lipase from bovine adipose tissue hydrolyzed these liquid crystals optimally at pH 6.8. The Km for the liquid crystals was about 8 times that for vesicles or emulsified cholesteryl oleate. The Vmax for the liquid crystals was the same as that for the emulsified substrate and 6 times that for the vesicle substrate. Phospholipid inhibited cholesteryl oleate hydrolysis in a concentration-dependent fashion, phosphatidylserine being especially inhibitory. The effect of phospholipids on the activity changed upon their incorporation into the cholesteryl oleate liquid crystals, phosphatidylethanolamine increasing the activity to about twice that of the control. These results suggest that hormone sensitive lipase hydrolyzes cholesteryl oleate liquid crystals as a model of endogenous lipid droplets and its activities are affected by phospholipids. PMID- 8468336 TI - A method for measuring mechanical work and work efficiency during human activities. AB - A major limitation in understanding human energy balance is the ability to accurately quantify the amount of physical activity or work performed by human subjects. We describe the development and validation of a force platform (2.5 x 2.5 m) system for measuring external mechanical work performed by human subjects. The force platform system was constructed inside a whole-room indirect calorimeter, thus, allowing simultaneous measurement of the energy expenditure associated with physical activity. We demonstrated the accuracy of the system for measuring work performed using a solenoid (32 kg) to deliver controlled amounts of energy to the platform. In tests with human subjects we demonstrated that the system can accurately and reproducibly measure work performed, energy expenditure associated with work performed, and work efficiency (work performed divided by energy expenditure). Overall, we obtained high correlations (an average of 0.932 for 33 subjects), between mechanical work performed and energy expenditure. We believe this mechanical work-energy expenditure system will be useful in determining the importance of individual differences in amount and cost of physical activity in the regulation of body weight and in development of obesity. PMID- 8468335 TI - The effect of temperature, stress and microstructure on the creep of compact bovine bone. AB - Creep tests of 117 compact bovine bone specimens were conducted at three temperatures (25, 37, and 43 degrees C), with applied stresses between 71 and 115 MPa. Following testing, the amount of secondary haversian bone in the gage region of the specimens was estimated. The resulting steady-state creep rates (epsilon) were fit to an Arrhenius (e-Qc/RT) model (where Qc is the activation energy for the mechanism(s) controlling creep, R is the gas constant, and T is the absolute temperature) of the type used to describe the classic steady-state creep behavior of metals, ceramics, and metamorphic rocks. The empirical model developed was epsilon = 5.6 x 10(-9) e4.6F sigma 5.2 e-5330/T, where epsilon is the estimated mean steady-state creep rate, F is the volume fraction of secondary haversian bone, sigma is the applied stress, and T is the absolute temperature. There was a positive, significant association between the estimated mean steady-state creep rate and F, sigma, and T. Qc was determined to be 44.3 kJ mol-1, a reasonable value when compared to activation energies for creep in ceramics. It is hypothesized that permanent deformation during creep of compact bovine bone is primarily due to damage mechanisms associated with dislocations in the hydroxyapatite mineral lattice structure. PMID- 8468337 TI - Kinematics of jaw movements during chewing at different frequencies. AB - The three-dimensional jaw movement trajectory and its velocity profile were investigated to provide information regarding the motor control of chewing. This was done on a cycle-by-cycle basis across three voluntarily guided chewing frequencies to test the lack of invariance at the velocity level and the evidence for a cost function. The data revealed that an increase in chewing frequencies resulted in a significant reduction of the three-dimensional path, being significantly higher in opening than closing. The ratio of peak speed/three dimensional distance, a kinematic index of stiffness, increased with increase in chewing frequency; higher stiffness being associated with faster chewing, the stiffness being significantly higher in opening than in closing. The ratio of peak velocity to mean velocity decreased as a function of increase in chewing frequency only at the highest frequency and this decrease again was different in opening than in closing. The results demonstrated that the velocity profile of chewing movements, like that of speech movements, lacked invariance. Rather than minimizing one cost function, the system used an efficient trade-off between time, space and effort, based on the objective of movements. PMID- 8468338 TI - Evaluation of finite element analysis for prediction of the strength reduction due to metastatic lesions in the femoral neck. AB - Between 30 and 70% of almost one million new cancer patients diagnosed each year will develop osseous metastases. Clinicians are faced with the difficult task of determining which patients require prophylactic stabilization to prevent pathologic fracture. The objective of this study was to test the ability of macroscopic finite element models to predict the fracture strength of the proximal femur with a lesion in the femoral neck. Drill hole defects in human cadaver femora were used to simulate lesions that penetrate one cortex of the femoral neck. Based on the first of two series of in vitro experiments, the fracture strength of a femur with a lesion that penetrates either the inferior medial or superior-lateral cortex of the neck is approximately 45% less than the fracture strength of the paired intact femur; based on the second series, the fracture strength with the inferior-medial lesion is approximately 20% less than the fracture strength with the superior-lateral lesion. A series of three dimensional finite element models were used to predict the fracture strength for anterior and posterior lesions, as well as the inferior-medial and posterior lateral lesions tested in vitro. Based on a direct comparison of the strengths predicted by the finite element models to the measured in vitro fracture strengths, the finite element models performed poorly. In particular, the application of an anisotropic strength criterion to the stresses predicted by the models resulted in a considerable underestimation of the percentage reduction in the in vitro fracture strength. This may reflect a fundamental inability of a linear, macroscopic continuum-based analysis to predict accurately the fracture strength of a bone structure as complex as the proximal femur. However, despite this lack of agreement in absolute fracture strength, the general trends for gait and stair ascent loading for the inferior-medial and superior-lateral lesions were consistent with the in vitro data. The greatest reduction in strength was predicted for the inferior-medial lesion, followed by the anterior lesion and then the superior-lateral lesion, and the least reduction in strength was predicted for the posterior lesion. Most importantly, the predicted strength ratio varied considerably as a function of the applied loads. Any metastatic lesions of the femoral neck may be especially sensitive to some particular activity, making it difficult to determine precisely the risk of fracture. PMID- 8468339 TI - Absolute angle measurement using the earth-field-referenced hall effect sensors. AB - A miniaturized absolute angle sensor utilizing Hall generators referenced to the Earth's ambient magnetic field has been developed. The sensor has three dimensional angular sensitivity which allows the output to be self-normalized resulting in high immunity to both B-field and temperature induced errors. The individual Hall generator elements were operated with a final sensitivity of 4.07 V G-1. The Earth's field, magnitude 0.486 G with a surface declination angle of 58.2 degrees (San Diego, California), was used as the excitation/reference field. Bandwidth limiting, low-noise design, and active/passive thermal compensation techniques were employed resulting in a sensor bandwidth of DC to 100 Hz with a maximum signal-to-noise ratio of 44.5 dB. The maximum angular resolution of the sensor was measured to be +/- 0.27 degrees. Temperature induced error was measured to be less than 2% from 25 degrees C to 40 degrees C. The measurement of shoulder joint rotation was used as the test case application for the sensor with excellent agreement between theoretical and experimental performance. PMID- 8468340 TI - A technique for the tensile testing of demineralised bone. AB - The purpose of this study was to devise a method for the tensile testing of the organic component of demineralised bone. It was hoped that the method could be applied to determine whether an observed reduction in the strength of bone in copper-deficient rats could be attributed to a reduction in the cross-linking of collagen. Tensile testing of a fully demineralised specimen proved impossible to perform because of the difficulty in gripping the material, which tended to slide out of its holding clamps. The technique devised involved the demineralisation of only the diaphysis of the bone, leaving the bone ends intact. This enabled the bone to be gripped firmly at both ends in an Instron tensile testing machine. Elongation under loading of the demineralised diaphysis was measured by the Instron and a video recording was made of the elongation of the central portion. The strain was found to be uniform. Tensile strength was found to correlate with copper levels in the liver (r = 0.54, p < 0.05), although no significant differences were found between the strength, the stiffness, or the strain to failure for bone from the copper-deficient animals and bone from the normal controls. The test method itself should be useful in other studies in which the tensile properties of the organic phase of bone need to be measured. PMID- 8468341 TI - A static dynamometer measuring multidirectional torques exerted simultaneously at the hip and knee. AB - The function of a static dynamometer measuring torques exerted simultaneously in the different anatomical planes of the hip (flexion-extension, abduction adduction and internal-external rotation) and knee (flexion-extension) is described. Muscular torques were calculated in real time using a desktop computer from measurements of orthogonal forces applied at two locations and the lever arm values measured in each subject. The reliability of the force transducers was explored by examining their output, using calibrated weights, on three different days. The results were identical over this period of time, indicating that the transducers are highly reliable. A mechanical simulator of a lower limb was constructed to generate specific or combined torques of known values at the hip and knee. The torques measured by the dynamometer were found to be highly concordant with the known torques applied by the simulator, indicating that the torque measurements were valid. The usefulness of the dynamometer is demonstrated by evaluating the activity of the rectus femoris and biceps femoris muscles during static efforts exerted in various directions at the hip. In addition, the mechanical action of biarticular muscles at the hip was evaluated by quantification of hip torques during efforts exerted at the knee. From these results, it has been concluded that the present biarticular and multidirectional dynamometer is a valid, reliable and precise instrument that may prove to be useful in evaluating the muscular function of the lower limb. PMID- 8468342 TI - Abstracts of NACOB II. The 2nd North American Congress on Biomechanics. PMID- 8468343 TI - Association of individual hnRNP proteins and snRNPs with nascent transcripts. AB - As they are transcribed, RNA polymerase II transcripts (hnRNAs or pre-mRNAs) associate with hnRNP proteins and snRNP particles, and the processing of pre-mRNA occurs within these ribonucleoprotein complexes. To better understand the relationship between hnRNP proteins and snRNP particles and their roles in mRNA formation, we have visualized them as they associate with nascent transcripts on the polytene chromosomes of Drosophila melanogaster salivary glands. Simultaneous pairwise detection of the abundant hnRNP proteins hrp36, hrp40, and hrp48 by direct double-label immunofluorescence microscopy reveals all of these proteins are bound to most transcripts, but their relative amounts on different transcripts are not fixed. Numerous differences in the relative amounts of snRNP particles and hnRNP proteins on nascent transcripts are also observed. These observations directly demonstrate that individual hnRNP proteins and snRNP particles are differentially associated with nascent transcripts and suggest that different pre-mRNAs bind different combinations of these factors to form transcript-specific, rather than a single type of, hnRNA-hnRNP-snRNP complexes. The distinct and specific constellation of hnRNP proteins and snRNP particles that assembles on different pre-mRNAs is likely to affect the fate and pathway of processing of these transcripts. PMID- 8468344 TI - A cytoplasmically anchored nuclear protein interferes specifically with the import of nuclear proteins but not U1 snRNA. AB - A cytoplasmically anchored mutant SV40 T antigen, FS T antigen, was shown previously to interfere specifically with the nuclear import of a heterologous nuclear protein, adenovirus 5 fiber protein, in cultured monkey cells (Schneider, J., C. Schindewolf, K. van Zee, and E. Fanning. 1988. Cell. 54:117-125; van Zee, K., F. Appel, and E. Fanning. 1991. Mol. Cell. Biol. 11:5137-5146). In this report, we demonstrate that FS T antigen also interferes with the nuclear import of adenovirus E1A and a peptide-albumin conjugate bearing multiple copies of the T antigen nuclear localization signal, but not with the import of U1 snRNA. A kinetic analysis indicates that nuclear import of the albumin-peptide conjugate is inhibited only when high intracellular concentrations of FS T antigen are reached. After microinjection into the cytoplasm of cultured cells, purified FS T antigen protein does not accumulate at the nuclear periphery, but rather is distributed in a punctate pattern throughout the cytoplasm. These data support a model in which cytoplasmic anchoring of FS T antigen enables the mutant protein to sequester and titrate out a cellular factor which is required for nuclear protein but not U1 snRNA import. PMID- 8468345 TI - Unusual nuclear structures in meiotic prophase of fission yeast: a cytological analysis. AB - Earlier results from sectioned nuclei indicating that Schizosaccharomyces pombe does not develop a classical tripartite synaptonemal complex (SC) during meiotic prophase are confirmed by spreading of whole nuclei. The linear elements appearing during prophase I resemble the axial cores (SC precursors) of other organisms. The number of linear elements in haploid, diploid, and tetraploid strains is always higher than the chromosome number, implying that they are not formed continuously along the chromosomes. Time course experiments reveal that the elements appear after DNA replication and form networks and bundles. Later they separate and approximately 24 individual elements with a total length of 34 microns are observed before degradation and meiotic divisions. Parallel staining of DNA reveals changes in nuclear shape during meiotic prophase. Strains with a mei4 mutation are blocked at a late prophase stage. In serial sections we additionally observed a constant arrangement of the spindle pole body, the nucleolus, and the presumptive centromere cluster. Thus, S. pombe manages to recombine and segregate its chromosomes without SC. This might correlate with the absence of crossover interference. We propose a mechanism for chromosome pairing with initial recognition of the homologs at the centromeres and suggest functions of the linear elements in preparation of the chromosomes for meiosis I disjunction. With the spreading technique combined genetic, molecular, and cytological approaches become feasible in S. pombe. This provides an opportunity to study essential meiotic functions in the absence of SCs which may help to clarify the significance of the SC and its components for meiotic chromosome structure and function. PMID- 8468346 TI - A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau. AB - We previously reported the presence of the microtubule-associated protein, tau in the nuclei of primate cells in culture. The present study confirms the existence of nuclear tau in two human neuroblastoma cells lines by indirect immunofluorescence and Western blot using mAbs to tau. Northern blot analysis of poly A+ mRNA detects a novel 2-kb tau transcript coexpressed with the 6-kb message in cultured human cells and human frontal cortex. PCR and cDNA sequencing demonstrate that the 2-kb message contains the entire tau coding region. Furthermore, actinomycin D transcription inhibition experiments indicate that the 2-kb message is not derived from the 6-kb message, but instead arises from the original tau transcript. One of the human neuroblastoma cell lines examined contains both nuclear and cytoplasmic tau as assayed by both Western blot and indirect immunofluorescence. Northern blot analysis of this cell line indicates that copious amounts of the 2-kb message are present while little of the 6-kb transcript is obvious. Immunofluorescence analysis of this cell line demonstrates that the cytoplasmic tau is not localized to microtubules. Together, these results indicate that the 2-kb tau message in humans may specify tau for non microtubule functions in both the cytoplasm and the nucleus. We hypothesize that this is accomplished via a message targeting mechanism mediated by the untranslated regions of the tau messages. PMID- 8468347 TI - The rubella virus E2 and E1 spike glycoproteins are targeted to the Golgi complex. AB - Rubella virus (RV) has been reported to bud from intracellular membranes in certain cell types. In this study the intracellular site of targeting of RV envelope E2 and E1 glycoproteins has been investigated in three different cell types (CHO, BHK-21 and Vero cells) transfected with a cDNA encoding the two glycoproteins. By indirect immunofluorescence, E2 and E1 were localized to the Golgi region of all three cell types, and their distribution was disrupted by treatment with BFA or nocodazole. Immunogold labeling demonstrated that E2 and E1 were localized to Golgi cisternae and indicated that the glycoproteins were distributed across the Golgi stack. Analysis of immunoprecipitates obtained from stably transfected CHO cells revealed that E2 and E1 become endo H resistant and undergo sialylation without being transported to the cell surface. Transport of RV glycoproteins to the Golgi complex was relatively slow (t1/2 = 60-90 min). Coprecipitation experiments indicated that E2 and E1 form a heterodimer in the RER. E1 was found to fold much more slowly than E2, suggesting that the delay in transport of the heterodimer to the Golgi may be due to the slow maturation of E1 in the ER. These results indicate that RV glycoproteins behave as integral membrane proteins of the Golgi complex and thus provide a useful model to study targeting and turnover of type I membrane proteins in this organelle. PMID- 8468348 TI - Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway. AB - Amyloid precursor protein (APP) secretase plays a pivotal role in the processing of APP since its activity precludes the formation of amyloid peptide in Alzheimer's Disease. The identity and the subcellular localization of this enzyme are at this moment unknown. It is also unclear how APP escapes the activity of this enzyme when amyloid is formed. We have previously shown that APP-secretase activity is not inhibited by exogenously added proteinase inhibitors of different specificity (De Strooper, B., F. Van Leuven, and H. Van Den Berghe. 1992. FEBS (Fed. Eur. Biochem. Soc.) Lett. 308:50-53). We show here that the primary amine methylamine inhibits the secretion of APP into the medium. Furthermore, we show that a truncated form of APP, devoid of the cytoplasmic domain, is more efficiently cleaved and secreted than wild-type APP, which together with the methylamine block, shows that APP-secretase is located in a late compartment of the default constitutional secretion pathway. The sorting signals in the cytoplasmic domain of APP are therefore important in the deviation of APP from the secretase pathway. Finally we show that mutation of Arg609 to Asp in combination with Lys612 to Glu makes APP a less efficiently cleaved substrate for APP-secretase. The results are discussed in the context of recent findings on the targeting of APP and a parallel is drawn with some lysosomal glycoproteins that follow similar pathways. PMID- 8468349 TI - Retrieval of transmembrane proteins to the endoplasmic reticulum. AB - A COOH-terminal double lysine motif maintains type I transmembrane proteins in the ER. Proteins tagged with this motif, eg., CD8/E19 and CD4/E19, rapidly receive post-translational modifications characteristic of the intermediate compartment and partially colocalized to this organelle. These proteins also received modifications characteristic of the Golgi but much more slowly. Lectin staining localized these Golgi modified proteins to ER indicating that this motif is a retrieval signal. Differences in the subcellular distribution and rate of post-translational modification of CD8 maintained in the ER by sequences derived from a variety of ER resident proteins suggested that the efficiency of retrieval was dependent on the sequence context of the double lysine motif and that retrieval may be initiated from multiple positions along the exocytotic pathway. PMID- 8468350 TI - Apical polarization of N-CAM in retinal pigment epithelium is dependent on contact with the neural retina. AB - The retinal pigment epithelium (RPE) is unique among epithelia in that its apical surface does not face a lumen, but, instead, is specialized for interaction with the neural retina. The molecules involved in the interaction of the RPE with the neural retina are not known. We show here that the neural cell adhesion molecule (N-CAM) is found both on the apical surface of RPE in situ and on the outer segments of photoreceptors, fulfilling an important requisite for an adhesion role between both structures. Strikingly, culture of RPE results in rapid redistribution of N-CAM to the basolateral surface. This is not due to an isoform shift, since the N-CAM expressed by cultured cells (140 kD) is the same as that expressed by RPE in vivo. Rather, the reversed polarity of N-CAM appears to result from the disruption of the contact between the RPE and the photoreceptors of the neural retina. We suggest that N-CAM in RPE and photoreceptors participate in these interactions. PMID- 8468351 TI - Cross-linking of IgG receptors inhibits membrane immunoglobulin-stimulated calcium influx in B lymphocytes. AB - By cross-linking membrane immunoglobulins (mIg), the antigenic stimulation of B lymphocytes induces an increase in intracellular free calcium levels ([Ca2+]i) because of a combination of release from intracellular stores and transmembrane influx. It has been suggested that both events are linked, as in a number of other cases of receptor-induced increase in [Ca2+]i. Conversely, in B lymphocytes, type II receptors for the Fc fragment of IgG (Fc gamma RII) inhibit mIg-mediated signaling. Thus, we have investigated at the level of single cells if these receptors could act on specific phases of mIg Ca2+ signaling. Lipopolysaccharide-activated murine B splenocytes and B lymphoma cells transfected with intact or truncated Fc gamma RII-cDNA were used to determine the domains of Fc gamma RII implicated in the inhibition of the Ca2+ signal. [Ca2+]i was measured in single fura-2-loaded cells by microfluorometry. The phases of release from intracellular stores and of transmembrane influx were discriminated by using manganese, which quenches fura-2, in the external medium as a tracer for bivalent cation entry. The role of membrane potential was studied by recording [Ca2+]i in cells voltage-clamped using the perforated patch-clamp method. Cross linking of mIgM or mIgG with F(ab')2 fragments of anti-Ig antibodies induced a sustained rise in [Ca2+]i due to an extremely fast and transitory release of Ca2+ from intracellular stores and a long lasting transmembrane Ca2+ influx. The phase of influx, but not that of release, was inhibited by membrane depolarization. The increase in [Ca2+]i occurred after a delay inversely related to the dose of ligand. Co-cross-linking mIgs and Fc gamma RII with intact anti-Ig antibodies only triggered transitory release of Ca2+ from intracellular stores but no Ca2+ influx, even when the cell was voltage-clamped at negative membrane potentials. These transitory Ca2+ rises had similar amplitudes and delays to those induced by cross-linking mIgs alone. Thus, our data show that Fc gamma RII does not mediate an overall inhibition of mIg signaling but specifically affects transmembrane Ca2+ influx without affecting the release of Ca2+ from intracellular stores. Furthermore, this inhibition is not mediated by cell depolarization. Thus, Fc gamma RII represents a tool to dissociate physiologically the phases of release and transmembrane influx of Ca2+ triggered through antigen receptors. PMID- 8468352 TI - Dynamics of the neuronal intermediate filaments. AB - We have analyzed the dynamics of neuronal intermediate filaments in living neurons by using the method of photobleaching of fluorescently-labeled neurofilament L protein and immunoelectron microscopy of incorporation sites of biotinylated neurofilament L protein. Low-light-level imaging and photobleaching of growing axons of mouse sensory neurons did not affect the rate of either axonal growth or the addition of intermediate filament structures at the axon terminal, suggesting that any perturbations caused by these optical methods would be minimal. After laser photobleaching, recovery of fluorescence did occur slowly with a recovery half-time of 40 min. Furthermore, we observed a more rapid fluorescence recovery in growing axons than in quiescent ones, indicating a growth-dependent regulation of the turnover rate. Incorporation sites of biotin labeled neurofilament L protein were localized as numerous discrete sites along the axon, and they slowly elongated to become continuous arrays 24 h after injection. Collectively, these results indicate that neuronal intermediate filaments in growing axons turn over within the small area of the axoplasm possibly by the mechanism of lateral and segmental incorporation of new subunits. PMID- 8468353 TI - Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. AB - The existence of a neurofilament-deficient mutant of Japanese quail was recently documented (Yamasaki, H., C. Itakura, and M. Mizutani. 1991. Acta Neuropathol. 82:427-434), but the genetic events leading to the neurofilament deficiency have yet to be determined. Our molecular biological analyses revealed that the expression of neurofilament-L (NF-L) gene was specifically repressed in neurons of this mutant. To search for mutation(s) responsible for the shutdown of this gene expression, we cloned and sequenced the NF-L genes in the wild-type and mutant quails. It is eventually found that the NF-L gene in the mutant includes a nonsense mutation at the deduced amino acid residue 114, indicating that the mutant is incapable of producing even a trace amount of polymerization-competent NF-L protein at any situation. The identification of this nonsense mutation provides us with a solid basis on which molecular mechanisms underlying the alteration in the neuronal cytoskeletal architecture in the mutant should be interpreted. PMID- 8468354 TI - Carbohydrate recognition in the peripheral nervous system: a calcium-dependent membrane binding site for HNK-1 reactive glycolipids potentially involved in Schwann cell adhesion. AB - The carbohydrate determinants recognized by the HNK-1 antibody are potential cell cell recognition ligands in the peripheral nervous system (PNS). The HNK-1 reactive sulfoglucuronylneolacto (SGNL) glycolipids specifically support Schwann cell adhesion, suggesting the presence of a cell surface receptor specific for SGNL-oligosaccharides. We directly probed PNS membranes for receptors complementary to SGNL determinants using a synthetic radioligand consisting of radioiodinated serum albumin derivatized with multiple SGNL-oligosaccharides. A high-affinity, saturable, calcium-dependent binding site for this ligand was found in PNS myelin membranes. Binding activity was carbohydrate-specific (most potently inhibited by SGNL-lipids compared to other glycolipids) and PNS-specific (absent from comparable central nervous system membranes). The SGNL-specific binding activity on PNS membranes reported here may be involved in peripheral myelination or myelin stabilization. PMID- 8468356 TI - Inhibition of fibronectin binding and fibronectin-mediated cell adhesion to collagen by a peptide from the second type I repeat of thrombospondin. AB - The platelet and extracellular matrix glycoprotein thrombospondin interacts with various types of cells as both a positive and negative modulator of cell adhesion, motility, and proliferation. These effects may be mediated by binding of thrombospondin to cell surface receptors or indirectly by binding to other extracellular matrix components. The role of peptide sequences from the type I repeats of thrombospondin in its interaction with fibronectin were investigated. Fibronectin bound specifically to the peptide Gly-Gly-Trp-Ser-His-Trp from the second type I repeat of thrombospondin but not to the corresponding peptides from the first or third repeats or flanking sequences from the second repeat. The two Trp residues and the His residue were essential for binding, and the two Gly residues enhanced the affinity of binding. Binding of the peptide and intact thrombospondin to fibronectin were inhibited by the gelatin-binding domain of fibronectin. The peptide specifically inhibited binding of fibronectin to gelatin or type I collagen and inhibited fibronectin-mediated adhesion of breast carcinoma and melanoma cells to gelatin or type I collagen substrates but not direct adhesion of the cells to fibronectin, which was inhibited by the peptide Gly-Arg-Gly-Asp-Ser. Thus, the fibronectin-binding thrombospondin peptide Gly-Gly Trp-Ser-His-Trp is a selective inhibitor of fibronectin-mediated interactions of cells with collagen in the extracellular matrix. PMID- 8468355 TI - Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate. AB - Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of beta NGF or bFGF. It is equally effective in blocking neurite proliferation by 8-Br-cAMP. Zinc chloride and ammonium molybdate, two other inhibitors of tyrosine phosphatases, also cause parallel decreases in neurite proliferation. Orthovanadate generally reduces the transcription of immediate early response genes (TIS 8 and c-fos) and secondary response genes (ornithine decarboxylase (ODC), acetyl-cholinesterase (AChE) and SCG 10) induced by beta NGF, bFGF, EGF, and PMA, albeit in a variable fashion. There was no observed effect on the kinetics of expression as judged by TIS 8 induction by beta NGF and protein kinase C (PKC) downregulation did not change the levels of inhibition by orthovanadate seen in control cells. Orthovanadate does not affect the production of diacylglycerol induced by beta NGF or bFGF. These observations are consistent with the view that growth factor stimulation of differentiation in PC12 cells involves at least one other PKC independent pathway, and that cAMP and PMA (and their active analogs) activate tyrosine kinases (albeit probably secondarily), which are at least partially responsible for their actions. Although the exact site(s) of action of orthovanadate that lead to the inhibition of growth factor-induced neurite proliferation are unknown, the results presented suggest that it prolongs tyrosine phosphorylations by nonreceptor tyrosine kinases that act downstream from the receptor kinases. PMID- 8468357 TI - Long-term culture of disaggregated rat osteoclasts: inhibition of bone resorption and reduction of osteoclast-like cell number by calcitonin and PTHrP[107-139]. AB - The isolated osteoclast bone resorption assay has proved to be a useful means of examining the response of mammalian and avian osteoclasts to a variety of stimuli. The assay has traditionally been performed over a period of 24 hours. By extending the duration of the osteoclast bone resorption assay, we have been able to assess the long-term effects of carboxyl-terminal parathyroid hormone-related protein (hPTHrP[107-139]), salmon calcitonin (sCT) and hPTH[1-34] on bone resorption and TRACP-positive osteoclast-like cell number. We found that, in control cultures over a period of up to 144 hours, the osteoclast-like cells not only remained viable but their numbers also increased. The number of mononucleated and multinucleated osteoclast-like cells doubled in the first 48 hours before stabilizing over the remainder of the incubation period. Osteoblasts also proliferated, resulting in a resorption response to hPTH[1-34] being evident from 48 hours onward. hPTHrP]107-139] persistently inhibited basal and PTH stimulated bone resorption for at least 96-144 hours, whereas "escape" from the inhibitory effect of sCT was seen after 48-72 hours. Decreased numbers of both mononucleated and multinucleated TRACP-positive osteoclast-like cells were seen by 48 hours in cultures treated with sCT. In contrast, hPTHrP[107-139] reduced the number of mononuclear TRACP-positive cells with only a late effect on multinucleated cells. Furthermore, the increased number of osteoclast-like cells seen in response to hPTH[1-34] was inhibited by carboxyl-terminal PTHrP. In summary, this study indicates that the extended bone resorption assay system is a complex one where both osteoclastic resorption and osteoclast maturation are evident. Using this system, we have shown that hPTHrP[107-139] acts as a potent long-term inhibitor of osteoclastic bone resorption, without evidence of escape from its effect. Its action to reduce the number of mononucleated osteoclast-like cells suggests that it affects several aspects of osteoclast activity. PMID- 8468358 TI - Dissociation of early and late markers of murine myeloid differentiation by interferon-gamma and interleukin-6. AB - Murine myeloid leukemia M1 cells undergo terminal differentiation to mature macrophages after stimulation with interleukin-6 (IL-6). This process can be monitored by measuring the expression of early markers such as the high affinity receptor for monomeric IgG2a (Fc gamma RI) and Ia antigen followed by late markers such as lysozyme production and finally morphological changes from blast cells to mature macrophages. The same early markers that are expressed on M1 cells after induction with IL-6 are also expressed on monocytic cells after activation with interferon-gamma (IFN gamma). We used IL-6 and IFN gamma to investigate whether the early stages of M1 cell differentiation could be accomplished without commitment of the cells to terminal differentiation. Cytofluorometry shows that the expression of the same early differentiation markers (Fc gamma RI and Ia antigen) that are inducible by IL-6 on M1 cells can be induced by IFN gamma as well. However, stimulation with IFN gamma, in contrast to IL-6, does not induce the late differentiation markers such as lysozyme production, phagocytic activity, and morphological changes. Northern analysis supports these findings in that expression of Fc gamma RI mRNA is induced by either cytokine, whereas expression of mRNA for lysozyme is inducible by IL-6 only. Nuclear run-on analysis reveals that the changes in steady state mRNA levels of both Fc gamma RI and lysozyme are regulated by a transcriptional mechanism. These data suggest that early stages in the process of myeloid differentiation can be separately induced by IFN gamma and thus are independent from the later events induced by IL-6. PMID- 8468359 TI - Adhesiveness and proliferation of epithelial cells are differentially modulated by activation and inhibition of protein kinase C in a substratum-dependent manner. AB - In the present study, we have examined the regulation of attachment, onset of proliferation and the subsequent growth, in vitro, of chick retinal pigmented epithelial (RPE) cells as a function of the nature of the substratum and of either the activation or inhibition of protein kinase C (PKC). The RPE cells have an adhesive preference for protein carpets which contain laminin. This preference disappears gradually with time in culture. The adhesion of RPE cells to fibronectin is shown to be a receptor-mediated process which involves the RGD recognition signal. This study also demonstrates that a PKC activator, 12-O tetradecanoyl-phorbol-13-acetate (TPA), affects RPE cell adhesion in a substratum dependent manner. Exposure of RPE cells to TPA lowers the cell attachment efficacy to ECM protein substrata but does not affect cell attachment to plastic. The onset of cell proliferation is accelerated by TPA on all of the substrata tested. The minimal duration of an effective TPA pulse exerting a long-lasting influence on RPE cell proliferation is between 1.5 and 3.5 hr. Stimulation of cell proliferation by TPA in long-term cultures is independent of the nature of the growth substratum. The acceleration of the onset of cell proliferation by TPA is sensitive to 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), an inhibitor of conventional PKC, and thus appears to be dependent on the activation of conventional PKC. H7 also affects cell-cell contacts, causing an alteration in the shape ("squaring") of RPE cells packed into large colonies. Conversely, the effects of TPA on both the attachment and the long-term proliferation of RPE cells are not dependent a conventional PKC isotype, since H7 cannot abolish the influence of TPA on either process. We conclude that the effect of TPA on long term proliferation of RPE cells is either dependent on a novel PKC isotype or independent of PKC. PMID- 8468360 TI - Modulation of transforming growth factor-beta 1 stimulated elastin and collagen production and proliferation in porcine vascular smooth muscle cells and skin fibroblasts by basic fibroblast growth factor, transforming growth factor-alpha, and insulin-like growth factor-I. AB - During tissue repair and development, matrix accumulation is modulated as multiple signals impinge on target cells. We have investigated the effects of combinations of the mitogenic cytokines, basic fibroblast growth factor (bFGF), transforming growth factor alpha (TGF-alpha), and insulin-like growth factor-1 (IGF-1) with transforming growth factor-beta 1 (TGF-beta 1) with respect to the production of two matrix components, elastin and type I collagen. Using specific enzyme-linked immunoassays for detection of secreted precursors in both vascular smooth muscle cells and skin fibroblasts from the domestic pig, production of these two fibrous proteins was shown to be strongly stimulated by TGF-beta 1. In the smooth muscle cell, both bFGF and TGF-alpha were potent antagonists of TGF beta 1-mediated matrix production, whereas IGF-1 was only weakly additive with respect to elastin production. Antagonism was also evident to a lesser extent in skin fibroblasts. Reduced responsiveness to TGF-beta 1 did not appear to be due to a switch to a proliferative state, since TGF-beta 1 itself acted as a mitogen in confluent SMC, and TGF-alpha was only a weak mitogen in confluent fibroblast cultures. Although a predominant effect of TGF-beta is matrix accumulation, these findings suggest that this property will be significantly modified by the cytokine context. PMID- 8468361 TI - Expression and function of gingival fibroblast C1q receptors are upregulated by interleukin-1 beta and transforming growth factor-beta. AB - In injury and inflammation, complement (C) component C1q, in addition to its central role in initiation of classical pathway of complement activation, modulates diverse cellular functions by binding to specific cell surface receptors. Interaction of substrate-bound C1q with receptors for the collagen like domain of C1q (C1qRC) of human gingival fibroblasts (HGF) promotes cell attachment. We investigated modulation of the adhesive function and expression of C1qRC by interleukin-1 beta (IL-1 beta) and transforming growth factor-beta (TGF beta). Confluent fibroblast monolayers were incubated under standard culture conditions with or without cytokines. C1qRC function was measured by attachment assays. IL-1 beta and TGF-beta increased fibroblast adhesion to C1q to 146% and 131% of controls, respectively. Cytokine enhancement of HGF adhesion was concentration-dependent, saturable (20 ng/ml IL-1 beta; 1 ng/ml TGF-beta) and time-dependent (IL-1 beta 12-hr peak; TGF-beta 24-hr peak). Effect of IL-1 beta and TGF-beta on C1qRC expression was assessed by flow cytometry measurements of fluorescence intensity of cells stained with C1q and FITC anti-C1q antibody, and by binding studies with 125I-C1q. Cells treated with cytokines displayed a two- to four-fold increased fluorescence of cell-bound C1q compared to controls. Binding studies indicated the increased fluorescence correlated with increase in number of C1qRC in both IL-1 beta (4.7 x 10(6)/cell) and TGF-beta (3.9 x 10(6)/cell)-treated cells, compared to control (3.0 x 10(6)/cell), but had no effect on binding affinity. Rates of internalization of receptor-bound C1q were similar in cytokine-treated cells and controls. We propose from these data that IL-1 beta and TGF-beta have the ability to upregulate C1qRC expression, and this effect contributes to increased adhesion of HGF to substrate-bound C1q. PMID- 8468362 TI - Epidermal growth factor receptors lose ligand binding ability as WI-38 cells progress from short-term to long-term quiescence. AB - WI-38 cells, density arrested for short periods of time, can be stimulated to re enter the cell cycle by epidermal growth factor (EGF) alone. However, cells density arrested for longer periods have a prolonged prereplicative phase when serum stimulated and cannot be stimulated by EGF alone. Radio-ligand binding studies performed on WI-38 cells showed that actively growing cells bind [125I]EG at relatively low levels that increase to a maximum as the cells become contact inhibited. As the cells enter a state of deeper quiescence, EGF binding falls to one-third to one-fifth the short-term growth arrested levels, remaining constant thereafter. The EGF-receptor complexes internalize more slowly in long-term growth arrested cells, and the rate of ligand association to the receptor is lower than short-term growth arrested cells. The amount of EGF receptor protein in lysates of equal numbers of both short- and long-term quiescent cells remains the same. These results suggest that the failure of long-term growth arrested cells to respond to EGF is not due to dramatic changes in the amount of receptor protein during prolonged quiescence but more likely to an alteration in the ability of these receptors to bind ligand and/or activate the EGF signal transduction pathway. PMID- 8468363 TI - Effects of growth factors on cell cycle arrest in dolichyl phosphate-depleted cultures. AB - Previously we showed that CHO cell growth is arrested in the G1 or G0 phase within 24 h after the biosynthesis of mevalonic acid is blocked. The growth limiting factor under these conditions appeared to be dolichyl phosphate or one of its glycosylated derivatives with consequent decrease in the synthesis of N linked glycoproteins (Doyle, J.W., and A.A. Kandutsch, 1988, J. Cell Physiol. 137:133-140; Kabakoff, B., J.W. Doyle, and A.A. Kandutsch, 1990, Arch. Biochem. Biophys. 276:382-389). We show herein that cell surface glycoproteins are depleted in the inhibited cultures and that growth arrest is delayed when supraphysiological concentrations of insulin, insulin-like growth factor-1 (IGF 1) and bFGF are added to the culture medium. Apparently an elevated level of a growth factor increases the length of time during which a threshold level of occupied receptor is maintained as the number of glycosylated receptor molecules declines. The results support the idea that cellular levels of dolichyl phosphate and its derivatives may limit cell division by controlling the numbers of functional receptors for growth factors and of other glycoproteins on the cell surface. PMID- 8468364 TI - Mutant cell line demonstrating a block in insulin and insulin-like growth factor type 1 (IGF-1) induced mitogenesis. AB - Recently, we have isolated a Chinese hamster cell variant (IV-A1-j) resistant to an insulin-diphtheria-A chain toxic conjugate (Leckett and Germinario: Cytotechnology [in press]. This cell line exhibited a decreased level of insulin binding, but normal growth in serum-containing medium when compared to the parental cell line (V-79). In this paper we further demonstrate that while IV-A1 j cells are capable of growing in serum-containing medium, they are insensitive to the mitogenic actions of either insulin or IGF-1. In contrast, epidermal growth factor (EGF) and/or alpha-thrombin (THR) generate a mitogenic effect in IV A1-j cells comparable to that observed in the parental V-79 cells. The combination of EGF and/or THR with either insulin or IGF-1 results in an increase in V-79 cell growth above EGF and/or THR alone. On the other hand, insulin or IGF 1 in the presence of other mitogens did not stimulate further growth in IV-A1-j cells. While insulin binding was lower in IV-A1-j cells, internalization of 125I insulin was not different in the two cell types. Additionally, insulin-stimulated glycogen synthesis and protein synthesis were not different in the two cell types. These observations are consistent with insulin and IGF-1 sharing a mitogenic signalling pathway in Chinese hamster fibroblasts and that this pathway is distinct from other growth factor signalling pathways. The fact that this pathway is defective in the IV-A1-j cell line indicates the potential usefulness of these cells in identifying a key step(s) in the insulin (IGF-1) mitogenic pathway. PMID- 8468365 TI - Heparin-like glycosaminoglycans participate in binding of a human trophoblastic cell line (JAR) to a human uterine epithelial cell line (RL95). AB - In vitro studies in our laboratory have indicated that heparan sulfate proteoglycans (HSPGs) play an important role in murine embryo implantation. In order to investigate the potential function of HSPGs in human implantation, two human cell lines (RL95 and JAR) were used to model uterine epithelium and embryonal trophectoderm, respectively. A heterologous cell-cell adhesion assay was developed to determine if binding of JAR cells to RL95 cells was heparan sulfate-dependent. Labeled, single cell suspensions of JAR cells attached to confluent monolayers of RL95 cells in a dose- and time-dependent manner. Heparin like glycosaminoglycans and JAR cell proteoglycans competitively inhibited JAR cell adhesion to RL95 cells by 50% or more. A panel of chemically modified heparins were used to demonstrate that O-sulfation and amino group substitution were critical for inhibition of cell-cell adhesion. Treatment with chlorate, an inhibitor of ATP-sulfurylase, resulted in a 56% reduction in cell-cell binding compared to untreated controls. Heparinase and chondroitinase ABC markedly inhibited JAR-RL95 binding, while chondroitinase AC had no significant effect. These observations indicated that HSPGs as well as dermatan sulfate-containing proteoglycans participated in cell-cell binding. Collectively, these results indicate that initial binding interactions between JAR and RL95 cells is mediated by cell surface glycosaminoglycans (GAGs) with heparin-like properties (i.e., heparan sulfate and dermatan sulfate). These observations are consistent with an important role for HS and heparin-like GAGs as well as their corresponding binding sites in early stages of human trophoblast-uterine epithelial cell binding. PMID- 8468366 TI - Regulation of malic enzyme gene expression by nutrients, hormones, and growth factors in fetal hepatocyte primary cultures. AB - The culture of fetal hepatocytes for 64 h in medium supplemented with 5 mM glucose, T3, insulin, and dexamethasone resulted in the coordinate precocious expression of malic enzyme mRNA, protein, and specific activity. T3 was the main inducer; meanwhile, insulin exerted a small synergistic effect when added with T3. Dexamethasone had a potentiation effect on the T3 response of malic enzyme mRNA expression regardless of the presence of insulin. This effect of dexamethasone on T3 response of malic enzyme mRNA expression was time (64 h) and glucose dependent. Glucagon, and to a greater degree dibutyryl-cAMP, repressed malic enzyme mRNA as well as protein expression by T3 and dexamethasone, in the absence of insulin. Glucose and other carbon sources such as lactate-pyruvate or dihydroxyacetone induced the abundance of malic enzyme mRNA in the absence of hormones. Insulin and T3 produced a high accumulation of malic enzyme mRNA in lactate-pyruvate medium, this effect being decreased by dexamethasone. EGF suppressed the induction produced by T3 and dexamethasone on malic enzyme mRNA, while the expression of beta-actin mRNA remained essentially unmodified. PMID- 8468367 TI - Synergistic effects of cytokine and hyperthermia on cytotoxicity in HT-29 cells are not mediated by alteration of induced protein levels. AB - In this study, we investigated the mechanism of synergistic effects of cytokine and hyperthermia on cytotoxicity in HT-29. When cells were heated at 42 degrees C in the presence of recombinant human tumor necrosis factor (rhTNF-alpha), recombinant interferon-gamma (rhIFN-gamma), or in a combination of both, a synergistic increase in the cytotoxic effects of the respective drugs was observed. We hypothesized that alteration of cytokine or heat-induced polypeptides synthesis was responsible for a synergistic interaction between heat and cytokine. Five heat shock proteins (HSPs, M(r) 110,000, 100,000, 90,000, 70,000, and 28,000) were preferentially synthesized during chronic heating at 42 degrees C. In contrast, the synthesis of two proteins (M(r) 60,000 and 29,000) was induced by treatment with rhIFN-gamma (1,000 U/ml). Although the combination of chronic hyperthermia (42 degrees C) with TNF-alpha, IFN-gamma, or TNF-alpha + IFN-gamma increased cytotoxicity, alteration/induction of polypeptides was not correlated with the synergistical cytotoxic effects of cytokine and heat. Thus, the synergistic effects of cytokine and hyperthermia are not mediated through an induction of polypeptides. PMID- 8468368 TI - Role of Ca2+ in stimulation of DNA synthesis by epidermal growth factor and tumor promoters in cultured rat hepatocytes. AB - This study examines the effects of extracellular Ca2+ concentrations, [Ca2+]o, and of treatments known to modulate intracellular Ca2+ levels on the extent and timing of DNA synthesis in primary cultures of adult rat hepatocytes. In cultures exposed to insulin and EGF, the extent of DNA synthesis between 40 h and 70 h in culture was independent of [Ca2+]o in the range 25-1,800 microM, although the peak of DNA synthesis occurred 5-10 h earlier with 1.2 mM Ca2+ than with 25 microM Ca2+. Complete removal of extracellular Ca2+ using EGTA blocked DNA synthesis if Ca2+ was removed on the second day after EGF addition but not if Ca2+ was absent only on day 1. Treatment of cultures in 1.2 mM Ca(2+)-containing media with Ca(2+)-ionophore A23187 or with thapsigargin, agents expected to raise cytosolic [Ca2+], failed to augment the stimulation of DNA synthesis by EGF. These observations suggest that hepatocytes may have a permissive requirement for [Ca2+]o > 0 at least late in the sequence of events leading from growth factor stimulation to DNA synthesis. However, sustained elevation of cytosolic [Ca2+] does not appear to be important as an early signalling event either in mediating or augmenting EGF action in hepatocytes. The ability of liver tumor promoters alpha-hexachlorocyclohexane or DDT to stimulate DNA synthesis in combination with EGF was independent of [Ca2+]o. By contrast, the skin tumor-promoting phorbol ester, TPA, or liver tumor promoter, phenobarbital, were without effect or inhibitory at low [Ca2+]o but in combination with EGF, stimulated DNA synthesis at [Ca2+]o > 0.4 mM, suggesting that Ca2+ may have some role in mediating or modulating the stimulatory effects of these agents. PMID- 8468369 TI - Regulation of chicken Hsp70 and Hsp90 family gene expression by transforming growth factor-beta 1. AB - Transforming growth factor-beta 1 (TGF beta) is a regulator of protein synthesis in cultured chicken embryo cells (CEC). Preceding a gradual increase in overall protein synthesis, members of the Hsp70 family (Hsp70, Hsc70, and Grp78) and the Hsp90 family (90-2 and 90-3) of molecular chaperones are induced rapidly and represent a new class of TGF beta-inducible proteins (I.M. Takenaka and L.E. Hightower, J. Cell. Physiol., 152:568-577, 1992). Herein, 32P-labeled cDNA probes encoding Hsc70 and Hsp90 were used to show that levels of the corresponding mRNAs increased as a fraction of total RNA and in polysomes within five hours of treatment of CEC with TGF beta. This cytokine did not increase rates of hsc70 and hsp90 gene transcription as measured by run-on transcription assays of isolated nuclei. However, the Hsp RNA inductions were inhibited by dactinomycin, indicating a requirement for newly synthesized RNA. Both Hsc70 and Hsp90 mRNAs had relatively short half-lives, measured by Northern blot analyses of dactinomycin chases, which were not altered substantially in TGF beta-treated cells. In contrast, Hsp mRNA half-lives increased in heat shocked CEC exposed to dactinomycin during recovery, revealing a difference in regulation of these genes in stressed cells compared with TGF beta-treated cells. Our results support the conclusion that hsc70 and hsp90 gene expression is regulated posttranscriptionally in TGF beta-treated CEC, and the mechanism likely involves a nuclear event such as increasing the half-lives of nuclear RNA transcripts, processing, or transport into the cytoplasm. PMID- 8468370 TI - Mechanical stimulation of skeletal muscle generates lipid-related second messengers by phospholipase activation. AB - Repetitive mechanical stimulation of cultured avian skeletal muscle increases the synthesis of prostaglandins (PG) E2 and F2 alpha which regulate protein turnover rates and muscle cell growth. These stretch-induced PG increases are reduced in low extracellular calcium medium and by specific phospholipase inhibitors. Mechanical stimulation increases the breakdown rate of 3H-arachidonic acid labelled phospholipids, releasing free 3H-arachidonic acid, the rate-limiting precursor of PG synthesis. Mechanical stimulation also increases 3H-arachidonic acid labelled diacylglycerol formation and intracellular levels of inositol phosphates from myo-[2-3H]inositol labelled phospholipids. Phospholipase A2 (PLA2), phosphatidylinositol-specific phospholipase C (PLC), and phospholipase D (PLD) are all activated by stretch. The stretch-induced increases in PG production, 3H-arachidonic acid labelled phospholipid breakdown, and 3H arachidonic acid labelled diacylglycerol formation occur independently of cellular electrical activity (tetrodotoxin insensitive) whereas the formation of inositol phosphates from myo-[2-3H]inositol labelled phospholipids is dependent on cellular electrical activity. These results indicate that mechanical stimulation increases the lipid-related second messengers arachidonic acid, diacylglycerol, and PG through activation of specific phospholipases such as PLA2 and PLD, but not by activation of phosphatidylinositol-specific PLC. PMID- 8468371 TI - Effects of epidermal growth factor, estrogen, and progestin on DNA synthesis in mammary cells in vivo are determined by the developmental state of the gland. AB - Estrogen (E), progesterone (P), and epidermal growth factor (EGF) are involved in the growth and development of the normal mammary gland. While studies have been carried out to investigate the in vivo effects of EGF in the immature mammary gland, nothing is known about the growth effects of EGF or its potential interactions with E and/or P in the adult mammary gland. The present studies were undertaken to investigate the effects of EGF, E, and P on mammary cell proliferation in immature, peripubertal vs. adult, sexually mature mice. We have found that EGF promotes epithelial and stromal cell proliferation in both the immature and adult mammary glands. In the immature gland, the end bud epithelium is most responsive to the proliferative effects of EGF and there is no apparent interaction between EGF, E, and/or P. In contrast, in the mature gland EGF adds to the proliferative effects of E+P in the ductal epithelium resulting in more extensive ductal sidebranching. Thus these results demonstrate that the developmental state of the mammary gland determines the nature and extent of the interactions between EGF, E, and P in growth and development. PMID- 8468372 TI - Cell density, negative proliferation control, and phosphorylation of retinoblastoma protein. AB - Cell density negative control (CDNC) of normal human fibroblast proliferation occurs after stimulation by mitogens with different signal transduction mechanism. Delayed exposure to agents that interfere with CDNC, such as double stranded RNA and vanadate, reveals the existence of a biochemical event, involved in CDNC, that occurs 5-8 hr after the beginning of mitogenic stimulation. This is earlier than the point of "mitogenic commitment," defined by the duration of mitogen exposure required for cell cycle entry (8-18 hr). Phosphorylation of the retinoblastoma gene product (pRB) begins 8-10 hr after mitogen stimulation and is nearly complete at 18 hr, just as the first cells enter S-phase. CDNC prevents pRB phosphorylation. Interferon beta delays pRB phosphorylation by up to 20 hr but has little effect on the timing of mitogenic commitment. Thus mitogenic commitment is located in time between CDNC and pRB phosphorylation. When agents that cause a release from CDNC are applied to dense, negatively controlled cultures after 18 hr of EGF stimulation, pRB phosphorylation occurs 6-8 hr after release. This suggests that the negatively controlled cells process the mitogenic signal but accumulate at a restriction point. The relatively early timing of CDNC related events in the prereplicative phase raises the possibility that pRB phosphorylation is a consequence rather than a prerequisite for release from cell density negative control. PMID- 8468373 TI - Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in renal epithelial LLC-PK1 cells. AB - We have studied arginine vasopressin (AVP)-, thapsigargin- and inositol 1,4,5 trisphosphate (InsP3)-mediated Ca2+ release in renal epithelial LLC-PK1 cells. AVP-induced changes in the intracellular free calcium concentration ([Ca2+]i) were studied in indo-1 loaded single cells by confocal laser cytometry. AVP mediated Ca2+ mobilization was also observed in the absence of extracellular Ca2+, but was completely abolished after depletion of the intracellular Ca2+ stores by 2 microM thapsigargin. Using 45Ca2+ fluxes in saponin-permeabilized cell monolayers, we have analysed how InsP3 affected the Ca2+ content of non mitochondrial Ca2+ pools in different loading and release conditions. Less than 10% of the Ca2+ was taken up in a thapsigargin-insensitive pool when loading was performed in a medium containing 0.1 microM Ca2+. The thapsigargin-insensitive compartment amounted to 35% in the presence of 110 microM Ca2+, but Ca2+ sequestered in this pool could not be released by InsP3. The thapsigargin sensitive Ca2+ pool, in contrast, was nearly completely InsP3 sensitive. A submaximal [InsP3], however, released only a fraction of the sequestered Ca2+. This fraction was dependent on the cytosolic as well as on the luminal [Ca2+]. The cytosolic free [Ca2+] affected the InsP3-induced Ca2+ release in a biphasic way. Maximal sensitivity toward InsP3 was found at a free cytosolic [Ca2+] between 0.1 and 0.5 microM, whereas higher cytosolic [Ca2+] decreased the InsP3 sensitivity. Other divalent cations or La3+ did not provoke similar inhibitory effects on InsP3-induced Ca2+ release. The luminal free [Ca2+] was manipulated by varying the time of incubation of Ca(2+)-loaded cells in an EGTA-containing medium. Reduction of the Ca2+ content to one-third of its initial value resulted in a fivefold decrease in the InsP3 sensitivity of the Ca2+ release. PMID- 8468374 TI - Improved assay for the quantification of 11-dehydrothromboxane B2 by gas chromatography-mass spectrometry. AB - Endogenous thromboxane production is best assessed by the measurement of its excreted metabolites, of which 11-dehydrothromboxane B2 (11-dehydro-TxB2) is most abundant. Gas chromatographic-mass spectrometric assays have been developed for this compound but suffer from the presence of co-eluting impurities which make the measurement of 11-dehydro-TxB2 difficult. Furthermore, these assays are often time-consuming. We now report a modified assay for the measurement of this compound employing gas chromatography-mass spectrometry which alleviates the problem of co-eluting impurities primarily through modification of extraction and chromatographic methods. Furthermore, the time to complete the assay is significantly shortened. It is adaptable to both urine and plasma. Precision of the assay is +/- 7% and accuracy is 90%. The lower limit of sensitivity in urine is approximately 20 pg/mg creatinine. Normal levels of urinary excretion of this metabolite were found to be 370 +/- 137 pg/mg creatinine (mean +/- 1 S.D.) and normal plasma levels were found to be 1.5 +/- 0.4 pg/ml (mean +/- 1 S.D.). Urinary excretion of 11-dehydro-TxB2 is markedly altered in situations associated with abnormalities in thromboxane generation when quantified using this assay. Thus, this assay provides a sensitive and accurate method to assess endogenous thromboxane production and to further explore the role of this compound in human disease. PMID- 8468375 TI - Determination of tryptophan in human serum by high-performance liquid chromatography with pre-column fluorescence derivatization using phenylglyoxal. AB - A high-performance liquid chromatographic method based on pre-column fluorescence derivatization with phenylglyoxal is described for the sensitive and selective quantification of total (free plus albumin-bound) and free tryptophan in serum. Serum was deproteinized with perchloric acid for total tryptophan and by ultrafiltration for free tryptophan, and then subjected to fluorescence derivatization. The reaction mixture was separated on a reversed-phase column by isocratic elution and the tryptophan derivative was then detected by fluorimetry. The method was at least ten-fold more sensitive than other conventional chromatographic methods with no derivatization. The lower limit of determination (signal-to-noise ratio = 3) for endogenous tryptophan in human serum was 72 nmol/l, which corresponds to 200 fmol on-column. PMID- 8468376 TI - Use of guanidine hydrochloride and ammonium sulfate in comprehensive in-line sorption enrichment of xenobiotics in biological fluids by high-performance liquid chromatography. AB - A novel approach has been developed for direct injection of physiological fluids on an in-line extraction pre-column followed by column switching in order to introduce the adsorbed xenobiotic onto the analytical column. The physiological fluid is pre-treated with guanidinium solution in water (200 microliters of fluid plus 300 microliters of a reagent containing 8.05 M guanidinium and 1.02 M ammonium sulfate) in order to denature protein binding sites and to serve as a universal solvent for a divergent range of polar to non-polar xenobiotics in a hydrophilic medium. A 0.5 M ammonium sulfate solution (500 microliters) is used as a pre- and post-flush reagent for the extraction pre-column (30 mm x 2.1 mm I.D.). The pre-flush reagent prepares the sorbent environment of the C18 pre column for the hydrophobic retention of analytes. The post-flush reagent flushes non-retained sample proteins and salts to waste prior to switching the pre-column in-line with the analytical column. Universal chromatographic conditions for the analytical phase allows elution of a range of polar to non-polar xenobiotics within 20 min from an end-capped C8 silica analytical column (250 mm x 4.6 mm I.D.). This is effected by a linear gradient from a binary system consisting of solvent A (0.05 M KH2PO4) and solvent B (acetonitrile-isopropanol, 80:20, v/v). PMID- 8468377 TI - Analyses of volatile C2 haloethanes and haloethenes in tissues: sample preparation and extraction. AB - A tissue extraction procedure was developed which minimized loss of readily volatilizable compounds for subsequent quantification by headspace gas chromatography, and evaluated for perchloroethylene (PER), 1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, and 1,1,2-trichloroethylene. Of the procedures evaluated, joint isooctane and saline tissue homogenization had the most efficient recovery, ranging from 73 to 104% for the four halocarbons from seven different rat tissues. PER concentrations were also determined in tissues of rats following in vivo halocarbon administration. Recovery did not appear to be tissue dependent, but did vary somewhat with test chemical, with the least volatile, most lipophilic compounds exhibiting the highest recovery. PMID- 8468378 TI - Determination of nicotine and two major metabolites in serum by solid-phase extraction and high-performance liquid chromatography, and high-performance liquid chromatography-particle beam mass spectrometry. AB - A rapid and selective assay of nicotine, cotinine and trans-3'-hydroxycotinine in human serum, based on high-performance liquid chromatography with UV detection has been developed. The compounds were subjected to solid-phase extraction, using Extrelut 1 cartridges. Recoveries were ca. 95% for nicotine, 90% for cotinine and 50-55% for trans-3'-hydroxycotinine. The limit of quantitation observed with this method was 10 ng/ml for nicotine and 5 ng/ml for each of the metabolites. The compounds were also identified using high-performance liquid chromatography with particle beam mass spectrometry, to confirm their presence in human serum. PMID- 8468379 TI - Direct high-performance liquid chromatographic determination in urine of the enantiomers of propranolol and its major basic metabolite 4-hydroxypropranolol. AB - A method is described for quantitation of underivatized enantiomers of propranolol and its major basic metabolite, 4-hydroxypropranolol, in urine samples by high-performance liquid chromatography with fluorescence detection, using a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase. This method was found to be precise and accurate for the measurement of propranolol and 4-hydroxypropranolol concentrations in urine from pharmacokinetic investigations. This method represents the first assay for direct determination of 4-hydroxypropranolol enantiomers. The ability to easily measure 4 hydroxypropranolol enantiomers is valuable because the stereoselective disposition of propranolol is primarily due to stereoselective metabolism in the pathway responsible for generation of 4-hydroxypropranolol. PMID- 8468380 TI - Achiral and chiral high-performance liquid chromatographic determination of tramadol and its major metabolites in urine after oral administration of racemic tramadol. AB - A reversed-phase high-performance liquid chromatographic method for the simultaneous determination of tramadol and its major metabolites O demethyltramadol and N-demethyltramadol in urine has been developed. The determination of the enantiomeric ratios of the three compounds was achieved using a Chiralpak AD column and a Chiralcel OD column, respectively. After oral administration of racemic tramadol to five healthy volunteers, inter-individual differences of the excreted amounts and the enantiomeric ratios of the compounds were observed. PMID- 8468381 TI - Stereoselective high-performance liquid chromatographic assay for the determination of sotalol enantiomers in biological fluids. AB - A high-performance liquid chromatographic (HPLC) assay for determination of sotalol enantiomers in biological fluids was developed to assess the stereoselective disposition of the drug in man. Following extraction at pH 9.0 with a mixture of chloroform-isopropanol (3:1, v/v), the organic phase was evaporated to dryness and the residue derivatized with (-)-methyl chloroformate. Diastereoisomeric derivatives were resolved by HPLC (C8 column) with fluorescence detection (lambda ex = 235 nm and lambda em = 300 nm). Retention times of l- and d-sotalol derivatives were 13 and 15 min while that of the internal standard, S-( )-atenolol, was 12.3 min. The detection limit of each enantiomer was 12.5 ng/ml using 1 ml of plasma or urine. Intra-day and inter-day coefficients of variation were less than 10% for each enantiomer in the range 0.125-2.5 micrograms/ml in plasma and 0.25-2.5 micrograms/ml in urine. PMID- 8468382 TI - Improved detection limits for screening of diuretics by coupled liquid chromatography and ultraviolet-visible spectrophotometry. AB - Experimental conditions have been studied in order to improve the sensitivity for the analysis of diuretics and probenecid in urine samples by high-performance liquid chromatography with ultraviolet detection. Sample clean-up and chromatographic parameters have been optimized to obtain a suitable sensitivity for the detection or quantification of each diuretic using an HP-Hypersil ODS-C18 column (5 microns, 250 mm x 4 mm I.D.), taking into account the pharmacological properties of each compound. The reliability of this method was tested by analysing urine samples after a minimum single-dose administration of chlorthalidone and probenecid. PMID- 8468383 TI - Determination of dapoxetine, an investigational agent with the potential for treating depression, and its mono- and di-desmethyl metabolites in human plasma using column-switching high-performance liquid chromatography. AB - A column-switching high-performance liquid chromatographic (HPLC) method is described for the determination of dapoxetine and its mono- and di-desmethyl metabolites in human plasma. The analytes, including an internal standard, were extracted from plasma at basic pH with hexane-ethyl acetate. The organic extract was evaporated to dryness and the residue reconstituted with acetonitrile. The analytes were separated from late-eluting endogenous substances on a Zorbax RX-C8 pre-column. The front-cut fraction containing the analytes was further separated on a second RX-C8 column. The analytes were detected by their native fluorescence, using excitation and emission wavelengths of 230 and 330 nm, respectively. The limit of quantitation was determined to be 20 ng/ml, and the response was linear from 20 to 200 ng/ml. The method has been successfully applied to human plasma samples in a Phase I study. PMID- 8468384 TI - Sensitive high-performance liquid chromatographic determination of 2,2'-[(2 aminoethyl)imino]diethanol bis(butylcarbamate) and its metabolites in human serum following pre-column derivatization with o-phthalaldehyde and stabilization of the derivatives. AB - A high-performance liquid chromatographic method for the sensitive determination of 2,2'-[(2-aminoethyl)imino]diethanol bis(butylcarbamate) (I) and its metabolites in human serum has been developed. The method was based on a pre column derivatization with o-phthalaldehyde. The derivatives were stabilized at least for 24 h at 4 degrees C by using N-acetyl-L-cysteine as a thiol and by eliminating the excess o-phthalaldehyde in the reaction mixture by solvent extraction and the addition of an ammonium salt after the reaction. The recoveries and reproducibilities in human serum spiked with I and its two metabolites were satisfactory, and the responses were linear over a wide range of analyte concentrations. The detection limits of I and its metabolites, II and III, in serum were 0.5, 4 and 2 ng/ml, respectively, at a signal-to-noise ratio of 5. The method was satisfactorily applied to the clinical study of I. PMID- 8468385 TI - Simultaneous high-performance liquid chromatographic assay of droperidol and flunitrazepam in human plasma. Application to haemodilution blood samples collected during clinical anaesthesia. AB - A simultaneous assay for droperidol and flunitrazepam by high-performance liquid chromatography has been developed and applied to blood samples collected during an acute normovolemic haemodilution under general anaesthesia. Haemodilution blood samples were stored at +4 degrees C to be transfused, if required, to a patient during the post-surgical phase. A C18 Supelclean cartridge was used for solid-phase extraction, and the recoveries were 74% and 89%, respectively, for droperidol and flunitrazepam. Compounds were chromatographed on a C18 Novapak column at 250 nm, with a mobile phase of acetonitrile-10 mM ammonium acetate buffer (pH 6.7) (45:55, v/v). Nitrazepam was used as the internal standard. For both drugs, the assay was linear up to 500 micrograms/l, and the detection limits were 20 and 10 micrograms/l for droperidol and flunitrazepam, respectively, and their observed levels in haemodilution samples were 93 +/- 82 micrograms/l and 76 +/- 107 micrograms/l, respectively. Some of the values for flunitrazepam were higher than the minimal efficient concentration, defined as the plasma level observed at the time of the patient wakening from anaesthesia (12 +/- 4 micrograms/l). According to our results, haemodilution sampling can be performed before induction of anaesthesia. When the blood is collected after the anaesthetic induction, it seems necessary to determine levels of the two drugs in haemodilution samples to avoid side-effects. PMID- 8468386 TI - Assay of deoxy-deazapurines in DNA by 3'-phosphorylation and two-dimensional thin layer chromatography. AB - Deoxy-deazapurines (deaza-dNMPs) are incorporated into cellular DNA after administration of anti-neoplastic, anti-viral, or anti-parasitic chemotherapy. Deaza-dNMPs are stable purine analogues and can be detected via 32P-labeling cold DNA. Assay of analogue incorporation and normal base composition is carried out by radiolabeling DNA with all four deoxynucleotides (dNMPs) through nick translation. 3'-Monophosphate digest radiolabels representative dNMPs and deaza dNMPs. Separation occurs in two-dimensional polyethyleneimine-cellulose thin layer chromatography, which resolves all dNMPs. The technique was applied to human placental and calf thymus DNA, control and altered calf thymus DNA with cold stoichiometric replacement of deaza-dNMPs to include deoxy-deazaadenosine, deoxy-deazaguanosine, and deoxy-deazainosine. Scintillation detection and densitometry both accurately reflect dNMP content. This technique easily and quickly quantifies the low-molecular-mass deaza-dNMP analogues in DNA. Deaza-dNMP uptake into DNA may reflect clinical chemotherapeutic efficacy and host toxicity. The assay may therefore serve as an early biochemical dosimeter of drug effect and resistance. PMID- 8468387 TI - Determination of 3-methylflavone-8-carboxylic acid, the main metabolite of flavoxate, in human urine by capillary electrophoresis with direct injection. AB - The effects of tetraalkylammonium salts and sodium dodecyl sulphate on the migration behaviour of human urinary components and other negatively charged or neutral solutes were investigated. The sulphate acted mainly on hydrophobic and positively charged substances, whereas the ammonium salts acted mainly on negatively charged solutes. By choosing the components of the eluent carefully, the free and conjugate forms of 3-methylflavone-8-carboxylic acid (MFA) in human urine, the major metabolites of flavoxate, could be simultaneously determined without pretreatment, using fenprofen as an internal standard. The calibration curve of MFA was linear in the range 1-50 micrograms/ml and the detection limit was 0.2 microgram/ml, which covered the urine levels encountered in pharmacokinetic studies. The intra-day and inter-day precisions of the method, expressed as the relative standard deviation, were less than 2 and 3%, respectively. This method was successfully applied to an excretion study of MFA in eight healthy volunteers, and the results were in agreement with data in the literature obtained by gas chromatography. PMID- 8468388 TI - Improved thin-layer chromatographic separation of 32P-postlabeled DNA adducts. AB - DNA adducts represent the putative initiating event in the chemical carcinogenesis process. 32P-Postlabeling is one of several assays which have been developed for the sensitive detection of DNA adducts. An integral part of the 32P postlabeling assay is the separation of adducted nucleotides by multidirectional, multisolvent, anion-exchange polyethyleneimine-cellulose thin-layer chromatography. Standard since the introduction of this assay has been the use of high-salt, high-urea solvents for the resolution of adducts during the D3 and D4 phases of the chromatography. Urea solvents are able to separate adducts resulting from a number of chemicals, however, they are time-consuming, retain a lot of background noise, may push adducts into inadequately resolved diagonal radioactive zones, and may not separate adducts of similar structure. In this study we introduce the use of a dilute ammonium hydroxide solvent for D4 chromatography and compare it to other standard solvents such as lithium chloride Tris.HCl-urea, sodium phosphate-Tris.HCl-urea, and isopropanol-4 M ammonium hydroxide for adduct separation, resolution, recovery, retention of background noise, and chromatography development time. We found that 0.2 M ammonium hydroxide worked well for the recovery, separation, and resolution of a wide array of adducts derived from highly lipophilic polycyclic aromatic hydrocarbons and aromatic amines. In addition, this solvent required much less time (< 1/4) as compared to the other solvents and more importantly allowed the separation of adducts which otherwise comigrated and were not visible when using the other three D4 solvents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468389 TI - Determination of nicotine and its main metabolites in urine by high-performance liquid chromatography. AB - Nicotine and its main metabolites (cotinine, trans-3'-hydroxycotinine, trans-3' hydroxycotinine glucuronide, nicotine-1'-N-oxide and 3-pyridylcarbinol) were analysed in urine after liquid-liquid extraction by high-performance liquid chromatography using norephedrine as internal standard, ultraviolet detection at 260 nm and scanning ultraviolet spectra with a photodiode-array detector. The conjugated trans-3'-hydroxycotinine was determined after enzymatic hydrolysis. Specific determination of 3-pyridylcarbinol was also carried out. Owing to its good selectivity, sensitivity and reproducibility, the method was applied to the analysis of urine samples from smokers and non-smokers. The results obtained suggest that the urinary markers used to assess active smoking or exposure to environmental tobacco smoke must be not only nicotine and cotinine, but also their main free and conjugated metabolites. PMID- 8468390 TI - High-performance liquid chromatographic assay for two rifamycin-derived hypocholesterolemic agents in liver and biological fluids. AB - CGP 43371 (compound I), a mono-pivaloyl oxazole derivative of a 3-piperazino rifamycin, has been in clinical trials as a potential hypocholesterolemic agent. A reversed-phase high-performance liquid chromatographic (HPLC) assay was developed using a C18 column and a gradient solvent system of methanol-0.1 M sodium acetate, pH 4.5, at a flow-rate of 1 ml/min. The compound and internal standard (rifampicin) were detected by their ultraviolet absorption at 254 nm. Isolation of the compounds from plasma and liver homogenates was accomplished by precipitation of proteins with acetonitrile, followed by evaporation under nitrogen and reconstitution in methanol. Bile, lymph and urine were injected onto the HPLC column without pretreatment. Calibration curves were linear (r > 0.999) over the concentration range 0.25-20.0 micrograms/ml. The assay procedure was also applicable to other rifamycin derivatives and was able to distinguish between molecular species containing small differences in functionality. PMID- 8468391 TI - Determination of boldine in plasma by high-performance liquid chromatography. AB - A sensitive method for the determination of boldine in blood plasma is described. The procedure involves a direct pH-buffered chloroform extraction of boldine from blood plasma, followed by its assay under isocratic conditions by HPLC with UV detection. The extraction recovery is excellent, and sensitivity and precision of the method are very high, when applied to plasma samples containing pharmacologically relevant concentrations of boldine. PMID- 8468392 TI - Immunoaffinity isolation of the sulfate conjugate of 4'-hydroxypropranolol from plasma. AB - Selective extraction of sulfate conjugates of basic drugs from biological matrices has been difficult because of their highly polar nature. Immunoaffinity isolation may be the best solution to this analytical problem. This was tested for a model compound, the metabolite 4'-hydroxypropranolol sulfate (HOPS), which was effectively extracted from plasma by a column containing antibodies to the parent drug propranolol. The specificity was very high, giving little interference from the biological material in subsequent high-performance liquid chromatographic analysis with fluorometric detection. The method for HOPS was highly reproducible and provided a sensitivity of 1 ng/ml plasma. The technique was applied to measurements of HOPS in plasma after therapeutic doses of propranolol as well as to the individual enantiomers after chiral derivatization. PMID- 8468393 TI - Rapid and sensitive pre-column extraction high-performance liquid chromatographic assay for propofol in biological fluids. AB - A completely automated high-performance liquid chromatographic system is described for the determination of the phenolic anaesthetic propofol. The method is based on pre-column extraction in a closed system allowing direct injection of biological samples without any sample pretreatment. The assay is sensitive (limit of quantification is 5 ng/ml serum), reliable (the variability within a series is 2%) and rapid (results are available after 6 min). PMID- 8468394 TI - Assay of artelinic acid in serum by high-performance liquid chromatography. AB - A simple and rapid high-performance liquid chromatographic method with UV detection for the determination in serum of the antimalarial artelinic acid is described. Artelinic acid is a water-soluble semi-synthetic derivative of artemisinin (or Qinghaosu), which is the parent compound of a completely new class of antimalarials with great potential value. Calibration curves of artelinic acid in serum from 0.5 to 50 micrograms/ml were found to be linear, and the extraction recovery was ca. 70% from rabbit serum and 45% from bovine and human serum. The detection limit of the method was 50 ng/ml when 250 microliters of serum were processed. Spiked samples (rabbit serum) proved to be stable for at least 43 days on storage at -20 degrees C. The method has been used for the analysis of ca. 400 samples in a pharmacokinetic study. About 50 samples can be processed in half a day. PMID- 8468395 TI - Methodological commentary on the analysis of metrifonate and dichlorvos in biological samples. PMID- 8468396 TI - 1993 International Chromatography Guide. PMID- 8468397 TI - Embryonic development of rat sympathetic preganglionic neurons: possible migratory substrates. AB - Spinal somatic and autonomic (sympathetic preganglionic) motor neurons are generated synchronously and, subsequently, migrate from the ventricular zone together to form a common primitive motor column. However, these two subsets of motor neurons ultimately express several phenotypic differences, including somal size, peripheral targets, and spinal cord locations. While somatic motor neurons remain ventrally, autonomic motor neurons (AMNs) move both dorsally and medially between embryonic days 14 and 18, when they approximate their final locations in spinal cord. The goal of the present investigation was to determine the potential guidance substrates available to AMNs during these movements. The dorsal translocation was studied in developing upper thoracic spinal cord, because, at this level, the majority of AMNs are located dorsolaterally. Sections were double labeled by ChAT (choline acetyltransferase) and SNAP/TAG-1 (stage-specific neurite associated protein/transiently expressed axonal surface glycoprotein) immunocytochemistry to visualize motor neurons and the axons of early forming circumferential interneurons, respectively. Results showed that during the developmental stage when AMNs translocated dorsally, SNAP/TAG-1 immunoreactive lateral circumferential axons were physically located along the borders of the AMN region, as well as among its constituent cells. These findings indicate that lateral circumferential axons, as well as the SNAP/TAG-1 molecules contained upon their surfaces, are in the correct spatial and temporal position to serve as guidance substrates for AMNs. The medial translocation was studied in developing lower thoracic-upper lumbar spinal cord, because, at this level, more than half of the AMNs are medially located. Sections were double-labeled by ChAT and vimentin immunocytochemistry to visualize motor neurons and radial glial fibers, respectively. Observations on consecutive developmental days of the medial translocation revealed that AMNs were aligned with parallel arrays of radial glial fibers. Thus, the glial processes could serve as guides for the AMN medial movement. Future experimental analyses will examine whether circumferential axons and radial glial fibers are in fact functioning as migratory guides during AMN development, and, if so, whether specific surface molecules on these guides trigger the subsequent differentiation of AMNs. PMID- 8468398 TI - Axonal regeneration is associated with glial migration: comparison between the injured optic nerves of fish and rats. AB - The central nervous systems of mammals and fish differ significantly in their ability to regenerate. Central nervous system axons in the fish readily regenerate after injury, while in mammals they begin to elongate but their growth is aborted at the site of injury, an area previously shown to contain no glial cells. In the present study we compared the ability of glial cells to migrate and thus to repopulate the injured area in fish and rats, and used light and electron microscopy in an attempt to correlate such migration with the ability of axons to traverse this area. One week after the optic nerve was crushed, both axonal and glial responses to injury were similar in fish and rat. In both species glial cells were absent in the injured area (indicated by the disappearance of glial fibrillary acidic protein and vimentin immunoreactive cells from the site of injury in rat and fish, respectively), while at the same time axonal growth, indicated by expression of the growth-associated protein GAP-43, was restricted to the proximal part of the nerve. In fish, 2 weeks after the crush, GAP-43 staining (i.e., growing axons) was seen at the site of injury, in association with migrating vimentin-positive glial cells. One week later the site of injury in the fish optic nerve was repopulated by vimentin-positive glial cells, and GAP 43-positive axons had already traversed the site of injury and reached the distal part of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468399 TI - First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system. AB - A phagocytic cell system of hemopoietic origin exists in the early avian embryo (Cuadros, Coltey, Nieto, and Martin: Development 115:157-168, '92). In this study we investigated the presence of cells belonging to this system in the central nervous system (CNS) of chick and quail embryos by using both histochemical staining for acid phosphatase and immunolabelling with antibodies recognizing cells of quail hemangioblastic lineage. The origin of these cells was traced in interspecific chick-quail yolk sac chimeras. Hemopoietic cells were detected within the CNS from developmental stage HH15 on, and steadily increased in number at subsequent stages. Analysis of yolk sac chimeras revealed that most of these cells were of yolk sac origin, although some hemopoietic cells of intramebryonic origin were also found in the CNS. Immunocytochemical, histochemical, and ultrastructural characterization allowed us to identify hemopoietic cells in the CNS as macrophages. These cells were consistently found in the brain vesicles and spinal cord, appearing (1) between undifferentiated neuroepithelial cells at dorsal levels of the CNS; (2) in areas of cell death; (3) in the marginal layer in close relationship with developing axons; (4) in large extracellular spaces in the subventricular layer; (5) on vascular buds growing through the marginal and subventricular layers; and (6) in the ventricular lumen. Macrophages in different locations varied in morphology and ultrastructure, suggesting that in addition to their involvement in phagocytosis, they play a role in other processes in the developing CNS, such as axonal growth and vascular development. The first macrophages migrate to the CNS independently of its vascularization, apparently traversing the pial basal lamina to reach the nervous parenchyma. Other macrophages may enter the CNS together with vascular buds at subsequent stages during CNS vascularization. PMID- 8468400 TI - Cerebellar nuclear projections from the basilar pontine nuclei and nucleus reticularis tegmenti pontis as demonstrated with PHA-L tracing in the rat. AB - Small iontophoretic placements of the orthogradely transported axonal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were made in portions of the basilar pontine nuclei (BPN) or nucleus reticularis tegmenti pontis (NRTP) to determine if these cell groups provide projections to the cerebellar nuclei (CN) in the rat and if so, to visualize the morphology of the axons and terminals and illustrate any topographical organization in this system. Axons that originated from BPN or NRTP neurons and contained PHA-L were visualized by an immunohistochemical procedure that involved sequential incubation of tissue sections with goat anti PHA-L antibody, biotinylated rabbit anti-goat immunoglobulin, and a biotin-avidin peroxidase conjugate. Following injections of PHA-L restricted to ventral and medial portions of the BPN, labeled fibers were observed in the brachium pontis, the white matter dorsal to the CN, and to a lesser extent, in the white matter of the parafloccular stalk. Labeled preterminal axons entered the CN and gave rise to beaded axons that arborized primarily within dorsal portions of the lateral, interposed, and medial cerebellar nuclei. Injections of PHA-L restricted to either lateral portions of the BPN or ventrolateral regions of NRTP produced labeled fibers in the cerebellum that most frequently involved the parafloccular stalk and ventral portions of the CN. In contrast, dorsomedial NRTP injections resulted in the presence of labeled fibers both in the dorsal cerebellar white matter and the parafloccular stalk as well as dorsal and ventral portions of the CN. With the exception of the rostral and medial territory of interpositus anterior which received very sparse input, all portions of each CN subdivision seemed to exhibit some degree of terminal labeling. The density of labeled axon terminals in the CN appeared to be somewhat greater in the NRTP-injected cases compared to BPN-injected animals. These observations indicate that in the rat, both the BPN and NRTP contain neurons whose axons distribute to the CN. It is likely that most of the axons which project to the CN are collaterals of fibers that continue into the cerebellar cortex as mossy fibers but confirmation of this point must await further investigation. In light of the extensive projections from the cerebral cortex to the BPN and NRTP, this axonal system provides the cerebral cortex with a relatively direct route of access to the CN via one synapse in the BPN or NRTP. PMID- 8468401 TI - Heterogeneity and selectivity of the degeneration of cholinergic neurons in the basal forebrain of patients with Alzheimer's disease. AB - Cholinergic neurons were studied by immunohistochemistry, with an antiserum against choline acetyltransferase (ChAT), in the basal forebrain (Ch1 to Ch4) of four patients with Alzheimer's disease (AD) and four control subjects. ChAT positive cell bodies were mapped and counted in Ch1 (medial septal nucleus), Ch2 (vertical nucleus of the diagonal band), Ch3 (horizontal nucleus of the diagonal band) and Ch4 (nucleus basalis of Meynert). Compared to controls, the number of cholinergic neurons in AD patients was reduced by 50% on average. The interindividual variations in cholinergic cell loss were high, neuronal loss ranging from moderate (27%) to severe (63%). Despite the small number of brains studied, a significant correlation was found between the cholinergic cell loss and the degree of intellectual impairment. To determine the selectivity of cholinergic neuronal loss in the basal forebrain of AD patients, NPY immunoreactive neurons were also investigated. The number of NPY-positive cell bodies was the same in controls and AD patients. The results (1) confirm cholinergic neuron degeneration in the basal forebrain in AD and the relative sparing of these neurons in some patients, (2) indicate that degeneration of cholinergic neurons in the basal forebrain contributes to intellectual decline, and (3) show that, in AD, such cholinergic cell loss is selective, since NPY positive neurons are preserved in the basal forebrain. PMID- 8468402 TI - Immunocytochemical localization of atrial natriuretic factor (ANF)-like peptides in the brain and heart of the treefrog Hyla japonica: effect of weightlessness on the distribution of immunoreactive neurons and cardiocytes. AB - The localization of atrial-natriuretic factor (ANF)-like immunoreactivity was investigated in the brain and heart of the treefrog Hyla japonica by the indirect immunofluorescence technique. Concurrently, the effect of weightlessness on the distribution of ANF-containing neurons and cardiocytes was studied in frogs that were sent into space for 9 days on the space station "MIR." In control animals, the amygdala contained the most prominent group of ANF-immunoreactive cells and fibers. ANF-positive neurons and nerve processes were also detected in other areas of the telencephalon such as the nucleus olfactorius, the pallium mediale, and the striatum. In "space frogs," the intensity of labeling of the amygdala and nucleus olfactorius was similar to that seen in control animals. In contrast, the pallium and the striatum of "space frogs" were totally devoid of positive cell bodies. In the diencephalon, of all animals, numerous ANF-immunoreactive perikarya and fibers were seen in the hypothalamus, the anterior thalamus, the infundibulum, and the median eminence. ANF-positive cell bodies were also noted in the lateral forebrain bundle of control frogs but were absent in "space frogs." The major difference between control and "space frogs" was observed in the posterior nuclei of the thalamus. In "space frogs," the nucleus posterocentralis thalami and the nucleus posterolateralis thalami exhibited large ANF-immunoreactive perikarya, while, in control frogs, these nuclei only contained scarce positive nerve fibers. In the mesencephalon, ANF-positive cell bodies and nerve processes were seen in the nucleus tegmenti mesencephali, the interpeduncular nucleus, and the nucleus cerebelli of all animals. However, stained perikarya were only observed in the nucleus reticularis isthmi of control frogs. In the heart, atrial cardiocytes exhibited intense ANF-like immunoreactivity. ANF-positive myocytes were also detected in the subpericardial region of the ventricle. The density and distribution of the staining were identical in the heart of control and "space frogs." These data support the concept that prolonged exposure to microgravity affects biosynthesis and/or release of ANF-related peptides in discrete regions of the amphibian brain. PMID- 8468403 TI - Synaptophysin immunohistochemistry reveals inside-out pattern of early synaptogenesis in ferret cerebral cortex. AB - Synaptogenesis in the ferret cerebral cortex was examined from the day of birth to adulthood with an antibody against synaptophysin at the light and electron microscopic levels. Due to the premature birth of ferrets, the generation of cells destined to the upper cortical layers and their subsequent migration to their final positions in the cortical plate are largely postnatal events. Throughout the newborn ferret cerebral cortex, a high amount of synaptophysin immunoreactivity was present within the marginal zone and subplate region. Staining was also conspicuous within the forming cortical plate. The typical layering pattern of synaptophysin immunoreactivity in the developing cortical plate correlated with the migration pattern of cortical neurons. The synaptic density was lowest directly below the marginal zone, where the youngest neurons just stopped their migration. Below this zone, the density of the synaptic staining increased gradually toward lower (and older) cortical plate layers. As the cortex expanded, the synaptophysin immunoreactivity pattern closely followed the expansion, suggesting that synapses were formed in a given layer shortly after the cells migrating to this layer reached their final position. As soon as cell migration had finished, the entire cortical plate contained dense synaptophysin immunoreactivity, in a pattern similar to that observed in the adult animal. During cortical development, a rostrocaudal and a laterodorsal gradient of synaptogenesis was observed. At any given time, rostral and lateral regions of the cerebral cortex were more advanced in their development than caudal and dorsal regions. Electron microscopic examination of synaptophysin immunoreactivity in the developing cerebral cortex of ferrets confirmed that labeling was solely associated with synaptic vesicles. These vesicles were typically, but not exclusively, confined to synaptic boutons. Especially around the end of the first postnatal week, long fiber profiles loaded with synaptic vesicles were occasionally detected. As some of these fibers also showed en passant synapses along their course, we concluded that synaptic vesicle labeling may be reliably used to study synaptogenesis at the light microscopic level. A systematic analysis of samples from postnatal days 0 and 7 corroborated this conclusion, showing that synaptic profile distribution completely matched the distribution of synaptophysin immunoreactivity seen in the light microscope. In conclusion, synaptogenesis begins as soon as migratory cells reach their final position in the cortical plate. As long as cell migration continues, synaptogenesis is under the constraints of neurogenesis, following its gradients. PMID- 8468404 TI - Chronic peripheral nerve section results in a rearrangement of the central axonal arborizations of axotomized A beta primary afferent neurons in the rat spinal cord. AB - In order to investigate the reorganization of the neuropil of the dorsal horn following peripheral nerve injury, the central terminal arborizations of 35 A beta primary afferent neurons, chronically injured by a cut and ligation of the sural nerve 6-12 weeks previously, were studied by the intra-axonal injection of horseradish peroxidase. Their morphology was compared to 13 intact sural nerve hair follicle afferents. Following axotomy, three kinds of morphological abnormalities were observed in the collateral arbors of the 26 afferents that were hair follicle-like. Atrophy with thin stem axons and reduced terminal branch patterns with few boutons was seen in 5 afferents. Sprouting of bouton-containing terminals into lamina I and IIo was found in 8 afferents. Finally, abnormal arborization patterns in the deeper laminae were observed in 29% of the collateral arbors. Changes included the loss in some arbors of a flame-shaped appearance, which is characteristic of hair follicle afferents, atypical branching patterns and ventrally directed axons producing wider and deeper arbors, compared to normal. Axotomy also caused a disruption of the normal somatotopic organization of sural nerve A beta afferents. This disruption manifested as a variability in the normally mediolaterally restricted terminal sheet, with a consequent loss of the strict somatotopic register in the rostrocaudal direction. Damage to the peripheral axon of A beta primary afferents induces a structural reorganization of their central terminals in the dorsal horn of the spinal cord, which may modify sensory input to the central nervous system. PMID- 8468405 TI - Deafferentation-induced terminal field expansion of myelinated saphenous afferents in the adult rat dorsal horn and the nucleus gracilis following pronase injection of the sciatic nerve. AB - We have previously demonstrated sprouting of small diameter saphenous afferents, labelled with wheat germ agglutinin conjugated with horseradish peroxidase (WGA HRP) and (HRP), into the sciatic territory of the adult rat superficial dorsal horn following destruction of sciatic afferents by injection of the sciatic nerve with pronase (a combination of proteolytic enzymes). In the present experiments, we examined the response of myelinated saphenous axons, which terminate in lamina I and the deep dorsal horn (laminae III-V) under the same conditions, with the tracer B subunit of cholera toxin conjugated to HRP (B-HRP) which specifically labels myelinated primary afferents when injected into a peripheral somatic nerve. We also examined changes in the nucleus gracilis, another site of sciatic degeneration and a target of saphenous afferents. Four months after injection of the pronase, the area of label determined by measurement of the width of the saphenous territory in lamina III was expanded by 24% on the pronase side. Since there was also expansion throughout the deep dorsal horn, the area measured by tracing the labelled region in transverse sections was actually twice that of the control side, and the intensity of labelling within the traced area increased by 18%. There was no change in grey matter area due to the lesion. The traced area of labelling in the nucleus gracilis increased by 40%, and increased in intensity by 17%. The substantia gelatinosa is not normally supplied by B-HRP-labelled afferents, and there was no expansion of these sprouted saphenous afferents into the gelatinosa. These results indicate that myelinated afferents can sprout as vigorously in lamina I and the deep dorsal horn as the small diameter afferents do in the substantia gelatinosa; that there is no invasion of the substantia gelatinosa by the myelinated afferents at least as long as the small diameter afferents also have the opportunity to sprout; and that primary afferents have the potential to sprout at more than one site of termination, i.e., both the dorsal horn and the dorsal column nuclei. PMID- 8468406 TI - Chiasmatic course of temporal retinal axons in the developing ferret. AB - Recent studies on the distribution of optic axons in the mature visual pathways, as well as on the genesis of their ganglion cells of origin, suggest that the time of axonal arrival at the optic chiasm determines the side of the brain to which a temporal retinal axon will project. The present study has examined this issue directly in fetal ferrets, by determining the projection of the temporal retina at different developmental stages. Fetuses of known gestational age were fixed with paraformaldehyde and subsequently implanted with crystals of the carbocyanine dye, DiI, into either the temporal retina, or into one optic tract. The lipophilic diffusion of the dye within the plasma membrane of the axons revealed the course of temporal retinal fibers through the fetal chiasm, as well as the distribution of ganglion cells across the two retinae projecting to one optic tract. During early fetal stages, the temporal retina extends axons preferentially into the ipsilateral optic tract: the early retinal projection shows a classical partial decussation pattern. During later fetal stages, temporal retinal axons can be traced into both optic tracts, and the distribution of cells with crossed and uncrossed optic axons in the temporal retina is overlapping. These results indicate that the mature decussation patterns of retinal ganglion cell classes are not primarily the consequence of regressive phenomena such as cell death; rather, they are formed as axons navigate the chiasmatic region during development. The differences in decussation pattern between cell classes arise from the fact that the mechanisms producing the segregation of nasal and temporal retinal axons at the chiasm must change as development proceeds. PMID- 8468407 TI - Geometry of the representation of the visual field on the superior colliculus of the wallaby (Macropus eugenii). I. Normal projection. AB - In 13 wallabies (Macropus eugenii, the tammar), microelectrode recordings of the activity of units in the superficial layers of the superior colliculus in response to a flashing light spot were used to make a map of the spatial location of their receptive fields. This article describes the projection of a normal eye to the contralateral colliculus. Ten of the 13 animals had one rotated eye and these projections are analysed in the accompanying paper (James et al., this issue). Units responded briskly to the stimulus at light on and off and had receptive fields about 5 degrees across. The centres of receptive fields from a regular array of recording points on the colliculus were plotted with a perimeter and fitted to a flattened representation of the colliculus according to a spline technique. The visual field of each colliculus extends from 25 degrees ipsilateral to the vertical meridian to 120 degrees temporal contralaterally. The lines of isoazimuth are regularly spaced and parallel and run mediolaterally on the colliculus. The horizon is represented by a line running rostrocaudally and the parallels are more widely spaced near the horizon and become compressed in the superior and inferior fields. The variation of areal magnification factor fits the distribution of density of retinal ganglion cells very well. Anisotropy of the projection means that the increased ganglion cell density of the retinal visual streak is entirely accommodated by magnification in the vertical direction, while the magnification of the azimuthal projection is equal over the whole field. No responses were recorded from the ipsilateral eye even though anatomically there is a direct retinal ipsilateral projection. PMID- 8468408 TI - Geometry of the projection of the visual field onto the superior colliculus of the wallaby (Macropus eugenii). II. Stability of the projection after prolonged rearing with rotational squint. AB - At about the time of eye opening, one eye of seven tammar wallaby pouch young was surgically rotated about the optic axis by approximately 90 degrees. In adulthood the projection of the visual field through the rotated eye onto the contralateral superior colliculus was mapped electrophysiologically. Although apparently distorted, the projection could be coherently re-rotated mathematically to a reasonable copy of the normal projection from the opposite eye of the same animal, including details such as regional variations of the magnification factor. The same was true of three adult animals in which the eye rotation was done after anaesthesia immediately before the electrophysiological mapping. In animals in which the visual field seen through one eye, the other being normal, was rotated for the entire period of visual experience, there was no sign of compensation or rearrangement of the topographic map. Retinocollicular synaptic connections appear unmoved by such discordant visual experience. PMID- 8468409 TI - Adrenalectomy-induced granule cell degeneration in the rat hippocampal dentate gyrus: characterization of an in vivo model of controlled neuronal death. AB - The recent discovery that adrenalectomy results in hippocampal granule cell loss suggested that this phenomenon might be useful as a model of selective, experimentally controlled neuronal death possibly relevant to neurodegenerative disorders. This study was designed to provide a detailed qualitative anatomical description of the phenomenon and to determine whether adrenalectomy-induced dentate granule cell degeneration constitutes a reliable model of selective neuronal death. Silver impregnation staining revealed that granule cell degeneration begins immediately after adrenalectomy and continues for months in both sexes, in young and older adults, and in all strains tested. In one group of 77 adrenalectomized rats, 82% exhibited silver-impregnated granule cells. This phenomenon is extraordinarily selective in that no neurons other than dentate granule cells degenerated after adrenalectomy. There was considerable variability among animals in the number of cells degenerating at a given time-point or in the degree of ultimate cell loss. In the most extreme cases, virtually complete granule cell loss was present throughout approximately 80% of the dentate gyrus. Nissl staining revealed that degenerating granule cells exhibited coalescing of nuclear chromatin into multiple nuclear bodies and pyknosis without accompanying glial swelling. This morphology is distinct from the necrosis caused by other neurotoxic insults and is the subject of the ultrastructural companion paper identifying this type of cell death as apoptosis. Taken together, these results indicate that adrenalectomy reliably initiates an immediate, highly selective, and long-continuing process of hippocampal granule cell degeneration that exhibits morphological features characteristic of apoptosis, rather than necrosis. The possibility that this apoptotic cell death involves a biochemical cascade relevant to programmed cell death and/or neurodegenerative diseases suggests that this model may be valuable for studies of neuronal death and its prevention. Some practical guidelines for use of this model are described. PMID- 8468410 TI - Electron microscopic analysis of adrenalectomy-induced hippocampal granule cell degeneration in the rat: apoptosis in the adult central nervous system. AB - As described in the preceding paper, adrenalectomy triggers hippocampal granule cell degeneration that begins within days after adrenalectomy, continues for months, and is the only apparent cell death anywhere within the brain. At the light microscopic level, granule cell degeneration is characterized by coalescing of nuclear chromatin into numerous spherical bodies. Since the morphology at the light microscopic level resembled the nuclear morphology characteristic of "apoptosis" rather than "necrosis," we undertook this ultrastructural study to determine if adrenalectomy induces the morphological features characteristic of apoptosis. Electron microscopy revealed coalescing of nuclear chromatin, compaction of cytoplasm, and the budding-off of cytoplasmic bodies that were engulfed by glia. Mitochondria, the Golgi apparatus, and rough endoplasmic reticulum appeared relatively normal early in the process of granule cell degeneration when nuclear changes were prominent. Presynaptic terminals innervating degenerating granule cells appeared normal. Electron-dense degeneration of granule cell axon terminals in association with normal postsynaptic elements of CA3 pyramidal cells highlighted the extraordinary selectivity of adrenalectomy-induced granule cell death. Ten weeks after adrenalectomy, astrocytes were filled with abnormally abundant glial fibrils and neuronal debris. This "apoptotic" morphology produced by adrenalectomy was clearly distinct from the "necrotic" granule cell morphology produced by intrahippocampal injection of the neurotoxin volkensin. These results indicate that, in a manner possibly analogous to castration-induced prostate cell death, loss of adrenal hormone triggers a process in dentate granule cells that causes the morphological changes characteristic of "apoptosis." Thus, adrenal steroids may be obligatory growth factors for dentate granule cells and their loss may initiate a selective process in the mature brain that is unique or that may normally occur only in the developing brain. PMID- 8468411 TI - Organum vasculosum laminae terminalis (OVLT) in rabbit and rat: topographic studies. AB - The microcirculation and fine structure of the rabbit and rat organum vasculosum laminae terminalis (OVLT) were examined by light microscopy and scanning and transmission electron microscopy. In both animals, the microcirculation is composed of a superficial and a deep vascular bed but the system is more complex and extensive in the rabbit. This was particularly true of the deep vascular bed. In the rabbit, the deep bed is composed of fenestrated capillaries, which are arranged in glomerular tufts surrounded by very wide perivascular spaces (PVS). In contrast, the deep vascular bed of the rat OVLT usually consists of only one or two small vessels. These are either fenestrated and surrounded by a PVS or lined by continuous endothelium with only a few fenestrae and without a dilated PVS. A corresponding difference was seen in the contours of the ventricular surface. It is much more irregular in the rabbit than in the rat and numerous bulges reflect the underlying vascular tufts and pockets of PVS in the rabbit. Supraependymal cells are present in both species and two sizes of them occur in the rabbit. The results demonstrate that the microcirculation of the OVLT is more elaborate and more highly developed in the rabbit than in the rat. We suggest that this might result in a different neurohemal microenvironment and, ultimately, in functional differences. PMID- 8468412 TI - Neuroanatomical distribution and binding properties of saxitoxin sites in the rat and turtle CNS. AB - Since saxitoxin (STX) binds to voltage-sensitive sodium channels and blocks their function, it has been widely used in the study of these channels. There is, however, limited information on STX binding properties and the neuroanatomical distribution of the Na+ channel as a function of brain region in the rat and in lower vertebrates such as the turtle. In the present study, we used a broad range of 3H-STX concentration (up to 64 nM) to examine saturation profiles and density distribution in both adult rat and turtle brains. We found that (1) STX sites do not vary greatly in affinity (most Kds = 2 to 5 nM) in various regions of the adult rat brain; (2) STX binding distribution was very heterogeneous in the rat with much higher density in the cortex, hippocampus, amygdala, and cerebellum than in the brainstem and spinal cord; (3) STX sites are mostly localized in layers made mostly of neurons with low density in white matter; and (4) turtle brain STX sites had similar binding properties, but its brain had much fewer STX sites than the rat, especially in the cerebellum and rostral areas such as the cortex. We conclude that (a) adult brain sodium channels have similar STX binding affinity in spite of the existence of multiple sodium channel subtypes; (b) the brainstem is very different from rostral brain areas in channel density; and (c) the turtle brain has a much lower sodium channel density than the rat brain. PMID- 8468413 TI - Quantitative synaptology of functionally different types of cat medial gastrocnemius alpha-motoneurons. AB - The aim of this ultrastructural investigation was to study quantitatively the synaptology of the cell bodies and dendrites of cat medial gastrocnemius (MG) alpha-motoneurons of functionally different types. In electrophysiologically classified and intracellularly HRP-labelled MG alpha-motoneurons of the FF (fast twitch, fatigable), FR (fast twitch, fatigue resistant) and S (slow twitch, very fatigue resistant) types, the synaptic covering of the soma as well as that of dendritic segments located within 100 microns and at 300, 700, and 1,000 microns distance, respectively from the soma, was analyzed. The synaptic boutons were classified into the L-(apposition length > 4 microns) and S-types (< 4 microns) with spherical synaptic vesicles, and the F-type with flat or pleomorphic synaptic vesicles. The length of apposition towards the motoneuron membrane was measured for each bouton profile. Approximately 1,000 boutons contacted the soma and a similar number of boutons contacted the proximal dendrites within 50 microns from the soma. The number of dendritic boutons was larger at the 300 microns distance than at the 100 and 700 microns distances. The three types of motoneurons showed similar values for percentage synaptic covering and synaptic packing density in the proximal dendrites, while in the most distal dendritic regions the S motoneurons had more than 50% higher values for percentage covering, packing density and total number of boutons. The S motoneurons also exhibited a larger preponderance of F-type boutons on the soma. The ratio between the F- and S-types of boutons decreased somatofugally along the dendrites in the type FF and FR motoneurons, while in the S motoneurons it remained fairly constant. PMID- 8468414 TI - The cutaneous histopathology of chemotherapeutic reactions. AB - The histological diagnosis of chemotherapy-induced cutaneous reactions is a difficult problem for the dermatopathologist. The initial effort should be directed towards obtaining as much clinical history as possible since the provided information is often incomplete and clinical correlation is usually required. The biopsy should be examined in a systematic fashion to assess the presence of damage to specific cutaneous structures. A recommended approach is to initially examine the epidermis and then proceed to hair follicles, eccrine sweat glands, vessels and dermis. The degree and pattern of damage will usually indicate whether or not a cytotoxic reaction is present. The intensity, pattern, and components of the inflammatory response should be assessed since they provide clues to whether a hypersensitivity reaction or immunomodulating chemotherapeutic reaction is present. In addition to the possibility of a chemotherapeutic reaction, the dermatopathologist must also consider the possibility of an infection since the host is usually immunocompromised and must also exclude the presence of a residual malignancy. After examination of the biopsy specimen and determination of the pathologic process or precesses, the observed findings should be correlated with the clinical history before rendering an interpretation. PMID- 8468415 TI - Plexiform and other unusual variants of palisaded encapsulated neuroma. AB - Palisaded, encapsulated neuroma (PEN) has been described as a predominantly solitary, nodular tumor; plexiform or multinodular growth patterns have not been reported in detail. We reviewed 55 PEN in order to evaluate: 1) the predominant growth patterns; 2) features that may indicate previous trauma; and 3) association with acne-like changes. Sixteen cases (29%) had growth patterns other than the solitary, nodular type. These patterns were: a) plexiform (7/16), b) multinodular (5/16), and c) fungating (4/16). Other unusual features included evidence of trauma, i.e., fibrosis, myxoid change, chronic inflammation (5/16), partially incomplete capsule (6/16), and association with acne-like features (13/16). These results suggest that: 1) plexiform or multinodular growth patterns occur relatively often in PEN; 2) some changes indicate a possible histogenetic relation to traumatic neuroma, probably via secondary traumatization; 3) a high frequency of association with acne-like changes which could imply, but does not prove, an acne-induced histogenesis; and 4) the differential diagnosis of cutaneous plexiform lesions should include PEN. PMID- 8468416 TI - Trichilemmal carcinoma: review of 8 cases. AB - Clinical and histological data from 8 trichilemmal carcinomas are reviewed. The tumors occurred mainly on sun-exposed skin of the face of elderly people as small solitary, frequently ulcerated nodules. Histologically, they consisted of multilobulate, infiltrative growths, connected to the epidermis and pilosebaceous structures and showing features reminiscent of the outer root sheath of the hair follicle. The presence of lobules of clear, glycogen-rich cells with peripheral palisading, hyaline basement membranes, trichilemmal keratinization, and abortive follicular sheaths and the absence of ductal or acinar differentiation allow distinction from other clear cell tumors of the skin. Although the histological picture suggests a high-grade malignant neoplasm, trichilemmal carcinoma has an indolent course. No recurrence or metastases have been observed. PMID- 8468417 TI - Further validation of the prognostic model for stage I malignant melanoma based on tumor progression. AB - Prediction of long-term survival for clinical stage I malignant melanoma and guidance of therapy has long relied upon assessment of tumor thickness. This parameter is a strong, but not infallible predictor of prognosis. Clark et al. have developed a prognostic model based upon the concept of tumor progression and the evaluation of six readily assessable clinical and histologic attributes. They report the most accurate prediction of long-term survival of any prognostic method available for melanoma (100% accurate for radial-growth-phase and 84.1% accurate for vertical-growth-phase melanomas). This model was developed and validated via study of a patient population which largely resided in the northeastern portion of the United States. We report additional validation of this model using a data base of 55 patients from a different geographic location (North Carolina) and have observed virtual identity in the accuracy of predicting 8-year survival for radial-growth-phase (100%) and vertical-growth-phase (85.1%) melanomas. Twenty per cent of these cases were randomly selected and subjected to re-evaluation for prognosis with extremely good precision obtained in the prognostic prediction. PMID- 8468418 TI - Immunelectron microscopic localization of cathepsin B in human exocrine glands. AB - The distribution of the lysosomal enzymes cathepsin B, lysozyme, chymotrypsin, and neutrophil elastase was examined in eccrine, apocrine, and sebaceous glands using a postembedding immunogold labeling procedure. Various amounts of cathepsin B were detected in all glands. Lysozyme, however, was detected in apocrine glands only. The other two lysosomal enzymes were not detectable immunologically. In apocrine and eccrine glands, anti-cathepsin B antibody labeled all secretory granules. In sebaceous glands, only the peripheral layer of cells showed immunological activity for cathepsin B. In apocrine glands, granules containing remnants of cristae were more intensively labeled than those lacking cristae which supports the assumption that both granules are derived from mitochondria by acquiring lysosomal enzymes. The enzymes convert mitochondria to granules with cristae and finally to granules without cristae. Thus the difference in morphology is part of a spectrum of the degradation of mitochondria to granules. PMID- 8468419 TI - Nodular fasciitis of the dermis. AB - We describe the second reported patient with nodular fasciitis involving the dermis. Our case was morphologically a typical example of nodular fasciitis, but was distinctive by its cutaneous location and recurrence. As in the first reported case, the unexpected dermal involvement caused diagnostic difficulty, despite a typical histology. PMID- 8468420 TI - Basal cell carcinoma with monster cells. AB - A case of basal cell carcinoma with "monster cells" is reported. Clinically, the lesion presented as a red nodule on the forearm of a 58-year-old male. The histologic picture was striking, with large, "monstrous" nuclei scattered throughout a well defined nodule. Basal cell carcinoma with monster cells appears to represent a histologic variant of nodular basal cell carcinoma. The prognostic significance of the monster cells remains to be established. PMID- 8468421 TI - Intravascular immunoglobulin crystalloids in monoclonal cryoglubulinemia associated dermatitis: ultrastructural findings. AB - A 46-year-old woman developed polyarthritis, purpuric skin rashes, nasal septal perforation and marginal furrowing of corneas in 1980. Monoclonal IgG, kappa cryoglobulinemia was found in the patient's serum. No underlying lymphoproliferative disorder has been found in ten years since her original diagnosis. In 1991, she developed palpable purpura on both lower extremities with subsequent necrosis and ulceration. A skin biopsy revealed fibrin thrombi within capillaries in the papillary dermis, and immunofluorescence studies showed IgG and light chain kappa within the fibrin thrombi. An electron microscopy study showed intravascular immunoglobulin crystalloid structures with a mean diameter of 80.3A degrees (8.03 nm), mixed with fibrin and red blood cells. The exclusive vascular location of these crystalloids may have implication in the pathogenesis of skin lesions. PMID- 8468422 TI - Apocrine nevus: light microscopic, immunohistochemical and ultrastructural studies of a case. AB - The apocrine nevus (AN) is a rare tumor occurring in the upper chest and the axilla. We report a case of a AN in a 33-year-old female occurring unilaterally. The presenting complaint related to tenderness and swelling in the right axilla. The initial impression was hidradenitis suppurativa. The gross specimen revealed the presence of irregular thickening just beneath the dermal subcutaneous interface. Microscopically the lesion was composed of mature apocrine glands with apical snouts. The glands were arranged in lobules divided by thin fibrous septa. Immunohistochemical studies revealed the following profile in the glandular epithelium: positive low molecular weight cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein reactivity and negative high molecular cytokeratin and S-100 protein reactivity. Carcinoembryonic antigen reactivity was found in the duct epithelium. Ultrastructural studies revealed cells lining the lumen of the glands with a concentration of granules in the apical region and light and dark granules. These findings support the previously described light microscopic observations and provide unreported ultrastructural studies in this rare tumor. PMID- 8468423 TI - Myxoid change in decidualized scar endometriosis mimicking malignancy. AB - A case of cesarean scar endometriosis with massive decidualization is presented. The 25-year-old patient had an extensive, ulcerated lesion that mimicked malignancy microscopically due to myxoid change with alveolar patterns reminiscent of some soft tissue sarcomas, signet ring-like cells similar to mucin producing carcinoma, and pseudoinfiltration of the fascia. The myxoid tissue was positive for acid mucopolysaccharides but negative with PAS. Decidual cells were vimentin positive and keratin negative. No atypia or mitoses were seen. The pseudoinfiltrative aspect was due to abundant extracellular matrix that separated the fascicles of the fascial tissue. There was a metaplastic decidual "proximity effect" in the surrounding, unaffected dermis, which may be responsible for the expansile features of the lesion. This case exemplifies the differential diagnosis of myxoid endometriosis with malignant conditions of the skin. PMID- 8468424 TI - Vascular variant of palisaded encapsulated neuroma. PMID- 8468426 TI - Parallel lives, deaths, questions. PMID- 8468425 TI - Plaque-like dermal fibromatosis/dermatomyofibroma. PMID- 8468427 TI - Peripheral effects of sex steroids: implications for patient management. AB - Sex steroids--estrogens, progesterone, and testosterone and other androgens--have effects on the anatomy and physiology of many nonreproductive organ systems. These changes can influence the sex ratio of certain diseases. They also affect the "normal range" for certain parameters, and data from men often do not apply to normal female physiology. Sex steroids also affect the response to certain toxins, pharmacologic agents, and other therapies. Replacement sex steroid therapy and oral contraceptives may affect these processes differently than natural hormones do. The normal monthly changes of female hormones can also affect the severity of many conditions and may change the response to therapy in certain conditions, such as asthma or control of diabetes. This paper reviews the data on the effects of sex hormones on normal and pathologic human physiology and examines the therapeutic implications of these findings. PMID- 8468428 TI - Women in surgery. PMID- 8468429 TI - Perceptions of the gender fairness of the medical education environment. AB - Many medical institutions are making an effort to create "gender-fair" environments. Perceptions of the current state of the environment may have implications for progress toward this goal. We surveyed faculty, housestaff, and medical students at the University of Virginia School of Medicine (UVASOM) to determine their perceptions of the status of women at that institution. The results showed that women perceived their environment as significantly more inequitable and sexist than their male counterparts did. Women faculty perceived significantly more inequity and sexism than women housestaff or students. Comments from both women and men at UVASOM focused on the need to eliminate discrimination of all kinds and to recruit more women faculty as leaders, mentors, and role models. The UVASOM is now implementing recommendations that should significantly reduce the discrepancy in perceptions of its environment. PMID- 8468430 TI - War crimes of the 90s: rape as a strategy. PMID- 8468431 TI - RIMAs in subtypes of depression: focus on moclobemide. Third International Symposium, Vienna, 29-31 March 1992. PMID- 8468432 TI - RIMA--a new concept in the treatment of depression with moclobemide. AB - Moclobemide, a specific reversible inhibitor of monoamine oxidase that shows a preference for the A isoenzyme, has been developed as a new antidepressive agent. Unlike earlier generation monoamine oxidase inhibitors, moclobemide is devoid of any clinically significant tyramine interaction, thus making dietary restrictions during therapy unnecessary. In comparative trials, moclobemide has been found to be superior to placebo and similar to imipramine, clomipramine, and amitriptyline in clinical efficacy. Long-term trials involving moclobemide therapy for up to one year have indicated that antidepressant efficacy can be maintained for this period. Tolerance is good and is significantly better than for tricyclic antidepressants. In addition, unlike the tricyclic antidepressants, overdoses of moclobemide do not appear to be life-threatening. PMID- 8468434 TI - The role of moclobemide in endogenous depression: a survey of recent data. AB - Earlier studies demonstrated that moclobemide has good efficacy as an antidepressant. Its efficacy was comparable to reference antidepressants, both in endogenous and non-endogenous depression. A meta-analysis was performed of recent data from more than 2000 patients who had participated in double-blind trials with moclobemide and comparison drugs. Based on HAMD-17 baseline scores, the sample was divided into three groups according to the severity of depression. In all three, moclobemide was as effective as comparison drugs, both in endogenous and non-endogenous depression. The antidepressant efficacy of both moclobemide and reference drugs was more pronounced in endogenous than in non-endogenous depression, whatever the severity. PMID- 8468433 TI - Moclobemide--placebo-controlled trials. AB - In this paper, three placebo-controlled trials of moclobemide, and four three-way comparison trials of moclobemide, placebo and one of the standard tricyclic antidepressants, imipramine, clomipramine, or amitriptyline, are reviewed. The results of the placebo-controlled trials indicate that about twice as many of the patients receiving moclobemide showed a marked improvement during a four-week treatment period, as compared with patients receiving placebo. Of the three-way trials, two studies indicated that the efficacy of moclobemide was significantly greater than that of placebo and similar to that of other antidepressants (imipramine or amitriptyline). Tolerance of moclobemide was good and better than that of the tricyclic antidepressants. In the other three-way comparison trials, the differences in efficacy between the placebo, moclobemide, and the tricyclic antidepressant were not significant. PMID- 8468435 TI - Moclobemide versus imipramine in depressed out-patients: a double-blind multi centre study. AB - One hundred and twenty seven patients with major depressive episode were included in a double-blind, four-week, prospective, randomized, multi-centre parallel group trial comparing moclobemide and imipramine. The dose of moclobemide was 150 525 mg/day and that of imipramine 50-175 mg/day; the mean daily doses during the last week of treatment were 307 mg and 100 mg of moclobemide and imipramine, respectively. The decrease of the total scores of the Hamilton Depression Scale (HDRS) as well as the Overall Assessment of Efficacy by the Investigators showed significant amelioration of depression in both treatment groups (p < 0.001). No significant differences were found between the moclobemide and imipramine groups with regard to treatment outcome. The onset of the antidepressant activity was faster in the moclobemide group as measured by the Assessment of the Investigators. This difference was not observed when the therapeutic index figures calculated on the basis of the changes in the HDRS scores were scrutinized. Treatment-emergent side effects were somewhat more frequent during imipramine than during moclobemide treatment. Nevertheless, a total of only four patients discontinued the trial prematurely because of poor tolerability. Imipramine-treated patients reported more anticholinergic side effects, whereas tiredness and headache were observed more frequently in the moclobemide-treated patients. Restlessness, nervousness and sleep disturbances were noted with equal incidence in both patient groups. PMID- 8468436 TI - A comparison study of moclobemide and doxepin in major depression with special reference to effects on sexual dysfunction. AB - A double-blind parallel-group comparison study of moclobemide versus doxepin in 237 patients with major depression confirmed that moclobemide was equal in efficacy and better tolerated than doxepin. It was less sedating and caused fewer anticholinergic adverse events as measured by the UKU side-effect rating scale. Unexpectedly, moclobemide therapy more often than doxepin resulted in increased sexual desire. An exploratory analysis of UKU-measured symptoms of impaired sexual function prior to commencement of the study revealed that moclobemide more often than doxepin led to an improvement of reduced libido and impaired erection, ejaculation and orgasm. This finding is compatible with the assumption that there is a greater likelihood that the anticholinergic reuptake inhibitor doxepin has a higher risk of impairing sexual function than the non-anticholinergic RIMA moclobemide. A single case report of moclobemide-induced sexual hyperarousal supports the alternative assumption that moclobemide has a specific sexually stimulative effect in depression. PMID- 8468437 TI - A double-blind comparison of moclobemide and fluoxetine in the treatment of depressive disorders. AB - Moclobemide and fluoxetine were tested in a six-week trial involving 122 patients with major depressive illness. Patients initially received moclobemide, 150 mg three times daily, or fluoxetine 20 mg/day, but during weeks 3, 4, 5 and 6 the doses could be altered, giving a range of 300-600 mg/day for moclobemide or 20-40 mg/day for fluoxetine. No dietary restrictions were imposed on the patients. The trial was completed by 49 patients receiving moclobemide, and 43 patients receiving fluoxetine. The efficacies of these two agents, as determined on the Hamilton Depression Rating Scale and from Clinical Global Assessments, were found not to differ significantly. The frequencies of occurrence of adverse reactions were also similar, but sedation, nausea and vomiting were reported more frequently with fluoxetine, and insomnia was experienced with moclobemide. Tolerance of both drugs was judged to be high. PMID- 8468438 TI - A randomized, double-blind, multi-centre, parallel-group study comparing the tolerability and efficacy of moclobemide and dothiepin hydrochloride in depressed patients in general practice. AB - A randomized, double-blind, multi-centre, parallel-group study compared the tolerability and efficacy of 450 mg of moclobemide and 75-150 mg of dothiepin in the management of depressed patients in general practice. Patients who fulfilled the DSM-III-R criteria for major depressive disorder and who scored 13 or more on the Hamilton Depression Rating Scale were admitted. The trial lasted six weeks. The dose of moclobemide was 150 mg three times daily and that of dothiepin was 75 mg daily for the first two weeks and 150 mg thereafter. Assessments were made at baseline and after one, three and six weeks using the HDRS, the Zung SRS and the CGI. Adverse events and vital signs were monitored at each visit, and laboratory screening tests performed at the beginning and end of the study. Sixty-four general practitioners from four centres recruited 345 patients: 175 received dothiepin and 170 moclobemide; 265 completed six weeks of treatment. Thirty-eight dothiepin-treated patients (22%) and 42 who received moclobemide (25%) dropped out, most commonly because they experienced adverse events. More patients on dothiepin (24) than on moclobemide (16) dropped out for this reason; the incidence of adverse events was 10% higher in the dothiepin-treated group and of "side effects" more than 10% higher, the latter difference being statistically significant. Both treatments resulted in significant improvement; this was greater in the dothiepin-treated group and the difference was statistically significant, although clinically small. PMID- 8468439 TI - An update of recent moclobemide interaction data. AB - The classical monoamine oxidase inhibitors (MAOIs) are believed to have serious risks because of interactions with other drugs and foodstuffs, although not with a sound scientific basis in all cases. However, moclobemide, a selective reversible inhibitor of MAO-A, has a low propensity for producing drug interactions. Interaction studies have been carried out in healthy volunteers in an attempt to answer some relevant practical questions related to therapy with moclobemide. In combination with therapeutic doses of either fluvoxamine or fluoxetine, moclobemide did not provide any indication of a serotoninergic syndrome, so that no wash-out period is needed when switching from a selective serotonin re-uptake inhibitor to moclobemide or vice versa. Since concomitant treatment with moclobemide and selegiline had a supra-additive effect on the sensitivity to intravenously administered tyramine, that combination therapy should only be considered when accompanied by dietary restrictions. Concomitant treatment with moclobemide and levodopa/benserazide, however, was well tolerated. When oral ephedrine was added to steady-state moclobemide treatment, the cardiovascular effects of the former were increased to about the same extent as for oral tyramine, i.e. a potentiation of 2-4. PMID- 8468440 TI - Effect of moclobemide on the psychophysiology of sleep/wake cycles: a neuroelectrophysiological study of depressed patients administered with moclobemide. AB - The effects of moclobemide, 450 mg/day, on sleep were investigated in 12 patients with major depression. The study was carried out over six weeks, divided into three periods: (1) treatment for one week with placebo and measurement to obtain baseline values; (2) treatment with moclobemide for four weeks; and (3) one week withdrawal period. Polygraphic sleep recording, all-night sleep-EEG spectral analysis, and diurnal EEG vigilance mapping were used to determine the effects of this antidepressant. An activating effect was observed, most marked during the early phase of treatment. The most noticeable effects were on REM sleep, affecting polysomnographic and spectral sleep EEG parameters. A REM sleep habituation phenomenon was observed, and a slight REM sleep rebound effect occurred early during withdrawal. The observed neuroelectrophysiological changes appear to be specific for moclobemide and differ from those brought about by other antidepressants. PMID- 8468441 TI - The costs of depression. AB - Depression is one of the commonest conditions seen by general practitioners. Conventional treatments are typically drug based, and usually involve one of the tricyclic preparations. The evaluation of new treatments requires an understanding of the costs and benefits of existing alternatives, to provide a comparative framework for general practitioners and others concerned with the treatment and management of depressed patients. This paper presents estimates of the direct costs associated with the treatment of patients in England and Wales. These amount to some 420 million pounds annually. Pharmaceutical costs represent a relatively small proportion of this total. Substantial indirect costs are generated through lost productivity, and these may exceed 3 billion pounds. PMID- 8468442 TI - Recurrent brief depression, dysthymia and melancholia. Workshop report. PMID- 8468443 TI - Therapy-resistant depression. Workshop report. PMID- 8468444 TI - Syndromal subgroups of depression. Workshop report. PMID- 8468445 TI - Depression in medical illness. Workshop report. PMID- 8468446 TI - Cytochemical evidence for the presence of phospholipids in epithelial tight junction strands. AB - Previous freeze-fracture experiments using either glutaraldehyde-fixed and cryoprotected specimens or unfixed rapid-frozen samples led to the proposal that cylindrical strands of the tight junction (TJ) observed in freeze-fracture preparations are inverted cylindrical micelles made up of membrane lipids and, possibly, membrane proteins. However, no one has yet been able to directly label the structural fibrils of the TJ. To test the hypothesis that TJ strands observed on freeze-fracture preparations are composed at least partially of lipids, we have combined the phospholipase A2-gold and the fracture-label techniques for localization of phospholipids. Phospholipase A2, purified from bee venom, was adsorbed on gold particles and used for specific labeling of its substrate. Phospholipase A2-colloidal gold (PLA2-CG) complex was applied to freeze-fractured preparations of rat exocrine pancreatic cells and testicular Sertoli cells, both of which are known to have extensive TJ complexes on their plasma membranes. Fracture-label replicas of exocrine pancreatic cells revealed specific association of gold particles with TJ fibrils on the protoplasmic fracture-face of the plasma membrane. The majority of these gold particles were observed either directly on the top of the TJ fibrils or adjacent to these cylindrical structures. A high density of PLA2-CG labeling was also observed over the complementary exoplasmic fracture-face of the TJ complex. This intimate association of PLA2-CG labeling with the TJ is particularly evident in the Sertoli cell plasma membrane, where rows of gold particles were observed to be superimposed on parallel arrays of cylindrical strands of the TJ complex. The present findings provide direct cytochemical evidence to support the hypothesis that cylindrical TJ strands observed in freeze-fracture preparations contain phospholipids. PMID- 8468447 TI - A histochemical procedure for light microscopic demonstration of xanthine oxidase activity in unfixed cryostat sections using cerium ions and a semipermeable membrane technique. AB - Xanthine oxidoreductase exists in two functionally distinct forms. Under normal conditions, the larger part of the enzyme occurs as an NAD(+)-dependent dehydrogenase form which produces NADH and urate. The dehydrogenase can be transformed under various (patho)physiological conditions to an oxygen-dependent oxidase form which produces oxygen radicals and/or hydrogen peroxide and urate. Tetrazolium salts are used to demonstrate the total activity of both the dehydrogenase and the oxidase form of the enzyme. We have developed a procedure to detect the oxidase form only in unfixed cryostat sections with the use of cerium on the basis of the semipermeable membrane technique. The incubation medium contained hypoxanthine as substrate, cerium ions, and sodium azide to inhibit catalase and peroxidase activity. In a second-step reaction, diaminobenzidine was polymerized in the presence of cobalt ions by decomposition of cerium perhydroxide. Large amounts of final reaction product were found in milk droplets in the acini of lactating bovine mammary gland, whereas milk secreting epithelial cells contained hardly any final reaction product. In rat duodenum, enzyme activity was found in the cytoplasm of enterocytes and goblet cells but not in the mucus. Control reactions performed in the absence of substrate or in the presence of substrate and allopurinol, a specific inhibitor of xanthine oxidase, were completely negative in both tissues, with the exception of polymorphonuclear leukocytes in the lamina propria of duodenum. The positive nonspecific reaction in these cells was caused by myeloperoxidase activity. We conclude that the present method is specific for the detection of xanthine oxidase activity. Moreover, conversion of the dehydrogenase form into the oxidase form can be prevented by omission of chemical fixation of the tissue in the present procedure. PMID- 8468448 TI - Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. AB - We investigated the immunohistochemical localization of androgen receptor (AR) using a polyclonal antibody for 55 KD recombinant human AR in human tissues fixed with 4% paraformaldehyde solution and embedded in paraffin. Immunoreactive AR was restricted to the nuclei of various tissues. Among the well-known androgen target organs, secretory cells and basal cells of the prostate, spermatogonia, spermatocytes, Sertoli cells and Leydig cells of the testis, epithelial cells of the rete testis, fibroblasts in the whole organ, squamous cells, sweat gland and hair follicle cells of the skin, and hepatocytes of the liver were positive for AR. In addition, smooth muscle cells of the prostate, uterus, urinary bladder, gastrointestinal tract, arteries, and arterioles were strongly immunoreactive for AR. Cardiac muscle and striated muscle of psoas were positive for AR. Acinar cells, ductal cells, and myoepithelial cells of the breast, endocervical and endometrial cells of the uterus, cyto- and syncytiotrophoblast of the chorionic villi, and tubules of the kidney were also positive for AR. Most FSH, LH, and some GH endocrine cells in the anterior and posterior lobes of the pituitary gland, follicular cells of the thyroid gland, and adrenocortical cells were positive for AR. Cells immunoreactive for AR were ubiquitously distributed throughout the entire body. The present study demonstrated the diversity of androgen effects on many target tissues. PMID- 8468449 TI - Rapid expression of collagen type X gene of non-hypertrophic chondrocytes in the grafted chick periosteum demonstrated by in situ hybridization. AB - We investigated the spatiotemporal localization of collagen Type I, II, and X mRNAs in the subcutaneously grafted chick periosteum by in situ hybridization. Five days after transplantation, we noted three types of histological findings in the grated tissue. (a) Developing trabecular bone exhibited proliferation of spindle-shaped fibroblastic cells and polygonal osteoblasts with moderate signals for collagen Type I mRNA. (b) Developing cartilage contained ovoid chondrocytes with a moderate level of both collagen Type I and II mRNAs. Differentiating chondrocytes with increased collagen Type X mRNA developed during the course of endochondral ossification. (c) An atypical mass of cartilage weakly stained with alcian blue was composed of a large number of non-hypertrophic chondrocytes exhibiting high signals for collagen Type X mRNA. At Day 9, we observed the typical histological features of both membranous and endochondral ossification. However, sparsely distributed chondrocytes with high signals for collagen Type X mRNA were also demonstrated in osteoid and/or woven bone. The phenotype of chondrocytes showing rapid expression of collagen Type X gene derived from grafted periosteum seems to participate in the important role of endochondral bone formation in the early stage of fracture repair. PMID- 8468450 TI - Measurement of metabolic events in the avian epiphyseal growth cartilage using a bioluminescence technique. AB - We developed a technique to map the distribution of selected metabolites in the growth cartilage in situ using luciferase-NAD(P)H:FMN oxidoreductase. Chick tibial epiphyses were freeze-trapped, sectioned, and freeze-dried. For evaluating lactate, luciferase was suspended in a buffer containing polyvinylalcohol, gelatin, NAD, FMN, and lactic dehydrogenase (LDH). The buffer was frozen into a layer 800 microns thick and placed in contact with the tissue section. The temperature of the frozen reagent mixture was then allowed to increase; the emitted light was focused through a photographic lens and collected on film. We found that lactate was synthesized by cells in all regions of the growth plate. The highest concentration of the metabolite was observed in the calcified hypertrophic region. Substantial levels of lactate were also present in articular cartilage. By modifying the composition of the buffer solution, we were able to map the distribution of glucose and glucose-6-phosphate and the activity of LDH. Maximal levels of each of the three components were present in hypertrophic cartilage. Chemical analysis of the tissue section confirmed the luminographic studies and provided further evidence that there was reliance on glycolytic metabolism in terminally differentiated chondrocytes. Use of enzyme couples similar to those described above should permit the technique to be used to study most, if not all, of the major metabolic components of cartilage. PMID- 8468451 TI - Detection of nerve growth factor mRNA in rodent salivary glands with digoxigenin- and 33P-labeled oligonucleotides: effects of castration and sympathectomy. AB - Nerve growth factor (NGF) is a protein highly expressed in the male mouse submandibular gland. We have applied a non-radioactive in situ hybridization method using digoxigenin-labeled NGF oligonucleotides, and have found the highest amounts of NGF mRNA in the secretory striated ducts of the male mouse submandibular gland. Scattered strongly positive cells were found in male mouse sublingual glands. Weakly labeled cells were seen in female mouse and in male rat submandibular gland striated duct cells. Using 33P as an alternative to 32P and 35S, we demonstrated a 1.3 KB NGF mRNA in salivary glands of male mice by Northern blot hybridization. Using 33P we detected NGF mRNA in male mouse submandibular glands by in situ hybridization but with a signal that, compared with the non-radioactive method, had a very low resolution. Castration of male mice almost abolished both the 1.3 KB NGF mRNA seen with Northern blots and the NGF mRNA labeling in submandibular glands 4 weeks after the operation, whereas levels were increased 6 hr and 2 days after sympathectomy. We conclude that hybridization with digoxigenin-labeled NGF oligonucleotides is a good tool to study the expression and regulation of NGF mRNA in male mouse submandibular glands. PMID- 8468452 TI - Antibodies raised against a peptide corresponding to a Gs alpha domain reveal a vimentin-associated protein. AB - In an attempt to localize the guanine nucleotide binding protein Gs alpha by immunocytochemistry, we synthetized peptides corresponding to several stretches of residues deduced from the published cDNA sequence of Gs alpha and raised antibodies against them. Among the peptides, one corresponding to residues 367 381 elicited antibodies that immunocytochemically detected, at the optical level, what appeared to be vimentin in several cells and tissues. Studies at the ultrastructural level confirmed this observation and also showed weak staining of some areas of plasma membranes of glial and nerve cells. Analysis by Western blots of rat brain subcellular fractions indicated that: (a) the protein stained by the anti-peptide antibodies was associated with the cytoskeleton; and (b) it was not vimentin but a protein of higher molecular weight, 65 KD. We accordingly suggest that the Gs alpha-derived peptide elicited two types of antibodies, one recognizing Gs alpha in fixed tissues, the other recognizing an epitope located in a vimentin-associated protein. This study emphasizes the caution that is needed when conclusions are drawn on the basis of immunocytochemical studies using antipeptide antibodies. PMID- 8468453 TI - A comparison of the detection sensitivity of lymphocyte membrane antigens using fluorescein and phosphor immunoconjugates. AB - In this study we compared the sensitivity of immunocytochemical procedures, using conventional and time-resolved fluorescent dyes, in a model system consisting of paraformaldehyde-fixed human lymphocytes. The lymphocytes were stained for the presence of the CD4 epitope by indirect immunofluorescence using FITC as label or by using time-resolved luminescent immunophosphors. These immunophosphors were primarily developed for use under time-resolved fluorescence conditions, but they are also very well suited for use in conventional fluorescence microscopes. The differently labeled cells were first examined visually with a conventional fluorescence microscope in a double-blind study. The fluorescence was also measured with a CCD camera mounted on a specially constructed time-resolved fluorescence microscope which allows the suppression of the fast decaying fluorescence, thereby permitting visualization of the specific, slowing decaying luminescence of the phosphor label. With this microscope FITC and immunophosphor labeled lymphocytes were compared under normal conditions (i.e., continuous excitation) and under conditions of time-resolved registration. Conventional fluorescence microscopy revealed a better sensitivity in favor of the phosphor conjugates. This difference became more prominent when the preparations were quantitatively assessed with the CCD-time-resolved microscope. Time-resolved microscopy permitted a suppression of fast decaying fluorescence better than 1 to 10(6). PMID- 8468454 TI - Quantitative immunohistochemical evaluation by image analysis of metallothionein in copper-loaded rat kidney. AB - Kidneys of copper-loaded rats were investigated immunohistochemically with a directly peroxidase-conjugated monoclonal antibody against metallothionein (MT). By means of an image analyzing system the area and the staining intensity of MT immunoreactivity in the proximal convoluted tubule (PCT) cells were determined. In the present study we compared the data obtained by image analysis with analytically determined tissue copper and MT concentrations of rats fed a high copper diet (1 g/kg) for 16 weeks and sacrificed sequentially during this period. Our results provide evidence that the area of MT immunoreactivity correlates significantly with tissue copper and MT concentrations. Both the copper and MT concentrations in kidney rose to a maximum at 8 weeks and remained constant thereafter. The observed rise in the staining intensity of MT in PCT cells to a maximum at 6 weeks, which subsequently declined, suggests a continuing redistribution of copper and MT in the kidneys even after a maximum of concentration copper and MT is reached in the tissue. PMID- 8468455 TI - The histochemical profiles of fast fiber types IIB, IID, and IIA in skeletal muscles of mouse, rat, and rabbit. AB - This study characterized histochemically three fast fiber types (IIB, IID, IIA) in skeletal muscles of mouse, rat, and rabbit, with special reference to fiber types IIB and IID. The results are complemented by biochemical analyses of myosin heavy chain composition in these muscles. Fiber type delineation is based on various methods for mATPase staining with pre-incubations and assays under different conditions. In rat and mouse, IIB and IID fibers can be best distinguished according to their different mATPase stabilities towards formaldehyde and alkaline pH. In rabbit, the method of Matoba and Gollnick using acid pre-incubation provided best and most reproducible results. In addition to their different mATPase stabilities, the three fast fiber types differ with regard to their oxidative capacities and cross-sectional fiber areas in the three species. In general, Type IIB fibers are the largest and least oxidative, Type IIA fibers the smallest and most oxidative, and Type IID fibers intermediate. In rabbit, Type IID fibers are the predominant fast fiber population in extensor digitorum longus, psoas, and tibialis anterior muscles. As judged from histochemistry, these muscles of rabbit do not contain pure Type IIB fibers. This is in accordance with biochemical results that show the HCIId to form the majority of the myosin heavy chain complement expressed in these muscles. On the other hand, IIB fibers are numerous in rabbit adductor magnus, gastrocnemius, and vastus lateralis muscles. Similarly, appreciable amounts of myosin heavy chain HCIIb are found in the three latter muscles of rabbit. PMID- 8468456 TI - Monitoring of two allergens, Bet v I and profilin, in dry and rehydrated birch pollen by immunogold electron microscopy and immunoblotting. AB - Dry and rehydrated birch pollen grains were anhydrously fixed and double immunogold-labeled for the presence of two allergens, Bet v I major allergen (17 KD) and profilin (14 KD). In dry pollen grains, both allergens are found exclusively inside the cytoplasm. In pollen grains rehydrated for 1 min, the cytoplasm is partially devoid of the two allergens, whereas the pollen wall and the germination aperture are specifically labeled. Pollen grains rehydrated for 5 min are largely free of the two allergens. In immunoblot experiments, both allergens could be detected in the aqueous supernatants of rehydrated pollen samples within 5 min. The results obtained by both methods show the high solubility of both proteins. This makes them readily available to the immune system and characterizes them as potent allergens. Moreover, the solubilization of profilin might indicate a dissociation of the profilin-actin complex at the very first stage of pollen germination, which could favor formation of the cytoskeleton and pollen tube growth. PMID- 8468457 TI - Location of a membrane-bound carbonic anhydrase isoenzyme (CA IV) in the human male reproductive tract. AB - We studied the location of a membrane-bound carbonic anhydrase (CA IV) in the human male reproductive tract using a specific antiserum to human CA IV in conjunction with immunoblotting, immunoperoxidase, and immunofluorescence techniques. The microvilli and apical plasma membrane of the epithelial cells and the subepithelial smooth muscle layer of the epididymis, ductus deferens, and ampulla of the ductus deferens showed specific staining for CA IV. The epithelial cells of the prostate and seminal vesicle failed to stain for CA IV, however, whereas the subepithelial smooth muscle layer showed positive staining. No specific staining for CA II was seen in the epithelium of the epididymal duct or the proximal ductus deferens. The presence of CA IV in the epididymis was confirmed by immunoblotting, which revealed 35 KD and 33 KD polypeptides. The results show that the microvilli and the apical plasma membrane of the lining epithelium of the epididymal duct, ductus deferens, and ampulla of the ductus deferens contain the membrane-bound carbonic anhydrase isoenzyme IV. The presence of the enzyme in the epithelium of the epididymis and ductus deferens is probably linked to the acidification of the epididymal fluid that prevents premature sperm activation. Its physiological role in the smooth muscle cells remains to be elucidated. PMID- 8468458 TI - Immunohistochemical detection of human brown adipose tissue uncoupling protein in an autopsy series. AB - We used an immunohistochemical method for the inner mitochondrial membrane uncoupling protein (UCP) to examine whether human brown adipose tissue UCP could be detected by an anti-rat UCP antibody. Samples of human brown adipose tissue were obtained at medicolegal autopsies. Fat tissue was excised from around the common carotid arteries and in the subscapular region and from around the thoracic aorta. The subjects were either known alcohol consumers, in which thermogenically active brown adipose tissue (BAT) is often found, or victims of sudden infant death syndrome (SID). UCP was detected in all the cases examined, even when the post-mortem time from death to autopsy reached several days, but the intensity of the immunostaining was variable. Intense staining was observed in three cases with a post-mortem time under 24 hr, but in the SID cases a strong positive staining was seen even with a post-mortem delay of 4 days. These results show that an anti-rat UCP antibody can be used for immunohistochemical detection of UCP in human brown adipose tissue and that it provides a useful method for distinguishing between white and brown fat in paraffin-embedded samples. It can be used to detect UCP in the BAT of obese and diabetic individuals and probably also in the histopathological diagnosis of brown adipose tissue lipoma, known as hibernoma. PMID- 8468459 TI - A simple and reliable method for correlative light and electron microscopic studies. AB - We describe in detail a simple method for flat-embedding that can be subsequently used in correlative light and electron microscopic studies. The method can be applied to any material suitable for electron microscopy and is especially useful for study of the synaptology and ultrastructural characteristics of immunocytochemically or morphologically identified neurons or their processes. We present here an example to show how accurately one can delineate the fine details of a complex axonal arborization impregnated with the Golgi method in the mouse cerebral cortex. Golgi-impregnated sections to be studied at the electron microscopic level are osmicated, dehydrated, infiltrated with Araldite resin, flat-embedded, and identified cells or processes photographed. Serial semi-thin sections (1-2 microns thick) are then cut with an ultramicrotome, examined with the light microscope, and the elements rephotographed. Selected semi-thin sections are then resectioned on the ultramicrotome at 60-70 nm and examined electron microscopically. This method allows the systematic and accurate localization of stained cells and processes throughout the successive steps of the procedure. PMID- 8468460 TI - Effect of transforming growth factor-beta on early and late activation events in human T cells. AB - Transforming growth factors-beta (TGF-beta) modulate immune responses by inhibiting the proliferation of normal T lymphocytes. To examine the mechanism(s) of this inhibition, we studied the effect of TGF-beta 1 on selected events associated with the initiation and progression of the T lymphocyte cell cycle. Human peripheral blood T cells were stimulated with anti-CD3 mAb, PHA, PMA, or ionomycin, alone or in combination. TGF-beta 1 (0.5 to 10 ng/ml) partially inhibited the tyrosine phosphorylation of a 100-kDa protein, but not the calcium influx when cells were stimulated via TCR. Nuclear transcription of early activation genes (c-fos, c-jun, and c-myc) as determined by nuclear run-off assays, and steady state mRNA levels and/or protein products of intermediate activation genes (IL-2, IL-2R alpha, IL-2R beta, and transferrin receptor) were not affected by TGF-beta 1. Total cellular RNA synthesis and cell size after T cell stimulation were also not affected by TGF-beta 1. However, TGF-beta 1 inhibited the IL-2-dependent proliferation of Con A lymphoblasts by -50%. This inhibition was associated with the down-regulation of IL-2-mediated tyrosine phosphorylation of proteins of 120, 100, 85, 75, and 50 kDa. TGF-beta 1 also inhibited the IL-2-dependent phosphorylation of the retinoblastoma susceptibility gene product, which plays an important role in cell cycle progression. These results suggest that TGF-beta 1 inhibits T cell proliferation by down-regulating predominantly IL-2-mediated proliferative signals. PMID- 8468461 TI - Separation of T helper 1 clone cytolysis from proliferation and lymphokine production using analog peptides. AB - In this report, we investigate the activation of Th1 clones using altered TCR ligand. By changing the immunogenic peptide, cytolytic function can be separated from proliferative and lymphokine responses. These three responses were examined and dissected in two Th1 clones using analogs of the murine hemoglobin [Hb(64 76)] peptide. This analysis was focused on amino acids in the immunogenic peptide that were possible T cell contact residues. Typically, several amino acids were identified as critical contact residues for a Th1 proliferative response. An examination of lymphokine production (IFN-gamma or IL-3) revealed the same pattern of response to the analog peptides indicating that the proliferative and lymphokine responses were directly related. However, for cytolysis, fewer amino acid residues were identified as critical contact residues for effector function. Thus, some altered peptide ligands allowed the disassociation of the cytolytic function from the proliferative and lymphokine responses in Th1 clones. To extend these findings, the activation of T cell hybridomas created from the Th1 clones were similarly examined using the altered TCR ligands. The lymphokine response (IL-2) of the T cell hybridomas identified the same critical amino acids as did the cytolytic response of the Th1 clones. Thus, analog peptides partially activated the Th1 clones such that cytolysis occurred independent from proliferative and lymphokine responses. PMID- 8468462 TI - Costimulation of peripheral blood T cell activation by human endothelial cells. Enhanced IL-2 transcription correlates with increased c-fos synthesis and increased Fos content of AP-1. AB - Endothelial cells (EC) act as APC for resting PBL in vitro, and may have important roles in vivo in the pathogenesis of allograft rejection and delayed hypersensitivity. We previously reported that human umbilical vein EC provide costimulatory signals to PHA-stimulated PBL via CD2:lymphocyte function associated Ag-3 and an unidentified ligand pair, resulting in a three- to eight fold enhancement of IL-2 production. The physiologic relevance of this increase was demonstrated by the proliferative advantage provided by EC to PBL suboptimally stimulated with mAb OKT3. We now report that EC costimulation causes increased levels of IL-2 mRNA as a result of increased IL-2 transcription in PBL. We therefore examined the effects of EC on T cell nuclear factors known to regulate IL-2 transcription, including c-jun and c-fos-two components of the transcription factor AP-1, NFAT, and others. PBL constitutively express c-jun transcripts, and the level of c-jun mRNA is not altered by PHA activation in the absence or presence of EC. In contrast, c-fos mRNA is absent from resting T cells and is induced on PHA activation. EC alone do not induce c-fos mRNA but augment the level of c-fos mRNA in PHA-activated T cells by 3- to 10-fold. This effect is largely independent of the CD2:lymphocyte function-associated Ag-3 pathway. Gel shift analysis reveals the constitutive presence of nuclear factors in resting PBL that bind to the proximal AP-1 site of the IL-2 promoter and that contain immunoreactive c-Jun but not c-Fos protein. In contrast, AP-1 from PHA-activated cells contains c-Jun and low levels of c-Fos. Strikingly, costimulation with EC results in a dramatic increase (up to 15-fold) in the c-Fos content of AP-1. Levels of other nuclear factors involved in IL-2 regulation were not altered by EC, although NFAT-DNA complexes migrated at a slightly different mobility. In summary, our data suggest that changes in the composition of transcription factor AP-1 is a key molecular mechanism for increasing IL-2 transcription and may underlie the phenomenon of costimulation by EC. PMID- 8468463 TI - Limited usage of T cell receptor V beta genes by allopeptide-specific T cells. AB - T cell reactivity to alloantigens results from direct and indirect recognition of allogeneic MHC molecules and/or peptides. Although direct recognition is not self MHC restricted, indirect recognition, the result of alloantigen processing and presentation by host APC, is restricted by the self (responder) MHC molecule to which the allopeptide has bound. We have studied the MHC restriction and TCR usage in T cell alloreactivity to a synthetic peptide corresponding to amino acid residues 21-42 of the DR beta 1*0101 molecule. T cell lines were developed by in vitro immunization of T cells from three responders carrying the DR beta 1*1101 allele with this peptide. In all three responders, reactivity to peptide 21-42 was restricted by the DR11 molecule. A limited usage of V beta genes was found in these T cell lines, all of which shared the expression of V beta 13.2. Because indirect recognition of allopeptide may play an important role in chronic, antibody-mediated allograft rejection, study of the TCR gene usage may contribute to the development of specific immunosuppression therapy. PMID- 8468464 TI - Invariant chain retains MHC class II molecules in the endocytic pathway. AB - During exocytosis of MHC class II, the class II alpha beta heterodimer associates with a third polypeptide termed invariant chain (Ii). Class II and Ii are coordinately processed and transported until proteolytic cleavage of Ii in an acidic compartment immediately before class II surface expression. Although the lysosomotropic agent chloroquine (CQ) prevents dissociation of class II/Ii within the cell, the ultimate fate of these complexes has not been determined. We considered two alternative possibilities. If Ii encodes an intracellular retention signal, then persistent association of Ii with class II could lead to intracellular accumulation of class II/Ii complexes. Alternatively, if Ii does not block further transport of class II, then CQ treatment should result in aberrant expression of class II/Ii complexes at the cell surface. Ltk- and EL4 cells transfected with I-A(d) alone or I-A(d) plus Ii were treated with CQ and examined for changes in surface class II and Ii expression. Anti-Ii mAb surface staining did not increase with prolonged CQ treatment, but a dramatic decrease in surface class II staining was observed. This decrease in class II was observed both with genomic Ii and p31 cDNA transfectants and was rapidly reversed upon drug removal. Accumulation of Ii and class II within treated cells was directly observed by intracellular staining. Similar effects on MHC surface expression were observed with the lysosomotropic agents primaquine and NH4Cl and the cysteine protease inhibitor leupeptin. Ii-negative cells treated in parallel displayed no effect of the lysosomotropic agents or leupeptin on class II surface staining. These results indicate that dissociation of Ii from newly synthesized class II is required for transport of the alpha beta dimer to the cell surface, and suggest that Ii serves to retain class II molecules in a post-Golgi endocytic compartment. PMID- 8468465 TI - Modulation of the intracellular Ca2+ and inositol trisphosphate concentrations in murine T lymphocytes by the glycosylphosphatidylinositol-anchored protein sgp-60. AB - Stimulation of T lymphocytes via the TCR/CD3 complex initiates a series of intracellular biochemical events. Among the earliest cellular responses are the stimulation of the turnover of phosphatidylinositol and an increase in the intracellular Ca2+ concentration. The significance of these second messengers for distal cellular responses such as lymphokine production or cell proliferation is not understood. We have previously shown that hamster mAb to the murine glycosylphosphatidylinositol-anchored protein sgp-60 can inhibit IL-2 production, IL-2R expression, and cell proliferation, events normally observed after stimulation of T cells with an antibody to the TCR/CD3 complex or with the lectin Con A. We now show that the anti-sgp-60 mAb inhibits the activation-induced increase in intracellular Ca2+ concentration. Additional analysis demonstrates that the mAb interferes with the release of Ca2+ from intracellular stores and with the generation of inositol 1,4,5-trisphosphate. Our findings suggest a role for this glycosylphosphatidylinositol-anchored protein in the generation of second messengers in signal transduction through the TCR/CD3 complex in murine T lymphocytes. PMID- 8468466 TI - IL-10 inhibits T cell-independent but not T cell-dependent responses in vitro. AB - Lymphokines play a key role in T cell-independent (TI) Ag-induced responses. We recently showed that IL-10 potently inhibits Ig production stimulated by TI-2 Ag + IL-5. In view of our recent findings that the B cell activator can determine the effect lymphokines will have on Ig production and on isotype selection, we analyzed the effect of IL-10 on Ig production induced by other TI antigens and T cell-dependent Ag. These data demonstrate that IL-10 inhibited IL-5-induced Ig production stimulated by TI-1 and by TI-2 Ag, but had no effect on an in vitro T cell-dependent Ag-specific anti-SRBC-induced response or on a T cell-induced polyclonal response mediated by anti-CD3-activated T cell clones. IL-10 inhibited IgM, IgG1, IgG2a, and IgG3 secretion by B cells costimulated by LPS or anti-delta dextran. IL-10 did not interfere with induction of class II MHC Ag expression or cell enlargement that was stimulated by LPS or anti-delta-dextran and had no detrimental effect on cell viability. IL-4 reversed the IL-10-mediated inhibition of IgG1 and IgM secretion stimulated by anti-delta-dextran or LPS-activated cells in the presence of IL-5. A 72 h, but not 24 h, exposure to IL-4 at initiation of culture with anti-delta-dextran + IL-5 + IL-10 was necessary to reverse the IL-10 mediated inhibition of IgM secretion. Our data suggest that IL-10 can selectively inhibit TI Ag-induced responses when other T cell-derived stimulatory lymphokines are not present and further emphasize the specific role of the B cell activator in influencing the responsiveness of B cells to lymphokines. PMID- 8468467 TI - Staphylococcus aureus Wood 46 strain activates human B cells without affecting DNA synthesis or tyrosine phosphorylation. AB - Induction of Ig secretion in human tonsilar B cell by protein A-deficient Staphylococcus aureus WOOD 46 strain (SAW) was examined. SAW induced as much Ig secretion as protein A-rich S. aureus Cowan I strain (SAC) when IL-2 was present in the culture. Activated and resting B cells are separated by Percoll gradient to determine whether SAW stimulates either resting or activated B cells. In resting B cells, SAW plus IL-2 induced IgM secretion significantly, but neither IL-2 nor SAW alone induced IgM secretion. In activated B cells, however, IL-2 induced IgM secretion by itself and SAW plus IL-2 did not induce additional IgM secretion. These results suggest that SAW activates small resting B cells rather than preactivated B cells. Subsequently, mechanisms of B cell activation by SAW and SAC were compared. SAW did not induce [3H]-TdR incorporation through day 1 to 5, and the number of viable cells was not increased by SAW stimulation. Moreover, SAW did not induce significant tyrosine phosphorylation at any concentration tested, when tyrosine phosphorylation of B cells was examined. However, SAC induced both [3H]-TdR incorporation and tyrosine phosphorylation of B cell efficiently. In further experiments, induction of IL-2R and IgM mRNA expressions were examined. SAW by itself induced IL-2R and IgM mRNA expressions without affecting expression of membrane-type IgM mRNA. These results show that SAW activates human B cells in quite a different manner from SAC by up-regulating the expression of secretory type IgM mRNA without affecting cell proliferation nor tyrosine phosphorylation, proposing a distinct B cell activation model from SAC. PMID- 8468468 TI - Selective inhibition of T cell activation by an inhibitor of S-adenosyl-L homocysteine hydrolase. AB - Defects in the enzymes involved in the pathway of S-adenosylmethionine (AdoMet) metabolism, or inhibition of those enzymes, results in profound immunodeficiency. We have examined MDL 28,842, a novel irreversible inhibitor of S-adenosyl-L homocysteine hydrolase (AdoHcyase), an enzyme involved in AdoMet metabolism, to determine its effect on the immune system and to investigate its potential as an immunosuppressive agent. The stimulation of human mononuclear cell proliferation in vitro with Con A, a T cell mitogen, and PWM, a T-dependent B cell mitogen, were inhibited by MDL 28,842. The 50% inhibitory concentration for both were 0.33 microM. In murine spleen cells, MDL 28,842 was a potent, nontoxic, inhibitor of Con A-stimulated T cell proliferation (IC50 = 0.19 microM) but did not affect LPS induced B cell proliferation. This selective suppression was also observed when enriched murine T and B cells were stimulated with mitogens, although S-adenosyl L-homocysteine (AdoHcy), the substrate of AdoHcyase, was similarly elevated in both populations. In addition to proliferation in response to a number of stimuli, IL-2 production and the expression of IL-2R by mitogen-stimulated T cells were inhibited by MDL 28,842. These results suggest a direct effect of MDL 28,842 on T cells. In vivo, the antibody response to a T cell-dependent Ag, OVA, was inhibited by MDL 28,842. The response of splenic T cells from these animals to OVA in vitro were similarly depressed compared with controls. The results demonstrate that MDL 28,842 is a potent nontoxic immunosuppressive agent, which has selectivity for T cells and therefore may be useful in the treatment of T cell-mediated disorders, such as autoimmune disease and tissue transplantation. PMID- 8468469 TI - Inhibition of murine T cell activation by cholera toxin B subunit is not mediated through the phosphatidylinositol second messenger system. AB - Although cholera toxin B subunit is a potent mucosal immunogen in vivo, its predominant effect in vitro is inhibition of T cell and B cell activation. We reported earlier that this inhibition was not mediated through activation of adenylate cyclase and increases in intracellular cAMP. There is increasing evidence that T cell activation is initiated through the phosphatidyl inositol second messenger system in which phosphatidyl inositol bisphosphate is hydrolyzed by phospholipase C, producing inositol trisphosphate (IP3) and diacylglycerol. IP3 increases cytosolic calcium and diacylglycerol binds, translocates, and activates protein kinase C (PKC). These signals lead to a complex series of events eventuating in activation of a number of genes important in cell proliferation. In this study, we asked whether the mechanism of T cell inhibition by B subunit of cholera toxin (CT-B) was due to interference with the phosphatidyl inositol second messenger system. We found that substitution of ionomycin and PMA for IP3 and diacylglycerol, respectively, in culture induced T cell proliferation but only if both were present simultaneously. Such proliferation was inhibited by CT-B even if added hours after the start of culture. An assay for cytosolic PKC activity demonstrated that PMA translocation of PKC from cytosol to membrane was not inhibited by CT-B, indicating that CT-B does not inhibit activation of PKC. There was no inhibition of Con A-stimulated T cell phosphoinositol turnover. Moreover, Con A added to Fura-2 AM-loaded cells caused a rapid rise in cytosolic calcium, which CT-B preincubation did not alter. These results indicate that CT-B did not inhibit IP3 generation or action. We next looked at expression of genes involved in T cell proliferation. CT-B inhibited the production of IL-2 by mitogen-activated T cells; Northern analysis showed that this inhibition was associated with decreased levels of IL-2 mRNA. Expression of IL-2R and of transferrin receptors was only modestly reduced. Despite the presence of IL-2R on the T cells exposed to CT-B, the addition of exogenous IL-2 to the cultures did not reverse the CT-B-induced T cell inhibition. We conclude that the T cell inhibition by CT-B is not mediated by interference with the activation of the phosphatidylinositol second messenger system but occurs at a later stage of T cell activation. PMID- 8468470 TI - A protein of the AP-1 family is a component of nuclear factor of activated T cells. AB - Nuclear factor of activated T cells (NF-AT) is a transcriptional activator involved in the induction of IL-2 gene expression. The response element for NF-AT is a sequence localized between -285/-254 in the IL-2 regulatory region. The composition of NF-AT protein is still not fully elucidated. We demonstrate that, in normal human T cells, an AP-1 protein is a component of the NF-AT protein complex. This was evidenced by the ability of the AP-1 site to compete with the NF-AT site for binding to NF-AT and by the capacity of immobilized anti-Jun and anti-Fos antibodies to deplete NF-AT-binding activity from nuclear extracts of activated T cells. There was no detectable binding of in vitro translated Jun/Fos heterodimer (AP-1) to the NF-AT sequence, and the NF-AT sequence was unable to inhibit the binding of Jun/Fos to the AP-1 sequence. The presence of an AP-1 protein in the NF-AT protein complex may regulate NF-AT-binding activity through protein-protein interaction. PMID- 8468471 TI - Genomic composition and allelic polymorphisms influence V beta usage by the Mycoplasma arthritidis superantigen. AB - The Mycoplasma arthritidis superantigen (MAM) is produced by an organism that causes systemic disease in rodents leading to chronic proliferative arthritis. MAM is a typical superantigen that requires presentation to T cells by MHC molecules without processing and T cell recognition of MAM occurs through the V beta chains of the TCR. Several major findings are presented here. First, different MAM-MHC class II isotype complexes may engage different sets of V beta TCR. Thus, activation of V beta 6- and V beta 8.3-bearing T cells is more dependent upon the I-E molecule of the murine H-2 MHC than is activation of cells bearing the V beta 5.1, 8.1, and 8.2 TCR. Secondly, both genomic composition and allelic polymorphisms at the V beta chain segment of the TCR exert profound effects upon the pattern of V beta that are used by MAM. Thus, in V beta b haplotype mice, MAM engages V beta 5.1, 6, and the V beta 8 family of TCR whereas in V beta a (C57BR) and V beta c (RIIIS) haplotype mice that lack various combinations of these V beta, activation of cells bearing V beta 1, 3.1, 7, and 16 can be demonstrated. These differences in V beta usage by MAM appear to be caused by both differences in the avidity of MAM for the various V beta s and to structural allelic polymorphisms in these V beta. Clonal expansion of specific V beta in vivo after injection of MAM is also dependent upon the genomic composition of the mice, because expansion of the V beta 8 TCR seen in V beta b haplotype mice (B10.RIII) whereas marked expansion of V beta 6 is seen in V beta a mice (C57BR). In as much as these TCR have been implicated in a number of experimental autoimmune diseases, MAM may represent an ideal model to evaluate the role of superantigens in the triggering of autoimmune disease. PMID- 8468472 TI - Regulation of MHC class I and beta 2-microglobulin gene expression in human neuronal cells. Factor binding to conserved cis-acting regulatory sequences correlates with expression of the genes. AB - MHC class I molecules are coexpressed with beta 2-microglobulin (beta 2-M) on many somatic cells. However, these proteins are normally not present on cells of the central nervous system (CNS). Cells derived from human neuroblastomas were used as a model for investigating the molecular basis for the paucity of MHC class I and beta 2-M gene expression in neural cells and for the induction of these genes by two cytokines, IFN-gamma, and TNF-alpha. These cytokines independently increased MHC class I and beta 2-M cell surface expression on the neuroblastoma cell lines. IFN-gamma or TNF-alpha also increased MHC class I and beta 2-M steady-state RNA levels and the expression of MHC class I and beta 2-M CAT reporter constructs transiently transfected into the neuroblastoma cell lines, indicating that the cytokines acted by increasing the transcription of these genes. MHC class I and beta 2-M genes share two conserved regulatory elements, an NF kappa B-like site and the IFN consensus sequence, that act as a constitutive enhancer and an IFN-responsive element, respectively. Low MHC class I and beta 2-M gene expression in these cells was accounted for by undetectable to low factor binding activity specific for the above regulatory elements of these genes. TNF-alpha increased factor binding activity specific for the NF kappa B-like elements and IFN-gamma increased factor binding activity specific for the IFN consensus sequence elements of the MHC class I and beta 2-M genes, but not vice versa. Taken together, our results indicated that IFN-gamma and TNF alpha increased MHC class I and beta 2-M gene expression in the neuroblastoma cell lines by inducing factor binding to the regulatory elements present in both genes. PMID- 8468473 TI - Endogenous Ig production in mu transgenic mice. I. Allelic exclusion at the level of expression. AB - Our findings indicate that allelic exclusion is maintained in B cells that successfully rearrange and express and endogenous H chain gene, despite carrying a functionally rearranged H chain transgene (17.2.25 mu a). Cloned hybridomas having a functionally rearranged endogenous H chain gene as well as the transgene produce only endogenous gene products. Some of these hybridoma cultures, upon continuous growth, will secrete transgene as well as endogenous gene products. However, the two H chain polypeptides appear to be made by different cells. In each of three cases of such "double producer" lines examined, further subcloning at this time reveals two types of clones: those that secrete only transgene and those that secrete only endogenous H chains. The clones producing transgene product have lost the functionally rearranged endogenous H chain genes, whereas the clones producing endogenous gene products still contain both transgene and endogenous functionally rearranged H chain genes. These results indicate that hybridomas expressing endogenous Ig have transgene copies that are potentially functional but are reversibly silenced by an unknown mechanism and suggest that inhibition of transgene expression may be mediated by endogenous Ig gene expression. PMID- 8468474 TI - Endogenous Ig production in mu transgenic mice. II. Anti-Ig reactivity and apparent double allotype expression. AB - In 17.2.25 mu transgenic mice (M54, M95), many of the expressed Ig, whether encoded by the transgene or endogenous H chain genes, react with Ig. IgM antibodies encoded by the 17.2.25 mu transgene transfected into J558L myeloma cells are also Ig reactive. In addition, anti-Ig reactivity was manifested by antibodies of the IgM, IgG, and IgA isotypes from the transgenic mice, suggesting that this characteristic reactivity is associated with VH and VL domains of these antibodies. These antibodies bind the (Fab')2 fragment of mouse IgG1 mAb known to be directed against C mu allotypic determinants. This finding could account for the so called "double producer" B cells found in mu transgenic mice and previously identified in serologic assays conducted with two different anti-mu allotypic reagents. In transgenic mice, a high frequency of the antibodies encoded by the transgene or endogenous H chain genes react with polyclonal and monoclonal antiidiotypic antibodies raised against the 17.2.25 Id. The idiotypic and/or antiidiotypic reactivity displayed by antibodies derived from these transgenic mice is similar to that of antibodies expressed by neonatal B cells of normal mice. Thus, our data suggest that transgene expression can play an important role in shaping the endogenous repertoire of antibody specificities. PMID- 8468475 TI - Unexpected effects of the IL-2 receptor alpha subunit on high affinity IL-2 receptor assembly and function detected with a mutant IL-2 analog. AB - Binding of IL-2 to the high affinity IL-2R results in the formation of a stable complex consisting of IL-2 and at least three distinct, noncovalently associated receptor subunits: IL-2R alpha (p55), IL-2R beta (p70-75), and IL-2R gamma (p64). Ligand binding also stimulates the rapid endocytosis of this receptor complex. To gain further insight into the function of the various subunits of the multicomponent high affinity IL-2R complex, we have carried out binding, internalization, and proliferation assays using an IL-2 analog designated F42A that contains a single Phe for Ala amino acid substitution at position 42. This mutation markedly reduces the intrinsic affinity of the resultant IL-2 analog for the low affinity IL-2R alpha subunit although having little or no effect on binding to the IL-2R beta (or IL-2R beta/gamma) intermediate affinity receptor. We have confirmed that F42A does not bind to the IL-2R alpha chain when expressed alone on MT-1 cells or in the presence of the large or small excess of IL-2R beta chains present on either YT-1 cells or forskolin-induced YT-1 cells, respectively. However, although F42A does not interact with the large number of low affinity IL-2R alpha chains present on HUT 102B2 cells, this ligand does bind to the small number of IL-2R beta chains present on these cells with at least 10 fold higher than expected affinity. These findings indicate that excess IL-2R alpha chains may exert positive effects on binding perhaps by changing the conformation of IL-2R beta. In F42A-stimulated internalization assays on forskolin-induced YT-1 cells, the IL-2R alpha chain is consistently endocytosed together with the IL-2R beta subunit indicating that IL-2R alpha is stably associated with the F42A-IL-2R beta complex even though the alpha-subunit contributes little if any affinity to the F42A binding reaction. In proliferation assays on mouse IL-3-dependent pro-B BA/F3 cells stably coexpressing transfected human IL-2R alpha and IL-2R beta subunits (but a mouse IL-2R gamma subunit), F42A proved to be a more effective agonist of growth than wild-type IL-2. These results suggest that the interaction between wild-type IL-2 but not F42A and the IL-2R alpha subunit in this mixed species high affinity receptor complex may induce an unfavorable receptor conformation leading to diminished rather than enhanced growth signal transduction. PMID- 8468476 TI - Transcriptional analysis of inhibition of lipopolysaccharide response by anti IgM. AB - Murine splenic B cells, when stimulated with LPS, show a generalized enhancement of gene transcription. In addition to this general increase, there is a specific increase in microseconds mRNA production and differentiation to high rate IgM secretion. Anti-mu added concomitantly with LPS at the start of culture has been demonstrated to inhibit the LPS-induced increase in microseconds mRNA production without affecting the proliferative capacity of the cells. By "run-on" analysis of nascent transcription, we have shown that the effect of anti-mu is mediated by the abrogation of the up-regulation of transcription of the mu-gene induced by LPS. Furthermore, by assessing the site of transcription termination, it is possible to infer that alterations in 3'-end processing induced by LPS are also inhibited. We have also found that CAT3 gene activity driven by a number of promoter/enhancers with diverse regulatory motifs are inhibited by anti-mu. These results suggest that the effect of anti-mu cannot be restricted to interactions with a single regulatory element. Therefore, cross-linking of surface IgM may affect a number of genes involved in differentiation to Ig secretion. PMID- 8468477 TI - Characterization of the alpha subunit of the IFN-alpha receptor. Evidence of N- and O-linked glycosylation and association with other surface proteins. AB - We studied the association of the alpha subunit of the (IFN-alpha-receptor) to other receptor components in the human H-929 and U-266 myeloma cell lines. Immunoprecipitation performed with the IFNaR3 mAb showed that two proteins with molecular masses of 205 and 145 kDa are co-precipitated with the alpha subunit. These complexes may not bind IFN-alpha as shown by studies using the heterobifunctional cross-linking reagent Denny-Jaffe and by partial cleavage of the homobifunctional cross-linker dithio succinimidyl propionate. These studies also provided evidence that at least two subunits with molecular mass of 130 kDa (alpha subunit) and 110 kDa (including 20 kDa corresponding to IFN-alpha) contribute to the formation of the IFN-alpha-receptor complex. To further characterize the alpha subunit of the IFN-alpha-receptor, immunoprecipitates using the mAb IFNaR3 were sequentially treated with N-glycanase, neuraminidase and O-glycanase. These studies showed that the alpha subunit is heavily glycosylated and has a protein precursor with a molecular mass of 68 kDa. Binding studies provided evidence for high and low affinity binding sites for IFN-alpha 2. Affinity cross-linking experiments under low and high affinity conditions suggest that the high affinity binding site of the IFN-alpha-receptor is formed by a complex containing the alpha subunit, whereas the 110-kDa subunit may bind IFN-alpha 2 under low affinity conditions. PMID- 8468478 TI - Mice treated with a leumedin or antibody to Mac-1 to inhibit leukocyte sequestration survive endotoxin challenge. AB - Endotoxin challenge causes metabolic dysfunction mediated by TNF, and sequestration of leukocytes. NPC 15669, N-carboxy-L-leucine, N-[2,7 dimethylfluoren-9-yl)methyl] ester, inhibits leukocyte recruitment into inflammatory lesions in animals, and inhibits endotoxin-induced neutropenia and lymphopenia in mice. This study was carried out to determine whether the ability of NPC 15669 to inhibit leukocyte sequestration is sufficient to promote survival after endotoxin challenge. To inhibit leukocyte sequestration directly, mice were treated with anti-CD11a (LFA-1) or anti-CD11b (Mac-1) before endotoxin challenge. Anti-CD11b partly inhibited neutropenia and lymphopenia in response to challenge with LPS, but anti--CD11a had little effect on leukopenia. At doses of 100 and 1000 micrograms/kg, anti-CD11b increased survival to endotoxin challenge from 0 to 20 and 40%, respectively, whereas anti-CD11a was without effect. These observations, coupled with the finding that NPC 15669 does not inhibit endotoxin induced TNF release suggest that inhibition of leukocyte sequestration can increase survival after endotoxin challenge, and that NPC 15669 or antibodies to Mac-1 may represent effective therapies for gram-negative sepsis and shock. PMID- 8468479 TI - Effects of cytokines on multiplication of Toxoplasma gondii in microglial cells. AB - Microglia may play a role in host defense against Toxoplasma gondii in the central nervous system. In our study, the antitoxoplasma activity of murine microglia was investigated. T. gondii multiplied readily in cultured microglial cells, and activation of these cells with IFN-gamma plus LPS suppressed (p < 0.01) intracellular growth of this parasite. This antitoxoplasma defense of activated microglia was significantly blocked by neutralizing antibodies against TNF-alpha and transforming growth factor-beta, suggesting that these cytokines play a role in the inhibitory process. Consistent with this hypothesis, activation of microglia with IFN-gamma plus TNF-alpha or transforming growth factor-beta inhibited, in a dose-dependent manner, T. gondii multiplication. Treatment with pentoxifylline or dexamethasone, drugs that suppress production of TNF-alpha, prevented (p < 0.01) the microglia from exerting an anti-T. gondii effect. These findings suggest that the host defense function of microglia against T. gondii is dependent primarily on the activating properties of IFN gamma and TNF-alpha, and that agents that interfere with cytokine-mediated activation may promote the pathogenesis of this infection. PMID- 8468480 TI - Different appearance of gamma delta T cells during salmonellosis between Ityr and Itys mice. AB - Ity gene, which is believed to be a single gene on proximal mouse chromosome 1, determines susceptibility to Salmonella infection. We have recently demonstrated that the gamma delta T cells specific for purified protein derivative appear at the early stage after infection with Salmonella choleraesuis strain 31N-1 (avirulent strain) in mice. In the present study, we compared the appearance of the gamma delta T cells in Ityr and Itys mice after infection with S. choleraesuis in an attempt to elucidate the role of the gamma delta T cells in the in vivo effect of the Ity locus on murine salmonellosis. The numbers of gamma delta T cells in the peritoneal cavity and liver were significantly larger in DBA/2 (Ityr) mice than those in BALB/c (Itys) mice after infection with a sublethal dose of S. choleraesuis. C.D2 Ityr mice, which are BALB/c mice with Ityr allele, also showed a significant increase in the number of the gamma delta T cells at the early stage after infection. Similar results in different appearances of the gamma delta T cells could be obtained between BALB/c and DBA/2 mice after infection with Mycobacterium bovis, bacillus Calmette-Guerin. The peritoneal adherent cells of DBA/2 mice infected with S. choleraesuis, which expressed a large amount of heat shock/stress protein (hsp) homologous to the mycobacterial 65-kDa hsp, induced significantly higher level of expansion of the peritoneal gamma delta T cells in normal mice in vivo and in vitro than did those of BALB/c mice infected with S. choleraesuis, which expressed a lesser amount of the hsp. These results suggest that the Ity locus may be closely related to the expression of hsp by macrophages after infection with Salmonella, which in turn stimulate the gamma delta T cells in the host during an early phase of salmonellosis. PMID- 8468481 TI - A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3. AB - The immune response that is characteristic of parasitic helminth infections includes components associated with immediate-type hypersensitivity: elevated serum IgE, eosinophilia, and intestinal mast cell hyperplasia. In infection with the parasitic nematode, Heligmosomoides polygyrus, IL-4 mediates protective immunity, suggesting the presence of a host-protective Th2 response. In this investigation, we examined early stages of immune responsiveness to H. polygyrus infection to determine whether and at what stage a specific Th2-like pattern first appears. Using a quantitative reverse transcriptase-polymerase chain reaction assay, we analyzed changes in IL-2, IFN-gamma, IL-3, IL-4, IL-5, IL-6, IL-9, and IL-10 gene expression in the spleen, mesenteric lymph node, and Peyer's patch at various time points after infection. Our results demonstrate a highly specific and reproducible pattern of cytokine gene expression that remains localized to the enteric region. By 6 h after infection, IL-5 and IL-9 mRNA were elevated in the Peyer's patch and IL-3 was elevated by 12 to 24 h after infection. IL-4 RNA became elevated by 4 to 6 days after infection, but little change was observed in IFN-gamma, IL-2, or IL-10 mRNA levels. The early increases in IL-3, IL-5, and IL-9 gene expression after infection were probably T cell independent, inasmuch as they were observed in Peyer's patches of congenitally athymic mice and anti-CD4, anti-CD8 mAb-treated conventional mice. However, treatment with these mAb considerably decreased cytokine gene expression 6 days after infection, and 8 days after infection, increased IL-4 gene expression in mesenteric lymph node cells was restricted to the CD4+ population. Thus, H. polygyrus infection induces cytokine gene expression that is restricted to some Th2-associated cytokines, is initiated by a T-independent response, and culminates in a T-dependent response. PMID- 8468483 TI - Expression of the leukocyte common antigen CD45 by endothelium. AB - The CD45 family of Ag expressed by leukocytes play a key role in lymphocyte activation. In this study, we identify both a restricted pattern of expression of CD45 Ag by human endothelial cells and differences in m.w. of endothelial CD45 compared with lymphocyte CD45. Initially, immunoperoxidase staining of endothelial cells in culture revealed the presence of the CD45RO isoform provided the endothelial cells had been stimulated by IL-1 for several days. No other isoform of CD45 was detected by immunoperoxidase staining of endothelium. Leukocyte common antibodies, reputed to detect all isoforms of CD45, did not detect endothelial CD45RO. A polymerase chain reaction method was then used to demonstrate that the message for the CD45RO isoform was constitutively present, with increased levels after IL-1 stimulation. Western blot confirmed the presence of the RO isoform. No other CD45 isoform was detected, either by PCR amplification for message or by Western blot. There were clear differences between lymphocyte and endothelial CD45. The RO isoform expressed by endothelium has an estimated M(r) of 235,000 in contrast to lymphocyte RO that, on our gels, has an estimated M(r) of 190,000. Given the large surface area of endothelium (approximately 1 km2 in the human), the close apposition of lymphocytes and endothelium in immunologic tissues such as lymph nodes, and the pivotal role CD45 plays in activation, expression of CD45RO by endothelium may have important implications in lymphocyte-endothelial interactions. This is most likely to occur in endothelium after a few days of IL-1 stimulation, e.g., at sites of chronic inflammation, or in the draining lymph node of an inflammatory focus. PMID- 8468482 TI - Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. AB - Intestinal intraepithelial lymphocytes (iIEL) are a distinct subpopulation of T lymphocytes diffusely distributed in the epithelium. Because > 95% of these iIEL express the integrin alpha E beta 7, we reasoned that this integrin might mediate the localization of iIEL to the epithelium. We report that cultured iIEL bound to mucosal epithelial cells derived from either breast or intestine. This binding was dependent on the presence of divalent cations, and was blocked by mAb specific for two integrins, alpha E beta 7 and alpha L beta 2. After TGF-beta 1 treatment, cultured iIEL cell lines expressed alpha E beta 7 at levels similar to those found on iIEL in vivo. Under these conditions this integrin appeared to predominate in mediating the adhesion of iIEL to epithelial cells. Although alpha L beta 2 blocked the adhesion of iIEL to both endothelial and epithelial cells, alpha E beta 7 blocked binding only to epithelial cells suggesting that the ligand for alpha E beta 7 is not expressed on IL-1 beta-treated cultured endothelial cells. iIEL did not readily bind to the apical surface of confluent polarized epithelial cell monolayers. However, iIEL did bind to these cells when tight junctions were disrupted, a treatment that allows redistribution of proteins compartmentalized to the basolateral surface. This binding was also blocked by mAb to alpha E beta 7. In addition, in vitro coculture of iIEL with polarized epithelial cells resulted in basolateral localization of the iIEL. Thus, it is likely that expression of the alpha E beta 7 ligand is restricted to the basolateral membrane of polarized epithelial cells. Because alpha E beta 7 appears to be a predominant integrin on freshly isolated iIEL, we hypothesized that alpha E beta 7-mediated adhesion may be particularly important in cell-to cell interactions between T cells and epithelial cells in vivo. PMID- 8468484 TI - Enhancement of antigen-induced bronchoconstriction after intravascular complement activation with cobra venom factor. Reversal by granulocyte depletion. AB - Our previous studies have demonstrated that activation of the C system with cobra venom factor (CVF) in a passively sensitized guinea pig results in an enhanced bronchoconstrictor response to Ag but not to other constrictor agents. Thus, our immediate goal was to determine the mechanism of the CVF-induced enhancement of the Ag-induced bronchoconstriction. Isolated airways from sensitized guinea pigs that had been treated with CVF responded normally to Ag. Because such a system lacks the normal circulating cell populations, we hypothesized that the CVF induced enhancement of the Ag-induced bronchoconstriction was dependent on the presence of circulating white blood cells or platelets. Guinea pigs were depleted of circulating granulocytes, platelets, or both using specific antisera and the effect on the CVF-induced enhancement of the Ag-induced bronchoconstriction was determined. We found that CVF treatment did not result in an enhanced Ag-induced bronchoconstriction in guinea pigs depleted of either granulocytes or both granulocytes and platelets. However, the enhanced response was still apparent in guinea pigs depleted of just platelets. We investigated the effects of CVF itself and found that CVF treatment did not alter the number, or percentages, of different cell populations in the bronchoalveolar lavage, did not alter the protein or albumin content of the lavage fluid or the wet:dry ratio of the lung. In addition, CVF did not cause an increase in airway microvascular permeability as assessed by leakage of Evans blue. However, CVF did substantially increase granulocytes sequestered in the lung as measured by increased myeloperoxidase content. Thus, C activation by CVF results in an increase in neutrophils in the lung and an enhanced Ag-induced bronchoconstriction dependent on the presence of circulating granulocytes. These studies suggest that C activation and/or retention of granulocytes in the lung may be important in determining the severity of an Ag-induced bronchoconstriction. PMID- 8468485 TI - Cytokines and dexamethasone modulation of IL-1 receptors on human neutrophils in vitro. AB - Modulation of IL-1R on human neutrophils was investigated after in vitro treatment of cells with human recombinant (hr) granulocyte (G)-CSF, hrgranulocyte macrophage (GM)-CSF, hrCSF-1, hrIL-1 alpha, hrIL-2, hrIL-3, hrIL-4, hrIL-5, hrIL 6, hrIL-7, transforming growth factor-beta 1, or hrTNF-alpha. At 4 degrees C, 125I-IL-1 binding was competed by IL-1 but not by other cytokines tested. At 37 degrees C, GM-CSF, TNF-alpha, and IL-1 decreased 125I-IL-1 binding in a dose dependent manner. Kinetic studies showed that GM-CSF reduced > 45% IL-1 binding within 15 min but later (8 h) produced a > 2-fold increase. In contrast, TNF decreased > 85% IL-1 binding within 15 min with a recovery of > 80% relative to that of control after 24 h. Scatchard analysis revealed that TNF or GM-CSF down modulation of IL-1 binding was due to a decrease of IL-1R number. Further studies showed that dexamethasone and GM-CSF (or G-CSF) synergistically increased IL-1 binding after 8 h. This synergistic modulation was a cytokine dose- and time dependent process, and was due to an increase in IL-1R numbers rather than a change in binding affinity. In addition, human bone marrow neutrophils, cord blood neutrophils, and several human hematopoietic cell lines (HL-60, U-937, and AML-193) responded to dexamethasone and GM-CSF (or G-CSF) with a superadditive increase in IL-1 binding. Because mammalian systems respond to bacterial endotoxins with secretion of TNF, IL-1, glucocorticoids, G-CSF and GM-CSF, our results shed additional light on this highly regulated cytokine network and revealed a novel role for GM-CSF. PMID- 8468486 TI - Effect of docosahexaenoic acid on the generation of platelet-activating factor by eosinophilic leukemia cells, Eol-1. AB - Human eosinophilic leukemia (Eol-1) cells were examined for their ability to generate platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine) (PAF) and the effect of supplementation of docosa-hexaenoic acid (C22:6n-3) (DHA) on the PAF synthesis was explored in relation to the fatty acid composition of phospholipids and the liberation of arachidonic acid (C20:4n-6 AA). Although undifferentiated cells did not produce PAF, the exposure of IFN gamma differentiated Eol-1 to generate PAF in response to the Ca-ionophore. In addition, the IFN-gamma-treated cells acquired the ability to release free fatty acids, approximately 55% of which was found to be AA. When DHA was supplemented into the culture of Eol-1 for 24 h, PAF production decreased by 40 to 50% at concentrations of 3 to 10 microM. On the other hand, supplementation of 10 microM eicosapentaenoic acid (C20:5n-3) did not significantly decrease PAF production. With the supplementation of 10 microM DHA, DHA levels in phospholipid subclasses, including alkylacylglycerophosphocholine, were greatly increased with concurrent decreases in other unsaturated fatty acids. In these cells, the liberation of AA in response to an ionophore was decreased by 55%. Even when DHA was enriched in phospholipids, DHA release in response to ionophore stimulation was almost negligible, indicating that the DHA moiety of phospholipids is not susceptible to the action of phospholipase A2. Furthermore, DHA supplementation appeared to attenuate phospholipase A2 reaction by some unknown mechanism because the decrease in AA release was much more than that for the AA level in phospholipids. Acetyl-CoA:1-alkylGPC acetyltransferase activity of stimulated cell lysate was also reduced by DHA supplementation but the reduction was much less when compared with that of PAF synthesis or AA release. These results implicated that enrichment of DHA attenuates enzymic reactions for PAF synthesis, mainly the initial reaction catalyzed by AA-specific phospholipase, and thereby reduces PAF synthesis in Eol-1. PMID- 8468487 TI - Agonist-dependent phosphorylation of N-formylpeptide and activation peptide from the fifth component of C (C5a) chemoattractant receptors in differentiated HL60 cells. AB - Attenuation of signaling is a key step in controlling the cytotoxic potential of leukocyte responses to chemotactic factors. Antipeptide antibodies, directed against the N-formyl chemotactic peptide receptor (FPR) and the activation peptide from the fifth component of C (C5a) anaphylatoxin receptor (C5aR) of human neutrophils, were used to analyze the ability of these receptors to be phosphorylated. Our data show that, in granulocyte-like differentiated HL-60 cells, both FPR and C5aR undergo an agonist dose-dependent phosphorylation that reaches completion in less than 2 to 3 min, consistent with the rate and the dose dependent attenuation of signaling in phagocytes. Therefore, phosphorylation might be one of the possible mechanisms involved in the desensitization process of FPR and C5aR. Addition of either C5a or the protein kinase C activator (PMA) did not appear to induce the phosphorylation of FPR in the absence of FMLP or to modulate the phosphorylation of the latter at low concentrations of agonist. In contrast, although FMLP at a saturating concentration barely stimulated the phosphorylation of unoccupied C5aR, it markedly potentiated C5aR phosphorylation in cells exposed to low concentrations of C5a. Moreover, PMA was able to induce C5aR phosphorylation in the absence of agonist, indicating that protein kinase C or protein kinase C-activated kinase(s) could be involved in the phosphorylation of C5aR. Pretreatment of cells with staurosporine, a potent but nonspecific inhibitor of protein kinase C, resulted in the partial inhibition of both FPR and C5aR phosphorylation induced by saturating concentrations of agonist, suggesting that a kinase different from protein kinase C might be mainly responsible for the phosphorylation of these chemotactic receptors. PMID- 8468488 TI - Effects of exogenous eicosapentaenoic acid on generation of leukotriene C4 and leukotriene C5 by calcium ionophore-activated human eosinophils in vitro. AB - Exogenous eicosapentaenoic acid (EPA) has been compared with exogenous arachidonic acid (AA) for its ability to modulate the oxidative metabolism of membrane-derived arachidonic acid by the 5-lipoxygenase pathway in ionophore activated human eosinophils, and for its suitability as a parallel substrate in this pathway. Products were quantitated by specific RIA and tetraene and pentaene leukotrienes (LT) were separated by reverse-phase HPLC. Eosinophils were preincubated with control buffer, exogenous EPA or AA and stimulated optimally with 10 microM calcium ionophore (A23187) for 15 min. Mean generation of LTC4 in the absence of fatty acid was 6.0 = 1.1 ng/10(6) eosinophils (mean = SEM, n = 5). In the presence of EPA, the amount of LTC4 generated rose to peak at 16.5 +/- 1.9 ng/10(6) eosinophils at 10 micrograms/ml EPA and then fell to 8.3 +/- 3.1 ng/10(6) cells at 40 micrograms/ml EPA. The EPA derivative, LTC5 was first detectable at 5 micrograms/ml EPA with 4.8 +/- 1.2 ng/10(6) cells and gradually rose with increasing dose of EPA to be maximal at 40 micrograms/ml with 12.7 +/- 2.2 ng/10(6) cells. Identity of the LTC5 was confirmed by an identical retention time to synthetic LTC5 standard, immunoreactivity to a specific antibody against LTC4 and LTC5 and a typical UV absorbance spectrum. When eosinophils were preincubated with AA and similarly stimulated, LTC4 generation gradually increased from a baseline of 6.7 +/- 0.7 ng/10(6) cells in the absence of fatty acid to reach a maximum of 12.9 +/- 0.8 ng/10(6) cells at 40 micrograms/ml of AA. Total LTC generation was nearly twofold more with cells incubated with EPA than with cells incubated with AA (p < 0.05). Thus, EPA does not suppress LTC generation from eosinophils but stimulates it at lower doses and is a substrate for LTC5 generation. PMID- 8468489 TI - Transforming growth factor-beta mediates IL-1-dependent induction of IL-1 receptor antagonist. AB - Transforming growth factor-beta (TGF-beta) is a potent immunomodulatory molecule that promotes inflammation through recruitment of monocytes and induction of IL-1 and other cytokines. These proinflammatory processes may be modulated by the ability of TGF-beta to induce de novo synthesis and secretion of an IL-1 receptor antagonist (IL-1ra) that binds to and blocks IL-1 receptors. In this study, we show that the addition of TGF-beta to human peripheral blood monocytes induced the sequential transcription of the 1.8-kb mRNA for IL-1 beta and for IL-1ra. The expression of detectable mRNA and synthesis of IL-1 beta peptide routinely preceded that for IL-1ra, suggesting possible dependency of IL-1ra generation on IL-1 beta. Antibody to IL-1 blocked TGF-beta induction of IL-1ra mRNA expression demonstrating an unique IL-1-dependent induction of its own antagonist. Confirmatory evidence that IL-1 participates in the generation of IL-1ra was obtained when exogenously added IL-1 induced and, IL-1 receptor antagonist blocked, IL-1ra transcription. Thus, these data suggest that TGF-beta, after release at a site of inflammation, induces synthesis of IL-1 that participates in the initial cytokine cascade central to an inflammatory response, and then triggers the generation of its own natural inhibitor by autocrine or paracrine pathways. This TGF-beta-induced IL-1-dependent induction of IL-1ra may provide a negative feedback loop, thereby promoting the resolution of an inflammatory response. PMID- 8468490 TI - Monoclonal Ig L chain and L chain V domain fragment crystallization in myeloma associated Fanconi's syndrome. AB - Monoclonal free L chains secreted in immunoproliferative disorders are frequently involved in renal complications, including a specific proximal tubule impairment, the Fanconi's syndrome, which is generally featured by intracellular crystallization of L chain-related material. In a patient with myeloma-associated Fanconi's syndrome, hexagonal crystals (most surrounded by smooth membranes) were found in kidney proximal tubular cells and bone marrow plasma cells and phagocytes. The sequence of the patient's monoclonal kappa-chain was deduced from that of identical kappa-cDNA clones from the tumoral plasma cells. Small protein enriched gel filtration fractions from urine yielded crystals morphologically similar and with the same 60 A periodicity on electron micrographs as those found in the cells. N-terminal sequencing and mass spectrometry studies showed that the crystals contained a 107-amino acid fragment (with a C-terminal lysine) corresponding to the V domain together with a low proportion of the entire kappa chain. In vitro trypsin and pepsin treatment of the native entire kappa-chain yielded a homogeneous V domain fragment which, contrary to other monoclonal kappa chains, was completely resistant to further proteolytic attack. The patient's kappa-chain also displayed an unusual self-reactivity, as demonstrated by a Western blot technique. The peculiar proneness of the V domain to resist proteolysis and to form crystals might prevent the normal cell catabolism of the L chain and lead to crystallization and renal impairment. PMID- 8468491 TI - Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjogren's syndrome. AB - To better define the genetic factors that predispose to primary Sjogren's syndrome (SS), we have used polymerase chain reaction in combination with oligonucleotide probe hybridization and DNA sequencing to analyze HLA-DRB1, DQA1, -DQB1, and -DPB1 alleles in Caucasoid (California), Japanese (Tokyo), and Chinese (Shanghai and Beijing) SS patients. In comparison to local controls in each region, we found: 1) increased frequency of the predicted haplotype HLA DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 in Caucasoid patients (p < 0.001); 2) increased frequency of the predicted haplotype HLA-DRB1*0405-DRB4*0101-DQA1*0301 DQB1*0401 in Japanese patients (p < 0.05); 3) increased frequency of the predicted haplotype DRB1*0803-DQA1*0103-DQB1*0601 in Chinese patients (p < 0.05); and 4) no statistically significant association with DPB1 alleles in any group, although an increased number of Caucasoid and Japanese SS patients possessed DPB1*0301. Comparison of DNA sequences for the three disease-associated haplotypes in these ethnic groups revealed a shared region of predicted amino acids from positions 58 to 69 in the first domain of HLA-DQB1. These results extend previous studies by demonstrating that no single class II allele was associated with 1 degree SS in the different ethnic groups. However, a shared amino acid motif in the DQB1 first domain was present in each disease-associated haplotype. PMID- 8468492 TI - Engraftment and activity of anti-CD3-activated human peripheral blood lymphocytes transferred into mice with severe combined immune deficiency. AB - Human PBL (huPBL) were activated with anti-CD3 mAb in vitro and then were transferred into mice with severe combined immune deficiency (SCID) to determine the effect of activation on engraftment and to determine if the engrafted human cells could provide antitumor effects in mice. Some mice were also treated with human rIL-2 after huPBL transfer. Mice were analyzed 6 to 8 wk after cell transfer and the number of human cells in the peripheral lymphoid organs was determined. Mice receiving anti-CD3-activated huPBL demonstrated a significant increase in the incidence of human T cell engraftment in the periphery as assessed by flow cytometry. Human cells were also detected in the murine thymus after anti-CD3 stimulation indicating that human T cells can migrate to the murine thymus provided that they are activated before the transfer. The transfer of anti-CD3-activated huPBL also resulted in an xenogeneic graft-vs-host reaction manifested primarily by proliferation of murine splenic hemopoietic cells. When SCID mice received the human colon carcinoma HT29, the concurrent transfer of anti-CD3-activated human cells resulted in a significant increase in survival. However, the human cells displayed low cytolytic activity toward human tumor targets when they were recovered from the lymphoid organs of the SCID recipients. Supernatants from the anti-CD3-activated cells were able to inhibit the growth of HT29 in vitro, partly because of the presence of IFN-gamma, suggesting that the human T cells are producing cytokines in vivo that have antitumor effects. Thus, the use of anti-CD3-activated huPBL in SCID mice may be of value for optimizing human cell engraftment in the human/mouse lymphoid chimeras and may be used to evaluate potential anti-neoplastic therapies that employ human effector cells. PMID- 8468493 TI - Serum-IgE-facilitated allergen presentation in atopic disease. AB - The occurrence of facilitated Ag presentation (FAP) was investigated in atopic disease using an in vitro model in which the ability of CD23-expressing EBV-B cells was tested to present Der p II, a major allergen of housedust mite Dermatophagoides pteronyssinus, to cells of autologous Der p II-specific CD4+ T lymphocyte clones. Purified Der p II protein was immune complexed with Ig by preincubation in sera from atopic patients containing Der p II-specific IgE. Incubation of EBV-B cells with these complexes before using the cells as APC results in proliferation of the Der p II-specific T cells at a 1000-fold lower Der p II concentration than required for T cell activation by presentation of uncomplexed Der p II. FAP is not evident using sera from allergic and nonallergic control donors not containing Der p II-specific IgE. FAP is mediated by IgE and not by IgG, because it can be blocked completely by preincubating the serum from atopics with polyclonal anti-IgE and not with polyclonal anti-IgG. After pulsing EBV-B with precomplexed Der p II at 4 degrees C, FAP is as strong as after incubation at 37 degrees C, suggesting that FAP is the result of facilitated trapping of IgE-complexed allergen. CD23 was involved in facilitated trapping of the complexes, because FAP is blocked by preincubation of EBV-B with anti-CD23. In contrast to FAP of Der p II, which was mediated by all Der p II-specific sera tested, only one of four sera containing cat allergen-specific IgE was appropriate to mediate FAP to cat allergen-specific T cell clones. Inasmuch as FAP enables functional presentation of allergen in vivo at doses as low as several nanograms, FAP may contribute to the continuing of chronic allergic reactions in response to minute doses of aeroallergens, especially housedust mite allergens, in the environment. PMID- 8468494 TI - [Treatment of experimental invasive pulmonary aspergillosis in rats with liposomal amphotericin B]. AB - Liposomal amphotericin B was evaluated for toxicity, pharmacokinetic properties and therapeutic efficacy in invasive pulmonary aspergillosis in Sprague-Dawley rats. The protective effect of liposomes against the toxicity induced by repeated amphotericin B infusions was observed in a survival study of rats, thereby allowing higher dosages to be administered. Pharmacokinetic studies showed that liposomes led to high levels of amphotericin B in the spleen and liver. Drug levels in the lung were higher at ten minutes after intravenous injection of liposomal amphotericin B at 20 mg/kg than of free amphotericin B at 1.5 mg/kg. Efficacy was assessed in rats treated with cortisone acetate, fed a low-protein diet and infected transtracheally with 8 x 10(4) Aspergillus fumigatus spores to cause fetal pneumonia and pulmonary bleeding. Dosages of 20 or 4 mg/kg of liposomal amphotericin B, or 1.5 mg/kg of free amphotericin B were administered intravenously to rats once daily for 8 days. Control rats received saline. Twenty mg/kg of liposomal amphotericin B was as effective on survival rate as 1.5 mg/kg of free amphotericin B. However, 4 mg/kg of liposomal amphotericin B was less effective than 1.5 mg/kg of free amphotericin B, prolonging the mean survival time of rats treated with saline, which showed elevation of galactomannan antigen titers of Aspergillus fumigatus in sera and invasive proliferation or mycelia with bleeding in histopathological sections of the lung. We conclude that liposomal amphotericin B reduces toxicity of the drug, thereby increasing the concentration of the drug in the lung by high-dose administration, but decreases the efficacy of the drug in experimental pulmonary aspergillosis. PMID- 8468495 TI - [Sporadic case of hemolytic uremic syndrome associated with verotoxin producing Escherichia coli O2:K1:H7]. AB - Cases of enterohaemorrhagic Escherichia coli (EHEC) are being increasingly reported in Japan. Bacteriological isolation of EHEC has been a constant problem because the organism is shed for a short duration after onset on illness and generally during the prodromal stages. In order to ease the diagnosis of EHEC infections in this country, we have developed a LPS-based solid phase enzyme linked immunosorbent assay for serological diagnosis of the infection. Adequate knowledge on the prevalence of EHEC serogroups in Japan is mandatory for the success of such a diagnostic test. O157 is currently the prominent serogroup associated with EHEC infections in Japan followed by O111, O26 and O128 in that order of prevalence. In February 1992, a 1 year-old infant developed hemolytic uremic syndrome (HUS) 15 days later the prodrome of watery diarrhoea. Stool sample obtained on day 15 was cultured for detection of EHEC. Ten colonies of E. coli picked from MacConkey agar plate were examined by the polymerase chain reaction (PCR) using primers specific for both verotoxins (VT1 and VT2). Of the 10 colonies, only one was positive for the VT2 gene. The strain was confirmed to be cytotoxic on cultured Vero cells. The strain agglutinated with antisera of E. coli O2, K1 and with H7 serogroups. As of date, none of such strains of O2:K1:H7 EHEC has been reported in Japan. The patient's sera was found to be positive for antibodies against LPS from the homologous isolate as well as against VT2. The patient recovered uneventfully from HUS 40 days after the onset of the disease and was discharged from the hospital. PMID- 8468496 TI - [Epidemiology of sporadic pediatric enteritis patients due to verotoxin-producing Escherichia coli]. AB - We tried to isolate verotoxin-producing Escherichia coli (VTEC) from 323 sporadic pediatric enteritis patients who came to three clinics in the Fukuoka area. We used the sorbitol-MacConkey medium for the isolation of VTEC O157:H7. For non O157 VTEC strains we used the V1/PECS method. VT/PECS method was applied. VTEC strains were isolated from three patients (0.9%). None of the patients were seriously, ill or developed the hemolytic uremic syndrome. The three patients were all seen in the summer season, July and August. O157:H7 strains were isolated from two patients, and O145:NM from one. This study showed that sporadic enteritis cases due to VTEC exist in the Fukuoka area. In the future a rapid and easy method for the detection of VT or VTEC should be developed and commercialized to proceed with epidemiological studies of VTEC infections throughout Japan. PMID- 8468497 TI - [Biological characters of the clinically isolated strains of Escherichia coli O157:H7 in Canada]. AB - Biological characters of enterohemorrhagic Escherichia coli (EHEC) strains isolated from food poisoning cases in Canada, 1987-1988 were examined in comparison with that isolated in Saitama, 1990. The Saitama strain was found to belong to biotype I, and biotypes I and II were found in Canada. Most of the strains including the Saitama strain were found to have siderophilins suggesting their advantageous growth in vivo. An enteroinvasive strain with 140 megadalton (Md) plasmid and two colicinogenic strains with 4.8 Md plasmids were detected. All strains were found to have 60 Md plasmids. This plasmid might be specific for this serotype. A few strains were resistant to streptomycin (SM) and/or tetracycline (TC), and a strain transferred its SM-TC resistances by conjugation. Many strains including the Saitama strain were found to produce vero cytotoxin (VT) types 1 and 2 (VT1 and VT2). A few type 2 and untypable toxin producing strains were also detected. VT titers produced by untypable toxin producing strains were over 10 times lower than those by other strains. High annealing temperature for PCR amplification of VT1 gene and a variety of annealing temperatures of VT2 gene suggested that the nucleotide sequences for VT1 gene were well preserved, but that those for VT2 might have some mutations. PMID- 8468498 TI - [Differences in susceptibility of Helicobacter pylori to macrolide and other antibiotics in tests using blood agar and albumin agar]. AB - Minimum inhibitory concentrations (MICs) of penicillin G, cefazolin, tetracycline, chloramphenicol, four aminoglycosides, and seven macrolides against Helicobacter pylori strains were determined on Brucella agar supplemented with bovine serum albumin fraction V (albumin agar) and compared with those on blood agar. MICs of the macrolides against H. pylori determined on albumin agar were markedly lower than those found with blood agar. The susceptibilities of 26 H. pylori strains to the macrolides were estimated from the MIC50 values determined on blood agar and albumin agar, which were 0.39 and < or = 0.05 micrograms/ml for erythromycin, midecamycin and rokitamycin, 3.13 and 0.10 micrograms/ml for clindamycin, 1.56 and < or = 0.05 micrograms/ml for josamycin, 1.56 and 0.10 micrograms/ml for kitasamycin, and 0.10 and < or = 0.05 micrograms/ml for roxithromycin, respectively. However, the MICs of other antibiotics against H. pylori and of all antibiotics against two reference Campylobacter strains differed minimally between values obtained on blood agar and albumin agar. PMID- 8468499 TI - [Study of local immune response in mice with an impaired chemotaxis of neutrophils--in Pseudomonas aeruginosa induced experimental urinary tract infection]. AB - Experimental ascending urinary tract infection was induced by transurethral instillation of Pseudomonas aeruginosa in mice whose neutrophilic chemotactic activity was suppressed by administration of colchicine, and we investigated the time course fluctuation of local immune response at the infected sites in terms of immune response cells as compared with that in normal mice. In comparison with that in normal mice, a significant suppression was noted in the chemotactic activity of the peritoneal exudating neutrophils when colchicine at a dose of 0.02 mg/mouse was administrated a total of 4 times, namely, 1, 3 and 5 days, and 6 hours before infection (the day of assessment). When experimental ascending urinary tract infection was induced by P. aeruginosa, markedly increased susceptibility to bacterial infection was noted in mice with an impaired chemotaxis of neutrophils (impaired neutrophilic chemotaxis group) as compared with that in normal mice (control group). Apparent infiltration of neutrophils was recognized one day after infection in the control group by the time course observation of the immune response cells at the sites of infection while hardly any infiltration was observed in the impaired neutrophilic chemotaxis group one day after infection. In other words, the cellular infiltration into an infected site was conceivably obstructed when the chemotactic activity was impaired. On the other hand, macrophages in the impaired neutrophilic chemotaxis group demonstrated marked infiltration as compared with that in the control group one day after infection, and such infiltration remained on the same higher level thereafter. As for T and B cells, an increased ratio was noted in helper T cells and early infiltration in IgG positive B cells 3 days after infection and onward when compared with the control group. It was therefore suggested that other immune response cells compensated for the infiltration of neutrophils when their chemotactic activity was obstructed, and that these cells on the whole possibly responded toward the preservation of their protective mechanism against infection. PMID- 8468500 TI - Chronic melioidosis: a report of the first case in Japan. AB - A 41-year-old Japanese male with uncontrolled diabetes mellitus and alcoholic liver dysfunction developed melioidosis after his business trip to Indonesia and Singapore in 1988. His disease started with spiked fever on the following day after extraction of a tooth, and a liver abscess developed, followed by abscesses in the spleen and in the subphrenic space. In spite of splenectomy and intensive antimicrobial treatments for three months, he developed parotitis, prostatitis, and abscess of the right submandibular gland at 5 to 16-month interval. Pseudomonas pseudomallei was isolated from the blood and pus from each abscess. The lung was not involved. At present, he has returned to work, with continued intravenous instillation of imipenem/cilastatin. PMID- 8468501 TI - [A case of Legionnaires' disease due to aspiration of hot spring water and isolation of Legionella pneumophila from hot spring water]. AB - We report a case of fulminant pneumonia that was due to aspiration of contaminated hot spring water and was not affected by beta-lactam antibiotics. We suspected that the patient had Legionnaires' disease and treated the clinical symptoms with erythromycin. Legionellaceae could not be isolated from sputum or lung biopsy material, but an elevated titer to Legionella pneumophila serogroup 4 was found by indirect immunofluorescence test. We diagnosed the patent as having Legionnaires' disease with improved clinical symptoms. Furthermore, we went to the hot spring that he visited and tried to isolate Legionellaceae. Hot spring water was collected from the bathroom and water, hot water, and shower water from the guest-room. After using a low-pH method, samples were cultured on BCYE alpha medium. Serogroups are classified by agglutination method with immune rabbit serum. As a result, we successfully isolated Legionella pneumophila serogroup 4 from hot spring water (42 degrees C) from the bath. No bacteria could be isolated from the other samples. Therefore, we believe that this case of Legionnaires' disease was caused by aspiration of contaminated hot spring water. The infection route of Legionnaires' disease is unclear. There are no previous reports of isolation of Legionellaceae from Japanese hot springs. This case would provide important information when considering the infection route of Legionnaires' disease in Japan. PMID- 8468502 TI - [Prevalence of HIV infection among stable female partners of seropositive men]. AB - Prevalence of HIV transmission to female sexual partners of seropositive men is not known yet. In order to know the condition in Japan, 11 HIV-seropositive men (25-42 years old; mean +/- SD, 32.5 +/- 6.0) and their stable female partners (24 42 years old; mean +/- SD, 31.3 +/- 6.0) were analyzed. Seropositive men consisted of seven hemophiliacs including a hemophiliac with intravenous drug abuse, three men who acquired HIV infection through heterosexual contact, and a man with intravenous drug abuse. Six of them were asymptomatic carriers, two had AIDS-related complex, and three had AIDS. All of the female partners had no risk factors other than sexual contact with their stable, seropositive male partners, except one who used to inject intravenous drug. Four of 11 female partners (36%) were found to be infected with HIV. All of the male partners of infected females had AIDS or AIDS-related complex, and had CD4 counts fewer than 100 cells/microliters. Asymptomatic carriers and men with CD4 counts more than 200 cells/microliters did not transmit HIV to their partners: rate of transmission of HIV by symptomatic men was significantly higher than that by asymptomatic men (p < 0.01), and the rate by men with CD4 counts fewer than 100 cells/microliters was also significantly higher than that by men with larger CD4 counts (p < 0.01). HIV p24 antigen was measured in 10 of 11 seropositive men. The antigen was positive in four men, and negative in six.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468504 TI - Guide to the use of hyperthermic equipment. 1. Capacitively-coupled heating. PMID- 8468503 TI - Role of cellular membranes in hyperthermia: some observations and theories reviewed. AB - We have re-examined critically the evidence for and against the involvement of membranes in determining the response of cells to acute and chronic heat stress. Although frequently dismissed by many in the past, we believe that the bulk of evidence presented supports the view that physical and compositional alterations of membrane lipid components, both during and subsequent to heat exposure may, at least in part, account for cell adaptation, malfunction and lethality. Our primary goal in this review is to generate renewed interest in testing the validity of this hypothesis. PMID- 8468505 TI - Modification of human tumour and normal tissue pH during hyperthermic and normothermic antiblastic regional isolation perfusion for malignant melanoma: a pilot study. AB - Human tumour and normal tissue pH were investigated during hyperthermic and normothermic antiblastic regional isolation perfusion and the effects of vascular occlusion, artificially induced hypoxia, hyperglycaemia, haemoglobin level of the perfusate and hyperthermia on tumour and normal tissue pH were evaluated. A pilot study was performed on 10 patients, with locally inoperable recurrent and primary malignant melanoma of the leg. The treatment consisted of a regional isolation perfusion with hyperthermia (120 min at 42-43 degrees C), at femoral level, followed by a normothermic regional isolation perfusion with Melphalan (60 min at 37-38 degrees C), at iliacal level, 7-10 can be distinguished: (1) first ischaemic anoxia period; (2) extracorporeal circulation, during which the leg is heated to the desired temperature, after which either hyperthermia or Melphalan is applied; (3) second ischaemic anoxia period. During the anoxia periods the large vessels that supply the leg are temporarily clamped and the effects on tissue pH can be investigated. During extracorporeal circulation, high-dose glucose can be administered to the isolated leg, to acutely decrease tumour tissue pH. Such a decrease is expected to sensitize tumours to hyperthermia, when applied immediately prior to or during heating. At the beginning of the treatment the mean tumour pH was significantly lower than normal tissue pH (7.14, with a mean tumour volume of 39.2 cm3, and 7.38, respectively; p < 0.01). During the perfusions with hyperthermia and Melphalan, tissue pH decreased by -0.41 units and -0.20 for tumour, and -0.11 units for normal tissue, respectively (all statistically significant). The two anoxia periods accounted for approximately half of the net decrease. During these periods tumour pH appeared to decrease more selectively, although there was great variation. The other investigated modalities, such as hyperglycaemia and hyperthermia, also decreased tissue pH, but to a lesser extent. However, a combination of more than one modality caused a larger decrease than a single one, but no preference for tumour could be detected. Before the second perfusion mean tumour pH was significantly increased by 0.14 units, and was no longer significantly different from normal tissue pH in the course of the regional isolation perfusion. This could be the reflection of the reduced tumour volume (by 30%, n.s.). Similar pH changes occurred during this Melphalan perfusion, but they were less pronounced since the total treatment time was shorter. Summarizing, tumour pH can be decreased more than normal tissue pH in the course of the regional isolation perfusion. In particular, vascular occlusion appeared to be tumour pH selective.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8468506 TI - Problems associated with CT-guided catheter insertions. AB - From October 1987 to August 1991 a total of 141 closed-tip catheters were inserted into deep-seated or half-deep-seated tumours in 95 treatment areas. Most of the catheters (n = 79) were implanted in the pelvic region. In 139 punctures no clinical evidence of bleeding was seen. A transient blood loss was evident in only two patients. In addition, no nerve injury was observed. The problems with 141 implanted catheters were evaluated. Nineteen catheters (13%) were lost during the treatment series. In five displacement of the catheters was verified by repeat CT scans during the whole treatment. Eight catheters had to be removed due to infection. In two patients with advanced disease who were receiving a combination of chemotherapy and hyperthermia a strong inflammatory response was evident. Another patient developed an acute pancreatitis after catheter insertion. No metastasis in the invasive tracks has been seen in the follow-up period. In conclusion the insertion of closed-tip catheters by CT guidance is a sure and well-tolerated method. There were a few problems only with the implanted catheters throughout the whole treatment series. PMID- 8468507 TI - Pre-clinical evaluation of a microwave planar array applicator for superficial hyperthermia. AB - Multi-element hyperthermia applicators have an advantage over single-aperture devices in that the power deposition pattern across the applicator surface may be adjusted to improve the resultant temperature distribution. This capability can be used to compensate for irregular tumour geometry as well as heterogeneity of thermal and power absorption parameters within the tissue. This paper evaluates the first commercially available microwave system of this type designed for superficial hyperthermia. The applicator (16-element planar array, 915 MHz, 15.2 x 15.2 cm footprint) was evaluated by the following: (1) measuring absolute SAR distributions in muscle-equivalent liquid phantom with an intervening 1 cm thick layer of fat phantom by scanning a calibrated E-field sensor, and (2) power output measurements using calorimetric methods. The SAR distributions measured for each individual aperture exhibited significant irregularities and differing power deposition patterns. A priori knowledge of these different power deposition characteristics was used to provide appropriate illumination schemes which could be used as initial starting points for producing clinically useful power deposition patterns. Measurements of these composite patterns demonstrate the adjustable nature and flexibility of the heating capabilities of this applicator, which includes 50% iso-SAR coverage that can be extended to the applicator perimeter. This clearly illustrates the clinical utility and potential advantages of this system over single-aperture devices for superficial hyperthermia. PMID- 8468508 TI - Changes in electrical impedance of skeletal muscle measured during hyperthermia. AB - The electrical impedance of rat skeletal muscle was measured from 100 Hz to 40 MHz during the application of typical hyperthermia heating regimens. Trials were performed employing freshly excised tissue heated to target temperatures from 39.5 to 50 degrees C. Abrupt and rapid decreases in the low-frequency beta dispersion occurred very shortly after reaching hyperthermia temperatures. These rapid decreases continued at a rate and to an extent dependent upon the target temperature, and then, as heating continued, abruptly changed to a much slower rate which continued indefinitely. The initial rapid changes were associated with microscopically observed muscle fibre rounding and radial shrinkage, with accompanying increasing interstitial oedema. The subsequent slow changes were associated with a slow histolysis. The time- and temperature-dependence of the rapid resistivity changes evidenced similarities to typical hyperthermia endpoint responses. An Arrhenius analysis of the rate of the resistivity changes yielded a break at 43 degrees C, with activation energies of 36.1 and 58.3 kcal/mol above and below this break. Preliminary in vivo impedance data displayed qualitative similarities to the excised tissue findings. PMID- 8468509 TI - Small cylindrical ultrasound sources for induction of hyperthermia via body cavities or interstitial implants. AB - In this study, small (outside diameter 1 mm) cylindrical ultrasound sources were investigated for induction of hyperthermia in tumours. These ultrasound transducers could be placed in small-diameter body cavities, or they could be used interstitially in brachytherapy catheters. The ultrasound field measurements showed that the field is fairly uniform as a function of the length of the applicator except at the ends where sharp peaks were located. However, there were significant field variations as a function of rotation angle around the transducers. The degree of these non-uniformities varied from transducer to transducer, and also as a function of frequency. The temperature measurements in vitro perfused kidneys showed that therapeutic temperature elevations could be induced in perfused tissues. The radial extent of the therapeutic zone could be increased by circulating water around the applicators, thus avoiding high temperatures on the applicator surface. It was also shown that some control over the temperature distribution along the length of the applicator could be achieved by using a two-element applicator. An array of four applicators implanted in a square pattern with the spacing of 25 mm between the catheters, was able to heat the tissue volume inside of the implant. The results showed that these small ultrasound applicators may offer significant improvement over existing techniques by increasing the penetration depth and the control over the power deposition pattern. PMID- 8468510 TI - Synergism between alkylating agent and cis-platin with moderate local hyperthermia: the effect of multidrug chemotherapy in an animal system. AB - The combined effect of multidrug chemotherapy given in combination with hyperthermia was investigated using early-generation isotransplants of a spontaneous fibrosarcoma, FSa-II in C3Hf/Sed mice. Combinations of various types of chemotherapeutic agents, including alkylating agents, cyclophosphamide (CY) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU); antibiotics, bleomycin (BLM) and mitomycin C (MMC); an antimetabolite, 5-fluorouracil (5FU); and a platinum complex, cis-diamminedichloroplatinum(II) (cDDP), were examined using the tumour growth (TG) time assay. Simultaneously, the effect of glucose on the response to thermochemotherapy was investigated. Graded doses of the multidrugs were given i.p. immediately before hyperthermia with or without a glucose dose of 5 g/kg given i.p. 60 min before hyperthermia. Hyperthermia was given by immersing the tumour-bearing murine feet into a water bath set at 41.5 +/- 0.05 degrees C for 60 min. Dose-response curves were obtained between the TG time and drug dose. The thermal enhancement ratio (TER) was expressed as a ratio of the slope of the dose response curve obtained at 41.5 degrees C to that obtained at room temperature. To evaluate normal tissue damage, the number of white blood cells (WBC) was counted from a day before treatment to the 21st day after treatment. A substantial thermal enhancement of the anti-tumour effect was observed in all five multidrug regimens tested. Glucose administered prior to thermochemotherapy further enhanced the antitumour effect. The TER was largest for the combination of CY+cDDP (TER was 5 without glucose). The second largest TER was obtained for a combination of CY+cDDP+MMC (TER was 4.1 without glucose and 6.5 with glucose). The antitumour effects of these two combinations were synergistic at a test elevated temperature only. No synergistic effect was found at room temperature for any of the drug combinations tested. The smaller TERs were observed in the treatment regimens that included 5FU. In general, a decrease in the number of WBC following multidrug chemotherapy was slightly less than that following the individual drugs. PMID- 8468511 TI - Tumour pH drop after cryotreatment and enhancement of hyperthermia antitumour effect. AB - Our previous study demonstrated a selective drop of pH, PO2 and blood flow in tumours under induced hyperglycaemia that enhanced the antitumour effect of hyperthermia. However, there are contraindications restricting the use of hyperglycaemia. Cryotreatment, as a method of altering tumour microphysiology similar to hyperglycaemia, was investigated. Guerin carcinoma pH was measured after cryotreatment (-15 to -20 degrees C at the tumour and normal tissue boundary; -110 to -120 degrees C at the cryoinstrument tip). It was determined that tumour pH immediately after complete tumour thawing (10 degrees C) was 6.08 (range 5.5-6.3), by 2 h it was 6.34 (range 6.2-6.4), by 4 h it was 6.42 (range 6.1-6.8) and by 24 h it was 6.54 (range 6.3-6.6). Complete tumour regression (%) and survival of rats with both the tumour regrowth and the partial tumour regression (days) after a single treatment were as follows: control -zero, 28 +/- 4; hyperthermia (2450 MHz, 43 degrees C, 60 min) -zero, 30 +/- 3; cryotreatment 14, 35 +/- 5; cryotreatment+hyperthermia -41, 46 +/- 5. It is planned to use combined cryotreatment+hyperthermia in a clinical trial for certain accessible tumours. PMID- 8468512 TI - A comparison of the effect of hyperthermia on DNA polymerase in hamster and human glioma cells. AB - The hyperthermia response of two human glioma cells lines (87MG and 373MG) was compared to the CHO cell line for cell killing and DNA polymerase inactivation. Glioma cells were found to be more thermally resistant than CHO cells over a temperature range of 41-46 degrees C. Inactivation of polymerase alpha and beta by hyperthermia was also more resistant in glioma cells than in CHO cells. The relative order of resistance for both killing and polymerase inactivation was 373MG > 87MG > CHO. While polymerase inactivation correlated with cell killing at high thermal doses, such correlation at low doses was absent; i.e. thermal killing was characterized by survival curves with shoulders while polymerase inactivation was not. Thus at low thermal doses the mechanism of thermal cell killing is probably not related to the degree of polymerase inactivation. Arrhenius analysis of the survival data showed that the inactivation energy for the glioma cells was 133-135 kcal/mol. The inactivation energies of alpha and beta polymerase were also evaluated and were 102-104 and 140-146 kcal/mol, respectively. Further analysis of the temperature-time relationship of hyperthermia treatment resulting in 50% cell kill showed the degree of polymerase beta inactivation to be a good indicator of thermal dose. PMID- 8468514 TI - [Interaction of DNA with nuclear skeletal structures]. PMID- 8468513 TI - Abnormal rheological response of erythrocytes caused by nitroimidazoles and hyperthermia. AB - The aim of the present study was to investigate the response of erythrocytes to hyperthermia in combined treatment with nitroimidazoles. The efficiency of nitroimidazoles and physical agents on the rheological response of erythrocytes was measured by the viscosimetric-diffractometric method in a continuous osmotic gradient with constant shear stress of 100 dyn/cm2. We found that three newly synthesized dinitro- or nitroimidazole derivatives caused oxidative damage of erythrocytes in aerobic conditions. Nitroimidazole structure-dependent decrease of erythrocyte deformability was accompanied by oxidation of haemoglobin and depletion of reduced glutathione, lipid peroxidation and alteration of membrane structure indicated by a decrease of the ANS fluorescence intensity and increased production of MDA. Heat treatment per se (from 42 to 45 degrees C) only slightly decreased the erythrocyte deformability, but markedly enhanced the structure dependent effect of nitroimidazoles. Erythrocytes heated at 45 degrees C with dinitroimidazole derivative III lost their deformability without haemolysis. Dithiothreitol used in combination with nitroimidazoles during a heating period to 43.5 degrees C protected cell deformability entirely, indicating an important role for disulphide bond formation in membrane proteins submitted to oxidative stress and hyperthermia. PMID- 8468515 TI - [Processing enzymes for precursors of biologically active peptides and proteins: Kex2-like endoproteases in higher eukaryotes]. PMID- 8468516 TI - [Transcription factor C/EBP family]. PMID- 8468517 TI - [Evaluation of universities by their accomplishment on life science]. PMID- 8468518 TI - [Estrogen synthetase (P-450 . aromatase) as a regulatory factor concerning sexual differentiation of brain and sexual behavior--physiological functions and regulation of gene expression of aromatase]. PMID- 8468519 TI - [Role of polyamines in cell proliferation and differentiation]. PMID- 8468520 TI - Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. PMID- 8468521 TI - Clofibrate elevates enzyme activities of the tricarboxylic acid cycle in rat liver. AB - Activities of the tricarboxylic acid cycle enzymes were measured in subcellular fractions of liver from rats that had been fed clofibrate for 3 weeks. Large changes in these activities per gram tissue were found in the large particle fraction, which also showed an increase in total protein concentration of 76% under clofibrate treatment. The three regulatory enzymes of the cycle, namely citrate synthase, NAD(+)-linked isocitrate dehydrogenase, and 2-oxoglutarate dehydrogenase were significantly enhanced by 24% (P < 0.02), 54% (P < 0.02), and 153% (P < 0.005), respectively. Fumarase and malate dehydrogenase rose by 71% (P < 0.005) and 95% (P < 0.02), whereas succinate dehydrogenase remained unchanged. Enhancement of the citrate synthase, NAD-isocitrate dehydrogenase, and 2 oxoglutarate dehydrogenase may play a role in decreasing intracellular availability of acetyl-CoA for lipid metabolism. PMID- 8468522 TI - Carbohydrate composition of protein and lipid components in sialic acid-rich and poor low density lipoproteins from subjects with and without coronary artery disease. AB - Low density lipoprotein (LDL) from patients with coronary heart disease (CHD) caused 78-286% increase in accumulation of cholesterol in human aortic subendothelial cells compared to 2-17% caused by LDL from normal subjects. Ricin Sepharose affinity chromatography was used to separate LDL into two subfractions, one sialic acid-rich (SAR) and the other sialic acid-poor (SAP). SAP-LDL from CHD patients caused 156-307% increase in accumulation of cellular cholesterol, whereas SAR-LDL from these patients caused only 14-21% increase. SAP-LDL from normal healthy subjects caused 50-86% increased accumulation, whereas their SAR LDL induced only 2-12% increase. Carbohydrate analysis of SAP-LDL protein isolated from four CHD patients revealed mean values of 59, 25, 61, and 11 nmoles of N-acetyl glucosamine, galactose, mannose, and sialic acid per mg protein, respectively. Mean values for SAR-LDL protein from these patients were 59, 31, 77, and 24 nmol/mg protein, respectively. Analysis of SAP-LDL protein from four normal healthy subjects indicated respective mean values of 58, 29, 72, and 22 nmol/mg, whereas SAR-LDL protein from normals contained 59, 29, 72, and 29 nmol/mg. The carbohydrate content of LDL lipids represents about 25% of the total carbohydrate present in the lipoprotein. The mean values for SAP-LDL lipids from four CHD patients were about 2, 2, 18, 18, and 2 nmol/mg protein for N-acetyl galactosamine, N-acetyl glucosamine, galactose, glucose, and sialic acid, respectively. The mean values for SAR-LDL lipids from these patients were 3, 4, 34, 41, and 5 nmol/mg, respectively. Analysis of SAP-LDL lipids from four normal healthy subjects indicated respective mean values of 4, 6, 30, 31, and 3 nmol/mg, whereas SAR-LDL lipids from these subjects contained 6, 9, 41, 46, and 7 nmol/mg. These results suggest that the different biological properties of SAR-LDL and SAP LDL are related to their different carbohydrate compositions. PMID- 8468523 TI - Pharmacologic consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin beta-tigogenin cellobioside (CP-88818; tiqueside). AB - Natural and synthetic saponins inhibit cholesterol absorption and reduce plasma cholesterol levels in experimental animals and are therefore of potential pharmacologic utility in the treatment of hypercholesterolemia. To determine the effects of this class of compounds on cholesterol absorption and metabolism, we evaluated the effects of the synthetic saponin, beta-tigogenin cellobioside (tiqueside; CP-88818), on male golden Syrian hamsters. When administered as either a single oral bolus or as a dietary supplement for up to 2 weeks, tiqueside inhibited cholesterol absorption in a dose-dependent manner in both the presence and absence of dietary cholesterol. Administration of tiqueside to chow fed hamsters as a 0.2% dietary supplement (150 mg/kg per day) for 4 days resulted in a 68% decrease in intestinal cholesterol absorption with no change in either bile absorption or cholesterol 7 alpha-hydroxylase activity, suggesting that tiqueside inhibits cholesterol absorption without interfering with enterohepatic bile acid recirculation. Under these conditions, hepatic cholesterol levels were also reduced in a dose-dependent manner. Hepatic cholesterol reduction was highly correlated with cholesterol absorption inhibition, and induced compensatory increases in both hepatic HMG-CoA reductase activity and hepatic low density lipoprotein (LDL) receptor levels. Compensatory increases in intestinal HMG-CoA reductase activity were also noted after tiqueside administration, and are consistent with a luminal mechanism for tiqueside action. As a consequence of these changes to cholesterol metabolism, tiqueside administration induced plasma cholesterol reductions that were highly correlated with both hepatic cholesterol reduction and cholesterol absorption inhibition. Tiqueside also produced comparable plasma cholesterol lowering in a variety of other species fed either cholesterol-free diets (hamster, rat, mouse, dog) or cholesterol-containing diets (hamster, rat, rabbit, mouse, cynomolgus monkey, rhesus monkey, SEA quail) indicating the ubiquity of tiqueside action. For all species evaluated except the dog, the reduction in plasma cholesterol was due primarily to a reduction in circulating non-HDL cholesterol levels with little or no change in HDL cholesterol levels. Taken together, these results indicate that inhibition of cholesterol absorption by tiqueside produces profound effects on cholesterol metabolism without affecting bile acid metabolism, and that these changes lead to reductions primarily in plasma non-HDL cholesterol concentrations. The synthetic saponin, tiqueside, may thus represent a prototypical form of therapy for the treatment of hypercholesterolemia. PMID- 8468525 TI - Long-term fatty acid modification of endothelial cells: implications for arachidonic acid distribution in phospholipid classes. AB - Human umbilical vein endothelial cells were cultured in various fatty acid modified media until equilibrium conditions were reached (7-8 days). The effects on the fatty acid composition of phospholipid classes and on the metabolism of arachidonic acid (20:4(n-6)) were studied. The results showed that in every phospholipid class large changes in fatty acid composition, including 20:4(n-6) content, were induced by long-term modification with unsaturated as well as saturated fatty acids. However, the mean levels of saturated and unsaturated fatty acids per phospholipid class remained relatively constant, except for cells modified with oleic acid, which showed an increase in monounsaturated fatty acids at the expense of both saturated and polyunsaturated fatty acids. The rate of incorporation of radiolabeled 20:4(n-6) in endothelial lipids was not influenced by long-term fatty acid modification. Cells modified with 20:4(n-6) (having a high 20:4(n-6) content) tended to "store" excess 20:4(n-6) as the elongated product 22:4(n-6) mainly in phosphatidylserine and ethanolamine phospholipids. On the other hand, endothelial cells modified with 20:5(n-3) (having a low 20:4(n-6) content) differed typically from other fatty acid-modified cells by a relatively high level and high incorporation rate of 20:4(n-6) in phosphatidylinositol, with a low extent of elongation. These results indicate extensive homeostatic control of membrane unsaturation in each phospholipid class and economical control of 20:4(n-6) content in all modified endothelial cells, irrespective of a considerable variation of 20:4(n-6) levels in cellular lipids. Moreover, the observed maintenance of a critical level of 20:4(n-6) in phosphatidylinositol, when 20:4(n-6) supply was strongly decreased, may be important for maintaining proper signal transduction upon endothelial cell stimulation. PMID- 8468524 TI - Lipoprotein lipase synthesis and secretion: effects of concentration and type of fatty acids in adipocyte cell culture. AB - Fatty acids (FA) were added to differentiating chick adipocytes to study their effects on the synthesis and secretion of avian lipoprotein lipase (LPL). Oleate (18:1n-9), eicosapentaenoate (EPA, 20:5n-3), and linoleate (18:2n-6) were complexed to fatty acid-free bovine serum albumin (BSA) and separately added to cells in RMPI-1640 media containing 0.5% delipidated hen serum. LPL secretion in the presence of 10 U/ml heparin was used as a means of estimating LPL synthesis. FA from 50 microM to 165 microM depressed LPL secretion for cells exposed to 20:5n-3 and 18:2n-6. The decrease in adipocyte LPL secretion was only observed with chronic administration of FA. In other experiments, the rate of LPL synthesis was estimated by incorporation of radiolabel (Tran 35S-label) in cells exposed to 50 microM FA. Total radioactivity incorporated into LPL, expressed as a percentage of total trichloroacetic acid (TCA)-precipitable radioactivity, was not affected in cells fed 18:1n-9 but was significantly decreased for cells fed 20:5n-3 (45%) or 18:2n-6 (67%) relative to controls given equimolar BSA (33 microM). Abundance of LPL message in similarly treated cells also decreased for cells incubated with 20:5n-3 or 18:2n-6 (35%) relative to controls and 18:1n-9 treated cells. A decrease in adipocyte LPL secretion was also observed with administration of lipoprotein (d < 1.006 g/ml) enriched in n-3 and n-6 fatty acids. LPL secretion of cells incubated with n-3 enriched lipoprotein at 50 microM and 75 microM triglyceride fatty acid equivalents was significantly greater than that of cells incubated with n-6-enriched lipoprotein. Interestingly, at the same concentrations of triglyceride fatty acids, lipoproteins enriched with n-9 fatty acids had no effect on LPL secretion relative to controls. These studies document that in cultured avian adipocytes, LPL secretion, synthesis, and level of message are decreased by chronic administration of n-3 and n-6 fatty acids. In contrast, in adipocytes supplemented with oleic acid there was no effect on LPL synthesis and secretion. PMID- 8468526 TI - Metabolism of sulfonate analogs of ursodeoxycholic acid and their effects on biliary bile acid composition in hamsters. AB - The metabolism of sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate was studied in hamsters. In bile fistula animals these sulfonate analogs of ursodeoxycholic acid were absorbed mainly from the terminal ileum and secreted rapidly into the bile without biotransformation or conjugation. After oral administration, the sulfonate analogs were excreted in the feces at the same rate as chenodeoxycholic acid and its metabolic products. The intestinal microorganisms transformed chenodeoxycholic acid largely into lithocholic acid; the sulfonate analogs were completely resistant to biotransformation. After a 2-week feeding period, the sulfonate analogs of ursodeoxycholic acid accounted for 24.0% and 16.9% of total biliary bile acids. These sulfonates did not affect the proportions of the natural bile acids in the bile, and the ratio of glycine-conjugated bile acids to taurine-conjugated bile acids was not altered by feeding the sulfonates. In contrast, when ursodeoxycholic acid was fed, the proportions of the natural bile acids and the glycine/taurine ratio were changed. These results suggest that the sulfonate analogs had no profound effect on endogenous bile acid metabolism and did not cause a depletion of the hepatic taurine pool during enterohepatic circulation. The sulfonates had no effect on intestinal cholesterol absorption and serum cholesterol levels. PMID- 8468527 TI - Cholesteryl ester transfer protein and high density lipoprotein responses to cholesterol feeding in men: relationship to apolipoprotein E genotype. AB - The apolipoprotein (apo) E isoform is an important determinant of the plasma lipoprotein distribution of apoE and of the metabolism of apoE-containing lipoproteins. We have determined the effects of apoE genotype on the plasma lipoprotein response to cholesterol feeding in 30 young normal male subjects (5 E3/2, 11 E3/3, 14 E4/3) under rigorously controlled dietary conditions. Two diets, differing only in cholesterol content (low cholesterol (LC): 80 mg cholesterol/1000 kcal and high cholesterol (HC): 320 mg cholesterol/1000 kcal), were compared using a random crossover design. At the end of the HC as compared to the LC period, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and HDL2-C increased by an average of 15%, 21%, 7%, and 23%, respectively, for the three genotype groups combined (P < 0.001 for each). The LDL-C response to dietary cholesterol did not differ among the apoE genotypes. However, the increase in HDL-C varied significantly according to the apoE genotype (E3/2: 0 change, E3/3: +4%, E4/3: +12%; P < 0.05). The plasma cholesteryl ester transfer protein (CETP) response to cholesterol feeding also differed amongst the three apoE genotype groups (E3/2: +37%, E3/3: +18%, E4/3: +9%) (P < 0.05). ApoE genotype has significant and opposite effects on plasma CETP and HDL-C responses to dietary cholesterol in men. PMID- 8468528 TI - Preferential association of apolipoprotein E Leiden with very low density lipoproteins of human plasma. AB - Apolipoprotein (apo) E Leiden is a rare variant of human apoE characterized by defective receptor binding and associated with dominant transmission of type III hyperlipoproteinemia. In heterozygotes, apoE Leiden is present in higher concentrations in both total plasma and very low density lipoproteins (VLDL) than the other apoE allele product. In the present study we analyzed cell expression and plasma lipoprotein association of apoE Leiden to determine whether the unequal concentration of the two apoE allele products could be explained by differences in secretion rate from the hepatocyte or by preferential association with VLDL. We transfected the rat hepatoma cell line McA-RH7777 with apoE Leiden or normal human apoE3, and studied their secretion and media distribution. In pulse-chase experiments, the secretion of apoE Leiden was comparable to that of both human apoE3 and rat endogenous apoE, approaching 100% in 90 min. In similar transfection experiments, secreted apoE Leiden was significantly less glycosylated than normal apoE3 (21.7% vs. 36.6%, P < 0.005, n = 4), a finding also noted for apoE Leiden in human plasma. In in vitro incubation experiments, apoE Leiden showed a markedly higher preference for VLDL of normolipidemic human plasma when compared to both apoE3 (2.6-fold, P < 0.001) and apoE4 (1.6-fold, P < 0.001). These results suggest that the accumulation of apoE Leiden in VLDL derives from a high affinity of the mutant protein for the VLDL. This enrichment in defective apoE probably exacerbates impairment of VLDL removal from the circulation, thus contributing to the dominant transmission of type III hyperlipoproteinemia. PMID- 8468529 TI - Hepatic lipase treatment of chylomicron remnants increases exposure of apolipoprotein E. AB - The consequences of hepatic lipase treatment of chylomicron remnants were studied. Rats were fed corn oil to induce production and secretion of chylomicrons and were then injected with polyclonal antiserum raised against hepatic lipase to specifically and quantitatively inhibit hepatic lipase activity in vivo. A fraction enriched in chylomicron remnants was isolated from rat plasma by a brief centrifugation step that preferentially isolates triglyceride-rich apolipoprotein (apo) B-48-containing lipoproteins. The chylomicron remnants were then treated with hepatic lipase in vitro, or incubated under identical conditions in the absence of enzyme (control incubations). Hepatic lipase-treated and control chylomicron remnants were isolated by a second brief centrifugation step using discontinuous salt gradients. Control lipoproteins were collected from one discrete band at d < 1.02 g/ml. Hepatic lipase-treated chylomicron remnants formed two discrete bands and were collected at two densities: d < 1.02 g/ml and 1.02 < d < 1.04 g/ml. The buoyant (d < 1.02 g/ml) subfraction of hepatic lipase treated chylomicron remnants was depleted of 62% of the total phospholipid when compared to control d < 1.02 g/ml lipoproteins. The dense (1.02 < d < 1.04 g/ml) subfraction of hepatic lipase-treated chylomicron remnants was depleted of 65% of particle phospholipid content and 90% of particle triglyceride content when compared to control d < 1.02 g/ml lipoproteins. The dense (1.02 < d < 1.04 g/ml) subfraction of hepatic lipase-treated chylomicron remnants showed 5- to 7-fold greater immunoreactivity of apoE when compared to control lipoproteins in competitive displacement immunoassays. These data suggest that extensive hydrolysis of chylomicron remnant phospholipid and triglyceride leads to the formation of a dense remnant particle that contains highly exposed apoE. This increased exposure of apoE may be the key to the previously observed increased degradation of chylomicron remnants treated with hepatic lipase because more exposed apoE may bind better to cell surface lipoprotein receptors. Furthermore, the data imply that hepatic lipase cleaves chylomicron remnant phospholipid and triglyceride in a sequential fashion; hydrolytic intermediates depleted only of phospholipid precede the formation of a smaller dense remnant particle depleted of phospholipid and triglyceride. PMID- 8468530 TI - Exclusive localization in peroxisomes of dihydroxyacetone phosphate acyltransferase and alkyl-dihydroxyacetone phosphate synthase in rat liver. AB - Dihydroxyacetone phosphate acyl transferase (DHAP-AT), alkyl dihydroxyacetone phosphate synthase (alkyl-DHAP-synthase), and glycerol-3-phosphate acyltransferase (GPAT) activities were investigated under optimal assay conditions using highly purified organelle preparations. The data presented clearly indicate that GPAT activity was mainly localized in mitochondria and microsomes, whereas DHAP-AT and alkyl-DHAP-synthase activities were exclusively localized in peroxisomes. A small fraction of the total DHAP-AT and alkyl-DHAP synthase activities observed in purified mitochondrial preparations was due to the presence of intact peroxisomes. DHAP-AT and alkyl-DHAP-synthase activities were very low in purified microsomes (< 1% compared to peroxisomes) and these activities are thought to be due to sedimentation of peroxisomal fragments (generated during homogenization of liver and processing of liver homogenate) with microsomes. The results indicate that the dihydroxyacetone phosphate pathway does not contribute to the synthesis of glycerolipids other than ether lipids in rat liver. The ether bond formation occurs exclusively in peroxisomes, and all the biosynthetic reactions for plasmalogen synthesis may also be operating within peroxisomes in rat liver. PMID- 8468531 TI - Lethal damage to endothelial cells by oxidized low density lipoprotein: role of selenoperoxidases in cytoprotection against lipid hydroperoxide- and iron mediated reactions. AB - Oxidized low density lipoprotein (LDLox) is believed to be an important contributor to endothelial cytodamage and atherogenesis. The purpose of this study was to examine the role of glutathione (GSH) and GSH-dependent selenoperoxidases in cytoprotection against the damaging effects of LDLox. When irradiated in the presence of a phthalocyanine sensitizing dye, human LDL accumulated chromatographically detectable and iodometrically measurable lipid hydroperoxides (LOOHs). Photogenerated LDLox caused lethal damage to bovine aortic endothelial (BAE) cells in vitro, as determined by lactate dehydrogenase release and inhibition of thiazolyl blue reduction. When depleted of GSH by buthionine sulfoximine treatment, BAE cells became more sensitive to LDLox. Cells grown in 2% serum/DME-HAM's F-12 medium without added selenium [Se(-) cells] exhibited far lower GSH-peroxidase and phospholipid hydroperoxide GSH-peroxidase activities than selenium-supplemented controls [Se(+) cells], and were much more sensitive to oxidative injury induced by t-butyl hydroperoxide, liposomal cholesterol hydroperoxides, and LDLox. Preincubation of LDLox with GSH and Ebselen (a selenoperoxidase mimetic) resulted in a dramatic reduction in both LOOH content and cytotoxicity. Moreover, treating Se(-) cells themselves with Ebselen substantially restored their resistance to LDLox-induced damage. LDLox toxicity to Se(-) cells was strongly inhibited by desferrioxamine and stimulated by ferric-8-hydroxyquinoline (a lipophilic chelate), indicating that iron is an active participant in oxidative damage. These results demonstrate that the GSH dependent selenoperoxidase(s) play(s) an important role in cellular defense against oxidized low density lipoprotein, presumably by detoxifying lipid hydroperoxides and thereby preventing their iron-catalyzed decomposition to damaging free radical intermediates. PMID- 8468532 TI - Unique lipids of primate spermatozoa: desmosterol and docosahexaenoic acid. AB - Spermatozoa represent a tissue readily accessible for study after various exogenous perturbations. To characterize the lipid composition of monkey sperm and to establish a baseline from which dietary or pharmaceutical influences may then be evaluated, we collected semen samples from five rhesus monkeys by electroejaculation and analyzed the sperm for sterols, fatty acid composition, and the molecular species of the ethanolamine glycerophospholipids. Two sterols were identified: cholesterol, 41%, and desmosterol, 59% of total sterols. Desmosterol was found only in the free form. Cholesterol existed in three different forms: free, 60%; esterified, 20%; and sulfated, 20%. Docosahexaenoic acid (22:6, DHA) was almost the only n-3 fatty acid in sperm phospholipids, 24% of the total fatty acids. DHA was present mainly in phosphatidylcholine and phosphatidylethanolamine. Oleic and palmitic acids were the predominant monounsaturated and saturated fatty acids. The ethanolamine glycerophospholipids were separated into three subclasses: diacyl 49%, alkenylacyl 43%, and alkylacyl 8%. Thirteen molecular species were identified and quantified. The sn-1 position of these molecular species contained exclusively 16:0, 18:0, or 18:1. The sn-2 position contained n-3, n-6, and n-9, as well as saturated fatty acids. The molecular species having n-3 fatty acids in the sn-2 position contributed 43, 73, and 100% of the total in the diacyl, alkenylacyl, and alkylacyl subclasses, respectively. The presence of the unusual sterol, desmosterol, a cholesterol precursor not found in measurable quantities in any other tissue suggests an important functional and structural role for desmosterol in spermatozoa. The other unique lipids, cholesterol sulfate and the n-3 docosahexaenoic acid, may also have a significant role in the function of spermatozoa. PMID- 8468533 TI - Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length. AB - Familial hypobetalipoproteinemia can be caused by mutations in the apolipoprotein (apo)B gene that interfere with the translation of a full-length apoB molecule. Frequently, a truncated apoB molecule can be detected in the plasma lipoproteins of affected subjects. In this report, we characterize four different apoB gene mutations causing hypobetalipoproteinemia that are associated with the synthesis of truncated apoB proteins. Two of the mutations are nonsense mutations caused by single nucleotide substitutions; these mutations are associated with the production of apoB-32.5 (1473 amino acids) and apoB-82 (3733 amino acids). The other two mutations are single nucleotide deletions (of apoB cDNA nucleotides 7295 and 7359, respectively). The altered reading frames created by these different frameshift mutations terminated with the same stop codon, and both therefore yielded a truncated protein of identical size: apoB-52.8 (2395 amino acids). The two apoB-52.8 proteins differ, however, in the number of novel carboxyl-terminal amino acids introduced by the frameshift. The buoyant density of lipoproteins containing the truncated apoBs was inversely related to the length of the truncated apoB. ApoB-32.5 was present only in high density lipoproteins (HDL) and the d > 1.21 g/ml fraction, whereas apoB-82 was present almost exclusively in very low density lipoproteins (VLDL). ApoB-52.8 was present primarily in VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL); trace amounts were observed in the HDL. PMID- 8468534 TI - Intracellular maturation of apolipoprotein[a] and assembly of lipoprotein[a] in primary baboon hepatocytes. AB - The glycoprotein apolipoprotein[a] (apo[a]) is present in plasma at highly variable concentrations and appears as a number of genetically determined size isoforms (400-800 kDa), disulfide linked to apoB-100 in low density lipoprotein to produce lipoprotein [a](Lp[a]). Apo[a] is synthesized by the liver, but the site of association of apo[a] and apoB and factors that regulate its production are unknown. To examine the morphogenesis of the Lp[a] particle, baboon hepatocytes expressing a single, low molecular weight isoform of apo[a] were labeled with [35S]cysteine and methionine, and apo[a] was analyzed by immunoprecipitation and SDS-PAGE. Steady-state labeling revealed two molecular weight forms of apo[a] inside the cell. Only the large form was recovered from the culture medium. Pulse-chase studies and endoglycosidase treatment revealed that the lower molecular weight form of apo[a] represented a precursor with a prolonged residence time in the endoplasmic reticulum or an early Golgi compartment, after which it was processed to the mature form. A proportion of the mature form of apo[a] was rapidly secreted after synthesis, whereas the remainder had a prolonged residence time in a late Golgi compartment. In all experiments, apoB co-precipitated with apo[a] from the culture medium, but not from cell lysates. Density gradient ultracentrifugation and immunoblot analysis revealed that the majority of apo[a] was secreted into the medium in a free form, suggesting that the association between apo[a] and apoB occurred after secretion. Regulation of the movement of apo[a] between intracellular compartments may be one mechanism by which the plasma levels of Lp[a] are influenced. PMID- 8468535 TI - Half-sib mating structures. AB - All ways in which all matings in a population can be between half-sibs under a generalization of regular systems of inbreeding are characterized for both finite and infinite populations. A model of random half-sib mating is developed and analyzed, and the asymptotic configuration of populations subject to it is described. The classical model of half-sib mating which ensues from the standard definition of regular systems of inbreeding is only one of many ways a population can propagate by half-sib mating, and a wide range of genetic identity is possible dependent on which half-sib mating structure governs a population. PMID- 8468536 TI - Entropy and convergence in dynamics and demography. AB - Demographic dynamics is formally equivalent to the dynamics of a Markov chain, as is true of some nonlinear dynamical systems. Convergence to demographic equilibrium can be studied in terms of convergence in the Markov chain. Tuljapurkar (1982) showed that population entropy (Kolmogorov-Sinai entropy) provides information on the rate of this convergence. This paper begins by considering finite state Markov chains, providing elementary proofs of the relationship between convergence rate and entropy, and discusses in detail the uses and limitations of entropy as a convergence measure; these results also apply to Markovian dynamical systems. Next, new qualitative and quantitative arguments are used to discuss the demographic meaning of entropy. An exact relationship is established giving population entropy in terms of the eigenvalues of the Leslie matrix characteristic equation. Finally, the significance of imprimitive and periodic limits is discussed in relation to population entropy. PMID- 8468537 TI - A parameter identification problem arising from a model of canalicular bile formation. AB - We develop a simple mathematical model for bile formation and analyze some features of the model that suggest the design for future physiological experiments. The mathematical model results in a boundary value problem for a system of functional differential equations depending on several physical parameters. From the observability of the boundary values we can identify, both qualitatively and quantitatively, some of these physical parameters. This identification then suggests physical experiments from which one could infer some of the bile transport phenomena that are not, at present, directly observable. The mathematical parameter identification problem is solved by converting the boundary value problem to a transition time problem for a quadratic system of ordinary differential equations on the plane where we are able to employ some special properties of quadratic systems in order to obtain a solution. PMID- 8468538 TI - DNA damage in non-proliferating cells subjected to ionizing irradiation at high or low dose rates. AB - Ionizing radiation damage to the genome of a non-cycling mammalian cell is analyzed using continuous time Markov chains. Immediate damage induced by the radiation is modeled as a batch Poisson arrival process of DNA double strand breaks (DSBs). Different kinds of radiation, for example gamma rays or alpha particles, have different batch probabilities. Enzymatic modulation of the immediate damage is modeled as a Markov process similar to the processes described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete exchange model, which postulates that radiation induced DSBs can subsequently either undergo enzymatically mediated repair (restitution) or can participate pairwise in chromosome exchanges, some of which make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. A complete solution of the Markov chain is known for the case that the exchange rate constant is negligible so that no irremediable chromosome lesions are produced and DSBs are the only damage to the genome. Using PDEs for generating functions, a perturbation calculation is made assuming the exchange rate constant is small compared to the repair rate constant. Some non-perturbative results applicable to very prolonged irradiation are also obtained using matrix methods: Perron-Frobenius theory, variational methods and numerical approximations of eigenvalues. Applications to experimental results on expected values, variances and statistical distributions of DNA lesions are briefly outlined. Continuous time Markov chain models are the most systematic of those current radiation damage models which treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g. ignore diffusion limitations). They contain most other homogeneous models as special cases, limiting cases or approximations. However, applying the continuous time Markov chain models to studying spatial dependence of DSB interactions, which is generally believed to be very important in some situations, presents difficulties. PMID- 8468539 TI - Control of intrinsic buccal muscles by motoneurons B11, B15, and B16 in Aplysia californica. AB - To further define the control of intrinsic buccal muscles by identified motoneurons B11, B15, and B16 in Aplysia californica, we made physiological recordings from semi-intact and isolated preparations of the buccal ganglia and buccal mass. B15 and B16 were previously known to innervate muscle 15 (also called the accessory radula closer muscle). We show here that these motoneurons also innervate other buccal muscles ipsilateral to their cell bodies; for example, B15 reliably innervates and can cause contraction in intrinsic muscle I4. Likewise, B11 appears to innervate all of the intrinsic buccal muscles, but elicits contractions only in I4. The form and time course of synaptic plasticity displayed by these motoneurons is common to all the muscles they innervate. No evidence for electrical coupling between fibers of adjacent muscles could be obtained, suggesting that all recorded innervation is direct. Like B15 and B16 (Cohen et al., '78), B11 neuromuscular synapses appear to be cholinergic, since they are reversibly antagonized by hexamethonium and d-tubocurarine (acetylcholine [ACh] receptor antagonists). In addition, direct application of ACh elicits depolarizing responses and contractions in I4 which are also blocked by hexamethonium. Application of glutamate and GABA do not elicit depolarizations or contractions in I4 or I5. We conclude that these motoneurons control radula position through complex synaptic actions on multiple intrinsic buccal muscles, using ACh as their conventional transmitter. PMID- 8468540 TI - Prolactin and interrenal hormone balance in adult specimens of Xenopus laevis exposed to hyperosmotic stress for up to one week. AB - Adult female specimens of Xenopus laevis were exposed to diluted artificial seawater for up to 1 week. Statistically significant increases were observed in serum levels of aldosterone and corticosterone, concomitant with a drop in levels of prolactin (PRL) receptors in the cell membranes of the epidermis and kidney, which can be taken as an indicator of the levels of circulating PRL. The changes in hormone levels were detected after 1 day, being followed by a gradual restoration of the initial mean levels of these hormones when the exposure to hyperosmotic stress was extended for up to 2 or 7 days. Comparison of the above results with those previously obtained in Xenopus after longer exposure (15 days) to brackish water substantiates the necessity of recording possible initial fluctuations, as well as any changes that occur over the course of longer exposure during which time adaptation to environmental changes are likely to take place. The reverse responses, which may be not independent of one another, in terms of levels of corticoids and PRL in the animals exposed to hyperosmotic stress, are discussed. A survey of the literature suggests that, in Xenopus, as in the case of other less strictly water-dwelling amphibians, PRL is one of the hormones required for life in fresh water. PMID- 8468541 TI - Stage-related production of 21-hydroxylated progestins by the dogfish (Squalus acanthias) testis. AB - Using shark (Squalus acanthias) testicular microsomes and [3H]progesterone ([3H]P) and [3H]17 alpha-hydroxyprogesterone ([3H]17 alpha-P) as substrates, two major products of 21-hydroxylase action were identified; respectively, 21-hydroxy 4-pregnen-3-one (11-deoxycorticosterone, DOC) and 17 alpha,21-dihydroxy-4-pregnen 3-one (11-deoxycortisol,S). Additional products of 17 alpha-hydroxylase/C-17,20 lyase action were detected: 17 alpha-hydroxyprogesterone (17 alpha P), testosterone (T), and androstenedione (AE). When microsomes derived from tissues in premeiotic (PrM), meiotic (M), and postmeiotic (PoM) stages of spermatogenesis were compared, maturation-related increases were observed with both 21 hydroxylase (3- to 20-fold) and 17 alpha-hydroxylase (2- to 6-fold). With [3H]P as tracer, the half-maximal substrate concentrations (Km = 0.2-1.0 microM) and maximal reaction velocities (Vmax = 9-25 pmol/mg protein/min) were similar for both enzymes when assayed in the same preparation, suggesting they compete for available substrate. Also, the presence of 1- or 10-fold molar excess radioinert DOC reduced conversion of [3H]P to 17 alpha-hydroxylated products. [3H]DOC itself was a substrate of 17 alpha-hydroxylation but not C-17,20-lyase action. Expression of 21-hydroxylase and 17 alpha-hydroxylase activities in cultured spermatocysts (intact germ cell/Sertoli cell units) was confirmed by detection of immunoreactive 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S),S,17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-P), DOC, P and T in spent media. 20 beta-S and S secretion increased and 17 alpha,20 beta-P decreased progressively with stage of maturation, but DOC was similar in all stages. P secretion was maximal and T lowest in M-stage spermatocysts, but when DOC (0.1 microM) was added to PrM or PoM spermatocysts, T output decreased. Taken together, the data suggest that 21-hydroxylating pathways, via direct and indirect mechanisms, affect accumulation of bioactive steroids (P and T) differentially by stage of spermatogenic development. Whether 21-hydroxylated progestins produced in shark testis have paracrine or endocrine actions in their own right remains to be investigated. PMID- 8468542 TI - Basal, diurnal, and stress-induced levels of glucose and glucocorticoids in captive bats. AB - Plasma levels of glucocorticoids and glucose were measured in three species of fruit bats (Chiroptera) sampled from captive populations. Three species of Old World bats (Pteropus vampyrus, P. Hypomelanus, and Rousettus aegyptiacus) had plasma levels of glucose that were within the normal mammalian range (80-100 mg/dl), with no difference between males and females. All animals had detectable levels of one or both of the major glucocorticoids (cortisol and corticosterone) found in mammals. Steroid levels were highest in P. hypomelanus (cortisol: 1,269 +/- 207 ng/ml; corticosterone; 590 +/- 154 ng/ml) and lowest in R. aegyptiacus (corticosterone: 36 +/- 4 ng/ml; cortisol not determined). Diurnal changes in these steroids and the effects of handling and restraint stress were further investigated in P. hypomelanus. Experimental animals were captured in their roost quarters, bled once by venupuncture within 3 min, placed singly into a small holding chamber for 50-60 min, and bled again. This procedure was performed at four different times over the course of 24 h with different groups of animals. Glucose was at a minimum just before and a maximum just after the period of food presentation. Cortisol levels remained relatively constant throughout the day roosting period and significantly declined to their lowest level in the period following food presentation. As expected, the effects of handling and isolation caused a significant increase in both plasma cortisol and glucose levels. When individual P. hypomelanus were subjected to 3 h restraint stress in small plastic wire-mesh restraining devices, cortisol levels rose approximately 800% by 2 h, with the first significant increase at 20 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468543 TI - Eggshell formation in Bdelloura candida, an ectoparasitic turbellarian of the horseshoe crab Limulus polyphemus. AB - The marine triclad Bdelloura candida (Turbellaria) episodically deposits stalked eggshells onto the gill lamellae of the horseshoe crab Limulus polyphemus. Ultrastructural and biochemical analyses indicate that the eggshells consist of primary inner and secondary outer layers. Protein of the primary layer is rich in glycine, aspartate/asparagine, serine, and 3,4-dihydroxyphenylalanine (Dopa). In this regard it resembles the eggshell compositions of other members of the phylum Platyhelminthes. The primary layer appears to be derived from precursors produced in the vitelline cells of the flatworm. Each egg-laying episode consumes all of the precursor-containing vitelline cells. A Dopa-containing protein, vitelline protein 1 (Vp1), has been isolated from B. candida and resembles the primary eggshell layer in its composition. Vp1 has an apparent molecular weight of 34.4 and an acidic pI. Dopa-containing proteins are presumed to be directly involved in the cross-linking reactions that accompany quinone-tanning. The secondary outer layer of the eggshell may serve to adhere the eggshell to the gill. Its amino acid composition is unlike that of the primary eggshell and nothing is known about its precursors. PMID- 8468544 TI - Pheromonal regulation of the mouse estrous cycle by a heterogenotypic male. AB - The role of male pheromones in estrous cyclicity was studied in mice selected for different reproductive traits. When females are exposed to males of their own strain, estrous cycles are highly regular in females selected for increased embryo survival (line E). In contrast, cycle regularity is reduced by exposure of line E females to males from a strain characterized by irregular estrous cycles (line CN-). To investigate the inhibition of estrous cyclicity and the role of androgen in this phenomenon, line E females were housed in the olfactory presence of E males and later rehoused with one of the following: intact or castrated males of line E (homogenotypic condition) or line CN-heterogenotypic condition) or castrated CN- males provided with testosterone replacement. A final exposure to homogenotypic (line E) males was provided. Estrous cyclicity was decreased when line E females were rehoused with intact or castrated CN- males. Metestrus was prolonged by intact CN- males, whereas diestrus was prolonged in the presence of castrated CN- males. Androgen treatment did not enable castrated CN- males to prolong metestrus. These results demonstrate that: 1) heterogenotypic pheromones inhibit estrous cyclicity in line E; and 2) the inhibitory influence of line CN- males on line E estrous cyclicity is mediated by factors in addition to or other than testosterone. PMID- 8468545 TI - Spawning in the zebra mussel (Dreissena polymorpha): activation by internal or external application of serotonin. AB - The zebra mussel, Dreissena polymorpha, was recently introduced accidentally into the Great Lakes and, due in part to its prodigious reproductive capacity, is spreading rapidly in temperate fresh waters of North America. The present studies examine some of the mechanisms that regulate spawning in this animal. In August and September 1990 and in May 1991 injection of serotonin (5-hydroxytryptamine, 5 HT) induced ripe male, but not female, zebra mussels to spawn. During mid-summer 1991, 5-HT induced spawning in both males and females, and 5-HT could produce spawning responses by either injection or external application. External pH over a broad range (6.0 to 9.1) had no effect on spawning, neither inhibiting induction of spawning by 5-HT nor significantly eliciting spawning itself. With external application, 10(-3) M and 10(-4) M 5-HT caused spawning, but 10(-5) M and 10(-6) M did not. Cyproheptadine, a 5-HT receptor antagonist, reduced the response of both males and females by more than half. Spawning in response to 5 HT was blocked at 4 degrees C, but not at 12 degrees C, 20 degrees C, or 27 degrees C. For male zebra mussels morphological criteria for judging gonadal maturity were well-correlated with probability of spawning in response to 5-HT. For females, the likelihood of spawning in response to 5-HT was not tightly coupled to morphological maturity of the gonad, with many morphologically ripe females failing to spawn and some apparently immature animals releasing oocytes. Prior spawning reduced subsequent responsiveness and intensity of spawning of animals to 5-HT. These experiments support a role for 5-HT in regulating reproduction in zebra mussels and help define conditions by which zebra mussel spawning may be stimulated or inhibited. PMID- 8468546 TI - Similar responses to pharmacological agents of 1,2-OAG-induced compaction-like adhesion of two-cell mouse embryo to physiological compaction. AB - A comparison was made of responses to pharmacological agents between cell adhesion induced by an activator of Ca(2+)-phospholipid-dependent protein kinase (PKC) and physiological compaction in mouse embryos. An activator of PKC, 1 oleoyl-2-acetyl-sn-glycerol (1,2-OAG) induced the compaction-like adhesion of cells in two-cell embryos within 5-10 min and the adhesion lasted during the course of treatment for 1 h. W-7 and W-5 (calmodulin antagonists) and cytochalasin B and cytochalasin D (inhibitors of the polymerization of microfilaments) each completely interfered with the 1,2-OAG-induced adhesion of cells. Two-cell embryos having once shown evidence of cell adhesion in response to 1,2-OAG were decompacted when they were transferred to a medium that contained 1,2-OAG and any one of the agents described above. Colchicine and colcemid (inhibitors of the polymerization of microtubules) and tunicamycin (an inhibitor of N-linked protein glycosylation) each had no effect on the 1,2-OAG-induced adhesion of cells. In Ca(2+)-free medium, treatment with 1,2-OAG failed to induce any cell adhesion. These results are very similar to those reported for physiological compaction at the late eight-cell stage. Thus, the compaction-like adhesion of cells in mouse embryos at the two-cell stage appears to be a calmodulin-dependent process, requiring assembled microfilaments and extracellular Ca2+ ions but not microtubules or N-linked glycoproteins as is the case for the physiological compaction. PMID- 8468547 TI - Nightly increase in visual sensitivity correlated with bioluminescent flashing activity in the firefly Photuris versicolor (Coleoptera:Lampyridae). AB - Changes in visual sensitivity as a function of time-of-day were studied in the firefly Photuris versicolor. The electroretinograms (ERGs) elicited by photic stimuli of constant intensity and duration were recorded over long periods (18-52 h) while the insect was in constant darkness. The amplitudes of the ERGs elicited by the standard flash were small and remained constant during the daytime hours and increased on average sixfold during the evening hours, reaching a maximum at the onset of darkness and remaining at that high level until the morning hours. The amplitude of the standard response again was reduced in the morning hours to a daytime low value which again persisted until the following evening (Fig. 1). In addition, a series of flashes of varying intensity were administered periodically and logV/logI curves as a function of time-of-day were obtained. Compared to the daytime logV/logI curves, the nighttime curves were shifted about 4 log units towards the left on the intensity axis (Fig. 2). This period of high visual sensitivity was correlated with the species' flashing activity period, which occurs during the night hours (Fig. 1). PMID- 8468548 TI - Maize stripe virus RNA5 is of negative polarity and encodes a highly basic protein. AB - The entire 1317 nucleotide sequence of the maize stripe virus (MStV) RNA5 was determined. Only one open reading frame (ORF) was identified and was found in the viral complementary RNA (vcRNA). This ORF appears to encode a protein of M(r) 44237, hereafter referred to as NS5 delta. In vitro translation of transcripts representing nearly full-length RNA5 vcRNA yielded products of the predicted size, as well as some smaller, less prominent products. No products were identified from transcripts of viral polarity. RNA hybridization analyses of MStV infected Zea mays revealed RNAs corresponding only to full-length RNA5, but both positive and negative polarity RNAs were abundant. Analysis of the NS5 amino acid sequence revealed that it is extremely basic, containing 21% arginine and lysine. Database comparisons showed that NS5 had no significant similarity to other protein sequences. PMID- 8468549 TI - Sequence analysis of the parsnip yellow fleck virus polyprotein: evidence of affinities with picornaviruses. AB - The 9.9 kb monopartite ssRNA genome of parsnip yellow fleck virus (PYFV) encodes a polyprotein from which the functional proteins are assumed to arise by proteolytic cleavage. The 22.5K, 26K and 31K particle proteins were mapped in the polyprotein by determining their N-terminal amino acid sequences, and were found to begin at amino acid positions 395, 589 and 811, respectively. There could be polypeptide(s) of up to 43K on the N-terminal side of the particle protein sequences. A region within the 26K particle protein has sequence similarity to the VP3 particle protein of picornaviruses. Three other regions in the PYFV polyprotein have sequence similarity to regions thought to have RNA polymerase, NTP-binding and protease functions in the polyproteins of picornaviruses, comoviruses and nepoviruses. Despite these similarities in sequence and in genome organization to viruses in the picorna-like supergroup, PYFV is distinct from all other plant and animal viruses described. This justifies placing it in a separate plant virus genus for which the name 'sequivirus' has been proposed. PMID- 8468550 TI - Functional domains of the p10 protein of Autographa californica nuclear polyhedrosis virus. AB - Distinct functional domains in the Autographa californica nuclear polyhedrosis virus p10 protein were identified by analysis of p10 mutants. When up to 15 amino acids from the carboxy terminus were deleted, truncated p10 proteins were found in both the nucleus and the cytoplasm of infected cells, but formed no fibrillar structures. This suggested that the positively charged carboxy terminus is not required for nuclear or cytoplasmic localization of p10 protein, but is involved in protein-protein interactions leading to assembly of the p10 protein into fibrillar structures. Absence of the p10 protein prevented the release of polyhedra from infected cells, caused by impaired nuclear disintegration. This function of the p10 protein appears to be located between amino acid residues 52 and 79. The amino-terminal half of the p10 protein has already been implicated in the self-aggregation of this protein. Thus fibrillar structure formation, nuclear disintegration and intermolecular p10 protein interactions seem to be three separate functions of the p10 protein and these functions are located in distinct domains of the protein. The mutants expressing truncated p10 proteins were impaired in electron-dense spacer formation but polyhedron envelopes were still formed. This result suggested that the formation of electron-dense spacers is not a prerequisite for the formation of polyhedron envelopes. PMID- 8468551 TI - Selective effects on adenovirus late gene expression of deleting the E1b 55K protein. AB - The E1b gene of human adenovirus 5 (Ad5) encodes a 55K product previously shown to be required for the efficient accumulation of mRNAs derived from the major late primary transcript in the cytoplasm of infected cells. This finding is extended here to include the transcripts from other viral promoters activated during the late phase of infection. Conversely, accumulation of mRNA derived from the major late promoter at early times is not dependent on this E1b function. Cytoplasmic levels of the various differentially spliced products of the major late unit are not equally dependent on the E1b 55K protein. Rather, the longest mRNA species within each 3'-coterminal family shows the greatest dependence. These findings support a model in which the Ad5 E1b 55K protein acts to facilitate the movement of mature viral mRNA away from the nuclear matrix of the infected cell. PMID- 8468552 TI - Role of phosphorylation near the amino terminus of adenovirus type 5 early region 1A proteins. AB - Human adenovirus early region 1A (E1A) proteins act as transcriptional regulators and function in the control of DNA synthesis and cell transformation. Little is known about how these viral products are functionally regulated. E1A proteins of adenovirus serotype 5 (Ad5) are phosphorylated at several serine residues and previous studies had indicated that both Ser-89 and Ser-219 are substrates for one or more of the cdc2 family of cell cycle kinases. A second residue near the amino terminus, Ser-96, may also be a site. Although phosphorylation of Ser-89 causes a major shift in gel mobility, the effect on E1A biological activity is unclear. In the present studies we have shown by mutational analysis that phosphorylation at Ser-89 also regulates phosphorylation at Ser-96, suggesting that the gel mobility shift is the result of multiple phosphorylation events. Phosphorylation at Ser-89 did not seem to affect E1A-mediated repression of the simian virus 40 enhancer or trans-activation of the E3 promoter significantly, but it did appear to have a modest but significant effect on transformation of primary baby rat kidney cells. PMID- 8468553 TI - Molecular cloning and expression in Escherichia coli of the glycoprotein gene of VHS virus, and immunization of rainbow trout with the recombinant protein. AB - The gene encoding the envelope glycoprotein of a recent Danish isolate of a salmonid rhabdovirus, viral haemorrhagic septicaemia virus (VHSV) has been cloned and sequenced at the cDNA level. When compared with the deduced sequence of a French isolate of VHSV, it was noted that there were 13 amino acid substitutions in the Danish virus. Amino acid homologies with the glycoprotein of a North American salmonid rhabdovirus (infectious haematopoietic necrosis virus) indicate a high degree of structural similarity between the two fish rhabdovirus glycoproteins. Results from partial enzymatic deglycosylation of the viral protein indicate that all four NXT/S sites found in the sequence are N glycosylated in the virus. The glycoprotein, without the N-terminal leader sequence and C-terminal hydrophobic anchor segment, was expressed in Escherichia coli as a factor Xa protease-cleavable fusion protein. The purified and renatured viral part of the recombinant protein was able to elicit VHSV-specific antibodies and neutralizing antibody activity in serum when injected into rainbow trout. PMID- 8468554 TI - Characterization of morbilliviruses isolated from dolphins and porpoises in Europe. AB - A previously unidentified morbillivirus was isolated from two harbour porpoises (Phocoena phocoena) that had died in the Dutch Waddensea (North Sea) in 1990. This porpoise morbillivirus (PMV) and a dolphin morbillivirus (DMV), which had recently caused a heavy mortality in Mediterranean striped dolphins (Stenella coeruleoalba), were compared antigenically with other members of the genus Morbillivirus, including the newly recognized phocine distemper virus type 1. DMV and PMV proved to be similar but distinct morbillivurses, closely related to rinderpest virus and peste-des-petitsruminants virus. Cell cultures of cetacean, pinniped, ruminant and canine origin showed a different pattern of susceptibility to DMV and PMV infection. Ruminants and dogs proved to be susceptible to experimental infection with DMV and PMV, which both caused a transient leukopenia most pronounced in the ruminants. Pre-exposure of dogs to DMV and PMV protected them from developing CDV viraemia and clinical signs upon challenge infection with virulent CDV. A serological survey among stranded animals of different cetacean species in Europe indicated that infections with DMV- and PMV-like morbilliviruses are not uncommon among these aquatic mammals. PMID- 8468555 TI - The role of gp55 N-glycosylation in pathogenesis of Friend spleen focus-forming virus. AB - The product of the envelope gene (gp55) of Friend spleen focus-forming virus is responsible for the acute form of erythroleukaemia caused by this virus. In order to investigate the role that the four known N-linked carbohydrate side-chains of gp55 play in pathogenesis, we have inactivated the four N-glycosylation signals by mutating the asparagine residues of these four sites into serine. When glycosylation sites 1 and/or 2 were altered, the viruses remained fully pathogenic. However, mutation at either of glycosylation sites 3 or 4 rendered the virus apathogenic, independent of mutations at other sites. Furthermore, when site 3 was changed, a new product appeared which seemed to have acquired a carbohydrate chain at a position normally not glycosylated, presumably at position Asn378. PMID- 8468556 TI - Mutational analysis of Moloney murine leukaemia virus surface protein gp70. AB - Ten mutations were generated in the env gene of Moloney murine leukaemia virus DNA. The mutations were made by site-directed mutagenesis to alter basic amino acids (lysine or arginine) in the surface glycoprotein gp70. Mutants were investigated following transfection into NIH/3T3 cells. All 10 mutants released virion particles into the medium, suggesting that none of the mutations affected overall viral gene expression or virion budding. Two mutants were positive in XC plaque assay, reverse transcriptase assay and re-infection experiments, showing that these mutations occurred in parts of the molecule not essential for infection. Three mutants were negative in both the XC plaque assay and re infection experiments, suggesting that they make non-infectious virus particles. The results indicate a defect in the early phase of infection, perhaps in receptor binding or in the fusion of virion and host membranes. The other mutations resulted in reduced infectivity of released virion particles. PMID- 8468557 TI - In vitro non-productive infection of purified natural killer cells by the BRU isolate of the human immunodeficiency virus type 1. AB - Highly purified natural killer (NK) cell lines and clones, displaying the typical phenotype, morphology and function and obtained from healthy blood donors, were infected in vitro with the BRU isolate of human immunodeficiency virus type 1 (HIV-1). There was no significant increase in reverse transcriptase activity and levels of p24 antigen in the supernatants, but positive staining was observed using an immunogold technique with polyclonal anti-HIV-1 antibodies. When infected NK cells were co-cultivated with autologous non-infected CD4+ mitogen activated cells, significant levels of reverse transcriptase activity and p24 antigen in supernatants were detected. Giant syncytial cells and a high number of mature virion particles were also evident. When NK cell lines or clones from HIV 1-infected patients were studied, neither the presence of p24 antigen nor reverse transcriptase activity was detected in the supernatants after stimulation with mitogens, cytokines or co-culture with allogeneic CD4+ mitogen-activated cells. PCR studies did not detect HIV-1 genes in freshly purified NK cells, cell lines or clones from infected patients. Taken together these results suggest that (i) normal NK cells can be infected in vitro by the HIV-1 BRU isolate in a non productive fashion, (ii) PCR with NK cell DNA of HIV-1-infected patients indicates that in vivo few of these cells, if any, are infected by HIV-1 and (iii) the mechanisms responsible for the impairment of NK cell function during HIV-1 infection remain to be determined and are probably not related to a direct cytopathic effect of the virus. PMID- 8468558 TI - Class I major histocompatibility complex-restricted cytotoxic T cell responses to vaccinia virus in humans. AB - Cytotoxic T lymphocyte (CTL) responses to vaccinia virus (VV) were studied in human subjects receiving smallpox vaccine by dermal scarification. After in vitro restimulation with VV, peripheral blood mononuclear cells (PBMCs) from three of six vaccinated subjects killed virus-infected target cells. VV-specific, HLA restricted CTL activity was mediated primarily by CD8+ cells, although low levels of lytic activity by CD4+ cells were observed in some experiments. Two of the three responders had no history of exposure to VV prior to vaccination, whereas all three non-responders were vaccinated against smallpox during childhood. PBMCs from an additional three subjects who had received smallpox vaccine at least 20 years previously were negative for CTL activity. These data suggest that the duration of memory CTL populations against VV in the peripheral blood is limited, and that pre-existing immunity to VV may interfere with boosting of the CTL response upon revaccination. PMID- 8468559 TI - Nucleotide sequence and possible ambisense coding strategy of rice stripe virus RNA segment 2. AB - The complete nucleotide sequence (3514 nucleotides) of RNA segment 2 of rice stripe virus (RSV), the prototype member of tenuivirus group, was determined. In the virus-sense RNA an open reading frame (ORF) is present which encodes a 199 amino acid protein of M(r) 22,762. Another long ORF encoding an 834 amino acid protein with M(r) 94,047 (94K) exists in the virus-complementary RNA. Between these two ORFs, there is a long non-coding intergenic region of 299 nucleotides. The sequence suggests that RNA 2 has an ambisense coding strategy as found for RSV RNAs 3 and 4. The putative 94K protein carries stretches with an amino acid sequence showing weak similarity to parts of the membrane glycoproteins of Punta Toro and Uukuniemi phleboviruses of the family Bunyaviridae, suggesting a possible distinct evolutionary relationship between the animal phleboviruses and the plant tenuiviruses. PMID- 8468560 TI - The putative zinc finger of a caulimovirus is essential for infectivity but does not influence gene expression. AB - Plant pararetroviruses, such as caulimoviruses, and animal retroviruses have in common the presence of a highly conserved arrangement of cysteines and a histidine in the precursor of the capsid protein. The composition of these amino acids resembles a zinc finger element, a structure that is common to a class of eukaryotic proteins that regulate gene expression. The role of the putative zinc finger in the life-cycle of caulimoviruses was investigated by introducing specific mutations in the coat protein coding region of a cloned and infectious form of figwort mosaic virus, a caulimovirus. This mutated viral genome, which no longer encoded the conserved cysteine and histidine residues, was not infectious in plants. Transient expression assays in protoplasts showed that expression of a reporter gene inserted at different places in the genome was not detectably influenced by the coat protein or its putative zinc finger. It appears that the zinc finger-like element of caulimoviruses is not involved in the regulation of gene expression. These observations support a model which predicts a function of the zinc finger in specific recognition and packaging of viral RNA into virions prior to reverse transcription. PMID- 8468561 TI - Production of infectious in vitro transcripts from a full-length clover yellow mosaic virus cDNA clone. AB - A full-length cDNA copy of clover yellow mosaic virus (CYMV) RNA was constructed from two smaller cDNA clones. In vitro transcription of linearized plasmid with T7 RNA polymerase produced genomic-sized RNA. These transcripts caused symptoms typical of CYMV infection when used to inoculate both a systemic host (Vicia faba) and a local lesion host (Gomphrena globosa). Electron microscopy of extracts from individual local lesions revealed virus particles identical to native CYMV. Increasing the length of the poly(A) tail from 23 residues to 80 or to 135 residues increased the infectivity rate from 12% to 17% or to 35% that of native CYMV RNA, respectively. PMID- 8468562 TI - The nucleotide sequence of the M RNA segment of tomato spotted wilt virus, a bunyavirus with two ambisense RNA segments. PMID- 8468563 TI - Comparative study of the isolation of human immunodeficiency virus from the lung and peripheral blood of AIDS patients. AB - HIV-1 proviral DNA was detected by the polymerase chain reaction (PCR) in leucocytes from the peripheral blood (PBL) and bronchoalveolar lavage (BAL) of 100% and 72%, respectively, of HIV-1 seropositive patients. Infective virus isolated by cocultivation was recovered from the PBL and BAL of 50% and 59% of individuals, respectively. Isolation of HIV-1 was more readily made from the lung of individuals undergoing Pneumocystis carinii pneumonia (PCP) than from patients with non-PCP lung infections. The concomitant infection of lung cells with cytomegalovirus did not affect the isolation rate of HIV-1 from the lung. HIV-1 was isolated from BAL of 23 out of 36 (64%) individuals receiving no antiviral chemotherapy and from 13 out of 24 (54%) patients who were receiving AZT. PMID- 8468564 TI - Delayed clearance of HBV-DNA detected by PCR in the absence of viral replication. AB - The polymerase chain reaction (PCR) was used to study the in vivo persistence and clearance of HBV-DNA in the serum of a monkey (Macaca mulatta) known to be naturally resistant to the HBV infection. Total infectious plasma, virus pellet, and viral DNA were inoculated into 3 different monkeys. Degradation of infectious particles and clearance of HBV-DNA were analyzed by detecting HBV-DNA sequences in serial dilutions of serum by dot blot hybridization and PCR. Semi-quantitation was carried out by comparison with minimal positive dilutions of known HBV-DNA. The presence of hepatitis B surface antigen (HB-sAg) and hepatitis B e antigen (HBeAg) in serum was also investigated. PCR assays were found positive in serial samples of the 3 monkeys, and passively transmitted viral DNA remained detectable for 3 months after inoculation. HBsAg and HBeAg were detectable for 3 weeks and 2 weeks, respectively, in a monkey inoculated with total infectious plasma. Semi quantitation of HBV viremia showed that the amount of virus detected 1 day after injection was markedly decreased and persisted at a low level, showing a rapid and important sequestration of viral particles. Since replication can be excluded in these monkeys, the data show that HBV-DNA sequences can remain detectable at a low level in the serum for long periods. It is thus conceivable that PCR may also detect the HBV genome, eventually degraded in vivo, and a weakly positive result does not always mean ongoing viral replication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468565 TI - Polymerase chain reaction-based detection of hepatitis D virus genome in patients infected with human immunodeficiency virus. AB - The polymerase chain reaction (PCR) was used to detect hepatitis D (HD) viremia in patients infected with the human immunodeficiency virus (HIV). Nineteen (9%) of 206 such patients, unselected for liver disease or HBV infection, were found prospectively to be infected by HDV. Thirty-one anti-HIV-positive patients were studied by means of PCR, and the results were analyzed according to HDV and hepatitis B virus (HBV) serological status. HDV-PCR was positive in 5 patients. Two had detectable serum HDV antigen. Four patients had anti-HD IgM and IgG antibodies. All these patients were HBs antigen-positive, and 3 were HBV-DNA positive. All the other patients were HDV-PCR-negative. Statistical analysis suggested more extensive liver damage and immunological impairment in HDV-PCR positive patients. In this unselected HIV-infected population, HDV-RNA detection by PCR was restricted to HDV infected patients in whom 5/19 were positive. This test permitted direct diagnosis of HDV viremia and will be useful for monitoring HDV infection. PMID- 8468566 TI - Small virus-like particles bud from the cell membranes of normal as well as HIV infected human lymphoid cells. AB - Electron microscopy (EM) of cell sections showed cell associated virus-like particles (VLP), 50-60 nm in diameter, budding from the membrane of human lymphoid cells in culture. The particles had an envelope continuous with the cell membrane and a dense core that almost filled the particle. Particles 70-80 nm in diameter with prominent external spikes were found in the culture medium by negative staining (medium-associated VLP). Cell-associated VLP were also present in cord lymphocytes, both on initial separation and after culture with or without foetal calf serum, and therefore were considered to be endogenous to the cells and were not bovine diarrhoea virus. VLP were observed in most of the lymphoid cell lines examined. VLP were also found less frequently in established human tumour and nontumour cell lines. Both cell-associated and medium-associated VLP were also present in HIV infected cell cultures, and they could be distinguished from HIV by their characteristic morphology and smaller size. It was not determined whether the 2 types of particle represented the same entity, or whether they were defective virus particles or a cellular secretory product. PMID- 8468567 TI - Incidence of HTLV-I/II infection in seronegative high-risk individuals. AB - The frequency of human T-cell lymphotropic virus types I and II (HTLV-I/II) polymerase chain reaction (PCR) reactivity was studied in two groups of high-risk individuals in Amsterdam: hard drug users and heterosexual outpatients of the sexual transmitted diseases (STD) clinic. Both groups were seronegative as determined by enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and radioimmuno-precipitation assay (RIPA). Detection of HTLV-I and HTLV-II in peripheral blood mononuclear cells (MNC) was performed by PCR, using primer sets indicative for the pol and tax genes. In the hard drug users group (n = 25) no evidence of HTLV-I/II infection was found whereas in the STD group (n = 21) one individual was identified with HTLV-II proviral DNA. Positive reactions in PCR were confirmed only for three seropositive controls after in vitro culture of MNC but not for the PCR-positive, seronegative individual. Virus production in vitro could not be detected by a sensitive HTLV-I antigen capture assay for viral p24gag proteins after in vitro T-cell stimulation of MNC, either from PCR positive or PCR-seronegative individuals. This suggests again a low viral production rate. It is concluded that infection with HTLV-II can be detected among high-risk seronegative individuals. PMID- 8468568 TI - Critical review of Aedes aegypti control programs in the Caribbean and selected neighboring countries. AB - In recent years the region of the Americas has experienced increasing dengue activity with circulation of multiple virus serotypes. Associated with this trend has been the occurrence of sporadic dengue hemorrhagic fever (DHF) cases and of DHF epidemics in both the Caribbean and Latin America. High vector infestation levels persist even though most countries in the Caribbean conduct national Aedes aegypti control programs and despite the fact that in some instances, expenditures exceed US$5 per capita per annum. This paper critically reviews the resources and vector control strategies employed in the region and in selected neighboring countries. Reasons for the lack of progress include continued overreliance on eradication-style larviciding routines and the passive role of communities in addressing the problem. A policy of health promotion aimed at improving environmental health practices at the household and community levels has been endorsed by the governments of the region but as yet has not been widely adopted. PMID- 8468569 TI - Effect of the insect growth regulator methoprene on the ovipositional behavior of Aedes aegypti and Culex quinquefasciatus. AB - Laboratory and field tests were conducted to determine the attractiveness of the insect growth regulator methoprene to ovipositing mosquitoes when presented at concentrations used in mosquito control programs. Laboratory experiments indicated that ovipositing Culex quinquefasciatus and Aedes aegypti were not attracted to methoprene. In field experiments, Culex stigmatosoma and Cx. quinquefasciatus larval dip counts in experimental ponds treated with methoprene briquets were not significantly different from untreated control ponds. Water taken from these methoprene-treated ponds was not attractive when compared with water taken from untreated ponds to ovipositing Cx. quinquefasciatus in laboratory experiments. These studies provide strong evidence that methoprene is not attractive to ovipositing mosquitoes at concentrations within the range of field applications. PMID- 8468570 TI - Role of Anopheles culicifacies s.l. and An. pulcherrimus in malaria transmission in Ghassreghand (Baluchistan), Iran. AB - A 2-site immunoradiometric assay (IRMA) was performed on the head and thorax of Anopheles culicifacies s.l. and An. pulcherrimus females, the 2 most common anopheline species in the District of Ghassreghand (Baluchistan, Iran), collected during the 2 peak malaria transmission seasons (May and September-October 1991). Positive IRMA results revealed the 2 species as potential vectors of malaria in this highly endemic district. This finding serves as the first report on natural infection of An. pulcherrimus in Iran and is the second on natural infection of An. culicifacies since the previous report of 1959. PMID- 8468571 TI - Anopheles culicifacies complex: cytogenetic characterization of Rameshwaram island populations. AB - Anopheles culicifacies sensu lato collected from Rameshwaram island, Tamil Nadu state, India was identified as species B based on the diagnostic inversion karyotype Xab 2g1+h1 as observed in polytene chromosomes. Among male mitotic karyotypes made from larval neurogonial cells, two types were observed: one with an acrocentric Y-chromosome and the other with a sub-metacentric Y-chromosome, both had sub-metacentric X and metacentric autosomes. The Rameshwaram population is identical to species B in its genetic relationship with species A and C as determined by experimental hybridizations (sterile and fertile male hybrids, respectively). PMID- 8468572 TI - A comparison of Teflon slides and the Army Insecticide Measuring System for sampling aerosol clouds. AB - The effects of method of droplet analysis, reader of Teflon slides and distance on mass median diameter of a Cythion aerosol cloud were examined in the calibration of an Army Insecticide Measuring System (AIMS). There were no significant differences in results among readers and between the AIMS and readers. There were slight but statistically significant differences between readers of Teflon slides and between the methods of analysis. Data supports the manufacturer's recommendation that, for the AIMS, the distance at which an aerosol generator air blast is between 3 and 7 m3 s-1 must be determined. PMID- 8468573 TI - Factors affecting the acquisition of Plagiorchis noblei (Trematoda: Plagiorchiidae) cercariae by black fly (Diptera: Simuliidae) larvae and the effect of metacercariae on host survival. AB - Larvae of 4 species of black flies, Prosimulium mixtum, Simulium vittatum, S. decorum and Stegopterna mutata, were exposed in the laboratory to cercariae of the digenean Plagiorchis noblei in flowing water. Prevalence and intensity of infection of all species varied directly with exposure intensity and decreased with increasing water velocity; prevalence increased with larval size. Infection levels for P. mixtum were higher than for the 3 other species. Mortality among infected larvae of all species was 3 times that of controls. Exposure of black fly larvae to P. noblei cercariae may adversely affect their survival. PMID- 8468574 TI - Dynamics of population densities and vegetation associations of Anopheles albimanus larvae in a coastal area of southern Chiapas, Mexico. AB - Spatial and seasonal variations on Anopheles albimanus larval densities and their plant associations were investigated in larval habitats in southern Mexico between April 1989 and May 1990. Thirty-four plant groups were dominant in larval habitats. Dense larval populations were associated with 3 genera of plants, Cynodon, Echinocloa and Fimbristylis and no larvae were found in habitats with Salvinia and Rhizophora. Low significant positive or negative associations were documented with the other 12 plant genera. Larval habitats were classified according to the morphology of their dominant plants. Higher larval densities were observed in the groups characterized by relatively short emergent vegetation. The distribution of habitat-types within 5 identified vegetation units showed a significantly dependent relationship. For the entire study period, highest larval densities were detected in flooded pasture/grassland vegetation units. For all vegetation units, higher larval densities were found when the dominant plant type covered between 25-50% of the breeding site. The integration of data from habitat-types into vegetation units did not result in loss of information. PMID- 8468575 TI - Metaphase karyotypes of Anopheles of Thailand and Southeast Asia: I. The Hyrcanus Group. AB - Metaphase karyotypes of 6 species of the Hyrcanus Species Group of the subgenus Anopheles show constitutive heterochromatin variation in X and Y chromosomes. Anopheles peditaeniatus exhibits the most extensive variation in the size and shape of heterochromatic sex chromosomes, with 3 types of X and 5 types of Y chromosomes. Anopheles nitidus shows the least variation, with only 2 types of X chromosomes. Anopheles sinensis and An. crawfordi each have 2 forms of metaphase karyotype in the heterochromatin of the Y chromosome. It is not known whether the 2 forms of metaphase karyotype in these 2 species represent inter- or intraspecific differences. The 2 forms of heterochromatic sex chromosomes observed in An. argyropus and An. nigerrimus may suggest the existence of sibling species complexes within each of these species. PMID- 8468576 TI - Experimental infection of Anopheles gambiae s.s., Anopheles freeborni and Anopheles stephensi with Plasmodium malariae and Plasmodium brasilianum. AB - Susceptibility to infection of 2 strains of Anopheles gambiae s.s., An. freeborni and An. stephensi, was determined for 2 closely related malaria parasites, Plasmodium malariae and P. brasilianum. Neither strain of An. gambiae supported development of oocyst densities as great as the other 2 anopheline mosquitoes. The ZAN strain of An. gambiae s.s. from Zanzibar was more susceptible to infection with the strain of P. malariae from Uganda than the G-3 strain of An. gambiae s.s. from The Gambia. All species and strains of mosquitoes supported complete development to the presence of sporozoites in the salivary glands. PMID- 8468577 TI - Effect of controlled burning on survival of floodwater Aedes eggs in Kenya. AB - The effect of controlled burning on the survival of Aedes mosquito eggs was evaluated in 2 distinct dambo habitats. In a dambo dominated by grasses, egg survival was 3.3% after burning compared with 43.8% in a similar dambo that was not burned. In a dambo dominated by sedges, egg survival was 0.7% after burning compared with 28.5% in a similar dambo that was not burned. Mortality of mosquito eggs appeared to be caused by high temperatures associated with the fire and not elapsed time since egg survival did not decrease with time after burning. The potential for burning to control the mosquito vectors of Rift Valley fever virus is discussed. PMID- 8468578 TI - Reducing the overwintering ability of Aedes albopictus by male release. AB - Eggs of temperate Aedes albopictus populations are cold hardy and can diapause, but tropical populations are not cold hardy and cannot diapause. Heterozygotes possess intermediate diapause and cold hardiness. Males of a tropical strain from Malaysia with a distinctive genetic marker were released into an existing temperate population in East St. Louis, Illinois. Subsequent egg samples from the release site had genetic marker frequency of up to 24%. Reduced cold hardiness and decreased diapause incidence were also observed in the release site population. No such changes occurred at a nearby control site. The rank order of overwintering survival of eggs at the release site was: Aedes triseriatus > temperate Ae. albopictus > hybrid temperate/tropical Ae. albopictus > tropical Ae. albopictus. Eggs collected from the release population the next summer showed total absence of the genetic marker; presumably carriers were removed by the winter. PMID- 8468580 TI - Assessment of Aedes sierrensis as a vector of canine heartworm in Utah using a new technique for determining the infectivity rate. AB - Both Aedes sierrensis and Dirofilaria immitis have recently become established in Utah. We evaluated the vector potential of this Aedes sierrensis strain using a new technique for detecting Dirofilaria immitis in individual mosquitoes. Survival of Aedes sierrensis females after bloodfeeding did not differ from that of Ae. triseriatus but infective Ae. sierrensis produced significantly more L3 nematodes. This observation and epidemiological data support the hypothesis that Ae. sierrensis is the vector of canine heartworm in Utah. Infectivity was determined by counting infective-stage parasites that migrated into the medium after individual mosquitoes were decapitated or crushed in the wells of tissue culture plates. Complete recovery of infective-stage nematodes was attained in 60 74% of the mosquitoes and 77-93% of all L3 were collected with this technique. There were few false negatives. High recovery rates (mean = 89%) were also obtained for mosquitoes treated en masse. PMID- 8468579 TI - Larvicidal and chemosterilant activity of Annona squamosa alkaloids against Anopheles stephensi. AB - Alkaloids isolated from Annona squamosa have shown larvicidal growth-regulating and chemosterilant activities against Anopheles stephensi at concentrations of 50 to 200 ppm. Adults exposed as larvae to different treatments showed reduced fecundity and fertility in females. Mortality in the larvae, pupae and adults produced about a 52-92% decrease in the laboratory experiment. The total developmental period was slightly reduced from the control. Treatment with the alkaloids had a significant effect on the mortality, emergence and reproductive physiology of An. stephensi. PMID- 8468581 TI - Malathion aerosol cloud behavior in a Coastal Plains pine flatwoods. AB - The study examines malathion aerosol cloud behavior in a North Florida pine flatwoods. Droplet mass median diameters (MMD) decreased over distance in both open and pine flatwoods. A sharp decrease in number of aerosol droplets per cm2 occurred between 3.1 and 15.2 m and a gradual decline in droplets per cm2 occurred beyond 15.2 m in both treatment areas. There were no interactions between habitat and distance in regard to MMD or droplets per cm2. Analysis of variance models accounted for 82% of the variability in the MMD data and 79% of the variability in the number of droplets per cm2. PMID- 8468582 TI - Carbon dioxide anesthesia in phlebotomine sand flies (Diptera: Psychodidae): CO2 effect upon two laboratory colonies. AB - Gravid females of 2 sand fly species, Phlebotomus papatasi and P. perniciosus, were exposed to carbon dioxide anesthesia for 5, 10 and 20 minutes. Recovery time, mortality at 0 min and 24 h, percentage of females laying eggs, time to oviposition, and egg productivity for each exposure time were registered. Survival, fecundity and oviposition time in the 2 species were not adversely affected by the short period of CO2 anesthesia routinely used in the sand fly colony maintenance. PMID- 8468583 TI - Functional imaging in relation to parkinsonian syndromes. AB - Parkinsonism is a feature not only of Parkinson's disease but also of many other diseases affecting basal ganglia function. Functional imaging (PET and SPECT) can demonstrate the various resting patterns of disruption of regional cerebral blood flow, metabolism, and neuropharmacology associated with different parkinsonian disorders. 18F-dopa PET also has the potential to detect subclinical dysfunction of dopaminergic terminals in at-risk subjects. Finally, functional imaging can help us understand the nature of the networks involved in performing different motor tasks, and can reveal how these networks malfunction in the presence of bradykinesia or parkinsonian tremor. PMID- 8468584 TI - Inverse correlation between disappearance of intrathecally injected 111In-DTPA from CSF with CSF protein content and CSF-to-serum albumin ratio. AB - By means of cerebrospinal fluid (CSF) scintigraphy with 111In-DTPA injected following lumbar puncture in 18 patients after meningitis (12), with traumatic head injury (4), cholesteatoma (1) or a communicating hydrocephalus (1) the hypothesis of whether slow movement of CSF may contribute to the elevation of CSF protein and albumin content in neurological diseases other than spinal block was tested. The ratios of the count rates over the head (geometric mean of anterior and posterior view) at 23-25 h to 4-6 h after 111In-DTPA application (C24 h/C5 h) and the ratio 47-49 h to 23-25 h after injection (C48 h/24 h) were taken as measures of the velocity of 111In-DTPA disappearance from CSF. Both the CSF protein content and the CSF-to-serum albumin ratio correlated with C24 h/C5 h and C48 h/C24 h. Assuming log-linear elimination between 24 and 48 h the elimination half-life of 111In-DTPA was estimated to be 12.4-131.1 h (median = 31.7 h). It was concluded that slow CSF kinetics probably are involved in the elevation of CSF protein content in several neurological diseases. PMID- 8468585 TI - Reduction in cortical 5-HT3 binding sites following a unilateral 6 hydroxydopamine lesion of the medial forebrain bundle in rats. AB - Serotonergic mechanisms have been implicated in pathophysiology of Parkinson's disease, an illness where the dopamine deficiency represents the prime biochemical deficit. Present interest centres on the possible involvement of serotonergic receptors in modulating dopamine transmission. In this paper the binding of the selective 5-HT3 antagonist [3H]GR 65630 was studied in rats with a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. The maximal density of specific [3H]GR 65630 binding was reduced in homogenates of entorhinal (17.1%, P < 0.05) and prefrontal cortex (27.5%, P < 0.05) on the lesioned side of the rat brain compared to the control tissues. An increase in affinity for [3H]GR 65630 binding was also found in homogenates of prefrontal cortex (33.8%, P < 0.05). No changes in the characteristics of [3H]GR 65630 binding to homogenates from the amygdala and hippocampus were observed. These data suggest that altered dopamine function may affect serotonergic mechanisms in the cortex in Parkinson's disease. PMID- 8468586 TI - Chronic progressive spinocerebellar syndrome associated with antibodies to human T-lymphotropic virus type I: clinico-virological and magnetic resonance imaging studies. AB - The relationship between HTLV-I infection and the development of spinocerebellar degeneration (SCD) in adulthood was studied. The frequency of anti-HTLV-I antibodies among patients with SCD (8 of 43, 19%) was found to be higher than the seroprevalence rate in the northern part of Kyushu island (6%). All HTLV-I carriers with SCD showed chronic progressive cerebellar ataxia as a predominant feature and cerebellar atrophy was evident in 6 of 8 patients on magnetic resonance imaging (MRI) of the brain. However, SCD patients with anti-HTLV-I antibodies showed a significantly higher frequency of cerebral white matter lesions on brain MRI (6 of 8) and pyramidal tract signs in lower extremities (6 of 8) than did those without the antibodies (35%, P < 0.05 and 26%, P < 0.01, respectively). Moreover, the HTLV-I carriers with SCD exceeded 14 HTLV-I carriers having neither SCD nor HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (21%, P < 0.05), and 59 HTLV-I seronegative patients without brain disorders (19%, P < 0.001) in the frequency of white matter lesions. On the other hand, the HTLV-I carriers with SCD were distinct to the HAM/TSP patients in the predominance of cerebellar involvement. Therefore, the peculiar features of cerebellar, pyramidal and white matter involvement in the HTLV-I-seropositive SCD patients as well as the increased frequency of HTLV-I infection among SCD patients suggest that this syndrome may be a distinct subtype of HTLV-I associated neurologic diseases. PMID- 8468587 TI - Intrathecal synthesis of interleukin-2 and soluble IL-2 receptor in asymptomatic HIV-1 seropositive individuals. Correlation with local production of specific IgM and IgG antibodies. AB - The relationship between the interleukin-2 (IL-2) system and the humoral response against human immunodeficiency virus type-I (HIV-1) is important in understanding the immune reaction before the development of AIDS. Levels of IL-2 and soluble IL 2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured and correlated with levels of anti-1 IgG and IgM antibodies. High IL-2 levels were detected in the CSF of 20 (65%) subjects, 18 (90%) of whom had evidence of intrathecal synthesis of HIV-1-specific IgM antibodies. Similarly, IgG antibodies were detected in 10 subjects who had elevated IL-2 levels in the CSF. Moreover, intrathecal levels of IL-2 and sIL-2R correlated with intrathecal synthesis of both IgG and IgM antibodies. Local release of IL-2 seems to play an important role in the initiation of the antibody response against HIV-1 in early stages of infection and may be utilised in devising effective therapeutic strategies. PMID- 8468588 TI - Copper-zinc superoxide dismutase activity in red blood cells and serum in demented patients and in aging. AB - The activity of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD) has been investigated in serum and red blood cells (RBC) homogenate obtained from demented patients with associated vascular lesions (VD), demented patients with probable Alzheimer's disease (DAT) and healthy controls (CG) of the same age. The increase in SOD activity was statistically significant (P < 0.01) in RBCs homogenate of DAT and VD patients, when compared to controls, but no differences appear between the two diseases groups. Additionally, a statistically significant increase in SOD activity (P < 0.01) in DAT patients above 70 years as compared to those 50-70 years old, and a relation between SOD and age were found. No changes in SOD activity with age in healthy controls nor in vascular dementia group were detected. A statistically significant increase in Circulating SOD activity (P < 0.01) was observed in vascular patients compared to controls. The observed increase in DAT Circulating SOD activity (against CG) was not significant. The increased levels of Cu-Zn SOD, probably represent a general alteration of the oxidative processes characteristic of these dementias and suggest that the enzyme might be used as a marker. PMID- 8468589 TI - Determination of serum and brain concentrations of neuroprotective and non neuroprotective doses of MK-801. AB - We developed a sensitive and reliable gas chromatographic (GC) technique for the quantitative analysis of MK-801 in brain and serum and applied the technique to investigate tissue concentrations of neuroprotective and non-neuroprotective doses of MK-801 in a neonatal rat model of hypoxic-ischemia. Brain concentrations of MK-801 were a linear function of dose over 4 orders of magnitude. After administration of a neuroprotective dose of MK-801 (29.6 mumol/kg) to control rats, both serum and brain concentrations rose rapidly to approximately 300 nM and approximately 2000 nM, respectively, within 30 min. Approximately 60% of serum and 90% of brain MK-801 were bound leaving the free concentrations in both blood and brain at approximately 100-200 nM. After hypoxic-ischemia, serum MK-801 concentrations were not different from controls but brain concentrations were lowered by 32%. Free brain concentrations of MK-801 after hypoxic-ischemic were 124 nM after 29.6 mumol/kg while after 8.9 mumol/kg (the non-neuroprotective dose) they were 39 nM. In view of the slow kinetics of MK-801 channel blockade, which never reaches equilibrium during the current experiment, this difference in concentration would be expected to result in an 80-fold (or greater) difference in the current flux through NMDA receptor-operated ion-channels as the rate of NMDA receptor-operated ion-channel blockade is concentration dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468590 TI - Evoked potential measures of auditory cortical function and auditory comprehension in aphasia. AB - This study investigated the relation between severity of auditory comprehension impairment in aphasia and the functional integrity of the posterior superior temporal region as evaluated by middle- and long-latency auditory evoked potentials and dipole source analysis. AEPs were studied in 20 stroke patients and in age-matched controls. AEPs and language data were collected 1 year or more post onset, and were compared to performance early after onset. Patients were differentiated in a group with severe and a group with moderate to recovered auditory comprehension impairment. Significant asymmetries of auditory evoked dipole source potentials were more frequent in the severely impaired group. However, a severe auditory comprehension deficit was not incompatible with normal AEPs. The results confirm the importance of the posterior superior temporal region for auditory language comprehension, but the correlation between AEP asymmetry and auditory comprehension seems due to the close spatial relation of AEP generating substrate and posterior language area rather than to partial overlap. Dipole source analysis of AEPs proved to be a valuable method for the assessment of interhemispheric asymmetries, enhancing the sensitivity of AEPs to unilateral damage of auditory cortex. PMID- 8468591 TI - Antibody-dependent cell-mediated cytotoxicity (ADCC) in Parkinson's disease. AB - The possible role of a non-specific cell-mediated immune reaction in the pathogenesis of Parkinson's disease (PD) is discussed. It was found that the killer cell activity of PD patients below 60 years of age was significantly lower than in the older age groups or in the age-matched control group. On the other hand, it was also found that the killer cell activity of PD patients with severe symptoms (Hoehn-Yahr's IV, V stage) was significantly higher than that of the milder cases. These results support the hypothesis that an ADCC reaction- mediated by the killer cells--may play a role in the pathogenesis of PD. PMID- 8468592 TI - Lewy body-like inclusions in Onuf's nucleus from two cases of sporadic amyotrophic lateral sclerosis. AB - Lewy body-like inclusions in Onuf's neurons from two sporadic cases with amyotrophic lateral sclerosis (ALS) were reported. These inclusions in Onuf's neurons as well as those found in the anterior horn cells were immunostained with an anti-ubiquitin antibody. Neuropathological examination of these two cases revealed neuronal loss and associated gliosis in the anterior horn of the spinal cord and hypoglossal nuclei, and degeneration of the corticospinal tract. In addition to Lewy body-like inclusions, ubiquitinated skein-like inclusions, Bunina bodies, or both were observed in the cytoplasm of the remaining neurons in the anterior horn of the spinal cord, and, to a lesser degree, in Onuf's nucleus. Spheroids and cord-like thickening of cell processes were also found in the anterior horn of the spinal cord. Histometrical study of Onuf's nucleus revealed atrophy and loss of Onuf's neurons from Case 1 with a long clinical course. Similar cases of motor neuron disease with or without tract degeneration have been reported, but the presence of Lewy body-like inclusions in Onuf's nucleus is reported here for the first time. It is suggested that Onuf's nucleus is more or less involved in the degenerative process characteristic of ALS. PMID- 8468593 TI - Electrophysiological study of dorsal column function in streptozocin-induced diabetic rats: comparison with 2,5-hexanedione intoxication. AB - Dorsal column function and peripheral motor and sensory conduction velocities (MCV, SCV) were evaluated in experimental diabetic rats and compared with those in 2,5-hexanedione (2,5-HD) intoxicated rats. Hyperglycemia was induced by a single injection of streptozocin, and electrophysiological studies were performed 4 and 12 weeks after the injection. For 8 weeks 2,5-HD was administered daily by drinking water to make the 2,5-HD neuropathy rats. Age-matched rats were used as control. In diabetic rats, gracile surface potentials evoked by electrical stimulation of the lumbosacral trunk remained normal during the experimental period, whereas the N and P waves of the evoked potentials were suppressed and the duration of the N wave was prolonged in the 2,5-HD rats. In 4-week diabetic rats, the antidromic compound action potentials of the gracile tract recorded at the most proximal site of lumbosacral trunk were normal. In 12-week diabetic rats, the gracile tract conduction velocity (GTCV) was decreased, although the duration of these potentials was normal. By contrast, the GTCV was decreased and the duration was markedly prolonged in 2,5-HD rats. These findings might indicate that temporal dispersion of incoming volleys in the gracile tract is increased in 2,5-HD rats, but not in diabetic rats. These results suggest that diabetic myelopathy exists that but the magnitude and progression of this condition are quite different from those of 2,5-HD intoxication, typical dying-back-type neuropathy and that the dorsal column is less vulnerable than the peripheral nerve in diabetes mellitus. PMID- 8468594 TI - Cerebrotendinous xanthomatosis: pathophysiological study on bone metabolism. AB - A condition of osteopenia in some cerebrotendinous xanthomatosis (CTX) patients led us to investigate bone metabolism in 8 patients belonging to 5 families. Serum calcium, phosphate and vitamin D metabolites were in the normal range; a reduction in total body density and impairment of intestinal radiocalcium absorption were found in the majority of our patients. PMID- 8468595 TI - Regulation of membrane-mediated chronic muscle degeneration in dystrophic hamsters by calcium-channel blockers: diltiazem, nifedipine and verapamil. AB - Membrane-mediated excessive intracellular calcium accumulation (EICA) is a fundamental pathogenetic event associated with chronic muscle degeneration in patients with Duchenne muscular dystrophy (DMD), and in animals with hereditary muscular dystrophy (HMD). Because of potential Ca(2+)-channel blocking properties, we investigated the relative efficacies of chronic diltiazem (DTZM) (50 mg/kg/d), nifedipine (NFDN) (6 mg/kg/d), and verapamil (VPML) (25 mg/kg/d) therapies in reducing EICA and improving dystrophic pathobiology beginning in 30 day-old male BIO-14.6 strain dystrophic hamsters (DH). Each agent, and sterile distilled water as vehicle control, was given in a single daily oral dose for 180 days to four groups each of DH and BIO-F1B strain normal hamsters (NH). Plasma [Ca] and [Mg]; plasma aldolase (ALD), creatine kinase (CK), and lactate dehydrogenase (LDH) activities; relative cardiac hypertrophy and relative soleus hypertrophy; tissue [Ca] and [Mg] of the heart and rectus femoris muscle, histology of rectus femoris, and overall mortality rate were quantitated. Muscle Mg was not modified in DH, or by any of these agents. NFDN produced significant edema in the soleus and myocardium. During the 6-month therapeutic trial, 45% DH and 18% NH died on VPML, 27% DH and 9% NH on NFDN, and 20% DH controls on distilled water, but none on DTZM; suggesting that DTZM treated DH lived longer than DH controls. Relative efficacy in regulating EICA in both the cardiac and skeletal muscles; plasma ALD, CK, and LDH; and improving associated dystrophic pathobiology was found to be DTZM >>> NFDN > VPML. DTZM appears to be the most effective and safest agent in mitigating EICA in cardiac and skeletal muscles, efflux of intracellular enzymes, histopathology of dystrophic muscle with sporadic necrosis, and chronic muscle degeneration in DH with HMD. DTZM therapy also halted the high morbidity and mortality associated with the dystrophic pathobiology inherent in DH. PMID- 8468596 TI - Manifesting heterozygotes in McArdle's disease: clinical, morphological and biochemical studies in a family. AB - We report a family with McArdle's disease with several affected individuals in two generations. This unusual pedigree for an autosomal recessive disease is explained by the existence of manifesting heterozygotes in the maternal line. The presence of symptoms in heterozygotes seems to be due to a decrease in myophosphorylase activity below a critical threshold, ranging between 30% and 45% of normal mean value. The occurrence of several manifesting heterozygotes in the maternal line only can be explained by compound heterozygosity of a defective allele and a pseudodeficient allele for myophosphorylase, or by a genetic factor which regulates the phenotypic expression of the gene. PMID- 8468597 TI - Paul C. Bucy. 1904-1992. PMID- 8468598 TI - Decompressive lumbar laminectomy for spinal stenosis. AB - A total of 258 consecutive decompressive lumbar laminectomies performed on 244 individuals presenting with spinal stenosis were analyzed retrospectively. Spinal fusion was avoided in all but two patients. Outcome in terms of pain relief and return to normal activity was evaluated in two stages, one derived from patient charts and having a relatively short-term follow-up time (mean 8.4 months) and a second derived from patient responses to a questionnaire (which also scored for satisfaction with the results of surgery), which had a longer follow-up time (mean 4.7 years). More than 20 clinical and operative parameters were analyzed. Overall, a high degree of success (93% pain relief, 95% return to normal activity) was achieved in the short term, which was supported by the longer-term follow-up data (64% pain relief, 56% activity return, 75% satisfaction). The following factors were not significantly correlated with outcome: patient age; sex; worker's compensation or no-fault insurance status; employed versus not employed; a history of back surgery prior to the laminectomy studied; existence of degenerative spondylolisthesis or scoliosis; complete versus incomplete myelographic block; or the level of the lumbar spine undergoing surgery. The major conclusions arising from these data are: 1) for all age groups through at least the eighth decade of life, decompressive lumbar laminectomy is a relatively safe operation having a high medium-to-long-term success rate; 2) lumbar instability following laminectomy is rare, even in individuals presenting prior to surgery with degenerative instability conditions; and 3) lumbar fusion in addition to the decompressive laminectomy procedure is rarely required for degenerative spinal stenosis. PMID- 8468599 TI - Halifax interlaminar clamp for posterior cervical fusion: a long-term follow-up review. AB - Fifty consecutive patients requiring posterior cervical fusion for various pathologies were treated with Halifax interlaminar clamps for internal spinal fixation. Fusion involved the C1-2 level in 17 cases, the C1-3 level in one, and the lower cervical area (C2-7) in 32. No patient was lost to follow-up review, which varied from 6 to 40 months (average 21 months). Fusion failed in five patients, three at the C1-2 level, one at the C1-3 level, and one at the C2-3 level. Screw loosening was the cause of failure in four patients, and in one the arch of C-1 fractured. No other complications occurred. Because of the lack of complications, avoidance of the hazards of sublaminar instrumentation, and an excellent fusion rate, this technique is highly recommended for posterior cervical fusion in the lower cervical spine. Atlantoaxial arthrodesis was achieved in only 14 (82%) of 17 patients, however, which might be due to the higher mobility at this multiaxial level. Improved results in this region may be possible by using a new modified interlaminar clamp, by performing adequate bone fusions, and by postoperative external halo immobilization in high-risk patients. PMID- 8468600 TI - Clinical and electroneurographic evaluation of sensory/motor-differentiated nerve repair in the hand. AB - In 17 patients acetylcholinesterase activity was used to differentiate between sensory and motor fascicles in median and ulnar nerve repair of the hand. Eleven patients received follow-up evaluation 1 to 11 years after surgery, and at that time clinical and electroneurographic examinations were performed to evaluate the techniques. Clinical examination showed that four patients had regained on average 71.9% of hand function after median nerve repair, one patient had regained 83.6% of hand function after ulnar nerve repair, four patients had regained on average 53.3% of hand function after median and ulnar nerve repair, and two patients had regained on average 43.5% of hand function after median and partial ulnar nerve repair. The contribution of the ulnar nerve to reinnervation of the thenar muscles was 68.5%, whereas the median nerve did not contribute to reinnervation of the hypothenar muscles. Distal latencies for the median nerve showed a delay of 36% of the upper limit of normal value, and those for the ulnar nerve revealed a delay of 21.5%. This study demonstrated that sensory/motor differentiated nerve repair of the median and ulnar nerves is possible and can be proven electroneurographically. PMID- 8468601 TI - The surgical treatment of painful traumatic neuromas. AB - Pain following suspected nerve injury was comprehensively evaluated with detailed examination including history, neurological evaluation, electrodiagnostic studies, quantitative sensory testing, thermography, anesthetic agents, and sympathetic nerve blocks. Forty-two surgically treated patients fell into four discrete groups: Group 1 patients had distal sensory neuromas treated by excision of the neuroma and reimplantation of the proximal nerve into muscle or bone marrow; Group 2 patients had suspected distal sensory neuromas in which the involved nerve was sectioned proximal to the injury site and reimplanted; Group 3 patients had proximal in-continuity neuromas of major sensorimotor nerves treated by external neurolysis; and Group 4 patients had proximal major sensorimotor nerve injuries at points of anatomical entrapment treated by external neurolysis and transposition, if possible. Patient follow-up monitoring from 2 to 32 months (average 11 months) was possible in 40 (95%) of 42 patients. Surgical success was defined as 50% or greater improvement in pain using the Visual Analog Scale or pain relief subjectively rated as either good or excellent, without postoperative narcotic usage. Overall, 16 (40%) of 40 patients met those criteria. Success rates varied as follows: 44% in 18 Group 1 patients, 40% in 10 Group 2 patients, 0% in five Group 3 patients, and 57% in seven Group 4 patients. Twelve (30%) of 40 patients were employed both pre- and postoperatively. It is concluded that: 1) neuroma excision, neurectomy, and nerve release for injury-related pain of peripheral nerve origin yield substantial subjective improvement in a minority of patients; 2) external neurolysis of proximal mixed nerves is ineffective in relieving pain; 3) surgically proving the existence of a neuroma with confirmed excision may be preferable; 4) traumatic neuroma pain is only partly due to a peripheral source; 5) demographic and neurological variables do not predict success; 6) the presence of a discrete nerve syndrome and mechanical hyperalgesia modestly predict pain relief; 7) ongoing litigation is the strongest predictor of failure; and 8) change in work status is not a likely outcome. PMID- 8468602 TI - Repair of facial nerve after removal of cerebellopontine angle tumors: a comparative study. AB - The results of repair of 18 facial nerves were examined by means of a modified House-Brackmann grading system. Six were repaired by end-to-end anastomosis and 12 by nerve graft. The reliability of the simplified House-Brackmann grading system was also assessed, using the kappa statistic to analyze the agreement between pairs of observers who examined the function of 40 nerves in 37 patients. Facial nerves studied had been either preserved, repaired or grafted, or divided and treated by faciohypoglossal nerve anastomosis. One nerve was not treated. The grading system proved to be somewhat unreliable, with complete agreement between observers in only 25% of cases. Facial nerve repair produced a fair return of function in just under two-thirds of the cases. The ability of an examiner ignorant of the patient's history to assess from the end result how the nerve had been managed was also estimated. Observers showed little ability to decide correctly on the previous treatment of the nerve when the patient showed moderate dysfunction postoperatively. The implications of these findings for grading systems and for management of the facial nerve in acoustic nerve tumor surgery are discussed. PMID- 8468603 TI - Referral bias in aneurysmal subarachnoid hemorrhage. AB - The objective of this study was to assess the effect of referral bias on survival in patients with subarachnoid hemorrhage (SAH). The characteristics of 49 patients with aneurysmal SAH from a single community were compared with those of 328 patients referred from outside the community, all treated in the same medical care setting. In addition, referral patients who received surgery were compared by differential survival analysis with those still awaiting surgery at Days 1 to 3, Days 4 to 10, and Days 11 to 15. There was a dramatic difference in the 30-day survival rate between referral patients (83%) and community patients (59%), but most of the difference had occurred by the 2nd day after SAH. In the referral patients, the variables present at first medical attention that were found to have an independent effect on survival were clinical grade, presence of coma, number of days from SAH to referral, diastolic blood pressure, and patient age. There was a higher survival rate at 1 year for patients who were surgically treated compared with those awaiting surgery for each of the three time periods. Patients who underwent early surgical treatment had a 1-year survival rate almost identical to that of patients with late surgery. Referral patients had a better early survival rate than did community patients because the referral group did not include patients who died and some who were in poor clinical condition before the opportunity for referral. The differential survival analysis described provides a new method for estimating survival for treated and untreated patients with SAH. PMID- 8468604 TI - Hemispherectomy for intractable seizures: long-term results in 17 patients followed for up to 38 years. AB - Seventeen patients who underwent hemispherectomy for intractable epilepsy between 1950 and 1971 were reviewed to evaluate outcome for seizure control and the development of late complications. Sixteen had complete resection and in one the frontal pole was preserved. The follow-up period was 19 to 38 years (mean 28 years). One patient was lost to follow-up review 10 years after surgery. Three patients had died but none of the deaths were related to the surgery or to epilepsy. Ten patients had no postoperative complications, and three developed late complications: two had elevated intracranial pressure with enlargement of the remaining lateral ventricle after 13 and 16 years, and one had recurrent bleeding into the cerebrospinal fluid after 6 years. All were treated surgically and have since remained well. Eight patients (47%) had no seizures after surgery and eight (47%) were almost seizure-free. It is concluded that classical hemispherectomy is an effective operation for control of some types of epilepsy. The late complications, which occurred in 17% of the cases in this series, can be successfully treated. This series presents the longest follow-up results after hemispherectomy reported to date. PMID- 8468605 TI - Intracranial chordomas: a clinicopathological and prognostic study of 51 cases. AB - Fifty-one patients with intracranial chordomas who were surgically treated between 1960 and 1984 were studied. Median patient age was 46 years, and 73% presented with diplopia or headache. Nineteen tumors were classified as the "chondroid" type. The extent of surgical removal was a biopsy in 11 patients and subtotal removal or greater in 40. Thirty-nine patients received postoperative radiation therapy. At the time of analysis, 17 patients were alive, and the estimated 5- and 10-year survival rates were 51% and 35%, respectively, for the group of 51 patients. Univariate analysis showed that: 1) patients undergoing resection lived longer (the 5-year survival rate was 36% for the 11 biopsy patients compared with 55% for the 40 patients who had resection; 2) patients who underwent postoperative radiotherapy tended to have longer disease-free survival times; and 3) overall and disease-free survival data were the same for patients with chondroid tumors and those with typical chordomas. Multivariate analysis showed that: 1) age was the factor most strongly associated with longer overall and disease-free survival; 2) diplopia was associated with longer survival; and 3) tumoral mitotic activity tended to be associated with shorter disease-free survival. One tumor metastasized to the cervical cord, and two tumors underwent anaplastic transformation. These data suggest that the prognosis in patients with chordomas is unfavorable, young age is the single factor most strongly associated with longer survival, surgical resection is beneficial, and postoperative radiotherapy may prolong disease-free survival. PMID- 8468606 TI - High recurrence rate following aspiration of colloid cysts in the third ventricle. AB - Sixteen patients treated between 1969 and 1989 for a colloid cyst of the foramen of Monro by stereotactically guided aspiration (not stereotactic extirpation) were evaluated to assess the long-term outcome of the procedure. Thirteen of these patients required reoperation due to an acute comatose state, failure to achieve permanent reduction of the cyst, or symptomatic hydrocephalus. Of these 13, six were treated twice and two were treated three times by stereotactic aspiration. Five patients underwent microsurgical extirpation and three had a shunt placed following a failed aspiration. Failure of the first procedure was detected within the first 2 months after treatment in eight patients and after more than 6 years in seven. Following stereotactic aspiration, three patients experienced a temporary memory deficit and confusion and one patient suffered a central pain syndrome. Eleven of the 26 procedures were followed by a recurrence 6 to 15 years after treatment; seven recurrent cysts were detected after more than 8 years. Of the patients with recurrences, three did not undergo repeat surgery but showed an increase in cyst size at the latest follow-up examination. It is suggested that radical removal by open or stereotactically guided microsurgery is the method of choice since stereotactic aspiration fails to offer a radical or permanent treatment for colloid cysts of the third ventricle. PMID- 8468607 TI - Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. AB - Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone. PMID- 8468608 TI - Comparative study of transcranial color duplex sonography and transcranial Doppler sonography in adults. AB - To determine whether the frequency shift recorded in basal cerebral arteries corresponds to "true" flow velocities, a prospective comparative study of transcranial color duplex sonography (TCCD) and transcranial Doppler sonography (TCD) was performed. A 2.0-MHz transducer of a computerized TCCD system and a TCD device were used. The middle cerebral artery (MCA) and anterior cerebral artery (ACA) were examined by TCCD in 49 healthy volunteers (mean age 35 +/- 12 years). In 45 of the same volunteers a comparative TCD examination was possible. The studies were carried out blindly by different examiners at separate appointments. Peak systolic flow velocity, end-diastolic maximum flow velocity, time-averaged maximum flow velocity, and the pulsatility index were measured by both techniques. Additionally, for TCCD, time-averaged flow velocity was assessed, the resistance index and a spectral broadening index were calculated, and the energy output required for reliable measurement was analyzed. The TCCD signals were recorded in 98% of both MCA's and ACA's; with TCD, signals were recorded in 98% of MCA's and 87% of ACA's. Although in both vessels the angle-corrected peak systolic and time-averaged maximum velocities were approximately 10% to 15% higher in TCCD than in TCD measurements, correlation of flow velocities between both techniques was significant (p < 0.0001); differences between sides and age dependency of flow velocities corresponded as well. In a reproducibility study, TCCD was repeated in 27 subjects by a third examiner with significant correlation (p < 0.0001) of both TCCD examinations. It is concluded that the advantage of TCCD is associated more with a qualitative aspect than a quantitative one. The additional visual dimension of TCCD can open new diagnostic possibilities in cerebrovascular disorders. PMID- 8468609 TI - Optical imaging of bipolar cortical stimulation. AB - In order to better understand the degree of cortical activation that occurs during bipolar surface stimulation, the authors stimulated monkey visual cortex while monitoring the degree of activation with optical imaging. Optical imaging of intrinsic signals in monkey visual cortex during visual stimulation resulted in functional maps of ocular dominance and orientation selectivity. After functional maps of ocular dominance and orientation preference were obtained, bipolar surface stimulation was applied to activate just the cortical areas around the bipolar electrodes. Graded responses to changes in the stimulation intensity and duration were found. These findings demonstrate the reliability of bipolar cortical surface stimulation in localizing functional regions of cortex. The area of activation, at least in the region around the bipolar stimulating electrodes, did not appear to activate nearby ocular dominance columns or orientation patches. Intraoperative bipolar surface stimulation continues to be a consistently reliable technique for localizing rolandic cortex and essential language sites. PMID- 8468610 TI - Observations on the blood and perineurial permeability barriers of surviving nerve allografts in immunodeficient and immunosuppressed rats. AB - The authors investigate whether there are any permeability changes in the endoneurial blood-nerve barrier and the perineurium-nerve barrier of surviving nerve allografts. In a normal nerve, the blood-nerve barrier regulates the passage of substances from endoneurial blood vessels into the endoneurium, whereas the perineurium-nerve barrier protects the endoneurium from agents that escape from permeable epineurial vessels and accumulate around the nerve. Nerves from ACI rats were transplanted into immunologically deficient nude rats or normal Fischer rats immunosuppressed with cyclosporin A. None of the nerve allografts was rejected. The blood-nerve barrier of nerve allografts at 2 and 6 weeks postoperatively was permeable to intravenously injected horseradish peroxidase, which spread into endoneurial tissue. Electron microscopy revealed that horseradish peroxidase escaped from endoneurial vessels through intercellular junctions between endothelial cells. At 24 weeks, the blood-nerve barrier of nerve allografts had recovered and the endoneurial vessels, like those in normal nerves, were impermeable to horseradish peroxidase. The perineurium nerve barrier of nerve allografts remained impermeable to horseradish peroxidase at all times. Axons were grouped into numerous minifascicles at nerve anastomosis zones at 24 weeks. Each nerve fascicle was surrounded by an impermeable perineurium. These results demonstrate that regenerated axons in long-term surviving nerve allografts and at anastomosis zones are protected by permeability barriers. It is concluded that permeability barriers of nerve allografts are not permanently altered by a foreign environment (grafts to nude rats) even when immunosuppression with cyclosporin A is required to prevent allograft rejection (grafts to Fischer rats). PMID- 8468611 TI - Temporal profile and significance of metabolic failure and trophic changes in the canine cerebral arteries during chronic vasospasm after subarachnoid hemorrhage. AB - To investigate the pathogenetic significance of metabolic failure observed in spastic cerebral arteries after subarachnoid hemorrhage (SAH), the temporal profile of alterations in the arterial content of high-energy phosphates was studied. A canine model of double hemorrhage was used. Constriction of the basilar artery was measured angiographically on Days 3, 5, 7, and 14 after SAH in separate groups of animals. Adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), guanosine triphosphate (GTP), guanosine diphosphate, creatine phosphate (CrP), and creatine (Cr) levels in the arteries were assayed using high-performance liquid chromatography. A time-dependent development of angiographic spasm was confirmed. A mild vasospasm was seen in the group studied 3 days after SAH, progressed in the Day 5 group, remained comparably severe in the Day 7 group, and resolved partially in the Day 14 group. The content of high-energy phosphates (ATP, GTP, and CrP) declined rapidly over the course of the study, and a significant reduction in ATP, GTP, and CrP was observed in the Day 3 group. Levels of ATP and CrP decreased further in the Day 5 and 7 groups. The decrement in GTP was completed in the early phase; a significant reduction took place in the Day 3 group, with no progression thereafter and no recovery through Day 14. Total adenylate (ATP + ADP + AMP) and total creatine (Cr + CrP) content diminished markedly over the course of the study. These results indicate that metabolic failure and trophic disturbance in the cerebral artery occurs with a rapid onset following SAH and progresses in close association with the development of vasospasm, suggesting a significant causal relationship with the pathogenesis. PMID- 8468612 TI - Intractable hiccups: treatment by microvascular decompression of the vagus nerve. Case Report. AB - Idiopathic hiccups are usually managed with pharyngeal stimulation or a plethora of pharmacological agents. Hiccups that persist and prove intractable to these medical measures are treated by crush or ablation of the phrenic nerve, which denervates the major respiratory muscle. This is the first reported case of nondestructive microvascular decompression of the vagus nerve for the treatment of intractable idiopathic hiccups. The success of microvascular decompression has been documented with other conditions, such as trigeminal neuralgia and hemifacial spasm, that are characterized by hyperactive dysfunctional neurovascular contact. The vagus nerve was separated from the posterior inferior cerebellar artery by inserting a Teflon pledget between the nerve and vessel which eliminated the neurovascular contact. One year after the initial surgery, the hiccups recurred. The Teflon pledget had fallen out of place and the nerve was once again in contact with the artery. Once the contact was eliminated by wrapping the artery with a tuft of Teflon, the hiccups stopped. The patient has remained free of hiccups for 3 years. It is concluded that patients with intractable idiopathic hiccups who fail medical therapy should be considered for microvascular decompression of the vagus nerve. PMID- 8468613 TI - Bovine thrombin-induced inhibitor of factor V and bleeding risk in postoperative neurosurgical patients. Report of three cases. AB - Three patients are reported who developed topical bovine thrombin-induced antibodies to clotting factor V following neurosurgical procedures. In each patient the coagulopathy occurred within 8 to 13 days following exposure to topical bovine thrombin at surgery. Two of the three had previously been exposed to bovine thrombin during cardiothoracic surgery. The three patients were identified by detection of a prolonged prothrombin time, ranging from 20.5 to 39.8 seconds. The patient with the highest factor V level (0.12 U/ml) experienced gastrointestinal bleeding, which ceased when the factor V level increased to more than 0.20 U/ml. One patient required a ventriculostomy. In that case the prothrombin time and factor V level failed to improve following administration of vitamin K, 10 units of fresh frozen plasma, and platelet transfusions; the factor V level temporarily increased from 0.03 to 0.32 U/ml following a 2-day course of intravenous gamma globulin (1 gm/kg/day). Plasmapheresis has also been reported to be transient benefit in the treatment of this coagulopathy. In most patients the factor V level rises and the prothrombin time improves toward normal within 3 to 6 weeks following surgical exposure. The individuals identified likely represent only a fraction of the patients who develop the coagulopathy. The latter either do not bleed or are not sufficiently challenged in the postoperative period for the bleeding risk to be tested. It is concluded that bovine thrombin-induced coagulopathy may occur following surgical exposure to topical bovine thrombin and may result in both postoperative morbidity and mortality in a subset of patients. PMID- 8468614 TI - Lumbosacral neurenteric cyst in an infant. Case report. AB - The case of a combined intra- and extraspinal neurenteric cyst in an infant is reported. This case is unique because an intraspinal cyst was not suspected clinically until large numbers of squamous epithelial cells were obtained at lumbar puncture performed as part of a workup for a septic entity. The cyst extended from an intradural location ventral to the conus medullaris at L-1 through a ventrolateral defect in the S-4 vertebral body to communicate with a large presacral component. The entire cystic cavity was lined by stratified squamous epithelium. The possible pathogenesis of this lesion is discussed. PMID- 8468615 TI - Acute obstructive hydrocephalus caused by a migrating intraventricular calculus. Case report. AB - A 10-year-old boy presented with acute obstructive hydrocephalus caused by the impaction of a calculus on the cerebral aqueduct. The calculus migrated from the third ventricle to the fourth ventricle after ventricular drainage and right ventriculoperitoneal shunt placement had been performed. The nature and origin of the calculus could not be determined, although its release from the choroid plexus in the lateral ventricle is highly possible. PMID- 8468616 TI - Encapsulated intracerebral hematomas: a defined entity. Case report. AB - Encapsulated intracerebral hematoma is an interesting and not widely appreciated entity. It can be defined as an intraparenchymal hematoma found in normotensive patients, usually caused by histologically confirmed vascular malformations, characterized by a gradual clinical onset, and presenting a well-defined capsule at operation. One case is presented and 25 previously reported cases are reviewed, all reflecting the above-mentioned characteristics. The hematomas reviewed here occurred in relatively young patients with a mean age of 35 years and a clear male predominance (19 males, seven females). A ring of contrast enhancement around a lesion of variable density, usually with mass effect and perifocal edema, is the most relevant feature on computerized tomography. Findings on magnetic resonance images are described for the first time in the reported case. A vascular malformation was the most frequent cause found on histological examination (12 of the 26 total cases). No proven cause was found in the remaining 14 cases, although a small vascular malformation, destroyed or thrombosed after rupturing and bleeding, is the most likely etiology in these patients. PMID- 8468617 TI - Improved transdural exposure and temporary occlusion of the petrous internal carotid artery for cavernous sinus surgery. Technical note. AB - Safe surgery for vascular and neoplastic lesions involving the cavernous sinus requires adequate proximal control of the cavernous internal carotid artery (ICA). Classically, control of the cavernous ICA has necessitated dissection and isolation of the cervical vessels. The authors describe an alternative method for obtaining vascular control via transdural exposure of the petrous ICA and the use of the Fogarty balloon embolectomy catheter inserted extra-arterially into the carotid canal to provide temporary occlusion. This method is particularly well suited for proximal ICA occlusion during short-segment petrous-to-paraclinoid ICA bypass procedures as it eliminates the need for a temporary proximal ICA aneurysm clip and increases the available working space for completion of the anastomosis. PMID- 8468618 TI - Treatment of head injuries in the American Civil War. AB - At the time of the American Civil War (1861-1865), a great deal was known about closed head injury and gunshot wounds to the head. Compression was differentiated from concussion, but localization of lesions was not precise. Ether and especially chloroform were used to provide anesthesia. Failure to understand how to prevent infection discouraged physicians from aggressive surgery. Manuals written to educate inexperienced doctors at the onset of the war provide an overview of the advice given by senior surgeons. The Union experiences in the treatment of head injury in the Civil War were discussed in the three surgical volumes of The Medical and Surgical History of the War of the Rebellion. Wounds were divided into incised and puncture wounds, blunt injuries, and gunshot wounds, which were analyzed separately. Because the patients were not stratified by severity of injury and because there was no neuroimaging, it is difficult to understand the clinical problems and the effectiveness of surgery. Almost immediately after the war, increased knowledge about cerebral localization and the development of antisepsis (and then asepsis) permitted the development of modern neurosurgery. PMID- 8468619 TI - Perfusion pressure and risk of AVM hemorrhage. PMID- 8468620 TI - Cervical spondyloptosis. PMID- 8468622 TI - Distal catheter lengthening. PMID- 8468621 TI - Distal catheter lengthening. PMID- 8468623 TI - Knowledge-based design of removable partial dentures using direct manipulation and critiquing. AB - A knowledge-based system for designing removable partial dentures is described in which graphical representations of denture components are manipulated directly by the user to build the required denture design. The arch form of individual patients may be depicted by linear movement and rotation of the icons representing teeth. The size, shape and position of many denture components are determined dynamically to conform to the shape of abutment teeth and to the juxtaposition of other elements. Expert clinical knowledge is used to analyse the developing design and suggest alternate approaches. PMID- 8468624 TI - A system for assessing the severity and progression of occlusal tooth wear. AB - This study represents an attempt to introduce a system for the longitudinal evaluation of the severity and the rate of progression of tooth wear. The material comprised a selected group of 10 males and 10 females, examined twice within an 18-month period. The subjects were predisposed to advanced occlusal wear and had a mean age of 32 years within the range of 16-56 years. Evaluation of occlusal wear was performed on a tooth-by-tooth basis, on study casts, using two ordinal scales, one for assessing the severity, and the other the progression of occlusal wear. The reliability of the scales was assessed by percentage inter observer concordances. The sample exhibited higher occlusal wear scores in the incisor and canine regions compared to the posterior region. It was found that the overall progression in an 18-month follow-up period was slow. The inter observer concordance in the evaluation of the severity of wear was 88%, and 91% in the progression of wear. Within the limitations of the described system, the scales may be utilized for determining the severity of occlusal wear and the rate of its deterioration in an individual's dentition. From a clinical standpoint, the need for future treatment may be based on such a evaluation of the progression of wear. PMID- 8468625 TI - Dual-cure luting composites: Part I: Filler particle distribution. AB - Fourteen dual-cure luting composites were analyzed for their filler particle shape, predominant and maximum filler size, and filler weight in function of their clinical use. Polished surfaces were etched with an argon ion beam and studied by means of scanning electron microscopy. The type of filler particles, either inorganic or prepolymerized, could clearly be recognized. Their shapes were angular, rounded or spherical, depending on the product. The maximum filler size varied extremely from less than 1 micron to 250 microns. A particle-size distribution analyser disclosed a bell-shaped filler-size distribution. The predominant filler size for all the products was much smaller than the maximum filler size. The filler weight varied from 36 to 77%. After ion etching, some products showed small areas with a low degree of filler loading. A classification of the luting composites based on the maximum filler size is proposed. Since the particle size varies widely within the group of products analyzed, a standard specification for luting composites is urgently needed. PMID- 8468626 TI - A comparison of three finite element models of an edentulous mandible provided with implants. AB - The stress distribution in an edentulous mandible provided with two implants in the interforaminal region was calculated by means of three different finite element models. The implants were connected with a bar or remained solitary. The first model was a three-dimensional representation of the entire mandible, the second model of the interforaminal region of this same mandible, whilst the third model was a two-dimensional representation of the interforaminal region. The differences in stress distribution around the connected implants and the solitary implants between these three models were analysed. It can be concluded that for a parameter study the stress distribution around the dental implants following from a three-dimensional finite element model of only the interforaminal region of an edentulous mandible can be used. For such studies therefore, benefit can be gained from the advantages of reduced modelling and calculation time. PMID- 8468627 TI - Comminution of two artificial test foods by dentate and edentulous subjects. AB - An experimental artificial test food with low fracture strength (Optocal) was compared with Optosil with respect to the comminution during mastication by complete denture wearers and subjects with natural dentitions. The comminution of both test foods revealed large differences between the denture wearers and the dentate subjects. These differences were larger with Optosil than with Optocal. The differences in comminution between Optocal and Optosil were larger in the denture wearers than in the dentate subjects. The differences in comminution between the denture wearers and the dentate subjects as well as the differences in comminution between Optocal and Optosil within each group were largely established in less than 20 chewing strokes. The results indicate that differences in selection contributed substantially to the differences in comminution. Since Optocal appeared to be much easier to chew than Optosil, it may be preferred to Optosil for measuring masticatory performance in complete denture wearers. PMID- 8468629 TI - Parameters of tooth mobility in cases of normal function and functional disorders of the masticatory system. AB - Tooth mobility was measured mechano-electronically with the aid of quasi-static and dynamic methods in 309 patients comprising 2650 teeth being periodontally healthy. Besides, clinical and roentgenographic findings were ascertained to relate functional features to each periodontium. In general the result was that teeth loaded excessively show increased mobility parameters compared to those loaded normally. However, the mobility of teeth loaded poorly or deficiently was even greater compared to teeth stressed excessively. Moreover, follow-up studies showed that tooth mobility decreases after removal of functional disorders of the masticatory system or an immobilisation of splinted teeth. An experimental trauma of the periodontal ligament also brings on an increased tooth mobility which decreases to the original values some days after the trial. PMID- 8468628 TI - Initial flow of tissue conditioners--influence of composition and structure on gelation. AB - The effects of the molecular weight of polymer powders, the ethyl alcohol content of the liquids, the type of plasticizer and the polymer powder/liquid ratio on viscoelastic properties during gelation of tissue conditioners were studied with an oscillating rheometer. The results showed that: (i) The gelation time decreased exponentially with increases in molecular weight of the polymer powder and with powder/liquid ratio. There were linear relationships between the log of gelation time, and both the molecular weight of the polymer powder and the powder/liquid ratio. (ii) In general, gelation time decreased exponentially with increases in ethyl alcohol content. However, the relationship between the log of the gelation time and ethyl alcohol content fitted a second-order polynomial. (iii) The type of plasticizer affected gelation time. The order of gelation times was: benzyl benzoate < dibutyl phthalate < butyl phthalyl butyl glycolate. The initial flow of tissue conditioners could be controlled over a wide range by varying the molecular weight of the polymer powders, the ethyl alcohol content, the powder/liquid ratio and the type of plasticizer. PMID- 8468630 TI - Longitudinal study on torque around the sagittal axis in lower distal-extension removable partial dentures. AB - The purpose of this study was to examine the longitudinal changes of torque around the sagittal axis in lower distal-extension removable partial dentures. The torque transmitted from the denture base to retainers was measured on several separate occasions from the insertion of new dentures to about 2 months after it. The maximal mean value of torque (Max.MT) was calculated from the magnitude of all chewing strokes of the minimum of the interocclusal distance. The integration values of torque (I) and time (T) from initiation of chewing to swallowing were obtained and then the average value of torque (Ave.T) was calculated (Ave.T = I/T). Subjects could be divided into two groups. Max.MT and Ave.T were almost constant in one group while they were remarkably decreased in another. After 1 month of insertion of new dentures the value of both groups was within the range of less than 3 x 10(-3) kgm (1 kgm = 9.8 Nm) of Max.MT and less than 1 x 10(-3) kgm ss-1 of Ave.T. PMID- 8468631 TI - Enamel surface roughness analysis after laser ablation and acid-etching. AB - Laser-roughened enamel surfaces have been shown to provide for greater acid resistance and enhanced restorative material/enamel bond strength. Extracted tooth enamel was irradiated with several lasers: CO2/Nd:YAG (CW), CO2 (RSP), Nd:YAG (CW), Nd:YAG (Q-switched), Argon (CW), and Ar:F excimer. Additional teeth were acid-etched. Energy densities were standardized at 25.47 J/cm2 for all mediums. Surface profile analyses were conducted with a profilometer to determine the amount of enamel surface roughness. The acid-etched samples exhibited both a greater amount of surface roughness and a qualitatively different type of enamel surface morphology than the laser-treated specimens. Independent use of the CO2 and Nd:YAG beams exhibited a moderate amount of roughness, while the coaxial CO2/Nd:YAG beam displayed surface roughness approaching that of the acid-etch samples. Different laser mediums produce enamel surface morphologies that are characteristic of a variety of inherent lasing parameters. PMID- 8468632 TI - A method for the estimation of traces of chlorhexidine in water. AB - A simple method of estimating traces of chlorhexidine in water using bromothymol blue is described. The procedure involves the extraction of the chlorhexidine/bromothymol blue complex into carbon tetrachloride from a buffered neutral solution and measurement of the absorbances of the extracts in a spectrophotometer. The extracted complex has good colour stability, and the method is accurate, reproducible, and very sensitive, with concentrations of chlorhexidine down to 0.05 micrograms ml-1 measurable. PMID- 8468633 TI - Geometrical interpretation for abnormal facial behaviour with possible correction of angle S-N-A and S-N-B. AB - The orientation of the sella nasion (SN) line in lateral skull radiographs is important for accurate assessment of antero-posterior and vertical facial relationship. Lateral skull radiographs of a random sample were traced and digitized to produce a mean shape template of the sample, with the craniofacial centroid line (CFC) used as a base for superimposition of the sample. A geometrical triangle was formed using the sella nasion line, craniofacial centroid line and the mandibular plane as the sides of the triangle. Simple geometric calculations were done to re-orient both the mandibular plane and sella nasion line in cases with balanced clinical profiles, while the S-N-A and S-N-B measurements indicate otherwise. PMID- 8468634 TI - Health care costs in a declining America. PMID- 8468635 TI - Intestinal transplantation in the child: experimental and clinical studies. PMID- 8468636 TI - Efficacy of pediatric trauma care: results of a population-based study. AB - To determine concordance between regional outcome and national norms with respect to pediatric injury diagnosis, severity, and mortality in a state lacking a well organized trauma system, we compared summary data from all pediatric trauma related hospital discharge abstracts compiled by the [New York State Department of Health] Statewide Planning and Research Cooperative [Mandatory Hospital Reporting] System (SPARCS), with comparable data from pediatric trauma centers participating in the National Pediatric Trauma Registry (NPTR), for similar epochs in the late 1980s. Analysis was based on 14,234 cases from SPARCS and 17,098 cases from NPTR. Data were grouped by principal anatomic diagnosis (ICD-9 CM N-code) and injury severity score (ISS), for each of which incidence and mortality were calculated, both individually and collectively, then compared item by item for sources of variance. Overall, the two data sets showed the expected discordance, with NPTR being skewed toward more complex and severe injury. However, when analyzed cell by cell, a striking degree of concordance emerged in both incidence and mortality for injuries of comparable severity in all but a few selected subsets. Isolated skeletal injuries were treated less frequently in pediatric trauma centers, and combined system injuries to the skeleton, brain, and internal organs were treated more frequently in pediatric trauma centers. However, while the fatality rates were similar between SPARCS and NPTR for most diagnoses, given comparable ISS, survival was some ten times greater in pediatric trauma centers for patients with either brain or internal injuries--the leading causes of pediatric injury mortality--and for skeletal injuries, when the injuries sustained were of moderately great severity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468637 TI - Does handgun legislation change firearm fatalities? AB - When comparing firearm fatalities for children under 16 years of age before and after handgun legislation enactment in Maryland, firearm fatalities increased overall. A decrease in accidental deaths in the home perhaps reflects a response to public education and awareness. More aggressive handgun legislation is imperative to reverse this public health trend. PMID- 8468638 TI - The effect of hypotension and hypoxia on children with severe head injuries. AB - Survival of children (< 17 years) with severe head injuries (Glascow Coma Scale [GCS] score < 8) has been shown to be better than that of adults. The addition of hypotension (HT) or hypoxia (H) has a deleterious effect on outcome in adults but no information is currently available about their effects in children. Over a 5 year period, 58 children with GCS scores < 8 were admitted and prospectively evaluated at this institution. Patients were divided into two groups on the basis of systolic blood pressure (SBP) and arterial blood gasses. Patients exhibiting HT, defined as a SBP < 90 mm Hg, and patients demonstrating H with a PaO2 < 60 mm Hg were compared with normoxic, normotensive children. Survival was increased fourfold in patients with neither H nor HT as compared with children with either H or HT (P < .001). To validate these observations we reviewed the data from the National Pediatric Trauma Registry for similar patients and included our cohort in the analysis. In total, 509 children had sufficient data for analysis and were studied. Hypoxia alone was not associated with increased mortality in normotensive patients (P = .34). Hypotension significantly increased mortality in these children even without concomitant H (P < .00001). If both HT and H were found together, mortality was only slightly increased over those children with HT alone (P = .056). These data confirm that HT with or without H causes significantly increased mortality in head-injured children to those levels normally found in adults (P = .9), alleviating any age-related protective mechanisms normally afforded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468639 TI - Successful repair of major retrohepatic vascular injuries without the use of shunt or sternotomy. AB - Injury to the retrohepatic veins and vena cava secondary to blunt abdominal trauma is often fatal. The purpose of this report is to describe the successful isolation and repair of retrohepatic vascular injuries without the use of median sternotomy or vena caval shunt. Two children with both hepatic vein and retrohepatic caval injuries from blunt trauma were treated by the following surgical approach: (1) bilateral subcostal incision with vertical midline extension; (2) packing of the liver and volume resuscitation with the Rapid Infusion System prior to vascular isolation; (3) isolation of the intrapericardial vena cava through a transdiaphragmatic pericardial window; (4) control of the suprarenal vena cava and porta hepatis; and (5) repair of vein lacerations with vascular occlusion and continuous saline irrigation for improved visualization despite continued venous bleeding. This approach was tolerated and allowed successful repair without shunting in these patients despite an average weight of 14 kg and the loss of 3 L and 23 L of blood, respectively. We attribute the success of this technique to rapid control of hemorrhage and volume resuscitation. This success suggests that the routine use of shunt or sternotomy is not necessary in these devastating injuries. PMID- 8468640 TI - Does the current health care environment contribute to increased morbidity and mortality of acute appendicitis in children? AB - To determine whether the current "gatekeeper" controls on health care lead to an increase in treatment delay and morbidity of acute appendicitis in children, we reviewed the experience with this disease at a large children's hospital over a 10-year period. One hundred seven consecutive children 18 years and younger operated on for acute appendicitis from July 1, 1988 to June 30, 1990 were compared with 119 children with the same diagnosis from July 1, 1978 to June 30, 1980. Age, sex, race, antecedent illnesses, initial physician contact and diagnosis, time to referral and operation, pathology, morbidity, and length of stay were reviewed. The two groups were comparable in terms of age, sex, race, antecedent illnesses, and negative appendectomy rate. More patients in the recent group were initially seen in an emergency room or urgent care setting than in the previous group (62.2% v 48.5%, P = .07). The accuracy of the initial diagnosis was significantly lower in the more recent group (P = .05). No change existed between the groups in the time to a physician; however, a significant (P = .04) difference existed in the time to surgeon (41.2 hours in the earlier group v 56.4 hours in the recent group). No significant difference existed between the groups in time from surgeon to operation. Although not statistically significant, the morbidity rate was increased in the recent group (13.3% v 6.5%, P = .17).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468641 TI - Blood clearance and organ localization of Candida albicans and E coli following dual infection in rats. AB - Immunosuppressed prematures, cancer patients, and transplant recipients are susceptible to bacterial or fungal sepsis or both. This report evaluates whether the ability of the reticuloendothelial system (RES) to remove blood-borne viable radiolabeled 35S Escherichia coli and 3H-Leucine Candida albicans is adversely affected by a dual intravenous challenge of these organisms. Male Sprague Dawley rats (n = 150) weighing 175 to 180 g were placed in 5 experimental groups (n = 30). Group I received intravenous (IV) C albicans (10(7)/mL), group II received E coli (10(9)/mL), group III received a dual injection of C albicans and E coli, group IV received Candida 1 hour prior to E coli, and group V received E coli 1 hour prior to fungi. At 1, 4, and 24 hours, tissue samples (50 to 100 mg) of liver, spleen, kidneys, and lungs were processed for liquid scintillation counting. Organ distribution of bacteria and fungi was calculated and expressed as mean percent +/- SD of labeled organisms. The liver trapped 72% +/- 10% and the lungs 1.1% +/- 0.3% of E coli (group II) (P < .001). The organ distribution of Candida (group I), however, was similar in liver and lungs (42.5% +/- 10% and 41.4% +/- 6.4%, respectively). Liver localization of E coli was unaffected by simultaneous or staggered fungal injection (groups III, 4, and V). Lung distribution of E coli following dual injection (group III) was significantly higher than controls (group II) (3.6% +/- 0.7% v 1.1% +/- 0.3%; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468642 TI - The effect of endotoxin on the neonatal erythrocyte. AB - Intestinal ischemia is considered a major factor in the development of necrotizing enterocolitis (NEC). Despite this, the majority of affected infants lack documentation of clinical events associated with obvious gut hypoperfusion. Recent evidence in adults suggests that endotoxin may impair flow in the microcirculation through alterations in erythrocyte deformability. As the gut serves as a semipermeable reservoir of endotoxin in the stressed neonate, such localized activity may result in intestinal ischemia at the microcirculatory level through alterations in the red cell membrane. This study evaluates the role of endotoxin on neonatal erythrocyte membrane viscosity. Paired anticoagulated whole blood specimens were obtained from the umbilical cord of 10 neonates at delivery. Samples were incubated with either 2 micrograms/mL of E coli endotoxin (LPS) or an equal volume of saline (control). Following incubation, erythrocytes were isolated, washed, and incorporated with the fluorescent membrane probe TMA DPH. Membrane viscosity was assessed by spectroscopic analysis of the fluorescent emissions induced by excitation of the probe at 365 nm. Results were calculated as anisotropy and analyzed for differences by ANOVA. Endotoxin resulted in a significant increase in red cell membrane viscosity as compared to control (LPS 291.2 +/- 5.1 v Control 271.7 +/- 3.3, P < .01). As the effects of endotoxin are known to be primarily the result of white blood cell (WBC) activation, this study was repeated in an additional 10 neonates in whom WBCs were removed prior to endotoxin/saline incubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468643 TI - Nosocomial infection in pediatric surgical patients: a study of 608 infants and children. AB - We studied nosocomial infection in a group of 608 pediatric surgical patients over a 14-month period. All inpatients and outpatients who received an operation with an incision by the pediatric general surgical service were entered into the study. Demographic, nutritional, clinical, and laboratory data were collected. Surveillance was conducted for wound infection, septicemia, infections of the respiratory tract, urinary tract, and abdomen, and infectious diarrhea. A total of 676 operative procedures was performed. Nosocomial infection occurred in 38 of the 608 patients (6.2%). A total of 53 infectious complications was tabulated. The number and percent risk per operation were wound 17 (2.5%), septicemia 14 (2.1%), pulmonary 10 (1.5%), urinary tract 5 (0.7%), abdominal 5 (0.7%), diarrhea 2 (0.3%). Broviac catheter sepsis occurred in 7 of 61 lines (11.5%). The highest overall occurrence of infection was in the infant group (1 mo to 1 yr), (13/161, 8.1%). The probability of septicemia was highest in neonates (4.2%) compared with infants (3.1%) or older children (1.2%) (P < .05). The most common isolates were Staphylococcus epidermidis (10/17) from septic patients, and gram-negative enteric bacteria (27/50) from organ and wound infections. Infection was associated with impaired nutrition, multiple disease processes, and multiple operations. The risk of nosocomial infection in this population was comparable to that reported in adult surgical patients. These baseline data may aid the development of strategies to lower infection risk in children. PMID- 8468644 TI - Does the fibrin coat around a central venous catheter influence catheter-related sepsis? AB - The purpose of this study was to determine whether the fibrin sheath that develops around an intravenous silicone catheter influences catheter-related sepsis. A rat model with a central intravenous silicone catheter was used. Staphylococcus aureus, dose 1 x 10(7) colony forming units (cfu), were injected via the tail vein, either immediately after catheter insertion (group 1, n = 23) or after the catheter had been in situ for at least 7 days (group 2, n = 22). Blood cultures were done on at 24 hours and 7 days. Animals were killed on day 7 and the catheter was removed for culture (Maki and broth) and scanning electronmicroscopy (SEM). The was no significant difference (P > .05) between the number of positive blood cultures in groups 1 and 2 at 24 hours (16 v 9) and 7 days (12 v 6). In group 1 there were significantly more positive catheter cultures by both methods (23 v 16 in group 2; P < .05) and more cfu/per centimeter catheter (group 1 mean, 520, range, 197 to 600; group 2 mean 195, range 9 to 600; P < .001). In group 1, 12 animals had catheter sepsis compared with 5 in group 2 (P = NS). On SEM a fibrinous sheath was identified on all catheters removed on day 7 but not on 5 catheters inserted and removed after 10 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468645 TI - Prospective analysis of urokinase in the treatment of catheter sepsis in pediatric hematology-oncology patients. AB - Use of right atrial catheters (RACs) in children with cancer improves the comfort and efficacy of therapy. However, catheter-related infections are responsible for significant morbidity leading to the removal of approximately 20% of implanted RACs. Sepsis has been linked to thrombus and fibrin sheath formation within the RAC. Gram-negative and fungal infections appear to be particularly resistant to antibiotic therapy alone and most of these infections have required catheter removal. Urokinase has been effectively used for reopening thrombus occluded RACs. Theoretically, thrombolytic agents could improve the treatment of catheter related infections by removing luminal sites of bacterial/fungal colonization. We prospectively monitored the use of urokinase and antibiotics for catheter-related sepsis in our pediatric hematology/oncology population from 1985 to 1991. Sepsis episodes were treated with 2 doses of urokinase and antibiotics (10 to 42 days) infused through the RAC. One to 2 mL of urokinase (5,000 U/mL) was instilled in the RAC for 1 hour, then removed and repeated 24 hours later. During the study, 224 RACs were placed in 177 children. RACs were in place for a total of 71,134 days (median, 274 days). There were 67 blood culture-positive sepsis episodes occurring in 50 RACs. Fifty-nine sepsis episodes were treated with urokinase and antibiotics and all responded by clearance of organisms from the blood. Three patients (5.1% of urokinase treated) had recurrent sepsis with the same organism within 2 months, were considered treatment failures and had RACs removed. Only 1 of 16 episodes of multiple organism/Candida sepsis led to RAC removal due to inability to cure the infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468646 TI - Laparoscopic Nissen fundoplication in childhood. AB - An obese, 10-year-old boy presented with symptoms of pain and apnea due to gastroesophageal reflux that was unresponsive to medication. A laparoscopic Nissen fundoplication was performed, and the child was discharged from the hospital within 36 hours of the operation. The rationale and technique of a laparoscopic Nissen fundoplication for symptomatic gastroesophageal reflux in childhood is described. PMID- 8468647 TI - The effects of ischemia and reperfusion on intestinal motility. AB - The interdigestive migrating motor complex (MMC) has been demonstrated to be a reliable indicator of intestinal motility and function. The effects of low perfusion on the MMC have never been studied. Fourteen newborn Yorkshire piglets (5 to 18 days old, weighing 2.9 +/- 0.4 kg) underwent celiotomy under general anesthesia with placement of four jejunal electrodes (50 cm apart) as well as a superior mesenteric artery (SMA) Doppler flow probe and a pericardial catheter. Group 1 (n = 5) had operation alone. Group 2 (n = 9) had nonocclusive mesenteric ischemia induced by reversible cardiac tamponade for 5 hours between postoperative days 6 to 12. All subjects had MMC phase III electrical activity, cycling time, and propagation velocity recorded daily. In group 2 MMCs were recorded prior to and during ischemia, and during reperfusion. Group 2 animals had 75% +/- 4% decrease in SMA flow during the tamponade period. During the ischemic period, the MMC cycling time (CT) increased from 67 +/- 10 (mean +/- SEM) to 98 +/- 12 minutes (P < .05) and MMC propagation velocity (PV) decreased to 4.2 +/- 2.2 from a baseline value of 10.5 +/- 1.5 cm/min (P < .05). During reperfusion CT and PV values were not significantly different from baseline. The validity of this model is confirmed by the comparable baseline recordings in groups 1 and 2, and by the return of MMC to baseline values within 4 to 7 hours of reperfusion, as seen in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468648 TI - Elevation of circulating intestinal fatty acid binding protein in a luminal contents-initiated model of NEC. AB - Necrotizing enterocolitis (NEC) continues to produce significant morbidity and mortality, due in part to the difficulty in detecting its initial manifestations at a stage when compromised intestine may potentially be salvaged. We have previously reported our findings that intestinal fatty acid binding protein (I FABP) is a sensitive biochemical marker for early intestinal mucosal injury due to mesenteric ischemia. In this study we evaluated the potential of serum I-FABP as a marker for incipient NEC in a nonischemic model of NEC in the rat. Intraluminal instillation of a solution of casein (10 mg/mL) and calcium gluconate (50 mg/mL) in saline acidified to pH 4.0 with propionic acid resulted in a rapid and prolonged increase in serum I-FABP from a baseline of < or = 4.0 ng/mL to 171 +/- 40 ng/mL. Instillation of the same electrolyte solution with either casein or propionic acid alone resulted in a less dramatic elevation of serum I-FABP to 19 +/- 4 ng/mL and 76 +/- 30 ng/mL, respectively. In both cases baseline values of < or = 4.0 ng/mL were reached within 60 minutes. In control animals, which received saline alone, serum I-FABP was undetectable throughout the experiment. Simultaneously, we found that serum hexosaminidase, a putative biochemical marker for intestinal ischemia and NEC, was unchanged in all groups. Light microscopy of the intestinal specimens obtained three hours after instillation of casein and organic acid demonstrated superficial villus necrosis and villus blunting, but no areas of transmural necrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468649 TI - Thoracic neuroblastoma: a Pediatric Oncology Group study. AB - Ninety-six patients with thoracic neuroblastoma were studied in a prospective fashion. Median age at presentation was 0.9 years. Forty-eight percent of the patients presented with stage A disease, 20% stage B, 13% stage C, 17% stage D, and 2% stage DS. Seventy-five patients have been followed for greater than 4 years. A posterior mediastinal mass was diagnosed on incidental chest roentgenograms performed for nontumor-related symptoms in 49% of the cases. Sixteen percent of the cases presented with neurological symptoms and 14% of the patients presented with acute respiratory distress. Urinary catecholamines were elevated in 76% of the cases. Complete surgical resection was carried out in 47% of the cases, while incomplete resection or biopsy was performed in 45%. No operation was performed in 3 patients. Minor surgical complications occurred in 20% of the patients, and 3% of the patients had significant perioperative complications. One patient died as a complication of therapy. Overall actuarial survival was 88% at 4 years. This study confirms the favorable outcome in children with mediastinal neuroblastoma. The basic biology of thoracic neuroblastomas seems to differ from that of other sites in that the majority of patients present at a younger age with localized disease or regional lymph node metastases, and have an improved survival even after correcting for age and stage. While complete excision is recommended, if possible, radical surgical procedures are not indicated since an excellent prognosis is associated with combined modality therapy. PMID- 8468650 TI - Rectal mucosectomy: a definitive approach to extensive hemangiomas of the rectum. AB - Major rectal bleeding may occur in children and adults who have extensive hemangiomatous involvement of the pelvis and rectosigmoid colon, as in the Kleppel-Trenaunay syndrome (KTS). Conventional surgical techniques such as bowel resection and colostomy have often been associated with large blood loss and/or incontinence. We have used a new approach to this problem utilizing rectal mucosectomy to eliminate the bleeding rectal mucosa and to preserve anal function. Four patients born with KTS eventually developed major rectal bleeding and were successfully corrected by this surgical approach. Two were females and two males. Ages ranged from 4 to 25 years at the time of surgery. The patients developed rectal bleeding leading to chronic anemia during the first decade of life. Rectal bleeding gradually increased requiring multiple transfusions (2 to 20 units) prior to surgery. Patient 1 underwent resection of the rectosigmoid colon, with rectal mucosectomy and endorectal coloanal anastomosis. The Nd:YAG laser was used on 3 occasions on the distal remaining rectal mucosa. Patients 2, 3, and 4 underwent sigmoid resection, transanal rectal mucosectomy, and a coloanal anastomosis, with minor YAG laser therapy in one patient. Blood loss during surgery was minimal. Follow-up ranged from 1.5 to 4 years. All have excellent sphincter control with no incontinence. No strictures or sepsis occurred following surgery. Rectal bleeding was eliminated in all 4 patients. This sphincter-saving approach should be considered in patients with extensive hemangiomas of the rectosigmoid colon because of its remarkable effectiveness and safety. PMID- 8468651 TI - Improved survival in biliary atresia patients in the present era of liver transplantation. AB - Therapy for patients with biliary atresia (BA) has become controversial, with orthotopic liver transplantation (OLTx) suggested in place of portoenterostomy. This is based on the unpredictable success of portoenterostomy, and the increased difficulty of the OLTx procedure following prior extensive liver surgery. The survival rate reported here for infants transplanted after unsuccessful portoenterostomy does not support this approach. OLTx was undertaken in 37 patients when end-stage liver failure followed primary portoenterostomy. Recipient age ranged from 6 months to 14 years (median, 13 months), and weight ranged from 5 to 45 kg (median, 8 kg) at the time of OLTx. Reduced-size allografts were used as the primary allograft in 25 patients (23 left lobe), and 12 received whole-organ allografts. Retransplantation was required in 5 patients, each received a reduced-size allograft. There was no increased incidence of vascular complications, primary nonfunction, irreversible rejection, intestinal perforation, biliary complications, sepsis, or lymphoma comparing the BA patients with all other non-BA patients who had undergone OLTx (all P = .16). There was no statistically significant difference in mean operative blood loss between BA patients (EBL = 1.99 BV) and non-BA patients (1.50 BV) (P = .14). Actuarial survival for the series of BA patients was 89% at 1 year, and 80% at 2 years. Following the introduction of reduced-size allografts, donor organs were selected for use with a priority on donor stability. The actuarial survival for BA patients during this time has improved to 96% at 1 year, and 91% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468652 TI - The influence of portoenterostomy with stoma on morbidity in pediatric patients with biliary atresia undergoing orthotopic liver transplantation. AB - A portoenterostomy (PE) procedure for extrahepatic biliary atresia (EHBA) is sometimes performed with a stoma in an attempt to reduce the incidence of acute cholangitis. The purpose of this study was to determine if the presence of a stoma increased the complication rate of patients undergoing orthotopic liver transplantation (OLT) for EHBA. The medical records of 42 consecutive patients with EHBA who underwent primary OLT between October 1988 and October 1991 were retrospectively reviewed. Three patients were excluded, since their grafts were lost within 3 days of OLT. The remaining 39 patients were divided into three groups: no PE (n = 7), PE without stoma (n = 23), and PE with stoma (n = 9). The mean age of the whole group was 19.62 +/- 24.37 months, with a range of 5 to 132 months. Mean weight was 9.62 kg, with a range of 4.2 to 41 kg. Survival at 3 and 12 months as well as number of retransplantations were similar among the three groups. However, at the time of OLT increased morbidity was observed, consisting of increased operative time and number of reoperations, whether or not the stoma had been closed prior to OLT. PMID- 8468653 TI - Hepatobiliary dysfunction during total parenteral nutrition is caused by infusate, not the route of administration. AB - Cholestatic jaundice is the major complication of total parenteral nutrition (TPN). Both the intravenous (IV) route of nutrition and the enteral fast have been implicated as causes of TPN-associated cholestasis (TPN-AC). The purpose of this study was to determine whether TPN-AC is caused by the TPN solution itself or the IV route of administration and enteral fast. Prepubescent rabbits (n = 24) were divided into four groups: CONTROL, fed standard lab chow; TPN, received a standard hyperalimentation solution of dextrose, Aminosyn, and lipids via the jugular vein; ENT, received the same hyperalimentation solution via a duodenostomy tube; and OSM, received a polymeric formula (Osmolite) via a duodenostomy tube. After 14 days on these diets, we measured bile flow, bile acid excretion, sulfobromophthalein (BSP) excretion, plasma amino acid profile, serum liver enzymes, and liver histology. Statistical analysis was by analysis of variance. Hyperalimentation solution significantly depressed hepatobiliary function, whether it was given IV or by gut. Bile flow in both the TPN (36.4 microL/kg/min) and ENT (46.2) groups was significantly less than CONTROL (84.5) or OSM (62.9). Hepatic secretory function, measured by excretion of the cholephilic dye BSP, was depressed in both TPN and ENT (57% and 55% of IV dose excreted in bile over 60 minutes, respectively) compared with CONTROL (84%) or OSM (71%). Serum liver enzymes were normal in all groups. Histological injury similar to TPN-AC in humans (portal inflammation and hepatocyte degeneration) was seen in both groups receiving the hyperalimentation solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468654 TI - Side-to-side lienorenal shunt without splenectomy in noncirrhotic portal hypertension in children. AB - Noncirrhotic portal hypertension is a common cause of upper gastrointestinal bleeding in infants, children, and adolescents in India. More than one major bleeding episode, severe hypersplenism, presence of fundal varices, rare blood group, remoteness from the hospital, and patient noncompliance to sclerotherapy formed the main indications for shunt surgery. One hundred four cases of noncirrhotic portal hypertension (age range, 18 months to 20 years) underwent side-to-side lienorenal shunt (SSLR) without splenectomy in a period of 15 years. Splenic veins varying in diameter from 4 to 18 mm and in length from 3 to 4 cm were skeletonized through the root of transverse mesocolon and a shunt of at least 1.5 cm in diameter was constructed. At a mean follow-up of 54 months, 87% of shunts were patent, 13% of shunts were blocked, and 2% were inadequate. Ten percent of the children had rebled, all of whom had a blocked shunt. Growth and development was normal and no patients developed encephalopathy. There was a good correlation between shunt patency on splenoportography and endoscopic disappearance of varices, reduction in the size of spleen and splenic pulp pressure, and improvement of hypersplenism. PMID- 8468655 TI - Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings. AB - The perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis (MPS) are presented. They underwent a detailed preoperative assessment and were anesthetized 141 times. An intravenous induction technique was used in most patients. It was easier to see the vocal cords, during laryngoscopy, in children with Hurler syndrome (HS) when they were younger (23 v 41 months, P < or = .01) and smaller (12 v 15 kg, P < or = .05). Preoperative obstructive breathing was associated with a significantly higher incidence of postextubation obstruction (P < or = .05). A total of 28 children underwent bone marrow transplantation (BMT); this reversed upper airway obstruction and also reversed intracranial hypertension. In children with HS, the incidence of odontoid dysplasia was 94%; 38% demonstrated anterior C1-C2 subluxation. Head and neck manipulation was limited in children with cervical spine defects. None of the 30 patients experienced spinal cord morbidity. One child suffered an intraoperative stroke; another, pulmonary edema. Severe and extensive coronary obstruction was responsible for 2 intraoperative deaths. Coronary angiography underestimated coronary artery disease. PMID- 8468656 TI - Early use of cisplatin is safe after partial hepatectomy. AB - Although cisplatin is widely used in the treatment of liver tumors, little information is available concerning its effect on liver regeneration. This report evaluates the effect of cisplatin on liver regeneration after hepatectomy (HPx). One hundred sixty male Sprague-Dawley rats were placed into five experimental groups following 70% hepatectomy. Group I (untreated controls, n = 32) received 0.9% saline intraperitoneally (IP); group II (n = 31), cisplatin 4 mg/kg IP; group III (n = 36), cisplatin 10 mg/kg IP; group IV (n = 34), cisplatin 20 mg/kg IP; and group V (n = 27), doxorubicin 6 mg/kg intravenously (IV). Five additional sham groups underwent celiotomy without hepatectomy (n = 106) followed by the above treatment protocols. Liver regeneration was evaluated by liver weight, DNA incorporation measured by tritiated thymidine (3H-TdR), and quantitative image analysis (QIA) of hepatic nuclei at 18, 24, 36, 48, and 72 hours, and 5 days postoperatively. 3H-TdR incorporation peaked at 36 hours and was similar in hepatectomized controls group I (404 +/- 110 counts per minute [CPM]/mg liver weight) and cisplatin-treated rats (groups II to IV) (P > .05, ANOVA). All sham groups were similar to controls. QIA of feulgen-stained touch preps identified polyploid, stem line, and proliferating nuclei in both controls and treated groups. At 36 hours, QIA showed differences in mitotic status of sham, control, and adriamycin-treated HPx rats, consistent with 3H-TdR incorporation. In contrast, although cisplatin-treated rats receiving 4 mg/kg showed proliferating nuclei, QIA demonstrated decreasing hepatocyte proliferation with higher doses of cisplatin (10 mg/kg, and 20 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468657 TI - Combined preoperative and postoperative immunotherapy for murine C1300 neuroblastoma. AB - Preoperative treatment of murine C1300-neuroblastoma (C1300) with triple immunotherapy using low-dose cyclophosphamide (CY), retinyl palmitate (RP), and interleukin-2 (IL2), followed by tumor resection leads to significant initial tumor control and prolonged survival. However, because long-term tumor recurrence is 67%, the efficacy of continued postoperative immunotherapy is now evaluated. Thirty-two A/J mice with 1 cm subcutaneous C1300 tumors were treated for 13 days with CY-100 mg/kg, intraperitoneally (IP), on day 2 of treatment then 25 mg/kg on day 9, RP-2500 IU IP 2 x/week, and IL2 1.6 x 10(5) U IP BID on days 4 to 9 and 11 to 13. On day 14, mice were divided into five treatment groups: (1) OP (operated tumor resection, n = 6); (2) OP+CY (resection and postoperative CY, n = 7); (3) OP+CY+RP (resection and postoperative CY+RP, n = 7); (4) OP+CY+RP+IL2 (resection and postoperative CY+RP+IL2, n = 7); and (5) CY+RP+IL2 (continued CY+RP+IL2 with no resection, n = 5). Survival and postoperative tumor recurrence were followed for 60 days. The cure rates were group 1 33% (2/6), group 2 43% (3/7), group 3 29% (2/7), group 4 71% (5/7), and group 5 20% (1/5). After surgery, tumors that recurred did so in 8 to 22 days, with no statistical difference noted between groups. MHC class I antigenic expression of tumors resected on day 14 and recurrent tumors was determined with monoclonal antibodies and flow cytometry. In tumors resected on day 14, class I expression measured by mean fluorescence, was 374.8 +/- 27.40.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468658 TI - Biology of fetal repair: the presence of bacteria in fetal wounds induces an adult-like healing response. AB - The minimal acute inflammatory response to tissue injury is one of the most dramatic differences between fetal and adult wound healing. Considering the prominent role of inflammation in adult tissue repair, this study tested the hypothesis that the minimal fetal inflammatory response to tissue injury plays a central role in the "scarless" fetal repair process. Sponge implants were treated with lethally irradiated or live bacteria and placed subcutaneously in fetal rabbits to test the ability of the fetus to mount an acute inflammatory response to bacterial antigens present at the wound site and to analyze the effects of this inflammatory response on fetal fibroplasia and neovascularization. After harvest, these implants were examined histologically for inflammation, fibroblast infiltration, collagen deposition, and neovascularization, and collagen deposition was measured using hydroxyproline quantitation by high-performance liquid chromatography. Bacteria-treated implants showed dose-dependent acute inflammatory responses and significant increases in collagen deposition compared with control sponges. Implants containing live bacteria demonstrated maximal fibroplasia and neovascularization. These findings suggest that, despite neutropenia and immaturity of the fetal immune system, the fetus is capable of mounting an acute inflammatory response to avirulent bacteria present at the wound site. Fetal inflammatory cells which respond to this bacterial stimulus appear capable of initiating an adult-like healing response. Thus, by failing to provide a bacterial stimulus for leukocyte recruitment at the site of tissue injury, the sterile fetal environment appears to play a role in effecting "scarless" fetal wound healing. PMID- 8468659 TI - Transverse mucosal preputial flap for repair of severe hypospadias and isolated chordee without hypospadias: a 350-case experience. AB - Three hundred patients with hypospadias and 50 patients with isolated chordee without hypospadias were operated on and followed by the same surgeon. A very low postoperative urethrocutaneous fistula rate (4.8%) was related to complete cutaneous coverage of the neourethra. The incidence of stenosis, noted in 8% of the cases, has progressively decreased with improvement of technical details and with growing experience. A total of 75% of the patients were corrected with a single operative procedure. Good disponibility of penile skin rendered a second intervention always easy. PMID- 8468660 TI - Mullerian inhibiting substance in the diagnosis and management of intersex and gonadal abnormalities. AB - Mullerian inhibiting substance (MIS), a gonadal hormone important in sexual differentiation, is high (10 to 70 ng/mL) in human male serum postnatally for several years before declining during the peripubertal period, but is undetectable in female serum until the onset of puberty. The sexually dimorphic secretion of MIS suggested possibilities for its use in several clinical settings. Thirty-one patients with intersex and gonadal anomalies from 17 institutions were therefore evaluated between 1989 and 1992 with an MIS enzyme linked immunosorbent assay (ELISA). Serum MIS levels correlated with the presence of testicular tissue in two patients with suspected anorchia, five patients with male pseudohermaphroditism, and eight other intersex patients with undescended testes, dysgenetic gonads, or ovotestes. In these latter patients, serial MIS values were also helpful to confirm complete removal of gonadal tissue postoperatively. MIS may be a more sensitive marker for the presence of testicular tissue than serum testosterone levels, both before and after the neonatal androgen surge, and, consequently, may obviate the need for human chorionic gonadotropin stimulation in the evaluation of certain intersex disorders. In values were useful in differentiating the underlying etiology of the disorder. Four patients with undetectable levels have presumptive MIS gene mutations, while 7 others with MIS values of 2 to 45 ng/mL may have bioinactive hormone of MIS receptor defects. Finally, two young girls with ovarian granulosa cell tumors had elevated MIS values that fell from 18 to 2 ng/mL and from 6.5 to 1 ng/mL during postoperative follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468661 TI - Congenital bronchobiliary fistula: management of the involved hepatic segment. AB - We present three children with congenital bronchobiliary fistula (CBBF). The first infant underwent resection of the fistula at age 3 weeks and was reported as a success. She returned 7 years later with bilious expectoration for which a second thoracotomy was performed. One year thereafter a bile collection in the right chest required open drainage. Subsequently, the left hepatic lobe was resected. The second child was initially diagnosed as suffering from gastroesophageal reflux. He underwent a fundoplication and a gastrostomy at age 9 months. Persistence of bilious sputum led to the diagnosis of CBBF at age 23 months. The fistula was excised through a right thoracotomy. The distal end was injected demonstrating an arborization involving the entire left hepatic lobe. Since there was no communication with the remaining biliary tree or the intestine, a left hepatectomy was performed. The third child was reported in a communication focusing on the diagnosis of CBBF by hepatobiliary scintigraphy. Her history is almost identical to the second patient. However, instead of a hepatectomy, she underwent a Roux-en-Y drainage of the fistula. The three children had uneventful recoveries and are well. We believe that an abnormal biliary tract should be studied by contrast injection. If no decompressing communication with the normal biliary ducts or the duodenum can be demonstrated, the involved hepatic segment should be resected or internally drained. Children who underwent simple fistula excision must have close long-term follow-up. PMID- 8468662 TI - The natural history of congenital diaphragmatic hernia and pulmonary hypoplasia in the embryo. AB - Up to now, descriptions of the natural history of congenital diaphragmatic hernia (CDH) associated with pulmonary hypoplasia (PH) are based exclusively on observations made in the fetal period. However, nothing is known about the events that take place in an embryo with CDH. Recently, an animal model of CDH and PH has been established in rat embryos to study the embryology and natural history of this lesion. We exposed 36 pregnant Sprague-Dawley rats to a single dose of 100 mg nitrofen on day 11 of pregnancy. A total of 356 staged embryos and fetuses from day 13 to day 21 were studied by light and scanning electronmicroscopy. The litters of 9 untreated rats (124 normal age-matched embryos and fetuses) served as controls. The abnormal development of the diaphragmatic anlage was first seen in embryos aged 13 to 14 days. A defect appeared in the dorsal part of the diaphragm, normally on the right side. The liver grew through this defect early on. Gut was found in an intrathoracic position only in the very late stages (day 21/22) and newborns. Compared to controls, lungs of nitrofen-embryos with CDH were smaller, depending on the size of liver found in the thoracic cavity. Histologically, compression of lung was absent at these stages. Most authors speculate that CDH results because the pleuroperitoneal canals fail to close at the end of the embryonic period (ie, week 8 to 10 in human development) leading to a defect in the dorsolateral region of the diaphragm. However, contradictory to this assumption, our findings indicate that diaphragmatic defects develop in early embryonic life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468663 TI - Pathophysiology of congenital diaphragmatic hernia. IV: Renal hyperplasia is associated with pulmonary hypoplasia. AB - The hypothesis of this article is that growth of the fetal lung is stimulated by a pulmonary growth factor (PGF) produced by the kidneys, which is modulated by a feedback signal from the lungs, a pulmonary-derived renotropin (PDR). In the fetus with pulmonary hypoplasia (PH), the lungs may maximally stimulate this feedback loop to release more PDR, resulting in continual stimulation of the kidneys and renal enlargement. If such a schema plays a role in the pathophysiology of PH, newborn infants with congenital diaphragmatic hernia (CDH) or chronic amniotic fluid leak (CAFL) should have enlarged kidneys. To investigate this hypothesis, we created models of CDH in fetal lambs and CAFL in fetal rabbits, and then analyzed lung (Lu) and kidney (K) growth. When compared to controls, newborn CDH lambs had significantly smaller lungs and larger kidneys. The lungs were hypoplastic as defined by either decreased lung weight/body weight (LuW/BW), lung DNA/body weight (Lu DNA/BW), or lung total protein/body weight (LuTP/BW) (P < .01). Renal hyperplasia was confirmed by KW/BW, K DNA/BW (P < .01), and KTP/BW (P < .05). An inverse relationship between lung size and kidney size could be described by the equation KW/BW = 1.04 - 0.12 LuW/BW (r = -.75). The CAFL model in newborn rabbits produced severe oligohydramnios when compared with controls (P < .01). This resulted in fetuses with smaller lungs and larger kidneys as compared with those of controls. The lungs were significantly smaller and more hypoplastic than controls when compared by LuW (P < .01), LuW/BW (P < .01), Lu DNA/BW (P < .05), and Lu TP/BW (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468664 TI - Biochemical immaturity of lungs in congenital diaphragmatic hernia. AB - Neonates with congenital diaphragmatic hernia (CDH) continue to have unacceptably high mortality rates. To better understand the associated pulmonary pathology we measured biochemical parameters of lung maturity in neonatal rats with or without congenital diaphragmatic hernia created by maternal feeding of a single dose of nitrofen on day 9.5 or day 11.5 of gestation. Lungs from neonatal rats with large CDH (n = 9, 5 right-sided, 4 left-sided) had a significantly lower lung weight (P = .0001), lung weight/body weight ratio (P = .0001), disaturated phosphatidylcholine (DSPC) per microgram DNA (P < .005), total DSPC (P = .0001), total DNA (P < .05), protein per microgram DNA (P < .05), and total protein content (P < .005) when compared with lungs from the litter mates without congenital diaphragmatic hernia (n = 10). The lungs of rats with hernia also had significantly higher DNA concentrations (P < .05) and glycogen concentrations (P < .05). These data demonstrate that lungs in neonatal rats with large CDH are biochemically immature. Treatment directed toward correcting the pulmonary biochemical immaturity of affected fetuses before birth may improve the prognosis for these babies. PMID- 8468665 TI - Altered diaphragm function modifies neonatal lung growth: biologic morphometric assessment. AB - Thoracic volume relationships supported by the diaphragm are important mechanical components of neonatal lung growth. Alterations modify regional lung growth. We used stereologic morphometry to study effects of altered diaphragm function on alveolar growth in neonatal pigs. Nine piglets (1 mo) were divided into three groups: unilateral phrenectomy, noncompliant patch replacement of diaphragm, and sham. Seven days later lungs were fixed in situ with 2.5% glutaraldehyde by airway installation at 20 cm H2O. Five 1-mm cubes were cut from lung corresponding to apex/RUQ(A), base/RLQ(B), apex/LUQ(C), and base/LLQ(D) and prepared for light microscopy (n = 25/quad/animal). Stereologic morphometry involved point counting for air volume density and point intersect to determine the surface area density of the alveolar spaces. Results were analyzed for variance and by Tukey range testing. Variance of air volume % between groups quadrants B, C, D had decreased air volume % in phrenectomy group compared with patch and sham group (P < .05). Variance of air volume % within groups, for phrenectomy group A (81.5%), is different from all others (B = 70.6%, C = 75.5%, D = 66.7%); C is different from D (P < .05). For patch and sham group, D (P = 74.8%, S = 80.7%) is different from A (P = 84.1%, S = 86.6%) and C (P = 86.2%, S = 84.4%). Variance of surface area density between groups--quadrant D had increased surface area density % in phrenectomy group compared to sham group (P < .05). Variance of surface area density % within groups, for phrenectomy group, A (37.9 mm-1) is different from D (55.7 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468666 TI - Intratracheal pulmonary ventilation and congenital diaphragmatic hernia: a report of two cases. AB - Previous studies from our institution have shown that neonates with congenital diaphragmatic hernia (CDH), whose best postductal PaO2 (BPDPO2) was less than 100 mm Hg while on maximal conventional mechanical ventilation (CMV), had a mortality exceeding 90%. When combined with extracorporeal membrane oxygenation (ECMO), the mortality rose to 100% in those infants who developed hypercarbia following decannulation. Historically, those patients have required increasing ventilator support, leading to iatrogenic lung damage, and eventual death. Intratracheal pulmonary ventilation (ITPV) using the reverse thrust catheter (RTC) developed by Kolobow incorporates a continuous flow of humidified gas through a reverse Venturi catheter positioned at the distal end of the endotracheal tube. In animal studies, ITPV was shown to result in a reduced physiological dead-space (VD), to facilitate expiration, and to enhance CO2 elimination. In our current study, we have applied ITPV in two neonates with CDH who could not be weaned from ECMO because of uncontrollable hypercapnia, and who met above criteria for 100% mortality. In both cases, ITPV restored normal PaCO2 at low peak inspiratory pressure (PIP) with a substantial decrease in VD. We believe ITPV is suited to ventilating newborns with CDH in whom barotrauma is known to be common. Beyond its present use, ITPV may be useful to ventilate children with other forms of respiratory failure, and should be so considered along with other now available methods of mechanical pulmonary ventilation. PMID- 8468667 TI - Lung injury produced by moderate lung overinflation in rats. AB - In models using both intact animals and isolated lungs of rats, rabbits, lambs, and dogs, application of high airway pressure and resultant lung overdistension has been shown to cause lung injury. Under pathological conditions, the more normal portions of the lung may be subjected to relative overdistension when supranormal airway pressures are used. A small animal model of lung overdistension is presented here to demonstrate that lung injury can be caused by moderate lung overdistension. Rats were anesthetized with Ketamine and pentobarbital. A tracheostomy was performed and arterial and central venous catheters placed. The animal was placed in a plethysmograph and an infant ventilator was used to provide mechanical ventilation. In the first experiment, animals in group A (n = 6, control) were ventilated at tidal volume (TV) of 5 mL/kg for 5 hours. Animals in group B (n = 6) were ventilated at TV 15 mL/kg for 60 minutes and then were returned TV of 5 mL/kg for the remainder of the experiment. Animals in group C (n = 5) were ventilated at TV 20 mL/kg for 60 minutes and then returned to TV 5 mL/kg. Static lung compliance and arterial blood gasses were measured. Wet and dry lung weight were obtained after sacrifice. In the second experiment, animals in group D (n = 4, control) were ventilated at TV 5 mL/kg for 240 minutes and killed. Animals in group E (n = 4) were ventilated at TV 20 mL/kg for 60 minutes, returned to TV 5 mL/kg, and killed at 240 minutes. Fluorescein-labeled albumin was administered to each animal prior to mechanical ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468668 TI - A test of the social support deterioration model in the context of natural disaster. AB - This prospective longitudinal study examined stress-mediating potentials of 3 types of social support: social embeddedness, perceived support from nonkin, and perceived support from kin. As participants in a statewide panel study, 222 older adults were interviewed once before and twice after a severe flood. It was hypothesized that disaster exposure (stress) would influence depression directly and indirectly, through deterioration of social support. LISREL analyses indicated that postdisaster declines in social embeddedness and nonkin support mediated the immediate and delayed impact of disaster stress. No evidence was found for the mediational role of kin support. Findings are in accord with conceptualizations of social support as an entity reflecting dynamic transactions among individuals, their social networks, and environmental pressures. PMID- 8468669 TI - Perceiver self-presentational goals as moderators of expectancy influences: ingratiation and the disconfirmation of negative expectancies. AB - Self-fulfilling prophecy processes enable people to confirm their negative expectancies for others. The perceiver goal of ingratiation was hypothesized to alter this behavioral dynamic and thus lead perceivers to disconfirm their negative expectancies. In an interview setting, we manipulated interviewer Ss' expectancies and interaction goals. As anticipated, "no goal" interviewers were relatively cold and challenging toward their negative-expectancy applicants; as a result, these applicants performed somewhat less favorably, consistent with interviewer expectancies. In contrast, "liking goal" interviewers were relatively warm and unthreatening toward their negative-expectancy applicants; as a result, these applicants performed favorably, disconfirming interviewer expectancies. These data support a framework in which perceiver self-presentation goals are conceptualized to moderate the expectancy-confirmation process. PMID- 8468670 TI - Self-esteem, mood, and self-evaluation: changes in mood and the way you see you. AB - Three studies found that self-esteem moderates the relation between mood and self evaluation. In Study 1, a standard mood-induction procedure was used to induce positive, negative, or neutral moods in low self-esteem (LSE) Ss and high self esteem Ss. Afterward, Ss evaluated their specific qualities and characteristics (e.g., How smart are you? How kind are you?). Both self-esteem groups evaluated themselves favorably in a positive mood, but LSE Ss were more apt to lower their self-evaluations in a negative mood. Study 2 found a similar, though weaker pattern using a noncognitive, musical mood induction; Study 3 found that these effects occur with variations in naturally occurring mood over a 6-week period. The authors suggest that the tendency for LSE people to respond to negative moods with self-depreciation contributes to psychological distress. PMID- 8468671 TI - Marital satisfaction, depression, and attributions: a longitudinal analysis. AB - This study examined the longitudinal relation between causal attributions and marital satisfaction and tested rival hypotheses that might account for any longitudinal association found between these variables. Data on attributions for negative partner behaviors, marital satisfaction, depression, and self-esteem were provided by 130 couples at 2 points separated by 12 months. To the extent that spouses made nonbenign attributions for negative partner behavior, their marital satisfaction was lower a year later. This finding was not due to depression, self-esteem, or initial level of marital satisfaction, and also emerged when persons reporting chronic individual or marital disorder were removed. Results support a possible causal relation between attributions and marital satisfaction. PMID- 8468672 TI - Stability of babyfaceness and attractiveness across the life span. AB - Differential, structural, and absolute stability of babyfaceness and attractiveness at 5 ages were investigated. Attractiveness had differential stability across the life span. Babyfaceness had differential stability from childhood through the 30s for males and through adolescence for females. Consistent with sexual dimorphisms in facial maturation, males had less differential stability in babyfaceness from childhood to puberty than females. Structural stability of facial appearance, as reflected in the relationship between babyfaceness and attractiveness across the life span, was low, with these qualities positively related for females in childhood and for both sexes in their 30s and 50s but unrelated in puberty and adolescence. Absolute stability of babyfaceness and attractiveness was also low, with mean levels decreasing across the life span. Contrary to cultural stereotypes, age-related decreases in attractiveness were equal for male and female Ss. PMID- 8468673 TI - Behavioral manifestations of personality: an ecological approach to judgmental accuracy. AB - The present study concerns connections between personality traits, the behaviors by which they are manifest, and the behaviors by which they are judged. One hundred forty undergraduate Ss were videotaped in 2 social interactions, and 62 behaviors were coded from each tape. Separately, personality descriptions were obtained from knowledgeable informants. A pair of "strangers" viewed each videotape then also provided personality descriptions. Other Ss rated the diagnosticity of the 62 behaviors for each of the Big Five personality traits. The diagnosticity ratings predicted how behavioral cues would be used by strangers and were closely related to their actual relevance as indexed by their correlations with informants' judgments. These findings speak to the general accuracy of personality judgments, the development of methods to improve accuracy, and the value of reintegrating traditionally separate concerns of personality and social psychology. PMID- 8468674 TI - Changes in and stability of hostile characteristics: results from a 4-year longitudinal study of children. AB - Changes in and stability of hostility characteristics and their relationship to age, sex, and family support were examined among 108 10-18-year-olds in a 4-year longitudinal study. Clinical ratings of Structured Interview potential for hostility, self-reported Minnesota Multiphasic Personality Inventory-derived hostile attitudes, and perceptions of family support were obtained at study entry and at follow-up when subjects were ages 15-21. Results showed relative stability of hostility rankings across 4 years, with males being more hostile than females. Both sexes increased in hostility over time, with the greatest increase in Ss who perceived low family support at follow-up and whose parents perceived high family support at study entry. Results are consistent with notions that early signs of hostility are risk factors for later development of coronary disease and that family environment influences development of hostility. PMID- 8468675 TI - Prediction of drug distribution in distribution dialysis and in vivo from binding to tissues and blood. AB - Relationships between the binding and the distribution of drugs have been studied in vitro and compared with in vivo data. By use of a standardized technique of distribution dialysis, 10 model drugs were allowed to be distributed among blood and homogenates of seven tissues. The drugs represented a variety of distinct molecules with different lipophilicities, ionization constants, and binding characteristics. The tissue/blood drug concentration ratios were below unity for salicylic acid and phenylbutazone, at about unity for antipyrine (phenazone) and morphine, and above unity for two barbiturates and four basic lipophilic drugs. The binding of the 10 drugs to blood and homogenates of seven tissues was determined by use of conventional equilibrium dialysis and experimental conditions identical to those used in distribution dialysis. From these binding values (free fractions), the theoretical concentration ratios were calculated. There was a good correlation between the calculated values and those determined by distribution dialysis. Thus, the distribution of drugs in the in vitro model of distribution dialysis clearly is the result of binding competition and is predictable from binding values. The correlation between distribution in vitro (or calculated from binding values) and distribution in vivo, on the basis of literature data, indicated a reasonable agreement for antipyrine and the acidic lipophilic drugs used, as well as for the basic lipophilic drugs, with respect to the brain, muscle, and adipose tissue. However, the distribution of the latter drugs in the lungs, liver, and kidneys was grossly underestimated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468676 TI - Automated drug dissolution monitor that uses a UV-visible diode array spectrophotometer. AB - A method for performing multicomponent analysis in drug dissolution testing without chromatographic separation is presented. Aliquots from dissolution vessels are automatically transferred to a UV-visible diode array spectrophotometer, spectra are measured, and the aliquots are returned to the testing vessels. A full-spectrum calibration method based on principal-component regression is used to simultaneously determine the concentrations of active ingredients and to account for interferences due to excipients in a tablet formulation. The system was evaluated with two commercial pharmaceutical formularies; the first contained pseudoephedrine hydrochloride and chlorpheniramine maleate, whereas the second was a mixture of phenylpropanolamine hydrochloride and chlorpheniramine maleate. The selections of standard mixtures for calibration and validation were based on a factorial design. PMID- 8468677 TI - Quantitative structure-activity relationships for substituted aminotetralin analogues. I: Inhibition of norepinephrine uptake. AB - Quantitative structure-activity relationships of 57 substituted aminotetralin analogues, an overview of their syntheses, and their pharmacological activity are described in this study. Lipophilic substituents at R3 as well as the overall lipophilicity of the molecule contribute toward increasing the inhibitory potency. An ethyl group is preferred, and a group larger than a propyl is not desirable as a nitrogen substituent. Among the ring substituents examined, an hydroxy group at the R6 position and either an unsubstituted R9 position or a methoxy substituent at the R9 position increase the inhibitory potency, whereas a methoxy group at the R7 position decreases inhibitory potency. PMID- 8468678 TI - Hydrolysis of saturated soybean phosphatidylcholine in aqueous liposome dispersions. AB - Hydrolysis kinetics of saturated soybean phosphatidylcholine (PC) were investigated as a function of pH, temperature, buffer concentration, buffer species, and ionic strength in aqueous liposome dispersions. A high-performance liquid chromatography method was used to separate PC and the hydrolysis products. Hydrolysis of PC followed pseudo first-order kinetics. Hydrolysis of fatty acid esters at sn-1 and sn-2 positions initially resulted in the formation of 2-acyl lyso-phosphatidylcholine and 1-acyl lyso-phosphatidylcholine; because of acyl migration, the most stable isomer of lyso-phosphatidylcholine, 1-acyl lyso phosphatidylcholine, was formed predominantly. General acid-base catalysis was observed for acetate and Tris ions. The pH profiles at 40 and 70 degrees C for a buffer concentration of 0.05 M showed a minimum hydrolysis rate at about pH 6.5. The relationship between the observed rate constant and temperature could be described adequately by the Arrhenius equation below and above the phase transition temperature of saturated soybean PC (52 degrees C). PMID- 8468679 TI - High-performance liquid chromatographic method for assay of otilonium bromide, diazepam, and related compounds in finished pharmaceutical forms. AB - A rapid, simple, stability-indicating assay procedure for otilonium bromide, a smooth muscle relaxant agent, and diazepam in composite tablet analysis was developed with high-performance liquid chromatography. The tablet matrix was dissolved with water, and drugs were extracted with acetonitrile containing an internal standard. An aliquot was centrifuged and chromatographed on a 5-microns, reversed-phase column with 0.5 M sodium acetate trihydrate buffer containing 5 mM 1-heptanesulfonic acid monohydrate sodium salt:methanol (30:70; v/v; adjusted to pH 6.0 with glacial acetic acid) as the mobile phase. The selectivity of the chromatographic system was demonstrated by resolving both compounds from various potential degradation products of each compound. The method is linear, quantitative, and reproducible. PMID- 8468680 TI - Photodegradation of benzydamine: phototoxicity of an isolated photoproduct on erythrocytes. AB - Benzydamine hydrochloride (Tantum, 1) is a photoallergic and phototoxic anti inflammatory and analgesic agent. This drug is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of benzydamine under oxygen or argon at 300 nm affords 5-hydroxybenzydamine (2) and 2-beta dimethylaminopropyl-1-benzylindalolin-3-one (3) as the main isolated and spectroscopically identified photoproducts. A radical intermediate was evidenced by thiobarbituric acid that was used as a radical sonde, as well as by the dimerization of cysteine. Erythrocyte lysis photosensitized by 1, 2, and 3 was investigated. PMID- 8468681 TI - Transmucosal delivery of methionine enkephalin. I: Solution stability and kinetics of degradation in various rabbit mucosa extracts. AB - To evaluate the feasibility of transmucosal delivery of methionine enkephalin (Tyr-Gly-Gly-Phe-Met; Met-Enk), it is important to first investigate its physicochemical and enzymatic stability. The kinetics of degradation of Met-Enk in aqueous solution was determined at pH 2.01-9.84 and 37-45 degrees C by high performance liquid chromatography. The first-order rate constant (k) was calculated, and the log k-pH profile showed that Met-Enk is most stable at pH approximately 5.0. Various mucosae excised from rabbit were mounted on Valia Chien permeation cells and exposed to isotonic phosphate buffer at physiologic pHs. Mucosal and serosal extracts were collected from the donor and receptor solutions, respectively. The degradation of Met-Enk in the extracts followed first-order kinetics, but no significant difference in the degradation rates was observed between mucosal and serosal extracts, regardless of the type of mucosa used. Degradation was most rapid in the extracts of rectal mucosa, followed by vaginal and nasal mucosae. The major metabolites were Des-Tyr-Met-Enk and Tyrosine (Tyr), indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested that dipeptidyl peptidase and dipeptidyl carboxypeptidase could play some roles in the degradation of Met-Enk. The degradation pathways of Met-Enk were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Met-Enk in the mucosal extracts. PMID- 8468682 TI - In vitro release of testosterone from suppository bases and in vivo absorption studies in human males. AB - Diffusion rates of testosterone from various suppository bases with and without surfactants were determined. In a limited study, selected suppository formulations were evaluated for efficiency of rectal absorption of testosterone in three male volunteers ranging in age from 25 to 30 years. Significant reductions in the ratios of urinary metabolites to free testosterone were observed with polyethylene glycol 1000, esterified (C10-C18) fatty acids, and theobroma oil-based samples. PMID- 8468683 TI - Epithelial transport of drugs in cell culture. VIII: Effects of sodium dodecyl sulfate on cell membrane and tight junction permeability in human intestinal epithelial (Caco-2) cells. AB - This study demonstrates how the common pharmaceutical wetting agent sodium dodecyl sulfate (SDS) increases the absorption of drugs and peptides across the human intestinal epithelium. First, an assay that could follow the reversible and irreversible time-dependent effects of SDS on the permeability of Caco-2 cell monolayers with high reproducibility was developed. SDS (0.40 mM) exposure for 20 min resulted in reversible absorption enhancement of mannitol (M(r), 182 g/mol), 1-deamino-8-D-arginine-vasopressin (M(r), 1071 g/mol), and polyethylene glycol (M(r), 4000 g/mol). A longer (2 h) exposure to SDS resulted in irreversible absorption enhancement. Second, transepithelial electrical resistance measurements (TEER) together with fluorescence and transmission electron microscopy were used to study the effects of SDS on epithelial integrity, cell membranes, intracellular calcium concentration, cytoskeleton, and tight junctions. The effect of SDS (0.40 mM) on epithelial integrity was immediate. A significant decrease in transepithelial electrical resistance measurements was obtained with 1 min after exposure to SDS that was concomitant with increases in the permeability of the apical cell membranes and intracellular calcium concentration. SDS shortened the microvilli of the cells and produced apical (but not basolateral) membrane wounds, actin disbandment, disorganization of the terminal web, and structural separation of the tight junctions. The absorption enhancement was not reduced after repair of the apical cell membranes, indicating that SDS enhances drug and peptide absorption across the intestinal epithelium by the paracellular pathway. PMID- 8468684 TI - Reduction of erythrocyte membrane permeability and protein binding of low molecular-weight drugs following glycoside derivitization. AB - The permeability of glycosides (salicin, arbutin, glycyrritin, p-nitrophenyl-beta D-glucopyranoside, p-nitrophenyl-beta-D-galactopyranoside, p-nitrophenyl-beta-D lactopyranoside, and p-nitrophenyl-beta-D-maltopyranoside) and their aglycons through human erythrocyte membrane was investigated. The transport rate of the glycosides through human erythrocyte membrane was slower than that of their aglycons. Glycosides with a disaccharide did not permeate the erythrocyte membrane; this observation suggests that the introduction of disaccharide to drugs gives rise to a significant decrease in the leakage of drugs through the erythrocyte membrane. The derivatives of glycosides encapsulated in erythrocytes were not released from these erythrocytes into the outer medium. The transport capacity of the glycosides was not influenced by the kind of suspending medium, but that of the aglycons was influenced by the medium. The glycosides bound to human serum albumin more weakly than their aglycons. Particularly, the glycosides were more difficult to displace from 7-anilinocoumarin-4-acetic acid (site III drug) than their aglycons, except for glycyrritin. PMID- 8468685 TI - Barrier function of human skin and human reconstructed epidermis. AB - The present study compares the stratum corneum of human skin and human reconstructed epidermis by histological examination as well as by estimation of water permeability. Measurement of the percutaneous absorption of benzoic acid, testosterone, and hydrocortisone revealed that under the same experimental conditions the reconstructed epidermis on de-epidermized dermis exhibits a barrier function with qualitative properties similar to that of normal skin: water and benzoic acid penetrate more rapidly than testosterone and hydrocortisone. Quantitatively, however, reconstructed epidermis is more permeable than normal human skin. This points to an impaired barrier function of the epidermis reconstructed in vitro. PMID- 8468687 TI - Prediction of skin permeabilities of diclofenac and propranolol from theoretical partition coefficients determined from cohesion parameters. AB - The cohesion parameters of diclofenac and propranolol were determined experimentally. The theoretical partition coefficient (Ps,v) was calculated from the activity coefficient (gamma) and the cohesion parameters of the solvent (delta 1 = delta v), solute (delta 2), and skin (delta s). By using the extended Hildebrand solubility equation, the potential energy of solute-solvent interaction in a given solution was considered to have the gamma value derived from solubility data of diclofenac and propranolol in ethanol-aqueous buffer. Values for experimental permeability coefficients (Kp), which were determined from flux and solubility, were compared with values for the respective Ps,v. For a solvent that consists of ethanol-aqueous buffer exhibiting cohesion parameters in the range of delta v = 18-24 (cal/cm3)1/2, the fluxes increased and the Kp decreased because of the similarity in cohesion parameters of these solvents to the solute. The difference between Ps,v and experimental Kp suggests that ethanol in the solvent affects the membrane and diclofenac and propranolol penetrate through the membrane, possibly solvated by ethanol. PMID- 8468686 TI - Synthesis and hypolipidemic activity of 4-substituted 1-acyl-1,2,4-triazolidine 3,5-diones in rodents. AB - A series of 4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones demonstrated potent activity in CF1 mice when administered intraperitoneally at 20 mg/kg/day, lowering both serum cholesterol and triglyceride levels significantly. The 4-(4 chlorophenyl)-substituted compounds demonstrated better hypolipidemic activity in rodents than 4-methoxy-, 4-nitro-, and 4-t-butylphenyl substitutions. Aryl and alkyl substitutions rather than benzoyl substitutions at position 4 demonstrated good hypocholesterolemic activity. Selected compounds were examined for the mode of action in rats in which serum cholesterol and triglyceride levels were reduced after administration of 20 mg/kg/day orally; tissue lipids were reduced after 14 days of administration, and bile and fecal lipids were increased by 44-250%. Serum lipoprotein levels were also modulated by the agents, with cholesterol levels in very low density lipoprotein and low density lipoprotein fractions being reduced by 2-57%. Cholesterol levels in the high density lipoprotein fraction were elevated by 94-341%. Activities of mouse hepatic enzymes were suppressed by the agents in a manner that suggested that the compounds interfere with de novo synthesis of lipids. PMID- 8468688 TI - Influence of albumin on the distribution and elimination kinetics of diclofenac in the isolated perfused rat liver: analysis by the impulse-response technique and the dispersion model. AB - The impulse-response technique was used to investigate the influence of changes in the perfusate concentration of human serum albumin (HSA; 1.5-25 g/L) on the distribution and elimination kinetics of [14C]diclofenac in the isolated perfused rat liver. Output data were analyzed by a linear systems approach in combination with the axial dispersion model of hepatic elimination. This stochastic model is characterized by a dimensionless parameter (the dispersion number, DN) that quantifies the relative spreading of a substance as it passes through the liver. The two-compartment form of the axial dispersion model, which assumes that the radial transfer of a substance between the vascular and cellular spaces proceeds at a finite rate, was used to describe the output profiles for diclofenac, thereby providing estimates for DN and the first-order rate constants for the transfer of drug between the vascular and cellular compartments (k12 and k21) and its sequestration from the cellular compartment (kel). With a change in perfusate HSA concentration, the only one of these parameters to alter significantly (analysis of variance, p < 0.05) was the uptake rate constant (k12), which increased from 0.091 +/- 0.016 (mean +/- standard deviation) to 0.79 +/- 0.09 s-1 as HSA decreased from 25 to 1.5 g/L. Most of this change could be accounted for by an increase in the fraction of diclofenac unbound in perfusate, from 0.0030 to 0.0407 as HSA decreased from 25 to 1.5 g/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468689 TI - Nonlinear pharmacokinetics and protein binding of tiaprofenic acid in female Lewis rats. PMID- 8468690 TI - Comments concerning "Solvent effects on chemical processes. I: Solubility of aromatic and heterocyclic compounds in binary aqueous-organic solvents". PMID- 8468691 TI - Transport of L-tryptophan across the rat nasal mucosa. PMID- 8468692 TI - Reduction of plantar pressure with the rigid relief orthosis. AB - The rigid relief orthosis was developed to protect vulnerable sites on the plantar surface of the insensitive foot against reulceration by providing both a nonyielding relief under the healed lesion site and a total contact fit. Clinically, the rigid relief orthosis has been effective in protecting the foot against the trauma induced by the repetitive mechanical stress of walking. This study used both the Hercules and F-Scan pressure transducer systems to measure pressure at the first metatarsal head in three orthotic treatments. Both measurement systems recorded significant reductions in pressure at the first metatarsal head with the rigid relief orthosis, establishing a quantitative rationale explaining its clinical effectiveness. Significant pressure differences were also recorded at the secondary sites of the heel, midfoot, and third metatarsal head. PMID- 8468693 TI - Current concepts in bone healing. Review of the literature. AB - Bone healing is a process of reconstitution of tissue. With the development of rigid internal fixation, primary bone healing has exhibited certain histologic characteristics not previously seen. The authors discuss the histologic, biochemical, and physiologic processes seen in primary and secondary bone healing following fracture or osteotomy. PMID- 8468694 TI - Anatomical basis for congenital deformities of the lower extremities. Part II. The knee and leg. AB - The congenital etiology of many malformations of the lower extremities is undisputed. This study uses cryomicrotomy of the knees and legs of midterm fetuses to establish the best anatomical representations of lower extremity parts, as they are developing, in a partially microscopic form. Adequate treatment plans of congenital defects require a knowledge of the normal status of development, and this investigation provides these data in a unique way. A comprehensive review of current therapeutic philosophies is related to morphology, which is discussed in light of the various congenital abnormalities of the knee and leg. PMID- 8468695 TI - Orthotic survey. Preliminary results. AB - A nationwide survey of patient satisfaction and effectiveness with prescription foot orthoses was conducted. Five hundred twenty patients were fitted with foot orthoses and evaluated for 14 weeks. The survey was not confined to a single medical condition. The level of patient satisfaction and the final fit of the custom-fitted orthoses were excellent. Effectiveness of the orthoses in the patient population ranged from 62.5% of the cases having the chief complaint completely resolved to 4.7% unresolved. Orthoses reduced or delayed the need for surgery in general and for hallux valgus and hammer toe specifically. Although several conclusions can be drawn on the basis of these survey results, this study highlights the need for a more detailed study and research into the prescription of orthoses to improve clinical practice, patient quality of life, cost effectiveness, and the design and manufacture of orthoses. PMID- 8468696 TI - Pathophysiology of diabetic neuropathy. AB - Angiopathy, immunopathy, and neuropathy are the key components responsible for diabetic foot complications. The authors report on the current theories of metabolic and structural causes of diabetic neuropathy. PMID- 8468697 TI - Cuboid stress fracture. A case report. AB - Because a stress fracture is rare and easily missed on an x-ray, it might go undetected. If a patient presents with an activity related injury to the midfoot and x-rays are negative, a computed tomography scan can be helpful in diagnosing a cuboid stress fracture. Also, computed tomography scans graphically show the fracture location and size, in addition to tracking progressive bone changes during the healing process. PMID- 8468698 TI - Neurologic disorders affecting the lower extremities in HIV infection. PMID- 8468699 TI - Ataxic gait. Complication of chicken pox. PMID- 8468700 TI - Heterotopic finger transfer in ulnar ray deficiency associated with contralateral postaxial polydactyly: a case report. PMID- 8468701 TI - Intraoperative histopathologic nerve examination in brachial plexus injury. AB - A new method of indirect intraoperative evaluation of axonal quality in a proximal nerve stump by immediate observation of the myelin sheath is presented. Using this method in 18 cases of brachial plexus injuries, the proximal stumps of particular roots or trunks were classified as unfavorable, favorable, or fair. This histologic grading was compared to the clinical result obtained after surgical repair of these nerves in the corresponding territory. In three cases, the proximal stump of the brachial plexus root was sacrificed because of an unfavorable grade, and a nerve transfer was performed: the results were useful in two cases and "academic" in one case. Among 12 cases with favorable histologic grades, nine were associated with useful function and three were "academic". Among three cases with a fair histologic grade, two were associated with an "academic" result and one was useful in a nine-year-old child. Retrospective comparison with classic examination after axon staining showed that intraoperative histopathologic grading was somewhat too optimistic in six cases and was relevant in 12 cases. This method may be helpful in choosing proper methods for brachial plexus repair. A normal or almost normal histopathologic condition in the proximal stump of the nerve is mandatory for obtaining a useful clinical result after repair. PMID- 8468702 TI - Microsurgical replantation of the avulsed scalp: report of six cases. AB - This article reports the successful microsurgical replantation of six scalps avulsed for over 3 to 11 hr, after trauma and before repair, including five total and one partial avulsion. The authors believe that one key to successful replantation is effective vessel anastomoses. In the reported series, three scalps were reconstructed with two superficial temporal vessels and in five cases, with a 1:1 ratio between arteries and veins. The partially avulsed scalp was replanted successfully with only one artery and one vein. The management of postoperative complications is discussed. PMID- 8468703 TI - The structural basis of Felice Fontana's spiral bands and their relationship to nerve injury. AB - In 1779, Felice Fontana, using a six-power hand-held magnifying lens, described what appeared to be spiral bands surrounding the peripheral nerve. He hypothesized that these bands were due to an optical illusion related to the underlying undulations of the individual nerve fibers, which he was the first to observe with an early microscope. The present study examines the historical basis of Fontana's work, confirms with intrafascicular dissection that the bands are an illusion created by unstretched nerve fibers, and relates their clinical disappearance to current concepts of the pathophysiology of chronic nerve compression and nerve injury. PMID- 8468704 TI - Direct muscle neurotization recovers gastrocnemius muscle function. AB - This case report describes a devastating injury in which a distal motor nerve had been avulsed from the muscle belly and was not available for reconstruction. This otherwise irreparable posterior tibial nerve injury was successfully treated by direct neurotization of the muscle belly. The patient did have one small, intact, muscular branch to the medial gastrocnemius muscle; however, electrodiagnostic and clinical examination and recovery pattern suggested the neurotization procedure was responsible for the functional recovery. In the rare situation where no distal nerve is available, and tendon transfers or arthrodesis are inappropriate, direct muscle neurotization can be considered as a salvage technique. PMID- 8468705 TI - Direct muscle neurotization. AB - The results of experimental research, as well as of a large clinical series (n = 51) of direct muscle neurotization, have been encouraging enough to warrant extending the indications for the procedure to patients in whom traditional repair by direct nerve suture or nerve graft is impossible, because of the lack of a distal nerve segment, or because of destruction of the neural portion of one or more muscle groups. Prerequisites include a satisfactory volume of muscle with sufficient vascularity and adequate postoperative joint and muscle immobilization. PMID- 8468706 TI - Microsurgical reconstruction in limb-salvage procedures: comparison between primary and secondary reconstruction. AB - Limb-salvaging procedures after malignant tumor resection in the extremities were performed in 22 cases, utilizing microsurgical tissue transplantation. Five patients had soft-tissue tumors and 17 had bone tumors. Thirteen cases were primarily and nine were secondarily reconstructed. The advantages and disadvantages of both primary and secondary reconstructions were compared: as to technical difficulty, primary reconstruction was much easier. Chemotherapy was necessary just before and/or after reconstruction in eight of 13 cases of primary reconstruction. Delayed union or non-union occurred more frequently in patients who required chemotherapy, but eventual union was achieved in all cases by adding a conventional bone graft. As for oncologic and functional status, there was no difference in oncological status between the primary and secondary groups, but the primary reconstructions showed better functional results. Although individualized treatment is of utmost importance when utilizing microsurgical reconstruction to save limbs, primary reconstruction can be done most successfully when there is a wide surgical margin after tumor resection and when attention is paid to the avoidance of such complications as delayed union or non union. PMID- 8468707 TI - Gender differences in factors associated with hypoactive sexual desire. AB - Several factors have been identified as playing an etiological role in hypoactive sexual desire. It has been assumed that these factors appear equally among men and women, however, there is little empirical validation for this. An investigation of 69 men and women was undertaken to explore whether certain medical, psychological, sexual, and/or interpersonal factors were more likely to present in men versus women. Significant differences were found with regard to age, psychological distress, relationship satisfaction, level of stress, and the duration of another sexual dysfunction. Implications for a refined understanding of hypoactive sexual desire and for treatment are discussed. PMID- 8468708 TI - The female androgen deficiency syndrome. AB - We evaluated the sexual functioning of 11 women who developed demonstrable androgen deficiencies after undergoing chemotherapy with cytotoxic agents and/or bilateral salpingo-oophorectomies for a variety of medical conditions. For comparison, we evaluated the sexual status of 11 subjects with comparable medical, menopausal, marital, and sexual histories, whose levels of circulating testosterone were within normal limits. The results of this clinical study confirm and extend the observations originally made by Waxenberg and his colleagues in 1959, that testosterone deficiency in women produces a marked decrease in libido and sexual responsiveness. Our findings further indicate that the female androgen deficiency syndrome is often indistinguishable from psychogenic desire disorders on clinical grounds alone. PMID- 8468709 TI - A comparative study using orgasm consistency training in the treatment of women reporting hypoactive sexual desire. AB - In an experimental study, a standard group intervention for treating women with hypoactive sexual desire was compared to a standard group intervention plus orgasm consistency training. Specificity of sexual change following treatment was assessed in 39 women with hypoactive sexual desire disorder who completed either treatment. Following treatment, women in both groups reported significantly positive sexual changes on two of the four measures of sexual behavior. Compared with the women receiving only standard treatment, the women who also received orgasm consistency training reported greater sexual arousal and sexual assertiveness at posttreatment and at three-month and six-month follow-up evaluations and greater sexual satisfaction at the six-month follow-up. Implications for these findings, study limitations, and future research directions are explored. PMID- 8468710 TI - Sexual functioning in HIV+ and HIV- injected drug-using women. AB - As part of a natural history study of HIV disease in injected drug users, 38 HIV positive (HIV+) asymptomatic or low-symptomatic women and 37 HIV negative (HIV-) women, mostly of minority inner-city background, underwent a comprehensive survey of sexual functioning. At study baseline, the sample as a whole showed a relatively high prevalence of problems in all major phases of the sexual response cycle and in vaginismus and vaginal pain. Statistically significant group differences indicate higher rates of problems in sexual functioning in HIV+ women even at an early stage of disease progression. PMID- 8468711 TI - The she-male phenomenon and the concept of partial autogynephilia. AB - The term autogynephilia denotes a male's propensity to be sexually aroused by the thought or image of himself with female attributes. Some autogynephiles imagine themselves, in their sexual fantasies, as complete women. Others, here called partial autogynephiles, imagine themselves with a mixture of male and female anatomic features, usually women's breasts and men's genitals. Partial autogynephiles evince a particular sexual interest in those individuals known in the vernacular as she-males. These are men, often involved in prostitution or pornography, who have undergone breast augmentation while maintaining their male genitals. Partial autogynephiles appear less likely to pursue surgical sex reassignment than gender-dysphoric men whose erotic self-image includes a vagina. Some patients with a persistent desire for women's breasts but no or conflicted desires to live as women full-time or undergo vaginoplasty may be pacified with mildly feminizing doses of estrogenic hormones. PMID- 8468712 TI - Patterns of exposure to sexually explicit material among sex offenders, child molesters, and controls. AB - The Meese Commission Report claimed exposure to sexually explicit material leads to sex offenses and recommended examining developmental patterns and pornography experiences of offenders. This second phase of our study examines developmental patterns and sexually explicit material experiences of sex offenders, a subgroup of child molesters, and controls. Results indicate sex offenders (but not the child molester subgroup) began masturbating at a significantly younger age than controls. Sexually explicit material was used during the first masturbatory experience of 33.3% of sex offenders and 14% of controls. Child molesters were significantly older than controls when exposed to sexually explicit material. Frequency of adult use of sexually explicit material does not differ significantly among groups. PMID- 8468713 TI - Suramin: here to stay!? PMID- 8468714 TI - Pesticide residues and breast cancer: the harvest of a silent spring? PMID- 8468715 TI - The Delaney clause: too much of a good thing? PMID- 8468716 TI - IARC publishes western Europe cancer maps. PMID- 8468717 TI - Optimal timing of breast cancer surgery: findings revive debate. PMID- 8468718 TI - Pro-tobacco group attempts to discredit EPA's announcement. PMID- 8468719 TI - Suramin, an active drug for prostate cancer: interim observations in a phase I trial. AB - BACKGROUND: Previous studies indicate that suramin may be an active agent for treatment of solid tumors. The clinical use of suramin is complicated by a broad spectrum of toxic effects and complex pharmacology. Studies have suggested that the dose-limiting neurotoxicity of this agent is closely related to sustained plasma drug concentrations of 350 micrograms/mL or more. PURPOSE: This phase I clinical trial in patients with solid tumors was designed to determine whether plasma concentrations resulting in both antitumor activity and manageable toxicity could be achieved with short, intermittent infusions of suramin. METHODS: Thirty-seven patients, including 33 with metastatic, hormone-refractory prostate cancer, collectively received 43 courses of suramin designed to maintain a plasma concentration range of 200-300, 175-275, or 150-250 micrograms/mL. Patients received a test dose of 200 mg and an initial loading dose of 1000 mg/m2 on day 1 of therapy. Subsequent suramin doses and schedules were individually determined using a strategy of adaptive control with feedback, which used a maximum a posteriori Bayesian algorithm to estimate individual pharmacokinetic parameters. Patients were treated until dose-limiting toxicity or progressive disease developed. RESULTS: Thirty-five of the 37 study patients and 31 of the 33 with prostate cancer were assessable for toxicity and response. Treatment was discontinued in 28 patients because of dose-limiting toxicity consisting of a syndrome of malaise, fatigue, and lethargy; recurrent reduction in creatinine clearance of 50% or more; or axonal neuropathy. Evidence of major antitumor activity was observed in patients with prostate cancer treated at all three plasma drug concentrations. Measurable responses (one complete response and five partial responses) were noted in six of 12 patients with measurable disease. Twenty-four (77%) of 31 patients had a reduction in prostate-specific antigen of 50% or more, and 17 (55%) of 31 had a reduction of 75% or more. Twenty (83%) of 24 patients reported reduction in pain. CONCLUSIONS: Suramin can be safely administered as an intermittent bolus injection by use of adaptive control with feedback to control plasma drug concentrations; toxicity is significant but manageable and reversible. Suramin is active against hormone-refractory prostate cancer. IMPLICATIONS: Future trials should address the role and necessary extent of therapeutic drug monitoring; the optimal plasma drug concentration range and duration of therapy; and the activity of suramin in combination with other agents, in earlier stages of prostate cancer, and in other tumor types. PMID- 8468720 TI - Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. AB - BACKGROUND: Treatment using interleukin-2 (IL-2) alone or in conjunction with lymphokine-activated killer (LAK) cells has been shown to mediate disease regression in selected patients with advanced cancer. PURPOSE: This prospective randomized trial was designed to determine whether the administration of LAK cells in conjunction with high-dose IL-2 alters response and survival rates, compared with those for IL-2 alone, in patients with advanced cancer. METHODS: The 181 patients who had metastatic cancer that had failed to respond to standard therapy or who had disease for which no effective therapy existed received treatment with high-dose IL-2 alone or with LAK cells plus IL-2. Both treatment groups were to receive the same dose of IL-2 administered according to the same schedule. IL-2 doses were omitted depending on the tolerance of the patient. Of the 181 patients, 97 had renal cell cancer and 54 had melanoma. RESULTS: Median potential follow-up was 63.2 months. There were 10 complete responses among the 85 assessable patients who received IL-2 plus LAK cells, compared with four among the 79 who received IL-2 alone. There were 14 and 12 partial responses, respectively. Complete response continues in seven patients at 50-66 months. The 36-month actuarial survival with IL-2 plus LAK cells was 31%, compared with 17% with IL-2 alone (two-sided P value [P2] = .089). A trend toward improved survival was seen for patients with melanoma who received IL-2 plus LAK cells, compared with those who received IL-2 alone (24-month survival: 32% versus 15%; 48-month survival: 18% versus 4%; P2 = .064 [corrected]). None of 26 patients with melanoma who received IL-2 alone are alive; five of 28 who received IL-2 plus LAK cells are alive, and three continue in complete response. No difference in survival was seen in patients with renal cell cancer in the two treatment groups. There were six treatment-related deaths (3.3%); three were due to myocardial infarction. Other toxic effects resolved by discontinuation of IL-2. Many toxic effects were related to increased vascular permeability induced by IL-2. CONCLUSIONS: Some patients with metastatic cancer have prolonged remission when they are treated with high-dose IL-2 alone or in conjunction with LAK cells. Our results suggest a trend toward increased survival when IL-2 is given with LAK cells in patients with melanoma, but no trend was observed for patients with renal cell cancer. IMPLICATIONS: As these studies continue, efforts are underway to develop improved immunotherapies using tumor-infiltrating lymphocytes (TIL) and gene-modified TIL. PMID- 8468721 TI - Acute lung injury following treatment with high-dose cyclophosphamide, cisplatin, and carmustine: pharmacodynamic evaluation of carmustine. AB - BACKGROUND: Therapy with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) plus autologous bone marrow transplantation has been extensively studied as treatment for patients with stage II or III breast cancer who have a 70% or greater risk of developing metastatic disease. This therapy is being used in a cooperative intergroup phase III clinical trial. In the cyclophosphamide cisplatin-BCNU regimen, cyclophosphamide and BCNU, but not cisplatin, have been reported to cause acute lung injury, suggesting that either cyclophosphamide or BCNU may contribute to this injury. PURPOSE: The purpose of this study was to analyze clinical and pharmacokinetic data from our ongoing phase II trials and to determine whether there is an association between BCNU pharmacokinetics and acute lung injury following cyclophosphamide-cisplatin-BCNU therapy. METHODS: We performed a retrospective study of 38 patients treated following induction therapy or relapse, 29 with stage II-IV breast cancer and nine with intermediate and high-grade stage III-IV non-Hodgkin's lymphoma. These patients received therapy with cyclophosphamide at a dose of 1875 mg/m2 daily as a 1-hour intravenous infusion for 3 days, cisplatin at 55 mg/m2 per day as a 72-hour continuous intravenous infusion, and BCNU at 600 mg/m2 as a 2-hour infusion immediately following completion of the cisplatin infusion. Data from analysis of blood samples were used to calculate pharmacokinetic parameters for BCNU, and acute lung injury was determined on the basis of pulmonary function test results and histologic examination of lung biopsy specimens. RESULTS: Our analysis showed that 20 (53%) of the 38 patients developed pulmonary injury following treatment. Twelve (60%) of the 20 had values for area under the curve (AUC) for BCNU concentration x time that exceeded 600 (micrograms/mL) x minute, whereas only two (11%) of the 18 without pulmonary injury had values above this level (P < .03). Thus, 12 (86%) of 14 patients with BCNU AUC greater than 600 (micrograms/mL) x minute developed lung injury. CONCLUSIONS: These results suggest that BCNU exposure greater than 600 (micrograms/mL) x minute is associated with increased risk of acute lung injury after cyclophosphamide-cisplatin-BCNU therapy and may be a major cause of pulmonary drug injury following this regimen. IMPLICATIONS: Strategies aimed at more uniform drug exposure or selective neutralization of chlorethylisocyanate, one of the two major hydrolysis products of BCNU, might reduce the incidence of acute lung injury following this regimen without major compromise of antitumor effect. PMID- 8468722 TI - Blood levels of organochlorine residues and risk of breast cancer. AB - BACKGROUND: Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1 trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. PURPOSE: This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. METHODS: We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. RESULTS: Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. CONCLUSION: In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. IMPLICATIONS: These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far reaching for public health intervention worldwide. PMID- 8468723 TI - Psychological impact of screening for familial ovarian cancer. AB - BACKGROUND: Psychological distress following false-positive results could constitute a substantial disadvantage of cancer screening. PURPOSE: The purpose of this prospective study was to evaluate the psychological impact of true negative and false-positive results in a high-risk group of women in a screening program to detect early familial ovarian cancer by ovarian ultrasound scan. The influence of coping style was also assessed. METHODS: Of 500 women who contacted the nationally advertised screening program, 302 received the scan and participated in the study. Before the screening, they were mailed a questionnaire concerning psychological state, coping style, and anxiety about risk of cancer. Transabdominal ultrasonography and transvaginal ultrasonography with color Doppler imaging were used to detect persistent ovarian lesions and changes in volume. Women were informed of any abnormality immediately and asked to return for another scan after 6 weeks. Those with a persistent ovarian mass were referred for hysterectomy and bilateral oophorectomy. The questionnaire was used to reassess psychological distress after the first ultrasound scan, after re scanning, and after surgery. RESULTS: The first scan showed negative results for 233 of the 302 women; 69 (23%) had abnormalities in ovarian morphology. Sixty four of the 69 had a second scan, with negative results for 32 and equivocal results for 12; 20 had surgery because the results of both scans were positive. None of the patients in the screening program were found to have ovarian cancer. After the first scan, psychological distress and worries about cancer were significantly reduced (P < .001) in the women who had negative results. Responses to positive results depended on the baseline coping style and the clinician's appraisal of malignancy potential at the time of the scan. Women who had information-seeking coping styles and those who were referred for surgery had higher levels of distress than other women. At follow-up, the anxiety scores of women who had positive results on both scans but negative results at surgery had returned to baseline levels. CONCLUSIONS: The findings suggest that false positive results in screening are associated with increased distress in the short term, but these adverse effects do not appear to be severe or persistent. Women who had surgery appeared to welcome the certainty that they could never develop ovarian cancer. IMPLICATIONS: The issue of continued surveillance needs to be addressed, since many women expressed the desire to have the scan repeated regularly. PMID- 8468724 TI - Pentostatin in prolymphocytic leukemia: phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group. AB - BACKGROUND: B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias are aggressive variants of chronic lymphoid leukemias. The small studies conducted to date have shown median survival durations of approximately 3 years for patients who have B-cell prolymphocytic leukemia and 7.5 months for those who have T-cell prolymphocytic leukemia, compared with about 8 years for patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, chemotherapy consisting of alkylating agents such as cyclophosphamide and chlorambucil combined with prednisone has achieved overall response rates of 50% to 70%, but this regimen has resulted in response rates of less than 25% in prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies. PURPOSE: This prospective phase II trial by the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer was performed to assess the activity and toxicity of DCF in prolymphocytic leukemia. METHODS: Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then every other week for three doses. Patients who had at least partial response received maintenance therapy once a month for a maximum of 6 months. Fourteen patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic leukemia, as evidenced by morphologic and immunologic criteria; three were previously untreated, eight had been given one or two chemotherapeutic regimens, and nine had been given more than two. RESULTS: One patient died of an unknown cause during the first 6 weeks of treatment, and one died of disseminated toxoplasmosis during the period of maintenance therapy, 5 months after achieving partial remission. Nine (45% response rate) of the 20 patients achieved partial remission, including seven (50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell prolymphocytic leukemia. The median duration of response was 9 months (range, 2 30 months); for patients with B-cell prolymphocytic leukemia, the median remission duration was 12 months. No complete remission was observed. Toxic effects included nausea and vomiting (30%), infections (30%), and transient increase in liver enzymes (35%) and in creatinine (20%) levels. Eight patients experienced thrombocytopenia, the major hematologic toxic effect; four had grade 3 or 4 toxic effects. CONCLUSION: DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens. IMPLICATIONS: Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia. PMID- 8468725 TI - Effect of high-protein diet on pyrimidine synthesis and response to PALA in mouse tissues. AB - BACKGROUND: High-protein diets have been found to protect mice from the lethal effects of cytotoxic pyrimidine analogues and to reduce the toxicity of the antipyrimidine fluorouracil (5-FU), but the biochemical explanation for these effects is not known. PALA potentiates the chemotherapeutic efficacy of 5-FU, and each of the two agents can produce dose-limiting intestinal toxic effects. We have shown that intraperitoneal infusion of ammonium chloride stimulates intestinal de novo pyrimidine synthesis. This stimulation with excess ammonia, which can also result from high-protein intake, is dependent on the presence of carbamoyl phosphate synthetase I, an enzyme in the liver and intestine but not in most tumors. These findings suggest that a high-protein diet can stimulate pyrimidine synthesis in the liver and intestine but leave it unchanged in tumor tissue. PURPOSE: The purpose of this study was to determine whether varying dietary protein causes pharmacologically relevant and preferential changes in de novo pyrimidine synthesis. METHODS: Mice were fed diets containing 18%, 35%, or 50% casein. Dietary effects on de novo pyrimidine synthesis were measured in the intestine, liver, and B16 mouse melanoma in mice treated with PALA and in untreated mice. De novo synthesis was measured by infusion of [15N]alanine into intact animals, determination of 15N incorporation into uracil by use of gas chromatography-mass spectrometry, and calculation of the fraction of the uracil nucleotide pool formed by de novo synthesis. RESULTS: In mice on a 50% casein diet (high protein), de novo pyrimidine synthesis increased substantially in the liver and intestine, compared with synthesis in mice receiving 18% casein. Increase in pyrimidine synthesis in B16 tumor tissue was negligible. The high protein diet protected the intestine and liver from depletion of uracil nucleotide pools by PALA, and toxicity in tumor-free animals was reduced, as determined by mortality after PALA treatment. Sensitivity of the B16 tumor to the biochemical and cytotoxic effects of PALA was not diminished. CONCLUSIONS: We propose that the basis for these effects of a high-protein diet is the generation of excess carbamoyl phosphate in tissues containing carbamoyl phosphate synthetase I. This carbamoyl phosphate can stimulate de novo pyrimidine synthesis and compete with drugs that interact with enzymes of the de novo pathway, thereby selectively protecting the liver and intestine. IMPLICATIONS: These data provide a biochemical explanation for reported effects of high-protein diet on toxicity of antipyrimidines like 5-FU. Studies are underway to determine if stimulation of pyrimidine synthesis by excess ammonia improves therapy with 5-FU alone or combined with PALA. PMID- 8468726 TI - Reversal by interleukin-2 of alopecia universalis, mucocutaneous candidiasis, and sexual impotence in a patient with malignant thymoma. PMID- 8468727 TI - Reduction in vasomotor symptoms from tamoxifen over time. PMID- 8468728 TI - Factor VIII-related antigen. PMID- 8468729 TI - The gastro-intestinal absorption of griseofulvin can be enhanced by encapsulation into liposomes. AB - Liposomes are microscopic structures consisting of one or more lipid bilayers enclosing a definite aqueous space. They are widely used as a drug carrier and for the delivery of drugs through membranes. Drugs can be encapsulated into the inner water phase or lipidic wall, depending on their own hydro- or lipophilicity. The characteristics of the vesicles is fusion with cells and natural endocytosis uptake. We applied the properties of liposomes to overcome the poor gastro-intestinal (GI) absorption of griseofulvin and compared results with the traditional dosage form. In this experiment, the maximum plasma concentration obtained from griseofulvin liposomes was about 2.6 times than that from griseofulvin suspension. We used the lipids to prepare liposomes that consisted of phosphatidycholine, cholesterol, and dicetylphosphate in the molar ratio, 1:1.6:0.2, which is similar to the membrane composition of red blood cells. We examined some factors affecting the encapsulation ratin (E.R.%) and physicochemical properties of liposomes. When the lipid-to-griseofulvin weight ratio approached 38:1, the encapsulation ratio reached 94%. The different lipid/aqueous ratio (19/1 48/1 96/1) appeared to have little effect on E.R. value. The stability of griseofulvin liposomes in terms of leakage of griseofulvin was negligible over a period of 18 days at 4 degrees C. The sedimentation of vesicles bearing negative charges exhibited the best flocculation state. The plasma level-time profile of griseofulvin obtained from ingestion of liposomal dosage form showed itself to be significantly higher (P<0.01) Cmax, AUC, Ka, and t1/2 than that from suspension. PMID- 8468730 TI - Total ankle replacement: preliminary report of 3 cases. AB - Total Ankle Replacement has been quite limited used currently and ankle arthrodesis is still the treatment of choice for most disabling arthritic disease of the ankle because of the generally poor long term results of ankle replacement. In spite of its popularity, ankle arthrodesis has many disadvantages, including long immobilization, high pseudoarthrosis rate, and load shift with increased stress on the neighboring joints of ankle. Total ankle replacement may be tried on some selected cases, such as on older patients or on patients with bilateral ankle lesions, multiple joints involved arthritis, such as rheumatoid arthritis etc. This paper reports three ankle replacements with a two year follow up, and they all have encouraging short term results. In the future, the development of a more effective ankle replacement seems to be likely. But at the present time, only carefully choosing the available prosthesis and strictly selecting the indicated patient can make the total ankle replacement acceptable. PMID- 8468731 TI - [A radiographic survey of root resorption in pulpless primary teeth]. AB - The goal of this article is to survey the relation between root resorption types and sex, age, pulpless source, tooth position of pulpless primary central incisors. Healthy children with pulpless primary maxillary central incisors were systematically selected from the Kaohsiung Medical College Hospital Pedodontic Department. After a complete recording of age (3-6y/o), Sex (male, female), pulpless source (caries, trauma), and tooth position (#51, #61), the bisecting angle technique was used to take periapical X-ray film of pulpless primary maxillary central incisors. A total of 112 pulpless primary central incisors was collected and classified into 5 types: Type I--mild resorption Type II--end cutting resorption Type III--semi-circumferential resorption Type IV- circumferential resorption Type V--irregular resorption 15 teeth (13.4%) were classified as type I, 27 teeth (24.1%) classified as type II, 35 teeth (31.2%) as type III, 30 teeth (26.8%) as type IV, and 5 teeth (4.5%) classified as type V. Chi-square analysis between root resorption types and sex, age, pulpless source, tooth position were performed, and two results were noted: (1) There are no relation between root resorption types and sex, age, tooth position. (2) There is a close relation between root resorption type and pulpless source. The pulpless teeth caused by caries tend to be resorbed as type III and type IV; on the other hand, the pulpless teeth caused by a traumatic source tend to behave like type I and type II. PMID- 8468732 TI - [A study of patient severity classification and nursing hours]. AB - The purpose of this study utilizing the patient classification system was to investigate the distribution of categories of patient severity in medical departments in relation to the nursing hours required for each patient according to the severity of illness. In addition, Work distribution among nursing personnel and evaluation for the feasibility of this program were also considered. As per a proto-type index, patient severity was recorded by the observer; a factor-type nursing requirement table was designed by the nursing personnel. There were 621 samples collected from sub-specialized medical departments. Snapshot observations were taken to survey the allocation of nursing care time. The total of 88 samples of nursing personnel data were analyzed. The results showed that most categories of patient severity were distributed among B II, B III, C III, C IV while the average nursing hours required daily fluctuated between 1.21-10.38 hours. Because of the few samples in A III, B IV, C II, the average nursing hours among three categories were no significance in statistics, and other categories were significant. The researcher may use the nursing hour model as an approach to determine ideal nursing manpower. PMID- 8468733 TI - Giant ectopic pelvic spleen: report of a case and review of the literature. AB - We report a case of giant ectopic pelvic spleen combined with an accessory spleen and confirmed by liver-spleen scan, angiography, magnetic resonance imaging, and surgical findings. In various reviews of the literature, no ectopic pelvic spleen larger than this one has been reported. PMID- 8468734 TI - The effect of adjuvant chemotherapy for nasopharyngeal carcinoma: a preliminary report. AB - In the past, radiation therapy was the main treatment modality in nasopharyngeal cancer, but recently, combined induction chemotherapy has become a trend. In this study patients with NPC were divided into two groups. In Group I, 46 cases were treated with chemotherapy (Cisplatin + 5-Fu) and radiation. In Group II, 49 cases were given radiation only. The side effects of chemotherapy were tolerable except for 2 dropouts due to intractable vomiting and semi-coma respectively. Only 17 cases got leukopenia and one case was graded I in BUN evaluation. All of the cases were within normal limits in the platelet and creatinine evaluation. Nine cases acquired hyponatremia. The response rate was 72.7% in the primary site which included 22.7% of the complete response and 50.0% of the partial response with a 80.0% response rate in neck site, which included 56.7% of complete response and 23.3% of partial response. But after the consecutive radiation, the differences of response rate did not show any significance between the two groups. The difference in the response rate between non-keratinizing and undifferentiated carcinoma were significant. PMID- 8468735 TI - Canadian Society of Otolaryngology--Head and Neck Surgery. 47th annual meeting. Victoria, British Columbia, 7-12 May 1993. Abstracts. PMID- 8468736 TI - Prenatal sonographic findings of trisomy 18: review of 47 cases. AB - Prenatal sonographic findings were reviewed in 47 consecutive fetuses with trisomy 18. One or more abnormalities, excluding choroid plexus cysts, were found in 39 fetuses (83%), including 21 of 29 (72%) fetuses examined between 14 and 24 weeks and all 18 (100%) fetuses examined after 24 weeks. Abnormalities most frequently detected before 24 weeks included cystic hygromas, nuchal thickening, and meningomyelocele. Intrauterine growth retardation, cardiac defects, and an enlarged cisterna magna were detected more frequently after 24 weeks than before 24 weeks (P < 0.05). Intrauterine growth retardation was the single most common abnormality, detected in 51% of all fetuses and 89% of fetuses examined after 24 weeks. Choroid plexus cysts were identified in 25% (12 of 47) of fetuses, including 11 of 29 (38%) fetuses seen before 24 weeks. Additional abnormalities were identified in 10 of 12 (83%) fetuses with choroid plexus cysts; one of the two remaining fetuses showed clenched hands and a cardiac anomaly at autopsy, and the other showed unusually large, multiple choroid plexus cysts. Awareness of the type of anomalies and the usual menstrual age of diagnosis in fetuses with trisomy 18 should improve patient counseling and prenatal detection of fetuses considered at risk for this disorder. PMID- 8468737 TI - Isolated tubal torsion: clinical and ultrasonographic correlation. PMID- 8468738 TI - Neonatal small bowel obstruction due to Meckel diverticulitis: diagnosis by ultrasonography. PMID- 8468739 TI - Skeletal muscle sonography: a correlative study of echogenicity and morphology. AB - In skeletal muscle sonography high echogenicities have proved to be of diagnostic value. The following study examines whether these echointensities are caused mainly by interstitial fat or fibrosis. Consequently, the echogenicities of 86 muscles, their diameters, and the thickness of subcutaneous fat layers superficial to these muscles were measured and compared for content of fat and connective tissue, which were assessed by morphometry and biochemical testing in the corresponding muscle biopsy samples. The results indicate that fat replacement constitutes the main cause of increased muscle echogenicity, whereas intramuscular fibrosis did not significantly affect the muscles' echogenicity. PMID- 8468740 TI - Duplex sonography of mammary tumors: a prospective study of 75 patients. AB - Seventy-five breast neoplasms have been examined with duplex sonography to establish the optimal threshold value of systolic peak flow velocity to differentiate benign from malignant tumors. It could be shown that a systolic peak flow of > or = 0.2 m/s (Doppler angle corrected to 0 degrees) provides the best relationship between sensitivity and specificity concerning characterization of tumors. However, the data we obtained indicate that only positive findings are potentially reliable. Negative sonographic results should not be used to conclude a lesion is benign. Additionally, a new algorithm for breast tumors in which duplex sonography is an integral part is discussed. PMID- 8468741 TI - Prospects for ultrasonic spectroscopy and spectral imaging of abdominal tissues. AB - A system for the digitization and frequency spectral analysis of radiofrequency data for ultrasonic waveforms backscattered from abdominal tissues is described. Studies of phantoms meant to simulate abdominal tissues of differing scattering characteristics indicated that frequency spectral differences due to differences in the frequency dependence of backscattering were seen with 5 MHz probes, but not with a 3.5 MHz probe. Studies of a phantom with a simulated lesion of altered scattering characteristics indicated potential for improved lesion detection and characterization, using custom circuitry developed for variable bandwidth filtering of received ultrasonic beams. The techniques discussed have potential for improved diagnosis of diffuse and focal abdominal abnormalities over that obtained with conventional ultrasonic imaging. PMID- 8468742 TI - Work in progress CAVUS: transcaval ultrasonography of abdominal organs. Preliminary results. AB - Endoluminal sonography using tiny transducers (20 MHz) has found wide application in various fields of investigation. We have applied the same technology to the assessment of abdominal organs using the transcaval route (CAVUS). Normal vessels and both normal and dilated bile ducts were displayed. Although the procedure is simple and safe, and the images produced are excellent, to be useful clinically, microtransducers (6 or 7 MHz) will have to be developed. This technique holds much promise, and further miniaturization will allow greatly expanded use of endoluminal approaches. PMID- 8468743 TI - Fetal syphilis: correlation of sonographic findings and rabbit infectivity testing of amniotic fluid. AB - Fetal syphilis is the presumed diagnosis when the sonographic findings of fetal hydrops are found in the presence of maternal syphilis. In the absence of fetal hydrops, the diagnosis of fetal infection is difficult. We hypothesized that intra-amniotic infection would be accompanied by anatomic placental and fetal abnormalities that could be detected by ultrasonography. Rabbit infectivity testing (RIT), intratesticular inoculation of rabbits with amniotic fluid, can be used to confirm intra-amniotic infection with Treponema pallidum. Twenty-one gravidas with untreated early (primary, secondary, and early latent) syphilis underwent sonography and amniocentesis for RIT at 24 weeks of gestation or later. Antenatal sonographic findings were compared to their amniotic fluid RIT results. Hepatomegaly was significantly (P < 0.01) associated with amniotic fluid infection detected by RIT. Antenatal detection of hepatomegaly, which is probably the initial sonographic manifestation of hydrops fetalis, may ultimately identify the fetus affected with congenital syphilis. PMID- 8468744 TI - What constitutes an expert witness? PMID- 8468746 TI - Survey suggests rise in health habit complacency. PMID- 8468745 TI - Clinicians' forensic interpretations of fatal gunshot wounds often miss the mark. PMID- 8468747 TI - Vaccine Program Advisory Committee sticks Secretary Lee with plan to fix vaccination system. PMID- 8468748 TI - FDA lifts ban on women in early drug tests, will require companies to look for gender differences. PMID- 8468749 TI - From the Centers for Disease Control and Prevention. False-positive serologic tests for human T-cell lymphotropic virus type I among blood donors following influenza vaccination, 1992. PMID- 8468750 TI - The cardiac risks of noncardiac surgery. PMID- 8468751 TI - The cardiac risks of noncardiac surgery. PMID- 8468752 TI - Echocardiography for diagnosis and management of rheumatic fever. PMID- 8468753 TI - Children from Romania: testing for tuberculosis. PMID- 8468754 TI - Health access America's coverage of detoxification. PMID- 8468755 TI - Beauty parlor stroke syndrome: report of five cases. PMID- 8468756 TI - Don Perlis and Jonathan: the Augenblick says phenylketonuria. PMID- 8468757 TI - Clostridium difficile colitis: causes, cures. PMID- 8468758 TI - Hip fractures and fluoridation. PMID- 8468759 TI - Clostridium difficile colitis: causes, cures. PMID- 8468760 TI - Clostridium difficile colitis: causes, cures. PMID- 8468761 TI - The treatment of Clostridium difficile colitis. PMID- 8468762 TI - The changing in-hospital mortality of women undergoing percutaneous transluminal coronary angioplasty. AB - OBJECTIVE: To compare in-hospital mortality among women and men undergoing percutaneous transluminal coronary angioplasty (PTCA) and determine whether mortality differences have changed recently. DESIGN: A retrospective cohort study. SETTING: Tertiary referral institution. PATIENTS: Consecutive series of 3557 patients (27% women) who underwent 4071 PTCA procedures. Two cohorts were analyzed: patients treated between 1979 and 1987 (n = 1970) and those treated between 1988 and 1990 (n = 2101). MAIN OUTCOME MEASURES: In-hospital and periprocedural mortality. RESULTS: Women were older than men (P < .001) and more had class III or IV angina (P < .001), unstable angina (P < .001), angina at rest (P < .001), cardiac failure (P < .001), and diabetes mellitus, hypertension, and hypercholesterolemia (P < .001). The PTCA was successful in 85% of women and 86% of men with an in-hospital mortality rate of 4.2% and 2.7%, respectively (P = .005). No significant change in mortality occurred in men between the early (2.2%) and late (3.1%) eras in contrast to a significant increase among women, 2.9% to 5.4% (P = .04). Periprocedural mortalities for women and men between 1979 and 1987 were 1.0% and 1.2% (P = not significant) and between 1988 and 1990 were 2.9% and 1.4% (P = .02), respectively. The multivariate odds ratio of in-hospital mortality for women vs men was 1.51 (95% confidence interval, 1.00 to 2.29; P = .05), although six other baseline variables were more powerful predictors of in hospital mortality. Accounting for body surface area resulted in no significant association between gender and in-hospital mortality. Periprocedural mortality was not independently associated with gender. CONCLUSIONS: In-hospital mortality among women has increased in recent years, but their higher mortality compared with men is related more to the severity of their underlying disease rather than gender alone. PMID- 8468763 TI - Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up. AB - OBJECTIVE: Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy. DESIGN: Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records. PARTICIPANTS: Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women. MAIN OUTCOME MEASURES: Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates. MAIN RESULTS: The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence. CONCLUSION: Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure. PMID- 8468764 TI - Medical interviewing and interpersonal skills teaching in US medical schools. Progress, problems, and promise. AB - OBJECTIVE: To assess educational practices, problems, and needs in the teaching of medical interviewing and interpersonal skills. DESIGN: Questionnaires sent to curricular deans and introductory course leaders at all US medical schools in 1991. RESULTS: Of 130 programs, 114 deans (88%) and 92 course directors (71%) responded. Respondents indicated some advances since a similar survey in 1977: Virtually all medical schools now offer teaching in medical interviewing and interpersonal skills. More faculty from a greater variety of disciplines are involved in this teaching. Most programs feature observation and feedback of students' interviews with patients, and use a variety of effective teaching methods, including simulated patients and role-playing, both little used in 1977. The majority of schools address students' personal growth through discussion or support groups. However, there are problems. Most schools lack a faculty development process. About half of the introductory courses on medical interviewing take place within physical diagnosis courses, often, it appears, without systematic observation, feedback, and evaluation of student skills. Many programs do not explicitly incorporate certain educational principles into their course designs. As in 1977, there appears to be little coordination or sequencing of teaching interpersonal skills throughout the curriculum in most medical schools. Most deans identified significant barriers to improving teaching. CONCLUSIONS: While a number of educational advances have occurred there is still great variation in the quality and intensity of courses offered in US medical schools. However, the pace of progress bodes well for the future. PMID- 8468765 TI - Side effects of glucocorticoid treatment. Experience of the Optic Neuritis Treatment Trial. AB - OBJECTIVE: To determine the incidence of side effects from short-term glucocorticoid therapy prescribed for treatment of optic neuritis in the Optic Neuritis Treatment Trial. DESIGN: Randomized, placebo-controlled, multicenter clinical trial. SETTING: Fifteen university- or hospital-based centers throughout the United States. PATIENTS: A total of 457 patients between the ages of 18 and 46 years with acute demyelinative optic neuritis were studied. INTERVENTIONS: (1) Intravenous methylprednisolone (250 mg every 6 hours) for 3 days while hospitalized followed by oral prednisone (1 mg/kg per day) for 11 days; (2) oral prednisone (1 mg/kg per day) for 14 days; and (3) oral placebo for 14 days. Each regimen was followed by a short taper. RESULTS: Only two patients experienced major side effects, psychotic depression in one and acute pancreatitis in the other. Both of these patients were from the intravenous methylprednisolone group and both of the side effects resolved without sequelae. Patients in both groups receiving active drugs more often reported sleep disturbances, mood change, stomach upset, and facial flushing and gained more weight during the treatment period than patients in the placebo group (P < .001 for each comparison). CONCLUSIONS: Although minor side effects are common, short-term glucocorticoid therapy in young, healthy adults is relatively safe. Because of the infrequency of serious side effects, outpatient administration of high-dose intravenous glucocorticoids may be feasible. PMID- 8468766 TI - Fraternity hazing revisited through a drawing by George Bellows. PMID- 8468767 TI - Court-ordered reimbursement for unproven medical technology. Circumventing technology assessment. AB - OBJECTIVE--Because we found examples where courts of law ruled against insurance carriers that had been sued for reimbursement for unproven medical procedures, we conducted a case study to determine the reasoning behind these decisions that run counter to accepted medical science. Such actions circumvent health technology assessment and could contribute to escalating health care costs and poorer quality health care. DATA SOURCES--A literature search identified 17 cases between 1980 and 1989 in which an insurance company was sued to reimburse a patient who had received an unproven or questionable health technology; 14 of these suits were decided in favor of the plaintiff, and the insurance company was ordered to pay. Discussed in this article are six of these cases, two involving Laetrile (amygdalin), two involving immunoaugmentative therapy, and two involving thermography, technologies that had previously been assessed as not safe, not effective, or inadequately evaluated. DATA SYNTHESIS AND CONCLUSIONS--The circumstances determining how the courts arrive at these "unscientific" decisions fall into three general categories: (1) for legal reasons, the insurance contract is interpreted in favor of the insured; (2) the reluctance and/or inability, legal or otherwise, of the courts to use published scientific literature; and (3) the use of adversarial "expert" witnesses with potential conflicts of interest. To address this situation, we first urge the legal and insurance industries to cooperate in improving the contract language and process in a way that would be both legally and scientifically appropriate. Second, we encourage the courts to use and foster the use of published peer-reviewed scientific material as evidence whenever possible. Third, we recommend that the courts choose their own unbiased expert witnesses to interpret scientific material. PMID- 8468768 TI - Regional effects and mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome. AB - OBJECTIVE: To test the hypothesis that positive end-expiratory pressure (PEEP) prevents the collapse of a given lung region when it is equal to or greater than the hydrostatic pressure superimposed (SPL) to that region. DESIGN: Intervention study with sequential levels of PEEP applied in random order to a cohort of patients with adult respiratory distress syndrome (ARDS). SETTING: Referral center for ARDS in a university hospital. PATIENTS: Ten ARDS patients (with Murray scores > 2.5). INTERVENTION: Basal computed tomographic (CT) section taken at 0, 2, 4, 5, 6, 8, 10, 12, 14, 15, and 20 cm H2O PEEP. MAIN OUTCOME MEASURES: Basal lung CT sections were divided into 10 equal levels from the ventral to dorsal surfaces. In each level SPL was measured from density and height. The inflation of the level was measured as the gas/tissue ratio (g/t); g/t changes with PEEP were defined as the g/t-P curve. The slope of the g/t-P curve was defined as level compliance (ie, the ratio of change in the g/t of the level to the change in pressure). A linear g/t-P curve was the criterion to detect inflation without recruitment (ie, new pulmonary units opening at a given pressure). A biphasic g/t-P curve (change of compliance after an inflection point) was the criterion to detect recruitment. Pflex was defined as the pressure at which the inflection point occurred. RESULTS: The SPL increased from level 1 (ventral) to level 10 (dorsal) (r = .91; P < .01). The number of linear g/t-P curves decreased from level 1 to level 10 (r = .98; P < .01), while the number of biphasic g/t-P curves increased (r = .95; P < .01). The Pflex increased from level 1 to 10 (r = .97; P < .01) and Pflex was similar to SPL (Pflex = 1.05 + 0.9 SPL; r = .75; P < .01). CONCLUSIONS: The increased SPL causes compression atelectasis; this is prevented when PEEP to a given lung region is equal to or greater than the SPL. PMID- 8468769 TI - Ventilatory management of respiratory failure in asthma. PMID- 8468770 TI - Futility and avoidance. Medical professionals in the treatment of obesity. PMID- 8468771 TI - The ARDS lung. New insights from computed tomography. PMID- 8468772 TI - Albert Bruce Sabin. PMID- 8468773 TI - [Effects of isoflurane, sevoflurane and enflurane on median nerve somatosensory evoked potentials in humans]. AB - Median nerve somatosensory evoked potentials (SEPs) were recorded over neck (N13) and scalp (N20) in 18 neurologically normal subjects anesthetized with isoflurane, sevoflurane or enflurane for abdominal or lower limb surgery. SEP recordings were made at 0.5, 1.0 and 1.5 MAC of each volatile agent without nitrous oxide. These three agents did not change N13 latency and amplitude. Increasing concentrations of isoflurane and sevoflurane were associated with graded reductions in N20 amplitude and increases in N20 latency and N13-N20 interpeak latency. During enflurane anesthesia N20 amplitude was smaller than that at increased in dose related manner. At 1.0 MAC of enflurane N20 amplitude was smaller than that at 0.5 MAC, but further decrease was not produced at 1.5 MAC. The data suggest that effects of sevoflurane on SEPs were more similar to those of isoflurane than those of enflurane. PMID- 8468774 TI - [A graphic presentation of the anesthesiologist's action pattern]. AB - The action patterns of anesthesiologists are different among individuals. We have developed a graphic presentation system for anesthesiologists' action patterns using computer graphics. The resulting representation is called "thought map". Data were obtained from 6 anesthesiologists (4 certified instructors and 2 new doctors) with a time interval of 2 years, regarding the use of 3 drugs (enflurane, sevoflurane and isoflurane). The "maps" were compared among individuals, dates and drugs. The following results were obtained: 1) significant differences existed among individuals, 2) during the 2-year time interval, 2 new drugs were introduced and the practice pattern alterations were seen in the maps, 3) for the 2 new anesthesiologists, the maps show the process of professional knowledge acquisition. We propose an index ("immovable rate"), denoting the proportion of the map where concentration of the drug didn't change. This index is to be used for evaluating human thinking. PMID- 8468775 TI - [Excessive nitrous oxide exhalation by postoperative patients in the recovery room]. AB - Expired nitrous oxide from patients in the recovery room is considered to be the major source of air pollution. We measured expired concentrations of nitrous oxide in three patients and three volunteers. After only 5 minute inhalation of 50% nitrous oxide, it took over 2 hours for exhaled N2O concentration to decrease to 25 ppm in volunteers and after 30 minute inhalation, it took over 4 hours. The patients inhaled 50% nitrous oxide for 60, 165, 150 minutes, respectively and all patients expired nitrous oxide, the concentrations of which exceed 100 ppm over 3 hours. As to the patient who inhaled nitrous oxide for 150 minutes, expired nitrous oxide over 25 ppm was detected 10 hours after the end of anesthesia, and it was 4 ppm even after 20 hours. Any personnel including anesthesiologists and nurses working in the operating room can be exposed to high concentrations of nitrous oxide exceeding the permissible limit of 25 ppm, whenever they take care closely of their patients. We do not have any effective measures to protect us from this kind of air pollution except employing total intravenous anesthesia. PMID- 8468776 TI - [Effects of sevoflurane on left ventricular diastolic function using transesophageal echocardiography]. AB - The effects of sevoflurane on left ventricular diastolic filling were evaluated using transesophageal Doppler echocardiography in 10 normal subjects. The time velocity integral of early filling decreased significantly with sevoflurane 1 MAC (7.73 +/- 2.05 to 6.82 +/- 1.90 cm), suggesting impaired left ventricular relaxation. Abnormal left ventricular relaxation results in compensatory increment of peak velocity and time-velocity integral during atrial filling, both of which were significantly decreased by sevoflurane in this study (35.5 +/- 6.6 to 29.1 +/- 4.8 cm.sec-1, 3.22 +/- 0.65 to 2.73 +/- 0.67 cm, respectively). Although the ratio of early peak velocity to late filling velocity was unchanged, it appears that left ventricular diastolic function including active relaxation, passive compliance, atrial contraction, and elastic recoil was impaired by sevoflurane 1 MAC. PMID- 8468777 TI - [Changes in heart rate during and after enflurane-nitrous oxide anesthesia]. AB - Changes in heart rate of 21 patients who received enflurane-nitrous oxide anesthesia were studied. They had no cardiac, pulmonary, nervous system and endocrine diseases. We measured coefficient of variation of R-R intervals (CV) and power spectrum of heart rate fluctuation in 6 periods, (1) control phase (the day before operation), (2) during operation under enflurane-nitrous oxide anesthesia, (3) ten minutes after endotracheal extubation, (4) sixty minutes after arrival in the recovery room, (5) the next morning and (6) the next evening. The patients who were 15-25 years old, showed larger value of CV and larger power of low frequency component (0.03-0.1 Hz, LFC) as well as high frequency component (0.2-0.45 Hz, HFC) compared with patients who were 40-50 years old during control phase. They showed a significant decrease of CV, LFC and HFC in period (2), (3) and (4) but not in (5) and (6). These evidences show that autonomic nervous system is impared after enflurane-nitrous oxide anesthesia until the next morning. PMID- 8468778 TI - [The plasma concentration of buprenorphine during its continuous epidural infusion after catheterization at different vertebral levels]. AB - We investigated 27 patients undergoing elective surgery under epidural anesthesia. The plasma concentration of buprenorphine during its continuous epidural administration was measured by the radioimmunoassay method. We also performed a retrospective study on supplemental analgesics necessary for 48 hours after surgeries. The plasma concentration of buprenorphine was found to be stable at 300 pg.ml-1 during its continuous epidural infusion. The frequencies of administration of supplemental analgesics were 3.3 times with catheterization at upper thoracic vertebral level, 2. 1 times at lower thoracic vertebral level and 1.7 time at upper lumbar vertebral level. We conclude that analgesia with the continuous epidural administration of buprenorphine is satisfactory at low plasma concentration and is superior, considering the necessity of supplemental analgesics to other methods of systemic administration. It is estimated that the epidural distribution volume at lower thoracic and upper lumbar vertebral level is twice the volume at upper thoracic level from plasma buprenorphine concentration. PMID- 8468779 TI - [The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass]. AB - The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass (CPB) were investigated in 16 patients undergoing elective open heart surgery under CPB. They were divided into 2 groups; high (25%) (H) and low hematocrit (15%) (L) groups according to the hematocrit values during CPB. Simultaneous measurements of blood flow velocity in the middle cerebral artery (VMCA) and oxygen tension in the jugular venous bulb (PjvbO2) were performed at prebypass, bypass, and post bypass periods. There were no significant differences in nasopharyngeal temperature (NPT), cerebral perfusion pressure, pump flow rate, and PaCO2 between the two groups at any period. VMCA changed in correlation with NPT in both groups, and VMCA in the L group was faster than that in the H group at any period. PjvbO2 increased during aortic cross clamp, and decreased on rewarming in both groups. However, there were no significant differences in VMCA and PjvbO2 between the two groups at any period. These findings suggest that increased cerebral blood flow may compensate the decreased oxygen content due to the hemodilution during CPB. Therefore, the profound hemodilution up to 15% of hematocrit is considered to be a safe technique during CPB. PMID- 8468780 TI - [Arterial blood ketone body ratio and systemic hemodynamics in patients with acute hepatic blood flow occlusion]. AB - This study was undertaken in order to clarify the influence of acute hepatic blood flow occlusion on arterial blood ketone body ratio (AKBR) and systemic hemodynamics. Ten patients for hepatectomy were divided into two groups. Group I was composed of five patients who had clamping of total hepatic blood flow (Pringle's method), and Group II was composed also of five patients who had clamping of the right hepatic artery and portal vein during operation. Ten minutes after clamping blood flow, AKBR decreased significantly in both groups, and a marked reduction in AKBR was observed in group I. During occlusion, cardiac output was reduced significantly, and immediately after declamping, mean arterial blood pressure and systemic vascular resistance index (SVRI) decreased significantly. These changes in hemodynamics in group I were larger than those of the other group. A larger reduction in AKBR was observed during occlusion, and the greater change in SVRI appeared after declamping blood flow. These findings suggest that in the cases with hepatic blood flow occlusion, especially total occlusion, a special attention should be paid to mitochondrial liver dysfunction and hemodynamic changes associated with acute hepatic blood occlusion. PMID- 8468781 TI - [The significance of arterial redox potential measurement by Vincent's method in evaluating the hemorrhagic shock state of rabbits]. AB - Previously we suggested that the arterial redox potential (ARp) is one of the most reliable indicators to evaluate the severity and outcome of the acutely-ill patients. In this study we attempted to clarify which redox system, intracellular or extracellular, is mainly represented by redox potentials measured from arterial blood in the hemorrhagic shock state rabbits. The arterial pyruvate/lactate, acetoacetate/beta-hydroxybutyrate and oxidized glutathione/reduced glutathione (GSSG/GSH) ratios were measured in hemorrhagic shock rabbits, and correlations between ARp and each of these factors were analyzed. The best correlation was found between ARp and P/L ratio. This indicates that ARp well reflects the cytosolic redox state, i.e. cytosolic [NAD+]/[NADH], and also [ATP]/[ADP][Pi] theoretically. The ARp is a valuable index in evaluating the shock state and can be easily measured with Vincent's method. PMID- 8468782 TI - [Blood gas changes during hypotensive anesthesia induced by prostaglandin E1]. AB - The influence of prostaglandin E1 (PGE1) on PaO2 at doses that produced slight hypotension was evaluated in 176 patients scheduled for surgery. When systolic blood pressure was stabilized after induction of anesthesia, PGE1 infusion was started until 20% reduction of systolic blood pressure was achieved. Arterial blood gases were analyzed before infusion of PGE1 and 30 min after the completion of this hypotensive level respectively. The reductions in both PaO2 [from 177 +/- 64 mmHg to 164 +/- 65 mmHg (mean +/- SD) (P < 0.01)] and PaO2/FIO2 [from 486.5 +/ 144.4 to 437.6 +/- 121.6 (P < 0.01)] were observed with PGE1 infusion of 0.079 +/- 0.068 micrograms.kg-1.min-1. The results of this study show that PaO2 decreases during induced hypotension with PGE1 infusion, but this decrease is not clinically significant. PMID- 8468783 TI - [Blood gas changes during laparoscopic cholecystectomy--comparative study of N2O pneumoperitoneum and CO2 pneumoperitoneum]. AB - During laparoscopic cholecystectomy by alternative insufflation of nitrous oxide and carbon dioxide, the changes of blood gas tensions were measured and analyzed in 12 patients. During N2O insufflation, PaO2 decreased by about 25 mmHg and PaCO2 was unaltered compared with the values before pneumoperitoneum. While during CO2 insufflation, PaO2 decreased by about 13 mmHg and PaCO2 increased by about 6 mmHg. We considered that decrease in PaO2 during N2O insufflation was associated with not only uneven ventilation/blood flow ratios but also with the reduction in the alveolar O2 tension caused by the diffusion of N2O absorbed from the peritoneum. PaCO2 increases during CO2 insufflation because CO2 is absorbed from the peritoneum, and is not excreted entirely through the lungs. PMID- 8468784 TI - [Plasma potassium concentrations during N2O-enflurane anesthesia in patients on chronic hemodialysis]. AB - Plasma potassium concentrations during anesthesia with N2O and enflurane in O2 were measured in 12 patients on chronic hemodialysis (HD) who underwent HD for about 2 hours just before anesthesia. Pre-HD and pre-anesthetic plasma potassium concentrations were 5.0 +/- 0.2 and 4.3 +/- 0.2 mEq.l-1, respectively. The potassium levels decreased slightly following induction of anesthesia, but increased significantly during and after surgery; and at the end of anesthesia the levels were similar to those measured just before HD. None of the patients developed acidosis, hypoxia or hypercapnia. Based on our results, we consider that plasma potassium levels should be measured frequently during surgery in patients who have high potassium levels just before HD and are subjected to HD just before anesthesia, because hyperkalemia may occur. PMID- 8468785 TI - [Reduction of the amount of perioperative blood transfusion by autotransfusion techniques in valvular heart surgery]. AB - We used autotransfusion in valvular heart surgery and evaluated its effect on perioperative homologous blood requirements. Methods of autotransfusion we used were intraoperative blood salvage using Cell Saver 4 and retransfusion (IAT), postoperative autotransfusion of shed mediastinal blood (PAT), and hemodilutional autotransfusion (HAT). The patients undergoing valvular heart operations were divided into three groups; group 1 (control group), group 2 (using IAT and PAT group), and group 3 (using IAT, PAT, and HAT group). Perioperative homologous blood requirements significantly decreased in group 3 compared to group 1 and group 2. Operations without homologous blood transfusion significantly increased in number in group 3 compared with group 1. In conclusion, autotransfusions described above were useful blood conservation techniques in valvular heart surgery. PMID- 8468786 TI - [An application of multiple logistic regression analysis to an outcome study on surgery for patients with femoral neck fracture]. AB - Sixty five patients with femoral neck fracture were examined to find any risk factor for their postoperative complications. Here, postoperative complications included cardiac catastrophe, pulmonary embolism, central nervous system accident, and respiratory failure requiring mechanical ventilation during the period of one week after operation. Multiple logistic regression analysis was used to predict these factors. Explanatory variables were selected based on the clinical judgement. Those variable are age, sex, preoperative underlying cardiac disease, preoperative underlying respiratory complications, the use of cement for the procedure, and anesthetic technique. The analysis revealed that the sex was the only variable that was considered significant based on the P value less than 0.05. However, multi-colinearity between variables was suspected to exist based on the correlation matrix analysis which may indicate that the factor is not, in fact, significant. In short, further study will be required to find any significant variables or risk factors to predict the outcome of untoward events. PMID- 8468787 TI - [Perioperative pulmonary thromboembolism. A clinical study]. AB - Pulmonary embolism (PE) is a major catastrophe during postoperative period. We had six patients who developed PE after surgery and one during anesthesia and surgery. Severe arterial hypoxemia (PaO2 41 +/- 14 mmHg) occurred in all six postoperative patients, but not in a patient who developed PE under anesthesia. In 3 patients with pulmonary artery catheter in place, pulmonary arterial pressure (PAP) increased significantly during the embolic events. PAP tended to decrease before the apparent improvement of PaO2 in each patient. This suggests that increases in anastomotic bronchial blood flow occurred following the events. In a patient who developed PE under enflurane-N2O-O2 anesthesia, neither hypoxemia nor hypotension occurred despite significant increase in PAP. All patients received heparin and urokinase intravenously, which caused persistent bleeding in two patients. It remains for further investigations to study the mechanisms of serious hypoxemia in postoperative patients with PE as well as those of favorably maintained pulmonary oxygenation in a patient with PE under general anesthesia. PMID- 8468788 TI - [The anesthetic management of Arnold-Chiari malformation with spinal cord injury]. AB - A rare case of spinal cord injury at C3 level associated with Arnold-Chiari malformation is reported. A 33 year old male was admitted with a complaint of walking difficulty. MRI revealed cerebellar herniation, and a plain X-ray showed spinous process adhesion of C2-3 and slight scoliosis. Percent vital capacity was reduced to 69%, and blood cell count showed a slight anemia. The patient was anesthetized for an orthopedic surgery with pethidine 70 mg, thiamylal 200 mg, 60% nitrous oxide, 40% oxide, and 0.5-1.2% isoflurane. There was a mild decrease in arterial blood pressure during surgical procedures, but this could be easily treated by fluid therapy, and there was no episode of autonomic hyperreflexia. Postoperative course of the patient was uneventful, except a transient pneumonia and urinary tract infection. The key in the anesthetic management of Arnold Chiari malformation with spinal cord injury is the control of intracranial pressure, care for respiratory dysfunction and the prevention of infection as well as autonomic hyperreflexia. PMID- 8468789 TI - [Accidental subdural catheterization discovered after postoperative respiratory depression]. AB - A 65-year-old man scheduled for gastrectomy was anesthetized with nitrous oxide combined with continuous epidural lidocaine. At the end of the operation, morphine 2 mg diluted in 0.25% bupivacaine 5 ml was injected through the epidural catheter. Seventy minutes later, the patient developed life-threatening respiratory depression which was antagonized by naloxone. The patient requested no analgesic during the first 26 postoperative hours. The respiratory depression in this patient was assumed to be caused by epidural morphine. Then subdural catheterization was confirmed radiologically. This was discovered to have resulted from migration of the epidural catheter into the subdural space. Subdural injection of morphine may have resulted in higher cerebrospinal fluid levels than the levels obtained after epidural injection. Subdural catheterization is a complication of epidural anesthesia that probably occurs more frequently than previously recognized. In postoperative patients receiving epidural morphine, their respiratory status should be monitored closely for hours. PMID- 8468790 TI - [Beneficial effect of bromocriptine in a patient with malignant syndrome and hepatic dysfunctions]. AB - A 39 year-old male, diagnosed as meningoencephalitis, was admitted because of the development of malignant syndrome. This syndrome appeared to have resulted from anti-psychotic drugs given to relieve excitement and insomnia. As he had hepatic dysfunctions, we could not administer dantrolene further. Therefore, we gave bromocriptine to ameliorate the symptoms such as muscle rigidity or hemodynamic perturbations. Thereafter, the patient gradually became stable in hemodynamics and in other symptoms. In addition, a further deterioration in hepatic functions did not occur with administration of bromocriptine. The case suggests that in patients with malignant syndrome associated with hepatic dysfunctions, bromocriptine could be a first choice as a pharmacological treatment of the syndrome. PMID- 8468791 TI - [A case report of total intravenous anesthesia for renal transplantation]. AB - A 20-year-old female patient with chronic renal failure received renal transplantation under total intravenous anesthesia with droperidol, fentanyl and ketamine. Anesthesia was induced with droperidol 12.5 mg, fentanyl 100 micrograms, ketamine 100 mg and vecuronium bromide 5 mg, and maintained with fentanyl and ketamine. Ketamine was given continuously at a rate of 2.0 mg.kg-1.h 1. After the renal artery and vein of the donor kidney were anastomosed with the patient's internal iliac artery and vein, the urine output of 7.7 ml.min-1 was obtained. The patient recovered from anesthesia smoothly and her postoperative course was uneventful. Although plasma epinephrine, cortisol and ADH levels showed significant changes during anesthesia mainly due to surgical stress, they returned to normal values after the end of operation. We conclude that this method of anesthesia would be a choice for renal transplantation. PMID- 8468792 TI - [Removal of a bronchial foreign body in a child using the laryngeal mask]. AB - The laryngeal mask (LM) was employed for the removal of a bronchial foreign body (screw) in a 2-year-old boy weighing 16 kg since the 6.0 mm external diameter fiberoptic bronchoscope (FBS) for extraction forceps could not be used under tracheal intubation. Anesthesia was induced with sevoflurane in 100% oxygen. After injection of fentanyl 25 micrograms and vecuronium 2 mg, a gastric tube and a size 2 LM were inserted. Throughout the extraction procedure by the FBS in the left main bronchus, the boy had one lung ventilated manually. The airway pressure was kept under 15 cmH2O to avoid gas leakage around the cuff and gastric inflation. Oxygen saturation of 100% with pulse oximetry and PETCO2 of 35 to 45 mmHg with capnometry were maintained. The foreign body was extracted by biopsy forceps. A Fogarty catheter was not effective because the balloon tip was broken by the screw. The LM does not prevent regurgitation and does not provide adequate ventilation under increased airway pressure, but it facilitates the use of a larger size FBS equipped with a variety of extraction forceps. Therefore, it seems to be a useful device for the removal of bronchial foreign bodies in children. PMID- 8468794 TI - [Cerebral blood flow velocity and electroencephalogram for the evaluation of intraoperative brain function during intrathoracic hyperthermia]. AB - It is well known that progressive hyperthermia exerts fatal damage on the human body. However, there have been few reports on the brain function or the means to provide adequate monitoring during hyperthermia. The purpose of this study was to introduce two new devices, the Life Scan electroencephalogram (EEG) Monitor (Neurometrics) and the TC2-64 (EME) transcranial Doppler sonography (TCD), both for monitoring brain function during hyperthermia. The Life Scan uses aperiodic analysis, which maps each waveform in relation to its frequency, amplitude, and time of occurrence rather than averaging a large number of waveforms over a given period. The Life Scan shows 80% of the whole amplitude of each wave as the activity edge (AE). The flow velocity of the middle cerebral artery was measured by TCD during hyperthermia. After the induction of modified neuroleptanesthesia (fentanyl and midazolam), AE was maintained at 11 Hz. With an increase in body temperature, AE gradually showed a trend toward a slow wave, though the slowing of EEG was interrupted when the patient awoke to slight stimulation. Therefore, it is speculated that the slowing of EEG in this case was caused by fentanyl. The mean cerebral blood flow velocity increased slightly from 28 to 32 cm.sec-1 by hyperthermia. It is concluded that the adoption of EEG and TCD was useful in determining the intraoperative cerebral function during hyperthermia. PMID- 8468793 TI - [An emergency operation for a Jehovah's Witness with ruptured thoracic saccular aneurysm]. AB - A 49-year-old male "Jehovah's Witness" was transferred to our hospital with hypotension, abdominal pain, and abdominal distension, and a diagnosis of ruptured thoracic saccular aneurysm was made. He and his family insisted on having an emergency operation for his ruptured aneurysm without blood transfusion. After an intensive discussion among the patient, his family, surgeons, and the director of the hospital, we performed the operation without blood transfusion. The operation using cardiopulmonary bypass took about five hours under enflurane anesthesia, but he died of circulatory collapse fifteen hours after the end of operation. As there may be various opinions concerning how we should take care of Jehovah's Witness patients, we have to manage them case by case. PMID- 8468796 TI - [Proceedings of the 79th annual meeting of the Japanese Society of Gastroenterology. Kyoto, March 29-31, 1993. Abstracts]. PMID- 8468795 TI - [A newly devised endotracheal tube for patients with narrowed trachea]. AB - A 27 year old female patient with pulmonary adenoid cystic cancer was planned for emergency tracheotomy for hemoptysis and severe dyspnea. Six month previously she had a silicon tube (5.5 mm-ID, 40 mm in length) placed in her trachea, because of severe tracheal stenosis. Airway management by endotracheal intubation was deemed necessary during the tracheotomy. However, because of her tracheal narrowing, it was not possible to insert a usual endotracheal tube for adult. First, we made a 4.0 mm-ID endotracheal tube without cuff 12 cm in length (TUBE 1), and a 5.5 mm ID tube 18 cm in length (TUBE 2). We inserted the TUBE 1 into the TUBE 2, and glued them with Aron-Alpha, making it 25 cm long. We could perform tracheotomy by intubating and wedging this tube into silicon tube. PMID- 8468797 TI - [Evaluation of coronary artery disease by 99mTc-PPN1011: comparison with 201Tl imaging and ventricular function]. AB - To evaluate clinical value of 99mTc-1,2-bis[bis (2 ethoxyethyl)phosphino]ethane(99mTc-PPN1011) imaging for assessing coronary artery disease (CAD), 99mTc-PPN1011 SPECT imaging at post-exercise and at rest was compared with 201Tl SPECT imaging at post-exercise and 3 hours in 24 patients with CAD. The sensitivities for detecting CAD were 100% (21/21) by 99mTc-PPN1011 SPECT and 95% (20/21) by 201Tl SPECT. The sensitivities for detecting stenosed coronary arteries (> or = 75% stenosis) were similar between 99mTc-PPN1011 (68%) and 201Tl (66%). The similar specificity values were obtained by 99mTc-PPN1011 (80%) and 201Tl (77%). The patterns of abnormality (normal, ischemia and scar) were concordant between 99mTc-PPN1011 and 201Tl images in 20 of the 24 cases (83%) and 106 of the 120 segments (88%). In the simultaneous analysis of cardiac function by first pass radionuclide angiography with 99mTc-PPN1011, there was good correlation between left ventricular ejection fraction and perfusion score at rest (r = 0.70) and exercise (r = 0.80). The degrees of abnormality between perfusion and wall motion were similar in 56 of 66 segments (85%) at rest and 52 of 66 segments (79%) at exercise. We conclude that this agent is promising for the diagnosis and evaluation of coronary artery disease. PMID- 8468798 TI - [Assessment of myocardial perfusion abnormality and hibernating myocardium by gated blood pool and exercise-stress thallium tomographies after successful coronary angioplasty]. AB - Cardiac function and myocardial perfusion were assessed by exercise-stress thallium SPECT and resting gated blood pool SPECT techniques before and after 47 successful coronary angioplasties. Thallium perfusion was analyzed visually and quantitatively in stress and resting studies. Left ventricular ejection fraction (LVEF) and peak filling rate (PFR) were calculated and regional wall motion was scored by amplitude and phase images in radionuclide planar and tomographic imagings. The thallium redistribution in delayed or resting SPECTs was more sensitive (87%) for detecting myocardial ischemia compared to symptoms (36%) and ECG changes (60%). An exercise capacity, LVEF, PFR, and the scores of perfusion and regional wall motion were improved significantly after coronary angioplasty. Stress thallium and gated blood pool SPECTs showed the improvements of myocardial perfusion in 159 (79%) of 201 segments and regional wall motion in 47 (51%) of 92 segments, respectively. These results suggest that the combined use of stress thallium SPECT, gated blood pool planar and SPECT techniques can contribute not only to the assessment of the efficacy of coronary angioplasty but also to detecting the mismatching of myocardial perfusion and contraction ("myocardial hibernation") in infarct-related myocardial lesions. PMID- 8468799 TI - [Regional cerebral blood flow in diabetic patients]. AB - N-isopropyl-p-123I-iodoamphetamine (IMP) was used to quantify the regional cerebral blood flow (r-CBF) in 11 diabetic patients (average age; 67.9 years) and 12 non-diabetic subjects (average age; 67.4 years), none of whom had CVD (Cerebrovascular disease) on CT studies. A reference sampling method by continuous arterial blood sampling was used to quantify r-CBF. There were no significant differences in physiological or laboratory data between diabetic and non-diabetic groups except for fasting plasma glucose and HbA1C levels. The average of r-CBF in each region of cerebrum and cerebellum was significantly lower in diabetic group than that in the control group (p < 0.01). These observations show that r-CBF of diabetic patients is reduced, even in the absence of findings of CVD on a CT study. PMID- 8468801 TI - [Role of 99mTc-labeled RBC SPECT in the diagnosis of hepatic hemangioma- comparison with US, CT and angiography]. AB - The roles of planar imaging and SPECT with 99mTc-labeled RBC, US, Dynamic CT and angiography in the diagnosis of hepatic hemangioma were evaluated. The study group consisted of 18 patients with a total of 40 hemangiomas and 13 patients with a total of 21 non-hemangiomas. Among these patients, 5 patients with a total of 8 hemangiomas and 10 patients with a total of 14 non-hemangiomas were diagnosed by operation and biopsy. In all 40 hemangiomas, sensitivity for planar imaging was 35%, SPECT 50%, US 53%, Dynamic CT 82% and angiography 81%, respectively. When the tumor size was greater than 2.2 cm by SPECT and 2.8 cm by planar imaging, their sensitivity for both methods was 100%. Specificity for planar imaging was 100%, SPECT 95%, US 81%, Dynamic CT 100% and angiography 83%, respectively. One patient with hepatocellular carcinoma diagnosed by angiography showed increased uptake on SPECT. Because of the highest accuracy for SPECT in hemangioma greater than 2.0 cm, SPECT should be considered to be the method of choice for noninvasive diagnosis of hemangioma. PMID- 8468800 TI - [Left ventricular hemodynamics in patients with sick sinus syndrome: analysis by 99mTc-RBC cardiac pool scintigraphy with forward and backward multiple gated method (FBMG)]. AB - The left ventricular (LV) systolic and diastolic functions in 31 patients with sick sinus syndrome (types I and II) were analyzed using LV time activity curves obtained by a 99mTc-RBC cardiac pool scintigraphy-forward and backward multiple gated study (FBMG) and compared with those in controls. On A-V sequential pacing (rate, 70 bpm; A-V delay, 150 msec), LV-peak ejection rate (PER) and peak filling rate (PFR) were significantly decreased compared to those in normal controls. As pacing rate was increased, PFR decreased significantly in patients in whom PER was decreased. The etiology of disturbed LV systolic and diastolic functions in patients with sick sinus syndrome remains unknown. No patient had significant organic coronary artery disease or other cardiac disorder. On the other hand, the frequency of vasospastic angina was higher in this group than in the controls. We suspect that sick sinus syndrome and vasospastic angina probably share a common pathophysiology. In patients with sick sinus syndrome, LV systolic and diastolic functions are impaired at rest and during A-V sequential pacing. PMID- 8468802 TI - [Phase I clinical study of 99mTc-MAG3]. AB - A phase I study was performed in three normal volunteers to evaluate the safety and biodistribution of 99mTc-MAG3 which was developed as a renal scintigraphic and renographic dynamic function agent. There was no significant adverse reaction, change in vital signs and clinical laboratory data by the injection of 99mTc-MAG3. Therefore it is assumed that the safety of the agent is high. Clearance of injected 99mTc-MAG3 from blood was rapid and the agent was excreted into urine. Immediately after administration of the agent, renal dynamic scintigraphy was performed and provided better quality of images and renograms. Peak time in the renogram was about 3 min post injection and residual count rate to the peak count at 20 min after injection was 19.3%. Cumulative urinary excretion during the first 30 min and 3 hr expressed in %Dose was 77.1 +/- 3.5% and 94.1 +/- 2.7%, respectively. Radiation dose estimates calculated with MIRD method, in the highest organ, bladder, is 5.78 mGy/200 MBq, which seems to be within permissible range for routine examination in nuclear medicine. It is concluded that 99mTc-MAG3 is a safe and promising radiopharmaceutical in diagnosis of renal dynamic function. PMID- 8468803 TI - [A study of crossed cerebellar diaschisis on 123I-IMP SPECT images and its redistribution phenomenon]. AB - Crossed cerebellar diaschisis (CCD) is interpreted as a functional deactivation, presumably caused by a loss of excitatory or inhibitory afferent inputs on the corticopontocerebellar pathway and others. A redistribution phenomenon (RD) is usually observed in the contralateral cerebellum with CCD on delayed images of 123I-IMP SPECT. This phenomenon was analyzed in a view point of rCBF measurement in 24 patients with brain tumor, infarction and so forth. Regional CBF was measured by the microsphere method with 123I-IMP and a delayed-to-early counts ratio (D/E ratio) was used. As a result, there was no relation between rCBF and the D/E ratio in the cerebellum, which means that RD is occurred by other factors except for rCBF in the cerebellum. Regional CBF and the D/E ratio in the contralateral and ipsilateral cerebellum was 46.3 ml/100 g/min, 1.01 and 57.0 ml/100 g/min, 0.86, respectively. These results mean that the high activity of IMP gradually decreased in the ipsilateral cerebellum, while, the low activity in the contralateral cerebellum was almost stable, and the difference of both activity reduced after 5 hours and RD was observed on the delayed image. The data indicate that retention mechanism of IMP and vascular permeability are not affected in the cerebellum with CCD. PMID- 8468804 TI - [A case of Down's syndrome with progressive dementia of Alzheimer type]. AB - A rare case of Down's syndrome complicated with progressive dementia of Alzheimer type in a 41-year-old man was reported. On 123I-IMP SPECT, the patient revealed symmetrical bilateral temporo-parietal hypoperfusion. This finding seemed to support the developing dementia of Alzheimer type on the basis of clinical manifestations. 123I-IMP SPECT seemed to be useful for early diagnosis of Alzheimer-like change in a natural course of Down's syndrome. PMID- 8468805 TI - [Lymphoscintigraphy with 99mTc-DTPA-HSA in the diagnosis of protein-losing gastroenteropathy]. AB - We evaluated the diagnostic capability of technetium-99m-diethylene triamine pentaacetic acid-human serum albumin (99mTc-DTPA-HSA) lymphoscintigrapy in a patient with protein-losing gastroenteropathy. 99mTc-DTPA-HSA (total 740 MBq) was injected subcutaneously into the digital webs of the both feet. With a gamma camera, whole-body and abdominal lymphoscintigrams were obtained after the injection of the radioisotope: early images and delayed images taken 5-15 min and 50-60 min, respectively, after the injection. A few days later, the dynamic lymphoscintigraphy was also performed. Lymph fluid leakage into the small bowel and the sites of the leakage were detected. It was concluded that lymphoscintigraphy with 99mTc-DTPA-HSA was a useful diagnostic tool in patients with protein-losing gastroenteropathy. PMID- 8468806 TI - [Crosstalks onto photopeak windows of 99mTc and other radionuclide (201Tl, 123I or 111In) in simultaneous acquisitions using a scinticamera--a fundamental study through phantom experiments]. AB - In simultaneous acquisitions of both 99mTc and other radionuclide, there are crosstalks onto those photopeak windows. Therefore, to quantify the organ uptake in scintigraphic imaging, it is important to correct the crosstalk counts. The purpose of this study is to estimate the crosstalk fractions onto each photopeak window from other radionuclide. Those crosstalk fractions were determined from pulse height spectra, which were measured by inputting signals from a scinticamera into a multi-channel (2048 ch) pulse height analyzer. Four types of collimators, which are HR (high resolution), AP (all purpose) for low energy, ME (medium energy) and HE (high energy), as well as cuboid phantoms (10 x 10 x 10 cm3) were used in this experiment. The crosstalk fractions have a tendency to show small increases at the window width of 10 to 20%, excepting at 30%, a small change for the source thickness from 1 to 7 cm, and the least with the ME collimator. The crosstalk fractions using the ME-collimator were obtained as follows, when the source thickness and the window width were 5 cm and 15%, respectively. 99mTc and 201Tl: 9.4% onto 201Tl window and 7.3% onto 99mTc window, 99mTc and 123I: 36.1% onto 99mTc window and 14.8% onto 123I window, 99mTc and 111In: 32.6% onto 99mTc window and 6.1% onto 111In window. PMID- 8468807 TI - [Clinical application of 99mTc-DTPA-galactosyl serum albumin in hepatobiliary disease]. AB - A clinical study with 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA) was performed in 10 patients with hepatobiliary disease. In this study, scintigraphic data and images with 99mTc-GSA were compared with several serological liver function tests, the hepatic blood perfusion index and image quality using 99mTc DTPA-human serum albumin (99mTc-HSA). Dynamic and serial hepatic images were obtained over a 20 min period after 99mTc-GSA injection, and time activity curves from the heart and liver were generated. The blood clearance index (HH15), and the hepatic uptake index (LHL15) were calculated from each curve of the heart and liver, respectively. In addition, using two compartment fitting, the blood clearance (KH1, KH2) index was calculated, and using exponential fitting, the hepatic uptake index (KL) was calculated. The mean HH15 in LC group and non-LC group was 0.81 +/- 0.05, 0.64 +/- 0.10, respectively. The mean LHL15 in LC group and non-LC group was 0.79 +/- 0.04, 0.91 +/- 0.06, respectively. There were significant differences between non-LC group and LC group in HH15, and LHL15, KH1 and KL. There were also significant correlations of KH1 with HH15, and KL with LHL15. Parameters of 99mTc-GSA showed significant correlations with various liver functions. 99mTc-GSA scintigraphy showed clearer liver images in hepatobiliary diseases than 99mTc-HSA. These results suggest that 99mTc-GSA scintigraphy is useful in estimating preserved liver function and hepatic morphology. PMID- 8468808 TI - [The indications for the use of gallium-67 scintigraphy]. AB - 67Ga citrate scanning has been widely used for imaging a variety of neoplasms and inflammatory lesions. In this review, indications and limitations of 67Ga scanning were briefly discussed, and four diseases, that is, sarcoidosis, malignant melanoma, malignant lymphoma and opportunistic infection in patients with AIDS, were mentioned as the indications for 67Ga scanning in the clinical evaluation. Especially 67Ga scanning is helpful in the early detection and differential diagnosis of opportunistic infections in AIDS patients. I am convinced that 67Ga scanning will continue to be used for the future in view of its rich experience, simplicity and safety, although the exact role of 67Ga scanning should be defined. PMID- 8468809 TI - [Serum and urinary neopterin levels in sarcoidosis]. AB - Serum and urinary neopterin levels were determined by high pressure liquid chromatography in 26 patients with pulmonary sarcoidosis and 12 healthy controls. Neopterin levels were significantly higher in sarcoidosis patients than in the controls. Neopterin levels differed from serum angiotensin converting enzyme (ACE) activities and were significantly higher in radiologic stage 1 and 2 than in radiologic stage 0 in patients not receiving prednisolone. No significant correlation was found between neopterin level and serum ACE activity. On the other hand, a significant correlation was found between neopterin level and serum adenosine deaminase activity. We believe that serum and urinary neopterin levels may be a more clinically valuable method of assessing pulmonary sarcoidosis than serum ACE activity. PMID- 8468810 TI - [A case of pulmonary actinomycosis that was difficult to distinguish from pulmonary carcinoma]. AB - A 45-year-old male was admitted with chief complaint of hemoptysis. Prior to admission, a tumor in the S3 segment of the right lung had been detected by chest radiography. Despite a detailed examination after admission, no definite diagnosis was made, and right upper lobectomy was performed. Histopathological examination of the surgically resected tissue led to the diagnosis of pulmonary actinomycosis. In Japan, 52 cases of this condition were reported between 1964 and 1991. This paper discusses the epidemiology, diagnosis and diagnostic imaging of the condition, with reference to the literature. PMID- 8468811 TI - [A case of idiopathic chylothorax]. AB - A 29-year-old female was admitted to our hospital because of right pleural effusion. Chyle was obtained by thoracocentesis. She received conservative therapy, however, the pleural effusion did not decrease. Thoracic duct ligation was performed, and improvement of the chylothorax was observed. Because there was no underlying disease to cause chylothorax, the diagnosis of idiopathic chylothorax was made. Idiopathic chylothorax is a rare disease and only 24 cases have been reported in Japan. PMID- 8468812 TI - [A case of chylothorax resulting from malignant lymphoma--pathogenesis of chylothorax: a new concept]. AB - We report a case of chylothorax in a 51-year-old male with non-Hodgkin's lymphoma. Combination chemotherapy reduced the size of mediastinal lymph nodes dramatically, but retroperitoneal lymph nodes remained almost the same, and chylothorax subsequently developed. Lymphangiogram showed reticular spread of contrast material from the thoracic duct downwards but not above the diaphragm. These findings suggest that an obstruction of the infra-diaphragmatic but not the supra-diaphragmatic thoracic duct caused development of collateral lymphatic channels penetrating the diaphragm into the thoracic cavity, with subsequent formation of chylothorax. PMID- 8468813 TI - [A case of intrapulmonary lymph node with silicotic nodules in a patient with idiopathic interstitial pneumonia]. AB - A 61-year-old man was admitted to our hospital on October 8, 1991 because of abnormal shadows on chest X-ray at annual checkup at his company. Chest X-ray and CT on admission showed diffuse reticular shadows in bilateral lower lung fields and a nodular opacity approximately 10 mm in diameter in the right lower lung. Since transbronchial lung biopsy was not diagnostic, an open lung biopsy was performed on October 28, 1991. The lung specimens showed diffuse pulmonary fibrosis compatible with usual interstitial pneumonia and an intrapulmonary lymph node containing silicotic nodules. Only 29 cases (including the present case) of intrapulmonary lymph nodes have been reported. Although the causes of intrapulmonary lymph nodes are not clear, smoking is considered to play an important role in the development of pulmonary lymphoid tissue. In our case, the intrapulmonary lymph node contained silicotic nodules. Only several case have been reported to have silicotic nodules in the lymph nodes. As suggested by Kradin, they may be induced by relatively low levels of exposure to dust. Our case also had pulmonary fibrosis (IIP), and is the first reported case of intrapulmonary lymph node associated with IIP. Although it is difficult to determine these two diseases occurred coincidently or not, it is possible that a low level of dust exposure may have contributed to both silicotic nodules in the lymph node and IIP. PMID- 8468815 TI - [A case of plasma cell granuloma which resolved after steroid treatment]. AB - A 65-year-old man with a history of a common cold two months earlier was referred to our division for further evaluation of an abnormality on chest X-ray film. Transbronchial lung biopsy findings revealed an inflammatory pseudotumor, a plasma cell granuloma (PCG). The pulmonary nodule disappeared completely six weeks after steroid therapy. To our knowledge, all PCG cases to date have been surgically resected. Therefore, this case of PCG diagnosed by transbronchial lung biopsy and successfully treated nonsurgically with steroid therapy is worthy of note. PMID- 8468814 TI - [Bronchial hyperresponsiveness to histamine induced by intravenous administration of 9 alpha,11 beta-prostaglandin F2 (9 alpha,11 beta-PGF2) in guinea pigs]. AB - The effects of intravenous administration of 9 alpha,11 beta-PGF2, a stable metabolite of prostaglandin D2 (PGD2), on bronchial smooth muscle in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance using a formula to exclude the effects of differences in airway wall thickness. With this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness to histamine. Administration of 9 alpha,11 beta-PGF2 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly enhanced by the administration of 9 alpha,11 beta-PGF2a. TXA2 antagonists, ONO-NT 128 and ONO-8809, inhibited the effect of 9 alpha,11 beta-PGF2 administration. These results suggest that 9 alpha,11 beta-PGF2 act as important mediators affecting bronchial hyperresponsiveness, and TXA2 may play a role in 9 alpha,11 beta-PGF2-induced airway wall edema and bronchial hyperresponsiveness to histamine. PMID- 8468816 TI - [Experimental epithelioid cell granuloma formation in Lewis rats induced by injection of cell wall fragments derived from alpha-streptococcus--etiologic relationship between bacterial cell wall and sarcoid granuloma]. AB - We observed the presence of epithelioid granulomas in follicles near lacunae in the tonsils from patients with active sarcoidosis. Bacteria isolated in these tissues were mostly alpha-streptococci. The present study was undertaken to determine whether alpha-streptococcus can induce granuloma formation. Streptococcal cell wall (SCW) fragments were injected into the foot pads of female Lewis rats. Epithelioid granulomas were abundantly formed in popliteal lymph nodes when SCW aqueous suspension was injected four times. SCW antigens were detected in macrophages in the granuloma but not in epithelioid cells, by immunoperoxidase method. These findings suggest that macrophages transform into epithelioid cells after phagocytosis and digestion of SCW, and that components of bacterial cell wall such as SCW may induce the granuloma formation in sarcoidosis. PMID- 8468817 TI - [Bulky mediastinal malignant lymphoma]. AB - The efficacy of treatment of 19 patients with malignant lymphoma presenting with mediastinal tumor was evaluated. They included 7 patients with Hodgkin's disease and 12 with non-Hodgkin's lymphoma (NHL). Numbers of patients with stage I, II, III and IV disease according to Ann-Arbor's classification were 6, 4, 3 and 6, respectively. Stage I patients were treated with CHOP therapy after radiotherapy (RT). Stage II and III patients were treated with RT after COP-BLAM chemotherapy. Stage IV patients were treated with COP-BLAM III regimen. Complete remission was achieved in 16 of 19 patients (84.2%), and partial remission in 2 (10.5%). All patients with Hodgkin's disease and 9 (75%) with NHL attained complete remission. All patients in stage I to III and 3 (50%) in stage IV achieved complete remission. Overall median survival was 66 months. The incidence of bone marrow involvement and bulky mass was significantly different between stage I.II and stage III.IV patients (p < 0.05). These results indicate that combination treatment with RT and chemotherapy with regimens including adriamycin was effective in patients with malignant lymphoma presenting with mediastinal tumor, especially in those without bone marrow infiltration and bulky mass. PMID- 8468818 TI - [A new technique for evaluating the respiratory tract--digital subtraction bronchography (DSBG)]. AB - Bronchography is essential for evaluation of morphological changes in the bronchial tree. However, conventional bronchography using Propyliodone (Dionosil) is extremely invasive, especially to those with pulmonary infections. In the present study, we developed a new less invasive method of bronchography with the aid of digital subtraction technique (DSBG), and evaluated its clinical benefits. Bronchography was performed by injecting contrast medium (Iopamidol: Iopamiron 300) via the lumen of the bronchoscope (Olympus Type 20), and image processing of the respiratory tract was performed using digital subtraction technique. From 1991 to 1992, DSBG was performed in 15 cases (8 bronchiectasis, 1 diffuse panbronchiolitis, 1 lung cancer, 1 pulmonary emphysema, and 4 others). DSBG clearly demonstrated the morphological changes of large and segmental bronchial lesions in cases of bronchiectasis and lung cancer, as well as conventional bronchography using Dionosil. In addition, it was possible to image the morphological changes of bronchiolar lesions in diffuse panbronchiolitis and pulmonary emphysema to the same detail as obtained using classical selective alveolo-bronchography (SAB). Since DSBG can provide enhanced images the bronchial tree without being affected by cardiac and respiratory movements, we could obtain detailed information on bronchial and/or bronchiolar lesions. With respect to side effects, Iopamiron was quickly drained and/or absorbed within 2 hours after injection. Pulmonary infection and bronchial bleeding, which are well known primary complications of classical bronchography using Dionosil, were not observed. We conclude that 1) DSBG is useful new technique for examining morphological changes of the respiratory tract, and 2) DSBG is less invasive than conventional bronchography. PMID- 8468819 TI - [Airway hyperreactivity test by measurement of specific airway conductance during quiet breathing]. AB - In asthmatic patients, the threshold for specific airway conductance during quiet breathing (sGawqt) in the airway hypersensitivity test was determined using our newly developed pressure corrected flow type body plethysmograph and compared with that measured by means of respiratory resistance (Grs) Astograph in relation to the following parameters: 1) Dmin, an index of airway sensitivity (accumulated methacholine concentration at the time of onset of linear decrease in the dose response curve), 2) SsGawqt and SGrs, indicators of airway sensitivity (slope when the value begins to decrease) and 3) PD35 (accumulated methacholine concentration when the valve has decreased to 35% of the initial value). Although no significantly difference was observed in SsGawqt and SGrs, significantly lower values of Dmin and PD35, indexes of airway sensitivity, were obtained with sGawqt method as compared to Astograph. These findings may indicate that the airway hypersensitivity test using our body plethysmography technique can be performed using a smaller amount of inhaled methacholine with less patient burden as compared to Astograph. PMID- 8468820 TI - [Effects of various doses of endotoxin on physiological and hematological parameters in conscious guinea pigs]. AB - We investigated the effects of various doses (0.2 to 2000 micrograms/kg) of endotoxin on physiological and hematological parameters in our guinea pig model. Bronchoalveolar lavage (BAL) and lung tissue sampling were performed 6 hours after endotoxin injection. Lung damage was assessed by measuring wet to dry lung weight ratio (W/D), lung tissue to plasma accumulation of 125I-albumin (AL: albumin leakage) and BAL fluid to plasma accumulation of 125I-albumin (BALL: bronchoalveolar lavage leakage). Changes in peripheral cell counts were estimated at times 0, 1, 2, 4 and 6 hours after endotoxin injection. Pulmonary cell accumulation was determined by counting the number of cells in BAL fluid and tissue samples fixed for light microscopic examination. Increased W/D and AL were observed only in the high dose endotoxin treatment groups (200 and 2000 micrograms/kg), while BALL increased even in the low dose endotoxin treatment groups (2 micrograms/kg). Decreases in peripheral neutrophil counts at one hour were observed in all endotoxin treated groups. Increase in BAL fluid neutrophils was seen in the 20, 200, and 2000 micrograms/kg groups, while neutrophil accumulation assessed by light microscope was observed in all endotoxin treated groups. We conclude that different amounts of endotoxin are required to affect different parameters of lung injury. PMID- 8468821 TI - [Clinical features and prognosis of Churg-Strauss syndrome]. AB - We studied the clinical features and prognosis of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 1 man and 10 women with a mean age of 56.3 years. All subjects had a history of bronchial asthma prior to the onset of CSS. It was noted that the age of onset of bronchial asthma was high, and most of the patients had suffered from frequent and severe asthmatic attacks during the periods preceding the vasculitis. Skin tests and IgE RAST revealed that less than half of the subjects were atopic. Therefore it is considered that asthmatics with late onset and severe symptoms have a high risk for CSS, and poor control of asthmatic symptoms may contribute to the onset of the vasculitis. Eleven of 12 cases including 1 patient with a relapse were treated with PSL alone (9 cases) or PSL plus cyclophosphamide (2 cases). Three patients died of heart failure or central nerve involvement. Vasculitis was ameliorated in the other cases (75%). Seven patients received maintenance therapy with low-dose of PSL (5 cases) or cyclophosphamide (2 case). None suffered from relapse of vasculitis during maintenance therapy. Discontinuation of therapy in five cases resulted in a relapse in only one case 62 months after the cessation of low-dose PSL. Although maintenance therapy appears to be useful in some CSS patients, the significance and indications for maintenance therapy should be further clarified. PMID- 8468822 TI - [A case of lung adenocarcinoma with high CT number, high calcium concentration but no calcification]. AB - A 36-year-old woman with lung adenocarcinoma is reported. Chest X-ray film showed a high CT number, but no calcified lesion was detected. Histologic examination demonstrated no bone formation, calcification, or psammoma bodies. Calcium staining with Kossa method was negative. An elementary analysis with penetrating type electron microscopy and energy dispersion type analyzer showed high calcium concentration in the tumor. It was thought that the tumor showed a high CT number because of masked soluble calcium. PMID- 8468823 TI - [A case of primary pulmonary lymphoma associated with Sjogren syndrome and IgM monoclonal gammopathy confirmed by DNA rearrangement]. AB - A 70-year-old man was admitted for evaluation of an abnormal shadow on his chest X-ray film, consisting of a mass containing an air bronchogram. He was also found to have a monoclonal gammopathy (IgM kappa type) and Sjogren syndrome. Open lung biopsy was performed with the suspicion of primary pulmonary lymphoma or pseudolymphoma. Southern blot analysis of the tissue revealed clonal rearrangements of immunoglobulin gene, supporting the diagnosis of B-cell lymphoma. Using conventional immunoperoxidase staining (PAP) method, the monoclonality in the tissue specimen is sometimes quite difficult to prove. Southern blot analysis, however, gives more accurate and reliable results. The analysis of immunoglobulin gene rearrangements is quite useful in determining the presence or absence of monoclonality in a specimen in cases of suspected lymphoproliferative disease such as primary pulmonary lymphoma and pseudolymphoma. We strongly recommend the use of Southern blot analysis in making the diagnosis of lymphoproliferative disease. PMID- 8468824 TI - [Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test]. AB - We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test. PMID- 8468825 TI - [A case of chest wall abscess due to Salmonella newport]. AB - A 18-year-old female with a history of precordial pain was admitted. There was a mass (3.5 x 2.5 cm) in the right inframammary region which was suspected to be chest wall tumor on the basis of CT scan and Ga scintigraphy findings. Exploratory surgery, consisting of total resection of the tumor without removing the ribs, was performed and revealed an abscess. Culture of pus from the abscess grew Salmonella newport (0 antigen 8, H antigen eh; 1.2). Focal infection with Salmonellosis is discussed. Surgical treatment is necessary in addition to chemotherapy. PMID- 8468826 TI - [A case of multiple broncholithiasis caused by mucus retention]. AB - The patient was a 57-year-old male with long-standing bronchiectasis who developed severe respiratory failure and died in 1991. Autopsy revealed multiple broncholithiasis in both lungs, but no calcified lymph nodes in the hilar region. Since histological examination of the broncholiths showed only stratified structures but no tissue structure, most likely cause was considered to be calcification of mucus in the bronchi. Analysis of the stone components revealed 78% calcium and 22% protein. This patient represents a case of multiple broncholithiasis caused by mucus retention, which is thought to be very rare. PMID- 8468827 TI - [A case of pulmonary arteriovenous fistulas (PAVF) treated with detachable balloon embolotherapy]. AB - A case of pulmonary arteriovenous fistulas (PAVF) treated with detachable balloon embolotherapy is reported. A 31-year-old man was admitted to hospital because of polycythemia and hypoxemia. He had a history of dyspnea on exertion and transient cerebral ischemic attacks (TIA). Chest roentgenogram revealed a peripheral lobulated lesion in the right upper lung field and a coin lesion in the left lung field connected by dilated blood vessels to each hilus. Pulmonary angiography and right heart catheterization was performed. Four PAVFs were observed in bilateral lung field, and the intrapulmonary shunt ratio was 25.8%. Because the patient was symptomatic, we embolized each PAVF with a detachable balloon without complications. After embolotherapy, there was improvement in his symptoms. hypoxemia and shunt ratio. Recent reviews have highlighted the need to consider embolotherapy for bilateral multiple PAVF. We conclude that embolotherapy with detachable balloon is a very useful procedure for treatment of bilateral multiple PAVF. PMID- 8468828 TI - [A case of neurinoma combined with testicular feminization syndrome]. AB - A 23-year-old female was admitted to our hospital because of a mediastinal tumor. She complained of primary amenorrhea, and abdominal echosonography was therefore performed, revealing the absence of a uterus. Chromosome analysis revealed a 46 XY genotype, indicating the patient to be a male, not a female. Left renal venography demonstrated residual blood vessels originating in the Mullerian ducts. Thoracotomy and laparotomy were performed, and the mediastinal tumor and bilateral testes were resected. Postoperative pathology revealed that the mediastinal tumor was a neurinoma. There was no spermatogenesis, but hyperplasia of Sertoli cells in the testes was seen. Neither the neurinoma nor the testes were malignant. Bioassay of the testes showed no androgen receptors, leading to the diagnosis of testicular feminization syndrome with the complete form of androgen insensitivity. There have been many reports of an association between testicular feminization syndrome and malignant tumors of the testes, but few reports of an association between testicular feminization syndrome and benign tumors such as neurinoma. Accordingly, the present case was considered to be unusual and worth reporting. PMID- 8468829 TI - [A case of pulmonary embolism probably induced by long term use of oral contraceptive]. AB - We present a 53-year-old female with pulmonary embolism (PE), who had been taking oral contraceptive for 13 years. She was admitted to our hospital with upper abdominal pain and was found to be in shock. The diagnosis of PE was made from chest X-ray examination, electrocardiogram and pulmonary angiography. Pulmonary hypertension was observed on right heart catheterization, and an anticoagulant was administered. Multiple defects of the right pulmonary artery were detected on lung perfusion scan, and there were no significant findings on leg phlebogram. Home oxygen therapy was effective for the treatment of pulmonary hypertension and chronic hypoxemia which still persisted after her recovery from the acute stage. We are concerned that wide spread use of oral contraceptives will increase the incidence of PE in the near future in this country. We conclude that contraceptive users should be warned of their higher risk of PE, and that they should visit a clinic for examination. PMID- 8468830 TI - [Comparison of typical and atypical bronchoplasty for bronchogenic carcinoma]. AB - One-hundred and twenty-eight patients who underwent bronchoplasty for bronchogenic carcinoma from 1969 to 1990 were retrospectively analyzed. Ninety six patients had upper sleeve lobectomy or upper lobectomy with wedge bronchoplasty (typical procedure) and 32 underwent bronchoplasty with lobectomy other than upper lobes (atypical bronchoplasty). The two groups were statistically similar in preoperative characteristics including sex, age, cell types and stages. In typical group, right upper sleeve lobectomy was performed in 48 patients, left upper sleeve lobectomy in 27, right upper lobectomy with wedge bronchoplasty in 11, left upper lobectomy with wedge bronchoplasty in 7 and sleeve bronchoplasty alone in 2. In atypical group, right middle and lower lobectomy with sleeve bronchoplasty in 10 patients, left lower sleeve lobectomy in 5, right lower lobectomy with wedge bronchoplasty in 4 and others in 13. Postoperative mortality was 5.2% in the typical group and 9.4% in the atypical group. Postoperative respiratory complications occurred in 16 patients (50%) in the patients with the atypical group and in 33 (34.7%) in those with typical group. Three years and 5 years survival rates in the typical group were 46 and 40% and those in the atypical group, 27 and 18%. However, there was no statistical difference in survival between the two groups. In conclusion, atypical bronchoplasty is useful for preserving the lung parenchyma, but, careful perioperative management and surgical technique of bronchoplasty are mandatory. PMID- 8468831 TI - [A right internal thoracic artery graft to the left anterior descending artery]. AB - From 1987 to 1991, 48 patients received a right internal thoracic artery (RITA) to the left anterior descending artery (LAD). No operative death occurred, but two patients (4.2%) died during hospitalization due to graft versus host disease, and congestive heart failure. Graft patency of the RITA was 100%. After a 17.2 month mean follow-up, the 4 year actuarial survival rate (including all causes of death) was 85.3%, and the 4 year cumulative cardiac event free rate (including all cardiac deaths, myocardial infarction, reoperation, and PTCA) was 87.6%. The length of the RITA graft to the LAD, 15.6 +/- 1.1 cm, was significantly longer than that of the left internal thoracic artery (LITA) to the LAD, 12.9 +/- 1.1 cm. However, the flow of the RITA-LAD graft, 42.3 +/- 21.1 ml/min, was same as the flow of the LITA to the LAD, 42.1 +/- 19.6 ml/min. These findings justify wider use of the RITA to the LAD as a second arterial graft. PMID- 8468832 TI - [Measurement of cardiac output by Doppler echocardiography: clinical validation in pediatric patients after open heart surgery]. AB - We compared the cardiac output obtained by pulsed Doppler echocardiography (COPW) with simultaneous thermodilution measurements (COTD) in 13 children for 33 times after open heart surgery. Good correlation (r = 0.84, slope = 1.15) of cardiac output was obtained when direct measurements of aortic diameter during operation were used in the calculations. Cardiac output was overestimated (r = 0.89, slope = 1.42) when 2 DE measurements of aortic diameter were used. Nineteen measurements of 8 VSD patients revealed good correlation (r = 0.89, slope 0.85) using direct measurement of aortic diameter, whereas 14 measurements of TOF patients showed somewhat overestimation of cardiac output (r = 0.90, slope = 1.31). In serial determinations, percent change change in COPW well correlated with COTD (r = 0.75, slope = 1.08). We conclude that accurate cardiac output can be obtained by pulsed Doppler echocardiography after pediatric cardiac surgery by measuring aortic diameter directly in operation room. Accuracy in percent change in cardiac output proved that COPW is useful especially in hemodynamically unstable patients after pediatric cardiac surgery. PMID- 8468833 TI - [Thoracoscopic treatment of bronchogenic cyst]. AB - A central bronchogenic cyst was excised thoracoscopically from a 44-year-old woman in whom a tumor had been pointed out in the left upper posterior mediastinum at a screening examination. Since the tumor was diagnosed to be benign, only conservative follow-up was undertaken, but the patient consulted our department desiring active therapy. On the basis of the chest CT and MRI findings a bronchogenic cyst was diagnosed. Under general anesthesia and mechanical ventilation of one lung, the thoracoscope was inserted into the thoracic cavity revealing in the left upper posterior mediastinum a cyst which was excised thoracoscopically. While coagulation was performed gingerly with an electric scalpel, the tumor was detached sharply and bluntly with a pair of scissors. The postoperative course was uneventful with little wound pain or scar formation. Hitherto bronchogenic cysts have been treated by resection after thoracotomy. Although this is an easy procedure, a relatively large operative scar is left and considerable wound pain may develop. In contrast, thoracoscopic treatment is characterized by minimal surgical invasiveness, little postoperative wound pain, and small scars. These advantages suggest that this technique may be indicated for benign mediastinal tumors, particularly cysts. PMID- 8468834 TI - [Thoracoscopic partial resection of the lung for peripheral lung tumor]. AB - We report a thoracoscopic partial resection of the lung for the peripheral lung tumor in a 66-year-old woman. Her chest roentgenogram and computed tomographic scan showed a single tumor 1.9 cm in diameter within the periphery of the right lower lobe. A solitary metastatic lung tumor of colon cancer, which was resected one year ago, was suspected. Partial resection of the lung involving this tumor was performed using the MULTIFIRE ENDO GIA 30 disposable surgical stapler under thoracoscopy. There was neither air leak nor bleeding at the resection line. Pathological examination of the tumor revealed benign localized pleural mesothelioma. Her postoperative course was uneventful and she was discharged from the hospital on the eighth postoperative day. Thoracoscopic pulmonary resection using EndoGIA is a safe technique for a peripheral lung tumor. PMID- 8468835 TI - [Bullectomy utilizing EndoGIA under thoracoscopic guidance]. AB - We report 5 cases of pneumothorax successfully treated with an endoscopic GIA stapling device (EndoGIA) under thoracoscopic guidance. There were no complications such as air leak or bleeding, and patients were discharged 2 to 7 days after operation. Surgical procedure utilizing EndoGIA has been proved to have advantages such as less pain, early return to normal activity and more cosmetic incision. PMID- 8468836 TI - [The partial resection of lung with MULTIFIRE ENDO GIA 30 under the thoracoscopy]. AB - MULTIFIRE ENDO GIA 30 was a newly auto suture developed by US surgical c.o., A 27 year-old man was admitted for right spontaneous pneumothorax in our hospital. We performed the partial resection of lung with this new auto suture under the thoracoscopy. Condition of patient after operation was very good, and he could discharge in short hospitalization. We concluded that this new auto suture was entirely reversible and safety. PMID- 8468837 TI - [Palliative management of left atrioventricular valve atresia with normal aortic valve]. AB - We present three cases of the left atrioventricular valve atresia (LAVVA) with normal aortic valve. All cases showed [S,D,D] and had concordant AV connection. First case had two functional ventricles with multiple VSD and ventriculo arterial connection was normal. Interatrial communication was maintained through ASD and the infant underwent pulmonary arterial banding (PAB). Four years later, the patient underwent Blalock-Hanlon (B-H) procedure for an inadequate ASD. Second case showed the univentricular heart of right ventricle with double outlet. In this case, PFO was restrictive and the infant underwent B-H procedure. Ten days after initial palliation, patient underwent PAB. Third case showed the univentricular heart of left ventricle and transposed great arteries. This patient had also the coarctation of the aorta. B-H procedure, PAB and subclavian flap aortoplasty were performed simultaneously by bilateral thoracotomy. All patients have done well, with normal growth and development at the time of their last outpatient evaluation at 10 year, 9 months and 9 months after surgery respectively. PMID- 8468838 TI - [Clinical use of an expanded polytetrafluoroethylene sheets (GORE-TEX SHEETS) as a pericardial substitute after aorto coronary bypass grafting]. AB - Reoperation after cardiovascular surgical procedures are often accompanied by the possibility of injuring the heart the great vessels, and extracardiac grafts during resternotomy. To reduce the risk associated with resternotomy and to facilitate dissection of intrapericardial adhesion, we have used GORE-TEX SHEET as pericardial substitute since January, 1989. In case GORE-TEX SHEET are implanted in the mediastinum, prolongation of the foreign body reaction, mediastinitis, increasing postoperative hemorrhage should be in mind. In this study, the biocompatibility of GORE-TEX SHEET was examined clinically. The following postoperative indices such as duration of fever, change of the WBC counts, WBC fraction, CRP, mediastinal hemorrhage are evaluated. These results showed no statistical significance between GORE-TEX SHEET group and autologous pericardial group by the randomized study. We recommend use of GORE-TEX SHEET as a pericardial substitute in cases of major cardiovascular operation using median sternotomy. PMID- 8468839 TI - [Blood purification after aorto-coronary bypass grafting for dialysis patients]. AB - Four dialysis patients received aorto-coronary bypass grafting (CABG) at Fukuyama cardiovascular hospital from April 1989 to March 1992. We employed continuous ambulatory peritoneal dialysis (CAPD) in two cases, hemodialysis with extracorporeal ultrafiltration method (ECUM + HD) in one case and hemodiafiltration with continuous veno-venous hemofiltration (CVVHF + HDF) in one case for perioperative management. In each cases, intermittent HD was undergone during 4 days before operation. Intraoperatively, HD was used together with extracorporeal circulation. Blood pressure in the postoperative course changed more frequently in CAPD cases than ECUM + HD or CVVHF + HDF case. Especially, CVVHF + HDF stabilized the movement of circulation and kept balance of serum BUN, Cr after the operation (BUN; 27.2 +/- 6.3, Cr; 5.0 +/- 0.6). We concluded that CVVHF + HDF would be the most favorable method to maintain the fluid balance stably for the uremic patients after CABG. PMID- 8468840 TI - [An operative case of aortic valve regurgitation due to blunt trauma to the chest]. AB - While a 70-year-old man was riding a motorcycle, he was hit by car on his chest on October 19, 1990. Medical check-up at the emergency room of another hospital was negative. However, he fell in to dyspnea on the night of next day which progressed to develop signs of orthopnea. He revisited the hospital where he was found to have aortic regurgitation and subsequent congestive heart failure after medical examination including echocardiography and was referred to our hospital 7 days after the accident. He was operated upon the following day. On opening the pericardium, about 100 ml of reddish black fluid was accumulated. The appearance of the heart was normal except for black discoloration of the epicardial fat pad at the base of the aorta. Opening the ascending aorta transversely, the right coronary cusp was found to be perforated. The aortic valve was considered preferable to replace than to repair. The aortic valve was replaced with a St. Jude Medical valve. His recovery was uneventful and he has been well thereafter. PMID- 8468841 TI - [Acute cardiac tamponade in nonpenetrating injury of proximal aorta: report of a case]. AB - A 21-year-old male admitted to the emergency room with multiple traumatic injuries and shock. Although a chest X-ray showed normal in size of cardiac shadow, echocardiography confirmed cardiac tamponade. A median sternotomy was performed and the pericardial space was evacuated of 600 ml of blood and blood clots. Minor bleeding was identified in the proximal aorta, and complete hemostasis was achieved with manual compression and fibrin glue sealing. One month follow-up showed no pseudoaneurysm formation. PMID- 8468842 TI - [Primary chylopericardium with skeletal lymphoangiomatosis: a case report]. AB - A 5-year-old girl admitted to our hospital complaining cardiomegaly due to pericardial fluid and punched-out area in the humerus. Analysis of pericardial fluid confirmed primary chylopericardium and the findings in the humerus suggested skeletal lymphoangiomatosis. Despite medical treatments, pericardial fluid didn't decrease. Therefore, she underwent ligation and resection of thoracic duct. She recovered uneventfully without reaccumulation of the pericardial effusion. In addition, skeletal survey resulted in lymangiomatosis. PMID- 8468843 TI - [Anomalous origin of the left coronary artery from the pulmonary artery: a case report in an adult]. AB - A 37-year-old female with anomalous origin of the left coronary artery from the pulmonary artery was surgically treated by creation of intrapulmonary aorto coronary tunnel. Postoperative cardiac catheterization showed a minimal pulmonary stenosis at the baffle. But the remarkable preoperative ST-depression in a treadmill exercise test disappeared completely after operation and the normograde blood flow of the left coronary artery was detected from the ascending aorta. PMID- 8468844 TI - [Direct implantation of the left coronary artery to the ascending aorta in Bland White-Garland syndrome]. AB - A seventeen-year-old male with Bland-White-Garland syndrome underwent direct implantation of the left coronary artery to the ascending aorta. Under cardiopulmonary bypass, the main pulmonary artery was completely transected and the left coronary artery (LCA) was excised with a cuff of the pulmonary artery wall. Then the proximal end of LCA was directly anastomosed to the ascending aorta. The postoperative course was excellent. It appears that this surgical procedure might be the most ideal repair both anatomically and hemodynamically to reconstruct the left coronary artery in Bland-White-Garland syndrome. PMID- 8468845 TI - [A case report of pulmonary valve blood cyst]. AB - A six-year-old boy with pulmonary stenosis was hospitalized in order to examine the cause of pulmonary stenosis. The right-ventriculography showed a large shadow defect in the right ventricular outflow tract. But the echocardiography showed the cystic tumor, which was covered with thin wall and had echo-free space in it, in the right ventricular outflow tract. We made a diagnosis of pulmonary blood cyst. After cardiopulmonary bypass was established, the main pulmonary artery was incised longitudinally. There were two blood cysts at the left pulmonary cusp which were 1.5 x 1.5 cm and 0.7 x 0.5 cm in size. The cysts were resected and the pulmonary cusp was plicated. Histologically, the wall of the cysts was consisted thick valvular tissues. No pulmonary valve pressure gradient was detected with the echocardiography following the operation. PMID- 8468846 TI - [Simultaneous operation of Cabrol's operation and sternal turnover with rectus abdominal flap]. AB - We performed simultaneous operation of sternal turnover and Cabrol operation for a 28-year-old man, who had 3rd grade funnel chest and annuloaortic ectasia with 3rd grade aortic regurgitation. We think when both annuloaortic ectasia and funnel chest are indicated for operation, simultaneous operation is to be considered and the combination of Cabrol operation and sternal turnover with rectus abdominal flap is the best procedure. PMID- 8468847 TI - [A case report of combined aortic and mitral regurgitation associated with ankylosing spondylitis]. AB - We reported a case of ankylosing spondylitis which successfully underwent aortic valve replacement for combined aortic and mitral regurgitation. A 42-year-old man was admitted with symptoms of shortness of breath and anginal pain. He was previously diagnosed ankylosing spondylitis by an orthopedician A grade III/VI to and fro murmur was audible at the left sternal border. Retrograde aortography revealed severe aortic regurgitation and mild mitral regurgitation. Cardiac catheterization showed moderately pulmonary hypertension and high pulmonary artery wedge pressure. He underwent aortic valve replacement with SJM prosthetic valve. His postoperative course was uneventful. In Japan, ankylosing spondylitis is rare disease, and cardiac lesions associated with these conditions is seldom met to us. The surgical problems and management of these lesions are discussed. PMID- 8468848 TI - [Successful repair of partial atrioventricular septal defect in a 70-year-old female patient]. AB - A 70-year-old female with partial atrioventricular septal defect underwent a total correction of the anomaly. The patient was in NYHA functional class II. Preoperative cardiac catheterization demonstrated a primum-type atrial septal defect through which 33% of left to right shunt occurred and a cleft of mitral valve causing moderate regurgitation. The operative procedure as our routine for this anomaly consisted of suture of mitral septal commissure and closure of atrial septal defect with autologous pericardial patch. Postoperative examination showed satisfactory competence of mitral valve and improved functional capacity. A successful correction for the case aged more than 66 with this anomaly has not been reported so far in Japanese literature. We conclude that surgical treatment should be basically considered for this anomaly in spite of senility. PMID- 8468849 TI - [Quadricuspid aortic valve: a case report and the review of the literature]. AB - We report a case of rare congenital anomaly of quadricuspid aortic valve and coexisting right coronary displacement. A 70-year-old man was admitted to our hospital for heart murmur and ECG abnormality. The trans-esophageal echocardiography and aortography showed moderate aortic stenosis and regurgitation. At the operation, a quadricuspid aortic valve with three equal cusps and one smaller cusp that showed marked calcification and displacement of right coronary orifice were noted. Successful aortic valve replacement and coronary artery bypass grafting were performed and postoperative course was uneventful. PMID- 8468850 TI - [A case of simultaneous bilateral spontaneous pneumothorax]. AB - A 18-year-old man was admitted urgently complaining dyspnea, cyanosis and chest pain. The chest x-ray film revealed simultaneous bilateral pneumothorax. Chest drains were inserted immediately to the both chest cavities. On the 3 rd hospital day, radical operation for spontaneous pneumothorax with synchronous bilateral thoracotomies were performed through both axillary incision. Postoperative course was uneventful. The patient was discharged on the 8 th day after operation. PMID- 8468851 TI - [Excellent late results of total circulatory annuloplasty with absorbable suture for the repair of mitral regurgitation of atrioventricular septal defects in children]. AB - We treated 15 children with atrioventricular septal defects (6 complete type and 9 incomplete type) using total circulatory annuloplasty for mitral regurgitation. In 14 patients, total circulatory annuloplasty was performed with absorbable suture and in one patient with polypropylene suture. Operative death was one patient associated with tetralogy of Fallot and another 14 patients survived. Preoperative mitral regurgitation was grade 1 in one patient, grade 2 in 6 patients and grade 3 in 7 patients. After operation mitral regurgitation reduced to grade 1 in 13 patients and grade 2 in one patient. In the late results, only one patient underwent reoperation for exacerbation of mitral regurgitation. The present data suggested that total circulatory annuloplasty with absorbable suture was very useful technique for the repair of mitral regurgitation of atrioventricular septal defects in children. PMID- 8468852 TI - [The value of omental pedicle flap method for postoperative intractable infection in the field of thoracic surgery]. AB - We present a series of 8 consecutive patients who underwent the omental pedicle flap method in the field of thoracic surgery. Four of them had empyema with bronchopleural fistula and four had mediastinal infection. A pedicle of omentum containing the right gastroepiploic artery was passed through a tunnel in the diaphragm into the empyema cavity or the mediastinal abscess cavity. All eight patients were cured successfully by single-stage procedures. We think this series demonstrates the value of omental pedicle flap method which lacks in symptoms due to defected organ and offers an excellent therapeutic effect with easy operative procedure. And, this method produce a quality of life. Further active application of this method can be expected in the management of chest problems. PMID- 8468853 TI - [Surgical treatment of metastatic lung tumors]. AB - From January 1970 to March 1991, 72 operations in 55 patients (31 males and 24 females) with metastatic lung tumors were performed in our department. Their cumulative survival rates was 25.5% at five years. With analysis of the various prognostic factors, patients both with solitary metastases and without lymph node metastases had a good prognoses. However, even in patients with recurrent lung metastatic tumors, long time survival was achieved with reoperation in two patients. We concluded that reoperation with or without effective chemotherapies was effective in selected patients. PMID- 8468854 TI - [A depression of respiratory function following the cardiopulmonary bypass in infants and children]. AB - Fourty-one patients (2-44 month old) underwent the closure of ventricular septal defect using moderate-hypothermic cardiopulmonary bypass (CPB). The respiratory index (RI) were monitored after CPB, as functional parameters of oxygenation capacity. At 15 min after CPB, there was the increased level in RI (2.22 +/- 0.45; normal value: 0.1-0.37). Thereafter, RI gradually decreased by 90 min after CPB (1.22 +/- 0.19), and again increased reaching peak levels by 12 hrs after ICU entry (2.56 +/- 0.64). The patients who exceed 1.00 at 15 min after CPB (RI-15) remained higher levels in RI compared to less than 1.00 and had the prolonged controlled ventilation. The RI-15 correlated with pulmonary-systemic flow ratio (Qp/Qs) and pulmonary-left ventricular pressure ratio (PA/LV). There was no significant correlation between RI-15 and CPB factors including CPB time, dilution rate, rectal temperature, flow and perfusion pressure. These results suggest that pulmonary dysfunction following the CPB may not be simply occurred by CPB but also involved by preoperative conditions. An increased pulmonary blood flow might be one of important and predictive factor for the depression of oxygenation following the cardiac surgery in infants and children. PMID- 8468855 TI - [Hygienic handling in cardiac surgery]. AB - Some points regarding the hygienic handling in cardiac surgery are mentioned. The sternal infection or mediastinitis is still one of the most important complications after cardiac operation especially when ITA is used for CABG. After we paid much attention to these points, the postoperative sternal infection has decreased obviously. PMID- 8468856 TI - [A new design of annulus sizer]. AB - Reconstruction of the right ventricular outflow tract at the time of total correction of tetralogy of Fallot, the pulmonary valve annulus has been sized with fingers and Hegar dilators at our institute. But it has not always been sized correctly. To preclude such a problem, we designed new annulus sizers which have two cylindrical parts and a flexible handle (100 mm). The cylindrical parts are 40 mm in length, 8 to 30 mm in diameter, and have three lines marked every 10 mm from the end. Adjustment of the line to the valve annulus allows for correct measurement of the size. Moreover, we consider these sizers to be beneficial for annuloplasty of the atrioventricular valve, measurement of the mitral valve area after commissurotomy and the inner diameter of arteries. PMID- 8468857 TI - [Left main coronary artery stenosis following aortic valve replacement using a solid coronary perfusion catheter: report of two cases]. AB - We experienced two cases of iatrogenic left main coronary artery stenosis (IOCS) following double (aortic and mitral) valve replacement (DVR). The solid coronary perfusion catheter may attribute IOCS, with grave consequence. There have been no IOCS since the time we exchanged a solid catheter for a soft one. One case, she was successfully treated percutaneous transluminal coronary angioplasty (PTCA), because she developed angina pectoris about 5 years after PTCA. But she developed angina pectoris again and angiographically left main coronary was severe stenotic. So she was undergone aorto coronary bypass grafting (CABG) to the left anterior descending. The other case, he developed angina pectoris about 3 months after DVR. He was treated with PTCA. Angiographically left mine coronary artery stenosis reduced 50% from 90%. Generally the treatment of IOCS is CABG, but we performed PTCA for 2 patients. Because we thought it was very hazardous for us to perform them open heart surgery. When it is very hazardous to perform patients open heart surgery, they need to be performed PTCA. PMID- 8468858 TI - [Medtronic model 6500 temporary myocardial pacing lead: a report of clinical assessment until three weeks after cardiac surgery]. AB - Medtronic model 6500 heart wire as a right ventricular electrode was assessed in 41 postoperative cases. R-wave amplitude, slew rate, peak-to-peak, output, current, and resistance were measured by Medtronic A-V pacing system analyser, model 5311, for three weeks after open heart surgery. These parameter changed until the 7 th postoperative day, but did not change significantly thereafter. Output and current did not exceed beyond 10 V and 20 mA respectively, where there is limitations of usually available pacemaker. No complication was encountered. These results showed that this heart wire was reliably useful even until 3 weeks after open heart surgery. PMID- 8468860 TI - [Acute aortic dissection without opacification of the false lumen on the initial aortogram: a case report]. AB - A 50-year-old woman was admitted to the intensive care unit 40 min after the onset of severe chest and back pain with consciousness loss. Emergency computed tomography and aortography demonstrated an acute type A dissection without opacification of the false lumen. The patient was initially treated with antihypertensive drugs. Recurrent back pain and bilateral pleural effusion appeared 3 days after onset of the pain. Both the right radial and carotid pulses were reduced. Emergent operation was performed when computed tomography and aortography repeated 5 days after onset of the pain demonstrated the intimal flap in the ascending aorta with the opacified false lumen. The site of intimal tear in the proximal arch was resected and a 26 mm Dacron graft was inserted during deep hypothermia and circulatory arrest. The postoperative course was uneventful. PMID- 8468859 TI - [A case of aortic dissection (DeBakey-I) occurring 20 months after aortic valve replacement]. AB - Simple aortic valve replacement was performed in a 59-year-old man whose ascending aorta was moderately dilated (45 mm) because he had no characteristics of Marfan's syndrome or other connective tissue diseases. However, about 20 months later, reoperation needed to be performed for aortic dissection of DeBakey type I. The pathological findings of the aortic wall obtained at the initial operation revealed cystic medial necrosis. The occurrence of aortic dissection after aortic valve replacement is uncommon but not rare, especially in patients with cystic medial necrosis and/or dilated aortic root. Therefore, in these patients, wrapping or replacement of the ascending aorta may be required at the same time of aortic valve replacement. PMID- 8468861 TI - [Emergent operation of left atrial ball thrombus associated with mitral stenosis]. AB - A 71-year-old woman with old cerebral infarction and arterial obstruction was admitted with the diagnosis of a free floating ball thrombus in the left atrium associated mitral stenosis. The emergent open heart operation was performed for removal of ball thrombus and mitral commissurotomy. The size of ball thrombus was 4.8 x 4.0 x 3.0 cm. Postoperative course was uneventful. PMID- 8468862 TI - [Surgical treatment of aortitis syndrome associated with annuloaortic ectasia and the stenotic lesion of the aortic arch vessels]. AB - A 37-year-old woman was admitted to our hospital for treatment of aortitis syndrome. Her aortogram showed critical stenosis of the innominate artery, occlusion of other arch vessels, and annuloaortic ectasia (AAE). We performed endarterectomy and patch plasty to the innominate artery using a saphenous vein graft. Graft replacement of the ascending aorta and AVR (modified Wheat's operation) were also performed at one stage. Deep hypothermic cerebral circulatory arrest was used as a method for cerebral protection. During operation, the lowest rectal temperature was 17 degrees C and the cerebral circulatory arrest time was 36 min. The postoperative course has been uneventful. In a postoperative aortogram, the innominate artery was well perfused. She has been free of complaint and been doing well for 2 years since the operation. PMID- 8468863 TI - [A case report of one-staged surgery for annuloaortic ectasia associated with atypical coarctation of the aorta]. AB - A 33-year-old man admitted to our hospital with an episode of chest discomfort and dyspnea. UCG, CT, MRI and DSA disclosed an annuloaortic ectasia with grade 3 aortic regurgitation and atypical coarctation of the aorta. Cabrol operation was performed with simultaneous graft bypass using a woven Dacron prosthesis between the ascending aorta and the abdominal aorta. The course of the bypass graft was arranged to pass behind the rectal muscle without laparotomy and major collateral vessels of the thorax could been kept without thoracotomy. There are only 10 reported cases of annuloaortic ectasia associated with atypical coarctation of the aorta in Japan. This is the second successful case report of one-stage surgery to the complicated cardiovascular disease. PMID- 8468864 TI - [A case of pseudoaneurysm of the thoracic aorta with Behcet's disease]. AB - A 54-year-old female with incomplete type of Behcet's disease was operated on because of impending rupture of the thoracic aneurysm. There was a saccular pseudoaneurysm below the left subclavian artery, and a punched out lesion of the aorta was recognized. The defect of the aortic wall was closed with a PTFE patch. Before and after the operation, we have given prednisolone. The postoperative course was uneventful. Two years later, there was no recurrence of pseudoaneurysm near the PTFE patch. In many reports, aneurysms of Behcet's disease are saccular pseudoaneurysms, and have high incidence of complications about anastomosis postoperatively. We need a further follow-up about this patient. PMID- 8468865 TI - [A case of giant dumbbell tumor treated by one-stage operation]. AB - A 39-year-old woman who had been diagnosed as having von Recklinghausen's disease came to our hospital due to numbness of the right fingers. A chest roentgenogram indicated a mass in the right upper thoracic cavity and MRI showed this mass to be a dumbbell shaped tumor connected to the spinal canal. Because we could secured the extension and invasion of the tumor by MRI, we could remove the tumor by a one-stage operation. PMID- 8468866 TI - [A case of angina pectoris and aortic regurgitation combined with thymoma]. AB - A case of a 72-year-old female with obstruction of LAD, stenosis of RCA, aortic regurgitation in moderate degree and an anterior mediastinal mass of 7 cm in diameter, is reported. Coronary artery bypass grafting, aortic valve replacement and thymectomy were simultaneously performed. On microscopic examination, the tumor was diagnosed as a mixed typed thymoma in the first stage of Masaoka's classification. She was making satisfactory progress without recurrence, after the operation. There was no case has been reported previously in the world in which simultaneous operations were performed for angina pectoris, aortic regurgitation and thymoma. PMID- 8468867 TI - [A case of two-chambered right ventricle associated with severe pulmonary valve regurgitation]. AB - A 40-year-old female was admitted to the hospital with the chief complaints of dyspnea on effort. Echocardiography and cardiac catheterization revealed an abnormal muscle bundle in the right ventricle which divided right ventricle into two chambers with the pressure gradient of 86 mmHg between them. And severe regurgitation associated with hypoplastic pulmonary valve and ventricular septal defect were noted. We removed the abnormal muscle bundle through the right atrial and ventricular approach, and pulmonary valve replacement and VSD closure were carried out. We report a case of two-chambered right ventricle with severe pulmonary valve regurgitation because of its rarity. PMID- 8468868 TI - [A case of myasthenia gravis developing after resection of non-invasive thymoma]. AB - The patient was a 79-year-old male. On CT of the chest, a mass shadow of the anterior mediastinum was found. He did not complain of symptoms, and there were no clinical signs of myasthenia gravis (MG) before surgery. The tumor and the thymus was completely resected. The pathological diagnosis was non-invasive thymoma, and his postoperative course was satisfactory. However, 2 months after the operation, the patient complained of ptosis, diplopia, dysphagia, and muscle weakness, which deteriorated rapidly. The titer of anti-acetylcholine receptor antibody was high at 91.0 nmol/l. By medication of anti-cholinesterase drug and predonin, the symptoms of MG improved. After resection of thymoma, postoperative follow-up with considering the possibility of postoperative MG is necessary. PMID- 8468869 TI - [A surgical case report of severe valvular aortic stenosis with atrial septal defect in a 78-year-old female]. AB - We have experienced open heart surgery of severe valvular aortic stenosis associated with atrial septal defect in a 78-year-old female patient. This is the oldest case in Japanese literature. Because balloon valvuloplasty can not produce improvement in hemodynamic and clinical status, open heart surgery was performed as the final decision. The operative procedure consisted of aortic valve replacement with a 19 mm St. Jude Medical valve and direct closure of atrial septal defect. Postoperative course was excellent. The patient is doing well at the two years and three months of follow-up period. PMID- 8468870 TI - Septic shock: a review and update for the emergency department clinician. PMID- 8468871 TI - Critical pathways in the emergency department. AB - The actual development of the CP is an easy undertaking that an experienced emergency nurse can accomplish. The important points to remember are as follows: (1) include all disciplines that provide patient care in the development of the CP, (2) use realistic time frames (i.e., those currently found to be true in the emergency department, not those that are perceived to be ideal), (3) thoroughly educate the staff about the value of the CP in the emergency department, and, finally, (4) make sure that staff members know how to document variances. CPs in the emergency department give physicians and nurses common ground on which to negotiate patient care management more efficiently and effectively. They are a logical way to bring case management into the acute care setting. With the cost of ED visits continually rising, patient acuity levels increasing, and resources declining, expedient, coordinated, multidisciplinary action is crucial in giving total quality care to each patient. PMID- 8468872 TI - Implications of the consolidated Omnibus Budget Reconciliation "antidumping" legislation for emergency nurses. AB - Although the original intent of the law is to protect the indigent, the statute applies to any situation in which a patient is denied care or transferred to another facility before being medically stabilized. The data thus far indicate that financial motives may be only partially responsible for alleged COBRA violations and that other health care system issues are involved. Patient "dumping" may become better camouflaged against federal and state scrutiny, but until these other issues are identified and addressed dumping may continue to occur for a variety of reasons. To avoid the appearance of dumping, the emergency nurse and physician should meticulously record all aspects of every patient transfer. Particular attention should be given to documenting patient stability at the time of transfer, the risks versus benefits of the transfer, and the communication with and acceptance of the patient by the receiving facility. Emergency nurses, directors of nursing, and nursing quality assurance or risk managers should all be familiar with the COBRA requirements. For further information on the interpretation and application of COBRA, contact your state's acute care facility licensing authority or one of the HCFA Regional Offices listed in the Appendix. PMID- 8468873 TI - Will trauma centers become extinct? A review of factors affecting trauma center financial viability. PMID- 8468874 TI - The accuracy of the tympanic membrane thermometer in detecting fever in infants aged 3 months and younger in the emergency department setting. AB - OBJECTIVE: To evaluate the accuracy of fever detection using the tympanic membrane thermometer in infants age 3 months and younger in a general ED clinical setting. DESIGN: Retrospective analysis of sequential tympanic and rectal temperature readings for sensitivity, specificity, and predictive values. SUBJECTS: One hundred two infants, aged 3 months and younger, coming to the emergency department from January 1991 to July 1991. RESULTS: With fever defined as a temperature of 99.6 degrees F or greater by tympanic thermometer or 100.6 degrees F or greater by rectal thermometer, the tympanic thermometer had an overall specificity for fever detection of 88%. Sensitivity was 90% or higher in the 2-month-old and younger age groups and 66% in the 3-month-old age group. Negative predictive values were 90% and greater and positive predictive values ranged from 60% to 66%. CONCLUSION: The tympanic membrane thermometer provided a reliable temperature reading in a high percentage of the sample population when the infant was afebrile. It was less reliable in detecting the presence of fever in this same age group. Febrile temperature readings obtained by the tympanic membrane thermometer within this age group may need to be compared with a rectal mode reading to accurately determine the presence of fever. PMID- 8468875 TI - Blood glucose monitoring at triage. AB - OBJECTIVE: To examine the use of a blood glucose monitor (BGM) on nursing and medical care, treatment time, and disposition time for patients in an ED triage. DESIGN: Experimental design. Individuals assigned to the experimental group had their blood glucose tested by finger stick in the triage area. The blood glucose level was made known to the triage nurse and/or the nurse caring for the patient in the emergency department proper. The investigator observed the nursing care, nursing and medical interventions and times. The control group underwent triage as usual, with no finger stick. SUBJECTS: Individuals with a history of diabetes and at least 18 years old were randomly assigned to the experimental or control group. The participants were 30 men and 38 women. RESULTS: Early knowledge of the patient's blood glucose level as determined by BGM affected time and implementation of nursing care. Three nursing interventions were significantly different between the groups: assessment, chi 2(1,N = 68) = 10.15, p < 0.001; consult a physician, chi 2(1,N = 68) = 17.58, p < 0.001; and order stat laboratory tests, chi 2(1,N = 68) = 13.09 = p < 0.001. The time the nurse intervened was significantly less for the experimental (24 minutes) than for the control (164.3 minutes) group (t[65] = -7.05, p < 0.001). Medical treatment time was significantly less for the experimental group (89.2 minutes) than for the control group (165.5 minutes) t[64] = -2.07, p = 0.05). Disposition time did not differ between groups. CONCLUSIONS: Data support the use of a BGM as a fast, accurate means of obtaining blood glucose levels. The nurses consulted with a physician, ordered stat laboratory tests for verification, and assessed the experimental patients more frequently than the control patients. Medical treatment time was also shorter for the experimental group. A BGM is an important source of data with which emergency nurses initiate care, at a fraction (3%) of conventional laboratory cost. PMID- 8468876 TI - Diagnostic and characteristic signs of illness and injury. PMID- 8468877 TI - Recognition and treatment of neuroleptic malignant syndrome. AB - NMS remains a serious and unpredictable reaction to central nervous system dopamine blockade. Use of the more recent, flexible definition of NMS will ensure that patients with this syndrome receive prompt effective diagnosis and treatment. Supportive care, discontinuation of the neuroleptic drug, and administration of bromocriptine are the keys to appropriate management. For patients with hypertension, nifedipine may be a useful alternative or adjunctive treatment. Because these patients may not be able to communicate, the role of the emergency nurse includes not only administration of supportive and pharmacologic care but also reassurance that this frightening disorder is treatable, with improvement likely within 1 day. PMID- 8468878 TI - Emergency department labor and delivery records. PMID- 8468879 TI - Monitoring patients who receive conscious sedation in the emergency department. PMID- 8468880 TI - The Americans with Disabilities Act and the role of the registered nurse with a disability. PMID- 8468881 TI - Self-study packets: an in-service strategy for today's emergency department. AB - The self-study program has been a great success. Staff seized the opportunity for "hands-on," nonthreatening learning. The fear of asking questions and appearing less knowledgeable than peers in a group setting is removed, and new employees are grateful for the rapid accessibility of concise reference material. Everyone enjoys the freedom of fitting the in-service program into a routine day, rather than trying to adapt to a set time. Last, but not least, management reaps to the benefit of a program that satisfies the expectations of regulatory agencies and is virtually cost-free. PMID- 8468882 TI - Calculating continuous medication infusions: the "50 cc method". PMID- 8468883 TI - Trauma system problems: using the tools of quality improvement to find solutions. PMID- 8468884 TI - A 20-year-old man with neck and chest pain and discomfort with breathing. PMID- 8468885 TI - Just like Kathy Haley, Columbus, Ohio. Interview by Marlene Jezierski. PMID- 8468886 TI - Words to the wise. PMID- 8468887 TI - Journey of a layoff: one emergency department nurse manager's story. PMID- 8468888 TI - International update: alternative treatment for common but dangerous acetaminophen overdoses. PMID- 8468889 TI - The ethics of exclusion and the myth of control. PMID- 8468890 TI - A look at our new emergency department. Shadyside Hospital, Pittsburgh, Pennsylvania. PMID- 8468891 TI - Two licenses for advanced practice nurses? ENA thinks not. PMID- 8468892 TI - Increased incidence of neurocysticercosis after contact with immigrants from endemic countries. PMID- 8468893 TI - Lack of sedation for cardiopulmonary bypass questioned. PMID- 8468894 TI - A 43-year-old man with syncopal episode and bradycardia 2 weeks after a motor vehicle crash. PMID- 8468895 TI - Acute ethylene glycol poisoning. PMID- 8468896 TI - Stresses and coping mechanisms: a report of interviews with eleven emergency department nurse managers. PMID- 8468897 TI - Automated external defibrillators: prehospital use in advanced cardiac life support. AB - It is evident that AEDs may be used by minimally trained first responders to terminate VF safely and rapidly in victims of out-of-hospital cardiac arrest. To enhance patient survival of out-of-hospital VF, there must be coordination between AED-trained first responders and ACLS providers. PMID- 8468898 TI - Comrades in abuse. PMID- 8468899 TI - Nonassignment provisions as cost control. PMID- 8468900 TI - Is your CPR training up to date? PMID- 8468901 TI - Infant cardiorespiratory monitor burn. PMID- 8468902 TI - Reflex sympathetic dystrophy. PMID- 8468903 TI - Recent-onset temporal lobe seizures caused by an unusual intracerebral mass. PMID- 8468904 TI - Alcohol-related mortality in Kansas, 1990. PMID- 8468905 TI - More on the Mennonites. PMID- 8468906 TI - Case management: are we ready? PMID- 8468907 TI - Case management: care across the continuum. PMID- 8468908 TI - Collaborative care in the acute care setting. PMID- 8468909 TI - Nursing case management in a rural setting. PMID- 8468910 TI - Molecular approaches to nephrology: prospects in diagnosis and management. Bari, Italy, March 19-22, 1992. Proceedings. PMID- 8468911 TI - Angiotensin II as a hypertrophogenic cytokine for proximal tubular cells. PMID- 8468912 TI - Gene transfer into the mammalian kidney: first steps towards renal gene therapy. AB - In this review we discuss two strategies for successful retrovirally-mediated transfer (transduction) of a reporter gene (bacterial beta-galactosidase) into the mammalian kidney. Retroviruses only integrate into dividing cells, but the adult kidney has a very low cell turnover. One approach used is the rapidly dividing metanephros, or precursor of the adult kidney, as a target for proviral integration. After infection and microtransplantation of fragments of this tissue into the renal cortex of neonatal mice, the implants grew and developed within the host kidney and reporter gene expression was located in glomerular and interstitial cells. A similar approach has been used by other investigators to grow genetically-engineered metanephros in a subcapsular location in the kidney. However, access of the gene product to the parenchyma of the kidney may be limited using this approach. A second strategy was to induce renal tubular cell replication by causing nephrotoxic damage with a folic acid injection. This created a 'biological window' in which a specific cell population, that is, tubular cells, was targeted for retroviral infection. One to four weeks later foci of tubular cells were found to express the reporter gene product. In both models, 50 to 90% of the experiments showed evidence of proviral integration as judged by the presence of a 559 base-pair DNA fragment amplified by the polymerase chain reaction. This persisted for four to seven weeks, the limit of the period of observation. PMID- 8468913 TI - Prospects for anti-rejection therapies based upon CD8-dependent immunoregulation. AB - In this article we propose that anti-rejection immunotherapies for countering acute allograft rejection can be designed around manipulation of the cell surface phenotype of alloantigen-presenting cells (allo-APCs) in ways that convert them from T cell activators to inhibitors. It is further suggested that a class of molecules, termed "coinhibitors," can be defined that carry out this APC conversion process. Data are summarized indicating that the human lymphoid cell surface molecule CD8 has such a trans-coinhibitor function which is in addition to the cis-coreceptor and adhesin functions traditionally ascribed to it. Antisense and sense gene transfer studies indicate that CD8 on the surface of allo-APCs leads to inhibition of allospecific T cell responders. We have explored the possibility of using protein, rather than gene, transfer as a therapeutic strategy for delivering CD8 to APC surfaces. Two membrane-binding variants of CD8 have been assembled to show retention of the coinhibitor function of native CD8. Immunotherapeutic possibilities associated with these chimeric CD8 polypeptides in the clinical context of renal and other organ transplantation are considered. PMID- 8468914 TI - Differential in situ expression of cytokine genes in human renal transplantation. PMID- 8468915 TI - Analysis of T cell lines from rejecting renal allografts. AB - Acute rejection after renal allotransplantation is characterized by the presence of a mononuclear cell infiltrate in the interstitium with involvement of tubuli. In a previous study on renal histology we showed that tubular damage by graft infiltrating cells (GIC) is a sign of clinically significant rejection. We cultured proximal tubular epithelial cells (PTEC) and T cells bearing the interleukin 2 (IL-2) receptor from biopsies after transplantation. In vitro outgrowth of T cells from the biopsy was significantly (P = 0.0014) related to histological signs of graft rejection. Of the T cell lines generated from 25 biopsies, only five lines showed no or low cytotoxicity against donor PTEC. Three cell lines were cytotoxic towards donor PTEC, but not against PHA stimulated donor splenocytes, suggesting tissue specificity of GIC. Treatment of PTEC with interferon (IFN) gamma for 72 hours to upregulate MHC class I and to induce MHC class II expression did not necessarily result in an increased susceptibility to lysis. However, three PTEC lines displayed an increment of susceptibility to lysis after IFN gamma treatment. Analysis of one T cell line from the same graft revealed a high percentage of CD4 positive cells, compatible with a class II restricted cytotoxicity. This was confirmed by blocking experiments using anti CD4, anti-CD8, anti-class I, and anti-class II antibodies. Blocking experiments were done with 12 of these 25 lines. Anti-CD3 and anti-CD18 antibodies inhibited cytotoxicity in every case, showing that cytotoxicity was T cell mediated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468916 TI - Induction of interleukin-1 during hemodialysis. PMID- 8468917 TI - Induction of mRNA for tumor necrosis factor alpha in hemodialysis. PMID- 8468918 TI - Influence of hemodialysis on interleukin-6 production and gene expression by peripheral blood mononuclear cells. PMID- 8468919 TI - Role of platelet activating factor in hemodialysis. AB - A complex array of inflammatory mediators are generated as a consequence of blood contact with hemodialysis (HD) membranes. Beside complement activation, other mediators are involved in cell activation, and are thought possibly to be responsible for early and long-term multiple changes in immunity infection, hypercatabolism, beta 2-microglobulin generation and hemostatic mechanisms. Previous studies from our laboratories have established platelet activating factor (PAF) as one of the mediators generated by complement-dependent or independent mechanisms of cell interaction with hemodialysis membranes. Recent studies on the production of PAF from endotoxin-primed polymorphonuclear neutrophils in a closed miniaturized circuit, and on the effect of PAF in mediating endotoxin- and cytokine-induced leukocyte adherence to HD membranes, highlight so far undescribed new roles of this mediator in biocompatibility. PMID- 8468920 TI - Positional cloning approach to the dominant polycystic kidney disease gene, PKD1. AB - Positional cloning is a powerful strategy for identifying the site of disease producing mutations when the underlying biochemical defect is unknown. The approach also offers new methods for the presymptomatic diagnosis of genetic disease. Using these methods we have localized the PKD1 gene, mutated in the majority of PKD1 families, to a small (500 kb) segment of chromosome 16, band p13.3. Virtually all of this interval has been cloned in cosmids and lambda bacteriophage. Over 20 sets of non-overlapping cDNA clones have been isolated from the region. Sequence and mutational analyses are currently underway. In addition, a set of polymorphic clones has been identified for presymptomatic diagnosis. Included in this set are several highly variable [CA]n microsatellite repeats. These highly informative markers can be rapidly assayed from a small amount of genomic DNA using the polymerase chain reaction. Despite these advances, presymptomatic diagnosis cannot be established with certainty in many families. However, identification of the PKD1 gene itself will eventually allow diagnosis by direct detection of mutations. PMID- 8468921 TI - Cytokines and mesangial cells. AB - Hyperplasia of mesangial cells (MCs) precedes or accompanies progressive glomerular scarring, as is seen in chronic glomerulonephritis and diabetic glomerulosclerosis. The mechanisms causing in vivo MC proliferation and production of extracellular matrix (ECM) are incompletely understood. Cell culture studies have demonstrated that MCs produce as well as react to various polypeptide cytokines. Thus, MCs have the potential to generate soluble mediators which can, in a paracrine fashion, attract and activate inflammatory cells (platelets, monocyte-macrophages, granulocytes), for example by IL-6, IL-8, MCP-1 and GM-CSF, and exert autocrine effects on MCs themselves, such as by promoting MC proliferation (by PDGF, IL-1, IL-6) or ECM production (by TGF-beta, IL-1). Recent in vitro results have revealed that specific non-soluble ECM components (collagen III, IV; laminin) also affect MC behavior with regard to adhesion, cell replication, ECM production as well as their response to cytokines. The latter effect appears to be mediated by alterations of cytokine receptor expression on MCs in the presence of the ECM components. "Cross-talk" between MCs, cytokines, ECM and inflammatory cells is likely to be of great importance in the regulation of the MC phenotype and may play a prominent role in the initiation and progression of glomerular inflammation. First in vivo findings in rats with experimental glomerular disease and in kidney biopsies from patients with glomerulonephritis have supported this concept by demonstrating abnormal MC expression of cytokines, their receptors and ECM proteins. These MC products may promote the recruitment and activation of inflammatory cells and perpetuate MC proliferation as well as ECM build-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468922 TI - Immunogenetic findings in glomerulonephritis. AB - In the 19th century, several authors recognized that some renal diseases tend to run in families. Alport pointed to the constellation of nephritic urinary sediment, hearing loss and progression into renal failure. Today this is recognized to result from abnormal basement membrane (BM) collagen synthesis. Recently it has been recognized, however, that other forms of glomerulonephritis may also run in families. In about 10% of patients with glomerulonephritis one or more sibling also suffers from glomerulonephritis. Genetically determined derangements of immune regulation may play a role in the genesis of primary chronic glomerulonephritis. Potentially associated immunogenetic abnormalities include inherited defects of the complement system, increased prevalence of certain HLA-types, altered frequencies of polymorphisms in immunoglobulins and TCR genes and others. This overview summarizes immunogenetic studies performed in patients with glomerulonephritis with special emphasis on patients with mesangial IgA GN. PMID- 8468923 TI - Effect of cytokines on the cytoskeleton of resident glomerular cells. AB - Resident glomerular cells have complex cytoskeletal organizations relevant to maintaining functional and structural integrity. The ability of cells to change shape, develop coordinate directed movements, replicate and interact with contiguous cells or extracellular matrix depends on cytoskeletal functions. Several cytokines directly or indirectly change cytoskeletal organization. Cytokines may alter cytoskeletal organization in cultured glomerular epithelial and mesangial cells and vascular endothelial cells mainly by mechanisms involving production of secondary mediators, such as PAF and leukotrienes that stimulate cell contraction, or PGE2 and PGI2 that stimulate cell relaxation. Consequent assembly and disassembly of microfilaments leads to functional responses of cells that may account for the physiopathological changes induced by cytokines in vivo. PMID- 8468924 TI - Modulation of renal production of C3 by proinflammatory cytokines. PMID- 8468925 TI - Cytokine mRNA expression by cultured rat mesangial cells after contact with environmental lectins. AB - We previously demonstrated that gliadin, a lectinic component of gluten, induces IgA mesangial deposits in orally immunized mice, binds in vitro polymeric IgA and cultured rat mesangial cells modulating their arachidonic acid metabolism. We investigated the effects of gliadin and other environmental lectins on some mesangial cell functions, including synthesis and release of cytokines and lipid mediators. Several lectins, particularly gliadin, affected the mRNA expression of c-myc and c-fos, two proto-oncogenes involved in the transcriptional enhancement of the gene cascade, which are markers of cell growth, differentiation and mitosis. Lectins modulated the ability of cultured rat mesangial cells to express mRNA for cytokines involved in the inflammation and in the regulation of the immune response. TNF-alpha and IL-6 mRNA transcription were enhanced by gliadin and other lectins, and TNF release was variably increased. Conversely, IL-1 production was less affected or slightly depressed. PAF production was not detectable while PGE2 was generally reduced and TXB2 enhanced. Gliadin was one of the lectins most active on the mesangial cells, and its effects were reversed by the addition of N-Acetylglucosamine, a sugar specific for some lectinic bindings, suggesting a carbohydrate interaction. The effects of the various lectins were distinct and only partially convergent, ruling out an aspecific mesangial cell activation. These data suggest that lectins might interfere with mesangial cell functions and modify the mesangial cell homeostasis. PMID- 8468926 TI - Factors involved in the regulation of mesangial cell proliferation in vitro and in vivo. AB - One of the central features of many human glomerular diseases is the proliferation of the smooth muscle cell-like mesangial cells. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. To investigate the regulation of mesangial cell proliferation in vivo we have studied the mesangioproliferative glomerulonephritis that is induced by injection of antibody directed against the Thy 1.1 antigen on the mesangial cell surface in rats. In this review, we discuss the role of three cytokines in the mesangioproliferative response, namely platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokines are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to exert both paracrine and autocrine regulatory functions on mesangial cells. In vivo studies show that PDGF, bFGF and TGF-beta participate in either the mesangial cell proliferation or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody. Based on currently available data we propose that bFGF may participate in the initiation, PDGF in the maintenance, and TGF-beta in the resolution of mesangial cell proliferation in vivo. Further analysis of the mitogens operative in vivo may ultimately result in the design of new therapeutic strategies to treat progressive glomerular mesangioproliferative diseases. PMID- 8468927 TI - Studies by competitive PCR of glomerulosclerosis in growth hormone transgenic mice. AB - We have shown that the glomerulosclerotic lesions of mice transgenic for bovine growth hormone (bGH mice) consisted of a change in the phenotype of glomerular collagens and an elevation of the mRNAs for these collagens in whole kidney. The purpose of this study was to determine whether these phenotypic and quantitative changes were present in the glomeruli. We used the increased sensitivity afforded by reverse transcription followed by the polymerase chain reaction (RT-PCR) to detect type I collagen mRNA and a quantitative PCR assay to quantitate type IV collagen mRNA in microdissected glomeruli. There was a six- to eightfold increase in alpha 1IV collagen mRNA in the glomeruli of bGh mice. alpha 1(I) collagen mRNA was present in glomeruli of bGH mice, which is consistent with our previous findings that the sclerotic mesangium contained type I collagen peptides by immunofluorescence microscopy. Normal glomeruli did not contain detectable amounts of alpha 1I collagen mRNA. In summary, we found a phenotypic change in glomeruli of mice transgenic for bGH consisting of increased type IV collagen mRNA levels and the appearance of type I collagen mRNA. Thus, the development of glomerulosclerosis appeared to be at least partially regulated at a pretranslational level. PMID- 8468928 TI - Cytokines, mesangial cell activation and glomerular injury. PMID- 8468929 TI - Role of interleukin-6 in the progression of mesangial proliferative glomerulonephritis. AB - Mesangial proliferative glomerulonephritis (mesPGN) is histologically characterized by proliferation of mesangial cells (MC), suggesting the involvement of a growth factor for MC in the pathogenesis of mesPGN. We have previously shown that interleukin-6 (IL-6) induces proliferation of cultured rat mesangial cells, and urine samples from patients with IgA nephropathy contain high level of IL-6 activity. We have also demonstrated that transgenic mice carrying a human IL-6 genomic gene showed severe mesangial proliferation and matrix enlargement. Urinary samples of patients with lupus nephritis as well as IgA nephropathy contain significant IL-6 activity. Over a ten month follow-up, a positive correlation between the urinary IL-6 and pathological score was observed. Hence, measurement of urinary IL-6 can be used as a good indicator for monitoring IgA nephropathy and lupus nephritis. Using RT-PCR methods, IL-6 mRNA was detected in the glomeruli of renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis. PMID- 8468930 TI - Role of endothelin in glomerular injury. PMID- 8468931 TI - The intercrine superfamily and renal disease. PMID- 8468932 TI - Platelet-derived growth factor and proliferative glomerulonephritis. PMID- 8468933 TI - MHC gene polymorphism in primary IgA nephropathy. PMID- 8468934 TI - Glomerulosclerosis in mice transgenic for native or mutated bovine growth hormone gene. AB - Mice transgenic for bovine growth hormone (bGH) develop an increase in body weight and glomerular lesions characterized by a disproportionate increment in glomerular volume and progressive mesangial sclerosis. The relationship between glomerular size and body growth in bGH mice was further investigated by examining mice transgenic for a mutated GH gene (bGH-m11) which failed to enhance body growth. The glomeruli in bGH-m11 mice exhibited an increase in size and glomerulosclerosis comparable to those found in bGH mice. The levels of alpha 1 type IV collagen mRNA, as measured by the competitive polymerase chain reaction in isolated microdissected glomeruli, were markedly elevated in mice transgenic for both bGH and bGH-m11 genes. These data suggest that body growth on one hand, and glomerular hypertrophy and sclerosis on the other hand, are mediated by different portions of GH or different second messenger signaling systems. PMID- 8468935 TI - Expression of 5-lipoxygenase and 5-lipoxygenase activation protein in glomerulonephritis. AB - The gene transcription of 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in renal tissue of patients with IgA nephropathy and mesangial proliferative glomerulonephritis were analyzed by amplification of reverse transcribed mRNA with polymerase chain reaction (PCR). The level of expression was determined by analysis of the PCR products of 5-LO, FLAP, and beta-actin. Forty percent of the patients expressed both 5-LO and FLAP. Relative to beta actin, FLAP expression (0.42 +/- 0.21) was higher than 5-LO (0.14 +/- 0.10). Comparison of clinical data showed that patients who expressed 5-LO and FLAP had a lower glomerular filtration rate and an increased level of blood urea nitrogen, serum creatinine, and proteinuria. The results suggest arachidonic acid metabolism by inflammatory cells in renal tissue may play an important role in human glomerulonephritis. PMID- 8468936 TI - [The nursing concept in a psychiatric hospital department]. PMID- 8468937 TI - [Recognizing and supporting abilities]. PMID- 8468938 TI - [Aggression-promoting structures. How can one counter them?]. PMID- 8468939 TI - [Elke Felgner, psychiatric nurse]. PMID- 8468940 TI - [Typically female. Nursing in the 19th century]. PMID- 8468941 TI - [Shift work and nurses' health]. PMID- 8468942 TI - [Working times for better quality of work and life]. PMID- 8468943 TI - [Health establishments in Scandinavia. Report from a study trip by the 1991/92 nursing seminar of the Bavarian county nursing association]. PMID- 8468944 TI - [Juridic problems during training. Report from a student seminar]. PMID- 8468945 TI - [The transfer visit]. PMID- 8468946 TI - [Pediatric nurse in a boarding school for disabled children]. PMID- 8468947 TI - [Difficult search for employment. Unemployed nurses]. PMID- 8468948 TI - [Temporary firms. Position of Parmed Ltd. Legislative conditions basically improved]. PMID- 8468949 TI - [Research and communication: a path to follow]. PMID- 8468950 TI - [Genetic exploits under the magnifying lens. Predictive medicine: what are the stakes?]. PMID- 8468951 TI - [Early diagnosis. The right to know ... or to ignore]. PMID- 8468952 TI - [Ethical questions in neonatology. Indispensable: the spirit of discussion]. PMID- 8468953 TI - [North-South solidarity. Listen to the women]. PMID- 8468954 TI - [Attention, polluters!]. PMID- 8468956 TI - [Sudden infant death--a report. "... and did not wake up again"]. PMID- 8468955 TI - [Transitory dispositions of the CRS. Should they be abolished without an alternative?]. PMID- 8468957 TI - [Discharge planning for new mothers. At home everything is different]. PMID- 8468958 TI - [A professional trip through Israel. Good health care--self-assured nurses]. PMID- 8468959 TI - [Execution of the new educational rules: first a position statement]. PMID- 8468960 TI - [Illness experienced on one's own skin. When the nurse becomes a patient]. PMID- 8468961 TI - Buyers' guide 1993. PMID- 8468962 TI - Liver transplantation in South Carolina. PMID- 8468963 TI - Acute renal failure: pathology and prevention. PMID- 8468964 TI - Anterior cervical diskectomy and fusion in a community hospital setting. PMID- 8468965 TI - Rebuilding a hospital in a developing country. AB - The volunteer group had a successful trip overall. The local medical facility underwent substantial physical improvements. Sanitation in a limited area was augmented. There was a significant measure of "good will" benefit from the standpoint of an American venture into a developing nation. The National Guard units involved received enhanced training and improved their abilities to deploy. On a personal note, those of us who were given the opportunity to travel to and work in such an austere location gained a sincere appreciation for the genuine blessings of American standards of living. PMID- 8468966 TI - "The great American fraud". PMID- 8468967 TI - Health education: state of the art. PMID- 8468968 TI - Accomplishments in comprehensive school health education. PMID- 8468969 TI - Comprehensive school health education: barriers and opportunities. PMID- 8468970 TI - Today's education policy environment. PMID- 8468971 TI - Health policy reform and comprehensive school health education: the need for an effective partnership. AB - This article offers a framework for considering how health care reform issues will impact the success of any national movement to implement Comprehensive School Health Education and the potential role that CSHE proponents can play in advocating reforms congruent with CSHE goals. The effectiveness of the CSHE movement within this arena will depend largely on its ability to critically self diagnose its potential contributions to short-term and long-term positive health outcomes, and on its ability to join forces in ensuring that a variety of health, educational, and social services are made available in nontraditional sites- particularly schools--that are able to reach children and their families. An important step will be to expand the availability of Comprehensive School Health Education throughout the country: only one-half of all states currently mandate Comprehensive School Health Education programs, and implementation is spotty in some of these states. Another boost for the potential role of CSHE proponents can be found in the Year 2000 health objectives, of which more than one-third of 300 objectives geared to promoting health and disease prevention are devoted to the health behavior of school-age children and youth. Many of these objectives can be achieved directly or indirectly in schools, contingent upon appropriate financing and the establishment of CSHE goals as priorities at the policymaking level. An important factor will be the ability of the CSHE movement to provide its programs in the most cost-effective and cost-efficient manner, possibly including redeployment of staff and relocating resources as needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8468972 TI - Postoperative outcome following thoracotomy in the pediatric oncology patient with diminished pulmonary function. AB - Surgical resection of pulmonary metastatic disease is often indicated in pediatric malignancies. Although several adult studies document increased postoperative morbidity in adults with diminished pulmonary function, there is little information in the pediatric population or in patients with restrictive lung disease. We reviewed the postoperative course following thoracotomy in patients with diminished pulmonary function (FVC, FEV1, or TLC less than 80% predicted). Thirty-two thoracotomies were performed in 19 patients. The preoperative FVC (% predicted) was 68 +/- 3.6 with a postoperative value of 60 +/ 2.4 (P < 0.01). The preoperative FEV1 was 69 +/- 4.2 with a postoperative value of 60 +/- 3.8 (P < 0.01). Although there was a significant drop in pulmonary function tests (PFTs) following surgery, there was not a significantly greater loss when comparing patients with mild, moderate, and severe disease. When considering postoperative morbidity, there were 3 events (prolonged oxygen requirement, need for postoperative ventilation, or persistent air leak) following 20 surgeries in patients with mild preoperative respiratory dysfunction, 5 events (including one death) in the 7 patients with moderate dysfunction, and 3 events following 5 surgeries in patients with severe dysfunction. There was no correlation with a decrease in any specific PFT and the occurrence of postoperative morbidity. Our limited review suggests that aggressive surgical treatment of metastatic pulmonary disease is tolerated even in patients with severe decreases in pulmonary function. PMID- 8468973 TI - Alteration of the systemic antitumor activity of melphalan by sodium cyanate in MOPC-460D myeloma-bearing BALB/c mice. AB - Sodium cyanate is a selective inhibitor of protein synthesis in a variety of mammalian tumor cells without a corresponding effect on normal tissue of the tumor-bearing animals. In the present study, we investigated the potential role of sodium cyanate in the augmentation of the antitumor activity of melphalan in MOPC-460D myeloma-bearing BALB/c mice. The simultaneous intraperitoneal injection of sodium cyanate, 250 mg/kg, and melphalan, 12 mg/kg, followed by another dose of sodium cyanate, 200 mg/kg, administered 18 hours later, resulted in a tumor growth inhibition index (TGII) of 207%. In contrast, melphalan or sodium cyanate administered separately at the same dose induced a TGII of 133% and 15%, respectively, when compared to control animals. Furthermore, a direct comparison of the volume of tumor implants in mice treated with the combination of sodium cyanate and melphalan vs. those treated with melphalan alone showed a statistically significant growth inhibition in favor of the sodium cyanate and melphalan combination on days 35, 39, and 42 from initiation of treatment. The data presented here suggest that the antitumor activity of melphalan could be increased, with moderate toxicity, by the concomitant intraperitoneal administration of sodium cyanate in BALB/c mice bearing measurable subcutaneous MOPC-460D tumor transplants. This is the first report of an increase in melphalan antitumor activity by sodium cyanate at a tumor location distant from the site of injection. PMID- 8468974 TI - Dependence of the thymidylate synthase inhibition rate on the interval after the last administration of tegafur in sigmoid colon cancer patients. AB - The thymidylate synthase (TS) inhibition rate was measured after tegafur (FT) administration (1.5 g/day, at least 10 days) in 7 sigmoid colon cancer patients. The TS inhibition rate decreased as the interval between the time of the last administration and the time of the tumor resection increased longer. This study provides basic data for considering methods of drug administration and assessment of modification, for example, by leucovorin. PMID- 8468975 TI - Relationship between age and the time of surgery and prognosis after gastrectomy for gastric cancer. AB - We did a retrospective study to assess the influence of age on the prognosis in 1,537 patients with gastric cancer and who underwent gastrectomy. The patients were classified into 7 groups by age at the time of surgery, and the relative survival rates were calculated after correcting for each patient's sex, age, and the operative calendar year, based on the life table data for the general Japanese population. The overall prognoses in patients under age 30 and over age 80 years were poor (for ages under 30 years, 30-39, 40-49, 50-59, 60-69, 70-79, and over 80 years, the 5-year survival rates were 32.1%, 55.9%, 54.8%, 54.3%, 48.6%, 50.8%, and 31.5%, respectively). The poor prognoses in the youngest patients could be attributed to a high frequency of aggressive stage of the tumor. After curative gastrectomy, although the prognoses were excellent for every category in the first and second postoperative year, patients over age 80 years had a relatively poor prognosis after the third postoperative check-up. The poor prognoses in the oldest patients were attributed to the number of deaths due to other diseases. We conclude that for the very young or old subjects, age is a significant prognostic factor for those treated by gastrectomy for gastric cancer. PMID- 8468976 TI - Primary osteosarcoma of the breast. PMID- 8468977 TI - Colorimetric chemosensitivity testing using sulforhodamine B. AB - A colorimetric chemosensitivity test was investigated using sulforhodamine B (SRB), which stains protein synthesized by cells, as an end-point marker. Four cultured cell lines, 9 human tumor xenografts serially transplanted into nude mice, and 14 fresh surgical specimens were subjected to this assay. The optimal conditions for the assay were 3-5 x 10(4) cells per well in a 96-microplate, an SRB concentration of 4%, and an incubation time of more than 10 minutes. When mitomycin C, doxorubicin, cisplatin, and 5-fluorouracil were assessed by the SRB assay, the concentration-effect curves revealed a sharp slope between plateaux at low and high concentrations, suggesting that this assay has an excellent sensitivity which can assess the effect of drugs as "all or none." Although this high sensitivity resulted in good reproducibility of the assay for cultured cell lines, the predictive rate of the SRB assay for the chemosensitivity of human tumor xenografts in vivo was limited to 63.9%. As a result, this SRB assay is thought to be useful for evaluating the chemosensitivity of cultured cells as all or none, since it can assess directly cellular protein synthesis, which is one of the most important parameters of cell renewal, with excellent sensitivity. PMID- 8468978 TI - Experimental cancer chemotherapy using a liver metastatic model of human colon cancer transplanted into the spleen of severe combined immunodeficient mice. AB - We have developed a liver metastatic model of human colon cancer using severe combined immunodeficient (SCID) mice. Liver metastases were observed in all the SCID mice on day 28 after intrasplenic injection with 5 x 10(6) dissociated tumor cells of COL-2-JCK, a human colon cancer strain serially transplanted in nude mice. When this model was applied for chemotherapeutic experiments, 5 fluorouracil (5-FU) demonstrated significant antitumor effects in preventing liver metastases, whereas the efficacy of 5-FU was limited in the currently used sc-ip chemosensitivity assay in nude mice. When the human LDH-5 isozyme was evaluated in the homogenized metastatic liver tissue of SCID mice, a good correlation was obtained between the liver tumor weights and LDH-5 isozyme, suggesting that it could be a promising quantitative indicator for metastases. This model would be useful for further studies on the treatment of liver metastases of colon cancer. PMID- 8468979 TI - Heterogeneity in early and advanced gastric carcinomas by flow cytometric DNA analysis. AB - We investigated 230 systematically sampled fresh specimens from 12 early and 26 advanced gastric cancer patients by DNA flow cytometry for heterogeneity in DNA content. Fifty-eight percent of the 12 early gastric cancers were uniformly diploid and 42% were uniformly aneuploid. Fifty-four percent of advanced cancers were uniformly diploid in superficial layers and 42% were uniformly diploid in deep layers, whereas 46% were uniformly aneuploid in superficial layers, and 50% were uniformly aneuploid and 8% were heterogeneously aneuploid and diploid in deep layers. Both diploid and aneuploid samples were obtained from 15% for advanced cancers, but ploidy heterogeneity did not occur in early cancers. Heterogeneity for DNA index (more than one aneuploid DNA index) occurred in 46% of whole thickness of advanced cancers, in 19% of superficial layers of advanced cancers, and in 8% of early cancers. We concluded that DNA ploidy determination using superficial layer specimens may be reliable in early gastric cancer but must be interpreted with care in advanced cancer. PMID- 8468980 TI - Prognostic significance of tumor-host interaction in clinical gastric cancer: relationship between DNA ploidy and dendritic cell infiltration. AB - DNA ploidy of tumor cells and the degree of infiltration of dendritic cells were determined in 93 gastric cancer tissue specimens, and the mechanisms of tumor host interaction on the prognosis were investigated. DNA ploidy patterns were grouped into low and high ploidy, and the degree of infiltration of dendritic cells (DC) was graded into marked and slight infiltration. In the low ploidy group, the 5-year survival rates in patients with marked and slight DC infiltration were 80.7% and 61.5%, respectively (P < 0.05). In the high ploidy group, however, there were no significant differences. In cases of low ploidy, the incidence of lymph node metastasis was significantly lower in the marked DC infiltration group compared with findings in the slight DC group. Thus, markedly infiltrating dendritic cells in gastric cancer tissue may lead to prolongation of survival time for patients with a carcinoma of the low ploidy profile, by preventing widespread nodal involvement. PMID- 8468981 TI - Breast conservation versus mastectomy: patient preferences in a community practice in Kentucky. AB - Recent studies have indicated a relatively low rate of breast-sparing surgery for carcinoma in the Southeastern United States. From 1987 through 1991, 289 patients from Eastern and Central Kentucky with breast carcinoma were treated by the authors. Despite being fully informed of treatment options of breast cancer, 82% of patients with stage II disease or less and no medical contraindications to breast conservation preferred mastectomy. Overall, 10% of patients underwent breast-sparing surgery, although this figure had risen to 20% by 1991. The most frequent reasons for preference of mastectomy were fear and inconvenience of radiotherapy and a perception that survival would be diminished if mastectomy was not done. PMID- 8468982 TI - Oncocytic tumors of salivary gland type: a study with emphasis on nuclear DNA ploidy. AB - We studied nine cases of oncocytic tumors of salivary gland type in order to evaluate their clinico-pathologic profiles and nuclear DNA patterns as criteria for the differential diagnosis between benign and malignant forms. The tumors were located at the parotid gland, palate, and orbit. The age of the patients ranged between 35 and 85 years and the sex ratio (F:M) was 1:0.8. Seven tumors were capsulated and had typical cytology: they were composed of polyhedrical cells with large, eosinophilic, and granular cytoplasm and dark nucleus. The remaining two tumors exhibited malignancy criteria for the oncocytic tumors: atypia, pleomorphism, and mitosis. The evaluation of the nuclear DNA content was also distinct: benign tumors had a DNA diploid pattern and the malignant neoplasms displayed a DNA aneuploid pattern. These observations point to DNA nuclear assessment as an additional criterion to discriminate neoplasms with divergent clinical behavior and prognosis. PMID- 8468983 TI - Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. AB - The relationship between status of the surgical margin and local control of soft tissue sarcoma of the extremities by preoperative radiation therapy has been assessed in 132 consecutive patients from 1974 to 1988. The 5-year actuarial local control rate was 94% for all patients; the rates were 97% and 82% for the 104 tumors with negative margins and the 28 tumors with positive margins, respectively. The local control rate was independent of the extent of the negative margin. For primary sarcomas, the local control rates were 96%, 97%, and 100%, respectively, for margins that were negative at < or = 1 mm or > 1 mm, or the specimens were negative for tumor; for positive margins the result was 83%. The overall local control rate was lower (not significant) for recurrent than for primary sarcomas: 88% vs. 94%. On the other hand, when stratifying by margin status, no difference was observed in local control results, i.e.: (1) 97% and 91% for primary and recurrent tumors with negative margins, respectively, and (2) 83% and 80% for primary and recurrent tumors with positive margins, respectively. Local control was not significantly higher in those patients who were treated by surgical resection (S), radiation (RT), and re-excision of the previous tumor bed than in those whose radiation therapy was started after the biopsy and followed by one surgical resection. For primary sarcomas that were resected with negative margins the results were: 100% of 15 patients treated by S-RT-S and 96% of 75 patients treated by RT-S. PMID- 8468985 TI - A simple technique for packing the bowel during pelvic operations. PMID- 8468984 TI - Staging of carcinoma of the esophagus and cardia: a comparison of different staging criteria. AB - The third edition [1988] of the Manual for Staging of Cancer of the American Joint Committee on Cancer (AJCC) was developed to permit finer discrimination between stages than was true of the previous edition [1983]. This study was designed to determine whether or not this goal was achieved. Pathologic staging of the specimens removed from 265 patients with carcinoma of the esophagus or cardia undergoing esophagogastrectomy between 1970 and 1988 was performed according to criteria published in the second and third editions and their survival data compared. The new staging criteria of the AJCC provides no better discrimination of stages according to survival than was true of the earlier version, the 5-year survival of stage IIA patients being similar to that of stage I patients (37.5 +/- 6.7% vs. 50.8 +/- 17.7%), and the survival of stage IIB patients being similar to that of stage III patients (16.2 +/- 8.1% vs. 13.6 +/- 3.7%). However, depth of wall penetration and extent of lymph node involvement were reliable independent predictors of survival. We propose a modified version of the Skinner WNM staging plan that provides a modest increase in staging fragmentation. PMID- 8468986 TI - Preliminary experience with a modified Tenckhoff catheter for intraperitoneal chemotherapy. AB - This study reports our preliminary experience with a modified Tenckhoff catheter for intraperitoneal chemotherapy, primarily designed to be larger, longer, and have more perfusion holes. There were 137 catheters implanted in 125 ovarian cancer patients from June 1988 to December 1990, among which 116 were actually used for intraperitoneal chemotherapy. A total of 559 cycles of intraperitoneal chemotherapy was given with a range of 1 to 16 uses per catheter. There were seven infections (6.0%), four inflow obstructions (3.4%), three bowel perforations (2.6%), and one leakage (0.8%). Among patients with catheter infection, three had delayed bowel perforation. Although the incidence of inflow obstruction was reduced from 5.5 to 3.4%, the improvement did not reach statistical significance. The frequency of delayed bowel perforation and infection were similar to the literature experience of other catheters. An unused catheter should be removed to avoid this serious complication. Further study is needed to evaluate fully the performance of this catheter system. PMID- 8468987 TI - Selective use of drains in thyroid surgery. AB - In the past, it was generally advised that every patient undergoing thyroid surgery have a drain placed because of the fear of post-operative hematoma. In the past 9 years, we have performed 400 thyroidectomies. For the first 6 years, we drained the operative site in most of thyroid procedures. However, it was apparent from our experience that drains had very little effect on the prevention of post-operative hematoma or of seroma. As a matter of fact, all four patients who required re-exploration in our initial series had drains in place. As a result of this experience over the past 3 years, during which time we have performed 150 thyroidectomies, we have used drains selectively. The indications for draining the thyroid bed have been the presence of a large dead space, operation for a large substernal goiter, and subtotal thyroidectomy for either large, multinodular goiter or for Graves' disease. Thus, among 150 recent thyroidectomies, we have drained only 35, and avoided drains in 115 patients. Though this is not a prospective study, we found no difference in the overall outcome whether drains were employed or not. Most patients who had no drains were ready for discharge within 24-48 hours of surgery. Since it may be difficult to perform a randomized prospective trial examining the use of drains in thyroid surgery, we propose that drains should be utilized only selectively for thyroid surgery. PMID- 8468988 TI - Preoperative duplex venous imaging in the assessment of patients with venous access. AB - Occult or clinically apparent central venous thrombosis frequently complicates central venous catheter placement in patients requiring long-term vascular access. Thirty-three patients, aged 12-83 years, underwent duplex scanning of the internal jugular, axillary, and brachial veins prior to placement of long-term venous access catheters. Twenty-seven patients underwent duplex scanning because of a prior history of either long-term or short-term central venous access. Of 12 patients with a history of long-term central venous access, without complications, 42% (5/12) had an abnormal duplex scan demonstrating thrombosis. Duplex scans on 15 patients having complications associated with central venous access demonstrated thrombosis of one or more of the central veins, 46% (7/15). Five patients who underwent duplex scanning without a history of a previous central venous catheter or other indication were found to have normal central veins. In 13 patients found to have thrombosis or obstruction by duplex scan, the surgeon was directed to successful venous access in all cases. Normal findings were very helpful in confirming that the venous system was normal in selected patients. In approximately 40% of patients with a history of venous access, catheters were found to have evidence of thrombosis of one or more of the central veins. In 13 patients found to have thrombosis or obstruction by duplex scan, the surgeon was directed to a successful site for venous access in all cases. PMID- 8468989 TI - Adjuvant regional isolated perfusion with melphalan for patients with Clark V melanoma of the extremities. AB - From 1978 to 1990, 32 patients with Clark V melanoma were treated by wide excision of the primary and adjuvant regional isolated perfusion with melphalan. M.D. Anderson stage of disease was stage I in 22 and stage IIIb in 10 patients. Five-year survival rates were 58% and 27%, respectively. Seven patients developed a recurrence in the perfused limb [stage I, 2, stage IIIb, 5 patients (P = 0.03)], and 4 of 17 patients developed regional lymph node metastases. Of the well-known prognostic variables, only ulceration of the primary tumor significantly influenced survival (P = 0.03). We did not see any improvement in survival rates compared with literature data on nonperfused patients. In the absence of data on locoregional recurrence rates in nonperfused Clark V melanoma patients, we cannot say whether adjuvant perfusion diminished this risk. Therefore, the results of the prospective randomized EORTC/WHO trial in primary high-risk extremity melanoma have to be awaited. PMID- 8468990 TI - Intraperitoneal cisplatin with sodium thiosulfate protection in rats with intestinal anastomoses. AB - Intraperitoneal (IP) cisplatin administered at the time of intraabdominal malignancies such as gastric cancer may prevent or delay intraabdominal recurrence. Perioperative IP cisplatin raises concerns regarding systemic toxicity and retardation of wound healing. Systemic cisplatin toxicity may be reduced by administering its antidote, sodium thiosulfate (STS). A preclinical study of IP cisplatin in rats undergoing a small intestinal anastomosis was carried out. All animals that had received only cisplatin died in the postoperative period as a consequence of cisplatin toxicity. Tensile strength of the intestinal anastomoses was determined on the tenth postoperative day in the surviving animals. Animals that had received intravenous (IV) cisplatin with STS had significantly lower tensile strengths than both those receiving IP cisplatin with STS and STS alone. This study demonstrates the safety of perioperative cisplatin with STS protection by the avoidance of systemic toxicity and minimizing the cisplatin-related retardation of wound healing. PMID- 8468991 TI - Complete disappearance of a leiomyosarcoma of the lower extremity following preoperative hyperthermia and intra-arterial doxorubicin. AB - Leiomyosarcoma of the extremities is an unusual tumor. Herein we report a unique and what we believe is the first case of a patient in whom there was complete disappearance of such a tumor following regional hyperthermia and chemotherapy. PMID- 8468992 TI - Superior function of a bicuspid over a monocuspid patch for reconstruction of a hypoplastic pulmonary root in pigs. AB - In an experimental study in pigs, the function of monocuspid and bicuspid patches was compared to improve surgical reconstruction of a hypoplastic pulmonary root. Segments from glutaraldehyde-treated porcine aortic roots served as monocuspid and bicuspid patches. Their leaflets and commissures were marked with radiopaque metal clips. Marker movements were recorded at 100 frames/sec. Quantification of pulmonary insufficiency, right ventricular stroke volume, as well as pressures in the right ventricle, pulmonary artery, and aorta was performed before and after patch plasty. The cyclic motion of the leaflets showed a three-phase pattern in monocuspid and bicuspid patches: (1) a rapid opening motion with a significantly longer distance to be covered in monocuspid patches (7.5 mm in monocuspid versus 4.9 mm in bicuspid patches); (2) a slow closing motion that was significantly greater in monocuspid patches (31.5% of maximal displacement in monocuspid versus 18.2% and 23.8% in bicuspid patches); (3) a similar rapid closure motion in both types of patches. The commissural expansion was less than 6% for monocuspid and bicuspid patches and began 10 to 20 msec before valve opening. Considerable irregularities in the movement of the different leaflet markers, especially in monocuspid patches, indicated leaflet buckling as a result of redundant leaflet tissue. There was a significant pulmonary regurgitant fraction only in monocuspid patches (19% in monocuspid versus 7% in bicuspid patches) that occurred during early diastole. No pressure gradients were observed across either type of patch. In monocuspid patches, a greater leaflet displacement during rapid closure was correlated with an increased pulmonary insufficiency (r = 0.8875). In conclusion, the function of a bicuspid patch is superior to that of a monocuspid patch for repair of a hypoplastic pulmonary root and allows the construction of a competent and stenosis-free valve mechanism. PMID- 8468993 TI - Intraventricular repair for Taussig-Bing anomaly. AB - Among 41 patients with Taussig-Bing anomaly who underwent intracardiac repair, 10 patients were treated by intraventricular rerouting repair. The ages at operation ranged form 1 month to 8 years (average 2 years 3 months). Primary repair was done in four (average age 2 years 7 months), and repair was done after pulmonary artery banding in six patients (average age 2 years 2 months). The relationship of the great arteries was side by side in nine patients and oblique in one. After extensive resection of the infundibular septum, a distance of 8 to 18 mm from the tricuspid ring or chordae to the pulmonary valve was obtained (24% to 71% of total circumference for the subaortic route). The subaortic route was created to obtain an internal diameter at least equal to that of the aortic route. Tricuspid chordal or papillary muscle reattachment was performed in two patients. There were no early or late deaths. Follow-up ranged from 1 year 4 months to 22 years 3 months (average 5 years 8 months), and reoperation was required in one patient for residual pulmonary stenosis. The intraoperative pressure gradient between the left ventricle and aorta was 0 to 24 mm Hg (average 10.3 mm Hg), and postoperative study showed the gradients to be less than 19 mm Hg (n = 8). The age at operation, left ventricular-aortic pressure gradient, and postoperative tricuspid regurgitation were not significantly affected by the presence of severe hypertrophy of the infundibular septum (n = 4). These results indicate that intraventricular rerouting may be feasible in most patients who have the Taussig Bing anomaly with side-by-side or similar relationships of the great arteries, and the age and conal anatomic variations do not appear to be significant limiting factors. PMID- 8468994 TI - A computer simulation of the plasma leakage through a vascular prosthesis made of expanded polytetrafluoroethylene. AB - We explored the blood-retaining mechanism of a vascular prosthesis made of expanded polytetrafluoroethylene through analysis of its structure and physicochemical properties. Plasma leakage through this vascular prosthesis was simulated by computer to explore its etiology. These examinations disclosed that leakage is dependent upon the inner pressure and the density of fibers. In other words, the study revealed that the mean distance between fibers constituting the wall of the expanded polytetrafluoroethylene vascular prosthesis is increased by tension (that is, inner pressure), resulting in an increased probability of leakage. It was additionally found that a thin membrane is formed on the polytetrafluoroethylene surface if blood in contact with the surface is dried. This membrane was found to reduce the water-repelling property of polytetrafluoroethylene and to make it impossible to preserve the inter-fiber liquid surface, thus causing leakage through the expanded polytetrafluoroethylene vascular prosthesis. PMID- 8468995 TI - The effect of coronary reoperation on the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries. AB - Does coronary artery reoperation improve the survival of patients with stenoses in saphenous vein bypass grafts to coronary arteries? To examine this question, we retrospectively reviewed 1117 patients who had coronary bypass grafting and then underwent a postoperative coronary angiogram that showed a stenosis (> or = 20%) of at least one vein graft. Reoperation within 1 month of the postoperative angiogram was performed for 394 patients (REOP group) whereas 723 patients (MED group) received initial medical treatment (no reoperation or percutaneous transluminal coronary angioplasty within 1 year). Compared with the MED group, patients in the REOP group were older, more symptomatic, more likely to have left main stenosis, and had fewer patent bypass grafts (all p < 0.001). In-hospital mortality for the REOP group was 4.3%. Mean postangiogram follow-up of the entire group was 73 months. On the basis of the interval between the primary operation and the postoperative angiogram, patients were designated as having early (< 5 years) or late (> or = 5 years) saphenous vein graft stenosis. Univariate and multivariate analyses were used to identify factors influencing the survival of these subgroups. Reoperation was not identified as a variable improving the survival of patients with early vein graft stenoses. For patients with late vein graft stenoses, moderate or severe impairment of left ventricular function (p < 0.0001), advanced age (p < 0.0001), triple-vessel or left main stenosis (p = 0.0011), and stenosis in a vein graft to the left anterior descending artery (p = 0.0019) decreased survival, whereas reoperation improved survival (p = 0.0007). The improvement in survival with reoperation was particularly strong for patients with a stenotic vein graft to the left anterior descending artery. For that subset, survival was 84% and 74% for the REOP group versus 76% and 53% for the MED group at 2 and 4 years after catheterization, respectively (p = 0.004). For patients with stenotic vein grafts to the right coronary artery or circumflex coronary artery (or both), survival was 92% and 87% for the REOP group versus 89% and 78% for the MED group at 2 and 4 years after catheterization, respectively (p = 0.13). Even for patients with class I or II symptoms, reoperation prolonged survival (p = 0.002 with multivariate testing). Reoperation improves the survival of patients with late vein graft stenoses, particularly those with stenotic grafts to the left anterior descending coronary artery. PMID- 8468996 TI - Left ventricular function in experimental mitral regurgitation with intact chordae tendineae. AB - Left ventricular function in mitral regurgitation has typically been studied in models that either sever the chordae tendineae or create a ventriculoatrial shunt. These methods may have adverse effects on left ventricular function independent of the regurgitant lesion. An animal model of chronic mitral regurgitation was therefore developed that both preserves annuloventricular continuity and avoids the use of external shunts. A circular 0.16 to 0.24 mm/kg defect was created in the anterior mitral valve leaflet of weanling sheep under direct vision with the aid of cardiopulmonary bypass. Six animals were studied preoperatively and immediately postoperatively (acute regurgitation group), and 20 animals were studied 8.1 +/- 0.2 (mean +/- one standard deviation) months postoperatively (chronic regurgitation group). Animals with chronic mitral regurgitation were compared with an age- and weight-matched control group that was not operated on (n = 7). Volumetric data and ejection fraction were derived from digitalized cineangiographic images. Maximal elastance was calculated from pressure-volume loops obtained from the simultaneous recording of left ventricular pressure by micromanometer-tipped left ventricular catheters, and volumes were obtained from digitalized images of epicardial echocardiographic recordings. Mitral valve perforation resulted in 3+ to 4+ mitral regurgitation and a calculated regurgitant fraction of 37% +/- 7% (mean +/- one standard deviation). Acute mitral regurgitation was associated with an increase in left ventricular end-diastolic volume from 110 +/- 17 to 121 +/- 23 ml (p < or = 0.05) and no change in end-systolic volume. These changes were associated with an increase in fractional shortening, from 29% +/- 11% to 40% +/- 10% (p < or = 0.05), and an increase in velocity of circumferential shortening, from 1.5 +/- 0.7 to 2.9 +/- 0.7 circ/sec (p < or = 0.05). However, there was no change in maximal elastance, a load-independent index of left ventricular function. Conversely, animals with chronic mitral regurgitation exhibited an elevated end diastolic volume (202 +/- 32 versus 145 +/- 34, p < or = 0.05), an elevated end systolic volume (104 +/- 17 versus 63 +/- 20 ml, p < or = 0.05), and a reduced ejection fraction (48% +/- 6% versus 57% +/- 9%, p < or = 0.05) compared with controls.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8468997 TI - Long-term results of mitral commissurotomy. AB - Between January 1968 and December 1989, 280 patients underwent conservative surgical treatment for pure mitral stenosis. Closed commissurotomy was utilized in 134 patients, with a mean age of 38 +/- 11 years and a mean valve area of 1.0 +/- 0.29 cm2. Open commissurotomy was performed in 146 older patients (mean age 44 +/- 11 years) with a mean valve area of 0.9 +/- 0.3 cm2. The perioperative mortality was 3% in closed procedures and 3.4% in open procedures. Surviving patients were evaluated by questionnaires or phone interviews, and 129 patients were examined by two-dimensional echocardiography with the purpose of analyzing long-term results. Follow-up was 95% complete (Grunkemeier-Starr method), with a median of 18 years in patients with closed commissurotomy and 6.6 years in patients with open commissurotomy. The actuarial survival at 21 years was 60.8% (70% confidence limits 55% to 66%) in patients having closed commissurotomies and 60.6% (70% confidence limits 49% to 71%) at 22 years in patients having open commissurotomies. The "effective palliation" rate, defined by clinical and echocardiographic criteria, was 47% at 15 years and 15% at 20 years. We conclude that mitral commissurotomy is the procedure of choice in pure mitral valve stenosis and should be applied early. When performed in patients aged less than 40 years, a 78% (70% confidence limits 72% to 84%) survival at 18 years and 67% "effective palliation" at 15 years were observed. The closed valvotomy results of our study support the present trend toward use of percutaneous balloon valvotomy. PMID- 8468998 TI - Annuloplasty with flexible or rigid ring does not alter left ventricular systolic performance, energetics, or ventricular-arterial coupling in conscious, closed chest dogs. AB - Eighteen dogs were randomly chosen to undergo mitral annuloplasty with either a Carpentier-Edwards rigid ring (n = 6 in each group) or a Duran-Medtronic flexible ring or to undergo a sham procedure with an operation, but no ring. Tantalum markers were inserted to measure left ventricular volume and geometry. After 1 and 6 weeks, biplane videofluoroscopic images were obtained during steady-state conditions and during vena caval occlusion. Global and regional systolic function was assessed with load-insensitive indexes. Comparison of all three groups and both times (1 and 6 weeks) showed no significant differences among the three groups in global or regional (basal, equatorial, and apical) left ventricular systolic performance. Furthermore, neither type of annuloplasty ring significantly affected left ventricular pump efficiency, ventricular-arterial coupling ratio, or systolic circumferential contraction and rotation of the basal left ventricular sites. PMID- 8468999 TI - A clinical trial of University of Wisconsin solution for pulmonary preservation. AB - Suboptimal pulmonary preservation with modified Euro-Collins solution (9/90 to 4/91) prompted us to change to University of Wisconsin solution (4/91 to 4/92). Between September 1990 and April 1992, 94 patients received 100 pulmonary allografts (13 heart-lungs, 45 double lungs, 42 single lungs) that were flushed and preserved with either Euro-Collins (n = 30) or University of Wisconsin (n = 70) solution. Selection of donors and procurement and storage of donor lungs were identical. Bilateral single lung transplantation was performed more often in the University of Wisconsin group and resulted in a significantly longer graft ischemic time (University of Wisconsin group; 303 +/- 62 minutes; Euro-Collins group; 260 +/- 62 minutes; p = 0.007, t test). The use of cardiopulmonary bypass was not statistically significantly different. Preservation injury identified by the radiograph on day 1 was more severe (p = 0.036; Mann-Whitney U test) in the Euro-Collins group than in the University of Wisconsin group. In double lung and heart-lung recipients gas exchange of the allografts was evaluated by the arterial/alveolar oxygen tension ratios at nine intervals during the first 72 hours. The mean arterial/alveolar oxygen tension ratio was 0.62 +/- 0.26 in the University of Wisconsin group and 0.46 +/- 0.23 in the Euro-Collins group, but this difference did not reach significance (p = 0.119, analysis of variance). Despite the longer ischemic time, pulmonary preservation achieved by University of Wisconsin solution appears to be comparable with that achieved by Euro-Collins solution. PMID- 8469000 TI - A comparison of intracellular solutions for donor heart preservation. AB - Numerous solutions have been advocated for the preservation of donor hearts, and there has been much interest in universal and intracellular preservation solutions. This study compared the effects of Euro-Collins, University of Wisconsin, and Bretschneider's solutions with the use of an in vitro human right atrial muscle preparation to assess recovery of function after a 24-hour period of simulated cardiac arrest. There were no statistically significant differences among groups in length, weight, cross-sectional area, initial developed force, or resting force of muscles, including those muscles that were contracted in Krebs Henseleit solution and served as a control. After the 24-hour arrest period at either 4 degrees or 12 degrees C, the solution was changed back to Krebs henseleit at 34 degrees C and recovery was assessed over 30 minutes. At 30 minutes, developed forces for muscles that were cooled to 4 degree C were 58.9%, 76.6%, and 60.7% of the control for Euro-Collins, University of Wisconsin, and Bretschneider's solutions, respectively (p = not significant). For those cooled to 12 degrees C, developed forces were 9.5%, 30.5%, and 95.6% of the control for Euro-Collins, University of Wisconsin, and Bretschneider's solutions (p = 0.0001). Bretscheider's solution resulted in greatly improved recovery compared with both Euro-Collins and University of Wisconsin solutions (p = 0.005), and University of Wisconsin solution was better than Euro-Collins solution (p = 0.02). Recovery of developed force was affected by temperature for Euro-Collins and University of Wisconsin solutions (p = 0.005 and p = 0.001, respectively) but not for Bretschneider's solution. Resting force was elevated in muscles that were cooled in both Euro-Collins and University of Wisconsin solutions at 12 degrees C compared with almost normal values for Bretschneider's solution at either temperature (p = 0.07). Bretschneider's solution has a very high buffering capacity, which may be beneficial for long-term preservation. In conclusion, Bretschneider's solution resulted in the best recovery of human atrial myocardial function after a 24-hour preservation period compared with Euro-Collins and University of Wisconsin solutions and should be considered for use in donor heart transportation. The variability in quality of preservation at different temperatures with either Euro-Collins or University of Wisconsin solution make them less desirable as preservation solutions because uniform temperatures are seldom obtained during donor heart transplantation. PMID- 8469001 TI - The sensitivity of transbronchial biopsy for the diagnosis of acute lung rejection. AB - Transbronchial biopsy has become the procedure of choice for the diagnosis of acute lung rejection after transplantation, but the sensitivity of the technique in this setting remains unknown. In this study, 14 mongrel dogs underwent left lung transplantation, after which triple-drug immunosuppression was given for 5 days and then all immunosuppression was stopped. All animals had clear chest radiographs at this time. Transbronchial biopsy was performed in nine lung regions (two to six pieces of lung tissue were obtained per region, with a mean of 4.3 pieces per region) before the animals were killed 2 to 4 days later, at which time varying degrees of rejection had occurred. Rejection was graded histologically on a scale of 0 to 3 (0 = no rejection, 1 = mild rejection, 2 = moderate rejection, 3 = severe rejection) in each piece of lung tissue obtained at transbronchial biopsy. After the dogs were put to death, the true state of lung rejection was determined by histologic examination of the entire lung. We calculated the sensitivity of transbronchial biopsy with 95% confidence intervals. Five pieces of lung tissue were needed to yield a sensitivity of 92% (82%, 100%) to identify mild rejection in the entire lung with transbronchial biopsy. Three pieces of lung tissue were needed to yield a sensitivity of 92% (84%, 100%) to identify the presence of moderate to severe rejection in the entire lung (that is, rejection that requires pulse therapy) on transbronchial biopsy. These results indicate that three to five pieces of lung tissue that are suitable for diagnostic purposes obtained at transbronchial biopsy are adequate for the diagnosis of acute pulmonary rejection after lung transplantation. PMID- 8469002 TI - Determinants of myocardial oxygen consumption in fibrillating dog hearts. Comparison between normothermia and hypothermia. AB - The purpose of the present study was to elucidate the mechanism of the difference in myocardial oxygen consumption between heating and fibrillating states during normothermia and hypothermia. In five isolated cross-circulated dog hearts, we measured left ventricular pressure at several ventricular volumes and myocardial oxygen consumption at V0 and V100, at which peak isovolumic pressures were zero and approximately 100 mm Hg, respectively, in beating and fibrillating states during normothermia and hypothermia (29 degrees C). As a measure of the total mechanical energy at V100, we obtained pressure-volume area in the beating state and equivalent pressure-volume area for fibrillation. We calculated equivalent heart rate as an estimate of the contraction frequency of individual myocytes in a fibrillating ventricle from myocardial oxygen consumption at V0 in the beating and fibrillating states. During normothermia, myocardial oxygen consumption per minute at V0 and V100 and myocardial oxygen consumption for mechanical purposes at V100 (myocardial oxygen consumption at V100-myocardial oxygen consumption at V0) were significantly higher during fibrillation than in the beating state. Equivalent pressure-volume area during fibrillation and pressure-volume area in the beating state at V100 were comparable, whereas equivalent heart rate during fibrillation was significantly higher than heart rate in the beating state. During hypothermia, myocardial oxygen consumption was comparable between beating and fibrillating states at V0, although myocardial oxygen consumption at V100 was slightly lower during fibrillation than in the beating state. Myocardial oxygen consumption for mechanical purposes during fibrillation was half of that in the beating state. Equivalent pressure-volume area was significantly smaller than pressure-volume area, whereas equivalent heart rate and heart rate were comparable. We conclude that during normothermia, higher myocardial oxygen consumption during fibrillation than in the beating state at V0 and V100 is attributable to the higher contraction frequency. During hypothermia the comparable myocardial oxygen consumption values at V0 are attributable to the comparable contraction frequencies, whereas slightly lower myocardial oxygen consumption during fibrillation at V100 is ascribed to the lower total mechanical energy. PMID- 8469003 TI - Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury? AB - After crystalloid cardioplegic arrest, cardiac-derived thromboxane A2 may be an important initiating mediator of no-reflow and hemodynamic deterioration during reperfusion because of its potent vasoactive properties. Although previous studies have already documented the increased release of cardiac thromboxane A2 after ischemia, none have studied the effects of cardiac thromboxane A2 on hemodynamics. We therefore tested the ability of cardiac thromboxane A2 to mediate deterioration of coronary flow and functional recovery during reperfusion after global ischemia. Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548. In eight of 15 hearts in each group, preischemic and postischemic aortic flow, coronary flow, cardiac output, heart rate, and stroke work were determined. In the remaining seven hearts in each group, preischemic and postischemic coronary effluent levels of the stable hydrolysis product of thromboxane A2 and thromboxane B2 were determined with radioimmunoassay through the use of nonrecirculating perfusate. At the completion of the experiment, water content was determined by wet weight/dry weight calculations. In a separate group (n = 7) preischemic myocardial water content was determined. Within the group protected by cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly decreased (p < 0.05) compared with preischemic values (aortic flow, 50.8 +/- 2.7 versus 29.4 +/- 3.3 ml/min; coronary flow, 13.2 +/- 1.3 versus 8.5 +/- 1.3 ml/min; cardiac output, 64.0 +/- 3.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.5 +/- 0.7 versus 7.1 +/- 0.8 cm H2O.ml). In relation to the group with cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly greater (p < 0.05) in the group with the receptor antagonist (aortic flow: 49.5 +/- 2.4 versus 29.4 +/- 3.3 ml/min; coronary flow; 12.4 +/- 1.2 versus 8.5 +/- 1.3 ml/min; cardiac output, 62.0 +/- 2.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.6 +/- 0.8 versus 7.1 +/- 0.8 cm H2O.ml). Overall, postischemic coronary effluent thromboxane B2 levels were greater than preischemic values (105.6 +/- 12.4 versus 69.6 +/- 9.8, p < 0.05) and treatment with the receptor antagonist did not significantly affect postischemic thromboxane B2 levels (92.0 +/- 7.3 versus 82.3 +/- 15.5, p = not significant). Neither ischemia nor treatment with the receptor antagonist significantly affected heart rate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8469004 TI - Acute isovolemic hemodilution and blood transfusion. Effects on regional function and metabolism in myocardium with compromised coronary blood flow. AB - The use of isovolemic hemodilution to prevent adverse side effects of homologous blood transfusions has increased. The lowest level of hemoglobin that can be tolerated without regional myocardial dysfunction, however, had not been precisely defined for left ventricular myocardium with compromised coronary blood flow. This level was determined in our study in 19 dogs with critical stenosis of the left anterior descending coronary artery during graded isovolemic hemodilution. Regional function was assessed by sonomicrometry in the territory supplied by the left anterior descending coronary artery, as well as in two noncompromised left ventricular areas; oxygen extraction and consumption in the left anterior descending coronary artery region were assessed by analysis of anterior descending coronary venous oxygen saturation. The median lowest level of hemoglobin tolerated without contractile dysfunction of the territory supplied by the left anterior descending artery was 7.5 gm/dl, with lower and upper quartiles of 6 and 9 gm/dl. In addition to a marked increase in cardiac output and transstenotic left anterior descending flow, global cardiac and regional myocardial functions were unchanged at a hemoglobin level of 7.5 gm/dl, as compared with a control level of hemoglobin of 12.0 +/- 0.4 gm/dl. At a mean level of hemoglobin of 6.0 +/- 0.4 gm/dl, marked contractile dysfunction developed in the left anterior descending region: Systolic shortening decreased from 24.2% +/- 2.1% to 17.9% +/- 1.9% (p < 0.01); postsystolic shortening increased from 4.0% +/- 3.0% to 12.2% +/- 3.8% (p < 0.01); and in the left anterior descending region, oxygen consumption decreased. The increase of arterial level of hemoglobin by only 1.9 +/- 0.2 gm/dl restored contractile function in the left anterior descending region, regional oxygen consumption, and oxygen extraction across the left anterior descending region. Moderate isovolemic hemodilution is relatively well tolerated in left ventricular myocardium with compromised coronary blood flow, and hemodilution regional contractile dysfunction induced by hemodilution is reversible by minimal blood transfusion. PMID- 8469005 TI - Relative risk of aortic and femoral insertion of intraaortic balloon pump after coronary artery bypass grafting procedures. AB - We compared the preoperative, operative, and postoperative characteristics of patients who required balloon pumps after coronary artery bypass graft procedures to determine the relative risks of femoral and aortic insertion. The balloon pump was inserted into the ascending aorta when femoral insertion was not possible because of occlusive disease or small femoral arteries. Femoral insertion was performed in 81 patients and aortic insertion in 42 patients. Patients with aortic insertion were more likely to be small and female (p < 0.05) and were more likely to have carotid bruits and a history of strokes or transient ischemic attacks (p < 0.05). Death was more common in the patients with aortic insertion (18/42, 42.9%) than in those with femoral insertion (19/81, 23.4%) (p < 0.05), as calculated with single regression analysis. Route of insertion was not a predictor of operative death, according to multiple regression analysis. Leg complications were more common in patients with femoral artery insertion (23/81, 28.4%) than in those with aortic insertion (0/42, 0.0%) (p < 0.05). No sternal complications occurred in either group. New neurologic abnormalities were not significantly different between the patients with aortic and femoral insertion. Aortic insertion is a safe alternative to femoral insertion of intraaortic balloon pumps and is associated with fewer leg complications in small or diseased iliac and femoral arteries. The greater mortality rate with aortic insertion is related to greater comorbidity rate in these patients. PMID- 8469006 TI - Anatomic lobectomy of the lung by means of thoracoscopy. An experimental study. AB - We conducted this study in an attempt to investigate whether anatomic lobectomy can be performed through a thoracoscope. Twelve lower (seven left and five right) and six left upper lobectomies were done in 17 pigs weighing 60 to 90 kg. With the use of general anesthesia and one-lung ventilation, a thoracoscope and operating instruments were inserted through four or five trocars. First, the incomplete fissure was bluntly dissected with specially designed cotton-tipped dissectors and divided by an electrocautery spatula or sapphire contact-tip neodymium: yttrium aluminum garnet laser probe. The pulmonary artery and its branches were similarly dissected. Two ligatures were passed around the vessels by endoscopic right-angle clamps and tied by means of an extracorporeal tying technique. The vessels were clipped and divided. In two animals, a hidden branch of the pulmonary artery was inadvertently cut. Bleeding was readily controlled with the dissector until metal clips could be applied. The bronchus was similarly dissected and divided and the proximal stump was closed with sutures. The pulmonary vein was dissected bluntly by the same technique and divided. The excised lobe was placed in a plastic bag and pulled out through one of the trocar holes after the hole had been enlarged to 3 cm. Blood loss was minimal. In conclusion, anatomic lobectomy of the lung by means of thoracoscopy was feasible in the pig. PMID- 8469007 TI - The use of "nonanatomic" pulmonary resection in infants with extensive congenital adenomatoid malformation of the lung. AB - In three infants with extensive congenital adenomatoid malformation of the lung, a method of nonanatomic pulmonary resection permitted preservation of small superiorly positioned pulmonary remnants. These remnants then demonstrated a surprising capacity for expansion, growth, and function during follow-up periods of 5 years, 9 months; 7 years, 6 months; and 19 years. Thus far, this small experience indicates that this method of management does not appear to entail greater short- or long-term risks than the alternative procedure of pneumonectomy. PMID- 8469008 TI - Lung volumes, mechanics, and perfusion after pulmonary resection in infancy. AB - Partial pulmonary resection in early childhood is well tolerated. Although long term outcome has been described in several follow-up studies, almost no information is available on postoperative lung perfusion. We studied 14 patients 3 to 20 years (mean, 11.6 years) after they underwent partial pulmonary resection at 1 week to 30 months of age (mean, 6.8 months). We examined development, pulmonary function, endurance, radiographs and ventilation-perfusion scans. We used predicted pulmonary function test values, which were corrected for the relative amount of lung removed and called predicted-corrected values. We hypothesized that the remaining lung would have altered ventilation-perfusion characteristics. We found no abnormalities in the patients' physical development. Most children had abnormal regional ventilation, but normal equilibration occurred; five patients had gas retention; all had decreased perfusion to the area of resection; nine patients showed ventilation-perfusion mismatch characterized by dead-space ventilation. Lung volumes were within the predicted range in 12 patients. Residual volume and functional residual capacity were larger than predicted-corrected values in most patients but residual volume in relation to total lung capacity was at or below normal in 6 of 11 and did not correlate with the amount of lung removed. Most patients had prolonged expiratory flows. We conclude that lung resection in early childhood leads to good functional recovery. However, decreased expiratory flows, regional ventilation abnormalities, and decreased perfusion suggest dysplastic parenchyma and vascular bed in the area of resection. PMID- 8469009 TI - Survival of patients with carcinoma of the esophagus treated with combined modality therapy. AB - Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years. PMID- 8469010 TI - Selective pulmonary vasodilatation with inhaled nitric oxide. PMID- 8469011 TI - Reply to invited letter concerning: assessment of myocardial ultrastructure after retrograde infusion of cardioplegic solution (J Thorac Cardiovasc Surg 1992; 104:1745-6) PMID- 8469012 TI - Blunt injury of the innominate artery: use of a vascular pericardial flap. PMID- 8469013 TI - Treatment of a patient with factor IX deficiency (hemophilia B) with coronary bypass surgery. PMID- 8469014 TI - Isolated unilateral pulmonary artery agenesis. PMID- 8469015 TI - Static and dynamic models of interdisease competition: past and projected mortality from amyotrophic lateral sclerosis and multiple sclerosis. AB - Longitudinal Gompertzian analysis is an effective method for determining both the pure probability of death for a given condition and the size of inherently susceptible subpopulations [1]. Gompertzian analysis has been used in this study to provide the parameters necessary to construct a stationary population lifetable (static model) of mortality for amyotrophic lateral sclerosis (ALS) and for multiple sclerosis (MS). The static model demonstrates the relative effect of changing general mortality upon the mortality from each specific disease in a situation where interdisease competition is continuously changing. In order to represent mortality in a real population more closely (where age structure is not the result of mortality rates alone) a dynamic model was constructed for both conditions using the age distributions of the population of England and Wales. The quality of the model was verified by comparison of estimated mortality with historical data from the last three decades. The dynamic model has then been used to estimate mortality from each condition over the next three decades on the basis of population projections made by the Central Statistical Office [2], assuming no major change in the factors which lead to either condition. This analysis demonstrates both the theoretical applicability and practical capabilities of Gompertz-derived mortality models for analysing changing mortality patterns. PMID- 8469016 TI - Accumulation of cardiac lipofuscin in crab-eating monkeys (Macaca fasicularis): the same rate of lipofuscin accumulation in several species of primates. AB - Previously, we have reported that the aging process begins at sexual maturation (Nakano, M. et al., Mech. Ageing Dev., 52 (1990) 93-106). In this paper, we reported the cardiac lipofuscin accumulation of crab-eating monkeys. The first appearance of cardiac lipofuscin was around sexual maturation, and the rate of accumulation in crab-eating monkey was 0.45. Several primates which have different life spans show the same rate of lipofuscin accumulation in the life stage. Namely, even in a different life span, the amount of lipofuscin accumulation in a given period of life such as puberty, middle age, old age was the same. From these results, it is suggested that the amount of lipofuscin accumulation is the same in the life span of primates having different life spans. PMID- 8469017 TI - Aging and mortality: manifestations of increasing informational entropy of the genome? AB - Information theory has provided insight to the means by which organisms maintain life against the inevitable influence of the second law of thermodynamics. The low entropy content of genetic information is used to harness the energy that an organism in an open system must utilize to maintain its low entropy and life. Redundancy lowers informational entropy, enhances meaning and promotes complexity. The genome is characterized by large quantities of 'redundant' DNA. Longitudinal Gompertzian analysis has shown that 'the rate of loss of vitality' (from the Strehler-Mildvan modification of the Gompertz model of aging and mortality) has remained constant for general and disease-specific mortality. Applying the concepts of information theory to aging and mortality suggests that 'the rate of loss of vitality' may be synonymous with the rate of degradation of redundant genetic information (or alternatively, the rate of increase in informational entropy of the genome). This interpretation is consistent with the hypothesis that genetic instability of repeated DNA sequences may be fundamentally related to the process of aging. Consequently, there may be no specific aging or 'death' genes per se, but rather aging and mortality are the inevitable natural consequence of increasing informational entropy (decreasing redundancy) contained within the genome. PMID- 8469018 TI - Age-related changes in homeostasis of inorganic sulfate in male F-344 rats. AB - Advanced age is associated with a decline in renal function including decreased glomerular filtration rate, renal blood flow and renal tubular secretion. Endogenous inorganic sulfate homeostasis is maintained by concentration-dependent active renal reabsorption in the proximal tubule. The purpose of this study was to determine the effects of advanced age on: (1) the renal mechanisms for conserving endogenous inorganic sulfate and (2) the turnover of inorganic sulfate. Awake, male Fischer 344 rats age 4-5 months and 22-23 months received i.v. acetaminophen, 300 mg/kg, followed 2 h later by i.v. sodium sulfate, 2 mmol/kg, to lower and raise, respectively, plasma inorganic sulfate in order to measure the renal clearance of this anion from plasma at sub- and supraphysiologic concentration ranges. Another group of old and young male F-344 rats received a tracer injection of [35S]sodium sulfate to determine the effect of aging on the turnover of the endogenous inorganic sulfate pool. There was no statistically significant effect of advanced age on baseline plasma sulfate concentration or on the renal clearance of inorganic sulfate from plasma. The baseline excretion rate of inorganic sulfate in the senescent animals (0.38 +/- 0.25 mumol/min/kg, mean +/- S.D., n = 7) was significantly (P < 0.05) lower than that observed in the young animals (0.64 +/- 0.19 mumol/min/kg, n = 8). There was no difference in the turnover rate constant, as measured by the change in specific activity of urinary [35S]sodium sulfate, for the endogenous sulfate pool in old and young animals. Following acetaminophen administration, plasma sulfate concentrations declined similarly in young and old animals. Under the conditions of relative inorganic sulfate depletion, the renal excretion rate of inorganic sulfate decreased to zero in 7 of 8 young rats, whereas the old animals continued to excrete sulfate anion at an average rate of 23% of the baseline value. Aged animals have a defect in active tubular renal reabsorption of sulfate under conditions of sulfate depletion. Age-related changes in the total sulfate excretion rate may reflect changes in the metabolic fate of endogenous sulfate rather than changes in the endogenous production rate of this anion. PMID- 8469019 TI - A comparison of methods for estimating mortality parameters from survival data. AB - The Gompertz mortality function, Rm = R0e alpha t, is frequently used to describe changes in mortality rate (Rm) with time (t). In this paper, four methods for determining the best fit values of the two parameters, R0 and alpha, are compared. Three of the four methods use the Gompertz mortality function with mortality rate estimates derived from survival data to determine the best fit values for the two parameters. All three confront problems. The fourth method uses the Gompertz survival function, which can be derived from the Gompertz mortality function and which allows one to use survival data directly. It thereby avoids the problems and generally gives the best estimates for the two parameters. The use of the mortality function, with mortality rate estimates, confronts four distinct problems. One of these is caused by time intervals when zero organisms die. A second is caused by errors produced in estimating mortality rates from survival data. If too high a proportion of a population die in a given time interval, the mortality rate estimates are too low. A third problem is the sensitivity of the mortality-equation-based analyses to values at the end of the survival curve, where scatter in mortality values tends to be greater. A final problem occurs when time intervals greater than one time unit (day, week, year, etc.) are used in the analysis. Such problems with the use of mortality rates to estimate parameter values are revealed when the calculated parameters are used to produce a survival curve, or when known values of R0 and alpha are used to generate survival data. This paper introduces a non-linear regression analysis, using a Simplex algorithm to fit parameters R0 and alpha in the Gompertz Survival function and concludes that it gives more reliable and consistent results with a variety of data than do three methods that use the mortality function. PMID- 8469020 TI - Gene expression and aging. AB - Considerable amount of data has accumulated during the past few years showing several changes in gene expression as a function of age. However, the basic mechanism of aging still remains poorly understood. In this review, we have mainly analysed the data pertaining to the hypothesis that aging is associated with genetic instability and have attempted further to highlight the gaps that need to be bridged in order to have a clear picture of the aging phenomenon. Extensive investigations employing new and novel approaches are needed in future to elucidate the intricately interwoven patterns of molecular control that underlie the various aspects of gene expression during aging. PMID- 8469021 TI - Compensatory hypertrophy and training effects on the functioning of aging rat m. plantaris. AB - The influence of age, compensatory hypertrophy and training on isometric contraction characteristics of rat m. plantaris were investigated in 5-, 13- and 25-month-old rats. Each age group was subdivided into Control Not Trained, Control Trained, Operated Not Trained and Operated Trained groups. Run training was applied. The Operation i.c. denervation of synergists induced a 30% compensatory hypertrophy (P < 0.001). Age and training did not significantly affect muscle weight. The tetanic force was highest in 13-month-old and lowest in 25-month-old muscles as was the tetanic force/muscle weight (P < 0.001). Trained and hypertrophied muscles had increased tetanic force (P < 0.01), but tetanic force/muscle weight was not significantly affected. Twitch contraction time was longer in hypertrophied muscles than in controls (P < 0.001). Half relaxation time decreased with training (P < 0.05). Resistance to fatigue was increased in hypertrophied muscles as compared to controls (P < 0.04) and was lower in 5-month old than in 13-month-old muscles, but their fatigue resistance did not differ from the 25-month-old muscles. Each age group showed comparable effects of training and hypertrophy on the contraction characteristics. These results indicate that the force generating capacity of the M. plantaris was optimal in the 13-month-old animals compared to the other age groups. Furthermore, our data show that aged muscles react in a similar way to increased functional demand as muscles of younger age. PMID- 8469022 TI - Age-dependent differences of ATP breakdown and ATP-catabolite release in ischemic and reperfused hearts. AB - The hearts of young (6 months) and aged (24 months) rats, paced at a frequency of 300 bpm, were perfused by the Langendorff technique and subjected to: 20 min of equilibration perfusion, 30 min of global ischemia (95% reduction of the coronary flow) and 20 min of reperfusion. The control group was equilibrated for 20 min and then aerobically perfused for 50 min. After 20 min of stabilization, ATP and ADP levels and the adenine nucleotide pool were significantly higher in young than aged hearts (15% increase), but no modifications were found between the two age groups after 50 min of aerobic perfusion. Even the energy charge did not change under aerobic conditions. At the end of the ischemic period the levels of ATP and ADP decreased to a similar extent in young and aged hearts. After 20 min of reperfusion the myocardial level of ATP remained lower in comparison to the preischemic and control values in both age groups. At the end of the reperfusion there was a decrease in energy charge and creatine phosphate levels in the aged group in respect to the young group. The concentrations of adenosine, hypoxanthine and xanthine in coronary effluents did not change during ischemia and reperfusion irrespective of the age of the animals. On the contrary, the release of uric acid during ischemia and reperfusion was greater in aged than young hearts (90% increase). Moreover, the level of inosine in perfusates during the ischemic period was significantly lower in the 24-month-old group (30% decrease). These results are in accordance with the increased purine nucleoside phosphorylase activity and the decreased hypoxanthine phosphorybosyl-transferase activity found in the myocardium of the aged vs. young rats at the end of the reperfusion period. These data indicate that in the aged rat hearts, when exposed to ischemic and reperfusion conditions, there is a modification of purine breakdown which leads to a greater production of uric acid in respect to that found in young hearts. PMID- 8469023 TI - Evidence for age-dependent impairment of antiviral 2',5'-oligoadenylate synthetase/ribonuclease L-system in tissues of rat. AB - The 2',5'-oligoadenylate system (2-5A system) has an essential role in the establishment of the antiviral state of cells exposed to virus infection. The effects of 2-5A are mediated by a 2-5A-dependent ribonuclease (RNase L) which cleaves viral RNA. A study of 2-5A metabolism in different tissues of rats of different age (newborn: 1-day-old; young adult: 2- to 3-month-old; middle-aged adult: 12-month-old; and old: 32- to 33-month-old) revealed that the activities of the 2-5A metabolic enzymes alter during aging and development. We demonstrate that soluble 2-5A synthetase activity strongly increases after birth, reaching maximal levels in young adult and middle-aged adult animals and then significantly decreases with age; the age-dependent decrease was found also for the nuclear matrix-associated enzyme. In contrast, the activity of 2',3' exoribonuclease which inactivates 2-5A increases by 3-fold with age. The decrease in 2-5A synthetase activity and increase in 2-5A nuclease activity were found to result in a decrease in the cellular 2-5A content with age. The RNase L which is activated by 2-5A also changes age-dependently. The amount and activity of this enzyme were determined in cross-linking experiments, in nitrocellulose binding assays and in the ribosomal RNA cleavage assay. The livers of old rats displayed a 5- to 6-fold decrease in RNase L activity compared to the adult animal groups, whilst the amount of the enzyme did not change significantly during aging with the exception of a drop by 30% in the nuclear matrix fraction. From these results we conclude that the antiviral activity of the 2-5A system is impaired in old cells with the consequences that virus production cannot be efficiently suppressed. PMID- 8469024 TI - Lung glutathione reductase induction in aging catalase-depleted frogs correlates with early survival throughout the life span. AB - A comprehensive experimental study on free radical-related parameters was performed in the lung throughout the life span of 220 initially young or old frogs. No age related differences were found transversely or longitudinally for lung superoxide dismutase, catalase, Se-dependent and -independent glutathione peroxidases, glutathione reductase, GSH, GSSG, or GSSG/GSH ratio. Continuous catalase depletion with aminotriazole led to glutathione reductase induction in the lung after 14.5 months of experimentation. This was accompanied by a great increase in survival rate of treated animals in relation to controls (especially in the old group). After 26.5 months of experimentation, glutathione reductase induction was lost and GSSG/GSH values tended to increase. This was followed by a 3-month long period of acute decrease in survival rate of treated animals. It is suggested that a high antioxidant/prooxidant balance is of protective value against causes of early death and can possibly be used in the future (when appropriately controlled) to increase the number of healthy years of the normal life span. PMID- 8469025 TI - Red blood cell age dependent modifications of inositol 1,4,5-trisphosphate. AB - The level of inositol 1,4,5-trisphosphate (Ins1,4,5P3) was determined in human and rabbit red blood cells of different ages. In human erythrocytes, fractionated by discontinuous density gradient centrifugation, Ins1,4,5P3 was 290 nM in the 0.3% low density (youngest) cells compared to values of 107 nM in the whole red blood cell population. A progressive increase in Ins1,4,5P3 was then observed during erythrocyte aging from values of 63 nM in mature erythrocytes to 128 nM in the oldest cells. Determinations of Ins1,4,5P3 in rabbit erythrocytes provided values of 180 nM. Phenylhydrazine was administered to three animals to induce reticulocytosis. Ins1,4,5P3 in rabbit reticulocytes was significantly lower than in the whole red cell population, remained lower in young red blood cells and then increased to normal values during cell maturation. These results provide evidence for an increase of Ins1,4,5P3 during red blood cell aging and could contribute to explain the age-dependent loss of deformability and of Ca2+ homeostasis of these cells. PMID- 8469026 TI - Pulmonary pentane excretion increases with age in healthy subjects. AB - Excessive lipid peroxidation occurs in various diseases. However, even in health low levels of lipid peroxidation can be detected by measuring the pulmonary excretion of pentane. Lipid peroxidation has been postulated to be one of the causes of the ageing process. In order to test whether pentane excretion is related to age, we measured breath pentane in 47 healthy subjects (ages 21-79). We also measured serum levels of the antioxidants tocopherol, retinol, lycopene, beta carotene, ascorbate and zinc. We found that pentane excretion significantly (P < 0.05, r = 0.32) increased with age. Of the six antioxidants measured, only lycopene decreased significantly (P < 0.05, r = -0.47) with age, however, this decline did not statistically correlate with pentane excretion. The remaining five antioxidants either remained stable or increased over the age range studied. We conclude that lipid peroxidation, as assessed by pentane excretion, increases with advancing age but that this increase is independent of dietary antioxidant levels. PMID- 8469027 TI - Age-related changes in collagen gel contraction by cultured human lung fibroblasts resulting in cross-over of contraction curves between young and aged cells. AB - We examined the effects of population doubling levels on collagen gel contraction by human lung fibroblasts (TIG-1). The sizes of gels at day 4 of culture, when the number of cells was the same as the initial number, were smaller with young cells than with aged cells. Therefore, retractive force had decreased with in vitro cellular aging. On the other hand, the lag time until gel contraction began became shorter with aging, resulting in the cross-over of contraction curves of young and aged cells. Morphological changes, such as pseudopodia protrusion, were suppressed in collagen gel. The surrounding collagen fibrils prevented young cells from moving more than aged cells. The weakened omnidirectional interaction with collagen fibrils on the entire surface of aged cells might result in an earlier occurrence of morphological change and, thereby, gel contraction. PMID- 8469028 TI - A mathematical model of the effect of aging on bone marrow cells colonizing the thymus. AB - The process of T cell generation in the thymus involves complex cell-cell interactions between the various types of thymic stromal cells, thymocyte progenitors, thymocytes at different stages of differentiation and external factors. We applied the tool of mathematical modelling to analyze hypotheses and direct experiments concerning mechanisms underlying the observed developmental inferiority of bone-marrow thymocyte progenitors from old mice. Previous experimental data showed that lower cell numbers were obtained from old bone marrow-derived thymocyte progenitors, compared to young bone marrow-derived progenitors, when colonizing simultaneously the same fetal thymus. In this study, simulations based on the mathematical model indicate that the developmental inferiority of old bone marrow-derived progenitors cannot be explained by a change in a single parameter, such as the observed differences in progenitor frequency, an increase in cell cycle duration, a reduction in the fraction of proliferating cells in old age, and/or an increase in the rate of cell death. We have performed experimental measurements of the fractions of cycling cells. No significant difference was found between these fractions in young and old bone marrow-derived thymocytes. The difference in developmental patterns of young and old bone marrow-derived thymocytes may be due to a combination of more than one mechanism, possibly including interactions between competing thymocytes of old and young bone marrow origin. PMID- 8469029 TI - The in vitro senescence of human T lymphocytes: failure to divide is not associated with a loss of cytolytic activity or memory T cell phenotype. AB - Normal human T lymphocytes, activated in vitro and cultured in the continuous presence of the growth factor interleukin 2 (IL2), have a limited proliferative potential. Senescent T cell cultures will not proliferate, even if restimulated by the original allogeneic stimulator cells. However, we have now observed that such restimulation induces an increase in the percentage of cells expressing the 55 kDa chain of the IL2 receptor (IL2R alpha, CD25) without any associated increase in cell number. A younger culture, which showed a comparable increase in CD25, underwent two population doublings in the same time period after restimulation. The senescent cultures, (primarily of the CD8+, cytotoxic/suppressor, phenotype), were also found to be highly potent and specific effector cells in a 51chromium release assay for cytolytic activity. Furthermore, senescent cultures maintain the surface phenotype of memory T cells. These findings demonstrate that while senescent T cells are unable to proliferate in response to restimulation or to IL2, they are able to recognize the foreign stimulator cells and to initiate an otherwise normal T cell response. Our results lend support to the hypothesis that in vitro senescence is not associated with a generalized decline in functional activity in a differentiated cell type, but with a specific event which limits cell division. Thus, the long term T lymphocyte culture system will be useful for studying the mechanism by which proliferation is blocked in these, apparently, post-mitotic cells. PMID- 8469030 TI - Effects of wheel running on glucose transporter (GLUT4) concentration in skeletal muscle of young adult and old rats. AB - We examined the effects of voluntary exercise on glucose transporter concentration in skeletal muscle from young adult and old female Long-Evans rats. Rats had free access to voluntary running wheels beginning at 4 months of age or remained sedentary. Exercising rats ran approximately 7.5, 6.2, 5.6 and 5.3 km/day during their 6th, 8th, 9th and 10th month of age, respectively. During the 23rd, 24th and 25th month of age running distance averaged 3.0, 2.8 and 2.4 km/day, respectively. At 10 and 25 months of age, glucose transporter protein concentration was assessed in epitrochlearis and flexor digitorum brevis muscles with a polyclonal antibody directed against the GLUT4 transporter isoform. GLUT4 protein concentration was not altered by the aging process (i.e., comparing 10- and 25-month-old rats) in either muscle type. Wheel running increased GLUT4 protein concentration by 45% in epitrochlearis muscles of 10-month-old rats relative to age-matched sedentary controls. The training-induced adaptation in GLUT4 protein was no longer present at age 25 months, probably because the running distance had declined by 50%. In the flexor digitorum brevis, exercise did not alter GLUT4 concentration at either 10 or 25 months, presumably due to insufficient recruitment of this muscle during wheel running as assessed by measurement of citrate synthase and hexokinase enzyme activities. Wheel running induced cardiac and soleus muscle hypertrophy in 10- and 25-month-old rats. In summary, voluntary wheel running can induce an increase in skeletal muscle GLUT4 protein concentration in adult rats. Older rats that run less exhibit cardiac and soleus muscle hypertrophy, but do not maintain an elevated GLUT4 protein concentration in the epitrochlearis muscle. Aging does not alter GLUT4 protein concentration in the epitrochlearis or FDB muscles. PMID- 8469031 TI - Stereoselective pharmacokinetics of atenolol in the rat: influence of aging and of renal failure. AB - The pharmacokinetics of R- and S-atenolol after intravenous administration of racemic atenolol were studied in 3-, 12- and 24-month-old rats and in 3-month-old rats with renal failure induced by uranyl nitrate. In all age groups, the area under the plasma concentration-time curves is higher for R- than for S-atenolol; volume of distribution, total clearance and renal clearance are lower for R atenolol than for S-atenolol, but the differences are small. In function of age there is for both enantiomers a significant increase in AUC, due, at least in part, to a decreased renal clearance; the effect of aging is not stereoselective. In rats with renal failure, the AUC of both enantiomers increases, due mainly to a decrease in renal clearance, but to a lesser degree also to a decrease in nonrenal clearance. For both enantiomers, the volume of distribution decreases and the half-life increases in the uraemic rats. The total amount of both enantiomers excreted in the urine is decreased in the rats with renal failure. There are no stereoselective effects of treatment of the rats with uranyl nitrate. PMID- 8469032 TI - Macrophages suppress lectin-induced proliferation of lymphocytes from aged rats. AB - Splenocytes from old rats exhibit a significant reduction in proliferative responses to Con A. This defect can be overcome by passing the cells over nylon wool, which suggests that nylon wool adherent cells contribute to the reduction in proliferation of mixed cell populations from aged rats. To examine the potential role of macrophages in this process, thioglycollate-elicited peritoneal macrophages were added to Con A-activated spleen cells from young and old rats. Addition of as few as 3% macrophages suppressed proliferation of Con-A-activated splenocytes and this inhibition was significantly greater if either the macrophages or spleen cells were derived from aged rats. Although prostaglandin E2 (PG-E2) inhibited the proliferation of splenocytes and nylon-wool enriched splenocytes from 3-month-old animals, its suppressive effects were much greater on Con A-activated lymphocytes derived from 24-month-old rats. Addition of catalase to deplete macrophage-derived H2O2 resulted in greater augmentation of Con-A-induced proliferative responses of splenocytes from old rats than those from young rats. TGF-beta 2, but not TNF-alpha, also significantly suppressed the proliferation of Con A-activated splenocytes to a greater degree in aged than in young rats. Since macrophages are known to release PG-E2, H2O2 and TGF-beta 2 after stimulation with Con A, these data support the idea that T cells within the splenocyte population become increasingly susceptible during aging to inhibitory products released by macrophages. PMID- 8469033 TI - Age-related reduction of reflex bradycardia in conscious rats by catecholaminergic nucleus tractus solitarius lesions. AB - To determine whether catecholaminergic lesions in the nucleus tractus solitarius (NTS) have age-related baroreflex effects, we compared conscious 3-month- and 14 month-old rats pretreated with either 6-hydroxydopamine (6-OHDA) or vehicle injected into the NTS. Body weights fell immediately in both age groups, but after 2 weeks the weight loss persisted only in 14-month-old rats. Mean pressures and heart rates, though diminished after 3 days, were later elevated slightly in 3-month- but not in 14-month-old rats. Two weeks after 6-OHDA pretreatment, reflex tachycardia was reduced in both age groups, but reflex bradycardia was reduced only in 3-month-old and not in 14-month-old rats. Corresponding changes in vehicle-treated rats were not significant. Because 6-OHDA induced lesions in the NTS inhibited reflex bradycardia selectively at 3 but not at 14 months of age, our results suggest that catecholaminergic mechanisms in the NTS for regulating reflex bradycardia become impaired with age. PMID- 8469034 TI - Longitudinal Gompertzian analysis of non-Hodgkin's lymphoma mortality in the US, 1979-1988: demonstration of the environmental basis for rising overall mortality. AB - Between 1979 and 1988, annual crude non-Hodgkin's lymphoma mortality rates (per 100,000) in the United States increased from 3.43 to 6.34 among men (an 85% increase in only 10 years) and, among women, increased from 2.82 to 5.71 (a 102% increase). Age-specific mortality rates for non-Hodgkin's lymphoma from 1979 through 1988 were subjected to longitudinal Gompertzian analysis, a method that may be able to identify and distinguish among genetic, environmental and competitive influences upon evolving mortality trends. The results of this analysis suggest that the basis for the dramatic rise in non-Hodgkin's lymphoma mortality is due to worsening environmental influences. The capability to distinguish between environmental and competitive influences upon evolving mortality patterns has significant public health policy implications. PMID- 8469035 TI - The age-dependent proliferation of rat aortic smooth muscle cells is independent of differential splicing of PDGF A-chain mRNA. AB - Arterial smooth muscle cells (SMC) from old rats proliferate in vivo (after injury) and in vitro more rapidly than smooth muscle cells from young rats. We previously observed that SMC from old rats contained more PDGF-like growth factor activity than did young SMC. We therefore tested the hypothesis that age-related differences in type of PDGF A-chain gene expression might be responsible for the difference in growth factor activity, since PDGF B-chain gene is minimally expressed both in young and old SMC. Specifically we tested if the old SMC predominantly expressed the long form of the A-chain mRNA, leading to autocrine stimulation by cell-associated PDGF AA-homodimers. A partial cDNA for the rat PDGF A-chain was cloned and sequenced; it is highly conserved compared to the human PDGF-A chain and similarly has two forms, a long form containing all exons, which tends to remain cell-associated and a short form lacking exon 6, which tends to be secreted. Different tissues of both young and old animals express different ratios of these two forms of PDGF-A. However, the relative expression of the different mRNA forms does not change with age, suggesting that differential splicing of PDGF-A and accumulation of cell-associated PDGF A-chain does not determine the enhanced growth potential of old rat SMC. PMID- 8469036 TI - Changes with ageing in total dolichol and dolichol fractions in Drosophila. AB - Since it is unclear how the concentration of dolichol fractions change with ageing in mammals, we have examined the changes in another organism, Drosophila. Dolichol extracted from Drosophila melanogaster was found to consist of three fractions composed of 15, 16 and 17 isoprene units. The total dolichol content of female flies maintained at 25 degrees C increased with ageing between 0 and 64 days of adult age but the change was not significant. The total dolichol content of male flies decreased with ageing but the decrease was not significant. The relative amounts of the three different dolichol fractions in both male and female flies also failed to show any significant ageing-related change. The greatest amount of dolichol was found in the 16 isoprene unit fraction representing 67.2% of the total dolichol in male flies and 65.4% in female flies. Increased dietary dolichol had little or no influence on the life span of Drosophila when given either during the developmental or adult stages. PMID- 8469037 TI - [Surgical wound infection: the risk factors and a predictive model]. AB - BACKGROUND: The identification of the factors associated with infection of the surgical wound and the groups of patients with greatest risk of developing the same may aid in the elaboration of prevention strategies. METHODS: A prospective follow up study of a group of 1,143 patients admitted to general and digestive surgical departments in the Ramon y Cajal Hospital over a period of 7 months was carried out to determine the accumulated incidence of infection of the surgical wound and quantify the associated risk factors. A mathematical model was developed by logistic multiple regression analysis allowing the identification of groups of patients with high risk of infection which were internally evaluated posteriorly. RESULTS: Surgically intervened patients (70% of those admitted) developed a mean of 11 wound infections out of 100 patients. Five independent factors (age, surgical classification, length of intervention, presurgical stay, and presence of a central route) were associated to increased risk of infection. CONCLUSIONS: The factors associated with surgical wound infection identified in this study are related to the degree of wound contamination, the intrinsic risk of the patients and quality of health care. The model obtained is more efficient than the traditional surgical classification for the identification of groups of patients with high risk of infection. PMID- 8469038 TI - [A clinical study of the verapamil and captopril combination in hypertensive patients uncontrolled by monotherapy. An evaluation by recording the 24-hour ambulatory blood pressure]. AB - BACKGROUND: By measuring ambulatory blood pressure monitoring (ABPM), the pharmacologic association of verapamil plus captopril in essential hypertensive patients not responding to isolated monotherapy of these drugs was studied since a synergism has been described between these two drugs. METHODS: A lineal clinical trial with a previous period of selection (PeSe) in which verapamil and captopril were administered in two consecutive phases was carried out in 57 essential hypertensive patients of 52 +/- 19 years of age with those controlling their blood pressure (BP) being excluded. Following a lavage phase the remaining subjects were included in the experimental period (ExPe) in wash out the association of verapamil 120 mg+captopril 25 mg was administered and if the BP was not controlled this was increased to 240 mg + 50 mg, respectively. ABPM was performed prior to and at the end of the ExPe. RESULTS: Of the 57 patients 21 were excluded in the SePe due to control or adverse effects. Of the 26 individuals who passed into the ExPe 20 presented mild-moderate HTA (M-HTA) and 6 severe HTA (S-HTA). In the M-HTA group, the reduction of BP (in mmHg) was 157 +/- 15/106 +/- 5 to 147 +/- 12/97 +/- 7 (p < 0.05/p < 0.001), five controlled BP, in the remaining subjects the reduction in the following phase was 150 +/- 11/100 +/ 6 at 136 +/- 11/93 +/- 6 (p < 0.01/p < 0.01). In the S-HTA group the BP descended in the ExPe from 184 +/- 15/121 +/- 6 to 167 +/- 24/107 +/- 10 (p < 0.05/p < 0.05). The 24 hour measurement of BP in the ExPe decreased from 140 +/- 13/96 +/- 8 to 124 +/- 10/86 +/- 7 (p < 0.001/p < 0.001). BP descended significantly in all the hours with the exception of the hours 24, 1, 6, 7, and 5. CONCLUSIONS: The association of verapamil-captopril demonstrates efficacy and synergism in hypertensive patients previously uncontrolled by monotherapy of these drugs. PMID- 8469039 TI - [A multicenter study of infection with human immunodeficiency virus type-2 (HIV 2) in Spain (1991). The Spanish Group for the Study of HIV-2]. AB - BACKGROUND: To January 1991 thirteen cases of HIV-2 infection had been reported in Spain. Paradoxically, neighboring countries, i.e. France and Portugal, have reported more than one thousand cases, and are the most HIV-2 prevalent areas outside West Africa. We report the results of a prospective, nationwide study on the prevalence of HIV-2 infection conducted in Spain in 1991. In addition, an evaluation of testing methodologies is made. METHODS: Sera collected from 8,073 individuals at high-risk for HIV infection were screened by a combined HIV-1 plus HIV-2 ELISA. Reactive samples were further evaluated by three tests, as HIV-1 Western blot (WB), HIV-2 specific WB, and a synthetic peptide assay immuno-dot (Pepti-lav, Pasteur). RESULTS: Fifteen (0.18%) individuals met criteria of HIV-2 infection in both specific WB and SPA. Four (27%) of them showed reactivity to both HIV-1 and HIV-2, and the dual infection was confirmed by polymerase chain reaction (PCR) in 2 out of 3 available samples. The SPA showed higher sensitivity and specificity than WB in the diagnosis and distinction of HIV-1 and HIV-2 infections. CONCLUSIONS: To January 1992, 28 cases of HIV-2 infection have been described in Spain. All but two were African immigrants. The first cases of HIV-1 plus HIV-2 coinfection have been identified. In HIV high-risk populations, SPA may provide an excellent alternative to WB to confirm ELISA reactive samples. PMID- 8469040 TI - [Why surgical wounds become infected]. PMID- 8469041 TI - [Patients' rights: the practical problems]. PMID- 8469042 TI - [The lung transplant]. PMID- 8469043 TI - [The growth hormone and kidney failure: new physiopathological aspects and therapeutic possibilities]. PMID- 8469044 TI - [The advantages of providing the standard error in communicating the results of original biomedical studies]. PMID- 8469045 TI - [The spontaneous cure of acromegaly after pituitary apoplexy: a report of 2 cases]. PMID- 8469046 TI - [Typical migraine and thalidomide]. PMID- 8469047 TI - [Bacterial enteropathogens and antimicrobial resistance in Zamora: the usefulness of fluoroquinolones]. PMID- 8469048 TI - [The attitude of hospital nursing professionals toward drug-addicted patients]. PMID- 8469049 TI - [The translation of abstracts into English]. PMID- 8469051 TI - [The company physician is needed and beneficial]. PMID- 8469050 TI - [Don't let your life go up in smoke. Ban the tobacco advertisement, introduce age limit]. PMID- 8469052 TI - [Defend the territorial responsibility of primary health care workers]. PMID- 8469053 TI - [The right to designate family physicians--a threat or possibility?]. PMID- 8469054 TI - [An open letter to the National Board of Health and Welfare about pediatric cardiology]. PMID- 8469055 TI - [To widen or not to mix]. PMID- 8469056 TI - [Keep the courses of psychotherapy?]. PMID- 8469057 TI - [The effects of cervical manipulation are not proven]. PMID- 8469058 TI - [Warm baths and sauna during early pregnancy. It is not sure there is a risk of abnormalities]. PMID- 8469059 TI - [Successful splenectomy in HIV thrombocytopenia]. PMID- 8469060 TI - [Painful alliance]. PMID- 8469061 TI - [Warning! Epidural stimulator caused false asystole]. PMID- 8469063 TI - [The care of drug addicts could be much better]. PMID- 8469062 TI - [Only few families with handicapped children get help to relieve pressure]. PMID- 8469064 TI - [Where are the patients committed to treatment by the court?]. PMID- 8469065 TI - [Politicians and benzodiazepines]. PMID- 8469066 TI - [The concept of dementia--does it enlighten or confuse?]. PMID- 8469067 TI - [Be careful with fax!]. PMID- 8469068 TI - [Allergy. A comment to a consensus statement on a disease group costly to society]. PMID- 8469069 TI - [Post-infection HIV vaccination. More clinical trials are initiated in Sweden]. PMID- 8469071 TI - [Does health personnel prefer alternative medicine?]. PMID- 8469070 TI - [The WHO statement on strategies of HIV vaccinations: field trials in developing countries should await studies of the effects]. PMID- 8469072 TI - [Cataract surgery. What is beneficial for the patient?]. PMID- 8469073 TI - [Cataract surgery. What is the need and who will perform the surgery?]. PMID- 8469074 TI - [Rehabilitation of patients with coronary disease. A live-in alternative is as positive for women as for men]. PMID- 8469075 TI - [Toxic shock syndrome in a young child. A severe condition caused by a minor injury]. PMID- 8469076 TI - [Injuries are reduced by air bags. But seat belts are still to be used]. PMID- 8469077 TI - [Occupational conditions of chief surgeons. Does a heavy work schedule interfere with sleep and family life?]. PMID- 8469078 TI - [An old man writes a wish list to the physician. Criticism against the new advises on the treatment of hypertension. Recommended treatment of hypertension in the elderly]. PMID- 8469079 TI - [Psychodynamic therapy has had its day]. PMID- 8469080 TI - [An inquiry on medical teaching. Pedagogic qualifications are important]. PMID- 8469081 TI - Medications to treat alcoholism? PMID- 8469082 TI - Chronic polyarthralgia in adults. AB - Rheumatologists often see patients with musculoskeletal complaints who do not always have symptoms and findings that fit into recognized syndromes. Twenty-two such patients with chronic polyarthralgias, including eight with a positive test for ANA (anti-nuclear antibodies), seen over a seven-year period, did not meet criteria for classification or diagnosis of any recognized rheumatologic syndromes. The mean follow-up since onset of symptoms was 77.5 months (range, 13 276 months). During this time, none of the patients' conditions evolved into any previously recognized syndromes. This report on the study of these 22 patients emphasizes the existence of such patients and comments on their prognosis and treatment. PMID- 8469083 TI - Lyme disease in outdoor workers on Assateague Island: high tick-exposure but low disease risk. AB - Lyme disease is endemic to the Assateague Island area. Using a questionnaire and serosurvey, we examined the extent of tick exposure, compliance with recommended Lyme disease personal preventive activities, and risk of the disease in 86 outdoor workers on Assateague Island before and after the summer of 1989. Despite high self-reported tick exposure and relatively long employment durations on the island, there was no evidence of current or past infection with Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease knowledge and use of several personal strategies were high, but compliance with these preventive strategies was not universal. These data suggest that even in this high-risk population, intensive educational efforts are necessary to encourage Lyme disease preventive behavior, but the current level of compliance may have decreased the risk of Lyme disease on the island. PMID- 8469084 TI - The residents' computer bulletin board system: results of a 23-month pilot study. AB - The Residents' Computer Bulletin Board System (RBBS) originated as an offshoot of a research project designed at a 1988 meeting of Baltimore's chief medical residents. Beginning on March 1, 1989, RBBS offered electronic mail, bulletins, file transfers, newsletters, and data collections to physicians-in-training. It operated for 695 days before ResNet, sponsored by the American College of Physicians, superseded it. This report details how medical students, residents, and fellows used this electronic means of communication and offers some conclusions about the elements that future computerized bulletin board systems should have to succeed. PMID- 8469085 TI - Body stalk deformity in a twin pregnancy: case report and review. AB - Body stalk deformity is a variety of the limb-body wall complex (LBMC)--the rare, complicated, congenital process believed to result from early rupture of the amnion and vascular disruption. Here we report a case of this anomaly in a twin pregnancy and describe the prenatal ultrasound findings. PMID- 8469086 TI - A brief history and discussion of certain mycotic infections and their importance to physicians. AB - Mycotic infections are common and their incidence is increasing. They can be difficult to distinguish from other infections, particularly tuberculosis, but there are numerous clinical clues that can help suggest the presence of systemic mycoses. Histoplasma skin tests, serologic tests, and agent isolation can aid in the confirmation of a fungal infection. Clinical considerations must be put in the proper perspective before a definitive treatment is proposed. Specific chemotherapy is often curative. PMID- 8469087 TI - Imaging case of the month. Acute cholecystitis. PMID- 8469088 TI - The importance of early diabetic retinopathy detection. PMID- 8469089 TI - Diagnosis and treatment of depression in late life: summary of the NIH consensus statement. PMID- 8469090 TI - The Library of the Medical and Chirurgical Faculty of Maryland. PMID- 8469091 TI - Medical records that guide and teach. 1968. PMID- 8469092 TI - Data communications. PMID- 8469093 TI - Improving PC efficiency by accelerating hard drive performance. PMID- 8469094 TI - Trends in journalism. PMID- 8469095 TI - Lawrence L. Weed and the problem-oriented medical record. PMID- 8469096 TI - One man's meat. PMID- 8469097 TI - Another man's poison. PMID- 8469098 TI - Estimating the number of physicians using computers. PMID- 8469099 TI - The medical record: problem or solution? PMID- 8469100 TI - Probability and medical decision making: a politically incorrect view. PMID- 8469101 TI - A neural network that predicts psychiatric length of stay. AB - We developed a neural network to predict length of stay after admission to a state psychiatric hospital. The network was trained with data from 1064 cases randomly selected over a 3 1/2-year period, and its accuracy was tested against actual length-of-stay patterns and predictions made by a team of clinicians 72 hours after admission. The network performed at least as well as the team of clinicians. Successful prediction of length of stay could result in more appropriate use of services, more timely initiation of treatment, better resource planning, and cost control--highly sought dividends in an era of diminishing fiscal resources. PMID- 8469102 TI - Computer-based patient education: a progress report. AB - Computer-based teaching can help patients make informed decisions and protect both patients and physicians from the serious consequences of poor communication. This article discusses the benefits of computer-based patient education and its role in the emerging field of "patient informatics." PMID- 8469103 TI - Novel microsurgical model of experimental vascular neointimal hyperplasia. AB - Neointimal hyperplasia is a common finding after trauma to blood vessels and also as a primary change in atherosclerosis. In this study we have developed a simple model, using microsurgical techniques, for the initiation of neointimal hyperplasia in the rat. In 24 Wistar rats, a 2 mm-diameter arteriotomy in the aorta was repaired with a "patch" of iliolumbar vein, using eight evenly spaced 10-0 Ethilon sutures. The patch overlapped the edges of the arteriotomy, and the sutures fastened the patch to the subjacent aorta. At 2, 6 and 12 weeks after surgery, the venous patch grafts and segments of the adjacent aortae of eight rats were removed. One-half of the specimens were analyzed by scanning electron microscopy and the other one-half by light microscopy. All patch grafts were surgically successful. Endothelial cells regenerated to cover the patch within 2 weeks of insertion. By 6 weeks after surgery, neointimal hyperplasia, consisting predominantly of smooth muscle, had developed in all patches to a thickness that was not significantly different from that of the adjacent aorta. These findings are consistent with data from other more complex experimental models of neointimal hyperplasia in the rat. We consider that this venous patch technique is a simple but effective model for the initiation of neointimal hyperplasia in the rat and may easily be used to study the experimental effects of various injurious or therapeutic agents on neointimal hyperplasia. PMID- 8469104 TI - Hemodynamic comparison of microsurgical closures for longitudinal arteriotomies. AB - Twenty-four femoral arteries in 12 rats were used to compare longitudinal and transverse closures in blood vessels approximately 1 mm in diameter. The closure techniques were applied to a simple longitudinal slit, 1 mm long, and to a longitudinal defect, 0.5 mm wide and 1 mm long. Comparisons were made of the change in pre- and postrepair flow velocities, recorded every 5 min using a 20 MHz pulsed Doppler velocimeter. Maximum reductions in flow velocity (linearly related to volume flow) were 10% and 29% for the longitudinal and transverse repairs, respectively, when applied to the longitudinal slit, and 65% and 19%, respectively, when applied to the larger arteriotomy. An analysis of variance indicates that the differences in the normalization of flow velocities during the immediate postrepair period are significant (P < 0.05). We conclude that optimal flow normalization is achieved by applying the longitudinal repair to the simple slit and the transverse repair to the larger arteriotomy. PMID- 8469105 TI - Microvascular transplant of the gastrocnemius muscle in rats. AB - The rat gastrocnemius muscle can serve as a vascularized, innervated muscle transplant model. To establish the anatomic and technical details of this model, we performed ten gastrocnemius transplants and collected data on muscle weight, dimension, and vessel caliber from each muscle. The muscle, consisting of medial and lateral heads, is supplied by pairs of sural vessels averaging 0.2 mm in diameter. These vessels, however, can be taken in continuity with the femoral vessels (averaging 1.0-1.6 mm in diameter), which are used for transplantation. The muscles weighed an average of 2.8 g, and the average pedicle length was 24 mm. Eight of ten transplanted muscles were viable with intact circulation at 72 hr. The gastrocnemius transplant was technically reliable, and the muscle bulk and contour could allow biochemical and functional studies. Donor site morbidity limits this model to transplantation studies. PMID- 8469106 TI - Free skeletal muscle transplantation to an infarction area: an experimental study in the dog. AB - In plastic surgery, free skeletal muscle flaps are used for treatment of non healing injuries like chronic osteitis or radiation ulcers. We wanted to evaluate if the neoangiogenesis induced by these flaps can also constitute a method for revascularization in ischemic heart disease. In diffuse small vessel coronary heart disease, patients are not suitable for bypass surgery because it is impossible to create a microanastomosis with the coronary artery. As an alternative, a free striated muscle flap, transplanted onto the heart, can constitute a source of neovessels. With the induction of extra-intracardial collaterals that develop within 4 weeks after transplantation of the flap, a new surgical approach may be offered to those patients. Our experimental work was performed with 20 dogs. In these, a myocardial infarction of the anterior wall was selectively produced using the Judkins-technique (Radiology 89: 815-824, 1967) for injection of Sephadex-microspheres. Four weeks later a free pectoralis muscle flap was transplanted onto the anterior wall of the heart. Arterial blood supply was achieved with an anastomosis with the internal mammary artery. The venous flow was directed into the right atrium. Four to eight weeks after surgery, the patency of the anastomosis was studied by angiography, showing patency in almost all surviving animals. Histological examination of the hearts revealed a prominent vascular network penetrating into the underlying myocardium. Corrosion cast preparations, as well as a postmortem angiography, showed even further penetration of the neovessels into the uninjured parts of the myocardium. Thus, myocardial revascularization may be achieved by transplantation of a skeletal muscle onto the heart. PMID- 8469107 TI - Nerve repair using freezing and fibrin glue: immediate histologic improvement of axonal coaptation. AB - Despite the fine microsurgical techniques available, injuries to peripheral nerves are still a surgical problem. Sutures placed in the epineurium or perineurium cause compression, brushing, and misdirection of endoneural tissue. A technique of nerve repair using freezing to trim the nerve and fibrin glue to coat it before thawing is described. The entire surgical repair procedure is carried out with the nerve stumps frozen. The observed axonal alignment with this technique was much better than that obtained by microsuture alone. PMID- 8469108 TI - Development of a mouse intestinal transplantation model. AB - We have recently developed a mouse intestinal transplantation model. The proximal segment of donor jejunum is transplanted into the recipient in a heterotopic position. End-to-side anastomoses are performed between donor aorta and recipient aorta and between donor portal vein and recipient inferior vena cava. Mortality rates were initially high due to shock, arterial thrombosis, and postoperative sepsis. Refinements in surgical techniques reduced these complications, resulting in a high rate of success. Important technical factors included (1) minimizing ischemic injuries to the graft in both the donor and the recipient, (2) using an aortic patch and elliptical aortotomy for anastomosis, (3) administering large volumes of crystalloid to maintain normal blood pressure during the donor and recipient surgeries, and (4) using broad-spectrum antibiotics as postoperative prophylaxis. The mice with isografts had normal intestinal function and histology when they were sacrificed 1 month after surgery. This new model of small bowel transplantation will be a useful tool to study the immunology of intestinal grafting at the molecular level. PMID- 8469109 TI - Management of major penetrating glass injuries to the upper extremities in children and adolescents. AB - Penetrating glass injuries are a common cause of severe neurovascular damage, both in adults and in children. Frequently, an innocent skin wound disguises the extensive nature of the injuries beneath. Nineteen children and adolescents (ages 3-16 years) with a mean age of 9 years who sustained upper extremity penetrating glass wounds were evaluated retrospectively in order (1) to determine the incidence of unappreciated significant neurologic, musculotendonous, or vascular injury; (2) to provide indications for intraoperative evaluation under anesthesia; and (3) to further define the role of microneurorrhaphy in this population. Twelve patients sustained injuries above the elbow and seven patients injuries distal to the elbow. Above the elbow, the structures injured in order of frequency were the median nerve (75%), the brachial artery (58%), the ulnar nerve (50%), the musculocutaneous nerve (33%), sensory nerves of the arm and forearm and venae commitantes (42% each), the radial nerve (25%), and the chords of the brachial plexus (8%). Distal to the elbow, the ulnar nerve was the most frequently involved (71%), followed by the ulnar artery (57%), the flexor carpi ulnaris (57%), the superficialis and profundus flexor tendons (43%), the median nerve (43%), and the palmaris longus and flexor carpi radialis (14% each). Early exploration is critical to successful management. Vascular repairs and or microneurorrhaphy were necessary in all cases. A detailed follow-up evaluation to assess the results of these repairs was carried out from 4 to 9 years postsurgery. There were no clinical problems related to the vascular reconstructions. The results of the nerve repairs in this small series of children and adolescents were remarkably good.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469110 TI - Strategies in pathogenesis: mechanistic specificity in the detection of generic signals. AB - The virulence genes of the plant pathogen Agrobacterium tumefaciens are induced by more than 40 low-molecular-weight phenolic compounds. The prevailing opinion is that (i) wound-derived phenols produced on breach of the integrity of the cell wall act as the initiating signal in a series of events which results in host cell transformation, and (ii) a classical membrane receptor, putatively VirA, is responsible for the recognition of all such phenolic inducers. Here, we argue that the discovery of the subset of inducers that are relatives of the dehydrodiconiferyl alcohol glucoside (DCG) growth factors redirects our attention to work on the plant wound as a site of cell division, and suggests that we further explore the implications of early work on the relationship between transformation efficiency and the status of the cell cycle of the host. In addition, we argue that the significant structural diversity allowed in the para position of the phenol ring of inducers suggests that a receptor-ligand interaction based solely on structural recognition is insufficient, but that recognition followed by a specific proton transfer event may be sufficient to explain vir induction activity. Hence, the specificity of the response of A. tumefaciens may be a consequence of the features required for a chemical reaction to occur on the receptor surface. Finally, we review affinity labelling studies which exploit this phenol detection mechanism and which provide evidence that the phenol receptor may be other than VirA, the sensory kinase of the two component regulatory system implicated in Agrobacterium virulence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469111 TI - In situ hybridization analysis of developmental stages of Pneumocystis carinii that are transcriptionally active for a major surface glycoprotein gene. AB - An abundant glycoprotein on the surface of Pneumocystis carinii, termed gpA or gp120, is thought to play a role in the interaction of this opportunistic pathogen with its host. Using RNA:RNA hybridization techniques, the in situ expression of gpA mRNA in developmental forms of the organism was investigated in a ferret model of P. carinii pneumonia. The results suggested that the relative abundance of gpA-specific mRNA was variable in different developmental stages of ferret P. carinii. P. carinii localized along the epithelial lining of alveoli were transcriptionally active. Immunocytochemical detection of gpA and Giemsa staining suggested that many of these organisms were trophic forms of P. carinii. While no detectable gpA mRNA signal was found in the majority of P. carinii cysts, a portion of identifiable cysts co-localized with significant levels of gpA mRNA signal. Differential staining of the cyst wall with Gomori's methenamine silver suggested that the transcriptionally active P. carinii cysts were the intermediate or precyst forms of the organism, while the cysts with no detectable mRNA signal were either mature or empty (excysted). Alveolar macrophages were observed surrounded by transcriptionally active organisms; however, no gpA transcriptional activity was detected within macrophages. Taken together, the results suggest that transcription of gpA occurs in forms of P. carinii that are actively replicating, and in close proximity or contact with, alveolar epithelial cells. PMID- 8469112 TI - Molecular analysis of a cytotoxin-converting phage, phi CTX, of Pseudomonas aeruginosa: structure of the attP-cos-ctx region and integration into the serine tRNA gene. AB - The Pseudomonas aeruginosa ctx gene encoding cytotoxin is carried by a temperate phage phi CTX. The genome of phi CTX is a 35.5 kb double-stranded DNA with cohesive ends (cos). It is unique in that the ctx gene and attP site of phi CTX exist very close to the respective cohesive ends. In this study, we determined the structure of this attP-cos-ctx region. The termini of phi CTX are 21-base 5' extended-single-stranded DNAs. The ctx gene is located 361 bp downstream of the left end (cosL). The attP core sequence of 30 bp exists only 647 bp apart from the right end (cosR). The attP-cos-ctx region contains six kinds of repeats and integration host factor-binding sequences and showed sequence-directed static bends, suggesting its potential to form a highly ordered structure. In addition, phi CTX was found to integrate into the serine tRNA gene which was mapped to the 43-45 min region on the P. aeruginosa chromosome. PMID- 8469113 TI - Deletion analysis of the SUP35 gene of the yeast Saccharomyces cerevisiae reveals two non-overlapping functional regions in the encoded protein. AB - SUP35 is an omnipotent suppressor gene of Saccharomyces cerevisiae coding for a protein consisting of a C-terminal part similar to the elongation factor EF-1 alpha and a unique N-terminal sequence of 253 amino acids. Twelve truncated versions of the SUP35 gene were generated by the deletion of fragments internal to the coding sequence. Functional studies of these deletion mutants showed that: (i) only the EF-1 alpha-like C-terminal part of the Sup35 protein is essential for the cell viability; (ii) overexpression of either the N-terminal part of the Sup35 protein or the full-length Sup35 protein decreases translational fidelity, resulting in omnipotent suppression and reduced growth of [psi+] strains; (iii) expression of the C-terminal part of the Sup35 protein generates an antisuppressor phenotype; and (iv) both the N- or C-terminal segments of the Sup35 protein can bind to 80S ribosomes. Thus, the data obtained define two domains within the Sup35 protein which are responsible for different functions. PMID- 8469114 TI - Functional analysis of the cya promoter of Bordetella pertussis. AB - The cyaA gene of Bordetella pertussis and of Bordetella bronchiseptica encodes a toxin which is a bifunctional protein exhibiting adenylate cyclase and haemolytic activities. In Bordetella, virulence factors are synthesized under the control of the bvg regulatory locus, in response to environmental signals. In Escherichia coli the cyaA gene is not expressed, nor is it activated by bvg indicating that the activation of cya by bvg is indirect. To characterize cis-acting regulatory regions required for the activation of the cyaA gene we constructed cyaA-lacZY fusions containing progressive deletions in the promoter upstream region and isolated promoter mutations by chemical and site-directed mutagenesis. Deletion analysis shows that a region extending from -569 to -136 bp upstream from the start site of transcription is required for transactivation by bvg, suggesting that multiple binding sites are involved in the activation of the cyaA promoter. No single or double mutations in the promoter upstream region were found which conferred inactive or bvg-independent Cya phenotype. A double mutation in positions +10 and +13, relative to the transcription start site, rendered the promoter bvg-independent and functional in E. coli. The constitutive mutations create a new transcription start site, 20 bp downstream from the wild-type site, by providing new -10 and -35 elements recognized by RNA polymerase alone. PMID- 8469115 TI - The virA promoter is a host-range determinant in Agrobacterium tumefaciens. AB - The limited host range (LHR) Agrobacterium tumefaciens strain Ag162 is an isolate with a narrow host range. Introduction of the wide host range (WHR) virA gene is essential for extending the host range to Kalanchoe daigremontiana. In this report we show that the region upstream of the ATG start codon is responsible for the LHR phenomenon and that this is probably due to the non-inducibility of the LHRvirA promoter. By comparing the characteristics of the LHR and WHR VirA receptor proteins, it was found that the LHR VirA protein is able to activate the WHR VirG protein in the presence of acetosyringone and that this acetosyringone dependent vir-induction is enhanced by the presence of D-glucose, as in the case of WHR VirA proteins. These results indicate that the domains, acting as receptors for sugars and phenolic signals, must be conserved between the LHR and WHR VirA receptor proteins. PMID- 8469116 TI - A 55 kDa antigen of Pneumocystis carinii: analysis of the cellular immune response and characterization of the gene. AB - Rat-derived Pneumocystis carinii contains a major antigen complex of 45-55 kDa. The fusion protein of a cDNA encoding the 3' portion of the 55kDa antigen, which had previously been shown to be recognized by serum antibodies of exposed subjects, was investigated for its ability to stimulate a cellular immune response. Rats exposed to P. carinii via the environment exhibited a vigorous proliferative response to the antigen whereas unexposed rats did not. The full length cDNA for a 55kDa antigen was cloned and found to contain a 1245bp open reading frame capable of encoding a 414-amino-acid peptide. The gene encoding this protein contained a single 39bp intron and transcribed a 1.45kb RNA message. The cloning and characterization of the 55kDa antigen gene will allow production of the specific immunological reagents necessary to characterize this molecule and study its role in the biology and pathogenesis of P. carinii. PMID- 8469117 TI - Cloning and identification of a two-component signal-transducing regulatory system from Bacteroides fragilis. AB - A DNA fragment was cloned from Bacteroides fragilis that bestowed low-level tetracycline resistance to Escherichia coli strains harbouring the cloned fragment on a multicopy plasmid. The tetracycline resistance determinant was localized to a 4.3kb Bg/II-PstI subfragment of the original clone. DNA sequence analysis of this fragment revealed that it contained an operon encoding two proteins: one of 519 amino acids, RprX, and a second of 236 amino acids, RprY. Protein sequence analysis revealed that the two proteins shared sequence identity with a family of multicomponent signal-transducing regulatory proteins identified from many diverse bacterial genera. RprX shared identity with the first component of the regulatory system, the histidine protein kinase receptor (for example EnvZ, PhoR, CheA, and VirA). RprY shared identity with the second member of the regulatory protein pair, the regulatory response protein (for example OmpR, PhoB, CheY, and VirG). Expression of these proteins from a multicopy plasmid vector in E. coli resulted in a decrease in the level of the outer membrane porin protein OmpF and an increase in the level of the outer membrane porin protein OmpC. The decrease in OmpF levels correlates with, and may be the cause of, the increased tetracycline resistance. Regulation of the levels of OmpF and OmpC is normally controlled by a multicomponent signal-transducing regulatory pair of proteins, EnvZ and OmpR. The effect RprX and RprY have on OmpF expression is mediated at the level of transcription. Thus, RprX and RprY may be interfering with the normal regulation of OmpF by OmpR and EnvZ. PMID- 8469118 TI - Mutagenesis of cellulase EGZ for studying the general protein secretory pathway in Erwinia chrysanthemi. AB - Extracellular secretion of endoglucanase Z (EGZ) from Erwinia chrysanthemi is mediated by the so-called Out general secretion pathway and, presumably, involves recognition of EGZ-carried structural information by one or more of the Out proteins. Investigating the relationships between structure and secretability of EGZ was the purpose of the present work. EGZ is made of two independent domains, located at the N- and C-proximal sides, separated by a Ser/Thr-rich region, which are responsible for catalysis and cellulose-binding, respectively. The existence of a secretion region ('targeting signal') was investigated by studying the secretability of modified EGZ derivatives. These resulted from deletion or peptide insertion and were designed by using the domain organization cited above as a guide. Catalytic and/or cellulose-binding tests showed that all proteins exhibited at least a functional EGZ domain while immunoblot analyses confirmed that neither the insertions nor the deletions led to grossly misfolded proteins. In contrast, all of the proteins lost their secretability in E. chrysanthemi. This suggested that at least two secretion motifs existed, one lying within each functional domain. The role of the Ser/Thr-rich linker region was subsequently tested. Accordingly, two proteins containing a linker region whose length was increased by the addition of 8 and 18 additional residues and one protein lacking the linker region were studied. All three exhibited endoglucanase activity and cellulose-binding ability, confirming the independence of the domains within the context of EGZ/polysaccharide interaction. In contrast, none was secreted by E. chrysanthemi.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469119 TI - TraM of plasmid R1 regulates its own expression. AB - Regulation of the traM gene, which encodes a factor essential for conjugation of resistance plasmid R1, was studied in vivo using translational gene fusion. traM"lacZ fusion constructs were transferred to the chromosome via the recombinant phage lambda RZ5. The level of beta-galactosidase expressed by the lysogens indicates that the traM promoters are very active. Expression of traM was diminished five- to sixfold when the single-copy plasmids R1 or R1-19 were present in trans. When recombinant plasmids carrying traM were present at higher copy numbers, traM expression was reduced as much as 45-fold. The negative effect of R1 plasmids on traM expression in trans, which we interpret as autoregulation, was observed regardless of whether the plasmids were conjugatively repressed or derepressed. Site-specific mutagenesis of the region encoding the N-terminus of the TraM protein eliminated the autoregulative effect indicating that the N terminal amino acids of the protein are important to its DNA-binding function. The autoregulatory behaviour of TraM is allele specific. R1- or P307-encoded TraM molecules were found to recognize only the cognate DNA. PMID- 8469120 TI - Characterization of a replicon of the moderately promiscuous plasmid, pGSH5000, with features of both the mini-replicon of pCU1 and the ori-2 of F. AB - The dominant, polA1-independent replicon of pGSH500, rep beta (1.8 kb), consists of a cis-acting oriV region of 245 bp; a repB gene that is essential for autonomous replication and 18, 30 to 36 bp iterons which constitute the inc/cop region. The molecular organization of rep beta resembles that of mini-pCU1 (IncN). Furthermore, there is a 58% identity between the Rep proteins of these replicons. RepB also shows a 31% identity with RepE of mini-F. In addition, an 80% identity over 200 bp was identified between the cis-acting beta oriV region and the equivalent region of ori-2 (mini-F). Replicons with deletions of repB could be complemented by Rep (pCU1) and RepE (mini-F) in trans, supporting the hypothesis that rep beta is a natural hybrid between a pCU1-like and F-like replicon. PMID- 8469121 TI - Short-term memory: where do we stand? AB - Two empirical challenges to the traditional "modal model" of short-term memory are that neither the Brown-Peterson distractor technique nor the recency effect in recall is well accommodated by that position. Additionally, the status of memory stores as such, has declined in response to proceduralist thinking. At the same time, the concept of coding, on which the modal model is silent, is increasingly central to memory theory. People need to remember things in the short term, but a dedicated store does not need to be the agency. PMID- 8469122 TI - The recency effect: implicit learning with explicit retrieval? AB - The recency effect in free recall features prominently in 1960s' theorizing about short-term memory, but has since been largely ignored. We argue that this stems from a preoccupation with the role of recency in the concept of primary memory and the neglect of its role in a broader working-memory framework. It is suggested that the recency effect reflects the application of an explicit retrieval strategy to the residue of implicit learning within a range of cognitive systems. When retrieved implicitly, the same residue is assumed to form the basis of priming effects. The various criteria for implicit learning described by Tulving and Schacter (1990) are successfully applied to the recency effect, and a retrieval process is outlined that can account for both long- and short-term recency effects. It is suggested that a framework combining recency, priming, and implicit learning provides a basis for understanding one of the most important features of cognition and memory, namely, that of maintaining orientation in time and place. PMID- 8469123 TI - Very short-term conceptual memory. AB - Short-term memory for conceptual information is largely missing from current models of short-term memory. Several phenomena are discussed that give evidence for very brief conceptual representations of stimuli. Although these fleeting representations do not surface readily with many of the standard methods for studying and testing short-term memory, I argue that they are fundamental to cognitive processing and to the form that long-term memory takes. PMID- 8469124 TI - Activation, attention, and short-term memory. AB - The premise of this paper is that the popular term "short-term memory" (STM) is vague because it is used to refer to either (1) the set of representations from long-term memory currently in a state of heightened activation or (2) the focus of attention or content of awareness. A more coherent conception of STM is hierarchical, with the focus of attention depicted as a subset of the activated portion of long-term memory. Research issues are discussed to illustrate that this simple conception of STM leads to testable predictions and useful lines of inquiry. PMID- 8469125 TI - A multinomial processing tree model for degradation and redintegration in immediate recall. AB - When items are presented for immediate recall, a verbal trace is formed and degrades quickly, becoming useless after about 2 sec. The span for items such as digits equals the number of items that can be pronounced in the available time. The length of the items affects span by affecting pronunciation rate. Other properties, such as phonological similarity and lexicality, can affect span without affecting pronunciation rate. These properties change the trace's useful lifetime by affecting redintegration. An analogy is drawn between trace reconstruction and repair of errors in speech. When a trace is degraded, one process attempts to form a phoneme string, and another process attempts to form a word. The two processes are autonomous and can be selectively influenced by lexicality and phonological similarity. The resulting processing tree models make simple predictions that depend on whether or not the influenced processes are sequential. The results are illustrated with data from experiments by Besner and Davelaar (1982). PMID- 8469126 TI - Short-term memory and sentence processing: evidence from neuropsychology. AB - Traditional models of memory assume that short-term memory, as measured by memory span, plays an important role in linguistic processing and the learning of verbal information. Contradicting this view are findings from a brain-damaged patient, E.A., who, despite a verbal memory span of about two items, demonstrated normal sentence comprehension in a variety of tasks. She was, however, impaired whenever verbatim phonological information had to be maintained or learned. These results and those from other patients with reduced span suggest that the phonological storage capacity that is critical to memory span plays only a limited role in language processing, specifically in the maintenance and learning of phonological forms. Implications for models of short-term memory are discussed. It is argued that short-term memory should be seen as deriving from the processing and retentive capacities of language processing modules, with span tasks drawing on only a subset of these modules. PMID- 8469127 TI - Varieties of working memory as seen in biology and in connectionist/control architectures. AB - Biological and computational concepts that underlie the nature of working memory are briefly reviewed. The conceptualization of working memory has changed dramatically in the last 30 years. Current biological work has monitored several aspects of memory, including activation decay, sustained activation, long-term connection change, and differential structures for episodic (hippocampal formation) and procedural learning. Current connectionist modeling has identified factors including multiple-region-based processing, control processing as well as data storage, tradeoffs between fast- and slow-connection-change learning effects, and the speeding of acquisition via multiple levels of learning. The need to relate the biological, behavioral, and computational constraints into models of working memory is discussed. Finally, conceptualizations of working memory must acknowledge the need for human learning systems to be robust enough to operate in a dynamic world. PMID- 8469128 TI - Short-term memory: a brief commentary. AB - Over the years, a metatheoretical view of short-term memory has developed. This view, closely related to the "modal" model from the 1960s, is supported by an increasing base of neurophysiological data, and a wide variety of empirical findings. It treats short-term memory as (1) the temporary, above threshold, activation of neural structures (related in not-too-well-specified ways to various recency effects); (2) a work space for carrying out virtually all cognitive operations involved in human cognition; and (3) the source of capacity limitations, accounting for certain memory limitations and most attentional limitations. The main problem with this view is the fact that it encompasses virtually everything that we are concerned with in human cognition--a successful model would almost be a general model of cognition, something the field has not yet approached. This situation is not grounds for despair. Progress is being made on many fronts, notwithstanding the fact that the most successful models are focused on specific task domains. Recent advances include an increasing awareness of the necessity for detailed models of short-term retrieval, a theme reflected in a number of articles in the present collection. PMID- 8469129 TI - Do we know what we've learned from listening to the news? AB - This study investigates the relationship between knowledge acquisition and an awareness of that knowledge within the context of listening to the news. Subjects listened to a recording of a radio news program consisting of regular news items as well as editorials, manipulated to be of high or low personal relevance. They then completed a surprise memory test and rated their confidence in their answers. In contrast to many studies, the results indicated a strong positive confidence-accuracy relationship. Confidence ratings were generally a better predictor of an individual's performance than were predictions based on item difficulty. Whereas subjects reported strong and accurate feelings of knowing, they apparently lacked complementary feelings of not knowing. The implications of these findings and others are discussed. PMID- 8469130 TI - Rhyme decisions to spoken words and nonwords. AB - Lexical effects in auditory rhyme-decision performance were examined in three experiments. Experiment 1 showed reliable lexical involvement: rhyme-monitoring responses to words were faster than rhyme-monitoring responses to nonwords; and decisions were faster in response to high-frequency as opposed to low-frequency words. Experiments 2 and 3 tested for lexical influences in the rejection of three types of nonrhyming item: words, nonwords with rhyming lexical neighbor (e.G., jop after the cue rob), and nonwords with no rhyming lexical neighbor (e.g., vop after rob). Words were rejected more rapidly than nonwords, and there were reliable differences in the speed and accuracy of rejection of the two types of nonword. The advantage for words over nonwords was replicated for positive rhyme decisions. However, there were no differences in the speed of acceptance, as rhymes, of the two types of nonword. The implications of these results for interactive and autonomous models of spoken word recognition are discussed. It is concluded that the differences in rejection of nonrhyming nonwords are due to the operation of a guessing strategy. PMID- 8469131 TI - The role of stimulus familiarity in context-dependent recognition. AB - Investigations of context-dependent recognition, a phenomenon in which recognition is better for items studied and tested with the same rather than different context, have shown serious inconsistencies. A simple organization of (1) contextual cues, distinguishing between local context (specific cues) and global context (general cues), and (2) stimulus familiarity, distinguishing between novel and familiar stimuli, reduces much of this variability. In two experiments, changes in both local context (descriptive label) and global context (environment) were manipulated in order to examine their effects on recognition memory for faces that differed in familiarity. Changes in local context impaired recognition of both unfamiliar and familiar faces; changes in environmental context impaired recognition only of unfamiliar faces. These results are consistent with the many failures to find impaired recognition of verbal stimuli under changed environmental contexts, and they suggest that stimulus familiarity is a critical parameter modulating environmental context effects. PMID- 8469132 TI - Processing novel compounds: evidence for interactive meaning activation of ambiguous nouns. AB - In three experiments, the meaning activation of ambiguous nouns in novel nominal compounds was investigated. Ambiguous nouns were unbalanced homographs occurring as the second members of the compound. Meaningful interpretations of the compounds were based on either the dominant or the subordinate meaning of the ambiguous noun. In Experiment 1, visually presented novel compounds serving as primes were followed at varying intervals by targets associatively related to distinct meanings of the ambiguous noun. In a lexical decision task, facilitation effects were found only for targets related to the meaning that was relevant for the interpretation of the compound. Experiment 2 showed that interactive activation could not be attributed to differences in semantic relatedness between the first members of compounds and targets. Experiment 3 demonstrated equal intralexical relatedness between members for both types of compounds. It is proposed that interactive activation may facilitate the interpretation of the novel compound. Compatible meaning aspects of the nouns may become more strongly activated, and incompatible meaning aspects may not become activated. The selection of meaning aspects relevant for interpretation would thereby be simplified. PMID- 8469133 TI - Neighborhood effects in visual word recognition: facilitatory or inhibitory? AB - In five experiments, in which subjects were to identify a target word as it was gradually clarified, we manipulated the target's frequency of occurrence in the language and its neighborhood size--the number of words that can be constructed from a target word by changing one letter, while preserving letter position. In Experiments 1-4, visual identification performance to screen-fragmented words was measured. In Experiments 1 and 2, we used the ascending method of limits, whereas Experiments 3 and 4 presented a fixed-level fragment. In Experiment 1, there was no relation between overall accuracy and neighborhood size for words between three and six letters in length. However, more errors of commission (guesses) were made for high-neighborhood words and more errors of omission (blanks) were made for low-neighborhood words. Letter errors within guesses occurred at serial positions having many neighbors, and these positions were also likely to contain consonants rather than vowels. In Experiment 2, a small facilitatory effect of neighborhood size on both high- and low-frequency words was found. In contrast, in Experiments 3 and 4, using the same set of words, inhibitory effects of neighborhood size, but only for low-frequency words, were found. Experiment 5, using a speeded identification task, showed results parallel to those of Experiments 3 and 4. We suggest that whether neighborhood effects are facilitatory or inhibitory depends on whether feedback allows subjects to disconfirm initial hypotheses that the target is a high-frequency neighbor. PMID- 8469134 TI - Infants' eyewitness testimony: effects of postevent information on a prior memory representation. AB - In eyewitness testimony research, postevent information impairs retention of the original event and increases the probability that interpolated information will be identified as part of the original event. The present experiments studied these effects with 3-month-olds. Infants learned to kick to move a particular crib mobile and then were briefly exposed to information about a novel mobile. The novel postevent information impaired recognition of the original mobile when it immediately followed training but not when it was delayed by 1 day. Like adults, infants treated the postevent information as part of the original training event, continuing to do so for at least 2 weeks. We propose that postevent information displaces conflicting information coactive with it in primary memory and creates a new, updated memory token of the event. Once the new token leaves primary memory, however, it is protected; only a copy can be retrieved and modified in the future. PMID- 8469135 TI - Analysis of carotenoids in human and animal tissues. PMID- 8469136 TI - Plasma carotenoid levels in anorexia nervosa and in obese patients. PMID- 8469137 TI - Psoralen photosensitization and plasma and cutaneous beta-carotene concentrations in hairless mice. PMID- 8469138 TI - Human metabolism of carotenoid analogs and apocarotenoids. PMID- 8469139 TI - Assay for carotenoid 15,15'-dioxygenase in homogenates of rat intestinal mucosal scrapings and application to normal and vitamin A-deficient rats. PMID- 8469140 TI - Evaluation of carotenoid intake. PMID- 8469141 TI - Retinoic acid synthesis from beta-carotene in vitro. PMID- 8469142 TI - Uptake and cleavage of beta-carotene by cultures of rat small intestinal cells and human lung fibroblasts. PMID- 8469143 TI - Enzymatic conversion of all-trans-beta-carotene to retinal. AB - Enzymatic conversion of all-trans-beta-carotene to retinal by a partially purified enzyme from rabbit, rat, and human neonatal intestinal mucosa has been demonstrated. The enzymatic product was characterized based on the following evidence. First, the product gave rise to its O-ethyl oxime by treatment with O ethylhydroxylamine with an absorption maximum at 363 nm in ethanol characteristic of authentic retinal (O-ethyl) oxime. High-performance liquid chromatography of this derivative yielded a sharp peak with a retention time of 7.99 min, corresponding to the authentic compound. The enzyme blank and boiled enzyme blank failed to show any significant HPLC peaks corresponding to retinal (O-ethyl) oxime or retinal or retinol. Second, the mass spectrum of the O-ethyl oxime of the enzymatic product was identical to that of authentic retinal (O-ethyl) oxime (m/z 327, 45%; m+ and m/z 282, 100%, methoxy). Third, the 14C radioactivity persisted to constant specific activity even after repeated crystallization of the retinal (O-ethyl) oxime isolated from the enzyme reaction with purified beta [14C]carotene. Fourth, the enzymatic product exhibited an absorption maximum at 370 nm in light petroleum characteristic of authentic retinal. Furthermore, it was reduced by horse liver alcohol dehydrogenase to retinol with an absorption maximum at 326 nm in light petroleum. This retinol was enzymatically esterified to retinyl palmitate by rat pancreatic esterase with a retention time of 10 min on HPLC, corresponding to authentic retinyl palmitate. Thus, the enzymatic product of beta-carotene cleavage by the partially purified intestinal enzyme has been unequivocally confirmed to be retinal. Similarly, enzymatic conversion of all-trans-beta-carotene to retinal by an intestinal mucosal enzyme from autopsy samples of human neonates has also been demonstrated. Based on the observed activities among intestinal samples from 12 premature infants, the BCC enzyme activity ranged from 3.3 to 1210 pmol/mg mucosal protein/hr. However, the observed activities in the human autopsy samples may be markedly underestimated, presumably because of marked loss of enzyme activity from the time of death to the time of assay. Therefore, the true activity of the enzyme can be assessed only after the extent of the loss of its activity on storage of the human samples can be accurately measured. Nonetheless, the demonstration of BCC enzyme activity in human neonates shows that beta-carotene may be an important source of vitamin A nutrition during gestation. PMID- 8469144 TI - Evolutionary conservation and structural similarities of carotenoid biosynthesis gene products from photosynthetic and nonphotosynthetic organisms. PMID- 8469145 TI - Carotenoid absorption in humans. PMID- 8469146 TI - Protection by cloned carotenoid genes expressed in Escherichia coli against phototoxic molecules activated by near-ultraviolet light. PMID- 8469147 TI - Association of carotenoids with human plasma lipoproteins. PMID- 8469148 TI - Carotenoid analysis in mutants from Escherichia coli transformed with carotenogenic gene cluster and Scenedesmus obliquus mutant C-6D. PMID- 8469149 TI - Functional analysis and purification of enzymes for carotenoid biosynthesis expressed in photosynthetic bacteria. PMID- 8469150 TI - Characteristics of membrane-associated carotenoid-binding proteins in cyanobacteria and prochlorophytes. PMID- 8469151 TI - Photoregulated carotenoid biosynthetic genes of Neurospora crassa. PMID- 8469152 TI - Solubilization, cellular uptake, and activity of beta-carotene and other carotenoids as inhibitors of neoplastic transformation in cultured cells. PMID- 8469153 TI - Differentiation between central and excentric cleavage of beta-carotene. PMID- 8469154 TI - Carotenoid-protein complexes. AB - This chapter provides an updated report of carotenoprotein-related research. Very few carotenoproteins have been purified; however, their presence in aqueous extracts may be indicated by spectroscopic evidence. Carotenoproteins have been isolated, purified, and characterized from the ectoderm, exoskeleton, eggs, and ovaries of marine invertebrates, especially crustaceans. Water-soluble and detergent-soluble carotenoid-protein complexes have also been isolated from the cytoplasmic membrane of some cyanobacteria, Mangifera indica, and carrots. Recently, we have been able to partially purify a beta-carotene-protein complex from fresh livers of rats fed beta-carotene. Studies are currently in progress to purify and characterize the protein. This is the first successful isolation of a vertebrate carotenoprotein. The isolation of carotenoproteins is generally by standard techniques of protein chemistry. Purification, crystallization of the complex, and reconstitution of apoprotein and carotenoid components have been achieved for some crustacean carotenoproteins. The complex is very sensitive to bright light and to temperatures above that of refrigeration. However, it is best preserved in solutions of high ionic strength or as a precipitate in strong ammonium sulfate solutions. PMID- 8469155 TI - Analysis of carotenoids in human plasma and tissues. AB - Procedures are described for the extraction and analysis of carotenoid pigments from human tissues and plasma. The method allows resolution of many polar pigments, including several such compounds more polar than zeaxanthin. While the method requires two separate HPLC runs when applied to tissues containing significant quantities of triglyceride, the additional information made available on the polar carotenoid composition of such samples is substantial. PMID- 8469156 TI - Assessing variability in quantitation of carotenoids in human plasma: variance component model. PMID- 8469157 TI - Philosophies for the design and development of clinical decision-support systems. AB - Little significance is attached by medical informatics workers to the many practical issues which affect the development of clinical decision-support systems. We examine the current state of research in clinical decision-support, the characteristics and motivations of developers, and the perceptions of intended end-users. Factors which adversely affect the success of systems are highlighted and pointers to good practice discussed. We then propose a coherent approach to system development, consisting of requirements analysis, software design, implementation, testing, evaluation and maintenance. PMID- 8469158 TI - Graphical access to medical expert systems: IV. Experiments to determine the role of spoken input. AB - The goal of our research is to design improved interfaces for medical expert systems. Previously, the use of graphical techniques was explored to improve the acceptance by clinicians of the user interface. Now that devices that accept spoken input are available, we wish to design interfaces that take advantage of this potentially more natural modality for interaction. To understand how clinicians might want to speak to a medical decision-support system, we carried out an experiment that simulated the availability of a spoken interface to the ONCOCIN medical expert system. ONCOCIN provides therapy advice for patients on complex cancer therapy protocols based on a description of the patient's current medical status and laboratory-test values. In the experiment, we had oncologists present a clinical case while observing the ONCOCIN flowsheet display. A project member listened to the presentation and filled in values for the flowsheet, as well as introducing purposeful misunderstandings of the input. The results suggest that each individual developed a stereotypical grammar for communicating with the program. Our experience with the purposeful miscommunications suggests particular ways to tailor requests for repetition based on the part of the utterance that was not understood. PMID- 8469159 TI - Graphical access to medical expert systems: V. Integration with continuous-speech recognition. AB - This paper describes three prototypes of computer-based clinical record-keeping tools that use a combination of window-based graphics and continuous speech in their user interfaces. Although many of today's commercial speech-recognition products achieve high rates of accuracy for large grammars (vocabularies of words or collections of sentences and phrases), they can only "listen for" (and therefore recognize) a limited number of words or phrases at a time. When a speech application requires a grammar whose size exceeds a speech-recognition product's limits, the application designer must partition the large grammar into several smaller ones and develop control mechanisms that permit users to select the grammar that contains the words or phrases they wish to utter. Furthermore, the user interfaces they design must provide feedback mechanisms that show users the scope of the selected grammars. The three prototypes described were designed to explore the use of window-based graphics as control and feedback mechanisms for continuous-speech recognition in medical applications. Our experiments indicate that window-based graphics can be effectively used to provide control and feedback for certain classes of speech applications, but they suggest that the techniques we describe will not suffice for applications whose grammars are very complex. PMID- 8469160 TI - Developmental toxicity risk assessment: a rough sets approach. AB - A rough-sets approach was applied to a data set consisting of animal study results and other compound characteristics to generate local and global (certain/possible) sets of rules for prediction of developmental toxicity in human subjects. A modified version of the rough-sets approach is proposed to allow the construction of an approximate set of rules to use for prediction in a manner similar to that of discriminant analysis. The modified rough-sets approach is superior in predictability to the original form of rough-sets methodology. In comparison to discriminant analysis, modified rough sets (approximate rules) appear to be better in overall classification, sensitivity, positive and negative predictive values. The findings were supported by applying the modified rough sets and discriminant analysis on a test data set generated from the original data set by using a resampling plan. PMID- 8469161 TI - A genetic algorithm to improve a neural network to predict a patient's response to warfarin. AB - The ability of neural networks to predict the international normalised ratio (INR) for patients treated with Warfarin was investigated. Neural networks were obtained by using all the predictor variables in the neural network, or by using a genetic algorithm to select an optimal subset of predictor variables in a neural network. The use of a genetic algorithm gave a marked and significant improvement in the prediction of the INR in two of the three cases investigated. The mean error in these cases, typically, reduced from 1.02 +/- 0.29 to 0.28 +/- 0.25 (paired t-test, t = -4.71, p < 0.001, n = 30). The use of a genetic algorithm with Warfarin data offers a significant enhancement of the predictive ability of a neural network with Warfarin data, identifies significant predictor variables, reduces the size of the neural network and thus the speed at which the reduced network can be trained, and reduces the sensitivity of a network to over training. PMID- 8469162 TI - A new method to assess the difficulty of a medical diagnosis: application to electrocardiographic interpretation. AB - A new method to assess the relative difficulty of a medical diagnosis and the efficacy of a diagnostic procedure is described. The cases within a population are classified by N independent interpreters, i.e., medical experts or computer programs. The percentages of correctly diagnosed cases by N (unanimity), N-1, N 2, ..., zero interpreters, respectively, are calculated. These N + 1 percentages are presented in a histogram. A cumulative plot is derived from the "unanimity" value. The ratio "unanimity value"/"zero value" is proposed as an index of diagnostic performance. An application to the CSE database is presented which is composed of 1,220 electrocardiographic tracings interpreted by 13 cardiologists and 15 computer programs. The cumulative plots, the performance index and Log (index) values, established for eight different diagnostic statements, clearly show the relative degree of diagnostic difficulty for each of them and the particular efficacy of each approach, i.e., electrocardiography versus vectorcardiography, and computerized versus human interpretation. PMID- 8469163 TI - Semantic analysis of medical records. AB - A program (LogStory) is described that was developed for the automatic semantic analysis of clinical narratives, stored in a computerized problem-oriented medical record (PROMED). The diagnoses were written in a free-text format during consultation, and later collected into diagnostic classes, e.g., diseases. A lexical parser automatically created dictionaries from the clinical narrative associated with each disease. Automatic (fuzzy) set operations were performed on the words associated with each class. The manifestations of 16 diseases were automatically extracted by pairwise operations on the word sets. The correlation between diseases and corresponding signs, symptoms and treatment was highly significant (p < 0.001). Applying the difference operation on diseases with disjunct sets of clinical findings allowed the recovery of disease-specific knowledge. The evolution of a disease was accounted for, and the system was able to generalize its findings. The PROMED-LogStory concept enables the processing of natural language and may be a powerful tool for knowledge acquisition and clinical research. PMID- 8469164 TI - Information exchange in a patient-physician encounter. A quantitative approach. AB - The efficiency of data acquisition in a patient-physician encounter was investigated. In a simulation study, in which 60 family physicians and eight internists participated, the patient was replaced by an actor who used a structured set of patient data. The simulation model proved to be quite natural; data acquisition was primarily influenced by the amount of time available. Discerning between overall and diagnostic information, conclusions could be drawn on the effectiveness of data acquisition. Under time pressure, physicians tend to look for broadly defined symptoms rather than for details of the patient's illness. The collection of patient data then has an inquisitive character, having implications for the quality of clinical judgement. The physician's capabilities in eliciting relevant information from a patient appear to be of crucial importance for clinical problem-solving. The present study shows that patient physician interviewing is effective insofar it concerns broad descriptions, but ineffective in eliciting specific data. If interviewing is laborious and time consuming this may, therefore, affect the kind of information to be collected. PMID- 8469165 TI - Modelling in-patient bed usage behaviour in a department of geriatric medicine. AB - The flow of patients through geriatric hospitals has been previously described in terms of acute and long-stay states where the bed occupancy at a census point is modelled by a mixed exponential model. Using data for sixteen years the model was fitted to successive annual census points, in order to provide a description of temporal trends. While the number of acute patients has remained fairly stable during the period, the model shows that there has been a decrease in the number of long-stay patients. Mean lengths of stay in our geriatric hospital before death or discharge have decreased during the study period for both acute and long stay patients. Using these fits of the mixed exponential model to census data, a method is provided for predicting future turnover of patients. These predictions are reasonably good, except when the turnover patterns go through a period of flux in which assumption of stability no longer holds. Overall, a methodology is presented which relates census analysis to the behaviour of admission cohorts, thus producing a means of predicting future behaviour of patients and identifying where there is a change in patterns. PMID- 8469166 TI - MultiLink--an intermediary system for multi-database access. AB - The design and implementation is described of MultiLink, a desktop system for direct enduser access to remote bibliographic information. The system is an application of a client-server technique based on a campuswide network, with the objective to assist end-users to accomplish the information--retrieval process by capturing knowledge and expertise for searches in query formulations. MultiLink, via intelligent interfaces, allows users to access several dozens of bibliographic databases. The application integrates regional, national and international resources, and brings library services to the user's desktop level. PMID- 8469167 TI - HTLV-1 sequences in lymphocytes of a patient with non-tropical spastic tetraparesis and her asymptomatic husband. AB - We describe a 65-year-old woman born and living in Northern Italy affected by non tropical spastic tetraparesis and her asymptomatic husband presenting HTLV-1 sequences in their lymphocytes detected by polymerase chain reaction (PCR). We discuss the significance of the case and the mechanism involved in HTLV-1 infection and the relationship with neurological disorders, stressing that this case is the first reported in Italy. PMID- 8469168 TI - Preliminary data on the establishment of permanent cell lines continuously producing HIV-1: factors affecting the transmissibility and adaptability of "wild" HIV-1 isolates. AB - This study examines some technical aspects of the transmission to and permanent adaptability in continuous cell lines of wild HIV-1 isolates. Three cell systems (the lymphocytic cell lines Molt-3 and H-9 and the monocytoid cell line U-937) and two transmission protocols (cell to cell and cell-free) were used. Two different replicative behaviours were observed among isolates efficiently transmitted: a) transmissibility but not adaptability (consisting in a limited length of viral replication); aa) transmissibility and adaptability (consisting in a stable and long term virus production). The second type of replication was confined to viruses from patients with severe immunodeficiency. Technical and viral factors can affect the rate of transmissibility and adaptability: the modality of infection (cell to cell transmission appeared to be the most efficient) and the tropism of the virus (some viruses could infect only one T cell line). PMID- 8469169 TI - The elevation of circulating platelets after IFN-alpha therapy in HIV-1 seropositive thrombocytopenic patients correlates with increased plasma levels of IL-6. AB - In this study we evaluated the effect of recombinant interferon-alpha 2b (IFN alpha 2b) therapy on the number of circulating platelets and interleukin-6 (IL-6) plasma levels in 12 human immunodeficiency virus type 1 (HIV-1) seropositive patients, affected by a severe and persistent thrombocytopenia. The levels of IL 6 in plasma of HIV-1 seropositive thrombocytopenic subjects before IFN-alpha therapy were similar (80 +/- 15 pg/ml) to those observed in 15 HIV-1 seropositive asymptomatic individuals (75 +/- 12 pg/ml) and 30 HIV-1 seronegative blood donors (59.5 +/- 25 pg/ml). On the other hand, IL-6 amounts (148 +/- 36 pg/ml) in plasma of HIV-1 seropositive thrombocytopenic subjects were significantly (p < 0.01) increased after 5 weeks of IFN-alpha 2b therapy, showing a good correlation (p < 0.05, chi-square test) with the levels of circulating platelets. Moreover, an increased spontaneous IL-6 production by peripheral blood monocytes was observed after IFN-alpha 2b therapy in HIV-1 seropositive thrombocytopenic patients. Our results suggest that an increased production of IL-6, one of the main factors controlling thrombocytopoiesis, may partially explain the ability of IFN-alpha 2b therapy, to restore platelet production in a subset of HIV-1 seropositive thrombocytopenic individuals. PMID- 8469171 TI - Molecular characterization of Yersinia strains isolated from human and environmental sources. AB - Thirty-seven strains of Yersinia isolated from human and environmental sources were investigated for virulence and molecular characteristics. Clinical isolates of Y. enterocolitica serotypes 0:3 and 0:9, harbouring the 45 MDa virulence plasmid were Ca++ dependent and responded positively to the CV-binding assay. The environmental Y. kristensenii strain, although harbouring a 45 MDa plasmid proved to be negative for both assays. All the environmental strains showed pyrazinamidase activity, while isolates from human sources proved negative. Two different plasmid profiles were disclosed: one Y. enterocolitica strain (serotype 0:7, 8) showed one plasmid of 67 MDa and one plasmid of 1.5 MDa. Eleven human isolates of Y. enterocolitica and one environmental strain of Y. krinstensenii showed only one plasmid of 45 MDa. Restriction endonuclease analysis of the 45 MDa plasmids supported the hypothesis that the environmental Y. krinstensenii plasmid is unrelated to the family of homologous virulence plasmids of Y. enterocolitica. PMID- 8469170 TI - Adherence of Borrelia burgdorferi and Borrelia hermsii to mammalian cells in vitro. AB - This study investigated the ability of Borrelia burgdorferi and Borrelia hermsii to attach the surface of several types of in vitro-cultured mammalian cells. Borreliae showed different adhesion efficiencies depending on cell type and temperature. Temperatures both lower and higher than 33 degrees and 37 degrees C respectively, decreased the adhesion of borreliae which preferentially adhere to human fibroblast-like cells. The adhesion process, mediated by structures exposed onto the surface of the microorganisms, also proved to be sensitive to the treatment of mammalian cells with hyaluronidase and sialidase, confirming that carbohydrate receptors are involved in the adhesion of borreliae to eukaryotic cells. PMID- 8469172 TI - Non-transmissible and self-transmissible plasmids conferring drug resistance in clinical isolates of Serratia marcescens from hospitals in Riyadh, Saudi Arabia. AB - Sixty Serratia marcescens isolates were obtained from patient specimens from three different hospitals in the city of Riyadh. These were tested for their antibiotic resistance factors using eleven different antibiotics. Their ability to transfer antibiotic resistance plasmids to a sensitive E. coli strain (RR1) was tested by transformation and conjugation experiments. Agarose gel electrophoresis was used to determine the size and number of the R-plasmids. Southern blotting was used to assess homologies between antibiotic resistance plasmids from different isolates. Among the isolates tested, 36.7% contained plasmids, and all these were from strains isolated from two hospitals. No R plasmids could be detected among the multiple resistant strains isolated from the third hospital. Among the strains that contained plasmids, approximately 63.6% transferred multiple antibiotic resistance to E. coli and the rest transferred only one antibiotic resistance marker. The majority of strains carrying out the plasmids showed similarities in band number and size. In view of the similarities this group was denoted the predominant group, and selected for further molecular investigations. Restriction endonuclease digests of plasmids from this group gave the same restriction pattern which confirmed that they were closely related. Hybridization experiments using these plasmids and nick-translated 32p-labelled pBR-322 DNA probe, showed that all the large bands (36 kb) are related and exhibit homology with pBR-322. PMID- 8469173 TI - Inactivation of ribosomes by an inhibitor of protein synthesis from Salmonella enteritidis. AB - Sonic extracts of Salmonella enteritidis contain a factor which inhibits protein synthesis in cell-free systems by irreversibly inactivating ribosomes. The extent of the inactivation of ribosomes depends on the system used to assay protein synthesis, natural mRNA translation being more strongly inhibited than poly(U) translation. The inhibitory power of the Salmonella factor is destroyed by trypsin and by 5% mercaptoethanol. Placental RNase inhibitor is unable to protect ribosomes from inactivation. PMID- 8469174 TI - Human intestinal methanogens and lactulose administration. AB - The effect of lactulose on human intestinal methanogenic bacteria in ten subjects on lactulose therapy and ten control adults was evaluated. Methanogens were found in 90% of the population examined (9 treated subjects and 9 controls). A marked variability in methanogen number (ranging from 10(3)-10(10)/gdw) was observed in lactulose-treated subjects and in controls. Analysis of variance showed no significant difference between the two groups. PMID- 8469175 TI - Rapid differentiation of untreated, autoclaved and ozone-treated Cryptosporidium parvum oocysts using dielectrophoresis. AB - A novel automated dielectrophoretic electrode apparatus and procedure was used to differentiate between untreated, autoclaved and ozone treated Cryptosporidium parvum oocysts recovered from water. A freeze-frame video technique enabled images of oocysts to be captured when they collected at sites above and between the electrodes upon application of an electric field. The number of oocysts collecting could then be conveniently counted. Varying the frequency of the applied electric field allowed the construction of characteristic spectra for each sample. PMID- 8469176 TI - Antifungal activity of Myxococcus species 1 production, physicochemical and biological properties of antibiotics from Myxococcus fulvus S110 (Myxobacterales). AB - Chloroform extracts of the culture supernatant of a strain of Myxococcus fulvus isolated from soil were fungistatic and prevented germination of spores of Botrytis cinerea. The antibiotics were produced during the exponential phase of growth and the effects of altering medium composition are described. The activity was fractionated into neutral, acidic and basic fractions. The neutral fraction had a molecular weight of 244 and was tentatively identified as 11-phenyl undecadiene-2-ol. The acidic fraction was primarily n-hexadecanoic acid. The basic fraction contained components [N-(2-phenylethyl)-acetamide, and compounds tentatively identified as 1-isoquinoline carbonitrile and substituted quinolines] which have not previously been described in the myxobacteria. PMID- 8469177 TI - The distribution and properties of some hydrolytic enzymes from Porphyromonas gingivalis W50. AB - The production, distribution (as cell-bound, extracellular or associated with vesicles) and properties of four hydrolytic enzymes from Porphyromonas gingivalis were studied. During batch culture, enzymes appeared as cell bound until 72 h when extracellular trypsin-like protease and glycylprolyl dipeptidase were found. Alkaline phosphatase and N-acetyl-beta-glucosaminidase continued to be mainly cell-bound until 96 and 144 h post-inoculation, respectively. The pH optima for trypsin-like protease and dipeptidase activities were 7.5 and 8.0, respectively. Activity was most stable between pH 6.5 and 9.0 for the trypsin-like protease and pH 8.0 for dipeptidase. For phosphatase and N-acetyl-beta-glucosaminidase, double peaks of activity occurred at pH 8.0, 10.5 and 6.5, 7.5, respectively. Phosphatase was most stable at pH 7.0, whilst N-acetyl-beta-glucosaminidase was stable over a wide range of pH from 5.0-10.0. Molecular weight estimation by gel filtration gave 170 and 65 kD for trypsin-like protease, 200 and 24 kD for glycylprolyl dipeptidase, 125 and 24 kD for phosphatase, and 22 kD for N-acetyl beta-glucosaminidase. PMID- 8469178 TI - Glucose uptake in the yeast Saccharomyces cerevisiae. AB - The glucose uptake of Saccharomyces cerevisiae cells in sporulation medium for 3 h was higher than that of cells in 5.5 mM glucose medium. This difference might be due to the change in cell structure which is necessary for the sporulation process. In both types of cells, the glucose uptake activity became higher as the glucose concentration of the medium decreased. PMID- 8469179 TI - Different immunomodulator regulated patterns of effector-target cell interactions: a novel application of microcalorimetry. AB - Microcalorimetric studies of target/effector cell interactions are reported. Significant changes in the observed thermal profiles are seen upon pre-incubation of the effector cells with chemical immunomodulators. The results of these latter studies indicate that the microcalorimetric technique can reveal differences in the modes of action of different groups of immunomodulators. It is proposed that the technique can be used to screen drug activities and, following further analytical work, to contribute to an understanding of modes of action. PMID- 8469181 TI - 1993 MSMS Directory Issue. PMID- 8469180 TI - Identification and growth characteristics of pink pigmented oxidative bacteria, Methylobacterium mesophilicum and biovars isolated from chlorinated and raw water supplies. AB - Pink pigmented bacteria were isolated from a blood bank water purification unit, a municipal town water supply (tap water), and an island (untreated) ground water source. A total of thirteen strains including two reference strains of pink pigmented bacteria were compared in a numerical phenotypic study using 119 binary characters. Three clusters were derived, one major cluster of eleven strains was subdivided into two sub-clusters on the basis of methanol utilization. Five strains were facultative methylotrophs and were classified as Methylobacterium mesophilicum biovar 1. The other six strains did not utilize methanol, but on the basis of high phenotypic similarity of 83.6% were classified as M. mesophilicum biovar 2. The single reference strain comprising cluster 2 Pseudomonas extorquens NCIB 9399 was assigned to the genus Methylobacterium and classified as M. extorquens. Cluster 3 was the single reference strain Rhizobium CB 376. PMID- 8469182 TI - Effective care in midwifery: research, the professions and the public. PMID- 8469183 TI - Appropriate midwifery care for the 1990s. Midwifery practice: where we came from- where we can go. PMID- 8469184 TI - Giving complementary therapy with midwifery care for the 1990s. PMID- 8469185 TI - 1990s: commitment to change. PMID- 8469186 TI - The team approach to giving midwifery care for the 1990s. PMID- 8469187 TI - Carbon monoxide poisoning: from old dogma to new uncertainties. PMID- 8469188 TI - Electrical neurostimulation for angina pectoris. Acupuncture and TENS--where east meets west. PMID- 8469189 TI - Perspectives on tropical health. PMID- 8469190 TI - Medical ethics--past and future. PMID- 8469192 TI - Homosexually acquired gonorrhoea in Victoria, 1983-1991. AB - OBJECTIVE: To identify trends in the rate of gonorrhoea, particularly homosexually acquired infection. DESIGN: A retrospective descriptive study of records stored in a relational database. Records contain epidemiological, demographic and microbiological data of laboratory confirmed cases of gonorrhoea. SUBJECTS: Individuals with gonorrhoea diagnosed microbiologically in Victoria and from whom isolates were subsequently forwarded to the Microbiological Diagnostic Unit, University of Melbourne, for further bacteriological work for the years 1983-1991. RESULTS: Overall, gonorrhoea is declining in Victoria in the general population but has risen sharply in recent years in homosexually active men. An increased number of cases of rectal gonorrhoea in men has also been noted. An age cohort effect in homosexually active men is only evident for the final year of the study. These men do not tend to acquire gonorrhoea abroad and beta-lactamase producing gonococci are rarely found in this group. CONCLUSIONS: Gonorrhoea in homosexually active men has increased disproportionately to the rate of infection in heterosexual men in recent years, despite intensive education and counselling aimed at the gay community. Implications for risk of acquisition of other sexually transmitted diseases, including the human immunodeficiency virus, are evident. PMID- 8469191 TI - Recent military experience with malaria chemoprophylaxis. AB - OBJECTIVE: To assess the value of various drug regimens for malaria prophylaxis under circumstances where dapsone and pyrimethamine (combined as Maloprim) and chloroquine, followed by the 14-day primaquine eradication course, were no longer effective in protecting military personnel against falciparum and vivax malaria. DESIGN, SETTING AND PARTICIPANTS: Various drug regimens given to four groups of healthy male members of the Australian Army during training exercises in malarious countries. INTERVENTIONS: Four groups of soldiers were given different regimens for 3-12 weeks: Group 1--mefloquine (250 mg weekly); Group 2- doxycycline (100 mg daily); Group 3--doxycycline (100 mg daily) and primaquine (7.5 mg daily); and Group 4--doxycycline (50 mg daily) and chloroquine (300 mg weekly). Except in Group 3, each of these regimens was followed by a 7.5 mg dose of primaquine three times a day for two weeks. MAIN OUTCOME MEASURES: The proportion of participants in the various prophylactic drug groups who developed falciparum or vivax malaria during or after the intervention. RESULTS: Group 1: 40 men receiving mefloquine were all protected against falciparum malaria but four (10%) developed vivax malaria. These results were not statistically different from those obtained for either falciparum (P = 0.28) or vivax (P = 0.36) malaria in the control group of 64 men receiving Maloprim and chloroquine. Group 2: 60 men receiving doxycycline (no control group) were all protected against falciparum malaria but two developed vivax malaria. Group 3: 124 men, of whom 55 received doxycycline and 69 primaquine in addition to doxycycline, were all protected against falciparum malaria. However, 13 men taking only doxycycline developed vivax malaria two to three weeks after prophylaxis, whereas no vivax infections were observed in the men taking the drug combination (P = 0.0001). Group 4: no malaria infections were observed in 125 men receiving doxycycline and chloroquine for 13 weeks, probably because of the low prevalence of malaria in the training area. CONCLUSIONS: These studies confirm that doxycycline is very effective in preventing falciparum malaria and, for the first time, also suggest that doxycycline used in combination with small doses of primaquine may prevent (not only suppress) vivax malaria. If further studies confirm these findings, the use of such a drug combination would reduce the incidence of both vivax and falciparum malaria in returning travellers. For individuals with a high risk of exposure to malaria, it would also forestall the need to take the bothersome primaquine eradication course. PMID- 8469193 TI - Short and medium term outcomes after rollerball endometrial ablation for menorrhagia. AB - OBJECTIVE: To review prospectively the intraoperative, short and medium term outcomes of patients treated by rollerball endometrial ablation during the learning curve for this relatively new procedure. PATIENTS AND TECHNIQUES: Seventy-seven women with menorrhagia (71 with dysfunctional bleeding; six with additional small intramural myomas) underwent hysteroscopic rollerball endometrial ablation by coagulation diathermy during 1.5% glycine irrigation, after a two-month period of hormonal suppression. OPERATIVE AND SHORT-TERM EFFECTS: These were recorded at operation and six-week follow-up. No serious short-term complications were recorded. Objective measurement of intraoperative blood loss was always less than 20 mL. One woman experienced uterine perforation with a narrow cervical dilator which did not interfere with the ablation, and two patients had mild postoperative uterine infections. One patient experienced persistent postoperative pain. MEDIUM-TERM OUTCOME: This was recorded at each visit, or by telephone, and confirmed by questionnaire at one year. Twenty-five per cent achieved complete amenorrhoea, 29% staining only, 30% light periods, 10% "normal" or erratic periods and 6% were unchanged. Five patients underwent a second ablation, and three of these later underwent hysterectomy. Measured menstrual blood loss fell from 104 +/- 19 mL (mean +/- standard error of mean) to 1.7 +/- 1.1 mL at six months in 18 women. Other menstrual symptoms were also often dramatically reduced. Of those women with dysmenorrhoea, 33% were cured and 43% markedly improved; of those with midcycle pain, 28% were cured and 53% markedly improved; of those with significant premenstrual symptoms, 13% were cured, 47% markedly improved, 11% unchanged, and 6% were worse. CONCLUSIONS: This new procedure is a safe and effective treatment for menorrhagia caused by dysfunctional uterine bleeding, with impressive ancillary benefits for dysmenorrhoea, midcycle pain and premenstrual tension. It is often called minimally invasive surgery, but it must be recognised that it is not minor surgery. PMID- 8469194 TI - Percutaneous ultrasound guided uterine needle biopsy. AB - OBJECTIVE: To determine the safety, accuracy and usefulness of percutaneous ultrasound guided uterine needle biopsy. SETTING: Transabdominal uterine biopsy was performed with an ultrasound directed biopsy gun. The biopsy was performed as an outpatient procedure under local anaesthesia. MAIN OUTCOME MEASURES: The safety, accuracy and clinical value of the procedure; a comparison of the clinical and ultrasound diagnoses with the biopsy and surgical histological diagnoses; and the effect of the biopsy result on the choice of treatment by the surgeon and patient. RESULTS: There were no complications. Accuracy was validated in all seven patients who subsequently had surgical procedures and more extensive myometrial histological investigation. Biopsy diagnosis improved clinical diagnosis in nine of the ten patients, and altered or assisted in the ultrasound diagnosis in eight of the ten patients. Decisions concerning choice of treatment by the doctor or patient were assisted by the biopsy result in seven patients. CONCLUSION: Percutaneous ultrasound guided uterine needle biopsy is a useful procedure in the diagnosis of myometrial disease. PMID- 8469196 TI - The burden of tropical diseases. AB - More than half the world's population is at risk of the tropical diseases malaria, leprosy, schistosomiasis, lymphatic filariasis, onchocerciasis, Chagas disease, African trypanosomiasis and leishmaniasis, and half a billion people are infected with at least one of these diseases. We present statistic on the population at risk and the infected population, and on the major morbidity and mortality attributable to each of these diseases. During the next decade the prevalence of leprosy, Chagas disease, and onchocerciasis is expected to fall, but for the other tropical diseases the epidemiological situation may remain stagnant or even worsen. PMID- 8469195 TI - Medical ethics--fact or fiction? AB - In recent times the ethical behaviour of doctors has come under close scrutiny with some unhappy consequences. During the millennia in which medicine has been practised much has been written about ethics and nowadays there is no shortage of codes and declarations and of ethics committees to tell us what to do. These events raise questions about the status of the general principles of ethics and of the significance of particular assertions in that field. There is also the important question of whether or not there has been, or is, any connection at all between utterances about medical ethics and the behaviour of the members of our profession. I believe that the ethical problems confronting doctors are becoming more complex, and give my two rules of thumb for proper behaviour. PMID- 8469197 TI - Superficial mycoses: a practical approach. PMID- 8469198 TI - Superficial mycoses: a strategic approach. PMID- 8469199 TI - Management of chronic pain. AB - The principles of chronic pain management in the elderly are the same as in younger people; whenever possible, the cause of the pain should be identified and eradicated. However, older people are more likely to suffer pain from incurable conditions, and the emotional component of the suffering may be considerable. Treatment options include analgesics, opiates, antidepressants and anticonvulsants as well as psychological strategies, physical strategies such as exercise and transcutaneous electrical nerve stimulation (TENS), and surgery. Improvement of function may be a more important treatment goal than relief of pain. PMID- 8469200 TI - Fragile X syndrome. The most common cause of familial intellectual handicap. PMID- 8469202 TI - TENS in refractory angina pectoris. Three case reports. AB - OBJECTIVE: To demonstrate the use of transcutaneous electrical nerve stimulation (TENS) in the treatment of refractory angina pectoris. CLINICAL FEATURES: Three cases are presented. Patient 1 was a 56-year-old man with a 20-year history of angina pectoris. Angiography revealed extensive stenoses of coronary arteries. He was deemed unsuitable for coronary bypass surgery due to significant distal coronary disease. Patient 2 was an 81-year-old woman with angina that responded poorly to increasing drug therapy: she also had extensive stenoses but was judged unsuitable for surgery. Patient 3 was a 69-year-old man who had previously undergone two coronary bypass procedures and presented with unstable rest angina. The patient was deemed unsuitable for a third coronary artery bypass operation due to distal disease and the small calibre of the intermediate artery. INTERVENTION AND OUTCOME: Each patient had TENS added to their treatment regimen (one hour twice a day for Patient 1; one hour three times a day for Patients 2 and 3). Patient 1 experienced a marked reduction in pain which lasted for over a year before symptoms of angina again worsened. Patient 2 has experienced no further pain of angina except on occasions when her TENS unit was not working or she neglected to use it as prescribed. Patient 3 had been free of angina from commencement of TENS therapy on review three months later. CONCLUSION: TENS may be useful in the treatment of angina pectoris which is refractory to medical therapy when the patient is not suitable for revascularisation procedures or revascularisation has failed. The mechanism of action is probably a combination of analgesia per se and inhibition of sympathetic nervous stimulation of the heart. PMID- 8469201 TI - Adult T cell leukaemia lymphoma in a non-aboriginal Australian woman with no apparent risk factors. AB - OBJECTIVE: To present a case of adult T cell leukaemia lymphoma (ATLL) in a non Aboriginal Australian woman with no apparent risk factor. CLINICAL FEATURES: A 43 year-old Australian woman of European descent presented with a febrile illness associated with generalised lymphadenopathy and splenomegaly. INVESTIGATIONS: There was lymphocytosis in the peripheral blood with a T helper cell phenotype. There were also lytic bone lesions with associated hypercalcaemia. HTLV-1 antibody was detected by agglutination assay and confirmed by western blot test. TREATMENT AND OUTCOME: After initial response to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), she relapsed and died with central nervous system involvement eight months after the initial diagnosis. CONCLUSION: To our knowledge this is only the third case of ATLL in a non Aboriginal person in Australia. PMID- 8469203 TI - Planning bedside teaching--4. Teaching around the patient. PMID- 8469204 TI - Magnetic resonance imaging of lesions in the abdomen. PMID- 8469205 TI - First aid treatment of jellyfish stings in Australia. Response to a newly differentiated species. AB - Vinegar has been shown to inhibit neomatocyst discharge in Chironex fleckeri, the deadly north Australian box-jellyfish, and application of vinegar has become accepted first aid, not only for box-jellyfish stings, but also for stings by other Australian jellyfish. However, in a newly differentiated species of Physalia in Australian waters, which causes severe envenomation, vinegar was found to cause discharge in up to 30% of neomatocysts. In treating these stings, the use of vinegar is not recommended as it may increase envenomation. Stings from the single-tentacled Physalia utriculus (the "bluebottle") are not severe, tentacles with unfired nematocysts rarely adhere to the victim's skin and vinegar dousing is not required. Vinegar treatment is therefore an unnecessary step in the first aid management of any Physalia sting but remains an essential first aid treatment for all cubozoan (box) jellyfish tested to date. PMID- 8469206 TI - Chloroquine-resistant Plasmodium vivax: how common? PMID- 8469207 TI - Chloroquine-resistant Plasmodium vivax: how common? PMID- 8469209 TI - Ambient environment may affect saliva ferning fertility test. PMID- 8469208 TI - Development of clinically significant resistance to norfloxacin given for Campylobacter diarrhoea. PMID- 8469210 TI - Donation and retrieval of cadaveric organs in Australia. PMID- 8469211 TI - Are Papanicolaou recalls worthwhile? PMID- 8469212 TI - Children's blood lead levels and environmental lead contamination. PMID- 8469213 TI - Changes in the Australian diet. PMID- 8469214 TI - Reproducibility of coagulation studies in suspected hepatic and pancreatobiliary disease. PMID- 8469215 TI - Bilateral avascular necrosis of the head of the femur. PMID- 8469216 TI - Ethics in aboriginal research. PMID- 8469217 TI - Rare tumors in childhood: pathological aspects. Experience of the Kiel Pediatric Tumor Registry. AB - A wide variety of rare tumors can occur in childhood and adolescence. Tumors can be rare in any age group; common tumors of adults can appear in childhood and adolescence, and many rare tumors and tumor-like lesions show a predilection for younger age groups. Comparatively frequent tumors can present with rare histologic features or can occur in rare atypical locations, and, finally, seemingly common but, in fact, rare tumors have to be distinguished from truly common but rarely recognized tumors. Thus, the spectrum of rare tumors is broad, reflecting the fluent reality of life. PMID- 8469218 TI - Localized dumbbell neuroblastoma: a study of 25 cases treated between 1982 and 1987 using the same protocol. AB - Among the 108 non-metastatic neuroblastomas treated at the Institut Gustave Roussy between 1982 and 1987, 25 dumbbell neuroblastomas were observed. Therapeutics included: 1) an initial laminectomy in forms with neurological deficit; 2) surgical excision of the primary tumor; 3) preoperative chemotherapy in children in which the primary tumor was considered as unresectable at diagnosis and postoperative chemotherapy in cases of incomplete resection; and 4) radiation therapy on macroscopic residual disease. Fifteen out of 25 (60%) presented a neurological deficit. A laminectomy was performed in 14 cases. Neurological recovery was good in 4 cases, partial in 4 cases, and absent in 4 cases. Two patients were worse after the procedure. The event-free survival was 88%. This high survival rate is linked: 1) to the non-metastatic stage; 2) to a high proportion of children under 1 year of age (18/25) (median age = 7 months); and 3) to a high proportion of thoracic location (12/25). The high incidence of macroscopically incomplete excision (13/25) did not jeopardize the prognosis. Out of the 22 survivors, there were 8 cases of major neurological sequellae (36%) and 5 cases of major orthopedic ones (26%). The coexistence of a serious functional prognosis and an excellent vital prognosis for these patients has led us to analyse the therapeutic modalities, to reevaluate the necessity of routine initial neurosurgical removal by laminectomy and to discuss the use of first line chemotherapy. PMID- 8469219 TI - Leukemic blasts with markers of four cell lineages in Down's syndrome ("megakaryoblastic leukemia"). AB - Among 16 patients with Down's syndrome (DS) and acute leukemia admitted to our department during a ten year period, 6 were diagnosed as acute megakaryoblastic leukemia (AMkL). The diagnosis was based on clinical and hematologic criteria, confirmed in three patients with the use of monoclonal antibodies (MoAb) specific for megakaryocytic antigens. In these three, and in a fourth patient, the leukemic blasts were positive for other myeloid, lymphoid and erythroid markers in MoAb testing. We suggest that AMkL in DS is a mixed lineage leukemia with blasts presenting a variety of cell surface antigens, indicating origin from an early progenitor cell with the capability of megakaryocytic differentiation. Of the 6 patients with AMkL, 4 treated with standard AML protocols are in complete continuing remission (CCR) with observation periods from 57+ to 148+ months. PMID- 8469220 TI - Langerhans cell histiocytosis in childhood: results from the Italian Cooperative AIEOP-CNR-H.X '83 study. AB - Ninety patients with biopsy-proven Langerhans cell histiocytosis (LCH) were enrolled from June, 1983, to December, 1988, in the multicenter AIEOP-CNR-H.X. '83 study. They were divided into two groups: poor prognosis (PP), comprising 11 children with organ dysfunction (OD), and good prognosis (GP), made up of 79 patients without OD. Eighty-four patients were evaluable for treatment results. Among GP patients, 16 with a single lesion received only local treatment, while 59 entered a clinical trial of immunotherapy and/or monochemotherapy with vinblastine (VBL). Nonresponders, sequentially received doxorubicin (ADM) and then etoposide (VP16). PP patients were treated with 4 week cycles of vincristine, ADM, cyclophosphamide, and prednisone for nine courses. The overall survival was 92.8% (100% for GP patients and 45.5% for PP patients) at 48 months. The complete response (CR) rates for immunotherapy, VBL, ADM, and VP16 were 10%, 62.9%, 42.8%, and 88.2%, respectively. Two of the 11 PP patients had a CR (18.2%), while six died and three are still alive with recurrent disease. The overall incidence of disease-related disabilities was 47.7%, while that of diabetes insipidus was 20%. Monochemotherapy is probably adequate in GP patients, while more effective treatments are needed for PP patients. PMID- 8469221 TI - Cytosine-arabinoside, vincristine, and prednisolone in the treatment of children with disseminated Langerhans cell histiocytosis with organ dysfunction: experience at a single institution. AB - Fifty-two pediatric patients with Langerhans cell histiocytosis (LCH) were diagnosed at the Emma Kinderziekenhuis (EKZ) in Amsterdam over a 20-year period. Eight patients with multiorgan involvement with organ dysfunction and ten patients with multi-organ involvement without organ dysfunction received chemotherapy containing cytosine-arabinoside, vincristine, and prednisolone as part of their treatment. Five of the 8 patients (63%) with organ dysfunction and eight of the 10 (80%) without the organ dysfunction who needed chemotherapy because of the deteriorating of symptoms despite conventional therapy are presently in complete clinical remission. Two of those with organ dysfunction have died. Four of the total 18 patients developed diabetes insipidus either as an initial symptom or during the course of the disease. These results in both groups compare satisfactorily with other chemotherapeutic regimens, and since this combination is only mildly toxic, it has been well tolerated. Therefore we would recommend wider experience using this regimen in patients with widespread LCH with organ dysfunction as well as in patients with disseminated LCH in which chemotherapy proved to be necessary. PMID- 8469222 TI - Langerhans cell histiocytosis and acute leukemia: unusual association in two cases. AB - Langerhans cell histiocytosis (LCH) is a non-malignant disorder, whether localized or disseminated, and usually has a favourable prognosis. A possible relationship between LCH and neoplastic diseases has not been assessed up to now even if a few cases have been recorded. We report two new cases of acute leukemia in children with LCH. The first child had acute lymphoblastic leukemia after untreated LCH; the second developed acute promyelocytic leukemia after LCH treated with vinblastine and etoposide. To our knowledge, this is the first case of secondary leukemia after exposure to an epipodophyllotoxin derivative in a child with benign disease. Cooperative studies of large numbers of LCH patients are needed to evaluate a possible association between LCH and acute leukemia, and to identify common risk factors or predisposing agents if such be present. PMID- 8469223 TI - The treatment of malignant scala posterior tumors in children: II. Preliminary result of the pre- and postoperative adjuvant chemotherapy of scala posterior tumors. AB - Ten children with posterior scala tumor infiltrating the surrounding brain substance and/or the brain stem entered in the present study with preoperative chemotherapy. In 8 of the 10 cases regression and necrosis of the tumor were seen by CT examination after the preoperative therapy. The diameter of the tumor decreased on the average by 35.6% (14.0-74.3%). The main side effect was granulocytopenia. According to our observation, the preoperative therapy enables a more radical surgery in some cases of medulloblastoma and ependymoma. Further observations are necessary to confirm these preliminary results. PMID- 8469225 TI - Focal nodular hyperplasia of the liver in childhood. PMID- 8469224 TI - Phase I trial of trimetrexate in pediatric solid tumors: a Pediatric Oncology Group study. AB - Trimetrexate (TMTX), a lipophilic antifol, was evaluated in a Pediatric Oncology Group (POG) Phase I trial in children with refractory solid tumors. TMTX was administered intravenously daily x 5 every three weeks. Starting dose was 6.4 mg/m2/day. Dose was escalated by 20% until the maximal tolerated dose was reached. A total of 75 courses were administered to 26 children. The major toxicity was myelosuppression, of which neutropenia and thrombocytopenia were most prominent. Rash, mucositis, and transient liver enzyme elevations were infrequently seen. Responses were observed in children with brainstem glioma, neuroblastoma, and renal cell carcinoma. The recommended Phase II dose using this schedule is 9.2-11 mg/m2/day depending on how heavily the patient has been treated prior to initiating this therapy. PMID- 8469226 TI - Cytogenetic abnormalities in a disseminated medulloblastoma. AB - A 3-year-old girl developed central nervous system, bone and bone marrow metastases, and hypercalcaemia shortly after presentation with medulloblastoma. Cytogenetic studies of the involved bone marrow showed multiple abnormalities including iso(17q). This chromosome rearrangement has been reported in other cases of recurrent or disseminated medulloblastoma. More studies are required relating the karyotypes of medulloblastomas to long-term outcome to determine if the presence of iso(17q) is a prognostic factor in this malignancy. PMID- 8469227 TI - Comparison of serial PET and MRI scans in a pediatric patient with a brainstem glioma. AB - Profound clinical deficits may be associated with insults to the brainstem, making management of patients with brainstem gliomas very complex. Small changes in the radiographic appearance of a brainstem tumor may be associated with significant clinical deterioration. Furthermore, both magnetic resonance imaging and computed tomography are frequently unable to differentiate between therapy related tissue reactions and progressive tumor. Two clinical scenarios particularly difficult to resolve include: (1) transient radiographic and clinical deterioration following hyperfractionated radiotherapy, and (2) clinical deterioration in a patient who has failed initial therapy, but has stable radiographic findings following a second therapy. We report a child with a pontine glioma whose tumor progression was demonstrated more convincingly with a 18F-deoxyglucose positron emission scan than with magnetic resonance imaging. PET scans may be helpful in confirming that tumor progression is responsible for clinical deterioration in a patient whose MRI scans remain stable. PMID- 8469228 TI - Cerebral non-Hodgkin's lymphoma discovered when treating Hodgkin's disease. AB - Case report of the appearance of a highly malignant cerebral non-Hodgkin's lymphoma of a diffuse large cell type, type B, occurring at the immediate onset of chemotherapy for a stage IV (mediastino-pulmonary) Hodgkin's disease (nodular sclerosis) diagnosed in a 16-year-old boy. The treatment of this cerebral lymphoma associated primary chemotherapy with high dose methotrexate, high dose aracytine, etoposide, and ifosfamide. The chemotherapy proved to be highly efficient, producing complete remission. Thoracic and abdominal irradiation for Hodgkin's disease was performed concomitantly with chemotherapy for the non Hodgkin's lymphoma. This treatment was followed by 36 Gy of cerebral irradiation. Thirty-six months after the discovery of the cerebral non-Hodgkin's lymphoma the patient was still disease-free and doing well. PMID- 8469229 TI - Immunizations pay off, Hib meningitis cases 'thud'. PMID- 8469230 TI - 100 years of caring for health: MNA and public health nursing. PMID- 8469231 TI - Transcripts originating in intron 1 of the HSD11 (11 beta-hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive. AB - There is evidence for the presence in the kidney of more than one isoform of 11 beta-hydroxysteroid dehydrogenase (11HSD), an enzyme that interconverts cortisol and cortisone (in rodents, corticosterone and 11-dehydrocorticosterone). A specific isoform might arise from transcripts in the kidney that are known to originate in intron 1; translation from these transcripts is predicted to initiate at the codon that in the full-length rat enzyme encodes Met27. Alignment of the full-length rat and human 11HSD sequences with other members of the short chain dehydrogenase family suggests that initiation of translation at Met27 might yield a functional enzyme, since the amino-termini of most of these enzymes occur at equivalent positions. We confirmed that short transcripts are found in the kidney and are detectable at lower levels in the liver and lung. In vitro transcription and translation of short cDNA demonstrated that the AUG encoding Met27 is indeed a functional initiation codon. However, Chinese hamster ovary cells transfected with short cDNA in the pCMV4 vector expressed apparently low levels of the corresponding truncated polypeptide and had no 11HSD activity. Thus, the functional significance of transcripts originating in intron 1 is unclear. PMID- 8469232 TI - Trophoblast-specific transcription from the mouse placental lactogen-I gene promoter. AB - We have isolated the gene encoding mouse placental lactogen-I and characterized the promoter region of this gene by transient and stable transfection. Promoter sequences extending 274 basepairs (bp) up-stream from the start site of transcription contain all of the elements necessary for maximal expression upon transient transfection into the rat choriocarcinoma Rcho-1 cell line; these Rcho 1 cultures contain both proliferative trophoblast stem cells and terminally differentiated trophoblast giant cells. In stably transfected cell lines, expression from this promoter increases as the percentage of differentiated cells in the culture increases. In contrast to these results in trophoblast cells, the 274-bp promoter as well as a promoter region extending 2700 bp up-stream of the transcriptional start site are unable to drive transcription in a variety of other cell types. Mutational and protein binding analyses indicate that two AP-1 sites are required for maximal expression in Rcho-1 cells, and that the composition of the AP-1 transcription factor may vary as differentiation in the cell culture increases. In addition to these two AP-1 sites, at least one other element appears to be critical for promoter activity in trophoblast cells. PMID- 8469233 TI - The gene encoding the human corticostatin HP-4 precursor contains a recent 86 base duplication and is located on chromosome 8. AB - The human neutrophil-derived cationic peptide HP-4 exhibits corticostatic activity on adrenal cells and is an L-type calcium channel agonist at nanomolar concentrations. Complementary DNA clones encoding the HP-4 precursor have been isolated from a human bone marrow cDNA library by screening with oligonucleotide probes. The nucleotide sequence shares about 72% identity with the cDNA encoding defensin HP-1, but differs from it, and from other genes of this family characterized to date, by an extra 83-base segment. This extra segment is not adjacent to an intron and is apparently the result of a recent duplication within the coding region corresponding to most of the mature HP-4 peptide. The predicted amino acid sequence shows the HP-4 precursor structure to be typical of this family of molecules. By analysis of DNA from a pannel of hamster/human hybrid cell lines, the HP-4 gene was found to be on chromosome 8, as is the gene for human peptide HP-1. Comparison with the few sequences of other corticostatin/defensin genes available does not indicate distinct lineages of corticostatic and noncorticostatic peptides, since HP-1 and HP-4 cDNA sequences share more identity with each other than either shares with cDNAs encoding rabbit MCP-1 or MCP-2, or guinea pig GNCP-1. PMID- 8469234 TI - Prolactin augments progesterone-dependent uteroglobin gene expression by modulating promoter-binding proteins. AB - The sequence-specific binding of endometrial nuclear proteins to uteroglobin 200 (UG200) (-194/+9), the 203-base pair 5'-flanking region of the rabbit uteroglobin gene, and UG99 (-170/-85), a subfragment of UG200, was compared with gel shift assays. PRL + progesterone treatment of estrous rabbits produced a 6- to 7-fold increase in the primary shift compared to progesterone alone. PRL + progesterone treatment of long-term ovariectomized rabbits increased the primary shift 60% over progesterone alone, which increased the primary shift 30-fold over similarly treated estrous rabbits. The primary shift was eliminated when rabbits were treated with progesterone + estradiol benzoate (E2Bz). Changes in the steady state levels of UG mRNA paralleled changes in the intensity of the primary gel shift. Southwestern blotting revealed four proteins from progesterone-dominated endometrial nuclei that bind UG200. PRL pretreatment produced a 3- to 12-fold increase in each of the proteins. Protein binding was eliminated by E2Bz. A 100 kilodalton (kDa) protein from progesterone-dominated endometrial nuclei was UV cross-linked to UG200 and UG99. An additional protein was detected by each probe with long autoradiographic exposure. PRL pretreatment increased the 100-kDa protein, whereas covalent attachment of the 100-kDa protein to UG promoter DNA was eliminated by E2Bz. UV cross-linking in situ was used to identify the 100-kDa protein as responsible for the primary shift. Collectively, these experiments provide compelling evidence that PRL augments the progesterone-dependent transcription of the UG gene in the uterus by regulating at least one and as many as four proteins that bind to the UG promoter. PMID- 8469235 TI - High affinity and specificity of dimeric binding of thyroid hormone receptors to DNA and their ligand-dependent dissociation. AB - The thyroid hormone receptors are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related steroid/thyroid hormone receptor superfamily. We report here the high affinity and specificity of dimeric DNA binding of human thyroid hormone receptor-alpha 1 (hTR alpha 1) and hTR beta 1 and the effect of T3 on its DNA binding. Gel mobility shift assay showed that hTR alpha 1 and -beta 1 bind to the rat GH-thyroid hormone response element (TRE) and rat malic enzyme (rME)-TRE as a monomer, dimer, and oligomer in the absence of T3 and bind to an irrelevant DNA sequence from the adenovirus 5 promoter only as a monomer. In competition studies using unlabeled TRE, dimer binding was displaced by lower concentrations of TRE than was the monomer, indicating that the dimeric binding has higher affinity than the monomer binding. These results suggest that the formation of dimers of TR increases the specificity and affinity for the response element. Surprisingly, T3 disrupted dimer binding and increased the intensity of monomer binding to rME-TRE in a dose-dependent manner. This does not occur with the rat GH-TRE. We also demonstrate that this disruption of dimeric binding by T3 occurred on a TRE formed by a direct repeat and not on a palindromic TRE. Furthermore, a mutant hTR beta (Mf), which has no detectable ligand-binding activity because of a glycine to arginine substitution at amino acid 340 in the hormone-binding domain, does not show dissociation from rME-TRE after the addition of T3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469236 TI - Identification of residues in the estrogen receptor that confer differential sensitivity to estrogen and hydroxytamoxifen. AB - We have generated mutant mouse estrogen receptors which differ in their sensitivity to estrogen and the antiestrogen 4-hydroxytamoxifen. Mutation of the glycine at position 525 and the methionine and/or serine at positions 521/522 virtually abolishes the ability of the receptor to bind estradiol and stimulate transcription. In contrast, the mutant receptors retain the partial agonist activity exhibited by the wild-type receptor in the presence of 4 hydroxytamoxifen. The mutations do not affect the expression and DNA-binding activity of the receptor, but do abolish the estrogen-induced increase in the mobility of the receptor-DNA complex observed with the wild-type receptor. Other mutant receptors that were able to bind and stimulate transcription in the presence of estradiol also failed to show the agonist-induced increase in the mobility of the receptor-DNA complex, suggesting that it is unlikely to reflect the formation of a hormone-dependent transcriptional activation function. PMID- 8469237 TI - Identification of a hormone-dependent phosphorylation site adjacent to the DNA binding domain of the chicken progesterone receptor. AB - We have previously identified three phosphorylation sites in chicken progesterone receptor (PR) isolated from the cytosol of chicken oviducts. Several lines of evidence suggested that there might be additional phosphorylations that occur only in the nuclear compartment. We have reexamined the phosphorylation of the PR using whole cell extracts and have identified a second hormone-dependent phosphorylation site (Ser367) which is located on the amino-terminal side of the DNA-binding domain. This site also contains a Ser-Pro consensus sequence, as do the three previously reported sites. There are four Ser-Pro sequences in chicken PR, and all four are phosphorylated. Two of the sites showed substantial phosphorylation in the absence of hormone, with some enhancement in response to hormone, whereas two of the sites showed very little phosphorylation in the absence of hormone. This suggests either that despite the Ser-Pro consensus sequences, the sites are phosphorylated by different enzymes, or that binding hormone changes the conformation of the protein sufficiently to expose the two hormone-dependent phosphorylation sites. PMID- 8469238 TI - Mullerian inhibiting substance requires its N-terminal domain for maintenance of biological activity, a novel finding within the transforming growth factor-beta superfamily. AB - Mullerian inhibiting substance (MIS)/anti-Mullerian hormone is a differentiation factor that causes regression of the Mullerian duct in the developing male fetus and an apparent sex reversal of the fetal ovary when inappropriately exposed to it. The purified product is a 140-kilodalton glycoprotein composed of two identical subunits. We show that a C-terminal fragment of MIS, which shares homology with transforming growth factor-beta, causes regression of the Mullerian duct and inhibits the biosynthesis of aromatase in the fetal ovary. However, both activities are enhanced dramatically by addition of the N-terminal portion of MIS. Under conditions where potentiation occurs, the N- and C-terminal domains of MIS reassociate. These results indicate that the N-terminus of MIS, unlike that of the other members of the transforming growth factor-beta family, plays a role in maintaining the biological activity of the C-terminus. PMID- 8469239 TI - Structural organization and regulation of the gene for the androgen-dependent glutathione peroxidase-like protein specific to the mouse epididymis. AB - Genomic clones containing the gene for the glutathione peroxidase-like androgen regulated murine epididymal protein of 24 kilodaltons (arMEP24) were isolated. A 9-kilobase DNA fragment was sequenced and found to contain the entire coding region of the gene, which is divided into five exons. The exact sizes and boundaries of the exon blocks were deduced by comparison with the cDNA sequence. One major and four weak transcription initiation sites in the epididymis were localized by primer extension. The promoter of the gene does not contain a conventional TATA box immediately up-stream of the start site; rather, the sequence TATCA occurs at residue -35. Two CAAT boxes in opposite orientation and two putative binding sites for the transcription factor Sp1 were identified up stream of the TATA-like box. To localize the cis-acting sequences responsible for androgen regulation of expression, fragments of the arMEP24 gene promoter region were cloned in front of the luciferase (LUC) reporter gene and cotransfected with an androgen receptor expression vector into CV-1 cells in a transient assay. LUC activities of CV-1 cells grown in the presence of various concentrations of 5 alpha-dihydrotestosterone were compared to LUC activities of untreated controls. The DNA fragment containing up to 200 nucleotides up-stream from the major transcription start site was sufficient for the full promoter activity, but not for the responsiveness to androgen induction. Depending on the 5 alpha dihydrotestosterone concentration, a 2- to 4-fold induction of LUC activity was found if a -1797 to -167 arMEP24 gene fragment was used linked to the reporter gene driven by either the homologous promoter or the heterologous thymidine kinase promoter. Two or three copies of the imperfect palindromic sequence TGTTGAgagAGAACA, found at position -896 to -882 in the gene and resembling the consensus steroid hormone-responsive element, are able to confer androgen regulation to the thymidine kinase promoter independently of their orientation. These findings support evidence that transcriptional regulation of the arMEP24 gene occurs via the sequence TGTTGAgagAGAACA. Homologies found in the sequence up stream of the promoter with several putative binding sites for erythroid-specific trans-acting regulatory proteins are discussed. Finally, the arMEP24 gene is located by in situ hybridization in the [A2-A4] region of mouse chromosome 13. PMID- 8469240 TI - Identification and characterization of a GC-rich promoter of the human parathyroid hormone-related peptide gene. AB - The human PTH-related peptide (PTHrP) gene comprises eight exons spanning more than 15 kilobases of genomic DNA. The gene has a highly complex controlling region, which contains four alternatively spliced, noncoding exons and at least two putative promoters, one 5' of exon 1A (up-stream TATA element) and the other 5' of exon 2 (down-stream TATA element). To define important cis regulatory sequences of this gene, a functional dissection of PTHrP 5'-flanking DNA was initiated, using chimeric PTHrP-chloramphenicol acetyltransferase (CAT) constructs. This analysis was carried out in PTHrP-negative human renal carcinoma cells, so that RNA derived from transfected DNA could be studied without interference from endogenous PTHrP sequences. Of the initial series of constructs prepared, the most active was a 1.1-kilobase BamHI-HindIII PTHrP-CAT plasmid containing 350 basepairs of DNA 5' of exon 1C and extending into exon 3. Analysis of transfection products by RNase protection and primer extension revealed that this region contains a previously unrecognized promoter of the gene. This element is located immediately 5' of exon 1C, is active in transfected cells when cloned in isolation up-stream of the CAT gene, and appears to be functional in a number of cell lines and tissues on the basis of primer extension analysis. Unlike the other two PTHrP gene promoters, this element is GC rich and does not possess canonical TATA or CAAT sequences. The human PTHrP gene is one of a handful of genes that appear to use both TATA and GC-rich promoter elements. PMID- 8469241 TI - Transcriptional activation of the insulin-like growth factor-II gene during myoblast differentiation. AB - Insulin-like growth factor-II (IGF-II) is a secreted 67-amino acid peptide that functions principally as a prenatal growth regulator in mammals. To date, the mechanisms involved in the stimulation of IGF-II expression in the embryo and its attenuation after birth are unknown. Recent studies have shown that IGF-II mRNA and protein are induced during the terminal stages of muscle development in vitro, and that IGF-II may act as an autocrine differentiation agent for skeletal myoblasts. We now have investigated the regulation of IGF-II gene expression in muscle cells. Steady state levels of IGF-II mRNA increased by more than 30-fold during terminal differentiation of the C2 mouse myoblast cell line. Transcription run-on experiments using isolated muscle cell nuclei and direct analysis of nuclear RNA each demonstrated a greater than 10-fold rise in nascent IGF-II mRNA during cellular differentiation, and ribonuclease protection experiments showed that more than 95% of IGF-II mRNAs initiated in noncoding exon 3, implying that transcriptional activation occurs principally through promoter 3, the most 3' of the three mouse IGF-II gene promoters. Analysis of chromatin structure around the IGF-II gene in C2 cells revealed four major and four minor DNase-I-hypersensitive sites, but did not provide insight into the mechanisms of gene activation, since all sites were present in proliferating and differentiating cells. Gene transfer experiments showed that promoter 3 was at least 50-fold more active than promoter 1 or 2 in C2 cells, but the functional assessment of nearly 26 kilobases of additional DNA within the IGF-II locus by an "enhancer trap" approach did not delineate any chromosomal regions capable of mediating differentiation-specific gene activation. Our results demonstrate that muscle cells encode mechanisms for activating IGF-II gene transcription and suggest that these cells may be excellent models for identifying the developmentally regulated factors that control IGF-II gene expression. PMID- 8469242 TI - The global impact of penicillin: then and now. PMID- 8469243 TI - Clinical correlates of pathologic findings: case 1. PMID- 8469244 TI - Narrative and medicine. PMID- 8469245 TI - Physicians practicing other occupations, especially literature. AB - Literature has been the favored nonmedical pursuit of physicians probably because the practice of medicine is suffused with narratives, the patient's history being one. Arthur Conan Doyle regarded medicine as a "grim romance," Somerset Maugham as an opportunity to see "life in the raw," and William Carlos Williams treated "the patient as a work of art." These sentiments may be linked to humanistic medicine. At some medical schools, literature is taught in the context of and integrated with medicine in an attempt to enhance ethics and empathy which were explicitly expressed by some physician-writers. PMID- 8469246 TI - Prevalence of thyroid autoantibodies in ambulatory elderly women. AB - Major improvements in thyroid autoantibody testing have now become widely available. Seventy-five elderly ambulatory women from a senior citizens' center (mean age 74.5 yrs) were studied to reassess the prevalence of thyroid autoantibodies and to demonstrate how such tests related to clinical signs and symptoms of thyroid disease. We used the enzyme-linked immunoassay (ELISA) technique for the measurement of autoantibodies to thyroglobulin (hTg) and thyroid peroxidase (hTPO) (as microsomal antigen), since ELISA systems are economical, highly sensitive and specific for population screening. Autoantibodies to hTPO (hTPO-Ab) were present in 44% and hTg autoantibodies (hTg Ab) in 32% of the study group. Ten women (13.3%) had elevated thyrotropin (TSH) levels. An elevated serum TSH was associated with the presence of hTPO-Ab in varying concentrations. The mean TSH value of 7.2 microIU/mL in those women with hTPO-Ab was significantly higher than the mean of 4.7 microIU/mL found in those women without thyroid autoantibodies (p < 0.01). However, additional testing for hTg-Ab was of little clinical value. These data indicate the high prevalence of thyroid autoimmune disease in the elderly female population. We conclude that screening for thyroid dysfunction is best achieved by the measurement of serum TSH in all women over the age of 60 years. The measurement of hTPO-Ab, but not hTg-Ab, was helpful in confirming the cause of thyroid failure in the elderly female population. PMID- 8469247 TI - MRI documentation of hemorrhage into post-traumatic subdural hygroma. AB - Rapid enlargement of a post-traumatic hygroma was demonstrated by MRI in a patient who had sequential studies performed after head injury. The enlargement was shown to be due to hemorrhage into the hygroma. PMID- 8469248 TI - A case report of neurologic improvement following treatment of paraneoplastic cerebellar degeneration. PMID- 8469249 TI - Osteoporosis: on the verge of rational effective therapy? PMID- 8469250 TI - The pathophysiology and molecular genetics of beta thalassemia. AB - Review of the pathophysiology and molecular basis of beta thalassemia reveals that an extremely heterogeneous group of molecular defects can give rise to a relatively uniform clinical and hematological phenotype that is primarily the result of the excess of free alpha-globin chains that accumulate in the face of absent or markedly reduced beta-globin chain synthesis. Despite the molecular heterogeneity, it has been possible to establish highly accurate and efficient DNA-based prenatal diagnosis for beta thalassemia. Important progress is also being made in the area of gene therapy for beta thalassemia. PMID- 8469251 TI - A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans Affairs Cooperative Study on Valvular Heart Disease. AB - BACKGROUND: Mechanical heart valves are durable but thrombogenic, and their use requires that the patient receive anticoagulants. In contrast, bioprosthetic valves are less thrombogenic, but they have limited durability because of tissue deterioration. METHODS: To compare the outcomes of patients who receive these two types of valves, we randomly assigned 575 men scheduled to undergo aortic-valve or mitral-valve replacement to receive either a mechanical or a bioprosthetic valve. The primary end points were death from any cause and any valve-related complication. RESULTS: During an average follow-up of 11 years, there was no difference between the two groups in the probability of death from any cause (11 year probability for mechanical valves, 0.57; for bioprostheses, 0.62; P = 0.57) or in the probability of any valve-related complication (0.65 and 0.69, respectively; P = 0.39). There was a much higher rate of structural valve failure among patients who received bioprosthetic valves (11-year probability, 0.15 for the aortic valves and 0.36 for the mitral valves) than among those who received mechanical valves (no valve failures; P < 0.001). However, this difference was offset by a higher rate of bleeding complications among patients with mechanical valves than among those with bioprosthetic valves (11-year probability, 0.42 and 0.26, respectively; P < 0.001) and by a greater frequency of peri-prosthetic valvular regurgitation among patients with mechanical mitral valves than among those with mitral bioprostheses (11-year probability, 0.17 and 0.09, respectively; P = 0.05). CONCLUSIONS: After 11 years, the rates of survival and freedom from all valve-related complications were similar for patients who received mechanical heart valves and those who received bioprosthetic heart valves. However, structural failure was observed only with the bioprosthetic valves, whereas bleeding complications were more frequent among patients who received mechanical valves. PMID- 8469252 TI - Male hypogonadism with gynecomastia caused by late-onset deficiency of testicular 17-ketosteroid reductase. AB - BACKGROUND: 17-Ketosteroid reductase deficiency results in male pseudohermaphroditism because conversion of the weak androgen androstenedione to the more potent androgen testosterone is impaired. If a late-onset form exists, hypogonadism and gynecomastia caused by decreased testosterone production and increased estrogen production, respectively, would be expected as the major clinical manifestations in men. METHODS: We studied 48 male subjects, ranging from 14 to 26 years of age, who had idiopathic pubertal gynecomastia. Serum concentrations of gonadal and adrenal steroid hormones were measured before and after the administration of corticotropin and after the combined administration of chorionic gonadotropin and dexamethasone for three days. RESULTS: We identified three unrelated subjects (ages, 16, 17, and 26 years) with results indicative of a partial deficiency of testicular 17-ketosteroid reductase. The three subjects had gynecomastia as well as decreased libido and impotence. Their mean (+/- SD) base-line serum androstenedione and estrone concentrations were elevated as compared with the levels in the 45 subjects without this enzyme deficiency (androstenedione, 380 +/- 70 vs. 110 +/- 70 ng per deciliter [13 +/- 2 vs. 4 +/- 2 nmol per liter]; estrone, 138 +/- 12 vs. 46 +/- 9 pg per milliliter [511 +/- 44 vs. 170 +/- 33 pmol per liter]). After the administration of chorionic gonadotropin, the mean serum androstenedione concentration in these three subjects was 910 +/- 48 ng per deciliter (32 +/- 2 nmol per liter) and the mean serum estrone concentration was 260 +/- 16 pg per milliliter (962 +/- 59 pmol per liter). The mean serum testosterone concentration at base line was 210 +/- 80 ng per deciliter (7.4 +/- 2.8 nmol per liter) in the 3 subjects, as compared with a value of 410 +/- 12 ng per deciliter (14.4 +/- 0.42 nmol per liter) in the 45 other subjects, and it did not increase in response to the administration of chorionic gonadotropin. The concentrations of androstenedione and estrone in spermatic venous serum were 19 times higher and 73 times higher, respectively, than in normal men. The serum concentrations of follicle stimulating hormone and luteinizing hormone in these three subjects were inappropriately low, suggesting the presence of hypogonadotropic hypogonadism. CONCLUSIONS: A late-onset form of testicular 17-ketosteroid reductase deficiency can cause gynecomastia and hypogonadism in men. PMID- 8469253 TI - Cyclospora species--a new protozoan pathogen of humans. AB - BACKGROUND: Organisms referred to as "cyanobacterium-like bodies" have now been identified worldwide in the feces of both immunocompetent and immunocompromised patients with diarrhea. Organisms with a similar appearance have been isolated from Peruvian patients since 1985. From 1988 to 1991 we studied prospectively two cohorts of infants and young children infected with this organism. We now attempt to identify it. METHODS: Fecal samples were collected weekly from the children and examined with the use of acid-fast staining and staining with a monoclonal antibody specific for cryptosporidium. Stools positive for cyanobacterium-like bodies were preserved in potassium dichromate and exposed to conditions allowing coccidian sporulation and excystation. Both unsporulated and sporulated oocysts were fixed by freeze-substitution techniques and then examined by electron microscopy. RESULTS: Organisms isolated from the feces of Peruvian patients and two patients from the United States were identified as belonging to the coccidian genus cyclospora, after sporulation and excystation of the oocysts according to standard techniques. Complete sporulation occurred within 5 to 13 days in oocysts maintained in potassium dichromate at 25 or 32 degrees C. Complete excystation resulted in the liberation of two sporozoites from the two sporocysts within each oocyst (cryptosporidia have four naked sporozoites within each oocyst). The presence of organelles characteristic of coccidian organisms was confirmed by electron microscopy. CONCLUSIONS: We have identified organisms of the genus cyclospora that are remarkably similar to cryptosporidia in their morphologic features and the diarrheal disease that they produce in humans. The complete life cycle and epidemiology of this new protozoan parasite remain to be described. PMID- 8469254 TI - Management of fever in patients with cancer and treatment-induced neutropenia. PMID- 8469255 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-1993. A 57-year-old man with chronic lymphedema and enlarging purple cutaneous nodules of the leg. PMID- 8469256 TI - My three valves. PMID- 8469257 TI - Physicians' autonomy--the relation between public and professional expectations. PMID- 8469258 TI - HIV infection in rural Florida. PMID- 8469259 TI - HIV infection in rural Florida. PMID- 8469260 TI - HIV infection in rural Florida. PMID- 8469261 TI - Central nervous system toxoplasmosis in AIDS. PMID- 8469262 TI - Central nervous system toxoplasmosis in AIDS. PMID- 8469264 TI - Cryptococcal meningitis after unusual exposures to birds. PMID- 8469263 TI - Central nervous system toxoplasmosis in AIDS. PMID- 8469265 TI - Complications of gynecologic laparoscopic surgery--a French multicenter collaborative study. PMID- 8469266 TI - CPAP cyst. PMID- 8469267 TI - The Gulf War and infant and child mortality in Iraq. PMID- 8469269 TI - Sequential pathological studies in goats infected intratracheally with Aspergillus fumigatus. AB - Intratracheal inoculation of goats with Aspergillus fumigatus spores resulted in the development of characteristic gross and microscopic lesions. The lesions were restricted to lungs and there was no dissemination of infection to other tissues of the body except liver in one goat 16 days after infection. The experiment was continued for 37 days. Gross changes in lungs were observed up to the 24th day post-infection. The lesions, in general, included congestion and oedema in the first 6 days followed by the development of varying greyish-white nodules in the lungs. Microscopic changes consisted of granulomatous reaction with well developed granulomas in lungs. Hyphae and conidiophores with fruiting bodies of Aspergillus fumigatus could be demonstrated in sections up to 24 days of infection. Reisolation of the fungus consistently was achieved up to 24 days. It is concluded that intratracheal inoculation of Aspergillus fumigatus spores in goats leads to pulmonary aspergillosis up to 24 days. PMID- 8469268 TI - Radiographic features of experimental Candida arthritis in rats. AB - Sprague-Dawley rats were inoculated intravenously (i.v.) with Candida albicans, and limb joints showing signs of Candida-induced arthritis were subjected to radiographic and histologic examination. New bone formation and bone resorption were morbidly enhanced in bones sampled from the arthritic joints. Sparsely distributed needle-shaped calcified deposits began to be formed on bony surfaces in parallel with the onset of joint swelling. The calcified deposits gradually became denser and then covered the bony surfaces almost entirely, giving rise to an exostosis-like profile. In addition to the new bone formation, bone resorption was also observed in regions adjacent to the sites of new bone formation, and punched-out bone lesions were produced. Eventually, severe deformation of joint bones due to new bone formation and bone resorption was evident. Reflecting these unusual radiographic changes, abundant osteoblasts and osteoclasts were demonstrated histologically in the bones. On the basis of these results, possible mechanisms for the induction of arthritis by Candida infection are discussed. PMID- 8469270 TI - Experimental candidiasis in Japanese quail: pathological changes. AB - Candidiasis was experimentally produced in young Japanese quail by oral administration of Candida albicans cells. Lesions were confined to upper digestive tract with most characteristic changes occurring on the mucosa of crop. No lesions were observed in other tissues of the body. The initial changes in the crop were characterized by thickening and yellowish-white necrotic plaques on the mucosa. From 10th day onwards, there was marked thickening and corrugations of the crop mucosa giving it a typical 'turkish towel' appearance. Varying degree of mucosal swelling was also observed in the oesophagus and proventriculus. Two of the infected birds also revealed yellowish-white necrotic plaques on the tongue at 7th and 10th day post-infection. The prominent microscopic lesions in the crop and tongue consisted of hyperkeratosis and parakeratosis with congestion of the subepithelial tissues. Varying degree of parakeratosis and epithelial hyperplasia coupled with subepithelial oedema and hypertrophy of glands was observed in the oesophagus. The proventriculus and small intestine revealed congestion, oedema, mild to marked goblet cell hyperplasia and focal epithelial sloughing. Fungal elements could be demonstrated in the sections of tongue up to 10 days while in crop up to 14 days post-infection. Reisolation of the fungus was consistently achieved from the crop of infected birds throughout the duration of the experiment. PMID- 8469271 TI - AIDS patients are first in line. PMID- 8469272 TI - Japan reviews first guidelines for gene therapy trials. PMID- 8469273 TI - NIH to support embryo bank for mice and rabbits. PMID- 8469274 TI - NIH takes Stewart and Feder off the misconduct beat. PMID- 8469275 TI - Promega extends fight with Roche over Taq enzyme. PMID- 8469276 TI - DNA testing helps British bring better pig to market. PMID- 8469277 TI - Two-way adaptors. PMID- 8469278 TI - Cancer. Fusion potential for vaccines. PMID- 8469279 TI - Immunology. Tolerance by exhaustion. PMID- 8469280 TI - Retroviruses. One and one make four. PMID- 8469281 TI - Magnetic compass orientation. PMID- 8469282 TI - Instability and decay of the primary structure of DNA. AB - Although DNA is the carrier of genetic information, it has limited chemical stability. Hydrolysis, oxidation and nonenzymatic methylation of DNA occur at significant rates in vivo, and are counteracted by specific DNA repair processes. The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils. PMID- 8469283 TI - Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. AB - Expression of globin genes in developing erythroid cells is controlled by upstream locus control regions. Activity of these regions in vivo requires an erythroid-specific nuclear factor (NF-E2) that binds AP-1-like recognition sites. Its tissue-specific component (p45 NF-E2) has been characterized by complementary DNA cloning as a new basic region-leucine zipper protein which dimerizes with a ubiquitous partner to form native NF-E2. PMID- 8469284 TI - Male-driven evolution of DNA sequences. AB - It is commonly believed that the mutation rate is much higher in the human male germ line than in the female germ line because the number of germ-cell divisions per generation is much larger in males than in females. But direct estimation of mutation rates is difficult, relying mainly on sex-linked genetic diseases, so the ratio (alpha m) of male to female mutation rates is not clear. It has been noted that if alpha m is very large, then the rate of synonymous substitution in X-linked genes should be only 2/3 of that in autosomal genes, and comparison of human and rodent genes supported this prediction. As the number of X-linked genes used in the study was small and the X-linked and autosomal sequences were non homologous, and given that the synonymous rate varies among genes, we sequenced the last intron (approximately 1 kb) of the Y-linked and X-linked zinc-finger protein genes (ZFY and ZFX) in humans, orang-utans, baboons and squirrel monkeys. The ratio Y/X of the substitution rate in the Y-linked intron to that in the X linked intron is approximately 2.3, which is close to that estimated from synonymous rates in the ZFY and ZFX genes and implies alpha m approximately 6. This estimate of alpha m supports the view that the evolution of DNA sequences in higher primates is male-driven. It is, however, much lower than the previous estimate and therefore raises a number of issues. PMID- 8469285 TI - Parental-origin-specific epigenetic modification of the mouse H19 gene. AB - The H19 gene produces an abundant developmentally regulated transcript of unknown function in normal embryos. In the mouse it lies on chromosome 7 and is subject to transcriptional regulation by parental imprinting, which results in the maternally inherited gene being expressed and the paternally inherited gene being repressed. Embryos carrying maternal duplication/paternal deficiency for distal chromosome 7 (MatDi7) therefore express a double dose of H19. Here we examine the parental-origin-specific epigenetic modifications that may be involved in this regulation by comparing CpG methylation and nuclease sensitivity of chromatin in MatDi7 embryos with normal littermates. We show that specific sites in the CpG island promoter and 5' portion of the gene are methylated only on the paternal allele. Furthermore, active maternal alleles in chromatin of MatDi7 embryos are more sensitive and accessible to nucleases. Therefore hypermethylation and chromatin compaction in the region of the H19 promoter is associated with repression of the paternally inherited copy of the gene. Most, but not all, of these sites are unmethylated in sperm, with methylation of the paternal promoter occurring after fertilization. These results contrast with our findings for the closely linked and reciprocally imprinted gene encoding insulin-like growth factor II (ref. 4). PMID- 8469286 TI - Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. AB - To produce a vaccine against cancer, antigens must be found that are preferentially expressed by tumour cells and can induce an immune response against the tumour. The variable regions of the immunoglobulin molecules expressed on malignant B cells (idiotypes) are tumour-specific, but are weak immunogens. To induce an immune response in animals or humans, the idiotypic protein has therefore to be chemically coupled to a strongly immunogenic protein and mixed with an adjuvant. The resulting response can protect animals from subsequent tumour challenge, and cure animals with established tumours in combination with chemotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) augments antigen presentation in a variety of cells. Here we show that by fusing a tumour-derived idiotype to GM-CSF, it can be converted into a strong immunogen capable of inducing idiotype-specific antibodies without other carrier proteins or adjuvants and of protecting recipient animals from challenge with an otherwise lethal dose of tumour cells. This approach may be applicable to the design of vaccines for a variety of other diseases. PMID- 8469287 TI - Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. AB - Viruses that are non- or poorly cytopathic have developed various strategies to avoid elimination by the immune system and to persist in the host. Acute infection of adult mice with the noncytopathic lymphocytic choriomeningitis virus (LCMV) normally induces a protective cytotoxic T-cell response that also causes immunopathology. But some LCMV strains (such as DOCILE (LCMV-D) or Cl-13 Armstrong (Cl-13)) derived from virus carrier mice tend to persist after acute infection of adult mice without causing lethal immunopathological disease. Tendency to persist correlates with tropism, rapidity of virus spread and virus mutations. We report here that these LCMV isolates may persist because they induce most of the specific antiviral CD8+ cytotoxic T cells so completely that they all disappear within a few days and therefore neither eliminate the virus nor cause lethal immunopathology. The results illustrate that partially and sequentially induced (protective) immunity or complete exhaustion of T-cell immunity (high zone tolerance) are quantitatively different points on the scale of immunity; some viruses exploit the latter possibility to persist in an immunocompetent host. PMID- 8469288 TI - Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. AB - Dendritic cells, a minor cell population in lymphoid tissues, are specialized for presentation of antigenic peptides to T lymphocytes. Thymic dendritic cells are involved in the deletion of self-reactive T lymphocytes. Although all dendritic cells are ultimately of bone-marrow origin, it has not been clear whether thymic dendritic cells are produced in the adult thymus from a precursor cell or whether they migrate there preformed from the periphery. Recently we isolated from adult mouse thymus a population of early T precursors that could still form B lymphocytes, but not erythroid or myeloid cells, when transferred intravenously. Here we show that these thymic lymphoid precursor cells, as well as bone-marrow haematopoietic stem cells, are able to form both dendritic cells and T-cell progeny when transferred into an irradiated thymus. Such linked development may ensure that developing T cells are negatively selected predominantly by self antigens presented on newly formed thymic dendritic cells. PMID- 8469289 TI - Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2. AB - The nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha- and beta-globin locus control regions and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase). The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors. This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages. The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk). Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption. Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles. The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein. Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta thalassaemic (Hbbd-th3/Hbbd-th3) mice. We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly. PMID- 8469290 TI - Projection structure of rhodopsin. AB - Light absorption by the visual pigment rhodopsin triggers, through G-protein coupling, a cascade of events in the outer segment of the rod cell of the vertebrate retina that results in membrane hyperpolarization and nerve excitation. Rhodopsin, which contains 348 amino acids, has seven helices that cross the disk membrane and its amino terminus is extracellular. A wealth of biochemical data is available for rhodopsin: 11-cis retinal is bound to lysine 296 in helix VII; glutamic acid 113 on helix III is the counterion to the protonated Schiff's base; a disulphide bridge, cystine 110-187, connects helix III to the second extracellular loop e2 (refs 13, 14); the carboxy terminus has two palmitoylated cysteines forming a cytoplasmic loop i4 (ref. 15); three intracellular loops i2, i3 and i4 mediate activation of the heterotrimeric G protein transducin; glutamic acid 135 and arginine 136 at the cytoplasmic end of helix III affect binding of transducin. But to provide a framework to interpret these data, not only for rhodopsin but for other G-protein-coupled receptors, requires the structure to be determined. Here we present a projection map of rhodopsin showing the configuration of the helices. PMID- 8469291 TI - Roster. North Carolina Medical Society. 1992-1993. Officers, committees, commissions and roster of members. Alphabetical listings and roster by specialties within counties. PMID- 8469292 TI - [Insurance medicine assessment of provisions and housing adaptation in chronic disease]. PMID- 8469293 TI - [Multiresistant tuberculosis: a hazard for public health?]. PMID- 8469294 TI - ['Lorenzo's oil']. PMID- 8469295 TI - [A new chapter in the history of tuberculosis]. PMID- 8469296 TI - [Multiresistant tuberculosis: a new form of an old disease]. PMID- 8469297 TI - [Current regulations for provisions for the handicapped]. PMID- 8469298 TI - [Extra-intestinal infections caused by Vibrio spp. in The Netherlands]. AB - Six patients with serious cellulitis or ear infection due to Vibrio vulnificus, V. parahaemolyticus or V. alginolyticus are described. Four patients were infected during the summer in the Netherlands and two outside the Netherlands. Contact with seawater was the most probable source in four patients. In two patients the infection, caused by V. vulnificus, was transmitted by eel. This is a new way of transmission. PMID- 8469299 TI - [Case control study of the relationship between local environmental factors and hematopoietic malignancies in young subjects in Aalsmeer]. AB - In Aalsmeer, a horticultural community near the main international airport in the Netherlands, an incidence of haematopoietic malignancies in young people over four times the national mean was observed in the period 1980-1985. A population based case-control study investigated the association with local environmental factors. For each case younger than 40 years of age (n = 14), diagnosed between 1975 and 1989, four controls, matched for age and gender, were selected via local general practitioners. All parents of patients and controls completed a questionnaire on their life style, living conditions and health for several years preceding each individual diagnosis. Odds ratios (ORs) were calculated, matched and--if necessary--stratified for neighbourhood. Increased ORs were recorded for intensive use of petroleum products and pesticides, by the patients themselves and their fathers (OR petroleum products: 8.0, resp. 9.0; OR pesticides: 6.0, resp. 3.2). Most of these increases were statistically significant. Swimming in a local pond was also significantly associated with the disease (OR = 5.3); in the seventies this pond had been polluted by accidents with petroleum products and pesticides. contributed to the increase of the disease: ORs for several indirect exposure parameters were all above 2. It can be concluded that the increased incidence of childhood haematopoietic malignancies in Aalsmeer may have been associated with several specific local environmental factors. However, interpretation of the results should take into account that confidence intervals were wide, due to the necessarily limited number of cases. PMID- 8469300 TI - [Amyloidosis as cause of severe abdominal symptoms in a young Somali immigrant?]. AB - Extensive deposition of amyloid was detected in the digestive tract of a Somali woman aged 20 yr with abdominal pain, diarrhoea and cachexia. Immunohistochemical characterisation showed that the amyloid protein involved was of the AA type. Elevated levels were also found for serum amyloid A (SAA), an acute-phase protein which is the precursor of AA amyloid. The underlying inflammatory disease was peritoneal tuberculosis. The normalisation of the SAA levels and the recovery of the small intestine during tuberculostatic therapy showed that the tuberculosis was the cause of the enteropathy. This case report highlights the importance of early detection and effective treatment of the underlying inflammatory disease in case of AA amyloidosis. PMID- 8469301 TI - [Pneumococci]. PMID- 8469302 TI - GABAergic control of odor-induced activity in the frog olfactory bulb: electrophysiological study with picrotoxin and bicuculline. AB - In the olfactory bulb, the first relay of the olfactory pathways, GABA, could be largely involved in the information processing since the two main populations of interneurons, periglomerular and granular cells, use it as neurotransmitter through reciprocal synapses with second-order neurons. This study planned to clarify the role of GABAergic inhibition in odor coding and, more precisely, the role of glomerular GABAergic inhibition. To do so, we attempted to specifically block in vivo GABAA receptors with either picrotoxin or bicuculline. The drug was applied at the level of the glomerular layer so that the antagonist could act primarily via periglomerular cells. The analysis of the effects of blocking GABAA on the coding was studied by recording the second-order neuron responses to odor stimuli delivered in a wide concentration range. Under drug treatment, the second order neuron properties were deeply changed: response thresholds to odors were often lowered and spike bursts were more sustained in frequency and in duration. Thus, the GABAergic control on second-order neurons might be carried out by limiting the neuron excitability. GABAA antagonists applied in this manner could act to suppress the inhibitory effect of either the periglomerular cells or of the granule cells, both of which have been shown to contain enzymes for GABA production. The placement of the drug suggests to us that the action is primarily at the glomerulus. The results are consistent with periglomerular cells exerting a tonic inhibition on second-order neurons, an inhibition whose strength would be modulated by stimulus intensity. As a result, the amplifying role of glomerular convergence might be partly counterbalanced by input inhibition. Nevertheless, due to our procedure of drug application, one cannot rule out the possibility that the effects observed may partly reflect granular cell blocking. It can be concluded that the whole GABAergic inhibition, through GABAA receptors, permits a wide dynamic range of intensity coding. PMID- 8469303 TI - Effects of inferior olive inactivation and lesion on the activity of medial vestibular neurons in the rat. AB - In anaesthetized rats, the unitary activity from the medial vestibular nucleus had been recorded during horizontal sinusoidal rotation in the absence of visual stimulation. In the first series of experiments, the inferior olivary nuclei were selectively destroyed by means of 3-acetylpyridine. Unitary activity was recorded three to five days or one month after the lesion. A few days after the lesion, the average spontaneous activity, as well as the peak-to-peak amplitude of the modulation of the medial vestibular neurons during sinusoidal rotation, were significantly lower compared to those recorded in intact rats, and to those recorded one month after the lesion. In the second series of experiments, during reversible cooling of the inferior olive region of one side, in the contralateral medial vestibular nuclei 57% of units underwent a clear decrease in firing rate accompanied by a decrease in the amplitude of modulation. In rats whose inferior olivary nuclei had been destroyed by means of 3-acetylpyridine one month before, or whose cerebellum had been removed, there were few units that showed a decrease of the firing rate and modulation amplitude on cooling the same olivary region. Our experiments show that silencing the activity of the inferior olive causes a decrease both in the spontaneous firing rate and in the amplitude of the response of the vestibular neurons to natural labyrinthine stimulation. These results support the hypothesis that the inferior olive, by changing its firing rate, may regulate on-line the gain of reflexes which are under cerebellar control. PMID- 8469304 TI - Effects of noradrenaline on the firing rate of vestibular neurons. AB - The effects of microiontophoretic noradrenaline on the firing rate of neurons located in the vestibular complex have been studied in anaesthetized rats. Eighty five per cent of the neurons tested in all the vestibular nuclei modified their background firing rate upon noradrenaline application, generally by reducing it (86% of them). In few cases inhibitions were followed by a rebound. Responses were dose-dependent. No significant difference was found between vestibular neurons projecting to the spinal cord and those delivering their fibres to the oculomotor complex. Phentolamine, an alpha-adrenergic antagonist, blocked the noradrenaline-evoked inhibitions, whereas beta-adrenergic antagonist timolol was ineffective or enhanced them. Furthermore, responses were blocked by yohimbine, an alpha 2-adrenergic antagonist, and mimicked by clonidine, an alpha 2 adrenergic agonist, in the majority of neurons. In few cases prazosin, an alpha 1 adrenergic antagonist, was able to antagonize weak inhibitions and phenylephrine, an alpha 1-adrenergic agonist, to evoke an inhibitory effect blocked by prazosin. Isoproterenol, a beta-adrenergic agonist was totally ineffective on the neuronal firing rate. It is concluded that noradrenaline can modify the level of neuronal activity in the vestibular complex by acting mostly, but not exclusively, through alpha 2-adrenergic receptors. An influence of noradrenergic systems on the vestibular function by a direct action of noradrenaline inside the vestibular nuclei is proposed. PMID- 8469305 TI - Stable parkinsonian syndrome and uneven loss of striatal dopamine fibres following chronic MPTP administration in baboons. AB - The progressive degeneration of dopamine neurons observed in idiopathic Parkinson's disease was mimicked by injecting low doses of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) to baboons, on a chronic basis. Five Papio papio baboons were treated on two different regimens (chronic intravenous administration at weekly intervals for 20-21 months or, daily MPTP treatment for five days followed five to six months later by chronic weekly injections for 5 21.5 months). All animals were assessed for motor symptoms during and after neurotoxic treatment. Both regimens invariably resulted in the appearance of a progressive and irreversible syndrome characterized by action and resting tremor, cogwheel rigidity, postural impairments, hypokinesia and bradykinesia. In some animals, symptoms of resting tremor and rigidity initially restricted to one side of the body became bilateral within a few months of treatment. Subtle abnormalities that may be found in idiopathic Parkinson's disease such as alterations of the blink reflex response were also noted. Neuropathological examination of caudate nucleus, putamen, substantia nigra and ventral tegmental area in brain sections stained for tyrosine hydroxylase showed a typical uneven striatal dopamine fibre loss and a neuronal depletion in the dopaminergic mesencephalic cell groups that reproduce those observed in idiopathic Parkinson's disease. Immunocytochemical observations and behavioural data show that chronic rather than acute MPTP injection regimens can replicate most of the neuropathological and the clinical features typical of idiopathic Parkinson's disease, possibly by increasing the ability of this neurotoxin to target specific subpopulations of mesencephalic dopaminergic neurons. PMID- 8469306 TI - Dopamine-rich grafts in the neostriatum and/or nucleus accumbens: effects on drug induced behaviours and skilled paw-reaching. AB - This study compares the behavioural efficiency of dopaminergic mesencephalic neurons implanted into the rat neostriatum and/or the nucleus accumbens. The dopaminergic mesotelencephalic pathway was unilaterally destroyed by injection of 6-hydroxydopamine into the medial forebrain bundle at the level of the lateral hypothalamus. Three weeks later, embryonic dopaminergic mesencephalic neurons were implanted into the denervated neostriatum, or the nucleus accumbens or into both locations (double grafts). All animals were tested over a four month period for amphetamine- and apomorphine-induced rotation, apomorphine-induced locomotor activity, and on a skilled paw reaching task. The characteristic ipsilateral rotation induced by amphetamine observed in lesioned animals was significantly reduced by neostriatal and double grafts, but persisted in animals with grafts in the nucleus accumbens alone. Four months after grafting, an overcompensation of rotation was observed for the neostriatal and double grafted animals, which now rotated contralaterally, i.e. away from the grafted side. The rotation induced by apomorphine in lesioned rats was decreased by neostriatal and double grafts and to a lesser extent by grafts implanted into the nucleus accumbens. Apomorphine induced locomotor hyperactivity in lesioned animals was ameliorated by the nucleus accumbens and by double grafts. In the paw-reaching task, lesioned animals showed severe impairment in the use of the contralateral limb, which none of the grafts alleviated. Pretreatment with amphetamine had variable effects on the paw-reaching task which persisted in subsequent drug-free trials, suggesting that a conditioning mechanism may be involved. These findings suggest that the simultaneous reinnervation of the neostriatum and the nucleus accumbens by dopaminergic transplants is not sufficient to re-establish normal function in more complex behavioural tasks. PMID- 8469307 TI - Astrocytic messenger RNA responses to striatal deafferentation in male rat. AB - This investigation describes the schedule and regional distribution of astrocytic responses in striatum following deafferentation by unilateral frontal cortex ablation. In the ipsilateral deafferented striatum, glial fibrillary acidic protein and clusterin (sulfated glycoprotein-2) messengerRNA showed peak elevations by 10 days postlesioning (Northern blots). Vimentin messengerRNA responded faster, with a transient elevation by three days postlesioning. The messengerRNA for glial fibrillary acidic protein, clusterin and vimentin returned toward control levels by 27 days postlesioning. However, the neuronal marker growth-associated protein messengerRNA, was decreased at all postlesion times. By in situ hybridization, the increased glial fibrillary acidic protein messengerRNA and clusterin messengerRNA signals were localized mainly to the dorsal half of the ipsilateral deafferented striatum and followed the same schedule as found by Northern blots. Glial fibrillary acidic protein messengerRNA was widely diffused in the dorsal striatum and was excluded from fascicles of the internal capsule; a similar distribution was found for glial fibrillary acidic protein-immunopositive astrocytes. While clusterin messengerRNA signal showed a distinct clustering, its immunoreactivity appeared as deposits in the deafferented striatal neuropil; Western blots confirmed the immunocytochemical results. By in situ hybridization, vimentin messengerRNA was mostly localized to the cortical wound cavity dorsal to the deafferented striatum and overlapped the distribution of vimentin immunopositive cells. These findings suggest a coordination of striatal astrocytic messengerRNA responses with the degeneration of corticostriatal afferents. We also compared these same parameters with those from published reports on the hippocampus after deafferenting lesions. Certain astrocyte molecular responses to deafferentation are detected about five days earlier in the hippocampus than in the striatum. This different schedule in response to decortication may pertain to differences in synaptic remodeling in the hippocampus vs striatum. PMID- 8469308 TI - Nerve-dependent expression of high polysialic acid neural cell adhesion molecule in neurohypophysial astrocytes of adult rats. AB - The adult hypothalamo-neurohypophysial system of the rat retains the capacity to express highly polysialylated isoforms of neural cell adhesion molecule normally expressed in developing tissues. Here we report that the expression of these isoforms in neurohypophysial astrocytes (pituicytes) may be regulated by neurosecretory cells. In the intact neurohypophysis a strong and homogeneously distributed immunostaining for the "embryonic", highly sialylated form of neural cell adhesion molecules was detected by light-microscopic immunocytochemistry. By electron-microscopy, both neurosecretory axons and pituicytes were immunoreactive for this isoform. However, in contrast to the rather uniform staining on nerve fibres, polysialic acid immunolabelling on glial surfaces was uneven: immunostaining could be observed on glial surfaces facing neuronal elements, but not at contact sites between pituicytes. In addition, most glial and neuronal elements were heavily and evenly labelled with the polyclonal antibody recognizing "total" neural cell adhesion molecule. Surgical transection of the hypophysial stalk, a procedure that eliminates descending neurosecretory axons from the neurohypophysis, resulted in the complete disappearance of polysialic immunoreactivity from the neurohypophysis. The electron-microscopic analysis confirmed that cell surfaces of pituicytes lacked this immunoreactivity after the lesion. When residual neurosecretory axons were observed following an incomplete lesion, immunoreactivity on axons and glial processes was maintained. Transection did not affect the distribution of "total" neural cell adhesion molecule. We postulate that the presence of neurosecretory axons in the neurohypophysis is necessary to maintain the capacity of pituicytes to express immunoreactivity for the polysialylated isoforms of neural cell adhesion molecule but not the neural cell adhesion molecule itself since immunoreactivity for "total" neural cell adhesion molecule was unaltered after hypophysial stalk transection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469309 TI - Persistent degenerative state of non-pyramidal neurons in the CA1 region of the gerbil hippocampus following transient forebrain ischemia. AB - Morphological changes in the neurons of the gerbil hippocampus following 5 min of forebrain ischemia were examined using light and electron microscopy. Although non-pyramidal neurons in the CA1 region of the hippocampus survived through the full length of the observation period, up to six weeks after ischemia, they consistently demonstrated degenerative changes distinct from those of the well known "delayed neuronal death" of CA1 pyramidal cells. When examined with the light microscope, CA1 non-pyramidal neurons were found to be shrunken and their nuclei and cytoplasm were hyperchromatic between seven days and six weeks after ischemia. When examined with the electron microscope, postischemic non-pyramidal neurons were found to have markedly electron-dense profiles; their cytoplasm contained numerous free ribosomes and heterogeneous smaller granular substances, the latter also filling the nuclei. However, there was no loss of ribosomes from the rough endoplasmic reticulum, and mitochondrial cristae were preserved, suggesting that these neurons were viable. CA1 non-pyramidal neurons were studied immunohistochemically using three types of monoclonal antibodies, one each against parvalbumin, a nonphosphorylated epitope on the 168,000 mol. wt and 200,000 mol. wt subunits of neurofilament proteins, and microtubule-associated protein 2. CA1 non-pyramidal neurons lost immunoreactivity to these neuron specific substances six weeks after ischemia, suggesting that these degenerating cells lacked certain types of normal neuronal activity. We conclude that non pyramidal neurons in the hippocampal CA1 region survive transient ischemia but undergo degenerative changes following complete loss of CA1 pyramidal cells. These changes may be due to depletion of presumptive target-derived trophic factors within the non-pyramidal neurons. PMID- 8469310 TI - Differential regional and cellular distribution of beta-amyloid precursor protein messenger RNAs containing and lacking the Kunitz protease inhibitor domain in the brain of human, rat and mouse. AB - The beta-amyloid precursor protein is the precursor of the main component of senile plaques (the beta-amyloid peptide or beta/A4) found in the brain of aged humans and, in higher amounts, in the brain of Alzheimer's disease and Down's syndrome subjects. Four different forms of beta-amyloid precursor protein messenger RNAs have been described in humans and rodents: beta-amyloid precursor protein 695, beta-amyloid precursor protein 714, beta-amyloid precursor protein 751 and beta-amyloid precursor protein 770 messenger RNAs (numbers corresponding to the number of encoded amino acids). The two latter forms are characterized by containing in their sequence a region with high homology to the Kunitz family of serine protease inhibitors. We have used oligonucleotide probes to study the distribution of the different messenger RNAs encoding each of the four beta amyloid precursor proteins by in situ hybridization histochemistry in human, rat and mouse brain. We found that beta-amyloid precursor protein 695, beta-amyloid precursor protein 714 and beta-amyloid precursor protein 751 messenger RNAs were widely distributed in the human, rat and mouse brain and that their distribution was roughly similar in most brain areas in these three species. The distribution of beta-amyloid precursor protein 770 messenger RNA was not so wide and differed among the three species studied. beta-amyloid precursor protein 751 and 770 messenger RNAs were the only forms present at significant levels in rodent choroid plexus and meninges, while beta-amyloid precursor protein messenger RNA isoforms containing and lacking the Kunitz domain were detected in the human choroid plexus. We also observed that the relative levels of beta-amyloid precursor protein 751 and 770 messenger RNAs in the rat cerebral white matter as well as in the mouse and human striatum were higher than those of the beta amyloid precursor protein messenger RNAs lacking the Kunitz domain. While the most abundant beta-amyloid precursor protein messenger RNAs in the brain of all three species under study were, in descending order, beta-amyloid precursor protein 695 and beta-amyloid precursor protein 751 messenger RNAs, the least abundant form was not the same for all species: in human it was beta-amyloid precursor protein 714 messenger RNA and in rat and mouse brain it was beta amyloid precursor protein 770 messenger RNA. Our results show differences both inter- and intraspecies of the relative abundance and distribution of four beta amyloid precursor protein messenger RNAs in rat, mouse and human brain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8469311 TI - Primate nucleus basalis of Meynert p75NGFR-containing cholinergic neurons are protected from retrograde degeneration by the ganglioside GM1. AB - The effects of unilateral devascularizing lesions of the neocortex in primates (Cercopithecus aethiops) on the immunoreactivity of choline acetyltransferase and the low-affinity nerve growth factor receptor (p75NGFR) were investigated in cell bodies of the nucleus basalis of Meynert. Choline acetyltransferase enzymatic activity was measured in the dissected ipsi- and contralateral nucleus basalis of Meynert as well as in the remaining cortex adjacent to the lesion. Cortically lesioned animals displayed a shrinkage of p75NGFR-immunoreactive cholinergic cell bodies in only the intermediate portion of the nucleus basalis of Meynert as well as a depletion of choline acetyltransferase activity in this cellular complex. In contrast, cortically lesioned monkeys treated with monosialoganglioside did not reveal a significant loss of choline acetyltransferase activity or shrinkage of nucleus basalis of Meynert cholinergic neurons, but rather a modest hypertrophy. These results are discussed in relation to a possible use of putative trophic agents in the repair of the damaged central nervous system. PMID- 8469312 TI - Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease. AB - We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID- 8469313 TI - Oxytocin and vasopressin release within the supraoptic and paraventricular nuclei of pregnant, parturient and lactating rats: a microdialysis study. AB - The release of the nonapeptides oxytocin and vasopressin within the hypothalamic supraoptic and paraventricular nuclei was measured in 30-min microdialysates in conscious female rats in the last three days of pregnancy, during parturition, immediately after parturition and during suckling, all in the same rats, and in virgin controls. Nonapeptide release within the supraoptic and paraventricular nuclei was unchanged during late pregnancy compared to virgin rats, but intranuclear oxytocin and not vasopressin release was elevated during parturition (relative to late pregnancy, supraoptic nucleus: to 254%, paraventricular nucleus: to 300%; P < 0.01) and during suckling also on days 8-10 of lactation (relative to pre-suckling, supraoptic nucleus: to 407%, paraventricular nucleus: to 275%; P < 0.02). Suckling-induced release of oxytocin was significantly reduced using Ca(2+)-free, EDTA-containing (10(-4) M) microdialysis fluid and further stimulated by high K(+)- (56 mM), veratridine-containing (50 microM) microdialysis fluid. The opioid antagonist naloxone whether given by subcutaneous injection (5 mg/kg) or directly into the supraoptic nucleus by microdialysis (5 x 10(-6) M) or microinjection (1.5 microliters, 10(-6) M) did not further enhance oxytocin release within either the supraoptic or paraventricular nuclei during parturition. In contrast to the selective release of oxytocin within the supraoptic and paraventricular nuclei during parturition and suckling, direct osmotic stimulation of the nuclei by microdialysing hypertonic medium (artificial cerebrospinal fluid; 1 M NaCl) increased intranuclear release of both oxytocin and vasopressin which was further enhanced after replacement of hypertonic with isotonic fluid. This rebound phenomenon served to confirm the precise location of the microdialysis probe ante mortem and the ability of the nuclei to adequately respond to the osmotic stimulus at the end of the experiment. The study has shown that oxytocin is released in the supraoptic and paraventricular nuclei during parturition as well as in lactation unrestrained by endogenous opioids during parturition. This intranuclear release of oxytocin may act by local positive feedback stimulation of oxytocin neurons to excite further oxytocin release in the brain and into blood during both parturition and lactation. PMID- 8469314 TI - Oxytocin neuron activation and Fos expression: a quantitative immunocytochemical analysis of the effect of lactation, parturition, osmotic and cardiovascular stimulation. AB - As c-fos expression is generally thought to be linked to neuronal activation, we compared Fos immunoreactivity in identified oxytocinergic and vasopressinergic neurons of female rats under various conditions known to elicit particular patterns of electrophysiological and secretory activity in these neurons. In suckled lactating animals, Fos immunoreactivity was visible only in rare oxytocinergic and vasopressinergic neurons of the paraventricular and supraoptic nuclei, even after interruption of suckling for 18-72 h. On the other hand, many Fos-positive cells were visible in the nuclei of parturient rats; they involved about 25% of supraoptic oxytocinergic elements. Even more Fos-positive elements were visible in the nuclei of lactating rats that had also undergone 24 h water deprivation or haemorrhage. This involved about 75% vasopressinergic neurons and 25% oxytocinergic neurons of the supraoptic nucleus. Fos immunoreactivity was particularly conspicuous in oxytocin neurons of the anterior commissural nucleus after haemorrhage. After water deprivation or haemorrhage, Fos-positive oxytocinergic neurons in the supraoptic nucleus were significantly more numerous in virgin rats than in lactating rats. Our observations show that suckling, although a most potent stimulus for oxytocin neuron activation and oxytocin release, is inefficient in inducing Fos synthesis in magnocellular neurons, even after a period of interruption. On the other hand, parturition, water deprivation and haemorrhage were more potent stimuli for both neurosecretory systems. However, under each type of stimulation, only part of the neuronal populations within each nucleus were Fos-positive, suggesting that different stimulus specific pathways are involved in these regulations. In so far as electrical activity is one possible mechanism for c-fos expression, comparison of the patterns of c-fos activation with the known electrophysiological behaviour of hypothalamic magnocellular neurons suggests that Fos synthesis in these neurons is linked to the number of action potentials generated over a period of time, more than to the pattern of electrical activity, whatever the physiological impact of this pattern. Furthermore, within a group of neurons, the heterogeneity of the response in terms of Fos synthesis may be correlated to the variability of the electrophysiological response within this group. PMID- 8469315 TI - Interferon beta in multiple sclerosis. PMID- 8469316 TI - Clinical neuromythology X. Faithful fashion: survival status of the brain transplant cure for parkinsonism. PMID- 8469317 TI - Medicare hospital utilization review for ischemic cerebrovascular disease. PMID- 8469318 TI - Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. AB - We report a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB) in 372 ambulatory patients with relapsing-remitting multiple sclerosis (MS). Entry criteria included an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 and at least two exacerbations in the previous 2 years. One-third of the patients received placebo, one-third 1.6 million international units (MIU) of IFNB, and one-third 8 MIU of IFNB, self-administered by subcutaneous injections every other day. The primary end points were differences in exacerbation rates and proportion of patients remaining exacerbation-free. The annual exacerbation rate for patients receiving placebo was 1.27; for 1.6 MIU IFNB, 1.17; and for 8 MIU IFNB, 0.84 after 2 years. Exacerbation rates were significantly lower in both treatment groups compared with the placebo group (8 MIU versus placebo, p = 0.0001; 1.6 MIU versus placebo, p = 0.0101; and 8 MIU versus 1.6 MIU, p = 0.0086), suggesting a dosage effect. The reduction in exacerbation severity in the 8 MIU group was attributable to a twofold reduction in the frequency of moderate and severe attacks. More patients in the 8 MIU group (n = 36) were exacerbation-free at 2 years compared with the placebo group (n = 18; p = 0.007). EDSS scores changed little from baseline in both the placebo and treatment arms. Accordingly, a significant change in disability could not be discerned in this trial. Finally, in serial MRIs, MS activity was significantly less in the high-dose IFNB group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469319 TI - Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. AB - We performed yearly MRI analyses on 327 of the total 372 patients in a multicenter, randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNB). Clinical results are presented in the preceding companion paper. Baseline MRI characteristics were the same in all treatment groups. Fifty-two patients at one center formed a cohort for frequent MRIs (one every 6 weeks) for analysis of disease activity. The MRI results support the clinical results in showing a significant reduction in disease activity as measured by numbers of active scans (median 80% reduction, p = 0.0082) and appearance of new lesions. In addition, there was an equally significant reduction in MRI-detected burden of disease in the treatment as compared with placebo groups (mean group difference of 23%, p = 0.001). These results demonstrate that IFNB has made a significant impact on the natural history of MS in these patients. PMID- 8469320 TI - Levodopa, melanoma, and Parkinson's disease. AB - Previous reports and the Physicians' Desk Reference caution against the use of levodopa in Parkinson's disease (PD) patients with melanoma. A critical review of the literature reveals only anecdotal evidence to support a link between levodopa and melanoma. In fact, levodopa has an antitumor effect on melanoma. We report nine patients with PD and melanoma who were treated with levodopa/carbidopa (L/C). Current evidence suggests that L/C can be used safely in PD patients with a history of melanoma. PMID- 8469321 TI - Clinical experience with controlled-release carbidopa/levodopa in Parkinson's disease. AB - We converted 158 Parkinson's disease (PD) patients on stable doses of standard carbidopa/levodopa (Std-L) to controlled-release carbidopa/levodopa (L-CR). Of the 141 patients who completed the study, 103 (73%) preferred L-CR, 26 (18.5%) preferred Std-L, and 12 (8.5%) had no preference. One hundred fourteen patients elected to continue L-CR, and we performed the primary data analysis on this group. Following conversion to L-CR, patients reported an increase in length of benefit from each dose and an increased "kick-in" time. There was a decrease in the total number of doses, "off" periods, sleep interruptions per night, dose failures, and sleep disturbances. Conversion to L-CR resulted in a significant increase in total levodopa dose. There was no significant change in the dyskinesias. However, early-morning dystonia resolved in eight of 14 patients. Our findings suggest that L-CR is particularly effective in decreasing motor fluctuations, reducing nocturnal problems, and minimizing levodopa dose failures in PD. PMID- 8469322 TI - Magnetic resonance imaging in childhood intractable partial epilepsies: pathologic correlations. AB - We conducted a retrospective single-blind study assessing the value of MRI in 44 children surgically treated for partial epilepsy, and correlated the MRI findings with the pathology in all cases. MRI revealed abnormalities in concordance with the clinical and electroencephalographic data in 84% of patients. Developmental neuronal migration pathology was present in 25% of patients and was relatively more common in the sensorimotor cortex. There was hippocampal sclerosis in 50% of patients with temporal lobe resection; however, only two of the 10 children with hippocampal sclerosis were below the age of 12 years. Similarly, ganglio-glial tumors were more common than astrocytomas in children below age 12. These results indicate that MRI is sensitive in the detection of pathologic abnormalities in most pediatric candidates for epilepsy surgery, and that the distribution and type of pathology appear to be age related in this population. PMID- 8469323 TI - Felbamate monotherapy for partial-onset seizures: an active-control trial. AB - We evaluated felbamate (FBM) monotherapy in 111 patients with uncontrolled partial-onset seizures in a multicenter, double-blind, parallel-group trial. During the 56-day baseline period, patients had at least eight partial-onset seizures and received one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients received either FBM 3,600 mg/d or valproate (VPA) 15 mg/kg/d. The baseline AED at therapeutic levels was discontinued by one-third decrements on study days 1, 14, and 28 and the sub-therapeutic AED, if any, was discontinued completely on study day 1. Study endpoints were completion of 112 study days or fulfilling one or more escape criteria. Criteria for escape relative to baseline were (1) twofold increase in monthly seizure frequency, (2) twofold increase in highest 2-day seizure frequency, (3) single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or (4) significant prolongation of GTCs. The primary efficacy variable was the number of patients in each treatment group who met escape criteria. Thirty-seven patients on VPA and 18 on FBM met escape criteria (p < 0.001). Even when we considered FBM dropouts to have fulfilled escape criteria and VPA dropouts to have completed the 112-day trial, the treatment difference remained statistically significant (p = 0.039) in favor of FBM. Adverse experiences with FBM were all mild or moderate in severity. The frequency of adverse experiences was much lower during monotherapy. FBM monotherapy was effective in the treatment of partial-onset seizures with or without secondarily generalized seizures and demonstrated a favorable safety profile. PMID- 8469324 TI - Felbamate: a double-blind controlled trial in patients undergoing presurgical evaluation of partial seizures. AB - We studied the efficacy and safety of felbamate, an investigational antiepileptic drug, in a unique, double-blind, placebo-controlled trial. Sixty-four patients with refractory partial-onset seizures who completed a routine evaluation for epilepsy surgery met seizure frequency entry criteria. Each patient received felbamate or placebo in addition to the anticonvulsant regimen present at the conclusion of the presurgical evaluation. The treatment phase consisted of an 8 day inpatient period and a 21-day outpatient period. The efficacy variable was time to fourth seizure. The difference in time to fourth seizure was statistically significant (p = 0.028) in favor of felbamate. Eighty-eight percent of the patients in the placebo group had a fourth seizure during the treatment phase compared with 46% of the patients in the felbamate group (p = 0.001). Adverse experiences with felbamate were generally mild or moderate in severity. This trial demonstrated the ability of felbamate to quickly and safely reduce the occurrence of frequent partial-onset seizures and maintain effective seizure control following reductions in the dosages of standard antiepileptic drugs. PMID- 8469325 TI - T2 relaxation time in patients with Parkinson's disease. AB - Postmortem studies of patients with Parkinson's disease (PD) reveal an increase in iron concentration in the substantia nigra. Iron content in the brain is associated with decreased signal intensity on T2-weighted MRI. We measured in vivo the T2 relaxation time in 30 PD patients and 33 healthy volunteer subjects, using a 1.5-T whole-body MRI system. In comparison with healthy controls, T2 values in PD patients were reduced in the following brain regions: substantia nigra, caudate nucleus, and putamen. Due to the overlap between patients and control subjects, we could not differentiate, in a given patient, healthy from diseased state on the basis of T2 relaxation time. Our findings support the notion of increased iron deposition in the substantia nigra of patients with PD. However, the shortening of T2 values in the substantia nigra did not correlate with disease duration nor with clinical severity. PMID- 8469326 TI - Sleep state and the risk of seizure recurrence following a first unprovoked seizure in childhood. AB - In a prospective study, we have followed 347 children identified at the time of a first unprovoked seizure for a mean of 46 months. To date, 135 (39%) have experienced a seizure recurrence. In this study, we analyzed recurrence risk as a function of whether the child was asleep or awake at the time of the first seizure. The cumulative recurrence risks for children whose first seizure occurred in sleep was 28% at 0.5 years, 39% at 1 year, 53% at 2 years, and 55% at 4 years, compared with recurrence risks of 18%, 23%, 30%, and 35% at the same intervals in children whose first seizure occurred while awake (p < 0.001). The association of a first seizure during sleep with an increased recurrence risk was present primarily in children with idiopathic seizures. It occurred in both those with a normal and an abnormal EEG. On multivariable analysis, sleep state, etiology, and the EEG were statistically significant predictors of recurrence risk. In children who experienced a seizure recurrence, the recurrences occurred in the same sleep state in 73% of the cases (p < 0.0001). This was also true of subsequent recurrences. We conclude that the occurrence of a first seizure in sleep is associated with an increased risk of recurrence. Subsequent seizures, if they do occur, usually occur in the same sleep state as the initial seizure. PMID- 8469327 TI - Material-specific memory in the intracarotid amobarbital procedure. AB - We examined material-specific memory in 45 left hemisphere language dominant patients with temporal complex partial seizures (24 right, 21 left) during the intracarotid amobarbital procedure (IAP) by showing eight cards displaying two line drawings of common objects, two printed words, one colored shape, one math expression, one face, and one abstract shape following amobarbital injection (mean = 109.9 mg). We assessed delayed recall and recognition following clearing. Patients with right foci recognized significantly fewer verbally mediated stimuli (words, object drawings, colored shape) with left than with right injection. Patients with left foci recognized a nonverbal stimulus (abstract shape) more poorly following right versus left injection. Discriminant function analysis lateralized 85% of the sample from memory predictors, upheld to 81% on crossvalidation. Material-specific memory remains intact in the hemisphere contralateral to a seizure focus, but wider representation may occur for stimuli normally dominant for the hemisphere with the seizure focus. The IAP significantly lateralizes a seizure focus with use of both types of stimuli. PMID- 8469328 TI - Clinical course of spontaneous subarachnoid hemorrhage: a population-based study in King County, Washington. AB - Over 2 years, we identified 171 patients in King County, Washington, experiencing an incident subarachnoid hemorrhage and characterized their clinical course and outcome. Most (65%) were women and most (68%) were under age sixty-five. Only five died without medical attention. The remaining 166 patients were hospitalized and had CTs of the head. Of these, 103 underwent aneurysm surgery, 40 developed acute hydrocephalus, 32 had symptomatic vasospasm, and 30 re-bled. Sixty-eight percent (68%) survived to 1 month after the bleed and 62% to 1 year. Independent predictors of good recovery by 1 month after the bleed included youth, a high score on the admission Glasgow Coma Scale, and absence of blood on the first CT. In this population-based series, at 1 month after the bleed, approximately one third of patients were dead, one-third had neurologic deficits, and one-third were doing well. PMID- 8469329 TI - MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy. AB - We performed MRI volumetric measurements of the amygdala (AM), the hippocampal formation (HF), and the anterior temporal lobe in a group of 30 patients with intractable temporal lobe epilepsy (TLE) and in seven patients with extratemporal lobe foci. Measurements were analyzed with a semiautomated software program and the results compared with those of normal controls and correlated with the findings of all other investigations. In particular, we compared the results with the lateralization of epileptic abnormalities in the EEG. Volumetric studies of AM and HF showed lateralization of measurable atrophy consistent with that derived from extracranial and intracranial EEG examinations. The HF volumes were more sensitive and provided a lateralization in 87%. Combined measurements of AM and HF showed lateralization in 93%, always congruent with the results of EEG lateralization. This slight but important additional improvement in discrimination justifies using AM measurements in MRI volumetric studies of mesial temporal structures. Volumetric studies combined with other currently employed noninvasive techniques may diminish the need for invasive methods of investigation in patients with TLE. PMID- 8469330 TI - Facial asymmetry, hippocampal pathology, and remote symptomatic seizures: a temporal lobe epileptic syndrome. AB - We performed a prospective study of neuroimaging studies and temporal lobe pathology in 13 patients with facial asymmetry and intractable partial epilepsy of temporal lobe origin. The 13 patients, derived from 50 consecutive patients with nonlesional medically refractory partial epilepsy, were deemed appropriate candidates for an anterior temporal lobectomy. The facial weakness occurred exclusively, or was most prominent, during emotional expression, ie, spontaneous smiling. The temporal lobe of seizure origin, demonstrated by ictal long-term EEG monitoring, was always contralateral to the side of weakness. All 13 patients had a history of early childhood neurologic disease, eg, complex febrile seizure or bacterial meningitis. Hippocampal formation atrophy was present in all the epileptic temporal lobes by MRI-based volume studies. Twelve of the 13 patients subsequently received an anterior temporal lobectomy, and mesial temporal sclerosis was present in all the surgically excised temporal lobes. Ten of the 12 patients have been seizure-free during short-term follow-up. Facial asymmetry may occur in patients with partial epilepsy related to remote symptomatic seizures and mesial temporal sclerosis. PMID- 8469331 TI - Brain infarction severity differs according to cardiac or arterial embolic source. AB - We compared clinical and radiologic features between 246 cardiac embolism (EMB) and 66 arterial embolic (tandem arterial pathology [TAP]) patients selected from the 1,273 patients with cerebral infarction in the Stroke Data Bank. Diagnostic definitions accounted for the increased frequency of cardiac disease among patients with EMB compared with TAP (78.4% versus 29.3%), while transient ischemic attacks (32.3% versus 13.1%) and carotid artery bruit (15.1% versus 3.3%) were more prevalent in TAP than in EMB. Multiple logistic regression differentiated TAP and EMB further. The probability of a TAP diagnosis was increased by the CT finding of a superficial infarct alone (odds ratio [OR] = 4.6; 95% CI = 1.5 to 13.7) or by a higher admission hematocrit. The probability of EMB was greater in patients with an initial decreased consciousness (OR = 39.2; 95% CI = 4.0 to 381.3) or with an abnormal first CT (OR = 3.2; 95% CI = 1.2 to 8.6). These findings indicate that the two infarct subtypes differ in the location and extent of the cortical infarction, which argues for a smaller particle size, with smaller and more distal infarction in embolism from an arterial source compared with cardiogenic embolism. PMID- 8469332 TI - Selective dorsolateral frontal lobe dysfunction associated with diencephalic amnesia. AB - We report three cases with unilateral thalamic ischemic lesions that resulted in lasting material-specific memory impairments and concomitant selective frontal lobe-related cognitive deficits. In two cases the lesions were limited to the left thalamus, and in the third the right thalamus was involved. These deficits were associated with ipsilateral diencephalic, striatal, and dorsolateral prefrontal hypoperfusion. The damage implicated the ventral anterior nucleus, the mamillothalamic tract, and the rostroventral internal medullary lamina. These findings suggest that medial thalamic damage involving the ventral and rostral sector of the dorsal thalamus will concurrently affect functionally and neurally distinct limbodiencephalic pathways and diencephalic connections with the frontal cortex. A review of the neuropsychological and neuroimaging findings from previously reported cases with vascular lesions of the thalamus further supports this contention. The presence of frontal lobe-related cognitive deficits, though not obligatorily related to the memory problems, may contribute to some aspects of the memory deficits and affect the nature of the memory disorder observed in some cases with diencephalic amnesia. PMID- 8469333 TI - Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria: report of two cases. AB - We report the clinical, radiologic, and postmortem findings in two patients with paroxysmal nocturnal hemoglobinuria (PNH) who developed cerebral venous thromboses (CVTs). In contrast with those in most published cases, our patients did not have focal neurologic signs. Antemortem diagnosis of CVT had been made by MR cerebral venograms. We conclude that (1) PNH should be considered in any patient with stroke associated with iron deficiency anemia, hemolysis, hemoglobinuria, or hemosiderinuria; (2) PNH should be in the differential diagnosis of CVT; (3) the latter could present without focal neurologic signs; and (4) MR cerebral venography may be a reliable diagnostic alternative to cerebral angiography when CVT is suspected. PMID- 8469334 TI - Gelastic seizures and hypothalamic hamartomas: evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment. AB - We retrospectively studied 12 consecutive patients with gelastic seizures and hypothalamic hamartomas who, because of intractable epilepsy, underwent chronic intracranial EEG monitoring or epilepsy surgery. All patients had medically refractory seizures that included laughter as an ictal behavior (gelastic seizures). The hypothalamic hamartomas were identified with neuroimaging studies (12 of 12) and by pathologic verification (four of 12). Associated clinical features included behavioral disorders (n = 5), developmental delay (n = 4), and precocious puberty (n = 2). Interictal extracranial EEG predominantly showed bi hemispheric epileptiform changes suggesting a secondary generalized epileptic disorder. Intracranial EEG recordings, performed in eight patients, indicated the apparent focal onset of seizure activity (anterior temporal lobe [n = 7] and frontal lobe [n = 1]). None of the seven patients who underwent a focal cortical resection, however, experienced a significant reduction in seizure tendency. An anterior corpus callosotomy, performed in two patients with symptomatic generalized epilepsy, resulted in a worthwhile reduction in drop attacks. Results of this study may modify the surgical strategies in patients with gelastic seizures and hypothalamic hamartomas. PMID- 8469335 TI - The natural history of amyotrophic lateral sclerosis and the use of natural history controls in therapeutic trials. AB - We analyzed the natural history of amyotrophic lateral sclerosis in 277 patients. Our goal was to develop a better understanding of the clinical disease and thus improve the design of therapeutic trials. The Tufts Quantitative Neuromuscular Exam (TQNE) was used as the primary assessment instrument. Our analysis suggested that although more observations are desirable, six monthly TQNEs were adequate to establish the rate of disease progression. We observed a spectrum of deterioration rates without definable subgroups. The striking linearity of deterioration was confirmed. We found a high correlation between deterioration rates in arm and leg strength for individual patients, but a wide range between different patients. Sex and the age at clinical onset did not affect the deterioration rate. As compared with patients without a positive family history, those with other affected family members had a slower loss in arm but not leg strength. We propose that natural history controls can be used effectively in the design of ALS therapeutic trials. PMID- 8469336 TI - The fatigue of rapid repetitive movements. AB - Normal subjects (n = 7) performed rapid voluntary isometric contractions of the adductor pollicis and the tibialis anterior. Within the first minute of this low intensity exercise, the speed of tension development slowed, accompanied by a prolongation in EMG burst duration. In contrast, electrically evoked contractions either became more rapid (twitch) or did not change (tetanus), suggesting a fatigue of central origin. 31P NMR measurements of high-energy phosphates showed that the relationship between the fall of maximum force and changes of phosphates and pH was similar to that produced by other high-intensity fatiguing exercise protocols. Thus, rapid movements produce fatigue through two major mechanisms. First, there is slowing of the speed of tension development which appears secondary to central fatigue. Second, the decline of muscle force is primarily attributable to changes in muscle pH or inorganic phosphate, which usually occurs only after high-intensity (but non-rapid) exercise. PMID- 8469337 TI - Ventrolateral and dorsomedial somatosensory association cortex damage produces distinct somesthetic syndromes in humans. AB - Five somatosensory cortices have distinctive somatotopic representations, cytoarchitecture, and connectivity: primary somatosensory cortex (SI), ventrolateral association cortices (SII, SIII, and SIV), and dorsomedial association cortex (supplementary sensory area). Patients with focal lesions of ventrolateral (n = 5) and dorsomedial (n = 6) somatosensory association cortices (SACs) and hemiparetic (n = 8) and neurologically normal control patients (n = 14) underwent detailed somesthetic testing that encompassed basic, intermediate, and complex (tactile object recognition) somesthetic functions. Dorsomedial lesions acutely caused severe disruption of somesthetic processing and severe apraxia when the area of damage was extensive and involved anterior and posterior cortices. In contrast, ventrolateral lesions caused tactile agnosia. Chronically, sensorimotor function following dorsomedial damage improved considerably. Tactile agnosia following ventrolateral damage, however, was readily detectable for years following onset. Functional differences between ventrolateral and dorsomedial SACs may reflect parallel processing in dual somatosensory systems. PMID- 8469339 TI - Brain magnetic resonance imaging in coronary artery bypass grafts: a pre- and postoperative assessment. AB - We undertook a study to determine (1) the frequency and prognostic significance of preexisting MRI brain abnormalities in patients undergoing coronary artery bypass grafts (CABG) and (2) whether MRI can detect surgery-related brain damage in 31 neurologically asymptomatic CABG patients (mean age, 61.0 +/- 6.6 years). MRIs were performed within 7 days before and 8 to 17 days after surgery. When we compared the preoperative images with those of 31 age- and risk factor-matched neurologically asymptomatic controls free of cardiac disease (mean age, 60.3 +/- 6.1 years), higher rates of thromboembolic infarcts (16% versus 0%), lacunes (58.1% versus 32.3%), and brainstem lesions (22.6% versus 3.8%) were noted. Subjective rating demonstrated significantly larger ventricles in patients than in controls (p = 0.002). CABG candidates also had significantly increased ventricular-to-intracranial cavity ratios (VICR) as determined by semiquantitative volumetric measurements (6.9 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.0004). Eleven patients had postsurgical complications, with eight having symptoms consistent with diffuse encephalopathy. The only MRI finding that separated encephalopathic from complication-free patients was ventricular size (VICR 9.0 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.006). This difference remained statistically significant after adjustment for the effects of age (p = 0.04). Postoperative MRI consistently failed to demonstrate surgery-related brain damage responsible for the encephalopathy. PMID- 8469338 TI - HLA-DPB1 allele associates with early-onset myasthenia gravis in Japan. AB - We investigated the HLA-DPB1 allele in 43 unrelated Japanese patients with myasthenia gravis (MG) using digestion of polymerase chain reaction (PCR) amplified DNA with allele-specific restriction endonucleases (PCR-RFLP method). We found a higher frequency of the DPB1*0201 allele in female patients whose ages at onset were less than 30 years (83.3%) than in controls (35.6%). The study also included serologic typing of HLA-A, -B, -C, and -DR antigens in 72 patients with MG, and confirmed previous results demonstrating a strong association of HLA-DR53 with early onset of MG in females. These results indicate that both the DPB1*0201 allele and DR53 play key roles in the disease process of MG in early-onset females, and that the genetic background of Japanese females with early-onset MG is different from that of other patients with MG. PMID- 8469340 TI - Auditory system degeneration in Alzheimer's disease. AB - We observed a highly topographically specific and consistent pattern of degeneration in the auditory system of Alzheimer's disease (AD) patients. Senile plaques (SP) and neurofibrillary tangles (NFT) were distributed throughout the ventral nucleus of the medial geniculate body (MGB) and the central nucleus of the inferior colliculus (IC) in nine of nine AD patients. Adjacent nuclei within the MGB and IC were consistently spared. NFT and SP were also present in the primary auditory and the auditory association cortices. In all control tissues, there were neither SP nor NFT in any of the above sites. The cochlear nuclei were normal in tissues from both AD and control patients. The ventral nucleus of the MGB is the major thalamic relay station for auditory function and receives fibers from neurons of the central nucleus of the IC, with projections arranged tonotopically in a laminar pattern corresponding to a gradient of high-to-low frequency ranges. The degenerative changes distributed throughout these nuclei suggest that neuronal loss may include all frequency ranges in AD. In contrast, the clinical features of presbycusis in elderly patients include only high frequency loss due to lesions peripherally in the cochlea or auditory nerves, rather than in the central auditory nuclei. These histologic changes in the brains of AD patients may provide an additional basis for altered cognitive function due to primary sensory deafferentation. PMID- 8469341 TI - Polyglucosan body disease simulating amyotrophic lateral sclerosis. AB - We describe two patients with polyglucosan body disease (PBD) with the clinical features of atypical amyotrophic lateral sclerosis (ALS). Patient 1 was demented, and patient 2, of Ashkenazi background, was incontinent of urine. Autopsy of patient 1 revealed diffuse CNS accumulations of polyglucosan bodies (PB) localized primarily in neuronal and astrocytic processes and rarely in neuronal perikarya. PB were present in peripheral nerve and myocardium. Brancher enzyme analysis of nerve and muscle was normal. Patient 2's sural nerve biopsy showed PB. Brancher activity was markedly reduced in nerve but not in leukocytes. Previous reports have shown reduced leukocyte brancher activity in Ashkenazi patients with PBD. Clinically, pathologically, and biochemically, PBD is heterogeneous and may include patients presenting with ALS. Cases in which typical pathologic features of PBD are combined with findings of rare PB in neural perikarya may represent a pathologic variant of PBD. Brancher enzyme activity may be normal or only mildly reduced in leukocytes in Ashkenazi patients with PBD, implying genetic heterogeneity. PMID- 8469342 TI - Kennedy's disease: a clinicopathologic correlation with mutations in the androgen receptor gene. AB - We confirmed a mutation of the androgen receptor gene as the cause for Kennedy's disease, also called "X-linked recessive spinal and bulbar muscular atrophy" or "bulbospinal neuronopathy." The mutation is characterized by an increased size of a polymorphic tandem CAG repeat within the first exon of the gene. The study population consisted of 17 patients from seven families (five distinct kinships and two isolated cases). Two patients were as yet asymptomatic and had normal examinations. Four carrier females showed the mutant as well as the normal allele; none showed clinical features of Kennedy's disease. There was no large expansion of the mutation observed in three generations of one family. Phenotypic expression between and within families was variable and not related to the size of the mutation. This contrasts with the gene mutations found in myotonic dystrophy and fragile X syndrome, where increased severity of disease correlates with the number of tandem triplet repeats. The findings reported here appear to explain the failure to find genetic anticipation in Kennedy's disease. The DNA test for Kennedy's disease can now be used for definitive diagnosis and carrier detection. In addition, mutation analysis allows early detection, which has implications for potential treatment. PMID- 8469343 TI - Duchenne muscular dystrophy: deficiency of dystrophin-associated proteins in the sarcolemma. AB - Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a major component of the subsarcolemmal cytoskeleton and exists in a large oligomeric complex tightly associated with several sarcolemmal glycoproteins which provide a linkage to the extracellular matrix protein, laminin. In the present study, we investigated the status of the dystrophin-associated proteins in the skeletal muscle from 17 DMD patients of various ages. The results revealed a dramatic reduction in all of the dystrophin-associated proteins in the sarcolemma of DMD muscle compared with normal muscle and muscle from a variety of other neuromuscular diseases. This abnormality was common in all 17 DMD patients, irrespective of age. Our results indicate that the absence of dystrophin leads to the loss in all of the dystrophin-associated proteins, which renders DMD muscle fibers susceptible to necrosis. The analysis of dystrophin-associated proteins is important in the assessment of experimental therapies that attempt to replace dystrophin in DMD muscle. PMID- 8469344 TI - Altered brain development in Turner's syndrome: an event-related potential study. AB - We compared event-related brain potentials (ERPs) and reaction time (RT) measures from untreated young (prepubertal and peripubertal; ages 9 to 14) and old (postpubertal; ages 15 to 20) Turner's syndrome (TS) subjects with those from normal age-matched controls. Comparisons among groups permitted the assessment of the relative roles of congenital and maturational brain alterations as possible bases of the cognitive deficits in TS. All subjects were presented with series of auditory stimuli, and they either counted one of the two stimuli or made rapid discriminative button presses to both. The results indicated that, whereas the ERPs in young TS females were essentially the same as those in their age-matched controls, the ERPs in old TS females more closely resembled those in both young groups than those in their age-matched controls. Specifically, a late (400 to 900 msec) frontal negative slow wave (Nc) in the old TS subjects failed to show the normal maturational course in which the amplitude and duration of this component steadily decreases with age. Except for slightly greater amounts of N1 amplitude in the young TS group, the latencies, amplitudes, and scalp distributions of the other ERP components (N1, P2, N2, P300) were all the same at all ages in the TS subjects and their controls. Behaviorally, both TS groups had longer RTs than their controls but, consistent with the ERP results, they did not make more errors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469346 TI - Myopathy in the elderly: evaluation of the histopathologic spectrum and the accuracy of clinical diagnosis. AB - We undertook a retrospective clinicopathologic study to ascertain the spectrum of histopathologic muscle biopsy changes in the elderly thought to have a myopathy, and to determine the accuracy of clinical diagnosis of myopathy in the elderly compared with a younger control population. We compared muscle histology and case histories, as well as EMG and creatine kinase (CK) data, obtained over 10 years from 77 consecutive patients aged 65 years or older (75 +/- 6, mean +/- SD; group 1) with those from 104 patients aged 30 to 50 years (group 2). Prominent myopathic features were present in 42% (group 1) versus 51% (group 2) of all biopsies. Neurogenic changes (17% versus 9%, p < 0.04) and type II fiber atrophy (22% versus 6%, p < 0.0005) were more common in the elderly, whereas normal findings tended to be less frequent (19% versus 35%). In at least 68% of patients in both groups with the histologic diagnosis of myopathy, either the CK was elevated or the EMG was consistent with that diagnosis. Our study indicates that (1) the spectrum of histopathologic changes in the two groups differs because of a higher frequency of neurogenic change and type II atrophy in the elderly, and (2) the accuracy of clinical diagnosis of myopathy in the elderly approximates that in a younger population. PMID- 8469345 TI - The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. AB - The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%, and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently--6% of IDDM and 1% of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469347 TI - Prognostic significance of the onset mode in parkinsonism. AB - Early recognition of the prognosis in parkinsonism is important for both the management and studies aimed at preventing progression of disease. Less favorable prognosis is reported in early-onset postural instability and gait difficulty (PIGD) than in the tremor-onset cases, but the reasons for this are unknown. In 70 autopsy-verified cases, 11 (15.7%) had PIGD, and 34 (49%) had tremor onset. Improvement on levodopa was more common in the tremor-than the PIGD-onset cases (p < 0.05). The majority of tremor-onset cases had Lewy body disease, while the majority of PIGD-onset cases had other forms of pathology. Survival was shorter in the PIGD- than the tremor-onset cases (p < 0.05). PMID- 8469348 TI - Long-term safety of azathioprine therapy in multiple sclerosis. AB - We compared the frequency of malignancies in 207 multiple sclerosis patients (mean age 35.75 years, SD 10.60) who took 2.0 mg/kg azathioprine daily (mean duration 4.16 years; SD 2.38) and in 247 nontreated patients (mean age 35.44 years; SD 11.94). Five malignancies were diagnosed in the azathioprine group compared with seven in the control group. The age-adjusted occurrence rate was 3.62/1,000 person-years (95% CI, 1.17 to 8.43) in the treated and 4.24/1,000 person-years (95% CI, 1.70 to 8.73) in the nontreated group; the age-adjusted relative risk of developing a tumor was 0.85. PMID- 8469349 TI - Longitudinal experience with botulinum toxin injections for treatment of blepharospasm and cervical dystonia. AB - We performed a longitudinal analysis of the effects of repeat botulinum toxin (BTX) injections in 42 patients with blepharospasm (BL) and 115 patients with cervical dystonia (CD) who received BTX injections between 1984 and 1992 in at least five separate treatment sessions. Although the BL patients were significantly older (59.8 years) than the CD patients (50.6 years; p < 0.001), there were no other demographic differences between the two groups. While the total dose per treatment session and the peak effect rating remained the same, the duration of benefit increased and the number of complications decreased during the course of treatment. We concluded that chronic treatment with BTX in patients with BL and CD is not associated with any decline in benefit, and that efficacy may improve slightly with repeat treatments. PMID- 8469350 TI - Contrast agent overdose causing brain retention of contrast, seizures and parkinsonism. AB - A patient received an overdose of intravascular contrast medium and experienced protracted seizures associated with radiographic evidence of prolonged retention of the contrast agent in the cerebral cortex, basal ganglia, and thalami. This is only the second report and the first survivor of a similar neurologic syndrome occurring in a patient after contrast agent overdose. After the seizures resolved, there was a transient period of parkinsonism probably due to the toxic effect of contrast on the basal ganglia. PMID- 8469351 TI - Broad A bands of striated muscle in Leber's congenital amaurosis: a new congenital myopathy? AB - A 2-year-old boy with Leber's congenital amaurosis, hypotonia, depressed myotatic reflexes, and delayed motor development had numerous foci of broadened or smeared A bands, loss of distinct I bands, and near-normal Z lines in biopsied muscle. The thick filaments in these lesions appeared misaligned, suggesting an abnormality of the M line or of the structural protein connectin. This unique alteration represents the first described morphologic abnormality of muscle in a patient with Leber's congenital amaurosis. PMID- 8469352 TI - Guillain-Barre syndrome (GBS) with bilateral optic neuritis and central white matter disease. AB - A patient with acute Guillain-Barre syndrome (GBS), recovering following plasmapheresis, developed bilateral optic neuritis with extensive CNS white matter lesions on MRI. This illness was associated with Mycoplasma pneumoniae infection. The rare association of GBS with CNS disease raises a possibility of a shared pathogenic CNS and PNS epitope in these cases. PMID- 8469353 TI - Fulminant rhabdomyolysis in a patient with dermatomyositis. PMID- 8469354 TI - Dropped head syndrome. PMID- 8469355 TI - Dropped head syndrome. PMID- 8469357 TI - Secondary syringomyelia. PMID- 8469356 TI - ECT-induced status. PMID- 8469358 TI - [Evaluation of the endometrium by vaginal ultrasonography]. AB - A group of 131 women aged between 35 and 70 years old were examined using endo vaginal ultrasonography. Of the patients examined, 45 had been in menopause for at least 2 years and 86 were pre-menopause. 48.9% of the post-menopause patients reported loss of blood and 69.8% of pre-menopause patients reported alterations in the menstrual cycle. Ultrasonography was performed using an endo-vaginal 5 MHz (Ansaldo 600) probe with the patient in a dorsosacral position. During the course of ultrasonography the appearance of the endometrium, in particular its thickness, dyshomogeneity and, in pre-menopause women, its correspondence with the stage of the ovarian cycle, were examined. Taking these parameters into account, the type of endometrial echo patterns were classified, separating the cases into pre- and post-menopause groups. Of the women in menopause, 22 underwent curettage due to symptoms, independently of endometrial thickness which was over 4 mm in 50% of cases, 3 women underwent curettage following ultrasonographic indications, whereas the remaining 20 underwent hysterectomy due to other pathologies. Of the pre-menopausal group, 10 underwent curettage following ultrasonographic indications and 42 due to symptoms; the remaining patients underwent hysterectomy due to pathologies not related to the endometrium. A clearly defined role of endovaginal ultrasonography in the diagnosis of endometrial pathologies emerges if ultrasonographic findings are correlated with histological ones. In the group of post-menopausal women (45), all those cases which were histologically classified as endometrial carcinoma (4) were associated with an endometrial thickness over or equal to 4 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469359 TI - [Endometrial adenocarcinoma during the fertile age]. AB - Adenocarcinoma of the endometrium in patients 45 years old or younger accounts for 3-8% of all endometrial cancers diagnosed. Ten women of age = 45 years treated for endometrial cancer stage I in our Clinic of Obstetrics and Gynaecology from December 1979 to December 1988. Two cases were nulliparae, none of the 10 patients had Polycystic ovary syndrome and only was obese. In 80% of these cases the presenting symptom was abnormal vaginal bleeding and one patient had coexisting ovarian neoplasia (endometrioid carcinoma). Atypical endometrial hyperplasia was diagnosed in only one case. None of the patients had metastases or capillary like spaces invasion. Our policy was to treat these patients by hysterectomy (Piver 1 or 2), bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy. One patient received adjuvant postoperative radiation therapy (49.5 Gy). One women was submitted two years later to radical mastectomy for ductal carcinoma of the breast. Endometrial adenocarcinoma in premenopausal women is generally of favourable histotype, at early stage and low grade, with excellent prognosis. The problem of quality of life is therefore of utmost importance. After surgical castration 4 of our patients experienced discomfort and excessive weight gain. The implications of long-term estrogen deprivation in younger patients must be seriously considered against as the change of ovarian conservation of hormonal replacement therapy. PMID- 8469360 TI - [Splenectomy in cytoreductive surgery in ovarian cancer]. AB - During the course of surgery for the treatment of ovarian cancer, splenectomy is rarely performed since this tumour rarely infiltrates the parenchyma although it spreads around the spleen. Surgery is significant if surgical efforts successfully reduce tumour volume to less than one centimetre in diameter. Perisplenic involvement is frequent, even if not always massive and infiltrating, in relation both to biological aggressiveness and clinical and instrumental diagnostic delay. Between January '81 and December '91 a total of 16 splenectomies were performed during the course of surgery relating to 311 (5.1%) patients suffering from mullerian ovarian carcinoma at the 3rd and 4th stage. Of these, 7 were performed during the first operation and 9 during the course of a second-look. The mean age of patients was 56 with a range of 33-71 years. Massive hilar infiltration was found in 14 cases, in 7 together with contemporary capsular infiltration. Parenchymal infiltration was present in 3 cases; one splenectomy was performed following an iatrogenic complication during the mobilization of the left colic flexure, necessary for the creation of the colon rectal anastomosis. Splenectomy was always well tolerated in an overall assessment of surgery and was without severe local complications. The most frequent complications were pleural (7/16) with reactive effusion and bronchopulmonary with basal dystelectasia (3 cases) and bronchopneumonic foci (4 cases). A silent hematoma in a splenic site was revealed using ultrasonography in 3 cases but resolved spontaneously without requiring drainage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469361 TI - [Epidemiologic study of cervico-vaginal pathology in IUD users]. AB - 1800 intrauterine contraceptive device users, during a period of more than thirteen years, and 1800 control non-users were examined clinically, cytologically and histopathologically for cervical pathological lesions. There was an increase, but not statistically significant, in the incidence of metaplasia, dyskariosis or mild dysplasia. There was no difference in neoplastic lesions. PMID- 8469362 TI - [Screening for ovarian carcinoma]. AB - Approximately 1 in 70 women in the USA will develop ovarian cancer in their lifetime. As the incidence of ovarian cancer is higher than that of cervical cancer, an effective screening program is indicated from a medical point of view. This article examines the reduction in ovarian cancer mortality that might be achieved if we can develop a screening test for the detection of this disease during its preclinical phase. Until recently the only potential screening test for ovarian cancer was vaginal examination. With pelvic examination small ovarian lesions are often missed. Ultrasound examination of the ovaries is a much more reliable method for examining the ovary than gynecologic palpation. The combination of serum CA125 measurement with ultrasound examination offers the most specific and sensitive method for the early detection of ovarian cancer. Question concerning the optimal population to screen remain unanswered. If a screening protocol for ovarian cancer is available, demonstration that it results in a reduction in mortality in the screened population will be required. This will only be obtained by performing a large population based, randomised controlled study. Therefore, a simple and reliable screening test for the early detection of ovarian cancer is still urgently required. PMID- 8469363 TI - [Pregnancy in HIV positive women: psycho-emotional aspects. Study of 16 cases]. AB - The aim of this study was to analyse the day-to-day life of HIV-positive women during pregnancy and to assess the emotions deriving from their relations with the baby during the first few months of life. The study was carried out on a group of 16 HIV-positive women aged between 19 and 37 years old (mean age 27.3 years) who underwent a guided interview using a questionnaire. The questionnaire, which was mainly based on questions requiring a free answer, focused on four main areas: 1) the woman's reaction to HIV-positive status; 2) the influence of HIV positive status on relations with her partner and surroundings; 3) the interaction between pregnancy and the HIV-positive status; 4) the relation between mother and children after birth and during the first few months of life. 56.25% of the women interviewed had become infected by intravenous drug injection, 25% through heterosexual relationships and 12.5% through blood transfusions. The cause was unspecified in 6.25%. The women had been aware of their HIV-positive status for between one and four years. Their reactions to HIV positive status were predominantly denial, condemnation, and depression accompanied by a sense of death, anxiety and of being different. Relations between couples were influenced in a variety of ways by the new situation: 4 women reported a diminished frequency of sexual relations, one women reported reduced libido, 10 women did not notice changes in sexual relations and one woman did not reply.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469364 TI - [Erythrocyte zinc-protoporphyrin content in pregnancy]. AB - The assessment of iron deficiency represents a major aspect of routine laboratory chemico-clinical analysis, but the results provided by traditional hemato clinical tests (sideremia, transferrinemia, mean cell volume and red blood cell levels) may not prove conclusive. During pregnancy iron deficiency is common and it would be extremely valuable to obtain a precise method of evaluating anemia. The assay of erythrocytic zincoprotoporphyrin (ZNPP) offers further diagnostic possibilities. This study aimed to evaluate the behaviour of ZNPP and other common laboratory indices in pregnant and non-pregnant women in order to assess the value of assaying ZNPP levels. Some common parameters for the study of sideropenic anemia were determined using the methods employed in our laboratory: mean cell volume (MCV), hemoglobin (Hb), sideremia (Fe), ferrinemia and ZNPP in women of child-bearing age. The tests were prescribed for preventive tests prior to the administration of oral contraceptives and/or in pregnant women undergoing control tests. No tests were made to ascertain professional or environmental exposure to lead or its derivatives. Precision was evaluated by calculating the coefficient of variation (CV) for repeated tests. If a detailed analysis is made of the behaviour of some parameters during pregnancy it can be seen that there is a progressive diminution of sideremia and ferritin, accompanied by increased levels of ZNPP. The potentially most characteristic parameters are ferritin and ZNPP which do not have a Gaussian distribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469365 TI - [Circumference of the fetal stomach. Echographic study in 100 normal pregnancies]. AB - Fetal stomach circumference were measured sonographically in 100 fetuses with gestational ages ranging from 16 to 40 weeks. Normograms of the mean +/- 2SD for circumference of the fetal stomach were generated throughout pregnancy. A high degree of correlation was observed between gestational age and stomach circumference (r = 0.963). These data provide a method by which variations from the norm can be assessed, and offer potential prenatal diagnosis of a variety of gastrointestinal lesions. PMID- 8469366 TI - [Continuous subcutaneous administration of terbutaline in the therapy of threatening premature labour]. AB - The purpose of this study was to evaluate the tocolytic efficacy of terbutaline, administered subcutaneously in a low-dose continuous infusion, and intermittent high-dose boluses. The population study consisted of 13 women admitted with the diagnosis of Threatened Preterm Labour. Before starting chronic infusion by terbutaline, patients received 48 hour of therapy with intravenous MgSO4 for acute tocolysis. Therapy with microinfusor was continued until the 37th week of gestation or until labor. The mean gestational age at the beginning of therapy was 25.6 +/- 3.5 and pregnancies were prolonged an average of 65.5 +/- 29 days. In any case uterine activity was diminished by terbutaline therapy in all patients. Patient tolerance was excellent and there were no significant complications due to the therapy. PMID- 8469367 TI - [Decapeptyl 3.57mg in the therapy of the fibromatous uterus. Authors' contribution]. AB - Thirty women in their reproductive age who were diagnosed for leiomyomata uteri were treated for 6 months with Triptorelin slow release, 3.75 mg, every 28 days, i.m. The results obtained were highly satisfactory and were confirmed by ultrasound scanning and clinical examination. The drug was extremely well tolerated by patients and the side-effects reported never required the interruption of treatment. PMID- 8469368 TI - [Intraepithelial cervical lesions: colpo-microcolposcopic diagnosis]. AB - Integration of colposcopy and microcolposcopy allows to perform a complete study of eso- endo-cervix, for a diagnostic and topographic evaluation of cervical intraepithelial lesion. We have endoscopically studied 172 patients with histologically demonstrated CIN. In 218 cases (74.4%) the microcolposcopical evaluation corresponded to the histological diagnosis. These data confirm the methodological effectiveness of microcolposcopy and recommend it as helpful mean for cervical pathology investigation. However we believe that histological evaluation is necessary for a correct staging of the lesion. According to our experience indications for microcolposcopy are: 1) identification of endocervical lesion and squamo-columnar junction, when colposcopically not evident; 2) possibility of performing a "tailored" conization; 3) study of endocervix after conization. PMID- 8469369 TI - Growth factor modulation of surface ganglioside expression in cloned neoplastic glia. AB - Cloned neoplastic astrocytes from a human glioma-derived cell line (IPSB-18) were grown in fetal calf serum (FCS)-supplemented culture medium in the presence of three growth factors. Basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF) induced an increase in the number of cells positive for the ganglioside-recognizing monoclonal antibody, A2B5. No such growth factor-mediated induction could be detected in cells maintained in plasma-derived serum (PDS)-supplemented medium. Small molecules, removed from PDS during dialysis, may, therefore, act synergistically with growth factors in the control of ganglioside synthesis. PMID- 8469370 TI - Corticotropin-releasing factor suppresses the afterhyperpolarization in cerebellar Purkinje neurons. AB - Corticotropin-releasing factor (CRF) is present in climbing fibers and their terminations on Purkinje neurons. To determine whether CRF may have a postsynaptic action in this pathway, CRF effects on the electrophysiological properties of cultured cerebellar Purkinje neurons were studied. CRF produced a dose-dependent reduction of the amplitude of the afterhyperpolarization (AHP) which follows a current-induced spike train. The effect of CRF on the AHP was specific in that CRF did not significantly alter input resistance, membrane potential, amplitude of the depolarizing-off response produced at the termination of a hyperpolarizing current pulse, or the number of depolarization-induced simple spikes. Suppression of the AHP by CRF may be one mechanism by which CRF regulates the response of Purkinje neurons to other transmitters in the climbing fiber pathway or in other inputs to Purkinje neurons. PMID- 8469372 TI - Nicotinic acetylcholine receptor in dissociated rat nucleus tractus solitarii neurons. AB - The ACh-activated response of the acutely dissociated neuron from the rat nucleus tractus solitarii (NTS) was investigated using conventional and perforated-patch techniques. In the present preparation, ACh and nicotine evoked inward transient currents in approximately 30% of NTS neurons tested. The ACh-activated inward current reversed the direction near 0 mV and was inhibited by D-tubocurarine in a dose-dependent manner. In contrast, muscarine resulted in no detectable changes in the NTS neurons. Some populations of the NTS had nicotinic but no muscarinic acetylcholine receptors. PMID- 8469371 TI - Glycine sensor in the hepato-portal system and their reflex effects on pancreatic efferents in the rat. AB - We earlier reported the existence of vagal arginine, alanine, and leucine sensors in the liver which modulate amino acid-induced pancreatic hormone secretion. To determine the possible existence of glycine sensors in the liver and their reflex effects, afferent discharges from the hepatic branch and efferent discharges from the pancreatic branch of the vagus nerve were recorded. Intraportal administration of 0.1, 1, and 10 mM of L-glycine solution (0.1 ml) depressed the afferent discharge rate of the hepatic branch of the nerve in a dose-dependent manner, and increased the efferent discharge rate of the pancreatic vagal branch. The results suggest the existence of glycine sensors in the hepato-portal system that exert reflex regulation on the pancreatic vagus nerve activity. PMID- 8469373 TI - Neuropeptide Y stimulates DNA synthesis in vascular smooth muscle cells. AB - Neuropeptide Y (NPY) stimulated DNA synthesis in porcine aortic smooth muscle cells in a concentration-dependent manner. [Leu31, Pro34]NPY, a Y1-specific agonist, was several hundred times more potent than NPY(13-36), which preferentially bound to Y2 receptors, for stimulating DNA synthesis. On the other hand, human pancreatic polypeptide had no effect. The potency of NPY and related peptides for stimulating DNA synthesis paralleled their potency for increasing the cytosolic free Ca2+ concentration in the cells. Pertussis toxin treatment completely blocked both effects of the peptides. Thus, NPY may induce Ca2+ mobilization and stimulation of DNA synthesis in vascular smooth muscle cells via Y1 receptors whose signal transduction system involves pertussis toxin-sensitive GTP-binding protein(s). PMID- 8469374 TI - Region specific expression of furin mRNA in the rat brain. AB - The distribution of furin mRNA was examined in the rat central nervous system. Northern blot analysis reveals the presence of a 4.4 kb band in all brain tissues examined. In situ hybridization analysis of frozen rat brain sections using a radioactively labeled antisense cRNA probe to rat furin demonstrated moderate to low levels of expression in both neuronal and non-neuronal tissue in all areas examined. Interestingly, higher levels of furin were expressed in selective regions which include the ventricles (the choroid plexus and ependymal cells), the islands of Calleja, the hippocampus and the pineal gland. the ubiquitous localization of furin in the brain is consistent with its postulated role as a vital convertase important in the processing of proproteins negotiating the constitutive pathway of secretion. However, the higher expression of furin mRNA in distinct brain areas suggests a more active role in the processing of proproteins synthesized in these tissues. PMID- 8469375 TI - Failure of 2'-deoxycoformycin to protect against transient forebrain ischemia in rat. AB - We determined whether 2'-deoxycoformycin (DCF), a potent highly specific inhibitor of adenosine deaminase (ADA), protected against transient forebrain ischemic neuronal injury in rat. Anesthetized male Sprague-Dawley rats received i.p. injections of either saline, 0.5 mg/kg or 5 mg/kg DCF 2 h before undergoing a 10-min forebrain ischemic insult induced by bilateral carotid artery occlusion with concomitant hypotension. Rat brain sections taken 7 days post-ischemia showed damage mostly in the CA1 region of the hippocampus. Quantification of neuronal injury showed no significant differences between saline- or DCF-treated rats. These results indicate that, contrary to previous reports, DCF does not protect against the neuronal damage that follows forebrain ischemia in rat. PMID- 8469376 TI - Basket-like interneurones in layer II of the entorhinal cortex exhibit a powerful NMDA-mediated synaptic excitation. AB - Spiny stellate neurones of layer II of the entorhinal cortex (EC) provide the perforant path input to the dentate gyrus. Previous studies have shown that synaptic responses of these neurones are dominated by GABAergic inhibition. The present study describes intracellular recordings from 'fast-spiking' interneurones in layer II which may be the basis of the synaptic inhibition. Lucifer yellow fills of fast-spiking cells revealed neurones with a widespread axonal arborization forming basket-like complexes around unlabelled cells in layer II. Synaptic activation of the fast-spiking cells evoked long duration excitations which were mediated largely by NMDA receptors. A fast AMPA/kainate EPSP was also detectable. These neurones have morphological and physiological properties which make them well-suited to exert a widespread inhibitory control over the efferent output of layer II to the dentate gyrus. PMID- 8469377 TI - Role of nitric oxide in the coupling of cerebral blood flow to neuronal activation in rats. AB - We tested the hypothesis that nitric oxide (NO) is a mediator in the coupling of cerebral blood flow to neuronal activation. The production of NO was blocked in anesthetized rats with the NO-synthase inhibitor N omega-nitro-L-arginine (L-NA). In controls, vibrissae stimulation for 60 s led to a fast (< or = 2 s), 17% increase in regional cerebral blood flow (rCBF) in the contralateral somatosensory cortex. Systemical (10 mg/kg) as well as topical (10(-3) M) application of L-NA reduced the response to stimulation by approximately 50%. Systemical application primarily attenuated the early component of the response, whereas topical application led to an attenuation throughout the whole 60-s stimulation interval. We conclude that NO is involved in rCBF coupling to neuronal activation. PMID- 8469378 TI - Nerve growth factor and its receptor are differentially modified by chronic naltrexone treatment during rat brain development. AB - In order to examine the relationship between the action of opioid neurotransmitters and growth factors in the regulation of brain development, we have studied the long-term effect of the opiate antagonist naltrexone (NTX) on the content of nerve growth factor (NGF) in cortex, hippocampus, septum and neostriatum, and on NGF receptor (NGFRs) levels in cortical membranes. 50 mg/kg NTX treatment induced a decrease in the number of 125I-NGF high-affinity binding sites, without detectable changes in NGF levels. However, low doses of NTX (1 mg/kg) produced no differences in 125I-NGF binding sites, but induced a decrease in NGF levels in hippocampus, septum and neostriatum. These results suggest that NGF and NGFRs could be involved in the trophic effects of opioids during brain development. PMID- 8469379 TI - Inward potassium rectifier current in type I vestibular hair cells isolated from guinea pig. AB - Large inward current activated by hyperpolarization was studied using whole cell patch clamp technique in type I vestibular hair cells of guinea pig. Near the resting membrane potential, at an holding potential of -60 mV (HP -60), this current increased with hyperpolarizing steps and showed time-dependent decay for steps below -80 mV. This current was progressively inactivated at more negative holding potential and was totally abolished at HP -90 mV. The underlying conductance was a K+ conductance as indicated by: (i) its dependence on the external potassium concentration; (ii) its tail currents, which reversed at about -90 mV in solutions with a normal gradient for K+ ions. Pharmacological studies revealed that external application of 4-aminopyridine (5 mM) reversibly blocked (95%) the total inward current, while external application of tetraethylammonium (10 mM) or cesium (2 mM) did not significantly affect the amplitude of this current. This potassium inward rectifier current could contribute to restoration of the resting membrane potential during negative stimulations. PMID- 8469380 TI - Reduction in pineal N-acetyltransferase activity and pineal and serum melatonin levels in rats after their exposure to red light at night. AB - Pineal gland N-acetyltransferase (NAT) activity and pineal and serum levels of melatonin declined linearly in albino rats exposed to different irradiances (low, 170 microW/cm2; moderate, 420 microW/cm2; high, 1040 microW/cm2) red light during the middle of the night. High intensity red light (1040 microW/cm2) was as effective as white light (670 microW/cm2) in suppressing pineal NAT activity and pineal and serum melatonin levels. The lowered melatonin levels and the reduction in NAT activity following exposure to red light suggest that red light cannot be regarded as 'safe' light when studying circadian melatonin production in the albino rat, at least at the intensities used in this experiment. PMID- 8469381 TI - Anatomy of the turtle cerebellorubral circuit studied in vitro using neurobiotin and biocytin. AB - We have combined the rapid anterograde and retrograde transport of neurobiotin and biocytin with the extended viability of the isolated turtle brainstem cerebellum to conduct in vitro studies of the chelonian cerebellorubral circuit. Tracers were pressure injected in 15-25 nl quantities and the optimal transport time was 16 h. Tissue sections were incubated with avidin-biotin-HRP complex and reacted with DAB. Retrogradely labeled soma, dendrites and axons, and anterogradely labeled axons and to a lesser extent terminals were visible with both tracers. Red nucleus injections resulted in dense retrograde label in the contralateral lateral cerebellar nucleus and a heavily labeled contralateral rubrospinal tract. Cerebellar nucleus injections revealed light retrograde and dense terminal label in the contralateral red nucleus, together with retrograde label in a cell cluster in the ipsilateral ventrolateral medullary reticular formation, an area we identify as the lateral reticular nucleus. Injections into this medullary region resulted in heavy mossy fiber input to the ipsilateral cerebellum and moderate retrograde label in the contralateral red nucleus. These results identify prominent recurrent projections between the lateral cerebellar nucleus, red nucleus and lateral reticular nucleus, in addition to revealing other features of the cerebellorubral circuit. PMID- 8469382 TI - Reduced membrane-associated protein kinase C(beta) immunoreactivity in the hippocampus of reserpinized rat brain. AB - Protein kinase C(beta) immunoreactivity was determined in the membrane and cytosol fractions of the hippocampus, frontal cortex and cerebellum after repetitive, intraperitoneal administration of reserpine. A marked decrease in the immunoreactivity was observed in the membrane of the hippocampus, while no significant change was found in any other subfractions of the frontal cortex or cerebellum. These findings suggest a novel mechanism regulating the distribution of protein kinase C. The topographical selectivity in the present study may indicate the importance of the alteration of protein kinase C in the pathophysiological mechanism in Alzheimer's disease. PMID- 8469383 TI - Increases in brain polyamine concentrations in chemical kindling and single convulsion induced by pentylenetetrazol in rats. AB - Concentrations of the polyamines, putrescine, spermidine and spermine were investigated in rat brains, in which chemical kindling or single convulsion had been induced by intraperitoneal injection of pentylenetetrazol (PTZ). A single injection of 60 mg/kg of PTZ produced tonic-clonic convulsion and increased the putrescine concentration 8 h after the injection. At lower doses of PTZ (10 and 30 mg/kg), neither marked behavioral seizure nor significant change in any polyamine concentration was observed. On the other hand, repeated injections of 30 mg/kg of PTZ eventually resulted in intense motor seizures (PTZ kindling) and increased the concentrations of all three polyamines. The most marked increase was detected in putrescine 1-48 h after the intense seizures. The increase in putrescine was clearly higher in PTZ kindling than in single convulsion. These results suggest that increases in polyamine concentrations are involved in neuronal excitability in the epileptic brain. PMID- 8469384 TI - Circulating immune complexes in sera from patients with Alzheimer's disease, multi-infarct dementia and Down's syndrome. AB - Recent data suggest that immunological mechanisms may be implicated in the pathogenesis of Alzheimer's disease (AD). We tested the presence of circulating immune complexes (CIC) in the sera from dementia and Down's syndrome (DS) patients and age-matched controls using two methods: Clq-binding Elisa (ClqB Elisa) and conglutinin-binding Elisa (KgB-Elisa). The probable AD and multi infarct dementia (MID) patients had more frequently CIC in their sera as compared to elderly non-demented subjects (Chi-square; P < 0.05). The highest frequency of positive findings was detected for 10 DS patients (8 KgB-Elisa and 7 ClqB-Elisa positive) whereas only 1 of 10 young controls showed ClqB-positivity. In the AD patients the cognitive decline as assessed by the Mini-Mental Status test correlated significantly with CIC values. The study supports the view that systemic autoimmune mechanisms may be involved, at least partly, in dementing processes. PMID- 8469385 TI - Tight junction complexity in the retinal pigment epithelium of the chicken during development. AB - In the avascular retina of birds, the pigment epithelium (RPE) is the main site of the blood-retina barrier. Tight junctions (TJs) connect the pigment epithelial cells and represent the structural substrate of the barrier function. We investigated, by means of the quantitative freeze-fracturing technique, the TJs of the chicken RPE during development and compared them with the TJs of choroid capillary endothelial cells which are known to be fenestrated. The association of TJs with the protoplasmic membrane leaflet (P-face) is more pronounced in the RPE than in the choroid vessels. Between embryonic day 15 (E15) and E19, we observed a significant increase in the TJ complexity in the RPE, but not in the choroid vessels. The increase coincides with the morphological and functional maturation of the chicken retina suggesting that complex P-face-associated TJs in the RPE are necessary for the formation of an effective blood-retina barrier. PMID- 8469386 TI - Three openings of the blood-brain barrier produced by forebrain ischemia in the rat. AB - A sensitive radiotracer method was used to explore the time course and regional pattern of blood-brain barrier (BBB) opening that occurs in a rat forebrain ischemia model that mimics temporary cardiac arrest. Immediately following 10 min of ischemia, transfer constants (Ki) for blood to brain permeation of [3H]sucrose were augmented severalfold, indicating widespread BBB opening. After 6 h, a delayed intensification of opening was evident in striatum and hippocampus, regions known to undergo selective, delayed neuronal death. There was generalized BBB recovery by 24 h except in experiments that involved prolonged ischemia (25 min) or concomitant brain hyperthermia (41 degrees C, 10 min). These protocols evoked a third opening; a marked upward increment in Ki and % H2O developed in neocortex between 6 and 24 h post-ischemia. Pharmacological or other manipulations of these temporal and regional patterns of altered transfer constants may aid understanding of the interplay between microvascular damage, edema, and neuronal death following brain ischemia. PMID- 8469387 TI - Extension of optic nerve fibers on genetically modified cells producing brain derived neurotrophic factor. AB - Since brain-derived neurotrophic factor (BDNF) promotes the survival of retinal ganglion cells (RGCs), we transfected a rat BDNF cDNA into rat fibroblasts, and retinal fragments of rat embryos were cultured on cell monolayers of these cells. Retinal fragments showed enhanced neurite extension on BDNF-transfected cells compared with that on control cells. The degree of the neurite extension, however, decreased depending upon the embryonic stages. These results suggest that fibroblasts genetically modified to produce BDNF might be a promoter of neurite extension by RGCs, but this does not apply to the RGCs of late embryonic stages. PMID- 8469388 TI - Does frontal-plane asymmetry in compensatory postural responses represent preparation for stepping? AB - The bilateral symmetry of feet-in-place responses to postural perturbations in the anterior-posterior direction has not been well studied. This paper presents evidence that right- and left-leg responses that appear to be approximately symmetrical in the sagittal plane may actually involve an asymmetry in the frontal plane, namely, a lateral weight shift. Comparison with trials where subjects stepped suggests that these lateral weight shifts represent early preparations for stepping responses that are aborted before the foot is actually lifted. Thus, it would seem that compensatory stepping involves a sequence of discrete modifiable stages, rather than a single immutable motor program. Moreover, postural responses that appear to be similar in the sagittal plane may actually be seen to involve quite different postural strategies, i.e. in terms of preparation for stepping, when viewed in the frontal plane. PMID- 8469389 TI - Regional differences in the ontogeny of 5-hydroxytryptamine-1C binding sites in rat brain and spinal cord. AB - Developmental profiles of [3H]mesulergine-labelled central 5-HT1c binding sites differed regionally in the rat during the first 5 weeks postnatal. At birth, cortical 5-HT1c sites were 24-32% of adult levels and increased significantly by 14-21 days. In brainstem, the majority of 5-HT1c sites were already present at birth and increased further by 10 days, which was earlier than in other regions. A pattern of increasing binding site density was also found in hippocampus, diencephalon, and spinal cord. Cerebellar 5-HT1c sites remained at low levels throughout. A mature pattern of regional differences was apparent by 21-28 days with a new rank order: cortex, diencephalon > spinal cord, brainstem, hippocampus > cerebellum. These trends were seen whether Bmax was expressed according to brain weight or protein concentration. The regional contrast in the ontogeny of 5 HT1c binding sites may be relevant to the proposed role of 5-HT as a growth factor in brain development. PMID- 8469390 TI - L-arginine and nicotinamide adenine dinucleotide phosphate alter dark voltage and accelerate light response recovery in isolated retinal rods of the frog (Rana temporaria). AB - Effects of intracellularly applied L-arginine and nicotinamide adenine dinucleotide phosphate (NADPH) on the dark voltage and light responses of retinal rods were studied by means of the whole-cell patch-clamp technique. In this mode an exchange of substances by diffusion between cytosol and pipette medium occurs (Pflugers Arch., 411 (1988) 204-211). In retinal rods a loss of nucleotides is reflected by a hyperpolarization of the dark voltage and by a prolongation of the light responses (Vis. Neurosci., 2 (1989) 101-108). Intracellular application of L-arginine prevented the prolongation of the light responses and NADPH accelerated the light response recovery and in addition depolarized the photoreceptor cells. The effects were similar to those observed before upon application of the nitric oxide (NO)-releasing substance sodium nitroprusside (Vis. Neurosci., 9 (1992) 205-209). It is therefore assumed that the observed effects are linked to the NO-synthase and to an activation of a guanylate cyclase by NO. It is concluded that the level of NADPH in photoreceptor cells may affect the metabolic flux of guanosine 3',5'-cyclic monophosphate (cGMP). PMID- 8469391 TI - Mechanisms underlying post-inspiratory depolarization in post-inspiratory neurons of the cat. AB - The mechanism of the post-inspiratory depolarization in bulbar post-inspiratory neurons was investigated in decerebrate cats with a coaxial multibarrelled microelectrode technique. Iontophoresed tetrodotoxin eliminated a dominant part of the post-inspiratory depolarization and left a small depolarization to occur. This residual potential was increased with depolarization. When depolarization exceeded a potential of average -63 mV, there appeared a large bell-shaped depolarization that was suppressed by iontophoresed cadmium. These results suggest that the post-inspiratory depolarization in this neuron is formed by the cooperation between excitatory synaptic potentials and voltage-dependent Ca2+ currents. PMID- 8469392 TI - Ultrastructural changes in the presynaptic region of outer hair cells after acoustic stimulation. AB - Protection against noise trauma results by sound-conditioning animals to a low level, long-term acoustic stimulus prior to a damaging exposure. It is known that the outer hair cells are selectively protected by sound-conditioning. The aim of the present study was to determine if the intrinsic properties of the outer hair cell had been modified by sound-conditioning. A stimulus-related increase in the vesicle content in the presynaptic region was found. It is suggested that the outer hair cells are involved in sound conditioning and that changes in the presynaptic region can be one correlate to the protection against noise trauma by sound-conditioning. PMID- 8469393 TI - Altered distribution of synaptic densities at aberrant synapses in the chick cochlear nucleus. AB - The role of axon-target cell interactions in shaping the prevalence and distribution of synaptic densities was studied in an experimentally-induced aberrant functional projection from the chick cochlear nucleus (nuc. magnocellularis, NM) to the contralateral NM. Contact with an abnormal target appears to induce in the aberrant axons a pattern of presynaptic densities resembling that in normal cochlear nerve endings in NM. NM axon terminals induced similar numbers of postsynaptic densities (PSDs) per unit length of membrane apposition in both their normal and abnormal targets but the longer membrane apposition in the highly invaginated aberrant terminal in NM results in a significantly greater amount of postsynaptic density per ending. These auditory neurons thus appear able to adjust a variety of features to permit assembly and maintenance of a novel functional synapse. PMID- 8469394 TI - Muscarinic receptor-mediated induction of Fos protein in rat brain. AB - Recent studies have shown that the centrally active muscarinic agonist pilocarpine induces c-fos mRNA in rat cortex. Here we describe the localization of muscarinic receptor-induced FOS protein, within the rat central nervous system (CNS), following administration of pilocarpine (25 mg/kg). High levels of FOS induction were apparent in many forebrain structures including the primary olfactory (piriform) cortex, nucleus accumbens, amygdala, hippocampus, neocortex and supra-optic nucleus of the hypothalamus. Within the neocortex FOS induction followed a laminar distribution being highest in layers 4 and 6 with lower induction seen in layers 2 and 5. Other areas showing FOS induction included the striatum, septum, inferior colliculus, thalamus, hypothalamus and several brainstem nuclei. Both atropine (10 mg/kg) and pirenzepine (100 mg/kg) reduced FOS induction suggesting that a pirenzepine-sensitive muscarinic receptor was involved. The possible significance of muscarinic-mediated FOS induction, to cholinergic kindling and the cholinergic hypothesis of learning and memory, is discussed. PMID- 8469395 TI - Amphetamine-induced release of diadenosine polyphosphates--Ap4A and Ap5A--from caudate putamen of conscious rat. AB - The release of diadenosine polyphosphates--diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A)--was measured by intracerebral push-pull perfusion in conscious rats after systemic amphetamine injection. Samples were collected from the caudate putamen, and nucleotide compounds were analyzed by HPLC. The presence of Ap4A and Ap5A was demonstrated by their retention times and phosphodiesterase digestion. Dinucleotides were not detectable before amphetamine injection (5 mg/kg). The maximal levels were reached 20 min after the injection with values of 12.9 +/- 0.9 and 11.5 +/- 0.9 pmol/fraction for Ap4A and Ap5A, respectively. A slow and progressive decrease in their concentration followed. This study shows for the first time the amphetamine-induced release of diadenosine polyphosphates in conscious rats, and a role for Ap4A and Ap5A in the central nervous system is therefore suggested. PMID- 8469396 TI - Palmitate transport through the blood-retina and blood-brain barrier of rat visual system during aging. AB - The permeability-surface area product (PA) of [1-14C]palmitate at the blood retina (BRB) and blood-brain barrier (BBB) was determined after short carotid perfusion in male Sprague-Dawley rats at 4, 14 and 28 months of age. For the retina, optic nerve and tract, lateral geniculate body, visual and parietal cortex, there was no significant difference among mean PAs in any age group. For superior colliculus, frontal cortex, striatum, hippocampus and olfactory bulb, a slight but significant increase of PA values was observed between young (4-month old) and senescent (28-month-old) rats. Our results indicate that aging does not affect influx into retina and other structures of rat visual system of the palmitate, a metabolic substrate for which carrier-mediated transport across the BRB and BBB has not been demonstrated. PMID- 8469397 TI - Activation of high-threshold motor units in man by transcranial magnetic stimulation. AB - Motor units (MUs) with low voluntary recruitment thresholds are the first to be activated by transcranial magnetic stimulation. It is not clear, however, if high threshold MUs can also be activated and if they contribute to motor evoked potentials (MEPs). We therefore studied 11 high-threshold motor units in the first dorsal interosseous muscle of 11 healthy subjects. Voluntary recruitment thresholds ranged from 22 to 41% (29.5 +/- 5.6%; mean +/- S.D.) of maximal muscle force. When MUs were driven at their recruitment thresholds, transcranial magnetic stimuli were applied to the vertex. Peri-stimulus time histograms of MU discharges were constructed. All MUs studied revealed a period of increased firing probability at 19-27 ms after the stimulus (primary peak). Stimulus intensities were lower by 10-57% of the maximal stimulator output than required to produce near maximal MEPs in conventional surface EMG recordings in the same subjects. We conclude that high-threshold MUs can be activated by transcranial magnetic stimulation and that they contribute to conventionally recorded MEPs. PMID- 8469398 TI - Both splicing variants of the dopamine D2 receptor mRNA are up-regulated by antipsychotic drugs. AB - We have investigated the effects of antipsychotic drugs on the expression of the two dopamine D2 receptor splicing variants using multiprobe oligonucleotide solution hybridisation. Both long and short mRNA variants were increased in abundance by approximately 2-fold by both haloperidol and loxapine after 32 days drug administration. PMID- 8469399 TI - A novel silent variant at codon 711 and a variant at codon 708 of the APP sequence detected in Spanish Alzheimer and control cases. AB - Pathogenic mutations have been identified in exons 16 and 17 of the beta-amyloid precursor protein (APP) gene in some cases of early onset Alzheimer's disease. Screening of these exons in a number of familial and sporadic cases of Alzheimer's disease in Spain, resulted in the identification of a novel silent variant at codon 711 whose relevance to the AD pathogenesis remains unclear. The 708 variant was also detected in one of normal controls. PMID- 8469400 TI - Coupling of muscarinic receptors to GTP proteins in postmortem human brain- alterations in Alzheimer's disease. AB - The coupling of muscarinic agonist receptors to guanine nucleotide-binding (G) proteins was investigated in the frontal, temporal cortices and thalamus of control and Alzheimer brains by using carbachol in competition experiments with [3H]QNB. In the presence of GppNHp, the carbachol/[3H]QNB competition binding data showed a 6-fold increase in the high-affinity muscarinic agonist coefficient (Ki high) in the thalami of control brains and a significantly increased proportion of low-affinity agonist binding sites (Bmax low) in the temporal cortices of control brains, while no significant effect of GppNHp was observed in Alzheimer brains. The results suggest a disturbance of the muscarinic receptor-G protein coupling in Alzheimer's disease. PMID- 8469401 TI - Evidence that removal of capsaicin accelerates desensitization on the tongue. AB - It has previously been shown that repeated presentations of a moderate concentration of capsaicin could either sensitize or desensitize the tongue, depending upon the temporal pattern of stimulation. Only when stimulation was halted for 5 min or longer did sensitization begin to give way to desensitization. The apparent necessity of a hiatus in stimulation led to the hypothesis that desensitization involved an inability to re-excite quiescent fibers rather than a progressive suppression of stimulated fibers. This hypothesis was tested in the present study by measuring the perceptual response to a non-desensitizing irritant, zingerone, when it was presented at the rate of l/min following a series of capsaicin conditioning stimuli. After an initial, brief period of cross-hyper-sensitization, cross-desensitization developed at a rate equivalent to that observed when no stimulus was presented. Thus, the results disproved the hypothesis that desensitization cannot occur if capsaicin sensitive fibers continue to be stimulated, and suggested that after an initial period of excitation, the removal of capsaicin accelerates the desensitization process. This seeming paradox is discussed in terms of the neural mechanisms that may underlie capsaicin desensitization. PMID- 8469402 TI - MPTP neurotoxicity to cerebellar Purkinje cells in mice. AB - The pyridine derivative 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is recognized as a crucial neurotoxin which destroys nigrostriatal dopamine cells, thereby inducing neurological signs relevant to idiopathic Parkinson's disease. In the present study, we have revealed MPTP neurotoxicity to cerebellar Purkinje cells in mice. Systemic MPTP injections to mice resulted in a substantial loss of Purkinje cells in a dose-dependent fashion. The MPTP-induced Purkinje cell loss occurred markedly in the crus I and II ansiform lobules and the paraflocculus. Such a neurotoxic effect was largely prevented by the monoamine oxidase B inhibitors pargyline and deprenyl, and the dopamine uptake inhibitors mazindol and benztropine. PMID- 8469403 TI - Detection of dynamic changes in cerebral oxygenation coupled to neuronal function during mental work in man. AB - Changes in the oxygenation state of brain hemoglobin during mental work were monitored in real time (time resolution: 1 s) using near-infrared spectrophotometry in 14 healthy volunteers. In a younger group (age range 22-30 years, n = 12), the subjects finding difficulty in solving a problem were accompanied by significant increases in both oxygenated hemoglobin and total hemoglobin, while the subjects making a correct answer without difficulty showed no significant changes in hemoglobin oxygenation. When compared with those younger subjects, observations on the older subject demonstrated a decrease in oxygenated hemoglobin and a reciprocal increase in deoxygenated hemoglobin, unaccompanied by changes in total hemoglobin. PMID- 8469404 TI - MK-801 increases endogenous acetylcholine release in the rat parietal cortex: a study using brain microdialysis. AB - Glutaminergic and cholinergic neuronal interactions were investigated by using the brain microdialysis method in freely-moving rats. Acute administration of (+) 10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801) increased dose-dependently the extracellular acetylcholine (ACh) level in the rat parietal cortex. Significant increases in the extracellular ACh level were observed at doses of 0.4 and 0.5 mg/kg of MK-801, compared with the saline treated group. The increase of extracellular ACh level was eliminated by infusion of 10(-2) M N-methyl-D-aspartate (NMDA). These results suggest that the glutaminergic neuronal system regulates functions of the cholinergic neuronal system. PMID- 8469405 TI - Early postnatal undernutrition impairs protein kinase C-dependent phosphorylation in rat brain synaptosomes. AB - Undernutrition in rat pups was established by restricting feeding time daily. Protein kinase C-dependent phosphorylation in vitro was studied by incubating the mitochondrial-synaptosomal membrane fractions from adult, 18-day-old control and undernourished rats with gamma-[32P]ATP in presence of Ca2+ and phosphatidylserine. In adult and 18-day-old control rats, an increased phosphorylation of three major proteins (49, 53, 84 kDa) were detected in presence of calcium and phosphatidylserine. However, in 18-day-old undernourished rats, calcium/phosphatidylserine activated phosphorylation was found to be significantly impaired with only a slightly increased labelling detected in the 49 kDa protein. PMID- 8469406 TI - Effects of hepatic vagotomy on suppression of water intake induced by hepatic portal infusion of water in water-deprived rats. AB - We investigated the effects of hepatic vagotomy on the suppression of water intake induced by hepatic portal infusion of water by 24-h water-deprived rats. In sham-operated rats, water intake of the portal infusion group was significantly less than that of the jugular infusion group during and after the infusion of deionized water for 3.5 h at a rate of 52 microliters/min. This result reconfirmed our previous findings. On the other hand, in hepatic vagotomized rats, the suppression during the portal infusion of water was not observed, but the suppression after portal infusion was observed. It is concluded that the suppression, at least during the portal infusion of water, was mediated by hepatoportal osmo-receptive (or sodium-receptive) afferent signals contained in the hepatic branch of the vagus nerve. PMID- 8469407 TI - Injections of fluid or septal cell suspension grafts into the dentate gyrus of rats induce granule cell degeneration. AB - This study was originally aimed at investigating the effects of intragyral cell suspension grafts which had been enriched in basic fibroblast growth factor (bFGF) before being implanted into the rat hippocampus denervated by aspiration of the septohippocampal pathways. Whether treated with vehicle alone, vehicle + bFGF, cell suspension with or without bFGF, and irrespective of the surgical treatment (sham-operation, lesions or lesions + grafts), we unexpectedly found approximately 80% of the rats to show morphological alterations in the dentate gyrus (20 weeks post-grafting). These alterations consisted of loss of a part of the granule cells; this loss was most often located in the dorsal leaf of the dentate gyrus. Also, in the close vicinity of the degeneration area, we found severe shrinkage of the molecular layer and disappearance of the typical laminae pattern of acetylcholinesterase distribution. These observations confirm previous findings which showed that fluid injections into the dentate gyrus, a widely used technique for intracerebral administration of drugs, trophic factors or neural grafts, may induce undesirable granule cell necrosis. PMID- 8469408 TI - The time course and location of cerebral evoked activity associated with the processing of colour stimuli in man. AB - Area V4 has been located in man in the region of the fusiform gyrus on the inferior surface of the occipital lobe. Using multiple dipole source analysis on multichannel EEG recordings of visual evoked potentials to coloured 'Mondrian' stimuli in man, we have confirmed that activity is consistently seen in this area regardless of the retinal area stimulated and have obtained new information concerning its time course. Three different localized centres of activity follow the visual stimulus, with peak latencies of 90, 110 and 160 ms, and arising respectively in the region of visual areas V1, V2/V3 and V4. The time course and character of the V4 dipole activity to a colourless black-and-white Mondrian is indistinguishable from that to the coloured Mondrian, supporting the evidence that the cells of V4 are not exclusively concerned with colour processing. PMID- 8469409 TI - Electrical stimulation of the ventroposterolateral thalamic nucleus (VPL) reduces mechanical allodynia in a rat model of neuropathic pain. AB - The effect of electrical stimulation of the ventroposterolateral (VPL) thalamic nucleus on mechanical allodynia in the unrestrained awake rat was investigated. In 7 rats, a monopolar stimulation and recording electrode was implanted in the VPL thalamic representation area of the hindpaw. Exact target localisation was performed by means of thalamic evoked potentials induced by stimulating the contralateral tibial nerve. A peripheral mononeuropathy was induced by partly ligating the right sciatic nerve. Sensitivity of the hindpaws to mechanical stimulation was assessed with a set of von Frey hairs. One to 4 weeks after nerve ligation, all rats showed allodynia to mechanical stimulation and signs of spontaneous pain. Electrical stimulation of the contralateral VPL thalamic nucleus abolished the mechanical allodynia observed at the nerve ligated side. The effect of VPL stimulation outlasted the stimulation period by 15 min. No effect on the withdrawal thresholds at the control (sham operated) side was observed. These animals data support the clinical reports that stimulation of the sensory thalamus may alleviate pain of neuropathic origin. PMID- 8469410 TI - Effects of propentofylline, a NGF synthesis stimulator, on alterations in muscarinic cholinergic receptors induced by basal forebrain lesion in rats. AB - Basal forebrain (BF) lesions induced by ibotenic acid produced increases in the Bmax and Kd values of [3H]QNB binding sites in the frontal cortex, parietal cortex, and hippocampus. Twenty-eight-day successive administration of propentofylline (10 and 25 mg/kg, p.o.) significantly reduced the Kd values of [3H]QNB binding sites, to the levels of those in a sham group, in a dose dependent manner. Moreover, propentofylline (25 mg/kg, p.o.) significantly reduced the Bmax value of [3H]QNB binding sites compared with that in a vehicle treated BF-lesioned group. These results suggest that successive administration of propentofylline ameliorates changes in muscarinic cholinergic receptors through improving presynaptic cholinergic dysfunction. PMID- 8469412 TI - Dimethylsulfoxide (DMSO) blocks conduction in peripheral nerve C fibers: a possible mechanism of analgesia. AB - Dimethylsulfoxide (DMSO) is readily absorbed through skin, and relieves musculoskeletal pain when applied topically to painful areas. We studied the effects of DMSO on C-type nerve fibers, which mediate pain sensation. DMSO was applied directly to exposed cat sural nerves. C fiber conduction velocity was slowed by DMSO, even in low concentrations (5-7% v/v). Higher concentrations completely blocked C fiber conduction, with a minimum blocking concentration of 9%. Onset of nerve block was almost immediate with 15% DMSO or higher concentrations. C fiber blockade may account for analgesia with DMSO. PMID- 8469411 TI - Distribution of calcitonin gene-related peptide immunoreactive nerve fibers in the human submandibular gland. AB - The indirect immunofluorescence technique was used to study the distribution of calcitonin gene-related peptide (CGRP) in human submandibular gland. A relatively low number of thin varicose fibers with intense immunofluorescence for CGRP was seen in samples from seven glands. These CGRP-immunoreactive (CGRP-IR) nerve fibers were mainly seen around or in close contact with intra- and interlobular blood vessels. Some CGRP-IR nerve fibers were also found in association with intra- and interlobular salivary ducts and a few around the submandibular acini. By visual estimation there was no difference in the density of CGRP-IR nerve fibers between specimens of recurrent duct obstruction and laryngeal carcinoma. The present results show that the distribution of CGRP-IR nerve fibers in the stroma and in the glandular secretory elements of the human submandibular gland is quite similar to that seen in the rat and the ferret, which have been reported earlier. Furthermore, the regional distribution of CGRP-IR fibers in the human submandibular gland suggests that CGRP has a physiological role in the regulation of salivary gland function in human salivary glands, e.g. blood flow and secretion. PMID- 8469413 TI - Cellular localization of angiotensin type 1 receptor and angiotensinogen mRNAs in the subfornical organ of the rat brain. AB - The cellular localization of angiotensin type 1 receptor (AT 1) and angiotensinogen mRNA expression in the subfornical organ (SFO) of the rat brain has been studied by means of non-radioactive in situ hybridization combined with immunocytochemistry for glial fibrillary acidic protein (GFAP) and Neutral red staining. The AT 1 receptor mRNA expression is shown to be within putative nerve cells without any association with the glial fibrillary acidic protein (GFAP) immunoreactive (IR) cells. In contrast the angiotensinogen cRNA expression is associated predominantly with GFAP-IR cells. The results demonstrate that a neuronal AT 1 receptor mediates the actions of circulating angiotensin II on the SFO and that the angiotensinogen mRNA is predominantly expressed in the SFO astroglial cells. PMID- 8469414 TI - Diagnostic significance of skin immunolabelling with antibody against native cerebral amyloid in Alzheimer's disease. AB - Skin taken from patients with Alzheimer's disease (AD) and control patient groups were immunolabelled using antisera against either purified native cerebral beta protein or synthetic beta peptide. Native amyloid antiserum frequently labelled vascular walls in AD skin but rarely in control skin. Semi-quantitative analysis of the positive vessels showed a significant difference between the two groups. Sweat glands and dermal nerves were labelled in both groups. However, synthetic beta peptide antiserum showed no significant difference. Vascular wall labelling in skin with native amyloid antiserum is useful in the differential diagnosis of AD. PMID- 8469415 TI - Increased regional cerebral blood flow in inferior occipital cortex and cerebellum of early blind humans. AB - Cerebral flow indices were measured in 7 early blind and 13 sighted persons twice, during a task of passive and of active touch. In the blind, inferior occipital and cerebellar indices were higher. But they were not significantly modified by the kind of tactile task. PMID- 8469416 TI - Spinal cord localization of the motoneurons innervating the sacrococcygeus dorsi lateralis muscle and their noradrenergic nerve terminals in rats. AB - We examined in the present study the spinal cord localization of motoneurons innervating the caudal portion of the sacrococcygeus dorsi lateralis (SCDL) muscle and their noradrenergic nerve terminals in Sprague-Dawley rats, using horseradish peroxidase (HRP) and dopamine-beta-hydroxylase (DBH) double-labeling techniques. Retrogradely HRP-labeled motoneurons innervating the caudal part of the SCDL muscle were located ipsilaterally in the ventromedial aspect of the ventral horn (lamina IX) in spinal segments of S2-S4. These cells were polygonal in shape, with an average soma diameter of 37.0 +/- 1.1 microns (mean +/- S.E.M., n = 95) and amounted to 33.6 +/- 5.7 (n = 7) in the horizontal plane. Of note was the presence of abundant DBH-positive nerve terminals arborizing on the soma and dendrites of HRP-labeled motoneurons. These results provided anatomical evidence to further support our previous findings that the coerulospinal noradrenergic neurotransmission is involved in the mediation of fentanyl-induced muscular rigidity. PMID- 8469417 TI - The tonotopic representation in the auditory cortex of the guinea pig with optical recording. AB - We examined spatio-temporal characteristics of the tonotopic representation in the auditory cortex of the anesthetized guinea pig with a multichannel optical method using voltage-sensitive dye. The response latencies increased, and the response field in the cortex became small when the stimulus intensity levels were decreased. Low frequencies were represented rostrally and high frequencies caudally. The two fields responding to different frequencies at higher intensity levels gradually overlapped as time after stimulus onset increased, though these response field did not overlap at the beginning of the response. These findings indicate that tonotopic representation varies dynamically with time after stimulus onset. PMID- 8469418 TI - Ontogeny is different for explicit and implicit memory in humans. AB - This study was aimed to clarify in how far ontogenetic development is different for declarative/explicit compared to procedural/implicit learning. These two memory subsystems are differentially affected in a number of pathological conditions. Sixty-one children between the age of 5 and 10 years were tested on a verbal story recall and non-verbal pictorial recall task, representing explicit memory. To test for implicit memory, a motor mirror tracking task and a non-motor tower-of-hanoi puzzle were used. Both explicit memory tasks showed a clear developmental profile with an increase in the number of recalled items for immediate, late and delayed recall with adult values not reached before the age of 9-10 years. In contrast, there were no age differences for both implicit memory tasks. The study demonstrates that explicit and implicit memory follow different maturational trends and further corroborate the notion of two different memory systems. PMID- 8469419 TI - Adenosine A1 receptors in human hippocampus: inhibition of [3H]8-cyclopentyl-1,3 dipropylxanthine binding by antagonist drugs. AB - Adenosine A1 receptors were visualized in human hippocampus using [3H]8 cyclopentyl-1,3-dipropylxanthine (DPCPX) as a radioactive ligand probe. The receptor antagonists caffeine, the xanthine derivative KFM 19 and the carbamazepine analogue oxcarbazepine displaced [3H]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). Ki's in the individual layers were in a range between 8.5 +/- 6.5 microM and 18.9 +/- 16.0 microM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. Ki's could not be calculated for oxcarbazepine as the IC50's were greater than 100 microM with estimated IC25's varying between 51.2 +/- 53.3 microM and 179.9 +/- 89.9 microM. Antagonism of endogenous adenosine at A1 receptors may thus explain part of the clinical effects of caffeine in humans and possibly exclusively the behavioral effects of KFM 19 in non-human primates. PMID- 8469420 TI - Influence of interleukin-1 and tumor necrosis factor alpha on the growth of microglial cells in primary cultures of mouse cerebral cortex: involvement of colony-stimulating factor 1. AB - The influence of monokines and CNS-derived colony-stimulating factors (CSF) on the growth of microglia has been studied in mixed glial primary cultures stemming from mouse embryos. We observed that spontaneous growth of microglial cells in the presence of astrocytes is blocked by adding anti-colony-stimulating factor 1 (CSF-1) antibodies to the cultures. Both interleukin-1 (IL-1) and tumor necrosis factor-alpha(TNF alpha) strongly increased the number of microglial cells in mixed glial cultures and this effect was prevented by anti-CSF-1 antibodies. In contrast, anti-interleukin-3 (IL-3) or anti-granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies did not significantly affect the in vitro growth of microglia. These results provide functional significance to astrocytic productions of CSF-1 and their modulations by IL-1 or TNF alpha. PMID- 8469421 TI - Heart beat fluctuation during fictive locomotion in decerebrate cats: locomotor cardiac coupling of central origin. AB - Fictive locomotion was evoked by stimulation of the mesencephalic locomotor region (MLR) in immobilized, vagotomized and decerebrate cats. The coherence between heart beat fluctuation and efferent discharges of the hindlimb nerve was used to evaluate the strength of the coupling between the cardiac and locomotor rhythms during MLR-elicited fictive locomotion. This study demonstrated that there was a locomotor-cardiac coupling of central origin. PMID- 8469422 TI - Possible mutual excitatory couplings between inspiratory neurons in caudal ventrolateral medulla of brainstem-spinal cord preparation isolated from newborn rat. AB - In in vitro brainstem-spinal cord preparations, projection of inspiratory neurons in the caudal ventrolateral medulla (CVL) was examined electrophysiologically, and connectivity between bilateral inspiratory neurons in the CVL was analyzed by pulse-cross correlation (PCC) analysis. CVL inspiratory neurons were found to project to the contralateral CVL and/or mainly ipsilateral spinal cord. PCC analysis revealed significant peaks with different latency on both sides of time zero in 3 of 8 pairs. Results were consistent with mono- or oligo-synaptic excitatory connections between bilateral inspiratory neurons in the CVL. PMID- 8469423 TI - Localization of mRNA encoding the indolamine synthesizing enzyme, hydroxyindole-O methyltransferase, in chicken pineal gland and retina by in situ hybridization. AB - Hydroxyindole-O-methyltransferase (HIOMT) is the enzyme that catalyzes the final step in the synthesis of the hormone melatonin. We have examined the localization of expression of the mRNA encoding HIOMT by in situ hybridization in the 3-day old and adult chicken retina and pineal gland. The riboprobe utilized for this study was transcribed from the complete coding region of HIOMT cDNA synthesized from retina RNA and amplified by polymerase chain reaction (PCR). High levels of HIOMT mRNA were present in the pinealocytes of the pineal gland. In the retina, the hybridization signal was localized to the photoreceptors. The retinal photoreceptors of the 3-day-old chick displayed a much lower level of hybridization than did the photoreceptors of the adult chicken. This study strongly suggests that the photoreceptors are the sites of melatonin synthesis in the retina. PMID- 8469424 TI - The neuronal nuclear antigen recognized by the human anti-Ri autoantibody is expressed in central but not peripheral nervous system neurons. AB - Anti-Ri is a human autoantibody that recognizes a neuronal nuclear antigen (Ri). Biotinylated IgG from serum of two patients with high titers of anti-Ri antibodies was used to study the distribution of the Ri antigen in a panel of normal human tissues. the expression of the Ri antigen was evaluated by an avidin biotin peroxidase technique and confirmed by immunoblotting. The Ri antigen was restricted to the neurons of the central nervous system (CNS) and some pituitary cells. Most neurons in dorsal root, Gasserian and sympathetic ganglia, and myenteric plexus were negative or, a few of them, very weakly positive. The functional implication of the different expression of the Ri antigen between neurons of the central and peripheral nervous system is presently unknown. PMID- 8469425 TI - The ability of humans to localise noxious stimuli. AB - We have investigated the ability of humans to localise noxious stimuli on the dorsum of the hand. Pin-prick (non-penetrating needle prick), noxious heat (round 1 cm2 copper probe heated to 50 degrees C), mustard oil (100% applied topically in a small cotton ball, diameter 5 mm) and histamine (iontophoresis of 20 mC delivered to an area of 75 mm2) were applied to skin with intact innervation and during a differential nerve compression block of the superficial radial nerve when only C-fibres were conducting. The mean mislocalisation (+/- S.E.M.; n = 8) of all stimuli was 9.5 +/- 0.8 mm with normal nerve conduction and 8.9 +/- 1.2 during the differential nerve block. There was no significant difference between the noxious submodalities. By contrast, when nerve conduction was intact, purely tactile stimulation (7 mN von Frey hair) was significantly better localised having a mean error of 5.5 +/- 0.4 mm. We conclude that focal stimuli evoking itch or pain can be localised with high precision which is only marginally worse than for tactile stimuli. This suggests the existence of a somatotopical representation for noxious inputs in the brain similar to that found for tactile stimuli. PMID- 8469426 TI - Repeated seizures cause a generalized increase in excitability in the hippocampus. AB - Changes in excitability within the hippocampus were examined by recording in CA3 and in CA1 or the dentate gyrus and stimulating in the angular bundle (fiber bundle connecting the entorhinal cortex with the dentate gyrus) before and after 36 electrographic seizures in urethane anesthetized rats. The responses recorded in CA3 or CA1 to stimulation of the angular bundle every 30 s were unchanged after repeated seizures, while the responses in the dentate gyrus were augmented. When the angular bundle was stimulated every 200 ms, population spikes appeared in CA3 and CA1, with CA1 producing multiple population spikes before CA3. The results indicate that after repeated seizures there is a general enhancement of excitability throughout the hippocampus. PMID- 8469427 TI - Cerebrovascular NADPH diaphorase-containing nerve fibers in the rat. AB - Recently, neuronal nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase has been elucidated to be the nitric oxide synthase (NOS) per se. In order to examine the existence and distribution of cerebrovascular nerve fibers containing these substances, NADPH-diaphorase histochemistry was applied to the cerebral blood vessels and the cranial ganglia known to innervate the cerebral vessels in the rat. Numerous nerve fibers with varicosities forming plexuses were observed in the circle of Willis and its branches. In addition, thick nerve bundles were seen to run along the wall of the internal ethmoidal artery. NADPH-diaphorase reaction was prominent in neurons of the sphenopalatine, otic and internal carotid ganglia. This study demonstrated, for the first time, the NADPH diaphorase-containing nerve fibers in the cerebral vessels and ganglion cells in the parasympathetic and sensory ganglia known to innervate the cerebral vessels. PMID- 8469428 TI - Regulation of serotonin-induced calcium uptake in Spisula oocytes by tricyclic antidepressants. AB - The effect of tricyclic antidepressants on 5-hydroxytryptamine (serotonin or 5 HT)-induced maturation and Ca2+ uptake in Spisula oocytes was determined. The drugs at a concentration of 20 microM completely blocked germinal vesicle breakdown and 45Ca2+ uptake by Spisula oocytes. The order of effectiveness of the antidepressants were imipramine > desipramine > clomipramine. The present findings suggest that the action of tricyclic antidepressants is to regulate Ca2+ uptake into 5-HT-responsive cells. PMID- 8469429 TI - Degeneration of rat thalamic reticular neurons following intrathalamic domoic acid injection. AB - Domoic acid (DA), an analog of kainic acid, produces attentional deficits in humans who have ingested shell fish contaminated with this excitotoxin. The thalamic reticular nucleus (RT), by virtue of its location, connections and intrinsic properties, has been implicated in attentional processes. This study demonstrated the vulnerability of RT neurons following intrathalamic DA injections in rats. Lesions were characterized by almost total neuronal loss throughout the RT and sparing of adjacent populations of relay neurons in the VL and VPL. Los of RT neurons may underlie some types of attentional deficits observed in humans following DA poisoning. PMID- 8469430 TI - Human astrocytes and cytokines: tumor necrosis factor alpha and interferon gamma do not promote astrocytic proliferation. AB - Astrocyte cell cultures were established from human fetal brains and exposed to human recombinant tumor necrosis factor alpha (TNF alpha) and human recombinant interferon gamma (IFN gamma), and the proliferative response was assessed by bromodeoxyuridine-immunostaining technique. TNF alpha showed an inhibitory activity, while IFN gamma induced a slight increase in the number of astrocytes undergoing cell division. However, in both experiments differences were not statistically significant. Previous studies have demonstrated that TNF alpha and IFN gamma are potent mitogens for adult astrocytes in both in vivo and in vitro conditions. Our results suggest that in developing brain the immunomodulatory activity of cytokines, TNF alpha and IFN gamma, is different from that observed in adult brain. PMID- 8469431 TI - Facilitation of [3H]-ACh release by forskolin depends on A2-adenosine receptor activation. AB - The effect of forskolin (FSK) on [3H]-acetylcholine release ([3H]-ACh) from the phrenic motor nerve terminals, and its modification by adenosine deaminase (ADA), by the A2-adenosine receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N ethylcarboxamide adenosine (CGS 21680C), by the A1-adenosine receptor agonist R N6-phenylisopropyl adenosine (R-PIA), by the A2-antagonist N-(2-(dimethylamino) ethyl)-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3 -dipropyl-1H-purine-8-yl) benzene sulphonamide (PD 115,199), and by the A1-antagonist 1,3-dipropyl-8 cyclopentylxanthine (DPCPX) were studied on the rat phrenic-hemidiaphragm preparation. It is concluded that the excitatory effect of FSK on evoked [3H]-ACh release depends on tonic A2-adenosine receptor activation. PMID- 8469432 TI - Differential effects of dentate kindling on working and reference spatial memory in the rat. AB - An 8-arm radial maze was used to examine the effects of dentate kindling on the performance of a task which requires both working (short-term) and reference (long-term) memory. During the 4-week post-operative training period, control and experimental rats performed both components of the task equally well. Performance of the reference memory component, but not the working memory component of the task was significantly impaired during kindling stimulation. The impairment in reference memory appeared to be primarily due to the elicitation of afterdischarges, since the disruption in maze performance was evident in the pre convulsive stages of kindling. Following the cessation of kindling stimulation, a gradual recovery in reference memory performance was observed. Dentate kindling may provide a useful model for the study of long-term memory deficits associated with temporal lobe epilepsy. PMID- 8469433 TI - High-dose ketamine does not induce c-Fos protein expression in rat hippocampus. AB - The effects of high-dose ketamine on the c-fos protein (c-Fos) expression were investigated in rat by an immunohistochemical technique. The administration of 100 mg/kg ketamine i.p. induced seizure-like activity (limbic seizure). No c-Fos immunoreactivity was observed in hippocampus, piriform cortex and amygdala, while it was observed in neocortex and thalamus. These findings disagree with the reports that ketamine depresses the neuronal function of the neocortex and thalamus, while it stimulates the limbic system. PMID- 8469434 TI - Induction of c-Fos-like protein in the lateral habenular nucleus by persistent noxious peripheral stimulation. AB - Persistent noxious peripheral stimulation by formalin injection into the unilateral hindpad of anaesthetized rats induced c-Fos-like protein immunoreactivity (c-Fos-LI) in neurons within the lateral habenular nucleus (LHb) bilaterally. Formalin injection after the transection of spinal cords also induced c-Fos-LI in many neurons within the LHb, though the number of labeled cells changed depending on the post-transection period. These results suggest that the LHb modulates nociceptive information, but that it receives nociceptive information via extraspinal pathways as well as intraspinal ascending noxious pathways. PMID- 8469435 TI - Sex differences in the anteroventral periventricular nucleus of the preoptic area and in the related effects of androgen in prenatal rats. AB - The density of cells in the anteroventral periventricular nucleus (AVPv) of the preoptic area of female rats was greater than that of males on day 21 of gestation. It appears that this difference between the sexes is caused by the action of androgen since the density of cells in the AVPv of female fetuses fell to the density in males when the mother received injections of testosterone propionate (TP) on days 14-18 of gestation. Pycnotic cells were more frequently found in oil-treated control males and TP-treated female fetuses than in control female fetuses. This result suggests that the prenatal injections of TP enhanced the rate of degeneration of the cells in the AVPv. PMID- 8469436 TI - Autoradiographic demonstration of an increase in muscarinic cholinergic receptors in cerebellar granule cells treated with tetrahydroaminoacridine. AB - The neurotrophic and neurosurviving effects of 9-amino-1,2,3,4-tetrahydroacridine (THA), a putative antidementia agent, were studied in cultured granule cells using biochemical and morphological methods. The addition of 30 microM THA to cultures grown in 15 mM K(+)-containing media markedly increased cell survival and enhanced [3H]N-methylscopolamine binding to muscarinic cholinergic receptors (mAChRs). Furthermore, receptor autoradiographic studies revealed that neuronal cells were labelled over both cell bodies and fibers by the [3H]receptor ligand. These observations provide direct evidence that THA promotes the expression of mAChR binding sites in differentiating cerebellar granule cells. PMID- 8469437 TI - Differential fatty acid release from CA1 and CA3 regions of rat hippocampal slices under hypoxia and hypoglycemia. AB - Rat hippocampal slices were subjected to hypoxia and/or hypoglycemia for 10 min, and free fatty acids released in CA1 and CA3 regions were separately analyzed. Fatty acid accumulation in CA1 was not so significant under hypoglycemia, but very prominent under hypoxia. Free fatty acid levels in CA3 were much less than those in CA1 even under hypoxia plus hypoglycemia. This observation seems to be consistent with the selective vulnerability of CA1 neurons seen in in vivo ischemia. The decreasing order of accumulation of free fatty acid species in CA1 was C16:0 > C18:0 > C18:1 > C20:4 > C22:6. The increment fold as compared to control level was decreasing as follows: C22:6, 28 times; C20:4, 13 times, C18:1, 10 times; C18:0 = C16:0, 3 times. The present experimental conditions using hippocampal slices provided a good in vitro model to prove the selective hypoxic damages of the CA1 subfield in terms of free fatty acid release in association with the membrane degradation. PMID- 8469438 TI - Hormonal influence on the permeability of the blood-brain barrier: effect of an analog of adrenocorticotropic hormone, beta 1-24 corticotrophin. AB - Regional unidirectional transport of alpha-aminoisobutyric acid (AIB) (mol. wt.: 104) and sucrose (mol wt.: 342) which have a low permeability across the intact endothelium was investigated in brain of rats either treated with synacthene: an analog of ACTH, tetracosactide retard (beta-1-24 corticotrophin) or in brain of placebo-treated controls. Three days treatment with synacthene, reduced the rate of influx of AIB and sucrose in most of the brain regions studied especially in thalamus, hypothalamus, cortex, and caudate nucleus without affecting the vascular compartment. The brainstem, cerebellum and white matter were less affected. These experimental findings may suggest that ACTH exhibits significant influence on hormonal regulation of blood-brain barrier permeability. Thereby such a regulation may involve the entry of polar compounds into the CNS and may influence the central effects of diffusion-limited drugs. PMID- 8469439 TI - Alterations of glial fibrillary acidic protein mRNA level in the aging brain and in senile dementia of the Alzheimer type. AB - The GFAP mRNA levels were compared to the density of the senile plaques (SP) in postmortem brain samples of 8 cases, either non-demented or affected by senile dementia of the Alzheimer type. In the frontal neocortex, the GFAP mRNA level is not affected, even if SP are present. In the temporal neocortex, a positive correlation between GFAP mRNA level and SP density was highly significant. This shows that in this area, astrocytes are altered at transcriptional or post transcriptional levels, or both. The different responses of this astrogliosis marker in each area may be related to the loss of specific neurotransmitter system. PMID- 8469440 TI - Lamellated receptors in the skin of the hagfish, Myxine glutinosa. AB - The adult hagfish, Myxine glutinosa, does not exhibit a lateral line system. The hypodermal layer of the dorsal head and body skin contains a prominent receptor system--lamellated corpuscles--arranged in a segmental pattern close to the body fascia. The topography and the structural organization of the lamellated receptors are described at the light- and electronmicroscopical levels. Spinal nerves supply the lamellated receptor organs. A mechanoreceptive function and evolutionary aspects are discussed. PMID- 8469441 TI - Antinociceptive activity of salmon calcitonin: electrophysiological correlates in a rat chronic pain model. AB - Experimental and clinical evidence testifies to an antinociceptive action of salmon calcitonin (sCT), administered in different ways, on the central nervous system. These studies were performed almost exclusively in acute pain models. The purpose of the present study was to investigate the effects of sCT, injected directly into the lateral cerebral ventriculi, on the firing of single nociceptive thalamic neurons, detected by electrophysiological techniques in an experimental model of prolonged or chronic pain, such as rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of sCT (5, 10, 20, 40 micrograms, 5 microliters/i.c.v.) it was possible to observe correspondingly increasing inhibitory and long-lasting effects on the evoked firing, with a significant dose effect relationship. In agreement with electrophysiological findings, preliminary data, obtained with a patch clamp technique, on depression of calcium fluxes through neuronal membrane, induced by sCT, oriented the attention to a direct action of sCT on CNS. PMID- 8469443 TI - Detection of thyrotrophin releasing hormone in rat brain in vivo using novel antibody microprobes: effects of amphetamine. AB - Antibody microprobes of novel design were used to monitor thyrotrophin releasing hormone (TRH) in rat brain before and after-parenteral administration of amphetamine. Specific antibodies to TRH were bound to the outside of glass microprobes by adsorption to a surface of activated charcoal embedded in epoxylite resin. In male Wistar rats anaesthetised with chloral hydrate a series of antibody microprobes were implanted in forebrain. Amphetamine (10 mg/kg i.p.) caused a highly significant decrease in the binding of 125I-TRH to microprobes, indicating an increase in extracellular TRH localised in the lateral septum. There was also evidence of TRH release in the septo-hypothalamic nucleus. Neither saline, nor amphetamine at 2 mg/kg were able to evoke changes in the release of TRH at any sites. PMID- 8469442 TI - Adenosine 5'-triphosphate release from the normoxic and hypoxic in vivo rat cerebral cortex. AB - The release of adenine nucleotides and adenosine from the in vivo rat cerebral cortex has been measured in the presence of DL-alpha-glycerophosphate (10(-2) M), an inhibitor of non-specific phosphatases. In normoxic brains, the superfusate concentrations of adenosine and its nucleotides (in nM) were: adenosine 38.9 +/- 10.9; AMP 13.9 +/- 1.6; ADP 12.4 +/- 2.3; ATP 17.7 +/- 2.1. During 10 min episodes of hypoxia (8% oxygen inhalation) superfusate levels of adenosine doubled, but the release of nucleotides was unaltered. These findings indicate that extracellular levels of ATP in the cerebral cortex are in the range at which this compound dilates cerebral blood vessels, and that ATP may be an endogenous regulator of regional cerebral blood flow. The absence of any increase in nucleotide levels during hypoxic episodes implies that adenosine is released into the extracellular space as the nucleoside, and not as a nucleotide which would then be hydrolyzed to adenosine. PMID- 8469444 TI - Managing a multisystem interactive video laboratory. PMID- 8469445 TI - Nationwide computerized NCLEX, April, 1994! Will you be ready? PMID- 8469446 TI - Optimizing use of a hospital computer lab. PMID- 8469447 TI - Perceptions, concerns and needs that influence technology integration. PMID- 8469448 TI - Mutation and overexpression of p53 in early-stage epithelial ovarian cancer. AB - OBJECTIVE: To investigate whether mutation and overexpression of p53 is a feature of early-stage ovarian cancers. METHODS: Because early-stage ovarian cancers are relatively uncommon, we adapted p53 immunostaining and DNA sequencing methods for use in paraffin-embedded tissue blocks. Early-stage ovarian cancers from 52 patients treated at Duke University between 1980-1991 were analyzed. RESULTS: Immunostaining for p53 consistent with overexpression was seen in 29% of early stage (I/II) ovarian cancers overall. The incidence of p53 overexpression was lower in cancers confined to the ovaries (stage IA/IB) (15%) than in cancers that had spread outside the ovaries (stage IC/II) (44%) (P = .03). Although p53 overexpression was seen more frequently in large tumors (diameter greater than 10 cm) and in tumors with "high-risk" features (stage IC or II, or grade 3), these relationships were not statistically significant. Recurrent disease developed in 35% of the patients in this series, but there was no relationship between p53 overexpression and recurrence rate or survival. The presence of point mutations in the p53 gene was confirmed by DNA sequencing in eight cancers that overexpressed p53. CONCLUSION: Mutation and overexpression of p53 are less frequent in early-stage ovarian cancers than in advanced-stage cases. P53 overexpression is not associated with adverse outcome in early-stage ovarian cancer. PMID- 8469449 TI - Profiles of women age 30-39 and age less than 30 with epithelial ovarian cancer. AB - OBJECTIVE: To study a group of women diagnosed with epithelial ovarian cancer at a young age (less than 40). METHODS: Tumor registry data were analyzed with respect to age at diagnosis, stage, grade, frequency of nulligravidity, and family history of breast or ovarian cancer. Frequencies were analyzed using contingency tables, and survival distributions were analyzed according to the method of Kaplan and Meier. Multivariate survival analysis was performed with the Cox method. RESULTS: We found significantly higher frequencies of low-grade tumors (90 versus 37%; P = .0003, chi 2 test) and early-stage tumors (45 versus 17%; P = .03, Fisher exact test) in women less than 30 at the time of diagnosis (very young patients) than in those between 30-39. We also found a significant (P = .017, Breslow statistic) survival advantage for the very young women. Multivariate analysis demonstrated tumor grade as the independent variable for survival. CONCLUSION: These findings support the concept of a preclinical phase of epithelial carcinoma and show that young women may derive substantial benefit from ovarian cancer screening programs. PMID- 8469450 TI - Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. AB - OBJECTIVE: To assess the estrogenic effect of tamoxifen and associated pathologic changes of the endometrium in postmenopausal breast cancer patients. METHODS: The endometrium of 103 gynecologically asymptomatic postmenopausal breast cancer patients was examined. Fifty-one had been treated with tamoxifen and 52 had not received any hormonal treatment. The two groups were similar in age, parity, age at menopause, and body mass index. RESULTS: Compared with the control subjects, the tamoxifen patients had a thicker endometrium (mean +/- standard deviation 10.4 +/- 5.0 versus 4.2 +/- 2.7 mm; P = .0001) and larger uterine volume (45 +/- 27 versus 25 +/- 11 cm3; P = .001), as determined by transvaginal sonography. Hysteroscopy showed an atrophic endometrium in 28% of the patients in the tamoxifen group, as compared with 87% of the control patients (P = .0001). Endometrial polyps were more frequent in the tamoxifen group (36 versus 10%; P = .004), which included one patient with atypical hyperplasia, one with adenomatous hyperplasia, and one with endometrial adenocarcinoma; two controls had endometrial adenocarcinoma. CONCLUSION: The results provide evidence for an estrogenic effect of long-term tamoxifen treatment on the postmenopausal uterus and show it to be associated with an increased occurrence of polyps. PMID- 8469451 TI - Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity. AB - OBJECTIVE: To evaluate the correlation between natural killer cell activity and serum estradiol (E2) levels in patients with different stages of endometriosis. METHODS: Natural killer cell activity of peripheral blood lymphocytes and serum E2 levels were evaluated in 73 women who underwent laparoscopy for pelvic pain, infertility, and benign adnexal masses. RESULTS: The 33 patients (45%) with endometriosis showed a significant decrease in natural killer cell activity in relationship to an increase in disease stage (correlation coefficient r = -0.83, P < .001). A significant inverse relationship was observed between cytotoxicity and serum E2 levels (correlation coefficient r = -0.89, P < .001). CONCLUSION: The relationship between natural killer cell activity and serum E2 levels suggests that an immunoendocrine interaction plays an important role in the progression of endometriosis. PMID- 8469452 TI - Bone density is compromised in amenorrheic women despite return of menses: a 2 year study. AB - OBJECTIVE: To determine the effects of estrogen deprivation on bone mass in young women in whom large bone mass increases are known to occur. METHODS: Over 2 years, nine amenorrheic and 21 normal women were studied, classified into exercising (dancers) and sedentary subjects. An integrated estrogen exposure score was used to determine estrogen response during the 2 years of study. Bone mineral density was measured by single and dual photon absorptiometry in the spine, wrist, and foot (metatarsus). RESULTS: Hypoestrogenism was present in all amenorrheic women in the first year, and mean estrogen exposure scores were lower in these subjects during the 2 years. Mean spine, wrist, and metatarsal bone mineral density measurements were lower in the amenorrheic women and remained below the levels in controls, despite changing clinical indices and return of menses in some of the subjects. Amenorrheic dancers showed the greatest increase in spine bone mineral density, gaining 9.65% in the first year, 4.49% in the second, and an increase of 14.43% (P < .05) over the total period. Their bone mineral density values, however, remained significantly below those of normal controls during the duration of the study. The most significant gains were seen in two subjects with weight gain and return of irregular periods (three periods in 12 months). CONCLUSION: Young amenorrheic exercising women appear to increase bone mass before the return of normal menses; however, bone mass remained below control values during 2 years of study, possibly because of long-term adolescent hypoestrogenism. PMID- 8469453 TI - Prenatal diagnosis of congenital heart disease and fetal karyotyping. AB - OBJECTIVE: To determine the incidence of aneuploidy among fetuses with congenital heart disease diagnosed in utero. METHODS: From June 1988 through December 1991, 502 fetuses at risk for congenital heart disease underwent fetal echocardiography. Fetal karyotyping was performed whenever a cardiac anomaly was diagnosed. Autopsy reports, postnatal echocardiograms, and angiograms were obtained to confirm the diagnosis. RESULTS: Congenital heart disease was found in 31 of 469 fetuses with complete follow-up. Fifteen of these 31 fetuses (48%) were found to have an abnormal karyotype: five of 17 (29.4%) with isolated cardiac anomalies and ten of 14 (71.4%) with cardiac and extracardiac anomalies. Detected chromosomal abnormalities included six trisomy 21, four trisomy 18, four trisomy 13, and one triploidy 69,XXX. Atrioventricular septal defects and ventricular septal defects were the cardiac malformations most often associated with abnormal karyotypes (77 and 71%, respectively). CONCLUSIONS: The risk of aneuploidy associated with fetal cardiac anomalies is much greater than that associated with elevated maternal age; therefore, fetal karyotyping should be offered whenever a cardiac defect is diagnosed. Advanced gestational age should not represent a deterrent, because the discovery of a lethal trisomy in a fetus with a cardiac malformation can affect dramatically the prognosis and the obstetric and neonatal management. We believe that a screening view such as the four-chamber view should now be included routinely in obstetric ultrasound examinations. PMID- 8469454 TI - The difference between septated and nonseptated nuchal cystic hygroma in the early second trimester. AB - OBJECTIVE: To compare nonseptated and septated cystic hygromas in terms of morphologic appearance and prognosis. METHODS: During a 5-year period, 125 cases of nonseptated cystic hygroma were detected by transvaginal sonography among 7582 sonographic fetal scans (1.6%) in the first and early second trimesters. Twenty five cases of septated cystic hygroma were detected in the same population. Fetal karyotype abnormalities; sonographic, morphologic, and histologic appearance; and pregnancy outcome were compared between the groups. RESULTS: Whereas 98% of the nonseptated cystic hygromas were transient, only 44% of the 25 septated cystic hygromas were transient. Six of the 106 cases of nonseptated cystic hygroma that underwent karyotyping were dyskaryotic (5.7%), compared with a 72% (18 of 25) aneuploidy rate in the septated cystic hygromas. Only two cases of hydrops fetalis (1.7%) occurred among the nonseptated cystic hygromas, versus 40% (ten of 25) in the septated cystic hygromas. Fifteen percent of the nonseptated cystic hygromas had associated anomalies (17 of 115) versus 52% (13 of 25) in the septated counterpart. As compared with the septated group, the nonseptated cystic hygromas had a different sonographic, morphologic, and histologic appearance. The live-birth rate was 94% (108 of 115) in the nonseptated cystic hygromas, versus only 12% in the septated group. CONCLUSIONS: This study confirms our previous suggestion that nonseptated cystic hygromas differ from septated lesions, not only in location and morphologic appearance, but also in prognosis. PMID- 8469455 TI - Obstetric correlates of neonatal retinal hemorrhage. AB - OBJECTIVE: To determine whether maternal or fetal factors, other than vacuum assisted delivery, play a role in neonatal retinal hemorrhage, and whether correlates are similar in retinal hemorrhage after spontaneous vaginal delivery. METHODS: A cross-section of assisted deliveries at an urban hospital (n = 156) over 7 months were compared with contemporaneous spontaneous vaginal deliveries (n = 122). A subset of assisted deliveries (n = 87) was prospectively randomized to forceps or vacuum-assisted delivery by sealed envelope. Maternal and neonatal biometric data were collected, and Apgar scores, umbilical artery blood gas analysis, and neonatal ophthalmologic evaluations were performed. RESULTS: Moderate to severe retinal hemorrhage was found in 18% of spontaneous, 13% of forceps, 28% of vacuum-assisted, and 50% of sequential vacuum and forceps assisted deliveries. Fetal distress (P < .008), vacuum-assisted delivery (P < .02), decreased birth weight for gestation (P < .004), umbilical artery pH less than 7.20 (P < .004), and second stage of labor less than 30 minutes (P < .05) were most closely associated with increased degrees of retinal hemorrhage. Maternal parity, preeclampsia, length of labor, and head circumference were not correlated with retinal hemorrhage. Vacuum-assisted delivery among low birth weight infants (P < .0001), short second stage of labor (P < .006), fetal acidosis (P < .045), and sequential use of vacuum and forceps for assisted delivery (P < .005) formed a logistic model that correctly predicted 81% of moderate to severe retinal hemorrhage cases. Logistic analysis of the randomized assisted deliveries gave similar results. CONCLUSIONS: Maternal and fetal factors other than vacuum-assisted delivery are significant correlates of moderate to severe retinal hemorrhage. Vacuum-assisted delivery among small for gestational age infants is closely correlated with moderate to severe retinal hemorrhage. PMID- 8469456 TI - Intrapartum prediction of birth weight: clinical versus sonographic estimation based on femur length alone. AB - OBJECTIVE: To determine the relative accuracy of predicting birth weight by clinical estimate versus sonographic mensuration of femur length (FL) alone. METHODS: Two hundred pregnant women at term and in early labor had the weight of their fetuses estimated by clinical and sonographic methods. RESULTS: Clinical assessment of birth weight had a significantly lower mean standardized absolute error (90.6 g/kg) than sonographic estimate based on FL alone (106.7 g/kg) (P < .05). Clinical estimates were significantly more often within 5% (35%) of actual birth weight than were those derived sonographically (29%) (P = .005). CONCLUSION: Using FL alone to predict birth weight has no advantage over a clinical estimate among term patients in labor. PMID- 8469457 TI - Amniotic fluid volume estimation in the postdate pregnancy: a comparison of techniques. AB - OBJECTIVE: To determine the amniotic fluid (AF) volume estimation technique with the greatest diagnostic value with respect to perinatal outcome in the postdate pregnancy. METHODS: One hundred ninety-eight women who were at least 40 weeks' gestation based on ultrasound confirmation or establishment of dates were evaluated twice weekly with nonstress tests (NSTs) and AF volume estimation. Various indices of AF volume were measured and correlated with perinatal outcome. Receiver operating characteristic curves were used to determine optimal cutoff values. RESULTS: There was a significantly larger maximal vertical pocket in those pregnancies with a normal perinatal outcome than in those with abnormal outcome (4.2 +/- 1.4 versus 3.2 +/- 2.0 cm; P = .02). A statistically significant difference was also seen with the AF index (10.0 +/- 4.5 versus 7.5 +/- 5.0 cm; P = .01). Analysis revealed that the optimal cutoff for identifying clinically significant oligohydramnios was a largest vertical pocket less than 2.7 cm, with an adjusted odds ratio for abnormal perinatal outcome of 7.11 (95% confidence interval [CI] 2.79-18.16). Its sensitivity of 50.0% and specificity of 87.9% were superior to the diagnostic value of the AF index of 5 cm, which had a sensitivity of 29.2% and specificity of 89.1%. CONCLUSION: A largest vertical pocket threshold of 2.7 cm had the greatest diagnostic value for identifying the postdate pregnancy at risk for abnormal perinatal outcome, surpassing the AF index and the 2-cm largest vertical pocket rule. PMID- 8469458 TI - Reproductive outcome after 143 laparoscopic procedures for ectopic pregnancy. AB - OBJECTIVE: To analyze reproductive outcome after laparoscopic procedures for ectopic pregnancy, with particular attention to laparoscopic salpingectomy. METHODS: In a 260-physician multispecialty clinic in the rural upper midwestern United States, 143 patients were followed prospectively after undergoing laparoscopic procedures for ectopic pregnancy. Ninety-five who sought further pregnancies during the study period were analyzed for reproductive outcome. Intrauterine pregnancy rates were compared by age, parity, size of ectopic gestation, and evidence of prior tubal damage. Life table analysis was also performed. RESULTS: The overall intrauterine pregnancy rates for laparoscopic salpingostomy (60%) and laparoscopic salpingectomy (54%) were not significantly different from each other. However, intrauterine pregnancy rates differed significantly by history of prior tubal damage. The pregnancy rate was 79% among women without tubal damage and 42% among women with damage. CONCLUSIONS: Our intrauterine pregnancy rates after both laparoscopic salpingectomy and laparoscopic salpingostomy are similar to those reported in the literature for similar procedures performed at laparotomy. In predicting pregnancy outcome after laparoscopic procedures for ectopic pregnancy, the major variable seemed to be evidence of prior tubal damage. With no evidence of previous damage, we found similarly high pregnancy rates for laparoscopic salpingostomy and salpingectomy. PMID- 8469459 TI - Hysteroscopic treatment of menorrhagia associated with uterine leiomyomas. AB - OBJECTIVE: To determine the effectiveness of hysteroscopic treatment of menorrhagia associated with uterine leiomyomas. METHODS: Fifty-one women with uterine myomas were treated for menorrhagia by hysteroscopic resection with or without endometrial ablation. Patients were followed for 1-5 years after treatment. RESULTS: The mean number of pads used during the heaviest day of menses decreased from 17.8 before treatment to 6.8 after treatment (P < .005) in women undergoing resection only, and from 21.4 to 1.7 pads per day in women whose treatment included endometrial ablation (P < .001). Two-thirds of the women who underwent ablation were completely amenorrheic after the procedure. Both groups experienced significant decreases in dysmenorrhea. Three patients subsequently underwent hysterectomy after hysteroscopic treatment, and one required a repeat hysteroscopic procedure. CONCLUSION: Hysteroscopic treatment of menorrhagia associated with uterine myomas can be effective in carefully selected patients. PMID- 8469460 TI - Epidemiologic characteristics of women with idiopathic recurrent vulvovaginal candidiasis. AB - OBJECTIVE: To evaluate risk factors related to anamnestic variables, sexual behavior, feminine hygiene habits, and microbiologic findings in women with idiopathic recurrent vulvovaginal candidiasis. METHODS: We conducted a multivariate observational study comparing sociodemographic, anamnestic, clinical, and microbiologic variables between 86 patients with recurrent vaginal candidiasis and 180 controls with nonrecurrent infection. RESULTS: In logistic regression analysis, women with recurrent candidal vaginitis were more likely than controls to use contraceptive pills (adjusted odds ratio 2.0, 95% confidence interval [CI] 1.02-3.91; P = .04) and commercially available solutions for either vulvoperineal cleansing (adjusted odds ratio 2.2, 95% CI 1.25-3.88; P = .007) or vaginal douching (adjusted odds ratio 1.8, 95% CI 1.0-3.26; P = .05). The rate of isolation of non-albicans candida species was significantly higher among cases than controls (adjusted odds ratio 3.0, 95% CI 1.50-6.04; P = .005). Finally, increasing frequency of monthly sexual intercourse was significantly correlated (chi 2 for trend = 4.87; P = .027) with recurrent infection. CONCLUSION: Several behavioral factors seem to influence the occurrence of relapses in recurrent vulvovaginal candidiasis. Appropriate counseling about contraception, sexual activity, and personal hygiene habits could be an important preventive measure in these cases. PMID- 8469461 TI - Chlamydia trachomatis in patients who used oral contraceptives and had intermenstrual spotting. AB - OBJECTIVE: To identify the incidence of positive assays for direct antigen detection of Chlamydia trachomatis in oral contraceptive (OC) users with and without intermenstrual spotting and in women seeking contraception. METHODS: We studied 65 women who had used OCs for more than 3 months and who presented with intermenstrual spotting for which no readily demonstrable cause could be identified. They were compared with 65 matched controls who were taking OCs without intermenstrual spotting and who had chlamydia testing because of one or more risk factors, and 65 matched controls seeking contraception. The incidence of positive tests for each group was compared by chi 2 test for independence using the Yates formula. The strength of the relationship was analyzed by determining the Craemer phi coefficient. RESULTS: Nineteen of the 65 women (29.2%) taking OCs for more than 3 months and experiencing bleeding had positive tests, in contrast to seven of 65 matched controls (10.7%) who were also on OCs and who had had chlamydia testing because of vaginitis or new or multiple sexual consorts, and four of 65 women (6.1%) who were screened for C trachomatis before initiation of contraception. The significance level for the chi 2 statistic was P < .01. CONCLUSION: Intermenstrual bleeding in women previously well regulated on OCs appears to be an added marker for chlamydial infection. PMID- 8469462 TI - Diagnosing proximal tubal obstruction: evaluation of peak intrauterine pressures using four common cannula techniques in extirpated uteri. AB - OBJECTIVE: To compare the ability of four chromotubation techniques to generate and maintain intrauterine pressures in the diagnosis of proximal tubal obstruction. METHODS: Sixteen extirpated uteri were used for this study. A pressure catheter was placed through the fundus into the endometrial cavity. Three cannulas were evaluated: 1) the Cohen cannula with hold and no-hold techniques, 2) the BARD cervical cannula (dual intrauterine and intracervical balloons), and 3) the Harris-Kronner uterine manipulator-injector catheter with an intrauterine balloon. Intrauterine pressures were monitored while warm saline was infused. The studies were performed with the tubes obstructed, and measurements of peak attainable intrauterine pressures were recorded. Data were analyzed by t test, with significance set at P < .05. RESULTS: Peak intrauterine pressures for the four groups were as follows: 1) Cohen cannula, not holding, 40.7 +/- 5.1 mmHg; 2) Cohen cannula, holding in place, 63.6 +/- 5.3 mmHg; 3) BARD cannula, 112.4 +/- 3.5 mmHg; and 4) Harris-Kronner cannula, 106.3 +/- 4.3 mmHg. The BARD and Harris-Kronner cannulas achieved significantly higher intrauterine pressures than either method of using the Cohen cannula (P < .001). There was no statistically significant difference between the BARD and Harris-Kronner cannulas. CONCLUSION: Significant differences in achievable intrauterine pressures were demonstrated among catheters in our in vitro model. Based on these findings, we believe that the BARD, Harris-Kronner, or other intrauterine balloon type cannula should be used before diagnosing proximal tubal obstruction. PMID- 8469463 TI - The utility of a home urinary LH immunoassay in timing the postcoital test. AB - OBJECTIVE: To evaluate whether a urinary LH immunoassay improves timing of the postcoital test compared to traditional timing methods in normally ovulating women. METHODS: Subjects included 37 infertile couples evaluated in a tertiary care setting. A randomized, prospective trial was performed of two methods of postcoital test timing: urinary LH assay or the traditional timing by cycle averaging and/or review of basal body temperature graphs. RESULTS: Similar serum estradiol, progesterone, LH, number of motile sperm per high-power field, cervical mucus scores, and postcoital test scores were identified in both groups. CONCLUSION: Urinary LH immunoassays do not appear to improve timing of the postcoital test as compared with traditional timing methods. PMID- 8469464 TI - Terbutaline tocolysis and glucose intolerance. AB - OBJECTIVE: To determine whether there is an increased incidence of glucose intolerance in association with chronic terbutaline therapy, administered either orally or as a continuous subcutaneous infusion. METHODS: Sixty-nine women received terbutaline, orally (38 subjects) or as a continuous subcutaneous infusion (31 subjects). Their gestational diabetes screening results were compared to the results in 82 women not receiving beta-mimetic therapy. RESULTS: Subjects receiving terbutaline had significantly higher mean glucose concentrations after the 1-hour 50-g glucose tolerance test (GTT) than did controls (P < .05, one-way analysis of variance with multiple comparisons). Among subjects receiving a continuous subcutaneous infusion of terbutaline, the incidence of abnormal 3-hour 100-g GTT results was higher than among controls (20 versus 4%; P = .023 by chi 2). CONCLUSIONS: The incidence of GTT abnormalities is increased among women receiving terbutaline. We recommend surveillance of glucose tolerance among patients receiving terbutaline chronically, regardless of the route of administration. PMID- 8469465 TI - Confirming the safety of transvaginal sonography in patients suspected of placenta previa. AB - OBJECTIVE: To evaluate the safety of transvaginal ultrasonography in the diagnosis of placenta previa by determining whether the angle between the cervix and the vaginal probe is sufficient for alignment of the probe with the cervix. METHODS: The angle between the axis of the cervix and that of the vaginal probe (the axis of the vagina) was measured from copies of the transvaginal ultrasound examinations of 18 patients with documented placenta previa past 20 weeks' gestation. The measurements were compared with those of gestationally matched controls without placenta previa. RESULTS: The mean angles were 63.8 degrees and 67.5 degrees, with minimum angles of 44 degrees and 48 degrees for the placenta previa and control groups, respectively. The values were not statistically different. CONCLUSION: These findings strengthen the previously undocumented presumption that the angle between the cervix and vaginal probe is sufficient to prevent the probe from inadvertently slipping into the cervix. Therefore, this study supports the safety of transvaginal sonography in diagnosing and monitoring patients with known placenta previa. PMID- 8469466 TI - Double-blind randomized study comparing amoxicillin and erythromycin for the treatment of Chlamydia trachomatis in pregnancy. AB - OBJECTIVE: To compare the efficacy and patient tolerance of amoxicillin to that of erythromycin in the treatment of lower genital tract chlamydia infections during pregnancy. METHODS: A double-blind, randomized study was conducted comparing oral amoxicillin 500 mg three times daily versus oral erythromycin 500 mg four times daily for 7 days. One hundred forty-three women with positive cervical cultures for chlamydia at less than 36 weeks' gestation were enrolled. A test-of-cure culture was obtained 4 weeks after entry into the study and side effects were assessed. Success of the regimen was defined as completing the course of medication and having a negative test-of-cure culture. RESULTS: Thirty of the 65 women in the erythromycin group (46.1%) developed symptoms while taking the medication and 15 of them were unable to continue treatment (23.1%). In contrast, five of the 65 women (7.7%) in the amoxicillin group became symptomatic, with only one of these patients intolerant of the side effects (1.5%) (P < .001). Of the 50 patients in the erythromycin group who were able to complete their course of medication, only three had a positive test of cure (6.0%). In comparison, nine of the 64 patients (14.1%) taking amoxicillin who completed their course had positive cultures at test of cure. This difference was not statistically significant (P = .14). Forty-seven of the 65 patients (72.3%) in the erythromycin group successfully completed their regimen, compared to 55 of the 65 women (84.6%) in the amoxicillin group. This difference was not statistically significant. CONCLUSIONS: These findings suggest that amoxicillin is a reasonable alternative for the treatment of chlamydia in pregnant patients intolerant to erythromycin. The incidence of side effects and intolerance to therapy for amoxicillin are less than those for erythromycin. PMID- 8469467 TI - Clinical and environmental predictors of preterm labor. AB - OBJECTIVE: To determine the magnitude of risk for preterm labor associated with specific clinical and environmental factors. METHODS: Using a case-control design, 266 women with preterm labor and 512 controls were interviewed and their medical records reviewed. Crude and adjusted odds ratios were calculated for each risk factor. Population-attributable risks were estimated. RESULTS: Third trimester bleeding, twin gestation, and chorioamnionitis at presentation were strongly associated with preterm labor (odds ratios 11.2-48.3). A history of a prior preterm delivery, vaginal bleeding in the first or second trimester, maternal diethylstilbestrol exposure, uterine anomalies, and urinary tract infection during pregnancy were associated to a lesser extent (odds ratios 1.6 5.4), as were cigarette smoking and drug use (odds ratios 2.0 and 3.0). Cases who had preterm labor preceded by premature rupture of the membranes had a substantially higher risk of preterm labor if chorioamnionitis, vaginal bleeding early in pregnancy, or urinary tract infection was present. By contrast, women who had intact membranes at the onset of preterm labor carried higher risk when twin gestation, placental abruption, or uterine anomaly was present. The highest population-attributable risks for preterm labor were found in patients with a twin gestation or third-trimester bleeding. CONCLUSIONS: Programs to reduce the preterm delivery rate should consider the attributable risks for the factors they are intended to modify. The attributable risks we obtained suggest that medical strategies to reduce the impact of the clinical variables, especially multiple gestation, and educational programs to decrease smoking and drug use should reduce the preterm delivery rate. PMID- 8469468 TI - Active-phase arrest in labor: predictors of cesarean delivery in a nulliparous population. AB - OBJECTIVE: To identify clinical variables associated with cesarean delivery for active-phase arrest with hypotonic labor. METHODS: We reviewed all deliveries at our institution from September 1975 through March 1989. Data were collected from medical records and a computerized data base. Nulliparas with active-phase arrest were identified and those with hypotonic labor (defined as less than 180 Montevideo units) were selected. The clinical characteristics of each parturient were examined. A linear logistic regression analysis was used to examine the incidence of cesarean delivery as a function of clinical variables. RESULTS: The incidence of active-phase arrest was 4.9%, and hypotonic forces were diagnosed in 81% of the cases managed with an intrauterine pressure catheter. Despite the consistent use of oxytocin in hypotonic labor, the cesarean rate was 60%. Four factors correlated with cesarean delivery in this setting: estimated fetal weight, station at the time of arrest, duration of ruptured membranes, and year of delivery. CONCLUSIONS: After an active-phase arrest, cesarean delivery increased when there was suspected cephalopelvic disproportion. In addition, we observed a strong correlation between cesarean delivery and the year of delivery, which suggests a change in physician behavior over time, independent of all other risk factors for cesarean. PMID- 8469469 TI - Cognitive deficits in women after childbirth. AB - OBJECTIVE: To test the cognitive function of parturients in the days immediately after delivery. METHODS: One hundred postpartum mothers who delivered normal full term infants were tested on standardized neuropsychological tests--the Wechsler Logical Memory Test and the Wechsler Visual Reproduction Test. Their test results were compared with those of nonpregnant childless women, third-trimester high risk pregnant women, and fathers of newborns. RESULTS: Postpartum women scored significantly lower than nonpregnant women on both tests on the first postpartum day. The use of intrapartum analgesia mitigated the cognitive deficit. High-risk pregnant women and fathers scored lower than nonpregnant women only on the Logical Memory Test. CONCLUSION: Objective documentation that postpartum women have transient deficits in cognitive function, particularly in memory function, can guide caretakers in the design of care plans for the postpartum lying-in period. PMID- 8469470 TI - Differences in postpartum weight retention between black and white mothers. AB - OBJECTIVE: To determine whether the overall retention of weight gained during pregnancy and the factors affecting postpartum weight retention differ by race. METHODS: Data from the 1988 National Maternal and Infant Health Survey were analyzed to examine postpartum weight retention of 20 lb or more among 990 black and 1129 white women who began pregnancy with normal weight for height. The impact of various maternal characteristics on both weight retention and the association between weight retention and race was tested by multivariate methods. RESULTS: Black mothers were twice as likely to retain at least 20 lb than white mothers (adjusted odds ratio 2.20, 95% confidence interval 1.50-3.22). This black white difference did not differ substantially by socioeconomic status. However, many factors affecting postpartum weight retention differed by maternal race. For example, whereas unmarried status was associated with weight retention among white mothers, high parity was associated with weight retention among black mothers. Low socioeconomic status and high prenatal weight gain were associated with an increased risk of weight retention for both black and white mothers. CONCLUSION: These data suggest that population-specific strategies may be needed to help mothers return to their pre-pregnancy weight. PMID- 8469471 TI - Fetal macrosomia and gestational diabetes: what's the problem? AB - OBJECTIVE: To review the definition of, morbidity attendant upon, and interventions designed to prevent fetal macrosomia in gestational diabetes. DATA SOURCES: Both MEDLINE and manual searches of the Index Medicus from 1980-1992 for articles pertaining to fetal macrosomia were employed. Macrosomia was also cross referenced with pregnancy in diabetes. METHODS OF STUDY SELECTION: Seventy-nine articles that provided definitions, data, and opinions relevant to this topic were selected. DATA EXTRACTION AND SYNTHESIS: There is no universally accepted definition of fetal macrosomia. Potential associated morbidities include birth trauma, neonatal hypoglycemia, and childhood and adolescent obesity. Maternal glucose intolerance, age, parity, race and ethnicity, weight, weight gain, smoking status, and fetal gender may influence birth weight. Not all of these factors have been considered in analyses of the impact of interventions designed to prevent macrosomia. CONCLUSIONS: A consensus definition of fetal macrosomia is a necessary and attainable goal. Randomized trials are necessary in which all factors that influence fetal growth and development are uniformly analyzed to develop appropriate clinical interventions. PMID- 8469472 TI - Cost of non-insulin-dependent diabetes in women with a history of gestational diabetes: implications for prevention. AB - Women with gestational diabetes have a 50% risk of developing non-insulin dependent diabetes mellitus within 10 years of delivery and thus constitute a well-defined target population for primary prevention. Current obstetric standards advocate universal screening of all pregnant women for gestational diabetes. Therefore, approximately half the reproductive-age United States population is screened for carbohydrate intolerance before the onset of overt disease. Continuation of dietary and behavioral changes initiated during pregnancy theoretically could delay or prevent progression to overt diabetes. We present an economic model of the health care dollars that could be saved by promoting postpartum life-style changes in women diagnosed with gestational diabetes. Assuming the incidence of diabetes could be reduced by 10, 25, or 50% in a national cohort of women with gestational diabetes, then 32, 140, or 331 million health care dollars could be saved over 10 years. PMID- 8469473 TI - Detection of fetal cocaine exposure by analysis of amniotic fluid. AB - OBJECTIVE: To determine whether analysis of amniotic fluid (AF) using solid-phase extraction and high-performance liquid chromatography is useful in detecting fetal exposure to cocaine and its metabolites. METHODS: Amniotic fluid and urine samples were obtained from 23 subjects with documented cocaine abuse during pregnancy and five subjects without a history of cocaine abuse. Urine samples were also collected from all newborns. Urine samples were screened using conventional immunoassay techniques and confirmed with thin-layer chromatography. Using a modified solid-phase extraction procedure, we removed cocaine and its metabolites from all AF samples and from the newborn urine samples in which the initial screening was positive. Subsequently, we analyzed the extracts with high performance liquid chromatography. RESULTS: Cocaine or benzoylecgonine was detected in 74% of AF samples taken from the 23 known cocaine abusers. In these subjects, conventional maternal and neonatal urine toxicology screens were positive in 61 and 35%, respectively. Concentrations in AF ranged from 400 to greater than 5000 ng/mL for benzoylecgonine and from trace to 250 ng/mL for cocaine. Mean benzoylecgonine recovery from AF was significantly greater than from newborn urine (1800 versus 280 ng/mL, respectively; P < .0001). CONCLUSION: Analysis of AF appears to be useful in detecting gestational cocaine exposure. PMID- 8469474 TI - A new technique of uterine suspension to pectineal ligaments in the management of uterovaginal prolapse. AB - The incidence of uterovaginal prolapse in young women is high in developing countries. Preservation of the uterus is of prime importance in the surgical management of these patients. A new technique of uterine suspension to the pectineal ligaments is presented as an alternative to traditional procedures. Through a Cherney incision, the uterus is suspended to the pectineal ligaments on both sides with mersilene tape. A simultaneous Burch colposuspension can be useful in selected cases. The operation has been done in 20 women, who averaged 27.5 years of age. There was no early or late morbidity during the follow-up period of 6-30 months. Of nine women desiring further childbearing, seven conceived within 6 months of surgery and thus far five have had an uneventful vaginal delivery at term; the other two have continuing normal gestations. There was no recurrence of prolapse at 6 weeks postpartum in any of the women. PMID- 8469475 TI - Diagnosis of pelvic inflammatory disease with 99mtechnetium hexamethylpropylenamine-oxime-labeled autologous leukocytes and pelvic radionuclide scintigraphy. AB - In a prospective study, we assessed the performance of pelvic radionuclide scintigraphy after the injection of 99mtechnetium-hexamethylpropylenamine-oxime labeled autologous leukocytes as a noninvasive tool for the differential diagnosis of pelvic inflammatory disease (PID). The results of radionuclide scintigraphy in 20 women with PID confirmed laparoscopically were compared with the findings in 20 others hospitalized for suspected PID but with PID ruled out later by laparoscopy. The proportion of radionuclide scintigraphic findings demonstrating increased uptake in the genital region, compatible with an inflammatory process, was significantly larger (P < .001) in patients with PID (95%) than in those without PID (15%). The sensitivity of the technique was 95% and specificity was 85%; in all, 90% of the patients were correctly classified. We conclude that radionuclide scintigraphy preceded by the injection of 99mtechnetium-hexamethylpropylenamine-oxime-labeled autologous leukocytes can detect PID in a high proportion of patients. PMID- 8469476 TI - Randomized comparison of laparoscopy-assisted vaginal hysterectomy with standard vaginal hysterectomy in an outpatient setting. PMID- 8469477 TI - Randomized comparison of laparoscopy-assisted vaginal hysterectomy with standard vaginal hysterectomy in an outpatient setting. PMID- 8469478 TI - Myocardial infarction in the third trimester of pregnancy secondary to an aortic valve thrombus. AB - BACKGROUND: Myocardial infarction during pregnancy is rare, at an estimated one case per 10,000 women delivered. The overall mortality rate is 28% and is even higher in the second and third trimesters. We report a myocardial infarction secondary to a thrombus that developed on an artificial aortic valve in a 25-year old woman at 26 weeks' gestation. CASE: The patient, gravida 6, para 3-0-2-3, presented with an acute myocardial infarction despite antepartum anticoagulant therapy with heparin. During her hospitalization, she experienced a second ischemic event, preterm labor, and a small upper gastrointestinal hemorrhage. Nitroglycerin, sublingual nifedipine, and heparin were used to stabilize her cardiac problems, and her uterine contractions were inhibited with tocolytic agents. At 35 weeks' gestation, she underwent an uncomplicated vaginal delivery of a 2608-g viable male infant. CONCLUSION: Pregnancy complicated by myocardial infarction due to a valve thrombosis in the third trimester can be managed with careful attention to controlling the cardiac symptoms and preventing premature delivery. PMID- 8469479 TI - Fixed mini-dose warfarin for prophylaxis of thromboembolic disease in pregnancy: a safe alternative for the fetus? AB - BACKGROUND: Fixed mini-dose warfarin has been used for thromboprophylaxis in high risk nonpregnant patients with encouraging results. The usefulness of this strategy in pregnant women requires documentation of fetal safety. CASE: A woman with antithrombin III deficiency suffered a venous thrombosis during early pregnancy and could not be successfully managed long term with heparin. One milligram of warfarin daily was used for prophylaxis, and serial fetal blood samples were used to monitor the fetal coagulation status. No apparent coagulation abnormalities were demonstrated in the fetus at 33, 36, and 38 weeks' gestation. The woman suffered no further thromboses throughout the remainder of her pregnancy and puerperium. CONCLUSIONS: The efficacy of fixed mini-dose warfarin for prophylaxis in pregnancies at risk for thromboembolic disease will require further investigation. This fetus did not appear vulnerable to coagulation abnormalities as a consequence of the warfarin regimen. PMID- 8469480 TI - Pregnancy complicated by Gorham disease. AB - BACKGROUND: A pregnancy with Gorham disease (massive osteolysis syndrome) is described. To our knowledge, this is the first reported case of a pregnancy associated with this disease. CASE: A 25-year-old woman was seen for pre conception counseling with the diagnosis of Gorham disease. Before pregnancy, magnetic resonance imaging confirmed a stable disease process. The woman and fetus were followed during pregnancy with ultrasound and consultations. Severe preeclampsia developed at delivery, with a significant thrombocytopenia. We delivered the infant by low forceps, with a good outcome. Subsequently, the mother and child were doing well at 18 months postpartum. CONCLUSION: We briefly review this rare bone disease as it relates to pregnancy and provide information for preconception counseling. PMID- 8469481 TI - Acanthosis nigricans and hyperandrogenism in a pregnancy complicated by diabetes. AB - BACKGROUND: Acanthosis nigricans and hyperandrogenism have been associated with diabetes mellitus accompanied by insulin resistance. However, these manifestations have rarely been reported to occur as a result of the insulin resistance of pregnancy. CASE: A 31-year-old woman with diabetes mellitus exhibited severe insulin resistance during pregnancy. At 32 weeks, daily administration of 500 U insulin was required to maintain glycemic control. Skin lesions typical of acanthosis nigricans appeared, and free testosterone levels were elevated (10.3 pg/mL). These manifestations resolved after delivery. CONCLUSION: This case may demonstrate a correlation between reversible gestational insulin resistance and acanthosis nigricans. PMID- 8469482 TI - Symptomatic liver hemangioma with intra-tumor hemorrhage treated by angiography and embolization during pregnancy. AB - BACKGROUND: Cavernous hemangiomas are the most common benign tumors of the liver and are found in about 2% of autopsy patients. The vast majority are small (less than 4 cm) and asymptomatic, but there have been a few reported cases of these lesions leading to severe pain and even spontaneous fatal hemorrhage. Estrogen may cause the growth of liver hemangiomas, but there is a paucity of information concerning the effect of pregnancy upon these lesions. CASE: A patient presented at 18 weeks' gestation with the acute onset of vomiting and epigastric pain. A right upper-quadrant ultrasound scan found a 9-cm hypodense lesion within the liver, and magnetic resonance imaging (MRI) suggested a hemangioma. The lesion was believed to be inoperable, and selective catheterization of the common hepatic artery was performed. An angiogram demonstrated a round vascular mass 12 cm in diameter occupying much of the left side of the liver, with the vascular supply from the middle hepatic artery and to a lesser extent from the left hepatic artery. Embolization was performed, and a post-embolization image demonstrated satisfactory occlusion of the vessels treated. The patient's epigastric pain resolved after the procedure. The lesion was observed with monthly ultrasound and regressed to about 50% of its original size. The patient was scheduled for an elective primary cesarean delivery at 39 weeks to avoid possible rupture of the hepatic hemangioma during the second stage of labor. Her cesarean and postpartum course were uncomplicated. CONCLUSION: A symptomatic liver hemangioma with intratumor hemorrhage can be successfully treated with embolization during pregnancy. Because of the paucity of reported cases, it is uncertain whether vaginal birth is contraindicated in these patients. PMID- 8469483 TI - Intestinal malrotation during pregnancy. AB - BACKGROUND: Malrotation of the intestine is an uncommon anomaly most often seen in infants, but occasionally in adults. Rarely, symptoms from malrotation may occur during pregnancy. CASE: A 30-year-old woman, with a long history of abdominal pain and constipation, developed more frequent and severe symptoms in the second trimester of pregnancy. She was monitored closely and treated conservatively and went on to deliver a full-term, healthy infant. In the postpartum period, barium radiographs demonstrated a midgut malrotation. During exploratory laparotomy, obstructive peritoneal bands were noted and were transected. The mobile cecum and ascending colon were fixated to the abdominal wall. CONCLUSION: Symptoms from a malrotation may develop during pregnancy and may be nonspecific and vague. Although complications from malrotation can be life threatening, a conservative approach with surgical intervention in the postpartum period may be appropriate in the proper clinical setting. PMID- 8469484 TI - Acute fatty liver of pregnancy in a patient with chronic active hepatitis and associated hepatocyte alpha 1-antitrypsin inclusions. AB - BACKGROUND: Acute fatty liver of pregnancy is a rare, potentially fatal condition that shares many of the signs and symptoms of severe preeclampsia. Early reports of this condition noted alarmingly high fetal and maternal mortality rates. However, recent reports have described more favorable outcomes due to prompt recognition and aggressive treatment. We here describe a patient with acute fatty liver of pregnancy superimposed on chronic active hepatitis. CASE: A 27-year-old woman, para 0-1-2-1, presented at 36 weeks' gestation with a 2-week history of malaise, nausea, emesis, diarrhea, and an 18-lb weight loss. The serum concentrations of transaminase enzymes, bilirubin, and alkaline phosphatase were increased, and a mild coagulopathy was present. The patient underwent repeat cesarean delivery and intraoperative needle biopsy of the liver. Histologic examination of the biopsy demonstrated the characteristic changes of acute fatty liver of pregnancy and chronic active hepatitis with associated alpha 1 antitrypsin hepatocyte inclusions. The serum alpha 1-antitrypsin level was mildly elevated and the phenotype was normal (PiMM), excluding alpha 1-antitrypsin deficiency. Viral and autoimmune etiologies for chronic hepatitis were excluded by laboratory studies. The woman experienced rapid resolution of symptoms and laboratory abnormalities in the immediate postoperative period. CONCLUSION: Acute fatty liver of pregnancy may occur in patients with underlying chronic liver disease. Prompt delivery is necessary to reduce the risk of fetal and maternal mortality. PMID- 8469485 TI - Reversible hypertension in pregnancy caused by obstructive uropathy. AB - BACKGROUND: Hypertension with deterioration of renal function after mid-pregnancy often signifies preeclampsia and the need for delivery. CASES: We have encountered three women with reversible hypertension related to obstructive uropathy. The women presented between 21-30 weeks' gestation with hypertension accompanied by significantly increased serum creatinine. Although pregnancy induced hypertension was considered initially in all, there was no other evidence of preeclampsia. In all three, ureteral obstruction was confirmed radiographically and found to be associated with uterine overdistention or congenital urinary anomalies. Relief of obstruction by ureteral stent placement or percutaneous nephrostomy was followed by diuresis and resolution of hypertension. In all three women, pregnancy was extended by more than 6 weeks. CONCLUSION: Urinary obstruction is a rare but potentially reversible cause of hypertension in pregnancy. Relief of obstruction may lead to normalization of blood pressure and negate the need for immediate delivery. PMID- 8469486 TI - Cavernous hemangioma of the uterus in a pregnant woman. AB - BACKGROUND: Cavernous hemangioma of the uterus is a rare but serious condition, especially during pregnancy. Most reported cases ended with hysterectomy in an attempt to control profuse bleeding, and only one of four resulted in a live birth. We describe the sonographic differential diagnosis of this condition and propose management of these patients. CASE: Cavernous hemangioma of the uterus was diagnosed sonographically at 33 weeks' gestation. Conservative management resulted in a favorable outcome for both mother and child. CONCLUSION: Ultrasound is helpful in the prenatal diagnosis of cavernous hemangioma of the uterus; however, other uterine or placental abnormalities with similar sonographic appearances should be considered in the differential diagnosis. PMID- 8469487 TI - Third-trimester uterine rupture following hysteroscopic uterine perforation. AB - BACKGROUND: As operative hysteroscopy becomes more common, long-term complications become apparent. CASE: A 29-year-old woman had a hysteroscopic uterine septum resection. This was complicated by a small fundal puncture. In the ensuing pregnancy, uterine rupture occurred at 33 weeks and resulted in neonatal mortality and maternal morbidity. CONCLUSION: Uterine rupture may follow uterine perforation at operative hysteroscopy; patients contemplating pregnancy after such perforation warrant appropriate counseling. PMID- 8469488 TI - Conservative surgical management of placental implantation site hemorrhage. AB - BACKGROUND: Our purpose is to show that a simple, conservative, fertility preserving surgical technique can be used to control postpartum hemorrhage from a hypotonic placental implantation site. CASE: Postpartum hemorrhage from a hypotonic placental implantation site at cesarean delivery was treated with surgical excision of the hypotonic segment, resulting in immediate cessation of the bleeding when other measures had failed. The patient's postoperative course was uneventful. The uterus and adjacent vascular structures were evaluated with magnetic resonance imaging studies at 4 weeks postpartum and were free of abnormality. CONCLUSION: Simple excision of a hypotonic bleeding site may be desirable and practical when fertility preservation is desired. PMID- 8469489 TI - Use of the peripherally inserted central catheter for parenteral nutrition during pregnancy. AB - BACKGROUND: Parenteral nutrition is required during pregnancy to treat hyperemesis gravidarum and other conditions in which enteral intake is inadequate. We describe the peripherally inserted central catheter. The catheter is inserted into the antecubital vein using local analgesia, thus eliminating some of the risks associated with obtaining central venous access. CASE: Three pregnant patients required parenteral nutrition for refractory hyperemesis gravidarum. The peripherally inserted central catheter was successfully placed, and central venous administration of hyperosmolar solutions was accomplished without complication for periods of 28-137 days. Maternal weight gain and fetal growth were adequate. CONCLUSIONS: The peripherally inserted central catheter avoids some of the risks related to obtaining central venous access and permits long-term administration of parenteral nutrition into the central venous circulation. PMID- 8469490 TI - Successful delivery after age 50: a report of two cases as a result of oocyte donation. AB - BACKGROUND: Because of donor oocyte programs, women who previously were considered too old to successfully achieve conception and delivery can now bear children. To our knowledge, there have been no previous reports of pregnancy outcome in women over age 50 who conceived using donor oocytes. This study presents the pregnancy and delivery data on two women who delivered at age 52. CASES: Case 1 was a 51-year-old woman, gravida 3, para 3, whose three children had been conceived with her first husband more than 20 years previously. She had remarried 18 years before presentation and had been actively trying to conceive for the last 7 years. She was diagnosed as being in menopause based on elevated gonadotropins, amenorrhea, and failure to have progesterone-withdrawal menses. She conceived on her first embryo transfer cycle with embryos derived from donor oocytes and fertilized by her husband's sperm (oocytes were donated by a woman who was undergoing retrieval for in vitro fertilization). During pregnancy she remained healthy, but had uterine prolapse at 20 weeks. She delivered a normal healthy male at 40.5 weeks; cesarean was performed because of a presumptive diagnosis of fetal distress after 3 hours of labor, when monitoring revealed fetal heart decelerations. Case 2 was also a 51-year-old woman, gravida 6, para 4, who wished to conceive with her second husband's sperm through the donor oocyte program. She had amenorrhea of 2 years' duration and elevated gonadotropins. Conception occurred after fertilization of a donor oocyte by her husband's sperm. She had an uneventful pregnancy, but labor was induced at 38 weeks' gestation given the supposed high-risk status of this age group. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. CONCLUSION: Theoretically, the risks of pregnancy complications in older patients are magnified given the aging maternal cardiovascular system, which may predispose these women to placental insufficiency. These first two cases of donor oocyte pregnancies in women over age 50 found no maternal or fetal age-related complications. We hope these reports will encourage all researchers to share their findings so that prospective patients can make better, more informed decisions as to whether they want to participate in donor oocyte programs. PMID- 8469491 TI - Diagnosis and successful treatment of fetal goitrous hyperthyroidism caused by maternal Graves disease. AB - BACKGROUND: Intrauterine diagnosis and treatment of fetal goitrous hyperthyroidism due to maternal Graves disease has not been reported. CASE: A case of fetal goitrous hyperthyroidism caused by maternal Graves disease was diagnosed and treated in the second trimester. High concentrations of both thyroid-stimulatory immunoglobulins (Igs) and thyrotropin-binding inhibitory Igs were detected in both maternal and fetal umbilical venous blood. Maternal propylthiouracil (PTU) treatment resulted in normalization of fetal thyroid function and a decrease in the size of the fetal thyroid goiter. Although euthyroid immediately after birth, the infant later became hyperthyroid and required treatment with PTU. CONCLUSION: The relatively high frequency of fetal thyroid disorders in maternal Graves disease warrants complete maternal and fetal evaluation. Fetal diagnosis and treatment of either hyperthyroidism or hypothyroidism are feasible and necessary to prevent fetal morbidity and mortality. PMID- 8469492 TI - Prenatal diagnosis of congenital lipoid adrenal hyperplasia. AB - BACKGROUND: There are no published reports of prenatal diagnosis of congenital lipoid adrenal hyperplasia, which is the rarest form of congenital adrenal hyperplasia. CASE: Congenital lipoid adrenal hyperplasia was diagnosed prenatally based on the existence of one affected sibling in the family, the presence of an amniotic fluid cell karyotype of 46,XY, the appearance of normal female genitalia on ultrasonography, relatively low amniotic fluid concentration of 17 alpha hydroxyprogesterone, low maternal plasma and urinary concentrations of estriol, and a positive response to the dehydroepiandrosterone sulfate loading test. CONCLUSION: Congenital lipoid adrenal hyperplasia can be diagnosed prenatally. Treatment in early infancy can lead to normal mental and physical development. PMID- 8469493 TI - Congenital ichthyosis with restrictive dermopathy and Gaucher disease: a new syndrome with associated prenatal diagnostic and pathology findings. AB - BACKGROUND: Since 1988, three nonrelated fatal cases of congenital ichthyosis associated with Gaucher disease have been described in Australia. CASE: We present a case of Gaucher disease with congenital ichthyosis and restrictive dermopathy and describe the associated prenatal sonographic findings and pathology of this new syndrome. CONCLUSION: The unusual association of congenital ichthyosis with lipid storage disease may be suspected prenatally. A high index of suspicion may prove this condition to be more common than previously thought. PMID- 8469494 TI - Prenatal diagnosis and obstetric management of Larsen syndrome. AB - BACKGROUND: Larsen syndrome is a disease of generalized defect in collagen formation including multiple disorders of the joints and cardiac anomalies. A review of the literature revealed no previous reported cases in pregnancy. CASE: A 29-year-old woman with known Larsen syndrome thought to be of the autosomal recessive type presented in pregnancy; second-trimester ultrasound suggested fetal involvement with Larsen syndrome. The patient was followed with serial ultrasounds, and she had pediatric and anesthesiologic consultations. She was delivered by cesarean of a female infant whose neck was immediately stabilized. The infant was then taken to the neonatal intensive care unit, where a diagnosis of Larsen syndrome was confirmed. CONCLUSIONS: Larsen syndrome, which may be diagnosed prenatally, is a rare and unique condition that requires multidisciplinary care. Obstetric management must take into account the increased anesthetic and surgical risks to the mother and the risk of fetal injury including cervical spine instability. The genetics of Larsen syndrome are also discussed. PMID- 8469495 TI - Antenatal sonographic findings associated with unilateral pulmonary agenesis. AB - BACKGROUND: Unilateral pulmonary agenesis is a rare anomaly that has a relatively frequent association with other congenital malformations. Prognosis depends in part upon associated anomalies and whether the right or left lung is involved. The prenatal sonographic findings of this defect share some similarities with those of other intrathoracic lesions or congenital diaphragmatic hernia. CASE: Our patient had a twin gestation complicated by early discordant growth and hydramnios. The smaller fetus had cardiac dextroposition, abnormally echogenic left lung tissue, and a flattened but clearly visible left hemidiaphragm. No abdominal viscera were seen in the thoracic cavity. Postnatally, this infant was found to have agenesis of the right lung, a tracheoesophageal fistula, and pyloric stenosis. CONCLUSION: The diagnosis of unilateral pulmonary agenesis should be considered in a fetus with the sonographic findings of a shift of the mediastinal structures, echogenic lungs, and an intact diaphragm. PMID- 8469496 TI - Color flow mapping and Doppler velocimetry in the diagnosis and management of a placental chorioangioma associated with nonimmune fetal hydrops. AB - BACKGROUND: Placental chorioangiomas are the most common tumors of the placenta, occurring in 1% of all pregnancies. With the increasing use of ultrasound, prenatal recognition of these tumors is becoming more common. CASE: A 36-year-old woman presented at 28 weeks' gestation with an intrauterine mass suggested by color flow and Doppler studies to be a vascular tumor. Because of the association of these findings to nonimmune fetal hydrops, management included umbilical blood sampling and intravascular transfusion for fetal anemia. This intervention temporarily corrected the hydrops and significantly prolonged the pregnancy. CONCLUSION: Color flow mapping and Doppler flow studies of intrauterine tumors associated with fetal nonimmune hydrops can be helpful in both diagnosis and management. PMID- 8469497 TI - Metastatic placental lymphoma associated with maternal human immunodeficiency virus infection. AB - BACKGROUND: Pregnancy complicated by maternal human immunodeficiency virus (HIV) infection is increasing in frequency. This report describes a maternal malignancy associated with HIV infection that may complicate pregnancy. CASE: A 33-year-old primigravida was delivered by cesarean. Histologic examination of the placenta revealed the presence of metastatic non-Hodgkin lymphoma of B-cell origin. The patient was then found to be infected with HIV. Nine months postpartum, she was diagnosed with immunoblastic lymphoma. She is currently undergoing chemotherapy. CONCLUSION: Non-Hodgkin lymphoma of B-cell origin is an indication of AIDS. Pregnancies associated with maternal HIV infection may be complicated by this malignancy, which may metastasize to the products of conception. Careful examination of the placenta can detect metastases in women with non-Hodgkin B cell lymphoma. PMID- 8469498 TI - Pregnancy complicated by medulloblastoma with metastases to the placenta. AB - BACKGROUND: Maternal malignancy may complicate as many as one in 1000 pregnancies. Rarely, the tumor may metastasize to the products of conception. We here describe a case of medulloblastoma metastatic to the placenta. CASE: A 21 year-old woman who had previously undergone resection of a posterior fossa medulloblastoma was admitted at 20 weeks' gestation complaining of low back pain. Investigation revealed medulloblastoma metastatic to the bone marrow. The pregnancy was prolonged to 29 weeks' gestation, at which time she was delivered by cesarean. The postoperative course was complicated by coagulopathy, massive bleeding, and pneumonia leading to death. Autopsy showed medulloblastoma metastatic to the bone marrow and placenta. CONCLUSION: Primary intracranial neoplasms may metastasize to the products of conception. The dramatic course of the disease in this patient may suggest that medulloblastoma is responsive to hormonal therapy. PMID- 8469499 TI - Vulvar vestibulitis and interstitial cystitis: a disorder of urogenital sinus derived epithelium? AB - BACKGROUND: Vulvar vestibulitis and interstitial cystitis are enigmatic and controversial conditions. They are increasingly recognized as important causes of genitourinary pain in young women. This report proposes an etiologic association between the two conditions. CASES: We report three patients with both vulvar vestibulitis and interstitial cystitis. Although an association between these conditions has previously been proposed, these are the first case reports of the coexistence of these conditions in the same patient. CONCLUSION: Because both the vestibule of the vulva and the bladder are derived from the urogenital sinus, we propose that the coexistence of vulvar vestibulitis and interstitial cystitis in some patients represents a generalized disorder of urogenital sinus-derived epithelium. PMID- 8469500 TI - Nonfluorescent erythrasma of the vulva. AB - BACKGROUND: Erythrasma is an uncommon vulvar infection, best diagnosed by its fluorescence under the Wood lamp. This report shows that despite a negative Wood lamp examination, the diagnosis can be made histologically. CASE: A 42-year-old woman was referred to our clinic with a persistent candidal infection. Evaluation included a Wood lamp examination, wet mount, and potassium hydroxide test of the affected skin, all of which were negative. A biopsy of the area demonstrated rods and filamentous organisms in the keratotic layer consistent with a Corynebacterium minutissimum infection. The patient was diagnosed as having erythrasma, and she responded to oral erythromycin. CONCLUSION: Persistent vulvar diseases may be caused by erythrasma despite a negative Wood lamp examination. The diagnosis can be made by biopsy of the lesion. PMID- 8469501 TI - Vaginal telangiectasias: unusual presentation of the Osler-Weber-Rendu syndrome. AB - BACKGROUND: The Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia) is an autosomal dominant disorder of blood vessels associated with mucocutaneous telangiectasis and arteriovenous malformations of internal organs. CASE: A 23-year-old woman was found on routine gynecologic examination to have asymptomatic vaginal telangiectasias, a previously unreported initial site of involvement in this syndrome. CONCLUSION: The finding of asymptomatic vaginal telangiectasias on routine pelvic examination should alert the clinician to the possibility of the Osler-Weber-Rendu syndrome. PMID- 8469502 TI - Cryptococcal infection of the vagina. AB - BACKGROUND: Cryptococcal infection is opportunistic and occurs most commonly in immunocompromised patients. Meningitis is the most frequent manifestation and causes marked morbidity and mortality. Other sites are less common. We report a case of vaginal cryptococcal infection. CASE: A 72-year-old patient who had undergone resection of the colon for cancer 9 years earlier was noted to have a suspicious lesion on the right vaginal wall after an abnormal Papanicolaou test. Biopsy of the lesion showed findings compatible with cryptococcal infection. Serial examinations revealed no evidence of systemic infection or immunocompromised condition. Empirical treatment was tried with fluconazole. Follow-up colposcopy showed almost complete disappearance of the vaginal lesion, and histologic section and culture of the tissue failed to reveal cryptococcus. CONCLUSION: Cryptococcal infection is rare, especially in a patient with no evidence of an immunocompromised condition. The preliminary result of fluconazole treatment was satisfactory. However, further follow-up and evaluation are needed to confirm the effectiveness of fluconazole in our patient. PMID- 8469503 TI - Topical sucralfate in the treatment of vaginal ulceration. AB - BACKGROUND: Non-neoplastic vaginal ulceration is at times recalcitrant to traditional methods of treatment. Sucralfate, a basic aluminum salt of sucrose octasulfate, binds preferentially to ulcerated areas and promotes healing, an effect that does not appear to be acid-dependent. CASE: Three cases of vaginal ulceration were treated with vaginal douches of sucralfate 10% suspension twice daily. One of the cases was due to laser ablation for intraepithelial neoplasia, one was of uncertain etiology, and one was caused by pessary use. CONCLUSION: After failure of the initial therapeutic regimens, sucralfate treatment was successful in all three cases and was well tolerated without side effects. Sucralfate vaginal douches should be considered for the treatment of non neoplastic vaginal ulcerations, particularly when other therapy has failed. PMID- 8469504 TI - Neovaginal reconstruction with a rectus abdominis myocutaneous flap. AB - BACKGROUND: Neovaginal reconstruction after pelvic exenteration has several advantages. Besides the obvious psychosocial benefit to the patient and her partner, the incorporation of viable tissue into the pelvic cavity decreases the incidence of infection and small-bowel complications. Several surgical techniques are available to the gynecologic oncologist for construction of a functional vagina. Recently, myocutaneous flaps incorporating the rectus abdominis and gracilis muscles have been used. Disadvantages of the gracilis myocutaneous flap are the 10-20% incidence of flap loss due to vascular compromise and the potential for prolapse. The rectus abdominis myocutaneous flap is a large flap with a reliable blood supply that allows mobilization without tension on the vascular pedicle, resulting in a much lower incidence of vascular compromise. CASE: We present two case reports, a review of the gynecologic and surgical literature, and the techniques for vaginal reconstruction using the rectus muscle as a myocutaneous flap. CONCLUSIONS: The outcome for both patients was a satisfactory functional vagina that was technically easy to construct. The rectus abdominis myocutaneous flap can provide an adequate neovagina with minimal morbidity. PMID- 8469505 TI - Salpingitis or oophoritis: what causes fever following oocyte aspiration and embryo transfer? AB - BACKGROUND: Febrile morbidity following in vitro fertilization and embryo transfer (IVF-ET) is a rare but possibly serious complication. This report describes a case of salpingitis after IVF-ET and discusses the possible reasons for febrile morbidity following this common procedure. CASE: A 37-year-old woman undergoing IVF-ET for tubal factor infertility developed sudden, severe pelvic pain, fever, and leukocytosis 24 hours after ET. Laparoscopy revealed bilateral suppurative pyosalpinges with cystic, hemorrhagic ovaries. Pain, fever, and leukocytosis resolved with conservative surgery and intravenous antibiotic therapy. CONCLUSIONS: This case presents laparoscopic documentation of a rare complication of oocyte aspiration and/or ET, namely, salpingitis. Possibilities for the development of salpingitis following IVF-ET include activation of quiescent bacteria within the fallopian tubes from a previous pelvic infection, puncture of the bowel during oocyte aspiration, inoculation of the pelvis with cervicovaginal flora during oocyte aspiration, and introduction of bacteria-laden secretions or air into the fallopian tubes during ET. Although rare, the possibility of severe pelvic infection following IVF-ET warrants consideration of prophylactic antibiotic coverage. PMID- 8469506 TI - Tubal pregnancy associated with ampullary tubal leiomyoma. AB - BACKGROUND: Fewer than 100 cases of leiomyoma of the fallopian tube have been described in the literature; most of them are asymptomatic. CASE: A woman presented with a tubal pregnancy which, at laparotomy, proved to be distal to a leiomyoma of the tube. CONCLUSION: Tubal myomas may predispose to tubal implantation of a conceptus. To our knowledge, this is the first time a tubal leiomyoma and a tubal pregnancy have been reported in the English literature. PMID- 8469507 TI - Laparoscopic segmental bladder resection for endometriosis: a report of two cases. AB - BACKGROUND: The proper treatment of bladder endometriosis is unknown. CASE: Two women with endometriosis involving the full thickness of the bladder wall experienced persistent hematuria during menstruation. They had not responded to previous conservative medical or surgical therapy, so we performed laparoscopic segmental resection, with satisfactory results. CONCLUSION: Hematuria during menstruation due to endometriosis of the bladder is uncommon. In the two cases presented, good results followed laparoscopic segmental resection. PMID- 8469508 TI - Spontaneous vaginal expulsion of Hulka clips. AB - BACKGROUND: Laparoscopic Hulka clip application is a common method of outpatient sterilization in women. We present a patient who experienced spontaneous expulsion of two Hulka clips. CASE: A 21-year-old woman was seen 17 months after sterilization because of spontaneous, asymptomatic passage of two Hulka clips into the vagina. The passage of one clip went unnoticed by the patient. Radiographic studies confirmed the migration and absence of two Hulka clips previously placed on the left fallopian tube. CONCLUSION: In rare circumstances, Hulka clips can migrate from the abdominal cavity and be expelled spontaneously, possibly by transuterine passage. This migration may occur without the patient's knowledge. PMID- 8469509 TI - Familial peripartum cardiomyopathy after molar pregnancy. AB - BACKGROUND: The potential complications of molar pregnancy are numerous and well defined, but associated peripartum cardiomyopathy has not been reported. CASE: A 16-year-old primigravida with a family history of peripartum cardiomyopathy requiring cardiac transplantation underwent suction curettage of a complete mole at 12 weeks' gestation. Three months after evacuation, she developed congestive heart failure. Radionuclide ventriculography demonstrated an ejection fraction of 30%, echocardiography revealed enlargement and ventricular hypokinesis, and a myocardial biopsy specimen contained hypertrophy and fibrosis without necrosis or active inflammation. The patient improved with medical therapy. CONCLUSION: Peripartum cardiomyopathy is a potential complication of molar pregnancy. In spite of the poor prognosis sometimes reported for this disease, good functional outcome may follow. PMID- 8469510 TI - Recurrent pancreatitis associated with in vitro fertilization. AB - BACKGROUND: We report the possible association between in vitro fertilization (IVF) and recurrent acute pancreatitis. CASE: A patient developed acute pancreatitis during each of two cycles of IVF. On a spontaneous cycle, serum triglycerides were as follows: early follicular phase 2.34 mmol/L, mid-follicular phase 4.17 mmol/L, and late follicular phase 6.6 mmol/L. During an episode of acute pancreatitis, the serum triglyceride level was 38.45 mmol/L. CONCLUSION: Acute pancreatitis may occur in patients with a family or personal history of hypertriglyceridemia who are candidates for IVF. PMID- 8469511 TI - Endodermal sinus tumor of the vagina: radiation therapy and progeny. AB - BACKGROUND: Extraovarian endodermal sinus tumor generally originates in the vagina or cervix of young girls. Some 50 cases are known, all younger than 3 years of age. Many were treated with outdated regimens, and there are 5-year survival data on only nine of them. We describe a curative outcome of primary radiation only. CASE: A 40-year-old woman had a history of localized endodermal sinus tumor of the vagina, stage I, treated by brachytherapy at the age of 6 months. Radiation had a severe impact upon the later functioning of her pelvic organs, with marked deformity of the pelvic floor, vagina, urethra, and bones of the pelvic outlet. She conceived by homologous insemination at the age of 34. Delivery was by cesarean at 31.5 weeks' gestation. CONCLUSION: Current forms of management give preference to limited excisional surgery and multi-agent chemotherapy, analogous to that used for the treatment of endodermal sinus tumor of the ovary. This is the first report of a patient treated by radium needles and the only known patient who had a subsequent pregnancy. PMID- 8469512 TI - Development of vaginal adenosis following combined 5-fluorouracil and carbon dioxide laser treatments for diffuse vaginal condylomatosis. AB - BACKGROUND: The management of vaginal human papillomavirus (HPV) lesions may be difficult. We report an unusual long-term consequence of treatment. CASE: A 40 year-old woman presented with vaginal adenosis following treatment of multiple vaginal condylomata by endovaginal applications of 5% 5-fluorouracil cream and vaporization of the remaining subclinical condylomata by CO2 laser. CONCLUSION: The approach to the management of vaginal condylomatosis should take into consideration the possible later occurrence of adenosis. PMID- 8469513 TI - Agency for health care policy and research: clinical practice guidelines endorsed by ANA. PMID- 8469514 TI - AHCPR guideline: pain management. PMID- 8469515 TI - HIV client education--what is your role? PMID- 8469516 TI - Karen's delivery--graceful and natural. PMID- 8469517 TI - Lipid droplet accumulation in the exocrine glands of the newborn rat. AB - Exocrine glands including the submandibular gland, sublingual gland, exocrine pancreas and exorbital lacrimal gland of newborn rats aged 0 to 14 days were examined morphologically, and the following results on the accumulation of lipid droplets were obtained. Lipid droplets tended to localize in secretory cells, especially in their basal cytoplasm. The degree of lipid droplet accumulation varied with the type of exocrine gland. There were large accumulations in the sublingual gland, submandibular gland, and exocrine pancreas, but accumulations were small in the exorbital lacrimal gland. No difference in lipid droplet accumulation was recognized between the 2 types of secretory cells in the sublingual gland. The accumulation of lipid droplets peaked 24-48 hours after birth in the sublingual gland, submandibular gland and exocrine pancreas, but this peak was not clearly observed in the exorbital lacrimal gland. In the group of newborn rats separated from their mothers and therefore not suckled, no lipid droplets were observed in any gland, suggesting a close relationship between lipid droplet accumulation and suckling. PMID- 8469518 TI - Arterial supply of the maxillary teeth in the crab-eating monkey (Macaca fascicularis). AB - Superior dental rami diverging from arterial multi-resources of the crab-eating monkey were investigated by means of plastic corrosion castings. Correlations between the dental ramus/rami entering the apical foramen/foramina of each maxillary tooth were elucidated. Superior dental rami supplying the maxillary teeth diverged from the posterior superior alveolar, infraorbital, descending palatine, major palatine and sphenopalatine arteries as follows: The posterior superior alveolar gave rise to molar branches which supplied three molars and rarely an additional two premolars, to premolar branches and to a canine branch as its terminus. The infraorbital gave off canine branches. The descending palatine gave rise to a molar branch which supplied the lingual root of each molar. The major palatine gave rise to a premolar branch which supplied the lingual roots of two premolars and the 1st molar, and an incisive branch which supplied two incisors. The sphenopalatine supplied the lingual root of each molar and rarely the 1st premolar in addition. Two incisors were supplied by the major palatine (100%), the canine by the posterior superior alveolar (50%), this artery and the infraorbital (43.3%) or the infraorbital only (6.7%). Three roots of each premolar were supplied by the posterior superior alveolar, occasionally the lingual root (16.7%) and mesiobuccal root (3.3%) of the 1st premolar by the major palatine, the lingual root of the 2nd premolar by the major palatine (6.7%) and the sphenopalatine (3.3%). Two buccal roots of each molar were also supplied by the posterior superior alveolar (100%), occasionally the lingual root of the 1st molar by the descending palatine (6.7%), the major palatine (6.7%) or the sphenopalatine (3.3%), the lingual root of the 2nd molar by the descending palatine (30%), the sphenopalatine (10.0%) or the infraorbital (3.3%), the lingual root of the 3rd molar by the descending palatine (23.3%), the sphenopalatine (20.0%) or the infraorbital (3.3%). Superior dental rami diverging from the posterior superior alveolar artery were distributed to the molars, premolars and canine as principal arterial vessels of the crab-eating monkey. The descending palatine, sphenopalatine and the infraorbital arteries were supplementary to the above main arteries. Two incisors were only supplied by the major palatine but the anterior and middle superior alveolar were not observed. PMID- 8469519 TI - Correlative light and electron microscopy of the same sections embedded in HPMA, Quetol 523 and MMA. AB - Semithin sections, cut from tissues stained with acid and basic dyes after embedding in 2-hydroxypropyl methacrylate, Quetol 523 and methyl methacrylate, showed cytoplasmic components at a high resolution by light microscopy. These same sections could then be viewed, after osmium tetroxide, uranyl and lead staining, by the electron microscope. These sections had a number of inherent advantages: they could be observed with a light microscope; they facilitated analysis of cellular structures in the identical sites, and they were frequently the optimum thickness to provide three-dimensional information. We clearly established the structural detail of this same-section correlative light-electron microscopy approach by showing that the coloured materials observed in such sections of cells followed the distribution of fine structures within the same sections as determined by electron microscopy. In some instances the fidelity of the correlation between the distribution of the coloured area and cytoplasmic components in identical cells of the same section revealed significant details which could not visualized in thin sections. This technique, therefore, provided a simple and useful solution to many problems that require the localization of cellular components in identical cells selected previously by light microscopy. PMID- 8469520 TI - On the arterial supply in the human biceps brachii muscle. AB - The distribution of the arterial supply and innervation of skeletal muscle in the whole human body has been being researched in our laboratory. The results obtained on the biceps brachii from 25 bodies (50 sides) are reported here. Generally, in this muscle, A. coracobrachialis (Cb, SATO, 1980), a branch of A. axillaris (Ax), is distributed at the upper muscle bundles of the short head after running parallel to N. musculocutaneus (Nmc) and supplying M. coracobrachialis. The main artery (Ma), which is a branch of A. brachialis (Br), is distributed at the upper and middle parts of both heads, and the point where Ma enters the muscle bundles almost coincides with the point where R. brachialis (Rb) branches from Nmc. R. biceps brachii (Rbi), which is distributed only at this muscle and Om, the common trunk to other muscles, is distributed at the lower part of the muscle bundles. The arterial supply of this muscle was classified as follows according to the conditions of origin and its distribution. Type I: Ax(Cb) was distributed to the upper part of the muscle bundle. Type II: The absence of Ax(Cb) in the upper part of the muscle bundle. Type A, a and 1: Ma.Br(Om) supplying the long, short and both heads of the biceps brachii. Type B, b and 2: Ma.Br(Rbi) supplying the long, short and both heads of the biceps brachii. In the long head, Type II-A accounted for 62.0%, Type II-B for 30.0%. In the short head, Type I-a was 62.0%, Type I-b 28.0%. In both heads, Type I-1 was 62.0%, Type I-2 28.0%. There were significant differences in the distribution of the nutrient arteries between the long and short heads. A. brachialis superficialis (Bs) was recognized in 3 of these cases (2 cases of Type III and 1 case of Type VII by Adachi's classifications), which were rare cases. In these cases, arterial branches other than Cb branching from A. brachialis profunda are branches of Bs. This means, judging from ontogeny, that Bs, the blood vessels in the superficial layer, supplies this muscle, which belongs to the superficial layer of the brachium. PMID- 8469521 TI - Persistent sciatic artery. Case report. AB - A case of a persistent sciatic artery in a 60-year-old Japanese man is reported. The right persistent sciatic artery (5 mm in diameter) was joined to the internal iliac artery proximally and to the popliteal artery distally. The terminal vessel of the femoral artery (3 mm in diameter) was connected to the sciatic artery at the popliteal fossa. PMID- 8469522 TI - Arterial supply in the human pectoralis minor muscle. AB - In the following, we report our findings obtained as a result of injecting an acrylic pigment in the arteries supplying the pectoralis minor muscle in 50 lateral chests of 26 Japanese adults (15 males and 11 females). In the pectoralis minor muscle, the muscular bundle near the terminal is supplied by A. processus coracoideris (Pc, Sato-Takafuji, '85) or A. coracobrachialis (Cb, Sato, '80) of A. axillaris (Ax), while its middle upper and lower peripherals are supplied by A. thoracoacromialis (Ta) and A. partis abdominalis (Pab, Sato, '76), respectively. Further, the upper and lower peripherals at its origin are supplied by A. thoracica suprema (Ts) and A. thoracica lateralis (Tl), respectively. Pc, Cb, Pab and Ts may occasionally be absent. Arteries supplying this muscle are classified according to their origins and routes of distribution, as follows. Type I-a: Pc or Cb, Ta, Pab, Ts and Tl are present, 32%; Type II-a: Ts is absent from Type I-a, 14%; Type III-a: Pb and Pc are absent from Type I-a, 20%; Type IV a: Cb, Pc and Ts are absent from Type I-a, 10%. Type b is Type a without Pab. The rates of appearance of Type I-b, II-b, III-b and IV-b were all 6%. The ratios of distribution in area a were as follows, in order of decreasing ratio: 37.6% for Pab (37 cases), 32.4% for Tl (49 cases), 30.2% for Ta (49 cases), 10.8% for Ts (32 cases), 7% for Cb (9 cases), and 6.37% for Pc. In the pectoralis minor muscle, the major supplying arteries are Pab, Tl and Ta, and where Pab was absent, this was compensated for by a branch of Ta. The total number of supplying arteries in this muscle was two to five, with the majority, or 36%, having four arteries. As for sex differences in the incidence of each type, Type I-a appeared more often in males (40%) than in females (20%). The rates according to the ribs of origin were 46%, 36%, 16%, and 2% for types 2.3.4.5, 3.4.5, 2.3.4, and 2.3.4.5.6, respectively. It was interesting that all Type II and Type IV cases without Ts corresponded to Type 3.4.5 without the muscular bundle arising from the second rib, as it suggests the process of degeneration of the pectoralis minor muscle in Homo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8469523 TI - Immunoelectron microscopic localization of basic FGF in neuroglias and neurons of the trigeminal mesencephalic and motor nuclei. AB - Discrepancies between previous light microscopic studies on the localization of basic fibroblast growth factor (bFGF) in neuroglias and neurons of the normal rat brain prompted us to investigate, by electron microscopy, the subcellular localization of bFGF-like immunoreactivity in neuroglias and neurons of the trigeminal motor and mesencephalic nuclei. Immunostaining intensity differed from astrocyte to astrocyte; in astrocytes labeled heavily with bFGF antiserum, the precise subcellular location of immunoreaction deposits was difficult to determine, whereas mildly labeled astrocytes contained reaction products in subcellular regions apart from gliofilaments, mitochondria and Golgi apparatus. A comparison of immunostained sections with negative control ones at the light and electron microscopic levels revealed that astrocyte nuclei occasionally showed bFGF immunoreactivity. Immunoreactive astrocyte processes were also found in close apposition to blood vessels. bFGF was detected mainly in intracellular structures close to free ribosomes and the endoplasmic reticulum of immunoreactive oligodendrocytes and neurons; microglias rarely showed immunostaining. The nuclei of the cells with bFGF contained immunoreaction deposits of varying intensity, mainly in the euchromatin and rarely in the heterochromatin. Occasionally, bFGF of neuroglial origin accumulated in the vicinity of the interface between neurons and neuroglias. The extracellular matrix was not immunoreactive in any of the areas examined. These findings suggest that certain populations of astrocytes and oligodendrocytes as well as neurons in the normal brain contain bFGF-like substances. PMID- 8469524 TI - Fine structure and elemental analysis of the enamel in the cryptobranchid salamander Megalobatrachus japonicus. AB - Teeth from Megalobatrachus japonicus were prepared for scanning electron microscopy (SEM) and electron microprobe analyzer (EMPA) to assay the elements of the enamel layer. The enamel layer of each of tooth is thin and the arrangement of the enamel crystals is regular in the Megalobatrachus japonicus. Based on calcium, phosphate and magnesium levels of distribution, the calcification level of the enamel layer differs between the labial and lingual surfaces. Concentrations of iron and fluoride are located in both portions of the enamel layer as well. The presence of trace elements and distribution of calcified levels are related to the mineral formation in the enamel layer and function of the teeth during feeding. PMID- 8469525 TI - The regional variation of crypt architecture in the mouse colorectal mucosa with special reference to the process of proliferation. AB - The NaOH cell-maceration method was applied to the mouse colorectal mucosa to demonstrate the three-dimensional architecture of the lamina propria, especially that of the glandular crypts. In the surface of the lamina propria, there existed the longitudinal ridges and furrows. In the ridges, the crypts opened to the lumen individually, and had no internal partitions separating a crypt. The lateral walls of the crypts in the ridges had numerous hemispherical concavities into which the epithelial cells were tightly fitted. In the furrows, on the other hand, the crypts were subdivided into several smaller crypts by the internal partitions, and were termed as the "protocrypts". Considered from these findings, the crypts in the ridges appear to be matured, while the protocrypts in the furrows to the crypts undergoing process of proliferation. Further, it is suggested that the crypts proliferate in the furrows and, then, populate in the ridges as the mature crypts. PMID- 8469526 TI - A case of the human sternocleidomastoid muscle additionally innervated by the hypoglossal nerve. AB - An anomalous nerve supply from the hypoglossal nerve (XII) to the sternocleidomastoid muscle (SM) was observed in the right neck of an 82-year-old Japanese female. This nerve branch arose from the hypoglossal nerve at the origin of the superior root of the ansa cervicalis. The nerve fiber analysis revealed that this branch consisted of fibers from the hypoglossal nerve, the first and the second cervical nerves and had the same component as the superior root of the ansa cervicalis. SM appeared quite normal and the most part was innervated by the accessory nerve and a branch from the cervical plexus. The anomalous branch from XII supplied the small deep area near the anterior margin of the middle of the sternomastoid portion of SM. It is reasonable to think that the small deep area of SM, which was innervated by the anomalous branch from XII, occurs as the result of fusion of the muscular component from infrahyoid muscles. If the muscular component does not fuse with SM, it is thought to appear as an aberrant muscle such as the superior sternoclavicular muscle (Hyrtl) which is also supplied from a branch of the superior root of the ansa cervicalis. PMID- 8469527 TI - Fine structural aspects of the anterior necrotic zone in the leg bud of the chick embryo. AB - A fine structural study was undertaken on the area called the anterior necrotic zone of leg buds of the chick embryo at stages 22-29. Physiologically dying cells, which were distributed in the mesenchymal area, were characterized by increased electron density of the cytoplasm, appearance of electron lucent vacuoles and condensed chromatin pattern. Many of the dying cells seemed to be fragmented into several pieces of cell debris during the necrotic process. Two kinds of cells were observed to take up the necrotic cells; one type, large cells 15 microns or more in size and irregular in shape, which had lysosomes, extended microvillus-like cytoplasmic projections and pseudopods, took up pieces of necrotic cells by phagocytosis and stored them in acid phosphate-negative and positive vacuoles. The other type was several microns in diameter with numerous free ribosomes and stored a small number of vacuoles containing cell debris. At stage 29, profiles of necrotic cells lying free in the mesenchymal area, and cells containing one or two vacuoles filled with cell debris decreased in number as well as large cells containing numerous vacuoles, whose contents seemed to be degraded. When pieces of the anterior portion of chick leg buds at stage 24 were organ-cultured for 3 days after glutaraldehyde-fixed mouse red blood cells were injected, the red blood cells were taken up into cells in the mesenchymal area. Formation of large cells containing numerous vacuoles stuffed with red blood cells was rare. These findings may imply that most necrotic cells in the anterior necrotic zone are disposed of by macrophages and that some are endocytosed by mesenchymal cells. PMID- 8469529 TI - Notes about nursing from Botswana, Africa, Part II. PMID- 8469528 TI - Developmental anatomy of the mouse stapediovestibular and temporomandibular joints. AB - The genesis, development and growth of the mouse stapediovestibular joint (SVJ), which contains the annular ligament, and the temporomandibular joint (TMJ) were examined in an attempt to study the stress-bearing articular tissue that is thought to be derived from embryonic mesenchyme; the findings were also compared with those in the ossicular joints. The following conclusions were obtained: 1) The articular cartilage of the mandibular condylar process, stapedial foot plate and otic capsule is derived from fetal fibrous articular tissue. 2) The fetal TMJ developed into a typical double diarthroses containing an articular disc. 3) The fetal syndesmodial SVJ differentiated into the annular ligament containing characteristic palisade-like fibroblasts and hammock-like fibers; no interzone formation or synovial cavities were observed in the completed and mature syndesmodial SVJ. 4) Like the TMJ, the major elastic system fibers in the annular ligament were also mechanical-resistant elaunin. 5) Elastogenesis was closely related to functional and mechanical factors in the auditory ossicular chain, TMJ and annular ligament; the mature incudomalleal and incudostapedial joints contained mainly mature elastic fibers, but the mature SVJ and immature TMJ contained mainly pre-elastic elaunin fibers. 6) Stress elastosis, turnover of the fibrillar component and age changes in cellular and fibrous components were not evident in either the mature SVJ or the young functional TMJ. PMID- 8469530 TI - New advance directive law. PMID- 8469531 TI - Magnetic resonance imaging or arthrographic diagnosis of internal derangement of the temporomandibular joint. Correlation comparison study with arthroscopic surgical confirmation. AB - Although arthrography has long been considered a gold standard for the diagnosis of internal derangements of the temporomandibular joint, magnetic resonance imaging has rapidly proved to be a valuable tool for other insights into soft tissue structures. The goals of this study were twofold: (1) to compare the diagnostic efficacy of arthrography with magnetic resonance imaging and (2) to compare these results with the actual arthroscopic findings. The correlation between arthroscopic examination and independent fluoroscopic arthrogram and magnetic resonance imaging was high for the diagnosis of anterior disk displacement, as were the correlations between arthroscopic examinations and fluoroscopic arthrograms on diagnosing disk perforations. These findings, together with the apparent specialized abilities of the arthroscopic examination to yield information on the quality of the surface tissues (e.g., cartilage degeneration, synovitis, proliferations) led us to conclude that diagnostic arthroscopy may prove to be as valuable to the maxillofacial surgeon for the diagnosis of intracapsular temporomandibular joint disorders as it is for the orthopedic surgeon in diagnosing other joint disorders. PMID- 8469532 TI - Osteoarthrosis, the temporomandibular joint, and Eagle's syndrome. AB - Temporomandibular joint osteoarthrosis is common but typically asymptomatic. This article describes a patient with symptomatic left temporomandibular joint osteoarthrosis in whom pain in the right side of the tongue and ear, and dysphagia, subsequently developed simulating Eagle's syndrome. The concept of Eagle's syndrome is reviewed. PMID- 8469533 TI - Microscrew and microplate systems for select osteotomies in orthognathic surgery. AB - The use of the semirigid screw and plate systems is common place in orthognathic surgery by many oral and maxillofacial surgeons. The size of the screw and plate systems used is commonly designated as mini or osteotomy size. Screw diameter is generally 2.0 mm and plate thickness range is 0.8 mm to 1.2 mm. The systems available perform very well for the majority of osteotomies. There are circumstances when these mini systems are not appropriate. Recently developed microsystems have been applied by us in selected cases of orthognathic surgery. The smallest of the microsystem screws are 0.8 mm diameter and all are available in 2, 3, 4, 5, 6, 8 mm lengths. Some microplates are 0.3 mm thick and available in various shapes including a straight chain. The resultant profile thickness of screw plus plate system becomes 0.8 mm. PMID- 8469534 TI - Dental extractions in patients with bleeding disorders. The use of fibrin glue. AB - Eighty patients with various bleeding disorders underwent 135 extractions without preventive replacement hematologic therapy. The local hemostatic control involved the use of fibrin glue Beriplast. Secondary bleeding occurred in 9 of 12 patients with severe hemophilia when the concentration of the aprotinin in the fibrin glue was 1,000 KIU/ml. When it was increased to 10,000 KIU/ml and swish and swallow rinses of tranexamic acid before and after the dental extractions were added, only 3 of 25 hemophilia patients suffered from secondary bleeding. Local use of fibrin glue is a safe and cost-effective tool to treat patients with severe bleeding disorders. None of the 43 patients with coagulopathies other than severe hemophilia suffered bleeding after extractions. PMID- 8469535 TI - Analysis of the analgesic efficacy and cost-effective use of long-acting local anesthetics in outpatient third molar surgery. AB - Bupivacaine hydrochloride, an amide-type of long-acting local anesthetic was compared with lidocaine hydrochloride to determine its analgesic efficacy and its cost-effective use in an oral and maxillofacial surgery private practice. The results show that 0.5% bupivacaine hydrochloride provides greater analgesia than 2% lidocaine, with an insignificant cost increase to the operating surgeon. PMID- 8469536 TI - Central giant cell granuloma. Report of a case. AB - The central giant cell granuloma is a tumor that has great potential for the displacement of teeth and the development of a facial deformity. Although its cause and behavior are still matters for discussion, its early diagnosis and treatment are a priority. We describe a patient with a large benign central giant cell granuloma of the anterior mandible. The clinical, radiographic, and histologic appearance, as well as the appropriate treatment, are discussed in light of the current literature. PMID- 8469537 TI - Quincke's disease: nonhereditary angioneurotic edema of the uvula. AB - We report two cases of Quincke's disease, an isolated form of angioneurotic edema involving the uvula that is induced by several factors, including foods, drugs, and inhalants. Although Quincke's disease has prominent oral manifestations, it has only rarely been described in the dental literature. The rapid onset and progression of the disorder, combined with the risk of respiratory compromise, may result in a serious medial emergency. Clinical manifestations include a nonerythematous swollen uvula, fullness in the throat, and signs of airway obstruction. A hereditary form of angioneurotic edema is associated with a biochemical defect; this must be differentiated from nonhereditary, localized forms such as Quincke's disease to determine appropriate treatment and predict prognosis. Clinical features and laboratory tests can distinguish hereditary angioneurotic edema from the nonhereditary form. PMID- 8469538 TI - Direct immunofluorescence of detached gingival epithelium for diagnosis of cicatricial pemphigoid. Report of five cases. AB - The diagnosis of mucosal cicatricial pemphigoid is often problematic because of frequent false negative or equivocal biopsy results. We describe an immunofluorescent technique that uses detached gingival epithelium for diagnostic purposes when oral manifestations of cicatricial pemphigoid are suspected. Erythematous mucosa that is gently rubbed produces detached epithelium that is then submitted for direct immunofluorescence studies along with tissue acquired via conventional techniques. In the five cases reported, the detached gingival epithelium stained intensely for immunoglobulins and complement on the basilar pole of the basal epithelial cells. The donor sites healed without a resultant periodontal defect. This adjunctive biopsy technique offers the advantage of easily procuring gingival tissue with deposition of immunoreactants that are quite specific for the diagnosis of cicatricial pemphigoid. PMID- 8469539 TI - Burning mouth syndrome. Evaluation of multiple variables among 85 patients. AB - The relationship between burning mouth syndrome and 48 variables was investigated in 241 patients, 45 years old and older, who had attended the Oral Medicine Clinic of the Faculty of Dentistry, University of Stellenbosch during a period of 4 years. A total of 85 cases of burning mouth syndrome were diagnosed in 65 women and 20 men. Statistically significant relationships (p < 0.05) were found with self-medication, xerostomia, and other salivary disturbances in both men and women with burning mouth syndrome when compared with their respective controls. Among the women with BMS, significant relationships were also found with anemia, inadequate diet, chronic infection, hormone therapy, ulcerative/erosive lesions, and atrophy. In contrast men with BMS showed statistically significant relationships between taking prescribed medication, central nervous system disturbances, gingivitis, and denture-related problems. In addition, significant associations were related to variables such as psychogenic factors, regurgitation, flatulence, and periodontitis. PMID- 8469540 TI - Psychiatric morbidity in burning mouth syndrome. Psychiatric interview versus depression and anxiety scales. AB - Seventy-four patients with burning mouth syndrome underwent a psychiatric interview; Hamilton's Depression and Anxiety Scales were applied independently. A psychiatric diagnosis was established in 38 cases (51.35%). Depression was the predominant disorder. The evaluation scales showed that when present, anxiety greatly influences the psychiatric condition of these patients. The differences in the results obtained with the two methods are discussed. PMID- 8469541 TI - Effect of radioactive iodine therapy on salivary flow rates and oral Streptococcus mutans prevalence in patients with thyroid cancer. AB - Unstimulated and stimulated salivary flow rates, Streptococcus mutans samples, and dental caries data were obtained from 50 patients with thyroid cancer who had received radioactive iodine, I131, from 0.3 to 20 years earlier. The salivary flow rates were compared with a healthy control group, and the S. mutans counts were compared to a group of patients with head and neck cancer who were sampled before radiotherapy. Flow rates were found to be significantly lower in the patients with thyroid cancer, and S. mutans levels were slightly but not significantly higher than the controls. Longitudinal flow rate data taken on four patients, who served as their own controls before and after I131 therapy, indicated a trend in saliva reduction. PMID- 8469542 TI - Salivary and lacrimal gland involvement in a patient who had undergone a thyroidectomy and was treated with radioiodine for thyroid cancer. AB - A patient with bilateral, insidiously developing enlargement of the parotid glands that started 1 year after a total thyroidectomy and ablative radioiodine therapy (200 mCi I131) for papillary carcinoma is presented. The patient displayed prolonged periods of hypothyroidism accompanied by hypercholesterolinemia, notwithstanding hormone replacement therapy. Three years after surgery, parotid and lacrimal gland functions were reduced and fatty degeneration of the parotid parenchyma was demonstrated histologically. The submandibular and sublingual glands were preserved. It is suggested that the hormonal and metabolic derangements are responsible for the glandular dysfunction, rather than a direct effect of iodine on the glands. PMID- 8469543 TI - Morphologic and growth effects of tobacco-associated chemical carcinogens and smokeless tobacco extracts on human oral epithelial cells in culture. AB - Epidemiologic studies show an increase in the use of smokeless tobacco but few in vitro studies have directly assessed the potential for smokeless tobacco-induced oral carcinogenesis. Oral keratinocytes were grown to 90% confluence from explants of human labial and gingival mucosa at 34 degrees C, 5% CO2 in defined media. Epithelial monolayers were subsequently subcultured and then treated for 1 hour with aqueous extracts of moist or leaf smokeless tobacco, or with 0.25 to 1.0 ng/ml of three common smokeless tobacco carcinogens: 4-(N-methyl-N nitrosamino)-1-(3-pyridinyl)-1-butanone; N-nitrosonornicotine; and benzo(a)pyrene. Even though the controls and most treatment groups terminally differentiated, cells exposed to 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1 butanone, N-nitrosonornicotine, and moist and dry extract continued to divide, maintained a differentiated phenotype for 8 1/2 to 10 weeks in culture, and displayed focal growth and morphologic changes suggestive of early stages in cell transformation. PMID- 8469544 TI - Multiple idiopathic mandibular bone cysts in a patient with osteogenesis imperfecta. AB - Although the most common oral manifestation of osteogenesis imperfecta is dentinogenesis imperfecta, several authors have described jaw fractures and radiolucent bone lesions associated with this disease. We report a case of a 23 year-old white woman with osteogenesis imperfecta and dentinogenesis imperfecta who developed multiple unilocular, bilateral, radiolucent lesions of the mandible 5 years after presenting with a condylar fracture. This is the first documentation by surgical and histopathologic examination that the radiolucent lesions in this particular case represent multiple idiopathic bone cysts. PMID- 8469545 TI - A case of neurocristopathy that manifests facial clefting and maxillary duplication. AB - A case of a 6-year-old child with three facial clefts and maxillary duplication is presented. Computerized three-dimensional reconstruction from computerized tomography imaging was used in the diagnosis of this patient, and an explanation of the possible embryologic causes of this malformation is discussed. PMID- 8469546 TI - Intraoral sebaceous hyperplasia. Diagnostic criteria. AB - Surprisingly little is understood about the physiologic and pathologic processes that involve intraoral sebaceous glands. Neoplasms are rare. Hyperplasia of these glands is undoubtedly more common, but criteria for the diagnosis of intraoral sebaceous hyperplasia have not been established. These lesions are too often misdiagnosed as large "Fordyce granules" or, when very large, as sebaceous adenomas. On the basis of a series of 31 nonneoplastic sebaceous lesions and on published data, the following definition is proposed: intraoral sebaceous hyperplasia occurs when a lesion, judged clinically to be a distinct abnormality that requires biopsy for diagnosis or confirmation of clinical impression, has histologic features of one or more well-differentiated sebaceous glands that exhibit no fewer than 15 lobules per gland. Sebaceous glands with fewer than 15 lobules that form an apparently distinct clinical lesion on the buccal mucosa are considered normal, whereas similar lesions of other intraoral sites are considered ectopic sebaceous glands. Sebaceous adenomas are less differentiated than sebaceous hyperplasia. PMID- 8469547 TI - Dentigerous cysts in animals. AB - This article is a review of the literature on dentigerous cysts in animals. Three different lesions have been referred to in the veterinary literature as dentigerous cysts. The first of these cysts, similar to those that occur in human beings, is extremely rare. The second lesion, an odontogenic cyst located in the anterior mandibles of mature sheep, is quite common in New Zealand and parts of Britain. The third is actually a teratoma that contains teeth and is found in the temporal region of young horses; it is also rare. PMID- 8469548 TI - Indirect cytotoxic evaluation of dental materials. AB - The standard for cellular biocompatibility in vitro testing is American National Standards Institute/American Dental Association Document No. 41a (1982). The standard allows for the contact testing of solid dental materials for cytotoxicity with HeLa or mouse fibroblasts (L929). The purpose of this study was to evaluate a new method of cytotoxicity testing of biomaterials that allows for an economic standardized indirect cytotoxic screening of the originally dispensed material over a period of time at intervals decided by the investigator. The results show a significant difference of cytotoxicity on the basis of the material between the direct contact method and the indirect or diffusion method described. PMID- 8469549 TI - Cytotoxicity of some modified root canal sealers and their leachable components. AB - The toxic effects of modified endodontic sealers, Fillcanal, N-Rickert, FS, and Sealer 26, were assessed. The material toxicity was measured through radiochromium release method that uses direct and indirect contact methods. The sealers were evaluated freshly mixed and after various setting times. L929 mouse and periodontal ligament fibroblast cells were used as target cells. Fillcanal, N Rickert, and FS showed high toxicity. Fillcanal leaches toxic material when fresh and after setting time. Sealer 26 was the least toxic. PMID- 8469550 TI - Evaluation of the sealing ability of amalgam, Cavit, and glass ionomer cement in the repair of furcation perforations. AB - Perforations created in the pulpal floors of 30 extracted molars were repaired with amalgam, Cavit, and light cured glass ionomer cement. After the pulp chambers and access openings were filled with composite resin, the teeth were then immersed in 2% Erythrocin B solution for 1 week. After longitudinal sectioning of the teeth, dye penetration was measured. The results indicated significant differences between the three materials. Light cured glass ionomer exhibited the least dye penetration followed by Cavit and amalgam. PMID- 8469551 TI - Extraction site healing in rats. A radiologic densitometric study. AB - The present study uses a simple, objective method to radiographically evaluate the changes that occur during socket healing in rats. Mandibular left first molars were extracted in 35 Wistar rats, which were then sacrificed at 0, 7, 14, 21, 28, 45, and 60 days after surgery. Mandibles were removed, placed on an ANSI size 2 film, and exposed with an aluminum step-wedge, 0.5 to 3.0 mm. Socket density was measured with a digital densitometer and related to the equivalent density of aluminum. Increased density of the image of the apical and crestal areas of the socket was observed on day 7. Maximum density was reached by day 28 in the apical area; in the crestal area, density increased at a slower rate. The density changes found in the present study agree with the known histologic reports of socket healing in rats. Densitometric evaluation of extraction socket healing, using a step-wedge with 0.5 mm increments, is a useful and reliable tool to objectively assess bone formation and mineralization. PMID- 8469552 TI - Locating the periapical region in dental radiographs using digital image analysis. AB - An algorithm was designed to automatically obtain information on the orientation of roots in dental radiographs aimed at localizing the periapical region. A curve was approximated mathematically by a cubic polynomial to intersect the boundary of the root at its apex. The performance was judged by comparing the location of this intersection with the actual location of the apex as determined by five expert observers. In an experiment with 262 roots of the eight tooth groups, the distance between these two points was less than 1 mm in 67.9% of all cases and less than 2 mm in 88.2%. The performance of the procedure appeared to depend on the tooth group (p < 0.01). The location of the intersection was reproducible within 1 mm in 86.4% of all cases. The reproducibility was, however, not equal for all tooth groups (p < 0.01). The experts were more consistent in localizing the apex than the system was (p < 0.01), although this difference was not confirmed for four of the tooth groups (p > 0.57), and was marginal for two others (0.01 < p < 0.02). It is concluded that the algorithm is promising in its capacity to track a majority of roots down to their apex. It could therefore add important knowledge to imaging procedures aimed at the digital analysis of the periapical region. PMID- 8469553 TI - Validation of a specific selection criterion for dental periapical radiography. AB - It has been recommended that the prescription of dental radiographic examinations be based on a series of selection criteria. This study evaluated the usefulness of the presence of a large or deep restoration as an indicator for the need for a radiographic examination. Patients in need of routine examinations were questioned regarding pain in restored teeth. The radiographs of 2269 restored teeth in 209 patients were evaluated for depth of restoration and presence or absence of periapical pathosis. Another 1306 nonrestored teeth in 100 patients were evaluated similarly. There was an association between pain and periapical pathosis and between depth of restoration and periapical pathosis (p < 0.001 in each case). Radiographic yield for positive apical findings was low in restored teeth, especially when the restoration was shallow. The radiographic yield may be increased if other factors such as pain or integrity of the restoration are used to help make the decision regarding the need for radiographs. PMID- 8469554 TI - Utilization of radiographs for a state dental board examination. AB - A survey of 97 dentists who had recently taken a state dental board examination was completed to document the use of radiographs for the screening and treatment of their patients. The response rate was 53%. Candidates spent on average 14.25 hours screening a mean of 18 patients to identify the dental pathoses necessary to take the examination. Candidates took a mean of 28.9 (+/- 25.8) radiographs for screening purposes and during the examination with a range of 3 radiographs to a maximum of 141 radiographs. Time in practice and specialty status did not affect the total number of radiographic exposures made. The majority of radiographs taken (53%) were unlikely to be used in the direct care of the patient's dental needs. The results of this survey indicated that efforts to minimize administrative radiographs should be increased. PMID- 8469555 TI - Postextraction osteomyelitis in a bone marrow transplant recipient. AB - This report describes a case of mandibular osteomyelitis after a dental extraction in a patient who subsequently underwent bone marrow transplantation (BMT) for lymphoblastic lymphoma. Surgical guidelines consistent with National Cancer Institute recommendations were followed for the extraction, which was performed before initiation of the myelosuppressive conditioning regimen. However, moderate tenderness developed at the extraction site beginning 10 days after marrow infusion. On day 26 the patient became febrile and blood culture positive for Staphylococcus epidermidis. Radiographs exposed on day 28 demonstrated changes consistent with low-grade osteomyelitis, including diffuse loss of lamina dura and an irregular osseous rarefaction extending 1 cm posterior to the extraction site. Although the indwelling Hickman catheter was the presumed source for bacteremia, clinical and radiographic data led to consideration of mandibular osteomyelitis as an alternative cause. Characteristics of this infection in BMT recipients are reviewed. Recommendations for dental extractions and prophylactic antibiotic regimens for catheterized BMT recipients are also discussed. Although mandibular osteomyelitic lesions are not common in profoundly immunosuppressed BMT recipients, prompt recognition and treatment are essential when the disease occurs. PMID- 8469556 TI - Triamcinolone acetonide versus chlorhexidine for treatment of recurrent stomatitis. AB - This study compared the efficacy of pain control of two medications, used to treat recurrent aphthous stomatitis, placed under a physical barrier of cyanoacrylate. Thirty patients with recurrent aphthous stomatitis were selected from the records of the Diagnostic Referral Clinic at Indiana University School of Dentistry and randomly divided into three groups; one group was a control. Experimental groups received a topical application of either triamcinolone acetonide (0.025%) or chlorhexidine digluconate (0.12%). Medications were covered by isobutyl cyanoacrylate (Iso-Dent). Controls received the Iso-Dent only. Patients kept a diary to record their pain level on a 10 cm visual analog scale until the lesion healed. Ulcer episodes were treated for 12 weeks. Because some patients had multiple episodes, a total of 35 ulcer episodes were available for analysis. The mean number of ulcer days for each group was not significantly different. ANOVA with repeated measures for 10 days on each patient was first performed. A highly significant difference in pain intensity and perception was found at different days (p < 0.0001). No significant difference was found between the triamcinolone acetonide and chlorhexidine gluconate (p < 0.49). PMID- 8469557 TI - Hypodontia and nail dysplasia syndrome. Report of a case. AB - The ectodermal dysplasias are a clinically and genetically heterogeneous group of more than 120 syndromes involving ectodermally derived structures. The syndrome that is autosomal dominantly inherited and characterized by hypodontia, dysplastic nails, and normal hair is known as hypodontia-nail dysplasia syndrome, or tooth-and-nail syndrome. Because of the minimal manifestations, this syndrome may be difficult to diagnose. Patients with hypodontia should be examined for dysplastic nails of the hands and feet and referred to medical and dental genetic specialists for verification of the diagnosis and counseling. We report a case of tooth-and-nail syndrome in a young woman. PMID- 8469558 TI - [Ultrasonic study of the thyroid volume in Budapest children]. AB - The aim of this study was to present the normal thyroid volumes of Budapest school-children (from central- and confine-districts). Real-time ultrasound instrument was used in study of 1328 children. Authors applied the method of Brunn et al. to calculate the size of every single thyroid lobes. Percentile curves of thyroid volumes were prepared on the basis of the results in both sexes and age between 6 and 14 years. Authors refer to the correlation between size of thyroid and (changing) body measurements according to the age and sexes. The frequency of symptomless abnormalities is mentioned in this population supporting the usefulness of thyroid sonography as a screening method. PMID- 8469559 TI - [Diagnosis and treatment of fetal and neonatal tachycardia]. AB - Severe intrauterine cardiac failure due to supraventricular tachycardia in a 29 week fetus was diagnosed using 2 dimensional and Doppler echocardiography. The prenatal tachycardia was successfully treated, the postnatal finding suggested Wolff-Parkinson-White syndrome. The fetal echocardiography by providing information on cardiac structure and haemodynamics may provide diagnostic and therapeutic useful informations. For the optimal pre- and perinatal management of this life-threatening condition absolutely essential a brief collaboration between the pediatric cardiologist and obstetricians. PMID- 8469560 TI - [Curative activity of the physician and alternative methods]. PMID- 8469561 TI - [Centenary of the death of Markusovszky]. PMID- 8469562 TI - [The role of vitamin A analogues and derivatives in the regulation of cell function]. AB - The vitamin A and the retinoids, the vitamin A derivatives play an important role in the embryogenesis, in the modulation of the growth, in the differentiation of normal, premalignant and malignant epithelial and mesenchymal cells and in the maintenance of immune response. The effects of vitamin A are executed by two different mechanisms. While the carotenoids of provitamin A activity and the vitamin A--the retinol--itself are mainly antioxidant molecules and so some of their effects are partly similar to the effects of tocopherol, the retinoids, the derivatives of vitamin A, exert their diverse effects by regulating the expression of specific genes by the aid of specific nuclear receptors belonging to the family of steroid, thyroid hormone, and vitamin D3 receptors. The retinoids play a role in the modulation of the effect of these hormones as well. PMID- 8469563 TI - [Importance of carotid artery studies prior to coronary surgery]. AB - The incidence of cerebral complications following extracorporal cardiac operations is reported to be approximately 2%. One of the possible reasons behind these complications is the presence of significant carotid stenosis as coexistent disease to the cardiac illness requiring surgery. Because of the common etiology carotid stenosis coexists mainly with a coronary artery disease. The authors make known their own screening methods based on the correct exploration of medical history and on the proper physical examinations. Coexistent significant carotid stenosis was revealed in 3.6% of 1056 patients who underwent coronary surgery within the period of 41 months. In all of these cases prophylactic carotid endarterectomy was performed. In twenty cases within this group the carotid reconstructions were performed simultaneously with myocardium revascularization. Staged endprocedures were performed in the other 18 cases. There was no surgical mortality and only one patient suffered major stroke. The authors emphasize the importance of carotid screening among patients awaiting coronary surgery especially in patients who previously sustained cerebral ischemic attacks, the presence of carotid bruits or any other known localization of obliterate arterial disease and finally in all patients over 60 years of age. PMID- 8469564 TI - [Autonomic neuropathy in chronic liver diseases]. AB - Autonomic neuropathy has been evaluated by various cardiovascular bedside tests in 172 patients with chronic alcoholism (36 alcoholics without liver disease, 50 patients with fatty liver and 86 with cirrhosis), in 21 patients with HBsAg positive chronic liver disease, in 14 patients with primary biliary cirrhosis, in 14 patients with cirrhosis of other origin and in 86 healthy controls. Parasympathetic integrity was evaluated by beat-to-beat variation during deep breathing, Valsalva manoeuvre and standing up, sympathetic function by blood pressure response to standing and to sustained handgrip test. Autonomic reflex damage was found in all groups examined. Patients with alcoholic cirrhosis exhibited the most severe alterations. Our results suggest, that chronic hepatopathy itself presents a pathogenetic factor of autonomic neuropathy. Autonomic failure has to be considered as a possible cause of symptoms in liver diseases with all its prognostic consequences. PMID- 8469565 TI - [Dysfunction of penile erection]. AB - Nearly 250 men with erectile dysfunction examined during the past 3 years period. Beside the examination technique development the author emphasizes on the importance of the medical history and the psychological exploration. The examinations are indicated after the analysis of the history and after the positive result of the noninvasive examination the invasive one is only indicated. Intracavernous injection of the vasoactive drugs remains important part of the diagnosis, but the combination with the Doppler examination gives more information about the origin of the dysfunction. PMID- 8469567 TI - [Pathography on Csontvary medals]. PMID- 8469566 TI - [Etretinate therapy of papillomatosis cutis carcinoides]. AB - The authors review the case-history of a 67-year old female patient suffering from papillomatosis cutis carcinoids. They present other pathographies found in the pseudocancerosis group, and their transformation into praecancerosis. They give an account of the successful treatment of cases classified under the pseudocancerosis group with etretinate. They further call attention to the wide spread applicability of retinoids. PMID- 8469568 TI - [A journal by medical students from the beginning of the century]. PMID- 8469569 TI - ONS members observe health care in former Soviet Union. PMID- 8469570 TI - So who needs a bronchoscope, anyway? PMID- 8469571 TI - Developmental control of collagen gene expression in the rat lung: confirmation of early observations of lung growth. AB - The short gestation period of the rat allows one to see rapid morphologic and biochemical changes in the lung. It has been shown that the rat lung undergoes a period of distension over the first several days of life followed by a rapid alveolar growth. Total lung collagen also increases during this time period. We have examined the changes in types I and III procollagen transcripts during the perinatal period and have compared them to the above observations. Total RNA was extracted from the lungs of offspring of time-pregnant Sprague-Dawley rats after large airways were removed. Northern hybridization was performed to determine the quality of steady-state RNA and rule out cross-hybridization while densitometric tracings of slot-blot hybridizations allowed comparative estimates of the target sequence of RNA. Immediately following birth, the steady-state mRNA procollagen levels increased and a shift to a predominant type I production occurred. These changes preceded the rapid increase of collagen content and alveolarization known to occur at three days of age. These data provide further evidence that collagen production is controlled at the level of transcription and in temporal and tissue specific manners. PMID- 8469572 TI - Poor agreement between reported and recorded nocturnal cough in asthma. AB - Reported presence or absence of night cough was compared with tape recorded cough in 15 children with perennial asthma (median age, 9 years; range, 7-14) who reported troublesome nocturnal symptoms. Measurements were made and diaries kept for 7 consecutive nights. Cough was reported on 66 of 105 (66%) and recorded on 93 (90%) available nights with poor overall agreement (Cohen's coefficient of assessment, kappa +0.30, range -0.17 to +1). The poor agreement between subjective and objective assessment of an important symptom of nocturnal asthma raises questions on the validity of symptom reporting and may in part explain the not infrequent disagreement between medical and patient assessment of disease severity. PMID- 8469573 TI - Postnatal expression of myosin isoforms in the genioglossus and diaphragm muscles. AB - We studied the expression of myosin heavy chain (MHC) and native myosin isoforms in the genioglossus (GG) and costal diaphragm (DIA) muscles of the rat during postnatal development using both denaturing and nondenaturing gel electrophoresis. Primary myotubes in both fast and slow muscles homogeneously express slow as well as embryonic myosin. Since the adult GG is comprised primarily of fast MHC isoforms, whereas the adult DIA is characterized by a mixture of MHC slow and fast isoforms, we hypothesized that the GG and DIA would be subject to different temporal patterns of MHC isoform expression during postnatal development. Native myosin and MHC gels demonstrated a persistence of neonatal MHC (MHC neo) on day 25 in the GG, whereas this isoform was not detected beyond day 21 in the DIA. The MHC phenotype in GG of the adult demonstrated a predominance of MHC 2X (35% +/- 8) and MHC 2B (45% +/- 10) with a smaller proportion of MHC 2A (19% +/- 5). In contrast, the MHC phenotype in adult DIA was characterized by approximately equal proportions of MHC slow (25% +/- 3), MHC 2A (34% +/- 10), and MHC 2X (31% +/- 12) with a small percentage of MHC 2B (9% +/- 7). These data suggest that postnatal regulation of MHC expression in the GG and DIA is muscle specific. PMID- 8469574 TI - Assessment of forced expiratory volume-time parameters in detecting histamine induced bronchoconstriction in wheezy infants. AB - A new technique recently introduced allows the measurement of infant lung function from lung volumes raised by a pump prior to generation of forced expiratory flow-volume (FEFV) curves. Forced expiratory volume-time (FEV1) parameters rather than traditional flow parameters are used. The aim of this study was to assess the usefulness of FEV1 parameters in detecting airway responsiveness to histamine in recurrently wheezy infants. Ten infants (age 7-18 months) sedated with 80 mg/kg chloral hydrate underwent a histamine inhalation challenge. Throughout the challenge FEFV curves were generated from end-tidal inspiration. Raised FEFV curves, from a lung volume preset by 15 cmH2O inflation pressure, were gathered at baseline and after the final concentration of histamine. The mean fall from baseline was 47% in maximal flow at functional residual capacity (VmaxFRC) (P < 0.0005), 15.5% in FEV0.5 (P < 0.0001), 13.5% in FEV0.75 (P < 0.005), and 11.0% in FEV1.0 (P = 0.057), after the final concentration of histamine delivered. Tidal volume and inspiratory volume reached above FRC between pre- and posthistamine did not change. Mean oxygen saturation fell significantly from 97 to 93%. We conclude that FEV1 parameters adequately detect reduced lung function during histamine-induced bronchoconstriction and appear suitable for histamine challenge testing in infants. PMID- 8469575 TI - Compliance of the respiratory system in newborn infants pre- and postsurfactant replacement therapy. AB - Surfactant administration causes a rapid and dramatic improvement in gas exchange, but paradoxically, studies have failed to show an improvement in the mechanical properties of the lung. We have measured dynamic and static (passive flow-volume technique) compliance before and after a single dose of bovine lipid extract surfactant in 22 premature infants with RDS. This had no effect on the measured dynamic compliance. In contrast, surfactant significantly increased static compliance from 0.41 +/- 0.02 to 0.55 +/- 0.04 mL/cm H2O/kg. This improvement was the result of a substantial recruitment of lung volume after surfactant administration. This led us to reduce ventilator pressures, which produced an increase in both dynamic and static compliance, but did not recruit additional volume. We conclude that surfactant causes a substantial increase in static compliance due to volume recruitment, which is consistent with reports of increase in the measured FRC. However, despite this improvement, the compliance is still below our normal range. PMID- 8469576 TI - Radiographic evidence of bronchopulmonary dysplasia in high-risk congenital diaphragmatic hernia survivors. AB - Congenital diaphragmatic hernia is a congenital malformation associated with pulmonary hypoplasia. It often leads to respiratory failure, requiring artificial ventilation with high inflation pressures and high percentages of oxygen. We evaluated radiographic evidence of bronchopulmonary dysplasia (BPD) in survivors, who presented with respiratory distress within 6 hours after birth, by a radiographic scoring system measuring the severity of BPD by the Toce score and the degree of pulmonary hypoplasia by the Touloukian score. Fifteen of 45 survivors (33 percent) had clinical and radiological lung disease resembling BPD. As a group they had significantly higher Touloukian and Toce scores than survivors without BPD. Morbidity expressed as the duration of artificial ventilation, supplemental oxygen, and hospital stay was much higher in the BPD group. The hypoplastic lung in infants with congenital diaphragmatic hernia appears to be as susceptible to barotrauma and pulmonary oxygen toxicity as the lungs of prematurely born infants. To what extent BPD occurring in congenital diaphragmatic hernia survivors might influence the future development of lung function is not yet known. PMID- 8469577 TI - Fluid dynamics during initial aeration of mature fetal lung and effect of temperature. AB - Air volume-pressure (VP) curves were recorded simultaneously on pairs of mature rabbit fetuses from the same litter with one member of the pair at 37 degrees C and the other at 22 degrees C. Intrasaccular bubbles, formed primarily during inflation, were assessed for stability and surface tension (gamma). Average air flow rates (dV/dt) were calculated from the VP data. In separate experiments, liquid VP curves were recorded at 37 degrees and 22 degrees C: maximal liquid V was matched to maximal air V at 37 degrees and 22 degrees C, respectively. Fetal pulmonary liquid (FPL) viscosity (eta) and density (rho) were determined by standard methods. Both the effect of temperature on lung mechanics as reported previously, and the reliability of the rabbit model were confirmed in the paired fetuses. Analysis of fluid dynamics revealed that of the six parameters relevant to initial inflation-deflation of FPL-filled lungs, liquid rho, distensibility (recoil), and gamma were not altered significantly by temperature increase from 22 degrees to 37 degrees C. Enhanced lung mechanics at 37 degrees C (including enhanced inflation at lower P, higher maximal V, increased production of intrasaccular bubbles, and higher V at end-deflation) was primarily due to lowering of FPL eta at the higher temperature which appears to have an effect by augmenting bulk liquid flow and liquid drainage. Lower eta increases bulk flow through airways directly. Consequent recruitment and distention of these conducting units effectively increases radius (r) and further enhances flow. (The ultimate "brake" to airways flow at both temperatures is counter P from gamma at air/liquid menisci.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469578 TI - Comparison of the squeeze technique and transcutaneous oxygen tension for measuring the response to bronchial challenge in normal and wheezy infants. AB - The aim of this study was to compare the fall in transcutaneous oxygen tension (PtcO2) as an outcome measure during bronchial provocation with histamine, with changes in airway function measured by the squeeze technique in healthy infants and those with wheezing disorders. PtcO2 was measured during histamine challenge in 20 infants, aged 6-16 months, of whom 14 had recurrent cough or wheeze (lower respiratory illness, LRI), and 6 were healthy. All were symptom free at the time of testing. The minimum value of PtcO2 after each nebulization was compared with the minimum baseline value. The response to increasing concentrations of histamine was also assessed by measuring maximal flow at functional residual capacity (VmaxFRC) by the squeeze technique. The inhaled concentration of histamine causing a 30% fall in VmaxFRC was calculated to give the provoking concentration (PC30). Baseline VmaxFRC was lower in symptomatic infants (117 mL/s) than the normal infants (322 mL/s; P < 0.005), but the PC30 was not significantly different (7.7 and 5.7 g/L, respectively). There was no difference in baseline PtcO2 between the two groups. The infants with LRI had significant reductions in PtcO2 at both the final and preceding concentrations of histamine, whereas the normal infants had a significant and smaller reduction in PtcO2 only at the provoking concentration. Reduction in PtcO2 during bronchial challenge was a less sensitive index of bronchial response in healthy infants than in infants with a history of recurrent LRI. PMID- 8469579 TI - Nonbronchoscopic bronchoalveolar lavage in mechanically ventilated infants: technique, efficacy, and applications. AB - Bronchoalveolar lavage with the fiberoptic bronchoscope is commonly used for the diagnosis of pulmonary infections in mechanically ventilated adults and children. However, its use for intubated infants is precluded because the small artificial airway does not permit the passage of the bronchoscope. We have developed a technique for nonbronchoscopic bronchoalveolar lavage, performed via a sterile, disposable feeding tube. We have used this technique in 15 infants with diffuse interstitial disease and/or atelectasis, while they were intubated and mechanically ventilated. The volume of the lavage effluent averaged 70.3% of the volume instilled. Specific diagnosis on the basis of the cytologic evaluation and/or culture of the lavage fluid was possible in 9 (60%) patients. Two patients with atelectasis showed radiographic evidence of improvement following the procedure. There were no complications. We conclude that nonbronchoscopic bronchoalveolar lavage is well tolerated, and clinically useful in small, mechanically ventilated infants with respiratory failure due to diffuse pulmonary disease. This technique provides a lower risk alternative to more invasive, and costly procedures. PMID- 8469580 TI - Subclinical infantile Chlamydia trachomatis pulmonary infection. PMID- 8469581 TI - Report of a weekly New England pediatric pulmonary conference case report: lung cavity in a child. PMID- 8469582 TI - CT of blunt chest trauma in children. AB - While trauma is still the leading cause of death in the pediatric age range, it is surprising how little the CT appearances of pediatric chest injury have been investigated in the literature. We have reviewed the CT findings of blunt chest trauma in 44 children for whom chest CT examinations were requested to investigate the extent of intrathoracic injury. We noted a propensity for pulmonary contusions to be located posteriorly or posteromedially, and for them to be anatomically nonsegmental and crescentic in shape. This is possibly attributable to the relatively compliant anterior chest wall in children. The CT appearances of other major thoracic injuries are described, including pulmonary lacerations, pneumothoraces, malpositioned chest tubes, mediastinal hematomas, aortic injury, tracheobronchial injury, hemopericardium, and spinal injuries with paraspinal fluid collections. Children demonstrating findings incidental to the actual injury yet important to the subsequent therapy are also presented. We conclude that, in the event of clinically significant blunt chest trauma, the single supine chest examination in the trauma room is insufficient to adequately identify the extent of intrathoracic injury. With the exception of concern for aortic injury for which aortography is indicated, a dynamically enhanced CT scan of the thorax should be performed as clinically significant findings may result in altered therapy. PMID- 8469583 TI - Progressive noninfectious anterior vertebral fusion: MRI findings and association with a lipoma of the filum terminale in a 5-year-old girl. AB - Progressive noninfectious anterior vertebral fusion (PNAF) is a rare but well defined entity of unknown cause. We report the MRI findings in a 5-year-old in whom PNAF was associated with a lipoma of the filum terminale. PMID- 8469584 TI - Findings on magnetic resonance imaging of the spine and femur in a case of McCune Albright syndrome. AB - Polyostotic fibrous dysplasia, a major osseous change in McCune-Albright syndrome, is seen in the cranium, facial bones, bones of the extremities, and ribs, but rarely in the spine. Spinal X-rays revealed no abnormalities in an 8 year-old girl with this syndrome, but 99mTc-methylene diphosphonate bone scintigraphy disclosed high-density areas in the thoracic and lumbar vertebrae. Multiple well-circumscribed areas of low signal intensity were seen on T1 weighted magnetic resonance imaging (MRI) of the spine. Although MRI spine scans in this disease have never been reported, our findings in this case proved interesting for evaluating osseous lesions. MRI made it possible to differentiate between fibrous lesions (low signal intensity on T1- and T2-weighted MRI) and cartilaginous lesions (low signal intensity on T1-weighted MRI and high signal intensity on T2-weighted MRI). PMID- 8469585 TI - Development of late congenital hip dysplasia: significance of ultrasound screening. AB - Ultrasound for detecting congenital hip dysplasia was performed in 5970 infants, 2121 of whom were reinvestigated. Of those reinvestigated 726 belonged to the screened group not at risk examined as newborns, 70 were infants at risk first investigated as newborns and 363 were infants at risk first examined after the newborn period; the remainder were infants not at risk first investigated after the newborn period. Pathological findings were obtained in 7.7% of the entire group, in 3.9% of children at no risk, and in 5% of patients at risk. Deterioration of Graf's classification of types was seen in 3.2%. 13 children, 3 of the screened group and 10 of the nonscreened group developed hip dysplasia. None of them would have been missed since they were borderline type IIA on at least one side, which warranted mandatory follow-up. PMID- 8469586 TI - Retrograde percutaneous gastrostomy: a prospective study in 57 children. AB - We prospectively studied Retrograde Percutaneous Gastrostomy (RPG) in 57 children (age 3 weeks-17 years, 1.7-48 kg) as the feasibility and complications of this technique have not been reported in a large series of children. We used IV sedation (42), oral sedation (4 neonates), general anaesthesia or local anaesthesia only. The retrograde approach for gastrostomy or gastrojejunostomy catheter placement is described. Catheter placement was unsuccessful in only one child, due to the presence of marked hepatosplenomegaly. Catheters were successfully placed in all the other 56 children. In one of these, catheter misplacement occurred due to retraction of the stomach from the anterior abdominal wall during its insertion. This was recognized during the procedure. The catheter was removed and reinserted on the same occasion. One catheter was accidentally pulled out after six days and was subsequently replaced. Two children had mild, local abdominal tenderness and fever for up to 48 hours but post procedure septicemia or significant infection were not encountered. All children benefitted from gastrostomy feeding and gained weight. PMID- 8469587 TI - Correlation of gastric emptying at one and two hours following formula feeding. AB - The acquisition of gastric emptying (GE) data by scintigraphy has become an important component of the evaluation of the pediatric patient for gastroesophageal reflux (GER). Delay of GE can contribute to ongoing gastric distension and hence increase propensity to reflux. Generally, only 1 h GE is determined during scintigraphy. Infants with GER have variable patterns of symptoms: some have spitting, vomiting, choking, and/or apparent life-threatening events in the immediate post-prandial period only, whereas in others symptoms persist until the time of next feeding. It is not clear whether differential rates of GE contribute towards such disparity of symptoms. We performed this prospective study to determine the correlation between GE at 1 h or 2 h, respectively, and for 2 h following a feeding in 27 infants under one year of age, who were referred for evaluation of GER. Continuous scintigraphy was performed for 2 h following a formula feeding. Gastric emptying at 1 h was calculated as percent of original dose emptied by 60 min; GE at 2 h was calculated as percent of isotope remaining in the stomach at 60 min which was emptied by 120 min. The median GE between 0 to 60 min was 36% (95% CI 26.0-42.0) and median GE of the residual formula between 60 to 120 min was 45% (95% CI 34.3 51.3). The correlation coefficient of GE, at 1 h with total GE over 2 h was 0.75 and of GE during the 2nd h with total GE over 2 h was 0.76. We conclude that routine determination of GE for 2 h continuously does not appear to offer clinically significant additional information. PMID- 8469588 TI - Calcification of scleral-wrapped orbital implant in patients with retinoblastoma. AB - Calcification detected by CT is a valuable technique to confirm a clinical impression of retinoblastoma. However, when calcification is detected following enucleation with placement of a scleral-wrapped orbital implant, the presence of calcium may be dystrophic, instead of indicating recurrent tumor growth. Cautious follow-up is warranted, and this report suggests that such calcification, probably associated with the scleral wrapping, can remain stable over many years. PMID- 8469589 TI - Smith-Lemli-Opitz syndrome type II: report of a case with additional radiographic findings. AB - A phenotypically female infant with 46-XY chromosomes was found to have Smith Lemli-Opitz syndrome, type II a rare congenital malformation syndrome with many features of the more common classic Smith-Lemli-Opitz syndrome. The patient's skeletal survey revealed characteristic and previously undescribed skeletal anomalies which are reported. In addition a lipoma of the pituitary gland was found on magnetic resonance imaging. This lesion is particularly interesting given the hypothesized steroid abnormality in Smith-Lemli-Opitz, type II syndrome, the sexual ambiguity of males with this syndrome and the similarity of this syndrome to the Pallister-Hall syndrome which characteristically has a hamartoblastoma of the hypothalamus. PMID- 8469590 TI - Unusual manifestations of Langerhans cell histiocytosis of the head and neck. Case report with pseudoaneurysm of external carotid artery, tracheal, mandibular, and sphenoid involvement. AB - Langerhans cell histiocytosis of the head and neck is an uncommon histiocytic proliferative disorder that often clinically resembles an inflammatory process. A pseudoaneurysm of the external carotid artery was found by contrast-enhanced CT and confirmed by Doppler ultrasonography and angiography in a 9 year old girl with a lytic lesion of the mandible, a prior severe tracheal inflammatory process, and sclerotic lesions of the sphenoid wings. Biopsies of the mandibular lesion, pseudoaneurysm, and trachea demonstrated Langerhans cell histiocytosis. In cases of LCH with head and neck involvement, contrast-enhanced CT allows adequately detailed initial evaluation of the protean manifestations of this disorder. PMID- 8469591 TI - Horseshoe lung--a case report with unusual bronchial and pleural anomalies and a proposed new classification. AB - One case of horseshoe lung with associated scimitar syndrome is presented. Unusual bronchial and pleural anomalies as delineated by CT and plain chest radiographic imaging are described. The presence of bilateral fissures led to a newly proposed classification of horseshoe lung based on pleural anatomy. PMID- 8469592 TI - Congenital double pylorus with accessory pyloric channel communicating with an intraluminal duplication cyst of the duodenum. AB - Congenital double pylorus is a rare anomaly in which two pyloric openings connect the antrum of the stomach to the duodenal bulb. We report an unusual case of congenital double pylorus in which one of the channels led to an intraluminal cystic duplication of the duodenal bulb. An embryologic relation between congenital double pylorus and antroduodenal duplications is suggested. PMID- 8469593 TI - Ilio-psoas abscess in neonates. AB - We report two cases of primary ilio-psoas abscess in neonates diagnosed by CT and sonography. Ilio-psoas abscess is extremely uncommon in this age group. PMID- 8469594 TI - White matter change on CT associated with superior vena cava syndrome: a case report. AB - An 11-year-old Japanese girl with nephrotic syndrome developed superior vena cava syndrome associated with hypercoagulability and an indwelling catheter. Cranial CT revealed diffuse low-density lesions in paraventricular white matter. Thrombectomy brought prompt relief of symptoms and correction of CT abnormalities. PMID- 8469595 TI - Endodermal sinus (yolk sac) tumor of vagina and cervix in an infant. AB - A case of vaginal and cervical endodermal sinus (yolk sac) tumor in a 6-month-old female infant is reported. The patient presented with an intermittent bloody discharge on her diapers. Pelvic CT showed an irregular soft tissue density mass with heterogeneous enhancement within the vagina and extending to the cervix. The histopathologic features were identical to those of endodermal sinus tumors. PMID- 8469596 TI - Endodermal sinus tumour associated with benign teratoma of the common bile duct. AB - We report a 5-year-old boy with endodermal sinus tumour associated with benign cystic teratoma of the common bile duct (CBD). To our knowledge, there has been one case of teratoma of the CBD in the English literature with no morphological or radiological description. Our case presented a lobulated polypoid mass obstructing the distal CBD on sonography and computed tomography, which resembled the botryoid masses of rhabdomyosarcoma. PMID- 8469597 TI - Radiological evaluation of pulmonary vein obstruction including two examinations by magnetic resonance imaging. AB - Congenital obstruction of the pulmonary vein without anomalous drainage can cause long-standing pulmonary congestion and pulmonary arterial hypertension, and it may include stenosis of individual pulmonary veins and pulmonary vein atresia. We reviewed seven cases of pulmonary vein obstruction, five of which were accompanied by other cardiac anomalies. Right pulmonary veins were involved in all seven cases; one case was bilateral. Pulmonary veins were occluded totally in five and partially in three lungs. Diagnostic pulmonary catheterization and angiography were performed. Chest radiographs of total occlusion cases showed decreased lung volume, features of pulmonary edema, interstitial lesions, and pleural changes, which were quite specific, whereas pulmonary venous dilatation was the dominant finding in partial obstruction cases. Pulmonary perfusion scan (n = 3) showed total perfusion defects in the cases with total occlusion of pulmonary veins. Magnetic resonance (MR) imaging (n = 2) demonstrated totally occluded pulmonary veins at the venoatrial junction in two lungs and membranous focal obstruction in one lung. Two children underwent pneumonectomy and had the diagnosis histologically confirmed. Although catheterization and angiography are essential for the diagnosis of pulmonary vein obstruction, MR imaging is a useful adjunct. PMID- 8469598 TI - CT, MRI, and color Doppler ultrasound correlation of pancreatoblastoma: a case report. AB - Pancreatic neoplasms in childhood are rare but should be considered in the differential diagnosis of masses in the region of the lesser sac. A case of pancreatoblastoma in a 3 1/2-year-old boy is presented. The patient was studied with US, CT, and MR imaging. PMID- 8469599 TI - Prenatal diagnosis of colon atresia. AB - We report a case of colon atresia diagnosed pre-natally at 32 weeks' gestation. The fetal transverse colon was dilated. Complete atresia of the middle transverse colon was confirmed after birth. Small bowel dilatation (and clinical obstruction) did not develop until after 24 h of age. PMID- 8469600 TI - Darrow-Gamble disease: ultrasonographic and radiographic findings. AB - A case of Darrow-Gamble disease is presented with review of the radiographic and ultrasonographic appearance of this rare cause of profound chronic diarrhea beginning at birth. The disease is caused by a defect of active intestinal chloride transport which results in a large loss of the electrolytes and water. To prevent growth retardation and renal involvement an adequate replacement therapy is necessary. This uncommon anomaly was detected by ultrasound 3 weeks before delivery. Both sonography and radiography were useful diagnostic tools in the postnatal period. The clinical features of the lesion are also discussed. PMID- 8469601 TI - Prenatal diagnosis of diastematomyelia. AB - Fetal diastematomyelia, a malformation due to a longitudinal split of the cord, was diagnosed during the third trimester. Diagnosis was based on the visualization of a sagittal bony spur in the thoracolumbar spinal canal, associated with enlargement of the canal, hemivertebrae and spina bifida without a meningocele. PMID- 8469602 TI - Prenatal diagnosis of unilateral hydrocephalus. AB - We report a case of unilateral hydrocephalus diagnosed at 20 weeks' gestation, at which time marked facial and cranial asymmetry was present already. Brain mantle reconstitution was incomplete following ventriculo-peritoneal shunting, and the child has significant neurodevelopmental disability. PMID- 8469603 TI - Epiglottic enlargement secondary to laryngeal sarcoidosis. AB - A case of laryngeal sarcoidosis manifesting as epiglottic enlargement in a 15 year-old boy is presented. Sarcoidosis of the larynx is unusual in children but should be included in the differential diagnosis of epiglottic enlargement. PMID- 8469604 TI - Ultrasonography of acute epitrochlear lymphadenitis. AB - While the clinical symptomatology and radiographic findings of acute suppurative infection of the epitrochlear lymph nodes of the arm have been previously described, ultrasonographic findings have not been reported. This case report demonstrates that sonographic identification of enlarged epitrochlear lymph nodes immediately confirms the diagnosis. We summarize the clinical, radiological, and sonographic findings of acute suppurative infection of the epitrochlear lymph nodes. PMID- 8469605 TI - Osteosarcoma with calcified regional lymph nodes. AB - A case of osteosarcoma of osteoblastic type with inguinal calcified lymphadenopathy is described. The primary lesion of the distal left femur was treated with limb-sparing surgery. Chemotherapy was given before and after the surgical procedure. Metachronous calcified lymph node metastases were seen on plain radiography, computed tomography and bone radionuclide scan. The patient is alive and free of disease more than 40 months after lymphadenectomy and radiotherapy of regional node metastases. PMID- 8469606 TI - Burkitt's lymphoma with mandible, intra-abdominal and renal involvement--initial presentation of HIV infection in a 4-year-old child. AB - Burkitt's lymphoma of the jaw was first described as a jaw tumor occurring endemically in African children. We report a case of Burkitt's lymphoma in a child presenting with a painful jaw mass which proved to be Burkitt's lymphoma; renal involvement was also noted. The child was found to be HIV positive. Burkitt's may be the initial manifestation of HIV infection in the pediatric population. PMID- 8469607 TI - Current radiological management of intussusception. PMID- 8469608 TI - Thapsigargin discharges intracellular calcium stores and induces transmembrane currents in human endothelial cells. AB - We have measured the effects of thapsigargin, a specific inhibitor of endoplasmic Ca(2+)-adenosine 5'-triphosphatase (Ca(2+)-ATPase), on membrane currents and on the intracellular Ca2+ concentration ([Ca2+]i) in single endothelial cells from the human umbilical cord vein. Currents were recorded by means of the patch-clamp technique in the whole-cell mode and [Ca2+]i was measured using Fura II. Application of thapsigargin at concentrations between 0.2 and 2 mumol/l induced a slow increase in [Ca2+]i to a peak value of 400 +/- 110 nmol/l above a resting level of 120 +/- 35 nmol/l, and then slowly declined to a new steady-state level of 315 +/- 90 nmol/l (n = 33). The thapsigargin-induced increase in [Ca2+]i depended on the extracellular Ca2+ concentration ([Ca2+]o: it declined after removal of extracellular Ca2+, but increased again when [Ca2+]o was augmented, indicating that the response depends on a transmembrane influx of Ca2+ ions. The peak amplitude of the histamine-induced Ca2+ transient was reduced in the presence of thapsigargin. This reduction was more pronounced when histamine was applied at the peak of the increase in [Ca2+]i induced by thapsigargin than during the rising phase of the changes in [Ca2+]i. The decline of the Ca2+ transient induced by histamine after washing out the agonist was also affected by thapsigargin. Before application of thapsigargin, this decline could be described by a single exponential with a time constant tau equal to 24.5 +/- 5 s (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469609 TI - Genetic regulation of enterocyte function: a quantitative in situ hybridisation study of lactase-phlorizin hydrolase and Na(+)-glucose cotransporter mRNAs in rabbit small intestine. AB - The enterocyte undergoes sequential changes in its structure and function as it migrates rapidly from the small intestinal crypts to the villus tip. The mechanisms by which these changes are regulated "in tune" with ontogenic and dietary changes in the luminal environment are currently under investigation. This study has employed oligonucleotide probes to follow the expression of the lactase-phlorizin hydrolase (LPH) and Na(+)-glucose cotransporter (SGLT1) genes in rabbit small intestine using quantitative in situ hybridisation histochemistry. The profiles of LPH mRNA and SGLT1 mRNA accumulation along the crypt-villus axis were found to be very similar. Although mRNA was undetectable in the crypt. LPH and SGLT1 mRNA levels rose rapidly at the crypt-villus junction, reaching a maximum between 210 microns and 330 microns above this point. Further up the villus the level of mRNAs declined. SGLT1 mRNA was present in all small intestinal segments (duodenum, jejunum and ileum), whereas LPH mRNA was absent from the ileum. LPH activity rose and fell in conjunction with mRNA, but SGLT1 activity was greatest at the villus tip where mRNA levels were considerably reduced. These data have been used to discuss the genetic regulation of enterocyte differentiation and function. PMID- 8469610 TI - Activation of the nicotinic acetylcholine receptor mobilizes calcium from caffeine-insensitive stores in C2C12 mouse myotubes. AB - In cultured mouse C2C12 myotubes, digital Ca2+ imaging fluorescence microscopy using the acetoxymethyl ester of Fura-2, Fura-2-AM, showed that, in the absence of extracellular Ca2+, acetylcholine (ACh) and nicotine, but not muscarine, raised the intracellular concentration of Ca2+ ([Ca2+]i) by about tenfold. ACh induced Ca2+ mobilization was prevented by thapsigargin, a drug known to deplete inositol 1,4,5-trisphosphate (InsP3)-sensitive stores, and was concomitant with InsP3 accumulation. Caffeine, which releases Ca2+ from the ryanodine-sensitive stores of the sarcoplasmic reticulum, did not interfere with the ACh-induced [Ca2+]i increase. Ca2+ mobilization was also inhibited when myotubes were depolarized by high K+, or when extracellular Na+ was omitted. Nicotinic ACh receptor (nAChR) stimulation lowered intracellular pH with a time course slower than the [Ca2+]i increase. Possible mechanisms linking the current flowing through the nAChR pore to [Ca2+]i increase are discussed. PMID- 8469611 TI - Sarcoplasmic reticulum calcium mobilization in right ventricular pressure overload hypertrophy in the ferret: relationships to diastolic dysfunction and a negative treppe. AB - In a model of right-ventricular pressure-overload hypertrophy (POH) in the ferret, action potential duration (to 90% repolarization) was found to be significantly longer (228 +/- 11 vs 314 +/- 12 ms) with no change in amplitude (85 +/- 3 vs 85 +/- 2 mV) or resting membrane potential (-79 +/- 1.5 vs -79 +/- 1 mV) for control and POH, respectively. Peak sarcoplasmic reticulum Ca2+ release (expressed as the logarithm of the fractional luminescence, -4.2 +/- 0.1 vs -4.4 +/- 0.3) and resting calcium concentrations (-5.5 +/- 0.1 vs -5.7 +/- 0.1) were not different between the two groups (control vs POH respectively). Muscles from control and POH animals demonstrated a positive force/interval relationship in the presence of physiological extracellular [Ca2+]. However, unlike muscles from control animals, muscles from animals with POH subjected to increasing frequencies of contraction in the presence of increased extracellular [Ca2+] demonstrated further impairment of diastolic relaxation and a negative treppe. Exposure of muscles from POH animals to isoproterenol returned the slowed Ca2+ uptake by the sarcoplasmic reticulum as detected with aequorin to control values, although the relaxation phase of the isometric twitch remained prolonged compared to non-hypertrophied muscles. Exposure to milrinone also abbreviated the time course of the intracellular Ca2+ transient, but did not return it to that seen in normal myocardium. The exposure of non-hypertrophied isolated muscles to caffeine resulted in similar prolongation of the isometric twitch duration to that seen in hypertrophied myocardium. Results of these experiments suggest that impaired muscle relaxation in POH reflects changes at the level of the myofilaments. Thus, although slowed intracellular calcium mobilization contributes to diastolic relaxation abnormalities, it can not be the sole factor responsible for the slowed relaxation as has been suggested. PMID- 8469612 TI - A method for rapid exchange of solutions at membrane patches using a 10 microliters microcapsule. AB - A rapid exchange (less than 2 ms) of the bath solution facing a membrane patch is accomplished by driving the tip of a pipette from the bath through a 100-microns oil layer into a small capsule filled with 10 microliters test solution. The microcapsule method can be applied to both excised patch configurations, inside out and outside-out patches. On and off reactions of Ca(2+)-activated K+ channel activity have been recorded after changing the intracellular Ca2+ concentration using an inside-out patch. A blockade of these K+ channels by external tetraethylammonium ions is demonstrated with an outside-out patch. The blocking kinetics of delayed-rectifier K+ channels by a purified peptide toxin from snake venom, dendrotoxin, could be measured with our microcapsule method. Using tiny volumes of test solutions this method can be helpful in experiments involving scarce or expensive solutions. PMID- 8469613 TI - Trypsin and alpha-chymotrypsin treatment abolishes glibenclamide sensitivity of KATP channels in rat ventricular myocytes. AB - Cytoplasmic trypsin-treatment of voltage-sensitive potassium channels has been shown to cleave domains of the channel responsible for inactivation of the channel. Trypsin has also been reported to remove slow, irreversible inactivation, or run-down in ATP-sensitive potassium (KATP) channels. Cytoplasmic treatment of rat ventricular KATP channels with either crude, or pure trypsin (1 2 mg/ml) failed to prevent a slow run-down of channel activity. However, trypsin (porcine pancreatic type IX, or type II (Sigma Chem. Co.), or alpha-chymotrypsin (Sigma Chem. Co.) rapidly and irreversibly removed, or substantiallly decreased glibenclamide and tolbutamide-sensitivity of the channels without removing sensitivity to ATP. We conclude that glibenclamide must bind to either a separate protein, or to a separate domain on the channel in order to effect channel inhibition, and this domain is functionally disconnected from the channel by trypsin-, or alpha-chymotrypsin treatment. PMID- 8469614 TI - Community health nursing: shelter from the storm. PMID- 8469615 TI - New Jersey State Nurses' Association history: what is past is prologue. The sixth decade ... 1953-1962. PMID- 8469616 TI - Peer assistance. Prevention techniques that can be implemented without formal instruction. PMID- 8469617 TI - Games nurses play. PMID- 8469618 TI - Candidal urinary tract infections: a comprehensive review of their diagnosis and management. AB - Despite its prevalence, the significance of candiduria remains uncertain. The pathogenesis of candidal urinary tract infections has been relatively well characterized and many risk factors have been identified. The disorders lack consistent diagnostic criteria, however, such as the presence of pyuria or a colony count above which is predicative of presence, location, or severity of infection. Treatment is unclear due to lack of data defining the natural progression of the disease. Although often recommended, it may not always be possible to remove risk factors. Amphotericin B, fluconazole, 5-flucytosine, and other antifungal agents are important agents for managing candidal urinary tract infections. PMID- 8469619 TI - Monoclonal antibody therapy for gram-negative sepsis: principles, applications, and controversies. AB - Gram-negative sepsis is a common event in hospitalized patients and is a leading cause of death in the United States. Endotoxin (lipopolysaccharide, LPS), a component of the cell wall of gram-negative microorganisms, is responsible for the cascade of events leading to the sepsis syndrome consisting of fever, tachycardia, tachypnea, and evidence of organ hypoperfusion. The lipid A region of endotoxin produces most of these biologic and toxic effects. Monoclonal IgM antibodies directed against the lipid A portion of endotoxin (anti-LPS MoAb) have been developed for the treatment of gram-negative sepsis. Results of two large scale clinical trials suggest that these antibodies offer clinically and statistically significant reductions in mortality by a factor of about one-third. However, in both trials, this apparent beneficial effect was limited to particular subsets of patients, and no overall benefit was seen. These considerations, in addition to the likely high cost of the agents, pose questions about their ultimate use in the treatment of patients with gram-negative sepsis. Nevertheless, the logic of the approach, the demonstration of efficacy in disease models, and the advances in modern techniques of molecular biology all suggest that these or other closely related products will play a significant role in the treatment of this disorder. PMID- 8469620 TI - Accuracy of 2- and 8-hour urine collections for measuring creatinine clearance in the hospitalized elderly. AB - The accuracy of 2- and 8- hour urine collections for estimating creatinine clearance was compared with that of the standard 24-hour procedure in 45 hospitalized elderly patients (age > or = 65 yrs) with indwelling urethral catheters. Urine was collected at blocked intervals from 0-2, 2-8, and 8-24 hours and then added together to determine the 8- and 24-hour clearances. The mean 8 hour creatinine clearance was not significantly different from the 24-hour value, whereas the mean 2-hour creatinine clearance was significantly different. The 8 hour value was less biased (2.2 and 10.7 ml/min, respectively) and more precise (11.7 and 25.3 ml/min, respectively) than the 2-hour value. Regardless of age, renal function, serum creatinine level, or diuretic use, the 8-hour value was less biased, usually more precise, and clinically more accurate. Thus it can be used in stable, hospitalized, elderly patients with indwelling catheters to determine degrees of renal impairment and provide optimum drug dosing. PMID- 8469621 TI - Renovascular effects of nonprescription ibuprofen in elderly hypertensive patients with mild renal impairment. AB - To determine the renovascular effects of nonprescription ibuprofen in the maximum labeled over-the-counter (OTC) dosage for 7 days, and to compare these effects with those of two other available OTC analgesics, aspirin and acetaminophen, we evaluated 25 elderly patients with mild thiazide-treated hypertension and mild renal insufficiency. Under double-blind conditions, patients were randomly allocated to one of three treatment groups: ibuprofen 400 mg 3 times/day, aspirin 650 mg 3 times/day, or acetaminophen 650 mg 3 times/day. Blood pressure and indexes of renal function (blood urea nitrogen, creatinine clearance, serum electrolytes) were measured over 7 days in a clinical research center. None of the treatments had a clinically significant effect on blood pressure. Renal function indexes also remained unchanged during all three treatments. We conclude that elderly patients with mild thiazide-treated hypertension and mild renal insufficiency seem not to be at risk of developing additional renal compromise or of having their hypertension control diminished by treatment with these OTC analgesics for 7 days. PMID- 8469622 TI - The effect of isradipine on theophylline pharmacokinetics in healthy volunteers. AB - The effects of isradipine 2.5 mg and 5 mg on the disposition of theophylline were investigated in a placebo-controlled, randomized, three-way, crossover trial. Eleven healthy, nonsmoking men each received a treatment of placebo, and isradipine 2.5 mg and 5 mg every 12 hours for 6 consecutive days. On the morning of day 6, 2 hours after the isradipine dose, theophylline (solution) 5.0 mg/kg was administered orally, and blood samples were collected over 24 hours. A 2-week washout period separated treatment sequences. Plasma samples were analyzed for theophylline using high-performance liquid chromatography. Using a two-way analysis of variance, no significant changes in apparent theophylline clearance were observed between placebo, and isradipine 2.5 and 5 mg (0.815 +/- 0.164, 0.870 +/- 0.212, and 0.827 +/- 0.164 ml/min/kg, respectively; p = 0.136). Similarly, no significant change in volume of distribution was noted. These findings suggest that isradipine at recommended dosages does not impair theophylline metabolism. PMID- 8469623 TI - Ode to beer cans, canoes, house trailers, and Jimmy Buffet: a commentary. PMID- 8469624 TI - Pseudomonas aeruginosa-acquired resistance to imipenem-cilastatin: commentary on clinical implications of antibiotic resistance. PMID- 8469625 TI - Human gene therapy. PMID- 8469626 TI - Congestive heart failure in neonates due to intracranial arteriovenous malformation: endovascular treatment. AB - Newborns with intracranial arteriovenous malformations and congestive heart failure have an extremely poor prognosis. This report describes two infants with intracranial arteriovenous malformations and severe congestive heart failure successfully treated in the newborn period with endovascular embolization. Both infants had immediate improvement in symptoms and both had second embolization procedures performed. Ventriculoperitoneal shunting was necessary in both children because of progressive hydrocephalus. At follow-up of more than 4 years, neither patient has any sign of congestive heart failure, and one is developmentally normal. PMID- 8469627 TI - Familial interruption of the aortic arch. AB - Interruption of the aortic arch (IAA) is an important congenital cardiac malformation occurring in 1.4% of cases with a congenital cardiac malformation. Only two reports have described IAA in siblings, each with type B and an anomalous right subclavian artery. We report the occurrence of IAA type B with an anomalous right subclavian artery in two siblings and their half-sibling, each of whom had additional conotruncal cardiac malformations. Recent evidence suggests that conotruncal cardiac malformations, including IAA type B, are related to abnormalities of neural crest cell migration. Thus, the family reported herein may manifest a syndrome related to alterations in mesenchymal tissue/neural crest cell migration. PMID- 8469628 TI - Seizures due to lidocaine toxicity in a child during cardiac catheterization. AB - A 17-month-old boy developed grand mal seizures secondary to lidocaine toxicity during balloon dilatation of a congenital pulmonary valve stenosis. Lidocaine at 38 mg/kg (nine times the recommended maximum dose of 4.5 mg/kg) was administered during a 90-min period in order to optimize local anesthesia. This resulted in toxic serum lidocaine levels (8.7 mg/L; therapeutic range, 1.5-5 mg/L) at the time of seizures. Caution should be exercised with local anesthetics during invasive cardiac catheterizations. Hypercarbia (which lowers the seizure threshold to local anesthetics) should be avoided and the temptation to exceed the maximum recommended dose resisted. PMID- 8469629 TI - Failure of adenosine to terminate focal atrial tachycardia. AB - Adenosine has proven effectiveness in the diagnosis and treatment of a variety of tachycardias with both normal and widened QRS complexes in children and adults. Its effectiveness is due to its depressant effects on atrioventricular node conduction. Adenosine might also be effective against automatic tachycardia due to spontaneous activation in partially depolarized cells. This report describes a patient presenting with tachycardia with normal QRS complexes. While the adenosine did not restore sinus rhythm, it did disclose the mechanism of the arrhythmia. Since other investigators have reported successful interruption of automatic atrial tachycardia, this case suggests that automatic atrial tachyarrhythmia may be due to more than one mechanism. PMID- 8469630 TI - Pseudohypertension in a child with Williams syndrome. AB - Pseudohypertension has often been reported in elderly subjects, but is an unusual phenomenon in children. We report the case of a 5-year-old child who presented with features of Williams syndrome (characterized by elfin facies, supravalvar aortic stenosis, and peripheral pulmonary artery stenosis). Repeated blood pressure recordings made with appropriately sized blood pressure cuffs were very high, while simultaneous intraarterial blood pressure was normal, confirming the presence of pseudohypertension. This was shown to be caused by excessively thickened arterial vessels. PMID- 8469631 TI - Polysplenia with pulmonary arteriovenous malformations. AB - A patient with polysplenia syndrome, dextrocardia, left atrial isomerism, normal great vessel relationships, and no intracardiac shunts developed progressive cyanosis and clubbing. Pulmonary arteriovenous malformations (PAVMs) were diagnosed by angiography and confirmed by lung biopsy. Superior mesenteric arteriogram revealed hypoplasia of the intrahepatic portal vein branches and a portosystemic shunt. The possible etiologies of PAVMs are discussed. PMID- 8469632 TI - Severe mitral insufficiency in mucopolysaccharidosis type III-B (Sanfilippo syndrome). AB - A 6-year-old girl with mucopolysaccharidosis (MPS) III-B (Sanfilippo syndrome) who developed severe mitral regurgitation and congestive heart failure requiring surgery (valvuloplasty) is reported. One year after surgery the patient remains well, with marked improvement in her physical activity, and without signs of heart failure. This is only the second report of severe mitral regurgitation in MPS III, and is the first report of a successful repair (valvuloplasty) of a dysplastic mitral valve in the MPS. Mitral valvuloplasty should be considered instead of valve replacement in any MPS patient with mitral valve regurgitation requiring surgery. PMID- 8469633 TI - Aortic atresia and tricuspid atresia occurring in complete transposition of the great vessels. AB - A unique case of aortic atresia and tricuspid atresia associated with transposition of the great vessels is described in a newborn infant. The clinical, echocardiographic, and heart catheterization data are presented. The embryological and surgical implications are discussed. PMID- 8469634 TI - Discordance between thallium-201 scintigraphy and coronary angiography in patients with Kawasaki disease: myocardial ischemia with normal coronary angiogram. AB - To assess the usefulness of radionuclide tests in detecting coronary occlusive lesions in children with Kawasaki disease, we compared the results of stress thallium-201 myocardial single photon emission computed tomography with dipyridamole infusion and coronary angiography in 34 patients (19 males and 15 females). Perfusion defects on the stress image only were categorized as transient and were attributed to coronary vascular disease in the presence of redistribution on the delayed image. Others were classified as persistent, due to myocardial damage. Five of the seven children (71%) with severe stenosis on coronary angiography showed persistent and/or transient perfusion defects. However, six of the 11 children (55%) with aneurysms but no obvious stenosis, and four of the 16 children (25%) with normal angiography, showed persistent and/or transient defects. After analyzing 20 individual segments of perfusion defects in the 15 children, six segments (30%) were attributed to the stenosis of supplying coronary arteries, six segments (30%) were related to the coronary aneurysms, and eight segments (40%) were unrelated to any abnormalities on angiography. Thus, significant discordance between the radionuclide and angiographic studies was demonstrated. These results suggest that coronary lesions, as conventionally defined by angiography and supplemented by echocardiography, may not completely identify all Kawasaki patients who may develop myocardial ischemia in the future or who had ischemia in the past. PMID- 8469635 TI - Congenital heart disease in CHARGE association. AB - This study reviews the spectrum of congenital heart disease and associated anomalies in 59 patients with the CHARGE association. We have analyzed our clinical experience in managing the cardiovascular anomalies and have reviewed outcome and risk factors for mortality. This study also highlights problems of cardiac management in children born with multiple system involvement. Twenty patients have died; actuarial survival was 78% at 1 year and 60% at 10 years. In only four of the nonsurvivors could their demise be ascribed to their underlying congenital heart disease. We found the outlook for survival was poor if more than one of the following three features were present; cyanotic cardiac lesions, bilateral posterior choanal atresia, or tracheoesophageal fistula. However, mortality was largely due not to the structural heart or choanal abnormalities, but instead reflected the underlying pharyngeal and laryngeal incoordination which resulted in aspiration of secretions. Furthermore, outcome is likely to be improved if collaboration between specialist surgical teams allows necessary procedures to be performed using the minimum of anesthetics. Examination of both the short- and long-term management of these children has stressed the importance of a multidisciplinary approach to their care. The pattern of cardiac defects was not random; lesions within the Fallot spectrum accounted for 33% of their congenital heart disease. Atrioventricular septal defects were also overrepresented. Not all cardiovascular defects could be explained by hypothesizing a neural crest etiology. PMID- 8469636 TI - Parachute-like sinus venosus remnant: echocardiographic and pathological appearance. AB - A female infant with multiple congenital abnormalities and a right atrial "mass" on echocardiography is reported. Her general condition at birth was poor, and the chest x-ray showed cardiomegaly. Echocardiography demonstrated the usual atrial arrangement and concordant atrioventricular and ventriculoarterial connections with a mobile right atrial mass. Death occurred at 3 days of age and subsequent postmortem examination revealed a hollow, tube-like sinus venosus remnant mobile between right atrium and ventricle with numerous other abnormalities of the heart, including left heart hypoplasia and tubular hypoplasia of the aortic arch. Filling of the sinus venosus remnant with blood had resulted in an echocardiographic appearance suggestive of a right atrial tumor. PMID- 8469637 TI - Transient mitral regurgitation in acute glomerulonephritis. AB - During an epidemic of acute glomerulonephritis (AGN) 15 patients were studied by M-mode, cross-sectional, and Doppler echocardiography. All 15 patients had the classical signs of the disease including hematuria, proteinuria, edema, and consistent laboratory findings. There were 10 boys and five girls with a mean age of 8 years. Ten of the 15 patients had an enlarged left atrium and five of these 10 also had transient mild to moderate mitral regurgitation. In the five patients with mitral regurgitation the ratio of left atrium/aorta was 1.48; in the five patients with an enlarged left atria without evidence of mitral regurgitation the left atrium/aorta ratio was 1.34. All the patients had normal left ventricular dimensions, as well as ejection and shortening fractions. The findings of left atrial enlargement and mitral regurgitation disappeared gradually in all patients within 3 months. There was no correlation between the level of systemic blood pressure and the development of mitral regurgitation. A possible cause for these changes is fluid overload in the oliguric phase of the acute glomerulonephritis. The changes are transient and probably functional. There was no significant mitral valve or left atrial anomaly 3 and 6 months after hospital discharge. PMID- 8469638 TI - Acute rheumatic fever in Saudi Arabia: mild pattern of initial attack. AB - Fifty-one children with the initial attack of acute rheumatic fever (ARF) were studied prospectively to verify the sociodemographic and clinical profile and to compare results with those from other countries. Most children belonged to large families who lived in an urban setting with ready access to medical care. Unlike reports from many developing countries, the clinical manifestations in this study paralleled data from the West and included arthritis in 76% of the cases, carditis in 43%, and chorea in 8%. Among the 22 cases with carditis, 18 had mitral regurgitation, three developed combined mitral and aortic regurgitation, and one had aortic regurgitation. This study demonstrates the mild nature of ARF in Saudi Arabia and supports the concept that climate and geography appear to bear little relationship to the incidence and severity of ARF. PMID- 8469640 TI - [Genital actinomycosis in the women with in situ intrauterine device]. PMID- 8469639 TI - Rare types of aortic arch anomalies. AB - Rare types of aortic arch malformations include isolation of the right or left subclavian arteries in conjunction with a left or right aortic arch respectively. Isolation of the innominate or carotid arteries and an aberrant left innominate artery may exist in association with a right aortic arch. Other anomalies are persistent fifth aortic arch, subclavian artery as the first branch of the aortic arch, pulmonary artery, and ductus arteriosus sling. The angiocardiographic features and embryology of each of these malformations are discussed. PMID- 8469641 TI - [Synchronous occurrence of papillary thyroid cancers in a cyst of the thyroglossal duct in in the thyroid gland]. PMID- 8469642 TI - [Scurvy--500 years after Columbus]. PMID- 8469643 TI - [Osteogenesis imperfecta with hyperplastic callus formation]. PMID- 8469644 TI - [Morris Simmonds and his importance in hypophysis research from the current viewpoint]. PMID- 8469645 TI - [Kaspar Hauser--individual pathologic observations based on autopsy findings]. PMID- 8469646 TI - [Current pathology of the prostate and efferent urinary tract. On the 77th Congress of the German Society of Pathology in Wurzburg 1-5 June 1993]. PMID- 8469647 TI - [Autopsy refusal and reversal of the proof responsibility in the malpractice process]. PMID- 8469648 TI - [Changes in cancer incidence after cholecystectomy, tonsillectomy or appendectomy? Studies in an autopsy sample]. PMID- 8469649 TI - [Morphologic characteristics and differential diagnosis of central mesenchymal chondrosarcoma--an analysis of 15 cases]. PMID- 8469650 TI - [Regenerative nodular hyperplasia of the liver--case reports and comments on diagnosis and differential diagnosis]. PMID- 8469651 TI - [Genetic morphological fatal syndrome. Smith-Lemli-Opitz syndrome]. PMID- 8469652 TI - [Genetic morphological fatal syndromes. The Fryns syndrome]. PMID- 8469653 TI - [Genetic morphological fatal syndromes. The cryptophthalmos syndrome (Fraser syndrome)]. PMID- 8469654 TI - ["Iatrogenic" fatal gas gangrene infection]. AB - The problems associated with lethal gas gangrene infections that arise in connection with medical treatment are described and discussed, based on our own observations and on cases reported in the literature. Special emphasis is placed on questions relating to causality and responsibility. The difficulties encountered in the evaluation of such "iatrogenic" gas gangrene infections are due to the fact that clostridia occur ubiquitously, i.e. that they also reside in the human organism, for instance on the skin. For this reason a positive bacteriological diagnosis of gas gangrene does not necessarily mean that a clinically relevant infection and/or disease state is present at the same time. The implications for morphological practice arising from this situation are discussed, especially with regard to the significance of the intravital, agonal or postmortem bacteriological diagnosis of gas gangrene. Questions concerning the obligation to report such cases when encountered during forensic autopsies are also addressed. PMID- 8469655 TI - [Extrarenal clearance in HIV-infected patients with chronic kidney failure. Experience in a hospital center]. AB - In HIV-infected patients with end-stage renal failure maintenance dialysis raises multiple problems, the most important of these being the quality and duration of life in these patients and the risk of contaminating other HIV negative patients under dialysis and/or members of the medical-nursing staff. In this study the results obtained in 14 patients treated in one single centre over a 5-year period are analyzed. Nine patients (group I) had end-stage renal failure consecutive to HIV-associated nephropathy: 5 died after 2 to 30 months (mean 9.2 +/- 5.2) of dialysis, while 4 patients were alive at the end of the study with a mean follow up of 23.8 +/- 8.8 months (5 to 50). Five patients (group II) had end-stage renal failure consecutive to a nephropathy unrelated to HIV: only 1 female patient died 29 months after she was found to be seropositive; the remaining 4 patients were alive at the end of the study with a mean 47.5 +/- 5.5 months (33 to 58) of follow-up. Ten patients were found to have a less than 8 g/dl Hb anaemia which was corrected in the 4 patients who received recombinant human erythropoietin. Out of the 9 patients treated with zidovudine (300 mg/day) 6 had haematological side-effects. Throughout this study, there was no contamination of HIV negative patients or members of the medical-nursing staff. In these 2 groups, the survival of HIV positive patients dialysed for chronic renal failure seems to have been conditioned by the stage of HIV infection at the time when maintenance dialysis was instituted. PMID- 8469656 TI - [Hyperandrogenism in hirsute and obese women. Effects of a low calorie diet]. AB - To investigate the relationship between overweight and hyperandrogenism, a 1500 kcal/day diet was prescribed for 4 months to 23 hirsute and obese patients. This diet decreased body mass index from 29.9 +/- 4.9 to 27.2 +/- 4.4 kg/m2 (P < 0.008), but had no significant effect on fasting insulin levels (18.9 +/- 14.2 vs. 21.1 +/- 9.6 mlU/l). Weight lost increased significantly (P < 0.008) the plasma concentration of sex-hormone binding-globulin (SHBG) from 21.2 +/- 10.6 to 26.2 +/- 13.5 nmol/l and decreased significantly (P < 0.04) the SHBG-unbound testosterone concentration from 9.3 +/- 6.2 to 7.2 +/- 4.8 ng/dl, without changing the concentrations of the main androgens measured in this study. Moreover, during diet 5 patients in amenorrhea and 8 among 13 patients with irregular menstrual cycle recovered regular menses. We concluded that the control of excess body weight in hirsute women is effective but not sufficient to improve hyperandrogenism. PMID- 8469657 TI - [Azygo-portal disconnection by the abdominal route]. AB - Azygo-portal disconnection by the abdominal route consists of devascularization of the lower oesophagus, cardiac orifice and greater gastric tuberosity by ligation of the varices and section of the oesophagus, combined in every case with truncular vagotomy and gastric bypass. In emergencies the abdominal approach enables the bleeding points to be accurately localized. In the treatment of haemorrhages due to portal hypertension, this technique offers an alternative to porto-caval bypasses when these cannot be performed (thrombosis or portal cavernoma) or when the risk of encephalitis is too high. However, contrary to liver transplantation, it is a palliative technique for cirrhotic patients. PMID- 8469658 TI - [Febrile cervicalgia caused by Streptococcus milleri external pachymeningitis]. PMID- 8469659 TI - [Acute necrotic thyroiditis caused by Candida albicans immediately after acute hemorrhagic rectocolitis]. PMID- 8469660 TI - [Outbreak of trichinosis in Auvergne, revealed by acute respiratory distress]. PMID- 8469661 TI - [Hyperhomocysteinemia, a risk factor of cerebral infarction]. PMID- 8469662 TI - [Paraneoplastic retinopathy (CAR syndrome) revealing prostatic cancer]. PMID- 8469663 TI - [Hodgkin's disease with vertebral localizations. Indication for orthopedic treatment]. PMID- 8469664 TI - [Periprosthetic popliteal abscess caused by Listeria monocytogenes]. PMID- 8469665 TI - [Sclerodermatous cutaneous reaction of graft vs host disease treated with thalidomide]. PMID- 8469666 TI - Sporogony of Theileria sergenti in the salivary glands of the tick vector Haemaphysalis longicornis. AB - Sporogony of Theileria sergenti in the salivary glands of the tick vector Haemaphysalis longicornis was observed by light and transmission electron microscopy. Fission bodies that developed from kinetes were observed as masses (approximately 32 x 15 microns) that occupied half of the acinous cell at 2 days after the infestation of ticks. Parasites possessed an irregular nucleus of low electron density, highly electron-dense granules, and mitochondrion-like bodies in the cytoplasm. Parasites developed into a multinucleate syncytium, increasing in size and complexity. Subsequently, the nuclei of parasites became round and highly electron-dense, and tubelike structures and rhoptries as precursors of the highly electron-dense granules appeared in the cytoplasm. Approximately 40,000 sporozoites arose via radial budding from the syncytium that had developed from kinetes. As in T. parva, no evidence of discrete secondary or tertiary sporoblasts was found in T. sergenti. The sporogony of T. sergenti was extremely similar to that of T. parva. PMID- 8469667 TI - Ultrastructural observations of host-cell invasion by sporozoites of Eimeria papillata in vivo. AB - Scanning and transmission electron microscopy were used to study the invasion of mouse small-intestinal epithelium by sporozoites of Eimeria papillata. Some mice received oocysts by gavage and others received either sporocysts or sporozoites by direct injection into the small intestine. The highest concentration of invaded cells were found in ligated intestinal tissues studied at 5-45 min after the inoculation of sporozoites. Sporozoites actively invaded anterior end first, which resulted in extensive damage to the host cell. Such cells showed disrupted microvilli; protuberances of cytoplasm into the lumen, apparently the result of a disrupted plasma membrane; vacuolization of the cytoplasm; and damage to the mitochondria. These damaged cells were rapidly vacated as the sporozoite moved laterally into one or more adjacent intact host cells without entering the lumen. It is suggested that the host cell initially entered from the lumen becomes so severely traumatized that the parasite of necessity enters an adjacent cell as a prelude to further development. Various aspects of host-cell invasion by coccidia and malarial parasites are reviewed. PMID- 8469668 TI - Hatching of Echinostoma caproni miracidia from eggs derived from adults grown in hamsters and mice. AB - Echinostoma caproni eggs developed fully formed miracidia from hamster-source eggs in 9 days and from mouse-source eggs in 10 days under either light or dark conditions at 27 degrees C. Incubation of egg cultures under constant light resulted in miracidial hatching from hamster-source eggs in 11 days and from mouse-source eggs in 13 days. Exposure to light was essential to trigger hatching, with incandescent light providing more consistent stimulation than fluorescent light. A majority of the miracidia hatched at between 1100 and 1600 hours, indicating a diurnal circadian pattern. Eggs stored in a dark environment for 11 days required 6 days to reach maximal hatching after exposure to light. Eggs stored for 46 and 56 days hatched on the same day of their exposure to light. Miracidia that hatched after 56 days of dark storage exhibited aberrant swimming behavior; those stored in a dark environment for 70 days or longer did not hatch when exposed to light. PMID- 8469669 TI - A new method for isolation of the intraerythrocytic stages of Plasmodium and Babesia from their host cells. AB - A new method for the isolation of intraerythrocytic stages of Plasmodium berghei and Babesia divergens from red blood cells is described. The technique is based on hydrodynamic forces occurring in a flow channel containing a turbulent liquid current, which are capable of rupturing infected erythrocytes and removing their plasma membrane from the parasites' surface. The temperature and the concentration of cells were revealed as factors influencing the hydrodynamic forces. About 90% of the intact and apparently infectious parasites of both species were isolated from the lysed erythrocytes. PMID- 8469670 TI - Further evidence for the occurrence of a distinct strain of Echinococcus granulosus in European pigs. AB - The morphology, adult development and genetic characteristics of Echinococcus granulosus isolated from pigs in Poland were examined and compared with those of other recognised strains of E. granulosus. The isolates were characterised by their distinct morphology, rapid maturation and unique DNA hybridisation profiles. The form of E. granulosus that occurs in European pigs may therefore be a distinct strain that can be separated morphologically and genetically from other strains and that exhibits features of epidemiological significance, including a rapid rate of development in dogs and an apparent low infectivity to humans and domestic ungulates. PMID- 8469671 TI - Requirements for the induction of cross-reactive anti-Trichinella IgE antibodies in mice. AB - Mice primed with Trichinella spiralis or T. pseudospiralis and reinfected with either the homologous or the heterologous species produced high levels of IgE antibodies that cross-reacted with the non-inducing strain in passive cutaneous anaphylaxis assays. Cross-reactive antibodies were not induced by primary infection. Cross-reactivity persisted for more than 6 months following secondary infection or destruction of encysted larvae with mebendazole. Both the prevention of larvi-position by thiabendazole and the interruption of infection using naphthalophos indicated that the presence of the pre-adult stage alone provided sufficient priming for the induction of detectable levels of cross-reactive IgE by subsequent reinfection. These results suggest the existence of two sets of Trichinella allergens, one comprising species-specific major allergens (MAs) and the other comprising minor allergens (mAs) evoking a cross-reactive IgE response that occurs to a detectable extent only when the response to MAs has reached its ceiling. These findings are relevant to the design of experiments investigating the role played by IgE antibodies in protection against reinfection in rodents. PMID- 8469672 TI - Hysterothylacium aduncum (Rudolphi, 1862) infection in cod from the Oslofjord: seasonal occurrence of third- and fourth-stage larvae as well as adult worms. AB - Hysterothylacium aduncum infections in cod from the Oslofjord were followed for 1 year. The recovered worms were grouped according to developmental stage [third stage larvae (L3), fourth-stage larvae (L4) and adult worms] and according to location (in the gut or encapsulated on the viscera). The cod were found to be infected with H. aduncum (all stages lumped) throughout the whole year, with the prevalence approaching 100%. The abundance of the parasites (mean number per fish studied), however, was clearly lowest during the summer months. L3 and L4 recovered from the intestine dominated most of the time but showed a very clear peak during late winter and early spring. L3 recovered from the body cavity was the only stage that showed a clear peak during the summer months. Adult worms, although adult worms were present in very small numbers throughout the year, they tended to peak in May and then again in December and January. Since there did not seem to be a correlation between the accumulation of L3 in the body cavity and the length or age of the fish, the possibility of self-infection whereby the larvae reenter the gut and continue to develop into L4 and then into adults, is discussed. PMID- 8469673 TI - Failure of treatment with alpha-difluoromethylornithine against secondary multilocular echinococcosis in mice. AB - In AKR/J mice inoculated intraperitoneally with protoscoleces of Echinococcus multilocularis, the oral administration of alpha-difluoromethylornithine (DFMO) in drinking water had no obvious effect on the development of hydatid cysts. The DFMO treatment also caused no apparent depletion of three major polyamines (putrescine, spermidine, and spermine) in the cysts, although a slight reduction in the putrescine level was detected. The failure of DFMO treatment to reduce the growth of cysts in mice may result from the absence of ornithine decarboxylase in the parasite. PMID- 8469674 TI - Secretion of an Eimeria tenella sporozoite antigen during host-cell invasion: visualization of the parasitophorous vacuole membrane and parasitophorous duct like structures. PMID- 8469675 TI - A cDNA putatively encoding the Pc90 erythrocyte membrane antigen of Plasmodium chabaudi. PMID- 8469677 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 8469676 TI - Trichinella spiralis--characterization of circulating and immune-complex associated antigens. PMID- 8469678 TI - Prostaglandin and portal hypertension. PMID- 8469679 TI - Exaggerated splanchnic PGI2 release following acute hemorrhage is due to new protein synthesis. AB - The effect of cycloheximide on increased splanchnic prostacyclin release following acute hemorrhage was studied in the rat. Male Sprague-Dawley rats were anesthetized and subjected to acute hemorrhage to 30 mm Hg for 30 min (shock) or sham shock. The superior mesenteric artery was cannulated and removed with its end organ intestine (SV + SI preparation) and perfused in vitro with oxygenated Krebs-Henseleit buffer. Cycloheximide was infused in half of the sham and acute hemorrhage SV + SI preparations at 50 micrograms/ml. Venous effluent from all groups were analyzed for prostanoid release by radioimmunoassay. The SV + SI released 10-fold more 6-keto-prostaglandin (PG) F1 alpha than PGE2 and thromboxane. Acute hemorrhage increased SV + SI release of 6-keto-PGF1 alpha 3 fold compared to sham. Cycloheximide abolished the increased 6-keto-PGF1 alpha following acute hemorrhage but not the basal release in the sham group. Indomethacin decreased PG synthesis in all groups by 90%. Sham PG release was dependent on a stable pool of cyclooxygenase with a long half-life and was not affected by cycloheximide treatment. Acute hemorrhage stimulated a rapid induction of enzymes (cyclooxygenase, prostacyclin synthase) responsible for prostacyclin synthesis and release which were dependent on de novo protein synthesis. PMID- 8469680 TI - Thromboxane receptor antagonism and synthase inhibition in cerebral ischemia. AB - Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that may suppress regional cerebral blood flow (rCBF) during postischemic hypoperfusion. This study was undertaken to determine if rCBF could be elevated by postischemic treatment with a TXA2 receptor antagonist, SQ29,548, given alone or in combination with 1 benzylimidazole (1-BI), a thromboxane synthase inhibitor. Wistar rats were subjected to 30 min of reversible forebrain ischemia and treated with SQ29,548 or an SQ29,548/1-BI combination during 60 min of reperfusion. Cerebral TXB2, the stable metabolite of TXA2, was 1.33 +/- 0.91 ng mg brain protein-1 in animals treated with SQ29,548 and exposed to ischemia, compared to 1.15 +/- 0.32 in ischemic controls (p = NS). Administration of SQ29,548/20 mg kg-1 1-BI reduced cerebral TXB2 to 0.20 +/- 0.25 (p < or = 0.01). Regional CBF was depressed significantly in ischemic controls compared to sham-ischemic animals (p < or = 0.01 in all regions except for p < or = 0.05 in diencephalon) and was not altered by treatment with SQ29,548. Rats given the SQ29,548/1-BI combination showed an overall increase in rCBF that did not reach statistical significance when compared to ischemic controls. However, rCBF in hippocampus and diencephalon of animals given the drug combination was significantly greater than in rats treated with SQ29,548 alone (p < or = 0.05). PMID- 8469681 TI - Effects of guinea-pig endometrial proteins on phospholipase A2 activity and prostaglandin synthesis. AB - The major protein secreted by Day-15 guinea-pig endometrium cultured for 24 h had a molecular weight of 68.3 kDa on SDS-PAGE. This protein had no effects on phospholipase (PL) A2 activity in vitro and prostaglandin (PG) production by Day 7 guinea-pig endometrium in culture. Following purification, proteins present in fractions F1, F2, F7, F7:2 and F7:3 (which comprised < 15% of the total amount protein secreted) increased PLA2 activity in vitro. The major proteins in F7:2 had molecular weights of 13.9 and 15.6 kDa on SDS-PAGE, but they had no effect on endometrial PG synthesis in the concentration used (20 mg/ml). Unpurified endometrial secreted proteins had no effect on PLA2 activity, but stimulated endometrial PG synthesis. This stimulation was lost following purification of the proteins, and may have been due to a large amount of contaminating serum albumin. The mechanism by which oestradiol acting on a progesterone-primed guinea-pig uterus stimulates endometrial PGF2 alpha synthesis by a process which is dependent upon increased endometrial protein synthesis still remains obscure. PMID- 8469682 TI - Indomethacin-induced gastrointestinal ulcers in rats: effects of dietary fatty acids and endotoxin. AB - The purpose of this study was to determine how dietary n-3 and n-6 polyunsaturated fatty acids (PUFA) affected the gastrointestinal response to lipopolysaccharide (LPS) and indomethacin (INDO) in the rat. Rats were fed diets containing 12.5% linseed oil (LO-enriched in short-chain n-3 PUFA) or corn oil (CO-enriched in n-6 PUFA). After 30 days on the diets, rats were given one of three treatments 1:10 mg/kg O55:B5 Escherichia coli LPS intraperitoneally (i.p.), 2:25 mg/kg INDO subcutaneously (s.c.), 3: a combination of 10 mg/kg i.p. LPS and 25 mg/kg (s.c.) INDO given 30 min before LPS. 20 h after challenge, rats were given an intravenous injection of Monastral Blue B to stain ulcer areas in the gastrointestinal tract. Lipopolysaccharide did not result in any Monastral Blue B vascular leakage in the gastrointestinal tract. Rats on the LO diet had significantly increased stomach and intestinal ulcers compared to CO fed rats. When rats were challenged with LPS and INDO, the LPS almost completely eliminated small intestinal ulcers, but enhanced ulcer development in the stomach. PMID- 8469683 TI - The effects of a cysteinyl leukotriene antagonist (ONO-1078) on antigen-induced responses in allergic sheep. AB - The cysteinyl leukotrienes (LTC4/D4/E4) are putative mediators of asthma. In this study we used sheep allergic to Ascaris suum antigen to examine the effects of a novel orally active cysteinyl LT antagonist, ONO-1078, on antigen-induced early and late responses, airway inflammation, post challenge (24 h) airway hyperresponsiveness (AHR) and mucociliary clearance. Airway responses to antigen were determined by measuring specific lung resistance (SRL) before and for 8 h after challenge, bronchoalveolar lavage (BAL) was used to estimate airway inflammation, and airway responsiveness was measured by determining the carbachol dose that increased SRL by 400% (PC400). We also used a radiographic technique to measure the antigen-induced change in tracheal mucus velocity (TMV), a marker of mucociliary clearance. In two trials separated by at least 21 days, sheep were treated once with ONO-1078 (30 mg/kg, p.o.) and once with placebo (0.5% methylcellulose), 2 h before and 4 h after antigen challenge. Treatment with ONO 1078 (n = 7) provided 40% protection (p < 0.10) against the peak early increase in SRL, resulted in a more rapid reversal of the early response, and provided 96% protection against the peak late (6-8 h) increase in SRL. ONO-1078 also inhibited the AHR 24 h after challenge. In the drug trial, PC400 was unchanged as compared to pre-challenge, whereas in the placebo trial, PC400 was decreased 1.4-fold (p < 0.05). Treatment however, did not affect BAL cell numbers or differential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469684 TI - Arachidonic acid supplementation dose-dependently reverses the effects of a butter-enriched diet in rats. AB - Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks which was supplemented orally with 9, 18, 36, or 72 mg/day of ethyl arachidonate for a further 2 weeks. The control group of animals were fed a 5% fat diet for 4 weeks. Aortic prostacyclin (PGI2) production, platelet aggregation and thromboxane A2 (TXA2) production and plasma and aortic phospholipid (PL) fatty acids were measured. 50% butter-feeding resulted in a significant reduction in aortic PGI2 production and collagen-induced platelet aggregation and TXA2 production. These changes were accompanied by a reduction in plasma and aortic PL arachidonic acid levels and an increase in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), 5,8,11-eicosatrienoic acid (ETA) and dihomo-gamma linolenic acid (DGLA). These changes in prostanoid production, platelet aggregation and PL fatty acid composition were dose-dependently reversed by the daily oral administration of ethyl arachidonate (9, 18, 36, or 72 mg). The threshold dose being as little as 9 mg of ethyl arachidonate/rat/day for reversal of PL fatty acid composition, collagen-induced platelet aggregation and TXA2 production, and 18 mg of ethyl arachidonate/rat/day for reversal of aortic PGI2 production. Full reversal was seen generally with 36 or 72 mg of ethyl arachidonate/rat/day. The data highlight the responsiveness of tissue eicosanoid production to small quantities (ppm) of dietary eicosanoid precursors. PMID- 8469685 TI - Importance of secondary TXA2 release in mediating of endothelin-1 induced bronchoconstriction and vasopressin in the guinea-pig. AB - The i.v. bolus application of 1 nmol/kg endothelin-1 (ET-1) in anaesthetized and ventilated guinea-pigs caused an increase in mean arterial blood pressure (BP) and a bronchoconstriction. Both have been reduced or abolished by COX inhibition (ASA) or substances specifically reducing the thromboxane A2 (TXA2) generation (HOE 944) or receptor binding (BM 13177). The significant increase in TXB2 concentrations in plasma and bronchoalveolar lavage (BAL) after ET-1 challenge (15-fold and 4-fold, respectively) have been reduced or abolished by ASA as well as HOE 944 and not altered by BM 13177. PMID- 8469686 TI - Effects of striatal or accumbens lesions on the amphetamine-induced abolition of latent inhibition. AB - In this study, we tested the effects of nucleus accumbens or corpus striatum lesions on the abolition of latent inhibition induced by d-amphetamine. In the latent inhibition paradigm, animals learn to ignore a repeatedly presented nonreinforced stimulus. In this paradigm, the repeated nonreinforced preexposure to a stimulus retards subsequent conditioning to that stimulus. Pharmacological manipulations that enhance the dopaminergic function (e.g., d-amphetamine) abolish this ability to ignore an irrelevant stimulus. Previous studies have revealed a major role of the nucleus accumbens in the d-amphetamine-induced abolition of latent inhibition because intraacumbens injections of the drug mimic its systemic effects. The results of this study, however, revealed a significant increase in the disruption of latent inhibition by d-amphetamine between corpus striatum-lesioned and sham-operated rats, but a marginal difference between nucleus accumbens lesioned and sham-operated rats, which had been preexposed to the stimulus. These findings indicate that the corpus striatum plays also a major role in the disruption of latent inhibition by d-amphetamine. It seems, therefore, that the nucleus accumbens and corpus striatum may represent a functionally common system regarding the expression of latent inhibition, although different experimental manipulation can favor the one structure over the other, reflecting probably their complex function. PMID- 8469687 TI - Opioid regulation of parental behavior in juvenile rats. AB - When exposed to young rats for a period of days, juvenile rats will respond with full parental behavior (FPB: retrieval and grouping of, and crouching over, pups). Because the parental behavior of juveniles is so robust, and because opiates have been shown to be involved in the regulation of parental behavior in adult animals, we examined morphine's ability to disrupt the display of parental behavior in the juvenile animal. In Experiment 1, 25-day-old males and females were administered one of three injection regimens of morphine (MOR), saline (SAL), or naloxone (NAL)--[MOR (5.0 mg/kg) + SAL; MOR + NAL (0.5 mg/kg); or SAL + SAL]--and 1 h later were exposed to three 1- to 6-day-old neonates. Behavior was scored over a 60-min period and animals were considered parental if they responded with FPB for 2 consecutive testing days. Whereas the SAL + SAL and MOR + NAL were not different, MOR + SAL virtually failed to respond to young over a 10-day period. Experiment 2 exposed juveniles to young for a period of days until they displayed 2 consecutive days of FPB. Next, separate groups of juveniles were treated with the same regimen as above. Again, SAL + SAL and MOR + NAL responded rapidly to young, whereas MOR + SAL did not. These data suggest that the display of parental behavior, both its onset (Experiment 1) and maintenance (Experiment 2), appears to be regulated by opiates. PMID- 8469688 TI - Discriminative stimulus properties of NIK-247 and tetrahydroaminoacridine, centrally active cholinesterase inhibitors, in rats. AB - The discriminative stimulus effect of the novel centrally active cholinesterase inhibitor, NIK-247, was investigated in rats and compared with that of tetrahydroaminoacridine (THA). Rats were trained to discriminate either 10 mg/kg NIK-247 or 1.8 mg/kg THA from saline in a two-lever food-reinforced procedure. The stimulus effect of NIK-247 was substituted for by the cholinesterase inhibitors, THA and physostigmine. The THA stimulus was substituted for by NIK 247 and physostigmine. The muscarinic receptor agonist arecoline substituted for the NIK-247 and THA stimuli. Both stimulus effects of NIK-247 and THA were blocked by the muscarinic antagonist scopolamine. The dopaminergic-activating drugs amantadine and lisuride substituted for the stimulus effects of NIK-247 and THA. However, neither the NIK-247 nor the THA stimulus was antagonized by the dopamine antagonists haloperidol, SCH 23390, and sulpiride. These results suggest that the discriminative stimulus effects of NIK-247 and THA are mediated by muscarinic receptors, and that the dopaminergic activity resulting from cholinergic activation may account for some part of both stimuli. PMID- 8469689 TI - Lack of synergistic feeding enhancement by systemic clonidine and 8-OH-DPAT. AB - To expand on recent suggestions that brain alpha 2-adrenergic and serotonergic systems may interact in their controls over feeding, three experiments were conducted to determine if combining clonidine and 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT) injections subcutaneously might produce exponential feeding enhancements greater than responses elicited by either agent alone. Ad lib fed adult male rats were tested in 2 x 2 drug designs in all studies. In Experiment 1, 30 micrograms/kg clonidine reliably enhanced feeding over a 6-hr test period. However, 250 micrograms/kg 8-OH-DPAT showed no signs of enhancing this response, but instead seemed to impede it as determined by analyses of cumulative intake curves. In Experiment 2, either 10 micrograms/kg clonidine or 250 micrograms/kg 8-OH-DPAT reliably enhanced 6-h interval intakes, but their combination again failed to synergize other than to interact with time in suppressing intake. To determine if feeding synergy might occur if subthreshold doses of each agent were combined, Experiment 3 tested 1 microgram/kg clonidine and 15 micrograms/kg 8-OH-DPAT in 4-h feeding tests. Neither agent alone elicited reliable feeding as planned, but their combination also failed to stimulate feeding. These findings, combined with other recent work, do not support the possibility that previously demonstrated interactions between brain alpha 2-adrenergic and serotonergic systems extend to circumstances wherein enhancements of the former combined with suppressions of the latter might underly robust overeating responses. PMID- 8469690 TI - Postnatal handling, perinatal flumazenil, and adult behavior of the Roman rat lines. AB - The effect of infantile handling stimulation and/or perinatal flumazenil (Ro 15 1788; a benzodiazepine receptor antagonist; 3.7 mg/kg/day) administration on exploratory and emotional-related behavior was investigated using adult females from the Roman high- and low-avoidance (RHA/Verh and RLA/Verh) lines. When rats (6 months old) were exposed to a hexagonal tunnel maze including an illuminated central arena, it was found that RHA/Verh rats were more active, explored more maze area, showed more outward preference, and more frequently entered the illuminated center than RLA/Verh rats. In addition, postnatal stimulation decreased emotional-related behavior in both lines of rats, as expressed by increased entry into, and time spent in, the central arena. Perinatal flumazenil treatment decreased entry into the maze central arena in both rat lines but this effect was counteracted by postnatal (handling) stimulation. Thus, the present study extends to adult RHA/Verh and RLA/Verh rats the positive long-lasting effects of postnatal handling and shows postnatal handling x flumazenil interactions in some behavioral parameters related to the pattern of exploration and exploratory efficiency. PMID- 8469691 TI - Effects of chronic treatment with two selective 5-HT2 antagonists on sleep in the rat. AB - The effect of chronic administration of 2(2-dimethylaminoethylthio)-3 phenylquinoline (ICI-169,369) and 2(2-dimethylamino-2-methylpropylthio)-3 phenylquinoline (ICI-170,809), two selective 5-HT2 antagonists, on sleep was studied in rats. As previously shown, the acute effect of ICI-170,809 was to increase latency to rapid eye movement sleep (REMS), decrease the number of REM periods (REMPs), suppress the cumulative amount of REMS over 12 h, and increase the duration of REMPs in the first 6 h, while having no effect on non-REM sleep (NREMS). Administration of ICI-169,369 had similar effects except no change was seen in the duration of REMPs and cumulative REMS was suppressed for 24 h. When given 2 x daily for 5 days, tolerance to the REMS suppressant effects developed in both drugs. After discontinuation of treatment, a REMS rebound occurred after ICI-170,809, but not ICI-169,369. No significant effect on NREMS was seen after administration of ICI-170,809, whereas ICI-169,369 lowered 24-h cumulative NREMS on the fifth day of administration. PMID- 8469692 TI - Effect of age and strain on working memory in mice as measured by win-shift paradigm. AB - Working memory is disrupted in Alzheimer's disease and stroke; therefore, any therapeutic drug should restore deficits in working memory. The win-shift foraging paradigm has been demonstrated to be a model of working memory in rats. In the present study, this paradigm was adapted to mice because of the greater ease and economy of testing potential drugs in mice and the wider availability of strains of aged mice with naturally occurring working memory deficits. This study has demonstrated strain differences in the working memory trace and that age induces a deficit that can be detected at 11 months of age in mice. Tacrine and physostigmine enhance the memory trace in normal mice and physostigmine can reverse age-induced working memory deficits in subjects with mild and moderate deficits but not in subjects with severe deficits. PMID- 8469693 TI - Effects of sublethal doses of ionizing radiation on repeated acquisition in rats. AB - To extend previous research on the effects of ionizing radiation on learning, dose-effect data with 60Co gamma-rays were collected for individual rats responding under a repeated-acquisition procedure. Under this procedure, subjects acquired a different three-response chain each session by responding (nose push) on one of three transilluminated response keys in the presence of each of three sequentially ordered colors. The response chain was maintained under a second order fixed ratio (FR) 2 schedule of food presentation. An error produced a 5-s timeout but did not reset the three-response chain. Acquisition of each response chain was defined by a decrease in errors as the session progressed (i.e., within session error reduction). Each session ended after 200 reinforcements or 90 min, whichever occurred first. When day-to-day acquisition for all four subjects reached a steady state, the effects of three or four doses of gamma-rays were assessed. In general, radiation doses of 1, 3, 4.5, and 8 Gy of gamma radiation delivered at a dose rate of 2.5 Gy/min produced a dose-dependent decrease in the overall response rate for 24-72 h after exposure in all four subjects. Radiation exposure also produced an increase in percent errors but only at doses that substantially decreased overall rate of responding. Unlike the effects on response rate, which were relatively consistent over a 72-h period, the effects on accuracy were greater at 72 h than at 24 h in three of four subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469694 TI - Comparison of the effects of scopolamine and methylscopolamine on the performance of a fixed-ratio discrimination in squirrel monkeys. AB - In the presence of a stimulus behind the center key, squirrel monkeys were required to complete one of two fixed ratios (FRs) on the center key (FR 30 or FR 25). Completion of the ratio turned off the center-key stimulus and produced a stimulus behind each of the two side keys. If the completed ratio was high (e.g., FR 30), a response on the left key produced a food pellet. If the ratio was low (e.g., FR 25) a response on the right key produced food. Errors produced a brief timeout. Dose-effect curves for scopolamine (0.001-0.18 mg/kg) and methscopolamine (0.0032-5.6 mg/kg) were determined under a FR 30 vs. FR 25 discrimination, which controlled both moderate levels of accuracy and high rates of responding. Scopolamine produced a dose-related decrease in overall response rates and increase in percent errors. Methscopolamine decreased response rates and increased percent errors in a dose-related manner much like scopolamine. However, scopolamine was found to be about 10 times more potent on a mg/kg basis than methscopolamine. Scopolamine is in general considered to be centrally acting due in part to its lipid solubility. The results from these studies suggest that methscopolamine, in general considered to be peripherally acting, may also cross the squirrel monkey blood-brain barrier at high doses and produce behavioral effects comparable to those of scopolamine. PMID- 8469695 TI - Enhanced acquisition of reversal training in a spatial learning task in rats treated with chronic nimodipine. AB - Nimodipine levels were measured in blood and brain of rats implanted SC with sustained-release pellets of nimodipine (0, 10, 20, or 40 mg). Dose-dependent levels of nimodipine were detected in both plasma and brain. These results indicated the possible usefulness of these pellets in behavioral studies where long-term treatment is required. Therefore, the effects of chronic nimodipine, using 40-mg pellets, were examined on the performance of young, middle-aged, and aged rats in the Morris water maze. Following implantation of either nimodipine or placebo pellets, rats were trained for 6 days (three sessions/day) followed by 6 days of reversal training. During both initial and reversal training, every sixth trial was a probe trial. During initial training, there were clear age related acquisition deficits in place training, with no effects of chronic nimodipine. Nimodipine did, however, enhance performance of rats during the first and second probe trials of reversal training. Time spent in the training quadrant by nimodipine-treated rats was approximately 30% longer on the first reversal probe and 35% longer on the second reversal probe than time spent in this quadrant by placebo-treated animals. These results indicate that chronic nimodipine enhances the performance of normal animals in reversal training on a spatial learning task. PMID- 8469696 TI - Pharmacokinetics of nordiazepam in physical dependence and precipitated abstinence in dogs. AB - Previous studies suggested that the extensive accumulation of benzodiazepines is an important factor in the induction of physical dependence. The mechanistic basis for accumulation of nordiazepam (ND) and its metabolite, oxazepam (OX), have been examined in crossover studies in drug-naive and in ND-dependent dogs that exhibited a flumazenil-precipitated abstinence syndrome. ND and parent OX have similar pharmacokinetic profiles. Steady-state plasma levels of ND and OX cannot be predicted from single-dose pharmacokinetics. Reduced plasma clearance of ND and altered plasma protein binding were observed in dogs physically dependent upon ND. The benzodiazepine antagonist, flumazenil, significantly reduces steady-state plasma levels of total and free ND. PMID- 8469697 TI - Effects of NBM lesions with two neurotoxins on spatial memory and autoshaping. AB - Four groups of Wistar rats received either vehicle, quisqualate, or one of two different ibotenic acid infusions into the basal forebrain. Following recovery from surgery, all rats were tested in three distinct behavioral paradigms: the Battig radial arm maze, the Barnes circular platform, and autoshaping in an operant chamber. The results showed that the size and site of the ibotenic acid lesion had a profound effect on acquisition performance in some, but not all, procedures. Performance in the Battig maze and acquisition of a food-rewarded lever press were in particular disrupted by ibotenic acid lesions. The severity of the reduction in cortical choline acetyltransferase (ChAT) did not correlate with performance in the tests. Quisqualate produced the largest reduction in ChAT levels but had no significant effect on performance in any of the three procedures used. Anatomic analysis revealed severe nonspecific damage to the striatum following ibotenic acid that was more pronounced in the group receiving a highly concentrated solution of ibotenic acid as compared to rats infused with a greater volume but less concentrated solution of the neurotoxin. Striatal damage was much less severe following quisqualic acid infusions. However, both types of neurotoxins produced equivalent nonspecific degeneration of the reticular thalamic nucleus. These data confirm reports that nonspecific damage appears to define the severity of ibotenic acid lesions on subsequent behavioral performance. PMID- 8469698 TI - Role of nicotine dose and sensory cues in the regulation of smoke intake. AB - We investigated the role of nicotine dose and sensory cues in the regulation of ad lib smoke intake. The smoking behavior of 12 adult male smokers was assessed in three conditions, presenting either high-nicotine cigarette smoke (high nicotine, high sensory), diluted cigarette smoke (low nicotine, low sensory), or an aerosol containing cigarette smoke constituents suspended in solution, which was low in nicotine, yet high in sensory impact. Subjects showed marked compensatory increases in smoking with the dilute smoke conditions, whereas they puffed and inhaled the aerosol to a similar extent as the high-nicotine cigarette. Thus, subjects regulated their smoking behavior to equate sensory intensity rather than nicotine intake. Moreover, the aerosol and high-nicotine cigarette conditions lowered craving to a greater degree than the dilute smoke condition. Other mood indices, such as arousal and negative affect, were more effectively relieved by the high-nicotine dose condition. These results highlight the importance of sensory cues in the regulation of smoke intake and modulation of craving and suggest the clinical application of techniques for providing relief of cigarette craving during smoking cessation. PMID- 8469699 TI - Muscarinic and nicotinic influences on masculine sexual behavior in rats: effects of oxotremorine, scopolamine, and nicotine. AB - In this study, the role of cholinergic systems in the regulation of male sexual behavior was analyzed by different approaches. Both muscarinic agonists and antagonists, as well as a nicotine agonist, were administered to sexually experienced male rats. In Experiment 1, oxotremorine (OXO), a muscarinic agonist, decreased the intromission frequency and ejaculatory latency in a dose-dependent way. Moreover, an increase in ejaculatory frequency was observed. In Experiment 2, the muscarinic antagonist scopolamine (SCO) produced a dose-related impairment of sexual behavior, decreasing the percentage of sexually active males. The smaller doses of SCO delayed the initiation of sexual behavior and decreased ejaculatory frequency. In an attempt to analyze the effect of muscarinic supersensitivity on sexual behavior, in Experiment 3 a long-term blockade of muscarinic receptors (SCO for 17 days) was followed by OXO administration. Animals displayed a significant increase of mount frequency, which results in the decrease of both the hit rate and ejaculatory frequency. In Experiment 4, six doses of nicotine were acutely administered. Only the higher doses (0.4, 0.8, and 1.6 mg/kg) induced a decrease in intromission frequency, although no significant differences were found in any other parameter. These results strongly suggest that cholinergic participation in masculine sexual behavior regulation is mediated mainly through muscarinic system. PMID- 8469700 TI - Morphine-induced feeding: a comparison of the Lewis and Fischer 344 inbred rat strains. AB - Rats of the Lewis inbred strain have been shown to self-administer more morphine than rats of the inbred Fischer 344 (F344) strain. Because morphine reward and opioid-induced feeding may involve a common mechanism, we measured whether these strains also differ in their feeding response to morphine. In Experiment 1, rats were maintained on powdered rat chow and given SC injections of morphine sulfate (1, 3, and 10 mg/kg) and saline; all rats were tested with all doses. Food intake was measured 2, 4, and 6 h after injection. In Experiment 2, rats were given a choice of two diets: a fat/protein diet and a carbohydrate/protein diet. Feeding responses to morphine were measured in a manner identical to that in Experiment 1. In both experiments, the feeding response to morphine was greater in Lewis rats than in F344 rats. To determine whether these responses might be explained by differences in the levels of morphine achieved in the blood or brain, rats of each strain were given SC injections of morphine sulfate (3 mg/kg) and sacrificed either 30 min or 3 h after injection. Serum and brain morphine levels were determined by radioimmunoassay. Lewis rats had significantly less brain morphine than F344 rats at 30 min; they did not differ in morphine content at 3 h. Serum levels were similar at 30 min; at 3 h, F344 rats had slightly lower levels than Lewis rats. Thus, differences in tissue levels cannot readily explain the differences in feeding responses to morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469701 TI - Further characterization of the behavioral effects of peripherally administered corticotropin-releasing factor in guinea pigs. AB - Guinea pig pups were either not injected (NI) or given SC injection of either saline vehicle (SAL) or 14 micrograms of corticotropin-releasing factor (CRF). In an isolation test, mean number of vocalizations and several measures of locomotor activity were markedly lower for CRF pups than for NI or SAL controls. CRF pups defecated less than did SAL pups. No differences were found among conditions for self-grooming. Behavioral freezing was shown by only two pups in the entire study. Significantly more CRF pups displayed piloerection, eye-closing, and a characteristic crouched stance than did controls. In a defensive withdrawal test, no differences among conditions were found for the proportion of pups entering a darkened chamber or for the latency to enter the chamber; however, CRF pups entered the chamber significantly fewer times during the 60-min test than did controls. There were no differences among conditions in the distance swum or number of turns made in a forced-swim test. These results replicate our earlier findings that peripheral injection of CRF suppresses vocalizing and a measure of locomotor activity in isolated guinea pig pups and identifies a number of additional behavioral effects. Of central interest here, the results indicate that the suppression of vocalizing and locomotion during isolation is not due to an increase in competing stress-related behavior or to diminished motor capacity. PMID- 8469702 TI - Ethanol consumption following acute fenfluramine, fluoxetine, and dietary tryptophan. AB - Male Sprague-Dawley rats fed a commercial diet with or without tryptophan supplementation (0.5% L-TRP) were treated with single IP injections of fenfluramine or fluoxetine. Rats had been water deprived prior to injection and food was removed during the period of fluid availability. They were offered, following drug or saline injection, water, a 5% ethanol solution, or an isocaloric sucrose solution (8.75%) for 1 h. Fenfluramine injection significantly reduced intake of all fluids, but its effect on ethanol was significantly greater than for water or sucrose solutions. Fluoxetine suppressed water and ethanol intake but not that of sucrose; the reduction in ethanol intake was significantly greater than for water. Ingestion of the tryptophan-supplemented diet in the absence of any drug treatment had no effect on fluid intake. However, the tryptophan supplementation significantly enhanced the reduction in ethanol intake induced by fenfluramine and fluoxetine. It appears that both fenfluramine and fluoxetine decrease ethanol intake more so than that of water or sucrose and that this effect is exacerbated by tryptophan supplementation. PMID- 8469703 TI - Prenatal exposure to morphine or naloxone intensifies morphine dependence at maturity. AB - Pregnant rats were SC injected with physiological saline (control) or 10 mg/kg morphine (morphine group) or 2 mg/kg naloxone (naloxone group) three times daily during the last 5 days of gestation. Three weeks after birth, male young rats of each group were taken and placed in separate cages. When their body weight reached 130-150 g, 10 rats from control, morphine, and naloxone groups were SC implanted with two pellets containing 75 mg morphine base (total 150 mg). Three days following implantation, rats were IP given 2 mg/kg naloxone for precipitated abstinence syndrome. Immediately after naloxone injection, rats were strictly observed for 15 min and jumping, wet-dog shakes, teeth-chattering, diarrhoea, defecation, and ptosis counted or rated. All abstinence syndrome signs were significantly higher in the morphine or naloxone group than in control. On the basis of the previous experimental findings supporting the idea that opiate physical dependence is related to the binding of opiate, possibly other than their own, to NMDA receptors and the upregulation and/or supersensitivity associated with the binding, the intensification of morphine dependence has been attributed to the long-lasting NMDA receptor upregulation and/or supersensitivity. PMID- 8469704 TI - Effects of harmane (1-methyl-beta-carboline) on neurons in the nucleus accumbens of the rat. AB - Harmane, a beta-carboline alkaloid reported to exert locomotor and psychoactive effects, is found in certain plants and also has been shown to exist in the mammalian brain as an endogenous substance. In this study, the effects of locally perfused harmane were examined on spontaneous neuronal activity in the nucleus accumbens of urethane-anesthetized rats. Extracellular single-unit recording, coupled with push-pull perfusion, enabled the discrimination of specific, dose related effects of harmane across a wide concentration range. At lower concentrations (10(-9)-10(-11) M), excitation prevailed, while at higher concentrations (10(-8)-10(-6) M) depression was most pronounced. These findings suggest a neuromodulatory role for harmane in the forebrain reward system. PMID- 8469705 TI - Behavioral effects of long-term administration of an anabolic steroid in intact and castrated male Wistar rats. AB - Once a week, intact and castrated male Wistar rats were intramuscularly injected with a 0.2 ml suspension of either 0, 10, or 50 mg nandrolone decanoate in cottonseed oil, for 8 consecutive weeks. After the sixth injection, locomotor activity was measured in an open-field and the acquisition of lever press behavior was assessed in an autoshaping procedure. Subsequently, all subjects were exposed to four sessions of continuous reinforcement prior to one session in which the effects of steroid administration on extinction were assessed. Locomotor activity decreased for all groups of rats with continued exposure to the open-field, differences between groups were not observed. Rats treated with the highest dose of nandrolone decanoate spent more time in the margin of the open-field. There were no significant differences between groups on any of the learning measures. Long-term, high-dose steroid administration in conjunction with mild food deprivation inhibited growth in intact and castrated rats, while low dose administration affected body weight in intact rats only. Steroid administration resulted in heavier and enlarged kidneys and lighter testes as well. These results suggest that the administration of anabolic steroids not only produces observable physiological changes, but that it may also affect spontaneous behavior. The failure to find differences in learning indices may have been a function of the particular paradigms used in the present experiment. PMID- 8469706 TI - Enhanced learning following a single, acute dose of MDA. AB - The behavioral effects of a single, acute dose of methylenedioxyamphetamine (MDA) were assessed using the rabbit nictitating membrane (NM) preparation. Acquisition of the classically conditioned NM response was carried out in a single session under MDA at doses of 10 and 20 mumol/kg (1.79 and 3.58 mg/kg, respectively) and retention was assessed during a drug-free state 48 h later. In agreement with previous reports, MDA at a dose of 10 mumol/kg enhanced acquisition of the conditioned NM response and learning was retained in the nondrug state. However, MDA at a dose of 20 mumol/kg failed to affect either acquisition or retention. In further agreement with previous reports, MDA at 10 mumol/kg facilitated the amplitude of the unconditioned response during unpaired stimulus presentations. It is suggested that this enhanced motor response may be due to enhanced neural transmission in the afferent limb of the unconditioned reflex arc. PMID- 8469707 TI - Technique for the continuous infusion of high doses of cocaine by osmotic minipump. AB - The present article describes a procedure for modifying osmotic minipumps to avoid the local, toxic, necrotic effects of high concentrations of drug at the exit portal during the chronic, continuous infusion of cocaine. The present procedure eliminates the occurrence of necrotic skin lesions otherwise produced by SC administration of cocaine and/or other vasoconstrictive agents. The method of administration will therefore be useful for administration of other chronic drug regimens. PMID- 8469708 TI - Ethosuximide suppresses seizures and lethality induced by picrotoxin in developing rats. AB - The action of ethosuximide (125 or 250 mg/kg, IP) against picrotoxin-induced seizures (3-6 mg/kg, IP) was assessed in rats 12, 18, 25, and 90 days old. In 18 day-old and older controls, picrotoxin regularly elicited clonic seizures; tonic clonic seizures were induced in all age categories with high consequent mortality. Only the higher dose of ethosuximide (250 mg/kg) increased the latency of clonic seizures in 18- and 25-day-old pups. Tonic-clonic seizures were delayed by ethosuximide in 12-, 18-, and 90-day-old rats. Picrotoxin-induced lethality was suppressed only in 18- and 90-day-old rats by the 250-mg/kg dose of ethosuximide. In contrast, ethosuximide pretreatment increased the incidence of clonic seizures in 12-day-old rats. The results suggest that only high doses of ethosuximide can suppress clonic seizures, and this action is not consistent. Tonic-clonic seizures probably have model-specific sensitivity to ethosuximide because in previous studies ethosuximide completely suppressed pentylenetetrazol induced tonic-clonic seizures but had no effect on kainic acid-induced tonic clonic seizures. The suppression of mortality rates is probably due to nonspecific effects of high doses of ethosuximide. PMID- 8469709 TI - Development of rapid tolerance to pentobarbital and cross-tolerance to ethanol on a motor performance test with intoxicated practice. AB - Male Wistar rats given a single moderate dose (1.7 mg/kg, IP) of pentobarbital (PB), followed by six trials on the moving belt apparatus during the next hour, showed tolerance to the motor-impairing effects of a second dose of 17 mg/kg given 24 h later. A control group that received saline before the first test showed the usual initial sensitivity when tested with PB 24 h later. Three weeks later, the first group showed cross-tolerance to the effects of ethanol (1.7 g/kg, IP) on the same test, while the second group did not. These findings support the suggestion that rapid tolerance is closely similar to chronic tolerance and that the contribution of intoxicated practice results in a long lasting component that applies to cross-tolerance to ethanol on the same test. PMID- 8469710 TI - Angiotensin II mediates a conditioned taste aversion in water-replete rats. AB - Many compounds that exert an influence on behavioral processes will, under the unique conditions of the conditioned taste aversion (CTA) procedure, cause animals to avoid consuming an otherwise preferred fluid. While angiotensin II (ANG II) is a peptide with a number of behavioral and physiological actions, previous research did not support its role as an agent capable of inducing a CTA. Those studies used fluid deprivation to induce fluid intake and only a single conditioning trial. Fluid deprivation can elevate endogenous ANG II levels that may have interfered with or masked the ability of ANG II injections to exert an effect as a CTA-inducing agent. The present study reassessed the ability of ANG II to induce a CTA using fully hydrated animals and a number of conditioning trials. ANG II was able to induce a significant taste aversion at a dose five times lower than that used in previous studies. PMID- 8469711 TI - Effects of tianeptine on 5-HTP- and dextrofenfluramine-induced hypophagia in the rat. AB - The aim of this work was to analyze whether tianeptine, a 5-hydroxytryptamine (5 HT) reuptake enhancer, opposes the loss in food intake elicited by 5-HT release. Rats were food deprived for 20 h, pretreated either with saline or 7-[3-chloro-6 methyl-5, 5-dioxo-6,11-dihydro- (c,f)-dibenzo-(1,2-thiazepine)-11-yl-amino] heptanoic acid (tianeptine, 10 mg/kg, IP), and injected 1 h afterwards either with saline, with the 5-HT precursor L-5-hydroxytryptophan (5-HTP, 20 or 40 mg/kg, IP), or with the 5-HT reuptake inhibitor/5-HT releaser dextrofenfluramine (d-FEN, 1.5 or 3 mg/kg, IP). Diets were then presented 30 min later, and individual food intakes were measured 1, 2, 3, and 4 h after food presentation. Saline- and tianeptine-pretreated saline-injected rats ate the most, and to a similar extent, during the first hour of food presentation; however, in these animals tianeptine pretreatment tended to diminish rates of eating throughout the last 3 h of analysis. Administration of 5-HTP or d-FEN triggered immediate dose dependent decreases in food intake that were not affected by tianeptine pretreatment. In addition, tianeptine pretreatment did not alter either brain d FEN or d-norfenfluramine levels, thereby suggesting that the lack of effect of tianeptine against d-FEN-elicited hypophagia could not be accounted for by changes in d-FEN metabolism. This study opens the possibility that tianeptine counteracts the effects of 5-HT release in some paradigms but not in others. PMID- 8469712 TI - Electromyographic analysis of exercises proposed for differential activation of medial and lateral quadriceps femoris muscle components. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether active exercises combining hip adduction with knee extension activate medial components of the quadriceps femoris muscle (QF) more than does knee extension alone. SUBJECTS: Twelve healthy adults (6 men, 6 women), aged 20 to 36 years (mean = 24.8, SD = 5.8), participated in the study. METHODS: The subjects performed quadriceps femoris setting (QS), straight leg raising (SLR), straight leg raising with the hip laterally rotated (SLR/LR), and straight leg raising combined with isometric hip adduction (SLR/ADD). Electromyographic (EMG) activity was recorded from the oblique (VMO) and longitudinal (VML) portions of the vastus medialis, vastus lateralis (VL), and rectus femoris muscles. RESULTS: Comparison of normalized mean EMG magnitudes revealed that the single-joint QF components (VMO, VML, and VL) demonstrated significantly greater activity during QS than during any of the three SLR variations and that SLR/LR and SLR/ADD did not elicit greater relative activity of medial QF components than did QS or SLR. CONCLUSION AND DISCUSSION: These findings do not support the notion that concurrent use of the hip adductors during knee extensor exercises results in preferential strengthening of the VMO. PMID- 8469713 TI - Age differences in movement patterns used to rise from a bed in subjects in the third through fifth decades of age. AB - BACKGROUND AND PURPOSE: The purposes of this study were to describe the movement patterns of middle-aged adults when rising from a bed and to determine whether there are age-related differences in movement patterns across the third through fifth decades of age. SUBJECTS: Ninety-three adults (30 men, 63 women), ranging in age from 30 to 59 years, participated in the study. METHODS: The subjects were videotaped during 10 trials of rising from a bed. Subjects comprised three age groups, as defined by the decades of the thirties, forties, and fifties. Movement patterns for four body regions were used to classify the videotaped performances. The incidence of each movement pattern was determined for each decade and graphed. RESULTS: Subjects in their thirties differed from older subjects in movement patterns used to rise from a bed. Movement pattern incidence varied across age groups for each body region. The movement patterns of one body region predominated in reverse order of a previously proposed developmental sequence. CONCLUSION AND DISCUSSION: Results indicate physical therapists should consider the patient's age when selecting movement patterns to teach. PMID- 8469714 TI - Effect of total contact cast immobilization on subtalar and talocrural joint motion in patients with diabetes mellitus. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of total contact casting (TCC) on dorsiflexion at the talocrural joint (TCJ) and motion (inversion/eversion) at the subtalar joint (STJ). SUBJECTS: Thirty-seven patients (29 men, 8 women), ranging in age from 32 to 79 years (mean = 54, SD = 11), with diabetes mellitus and a unilateral plantar ulceration participated in the study. METHODS: The subjects were measured with a goniometer for dorsiflexion and STJ range of motion (ROM). The ROMs for each subject's casted and noncasted legs were compared before and after treatment with TCC for neuropathic plantar ulcers by use of a 2 x 2 repeated-measures analysis of variance design. RESULTS: Mean time of immobilization in TCC (healing time) was 42 days (SD = 43, range = 8 119). The results indicated (1) ROM was unchanged at the STJ, but dorsiflexion decreased slightly (1 degree) on both the casted and noncasted sides following the last cast removal, and (2) ROM was less on the ulcerated side prior to casting compared with the nonulcerated side. CONCLUSION AND DISCUSSION: We believe the beneficial effects (healing of wounds) outweigh the minimal detrimental effects (decreased dorsiflexion) of treatment with TCC. PMID- 8469715 TI - Converting Chattecx Balance System vertical reaction force measurements to center of pressure excursion measurements. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine the precision with which the postural stability data generated by the Chattecx Balance System could be converted to center of pressure displacement measurements. SUBJECTS: Two men and one woman were selected to represent a broad range of body sizes (age = 23-33 years, height = 154-175 cm, weight = 45-80 kg). METHODS: The Balance System load cells were placed on a force plate, and data were collected simultaneously from the Balance System and the force plate while the subjects performed standardized postural tasks. Linear regression analysis was used to characterize the relationship between the estimated center of pressure from the Balance System and the calculated center of pressure from the force plate. RESULTS: Significant linear relationships between the center of pressure estimated from the Balance System and the center of pressure calculated from the force plate were determined (all R2 values = > .90). CONCLUSION AND DISCUSSION: System data can be converted, and the methods recommended for use with the Balance System are described. PMID- 8469717 TI - DPT controversy. PMID- 8469716 TI - Cross-validation of bioelectrical impedance analysis of body composition in children and adolescents. AB - BACKGROUND AND PURPOSE: The reliability and validity of measurements obtained with two bioelectrical impedance analyzers (BIAs), an RJL Systems model BIA-103 and a Berkeley Medical Research BMR-2000, were investigated using the manufacturers' prediction equations for the assessment of fat-free mass (FFM) (in kilograms) in children and adolescents. SUBJECTS: Forty-seven healthy children and adolescents (23 male, 24 female), ranging in age from 8 to 20 years (mean = 12.1, SD = 2.3), participated. METHODS: In the context of a repeated-measures design, the data were analyzed according to gender and maturation (Tanner staging). Hydrostatic weighing (HYDRO) and Lohman's Siri age-adjusted body density prediction equation served as the criteria for validating the BIA obtained measurements. RESULTS: High intraclass correlation coefficients (ICC > or = .987) demonstrated good test-retest (between-week) measurement reliability for HYDRO and both BIA methods. Between-method (HYDRO versus BIA) correlation coefficients were high for both boys and girls (r > or = .97). The standard errors of estimate (SEEs) for FFM were slightly larger for boys than for girls and were consistently smaller for the RJL system than for the BMR system (RJL SEE = 1.8 kg for boys, 1.3 kg for girls; BMR SEE = 2.4 kg for boys, 1.9 kg for girls). The coefficients of determination were high for both BIA methods (r2 > or = .929). Total prediction errors (TEs) for FFM showed similar between-method trends (RJL TE = 2.1 kg for boys, 1.5 kg for girls; BMR TE = 4.4 kg for boys, 1.9 kg for girls). DISCUSSION AND CONCLUSION: This study demonstrated that the RJL BIA with the manufacturer's prediction equations can be used to reliably and accurately assess FFM in 8- to 20-year-old children and adolescents. The prediction of FFM by the BMR system was acceptable for girls, but significant overprediction of FFM for boys was noted. PMID- 8469718 TI - Partition of plasmid R1: a computer simulation. AB - A computer-simulated population of individual Escherichia coli cells harboring plasmid R1 parA+/parB- has been used to analyze three possible modes of plasmid segregation: equi-partition, in which plasmids are partitioned equally to daughter cells at cell division; single-site inheritance, in which the products of the most recent replication event are partitioned equally and the remaining plasmids are distributed randomly; and pair-site partition, in which a single, randomly chosen plasmid is actively partitioned to each daughter cell at division and the rest are distributed randomly. Comparison between predicted and experimental plasmid loss-frequency enabled us to rule out the first of these models as a likely mode of action in R1 but was inconclusive regarding the other two. The parA region would therefore seem to partition actively only one pair of plasmids to each daughter cell, the precise selection rule involved remaining unresolved. This question is not easily decided with current technology, as we show, but our simulation results also predict that the isolation of rep(Ts) mutants will provide an experimental system in which a clear distinction is possible between two plasmids that are the products of the most recent replication event and two that are chosen strictly at random. PMID- 8469719 TI - Characterization, sequence, and replication of a small cryptic plasmid from Selenomonas ruminantium subspecies lactilytica. AB - A 2.5-kb cryptic plasmid, pJDB21, from the gram-negative ruminal anaerobe, Selenomonas ruminantium subspecies lactilytica, was mapped and sequenced. Five open reading frames (ORFs) were predicted and expression of two ORFs was demonstrated. Analysis of the predicted amino acid sequence of the ORF 1 protein indicated approximately 30% homology with the replication protein (rep) common to many gram-positive plasmids, and a highly conserved sequence representing the origin of replication in these plasmids was located upstream of ORF 1. This finding was consistent with a rolling circle form of replication for pJDB21. Transformation of Escherichia coli K-12 UB1636pol Ats with pJDB21 showed that the plasmid replicated independently of DNA polymerase I and produced a single stranded DNA intermediate. Deletion analyses localized the E. coli replication function to a 1.4-kb sequence that was mapped to the predicted rep gene. PMID- 8469720 TI - Conjugative transfer and in vitro/in vivo stability of the broad-host-range IncP R751 plasmid in Brucella spp. AB - Escherichia coli strain K12 BM14, carrying plasmid R751 (51.4 kb; Tpr, Tra+, IncP), was used as donor in matings with reference strains of the six Brucella nomenspecies, not known so far to harbor naturally occurring plasmids. R751 was easily transferred to and between Brucella spp., at frequencies ranging between 10(-1) and 10(-4). All Brucella transconjugants stably maintained plasmid R751 both in vitro and in vivo in our experimental conditions. No genetic modification of the plasmid during and after the conjugal transfer process could be deduced from the comparative restriction analysis (BamHI, HindIII, and EcoRI) in each Brucella transconjugant and in the E. coli donor. PMID- 8469721 TI - The Ti plasmid from the wide host range Agrobacterium vitis strain Tm4: map and homology with other Ti plasmids. AB - The octopine/cucumopine (o/c) strains of Agrobacterium vitis are divided into limited (LHR) and wide host range (WHR) strains. We present here the first map of a Ti plasmid from a WHR o/c strain, Tm4. pTiTm4 (252 kb) has homology with the octopine Ti plasmid pTiAch5, the nopaline plasmid pTiC58, and the Ri plasmid pRiHRI. Approximately 155 kb of pTiTm4 is homologous with the LHR o/c Ti plasmids pTiAB3 and pTiAg57, the remaining part is pTiTm4-specific. Our data suggest that the evolution of the o/c Ti plasmids was accompanied by large-scale changes in plasmid structure. The origin of replication of pTiTm4 was localized by a functional assay. PMID- 8469722 TI - New suicide vector for gene replacement in yersiniae and other gram-negative bacteria. AB - A suicide vector named pUK4134 was constructed to enlarge the repertoire of vectors available for allelic exchange of mutated sequences in gram-negative bacteria. This plasmid combines the properties of two previously described plasmid vectors, pJM703.1 and pRTP1. pUK4134 is a suicide vector, carrying the origin of replication of the plasmid R6K and thus requiring the product of the pir gene for its stable maintenance. The rpsL gene encoding Escherichia coli ribosomal protein S12 confers streptomycin sensitivity on streptomycin-resistant strains and provides a positive selection for bacteria that have lost the plasmid following allelic exchange. The bla gene provides for selection by Apr. Other features are a unique EcoRV cloning site, oriT of plasmid RK2, and the bacteriophage lambda cos sequence. This vector was successfully used several times to carry out allelic exchange in Yersinia pestis. PMID- 8469723 TI - Occurrence of extrachromosomal deoxyribonucleic acids in spiroplasmas associated with plants, insects, and ticks. AB - Several spiroplasmas (helical, motile mollicutes) were previously shown to contain extrachromosomal DNA (E-DNA) elements in the form of viruses (double stranded viruses or the replicative form of single-stranded viruses) or plasmids. These elements are now being investigated as potential vectors for use in spiroplasma transformation systems. Described herein is the first extensive survey of spiroplasma E-DNA in 23 spiroplasma groups (30 strains), a study facilitated by improvements in protocols for E-DNA extraction. E-DNA elements were found in spiroplasmas associated with leafhoppers/plants (spiroplasma subgroups I-1, I-3, and I-8), other insects (subgroups I-2, I-5, I-6, and I-7 and groups IV and XXII), and ticks (subgroup I-4 and groups V and VI). Elements, maintained by passage with their host spiroplasmas, were often lost after extended passage. Whether the current distribution of E-DNA elements is indicative of historical or proximate factors is not known. Many elements (about 75%) from group I spiroplasmas hybridized with Spiroplasma citri viruses SpV1 or SpV3. Of the elements associated with other spiroplasma groups, none hybridized with either virus. These include Spiroplasma apis strains B31 (18 kb) and L89 (18 and 20 kb), S. mirum strains SMCA (20 kb) and Anderson (16 and 20 kb), group VI strain Y32 (7, 9, 10, and 16 kb), and group XXII strain CT-1 (8 kb). Several of these elements will be characterized and examined for their suitability as spiroplasma cloning vectors. PMID- 8469724 TI - Control of mini-R1 plasmid replication: a computer simulation. AB - A molecular model for the control of plasmid R1 replication has been proposed by Nordstrom, Molin and Light (Plasmid 12, 71-90, 1984), involving three genes: repA, copA, copB. RepA codes for a polypeptide whose synthesis is required for initiation; replication is controlled by regulating this synthesis. CopA encodes a small, unstable, untranslated RNA molecule that inhibits translation of the repA message whereas copB produces a protein that inhibits transcription from the repA promoter. We have recast this model into precise mathematical terms and tested it by computer simulation of a synchronous culture in steady-state balanced growth, composed of individual Escherichia coli cells harboring the small, unstable derivative, mini-R1. All single-cell steady-state distributions obtained are independent of initial conditions, and the average values of various plasmid-related variables are similar to those measured experimentally. The relationship between the number of replication events per cell and the copy number at birth, as predicted by the model, mitigates against a sensitive correction mechanism for cells born with other than average copy number and is much closer quantitatively to a nonresponse system, although there is a weak dependence on copy number. The effect of the convergent transcription initiated at the repA and copB promoters on the expression of the copA gene is found to contribute little to the stability of mini-R1 replicons under steady-state growth conditions or to their potential for survival following infection. In fact, the role of the entire CopB control loop is shown to be quite minor, both in steady state and after infection. It is pointed out that genetic manipulations are far more easily performed in silico than in vivo but that results of the kind presented here are very often possible only when simulating individual cells. PMID- 8469725 TI - Harvard Community Health Plan's Mental Health Redesign Project: a managerial and clinical partnership. AB - Harvard Community Health Plan, founded in 1969 as a staff model HMO, is currently a staff and group model HMO with 521,000 members, 19 health centers and 12 independently owned group practices with 26 locations. In 1987, the Plan initiated a review of its mental health benefit and program because its costs were rising, member and clinician dissatisfaction was increasing and many believed the problem was the nature and scope of the benefit. After two years of study, surveys, interviews, cost and utilization analysis, the Plan identified its professional staff as its key asset but recognized many problem areas, including problems with access, variation from site to site, inconsistent service delivery, lack of consistent utilization management and the need for greater diversity along the spectrum of care available to members. From 1989 to 1990, more than 200 clinicians and support staff were engaged in the process of developing a variety of components to the "mental health redesign program." Three simultaneous efforts included developing a method of categorizing patients, restructuring the delivery system and redesigning the benefit. A Mental Health Patient Assessment Tool was created which assists clinicians in performing comprehensive evaluations, administers the benefit, measures progress and supports outcomes research. Delivery system changes included the implementation of self-referral, access standards, intake triage functions by non-clinical staff, program development and an outpatient utilization management function. PMID- 8469726 TI - Staff model HMO's and managed mental health care: one plan's experience. AB - HMO staff model mental health programs have particular expertise in providing these services in an integrated fashion within the context of a total medical care system. "Carve-out" approaches to managed mental health care risk losing the added value found in primary care based integrated mental health services. Employers as purchasers of care are seeking demonstrated value in services, and the rise of specialty mental health managed care firms is bringing the efficiencies of managed mental health care familiar to HMO's to a broader audience. Faced with employer concerns, and this new competitive environment, many HMO's are examining their mental health services to determine how these services may respond to the needs being expressed by employers today for new program options. The Community Health Plan's (CHP) experience is presented to illustrates one approach HMO's are taking in today's competitive health care environment. PMID- 8469727 TI - View from the bridge: reflections of a recovering staff model HMO psychiatrist. AB - The phenomenon of managed care is misperceived by its critics as a movement. Atheoretical in nature, and driven by spiralling health care costs, it represents the introduction of an executive function into the free-for-all (a supremely ironic term) of American medicine. Part one of this article traces the origin and development of the mental health carve-out, relating it to its antecedents, and describing its 3 overlapping phases: utilization review, discounted fees, and network development and management. Part two describes the key concept of the continuum of care and the role of the case manager in monitoring a care episode. The article concludes by anticipating seven future trends and calling for mental health leadership to recognize and ally with the need to manage resources in a more rational and efficient manner. PMID- 8469728 TI - Overview of the HMO movement. AB - This article provides a short historical review of the HMO movement to set the stage for current HMO developments. It notes the underlying causes of the proliferation of HMO managed care models. It defines what should be the rudiments of a quality HMO program and how the changing societal environment will bring new pressures to bear on HMO programs of the future. As related to the future, the author outlines a direction for national health care reforms. The article concludes that the health care emphasis of the 90s should be in returning some of the responsibility of health care to individual Americans through self-care programs that focus on behavioral change, in turn, leading to healthier Americans, the keys to containing out of control health care costs. PMID- 8469729 TI - [The possibility of using the population characteristics of myelokaryocytes for the early diagnosis of radiation lesions]. AB - The method of flow cytofluorimetry was used to study some population characteristics of bone marrow cells of control and irradiated rats. The simultaneous recording of cellularity and distribution of myelokaryocytes among the cell cycle phases was shown to give reliable results for determining the extent to which the organism was exposed at early times following irradiation. PMID- 8469731 TI - [The occurrence of cataract in rats as one of the factors worsening the quality of their lives in the late periods after whole-body and partial irradiation]. AB - A study was made of the formation of cataract in rats at remote times after whole body and partial X irradiation. The whole-body radiation loses were 5 and 10 Gy (two fractions of 5 Gy at a 30-day interval). Partial exposure of the head and neck, as well as irradiation of chest were performed with doses of 5, 10 (two fractions at a 30-day interval) and 15 Gy (three 5 Gy fractions at a 30-day interval). It has been shown that cataract develops not only due to the direct effect of radiation on the eye, but also to indirect effect on the experimental animal body (with irradiation of the abdomen and diabetes development). PMID- 8469730 TI - [The effect of low doses of ionizing radiation on intracellular pH, ATP content and synthetic activity in cultured Chinese hamster fibroblasts]. AB - X irradiation of Chinese fibroblasts with doses of 0.05-0.15 Gy was shown to cause intracellular pH (pHi) changes: its diminishing during the first 40-60 min by 0.16-0.18 pH units, then the return to the control level 120 min after irradiation and, finally, the increase by 0.18-0.20 pH units. Simultaneously, the synthesizing activity of the cells changed in the same way. The ATP level changed in the opposite way: increased when pH fell and decreased when pH grew. It was shown that pHi changes were connected with the changes in Na+/H(+)-exchange system, and they seemed to be primary in the chain of the alterations observed. PMID- 8469732 TI - [The connection between the content of metallothioneins in the bone marrow and liver and the survivability of irradiated mice after cadmium chloride administration]. AB - The survival rate of mice gamma-irradiated at different times after administration of Cd2+ (0.75 mg/kg) was shown to be tightly connected with the amount of metallothioneins induced by this heavy metal in the bone marrow (r = 0.96). The connection between the amount of metallothioneins in the liver and the survival rate was less pronounced. PMID- 8469733 TI - [Synergism and interference in the combined biological action of ionizing and SHF radiation]. AB - In experiments with 933 (CBA x C57Bl)F1 mice it has been found that with any variant of alternation and sequence of single ionizing and SHF irradiation with lethal doses, the radiation affection caused by gamma quanta is aggravated. Preirradiation with gamma or SHF radiation ameliorates the severity of the affection caused by the subsequent SHF radiation. Parenteral injection of colloidal sulfur 60 min before SHF radiation causes a 2-5-fold increase in the survival rate of exposed and protected mice as compared to unprotected animals. PMID- 8469734 TI - [The radioprotective effect of GABA-tropic substances, gamma-hydroxybutyrate and piracetam]. AB - From experiments in mice, it is shown that with a radiation dose of 8 Gy (LD96) the radioprotective effect was exerted by gamma-aminobutyric acid (GABA), substances that increase its concentration in tissues (progabide and valproate), and synthetic agonists of both receptor types, particularly baclofen, a GABA receptor agonist. The radioprotective effect is also exerted by gamma hydroxybutyrate, not piracetam. PMID- 8469735 TI - [An increase in the radioprotective effect of O-methyltyramine and mezaton by monoamine oxidase inhibitors]. AB - Specific 2-propynylamine inhibitors of monoamine oxidase (MAO) pargyline and especially chlorgyline, a selective inhibitor of MAO A (but not deprenyl, a selective inhibitor of MAO B) increase the radioprotective effect of small doses of O-methyltyramine and phenylephrine and do not change the efficacy of large doses. This is consistent with the receptor theory of the mechanism of protective action of amines. PMID- 8469737 TI - [The modification of the radiation damage to the chromosomes in the somatic cells of radiosensitive Drosophila mutants. The effect of fractionating the gamma-ray dose]. AB - A study was made of the effect of gamma-ray dose fractionation registered by chromosome aberration induction in somatic cells of the mutant rad(2)201G1, the mutant mus(2)201G1, and the wild type strain of drosophila. The dose fractionation upon irradiation of the mutant mus(2)201G1 and control strain larvae was shown to decrease the frequency of cytogenetic damages to cells. In contrast, when the radiosensitive mutant rad(2)201G1 was exposed, the effect of dose fractionation was insignificant. PMID- 8469736 TI - [The radioprotective action of an extract of regenerating spleen]. AB - An extract from regenerating calf spleen increases the survival rate of mice when injected after irradiation. The studies of the blood and immune systems characteristics at the subcellular, cellular and tissue levels have been shown that the preparation containing a complex of hemoregulating compounds modifies the processes responsible for radiation damage and repair. PMID- 8469738 TI - [The radioecological problems of Eurasia and the sources of radioactive environmental contamination in the former USSR]. AB - There is three major sites of radioactive environmental contamination in the former USSR: the Chelyabinsk region in the Urals, Chernobyl NPP in Ukraine and Novaya Zemlya in the Arctic Ocean. The first mentioned is the most important with regard to local (potential) contamination, the last one dominates the global contamination. A number of sites and sources are less well known with regard to environmental contamination. This is thus the case for the plutonium production factories at Tomsk and Dodonovo. More information on nuclear reactors in lost or dumped submarines is also needed. From a global point of view reliable assessment of the radioactive run-off from land and deposits of nuclear waste in the Arctic Ocean are in particular pertinent. PMID- 8469739 TI - [The modification of the radiation damage to the chromosomes in the somatic cells of radiosensitive Drosophila mutants. The radioprotective action of cysteamine]. AB - The radioprotective effect of cysteamine has been studied in larva nerve ganglia of the radiosensitive mutant rad(20)201G1, mutagen-sensitive mutant mus(2)201G1 and the control strain of drosophila. Cysteamine was shown to produce a radioprotective effect in somatic cells of mus(2)201G1 and the control strain of drosophila which was manifested by the decreased incidence of cells with chromosome aberrations and diminished yield of deletions and exchanges. No significant radioprotective effect of cysteamine was observed in somatic cells of rad(2)201G1 mutant. PMID- 8469741 TI - [The ultrastructural organization of pine needles after radiation exposure]. AB - Pine assimilative tissue was studied in the region of Chernobyl Power Plant accident the 1986-1988. With radiation doses of 8-11 Gy pine needle was viable inspite of the significant structural changes in cell organelles. With doses of 20-25 Gy the inner structure of mesophyll cells was impaired. High radiosensitivity was displayed by mitochondria and chloroplasts where irreversible destruction of membrane systems occurred. PMID- 8469740 TI - [The modification of the effect of microwave radiation on the biochemical processes in anaphylactic shock by using exposure to a weak and perturbed geomagnetic field]. AB - Repeated exposure of guinea pigs to microwave radiation (1 mW/cm2) caused in some animals inhibition of anaphylactic response accompanied by increasing the content of histamine, epinephrine and norepinephrine in the blood. This increase was more pronounced in irradiated guinea pigs died from anaphylactic shock than in nonirradiated animals. The long-term stay in the perturbed and weak geometric field reduced the effect induced by microwave radiation. PMID- 8469742 TI - [The radioecological lessons of Chernobyl]. AB - This paper presents the results of radioecological studies undertaken within the area exposed to ionizing radiation after Chernobyl disaster. Conclusions are made concerning the major regularities in radionuclide migration within various natural media and action of ionizing radiation on natural and artificial ecosystems. The efficiency of basic protective ecological measures in eliminating the accident consequences has been determined. The contribution of radioecological studies to the elimination of Chernobyl disaster sequences assessed. PMID- 8469743 TI - [The effect of ionizing radiation and calcium on plasma membrane structure]. AB - Plasma membrane thymocytes were irradiated with doses of 10-10(4) Gy in the presence of 125 and 1125 mu mol of Ca2+ per 1 mg of membrane proteins. Fluorescence of 1-anilinonaphthalene-8-sulphonate and the degree of pyren eximerization were determined. The data obtained indicate that calcium can exert a stabilizing effect on the plasma membrane structure affected by radiation. PMID- 8469744 TI - [Structural changes in the plasma membranes during thymocyte irradiation]. AB - Thymocytes were irradiated with doses of 4 to 10(3) Gy. The binding of 1-anilino naphthalene-8-sulphonate and Ca2+ to plasma membranes; viscosity and lipid peroxidation; Stern-Folmer constant; and the number of SH-groups of membrane proteins were determined. The structural changes in plasma membranes after irradiation of thymocytes were found to be cooperative. PMID- 8469745 TI - [Postradiation changes in Ca2+ binding with thymocyte plasma membranes]. AB - Was determined quantity places and constant binding of calcium with plasma membranes thymocytes at rats, that was irradiation at doses 7 Gr. Was establish that to 22 days after irradiation the binding Ca2+ with membranes was return to control. PMID- 8469746 TI - [Changes in the lipid component of thymocyte plasma membranes in exposure to ionizing radiation]. AB - A thymocyte plasma membrane suspension was irradiated with a dose of 5 +/- 10(4) Gy. An increase in the rate of lipid peroxidation and a change in the phospholipid composition of membranes were revealed. The alteration of the plasma membrane structure was characterized by a change in the membrane charge and a decrease in the lipid viscosity. PMID- 8469747 TI - [The effect of alimentary vitamin E on the seasonal fluctuations in the level of fluorescent lipopigments in the tissues of irradiated rats]. AB - In seasonal experiments (spring and autumn) with Wistar female rats, a study was made of the level of lipopigments (LP) and alpha-tocopherol (TPh) fluorescence in the liver and brain. Seasonal peculiarities of the parameters under study and their dependence on Vitamin E ingestion have been revealed. After irradiation of animals, an intimate morphofunctional relationship between LP and TP and its sensitivity to alimentary factors have been found. One hour following irradiation, part of LP is disintegrated thus releasing the TPh reserve. This may be the part of the complex of adaptation changes on the postirradiation metabolic effects. PMID- 8469748 TI - [The physicochemical status of the plasma membranes of rat fatty tissue and liver in the late periods after gamma irradiation at a dose of 1 Gy. Changes in the lipid composition]. AB - A study was made of lipid composition of plasma membranes of adipose tissue and liver of rats at remote times (from 15 to 380 days) after single 1-Gy gamma irradiation. The changes in membrane lipids were most pronounced during the first 50 days after irradiation: the cholesterol level increased (the phospholipid content in the adipose tissue decreased) and the relative content of linoleic (18:2), arachidonic (20:4) and other unsaturated fatty acids decreased. At later times following irradiation, the molar cholesterol/phospholipid ratio in membranes of experimental animals did not vary from the control and relative content of unsaturated fatty acids somewhat increased as compared to that of intact animals of the same age. PMID- 8469749 TI - [The physicochemical status of the plasma membranes of rat fatty tissue and liver in the late periods after gamma irradiation at a dose of 1 Gy. Structural changes in the membranes]. AB - The structural status of plasma membranes of adipose tissue and liver of rats was investigated at remote times (from 15 to 380 days) after single 1-Gy gamma irradiation. The structural status was estimated by pyrene excimerisation parameters and also by both induction resonance energy transfer method and membrane tryptophan fluorescence spectral characteristics. On days 50-100 following irradiation the microviscosity of a lipid phase of membranes increased and the mode of lipid/protein interactions changed, whereas at later times the indices under study did not vary from the controls. Comparison of the data obtained with the former results on lipid content changes indicates that the physicochemical status of plasma membranes in rat adipose tissue and liver is modified at remote times following 1-Gy gamma irradiation. PMID- 8469750 TI - [Can postradiation cell fusion be a factor in the protection of a cell population?]. AB - From the analysis of the literature it is inferred that there is one more type of nonspecific protection which is based on the polyploidy process and functions at the cell population and tissue levels. With high radiation loads, this process maintains the functioning rate of the given tissue and the survival rate of the given cell type. A hypothesis is proposed that cell fusion and formation of somatic hybrids, that provide clone survival, are particularly effective in tumor tissues. This mechanism is activated at high radiation doses: fusion of injured cells and formation of polykaryons and then hybrids can give rise to cells capable of reproduction. The cellularity is restored. PMID- 8469752 TI - [The late effects in treated dogs with a history of acute radiation sickness. The hemodynamic status at different times after irradiation]. AB - Dogs were exposed to X radiation at a dose of 15 Gy; part of them received a complex treatment. The morphological studies of internal organs of control dogs were made before death (on days 4 to 15 after irradiation). The treated dogs were killed 0.5-2 years following irradiation. Hemodynamics normalization was noted in 1.5-2 years in the liver, brain cortex, adrenals, insular tissue of the pancreas, and lymph nodes. PMID- 8469751 TI - [The effect of x-ray irradiation on the production of interleukin-6 and tumor necrosis factor-alpha by mononuclear cells of the peripheral blood]. AB - The influence of X-radiation on production of interleukin-6 (IL-6) and alpha tumor necrosis factor (TNF) has been investigated. Irradiation with doses of 45, 90 and 900 cGy was shown to increase considerably TNF and IL-6 production both in intact mononuclear cultures of human peripheral blood and in cultures stimulated by phytohemagglutinin. In addition to an absolute increase in the production, the stimulatory effect was manifested by earlier accumulation of IL-6 and TNF activities in supernatant fractions of the cultures under study. PMID- 8469753 TI - [Transbrachial arterial catheter angiography. Technique, indications, complications]. AB - In a large group of patients, most of whom were attending a department of vascular surgery, who underwent arterial digital subtraction angiography (DSA), a transfemoral approach was not possible in 9%. Therefore in 142 cases transbrachial arterial angiography was electively performed with 4-F or 5-F catheters. This method proved to be a safe and reliable alternative, though the examination technique was more demanding and the complication rate somewhat higher. It offers clear advantages over a transaxillary or translumbar approach. Special attention is paid to the role of transbrachial arterial DSA in evaluating the descending aorta and the peripheral outflow in the legs and to its usefulness in certain angioplasty manoeuvres. PMID- 8469754 TI - [Widening of the retrorectal space. Pelvic lipomatosis]. PMID- 8469755 TI - [Magnetic resonance in Switzerland today]. PMID- 8469756 TI - [Magnetic resonance imaging. Sequences, options, indications]. AB - In the last few years several new MR sequences have been developed an even more imaging options have become available. In this paper, the properties of all the important MR sequences and their possible variations are discussed and their use in different clinical settings is addressed. PMID- 8469757 TI - [Magnetic resonance imaging in neuroradiology. Indications and applications]. AB - On the basis of own experience with 250 MR-Angiographies and with reference to the literature the authors report on the role MR-Angiography is assuming in neuroradiological diagnostic procedures. As a noninvasive method MR-Angiography contributes to the evaluation of vessel stenosis and occlusion, venous sinus thrombosis and neurovascular compression syndromes. It supports the work-up of space-occupying lesions, as well as arteriovenous malformations and aneurysms. In addition to the diagnosis, follow-up examinations serve as a noninvasive means of therapy control particularly after interventional endovascular procedures. Knowledge of the diagnostic capabilities and limitations, the choice of the correct examination technique and modification of technical variables contribute to establish MR-Angiography as a valuable adjunct to MR imaging. PMID- 8469758 TI - [MR angiography of the abdomen]. AB - The two techniques currently most often used for MR angiography, those based on time-of-flight effects and on phase-contrast, are introduced, and our results with three-dimensional phase contrast angiography of the abdomen are presented. Several basic differences from other imaging procedures render MR angiography clinically useful for screening for renal artery stenosis in critical situations, such as renal failure or intolerance to contrast agents. In the future, the spectrum of applications of MR angiography will broaden and include other indications, such as portal venous hypertension and follow-up studies after surgical portal systemic shunting. PMID- 8469759 TI - [Imaging of the pericardium using magnetic resonance]. AB - Evaluation of the pericardium has been rediscovered with the advent of sectional imaging modalities such as magnetic resonance. Owing to the improved image quality, faster imaging and cine display, MRI has proved to have a useful role in assessment of the pericardium. This article illustrates the authors' wide experience with MRI of normal and abnormal pericardium in numerous patients. The anatomy of the normal pericardium is reviewed, as are the different MR imaging techniques used Advantages of MRI in specific situations are discussed. Congenital anomalies are covered but particular attention is paid to acquired diseases, such as pericardial effusions, with emphasis on the characterization of the different pericardiac fluid collections. Pericardial thickening and constrictive pericarditis, which are easily differentiated from restrictive cardiomyopathy, are also discussed. Finally, primary and metastatic tumors are described. PMID- 8469760 TI - [Evaluation of underexposed conventional x-ray films following digitization]. AB - Inadequate exposure of analogue radiographs is reported in the literature to occur in 5-25% of cases. Therefore, the present study was performed to test whether selective image processing after digitization could reveal diagnostic details on underexposed radiographs. In addition, the minimal exposure values required for diagnostic purposes after adequate image processing were studied. Phantom studies, organ preparations and measurements of physical parameters with decreasing exposure values were performed. The detection of anatomic and pathologic (nondisplaced fracture lines, microcalcification and renal stones) structures were evaluated by 12 readers. Radiographs with exposure values 20-40% lower than "ideal" values can provide adequate diagnostic images after digital processing. The diagnostic information is significantly impaired with values under 50% of the correct exposure values. In conclusion, this method is adequate to save underexposed radiographs for diagnostic purposes and to avoid repeated examinations. PMID- 8469762 TI - Victorian nurses warn of coalition's I.R. policy. PMID- 8469761 TI - Politics and nursing: "Pick your package". PMID- 8469763 TI - Keep Medicare healthy. PMID- 8469764 TI - Career structure review. PMID- 8469765 TI - Australian Nursing Federation health policy. PMID- 8469766 TI - Immunohistochemical demonstration of angiotensin II receptors in rat brain by use of an anti-idiotypic antibody. AB - In the present study we investigated the ability of an anti-idiotypic antibody which recognizes angiotensin II (AII) receptors to demonstrate the presence of such receptors under immunohistochemical conditions. The experiments revealed punctate immunoreactive granules on neurons of the nucleus supraopticus and of the nucleus paraventricularis of the hypothalamus. This localization of AII receptors is consistent with the findings obtained using other experimental approaches to the brain renin-angiotensin system. The conclusion of this study is that the applied anti-idiotypic antibody seems to be a reliable tool for mapping AII receptor distribution. The established experimental approaches to AII receptors are thus now supplemented with the possibility of immunohistochemical investigation. Moreover, the possible microscopic analysis of AII receptors on distinct cells will allow studies at an ultrastructural level. PMID- 8469767 TI - Distribution of angiotensin II receptor subtypes in the rabbit brain. AB - We have determined the distribution of angiotensin II receptor subtypes in rabbit brain using in vitro autoradiography. AT1 receptors were found in very high concentrations in the forebrain circumventricular organs--the subfornical organ, organum vasculosum of the lamina terminalis, and the median eminence as observed in other mammals. However, there was very little labeling in the area postrema. In the paraventricular nucleus, median preoptic nucleus, supraoptic nucleus there were high levels of predominantly AT1 receptors. High densities of AT1 receptors were also found in the nucleus of the solitary tract and the rostral and caudal ventrolateral medulla. All of these regions have putative roles in the regulation of blood pressure and fluid and electrolyte balance. In the rabbit brain there is less AT2 receptor binding than the rat, with most AT2 binding found in the molecular layer of the cerebellum and in the septohypothalamic nucleus. In the subthalamic nucleus, the mediodorsal and ventroposterior nuclei of the thalamus, locus coeruleus and inferior olivary nuclei, areas containing mostly AT2 receptors in the rat, no binding was detected in the rabbit except in the locus coeruleus which contains moderate levels of AT1 receptors. Taken in conjunction with our previous results in the rat and human brains, these results reveal that AT1 receptors predominate in rostral forebrain, hypothalamus and autonomic control centers of the medulla oblongata in all three species. However, the distribution and density of AT2 bearing sites in regions such as the septum, thalamus subthalamic nuclei, locus coeruleus, cerebellum and inferior olivary nuclei show marked species differences. PMID- 8469768 TI - Binding and signal transduction of the cloned vascular angiotensin II (AT1a) receptor cDNA stably expressed in Chinese hamster ovary cells. AB - The vascular angiotensin (A) II receptor cDNA (AT1a) was transfected into Chinese hamster ovary (CHO) cells to generate the stable cell line CHO-AT1a. This cell line was used to investigate the binding and signal transduction properties of the cloned vascular AT1 receptor. Specific binding of sarcosine1( )[125I]tyrosine4-isoleucine8-AII ([125I]SI-AII) to CHO-AT1a membranes reached equilibrium after 1 h at 25 degrees C and was consistently greater than 95% of total binding. Saturation binding analyses demonstrated [125I]SI-AII bound to a saturable population of sites on membranes with an equilibrium dissociation constant (KD) of 0.7 nM and a binding site maximum of 1.2 pmol/mg protein. [125I]SI-AII binding to CHO cells was inhibited by the following compounds with a rank order of potency of SI-AII > AII > losartan > AI >> PD 123,177. AII (1 microM) treatment of CHO-AT1a cells caused an increase in inositol phosphates and intracellular calcium relative to basal levels. These responses were blocked by losartan but not by PD 123,177. AII (1 microM) did not effect adenylate cyclase activity in CHO-AT1a cells, whereas the agonist inhibited adenylate cyclase activity in rat liver cell membranes. These effects were blocked by 10 microM losartan. These results indicate that CHO-AT1a cells express functional AT1a receptors which stimulate phospholipase C activity but not adenylate cyclase activity. CHO-AT1a cells should provide a useful model for studies of AT1a receptor domains which are critical to signaling pathways. PMID- 8469769 TI - Characterization of angiotensin AT1A receptor isoform by its ligand binding signature. AB - The objective of this study was to determine whether the binding signature of the cloned rat AT1A receptor transfected into Chinese hamster ovary cells could be distinguished from that of the endogenous AT1B receptor expressed in rat adrenal cortex. An extensive series of peptide and nonpeptide Ang II analogs was used for the characterization. The binding of [125I]Ang II to the recombinant AT1A receptors was quite sensitive to inhibition by GTP gamma S. Scatchard analysis of the competition of Ang II revealed two populations of binding sites (site 1: KD = 3.05 +/- 0.27 nM and a maximum binding (Bmax) of 134 +/- 26 fmol/mg protein; site 2: KD = 253 +/- 77 nM and Bmax = 1.05 +/- 0.19 pmol/mg protein). The ligand binding signature of the AT1A receptor is defined by the affinity (Ki = nM) and order of potency of the following ligands: saralasin (2.07) > Ang II (3.35) > losartan (14) > Ang III (20) > GR 117289C (28) > EXP6803 (160) > Ang I (281) > PD123177 (> 10,000). This binding signature of the cloned AT1A receptors appears to be similar to that displayed by rat adrenal cortical cells where AT1B is predominantly expressed. These findings suggest that AT1A and AT1B receptors may not be easily distinguishable by the currently available ligand agonists or antagonists. Consequently, AT1A or AT1B may be considered as isoforms rather than subtypes of the AT1 receptors. PMID- 8469770 TI - Signal transduction mediated by angiotensin II receptor subtypes expressed in rat renal mesangial cells. AB - Recent evidence suggests that there are two classes of receptors for angiotensin II (AngII), AT1 which is sensitive to losartan (DuP753) and is G-protein coupled, and AT2 which is sensitive to both PD123319 and CGP42112A, and is non-G-protein coupled. In rat mesangial cells two subtypes of AT1 receptor could be distinguished, AT1A subtype is more sensitive to losartan whereas AT1B subtype is more sensitive to PD123319, but insensitive to CGP42112A. The present studies were designed to ascertain which receptor subtype mediates three AngII-induced physiologic functions in rat mesangial cells namely intracellular Ca2+ mobilization, adenylyl cyclase inhibition and protein synthesis as monitored via [3H]leucine incorporation. The rank order of potency for inhibition of AngII induced [Ca(2+)]i mobilization and adenylyl cyclase regulation was PD123319 > or = losartan > CGP42112A. By contrast, losartan was quite effective at inhibiting protein synthesis (IC50 = 8 nM) while PD123319 was without effect. These findings are consistent with AngII mediated signal transduction through AT1A and AT1B sites for phospholipase C mediated [Ca(2+)]i mobilization and inhibition of adenylyl cyclase. On the other hand, AT1A receptors appear to exclusively mediate AngII-induced protein synthesis. These observations underscore the complexity of AngII mediated signal transduction in glomerular mesangium. PMID- 8469771 TI - Angiotensin II binding sites in the rat fetus: characterization of receptor subtypes and interaction with guanyl nucleotides. AB - Angiotensin II (AII) receptor subtypes were studied in the 18-day gestation fetal rat, using two non-peptide AII antagonists: (2-n-butyl-4-chloro-5-hydroxymethyl-1 (2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl)imidazol (DuP 753; type 1 (AT1) specific), and 1-(4-amino-3-methylphenyl)methyl-5-diphenacetyl -4,5,6,7 tetrahydro-1-H-imidazo[4,5-c]pyridine-6-carboxylic acid (PD 123177; type 2 (AT2) specific). Autoradiography using 125I(-)[Sar1,Ile8]AII showed that 10 microM PD 123177 decreased binding to near-nonspecific levels in skin, skeletal muscle and adrenal medulla, whereas 10 microM DuP 753 blocked binding in the liver and lung. Studies in skin and liver membranes confirmed the autoradiographic data: AT1 receptors were predominant in the liver (95%), and AT2 in the skin (97%). There was no cross-reactivity between receptor subtype and the heterologous antagonist up to a concentration of 10 microM. In both skin and liver, 2 mM dithiothreitol enhanced the binding of AT2 receptors by increasing receptor affinity, but inhibited binding of AT1 by decreasing the receptor number. In the absence of antagonists, guanyl nucleotides, added at equilibrium, caused marked dissociation of 125I-AII binding in liver membranes, but had minimal effect in skin. However, dissociation occurred in the skin when AT2 sites were blocked with 10 microM PD 123177, and in liver, dissociation was not observed when AT1 sites were blocked with DuP 753. Hence, in contrast to classical AII target tissues, which contain predominantly AT1, most of the sites in fetal skin and skeletal muscle are AT2. The demonstration that the effects of guanyl nucleotides are selective for receptor subtype suggests that the AT1 receptor, but not the AT2, is coupled to cell function via guanyl nucleotide binding proteins. The functional importance of the AT2 receptors and their role in fetal physiology is under current investigation. PMID- 8469772 TI - Expression of AT2 receptors in rat fetal subdermal cells. AB - Using an in situ receptor binding assay with emulsion autoradiography, angiotensin II receptors have been localized to the subdermal/subcutaneous region of the E19 rat skin. Radioligand binding studies on membranes of epidermis, dermis, and subdermal tissues confirmed the localization of receptors to these regions and displacement of binding by PD123177 showed the receptor was AT2. Scatchard analysis of whole skin membrane binding studies showed the receptor had a Kd of 0.8 nM, with a Bmax of 2240 fM/mg protein. Fetal mesenchymal cells were placed in culture and angiotensin II binding which was minimal at 48 h increased by 30-50-fold after 96 h in culture with the majority of the receptors being AT2. Increasing concentrations of FBS caused a decrease in angiotensin II binding, while maintaining the same percentage of AT2 binding sites. Increasing the initial cell density at which the cells were plated dramatically increased the angiotensin II radioligand bound, while decreasing the percentage bound to AT2 receptors. These findings demonstrate the presence of both angiotensin II receptor subtypes in cultured skin mesenchymal cells. They also demonstrate that the culture conditions used can either modulate the expression of receptor subtypes or select for cells expressing a receptor phenotype. The lower number of AT2 binding sites in rapidly dividing cell cultures suggests that the AT2 receptor may not have a function in cell replication or growth. PMID- 8469773 TI - [125I]CGP 42112 binding reveals differences between rat brain and adrenal AT2 receptor binding sites. AB - The AT2 angiotensin II receptor selective ligand CGP42112 was radioiodinated and used to study AT2 receptor binding sites in the rat brain (combined olfactory bulb, septum, thalamus and midbrain) and whole adrenal. The [125I]CGP 42112 binding was of high affinity, saturable and specific in both tissues. Competition studies with nonselective and angiotensin II receptor subtype selective ligands, and evaluation of the effects of the sulfhydryl reducing agent beta mercaptoethanol, confirmed that [125I]CGP 42112 bound selectively to the AT2 angiotensin II receptor subtype. [125I]CGP 42112 bound with higher affinity in the brain than in the adrenal. beta-Mercaptoethanol enhanced [125I]CGP 42112 binding in the brain, but did not alter its binding in the adrenal. A similar difference in binding affinity for [125I]sarcosine, isoleucine angiotensin II and enhancement of binding affinity by beta-mercaptoethanol was observed in the rat brain and adrenal. These observations suggest that the AT2 angiotensin II receptor subtypes in the brain and adrenal may differ. PMID- 8469774 TI - Regulated expression of angiotensin II (AT2) binding sites in R3T3 cells. AB - R3T3 cells are a fibroblast cell line found to selectively express the AT2 subtype of angiotensin II binding sites. We have previously shown that in these cells, the AT2 sites do not appear to be coupled to G-proteins, do not modulate any of the common second messenger pathways associated with activation of angiotensin II receptors, and do not internalize bound ligand. Here we report that expression of AT2 sites in these cells are subject to modulation by a variety of conditions. In actively growing cells the expression of AT2 sites is very low, while in confluent, quiescent cells, the expression of AT2 sites is markedly increased. Addition of serum, or growth factors, to quiescent cells causes a rapid decrease in the number of cell-surface AT2 sites. Further, incubation of cells with ligands that bind to AT2 sites causes a marked increase in the number of these sites in a time and dose dependent manner indicating homologous up-regulation of expression. These results indicate that expression of AT2 sites in R3T3 cells is under sensitive and rapid control and further indicate that these cells may be an excellent model for studying the physiological regulation of expression of these sites. PMID- 8469775 TI - Sar1-p-benzoylphenylalanine-angiotensin, a new photoaffinity probe for selective labeling of the type 2 angiotensin receptor. AB - Previous photoaffinity labeling of angiotensin II (Ang) receptors with azidophenylalanine containing Ang analogs produced high yield labeling of a 60 kDa protein on bovine adrenocortical membranes. This preparation is mostly enriched in the type 1 Ang receptor (AT1) and AT1 selective ligands (L158,809) totally prevented labeling, therefore confirming the AT1 nature of the labeled protein. Our attempt to photolabel the type 2 Ang receptor (AT2) of human myometrium with [Sar1,D-Phe(N3)8]Ang was unsuccessful, revealing a high degree of photolabeling selectivity. An Ang analog, [Sar1,Bpa8]Ang (or BpaAng) was prepared containing the photosensitive amino acid p-benzoylphenylalanine (Bpa). This compound was a specific but non-competitive Ang antagonist on rabbit aorta with a pA2 of 8.5. It displayed good binding affinities for bovine adrenocortical membranes (Kd = 6.5 nM), a predominantly AT1 preparation, and for human myometrium membranes (Kd = 0.39 nM), a predominantly AT2 preparation. Photolabeling experiments with iodinated BpaAng showed that AT1 was not covalently labeled whereas AT2 was covalently labeled with high yield. Labeling specificity was verified with the AT2-selective ligand PD123319 and with the AT1 selective antagonist L158,809. Our results indicate that 125I-BpaAng is exclusively labeling AT2 sites. This compound should be a useful tool for further biochemical characterization of the AT2 binding site. PMID- 8469776 TI - Identification and characterization of a novel angiotensin binding site in cultured vascular smooth muscle cells that is specific for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV. AB - This study demonstrates the existence of a previously unrecognized class of angiotensin binding sites on vascular smooth muscle that exhibit high affinity and specificity for the hexapeptide (3-8) fragment of angiotensin II (AngIV). Binding of [125I]AngIV is saturable, reversible and describes a pharmacologic profile that is distinct and separate from the classic AT1 or AT2 angiotensin receptors. Saturation binding studies utilizing cultured vascular smooth muscle cells obtained from bovine aorta (BVSM) revealed that [125I]AngIV bound to a single high affinity site with an associated Hill coefficient of 0.99 +/- 0.003, exhibiting a KD = 1.85 +/- 0.45 nM and a corresponding Bmax = 960 +/- 100 fmol mg 1 protein. Competition binding curves in BVSM demonstrated the following rank order effectiveness: AngIV > AngII(3-7) >> AngIII > Sar1,Ile8 AngII > AngII > AngII(1-7) > AngII(4-8), DuP 753, PD123177. The presence of the non-hydrolyzable GTP analog GTP gamma S, had no effect on [125I]AngIV binding affinity in BVSM. The presence of this novel angiotensin binding site on smooth muscle in high concentration suggests the possibility that this system may play an important, yet unrecognized role in vascular control. PMID- 8469777 TI - Angiotensin II binding sites on micro-organisms contaminating cell cultures. AB - An angiotensin II (Ang II) binding site, distinct from AT1 and AT2, has been found in cell cultures of rat aortic smooth muscle and rat glomerular mesangium. It is characterized by a high affinity for Ang II (Kd 0.75 +/- 0.13 nM) and Ang I (Ki 0.72 +/- 0.12 nM), but a very low affinity for Ang III (Ki 31 +/- 5 microM). Ang(1-7) (Ki 1.01 +/- 0.26 nM) and Ang(1-6) (Ki 4.54 +/- 0.24 nM) are very selective for this site, with affinities more than 150- and 10,000-fold greater, respectively, than for AT1 or AT2. The selective angiotensin receptor subtype ligands losartan and L-158,809 (AT1), PD 123319 and CGP 42112A (AT2) were inactive. Binding to this site was abolished after the cells had been treated with the antibiotic mixture BM-Cyclin, suggesting that the site is located not on the cells, but on a cell culture contaminant. This has been identified as Acholeplasma laidlawii. Caution should therefore be exercised when interpreting Ang II-related data obtained from cells that have not been checked for Mollicute contamination. PMID- 8469778 TI - Immunohistochemical mapping of angiotensin AT1 receptors in the brain. AB - A new approach to study angiotensin receptor distribution in the brain has been taken by developing antibodies to partial sequence of the angiotensin II (AII) type-1 receptor subtype (AT1) and demonstrating the presence of receptors with immunohistochemical staining. The antibody to a portion of the 3rd cytoplasmic loop of the AT1 receptor revealed distinctive punctate immunoreactive staining on cell bodies. The cell bodies were distributed in the forebrain in paraventricular and supraoptic nuclei, the organum vasculosum lamina terminalis, median preoptic area and subfornical organ. In the brainstem, the entire locus coeruleus was stained, together with the adjacent mesencephalic and motor nuclei of the trigeminal nerve. The auditory system including the cochlear nucleus and superior olivary nuclei were stained. In the medulla, all the structures involved in blood pressure control were stained including the nucleus of the solitary tract, the 12th nerve nuclei, the rostroventral lateral area and the nucleus ambiguous. Sites where AT2 receptors are located were not stained or staining was limited to specific area such as the medial accessory nucleus of the inferior olive. Immunocytochemical staining of AT1 receptors provides a new and more precise approach to the cellular localization of AII receptors. PMID- 8469779 TI - Experimental uremia in male rats: effect on the reproductive tract and fertility. AB - Chronic renal failure was induced in 3-month-old male rats by 5/6 nephrectomy. Potency and fertility studies were performed after 3 months of chronic uremia. The mean serum testosterone at the end of the experiments was significantly lower: 0.96 +/- 0.14 ng/mL compared to a control group of sham-operated male rats, 2.86 +/- 0.59 ng/mL, p < .001. All the uremic male rats had normal accessory gland weights at the end of the study. Fertility and, in most animals, sexual behavior and mating were not different from the normal control group. It is concluded that in 5/6-nephrectomized uremic male rats, in spite of low testosterone level, fertility and reproductive system are maintained similar to normal control male rats. PMID- 8469780 TI - Role of glutathione for cisplatin nephrotoxicity in young and adult rats. AB - Investigations were done in 10- and 55-day-old Wistar rats. Glutathione (GSH) level in kidney was decreased by 8 mmol buthionine sulfoximine (BSO)/100 g BW. There was no effect on the renal function and nephrotoxicity of cisplatin (0.6 mg CP/100 g BW) in adult rats. In young rats BSO treatment was followed by nephrotoxic effects. Pt concentration remained unaffected by BSO in young and adult rats. GSH concentration in kidney was increased by 100 mg acetyl-cysteine (accys)/100 g BW. CP nephrotoxicity was lower in young as well as in adult ac-cys treated rats. Pt levels in renal tissue were significantly decreased in rats from both age groups. From our results we conclude that the beneficial effect of high GSH concentration in renal tissue on CP nephrotoxicity is the result of decreased Pt concentration in kidney. PMID- 8469781 TI - Electrophoretic analysis of serum and urinary proteins in rats with aminonucleoside-induced nephrotic syndrome. AB - Albumin; and alpha 1-, alpha 2-, beta-, and gamma-globulins were estimated by cellulose acetate electrophoresis in the serum and urine from rats with nephrotic syndrome (NS), 2, 4, 6, 8, 10, 12, 16, 20, and 30 days after a single injection of puromycin aminonucleoside (PAN). It was found that: (a) total serum protein level decreased on days 4-16, and total urine protein excretion rose on days 6 16; (b) serum albumin level fell on days 4-16, and urine albumin excretion increased on days 6-16; (c) serum alpha 1-globulin level rose on days 8-30, and urine alpha 1-globulin excretion increased on days 8-16; (d) serum alpha 2 globulin level remained essentially unchanged, and urine alpha 2-globulin excretion rose on days 4-10; (e) serum beta-globulin level decreased on days 4 20, and urine beta-globulin excretion increased on days 6-16, (f) serum gamma globulin level diminished on days 6, 8, and 12, and urine gamma-globulin excretion rose on days 6-10. All serum protein fractions were excreted in the urine of nephrotic rats; these findings suggest that proteinuria is nonselective. The differences observed in the serum protein profiles, even when all protein fractions were lost in the urine, suggest an independent regulation of each protein fraction in PAN-nephrotic rats. In addition, the electrophoretic profile of serum proteins in PAN-nephrotic rats is different from previously reported patterns in human nephrosis and in rats with an acute-phase response. PMID- 8469782 TI - Renal function and renal platinum content in uninephrectomized rats following cisplatin administration. AB - The changes in renal function and renal platinum content were assessed in uninephrectomized and sham-operated female Wistar rats on the third day after treatment with 2.5 mg/kg BW or 5 mg/kg BW cisplatin. Treatment of control and nephrectomized rats with 2.5 mg/kg BW cisplatin resulted in indices of renal function which were not significantly different from those of animals which had received no cisplatin, though the renal platinum contents in nephrectomized rats were practically the same as in two-kidney animals given 5 mg/kg BW cisplatin. Treatment with 5 mg/kg cisplatin resulted in much less severe changes in kidney weight and renal function compared to two-kidney animals, in spite of much more substantial (by 49-58%) platinum accumulation. PMID- 8469783 TI - Induction of immediate early and stress genes in rat proximal tubule epithelium following injury: the significance of cytosolic ionized calcium. AB - This study was designed to investigate the influence of intracellular ionized calcium ([Ca2+]i) on the induction of c-fos, c-jun, c-myc, and hsp70 genes after oxidant stress induced by xanthine/xanthine oxidase (X/XOD) treatment or after heat shock using primary cultures of rat proximal tubule epithelium (PTE). X/XOD (500 microM/25 mU/mL) induced all of these genes; ionomycin also resulted in similar kinetics of induction of all genes. The expression of both c-fos following X/XOD treatment and hsp70 following heat shock was markedly decreased through chelation of [Ca2+]i by Quin 2/AM. The c-fos expression following X/XOD treatment was partly reduced by a protein kinase C inhibitor, staurosporine (ST), and markedly inhibited by another protein kinase inhibitor, 2-aminopurine (2AP), while both ST and 2AP markedly reduced hsp70 expression. The ADP-ribosylation transferase inhibitor 3-aminobenzamide had no effect on either c-fos or hsp70 expression. These results suggest that cell injuries leading to increased [Ca2+]i in PTE result in induction of c-fos, c-jun, c-myc, and hsp70; and that the activation of c-fos and hsp70 genes may be regulated by [Ca2+]i and [Ca2+]i dependent protein kinases. PMID- 8469784 TI - Thyroid hormone profiles in experimental acute renal failure. AB - Thyroid hormone profiles were determined in two groups of dogs made uremic, either by i.v. uranyl nitrate 10 mg/kg BW injection or by bilateral ureteral ligation, and in one group of sham-operated animals. Each group consisted of 6 dogs and served as its own control. From blood samples taken in 12-h intervals up to 144 h for uranyl nitrate-injected dogs and 96 h for operated dogs, serum levels of T4, T3, fT4, fT3, rT3, and cortisol were measured by radioimmunoassays. The results obtained in both groups of uremic dogs showed an initial sharp fall of T4, T3, fT4, and fT3 followed by a plateau or retarded decrease. In sham operated dogs the fall of these hormones was slight and of short duration. Reverse T3 had a tendency to increase in all groups examined, but a significant elevation was recorded only after bilateral ureteral ligation. In this group cortisol serum levels were found the highest, being also significantly increased in the other two groups. The temporal coincidence of the most marked alterations in T3, rT3, and cortisol serum concentrations indicates a significant role of stress in thyroid dysfunction. Although serum creatinine rise and weight loss were not parallel with thyroid hormone alterations, the involvement of uremic compounds and malnutrition in this process is also quite clear. Thus, the data presented suggest simultaneous influences of uremic toxins, stress, and malnutrition on the induction of thyroid dysfunction in dogs made uremic by uranyl nitrate injection or bilateral ureteral ligation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469785 TI - Influence of pentoxifylline on renal function in HIV-seropositive patients. AB - Pentoxifylline (PTX) has potential usefulness in HIV-seropositive patients due to its beneficial effects on renal function, its inhibitory effects on tumor necrosis factor alpha, and its vascular effects on microcirculatory disturbances. The present study prospectively evaluated the effects of multiple oral doses of PTX (400 mg three times daily for 12 weeks) on renal function in 11 HIV seropositive patients compared with 14 control patients. Four of these patients had HIV-associated nephropathy, manifested by high urinary microalbumin outputs (72 +/- 56 micrograms/min; mean +/- SD). Ambulatory 24-h urine collections were analyzed for creatinine, electrolytes, and immunological markers at weekly intervals for 12 weeks. Urine flow rates diminished to one-half baseline values by week 12; changes were related to both time and treatment sequences. There were significant decreases in creatinine clearances and electrolyte excretion rates over the study period that were not associated with treatment regimens. No differences were found in fractional electrolyte, uric acid, microalbumin, and neopterin excretion rates either between or within groups. One subject with high microalbumin excretion rates had a significant drop over the 12 weeks (133 to 4 micrograms/min); the other 3 subjects had similar or elevated microalbumin outputs by the end of the study. Although well tolerated, therapeutic doses of PTX did not significantly affect renal function in HIV-seropositive patients. PMID- 8469786 TI - Niceritrol reduces plasma lipoprotein(a) levels in patients undergoing maintenance hemodialysis. AB - Lp(a) is an LDL-like lipoprotein carrying the apoprotein(a) glycoprotein and has recently been recognized to be an independent risk factor for coronary heart disease. We studied plasma Lp(a) levels in 40 patients undergoing maintenance hemodialysis (24 male, 16 female; aged 16-83 years). Fasting plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay. The median value of plasma Lp(a) concentrations in hemodialysis patients was significantly higher than that of the normal volunteers (26.0 +/- 2.7 vs. 10.8 +/- 3.7 mg/dL, p < .05). Lp(a) levels did not correlate with age, duration of hemodialysis, total cholesterol, triglyceride, HDL cholesterol, or LDL cholesterol. The 11 patients whose plasma Lp(a) concentrations exceeded 20 mg/dL received niceritrol, a prodrug of nicotinic acid, at a dosage of 500 mg t.i.d. for 4 weeks. The plasma Lp(a) levels were significantly lower after 4 weeks of treatment (38.3 +/- 4.2 vs. 31.5 +/- 3.2 mg/dL, p < .01). PMID- 8469787 TI - Lithium clearance measurements during recombinant interleukin 2 treatment: tubular dysfunction in man. AB - Renal tubular function was evaluated in nine patients undergoing recombinant interleukin 2 (rIL2) treatment for metastatic colorectal carcinoma. A lithium clearance technique was used and the activities of the lysosomal enzyme N N acetyl-beta-D-glucosaminidase were also measured in the patients' urine, before treatment, during treatment, and then 2 days and 23 days after rIL2 therapy had finished. Significant reductions in clearances of creatinine, sodium, and lithium were observed. The fractional excretions of sodium and lithium were also reduced. Twenty-three days following cessation of rIL2 treatment, there was still a significant reduction in creatinine clearance compared with pretreatment values (p < .01). The clearances of sodium and lithium were also reduced compared with pretreatment values although this did not achieve significance. The fractional reabsorption of sodium and water by the proximal nephron increased during rIL2 treatment, from 0.707 +/- 0.030 (pretreatment) to 0.793 +/- 0.043. This increased reabsorption of sodium and water persisted, rising to 0.849 +/- 0.029, 2 days following cessation of treatment (p < .001, means +/- SEM). Twenty-three days later this had returned toward the pretreatment value, being 0.781 +/- 0.036. The fractional reabsorption of sodium by the distal nephron was also significantly elevated, both during and 2 days after completing rIL2 treatment. Twenty-three days after cessation of rIL2, this value had returned to the pretreatment value. However, in contrast, the fractional reabsorption of water by the distal nephron demonstrated no change during rIL2 treatment, but 2 days posttreatment was significantly reduced and remained low for a further 3 weeks. PMID- 8469788 TI - Preliminary screening of the relationship of serum lipids to survival of chronic dialysis patients. AB - To assess the predictive value of serum lipid measurements in dialysis patients once the initial decrease on early dialysis had occurred, we obtained random serum cholesterol and triglyceride levels in stable, chronic dialysis patients who were then followed up to 9 years. Derived LDL (DLDL) was estimated by the Friedewald formula, calculated for all HDL levels between 30 and 45 mg/dL, and evaluated statistically against a panel of vascular disease markers, including clinical assessment for coronary, peripheral, and cerebrovascular disease; ECG, both standard and ambulatory; two-dimensional echocardiogram; and medications. Survival was calculated from entry (not dialysis onset) for 58 hemodialysis and 33 peritoneal dialysis patients. The 91 patients (49 males, 74 diabetics) were divided by cholesterol level (> or = 175 mg/dL = 53, < 175 = 38), triglyceride (> or = 175 mg/dL = 55, < 175 = 36), and DLDL (> or = 75 = 58, < 75 = 24). High total cholesterol was present in a larger proportion of females than low cholesterol, but groups were not different with respect to all vascular determinants, including survival (mean = 33.4 months vs. 43.2, p = NS). High vs. low triglyceride groups were not different with respect to vascular indicators, except for both incidence of abnormal standard ECG (69% vs. 42%, p < 0.05) and survivals (mean = 42.0 vs. 30.7, p < 0.05; 1 year = 80% vs. 56%, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469789 TI - Cognitive function and quality of life in end-stage renal failure. AB - The Sickness Impact Profile (SIP) and the Wechsler Memory Scale--Revised (WMS-R) were administered to a small sample of end-stage renal failure patients. The memory test successfully discriminated between patients who were rated by their nurses to be well adjusted or poorly adjusted to dialysis treatment. It is concluded that this instrument may be useful in investigating cognitive function in this patient population. PMID- 8469790 TI - Glomerular alterations in experimental oliguric and nonoliguric acute renal failure. AB - Studies were performed in oliguric and nonoliguric forms of uranyl acetate (UA) induced and ischemic acute renal failure (ARF) to examine whether a reduction in GFR is correlated with glomerular morphologic alterations. UA-induced nonoliguric and oliguric ARF were induced in rabbits by i.v. injections of 0.9 and 2 mg/kg, respectively. A 60-min renal artery clamping produced nonoliguric ARF in previously uninephrectomized rats, but oliguric ARF in the clamped kidneys of sham-nephrectomized animals. A decline in the whole-kidney CIn rate was more marked in oliguric ARF kidneys of both models than in nonoliguric ARF kidneys. Also, tubular damage was more pronounced in oliguric kidneys when compared with nonoliguric kidneys. Scanning electron microscopic observations revealed glomerular alterations in oliguric and nonoliguric kidneys in both models, evidenced by a flattening and spreading of podocyte cell bodies associated with loss of epithelial foot processes and a reduction in the density and diameter of endothelial fenestrae. There was no significant difference in these glomerular changes between oliguric and nonoliguric kidneys. The findings suggest that less reduction in the whole-kidney GFR in nonoliguric ARF kidneys is ascribed largely to less pronounced tubular damage rather than to less severe glomerular morphologic alterations. PMID- 8469791 TI - Peritonitis rates in CAPD patients using the UVXD and O-set systems. AB - We report experience with O-set and UVXD systems. Sixty-nine O-set patients (34 male; mean age +/- SD = 45.7 +/- 13.2 years) were compared with 54 UVXD patients (27 male; 56.8 +/- 16.8 years). Total (mean +/- SD) experience were 974 (14.1 +/- 10.8) months on O-set and 1010.9 (18.7 +/- 15.7) months on UVXD. Thirty-two O-set patients avoided peritonitis; 37 had 91 episodes. Seventeen UVXD patients avoided peritonitis; 37 had 137 episodes. Peritonitis occurred each 10.7 months (O-set) versus 7.4 months (UVXD), which was significantly different (p = 0.032, Z test; 95% confidence interval = -0.142 to +0.226). There were 18 relapses in 9 O-set patients, 34 in 12 UVXD. Gram-positive organisms caused 58.2% and 66%; gram negative, 13.2% and 8.8%; and culture negative, 24.2% and 23.4% of peritonitis in O-set and UVXD, respectively. The time to first peritonitis was not different, 7.4 +/- 6.6 months O-set and 7.2 +/- 7.9 months (UVXD). There was no difference in the peritonitis-free period, 13.0 +/- 10.0 months (O-set) and 16.5 +/- 14.3 months (UVXD). There were 1.12 (O-set) and 16.1 (UVXD) cases per patient year, and 10.7 (O-set) and 7.43 (UVXD) patient months per episode. The peritonitis rate odds ratio was 1:1.85 (O-set:UVXD). PMID- 8469792 TI - Circadian blood pressure changes in patients with chronic renal insufficiency: a prospective study. AB - Circadian blood pressure (BP) rhythm was prospectively studied by ambulatory 24-h monitoring in normotensive (n = 27) and hypertensive (n = 41) patients with stable progression of chronic renal insufficiency, and in matched control groups (healthy subjects: n = 28 and patients with essential hypertension: n = 47) without renal disease. The follow-up period lasted 24 months. The renal patients showed a disturbance in the 24-h profile of BP, with significantly blunted nocturnal pressure reduction as compared with the respective control groups (p < 0.01 and p < 0.001, respectively). In addition to the rearrangement of circadian rhythm, the normotensive and hypertensive renal patients displayed a wider distribution of systolic and diastolic BP values and a greater nocturnal variability. Among the normotensive and hypertensive patients with chronic renal insufficiency, a significant correlation was found between the decline in creatinine clearance over the 24-month period and the average nighttime diastolic BP (r = 0.526; p < 0.01 and r = 0.613; p = 0.001, respectively) and nocturnal diastolic fall (r = 0.612; p < 0.001 and r = 0.496; p < 0.01, respectively). These data offer support for the view that renal normotensive patients are exposed to a relative hypertension at nighttime and that renal hypertensive subjects can be underestimated in their hypertensive status if the measurement of BP is confined to daytime. In both groups, nocturnal BP overload can accelerate the progression rate of renal insufficiency. PMID- 8469793 TI - Oxygen saturation during hemodialysis. AB - The aim of this study was to examine the saturation patterns of cuprofane and polysulfone membranes in hemodialysis patients, and to correlate that with permeability of the alveolar membrane, unloading of CO2 over the membranes, and production of oxygen free radicals. Polysulfone membranes did not have the same desaturation pattern as the cuprofane membranes. Both membranes were equally effective in the unloading of CO2, and so alveolar hypoventilation does not explain oxygen desaturation during hemodialysis. White blood cells have a central role in the parallel development of early leucopenia and hypoxemia. The precise mechanism is still unknown because there were no changes in permeability of the alveolar membrane or production of oxygen free radicals. PMID- 8469794 TI - 4th International Sorrento Meeting on Current Therapy in Nephrology. May 31-June 3, 1992, Sorrento, Italy. Abstracts. PMID- 8469795 TI - A program evaluation of classroom data collection with bar codes. AB - A technology incorporating bar code symbols and hand-held optical scanners was evaluated for its utility for routine data collection in a special education classroom. A different bar code symbol was created for each Individualized Educational Plan objective, each type of response occurrence, and each student in the first author's classroom. These symbols were organized by activity and printed as data sheets. The teacher and paraprofessionals scanned relevant codes with scanners when the students emitted targeted behaviors. The codes, dates, and approximate times of the scans were retained in the scanner's electronic memory until they could be transferred by communication software to a computer file. The data from the computer file were organized weekly into a printed report of student performance using a program written with commercially available database software. Advantages, disadvantages, and costs of using the system are discussed. PMID- 8469796 TI - Delayed identity matching to complex samples: teaching students with mental retardation spelling and the prerequisites for equivalence classes. AB - Students with mental retardation learned delayed matching to sample in which some of the trials involved complex sample stimuli, each consisting of a picture and a printed word. A touch to the sample complex removed it from the computer display and produced either picture comparisons or a choice pool of letters. If the comparisons were pictures, selecting the picture identical to the preceding sample was reinforced. If the letters appeared, letter-by-letter construction of the preceding printed word sample was reinforced. The procedure engendered new constructed-response spelling performances to pictures and dictated words as samples. The emergence of relations among different sets of printed words (paired with the same pictures) suggested the formation of equivalence classes. One subject's data suggest that written spelling, oral spelling, and naming also may emerge as byproducts of the intervention. PMID- 8469797 TI - Establishing the manding function of communicative gestures with individuals with severe/profound mental retardation. AB - Procedures for teaching communicative gestures to individuals with mental retardation are focused mostly on establishing requesting or manding. It is often taken for granted that when a student has been taught to make a request, that he or she is indeed manding. Five students with severe/profound mental retardation accepted referents, regardless of whether the referents matched the gestures they made. Apparently, their responding could not be defined as manding. A correction procedure, including interruption, physical guidance, verbal instruction, and repetition, was then applied and increased the individuals' correct rejecting of unmatching referents. Data were collected within a multiple baseline design across individuals. It is suggested that assessing student's response when the trainer or teacher delivers items that do not match the referent of a prior request is a necessary part of each training program. PMID- 8469798 TI - Who is treated using restrictive behavioral procedures? A population perspective. AB - Considerable controversy surrounds the continued use of restrictive behavioral procedures in the treatment of destructive behaviors, such as self-injury, aggression, and property damage, displayed by some people with mental retardation. This study reports on the extent that pharmacological and behavioral consequences occur in response to these behaviors within a population of 31,000 people in one state's developmental services system. Data on these individuals are analyzed to determine the degree to which intellectual level, residential setting type, type and extent of problem behaviors, and age are related to the prescriptive use of pharmacologic and behavioral consequences. These variables appear to bear a significant relationship on the extent to which consequences are applied as part of treatment. Furthermore, although pharmacologic and several behavior consequences are applied at similar rates, it was found that generally timeout, as a specific treatment procedure, was applied at rates considerably less than those for psychoactive medication in each population sub-group that was examined. PMID- 8469799 TI - Evaluating and improving residential treatment during group leisure situations: a program replication and refinement. AB - The authors attempted to replicate and refine a program for evaluating and improving residential treatment services during group leisure periods in living units. In Study 1, an active treatment program was implemented using a consultant model in two living units serving persons with severe handicaps. Similar to previous research, the program was accompanied by decreases in nonadaptive client behavior in both units during leisure periods. In addition, a time-efficient monitoring system was developed which suggested that two staff-related variables, provision of leisure materials, and interactions with clients were related to the program's success. Study 2 evaluated more thoroughly the relationship of these variables to client nonadaptive behavior in 20 residential units in four states. Significant predictive relationships again were found between nonadaptive behavior and material availability, and between nonadaptive behavior and staff interactions with clients. Results of Study 2 also indicated that three living unit supervisors readily learned to use the evaluation system. Results are discussed regarding the importance of simple and efficient monitoring systems for routinely evaluating and improving residential services. PMID- 8469800 TI - Comparison of sight word training procedures with validation of the most practical procedure in teaching reading for daily living. AB - The effectiveness and efficiency (training trials and training errors through criterion) of stimulus fading, stimulus shaping, time delay, and a feedback only procedure were compared in teaching three adults with moderate developmental delays sight words encountered in activities of daily living. In Experiment 1, the four procedures were assessed during training in a controlled environment to identify the most effective and efficient procedure for each participant. All three adults acquired the target words, and the four procedures were found to be of comparable efficiency in total training sessions, whereas individual differences were found in training errors to criterion. In Experiment 2, the feedback only procedure was used to teach the three participants sight words in community settings. Participants learned new words in the community settings and used the previously trained words in daily living activities. The benefit of conducting a preliminary evaluation of instructional procedures during controlled training is discussed. PMID- 8469801 TI - Final report of the Bawnmore Personal Development Programme: staff attitudes and sexuality programme development in an Irish service organisation for people with mental handicap. AB - In this paper, issues on sexuality and mental handicap are reviewed, and recognition of the growing importance of sex education to integration is noted. The development of a sex education programme and staff training provided within a service organisation, with some involvement from other services within an Irish setting, are described, and their evaluation is reported. Attitudes towards involvement prove of particular interest, and factors influencing continuation or discontinuation are identified. The need for attitude change among staff and administration towards the priority given to sex education is highlighted, and a need for structural change in staffing arrangements to facilitate such education is indicated. Failure to recognise sexuality as a research issue in evaluating the success of integration efforts is noted, and such research is recommended as a top priority for the future. PMID- 8469802 TI - Out-of-home placement of children and adolescents with severe handicaps: behavioral intentions and behavior. AB - This study tracked the thoughts and actions regarding out-of-home placement in 100 families who had a child or early adolescent with severe handicaps. Parents' behavioral intentions regarding out-of-home placement were assessed using a single item measure of placement tendency (The Placement Tendency Index) four times over a total period of approximately 6 years. Statistical models used to predict time until placement indicated that the Placement Tendency Index had modest predictive capacity in the long run, but increased predictive utility over shorter periods. Closer examination of the movement of scores from one wave of data collection to the next revealed three patterns, indicating variability in the speed and direction with which parents move along the scale. PMID- 8469803 TI - Noncompliant behavior of people with mental retardation. AB - Literature pertaining to noncompliant behavior of people with mental retardation was reviewed. Noncompliant behavior was considered in terms of antecedents (characteristics of instructions), behaviors (characteristics of tasks being refused), and consequences (environmental results of noncompliance). Literature pertaining to nondisabled "oppositional" children was incorporated along with literature pertaining to persons with mental retardation. Research involving antecedent conditions suggested that noncompliance is more likely when instructions are vague and interrupted with other instructions. It also suggested that a series of high probability requests could enhance compliance to a subsequent low probability request. Research into behavior variables suggested that noncompliance is more likely when task demands are too difficult. Research into consequent conditions indicates that either positive or negative reinforcement may maintain noncompliant behavior. Treatment studies suggested that oppositional children respond poorly to verbal reward alone and somewhat better to tangible rewards and to programs utilizing timeout. By contrast, noncompliance by people with mental retardation appears to respond well to programs utilizing combinations of social and tangible rewards, but results also suggest that results of timeout programs are mixed. Implications for treatment were discussed along with suggestions for future research. PMID- 8469804 TI - [Reactive left ventricular hypertrophy: the functional and organic determinants of diastolic dysfunction (the therapeutic implications)]. PMID- 8469805 TI - [An analysis of the responses to the tilt-table test depending on the clinical characteristics of the syncopal episodes in patients without apparent cardiopathy]. AB - Seventy-six consecutive patients were evaluated to assess whether the response to head-up tilt test was related to the type of clinical presentation in patients with syncope of unknown origin and free from heart disease. The syncopal attacks were clinically characterized in a prospective fashion before the tilt test. In 44 patients (group I) syncope had been preceded by autonomic symptoms or was associated with recent or static sustained orthostatism. In 32 patients (group II), syncope had been sudden, without prodromal or autonomic symptoms. Mean age was 49 +/- 17 years in group I patients and 47 +/- 17 years in group II patients (NS). The degree of tilt was 75 degrees. During 30 min no drugs were administered, and then isoproterenol was infused for an additional 20 min (1-5 micrograms/min until a maximal heart rate of 140 bpm was achieved). Tilt test was considered as positive when the patient developed syncope or presyncope with hypotension. Tilt test was positive in 33 patients from group I (75%) and 12 from group II (37.5%)(p = 0.001). The positive response developed within the 30 initial min of the test (without isoproterenol infusion) in 19 of 33 patients from group I (57%) and in 3 of 12 patients from group II (25%) (p = 0.053). It is concluded that the response to tilt test is related to the clinical features of syncopal attacks. PMID- 8469806 TI - [The usefulness of continuous Doppler in the diagnosis of aortic coarctation]. AB - Were studied 32 patients with coarctation of the aorta by continuous wave Doppler ultrasound in order to assess the usefulness of this diagnostic method. Nineteen (59%) had native coarctation and 13 (41%) recoarctation. Seventeen (53%) were male and 15 (47%) female. The mean age when diagnosis was performed was 56 +/- 54 months. We found associated anomalies in 15 patients (46%). We studied 5 variables of the continuous Doppler curve at the descending aorta that were compared with those of a control group of 20 patients without cardiac anomalies. The variables were: peak systolic gradient (50.1 +/- 18 mmHg; VS 7.6 +/- 3 mmHg; p = 0.001); peak diastolic gradient 18.5 +/- 10 mmHg; VS 0.49 +/- 0.5 mmHg; p = 0.001; systolic velocity half time 151.5 +/- 40 msec; VS 102 +/- 17 msec; p = 0.01; diastolic velocity half time 132.2 +/- 82 msec; VS 7 +/- 14 msec; p = 0.001 corrected acceleration time (169 +/- 26 mmHg; VS 138 +/- 22 mmHg; p = 0.01). Systolic gradient was highly sensitive (100%) and specific (100%). Diastolic gradient and time to half peak diastolic velocity were very specific (100%) and less sensitive (93% and 62%). There were 6 false positive and 4 false negative when we used the time to half peak systolic velocity (sensitivity 81%, specificity 72%). We conclude that continuous Doppler is a useful method in the diagnosis of coarctation of the aorta. The most important variables of Doppler curve are systolic gradient, diastolic gradient and time to half peak diastolic velocity. All patients with coarctation of aorta had at least 2 variables altered. PMID- 8469807 TI - [The diagnosis of ventricular pseudoaneurysms. The complementary role of echocardiography, isotopic ventriculography and contrast ventriculography]. AB - The diagnostic yield of echocardiography, radionuclide ventriculography (first pass and multiple gated) and contrast ventriculography was evaluated in 11 patients in whom a diagnosis of left ventricular pseudoaneurysm had been made during the last ten years. The diagnosis was made by two dimensional echocardiography (associated with Doppler in the last 5 patients) in 8 of 11 patients (sensitivity: 73%). The major limitation of the technique, in addition to the impossibility of an adequate recording due to a suboptimal acoustic window, is the poor definition of the neck of the pseudoaneurysm, particularly in the inferior localization. By contrast, echocardiography is the only technique which permits the direct visualization of thrombi within the pseudoaneurysm. Multiple gated radionuclide ventriculography was diagnostic in 7 of 10 patients (sensitivity: 70%). Its major limitations are the poorer spatial resolution to visualize the pseudoaneurysm neck and the thrombi within the cavity. First pass radionuclide ventriculography was diagnostic in 4 of 6 patients (sensitivity: 67%). In one of them it improved on the diagnostic yield of the multiple gated technique. Contrast ventriculography was diagnostic in 5 of 7 patients (sensitivity: 71%). The diagnosis was missed due to technical problems in one patient and to significant thrombosis within the pseudoaneurysm in another. Thus, none of the imaging studies has optimal sensitivity. Therefore, all play a complementary role in the diagnosis of ventricular pseudoaneurysm. PMID- 8469808 TI - [Thrombolytic therapy in acute myocardial infarct. New performance protocols. Their influence on mortality and the incidence of complications]. AB - The new protocols of actuation in acute myocardial infarction thrombolysis have increased the number of patients treated, and have changed their characteristics. To assess the influence that this event has had in the complications incidence and mortality rate, we revise 704 infarcts treated with thrombolytic in a coronary unit, during 8 years. We separate two groups: 1) Patients treated since november 1983 to december 1988 following the established protocol at the beginning of this therapeutic (n = 328). 2) Patients treated since this date to july 1991, with a new protocol that include older than 70 years patients, moore than 6 hours of therapeutics delay and use of another thrombolytics, moreover streptokinase (n = 376). These changes have increased the number of thrombolysis in the second group (24.6 vs 49.1%; p < 0.001). Nevertheless being a higher group of risk we have found neither a significant mortality increase (6.40 vs 7.71%; p = NS), nor complications related to the thrombolysis: The incidence of major hemorrhages were 2.13 vs 1.06% (p = NS), cerebral hemorrhages 0.91 vs 1.6% (p = NS), hypotension related to the thrombolytics 15.55 vs 5.85% (p < 0.001). Neither has had significant difference in the incidence of reinfarcts (6.42 vs 5%; p = NS). In conclusion, the great number of thrombolysis realized nowadays, due to the actuation protocols changes, have increased significantly, neither the complications related with this therapeutic, nor the mortality rate, nor the reinfarcts number. PMID- 8469809 TI - [The identification of the best thrombolytic. Reflections on a problem without resolution]. PMID- 8469810 TI - [Cardiac arrhythmias (IV). Auricular flutter: its mapping and radiofrequency ablation]. PMID- 8469811 TI - [Coronary ostial stenosis after an aortic valve replacement diagnosed by transesophageal echocardiography]. AB - We submit the case of a 75-year-old man that underwent aortic valve replacement whose preoperative coronary angiography showed lesion-free coronaries. Two months after surgery he began to feel rapidly progressing effort angina pectoris. Transesophageal echocardiography showed prosthetic normal function while allowing the study of the great coronary trunks. We observed the presence of a 50% stenosis at the ostium of the left coronary artery trunk due to the use of selective coronary cannulation to supply cardioplegia solution during valve replacement. A second coronary angiography confirmed this finding. Transesophageal echocardiography may be used as an initial diagnostic method when coronary ostial stenosis is suspected after aortic valve replacement. PMID- 8469812 TI - [Percutaneous coronary transluminal angioplasty in a heart transplant recipient]. AB - A 46-year-old female, who underwent an orthotopic heart transplantation 5 years ago, presented an occlusive coronary artery disease with severe stenosis of the left anterior descending artery and a large septal perforator. An isonitrile scintigraphy showed a decreased uptake involving the anterior and inferior segments of the left ventricle. Percutaneous transluminal coronary angioplasty was successfully performed in both lesions. Three months after dilatation, improvement of the uptake in both myocardial segments was detected. The results of the percutaneous transluminal coronary angioplasty published in the literature are reviewed. PMID- 8469813 TI - [Anomalous origin of the right pulmonary artery from the ascending aorta. Its echo-Doppler diagnosis]. AB - The anomalous origin of the right pulmonary artery from the ascending aorta is a rare malformation. Its diagnosis and early surgical treatment are necessary to avoid its fatal outcome. We present the pulsed and color echo-Doppler findings in a patient with this pathology. PMID- 8469814 TI - [A right-to-left shunt through a patent foramen ovale without pulmonary hypertension]. AB - We report the case of a man 67-years-old with right-to-left shunt through a patent foramen ovale in absence of pulmonary hypertension. The contrast and transesophageal echocardiography showed significant right-to-left shunt and provided insight about the mechanisms that cause it. The aortic root was enlarged compressing the right atrium. Surgical repair was performed, the foramen ovale was closed and right atrial enlargement with a patch was carried out. Disappearance of the shunt was confirmed by means of transesophageal echocardiography in surgical-room. PMID- 8469815 TI - Whole-body plethysmography in the clinical assessment of infants with bronchopulmonary diseases. AB - Infant whole-body plethysmography offers a unique possibility of measuring end expiratory resting level (thoracic gas volume; TGV), and hence lung volume in its close interrelationship to airway function (airway resistance; R(aw), its reciprocal value, airway conductance, Gaw). Therefore, this technique is a valuable aid for objective evaluation of lung diseases in infants. This article gives an overview of the physiological background of this particular measuring technique and its usefulness in the clinical routine. Plethysmographic data obtained in infant survivors of the infant respiratory distress syndrome (iRDS), in infants with cystic fibrosis (CF) and in the so-called 'wheezy infants' are presented. Special emphasis is given to the fact that in such infants the interrelationship between changes in end-expiratory resting level and the deficit in airway mechanics is of great importance and, consequently, for the determination of functional lung derangement in each particular case of lung disease, both TGV and the closely related R(aw) and Gaw have to be evaluated. This recommendation has to be kept in mind when the different diagnostic tools for evaluation of treatment facilities are applied in this particular young age group of patients with lung disease. In children as in adult patients, inhalative treatment must be considered the mainstay of all therapeutic measures. However, in infants, the efficacy of such treatment regimens must first be evaluated by adequate functional investigations. Infant whole-body plethysmography offers one such possibility. PMID- 8469816 TI - Early and late follow-up of pulmonary embolism. AB - This study includes 61 patients referred with pulmonary embolism (PE) during 1 year. At admission, blood gas analysis, chest radiography and pulmonary lung scan were obtained in each patient; in a subset of patients pulmonary angiography was also performed to make the definitive diagnosis. Patients were treated with heparin and, later, with oral anticoagulants. Blood gas analysis, chest radiograph and perfusion lung scan were repeated 7, 30, 180 and 365 days after the diagnosis to evaluate the usefulness of these techniques in the follow-up of PE. Arterial hypoxemia and perfusion impairment recovered in parallel, both in the acute phase after embolism (7 days) and later up to 1 year. The great majority of recovery occurred within the first month after embolization. Radiographic signs compatible with PE tended to decrease early and disappeared almost completely after 30 days. Arterial blood gas analysis and perfusion scintigraphy detected 8 recurrences of PE that would be missed by chest radiograph. Arterial hypoxemia and the enlargement of descending pulmonary artery were positively correlated with the number of unperfused lung segments and, thus, may help predicting the severity of perfusion impairment in the acute stage. In conclusion, blood gas analysis and chest radiograph may be employed with or without perfusion lung scan to follow patients with PE up to 1 month after embolization; after that, only blood gas analysis and perfusion lung scan may give useful information about recovery from or recurrence of PE. PMID- 8469817 TI - Ovine tracheal muscle contraction in vitro: inhibition by calcium channel blockers gallopamil and verapamil. AB - We compared the inhibitory effects of calcium channel blockers, gallopamil and verapamil on acetylcholine (Ach)-induced contractions of ovine tracheal muscle in vitro. Adult sheep were sacrificed and tracheal strips were obtained by cutting the single tracheal rings from the mid-trachea. Tracheal strips were suspended in Krebs-Henseleit solution and isometric tension measured upon stimulation with cumulative doses of Ach (10(-7) to 10(-4) M) without and after pretreatment with gallopamil (10(-7) to 10(-6) M) or verapamil (10(-6) to 10(-5) M). In untreated tissues, the mean concentration of Ach required to produce 50% of maximal response (EC50) was 4.3 x 10(-6) M Ach. Both gallopamil and verapamil inhibited the Ach-induced contractions of ovine tracheal smooth muscle, by shifting the dose-response curves to Ach to the right. EC50 Ach for gallopamil (10(-6) M) and verapamil (10(-6) M) was 2.6 x 10(-5) and 5.2 x 10(-6) M, respectively. Dose ratio defined as postantagonist EC50 Ach/control EC50 Ach, was 7.7 for gallopamil and 2.0 for verapamil. Thus, the inhibitory effect of gallopamil was approximately 4-fold more potent than that of verapamil. Gallopamil was 17-fold more potent than verapamil in relaxing precontracted tracheal strips. The dose of calcium antagonists required to produce 25% relaxation (EC25) of tracheal strips precontracted with 10(-4) Ach was 3.7 x 10(-5) M for verapamil and 2.2 x 10(-6) M for gallopamil. These results indicate that gallopamil is effective against Ach induced contractions of ovine trachealis muscles, and is more potent than verapamil. PMID- 8469818 TI - Clinical and radiologic features, lung function and therapeutic results in pulmonary histiocytosis X. AB - Clinical appearance, radiologic findings, lung function and results of corticosteroid therapy were analyzed in 42 adult cases of biopsy-proven pulmonary histiocytosis X. Symptoms were present in only 64%. Using the ILO classification 1980, the evaluation of chest radiographs revealed all categories of profusion, size and shape of nodules. The characteristic 'ring figures', i.e. thin-walled cysts, in the parenchyma were detected in 78% of conventional tomographies (n = 27) and in all patients examined by CT (n = 5). In patients with early disease, lung function tests (n = 26) including body plethysmography, pulmonary diffusing capacity and ergospirometry revealed that parameters of gas exchange are most sensitive (TL,CO 84%, KCO 72%). Bronchial reactivity to carbachol was significantly higher than in controls (n = 12). Lung perfusion scintigram showed an abnormal, but uncharacteristic pattern in 81% (n = 26). During corticosteroid therapy, no progression was observed (n = 36). 85% of patients with radiographic evidence of progressive disease improved after administration of corticosteroids (n = 14). PMID- 8469819 TI - Multivariate analysis of factors affecting pulmonary function in bronchiectasis. AB - Impaired pulmonary function is of prognostic importance in bronchiectasis. To assess the factors affecting pulmonary function in bronchiectasis, we studied the clinical features, atopic status, bronchial responsiveness, systemic inflammatory indices, and sputum characteristics including volume, purulence, leucocyte count, neutrophil chemotactic activity, elastolytic activity (EA) and bacteriology in 82 Chinese patients. The majority of patients had impaired spirometry with airflow obstruction but normal carbon monoxide diffusing capacity. Multivariate analysis showed that factors significantly associated with worse lung function were: bronchial hyperresponsiveness, concomitant asthma, higher serum globulin, higher peripheral leucocyte count, lower serum albumin, greater sputum volume, diffuse disease and older age. When subjects with clinical asthma were excluded, similar factors were identified, and in addition, longer duration of disease, presence of eosinophils in sputum and higher sputum EA were significantly related to worse spirometry. Most of the identified factors reflect a state of inflammation. Thus the findings suggest that persistent inflammation plays an important role in the deterioration of lung function in bronchiectasis. PMID- 8469820 TI - Dobutamine, but not dopamine, augments the normal chronotropic response to acute hypoxemia. AB - Infusion of exogenous dopamine has been shown to alter both the hypoxic and the hypercapnic ventilatory response, but its effects on the hypoxic and the hypercapnic cardiac response have not been reported. The purpose of this study was to determine if cardiac responses to hypoxemia and hypercapnia are altered by infusion of either dopamine (DOP) or its analog dobutamine (DBT). Baseline mean arterial blood pressure (MAP) and heart rate (HR) were measured in 7 normal male subjects while normal saline was infused intravenously (NS1) for 30 min. Each subject then underwent both a eucapnic hypoxemic challenge (EHC), and a hyperoxic hypercapnic challenge (HHC). In a double-blinded randomized fashion either DOP1 or DBT1 was selected and infused at 5 micrograms/kg/min for 30 min. EHC and HHC were again performed. This sequence was then repeated following a second NS infusion (NS2) and the alternate vasopressor. On a second study day, the dose of dopamine (DOP2) selected was that sufficient to induce a similar rise in MAP as seen with DBT1. Following NS and DOP1 there was a reproducible significant linear increase in HR with progressive hypoxemia seen in all subjects. This response was significantly augmented following infusion of DBT1 (p < 0.03), but no such augmentation was noted with DOP2. No significant change in HR was noted during HHC. The mechanisms responsible for this augmentation of hypoxemic response during dobutamine infusion are unclear, and do not appear to be related to a rise in MAP. We speculate that it is due to an effect of dobutamine on beta 1-receptor activity. PMID- 8469822 TI - Computed tomography findings in idiopathic pulmonary hemosiderosis. AB - Computed tomography (CT) findings in a case of idiopathic pulmonary hemosiderosis (IPH) are presented. The contribution of this imaging modality to diagnosis is discussed. PMID- 8469821 TI - Diagnosis of pleural tuberculosis by detection of specific IgG anti-antigen 60 in serum and pleural fluid. AB - The objective of this study was the prospective evaluation of the IgG antibody levels to mycobacterial antigen 60 (A60) in serum and pleural fluid and their role in the diagnosis of tuberculous pleuritis. The level of IgG was measured by Elisa in 30 patients with tuberculous pleuritis and 48 control subjects with pleural effusion (24 with carcinoma, 10 with transudative pleural effusion, 11 with empyema or parapneumonic effusion, 1 with pulmonary embolism and 2 due to systemic lupus erythematosus). The median titers of IgG against A60 of both serum and pleural fluid from tuberculous patients [445.6 +/- 133.56 and 263 +/- 72.58 Elisa units (EU) respectively] were significantly higher than those of corresponding median values (97.3 +/- 8.35 and 41.3 +/- 4.93 EU) of the control group (p < 0.01 and p < 0.01, respectively). Considering 240 units as cutoff point for a positive test in serum, the sensitivity was 53.3% and the specificity 100%. In the pleural fluid the cutoff point value was established at 150 units, with a sensitivity of 50% and specificity of 100%. We concluded that Elisa using A60 is a reliable and rapid test with an acceptable sensitivity and magnificent specificity. PMID- 8469823 TI - From not detected pulmonary embolism to diagnosis of chronic thromboembolic pulmonary hypertension: a retrospective study. AB - The past and present clinical history of 13 patients with hemodynamic and angiographic diagnosis of chronic thromboembolic pulmonary hypertension (CTPH) was reviewed in order to investigate the reasons for failure of resolution of acute pulmonary embolism (PE) and findings useful for diagnosis of CTPH. All patients had chest radiograph, ECG, arterial blood gas analysis and pulmonary perfusion scintigraphy performed. Clinical assessment demonstrated that no patient had diagnosis and treatment of the several retrospectively identified episodes of PE (from 1 to 8); the lack of diagnosis was due to underestimation of symptoms and signs such as dyspnea (85%), pleuritic chest pain (31%) or phlebitis (46%) that were present months or years earlier. Alternative diagnoses erroneously made were dyspnea of unknown origin (5 cases), left heart failure (4 instances) and pneumonia (2 cases). Once CTPH has developed, chronic dyspnea (92%) and substernal chest pain (100%) are almost always present: chest radiograph and ECG show signs of chronic hypertension such as enlargement of hila (100%), right heart sections (77%), azygos vein (46%) and P pulmonale (67%), T inversion on right precordial leads (75%), S-T segment depression (75%), respectively. Perfusion scintigraphy shows severe perfusion impairment (55.7% of the total vascular bed) paralleled by severe hypoxia (standard PaO2 = 49 +/- 14.1 mm Hg). In conclusion, patients with PE who develop CTPH are not diagnosed and thus untreated because clinical symptoms and signs of acute PE have not been recognized. If CTPH develops, clinical assessment (including simple and noninvasive techniques such as chest radiograph, ECG and blood gas analysis) may show a quite characteristic pattern useful for diagnosis. PMID- 8469824 TI - [Fibrosis and fusion of the heart valve]. PMID- 8469825 TI - [Myocardial hypertrophy and fibrosis]. PMID- 8469826 TI - [Fibrosis of myocardium after myocardial infarction]. PMID- 8469827 TI - [Myocardial fibrosis in post-myocarditis]. PMID- 8469828 TI - [Analysis of respiratory pattern during exercise by respiratory rate-tidal volume relationship in healthy subjects]. PMID- 8469829 TI - [Signal-averaged electrocardiogram in right bundle branch block patients after surgical repair for congenital heart disease]. AB - Right bundle branch block (RBBB) type was investigated using signal-averaged electrocardiogram (SAECG) in 35 RBBB patients after surgical repair of ventricular septal defect and tetralogy of Fallot. The type of RBBB was first identified by body surface mapping; 12 patients had proximal RBBB, and 23 had peripheral RBBB. The control group consisted of 20 healthy volunteers. The following three findings were seen in most patients with proximal RBBB, and were useful for determining the type of RBBB; a filtered QRS duration equal to or longer than 160 msec, a fragmented signal number equal to or greater than 10 and the whole type of filtered QRS pattern. The sensitivity and specificity of SAECG for proximal RBBB were shown to be high. In conclusion, SAECG was found to be useful for non-invasive determination of RBBB types. PMID- 8469830 TI - [The efficiency of continuous hemofiltration/hemodialysis for acute respiratory failure complicated with acute renal failure]. AB - Continuous hemofiltration/hemodialysis (CHF/CHD) have emerged as effective modalities in the management of acute renal failure. More recently, these therapies have received attention for non-renal application such as adult respiratory distress syndrome (ARDS) and multiple organ failure. To assess the potential benefits of CHF/CHD in the management of severe impairment of pulmonary gas exchange, we evaluated a series of clinical variables in a group of patients with acute respiratory failure complicated with acute renal failure. In 9 of 15 patients, pulmonary gas exchange was improved. Intrapulmonary shunt (Qs/Qt) and pulmonary vascular resistance were also improved during the therapies. The beneficial effects of the modalities seems to be induced by effective removal of extravascular lung water. However, the fact that the same effects were also observed in a few patients with zero or positive fluid balance may indicate the possibility of elimination of circulating middle-molecular pulmonary toxic mediators. We concluded CHF/CHD are recommendable methods for the management of acutely ill patients with respiratory failure. PMID- 8469831 TI - [The microcirculatory dynamics of prostaglandin E1 and/or nicardipine and their different reactions in the hyper- and hypodynamic state of septic shock in a rat model]. AB - The reactions of the mesenteric microcirculation dynamics to prostaglandin E1(PGE1) and nicardipine were investigated under continuous biomicroscopy with a high speed video analyzer in septic shock models using rats. Both of the drugs induced similar reactions. In the hyperdynamic state, the vasodilation and increasing velocity of red blood cells (RBC) stimulated by both of these vasodilators were similar to those in normal control state. However, in the hypodynamic state the vasodilators especially PGE1 had little effect on increasing the velocity of RBC in spite of their vasodilating action. Therefore these vasodilators are useful in order to improve the microcirculatory blood flow in states such as early septic-shock state. PMID- 8469832 TI - [A case of chronic recurrent pulmonary embolism complicated with effort angina pectoris]. AB - A 50-year-old man was admitted to our hospital because of shortness of breath and an oppressive feeling in his chest on exertion. As a result of examinations including pulmonary-angiography, pulmonary perfusion scan and phlebogram, we diagnosed the case as chronic recurrent pulmonary embolism due to deep vein thrombosis. Later on, the patient showed an abnormal reaction on treadmill exercise test, and revealed redistribution at the anteroseptal and the inferior wall on thallium exercise test. We performed coronary angiography and diagnosed the case as angina pectoris (seg. 1 was total occlusion, segs. 2 and 3 were filled with bridge collateral, seg. 7 was 75% stenotic lesion). We evaluated the acute effect of vasodilators on pulmonary and systemic hemodynamics. The effect was beneficial in that it improved the hemodynamics. On account of this we thought a reversible condition was presented, and we administered these drugs to this patient. PMID- 8469833 TI - [Activation of coagulation and fibrinolysis in patients with abdominal true aortic aneurysm associated with disseminated intravascular coagulation]. AB - Two cases of abdominal true aortic aneurysm (AAA) associated with disseminated intravascular coagulation (DIC) were reported. Case 1 was an 81-year-old male who was admitted because of hematoma on the left leg and in whom was found by MRI an aortic aneurysm of 14 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia, hypofibrinogenemia and increased level of FDP. DIC was well controlled by surgical repair of the aneurysm after the administration of a small dose of heparin. Case 2 was a 60-year-old male who was admitted because of lumbago and hematoemesis and in whom was found by CT and echography an aortic aneurysm of 5.5 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia and an increased level of FDP. On the 2nd hospital day, he suddenly died due to the rupture of the aortic aneurysm. In most of 9 cases with AAA without DIC, plasma levels of thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex and FDP-D dimer were also elevated. These findings indicate that the coagulation and fibrinolysis systems were generally activated in patients with AAA, and that DIC tends to occur in patients with a giant aortic aneurysm or an impending ruptured aneurysm. PMID- 8469834 TI - [The efficacy of external high frequency oscillation: experience in a quadriplegic patient with alveolar hypoventilation]. AB - External high frequency oscillation (EHFO) around a negative pressure using a thoracoabdominal chamber without an artificial airway has been shown to be an effective form of ventilation in a quadriplegic patient. The patient was an 18 year old male, suffering from high-level cervical cord tumor (lipoma). His respiratory distress was severe, respiration was diaphragmatic only. Because of acute respiratory insufficiency, he was intubated and put on IPPV. Attempts at weaning were not thought to be feasible. Then the Hayek Oscillator was applied with a frequency of 120. After 5 days on the Hayek Oscillator, he was extubated. EHFO was associated with a significant increase in PaO2 and VA, and a significant decrease in PaCO2. It is remarkable that the patient expelled sputum whenever he was connected to the Hayek Oscillator, far beyond that achievable by physiotherapy. EHFO avoids the need for endotracheal intubation, thus reducing the hazards of mechanical ventilation attributable to intubation. We conclude that EHFO produces gas exchange significantly and that this technique may have potential clinical application. PMID- 8469835 TI - [A case of a patient with sternocostoclavicular hyperostosis complaining of severe chest pain, which must be distinguished from cardiovascular disease]. AB - We report a case of a patient complaining of severe chest pain which required a differential diagnosis between cardiovascular disease and sternocostoclavicular hyperostosis. The patient was a 61-year old male who began experiencing pain across both scapulas at the end of September, 1990. He was admitted to our hospital when the pain extended to the back and anterior chest areas. Examination on admission revealed inflammation with a white blood cell count at 11,800/mm3, an erythrocyte sedimentation rate of 136 mm/hr, and CRP at 14.2 mg/dl. Angina pectoris was suspected based on findings from coronary arteriography which showed 60% stenosis at Seg 6. A Ga-scintigram conducted to determine the cause of the chest pain revealed accumulations in the upper mediastinum. CT and MRI both showed hyperostosis of the sternum, and bone scintigram confirmed marked accumulations in the same area. Palmoplantar pustulosis (PPP) was also clearly noted on the palms and soles of the feet. Sternocostoclavicular hyperostosis was diagnosed based on these findings. Sternocostoclavicular hyperostosis was suspected in this case based on the clinical findings, inflammatory state, and accumulations revealed by bone scintigraphy. However, the diagnosis could have been more conclusive if non-suppurative hyperosteostic osteomyelitis were observed by bone biopsy. A differential diagnosis for unknown sources of chest pain should be considered in cases such as this. PMID- 8469836 TI - [A study of myocardial disorders in an autopsy case of mitochondrial encephalomyopathy]. AB - We report an autopsy case of a 19 year-old man with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) a subgroup of mitochondrial encephalomyopathy presenting cardiomyopathy. He had repeatedly suffered from transient unconsciousness, hemiplegia, hemianopsia and convulsion attacks since the age of 9, and he died of severe congestive heart failure. In laboratory findings, blood lactate and pyruvate were markedly increased. Skeletal muscle biopsy demonstrated numerously scattered ragged-red fibers with modified Gomori's trichrome staining. Enzymatic activities of the mitochondrial respiratory chain showed a marked decrease of NADH cytochrome c reductase (complex I). In postmortem examination, the heart was 310g in weight and had right ventricular dilatation. Microscopically, degenerated and scattered myocardial cells (ragged-red fibers), interstitial edema and microvascular hyperplasia were demonstrated in the myocardium. Under the electron microscope, abnormal mitochondria proliferated and myofibrils were unusually sparse. Immunohistochemical studies with specific antibodies against the mitochondrial electron transfer enzyme subunits revealed a reduction of immunoreactive materials for complex I in the myocardium. These results suggested the relationship of myocardial disorders and decreased activity of complex I in electron transfer enzymes in this patient. PMID- 8469837 TI - [Two cases of idiopathic ventricular fibrillation with interesting electrocardiographic findings]. AB - We encountered two cases of ventricular fibrillation (VF) without overt heart disease. The first case we report is that of a 47-year-old man, and the second case is a 39-year-old man. VF occurred in the night unrelated to myocardial ischemia or myocarditis. Their basic ECGs showed normal sinus rhythm, but neither QT prolongation nor abnormal Q wave was seen. But we could see IRBBB and ST segment elevation in the V1-2 lead not only in the acute phase, but also in the chronic phase. Abnormal findings were not found in noninvasive cardiac examinations, nor in cardiac catheterization and histological examinations. In the second case, VF was induced by electrical stimulation, and Disopyramide was found to be effective for the prevention of VF. The patient in the first case died suddenly two years after his first attack. Both cases have interesting ECG findings, and it may be that they play on important role in discovering the etiology of sudden cardiac death. PMID- 8469838 TI - [A case of dextrocardia concomitant with tetralogy of Fallot, patent ductus arteriosus and bronchiectasia]. AB - We report a case of dextrocardia concomitant with tetralogy of Fallot (TOF), patent ductus arteriosus (PDA), bronchiectasia, and pulmonary tuberculosis. A 24 years-old man without surgical operation for TOF, whose diagnosis had been made at infancy, was admitted to the Osaka City University Hospital because of massive hemoptysis. The diagnosis of pulmonary tuberculosis was made. He received anti tuberculotic drugs and bronchial arterial embolization improved his symptoms. A case of mirror-image dextrocardia concomitant with TOF, PDA, and bronchiectasia, as seen in our case, has a low incidence rate, and, moreover, such a case concomitant with pulmonary tuberculosis is rarer still. PMID- 8469839 TI - [Partial anomalous pulmonary venous connection to inferior vena cava (incomplete type of scimitar syndrome) in an elderly patient]. AB - A 71-year-old woman presented with recent onset of dyspnea and fatigue on moderate exertion. She had been well during her entire life and had had three pregnancies and deliveries. Cardiomegaly was noted at the age of 30. On physical examination, systolic murmur was detected at the lower left sternal border. The chest X-ray showed cardiomegaly, increased pulmonary vascular markings and elevated right diaphragm. The electrocardiogram showed left ventricular hypertrophy. The echocardiography showed enlargement of right ventricle and atrium, massive tricuspid regurgitation and anomalous venous flow connected to the inferior vena cava from its right-posterior side. Cardiac catheterization demonstrated mild pulmonary hypertension and O2 step-up at the level of the anomalous venous connection to the inferior vena cava. On pulmonary arteriography, left pulmonary venous flow return to the left atrium and atrial septal defect was not found. Veins from the right lung met to form one vessel, went downward, and connected to the inferior vena cava at the level of Th12. L-R shunt was 45% and Qp/Qs was 1.83. Isolated partial anomalous pulmonary venous connection is a rare finding, and it is thought that the natural prognosis is good. The existence of our case, diagnosed at the age of 71, supported this concept. PMID- 8469840 TI - Microemboli reduce phase III slopes of CO2 and invert phase III slopes of infused SF6. AB - We investigated the effect of increasing doses of intravenously infused glass microspheres (mean diameter 125 microns) on gas exchange in anesthetized, heparinized, mechanically ventilated goats (VT = 16-18 ml/kg). Breath-by-breath CO2 expirograms were collected using a computerized system (Study A) during the infusion of a total of 15 g of microspheres. We found a 50% decrease in extravascular lung water by indicator dilution with a corresponding doubling of alveolar dead space (VDalv). Airways deadspace (VDaw) decreased by 13 ml (10%) and mean normalized phase III slope for CO2 decreased from 0.23 to -0.08 L-1 becoming negative in 3 of 5 animals. In a second study (Study B), simultaneous breath-by-breath CO2 and infused SF6 expirograms were collected using an infrared CO2 analyzer and a mass spectrometer. Under baseline conditions VDaw for CO2 was smaller than for SF6 and the ratio of the phase III slope for SF6 to the phase III slope for CO2 was 1.39. Following embolization there were no differences in VDaw between the two gases, however, the phase III slope for CO2 became either slightly negative or extremely flat, while the phase III slope for SF6 became negative in 73% of the breaths (-0.17 L-1, P < 0.05). Negative phase III slopes have been predicted by a single path model when blood flow is confined to the most mouthward generations of the acinus (Schwardt et al., Ann. Biomed. Engin, 19: 679-697, 1991). The agreement between the numerical model and the experimental data is consistent with a serial distribution of blood flow within the acinus. PMID- 8469841 TI - Effects of hypobaria on parabronchial gas exchange in normoxic and hypoxic ducks. AB - Cardio-respiratory parameters and air sac and blood gases were measured in the unrestrained, unanesthetized duck during exposure to normobaric (PB = 746 Torr) or hypobaric (PB = 253 Torr) normoxia (PIO2 = 143 Torr) and hypoxia (PIO2 = 41.5 Torr). Compared with normobaria at the same PIO2, hypobaria caused a statistically significant increase in ventilation during both normoxia and hypoxia, resulting in elevated PO2 and diminished PCO2 in the caudal thoracic and clavicular air sac, and in increased PaO2 and decreased PaCO2. Similarly, lactic acid production was elevated in hypobaria, and the resulting decrease in arterial pH may be responsible for the increase in ventilation. Despite these changes, there was no evidence for altered gas exchange efficiency during hypobaria. This suggests that no significant diffusion limitation is present in the air capillary gas phase in normobaria, that could have been diminished with hypobaria. It also suggests that the aerodynamic valving efficiency, present during inspiration at the level of the medioventral bronchi, is not affected by hypobaria. Although the mechanisms underlying the increased lactic acid production and ventilation are not understood, they may exert an advantageous effect on high altitude tolerance of the bird. PMID- 8469842 TI - Regional lung impedance from forced oscillations through alveolar capsules. AB - We developed a technique for applying forced oscillations in flow between 5 and 200 Hz to the lung through an alveolar capsule. This provided measures of the complex alveolar input impedance of the lung, which we modelled in terms of an elastic alveolar unit connected to the rest of the lung by a peripheral airway. The estimated elastance of the alveolar compartment in 6 normal dogs was about 5 orders of magnitude greater than the elastance of the entire lung. The resistance of the airway leading into the compartment from the rest of the lung was about 5 orders of magnitude greater than the resistance of the entire airway tree. The capsule oscillation technique thus gives mechanical information about an extremely small region of the lung (in the order of 10 mm3 in volume) just under the capsule. A bolus i.v. injection of methacholine caused a variable response in the alveolar regions studied, with some regional elastances and resistances increasing while others decreased, despite the fact that overall lung resistance and elastance always increased. We conclude that our capsule oscillator technique yields precise mechanical information about very small distal regions of the lung, and that these regions respond heterogeneously to injected methacholine. PMID- 8469843 TI - Differential function of the costal and crural diaphragm during emesis in canines. AB - In six mongrel dogs under thiopental anesthesia, piezoelectric transducers and bipolar electromyographic (EMG) wires were installed onto left costal, medial crural and lateral crural segments of the diaphragm. During CO2 rebreathing, shortening and EMG activity increased significantly in all three regions of the diaphragm compared to resting breathing. During emesis, (1) both shortening and EMG activity significantly increased compared to resting in costal segment; however, (2) lateral crural shortening was not increased in spite of significant increase in EMG activity; furthermore, (3) the medial crural segment lengthened without any increased EMG activity. These results demonstrate a differential recruitment of costal and crural diaphragm segments, and an additional differential activity within the crural segment between medial and lateral crural regions, during emesis. This activity of the canine diaphragm is consistent with a central influence of emesis upon individual regions of the diaphragm. PMID- 8469844 TI - Thin-fiber phrenic afferents mediate the ventilatory response to diaphragmatic ischemia. AB - We assessed the role of groups III and IV phrenic afferents in the ventilatory response to diaphragmatic ischemia in mechanically ventilated, chloralose anaesthetized dogs using the in-situ isolated and innervated left hemidiaphragm preparation. The inspiratory motor drive to the right (Rt Edi) and left (Lt Edi) diaphragms, parasternal (Eps), and alae nasi (Ean) muscles was measured from the peak integrated EMG activities. When left diaphragmatic ischemia was produced in the control group (n = 6) by occluding the left phrenic artery for 20 min, LtEdi increased to 158%, RtEdi to 160%, Eps to 150% and Ean to 135% of baseline values. Left diaphragmatic tension, however, remained unchanged during the ischemia period. In the capsaicin-treated group (n = 6), we injected repeated doses of capsaicin, a selective stimulant of groups III and IV afferents, into the left phrenic artery to eliminate inputs from these afferents. Repeated injections of capsaicin are known to induce prolonged periods of afferent dysfunction. The first two injections of capsaicin (1 mg each) produced transient activation of the inspiratory muscles and higher breathing frequencies. Subsequent injections, however, failed to elicit any ventilatory changes. When diaphragmatic ischemia was induced after the last injection of capsaicin, no changes in the Right Edi, Eps and Ean were observed, whereas Left Edi and left diaphragmatic tension declined significantly. We conclude that increased inspiratory motor drive during selective diaphragmatic ischemia is mediated through the activation of groups III and IV phrenic afferents. PMID- 8469845 TI - Role of muscle perfusion and baroreception in the hyperpnea following muscle contraction in dog. AB - The influence of impeding muscle perfusion on the time course of ventilatory decline during recovery from electrically induced hindlimb contractions has been studied in 14 anesthetized dogs. When intravascular balloons, placed in abdominal aorta and inferior vena cava just rostral to the iliac bifurcation, were inflated at the cessation of contraction bout, minute ventilation (VE) was significantly reduced during recovery compared with control. The subsequent restoration of iliac circulation rapidly augmented VE, which peaked at the fifth breath after release, by an average of +4.97 L.min-1; VE then returned exponentially to resting (pre-contraction) level. Breathing 100% O2 did not affect the VE recovery pattern neither during iliac occlusion nor immediately after its release (the peak average delta VE = +4.42 L.min-1). When a local anesthetic (5% Lidocaine) was applied bilaterally to the regions of carotid bifurcation, systemic blood pressure was significantly increased and the VE response to both iliac occlusion and release were nearly abolished. The VE response to inhalation of 5% CO2 in air was not affected by this procedure, whereas the stimulation of VE with 2 mg i.v. bolus of NaCN was attenuated. When the local anesthetic was thoroughly washed out (and systemic blood pressure had returned to control level) the previously observed VE responses to iliac occlusion and release were restored. These results and analysis of the VE response timing (transits and latencies) suggest that the vascular rather than humoral effects or tissue 'metaboreception' modulate ventilatory recovery from muscular contractions; baroreception appears to be important in this process. PMID- 8469846 TI - Influence of prolonged adenosine receptor blockade on fetal sleep and breathing patterns. AB - Chronically prepared fetal sheep were subjected to 48 h infusions of theophylline, an adenosine antagonist, enprofylline, a xanthine without adenosine antagonism, or saline. Theophylline increased mean (+/- SD) incidence of REM sleep from 49.3 +/- 8.3% to 57.3 +/- 6.7% (p < 0.02) and wakefulness from 1.3 +/- 1.4% to 8.1 +/- 7.1% (p < 0.01). On the first day of theophylline infusion incidence of fetal breathing (FB) increased from 37.9 +/- 8.1% to 53.7 +/- 11.6% of total time (p < 0.002) and from 76.4 +/- 10.2% to 87.6 +/- 10.3% of REM sleep (p < 0.02). Diaphragmatic EMG/min increased from 6.9 +/- 4.0 to 17.3 +/- 13 arbitrary units (p < 0.02). By the second day of infusion, FB had returned to baseline value. Enprofylline and saline had no effect. 125 micrograms phenyl isopropyl adenosine (PIA) i.v. caused fetal apnea that was reduced from 143 +/- 45.5 min on the control day to 39.8 +/- 34.7 min (p < 0.001) during theophylline infusion. Enprofylline and saline had no effect, suggesting that the observed theophylline effect was due to its adenosine antagonism rather than to non specific xanthine action. We conclude that endogenous adenosine suppresses FB, but since theophylline did not alter the basic relationship between FB and REM sleep it is not primarily responsible for apnea during NREM sleep. PMID- 8469847 TI - Effects of halothane and isoflurane in the upper airway of dogs during development. AB - It has been previously found that volatile anesthetics significantly affect the activity of laryngeal receptors. In this study we have investigated the respiratory effects of these volatile anesthetics delivered into the upper airway of newborn and adult dogs. Experiments were performed on 17 5-14-day-old, 3 26-28 day-old and 3 adult dogs, anesthetized and breathing spontaneously through a tracheostomy. In the youngest age group, halothane decreased ventilation (VE) to 37.6 +/- 6.8% of control (mean +/- SE; P < 0.01) due to a decrease in both frequency and tidal volume. Peak inspiratory and expiratory flows, and esophageal pressure (Pes) were depressed also (60.8 +/- 6.5%, 51.6 +/- 7.1% and 66.5 +/- 8.1% of control, respectively; P < 0.01). Superior laryngeal nerve (SLN) section abolished the changes in VE, but residual significant decreases in peak flows and Pes were still present and disappeared only after topical anesthetization of the nasal cavities. Isoflurane had similar but weaker effects on VE (74.2 +/- 2.8% of control; P < 0.01), accompanied by a decrease in peak inspiratory and expiratory flows and Pes. SLN section abolished these changes. In the 26-28 day age group there was only a decrease in peak inspiratory airflow with the halothane challenge; isoflurane did not have any effect. In the adult dogs halothane caused only a marginal decrease in inspiratory time. The depressive effects of halothane and isoflurane should be considered when they are used for induction of anesthesia in newborns. PMID- 8469849 TI - Hematologic responses and the early development of hypoxic pulmonary hypertension in rats. AB - We have previously described the development of greater right ventricular hypertrophy after 7 days of hypoxia in the altitude-susceptible H strain compared to the resistant M strain of Sprague-Dawley rat. Greater polycythemia also occurs in the H strain after 2-3 weeks of hypoxia and is characterized by increased mean red cell volume (MCV), reticulocyte count (Retic), and blood viscosity after 4 weeks of hypoxia. In the present study, we determined the time course of development of these hematologic responses, whether differences in MCV are associated with differences in red cell deformability, and whether the hematologic differences might contribute to the early cardiopulmonary differences between the strains. We found that although hematocrit (Hct) did not differ between the strains until 21 days of hypoxia, MCV and Retic were greater in the H strain after only 3 days and whole blood viscosity was greater after 7 days. However, no differences in the viscosity or deformability of reconstituted red cells (Hcts 10% and 25%) were apparent at any time during hypoxic exposure. Furthermore, pressure-flow curves obtained using blood and lungs isolated from 7 day hypoxic rats suggested that the largest component of pressure elevation in the H rats was related to pulmonary vascular rather than hematologic factors. We conclude that although H rats have exaggerated hematologic responses to hypoxia, differences in pulmonary vascular structure and tone are more likely to be responsible for the strain differences in cardiopulmonary responses occurring after 7 days of hypoxia. PMID- 8469848 TI - Effects of halothane, enflurane, and isoflurane on laryngeal receptors in dogs. AB - The effects of halothane, enflurane, and isoflurane on laryngeal receptors were investigated in 6 anesthetized dogs breathing spontaneously through a tracheostomy. Single unit action potentials were recorded from the peripheral cut end of the superior laryngeal nerve (SLN) while different concentrations of volatile anesthetics (1.25, 2.5, 5.0%) were administered in the expiratory direction at a constant air-flow (6 l/min) for 1 min through the functionally isolated upper airway. A total of 21 respiratory-modulated mechanoreceptors, 18 "irritant" receptors, and 7 cold receptors were studied. The overall results obtained from the 16 respiratory-modulated mechanoreceptors challenged with the 3 anesthetic gases disclosed a prevalent inhibitory effect and halothane proved to be the most effective of the 3 gases. The activity during both the inspiratory and expiratory phase was significantly reduced only by halothane (inspiratory phase, P < 0.01; expiratory phase, P < 0.05), while neither isoflurane nor enflurane caused significant changes in receptor activity. Of the 18 irritant receptors, 14 receptors increased their activity in a dose-related manner in response to one or more of the anesthetics although the effect of halothane was more pronounced than those of enflurane and isoflurane. All of the 7 cold receptors consistently increased their activity in a dose-related manner in response to halothane whereas 3 of 7 receptors were insensitive to enflurane and 4 of 7 receptors were insensitive to isoflurane. Our results indicate that, while all three commonly used anesthetics can have an effect on different types of laryngeal receptors, the effects of halothane are more pronounced than those of the other two gases in terms of changes in receptor activity. PMID- 8469850 TI - Exogenous erythropoietin fails to augment hypoxic pulmonary hypertension in rats. AB - In two rat strains (H and M) with differing susceptibilities to chronic hypoxia we examined the role of polycythemia in the differing hypoxic pulmonary hemodynamic responses. We hypothesized that augmentation of hematocrit (Hct) during hypoxia in the resistant M strain would render cardiopulmonary responses similar to those obtained in the susceptible H strain. Administration of human recombinant erythropoietin (EPO) in doses of 100, 250 and 500 U.kg-1 s.c. thrice weekly for three weeks raised Hct similarly in both strains indicating that normoxic rats had similar sensitivities to EPO. In rats exposed to hypobaric hypoxia (0.5 atm) for 21 days, EPO (500 U.kg-1 thrice weekly) significantly increased Hct and whole blood viscosity as expected. Surprisingly, right ventricular (RV) to body weight (BW) ratio as an index of right ventricular hypertrophy (RVH) and RV peak systolic pressure did not increase in EPO-injected rats of either strain compared to hypoxic controls. Among hypoxic animals, Hct correlated highly with viscosity but not with RV/BW. We conclude, contrary to our hypothesis, that polycythemia does not appear to be responsible for the strain difference in RVH and pulmonary hypertension. PMID- 8469851 TI - Haemoglobin function in intact Lampetra fluviatilis erythrocytes. AB - The red cell pH as a function of oxygen saturation of haemoglobin and the oxygen affinity of haemoglobin as a function of red cell pH in Lampetra fluviatilis were studied at intracellular pH values ranging from 6.7 to 8.0. The maximal increase in red cell pH upon deoxygenation, 0.326 units, was seen when the pH of oxygen saturated erythrocytes was 7.7, a value corresponding to the red cell pH of resting lampreys. The effect of oxygen saturation on red cell pH was reduced both when the red cell pH was decreased and when it was increased. The haemoglobin oxygen affinity was strongly pH-dependent, with a Bohr-factor of -1.03. At a high pH (7.67) maintained by lamprey red cells at physiological conditions, the P50 value was 28.2 Torr. At a pH value (7.33) similar to that of rainbow trout, the P50 value was 73 Torr. Thus, the high red cell pH in lamprey is required for effective oxygen loading in gills. It also maximizes the apparent cooperativity of oxygen binding. PMID- 8469852 TI - Signal transduction in smooth muscle cells from human airways. AB - The aim of this study deals with the post-receptor events involved in the response of cultured smooth muscle (SMC) from human bronchi to various agonists of the contraction. [3H]inositol phosphates (IPs) were isolated by high performance liquid chromatography (HPLC) and intracellular Ca2+ concentration ([Ca2+]i) was determined with the Fura-2 fluorescence technique. Following 5 sec stimulation with histamine, an elevation of several [3H]IPs, in particular [3H]1,4-IP2, [3H]1,4,5-IP3 and [3H]1,3,4,5-IP4, above the control values was observed. Following an incubation of 10 or 15 sec with histamine, the content of [3H]1,4,5-IP3 declined towards its basal value, while the amount of metabolites ([3H]4-IP, [3H]1,4-IP2, [3H]1,3,4-IP3) increased with time; [3H]1,3,4,5-IP4 varied little between 5 and 10 sec and decreased at 15 sec. SMC responded also to carbachol and to prostaglandin F2 alpha (PGF2 alpha) by an enhanced production of [3H]IPs, whereas neurokinin A (NKA) had no effect on the turnover of [3H]IPs. Histamine, carbachol and PGF2 alpha evoked a transient elevation in [Ca2+]i, followed by a sustained increase. The duration of the transient elevation appeared similar to that of the increase in [3H]1,4,5-IP3. These results suggest that the 'phospholipase C-1,4,5-IP3-Ca2+ release' signalling pathway is involved in the physiological response of human airway SMC to histamine, carbachol and PGF2 alpha. PMID- 8469853 TI - Effect of acute hypoxia on metabolism and ventilation in awake piglets. AB - We studied the effect of acute sustained hypoxia on ventilation (VE) and oxygen consumption (VO2) over one hour during quiet wakefulness in young (6 days) and older (6 weeks) piglets in thermoneutral conditions during baseline, moderate hypoxia (PaO2 approximately 45 mmHg), and severe hypoxia (PaO2 approximately 30 mmHg). During severe hypoxia, ventilation and pH increased while PaCO2 decreased in both age groups. Blood gas changes (decreases PACO2, increases pH), but not ventilatory changes, were greater in the older piglets (P < 0.05). VO2 decreased similarly (-30%) while VE/VO2 rose over 160% in both age groups. During moderate hypoxia, changes in blood gas, VE, and VO2 were in a similar direction, but smaller in magnitude. We conclude that: (1) changes in blood gases and VO2 are amplified by maturation and severity of hypoxia and (2) blood gas changes are greater in older vs young piglets despite similar ventilatory responses suggesting maturational differences in CO2 production or dead space ventilation. PMID- 8469854 TI - Measurement of solute fluxes in isolated rat lungs. AB - Most previous studies in isolated perfused lungs have utilized measurements of solute flow from alveolar to vascular space to characterize the barrier and transport properties of the alveolar epithelium. In this study, we measured flux of a series of nonionic hydrophilic solutes and sodium across the alveolar epithelium of the isolated rat lung from perfusate to airspace (P-->A), as well as from airspace to perfusate (A-->P). Apparent permeability-surface area products (PS) were calculated from the rates of isotope appearance downstream in either the airspace or the perfusate. Equivalent pore analysis of data for P-->A solute flow demonstrated a small pore population with radius 0.6 nm occupying 85% of the total pore area and a large pore population with radius 3.8 nm occupying 15% of the total area. Similar analysis of A-->P solute flux demonstrated a small pore population of 0.6 nm occupying 86% of the total pore area and a large pore population with radius 2.9 nm occupying 14% of total pore area. The ratio (R) of PSP-->A divided by PSA-->P was 0.8 for the nonionic hydrophilic solutes, while R for sodium was 0.5. In the presence of amiloride and ouabain, R for sucrose was unchanged while R for sodium increased to 0.8 due to a fall in PSA-->P. The difference between R for sodium and R for the passively transported solutes, and the reduction in this difference in the presence of sodium transport inhibitors, are consistent with active sodium reabsorption by the intact alveolar epithelium. Differences in measured unidirectional passive solute fluxes probably result from unequal effective surface areas for diffusion from vascular space to airspace and vice versa in the anatomically complex mammalian lung. PMID- 8469855 TI - Angiotensin II stimulates respiration in awake dogs and antagonizes baroreceptor inhibition. AB - The effects of intravenous infusions of physiologic doses of angiotensin II (AII) on expired ventilation (VE) and acid-base balance were determined in awake dogs. A control infusion of saline was followed by AII infusion, initially with mean arterial pressure (MAP) raised 15%, and then with MAP at control levels by concurrent infusion of sodium nitroprusside (SNP). To control for SNP, the protocol was repeated using arginine vasopressin (AVP). Ventilatory responses to CO2 (VRC) were measured at the end of these protocols and separately with MAP elevated during infusion of AII. With AVP, increased MAP inhibited VE, heart rate (HR) and metabolism. However, with MAP elevated during AII infusion, stimulation by AII opposed baroreceptor reflexes and these variables, as well as plasma AVP, did not change. When MAP was lowered to control during AII infusion all variables increased. With AII, PaCO2 followed VE changes, decreasing 3 Torr with MAP at control levels; however, [H+] remained constant due to a decrease in arterial strong ion difference. The stimulatory effects of AII were not due to SNP; SNP did not stimulate VE during AVP infusion. The slope of the VRC was unaltered by AII infusion or MAP; however, AVP reduced the VRC slope. Physiological increases in AII stimulate VE and other systems at normal MAP and maintain several regulatory systems at control levels during baroreceptor inhibition. PMID- 8469856 TI - [Human cytogenetics is born in Liege 80 years ago (de Winiwarter, 1912)]. PMID- 8469857 TI - [Pseudo-asthma. Everything which wheezes is not asthma]. PMID- 8469858 TI - [Tuberculosis treatment in 1992]. PMID- 8469859 TI - [Current therapeutic methods in orthodontics]. PMID- 8469860 TI - [Blood preservation in surgery]. PMID- 8469861 TI - [Current aspects of locomotor pathology: benign tumors manifested in sports practice]. PMID- 8469862 TI - [Palmoplantar punctate keratosis]. PMID- 8469863 TI - [Malignant non-Hodgkins lymphoma with primary ovarian location. Observations apropos of a case]. AB - The authors report a case of primary ovarian non Hodgkin malignant lymphoma in a 41-year-old multiparous woman. An ovarian tumor was diagnosed in a context of hypogastric distention and discomfort. A total hysterectomy was performed with bilateral uterine appendectomy. The intra-abdominal organs were not affected and there were no internal adenopathies. The pathology examination concluded that this was a highly malignant, non-Hodgkin lymphoma. The findings of the extension assessment were negative. Five cycles of drastic chemotherapy combining bleomycin, adriamycin, cyclophosphamide, vincristine, methotrexate, iphosphamide, cisplatyl, VP-16 and ara-C have been administered and will be followed by abdominal radiotherapy. The patient is considered to be in a state of complete remission with a follow-up period of four years. PMID- 8469864 TI - [How can compliance be improved in hormone replacement therapy during menopause?]. AB - The main vital risks of the menopause and ageing are related to osteoporosis, cardiovascular accidents and cancer. Hormone therapy is effective against the first of these, but its efficacy against the second is difficult to measure in view of the number of factors involved and is even less clear against the third. Without any doubt it does improve all aspects of quality of life, so that it is rather surprising that only a minority of women receive treatment and that compliance with treatment is irregular, which is attributable to a variety of causes. Treatment protocols for the general situation and for specific cases are proposed. PMID- 8469865 TI - [Does a preventive treatment of pregnancy toxemia exist: the role of aspirin]. AB - After studying the risk factors of eclamptic toxemia, the author describes the various methods of prevention proposed. A salt-free diet has no effect. Increased intake of zinc or magnesium has no impact. Calcium (600 to 2,000 mg/d) may reduce the incidence of toxemia among teenagers from 27.9% to 4%. Low dose aspirin appears to be equally effective. Cod liver oil is currently being tested. PMID- 8469866 TI - [Ultrasound and twin pregnancy. The effect of placentation on fetal biometric growth and quantitative abnormalities of the amniotic fluid]. AB - Neonatal retarded growth and hypotrophy are more frequent in monochorial, biamniotic twin pregnancies than in bichorial ones. The authors consider the various pathogeneses which have been suggested to account for this phenomenon. PMID- 8469867 TI - [The fundamental basis and obstetrical applications of mifepristone or RU-486 (voluntary interrupted pregnancies excluded)]. AB - RU 486 is an anti-progesterone steroid used in obstetrics to achieve maturation of the cervix before an endouterine procedure in late abortions during the first 3 months, in therapeutic pregnancy termination during months 3-6 or 6-9 and in expelling fetuses which have died in utero. RU 486 has also been proposed for use in inducing or facilitating labor at term. PMID- 8469868 TI - [Management provided for a pelvic unilocular fluid image discovered in in a post menopausal female]. AB - After defining the procedures and limitations of ultrasound-guided puncture in woman of a sexually active age, the author considers the situation of menopausal women who, despite the commonly held opinion, can develop functional cysts. It is true, on the other hand, that they are exposed to a greater risk of cancer. However, in these women, cancer usually takes the form of peritoneal carcinosis and not that of a "cancerous cyst". In the post-menopausal woman, there is no need to envisage a modification of the response in a situation involving an ovarian cyst, particularly since the discriminating power of paraclinical tests is the same, if not greater (ultrasound, serum 125Ca assay), but particular vigilance is necessary in interpreting the symptoms and in managing follow-up if ultrasound guided puncture is the only procedure performed. If it is decided to operate, bilateral appendicectomy must be performed (together with verification of the uterine cavity). PMID- 8469869 TI - [The benefits and risks of laparoscopic surgery]. AB - The advantages of laparoscopic surgery in comparison to those of conventional surgery are mainly due to the very low rates of postoperative infections and adhesions and due to the aesthetic nature of this type of surgery. Endoscopy enables a thorough search of lesions which can then be treated in a more conservative manner. The short hospital stay and rapid postoperative recovery are two key advantages of endoscopic surgery. Complications at endoscopic surgery mainly occur if the safety measures are not strictly followed, due to improper choice and use of instruments (eg. old instruments), an antecedent laparotomy and also depend upon the type of surgery performed. It should be noted that the introduction of the trocar is not a simple affair, that non-recognition of complications is not infrequent and that the incidence of complications is directly proportional to the experience of the operator. PMID- 8469870 TI - [The value of zona drilling and sub-pellucida microinjections in severe asthenospermia in fertilization in vitro]. PMID- 8469871 TI - [Early determination of the fetal sex using ultrasonic measurements of the crown rump length]. PMID- 8469872 TI - [Detection of HBs antigens in pregnancy: a prospective study in Brittany in 1991]. PMID- 8469873 TI - [The value of fetal cerebro-placental velocimetry in the monitoring of twin pregnancies. Apropos of 72 consecutive cases]. PMID- 8469874 TI - [The exigency of rigorous control of publications and the validity of diplomas involving a specialty with high-risk medico-legal liability]. PMID- 8469875 TI - [Evaluation and performance of the follow-up in treated cancer of the breast]. AB - Follow-up of breast cancer is not always the same. On the basis of a retrospective study on 92 patients who presented with a progressive disease, the authors assess the effectiveness of complementary examinations and propose a follow-up protocol: clinical, laboratory tests, consisting of ESR, gamma GT, alkaline phosphatases, CA 15.3 every six months (or even every 4 months for CA 15.3) and radiological follow-up consisting of mammography and chest X-ray every year. Other examinations may also be prescribed if any change is detected by any of the tests listed above. The authors consider that this approach constitutes a balance between the minimalist and maximalist attitudes, and one which corresponds to the physician's duty to his patient. PMID- 8469876 TI - [The primary care midwife. An experience of integration]. PMID- 8469877 TI - [The laser in tracheobronchial pathology]. PMID- 8469878 TI - [Immobility in the elderly patient]. PMID- 8469879 TI - [The child and play]. PMID- 8469881 TI - [Energy and reflexology as holistic treatment]. PMID- 8469880 TI - [The fiber bronchoscope]. PMID- 8469882 TI - [The European Year of the Elderly and of Solidarity between Generations]. PMID- 8469883 TI - Lack of nurse practitioner program hurts Idaho nurses. PMID- 8469884 TI - A computerized state board exam for 1994. PMID- 8469885 TI - Stopping the Medicare tango. PMID- 8469886 TI - Nursing's agenda--in Bovill. Interview by Heidi Crouch. PMID- 8469887 TI - Idaho Falls Recovery Center--the dream becomes reality. PMID- 8469888 TI - [Injury of the spine. Diagnosis, development, prognosis]. PMID- 8469889 TI - [Recent injuries of the ankle. Diagnostic orientation]. PMID- 8469890 TI - [Urticaria and Quincke's edema. Etiology, diagnosis, treatment]. PMID- 8469891 TI - [Iatrogenic agranulocytosis. Etiology, diagnosis, treatment]. PMID- 8469892 TI - [Interleukins and TNF in septic shock]. AB - Tumor necrosis factor alpha (TNF alpha) and interleukins (IL) are the principal cytokines involved in the clinical and biological manifestations of septic shock. Their secretion are triggered mainly by endotoxin, but products of Gram positive cocci as well as of virus or of parasites are equally effective. Cytokines represent a normal protective defense against infection, but an excessive production have toxic effects. In experimental models of endotoxinemia, TNF alpha is the first cytokine produced, then IL-1 and IL-6. Other inflammatory mediators are secreted later. Thus it seems logical to try to modulate cytokine production or actions. However, several questions remains since experimental data are sometimes not applicable too human diseases, cytokines are organised in a network with several interaction. It is too early to propose routine anti-cytokines drugs in septic shock. PMID- 8469893 TI - [Other mediators of inflammation and sepsis]. AB - During sepsis, the systemic inflammatory response is characterized by the release of numerous mediators supporting and dispersing inflammation. In Gram negative sepsis, the endotoxins play a starting role, while in other sepsis, the triggering mediators or mechanisms are unknown but lead to a similar inflammatory reaction. Coagulation and complement cascades are activated, with the release of chemoattractive substances, mediators and proteases and the activation of phagocytic cells. Macrophages/monocytes and polymorphonuclear leucocytes produce then active oxygen species and cytokines; they degranulate (releasing active enzymes such as myeloperoxidase), they express an increasing number of membrane receptors able to interact with endothelial cells and release a supplementary lot of inflammatory mediators (prostanoids, platelet activating factor, leukotrienes ... ). Platelets, also activated, produce the same mediators (TXA2, PAF ...) or specific ones such as serotonine, platelet factor 4, growth factors. Last, but not least, the endothelial cells are stimulated, directly (by endotoxins) or undirectly (by cytokines, C5a, PAF ...). These cells play then a main role by their own phagocytic activity, by alteration of their antithrombotic and fibrinolytic potential, by their secretion of inflammatory mediators and by an increased expression of receptors of adhesivity for the activated phagocytes or platelets, what leads to endothelium injury with membrane permeability alterations. These cascades of activation, these extensions of the inflammatory reaction by the mediators and by the phagocytes and platelets can explain the frequency of multiple organ failure during sepsis as well as the difficulty of an adequate pharmacological therapy. PMID- 8469894 TI - [Septic shock and regional circulations]. AB - Owing to the scarcity of clinical studies on this subject, one must turn to experimental data, with reservations concerning their extrapolation to human beings. Septic shock, a distributive shock, results from a homogeneous decline of vascular tone and therefore regional blood flows. Direct vasodilators, such as nitric oxide and prostaglandins, and indirect vasodilators, such as cytokines, produce vasodilation with hypocontractility. During hyperkinetic shock in animals, dilatation of the mesenteric and coronary arteries is observed, with reduction of pancreatic and skin muscle flows. Two clinical studies have confirmed this coronary vasodilatation without increase in myocardial oxygen consumption. In the liver the hepatic artery buffer response is altered, the portal flow rate is reduced without changes in portal vein pressure, and the hepatic vein saturation is less than that of the pulmonary artery, thus testifying to an increase of oxygen extraction, mainly in the liver. The hepatic flow rate is also influenced by the liver glucose content. The mesenteric and pancreatic circulations are particularly threatened, their flow rate being reduced by 50% due to vasoconstriction. In the kidney the flow rate is biphasic: high first, then low. Treating hypovolaemia does not prevent the renal function from being altered, even when the flow rate is maintained. Blood flow is reduced in the respiratory muscles, despite an increase in work and oxygen consumption. Finally, treatment with vasopressors does not seem to correct the disorders observed in cardiac output distribution and has little increasing effect on arterial blood pressure. PMID- 8469895 TI - [Myocardial dysfunctions in septic shock]. AB - Acute myocardial dysfunction is part of the initial presentation of septic shock. This sudden and more or less intense dysfunction is potentially reversible. It consists of a disturbance of the systolic function in both ventricles, manifested by an ejection fraction degression which persists after correction of a possible hypovolaemia, associated with a disturbance of the diastolic function which restricts ventricular filling. These cardiac disorders interfere with adaptation to the sepsis and are clinically expressed by tachycardia. PMID- 8469896 TI - [Clinical and etiological diagnosis of septic states]. AB - The sepsis concept implies a clinical suspicion of infection and a diagnosis of host's response to this infection. In increasing order of severity are simple sepsis, severe sepsis and septic shock. The semeiology of sepsis consists of systemic signs and elements of information on various visceral dysfunctions. The aetiological investigation is based on the patient's diathesis, on whether the infection is hospital- or community-acquired, on the severity of the sepsis and on simple clinical and paraclinical data. Gram-positive infections are usually caused by pneumococci and staphylococci, and Gram-negative infections by meningococci and enterobacteriaceae. Hospital-acquired infections are remarkable for their frequency, their severity and the diagnostic problems they raise due to patients' colonization and multiple portals of entry. With the exception of some microbiological situations (parasites, fungi, viruses), the main problems raised by non-bacterial sepsis relate to occult sepsis and systemic inflammatory responses to some acute pathologies, such as burns, pancreatitis or multiple injuries. To conclude, redefining the nosology of severe infections to include the fundamental concept of host's response should result in a better evaluation of the infection, its consequences and the treatment of both. PMID- 8469897 TI - [Developmental modalities of septic states. Multiple organ failure syndrome]. AB - Sepsis syndrome occurs when an acute infection results in an host generalized inflammatory response including cytokines production. Death is a frequent and unpredictable sequel of this pathological condition. It may be due either to uncontrolled circulatory failure, or to multiple organ failure. With the advent of nitric oxide in the arena of the most potent vasodilatator agents, we now better understand the mechanisms of low vascular resistance during hyperkinetic septic shock. However a closer understanding of the mechanisms of multiple organ failure is actually required to improve survival rates during severe human sepsis. PMID- 8469898 TI - [Symptomatic treatment of septic shock]. AB - Septic shock is characterized by an important vasoplegia associated with an oxygen extraction abnormality probably linked to the presence of a biochemical alteration at the microcirculatory level. Hemodynamic intervention requires aggressive fluid resuscitation complemented if necessary by the use of sympathomimetic amines (dopamine and often epinephrine, norepinephrine). Dobutamine is indicated when left ventricular dysfunction was obviously demonstrated. Swan Ganz catheter is required when hemodynamic intervention -ie fluid resuscitation and dopamine-remains unefficacious. However the earlier indication of Swan Ganz catheter use might be justified by the necessity of a precise preload evaluation and the possibility of the determination of the best oxygen transport. PMID- 8469899 TI - [Antibiotic treatment of septic states]. AB - The antibiotic therapy in septic syndrome is most often empiric. Decisions and antibiotic choices should result from a careful analysis of past history and setting (hospital-acquired infections vs community acquired infections), risk factors specific to the host, and characteristics of the suspected infections focus: direct examination of body fluid specimens should be obtained rapidly to guide the empiric choice. The choice of antibiotics should conform to usual guidelines, with the aim of a rapid bactericidal effect in blood, while attempting to avoid risks of toxicity. Changes in pharmacokinetics of drugs are usual in this context, and frequent dosing is necessary. While effective antibiotic therapy is a recognized prognostic parameter, antibiotics are only one part of therapy, besides supportive therapy of failing organs, and effective drainage or surgery of the infected focus, when feasible. PMID- 8469900 TI - [Therapeutic perspectives of severe infectious states]. AB - Mortality from sepsis is still unacceptably high which justifies a new therapeutic approach complementary of antibiotics and symptomatic treatment. Recent advances in the understanding of sepsis and septic shock opened new fields of therapeutic intervention. Nevertheless, there are so many potential targets that is hard to make a choice for evaluation of these new agents: anti-endotoxin (monoclonal antibodies, lipid A analogs, BPI), anticytokines (monoclonal antibodies, soluble receptors, IL-1 receptor antagonist), anti-inflammatory agents (non-steroidal anti-inflammatory agents, anti-PAF, reactive oxygen radicals scavengers...), extracorporeal removal of toxic molecules, inhibition of the adhesion of polymorphonuclear leucocytes on endothelial surface, optimisation of general and regional circulation. The use of these new and often costly drugs must rely on multicenter randomized clinical trials since extrapolation to the human of experimental data gathered in animal studies are hazardous. PMID- 8469901 TI - [Mammographic screening. A key examination for the early diagnosis of breast cancer]. PMID- 8469902 TI - [Surgical treatment of spinal metastasis. Controlled therapeutic management of pain and neurologic compression]. PMID- 8469903 TI - [Branhamella catarrhalis. Rediscovery of a pathogenic bacterium]. PMID- 8469904 TI - [A few facts acquired apropos of the treatment of myocardial infarction]. PMID- 8469905 TI - [Suicidal ideas or behaviors. Diagnostic orientation]. PMID- 8469906 TI - [Convulsive seizure. Diagnostic orientation and emergency treatment with posology]. PMID- 8469907 TI - [Vomiting in infants. Diagnostic orientation]. PMID- 8469908 TI - [Non-traumatic coma. Diagnostic orientation]. PMID- 8469909 TI - Contributions to the treatment of primary liver cancer. 4'-epidoxorubicin and cisplatin studied in hepatocarcinoma cell cultures and in partially hepatectomized rats. PMID- 8469910 TI - Inhibitors of the arachidonic acid metabolism attenuate the thyroliberin (TRH) stimulated prolactin production without modifying the production of inositolphosphates in GH4C1 pituitary cells. AB - Some arachidonic acid metabolites might be among the intracellular signalling substances that regulate hormone release. We report that the phospholipase A2 and diacylglycerol lipase inhibitor quinacrine (1-10 mumol l-1) inhibited the thyroliberin stimulated prolactin (rPRL) production in a dose-dependent way in a rat pituitary tumour cell line (GH4Cl cells). The lipoxygenase inhibitor nafazatrom (5-50 mumol-1) also dose-dependently inhibited the thyroliberin stimulated rPRL production, while the cyclo-oxygenase inhibitor indomethacin had no such effect on rPRL production. The inhibitors of the arachidonic acid metabolism (quinacrine, ETYA and nafazatrom) had no effect on the accumulation of inositolpolyphosphates indicating that the arachidonic acid metabolites are not involved in the regulation of the phospholipase C activity. PMID- 8469911 TI - Glycation and oxidation of human low density lipoproteins reduces heparin binding and modifies charge. AB - The effects of glycation and oxidation of human low density lipoproteins (LDL) on heparin binding were studied and compared with modifications in the charge of the particles. Glycation of LDL at a molar ratio of 4 mol glucose mol-1 apoB, decreases affinity for heparin, as shown by heparin-agarose affinity chromatography since salt molarity needed for elution decreases from 550 mmol l-1 for control LDL (c-LDL) to 350 mmol l-1 for glycated LDL (glc-LDL). Oxidized LDL (oxi-LDL) shows marked heterogeneity, most of the fractions having decreased affinity. Heparin-agarose affinity chromatography of LDL preparations shows the presence of a small (5-7%), low-affinity fraction in euglycaemic human plasma LDL (c-LDL). Its elution volume coincides with both glc-LDL and a fraction of oxi LDL, suggesting it may contain glycated and oxidized molecules present in plasma. DEAE-Trisacryl anion exchange chromatography elution profiles of c-LDL preparations shows the presence of a more electronegative fraction accounting for about 10% of total protein. This fraction elutes with 260 mmol l-1 NaCl instead of 130 mmol l-1 for the main fraction, it roughly coincides with elution volumes of main peaks of glc-LDL and oxi-LDL. Results indicate that glycated particles may be present in this fraction. Our data demonstrate then that glycation, and to a lesser degree, oxidation of LDL reduce affinity to heparin. From an analytical approach, modified LDL can be separated from the bulk of native LDL both by DEAE and heparin-agarose chromatographies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469912 TI - An enzyme-linked immunosorbent assay for plasma-lactoferrin. Concentrations in 362 healthy, adult blood donors. AB - Very different concentrations of plasma-lactoferrin in healthy adults have been reported in the literature. We compared three commercially available lactoferrins and lactoferrin purified in our laboratory as calibrators in an ELISA. No statistical differences among these preparations of lactoferrin were detected. The concentration of purified lactoferrin was measured by dry weight, and efforts were made in order to minimize loss of purified lactoferrin by adhesion to tubes etc. and thus, secure accuracy of the method. Dilutions were made in PBS 0.01 mol l-1 with NaCl 0.436 mol l-1, (NH4)2SO4 0.5 mol l-1, BSA 5 gl-1 and normal rabbit IgG 10 mg l-1, which was shown to give parallel dilution curves of primary calibrator, secondary calibrator and plasma samples. No significant difference in the content of lactoferrin in neutrophils (median; range) among men (1.78; 0.83 4.48 micrograms 10(-6) neutrophils; n = 20) and women (2.12; 1.16-9.30 micrograms 10(-6) neutrophils; n = 14) was found. Lactoferrin was analysed in EDTA-plasma obtained from 135 female and 227 male blood donors. Median concentrations were 84.7 and 97.8 micrograms l-1 respectively, while 2.5% and 97.5% reference limits (with 90% confidence intervals) were estimated to 42.9 (38.7-47.4) micrograms l-1 and 166.9 (151.0-186.3) micrograms l-1 for women and 52.3 (49.1-55.6) micrograms l-1 and 189.9 (175.9-206.4) micrograms l-1 for men, respectively. PMID- 8469913 TI - An ELISA for elastase alpha 1-protease inhibitor complexes in human plasma and serum. AB - An ELISA for neutrophil elastase (ELA) in complex with alpha 1-protease inhibitor (PI) (alpha 1-antitrypsin) was developed in microtitre plates and compared to the ELISA kit from MERCK (2-h version). Recovery of ELA-PI was good in both assays. The detection limits were 4.4 micrograms l-1 and 7.7 micrograms l-1 of the in house and MERCK assay, respectively, while limits of quantitation were estimated to 7.7 micrograms l-1 (5.5-9.9 micrograms l-1) and 28.9 micrograms l-1 (14.6-44.3 micrograms l-1) for the two assays. Furthermore, as dilution curves of normal plasma were parallel with the calibration curve in the in-house assay over a wide range of dilutions, it is feasible to assay plasma in dilutions of only 1:6, resulting in a limit of quantitation of only 1.1 micrograms l-1. The total analytical coefficient of variation for samples measured in double determinations was 10.5%-12.5% in the in-house assay and 13.9%-14.6% in the MERCK assay. One hundred-and-eight plasma samples covering a wide range of ELA-PI concentrations were analysed in both assays. A proportional difference between the two methods was detected, the mean ratio (in-house/MERCK) with 95% confidence limits was 1.115 (1.070-1.160). The cause of the difference was probably due to difference calibration of the assays. Until this problem is solved, method specific reference intervals are needed. A reference interval for the in-house method based on plasma samples from 123 healthy adults; median age 36 years (range: 19 65 years) was estimated to 16.5-48.5 micrograms l-1. PMID- 8469914 TI - Left ventricular end-diastolic dimensions measured at the P wave and Q wave during a randomized, double-blind one-year follow-up study comparing the effect of atenolol vs. hydrochlorothiazide + amiloride on blood pressure in men with mild to moderate hypertension. AB - Echocardiographic measurement of left ventricular (LV) end-diastolic dimensions and mass (M) were made at baseline, at 3 and 12 months of a randomized trial comparing atenolol 50/100 mg od. and hydrochlorothiazide 25/50 mg+amiloride 5 mg od. (co-amiloride) in 100 men with mild to moderate hypertension. Data from 48 subjects controlled adequately on drug monotherapy and completing 12 months treatment are reported (31 randomized to atenolol and 17 to co-amiloride). Left ventricular mass was measured with the Penn convention at the R and P wave respectively. A significant reduction of LVM was noted after one year in both groups (p < 0.05) when measured at the R, but not at the P wave. Measurements according to American Society of Echocardiography (ASE method) at the Q wave revealed a significant reduction of LV wall thickness (p < 0.01) and an increase of LV internal diameter (p < 0.01) with atenolol. In the co-amiloride group non significant reductions of LV dimensions were observed. Principally similar changes were observed with measurements at the P wave (National Institute of Heart method) in both groups, but LV wall thickness was greater and LV internal diameter smaller than at the Q wave. With similar effect on LVM, the mechanisms in reducing LVM were different between the two drugs. Left ventricular dimensions differed when assessed with the two methods applied, stressing the need for careful standardization in relation to the cardiac cycle in serial echocardiographic measurements. PMID- 8469915 TI - Assessment of glycaemic control in non-insulin-dependent diabetes mellitus. AB - Blood glucose profiles, fasting blood glucose and glycated haemoglobin were followed prospectively for 6 weeks in 14 patients with non-insulin-dependent diabetes (NIDDM). Capillary blood glucose was sampled weekly on filter paper and analysed in the laboratory. Glycated haemoglobin was determined every other week with both cation-exchange chromatography (HbA1-IEC) and aminophenylboronic acid affinity chromatography (GHb-PBA). The mean for the blood glucose profiles was 11.2 +/- 3.5 mmol l-1 (+/- SD) and the mean for fasting blood glucose was 9.5 +/- 2.8 mmol l-1. For individual patients the differences between mean fasting blood glucose and mean blood glucose varied from -1.3 to 4.2 mmol l-1. There was a linear relationship between blood glucose and glycated haemoglobin which was steeper for GHb-PBA than for HbA1-IEC. The correlations with fasting blood glucose and mean blood glucose for HbA1-IEC were r = 0.85 and r = 0.92 and for GHb-PBA r = 0.87 and r = 0.96 respectively. Mean blood glucose was better correlated to glycated haemoglobin than fasting blood glucose (p < 0.05 for GHb PBA). PMID- 8469916 TI - Luminol enhanced Fc-receptor dependent chemiluminescence from peripheral PMN cells. A methodological study. AB - Maximal luminol enhanced chemiluminescence (CL) of PMN cells after Fc-gamma receptor stimulation is a way to study the cell activity in connection with phagocytic function. Optimal conditions for such a method were elaborated for practical clinical use. After blood sampling and gentle mixing the blood sample was allowed to stand at +20 degrees C for not more than 1 h. The PMN cells prepared at +20 degrees C were washed at +4 degrees C with a phosphate buffer containing human serum albumin. A gentle lysis of the red blood cells with NH4Cl solution reduced the number of red cells sufficiently not to interfere with the CL. Important factors for the precision of the method were reproducible amounts of bacteria and a reproducible mixing of the particles during the CL analysis. The method had a variation (CV) of 10-15% in healthy individuals. PMID- 8469917 TI - Coagulation factors and lipid composition of the blood in treated and untreated hypertensive patients. AB - The cardiovascular risk factors blood pressure, overweight, hyperlipidaemia and several coagulation parameters were studied in a group of 54 otherwise healthy patients with essential hypertension of moderate severity. Of the 54 hypertensive patients, 43 were treated with anti-hypertensive drugs and 11 were not. The patients included in this study who were treated with anti-hypertensive drugs were still hypertensive in spite of their treatment. Lipoprotein levels and coagulation parameters did not differ between the untreated and treated hypertensive patients. Substantial percentages of patients were found to have hypertriglyceridaemia (46%), elevated LDL-cholesterol (28%) and elevated lipoprotein(a) concentrations (43%). Coagulation factors F VIIIc, fibrin monomer and factor VII in males were significantly elevated in comparison with a healthy reference group. These data are compatible with a moderate activation of the coagulation system. Correlations were established between systolic blood pressure and serum cholesterol (r = 0.43, p = 0.003), LDL-cholesterol (r = 0.34, p = 0.02) and triglycerides (r = 0.35, p = 0.01); Quetelet-index with fibrinogen (r = 0.37, p = 0.02) and thrombin-antithrombin III (r = 0.30, p = 0.04); and triglycerides with F VIIc (r = 0.34, p = 0.03) and fibrin monomer (r = 0.29, p = 0.04) respectively. These data link hypertension and hyperlipidaemia with increased coagulation activity and may contribute to our understanding of why these two cardiovascular risk factors accelerate atherogenesis. PMID- 8469918 TI - Increased urinary loss of high density lipoproteins in albuminuric insulin dependent diabetic patients. AB - The pathophysiological mechanisms resulting in hyperlipidaemia in albuminuric insulin-dependent diabetic patients are largely unknown. Increased non-specific hepatic protein synthesis as a response to urinary protein loss, has been proposed. However in that case it is unexplained why the plasma concentration of the high density lipoprotein (HDL) subfraction, in contrast to all other lipoprotein subfractions, is normal or even reduced in albuminuric patients. We studied the urinary excretion of HDL-cholesterol in 26 insulin-dependent diabetic patients matched according to sex and age into three groups. I: normal urinary albumin excretion (< 30 mg 24 h-1; n = 8); II: incipient nephropathy (urinary albumin excretion in the range of 30-300 mg 24 h-1; n = 7); and III: clinical nephropathy (urinary albumin excretion > 300 mg 24 h-1; n = 11). Eight normal subjects served as controls. Lipoproteins in urine were separated by ultracentrifugation, and the daily urinary loss of HDL-cholesterol was 1.30 mumol (0.83-2.21) (median and range) in controls, 1.27 mumol (0.56-2.59) in group I, 1.39 mumol (0.55-1.97) in group II and 4.02 mumol (1.33-42.12) in group III (p < 0.01). More than 95% of cholesterol in urine was found in the HDL-fraction. The plasma concentrations of total cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol and triglyceride were 21-94% higher in patients with clinical nephropathy compared with normal controls and group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8469919 TI - Continuous blood gas monitoring in haemodialysis using an electrode inserted in the extracorporeal dialysis circulation. AB - The aim of this study was to evaluate the usefulness of continuous gas monitoring during haemodialysis using an oxygen- and carbon dioxide-sensitive electrode inserted in the 'arterial' line from the arteriovenous fistula. We investigated 15 patients with chronic renal failure, treated with regular bicarbonate haemodialysis. The PO2 and PCO2 were measured by the new method and compared to conventional blood gas analysis of the 'arterial' blood from the dialysis circulation. We found the in situ gas sensors were stable and there was no systematic difference between gas tensions measured by in situ and conventional blood gas measurements. The standard deviations of the difference between paired measurements for PO2 and PCO2 were 1.3 and 0.4 kPa, respectively. Therefore, the method can be used to detect major changes in blood gas tensions during haemodialysis. PMID- 8469920 TI - Release of atrial natriuretic factor. AB - The cardiac atria synthesize and store a hormone termed atrial natriuretic factor (ANF). ANF is released into the systemic circulation, and the circulating 28 amino acid peptide can be measured by radioimmunoassay. The hormone participates in body fluid homeostasis through its effect on renal sodium excretion and by inducing a shift of circulating fluid to the interstitial space. Release of ANF is mainly regulated by mechanical changes in the left and right atrial wall. It has been demonstrated that ANF release is related to changes in atrial wall tension occurring during each atrial cycle, and therefore, release of ANF will increase with increasing heart rate. Not only the increase in wall tension during passive atrial distension (v wave), but also the increase in tension during atrial systole (a wave) are determinants of ANF release. The mechanochemical transducer is most likely located in the atrial myocytes, but its nature is unknown. There is no evidence to suggest that efferent cardiac nerves are essential in the regulation of ANF release. Humoral factors have been suggested as regulators of ANF release, particularly catecholamines and angiotensin II. A receptor-mediated direct stimulatory effect of alpha-adrenergic stimulation and an inhibitory effect of beta-adrenergic stimulation have been demonstrated, but these direct effects are small compared to the effect of changes in atrial wall tension. Circulating catecholamines and angiotensin II stimulate ANF release mainly through their haemodynamic effects. PMID- 8469921 TI - The Nobel Lectures in Immunology. Lecture for the Nobel Prize for Physiology or Medicine, 1984. From the structure of antibodies to the diversification of the immune response. PMID- 8469922 TI - On the interaction between protein L and immunoglobulins of various mammalian species. AB - Protein L, a cell wall molecule of certain strains of the anaerobic bacterial species Peptostreptococcus magnus, shows high affinity for human immunoglobulin (Ig) light chains. In the present study protein L was tested against a panel of human myeloma proteins of the IgG, IgM, IgA and IgE classes, and strong binding was seen with antibodies carrying kappa light chains. A high degree of specificity for Ig was demonstrated in binding experiments with human plasma proteins. Apart from human Ig, strong protein L-binding activity was also detected in the serum of 12 out of 23 tested additional mammalian species, including other primates and rodents. Subsequent analysis with purified Ig samples demonstrated the binding of protein L to Ig of important laboratory animal species such as the mouse, the rat and the rabbit. The affinity constants for the interactions between protein L and polyclonal IgG of these species were 2.6 x 10(9), 3.9 x 10(8) and 7.4 x 10(7), respectively. In non-human species, the binding of protein L was also found to be mediated through Ig light chains, and the results demonstrate the potential value of protein L as an immunochemical tool. PMID- 8469923 TI - Anti-interleukin-2 receptor monoclonal antibody therapy supports a role for Th1 like cells in HgCl2-induced autoimmunity in rats. AB - Brown-Norway (BN) rats injected with HgCl2 develop an autoimmune disease characterized by a T-dependent polyclonal B-cell activation. Increase in major histocompatibility complex class II molecule expression on B cells concomitant with enhancement of serum IgE concentration supports the involvement of the T helper 2 (Th2)-like subset in the induction of the disease. The mercury disease is autoregulated and does not develop in Lewis (LEW) rats. Considering the reciprocal regulation, well defined in mice, between the Th1 and Th2 subsets, we addressed the role of the Th1-like subset in this disease. Brown-Norway and LEW rats injected with HgCl2 were treated with NDS61, a mouse anti-rat-IL-2R MoAb that blocks mainly Th1 cells. Data reported herein show that: (1) HgCl2 treatment does not modify either the percentage of IL-2R+ cells or IL-2R expression in both BN and LEW rats; (2) treatment of BN rats with NDS61 MoAb does not modify the induction phase of the mercury disease but delays in part the regulation phase; (3) such a treatment leads to some immune abnormalities in LEW rats; (4) HgCl2 markedly potentiates the anti-mouse Ig antibody response in BN rats which probably limits the effect of this treatment. This study supports a role for the Th1-like subset in HgCl2-induced autoimmunity in the rat. PMID- 8469924 TI - Cytotoxic T-cell clones isolated from ovarian tumour infiltrating lymphocytes recognize common determinants on non-ovarian tumour clones. AB - CTL-TIL lines have been developed from tumour infiltrating lymphocytes (TIL) from the ascites of patients with ovarian carcinoma, and used to investigate whether common tumour antigens are expressed on allogeneic ovarian tumours epithelial tumour lines derived from colon and pancreatic carcinoma. Three CTL lines expressed preferential cytolytic activity against autologous tumour cells and against certain allogeneic ovarian tumour cells that shared HLA-A2 molecules. Analysis of the target specificity of these CTL lines indicated that they also lysed human colon and pancreatic tumour lines sharing HLA-A2. CTL-TIL clones isolated from these lines were found to lyse HLA-A2+ ovarian, colon and pancreatic tumours, and to recognize clonally distributed common epitopes on pancreas and colon tumour clones. These results indicate that shared tumour antigens can be found among tumours of common epithelial cell origin. These results indicate a novel class of T-cell-definable tumour antigens recognized by tumour-reactive CTL on human tumours and may be significant for understanding of cellular immunity in ovarian cancer, identification of CTL-defined tumour antigens and future adoptive specific immunotherapeutic approaches in ovarian cancer. PMID- 8469925 TI - Partial biochemical characterization and purification of IgG2b inducing factor as a new cytokine from synovial fluid of patients with rheumatoid arthritis. AB - Rheumatoid arthritis synovial fluid (RA-SF) contains a novel biological activity, which selectively induces IgG2b antibody production in lipopolysaccharide (LPS) activated mouse spleen cells in vitro and in vivo. Our previous studies have shown that this activity is not functionally identical to other well-known cytokines and interleukins. In this study we demonstrate the partial purification and biochemical characterization of the IgG2b inducing activity in RA-SF. Biochemical characterization revealed that the IgG2b inducing activity in RA-SF has the following properties: it is a protein, sensitive to pH > 11 and < 4, which is precipitated by 50% of saturated ammonium sulphate and has a molecular weight of 50-70 kDa; it binds to Cibacron-blue and heparin and its activity is not mediated by immunoglobulins or immune complexes, which are present in RA-SF. Biochemical characteristics of the IgG2b inducing activity also differ from other cytokines and interleukins. The term IgG2b inducing factor is proposed for this novel activity. PMID- 8469926 TI - Differences in the rate of intracellular killing of catalase-negative and catalase-positive Listeria monocytogenes by normal and interferon-gamma-activated macrophages. AB - Intracellular killing of catalase-positive bacteria by murine resident macrophages requires the presence of extracellular serum, whereas killing of catalase-negative bacteria can occur in the absence of serum. To find out whether the intracellular killing of bacteria by rIFN-gamma-activated macrophages also requires serum stimulation, we investigated the handling of ingested catalase negative and -positive Listeria monocytogenes by peritoneal macrophages of normal Swiss mice and mice injected i.p. with 1 x 10(4) U rIFN-gamma 18 h earlier. In the absence of extracellular serum, rIFN-gamma-activated macrophages killed ingested catalase-negative Listeria more efficiently (P < 0.01) than normal resident macrophages. Maximal killing of catalase-negative bacteria by rIFN-gamma activated macrophages required an extracellular serum concentration of only 1.0 to 2.5% compared with the 10% needed by normal macrophages. No differences were observed in the rates of intracellular killing of catalase-positive Listeria by rIFN-gamma-activated and normal resident macrophages: both populations of macrophages required 10% extracellular serum for maximal killing of these bacteria, and killing was minimal in the absence of serum. The rIFN-gamma activated macrophages displayed enhanced O2-consumption after stimulation with phorbol myristate acetate and heat-killed Listeria compared with macrophages from normal mice. These findings indicate that, under suboptimal stimulation by extracellular serum, rIFN-gamma enhances the intracellular killing of catalase negative Listeria which lack endogenous catalase acting as a scavenger of reactive oxygen intermediates. The mechanism underlying the enhancement is probably the amplification of the respiratory burst by IFN-gamma. PMID- 8469927 TI - The primary structure of rabbit serum amyloid A protein isolated from acute phase serum. AB - Serum amyloid A (SAA) protein, a sensitive acute phase protein and the precursor of protein AA in secondary amyloid, was purified from pooled acute phase rabbit serum using two different methods: isolation of protein SAA directly by octyl Sepharose chromatography of total serum, and dissociation and isolation of apoSAA from acute phase high density lipoprotein (HDL). The protein SAA fraction obtained was further purified using gel filtration and ion exchange chromatography. Rabbit protein SAA has 104 amino acid residues, like human SAA, and has a partially blocked N terminus. The highly conserved region from position 33 to position 63 found in SAA from all species studied was confirmed also in rabbit SAA. No microheterogeneities were observed. The amino acid sequence showed extensive N-terminal homology with the rabbit amyloid A protein, except for the microheterogeneity in position 12 in protein AA. It also showed identical amino acid sequence with that deduced from the rabbit cDNA clone pSAA 55. Complete homologies were found with clone SAA 2, except for positions 22 and 78, clone SA8 1, except for positions 22 and 79 and clone SA7-3, except for position 22. This pSAA 55/SA7-3/SA8-1/SAA2-like protein was the only SAA isotype found both in total serum and in the HDL fraction. Isotypes corresponding to other SAA-like genes could not be found in this pool of acute phase rabbit sera. PMID- 8469928 TI - Cholera toxin enhances alloantigen presentation by cultured intestinal epithelial cells. AB - In the present study we show that cholera toxin (CT) strongly potentiates antigen presentation by intestinal epithelial cells, probably by enhancing co stimulation. This was demonstrated in an allogeneic system using cells from the IEC-17 rat epithelial cell line as antigen presenting cells (APC). These cells were induced by optimal concentrations of IFN-gamma to express good amounts of Ia antigen and cultured for 24-48 h in the presence or absence of CT. Thereafter the cells were thoroughly washed and added to cultures containing MHC-incompatible spleen cells as responder cells. Epithelial cells exposed to CT demonstrated greatly enhanced ability to trigger allogen-specific T-cell proliferation as compared with IEC-17 cells treated with IFN-gamma alone. The mechanism for the enhanced APC function was investigated by analysing CT-treated IEC-17 cells for increased class II MHC antigen expression or enhanced production of cytokines with known co-stimulatory function. We found no significant increase in class II MHC antigen expression. By contrast, CT strongly promoted, in a dose-dependent fashion, the production of both IL-1 and IL-6 cytokines by IEC-17 cells as compared with untreated epithelial cells. This effect of CT was specific and not due to contaminating endotoxin because excess amounts of soluble toxin receptor, ganglioside GM1, added to the IEC-17 cultures completely abrogated the cytokine response to CT. These results together with our previous findings of enhanced antigen presentation by macrophages stimulated by CT suggest that the potent adjuvant function of CT for induction of mucosal immune responses might be attributed to an enhanced co-stimulating ability of several putative APC in the mucosal immune system: macrophages, B cells and epithelial cells. PMID- 8469929 TI - Modification of lymphocyte and monocyte functional activity by polymorphonuclear neutrophils in HIV infection. AB - The aim of this study was to determine whether polymorphonuclear neutrophils (PMN) can modify the immune response in HIV cases. Supernatants of PMN (PMNS) from 33 HIV-infected patients (16 with lymphoadenopathy syndrome, 17 with AIDS related complex) were tested for their influence on the functional activity of lymphocytes and monocytes from 6 healthy donors. PMNS from another 6 healthy donors comprised a control group. It was found that PMNS from HIV-infected patients, but not from healthy donors, induced suppression of lymphocyte proliferative response and down-regulation of CD8 receptor expression on lymphocytes. Decrease of NK-cell cytotoxicity in the presence of PMNS from HIV infected patients was the same as that from healthy donors. PMNS did not influence the production of anti-HIV antibody by lymphocytes from HIV-infected patients, as well as non-specific IgG by lymphocytes from healthy donors. PMNS effect on functional activity of lymphocytes was blocked completely after treatment of PMN by catalase and superoxide dismutase. At the same time PMNS from HIV-infected patients but not from healthy donors induced increased production of TNF-alpha by monocytes and up-regulation of monocyte phagocytosis. These effects were independent of catalase and superoxide dismutase and were not abrogated by antibody against IL-1, IL-8, TNF-alpha, IFN-gamma or IFN-alpha. PMID- 8469930 TI - A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease. AB - The mammalian C-type serum lectin, mannan-binding protein (MBP), may induce C1q- and antibody-independent activation of the classical pathway of complement. Accordingly, MBP is considered as a member of the complement system. Complement deficiencies have been found with increased frequency in patients with meningococcal disease. Therefore, we investigated the MBP levels in patients with meningococcal disease. Ninety-nine Norwegian individuals (age 12-21 years) who survived severe systemic disease caused by serogroup B or C meningococci were investigated. No significant differences were observed in the MBP concentration between patients with serogroup B (n = 76) or C (n = 25) disease and healthy blood donor controls (n = 40) (P > 0.05). The frequency of patients with low levels of MBP (< 100 micrograms/l) was 10.1%. This was not different from controls (12.5%). Thus, low MBP concentrations do not appear to predispose to serogroup B or C meningococcal disease. PMID- 8469931 TI - Identification of a novel 27-kDa protein from Mycobacterium tuberculosis culture fluid by a monoclonal antibody specific for the Mycobacterium tuberculosis complex. AB - Mycobacterium tuberculosis antigens inducing species-specific immune responses are likely to be particularly important for serodiagnosis or for skin testing of tuberculosis. In the present study, we describe the characterization of two novel monoclonal antibodies (MoAbs) A3h4 (IgG2a) and B5g1 (IgM) that are directed to M. tuberculosis 27-kDa and 25-kDa proteins respectively. Specificity analysis by immunoblotting using 20 different species of mycobacterial sonicates revealed that MoAb A3h4 was specific for M. tuberculosis complex alone while MoAb B5g1 showed a limited cross-reactivity. Direct comparison with previously characterized MoAbs revealed that these MoAbs A3h4 and B5g1 defined new antigenic determinants of M. tuberculosis. By using M. tuberculosis complex-specific MoAb A3h4 we have identified a distinct 27-kDa protein in the M. tuberculosis H37Rv culture fluid. Since this MoAb did not bind to the previously characterized MPT44, MPT59, MPT45, MPT51 and MPT64 proteins as well as the 23-kDa superoxide dismutase (SOD) protein of M. tuberculosis, we conclude that MoAb A3h4 recognizes a novel protein in the M. tuberculosis H37Rv culture fluid. Studies of the subcellular distribution of these MoAb-reactive proteins indicate that the MoAb A3h4-reactive 27-kDa protein is present not only in the culture fluid but also in the cytosol and the cell wall of M. tuberculosis. By contrast, B5g1-reactive protein is mainly a cytosolic protein. When these MoAbs were tested in a previously established ELISA with intact mycobacteria derived from early cultures, only MoAb A3h4 showed the positive reactivity to mycobacteria belonging to the M. tuberculosis complex. In addition, during the present comparative studies of MoAbs we have also found that the previously described MoAb F116-5, which is known to recognize the mycobacterial 23-kDa SOD protein [17], cross reacted with the MPT44, MPT59, MPT45 and MPT51 secreted proteins but not with MPT64 and MPB70. These findings indicate that the family of four secreted proteins of M. tuberculosis share a common epitope with M. tuberculosis SOD protein. PMID- 8469932 TI - Low prevalence of complement deficiencies among patients with meningococcal disease in Norway. AB - Sera from 98 individuals who had survived meningococcal disease were analysed for classical and alternative pathway haemolytic activity and the complement components C3, C4 and properdin. No complete deficiency was found. However, median properdin concentration was only 86% in the disease group compared with the controls (P < 0.001). Properdin was also significantly lower in serogroup C disease (median 76%) compared with serogroup B disease (median 90%, P = 0.005). Severe properdin deficiency is an established risk factor for meningococcal disease. The present data may indicate that even moderately reduced properdin level can increase the risk of developing meningococcal disease. PMID- 8469933 TI - Linkage disequilibrium within the HLA complex does not extend into HLA-DP. AB - It is well known that certain alleles from different loci within the Human Leucocyte Antigen (HLA) complex are in linkage disequilibrium. This linkage phenomenon is relatively well characterized for haplotypes that include specific class I and class II alleles such as HLA-B8 and HLA-DR3. However, the HLA-DP genes are located at the centromeric end of the HLA complex and are less well characterized with regard to linkage disequilibrium. The availability of a large population of healthy subjects and sequence-specific oligonucleotide (SSO) typing enabled us to assess the degree of linkage between HLA-DPB1 and HLA-DQB1 genes. Using the polymerase chain reaction and a series of oligonucleotide probes which define seven DQ beta alleles and twenty DP beta alleles, we studied 180 unrelated, normal Caucasian individuals and found only weak or negative associations between HLA-DPB1 and HLA-DQB1. These data demonstrate that the association between HLA-DQ and DP is weak and also imply that DP extended haplotypes related to particular diseases may not reflect normal associations. Implications of these results might impact on the concept of linkage disequilibrium in general as well as the evolution of the HLA complex. In addition, extensions of this work may have clinical ramifications with regard to bone marrow transplantation and founder effects in certain diseases. PMID- 8469934 TI - Characterization of two highly homologous autoantibody-related VH1 genes in humans. AB - Previously, we showed that the Humha 1lr rearranged gene was almost identical to the consensus amino acid sequence of several G6 idiotype-positive rheumatoid factor (RF) heavy chains, and to the VH gene-encoded region of the fetally expressed 51P1 cDNA. The finding led us to suggest that the ha 1lr-corresponding germline gene encodes the heavy chains of many human IgM RFs. We now report the isolation of the proposed germline gene, designated Humhv1051; it is identical to the consensus sequence of the G6 heavy chain V regions. During this experiment, we also isolated unexpectedly an additional VH1 gene, termed Humhv1051K; it differs from hv1051 by one amino acid residue. Importantly, hv1051K is identical to Humha113, the rearranged VH1 gene of a natural anti-cardiolipin antibody. PMID- 8469935 TI - Transfer of CD8+ T cells into SCID mice and activation of memory virus-specific cytotoxic T cells. AB - The requirements for the activation of naive and memory CD8+ cytotoxic T (Tc) cells into effector virus-specific Tc cells after transferring them into SCID mice were investigated. SCID mice reconstituted with splenocytes or purified CD8+ T cells from naive or influenza-immune syngeneic mice and immunized with influenza virus generated effector Tc cells specific for influenza virus-infected target cells in vitro. The kinetics of the response varied between those two populations. The generation of effector Tc cells after transfer of memory CD8+ T cells indicates that there exists no absolute requirement for 'help' in the activation of memory virus-immune T cells. However, under the conditions described here the in vitro immunogenic peptide NPP derived from influenza nucleoprotein is not sufficient to elicit a response in vivo. PMID- 8469936 TI - Activated natural killer cells suppress myelopoiesis in mice with severe combined immunodeficiency. AB - The in vivo effect of natural killer (NK) cell activation on autologous myelopoiesis was studied in an environment deficient of functional T and B cells. Administration of 3,6-bis[2-(Dimethylamino)-ethoxy]-9H-xanthen-9-one dihydrochloride) Tilorone) or recombinant interleukin-2 (rIL-2) to mice with severe combined immunodeficiency (C.B.-17 scid/scid) resulted in an increase in YAC-1 lysis by their splenocytes as well as bone marrow cells. Recombinant IL-2 furthermore led to a fivefold increase in the cellularity of the spleen. When assayed against human NK/lymphokine-activated killer (LAK) target, K562 cell line, the IL-2-activated mouse cells exhibited no cytotoxicity across the species barrier. Both agents induced a profound suppression of myelopoietic progenitor cells as measured in a 7-day granulocyte-macrophage colony forming cell (GM-CFC) assay. We conclude that the presence of neither functional T nor B cells is necessary for NK cells to mediate inhibition of myelopoiesis in the autologous host. PMID- 8469937 TI - Incidence density is no density. PMID- 8469938 TI - Secular trends in the effect of socio-economic factors on birth weight and infant survival in Sweden. AB - Time trends in the effect of socio-economic factors on low birth weight, stillbirth, perinatal deaths and deaths up to the age of one were studied using a medical birth registry linked to census information from 1975, 1980, and 1985. For each census year, delivery outcome the following year was studied. Two socio economically different groups of women were studied, defined by occupation/education, cohabitation, and citizenship--one privileged and one under privileged group. A difference in birth weight distribution was found between the two groups which is only partly explainable by different smoking habits in early pregnancy and did not substantially change during the ten year observation period. In 1976, there was virtually no difference in infant mortality between the two groups. In 1981 and 1986, infant mortality had decreased in both groups but more strongly so in the privileged group, and a difference between the groups therefore appeared. PMID- 8469939 TI - Temporal and regional trends in fatal childhood injuries in Norway 1971-1989. AB - The paper focuses on how mortality due to injuries among Norwegian children has varied over time and throughout the country over the last two decades. The temporal trends are compared to those of the other Nordic countries. Individual data on date of birth and death, county of residence at death, sex and cause of death were obtained from the Norwegian Death Registry on all children aged 0-14 who died during the time-span 1971-1989. Denominators were the number of persons alive in the corresponding age, year, sex and county groups. There has been a decline in fatal injuries from 25 to 9 deaths per 100,000 person-years in, respectively, 1971 and 1989. The decline is less distinct in the late 1980's. The rate of fatal injuries have throughout the period been lowest in the county of Oslo and highest in Northern Norway with fatal injury rates in Finnmark 3 times that of Oslo. The declining time trend was present for all types of injuries except bicyclists and passengers, but with the sharpest decline for pedestrians and drowning injuries. The regional variation was strongest for drowning and showed a different profile from the overall pattern for bicyclists, passengers and falling injuries. The incidence of fatal injuries in Norway is comparable to those of Denmark, Finland and Iceland, but considerably higher than in Sweden. In all Nordic countries the rates have declined to about one third from 1971 to 1988. PMID- 8469940 TI - The relation between teenage smoking and drinking, with special reference to non standard family background. AB - Associations between simultaneous teenage drinking and smoking are considered in a birth cohort born in Northern Finland in 1966 (n = 12,058), especially in non standard, mainly single parent families. Data were collected from pregnancy until the age of 14. ROC (receiver operating characteristic curve) analysis was used to assess how well smoking predicts use of alcohol. Smoking and drinking were more interconnected in the non-standard families among both boys (p = 0.007) and girls (p = 0.018), but only among boys (p = 0.064) when the data were standardized for social class and place of residence and not among girls (p = 0.191). A similar relation between smoking and having been drunk was found among boys in non standard families (p = 0.016), even when adjusted as above (p = 0.029), but not among girls (unadjusted p = 0.235, adjusted p = 0.469). The findings suggest that the adolescent boy's self-protective behaviour with respect to the commencement of combined experimentation with smoking and drinking is more restricted in non standard families than in standard families. PMID- 8469941 TI - Validity of register data on acute myocardial infarction and acute stroke: the Skaraborg Hypertension Project. AB - In the evaluation of a hypertension treatment program, the end-point surveillance included incidence of acute myocardial infarction and acute stroke identified from hospital in-patient registers and the national mortality register. To ascertain the validity, in-patient records containing the ICD-codes 410-411 and 430-438 were validated. First event of acute myocardial infarction and acute stroke suggested in the in-patient register could be confirmed in 96% and 94%, respectively. In-patient diagnoses of suspected acute myocardial infarction or other acute or subacute ischemic heart diseases, transient ischemic attack and unspecified heart diseases, transient ischemic attack and unspecified cerebrovascular disease revealed high proportions of what in fact turned out to be definite events (11%, 24% and 53% respectively). It is concluded that disease ascertainment for this cohort study claims validation of register data with hospital records. PMID- 8469942 TI - Initiation into drug abuse: the pathway from being offered drugs to trying cannabis and progression to intravenous drug abuse. AB - The aim of the study was to analyse the initiation process into illicit drug use focusing on three endpoints which can be seen as stages in the drug career: being offered drugs, using cannabis and using intravenous drugs. Questionnaire data were available on 23,482 men, aged 18-20 years, conscripted for military service in 1969-70. The association between family background, social conditions, other illicit drug use, emotional control and the three endpoints were analysed. Although many conscripts tried cannabis, a smaller number continued with intravenous drug abuse. These were in general characterised by poor emotional control and a history of social maladjustment, and early onset of use. Our findings give further evidence for social maladjustment as a causative factor for illicit drug use and for the role of cannabis as a stepping stone to heavy drug abuse. PMID- 8469943 TI - Determinants of health care utilization--visits and referrals. AB - This study explores determinants of I) general practitioner (GP) visits and II) referrals (outpatient and hospitalization). The analyses were performed with regression models on a set of data from a comprehensive population study of 3533 men and 3578 women aged 40-42 in a county in Northern Norway. Among the various health status dimensions included, self-rated health was found to be the most important determinant, regardless of type of service. Factors, other than health status aspects affecting GP visits, were preoccupation with health and help seeking attitude. Volume of resources (GP per population), socio-demographic characteristics and social networks did not appear as important. Several inequitable effects were revealed on referrals: First, higher rate of referral of patients with higher educational achievement indicates a bias towards higher social status groups. Second, high GP/population ratio and residence in municipalities with referral care facilities were both found to be associated with higher probability of referral. PMID- 8469944 TI - Differences in the diagnose panorama in primary health care in Dalby, Sweden and Spili, Crete. AB - We have compared the use of primary health care and the diagnoses at visits to doctors in the Spili Health Centre (SHC) in Crete and the Dalby Health Centre (DHC) in Sweden. In DHC more patients per 1000 population visited the doctors than in SHC. This was so regardless of age-group and sex, in fact more or less regardless of diagnosis. Other differences between the populations were: The diagnosis acute otitis media was more frequent in the Dalby children than in the Spili ones. The opposite was true of "head injuries" which were more frequent in the Spili boys. Visits to doctors for bronchitis was more frequent in the Spili men, maybe because of the extensive smoking habits of Cretan men. Visits for diseases of the musculoskeletal system were more frequent in DHC than in SHC. A hypothesis worth testing is that this was influenced by differences in the health insurance and sick benefit systems. Angina pectoris was fairly frequent in both areas but cardiosclerosis (including healed myocardial infarction) was more common in DHC than in SHC. Use of primary health care may be influenced by the need for health care in the population, the accessibility of the health care facilities, the costs for the patients, the quality of care as perceived by the patients and by other sociocultural factors. Comparative studies, even though fairly uncommon today, may be of use in generating hypotheses about the impact of different factors on the use of health care. PMID- 8469945 TI - [Interference versus low frequency. A comparison of 2 methods of electric muscle stimulation]. AB - The purpose of this study was to determine whether inferential or low-frequency stimulation can produce a stronger and less painful contraction of the quadriceps femoris muscle in 20 healthy subjects. Both currents used a pulse rate of 50 Hz. The perceived discomfort experienced with each type of electrical stimulation was quantified by the use of a visual analogue scale. An isokinetic dynamometer (Cybex) was used to assess peak torque. Paired t-test demonstrated that inferential stimulation was perceived to be significantly less uncomfortable than low-frequency stimulation and that inferential stimulation produced a significantly greater peak torque of muscle contraction than low-frequency stimulation. This study indicates that inferential stimulation can produce an electrically induced muscle contraction which is stronger and less unpleasant than low-frequency stimulation. PMID- 8469946 TI - [Selenium metabolism and glutathione peroxidase activity of endurance athletes in rest and under exertion]. AB - Selenium which has been recognised as an essential trace element for mammals and humans is part of the enzyme glutathione peroxidase (GSHPx) and of other selenium dependent enzymes. GSHPx protects the organism from oxidative damage. Supposing that the formation of peroxides is enhanced in athletes during a marathon run the question arose whether the selenium concentrations in the blood plasma and the GSHPx activities in the erythrocytes are changed. Our experiments were performed with 13 athletes completing a marathon. Blood probes were taken before, immediately after and two hours after the endurance event. No significant changes in the selenium concentrations of the blood plasma probes nor of the enzyme glutathione peroxidase activities of the erythrocytes were observed during the experiments. The selenium concentrations in the plasma: 77.7 +/- 20.8 micrograms/l and the GSHPx activities of the erythrocytes 18.2 +/- 7.4 U/g Hb were within normal clinical range. Symptoms of selenium deficiency could not be detected. In order to answer the question of whether the selenium concentrations in the blood of the athletes represent an optimal level for preventing enhanced formation of peroxides, intervention studies are needed, including measurement of more parameters of lipid peroxidation. PMID- 8469947 TI - [Fasting and physical endurance capacity]. AB - Fasting, or zero calorie diets are used not only by overweight people as a means of losing weight, but by athletes too. Their use is then explained on philosophical grounds, with the aim of even enhancing sports performance. The purpose of this investigation consisted of quantifying the effects of a 10-day fast on maximum performance capacity and endurance (as measured on a bicycle ergometer) of 12 female students of physical education of normal weight. The measurements included resting and exercise metabolism determinants, as well as weight and lean body mass. The main results show that after the diet period the maximum ergometric performance was lower in absolute terms as well as in relation to weight or lean body mass. Performance capacity for submaximal exercise was also reduced. Fat combustion was enhanced both at rest and during exercise. The reduction of maximum performance and endurance capacity may be explained by an enhanced muscle breakdown, an efficiency drop of muscular work, and an inadequate glycogen content of the acting muscles. Shorter fasting periods of 24-36 hours also lead to a lower performance level for exercise bouts extending from several minutes to 1-3 hours. An enhancement of fat combustion was always conspicuous. One may conclude that optimal physical performance is dependent on full hepatic and muscle glycogen stores. Glycogen concentration in the liver decreases sharply as a matter of fact after merely one day of carbohydrate shortage. Zero calorie or low carbohydrate diets are thus at variance with an optimal physical work capacity. PMID- 8469948 TI - [Does drinking protect against mountain sickness?]. AB - This paper summarizes the main findings of 3 publications of our group [2-4] examining fluid balance at high altitude. Of 57 mountaineers ascending from 1170 m to 4559 m within 22 to 77 hours, 24 developed acute mountain sickness (AMS) and 16 developed high altitude pulmonary edema (HAPE). In 14 cases HAPE was preceded by symptoms of AMS. Independently of the amount of fluid intake, which varied from 2 to 4 l/24 h in these studies, subjects developing AMS showed decreased diuresis and natriuresis compared to healthy controls with similar fluid intake. Higher fluid intake resulted in greater urine output but did not prevent AMS. Higher plasma levels of aldosterone at rest and greater exercise-induced rises of plasma aldosterone and vasopressine may explain the increased water and salt retention in subjects with AMS. Whether these hormonal changes are secondary to a more severe hypoxemic stress or present a primary cause of AMS remains to be determined. PMID- 8469949 TI - Environmental radiochemical analysis. A collection of papers from the 6th International Symposium on Environmental Radiochemical Analysis, September 1990, Manchester, UK. PMID- 8469950 TI - Implementation of a radiochemical procedure for the analysis of isotopes of Pu, Am and Cm in food and environmental samples. AB - A radiochemical procedure for the analysis of isotopes of Pu, Am and Cm was implemented during an expert mission to Thailand sponsored by the International Atomic Energy Agency. This method was to be used for the analysis of food and environmental samples, particularly those of marine origin. The project was initiated by evaluating a procedure which had recently been published by the IAEA. This procedure could not handle the wide range of matrix materials used in the testing and a program was undertaken to develop a modified procedure. Plutonium was radiochemically separated using an anion exchange procedure which gives clean separations from the matrix. Americium and curium came off the column unseparated from most of the other elements in the matrix and they were separated by using a number of steps, which were selected to handle the specific chemical and radiochemical interferences in a particular matrix material. Sources were prepared for alpha spectrometry by coprecipitation with CeF3. The procedure was tested with a wide variety of sample types and good chemical yields and separations were obtained in most cases. PMID- 8469951 TI - A rapid method for monitoring of uranium and radium in drinking water. AB - A time-saving and fairly accurate method for monitoring U and 226Ra in drinking water has been devised, using low-background liquid scintillation spectrometry and pulse-shape analysis. The samples are prepared for counting by evaporating water in a liquid scintillation vial. The residue is dissolved in 1 ml of 0.5 N HCl, and a scintillation cocktail is added. Counting is carried out twice: a few days and a month after the sample preparation using the Quantulus, a liquid scintillation spectrometer equipped with a guard counter and pulse-shape analyser. The counter produces separate alpha and beta spectra which enable calculation of the approximate U and 226Ra contents. These correlate well with the results obtained by radiochemical methods. The measured spectra give valuable information on the nuclide content, e.g. increased U, 226Ra, 210Pb and 210Po activities, and on the 234U: 238U activity ratio in the water. This kind of information is very valuable in deciding on the necessity for time-consuming radiochemical analyses for radiation protection purposes or exploration for U ore deposits. In many cases the results from the Quantulus are sufficient to determine the U and 226Ra levels in drinking water. The lower limits of detection for U and 226Ra are 0.02 and 0.01 Bq/l, respectively, when the counting time is 180 min and the sample volume 38 ml. PMID- 8469952 TI - The analysis of naturally-occurring radionuclides from uranium and thorium decay series in table mineral waters. AB - This project required the highly sensitive analysis of low-level alpha- and beta emitters naturally occurring in table mineral water sold on the Swiss market. These radionuclides occur in the three major decay series-uranium-238, uranium 235, and thorium-232. The radionuclides analysed were 238U, 235U, 234U, 232Th, 230Th, 228Th, 210Po, 210Pb, and 226Ra. Many other radionuclides were determinable as a result of their equilibrium with an analysed nuclide. Efficient, element specific separation techniques were developed, allowing for the spectral analysis of each element without interference from other radioactive elements. Radioactive tracers, 232U, 230Th, and 209Po, were necessary to determine the percentage yield. These yields often varied greatly between different mineral waters, especially for thorium, ranging from 30 to 100%. Uranium, thorium and polonium isotopes could be directly analysed for by alpha-spectrometry. 226Ra was determined through the ingrowth of its daughter 222Rn by liquid scintillation counting. From the samples remaining after 210Po removal, the isotope's re ingrowth from 210Pb determined the original 210Pb content. Limits of detection ranged from 0.1 to 2.0 mBq/l. The following contents were determined 234U + 238U 30-720 mBq/l; 232Th + 230Th < 1-5 mBq/l; 228Th 2-40 mBq/l; 226Ra 5-370 mBq/l; 210Po 1-90 mBq/l; 2,0Pb 1-90 mBq/l. PMID- 8469953 TI - Environmental and personnel monitoring for uranium by delayed neutron counting. AB - At the Imperial College Reactor Centre we have developed a fully automated, large sample, high sensitivity delayed neutron counting system for routine analysis of environmental samples and personnel monitoring. Two-hundred fifty samples with a maximum volume of 30 ml can be analysed each working day. The detection limits (3 sigma) for uranium of natural isotopic abundance in our routine samples are typically 1 microgram/kg (0.05 Bq/kg) for dry samples and 1 microgram/l (0.05 Bq/l) for aqueous samples. Daily analysis of BNFL uranium standards, 'in house' uranium standards and weekly analysis of IAEA Soil-7 reference material are used to ensure constant system sensitivity and accuracy. PMID- 8469954 TI - The determination of tritium, 14C and 35S in milk and crop samples using a combustion technique. AB - The use of a combustion technique for the determination of low energy beta emitting radionuclides in solid and liquid samples has been in widespread use for a number of years. However, the sensitivity of measurements by existing commercially available combustion apparatus has been limited by the amount of sample that can be combusted before incorporating the combustion products into a liquid scintillator for subsequent counting. Consequently the determination of tritium, 14C and 35S at environmental levels has not been possible using commercially available equipment. This paper describes the apparatus and method that was developed at the Central Veterinary Laboratory for the determination of these low energy beta-emitters in milk and crop samples. A typical sample size of 20-50 g is routinely measured, although the apparatus is designed to be able to make several sequential combustions before measurement of the oxidation products by liquid scintillation counting. PMID- 8469955 TI - Production of a spiked milk reference material. AB - A spiked milk reference material containing 134Cs and 137Cs has been successfully produced. The material has been characterised in a manner directly traceable to national standards of radioactivity. This work is part of a EUROMET project to produce spiked reference materials at a range of densities from 0.1 to 2.0 g/cm3. PMID- 8469956 TI - Measurements of the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium in experimental animals. AB - In order to set limits on environmental and occupational intakes of radionuclides, information is needed on their uptake and metabolism in man. Human data are very limited, particularly for long-lived alpha-emitting isotopes such as those of the actinides. Animal experiments are therefore an important source of data on the distribution of radionuclides in tissues, and the effects of factors such as subject age and the chemical form of elements on gastrointestinal absorption. The NRPB performs experimental programs using mainly rats and guinea pigs. In order to study the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium, a variety of analytical techniques are employed. These include ion exchange and solvent extraction leading to alpha spectrometry and liquid scintillation counting. The investigation of low specific activity environmental or industrial materials, and the very low bioavailability of elements such as the actinides, means that very low levels of activity have to be measured. Contamination at the dissection and tissue separation stage, as well as during the radiochemistry, has to be rigorously avoided. Where very detailed information is needed on the location of radionuclides within tissues, such as in the study of alpha-emitter distribution in the intestine, autoradiography is used. The application and relevance of different measurement techniques to animal studies will be discussed and examples of the results presented. PMID- 8469957 TI - Radon concentration levels in ground water from Toluca, Mexico. AB - Concentration levels of 222Rn have been analysed in water samples from deep wells of the aquifers around the City of Toluca, Mexico. The 222Rn source is the decay of 226Ra within the solid matrix of the aquifer. With a half life of 1600 years the 226Ra continuously releases 222Rn to the pores, from which it diffuses into the main body of water. This paper describes the methods used for sampling and measuring solubilized and 226Ra-supported 222Rn in the water samples, in order to evaluate possible health hazards due to the presence of radon in the drinking water supplies. The relationship of 222Rn with the hydrogeologic characteristics of the zone is also described. The analytical method involves laboratory extraction of 222Rn into toluene. Alpha disintegrations of 222Rn and contributions from short-lived daughters are counted by the liquid scintillation technique. The system was calibrated using a 226Ra standard solution. Results up to 11.3 Bq/l of 222Rn were obtained in the water samples. PMID- 8469958 TI - Use of liquid scintillation counting for fast determination of 89Sr and 90Sr in milk. AB - This paper describes a method of reproducibly recovering strontium (Sr) in 90.4% yield from 2-litre samples of raw milk in an analysis time of 5-8 h. All species which may interfere with the measurement of 89Sr and 90Sr are effectively removed; decontamination factors for Ca, Y, Ba and Cs were found to be adequate, and the role of other possible interferences is discussed. The Sr isolate was dissolved in scintillation cocktail prior to counting of 89Sr and 90Sr in a single measurement with a low-level liquid scintillation spectrometer. Scintillation spectra and counting efficiencies for 89Sr, 90Sr and 90Y have been established. A simple spectral stripping technique may thus be applied to calculate activities from the spectra of real samples. Results of analyses of five 2-1 milk samples containing known activities of 89Sr and 90Sr were respectively 87.7 +/- 3.5% and 90.4 +/- 3.0% (+/- 1 S.D.) of the activities added. A correction factor for the Sr yield was not applied. The detection limit of 0.014 Bq for 90Sr samples free of 89Sr implies that the method is also useful for routine monitoring of 90Sr. PMID- 8469959 TI - Recent results (1986-1989) on the ENEA quality assurance programme for the radioactivity surveillance network in Italy. AB - A programme for the Quality Assurance of the Italian network for surveillance of radioactivity in foodstuff and environmental samples was started by the ENEA in 1983. The main purpose of this programme is to establish uniform levels of accuracy and reproducibility in measurement procedures routinely used by the laboratories belonging to the network. This paper describes the technical aspects relevant to the calibration and intercomparison campaigns carried out, in Italy, in the period 1986-1989. The relevant measurements include gamma spectrometry and beta-ray counting in liquid aqueous samples. PMID- 8469960 TI - Radiotoxicological intercomparisons organised by the Commissariat a l'Energie Atomique group in France. AB - People working in French nuclear plants are monitored either by whole body counting or by the measurement of biological samples. The radiochemical and radiometric procedures used have to be periodically reviewed. A working group, including practising biologists from CEA, EDF and the Armed Forces Health Service, instituted comparisons of radiotoxicological test assessments. Since 1978, about 60 intercomparisons have been made. Currently 30 European laboratories are involved in these intercomparisons. This paper provides a brief history of the intercomparison exercises, describes the logistics of sample collection and preparation, and presents the results, showing the position of each laboratory in relation to the reference and median values. Diagrams produced by radiochemical analysis, relating to plutonium in urine and in faecal samples, and to tritium, strontium and enriched uranium in urine, are analysed. PMID- 8469961 TI - The distribution of 210Po in human bone. AB - Recent measurements of natural radioactivity in human bone using alpha particle autoradiography have indicated that the alpha activity concentration in the bone marrow is similar to that found in the calcified bone. This paper describes radiochemical measurements made on the calcified bone and the associated bone marrow from three human femurs. A technique was developed to separate and analyse these tissues for the principal naturally-occurring alpha emitter, 210Po. In all cases the activity concentration of the calcified bone was greater than that of the associated bone marrow. As predicted by the metabolic models used by International Commission on Radiological Protection, the majority of the 210Po in whole bone was found to be in the calcified region. PMID- 8469962 TI - Caesium radioactivity in several selected species of honey. AB - In the years following the accident to the nuclear power plant at Chernobyl, investigations on several selected species of honey were done to determine their 134,137Cs contamination. Very low caesium activities were found in flower honeys, especially rape honeys. The transfer factor of caesium from the soil to the rape plant (Brassica napus var. oleifera) was found to be fCs = 0.116 +/- 0.080 in 1987, but only fCs = 0.017 +/- 0.017 in 1988, due to the lower availability of the caesium by gradual formation of water-insoluble chemical species. Honeydew honeys show a slightly higher 134,137Cs contamination. Honeydew is often produced by lice setting on spruces. Therefore, needles and twigs of spruces (Picea abies) were investigated and relatively high caesium contamination was found in fresh needles. A transfer factor for caesium from spruce needles to honeydew honey of about 0.1 was estimated. Finally, the caesium contamination in heather honeys and heather plants (Calluna vulgaris) was determined. Surprisingly higher factors between 2 and 40 were obtained for the caesium transfer from soil to Calluna vulgaris. These factors give a good explanation for the relatively high caesium contamination of heather honeys. PMID- 8469963 TI - No lack of NO activity. PMID- 8469964 TI - No lack of NO activity. PMID- 8469965 TI - Genome project plans described. PMID- 8469966 TI - Early AZT takes a pounding in French-British 'Concorde' trial. PMID- 8469967 TI - New AIDS research center to open. PMID- 8469968 TI - Ulcers as an infectious disease. PMID- 8469969 TI - Evolution. Why some fishes are hotheads. PMID- 8469970 TI - Biologists visit New Orleans (under an assumed name) PMID- 8469971 TI - Measuring single protein motors at work. PMID- 8469972 TI - Electrostatic screening of charge and dipole interactions with the helix backbone. AB - Electrostatic interactions in proteins are potentially quite strong, but these interactions are mitigated by the screening effects of water, ions, and nearby protein atoms. The early work of Kirkwood and Westheimer on small organic molecules showed that the extent of the screening may depend on whether charged or dipolar groups are involved. The dielectric and ionic screening of the interactions between the dipolar backbone amide groups of monomeric alpha helices and either (i) solvent-exposed charges or (ii) solvent-exposed dipoles at the amino terminus was measured. The dielectric screening effects are an order of magnitude greater for the backbone-charge interactions than for the backbone dipole interactions, and the ionic strength dependence is substantially different in the two cases. These results suggest that interactions that involve the dipolar groups of proteins may be relatively more important for stability and function than is generally thought. PMID- 8469973 TI - Impairment of V(D)J recombination in double-strand break repair mutants. AB - Cells maintain the integrity of their genome through an intricate network of repair systems that recognize and remove lesions from DNA. The only known site directed recombination process in vertebrates is the V(D)J recombination of lymphocyte antigen receptor genes. A large panel of cell lines deficient in DNA repair were tested for the ability to perform V(D)J recombination after introduction of the RAG-1 and RAG-2 genes. Two mutants failed to generate normal V(D)J recombination, and further analysis provided evidence for two distinct nonlymphoid-specific genes that encode factors involved in both DNA repair and V(D)J recombination. PMID- 8469974 TI - Evolution of endothermy in fish: mapping physiological traits on a molecular phylogeny. AB - Mackerels, tunas, and billfishes (suborder Scombroidei and Teleostei) provide an ideal taxonomic context in which to examine the evolution of endothermy. Multiple origins and diverse strategies for endothermy exist among these fish. Here a molecular phylogeny of the Scombroidei has been determined by direct sequencing of a portion of the mitochondrial cytochrome b gene. The distribution of endothermic species within this proposed genealogy indicates that the ability to warm the brain and retina arose independently in three lineages, each time in association with a movement into colder water. This suggests that the evolution of cranial endothermy in fish was selected in order to permit thermal niche expansion and not selected for increased aerobic capacity. PMID- 8469975 TI - Force of single kinesin molecules measured with optical tweezers. AB - Isometric forces generated by single molecules of the mechanochemical enzyme kinesin were measured with a laser-induced, single-beam optical gradient trap, also known as optical tweezers. For the microspheres used in this study, the optical tweezers was spring-like for a radius of 100 nanometers and had a maximum force region at a radius of approximately 150 nanometers. With the use of biotinylated microtubules and special streptavidin-coated latex microspheres as handles, microtubule translocation by single squid kinesin molecules was reversibly stalled. The stalled microtubules escaped optical trapping forces of 1.9 +/- 0.4 piconewtons. The ability to measure force parameters of single macromolecules now allows direct testing of molecular models for contractility. PMID- 8469976 TI - Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. AB - The myotonic dystrophy mutation has recently been identified; however, the molecular mechanism of the disease is still unknown. The sequence of the myotonin protein kinase gene was determined, and messenger RNA spliced forms were identified in various tissues. Antisera were developed for analytical studies. Quantitative reverse transcription-polymerase chain reaction and radioimmunoassay were used to demonstrate that decreased levels of the messenger RNA and protein expression are associated with the adult form of myotonic dystrophy. PMID- 8469977 TI - Women in science. PMID- 8469978 TI - Nuclear structure research. PMID- 8469979 TI - Clinton's mixed broth for R&D. PMID- 8469980 TI - MicroGeneSys: NIH faces down DOD. PMID- 8469981 TI - NIH fraudbusters get busted. PMID- 8469982 TI - Volcanologists ponder a spate of deaths in the line of duty. PMID- 8469983 TI - AIDS research. Keystone's blunt message: 'it's the virus, stupid'. PMID- 8469984 TI - Methylation and imprinting: from host defense to gene regulation? PMID- 8469985 TI - Monophyletic origins of the metazoa: an evolutionary link with fungi. AB - A phylogenetic framework inferred from comparisons of small subunit ribosomal RNA sequences describes the evolutionary origin and early branching patterns of the kingdom Animalia. Maximum likelihood analyses show the animal lineage is monophyletic and includes choanoflagellates. Within the metazoan assemblage, the divergence of sponges is followed by the Ctenophora, the Cnidaria plus the placozoan Trichoplax adhaerens, and finally by an unresolved polychotomy of bilateral animal phyla. From these data, it was inferred that animals and fungi share a unique evolutionary history and that their last common ancestor was a flagellated protist similar to extant choanoflagellates. PMID- 8469986 TI - Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii. AB - Toxoplasma gondii is a protozoan pathogen that produces severe disease in humans and animals. This obligate intracellular parasite provides an excellent model for the study of how such pathogens are able to invade, survive, and replicate intracellularly. DNA encoding chloramphenicol acetyltransferase was introduced into T. gondii and transiently expressed with the use of three vectors based on different Toxoplasma genes. The ability to introduce genes and have them efficiently and faithfully expressed is an essential tool for understanding the structure-function relation of genes and their products. PMID- 8469987 TI - Structure of DNA polymerase I Klenow fragment bound to duplex DNA. AB - Klenow fragment of Escherichia coli DNA polymerase I, which was cocrystallized with duplex DNA, positioned 11 base pairs of DNA in a groove that lies at right angles to the cleft that contains the polymerase active site and is adjacent to the 3' to 5' exonuclease domain. When the fragment bound DNA, a region previously referred to as the "disordered domain" became more ordered and moved along with two helices toward the 3' to 5' exonuclease domain to form the binding groove. A single-stranded, 3' extension of three nucleotides bound to the 3' to 5' exonuclease active site. Although this cocrystal structure appears to be an editing complex, it suggests that the primer strand approaches the catalytic site of the polymerase from the direction of the 3' to 5' exonuclease domain and that the duplex DNA product may bend to enter the cleft that contains the polymerase catalytic site. PMID- 8469988 TI - Requirement for tyrosine kinase p56lck for thymic development of transgenic gamma delta T cells. AB - The Src-related protein tyrosine kinase p56lck is essential for antigen-specific signal transduction and thymic maturation of T cells that have an alpha beta T cell receptor (TCR), presumably by physical association with CD4 or CD8 molecules. To evaluate the requirement for p56lck in the development of T cells that have gamma delta TCRs, which generally do not express CD4 or CD8, p56lck mutant mice were bred with TCR gamma delta transgenic mice. Few peripheral cells that carried the transgenes could be detected in p56lck-/- mice, although 70 percent of thymocytes were transgenic. Development of transgenic gamma delta+ thymocytes was blocked at an early stage, defined by interleukin-2 receptor alpha expression. However, extrathymic development of CD8 alpha alpha+ TCR gamma delta+ intestinal intraepithelial lymphocytes appeared to be normal. Thus, p56lck is crucial for the thymic, but not intestinal, maturation of gamma delta T cells and may function in thymic development independently of CD4 or CD8. PMID- 8469989 TI - Tumor cell growth arrest caused by subchromosomal transferable DNA fragments from chromosome 11. AB - A fundamental problem in the identification and isolation of tumor suppressor and other growth-inhibiting genes is the loss of power of genetic complementation at the subchromosomal level. A direct genetic strategy was developed to isolate subchromosomal transferable fragments (STFs) from any chromosome, each containing a selectable marker within the human DNA, that could be transferred to any mammalian cell. As a test of the method, several overlapping STFs from 11p15 were shown to cause in vitro growth arrest of rhabdomyosarcoma cells. This activity mapped between the beta-globin and insulin genes. PMID- 8469990 TI - Neuronal differentiation rescued by implantation of Weaver granule cell precursors into wild-type cerebellar cortex. AB - The migration of postmitotic neurons away from compact, germinal zones is a critical step in neuronal differentiation in the developing brain. To study the molecular signals necessary for cerebellar granule cell migration in situ, precursor cells from the neurological mutant mouse weaver, an animal with phenotypic defects in migration, were implanted into the external germinal layer (EGL) of wild-type cerebellar cortex. In this region, labeled weaver precursor cells of the EGL progressed through all stages of granule neuron differentiation, including the extension of parallel fibers, migration through the molecular and Purkinje cell layers, positioning in the internal granule cell layer, and extension of dendrites. Thus, the weaver gene acts nonautonomously in vivo, and local cell interactions may induce early steps in neuronal differentiation that are required for granule cell migration. PMID- 8469991 TI - Socioeconomic forces affecting medicine: times of increased retrenchment and accountability. AB - Costs of health care are increasing at a rapid rate, but both access to care and costs of care have become focal points for current national and local debates. Access issues relate not only to those who have no insurance but also to those who are underinsured. Cost issues relate most directly to radiology and nuclear medicine through their impact on coverage and payment. Increasing scrutiny is paid to criteria used for these purposes, and major changes at the federal and private level can be expected in the next decade. Finally, the ubiquitous development of practice guidelines and their expected use in physician profiles will influence the practice of medicine significantly in the future. PMID- 8469992 TI - Work force problems in nuclear medicine and possible solutions. AB - Nuclear medicine practice and work force demographics reflect the historically diverse evolution of this specialty. The most pressing problem for nuclear medicine is a projected shortage of fully trained physicians due to practitioner retirement that is unmatched by residency program output. During the past decade the number of 2-year nuclear medicine residency programs (average of 90) and the total number of residents (average of 191 in both years) have remained remarkably stable. In contrast, the number of 1-year nuclear radiology residency programs, available positions, and residents have declined significantly. A similar decline is seen in radiologists obtaining full nuclear medicine training and American Board of Nuclear Medicine (ABNM) board certification. This void has been filled by nonradiologist trainees who only seek certification by ABNM. Perhaps such shifts in resident profile are an early indicator that the United States is evolving toward practice models in which nuclear medicine is provided by fully trained, full-time physicians, similar to the European work force model. The recent Society of Nuclear Medicine survey of 10,446 physicians who practice nuclear medicine shows a current practice pattern in the United States that is distinctly different from that in Europe. The vast majority of those surveyed practice part time. Only 7% of all physicians who practice nuclear medicine do so full time, (ie more than 90% of the time), but they account for as much full-time employee (FTE) work load as 70% of all part-time physicians. Although the number of radiologists entering nuclear medicine is declining, 51% of total FTE work load is still done by radiologists with only American Board of Radiology certification. Physicians certified by ABNM represent 42% of all FTE work load. Cardiologists certified by American Board of Internal Medicine-Cardiovascular Specialization account for approximately 4% of nuclear medicine (15% of total cardiovascular nuclear medicine) FTE work load. Work force shortage of nuclear medicine technologists remains a chronic problem in spite of extensive study: however, recent predictions suggest some improvement in the future. Solutions to work force problems facing nuclear medicine will require ongoing data surveys, aggressive recruitment of trainees, expansion of training positions, and socioeconomic initiatives that promote desirable future practice models. PMID- 8469993 TI - Nuclear medicine in private practice. AB - The private practice of nuclear medicine has evolved over the past decade. Federal and state regulatory agencies, reduction in reimbursement, and a shortage of qualified physicians and technologists will affect the practice of nuclear medicine in the 1990s and beyond. Only by being proactive and able to provide credible clinical information to our referring physicians can nuclear medicine position itself for the next decade. We must continue to educate referring physicians about the cost-effectiveness and functional and physiological nature of nuclear medicine. We need to encourage medical students and physicians in training to consider nuclear medicine as a career path, and we need to provide meaningful clinical information to our referral base. In addition to these challenges, we should also remember that nuclear medicine cannot survive in a vacuum. We must support our professional societies and have ongoing representation at all levels of government. Membership in the American Medical Association, the Society of Nuclear Medicine, the American College of Nuclear Physicians, the American College of Radiology, and the Radiological Society of North America all help strengthen our voice at the state and national levels. We must continue to effectively present our specialty's positions to the various state and federal agencies that regulate our practice. We must demand high quality studies from our peers and continue to be advocates for our patients. PMID- 8469994 TI - The potential impact of the resource-based relative value scale on the practice of nuclear medicine. AB - The Resource-Based Relative Value Scale (RBRVS) is finally here. A system designed to equate physician work across the specialties, it has its own peculiar and unique problems. Modeling of the system was based on the single physician patient interaction; it may not work properly for laboratory specialties. There are other unique considerations concerning how the model was constructed. Although data were collected specifically for nuclear medicine, they were not used in the final computations. There is disagreement over whether those data would benefit or hurt nuclear medicine reimbursement. As presently implemented, the RBRVS poses grave dangers for the future of nuclear medicine. These dangers come not only in the professional reimbursement section of the rules but in the technical component areas as well. Estimates for reduction of income by 1996 range as high as 55% for nuclear medicine. When one factors the implementation of the RBRVS by independent insurance carriers into the equation, the entire economic future becomes muddy. A brief historical review of the RBRVS, as well as discussion of potential future implications of this type of reimbursement system, is presented. Prognostication is at least as inexact a science as reimbursement. Hopefully, the author's outlook on the future of nuclear medicine is more pessimistic than it need be. PMID- 8469995 TI - Current procedural terminology coding of nuclear medicine procedures. AB - The future of nuclear medicine is dependent on payment for new procedures. Today, the basis of payment by the federal government is a relative value unit (RVU) system; the RVUS employed in this system are for medical services and procedures listed and described in Physicians' Current Procedural Terminology, fourth edition. Current procedural terminology (CPT) is maintained by the AMA; annual revisions include adding new codes or revised or deleted old codes. This process involves all national medical specialty societies. Starting in 1992 a new process, the Relative Updating Committee, which was initiated by the AMA, organized medicine to formalize a method for recommending relative values for physician procedures and services. In this rapidly changing scenario, all nuclear medicine procedure codes are under review by the coding and nomenclature committees of the medical societies interested in imaging. Significant CPT changes and additions were made in the cardiovascular nuclear medicine codes in 1992, reflecting the current imaging protocols and pharmacological agents for performing cardiac stress testing and new codes that recognize combinations of ventricular function measurements in patients undergoing myocardial perfusion imaging with technetium-99m agents. PMID- 8469996 TI - The practice of nuclear medicine in common market countries. AB - There is no politically structured European policy on nuclear medicine, and there are significant discrepancies between the various member states. It is hard to guess whether competing imaging modalities will slow down the process of development that took place in underequipped countries. But it appears likely that with the free circulation of professionals between European Community countries, free competition will stimulate these countries toward major development in nuclear medicine. PMID- 8469997 TI - Renal clearance determination with one blood sample: improved accuracy and universal applicability by a new calculation principle. AB - A sufficiently accurate quantification of renal function requiring only one plasma sample without an additional gamma camera study has until now only been possible in adults. A new principle has been developed that allows the universal application of known algorithms, irrespective of the clearance substance used, by normalizing the plasma concentrations with respect to individual body dimensions of adult as well as infant patients. In this respect, algorithms are established for clearance determinations using technetium-99m mercaptoacetyltriglycine which are based on steady-state studies as the reference. They allow the calculation of quantitative clearance values in infants and require the drawing of only one blood sample at any time between 25 and 40 minutes postinjection. The comparison with a combined-camera/two-plasma-sample technique performed in 46 children ranging in age from 9 days to 14 years (mean, 6.05 years) resulted in a standard deviation of 8.5% from the line of identity (r = 0.94). Moreover, this procedure also increases accuracy in adult patients, especially those with impaired renal function. PMID- 8469998 TI - Cost-effectiveness in nuclear medicine. AB - There are many pressures on nuclear medicine physicians to keep costs down and to produce the most efficacious results for the money spent. A procedure is cost effective if its benefits (correct diagnosis, effective treatment, etc.) are worth the additional costs (money, radiation dose, etc.). The benefits of diagnostic procedures are measured by test performance (diagnostic efficacy [efficacy-D]), which in turn depends on a specific task: detection, classification, localization, or quantitation. For the detection task, measures of test performance include sensitivity, specificity, predictive value, accuracy, diagnostic utility, posttest versus pretest disease probability, area under a receiver operating characteristic (ROC) curve, and others. Standard measures of test performance in the classification, localization, and quantitation tasks have not yet been developed. Efficacy-M (management efficacy) is a measure of the extent to which a procedure influences patient management appropriately. Efficacy O (outcome efficacy) is a measure of the success of therapeutic procedures. Some publications illustrating these points are presented. Costs associated with nuclear medicine procedures include money, time, discomfort, possible drug reactions, radiation dose, and the hypothetical risk of radiation-associated cancer. The public's perception of these latter risks, or costs, is much higher than our knowledge would justify. Decision trees are useful for laying out all possible strategies, outcomes, costs, and benefits, and estimating the cost effectiveness of each strategy. Some articles estimating cost-effectiveness in nuclear medicine are reviewed, although few articles in the literature make any detailed use of decision analysis. Much work remains to be done in forming a coherent, consistent procedure for assessing cost-effectiveness in nuclear medicine. PMID- 8469999 TI - Anterior correction of idiopathic scoliosis using TSRH instrumentation. AB - The first 14 consecutive patients with idiopathic lumbar scoliosis treated by anterior Texas Scottish Rite Hospital (TSRH) instrumentation are reported. Frontal curve correction averaged 76%, with a 5 degrees (9%) loss of correction in the follow-up period, which averaged 17.6 months (range, 12-29). Spinal balance was improved an average of 1.8 cm toward the center sacral line, and apical vertebral rotation was corrected an average of 49%. Instrumentational kyphosis was minimal, with total L1-S1 lordosis decreasing an average of 1 degree, and no measured compensatory hyperlordosis caudal to the instrumented segment. One hundred percent of disc spaces were radiographically fused by 8 months. There were no neurologic, septic, or implant complications. The contoured solid rod used in this construct provides the same frontal and rotatory correction as previous systems, and minimizes instrumentational kyphosis. Fusion occurs rapidly and reliably because of the stiffness of the construct, which also may eliminate the need for postoperative immobilization. PMID- 8470000 TI - Anterior spinal fusion with Zielke instrumentation for idiopathic scoliosis. A frontal and sagittal curve analysis in 36 patients. AB - The authors have reviewed the records of 36 patients with idiopathic scoliosis who underwent a single-stage anterior spinal fusion with Zielke instrumentation to determine if any adverse frontal or secondary sagittal deformities or changes in balance resulted from the surgery. Spontaneous correction of uninstrumented thoracic curves was noted in five patients with double-major curves, and frontal balance was maintained or improved after operation in all but four patients. Kyphosis was increased in the instrumented segments in all patients. In the uninstrumented segments, however, thoracic kyphosis and lumbar lordosis were decreased in all but five patients after operation, whereas overall sagittal balance was not adversely affected by the surgery in any patient. PMID- 8470001 TI - Cotrel-Dubousset instrumentation. Results in 52 patients. AB - Fifty-two posterior spinal fusions were performed for pediatric idiopathic, congenital, and neuromuscular scoliotic curves. Cotrel-Dubousset instrumentation was used in all patients. Nine had prior anterior spinal releases and fusions. The patterns were mixed, with a predominance of right thoracic curvatures. The average preoperative curve measured 60.6 degrees, with correction to 29. Seven patients required revision surgery, and 17 wore orthoses after operation. There were 17 complications in this group, including hook pullout, prominent hardware, infection, pseudarthrosis, and two cases of broken Cotrel-Dubousset instrumentation rods. Fatigue failure of this instrumentation, secondary to pseudarthrosis, has not been reported previously, and these two cases are presented in detail. The operative morbidity and difficulty were increased in the larger idiopathic curves and in neuromuscular and congenital scoliosis. Cotrel Dubousset instrumentation is an overall excellent tool for the multiplanar correction of scoliosis and is amenable to revision surgery. PMID- 8470002 TI - Long-term results of Boston brace treatment on vertebral rotation in idiopathic scoliosis. AB - The long-term effect of Boston brace treatment was investigated by computed tomography measurements before treatment, after bracing, and at mean follow-up at 8.5 years in 25 patients with idiopathic scoliosis. At follow-up, the pretreatment Cobb angle, the vertebral rotation, the rib hump, and the translation of the apical vertebra were not significantly changed. The sagittal diameter of the thoracic cage was significantly decreased at follow-up. The current study demonstrates that the Boston brace does not improve, but prevents progression of vertebral rotation, translation, rib hump, and Cobb angle in idiopathic scoliosis. The reduced sagittal diameter is noteworthy and may be of importance for cosmesis and pulmonary function. PMID- 8470003 TI - External electrical stimulation and bracing for treatment of spondylolysis. A case report. AB - Evidence indicates that osseous healing of acute spondylolysis can occur without surgery, although no existing data supports a particular regimen that optimizes healing. This article presents a case study of a 17-year-old athletic male student who presented with acute spondylolysis and who was treated with intermittent bracing and daily external electric stimulation. The patient was treated with a thoracic lumbar sacral orthosis to which an external bone growth stimulator was added. Computer tomography scans performed throughout the treatment process and described in this report illustrate the progressive healing of the right and left pars fractures. PMID- 8470004 TI - Modified repair of a defect in spondylolysis or minimal spondylolisthesis by pedicle screw, segmental wire fixation, and bone grafting. AB - A surgical technique for treatment of spondylolysis or minimal isthmic spondylolisthesis is described. The authors based their treatment on the Scott technique, which involves placing an 18-gauge stainless steel wire around the transverse process bilaterally and then tightening the wires to each other inferiorly to the posterior spinal process. The modified technique consists of a tension band wire around the posterior spinous process and a 4.5 mm AO cortical screw in the pedicle. A case study of a 20-year old female athletic student is presented to illustrate the effectiveness of the modified technique. The authors believe that this technique offers the advantages of maintaining all motion segments and avoiding the risks of damaging the exciting nerve root just beneath the transverse process. PMID- 8470005 TI - Translaminar facet screw fixation in lumbar spine fusion. AB - This study evaluates the clinical result and fusion rate in 61 patients who underwent posterolateral spine fusions augmented with translaminar facet screw fixation at an average of 24 months after surgery. Sixty patients (98.4%) were judged to have a solid fusion by radiographic examination at an average of 5 months. Fifty-seven patients (93.4%) rated the result of their surgery as good to excellent; four patients (6.6%) rated their result as unsatisfactory. There were no patients with nerve root injury or other neurologic deficit. The 98.4% fusion rate compares favorably with other methods. The results of this study support the continued use of translaminar facet screw fixation to augment posterolateral fusion in the lumbar spine. PMID- 8470006 TI - Posterior instrumentation and fusion for unstable fractures and fracture dislocations of the thoracic and lumbar spine. A comparative study of three fixation devices in 70 patients. AB - Acute unstable thoracic and lumbar spine fractures were treated with either Harrington rods and hooks, Luque rods with sublaminar wires, or A-O dynamic compression plates with pedicle screws. The results demonstrated failure of all three techniques to maintain the sagittal plane correction at 12 months' follow up. Furthermore, in lumbar fractures, Harrington rods did not restore or maintain sagittal plane alignment as well as Luque rods or pedicle screws and plates. Lastly, the pedicle screw fixation system required a shorter segment fusion. PMID- 8470007 TI - Anterior transpedicular fixation of the lower thoracic and lumbar spine. Experimental verification using a new direction finder. AB - Currently, no anterior spinal implant provides a strong bone-screw interface because of the cancellous characteristics of the vertebral body. A more secure anchorage could be obtained by anterior transpedicular screw fixation. Four hundred transpedicular screws located between T7 and L5 were placed using the newly developed direction finder. Measurements were obtained directly from radiographs of the cadaveric specimens. In 10 cases (2.5%), the screws crossed the medial pedicle border, but never by more than 1.4 mm. A lateral protrusion was noted in another 41 screws (10%), with no protrusion greater than 2.2 mm. Encroachments beyond the superior or inferior border were not observed. The mean angle of the screws at each level measured between 7 and 19 in the transverse plane and between 2 and 4.5 in the sagittal plane. This technique should be reserved for vertebrae without significant arthritic changes. The rare screw with minimal infraction through the medial or lateral pedicle wall should not cause any vascular or neural compromise. The anterior transpedicular screw technique appeared relatively safe (88%) and encouraged the development of the new plate system for anterior spinal stabilization. PMID- 8470008 TI - Cotrel-Dubousset rods in surgical stabilization of spinal fractures. AB - Cotrel-Dubousset instrumentation (CDI) was used to stabilize thoracolumbar fractures in 48 consecutive patients at the Lucerne Spinal Center. The results of these patients were reviewed with respect to completion of healing, change in neurologic status, medical or hardware complications, and follow-up radiographic parameters. Twenty patients were braced and 28 were not braced after operation, depending on certain criteria. Two elderly patients died at 1 and 6 months after their injury, of medical complications. One other patient was lost to follow-up after 6 months. Of the remaining 45 patients, all were evaluated at follow-up ranging from 12 to 47 months (mean, 21 months). Forty-two of the 45 patients (93%) developed a solid stable fusion with the initial procedure. Ten patients of 45 required additional surgical procedures for a complication rate of 22%, as follows: there were two early hardware failures requiring revision and one late failure that did not require revision. Five patients required late rod removal because of pain. One patient required late syrinx drainage without removal of hardware, and another adolescent patient required extension of her fusion because of late scoliosis development below the injury site. There were no infections or neurologic complications. Cotrel-Dubousset instrumentation rods have been found to be an excellent device for thoracolumbar fracture stabilization. PMID- 8470009 TI - Residual intersegmental spinal mobility following limited pedicle fixation of thoracolumbar spine fractures with the fixateur interne. AB - The Fixateur Interne has been proposed for limited pedicle fixation of thoracolumbar spine fractures with the assumption that motion in the nontraumatized spinal segments could be maintained. To date, no data exist that both localize and quantitate spinal mobility about the fractured vertebra. Voluntary maximum lateral flexion and extension radiographs were obtained on patients with unstable thoracolumbar spine fractures at a minimum of 2 years after Fixateur Interne instrumentation (implant was removed after 1 year). Residual intersegmental motion was measured at levels adjacent to both the vertebra fracture and the fixation. Fifty-nine patients were reviewed, and the posterior vertebral body angle demonstrated a mean total sagittal motion of 2.98 degrees. Cephalad and caudal to the fractured vertebra, a mean of 1.34 degrees and 3.08 degrees, respectively, of residual motion was noted; cephalad and caudal to the previously instrumented segment a mean of 3.22 degrees and 6.88 degrees, respectively, was measured. The authors conclude that residual mobility is most evident at the caudal end of the instrumented segment, removed from the fractured vertebra. The level with end plate disruption becomes essentially ankylosed, with or without a fusion. PMID- 8470010 TI - Review of Harrington rod treatment of spinal trauma. AB - Harrington rod treatment for spinal trauma has become the gold standard against which other treatment modalities are judged. A review of the results of Harrington rod treatment is essential to establish a baseline level of efficiency in terms of rehabilitation time, correction of deformity, canal decompression, motion segment loss, and device-related complications. With economic concerns becoming more important in medical treatment, the value of newer techniques must be clearly superior to established methods. Harrington rod-augmented spine fusion is reliable and cost-effective in the thoracic and thoracolumbar spine. The risks of rod failure and late complications related to lost motion segments in the lumbar spine make pedicle screw systems a better option in this region. PMID- 8470011 TI - Late infection of spinal instrumentation by hematogenous seeding. AB - Six cases of late spinal infection following instrumentation are described. In all cases, there was a delay of at least 10 months between surgery and the clinical development of sepsis. In 5 of the 6 cases, a distant focus of infection could be identified. Two patients had active intravenous drug usage, two patients were paraplegic with neurogenic bladders, and one patient had an episode of pyelonephritis secondary to renal calculi two months prior to presentation. In no instance was there any preceding breakdown of overlying skin. This previously unreported phenomenon is an extremely rare but major complication of spinal surgery. PMID- 8470012 TI - The selection of wires for sublaminar fixation. AB - The authors report a comparative biomechanical study of the suitability of four types of stainless steel wire for sublaminar fixation. Tensile and fatigue tests were performed on wires in the configuration used at surgery. They conclude that annealed 18-gauge (1.2 mm) wire should be used at each end of a scoliosis fusion, at the upper end of a lumbar fusion, and throughout for thoracolumbar fractures. Cold-worked 20-gauge (0.87 mm) wire may be used in all other situations, but the use of annealed 20-gauge wire should be restricted to the cervical spine. The authors emphasize the importance of achieving the correct balance between wire stiffness and flexibility, of care in the handling of wires, and of proper technique in achieving secure fixation. PMID- 8470013 TI - Kinematics of the lumbar spine following pedicle screw plate fixation. AB - This investigation was conducted to determine the kinematic response of the lumbar spine instrumented with transpedicular screws and plates. Seven unembalmed human cadaveric lumbar spines were used. Retroreflective targets were inserted into the bony landmarks of each vertebral body, facet column, and spinous process. The specimen was quasistatically loaded until failure (initial cycle) using an electrohydraulic testing device at a rate of 2.5 mm/sec. After radiography, the specimen was again loaded (injury cycle) to the failure compression determined in the previous cycle. Transpedicular screws then were inserted bilaterally at one level proximal and distal to injury. The stabilized cycle of loading was conducted using the procedure adopted in the injury cycle. Comparative analysis of the localized kinematic data between the stabilized and injured columns indicated a reduction in motion between fixated levels, increasing the rigidity of the column. At levels proximal and distal to fixation, however, motion increased, indicating added flexibility. These alterations in the motion, observed during single-cycle loading, may be further accentuated in vivo, leading to hypermobility and degeneration of the spine. PMID- 8470014 TI - Anterior spinal fixators. A biomechanical in vitro study. AB - In vitro calf spine testing was performed in flexion, rotation, and axial load, using a vertebral body corpectomy and anterior iliac crest bone grafting model. Anterior spinal fixation devices then were sequentially tested, and axial stiffness, torsional stiffness, and flexural strain determined. The constructs tested were the Contoured Anterior Spinal Plate (CASP), the Kaneda device, the Kostuik-Harrington device (KH), and the Texas Scottish Rite Hospital (TSRH) vertebral body screw construct. In torsion, the Kaneda device returned spinal stability to that of the intact spine. The Kostuik-Harrington device was unstable in torsion. In axial loading and flexion, the Kaneda device and the TSRH construct proved the most stiff, with the KH and CASP systems significantly lower in stiffness. The authors believe that the Kaneda device and the TSRH vertebral body screw construct are effective in restoring acute stability to the lumbar spine after corpectomy. PMID- 8470015 TI - Somatosensory evoked potential monitoring during Cotrel-Dubousset instrumentation. Report of a case. AB - Somatosensory evoked potentials produced by electrical stimulation of the posterior tibial nerve were recorded from surface electrodes at the scalp and cervical spine of a patient with scoliosis undergoing posterior spinal fusion with Cotrel-Dubousset instrumentation. During spinal derotation when hypotension and anemia were also present, the cortical and subcortical somatosensory evoked potentials disappeared. During a wake-up test, the patient demonstrated weakness of the left lower extremity, and derotation was stopped. The patient was given pharmacologic hypertensive agents and blood transfusions to increase blood pressure. Forty minutes later, somatosensory evoked potentials returned and a second wake-up test demonstrated normal function in both lower extremities. This report demonstrates the accuracy and usefulness of somatosensory evoked potential monitoring during spinal fusion with Cotrel-Dubousset instrumentation. To the authors knowledge, this is the first report demonstrating a correlation between abnormal SEP responses and intraoperative neurologic deficit during the derotation maneuver with Cotrel-Dubousset instrumentation and corrected by transfusion and restoration of normotension. PMID- 8470016 TI - Esophageal penetration by an anterior cervical fixation device. A case report. AB - Esophageal complications following anterior cervical fusion procedures have been reported in the literature as rare complications of such surgery. The complications associated with esophageal penetration have ranged from minor complications to mediastinitis and death. The following case report is of a rare complication of penetration of the esophagus by an anterior cervical fixation device that resulted in a benign post-operative course. PMID- 8470017 TI - [Project for establishing medico-pharmaceutical uniformity throughout the Republic. 1879]. PMID- 8470018 TI - [Effectiveness of a carbamate insecticide as a household low-volume spray for malaria control]. AB - A comparative regional-scale evaluation of the epidemiological impact of low volume (LV) spray of bendiocarb and the conventional spray of DDT against malaria in an endemic area of northern Chiapas was carried out. Three Anopheline species were found: Anopheles pseudopunctipennis, An. albinanus and An. argyritarsis. The most prevalent was An. pseudopunctipennis, a species we suspect may be involved in the transmission of most malaria cases. This species showed high levels of resistance to DDT. However, this insecticide had a long residual effect in wall bioassays, with mortalities > or = 95 per cent for up to 21 weeks in wood, sticks and plaster. Susceptibility to bendiocarb was total, and mortality to LV bendiocarb was > or = 75 per cent for up to 16 weeks in wood, sticks and straw. Very low numbers of mosquitoes were found throughout the evaluation, although malaria transmission continued in control villages (sprayed with DDT), as well as treated villages (sprayed with LV bendiocarb). No plasmodium infected mosquitoes were found, perhaps due to a very small sample size. The LV spray methodology was found to be 1.7 times more effective than conventional spraying in reducing malaria incidence. A net reduction of 1.6 times in insecticide application time was also found, which would allow spraying at the right time, especially when urgent control measures have to be applied, such as in malaria outbreaks. Finally, the new methodology costs 2.2 times more than the conventional ddt spraying, but if the potential of using spray workers in other activities is considered, costs would be comparable to those of DDT spraying. PMID- 8470019 TI - [Perspectives on cholera vaccines]. AB - Perspectives of cholera vaccines with emphasis in their possible usage in Latin American countries are discussed. Microbiology, antigenicity, relevant aspects of traditional serology, protective immune responses and epidemiological data up to December, 1991, are presented. Indications of parenteral vaccines are discussed. Finally, perspectives of usage of cholera vaccines in Latin America are analyzed. PMID- 8470020 TI - [Hemorrhagic fever and the dengue shock syndrome]. AB - Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) are the severe and/or fatal clinical manifestations of dengue fever. Epidemics of DHF/DSS occur mainly in the southeast Asian countries where children are seriously affected and high case-fatality ratio is annually reported. Recently significant epidemics of DHF/DSS have been reported in Cuba, Venezuela and Brazil, which means that reinforcements of the epidemiological surveillance in the countries of the American region that show high virus transmission, are urgently needed. The main purpose of the present article is to review relevant information regarding the clinical manifestations, pathology, diagnostic procedures, treatment of cases, pathophysiologic mechanisms and some data related with specific DHF/DSS epidemics. PMID- 8470021 TI - [Detection of antibodies against Trypanosoma cruzi in blood donors]. AB - American trypanosomiasis is an endemic disease in Mexico. Blood transfusion has been recognized as the second main mechanism of transmission in South American countries. There is no definitive information available for Mexico. We obtained the prevalence of IgG antibodies against Trypanosoma cruzi among 1076 blood donors at the Instituto Nacional de Cardiologia "Ignacio Chavez" in Mexico City. We used an antigen freshly prepared from local isolates, and the complete and soluble antigen preparations were analyzed with the Western blot technique using sera previously characterized as reactive. Blood donors' antibodies were studied with DOT-ELISA and Western blot. All donors were asked in regard to place of birth, and blood samples were serologically tested as usual in transfusion practice. The presence of IgG antibodies to T. cruzi, confirmed with a high specificity test, showed a prevalence of 0.28 per cent. Screening for antibodies to T. cruzi; should be included in the evaluation of blood donors in Mexico. PMID- 8470022 TI - [Reproductive risk factors and uterine cervix cancer in Mexico City]. AB - An epidemiological case control study nested in the Early Cancer Detection program of the Health Ministry in Mexico City was carried out to evaluate the principal reproductive risk factors associated with uterine cervix cancer. Information from 12,741 gynecological cytologies reported to the National Cancer Registry, during the period between January 2 to March 31, 1987 was studied. In this population group the most important reproductive risk factors associated with uterine cervix cancer were: multiple births (seven or more births, OR = 3.24, IC 95% = 2.20-4.76), initiation of active sex life before 14 years (OR = 1.53, 95% IC = 1.13-2.08) and late menarche (in the group with menarche after 17 year of ages OR = 3.22, 95% IC = 1.06-9.77). In relation to the Early Cancer Detection program, an important number of women made use of the program when they showed symptoms. The prevalence among women who had at least one symptom was 43.09 per cent. Women with a tumor at the cervical level at the time of the cytology were 7.76 times more likely to have of uterine cervix cancer (95% IC = 4.84-13.15). Symptoms such as dysfunctional bleeding (OR 2.79, IC 95% = 1.90 4.12), metrorrhagia (OR 2.66, 95% IC 1.83-3.86) and bloody leukorrhea (OR 2.64, 95% IC 2.05-3.38) can be relevant findings in women at high risk. The attributable fraction of higher exposure in the presence of gynecological signs and symptoms is the cervical tumor, with 87.46 per cent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470023 TI - [Midwives' perception of reproductive risk factors]. AB - Midwives in rural areas of the State of Morelos are one of the most important resources used by rural women for health care of pregnancy, delivery and the puerperium. This work was aimed at identifying midwives perceptions of pregnant women's risk factors, in order to include this knowledge in reproductive health programs which articulate institutional and traditional health systems. We applied a questionnaire to all midwives in the Municipalities of Ocuituco, yecapixtla and Zacualpan, Morelos (n = 35). Four key informants were selected and interviewed. These instruments enabled us to measure variability in perception of risk factors. Knowledge of risk factors is defective among midwives. Previous training made a big difference. Sixty three per cent of midwives who attended training courses are better qualified from an academic medicine point of view. Only 28.7 per cent of non-trained midwives (43% for both groups), indicating that sociocultural aspects prevail over technical training in midwives perceptions of reproductive risk factors. PMID- 8470024 TI - [Training of epidemiology personnel in Cuba]. AB - We describe the academic characteristics of the Master of Epidemiology Program taught at the Instituto de Medicina Tropical "Pedro Kouri", in La Habana, Cuba. We provide a description of the structure of the course along with its didactical principles, the main objectives of the different academic modules and the number and background of graduates from seven Classes. We also discuss potential work areas for graduates and short-term perspectives for their continuing education. PMID- 8470025 TI - [Priorities of progress in evaluating and monitoring quality of care]. AB - This paper discusses the following priorities: redefining and widening the scope of assessment, redefining assessment methods, redesigning and evaluating quality assurance systems, promoting consumer participation, professionalizing quality assurance, and creating a supportive culture. The article proposes empirical assessment of quality assurance methods as the highest priority. It concludes with the idea that seeking quality is the ethical dimension of professional life. Therefore, all reasonable efforts towards monitoring quality will be successful. Without this, the cleverest monitoring systems will fact. PMID- 8470026 TI - [3D reconstruction of CT data sets. A methodologic comparison]. PMID- 8470027 TI - [The clinical application of MR angiography in aortic diseases]. PMID- 8470028 TI - [The place of MR venography in the diagnosis of deep leg and lower limb venous thrombosis]. PMID- 8470029 TI - [Color Doppler sonography of superficially situated malignant tumors]. PMID- 8470030 TI - [Epidemiological data on chronic myeloid leukemia in Asturias, 1972-1986]. AB - PURPOSE: To evaluate the incidence of CML in Asturias during the period 1972 1986, studying the variations in relation to age, sex and geographical zone. MATERIAL AND METHODS: Information relating to the date of diagnosis, name, age, sex and home address of the 108 cases (65 men and 43 women) diagnosed CML during the period 1972-1986 according to conventional criteria was collected from the hospital records of the region. For the calculations, SADEI demographic data were taken as a reference, comparing the incidence between sexes and geographical zones by means of the CHI2. RESULTS: A rate of incidence of 0.64/100,000 inhabitants/year was obtained, this being 0.8 in men and 0.5 in women (p < 0.05). The rate of incidence increased progressively with age until the 45-59 age group when it was maximum. There were no differences between the three main centres of population Gijon (0.53), Oviedo (0.55) and Aviles (0.69) nor the latter with the rest of the zones in Asturias; nor was three either any difference between coastal towns (0.56) and those of the interior (0.71) (p = NS). CONCLUSIONS: Limited incidence of CML in Asturias without significant differences in its geographical distribution within the region. The incidence, which was higher among males, increased progressively with age until reaching maximum importance in the 45-59 age group. PMID- 8470031 TI - [Allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia]. AB - PURPOSE: Long disease-free survival can be achieved with chemotherapy in over 50% of children with acute lymphoblastic leukaemia (ALL). However, those children suffering relapse or presenting with poor-risk features at diagnosis have scarce possibility of doing well with conventional chemotherapy. Bone marrow transplantation (BMT) is a good choice in such cases. MATERIAL AND METHODS: Between July 1985 and January 1992, twenty-four children with ALL underwent BMT in the Service of Pediatrics of the Hospital Ramon y Cajal. In seven patient with poor-risk criteria at diagnosis BMT was performed in the first complete remission (CR) and in seventeen cases it was performed after the second CR. The conditioning for transplantation consisted of cyclophosphamide plus total body irradiation in 21 patients and cyclophosphamide plus busulphan in 3 others. RESULTS: Fifteen patients persist in CR with post-transplant follow-up of 3 to 73 months (median, 31 months). Five patients died due to complications of the transplantation techniques, and four others died upon leukaemic relapse. The probability of disease-free survival for all cases is 61%, a plateau being reached at 13 months (83% and 52% for BMT in first or second CR, respectively). CONCLUSIONS: These findings confirm the efficacy of BMT in the treatment of children with ALL in second CR, or in first CR when there are very poor risk criteria at diagnosis. PMID- 8470032 TI - [Comparative study of 1st generation versus 2d generation (CAVPE) combinations in intermediate and high-grade lymphomas]. AB - PURPOSE: To compare four first generation chemotherapy regimes (FGR) used by GATLA in low and intermediate grade lymphomas. Versus a second generation regimen called CAVPE. PATIENTS AND METHODS: A group of 205 patients treated with FGR (79 with BACOP, 89 with COPP, 19 with CHOP, and 18 with CNOP), and 244 others treated with the combination of cyclophosphamide, doxorubicin, vincristine, prednisone and etoposide (CAVPE) were included. Two randomized phase III multicentric studies, COPP vs BACOPP and CHOP vs CNOP, as a whole group, were compared with the second generation scheme, CAVPE. All the patients with FGR received 6 monthly treatment courses, and the CAVPE patients were given 8 monthly courses. RESULTS: The median age was 55 years (18-85) for the FGR group and 51 years (15-79) for the CAVPE group. The stage distribution for both FGR and CAVPE groups was, respectively, as follows: II: 38 and 55 cases; III 80 and 84 cases; IV: 87 and 105 cases. No significant differences were found between both groups when comparing other characteristics of the patients, namely, sex, symptoms, mediastinal, abdominal or extranodal involvement, liver, spleen or bone-marrow infiltration, and bulky tumoural mass. The percentage of complete remission (CR) was 52% (107/205) in the patients treated with FGR, and 67% (163/244) in the CAVPE group (p < 0.001). The estimated probability of sustained first CR at 72 months was 38% for the FGR group and 54% for the CAVPE group (p = 0.0167), whereas 17% and 36%, respectively, of the evaluable patients were alive and well, with no signs of disease progression (p = 0.000). The 72-month survival was estimated in 32% and 51%, respectively, for each group (p = 0.0004). CONCLUSIONS: 1. CAVPE seems to offer better responses and disease-free survival in this non selected group of low and intermediate lymphoma patients. 2. The better results in terms of CR and lower incidence of relapses attained with CAVPE with regard to FGR are probably related with a number of facts, such as the use of more aggressive drugs, higher doses, a better drug combination rationale, the inclusion of new drugs, such as etoposide, or a selection of the patients. PMID- 8470033 TI - [Treatment of acute lymphoid leukemia (ALL) in the child]. AB - PURPOSE: To analyse the results of the therapy administered to children with ALL in Cuba. PATIENTS AND METHODS: Four-hundred and twenty-five children (aged below 15 years), diagnosed of ALL in 8 different Cuban hospitals between 1973 and 1991, were evaluated. Five different therapeutic regimes were used: three "classic" GLATHEM protocols in the first period (1973-1981) and two intensive BFM-like protocols in the second period (1982-1991). The Kaplan-Meier method was applied for survival analysis, and the differences were evaluated by the log-rank and Mantel-Cox methods. RESULTS: Two-hundred and sixty-five patients were included in the first period, 81 with low-risk disease, 133 with standard risk and 51 with poor-risk leukaemia. The second period comprised 160 cases, 50 of low-risk, 83 with standard risk and 27 with poor-risk leukaemia. The disease-free survival probability at 60 months was 35% for the first group and 55% for the second (p < 0.0001). The 60-month survival (SV) as a whole was 45% for the "classic" treatments and 60% for the BFM-like protocols (p < 0.01). The disease-free survival (DFS) probability for each prognostic group was as follows: 50% for low risk, 43% for standard risk, and 25% for poor-risk (p < 0.001) and the probability of survival as a whole was, respectively, 65%, 49% and 28% (p < 0.001). as for this compilation, 172 patients were out of any treatment for periods ranging between 14 and 168 months. CONCLUSIONS: 1) The percentage of remissions was similar for both groups of treatments. 2) The results attained with BFM-like protocols were better than those of the "classic" therapy with regard to the SV and DFS differences. 3) Significant differences can be appreciated between good- and poor-prognosis groups for both types of treatment. PMID- 8470034 TI - [Salvage treatments in non-Hodgkin's lymphoma. I]. PMID- 8470035 TI - [Evolution of CD4 and CD8 lymphocyte subsets in HIV seronegative and seropositive hemophiliacs]. AB - PURPOSE: To asses the evolution over time of the CD4, CD8 and total lymphocyte counts in both HIV seronegative and HIV seropositive haemophiliacs. PATIENTS AND METHODS: A total of 124 haemophilic patients (77 HIV seropositive and 47 HIV seronegative) regularly controlled at our Hospital were studied. All patients have had several (range 2-15) CD4 and CD8 lymphocyte counts, with a minimum interval of 2 or more years between the first count and the last one (median 7.7 years). A linear regression analysis of the serial cell counts against the time was made and the corresponding slopes were estimated for each patient and expressed as a percentage of the initial values (standardized slopes). RESULTS: In HIV seronegative patients the number of CD4, CD8 and total lymphocytes decreased (p < 0.05), but the decrease of the CD4/CD8 ratio was not statistically significant. The decline of the CD4 cells showed a trend to remain above 500 cells/microL. HIV seropositive hemophiliacs had also a substantial decline of lymphocyte counts (p < 0.0001), but essentially due to changes of the CD4 cells, which declined with a nearly constant rate during the follow-up (median values decreased from 793/microL to 324/microL). CD8 cell counts diminished in lower grade than the CD4 cells counts, and consequently the percentage of the total lymphocyte number increased from 42% to 55%. The CD4/CD8 ratio decreased with a standardized slope of -5.7% per year. At the initial evaluation the seropositive patients had CD4 cell counts and CD4/CD8 ratios lower than seronegative ones, but CD8 cell counts were higher in the first group. Total lymphocyte counts were not statistically different at this first evaluation between infected and non infected patients. At the final evaluation, differences on CD4 cell counts and CD4/CD8 ratio increased, and lymphocyte counts were significantly lower in the HIV-seropositive haemophiliacs. However, the final absolute counts of CD8 cells were not dissimilar in the two groups of patients. The median standardized slopes of the total lymphocyte counts, CD4 cell counts, and CD4/CD8 ratios were significantly more negative for the HIV-infected patients (-5.7%, -9.4 and -5.7%, respectively) than were these for the non-infected ones (-2.0%, -3.2% and -2.5%, respectively). CONCLUSIONS: Lymphocyte counts, mainly the CD4 cell counts, decline in treated haemophiliacs independently of their HIV status. In the HIV seronegative patients the CD4 cell counts generally stabilize above 500 cells/microL. However, in the seropositive haemophiliacs these counts show a continuous fall, with a median rate of 9% of the initial value per year. PMID- 8470036 TI - [Hemophagocytic syndrome associated with histoplasmosis in the acquired immunodeficiency syndrome: description of 3 cases and review of the literature]. AB - Three cases of haemophagocytic syndrome (HPS) due to histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS) are described. At admission all had pancytopenia and the bone marrow aspirate showed typical haemophagocytosis and the presence of intracellular inclusions compatible with Histoplasma capsulatum. One patient had also cerebral toxoplasmosis. One patient died shortly after admission from multiple organ failure. Two patients survived, one treated with fluconazole and another with amphotericin-B with good response and progressive increase in their blood cell counts. We suggest that haemophagocytic syndrome due to disseminated histoplasmosis should be included in the causes of pancytopenia in patients with AIDS. Bone marrow aspirate is the best method for diagnosis. PMID- 8470037 TI - [3 families with a congenital factor X deficiency, one of them with an associated factor XII deficiency]. AB - Factor X deficiency constitutes one of the most uncommon congenital bleeding disorders. Here we report three families with Factor X deficiency, one of them with an associated deficit of Factor XII. Family I presented Red variant deficiency (low functional and antigenic activity, the latter in higher levels than the former). In Family II functional activity was low but antigenic one was normal (Prower defect). Besides, an heterozygous deficiency of factor XII was diagnosed. Although genetic analysis supports the hypothesis of combined deficiency, the study was possible in only two generations of the propositus, so a multiple familial deficiency could not be discarded. Finally, Family III suffered from a "classic" or Mr. Stuart deficiency (low levels in functional and immunological assays). Besides, crossed immunoelectrophoresis showed a grossly pathological pattern. PMID- 8470038 TI - [Reference values in hematology]. PMID- 8470039 TI - [Richter syndrome with exclusively cutaneous involvement]. PMID- 8470040 TI - A little help from my friends. PMID- 8470041 TI - Proposed resolutions for the 1993 TNA HOD. On uniform data reporting about needle sticks among health care workers in Texas. PMID- 8470042 TI - AIDS Q & A. Antiretroviral drugs. Part 2. PMID- 8470043 TI - Paris I dysfibrinogenemia: a point mutation in intron 8 results in insertion of a 15 amino acid sequence in the fibrinogen gamma-chain. AB - Paris I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal gamma-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the gamma-chain region of the Paris I subject's genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A-->G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I gamma-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature gamma Paris I chain mRNA, and encodes a 15 amino acid insert after gamma 350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I gamma chain mRNA also results after translation into a substitution of S for G at position gamma 351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the gamma Paris I chain. We conclude that the insertion of this amino acid sequence leads to a conformationally-altered, and dysfunctional gamma-chain in Paris I fibrinogen. PMID- 8470044 TI - Heparin-releasable and platelet pools of tissue factor pathway inhibitor in rabbits. AB - Earlier studies from this laboratory have established that tissue factor pathway inhibitor (TFPI) functions as a natural anticoagulant protecting rabbits from intravascular coagulation triggered by the exposure of blood to small amounts of tissue factor. In addition to the TFPI circulating in plasma, humans have been shown to have heparin-releasable and platelet pools of TFPI. In order better to extrapolate from studies carried out in rabbits to an understanding of human hemostasis, we have examined the presence and extent of heparin-releasable and platelet pools of TFPI in rabbits. We find that in the rabbit the heparin releasable pool of TFPI activity, as measured in a capacity assay, may be smaller relative to the plasma pool than in humans; that the platelet pool of TFPI activity is comparable to that of humans; and that rabbit TFPI, unlike human TFPI, has the same apparent molecular mass in all vascular pools. These studies extend our understanding of the properties of TFPI in rabbits and the appropriateness of using the rabbit for studies of TFPI relevant to human hemostasis. PMID- 8470045 TI - The effects of heparin and annexin V on fibrin accretion after injury in the jugular veins of rabbits. AB - We compared the relative abilities of unfractionated heparin and annexin V to prevent fibrin accretion onto injured jugular veins in vivo. Heparin was used to accelerate the inhibition of thrombin by antithrombin III, and annexin V was used to inhibit the assembly of the prothrombinase complex on phospholipid surfaces, thereby blocking thrombin generation. Rabbit jugular veins were isolated in situ, a 2 cm segment was injured by perfusing it with air, and then blood flow was re established. Five minutes later, each rabbit was injected with heparin (20 U/kg) or annexin V (0.3 mg/kg) and then with 125I-fibrinogen. The amount of 125I-fibrin accumulation onto each injured vessel wall segment was measured 4 h later. Each injured vessel was completely de-endothelialized as a result of the air perfusion as demonstrated by electron microscopy. 125I-fibrin accretion onto the injured jugular veins was enhanced 2.4-fold as compared to the uninjured veins in sham operated animals. Heparin treatment did not reduce fibrin accretion, whereas, annexin V treatment decreased fibrin accretion by 60%, p < 0.05. This latter effect was achieved without sustained circulating anticoagulation. Additional experiments confirmed that the inhibitory effect of annexin V on fibrin accretion was associated with a surface specific effect, since more annexin V bound to the injured jugular vein segments as compared to the non-injured jugular veins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470046 TI - An antithrombin III assay based on factor Xa inhibition provides a more reliable test to identify congenital antithrombin III deficiency than an assay based on thrombin inhibition. AB - OBJECTIVES: To determine whether functional antithrombin III (AT-III) levels measured by a factor Xa inhibition (AT-III-Xa) assay identifies AT-III deficient individuals more reliably than functional AT-III levels measured by a thrombin inhibition (AT-III-IIa) assay. STUDY DESIGN: Cross-sectional study. PATIENT POPULATION: Sixty-seven members of a large family with type 2 AT-III deficiency. INTERVENTION: DNA analysis was used as the reference diagnostic standard for AT III status and subjects were classified as AT-III deficient or non deficient according to these results. Functional AT-III levels were measured in all subjects using: 1) a chromogenic substrate for thrombin and added human thrombin (AT-III-IIa), and 2) a chromogenic substrate for factor Xa and added bovine factor Xa (AT-III-Xa). Functional heparin cofactor II (HC-II) levels were measured using a commercially available kit. The proportions of 125I-alpha thrombin complexed to AT-III and HC-II were measured by polyacrylamide gel electrophoresis and autoradiography. RESULTS: Thirty-one (46%) individuals were classified as AT-III deficient and 36 (54%) as AT-III non deficient. AT-III-Xa assay measured a significantly lower mean AT-III value and a narrower range for individuals classified as AT-III deficient than the AT-III-IIa assay. Using the AT-III-IIa assay, six subjects had borderline AT-III levels compared to none with the AT-III-Xa assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470047 TI - A method to determine the optimal intensity of oral anticoagulant therapy. AB - Oral anticoagulant therapy has been shown to be effective for several indications. The optimal intensity of anticoagulation for each indication, however, is largely unknown. To determine this optimal intensity, randomised clinical trials are conducted in which two target levels of anticoagulation are compared. This approach is inefficient, since the choice of the target levels will be arbitrary. Moreover, the achieved intensity is not taken into account. We propose a method to determine the optimal achieved intensity of anticoagulation. This method can be applied within a clinical trial as an "efficacy-analysis", but also on data gathered in day-to-day patient care. In this method, INR-specific incidence rates of events, either thromboembolic or hemorrhagic, are calculated. The numerator of the incidence rate is based on data on the INR at the time of the event. The denominator consists of the person-time at each INR value, summed over all patients, and is calculated from all INR measurements of all patients during the follow-up interval. This INR-specific person-time is calculated with the assumption of a linear increase or decrease between two consecutive INR determinations. Since the incidence rates may be substratified on covariates, efficient assessment of the effects of other factors (e.g. age, sex, comedication) by multivariate regression analysis becomes possible. This method allows the determination of the optimal pharmacological effects of anticoagulation, which can form a rational starting point for choosing the target levels in subsequent clinical trials. PMID- 8470048 TI - Genetic basis and carrier detection of hemophilia B of Chinese origin. AB - We have characterized the genetic defects of 17 hemophilia B patients of Chinese origin by means of the polymerase chain reaction (PCR) and direct sequencing. The single-strand conformation polymorphism (SSCP) was used as an initial screening method to analyze the entire coding region and the flanking introns of each individual's factor IX gene. The abnormal exons were subsequently amplified and the nucleotide sequence determined. Of the 17 patients studied, 16 had single point mutations and one had a gross gene deletion of exons VII and VIII of factor IX. Among these 16 factor IX variants with point mutations 13 were missense and two were nonsense mutations. The remaining one had a nucleotide deleted, resulting in frame shifting at amino acid residue 97. A total of ten novel mutations, including the one with gross gene deletion, are reported in this study which have not been described previously. Five of the remaining seven variants were missense mutations with novel amino acids substituted for residues 127, 132, 180, 207, and 215, respectively. Mutations containing different amino acid residues at those positions have been reported. The last two are variants that have already been described to contain mutations at amino acid residues 333 and 365, respectively. To evaluate the efficiency of SSCP analysis in assessing the mutated exons and to further confirm our results we sequenced the entire exons of all 17 factor IX genes. The mutations detected by SSCP method were indeed the only mutation identified in each factor IX variant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470049 TI - Antithrombotic activity of SR 46349, a novel, potent and selective 5-HT2 receptor antagonist. AB - SR 46349 (trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3(2-fluorophe nyl) propen 1-yl] phenol, hemifumarate) is the first member of a newly-developed 5-HT2 antagonist series. SR 46349 potently inhibited serotonin-induced aggregation of rabbit and human platelets (IC50 = 1 and 3.9 nM respectively) but had no effect on the action of other platelet aggregating agents. SR 46349 was 118 and 25 times more potent than ketanserin against 5-HT+epinephrine-induced aggregation of rabbit and human platelets respectively. A single per os administration of SR 46349 (1 mg/kg) resulted in a strong inhibition of 5-HT+epinephrine-induced platelet aggregation in the rabbit as measured ex vivo (67% inhibition, 6 h after the administration). Intravenous or oral administration of SR 46346 inhibited in a dose-dependent manner venous thrombosis induced by ligature of the jugular vein of rabbits whose blood was made hypercoagulable by i.v. administration of tissue thromboplastin. The doses of SR 46349 which inhibited 50% of thrombus formation were 1.5 +/- 0.8 mg/kg and 17 +/- 0.5 mg/kg after i.v. or oral administration respectively. When given i.v. to rabbits, SR 46349 exhibited a dose-dependent antithrombotic effect in an arterio-venous shunt model. Significant increase of the bleeding time was observed after the i.v. administration of 5 mg/kg of SR 46349 (3-fold increase). In dogs, SR 46349 inhibited cyclic coronary artery blood flow variations, complete abolition of CFVs being achieved after the i.v. administration of 0.5 mg/kg. In conclusion, SR 46349 is a highly potent, selective antagonist of serotonin in vitro and is to be considered as a potent, orally active antithrombotic agent. PMID- 8470051 TI - Human platelets possess tyrosylprotein sulfotransferase (TPST) activity. AB - Tyrosine sulfation is a widespread modification of secreted proteins including several coagulation proteins synthesized in the liver. Since factor V, a tyrosine sulfated protein, is also synthesized in megakaryocytes, we determined whether platelets posses tyrosylprotein sulfotransferase (TPST) activity. Using the synthetic substrate EAY, substantial TPST activity (0.405 +/- 0.049 pmol EAY-SO4 formed min-1 mg-1) was detected in platelet homogenates. This activity could not be accounted for by contaminating leukocytes, erythrocytes or plasma. The Km of platelet TPST for EAY was 3.7 microM and Vmax 0.09 pmol/min. For the cofactor 3' phosphoadenosine 5' phosphosulfate (PAPS) the Km was 1.7 microM and Vmax 0.11 pmol/min. The PAPS analogue 3',5'-adenosine diphosphate inhibited platelet TPST with an IC50 of 15.4 microM. These findings suggest that tyrosine sulfation of factor V will occur in megakaryocytes. Platelets may be a useful source for further study of TPST. PMID- 8470050 TI - Potentiating effect of clopidogrel and SR 46349, a novel 5-HT2 antagonist, on streptokinase-induced thrombolysis in the rabbit. AB - Current thrombolytic strategies have a number of important shortcomings including resistance to recanalization and development of acute reocclusion. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by SR 46349, a novel 5-HT2 receptor antagonist, or clopidogrel, an analogue of ticlopidine. The activity of these compounds was evaluated by following the lysis of radiolabelled fibrin under a continuous infusion of streptokinase (4,000 IU kg-1 h-1 over 4 h). Streptokinase alone induced 42% thrombolysis when compared to saline. The i.v. co-administration of SR 46349 or clopidogrel (10 mg/kg) enhanced significantly streptokinase-induced thrombolysis. Thrombolysis measured by [125I]-fibrinogen lysis increased to 65 and 59% respectively. This efficacy was achieved without additional prolongation of the template bleeding time observed with streptokinase alone. Thus, the concomitant use of a 5-HT2 receptor antagonist or an anti-ADP agent during streptokinase therapy may facilitate clot lysis. PMID- 8470052 TI - Effect of the infusion of OKY-046, a thromboxane A2 synthase inhibitor, on urinary metabolites of prostacyclin and thromboxane A2 in healthy human subjects. AB - The influence of OKY-046, a selective thromboxane synthase inhibitor, on prostanoid formation in healthy human subjects was studied. Vehicle (5% glucose solution) or OKY-046 in 5% glucose solution at 15 micrograms kg-1 min-1 was intravenously administered to five male healthy volunteers for 6 h. Platelet aggregation and thromboxane B2 (TXB2) formation induced by collagen and arachidonic acid were suppressed by the infusion of OKY-046, while both were not affected by the infusion of vehicle. Urinary excretion of 11-dehydro-thromboxane B2, one of major urinary metabolites of thromboxane A2 (TXA2) was decreased by the infusion of OKY-046, while that of 2,3-dinor-6-keto-prostaglandin F1 alpha, one of major urinary metabolites of prostacyclin (PGI2) was increased. The present study demonstrated that the infusion of OKY-046 improved the balance of TXA2/PGI2 into antithrombotic state in healthy subjects. It was also suggested that endogenously produced (probably platelet-derived) endoperoxides could be redirected into prostacyclin in vivo. PMID- 8470053 TI - Trimucytin: a collagen-like aggregating inducer isolated from Trimeresurus mucrosquamatus snake venom. AB - Trimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytin- and collagen-induced platelet aggregation and ATP release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470054 TI - Neonatal vitamin K prophylaxis. Report of Scientific and Standardization Subcommittee on Perinatal Haemostasis. PMID- 8470055 TI - Intracellular transport-deficient mutants causing hereditary deficiencies of factors involved in coagulation and fibrinolysis. PMID- 8470056 TI - Immunonephelometric determination of the C4b-binding protein. AB - A fully mechanised immunonephelometric method for the rapid and specific determination of C4b-binding protein (C4b-BP) in citrated plasma is described. The method utilizes commercially available rabbit antiserum against human C4b-BP and a nephelometer analyser. A single determination can be performed within 6 min, requiring 80 microliters sample volume. The measuring range is about 10 to 200% of normal C4b-BP. Precision is characterized by intraassay coefficients of variation between 1.5% and 2.8%, and interassay coefficients of variation between 4.0% and 4.6% for the same C4b-BP concentrations. The nephelometry of C4b-BP was correlated with electroimmunodiffusion (Laurell technique; r = 0.863, y = 0.909x+7.091, n = 79). C4b-BP concentrations (143%, 96-223%; median and 2.5th 97.5th percentile) from 83 subjects with increased inflammation markers C reactive protein (> 10 mg/l), and fibrinogen (> 4.5 g/l) showing significantly higher C4b-BP concentrations compared to 151 obviously healthy subjects (97%, 68 141%; p < 0.001). In contrast to 81 patients with therapeutic heparinisation (90%, 60-131%) significant decreased concentrations were found in 90 subjects under oral anticoagulant therapy (OAT) in the stable state (78%, 44-125%; p < 0.001). Depending on different INR levels (< 2.5, n = 40: 71%, 63-85%; > 2.5, n = 50: 81%, 68-92%; median and 25th-75th percentile) no significant differences of C4b-BP concentrations could be measured. PMID- 8470057 TI - Enantioselective antiplatelet actions of nipecotamides. AB - Two synthetic racemic nipecotamides, 1-decyl-3-(N,N- diethylcarbamoyl)piperidine hydrobromide (1) and alpha, alpha'-bis[3-(N-benzyl-N-methylcarbamoyl)piperidino] p-xylene dihydrobromide (2) were resolved on a chiral alpha 1-acid glycoprotein semipreparative HPLC column. Thus, rac.1 was resolved into two enantiomers 1A-(+) and 1B-(-); rac.2 was separated into the optical antipodes 2A-(-) and 2C-(+), and the meso diastereomer 2B-(0). Also on a preparative scale, 97% pure 2C was obtained via diastereomeric salt formation using dibenzoyl-L-(-)-tartaric acid. The individual isomers were evaluated for their platelet aggregation inhibitory potency. In inhibiting ADP-induced aggregation of human platelets in vitro, 1B-( ) was 4 times more potent than its optical antipode 1A-(+), and 2C-(+) was 6 times as active as 2A-(-); the meso diastereomer 2B-(0) had intermediate activity. With collagen as the 1B-(-) was twice as active as 1A-(+), and 2C-(+), the most active compound in this series (IC50 = 0.96 microM), was 10 times more potent than its antipode 2A-(-). Again, the meso diastereomer 2B-(0) had intermediate activity. These results demonstrate the enantioselective antiplatelet actions of mono- and bis- nipecotamide derivatives. PMID- 8470058 TI - Molecular weight and biochemical profile of a chemically modified heparin derivative, Suleparoide. AB - Recently, a new chemically modified derivative of heparin (Suleparoide, Syntex Laboratories Buenos Aires, Argentina) was introduced for the prophylaxis of thrombosis and treatment of vascular disorders. This agent is claimed to contain a depolymerized, chemically modified, heparin derivative with similar biologic actions as heparan sulfate. To study the pharmacologic profile of this agent, we have defined its molecular weight distribution profile, utilizing a computerized gel permeation chromatographic system equipped with ultraviolet and refractive index detectors. Suleparoide exhibited a normal molecular distribution profile with no contaminants. It exhibited a weight average of 9.3 K DA and an apparent peak MW of 8.0 K DA. Approximately 50% of the molecular components were < 5.0 K DA and 40% > 5.0 K DA. The results from these studies on the mechanisms show that Suleparoide has anticoagulant activity primarily mediated through Heparin Cofactor-II (HC-II) and because of its novel mechanism of action, further investigations on the biochemical profile of Suleparoide are carried out. Global clotting tests such as Activated Partial Thromboplastin Time (APTT), Heptest and Thrombin Time (TT) revealed a concentration dependent effect in all assays. Plasma samples supplemented with Suleparoide exhibited no significant anti-Xa and anti-IIa activities. However, in the HC-II mediated inhibitory assay for IIa, Suleparoide exhibited significant activity. In contrast, the Antithrombin-III (AT III) mediated inhibition of IIa was much weaker. PMID- 8470059 TI - Supranormal antithrombin III levels induced by concentrate administration are ineffective in quenching thrombin generation in acute promyelocytic leukemia. AB - Coagulation abnormalities occurring in patients with acute promyelocytic leukemia (APL) are partially corrected by heparin administration. This study was undertaken to verify if "supra-normal" levels of antithrombin III (AT-III) are similarly able to quench intravascular thrombin generation triggered by APL cells. Eight patients with APL were randomly assigned to receive either 50 U/kg (Group A) or 100 U/kg (Group B) of an AT-III concentrate, starting on the first day of chemotherapy and continuing for 7 days thereafter. Fibrinopeptide A (FPA), prothrombin fragment F1+2 and thrombin-AT III complexes, measured before and 15 minutes after each AT-III infusion, decreased significantly after each infusion, but the effect was minimal and short-lived, despite the achievement of post infusion levels of AT-III activity well above 150% (Group A) or 200% (Group B). Small amounts of heparin were consistently detected in AT-III concentrates and post-infusion plasma samples. The short-lived quenching of thrombin generation after AT-III concentrate could be partially explained by the infusion of heparin, rather than by supranormal AT-III levels. PMID- 8470060 TI - Construction and its expression of a new retroviral vector containing a human blood coagulation factor IX cDNA. AB - We constructed a new factor IX expression vector containing a full length factor IX cDNA. The Moloney Murine Leukemia Virus (MoMLV)-based retroviral vector pLRNL was cloned with the entire coding region of human factor IX down stream of the promoter of Rous sarcoma virus, giving rise to the construct pL9RNL. The GP+E 86 packaging cell was transfected with pL9RNL and two mouse fibroblast cell lines (PA317 and NIH3T3) were infected with the virus generated from PA317 cell. During the 24 hr culture period, the maximum 1.2 micrograms of factor IX was secreted into the medium from 10(6) of GP+E 86 cells. Factor IX in the culture media had the relatively normal procoagulant activity and was barium-citrate precipitated. Western blotting analysis of the barium-citrate precipitates revealed that a single chain 50Kd protein indistinguishable from the plasma-derived factor IX was produced in these three cells. The retroviral expression system that we utilized herein may contribute to the study of recombinant wild type or various mutant factor IX, and to the basic study for the future gene therapy. PMID- 8470062 TI - Decreased plasma protein C levels after high dosage of acetylsalicylic acid. PMID- 8470061 TI - The development of a simple and quick enzyme-linked immunosorbent assay for anti HPA1a (PLA1) antibodies. PMID- 8470063 TI - Consistency of responses to separate desmopressin infusions in patients with storage pool disease and isolated prolonged bleeding time. PMID- 8470064 TI - [Physician--cure yourself?]. PMID- 8470065 TI - [B-preparations--a strong challenge to the medical profession]. PMID- 8470066 TI - [Who will lose her uterus?]. PMID- 8470067 TI - [Is involuntary sterility a disease?]. PMID- 8470068 TI - [Fertilization in vitro--how large a proportion of couples will have a child?]. AB - In Norway, the efficacy and the efficiency of IVF treatment for infertile couples have been questioned. Information about this topic is important for the general public, the infertile population, the gynaecologists and the health authorities. We have followed a cohort of 485 infertile couples accepted for in vitro fertilization treatment. During a 14 month period starting 1 January 1989 a total of 214 women have either delivered or are pregnant in the second or third trimester. This number represents 44% of the 485 women accepted for IVF treatment, irrespective of whether they were treated or not, and 50% of the couples who completed at least one IVF cycle. There was no difference in cycle efficiency (pregnancy rate) between the first to third cycle, but this was significantly lower in cycle 4-6. There was no difference in delivery rate between groups of patients with different diagnoses of female infertility, but an additional male factor reduced the delivery rate significantly. Replacement of cryopreserved/thawed embryos gave a 5% increase in the delivery rate per couple included in the study, and an increase of 13% in the number of deliveries. PMID- 8470069 TI - [Fertilization in vitro--success rates and registration]. AB - There is great uncertainty and concern about the reliability of success rates in IVF. This is because of lack of agreement about what defines success and how this should be measured. Success should be reported on the basis of real birth rates measured against all stimulation cycles and all women accepted for treatment. This is because the purpose of IVF is to alleviate infertility, and couples (or women) who seek treatment will only consider live birth as a successful result. All clinics should be required to submit these results to a national registry in order to retain accreditation by the Ministry of Health. The purpose of the registry is to make information available to couples (or women) about their real chances of giving birth to a child. This will also make it possible to evaluate whether the economic resources are used efficiently, a requirement which may help to standardize the definition of success used in medical journals. PMID- 8470070 TI - [Assisted fertilization--where are we now and where are we going?]. AB - The authors review the development of assisted reproduction, and describe the present status. The efficacy of in vitro fertilization is compared with the results of tubal surgery. A comparison is also made of the efficacy of different assisted reproductive techniques. Future aspects of assisted reproduction are discussed, with particular emphasis on the need for better understanding of the implantation process. This may reduce the need for transfer of multiple embryos, thereby decreasing risk of multiple pregnancies. PMID- 8470071 TI - [Analysis of estrogen receptors in mammary carcinomas. Is immunocytochemical determination after formalin fixation sufficient?]. AB - By application of a monoclonal antibody (Abbott ER-ICA) oestrogen receptors can now be demonstrated and semiquantitated on paraffin sections after fixation in formalin. In a prospective series of 22 breast carcinomas we found that 82% (18/22) were oestrogen receptor positive. The frequency was significantly lower in archival tissue comprising 27 invasive carcinomas (56%) and in 63 intraductal carcinomas (54%). Even lower frequencies were found in recurrences and metastases and none (0/10) of the metastases from tumours of unknown origin were oestrogen receptor positive. It is likely that prolonged fixation in formalin destroys the receptor protein. Immunocytochemical assessment of oestrogen receptor may be the only alternative when dealing with small breast tumours (< 1 cm), in cases of suspected recurrences and in cases of unknown receptor status. PMID- 8470072 TI - [Dyspepsia and life style]. AB - Information on eating habits, life situation and perceived stress was collected from 100 patients who consulted general practitioner because of dyspeptic complaints. This information was compared with information from a control group with no dyspeptic symptoms. The patients reported a higher degree of stress in connection with occupation and family, and more economic worries, than the control group. Patients with ulcus also tended to have a higher consumption of tobacco. There were no significant differences in eating habits or alcohol consumption between the groups. PMID- 8470073 TI - [Aspiration of ganglia in the wrist]. AB - Because of recently published good results we wished to evaluate the therapeutic effect among our own patients of simple aspiration of ganglia near the wrist. We entered 24 consecutive patients referred for operation of wrist ganglia into the study and administered a regimen of up to three aspirations at intervals of four to six weeks. There were five deviants from the protocol. Among the remaining 19 patients the ganglion had disappeared in 13 by the end of the aspiration regimen. However, one year after the first aspiration there had been seven recurrences. Only eight of the original 24 patients underwent surgery. The remainder felt that this was no longer necessary. In our material simple aspiration had little therapeutic effect, but markedly reduced the number of patients operated on for ganglia of the wrist. PMID- 8470074 TI - [Current principles in the treatment of knee ligament injuries]. AB - Knee ligament injuries are the leading cause of disability from injuries occurring during sports. The incidence of these injuries is increasing in Norway, owing to greater participation in recreational and competitive sports. In Norway, the main contributor to anterior cruciate ligament injuries is European team handball where women who compete at a high level sustain a large number of injuries. This paper describes modern principles of diagnosis and treatment of these injuries, based on personal research and a review of the literature. PMID- 8470075 TI - [Head injuries in sports--evaluation during admission, follow-up and routine check-ups]. AB - The authors review head injuries during sport. Among 3,206 such injuries treated at the Regional Hospital, Trondheim, in the course of one year, 12% were injuries to head and face. Minor injuries are classified as. Mild (no amnesia or loss of consciousness), no symptoms, the activity can continue, but one week of rest is recommended. Moderate (amnesia or loss of consciousness < 1 min), medical examination, and two weeks of rest are recommended. Major (loss of consciousness < 5 min), CT scan and one month of rest are recommended. With repeated moderate or triple mild traumas, CT and the possible termination of the sporting season should be considered. Serious head injuries with intracranial pathology will generally disqualify the person from further elite competition. The possible consequences of repeated head injuries during football and other contact sports are stressed, and more regular use of neurophysiologic methods (EEG) and magnetic resonance (MR) in selected cases is recommended. The authors also point out the advantages of using helmets and protective gear, and the doctors' role in advocating such equipment. PMID- 8470076 TI - [Sports in cold climate]. AB - In winter sports, and in some summer sports as well, training and competitions take place under climatic conditions where it is necessary to be aware of the danger of hypothermia. Most of the lesions caused by hypothermia during sports activities are minor ones, but severe hypothermia may also occur. Lesions are encountered most frequently on the face, including the eyes, and on hands, feet and other frontal parts of the body. Special attention must be paid to risk of hypothermia in children. The organizers of sports competitions have a duty to provide proper rooms where athletes suffering from hypothermia can region their proper body temperature, and it should be possible for doctors or paramedics to take care of these and other injured athletes at the stadium, and if necessary accompany them to the nearest hospital. PMID- 8470077 TI - [Health services for physicians. Experiences from a pilot project]. AB - The topic of article is a two-year trial of health service for doctors in the districts of Asker and Eidsvoll, under the auspices of the Akershus branch of the Norwegian Medical Association. The object of the trial was to develop a model for a health service for doctors. All doctors in the selected districts, except those covered by occupational health services, were invited to take part in the trial. Doctors recruited as doctors for colleagues, were given systematic tutoring and teaching throughout the trial period. The authors describe how the trial was organized and carried out, and summarize the practical experience gained so far. They also give a brief account of the continued efforts of the Akershus branch of the Norwegian Medical Association to develop a better health service for doctors. PMID- 8470078 TI - [Physician and patient at the same time. Experiences from participants of a health service trial for physicians]. AB - A health service for doctors was made available in two municipalities. 28 doctors participated in a trial lasting two years. The overall evaluation included an interview by telephone, and the participants were asked to give their opinion of the trial. The response was unanimously positive. Most participants felt a clear need for contact, something which was not always apparent to the doctors' doctor. The participants appreciated the psychosocial aspect of the trial most of all. Lowest marks were awarded to the part dealing with the working environment. Few doctors found it difficult to fit into the patient's role. The selection of doctors' doctors, and their tutoring and preparation for this role, are probably the main factors behind the success of the trial. The evaluation clearly supports the creation of a health service for doctors. PMID- 8470079 TI - [Invasive or transcutaneous measurements of oxygen saturation and blood gases? An evaluation of pulse oximetry and transcutaneous measurement of PO2 and PCO2 during rest and exercise]. AB - Arterial and transcutaneous measurements of the oxygen saturation (SO2), the partial pressure of oxygen (PO2) and the partial pressure of carbon dioxide (PCO2 were compared during rest before and after cycling, and during submaximal and maximal exercise, in 12 adult patients with cystic fibrosis. SO2 was measured non invasively using two different pulse oximeters (Radiometer and Ohmeda, respectively) and PO2 and PCO2 were registered with a transcutaneous electrode (Radiometer). The coefficients of correlation between arterial and transcutaneous values were respectively 0.95 (Radiometer) and 0.85 (Ohmeda) for SO2, 0.77 for PO2, and 0.75 for PCO2. On average the differences between arterial and transcutaneous values were small, but varied by 3-4% (2SD) for SO2, 2.0 kPa for PO2 and 1.0 kPa for PCO2. Our results indicate that pulse oximetry is a reasonably good way of detecting severe arterial hypoxemia during work, whereas the transcutaneous measurements of PO2 and PCO2 show such large variations that this method cannot be recommended for clinical use. PMID- 8470080 TI - [Hysterectomy in Norway. Quality of data and clinical practice]. AB - A nation-wide register of discharges from hospitals was used to analyze the practice of hysterectomy in Norwegian hospitals during the three-year period 1988 to 1990. A total of 10.167 hysterectomies were recorded, 20% of them were subtotal hysterectomies. Incidental appendectomy was performed in 4%. Approximately 60 hospitals performed hysterectomy. At 17 hospitals the number was ten or less per year, while at two hospitals more than 200 hysterectomies were performed per year. The national hysterectomy rate was 164 per 100,000 women or 198 per 100,000 women > or = 15 years. The rate is almost 50% higher than a previously reported rate from the period 1977 to 1978, but is still remarkably low compared with the rates reported in the international literature. PMID- 8470081 TI - [Preoperative fasting]. PMID- 8470082 TI - [Professional secrecy and research]. PMID- 8470083 TI - [Empathy]. PMID- 8470084 TI - [Who is responsible for computerized medical records?]. PMID- 8470085 TI - [Meeting the hospital devil. The only one with complete access to information and unrestricted responsibility in hospitals]. PMID- 8470086 TI - [Local competence--a condition for local development]. PMID- 8470087 TI - [Development of the psychiatric outpatient clinics in Oslo. Thoughts on history and future]. PMID- 8470088 TI - [Physician--a changing role]. PMID- 8470089 TI - [Follow-up and treatment of HIV-positive patients]. PMID- 8470090 TI - Redistribution of epidermal growth factor receptor as a function of cell density, cell-cell adhesion and calcium in human (A-431) cells. AB - Cell surface expression of the epidermal growth factor (EGF) receptor in several cell lines declines as a function of increased cell density and is associated with diminished responsiveness to EGF. However, the mechanism whereby this density-induced down regulation of receptors occurs has not been discerned. In the present study the distribution of the EGF receptor in A-431 cells as a function of cell density using (1) two polyclonal antibodies raised against peptide specific sequences of the EGF receptor that recognize either the cytoplasmic or extracellular domains of the receptor, respectively, and (2) biotinylated EGF, a specific probe for the cell surface receptor is now investigated. Immunolocalization of the receptor using the polyclonal antibodies or the biotin-EGF revealed that the receptor was homogeneously distributed on the cell surface of individual cells, or in cells plated at low density. In contrast, as cell density increased, prominent EGF immunoreactivity and biotin-EGF staining became limited to the periphery of the cells, at sites of cell-cell apposition, and was characterized by a honeycomb pattern, typical of a basolateral distribution. The effects of low Ca++ treatment, known to cause cells to round up and detach from one another, on EGF receptor distribution in cells at high cell density were then examined. Confocal microscopy of immunostained preparations revealed that incubation of high density cultures in Ca(++)-free media for as little as 10 min restored the homogeneous distribution of the EGF receptor and resulted in strong intracellular staining. Three-dimensional reconstruction of serial optical sections revealed that redistribution of the EGF receptor following low Ca++ treatment involved a heretofore undetected 'ruffling', an immunostaining pattern characterized by stripes of intense fluorescence signal interspersed with complete absence of fluorescence. Next, cell-cell adhesion was disrupted with antisera to the cell adhesion molecule E-cadherin. Although the antisera caused cells to detach from one another, eventually leading to cell rounding and redistribution of the EGF receptor, the receptor 'ruffling' immunostaining pattern rendered by the low Ca++ treatment was not detected. These results suggest that an association may exist between the plasma membrane EGF receptor distribution, density-induced EGF receptor down regulation, and the growth effects of low Ca++ observed in previous studies. PMID- 8470091 TI - The Harderian gland of the rodent Octodon degus: a structural and ultrastructural study. AB - Harderian glands from male and female Octodon degus were examined by light and transmission electron microscopy. Two types of secretory units, designated as type I and type II, were observed. Type I secretory units comprise three types of epithelial cells: Cells packed with numerous lipid droplets (Type a), cells with few lipid droplets (Type b), and cells with numerous mitochondria and a very well developed Golgi complex (Type c). Type II secretory units were found exclusively in female Octodon degus and comprised a type of secretory cells which contained numerous basophilic granules in their apical cytoplasm. In addition, in female Octodon degus, clusters of lymphocyte-like cells and plasmatic cells were also observed. The vascularization of the gland appeared very well developed. The most unique feature of the blood supply was the existence of large sinusoidal vessels extremely variable in shape. In the medullar region, the sinsoidal wall adapts its contour to that of the tubuloalveolar surface. Unmyelinated and myelinated nerve fibers were found in the connective stroma of the gland. PMID- 8470092 TI - Histological evaluation of the zonation of colloidal gold uptake by the rat liver. AB - The distribution and endocytotic function of Kupffer cells in the rat liver were studied after administration of fibrinogen stabilized colloidal gold suspensions either by injection directly into the circulatory system of anaesthetized rats or by application to the isolated perfused liver. After exposure to gold particles the livers were perfused with fixative and studied using several microscopic techniques. Gold was predominantly endocytosed by a highly active population of Kupffer cells surrounding the portal spaces resulting in distinct dark patterns around the terminal portal veins. In cross-sections of lobules the pattern appeared as incomplete networks composed of dark triangular areas with distinct borderlines towards light areas concentric with the terminal hepatic veins (central veins). The light areas contained few and relatively inactive small Kupffer cells. A wide variation of conditions gave essentially the same uptake pattern compatible with the concept of microcirculatory zones concentric with the terminal hepatic veins (Lamers et al., 1989; Quistorff and Romert, 1989), but contradicting the traditional view of microcirculatory zones advanced by Rappaport et al. (1954). Since the same pattern developed during conditions of anoxia, it seems that oxygen is not the stimulus for the developmental distribution of Kupffer cells with high endocytotic activity. In vivo and perfusion experiments gave identical patterns, but a higher endocytotic activity of endothelial cells was found in perfused isolated livers. PMID- 8470093 TI - Filamentous actin detected in rat spermatozoa. AB - In this paper we report the positive staining of epididymal spermatozoa and testicular cells (late spermatids and spermatozoa) with fluorescent phallotoxins. Staining is most obvious with rhodamine phalloidin, but is also detectible with NBD-phallacidin. Specific fluorescence is emitted as a linear tract along the dorsal curvature of the head and as an inverted V-shaped structure in what appears to be the anterior aspect of the post-acrosomal region. We conclude that filamentous actin occurs in the heads of rat spermatozoa. Moreover, we speculate that this filamentous actin is concentrated in two regions of the perinuclear theca; in the subacrosomal space along the dorsal curvature of the nucleus, and in the post-acrosomal region in an area termed the ventral spur. PMID- 8470094 TI - The participation of growth factors in simulating the quiescent, proliferative, and differentiative stages of rat granulosa cells grown in a serum-free medium. AB - Ovarian granulosa cells from small antral follicles from immature rats were cultured in a serum-free medium on an extracellular matrix for 10 days with growth factors in an effort to simulate the metabolic states they experience during their differentiation. During in vivo differentiation granulosa cells are initially quiescent, later proliferate and subsequently commence differentiation. With the production of androstenedione by the vascularized theca interna they produce estrogen and when the follicle reaches the preovulatory stage, granulosa cells produce both estrogen and progesterone. Culturing granulosa cells in serum free medium plus FSH, PDGF, or FSH plus PDGF, the cells remain quiescent. The cells proliferate most consistently (as assessed by DNA quantitation) when cultured in FSH, PDGF, TGF alpha, TGF beta and GH, and undergo the first level of differentiation by producing estrogen (assessed by RIA) when cultured in FSH, PDGF, TGF beta, IGF-I and delta 4-A. Further differentiation is achieved in the presence of FSH, PDGF, TGF alpha, bFGF and delta 4-A when the cells produce both estrogen and progesterone similar to their production in preovulatory follicles. Phase contrast photomicrographs were made to monitor cellular shape changes. Electron microscopic analysis of the quiescent and proliferative cells reveal them to contain the normally occurring organelles. After 8 days in culture, cells producing estrogen, and estrogen and progesterone, contain endoplasmic reticulum of the smooth variety, an organelle which, in cooperation with mitochondria, is known to be involved in the production of steroids such as estrogen and progesterone. Therefore, with the addition of one or more growth factors and androstenedione to FSH-containing serum free medium, the simulated conditions are partially reminiscent of the follicular microenvironment, in which granulosa cells cultured on extracellular matrix can exhibit characteristics of growth and differentiation similar to folliculogenesis. PMID- 8470095 TI - Synchrotron X-ray diffraction and histochemical studies of normal and myopic chick eyes. AB - Synchrotron X-ray diffraction patterns were obtained from the cornea and posterior sclera of control and myopic chicks. No significant differences was found in the interfibrillar or in the intermolecular spacing of the collagen fibrils from the corneas of control and myopic chicks. The intermolecular spacing of myopic sclera was shown to be significantly (p < 0.01) higher than in controls. Sclera and cornea from normal and myopic chicks were stained for proteoglycans using the 'critical electrolyte' method of Scott and Orford (1981). In the sclera, two morphologically distinct types of proteoglycans could be distinguished; one small and usually elongated (approximately 20 nm), the other larger and irregularly shaped. The small proteoglycans were seen binding preferentially to the 'd' and 'e' bands of the collagen fibrils. Small proteoglycans were also present within the fibrils, these were usually approximately 10 nm in diameter although sizes up to 30 nm were observed. Longitudinal sections of fibrils revealed that these intrafibrillar proteoglycans were chiefly orientated parallel to the axis of the collagen fibrils, and preferentially located along the gap region of the fibrils. No difference was observed in the binding sites of the proteoglycans between normal and myopic sclera. The larger proteoglycans were also seen aggregated into clumps, which were usually associated with spaces between collagen bundles. The differences between control and myopic sclera appear to be quantitative rather than qualitative suggesting that the scleral expansion in myopia is an enhanced form of normal scleral growth. PMID- 8470096 TI - Localization of fibronectin in the frog skin. AB - In this review, we present structural and ultrastructural localizations of fibronectin (FN) in the larval and adult skin of the frog (Rana esculenta) either in in vivo or in in vitro conditions. The ventral skin of the tadpole contains membrane-associated FN-plaques disposed around the epidermal and dermal cells during their climactic rearrangement. Moreover, lines of fibrillar FN are detected inside the breaks opened in the derived collagen. The ventral skin of the adult frog reveals FN distributed in the three superimposed tissues forming the skin, i.e. the epidermis, the dermis and the subcutaneous tissue. In vivo, the epidermis is devoid of FN except for the mitochondria-rich cells (MRCs) which contain FN cytoplasmic granules. The dermis reveals two distinct collagenous networks showing FN localizations. A vertically-oriented network formed by thick tracts contains axis of fibrillar FN connecting the upper dermis devoid of FN to the FN-rich subcutaneous tissue. In contiguity with an horizontally-oriented network comprises thin tracts formed by clear spaces separating the superimposed collagen bundles of the dermal stratum compactum. These tracts contain aligned FN granules. Inside the thick and thin tracts, the dermal and pigment cells present membrane-associated In vitro (in organ culture conditions) MRCs of the epidermis maintain their FN localization and, in addition, the stratum germinativum cells show cytoplasmic FN granules. Epidermal cells, in the vicinity of the cut edges of the cultivated skin fragment, modify their shape and acquire membrane associated FN-plaques located between desmosomes. The FN localizations in these two collagenous networks of the dermis remain unchanged. In the same way, the FN rich subcutaneous tissue is unmodified. In summary, the FN distribution in the larval skin is related to the cell rearrangement during the metamorphic climax, and, in the adult skin to the cell migration during the wound healing process and the pigment cell patterning. The cell migration is demonstrated, in organ culture conditions, by antiFN serum used as an experimental tool. FN is an important substrate used in the dermal breaks of the larval skin, and in the dermal tracts of the adult skin, both allowing the dermal and pigment cell migration. PMID- 8470097 TI - [The paraspecific immune defense: possibilities and limits]. AB - The paraspecific defense system is the phylogenetically older part of the complex immune system. It enables the organism to immediately attack various foreign substances, infectious germs and toxins when confronted by them. In order to activate the paraspecific immune system with the help of drugs, so-called "paramunity inducers" are employed. The use of paramunization is a new way of prophylaxis and therapy, not only with regard to infections, but also with regard to different other indications. The limitations of paramunization are to be found in genetic defects of the paraspecific immune system, therefore the success of paramunization is dependent on the functioning of the paraspecific defense system. The possibility of developing paramunity inducers that are pyrogen-free, non-toxic and pleotypically effective in pre-clinical and clinical experiments is illustrated through the use of pox and parapox viruses. Inducers based on different pox virus species were effective and safe when used in humans as well as in animals in the field. PMID- 8470098 TI - [The clinical case. Acute skin necrosis in a cat]. PMID- 8470099 TI - [Trace elements in the liver and myocardium of stillborn dairy calves]. AB - Trace element analyses were performed on the livers of 52 and the heart muscle of 19 stillborn dairy calves. All calves originated from one herd and ranged in age from 260 days of gestation up to one day old. In the liver the trace element concentrations (mg/kg fresh weight) were as follows: Fe: 181.3 +/- 173.5; Zn: 74.6 +/- 37.7; Cu: 98.1 +/- 42.6; Mn: 1.4 +/- 0.36 and in the heart: Fe: 54.1 +/- 10.6; Zn: 16.3 +/- 3.8; Cu: 2.5 +/- 0.99; Mn: 0.42 +/- 0.07. Calves from heifers had lower Cu values. The relationship between trace element concentration and content and liver and heart weight is discussed, as are aspects of bioavailability and storage mechanisms as well as clinical signs of trace metal deficiencies. PMID- 8470100 TI - [The suitability of 1-alpha-hydroxycholecalciferol for the prevention of recurrent parturient paresis in dairy cows]. AB - Sixty-four cows with parturient paresis were given a standard treatment of 500 ml calcium gluconate (10.7 g Ca++) infusion solution. Twelve of these cows (experimental group = EG 1) additionally received 420 micrograms 1-alpha hydroxycholecalciferol (1-alpha-OHD3) with 4 mg 25-hydroxycholecalciferol (25 OHD3) by the intramuscular route. A further 9 and 10 cows were given 210 micrograms 1-alpha-OHD3 and 2 mg 25-OHD3 (EG 3) with the calcium infusion, while 10 cows received either 420 micrograms 1-alpha-OHD3 (EG 4) or 210 micrograms 1 alpha-OHD3 (EG 5). Twenty-three cows (EG 2 and 4) which were given a calcium infusion alone acted as controls. The incidence of recurrence could not be reduced by the administration of Vitamin D3 metabolites concurrently with a calcium infusion, although calcium and phosphorus levels were higher between 24 and 48 hours after calcium infusion alone. The combination of 1-alpha-OHD3/25 OHD3 at the higher dosage resulted in the highest calcium levels. PMID- 8470101 TI - [Systematic control of claw health in cows raised in loose housing systems for the total year]. AB - Claw health was systematically checked and recorded in the dairy herd of the experimental and teaching unit at Oberschleissheim. The project started in March 1988 and ended in July 1989. In total 158 dairy cows and 50 heifers of the breeds German Black and White as well as German Simmental were examined for claw health at intervals of six weeks. Heel erosion was diagnosed most frequently, followed by interdigital dermatitis and contusion of the sole. Contusions and ulcerations of the sole were located especially in the claws of the hindleg. More than 90 percent of lameness occurred in the hindleg. Frequency and severity of claw disorders were reduced significantly over the 1.5 year period of systematic veterinary supervision of claw health. Thirty percent of dairy cows were diagnosed as having not any claw disorder at the end of the investigation period. The percentage of dairy cows without any claw disorder was increased by 5-10 percent. Cows of the breed German Simmental in their first lactation were a high risk group for contusions of the sole. The repeatability of the claw measurements of angle of the dorsal wall, length of the dorsal wall and of the heel, height of the heel, diagonal length of the claw and ground surface was usually 0.5 and higher. For the claw disorders heel erosion, interdigital hyperplasia and in part contusions of the sole, fairly high correlations were estimated between heifers and cows as well as between consecutive lactations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470102 TI - [Brush biopsy as a new examination method of the upper respiratory tract in cattle and swine]. AB - Several techniques of cytobrush sampling were developed for morphological examination of upper respiratory tract epithelium in cattle and swine. These techniques were evaluated in 30 cattle and swine each, with an age of two weeks to nine years and three weeks to four years respectively. Optimal anatomical locations for sampling were determined. Three cytobrushes of different shapes were constructed to optimize sampling in animals of different ages. Two out of four cytobrush sampling techniques developed provided sufficient cellular material and worked well under field conditions. Rinsing with 0.9% saline largely eliminated mucus and other interfering substances. PMID- 8470103 TI - [Diagnostic endoscopy and sexoscopy in birds]. AB - The main indication for clinical endoscopy in birds is--beside diagnostic reasons -sex determination in monomorphic avian species. Some typical findings, the technical procedure, important differences to endoscopy in mammals and possible complications are described. PMID- 8470104 TI - [Effect of a paramunity inducer on the incidence of diseases and the plasma cortisol content in Thoroughbred foals before and after weaning]. AB - The effect of the prophylactic application of the paramunity inducer Baypamun on the incidence of diseases among foals (n = 63) in four Thoroughbred studs was evaluated. In a blind study, 38 of the foals received 2 ml of Baypamun intramuscularly while 25 of the foals received a placebo at six and four days before weaning and on the fifth day post-weaning. During the observation period of three weeks, beginning with the first and ending ten days after the last application, 7.9% of the foals treated with Baypamun (3 out of 38) suffered from respiratory infections compared to 24% of the foals treated with placebo (6 out of 25). The blood plasma cortisol concentrations were also measured in 53 of the foals of three studs before and 24 hours after weaning. The cortisol concentration increased in all the foals. However, the increase was significant only for the Baypamun treated foals of one stud while it was significant for the placebo treated foals of all studs (p < 0.01). PMID- 8470105 TI - [Simple diaphragmatic eventration (false diaphragmatic hernia) as the cause of a fatally progressing colic in a horse]. AB - The pathology of a horse is described, in which thoracic trauma with costal fracture and a small diaphragmatic defect later led to entrapment of small intestine in the thorax. PMID- 8470106 TI - [Feed allergy in dogs and cats--not only a gastrointestinal problem]. AB - Immunologically mediated reactions to foods are responsible for up to 10% of all allergic syndromes in dogs and cats. Skin lesions (pruritus, erythema and papules) represent the main manifestation (70 to 80%) compared to only 10 to 15% incidence of gastrointestinal signs in combination with skin problems or alone. Diarrhea, vomiting, low appetite, chronic weight loss, abdominal pain and lethargy are the most common signs involved in gastrointestinal food allergy. There exists no breed or sex predilection in dogs or cats; signs may occur at any time during life time. The immunological nature of the disease can only be guessed at from anamnestic and clinical features and must be verified by presence of lymphocytes, plasma cells, mast cells and eosinophilic granulocytes in histological specimens. At this time, the responsible allergen can only be identified in a restriction diet trial based on food which the animal has not been fed before, given exclusively for at least four weeks to the pet. Changing from one brand of commercial diet to another is not recommended. The diagnosis is conclusively proven by reproducing the symptoms by feeding the original diet after the elimination of signs on the new diet. The pet can then be fed on a commercial diet (or home-made food) without the offending allergen(s). PMID- 8470107 TI - [Ulna growth retardation syndrome in the dog]. AB - Premature closure of the distal ulnar physis leads to medial bowing of the radius, later to lateral deviation of the carpus, and ventral subluxation of the elbow. Diagnosis of this growth disturbance depends on accurate radiographical examination. There are different surgical treatments to allow the radius to grow without impediment. The prognosis depends on early treatment. PMID- 8470108 TI - [Endothelin-1 and endothelin-3 in the plasma of dogs]. AB - The endothelins represent a family of peptides with potent vasoconstrictory effects indicating a role in the regulation of vascular tone. An involvement of endothelins in the pathogenesis as well as pathophysiology of vascular diseases has been proposed. Therefore, the aim of the presented study was to develop the methodology to measure and characterize endothelin-1 (ET-1) and endothelin-3 (ET 3) in the plasma of dogs. Extraction of acidified plasma samples was performed by use of Sep-Pak C18 cartridges and plasma levels of ET-1- and ET-3 immunoreactivity (ET-1-IR; ET-3-IR) were determined by specific radioimmunoassays. The measured ET-immunoreactivities were verified by separation of plasma using high-pressure liquid chromatography (HPLC). PMID- 8470109 TI - [Lysozyme activity in cat feces]. AB - Activity of fecal lysozyme was determined in healthy cats and cats with chronic diarrhea. The established reference value ranged from 0 up to 2.6 micrograms/g feces. Mean activity of the control group was 1.3 +/- 0.9 micrograms/g feces, mean activity of the patient group was 3.4 +/- 3.3 micrograms/g. There was a statistically significant difference between these two values. Nevertheless it was not possible to classify various diseases by evaluating lysozyme activity. In addition to endoscopy and histological examination, determination of lysozyme can be used as screening test and means of assessment for treatment and progress in cats with chronic diarrhea. PMID- 8470110 TI - [Propofol--a short-term narcotic--tested in gastroduodenoscopy in the cat]. AB - The injection anaesthetic propofol (Disoprivan) was used in 85 cats for performing gastroduodenoscopy. Anaesthesia and feasibility for executing endoscopy were evaluated. Two cats suffered from a transient (30 sec) respiratory arrest. In any other cases stable cardiovascular and acceptable respiratory conditions were observed. The endoscopy was easy to perform and no emesis was induced. Anaesthesia of the cat with propofol can be very well controlled. It is characterised by gentle induction and a recovery free from excitation. PMID- 8470111 TI - [Sugar diffusion test, an adjuvant method for the diagnostic differentiation of streptococci of different serological groups]. AB - A sugar differentiation test which allows the differentiation of streptococcal serological groups by means of visual comparison of degree of haemolysis is introduced. The test uses the reagents glucose, lactose and aesculin and is both time- and cost-effective. PMID- 8470112 TI - Differential expression of the metallothionein gene in liver and brain of mice and rats. AB - Expression of the metallothionein I (MT-I) gene was studied in liver and brain of control mice and rats, as well as following administration of Cd and lipopolysaccharide (LPS). Time-course studies revealed that MT mRNA reached a maximum in liver of both mice and rats 6 hr following treatment with Cd or LPS. MT mRNA from control and Cd- and LPS-treated rat brains could not be detected by Northern-blot analysis of total RNA, but Northern analysis with poly(A)-enriched RNA revealed that induction of MT mRNA in rat brain does occur with both Cd and LPS treatment. In contrast, mouse brain MT mRNA was easily detected by Northern blot analysis of total RNA. It was also clear from Northern-blot analyses of both mouse and rat brain that LPS induced more MT mRNA than did Cd. Quantitation of MT mRNA by solution hybridization revealed that Cd and LPS induced similar amounts of MT mRNA in livers of mice (about 0.64 fmol/micrograms total RNA by Cd and 0.68 by LPS) and rats (about 0.23 fmol/micrograms total RNA by Cd and 0.21 by LPS). Therefore, both inducers increased MT mRNA about threefold more in mouse liver than in rat liver. In mouse and rat brain, LPS induced about twice as much MT mRNA as did Cd (about 0.08 fmol/micrograms total RNA by Cd and 0.16 by LPS in mice and about 0.006 fmol/micrograms total RNA by Cd and 0.008 by LPS in rats). However, the actual amount of MT mRNA induced in rat brain by either inducer was minimal compared to that in mouse brain. In fact, Cd induced 13 times more MT mRNA in mouse brain than in rat brain, and LPS induced about 20 times more MT mRNA in mouse brain than in rat brain. Cd distribution to liver was similar in both mice and rats, but the Cd concentration in mouse brain was about 60% more than that in rat brain. Distribution of LPS was also similar in mouse and rat livers, as well as in mouse and rat brains. Therefore, there exists a difference in the expression of MT gene in both liver and brain of mice and rats, the expression in mice being higher than that in rats. These findings suggest that such differential expression of the MT gene cannot be entirely accounted for by the difference in the tissue distribution of inducers. Other tissue-specific and species-specific factors controlling MT gene expression appear to be involved. PMID- 8470113 TI - Temporal relationship of changes in hepatobiliary function and morphology in rats following alpha-naphthylisothiocyanate (ANIT) administration. AB - These studies were designed to evaluate ANIT-induced changes in both hepatobiliary function and morphology during the onset, progression, and recovery of ANIT-induced cholestasis. A single oral dose of 150 mg/kg of ANIT or vehicle was administered by gavage to male Sprague-Dawley rats and hepatobiliary structure and function were evaluated 16, 24, 48, 72, and 168 hr later. Increased hepatocellular tight junction permeability, increased serum bile acids, and decreased bile acid excretion were observed 16 hr after ANIT administration. At 24 hr, bile flow was decreased in ANIT-treated rats, an effect accompanied by increased tight junction permeability, decreased bile acid excretion, and decreased erythritol clearance (estimate of canalicular flow). In addition, scattered small loci of hepatocellular necrosis accompanied by an inflammatory cell response were observed in ANIT-treated rats at this time, with no microscopic evidence of bile duct obstruction (BDO). These data suggest that the onset of ANIT-induced cholestasis was associated with hepatocanalicular changes and not BDO. In contrast, at 48 and 72 hr after ANIT treatment, cholestasis was more profound and was accompanied by mild hepatocellular necrosis and widespread BDO. Hepatocyte tight junction permeability in ANIT-treated rats was not different from controls at 72 hr. These data suggest that the pathogenesis of ANIT-induced cholestasis is biphasic; the onset of cholestasis appears to be associated with changes in hepatocanalicular function and increased tight junction permeability whereas the later and more profound phase of cholestasis appears to be related to a combination of BDO and hepatocellular dysfunction. The time course of biochemical and morphologic changes following ANIT treatment further suggests that the pathophysiologic changes during the onset or initiation phase of cholestasis differ from those involved in the later and more profound phase of ANIT-induced cholestasis. PMID- 8470114 TI - Nephrotoxicity of repeated injections of cadmium-metallothionein in rats. AB - Cadmium-metallothionein (Cd-MT) may have a role in the pathogenesis and irreversibility of Cd nephrotoxicity. In the present study, rats were injected with 0.3 mg Cd/kg body wt per week as Cd-MT for 5 consecutive weeks and a group of rats (n = 3) was killed 24 hr after each injection. A group of three rats was kept for an additional week after the 5 weeks of Cd-MT injection for recovery. After the first injection, urinary Cd and protein levels and kidney/body wt ratio were increased. The electrophoretic pattern of urinary protein showed increased excretion of low-molecular-weight proteins, especially after the first injection of Cd-MT. Tubular cell necrosis occurred after the first week with renal Cd levels of only 10 micrograms/g and gradually progressed to severe necrosis with inflammation in 3 weeks and then to interstitial fibrosis in 5 weeks. The levels of Cd and MT in kidney increased with repeated injection of Cd-MT, but renal Cd was about 40 micrograms/g after 5 weeks of injection. Urinary Cd and MT levels progressively increased during the Cd exposure period, but returned to pretreatment levels during the sixth week (recovery period). Renal cell necrosis and inflammation were absent at the sixth week, but interstitial fibrosis persisted. This study indicates that nephrotoxicity of Cd in this model is related to urinary excretion of Cd-MT and that renal cell injury may be independent of Cd in the renal cortex. Nephrotoxicity occurs at levels much lower than the proposed critical concentration for Cd (200 micrograms Cd/g) following long-term exposure to CdCl2. However, in the absence of continued Cd exposure from liver or circulation, the Cd-MT-induced renal damage is reversible. PMID- 8470115 TI - Single dose blood toxicokinetics of methacrylonitrile in the F344 rat. AB - Methacrylonitrile (MAN) is a widely used industrial chemical. Minimal information is available on its effects or toxicokinetics; therefore, current investigations were undertaken as part of an overall effort to characterize MAN toxicity in laboratory animals. Groups of male F344 rats were administered MAN intravenously (29, 58, or 116 mg/kg) or perorally (58 mg/kg). Blood samples were collected at various time points after dosing and serum MAN concentrations were measured. Concentration versus time profiles were characterized by two phases and a two compartment model was selected to fit the data. Toxicokinetic parameters were determined using Simusolv. The 39-min terminal half-life shows that 99% of an i.v. dose is eliminated in less than 5 hr, suggesting that the potential for MAN bioaccumulation is minimal. The volume of distribution at steady-state (747 ml/kg) indicates little distribution of MAN into tissues. Clearance is higher at 29 mg/kg than at the two other doses, suggesting that MAN elimination is saturable at doses above 29 mg/kg. MAN disposition is route-dependent. Approximately 36% of the i.v. dose was exhaled as unchanged MAN, while only 18% was eliminated via this route following po administration. MAN disposition data also suggest that a significant first-pass metabolism may occur because a higher percentage of metabolites was produced following oral vs i.v. administration. Perorally, 39% of the dose was exhaled as CO2 and 22% was excreted into the urine as metabolites over the 24-hr dosing interval. In comparison, following i.v. delivery, 26% of the dose was exhaled as CO2 and 16% was excreted into the urine as metabolites. About equal amounts of acetone were excreted following administration by either route. This information may prove useful in designing long-term toxicity studies for MAN by the National Toxicology Program and in interpreting the results of such studies. PMID- 8470116 TI - Apoptosis as a mechanism of tributyltin cytotoxicity to thymocytes: relationship of apoptotic markers to biochemical and cellular effects. AB - Recent in vitro studies have suggested that activation of apoptosis could account for the profound depletion of cortical thymocytes, which characterizes tributyltin (TBT) immunotoxicity. However, it has also been shown that TBT disrupts macromolecular synthesis and cellular energetics to an extent that might be expected to interfere with the initiation of apoptosis. The purpose of these studies was to further evaluate the morphological and biochemical characteristics of thymocyte killing by TBT and to relate this to key cellular processes. Ex vivo thymocyte cultures from immature rats were treated with bis(tri-n-butyltin) oxide (TBTO) at concentrations ranging from those which rapidly produced necrosis (5-10 microM), down to cytotoxic but subnecrotic concentrations (0.1-2 microM). In cells exposed to TBTO concentrations that caused a rapid and near maximal inhibition of protein synthesis, it remained possible to demonstrate the stereotypic internucleosomal DNA cleavage and morphological changes indicative of apoptosis. Further confirmation that apoptosis was occurring independently from protein synthesis was provided by the absence of a protective effect following cycloheximide pretreatment. Apoptosis still occurred in TBTO-treated thymocytes although intracellular ATP levels were depressed to 20% or less of control values. Cytoprotective effects were noted with the intracellular Ca2+ chelators BAPTA-AM and Quin-2 AM, and also with zinc. Cell killing by TBTO occurred without overt disturbance of thymocyte cell cycle parameters. These results indicate that thymocyte apoptosis stimulated by TBT exposure occurs independently of a requirement for protein synthesis and does not require fully conserved cellular energetics. PMID- 8470117 TI - Modeling blood/plasma concentrations in dosed feed and dosed drinking water toxicology studies. AB - A computer model for predicting blood/plasma concentrations of test chemicals in dosed feed and dosed drinking water toxicology studies was developed. The model was constructed based on linear theory. The animal's feeding and drinking habits and the linear disposition kinetics of the test chemical obtained after a bolus gavage dose were built into the model. Blood/plasma concentrations of oxazepam and pentachlorophenol in dosed feed and dosed drinking water studies were predicted and compared with the experimentally determined data. The model proved highly reliable in predicting the blood/plasma concentrations of test chemical in dosed feed and dosed drinking water studies. The results suggest that if the kinetics of test chemicals fit a one-compartment model then bioaccumulation of the test chemical will occur in dosed feed or in dosed drinking water studies when absorption half-lives are less than 1.38 hr and elimination half-lives are longer than 5 hr. The extent of accumulation is mainly dependent on the elimination half-lives. For chemicals with absorption half-lives less than 1.38 hr and elimination half-lives less than 2 hr, the extent of bioaccumulation will be minimal. Blood/plasma concentrations of test chemicals in rats and mice will fluctuate daily and a quasi-steady state will be achieved after ad libitum exposure to dosed feed or dosed drinking water for approximately 4 days. If a daily 12-hr light cycle is used with the light cycle starting at 7:00 AM, the expected peak and trough blood concentrations in dosed feed studies will occur approximately in the early morning (5:00 AM) and in the late afternoon (4:00 PM), respectively. Similar results were obtained for dosed drinking water studies. The model should be applicable to dosed feed and dosed drinking water studies using other species. PMID- 8470118 TI - Alterations in alveolar type II cell metabolism induced by tetrandrine and other alkaloids. AB - Tetrandrine (TT) and other bisbenzylisoquinoline alkaloids have been used in China as a treatment for fibrotic lung diseases. Because of their potential use as pulmonary therapeutic agents, we studied the effects of some of these compounds on energy metabolism in isolated rat alveolar type II cells, i.e., cells which play a critical role in maintaining normal lung function. Incubation of type II cells with most of the alkaloids produces a reduction in cellular ATP content. However, there is no effect of the alkaloids on cellular oxygen consumption. All of the alkaloids which produce reductions in cell ATP levels cause increases in internal calcium levels of type II cells. Incubation of the cells with the calcium ionophore, 4-bromo A-23187, leads to increased amounts of intracellular calcium and reductions in ATP levels, but has no effect on oxygen consumption. Exposure of isolated lung mitochondria to calcium produces a concentration-dependent reduction in ATP synthesis with no effect on mitochondrial oxygen consumption. Direct exposure of mitochondria to TT has no effect on ATP synthesis. These results are consistent with the notion that the alkaloids produce an increase in type II cell internal calcium levels which, in turn, leads to reduced rates of mitochondrial ATP synthesis. PMID- 8470119 TI - Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota. AB - In this study we demonstrate the uses of radiometric assay to detect anticholinesterases in a human population (N = 80) exposed to a broad spectrum of pesticides. The assay is nondilutional. Therefore, anticholinesterase (AChE) agents with low binding affinity can be detected. Our initial results show statistically significant exposure-related decreases in either red cell (AChE) or plasma cholinesterase activity ((butyrl)cholinesterase; BuChE) occurred not only among pesticide appliers who use organophosphates, but also among appliers of the fumigant phosphine. These data extend earlier observations made in laboratory animals exposed to this fumigant. Significant exposure-related decreases in AChE activity were seen in herbicide appliers and appear to be associated with exposure to the herbicide 2-methoxy-3,6-dichlorobenzoic acid. There was no evidence of exposure-related decreases in BuChE activity in herbicide appliers. Our in vivo data, coupled with preliminary in vitro studies of phosphine (50% AChE inhibition, 10 ppm) and 2-methoxy-3,6-chlorobenzoic acid (50% AChE and BuChE inhibition, 70 ppm), suggest that the radiometric assay may be used to detect a broader spectrum of biologically active anticholinesterase agents. PMID- 8470120 TI - Contrasting effects of 1,1,1-trichloroethane on [14C]vinyl chloride metabolism and activation in hepatic microsomes from phenobarbital- and isoniazid-treated rats. AB - The interaction of 1,1,1-trichloroethane (TCE), a widely used chlorocarbon solvent, on the metabolism and activation of [14C]-vinyl chloride in rat hepatic microsomes was investigated to determine the effects of combined exposures to these compounds. In microsomes from phenobarbital (PB)-treated rats, TCE increased vinyl chloride-protein binding and vinyl chloride aqueous metabolite formation over twofold when vinyl chloride 0.32% (v/v) and TCE (0.65%) are incubated together. In contrast, under similar incubation conditions, TCE inhibited vinyl chloride metabolism and protein binding up to 45% in microsomes from isoniazid-treated animals. TCE also inhibited vinyl chloride metabolism and binding in microsomes from untreated rats, but to a lesser degree. Like the effect of TCE on vinyl chloride-protein binding, TCE increased vinyl chloride binding to DNA approximately 130% in microsomes from PB-treated rats, yet inhibited vinyl chloride-DNA binding in microsomes from isoniazid-treated and untreated animals. Consistent with TCE effects on vinyl chloride binding and aqueous metabolite production, TCE further increased cytochrome P450 loss due to vinyl chloride metabolism in microsomes from PB-treated rats, but was inhibitory to cytochrome P450 loss due to vinyl chloride metabolism in microsomes from isoniazid-treated and untreated rats. These data demonstrate that the relatively metabolically inert solvent, 1,1,1-trichloroethane, can directly increase vinyl chloride metabolism and activation catalyzed by the phenobarbital-inducible isozymes, but is inhibitory toward vinyl chloride metabolism catalyzed by the isoniazid-inducible CYP2E1. PMID- 8470121 TI - Effect of dose on the metabolism of 1,1,2,2-tetrabromoethane in F344/N rats after gavage administration. AB - 1,1,2,2-Tetrabromo[U-14C]ethane ([14C]TBE) was used to study the metabolism of TBE in rats. Three graded doses of TBE (1.17, 13.6, and 123 mg/kg; 1 microCi 14C/rat at each dose) were administered by gavage to three groups of four rats each. Excreta samples were collected at various time intervals up to 96 hr. Following euthanization, 14C activity was measured in the excreta, tissues, and carcass. The fraction of the dose exhaled as volatile metabolites of TBE, excluding 14CO2, was approximately 9-10% higher in rats given the high dose of TBE compared to that in rats given either the low or the medium dose. The fraction excreted in the urine decreased with increasing TBE dosage. 1,2 Dibromoethylene and tribromoethylene were identified as exhaled metabolites at the high dose. Three major urinary metabolites were identified: dibromoacetic acid, glyoxylic acid, and oxalic acid. The results of this study indicate that the metabolism of TBE was linear up to a dose of 13.6 mg/kg, but the contribution of various TBE metabolic pathways was different at a dose of 123 mg/kg. PMID- 8470122 TI - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the epidermal growth factor receptor in hepatic plasma membranes of rainbow trout (Oncorhynchus mykiss). AB - Time- and dose-dependent alterations in epidermal growth factor receptor (EGF-R) ligand binding and protein kinase activity were observed in hepatic plasma membranes of TCDD-treated rainbow trout. Trout were dosed by a single ip injection of TCDD in a corn oil vehicle. A single ip injection of TCDD (10 micrograms TCDD/kg body wt) caused a maximal reduction of EGF binding to hepatic plasma membranes by 10 days post-treatment and remained reduced until Day 40. EROD activity in the liver microsomes of TCDD-treated trout increased relative to that in untreated fish over the course of the study. Protein kinase C and tyrosine kinase activity as well as EGF-receptor phosphorylation was greater in livers of treated fish than in those of control fish within 5 days but returned to control levels by 40 days postinjection. In a dose-response study, EGF binding was reduced in a dose-dependent manner with an ED50 of 0.17 micrograms TCDD/kg wet wt while EROD activity was induced with an ED50 of 0.79 micrograms TCDD/kg. The reduction in EGF binding was correlated to an increase in EROD activity, protein kinase C activity, and tyrosine kinase activity but was negatively correlated to EGF-receptor phosphorylation. Of the parameters examined in both the time-course and dose studies, protein kinase C was the best predictor of the reduction of EGF binding to hepatic plasma membranes of rainbow trout. The results from this study are consistent with the hypothesis that the mode of action of TCDD on the EGF receptor is in part mediated through the protein kinase C activity. It also suggests that the toxic mode of action of TCDD is similar in rainbow trout and mammals. PMID- 8470123 TI - The nongenotoxic hepatocarcinogen Wy-14,643 is an uncoupler of oxidative phosphorylation in vivo. AB - Wy-14,643 is a potent nongenotoxic hepatic carcinogen and peroxisome proliferator in rodents; however, the mechanism by which it causes tumors remains unknown. In previous work it was demonstrated that Wy-14,643 caused a dose-dependent uncoupling of oxidative phosphorylation (half-maximal effect = 100 microM) in isolated mitochondria (Keller et al., 1992, Biochim. Biophys. Acta, 1162, 237 244); therefore, the purpose of this study was to determine if uncoupling occurred in vivo under conditions which lead ultimately to tumors. Rats were fed Wy-14,643 (0.1%) in ground laboratory chow for 1, 21, 75, and 105 days. As expected, activity of the peroxisomal marker enzyme, acyl-CoA oxidase, was increased about eightfold in liver homogenates during the first 3 weeks of treatment, confirming the induction of peroxisomes. Basal rates of oxygen uptake by the perfused liver were increased significantly by Wy-14,643 treatment at all time points studied, consistent with the hypothesis that oxidative phosphorylation was uncoupled. Basal rates of oxygen uptake of about 130 mumol/g/hr were increased by over 20 mumol/g/hr in rats fed Wy-14,643 in their diet for 10 weeks. Concomitantly, rates of urea synthesis from ammonia, a process highly dependent on ATP supply, were reduced significantly in the perfused liver from 104 mumol/g/hr in control livers to 13 mumol/g/hr in livers from rats treated with Wy-14,643 for 75 days. Taken together, these data indicate that energy supply is disrupted in vivo due to uncoupling of oxidative phosphorylation by Wy-14,643. PMID- 8470124 TI - Effect of cumulative exposure on nasal response to ozone. AB - To assess the potential health risks associated with exposure to low levels of ozone, it is essential to know if the ozone-induced responses are dependent on cumulative exposures or on the peak concentrations. To answer this question female F344/N rats, 11-13 weeks of age, were exposed to a matrix of equal concentration x time values that included exposures to 0, 0.12, 0.24, and 0.48 ppm ozone for 3, 6, 12, or 24 hr. the response of the nasal epithelium was measured as induced DNA synthesis determined by the uptake of bromodeoxyuridine (a thymidine analog) into epithelial cells lining the nasal anterior maxilloturbinates. No increased DNA synthesis was observed in rats exposed to 0.12 ppm ozone for any of the time periods. For exposures higher than 0.12 ppm ozone, the response of the nasal epithelium was similar for equal cumulative exposures. The responses, however, were not linearly related to the cumulative (concentration x time) exposures. It appeared that some mitigating factor was present which decreased the responses at the higher cumulative exposures. No frank toxicity or cellular necrosis was observed, indicating that sublethal cell damage was sufficient to induce DNA synthesis. A simple mathematical model was developed to describe the relationship between ozone exposure and the induction of DNA synthesis in the nasal epithelium. The model predicted that the threshold concentration of ozone for inducing DNA synthesis in the nasal epithelium was 0.1 +/- 0.1 ppm. For one measure of ozone toxicity (induced DNA synthesis) at a sensitive site in the respiratory tract (maxilloturbinates), the effects of ozone were dependent on cumulative exposures at concentrations > 0.12 ppm and within the time and concentration ranges used in this study. PMID- 8470125 TI - Induction of cytochrome P450-dependent monooxygenases in hamster tissues by fasting. AB - The effects of fasting on liver, kidney, and lung monooxygenases were studied using hamsters starved for 4 days. Fasting treatment increased microsomal cytochrome P450 content and NADPH-cytochrome P450 reductase activity in kidney and lung. The treatment caused significant increases of aniline hydroxylation, N nitrosodimethylamine demethylation, and 7-ethoxycoumarin O-deethylation activities in the liver, kidney, and lung. Fasting caused a threefold increase of benzphetamine N-demethylation activity in lung and a 25% increase in liver and had no effect in kidney. Benzo[a]pyrene hydroxylation activities in the fasted hamster liver, kidney, and lung were higher, lower, and similar to the controls, respectively. Gel electrophoresis of tissue microsomes from control and fasted hamsters revealed that fasting enhanced the intensity of protein band(s) in the P450 molecular weight region. Immunoblotting of the microsomal proteins showed that fasting induced a protein crossreactive with rabbit antibody raised against human P450 2E1 in hamster liver, kidney, and lung. Immunoblotting analysis using mouse monoclonal antibody 2-66-3 raised against rat P450 2B1 revealed that fasting induced an immunorelated protein preferentially in hamster lung, with minimal effects on liver and kidney. Protein blots probed with mouse monoclonal antibody 1-12-3 indicated that fasting induced a protein related to P450 1A1 in hamster liver, kidney, and lung. These results demonstrate that fasting causes a variety of inductive effects on the enzyme components and catalytic activities of monooxygenase systems as well as on the P450s 2E, 2B, and 1A in the hamster tissues. PMID- 8470126 TI - Physiological model for the pharmacokinetics of methyl mercury in the growing rat. AB - We describe a physiological pharmacokinetic model for methyl mercury and its metabolite mercuric mercury in the growing rat. Demethylation appears to occur in both host tissues and gastrointestinal flora with elimination dominated by biliary secretion of inorganic mercury and by transport of methyl mercury into the gut lumen followed by substantial bacterial metabolism. Biliary transport of both organic and inorganic mercury is modeled in terms of the known secretion of glutathione from the hepatic pool. At 98 days following an oral tracer dose of 203Hg-labeled methyl mercury chloride, 65% of the administered dose had been recovered in the feces as inorganic mercury and 15% as organic mercury. Urinary excretion is a minor elimination route, accounting for less than 4% of the dose as methyl mercury and 1% of the dose as inorganic mercury. Irreversible incorporation of the mercurials into hair is a significant route of elimination. Ten percent of the administered dose was contained in the hair shed during the 98 days and over 12% of the dose (almost 90% of the body burden) remained in the hair at the end of that time period. Apparent ingestion of hair by the rats during grooming represents a novel form of toxin recirculation. Transport of both chemical species between blood and tissues is bidirectional and symmetric with relatively slow movement into and out of the brain. Transport mechanisms for both mercurial species are discussed in the context of capillary transport physiology and the blood-brain barrier to small molecules and proteins. PMID- 8470128 TI - Spider venoms are not suitable insecticides. PMID- 8470127 TI - The effect of 1-chloro-2,4-dinitrobenzene exposure on antigen receptor (CD3) stimulated transmembrane signal transduction in purified subsets of human peripheral blood lymphocytes. AB - The intracellular low-molecular-weight thiol glutathione (GSH) is an important scavenger of free radicals and plays a role in the maintenance of the redox status of protein sulfhydryl groups. We have previously shown that human peripheral blood lymphocytes sorted on their basal GSH content proliferate proportionately to their GSH levels, and that an early event in lymphocyte activation appeared to be dependent on GSH. We have now analyzed transmembrane signal transduction in cells treated with 1-chloro-2,4-dinitrobenzene (CDNB), a GSH-depleting agent. Transmembrane signal transduction was measured as changes in intracellular free calcium and in protein tyrosine phosphorylation after stimulation with anti-CD3 monoclonal antibody. The results show a CDNB dose dependent reduction in GSH content, the magnitude of intracellular free calcium mobilization, and the extent of tyrosine phosphorylation of several proteins, including phospholipase C-gamma 1. This suggests a role for GSH and/or protein thiol redox status in one of the earliest events controlling the ability of lymphocytes to respond to important proliferative signals in their environment and implies that agents which deplete lymphocyte GSH may be immunosuppressive through effects on CD3/T cell receptor-dependent transmembrane signal transduction. PMID- 8470129 TI - Influence of initial toxicity and extraction procedure on paralytic toxin changes in the mussel. AB - Farmed mussels were artificially contaminated with a pure culture of an Alexandrium tamarense toxic strain (MOG 835), to assess the effect of initial toxicity on paralytic toxin change during the depuration process. As previously observed in mussel, gonyautoxin GTX2 is eliminated more slowly than other gonyautoxins. A toxic level (1300 micrograms PSP per 100 g meat) is required to produce a drastic change in the depuration course, i.e. a 'fast' depuration rate followed by a 'slow' one. Below this threshold, decontamination becomes slower as the proportion of GTX2 increases over the time course. Although GTX2 is slowly eliminated during the depuration process, it is also formed in increasing quantities during the contamination phase. It remains to be determined whether changes in GTX2/GTX3 ratios are due to chemical or biological transformation. PMID- 8470130 TI - Isolation of a myotoxin from the venom of Agkistrodon contortrix laticinctus (broad-banded copperhead) and pathogenesis of myonecrosis induced by it in mice. AB - A myotoxin was isolated from the venom of the broad-banded copperhead (Agkistrodon contortrix laticinctus) by HPLC using anion and cation exchange chromatography. The toxin has a mol. wt of approximately 14,000 and has a pI greater than 9. It does not have phospholipase A activity, but does induce myonecrosis of skeletal muscle cells characterized by a hypercontraction of myofilaments. Electron microscopic analysis showed that the myotoxin appears to disrupt the sarcolemma of skeletal muscle cells. ACL myotoxin is very similar in mol. wt, amino acid composition, and myotoxic activity to myotoxins isolated from the venoms of Bothrops asper and Bothrops nummifer from Central America, suggesting that homologs of this toxin may be found in other crotaline snake venoms. PMID- 8470131 TI - Effect of bilineobin, a thrombin-like proteinase from the venom of common cantil (Agkistrodon bilineatus). AB - A thrombin-like proteinase, named bilineobin, was isolated from Agkistrodon bilineatus venom by Sephadex G-75, DEAE-Sephacel and Heparin-Sepharose CL-6B column chromatography. The purified enzyme has a mol. wt of 57,000 and catalysed the hydrolysis of arginine esters and thrombin substrates Boc-Val-Pro-Arg-MCA and Boc-Asp(OBz)-Pro-Arg-MCA. Although bilineobin converted fibrinogen into fibrin resulting in the production of fibrinopeptides, the activity was relatively low (0.65 NIH units/mg). Fibrinopeptides released upon hydrolysis by this proteinase were identified as fibrinopeptide A (FpA) and fibrinopeptide B (FpB) by measuring fast atom bombardment (FAB) mass spectra and amino acid sequence. This indicates that bilineobin hydrolyses the Arg(19)-Gly(20) bond in the A alpha chain and the Arg(21)-Gly(22) bond in the B beta chain of the bovine fibrinogen molecule. Kinetic study of FpA and FpB release reveals that bilineobin has a preference for cleaving the B beta chain. In addition, bilineobin is resistant to thrombin inhibitors such as hirudin. These suggest that the mechanism of action of bilineobin is similar but not identical to that of thrombin. It was demonstrated that the NH2-terminal region of bilineobin has significant similarities in sequence with thrombin-like proteinases from other snake venoms; however, only three residues were common with thrombin up to residue number 24. PMID- 8470132 TI - Binding of myotoxin a to cultured muscle cells. AB - The binding of radiolabeled myotoxin a to various cultured cell lines was evaluated. One rat skeletal muscle-derived cell line, L8, bound substantially more myotoxin a than did all all other cell lines examined. Several biophysical parameters of myotoxin a-L8 binding were determined. Binding was saturable with a moderate binding affinity. Scatchard analysis and Hill plots indicated a single class of binding sites. The binding was reversible, as demonstrated by chase experiments. Radiolabeled myotoxin a bound to the cell surface at a site inaccessible to the general protease, pronase. Specificity and biological relevance of the binding was suggested by competition with unlabeled toxin and various peptides derived from the toxin. Biologically active peptides, corresponding to the N- and C-terminal sequence of myotoxin a, competed with radiolabeled toxin for L8 binding. It was concluded that the L8 system is a suitable cell model to study myotoxin a mechanism of action. PMID- 8470133 TI - Antagonism of the myotoxic effects of Bothrops jararacussu venom and bothropstoxin by polyanions. AB - The effects of heparin and other polyanions on the myotoxicity of Bothrops jararacussu venom and purified bothropstoxin (BthTX) were investigated. The release rate of creatine kinase (CK) from isolated extensor digitorum longus muscle and the plasma CK activity of mice were used to quantify the results. The myotoxic effects of B. jararacussu venom or BthTX were inhibited by preincubation of these agents with one of the following: a heterogeneous heparin preparation (designated 'heparin'), low mol. wt heparin (H-4500) or dextran sulfates (DS-8000 and DS-500,000). Non-sulfated dextran (D-40,000) and two chondroitin sulfates were ineffective. The antimyotoxic effects of the polyanions are ascribed to their forming inactive acid-base complexes with the basic myotoxins of Bothrops venoms. Gel-filtration experiments in Sephadex provided direct evidence for complex formation between heparin and BthTX. Intravenous (i.v.) administration of H-4500 or DS-8000 opposed the increase in plasma CK activity induced by a subsequent i.m. injection of venom or BthTX. In contrast, pretreatment with i.v. heparin or DS-500,000 enhanced the venom-induced increase in plasma CK activity. This effect was not observed (1) when the animals were treated with a polyvalent antivenom, which inhibits the coagulation and local stasis induced by Bothrops venoms, and (2) when BthTX, which has no thrombotic or hemorrhagic properties, was the myotoxic agent. The potentiation of the venom-induced increase in plasma CK activity by heparin and DS-500,000 is ascribed to improved washout of the CK released from damaged fibers, because of the anticoagulant properties of the drugs. PMID- 8470134 TI - Effects of stonefish (Synanceia trachynis) venom on murine and frog neuromuscular junctions. AB - The neuromuscular toxicity of stonefish (Synanceia trachynis) venom was characterized by electrophysiological and electron microscopic examination of isolated murine and frog nerve-skeletal muscle preparations exposed to various concentrations of venom. Low concentrations of venom (2.5-10 micrograms/ml) acted presynaptically by causing release and depletion of neurotransmitter from the nerve terminal. The response was Na+ channel-independent (resistant to tetrodotoxin), required the presence of either Ca2+ or Mg2+, and was observed with botulinum neurotoxin-paralyzed nerve-muscle preparations. Higher concentrations of venom (100-300 micrograms/ml) acted postsynaptically and presynaptically. They caused irreversible depolarization of muscle cells and microscopically observable muscle and nerve damage. We conclude that the previously observed neuromuscular toxicity of stonefish venom is a consequence of the venom's dose-dependent, presynaptic and postsynaptic actions at the myoneural junction. PMID- 8470135 TI - Identification and characterization of tox21A: a mite cDNA encoding a paralytic neurotoxin related to TxP-I. AB - A cDNA library established from polyadenylated RNA isolated from the predatory mite Pyemotes tritici was screened for cDNAs homologous to tox34, a cDNA encoding an insect-selective paralytic neurotoxin known as TxP-I. Most of the cDNA inserts of homologous clones were shorter or of equal length to tox34 but a few were longer. Further investigation into the nature of these longer clones led to the identification, sequencing and expression of a distinct cDNA referred to as tox21A. This cDNA is predicted to encode a polypeptide which shares approximately 83% amino acid identity with TxP-I. Larvae infected with a recombinant baculovirus expressing tox21A are paralyzed during infection in a manner similar to larvae infected with tox34-expressing recombinants. The tox21A cDNA may represent a duplicated and diverged copy of the TxP-I gene. PMID- 8470136 TI - Neutralizing capacity of murine sera induced by different antigens of scorpion venom. AB - Approximately 700 people die in Mexico each year from scorpion stings. The only useful therapy available is antiserum obtained from horses immunized with macerates of venomous gland from scorpions of the genus Centruroides. We report the results of experiments conducted with mice and rats in order to evaluate the relevant components of the venom from Centruroides noxius in the induction of a protective response against scorpion envenomation, either in vivo or in vitro. Gland macerates of whole telsons (stinger), soluble venom extracted by electrical stimulation, toxic fractions from gel filtration on Sephadex G-50 and highly purified toxin 2 from this scorpion venom were all used to produce hyperimmune mice and rats, which were challenged in vivo with the equivalent of the lethal dose 50% (LD50) of soluble venom, or their sera were prepared for in vitro neutralization experiments using non-immunized animals. The maximum neutralizing capacity (100%) was obtained when soluble venom was used as antigen, while purified toxin 2 produces 80% survival in vivo. The neutralizing capacity of murine antisera evaluated in vitro was: sera antifraction II > antitoxin 2 > antitotal venom > anti-gland macerates of whole telsons. Two additional aspects were further investigated in the present work. One is the demonstration by immunoblotting that proteins corresponding to the electrophoretic mobility of toxins known to block sodium channels are highly immunodominant in this venom. Second, there is a strong cross-reactivity of antisera produced with Centruroides noxius when assayed against venoms from other dangerous species of Centruroides scorpions from Mexico, but not against the Israeli scorpion Leiurus quinquestriatus. Finally, the immunodominance of toxic fractions in the immune response was observed either with immunization using Freund's adjuvant or by means of adsorption to nitrocellulose membranes. This latter vehicle was shown to be an excellent detoxifying agent, without changing the immunogenicity of the toxins, as might occur with chemical treatment of these neurotoxic peptides. PMID- 8470137 TI - Pharmacokinetics of cytotoxin from Chinese cobra (Naja naja atra) venom. AB - The pharmacokinetics of cytotoxin from Chinese cobra (Naja naja atra) venom was studied in rabbits after i.v. and i.m. injection of 0.2 and 0.5 mg.kg-1, respectively. The plasma levels of the cytotoxin were analysed by a biotin-avidin enzyme-linked immunosorbent assay. The plasma concentration-time course after i.v. administration fitted a two-compartment open model. The half-life (mean +/- S.D.) of the alpha-phase was 5.8 +/- 0.6 min and that of the beta-phase 3.5 +/- 0.2 hr. Apparent volume of distribution was 1.7 +/- 0.3 litres.kg-1, and clearance was 5.6 +/- 1.4 ml.min-1. A rapid absorption was observed after i.m. injection with peak plasma level of 260 +/- 90 ng.ml-1 reached within 13.6 +/- 2.4 min. The absorption rate constant was 0.16 +/- 0.03 ml-1. The area under the plasma concentration-time curve was 33 +/- 15 micrograms.min.ml-1. PMID- 8470138 TI - Biological activities of fumonisins, mycotoxins from Fusarium moniliforme, in jimsonweed (Datura stramonium L.) and mammalian cell cultures. AB - Fumonisins A1, A2, B1, B2 and B3 are a series of mycotoxins produced by strains of Fusarium moniliforme. Fumonisins are hydroxylated long-chain alkylamines esterified with propanetricarboxylic acid moieties that represent approximately half the mol. wt of the toxins. The A-series fumonisins are N-acetylated, whereas the B series contains free amino groups. Hydrolytic removal of the propanetricarboxylic acid moieties from fumonisins B1 and B2 yields the corresponding aminopentols, AP1 and AP2, respectively. These compounds were tested for toxicity on widely differing bioassay systems, representing plant and animal systems. The plant bioassay system employed jimsonweed (Datura stramonium L.) leaves and leaf discs in which toxicity was detected as electrolyte leakage, photobleaching and quantitation of chlorophyll reduction. The animal bioassay system employed cultured mammalian cell lines in which toxicity was detected as inhibition of cell proliferation. Fumonisins B1, B2 and B3 at 50 micrograms/ml or less were effective toxins after exposure periods greater than 24 hr in all plant and animal bioassay systems examined, except 3T3 mouse fibroblasts, whereas fumonisins A1 and A2 exhibited little or no activity. However, the hydrolytic degradation products AP1 and AP2 exhibited toxicity similar to or greater than B series fumonisins in all test systems, including substantial toxicity to 3T3 mouse fibroblasts. PMID- 8470139 TI - Isolation and purification of AAL-toxin from Alternaria alternata grown on rice. AB - An isolation and purification procedure is described for AAL-toxin, a secondary metabolite produced by Alternaria alternata. The method involves growth of the fungus on rice media, extraction with chloroform followed by methanol: water from fungus-infested rice, and purification of the aqueous layer that contains AAL toxin by using chromatography methods. The AAL-toxin was of type A, and white in color, and its purity was > or = 95% with mol. wt 522 (M + 1). PMID- 8470140 TI - A comparative study of the biological properties of venoms from juvenile and adult inland taipan (Oxyuranus microlepidotus) snake venoms. AB - The biological properties of adult and juvenile inland taipan (Oxyuranus microlepidotus) snake venoms were examined. The enzymatic activities, intravenous median lethal dose and procoagulant activity of the juvenile venom samples were not significantly different from those of the adult venom samples. Also, the juvenile and adult venoms exhibited similar electrophoretic patterns, indicating that they possessed similar protein composition. PMID- 8470141 TI - Endocytic components: identification and characterization. PMID- 8470142 TI - Toward a biochemical definition of the endosomal compartment. Studies using free flow electrophoresis. PMID- 8470143 TI - Analytical subcellular fractionation of endosomal compartments in rat hepatocytes. PMID- 8470144 TI - Intravascular volume regulation in cirrhotic patients with functional renal failure. AB - Central volume expansion is an important component of treating renal dysfunction associated with advanced chronic liver disease. Experiments using HWI in these patients emphasize the importance of increasing central vascular filling as a way to normalize renal function through multiple physiologic mechanisms. However, the desired improvement in renal function is not always obtained with HWI, especially in patients with greater degrees of hepatic dysfunction, central volume depletion, and activation of neurohumoral support systems. This may, in part, be related to reflexive decreases in systemic vascular resistance during immersion. The development of techniques to expand central arterial volume while maintaining systemic vascular resistance and mean arterial pressure may add to the beneficial effects on renal function in cirrhotics. Pneumatic compression of the lower extremities may be one way of achieving the desired circulatory effects. Adjunctive therapy with splanchnic vasoconstrictors may be necessary in patients with marked vasodilation but they often have undesirable intrarenal actions. PMID- 8470145 TI - Pathogenesis of hepatorenal syndrome. PMID- 8470146 TI - Renal failure in cirrhosis and liver transplantation. PMID- 8470147 TI - Dialysis in liver failure and liver transplantation. PMID- 8470148 TI - Circulation in liver disease. PMID- 8470149 TI - Hepatopulmonary syndrome. PMID- 8470150 TI - Kidney function following orthotopic liver transplantation and its relationship to arterial hypertension. PMID- 8470151 TI - Neurological disorders and intraoperative factors in liver transplantation. PMID- 8470152 TI - Prophylactic recombinant hepatitis B vaccine in patients undergoing orthotopic liver transplantation. PMID- 8470153 TI - Nonspecific cholestatic syndrome in liver transplantation: successful symptomatic treatment by plasma exchange. PMID- 8470154 TI - Hepatitis B virus replication patterns after orthotopic liver transplantation: de novo versus recurrent infection. PMID- 8470155 TI - Maintenance immunosuppression with prednisone and RS-61443 alone following liver transplantation. PMID- 8470156 TI - Outcome of patients requiring hemodialysis after liver transplantation. PMID- 8470157 TI - Transjugular intrahepatic portacaval stent shunts in patients with renal insufficiency. PMID- 8470158 TI - Renin-angiotensin-aldosterone system and arterial hypertension following orthotopic liver transplantation. PMID- 8470159 TI - Child-Pugh score and liver transplantation. PMID- 8470160 TI - Neuropsychiatric complications after liver transplantation: a single center experience. PMID- 8470161 TI - Relationship between cerebral perfusion pressure and systemic hemodynamics in fulminant hepatic failure. PMID- 8470162 TI - Serum amino acids following human orthotopic liver transplantation. AB - Our findings indicate that serum amino acid changes after OLT are complex and influenced by multiple factors including sepsis and use of parenteral hyperalimentation with exogenous amino acids. Additional factors which may influence the rate of normalization of amino acids after OLT include the presence of malnutrition (frequently observed before OLT) and the extent of pretransplant portal-systemic shunting. Our results demonstrate that the presence of septic complications and the use of CPN are important determinants of the postoperative levels of several amino acids, including the BCAA/AAA ratio. Our logistic regression model using the BCAA/AAA ratio predicted the occurrence of sepsis after OLT 77% of the time. Prospective assessment and validation of this model is under way. PMID- 8470163 TI - Soluble interleukin-2 receptor levels in pediatric liver transplant recipients. PMID- 8470164 TI - Somatic muscle catabolism is accelerated after liver transplantation. PMID- 8470165 TI - Reversibility of the hepatopulmonary syndrome by orthotopic liver transplantation. PMID- 8470166 TI - Reversibility of pulmonary hypertension after liver transplantation: a case report. PMID- 8470167 TI - Dynamic aspects of albumin and other plasma proteins after liver transplantation from analbuminemic to normal rats. PMID- 8470168 TI - Effect of cyclosporine on the distribution of macrophage phenotypes in the rat hepatic allograft. PMID- 8470169 TI - Transcranial Doppler: monitoring of cerebral blood flow velocity during liver transplantation. PMID- 8470170 TI - Comparison of shunt fractions pre- and post-liver transplantation. PMID- 8470171 TI - Prognostic value of the APACHE II, SAPS, and TISS indexes in short-term survival of liver transplant patients. PMID- 8470172 TI - Circulating heparin during liver transplantation. PMID- 8470173 TI - Gastric mucosal pH predicts major morbidity following orthotopic liver transplantation. PMID- 8470174 TI - Hepatic oxygen supply and uptake during anesthesia for orthotopic liver transplantation. PMID- 8470175 TI - Platelet activating factor mediates systemic circulatory collapse after temporary hepatic inflow occlusion. PMID- 8470176 TI - Reperfusion during orthotopic liver transplantation: analysis of right ventricular dynamics. PMID- 8470177 TI - Intra-allograft production and systemic release of tumor necrosis factor-alpha: detection upon reperfusion. PMID- 8470178 TI - How helpful is intracranial pressure monitoring in patients with acute hepatic failure? PMID- 8470179 TI - Analysis of two thrombokinetic measurements (thrombelastograph and Sonoclot) during liver transplantation. PMID- 8470180 TI - In vitro effects of DDAVP during liver transplantation. PMID- 8470181 TI - Blood usage in a newly organized liver transplant program. PMID- 8470182 TI - Is the ratio of venovenous bypass flow to cardiac output important during orthotopic liver transplantation? PMID- 8470183 TI - Is it important to measure magnesium concentrations during and immediately after liver transplantation? PMID- 8470184 TI - Endotoxin and tumor necrosis factor levels and hemodynamics during human liver transplantation. PMID- 8470185 TI - Vasoactive intestinal peptide and calcitonin gene-related peptide levels and hemodynamics during human liver transplantation. PMID- 8470186 TI - Transesophageal echocardiographic evaluation of left ventricular function during orthotopic liver transplantation. PMID- 8470187 TI - Effectiveness of rapid infusion and Bair Hugger systems in maintaining normothermia during orthotopic liver transplantation. PMID- 8470188 TI - Glucose/insulin to adjust potassium levels during orthotopic liver transplantation. PMID- 8470189 TI - Incidence and risk factors of early acute renal failure in liver transplant patients. PMID- 8470190 TI - Blood product transfusion therapy after liver transplantation: comparison of the thromboelastogram and conventional coagulation studies. PMID- 8470191 TI - Hyperdynamic circulatory state after liver transplantation. AB - HCS is common pre-LT (69% of our patients) and frequently develops in NHCS patients during LT. There is a trend toward normalization of HCS after LT. Despite the increased requirement for postoperative blood transfusion in those patients with HCS, it may be prudent to avoid treatment of HCS with cardiodepressants and await its spontaneous reversal. PMID- 8470192 TI - Successful liver transplantation in patients with mild to moderate pulmonary hypertension. PMID- 8470193 TI - Intracranial pressure monitoring during liver transplant without venovenous bypass for fulminant hepatic failure. PMID- 8470194 TI - Right ejection fraction and maximum elasticity are sensitive measurements of right ventricular function during liver transplantation. PMID- 8470195 TI - Pre- and intraoperative differences between patients with chronic liver disease and fulminant hepatic failure undergoing liver transplant. PMID- 8470196 TI - Cyclosporine, isoflurane, and oxygenation effects on energy balance in isolated hepatocytes. PMID- 8470197 TI - Hemodynamic changes during adult liver transplantation with partial vena cava clamping. PMID- 8470198 TI - Altered hepatic function by atracurium or its breakdown products. PMID- 8470199 TI - Use of Swan-Ganz catheter for monitoring right ventricular ejection fraction during liver transplantation. PMID- 8470200 TI - High-dose laudanosine enhances liver cell activity and bile flow during reperfusion of the liver. PMID- 8470201 TI - Titrating the preload by using the rapid infusion system: use of echocardiography during orthotopic liver transplantation. PMID- 8470202 TI - Prostaglandin metabolism and hemodynamic alterations during human liver transplantation. PMID- 8470203 TI - Hemodynamic monitoring during orthotopic liver transplantation. PMID- 8470204 TI - Venovenous bypass vs no bypass in orthotopic liver transplantation: metabolic values during reperfusion. PMID- 8470205 TI - Liver transplantation for fulminant liver failure: a dilemma in therapeutic approach. PMID- 8470206 TI - Quantification of liver damage and prediction of 1-year survival after liver transplantation by a multifactorial "recovery score". PMID- 8470207 TI - Incidence and outcome of OKT3 treatment for early steroid-resistant rejection following hepatic transplantation. PMID- 8470208 TI - Fulminant hepatic failure, hepatorenal syndrome, and necrotizing pancreatitis after minocycline hepatotoxicity. PMID- 8470209 TI - Successful liver/kidney transplantation across ABO incompatibility. PMID- 8470210 TI - Use of water-soluble liquid vitamin E to enhance cyclosporine absorption in children after liver transplant. PMID- 8470211 TI - Activated cytokine pattern in hepatorenal syndrome: fall in levels after successful orthotopic liver transplantation. PMID- 8470212 TI - Use of an absorbable suture material in vascular anastomoses in pediatric liver transplantation. PMID- 8470213 TI - Protective effect of polyethylene glycol-conjugated superoxide dismutase for cold ischemia-reperfusion damage in isolated pig livers. PMID- 8470214 TI - Experiences with histidine-tryptophan-ketoglutarate-perfused organs in clinical liver transplantation. PMID- 8470215 TI - Bilirubin secretion as an early indicator of patient survival following orthotopic liver transplantation. PMID- 8470216 TI - Orthotopic liver transplantation and renal function; outcome of hepatorenal syndrome and trial of verapamil for renal protection in nonhepatorenal syndrome. PMID- 8470217 TI - Suppression of hepatic allograft rejection in the rat by mitomycin C-treated donor splenocytes: the distribution of donor class I-positive cells in the recipient. PMID- 8470218 TI - Cannulation of the inferior mesenteric vein for veno-venous bypass in human liver transplantation: a reliable procedure? PMID- 8470219 TI - Living donor hepatectomy in partial liver transplantation: surgical technique and results. PMID- 8470220 TI - Influence of warm ischemia on cold-stored, University of Wisconsin solution protected rat liver: investigation by 1H-nuclear magnetic resonance relaxometry. PMID- 8470221 TI - Liver transplantation for chronic hepatitis B in Asian males. PMID- 8470222 TI - Association between preservation injury and early rejection in clinical liver transplantation: fact or myth? PMID- 8470223 TI - Influence of cyclosporine on liver regeneration after orthotopic reduced-size hepatic transplantation in the rat. PMID- 8470224 TI - Orthotopic liver transplantation for alpha-1-antitrypsin deficiency in identical twins. PMID- 8470225 TI - Liver transplantation in alcoholics: assessment of psychological health and work activity. PMID- 8470227 TI - Hepatic retransplantation in children. PMID- 8470226 TI - Indocyanine green clearance in the evaluation of donor livers. PMID- 8470228 TI - Comparison of perioperative morbidity following primary liver transplantation and liver retransplantation. PMID- 8470229 TI - Roux-en-Y anastomotic bleeding following orthotopic liver transplantation: experience in our first 300 patients. PMID- 8470230 TI - Heterogeneous effect of liver transplantation on the granuloma-enhancing factor of primary biliary cirrhosis. PMID- 8470231 TI - Hemodynamics in acute porcine heterotopic liver transplantation: effects of graft reduction. PMID- 8470232 TI - Auxiliary partial liver transplantation in pigs with acute ischemic liver failure. PMID- 8470233 TI - Parasympathetic tone alterations during rat hepatectomy: a cause of preservation/harvest injury? PMID- 8470234 TI - Quadruple induction immunosuppression after liver transplantation with interleukin-2 receptor antibody (BT 563) is equally effective and better tolerated than antithymocyte globulin induction therapy. PMID- 8470236 TI - Demonstration of biochemical function by extracorporeal xenohepatocytes in an anhepatic animal model. PMID- 8470235 TI - Experience of en bloc technique for abdominal organ harvesting for experimental transplantation. PMID- 8470237 TI - Effect of surgical and spontaneous portasystemic shunts on liver transplantation. PMID- 8470238 TI - Cyclosporine vs OKT3 prophylaxis after orthotopic liver transplantation. PMID- 8470239 TI - Successful prolonged correction of an inborn metabolic defect by heterotopic auxiliary liver transplantation in a dog model. PMID- 8470240 TI - Influence of additional warm ischemia on rat hepatic energy metabolism: a comparison of University of Wisconsin and HTK protection. PMID- 8470241 TI - ABO incompatible liver transplantation in children: a prospective approach. PMID- 8470242 TI - Possible role of hepatic nonparenchymal cells in liver allograft rejection. PMID- 8470243 TI - Ex vivo perfusion of livers with anti-class II antibody and acute rejection in canine liver transplantation. PMID- 8470244 TI - Identification of donor and recipient risk factors associated with nonanastomotic biliary strictures in human hepatic allografts. PMID- 8470245 TI - Quadruple-drug therapy with antithymocyte globulin in the early postoperative period after liver transplantation. PMID- 8470246 TI - Routine monitoring of liver grafts by transplant aspiration cytology: clinical experience with 3000 TACs. PMID- 8470247 TI - Acute portal vein thrombosis: a cause of rapid deterioration of liver function, treatable by thrombectomy and transplantation. PMID- 8470248 TI - Predictors of primary nonfunction: is donor liver fat content important? PMID- 8470249 TI - Hepatocyte regeneration during liver allograft rejection in the rat. PMID- 8470250 TI - Imprint cytology in liver transplantation: diagnosis of rejection. PMID- 8470251 TI - New preparation method for bile cytology in liver transplantation: diagnosis of rejection. PMID- 8470252 TI - Role of cytochrome P-450 in modulating cyclosporine levels in transplant patients. PMID- 8470253 TI - N-acetylcysteine attenuates cold ischemia/reperfusion injury in the isolated perfused rat liver. PMID- 8470254 TI - Impact of liver transplantation on the reversal of hypersplenism. PMID- 8470255 TI - Role of T-cell subsets in rat liver allograft rejection. PMID- 8470256 TI - Must I be my brother's keeper? Ethical issues in the use of living donors as sources of liver and other solid organs. PMID- 8470257 TI - Coagulation and liver transplantation. AB - In summary, both a thorough understanding of the pathogenesis of coagulopathies and an understanding of the proper replacement and pharmacologic therapies based on TEG monitoring of coagulability are essential in the management of coagulation. As stated by Starzl, "Now cautious correction of coagulation defects is an integral part of liver transplantation, greatly diminishing the hemorrhages of nightmare proportions that were common." PMID- 8470258 TI - Hepatitis C and B in liver transplantation. AB - Hepatitis B recurrence remains a major problem facing liver transplantation programs. The risk of infection varies depending upon the HBV load. High doses of HBIg may reduce the risk of occurrence but it remains expensive. Finally, apparently new infections may occur posttransplantation, which may have been transmitted by organs or blood from HBsAg (-), HBcAb (+) donors, or may reflect reactivation of latent infections in patients who were HBsAg (-). HCV infections are common in patients undergoing liver transplantation, and HCV infection recurs in > 90% of patients; however, recurrent hepatitis C occurs in less than half of these patients. HCV is not an important cause of fulminant non-A, non-B hepatitis, but appears to be the most common cause of posttransplant hepatitis. So what is in the future? For hepatitis B, we still believe the efficacy of HBIg, and in which patients with hepatitis B HBIg should be used, remains to be defined. The effects of antivirals on posttransplant hepatitis B, as well as in prevention of HBV recurrence, also remain to be determined. In the United States, insurance companies are likely to play an important role in determining the future of transplantation for hepatitis B. Medicare recently excluded patients who were HBsAg (+) from coverage for liver transplantation, and a number of private insurers have subsequently followed suit. For HCV, newer screening tests for the virus are likely to decrease the rate of HCV acquisition following liver transplantation, from the current 35% incidence of HCV acquisition. The impact of antiviral treatment on posttransplant hepatitis remains to be determined and deserves study. Finally, the development of regimens that might allow prevention of recurrent HCV infections in patients undergoing liver transplantation also should be a matter of future study. PMID- 8470259 TI - Update on preservation of liver grafts. PMID- 8470260 TI - Liver disease and pulmonary hypertension. PMID- 8470261 TI - Diagnostic criteria for chronic rejection/accelerated graft atherosclerosis in heart and kidney transplants: joint proposal from the Fourth Alexis Carrel Conference on Chronic Rejection and Accelerated Arteriosclerosis in Transplanted Organs. PMID- 8470262 TI - Chronic rejection of organ allografts: magnitude of the problem. PMID- 8470263 TI - Diagnostic criteria of chronic rejection in transplanted hearts. PMID- 8470264 TI - Morphological criteria of chronic rejection: differential diagnosis, including cyclosporine nephropathy. PMID- 8470265 TI - Transforming growth factor-beta and organ transplantation. PMID- 8470266 TI - Atherosclerosis: current understanding of mechanisms and future strategies in therapy. AB - The lesions of atherosclerosis represent a protective, inflammatory fibroproliferative response against the different agents that can cause the disease. If the injury continues chronically over a sufficiently long period of time, and if opportunity is not given for restitution of normal architecture in the artery wall, lesions may progress to a point at which clinical sequelae develop. On the other hand, as demonstrated by Brown et al, Kane et al, and Blankenhorn et al, the advanced lesions of atherosclerosis can be shown to regress. A quantitative, statistical analysis of angiograms in patients who are aggressively treated with lipid-lowering agents, such as HMGCoA reductase inhibitors has clearly shown this to be the case. Thus, it is entirely conceivable that this chronic, excessive, inflammatory, and fibroproliferative response can be reversed, given sufficient opportunity for the factors that have led to the endothelial and arterial wall injury causing these events to be taken into hand and modified. PMID- 8470267 TI - Role of hyaluronan in chronic and acutely rejecting kidneys. PMID- 8470269 TI - Endothelial integrity and injury in atherogenesis. PMID- 8470268 TI - Lymphocyte adhesion and cellular immune reactions in chronic rejection and graft arteriosclerosis. PMID- 8470270 TI - Endothelium-derived relaxing factor and the vascular role of guanidino compounds. PMID- 8470271 TI - Lipid oxidation, vascular inflammation, and coronary atherosclerosis. PMID- 8470272 TI - Hyperlipoproteinemia in renal transplant recipients: is there a linkage with chronic vascular rejection? PMID- 8470273 TI - Leukocyte-endothelium interaction as a target for antiatherogenic strategies in allograft transplantation. PMID- 8470274 TI - Pathophysiology of allograft arteriosclerosis. PMID- 8470275 TI - Cardiac graft arteriosclerosis in the rat. PMID- 8470276 TI - Possible in vivo effect and clinical utility of platelet-derived growth factor and PDGF antagonists. PMID- 8470277 TI - Animal models of chronic heart and kidney allograft rejection. PMID- 8470278 TI - Chronic rejection and suboptimal immunosuppression. PMID- 8470279 TI - Controlled prospective study of treatment for chronic rejection after kidney transplantation by thromboxane synthetase inhibitor. PMID- 8470280 TI - Use of NSAIDs in kidney transplantation. PMID- 8470281 TI - Use of dietary fish oils in renal allograft recipients with chronic vascular rejection. PMID- 8470282 TI - Inhibition of graft arteriosclerosis by modulation of the inflammatory response. PMID- 8470284 TI - Effect of acute damage from acute rejection and ischemia on long-term renal allograft histology. PMID- 8470283 TI - Prolonged renal allograft survival in chronic rejection by conversion to triple therapy. PMID- 8470285 TI - Evaluation of animal models of chronic vascular rejection. PMID- 8470286 TI - Chronic rejection of organ allografts may arise from injuries sustained in recurring foci of acute rejection that resolve spontaneously. PMID- 8470287 TI - Mesangial immunoglobulin A deposition and focal glomerulosclerosis in a renal transplant patient with nephrotic syndrome--Berger's disease alone or superimposition of focal glomerulosclerosis? PMID- 8470288 TI - Estimated number of diabetic recipients of pancreas transplant in Japan. PMID- 8470289 TI - Successful 24-hour preservation of canine lungs for allotransplantation using verapamil. PMID- 8470290 TI - Murine skin allograft histocompatibility combinations susceptible to induction of tolerance by intraportal inoculation of allogeneic spleen cells. PMID- 8470291 TI - Kidney transplantation in Cyprus. PMID- 8470292 TI - Donor-transmitted non-Hodgkin's lymphoma after renal transplantation--a case report. PMID- 8470293 TI - Appearance of a de novo renal tubulopapillary adenoma in an allograft recipient. PMID- 8470294 TI - Interaction between glipizide and cyclosporine: report of two cases. PMID- 8470295 TI - Tumor necrosis factor and interleukin-6 in cerebrospinal fluid of a patient with recurrent adverse central nervous system events following OKT3. PMID- 8470296 TI - Soluble CD23 and interleukin-2 receptor levels in renal allograft recipients. PMID- 8470297 TI - Effect of liver and kidney preservation solutions on vascular viability: studies on contraction and relaxation of rat aorta in vitro. PMID- 8470299 TI - Survey of sickle disease in Kenya. AB - In Kenya and most of Eastern Africa, sickle haemoglobin (HbS) is the pre-dominant beta-globin chain abnormality; homozygous sickle cell disease, (SCA), is the predominant form of sickle cell disease. Although the prevalence of sickle cell trait (SCT) in Kenya was known, the magnitude of SCA was yet to be established. We performed a national survey in all hospitals from November 1987 to May 1990 and found 3605 cases with SCA. Age was recorded for 2821 patients. Seventy-seven per cent of these patients were below the age of fifteen. The oldest patient was a 50-year-old female. The paediatric to adult ratio was 3:1. More than 80% of the patients were of Luo or Luhya ethnic origin (Luo 58.4%, Luhya 23.9%). There was a discrepancy between SCT rate (SCTr) and the percentage distribution of SCA patients per province. The Kambes of the Mijikenda group in the Coast Province with the highest SCTr (35%) constituted only 8.5%, but the Luos with a SCTr of 28%, 58% of the total SCA patient population in Kenya. We found reports of SCA in the Somali and Turkana, in whom no SCT had been found previously. PMID- 8470298 TI - Prospective in-vivo study of chloroquine resistance of Plasmodium falciparum in Zambian under-fives. AB - Zambian under-fives with malaria were selected on a positive thick blood smear for Plasmodium falciparum of at least 1000 parasites/microliter on the day of admission. During a chloroquine course, daily follow-up of parasitaemia was performed. Bloodsamples were taken on day 0 and day 3 to measure chloroquine levels before admission and after treatment. Eighty four patients were evaluated in this study. Forty eight patients did not meet all criteria. Thirty six patients met all criteria, of which 16 (44.5%) patients were infected with sensitive strains (S) and 20 (55.5%) with resistant strains (R) of P.falciparum. PMID- 8470300 TI - The approach to the leprosy problem in the past in Indonesia. A historical review of leprosy control activities in Indonesia during the last centuries. AB - Due to the severe disabilities leprosy has always been a disease which appealed to the imagination. In bygone centuries cause and treatment were unknown and the fear to be infected was enormous. In Indonesia medical officers struggled with the problem. As early as the 17th century the disease was described in detail by Ten Rhijne. In the 19th century leprosy was considered hereditary. After the discovery of the leprosy bacillus by Hansen in 1873, confusion continued as the bacillus could not be cultivated. Many therapies were tried, but with no result. At first patients were isolated in leprosaria, later on a more humane system of house-isolation was introduced. Since 1932 Indonesian medical officers have played a prominent part in research and the determination of the future approach to the problem. Seen against the background of our present knowledge about the disease, it is interesting to follow the struggle against leprosy in the past. PMID- 8470301 TI - Oesophageal diseases in Sudan, diagnosed by fibreoptic endoscopy. AB - Fibreoptic endoscopy was performed on 5,086 consecutive patients with upper gastrointestinal tract disease (UGITD) symptoms, at two endoscopy centres in Khartoum over five years. Oesophageal disease was diagnosed in 559 patients (11%) comprising (20.5%) of all the positive findings. In 46% of all the endoscopies no abnormality was detected. The commonest oesophageal disease was varices occurring in 186 patients (3.7%) of the 5,086 endoscopies with a mean age of 33.5 +/- 12 and a male/female ratio of 3.4:1. Hiatus hernia occurred in 124 patients (2.4%) with a male/female ratio of 1.6:1, oesophagitis in 115 patients (2.3%) with a male/female ratio of 2:1. Carcinoma of the oesophagus was diagnosed in 108 patients (2.1%), with a mean age of 56 +/- 14 years and a male/female ratio of 1.4:1. Achalasia of the oesophagus occurred in 20 patients (0.4%), Mallory Weiss syndrome in 4 patients (0.08%) and benign strictures in 2 patients (0.04%). PMID- 8470302 TI - Esophageal cancer in Qatar. AB - There were 41 cases of esophageal cancer over a 7 years period in the State of Qatar. Qataris accounted for 30 (73.17%) of these cases while representing about 38% of the entire population. Also there is a slight preponderance of female cases especially among Qataris. Nutritional factors, dietary preferences, environmental factors, social status and habits as well as genetic factors may constitute important etiologic factors in the genesis of esophageal cancer in Qatar. PMID- 8470303 TI - Differences in presentation of Hodgkin's disease in Sudan and Western countries. AB - A retrospective study was performed dealing with clinical and histopathological aspects of Hodgkin's disease in patients presenting to the Radiation and Isotopes Centre of Khartoum (RICK) during the period from January 1984 to January 1989. A total of 105 patients were studied; this number accounted for 30.6% of all lymphoma patients and 2.0% of all cancers seen at RICK during the same period. The median age was 30 yrs, and the majority of patients were within two age groups, above 25 yrs and above 50 yrs, demonstrating a bimodal pattern. Males were commonly affected and this was more marked in children (M:F = 4.7:1.0). Two striking differences are observed between this study and those from the western world. The first was the high incidence of late clinical stages (III,IV) (70%) in this series despite the moderate duration of symptoms. The second was predominance of mixed cellularity and lymphocytic predominant sub-groups (65%) compared to reports from the western world. A possibility of a chronic stimulatory process of the lymphatic system is raised. The high incidence of late clinical stages on presentation with favourable histological types needs more work. PMID- 8470304 TI - Assault, a burden for a rural hospital in Lesotho. AB - A retrospective study among adult inpatients revealed the prevalence and characteristics of assault trauma in a district hospital in Southern Lesotho. A comparison with non-assault trauma and non-trauma inpatients highlights the burden of this problem on the available resources. In one year 20.6% of all admissions of adult men were victims of purposely inflicted injuries while 11.4% were due to other (accidental) trauma. For women these figures were 5.8% and 10.3% respectively. Post mortem examination at the hospital allowed an estimation of the homicide rate of 40.9 per 100,000 in the catchment area of the hospital. The age group of 20 to 29 years constitute 40% of the assault patients. Knives and sticks cause most damage and the head receives the more serious blows in 67% of the cases. The group of assault victims needed considerably more care than other patients. PMID- 8470305 TI - Haemangioma of the vallecula causing acute upper airway obstruction in a 6 1/2 week old Nigerian infant with strawberry naevus. AB - Expectant management remains the treatment of choice in isolated capillary haemangiomata, but active intervention is indicated when they constitute a threat to vital functions. We report a 6 1/2 week old Nigerian infant with acute stridor and unilateral haemangiomata involving the parieto-temporal scalp, forehead and periorbital skin. Direct laryngoscopy showed an ipsilateral haemangioma of the vallecula and adjoining structures. Extensive periorbital lesions suggested a risk of subsequent occlusive amblyopia. Systemic corticosteroids were initiated with good response. The possible diagnostic considerations and therapeutic options are discussed. When active management is indicated for infantile capillary haemangiomata in resource-poor countries, we emphasise the wisdom of a supervised short course of systemic steroids. PMID- 8470306 TI - Parathyroid adenoma in northern Nigeria. AB - A middle-aged farmer and a female student presented with osteitis fibrosa cystica with nephrocalcinosis in the former and nephrolithiasis in the latter due to primary hyperparathyroidism. Hypercalcaemia was present in both cases and neck exploration revealed a large solitary parathyroid adenoma which was excised. Because primary hyperparathyroidism is less common in tropical countries doctors may be less familiar with the early manifestations of the disease. The number of patients thus undiagnosed and untreated is unknown. PMID- 8470307 TI - Stress fracture of the patella in a palmwine tapper. AB - Stress fracture of the patella in a twenty-nine-year-old palmwine tapper is reported. The fracture occurred during a busy tapping day which was his first working day after a ten-day sick off for a febrile illness and presentation was delayed for six weeks. Initial diagnosis was pathological fracture, but X-ray examination and histology of the biopsy from the fracture site did not suggest any associated disease. The pathomechanics of palmwine tapping is very similar to jumping (parachute) which is the usual cause of this fracture in developed countries. PMID- 8470308 TI - Chronic plantar ulcer of a leprosy patient treated by fasciocutaneous instep flap transfer. Preliminary result. AB - A case of chronic ulceration of the foot (chronicity about 15 years) was treated with fasciocutaneous instep flap transfer. The ulcer was on the heel. Healing was fast (about 40 days post-operatively. Duration for conventional method is about 6 months) and after 12 months of ambulation no recurrence was noticed. The female patient with only one lower limb (the other already amputated) now goes about smilingly selling her wares. However, the footwear for the patient had to be further modified. PMID- 8470309 TI - Multiple high dose vitamin A supplementation. A report on five cases. AB - Vitamin A toxicity is a concern among health care providers, especially when present recommendations for vitamin A may result in multiple dosing during a short period of time. We observed no vitamin A toxicity in 5 children who received multiple high doses of vitamin A. These 8-month to 5-year-old children were part of a community trial of vitamin A during acute measles, and were being treated at a local hospital for severe acute respiratory infection, malaria, and/or diarrhoea. One 12-month-old who received 1,612,500 I.U. within a period of three weeks showed elevated serum retinol (3.42 mumol/l), but none of the five showed signs of toxicity. These cases illustrate the confusion surrounding the correct use of vitamin A for infants and children with multiple morbid conditions. A plea is made to report similar situations since clinical trials are unethical. PMID- 8470310 TI - Cholelithiasis in children with homozygous sickle cell anaemia in northern Nigeria. AB - The prevalence of gall stones was studied prospectively by abdominal ultrasound examination in 65 consecutive children with sickle cell anaemia (SCA) aged 5-13 years, 35 males and 30 females, in Jos, northern Nigeria. The prevalence of cholelithiasis was 4.6%. This rate was similar to previous studies from southern Nigeria and higher than that reported in American children with SCA. The different dietary habits of children in southern and northern Nigeria appear not to play any role in the prevalence rate. None of the children followed up for more than 12 months had upper quadrant abdominal pain that warranted surgery. PMID- 8470311 TI - Malaria chemosuppression in pregnancy. I. The effect of chemosuppressive drugs on maternal parasitaemia. AB - A randomized prophylactic drug trial was conducted in a malaria holoendemic area, in the Muheza District of Tanzania. Of 327 pregnant women, 124 received proguanil (PROG), 113 chloroquine (CQ), 90 the proguanil and chloroquine combination (CQ+PROG). Prophylaxis was supervised. Chemosuppressive efficacy was measured through the incidence of malaria breakthrough parasitaemias and clinical episodes. Groups were comparable by age, parity, residential area, and enrollment gestational age. Compliance and drug bio-availability was good. The median breakthrough time of the first parasitaemia episode for primigravidae (PG) and multigravidae (MG) was significantly shorter for the CQ group (PG = 56, MG = 78 days) than in the PROG (PG = 97, MG = 112 days) and the CQ+PROG (PG = 138, MG = 140 days) groups. 56% of the CQ group experienced 2 or more clinical episodes compared to 19% (PROG) and 10% (CQ+PROG). PROG and CQ+PROG did not differ significantly. Parasite densities and in vitro tests suggested that CQ selected for more and highly resistant strain(s). Proguanil is suitable for prophylaxis. However, proguanil resistance should be monitored as well as controlled drug distribution and usage. Malaria control strategies other than chemoprophylaxis should be investigated. PMID- 8470312 TI - Diagnosis and treatment of 409 patients with prostatitis syndromes. AB - We reviewed 409 patients who had prostatitis syndromes during the period 1985 1991. Urine analysis, x-ray film of abdomen, and sonograms of the kidneys did not contribute to the diagnosis of prostatitis. In 22 percent of the urine samples, slight-to-moderate atypia was seen in urine cytology but no malignancy was found. Uroflowmetry data were abnormal for 30 percent of the patients, and thus uroflowmetry may contribute to treatment selection of patients who may gain from specific drugs such as the newly developed alpha-1 receptor blocking agents. Positive bacteria cultures were found in 10.4 percent of the prostatic fluid cultures and in 14.3 percent of cultures of the urethra. Ureaplasma urealyticum was seen in 19.6 percent of the prostatic fluid cultures and in 32 percent of cultures of the urethra. Prostatic fluid cultures did not give additional information, and the outcome of semen cultures showed a poor correlation with urethra or prostatic fluid cultures. In this series, the most advocated treatment remains the antibiotic treatment (75% of patients) bringing relief of complaints in 35.6 percent of the patients and cure in 23.8 percent. However, similar results were found if no antibiotics were administered (relief of complaints in 31.6% and cure in 30.5%) and more than one course of antibiotics did not improve these results. Consequently, we advocate the use of specific antibiotics only when the causative bacterial agent has been identified. PMID- 8470313 TI - Unilateral nerve-sparing radical prostatectomy and hemicystectomy in management of prostate sarcoma. AB - A patient with sarcoma of the prostate was treated with radical prostatectomy including wide excision of the ipsilateral neurovascular bundle and hemicystectomy. Six years postoperatively he is free of disease, continent with a bladder capacity of 350 cc, voids to completion, and is potent. PMID- 8470314 TI - Reevaluation of prostate biopsy after definitive radiation therapy. AB - We have previously reported (1987) that a positive biopsy from a clinically normal prostate eighteen months or more after interstitial Iodine 125 or external beam irradiation predicted disease progression. In the present study, all biopsies were reexamined by the same pathologist (LEL) and correlated with long term patient status. Of twenty-six positive biopsy specimens, twenty-two were reconfirmed as positive and four were reassigned to a negative diagnosis (false positive = 15%). Seventy-two of seventy-seven negative specimens were available for reexamination and seventy were reconfirmed as negative while two were reassigned to a positive diagnosis (false negative = 2%). A statistically higher incidence of local and/or distant failure for patients with positive biopsy specimens compared with patients with negative biopsy specimens was again confirmed (p = < 0.001). However, there is a group of patients with a positive biopsy (17%) who remain clinically free of disease at greater than ten years of follow-up. Therefore, a positive biopsy is not an absolute indication of imminent failure. Our results demonstrate the technical difficulty and potential error in interpreting prostate biopsies after radiation therapy. Therapeutic decisions should be based not only on biopsy histology but must also weigh the patient's initial tumor stage and grade, current clinical examination, PSA level, age, and health. PMID- 8470315 TI - Mayo Clinic experience with the AS800 artificial urinary sphincter for urinary incontinence after transurethral resection of prostate or open prostatectomy. AB - The model AS800 artificial urinary sphincter was implanted in 56 patients with urinary incontinence after transurethral resection of the prostate and in 8 patients after open prostatectomy. Their ages ranged from fifty-three to eighty seven years (mean, 70 years). At presentation, 92 percent had total incontinence and 8 percent had distressing stress incontinence. Fifteen patients (23%) had had previous radiation therapy. Bulbous urethral cuffs were used in 60 (94%) patients and vesical neck cuffs in 4 (6%). Follow-up questionnaires were mailed to assess satisfaction rate and degree of continence. Continence was significantly improved in 90 percent, and 87 percent of the patients were satisfied with their sphincters. Surgical revisions were required in 14 patients (22%). Cuff compression was inadequate in 9 patients, and erosion led to revision in 3 patients. At follow-up, 3 patients had had at least one component of the AS800 removed (complete device in 2 and cuff in 1). PMID- 8470316 TI - Clinical fluorescence diagnosis of human bladder carcinoma following low-dose Photofrin injection. AB - A point-monitoring fluorescence diagnostic system based on a low-energy pulsed laser, fiber transmission optics, and an optical multichannel analyzer was used for diagnosis of patients with bladder malignancies. Twenty-four patients with bladder carcinoma, carcinoma in situ, and/or dysplasia were injected with hematoporphyrin derivative, Photofrin, 0.35 or 0.5 mg/kg body weight, forty-eight hours prior to the investigation. The ratio between the red sensitizer emission and the bluish tissue autofluorescence provided excellent demarcation between papillary tumors and normal bladder wall. Certain cases of dysplasia also could be differentiated from normal mucosa. Benign exophytic lesions such as malakoplakia appeared different from malignant tumors in fluorescence. Flat suspicious bladder mucosa such as seen in infectious diseases or after radiation therapy appeared normal on fluorescence. PMID- 8470317 TI - Role of extracorporeal shock-wave lithotripsy in treatment of urolithiasis in patients with medullary sponge kidney. AB - In an effort to identify the role of extracorporeal shock-wave lithotripsy (ESWL) in the treatment of patients with medullary sponge kidney, a retrospective review of our experience with the Dornier HM-3 lithotriptor is presented. From 1986-1991 17 patients with medullary sponge kidney ranging in age from twenty-eight to fifty-eight years received 31 treatments to a total of 24 renal units. Follow-up ranged from four to fifty-six months with an average follow-up of twenty-five months. ESWL appears to have a role in the treatment of symptomatic urolithiasis in patients with medullary sponge kidney. There may also be some benefit in treating parenchymal calcifications. No significant side effects from the treatment were noted. PMID- 8470318 TI - Volume-interval relationship of incontinence episodes in elderly inpatient men. AB - Urinary incontinence is an immense source of personal distress for older people. The characteristics of urinary incontinence in older people that contribute to understanding the pathophysiology of incontinence have not been studied extensively. In this study, 66 elderly inpatients were monitored for incontinence characteristics of incontinence volume and time interval between episodes. There was no correlation between incontinence volume and time between episodes of incontinence. This supports a previous observation that the occurrence of urinary incontinence in elderly inpatient men is not determined by the accumulated volume of urine in the bladder. PMID- 8470319 TI - Adherence to urethral catheters by bacteria causing nosocomial infections. AB - Previous clinical studies of catheters with hydrophilic coating have, in some instances, shown a delay in the onset of significant bacteriuria, while others reported no such effect. To attempt to determine reasons for these differences we decided to study bacterial adherence of bacteria obtained from nosocomial urinary tract infections associated with catheters. Almost all strains adhered to the silicone catheter and none of them adhered to the catheter with the hydrophilic surface whether incubated in urine or serum. When incubated in urine, all strains adhered to the red rubber catheters. Adherence was variable to the Teflon and elastomer surfaces. PMID- 8470320 TI - Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus like syndrome. AB - Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen. PMID- 8470321 TI - Congenital adrenal hyperplasia with testicular tumors, aggression, and gonadal failure. AB - Bilateral testicular tumors (adrenal rests) may occur in untreated or poorly controlled congenital adrenal hyperplasia. This case report describes two unique associated phenomena: (1) psychologic disturbances similar to those seen with exogenous androgen abuse, which resolved with appropriate glucocorticoid suppression of androgen over-production by this abnormal adrenal/adrenal rest tissue; and (2) testicular failure which showed a partial, delayed recovery with corticosteroid therapy. The need for a careful history and biochemical screening for all patients with bilateral testicular tumors is reinforced. PMID- 8470322 TI - Intrascrotal neurofibromas. AB - A solitary intrascrotal neurofibroma in a seventy-seven-year-old man is reported. This benign tumor of the nerve sheath arises from the Schwann cell and is rare in the external genitalia, especially in the absence of clinical and histopathologic stigmas of von Recklinghausen neurofibromatosis. The literature on intrascrotal neurofibromas is reviewed. PMID- 8470323 TI - Bladder contracture following intravesical BCG immunotherapy. AB - Intravesical BCG immunotherapy is commonly associated with irritative bladder symptoms. Bladder contracture as a result of this treatment is rare. Two cases of persistent small-capacity bladders occurring more than one year after intravesical BCG therapy are reported. PMID- 8470324 TI - Nonobstructive right circumcaval ureter associated with double inferior vena cava. AB - Computerized tomography (CT), intravenous pyelography (IVP), and ultrasound characteristics of nonobstructive right circumcaval ureter associated with double inferior vena cava in an adult is presented. The CT appearance of the retrocaval segment of the circumcaval ureter which was detected as a "thin, long line" suggests it might be a useful sign in the incidental diagnosis of the anomaly even on noncontrast-enhanced abdominal CT examination. Because of the unique IVP appearance of circumcaval ureter in this case, a new classification is presented. PMID- 8470325 TI - Neonatal regional anesthesia: alternative to general anesthesia for urologic surgery. AB - The physiologic immaturity of respiratory musculature and central respiratory control centers leads to an increased risk of apnea and respiratory complications following general anesthesia in the neonate. Regional anesthetic techniques such as spinal and caudal epidural anesthesia may obviate the need for general anesthesia and lessen the risks of perioperative morbidity. Although these techniques have been previously described in infants, the majority of reports focus on regional anesthesia during herniorrhaphy in the former, preterm infant. There is relatively little or no information concerning regional anesthesia during urologic surgery in infants, especially during the actual neonatal period (0 to 28 days). We report on three neonates (2.17 to 3.8 kg) who required anesthetic care during the neonatal period for various urologic procedures including cystoscopy, incision of a ureterocele, and vesicostomy placement. Either caudal or spinal anesthesia was successfully used in the awake infant without the need for supplemental anesthetic agents (intravenous or inhalational). The advantages, risks, and applications of regional anesthesia during urologic surgery in the neonate are reviewed. PMID- 8470326 TI - Acute scrotal swelling in Henoch-Schonlein syndrome: evaluation with testicular scanning. AB - Acute scrotal swelling may accompany Henoch-Schonlein syndrome and may be the presenting manifestation mimicking testicular torsion. Two patients with scrotal involvement were recently evaluated with nuclear imaging to assess testicular perfusion. One patient had normal perfusion, and the other had increased perfusion. Scan results allowed expectant management and avoided the need for exploratory surgery to rule out testicular torsion. PMID- 8470327 TI - Results of undiverted simple closure of 51 urethrocutaneous fistulas in boys. AB - Urethral fistulas are an inherent risk of hypospadias repair. Present-day repairs of hypospadias in which redundant skin is held to a minimum limit the applicability of skin flap advancement technique for closure. To avoid altering the cosmesis of the prior hypospadias repair, 51 urethrocutaneous fistulas were closed using a three-layer simple closure technique without urinary diversion. An 80 percent success rate was achieved following the initial closure. A second simple closure of those which failed also succeeded in 80 percent of the cases. PMID- 8470328 TI - Vesicoureteral reflux in infants under one year old. Follow-up study and consideration on development of renal scarring. AB - In an attempt to clarify reflux nephropathy (RN), 67 infants aged under one year with vesicoureteral reflux (VUR) were retrospectively classified into two groups, non-surgical and surgical. They were evaluated on VUR grading, VUR spontaneous cessation rate, and incidence of scarring. As a whole, spontaneous cessation rate was 61 percent. The cessation rate was higher for infants with lower VUR grading. The average age at cessation was 2.5 years. Some patients showed no scarring at presentation despite severe VUR. However, most cases of renal scarrings at the time of presentation belonged to grade IV or V. Scarring advanced in 3 kidneys of the non-surgical group and in 13 kidneys of the surgical group. Of these 16 kidneys, 7 were rated as grade IV and 9 as grade V. An association between development of scarring and recurrent urinary tract infections was suggested. PMID- 8470329 TI - Recurrent urinary tract infections and intermittent left flank pain in young woman. PMID- 8470330 TI - Ureteral fibroepithelial polyp with positive urinary cytology. AB - We report on a patient with two fibroepithelial polyps of the upper ureter in whom the correct diagnosis was confused by finding voided urine as well as ureteral wash, and brush biopsy cytologies positive for malignancy. Fibroepithelial polyps and causes of falsely positive urinary cytology are reviewed. PMID- 8470331 TI - Canine bladder response to red and green light whole bladder photodynamic therapy. AB - A normal canine bladder model was used to compare the effects of red and green light whole bladder photodynamic therapy (PDT). Eighteen dogs were treated with Photofrin 1 mg/kg and whole bladder irradiation with red or green light at doses ranging from 20 to 60 J/cm2. Toxicity was assessed using cystometry, cystoscopy, and histopathology. Green light produced more significant vesical toxicity than red light, and this toxicity tended to vary with the light dose administered. Whole bladder PDT with green light at doses greater than 20 J/cm2 resulted in permanent reductions in bladder capacity. Conversely, a green light dose of 20 J/cm2 and red light doses ranging from 20 to 60 J/cm2 did not produce any significant permanent reductions in bladder capacity. Thus, while green light may be more toxic to the bladder than red light, there are distinct combinations of red or green light and Photofrin which can be used in the canine bladder to achieve mucosal degradation without causing permanent vesical dysfunction. PMID- 8470332 TI - Calcitonin gene-related peptide: possibly neurotransmitter contributes to penile erection in monkeys. AB - The distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the cavernous tissue and the erectile response to intracavernous injection of CGRP was investigated in 7 monkeys. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Intracavernous injection of CGRP antibody did not significantly change the erectile response to cavernous nerve stimulation. Histologic staining for CGRP immunoreactivity showed nerve fiber-like staining within the cavernous arterial wall and the cavernous smooth muscles. These data suggest that CGRP may contribute to penile erection in monkeys. PMID- 8470333 TI - Involvement of CD8+ T cells in delayed-type hypersensitivity responses against bovine leukemia virus (BLV) induced in sheep vaccinated with recombinant vaccinia virus expressing BLV envelope glycoprotein. AB - Delayed-type hypersensitivity responses against bovine leukemia virus (BLV) envelope glycoprotein (gp60) were induced in the skin of sheep vaccinated with recombinant vaccinia virus (RVV) expressing BLV glycoprotein. The lesions were characterized by marked infiltration of lymphocytes, slight migration of neutrophils, eosinophils, and macrophages in the dermis to hypodermis, and partial intercellular edema in the reticular layer. Immunohistochemical analysis with monoclonal antibodies demonstrated that the lymphocytic infiltrates consisted mainly of CD8+ T cells (53.7-55.8% at 48 hours post-challenge of BLV), CD4+ T cells (24.7-26.7%), and B cells (11.5-16.9%). The role of CD4+ and CD8+ T cells in suppressing BLV growth in RVV-vaccinated animals is discussed. PMID- 8470334 TI - Placental pathology of the pregnant mouse inoculated with Brucella abortus strain 2308. AB - Fifty-five pregnant BALB/c mice received various doses of Brucella abortus virulent strain 2308 intraperitoneally on day 9 of gestation, and uteri and spleens were examined at 3, 5, 7, and 9 days post-inoculation to study the pathogenesis of infection. A dose of 10(5.7) B. abortus organisms produced a severe, necrosuppurative placentitis. Bacteria multiplied preferentially within the placenta and were identified within the rough endoplasmic reticulum of trophoblast giant cells and within the visceral yolk sac endoderm. Abortions did not occur, but infarction of the labyrinth region of severely affected placentas occasionally resulted in fetal death. The severity of infection in the spleens of nonpregnant mice receiving the same challenge dose was not significantly different from that in the spleens of challenged pregnant mice. These results suggest that the sensitivity of the pregnant mouse to placental brucellosis is not due to a generalized immunosuppression but rather may involve a combination of local suppression of the immune response and a susceptible cell population suitable for Brucella colonization and replication. Experimental murine brucellosis resembles ruminant brucellosis and provides a model to study the intracellular replication of B. abortus in trophoblasts. PMID- 8470336 TI - Immunohistochemical evaluation of canine carcinomas with monoclonal antibody B72.3. AB - Monoclonal antibody (MAb) B72.3 reacts with a tumor-associated glycoprotein, designated TAG-72. TAG-72 has been identified in many human carcinomas but generally is not found in normal human tissues. Because of its proven utility in the diagnosis of human carcinomas, MAb B72.3 was applied to several different types of canine carcinomas. Five types of formalin-fixed, paraffin-embedded canine carcinomas were evaluated for immunoreactivity with MAb B72.3 by use of an avidin biotin immunoperoxidase complex method. Samples were considered positive when > or = 5% of all malignant cells contained a distinct intracellular stain. Immunoreactivity for MAb B72.3 was observed in 6/9 (67%) pulmonary adenocarcinomas, 7/13 (54%) transitional cell carcinomas, 7/11 (64%) mammary adenocarcinomas, 7/11 (64%) nasal adenocarcinomas, and 1/2 (50%) prostatic adenocarcinomas. The average cellular staining for positive carcinomas was 25%. Normal canine tissues from similar anatomic sites had little or no individual cell immunoreactivity. These preliminary results indicate that some canine carcinomas may express a tumor-associated antigen that is similar to TAG-72 and that MAb B72.3 immunoreactivity may be of diagnostic significance in classifying animal tumors. PMID- 8470335 TI - Bovine beta-mannosidosis: pathologic and genetic findings in Salers calves. AB - beta-mannosidosis is a recently recognized lysosomal storage disease in newborn Salers calves. Fourteen calves with beta-mannosidase deficiency were examined. Twelve calves were from routine laboratory submissions, and two calves were the result of a breeding trial. Salers calves with beta-mannosidase deficiency were of normal gestational weight, 36 +/- 6 kg, but were affected at birth. The head was moderately domed, and there was mild superior brachygnathism. The calves were recumbent and had a head tremor. There was bilateral renal enlargement, severe hypomyelination in the brain and variable thyroid gland enlargement. Severe cytoplasmic vacuolation was present within neurons, tubule epithelial cells, follicular cells and macrophages of the nervous, renal, thyroid and lymphoid tissues, respectively. Pedigree analysis and breeding trial results were consistent with an autosomal recessive disease. An initial biochemical survey of 1,494 Salers cattle indicated a carrier frequency of 23%. PMID- 8470337 TI - Adenomatous hyperplasia of equine allantoic epithelium. AB - Adenomatous hyperplasia with or without cystic formation of allantoic epithelium was observed in 63/954 equine placentas examined from 1 February 1988 to 31 January 1990. In 61/63 placentas, the adenomatous hyperplasia was associated with other placental lesions: 49 with chronic or chronic-active placentitis, six with placental edema, three with fetal diarrhea, one with placentitis and fetal diarrhea, one with fetal diarrhea and placental edema, and one with hyperplasia of chorionic epithelium. When lesions were less severe, the hyperplastic lesions were not grossly visible, but when lesions were severe, nodular, tumorous, cystic masses were observed at or near the insertion site of umbilical blood vessels. Histologically, lesions classified as stage 1 were characterized by hypertrophy and hyperplasia of epithelial cells and formation of intraepithelial glands (lumina). Lesions classified as stage 2 were characterized by the presence of fibro-adenomatous changes in the allantoic stroma. Lesions classified as stage 3 were characterized by the formation of the nodular masses, which were composed of glandular or cystic structures of various sizes lined by cuboidal or low to medium columnar epithelium. These glands or cysts were empty or contained amphophilic secretion, a mixture of neutrophils and secretion material, or neutrophils. The cause of adenomatous hyperplasia of the equine allantois is not certain; however, there is a close connection between chronic placental disorders and this hyperplastic lesion. PMID- 8470338 TI - Histologic and immunohistochemical studies of granular cell tumors in seven dogs, three cats, one horse, and one bird. AB - In a retrospective study, granular cell tumors in six dogs (Nos. 1-6), three cats (Nos. 1-3), one horse (No. 1), and one cockatiel (Nymphicus hollandicus) (No. 1) and a meningioma with a granular cell component in one dog (No. 7) were examined histologically and immunohistochemically. These tumors were identified by histologic examination of surgical biopsy specimens, except in the horse, in which the tumor was an incidental finding at necropsy. These diagnoses were initially made by more than one pathologist. Five of the six granular cell tumors in the dogs were in the oral cavity; one of these was in the maxillary gingiva of a 6-month-old puppy. The tumors in the cats were located in the tongue, vulva, and digit. The tumor in the horse was in the lung, and the tumor in the cockatiel was in the periocular tissue. Histologically, all granular cell tumors were characterized by oval to polygonal cells of various sizes. The cells had abundant, pale, eosinophilic cytoplasm with distinct intracytoplasmic granules, distinct cell margins, and mostly central nuclei. In the dogs, the gingival tumor had a large amount of collagen tissue, the tumor in the tongue had dilated blood vessels, and the maxillary tumor in the puppy was more cellular than the other tumors. The tumors in the cats were more anaplastic than the other tumors; one, located in the digit, was considered malignant. The granules in all of the tumors stained with periodic acid-Schiff and were diastase resistant. On staining with Luxol fast blue, the granules of all tumors stained different shades of pink, with the exception of the tumor in the tongue of a cat, which stained bluish green. Immunocytochemically, all tumors except the tumor in the cockatiel reacted against antibodies to vimentin. The granular cell tumor in the lung of the horse and the intracranial meningioma in a dog reacted to the antibody S-100 protein; the tumor in the horse reacted to neuron-specific enolase; tumors in two dogs (gingiva and skin) reacted to L-antitrypsin, and the maxillary tumor also reacted to lysozyme; the malignant tumor in the digit of a cat and the periocular tumor in the cockatiel reacted to muscle common actin and actin; the tumor in the cockatiel also reacted to desmin. Results of these immunocytochemical studies suggest that granular cell tumors, like tumors composed of rhabdoid cells, clear cells, and oncocytes, can have similar morphologic features but be of different cellular origins. PMID- 8470339 TI - Acute megakaryoblastic leukemia in one cat and two dogs. AB - The clinical, hematologic, and histologic features of acute megakaryoblastic leukemia are described for an 8-year-old female Domestic Shorthair cat, a 3-year old female mixed-breed dog, and a 3-year-old male German Shepherd Dog. The neoplastic cells were characterized as belonging to the megakaryocytic lineage. The following techniques were used: electron microscopy; detection of antibodies against human von Willebrand factor (vWF) and human platelet glycoprotein GP IIIa using a modified avidin biotin peroxidase complex technique on formalin-fixed paraffin sections; and enzyme histochemical methods on plastic sections for alkaline phosphatase, acid phosphatase, myeloperoxidase, alpha-naphthyl acetate esterase, alpha-naphthyl butyrate esterase, naphthol AS acetate esterase, and naphthol AS-D chloroacetate esterase. In addition, benign megakaryocytic cells, platelets, and neoplastic cells were labeled with lectins that have partially been shown to bind to platelet glycoproteins of other species. In healthy cats and dogs, the megakaryocytes and platelets reacted with lectins PSA, LCA, PHA-L, and WGA. Megakaryocytes and platelets from healthy cats were also labeled by lectin PNA. The lectins PHA-L and WGA reacted with neoplastic cells from the cat and both dogs. Lectin PNA bound to neoplastic cells from the cat, and lectins PSA, LCA, and SBA bound to neoplastic cells from both dogs. For the retrospective examination of paraffin-embedded material, the detection of vWF and GP IIIa appears to be the most reliable method for the identification of megakaryocytic cells. PMID- 8470340 TI - Granulated round cell tumor of cats. AB - Morphologic and biologic features of five feline granulated round cell tumours were compared with those previously reported to be of globule leukocyte and large granular lymphocyte origin. The five cats ranged from 6 to 9 years of age and presented with nonspecific gastrointestinal signs. Four of the five cats were tested for feline leukemia virus and were negative by enzyme-linked immunosorbent assay. The neoplastic process involved the abdominal cavity in all cases, with a predilection for the distal small intestine and mesentery. The liver and peripheral and thoracic lymphoid tissues were also sporadically affected. Neoplastic round cells contained 0.5-1.5-microns eosinophilic cytoplasmic granules that were difficult to discern on causal observation with hematoxylin and eosin stain but were deep blue and easily visualized when stained with phosphotungstic acid-hematoxylin. In two cases, epithelium in the affected ileum and liver contained unusually large numbers of apparently normal globule leukocytes. Ultrastructurally, the tumor granules tended to cluster at one nuclear pole and were spindle to round in shape with variably dense contents. Some granules contained a dense "cap" at one end or internal crystalloid bars that distorted the granule membrane. The tumors reported herein are similar to all three of the previously reported feline granulated round cell tumors and probably have a common cellular origin. PMID- 8470341 TI - Nodular granulomatous posthitis caused by Halicephalobus (syn. Micronema) sp. in a horse. PMID- 8470342 TI - A pseudolipoma on the diaphragmatic surface of the liver in a female B6C3F1 mouse. PMID- 8470343 TI - Bronchoalveolar eosinophilic cells in a canine model of asthma: two distinctive populations. AB - In a canine model of asthma, the identity and relationships of two types of cells with eosinophilic granules found in bronchoalveolar lavage (BAL) were investigated. Five female and three male newborn mongrel dogs were sensitized by intraperitoneal injection of 500 micrograms ragweed in 30 mg aluminum hydroxide repeated weekly for 8 weeks and then biweekly until 16 weeks of age. Three female and two male littermate controls received 30 mg aluminum hydroxide. From 4 months of age, dogs received six breaths of wet-nebulized ragweed solution through an endotracheal tube bimonthly. Bronchoalveolar lavage was performed 2 months or more after the last exposure to ragweed and was repeated 5 hours after ragweed inhalation. Dogs studied were 15 to 38 months of age. Eosinophilic cell populations were determined in BAL and peripheral blood; cells were examined by light and electron microscopy. Two eosinophilic cell types were in BAL: an eosinophil and an atypical cell with globule leukocyte characteristics. Specific microgranules, a constant feature of eosinophils, were prominent in the atypical cell and suggest a relationship to the eosinophil granulocyte series for the atypical cell and cells identified by others as globule leukocytes. In ragweed sensitized animals, there were more eosinophilic cells in BAL fluid and more eosinophils in peripheral blood. There was a proportional increase in BAL eosinophils 5 hours after ragweed inhalation and a corresponding decline in peripheral blood eosinophils. There was no increase in numbers of eosinophils in the sensitized animals; eosinophil and atypical cell numbers in littermate controls were unchanged. PMID- 8470344 TI - Efficacy of an Australian Babesia bovis vaccine strain in Malawi. AB - Three calves vaccinated with the Australian Ka strain of Babesia bovis were fully protected against experimental infection with an isolate from a farm on which four of 210 vaccinated cattle had died from B bovis infection. A degree of cross protection against the isolate was demonstrated in one calf which had been infected previously with Babesia bigemina. PMID- 8470345 TI - Duodenal perforations and gastric ulcers in foals. AB - The history, clinical signs, post mortem and histopathological findings from two foals with perforating gastroduodenal ulcers and one foal with a non-perforating gastric ulcer are compared with those of other species with similar lesions. Two of the foals had several erosions in the oesophageal mucosa and the condition had been associated with strictures in the duodenum. The cause of the disease remains obscure but a possible connection with stress has been suggested. PMID- 8470346 TI - Bovine spongiform encephalopathy: observations on the incidence during 1992. PMID- 8470347 TI - Improved detection of the beta-agonist clenbuterol by analysis of retina extracts. PMID- 8470348 TI - Nocardia asteroides mastitis in a small Argentinian herd. PMID- 8470349 TI - Absence of circulating TNF alpha in experimental bovine pneumonic pasteurellosis. PMID- 8470350 TI - The natural occurrence of aflatoxin B1 in Moroccan poultry feeds. AB - The occurrence of AFB1 in Moroccan poultry feeds and their ingredients was evaluated. Thirty poultry farms and 4 feedmills were surveyed from September 1989 to June 1991, and 300-500 g each of feeds (corn, sorghum, wheat bran, soybean meal, cottonseed meal, sunflower meal, finished feeds) were sampled. Additionally, on farms with suspected mycotoxin problems, necropsies of affected chickens were performed for gross and microscopic examinations. A total of 315 samples were analysed for AFB1 using a semi-quantitative enzyme linked immuno sorbent assay (ELISA kits) and thin-layer chromatography. In feedmills, 4% of samples contained AFB1; 17% among sunflower meal samples (20-80 ppb) and 4% among corn (110 ppb) and mixed feed samples (20-110 ppb). On poultry farms, 17% of samples were found contaminated with AFB1; 20% were positive among pellets and 16% among crumbles and 15% mash feeds. The level of contamination ranged from 20 ppb to 200 ppb, except for 4 samples that contained high levels of AFB1 (2000 5625 ppb). These highly-contaminated samples were associated with clinical aflatoxicosis in broiler chickens. The most frequent incidence of AFB1 contamination and the highest AFB1 contamination occurred in feeding troughs (23%). Aflatoxins should be considered potential contaminants of poultry feeds under Moroccan conditions. PMID- 8470351 TI - Effects of vitamin E on cadmium-induced locomotor dysfunctions in rats. AB - The effect of co-administration of vitamin E (VE) on cadmium (Cd)-induced locomotor deficits in growing rats was investigated. Intraperitoneal administration of 0.4 mg Cd/kg/d for 4 w resulted in significant decreases in time of ambulation and stereotype and numbers of stereotypic and vertical movements, but the resting time was enhanced. Administration of VE (5 mg alpha - tocopherol acetate/kg im on alternate days) to these rats effectively antagonised these locomotor deficits. The data support the hypothesis that Cd may induce oxidative stress in the CNS and that treatment with an antioxidant may be beneficial against such damage. PMID- 8470352 TI - Effects of hepatic P-450 enzyme inhibitors and inducers on the duration of xylazine + ketamine anesthesia in broiler chickens and mice. AB - We previously showed that pretreatment with inhibitors of hepatic P-450 microsomal enzymes prolonged xylazine-ketamine anesthesia, which sometimes led to mortality in rats. In this study we determined if similar effects were produced in broiler chickens and mice. A combination of 5 mg xylazine/kg and 15 mg ketamine/kg im was given to broiler chickens 5-6 w of age, and a combination of 10 mg xylazine/kg and 200 mg ketamine/kg ip was given to mice. The loss of righting reflex was used to measure duration of anesthesia. Pretreatment with 100 mg chloramphenicol/kg im, 150 mg cimetidine/kg im, 25 mg SKF-525A/kg im or 40 mg ketoconazole/kg po significantly increased the duration of xylazine + ketamine anesthesia in the chickens. Pretreatment with 40 mg phenobarbital/kg im bid for 3 d, 25 mg 3-methylcholanthrene/kg im sid for 3 d, or 50 mg rifampin/kg im bid for 2 d failed to alter the duration of xylazine + ketamine anesthesia in the broilers. None of the inhibitors tested altered the duration of anesthesia in mice. Some chickens pretreated with inhibitors (cimetidine, ketoconazole, SKF 525A) or inducers (phenobarbital, 3-MC, rifampin) died. This study suggests that hepatic metabolism of xylazine may be similar in the rat and broiler chicken and that the pulmonary metabolism of xylazine and ketamine may be different in chickens and rats. PMID- 8470353 TI - Flatpea intoxication in sheep and indications of ruminal adaptation. AB - This paper describes the signs of toxicity when seed-bearing flatpea (Lathyrus sylvestris L) hay is fed to sheep. Signs of intoxication (including seizure, muscular trembling and spasmotic torticollis) are similar to those observed for ammonia toxicity in ruminants. Accumulation of ammonia may be a direct consequence of flatpea ingestion, given that 2,4-diaminobutyric acid (DABA, a toxic constituent of flatpea) is known to inhibit hepatic urea synthesis. However, other modes of toxicity for DABA as well as other flatpea toxins may also contribute to this process of intoxication. Our evidence suggests that ruminal microbes are responsible for flatpea detoxification and host animal protection. The adaptation of sheep to flatpea may be a consequence of enhanced ruminal detoxification activity. Ruminal protective functions can be disrupted, however, through abrupt monensin feeding or the replacement of nonadapted for adapted rumen contents. This disruption temporarily suppresses mechanisms of ruminal detoxification. As a consequence sheep can again be made vulnerable to flatpea intoxication. PMID- 8470355 TI - Red cell and plasma concentrations of fluoxetine and norfluoxetine. AB - To study the distribution of fluoxetine and norfluoxetine in blood compartments we determined their concentrations in red cells and plasma after the addition of 500 ng/ml of each compound to human blood in vitro. Red cell and plasma fluoxetine concentrations were 493 +/- 79 ng/ml and 454 +/- 53 ng/ml, respectively (P > 0.1). To assess the potential implications of this distribution on routine monitoring of these compounds in plasma, we determined fluoxetine and norfluoxetine concentrations in red cells and plasma in 6 patients receiving various doses of fluoxetine. While in 4 patients the concentrations of fluoxetine and norfluoxetine in red cells and plasma were comparable, 2 patients had higher concentrations of both compounds in red cells. Variations in the distribution of fluoxetine and norfluoxetine in blood compartments are relatively small. Plasma levels may reflect the drug concentration in whole blood more reliably for fluoxetine and norfluoxetine than for tricyclic antidepressants. PMID- 8470354 TI - The toxic effects of mature flatpea (Lathyrus sylvestris L cv Lathco) on sheep. AB - The toxic effects of mature, seed-bearing flatpea (Lathyrus sylvestris L cv Lathco) hay on sheep was studied in a feeding trial with 25 adult ewes. Five ewes were barren; 20 were in the last 10 w of pregnancy. The ewes were blocked by weight and reproductive status for assignment to treatment groups. Four groups of 5 ewes each were allotted to 1 of the following diets: 0% (controls), 35.0%, 52.5% or 70.0% flatpea (FP); and 1 group of 5 ewes was allotted to a diet of increasing levels of 17.5, 35.0, 52.5 and 70.0% FP. Flatpea hay was harvested in the mature, seed-bearing stage, pelleted, reground and incorporated into a basal (control) diet of 30% corn + 70% alfalfa by substitution of an appropriate amount of FP for alfalfa. The resulting diets were fed for up to 42 days. The toxic nature of FP was expressed by the following dose-related responses: Fluctuating reductions in feed intake upon initiation of diets containing 35% FP and above; occurrence of a potentially fatal, acute central nervous system syndrome at FP levels as low as 35%; and reduced weight gain at FP levels of 52.5% and above. A wasting condition was observed in 1 ewe fed 52.5% FP. Four of 5 ewes and 1 lamb fed increasing levels of FP developed acute poisoning. One of these ewes developed acute neurotoxicosis when consuming 52.5% FP; 3 other ewes and 1 40-d old orphaned lamb developed neurotoxicosis upon raising the FP level to 70.0%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470356 TI - Experimental citrinin nephrotoxicosis in dogs: renal function evaluation. AB - To assess renal function changes in acute nephrotoxicosis in dogs, the development and evolution of renal damage during induced citrinin intoxication were studied. Six dogs (experimental group) were given 10 mg citrinin/kg/BW every 24 h during 2 d, and 5 dogs (control group) received exclusively the diluent (1 ml 1% sodium carbonate/kg/BW/d for 2 d). The dogs were daily submitted to physical examination, urinalysis and blood biochemistry analyses (blood urea, serum creatinine, potassium, sodium and glucose) during 2 w. The citrinin-induced renal lesions were mainly in the proximal convoluted tubule and characterized by proteinuria, glucosuria and the presence of numerous granular casts in the urine sediment; these could be detected before elevations in blood urea and creatinine. Glucosuria was the earliest abnormality found and lasted 5 d, while proteinuria and cylindruria were observed from days 1 to 5 and from days 1 to 15, respectively. The glomerular filtration rate was slightly affected as observed by blood urea and creatinine elevations from days 2 to 5. Urine analysis is a useful tool for the evaluation of nephrotoxicity since most nephrotoxins act primarily on the proximal convoluted tubule. PMID- 8470357 TI - Sump additives as a source of bioaerosols in a school building. AB - An investigation was launched following complaints of poor air quality and building-related illness in a public elementary school. Occlusion of air intakes put the building under negative pressure and caused vents from a below-ground sump to become air intakes. Outside air drawn through the sump pit traveled into the adjacent main air handling unit and was disseminated throughout the building. Sump additives introduced in an attempt to counteract foul odors contained spores of Bacillus species, which appeared as bioaerosols throughout the school. Viable microbial sampling identified B subtilis, B cereus, and B licheniformis in the sump room and classrooms at levels as high as 760 colony forming units/m3 (CFU/m3). Concentrations of CO2 in classrooms were 1250 ppm, indicating inadequate makeup air. Remediation was accomplished by opening the air intakes, isolating the sump room from the air handling system, venting the sump to the outside, and flushing the sump with fresh water on a regular basis. PMID- 8470358 TI - Ryegrass staggers in heifers: a new mycotoxicosis in Argentina. AB - Aberdeen Angus (AA) and crossbred AA x Hereford 8-9 mo old heifers (560 animals) showed a typical perennial ryegrass (PRG) staggers syndrome after grazing 26 d in a 25-hectare paddock of pure Lolium perenne. Effects were observed in about 50% of the herd. When forced to move, the animals showed incoordination, weakening of the forelimbs, falling on the chest and neck, and moving in this position during the first steps before recovering a normal gait. In severely affected animals all of the 4 limbs had extreme rigidity. All the affected animals had generalized tremors. Twelve days after removal from this pasture the animals had no symptoms. The symptoms described, the pasture conditions (mostly PRG stubble and short PRG green plants in slow growth), a positive mouse bioassay of extracts obtained from the basal part of the PRG plants, and the microscopic finding of Acremonium lolii hyphae in the leaf sheaths of the same plant material produced diagnostic evidence to confirm this as a PRG staggers case, the first reported in Argentina. PMID- 8470359 TI - Acute overdosage with thioridazine: a review of the available clinical exposure. AB - Two hundred and twenty-three cases of acute overdosage associated with thioridazine were reviewed. The most frequent feature was impairment of consciousness which was linearly dose-related and occasionally resulted in life threatening complications. Arrhythmia was the most frequently reported serious toxic effect. Patients presenting with anoxia were at risk for arrhythmia, as were patients ingesting a high dose. Arrhythmia may, by decreasing cardiac output, predispose to the occurrence of all other observed complications (ie, pulmonary edema, severe hypotension and renal failure). Therefore, treatment of arrhythmias should be the keystone of management of thioridazine overdosage. Torsade de pointes was reported only once with overdosage. Isolated ventricular arrhythmias (VA) occurred at high doses (median 12 g). At lower doses (median 5 g), VA were frequently associated with conduction disturbances, which were not, as such, statistically predictive of arrhythmias. Since thioridazine in high doses exhibits a beta-adrenoceptor and a verapamil-like calcium channel blocking effect, drugs with these types of properties are contraindicated. VA may be refractory to lidocaine or recur after such therapy. Transient cardiac pacing appears to be the most appropriate management of VA. Although its efficacy is established for the treatment of phenothiazine-induced arrhythmias, its use remains rare (only 3/50 cases). PMID- 8470361 TI - A review of Heinz-body anemia in the dog induced by toxins. AB - Heinz-body anemia is uncommon in the dog. We review the available literature and discuss onions, methylene blue, acetaminophen, zinc, benzocaine, vitamin K and phenylhydrazine as toxic materials capable of inducing Heinz-body formation in the dog. PMID- 8470360 TI - A review of the toxicology of the antibiotic MICOTIL 300. AB - MICOTIL 300 is a new macrolide antibiotic for the treatment of Bovine Respiratory Disease complex. As with other macrolides used in human and veterinary medicine, overdoses of MICOTIL do not produce pathognomonic lesions. The toxicity dose response varies among laboratory animal and domestic livestock species. However, clinical evidence of MICOTIL toxicity due to large doses is generally a manifestation of the positive chronotropic and negative inotropic cardiovascular effects. No adverse environmental effects are expected from the use of MICOTIL in cattle. PMID- 8470362 TI - The effectiveness of a remote access hotline service for the handling of night shift calls. AB - In order to justify dedicated staff for night calls, improve the quality of our handling of these calls, and qualify for certification by the AAPCC, we sought an alternative to hiring dedicated night staff. We offered our certified staff members the opportunity to fulfill part of their regular duties answering night calls from home. We set them up with a computer system, dedicated telephone line, texts and consultant information. They were able to access the Poison Center hotline computer via a remote access program. A significant increase took place in the number of documented calls to the Poison Center during the midnight to 8:00 am shift. Quality of documentation also improved significantly and level of service has been complemented by callers. The remote access method is a viable way for a small Poison Center to cover the night shift with certified, reliable, capable staff. This method of call answering has solved our major problem of hiring night staff who would satisfy requirements and provide excellent service. PMID- 8470363 TI - Washington's ER physicians' perceptions of poison centers. PMID- 8470364 TI - Ineffectiveness of a mass mailing campaign to improve poison center awareness in a rural population. AB - The distribution of poison prevention and education literature represents a significant part of poison center outreach programs. Yet the effectiveness, in terms of cost and impact, of mailing this material in an unsolicited fashion has not been investigated. We questioned the effectiveness of poison education literature through mass mailing to increase poison center awareness and improve one's ability to comprehend and retain appropriate first aid response in the event of a poisoning emergency. Two poison education brochures, in English and Spanish translation, and 2 telephone stickers were mailed third class to all 8,948 households in 1 rural county at a total cost of $3,420. A total of 397 (4.4%) households were randomly selected and successfully completed a 23-question telephone survey 6 mo after the mailing. The primary language spoken by the respondents were English, 311 (78%) and Spanish, 86 (22%). Children under the age of 6 y were present in 101 (25%) households. Only 50 (13%) respondents remembered having received any poison education brochures. Although 147 (37%) responded that they had heard of the regional poison center, only 63 (16%) said they would call the poison center first in the event of a poisoning. Forty-four percent indicated they would call 911 first. Only a small increase in penetrance rate was found when comparing 6 mo periods before and after the mailing. We conclude that mass mailing of poison education brochures made little impact in improving poison center awareness and first aid response and was not a cost effective method of poison education. PMID- 8470365 TI - Content audit of POISINDEX. PMID- 8470366 TI - William the Conqueror and the murder of Conan II. PMID- 8470367 TI - The neurotoxin-like sequence of human immunodeficiency virus gp120: a comparison of sequence data from patients with and without neurological symptoms. AB - A region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp 120 has been claimed previously to be homologous to parts of snake venom neurotoxins and rabies virus glycoprotein ("the neurotoxic loop"). We have determined DNA sequences directly from a polymerase chain reaction amplified fragment corresponding to this region of HIV-1 gp 120 and have translated these to protein sequences. This was performed with the prototype HIVSF2 isolate and several Swedish HIV-1 strains, which were precultivated from blood cells or cerebrospinal fluid (CSF) or were directly obtained from CSF cells of patients with and without neurological symptoms. The results show that there are sequence similarities between a short segment of gp120 of clinical HIV-1 strains and the neurotoxic loop. The strains of patients with neurological symptoms did not, however, show a genetic shift of their sequences towards a greater similarity to the sequences of snake venom neurotoxins and rabies virus glycoprotein as compared to the strains of asymptomatic individuals. PMID- 8470368 TI - Molecular cloning and complete nucleotide sequence of genomic RNA of the AIK-C strain of attenuated measles virus. AB - Twelve cDNA clones covering the entire genome of the AIK-C strain of a seed for live measles vaccine were obtained, and the nucleotide sequences were determined. The full viral genomic RNA consists of 15,894 nucleotides. Comparisons of the nucleotide sequence and the deduced amino acid sequence between the AIK-C and other Edmonston strains revealed the following changes: 56 nucleotide differences and one C residue insertion, 31 amino acid changes, and 19 silent mutations. PMID- 8470369 TI - Comparative sequence analysis of the M gene among rabies virus strains and its expression by recombinant vaccinia virus. AB - Nucleotide sequences and the deduced amino acid sequences of the gene encoding the matrix (M) protein of the Nishigahara and the CVS strains of rabies virus have been determined. The M gene is 609 nucleotides long and is capable of coding for a peptide composed of 202 amino acids. Sequence comparison of these M genes with those of other stains [Pasteur (PV), ERA, Avol] revealed that there is 89.7 91.5% homology at the nucleotide level, and 90.1-92.1% homology at amino acid level, between almost all combinations of these strains. However, in the combinations of the PV and ERA strains, and the virulent CVS and the avirulent CVS-derived Avol strains, much higher homology was observed both at the nucleotide and amino acid levels. The predicted secondary structure and hydropathy profiles also exhibited similar features. Recombinant vaccinia virus containing the M gene was constructed. Sodium dodecyl sulfate (NaDodSO4) polyacrylamide gel electrophoresis of the precipitates obtained by immune reaction of the recombinant virus-infected cell lysate with a monoclonal antibody against the M protein revealed that electrophoretic mobility of the expressed protein is indistinguishable from that of the authentic M protein from rabies virions. PMID- 8470370 TI - Gene A32 product of vaccinia virus may be an ATPase involved in viral DNA packaging as indicated by sequence comparisons with other putative viral ATPases. AB - Statistically significant sequence similarity was revealed between the gene A32 product of vaccinia virus (VV), gene I products (gpI) of filamentous single stranded DNA bacteriophages, and IVa2 gene products of adenoviruses. Four conserved sequence motifs were delineated, the two N-proximal of which correspond to the A and B motifs of the purine NTP-binding pattern. Based on the role of gpI and IVa2 proteins in virion morphogenesis, and on the conservation of the NTP binding pattern in these proteins, we hypothesize that the A32 gene product might be involved in an ATP-consuming function in VV virion formation, e.g., packaging of the DNA in the virus particle. PMID- 8470371 TI - Sequence and gene structure of the hepatitis E virus isolated from Myanmar. AB - Hepatitis E virus (HEV) is a causative agent of enterically transmitted non-A, non-B hepatitis. Hepatitis E occurs not only in sporadic forms but also in epidemic outbreaks in the developing world. We have revealed the nucleotide and predicted amino acid sequences of full cDNA of HEV isolated from sporadic hepatitis E of Myanmar. The genome is 7194 nucleotides long, followed by a poly(A) tail, and has three open reading frames. The nonstructural gene is located in the 5' terminus, while the structural gene is situated in the 3' terminus. Our HEV strain has 98.5% nucleic acid identity with the HEV strain cloned by workers at Genelabs Incorporated from Myanmar. The difference is point nucleotide substitutions. There is a high degree of nucleotide relatedness among HEVs isolated from the same geographical location. PMID- 8470372 TI - Nurses' perceptions about physical restraints. PMID- 8470373 TI - Psychiatric recidivism prediction factors. PMID- 8470374 TI - Predicting breast-feeding duration during the postpartum hospitalization. PMID- 8470375 TI - Development of the Prenatal Attachment Inventory. PMID- 8470376 TI - Circular victimization in the caregiving relationship. PMID- 8470377 TI - Israeli RNs' projected work plans. PMID- 8470378 TI - Establishing guidelines to determine whether a potential study is a quality assessment study or scientific research. PMID- 8470379 TI - Qualitative research: the evaluation of its credibility, fittingness, and auditability. AB - The three criteria of credibility, fittingness, and auditability have been focused on in the hope of facilitating the critique of qualitative research. Once criteria that are appropriate to qualitative methodologies are developed, the scientific merit of these research studies can truly be appreciated. If traditional scientific criteria relevant to quantitative studies are used to critique qualitative methods, the development and acceptance of this paradigm transcending research will be hindered. PMID- 8470380 TI - Botulinum toxin. From poison to medicine. AB - Although thousands of people in the world each year continue to be poisoned with botulinum toxin-food-borne, infantile, or wound botulism-the neurotoxin is now sufficiently understood to allow it to be used as a medicinal agent to paralyze specific muscles, giving temporary symptomatic relief from a variety of dystonic neurologic disorders. I review some of the epidemiologic, clinical, and pathophysiologic aspects of botulinum toxin and how the neurotoxin may act as a poison or a medicine. PMID- 8470381 TI - Homeless families and their children's health problems. A Utah urban experience. AB - Descriptive information was obtained about homeless families in the Intermountain West and their children's health care needs were defined to help professionals develop programs tailored to meet the unique needs of this population. We collected data during the well-child visits of 306 children in 161 families living at the Travelers Aid Society family shelter. The results reveal 2 types of homeless families, episodic and long term. Each requires different levels of assistance. This study's profile of mobile, predominantly white, 2-parent families with few children (mean of 1.2) differs considerably from that of studies conducted on the East and West coasts. The families' nomadic life-style (73.1% came from 32 states other than Utah) present important public health issues, especially because of the recent resurgence of tuberculosis and declining levels of childhood immunizations. The children's health problems were similar to those reported nationally: delayed immunizations, dental decay, anemia, and impaired vision. PMID- 8470382 TI - Controversies in measles immunization recommendations. AB - Controversy in medicine is inevitable, but it becomes problematic when the issue is a serious public health problem requiring a clear plan of action. In recent years measles has made a major resurgence in this country, with provisional figures showing 89 measles-related deaths in 1990. The Immunization Practices Advisory Committee of the US Public Health Service, the Committee on Infectious Diseases of the American Academy of Pediatrics, and the US Preventive Services Task Force have all issued recommendations for measles immunization. Most of these recommendations are in agreement, but they conflict on the age at which vaccination should be given and the number of doses. To assist physicians in disentangling this complex web, I review the history of measles immunization in the United States and give the rationale for particular positions wherein the groups disagree. I describe protocols for routine vaccinations, endemic areas, outbreak control, colleges and universities, and international travel. PMID- 8470383 TI - HIV-1 seroprevalence among women attending sexually transmitted disease clinics in California. California Family of Surveys and Sentinel Surveillance Consortia. AB - To evaluate the distribution of the human immunodeficiency virus type 1 (HIV-1) epidemic among California women, we analyzed HIV-1 seroprevalence and risk factors among women attending sexually transmitted disease (STD) clinics in 21 local health jurisdictions. Using standardized protocols developed by the Centers for Disease Control, we tested unlinked serum specimens from women attending participating STD clinics in 1989. We analyzed demographic characteristics, HIV risk exposure groups, and results of HIV-1 antibody testing on 17,210 specimens with an overall HIV-1 seroprevalence of 0.57%. Seroprevalence rates were highest for African-American women, women 25 to 29 years of age, injection drug users, and women attending STD clinics in San Francisco. After multiple logistic regression analysis, HIV-1 seropositivity remained highest for these four groups. The rate of HIV-1 infection among women attending STD clinics in California underscores the continued need to make HIV counseling and testing an integral component of routine services for women being evaluated for, or presenting with, sexually transmitted diseases. PMID- 8470384 TI - Does excluding patients without telephones affect the results of telephone reminder studies? AB - Studies of the effectiveness of telephone reminders to improve the rate of appointments kept have shown conflicting results. Few have accounted for patients without telephones. We conducted a controlled clinical trial to study the effect of excluding patients without telephones in a study of telephone reminders in an urban pediatric clinic. Telephone reminders were attempted the evening before scheduled visits for 238 subjects; 259 controls received no reminders. The overall rate of kept appointments was the same (54%) for both the intervention group and the control group. In neither group was there a substantial difference in the "show" rate between patients with and without telephones (intervention group 52% versus 57%, control group 55% versus 54%). In the intervention group, the show rate was higher for those with telephones who were contacted (66%) than for those who were not (37%) (P < .001). Telephone reminders did not improve the overall rate of kept appointments but appeared to result in a significant improvement in the show rate of those who could be reached. Excluding patients who could not be reached by telephone may affect the usefulness of previous studies. PMID- 8470385 TI - Prevention and treatment of foot problems in diabetes mellitus. A comprehensive program. AB - This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. PMID- 8470387 TI - Carotid endarterectomy. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in neurosurgery. Each item, in the judgement of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in neurosurgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Neurosurgery of the California Medical Association, and the summaries were prepared under its direction. PMID- 8470388 TI - The limits of treatment of malignant gliomas. PMID- 8470386 TI - Epidemiology of health and safety risks in agriculture and related industries. Practical applications for rural physicians. AB - Epidemiologic studies document that work in the agricultural sector is associated with many occupational health hazards. Exposure to organic dusts and airborne microorganisms and their toxins may lead to respiratory disorders. The burden of exposure-related chronic bronchitis, asthma, hypersensitivity pneumonitis, organic-dust toxic syndrome, and chronic airflow limitation can be diminished by appropriate preventive measures. The contribution of exposures to agricultural chemicals to cancers and neurodegenerative disorders is being investigated. Some studies document that farmers and those in related industries are at higher risk for the development of cancer of the stomach, soft tissue sarcoma, non-Hodgkin's lymphoma, and multiple myeloma. Chronic encephalopathy and Parkinson's and Alzheimer's diseases are being studied in relation to agricultural chemicals. The possible carcinogenicity and neurotoxicity of pesticides emphasize the need to promote the safe use of chemicals. Another area for health promotion programs is disabling injuries and traumatic deaths. Farm accidents are important because of their frequent occurrence among young people and disturbing fatality rates. Other health issues of concern in these industries include skin diseases, hearing loss, and stress. PMID- 8470389 TI - Indications and limitations of stereotactic radiosurgery. PMID- 8470390 TI - Corpus callosotomy for intractable epilepsy in children. PMID- 8470391 TI - Spinal cord injuries in children without radiographic abnormalities. PMID- 8470392 TI - Management of growth hormone-secreting pituitary adenomas--early diagnosis leads to successful treatment. PMID- 8470393 TI - Interventional neuroradiology--a new approach to difficult vascular lesions of the brain. PMID- 8470394 TI - Preventive aspects of helmet safety. PMID- 8470395 TI - Care of patients with aneurysms. PMID- 8470396 TI - Epilepsy surgery for hippocampal sclerosis. PMID- 8470397 TI - Metastatic spinal tumors. PMID- 8470398 TI - Pulmonary dirofilariasis in California. PMID- 8470399 TI - Sentinel surveillance and prevention of HIV in women. PMID- 8470400 TI - An optimistic message for foot problems in diabetes. PMID- 8470402 TI - Global health. PMID- 8470401 TI - The Los Angeles riots and the medical profession. PMID- 8470403 TI - Evaluation of recent changes in the financing of health services. Report of a WHO Study Group. PMID- 8470404 TI - [Typical errors in therapy of hypertension--an overview]. PMID- 8470405 TI - [Therapeutic drug monitoring in general practice--indications and interpretation]. PMID- 8470406 TI - [Rational diagnosis in kidney diseases]. PMID- 8470407 TI - [The phenomenon of persorption--history and facts]. PMID- 8470408 TI - [The importance of fasting and vegetarian diet in rheumatic diseases]. PMID- 8470409 TI - [Modern wound dressings. 2: Occlusive dressings]. PMID- 8470410 TI - [Diagnostic errors in cardiac arrhythmias]. PMID- 8470411 TI - [Diagnosis of cerebellopontile angle tumors--only a problem for specialists?]. PMID- 8470412 TI - [From general practice of an expert assessment service: the physician must monitor duration and dose of phototherapy]. PMID- 8470413 TI - [A case from general practice (7): A physician with heart symptoms]. PMID- 8470414 TI - [The diagnostic value of standard ECG methods, the cold-pressure test and Valsalva maneuver in idiopathic QT syndrome]. AB - The idiopathic Long QT Syndrome is an infrequently occurring disorder. Affected patients usually show ECG alterations and are prone to syncope and sudden arrhythmic cardiac death. Adequate therapy with beta-blocking drugs may significantly improve the prognosis of affected patients. The early and precise diagnosis of the disorder therefore has major prognostic impact. This paper reports the diagnostic significance of standard ECG, exercise stress testing, ambulatory ECG monitoring, cold pressor test and Valsalva maneuver in 14 patients with Long QT Syndrome. The results were compared with those obtained in 14 healthy age matched volunteers. QTc duration was significantly longer in patients with Long QT Syndrome during standard 12-lead ECG at rest (489 +/- 55 ms versus < vs. > 412 +/- 25 ms, p < 0.005), exercise stress test (490 +/- 39 ms vs. 409 +/- 18 ms, p < 0.001), cold pressor test (512 +/- 45 ms vs. 407 +/- 19 ms, p < 0.001), Valsalva maneuver (497 +/- 49 vs. 407 +/- 18 ms, p < 0.001), minimal heart rate during 24-h of ambulatory ECG monitoring (482 +/- 69 ms vs. 402 +/- 22 ms, p < 0.01) and maximal heart rate during Holter monitoring (460 +/- 47 ms vs. 411 +/- 27 ms, p < 0.005). Four of 14 patients with Long QT Syndrome had pathological findings during ambulatory ECG monitoring (two patients showed short episodes of asymptomatic torsade de pointes tachycardia, one patient had an intermittent SA-Block, and one patient showed T-wave alternans). All healthy volunteers had normal ambulatory ECG recordings (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470415 TI - [Comparison of the cardiodepressive effects of nifedipine, isradipine, nisoldipine and felodipine in patients with coronary heart disease]. AB - To compare the negative inotropic effects of the four dihydropyridine-calcium channel-blockers nifedipine (NIF), isradipine (ISR), nisoldipine (NIS) and felodipine (FEL) in man, the drugs were infused within 30 min intravenously in an equihypotensive dosage (NIF 2 mg, ISR 0.5 mg, NIS 0.5 mg, FEL 0.6 mg; 10 patients in each group) in patients with coronary heart disease. As a control, an additional 10 patients received isotonic saline solution following an identical protocol. The afterload reduction was submaximal (reduction of peripheral resistance: NIF -23 +/- 9%, ISR -24 +/- 10%, NIS -28 +/- 6%, FEL -27 +/- 6%; no significant difference for group comparison) with a similar kinetic and a steady state of the afterload reduction after one-half of the infusion period to achieve a comparable sympathetic reflex activation. Preload parameters (PAP, LVEDP) were unchanged in all groups. A reflex tachycardia occurred in all treatment groups after 15 min of drug infusion. Due to its negative chronotropic properties, the reflex tachycardia was significantly attenuated after isradipine as compared to the other drugs (heart-rate changes: NIF +13 +/- 7%, p < 0.01; ISR +4 +/- 7%, not significant; NIS +20 +/- 10%, p < 0.01; FEL +17 +/- 12%, p < 0.01). Because of the baroreflex and sympathetic reflex activation the left-ventricular dp/dtmax increased after isradipine (+14 +/- 10%, p < 0.01) and nisoldipine (+16 +/- 13%, p < 0.01). The lack of a significant dp/dtmax increase in spite of a comparable afterload reduction after felodipine (+5 +/- 8%, not significant) or nifedipine ( 3 +/- 6%, not significant) must be a consequence of the cardiodepressive properties of these drugs. Therefore, in an equihypotensive dosage, the strongest negative inotropic effects were observed after nifedipine, lesser effects after felodipine (p < 0.03), and the weakest cardiodepressive effects after isradipine (p < 0.01) and nisoldipine (p < 0.01). For clinical applications the lesser cardiodepressive properties of the new dihydropyridine-derivatives should be advantageous in patients with already reduced left-ventricular performance or for use in combination with other negative inotropic drugs, e.g., betablockers. PMID- 8470416 TI - [Does ST-elevation in stress ECG depend on the extent of collateral circulation?]. AB - As a possible cause of exercise-induced ST-elevation in patients without myocardial infarction, a poor or absent coronary circulation to the poststenotic coronary segment was postulated. To check this thesis, we examined 10 patients (pts.) with ST-elevation, respectively, ST-depression and comparable coronary status (coronary score 12 vs. 12; mean stenosis diameter 86 vs. 85%) and exercise parameters (work load 150 vs. 137.5 Watts; exercise duration 2.8 vs 3.5 min) with regard to their collateral circulation. In the group with ST-elevation there were nine pts. with severe proximal stenosis of the left anterior descending artery (LAD) and one pt. with a stenosis in the middle third of the right coronary artery. The 10 patients with ST-depression had a proximal stenosis in the LAD. The extent of the angiographically seen collaterals was equal in both groups. As a result, this study demonstrates that the size of the collateral circulation has no influence on the exercise-induced ST-elevation. The most plausible cause of exercise-induced ST-elevation is a functional decrease of the lumen of a severe stenosis. PMID- 8470417 TI - [Nitroglycerin in comparison with nifedipine in patients with hypertensive crisis]. AB - To determine whether nitroglycerin is just as effective as nifedipine in lowering the blood pressure in excessive hypertension and hypertensive crisis, two groups of 20 patients received in random sequence either 1.2 mg of nitroglycerin sublingually or a 10 mg nifedipine capsule, which was chewed and swallowed. The blood pressure fell after 5 min in the nitroglycerin group from 211/122 mm Hg to 171/95 mm Hg and after nifedipine from 210/118 to 185/102 mm Hg. The greater effect of nitroglycerin results from faster absorption through the oral mucosa than through the small intestinal mucosa where nifedipine is primarily absorbed. After 15 to 20 min a satisfactory reduction in blood pressure was reached in both groups: 157/91 and 158/92 mm Hg, respectively. After 30 min the heart rate in the nitroglycerin group had decreased from 83 to 80/min, but in the nifedipine group it had increased from 84 to 90/min. The reduction in blood pressure persisted up to 6 h. No significant difference in side-effects was determined. Since a hypertensive crisis is usually accompanied by left-ventricular failure, pulmonary edema or angina pectoris and infarction, and nitroglycerin has been definitively shown to positively influence these conditions, preference should be given to nitroglycerin in the treatment of hypertensive crisis. PMID- 8470419 TI - [Stable stimulation impedance of steroid electrodes in various impulse amplitudes: indications for low polarization of the electrode-myocardium interface]. AB - The reduction of electrode surface area leads to an increase of pacing impedance which may be caused either by higher tissue resistance or by greater polarization occurring at the electrode-myocardium interface. The impedance of steroid-eluting leads with both 8 mm2 surface area (CapSure 4003, Medtronic n = 12) and with 4 mm2 (030-368, Telectronics, n = 8) were compared to the impedance of a high polarizing Elgiloy lead (PE 60/4 DN, Biotronik; n = 7). All leads were connected to the same unipolar VVI pacemaker (Pasys 8329, Medtronic). Pacing impedance was measured at 0.8, 1.6, 2.5, 5.0, and 8.0 volts pulse amplitude and at 0.05, 0.25, 0.5, 1.0, 2.0 msec pulse duration. Impedance of the Elgiloy lead was constant at 0.05 and 0.25 msec, but increased at longer pulse durations for pulse amplitudes below 5.0 volts. Both steroid-eluting leads had constant impedance at each pulse duration. The impedance of the 4 mm2 lead was significantly higher than of the 8 mm2 lead. In contrast to the Elgiloy lead, impedance of the steroid-eluting leads is not influenced by pulse-dependent factors such as polarization, indicating that the higher impedance of the 4 mm2 steroid-eluting lead is caused by a higher tissue resistance and not by greater polarization. PMID- 8470418 TI - [Emergency management of type A aortic dissection in the acute rupture phase with pericardial tamponade]. AB - A case of successful operative repair of a previously unknown aortic dissection type A after intrapericardial rupture is presented. Under resuscitative measures an inferior pericardiotomy was done, followed by sternotomy to control bleeding under then stabilized circulation. Without detailed diagnostic evaluation, immediate operation with resection of the aneurysm and supracoronary prosthesis interposition was carried out. The diagnostic methods and problems, the differential diagnosis, and comparable cases from the literature are discussed. PMID- 8470420 TI - [8th report of structure and performance figures of heart catheterization laboratories in Germany. Results of a survey of the Commission for Clinical Cardiology of the German Society of Cardiovascular Research in 1991 with the cooperation of the German Society of Pediatric Cardiology]. PMID- 8470421 TI - [Long-term follow-up of patients with angina pectoris-like chest pain and normal coronary angiogram]. AB - To determine the long-term prognosis of patients (pts) with angina-like chest pain and normal coronary arteriograms, 178 pts (61 women, 117 men; mean age 48.1 years) were followed for an average of 9.8 years (5.5-13.1 years). Eight pts (4.5%) died during follow-up: One pt from acute myocardial infarction, one pt suddenly, one pt from chronic cor pulmonale and 5 pts from non-cardiac diseases. Chest pain remained constant in 137/170 surviving pts (80.6%), but disappeared in 33 pts (19.4%). Nine of the 178 pts (5.1%) developed manifest coronary artery disease (CAD): four of them (2.2%) acute myocardial infarctions including one death, after an average of 7.2 years; in five pts (2.8%) with continued chest pain a second coronary angiogram showed typical CAD. These pts with manifest CAD averaged 2.1 risk factors: six pts were smokers, two pts had elevated cholesterol levels (> 7.5 mmol/l), three pts had elevated triglyceride levels (> 2.4 mmol/l), two pts had a diabetes mellitus type IIa and six pts were hypertensives. Patients without manifestation of CAD averaged only 1.4 risk factors (p < 0.05). Our data show that pts with angina-like chest pain and normal coronary angiograms have an excellent long-term prognosis (only 0.51% of patients with new manifestations of CAD per year). However, angina-like chest pain can persist over many years. PMID- 8470422 TI - Indications for smallpox vaccination: policies still differ. AB - The need for vaccination of those handling vaccinia and other related orthopoxviruses is still uncertain, with UK and US authorities adopting different policies. The former revised an earlier decision and now no longer recommend vaccination; the latter confirmed earlier decisions to recommend vaccination. These policies are reviewed in the light of evidence on the safety and efficacy of smallpox vaccine. PMID- 8470423 TI - Immunogenicity of a recombinant DNA hepatitis B vaccine in renal transplant patients. AB - In renal transplant patients hepatitis B infection is associated with a higher morbidity and mortality. Therefore, we investigated the immunogenicity of an enhanced vaccination scheme with a recombinant DNA hepatitis B vaccine in renal allograft recipients. Injections of 40 micrograms were given at months 0, 1, 2 and 6. Conversion rate (anti-HBS antibody titre > 10 mIU ml-1) was only 36%. On the other hand, in patients vaccinated before transplantation, a booster injection of 40 micrograms was highly successful, resulting in a rise of antibody titre > 10 mIU ml-1 in 86%. In view of the poor vaccination results after transplantation, we strongly recommend hepatitis B vaccination prior to transplantation. PMID- 8470424 TI - Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule. AB - Inactivated subunit vaccines were prepared from high-growth reassortants derived from two separate egg isolates from a single clinical specimen of influenza A (H1N1) virus. One of these reassortants, NIB-14, was antigenically indistinguishable from isolates made in tissue culture, while the other, NIB-17, was antigenically different and typical of egg isolates. The viruses differed by three amino acid residues in the haemagglutinin (HA) molecule and the anti-HA serological response induced was studied in animal models and human volunteers. In the volunteer groups both vaccines induced very high levels of circulating haemagglutination inhibition antibodies but with different serological specificities. Both NIB-14 and NIB-17 vaccines induced high levels of cross reactive antibodies capable of reacting with both strains, but only NIB-14 vaccine induced significant levels of strain-specific antibodies capable of reacting exclusively with the homologous strain. Antisera containing only cross reactive antibodies proved as capable of virus neutralization as antisera containing high levels of strain-specific antibodies. We extended the argument that epidemic strains are antigenically more closely related to tissue culture isolates and established that viruses which differ by only single amino acids at critical points in the HA structure can induce a significantly different immune response when used as inactivated vaccines. PMID- 8470425 TI - Antibody levels determined by an appropriate technology (HI) in local cattle following anti-rinderpest campaign in Nigeria. AB - The levels of antibodies against rinderpest measured by the haemagglutination inhibition (HI) test were titrated in 640 randomly collected sera. Out of 640 samples, 586 (91%) exhibited high titres of > 4 while 54 (9%) had low titres of < or = 4. Of the 400 samples collected in Zaria, 354 (88.5%) had high titres while 46 (11.5%) had low titres. In Funtua, 140 samples were collected with 132 (94.3%) recording high titres while 8 (5.7%) had low titres. All samples (100) collected from Shika had high titres (100%). Statistical evaluation with analysis of variance and Tukey's HSD tests showed no significant difference at the alpha = 0.05 level of significance between mean antibody titres in the areas under investigation; this showed the vaccines used during the anti-rinderpest campaign to be of good immunogenic quality. PMID- 8470426 TI - Comparison of conventional adjuvants and 'adjuvant-free' monoclonal antibody targeting for stimulating antibody responses against a conjugate of luteinizing hormone releasing hormone and avidin. AB - A conjugate of luteinizing hormone releasing hormone (LHRH) and avidin was used for immunizing mice and sheep. In mice, a range of adjuvants co-administered with the conjugate was shown to affect antibody titre and isotype. The commercially available Montanide and Ribi adjuvant emulsions, polyadenylic-polyuridylic acid, Quil A and Freund's complete adjuvant all produced high antibody titres to LHRH (reciprocal titre range 8000-20,000) and avidin (range 9000-35,000). Alhydrogel, Pluronic gel, Immunostim, DEAE-Dextran and muramyl dipeptide were weak to moderately effective (reciprocal titre ranges of 1300-5000 for LHRH and 3000-6000 for avidin, respectively). With Quil A, the response to avidin in mice was found to consist of roughly equal proportions of the IgG1, IgG2a and IgG2b isotypes. In contrast, the response to avidin using the other adjuvants and to LHRH consisted predominantly of the IgG1 isotype. An 'adjuvant-free' immunization strategy was attempted by targeting the LHRH-avidin conjugate to class II major histocompatibility complex (MHC) determinants on cells of the immune system. Using an immunoconjugate formed by linking LHRH-avidin to an antibody specific for mouse and sheep class II molecules, a twofold augmentation of titres relative to controls was obtained in mice. These antibodies were almost exclusively of the IgG1 isotype. In contrast, monoclonal antibody targeting in sheep resulted in a significantly enhanced immune response (reciprocal titres of 15,000 and 20,000 for LHRH and avidin, respectively) which was comparable to that achieved by immunizing with Quil A as adjuvant. Both the monoclonal antibody targeting and Quil A treatments tended to favour the production of antibody isotype IgG1 over IgG2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470427 TI - Distinct patterns of T- and B-cell immunity to respiratory syncytial virus induced by individual viral proteins. AB - Mice were infected with respiratory syncytial (RS) virus or with recombinant vaccinia viruses (rVV) expressing individual RS virus proteins. rVV-G, rVV-F and, to a lesser extent, rVV-P induced ELISA-binding anti-RS virus antibodies; those induced by rVV-P were non-neutralizing. Different antigens induced helper T cells with distinct cytokine secretion profiles: some released IL-2, and others predominantly IL-4 and 5. Virus-specific cytotoxicity was induced by infection with RS virus, rVV-F or rVV-22K. Different RS virus proteins (given in the same route and form) therefore prime for functionally distinct T-cell activities. These patterns of virus-specific immunity may help explain the pathogenicity of RS virus vaccines, and help in the design of protective, non-pathogenic vaccines in the future. PMID- 8470428 TI - Vaccination of mice against canine distemper virus-induced encephalitis with vaccinia virus recombinants encoding measles or canine distemper virus antigens. AB - Measles and canine distemper are caused by serologically related viruses. Although dogs immunized with measles virus (MV) do not elicit canine distemper virus (CDV) neutralizing antibodies, they are protected against the fatal disease. To investigate the potential role of the MV antigens in protection against CDV, we have immunized mice with vaccinia virus (VV) recombinants expressing the MV haemagglutinin (HA), fusion (F), nucleoprotein (NP) and matrix (M) antigens and challenged them with CDV. A partial protection was observed with the VV recombinants expressing the F, NP and M antigens, but not the HA. In contrast, immunization with a VV recombinant expressing the CDV F protein completely protected mice from CDV. PMID- 8470429 TI - Serological correlates in whooping cough. AB - Antibody concentrations to three Bordetella pertussis antigens in 94 predisease samples from women who, within a median of 220 days, developed culture-confirmed whooping cough were compared to antibodies in samples from matched controls. The median IgG antibody levels were significantly lower to all three antigens, pertussis toxin, filamentous haemagglutinin and lipopolysaccharide, in the predisease samples of cases as compared to non-cases (p values ranging from 0.0001 to 0.01). A significant difference in antibody distribution was, however, found only to pertussis toxin, measured either by ELISA or by a neutralization test (p values of 0.0004 and 0.007, respectively). The results could be interpreted as meaning that antibodies to the different antigens all participate in protection against disease but that antibodies to pertussis toxin play a major role. PMID- 8470430 TI - An experimental vaccine cocktail for Plasmodium falciparum malaria. AB - Surface proteins from several different life-cycle stages of the malaria parasite Plasmodium falciparum were expressed at high levels in the yeast Saccharomyces cerevisiae. Purified proteins, both individually and in cocktails, were used to immunize mice and goats in conjunction with either Freund's adjuvant or a muramyl tripeptide-based adjuvant. Immune responses were measured by enzyme-linked immunosorbent assays and by the ability of antisera to inhibit (1) the invasion of hepatocytes by live sporozoites, (2) in vitro invasion of human erythrocytes by live merozoites, and (3) the development of oocytes in the mosquito vector. These results suggest that cocktails of different stage-specific antigens can provide the components necessary to block the development of the malaria parasite at multiple stages of its life cycle. PMID- 8470431 TI - Construction of an aroA mutant of Salmonella serotype Gallinarum: its effectiveness in immunization against experimental fowl typhoid. AB - An aroA mutant was produced from a virulent strain of Salmonella Gallinarum, the causative agent of fowl typhoid in poultry, by Tn10 insertional inactivation and deletion. The mutant was highly attenuated for chickens. A single intramuscular immunization of 2-week-old chickens with 10(7) mutant organisms reduced mortality following oral challenge with 10(8) organisms of the parent strain from 63 to 30%. In a second experiment multiple immunizations with 10(8) mutant organisms reduced mortality after challenge with 10(7) organisms of the virulent strain from 77 to 0%. By oral inoculation the mutant was not able to immunize chickens against oral challenge. PMID- 8470432 TI - Proliferative responses to purified and fractionated Bordetella pertussis antigens in mice immunized with whole-cell pertussis vaccine. AB - The specificity of the cell-mediated immune response to Bordetella pertussis following immunization of C57B1 mice with a whole-cell pertussis vaccine was assessed in a proliferation assay. A proliferative response of lymph node lymphocytes to the filamentous haemagglutinin, the 69 kDa outer membrane protein and the agglutinogens 2 and 3 was demonstrated. The proliferative cells were T cells of the CD4+ phenotype. In addition, several as yet uncharacterized antigens expressed by B. pertussis were shown to induce a proliferative response, also mediated by T cells of the CD4+ phenotype. Although a range of different immunization schedules and preparations of pertussis toxin were used, no specific proliferative responses to pertussis toxin, which is regarded as a protective antigen of major importance from B. pertussis, were found. PMID- 8470433 TI - Immunogenicity and pathogenicity of a triple temperature-sensitive modified respiratory syncytial virus in adult volunteers. AB - The immunogenicity and pathogenicity of a strain of respiratory syncytial (RS) virus modified by sequential induction of three temperature-sensitive (ts) mutations have been evaluated by intranasal administration to 22 adult volunteers. This modified virus, a triple ts mutant designated ts1C, was derived from a double mutant ts1B evaluated in a previous trial. The original isolate (strain RSS-2) and all its derivatives were propagated throughout in human diploid cells in a specially assigned laboratory. The triple mutant ts1C is unable to multiply in MRC-5 cells at 37 degrees C and above. Following nasal administration of ts1C, immune responses were observed in volunteers with low pre existing neutralizing antibody titres. The ability of mutant ts1C to induce upper respiratory tract disease in adults was greatly diminished in comparison with the non-ts wild-type virus, but not markedly more so than a previously tested double ts mutant (ts1B) which replicates at 37 degrees C. Mutant ts1C, however, may have greater potential as a live vaccine in view of its inherently greater genetic stability. PMID- 8470434 TI - Discordance in the determination of non- or low-responders to HBV vaccine using IMx-AUSAB or AUSAB-RIA. PMID- 8470435 TI - Loss of anti-HBc antibodies after HBV infection in immunized Senegalese children. PMID- 8470436 TI - Anterior sacral meningocele and Marfan syndrome: a review. AB - Anterior sacral meningocele is a not rare entity. Treatment is usually surgical and consists in a transacral posterior approach with patching of the communication between the malformation and the dural sac. But surgery can be difficult and require multiple procedures. We report the first case of a giant anterior sacral meeningocele rapidly cured by a simple endoscopic procedure. We believe that more attention should be used in the diagnosis of such cases as they can be so easily cured. We have reviewed the literature about anterior sacral meningocele and particularly its treatment and its association either with Marfan syndrome or a familial occurrence. PMID- 8470437 TI - Nonparasitic abdominal serous cysts. A multiple case report. AB - A group of 35 patients with nonparasitic abdominal serous cysts is reviewed in order to investigate the diagnostic and therapeutic features of these rare conditions. In most cases the cysts were localised in the liver. Other localisations were the kidney (9 cases), the mesenteric area (2 cases), the adrenals (2 cases), the spleen and the pancreas (one case each). The clinical symptoms were essentially determinated by the size of the cysts, regardless their visceral localisation. Ultrasonography was the most efficient procedure for their detection, although this method's precision for the visceral localisation of the cysts was not entirely reliable (6 errors). The low incidence of such abnormalities as well as the absence of any relevant diagnostic elements for establishing the nonparasitic character of the cysts, favoured the confusions with nonproliferous hydatid cysts, especially in cases of solitary cysts (7 patients). The most frequently used surgical procedures were partial cystectomy (18 cases) and total cystectomy (8 cases). A personal technique based on obliteration of the cavity with the bulging wall of the cysts, was used in two patients. When choosing the surgical procedure, the size, site and number of cysts were considered. Immediate and late postoperative results were very good. PMID- 8470438 TI - Chronic anemia secondary to side-to-side distal small bowel anastomosis. AB - Occult intestinal bleeding was diagnosed in a patient who underwent a distal small bowel resection. The resection was required for small bowel obstruction. She developed iron deficiency anemia four years later. Clinically she presented with melena. Colonoscopy, gastroscopy were unsuccessful in making the diagnosis. But a 99 mass Technetium (99m Tc) Labeled Red Blood Cell (RBC) scintigraphy, established the bleeding site in the gastrointestinal tract. Laparotomy identified an ulcerative lesion at the surgical side-to-side anastomosis. Histology demonstrated focal ulceration with chronic inflammation but did not show crypt abscesses, or granulomata. Medical therapy, including iron and Histamine-antagonists were ineffective. She was treated with resection of the anastomosis. Gastrointestinal bleeding due to anastomotic ulceration appears to be a late complication of small bowel resection with side-to-side anastomosis. PMID- 8470439 TI - Association of aortic stenosis and gastrointestinal bleeding (Heyde's syndrome). Report of two cases. AB - The association between aortic stenosis and digestive angiodysplasia has been described for the first time by Heyde in 1958. This entity is thus known as Heyde's syndrome. In many instances, the recurrent small intestinal bleeding originating from angiodysplasia stopped after aortic valve replacement. We report two cases of patients presenting with a recurrent small intestinal bleeding originating from digestive angiodysplasia and suffering from aortic stenosis. Diagnosis of both pathologies is well documented in both cases. The replacement of the aortic valve by a biologic prosthesis stopped the bleeding. Prior to aortic valve replacement, the two patients suffered severe recurrent blood loss from intestinal angiodysplasia. The treatment of aortic stenosis greatly favored both cardiac and general status. We recommend aortic valve replacement with a biologic prosthesis prior to intestinal resection in patients presenting with Heyde's syndrome. We stress on the fact that anticoagulants must be stopped in order to minimize the risk of further bleeding. PMID- 8470440 TI - Variant form of popliteal artery entrapment syndrome. AB - A forty-six-year-old, non smoker, patient presented with an intermittent claudication of the right calf, clinically compatible with a low popliteal artery obliteration. Arteriography showed an irregular intercondylar popliteal artery and oblitered low popliteal and anterior tibial arteries. Surgical posterior access showed a faulty insertion of the mediate gastrocnemius caput responsible for popliteal artery entrapment syndrome and for aneurysmal dilatation of the popliteal artery above compression. As far as we know, this form of popliteal artery entrapment syndrome has not been published yet. PMID- 8470441 TI - Use of tissue expansion in head and neck. Review of 33 cases. AB - Thirty-three patients have had skin expansion for reconstruction in the head and neck area. Expansion was used alone in 21 patients, and combined with other techniques in 12 patients. Indications, operative technique, complications and failures of the method are discussed. PMID- 8470442 TI - Benign tumours of the upper gastro-intestinal tract (stomach, duodenum, small bowel): a review of 178 surgical cases. Belgian multicentric study. AB - The results of retrospective series counting 178 cases of surgically resected stomach, duodenum and small bowel benign tumours are analysed. It is a Belgian retrospective multicentric study that extend over a mean duration of 7 years 9 months. The main symptoms are haemorrhage, dyspepsia, obstruction and invagination. The most frequent tumours are leiomyoma, adenomatous polyps, lipoma and schwannoma. Preoperative investigations are endoscopy and radiology. To finish off the gastro-duodenal tumours examinations, endoscopy is necessary and arteriography can be helpful in small bowel tumours. Operative mortality of this series is 2.2%; local and general postoperative complications are 34.2%. Observed local recurrence in 118 patients with mean follow-up of 27 months is 1.7%. The authors emphasize the surgical resection necessity of these tumours as their malignant potentiality is not inconsiderable. Considering local recurrence, malign change and afar dissemination, a long-term follow-up is recommended. PMID- 8470443 TI - Intermittent gallstone ileus following endoscopic biliary sphincterotomy. A case report. AB - A 72-year-old woman presented with periods of colicky abdominal pain following endoscopic sphincterotomy and lithotripsy for choledocholithiasis. A diagnosis of intermittent gallstone ileus was made, while it appeared that a large gallstone, that was not removed from the common bile duct, obstructed the small bowel. The intermittent course was elicited by pendulation of a gallstone between two stenoses, which originated from chronic radiation enteritis. PMID- 8470444 TI - Selective rupture of the Wirsung duct: a rare form of pancreatic trauma. AB - A patient with a traumatic pancreatic lesion, confined to the Wirsung duct, is presented. At first laparotomy, the diagnosis was missed. Posttraumatic acute pancreatitis led to endoscopic pancreatography, disclosing the exact localization of the lesion. Left pancreatectomy led to rapid recovery. A late postoperative pancreatic fistula healed without problems. PMID- 8470445 TI - Atraumatic splenic rupture in the course of a pneumonia with Streptococcus pneumoniae. Case report and literature review. AB - Atraumatic splenic ruptures in the course of infectious diseases are rare but have been reported. Various germs of viruses can be at the origin of such rupture. The more often quoted viral disease is infectious mononucleosis. The more frequently involved bacteria are Streptococcus non pneumoniae, Pseudomonas, staphylococci and Clostridium. Rupture mechanism is not clearly elucidated; it can be connected with sepsis diffusion at spleen level via haematogenic way and consequently splenomegaly. Splenic rupture following septicaemia does not always entail major splenomegaly nor abscess formation but the attack of the splenic tissue itself is sometimes sufficient to bring about the rupture. The present case of atraumatic splenic rupture on spleen sepsis, no abscess, starting from a pulmonar infection with Streptococcus pneumoniae is, to our knowledge, the first case reported in literature. PMID- 8470446 TI - Splenic aneurysm rupture. Case report and review of the literature. AB - The authors report a case of splenic aneurysm rupture in a 61-year-old woman. The diagnosis was made by computed tomography in the second phase of a "double rupture phenomenon" in circulatory collapse. This was successfully treated by aneurysmectomy and splenectomy. The case is reported together with the literature review. PMID- 8470447 TI - Intestinal obstruction and portal vein gas embolism. AB - The presence of hepatic portal vein gas is the consequence of invasion by anaerobic bacteria originating from an intestinal tract lesion. Although this phenomenon is rare, it may result from several common intestinal pathologies. The prognosis, despite intensive treatment, is often very poor. The authors report a case associated with bowel necrosis resulting from intestinal band. PMID- 8470448 TI - Treatment of colon endoscopic perforations. AB - We describe the treatment of 9 patients who underwent endoscopic perforation of the large bowel. All perforations occurred in patients with colonic diverticulosis or during polypectomy. The choice between conservative or surgical management essentially depends on clinical criteria. Conservative treatment, clinical observation, broad spectrum antibiotics and parenteral diet, is recommended for patient in good general condition and without any sign of peritoneal irritation. Free intraperitoneal gas on X-ray is not an indication for laparotomy. On the other hand, the development of peritonism or clinical deterioration under medical treatment requires a surgical management. Primary suture of the perforation can be performed if the colon was well cleansed for colonoscopy, if the perforation is small and if there is no suspicion of underlying carcinoma. In the other cases, resection including the perforation must be recommended. PMID- 8470449 TI - Pulmonary actinomycosis. Case report. AB - Pulmonary actinomycosis. Case report. Pulmonary actinomycosis is a rare infectious disease. The major difficulty is mainly the diagnosis. A high dose of suspicion is required in each intrathoracic process showing malignant behaviour, despite benign histology. Especially if the process extends through normal tissue planes, actinomycosis should be suspected. The therapy of choice should consist in high dose of antibiotics for several months, occasionally followed by surgery. Often though, surgery is the first treatment because of the unability to differentiate the lesion from malignant tumor. Surgery should always be followed by long term antibiotic therapy. PMID- 8470450 TI - The global design of the hindlimb in quadrupeds. AB - In the hindlimb of quadrupeds three major segments can be distinguished which can rotate with respect to each other in the hip, knee and ankle joints. Movements in a sagittal plane appear to be controlled by three sets of antagonistic mono articular muscle groups (one set per joint) and two sets of antagonistic bi articular muscles. This design allows co-activations of mono-articular agonists and their bi-articular antagonists. These co-contractions occur for example in ballistic tasks such as jumping where the transfer of angular acceleration in the joints into the translational acceleration of the hip decreases as a function of joint extension. Well-trained humans appear to solve this problem by a distinct proximodistal sequence in the timing of the joint extensions and a transport of energy via bi-articular muscles. This can also be observed in a number of animals. A second example has to do with the necessity for a certain distribution of net moments in the joints which is required to control the direction and magnitude of the external force on the ground. The control of these moments can to a large extent be judged as a requirement which is independent of the joint displacements required in the same task. Many walking, running or pulling tasks, for example, require knee extension combined with a net knee flexing moment. Co activation of mono-articular agonists and their bi-articular antagonists appear to solve these problems in an effective and efficient way. PMID- 8470451 TI - Comparison of the damping effect of different shoeing by the measurement of hoof acceleration. AB - The purpose of this study was to compare the damping effect of 16 types of shoeing by measuring hoof acceleration parameters on two trotting horses. At impact, maximal deceleration had extreme values such as 188 m/s2 (+/- 55) for the most damping combination (p < 0.01) and 746 m/s2 (+/- 14) for the steel shoe (mean = 551 m/s2 +/- 125). After the shock, the hoof was exposed to a mean vibrating acceleration at 418 Hz (+/- 84) which was progressively damped in 37.3 ms (+/- 10.5). According to these results, the damping ability of different farriery products significantly reduces (p < 0.05) shocks and vibrations at hoof impact in the athletic horse caused by runs on asphalt or similar surfaces. In practice, the use of the most efficient shoeing should help to reduce the incidence of the over-used joint diseases in the athletic horse caused by runs on hard surfaces. PMID- 8470452 TI - Concept of a force-measuring horseshoe. AB - To further develop objective methods in the field of gait analysis a force measuring horseshoe (FM shoe) has been developed. The ground reaction forces were determined by measuring the degree of displacement between the two solid parts of the shoe. This was done by three removable measuring units (MUs) that were equipped with strain gauges and placed in the toe and in each of the quarter parts. Before performing force recordings the sensors were calibrated with the actual MUs mounted on the shoe. This can be done in the field with a specially developed equipment. The shape of the signal generated by the MUs corresponds very well to signals generated by other instrumented shoes and force plate traces reported by other authors. In a comparative study between the FM shoe and a force plate a good resemblance between force traces from the two systems was seen. There is still some work to be done to refine the method of calibrating the FM shoe. However, the good linear relationship between forces applied and the sensor signals implies that the concept of the FM shoe will fulfill the requirements of measuring absolute forces. PMID- 8470453 TI - A method to estimate the initial length of equine tendons. AB - A procedure is described by which the length of a tendon at the onset of loading is determined objectively. The procedure includes the fitting of third-order polynomial functions on the load-elongation data. The onset of loading is detected by an increasing fit of the polynomial by selective data reduction of the initial part of the load-elongation curve. The procedure results in an objective and reproducible definition of the zero strain level of a tendon. PMID- 8470454 TI - Measurement techniques in animal locomotion analysis. AB - Animal performance can be determined by subjective observations or objective measurements. Numerical data are only then superior to results of subjective observations when they are the result of measurements carried out to test a well defined hypothesis or to give the answer to a clear, precisely formulated question. In the analysis of kinematics a careful evaluation of the set-up of the measurement equipment and the resulting accuracy in the data is required. Measurements in three dimensions (3D) are theoretically better than those in 2D. Practically, however, collection, analysis, interpretation and presentation of 3D data are so much more complicated that frequently 2D analysis appears to be more useful. The minimal size of markers necessary to obtain a certain accuracy in kinematic data is usually too big for practical use. Smaller markers impair accuracy. Reduction of measurement noise is obligatory when time derivatives are to be calculated. Skin movement artefacts cannot be removed by data smoothing. Forces occurring between the digits and the ground can be determined using a force plate or an instrumented shoe. A force plate is accurate, but repeated trials are necessary. Using a force shoe each ground contact results in useful data. However, the shoe itself may affect locomotion. Surface strains on long bones can be recorded relatively easily. Determination of loading forces from surface strains is complicated but can be carried out using multiple strain gauges and a post-mortem calibration test. Strain in tendons is difficult to measure due to problems in defining a'zero' or reference length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470455 TI - Recommended terminology for researchers in locomotion and biomechanics of quadrupedal animals. AB - This paper summarizes recommendations for terminology to be used in the description of quadrupedal locomotion and selected aspects of biomechanics. Directional terms and planes of the body (anatomical position, spatial reference systems), joint angulation, conformation, general locomotion terminology, phases of the stride and limb cycle (e.g. step, cadence) and terminology for the description of jumping are described. PMID- 8470456 TI - Application of TrackEye in equine locomotion research. AB - TrackEye is an analysis system, which is applicable for equine biokinematic studies. It covers the whole process from digitizing of images, automatic target tracking and analysis. Key components in the system are an image work station for processing of video images and a high-resolution film-to-video scanner for 16-mm film. A recording module controls the input device and handles the capture of image sequences into a videodisc system, and a tracking module is able to follow reference markers automatically. The system offers a flexible analysis including calculations of markers displacements, distances and joint angles, velocities and accelerations. TrackEye was used to study effects of phenylbutazone on the fetlock and carpal joint angle movements in a horse with a mild lameness caused by osteo-arthritis in the fetlock joint of a forelimb. Significant differences, most evident before treatment, were observed in the minimum fetlock and carpal joint angles when contralateral limbs were compared (p < 0.001). The minimum fetlock angle and the minimum carpal joint angle were significantly greater in the lame limb before treatment compared to those 6, 37 and 49 h after the last treatment (p < 0.001). PMID- 8470457 TI - Quantification of the locomotion of Dutch Warmblood foals. AB - To get an in-depth insight into the ontogeny of the equine locomotor apparatus, the locomotion of 28 Dutch Warmblood foals was recorded at the walk, trot and canter on a treadmill using a CODA-3 apparatus. A great similarity in joint angle time diagrams was found, although considerable differences in kinematic gait parameters of individual foals could be detected. These results contribute to an objective comparison of the locomotor performance of foals. PMID- 8470458 TI - Surface strain on the dorsal metacarpus of thoroughbreds at different speeds and gaits. AB - Stacked rectangular rosette strain gages were used to measure surface bone strain on the dorsomedial cortex of the third metacarpal bones in 6 adult Thoroughbred horses during treadmill exercise. The peak principal compressive and tensile strains, angle of the peak strains and strain rate during loading were calculated and compared with speed and gait. At speeds from 4 to 14 m/s loading on the metacarpus resulted in compression of the dorsomedial cortex. Tension only occurred consistently in 1 forelimb of 1 horse at the walk (2 m/s). The angle of peak compression was within 10 degrees of the longitudinal axis of the bone, and the magnitude of compression was proportional to the speed of exercise. Mean maximum compressive strains in the 6 horses at 2 m/s were -668 mu strain, -1,204 mu strain at 4 m/s; -1,617 mu strain at 6 m/s; -2,127 mu strain at 8 m/s, and 2,533 mu strain at 10 m/s. Recordings from 3 horses gave a mean -3,206 mu strain at 12 m/s, and strains at 14 m/s approached -4,000 mu strain. Peak strains were similar in both forelimbs at the canter while strain rate tended to be higher in the leading forelimb. PMID- 8470459 TI - Kinematics of the standardbred trotter measured at 6, 7, 8 and 9 m/s on a treadmill, before and after 5 months of prerace training. AB - A kinematic study was performed on a group of 8 Standardbred stallions. Recordings were done using a modified CODA-3 optoelectronic kinematic analysis system with the horses running on a treadmill at speeds of 6, 7, 8, or 9 m/s. Linear and temporal gait characteristics, joint angle diagrams and the trajectories of the hoof in a plane perpendicular to the direction of movement were studied. Two consecutive recording sessions were held at an age of 21-23 months, and a third was held 5 months later after an intensive training period. Joint angle diagrams appeared to show a similar pattern for all horses though certain individual characteristics could be identified. Only a few kinematic parameters appeared to have significantly changed after the 5-month training period (p < 0.05). The hoof trajectories showed marked and consistent differences between front and hind hooves, but the most striking feature was the very individual character of the patterns exhibited, leading to the assumption that these patterns could possibly be used as the 'fingerprint' of the horse. PMID- 8470460 TI - In vivo tendon forces in the forelimb of ponies at the walk, validated by ground reaction force measurements. AB - The load distribution over tendinous structures in the equine forelimb was studied by computing forces from in vivo signals of implanted liquid-metal strain gauges in 5 ponies. For validation, these tendon forces were converted to joint moments, which were summed and compared to the calculated joint moments caused by the ground reaction force. Mean peak forces per kilogram body weight (n = 5) amounted to 5.2 N/kg for the superficial digital flexor tendon, 3.8 N/kg for the deep digital flexor tendon, 7.3 N/kg for the distal accessory (check) ligament and 8.4 N/kg for the third interosseous muscle (suspensory ligament). The maximal moment exerted by the tendons about the fetlock joint differed 11 +/- 7% (average +/- SD, n = 5) from the maximal ground reaction force moment, which difference amounted to 17 +/- 15% for the coffin joint moments. These differences appeared to result to a substantial extent from errors in the moment arms. Therefore, the computed tendon forces were considered to be sufficiently reliable. PMID- 8470461 TI - Gallop kinematics of Olympic three-day event horses. AB - Limb contact variables of the gallop of 3-day event horses were determined for competitors in the 1988 Seoul Summer Olympic Games. Horses were filmed during the steeplechase, phase B of the speed and endurance test on day 2 of competition. Two 16-mm high-speed cameras were aimed perpendicularly to the direction of subject motion along a straightaway on the steeplechase track, filmed at 200 frames/s. Thirty-four of 48 competitors were filmed and 108 gallop strides analyzed. Velocity (VEL) averaged 12.09 +/- 0.10 m/s (mean +/- SE), stride length (SL) 6.04 +/- 0.05 m and stride frequency (SF) 2.00 +/- 0.01/s. Superior overall 3-day event performances were associated with faster VEL and longer SL in the steeplechase phase. A linear and quadratic regression of SL and SF against total 3-day penalty points yielded a response surface revealing that the score was optimized with gallop SF between 1.85 and 2.05/s and VEL between 13 and 14.3 m/s. Up to 7 m, there appeared to be no upper limit for optimal SL. This study provided objective documentation of gallop stride kinematic patterns associated with successful performance in world-class 3-day event competition. PMID- 8470462 TI - Determination of the center of pressure of the hoofs of the forelimbs of horses standing on a flat level surface. AB - The pressure exerted on a flat level surface by recently trimmed, unshod hoofs of the front limbs of 23 sound, adult horses was measured using pressure-sensitive film and a specially built cassette. The horses were tranquilized and stood with one foot on the 2.9-cm-thick cassette and the other on a block of equal height. The hoofs were observed for motion during the measurement, and the developed film was examined for improper alignment of the film or slipping of the hoof. The center of pressure was located using the method of weighted proportions of Barrey. This static measurement system with a long measurement time and the number of measurements reduced the influence of variables inherent in the horses' behavior and the measuring system. The calculated point was recorded as falling medial to, lateral to or on a line bisecting the central sulcus of the frog. In the dorsal to palmar orientation the point was classified with reference to a line drawn halfway between the most dorsal and the most palmar mark on the film. Forty-six percent of the calculated centers of pressure were located in the medial heel area. Binomial analysis for large samples indicates that this was a significant variation from a random distribution. Seventy-six percent of the centers were located in or on the borders of the medial heel. PMID- 8470463 TI - A preliminary study of transitions between the walk and trot in dressage horses. AB - The object of this study was to determine the limb support sequence during the transitions from walk to trot and from trot to walk in dressage horses under saddle and to test the null hypothesis that the limb support sequence during the transitions is not related to the level of training. Sixteen dressage horses training at novice to FEI Grand Prix level were videotaped performing an average of 9 transitions each from walk to trot and from trot to walk. The 30-Hz videotapes were viewed in slow motion, and based on the limb support sequence the transitions were categorized into two types. In type 1 transitions there were no intermediate steps between the walk and trot sequences. Type 2 transitions were characterized by intermediate steps, including a single support phase. The Kendall rank-order correlation coefficient showed that a higher level of training was positively associated with an increased percentage of type 1 transitions for both walk-to-trot transitions (p < or = 0.05) and trot-to-walk transitions (p < or = 0.01). No significant preference for initiating or completing the trot on the left or right diagonal was found using the binomial test for individual horses and the Wilcoxon signed-ranks test for the group. PMID- 8470464 TI - The extended canter: a comparison of some kinematic variables in horses trained for dressage and for racing. AB - This study was designed to test the hypothesis that there is no significant difference in selected temporal and linear stride variables of the extended canter in horses bred and trained for dressage or racing. Nine advanced-level dressage horses and 7 Thoroughbred racehorses were filmed at a frame rate of 200 Hz at an extended canter on a sand track. Two strides were recorded per trial, and each horse performed 6 or 7 trials. Temporal and linear data were determined from the films, and descriptive statistics (mean, SD) were calculated. Strides were selected for analysis on the basis of having a velocity in the range of 6.0 7.0 m/s, and multivariate analysis of variance was used to detect significant differences in the stride kinematics of horses trained for the two sports (p < or = 0.01). The average velocity of the dressage horses was 6.37 m/s, compared with 6.40 m/s for the racehorses. There were no significant differences between the two groups in velocity, stride duration, stride length or the distances between limb placements. The stance durations of all four limbs and the overlaps between them were longer, whereas the duration of the suspension phase was shorter in the dressage horses than in the racehorses (p < or = 0.01). The time between impacts of the diagonal limb pair was close to zero in both groups, with individual horses showing some variability in the order of placement of the diagonal limb pair. However, the sequence of footfalls was not significantly different between the two groups (p < or = 0.01). PMID- 8470465 TI - In vivo measurements of the loading conditions on the tibia of the goat. AB - In vivo strain measurements at 8 locations on the tibia of the goat were performed. Successive in vitro calibrations were used to determine the assumed linear relationship between the measured strain signals and the external loads (3 forces and 3 moments) at the tibia. For the reconstruction of the in vivo external loads from the strain data, a transformation matrix was created from the calibration experiments, using 'singular-value decomposition'. The method is a reliable technique for measuring in vivo loads during functional gait and gives reproducible results. PMID- 8470466 TI - Shortening of the forelimb in the horse during the stance phase. AB - Compressions in the forelimb of a horse trotting at 3.7 m/s were studied using high-speed cinematography. From a diagram of shortenings it has been concluded that successive loadings in the longitudinal direction from below signify longer impact time and smaller impact forces compared to a theoretically stiff limb. It is proposed that the limb takes up the impact force passively until the onset of loading at the elbow joint, i.e. 30 ms following first contact. PMID- 8470467 TI - Quantification of hind limb lameness in the horse. AB - The three-dimensional optoelectronic locomotion analysis system SELSPOT II was used for kinematic studies of hind limb locomotion patterns. Two groups, 11 sound horses and 15 horses suffering from hind limb lameness, were examined at the trot. Both graphical and quantitative analyses were compared in sound and lame horses. The parameter hip acceleration quotient (HAQ), using the different peaks of vertical acceleration of one hip during one stride, proved to be a suitable value for quantitative analysis of hind limb lameness. In sound horses the HAQ ranged from 1.03 to 1.54, lame horses showed values between 1.32 and 2.96. Checking and documentation of diagnostic anesthesias or therapies are possible applications. PMID- 8470469 TI - First (ESB) workshop on animal locomotion. Utrecht, The Netherlands, June 20-22, 1991. Proceedings. PMID- 8470468 TI - Relationship between locomotor forces, hoof position and joint motion during the support phase of the stride of galloping horses. AB - Three methods were used simultaneously to determine the relationships between the vertical forces exerted on the hooves and the positions of the limbs and hooves at the times of peak vertical forces from 2 horses galloping on a track straightaway. Vertical forces were recorded from an instrumented shoe, fetlock joint motion was measured with an electrogoniometer and the angles of the carpus, fetlock and hoof were determined from slow-motion films. At hoof contact, the mean angles of the carpus and fetlock were 181-182 degrees and 199-206 degrees, respectively. Peak vertical forces on the heel occurred at or near maximum extension of the carpal and fetlock joints. Peak forces on the toe occurred during flexion of the fetlock joint and at mean hoof angles of 28-31 degrees from the horizontal. The mean angles of the hoof from the horizontal at the time of heel contact were 6-7 degrees. Hoof lift occurred at mean carpal angles of 173 174 degrees and mean fetlock angles of 199-200 degrees. PMID- 8470470 TI - Kinematic gait analysis in equine carpal lameness. AB - Gait analysis plays a major role in the clinical evaluation of equine lameness. It is generally accepted that the clinician expresses the grade of lameness as a subjective score. In this study lameness was objectively assessed using a standardized transient lameness model, in which lameness was induced by intra articular injection of bacterial endotoxin into the radiocarpal joint of ponies. Lameness was scored by an experienced clinician, and locomotion was recorded simultaneously using a CODA-3 apparatus. The obtained kinematic gait parameters correlated well with the clinical lameness score and also provided possibilities to objectively study the locomotor disturbances of the lame limb in more detail at the walk and trot. PMID- 8470471 TI - Stride characteristics of overground versus treadmill locomotion in the saddle horse. AB - The purpose of this study was to compare the velocity-dependent changes in stride length and stride frequency of horses performing the same incremental exercise test first on a track with a rider and then on a treadmill with a 0 and 3.5% slope successively. Seven French saddle horses undertook the exercise test which consisted of 5 stages of increasing speed for 3 min each with 1 min rest between each stage (1.6, 4.2, 8.3, 9.2 and 10 m/s). The horses were recorded by use of a video camera, and the tapes were analysed with regard to gait parameters. At 1.6, 8.3, 9.2 and 10 m/s, stride frequencies were significantly (p < 0.01) greater on the track than on the treadmill. At the walk, stride length was significantly (p < 0.01) shorter on the track than on the treadmill. There were strong linear relationships between stride length and speed in all experimental conditions (R2 > 0.96). The comparison of the regression coefficients revealed significant differences (p < 0.01) between track and treadmill locomotion; stride length was longer on both the horizontal and inclined treadmill than on the track. The incline of the treadmill did not significantly (p > 0.01) influence stride parameters. PMID- 8470473 TI - Vestibular neuronitis. Proceedings of an international symposium on vestibular ganglia and vestibular neuronitis. Yamaguchi, Japan, 14-16 September, 1991. PMID- 8470472 TI - Multi-body modelling and simulation of animal locomotion. AB - Multi-body models of musculoskeletal systems can be used to determine internal forces from measured external forces and movements ('inverse dynamics') and to perform simulations of movements using muscle forces or activations as input ('direct dynamics'). Examples of 'direct' simulations of movements in the horse are presented. With a model of the equine hindlimb, the function of the 'passive stay apparatus' could be explained. A model of the forelimb was used to determine force distributions in the digital flexor tendons, and to experiment with various methods to change the force distribution. Simulations of this type are valuable tools in basic research on functional anatomy and aetiology of injuries. An application with much future potential is the optimization of sports performances using simulation methods. PMID- 8470474 TI - Contribution of the vestibular primary neuron and the sensory cell to posture recovery. AB - The right vestibular nerve of the frog was cut peripherally to the vestibular ganglion. The frog sustained a tilting posture toward the right side. This tilting disappeared and the frog returned to normal posture. Based on this finding, the following experiments were done: In experiment I, the right vestibular nerve was again cut after posture recovery. The tilting angle was smaller and the recovery period shorter than after the 1st neurectomy. In experiment II, the left nerve was cut after posture recovery. The tilting angle toward the left was greater than that of the 1st neurectomy. In experiment III, the frog underwent bilateral neurectomy. A piece of the bone was inserted into the cut ends of the right nerve to inhibit nerve regeneration. The frog slowly developed tilting toward the right side. The above results indicate that both reactivation of the endorgan and the central compensatory mechanism play essential roles, for postural recovery after vestibular neurectomy. PMID- 8470475 TI - Vestibular pathology of totally deaf ears. AB - The temporal bone vestibular pathologies of 23 totally deaf ears (16 patients) were studied. Abnormal findings in the saccule were seen more often than in the other vestibular sensory organs. Abnormal findings in the vestibular ganglion cells were found in 7 ears. There were fewer ears with main damage in the hair cells than with main damage in the nerves. PMID- 8470476 TI - Glial fibrillary acidic protein (GFAP)-like immunoreactivity in the vestibular endorgan of the rat. AB - The distribution of glial fibrillary acidic protein (GFAP)-like immunoreactivity in the peripheral vestibular nervous system of normal adult rats was studied using immunohistochemical methods. The immunoreactivity was demonstrated at the light-microscopic level. GFAP-like immunoreactivity could be seen at the vestibular fibers terminating in the hair cells. PMID- 8470477 TI - Characterization of the vestibular and spiral ganglion cell somata of the rat by distribution of neurofilament proteins. AB - Neurons of the spiral and vestibular ganglia of the adult rat were labelled with a panel of monoclonal and polyclonal antibodies which were raised against different subunits of neurofilament proteins (NFPs). Thirteen antibodies labelled intensely the perikarya of a distinct group of somata in both the spiral and vestibular ganglia while the majority of somata were unreactive or showed a weaker reaction. The distinction between intensely immunostained and other cell somata was more conspicuous in the spiral than in the vestibular ganglia. Intensely stained somata formed a subpopulation comprising about 9% (range from 7.2 to 11.1%) in the spiral and about 32% (range from 21.2 to 36.4%) in the vestibular ganglia of the total ganglion cell population. Antibodies against different subunits of NFPs seemed always to stain the same somata. In morphometric analysis the mean diameters of intensely labelled spiral ganglion cells were clearly smaller (9.9 microns) than those of the slightly reactive cells (11.9 microns). In Scarpa's ganglia the intensely reactive cells were larger in size (mean diameter 21.4 microns) than the slightly reactive cells (mean diameter 14.7 microns). In the spiral ganglia, the intensely labelled group of neurons seems to correspond to the morphologically distinct type II cells which may also functionally differ from type I cells. In Scarpa's ganglia, the intensely stained subgroup of somata may correspond to the large neurons innervating central regions of cristae and maculae. Their functional significance remains to be elucidated. PMID- 8470478 TI - Clinical observation of 32 cases of vestibular neuronitis. AB - Clinical observations were made on 32 patients with vestibular neuronitis in the last 5 years: 14 male and 18 female, ranging from 15-76 years, the average being 46.3. Within the age distribution of the cases, two peaks were observed: a younger and an older group. Five patients (15%) had recently contracted infection of the upper respiratory tract before the onset of the disease, and two developed benign paroxysmal positional vertigo during the recovery period. Spontaneous nystagmus was observed in 19 cases (59%) in the first medical examination. There were several patients in whom there was the possibility of central lesions based upon the findings of equilibrium examinations. No relation was found between the degree of canal paresis and the time required for recuperation; however, the older patients took much longer to recover from the disease. Our results showed that there were considerable individual variations regarding the clinical findings, which may suggest that the pathological entity that creates this disease is not simple. PMID- 8470479 TI - Light and electron microscopic features of the rat vestibular ganglion cells. AB - The vestibular ganglion cells of the rat were characterized with regard to the cytoplasmic structure by light and electron microscopic observation. Light microscopy revealed four types of cells, depending upon the characteristics and distribution of Nissl granules. Electron microscopy gave a definite classification of these types by the arrangement and distribution of the roughly surfaced endoplasmic reticulum and neurofilament. The characteristics of the ganglion cells are discussed in relation to their size and function. PMID- 8470480 TI - 3-D anatomy of Scarpa's ganglion and surrounding structures. AB - We reconstructed in three dimensions, and measured by a computer-aided method developed by us, Scarpa's ganglion and surrounding important anatomical structures in 7 normal human temporal bones obtained from 7 individuals aged 7 days to 72 years. We found that this ganglion is shaped like an hourglass and lies with its superior part directed anterosuperolaterally, and its inferior part posteroinferomedially; these two parts are connected by the isthmus ganglionaris. Although the dimensions of the parts of the ganglion varied, such a structure was distinguishable in all the specimens we studied. The volume of the ganglion was found to be relatively consistent in these postnatal specimens; although the width and height of the ganglion varied, they were inversely correlated with each other (linear regression analysis, p < 0.05). We did note, however, some postnatal increase in the distance from the ganglion to its neighboring structures. We also identified a significant correlation between the width of the ganglion and the length of the internal auditory canal and the distance from the ganglion to the vestibular endorgans in any given specimen (linear regression analysis, p < 0.05). These results suggest that although the volume of Scarpa's ganglion does not change after birth, its shape does change with the growth of the individual temporal bone. PMID- 8470481 TI - Three-dimensional observation of the Golgi apparatus in the vestibular (Scarpa's) ganglion cell. AB - Ultrastructure of the Golgi apparatus and GERL was observed three-dimensionally from the functional view point of lysosome formation. GERL directly continues with rough endoplasmic reficulum. There are at least two systems for lysosome formation, i.e. dependent and not dependent systems on the Golgi stack respectively. GERL also continues with a trans Golgi saccule, indicating that GERL is a part of the Golgi apparatus. PMID- 8470482 TI - Audiovestibular findings in patients with vestibular neuritis: a long-term follow up study. AB - During the years 1980-1981, 19 patients with a mean age of 39 years, given the diagnosis vestibular neuritis were subjected to a caloric bithermal test, a pure tone audiogram and stapedius reflex measurements within 1 week, 3 weeks, 9 weeks and 1 year after the onset of symptoms, respectively. In a majority of the patients the feeling of dysequilibrium and vertigo diminished within the first 3 weeks and the difference in caloric reaction between the two sides also diminished during this period. In 9 of the patients, a uni- or bilaterally elevated stapedius reflex threshold was found. The return of the caloric response was somewhat slower in this group of patients. PMID- 8470483 TI - Three-dimensional reconstruction of the Golgi apparatus and the endoplasmic reticulum of the vestibular ganglion cell. PMID- 8470484 TI - Ultrastructure of the chick vestibular ganglion and vestibular nucleus. A scanning electron microscopic study. AB - The fine structure of the chick vestibular ganglion and vestibular nucleus was studied in three dimensions using a scanning electron microscope (SEM). NaOH and OSO4 maceration methods were applied to observe the configuration in the mechanically torn specimens. Also, Tanaka's aldehyde prefix OSO4-DMSO-OSO4 method (A-O-D-O method) was applied to observe the intracellular structure in the fractured specimens. The surface of the ganglion cell and the nerve processes were seen to be covered with abundant thin fibrous tissues in the specimen treated with OSO4 maceration. This surface fibrous tissue was completely removed with the NaOH maceration method. As a result, the ganglion cell and nerve processes could be seen to be enveloped in the myelin sheath. In the fractured vestibular ganglion treated by the A-O-D-O method, there were three patterns of perikaryal myelination in the vestibular ganglion cells: heavily myelinated, lightly myelinated, and unmyelinated, respectively. In the perinuclear region of the vestibular ganglion cell, well developed and aggregated cytoplasmic organelles such as endoplasmic reticulum, mitochondria, and Golgi apparati were observed. In the perinuclear region of the Schwann cell relatively large mitochondria were characteristically observed. In the fractured view of the vestibular nerves, most of vestibular fibers were compactly myelinated. In the vestibular nucleus, the gathering of the neuronal cells were observed with the NaOH maceration method. PMID- 8470485 TI - Development of the chick vestibular ganglion and its nerve terminating in the endorgan. AB - We investigated the morphological maturation of the vestibular ganglion and its dendrites terminating in the sacculus of the chick embryo. The cytoplasm of the ganglion cells had acquired a granular feature due to the abundance of ribosomal clusters and rER by the 13th day of incubation. The myelination of the dendrites occurred before that of the perikarya. Compact myelin of the dendrites was observed on the 13th day of incubation, while that of the perikarya was observed in the 20th day of incubation. Nerve endings of afferent and efferent character were observed first in the sacculus on the 13th day of incubation. Positive immunoreactvity of substance P was observed on the 13th day of incubation. It is suggested that the morphological basis of functional activity is present on or around the 13th day of incubation. PMID- 8470486 TI - Some neurosurgical and clinical neurophysiological notes on selected neurootological problems. With special reference to acoustic neurinoma, brain death, and NVC. PMID- 8470487 TI - Progress of caloric response of vestibular neuronitis. AB - Progress of caloric response and subjective symptoms of 60 patients with vestibular neuronitis was evaluated by a long term follow-up study. Normalization of caloric responses was confirmed in 25 (41.7%) out of 60 patients, 20 of whom had recovered within 2 years of the onset of vertigo. The rate of the patients with canal paresis was about 90% after 1 month of the onset, and 80% after 6 months, while 50% of them still showed canal paresis after 5 or 10 years had passed. Complete relief from subjective symptoms was recognized in 34 (56.7%) cases during the follow-up period. We conclude that the prognosis of vestibular neuronitis is not always good, because vestibular function did not recover within normal levels in about half of the patients in spite of complete relief from subjective symptoms in many of them. PMID- 8470488 TI - Importance of cervical muscles in galvanic body sway test. AB - Retro-auricular galvanic stimulation in Romberg's posture elicits body sway which consists of an initial response (IR) and a deviation response (DR). Generally, anodal stimulation of the right side elicits IR to the left and DR to the right. We measured the deviation response (VDR) in various conditions in normal subjects. There was no significant difference between mean VDR in the standing posture weighted on the left foot (0.49 +/- 0.17 cm) and on the right foot (0.39 +/- 0.20 cm). Stimulation in the squatting posture also elicited IR to the left and DR to the right. Stimulation of the right side produced DR backward and to the right in the condition of the head facing to the right, and forward and to the right in the condition of the head facing to the left. The same body sway response as the after galvanic stimulation was also induced by non-galvanic maneuvers like inclining the head or moving the finger. Anodal stimulation in the sitting posture elicited slight but apparent head inclination to the stimulated side. These results suggest that cervical muscles play an important role in the galvanic body sway test (GBST), viz. IR and DR seemed to be secondarily produced by changes in the muscular tension of the neck. PMID- 8470489 TI - Vestibular neuronitis evaluated by the combined galvanic test. AB - Forty-two patients with unilateral vestibular neuronitis were examined by the combined galvanic test (CGT), consisting of the galvanic eye movement test (GEMT) and the galvanic body sway test (GBST). Results of the CGT were evaluated with respect to the time period from the onset of vestibular neuronitis. A favorable recovery was observed earlier with the GBST than the GEMT. We believe that this discrepancy may be due to the difference in compensation between the vestibulo ocular reflex and the vestibulo-spinal reflex. PMID- 8470490 TI - Interpretation of the combined galvanic test. Findings from cases with vestibular neuronitis. AB - The combined galvanic test (CGT) was developed in our department for simultaneous recording of galvanic eye movement test (GEMT) and galvanic body sway test (GBST). Twelve cases of vestibular neuronitis were studied first with the caloric test, and then with the CGT. The findings of the caloric test corresponded to those of the GEMT, but did not always correspond to those of the GBST. Thus we suggest that the GBST reflects an abnormality in a system different from that reflected by the caloric test and GEMT. It is likely that the caloric response mainly originates from the semicircular canal system. Thus the GEMT may reflect an abnormality in the semicircular canal system, while the GBST reflects an abnormality in the otolithic system. The CGT may thus be a feasible method of differentiating the disorders of the semicircular canal system from those of the otolithic system in the vestibular nervous system. PMID- 8470491 TI - Relationship between GBST and equilibrium examination in vestibular neuronitis. AB - Eleven patients with vestibular neuronitis were followed up from 1988 to 1990. The relationship between the GBST and other vestibular examinations was investigated. Vertiginous symptoms showed relative improvement, but in the last medical examination 4 out of 11 cases (36.4%) complained of unsteadiness when their head was rotated and fatigued. Seven patients (63.6%) presented spontaneous and positional nystagmus at the first consultation, but only one patient (9.1%) at the last one. Seven patients (63.6%) showed canal paresis to caloric stimulation, while 3 (27.3%) showed normal responses. In the galvanic body sway test (GBST), 9 patients (81.8%) showed abnormal thresholds. There was no significant relationship between vertiginous symptoms in the last medical examination and prodromes, vertigo type, nystagmus, righting reflex, caloric stimulation or the results of the GBST. PMID- 8470492 TI - Retro-labyrinthine disorder in cases with peripheral facial palsy. AB - In some previously reported cases, facial palsy, even in Bell's palsy, involved vestibular dysfunction. Vestibular dysfunction in facial palsy is considered to be due to a retro-labyrinthine disorder such as vestibular neuronitis or acoustic neuromas. For the past 9 years we have been using the galvanic body sway test (GBST) routinely for differential diagnosis of the vestibular system. This paper reports GBST detected, retro-labyrinthine disorders in facial palsy. From 1981 to 1989, equilibrium examinations were performed in 33 cases with Bell's palsy and in 12 cases with Hunt's syndrome within 2 weeks after the onset. GBST was tested in 10 out of the 17 cases showing canal paresis (CP) in the caloric test. Abnormal GBST responses were detected in 9 cases (90%), 4 (80%) with Bell's palsy and 5 (100%) with Hunt's syndrome. The incidence of abnormal GBST was very high not only in Hunt's syndrome but also in Bell's palsy. The results indicate that vestibular dysfunction combined with facial palsy is mainly due to a retro labyrinthine disorder and suggest that what is called vestibular neuronitis might be caused by a pathogenesis similar to that of facial palsy. PMID- 8470493 TI - Clinical significance of the galvanic body sway test in cerebellopontine angle tumors. AB - Since 1984, we have been modifying a new method of recording fine body sway elicited by low current stimuli of less than 0.4 mA, and of quantitatively evaluating the responses by Fourier transform. In order to easily and early detect acoustic tumors, we have applied a test battery consisting ABR, caloric test and galvanic body sway test (GBST) to 31 cases with acoustic neurinoma, to 5 cases with other CPA-tumors, and to 24 cases suspected of having CPA tumors. Of 27 cases with acoustic neurinoma on whom the GBST was performed, 25 cases (92.6%) shows abnormal responses. On the other hand, the ABR was abnormal in all cases, except for one case in the early stage of an ear tumor. However, the ABR was positive in 12 cases out of 24 with suspected findings without tumor, but the GBST was positive in only 3 cases out of 17 tested. Moreover, 26 cases (83.9%) with acoustic tumors showed abnormal CP in their first caloric tests. Comparing these observations with the results of image diagnosis, we conclude that the GBST is as useful for detecting small acoustic neurinomas as the ABR and the carloric test. Therefore, we have routinely used a test battery consisting ABR, caloric test and GBST for evaluation of acoustic neurinomas. However, we could not differentiate between acoustic neurinoma and CPA-tumor by using the three-test battery. PMID- 8470494 TI - Vestibular compensation in vestibular neuronitis: evaluation of positional nystagmus and caloric nystagmus. AB - We evaluated the vestibular functions, especially for positional nystagmus and caloric nystagmus, in 43 cases of vestibular neuronitis for long periods after its onset. It is shown that in the cases of vestibular neuronitis that were studied more than 10 years after the onset of the disease, the completed vestibular compensation changed or the vestibular compensation was still incomplete. PMID- 8470495 TI - Vestibular neuritis: an overview using a classical case. AB - Although acute unilateral and/or bilateral vestibular paralysis, known as vestibular neuronitis, is the second most common cause of vertigo (the most common is benign paroxysmal positional vertigo (BPPV), it is fraught with controversies. The clinical symptoms and methods of treatment of vestibular neuronitis are well defined; however, the etiology and pathophysiology of this disorder are still sketchy. Furthermore, there are no specific diagnostic tests available, and unfortunately, there are no animal models for this disorder. The purpose of this paper is to present an overview of those controversies using a classical case of vestibular neuronitis. PMID- 8470496 TI - Recovery of the vestibular function after vestibular neuronitis. AB - We performed steroid therapy on 34 cases with vestibular neuronitis and compared them with 77 patients not subjected to this therapy to examine the role of recovery of their vestibular function. Since no relation was noted between use of steroid and changes in subjective symptom of dizziness, the use of steroid is likely to facilitate the disappearance of spontaneous nystagmus in the early recovery stage. Canal paralysis recovered significantly by steroid and in cases of slight and moderate paralysis at the onset, recovery was more significant. Steroid therapy is argued to be effective for the recovery of vestibular function in cases of vestibular neuronitis. PMID- 8470497 TI - Follow-up of square drawing test in vestibular neuronitis. AB - The square drawing test (SDT) devised by Sekitani (1975), which is a modification of Fukuda's vertical writing test, was performed to evaluate vestibular dysfunction in 15 patients with vestibular neuronitis followed up for a long period. In particular, two parameters (distance and total length) were analyzed in the present study. Distance was analyzed by dividing the 15 cases into 3 groups. The largest group showed a tendency to shorten at an early stage. Total length was examined by dividing the 15 cases into 3 groups. The largest group showed a tendency towards macrographism at an early stage. It was found that as the degree of caloric responses recovered, the range of distance and total length decreased. Considering the correlation between parameters of the SDT (distance and total length) and caloric responses we concluded that the SDT is a feasible method to evaluate and follow up patients with vestibular dysfunction. PMID- 8470498 TI - Prolonged dysequilibrium in three cases with vestibular neuronitis: efficacy of vestibular rehabilitation. AB - The clinical course of acute unilateral vestibular disturbance in 3 cases with vestibular neuronitis and a case with labyrinthine destruction was surveyed for a long-term period. Vestibular training with a modified Cawthorne-Cooksey's exercise was done in 2 of 3 cases with vestibular neuronitis and a case of labyrinthine destruction. All had no severe troubles in activities of their daily lives over one year after the onset of the disease, but the central compensation was not completed, even in a young patient, in a case of labyrinthine destruction and in a well trained case. Spontaneous nystagmus to the affected side and increase of body sway with eyes closed were revealed by examinations in all cases. Physical exercise was found to be effective for relief from vestibular ataxia, but it was difficult to keep the effect even after training. PMID- 8470499 TI - Dynamic properties of feed back control of human posture in subjects with vestibular neuritis. AB - Postural control was studied in 22 subjects with vestibular neruitis within 14 days after the onset of symptoms. Dynamic feed back control of posture were evaluated by analyzing the postural responses to vibration toward calf muscles applied according to a PRBS schedule. Properties of the dynamic control was normalized as swiftness, stiffness and damping of the responses. There was no prominent group differences between the 22 subjects with vestibular neuritis and 17 normal subjects. However, when studying the change in parameters evoked by presence or absence of visual information it was found that the abundant changes of control parameters, especially in stiffness, met in normal subjects had declined in subjects with vestibular neuritis. The present finding suggests that although subjects after an acute vestibular lesion may achieve a sufficient postural control by utilizing information from other somatosensory receptors, this is concomitant with changes of the feed back control. PMID- 8470500 TI - Vestibular neuronitis in children. AB - Seventeen cases of vestibular neuronitis in children, including 11 cases from the questionnaires of an epidemiological survey in Japan and 6 patients in our clinic, were examined. Sex and age distribution was 11 males and 6 females, ranging in age from 3 to 15 years. Bilateral and recurrent cases were not encountered. Fifty-three percent of children had had a preceding episode of an upper respiratory tract infection and this ratio was higher than that in adults. The etiology of vestibular neuronitis is probably many-faceted, but it is thought that upper respiratory tract infections play an important role especially in children. Vertiginous symptoms had almost subsided among children at the last visit. However, among adults, 24% of patients felt persisting unsteadiness. The disappearance of positional and positioning nystagmus was observed in 71% of children at the last visit. Caloric CP failed to recover in only 14% of all cases who were re-examined. As shown in this study, the prognosis in children is better than in adults for nystagmus and caloric response. The results of this study thus indicate that not only central compensation but also recovery of the peripheral vestibular function is more effective for bringing recovery from the vestibular disorder in children than in adults. PMID- 8470501 TI - Vestibular neuronitis in aged patients: results from an epidemiological survey by questionnaire in Japan. AB - An epidemiological survey of vestibular neuronitis in Japan was done using a questionnaire. Answer sheets were obtained from 619 patients with vestibular neuronitis. In order to evaluate data from aged patients, 74 cases were singled out. The following results were obtained: i) There was no sexual difference and no laterality of affected side; ii) There was no case of bilateral vestibular neuronitis; iii) Ten cases were reported as recurrent. Aged patients had a relatively high rate of recurrence; iv) About 10% of 74 cases had had an upper respiratory tract infection, and this rate was lower than that for patients under 65 years of age; v) Thirty-five cases had complications. Hypertension was the most common complication; vi) The caloric test was re-used in 28 cases. The continued existence of caloric CP was observed in 23 cases upon re-examination. PMID- 8470502 TI - Bilateral vestibular neuronitis. AB - Bilateral vestibular neuronitis with a different onset time for each affected side was reported in two cases among 74 cases observed. The first case appeared 3 weeks and the other 5 years before involvement of the second ear. In the case with a short period before the second attack, the direction of nystagmus was unchanged throughout the clinical course. It is suggested that the direction of nystagmus depends upon the severity of each vestibular dysfunction. In the case with a long period when the vestibular compensation has been completed, paralytic nystagmus was observed and its direction corresponded with the side affected by canal. PMID- 8470503 TI - A clinical observation of benign paroxysmal positional vertigo (BPPV) after vestibular neuronitis (VN). AB - We observed 9 cases of BPPV developed after vestibular neuronitis. The interval between the onset of BPPV and vestibular neuronitis ranged from 2 weeks to 20 years. All cases were examined for critical head position which provoked vertigo, non-gaze nystagmus, positional and positioning nystagmus and caloric nystagmus. No characteristic signs and symptoms could be observed. The function of the posterior canal is thought to be necessary to provoke positional vertigo. Thus in BPPV after vestibular neuronitis the function of the posterior canal would presumably have been preserved to some degree. The first possibility is that the function of the posterior canal was not impaired in spite of the damage of the lateral canal. The fact that each canal differs in involvement in vestibular neuronitis may be explained by the difference in the blood supply or the innervation between lateral and posterior canals. If only the artery or nerve which is related to the lateral canal is damaged and the artery or nerve to the posterior canal is not involved, then the function of the posterior canal is preserved. So BPPV may occur soon after the disappearance of severe vertigo. The second possibility is that if the posterior canal had been damaged together with the lateral canal and the functions are recovering, BPPV may occur some time after the onset of vestibular neuronitis. The locus of vestibular neuronitis is in the peripheral vestibular system and the extent and degree of the lesion vary, which may explain why there can be time difference of the recovery between the two canals. PMID- 8470504 TI - Cerebellar infarctions and 'vestibular neuritis'. AB - Consecutive subjects 50 to 75 years of age with sudden onset of vertigo but without cochlear or neurological symptoms were investigated with neuro-imaging techniques. Doppler sonography of the vertebral and carotid arteries and recording of voluntary saccades and pursuit eye movements, caloric, spontaneous, gaze and optokinetic nystagmus. Among those studied, 6 out of 24 subjects could be demonstrated to have cerebellar infarctions, another 2 subjects had occlusion of one vertebral artery. Caloric tests could not identify subjects with a cerebellar infarction whereas prominently reduced pursuit eye movements could. Subjects with cerebellar infarction either had a vertebral artery occlusion or prominent cardio-embolic risk factors. It is suggested that subjects with symptoms as vestibular neuritis should be investigated with pursuit eye movements and with at least standard ECG recordings. PMID- 8470505 TI - Neuroborreliosis in the etiology of vestibular neuronitis. AB - Symptoms and incidence of neuroborreliosis (NB) were studied in ambulatory patients visiting the ENT clinic in Helsinki. Especially we tried to search for possible markers indicating the connection between vestibular neuronitis and NB. A total of 350 patients were screened with the enzyme-linked immunosorbent assay (ELISA) technique for possible antibodies against Borrelia burgdorferi (BB). Twelve patients had positive serological reactions for BB with sera titer levels ranging from 640-14700 (normal < 500). In 2 additional cases, NB was clinically confirmed. In 7 cases a history of tick bite and in 4 cases erythema chronicum migrans was confirmed. In 9 cases, vertigo was the predominant symptom, and in 3 cases the symptoms were linked to facial nerve paresis. Six patients suffered from hearing loss. In 7 cases, the diagnosis was initially settled as vestibular neuronitis. NB seems to be present in about 4% of cases with apparent otologic diseases in Finland. In the majority of the cases, the disease resembles vestibular neuronitis in the acute stage. Since NB is tractable, all patients visiting the ENT clinic, especially those with vertigo, should be screened. PMID- 8470506 TI - Viruses and vestibular neuritis: review of human and animal studies. AB - There is increasing evidence in man and animals that several human viruses can damage the vestibular labyrinth. Clinical and serologic studies of patients with vestibular neuritis suggest that the viruses may play a role in the pathogenesis of this disease. Temporal bone studies of patients dying after vestibular neuritis have found maximal damage in the distal branches of the vestibular nerve. These changes are felt to be consistent with a viral etiology. No satisfactory animal viral model of vestibular neuritis currently exists. However, animal studies have demonstrated that several human viruses including rubeola, herpes simplex, reovirus, mouse and guinea pig cytomegalovirus, and neurotropic strains of influenza A and mumps virus, can infect the vestibular nerve and the vestibular membranous labyrinth. PMID- 8470507 TI - Vestibular neuronitis: epidemiological survey by questionnaire in Japan. AB - An epidemiological survey on vestibular neuronitis in Japan was conducted by means of a questionnaire filled in by major neuro-otology clinics (otolaryngologists) during 1988-1990 (3 years). The diagnostic criteria of vestibular neuronitis settled on in 1986 by the Standardization Committee of the Japan Society of Equilibrium Research were applied. Gross analysis of questionnaire answers showed that i) there was no sexual difference, ii) the peak of age distribution was between 40-50 years, iii) about 30% of all cases had had common colds prior to the disease, the rate being highest among children below 10 years, iv) disappearance of positional and positioning nystagmus appeared in about 60% of all cases within 3 months, and that v) caloric CP was observed in about half of the cases at the follow-up test. Progress was not as favorable when compared to previous studies. PMID- 8470508 TI - Lyme disease with neurological complications in Japan. PMID- 8470509 TI - Histological changes of vestibular nerves and ganglion cells in the acoustic tumor in relation to clinical functions. PMID- 8470510 TI - Auditory and vestibular pathology in brainstem death revealed by auditory brainstem response. AB - Auditory brainstem response (ABR) before and after the cessation of brainstem activity and postmortem histological findings in the temporal bone and auditory and vestibular pathways of two cases of brainstem death are reported. A brainstem death state of at least 48 h in Case 1 and of at least 24 h for the left side and several hours for the right side in Case 2 was demonstrated by neurological examination, flat EEG, and persistent absence of ABR. Postmortem examination was performed 3 h after death in Case 1, and 1 h after death in Case 2. Pathological studies of the entire length of the auditory and vestibular pathway revealed total autolysis of the organ of Corti and vestibular endorgans and swollen cochlear and vestibular ganglia in Case 1, and, in Case 2, on the right side, preservation of the organ of Corti and vestibular endorgans and mildly swollen cochlear and vestibular ganglia, but on the left side, destruction of the organ of Corti and vestibular endorgan and markedly swollen cochlear and vestibular ganglia. We believe that distinct pathological changes in auditory and vestibular endorgans, and other changes of the cochlear and vestibular ganglia as observed in these two cases, may develop if the duration of absent ABR is prolonged. PMID- 8470511 TI - Recent advances in neurotology and otolaryngology. Papers dedicated to Professor Kanemasa Mizukoshi upon his retirement as Director of the Department of Otolaryngology, Toyama Medical and Pharmaceutical University, Faculty of Medicine. PMID- 8470512 TI - Body sway response to experimental unbalance in normal subjects and patients with unilateral vestibular disorders. AB - The function of maintaining posture during temporary unbalance caused by experimental vestibular asymmetry was studied. Galvanic stimulation to the vestibular nerve causing body deviation to the stimulated ear was given to 31 normal subjects and 16 patients with peripheral vestibular disorders. The velocity of spontaneous body sway and that during body deviation caused by the galvanic stimulation were compared. The spontaneous body sway velocity was significantly higher than that of normal subjects. In normal subjects, the body sway velocity during body deviation remarkably increased, while that in patients did not. It is considered that large body sway in patients might conceal the fine compensatory body sway during the body deviation and that patients with unilateral vestibular dysfunction who have large body sway are always in a dysfunction state similar to that which normal subjects experience during body deviation caused by galvanic stimulation. PMID- 8470513 TI - Vestibular nerve disorder in patients suffering from sudden deafness with vertigo and/or vestibular dysfunction. AB - Vestibular nerve disorder (VND) in cases suffering from sudden deafness with vertigo was studied. Between 1987 and 1991, we observed 46 patients suffering from sudden deafness with or without vertigo, who had undergone the caloric test and galvanic body sway test (GBST). Twenty-seven patients had vertigo and canal paresis (CP) upon the caloric test, 6 vertigo without CP and 13 CP without vertigo. VND was detected in 12 of the 46 patients. All those with VND had vertigo and CP upon the caloric test, 12/27 (44%). The degree of hearing loss in those with VND was significantly (p < 0.05) more severe and their recovery of hearing loss was poorer than in patients without VND. These results indicate that VND is a common finding in cases of sudden deafness with vertigo especially in those with severe hearing loss. PMID- 8470514 TI - The contribution of proprioception to posture control in normal subjects. AB - In order to investigate the contribution of proprioceptive input to maintaining an upright position, stabilometry via 100-Hz vibratory stimulation applied to the Achilles tendon was studied and analyzed with respect to area, length and power spectra according to the method of fast Fourier transform (FFT). Twenty-one young medical students were analyzed in this study. When vibration was applied, the body sway was significantly greater than that of control in area and length with both eyes open and closed. There was a significant increase of total power in both the lateral (X) and antero-posterior (Y) directions with the eyes closed. With the eyes open, an increase was found only in the antero-posterior direction. The frequency band indicating the maximum spectrum did not shift. Significant increases in power spectra were found in the frequency range of more than 2 Hz in both two directions with the eyes closed. It was concluded that a vibration given to the Achilles tendon provoked a pronounced high frequency body sway especially in the antero-posterior direction when visual information was nullified, and that proprioceptive information may have a minor role compared with visual information. PMID- 8470515 TI - Contribution of vision to the stabilization of body sway in patients with spinocerebellar degeneration. AB - Body sway was recorded with closed eyes, open eyes and visual feedback for 30 s each. Thirteen patients with spinocerebellar degeneration and 17 age-matched normal controls underwent the examination. Four parameters (area, length, sums of frequency spectrum in the anterior-posterior and lateral directions) were computed. Furthermore, Romberg ratios between closed and open eye conditions [Romberg c/o] and Romberg ratios between closed eyes and visual feedback conditions [Romberg c/f] were computed. Four parameters were significantly greater in the patients with spinocerebellar degeneration than in the normal controls. However, three of eight Romberg ratios were significantly greater in the patients with spinocerebellar degeneration than in the normal controls. The results implied that the proprioceptive-posture loop was mainly disordered while the visuo-postural loop was intact in patients with spinocerebellar degeneration. PMID- 8470516 TI - Evaluation of vestibular function by dynamic posturography and other equilibrium examinations. AB - We evaluated the significance of dynamic posturography (EquiTest) in vestibular function assessment by comparing it with our routine equilibrium examinations comprised of nystagmographic data and other postural tests. Fifty-two patients with unilateral peripheral vestibular disorders were examined. Differences in test results between pendular rotation test and dynamic posturography were found in 23 out of 52 (44%) patients with unilateral peripheral vestibular disorders. In 5 patients, no abnormality of vestibular function could be detected by means of a three-test battery (spontaneous and positional nystagmus and pendular rotation test) used for evaluating vestibular compensation. In spite of these results, the patients complained of vertigo of dizziness and showed abnormal results in dynamic posturography. Dynamic posturography was superior to other postural tests in the detection of pathology corresponding with the patients' complaints. From these results, dynamic posturography (EquiTest) appeared to provide new information about such conditions of vestibular patients which other equilibrium examinations have not heretofore been able to detect. PMID- 8470517 TI - A case of Bickerstaff's encephalitis. With special reference to neurotological findings. AB - The case of a 60-year old male with prodromal common cold symptoms and progression of brain stem involvement with no cardiac or respiratory complications is described. This conformed to the criteria of Bickerstaff's encephalitis. Neurotological examinations, including the OKN test, the caloric test, and the GBST were performed from onset to recovery of the disease. The results of these tests closely reflected the central nervous system disorders each time, but there was a discrepancy in the results of the two test batteries of equilibrium function, the caloric test and the GBST. The caloric test showed bilateral canal paresis while the GBST showed normal responses. These results suggested that the involved area of the vestibular nucleus was localized to the superior portions. Form our clinical observations, we can conclude that neurotological examinations provide more vital information for localized diagnosis and follow-up of the brain stem lesion in Bickerstaff's encephalitis. PMID- 8470518 TI - Complex spike responses of cerebellar Purkinje cells to constant velocity optokinetic stimuli in the cat flocculus. AB - In the cat cerebellar flocculus without cerebrum but with intact accessory optic tract, complex spike (CS) responses to horizontal optokinetic stimuli (velocity step at 2 degrees/s) were investigated. The directionally selective CS responses were present only during the short-duration stimuli but not during the continuous unidirectional stimuli. Following the end of the stimuli during the stationary surround phase, the CS activity was modulated in a manner opposite to the preceding CS response during the stimulation. These CS responses cannot simply be interpreted as sensory responses to the retinal slip input; they may in fact be deeply associated with the motor control command of the eye movement which would be elicited by the retinal slip. PMID- 8470519 TI - Autonomic nervous system disturbance as etiological background of vertigo and dizziness. AB - In order to investigate whether dysautonomia lies behind vertigo and/or dizziness in the neurotological clinic, an electrocardiogram (ECG) R-peak to R-peak test (R R test) along with the Schellong test were simultaneously performed in 136 subjects. ECG data were analyzed by a microcomputer, and R-R intervals were calculated. In a dynamic test performed during postural changes from the supine to the standing position, there were 23 of 55 (41.8%) positive test results in patients with peripheral vestibular disorders, 28 of 51 (54.9%) with central vestibular disorders, and 15 of 18 (83.3%) with spinocerebellar degeneration. In a static test with the patient in the standing position, there were 13 of 55 (29.1%) positive test results in patients with peripheral vestibular disorders, 16 of 51 with central vestibular disorders, and 8 of 18 (44.4%) with spinocerebellar degeneration. A significant difference in the positive rate between spinocerebellar degeneration and both other central and peripheral vestibular disorders in the dynamic test was observed. These results also demonstrated that dysautonomia upon postural changes might play an important role in the development of vertigo and dizziness and that it is provoked by disorders of the autoregulatory mechanisms of the cerebral blood flow. This test is presumed to be excellent for detecting dysautonomia by virtue of being non invasive, having good reproducibility and being readily available to quantitative evaluation by using a microcomputer. PMID- 8470520 TI - Result of decompression surgery in late-stage severe facial paralysis. AB - We investigated the usefulness of decompression surgery in the treatment of the facial nerve in 23 patients with severe complete facial paralysis regardless of etiology. All patients were followed up for at least one year after onset. Nine patients underwent decompression surgery within a month of onset (Group A), 10 underwent surgery at a later time (Group B), and 4 did not receive surgery (Group C). In Group A, 2 patients showed satisfactory recovery and 2 fair recovery. In Group B, 4 patients showed satisfactory outcome, and one patient who underwent surgery 131 days after onset showed fair outcome. No patient in Group C showed satisfactory or fair recovery. There were no significant differences among the three groups in the percentage showing sequelae after treatment. We conclude that decompression surgery is indicated even for patients with severe facial paralysis who have a history of palsy of 2 months' or more duration. PMID- 8470521 TI - The fine structure of the guinea pig tympanic membrane with special reference to the fiber arrangement. AB - The tympanic membrane of the guinea pig was studied by electron microscopy. The pars tensa was composed of three layers, i.e., the outer epidermis, the middle lamina propria and the inner mucosal membrane. The pars flaccida was negligible in size. The fibers in the lamina propria of the tympanic membrane were not clearly observable by conventional electron microscopy. With the silver methenamine method the fibers were more intensely stained than the epithelial cells and could thus be distinctly demonstrated by this method. In the inferior larger portion of the pars tensa, the lamina propria contained the outer radial and the inner circular fiber bundles. The radial fiber bundles were thicker and more densely packed than the circular ones. This fact indicates that the radial fibers form the major skeleton of this portion. The superior smaller portion of the pars tensa contained several layers of irregularly arranged fiber bundles in the lamina propria and was considerably thicker than the inferior larger portion. PMID- 8470522 TI - Middle ear barotrauma associated with hyperbaric oxygenation treatment. AB - We investigated the signs and symptoms of middle ear barotrauma in 67 patients with hyperbaric oxygenation treatment as well as the influence of predisposing factors. Ear damage was classified into 5 grades on the basis of objective findings at otoscopic examination. The incidence of middle ear barotrauma assessed by objective criteria was 68.7%, and showed little variation with age or primary disease. On the other hand, the incidence assessed by subjective symptoms was lower than the objectively-based incidence in aged patients, those with severe neurological diseases, and those who had difficulties speaking. Patients with a trauma grade of 2 or more complained of severe symptoms and were appropriate candidates for treatment. It is considered that otoscopic examination should be performed in patients who undergo hyperbaric oxygenation treatment and that prior management of nasal and paranasal diseases is beneficial in the prevention and treatment of middle ear barotrauma. PMID- 8470523 TI - Immunologic study of the hyaline-vascular type of Castleman's disease. A case study. AB - We report a case of Castleman's disease in a 48-year-old male who complained of a rapidly enlarging mass on the neck. Thrombocytopenia and the facio-scapulo humeral type of progressive muscular dystrophy were also present. The mass was extirpated, and histopathological examinations showed the hyaline-vascular type of Castleman's disease. Following resection, thrombocytopenia was ameliorated. Immunological study with flow cytometric analysis was made to clarify the nature of his mass. With reference to recent literature we suggest that the hyaline vascular type of Castleman's disease may be an atypical hyperplasia of the lymphoid tissue. PMID- 8470524 TI - Nasal septal neurinoma. AB - A case of nasal septal neurinoma is presented. The patient was a 71-year-old male who complained of nasal obstruction and epistaxis. Results of the physical examination showed a giant mass filling the nasal cavity and the nasopharynx. A biopsy taken from its tissue surface showed histological features of neurofibroma. The lesion was completely resected with the patient under general anesthesia. The tumor completely occupied the right nasal cavity and the nasopharynx, partially penetrated the nasal septum and extended to the left nasal cavity. After the operation, the final pathological diagnosis was not neurofibroma but neurinoma in which Antoni type A and type B cells were mixed. The postoperative course was uneventful, and no recurrence has been observed to date. PMID- 8470525 TI - Botulinum toxin treatment for spasmodic dysphonia. AB - Effective treatment of adductor type spasmodic dysphonia with botulinum toxin injection is presented. Patients showed objective and/or subjective improvement in phonation. The beneficial effect lasted for approximately 3 months. An immediate complication is temporary hoarseness or aphonia, mainly due to diffusion of BT into the adjacent muscles. This is avoided by limiting the injection to one vocal fold only and by keeping the dose at less than 5 units. Insertion technique of the needles, such as percutaneous and laryngoscopically controlled techniques, are discussed. PMID- 8470526 TI - Direction selective climbing fiber responses to horizontal and vertical optokinetic stimuli in the cat cerebellar flocculus. AB - In ketamine anesthetized cats, complex spike (CS) responses to movement of a large-field visual surround (optokinetic stimulus) were recorded in the cerebellar flocculus. Two types of Purkinje cells were found. One type showed increased CS activity to optokinetic stimuli directed contralaterally to the recording site and decreased activity to stimuli directed ipsilaterally. The modulation occurred in both monocular (responses to the stimuli for only the ipsilateral eye) and binocular forms (dominant eye, ipsilateral). The other type of cell showed increased CS activity during upward optokinetic stimuli and decreased activity during downward stimuli. The responses occurred only in the binocular form. The dominant eye was either ipsilateral or contralateral with respect to the recording site. Thus, there are two types of Purkinje cells in the cat flocculus: horizontal type cell showing CS modulation during horizontal optokinetic stimuli, and vertical type cell showing CS modulation during vertical optokinetic stimuli. PMID- 8470527 TI - Quantitative evaluation of the function of looking at visual target in optokinetic nystagmus. AB - A new method is presented to qualitatively evaluate the function of OKN which certainly looks at a visual target. Optokinetic stimulation was given to a test subject by projecting stripes with a 5 degrees visual angle width at 30 degrees intervals, which was accelerated by 1 degree/s2 up to 100 degrees/s. The correlation between slow phase and fast phase was computed with our program. Two correlations were mixed in a normal response, one indicated low correlation and the other high correlation. As normal subjects look at wide interval visual targets one by one regardless of the target velocity, low correlation type OKN beats are considered to be those which certainly look at the visual target. In order to quantitatively analyze this type of OKN, approximate regression lines of the low correlation type, [y = ax + b (x: slow phase velocity, y: fast phase amplitude or velocity)], were computed by the minimum square method. In normal subjects, value a indicates low and value b high velocity and their normal limits are determined. The results of cases with central disequilibrium indicate that this analysis provides information of pathological OKN different from that of such conventional parameters as slow phase velocity and number of nystagmus beats. PMID- 8470528 TI - Otoconia in young and elderly persons: a temporal bone study. AB - Using serially sectioned human temporal bones, the volumes of otoconia masses were compared between young children and elderly people. The latter group had significantly less otoconia volume than the former group, both in the macula utriculi and macula sacculi. The ratio between macula utriculi and macula sacculi was 100:70 in the young group, whereas it was 100:35 in the elderly group. Thus, the macula sacculi in the elderly group showed the severest otoconia reduction. PMID- 8470529 TI - The fine structure of the developing otolithic organs of the rat. AB - The fine structure of the otolithic organs in fetal and neonatal rats were studied by light and transmission electron microscopy. The otoconia were found at the 16.5 gestational day while the otolithic membrane appeared much later. Types II and I hair cells were first observed at the 16.5 and 18.5 gestational days, respectively. Secretory granules in the supporting cells seemed to release an organic material which was destined to be incorporated into the organic matrix of the otoconia and/or the otolithic membrane. Protrusions of apical cytoplasm, cytoplasmic globules and dilated rough endoplasmic reticulum (rER) were observed in epithelial cells of both sensory and non-sensory regions, in particular, in the transitional cells. By contrast, otoconia were mainly located above the neuroepithelial area. The functional roles of protrusions and cytoplasmic globules in the genesis of otoconia remain to be clarified. In addition, the pathway for transport of calcium remains obscure. PMID- 8470530 TI - Salivary total protein and experimental Coriolis sickness. AB - Symptomatic reporting has been used in quantifying the severity of motion sickness including Coriolis sickness. This study was designed to objectively examine if the dynamic changes of salivary protein concentration relate to the severity of Coriolis sickness. Healthy adults with normal vestibular function underwent a modified Coriolis Sickness Susceptibility Index (CSSI) test, utilizing a staircase profile. Salivary samples were obtained prior to stimulation, 15, 30, and 45 min following stimulus onset, and/or upon reaching "nausea-II" endpoint. Total protein concentration tended to rise over the initial 30 min of stimulation, and then level off or decline. A statistically significant difference was found between the pre-stimulation and 30 min samples. Although some variability existed among the subjects, the general pattern of changes along the time course was similar. An inverse correlation approaching statistical significance was found between control (non-stimulus) total protein levels, and minutes of Coriolis stimulation required to reach the "nausea-II" endpoint. Thus, baseline salivary total protein levels can be of use in predicting susceptibility of Coriolis sickness and other forms of motion sickness. PMID- 8470531 TI - Effect of transdermally administered scopolamine on the vestibular system in humans. AB - In order to elucidate the effect of scopolamine on the vestibular system in humans, various experimentally-induced forms of nystagmus, i.e. caloric nystagmus, rotational nystagmus, optokinetic nystagmus, visual-vestibular interaction and optokinetic after nystagmus, were evaluated before and after the administration of two pieces of Scopoderm-TTS or placebo patches retro auricularly. Scopolamine reduced the responses of both the caloric and optokinetic after nystagmus compared with the placebo. The possible action site of this drug is discussed. PMID- 8470532 TI - Development of the vestibular aqueduct in Meniere's disease. AB - The external aperture width of the vestibular aqueduct was measured in living subjects of various ages, with normal and diseased ears. Measurements were made from 3-dimensional reconstruction of CT images, and the developmental process was studied. The following results were obtained. i) In Meniere's disease the external aperture was hypoplastic and its width significantly smaller than that in normal individuals and those with chronic otitis media, including children. ii) There were no significant differences between normal ears and ears with chronic otitis media in either adults or children. The development of external aperture was completed in childhood. iii) In Meniere's disease, hypoplasia evidently begins before childhood, which suggests that congenital factors are involved in the pathology of this disease. PMID- 8470533 TI - The intravenously administered glycerol test. AB - Three different methods of performing the glycerol dehydration test were evaluated. Method one involved the oral administration of 50 g of 50% glycerol solution; method two was the intravenous administration of 500 ml of 10% glycerol in saline with 5% fructose; and method three involved the administration of 200 ml of the same solution. It was found that intravenous administration was safe and did not give any unpleasant side effects. Both intravenously administered methods appeared to give similar rates of positive diagnosis for Meniere's disease. PMID- 8470534 TI - Furosemide VOR test for the detection of endolymphatic hydrops. AB - In order to detect endolymphatic hydrops, we applied three neuro-otologic examination methods, including the furosemide VOR test, the glycerol dehydration test, and electrocochleography in 61 patients with unilateral Meniere's disease, 21 patients with delayed endolymphatic hydrops, and 10 patients with syphilitic labyrinthitis. The positive rate of the furosemide VOR test in patients with endolymphatic hydrops was more than 50%. Inconsistencies were observed between the results of the furosemide VOR test, the glycerol test and/or electrocochleography. Therefore, combined test battery of these tests is useful clinically for detecting endolymphatic hydrops in the vestibular and cochlear systems. PMID- 8470535 TI - Intraoperative electrocochleography of endolymphatic hydrops surgery using clicks and tone bursts. AB - Seventy-seven ears of patients with Meniere's disease (n = 69) and other ears with secondary endolymphatic hydrops (n = 8) underwent valved shunt surgery, and were monitored with intraoperative electrocochleography (ECoG) using clicks stimuli (n = 77), and both clicks and tone bursts (n = 37). Of the 41 ears in which the "baseline" measurement was > 35% summating potential to action potential (SP/AP) amplitude click ratio, 23 ears (56%) showed a significant ratio decrease (improvement). Twenty-six ears out of the 37 that were monitored by both clicks and tone bursts had abnormal absolute SP tone bursts amplitudes at "baseline" and 8 ears (31%) changed to normal at "closing". When tone burst ECoG information is combined with click stimuli, our basic understanding of click ECoG is enhanced and our ability to assess electrophysiologic changes intraoperatively is improved. PMID- 8470536 TI - Electrocochleography in syphilitic hearing loss. AB - Syphilitic labyrinthitis presents such symptoms as hearing loss, tinnitus, vertigo and/or dizziness, and is well known as one of the endolymphatic hydropic diseases. In order to elucidate the relationship between syphilitic hydrops and ECochG findings, we performed ECochG in patients with syphilis following our previously reported study of patients with Meniere's disease. Twenty-two patients who have been serologically and clinically diagnosed as having syphilitic labyrinthitis were examined with ECochG between December, 1982 and November, 1991. Of the 27 ears tested with ECochG, 2 showed no response due to severe hearing loss, and increased SP (SP/AP ratio > 0.37) was observed in 14 (56.0%) out of the remaining 25 ears. The SP/AP ratio of patients with syphilitic labyrinthitis was not significantly different from that of the patients with Meniere's disease or delayed endolymphatic hydrops, while it was significantly higher than that of the patients with sudden deafness and other types of sensorineural hearing loss. We conclude that the electrocochleographic features of endolymphatic syphilitic lesions resemble those in Meniere's disease. PMID- 8470537 TI - Role of the dorsolateral pontine nucleus in two components of optokinetic nystagmus (OKN). AB - The anatomical features of the dorsolateral pontine nucleus (DLPN) implicate a role of the nucleus in the generation of smooth-pursuit eye movements. The DLPN receives convergent inputs from a variety of parieto-occipital cortical visual areas and projects its fibers to the flocculus and vermal lobules VI and VII. In addition to cortical afferent fibers, the DLPN receives descending fibers from the nucleus of the optic tract which is indicated as the first subcortical optokinetic nystagmus (OKN) relay. DLPN units respond not only to a discrete visual spot but also to large-field OKN stimuli. On the basis of the above anatomical and physiological features, OKN was investigated in 2 alert monkeys whose DLPN was physiologically identified and into which reversible lidocaine was injected. The present findings showed that a rapid rise in OKN velocity was reduced in both monkeys, whose lesions included the uppermost rostral part of the nucleus in the one monkey and the entire nucleus in the other, whereas optokinetic after-nystagmus velocity was affected only in the latter. Taken together with physiological data, the DLPN possibly shares the domain of low selectivity speed selection in OKN and does not play a main role in the generation of OKN. PMID- 8470538 TI - Delayed endolymphatic hydrops following acoustic tumor removal with intraoperative and postoperative auditory brainstem response improvements. AB - A 36-year-old female with delayed endolymphatic hydrops (ELH) after acoustic tumor removal of the same ear is reported. She presented at our clinic with pressure, fullness, and tinnitus involving her right ear. She had an abnormal auditory brainstem response (ABR), and a computed tomography showed a right acoustic tumor. She underwent a complete tumor removal from a suboccipital incision with significant intraoperative and postoperative ABR improvements. Preoperatively, there was no fluctuation in her hearing and her electrocochleography (ECoG) was normal. She did well postoperatively, but 18 months after the tumor surgery she complained of noticeable fluctuating hearing loss with increased tinnitus and aural fullness of her right operated ear and nausea but no vertigo. Neurotological examinations showed a positive right urea dehydration and positive right ECoG for enhanced summating potential to clicks. She was diagnosed as cochlear Meniere's disease with delayed ELH, failed medical management and then underwent a valved shunt surgery for ELH to stabilize her hearing. Eight years after her acoustic tumor surgery and 6 and a half years after her ELH surgery she has stabilized hearing with normal ABR and ECoG. Her clinical course is presented and a pathogenesis of ELH is discussed. PMID- 8470539 TI - Effects of isosorbide in patients with Meniere's disease. AB - The effects of isosorbide on vertigo, disability, hearing loss and tinnitus in 32 patients with Meniere's disease were evaluated after a 24-month observation period. Vestibular symptoms in 80% of patients were assessed as improved according to the 1985 AAO-HNS post-treatment reporting criteria. In contrast, the effect of this osmotic diuretic on cochlear symptoms was limited. PMID- 8470540 TI - An application of phase spectral analysis to amplitude-modulation following response. AB - A phase spectral analysis developed by Fridman (1982) was applied to the detection of amplitude-modulated frequency following response (AMFR) and its clinical usefulness was evaluated. A 1000 Hz sinusoidally amplitude-modulated tone with a modulation frequency of 40 Hz and a modulation depth of 90% was delivered to the right ear of 10 normal-hearing subjects. According to Fridman's technique, an ensemble of sweeps was divided into 10 groups and group averages were obtained. Then phase variances were calculated using fast Fourier transform for the group averages. In order to determine the optimal conditions of analysis for constructing an automatic detection program using phase spectral analysis, frequency spacing, number of sampling points and number of sweeps averaged per group were investigated. The sensitivity of phase spectral analysis for automatic detection of AMFR was also evaluated. The results suggested that the optimal number of sampling points and frequency spacing are 512 points and 4.9 Hz (observation window 204.8 ms), respectively. Concerning the average number of sweeps, the synchrony measure of the frequency component corresponding to the modulation frequency increased as the number of sweeps increased. Furthermore, it was demonstrated that threshold determination by phase spectral analysis is more sensitive than detection of the threshold by visual analysis of waveform configuration. PMID- 8470541 TI - Changes in auditory evoked responses during intravenous lidocaine. AB - Auditory evoked responses in 21 cases with tinnitus were recorded before and after the administration of intravenous lidocaine. A dosage of 1 mg/kg body weight was diluted with 20% glucose (20 ml) and administered intravenously over a one-min period. The loudness of tinnitus was evaluated during electrocochleography (ECochG) or auditory brain-stem response (ABR) recordings using a score between 0 and 11. The stimulus sound was a tone burst in a frequency that corresponded to the pitch of tinnitus. AP latency on ECochG and the inter peak latency (IPL) of wave I-III and wave III-V on ABR were prolonged momentarily and tinnitus was reduced. These findings reveal that the sites of action for lidocaine are both the inner ear and the brain-stem. PMID- 8470542 TI - Neurotological findings in patients with acute mumps deafness. AB - We report the neurotological findings in 4 cases of acute stage hearing loss due to mumps. In 2 of the cases, the less severe hearing loss which occurred in the opposite ear was shown to have improved after therapy. If patients with mumps suffer from a mild hearing loss which recovers quickly, the temporary auditory problem might go undiagnosed; thus the incidence of mumps deafness might well be higher than that reported in the literature. Two of our patients complained of dizziness. In the caloric test, a reduced response of the ear with poorer hearing was found in 3 cases, and a normal caloric response was revealed in the fourth. In the galvanic body sway test (GBST), 3 cases showed a normal response bilaterally and one case presented a normal response bilaterally in the first test, no response in the right side in the second test, and recovery of response in the third test. These findings suggest that an inner ear disorder might occur in combination with a retrolabyrinthine disorder in mumps deafness, with the former lasting longer and the latter improving earlier. PMID- 8470543 TI - Clinical usefulness of the personal computer for equilibrium examinations. AB - A personal computer (PC) system and its usefulness for equilibrium examinations is reported. The system was introduced into clinical routine practice for the following purposes: i) Reduction of test result measurement troubles in clinical practice, ii) Clearer observation of eye movements and body sway, iii) Quantitative analysis of nystagmus responses or body sway, iv) Easy introduction into clinical practice of new parameters or new tests, v) Programmable arrangement of stimulating devices, and vi) Effective storage of test data. Our PC system has been successful for these purposes and provided many useful options in equilibrium examinations. Although computer systems for equilibrium examination have not been popular due to high costs, the PC system, which can be obtained at a reasonable price, has become as powerful a device as the conventional small computer, and is expected to become a popular method for both research and routine clinical practice in the near future. PMID- 8470544 TI - Effect of intraoperative manipulation and preservation on fascia temporalis used in tympanoplasty. AB - Fascia temporalis (FT) is generally used as grafting material for primary or revision surgery for chronic ear disease. In the latter case, homologous FT, stored in various solutions after the intraoperative preparation, that aims to dehydrate, is often used. In this study, an ultrastructural analysis of FT has been carried out in order to determine whether its structure is affected by the different steps that take place before its application as a homograft. As well as light, transmission and scanning electron microscopy, immunoperoxidase technique for testing monoclonal antibodies against different collagen types was performed. The surface appearance of FT proved to be increasingly affected by the intraoperative manoeuvres. Moreover, 10% formalin proved to give a better preservation of the surface appearance of FT than did 70% alcohol which, also after a short period of preservation (15 days), caused severe surface alterations. No particular changes in the ultrastructural appearance of FT were noticed that could have been attributed to the length of preservation. Type IV collagen was detected in the 30-day samples of both alcohol- and formalin preserved specimens. From these results, one can speculate that, despite the major ultrastructural changes induced in FT by the intraoperative preparation and by its preservation, this tissue is still able to maintain a proper connective network. This finding could explain the reliability of homologous FT for the repair of tympanic membrane perforations. PMID- 8470545 TI - [High-frequency hearing thresholds prior to and following middle ear surgery]. AB - Middle ear surgery may affect the cochlea. On 80 patients, the mean HF thresholds before and after middle ear surgery including stapediotomy, combined approach tympanoplasty and myringoplasty are compared. A small deterioration of the mean HF thresholds up to 10 dB is observed. PMID- 8470546 TI - Fluctuating hearing loss in sarcoidosis. AB - Sarcoidosis is a systemic granulomatous disease, which can affect the vestibulo acoustic system at any level, causing vertigo and/or hearing loss. The main mechanism could be vasculitis. One patient with fluctuating hearing loss as the first manifestation of a systemic sarcoidosis is presented. Diagnostic modalities, especially different sites of biopsy or needle aspiration are discussed. The treatment is steroid therapy. Hearing will be restored provided no irreversible changes of the VIIIth nerve and/or the inner ear have occurred. PMID- 8470547 TI - The effects of ventilation tube placement on hearing, speech, language, cognition and behaviour. AB - As a part of a larger, multidimensional study on secretory otitis media (SOM) and its relation to children's development, the effects of ventilation tube (VT) placement on hearing, speech, language, cognition and behaviour were studied over a six month period. Children with a clear and persistent picture of SOM were examined just before tubes were inserted and again, with the same measures, six months later. Their evolution was compared to that of a control group. The results indicate, as was expected, that the hearing of the children with SOM normalized very quickly after surgery. Speech and expressive language functions were comparable for both groups at the two moments of examination. Only verbal comprehension of the SOM-group was found to be slightly improved in the course of a six month period. No differences in general cognitive functioning and in behaviour were found between both groups. PMID- 8470548 TI - Intracranial complications of cholesteatoma. AB - The incidence of cholesteatoma and its intracranial complications in 1450 patients treated for chronic middle ear disease at the ENT Department of the General Hospital in Osijek over a 15-year period is reported. Nearly 7.5% of patients suffering from chronic middle ear disease with cholesteatoma developed intracranial complications. The most frequent complication was meningitis. The mean age of patients with intracranial complications was 34.6 years. The average duration of the disease was 11.9 years. The surgical technique depends on the type of complication as well as the general condition of the patient. Brain abscess is treated through radical excision of the abscess and in poor risk patients, trepanation with aspiration is preferred. PMID- 8470549 TI - [Auricular leiomyoma]. AB - An auricular leiomyoma is reported. This neoplasm is extremely rare in the head and neck region. The clinical and histopathological features are discussed. PMID- 8470550 TI - Hibernoma of the larynx. Review of the literature and a new case. AB - Hibernoma is a rare, benign, soft-tissue tumour composed of cells similar to those of brown adipose tissue. Only seven cases in the cervical area have been reported and none in the larynx. A case of hibernoma of the pre-epiglottic area is presented and the histological, histogenetical and clinical features are discussed. PMID- 8470551 TI - [A case of 3d pharyngeal pouch sinus]. AB - The study of the branchial remnants needs a perfect understanding of the embryology of the branchial apparatus. Endoscopic excision using the CO2 laser in a very rare case of third pouch sinus is reported for the first time. PMID- 8470552 TI - [Sleep apnea syndrome. Evaluation following uvulopalatopharyngoplasty]. AB - 20 cases of uvulopalatopharyngoplasty performed on patients suffering from sleep apnea syndrome have been studied with a pre- and post-operative polysomnographic recording. Eleven patients (55%) responded to this therapy and showed a significative decrease of their post-operative apnea-hypopnea index. An increase of the mean oxygen saturation was noticed during sleep. On the contrary, the sleep quality did not improve. Age, weight, apnea index are not predictive factors influencing the result of UPPP. Even if UPPP has a relatively poor success rate it still should be proposed to patients suffering from sleep apnea syndrome as it remains the simplest and best tolerated surgical treatment. PMID- 8470553 TI - The results of inferior and middle meatal antrostomy under endoscopic control. AB - Inferior and middle meatal antrostomy have been used for over a century in the treatment of chronic rhinosinusitis. The historical, pathophysiological and clinical aspects of the two approaches are discussed to compare the advantages and disadvantages of each. Whilst surgery in the inferior meatus is relatively safe, it does not address the underlying pathophysiology of the condition in contrast to achieving maxillary ostial function which consequently offers better surgical results. PMID- 8470554 TI - Indications, technique and results of endonasal endoscopic ethmoidectomy. AB - Endoscopic ethmoid sinus surgery was introduced in Erlangen in 1976. Posterior-to anterior ethmoidectomy under the optical control of a 70 degrees telescope with a suction-irrigation handpiece was established for treatment of chronic-diffuse hyperplastic paranasal sinusitis. This technique complements partial resections of the ethmoid. The different procedures are applied depending upon the extent of the disease. The indication for endonasal endoscopic surgery was expanded with practical experience. Diseases of the nasolacrimal duct and the frontal sinus, the frontal skull base as well as the orbita often proved to be accessible for endonasal surgery. A survey of the technical aspects of endoscopic ethmoid surgery and an introduction of the extended range of indications are presented together with the results of each procedure. PMID- 8470555 TI - Assessment of nutrient intake and associated factors in an Indian elderly population. AB - A group of 420 elderly people (163 women and 257 men with a mean age of 65 years) from urban and rural populations in India were selected for the study. The caloric intake of 93.3% was less than the recommended allowance, the mean daily caloric intake being 1191 kcal in men and 928 kcal in women. Except for calcium, all nutrients were deficient in their diet. Illiteracy (53%), lack of knowledge regarding daily allowances of nutrients (95%), poor economic background (46.7%), and breaking down of joint family system (63%) were possible associated factors examined. PMID- 8470556 TI - Expressed wish to die and mortality in older people: a community replication. AB - Three-year mortality of 1063 community residents aged 65 and over interviewed with the Geriatric Mental State Schedule was analysed to examine the influence of specific depression symptoms and physical illness in order to test theoretical predictions from models proposed by Macdonald and Dunn, and by Jorm and colleagues. Expressed wish to die was confirmed as a predictor of mortality, controlling for age, sex, and cognitive impairment. The suggestion that the effect of depressive symptoms on mortality might be a masked effect of physical illness was not confirmed. In general the more specific severe symptoms were better predictors of mortality. PMID- 8470557 TI - Water balance in elderly people: is there a deficiency of vasopressin? AB - Since elderly people are prone to develop both hypo- and hyper-natraemia, we have investigated the biochemical and hormonal responses to overnight (9 h) abstinence from fluids and subsequent oral water load (20 ml/kg) in a group of healthy elderly (E) (mean age 68 years) and young (Y) (mean age 28 years) volunteers. The elderly subjects had significantly higher baseline plasma osmolality (E 293.5 +/- 0.5, Y 290.5 +/- 0.8 mOsm/kg, p < 0.05) but lower urinary osmolality (E 508 +/- 47, Y 842 +/- 52 mOsm/kg, p < 0.001) and lower plasma vasopressin (E 0.5 +/- 0.1, Y 2.3 +/- 0.6 pmol/l, p < 0.001) than the young. There was a significant difference in the mode of excretion, particularly maximum free water clearance (E 6.0 +/- 0.6, Y 10.1 +/- 0.8 ml/min) but no difference in the overall ability to excrete the water load (at 4 h E 93 +/- 8%, Y 92 +/- 5%, p > 0.05). The biochemical and hormonal results suggest that the elderly subjects were in a state similar to partial cranial diabetes insipidus which may predispose them to dehydration and hypernatraemia. The reduction in maximum free water clearance may predispose them to hyponatraemia if excess fluid is administered. PMID- 8470558 TI - Is there a right age for case finding in elderly people? AB - If age is a useful basis for determining a screening policy the benefit of the resulting interventions should vary with age. The choice of the screening age will be such as to maximize the benefit. Data from a study of the screening of elderly people by a Health Visitor produced no evidence to support the choice of 75 as minimum age for screening in primary care. Indeed there was a suggestion that age might be more useful as a maximum rather than a minimum criterion. PMID- 8470559 TI - Subtypes of overactive bladder in old age. AB - The prevalence of urinary incontinence increases dramatically with age and is mainly related to urge incontinence and bladder overactivity. It is a reasonable hypothesis that bladder overactivity primarily results from a disturbed central neuronal control of the lower urinary tract. Different sites and extents of neurogenic lesions or dysfunctions should result in different functional and urodynamic characteristics. We have recently identified three distinct urodynamic subtypes of bladder overactivity, and we report a retrospective study of the distribution of these subtypes in elderly patients. Eight hundred and fourteen patients aged 65 years or older with symptoms of urgency and/or urge incontinence underwent cystometry and the ice-water test. Two hundred and sixty-seven of them (33%) presented an overactive bladder. The prevalence of overactive bladder was constant up to the age of 65. A marked increase above this age was almost entirely ascribed to an increase of the so-called uninhibited overactive bladder subtype. This dysfunction occurred in 70% of the older patients. Patients with this condition have a coordinated reflex micturition at normal bladder volumes, but an abnormal perception of bladder fullness and lack of voluntary inhibitory control. This constellation of symptoms and signs indicates a suprapontine dysfunction. PMID- 8470560 TI - Resting energy expenditure in relation to energy intake in patients with Alzheimer's disease, multi-infarct dementia and in control women. AB - Energy intake and resting energy expenditure in relation to body composition were studied in female patients with Alzheimer's disease, multi-infarct dementia and in home-living non-demented elderly women. Patients with Alzheimer's disease tended to have lower body weight and higher energy intake (p = NS) than control subjects or patients with multi-infarct dementia. Resting energy expenditure did not differ significantly between the groups (1089 +/- 129 kcal/day for patients with Alzheimer's disease, 1078 +/- 102 kcal/day for patients with multi-infarct dementia and 1188 +/- 143 kcal/day for control women; mean +/- SD). Energy expenditure did not differ between the groups when calculated in relation to body weight or lean body mass. In institutionalized female patients with long-standing Alzheimer's disease the resting energy expenditure was not increased, but they tended to have low body weight despite a high energy intake. PMID- 8470561 TI - Review: Alzheimer's disease and environmental aluminium. PMID- 8470562 TI - Age and susceptibility to pneumococcal infection. PMID- 8470563 TI - Metabolic switches in ageing. PMID- 8470564 TI - The influence of urinary incontinence on the quality of life of elderly women. AB - The quality of life assessed by the Nottingham Health Profile Questionnaire was compared in a group of women (n = 120) suffering from urinary incontinence (age 75.4 +/- 1.9, range 65-84 years) and an age-matched representative sample of the total population (n = 313). There were no significant differences between the two groups of women in occurrence of other illnesses or social characteristics. Women suffering from urinary incontinence obtained higher scores in the domains of emotional disturbances (p < 0.05) and social isolation (p < 0.001) than women from the control group. When subdividing the incontinent women by type of incontinence it was found that women suffering from urge and mixed incontinence reported emotional disturbances (p < 0.05) more than women from the control group. There was, however, no difference within the domain of emotional disturbances between stress-incontinent women and the control group. Women suffering from urge incontinence reported more disturbance of sleep (p < 0.05) than the control group. Women suffering from all types of urinary incontinence (p < 0.05) were socially more isolated than those from the age-matched group of women from the total population. Urinary incontinence in women has a detrimental effect on their daily lives and causes them to avoid social contacts. PMID- 8470565 TI - The energetic cost of some daily activities: a comparison in a young and old population. AB - We compared the energetic costs of some daily activities in two groups, 10 young people (24.3 +/- 2.8 years) and 10 old people (74.4 +/- 2.2 years): rising and sitting back down on a seat, getting up from and lying down on a bed and getting up from the floor. We measured the oxygen consumption and the time necessary for the activities. The results showed a noteworthy economical energetic procedure when rising and sitting back down on a seat among the older group. The values of the energy expenditure were respectively 3.9 +/- 1.3 cal/kg in the older group and 5.8 +/- 1.6 in the younger one with a standard seat (45 cm) and 2.7 +/- 1.2 vs 5.2 +/- 1.5 with a raised seat (60 cm). The activities did not vary significantly in time in the two age groups. This procedure could be understood as an adaptation of the energy expenditure to the reduced aerobic capacity with ageing. Conversely, getting up from and lying down on the floor or a standard hospital bed involved the same energy expenditure in the older and younger group, but performing these activities took significantly longer for the older people (+60% for getting up from the floor, +33% from the bed). As these activities revealed no economical energetic procedure in the older group, they appeared responsible for a strong factor of dependence. The importance of a learning process particularly for the most usual movements in everyday life is discussed. PMID- 8470566 TI - Hospital admissions for asthma in Finland during 1972-86 of adults aged 65 years and over. AB - The aim of this investigation was to examine the use of hospital services, on account of asthma, among adults aged 65 and over in 1972-86. According to the discharge records maintained by the National Board of Health, asthma caused a total of 710,187 hospitalization days and 62,342 periods of hospital treatment among elderly people during the 15 years concerned. The annual number of hospitalization days per 100,000 persons, standardized for age and sex, was 8438 and that of treatment periods 731. The figures were higher in the case of patients under 75 years than with older age groups, but it was in the oldest age groups that the numbers of treatment periods increased most. The mean duration of a treatment period decreased from 15.4 days to 9.6 days in the course of the 15 years, but became longer with increasing age. The 15 years of consistently recorded data on asthma patients point to an increase in the use of hospital services by elderly people and suggest that the diagnosis and treatment of asthma in this sector of the population will pose a challenge for the health service in the future. PMID- 8470567 TI - Prevention of barium aspiration during videofluoroscopic swallowing studies: value of change in posture. AB - OBJECTIVE: We investigated the frequency with which changes in the position of a patient's head or body eliminated aspiration of liquid barium during videofluoroscopic swallowing studies in patients with oropharyngeal dysphagia. We also studied factors that influenced the effect of posture on aspiration. SUBJECTS AND METHODS: The study group comprised 165 patients consecutively referred for videofluoroscopic examination of the oropharyngeal stages of swallowing in whom aspiration of barium occurred while swallowing 1, 3, 5, or 10 ml of thin liquid barium or drinking barium from a cup. When aspiration occurred, the patient changed to one of five postures (chin down, chin up, head rotated, head tilted, and lying down), selected on the basis of the specific swallowing abnormality causing the aspiration. RESULTS: Changes in head or body position eliminated aspiration of at least one bolus of barium in 127 (77%) of the 165 patients, and of all four boluses plus drinking barium from a cup in 41 patients (25%). Postural changes were less beneficial in preventing aspiration in patients with substantial language or cognitive defects or restricted head movement. CONCLUSIONS: Postural techniques can eliminate aspiration of barium of at least small volumes in most patients. Expansion of the oropharyngeal swallowing study to include the effect of various postures can be done with minimal risk of increased aspiration. PMID- 8470568 TI - Value of T1 and T2 relaxation times from echoplanar MR imaging in the characterization of focal hepatic lesions. AB - OBJECTIVE: The purpose of this study was to determine the value of echoplanar imaging in characterizing focal hepatic lesions on the basis of image-derived T1 and T2 relaxation times. SUBJECTS AND METHODS: Forty-six proven hepatic lesions were analyzed: 24 solid (21 metastases, three primary liver tumors) and 22 nonsolid (11 hemangiomas and 11 cysts). Mean lesion size (maximal length) was 4.0 (+/- 3.2) cm, and 16 of 46 lesions were less than 2.0 cm. A commercially available 1.5-T echoplanar-equipped MR scanner was used to obtain fat-suppressed, single-excitation (TR essentially infinite) axial images with a slice thickness of 10 mm. T1-weighted inversion recovery images (TE = 25 msec; TI = 100, 380, 600, or 800 msec) were acquired for 28 of 46 lesions, and T2-weighted spin-echo images (TE = 25, 50, 100, 75 or 150 msec) were acquired for 45 of 46 lesions. For each acquisition (i.e., each different TI or TE), the entire liver was imaged in a single breath-hold of 12 sec or less. RESULTS: The mean T1 was 1004 (+/- 234) msec for solid lesions, 1337 (+/- 216) msec for hemangiomas, and 3143 (+/- 1392) msec for cysts. Although the mean T1 of solid and nonsolid lesions differed (p < .004), overlap precluded the use of T1 as a discriminatory index. Mean T2 times were 80 (+/- 18) msec for solid lesions, 178 (+/- 40) msec for hemangiomas, and 517 (+/- 429) msec for cysts. The mean T2 for hemangiomas is the longest reported to date. A T2 cutoff of 116 msec was 100% accurate for classifying lesions as solid or nonsolid and 93% accurate for characterizing them as benign or malignant. CONCLUSION: Our study suggests that echoplanar-derived T2 times (but not T1 times) are useful for characterizing focal hepatic lesions. An important use may be to characterize small lesions measuring less than 2.0 cm. The main advantages of echoplanar imaging are the absence of motion-induced volume averaging and phase artifacts, the ability to acquire purely T2-weighted images, and the use of multiple data points to calculate relaxation times. PMID- 8470569 TI - Traumatic laceration of the liver limited to the bare area: CT findings in 25 patients. AB - OBJECTIVE: The capsular extent of traumatic hepatic lacerations may be limited to the bare area of the liver--an area not covered by peritoneal reflection. In these cases, intraperitoneal bleeding may not occur, classic peritoneal findings may be absent, and results of diagnostic peritoneal lavage may be normal. We undertook a study to evaluate the frequency, CT appearance, and significance of injury of the bare area of the liver. MATERIALS AND METHODS: We retrospectively reviewed radiologic reports of 1469 hemodynamically stable trauma patients referred for abdominal CT between January 1986 and September 1992 and selected 155 patients whose CT reports indicated hepatic injury. Retrospective review of the abdominal CT scans of these 155 patients confirmed intrahepatic laceration or contusion in all of them. The study involved the 25 (16%) patients in whom the capsular extent of injury was limited to the bare area of the liver. RESULTS: In all cases, CT scans showed simple or complex lacerations involving predominantly or exclusively the posterior segment of the right hepatic lobe, with capsular extent limited to the superomedial hepatic surface. Abnormal retroperitoneal findings were present in all but two cases. Twenty-two (88%) of 25 patients had right-sided retroperitoneal hemorrhage or fluid collections; adrenal hematoma or periadrenal fluid was seen in 12 (48%) patients. Abnormal pericaval fluid collections were present in nine (36%). Only five (20%) patients had free intraperitoneal fluid. Diagnostic peritoneal lavage, performed as a correlative procedure in four patients, revealed intraabdominal hemorrhage in one, equivocal findings in one, and normal findings in two. Patients who had isolated injuries of the bare area of the liver did well clinically and were discharged after an uneventful hospital stay of an average of 3 days (range, 2-7 days). CONCLUSION: A small percentage of hemodynamically stable patients who have hepatic trauma may have lacerations that primarily involve the bare area and that are not suspected clinically or detected by diagnostic peritoneal lavage. In these patients, CT may be helpful to show the extent of liver injury, identify associated retroperitoneal abnormalities, and provide prognostic information. PMID- 8470570 TI - Complications after laparoscopic cholecystectomy: imaging findings. AB - Laparoscopic cholecystectomy is rapidly becoming an acceptable alternative to traditional open cholecystectomy. Laparoscopic procedures are associated with shortened recovery periods and hospital stays and the cosmetic benefit of smaller scars. Early results from laparoscopic cholecystectomies suggested a high rate of complications; however, recent studies have shown that, in experienced hands, the complication rates of open and laparoscopic procedures are comparable. Complications differ somewhat between the two types of operations. In laparoscopic cholecystectomy, complications are associated with virtually every aspect of the procedure. The purpose of this essay is to illustrate the imaging findings of the complications that occur in patients undergoing laparoscopic cholecystectomy. PMID- 8470571 TI - Posterior superior pancreaticoduodenal vein: mimic of distal common bile duct at sonography. AB - OBJECTIVE: Previous investigators have noted that the common bile duct may appear to merge with the portal vein on sagittal sonograms, mimicking a venous structure. The posterior superior pancreaticoduodenal vein courses adjacent to the distal part of the common bile duct within the pancreatic head. A prospective study was performed to assess the sonographic appearance of the posterior superior pancreaticoduodenal vein. SUBJECTS AND METHODS: The study included 50 consecutive subjects in whom the pancreatic head was well seen. Anatomic characteristics of the posterior superior pancreaticoduodenal vein were noted with gray-scale, duplex Doppler, and color Doppler sonography. The site of insertion of the posterior superior pancreaticoduodenal vein into the portal vein was noted. RESULTS: The posterior superior pancreaticoduodenal vein was visualized in all 50 cases. Although it usually (82% of cases) inserted into the posterior aspect of the portal vein, the posterior superior pancreaticoduodenal vein inserted into the anterior aspect of the portal vein in nine cases (18%), resulting in an appearance mimicking the common bile duct on sagittal sonograms. Doppler examination showed flow toward the portal vein in all obliquely oriented posterior superior pancreaticoduodenal veins, and in 40% overall. The common bile duct could always be followed into the porta hepatis and was anterior to the posterior superior pancreaticoduodenal vein in 49 cases (98%). CONCLUSION: The posterior superior pancreaticoduodenal vein can be seen routinely on sonograms when the pancreatic head is unobscured, and it can mimic the common bile duct in a significant number of cases. These structures can be distinguished by noting continuation of the common bile duct into the porta hepatis, the generally anterior position of the common bile duct, and flow in the posterior superior pancreaticoduodenal vein on Doppler examination. Awareness of the existence and anatomy of the posterior superior pancreaticoduodenal vein minimizes its confusion with the common bile duct at sonographic examination. PMID- 8470572 TI - Mucin-producing adenoma of the appendix. PMID- 8470573 TI - Epidermoid cyst of the testicle: an unusual sonographic finding. PMID- 8470574 TI - Detection of multiple myeloma involving the spine: efficacy of fat-suppression and contrast-enhanced MR imaging. AB - OBJECTIVE: To determine the efficacy of fat-suppressed sequences and contrast enhanced MR imaging for the detection of focal spinal lesions caused by multiple myeloma, we obtained MR images in 32 patients with newly diagnosed myeloma who had back pain. SUBJECTS AND METHODS: All patients had biopsy-proved myeloma and had MR imaging at the painful level of the spine. Spin-echo T1-weighted, T2 weighted, and short TI inversion-recovery (STIR) images; dynamic ultrafast low angle shot (turbo-FLASH) images after IV injection of a bolus of paramagnetic contrast material; and contrast-enhanced T1-weighted images were obtained. We qualitatively compared the signal intensities and contrast enhancement of focal lesions with those of the surrounding vertebral bodies. RESULTS: Multiple lesions were detected in all but two of the 32 patients. On T2-weighted and STIR images, all lesions had homogeneously high signal intensity. On T1-weighted images, the lesions were visible as hypointense areas compared with surrounding bone in all except four patients, in whom the lesions were isointense or hyperintense. All tumor nodules enhanced on turbo-FLASH images obtained in the arterial phase. No additional lesions were seen on STIR or contrast-enhanced images. MR findings resulted in a change in the staging of the disease in one patient and led to prompt treatment in five patients with epidural involvement. CONCLUSION: MR imaging appears to be helpful in detecting spinal involvement in patients with multiple myeloma. The diagnosis of spinal lesions is best achieved by using either fat-suppressed or T2-weighted images. Although myeloma lesions enhanced in all patients, contrast material appears to be of no value for the detection of additional lesions. PMID- 8470576 TI - MR imaging of the sacral plexus: normal findings. AB - Imaging of the sacral plexus requires evaluation of both intradural and extradural components with cross-sectional techniques. Although CT is useful, individual extradural sacral nerves and the sacral plexus usually cannot be distinguished from adjacent structures. The higher contrast resolution provided by MR imaging allows the region of the sacral plexus to be examined in greater detail. With MR imaging, the constant relationship of the neural components to one another, and the gluteal vessels in their course from the sacrum to the greater sciatic foramen, can be shown consistently. An understanding of the anatomy of this area in multiple planes can aid in more accurate localization of abnormalities involving the sacral plexus. This pictorial essay reviews the MR appearance of the region of the sacral plexus. PMID- 8470575 TI - MR appearance of multiple myeloma of the spine before and after treatment. AB - OBJECTIVE: The aim of this study was to describe the changes in the MR appearance of painful lesions of the spine before and after treatment in 18 patients with multiple myeloma and to correlate these changes with the clinical response to treatment. SUBJECTS AND METHODS: Eighteen patients with multiple myeloma and tumor nodules in the spine had MR imaging of the same site in the spine before and after treatment. Unenhanced T1- and T2-weighted spin-echo images, dynamic ultrafast low-angle shot (turbo-FLASH) images before and after IV bolus injection of paramagnetic contrast material, and contrast-enhanced T1-weighted spin-echo images were obtained. Characteristic signal and contrast enhancement before and after treatment were compared and were correlated with clinical data and the results of immunochemical and pathologic tests. RESULTS: Changes in signal intensity and enhancement of the lesions occurred after treatment in 14 of 18 patients. The characteristics of the lesions after treatment had three patterns: (1) rim enhancement or no enhancement of the lesions, (2) early enhancing lesions associated with other nonenhancing lesions or lesions with rim enhancement, and (3) no change from the enhancement pattern seen before treatment. In 13 of 18 patients, these patterns correlated well with the response to treatment. A discrepancy was observed in five patients. CONCLUSION: The MR appearance of spinal myeloma is different before and after treatment. MR images, particularly contrast-enhanced images, may be helpful in monitoring the response to treatment of focal bone lesions of myeloma. PMID- 8470577 TI - MR imaging of the sacral plexus: abnormal findings. AB - Patients with symptoms of sacral plexopathy, radiculopathy, or sciatica may have disease originating in the neural elements, sacrum, bony pelvis, pelvic soft tissues, or gluteal region. As illustrated in our companion article, the sacral plexus and surrounding structures can be visualized in detail with MR imaging. This pictorial essay illustrates the MR findings in a number of abnormalities affecting the sacral plexus. Multiplanar MR examination is particularly helpful in defining neural levels of involvement by disease in this region. PMID- 8470578 TI - Calcific myonecrosis of the calf manifesting as an enlarging soft-tissue mass: imaging features. PMID- 8470579 TI - Scaphoid dislocation with radial-axial carpal disruption. PMID- 8470580 TI - Embolic cerebral infarction: MR findings in the first 3 hours after onset. AB - OBJECTIVE: MR imaging has a high sensitivity for detecting ischemic brain parenchyma. The aim of this study was to evaluate the changes in the signal intensity of infarcted brain parenchyma on MR images obtained within the first 3 hr after the onset of signs and symptoms in patients with embolic cerebral infarction. MATERIALS AND METHODS: We studied MR images of 16 patients who had a diagnosis of embolic cerebral infarction (highly probable according to criteria of the National Institute of Neurological and Communicative Disorders and Stroke). T1-weighted, T2-weighted, and proton density-weighted MR images were obtained within 3 hr after the onset of symptoms. Two neuroradiologists who had no knowledge of the diagnoses reviewed the MR images of these 16 patients and 20 control subjects in random order and evaluated signal-intensity changes in the gray and white matter. RESULTS: On proton density-weighted images, the central and cortical gray matter showed increased signal intensity in 63-69% and 88-94% of the patients, respectively. No abnormalities of the brain parenchyma were apparent on T1-weighted and T2-weighted images obtained within 3 hr after the onset of symptoms. The adjacent white matter appeared hyperintense on long TR images in only a few cases. CONCLUSION: An increased signal intensity in the gray matter on proton density-weighted images was the most characteristic parenchymal change seen on MR images of the brain obtained within 3 hr after embolic cerebral infarction. PMID- 8470581 TI - Meningiomas involving the cavernous sinus: value of imaging for predicting surgical complications. AB - OBJECTIVES: The purpose of this study was to determine if it is possible to predict complications of surgery on cavernous sinus meningiomas on the basis of preoperative MR and CT findings. MATERIALS AND METHODS: We retrospectively reviewed the CT, MR, and postoperative clinical findings in 65 consecutive patients with pathologically proved cavernous sinus meningiomas who had surgery during the period 1985-1991. Tumors were categorized on the basis of their relationship to the cavernous carotid artery. The presence of tumor in three anatomic sites (the sella, the sphenoid sinus, and the orbital apex) was also correlated with surgical complications. RESULTS: Category 1 tumors, which do not completely encircle the cavernous carotid artery, were dissected without injury, sacrifice, or grafting of the artery in 91% of cases. Category 2 lesions completely encircle the artery but do not narrow its lumen; they could be dissected from the cavernous carotid artery without arterial injury in 61% of cases, but imaging failed to discriminate differences within this group. Category 3 lesions, which completely encircle and narrow the cavernous carotid artery, are usually difficult to dissect free from the artery. The categories also correlated with recovery of extraocular motility; 84% of category 1 lesions compared with only 36% of category 2 or 3 lesions will recover to good or excellent extraocular motility after cavernous sinus surgery. Tumor involvement of the sella, orbital apex, and sphenoid sinus correlated with postoperative endocrine dysfunction, decreased visual acuity, and CSF leak, respectively. CONCLUSION: Imaging studies can frequently predict the difficulty of resecting cavernous sinus meningiomas from the cavernous carotid artery and the likelihood of permanent loss of extraocular motility after surgery on these lesions. This information is helpful in appropriate preoperative planning and in providing information to patients about to undergo such surgery. PMID- 8470582 TI - Mesenrhombencephalitis: MR findings in nine patients. AB - OBJECTIVE: Mesenrhombencephalitis is a serious form of brainstem inflammation predominantly involving the deep and vital portions of the brain, that is, the mesencephalon (midbrain) and rhombencephalon (pons, medulla). Mesenrhombencephalitis is difficult to diagnose on the basis of clinical and laboratory findings alone, and access to this portion of the brain for surgical biopsy carries high morbidity. We describe the MR appearance of mesenrhombencephalitis and correlate the imaging findings with clinical information. MATERIALS AND METHODS: Unenhanced and contrast-enhanced MR images of nine patients with mesenrhombencephalitis were reviewed retrospectively and correlated with clinical, laboratory, and pathologic data. The patients were categorized according to the cause of the disease: three had herpes simplex, one had Listeria monocytogenes, and five had mesenrhombencephalitis of undetermined cause. The three patients with clinical and MR evidence of herpes simplex mesenrhombencephalitis (one confirmed by brain biopsy) were comatose at presentation, with cranial nerve abnormalities in two and seizures in one. One patient with L. monocytogenes (established by blood culture) had cranial nerve palsies, fever, and pain in the ear. Five additional patients had headache (three), fever (three), nausea and vomiting (four), cranial nerve palsies (three), coma (two), and hyporeflexia (one) or hyperreflexia (four). Brain biopsy performed in two patients revealed chronic inflammation of unspecified cause; in one, it was compatible with viral encephalitis. RESULTS: MR images in three patients with herpes simplex mesenrhombencephalitis showed T2 signal hyperintensity in the midbrain (two), pons (one), medulla (one), and temporal lobes (three). Parenchymal foci of hemorrhage (methemoglobin, one patient) and leptomeningeal enhancement (one patient) were identified in the temporal lobes. T2-weighted MR images in one patient with L. monocytogenes showed signal hyperintensity in the brainstem, vermis, midbrain, and internal capsules. On T1 weighted images, low signal was present in these areas, which enhanced with paramagnetic contrast agents. In the remaining five patients, T2-weighted MR images showed patchy signal hyperintensity in the pons, medulla, and thalamus in three each and in the midbrain and temporal lobes in one each. T1-weighted MR images showed normal findings (two) or signal hypointensity in the thalamus and pons in one patient each. Areas of leptomeningeal and parenchymal enhancement were identified in one patient each. Brainstem swelling was seen in three patients, one of whom had petechial hemorrhage in the pons and hydrocephalus. CONCLUSION: Mesenrhombencephalitis is a serious illness that is diagnosed by a combination of imaging, clinical, laboratory, and pathologic studies. MR imaging may be crucial to the early diagnosis of this illness, and radiologists must be familiar with this uncommon entity and its MR findings in order to make timely diagnoses and facilitate treatment. PMID- 8470583 TI - Advice for Latin lovers. PMID- 8470584 TI - Lesions causing a mass in the medial canthus of the orbit: CT and MR features. AB - Few detailed radiologic articles treat the medial canthus as a "compartment" of the orbit. Nasal stuffiness and epiphora (excessive tearing) are frequent clinical manifestations of diseases involving the medial canthus of the orbit. Although some lesions can be adequately evaluated by clinical examination, imaging may show unsuspected deep extensions of the abnormality. CT has traditionally been the imaging method of choice because of the inherent contrast between structures in this region and its superb depiction of bone detail (Fig. 1). MR imaging can be useful in detecting subtle marrow invasion caused by lesions extending beyond the confines of the medial canthus (e.g., frontal bone, maxilla). In this pictorial essay, we illustrate the CT and MR appearances of diseases that can manifest as a medial canthal mass and provide practical differential diagnoses. Lesions can be inflammatory, neoplastic, or developmental in origin. Moreover, these lesions can result from abnormalities in the adjacent nasolacrimal apparatus, orbit, paranasal sinuses, and nasal cavity, or they can reflect an underlying systemic illness. PMID- 8470585 TI - Pneumatization of the paranasal sinuses: normal features of importance to the accurate interpretation of CT scans and MR images. AB - CT and MR imaging of the paranasal sinuses in infants and children reveal a spectrum of findings associated with the normal pneumatization process, both inside the sinus cavities and in the adjacent marrow spaces. These normal findings must be understood and recognized so that CT scans and MR images may be accurately interpreted. If such normal developmental radiologic findings are not appreciated, misinterpretation may occur and lead to inappropriate treatment. In this pictorial essay, the normal process of pneumatization for each paranasal sinus group will be described from the first stages of the process to its completion. CT scans and MR images will illustrate the range of normal radiologic findings associated with the developmental process, with emphasis placed on the types of findings that, although normal, create potential interpretive difficulties. PMID- 8470586 TI - Necrosis of the putamen caused by methanol intoxication: MR findings. PMID- 8470587 TI - Volume of the spleen in children as measured on CT scans: normal standards as a function of body weight. AB - OBJECTIVE: The purpose of this study was to develop standards for the normal volume of the spleen in children as measured on CT scans. SUBJECTS AND METHODS: CT scans were used to measure the volume of the spleen in 48 children (30 boys and 18 girls), 1 day to 18 years old (mean and median ages were 8.2 and 7.8 years, respectively). Children who had underlying malignant tumors, infection, hematologic diseases, or other conditions that could alter splenic size were excluded. The area of the spleen on each axial section was determined by tracing its outline on the CT monitor and measuring the area of the region of interest. The area of the spleen on each section was multiplied by the slice thickness to calculate the volume of the spleen for each section. The total volume of the spleen was then determined by adding the individual volumes for each of the sections through the spleen. This method of calculating splenic volume has been validated in previous studies in adult subjects. The volume of the spleen was analyzed as a function of both body weight and age. RESULTS: The volume of the spleen correlated better with body weight than with age. The best regression model (r = .85) was a linear relationship as follows: splenic volume (cm3) = 0.7 + [4.6 x weight (kg)]. Using these data and a regression model, we generated standards for normal volume of the spleen as a function of body weight (with 95% tolerance intervals). CONCLUSION: We have developed CT standards for normal splenic volume in children. These standards can be used to objectively measure the size of the spleen in children who have clinically suspected splenomegaly. PMID- 8470588 TI - Malignant meningioma in a child: CT and MR findings. PMID- 8470590 TI - Needle-stick injuries and blood contacts during invasive radiologic procedures: frequency and risk factors. AB - OBJECTIVE: Possible nosocomial transmission of blood-borne pathogens is a serious concern for health care workers and patients alike. Needle-stick injuries and blood contacts pose a risk of pathogen transmission during procedures. We performed a study to determine the frequency of injuries and blood contacts during invasive radiologic procedures and to examine procedure-related factors that may increase risk of injury or exposure. SUBJECTS AND METHODS: A prospective study of needle-stick injuries and blood contacts during invasive radiologic procedures was performed. During a 10-week period, information about procedures was recorded by technologists or physicians, and needle-stick injuries and exposures to patients' blood and body fluids were noted. Data were analyzed with the SAS statistical package. RESULTS: Accidental exposure to patients' blood and body fluids occurred in 15 of 501 cases (3.0%; 95% confidence interval, 1.7 4.9%). Of 729 operators at risk, 15 were exposed (2.0%; 95% confidence interval 1.1-3.3%). Exposure was parenteral in one case and cutaneous in 14. Risk of exposure was correlated with procedure duration (p = .003), but not with emergency vs elective procedure status (p = .796), procedure type (p = .275), or operator experience level (p = .554). Three needle-stick injuries (0.6% of cases) occurred, all with sterile instruments; bleeding occurred in two cases. Risk of injury was correlated only with procedure type (p = .046). In no case was a patient exposed to a physician's blood. CONCLUSION: Whereas cutaneous exposure of physicians to patients' blood was not infrequent, parenteral exposure was rare in this series. Most of the exposures in this study could have been prevented by the use of protective equipment. Patients' contact with physicians' blood did not occur in this study. PMID- 8470589 TI - Volumetric flow rates in the portal venous system: measurement with cine phase contrast MR imaging. AB - OBJECTIVE: The purposes of this study were to (1) validate the accuracy of cine phase-contrast MR flow measurements within the portal vein, (2) develop a suitable protocol for using this method to measure volumetric flow rate in the portal venous system, and (3) use this protocol, with Doppler sonography as a reference, to measure portal venous flow in healthy volunteers and in patients with protal venous hypertension. SUBJECTS AND METHODS: Flow determinations were obtained in a model of fluid movement approximating blood-flow conditions in the portal venous system. A suitable protocol was based on consideration of the theoretical effects of (1) spatial resolution, (2) obliquity of the imaging plane to the direction of flow, and (3) signal-to-noise ratio of the signed quantitative velocity images (in three volunteers) on the accuracy and precision of flow measurements. This protocol was used to obtain cine phase-contrast MR images of the portal venous system in five volunteers and six patients. RESULTS: Values obtained with a flow phantom showed good accuracy of cine phase-contrast measured vs actual volumetric flow rate (r = .995; p = .0001; MR rate = [0.94 x actual rate] + 65.6 ml/min; standard error of the y estimate = 67.3 ml/min). Velocity encoding and section thickness substantially influenced the signal-to noise ratio of the velocity images, whereas flip angle and matrix size had only minimal effect. In volunteers and patients, portal volumetric flow rates determined by using MR images and Doppler sonography showed good correlation (r = .94; p = .0003). CONCLUSION: Our results indicate that cine phase-contrast MR imaging is a practical noninvasive method for measuring volumetric flow rates in the portal venous system. PMID- 8470591 TI - Collapse of a Palmaz stent in the subclavian vein. PMID- 8470592 TI - Leiomyosarcoma of the femoral vein: imaging findings. PMID- 8470593 TI - Implantation of P.A.S. Port venous access device in the forearm under fluoroscopic guidance. PMID- 8470594 TI - Cutaneous T-cell lymphoma: value of CT in staging and determining prognosis. AB - OBJECTIVE: The usefulness of CT in diagnosing, staging, and establishing the prognosis in cutaneous T-cell lymphoma was assessed. CT abnormalities indicative of the disease, diffuse peripheral adenopathy and skin lesions, as well as less specific signs of generalized lymphoma, were correlated with clinical findings. MATERIALS AND METHODS: The study group comprised 33 patients from a total of 87 with pathologically proved cutaneous T-cell lymphoma who were seen at the University of Pittsburgh Medical Center between 1986 and 1991 and who had CT scans. All patients had body CT imaging with contiguous axial sections no thicker than 10 mm of the chest, abdomen, and pelvis; other CT studies were performed as clinically indicated. Because of the cutaneous nature of this lymphoma, collimation included the skin surface. RESULTS: In 10 of the 33 patients, all of whom had stage II or higher disease, abnormalities indicative of cutaneous T-cell lymphoma were seen on CT scans. All 10 had multiple areas of focal skin thickening or plaques several centimeters or more in diameter and 5 mm or greater in thickness affecting the dermal tissues while leaving the subcutaneous fat intact. Extension of individual lesions below the dermis was associated with the development of squamous cell cancers in two patients, both of whom had previous topical therapy. Seven of the 10 also had an unusual pattern of lymphadenopathy: the mediastinum or paraaortic regions were spared while enlarged peripheral nodes were seen in both the axillary and inguinal areas. Skin abnormalities were seen on CT scans of all patients with lymphadenopathy. CONCLUSION: CT findings in cutaneous T-cell lymphoma are related to the pathophysiology of the disease: cutaneous plaques and diffuse peripheral adenopathy that spare the mediastinal and paraaortic lymph nodes. Although the skin lesions can be easily evaluated clinically, secondary malignant neoplasms arising in treated skin lesions can be found with CT by their extension into the subcutaneous fat. PMID- 8470595 TI - AIDS-related non-Hodgkin's lymphoma: abdominal CT findings in 112 patients. AB - OBJECTIVE: Non-Hodgkin's lymphoma is a common complication in patients with HIV infection. The purpose of this study was to analyze the abdominal CT findings in a large series of patients with this condition. MATERIALS AND METHODS: We retrospectively reviewed the abdominal CT examinations of 110 men and two women (21-62 years old; average, 39 years) with untreated AIDS-related lymphoma, as defined by the Centers for Disease Control. Lymphoma was the initial AIDS defining illness in 79% of the patients. RESULTS: Abdominal CT scans showed normal findings or only mild enlargement of the liver or spleen in 36% of the 112 patients, whereas evidence of intraabdominal lymphoma was seen in 64%. Evidence of focal lymphomatous involvement was seen on abdominal CT scans in 58 (98%) of 59 patients in whom the predominant signs and symptoms were related to the abdomen and in 14 (26%) of 53 patients with extraabdominal signs or symptoms. In the 64% of patients with evidence of intraabdominal lymphoma, lymph node enlargement was seen in 56% and extranodal disease was seen in 86%. Extranodal sites of involvement in the 72 patients with evidence of intraabdominal lymphoma included the gastrointestinal tract (54%), liver (29%), kidney (11%), adrenal gland (11%), lower genitourinary tract (10%), spleen (7%), peritoneum and omentum (7%), pancreas (5%), epidural space (4%), bone (3%), and muscle (1%). Mild enlargement of the liver or spleen was present in a minority of cases. Moderate or marked hepatomegaly (cephalocaudal span > 20 cm) and splenomegaly (cephalocaudal span > 15 cm) were even less common and occurred only in the presence of focal hepatic lesions. CONCLUSION: Our results show that AIDS-related lymphoma may affect any abdominal organ, most commonly lymph nodes, the gastrointestinal tract, liver, kidney, and adrenal gland. Hepatic or splenic enlargement was uncommon and was not often seen as an isolated finding in the absence of evidence of abdominal lymphoma. PMID- 8470596 TI - Department of Radiology, Massachusetts General Hospital: a brief history. PMID- 8470597 TI - Nominal dysphasia redux. PMID- 8470598 TI - Removing red arrows efficaciously. PMID- 8470599 TI - Calcified pulmonary metastases from a cardiac angiosarcoma. PMID- 8470600 TI - Severe nodulocystic acne causing "ring lesions" on mammograms. PMID- 8470601 TI - Colonic diaphragms associated with long-term use of nonsteroidal antiinflammatory drugs. PMID- 8470602 TI - Small-bowel leiomyosarcoma mimicking urachal carcinoma: CT findings. PMID- 8470603 TI - Visceral calcifications in patients with AIDS. PMID- 8470604 TI - Sonographic demonstration of skeletal muscle invasion by lymphoma. PMID- 8470605 TI - Crossed cerebellar diaschisis and atrophy: the role of intractable seizures. PMID- 8470606 TI - John Caffey Award. Colonic perforation by air and liquid enemas: comparison study in young pigs. AB - OBJECTIVE: Hydrostatic enema reduction of intussusception in children has been replaced by pneumatic reduction in a number of institutions. Colonic perforation occurs in as many as 2.8% of enema reductions, and questions persist about the relative safety of enemas performed with air vs fluid. The objectives of this study were to investigate and compare the pathologic patterns of in vivo colonic perforation and fecal spillage in young pigs given air and hydrostatic enemas, with and without the Valsalva maneuver. MATERIALS AND METHODS: Colonic perforations were induced in 135 juvenile pigs. The pigs were divided into five groups, and enemas with air, barium, and water-soluble contrast material were given with and without the Valsalva maneuver to induce the perforations. During the enemas, the Valsalva maneuver was observed when the animals strained. In each animal, the enema was continued and pressure increased until a perforation was detected with fluoroscopy. Radiographic, gross, and histologic examinations of each animal were performed after perforations occurred. Differences in fecal spillage were noted, and the morphologic variations of the perforations and the surrounding tissue were determined. RESULTS: Perforations with hydrostatic (barium, water-soluble) enemas occurred at approximately 120 mm Hg of pressure (average bag height, 57 in. [143 cm]). No significant variations were found between the type of material used for contrast or the use of the Valsalva maneuver. With air enemas, perforations occurred at a mean pressure of 108 mm Hg without the Valsalva maneuver and at 145 mm Hg with the Valsalva maneuver. Perforations during air enemas did not occur during the Valsalva maneuver (pressures as high as 270 mm Hg), but rather between Valsalva maneuvers. Hydrostatic enemas produced full-thickness tears that were larger than those induced by air enemas in all cases. Air enemas with and without the Valsalva maneuver produced partial-thickness tears in 45% and 10%, respectively, of the pigs. Fecal spillage was diffuse in all hydrostatic perforations. In air enemas, spillage was focal in 55% and 90%, respectively, and absent in 45% and 10%, respectively, of perforations produced with and without the Valsalva maneuver. CONCLUSION: Our results suggest that air enemas are safer than liquid enemas. Perforations that occurred during air enemas were smaller and associated with less fecal spillage and peritoneal contamination. The Valsalva maneuver appears to prevent colonic perforation during air enemas. PMID- 8470607 TI - Medicine in American art. The Agnew Clinic. PMID- 8470608 TI - The role of MR imaging in carcinoma of the urinary bladder. AB - In this article, the role of MR imaging in the management of carcinoma of the urinary bladder is reviewed and illustrated. The appearance of the normal urinary bladder and of bladder carcinoma on MR images is shown. Important factors for optimal MR imaging of urinary bladder carcinoma are reviewed. New developments such as three-dimensional and fast spin-echo sequences and the use of contrast agents, endorectal imaging, and phased array coils are discussed. Finally, the value of MR imaging in the staging of bladder carcinoma is described, and MR staging is compared with clinical staging, staging based on findings from intravesical sonography, and CT staging. PMID- 8470609 TI - MR imaging of the corpus callosum. AB - The corpus callosum is the major axonal commissure of the brain, connecting the two cerebral hemispheres and providing communication between the cortical and subcortical neurons. With MR imaging in the sagittal plane, the corpus callosum can be depicted in great detail. We review the normal anatomy, development, and process of myelination of the corpus callosum. The MR features of various pathologic conditions involving the corpus callosum are described. Finally, we discuss the evolving role of MR imaging in neuropsychiatric diseases with respect to the corpus callosum. PMID- 8470610 TI - Sonography of the upper extremity and jugular veins. AB - Color Doppler sonography is a useful technique for rapid, noninvasive evaluation of venous disease in the upper extremity. It has been used successfully to evaluate thrombosis related to indwelling central catheters. In addition, Doppler sonography shows promise for monitoring thrombolytic therapy after "effort thrombosis" and detecting intermittent venous compression related to thoracic outlet syndrome. PMID- 8470611 TI - MR imaging of the myocardium using nonionic contrast medium: signal-intensity changes in patients with subacute myocardial infarction. AB - OBJECTIVE: Gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York) is a new nonionic MR contrast medium that has been shown in animal studies to provide persistent differential enhancement of myocardial infarction. Because differential enhancement of normal and infarcted myocardium may be useful for the diagnosis and sizing of myocardial infarctions, we assessed the effectiveness of gadodiamide injection in enhancing signal-intensity differences between infarcted and normal myocardium on spin-echo T1-weighted images. SUBJECTS AND METHODS: Signal intensity of normal and infarcted myocardium, contrast ratio, contrast-to noise ratio, and signal-to-noise ratio were measured in 12 patients with subacute myocardial infarction (mean, 16 days after diagnosis) before and after injection of contrast medium. Precontrast T1-weighted and T2-weighted images were obtained with a 1.5-T MR imager. T1-weighted images were acquired 5, 15, and 30 min after gadodiamide injection (0.2 mmol/kg) and T1-weighted images with fat saturation were acquired 10 min after gadodiamide injection. RESULTS: Gadodiamide injection significantly increased signal intensity of normal (34 +/- %) and infarcted (90 +/- %) myocardium compared with their signal intensities on precontrast T1 weighted images. The contrast ratio was significantly increased, and the augmented ratios persisted throughout the 45-min observation period. The contrast ratio on T2-weighted images was comparable to that on contrast-enhanced T1 weighted images (with or without the use of fat saturation). However, the signal to-noise and contrast-to-noise ratios of T2-weighted images were significantly lower than those of contrast-enhanced T1-weighted images. The maximum contrast-to noise ratio for visualizing myocardial infarction was achieved on contrast enhanced T1-weighted images with fat saturation. CONCLUSION: Improved and persistent contrast between infarcted and normal myocardium can be produced on MR images by injecting gadodiamide at a dose of 0.2 mmol/kg, which provides prolonged delineation of myocardial infarctions. Maximum contrast-to-noise ratios for detecting myocardial infarction can be produced by using fat-saturated T1 weighted imaging after a high dose of this nonionic contrast medium has been administered. PMID- 8470612 TI - Aortic valve pressure gradients in patients with aortic valve stenosis: quantification with velocity-encoded cine MR imaging. AB - OBJECTIVE: Pressure gradients across the aortic valve due to stenosis of the valve must be measured accurately to evaluate the functional severity of the stenosis. Velocity-encoded cine MR has been used to quantify blood flow and flow direction and, more recently, the regurgitant fraction in aortic regurgitation. The purpose of this study was to determine the feasibility and accuracy of velocity-encoded cine MR for estimating pressure gradients across the aortic valve in patients with aortic stenosis. SUBJECTS AND METHODS: We used velocity encoded cine MR to measure flow velocity and determine pressure gradients across the aortic valve in 19 subjects. The pressure gradient (delta P) was estimated from the simplified Bernoulli equation by using the maximum instantaneous aortic jet velocity (Vmax): delta P (mm Hg) = 4V2max (m/sec). RESULTS: Maximum and mean systolic pressure gradients determined by using velocity-encoded cine MR were 3 148 mm Hg and 2-87 mm Hg, respectively, for all subjects. The pressure gradients correlated closely with gradients determined by using established methods: Doppler echocardiography and cardiac catheterization. Correlation coefficients (r) were .96 (y = 0.94x - 1.9) and .97 (y = 0.97x + 0.5), respectively. CONCLUSION: We conclude that velocity-encoded cine MR imaging provides a noninvasive and accurate means for quantifying the severity of valvular aortic stenosis. MR is a feasible method for determining pressure gradients across the aortic valve. PMID- 8470613 TI - Determination of cardiac ejection fraction and left ventricular volume: contrast enhanced ultrafast cine MR imaging vs IV digital subtraction ventriculography. AB - OBJECTIVE: To assess the accuracy of contrast-enhanced, single breath-hold cine MR imaging in the calculation of left ventricular volume and ejection fraction, we compared values obtained by using this method with those obtained by using IV digital subtraction angiography (IV-DSA). SUBJECTS AND METHODS: All patients (n = 28) had conventional cine and contrast-enhanced ultrafast cine MR imaging. For ultrafast cine MR imaging, a phase-rewind gradient-echo (rewind-SMASH) sequence was used: TR, 8 msec (standard excitation and acquisition block of 6 msec with phase rewind pulse of 2 msec); TE, 3.2 msec; a 128 x 96 matrix (pile encode factor, 6; k-space segment, 16); a 200-mm field of view; and one excitation. RESULTS: Values for left ventricular volume and ejection fraction obtained with ultrafast cine MR imaging correlated well with those obtained with IV-DSA (end diastolic volume, y = 0.986x - 7.79, r = .985; end-systolic volume, y = 0.863x + 0.71, r = .984; ejection fraction, y = 0.877x + 6.44, r = .887). In the calculation of left ventricular volume by the area-length method, manual tracing of the left ventricular cavity was more difficult when the conventional cine method was used than when the enhanced ultrafast cine method was used. CONCLUSION: Our results show that cardiac multiphase study with horizontal long axis, first-pass, contrast-enhanced, single breath-hold, cine MR imaging is an accurate and highly reproducible method of evaluating left ventricular volume and ejection fraction. PMID- 8470614 TI - Chest radiographic and CT findings after laser-assisted thoracic surgery. AB - OBJECTIVE: Laser-assisted thoracic surgery (performed through a thoracotomy or as an endoscopic procedure with thoracoscopy [pleural endoscopy]) is being used increasingly for lung-sparing resections of neoplasms, biopsies, and ablation of bullae. The technique is useful in treating patients who have limited pulmonary reserve and may avoid the problem of distortion of surrounding pulmonary tissue. Because laser energy causes injury to lung tissue, postoperative radiographs may show findings unique to the laser-assisted technique. The objective of this study was to determine postoperative radiographic findings common to laser-assisted surgery. MATERIALS AND METHODS: Pre- and postoperative and all follow-up chest radiographs were reviewed for 52 consecutive patients who had 60 laser-assisted thoracic surgical procedures (35 with an open thoracotomy, 25 with thoracoscopy) for resection of peripheral nodules (40), biopsy of focal (five) or diffuse (four) lung disease, or ablation of bullae (three). Postoperative chest CT studies available for 20 patients also were reviewed. All postoperative radiographic studies were evaluated for the presence and duration of pneumothoraces, pleural effusions, areas of parenchymal opacification or cavitation, and complications requiring surgical or radiologic intervention. RESULTS: Pneumothoraces and pleural effusions were seen in 88% and 83% of cases, respectively, and were typically small, uncomplicated, and of limited duration. Nonspecific parenchymal opacification of various degrees was observed at the operative site in all cases and usually regressed within days or weeks to areas of parenchymal scarring. Parenchymal cavitation at the operative site occurred in 15 patients (29%). Eight patients (15%) had complications that required intervention, primarily prolonged air leaks and pleural space complications. CONCLUSION: Radiographic findings after laser-assisted thoracic surgery are often nonspecific and of limited duration. In an asymptomatic patient, cavitation at the operative site is a normal finding related to the surgical technique and should not be misdiagnosed as infection or tumor. Radiographic findings normally resolve to stable cavitary or linear scars. PMID- 8470615 TI - Quality improvement techniques: value to improve the timeliness of preoperative chest radiographic reports. AB - OBJECTIVE: Continuous quality improvement is being advocated as a process that, if adopted, could lead to greater efficiency and productivity in medical institutions. To determine whether continuous quality improvement techniques could be effective in radiology departments, we undertook a model project that sought to improve our ability to interpret preoperative chest radiographs before surgery. All the preoperative films had been ordered by internists who determined, after seeing the patient, that the radiographic examination was warranted. MATERIALS AND METHODS: An eight-member team consisting of all persons involved in obtaining and interpreting preoperative chest radiographs was empowered to evaluate the existing process and make appropriate changes. Techniques used included studying and plotting the process, collecting data on the causes of delay, and basic statistical analysis of the data using histograms, Pareto diagrams, and control charts. On the basis of the data analysis, the team instituted changes, which included identifying the preoperative cards with a small flag, placing the processed films in yellow-colored jackets, and collating these jacketed films after their interpretation. RESULTS: After continuous quality improvement intervention, when the process for obtaining and interpreting preoperative radiographs was modified, the percentage of chest radiographs interpreted before surgery improved from approximately 83% to 98% (p < .001). The average waiting period between patient check-in at the outpatient reception area and interpretation of the preoperative chest radiograph was reduced from 275 to 77 min, a 72% reduction (p < .0302). CONCLUSION: Adoption of the quality improvement techniques of analyzing customer-supplier relations, understanding the causes of variation, and using data to solve problems appears to be a desirable management option that should be considered by all medical institutions interested in maximizing the quality of care offered while concurrently minimizing its cost. PMID- 8470616 TI - Screening for colon cancer: programs of the American College of Radiology. PMID- 8470617 TI - Consultants listing--January 1993. PMID- 8470618 TI - A comparison of controlled negative pressure and aerosol quantitative respirator fit test systems by using human subjects. AB - A quantitative respirator fit test system based on controlled negative pressure was evaluated by comparison testing with a computerized aerosol fit test system. Experiments ranged from multiple sequential tests of a single subject wearing a respirator equipped with a series of fixed leaks to sequential fit tests of 125 U.S. Air Force personnel using both systems. Throughout each test phase, measured negative pressure fit factors were consistently more conservative and less variable than aerosol fit factors. Comparison of subject and fixed leak fit factors indicated significant loss of aerosol during subject fit tests. Negative pressure system results did not show any effect from subject-related losses. PMID- 8470619 TI - Managing workplace exposure information. AB - A quality industrial hygiene program must include the collection and management of workplace exposure information. For many industrial hygienists, however, exposure monitoring data are the only exposure information available. Often, there is no attempt to qualitatively estimate and document all known exposures because mechanisms for doing so are not widely available. Industrial hygienists and other occupational health professionals generally lack information that provides sufficient knowledge and understanding about most employee exposures. The subject of this paper is a description of one company's approach to collecting and managing exposure information through a Job Exposure Profile (JEP) system. The JEP system provides a concise and detailed summary of exposure information for defined exposure groups that can be tracked over time. The value of the system lies in its simplicity and versatility, both as a dynamic tool to be incorporated into a comprehensive occupational health program and as a historical document. The system serves as an effective method for identifying and focusing on significant health hazards for each job at a facility from industrial hygiene, medical, epidemiologic, and engineering perspectives. PMID- 8470620 TI - Leakage of latex and vinyl exam gloves in high and low risk clinical settings. AB - The purpose of this study was to compare leakage rates of used latex and vinyl examination gloves from high and low risk clinical units. A total of 4838 latex and 1008 vinyl examination gloves were collected and tested by the Food and Drug Administration (FDA) watertight leak test: three brands of latex [Brand A: n = 2920; Brand B: n = 284; Brand C: n = 1634; and one brand of vinyl gloves (Brand D: n = 1008]. Seventy percent of latex gloves and 46.7% of vinyl gloves were collected from the high risk units. In general, there were no significant differences in leakage rates for vinyl gloves between high and low risk units. However, latex gloves leaked significantly more often at stress levels 2 and 3 from the high risk units as compared to the low risk units (X2 = 24.6, p < .0001). Regardless of level of stress and duration worn, 85.3% (860/1008) of used vinyl gloves and 18.4% (891/4838) of used latex gloves leaked, p < .001). There were significant differences in leakage rates between the three brands of latex gloves (Brand A, 9.8%; Brand B, 25.1%; Brand C, 30.9%, p < .001). Although latex gloves leaked slightly more frequently as stress level increased, glove material (latex or vinyl) and brand of glove were the most important predictors of leakage. PMID- 8470621 TI - Methylene chloride exposure in industrial workers. AB - Methods of environmental and biological monitoring were applied in order to evaluate exposure to methylene chloride in workers operating in a factory where this substance was used as a solvent. For the measurement of methylene chloride in environmental concentration, the ambient air was sampled by using personal passive dosimeters. The activated charcoal was desorbed with CS2 and injected into a gas chromatograph connected with a mass spectrometer. The biological monitoring of exposed workers was performed by determining the concentration of CO in alveolar air (CA, ppm) and methylene chloride in urine (Cu, mu/L). Immediately after the end of the exposure, a urine sample was collected avoiding solvent loss and using gas-tight samplers. Excretion level in urine was determined by using headspace gas chromatography linked to a mass spectrometer. The CO was determined at the end of the shift by using a portable instrument. A group of 20 workers (12 smokers and 8 nonsmokers) in the manufacturing plant were monitored. No significant correlation was observed among the CO of all subjects and the concentration of methylene chloride in ambient air. When those workers who smoked were removed from the analysis, a correlation between the methylene chloride concentration in air and the CO concentration in alveolar air was found. Significant linear correlation was found between the environmental concentration of methylene chloride in the breathing zone and methylene chloride concentration in urine. PMID- 8470622 TI - An analytical approach for reducing workplace health hazards through substitution. AB - Substitution for a harmful chemical implies that the desired function is maintained without using the harmful chemical in question. Improvement can be achieved if a less harmful chemical can be used or the same function obtained by changing the process and eliminating the harmful chemical agent. In 1982, Denmark introduced an authority regulation requiring substitution if functional and economical alternatives exist. This paper summarizes the results of 162 examples of substitution investigated by the Danish Occupational Health Services. The identification and implementation of substitution alternatives is described as an iterative process with seven distinct steps. Several tools that are useful in evaluating alternatives are described, including Hansen solubility parameters and vapor hazard ratios. In addition to the technical issues surrounding substitution, this paper describes the social interactions necessary to include all affected individuals, along with those having the proper expertise in the decision-making process. The use of the described methods may result in a safer work-place by eliminating certain hazardous chemicals or practices that have historically been used in specific industries. PMID- 8470623 TI - pH and Hp--gastric acid secretion and Helicobacter pylori: implications for ulcer healing and eradication of the organism. PMID- 8470624 TI - The accuracy of endoscopic estimates: what is large? What is small? PMID- 8470625 TI - Erythromycin: a motilin agonist and gastrointestinal prokinetic agent. AB - Erythromycin, a commonly used antibiotic, has recently emerged as a potential gastrointestinal prokinetic agent. This follows a decade of research into the mechanism of well-recognized gastrointestinal side effects of erythromycin. Early investigations demonstrated that erythromycin increased gastrointestinal motility, and more recent studies suggest that it fortuitously binds to and stimulates the receptor for the gastrointestinal peptide motilin. From this work it appears that a new and powerful class of gastrointestinal prokinetic agents will evolve from erythromycin and its derivatives. The role of motilin in the genesis of the fasting and fed patterns of gastrointestinal motility is emerging through the study of these motilin agonists. PMID- 8470626 TI - Omeprazole plus amoxicillin: efficacy of various treatment regimens to eradicate Helicobacter pylori. AB - In five subsequent open clinical studies, 180 patients with Helicobacter pylori (HP)-associated ulcer disease (n = 163) or severe functional dyspepsia (n = 17) requiring therapy were treated with either 40 mg omeprazole plus 4 x 500 mg amoxicillin suspension for 1 wk (group I, n = 35), 2 x 40 mg omeprazole plus 4 x 500 mg amoxicillin for 1 wk (group II, n = 50), 2 x 20 mg omeprazole plus 4 x 500 mg amoxicillin for 2 wk (group III, n = 62), 2 x 20 mg omeprazole (day 1-14) and 4 x 500 mg amoxicillin (day 8-14) (group IV, n = 22) or with 2 x 20 mg omeprazole for 2 wk (group V, n = 11). The HP eradication rates determined with a biopsy urease test, microscopy of a mucosal smear, specific culture, and histology after modified GIEMSA staining in the 5th wk after discontinuation of study medication were 61.3% in group I, 61.7% in group II, 82.8% in group III, 28.6% in group IV, and 0% in group V. Apart from clinical insignificant pharyngeal paresthesias (n = 6), nine patients (5.7%) with combined therapy complained of important side effects (stomatitis: n = 3, diarrhea: n = 3, allergic exanthema: n = 3) that led to termination of amoxicillin treatment in four cases (2.5%). We conclude that omeprazole-enhanced amoxicillin antibiosis is a simple and effective approach to the eradication of HP colonization. PMID- 8470627 TI - Are endoscopic measurements of colonic polyps reliable? AB - Many clinical studies of colorectal adenomatous polyps rely on endoscopic estimation of polyp size. To examine the reliability of such measurements, we conducted a study using artificial polyps in an endoscopy teaching model. Eight experienced endoscopists estimated the size of 13 polyps in two separate sessions 2 wk apart. Endoscopic estimates of polyp size tended to be significantly lower than the true polyp size for all polyps and all endoscopists at both sessions. We also found a statistically significant difference in the magnitude of the underestimation between the first and second session (p < 0.0001). At the first session, polyps tended to be estimated at 64% of their true size, and at the second session, the estimates tended to be at 77% of the actual polyp size. We estimate the magnitude of the variation in polyp measurements due to individual polyps, endoscopist, and examination session, and discuss the impact these sources of variation have in planning of clinical trials. PMID- 8470628 TI - Placement of a feeding button ("one-step button") as the initial procedure. AB - The procedure of choice for enteral feeding access is now percutaneous endoscopic gastrostomy (PEG). Standard PEG tubes have the disadvantages of clogging, stomal enlargement, and external bulkiness. Button replacement tubes can covert the more cumbersome PEG tubes to low external profile devices. A procedure and an early experience is described for placement of a button as a single-step procedure. This procedure is an over-the-wire, "push" procedure. Sixty-nine buttons were placed, 47 (61%) for neurologic reasons and 22 (32%) for cancer and other reasons. In 49 of the 69 (71%), there was no difficulty at all with insertion, and in only two (3%) could the button not be placed. Complications were assessed at 48 h and at 3 wk. No complications were found in 61 (90%). In only two patients (3%) were there serious complications (gastro-colon-cutaneous fistula and "peritonitis"). The One-Step Button represents a rapid, safe procedure for the placement of a low-profile PEG with its attendant advantages. PMID- 8470629 TI - Patient factors affecting Helicobacter pylori eradication with triple therapy. AB - Duodenal ulcer recurrence and gastritis are reduced with successful Helicobacter pylori treatment. To identify the patient factor influencing H. pylori eradication, we prospectively evaluated 96 consecutive patients undergoing a single 2-wk course of bismuth, tetracycline, and metronidazole therapy. At the time of initial esophagogastroduodenoscopy with biopsies, each patient had a profile obtained which included demographic information, gastrointestinal pathology, and H. pylori status of the spouse. Elimination of H. pylori was confirmed by repeat esophagogastroduodenoscopy with biopsies 4 wk after the completion of therapy and serial urea breath tests. Eradication at 4 wk was successful in 80 of 96 (83%) patients. On multivariate analysis, H. pylori elimination was associated with advanced age (p = 0.002) and a greater amount of chronic inflammation on baseline antral biopsy (p = 0.024). Eradication was inversely associated with the presence of a gastric ulcer (p = 0.008) and lack of medication compliance (p = 0.030). Successful eradication reduced the severity of both acute and chronic antral mucosal inflammation. Household income, gender, ethnic group, smoking, alcohol intake, and H. pylori status of the spouse did not differ between the eradicated and noneradicated groups. We conclude that it will be important to control for influential patient factors in future studies of H. pylori treatment regimens. PMID- 8470630 TI - Esophagitis and Helicobacter pylori in children: incidence and therapeutic implications. AB - The relationship between gastric Helicobacter pylori colonization and esophagitis was determined in 457 children undergoing endoscopic evaluation of abdominal pain and/or vomiting. In all patients, biopsies of the esophagus were examined histologically, and two antral biopsies were analyzed for the presence of H. pylori, using standard microbiological and histochemical techniques. The incidence of biopsy-proven esophagitis was similar in H. pylori-positive (15/56 patients) and -negative (94/401; p = NS) groups. Clinical improvement, after 2 months of antisecretory therapy with H2-receptor antagonists, was independent of H. pylori status (11/15 vs. 68/94 responders; p = NS). All 26 H. pylori-negative nonresponders became asymptomatic with a second course of H2-blockers. The 4/15 H. pylori-positive patients (all of whom had associated gastritis/duodenitis) who failed antisecretory therapy responded clinically to treatment with amoxicillin plus bismuth subsalicylate. These data indicate that primary treatment of biopsy confirmed esophagitis in children should include anti-secretory agents, regardless of H. pylori status. A small percentage of H. pylori-positive patients with esophagitis and concomitant gastroduodenal inflammation may require additional antibacterial therapy, suggesting that presence of the organism should be assessed in all pediatric patients undergoing upper endoscopic evaluation. PMID- 8470631 TI - Survival and prognostic factors of cirrhotic patients with ascites: a study of 134 outpatients. AB - Ascites is a complication of chronic liver disease that is associated with decreased survival. The purpose of the present study was to identify some prognostic factors easily obtainable by the clinician in a large group of cirrhotic patients with ascites, possibly useful for first screening of outpatients as candidates for liver transplantation. We studied 134 ambulatory patients with cirrhosis who came to our outpatient clinic between July 1983 and March 1989 because of an episode of ascites. These patients were then followed up for an average period of 31 +/- 23 months and survival was determined. Thirty-one variables determined at the time of inclusion were analyzed with a Cox proportional hazards model to identify predictors of mortality. Cumulative mortality as of June 30, 1991, was 59%. Factors independently correlated with death were: refractory ascites (relative risk, 4.78), low albumin levels (3.77), high Child-Pugh score (3.31), encephalopathy (2.71), high bilirubin levels (2.03), high gamma-glutamyl-transferase levels (1.87), and old age (1.57). The results show that 1) the occurrence of refractory ascites has a prognostic value superior to those of other variables, and 2) simple clinical and biochemical parameters, most of them components of the Child-Pugh score, are useful for a first screening of ascitic cirrhotic patients as candidates for liver transplantation. PMID- 8470632 TI - Ranitidine is effective therapy for erosive esophagitis. AB - Two ranitidine dosages were compared for the treatment of erosive esophagitis in a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Adults with endoscopically verified erosive esophagitis were treated with either ranitidine 150 mg four times daily (n = 106), ranitidine 300 mg four times daily (n = 106), or placebo (n = 116) for up to 12 wk. Patients were also encouraged to adhere to lifestyle modifications (e.g., to elevate the head of bed, etc). Erosive esophagitis healing, determined by endoscopy, was achieved in 69% and 62% of ranitidine-treated patients by 8 wk and in 79% and 74% by 12 wk (150 mg and 300 mg, respectively) compared with 28% of placebo-treated patients by 8 wk and 40% by 12 wk (p < 0.001 ranitidine vs. placebo). Onset of heartburn relief occurred within 24 h of initiating either ranitidine dosage, and relief was maintained throughout the 12-wk study. Both ranitidine dosages displayed safety profiles similar to that of placebo. We conclude that ranitidine 150 mg or 300 mg administered four times daily is effective for healing erosive esophagitis and relieving its symptoms. PMID- 8470633 TI - Correlation between esophageal motility and 24-hour pH recording in patients with gastroesophageal reflux. AB - The relationship between manometric and pH-metric data was studied in a group of 50 patients with symptoms of gastroesophageal reflux. Using a multiple regression analysis, we found that the total percentage of reflux was significantly correlated to the infradiaphragmatic length and resting pressure of the lower esophageal sphincter and also to the mean amplitude of the contractile waves of the distal esophagus, thus revealing the important role of these factors in the antireflux mechanism. When the patients were divided into groups according to their manometric characteristics and the values of the various pH-metric parameters between these groups compared using a one-way analysis of variance, we found that the amplitude of the contractile waves and the percentage of deglutitions without response were related not only to the total percentage of reflux but also to the number of reflux episodes of greater than 5 min duration and to the duration of the longest episode. This shows that prolonged exposure of the esophageal mucosa to the refluxed material may be due, in part, to an alteration in the capacity for esophageal clearing. PMID- 8470634 TI - Nifedipine for suspected type II sphincter of Oddi dyskinesia. AB - Endoscopic sphincterotomy may be the treatment of choice in type I sphincter of Oddi dyskinesia, but in type II dyskinesia the results are controversial, the complication rate may be high, and technically endoscopic sphincterotomy is not always possible. Nifedipine has been observed to relax the sphincter of Oddi and to enhance biliary drainage, especially in patients suffering from sphincter of Oddi dyskinesia. Therefore, nifedipine (10 mg, three times a day) was compared with placebo in treating suspected type II sphincter of Oddi dyskinesia in 13 cholecystectomized patients in a 16-wk study period in a double-blind "cross over" manner. Daily, the patients completed a diary of the pains, need of pain medication, and headache. Clinical examinations and blood tests for liver chemistry were performed at 4-wk intervals. Nifedipine diminished the number of days on which the patients experienced biliary-type pains (10.5 +/- 8.6 vs. 5.8 +/- 4.1, p = 0.042), and the number of days when pain medication was needed was slightly reduced (5.2 +/- 3.9 vs. 3.6 +/- 3.2, p = 0.066). After the study, one patient preferred to undergo endoscopic sphincterotomy, eight patients preferred to continue with nifedipine, and four patients preferred analgesics only. Liver chemistry remained unchanged in this study. Also heart rate, blood pressure, and the number of days of headache were not different between the nifedipine and placebo periods. We conclude that nifedipine is well tolerated in patients with type II sphincter of Oddi dyskinesia, and nifedipine may be tried for reducing the number of painful days and need for analgesics in patients with this disorder. PMID- 8470635 TI - The usefulness of endoscopic retrograde cholangiopancreatography in infants and small children. AB - We performed endoscopic retrograde cholangiopancreatography (ERCP) on nine infants and small children over a period of 7 yr from 1985 to 1991. In three infants, diagnosis on admission was congenital biliary atresia or neonatal hepatitis. In one, congenital biliary atresia was diagnosed by ERCP. In the other six cases, diagnosis on admission was congenital biliary dilation, acute cholangitis, or acute pancreatitis. In five, we diagnosed the anomalous arrangement of the pancreaticobiliary ductal system by ERCP. ERCP is a relatively easy and safe technique when applied to infants and small children. It is also a useful procedure when making morphologic diagnosis of organic disorders around the biliary and pancreatic ductal system, such as biliary atresia, intrahepatic cholestasis, and the anomalous arrangement of the pancreaticobiliary ductal system. It enables us to determine the surgical procedure and to investigate the residual bile duct after surgical treatment. Therefore, ERCP should be conducted on infants and small children who may be suffering from disorders of the pancreaticobiliary system. PMID- 8470636 TI - A study of the frequency of recovery of unexpected Giardia lamblia and Cryptosporidium from duodenal aspirates taken during routine upper endoscopy. AB - In this study, our objective was to determine whether the microscopic examination of duodenal aspirates recovered during routine upper endoscopy in unselected, immunocompetent patients, would disclose unsuspected Giardia lamblia or Cryptosporidium. DESIGN: Prospective, cross-sectional study to determine the prevalence of duodenal parasitosis. SETTING: Endoscopy unit in a university hospital. PATIENTS: One hundred and thirty-one unselected, immunocompetent patients undergoing upper endoscopy. MEASUREMENTS: Microscopic examination of duodenal aspirates, obtained during upper endoscopy. No pathogenic or commensal parasite was identified in any patient. CONCLUSIONS: No case of unsuspected parasitosis was found in the present study. On the basis of our findings, we do not recommend routine collection of duodenal aspirates during upper endoscopy. PMID- 8470637 TI - Endoscopic ultrasonography for assessing the horizontal extent of invasive gastric carcinoma. AB - Accurately determining the surgical resection line is essential for improving the prognosis of patients with gastric carcinoma. Endoscopic ultrasonography (EUS) was used to assess the horizontal extent of cancerous invasion below the mucosal layer. In 105 patients (110 lesions) with gastric carcinoma, ultrasonographic images of resected specimens were compared with histological findings. The horizontal extent of the hypoechoic region of in vitro ultrasound was compared with the horizontal extent of the cancerous invasion and fibrosis in histological sections. In cases showing echo patterns characteristic of peptic ulcerations within the tumor focus, the horizontal spread of the echo-poor region correlated well with the spread of fibrosis, but not with the cancerous lesion. In other cases with no ulceration, the horizontal spread of the echo-poor region corresponded well with the cancerous lesions. To evaluate oral invasion of the cancerous lesion below the mucosa, 16 patients with gastric carcinoma who had clips placed during endoscopy were subsequently examined by EUS. The use of EUS combined with the clips allowed for a more accurate diagnosis of the invasion, not only in the mucosa, but also into the submucosa and beyond. This combined diagnostic method was safe and useful for determining a suitable surgical resection line. PMID- 8470638 TI - Ultrasonographic prediction of esophageal varices in Schistosomiasis mansoni. AB - Bleeding from esophageal varices is a common and serious problem in Schistosomiasis mansoni. A simple and accurate method of detection would facilitate measurement of individual and community morbidity and allow institution of preventive measures. An ultrasonographic scoring system grading periportal fibrosis, portal vein diameter, spleen size, and portasystemic anastomoses was evaluated as a predictor of esophageal varices and a past history of upper gastrointestinal hemorrhage in 43 patients with hepatosplenic schistosomiasis. Ultrasonographic variceal score correlated (r = 0.86, p < 0.001) with the endoscopic variceal grade. Patients with a sonographic score of 5 or greater were highly likely (21 of 23) to have varices of grade II or greater (sensitivity, 91.3%; specificity, 94.7%). Only those with sonographic scores of 5 or greater (15 of 23) had bled from esophageal varices. The ultrasonographic score provided a simple, inexpensive, accurate, and noninvasive means of screening individuals with hepatosplenic schistosomiasis for esophageal varices, and correlated strongly with prior gastrointestinal hemorrhage. It is not known whether a similar score would be useful in hepatic cirrhosis. PMID- 8470639 TI - Initial experience with the Pentax VSB-P2900 enteroscope. AB - Pentax has introduced the VSB-P2900 for endoscopic evaluation of the small bowel. This is a standard video upper endoscope lengthened to 250 cm. We report a case utilizing this instrument. A 65-yr-old white male was admitted with respiratory failure. Gastrointestinal bleeding developed. Upper endoscopy, colonoscopy, push enteroscopy, and mesenteric angiography were nondiagnostic. Enteroscopy to the proximal to mid ileum was performed. Approximately 90% of the intubated small bowel mucosa was visualized. An arteriovenous malformation and an ulcer were identified and cauterized. Time elapsed from intubation to extubation was 90 min, including two KUBs. No further bleeding was observed. The VSB-P2900 is likely to simplify examination of the small intestine. Tip control allows a large percentage of the intubated small bowel to be visualized. A working channel allows therapeutics. The technique is simple, fast, and within the skills of most endoscopists. A safety and efficacy profile need to be determined. PMID- 8470640 TI - Pneumocystis carinii pneumonia in patients with ulcerative colitis treated with corticosteroids. AB - Today, Pneumocystis carinii pneumonia (PCP) is typically associated with AIDS. However, in the pre-AIDS era, PCP was known to be associated with various immunodeficiency states, malignancies, and immunosuppressive therapy, particularly the use of corticosteroids. PCP has been reported to occur during immuno-suppressive therapy of some chronic inflammatory states, but it has never been reported in patients with inflammatory bowel disease. We report two patients with ulcerative colitis who developed PCP during high-dose corticosteroid therapy, and review the literature regarding non-AIDS PCP. PCP should thus be added to the list of bronchopulmonary complications in inflammatory bowel disease. This report should give gastroenterologists further impetus to limit immunosuppressive therapy to its minimal effective dose. PMID- 8470641 TI - Gastrointestinal manifestations of amyloidosis: a case of diverticular perforation. AB - Amyloidosis is an intriguing disorder. Its clinical presentation usually rests on the organ(s) infiltrated with the amyloid. We report a patient who presented with peritonitis secondary to a perforated large jejunal diverticulum and multiple small bowel diverticula. We believe the diverticula were a direct result of primary amyloid infiltration of the intestine in the antimesenteric location. This is the first reported case of small bowel diverticula caused by amyloidosis. PMID- 8470642 TI - Crohn's disease and pancreatitis. AB - Pancreatitis has rarely been reported as a complication of Crohn's disease. We report our experience with two cases of pancreatitis associated with Crohn's disease. In one, the pancreatitis occurred secondary to duodenal Crohn's disease involving the ampulla of Vater. Endoscopic retrograde pancreatography demonstrated involvement of the ampulla, with marked dilation and delayed drainage of the pancreatic duct, suggesting mechanical obstruction. In the second patient, Crohn's disease was localized to the ileum and colon. We conclude that duodenal Crohn's can cause pancreatitis, and this may, in some cases, be on an obstructive basis. In addition, non-duodenal Crohn's disease can be associated with pancreatitis as well. In a patient with a history of Crohn's disease presenting with an atypical exacerbation, pancreatitis should be considered. PMID- 8470643 TI - Tracheoesophageal fistula complicating herpes esophagitis in AIDS. AB - Immunocompromised individuals are susceptible to a variety of esophageal infections. Organisms responsible for esophagitis in patients with the acquired immunodeficiency syndrome (AIDS) are briefly reviewed. Usually confined to the esophageal mucosa, pathogens known to have the potential for transmural invasion are identified. The first report of tracheoesophageal fistulization in an AIDS patient with herpes esophagitis is presented. PMID- 8470644 TI - Acetaminophen hepatotoxicity: potentiation by isoniazid. AB - Potentiation of acetaminophen hepatotoxicity has previously been associated with a history of alcohol abuse. Presented here is the case of a 21-yr-old Philippino female with rapidly deteriorating hepatic functions. She had been on isoniazid, 300 mg daily, as prophylaxis against tuberculosis due to a positive tuberculin skin test. She took 3.25 g of acetaminophen for abdominal cramping and subsequently had rapid deterioration of liver function manifested by prolongation of the prothrombin time, elevated ammonia, marked elevation of transaminases, and hyperbilirubinemia. Over the course of 1 wk, these values essentially normalized and she was discharged. Isoniazid induces the cytochrome P-450 system, resulting in increased metabolism of acetaminophen, formation of toxic metabolites, depletion of glutathione stores, and subsequent hepatocellular injury. Patients on isoniazid should use caution when taking acetaminophen since the potentially hepatotoxic effects may be amplified due to induction of the cytochrome P-450 system. PMID- 8470645 TI - Endoscopic ultrasound in the morbidly obese patient: a new indication. PMID- 8470646 TI - Primary biliary cystic tumors of the liver. AB - Five cases of primary cystic tumors of the intrahepatic bile duct are documented over a 5-yr period. Clinically, two cases had recurrent episodes and one had a first attack of jaundice, fever, and pain in the upper abdomen; one complained of abdominal fullness and one was asymptomatic. The appearance of the tumors were single, large, multilocular, and cystic. Important radiological findings included irregular thickness of the cystic wall, internal septation, and papillary projection. Marked biliary dilation was demonstrated in four of the patients. On the cholangiogram, amorphous filling defects were seen in the dilated extrahepatic bile ducts, and mucinous material could be removed from the ducts as well. Obstruction of the bile ducts by this mucinous bile was assumed to be the cause of cholangitis in three patients. Histological examination revealed three cases of cystadenoma and two cases of cystadenocarcinoma. PMID- 8470647 TI - Intestinal perforation due to Mycobacterium tuberculosis in HIV-infected individuals: report of two cases. AB - Intestinal perforation is an extremely uncommon complication of Mycobacterium tuberculosis (MTB) infection. We describe two cases of multiple intestinal perforations secondary to MTB in individuals infected with the human immunodeficiency virus (HIV) presenting at the Los Angeles County-University of Southern California Medical Center over a 2-month period. For each case, this was the first presentation of AIDS. One of the two patients had concurrent pulmonary involvement. One patient died, and the other responded to therapy and was discharged in stable condition. The most striking finding in both cases was the extremely large number of acid-fast bacteria seen transmurally on the pathological specimens. This might be related to impaired T-cell function. The resurgence of MTB infection in North America, in the presence of the AIDS epidemic, may result in an increasing frequency of unusual presentations, such as intestinal perforation. Intestinal perforation due to MTB should be considered in HIV-infected patients presenting with an acute abdomen. PMID- 8470648 TI - Bile acids for PSC: promise for the future or placebo for the present? PMID- 8470649 TI - Balloon dilation versus Eder-Puestow: bigger and better? PMID- 8470650 TI - Variceal heavyweights: the ring versus the needle. PMID- 8470651 TI - Helicobacter pylori does not increase gastrin in chronic gastritis. PMID- 8470652 TI - Clofazimine-induced eosinophilic gastroenteritis in AIDS. PMID- 8470653 TI - Intramural gastric hematoma originating from an atherosclerotic aneurysm of a gastric artery. PMID- 8470654 TI - The incidence of bactibilia in gallstone patients without evidence of chronic or acute cholecystitis. PMID- 8470655 TI - Peritonitis with Mycobacterium avium in a patient with hepatic cirrhosis. PMID- 8470656 TI - An open trial of Cedemin, a Gingko biloba extract with PAF-antagonistic effects for ulcerative colitis. PMID- 8470657 TI - Diffuse cerebral edema following endoscopy. PMID- 8470658 TI - Ultrasonic diagnosis of adult intussusception. PMID- 8470659 TI - Long accessory hepatic duct associated with congenital dilation of the common bile duct. PMID- 8470660 TI - Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) and its determinants: a cohort study in Kigali, Rwanda. AB - The authors report the results of the first 2 years of follow-up of a prospective cohort study on the mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) and its determinants which started in November 1988 in Kigali, Rwanda. The study sample consists of 218 newborns of 215 HIV-1 seropositive women matched to 218 newborns of 216 HIV-1 seronegative women of the same age and parity. They were followed every 2 weeks during the first 2 years of follow-up. HIV-1 antibodies were detected by enzyme-linked immunoadsorbent assay and Western blot at 3-month intervals. Two methods of calculating the mother-to-child transmission rate were used: method 1 combines the information provided by the persistence of HIV-1 antibodies at 15 months of age in children born to HIV seropositive mothers and the excess mortality in this group compared with the cohort of children born to HIV seronegative mothers; method 2 is a case-by-case evaluation of all the children born to HIV seropositive mothers. A logistic regression model was used to study the determinants of transmission. The probability of survival at 24 months of age was 81% (95% confidence interval (CI) 75-86) in children born to seropositive mothers, compared with 95% (95% CI 92-98) in children born to seronegative mothers (p < 0.001). The mother-to-child transmission rate calculated with method 1 was 25.7% (95% CI 18.8-32.5). With method 2, the medium estimate was 24.7%. In the multivariate analysis, a CD4/CD8 ratio < 0.5 was the only maternal factor statistically associated with an increased risk of mother-to-child transmission of HIV-1 (odds ratio = 2.9, 95% CI 1.2-7.2). The authors' findings present evidence for a higher mother-to-child transmission rate of HIV-1 in children born in Rwanda than in industrialized countries. PMID- 8470661 TI - Comparison of voluntary and blinded human immunodeficiency virus type 1 (HIV-1) seroprevalence surveys in a high prevalence sexually transmitted disease clinic population. AB - To compare the seroprevalence of and risk factors for human immunodeficiency virus infection (HIV) among patients attending a public sexually transmitted disease clinic, the authors conducted both voluntary and blinded seroprevalence surveys between June 1989 and August 1990. For the voluntary survey, every twenty fifth patient attending the clinic for a new problem was invited to receive anonymous testing for HIV antibody. For the blinded survey, sera obtained for syphilis serologies from 2,297 (86%) of the 2,682 patients attending the clinic for a new problem were tested for HIV antibody after all personal identifiers were removed. Of the 946 eligible patients, 631 (66.7%) agreed to participate in the voluntary survey. Black men were significantly less likely to participate than other men and women (p < 0.0001). The prevalence of HIV antibody was 25% greater in the blinded survey than in the voluntary survey (15.2% and 11.4%, respectively, p < 0.05). This difference was due primarily to black homosexual/bisexual men, who had a 12.7-fold greater risk of HIV infection in the blinded survey than in the voluntary survey. These results suggest that blinded seroprevalence surveys may provide a better prevalence estimate of HIV infection than voluntary surveys. The greater risk for HIV infection observed among homosexual and bisexual black men, who were tested only in the blinded serosurvey, suggests that efforts to increase voluntary testing for HIV infection in this group should be developed. PMID- 8470662 TI - Leukemia in telephone linemen. AB - This case-control study examines potential associations between telephone linework and the occurrence of leukemia except chronic lymphocytic leukemia in a primarily retired population of American Telephone and Telegraph Company (AT&T) workers. Cases died between 1975 and 1980. Exposure is defined both by job title and, for workers with complete job histories, by a lifetime exposure score based on industrial hygiene personal monitoring measurements of line and nonline jobs. When the time-weighted average mean for each job is accumulated into a lifetime exposure score, workers with scores above the median for the population show an excess of leukemia 2.5 times higher than workers below the median (95% confidence interval (CI) 0.7-8.6). Those individuals with long duration of employment in jobs with intermittent peak exposures may be at higher risk of leukemia than those with a constant exposure level. Analyses that allow for a latent period suggest the risk is associated with exposures that occurred 10 or more years before death. Workers with peak exposure scores above the median have odds ratios of 2.4 (95% CI 0.7-9.0) and 6.6 (95% CI 0.7-58) for latent periods of 10 and 15 years, respectively. The data suggest an increasing risk with increasing exposure (p for trend = 0.05) when cumulated scores are based on peak exposure scores. Peak exposures tended to occur in cable splicing work and in old telephone switching offices. The numbers in this study are small and observed differences may be due to chance. PMID- 8470663 TI - Parental smoking and risk of childhood brain tumors. AB - Data from a large, population-based, case-control study were analyzed to assess the role of parental smoking in childhood brain tumors. Parents of 361 cases, newly diagnosed between January 1, 1977 and December 31, 1981 and ascertained from eight Surveillance, Epidemiology, and End Results (SEER) program registries, and 1,083 controls had been interviewed. No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for < 1 pack/day and 1.0 for > or = 1 pack/day for mothers, and 0.68 for < 1 pack/day and 1.07 for > or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for < 1 pack/day and 1.01 for > or = 1 pack/day for mothers, and 0.90 for < 1 pack/day and 1.15 for > or = 1 pack/day for fathers). Mothers were also specifically asked if they smoked during the pregnancy, and no association was found compared with never smokers (OR = 1.08, 95% confidence interval (CI) 0.80-1.45) or for ever-smokers who continued to smoke during pregnancy compared with those who stopped smoking during pregnancy (OR = 1.15, 95% CI 0.75-1.78). Finally, no significant increase in risk of brain tumors was found for the child's passive exposure to parental smoking during the period from birth to diagnosis of the brain tumor in the case. The lack of an effect of parental smoking was observed for both the major histologic types and locations of brain tumors. These findings and those from earlier studies provide no support for the hypothesis that parental cigarette smoking influences the risk of brain tumors in children. PMID- 8470664 TI - Risk of childhood cancer for infants with birth defects. I. A record-linkage study, Atlanta, Georgia, 1968-1988. AB - To evaluate the risk of childhood cancer among infants with serious birth defects, the authors linked records of the population-based registry of the Georgia Center for Cancer Statistics for 1975 to 1988 with records of the population-based Metropolitan Atlanta Congenital Defects Program for 1968 to 1987. During the study period, birth defects were diagnosed in 19,373 infants younger than 1 year of age, and cancer was diagnosed in 400 children younger than 15 years of age. The observed number of children with a defect who developed cancer was compared with the number expected on the basis of the cancer registry rates. Of the 19,373 children with birth defects, 31 developed cancer (standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) 1.5-3.2). Two associations were found: of 532 children with Down's syndrome (trisomy 21), three developed acute leukemia (SIR = 50.8, 95% CI 10.5-148.5) while of 746 children with pyloric stenosis, four developed cancer (SIR = 7.5, 95% CI 2.0 19.3). These data show that children with selected birth defects are at increased risk for specific childhood cancers. Such record-linkage can reveal new associations, which can in turn help researchers understand underlying mechanisms common to teratogenesis and carcinogenesis. PMID- 8470665 TI - Risk of childhood cancer for infants with birth defects. II. A record-linkage study, Iowa, 1983-1989. AB - To attempt to confirm associations found in a companion study in Atlanta, Georgia between Down's syndrome and acute leukemia and between pyloric stenosis and childhood cancer, the authors used the State Health Registry of Iowa to link the records of infants and children with cancer for 1983 to 1989 with the records of infants with birth defects for 1983 to 1988. During the study period, birth defects were diagnosed in 10,891 infants younger than 1 year of age, and cancer was diagnosed in 396 children younger than 8 years of age. The authors compared the observed number of children with a defect who developed cancer with the number expected on the basis of the cancer registry rates. Of the 10,891 children with birth defects, 16 developed cancer (standardized incidence ratio (SIR) = 2.0, 95% confidence interval (CI) 1.2-3.3). Of 251 children with Down's syndrome (trisomy 21), two developed leukemia (SIR = 32.1, 95% CI 3.9-116.0). None of the infants with cancer had pyloric stenosis (SIR = 0.0, 95% CI 0.0-6.7). The results of this study supported the association found in the Atlanta study between Down's syndrome and leukemia, but did not support the association found there between pyloric stenosis and childhood cancer. This study, however, had a shorter follow up period and a smaller number of subjects than the Atlanta study. PMID- 8470666 TI - Blood pressure and industrial lead exposure. AB - The association between environmental lead exposure and raised blood pressure remains controversial. This association was examined in a cross-sectional study in 1981 on 809 male workers who were occupationally exposed to lead in a factory manufacturing car lead accumulator batteries in Birmingham, United Kingdom. Lead exposure was assessed by blood lead levels, blood zinc protoporphyrin levels, and years of industrial exposure to lead. The geometric mean blood lead level was 31.6 micrograms/dl with minimum and maximum values of 0 microgram/dl and 98 micrograms/dl, respectively. Unadjusted systolic blood pressure rose with increasing blood lead levels (analysis of variance, F = 3.3, p < 0.05) from 127 mmHg (95% confidence interval (CI) 123.5-130.5) in men with blood lead levels less than 21 micrograms/dl to 133 mmHg (95% CI 128.7-137.3) in men with levels exceeding 50 micrograms/dl. Following adjustment for the confounding effects of age, body mass index, and alcohol consumption, however, the effect of blood lead on systolic pressure was diminished (analysis of variance, F = 1.3, not significant) to 129 mmHg and 132 mmHg in the respective categories. There was no association between diastolic blood pressure and blood lead. Zinc protoporphyrin levels and years of industrial lead exposure did not raise adjusted systolic or diastolic pressure. In conclusion, subject to the limitations inherent in a cross sectional survey, the findings are consistent with a weak effect of industrial lead exposure on systolic blood pressure, within the range of exposures observed in this study. PMID- 8470667 TI - A comparison of prospective and retrospective responses on sudden infant death syndrome by case and control mothers. AB - Based on information from two studies of sudden infant death syndrome (SIDS) from 1988-1991 in Tasmania, Australia, prospective and retrospective maternal responses to an identical set of questions were compared for 27 cases and 25 controls. There was good agreement on demographic factors, maternal obstetric history, parental smoking, and infant feeding practices. Reported changes in sleep habits were slightly greater for cases, and further work is needed to determine if this reflects recall bias or real changes during early infant life. Case mother reports regarding family history of disease and infant bedding were more discrepant, suggesting recall bias and supporting prospective collection of this information. PMID- 8470668 TI - Representative and misrepresentative associations of birth defects in livebirths. Conditions under which relative risks greater than unity in livebirths necessarily imply relative risks greater than unity in all conceptuses. AB - One may express the relative risk of defect in all conceptuses, r(def), as a function of the relative risk of defect in livebirths, r(def,lb), and in embryonic and fetal deaths, r(def,efd), as r(def) = C(lb)r(def,lb) + C(efd)r(def,efd), where C(lb) and C(efd) are coefficients defined in terms of conceptus and defect viability and lethality. If the relative risk of birth defect in livebirths, r(def,lb), is greater than unity, but the relative risk of defect in all conceptuses, r(def), is equal to or less than unity (or the reverse pattern holds), then the relative risk of defects in livebirths may be said to be "distorting" or "misrepresentative" because it does not reflect the nature of the association in all conceptuses. The authors define and present an explicit expression for a boundary upon the relative risk of defect in livebirths. If the relative risk of defect in livebirths is (validly) greater than this boundary value, then the relative risk in all conceptuses must be greater than unity and the observed relative risk of defect in births is "representative" and not distorting. The authors show that the boundary value is equal to 1/C(lb), where C(lb) is a simple function of the lethality of all unexposed conceptuses, the lethality of unexposed conceptuses with defect, and the relative risk of any embryonic and fetal death. Tables of the boundary relative risk for various values of these variables are presented. Over a very wide range of reference variables, a (valid) relative risk of defect in livebirths of 3.5 or greater implies a positive association with defect in all (recognized) conceptuses in the population studied. PMID- 8470670 TI - FDA clears 26 new drugs for marketing in 1992. PMID- 8470669 TI - Sample size and power determination for a binary outcome and an ordinal exposure when logistic regression analysis is planned. AB - General methods of sample size determination for logistic regression analyses are now available, but these will often require substantial information for their application. The author presents methods useful in the special case of a binary outcome and a three-level quantitative exposure, which includes application to a three-level ordinal exposure for a specified scaling. The computationally simple methods were developed in planning an investigation of the prognostic value of multidrug resistance gene (mdr1) expression in sarcoma. Because logistic regression was planned for the analysis, calculations were based on the ability to detect a linear trend in the log odds of tumor response to chemotherapy associated with increases in the level of mdr1 expression from negative to low positive to high positive. Closed form expressions were used to assess sensitivity to the ordinal scaling and the distribution of the mdr1 levels, and to the assumption of a linear trend in the log odds versus a linear trend in the proportions. PMID- 8470671 TI - Radiopharmaceutical providers to continue growth. PMID- 8470672 TI - Annual Lilly survey shows hospital pharmacy purchases up nearly 20% in 1991. PMID- 8470673 TI - Increasing pharmacist involvement in cardiopulmonary resuscitation attempts. PMID- 8470674 TI - Showing your worth to the bosses. PMID- 8470675 TI - Possible incompatibilities with immune globulin for i.v. use. PMID- 8470676 TI - The value of pharmaceutical care. PMID- 8470677 TI - Promotion of cost-effective benzodiazepine sedation. PMID- 8470678 TI - Alternative way to deal with nonformulary drugs. PMID- 8470679 TI - New emphasis on home care. PMID- 8470680 TI - Appropriateness of antibiotic selection and use in laminectomy and microdiskectomy. AB - The selection and timing of antibiotic prophylaxis in spinal surgery patients were studied. All laminectomy and microdiskectomy cases in which surgical-wound infection had developed within 60 days of surgery during 1990 at a medical center were retrospectively reviewed because of the high rate of postoperative wound infection for these procedures at the institution. The evaluation covered drug selection, the timing of antibiotic administration relative to the surgical incision, culture and susceptibility test results, and the length of the surgical procedure. Surgical-wound infection was found to have developed in 22 (7%) of the 315 patients who underwent laminectomy or microdiskectomy. There was no apparent difference between the infected group and a matched, uninfected control group in either the antibiotic selected or the number of doses given. On the basis of the organisms isolated from the wounds and susceptibility test results, the selection of cefazolin as the antibiotic was appropriate in 17 of the 22 infected patients. However, compared with the control group, the infected group had a significantly higher percentage of patients in whom antibiotics had been given more than two hours before the time of the surgical incision. The policy on administering prophylactic antibiotics was modified; current guidelines include giving the first dose of cefazolin upon the induction of anesthesia and follow-up administration in three hours if the incision has not been closed by then. The selection of a prophylactic antibiotic for spinal surgery patients was appropriate, but the timing of drug administration was usually not optimal. PMID- 8470681 TI - Ondansetron use in a major university teaching hospital. AB - A drug-use evaluation of ondansetron was conducted. Literature-based criteria for the use of ondansetron were developed by an oncology specialty resident and a clinical pharmacy specialist in oncology. Orders for ondansetron written in the hospital or in the outpatient oncology clinic were reviewed over a nine-week period. After an interval of education, the use of ondansetron was re-evaluated. The data collected included the indication for use, dosage, route of administration, and, for inpatient orders during the first evaluation, therapeutic outcome. In the first evaluation, 100 orders were reviewed. Some 87% of the orders for inpatients and 80% of the outpatient orders met the criteria for therapeutic indication. Criteria for dosage and administration were met by 76% of the inpatient orders and 83% of the outpatient orders. The inpatient orders met the criteria for therapeutic outcome in 93% of cases. In the follow-up evaluation, 50 orders were reviewed. Some 96% of the inpatient orders and 100% of the outpatient orders met the criteria for therapeutic indication. Dosage and administration criteria were met by 92% of the inpatient orders but only 24% of the outpatient orders. A considerable potential for cost avoidance was identified. An evaluation of ondansetron use led to general improvements in prescribing patterns, but continued monitoring is necessary to reduce the use of inappropriate dosages and routes of administration for outpatients. PMID- 8470682 TI - Use of vitamin and mineral supplements by pharmacy students. AB - Use of vitamin and mineral supplements by undergraduate pharmacy students and the students' perceptions and beliefs about these products were studied. Undergraduate pharmacy students from two schools in Philadelphia completed a questionnaire in which they were asked whether they had taken vitamin or mineral supplements within the preceding two weeks, the reason for taking the supplements, and the identity of the type of products taken. General demographic information and a self-assessment of health and diet were also obtained. In addition, using a five-point Likert scale, students were asked to rate the degree to which they agreed with five controversial statements regarding vitamin and mineral supplements. Of the 692 students completing the questionnaire, 47% had taken supplements in the preceding two weeks. This percentage is higher than that determined in surveys of the general population and of professionals in other health disciplines. No significant difference was noted in the percentage of men and women who took supplements, but the types of products taken by men and women differed significantly. The most common reasons for taking supplements were inadequate diet, to improve energy, for stress, and for colds. Year in school had a modest influence on the beliefs about vitamin and mineral supplement use expressed by students. The use of vitamin and mineral supplements among pharmacy students was high. Pharmacy schools should devote time in the curriculum to the sociological and clinical aspects of vitamin and mineral therapy. PMID- 8470683 TI - Automated compounder for adding ingredients to parenteral nutrient base solutions. AB - The effects of using an automated compounder for adding ingredients to parenteral nutrient (PN) base solutions was evaluated. Work-sampling methods were used to determine the amount of time spent by pharmacists and technicians in the production of PN solutions before and after the implementation of an automated device for adding ingredients to PN base solutions. Costs of materials and supplies were evaluated before and after the PN compounder was implemented. Qualitative (sterility) and quantitative (accuracy) analyses were performed by the hospital laboratory. A personnel time savings of 5.4 minutes per PN solution (1.0 full-time equivalent [FTE]) was shown. There was also an additional 0.5 FTE saved in activities not directly related to PN production. There was a 1.5% increase in pharmacist time (mean +/- S.D. preimplementation, 12.66 +/- 2.33 minutes; postimplementation, 12.85 +/- 1.96 minutes) and a significant 27.9% decrease in technician time (mean +/- S.D. preimplementation, 20.29 +/- 2.47 minutes; postimplementation, 14.62 +/- 2.24 minutes) per PN solution. The break even point for personnel and supply costs was 33 PN solutions. Qualitative analysis resulted in one positive culture preimplementation and no positive cultures postimplementation. Quantitative analysis showed an improvement in compounding accuracy. The use of an automated compounder for adding ingredients to PN base solutions resulted in personnel time savings and improved accuracy. PMID- 8470684 TI - Stability of hydralazine hydrochloride syrup compounded from tablets. AB - The stability of hydralazine hydrochloride in an oral syrup and with various adjuvants that might be used in a liquid formulation was studied. A syrup containing triturated hydralazine hydrochloride 50-mg tablets, a maltitol-based syrup vehicle, and other additives was prepared; the theoretical initial concentration of hydralazine hydrochloride was 1.25 mg/mL. Three samples were each stored at 5, 40, 50, 60, and 70 degrees C. Drug concentration was measured with high-performance liquid chromatography at times ranging from 2 to 23 days. In a second study, five 50-mL solutions were prepared: (1) hydralazine 1% with no pH adjustment, (2) hydralazine 1% with pH adjusted to 6.33, (3) hydralazine 1% and edetate disodium 1% with no pH adjustment, (4) hydralazine 1% and edetate sodium 1% with no pH adjustment, and (5) hydralazine 1% and sodium bisulfite 1% with no pH adjustment. Drug concentration was determined after storage for one week at 50 degrees C. There was apparent first-order degradation of hydralazine hydrochloride at all temperatures. An Arrhenius plot was used to calculate a shelf life of the syrup of 5.13 days at 25 degrees C. There were no changes in pH or physical appearance. In the second study, hydralazine hydrochloride solution turned yellow immediately after edetate sodium [corrected] was added; at one week the loss of drug was 29%. Addition of sodium bisulfite caused a more intense yellow coloration, and loss of drug at one week was 80%. Changes in pH were minimal. An Arrhenius plot showed that hydralazine hydrochloride was relatively unstable in an oral syrup at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470685 TI - Compatibility of cyclosporine with fat emulsion. AB - The compatibility of cyclosporine with fat emulsion was studied. Admixtures consisted of cyclosporine injection at final drug concentrations of 0.5 and 2.0 mg/mL in 10% and 20% fat emulsion. Fat emulsion stability was determined by visual inspection, pH testing, and particle-size measurements at 0, 24, and 48 hours. Cyclosporine stability was measured with high-performance liquid chromatography at the same intervals. The admixtures were stored in glass containers at 23-25 degrees C under fluorescent light. Mean particle diameters remained relatively constant in all the admixtures throughout the study period. No particles larger than 6 microns were observed. Cyclosporine retained more than 96% of its initial concentration in all the admixtures. There were no changes in color or consistency, and pH did not vary by more than 0.11 pH unit. Cyclosporine 0.5 or 2 mg/mL was compatible with 10% or 20% fat emulsion at room temperature in glass containers for up to 48 hours. PMID- 8470686 TI - Stability of famotidine in an extemporaneously prepared oral liquid. AB - The stability of famotidine in an extemporaneously prepared oral liquid stored at 4 and 24 degrees C for 30 days was studied. Famotidine liquid was prepared by pulverizing and suspending 12 40-mg tablets in distilled water. This mixture was diluted with cherry syrup to a total volume of 60 mL, resulting in a famotidine concentration of 8 mg/mL. The liquid was divided into two 30-mL amber glass bottles and stored at 4 degrees C and at room temperature (24 degrees C). Samples from each of the two bottles were assayed for famotidine content by high performance liquid chromatography. Each sample was assayed in duplicate at time 0 and on days 2, 5, 10, 15, 20, 25 and 30. The concentration of famotidine remained above 90% of original concentration for 20 days at 4 degrees C and for 15 days at room temperature. After 30 days, famotidine concentration was reduced by 15% and 24% at 4 degrees C and room temperature respectively. Famotidine liquid 8 mg/mL compounded extemporaneously from tablets was stable for 20 days at 4 degrees C and for 15 days at 24 degrees C. PMID- 8470687 TI - Stability of procainamide hydrochloride syrups compounded from capsules. AB - The stability of procainamide hydrochloride in two oral syrups, one prepared with sucrose and the other with maltitol, was studied. A syrup containing powder from 500-mg procainamide hydrochloride capsules, simple sucrose syrup, and other additives was prepared; the theoretical initial concentration of procainamide hydrochloride was 50 mg/mL. Three samples each were stored at 40, 50, 60, and 70 degrees C. Drug concentration was measured with high-performance liquid chromatography at times ranging from 2 to 107 days. In a second study, a syrup containing powder from 500-mg procainamide hydrochloride capsules, a maltitol based syrup vehicle, and other additives was prepared; the theoretical initial drug concentration was 50 mg/mL. Three samples each were stored at 40, 50, 60, and 70 degrees C. Drug concentration was measured at times ranging from 7 to 187 days. For the sucrose-based syrup, there was apparent first-order degradation of procainamide hydrochloride at all temperatures. An Arrhenius plot was used to calculate a shelf life of the syrup of 456 days at 25 degrees C. Most samples turned brown over time, and pH values were constant. For the maltitol-based syrup, drug degradation appeared to be biphasic; an initial period during which concentrations remained at nearly 100% was followed by apparent first-order degradation. Arrhenius plotting gave a shelf life of 97 days at 25 degrees C. Most samples turned brown over time, and pHs remained constant. Arrhenius plots indicated that in a maltitol-based oral syrup, procainamide hydrochloride was more stable than in a sucrose-based syrup when the storage temperature was above 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470689 TI - Stability and compatibility of fluconazole and aminophylline in intravenous admixtures. AB - The stability of aminophylline and fluconazole in intravenous admixtures containing both drugs was studied. Admixtures containing aminophylline 2.0 or 1.0 mg/mL and fluconazole 1.5 or 0.5 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared. Each admixture was prepared in triplicate in glass containers and kept at 24 degrees C. Immediately after preparation and at one, two, and three hours, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and fluconazole concentration. More than 98% of the initial aminophylline and fluconazole concentrations remained at each test interval. There was no visible evidence of precipitation, gas formation, or color change. No appreciable change in pH occurred during the study period. Aminophylline 1.0 2.0 mg/mL and fluconazole 0.5-1.5 mg/mL admixed in 5% dextrose injection or 0.9% sodium chloride injection were stable and compatible for up to three hours at 24 degrees C. PMID- 8470688 TI - Stability and compatibility of minocycline hydrochloride and rifampin in intravenous solutions at various temperatures. AB - The stability and compatibility of minocycline hydrochloride and rifampin in intravenous solutions at several temperatures were studied. Triplicate test solutions of (1) minocycline hydrochloride 0.1 mg/mL or rifampin 0.1 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection and (2) minocycline hydrochloride 0.1 mg/mL admixed with rifampin 0.1 mg/mL in 0.9% sodium chloride injection were prepared and stored at various temperatures. Samples were removed at intervals for up to seven days and stored at -70 degrees C until analyzed. Drug concentration was measured by stability-indicating high-performance liquid chromatography. Compatibility was assessed by visual and turbidimetric examination. For the solutions containing the drugs separately, minocycline hydrochloride was stable in both diluents, with the initial concentration declining by 8% at 24 degrees C and 2% at 4 degrees C over seven days. Rifampin was less stable, losing 6-8% of the initial concentration in three days at 4 degrees C and 5-7% in 8 hours and 13-17% in 24 hours at 24 degrees C. There was no change in turbidity in the solutions containing either minocycline hydrochloride or rifampin. The admixture, however, was turbid after 72 hours at 37 degrees C. Minocycline hydrochloride in the admixture was stable for seven days at 24 and 4 degrees C but not for three days at 37 degrees C. The concentration of rifampin decreased 20% in one day at 24 degrees C, 8-10% in three days at 4 degrees C, and 14% in 4 hours and 40% and in 24 hours at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470690 TI - Trends in computer hardware and software. AB - Previously identified and current trends in the development of computer systems and in the use of computers for health care applications are reviewed. Trends identified in a 1982 article were increasing miniaturization and archival ability, increasing software costs, increasing software independence, user empowerment through new software technologies, shorter computer-system life cycles, and more rapid development and support of pharmaceutical services. Most of these trends continue today. Current trends in hardware and software include the increasing use of reduced instruction-set computing, migration to the UNIX operating system, the development of large software libraries, microprocessor based smart terminals that allow remote validation of data, speech synthesis and recognition, application generators, fourth-generation languages, computer-aided software engineering, object-oriented technologies, and artificial intelligence. Current trends specific to pharmacy and hospitals are the withdrawal of vendors of hospital information systems from the pharmacy market, improved linkage of information systems within hospitals, and increased regulation by government. The computer industry and its products continue to undergo dynamic change. Software development continues to lag behind hardware, and its high cost is offsetting the savings provided by hardware. PMID- 8470691 TI - Adverse drug reaction surveillance in an emergency room. PMID- 8470692 TI - Stability of bupivacaine hydrochloride, epinephrine hydrochloride, and fentanyl citrate in portable infusion-pump reservoirs. PMID- 8470693 TI - Visual compatibility of ciprofloxacin with selected components of total parenteral nutrient solutions during simulated Y-site injection. PMID- 8470694 TI - Basics of computer hardware and software. AB - The basics of computer hardware and software are presented. A computer is a general-purpose electronic counting device used in data processing because of its accuracy and high speed. The physical components of a computer system are called the hardware, which includes the central processing unit and peripheral equipment for data input, output, and storage. Computer capacity is measured by the amount of data that can be stored in main memory and by the computer word size. Performance is indicated by the speed with which instructions are executed. Input devices (e.g., keyboard-type terminals) are the components that accept raw data and convert it into electronic form, and output devices (e.g., video display terminals) present the results of data processing in human-readable form. System software is the set of instructions that facilitate hardware use and allow the application software, which solves specific user problems, to run efficiently. System and application software is written by using various machine and symbolic languages. Milestones in software-development techniques include program subroutine use, modular programming, functional decomposition, structured programming, and structured analysis. Objectives in improving software quality are reducing development costs, making maintenance easier, and making development results more predictable. Because software development has lagged behind revolutionary advances in hardware, the full potential of computers has yet to be realized. PMID- 8470695 TI - Prescriptive ambivalence. PMID- 8470696 TI - Which catheter first? PMID- 8470698 TI - Why would an attorney hire a nurse? PMID- 8470697 TI - Peds pain protocols. PMID- 8470699 TI - Making headway with intracranial hypertension. PMID- 8470700 TI - 'End-of-life' care: patients' choices, nurses' challenges. PMID- 8470701 TI - Back stress isn't part of the job. PMID- 8470702 TI - Superior vena cava syndrome. PMID- 8470703 TI - How severe is this frostbite? PMID- 8470704 TI - Keeping an eye on magnesium. PMID- 8470705 TI - The new food label. PMID- 8470706 TI - Let's get our backs up. PMID- 8470707 TI - Evaluating needleless i.v. tubing. PMID- 8470708 TI - The changing face of rehabilitation nursing. PMID- 8470709 TI - Asserting a nurse's "comparative fault," a manufacturer won a 30% reduction in a $l50,000 award. PMID- 8470710 TI - Small change. PMID- 8470711 TI - The history of the National Eye Institute. PMID- 8470712 TI - The National Eye Institute. A quarter century of achievement. PMID- 8470713 TI - Clinical follow-up of phototherapeutic keratectomy for treatment of corneal opacities. AB - We performed phototherapeutic keratectomy with a 193-nm excimer laser on 18 sighted patients (18 eyes) to treat corneal opacities. The corneal opacities were caused by corneal dystrophies in five patients; corneal scars secondary to corneal ulcers in six patients; corneal scar secondary to trauma in four patients; and band keratopathy, atopy, or corneal calcification in three patients. Mean follow-up was eight months (range, two to 18 months). Corneal clarity improved in 14 of the 18 eyes (77.7%). Four patients, three with band keratopathy or calcification and one with postinfectious corneal scar, did not improve. Uncorrected visual acuity improved in 11 patients, did not improve in five patients (including the four patients in whom treatment failed), and decreased in another two patients, apparently because of an increase in irregular astigmatism. A hyperopic shift was observed in ten patients. None of the successfully treated eyes developed surface problems or recurrence of the disease during the follow-up. Phototherapeutic keratectomy thus appears to be a safe and effective alternative to penetrating keratoplasty in some patients with selected anterior stromal opacities. PMID- 8470714 TI - Corneal epithelial changes after excimer laser photorefractive keratectomy. AB - We used the specular microscope to investigate corneal epithelial changes after excimer laser photorefractive keratectomy. Thirteen patients underwent photorefractive keratectomy on one eye to correct myopia. We observed the central corneal epithelium of each eye at postoperative periods from one to 15 months after photorefractive keratectomy. The fellow eye served as a control. In 11 eyes (85%) the central cornea showed normal epithelial patterns. Two eyes had an abnormal epithelial pattern that included elongated epithelial cells. There were no difference in the mean cell area or coefficient of variation of mean cell area between the treated eyes and the control eyes. These results suggest that permanent destruction of Bowman's membrane caused by photorefractive keratectomy does not affect the morphologic characteristics of the most superficial layer of the corneal epithelium in most eyes. However, the presence of abnormal epithelial cell patterns in two patients should be considered a risk factor for this procedure. PMID- 8470715 TI - Corneal light scattering and visual performance in myopic individuals with spectacles, contact lenses, or excimer laser photorefractive keratectomy. AB - Corneal transparency and visual performance are currently receiving much attention after excimer laser surgery. To date, emphasis has been on comparison of eyes on which laser surgery has been performed to eyes with emmetropia. A more appropriate comparison should be between eyes on which laser surgery has been performed and eyes with other forms of correction for myopia. Forward-scattered light, back-scattered light, and visual acuity were investigated and data were collected from 35 myopic individuals with various types of correction for myopia (spectacles, hard and soft contact lenses, and excimer laser surgery). Forward scattered light was measured by using a new computerized technique, back scattered light was measured with a charge coupled device-camera system, and visual acuity was measured with a computerized system at various levels of contrast. Spectacles, hard contact lenses, and excimer laser surgery are all superior to soft contact lenses in terms of light scatter and low-contrast visual acuity and excimer laser photorefractive keratectomy produces comparable results to spectacles one year postoperatively. At low-contrast visual acuity, mean visual acuity was 2.45 minutes of arc for the spectacle wearers, 3.21 minutes of arc for the hard contact-lens wearers, and 5.04 minutes of arc for the soft contact-lens wearers. Excimer laser patients had a mean visual acuity of 9.04 minutes of arc three months postoperatively, and 2.53 minutes of arc after one year. A mean value of 2.4% contrast for forward light scatter was obtained for spectacle wearers compared with a level of 3.84% contrast for hard contact-lens wearers and 16.1% contrast for soft contact-lens wearers. The mean value for excimer laser patients was 20% contrast three months postoperatively and 2.1% contrast one year postoperatively. PMID- 8470716 TI - Comparison of the clinical performance of the Acuvue disposable contact lens and CSI lens in patients with giant papillary conjunctivitis. AB - Anecdotal reports have suggested that the use of disposable contact lenses is an effective treatment for giant papillary conjunctivitis. In a prospective randomized double-masked study, we compared the clinical performance of the Acuvue (Vistakon, Jacksonville, Florida) disposable contact lens to the traditional daily-wear lens of choice, CSI (Pilkington Barnes Hind, Sunnyvale, California), in 37 patients with previously diagnosed giant papillary conjunctivitis who were examined at one-month intervals for six months. A survey questionnaire for grading symptoms disclosed significant improvement in itching, discharge, and blurred vision in both groups early in the study. Evaluation of patient preference showed that the CSI lens was strongly preferred with regard to lens handling (76% vs 8%). In contrast, the Acuvue lens was strongly preferred with regard to lens comfort (62% vs 11%). For the variable of overall lens preference, there was no significant difference between the two lenses (CSI, 43% and Acuvue, 41%). Multiple regression analysis disclosed that both lens comfort (P < .002) and lens handling (P = .05) contributed significantly to the choices made regarding the dependent variable of overall lens preference. Lens comfort (beta = .71) was observed to be approximately 50% more powerful than lens handling (beta = .48). There was no significant difference in the rate or cost of torn lenses between groups, suggesting that the Acuvue lens can withstand the physical manipulation associated with daily-wear use for up to one month. The results of this study suggest that the use of disposable contact lenses for the treatment of giant papillary conjunctivitis is at least as effective as the traditional daily-wear lens of choice. PMID- 8470717 TI - Fungal invasion of seven hydrophilic contact lenses. AB - In six patients we reviewed the clinical, microbiologic, and histopathologic findings of seven hydrophilic contact lenses that had been infiltrated by fungi. Three patients had visual blurring or irritation and redness while wearing a contaminated lens; of these, two were unaware of any lens deposits. Three of the lenses from two patients were spares kept in storage for six months and one year, respectively. One contaminated lens had been torn and was kept in a case while a loaner lens was worn. Culture of this lens grew Cladosporium species. The contact lens case from one patient grew Penicillium species. Gross pathologic inspection disclosed multiple brown deposits in five lenses, multiple gray infiltrates in one lens, and a white infiltrate in one lens. Light microscopic examination disclosed partial-thickness (three lenses) or full-thickness (four lenses) invasion of the lens matrix by fungi, which contained granular, brown pigment in six lenses. PMID- 8470718 TI - Combined treatment of Acanthamoeba keratitis with propamidine, neomycin, and polyhexamethylene biguanide. AB - We developed an intensive treatment regimen of topical neomycin, propamidine, and polyhexamethylene biguanide that was tapered to a maintenance level over a 14- to 28-day period as toxicity developed. Since July 1991, we used this treatment on six eyes of five patients in whom Acanthamoeba keratitis was diagnosed clinically. All patients had positive cultures for microorganisms from their corneas or contact lens cases or had pathognomonic findings of pseudodendritic subepithelial infiltrates and radial keratone-uritis. After therapy, all patients improved within two to four weeks, with regression or resolution of neuritis and infiltrates, healing of epithelial defects, and lessening of pain. By three to four months, visual acuity had returned to 20/20 in all eyes. We believe the addition of polyhexamethylene biguanide to our treatment regimen in Acanthamoeba keratitis dramatically aided and hastened the clinical improvement in five consecutive patients and may, with early diagnosis, increase the number of medical cures. PMID- 8470719 TI - Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of ulcerative keratitis. AB - We evaluated the efficacy of ciprofloxacin (3 mg/ml) as the sole topical antibiotic used to treat infectious keratitis in 14 patients. We compared the ciprofloxacin-treated group to a retrospective control group of 30 consecutive culture-positive patients treated with conventional therapy in which cefazolin (50 mg/ml) and fortified gentamicin sulfate (9.1 mg/ml) solutions were used. We found no remarkable difference between the control group and the ciprofloxacin treated group regarding patient age, risk factors, need for hospitalization, and virulence of organism isolated. The average time to healing in culture-positive ciprofloxacin-treated patients was 34 +/- 33 days vs 45 +/- 71 days in the control group and this difference was not statistically significant. The duration of antibiotic therapy in the culture-positive ciprofloxacin-treated group was 27 +/- 15 days vs 33 +/- 50 days in the control group. Four of the 30 control patients required modification of their antibiotic regimen, whereas no ciprofloxacin-treated patient required a change. Ciprofloxacin appears to be an effective single agent in the treatment of ulcerative keratitis. PMID- 8470720 TI - Retrocorneal fibrous membranes in failed corneal grafts. AB - Histopathologic slides from 170 failed grafts, excised between 1983 and 1990 were reviewed. The overall incidence of retrocorneal fibrous membrane was 54% (92 grafts). The incidence of diffuse (extensive) retrocorneal fibrous membrane was 17% (29 grafts) and that of focal (peripheral) retrocorneal fibrous membrane was 37% (63 grafts). A high correlation was found between the clinical presence of peripheral anterior synechiae or vitreous adherent to the wound and the finding of retrocorneal fibrous membrane in aphakic and pseudophakic failed corneal grafts. A high correlation was also found between tube-shunt operation and the presence of diffuse retrocorneal fibrous membrane. Sixteen of 63 (25%) regrafted failed grafts, that is second grafts, with focal retrocorneal fibrous membranes failed within 18 months following surgery. Thirteen of 29 (45%) regrafted failed grafts with diffuse retrocorneal fibrous membrane failed within the same period and 11 of these (85%) were associated with tube-shunt surgery. PMID- 8470721 TI - Diffuse corneal clouding in siblings with fetal alcohol syndrome. AB - Three of four siblings born to parents with a history of heavy alcohol abuse had bilateral diffusely cloudy corneas at birth. These three siblings, who had mild systemic features of fetal alcohol syndrome, underwent corneal transplantations, and their specimens were examined by light and electron microscopy. Histologically, the alterations in Bowman's layer ranged from thickening to total loss. There were varying degrees of corneal stromal edema. The unique pathologic feature in the corneas was the anomaly of the anterior banded zone of Descemet's membrane, which was either absent, poorly formed, or thinned in the central and peripheral cornea. The corneal endothelium was attenuated or multilayered. The diffuse clouding and the range of histologic abnormalities in the corneas might be related to the maternal alcohol abuse. PMID- 8470722 TI - Immunohistopathologic features and therapy of conjunctival lichen planus. AB - Lichen planus is an autoimmune disease that typically involves skin and the mucosa of the genitalia and mouth. Conjunctival involvement is rare, and the microscopic abnormalities of affected conjunctivae are not well characterized. We treated two patients with cicatrizing conjunctivitis and extraocular conjunctival lichen planus confirmed by biopsy. We found irregular, thickened basement membrane with reduplications similar to the findings in oral mucosa affected by lichen planus. The absence of basement membrane immunoreactants excluded ocular cicatricial pemphigoid. Results of laboratory tests for collagen vascular diseases including sarcoidosis and lupus were also negative. Treatment with 2% cyclosporine eyedrops controlled inflammation and stopped cicatrization in one patient who was followed up for 12 months. The other patient, in whom lichen planus was recently diagnosed, responded favorably to topical cyclosporine. Lichen planus should be included in the differential diagnosis of cicatrizing conjunctivitis and its immunohistopathologic features should be studied in conjunctival biopsies. Topical cyclosporine may be used successfully for conjunctival lichen planus. PMID- 8470723 TI - Parapapillary chorioretinal atrophy in normal-pressure glaucoma. AB - Parapapillary chorioretinal atrophy has been shown to be associated with glaucomatous optic nerve damage. We sought to determine whether eyes with normal pressure glaucoma have an unusually large parapapillary atrophy as compared to eyes with primary open-angle glaucoma. Color stereoscopic optic disk photographs of 34 patients with normal-pressure glaucoma and 283 patients with primary open angle glaucoma were morphometrically analyzed. Both groups were matched for neuroretinal rim area and visual field loss. Severely myopic eyes were excluded. The parapapillary atrophy was differentiated into a peripheral Zone Alpha with irregular pigmentation and a central Zone Beta with visible sclera. Zones Alpha and Beta did not differ significantly between the two groups in either frequency or size. Eyes with normal-pressure glaucoma do not have an abnormally large parapapillary atrophy as compared to eyes with primary open-angle glaucoma, which is diagnostically and pathogenetically important. PMID- 8470724 TI - Late complications after glaucoma filtering surgery with adjunctive 5 fluorouracil. AB - We studied 105 patients (105 eyes) operated on for glaucoma with adjunctive fluorouracil, who were followed up for 12 to 48 months (mean, 34.6 +/- 12.9 months). Fifty eyes that had previous glaucoma or cataract extraction or had inflammatory glaucoma had a high risk for postoperative scarring (high-risk group), and 55 eyes had glaucoma surgery as an initial procedure (initial surgery group). An intraocular pressure of 20 mm Hg or less, with or without hypotensive medications, was found in 42 eyes in the high-risk group (84.0%) and in 53 of the eyes in the initial surgery group (96.4%). Of the 105 eyes, an intraocular pressure of 12 mm Hg or less without medication was achieved in 17 eyes in the high-risk group (34.0%) and in 35 eyes in the initial surgery group (63.6%). Late complications in both groups were as follows: endophthalmitis in four eyes (3.8%) (two of the infected blebs were located superiorly and two inferiorly), transient leaking bleb in two eyes (1.9%), hypotony of an extended period with 180 to 360 degrees of filtration in three eyes (2.9%), giant bleb extending over the cornea in two eyes (1.9%), and a transient, mild iridocyclitis in nine eyes (8.6%). Thus, adjunctive fluorouracil after filtering surgery may entail various, mainly bleb-related, late side effects and complications. PMID- 8470725 TI - Effect of desmopressin on aqueous humor flow in humans. AB - The rate of aqueous humor flow was studied in 17 human subjects with neurogenic diabetes insipidus. Flow was measured by fluorophotometry on two consecutive afternoons. The first day, subjects used desmopressin to control their diuresis; on the second day, subjects did not use desmopressin and had uncontrolled diuresis. On both days, one eye was treated with the beta-adrenergic antagonist, timolol. With desmopressin, the rate of aqueous humor flow in the untreated eye was 2.53 +/- 0.79 microliters/min (mean +/- standard deviation) and in the timolol-treated eye was 1.69 +/- 0.40 microliters/min. Without desmopressin, the rate of aqueous humor flow in the untreated eye was 2.34 +/- 0.69 microliters/min and in the timolol-treated eye was 1.53 +/- 0.43 microliters/min. Thus, the use of desmopressin was associated with a slightly higher rate of aqueous humor flow in both the normal and the beta-adrenergically inhibited eye (P = .05), and the suppression of aqueous humor flow associated with beta-adrenergic inhibition occurred with and without antidiuretic hormone (P < .001). The observed differences in aqueous humor flow on the two days could have been caused by a direct effect on the eye or to indirect effects, such as the change in plasma osmolality, which changed from 291 +/- 6 mOsm on the desmopressin day to 299 +/- 8 mOsm on the desmopressin-abstention day (P < .001). PMID- 8470726 TI - Therapy for ocular toxoplasmosis. AB - We conducted a prospective multicenter study of the efficacy of current therapeutic strategies for ocular toxoplasmosis in 149 patients. Treatment consisted of the following three triple-drug combinations: group 1, pyrimethamine, sulfadiazine, and corticosteroids; group 2, clindamycin, sulfadiazine, and corticosteroids; and group 3, trimethoprim, sulfamethoxazole and corticosteroids. Patients with peripheral retinal lesions were not treated systemically. No difference in the duration of inflammatory activity was observed between treated and untreated patients (P = .5). The most important factor predicting the duration of inflammatory activity was the size of the retinal lesion itself, independent of the treatment (P < .001). We found a reduction in size of the retinal inflammatory lesion for 49% of the pyrimethamine-treated patients (17 of 35) compared to 20% of the untreated patients (eight of 41) (P < .01). However, the most frequent occurrence of side effects was also associated with pyrimethamine medication (26%, nine of 35). The mean recurrence rate after three years of follow-up was 49% for all patients (60 of 122 patients), with no differences between treated and untreated patients (P = .6). PMID- 8470727 TI - Dystrophic calcification of silicone scleral buckling implant materials. AB - In six patients, removal of solid silicone scleral buckling implant materials that had been in place between eight and 21 years disclosed gray-white deposits firmly adherent to the silicone. Four of the six patients had culture-proven infections, whereas two had no evidence of infection and had negative cultures. One of these two patients, however, had intermittent pain, which was the indication for removal of the implant. Analysis of the deposits disclosed that they were calcium phosphate. The exact mechanism responsible for the calcification on the silicone material is unknown. Dystrophic calcification can occur without infection in injured tissue wherein extracellular deposits of devitalized cells, blood cells, and lipids may act as a nidus for calcification. In the presence of infection, bacteria may serve as such a nidus. Additionally, it is possible that biofilm produced by the bacteria had a role in the deposition of calcium phosphate, as well as in its firm adhesion to the silicone materials. We considered the possibility of similar deposits developing on intraocular silicone lenses. PMID- 8470728 TI - Clinical predictors of scleral rupture after blunt ocular trauma. AB - We conducted a two-part study to define better the clinical predictors of scleral rupture after blunt trauma. In part 1 we ascertained the prevalence of scleral rupture among a population of patients examined in an ophthalmic emergency room with severe blunt ocular trauma over a six-month period. Scleral rupture was diagnosed in ten of 283 patients (3.5%). In part 2 we compared the clinical findings in 29 patients with scleral rupture to those of 273 patients with no scleral rupture after blunt trauma. We noted that eyes with visual acuity of light perception or less, an intraocular pressure of 5 mm Hg or less, an abnormally deep or shallow anterior chamber, or a media opacity preventing a view of fundus details by indirect ophthalmoscopy, should be considered ruptured when severe intra- or periocular hemorrhage is present. This diagnostic algorithm had a sensitivity of 100.0% (98.7% to 100.0%), specificity of 98.5% (97.1% to 99.9%), and a positive predictive value of 71.4% (66.3% to 76.5%). PMID- 8470729 TI - Accurate ultrasonic biometry in pseudophakia. PMID- 8470730 TI - Exudative retinal detachment and retinal folds after trabeculectomy. PMID- 8470731 TI - Early manifestation of retinal hamartomas in tuberous sclerosis. PMID- 8470732 TI - HLA-A29 as a potential risk factor for nonarteritic anterior ischemic optic neuropathy. PMID- 8470733 TI - Metastatic renal cell carcinoma manifesting as an orbital mass. PMID- 8470734 TI - A newborn with posterior lenticonus. PMID- 8470735 TI - Development of object vision in infants with permanent cortical visual impairment. PMID- 8470736 TI - Ciprofloxacin-resistant bacterial keratitis. PMID- 8470737 TI - Hypotonous maculopathy after trabeculectomy with subconjunctival 5-fluorouracil. PMID- 8470738 TI - Hypotonous maculopathy after trabeculectomy with subconjunctival 5-fluorouracil. PMID- 8470739 TI - Improved productivity through purposeful use of additional template for a woman with cortical blindness. AB - A single-subject study with an ABAB design investigated an adaptation of a work activity through the purposeful use of an additional template to improve productivity for a woman with cortical blindness resulting from anoxic brain damage. The activity required the subject to outline brackets (as parts of a handi-rack woodwork project) by tracing a template on a piece of pine board. During the baseline phase of the study, the subject used one template to outline the brackets. During the intervention phase, the subject used an additional template after receiving a brief training in its use. Productivity was measured by the number of potentially usable outlined brackets. Data analysis revealed that in the intervention phases, productivity improved significantly and accuracy increased. The application of tapping the subjects' intact sensory system was valuable for determining her vocational potential. The rationale of using an additional template to improve productivity was explained by the theory of affordance. PMID- 8470740 TI - An abbreviated task-oriented assessment (Bay Area Functional Performance Evaluation). AB - The purpose of this study was to explore development of an abbreviated version of the Task-Oriented Assessment component of the Bay Area Functional Performance Evaluation (BaFPE). The BaFPE is widely used by occupational therapists practicing in mental health, but therapists have requested an instrument that could be administered and scored more quickly. Both a subjective and objective analysis support the development of an abbreviated version of the Task-Oriented Assessment. PMID- 8470741 TI - Contingent interaction during work and play tasks for mothers with multiple sclerosis and their daughters. AB - Occupational therapy has focused on activity as a catalyst for understanding human roles and interactions, regardless of whether disability or chronic illness is present. Parenting is an important interactional activity accompanied by specific role expectations. This investigation examined the interaction patterns of mothers with multiple sclerosis and their daughters. Thirty-one mothers with multiple sclerosis and their daughters aged 8 to 12 years were compared with 34 mothers without disabilities and their daughters aged 8 to 12 years. Videotaped mother-daughter interactions during a work task and a play task were scored by two raters for 11 different behaviors. These behaviors were collapsed into three behavioral composites--receptiveness, directiveness, and dissuasiveness--for statistical analysis. Statistical analysis revealed no significant differences between the two groups on the behavioral composites for either mothers or their daughters. The two tasks stimulated a different pattern of mother-daughter interactions. For both members of the dyad, interactions during the work task were more directive and less dissuasive than those in the play task. The clinical implication of this finding indicates the importance of understanding the influence of the task selected when observing interaction. Because of recent social and legal changes, understanding parenting and chronic illness is critical. PMID- 8470742 TI - Self-evaluation and self-concept of adolescents with physical disabilities. AB - Fifty-three adolescents aged 14 to 18 years with diagnoses of cerebral palsy (n = 27), cleft lip or palate or both (n = 17), or spina bifida (n = 9) took part in this study examining their self-esteem, self-concept, self-acceptance, social self-efficacy, and values, as measured by standardized instruments. Comparisons were made separately for males and females with norms developed for adolescents without disabilities. Significant differences were found only on several aspects of self-concept: females with physical disabilities were lower in perceived social acceptance, athletic competence, and romantic appeal than the normative sample, and males with physical disabilities were lower in perceived scholastic competence, athletic competence, and romantic appeal. In addition, social self efficacy was found to be a significant predictor of both independence and persistence in adolescents with disabilities, who were significantly less independent and persistent than were normative samples. The discussion focuses on the usefulness of the findings regarding social self-efficacy and the implications of the findings for occupational therapists. PMID- 8470743 TI - Clinical evaluation of the Hemi Wheelchair Cushion. AB - A foam cushion was designed for wheelchair users who propel their wheelchairs with the assistance of one lower extremity. It allows users to extend one hip to reach the ground without having to slide forward on the seat, thus maintaining a more erect posture. The cushion was evaluated to identify contraindications for its use. Eleven subjects (10 stroke patients and 1 patient with an above-the-knee amputation) were tested on the Hemi Wheelchair Cushion and on a second cushion chosen by their primary occupational therapists. Seat interface pressures, both before and after dynamic movement, sitting balance, and wheelchair mobility were measured for each cushion. An analysis of mean pressure values revealed no significant difference between the cushion (p = .80). Average pressures after dynamic movement showed a statistically significant difference from pressures before activity (p < .05). Subjective evaluation revealed that the Hemi Wheelchair Cushion did not adversely affect sitting balance or wheelchair mobility, and no contraindications for its use were identified. The results of this clinical evaluation indicate that the Hemi Wheelchair Cushion is an economical and appropriate option for wheelchair users who propel themselves with the assistance of one leg. PMID- 8470744 TI - A model to promote activity competence in elders. AB - This paper describes an occupational therapy home-based intervention in which purposeful activities were used to promote adaptation and competence in older adults with chronic disabilities. Seven home care therapists visited 17 randomly selected, community-living elders who were chronically disabled and who volunteered to participate in the program. The number of visits ranged from 3 to 10 and occurred over a 3-month period according to clients' needs and wishes. Therapists enhanced their ability to enter the client's social and cultural system by using participant-observation techniques and collaboratively identified activities. Therapists documented each home visit with a structured fieldnote form. An analysis of 112 field-notes indicated that therapists were able to understand a client's needs; this understanding resulted in small qualitative gains in areas identified as important by the client. Reilly's concept of an activity continuum was a useful framework from which to work with this population. The implications for program development, treatment outcomes, and accountability with this approach promote improved future treatment planning with the elderly with chronic disability. PMID- 8470745 TI - An analysis of a board game as a treatment activity. AB - Occupational therapists often use tabletop board games in treatment to help adult clients with physical disabilities improve the perceptual, cognitive, sensory, and fine motor skill components of occupational behavior. Detailed activity analyses of these types of activities, including performance norms, are not available in the occupational therapy literature. Such analyses would help therapists consider the multiple skill demands of tabletop games and allow more systematic grading of these treatment activities. This paper presents a model for analyzing therapeutic activities in relation to relevant motor learning and cognitive-perceptual literature. Included in this analysis are a description of the activity, examination of its component skills and of the qualitative features of activity performance, suggestions for grading and for treatment goals, and some preliminary performance standards derived from a pilot study of 18 adults without physical disabilities. The issue of transfer of skills between games and functional activities is also discussed. PMID- 8470746 TI - Generalization of occupational therapy effects in psychiatric rehabilitation. AB - Psychoeducation procedures dominate the treatment used by occupational therapists in psychiatric rehabilitation. The underlying assumption of skills training is that the skills taught generalize, that is, they persist beyond the treatment session and are used by the client in the community. This paper surveys occupational therapy literature to evaluate the generalization of skills taught to adult psychiatric clients by occupational therapists. Of the 77 studies reviewed, only 13 (17%) mentioned anything related to generalization. Seven of these articles statistically evaluated the outcome of skills training, but only four specifically assessed generalization of therapy. It is concluded that occupational therapists in psychiatry predominantly do not assess generalization of therapy. Discussion focuses on how four classes of generalization strategies (modifying the community environment, modifying the therapy environment, altering the style of therapy, and promoting client involvement) can enhance the effectiveness of occupational therapists in psychiatry. PMID- 8470747 TI - Linking patient and family stories to caregivers' use of clinical reasoning. AB - Due to pressures inherent in the current health care environment, health professionals' interactions with patients may be limited to attending to the disease process by using the scientific method of clinical reasoning. Health professionals may find it difficult to break out of this pattern of reductionistic thinking and acting to use other forms of clinical reasoning and to elicit patients' perceptions of the illness experience. Older adults and their families are particularly susceptible to being treated in a routine, disease focused manner. A growing body of literature gives voice to the stories and concerns of these persons. The purposes of this paper are to discuss thinking and clinical reasoning from several perspectives and to identify selections from literature that enhance understanding of the need to pay attention to both the disease and the illness experience and to use all forms of clinical reasoning. PMID- 8470748 TI - Training for a patient with shoulder disarticulation. AB - This patient received 26 outpatient occupational therapy sessions for a total of 32.5 hr during an 18-week period. All treatment goals were achieved with the exception of psychosocial adjustment issues, which are ongoing. He made significant gains in right upper quadrant muscle isolation and demonstrated control and strength of the upper, middle, and lower trapezius fibers adequate for a myoelectric prosthetic. He also made improvement with left manual dexterity and unilateral coordination with regard to activities of daily living. He was discharged from outpatient occupational therapy services and referred to another medical center for prosthetic evaluation. Twenty weeks after discharge from our facility, he returned for a follow-up visit. He had been fitted with a shoulder cap and his tolerance for wearing it was approximately 10 hr per day. Thirteen weeks after the follow-up visit he resumed outpatient occupational therapy. We are evaluating his tolerance to the placement of a passive arm to the shoulder cap. PMID- 8470749 TI - A personalized communication wallet. PMID- 8470750 TI - Enhancing the research image of occupational therapy. PMID- 8470751 TI - Dangers inherent in the partition of occupational therapy and occupational science. PMID- 8470752 TI - Variation among early Homo crania from Olduvai Gorge and the Koobi Fora region. AB - Fossils recognized as early Homo were discovered first at Olduvai Gorge in 1959 and 1960. Teeth, skull parts and hand bones representing three individuals were found in Bed I, and more material followed from Bed I and lower Bed II. By 1964, L.S.B. Leakey, P.V. Tobias, and J.R. Napier were ready to name Homo habilis. But almost as soon as they had, there was confusion over the hypodigm of the new species. Tobias himself suggested that OH 13 resembles Homo erectus from Java, and he noted that OH 16 has teeth as large as those of Australopithecus. By the early 1970s, however, Tobias had put these thoughts behind him and returned to the opinion that all of the Olduvai remains are Homo habilis. At about this time, important discoveries began to flow from the Koobi Fora region in Kenya. To most observers, crania such as KNM-ER 1470 confirmed the presence of Homo in East Africa at an early date. Some of the other specimens were problematical. A.C. Walker and R.E. Leakey raised the possibility that larger skulls including KNM-ER 1470 differ significantly from smaller-brained, small-toothed individuals such as KNM-ER 1813. Other workers emphasized that there are differences of shape as well as size among the hominids from Koobi Fora. There is now substantial support for the view that in the Turkana and perhaps also in the Olduvai assemblages, there is more variation than would be expected among male and female conspecifics. One way to approach this question of sorting would be to compare all of the new fossils against the original material from Olduvai which was used to characterize Homo habilis in 1964. A problem is that the Olduvai remains are fragmentary, and none of them provides much information about vault form or facial structure. An alternative is to work first with the better crania, even if these are from other sites. I have elected to treat KNM-ER 1470 and KNM-ER 1813 as key individuals. Comparisons are based on discrete anatomy and measurements. Metric results are displayed with ratio diagrams, by which similarity in proportions for several skulls can be assessed in respect to a single specimen selected as a standard. Crania from Olduvai examined in this way are generally smaller than KNM-ER 1470, although OH 7 has a relatively long parietal. In the Koobi Fora assemblage, there is variation in brow thickness, frontal flattening and parietal shape relative to KNM-ER 1470.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8470753 TI - Further observations on a method for estimating hominoid dental developmental patterns. AB - Several recent studies have concluded that early hominines resembled apes in patterns of dental ontogeny and have inferred from this conclusion that they were ape-like in other aspects of growth and development as well. Prior to their employment on fossil juveniles, the comparative methods used in these studies were not first tested for their predictive accuracy in distinguishing modern humans from apes on the basis of proposed patterns of dental ontogeny. We find that 92% of a sample of 48 modern children are classified as ape-like or nonhuman by the criteria employed in one of these studies and overlap entirely with fossil juvenile dental patterns. The use of these methods to characterize early hominines as "ape-like" or distinctly divergent from humans is thus shown to be unwarranted. PMID- 8470754 TI - Cranial deformation and nonmetric trait variation. AB - Cranial deformation is known to influence many traditional craniometric variables, but its effects on nonmetric trait variation are not well characterized. In this study, we examine the effects of three types of deformation (annular, lambdoid flattening, and fronto-occipital) on nonmetric traits, using a large sample of protohistoric and prehistoric crania. Our results indicate that a few traits are increased or decreased in relative frequency by particular types of deformation, but that these effects have little impact on the calculation of biological distances between groups. PMID- 8470755 TI - Nonmetric cranial variation and the populational affinities of the Pacific peoples. AB - Nonmetric traits of Hawaiian and Chamorro skulls were examined for evidence bearing on their populational affinities. Distance analyses reveal that the Hawaiian and Chamorro people, although not very near each other, are both closer to the East Asian than to the Jomon-Ainu or to the Arctic peoples. Our study of nonmetric cranial variation does not suggest an affinity between the Jomon and Pacific peoples. PMID- 8470756 TI - Differences in physical growth of Aymara and Quechua children living at high altitude in Peru. AB - Physical growth of Amerindian children living in two Aymara and three Quechua peasant communities in the Andean highlands of southern Peru (altitude 3,810 3,840 m) was studied, taking into account differences in the microclimate, agronomic situation, and sociodemographic variables. Anthropometric measurements were taken in 395 children aged under 14 years of age in a sample of 151 families in these communities, who were surveyed for sociodemographic variables as well. Data on the land system were available for 77 families. In comparison with reference populations from the United States (NCHS) and The Netherlands, stature, weight, head circumference, and midupper arm circumference (but not weight for stature) in the sample children were reduced. Growth retardation increased after the age of 1 year. Stature and weight in the present sample were very similar compared with previously published data on growth of rural Aymara children living near Lake Titicaca in Bolivia. Head circumference, midupper arm circumference, and weight for stature were significantly larger in Aymara children compared with Quechua children. Land was significantly more fragmented in Aymara compared with Quechua families, but amount of land owned was not different. Perinatal and infant mortality was elevated in Aymara vs. Quechua communities. Most families in Aymara communities used protected drinking water. One Quechua community had a severe microclimate, grim economic outlook, and weak social cohesion. Children in this community showed significant reductions in weight and midupper arm circumference compared with their peers in the other communities. We conclude that (presumably nutritionally mediated) intervillage and Aymara-Quechua differences in childhood physical growth existed in this rural high-altitude population in Peru and were associated with microclimate and the village economy, sociodemographic factors, and differences in the land system. PMID- 8470757 TI - Partial skeleton of Proconsul nyanzae from Mfangano Island, Kenya. AB - A partial skeleton attributed to Proconsul nyanzae (KNM-MW 13142) is described. The fossils were found at a site on Mfangano Island, Kenya, which dates to 17.9 +/- .1 million years ago. KNM-MW 13142 consists of six partial vertebrae (T12 S1), a nearly complete hipbone, most of the right femur and left femoral shaft, a fragmentary tibia and fibula, and a nearly complete talus and calcaneus. This skeleton provides the first pelvic fossil known for any East African Miocene hominoid. The new Proconsul specimen is compared to a large sample of extant anthropoids to determine its functional and phylogenetic affinities. In most aspects of its anatomy, KNM-MW 13142 closely resembles nonhominoid anthropoids. This individual had a long, flexible spine, narrow torso, and habitually pronograde posture, features characteristic of most extant monkeys. Evidence of spinal musculature suggests a generalized condition intermediate between that of cercopithecoids and hylobatids. The hindlimb of KNM-MW 13142 exhibits relatively mobile hip and ankle joints, with structural properties of the femur like those of hominoids. This mix of features implies a pattern of posture and locomotion that is unlike that of any extant primate. Many aspects of the Proconsul nyanzae locomotor skeleton may represent the primitive catarrhine condition. PMID- 8470758 TI - Primary lymphoma of the small intestine. A clinicopathological study of 119 cases. AB - Small bowel lymphomas account for 20 to 40% of primary gut lymphomas in Western populations and are among the most common malignant tumours of the small bowel. We studied 119 cases of primary small bowel lymphoma presenting over 4 decades. Two thirds of the patients were men with a peak age incidence in the 7th decade. Common presenting features included abdominal pain, weight loss, small bowel obstruction, and acute abdomen. Tumours were classified using the Kiel European Association for Haematopathology Geneva Workshop scheme and phenotyped on paraffin sections; 66% were B cells, and 34% were T cell. In all cases, the antibodies L26 and polyclonal CD3 reliably distinguished between B- and T-cell tumours. Of the B-cell lymphomas, 62% were diffuse high grade, 20% were low-grade lymphomas of mucosa-associated lymphoid tissue, 11% had both low- and high-grade components, and 7% were other low-grade types. Of the T-cell lymphomas, 83% were high grade, and 49% were enteropathy associated. Most T-cell lymphomas were ulcerated plaques or strictures in the proximal small bowel; B-cell lymphomas tended to be annular or polypoid masses in the distal and terminal ileum. Survival data showed that low-grade B-cell lymphomas had the best outcome and T cell lymphomas the worst. Adverse prognostic features included perforation, high grade histology, multiple tumours and advanced stage. PMID- 8470759 TI - Childhood rhabdomyosarcoma with anaplastic (pleomorphic) features. A report of the Intergroup Rhabdomyosarcoma Study. AB - The pleomorphic subtype of rhabdomyosarcoma (RMS) is now rarely diagnosed in both children and adults. Most cases previously called pleomorphic RMS are probably diagnosed as something else, most often embryonal RMS in children and malignant fibrous histiocytoma in adults. To analyze the concept of pleomorphic RMS in children, we reviewed the tumors of patients entered on the Inter-group Rhabdomyosarcoma Study (IRS I, II, and III). The presence of cells with lobated, hyperchromatic nuclei at least three times larger than the common tumor cell population (anaplastic cells) was selected as the main criterion. Of about 3,000 cases, 110 showed these types of cells, had sufficient histologic material, and had available follow-up data. These tumors were divided into two subgroups: Subgroup I tumors contained only scattered anaplastic cells, and tumors with foci or large sheets of anaplastic cells were classified as subgroup II. Besides the anaplastic-pleomorphic areas, most of these tumors had distinctive features of embryonal RMS (105 cases) and rarely had characteristics of alveolar RMS (five cases). The age distribution of these patients did not differ significantly from those whose tumors did not show the anaplastic features, the average being 6 years and the median 4 years. Lower extremity, retroperitoneum, and the head and neck region were the most common primary tumor sites. The 5-year survival rate was 60% for subgroup I tumors and 45% for subgroup II tumors compared with the survival rate of 68% for 482 IRS II embryonal RMS cases with no anaplastic pleomorphic features. The lower survival rate for patients in subgroup II was statistically significant (p = 0.004) and similar to the unfavorable survival of patients with alveolar RMS and undifferentiated sarcoma. Because anaplastic cells are seen in many soft tissue sarcomas and in both embryonal and alveolar RMS in children, this feature is not sufficiently unusual to separate a pleomorphic subtype of RMS. The presence of anaplastic cells in aggregates or diffuse sheets throughout the tumor, however, portends a poor survival for these patients. PMID- 8470760 TI - Crystal-storing histiocytosis associated with lymphoplasmacytic neoplasms. Report of three cases mimicking adult rhabdomyoma. AB - Massive crystal deposition is rare in lymphoplasmacytic (LPc) or plasma cell neoplasms. We report three cases in which the accumulation of crystals in histiocytes closely reproduced the histologic features of adult rhabdomyoma. The patients, all female, aged 18, 77, and 78 years, presented with tumor of cervical lymph nodes (two cases) or the otolaryngic mucosa (two cases). In addition, two patients had monoclonal serum or urine immunoglobulin (IgM-kappa-1, unknown-1), and one had renal and bone marrow involvement on biopsy. This last patient died of acute renal failure at 5 months, another was alive without disease at 8 years, and the remaining one was lost to follow-up. Lymph nodes, mucosae, and kidney showed a neoplastic LPc infiltrate masked by sheets of large benign histiocytes containing sheaves of crystals. Paraffin-section immunohistochemistry demonstrated monoclonal staining of the LPc cells in all cases (IgM-kappa-2, IgA kappa-1) and of the crystals (IgM-kappa) in one case. In all patients, the crystal-containing cells were positive for KP-1 (CD68), but not for desmin, muscle-specific actin, or myoglobin. These findings suggest that, in any case of adult rhabdomyoma in which the histologic findings are not typical, a crystal storing histiocytosis should be ruled out: recognition of the atypical LPc component and the histiocytic immunophenotype of the crystal-storing cells will help prevent a serious misdiagnosis. PMID- 8470761 TI - Complete histologic serial sectioning of a prostate gland with adenocarcinoma. AB - Variations in the proportion of surface occupied by tumor (percentage carcinoma), carcinoma volume, histologic grade, capsular penetration, and margin positivity were assessed in a completely sampled cancerous prostate gland. All prostatic tissue was embedded and each block serially sectioned, for a total of 2,678 histologic sections examined. Although variations in percentage carcinoma and carcinoma volume were noted in some blocks, the differences were small when compared with the initial set of 19 slides. Histologic Gleason's grade also showed little variation in the serial sections. Focal capsular penetration in one block and an increase in the number of blocks with a positive anterior margin from two to four were identified in serial sections, but this did not alter the pathologic stage because of seminal vesicle involvement by tumor. In this example, the morphologic prognosticators of tumor volume, histologic grade, margin positivity, and pathologic stage were not altered by complete serial sectioning. PMID- 8470762 TI - Idiopathic retroperitoneal fibrosis is a macrophage-rich process. Implications for its pathogenesis and treatment. AB - Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease of obscure etiology and pathobiology. Using sections of frozen and paraffin-embedded tissue, an immunohistochemical technique, and antibodies to a variety of macrophage- and lymphocyte-associated antigens, we studied six examples of IRF. The results showed a large population of spindle-shaped cells that expressed the immunophenotype of a tissue macrophage, that is, Leu 3a,b (CD4)+, MY7 (CD13)+, Leu M5 (CD11c)+, KP-1 and EBM-11 (CD68)+, human leukocyte antigen (HLA-DR)+, leukocyte common antigen (CD45)+, HAM-56+, and MAC387+. A subpopulation of these cells also reacted with an antibody to the "activation" antigen, interleukin 2R (CD25). A control group of "fibroblastic" lesions including keloids, desmoid tumors, and an aggressive fibromatosis displayed minimal reactivity with this panel of antibodies. The abundance of macrophages suggests that they may play an important role in the pathogenesis of IRF. If, as has been suggested by some studies, IRF is an immune-mediated phenomenon, the macrophages may be triggered to produce cytokines that stimulate fibroblast proliferation and subsequent fibrosis that characterize this disease. PMID- 8470763 TI - Lymphocytic bronchitis/bronchiolitis in lung allograft recipients. AB - Twenty-six cases of lymphocytic bronchitis/bronchiolitis (LBB) identified by transbronchial biopsy in 25 lung allograft recipients were studied to determine its relationships to acute rejection and bronchiolitis obliterans (OB). LBB occurred 355 days after transplantation on average (range, 15-2,118 days) and was manifested by a patchy or diffuse submucosal infiltrate of lymphocytes and plasma cells, which percolated deep to the smooth muscle layer of the bronchi in 15 cases. Submucosal granulation tissue and bronchiolitis were observed more frequently in patients who developed OB than in those who did not (44% and 88% vs 23% and 41%). Although 39% of patients progressed to OB overall, the majority of patients with LBB who received augmented immunosuppressive therapy (steroids, antithymocyte globulin, or both) improved or stabilized their pulmonary function abnormalities. Interestingly, LBB was preceded by acute rejection in 20 of 26 instances, and LBB frequently persisted as a histologic finding after the initial diagnostic transbronchial biopsy. LBB appears to be related to previous acute rejection episodes and responds to augmented immunosuppressive therapy. PMID- 8470764 TI - Eosinophilic and lymphoeosinophilic cholecystitis. AB - Eosinophilic cholecystitis (EC) is an infrequent and poorly understood inflammatory condition of the gallbladder. First described in 1949, EC may be defined as an inflammatory condition of the gallbladder in which the inflammatory infiltrate is composed predominately of eosinophils so that their presence clearly overshadows the presence of any other inflammatory cell component. In the few reports that describe EC, it has been described in association with acalculous cholecystitis, with subacute cholecystitis lasting 2 to 3 weeks and with several forms of drug therapy. This retrospective clinicopathologic study reviewed the histopathologic features of 217 consecutive cholecystectomy specimens with special clinical reference to the timing of gallbladder removal after symptoms, previous drug therapy, systemic infection, and the presence of cholelithiasis. Pathologically, 48 of these cases (22.2%) contained eosinophils to some degree. Eosinophilic cholecystitis was diagnosed in 14 (6.4%) of the specimens, and another 14 (6.4%) specimens demonstrated substantial numbers of eosinophils but also had other types of inflammatory cells in abundance, including neutrophils and lymphocytes. Of the eight patients with acalculous cholecystitis, six had substantial eosinophils in their gallbladders, whereas the other two patients had no eosinophils. In this study, EC was more prevalent than in other reported series, and it did not show any association with the timing of gallbladder removal after initial symptoms, drug therapy, or other preexisting medical conditions. Eosinophilic cholecystitis is more common than previously recognized and probably represents a subgroup of patients with a unique or hypersensitivity type of inflammatory response to altered bile. Large numbers of eosinophils in the inflammatory infiltrate occurred three times more commonly in patients with acalculous cholecystitis than in patients with cholelithiasis. PMID- 8470765 TI - Calcifying fibrous pseudotumor. AB - We report 10 cases of a distinctive benign fibrous lesion characterized by the presence of abundant hyalinized collagen with psammomatous or dystrophic calcifications and a lymphoplasmacytic infiltrate. The lesions were present from 2 months to 10 years before resection and ranged in size from 2.5 to 15 cm. They involved subcutaneous and deep soft tissues and, although relatively well circumscribed, occasionally infiltrative borders or entrapped structures were seen on microscopic examination. The lesions were located in the extremities (three cases), trunk (two cases), scrotum (two cases), groin (one case), neck (one case), and axilla (one case). Both sexes were equally affected. The mean and median ages of the patients were 16.2 and 18.5 years, respectively (range, 1 to 33 years). All cases were initially managed by simple local excision. Follow-up ranging from 2 months to more than 10 years (median, 41.5 months) was available in six cases and revealed a local recurrence in one instance; this became clinically apparent about 7.5 years after the initial resection. Morphologic features and follow-up data suggest this may be a unique form of fibrous pseudotumor. PMID- 8470766 TI - Postimmunization (vaccination) injection-site reactions. A report of four cases and review of the literature. AB - Four patients each had a single subcutaneous nodule at the site of a previous vaccine injection; three after injection of diphtheria, tetanus, and pertussis vaccination and one after tetanus toxoid vaccination. Presentation was with a mass 4-22 months after vaccination at the site of injection. Histologically, three patients had a necrotizing granulomatous reaction with a surrounding infiltrate of lymphocytes, plasma cells, histiocytes, and associated fibrosis. The fourth patient demonstrated a lymphohistiocytic reaction with a predominance of histiocytic cells as well as associated plasma cells, fibroblasts, and fibrosis. The lymphoid infiltration in these reactions showed a predominance of T lymphocytes over B-lymphocytes. Aluminum was demonstrated in necrotic foci, inflammatory stroma, and the granular cytoplasm of histiocytes with the aid of solochrome azurine and solochrome cyanine stains as well as by energy-dispersive x-ray microanalysis. The reactions are thought to be immunologic (hypersensitivity) reactions associated with the aluminum contents of the preparation. PMID- 8470767 TI - Paratesticular (spermatic cord and tunica testis) fibroblastic/myofibroblastic proliferations. PMID- 8470768 TI - Prostate in ovarian teratoma. PMID- 8470769 TI - PNET vs MPNST. PMID- 8470770 TI - Charting a course for the future: a society at the interface. PMID- 8470771 TI - Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in dengue-infected patients. AB - Sensitive immunoenzymatic assays were used to study the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta in sera from dengue infected patients obtained during the 1989-1990 outbreak of dengue-3 in Tahiti, French Polynesia. The patients, both children (n = 47) and adults (n = 18), were clinically classified as having dengue hemorrhagic fever (DHF) and graded according to the severity of illness (grade I = fever, grade II = fever with spontaneous hemorrhagic manifestations, grade III = circulatory failure, grade IV = deep shock). The serum samples were obtained from day 1 to day 10 after the onset of the disease. High levels of TNF-alpha were observed in dengue-infected children of all severity grades. The highest values of TNF-alpha were found before day 6 after the onset of the infection, these values decreased from day 6 to day 10. The highest values were observed in sera from grade III and IV patients. High values of IL-6 were observed in serum samples of grade I and II patients on day 1, which decreased on day 4, and by day 5 were similar to those obtained from 25 control children. In grade III and IV patients, the highest values of IL-6 were observed from day 3 to day 5 after the onset of infection; after day 5, these values were very low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470772 TI - Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy. AB - The major cause of morbidity and mortality in Chagas' disease is a chronic inflammatory cardiomyopathy, which presents ten or more years following initial infection. Demonstration of Trypanosoma cruzi in cardiac tissue by routine microscopy or culture is difficult in these patients, which has suggested that persistent organisms are not required for chronic disease. Consequently, studies have focused on elucidating an autoimmune pathogenesis of chronic injury. To further assess the persistence of T. cruzi in host tissue, DNA extracted from formalin-fixed, paraffin-embedded autopsy specimens from seronegative or seropositive patients was amplified by the polymerase chain reaction using T. cruzi-specific primers. Trypanosoma cruzi DNA sequences were not consistently amplified from four seropositive patients who lacked evidence of fatal chronic chagasic cardiomyopathy (CCC) (0 positive of 12 heart samples, 0 positive of four gonadal samples, and 0 positive of four adrenal samples) or nine seronegative patients (0 positive of 27 heart samples, 0 positive of nine gonadal samples and 0 positive of nine adrenal samples). In seven seropositive patients with severe CCC, cardiac tissue adjacent to inflammatory infiltrates yielded amplified T. cruzi DNA sequences in 18 of 21 heart samples. Parallel testing of gonadal and adrenal tissues from these same patients produced detectable T. cruzi DNA in none of the gonadal tissue samples and one of the seven adrenals. Our studies demonstrate that T. cruzi, or a portion of its genome, is present in the inflammatory lesion of chronic cardiac Chagas' disease. PMID- 8470773 TI - Risk factors of malaria infection during pregnancy in Burkina Faso: suggestion of a genetic influence. AB - A cohort of 570 untreated pregnant women from Burkina Faso was studied to assess the influence of epidemiologic factors on malaria infection, which was quantified as the mean of serial, season-adjusted parasitemia measurements (mean parasite density [MPD]) carried out during the last five months of gestation. A significant effect of the area of maternal residence on the MPD was found (P < 0.003) and was probably due to geographic differences in mosquito transmission conditions. The strong relationship observed between parity and malaria infection (P < 0.0001), with MPD levels decreasing as the number of gestations increased, confirms that primigravidae are a high-risk group whose protection should be a priority. After adjustment for two relevant epidemiologic factors (i.e., area of residence and parity), the residual MPD values fitted a mixture of two distributions. This result supports the view that a major gene is involved in the determination of malaria infection intensities and is consistent with the results of a recent familial study in Cameroon. PMID- 8470774 TI - Plasmodium falciparum-associated anemia in children at a large urban hospital in Zaire. AB - Chloroquine-resistant Plasmodium falciparum malaria and human virus (HIV) infection through blood transfusions used to treat malaria-associated anemia are causes of increasing morbidity and mortality among children in Africa. To evaluate the role of malaria and other risk factors for pediatric anemia, we conducted a study of children brought to the emergency ward of a large urban hospital in Kinshasa, Zaire. A total of 748 children ages six through 59 months were enrolled; 318 (43%) children were anemic (hematocrit < 33%), including 74 (10%) who were severely anemic (hematocrit < 20%). Plasmodium falciparum parasites were detected in 166 children (22%); hematocrits for these children (mean 25.8%) were significantly lower than for aparasitemic children (mean 33.7%; P < 10(-6)). Fever with splenomegaly (odds ratio [OR] = 6.5, P = 0.02), parasitemia (OR = 3.5, P < 0.001), lower socioeconomic status (OR = 2.0, P = 0.004), and malnutrition (OR = 1.8, P = 0.06) were independently associated with anemia in a multivariate model. Recent antimalarial therapy was also associated with a lower hematocrit, suggesting that chloroquine may have aggravated the anemia. A reassessment of the effectiveness of strategies to diagnose and treat malaria and malnutrition is necessary to decrease the high prevalence of anemia and the resultant high rate of blood transfusions in areas endemic for malaria and HIV. PMID- 8470775 TI - Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo. AB - The antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum. In vitro, the mean 50% inhibitory concentration (IC50) for beta-artemether was 1.74 nM (range 1.34-1.81 nM), and this value for beta-arteether was 1.61 nM (range 1.57-1.92 nM). They were approximately 2.5-fold more potent than artemisinin, which had a mean IC50 of 4.11 nM (range 3.36-4.60 nM). In the mouse model, the 50% curative doses (CD50) of beta-artemether and beta-arteether had a mean value of 55 mg/kg (32-78 mg/kg). The 50% effective curative doses (ED50) in the Aotus monkey were 7.1 mg/kg (95% confidence interval [CI] = 3.7-13.5) for beta-artemether and 11.8 mg/kg (95% CI = 6.5-21.3) for beta-arteether. Overall, the activities of the two drugs were comparable. PMID- 8470776 TI - Derivation of highly mefloquine-resistant lines from Plasmodium falciparum in vitro. AB - Serial passage of a multidrug-resistant clone of Plasmodium falciparum in concentrations of mefloquine hydrochloride ranging from 30 to 2,400 ng/ml resulted in the derivation of increasingly resistant parasite lines in vitro. Parasite lines isolated in mefloquine concentrations greater than 300 ng/ml demonstrated increased vacuolization, enhanced pigment production, and increased growth rates as compared with the progenitor clone, W2-mef. Although microdilution incorporation assays demonstrated that the 50% inhibitory concentration (IC50) of mefloquine were similar for all lines, the IC90, IC95, and IC99 levels were significantly increased. Growth rate assays performed in 5% hematocrit suspensions demonstrated different levels of mefloquine resistance among these lines. Under these conditions the most resistant line, Mef 2.4, grew efficiently in approximately 10-fold higher concentrations of mefloquine than the progenitor clone W2-mef. Analysis of drug susceptibility profiles to mefloquine hydrochloride, chloroquine diphosphate, quinine sulfate, and halofantrine hydrochloride indicated that selection for high levels of mefloquine resistance had resulted in significant increases in resistance to halofantrine and increased sensitivity to chloroquine. The phenotypic changes demonstrated in the most resistant line, Mef 2.4, reflect a multidrug resistant-like phenotype, and appear to mimic changes recently reported in drug susceptibility profiles of recrudescent isolates following mefloquine treatment failures in Thailand. PMID- 8470777 TI - Treatment of malaria in Vietnam with oral artemisinin. AB - In this study, 638 patients with either Plasmodium falciparum or P. vivax malaria were treated with artemisinin (qinghaosu) that was isolated and formulated into tablets and capsules in Vietnam. In all cases, artemisinin treatment resulted in a rapid clearance of parasitemia and fever. Recrudescence rates were highest in those groups receiving treatment for five or less days (50%), but were between 10% and 23% for those groups receiving the drug for 5-10 days. A low recrudescent rate (9.5%) was also found when patients were treated with a combination of artemisinin for three days and tetracycline for five days. Thus, artemisinin represents a useful and economically feasible component of the malaria control program in Vietnam. PMID- 8470778 TI - Human immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) after a decrease in malaria transmission in Madagascar. AB - A resurgence of falciparum malaria occurred in the central highlands of Madagascar in the 1980s and was responsible for an outbreak in 1986-1987. Since 1989, transmission has decreased dramatically. In April 1991, we investigated the humoral and cellular immune responses of 53 inhabitants of the village of Manarintsoa to six synthetic peptides that reproduced the major B and/or T cell epitopes of the Pfl 55/ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum. The presence of RESA peptide-reactive T cells was assessed by lymphocyte proliferation assay as well as by detection of in vitro production of interferon-gamma and interleukin-2. The mean values of these cellular responses were low, and the results obtained in these three tests showed no correlation. Twenty-seven subjects presented with anti-RESA antibodies as detected by modified immunofluorescent assay, but the mean levels of anti-peptide antibodies were low. When compared with data obtained in January 1988 from the same subjects with three of the six peptides, the present data demonstrated a decrease in the response to these peptides in terms of both proliferative response and mean antibody titers. The mean values of anti-RESA antibodies remained unchanged. The fact that cellular and humoral responses to the major Pfl 55/RESA epitopes decreased but did not disappear probably reflects both the remainder of the acquired immunity resulting from the 1986-1987 malaria outbreak, and its conservation by the very low level of transmission since 1989. PMID- 8470779 TI - Detection of West Nile virus by the polymerase chain reaction and analysis of nucleotide sequence variation. AB - A polymerase chain reaction (PCR) assay was developed to rapidly detect and identify West Nile (WN) virus. The RNA from seven isolates of WN virus from six countries and four other flaviviruses (Kunjin, Japanese encephalitis, St. Louis encephalitis, and yellow fever viruses) was reverse-transcribed (RT) and amplified by PCR. The nucleotide sequences of the amplified products were determined by a rapid, automated DNA sequencing method. The WN virus RT/PCR assay detected the target gene segment of sequencing method. The WN virus RT/PCR assay detected the target gene segment of isolates from both the African-Middle Eastern group and the Indian group with a sensitivity of approximately 0.05 pg of viral RNA. Kunjin virus was the only other flavivirus tested that produced a band of the appropriate size. Five of seven WN virus isolates showed 92-98% homology in the nucleotide sequence of their PCR products. The sequence of one isolate was virtually identical to the published sequence of the Nigerian isolate (99.5% homology). No correlation was established between the degree of nucleotide homology, geographic location, time of isolation, or source of the isolates. PMID- 8470781 TI - [A modification of the Macintosh blade for difficult intubations]. PMID- 8470780 TI - Differentiation of Toxoplasma gondii from closely related coccidia by riboprint analysis and a surface antigen gene polymerase chain reaction. AB - The tachyzoite of the human pathogen Toxoplasma gondii is morphologically indistinguishable from the proliferative stages of some other zoonotic coccidia, including Sarcocystis. To determine the identity of such coccidia obtained from human tissues and other sources, we compared riboprints (through restriction enzyme analysis of the polymerase chain reaction [PCR]-amplified small subunit rRNA gene) of the following protozoa: the RH and ts-4 strains of T. gondii, lines OH3 and S11, which are two recently isolated T. gondii-like parasites from Brazil, Neospora caninum, Sarcocystis species, and the malarial parasite Plasmodium berghei. In addition, the protozoan genomes were examined by PCR for homologs of surface antigen genes of T. gondii, and by Southern hybridization to the heterologous rRNA gene probe pSM 389. Strains OH3, S11, ts-4, and RH shared identical riboprints, and OH3, S11, and ts-4 have p22 and p30 surface antigen gene structures similar to RH. In contrast, riboprints for N. caninum and T. gondii differ with respect to Dde 1 sites, and moreover, their genomes vary significantly from one another at both the p22 and p30 gene loci. The riboprints of Sarcocystis and P. berghei differ markedly from T. gondii and N. caninum and from each other. Bam HI pSM 389 restriction fragment length polymorphisms differentiate ts-4 from RH, OH3, and S11. Our results confirm that OH3 and S11 are indeed T. gondii, but that N. caninum and T. gondii are likely to be separate species, thereby resolving previous uncertainties concerning the identity of these parasites. Together, the variation in riboprints and surface antigen gene structure reflects the phylogenetic diversity among these coccidia, and in addition, confirms the value of riboprinting in the identification of apicomplexan parasites such as T. gondii. PMID- 8470782 TI - [A modified Macintosh blade for difficult intubation. The mirror blade]. AB - Difficult intubations can occur in cases of anatomical or physiological abnormalities of the face and neck. They are frequently predictable when specific signs are evident preoperatively. There are still occasional unexpected difficulties during conventional laryngoscopy when common blades like the Macintosh and Foregger types are used. During the past 5 decades several authors have proposed many types of laryngoscopes and blades differing in length and shape, as well as various accessories such as guide-wires, prisms, and mirrors. METHOD. We modified a size 3 Macintosh blade by adding a mirror placed tangential to the external curve near the apex. This configuration allows both conventional direct visualisation of the vocal cords and non-direct viewing through the mirror. Insertion of the tube is facilitated using a specially shaped guide-wire. RESULTS. This equipment was used for orotracheal intubation in 20 patients with different degrees of direct laryngeal visibility prior to otolaryngologic endoscopy and surgery under general anaesthesia. Both methods of larynx visualisation were performed and compared. In 1 patient the mirror was not useful because it became fogged. In all the others we could avoid this problem by warming the blade in water. Only in 1 other case was the conventional view better and intubation seemed to be easier than when the mirror was used. In 15 patients the vocal cords were visualised better with the mirror, and intubation was performed by means of the guide-wire with the non-direct technique. In 2 of these cases difficult direct laryngoscopy of grades 3 and 4 according to the Cormack and Lehane classification was found. Four patients were difficult to intubate and neither type of laryngoscopy was ideal. It is notable that a satisfactory view was achieved in the mirror with much less effort. In particular, there was no need to introduce the blade as deeply or raise its apex as much as is usually done. CONCLUSION. The mirror-blade is a suitable device for management of unexpected difficult intubations. Because of its dual availability, it offers both direct and non-direct visualisation of the larynx. Handling of this mirror blade can be practised extensively, which allows integration of this equipment in the "failed intubation drill". This should be an integral part of the teaching and training of anaesthesia personnel. PMID- 8470783 TI - [General anesthesia in two patients with mitochondrial myopathy]. AB - Two patients with mitochondrial myopathy (Kearns-Sayre syndrome) received general anaesthesia. In the first case propofol-alfentanil anaesthesia was carried out; the second patient received propofol-fentanyl anaesthesia. Muscle relaxation was provided with vecuronium. In both cases we observed a short episode of bradycardia (heart rate < 50.min-1), which was successfully treated with atropine. After the propofol infusion had been stopped, both patients rapidly gained consciousness and were extubated after prompt spontaneous ventilation had returned. Reversal of neuromuscular blockade in the second patient was achieved within 5 min by neostigmine. Special anaesthetic problems in patients with mitochondrial myopathies such as myocardial conduction disturbances, postoperative muscle hypotonia, and possible increased susceptibility to malignant hyperthermia can be overcome by the described anaesthetic management. PMID- 8470784 TI - [Comments on the paper by R. Fretschner et al. Capnometry in pediatric anesthesia]. PMID- 8470785 TI - [Comments on the paper by H.-J Hartung and Th. Luiz. Total spinal anesthesia]. PMID- 8470786 TI - [The stellate ganglion blockade]. AB - Stellate ganglion block is a selective sympathetic blockade affecting one side of the head and neck, and the upper extremity and upper part of the thorax on the same side. It is an important method of treating impaired vascular circulation, sympathetic reflex dystrophy, causalgia and herpes zoster in the area other indications, e.g. acute hearing loss and retinal arterial spasms, are still disputed. The anatomy of the cervical sympathetic chain, the technique used to achieve the block (paratracheal access) and tests of the effectiveness of stellate ganglion blockade are described. The side-effects and complications of the method and other means of sympathetic blockade are discussed. Patients need to be informed of the possible complications and the alternatives available before being asked to give informed consent. PMID- 8470787 TI - [Acute thromboembolism of the lung. Clinical picture--pathophysiology--diagnosis- therapy]. AB - Pulmonary embolism must often be considered as a differential diagnosis, especially in the perioperative period. Only prompt therapeutic measures can reduce the high early mortality in the acute phase of this condition. Diagnostic and therapeutic measures are dependent on the severity of the symptoms. If pulmonary embolism is suspected, heparin is administered. In the case of cardiovascular deterioration, other measures have to be taken. Following confirmation of the diagnosis of pulmonary embolism, several thrombolytic regimens are applicable. Low-dose urokinase (bolus 250,000 U followed by 60,000 80,000 U/h) is associated with a relatively low incidence of bleeding complications. A more rapid reduction of the right ventricular afterload will be achieved via short-term thrombolysis. Newer findings suggest that bolus thrombolysis with 3 million U urokinase is as effective as 100 mg tissue plasminogen activator (rt-PA) administered over a 2-h period. When the patient is found to be in a state of shock, confirmation of the diagnosis has to be delayed. Recommendations include the bolus application of 1.5-3 million U urokinase when right ventricular decompensation is prominent or during cardiopulmonary resuscitation. In case of existing contraindications or postoperatively, low-dose urokinase treatment (bolus 250,000 U followed by 40,000-60,000 U/h, rarely up to 2,200 U/kg per hour) may be initiated when the situation is urgent and there are no treatment alternatives. Bolus application of 1-2 million U urokinase should be considered depending on the severity of the symptoms and the underlying disease. In some hospitals, alternative treatment modalities include catheter-assisted procedures with subsequent local thrombolysis and surgical embolectomy. Pathophysiological aspects as well as therapeutic options in the intensive care unit are discussed in depth. In addition to adequate oxygenation, right ventricular coronary perfusion and contractility may be maintained using various catecholamine infusions. The importance of phosphodiesterase inhibitors, mediator antagonists such as acetylsalicylic acid or ketanserin, and dilators of the pulmonary vascular bed are discussed. PMID- 8470788 TI - [Induction of anesthesia using the new intravenous steroid anesthetic eltanolone (pregnanolone). Dose determination and pharmacodynamics]. AB - Since the 1940s several preclinical investigations have demonstrated the anaesthetic activity of a series of structurally related pregnanes without notable endocrine action. One of the most active of these is pregnanolone (3 alpha-hydroxy-5-beta-pregnane-20-one), which is a naturally occurring metabolite of progesterone. Pregnanolone is not soluble in water, which has prevented its use for clinical research. In 1987, however, a stable oil-in-water emulsion of eltanolone that could be used for i.v. administration in man was introduced by KABI Pharmacia, Stockholm, Sweden. METHODS. In an open study the dose of eltanolone that induces anaesthesia in 50% of the patients (AD50) was estimated according to the "up and down method" of Dixon and Massey. Respiratory and cardiovascular effects were evaluated as well as the reliability of eltanolone emulsion. The study was conducted in accordance with the Declaration of Helsinki and started after the approval of the local Medical Ethics Review Committee. In all, 31 patients of ASA risk categories I and II (male or female with non child bearing potential) were included in the study after written informed consent had been obtained. All patients were premedicated with 5 mg midazolam i.m. about 30 min before the injection of eltanolone. Eltanolone emulsion was given i.v., usually on the back of the hand, over 20 s. In connection with the injection of eltanolone every patient was asked whether he or she felt any pain or discomfort at the injection site. As suggested by results in volunteers in a previous study the starting dose was 0.5 mg/kg body weight. Cessation of counting and loss of eyelash reflex were used as indicators of efficacy in the induction of anaesthesia. If these criteria were achieved within 120 s after the start of injection (responder) the dose for the next patient was decreased by 15%, if not (non-responder), the next patient received the same dose plus 15% (up to 1.01 mg/kg body weight). Heart rate and oxygen saturation were recorded continuously (Sirecust 404; Nellcor) from 1 min before to 10 min after the start of injection, and blood pressure was measured noninvasively 1 min before induction and then at 1, 2, 3, 5, 8 and 10 min from the start of the eltanolone injection (Sirecust 888). If oxygen saturation fell to 85% oxygen was applied by way of the face mask and the patients were ventilated if necessary. Respiratory disturbances, time to and duration of apnoea were recorded, as were involuntary movements or increase in muscle tone. Usually intubation was carried out at the end of the 10-min observation period using thiopentone, vecuronium and suxamethonium. If a patient did not fall asleep or awoke prematurely, intubation was performed in the same way and from this point pharmacodynamic parameters were no longer evaluated for the study. RESULTS. The AD50 was 0.33 mg/kg body weight, and the 95% confidence interval, 0.30-0.36 mg/kg body weight. The eltanolone dose varied from 0.25 to 0.5 mg/kg body weight. Induction was successful in 17 (of 31) patients according to the eyelash reflex as criterion and in 28 according to cessation of counting. Above 0.38 mg/kg body weight efficacy variables were achieved in all patients, while below 0.29 mg/kg body weight eyelash reflex was not lost in any patient. The mean time to loss of consciousness (cessation of counting) in the responder group was 48 +/- 12 s after the start of injection and loss of eyelash reflex was recorded after 94 +/- 13 s. In the nonresponder group eyelash reflex persisted over 120 s in all patients and counting stopped on average after 72 +/- 23 s. Three patients in this group also did not stop counting (dose: 0.29 mg/kg body weight). Blood pressure remained stable in all patients but 1 throughout the observation period. In 1 patient there was an alarming rise in blood pressure from 160/90 mmHg before to 200/100 mmHg 3 min after the injection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8470789 TI - [Quality of induction and adrenocortical function. A clinical comparison of Etomidate-Lipuro and Hypnomidate]. AB - The purpose of this study was to compare etomidate in a lipid emulsion (Etomidat Lipuro; Braun, Melsungen) and in propylene glycol (Hypnomidate, Janssen Pharmaceutica) in 90 patients in terms of anaesthetic induction characteristics with special reference to injection side effects, haemodynamic changes, and quality of induction. Adrenocortical hormones were determined in 30 patients who received either Etomidat-Lipuro, Hypnomidate, or propofol (Diprivan, ICI Pharma) for induction of anaesthesia. METHODS: One hundred twenty patients gave their informed consent to the study. In the first part, 90 patients were assigned at random to two groups in which induction of anaesthesia was performed either with Etomidat-Lipuro or Hypnomidate. Anaesthesia was started by i.v. injection of 25 micrograms/kg alfentanil (Rapifen, Janssen Pharmaceutica). One minute later, the hypnotic agent was injected into a freely running i.v. line (18 Gcannula) that was used only for the hypnotic and was removed 15 min later. During injection, the patients were asked to inform the anaesthesiologist spontaneously and on request about their sensations at the injection site. The time from the beginning of anaesthesia until the disappearance of the eyelash reflex was measured. The patients were ventilated and vecuronium was administered to allow good intubation conditions 2-3 min later. For the first 10 min, blood pressure and heart rate were measured every minute. Postoperatively, the same investigator made rounds once a day and examined the injection sites. Signs of pain, redness, swelling, induration, thrombophlebitis, or thrombosis were noted. In the second part of the study, 30 patients were investigated for endocrinological changes after induction of anaesthesia with Etomidat-Lipuro, Hypnomidate, or Diprivan. The patients were allocated to the groups at random. A radial artery catheter was inserted in every patient. Sampling took place 30 min before and 1 and 2 h after induction. Additional samples were drawn 30 min and 1, 2, and 22 h after i.v. administration of 0.25 mg ACTH (Synacthen, Ciba-Geigy). The plasma concentrations of cortisol, 17 alpha-OH-progesterone, and aldosterone and the renin activity were determined by high-performance liquid chromatography. RESULTS: The loss of the eyelash reflex occurred 42.9 +/- 8.7 and 42.2 +/- 11.0 s after the administration of Etomidat-Lipuro and Hypnomidate. The haemodynamic changes were minimal in both groups. After administration of alfentanil, local side effects of the hypnotics were scarce, with a tendency to be weaker and more seldom after Etomidat-Lipuro (3/55 versus 8/55). The postoperative vein reactions were generally mild and occurred in 17 out of 55 patients after Etomidat-Lipuro and 15 out of 55 patients after Hypnomidate. In most cases these signs were no longer present on the 2nd day after the procedure. Cortisol levels were depressed initially by all the hypnotic drugs used. While there was spontaneous recovery in the Diprivan group after 2 h combined with a positive overshooting response to ACTH stimulation, in the etomidate groups cortisol could not be stimulated; it normalized slowly during the following 24 h. The 17 alpha-OH-progesterone increase was significant in the etomidate groups after the administration of ACTH. The aldosterone levels decreased after etomidate injection and had not normalized 24 h later, while there was a normal response to ACTH in the propofol group. There was a normal decrease in renin activity in all three groups after the administration of ACTH. CONCLUSION: Local side effects are minimal after the administration of Etomidat Lipuro and Hypnomidate. Alfentanil reduces the injection pain of etomidate induction agents. Cortisol and aldosterone are depressed by etomidate, but the clinical relevance is minimal after a single bolus injection. PMID- 8470790 TI - [Modified hemoglobin as a blood substitute in a rat model]. AB - The use of modified haemoglobin solutions as blood substitutes has been investigated extensively during the past decades. Ultrapurified, polymerised bovine haemoglobin (upbHb) is a promising new substance in this respect. It was the aim of the present investigation to study the cardiovascular and respiratory effects of massive blood replacement with upbHb in a new model of conscious rats with continuous haemodynamic monitoring. METHODS. The right femoral artery and vein of 13 male Sprague-Dawley rats were catheterised during halothane-N2O-O2 anaesthesia. A thermistor catheter was placed in the descending aorta via the left femoral artery for measuring cardiac output by the thermodilution method. After recovery from anaesthesia blood replacement was achieved by arterial blood withdrawal and simultaneous venous infusion of upbHb in equal amounts. The haematocrit was lowered to < 3% and the animals were then left undisturbed in a rat restrainer while breathing room air. RESULTS. The animals showed no signs of disturbed behaviour patterns, distress, or adverse reactions. There were no significant changes in cardiac index and oxygen delivery during the investigation period of 4 h. A marked increase in mean arterial pressure (MABP) and systemic vascular resistance (SVR) of 30% was observed while stroke volume remained unchanged. Blood gases, acid-base status, and plasma glucose showed no major changes. Plasma oncotic pressure increased during the investigation period. CONCLUSIONS. The results indicate that there is adequate oxygenation and sufficient systemic oxygen delivery in conscious and drug-free rats after isovolaemic haemodilution with upbHb to a final haematocrit of < 3%. In contrast to previous haemodilution studies, which have tested non-oxygen-carrying solutions, no changes in cardiac index were observed. The cause of the increase in MAP and SVR remains to be established. PMID- 8470791 TI - [Longitudinal distribution of pulmonary vascular resistance in patients with acute respiratory insufficiency]. AB - Effective pulmonary capillary pressure (Pc) is a major factor determining transvascular fluid filtration in the lung. It may easily be estimated from the pressure decay after rapid pulmonary artery occlusion. If Pc is known, the longitudinal distribution of pulmonary vascular resistance (PVR) can be evaluated. The present study was performed to address the following questions: (a) whether the severity of acute lung injury influences Pc and the longitudinal distribution of PVR; and (b) whether pulmonary artery occlusion (PAOP) or wedge pressure represents effective Pc during acute respiratory failure. PATIENTS AND METHODS. The investigation was performed in 45 mechanically ventilated patients. According to Murray's criteria 13 patients showed no lung injury, 19 had mild to moderate lung injury, and 13 had severe lung injury (adult respiratory distress syndrome, ARDS). As described by Holloway, effective Pc was evaluated from the pressure decay after rapid occlusion of the pulmonary artery (Figs. 1 and 2). The precapillary pressure gradient was determined as the difference between mean pulmonary artery pressure and Pc, the postcapillary pressure gradient as the difference between Pc and PAOP. Three measurements were performed and Pc determined as their mean value. The Kruskal-Wallis test and Mann-Whitney U test were performed to check statistically significant differences between groups. A Bonferroni correction was performed for multiple testing; P < 0.05 was accepted. RESULTS. Effective Pc was significantly different between patients with severe lung injury (20 +/- 3 mm Hg) and patients with mild to moderate lung injury (16 +/- 3 mm Hg), and between the latter group and patients without lung injury (12 +/- 3 mm Hg). The postcapillary pressure gradient and the relative amount of pulmonary venous vascular resistance, as well, were significantly influenced by the severity of the lung injury. In patients with ARDS the postcapillary pressure gradient was 4 +/- 1 mm Hg, whereas in patients with mild to moderate and without lung injury the postcapillary pressure gradients were 3 +/- 1 mm Hg and 2 +/- 1 mm Hg, respectively. Two ARDS patients had a postcapillary pressure gradient of 7 mm Hg (Pc 22 mm Hg and 19 mm Hg, PAOP 15 mm Hg and 12 mm Hg). One patient with severe lung injury had a postcapillary pressure gradient of 9 mm Hg (Pc 22 mm Hg, PAOP 13 mm Hg). In patients with severe lung injury 28 +/- 7% of the PVR was located in the postcapillary vascular system, whereas in patients with mild to moderate and without lung injury 22 +/- 7% and 16 +/- 6% of PVR was located in the pulmonary venous system. CONCLUSIONS. The longitudinal distribution of PVR is influenced by the severity of lung injury. PAOP, therefore, may not represent changes in Pc in patients with acute respiratory failure. The routine use of Pc measurement, however, can not be recommended until it has proven more useful than determination of PAOP when managing critically ill patients. PMID- 8470792 TI - Dynamic fluorescence measurements of two-state systems: applications to calcium chelating probes. AB - A fluorescence technique for characterizing ligand binding is evaluated. This technique uses the combination of steady-state and time-resolved methods to recover molar concentrations and overcomes errors inherent in the use of either method alone. The technique is applicable to time-resolved measurements made either with time-domain or frequency-domain instrumentation. A straightforward single-frequency phase/modulation approach is presented to determine whether an experimental system can be described by a two-state system. The approach is based on a nonlinear transformation of the phase/modulation data that results in a linear model function. Here, the theory is applied to the fluorescent calcium binding probes Quin-2 and Calcium Green, but is relevant to studies involving other interacting systems. The technique described is used to assess the fraction of bound ligand (Ca2+) and binding constants for these probes. PMID- 8470793 TI - Detection and quantitation of heme-containing proteins by chemiluminescence. AB - A commercial assay for chemiluminescence (CL) has recently been developed for visualizing horseradish peroxidase-conjugated probes for antibodies and nucleic acids. To assess the utility of CL for detecting the peroxidase activity of other heme-containing proteins, the sensitivity of CL and a standard chromogenic stain for visualizing heme-proteins in SDS-polyacrylamide electrophoretic gels were compared. The ability of these systems to visualize heme-proteins on electroblots and dot blots was also examined. The chromogenic stain, which uses 3,3',5,5' tetramethylbenzidine for a dye, and CL had equal sensitivity in electrophoretic gels. Both assays were affected by 2-mercaptoethanol in the solubilization buffer. In blotting assays, CL was 10- to 10,000-fold more sensitive for detecting samples including cytochrome C and blood. Quantities of protein requiring 18 h to detect by staining were visualized in minutes by CL. Scintillation spectroscopy of CL emitted by blood, urine containing supplemental blood, or urine from a patient with hematuria resulted in a linear relationship between peroxidase activity and concentration, allowing for quantitation of blood over a broad range of concentrations. These results indicate that CL can rapidly detect and quantitate heme-proteins and may facilitate both basic studies of heme proteins and clinical and forensic analyses of blood. PMID- 8470794 TI - High resolution polyacrylamide gel electrophoresis of Physarum polycephalum histones: improved resolution of variants and modified forms. AB - An electrophoresis system providing a good resolution of all basic proteins and their variants or modified forms extracted from Physarum polycephalum nuclei was developed. This two-dimensional polyacrylamide gel electrophoresis system combines the use of an AUT gel containing a preformed gradient of urea in the first dimension and a SDS polyacrylamide gel in the second one. PMID- 8470795 TI - On the activities of Escherichia coli exonuclease III. AB - Exonuclease III (Exo III) of Escherichia coli is a DNA-modifying enzyme very frequently used in molecular biology. The experiments described here were carried out with the aims of reliably controlling exonuclease activity and of learning more about the enzyme's specificities. The dependence of Exo III activity on factors such as temperature (including heat inactivation), the concentrations of Exo III and NaCl, and the concentration and shape of 3' termini was investigated. Double stranded DNA was found to be a competitive inhibitor of the enzyme activity. Some four nucleotide 3' protrusions were shown to be sensitive to Exo III digestion. The synchronism of deletion was also examined. Implications for the proposed mechanism of activity are discussed. PMID- 8470796 TI - Surface-enhanced Raman spectroscopic detection of CO2-(3), SO2-(3), and nucleic acid bases using polyvinyl alcohol film doped with Ag fine particles. AB - Surface-enhanced Raman scattering (SERS)-active polyvinyl alcohol films doped with Ag particles have been prepared by a counterdiffusion method. SERS spectra of CO2-(3), SO2-(3), and DNA bases have been observed by using the films. The films containing aggregated Ag particles are useful to observe SERS spectra of adsorbates. DNA bases (cytosine, uracil, thymine, guanine, and adenine) can be detected at a level of 10(-8)-10(-9) M by this method. PMID- 8470797 TI - A fast and sensitive method for detection of phospholipid-binding proteins on nitrocellulose membranes. AB - We describe a sensitive new method for specific detection and quantitation of phospholipid-binding proteins using two purified lipocortins as model proteins. The method consists of blotting proteins to nitrocellulose membranes followed by incubation with radiolabeled phospholipids and autoradiographic detection of bound phospholipids. It allows specific detection of phospholipid binding proteins to a threshold of about 100 ng/spot and their quantitation up to several micrograms as well as rapid analysis of specific phospholipid binding properties of individual proteins. If performed as a dot-blotting technique, the method permits the simultaneous analysis of a large number of samples and the establishment of Ca2+ and phospholipid binding curves. If blotting is preceded by electrophoresis, the method also allows specific detection and quantitative estimation of phospholipid binding proteins in crude biological preparations and may thus be useful for monitoring and analysis of these proteins in various biological samples. PMID- 8470798 TI - Glucose metabolism in mammalian cells as determined by mass isotopomer analysis. AB - A method using 13C isotopes and GCMS/SIM was developed and was used to study glucose metabolism in several mammalian cell lines. Using [U-13C6]glucose, the 13C isotopomer distributions in glucose, lactic acid, glutamic acid, aspartic acid, and gamma-aminobutyric acid produced by the cells were determined, and glycolysis, gluconeogenesis, and the flux into the amino acid pools were calculated. A 1:1 mixture of [U-13C6]glucose and [1-13C]glucose was used to examine the loss of 1-13C carbon from [1-13C]glucose via the pentose monophosphate pathway in the cells; this new method measures the production of [3 13C]lactic acid and [U-13C3]lactic acid, and thus avoids most systematic errors that result from the endogenous production of 12C-lactic acid during metabolic conversion; in addition, glycolysis and the recycling of glucose and lactic acid can be examined at the same time. The mass isotopomer analysis method is reproducible and sensitive, and can be used to analyze metabolites in 10(-7) M concentration with less than 10(5) cultured human cells. This method was used to examine metabolic regulation of glucose in fibroblasts, lymphoblasts, and PC12 cells under various conditions of metabolic disturbance. The method appears to have wide applicability for the study of metabolic regulation of glucose and metabolic defects in cells. PMID- 8470799 TI - Synthesis of 3,4-cis-[3H]leucocyanidin and enzymatic reduction to catechin. AB - A novel method is presented for the synthesis and purification of (+)-2,3-trans 3,4-cis-[4-3H]leucocyanidin. Soluble enzyme extracts from developing barley grains and leaves of the forage legume Onobrychis viciifolia (sainfoin) catalyzed the NAD(P)H-dependent reduction of (+)-2,3-trans-3,4-cis-[4-3H]leucocyanidin to (+)-[4-3H]catechin. NADPH was the preferred substrate. With extracts of barley the rate of reaction with 1 mM NADH was 20% of the rate found with NADPH. With extracts from both tissues there was a broad pH optimum around pH 6.6. PMID- 8470800 TI - A highly sensitive and fast nonradioactive method for detection of polymerase chain reaction products. AB - A novel system for the detection of polymerase chain reaction (PCR) products has been developed. The system is based on a PCR in which one of the primers is biotinylated and digoxigenin-11-dUTP is incorporated during elongation. Biotinylated PCR products are captured on streptavidin-coated solid supports, and alkaline phosphatase conjugated to anti-digoxigenin antibody is subsequently bound to the incorporated digoxigenin. The detection may be obtained with colorimetric, fluorescent, or luminescent substrates for alkaline phosphatase. The detection system can be performed in microtiter plates allowing easy handling of multiple samples. The total assay time following the PCR is between 1 and 2 h dependent on the type of substrate and the type of solid support applied in the system. Within this period of time the system is capable of detecting 1 template in 29 cycles of PCR. PMID- 8470801 TI - Dimethyl sulfoxide-mediated primer Tm reduction: a method for analyzing the role of renaturation temperature in the polymerase chain reaction. AB - We report a method for optimizing the specificity of product formation in the polymerase chain reaction (PCR). This technique is based on the use of dimethyl sulfoxide (DMSO) and takes into account primer Tm. The reduction in Tm by DMSO is directly correlated with renaturation temperature such that a DMSO gradient reflects a temperature gradient. We use this relationship to show that optimum product formation usually occurs at or within several degrees of the midpoint Tm of a given primer pair. We illustrate these correlations using three examples deriving PCR products from a human cDNA library, representing the casein kinase II alpha and beta subunits as well as the 5' untranslated region for the beta subunit. By following product formation as a function of renaturation temperature, we postulate rules for cycle design based on primer Tm. Implications for the use of degenerate primers are discussed. PMID- 8470802 TI - Radiolabeled biotinyl peptides as useful reagents for the study of proteolytic enzymes. AB - A radiometric assay for studying the proteolytic activity of endopeptidases using a radiolabeled biotinyl peptide substrate is described. The method relies on the use of a peptidyl substrate incorporating susceptible bonds located between a biotinyl group at one end and a radioiodinated group at the other end. Two tyrosine-containing peptidyl substrates, a fragment of rat plasma kallikrein and a derivative of Leu-enkephalin, were coupled to biotin by reacting with N hydroxysuccinimidyl-6-(biotinamido) hexanoate. The enzymatic activity is measured by the release into solution of the radiolabeled peptide fragment following selective retrieval, using immobilized avidin, of the biotinyl undigested substrate and the unlabeled biotinyl peptide fragment. This study illustrates that retrieval can be done either before incubation with the enzyme by immobilizing the labeled substrate onto avidin-agarose or, alternatively, after incubation by treating the resulting digest with immobilized avidin. The identity of the labeled released peptides and hence the sites of cleavage can be obtained following separation by RP-HPLC. This assay, in addition to allowing proteolysis to occur with the substrate either in solution or immobilized, is rapid, sensitive (less than 1 pg/ml of trypsin), reproducible, and applicable to the detection of members of all endopeptidase classes. Furthermore, incubation of the radiolabeled biotinyl peptide substrates with enzymes immobilized within polyacrylamide gel slices can be used to detect proteolytic activity following electrophoretic separations under denaturing or nondenaturing conditions. PMID- 8470803 TI - Electrophoresis of neurochordins, a family of high molecular weight neural tissue glycoproteins, on horizontal submerged agarose gels in the presence of dodecyl sulfate. AB - We have developed a procedure for the use of agarose gels to separate electrophoretically neurochordins, a family of high molecular weight neural tissue glycoproteins. This procedure is a modification of the method of horizontal submerged electrophoresis on agarose gels routinely applied for the separation of DNA restrictions. For protein analysis we prepared gels of higher agarose concentration (3%), and 0.1% of sodium dodecyl sulfate was present in the buffer used both for gel formation and as an electrode buffer. After electrophoresis agarose gels can be directly stained with Coomassie blue, or proteins can be transferred from the gel to nitrocellulose or nylon filters for immunostaining. The main advantage of the proposed method compared to the method of electrophoresis on large-pore, composite agarose/polyacrylamide gels is its simplicity. Other proteins of very high molecular weight can also be successfully separated by this technique. PMID- 8470804 TI - Evidence for telluroamino acid in biological materials and some rules of assimilation of inorganic tellurium by yeast. AB - A natural substance, telluroamino acid, was discovered in tellurium yeast by GC and GC/MS. This substance was obtained for the first time by means of the assimilation of inorganic tellurium by yeast, having 600 ppm of total Te and 150 ppm of telluroamino acid. Some rules for such an assimilation were found: the content of total Te and telluroamino acid in tellurium-yeast is closely related to the kind of culture media used and is proportional to the concentration of Te in culture media. This discovery is of theoretical and practical significance, especially for the production by a simpler microbiological synthesis of rare and expensive organic tellurium compounds which hopefully will prove to be anticarcinogens like the selenium-yeast, and for explaining the biochemical effect of tellurium on the human body. PMID- 8470805 TI - A colorimetric assay for penicillin-V amidase. AB - The hydrolysis of penicillin-V to phenoxyacetic acid and 6-aminopenicillanic acid by the fungal enzyme penicillin-V amidase is of industrial importance since the 6 aminopenicillanic acid produced is an intermediate for semisynthetic penicillins. A rapid colorimetric assay of penicillin-V amidase was developed which uses 2 nitro-5-(phenoxyacetamido)-benzoic acid as a substrate. The released chromophore, 2-amino-5-nitrobenzoic acid, was detected at 405 nm. Using penicillin-V amidase from the fungus Fusarium oxysporum, the KM and Vmax for this substrate were 0.89 mM and 2.6 mumol/min/mg enzyme, respectively. Hydrolysis could be competitively inhibited by penicillin-V with a Ki of 4 mM. The change in the initial velocity of hydrolysis of 2-nitro-5-(phenoxyacetamido)-benzoic acid at 500 microM was linear over the range of 0.5 to 10 micrograms/ml enzyme. These results show that this new compound is useful in determining the presence and levels of penicillin V amidase. PMID- 8470806 TI - A refinement of the Akabayashi-Saito-Kato modification of the enzymatic methods for 2-deoxyglucose and 2-deoxyglucose 6-phosphate. AB - Akabayashi et al. made a valuable modification of the enzymatic methods from our laboratory for measuring 2-deoxyglucose and 2-deoxyglucose 6-phosphate. Their modified procedure eliminates glucose and glucose 6-phosphate by conversion to fructose-1,6-bisphosphate, thereby saving two analytical steps. However, the present report describes a limitation of this new elimination procedure which is due to its unexpected reversibility, and provides an easy way to circumvent this limitation, namely heating to destroy the reagent enzymes before proceeding. The final result is a more flexible analytical scheme that is capable of measuring 2 deoxyglucose and its phosphate down to extremely low levels in the presence of up to thousandfold higher glucose concentrations. The completeness of glucose elimination eliminates both the problem of contamination of available glucose-6 phosphate dehydrogenases with 6-phosphogluconate dehydrogenase, and also the effect of the presence in this same enzyme of a trace of glucose dehydrogenase activity, which is an apparent side reaction. PMID- 8470807 TI - High-performance liquid chromatography separation and quantitation of methylprednisolone from rat brain. AB - A sensitive, reliable method for the extraction, separation, and quantitation of methylprednisolone from rat brain is reported. The method can accurately quantitate methylprednisolone levels between 9.8 and 2500 ng/injection using a two-step HPLC separation and monitoring absorbance at 254 nm. A 90% extraction recovery of methylprednisolone (interday variation of 9.0% and an intraday variation of 0.0 to 7.7%) from rat cortex was obtained with a double extraction method using low toxicity solvents. These solvents are known to quantitatively extract the neutral lipids and phospholipids from brain. Combined with the ability to separate the neutral lipid and methylprednisolone fractions for further separation, and the ability to separate all phospholipid classes in the first run, this method offers great utility combined with the reliable, high extraction recovery and sensitive quantitation of methylprednisolone. PMID- 8470808 TI - Measurement of intracellular calcium using bioluminescent aequorin expressed in human cells. AB - Changes in intracellular free calcium concentration ([Ca2+]i) are involved in many important physiological responses. Detecting changes in [Ca2+]i is crucial to understanding the physiologic roles of intracellular free calcium. We have characterized changes of [Ca2+]i in human cells transfected with apoaequorin cDNA. When reconstituted in vivo by incubating transfected cells with coelenterazine, aequorin emits light upon binding free calcium and acts as a bioluminescent indicator for calcium. We have used this system to determine the concentration response relationship of serotonin for its receptor. Cells cotransfected with serotonin receptor cDNA and apoaequorin cDNA emitted light upon treatment with serotonin. The light emission responses were saturable and serotonin concentration-dependent, and they were inhibited by serotonin antagonists. Human 293 cells that stably express apoaequorin have been created. This system should facilitate the investigation of [Ca2+]i involvement in physiological and pathophysiological responses. PMID- 8470809 TI - Protein kinase assay using tritiated peptide substrates and ferric adsorbent paper for phosphopeptide binding. AB - The recently described synthesis of ferric adsorbent paper has made possible the modification of protein kinase assays. The adsorbent contains ferric chelate groups, which are responsible for the binding of phosphopeptide via phosphate group. The selective adsorption of phosphopeptide contra nonphosphorylated peptide allows the use of tritium-labeled peptides and unlabeled ATP as substrates. The binding of the reaction product to the adsorbent was complete and was not affected by the amino acid sequence of the peptide. The conditions required for the separation of the produced phosphopeptide from the initial peptide have been worked out as well. The firmly bound phosphopeptide should be released from the ferric adsorbent paper prior to liquid scintillation counting. Using 0.1 m NH4HCO3 solution (pH 8.0), the elution of phosphopeptides was almost complete. The modified protein kinase assay proposed herein is rapid and allows handling of multiple samples simultaneously. In addition, the ferric paper method avoids the use of 32P-isotope, replacing it with 3H which has lower radiation energy and a much longer half-life. PMID- 8470810 TI - Kinetic silver staining and quantification of proteins adsorbed to microtiter plates. AB - A silver stain was used to detect and quantitate proteins adsorbed to microtiter plate wells. The kinetics of the development of the silver stain were analyzed with an automated microtiter plate reader. The lag time for stain development was found to be a consistent indicator of the amount of protein adsorbed to a microtiter plate well. Protein which was not preadsorbed to the microtiter plate was not effectively stained by silver. Complete adsorption of protein applied to the microtiter plate was possible by drying small amounts of protein in very dilute buffers. Variations in sensitivity for different proteins were less than 30% for the panel of proteins examined. Determinations from kinetic silver staining agreed with those from copper staining for bovine albumin adsorbed to microtiter plates. The precision of kinetic silver staining assay was optimal in the range of 40 to 200 ng per microtiter plate well. In this range, the standard deviations averaged less than 5%. Even smaller amounts of protein can be detected and interpolated down to approximately 10 ng per well. The kinetic silver staining method can be used on standard microtiter plate readers without special filters and is readily adaptable to automated systems. PMID- 8470811 TI - A critical assessment of the RNAse protection assay as a means of determining exon sizes. AB - The RNAse protection assay is a highly sensitive assay which is commonly used to detect specific hybridization between complementary RNAs and to determine exon sizes in gene characterization studies. Unfortunately, each of the numerous steps involved in the assay could give artifacts depending on the probe used. In this study, common causes of artifacts have been identified using riboprobes which identify exons of known sizes. The RNAse concentration and duration of digestion used were found to be critical factors affecting exon size estimations. Five different riboprobes were tested to obtain a consensus optimum RNAse condition- 10 micrograms/ml RNAse A, 0.5 microgram/ml RNAse T1--enabling the correct determination of exon sizes. This condition was further analyzed for its specificity when RNAse protection assays were performed between highly homologous RNA fragments from two different species. Results show that this concentration of RNAse would efficiently cleave a minimum of two nucleotide mismatches. Single nucleotide mismatches were frequently not cleaved by the same RNAse concentration making it possible to detect the correct exon size regardless of such sequence polymorphisms in gene sequences. PMID- 8470812 TI - Anion-exchange analysis of ribulose-bisphosphate carboxylase/oxygenase reactions: CO2/O2 specificity determination and identification of side products. AB - An improved anion-exchange chromatographic method for determining the carboxylation/oxygenation specificity (tau) of ribulose 1,5-bisphosphate carboxylase/oxygenase is presented. This assay, which entails radiometric detection of [1-3H]ribulose-bisphosphate turnover products separated on MonoQ anion-exchange resin, is more convenient, less error-prone, and more generally applicable than previous methods of tau determination. It is suitable for both wild-type and site-directed mutant enzymes of widely varying activity and specificity levels and allows simultaneous visualization of various side products of ribulose-bisphosphate processing. A facile method for scrubbing dissolved O2 from carboxylase reaction solutions, which does not require extensive purging and exchange of dissolved gases, is also described. PMID- 8470813 TI - Versatile avian retrovirus vectors. PMID- 8470814 TI - Instantaneous blocking for immunoblots. PMID- 8470815 TI - A pH-independent assay for pectin methyl esterase for use in column chromatography. PMID- 8470816 TI - Protein molecular weight determinations by MALD mass spectrometry: a superior alternative to gel filtration. PMID- 8470817 TI - Molecular dosimetry. PMID- 8470818 TI - Detection of liquid injection using an atmospheric pressure ionization radiofrequency plasma source. AB - An atmospheric pressure rf plasma source which operates in a variety of different buffer gases has been developed as an ionization method for organic samples introduced by liquid injection into atmospheric pressure ionization mass spectrometry (API/MS). The rf source can operate in He at < 1 W of load power at 165 kHz. It can also be sustained in Ar, N2, air, and CO2 at a load power of < 15 W. In most cases studied, the protonated molecule, MH+, is observed with little or no fragmentation even under the relatively high current conditions of the discharge. However, using increasingly higher acceleration voltages between the skimmers in the differentially pumped region between atmospheric pressure and high vacuum, one can induce fragmentation via collision-induced dissociation. This can be assisted in these experiments via the use of a heavy buffer gas. The detection limits achieved for rf/API plasma detection are typically in the low femtomole region for small organic molecules including neurotransmitters, PTH amino acids, steroids, drugs, pesticides, and explosives. The detection can be performed with quantitation over at least 4 orders of magnitude. PMID- 8470819 TI - Collisional fragmentation of glycopeptides by electrospray ionization LC/MS and LC/MS/MS: methods for selective detection of glycopeptides in protein digests. AB - Mass spectrometric methods of glycopeptide-specific detection in liquid chromatography/electrospray mass spectrometry (LC/ESMS) of glycoprotein digests are explored using a variety of glycopeptide models and then applied to soluble complement receptor type I, a 240-kDa glycoprotein containing 25 potential sites of N-glycosylation. The most specific method, requiring a triple quadrupole, involves monitoring of sugar oxonium fragment ions during precursor-ion scan ESMS/MS. Signals derived from nonglycosylated peptides are virtually eliminated, resulting in a total-ion current chromatographic trace of only the glycopeptides present in the digest. The corresponding mass spectra yield molecular weight and glycopeptide microheterogeneity information. An alternative and complementary approach that we term collisional-excitation scanning also involves fragmentation of glycopeptides to sugar oxonium ion fragments but does not involve any mass selection process, permitting the experiment to be performed on a single quadrupole instrument. The resulting total ion chromatogram is similar to the UV chromatogram (215 nm), but a selected-ion chromatogram for carbohydrate-specific ions such as the N-acetylhexosamine oxonium ion (m/z 204) produces a glycopeptide specific trace. Although there can sometimes be peptide interferences in the spectra of the indicated glycopeptide-containing chromatographic peaks, this latter approach permits peptide mapping to be performed on the same data set that also indicates the location of glycopeptides in the chromatogram. Both methods are suitable for detection of glycopeptides with all common classes of oligosaccharides in either N- or O-linkage to the peptide. PMID- 8470820 TI - Determination by heteronuclear NMR spectroscopy of the complete structure of the cell wall polysaccharide of Streptococcus sanguis strain K103. AB - Although complete structures of complex polysaccharides have traditionally been determined by chemical degradative methods, a number of recent developments in instrumentation have greatly facilitated this task. We illustrate the application of several of these methods in a determination of the complete covalent structure of the polysaccharide from Streptococcus sanguis K103, which is composed of an octasaccharide repeating subunit linked by phosphodiester bonds. Carbohydrate analysis by HPAE-PAD and by reverse-phase chromatography of benzoylated derivatives of the hydrolysis products of the polysaccharide gave glucose (3 mol), galactose (1 mol), rhamnose (2 mol), N-acetylglucosamine (1 mol), and galactose 6-phosphate (1 mol). Circular dichroism of the O-benzoylated monosaccharides showed the absolute configurations to be D for all residues except for rhamnose, which is L. The 1H NMR spectrum was completely assigned by two-dimensional homonuclear methods (DQF-COSY, NOESY, HOHAHA). The stereochemistry of pyranosides was assigned from 3JHH coupling constant values determined from these experiments. The 13C spectrum was assigned by 1H-detected heteronuclear multiple-quantum correlation (1H[13C] HMQC) and by the hybrid method of HMQC-COSY. The glycosidic linkage positions of the polymer were determined by 1H-detected multiple-bond correlation (1H[13C] HMBC) and by 2D NOESY spectra. The position of the phosphodiester linkage was determined by splitting observed in the 13C resonances due to 31P couplings leading to the overall structure given in Chart I. PMID- 8470821 TI - Expression of neural cell adhesion molecule (NCAM) during the first molar development in the mouse. AB - NCAM, the neural cell adhesion molecule, was immunolocalized in the mandibular first molar tooth germ of the mouse. NCAM was first detected in the tooth germ of the late bud stage, where only the cells in the outer part of the condensed mesenchyme (primitive dental follicle) exhibited faint immunoreactivity. The entire dental follicle was intensely immunostained for NCAM from cap stage to the stage when root formation started. During root formation, NCAM disappeared from the follicular tissue surrounding the cervical root as well as from the part covering the crown top. This loss of NCAM proceeded in the direction of the root apex, but even after the tooth had achieved functional occlusion, NCAM was still expressed by the mesenchymal cells adjacent to the root apex. On the other hand, NCAM was negative in the dental papilla until birth. After birth, NCAM immunoreactivity appeared in the basal portion of the dental papilla, but this NCAM-positive area gradually diminished in width during the root elongation. Instead, another NCAM-positive zone appeared in the core of the pulp during root formation. Even in the tooth that had already erupted, the pulp core contained cells that were strongly positive for NCAM immunostaining. In addition to its expression in the above two mesenchymal cell lineages, NCAM was transiently expressed by epithelial components of the tooth germ, some of the cells of the dental lamina and the enamel organ. The results suggest that NCAM participates in several processes of tooth development. PMID- 8470822 TI - Differentiation of functional hepatocytes and biliary epithelial cells from immature hepatocytes of the fetal mouse in vitro. AB - Differentiation of functional hepatocytes and biliary epithelial cells from immature hepatocytes was analysed in vitro. When fetal mouse liver fragments containing immature hepatocytes but no bile ducts were cultured organotypically, the immature hepatocytes differentiated into large hepatocytes. Some of these expressed bile duct markers such as cytokeratin and Dolichos biflorus agglutinin binding sites, though only to a small extent, and typical intrahepatic bile duct cells failed to differentiate. Dexamethasone stimulated immature hepatocytes to differentiate into both mature hepatocyte and biliary epithelial cell lineages. Especially in the liver fragments cultured on Matrigel, dexamethasone stimulated the expression of bile duct markers (such as cytokeratin and binding sites for two types of lectin) in the immature hepatocytes. These results support the idea that immature hepatocytes can differentiate into both mature hepatocytes and biliary epithelial cells during normal development of the mouse liver, and suggest that glucocorticoids stimulate both these differentiation pathways. It also seems that basal laminar components may play a role in bile duct differentiation. PMID- 8470823 TI - Functional associations between collagen fibre orientation and locomotor strain direction in cortical bone of the equine radius. AB - A novel technique for determining the collagen fibre orientation pattern of cross sections of cortical bone was used to study mid-diaphyseal sections from the equine radius. Several in vivo strain gauge studies have demonstrated that this bone is loaded in bending during locomotion in such a way that the cranial cortex is consistently subjected to longitudinal tensile strains and the caudal cortex to longitudinal compressive strains. Twenty-three radii from 17 horses were studied. All the bones obtained from adult horses exhibited a consistent pattern of collagen fibre orientation across the cortex. The cranial cortex, subjected to intermittent tension, and the lateral and medial cortices, through which the neutral axis passes, contained predominantly longitudinally oriented collagen fibres. The caudal cortex, subjected to longitudinal compression during life, contained predominantly oblique/transverse collagen. This pattern was less evident in bones from foals. Microscopic analysis of the bones studied showed that primary lamellar bone was composed of predominantly longitudinal collagen fibres, irrespective of cortex. However, there was a strong relationship between cortical location and fibre orientation within remodelled bone. Secondary osteons which formed in the caudal (compressive) cortex contained predominantly oblique/transverse collagen, while those which formed elsewhere contained longitudinal collagen. This observation explained the developmental appearance of the characteristic macroscopic pattern of collagen fibre orientation across the whole cortex in the adult. These findings provide evidence for the existence of a relationship between the mechanical function of a bone with its architecture, and now demonstrate that it extends to the molecular level. PMID- 8470824 TI - Mechanical implications of collagen fibre orientation in cortical bone of the equine radius. AB - Mechanical test specimens were prepared from the cranial and caudal cortices of radii from eight horses. These were subjected to destructive tests in either tension or compression. The ultimate stress, elastic modulus and energy absorbed to failure were calculated in either mode of loading. Analysis was performed on the specimens following mechanical testing to determine their density, mineral content, mineral density distribution and histological type. A novel technique was applied to sections from each specimen to quantify the predominant collagen fibre orientation of the bone near the plane of fracture. The collagen map for each bone studied was in agreement with the previously observed pattern of longitudinal orientation in the cranial cortex and more oblique to transverse collagen in the caudal cortex. Bone from the cranial cortex had a significantly higher ultimate tensile stress (UTS) than that from the caudal cortex (160 MPa vs 104 MPa; P < 0.001) though this trend was reversed in compression, the caudal cortex becoming relatively stronger (185 MPa vs 217 MPa; P < 0.01). Bone from the cranial cortex was significantly stiffer than that from the caudal cortex both in tension (22 GPa vs 15 GPa; P < 0.001) and compression (19 GPa vs 15 GPa; P < 0.01). Of all the histo-compositional variables studied, collagen fibre orientation was most closely correlated with mechanical properties, accounting for 71% of variation in ultimate tensile stress and 58% of variation in the elastic modulus. Mineral density and porosity were the only other variables to show any significant correlation with either UTS or elastic modulus. The variations in mechanical properties around the equine radius, which occur in close association with the different collagen fibre orientations, provide maximal safety factors in terms of ultimate stress, yet contribute to greater bending of the bone as it is loaded during locomotion, and thus lower safety factors through the higher strains this engenders. PMID- 8470825 TI - Proliferative activity of the developing seminiferous epithelium during prespermatogenesis in the golden hamster testis measured by bromodeoxyuridine labeling. AB - Bromodeoxyuridine (BrdU)-labeling was used to study the cell kinetics of the developing seminiferous epithelium in the testes of golden hamsters aged 10.5 to 27.5 days post conception (dpc), i.e., during a period beginning one developmental day before testicular differentiation (11.5 dpc) and extending to the appearance of the first "mature" spermatogonia. Supporting (Sertoli) cells continuously proliferate throughout the period studied. Labeling indices amount to about 30% between the 10.5th and 16.5th dpc, and subsequently decrease to levels below 10% on the 26.5th and 27.5th dpc. Germ cells (prespermatogonia) proliferate between the 10.5th and 15.5th dpc and again, after a period of mitotic quiescence, from the 24.5th dpc onwards. This pattern of prespermatogonial proliferation substantiates and further specifies the successive appearance of M-prespermatogonia (10.5th to 15.5th dpc: proliferating), T1-prespermatogonia (16.5th to 23.5th dpc: quiescent), and T2 prespermatogonia (24.5th to 27.5th dpc: proliferating). Thus, the M prespermatogonial phase of germ cell proliferation is shown to commence at least 24 h before testicular differentiation. Transitions from M- to T1-phase and from T1- to T2-phase are rather abrupt. Both the latter observation and the comparison with oogonial development in the female at the corresponding time (onset of meiosis) indicate the presence of an underlying control mechanism operative during prespermatogenic development. Due to different nuclear staining patterns, the BrdU-labeling method allows temporal subdivision of the S-phase, thus opening up prospects of more detailed cell-kinetic analyses of the seminiferous epithelium. PMID- 8470826 TI - Differentiation of the mammalian retinal pigment epithelium in vitro: influence of presumptive retinal neuroepithelium and head mesenchyme. AB - The ancestor cells of the pigment epithelium of the mammalian eye are derived from the neuroepithelial cells of the neural plate. They are neurally determined in the process of neurulation but finally decide to follow the pigment cell lineage, whereas the adjacent tissue develops into the neuroretina and the optic stalk. This decision is most probably made in the developmental stage of eye cup formation. The pigment epithelium becomes restricted to the outer leaf of the eye cup and does not encroach on the adjacent neuroepithelial tissues of the internal leaf and the eye stalk. It is therefore supposed to be channelled by a locally confined determinant factor that has not yet been identified. In the present study, development of the mammalian eye and the neural versus pigment cell decision were investigated in mouse embryos. Three approaches were used to discover the source of the putative determinant involved in the process of neuroepithelial decision. First, eye primordia were cultured from stage 11 embryos (0 somites, early neural plate stage, embryonic day 7 1/2-8) to stage 16 embryos (34 somites, neural tube stage, ed 10); this is prior to pigment cell induction. The eye primordia were first cultured in head segments and their natural position. In these experiments, 50% of the ocular neuroepithelia developed along the nerve cell and glial cell lineage. However, the other 50% of the cultured specimens partly developed into pigment epithelia. In these specimens the determinant factors had obviously remained functionally intact in vitro. In the second type of experiment, the eye primordia were also cultured within the head segments, but with the prospective neuroretina selectively removed. This experiment should show whether the inner layer of the eye cup (the prospective neuroretina) is involved in the neuroepithelial lineage decision. In these experiments 90% of the cultured eye primordia failed to develop pigmented cells. The prospective neuroretina was therefore considered as a candidate for the production of an inductive factor. Finally, eye primordia from stage 14-15 embryos (13-29 somites, ed 9-9 1/2) were either transplanted into heterotopic tissues, such as mesenchymal organs, neuroepithelium or heterochronic muscle, or grown as controls in their natural position and tissue environment. In these conditions both transplanted eye primordia and controls bore pigmented epithelium. Hence, the lineage decision, whether to form neural or pigment cell, remained undisturbed in all epitopes tested. On the basis of these experiments, it seemed unlikely that the development of pigment cells was initiated by a mesenchyme-derived factor exclusively produced near the eye vesicle. PMID- 8470828 TI - Experimental study on the formation of the epicardium in chick embryos. AB - In chick embryos, the formation of the epicardium proceeds from the attachment of a secondary sinuventricular mesocardium. This mesocardium is formed by the adhesion of pericardial villi with the dorsal surface of the heart. It was the aim of this study to clarify the role of the pericardial villi in the formation of the epicardium. For this purpose, the contact between the pericardial villi and the heart was prevented by placement of a piece of the shell membrane between them. After re-incubation, the hearts of the experimental embryos could be assigned to one of two different groups: hearts completely lacking a secondary mesocardium (Group A), and hearts without the sinu-ventricular but with a dystopic secondary mesocardium (Group B). In Group A, the formation of the epicardium and subepicardial mesenchyme was found to be severely disturbed. In Group B, the formation of the epicardium proceeded from the point of attachment of a dystopic secondary mesocardium; defective development of the subepicardial mesenchyme was not encountered. These results support the view that the epicardium is derived from the pericardial epithelium. PMID- 8470827 TI - Fibroblast growth factor induces primitive streak formation in rabbit pre implantation embryos in vitro. AB - Culturing of rabbit pre-implantation embryos was performed in Ham's F10 medium supplemented with polyvinylpyrrolidone. Under these culture conditions, day 6 post coitum blastocysts increased their diameter within 24 h to 80% of that of day 7 blastocysts grown in vivo. Despite this substained growth, the embryonic disc remained undifferentiated with clear signs of degeneration after 24 h of culture. Basic fibroblast growth factor (bFGF) was able to overcome this developmental block. After 12 h of culture, day 6 blastocysts showed pear-shaped embryonic discs, and after 24 h, the primitive streak with Hensen's node was visible. The bFGF had no comparable effects on day 5 and day 7 blastocysts. The embryonic discs of day 5 blastocysts degenerated, even in the presence of bFGF, whereas day 7 blastocysts were able to form their primitive streak, also in the absence of bFGF. TGF beta 1 did not promote embryonic development in vitro. The data indicate that the onset of mesoderm formation in the rabbit is controlled by a growth factor of the FGF-family. PMID- 8470829 TI - Morphological evidence for secondary formation of the tail gut in the rat embryo. AB - The secondary body formation is a developmental mechanism occurring in the caudal part of the embryo in which embryonic structures arise from a mass of mesenchymal cells without previous formation of germ layers. The formation of the tail gut by this mechanism was investigated on transverse serial semithin and ultrathin sections of 12-, 13-, 14- and 15-day rat embryo tails. The tail gut, together with the tail portion of the notochord, originates from an axial mass of condensed mesenchymal cells named tail cord. Formation of the tail gut involves the appearance of large intercellular junctions among tail cord cells, and rearrangement of these cells around a newly formed lumen. Mesenchymal characteristics of these cells are gradually lost, and they simultaneously acquire the morphology of epithelial cells. Some cells of the tail cord, located ventral to the tail gut, do not participate in the tail gut formation and form a separate mass of cells without any definitive morphogenetic fate. This surplus group of cells is first evident in 12-day embryos, and it increases in mass during the following 3 days. In 15-day embryos, after the tail gut has completely disappeared, the surplus cells represent all that remains of the tail cord. The mesenchymal-epithelial transformation of the tail cord cells into the cells of the tail gut, and the appearance of the surplus cells, could be considered as the main morphological arguments for the secondary formation of the tail gut. PMID- 8470831 TI - Detection of HIV-1 by polymerase chain reaction and culture in seronegative intravenous drug users in an inner-city emergency department. AB - STUDY BACKGROUND: After a health care worker's unprotected exposure to a patient's blood, the current recommendation is to obtain consent from the source for serologic testing for HIV. If the test is negative, no further follow-up of the exposed provider is usually indicated. OBJECTIVE: To determine if patients testing negative for HIV-1 antibody on routine serology harbor occult HIV-1 infection. DESIGN: Cross-sectional, identity-unlinked, patient-related data and blood sample procurement for HIV-1 infection. SETTING: Inner-city university hospital emergency department with high HIV-1 seroprevalence among patients. TYPE OF PARTICIPANTS: IV drug users not known to have HIV-1 infection. MEASUREMENTS: Serum samples were analyzed for HIV-1 antibodies by enzyme immunoassay and Western blot. Peripheral mononuclear cells were analyzed for HIV-1 provirus by polymerase chain reaction and viral culture. MAIN RESULTS: Of 131 patients, 36 (27.5%) were Western blot-confirmed seropositive for HIV-1. Of the 95 seronegative patients, six (6.3%) were polymerase chain reaction positive, and one of these was confirmed with culture. The negative predictive value of standard serology was 93.5% with polymerase chain reaction alone and 98.9% with concordant polymerase chain reaction and culture results. CONCLUSION: There may be a significant number of ED patients in HIV-1 prevalent populations who have occult HIV-1 infection not detectable by serology at the time of a health care provider exposure. Although these data suggest that further prospective study is warranted to better quantify the frequency of this phenomenon, these preliminary data suggest that current Centers for Disease Control recommendations regarding provider exposures may need to be reappraised for certain situations. PMID- 8470830 TI - Alterations of heart development in Xenopus laevis by galactoside-binding lectin or its sugar hapten inhibitor. AB - The early heart anlagen of Xenopus laevis embryos were exposed to purified embryonic galactoside-binding lectin or its potent hapten inhibitor thiodigalactoside (TDG). Heart development was then studied using a variety of microscopical techniques. Conotruncal morphology and positioning with respect to the ventricle are altered in treated animals. In 34% of animals treated with lectin and 35% treated with TDG, the conotruncus leaves the ventricle from an abnormal location. Lectin or TDG treatments are also correlated with altered conotruncal shape, with the conotruncal regions showing greater radii of curvature compared to controls. Conotruncal myocyte differentiation is altered by the test treatments, with lack of development of organized myofibrillar arrays. Conotruncal cushion development is also affected. Changes occur in the shape and size of the primary conotruncal cushion, and alterations of outflow tract septation develop. Less maturation of ventricular myocytes is also observed in test animals. The results suggest that galactose-lectin interactions are important in heart development. PMID- 8470832 TI - Clinical use of the erythrocyte sedimentation rate in the evaluation of febrile intravenous drug users. AB - STUDY OBJECTIVE: To investigate the use of the erythrocyte sedimentation rate in the evaluation of febrile IV drug users. DESIGN: Prospective observational cohort study. SETTING: Municipal hospital emergency department. TYPE OF PARTICIPANTS: One hundred six IV drug users aged 18 years or older, with rectal temperatures of 37.8 C or more. INTERVENTIONS: Clinical and laboratory variables were obtained by trained research assistants, using a standardized data collection instrument. RESULTS: The erythrocyte sedimentation rate was the only variable consistently associated with illness severity in both the univariate and multivariable analyses (P < .0001). At an erythrocyte sedimentation rate of 100 mm/hr or more, the test had a specificity of 96% (95% confidence interval, 81% to 100%). In contrast, the erythrocyte sedimentation rate displayed a relatively poor sensitivity at low values (88% [95% confidence interval, 77% to 95%] at an erythrocyte sedimentation rate less than 20). CONCLUSION: An erythrocyte sedimentation rate of 100 or more should be regarded as a marker for serious illness in IV drug users with fever, but a "normal" erythrocyte sedimentation rate of less than 20 does not reliably exclude the presence of serious disease in this patient population. PMID- 8470833 TI - Emergency department screening for syphilis in pregnant women without prenatal care. AB - STUDY OBJECTIVE: To determine if there is a high seroprevalence of syphilis in pregnant women without prenatal care presenting to an urban emergency department. DESIGN: Prospective, nonblinded sampling of pregnant women without prenatal care with a comparison group of pregnant women with prenatal care from the obstetrics clinic. Patients in the ED setting were asked about such associated risk factors as previous syphilis and drug use. SETTING: Urban ED. TYPE OF PARTICIPANTS: Pregnant women without prenatal care. INTERVENTION: Patients were screened for syphilis using the automated reagin test. Reactive automated reagin tests were confirmed by the fluorescent treponemal antibody absorption. In addition, 44 patients with nonreactive automated reagin tests had confirmatory tests done. New cases were verified by the state health department. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients were included in the study. The average age was 25 years. Eight patients (11.1%) were diagnosed with previously undetected syphilis. Four patients (5.6%) had previously treated syphilis. The laboratory cost of screening was $248 per new case of syphilis detected. The study group was compared with 118 patients matched for age and race who presented to the obstetrics clinic for routine prenatal care. Two new cases of syphilis were discovered in the clinic population (1.7%). CONCLUSION: A high rate of syphilis infection was detected in this inner-city ED population presenting without prenatal care. This was higher than that found in the patients presenting for obstetrics care in the clinic. Patients can be screened effectively in the ED. PMID- 8470834 TI - Assessing the diagnostic value of an ECG containing leads V4R, V8, and V9: the 15 lead ECG. AB - STUDY OBJECTIVES: To assess sensitivity, specificity, and odds ratios of ECG findings on leads V4R, V8, and V9 for acute myocardial infarction. DESIGN: Prospective, two-stage cohort study. SETTING: A 660-bed university-affiliated community hospital. TYPE OF PARTICIPANTS: One hundred forty-nine admitted patients with suspected myocardial infarction or unstable angina. INTERVENTIONS: Standard 12-lead ECG followed immediately by V4R, V8, and V9. MEASUREMENTS: Initial ECG findings of ST-segment displacement, Q waves, T-wave inversion, and eligibility for thrombolytic therapy. RESULTS: Major abnormalities (ST-segment deviation, T-wave inversion, Q waves) were found on the extra three leads in 28.9% (43 of 149) of patients. Sensitivity of ST-segment elevation for acute myocardial infarction on 12 versus 15 leads increased from 47.1% to 58.8%, respectively, with no decrease in specificity. McNemar's pair-matched analysis for ST-segment elevation on myocardial infarction subgroup showed an association of ST elevation with the 15-lead ECG (P < .05). An eightfold increase in the odds of detecting ST elevation was found (90% confidence interval, 1.42 to 14.58); 22% of patients negative for ST elevation on 12 leads were positive on 15 leads. Analysis of ECG criteria for thrombolytic therapy presenting uniquely on extra leads showed an increased sensitivity from 35.3% to 44.1% on 12 versus 15 leads, respectively; there was a sixfold increase in the odds of meeting ECG thrombolytic therapy criteria (90% confidence interval, 0.34 to 11.66); 13.5% of patients not meeting criteria on 12 leads did so on 15 leads. CONCLUSION: The 15 lead ECG provides increased sensitivity and odds of detecting ST-segment elevation in acute myocardial infarction patients with no loss of specificity; its use may expand the selection of thrombolytic therapy candidates and provide a fuller ECG description of the extent of myocardial injury and necrosis. PMID- 8470835 TI - Emergency cardiac stress testing in the evaluation of emergency department patients with atypical chest pain. AB - STUDY OBJECTIVES: To determine the feasibility, safety, and reliability of emergency cardiac treadmill exercise stress testing (CTEST) in the evaluation of emergency department patients with atypical chest pain. DESIGN: Thirty-two patients with atypical chest pain, normal ECGs, and risk factor stratification having low-probability of coronary artery disease were evaluated prospectively using outpatient, emergency CTEST. Study patients were compared with a retrospectively selected sample of admitted patients diagnosed with atypical chest pain who met the study criteria and were evaluated with CTEST as inpatients. All patients had follow-up at three and six months after evaluation. SETTING: University-affiliated community teaching hospital with 65,000 annual ED visits. RESULTS: All patients had normal CTEST. No patient had evidence of coronary artery disease, myocardial infarction, or sudden death during the follow up period. The average length of stay was 5.5 hours for emergency CTEST patients versus two days for inpatients. The average patient charge was $467 for ED evaluation with emergency CTEST versus $2,340 for inpatient evaluation. CONCLUSION: Emergency CTEST is a safe, efficient, cost-effective, and practical method of evaluating selected ED patients with chest pain. It is a useful aid for clinical decision making and may help to prevent unnecessary hospital admissions. PMID- 8470836 TI - Loss and grief reactions after spontaneous miscarriage in the emergency department. AB - STUDY OBJECTIVE: To describe the psychological and functional consequences of miscarriage in women after emergency department treatment and to identify variables that are associated with feelings of loss and grief. DESIGN: A prospective telephone follow-up study. SETTING: The ED of an urban teaching hospital. TYPE OF PARTICIPANTS: A consecutive sample of 44 women who were treated for miscarriage. MAIN RESULTS: Women were contacted a median of 17.5 days after their miscarriage. Although the pregnancy had been planned by only 12 women (28%), 30 (70%) stated they wanted the pregnancy once they knew they were pregnant. Women commonly felt a sense of loss (82%) and most experienced some limitations with daily functioning (77%). Although wanting the pregnancy was associated with a sense of loss, 40% of the women who did not want the pregnancy experienced loss. CONCLUSION: Grief reactions are pervasive after spontaneous miscarriage. There is no subgroup of women who could be expected not to experience loss and grief. The ED management of the woman who miscarries should address the anticipated loss and grief. PMID- 8470837 TI - The use of structured, complaint-specific patient encounter forms in the emergency department. AB - STUDY OBJECTIVE: To assess the effect of preprinted, structured, complaint specific patient encounter forms on documentation, use of testing, and treatment compared with free-text record keeping. DESIGN: Nonrandomized case-control trial. SETTING: University-affiliated, tertiary referral hospital emergency department. METHODS: The records of all patients with lacerations, pharyngitis, asthma, or isolated closed-head injury during an eight-month period were reviewed. INTERVENTION: Use of structured complaint-specific patient encounter forms versus traditional free-text record keeping. MAIN OUTCOME MEASURE: The null hypothesis was that there would be no differences in documentation, test use, or practice when the structured forms were used compared with free-text record keeping. RESULTS: Differences in documentation that favored the use of the structured forms for all four problems studied were seen consistently. Not only was documentation improved, but test use also was affected in a way that decreased use. In addition, in certain areas (eg, treatment of pharyngitis), clinical practice also was changed. CONCLUSION: Structured, problem-specific ED records improve documentation and affect both resource use and clinical practice. These forms may be useful for improving communication and reimbursement as well as for medicolegal documentation. They provide a method for standardized quality assurance review and clinical data abstraction. Finally, they provide a method for active dissemination of clinical standards. PMID- 8470838 TI - Sociodemographic determinants in the hospitalization decision: evaluation of an emergency department interhospital transfer policy. AB - STUDY OBJECTIVES: To evaluate an emergency department's "treat and transfer" policy during a two-month period of reduced inpatient capacity by determining the number and characteristics of transferred patients not admitted as planned to the receiving hospital. DESIGN: Matched case-control analysis. SETTING: Public hospital adult ED. TYPE OF PARTICIPANTS: Patients transferred to other hospitals for admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve percent of patients (16 of 135) were not admitted after transfer during the first month, and 8% during the two-month period. Only IV drug use was found to be significantly associated with an increased risk of discharge without admission (odds ratio = 9.5; 95% confidence interval, 1.9 to 47.8). CONCLUSION: Patients transferred from the public hospital ED resulted in admission to the receiving hospital in 92% of transfers. A history of IV drug use was the only characteristic found to be associated with discharge without admission to the accepting hospital. PMID- 8470839 TI - Compliance with emergency department referral: the effect of computerized discharge instructions. AB - STUDY OBJECTIVE: To examine the effect of computerized discharge instructions on emergency department patient referral recommendations. DESIGN: Prospective, descriptive analysis and clinical trial. SETTING: Emergency medicine residency affiliated urban hospital with 568 beds and 29,000 annual visits. TYPE OF PARTICIPANTS: One thousand ED patients discharged to an outpatient referral network during a six-week period. INTERVENTION: Mandatory referral was provided in written or computerized (Logicare Corp, Eau Claire, Wisconsin) format for each 500-patient group. Demographic data and compliance, measured as appointment completion within 30 days, were analyzed using chi 2 with Yates' correction, Fisher's exact, and odds ratio comparisons (P < .05, 95% confidence interval). MEASUREMENTS AND MAIN RESULTS: The institution of computerized discharge instructions resulted in increased overall patient compliance from 26.2% to 36.2% (P < .0008) with odds ratio of 1.59 (1.2 to 2.1). Subset analysis showed increased compliance in patients who were more than 40 years old (32.5% to 61.1%), were female (28.7% to 39.7%) with a private physician (36.4% to 53.9%), established hospital relationship (26.1% to 38.9%), had nonurgent complaints (26.5% to 36.2%), were specifically diagnosed with strain or contusion (17.0% to 36.8%), or were referred to obstetrics/gynecology clinic (13.2% to 48.6%) (P < .001). CONCLUSION: Computerized discharge instructions were associated with improved compliance with ED referral recommendations, based on historic and contemporary controls. PMID- 8470840 TI - Use of a bilingual medical history questionnaire in the emergency department. AB - STUDY OBJECTIVE: To demonstrate that a complete and rapid clinical history can be obtained using a self-administered, bilingual questionnaire. DESIGN: A post-test experimental design was used to evaluate time spent obtaining the history and information completeness for the two groups. SETTING: Urban county emergency department. PARTICIPANTS: All patients were non-English-speaking Hispanic women who presented with gynecologic complaints. METHODS: Fifty-five patients completed a history questionnaire in Spanish on a form that displayed their responses in English on the carbon copy. In the control group, a history was obtained using a bilingual interpreter. RESULTS: Average completion time was significantly less (t = 14.38; P < .0001) for the experimental group (chi 2 = 5.67 minutes; SD, 1.89) than for controls (chi 2 = 14.58 minutes; SD, 4.19). There was no statistical difference in review criteria for documentation between groups. CONCLUSION: Using a bilingual questionnaire to obtain a clinical history results in more rapid patient evaluation without affecting the quality of information obtained. PMID- 8470841 TI - Proposals for health care reform: how do we evaluate them? AB - The Society for Academic Emergency Medicine suggests a systematic approach to evaluating proposals for reform of the medical care system. Described are the three components of the problem--access, cost, and quality. Then, goals are proposed for health care reform. With this background, we describe the major questions that reform proposals must address and the potential impact of reform on emergency medicine. Emergency physicians must actively support health reform legislation that is in the over-all best interest or our patients and our specialty, and work with the new federal administration to evaluate proposed changes. PMID- 8470842 TI - Social work technician program. AB - The increasing use of US emergency departments has resulted in increased patient delays and resultant dissatisfaction on the part of the patients and their families. Furthermore, recent studies have indicated that these delays may jeopardize the health of the ED patient. We describe a program designed to address these concerns. The Social Work Technician Program employs social work students nearing graduation as liaisons between medical personnel and ED patients and their families. This program has been found to promote patient satisfaction and welfare while providing the students with a valuable educational experience. PMID- 8470843 TI - The choice of thrombolytic agents in the emergency department. AB - STUDY OBJECTIVE: To assess the choice of thrombolytic agents in emergency departments and whether administrators and third-party payers are influencing choices because of cost differences. DESIGN: A telephone survey. TYPE OF PARTICIPANTS: ED medical directors, stratifying for hospital ownership, size, and regions of the United States. MEASUREMENTS AND MAIN RESULTS: One hundred twenty three ED medical directors completed the interview. Findings indicate that formularies include recombinant tissue-type plasminogen activator (rt-PA) in 94.3% of surveyed hospitals and streptokinase in 63.4%. Public hospitals were significantly less likely to have rt-PA on the formulary (P = .0001). Based on payer type, 68.9% to 77.5% of patients requiring thrombolysis receive rt-PA, with approximately 15% of EDs using it for 1% to 25% of patients and an additional 15% using it for 26% to 50% of patients. Fourteen medical directors (11%) reported that they delay treatment with rt-PA until authorization is provided by the health maintenance organization, and 40% indicated they would change their choice of agents if rt-PA was denied. Cardiologists were the primary decision makers regarding thrombolytic agents in all types of hospitals. CONCLUSION: Although rt PA is the most frequently selected thrombolytic agent, significant practice variations exist among hospitals. To avoid interference from third-party payers and administrators, physicians may need to make decisions regarding such expensive agents in more objective forums (eg, pharmacy and therapeutics committees) and be better prepared to defend the resulting practice guidelines. PMID- 8470844 TI - Clinton's health reform and emergency department volumes: a return visit. PMID- 8470845 TI - Acute urinary retention: an unusual presentation of appendiceal abscess. AB - Emergency physicians frequently encounter patients with acute urinary retention. Although most common among the elderly, pediatric and young adult patients occasionally may present with this complaint. The differential diagnosis and emergency department work-up must be age specific. We discuss the case of a young man who presented with acute urinary retention, subsequently found to be caused by undiagnosed appendicitis with appendiceal abscess formation. Only nine such cases have been reported in the literature thus far, with only one occurring in the nonpediatric population. This case represents the second such case to be reported. The importance of a thorough history, physical examination, and diagnostic work-up of patients who present with acute urinary retention, particularly those in the younger age group, is emphasized. PMID- 8470846 TI - Delayed splenic rupture in a drug addict. AB - We present the case of a drug addict who was admitted with abdominal pain but gave no history of trauma. He subsequently left the hospital against medical advice, only to be readmitted a few days later with persistent abdominal pain. He was found to have splenic rupture. This case emphasizes the importance of ruling out intra-abdominal trauma in any drug addict presenting with acute abdomen. PMID- 8470847 TI - Underutilization of Rh prophylaxis in the emergency department. PMID- 8470848 TI - Unstable occult cervical-spine fracture. PMID- 8470849 TI - Clinical policy for the initial approach to patients presenting with a chief complaint of seizure, who are not in status epilepticus. American College of Emergency Physicians. PMID- 8470850 TI - Variations in mortality and length of stay in intensive care units. AB - OBJECTIVE: To evaluate the amount of variation in in-hospital mortality and length of intensive care unit (ICU) stay that can be accounted for by clinical data available at ICU admission. DESIGN: Inception cohort study. SETTING: Forty two ICUs in 40 hospitals, including 26 hospitals that were randomly selected and 14 large tertiary care hospitals that volunteered for the study. PARTICIPANTS: A consecutive sample of 16,622 patients and 17,440 ICU admissions. MEASUREMENTS AND MAIN OUTCOMES: Data on selected demographic characteristics, comorbidity, and specific physiologic variables were recorded during the first ICU day for an average of 415 admissions at each ICU; hospital discharge status (dead or alive) and length of ICU stay were recorded for individual patients; and the ratio of actual to predicted in-hospital mortality, standardized mortality ratios, and the ratio of actual to predicted length of ICU stay were recorded for individual ICUs. RESULTS: Unadjusted in-hospital mortality rates for the 42 units varied from 6.4% to 40%, and 90% (R2 = 0.90) of this variation was attributable to patient characteristics at admission. The standard mortality ratio varied from 0.67 to 1.25. The mean unadjusted length of ICU stay varied from 3.3 to 7.3 days, and 78% of the variation (R2 = 0.78) was attributed to patient and selected institutional characteristics. The best performing unit had a length of stay ratio of 0.88, whereas the poorest performing unit had a ratio of 1.21. CONCLUSIONS: Clinicians can use readily available admission data to adjust for considerable variations in patient severity and type in different ICUs. Such data should permit precise evaluation and comparison of ICU effectiveness and efficiency, which varied substantially in this study, and result in improved methods of risk prediction and evaluation of new medical practices. PMID- 8470851 TI - Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A 4 year prospective study. AB - OBJECTIVE: To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid. DESIGN: A 4-year prospective study. SETTING: Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands. PATIENTS: The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study. INTERVENTION: During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 micrograms, or ipratropium bromide, 40 micrograms). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 micrograms two times daily. RESULTS: Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyperresponsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups. CONCLUSIONS: Adding beclomethasone, 800 micrograms daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients. PMID- 8470852 TI - Cancer risk in relatives of patients with common colorectal cancer. AB - OBJECTIVE: To quantify any risk for colorectal cancer in first-degree relatives of patients with common colorectal cancer and to define possible markers for increased risk. DESIGN: Case-control family study. PATIENTS: Relatives of colorectal cancer patients and of matched control patients from a one-surgeon practice. METHODS: Family medical histories were obtained for 7493 first-degree relatives and 1015 spouses of 523 case-control pairs. Reported diagnoses of colorectal cancer in relatives were verified in 79% of instances. RESULTS: By case-control analysis, the odds ratio was 1.8 (95% CI, 1.2 to 2.7) for one and 5.7 (CI, 1.7 to 19.3) for two affected relatives. By matched analysis of risk in relatives, the increased risk to parents and siblings was 2.1 times greater for case patients than for control patients (CI, 1.4 to 3.1); 3.7 times greater (CI, 1.5 to 9.1) with case patients diagnosed before 45; and 1.8 times greater (CI, 1.2 to 2.9) with case patients diagnosed at 45 years or older; and was independent of gender, type of relative, site of cancer, and type of cancer (single or multiple). The cumulative incidence among first-degree relatives was greater for case patients than for control patients (P < 0.001), and in case patients, greater for those diagnosed before 55 years of age (P < 0.001). The cumulative incidence (+/- S.E.) to age 80 was 11.1% +/- 1.3%, 7.3% +/- 0.8%, and 4.4% +/- 1.0% among relatives of case patients diagnosed before age 45 years, between 45 and 54 years, and at 55 years or older, respectively, and was 2.4% +/- 0.6% in relatives of control patients. CONCLUSIONS: First-degree relatives of patients with common colorectal cancer have an increased risk for colorectal cancer. This risk is greater if diagnosis was at an early and is greater when other first-degree relatives are affected. This increased risk should be considered when formulating screening strategies. PMID- 8470853 TI - Chronic active hepatitis associated with trazodone therapy. PMID- 8470854 TI - Risk factors for prostate cancer. AB - PURPOSE: To review the current state of knowledge regarding risk factors for prostate cancer. DATA SOURCES: Analysis of the literature through the use of MEDLINE as well as identification of papers through review of article bibliographies and the authors' personal files. Current data were also extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. DATA SELECTION: A review of risk factors for the development of prostate cancer. Emphasis was placed on identifying larger, controlled studies. DATA SYNTHESIS: The clinical incidence of prostate cancer is increasing. Risk factors for prostate cancer appear to include age, race, positive family history, vasectomy, and dietary fat intake. CONCLUSIONS: It appears that prostate cancer results from an interplay between endogenous hormones and environmental influences that include, most prominently, dietary fat. PMID- 8470855 TI - AIDS and the common man. PMID- 8470856 TI - Systems for comparing actual and predicted mortality rates: characteristics to promote cooperation in improving hospital care. PMID- 8470857 TI - The hazards of misguided compassion. PMID- 8470858 TI - Cost-effective treatment of Candida esophagitis. PMID- 8470859 TI - Cost-effective treatment of Candida esophagitis. PMID- 8470860 TI - Cost-effective treatment of Candida esophagitis. PMID- 8470861 TI - Selective decontamination of the digestive tract. PMID- 8470862 TI - Relation of adrenal androgen to insulin levels. PMID- 8470863 TI - Danazol for Henoch-Schonlein purpura. PMID- 8470864 TI - Intravenous gammaglobulin in a hypothyroid patient with the antiphospholipid antibody syndrome. PMID- 8470865 TI - Honing clinical skills. PMID- 8470866 TI - Honing clinical skills. PMID- 8470867 TI - Prolonged intubation injuries of the larynx: endoscopic diagnosis, classification, and treatment. AB - Laryngeal trauma from prolonged endotracheal intubation occurs in patients of all ages. Most changes are superficial and heal quickly. Injuries that are found consistently during intubation include nonspecific changes, edema, granulation tissue, ulceration, and other miscellaneous injuries. In this paper significant, severe, and lasting trauma of the larynx has been classified on the basis of the known factors in pathogenesis, observations made at endoscopy, and photographic documentation. This classification has required introduction of new descriptive terminology: "tongues of granulation tissue," "ulcerated troughs," "healed furrows," and "healed fibrous nodule." During intubation the degree of injury can be precisely assessed under general anesthesia by using telescopes for image magnification, thus assisting a decision whether to continue intubation or perform tracheotomy to minimize long-term morbidity. Changes that are found after extubation result from granulation tissue, ulceration, or a combination of both and have been illustrated on flow charts; a knowledge and understanding of these sequelae allows them to be identified by both indirect and direct laryngoscopy so that treatment can be planned. PMID- 8470868 TI - Hepatic acylcoenzyme A:cholesterol acyltransferase activity is low in hamsters fed apples in addition to a standard diet. AB - The effect of consumption of apples as a supplement to a standard diet on hepatic acylcoenzyme A: cholesterol acyltransferase (ACAT) activity was investigated in adult golden hamsters (Mesocricetus auratus). The experimental diet was given for 2 months. IN response to the high-fruit intake, the level of cholesteryl esters was reduced in the liver, and hepatic ACAT activity, determined in vitro under various conditions of incubation, was lowered by about 30%. Moreover, plasma cholesterol was redistributed among the lipoproteins, with a decrease in the cholesterol transported in the ApoB-rich lipoproteins. PMID- 8470869 TI - Effect of inpatient versus outpatient measurement protocol on resting metabolic rate and respiratory exchange ratio. AB - Resting metabolic rate (RMR) and respiratory exchange ratio (RER) were measured, using indirect calorimetry, in 9 healthy, male subjects (28.6 +/- 3.3 years) under three conditions: (1) an inpatient, meal-controlled protocol (IPM) in which subjects were fed an evening meal and slept overnight in the laboratory prior to the morning test; (2) an outpatient, meal-controlled protocol (OPM) in which subjects were fed the same meal but slept at home prior to being transported to the laboratory for testing, and (3) and outpatient protocol (OP) in which meal was not controlled, but subjects were instructed to fast for 12 h prior to testing. There were no statistically significant differences in RMR between protocols (IPM = 7,928 +/- 360, OPM = 8,015 +/- 331 and OP = 7,987 +/- 315 kJ/day) or in fasting RER (IPM = 0.82 +/- 0.01, OPM = 0.82 +/- 0.02 and OP = 0.81 +/- 0.02). These data indicate that in young, healthy males RMR and RER are similar when measured under inpatient or outpatient conditions. PMID- 8470870 TI - Biodistribution and metabolism of orally administered octacosanol in rats. AB - The biodistribution and metabolism of [8-14C]-octacosanol in rats were investigated to understand the mechanism of increased physical exercise and motor endurance by octacosanol. After 14C-octacosanol administered, radioactivity of octacosanol was mainly found in adipose tissue, especially in brown adipose tissue. Absorption of octacosanol is very low and mainly excreted through feces. The radioactivity of octacosanol was also partly expired as 14CO2. About 49% of the administered dose were excreted through different pathways. Metabolites of octacosanol are present in the urine. Octacosanol may be partly oxidized and degraded to fatty acids through beta-oxidation. PMID- 8470871 TI - IgG subclasses to food proteins in atopic and normal individuals. AB - IgG subclass antibodies to ovalbumin (OVA), gliadin (GLI) and beta-lactoglobulin (beta-lac) were determined in 18 atopic subjects and 18 age- and sex-matched controls. IgG antibodies to OVA and GLI were found predominantly as IgG4 subclass, with the IgG antibodies to beta-lac distributed evenly between IgG2, IgG3 and IgG4 in both groups. The proportion of anti-OVA IgG antibodies in the IgG3 subclass was significantly higher in the atopic group (22%) than in the nonatopic group (8%: p < 0.001). The proportion of anti-GLI IgG3 antibodies was also higher in the atopic group (43%) than the nonatopic group (24%: p < 0.001). OVA subclass antibodies in the atopic and nonatopic subjects were mainly IgG4, and GLI subclass antibodies were mainly IgG3 and IgG4. This study provides information on the distribution of IgG subclasses to food proteins, and in particular those related to protein GLI. The importance of IgG3 subclasses in atopic disease is highlighted; this phenomenon, to our knowledge, has not previously been reported. PMID- 8470872 TI - Multifrequency bioelectrical impedance as a measure of differences in body water distribution. AB - In 38 females, aged 21.3 +/- 1.8 years (mean +/- SD) and 22 males, aged 21.6 +/- 2.0 years, total body water (TBW) was assessed by bioelectrical impedance at a frequency of 100 kHz (Z100), and extracellular water (ECW) was assessed at a frequency of 1 (Z1) or 5 kHz (Z5). Impedance ratios of low frequencies (Z1 or Z5) to high frequency (Z100) were calculated as indicators of body water distribution. Furthermore, changes in body water distribution during the menstrual cycle were assessed in 16 females, aged 22.1 +/- 1.7 years, divided into subjects using or not using oral contraceptives. In general, the ratio ECW to TBW was lower in males compared to females, which was reflected in the ratios Z1/Z100 and Z5/Z100. However, the ratio Z5/Z100 reflected this difference less clear, probably because at 5 kHz the current partly passes the cell membranes. Weight changes during the menstrual cycle are generally accepted to be due to a retention of ECW. The ratio Z5/Z100 and the ratios Z1/Z100 and Z5/Z100 for those subjects not using oral contraceptives differed significantly between day with minimal and day with maximal weight. A negative correlation was found between weight change, still considering day with minimal and day with maximal weight, and change in impedance at 5 and 50 kHz for subjects not using oral contraceptives. It is concluded that differences in body water distribution are reflected by low-to-high impedance ratios. PMID- 8470873 TI - Influence of a single parenteral application of a 10% fish oil emulsion on plasma fatty acid pattern and the function of thrombocytes in young adult men. AB - 50 ml of a 10% fish oil emulsion (41% omega-3 fatty acids of total fatty acids) were infused for 1 h into the arm vein of young, healthy, male volunteers. The fatty acid composition of the plasma, aggregation of the blood platelets as well as the thromboxane synthesis, were measured before the beginning of infusion, 20, 60, 120, 360 and 1,440 min after the start of the fat infusion. In the first 60 min, the fatty acid composition of the plasma changed in correspondence with the supplied fatty acid pattern. At the end of the investigation it was again within the normal range. As a result of fat application thromboxane synthesis was reduced and the aggregation of the platelets was inhibited but it was normalized by the 1,440-min value. Fish oil emulsions might be beneficial for parenterally fed patients with a high risk of thrombosis. Therefore the performance of further investigations using a varying dosage and multiple application can be recommended. PMID- 8470874 TI - [Pelvic lymphatic excision using laparoscopy. Its value in the staging of tumors of the bladder]. AB - Laparoscopic surgical procedures are being evaluated in urologic diseases including bladder cancer. Patients with apparently localized tumors may have lymph node involvement indicating disseminated disease for which locoregional treatments are inadequate. Laparoscopic lymphadenectomy may be useful for staging, since neither noninvasive procedures nor intraoperative examination of lymph nodes removed during cystectomy are completely reliable. The technique is described in detail. Benefits in bladder cancer patients remain to be determined. PMID- 8470875 TI - [Natural history and prognostic factors of superficial tumors of the bladder]. AB - Forty-five patients with superficial bladder cancer managed by transurethral resection alone were studied longitudinally to identify factors associated with progression. Tumor grade, multiple tumor foci, and time to first recurrence were closely correlated with progression. Findings from this study are compared with previous reports. These data are useful to identify patients requiring more aggressive therapy, including intravesical anticancer drugs and BCG, and monitoring with closer-spaced cystoscopies. PMID- 8470876 TI - [Preventive treatment of superficial tumors of the bladder using intravesical BCG. Review]. AB - Local immunotherapy with BCG was first described by Zbar in an experimental model. The clinical use of BCG in human bladder carcinoma was proposed by Morales in 1976. Since then randomised studies have confirmed the value of BCG against recurrence and progression in superficial transitional cell carcinoma of the bladder (Lamm, Herr). However the optimal protocol has not been defined and the mode of action of BCG remains obscure. In this paper, the authors review the clinical results of BCG and its complications then focus on recent immunological data concerning its mode of action. Finally a practical protocol is proposed. PMID- 8470877 TI - [Radical cystectomy for cancer. Technic]. AB - Radical cystectomy is the treatment of choice for invasive bladder cancer. Morbidity and mortality associated with this procedure have been reduced substantially as a result of advances in surgical techniques and instruments. The cystectomy technique described herein offers satisfactory exposure and hemostasis, thus providing optimal conditions for achieving high-quality urinary diversion. PMID- 8470878 TI - [A procedure for bladder replacement using a low-pressure ileal reservoir]. AB - Goals pursued when constructing an ileal pouch after cystectomy include good capacity and distensibility, voluntary control of micturition with no residual urine, a sensation of fullness, and urinary continence. In addition, metabolic disorders due to reabsorption of urine components by the ileal mucosa require control. A bladder replacement technique using a low-pressure ileal reservoir is described and results in eighty patients are reported. Physiologic features of ileal urinary pouches are reviewed. PMID- 8470879 TI - [Results of the treatment of bladder tumors infiltrating the muscle]. AB - Recent studies have shown improvements in survival in patients with invasive bladder cancer, perhaps as a result of stage selection and reduced perioperative morbidity rather than of increased effectiveness of treatments. The main ongoing therapeutic trials (combined use of chemotherapy with either surgery or radiation therapy) aim at controlling occult metastases which may be present in up to 50% of apparently localized bladder cancers. Identification of risk factors for metastatic disease is therefore crucial. In this study, factors potentially associated with response to treatment were analyzed on the basis of a review of outcomes reported with current treatments. PMID- 8470880 TI - [The use of monoclonal antibodies in the evaluation of the aggressiveness of tumors of the bladder]. AB - Monoclonal antibodies produced using hybridoma technology have enabled identification of new tumor markers. Targets include tumor-associated antigens, growth factors and their receptors, blood group antigens, cell proliferation antigens, oncogene or tumor suppressor gene products, and markers for drug resistance. Immunohistochemical or flow cytometry studies performed with monoclonal antibodies can be used to determine the immunophenotype of normal and tumoral urothelium; specificity may be primarily for superficial or deep tumors, or for different tumor grades. A number of monoclonal antibodies have been found of prognostic value independently from conventional prognostic criteria. Others have shown diagnostic value. The most promising monoclonal antibodies are reviewed herein. PMID- 8470881 TI - [Surgical anatomy of the lymphatic drainage of the bladder]. AB - Descriptive anatomy teaches us that the lymphatic drainage of the bladder converges directly on to the middle and internal chains of the external iliac nodes, but never on to the external chain, sometimes on a sacral common iliac node and widely on internal iliac nodes. Surgical observations confirm this: no lymph node metastasis in the external chain of external iliac nodes is noticed, nor common iliac adenopathy without upstream invasion. On the basis of these descriptions, lymphadenectomy was performed from inguinal ligament to iliac bifurcation. Anatomical data largely explain pelvic recurrences due to the existence of unremoved common iliac nodes or unrecognized hypogastric nodes because of difficult access without sacrificing efferent branches of internal iliac artery. PMID- 8470882 TI - Effect of an extract from Phyllanthus amarus on hepatitis B surface antigen gene expression in human hepatoma cells. AB - It has been suggested that Phyllanthus amarus may be helpful in the treatment of hepatitis B virus infection. We studied the effect of an aqueous extract of P. amarus on the cultured hepatoma cell line HepA2. This cell line had been transfected with tandemly arranged HBV DNA and continued to synthesize and secrete both HBsAg and HBeAg. Extract of P. amarus reversibly inhibited cellular proliferation and suppressed HBsAg production but not HBeAg production in HepA2 cells. We also found that P. amarus suppressed HBsAg gene expression at mRNA level in a time-dependent manner, and selectively abolished the HBsAg gene promoter driven CAT activity. Our results demonstrate that P. amarus contains some active components which can suppress the HBsAg gene expression in human hepatoma cells. Such suppression may contribute the antiviral activity of P. amarus in vivo. PMID- 8470883 TI - Inhibition of Sindbis virus replication by cyclopentenone prostaglandins: a cell mediated event associated with heat-shock protein synthesis. AB - Cyclopentenone prostaglandins (PGs) have been shown to inhibit the replication of several DNA and RNA viruses. Here we report on the effect of prostaglandin A1 (PGA1) on the multiplication of a positive strand RNA virus, Sindbis virus, in Vero cells under one-step multiplication conditions. PGA1 was found to inhibit Sindbis virus production dose-dependently, and virus yield was reduced by more than 90% at the concentration of 8 micrograms/ml, which was non-toxic to the cells and did not inhibit DNA, RNA or protein synthesis in Vero cells. The cyclopentenone prostaglandin delta 12-PGJ2 was also shown to be a potent inhibitor of Sindbis virus replication. Virus-induced reduction of [3H]uridine uptake by cells was partially prevented by PGA1 treatment, which also caused a 1 h delay in the peak of virus RNA synthesis. SDS-PAGE analysis of [35S]methionine labeled proteins showed that PGA1 moderately inhibited the synthesis of the viral structural proteins E1, E2 and C, and induced the synthesis of a 72 kDa M(r) protein, identified as a heat-shock protein related to the HSP70 group, in both virus-infected and uninfected cells. Actinomycin D treatment completely prevented PGA1-antiviral activity, indicating that a cellular product is responsible for this action. PGA1-induced HSP70 is a good candidate for this role. PMID- 8470884 TI - Inhibition of duck hepatitis B virus replication by hypericin. AB - Hypericin was found to be active against a member of the hepatitis B virus family, duck hepatitis B virus (DHBV). After a single 1 h incubation with hypericin, cells stably-transfected with a clone of DHBV stopped producing infectious virus for several days, though virus-like particles continued to be released into the culture medium. Characterization of these virions revealed a buoyant density characteristic of infectious virus preparations and lower than that of virus cores, suggesting that the particles were enveloped. Western blot analysis suggested, however, that the viral preS protein in surface antigen particles and, by inference, in virions, was present in covalently cross-linked aggregates. Evidence of a similar level of aggregation of the core subunit of virion nucleocapsids was not found, nor was there evidence of a similar high level of aggregation of cell-associated core and preS proteins. Hypericin was only slightly virucidal against DHBV and culture medium from treated cultures did not block initiation of infection when added to DHBV susceptible cultures prior to a challenge with infectious DHBV. Thus, the primary antiviral activity of hypericin against DHBV replication appears to be exerted at a late step in viral morphogenesis. PMID- 8470885 TI - Siderophores. AB - Siderophores, defined as low-iron-induced virtually ferric-specific ligands, are widely distributed in microbial species where they function in the sequestration and transport of iron. In Escherichia coli biosynthesis of siderophores is negatively regulated at the transcriptional level by ferrous ion in conjunction with a repressor protein, Fur (ferric uptake regulation). Siderophores are a component of the virulence armamentarium of clinical isolates of E. coli and of certain other microorganisms pathogenic to man, animals, and plants. The mechanism whereby cells accumulate sufficient iron for activation of essential enzymes while, at the same time, avoiding excess of a potentially toxic element remains one of the most challenging problems in biochemistry. PMID- 8470886 TI - Vitamin A inhibits doxorubicin-induced membrane lipid peroxidation in rat tissues in vivo. AB - The antioxidant activity of vitamin A against lipid peroxidation induced by doxorubicin in rat tissues in vivo was investigated. A single ip injection of doxorubicin (30 mg/kg body wt) markedly raised the level of peroxidated lipids measured as TBARS and conjugated dienes in heart and brain membrane preparations. Other tissues, such as retina and liver, did not show any increase of lipid peroxides over control values. Pretreatment of rats with two daily subcutaneous injections of retinol palmitate (0.25 g/kg body wt), for 2 days, before injecting doxorubicin, inhibited peroxidation of heart and brain membrane lipids. The antioxidant action of vitamin A does not appear to be mediated by enhancement of antioxidant enzyme activities committed to detoxify oxygen radicals. Superoxide dismutase and catalase, measured in heart and brain cytosol, were not affected by the vitamin A treatment. On the contrary, a slight increase of catalase activity was observed in heart and brain cytosol from rats that had been treated with doxorubicin. Excess vitamin A may be localized in membranes. Appreciable increase of retinyl esters and retinol was measured in membrane preparations from rats that had been treated with vitamin A, with respect to control animals. Brain and heart membrane preparations from rats receiving vitamin A, assayed in vitro in the presence of an Fe3+ ascorbate induction system, showed a delay at the beginning of the lipid peroxidation and generated lesser amounts of TBARS, with respect to membranes from control rats. Thus, the increase of vitamin A within cell membranes results in an increased resistance of membrane lipids to peroxidation, both endogenously produced and induced in vitro. These results may be consistent with the hypothesis that vitamin A may act as a physiological antioxidant in cell membranes where it is localized. PMID- 8470887 TI - Hydrophobic affinity chromatography of human thrombin. AB - Hydrophobic affinity chromatography on p-chlorobenzylamido-agarose (p-CBA agarose) was used to characterize various modified forms of human thrombin. Native alpha-thrombin bound tightly to the column and was eluted with either acetonitrile or 1,4-dioxane, while the catalytically inactive prethrombin 2 did not bind to the matrix. Site-specific chemical modification with pyridoxal 5' phosphate resulted in the loss of at least 80% of fibrinogen clotting activity but did not influence the binding of thrombin to p-CBA agarose. Modification of thrombin with pyridoxal 5'-phosphate is thought to occur at the fibrinogen binding site and the heparin-binding site. In contrast, binding of thrombin to p CBA agarose was eliminated by modification of the active site histidine using either H-D-phenylalanyl-L-prolyl-L-arginine chloromethylketone or dansyl-L glutamyl-glycyl-L-arginine chloromethylketone but not with tosyl-L-lysine chloromethylketone. The presence of either hirudin or heparin blocked the binding of thrombin to p-CBA-agarose but dansyl-arginine-N-(3-ethyl-1,5-pentanediyl)amide had no effect. These results indicate that p-CBA agarose binds to thrombin outside of the enzyme active site and its use should be valuable in characterizing site-specific modified thrombins obtained by either protein engineering or chemical modification. PMID- 8470888 TI - Complete assignment of 1H and 13C nuclear magnetic resonance chemical shifts of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of the pathogenic yeast Candida albicans NIH B-792 strain. AB - To confirm correctness of the previous assignment study of H-1 protons of beta 1,2-linked mannooligosaccharides provided by Shibata et al. (Biochemistry 31, 5680-5686, 1992), another type of nonempirical assignment of the H-1 signals of the same oligosaccharides was achieved by adopting a sequential NMR assignment method that combines two-dimensional 1H-13C correlated spectroscopy, two dimensional 1H-1H correlated spectroscopy, and two-dimensional heteronuclear multiple-bond connectivity. Based on the above results, all of the 1H and most of the 13C signals in each oligosaccharide could also be assigned. The results of the proton assignment study provided sufficient evidence to confirm the correctness of that obtained in the previous H-1 proton assignment study. Furthermore, the existence of a regularity rule between the order of mannose units and its 1H and 13C chemical shifts has been revealed. PMID- 8470889 TI - Analysis and modification of thiols in the hemolymph juvenile hormone binding protein of Manduca sexta. AB - Hemolymph-induced in vitro modifications of the hemolymph juvenile hormone binding protein from the tobacco hornworm, Manduca sexta, were analyzed by polyacrylamide gel electrophoresis, Western blots, and equilibrium dialysis. Upon hemolymph melanization, a complex reaction involving polymerization of phenolic compounds, multiple forms of the protein were detected. Under melanizing conditions, one slower- and several faster-migrating proteins were observed. When the hemolymph was treated with 100 mM catechol, a melanin precursor, two well defined forms of the binding protein appeared. When the protein was incubated with excess catechol (> 100 mM) a single faster-migrating form appeared. Both fast and slow forms bound juvenile hormone I with similar efficiency. These results were duplicated using the thiol modifying reagents p chloromercurobenzoate and N-ethylmaleimide, suggesting modification of cysteine residues. Using differential alkylation, it was determined that hemolymph juvenile hormone binding protein contained two cystine and two cysteine residues. One of the cysteines is exposed and readily accessible for modification. Since modification of the exposed free thiol did not alter binding, it presumably resides outside the hormone-binding domain. The analyses support the observation that there is a single form of the hemolymph juvenile hormone-binding protein in our strain of M. sexta. PMID- 8470890 TI - Identification of the hydrophobic ligand-binding region in recombinant glutathione S-transferase P and its binding effect on the conformational state of the enzyme. AB - Recombinant glutathione S-transferase P (GST-P) was purified in a homogeneous state. Fatty acid analysis of the enzyme revealed that the final enzyme preparation endogenously bound fatty acids, mostly palmitic acid or stearic acid, which were difficult to dissociate from the complex. Temperature-dependent analysis by 1H NMR indicated that the molecular motion of fatty acids was strongly restrained under physiological conditions, which was significantly different from that of serum albumin. On the other hand, there existed another hydrophobic ligand-binding region in GST-P, to which 1-amino-8 naphthalenesulfonic acid and bilirubin would bind with relatively lower affinity than the endogenously bound fatty acid. The hydrophobic ligand-binding region was determined to be around 141-156 residues from the N-terminus by procedures including association of the enzyme to fatty acid-linked Sepharose and affinity labeling with fluorescent fatty acid. Furthermore, circular dichroism analysis showed that the binding of hydrophobic ligand to GST-P produced a remarkable conformational change of the enzyme, which led to states devoid of transferase activity. In addition, the hydrophobic ligand binding caused a significant fluorescence quenching of tryptophan 38, which was assumed to be located at the active center of GST-P. It could be the result of a conformational change of the active center of the enzyme. PMID- 8470891 TI - Studies on fibronectin and its domains. II. Secondary structure and spatial configuration of fibronectin and of its domains. AB - Fibronectin (FN) from human plasma, as well as recombinant proteins derived from two of its major domains, the N-terminal fibrin-binding domain (FBD) and the cell binding domain (CBD), were studied by circular dichroism (CD), Fourier transform infrared (FTIR), and fluorescence spectroscopies. Secondary structure estimations derived from both FTIR spectra and far uv CD indicate significant differences between FBD and CBD proteins. Thus, the CBD 33-kDa protein contains 80% beta sheet and 20% beta-turns, whereas the three refolded FBD recombinant proteins studied, the 12-, 18.5-, and r31-kDa proteins, as well as the plasma-derived p31 kDa protein, all contain some percentage of aperiodic structure, ranging from 14 to 23% for both 31-kDa proteins, and between 33 and 46% for the smaller 12- and 18.5-kDa proteins. The amount of aperiodic structure increases drastically (from 23 to 67%) in a misfolded recombinant 31 kDa, the scrambled 31 kDa. Both native FN and a chimeric 45-kDa protein, consisting of both the FBD 12-kDa and the CBD 33-kDa proteins, were found to resemble the CBD 33-kDa protein itself, i.e., consisting only of beta-sheet and beta-turns and being free of aperiodic structure. These differences between two types of conformation are corroborated by the differences in the environment and spatial configuration of the aromatic amino acids of these proteins, as evidenced from near uv CD and intrinsic fluorescence spectroscopies. Thus, in the near uv CD the typical CBD proteins, i.e., the 33- and 45-kDa proteins display a maximum at 294 nm, whereas the FBD proteins, except for the scrambled 31-kDa protein, all have a characteristic strong negative peak at 300 nm. Similarly, the lambda max of the emission spectra of the whole FN and the 33- and 45-kDa proteins are characteristically blue shifted (317-326 nm) and with high normalized intensity, when compared with the relatively red-shifted lambda max (338-340 nm) and low intensities of the folded FBD proteins. The scrambled 31-kDa protein again takes exception, having a relatively high normalized intensity due to misfolding. The two major conclusions from this work, attained by a combination of four spectroscopic methods, are: (a) functionally different FN domains, i.e., the FBD and CBD adopt totally different conformations, with the CBD having an almost exclusive beta structure; (b) the functional specificity of the various domains of FN may depend on subtle differences in the flexibility in their protein backbones, with the FBD being more flexible than the CBD. PMID- 8470892 TI - Purification and characterization of an alpha-L-fucosidase from Pomacea canaliculata. AB - An alpha-L-fucosidase (EC 3.2.1.51) was isolated from the hepatopancreas of Pomacea canaliculata. The enzyme was purified 285-fold from the crude enzyme extract by procedures involving first heat treatment, ammonium sulfate fractionation, second heat treatment, and chromatography on DEAE-Sepharose, hydroxylapatite, and L-fucosylamine-CH-Sepharose. When assayed by using p nitrophenyl glycosides as substrates, the final preparation was free from other glycosidase activities and gave a single protein band which corresponded to alpha L-fucosidase activity on disc gel electrophoresis. The molecular weight of the enzyme was estimated to be 260,000 by Sephacryl S-300 column chromatography. The enzyme has two optimum pH values, 2.5 and 5.0, and the apparent Km value and the maximum velocity for p-nitrophenyl alpha-L-fucoside at both pH were calculated to be 0.45 mM and 1.46 mumol/min/mg of protein, respectively. The enzyme was shown to hydrolyze the Fuc alpha 1-->2Gal, the Fuc alpha 1-->4GlcNAc, and the Fuc alpha 1-->6GlcNAc linkages, but hardly acts on the Fuc alpha 1-->3GlcNAc linkage in various oligosaccharides. PMID- 8470893 TI - Structure of D-glyceraldehyde-3-phosphate dehydrogenase from Palinurus versicolor carrying the fluorescent NAD derivatives at 2.7 A resolution. AB - Ultraviolet irradiation of carboxymethylated D-glyceraldehyde-3-phosphate dehydrogenase leads to the formation of a fluorescent NAD derivative. The structure of the enzyme from Palinurus versicolor carrying this derivative has been determined by molecular replacement and refined using the restrained least squares method to 2.7 A with a final crystallographic R-factor of 0.205. The polypeptide chain folding and subunit arrangement closely resemble the known structure of Homarus americanus GAPDH. The structure at the modified active site confirms that the photochemical reaction is a half-of-the-sites reaction and occurs in the red and yellow subunit pair. The stereochemical relationship between the Trp residues at the active site shows that Trp 310 is most probably involved in a radiationless energy transfer to the fluorophore. A large solvent channel connecting the catalytic and NAD(+)-binding sites was found parallel to the crystallographic axis alpha from packing analysis, suggesting that this crystal form may be suitable for a kinetic crystallographic study of the apoenzyme. PMID- 8470894 TI - Combined effects of streptozotocin-induced diabetes plus 4-methylpyrazole treatment on rat liver cytochrome P4502E1. AB - The content and activity of cytochrome P4502E1 is increased in the diabetic state, primarily due to stabilization of the P4502E1 mRNA. Chemical inducers such as 4-methylpyrazole (4MP) increase P4502E1 content by stabilization of the protein. Experiments were carried out to evaluate the combined effects of 4MP and streptozotocin-induced diabetes on P4502E1 protein, catalytic activity and mRNA levels. Immunoblots showed an elevated content of P4502E1 after treatment with 4MP or streptozotocin, which was further increased when the two treatments were combined. Similarly, catalytic activity with effective substrates for P4502E1 was increased by the two separate treatments, and further increased by combined treatment. In all treatment groups, catalytic activity was strongly inhibited by antibody against P4502E1. The content of P4502E1 and catalytic activity in the 4MP plus streptozotocin group appeared to be additive of the values for the separate treatments. P4502E1 mRNA levels were elevated by the streptozotocin treatment but not by 4MP treatment; combined treatment with both inducers did not elevate P4502E1 mRNA levels beyond the increase produced in the diabetic state. CCl4 decreased cellular viability in hepatocytes from streptozotocin- or 4MP treated rats, and increased toxicity was found after treatment with both inducers. These results contrast the mechanisms of induction of P4502E1 by streptozotocin and 4MP, and suggest that each individual mechanism is maintained when the two inducers are administered such that effects on P4502E1 protein and catalytic activity, but not mRNA, are additive of values found for each inducer alone. The diabetic state may be associated with increased sensitivity to toxins which are activated by P4502E1, especially if chemical inducers similar to 4MP, e.g., ethanol, isoniazid are also present. PMID- 8470895 TI - Isolation and characterization of a differentiation-dependent gene in the human colonic cell line HT29-18. AB - The human colonic epithelial cell line HT29, and its clonal derivatives HT29-18 and HT-29-18-C1, differentiate in vitro. Differential screening of a subtraction cDNA library enriched for sequences unique to HT29-18-C1, a highly differentiated subclone of HT29-18, resulted in the isolation of a differentiation-dependent cDNA clone, A4. A full-length clone encoding A4 was obtained and sequenced to its entirety. It is 945 bp in length and contains an open reading frame (ORF) of 456 bp. The amino acid sequence deduced from the ORF reveals a polypeptide of 152 amino acids with a predicted molecular mass of 17,000 Da, a size confirmed by coupled in vitro transcription and translation directed by the full-length A4 cDNA. This polypeptide contains four potential membrane-spanning domains and consensus sequences for N-linked glycosylation as well as phosphorylation sites for protein kinase C and casein kinase II. Comparison of A4 to published DNA and protein sequences revealed no significant homology. Genomic Southern blot analysis suggests that the gene is present in a single copy within the human genome and is conserved in the rat. Northern blot analysis of RNA obtained from various rat tissues shows that the expression of the A4 gene is tissue-selective and is enriched in colonic mucosa. In situ hybridization using human intestinal tissues indicates that the expression of A4 follows a gradient along the crypt-to villus axis with the most abundant message occurring in the lower half of the crypt. Furthermore, nuclear run-on assays suggest that the induction of the A4 gene during differentiation of HT29-18 is regulated at a transcriptional level. A clone was isolated from a human genomic library and found to contain all five exons of A4. S1 nuclease analysis localized the start site of transcription to an adenosine residue 91 nucleotides upstream from the ATG translation initiation codon. Examination of the immediate sequence 5' to the mRNA start site reveals no TATA box and multiple known enhancer sequences. A4 is also noted to share certain features with the gene encoding the cystic fibrosis transmembrane conductance regulator protein. They include a similar vertical distribution of expression along the intestinal epithelium, enhanced transcription upon differentiation of HT29-18, and multiple shared putative regulatory sequences in the promoter regions. Further characterization of the mechanisms regulating expression of the A4 gene could contribute to the understanding of mammalian intestinal differentiation. PMID- 8470896 TI - Activity of human DNA polymerases alpha and beta with 2-chloro-2'-deoxyadenosine 5'-triphosphate as a substrate and quantitative effects of incorporation on chain extension. AB - When 2-chloro-2'-deoxyadenosine 5'-triphosphate (CldATP) is incorporated into DNA by human polymerases alpha and beta (Hpol alpha, Hpol beta) the rate of chain extension decreases. In the present study primer extension has been quantitated by estimating the concentration of each successive oligonucleotide product at a series of time points. This has permitted calculation of pseudo-first-order rate constants for successive nucleotide additions to primer. By this method it has been shown that rate constants for CldATP addition are 79-100% of those for dATP in the case of Hpol alpha, and 26-153% with Hpol beta. The concentrations of CldATP for half maximum velocity is 0.6 microM for Hpol alpha, and 6 microM for Hpol beta, each about twice the value for dATP. Thus, CldATP is a good substrate for both enzymes but is more efficiently used by Hpol alpha. Addition of a single analogue residue by Hpol beta to any of seven primers decreases the rate constant for addition of the next nucleotide to 2-7% of that after dAMP addition and further extension is negligible. Consecutive additions of analogue residues by Hpol alpha progressively decrease the rate of subsequent extension, and after five consecutive additions extension virtually terminates. These effects probably make a major contribution to the cytotoxicity of chlorodeoxyadenosine and its therapeutic usefulness as an antileukemic agent. PMID- 8470897 TI - Nicotinamide mononucleotide adenylyltransferase activity in human erythrocytes. AB - Nicotinamide mononucleotide adenylyltransferase (NMN-AT) activity has not hitherto been demonstrated in human red blood cells, owing to its low activity. Since it is usually located in the nucleus, the possibility of finding it in human erythrocytes was excluded. Here we report the first demonstration and characterization of NMN-AT in human red blood cells, by an HPLC method. The enzyme is Mg2+ dependent, with a Km of 0.303 mM for nicotinamide mononucleotide and 0.103 mM for ATP, and a Vmax of 346 nmol g Hb-1 h-1. The crude preparation is also active on nicotinic acid mononucleotide, producing nicotinic acid adenine dinucleotide. NMN-AT activity is inhibited by nicotinic acid mononucleotide, and nicotinic acid adenylyltransferase is inhibited by nicotinamide mononucleotide. Fiftyfold purification of NMN-AT was achieved by DEAE-Toyopearl chromatography, and the kinetic characteristics were determined. The partially purified preparation maintained its nicotinic acid adenylyltransferase activity. These findings are discussed in light of the regulation of NAD metabolism in human red blood cells. PMID- 8470898 TI - Regional differences in sulfated oligosaccharides of rat gastrointestinal mucin as detected by two-dimensional chromatography. AB - Radiolabeled sulfated mucin was obtained from rat gastrointestinal tract tissue (corpus, antrum, duodenum, jejunum, ileum, or colon) incubated with [35S]sulfate in vitro by fractionation of extracts on Superose 6 followed by purification with CsCl density gradient centrifugation. Significant amounts of 35S-labeled mucin were obtained from each tissue and radioactivity differed according to region, in the order colon > duodenum > jejunum > corpus > antrum > ileum. Gel-permeation chromatography of 35S-labeled oligosaccharides liberated from each mucin by alkaline-borohydrate treatment indicated the 35S-labeled oligosaccharides of each mucin differ with respect to elution position. Further examination of fractions eluted from the gel-permeation column by thin-layer chromatography showed region specific chromatograms for the sulfated oligosaccharides. Thus, not only the degree of sulfate incorporation but sulfated oligosaccharide structure differs according to the region in gastrointestinal mucin. PMID- 8470899 TI - Use of trinitrobenzensulfonate for affinity labeling of lysine residues at phosphate binding sites of some enzymes. AB - Trinitrobenzensulfonate, a reagent for lysine residues, inactivates lamb liver 6 phosphogluconate dehydrogenase through affinity labeling. Complete inactivation is due to the binding of only one residue of reagent per enzyme subunit. Other enzymes with a phosphate binding site are also inactivated by affinity labeling. It appears that trinitrobenzensulfonate, when used at low concentrations, first binds to a phosphate binding site, then reacts with a nearby lysine residue. This reagent presents some advantages over pyridoxal phosphate, which has similar characteristics. PMID- 8470900 TI - Homocysteine-dependent demethylation of trimethylselenonium ion and selenobetaine with methionine formation. AB - In the presence of rat liver cytosol and homocysteine, trimethylselenonium ion (TMSe+) underwent time-dependent demethylation to dimethylselenide with the concurrent formation of methionine. Convenient methods were developed for assay of this activity using either radioactive methods based on the gamma emitting isotope 75Se or nonradioactive HPLC assay of methionine. The rate of demethylation was linear with protein concentration and dependent on homocysteine, which could not be replaced by cysteine, glutathione, or dithiothreitol. The TMSe+ demethylation rate was inhibited by the addition of betaine, sulfobetaine (dimethylthetin), or dimethylglycine. The Km for TMSe+ was 8 mM compared to 0.04 mM for betaine, but the rate of TMSe+ demethylation was approximately 50-fold that of betaine when both were assayed at 25 mM. Methionine was also produced from selenobetaine, selenobetaine methylester, and sulfobetaine. The selenium analogues of betaine inhibited the demethylation of TMSe+ with only minor decreases in methionine production, indicating substrate competition. In preliminary studies aimed at the partial purification of the TMSe+:homocysteine methyltransferase activity, the enzyme was found to have chromatographic and heat stability characteristics similar to betaine:homocysteine methyltransferase. The data indicate that betaine:homocysteine methyltransferase, or a very similar enzyme, is involved in the demethylation of TMSe+ and show that TMSe+, an in vivo urinary selenium metabolite of many selenium compounds, is not biologically inert. PMID- 8470901 TI - Measurement of uric acid as a marker of oxygen tension in the lung. AB - Changes in O2 tension such as those associated with hypoxic ischemia or hyperoxia may potentially modulate purine nucleotide turnover and production of associated catabolites. We used an isolated perfused rat lung preparation to evaluate the effect of O2 tension on pulmonary uric acid production. Three O2 concentrations (21%, normoxia; 95%, hyperoxia; 0%, hypoxia) were utilized for both pulmonary ventilation and equilibration of recirculating perfusate. All gas mixtures contained 5% CO2 and were balanced with N2. We used Certified Virus Free Sprague Dawley male rats weighting 250-300 g, four to five rats in each exposure regimen. After a 10-min equilibration period, we measured uric acid levels at 0 and 60 min in lung perfusate and at 60 min in lung tissue. After 60 min of ventilation/perfusion, we observed significant uric acid accumulation in both lung tissue (25-60%) and perfusate (8- to 10-fold) for all three O2 regimens. However, hypoxia produced substantially greater net uric acid concentrations (net = the difference between zero and 60 min) than either normoxia or hyperoxia (1.5 fold in lung tissue, and 2-fold in perfusate, respectively). The data suggest that pulmonary hypoxia results in greater purine catabolism leading to increased uric acid production. Vascular space uric acid, as measured in the recirculating perfusate, was proportional to lung weight changes (r = 0.99) with hypoxia exhibiting the greatest values, possibly reflecting a linkage between tissue perturbation and uric acid release. Thus, measurement of uric acid may serve as a useful marker of adenine nucleotide turnover and lung injury. PMID- 8470902 TI - Solid-state NMR analysis of crosslinking in mussel protein glue. AB - Solid-state 13C and 15N NMR spectra have been obtained of intact adhesive plaques from the mussel Geukensia demissa labeled by L-[6-13C,6-15N]lysine. The plaques are rich in a polyphenolic protein glue which has 50 or more repeats of a nonapeptide sequence with one lysine per repeat. The average isotopic 15N enrichment of lysyl epsilon nitrogens in the plaques was 4%. These lysyl amines are not involved in ionic complexes and do not form observable concentrations of covalent crosslinks. PMID- 8470903 TI - Molecular dimensions and properties of N-[1-(2-hydroxyethyl)-2-nitro-1H-imidazol 1-yl]acetamide (SR2508). AB - Hypoxic cells in tumors are resistant to radiation and chemotherapy treatment. To decrease this resistance, 2-nitroimidazoles are used as radiation and chemical sensitizers in the treatment of tumors. Their use is marred by their toxicity. Therefore, the compound SR2508, a new 2-nitroimidazole derivative, was introduced in an attempt to obtain a less toxic nitroimidazole than those used thus far. The molecular structure and conformation of SR2508, determined from X-ray diffraction studies, is reported. The compound, formula C7H10N4O4, molecular weight 214.18, crystallizes in the monoclinic system, space group P2(1)/c, unit cell dimensions a = 12.052(3), b = 11.116(4), c = 7.330(2) A, beta = 106.94(2) degrees, V = 939.4(5) A3, Z = 4. The crystal structure was refined to Robs = 0.041. The imidazole and C-NO2 groups are each planar and inclined at 6.6 degrees to each other. The side chain, which contains an amide group, is also planar. There are hydrogen bonds between different molecules and they involve O(11) and O(15), as well as N(12) and O(15). When compared to other 2-nitroimidazoles that have been clinically tested, the hydrogen bonds in SR2508 account for the increased hydrophilic character of the compound. Based on the crystal structure data, models for a possible interaction between SR2508 and DNA have been proposed. PMID- 8470904 TI - Purification and characterization of monkey (Macaca nemestrina) tracheobronchial mucin. AB - A major mucin glycoprotein was purified from monkey (Macaca nemestrina) bronchoalveolar lavages by gel filtration, delipidation, and a series of density gradient centrifugations in cesium trifluoroacetate/guanidinium chloride. Lipids noncovalently associated with the mucin amounted to 24-36% by weight and consisted primarily of phospholipids and glycolipids. The mucin preparation was free of low-molecular-weight protein/glycoprotein contaminants, glycosaminoglycans/proteoglycans, and nucleic acids. The weight-average molecular weight and radius of gyration of the mucin in buffer containing 6 M guanidinium chloride was estimated to be approximately 1.56 x 10(6) and 100 nm, respectively, by laser light scattering technique. When the mucin was dissolved in 0.15 M NaCl, a considerably higher molecular weight of approximately 5.05 x 10(6) and a larger radius of gyration of approximately 127 nm were observed suggesting aggregation of the mucin molecules. Amino acid composition of the glycoprotein was characteristic of mucins with threonine, serine, glutamic acid, proline, glycine, and alanine comprising 63%. The total carbohydrate content was 71.5% and consisted of GalNAc, GlcNAc, Gal, sialic acids, and fucose in the molar ratio of 1.0:2.2:2.4:1.4:1.2 with no detectable mannose. Alkaline borohydride treatment indicated that 65% of the threonine and 27% of the serine are substituted by saccharides via GalNAc residues. An antisera produced against the purified mucin was found to react well with the native and weakly with the deglycosylated mucins and will be useful for immunoassays. A second, minor, mucin glycoprotein obtained during the purification was also partially characterized. PMID- 8470905 TI - Identification and regulation of rat squalene synthetase mRNA. PMID- 8470906 TI - Effects of radon inhalation on biological function--lipid peroxide level, superoxide dismutase activity, and membrane fluidity. AB - We administered radon (Rn) to rabbits by inhalation and examined changes in the lipid peroxide (TBARS) level, superoxide dismutase (SOD) activity, and membrane fluidity in various organs to clarify the therapeutic effects of Rn. The lipid peroxide level of the brain was significantly decreased immediately after Rn inhalation for 90 min in both the low concentration group (about 7-10 kBq/liter) and the high concentration group (about 14-18 kBq/liter) as compared with that in the control group. It further decreased in the low concentration group but slightly recovered in the high concentration group 2 h after inhalation. The lipid peroxide level of the lung showed no change immediately after inhalation but decreased significantly in both groups 2 h after inhalation. With regard to SOD activity in the brain and lung, only that in the brain showed significant increase in the high concentration group immediately after inhalation; no other change was observed. Membrane fluidity, especially the fluidity of membrane protein, was significantly increased in the brains of both groups immediately after inhalation, and that 2 h after inhalation in the lung was significantly increased in both groups. These findings suggest that the inhalation of Rn at Rn springs contributes to the prevention of brain disorders related to peroxidation reactions by promoting these physiologic changes. PMID- 8470907 TI - Phosphofructokinase from liver of the rainbow trout, Oncorhynchus mykiss. AB - Phosphofructokinase (PFK) from liver of the rainbow trout Oncorhynchus mykiss was purified to homogeneity with a recovery of 35% of total activity. The purified enzyme was a homotetramer with a native molecular weight of 297,000 +/- 16,000 and a subunit M(r) of 76,000 +/- 3000. Arrhenius plots of enzyme activity were linear over 5-27 degrees C with an activation energy of 52.3 +/- 2.1 kJ/mol. The binding of fructose 6-phosphate was cooperative. High ATP increased the Hill coefficient and produced a marked allotropic inhibition of the enzyme activity. The affinity of the enzyme for fructose 6-phosphate was increased by the addition of the enzyme activators such as inorganic phosphate, ammonium ions, AMP, and fructose 2,6-bisphosphate; the activators also reduced the inhibitory effect of ATP. Trout liver PFK was activated by phosphoenolpyruvate at physiological concentrations but was not affected by citrate. PMID- 8470908 TI - Inhibition of NAD(P)H:quinone acceptor oxidoreductase by flavones: a structure activity study. AB - A structure-activity study was carried out to determine the important regions of baicalein and oroxylin A, two flavones isolated from the Chinese herb Scutellariae radix, in inhibiting NAD(P)H:quinone acceptor oxidoreductase (EC 1.6.99.2; DT-diaphorase). This quinone reductase is a vitamin K reductase. It is a target for and has been used as a model enzyme to investigate the mode of action of oral anticoagulants. The two flavones were found to inhibit this quinone reductase in nanomolar ranges. The 5-hydroxyl, 7-hydroxyl, 8-hydroxyl, and 2-phenyl groups of these flavones were found to be important for their inhibition of the enzyme. The inhibition profiles of the flavones on the NADH menadione reductase activity, the NADH-potassium ferricyanide reductase activity, and the NADH-methyl red reductase activity of this enzyme were different. Therefore, even though the flavones were found to be competitive inhibitors with respect to NADH, they probably did not inhibit the enzyme by binding to the nicotinamide nucleotide binding site. Inhibition kinetic studies which indicated that these compounds bound to different sites than those for dicoumarol and phenindone were performed. These results indicate that these flavones are a new type of inhibitor of NAD(P)H:quinone acceptor oxidoreductase and potentially useful as anticoagulant drugs. PMID- 8470909 TI - The binding of Cd(II) to the hemocyanin of the Mediterranean crab Carcinus maenas. AB - The interaction of Carcinus hemocyanin with Cd(II) was studied. The incubation of the apoprotein with the metal yields a derivative containing 1 g-at. of EDTA stable Cd(II) per 75 kDa. Spectroscopic data ruled out Cd(II) coordination to tryptophan or cysteine residues. The optical activity and fluorescence properties of the protein are affected by Cd(II) binding and indicate a rearrangement of tryptophan residues. The poor Cd(II) binding to the oxy-form and the resistance of Cd(II)-hemocyanin to EDTA treatment and to the regeneration by Cu(I) strongly indicate that Cd(II) binding to apohemocyanin occurs at the copper-free active site. During the metal-binding process, a marked increase of light scattering is observed. This effect, however, is reversible provided that the incubation medium contains SCN- and glycine as exogenous ligands of the metal in the bulk solution. PMID- 8470910 TI - Stereoselective interaction of 2-halo-acyl-CoA derivatives with medium chain acyl CoA dehydrogenase from pig kidney. AB - Several 2-halo-acyl-CoA derivatives have been synthesized to examine the interaction of these potential inhibitors of mitochondrial beta-oxidation with the purified medium chain acyl-CoA dehydrogenase from pig kidney. Racemic 2-bromo , 2-chloro-, and 2-fluoro-octanoyl-CoA thioesters show 6.6, 33, and 3.5% of the activity of octanoyl-CoA in the standard assay system, respectively. Only the S enantiomer of these 2-substituted analogues is a significant substrate of the dehydrogenase, with S-2-bromo-octanoyl-CoA showing a rate of 18% that of octanoyl CoA, compared to about 1% for the R-isomer. The observations presented here suggest that a detailed understanding of the mode of action of 2-halo-fatty acids as inhibitors of mammalian beta-oxidation will require consideration of the metabolic fate and inhibitory effects of both enantiomers. PMID- 8470911 TI - Developmental aspects of glucocorticoid regulation of polycyclic aromatic hydrocarbon-inducible enzymes in rat liver. AB - The expression of hepatic cytochrome P4501A1 (P4501A1), glutathione S-transferase Ya subunit (GST), and NAD(P)H:quinone oxidoreductase (QOR) proteins was evaluated in fetal, neonatal, and adolescent rats treated with 3-methylcholanthrene (MC) and the synthetic glucocorticoid dexamethasone (Dex) to elucidate the developmental aspects of glucocorticoid regulation of the induction of drug metabolizing enzymes by polycyclic aromatic hydrocarbons in vivo. These developmental states were chosen to represent either glucocorticoid deplete or replete conditions due to their differences in circulating glucocorticoid levels. Rats were treated with either MC (10 mg/kg body wt) or Dex (10 mg/kg body wt) or a combination of both and sacrificed 24 h later. In neonatal rats, the enzyme activities of P4501A1, GST, and QOR were increased by MC treatment approximately 65-, 1.4-, and 7-fold, respectively. The induction of these enzymes by MC was further potentiated an additional 2-, 1.5-, and 1.4-fold by concomitant Dex treatment. In adolescent male rats, Dex potentiated MC induction of P4501A1 activity (1.7-fold), but repressed MC induction of GST and QOR activities. When the protein contents for the three enzymes were measured by Western blot analyses, a positive correlation was observed with enzyme activities for all conditions except for the adolescent rat, where hepatic protein content of P4501A1 of rats treated with both MC and Dex was not significantly increased above the level seen with 3-methylcholanthrene treatment alone. The levels of specific mRNA and transcriptional activity for cytochrome P4501A1, GST Ya isozyme, and QOR closely paralleled the changes seen in their protein content in the livers of neonatal and adolescent rats. Dexamethasone potentiation of P4501A1 expression at the protein and RNA level were clearly statistically significant in the neonatal rat, but not in the adolescent rat, suggesting that the circulating levels of glucocorticoids are sufficiently low during the neonatal period that the full expression of induction of P4501A1 was not attained in the absence of exogenously administered glucocorticoids. These data also demonstrate that glucocorticoids have differential effects on the induction of GST Ya subunit and QOR protein and RNA in the neonatal and adolescent state, possibly related to circulating levels of glucocorticoids. PMID- 8470913 TI - [Present status of hyperthermia in Japan--emphasis on clinical research]. AB - A nationwide survey was conducted by the Japan Society of Hyperthermic Oncology (JSHO) to investigate the present status of hyperthermia in Japan. The results of survey and characteristic clinical research conducted in Japan are described here. 1) In Japan, 185 heating equipment units are in operation at 156 institutes. RF capacitive heating equipment accounts for 60%. 2) Records and registration are complete for 9,000 cases treated by hyperthermia. It is noteworthy that deep-seated tumors account for 60% of the total cases. 3) The percentages of different modalities are as follows: hyperthermia alone, 5.3%; thermoradiotherapy, 57.5%; thermochemotherapy, 22.6%; thermochemoradiotherapy, 14.5%. The present status of hyperthermia is well represented by these percentages. 4) The treatment schedule, indications, and treatment results are almost completely established for a combination of radiotherapy with hyperthermia. 5) Thermochemotherapy is performed at 70% of the surveyed institutes, who expect good treatment results. The JSHO organized a joint research team for thermochemotherapy, and present results are satisfactory. 6) Japan contributes much to the progress of the International Congress of Hyperthermic Oncology. The JSHO presents an ideal environment for research on hyperthermic oncology. PMID- 8470912 TI - [Retinoid signalling pathways]. AB - Retinoids, all-trans-retinoic acid (AT-RA) and its bioisters, exert diverse and profound effects on the growth and differentiation of normal and malignant cells, vertebrate development, and homeostasis. Since their nuclear receptors (RARs: alpha, beta and gamma) were cloned, extensive studies on retinoid signalling at molecular level have elucidated its elaborate mechanisms, by which the expression of a variety of retinoid responsive genes are regulated. Furthermore, discoveries of the second receptor system of retinoid (RXRs: alpha, beta and gamma) and their substantial ligand, 9-cis-retinoic acid (9C-RA), were recently reported. The heterodimer formation between RXR and RAR or other members of the steroid/thyroid hormone receptor superfamily gave us a new aspect of hormonal gene control including retinoids, thyroid hormone, vitamin D3 and others. These heterodimers were showed to bind specific response elements consisted of the direct repeat of consensus sequence (AGATTC) or its related sequences. Differential regulation of retinoid responsive gene by RARs or/and RXRs in vivo is an ongoing subject and the combinatory outcome of subtypes or isotypes of receptors, natural response elements, natural ligands (AT-RA, 9C-RA, or their metabolites) owing to pleiotropic effects of retinoids is being revealed. The anti-malignant effect of retinoids is another important theme. The report of prominent therapeutic effect of AT-RA against APL patients was sensational. In many APL patients, translocation between RAR alpha gene and an oncogenic gene, PML, can be detected, although the roles of their fusion products (RAR alpha-PML and PML-RAR alpha) in APL induction have not been understood. Furthermore, the cross-talk between RAR and AP-1 is thought to give an explanation for the suppressive effects of retinoids against tumor promoters (TPA and others). In those contexts, synthetic retinoids specific for each subtype of RAR or RXR, which will be useful reagents for biological studies and/or excellent therapeutic agents, are being developed. Some RAR subtype-selective compounds including antagonists have been already reported. PMID- 8470914 TI - [Technological progress in hyperthermia]. AB - In the early stage of hyperthermia, a large number of physical and engineering efforts have been done in the development or the improvement of the heating techniques. As matters stand, they were not always satisfied clinically. Thus even in this moment, clinical techniques of hyperthermia should be build up rapidly. This paper describes some of the highlights of ongoing physical researches to develop the clinical hyperthermia and to identify a trend of emerging physical systems available on hyperthermia. PMID- 8470915 TI - [Biological basis of thermochemotherapy]. AB - Interactive effects of combined treatment with hyperthermia and chemotherapeutic agents or chemical substances were interpreted in the experimental aspects of medical sciences. It was also interpreted how a physiological circumferential conditions in vivo influenced on thermosensitivities of cells, tissues or individuals. Among the physiological conditions, hypoxia and insufficient nutrition apparently enhance thermosensitivity while reduce radiosensitivity. Interactive effects in combined treatments with hyperthermia and alkylating agents varies among the alkylating agent adopted. DNA strand scission by alkylating agent is increased and repair of the DNA damage is suppressed in combination with hyperthermia. Almost all the antimetabolites and botanic alkaloids are reported to show no appreciable interactive effect in combination with hyperthermia. However, a sort of derivatives of mitotic toxins interacts with hyperthermia (unpublished data). Effects of anticancer antibiotics vary due to the variety of the mechanism of action of the antibiotics. Therefore, interactive effects of these antibiotics with hyperthermia also vary among the antibiotics. Most marked interaction with hyperthermia was shown in Mitomycin C, while the cell killing effect of Actinomycin D itself was reduced reportedly by the combined hyperthermia. Further development in thermophysiology may perform an extent of elevation in human whole body temperature. It has been considered internal heating may be more efficient than external heating for the hyperthermia alone. In the other hand, local heating can chemosensitize within the localized heated area where the blood concentration of anticancer drug is even, although variety of intervention could be devised to localize anticancer drug distribution. Variety of heating modalities and the apparatus would be developed which contribute for further interdisciplinary oncotherapy in near future. PMID- 8470916 TI - [Current status of thermoradiotherapy in cancer therapy]. AB - The current status of thermoradiotherapy for cancer is reviewed. The usefulness of this combined treatment for superficial tumors, in which heating and thermometry are relatively easy to apply, has been clearly demonstrated by many clinical results. With recent technological advancements, the application of thermoradiotherapy to deep-seated tumors is increasing, and encouraging results have been reported for various tumors including brain tumors, carcinomas of the breast, lung, esophagus, liver, rectum, urinary bladder, and soft tissue tumors. Thermoradiotherapy seems a very promising treatment modality for various refractory malignancies. PMID- 8470917 TI - [A new sequential chemotherapy of methotrexate with 5-fluorouracil against advanced colo-rectal cancer]. AB - A new sequential chemotherapy consisting of intravenous (IV) administration of methotrexate (MTX) 50 mg/m2 followed by 3 equal IV doses of 5-fluorouracil (5-FU) 500 mg/m2 at 1.4 and 21 hrs. and a leucovorin rescue (15 mg/body/8 hr) from 24 hrs. after MTX for 3 days was applied every two weeks for the patients with advanced colo-rectal cancer. The effectiveness of this MTX/3-dose 5-FU regimen was compared retrospectively with that of the standard sequential regimen consisting of the IV administration of MTX 100 mg/m2 followed by a single IV dose of 5-FU 800 mg/m2 one hr. later and a leucovorin rescue (21 mg/body/6 hr) 24 hrs. later given every week, namely MTX/1-dose 5-FU regimen. Partial response was achieved in 7 (46.7%) of 15 evaluable patients with the MTX/3-dose 5-FU regimen and in 3 (13.6%) of 22 evaluable patients with the MTX/1-dose 5-FU regimen (p < 0.05). The median survival times were 13 and 9 months, respectively. There were no significant difference in the patient characteristics between the two groups, and the toxic effects were much lower in the MTX/3-dose 5-FU than in the MTX/1 dose 5-FU regimen. It is therefore, concluded that the MTX/3-dose 5-FU regimen is superior to the standard MTX/1-dose 5-FU regimen. PMID- 8470918 TI - [Evaluation of the combination of chemotherapy with etoposide, adriamycin and cisplatin (EAP) in advanced or recurrent gastric cancer]. AB - EAP therapy was performed on 30 cases of advanced or recurrent gastric cancer between September 1987 and July 1991. The clinical responses of 15 trial patients were evaluated. The overall response rate was 40.0% (CR, one case; PR 5 cases). The results were thus not as favorable as that reported by Preusser et al. On the contrary, with such a poor response rate, this treatment did not lead to a prolonged life span (mean survival time; 5.6 months, median survival time; 4 months). Side effects, such as myelosuppression, appetite loss, nausea, vomiting, liver dysfunction, renal dysfunction, and alopecia, were also observed. Myelosuppression was a dose-limiting factor. The rhG-CSF proved in 4 cases to be a clinically useful tool against the neutropenia induced by this treatment. It may be concluded that EAP should be given to the following selected patients: (1) those whose condition is not so far advanced: (2) those who have not received many other forms of treatment; and (3) those in excellent general physical condition. PMID- 8470919 TI - [Antitumor activity of a new antiestrogenic drug, toremifene (NK622) against human breast cancer xenografts in nude mice]. AB - NK622, a novel tamoxifen(TAM) analog with nonsteroidal structure is an antiestrogenic drug with less toxicity compared with that of TAM. We studied the in vivo antitumor activity against human breast cancer xenografts in nude mice. NK 622 significantly inhibited the growth of estrogen-dependent Br-10 breast cancer but not inhibited the growth of estrogen-independent MC-2-JCK and MC-5-JCK when orally administered once daily for 14 days at the maximum tolerated dose (200mg/kg/day). The dose of NK622 in animal studies was calculated by measuring plasma level in patients receiving 40 mg/body/day oral treatment and clinically equivalent dose (CED) was determined. At the calculated CED, NK622 significantly inhibited the growth of Br-10. These results indicate that NK622 is a promising drug comparable to TAM because of the growth inhibition of estrogen-dependent breast cancers. PMID- 8470920 TI - [Effect of medroxyprogesterone acetate on the anticellular activity of 5 fluorouracil against human breast and stomach cancer cells]. AB - As 5-fluorouracil (5-FU) has been known to show clinically antitumor effects against both breast and stomach carcinomas. We compared the combined effects of medroxyprogesterone acetate (MPA) with 5-FU on the growth of cultured human breast and stomach carcinoma cells. MPA inhibited the growth of estrogen dependent human breast carcinoma MCF-7 cells at the low concentrations and exhibited an additive effect in combination with 5-FU. MPA also inhibited the growth of human stomach carcinoma MKN-45 cells at relatively high concentrations and exhibited an additive effect in combination with 5-FU. Human stomach carcinoma MKN-28 cells were rather insensitive to MPA, but, an additive combination effect of MPA and 5-FU was observed. These three cell lines were found to have MPA-binding proteins which may be distinct from the nuclear progesterone receptor, suggesting the correlation with growth-inhibitory activity of MPA. PMID- 8470921 TI - [Pharmacokinetics and antitumor activity of MX2, a new morpholino anthracycline in brain tumor intracerebral transplanted in rats]. AB - Pharmacokinetics and antitumor activity of MX2.HCl (MX2), a new morpholino anthracycline, were investigated in rats transplanted 9L gliosarcoma cells in the brain. (1) Pharmacokinetics: AUC of MX2 in the brain tumors which received intracarotid and intravenous injection of 2mg/kg of MX2 were 117.50 and 55.94 micrograms.hr/g, respectively. AUC of the brain tissue was 1.38-3.90 micrograms.hr/g. (2) Antitumor activity: The inhibition of cell growth at the concentration of 0.1 micrograms/ml was 73.1% with MTT assay. The mean survival time in tumor-bearing rats after intracarotid and intravenous injection of 2mg/kg of MX2 prolonged significantly. Therefore, it seems that MX2 will become an efficacious drug for the treatment of malignant glioma. PMID- 8470922 TI - [Evaluation of long-term administration of oral anti-cancer agent]. AB - To evaluate the effectiveness of surgical adjuvant chemotherapy, we attempted to determine whether cancer patients were taking oral anticancer agents properly. Tegafur or UFT was administrated orally to patients with gastric or colorectal cancers after surgery for at least a year. There were 19 gastric cancer patients and 18 colorectal cancer patients. Serum levels of Tegafur and 5-FU were measured every three months. Results of the study showed that all the patients took medicine regularly according to the prescription and serum 5-FU levels of most patients (75%) exceeded the minimal effective serum level. PMID- 8470923 TI - [A case of advanced gastric cancer responding to an FAP (5-FU, ADM, platinum compounds) combined chemotherapy]. AB - An experience with an advanced gastric cancer patient with metastases to bilateral breasts, uterus, abdominal lymph nodes, bilateral axillary and supraclavicular lymph nodes, and bone marrow, responded extremely well to an FAP combined chemotherapy as reported here. The patients received four courses of 5 FU (370 mg/m2/day, for five days, continuous infusion), ADM (30 mg/m2 on day 1, i.v.) and CDDP (55 mg/m2 on day 1, i.v.) every 3 weeks in our hospital. This was followed by 7 months of outpatient therapy with 5-FU (550 mg/m2 on day 1, i.v.), ADM (30 mg/m2 on day 1, i.v.) and CBDCA (330 mg/m2 on day 1, i.v.) for every 4 weeks. The complete remission of the primary and metastatic lesions, that was confirmed by the histological examinations, was obtained after 10 months since the initial treatment started. The toxicity was generally moderate, however, the alopecia was severe. The patient has been living for 6 months without any signs of the recurrence after the complete remission obtained. PMID- 8470924 TI - [A case report of adenosquamous cell carcinoma of the stomach responding well to combination chemotherapy]. AB - A 51-year-old man with unresectable adenosquamous cell carcinoma classified Borrmann type 3 of the stomach was treated with combination chemotherapy. The treatment consisted of two parts: intraabdominal administration of CBDCA (400 mg/body) during the operation, and transcatheteral intraabdominal infusion of CDDP(100 mg/m2) on day 1 and oral administration of UFT (400 mg/m2) on day 1 to 28 from a month after the operation. The latter therapy was performed every four weeks, and was administered two times. Primary gastric region was improved like a type II-C endoscopically, and metastatic lymphnode measuring 5 cm diameter disappeared on a computed tomography after the treatment. Thus, total gastrectomy was performed. No cancer cells were shown in both the resected stomach and dissected lymphnodes upon histological examination. Generally, patients with unresectable gastric cancer have a poor prognosis. But we concluded that the survival time and the quality of life in this patient were remarkably improved by the effective combination chemotherapy. PMID- 8470925 TI - [A case of gastric cancer with multiple liver metastases showing marked efficacy of preoperative and postoperative chemotherapy with CDDP, MMC and UFT(PMU), or CDDP, MMC, UFT and etoposide (PMUE)]. AB - The patient, a 65-year-old male with far advanced gastric cancer of H3N4 (Stage 4), was assumed inoperable on admission and chemotherapy using CDDP, MMC and UFT(PMU) was carried out. As a result, the levels of AFP and CEA were reduced notably, and PR effects were recognized in liver and lymphnode metastatic lesion. Thus, 2 months later, reduction surgery was performed, during which primary lesion was resected and a reservoir tube for chemotherapy was placed in the common hepatic artery. Subsequently, the chemotherapy with Etoposide added to PMU(PMUE) was continued by utilization of a reservoir, so that liver metastasis decreased more than 90% from the maximum. However, metastasis lesions of left lobe of the liver had enlarged with reincrease of AFP and CEA since 6 months after the operation. A month later left lobectomy of the liver was performed. Residual metastases of the liver were then enlarged. PMUE with Ca antagonist was used with little effect then. The patient died of liver failure 15 months after initial admission. PMID- 8470926 TI - [A infant case of rhabdomyosarcoma arising from the left iliac region with complete remission for 2 years after combination therapy]. AB - A case of rhabdomyosarcoma in a 14-year-female is reported herein. The patient developed left inguinal pain and tumor. She was initially seen by her local medical doctor, who biopsied her left inguinal tumor with a pathological report of malignancy. She was referred to the Ryukyu University Hospital in July, 1990. CT and MRI demonstrated a large tumor 10 cm in diameter arising from the left iliac region. The tumor was extirpated and the pathological report indicated rhabdomyosarcoma (alveolar type). The patient was treated with VAC chemotherapy and local irradiation. Her course has been uneventful for the past 2 years without any clinical manifestation of recurrence since surgery. PMID- 8470927 TI - [A case of advance colon cancer responding to sequential methotrexate and 5 fluorouracil therapy]. AB - A 60-year-old female was diagnosed by X-ray examination and endoscopy as ascending colon cancer. Ultrasonography and computed tomography revealed two metastatic tumors in the liver. Abdominal surgery revealed peritoneal disseminations, massive lymph node metastasis and direct invasion of the transverse colon and ileum. From pathological examination the diagnosis was moderately differentiated adenocarcinoma. After right hemi-colectomy, sequential methotrexate and 5-fluorouracil therapy as well as oral administration of UFT, liver metastasis disappeared and no sign of ascites was found in this case. Complete response time was over 8 months. There have been no severe complications. PMID- 8470928 TI - [Etoposide, pirarubicin and cisplatin(ETP) combined therapy of inoperable head and neck cancer]. PMID- 8470929 TI - [Molecular mechanism of carcinogenesis]. AB - Biological characteristics of cancer cells are thought to be immortalization, transformation (abnormal cell growth) and capacity for tumor invasion and metastasis. Recent studies have revealed that many cellular genes (oncogenes and anti-oncogenes) were activated or suppressed at the level of DNA in cancer cells, and in normal condition the products of these genes have important roles in signal transduction for cell growth as a positive or negative way. Point mutation and unphysiological DNA recombination are considered to be major molecular mechanisms in the alteration of these cellular genes. Further, several genes were found to be involved in invasion and metastasis. However, still a significant portion of cancers remains to be elucidated in terms of unknown cellular (or viral) genes involved in multi-step carcinogenesis. Therefore, we need to continue the basic research on cancer and to initiate the studies on new chemicals, hormones or others by which we could control the activities of known oncogene and anti-oncogene products. PMID- 8470930 TI - Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp- +/+ mice. AB - The deposition of immunoglobulin (Ig) at the dermo-epidermal junction (DEJ) of the skin, frequently observed in autoimmune mouse strains, is similar to that seen in patients with systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr (MRL/lpr) mice have an autosomal recessive mutant gene, lpr, which produces massive T-cell proliferation and accelerates the onset of autoimmune diseases. MRL/Mp- +/+ (MRL/n) mice lack the lpr gene, and do not develop autoimmune disease during the first year after birth under pathogen-free conditions. To verify the mechanisms of subepidermal Ig deposition in the skin of LE, we designed an experiment in which we could induce Ig deposition in the control MRL/n mice. Intraperitoneal injection of lymphoproliferative cells of aged MRL/lpr mice induced splenomegaly and splenic granulomatous angitis in the control MRL/n mice. Lipopolysaccharide (LPS), a polyclonal B-cell activator, induced slight splenomegaly and relatively high levels of serum Ig. Dermatopathological investigation revealed mild lymphocyte infiltration without positive Ig deposition at the DEJ of MRL/n mice treated with proliferative T cells. Injection of both proliferative T cells and LPS induced 50% positivity of subepidermal Ig deposition, and high levels of serum immunoglobulins and anti-double stranded DNA (anti-dsDNA) antibodies. These changes were not observed in MRL/n mice injected with thymocytes of newborn MRL/lpr mice. Skin lesions and lupus nephritis were not demonstrated in any of the mice tested. This study suggest that both the mild inflammatory reaction and the presence of anti-dsDNA antibodies are required for the induction Ig deposition at the DEJ in the skin of LE patients. PMID- 8470931 TI - Potent debriding ability of collagenolytic protease isolated from the hepatopancreas of the king crab Paralithodes camtschatica. AB - The debriding activity of the protease complex produced from the hepatopancreas of the king crab Paralithodes camtschatica was evaluated in vivo. The results clearly showed that the crab preparation had a high debriding ability. Individual proteases were isolated chromatographically from the crab complex to compare their debriding activities. All the purified proteases were active in vivo. The most active component of the complex was the isozyme C of crab collagenolytic protease, a member of the chymotrypsin-like protease class. PMID- 8470932 TI - Pachyonychia congenita (Jadassohn-Lewandowsky syndrome)--evaluation of symptoms in 36 patients. PMID- 8470933 TI - Immunohistochemical detection of oestrogen receptor-related protein (p29) in apocrine glands. PMID- 8470934 TI - Boron, molybdenum, and selenium in aquatic food chains from the lower San Joaquin River and its tributaries, California. AB - Boron (B), molybdenum (Mo), and selenium (Se) were measured in water, sediment, particulate organic detritus, and in various biota--filamentous algae, net plankton, macro-invertebrates, and fishes--to determine if concentrations were elevated from exposure to agricultural subsurface (tile) drainage during the spring and fall 1987, in the San Joaquin River, California. Concentrations of B and Se, but not Mo, were higher in most samples from reaches receiving tile drainage than in samples from reaches receiving no tile drainage. Maximum concentrations of Se in water (0.025 microgram/mL), sediment (3.0 micrograms/g), invertebrates (14 micrograms/g), and fishes (17 micrograms/g) measured during this study exceeded concentrations that are detrimental to sensitive warmwater fishes. Toxic threshold concentrations of B and Mo in fishes and their foods have not been identified. Boron and Mo were not biomagnified in the aquatic food chain, because concentrations of these two elements were usually higher in filamentous algae and detritus than in invertebrates and fishes. Concentrations of Se were lower in filamentous algae than in invertebrates and fishes; however, concentrations of Se in or on detritus were similar to or higher than in invertebrates and fishes. These observations suggest that high concentrations of Se accumulated in invertebrates and fishes through food-chain transfer from Se enriched detritus rather than from filamentous algae. PMID- 8470935 TI - Effects of pentachlorophenol-contaminated food organisms on toxicity and bioaccumulation in the frog Xenopus laevis. AB - Sub-adult African clawed frogs (Xenopus laevis) were fed pentachlorophenol (PCP) injected mealworms containing 64.8 to 2604 ug of PCP per gram of worm for 27 days. There was no mortality and no significant bioaccumulation of PCP in the frogs. After three weeks, frogs fed 2,604 micrograms/g of PCP ceased eating. The no observed adverse effects level (NOAEL) based on significantly reduced food consumption (PCP-injected mealworms) was 638 micrograms/g. This corresponded to a NOAEL based on PCP intake of about 8 micrograms PCP/g frog/day. A toxicity threshold model estimated that about 800 micrograms/L of waterborne PCP may be a threshold for adverse effects in Xenopus or similar amphibians. Further study is needed to verify threshold estimates. PMID- 8470936 TI - Subchronic toxicity of aniline hydrochloride in rats. AB - Hematological, biochemical and histopathological responses of subchronic exposure to aniline hydrochloride (AH) have been investigated in rats. Male Sprague-Dawley rats were given 600 ppm of AH in drinking water while the control rats received tap water only. Five rats from each group were sacrificed at 30, 60, and 90 days of treatment. Organ-to-body weight ratio for spleen in the AH-treated rats was 56, 61, and 53% higher than controls at days 30, 60, and 90, respectively. Liver showed a biphasic pattern for this ratio, a decrease at 30 days and then an increase at 60 days. Among other organs, testes showed a significant decrease in this ratio at 60 days. Hematological analysis showed 65% increase in WBC counts at 30 days in the AH-treated rats, whereas, no changes were recorded at later time points. Erythrocyte counts in the AH-treated rats showed very significant decreases at all the time points, whereas, hemoglobin and hematocrit decreased at 30 and 90 days of treatment. Mean corpuscular volume and mean corpuscular hemoglobin increased in the AH-treated rats at 60 and 90 days of treatment. Methemoglobin content showed significant increases of 89, 59 and 45% at days 30, 60, and 90, respectively. Among serum immunoglobulins, IgA in the AH-treated groups showed 24 and 51% increases at days 60 and 90, respectively. Analysis of splenic lymphocyte subpopulation showed a decrease in the T-helper (CD4+/CD8-) sub-set at 90 days whereas, other subpopulations were not affected. Aniline hydroxylase activity in the liver microsomes of the AH-treated rats was significantly higher at 60 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470937 TI - Effect of nitrite on ureagenesis and carbohydrate metabolism in isolated rat hepatocytes. AB - The effect of three NaNO2 concentrations (0.5, 2.0, and 5.0 mM) on 15N-ammonia utilization, ureagenesis, glucose, pyruvate and lactate formation and glycogen breakdown were studied in isolated rat hepatocytes. Nitrite failed to affect the rate of glycogenolysis as well as the lactate and pyruvate formation, but at the same time it markedly increased the glucose formation. It is concluded that the increase in the glucose formation results from the nitrite stimulation of the rate of gluconeogenesis. An increased sodium nitrite concentration caused a significant decrease in the ammonia utilization and urea synthesis; there are strong linear correlations between the nitrite concentration and the amount of utilized ammonia (r = -0.93) and the formed urea (r = -0.96). The observed lower rate of ureagenesis in the presence of nitrite resulted from the diminished incorporation of the added 15N-ammonia into urea, as well as from the diminished urea formation from endogenous nitrogen. It is concluded that the disturbances in carbohydrate and nitrogen metabolism observed in the nitrite-poisoned animals are attributed to the direct effect of nitrite on metabolism. PMID- 8470938 TI - Levels of five mycotoxins in grains harvested in Atlantic Canada as measured by high performance liquid chromatography. AB - An analytical protocol using high performance liquid chromatography (HPLC) was used to analyze samples of spring wheat, winter wheat, 2-row barley, and 6-row barley over a period of three years for the presence of five mycotoxins. These included deoxynivalenol, zearalenone, T-2 toxin, HT-2 toxin, and diacetoxyscirpenol. The protocol employed a single extraction step using acetonitrile-water and two cleanup procedures. One utilized a solid-phase extraction column and the other a charcoal-alumina column. Detection limits ranged from 0.02 to 0.15 micrograms of mycotoxin g-1 grain. Little T-2 toxin, HT 2 toxin, or diacetoxyscirpenol was found in the samples. Deoxynivalenol was detected in 53 to 62% of the samples tested and zearalenone in 25-29% of the samples. Several enzyme-linked immunosorbent assays were used for comparison purposes with deoxynivalenol, zearalenone, and T-2 toxin. These kits provided reliable qualitative, but not quantitative, data. PMID- 8470939 TI - Statistical andrology: standard semen analysis and computer-assisted sperm motility analysis. AB - Results are reported of a statistical evaluation of the variables obtained by standard microscopic semen analysis and by computer-assisted sperm motility analysis. Descriptive statistical analysis and cluster analysis were carried out on both sets of data. A contingency table was created to compare the classifications obtained by the two clustering procedures. A canonical correlation analysis was performed to evaluate the classification power of the variables obtained by the two semen analyses. The results show that the two techniques of semen analysis are complementary and not substitutive and that the correlated variables "percentage forward motility" and "sperm velocity" are the most discriminating. PMID- 8470940 TI - Hypoosmotic swelling test with a medium of distilled water. AB - The functional competence of the human sperm membrane is assessed by studying the swelling reaction of sperm when suspended in a medium of distilled water (water test). Eighty-seven patients with idiopathic infertility were investigated by the water test and the results were compared with various semen parameters. High correlations with the percentage of b-g type swollen sperm in the water test were observed for sperm concentration (r = .53, p < .05) and percent motility (r = .62, p < .01). The sperm swelling values obtained by the water test correlated well with those obtained by the hypoosmotic swelling test (HOST). Correlation coefficients in b-g and g swelling pattern were 0.89 and 0.71, respectively. The percentage of g-type swelling obtained by the water test was significantly larger than that obtained by the HOST (p < .05), although the two hypoosmotic procedures gave similar percentages of b-g swelling pattern. The percentage of g swelling pattern obtained by the water test correlated well with percent motility (r = .70, p < .001). These findings suggest that the water test is more useful for assessing the integrity of the sperm membrane than the HOST. The relationship between this test and subsequent fertility, as well as to other sperm function tests, needs further investigation. PMID- 8470942 TI - Hypoosmotic swelling: evaluation of sperm tails using strict criteria in cases of globozoospermia. AB - The semen from two men with globozoospermia was evaluated for hypoosmotic swelling changes and morphologic evaluation of the tail using strict criteria. No abnormalities were noted. Globozoospermia is due to a genetic defect that results in the absence of acrosomal structures. The acrosomal vesicle in the Golgi region does not develop in close contact to the nucleus, which results in the formation of globe-shape heads. Although some semen parameters were abnormal in both cases, they were different types, suggesting no association with round-headed sperm. PMID- 8470941 TI - Serum and urinary levels of pituitary--gonadal hormones in insulin-dependent and non-insulin-dependent diabetic males with and without neuropathy. AB - Diabetic neuropathies were studied in 100 insulin-dependent diabetes mellitus patients, 314 non-insulin-dependent diabetes mellitus patients with and without an objective evidence of neuropathy (age span, 15-80 years; duration of diabetes distributed over 1-33 years), and their age-matched nondiabetic controls. Serum and urinary levels of pituitary-gonadal hormones were evaluated in the diabetic subjects. There were striking results, i.e., a significantly low serum total and serum free (urinary) testosterone level (p < .0005) and a significantly high serum and urinary FSH and LH and serum prolactin level (p < .0005), specifically in the neuropathic diabetic patients, suggesting a series of pathological reactions in the smooth musculature of genital organs characterized by an increase in the interstitial thickness of seminiferous tubules, peritubular and intertubular fibrosis, and tubular sclerosis. Testicular necrosis, probably due to neuropathy, provided an additional aid to confirm these findings. A decrease in semen volume and sperm motility in the diabetic neuropathic patients further suggested the involvement of the entire smooth musculature of the reproductive tract, leading to atonia of the bladder and urethra. Such complications are purely neurogenic. The low serum and urinary testosterone levels and increased serum and urinary FSH and LH and serum prolactin levels in the diabetic men with neuropathy suggest gonadal disorder (hypogonadotropic hypogonadism), which may be due to testicular necrosis and thickening of seminiferous tubules, causing autonomic lesion. PMID- 8470943 TI - Effectiveness of calcium and magnesium on testicular sulfatase activity. AB - Nucleotides and calcium ions have been implicated in the regulation of biosynthesis of steroids, although the exact locus of calcium activity is not yet known. The administration of Ca2+ to Leydig cells increases testosterone production. Steroid sulfatase activity is reported to be enhanced by adenine nucleotides. In the present study the testicular sulfatase was evaluated in subcellular fractions by conversion of sulfate to free steroids in the presence or absence of Ca2+ and Mg2+ ions. The specific activity of the enzyme, which was located predominantly in submitochondrial fraction, showed a positive correlation with calcium, increasing 1.5-fold in the presence of 2.54 mM of calcium (62 nmol/h mg protein-1). In contrast, magnesium inhibited the enzymatic activity 1.79-fold in presence of 1.18 mM (23 nmoles/h mg protein-1). It would appear that testicular sulfatase is predominantly located in the mitochondria, which is recognized as one of the major sites of control of intracellular metabolism, and that its enzymatic activity could be modulated by calcium regulating the levels of potentially active androgens. PMID- 8470944 TI - Anatomical characteristics of the left testicular venous system in man. AB - Autopsy was performed on 49 male cadavers and the entire course of the left testicular vein (LTV) was studied. The testicular venous pathway was divided into four levels: scrotal, inguinal, pelvic, and lumbar. At the scrotal level, many small testicular veins constituting the pampiniform plexus showed various anastomoses with the cremasteric and vasal veins. At the inguinal and pelvic level, 4-12 and 2-8 LTVs were recognized, respectively. At the pelvic level, absence of valves was seen in 33% of the cases. At the lumbar level, 1-5 LTVs were observed and were mainly anastomosed with the retroperitoneal, ureteral, and kidney capsular veins. Absence of valves at the lumbar level was seen in 37% of the cases. In 11 cases, the valves that were present were incompetent. The presence of more than one LTV at the lumbar level indicates the necessity for attentive identification of all of the testicular veins during surgical treatment of varicocele. PMID- 8470945 TI - Effects of an inhibitor of adenylate cyclase on acrosome reaction induced by protein kinase C activators. AB - To determine whether the adenylate cyclase and the protein kinase C pathways act independently to modulate the human sperm acrosome reaction, we studied the effects of 2'-O-methyladenosine (adenylate cyclase inhibitor) on acrosome reactions induced by protein kinase C activators (phorbol diesters and synthetic diacylglycerols) or an adenylate cyclase stimulator (forskolin:FR). Fifty aliquots of capacitated spermatozoa were divided into 5 groups (A, B, C, D, and E), each containing 10 samples. One control aliquot (CN) and five experimental aliquots (EX1, EX2, EX3, EX4, and EX5) were prepared from each sample. Phorbol 12 myristate, 13-acetate (PMA, 10 mumol/L), 4 beta-phorbol 12,13-didecanoate (PDD, 0.1 mumol/L), 1-oleoyl-2-acetyl-sn-glycerol (OAG, 50 mumol/L), 1,2-dioctanoyl-sn glycerol (DOG, 50 mumol/L), or FR (10 mumol/L) was added to each of the experimental aliquots in groups A, B, C, D, and E, respectively. Increasing concentrations of 2'-O-methyladenosine were added to aliquots EX2, EX3, EX4, and EX5. After an incubation period of 25 min at 37 degrees C, it was found that the percentage of acrosome-reacted spermatozoa (%ARS) was significantly and dose dependently decreased by 2'-O-methyladenosine concentrations of 1 mM or more. Within each group, the %ARS was significantly higher in EX1 aliquots than in CN aliquots. The reduction of acrosome reactions induced by protein kinase C activators by the adenylate cyclase inhibitor suggests that the protein kinase C pathway interacts with the adenylate cyclase pathway to modulate the human sperm acrosome reaction. PMID- 8470946 TI - Hormone profiles and contralateral testicular histology in Down's syndrome with unilateral testicular tumor. AB - Hormonal profiles and testicular histology were studied in two patients with Down's syndrome with unilateral testicular tumor. Plasma levels of LH and FSH were elevated above normal ranges in both cases. In case 1, plasma testosterone level was abnormally low, but prolactin level in plasma was within the normal range. Case 2 showed elevated concentration of plasma prolactin and normal level of plasma testosterone. The administration of LH-RH resulted in low response of plasma gonadotropins. The response of plasma testosterone to the administration of HCG was abnormally suppressed in both cases. Testicular histology showed reduction of Johnsen score count and tubular diameter, and an increase in wall thickness. These results indicated that male patients with Down's syndrome have an abnormality in hypothalamo-pituitary-gonadal axis. PMID- 8470947 TI - Male reproductive system in patients exposed to ionizing irradiation in the Chernobyl accident. AB - Twelve men with different forms and stages of chronic radiation dermatitis caused by accidental exposure to beta and gamma irradiation during and after the Chernobyl atomic power plant accident were examined. Two patients had impotentia coeundi, and the others reported various impairments of sexual function. One patient had aspermia, two patients had azoospermia, one had oligospermia, and four had normal sperm counts. In three samples abnormal forms of spermatozoa were increased. Sperm motility was decreased in 3 samples and was normal in another. Hormonal analyses demonstrated low testosterone plasma levels in two patients, an increase of follicle stimulating hormone (FSH) levels in six patients, and a decrease of luteinizing hormone (LH) in one patient. In one patient who showed an increase of plasma prolactin level, associated with low testosterone and LH, a microadenoma of the pituitary gland (prolactinoma) was detected. It would appear that there is an association between accidental exposure to ionizing radiation of varying severity and the impairment of exocrine and endocrine testicular function, sometimes resulting in long-lasting physiological and psychological problems. PMID- 8470948 TI - Evolution of the Drosophila melanogaster-sigma virus system in natural populations from Languedoc (southern France). AB - An analysis of natural populations of Drosophila melanogaster in a southern French region (Languedoc) was started in 1983, concerning two non Mendelian systems: the P-M system of transposable elements and the sigma virus. This virus is not contagious, but only transmitted through gametes; it is usually present in a minority of individuals in natural populations. The first data collected revealed unexpectedly clear and fast-evolving phenomena; they also gave evidence of some interesting correlations between the two systems. This paper presents all the results gathered from 1983 to 1991 in the Drosophila-sigma system. Striking correlations were observed for three interconnected parameters: frequency of infected flies, frequency of an allele of the fly giving resistance to the virus, and adaptation of the virus to this allele. This adaptation consisted of a qualitative step (change of viral type) followed by quantitative variation (better adaptation to the allele). This analysis also showed, firstly, that the evolution of natural populations differs completely in Languedoc from the rest of France; secondly, that three geographical zones where selective forces worked differently persisted over time in Languedoc. PMID- 8470949 TI - Polypeptide synthesis induced in Nicotiana clevelandii protoplasts by infection with raspberry ringspot nepovirus. AB - Infection of Nicotiana clevelandii protoplasts by raspberry ringspot nepovirus resulted in the accumulation of about 24 polypeptides that differed in M(r) and pI from polypeptides accumulating in mock-inoculated protoplasts. Similar polypeptides accumulated in protoplasts infected with the S and E strains of RRV but different infection-specific polypeptides were detected in protoplasts infected with tobacco ringspot nepovirus. The M(r) of RRV-specific polypeptides ranged from 210,000 to 18,000 and most are presumed to be derived from others by proteolytic cleavage. No evidence was found for marked changes in polypeptide abundance with time after inoculation or for any virus-specific polypeptide becoming disproportionately abundant in the medium during culture. PMID- 8470950 TI - Direct sequencing of genomic cDNA fragments amplified by the polymerase chain reaction for molecular epidemiology of dengue-2 viruses. AB - A nucleotide fragment encoding amino acids 29 to 94 in the E-protein of 28 dengue 2 isolates of diverse geographic and host origins was examined by direct sequencing of a polymerase chain reaction (PCR)-amplified product, and compared to six previously published sequences. Nucleotide divergence ranged from 0 to 19.8% corresponding to a maximum of 9% divergence in the amino acid sequence. Taking a divergence of 6% between the nucleotide sequence as a cut off for genotype classification, six groups have been established. Southeast Asian and the Jamaican 1983 genotypes show a high rate of similarity (> 95.2%). Our results suggest that virus of this group is now circulating as the dominant topotype in Brazil (1990) and in French Guyana (1986-1991). African strains fall into two groups, one endemic group (1970-1990) and one epidemic group (1986-1987). The three other groups correspond to viruses from Sri Lanka (1982) and the Seychelles (1977), from Puerto Rico (1973) and from Tahiti (1975). Our approach appears to be valuable characterizing dengue isolates, easily and rapidly. PMID- 8470951 TI - African swine fever virus specific porcine cytotoxic T cell activity. AB - African swine fever virus (ASFV) specific, cytotoxic T lymphocyte (CTL) activity has been studied in a protection model in which SLA inbred miniature swine are experimentally inoculated with a naturally occurring, non-fatal ASFV isolate (NHV). Peripheral blood mononuclear cells (PBMC) from such infected swine show significant activity in CTL assays, using cultured ASFV-infected porcine blood derived macrophages as target cells. This CTL activity is elicited from PBMC by in vitro restimulation of effector cells with low doses (multiplicity of infection = 0.1) of the homologous virus isolate for 48 to 72 h. For SLAc/c effectors, this CTL activity appears to be SLA class I restricted because (1) blocking target cell antigens with monoclonal antibodies (mAb) against SLA class I antigens causes a major reduction in CTL activity; (2) there is preferential lysis of SLA class I matched, ASFV infected targets; and (3) depletion of effector cells with CD8 specific mAb and complement causes a reduction in CTL activity. The CTL activity is ASFV specific for all pigs tested in that infected macrophages are preferentially lysed as compared to normal (non-infected) cultured macrophages or macrophages infected with hog cholera virus (HCV). Lysis of macrophages infected with different ASFV isolates revealed that there is marked lysis of macrophages infected with the virulent L60 isolate but less lysis of macrophages infected with the DR-II and Tengani isolates. In summary, our data show that ASFV specific CTL activity is triggered in swine infected with the NHV ASFV isolate. PMID- 8470952 TI - Dolphin morbillivirus infection in different parts of the Mediterranean Sea. AB - Morbillivirus were isolated from Mediterranean striped dolphins (Stenella coeruleoalba) dying along the coasts of Italy and Greece in 1991. They were antigenically identical to the morbilliviruses isolated from striped dolphins in Spain in 1990. PMID- 8470953 TI - Exchange of the cellular growth medium supplement from fetal bovine serum to Ultroser G increases the affinity of adenovirus for HeLa cells. AB - A comparative investigation was performed on the process of attachment of adenovirus type 2 to HeLa cells cultivated in the presence of 3.5% fetal bovine serum (FBS-cells) or 2% Ultroser G (USG-cells). The initial rates of virus attachment were markedly higher at temperatures between 10 and 35 degrees C for the virus binding to USG-cells than to FBS-cells. This was not caused by a higher amount of available virus-recognizing cellular receptor sites or cellular receptor units recognizing the viral fiber, but could be explained by a higher affinity of virions for USG-cells as compared to FBS-cells. Studies of virus attachment to cells, pretreated with neuraminidase and/or wheat germ agglutinin, suggested that the cellular receptor sites of FBS-cells were masked to a higher extent by sialic acid than the cellular receptor sites of USG-cells. PMID- 8470954 TI - Enhancement of intracellular uncoating of adenovirus in HeLa cells in the presence of benzyl alcohol as a membrane fluidizer. AB - The early extra- and intra-cellular interaction between adenovirus type 2 and HeLa cells was studied in the presence of benzyl alcohol as a fluidizing agent. The process of virus attachment and internalization were not affected at 5-15 mM of benzyl alcohol at 25 degrees C. Under the same conditions an enhancement by 45% at the most was demonstrated for the cell-mediated virion uncoating. By completely blocking virion internalization with 50 mM azide the uncoating was reduced to 20% of the normal level. The remaining surface-located uncoating was not affected by benzyl alcohol. It was demonstrated that an enhancement of the intracellular virion uncoating was followed by a raised production of the hexon antigen, which was interpreted as an increase in the specific infectivity of the virus. PMID- 8470955 TI - Sequence of the NS 1 gene of the K 23 isolate of tick-borne encephalitis virus and identification of conserved motifs. AB - The NS 1 gene from the K 23 isolate of tick-borne encephalitis virus has been sequenced. The NS 1 gene sequence, and many structural features of the NS 1 protein are heavily conserved. Six conserved peptides were also identified. PMID- 8470956 TI - Possibility of reinfection after immunisation with RA27/3 live attenuated rubella virus. AB - A serological study was carried out on 527 girls immunized with RA 27/3 rubella vaccine. Data from all scheduled serum samples over a 5-year follow-up were available for 102 vaccinees, 10 (9.8%) of whom showed evidence of reinfection during the 5th year after immunisation, a year in which there was a rubella outbreak in the Siena area (Italy). We examined in greater detail the serological responses of these vaccinees after reinfection and the consequent implications pertinent to the duration of the protective immunity. PMID- 8470957 TI - Nucleotide sequence of the coat protein gene of pelargonium leaf curl virus and comparison of the deduced coat protein amino acid sequence with those of other tombusviruses. AB - The sequence of 1,787 nucleotides (nts) in the genomic RNA of pelargonium leaf curl virus (PLCV) was determined. It included the entire coat protein (cp) gene (nts 585 to 1,754), 558 nts of the 3' end of the putative RNA polymerase gene, 26 nts of an intercistronic region between the two genes and 33 nts downstream of the stop codon of the cp gene. The cp gene was cloned into the expression vector pET8c and expressed in E. coli. The deduced cp amino acid sequence of PLCV was compared with those of five other tombusviruses. The closer the degree of serological relatedness between two viruses, the more similarity was found in their cp amino acid sequences not only in the protruding domains, but also in their random and shell domains and in the arm regions. Nucleic acid hybridization tests, cp amino acid comparisons and serological tests all suggest the same order of sequence for the relationships in the tombusvirus group. PMID- 8470958 TI - Pathogenesis of HSV-1/2 induced vaginitis/vulvitis of the mouse: dependence of lesions on genetic properties of the virus and analysis of pathohistology. AB - A scoring system for herpes simplex virus (HSV) induced vaginitis/vulvitis in Balb/c mice was delineated from vaginal infections. Four degrees of vaginitis/vulvitis could be distinguished after infection with suitable strains of HSV despite nearly identical replication rates. The time course of replication, inflammation and pathohistology was compared further. Grade 0 was defined by lack of symptoms despite presence of strong replication, which was detectable at days 3-6. Focal necrotic lesions of the epithelial layer were present containing HSV-specific antigens. DNA could be detected by hybridization only in the outer zone of these areas. At day 6 these zones began to be re epithelialized. In the vaginal lumen abundant detached epithelial cells and granulocytes were already present by day 2. Grade 1 was macroscopically characterized by a slight inflammation commencing on days 5-6. Replication and antigens in the epithelium were found on days 2-6. HSV-antigens were only detected above the basal membrane, and some infiltration with granulocytes and lymphocytes was observed below the basal membrane at day 4. Grade 2 showed strong redness and inflammation as well as hyperemia. Cellular infiltrates were present in the large antigen containing epithelial lesions and below the basal membrane. From day 4 on, neurons were HSV-antigen and DNA positive and macrophages in the stroma contained antigen. The vulva was also shown to be involved. Grade 3 exhibited prolonged severe hyperemia, and destruction of the epithelium and the stroma with necrosis and infiltration, especially of the vulva. This grading system was shown to depend on certain unknown genetic properties of HSV-strains. Neither thymidine-kinase activity, replication in macrophages, fusion activity of strains nor presence or absence of the Hpa I P-fragment were shown to be of importance for severity of vaginitis/vulvitis. Vaginitis/vulvitis was shown to be an all or none response to HSV independent of the rate of replication. The set of virus genes responsible for neuroinvasiveness after vaginal or i.p. inoculation was found to be different. The time course of replication (mainly days 3-6) and inflammation (days 5-10) indicates that inflammation seems to be a secondary immunological phenomenon induced later by the replication phase of HSV. Our system could be useful for separately testing drugs with antiviral and anti inflammatory properties. PMID- 8470959 TI - Isolation and characterization of simian immunodeficiency virus from African white-crowned mangabey monkeys (Cercocebus torquatus lunulatus). AB - Forty-eight of 236 sera from seven species of African non-human primates in Kenya, including those of white-crowned mangabey monkeys (Cercocebus torquatus lunulatus) had antibodies to simian immunodeficiency viruses (SIVs). Isolates of simian lentivirus were obtained from seropositive white-crowned mangabey monkeys which are indigenous in West Africa. This virus, designated as SIVWCM, appeared morphologically similar to HIV by electron microscopy, showed Mg(2+)-dependent reverse transcriptase activity, and induced cytopathic effects in human CD4 positive cells. Western blotting analysis revealed that env products of SIVWCM cross-reacted with those of SIVAGM more strongly than with those of HIV-1 and SIVMAC, and clear hybridization bands were detected with an SIVAGM probe. For comparison of the virus sequence with those of other primate lentiviruses, part of the pol gene and the long terminal repeats (LTRs) were amplified and cloned. Sequencing showed that SIVWCM isolates were closely related to SIVAGM isolates. This study suggested that SIVAGM from the Cercopithecus genus and SIVWCM from the Cercocebus genus may be members of an SIV group that is genetically distinct from the SIV from a sooty mangabey monkey (SIVSMM) of the genus Cercocebus, to which the white-crowned mangabey monkey also belongs. PMID- 8470960 TI - Nucleotide sequence, serology and symptomatology suggest that vanilla necrosis potyvirus is a strain of watermelon mosaic virus II. AB - Vanilla necrosis potyvirus (VNV) is the cause of significant losses to the South Pacific islands vanilla crop. The gene for the coat protein of VNV has been cloned and sequenced. Comparison of this gene with other potyviral coat protein sequences revealed 97% nucleotide sequence homology (98% amino acid homology) to a US isolate of watermelon mosaic virus II (WMV-II), 93% nucleotide sequence homology (96% amino acid homology) to an Australian isolate of WMV-II and 81% nucleotide sequence homology (88% amino acid homology) to soybean mosaic virus-N (SMV-N). Serological analysis, by Western blot and ELISA, confirmed the close relationship between VNV and WMV-II. Furthermore, a limited host range determination found VNV and WMV-II able to infect the same series of test plants. However, symptoms differed significantly on three test species demonstrating that VNV and WMV-II are not identical in biological properties. We suggest that VNV be renamed WMV-II (Tonga). PMID- 8470961 TI - Bleb leak with hypotony after laser suture lysis and trabeculectomy with mitomycin C. PMID- 8470962 TI - Reports by the Silicone Study Group. PMID- 8470963 TI - Reports by the Silicone Study Group. PMID- 8470964 TI - Removing penetrating fishhooks. PMID- 8470965 TI - Effect of continuous circular capsulorhexis and intraocular lens fixation on the blood-aqueous barrier. PMID- 8470966 TI - High-frequency ultrasound digital signal processing for biometry of the cornea in planning phototherapeutic keratectomy. PMID- 8470967 TI - Argon laser closure of conjunctival bleb leak. PMID- 8470968 TI - Management of combined penetrating intraorbital and intracranial trauma. PMID- 8470969 TI - Lisch nodules in Cushing's disease. PMID- 8470970 TI - Bilateral microbial keratitis after radial keratotomy. PMID- 8470971 TI - Clinton's proposal cuts federal payments to physicians. PMID- 8470972 TI - Management of cataract in adults. Quick reference guide for clinicians. The Cataract Management Guideline Panel of the Agency for Health Care Policy and Research. PMID- 8470973 TI - In response to the new guidelines for patients with cataracts. PMID- 8470974 TI - Watson and Crick's legacy and future publications in ophthalmic genetics. PMID- 8470975 TI - Repair and replacement to restore sight. Report from the Panel on Photoreceptor/Retinal Pigment Epithelium. PMID- 8470976 TI - Repair and replacement to restore sight. Report from the Panel on Ganglion Cell/Connectivity. PMID- 8470977 TI - How medicine must change. PMID- 8470978 TI - Anti-inflammatory effect of diclofenac drops after argon laser trabeculoplasty. AB - Using a laser flare-cell meter, the anti-inflammatory effect of diclofenac sodium drops was evaluated after argon laser trabeculoplasty in a double-masked placebo controlled study. Fifty-three eyes with pseudoexfoliative (43 eyes) or pigmentary glaucoma (10 eyes) were randomly assigned to treatment (n = 27) or placebo (n = 26) groups. Diclofenac (0.1%) or placebo drops were administered once before and after trabeculoplasty and then four times daily for a total of 4 days. Visual acuity, intraocular pressure, and anterior chamber flare, measured with the laser flare-cell meter, were evaluated before trabeculoplasty, 3 and 6 hours after trabeculoplasty, and 1, 2, 4, 7, and 14 days after trabeculoplasty. Flare increase after argon laser trabeculoplasty was completely blocked by 0.1% topical diclofenac and the mean of maximal flare increases was reduced significantly in the diclofenac group. Therefore, 0.1% diclofenac drops represent a very efficient anti-inflammatory therapy after argon laser trabeculoplasty. PMID- 8470979 TI - A comparison of two energy levels for noncontact transscleral neodymium-YAG cyclophotocoagulation. AB - In a prospective, clinical trial, 89 patients undergoing transscleral neodymium YAG cyclophotocoagulation for intractable glaucoma were randomized to approximately 4 or 8 J of laser energy per application and followed up for an average of 1 year. The only statistically significant difference between the two groups was early anterior chamber reaction, which was more severe among those receiving 8 J. There was a trend toward better intraocular pressure control in the 8-J group, compared with the 4-J group, with 33 (75%) of 44 patients and 27 (60%) of 45 patients, respectively, requiring no further surgical intervention during the follow-up period. Among those patients not requiring further surgery, there was no significant difference in final visual acuities between the two groups. These findings suggest that within the range of 4 to 8 J, transscleral neodymium-YAG cyclophotocoagulation at the higher energy level may have some advantage with regard to intraocular pressure reduction without an increased risk of visual loss, compared with the same treatment at the lower energy level. PMID- 8470980 TI - One-year results of semiconductor transscleral cyclophotocoagulation in patients with glaucoma. AB - We evaluated 30 consecutive patients with glaucoma treated with semi-conductor diode transscleral cyclophotocoagulation to determine the results and complications of this procedure. Twelve months after surgery the mean (+/- SD) preoperative intraocular pressure of 32.5 +/- 10.9 mm Hg (n = 30) had dropped to 20.8 +/- 15.6 mm Hg (n = 19) (P = .018, paired Student's t test), while the mean number of preoperative medications received decreased from 2.0 to 1.8 (P = .060, Wilcoxon's Signed Rank Test). One year after surgery three patients (10%) were unavailable for follow-up, eight (27%) had required other surgical procedures to control the intraocular pressure, 17 (56%) had controllable intraocular pressure of 21 mm Hg or below or received pain relief from the diode laser alone, and two (7%) patients with controlled intraocular pressure had suffered visual loss. Other complications included mild conjunctival hyperemia and uveitis in all patients and mild ocular pain in six patients. This study suggests the usefulness of diode transscleral cyclophotocoagulation in reducing the intraocular pressure for up to 1 year. PMID- 8470981 TI - Ocular penetration of ceftriaxone, ceftazidime, and vancomycin after subconjunctival injection in humans. AB - Vancomycin (25 mg), ceftriaxone (125 mg), and ceftazidime (100 mg) were given by subconjunctival injection before vitrectomy to patients with uninfected eyes. Most of the patients had diabetic vitreous hemorrhage with or without traction retinal detachments, and some had rhegmatogenous retinal detachments with proliferative vitreoretinopathy. Samples of vitreous were obtained by pars plana vitrectomy at intervals from 46 minutes to 4 hours 13 minutes after the subconjunctival injection. The median vitreous concentrations of all three drugs were below the limit of detection. Vitreous concentrations of these drugs after a single subconjunctival injection are exceedingly low. PMID- 8470982 TI - Leber's hereditary optic neuropathy. Clinical manifestations of the 14484 mutation. AB - OBJECTIVE: To define the clinical features of Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation and to compare these features with those associated with three other pathogenetic mutations. DESIGN AND PATIENTS: Clinical and historical data were collected from 19 visually symptomatic patients from 17 independent pedigrees with the molecularly confirmed 14484 mutation. MAIN OUTCOME MEASURES: Demographic features, age of onset of visual loss, nadir of visual acuity, occurrence and timing of visual recovery, family history of visual loss, and associated medical and environmental conditions. RESULTS: Clinical characteristics associated with the 14484 mutation are similar overall to those of the three other primary mutations. One notable distinguishing feature is the higher incidence of visual recovery among patients with the 14484 mutation. Thirty-seven percent of our patients experienced visual recovery compared with 5% with the 11778 mutation (P < .001), 22% with the 3460 mutation, and 29% with the 15257 mutation. The average age of onset of visual symptoms for the patients with the 14484 mutation who had visual recovery was younger than for those without recovery (19.6 vs 30.6 years). Thirteen of the 19 patients had a history of metabolic disturbance, trauma, or substance abuse. CONCLUSIONS: Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation may have a better prognosis for visual recovery. The phenotypic expression of the 14484 mutation may be influenced by concurrent medical and environmental factors. Molecular genetic testing in suspected Leber's hereditary optic neuropathy is useful to confirm the diagnosis and to assess visual prognosis. PMID- 8470983 TI - Anterior corneal disease of epidermolysis bullosa simplex. AB - We report the histopathological findings of the anterior cornea from a patient with skin biopsy-proven epidermolysis bullosa simplex. As seen with light microscopy, the cornea had a fibrocellular pannus deep to a thickened epithelial basement membrane. Transmission electron microscopy of the anterior cornea demonstrated a nonhomogeneous basal epithelial layer with abnormal attachment complexes to an irregular, multilaminar basement membrane. The findings of transmission electron microscopy of the bulbar conjunctiva were normal. PMID- 8470984 TI - A prospective study of aspirin use and cataract extraction in women. AB - We examined the association between aspirin use and the rates of cataract extraction during 8 years of follow-up in a large prospective study of women, the Nurses' Health Study. From 1980 to 1988, we documented 448 senile cataracts diagnosed and extracted during 434,680 person-years of follow-up. While we observed a modest positive association at the higher doses of aspirin use in the age-adjusted analyses, no association was found after accounting for other cataract risk factors (relative risk for > or = 20 years of use, 1.08; 95% confidence interval, 0.84 to 1.39). Among women who consumed seven or more tablets per week for 20 or more years, there was no suggestion of protection; if anything, a nonsignificantly elevated risk was observed (relative risk, 1.31; 95% confidence interval, 0.94 to 1.80). We observed no consistent difference in the relationship between aspirin use and cataract when assessed by age. Overall, we found no evidence to support the substantial reduction in risk of cataract among aspirin users as reported in several previous studies. PMID- 8470985 TI - National outcomes of penetrating keratoplasty. Risks of endophthalmitis and retinal detachment. AB - We studied rehospitalization for endophthalmitis or retinal detachment (RD) in 40,351 Medicare beneficiaries who were admitted to US hospitals for penetrating keratoplasty (PK) between 1984 and 1987. This cohort represents 56.5% of all PKs performed during this period for recipients of age to receive Medicare benefits. Penetrating keratoplasty was combined with intracapsular cataract extraction in 1188 patients (2.9%) and with extracapsular cataract extraction in 7038 patients (17.4%). Anterior vitrectomy was performed in 8428 patients (20.9%). The risk of rehospitalization for endophthalmitis within 6 months of PK was 0.77%. Concurrent anterior vitrectomy increased this risk to 1.03% (P = .004). The risk of rehospitalization for RD within 2 years of PK was 1.85%. Concurrent anterior vitrectomy increased this risk to 2.49% (P = .0001). Combined PK and intracapsular cataract extraction demonstrated a 3.9-fold increased rate of RD compared with PK and extracapsular cataract extraction (P = .0001). Anterior vitrectomy with PK and extracapsular cataract extraction increased the risk of RD 4.3-fold compared with PK and extracapsular cataract extraction alone (P = .007). Men were at a 68% higher risk of RD than women (P = .0001). The risk of rehospitalization for endophthalmitis following PK is five times higher and the risk of RD two times higher than that reported following cataract surgery. Anterior vitrectomy, however, results in similar risk increases following either surgery. PMID- 8470986 TI - Sunlight and age-related macular degeneration. The Beaver Dam Eye Study. AB - OBJECTIVE: To investigate the relationship of sunlight exposure with age-related maculopathy. This was investigated in the population-based Beaver Dam Eye Study. DESIGN: In this cross-sectional population-based study, questionnaire data about sunlight exposure were obtained. Stereoscopic color fundus photographs were graded to determine the presence of age-related maculopathy. PARTICIPANTS: People aged 43 through 84 years who resided in Beaver Dam, Wis, between 1987 and 1988 were examined between 1988 and 1990. RESULTS: Light exposure was not associated with early age-related maculopathy in women. In men, after adjusting for age, the amount of time spent outdoors in summer was associated with increased retinal pigment (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01 to 2.04). Wearing eyeglasses was inversely associated with increased retinal pigment (OR, 0.75; 95% CI, 0.58 to 0.97), and the use of hats and sunglasses was inversely associated with soft indistinct drusen (OR, 0.61; 95% CI, 0.38 to 0.98). The amount of leisure time spent outdoors in summer was significantly associated with exudative macular degeneration (OR, 2.26; 95% CI, 1.06 to 4.81) and late maculopathy (OR, 2.19; 95% CI, 1.12 to 4.25). There were no associations between estimated ambient UV-B exposure and age-related maculopathy. CONCLUSIONS: These data suggest that exposure to sunlight may be associated with age-related maculopathy. However, longitudinal studies of these associations are needed. PMID- 8470987 TI - Infectious crystalline keratopathy. The role of bacterial exopolysaccharide. AB - OBJECTIVES: Infectious crystalline keratopathy is a unique pauci-inflammatory infection of the cornea most commonly due to viridans type streptococci. We investigated the hypothesis that production of exopolysaccharide by streptococci, a property that can be induced by growth conditions, may contribute to the pathogenesis of infectious crystalline keratopathy by suppressing the ocular immune response. METHODS: Streptococcus sanguis type II was grown under two conditions, conventionally in brain-heart infusion broth and in 5% sucrose supplemented brain-heart infusion broth, to promote exopolysaccharide formation. Rabbit corneas were inoculated by passage of 9-0 silk sutures soaked in bacterial suspensions. RESULTS: Arborizing, sharply demarcated pauci-inflammatory lesions were noted in 71% of rabbit corneas inoculated with S sanguis type II grown in sucrose-supplemented media and in 25% of control corneas (P = .05). Suppurative lesions developed in the remaining corneas. Histologic evaluation of infectious crystalline keratopathy lesions revealed characteristic features. CONCLUSION: Increased exopolysaccharide formation by S sanguis type II is associated with production of infectious corneal lesions that resemble those of infectious crystalline keratopathy. PMID- 8470988 TI - Reflectance feedback control of photocoagulation in vivo. AB - OBJECTIVE: The objective of this research was to build a real-time feedback system that controlled lesion size. Two-dimensional reflectance images were acquired with a charge-coupled device camera during irradiation, and argon laser exposure was ended when parameters of the image reached prespecified values. METHODS: The real-time feedback control system was tested by creating lesions at different power levels in pigmented rabbits. Laser exposure time was controlled by monitoring the central reflectance. RESULTS: Results of feedback-controlled lesions formed in vivo in pigmented rabbits are presented. An ability to produce uniform lesions despite variation in tissue absorption or changes in laser power is demonstrated. CONCLUSIONS: Reflectance control of photocoagulation is possible; incorporation of feedback during photocoagulation has numerous therapeutic and safety benefits over current ballistic delivery. PMID- 8470989 TI - Effect of oxymetazoline on aqueous humor dynamics and ocular blood flow in monkeys and rabbits. AB - OBJECTIVE: To evaluate the ocular effects of oxymetazoline hydrochloride, an alpha 2 agonist, in cynomolgus monkeys and albino rabbits. METHODS: Intraocular pressure was measured before and for 6 hours after application to glaucomatous monkey eyes. Outflow facility and aqueous flow rates were measured in normal monkey eyes. Uveoscleral outflow was measured in rabbit eyes. Ocular peak pulse volume was determined with the ocular blood flow system in normal and glaucomatous monkey eyes. RESULTS: Single applications of ozymetazoline reduced (P < .001) intraocular pressure up to 6.0 +/- 1.0 mm Hg (mean +/- SEM). Enhancement of the ocular hypotensive effect was observed with 5-day twice-daily administration. Outflow facility was unaltered; aqueous flow rate was decreased (P < .001) by 39% in the treated eyes compared with baseline values; and uveoscleral outflow was increased (P < .005) by 56% in the treated eye. Peak pulse volume was unchanged. CONCLUSION: Oxymetazoline reduces intraocular pressure by decreasing aqueous humor flow rates and increasing uveoscleral outflow. Oxymetazoline may have clinical potential as an ocular hypotensive drug. PMID- 8470990 TI - The history of vitamin A and its ophthalmic implications. A personal viewpoint. PMID- 8470991 TI - Response of retinal capillary hemangioma to cryotherapy. PMID- 8470992 TI - Peripapillary subretinal neovascularization associated with coloboma of the optic nerve. PMID- 8470993 TI - Possible health effects of 50/60Hz electric and magnetic fields: review of proposed mechanisms. AB - There is inconclusive evidence from both epidemiological and laboratory studies that fields similar to those produced by electrical power transmission lines may contribute to certain diseases including cancer. There are several objections to a hypothesis of a direct causative link, based on identifying a mechanism of interaction. One is that the energy density of the fields is several orders of magnitude smaller than that associated with random thermal motion in biological tissue. Secondly, the induced currents are many times smaller than endogenous currents associated with normal membrane processes. A comparison of current densities and characteristics associated with field-related phenomena such as electrosensitivity in species of fish, night-time melatonin depression in rodents, limb regeneration in amphibians and magnetophosphenes in humans reveals little that can be of use in determining a 'response metric', yet guide-lines for the general public are in fact based on this quantity, for immediate effects at least. Indeed, currents induced by the electric component of environmental 50 Hz fields are of similar magnitude to those induced by the magnetic component, yet epidemiological studies have identified surrogates of the latter as the significant exposure metric in relation to cancer incidence. Proposed mechanisms, many of which are still at the 'working hypothesis' stage, are compared with experimental evidence. Some conflict with epidemiological evidence, itself not strong, but becoming stronger, is apparent. PMID- 8470994 TI - Testing random number generators for Monte Carlo applications. AB - Central to any system for modelling radiation transport phenomena using Monte Carlo techniques is the method by which pseudo random numbers are generated. This method is commonly referred to as the Random Number Generator (RNG). It is usually a computer implemented mathematical algorithm which produces a series of numbers uniformly distributed on the interval [0,1). If this series satisfies certain statistical tests for randomness, then for practical purposes the pseudo random numbers in the series can be considered to be random. Tests of this nature are important not only for new RNGs but also to test the implementation of known RNG algorithms in different computer environments. Six RNGs have been tested using six statistical tests and one visual test. The statistical tests are the moments, frequency (digit and number), serial, gap, and poker tests. The visual test is a simple two dimensional ordered pair display. In addition the RNGs have been tested in a specific Monte Carlo application. This type of test is often overlooked, however it is important that in addition to satisfactory performance in statistical tests, the RNG be able to perform effectively in the applications of interest. The RNGs tested here are based on a variety of algorithms, including multiplicative and linear congruential, lagged Fibonacci, and combination arithmetic and lagged Fibonacci. The effect of the Bays-Durham shuffling algorithm on the output of a known "bad" RNG has also been investigated. PMID- 8470995 TI - Scatter radiation in mammography. AB - Current information pertinent to scatter radiation for mammographic x-ray spectra is limited. Data presented by the National Council on Radiation Protection and Measurements (NCRP), the current shielding authority, are restricted to 50 kVp tungsten target spectra and contain several incompatibilities with the modern mammographic situation. The ratio of scattered to incident exposure was measured for two molybdenum target spectra (36 kVp, 30 microns molybdenum filtration and 49 kVp, 50 microns aluminium filtration). The maximum scatter ratio occurred at 150 degrees to the primary beam direction for both spectra; the values were (1.73 +/- 0.09) x 10(3) and (2.6 +/- 0.1) x 10(3) respectively for a field area of 400 cm2, a scattering distance of 1 m and a primary beam exposure distance of 1 m from the x-ray source. The results obtained differ significantly from NCRP based data presently used for mammographic shielding calculations. The consequences of these differences are discussed. PMID- 8470996 TI - Development of the national radionuclide dose calibrator standardisation service. AB - The Australian Nuclear Science and Technology Organisation, acting as agent for the CSIRO Division of Applied Physics, maintains the Australian standard of measurement for activity. The standard includes all nuclear medicine gamma emitters and a new standard for pure positron emitters. Under Section 10 of the National Measurement Act 1960, if a measurement is made for a legal purpose, or if the legality of a measurement is in dispute, it can only be confirmed if the following two conditions are fulfilled: (a) that the measurement be in terms of the prescribed Australian legal units of measurement. (b) that it can be proven to be traceable to an Australian primary standard of measurement. To satisfy these requirements, radionuclide dose calibrators require a calibration report determined by Ansto. For this reason, Ansto has developed the national radionuclide dose calibrator standardisation service. PMID- 8470997 TI - International Atomic Energy Agency/World Health Organisation TLD radiotherapy dosimetry intercomparison. PMID- 8470998 TI - Data acquisition for linac based stereotactic radiosurgery. AB - In September 1991 a Philips Stereotactic Radiosurgery System (SRS 200) was installed in the Radiotherapy Department at Sir Charles Gairdner Hospital for use with an existing 6MV linear accelerator. The treatment planning software requires tables of Output Factors, Tissue Maximum Ratios (TMRs) and Off-Axis Ratios (OARs) for each specific linac/collimator set combination. Conventional techniques of acquiring radiation dose data for patient treatment planning were not suitable for the very small field sizes (5-30mm diameter) to be measured. Output Factors relative to a 100 x 100 mm field were measured using a large water tank and solid state diode detectors. The SRS 200 base frame which usually supports the special collimators could not be used with the tank in place and so a method for aligning the central axis of the beam, the SRS 200 collimators and diode was developed to improve the accuracy of measurement. TMRs were measured using two independent methods, similarly for the OARs. The first method of measuring TMRs made use of the large water tank and diode detectors. The second method employed the use of solid water phantom slabs seated on the base frame of the SRS 200. OARs were first measured with the solid water phantom slabs and diode; the second method made use of the technique of film dosimetry. Finally, a spherical water phantom was designed and built to check the total system accuracy. Agreement between sets of results measured by the independent methods was within 0.3% on average for TMRs and 0.25mm at the 50% dose level in most cases for the OARs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8470999 TI - A device for measuring compression force in mammography. AB - Compression in mammography is an accepted technique for improving image quality and reducing dose, but excessive compression can cause pain and other undesirable effects. Therefore, maximum compression force should be measured in a quality assurance programme. A compression force meter, based on a load cell design, has been constructed and used to make compression force measurements on three GE Senographe 600T mammography machines. These measurements show that the conversion from pneumatic pressure (as indicated on the machine) to applied compression force is given by Compression Force (N) = (79.0 +/- 0.9) x Pneumatic Pressure (bars) + (12.2 +/- 4.0). Using this equation and pneumatic pressure settings on nine GE Senographe 600T units in our quality assurance programme, the maximum compression force in clinical use ranges from 102 to 150 N with a mean of 126 N. This is lower than guidelines used in the United States and the United Kingdom. PMID- 8471000 TI - Myogenic and flow-dependent control mechanisms in the coronary microcirculation. AB - We have recently gained evidence that segmental coronary microvascular diameters, and therefore resistances, are controlled by myogenic and endothelial responses to pressure and flow. Furthermore, intact heart studies are demonstrating that these mechanisms may interact importantly with the metabolic mechanisms primarily governing coronary blood flow. Further studies utilizing measurement of segmental coronary microvascular diameters in isolated microvessels and in the beating heart may elucidate the nature of these interactions. Clinical studies may determine whether reversal of endothelial impairment in the diseased coronary microcirculation contributes to autoregulatory vasodilation, increases resting myocardial perfusion, and increases the threshold for myocardial ischemia during exercise. PMID- 8471002 TI - In vivo assessment of the inotropic and toxic effects of oxidized ouabain. AB - Oxidized ouabain, a product of the oxidative cleavage of the rhamnose ring in ouabain has been found to have a higher inotropic toxic ratio in cultured cardiac myocytes. The purpose of our study was to evaluate the efficacy and toxicity of oxidized ouabain in comparison with ouabain in intact animals. Drugs were infused to healthy cats; the positive inotropic effect, and the time-course of development of arrhythmia were followed and recorded until death. Oxidized ouabain was associated with a higher increase in arterial blood pressure, a mean increase of 41 +/- 19% as compared with 21 +/- 8% in the ouabain group (p < 0.10). There were no significant differences in maximal increases of dP/dt or dP/dt/P (65 +/- 29%, 28 +/- 10% for oxidized ouabain and 49 +/- 16%, 27 +/- 11% for ouabain, respectively). The mean doses causing persistent arrhythmia (toxic dose) were 93 +/- 23 micrograms/kg of oxidized ouabain vs 39 +/- 14 micrograms/kg of ouabain. Lethal arrhythmias were produced by 215 +/- 46 micrograms/kg of oxidized ouabain and 62 +/- 16 micrograms/kg of ouabain. The ratio of toxic to lethal doses was 0.62 +/- 0.11 for ouabain vs 0.45 +/- 0.09 for oxidized ouabain (p < 0.05), but the inotropic to toxic dose ratios were not different. We conclude that oxidized ouabain acts similarly to the known cardiac glycosides in doses which produce inotropic effects in cats, has a lower potency as compared to ouabain, and appears to have a more benign course of intoxication. PMID- 8471001 TI - Effects of adenosine on electrical activity of isolated guinea pig hearts. AB - Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated. Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine in concentrations of 3 and 10 microM reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636 +/- 109 and 111 +/- 35 (mean +/- SE) beats, respectively. During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 microM, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed. These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias. PMID- 8471003 TI - Catecholamine-induced cardiac necroses: protective effect of leucocytopenia, influence of an S2 antagonist, thromboxanesynthetase inhibitor and prostacycline analogue. AB - The influence of various drugs and leucocytopenia (induced by cyclosphamid) on isoproterenol(40 mg/kg, s.c.)-induced cardiac necroses was investigated in female SPF Sprague Dawley rats. The influence of fibrinogen reduction was investigated in spontaneously hypertensive rats (SHR). 8-15% of the area of 15 cross-sections were evaluated with a computer-aided morphometric device allowing classification of number and area of necroses. The reduction of number and area of necroses amounted to approximately: 50% by prostacyclin analogue, 25% by S2 inhibition (ketanserin). Inhibition of thromboxane synthesis and fibrinogen reduction from elevated values (200 mg/dl) below the limit of detection by infusion of 35 U/kg Ancrod in SHR had no significant effects, where in SHR only 10 mg/kg isoproterenol were tolerated with a higher extent of necrosis formation. Leucocytopenia caused a reduction of necroses of over 90%. The condition of mismatch of oxygen consumption and supply induced by high doses of isoproterenol can be considered a model of angina pectoris. The effect of leucocytopenia indicates an essential role of leucocytes in necrosis formation in both situations. PMID- 8471004 TI - The hemodynamic effect of dietary calcium supplementation on rat renovascular hypertension. AB - Mechanisms which could be responsible for the hypotensive effects of increasing calcium intake from 1.2 to 2.5% of diet were examined in two kidney, one clip renovascular hypertension (2K, 1C RHV) in male Sprague-Dawley rats. Plasma renin activity was elevated similarly in NCA and HCA rats. No evidence for volume or phosphate depletion was found in HCA animals. Cardiac output was not different. Decreased sensitivity was demonstrated to moderate doses of norepinephrine in HCA rats, while vascular reactivity to exogenously administered angiotensin II over the range of doses used was not different between diets. The antihypertensive effect of supplemental calcium was associated with a 39% reduction in systemic vascular resistance. Therefore, dietary calcium supplementation lowers blood pressure in 2-K, 1C RVH primarily due to a systemic vasodilatation and reduced vascular reactivity to moderate doses of norepinephrine. PMID- 8471006 TI - Calculated mean arterial blood pressure in critically ill neonates. AB - Mean arterial pressure (MAP) is the area under the pressure wave form averaged over the cardiac cycle. A widely used rule of thumb to estimate MAP of peripheral arterial pressure waves in adults is adding one-third of the pulse pressure (PP) to diastolic arterial pressure (DAP). However, radial artery pressure waves in newborns differ from those in adults and resemble proximal aortic pressure waves, so that the above-mentioned calculation of MAP may not be correct. The present study was set up to obtain an arithmetical approximation to derive MAP from blood pressure waves measured in the radial artery of the neonate. We accurately recorded about 300 invasively obtained blood pressure curves in the radial artery of 10 neonates admitted for intensive care. We found that MAP in the radial artery in these neonates can be well approximated by adding 46.6% PP to DAP (range 43.0-50.1%). We suggest that the rule of thumb to derive MAP from radial artery waves in the neonate to be approximately the average of systolic and diastolic pressure, as opposed to adding one-third of the pulse pressure to the diastolic value in the adult. PMID- 8471005 TI - Myocardial contractility and ventricular myosin isoenzymes as influenced by cardiac hypertrophy and its regression. AB - Changes in myocardial contractility and ventricular myosin isoenzymes were examined during pressure-overloaded cardiac hypertrophy in rats. Effects of regression of cardiac hypertrophy were also examined. Cardiac hypertrophy was induced by abdominal aortic constriction in 7-week-old male Wistar rats. Regression of cardiac hypertrophy was obtained by opening the aortic band. Myocardial contractility was estimated by measuring isometrically developed tension and maximum rate of tension rise (+dT/dtmax) in isolated left-ventricular papillary muscles perfused with Tyrode solution (32 degrees C, pH 7.4, bubbled with 95% O2.5% CO2, stimulation frequency: 0.2 Hz). Left-ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis and the isoenzyme pattern was determined by densitometry. Isometrically developed tension (T) in hypertrophic myocardium remained unchanged, but +/-dT/dtmax decreased as compared with hearts of normal rats. Decreased +/-dT/dtmax recovered near to the level in normal rats by regression of cardiac hypertrophy. Left-ventricular myosin isoenzyme pattern shifted towards VM-3 in hypertrophied myocardium and shifted again toward VM-1 by regression of cardiac hypertrophy. In conclusion, myocardial contractility and ventricular myosin isoenzymes were changed in pressure overloaded hypertrophy in rats and these changes were reversible to a normal level by regression of cardiac hypertrophy. PMID- 8471007 TI - Geometric and muscle physiological factors of the Frank-Starling mechanisms. AB - The relation between left-ventricular stroke volume (SV) and end-diastolic volume (EDV) was determined based on angiocardiographic measurements in 10 open-chest minipigs under varying filling conditions (blood letting or infusions). The results were compared with a theoretical relation calculated under the assumption of varying EDV but constancy of myocardial properties. In contrast to the linear increase of SV as a function of EDV as found in the animal experiments, the calculated curve reveals a maximum near the normal operating point with a decrease in the range of higher EDV. It can be concluded that the well-known increase of SV with increasing ventricular filling, beyond the normal EDV, is almost completely due to muscle physiological factors (mainly increase in Ca2+ sensitivity of the contractile apparatus), whereas the decrease of SV in the range of low filling pressure is mainly due to the geometrical conditions. PMID- 8471008 TI - Relations between social skills and high-risk sexual interactions among adolescents. Current issues and future directions. AB - Researchers have begun to employ social-skills training in efforts to change the sexual behavior of adolescents. However, despite the promise of social-skills training, little is known about how social skills are related to the sexual practices of adolescents. The present article reviews the current literature and proposes a conceptual framework for understanding the relations between social skills and sexual behavior of adolescents by (a) examining the relationship between sexual activity and social skills, (b) examining the development of sexual-interaction skills and deficits, (c) summarizing what is currently known about the relations between social skills and sexual behavior, (d) discussing current issues in the assessment and treatment of sexual-interaction skills deficits, and (e) proposing some directions for needed research that will add both to our current knowledge base and to the effectiveness of applied intervention efforts. PMID- 8471009 TI - "We'll cross that hurdle when we get to it". Teaching athletic performance within adaptive physical education. AB - Persons with developmental and physical disabilities who are enrolled in educational programs often participate in adaptive physical education classes. Primarily, these classes are designed to provide individuals with the opportunity to develop their physical abilities. However, they can also serve as a training ground for the Special Olympics. Teaching the motor skills that are prerequisite to participation in many adaptive physical education and Special Olympics activities can be a formidable objective. This study demonstrates how a person with developmental disabilities was taught, by way of stimulus control shaping, the necessary motor skills to enable him to participate in the hurdling event at the Special Olympics. PMID- 8471010 TI - Behavioral interventions to reduce maladaptive responding in youth with dual sensory impairment. An analysis of direct and concurrent effects. AB - Many persons who have multiple sensory, physical, and developmental disabilities display behaviors that interfere significantly with adaptive functioning and social acceptance. In this investigation, the efficacy of multiple component behavioral interventions for reducing maladaptive responding exhibited by two individuals with dual sensory impairment and profound mental retardation was evaluated. Results indicated that differential reinforcement of other behavior (DRO) approaches were not effective in either case. However, when deceleration procedures (overcorrection or brief physical restraint) were added, target behaviors decreased quickly. Also, interventions were faded in such a way that gains were maintained for 6 months with only minimal effort by staff. Ongoing assessment of concurrent effects of behavior reduction strategies revealed increases in time on task or amount of work completed, even though these responses were not targeted specifically. Yet negative side effects (e.g., increases in self-stimulation) also were documented, highlighting the importance of evaluating multiple behaviors during intervention. Finally, despite the fact that objective assessments led to positive conclusions regarding treatment efficacy, ratings of baseline and treatment behavior samples by independent judges showed overall improvement in only one case. These findings suggest the need for multifaceted evaluation to determine the utility of interventions in applied settings. PMID- 8471011 TI - Using independence training to teach independent living skills to children and young men with visual impairments. AB - Two groups of students with visual impairments were taught various independent living skills. Of the 7 students, 5 also had a diagnosis of mental retardation. One group (3 first graders) was taught the tasks of folding a shirt, making an emergency telephone call, and spreading soft foods with a knife. The other group (4 young men) was taught to increase leisure skills through three different leather-work tasks. Independence training was conducted in a group format and included social learning components (e.g., self-evaluation, peer evaluation and reinforcement) in addition to traditional operant procedures (e.g., modeling, prompting). However, because of the presence of visual impairments, a physical and verbal modification of modeling was used, whereby the subject was physically guided through the steps and simultaneously provided with a narration of the steps. A multiple baseline design across behaviors demonstrated the efficacy of the comprehensive training package in training various independent living skills to the two groups of visually impaired and mentally retarded students. Social validity measures demonstrated the clinical significance of the subsequent changes in behavioral skills. Follow-up data collected 10 months after the completion of training indicated a good degree of maintenance. The current positive results show that training procedures used exclusively with persons with mental retardation can be modified and be effective with a different and younger population, while targeting different independent living skills. PMID- 8471012 TI - Behavioral assessment of anxiety in older adults. Some comments. AB - The behavioral assessment of anxiety in older adults is reviewed in this article. Despite the high rate of anxiety symptoms uncovered during the course of large scale epidemiological studies, the comprehensive evaluation of anxiety in this age group (55 and over) is not highly sophisticated at this juncture. In this review, diagnostic issues, psychometric evaluation, motoric assessment, and psychophysiological assessment are considered. Throughout the articles, gaps in the extant research are identified, and a research agenda for the future is developed. PMID- 8471013 TI - [The hematologic parameters, concentrations of minerals and metabolic products and activities of enzymes in sheep]. AB - In the period of March 1988-March 1989, in 20 Lower Austrian sheep breeding farms blood samples were taken in two-month intervals from sheep of the following breeds: 130 Tyrolean Mountain sheep, 59 German Improved Land breed, 59 East Friesian and 57 German Blackheaded Mutton breed sheep. The following standards for sheep were evaluated: Erythrocytes 7,2-11,9 T/L, haematocrit 0,25-0,41 1/L, haemoglobin 82-147 g/L, lymphocytes 34-80%, segmented neutrophils 10-53%, band neutrophils 1-3%, eosinophilic granulocytes 0-24%, basophilic granulocytes 0-1%, monocytes 0-1%, calcium 1,8-2,8 mmol/L, phosphorus 1,0-2,6 mmol/L, magnesium 0,6 1,3 mmol/L, total protein 53-81 g/L, albumin 22-41 g/L, aspartate aminotransferase 27-81 U/L, alanine aminotransferase 3-25 U/L, gamma glutamic transaminase 24-59 U/L, alkaline phosphatase 44-355 U/L, creatine kinase 3-130 U/L, glutamic dehydrogenase 2,0-36,5 U/L, total bilirubin 0,7-5,1 mumol/L, cholesterol 1,1-3,2 mmol/l, urea nitrogen 1,3-12,7 mmol/l, creatinine 50-112 mumol/L. Apart from that, additional standards for the mentioned breeds of sheep were evaluated, revealing significant differences. Also the age and the time of the year proved to have an influence upon the ascertained blood values. PMID- 8471014 TI - [Sarcosporidia as the cause of sudden death during anesthesia in sheep]. AB - The first two out of an experimental group of 17 sheep assigned for orthopaedic surgery died during inhalation anaesthesia with halothane-nitrous oxide-oxygen before the arthrotomy of the knee joint could start. Further casualties could be prevented by the use of epidural anaesthesia. Each of the 17 sheep underwent a pathologic-anatomical, histological, bacteriological and parasitological examination. It was found that all of them were infected with sarcosporidia oocysts with myocarditis of different intensity. Possible infections with sarcosporidia-oocysts in animals, which could have had contact to carnivora, and which are taken for therapeutic surgery or for an experiment should be taken into consideration, because the lesion in the heart due to sarcosporidia-oocysts can be the cause of sudden death. PMID- 8471015 TI - [The effect of toxins from Pasteurella multocida type D in calves in vivo]. AB - By intratracheal injection of purified dermonecrotic toxin from a Pasteurella multocida type D strain, pneumonitis in calves could be produced. This demonstrates the important role of this toxin in the pathogenesis of pneumonitis in calves. PMID- 8471016 TI - [Yersinia pseudotuberculosis as a possible cause of abortion in sheep (short communication)]. AB - A case report is given on cases of abortion in a flock of sheep herded on different pastures. In three fetuses Yersinia pseudotuberculosis could be detected additionally to Chlamydia for the first time in the district of the veterinary office of Cottbus. PMID- 8471017 TI - [Experimental studies on the development of an antigen-capture test (Capture ELIFA) for the detection of Coxiella burnetii in cow's milk as a possible alternative to animal studies]. AB - A sensitive and specific Capture-ELIFA (Enzyme-linked-Immunofluorescent Assay) for the detection of Coxiella burnetii was developed using a monoclonal antibody and a rabbit immune serum, both directed against Coxiella burnetii, strain Nine Mile, phase I. A combination of centrifugation, Pronase-K-digestion and heat treatment proved to be advantageous for concentrating, exposure and inactivating of Coxiella antigens in milk samples. Using this method of sample preparation 4 x 10(3) coxiella particles/ml could be detected in experimentally contaminated milk samples by the optimized Capture-ELIFA. Preliminary results of comparative investigations indicate that the Capture-ELIFA is more sensitive than the inoculation of guinea pigs and subsequent detection of seroconversion. PMID- 8471018 TI - [Measurement of the mucociliary transport velocity in the trachea of calves]. AB - A measuring method is presented for the determination of the velocity of intratracheal mucociliary transport in calves, which is applicable for nonanaesthetized animals directly in the calf stable. The transport velocity in the trachea of clinically healthy calves was found to be about 15 mm/min, which is in agreement with other reports. PMID- 8471019 TI - [Legal problems--particularly regarding doping--in animal purchasing]. AB - The role of the veterinarian in giving health certificates for animals for different purposes in the trade of livestock or sports are being discussed from the legal point of view. A set for falsification secure transportation of blood samples for doping tests is being demonstrated. PMID- 8471020 TI - Polymorphism of two closely linked hexokinase loci in the grasshopper Oxya japonica japonica (Orthoptera: Acrididae: Oxyinae). PMID- 8471021 TI - Caprine blood groups. 2. The C, G, H, I, J, K, L, N, and Q systems. AB - Nine blood group systems of goats were identified using 12 caprine reagents produced by absorption of alloimmune antisera. The caprine C blood group system, possibly homologous to the ovine C blood group system, was characterized by two reagents and shown to be controlled by three alleles, C12, C25, and C-. A more complex blood group system of goats, designated G, was identified using three reagents and shown to be controlled by six codominant alleles (G10.19.20, G10.19, G10.20, G10, G19, G20) and a recessive allele (G-). A further seven one-factor two-allelic systems were identified by seven reagents. The nine genetic systems provided exclusion probabilities of 0.479, 0.492, 0.548, and 0.572 in Australian Angora, Dairy, Cashmere, and Texan Angora goat breeds, respectively. PMID- 8471022 TI - Chromosomal effects on peptidase activities in Drosophila melanogaster. AB - The peptidase system in Drosophila melanogaster (dipeptidase-A, -B, and -C and leucine aminopeptidases G and P) was used as a model to study the effects of modifier genes on activity of enzymes with similar functions. A screen of X, second, and third chromosome substitution isogenic lines revealed the presence of activity modifiers for peptidases on all three chromosomes. Correlation analyses indicated that covariation between some of the peptidase activities is independent of genetic background, while others are associated with variable second chromosomes. Chromosome-specific effects on Km, Vmax, and specific activity of partially purified peptidases were also detected. Moreover, a repeatable technique using anion-exchange column chromatography allowed the characterization of possibly two putative peptidic enzymes, glycyl-L-isoleucine ase and L-leucyl-L-proline-ase, whose kinetic properties differ from the dipeptidases and the leucine aminopeptidases. These findings confirm the existence of activity modifiers for peptidases, much like other enzymes in Drosophila melanogaster. PMID- 8471023 TI - A correction for allele frequency estimates derived from isofemale lines. AB - Isofemale lines are commonly used in Drosophila and other genera for the purpose of assaying genetic variation. Isofemale lines can be kept in the laboratory for many generations before genetic work is carried out, and permit the confirmation of newly discovered alleles. A problem not realized by many workers is that the commonly used estimate of allele frequency from these lines is biased. This estimation bias occurs at all times after the first laboratory generation, regardless of whether single individuals or pooled samples are used in each well of an electrophoretic gel. This bias can potentially affect the estimation of population genetic parameters, and in the case of rare allele analysis it can cause gross overestimates of gene flow. This paper provides a correction for allele frequency estimates derived from isofemale lines for any time after the lines are established in the laboratory. When pooled samples are used, this estimator performs better than the standard estimator at all times after the first generation. The estimator is also insensitive to multiple inseminations. After the lines have drifted one Ne generations, multiple inseminations actually make the new estimator perform better than it does in singly inseminated females. Simulations show that estimates made using either estimator after the lines have drifted to fixation have a much greater error associated with their use than do those estimates made earlier in time using the correction. In general it is better to use corrected estimates of gene frequency soon after lines are established than to use uncorrected estimates made after the first laboratory generation. PMID- 8471024 TI - Caprine blood groups. 1. The B system. AB - Twelve of 24 monospecific caprine reagents produced by absorption of alloimmune antisera identified a complex blood group system of goats which was designated B, based on the results of a small comparison test with ovine reagents. The frequencies of the 12 B factors differed significantly among the Australian Angora, Texan Angora, Cashmere, and Dairy goat breeds. Three of the antigens detected by the reagents were shown to be related as linear subtypes, designated Ba1, Ba2, and Ba3, and inherited as alleles. The segregations of B factors in 80 sire groups involving 1086 offspring demonstrated that groups of B factors (phenogroups) segregated as products of allelic genes. PMID- 8471025 TI - Identification of three Wx proteins in wheat (Triticum aestivum L.). AB - Nullisomic analysis of waxy (Wx) protein of hexaploid wheat (Triticum aestivum L.) cv. "Chinese Spring" using two-dimensional polyacrylamide gel electrophoresis revealed that three Wx loci, Wx-A1, Wx-B1, and Wx-D1, located on chromosome arms 7AS, 4AL, and 7DS, produce three distinct Wx subunit groups, subunit group-A (SGA), SGB, and SGD, respectively. SGA has a higher molecular weight and a more basic isoelectric point (pI) than the other two. SGB and SGD have the same molecular weight but a slightly different pI range. Owing to the detection of these three subunit groups, we were able to identify the expression of three waxy genes in wheat endosperm and to find two types of mutants among Japanese wheat cultivars, one lacking SGA and the others SGB. These results suggest the possibility of breeding a waxy wheat. PMID- 8471026 TI - Microsatellite variation in a social insect. AB - We undertook a study to explore the potential of microsatellite loci as genetic markers for investigating kinship patterns in a social wasp Parachartergus colobopterus. A plasmid library with small inserts was screened for several oligonucleotide repeat motifs. Positive clones were sequenced and several were selected for further work. PCR primers were constructed that would amplify the tandem repeat region and a number of female wasps were scored for variation in the number of tandem repeats at these loci. The five amplified loci were far more variable than allozymes, with an average heterozygosity of 0.35. PMID- 8471027 TI - Conformational changes at the active site of creatine kinase at low concentrations of guanidinium chloride. AB - It has been previously reported that, during denaturation of creatine kinase by guanidinium chloride (GdmCl) or urea [Tsou (1986), Trends Biochem. Sci. 11, 427 429], inactivation occurs before noticeable conformational change can be detected, and it is suggested that the conformation at the active site is more easily perturbed and hence more flexible than the molecule as a whole. In this study, the thiol and amino groups at or near the active site of creatine kinase are labelled with o-phthalaldehyde to form a fluorescent probe. Both the emission intensity and anisotropy decrease during denaturation indicating exposure of this probe and increased mobility of the active site. The above conformational changes take place together with enzyme inactivation at lower GdmCl concentrations than required to bring about intrinsic fluorescence changes of the enzyme. At the same GdmCl concentration, the rate of exposure of the probe is comparable with that of inactivation and is several orders of magnitude faster than that for the unfolding of the molecule as a whole. PMID- 8471028 TI - Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia. AB - We have studied the time course and relative effects of hypoinsulinaemia and hyperglycaemia on concentrations of uncoupling protein (UCP) and glucose transporter (GLUT4) and their mRNAs in brown adipose tissue (BAT) during the early phase of diabetes induced by streptozotocin. Two days after intravenous injection of streptozotocin, plasma insulin concentration was at its lowest and glycaemia was higher than 22 mmol/l. After 3 days, a 60% decrease in BAT UCP mRNA concentration and a 36% decrease in UCP was observed. Concomitantly, there was an 80% decrease in GLUT4 mRNA and a 44% decrease in GLUT4 levels. When hyperglycaemia was prevented by infusing phlorizin into diabetic rats, BAT UCP mRNA and protein levels were further decreased (respectively 90% and 60% lower than in control rats). In contrast, the marked decreases in GLUT4 mRNA and protein concentrations in BAT were similar in hyperglycaemic and normoglycaemic diabetic rats. Infusion of physiological amounts of insulin restored normoglycaemia in diabetic rats, and BAT UCP and GLUT4 mRNA and protein concentrations were maintained at the level of control rats. When insulin infusion was stopped, a 75% decrease in BAT UCP mRNA level and a 75% decrease in GLUT4 mRNA level were observed after 24 h, but UCP and GLUT4 concentrations did not decrease. This study shows that insulin plays an important role in the regulation of UCP and GLUT4 mRNA and protein concentrations in BAT. Hyperglycaemia partially prevents the rapid decrease in concentration of UCP and its mRNA observed in insulinopenic diabetes whereas it did not affect the decrease in GLUT4 mRNA and protein concentration. It is suggested that UCP is produced by a glucose-dependent gene. PMID- 8471029 TI - 4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells). AB - Accumulation of quinolinic acid and L-kynurenine occurs in the brain and/or blood following immune activation, and may derive from L-tryptophan following induction of indoleamine 2,3-dioxygenase and other kynurenine-pathway enzymes. In the present study a survey of various cell lines derived from either brain or systemic tissues showed that, while all cells examined responded to interferon gamma by increased conversion of L-[13C6]tryptophan into L-kynurenine (human: B lymphocytes, neuroblastoma, glioblastoma, lung, liver, kidney; rat brain: microglia, astrocytes and oligodendrocytes), only macrophage-derived cells (peripheral-blood mononuclear cells; THP-1, U-937) and certain liver cells (SKHep1) synthesized [13C6]quinolinic acid. Tumour necrosis factor-alpha enhanced the effects of interferon-gamma in THP-1 cells. Norharmane, 6-chloro-DL tryptophan and 4-chloro-3-hydroxyanthranilate attenuated quinolinic acid formation by THP-1 cells with IC50 values of 51 microM, 58 microM and 0.11 microM respectively. Norharmane and 6-chloro-DL-tryptophan attenuated L-kynurenine formation with IC50 values of 43 microM and 51 microM respectively, whereas 4 chloro-3-hydroxyanthranilate had no effect on L-kynurenine accumulation. The reductions in L-kynurenine and quinolinic acid formation are consistent with the reports that norharmane is an inhibitor of indoleamine 2,3-dioxygenase, 6-chloro DL-tryptophan is metabolized through the kynurenine pathway, and 4-chloro-3 hydroxyanthranilate is an inhibitor of 3-hydroxyanthranilate 3,4-dioxygenase. These results suggest that many tissues may contribute to the production of L kynurenine following indoleamine 2,3-dioxygenase induction and immune activation. Quinolinic acid may be directly synthesized from L-tryptophan in both macrophages and certain types of liver cells, although uptake of quinolinic acid precursors from blood may contribute to quinolinic acid synthesis in cells that cannot convert L-kynurenine into quinolinic acid. PMID- 8471030 TI - Evidence for acidity of prelysosomal autophagic/endocytic vacuoles (amphisomes). AB - [14C]Lactose electroinjected into isolated rat hepatocytes is normally autophagocytosed, transferred to lysosomes and degraded by lysosomal beta galactosidase, but at high concentrations of asparagine the transfer is inhibited and lactose accumulates in prelysosomal autophagic/endocytic vacuoles (amphisomes). The accumulation can be prevented by addition of yeast beta galactosidase, which is transferred to the lactose-containing vacuoles by endocytosis. Propylamine, a weak base capable of neutralizing acidic vacuoles, protects autophagocytosed lactose against both endogenous and exogenous beta galactosidase, suggesting that amphisomes, like lysosomes, have an acidic internal environment. PMID- 8471031 TI - Importance of the evolutionarily conserved glycine residue in the N-terminal region of human cystatin C (Gly-11) for cysteine endopeptidase inhibition. AB - Human cystatin C variants in which the evolutionarily conserved Gly-11 residue has been replaced by residues with positively charged (Arg), negatively charged (Glu), bulky hydrophobic (Trp), or small (Ser or Ala) side-chains have been produced by site-directed mutagenesis and expression in Escherichia coli. The five variants were isolated and structurally verified. Their inhibitory properties were compared with those of wild-type recombinant cystatin C by determination of the equilibrium constants for dissociation (Ki) of their complexes with the cysteine endopeptidases papain and human cathepsin B and with the cysteine exopeptidase dipeptidyl peptidase I. The Ser-11 and Ala-11 cystatin C variants displayed Ki values for the two endopeptidases that were approx. 20 fold higher than those of wild-type cystatin C, while the corresponding values for the Trp-11. Arg-11 and Glu-11 variants were increased by a factor of about 2000. In contrast, the Ki values for the interactions of all five variants with the exopeptidase differed from that of wild-type cystatin C by a factor of less than 10. Wild-type cystatin C and the Ser-11, Ala-11 and Glu-11 variants were incubated with neutrophil elastase, which in all cases resulted in the rapid hydrolysis of a single peptide bond, between amino acid residues 10 and 11. The Ki values for the interactions with papain of these three N-terminal-decapeptide lacking cystatin C variants were 20-50 nM, just one order of magnitude higher than the value for N-terminally truncated wild-type cystatin C, which in turn was similar to the corresponding values for the full-length Glu-11, Arg-11 and Trp-11 variants. These data indicate that the crucial feature of the conserved Gly residue in position 11 of wild-type cystatin C is that this residue, devoid of a side-chain, will allow the N-terminal segment of cystatin C to adopt a conformation suitable for interaction with the substrate-binding pockets of cysteine endopeptidases, resulting in high-affinity binding and efficient inhibition. The functional properties of the remaining part of the proteinase contact area, which is built from more C-terminal inhibitor segments, are not significantly affected even when amino acids with bulky or charged side-chains replace the Gly-11 residue of the N-terminal segment. PMID- 8471032 TI - Investigations of the mechanism by which mammalian cell growth is inhibited by N1N12-bis(ethyl)spermine. AB - N1N12-Bis(ethyl)spermine (BESM) and related compounds are powerful inhibitors of cell growth that may have potential as anti-neoplastic agents [Bergeron, Neims, McManis, Hawthorne, Vinson, Bortell and Ingeno (1988) J. Med. Chem. 31, 1183 1190]. The mechanism by which these compounds bring about their effects was investigated by using variant cell lines in which processes thought to be altered by these agents are perturbed. Comparisons between the response of these cells and of their parental equivalents to BESM, N1N11-bis(ethyl)norspermine, N1N14 bis(ethyl)homospermine and N1N8-bis(ethyl)spermidine were then made. It was found that D-R cells, an L1210-derived line that over-expresses ornithine decarboxylase, were not resistant to these compounds. This indicates that the decrease in ornithine decarboxylase is not critical for the action of the compounds on cell growth. Furthermore, although polyamine levels were decreased in the D-R cells, the content was not totally depleted, indicating that such depletion is also not essential for the anti-proliferative effect. Two cell lines lacking mitochondrial DNA (human 143B206 cells and chicken DU3 cells) did not differ in sensitivity to BESM from their parental 143BTK- and DU24 cells. Furthermore, the inhibition of respiration in L1210 cells in response to BESM developed more slowly than the inhibition of growth. Thus it appears that the inhibitions of mitochondrial DNA synthesis and of mitochondrial respiration are also not primary factors in the anti-proliferative effects of these polyamine analogues. The inhibition of growth did, however, correlate with the intracellular accumulation of the analogues. It appears that the bis(ethyl)polyamine derivatives act by binding to intracellular target molecules and preventing macromolecular synthesis. The decline in normal polyamines may facilitate such binding, but is not essential for growth arrest. PMID- 8471033 TI - Hepatic one-carbon metabolism in early folate deficiency in rats. AB - Glycine N-methyltransferase (GNMT) is inhibited by 5-methyltetrahydrofolate polyglutamate in vitro. It is believed to play a regulatory role in the synthesis de novo of methyl groups. We have used the amino-acid-defined diet of Walzem and Clifford [(1988) J. Nutr. 118, 1089-1096] to determine whether folate deficiency in vivo would affect GNMT activity, as predicted by the studies in vitro. Weanling male rats were fed on the folate-deficient diet or a folate-supplemented diet pair-fed to the deficient group. A third group was fed on the folate supplemented diet ad libitum. Development of folate deficiency rapidly resulted in decreased levels of S-adenosylmethionine (SAM) and elevation of S adenosylhomocysteine (SAH). The ratios of SAM to SAH were 1.8, 2.7 and 1.5 in the deficient group for weeks 2, 3 and 4 of the experiment, and the values were 9.7, 7.1 and 8.9 for the pair-fed control group and 10.3, 8.8 and 8.0 for the control group ad libitum fed. The activity of GNMT was significantly higher in the deficient group than in either of the two control groups at each time period. This was not due to increased amounts of GNMT protein, but reflected an increase in specific enzyme activity. Levels of folate in both the cytosol and mitochondria were severely lowered after only 2 weeks on the diet. The distribution of folate coenzymes was also affected by the deficiency, which resulted in a marked increase in the percentage of tetrahydrofolate polyglutamates in both cytosol and mitochondria and a very large decrease in cytosolic 5-methyltetrahydrofolate. The increased GNMT activity is therefore consistent with decreased folate levels and decreased inhibition of enzyme activity. PMID- 8471034 TI - Large changes of transition-state structure during experimental evolution of an enzyme. AB - The question of whether, during the evolution of an enzyme, the transition state of the catalysed reaction is largely unchanged, or whether transition state and protein change together, was examined using the egb beta-galactosidases of Escherichia coli. Charge development at the first chemical state was assumed [Konstantinidis and Sinnott (1991) Biochem. J. 279, 587-593] to be proportional to delta delta G++, the ratio of second-order rate constants for the hydrolysis of beta-D-galactopyranosyl fluoride and 1-fluoro-D-galactopyranosyl fluoride, expressed as a free-energy difference. delta delta G++ (kJ.mol-1) falls from 10.4 for wild-type enzyme to 6.8 and 7.2 as a consequence of two different single amino-acid changes (which arise from single evolutionary events), to 6.3 as a consequence of the two amino-acid changes together, and then increases slightly to 7.3 as a consequence of a third single evolutionary change involving three further amino-acid changes. PMID- 8471035 TI - An overview of the kinetic parameters of class B beta-lactamases. AB - The catalytic properties of three class B beta-lactamases (from Pseudomonas maltophilia, Aeromonas hydrophila and Bacillus cereus) were studied and compared with those of the Bacteroides fragilis enzyme. The A. hydrophila beta-lactamase exhibited a unique specificity profile and could be considered as a rather specific 'carbapenemase'. No relationships were found between sequence similarities and catalytic properties. The problem of the repartition of class B beta-lactamases into sub-classes is discussed. Improved purification methods were devised for the P. maltophilia and A. hydrophila beta-lactamases including, for the latter enzyme, a very efficient affinity chromatography step on a Zn(2+) chelate column. PMID- 8471036 TI - Partial characterization of mechanism(s) by which sulphobromophthalein reduces biliary lipid secretion. AB - This study was performed to explore the mechanisms by which sulphobromophthalein (BSP) reduces the secretion of biliary lipid using Sprague-Dawley rats (SDR) and mutant rats with congenital conjugated hyperbilirubinaemia bred from SDR (EHBR). We infused the bile-salt-pool-depleted rats with sodium taurocholate at a constant rate of 160 nmol/min per 100 g body wt. with BSP (12.5, 25 and 50 nmol/min per 100 g body wt.) or BSP-GSH (12.5, 25 and 50 nmol/min per 100 g body wt.). The biliary secretion of BSP and BSP-GSH was markedly impaired in EHBR as compared with that in SDR. BSP reduced the biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting the secretion of bile salts and composition of fatty acids in phospholipids in SDR, but had no effect on lipid secretion in EHBR. In contrast, BSP-GSH had no such effect on biliary lipids, either in the SDR or EHBR. In addition, the amount of BSP in the liver of EHBR was in the same range as that of SDR. Therefore it is unlikely that an intracellular mechanism is involved in the phenomenon of uncoupling by BSP. We conclude that the uncoupling of biliary lipids from bile-salt secretion by BSP occurs at the level of the bile canaliculus following the secretion of unconjugated BSP. PMID- 8471037 TI - Expression of rat liver ketohexokinase in yeast results in fructose intolerance. AB - Rat liver ketohexokinase (ATP:D-fructose 1-phosphotransferase; EC 2.7.1.3) was purified to homogeneity and the molecular mass of the protein was found by mass spectrometry to be 32,800 Da. The enzyme was cleaved and the amino acid sequences of seven peptides, comprising 24% of the total sequence, were determined. This sequence information was used to design oligonucleotide primers for a PCR using rat liver single-stranded cDNA as a template. The 224 bp PCR product was used as a probe to screen a rat liver cDNA library. A cDNA sequence of 1342 bp was obtained from three positive clones. This contained the entire coding region for ketohexokinase, and all seven peptides were identified in the predicted amino acid sequence. When ketohexokinase was expressed in Saccharomyces cerevisiae using the yeast expression vector pMA91, the cells became intolerant of the presence of fructose in their growth media. The growth of an exponential-phase culture was completely arrested within 90 min by the addition of fructose to a final concentration as low as 0.1% (w/v). This response is associated with an accumulation of fructose 1-phosphate. The cDNA for ketohexokinase encodes a protein composed of 299 amino acids with a combined molecular mass of 32,728 Da. This is in close agreement with the value for the isolated protein determined by mass spectrometry. The primary structure does not show any significant homology with those of other eukaryotic hexokinases, but it contains a highly conserved region that is present in three prokaryotic phosphotransferases that have furanose substrates. PMID- 8471038 TI - Receptor-mediated endocytosis of retinol-binding protein by liver parenchymal cells: interference by radioactive iodination. AB - Retinol-binding protein (RBP) was iodinated directly by radio-iodine substitution on the tyrosyl residues by the sodium hypochlorite (NaOCl) or the Enzymobead (EB) methods, or indirectly by linkage of 125I-tyramine-cellobiose (TC) or 125I-N succinimidyl-3-(4- hydroxyphenyl)propionic acid ester (SHPP) adduct on to free amino residues of RBP. Binding, uptake and degradation of iodinated RBP were studied in isolated rat and rabbit liver parenchymal cells. The amount of ligand bound to cells at 4 degrees C was dependent on the type of labelling, in that the 125I-TC ligand was bound to a lesser extent than NaClO-labelled 125I-RBP, EB labelled 125I-RBP and 125I-SHPP-RBP. At 37 degrees C, the 125I-SHPP-RBP and the EB-labelled 125I-RBP became cell-associated more rapidly than the other two ligands. The higher cell association at 37 degrees C than at 4 degrees C suggests that internalization of the ligand occurred at the higher temperature. The degradation of the ligands was also different. The EB-labelled 125I-RBP, the 125I TC-RBP and the 125I-SHPP-RBP showed an apparent lag phase before a steady increase in acid-soluble radioactivity was observed. Much less of EB-labelled 125I-RBP and 125I-TC-RBP were degraded (about 6%) than of the other two ligands (about 16%) after 120 min. About 50% of the acid-soluble radioactivity in these experiments could be accounted for by degradation in the medium, suggesting that about half of the degradation observed was intracellular. The present study therefore shows that the different labelling techniques yield varying estimates of the cellular handling of RBP. In addition, a rapid release of RBP was observed in experiments where cells were pulsed with radioactive RBP at 4 degrees C, washed and incubated further at 37 degrees C. Between 50% and 70% was released after 5 min of incubation. By increasing the temperature during the pulse to 37 degrees C, or by lowering the temperature during the chase to 4 degrees C, much less RBP was released from the cells. These data suggest that the release process represents recycling of internalized ligand from an early endosome. PMID- 8471039 TI - Immunological and biochemical characterization of processing products from the neurotensin/neuromedin N precursor in the rat medullary thyroid carcinoma 6-23 cell line. AB - Neurotensin (NT) and neuromedin N (NN) are two related biologically active peptides that are encoded in the same precursor molecule. In the rat, the precursor consists of a 169-residue polypeptide starting with an N-terminal signal peptide and containing in its C-terminal region one copy each of NT and NN. NN precedes NT and is separated from it by a Lys-Arg sequence. Two other Lys Arg sequences flank the N-terminus of NN and the C-terminus of NT. A fourth Lys Arg sequence occurs near the middle of the precursor and is followed by an NN like sequence. Finally, an Arg-Arg pair is present within the NT moiety. The four Lys-Arg doublets represent putative processing sites in the precursor molecule. The present study was designed to investigate the post-translational processing of the NT/NN precursor in the rat medullary thyroid carcinoma (rMTC) 6-23 cell line, which synthesizes large amounts of NT upon dexamethasone treatment. Five region-specific antisera recognizing the free N- or C-termini of sequences adjacent to the basic doublets were produced, characterized and used for immunoblotting and radioimmunoassay studies in combination with gel filtration, reverse-phase h.p.l.c. and trypsin digestion of rMTC 6-23 cell extracts. Because two of the antigenic sequences, i.e. NN and the NN-like sequence, start with a lysine residue that is essential for recognition by their respective antisera, a micromethod by which trypsin specifically cleaves at arginine residues was developed. The results show that dexamethasone-treated rMTC 6-23 cells produced comparable amounts of NT, NN and a peptide corresponding to a large N-terminal precursor fragment lacking the NN and NT moieties. This large fragment was purified. N-Terminal sequencing revealed that it started at residue Ser23 of the prepro-NT/NN sequence, and thus established the Cys22-Ser23 bond as the cleavage site of the signal peptide. Two other large N-terminal fragments bearing respectively the NN and NT sequences at their C-termini were present in lower amounts. The NN-like sequence was internal to all the large fragments. There was no evidence for the presence of peptides with the NN-like sequence at their N termini. This shows that, in rMTC 6-23 cells, the precursor is readily processed at the three Lys-Arg doublets that flank and separate the NT and NN sequences. In contrast, the Lys-Arg doublet that precedes the NN-like sequence is not processed in this system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8471040 TI - A novel post-translational modification of the peptide antibiotic subtilin: isolation and characterization of a natural variant from Bacillus subtilis A.T.C.C. 6633. AB - A variant of the peptide antibiotic subtilin has been isolated from Bacillus subtilis A.T.C.C. 6633, and its structure has been shown to be [N alpha-succinyl Trp1]subtilin. The chemical structure of a fragment derived by tryptic hydrolysis of the variant is shown to be N alpha-succinyl-Trp-Lys by 1H and 13C n.m.r., fast atom-bombardment m.s. and total chemical synthesis [N alpha-Succinyl-Trp1] subtilin is produced later in the growth of the bacterium than is subtilin; reverse-phase h.p.l.c. analysis shows that after 24 h growth the ratio subtilin/[N alpha-succinyl-Trp1]subtilin is approx. 1:2. Although [N alpha succinyl-Trp1]subtilin retains significant antibacterial activity, it is 10-20 times less active than subtilin. PMID- 8471041 TI - Biosynthesis, surface expression and function of the fibronectin receptor after rat liver cell transformation to tumorigenicity. AB - Zajdela hepatoma cells are poorly-adherent cells derived from an undifferentiated tumour and transplanted into rat. We compared the biosynthesis, structure and function of the fibronectin receptor in normal rat hepatocytes with that in Zajdela hepatoma cells. The rat hepatocyte fibronectin receptor has been isolated. It is composed of two subunits: alpha 5 (molecular mass 155 kDa) and beta 1 (molecular mass 115 kDa). However, its biosynthesis has not yet been described. Using polyclonal antibodies raised against each of the subunits of the receptor, we observed that the alpha 5-subunit was synthesized as a 155-kDa polypeptide in normal rat hepatocytes and Zajdela hepatoma cells. In contrast, the molecular mass of the beta 1-subunit was 130 kDa in Zajdela hepatoma cells versus 115 kDa in normal rat hepatocytes. Pulse-chase experiments showed that the apparent transition time from the 100-kDa beta 1-precursor to the 130-kDa mature form was abnormally prolonged in Zajdela hepatoma cells since the latter was not detected until 24 h, while the transition from the 100-kDa precursor to the 115 kDa mature form began within 3 h in normal rat hepatocytes. Digestion of both the normal rat hepatocytes and Zajdela hepatoma cells 100-kDa beta 1-precursors with endo-beta-N-acetylglucosaminidase H and peptide N-glycosidase yielded products from 100 kDa to 84 kDa and 82 kDa, respectively, as judged by SDS/PAGE, suggesting that the same polypeptide chain is synthesized in normal rat hepatocytes and in Zajdela hepatoma cells. Incubation of the mature normal rat hepatocyte beta 1-subunit with peptide N-glycosidase reduced its molecular mass from 115 kDa to 82 kDa, as judged by SDS/PAGE, while the molecular mass of the abnormal mature Zajdela hepatoma cell beta 1-subunit decreased from 130 to 110 kDa. Thus, in addition to alterations in the Asn-linked oligosaccharide processing, 'ascitic growth' induced other post-translational modifications in the Zajdela hepatoma cell beta 1-subunit. Furthermore, both the abnormal mature 130-kDa and precursor 100-kDa beta 1-subunits were detected on the surface of Zajdela hepatoma cells, associated with the alpha 5-subunit. The relationship between these structural alterations in the fibronectin receptor and the impaired Zajdela hepatoma cell binding to soluble fibronectin or to a coated fibronectin matrix that was observed in this study is discussed. PMID- 8471042 TI - Expression of the glucose transporter GLUT4 in the muscular dystrophic mdx mouse. AB - Glucose transporter protein levels have been investigated in mdx and control (C57Bl/10) mice. Crude membrane fractions (microsomes plus plasma membranes) were prepared from skeletal muscle, heart, diaphragm and brain of 5-6-week-old and 6-7 month-old control and mdx mice. Using Western blot analysis with C-terminal specific anti-peptide antibodies, we investigated the glucose transporters GLUT4 in the different muscle tissues and GLUT1 in brain. In skeletal tissue from the hindlegs, GLUT4 was increased by approximately 55% in mdx mice compared with control mice at both ages studied. In the diaphragm, the amount of GLUT4 protein was unchanged in young mdx mice, and was decreased by 37.4 +/- 4.7% in older mice compared with age-matched control mice. No difference was observed between mdx and control mice in the amounts of GLUT4 and GLUT1 in heart and brain preparations respectively. To determine whether the change in GLUT4 protein observed in the diaphragm and skeletal muscle of mdx mice was regulated through changes at the level of glucose transporter mRNA, Northern blot analyses were performed. In skeletal muscle, GLUT4 mRNA level per tissue was not different between the two groups of mice at both ages studied. In contrast, the decrease in the amount of GLUT4 protein observed in the diaphragm of 6-7-month-old mdx mice was accompanied by a decrease in the GLUT4 mRNA level. In conclusion, the levels of GLUT4 protein were modified in muscle tissues from mdx compared with control mice, and these modifications were different depending on the muscle involved and the age of the mice. An increase in the amount of GLUT4 protein in the skeletal muscle of mdx mice was not due to changes at the mRNA level. The diaphragms of 6 7-month-old mdx mice exhibited decreases in GLUT4 protein and mRNA levels that were not detected in young animals (5-6 weeks old). PMID- 8471043 TI - Differential effects of spermine and its analogues on the structures of polynucleotides complexed with ethidium bromide. AB - The interactions of spermine and polyamine analogues with synthetic polynucleotides of various base sequences complexed with ethidium bromide (EB) were investigated using measurements of fluorescence intensity and steady-state fluorescence polarization. Spermine and polyamine analogues displaced some but not all of the EB bound to poly(dA-dT).poly(dA-dT) or poly(dG-dC).poly(dG-dC), suggesting that polyamines may stabilize these polynucleotides in a conformation with reduced affinity for EB. Modifications of the aliphatic backbone of spermine have pronounced effects on its ability to displace EB from poly(dA-dT).poly(dA dT) but not from poly-(dG-dC).poly(dG-dC). Spermine and some but not all of the polyamine analogues caused fluorescence depolarization when they interacted with the complex of EB and poly(dA-dT).poly-(dA-dT). Neither spermine nor any of the analogues, however, induced fluorescence depolarization in the complex of EB with poly(dG-dC).poly(dG-dC) or poly(dA).poly(dT). This suggests that spermine and some spermine analogues induce structural changes specific to alternating A-T sequences. PMID- 8471044 TI - Purification, sequence and antibacterial activity of two novel sapecin homologues from Sarcophaga embryonic cells: similarity of sapecin B to charybdotoxin. AB - Two sapecin homologues were purified from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina (flesh fly). These homologues contained six cysteine residues with exactly the same disulphide pairings as those in sapecin. The amino acid sequence of one of them, sapecin C, was also very similar to that of sapecin. The other homologue, sapecin B, was less similar to sapecin but showed significant similarity to charybdotoxin, an inhibitor of K+ channels isolated from a scorpion venom. Like sapecin, these homologues repressed the growth of various Gram-positive bacteria. PMID- 8471045 TI - Haemin enhancement of glucose transport in human lymphocytes: stimulation of protein tyrosine phosphatase and activation of p56lck tyrosine kinase. AB - Following our previous observation that haemin is mitogenic for human lymphocytes, we investigated the ability of haemin to enhance glucose uptake in these cells. We found that preincubation of human peripheral-blood mononuclear cells (PBMC) with haemin for 60 min increased up to 5-fold the rate of 2-deoxy-D [1-3H]glucose uptake by the cells. Actinomycin D and cycloheximide did not inhibit the effect, and cytochalasin B completely blocked it. Among the metalloporphyrins tested (Fe-, Ni-, Co-, Zn- and Sn-protoporphyrin), only haemin (Fe-protoporphyrin) induced a marked increase in glucose uptake. Thiourea, a scavenger of oxygen free radicals, and 3-amino-1,2,4-triazole inhibited haemin induced glucose uptake. Oxidants such as H2O2 and phenylarsine oxide were previously reported to stimulate protein tyrosine phosphorylation and to enhance glucose uptake. We found that incubation of PBMC with haemin resulted in an increase in protein tyrosine phosphatase (PTPase) activity, probably that identified as CD45. Similarly to haemin, we found that phytohaemagglutinin also enhanced PTPase activity. Haemin also activated the tyrosine kinase p56lck, which is negatively controlled by phosphorylation of Tyr-505 at the C-terminus, and increased protein tyrosine phosphorylation in these cells. Tyrphostins, specific inhibitors of tyrosine kinases, at low concentrations markedly enhanced glucose uptake and synergized with haemin in enhancing glucose uptake. At high doses, tyrphostins inhibited the effect of haemin. Taken together, we postulate that haemin enhancement of glucose uptake in human lymphocytes results from its stimulation of PTPase, followed by activation of tyrosine kinase p56lck, leading to an increase in protein tyrosine phosphorylation. PMID- 8471046 TI - Reconstitution in vitro of the pH-dependent aggregation of pancreatic zymogens en route to the secretory granule: implication of GP-2. AB - Regulated secretory proteins are thought to be sorted in the trans-Golgi network (TGN) via selective aggregation. To elucidate the biogenesis of the secretory granule in the exocrine pancreas, we reconstituted in vitro the conditions of pH and ions believed to exist in the TGN using the end product of this sorting process, the zymogen granule contents. Protein aggregation was dependent on pH (acidic) and on the presence of cations (10 mM Ca2+, 150 mM K+) to reproduce the pattern of proteins found in the granule. The constitutive secretory protein IgG was excluded from these aggregates. Zymogen aggregation correlated with the relative proportion of the major granule membrane protein GP-2 in the assay. These results show that the glycosylphosphatidylinositol-anchored protein GP-2 co aggregates with zymogens in the acidic environment believed to exist in the pancreatic TGN, and thus suggest that GP-2 would function as a membrane anchor for zymogen aggregates, facilitating their entrapment in budding vesicles directed towards the regulated secretory pathway. PMID- 8471047 TI - Genetic variation of iron-induced uroporphyria in mice. AB - Iron overload causes inhibition of hepatic uroporphyrinogen decarboxylase (UROD) and uroporphyria in C57BL/10ScSn but not DBA/2 mice [Smith, Cabral, Carthew, Francis and Manson (1989) Int. J. Cancer 43, 492-496]. We have investigated the induction of uroporphyria in 12 inbred strains of mice 25 weeks after iron treatment (600 mg/kg) to determine if there was any correlation with the Ah locus. Under these conditions, inhibition of UROD occurred to varying degrees in Ahd mice (SWR and AKR) as well as nominally Ahb-1 (C57BL/6J, C57BL/10ScSn and C57BL/10-cc) and Ahb-2 strains (BALB/c and C3H/HeJ). Five other Ahb or Ahd strains (C57BL/Ks, A/J, CBA/J, LP and DBA/2) were unaffected. Thus there appeared to be no correlation with the Ah phenotype and this illustrated that some other variable inherited factors are involved. Comparisons between another susceptible strain, A2G, and the congenic A2G-hr/+strain (carrying the recessive hr gene) showed a modulating influence associated with the hr locus. In contrast with individual mice of inbred strains, which showed consistent responses to iron, those of the outbred MF1 strain showed a spectrum of sensitivities as might be expected for a heterogeneic stock. The rate of porphyria development was accelerated by administration of 5-aminolaevulinic acid (5-ALA) in the drinking water, but this did not overcome strain differences. Among four strains the order of susceptibility was SWR > C57BL/10ScSn > C57B1/6J > DBA/2 (the last strain was completely resistant). With degrees of iron loading greater than 600 mg of Fe/kg (1200-1800 mg of Fe/kg) C57BL/10ScSn mice (after 20 weeks) and SWR mice (after 5 weeks which included 4 weeks of 5-ALA treatment) had less inhibition of UROD and a lower uroporphyric response, showing that there was an optimum level of liver iron concentration. Studies on selected microsomal enzyme activities associated with cytochrome P-450 showed no correlation with the propensities of strains to develop porphyria. These activities included the NADPH-dependent oxidation of uroporphyrinogen I to uroporphyrin I. PMID- 8471048 TI - Active transport of L-proline in the protozoan parasite Trypanosoma brucei brucei. AB - The characteristics of L-proline transport in the procyclic form of Trypanosoma brucei were studied by using L-[14C]proline and a quick separation technique by centrifugation through an oil mixture. L-Proline uptake displayed typical Michaelis-Menten kinetics, with a Km of 19 microM and a maximum transport velocity of 17 nmol/min per 10(8) cells at 27 degrees C. The maximum concentration gradient factor obtained after 1 min of incubation was 270-fold in 0.02 mM proline. Cells permeabilized with 80 microM digitonin were still able to accumulate 14C label, but to a lower extent. The temperature-dependence of proline uptake gave an apparent activation energy of 74.9 kJ.mol-1. In competition studies with a 10-fold excess of structural analogues, L-alanine, L cysteine and L-azetidine-2-carboxylate were found to inhibit L-proline uptake. Variation of pH or addition of the protonophore carbonyl cyanide m chlorophenylhydrazone ('CCCP') did not affect proline transport, showing that it is not driven by a protonmotive force. The absence of Na+, with or without monensin, did not affect proline transport. The absence of K+ and the addition of the Na+,K(+)-ATPase inhibitor ouabain had no significant effect on proline uptake activity. The thiol-modifying reagent iodoacetate (10 mM) decreased proline uptake by half. KCN (1 mM) inhibited proline uptake to a lesser extent, and the degree of inhibition was proportional to the intracellular ATP concentration. Preliminary experiments on proline transport in plasma-membrane vesicles of the cells, using a filtration technique, showed an uptake of proline (0.67 nmol/mg of protein) by the vesicles, but only in the presence of intravesicular ATP. The results thus obtained suggest that the proline carrier system in T. brucei is ATP driven and independent of Na+, K+ or H+ co-transport. PMID- 8471049 TI - Specificity constants for two-substrate reactions. PMID- 8471050 TI - Enzyme specificity in reactions of more than one co-substrate. PMID- 8471051 TI - Is there an alternating site co-operativity between the two subunits of lamb liver 6-phosphogluconate dehydrogenase? PMID- 8471052 TI - Deduced amino acid sequence, gene structure and chromosomal location of a novel human class Mu glutathione S-transferase, GSTM4. AB - The Mu-Class glutathione S-transferases (GSTs) are subject to marked inter individual variation in man, owing to the fact that 40-50% of the population fail to express M1 subunits. Mu-Class GST from two lymphoblastoid cell lines (expressing M1 subunits and the other 'nulled' for M1) have been studied. Both cell lines were found to express a Mu-Class GST that has not been described previously. The cDNA encoding this novel transferase, designated 'GSTM4' has been isolated and the enzyme shown to be comprised of 218 amino acids (including the initiator methionine residue) with an M(r) of approx. 25.5 kDa. Molecular cloning demonstrated that the lymphoblastoid cell line which expressed GSTM1 possessed the b allelic variant (i.e. that with an asparagine residue at position 173). The genes for GSTM4 and GSTM1b have been cloned and found to contain seven introns and eight exons. The coding region of the GSTM4 gene, including the seven introns, encompasses 5.0 kb, whereas the same region of GSTM1b is 5.5 kb; the difference in the size of the two genes is due to the length of intron 7. DNA sequencing allowed a GSTM4-gene-specific oligo-primer to be designed which has been utilized in a PCR-based assay to determine that the GSTM4 gene is located on chromosome 1. PMID- 8471053 TI - A simple purification of procyclic acidic repetitive protein and demonstration of a sialylated glycosyl-phosphatidylinositol membrane anchor. AB - The procyclic acidic repetitive protein is the major cell-surface glycoprotein of the insect-dwelling procyclic forms of the Trypanosoma brucei species of African trypanosomes. The glycoprotein contains an acidic Glu-Pro repeat domain, a glycosyl-phosphatidylinositol membrane anchor and a putative asparagine glycosylation site. In this paper we describe a rapid purification scheme for this glycoprotein, using solvent extraction and hydrophobic interaction chromatography, and a partial characterization of the glycosylphosphatidylinositol membrane anchor. The carbohydrate composition of the anchor is extremely unusual; it contains on average nine GlcNAc, nine Gal, and five sialic acid residues. This is the first description of such a heavily substituted and negatively charged anchor. A comparison between the trypanosome procyclic surface and the Leishmania promastigote surface is also presented. PMID- 8471054 TI - A specific binding of the cholecystokinin-releasing peptide (monitor peptide) to isolated rat small-intestinal cells. AB - A specific binding of the cholecystokinin (CCK)-releasing peptide (monitor peptide) to isolated rat jejunal mucosal cells was investigated. The 125I labelled purified monitor peptide bound to the rat jejunal cells, and a large excess amount of the non-labelled monitor peptide inhibited the binding. The binding was completed within 60 min at 37 degrees C. The optimum pH for the binding was 8-9. A Scatchard plot of the specific binding was linear, and the dissociation constant was 50 nM. The density of the monitor-peptide-binding sites was high in duodenum but low in ileal and absent in colonic mucosa. A recombinant monitor peptide and four kinds of point mutants of it were prepared. The binding of the mutant monitor peptides to the cells indicated that only a trypsin inhibitor of the mutants could bind to the mucosal cells. Human pancreatic secretory trypsin inhibitor inhibited the specific binding, but other trypsin inhibitors, i.e. bovine basic pancreatic trypsin inhibitor, soybean trypsin inhibitor, egg-white trypsin inhibitor, leupeptin, antipain and FOY-305, did not affect the specific binding at all. These findings suggested that the specific binding site for the monitor peptide on the jejunal mucosal cells has a trypsin like specificity, exhibiting a special specificity for the pancreatic-secretory trypsin-inhibitor family. Autoradiography of an affinity-cross-linked complex of the 125I-labelled intact monitor peptide and the binding site suggested that its molecular mass was 33 kDa or 53 kDa in the presence or absence of 2 mercaptoethanol respectively. PMID- 8471055 TI - Lipoamidase activity in normal and mutagenized pancreatic cholesterol esterase (bile salt-stimulated lipase). AB - Purified human milk lipoamidase was digested with endoproteinase Lys-C and the digested peptides were subjected to gasphase microsequence analysis. The sequencing of three isolated peptides of human milk lipoamidase revealed the identity of this protein with human milk bile salt-stimulated lipase (pancreatic cholesterol esterase). The identity of the cholesterol esterase with lipoamidase was confirmed by expressing a recombinant form of rat pancreatic cholesterol esterase and testing for lipoamidase activity of the recombinant protein. The results showed that the recombinant cholesterol esterase displayed both lipolytic and lipoamidase activities and was capable of hydrolysing triacetin and lipoyl-4 aminobenzoate (LPAB). The mechanisms of the esterase and amidase activities of the enzyme were further tested by determining enzyme activity in a mutagenized cholesterol esterase with a His435-->Gln435 substitution. This mutation has been shown previously to abolish enzyme activity against esterase substrates [DiPersio, Fontaine and Hui (1991) J. Biol. Chem. 266, 4033-4036]. We showed that the mutagenized protein was effective in hydrolysing the amidase substrate LPAB and displayed similar enzyme kinetics to those of the native enzyme. These data indicate that the mechanism for the cholesterol esterase hydrolysis of lipoamides is different from that of the hydrolysis of substrates with an ester linkage. The presence of an enzyme in the gastrointestinal tract capable of both ester and amide hydrolysis suggests an important role for this protein in the digestion and absorption processes. PMID- 8471056 TI - Role of the C-terminal domain of pulmonary surfactant protein A in binding to alveolar type II cells and regulation of phospholipid secretion. AB - Surfactant protein A (SP-A), with a reduced denatured molecular mass of 26-38 kDa, is characterized by a collagen-like sequence in the N-terminal half of the protein. This protein forms an oligomeric structure which is dependent upon this collagenous domain. SP-A has been demonstrated to function as an inhibitor of phospholipid secretion by primary cultures of alveolar type II cells via a cell surface receptor for the protein. However, the receptor-binding domain of SP-A has not been identified. The purpose of the present study was to investigate the role of the C-terminal domain of SP-A in binding to type II cells and regulation of phospholipid secretion. A monoclonal antibody to human SP-A, whose epitope was localized at the C-terminal domain of the protein, abolished the inhibitory activity of human SP-A on lipid secretion by type II cells, and attenuated the ability of human SP-A to compete with 125I-(rat SP-A) for receptor binding. SP-A was then digested with collagenase and the collagenase-resistant fragment (CRF), which is the C-terminal domain of SP-A (thus lacking the N-terminal domain), was isolated. Gel filtration chromatography revealed that CRF exists as a monomer in solution containing Ca2+. CRF had the ability to inhibit phospholipid secretion, although at a higher concentration than for SP-A, and was also able to compete with 125I-(rat SP-A) for binding to type II cells. A direct binding study showed that CRF bound to type II cells in a concentration-dependent manner. The present study demonstrates that the non-collagenous, C-terminal, domain of SP-A is responsible for the protein's inhibitory effect on lipid secretion and its binding to type II cells. PMID- 8471058 TI - When cells take fate into their own hands: differential competence to respond to inducing signals generates diversity in the embryonic mesoderm. PMID- 8471057 TI - Localization and hormonal stimulation of phosphorylation sites in the LNCaP-cell androgen receptor. AB - Phosphorylation of the androgen receptor in human prostate tumour cells (LNCaP) is increased by addition of androgens to intact cells. Double-label studies, using [35S]methionine incorporation into receptor protein, and [32P]P(i) to label metabolically receptor phosphorylation sites, have enabled us to determine the phosphate content, relative to receptor protein, of both nontransformed and transformed and androgen receptors generated in intact LNCaP cells. No net change in the phosphorylation of the intact 110 kDa steroid-binding component of the androgen-receptor complex was found upon transformation to the tight nuclear binding form in the intact cell. Partial proteolysis of androgen receptor protein metabolically labelled with [32P]P(i) and photolabelled with [3H]R1881 (methyltrienolone) revealed that phosphorylation occurs mainly in the N-terminal trans-activation domain, whereas no phosphorylation was detected in the steroid- and DNA-binding domains. The location of most (> 90%) of the hormonally regulated phosphorylation sites in the N-terminal trans-activation domain suggests a role of phosphorylation of the androgen receptor in transcription regulation. PMID- 8471059 TI - Microdissection and microcloning of human chromosome regions in genome and genetic disease analysis. PMID- 8471060 TI - Translational regulation by mRNA/protein interactions in eukaryotic cells: ferritin and beyond. AB - The expression of certain eukaryotic genes is--at least in part--controlled at the level of mRNA translation. The step of translational initiation represents the primary target for regulation. The regulation of the intracellular iron storage protein ferritin in response to iron levels provides a good example of translational control by a reversible RNA/protein interaction in the 5' untranslated region of an mRNA. We consider mechanisms by which mRNA/protein interactions may impede translation initiation and discuss recent data suggesting that the ferritin example may represent the 'tip of the iceberg' of a more general theme for translational control. PMID- 8471061 TI - In pursuit of the functions of the Wnt family of developmental regulators: insights from Xenopus laevis. AB - Wnts are a recently described family of secreted glycoproteins related to the Drosophila segment polarity gene, wingless, and to the proto-oncogene, int-1. Wnts are thought to function as developmental modulators, with signalling distances of only a few cell diameters. In Xenopus, at least six Wnts, including Xwnts-1, -3A, and -4, are expressed initially in the developing central nervous system, with some regions expressing multiple Xwnts. Xwnt-8 is expressed by mid blastula stage, in ventral and lateral mesoderm. Xwnt-5A mRNAs are stored in the egg, and later are expressed throughout the embryo in both ectoderm and mesoderm, but with a pronounced enrichment in the head and tail. Recent studies in Xenopus have pursued the diverse roles of Xwnts in early development, the mechanisms by which Xwnts signal information between cells, and the cell physiological responses to Xwnt signals. PMID- 8471062 TI - Environmental regulation of virulence factors in Bordetella species. AB - Many bacteria respond in a coordinate manner to environmental changes. External stimuli, sensed by receptors, are transduced to regulatory proteins which participate in well defined pathways of gene expression by varying their structure and mode of action. The network of environmental signal transduction is responsible for a fine and continuous communication between the host and the pathogenic bacteria. As a result, the gene expression machinery of the pathogen is modified continuously, in order to establish the optimal conditions for bacterial survival and multiplication. PMID- 8471063 TI - Transplacental transfer of polychlorinated biphenyls induces simultaneously the expression of P450 isoenzymes and the protooncogenes c-Ha-ras and c-raf. AB - At day 15 of gestation, rats were injected with a single i.p. dose of 100, 250 and 500 mg/kg body weight of a mixture of polychlorinated biphenyls (PCBs) (Aroclor 1254). Seven days later, significant increases in maternal and foetal cytochrome P450, cytochrome b5 and cytochrome c (P450) reductase were found. Concomitantly, the metabolism of nitroanisole, aniline, ethoxyresorufin and benzo[a]pyrene was significantly increased, but foetal metabolism of dimethylnitrosamine was not detectable and only marginal increases in the metabolism of aminopyrine and aldrin were seen. In contrast, maternal metabolism of dimethylnitrosamine, aminopyrine and aldrin was measurable, but significant increases were determined only with the latter substrate. Transplacental transfer of PCBs resulted in increased metabolism of substrates catalysed by foetal CYP1A1 and CYP2B1, but there was no evidence for CYP2E1-catalysed reactions. Further measurements show significant increases in foetal and maternal epoxide hydrolase, glutathione-S-transferase and UDP-glucuronyl transferase activities, thus suggesting that treatment with Aroclor 1254 resulted in coordinated increases in foetal and maternal oxidative and post-oxidative drug metabolism. Western blot analysis of microsomal proteins shows the induction of foetal and maternal CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP3A1 and CYP4A1. In addition, increased expression of CYP2C6 was seen with the mother but not the foetus. Unlike the mother, foetal rats did not express CYP2E1 and the expression of the above-listed P450 isoenzymes was greater in the mother than the foetus. Northern blot analysis shows significant increases in maternal and foetal CYP1A1, CYP1A2 and CYP2B1 mRNA. An increased amount of CYP3A1 mRNA was only seen with the mother, but not the foetus. Treatment of mothers with Aroclor 1254 resulted in reduced CYP2A1, CYP2C7, CYP2E1 and CYP4A1 mRNA. Insignificant differences in the expression of foetal CYP2A1 and CYP4A1 mRNA were found, but in utero exposure to PCBs reduced the amounts of CYP2E1 mRNA and there was no foetal CYP2C7 mRNA transcript. Treatment with Aroclor 1254 increased the expression of the protooncogenes c-Ha ras and c-raf in the mother and the foetus, but at varying intensities. Pregnancy itself was linked to an increased expression of these protooncogenes. erbA and erbB mRNA was not detected. PMID- 8471064 TI - Identification of the fragment photoaffinity-labeled with azidodansyl-rhizoxin as Met-363-Lys-379 on beta-tubulin. AB - The rhizoxin (RZX)-binding site on porcine brain tubulin was investigated by photoaffinity labeling with the 5-azido-1-naphthalene sulfonyl (azidodansyl) derivative of RZX, nor-rhizoxin-22-al-5'-azidonaphthalene-1'-sulfonylhydrazo ne (azidodansylrhizoxin: Adan-RZX). Upon ultraviolet irradiation, Adan-RZX generates a highly reactive nitrene, which irreversibly binds to an amino acid residue(s) near the RZX-binding site. The label was found to be on beta-tubulin. Enzymatic digestion of the labeled tubulin generated only one major fluorescent peak on C18 reverse phase HPLC analysis. The labeled site(s) was mapped by using various combinations of highly specific peptidases in succession. That is, the labeled fragment generated by the first peptidase was purified by HPLC and exposed to a second peptidase; if the retention time in HPLC changed after the second digestion, the fragment generated in the first digestion must have contained the recognition site(s) of the second enzyme. From the results of these successive digestions and the known polypeptide sequences, we could identify the labeled fragment as Met-363-Lys-379 of beta-tubulin. This peptidase combination technique should be widely applicable. PMID- 8471065 TI - Tissue- and subunit-specific regulation of G-protein expression by hypo- and hyperthyroidism. AB - Thyroid hormone status has profound effects on signal transduction in various tissues throughout the body. Therefore, we quantified the signal transducing G proteins in the rat heart, cerebral cortex, vas deferens and liver by immunoblotting and pertussis toxin labeling in response to chemically induced hypothyroidism (treatment with propylthiouracil) and hyperthyroidism (treatment with triiodothyronine). Levels of the pertussis toxin (PTX) substrates Gi alpha and Go alpha in the heart and vas deferens were inversely correlated with thyroid hormone levels, i.e. Gi alpha and Go alpha were decreased or unchanged in hyperthyroid rats and increased in hypothyroid rats compared to control animals. The cerebral cortex and liver expression of PTX substrates Gi alpha and Go alpha was not affected by changes in thyroid hormone. Regulation of Gs alpha protein was more complex in that Gs alpha was unaffected in the other tissues tested. Expression of G-protein beta-subunits was not affected by thyroid status in the heart, liver, or cerebral cortex. Our results suggest that tissue- and G-protein specific factors are involved in the regulation of G-protein subunits by thyroid hormone. Moreover, cardiac expression of Gs alpha is upregulated by increases or decreases in the normal level of thyroid hormone. PMID- 8471066 TI - Production of an interleukin-8-like chemokine by cytokine-stimulated rat NRK-49F fibroblasts and its suppression by anti-inflammatory steroids. AB - Normal rat kidney fibroblasts (NRK-49F cells) stimulated with interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) produced mainly cytokine induced neutrophil chemoattractant (CINC) which is the rat counterpart of human gro/melanoma growth stimulatory activity. In addition, the cytokine-stimulated cells produced two minor neutrophil chemoattractants which are highly related to murine macrophage inflammatory protein-2 in their NH2-terminal amino acid sequences. IL-1 beta was a stronger stimulator than TNF-alpha, and addition of both the cytokines into the NRK-49F cell culture caused an additive stimulation for rat gro/CINC production. The anti-inflammatory steroids (dexamethasone, prednisolone and hydrocortisone) at 10(-9)-10(-6) M significantly suppressed the production of rat gro/CINC by the IL-1 beta-stimulated NRK-49F cells in a dose dependent manner. The relative potencies of the inhibitory activity of the steroids on the rat gro/CINC production were dexamethasone > prednisolone > hydrocortisone. On the other hand, the non-steroidal anti-inflammatory drugs (indomethacin and piroxicam) at 10(-7)-10(-5) M showed no apparent inhibitory effect on rat gro/CINC production by NRK-49F cells stimulated with IL-1 beta. PMID- 8471067 TI - Malaria pigment and extracellular iron. Possible target for iron chelating agents. AB - Extracellular iron is necessary for many biochemical reactions involved in Plasmodium falciparum growth and multiplication. The incorporation of radioactive iron taken up by the parasite was found, electrophoretically and via gamma counting, to be mainly associated with the haemozoin only in the presence of the active metabolism of the parasite. The potent antimalarial activity of desferrioxamine, a ferric iron chelating agent, has shown that iron deprivation is inhibitory to the parasite. We propose that the mechanism of action of desferrioxamine in addition to the chelation of iron from the parasitic compartment, chelates iron from the haemozoin crystal resulting in free radical generation and parasite death. The ability of desferrioxamine and not the ferrous iron chelating agent, 2,2'-bipyridyl, to chelate the non-haem iron from the haemozoin structure indicates that the oxidative state of iron associated with the haemozoin structure is ferric in nature. PMID- 8471068 TI - Role of thyroid state on induction by ciprofibrate of laurate hydroxylase and peroxisomal enzymes in rat liver microsomes. AB - The effects of hypothyroidism and hyperthyroidism upon liver microsomal omega laurate hydroxylase activity (cytochrome P450 IV A1-dependent), peroxisome proliferation marker enzyme activities and acyl CoA oxidase (AOX) expression induced by ciprofibrate (2 mg/kg/day during 8 days) were studied in the male Wistar rat so as to clarify firstly the possible involvement of thyroid hormones in the modification of peroxisomal ciprofibrate-induced enzyme activities in relation to hepatic microsomal cytochrome P450 IV A1 induction, and secondly the possible direct effect of thyroid hormones on the gene expression of specific peroxisomal enzymes. No significant change was found in the ciprofibrate-induced omega-laurate hydroxylase activity in hypothyroid rats or in rats that had received a large dose of triiodothyronine (LT3), suggesting that the thyroid hormone does not interfere with the peroxisome proliferation process through such an indirect mechanism. The induction by ciprofibrate [2-(4-(2 2dichlorocyclopropyl)phenoxyl-2methyl-propion ic acid)] of mitochondrial alpha glycerolphosphate dehydrogenase and microsomal bilirubin UDPGT was decreased about 3-fold and 1.5-fold, respectively, while the induction of peroxisomal AOX, carnitine acetyl transferase and enoyl CoA hydratase enzyme activities was decreased by 36%, 34% and 22% in thyroidectomized animals, as compared to euthyroid animals. However, no significant changes in the quantity of peroxisomal proteins and in the AOX mRNA level were noted. The administration of large doses of LT3 to normal rats decreased the peroxisomal ciprofibrate AOX enzyme induction with a marked concomitant decrease in the AOX mRNA level. This suggests that high doses of LT3 enhance the turnover of some specific mRNAs or down regulate the peroxisome proliferator receptor. Our results also do not exclude inhibition of catabolic activity towards AOX which depends on thyroid hormone. PMID- 8471069 TI - Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F. AB - Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level. Also after 5 min, TBARS (thiobarbituric acid reactive substances, a color test for lipid peroxidation) showed a statistically significant (P < or = 0.05) increase that continued through the remainder of the 30-min experiment. Reduced protein thiols decreased significantly (P < or = 0.05) at 15 min post FAS addition. This suggests that, in this model of iron-initiated lipid peroxidation (LP), the endogenous antioxidant vitamin E is first depleted before membrane lipids and membrane bound proteins show evidence of oxidative injury. A novel antioxidant, U-78517F, inhibited the destruction of vitamin E, LP and protein thiol oxidation in this model. The efficacy of the compound after different times of addition is described. PMID- 8471070 TI - Induction of P4502E1 by acetone in isolated rabbit hepatocytes. Role of increased protein and mRNA synthesis. AB - The molecular mechanism(s) underlying induction of the hepatic microsomal cytochrome P4502E1 (2E1) by xenobiotics (e.g. ethanol and acetone) is controversial. Proposed mechanisms include increased rates of enzyme synthesis due to elevated 2E1 mRNA levels, enhanced translation of pre-existing mRNA, or stabilization of 2E1 protein. To further assess which, if any, of these events predominates during the initial stages of 2E1 protein induction, we investigated the effects of acetone treatment on 2E1 content in cultured rabbit hepatocytes, an in vitro system that allows for precise control of the cellular mileau. Hepatocytes harvested from female rabbits and plated on plastic dishes with serum supplemented medium were 90-100% viable for at least 48 hr in culture. Analysis of immunoreactive 2E1 content and aniline hydroxylase activity in microsomes isolated from hepatocytes cultured for up to 24 hr revealed that 2E1 expression was equal to that of microsomes from unplated cells and by 48 hr of culture, 2E1 levels decreased by only 35%. Moreover, microsomes isolated from cells exposed to 17 mM acetone for 24 hr exhibited a 53 and 62% increase in aniline hydroxylase activity and 2E1 content, respectively, compared to untreated cells. To explain these increases, the rate of 2E1 protein synthesis was determined in untreated cells or in cells treated with 17 mM acetone by first exposing hepatocytes to medium supplemented with 35S-labeled methionine and cysteine ([35S]Met/Cys) and subsequently assessing radiolabel incorporation into 2E1 protein. While no difference was found between untreated and acetone-treated cells in the incorporation of [35S]Met/Cys into trichloracetic acid-precipitable microsomal proteins, immunoaffinity purification of 2E1 revealed that incorporation of 35S labeled amino acids specifically into 2E1 was elevated by acetone to 200% of control values. Treatment of hepatocytes with the transcriptional inhibitor, alpha-amanitin, markedly inhibited this acetone-mediated increase in [35S]Met/Cys incorporation into 2E1. Analysis of hepatocyte RNA revealed that acetone increased 2E1 mRNA to 130 and 160% of control levels at 6 and 24 hr, respectively, and that these increases were prevented by pretreatment with alpha amanitin. Our results indicate that acetone increases 2E1 protein levels in cultured rabbit hepatocytes by stimulating its rate of de novo synthesis. Since this increase in 2E1 synthesis stems, at least in part, from the acetone-mediated enhancement of hepatocyte 2E1 mRNA content and is inhibitable by alpha-amanitin, transcriptional activation of the rabbit CYP2E1 gene is apparently involved in the induction of 2E1 protein by acetone. PMID- 8471071 TI - Mechanism of resistance to cyclopentenyl cytosine (CPE-C) in Molt-4 lymphoblasts. AB - Cyclopentenyl cytosine (CPE-C), a carbocyclic analogue of cytidine, has preclinical antineoplastic activity against ara-C resistant murine leukemias and a broad spectrum of human tumor xenografts. CPE-C is a prodrug and requires intracellular phosphorylation to cyclopentenyl cytosine triphosphate (CPE-CTP) which depletes endogenous CTP pools. The initial step in this activation process is catalyzed by uridine/cytidine kinase. We studied the mechanism of resistance to CPE-C in a Molt-4 T-cell leukemia line made resistant to CPE-C (Molt-4R) by culturing it in the continuous presence of increasing concentrations of CPE-C. Using a tetrazolium based colorimetric assay to assess cytotoxicity, the IC90 for the parent Molt-4 cells (Molt-4WT) was 0.5 microM after a 24 hr drug exposure. In contrast, cytotoxicity was not observed at concentrations as high as 1 mM in the Molt-4R cells. Following a brief exposure to 1 microM CPE-C, parent drug could be detected intracellularly in the resistant and sensitive cell lines. However, CPE CTP formation was reduced markedly in the resistant cell line. Measurement of the activity of anabolic and catabolic enzymes in the Molt-4WT and Molt-4R cells revealed equivalent activities of alkaline and acid phosphatases as well as cytidine and dCMP deaminase but there was a significant reduction in uridine/cytidine kinase activity in Molt-4R cells. Endogenous ribonucleotide pools and CPE-CTP pools were measured in the absence and presence of CPE-C. CTP pools were reduced markedly in Molt-4WT cells following exposure to CPE-C. However, CTP pools in Molt-4R cells exposed to 100 microM CPE-C were two times greater than in the untreated Molt-4WT cells. At high concentrations of CPE-C (10 and 100 microM), Molt-4R cells were able to generate amounts of CPE-CTP equivalent to that seen in Molt-4WT cells exposed to 1 microM CPE-C (a cytotoxic concentration of drug in Molt-4WT cells), but no cytotoxic effect was seen in Molt-4R cells. Therefore, in addition to decreased uridine/cytidine kinase activity, a second mechanism of resistance that is the result of alterations in CTP synthetase activity also appears to be operative. Elucidation of the mechanism of resistance in vitro may provide insight into the mechanism of action of the drug and potential mechanisms of resistance in vivo. PMID- 8471072 TI - Differential effects of active isomers, segments, and analogs of dolastatin 10 on ligand interactions with tubulin. Correlation with cytotoxicity. AB - Dolastatin 10 is a potent antimitotic peptide isolated from the marine mollusk Dolabella auricularia. Four of its five residues are modified amino acids (in sequence, dolavaline, valine, dolaisoleuine, dolaproine, dolaphenine). Besides inhibiting tubulin polymerization, dolastatin 10 non-competitively inhibits vinca alkaloid binding to tubulin, inhibits nucleotide exchange and formation of the beta s cross-link, and stabilizes the colchicine binding activity of tubulin. To examine the mechanism of action of dolastatin 10 we prepared six chiral isomers, one tri- and one tetrapeptide segment, and one pentapeptide analog of dolastatin 10, all of which differ little from dolastatin 10 as inhibitors of tubulin polymerization. However, only two of the chiral isomers were similar to dolastatin 10 in their cytotoxicity for L1210 murine leukemia cells and in their effects on vinblastine binding, nucleotide exchange, beta s cross-link formation, and colchicine binding. These were isomer 2, with reversal of configuration at position C(19a) in the dolaisoleuine moiety, and isomer 19, with reversal of configuration at position C(6) in the dolaphenine moiety. The pentapeptides with reduced cytotoxicity and reduced effects on tubulin interactions with other ligands were all modified in the dolaproine moiety at positions C(9) and/or C(10). The tripeptide and tetrapeptide segments which inhibited polymerization but not ligand interactions were the amino terminal tripeptide (lacking dolaproine and dolaphenine) and the carboxyl terminal tetrapeptide (lacking dolavaline). We speculate that strong inhibition of other ligand interactions with tubulin requires stable peptide binding to tubulin (i.e. slow dissociation), but that inhibition of polymerization requires only rapid binding to tubulin. PMID- 8471073 TI - Effect of tocotrienol on the activities of cytosolic glutathione-dependent enzymes in rats treated with 2-acetylaminofluorene. AB - The effect of tocotrienol on the activities of glutathione S-transferases (GSTs), glutathione reductase (GR) and glutathione peroxidase (GPx) in rats given 2 acetylaminofluorene (AAF) was investigated over a 20 week period. Liver and kidney GST and liver GR activities were significantly increased after AAF administration. Kidney GPx activities were significantly affected; activity assayed with cumene hydroperoxide (cu-OOH) was increased but activity assayed with H2O2 was reduced. Supplementation of the diet with tocotrienol in the AAF treated rats reduced the increase in enzyme activities. Tocotrienol on its own had no effect on the enzyme activities. PMID- 8471074 TI - Comparative study of active absorption by the intestine and disposition of anomers of sugar-conjugated compounds. AB - Active absorption in the intestine and metabolism of the beta- and alpha-anomers of the glucoside and galactoside of p-nitrophenol (p-NP) were studied to find a more suitable prodrug for poorly absorbed drugs. The everted sac technique was used to investigate the intestinal absorption of these glycosides at 250 microM from the mucosal to the serosal side in the rat jejunum. The absorption clearance of p-nitrophenyl alpha-D-glucopyranoside (p-NP alpha glc) (0.271 +/- 0.089 microL/min/cm, mean +/- SE, N = 8) was much lower than that of p-nitrophenyl beta D-glucopyranoside (p-NP beta glc) (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4) which is actively absorbed by a glucose transport carrier [Mizuma et al., Biochem Pharmacol 43: 2037-2039, 1992]. However, the major constituent appearing on the serosal side was p-NP (aglycone) after absorption of pNP alpha glc, whereas it was p-NP beta glc itself after absorption of p-NP beta glc. The total amount transported to the serosal side after 20 min of p-NP alpha glc absorption, which was similar to that of p-NP beta glc, was significantly decreased in the absence of Na+, indicating the active absorption of p-NP alpha glc by a Na(+) dependent glucose transport carrier. Perfusion with a mucosal solution of p-NP alpha glc showed that the p-NP concentration on the serosal side (15.8 +/- 1.56 microM, mean +/- SE, N = 3) was significantly (P < 0.05) higher than that on the mucosal side (5.84 +/- 1.24 microM, mean +/- SE, N = 3) at 20 min. This indicated that the p-NP appearing on the serosal side was derived not from absorption of p NP but from hydrolysis of p-NP alpha glc through the intestinal membrane during absorption. On the other hand, after absorption of p-nitrophenyl beta-D galactopyranoside (p-NP beta gal), which is actively absorbed by glucose transport carrier, p-NP beta gal itself appeared mostly on the serosal side. However, p-nitrophenyl alpha-D-galactopyranoside (p-NP alpha gal) absorption, which resulted in appearance on the serosal side, was not significantly decreased in the presence of 1 mM phloridzin or in the absence of Na+, indicating that the contribution of the glucose transport carrier to p-NP alpha gal absorption was minimal. The order of the Na(+)-dependent intestinal absorption was p-NP beta glc > p-NP alpha glc > p-NP beta gal > p-NP alpha gal. PMID- 8471075 TI - Degradation of angiotensin I in the endothelium and smooth muscle of the rat aorta. AB - In homogenates of the endothelium and smooth muscle cum adventitia of the rat aorta, exogenous angiotensin (ANG) I was found to be degraded to des-aspartate ANG I (des-Asp-ANG I) instead of ANG II. ANG II and ANG III were not detectable in either of the homogenates after 5, 10 and 30 min of incubation with the decapeptide. However, both the homogenates were able to catalyse hippuryl-L histidyl-L-leucine (HHL) to hippuric acid and the catalysis was completely inhibited by 3 microM captopril. The data show that the angiotensin converting enzyme (ACE) present in the homogenates of rat aorta, prepared by normal laboratory procedures, is not able to hydrolyse ANG I to ANG II. This finding has important consequences in the study of vascular ACE as the assay of the enzyme is often carried out using crude homogenate and HHL or other artificial substrates. In addition, the aminopeptidase that degraded ANG I to des-Asp-ANG I was not inhibited by either amastatin or bestatin, indicating that it was not aminopeptidase A or B. Together with the recent findings of other investigators which show that the de novo production of ANG II in vascular tissues is stimulated and inhibited by beta- and alpha-agonists, respectively, our present data may suggest that production of vascular ANG II occurs only in intact tissues and is probably under adrenergic regulation. PMID- 8471076 TI - Kinetic analysis of mutual metabolic inhibition of lidocaine and propranolol in rat liver microsomes. AB - The metabolic interaction between lidocaine (LD) and propranolol (PL) was analysed kinetically in rat liver microsomes. Employing a very short incubation time of 30 sec, we demonstrated that PL competitively inhibited liver microsomal 3-hydroxylation of LD, but did not affect either the formation of monoethylglycinexylidide or methylhydroxylidocaine from LD in PL concentrations up to 1 microM. On the other hand, LD competitively inhibited PL 4-, 5- and 7 hydroxylations, but the inhibition type of LD for PL N-desisopropylation could not be clarified. Comparison of the kinetic data for liver microsomes from Wistar and Dark Agouti rats indicated that among the primary metabolic pathways of LD, the Vmax value for 3-hydroxylation was markedly less in female Dark Agouti rats. The results suggest that LD 3-hydroxylation and PL ring hydroxylations are mediated by the same isozyme(s) belonging to the CYP2D subfamily. PMID- 8471077 TI - Lack of discrimination between DNA ligases I and III by two classes of inhibitors, anthracyclines and distamycins. AB - We have measured the effects of eight distamycin and two anthracycline derivatives on polynucleotide joining and self-adenylating activities of human DNA ligase I and rat DNA ligases I and III. All test drugs show good inhibitory activity against the three enzymes in the poly[d(A-T)] joining assay. Several distamycins also inhibit the DNA-independent self-adenylation reaction catalysed by the human enzyme and, to a lesser extent, by rat DNA ligases. These results confirm that anthracyclines and distamycins express their inhibitory action against DNA joining activities mainly via specific interactions with the substrate, and suggest that the three test DNA ligases utilize similar, if not identical, mechanisms of recognition and interaction with DNA-drug complexes. Our findings also indicate that distamycins have a greater affinity for human DNA ligase I than for rat enzymes, suggesting that, in this respect, rat DNA ligase I is more similar to rat DNA ligase III than to human DNA ligase I. PMID- 8471078 TI - Clinical pharmacokinetics of antidepressants in the elderly. Therapeutic implications. AB - The prevalence of depression in the elderly suggests that a substantial number of older patients will be treated with an antidepressant medication such as one of the tricyclics, trazodone, fluoxetine or lithium. The physiological changes that accompany aging raise the possibilities of altered pharmacokinetics, patterns of efficacy and adverse effect profiles. The literature addressing the subject of antidepressant use in the elderly has not provided a clear, consistent picture of how these drugs behave in this population in comparison with younger patients. Particularly in the case of the tricyclic antidepressants (TCAs), a large degree of interindividual variation in drug clearance (CL) confounds attempts to find differences attributable to age per se. Study design, however, is also a problem in that very few investigators include a young control group, choosing instead to compare their data with previously reported outcomes. Designations of statistical significance and positive correlation also differ among investigators, and the clinical significance of any finding is not always addressed. The available data suggest that imipramine CL is reduced in the elderly and that amitriptyline CL may be reduced. Desipramine CL does not appear to be affected by age, although decreased renal function in the elderly may lead to accumulation of the hydroxylated metabolite, the clinical importance of which is not known. Nortriptyline is the most thoroughly studied TCA in the elderly. CL seems decisively lower only in elderly patients with concurrent medical illness. The hydroxylated metabolite probably accumulates with diminishing renal function. Not enough data are available on doxepin to make a conclusion. Trazodone CL is diminished somewhat in elderly men. Lithium CL appears to diminish with the declining renal function associated with aging. Fluoxetine data are sparse. Available data do not show any decrease in CL of the parent drug; more information is needed on the metabolite norfluoxetine. Although knowledge of CL changes with aging can help the clinician more accurately achieve the desired steady-state concentration of a drug during long term therapy, much work is still needed to evaluate the relationships among drug concentrations at steady-state, efficacy and adverse effects in the elderly. PMID- 8471079 TI - Alcohol consumption and alcohol-related problems in Afro-Caribbeans and south Asians in the United Kingdom. AB - Data from published sources and unpublished surveys in the U.K. show that average alcohol consumption is lower in Afro-Caribbean men and women than in native British men and women. The proportion of heavy drinkers is also low in Afro Caribbeans. Consistent with these consumption data, hospital admission rates for alcohol-related problems are lower in Afro-Caribbeans than in the general population. Among South Asians (Indians, Pakistanis and Bangladeshis) average alcohol consumption is lower than in the native British population but alcohol related morbidity rates for some South Asian communities are higher than for the general population. The reasons for these high morbidity rates are not clear. Consumption is higher in Sikhs than in Hindus or Muslims, and heavy spirit drinking appears to be especially common among Sikh men. Alcohol-related psychiatric admission rates for South Asians have risen since 1971, and appear to be especially high in Sikh men. The high alcohol-related morbidity rates in this group are a priority for further research and efforts at prevention. PMID- 8471080 TI - Detection of antibodies to acetaldehyde-albumin conjugates in alcoholic liver disease. AB - The principal metabolite of ethanol, acetaldehyde, conjugates with various proteins that form antibody-inducing neo-antigens. We have analysed sera from patients with biopsy-proven alcoholic liver disease (hepatitis = 10, cirrhosis = 11, steatosis = 3) and controls = 19 (normal teetotallers and 6 non-alcoholic liver disease). Sera were examined with an enzyme-linked immunoabsorbent assay (ELISA) for antibodies binding preferentially to an acetaldehyde-albumin conjugate. Reactive sera from alcohol misusers were then purified using an amino hexyl Sepharose affinity column. Antibodies binding to the acetaldehyde-albumin epitopes were significantly raised (P < 0.005) in all groups of alcohol misusers, and were present in greatest titre in those with alcoholic hepatitis. These antibodies were successfully purified using the gel affinity column. We conclude that alcohol misusers have significant titres of antibodies reacting to the acetaldehyde-albumin complex. The role of these antibodies remains nuclear, but may be related to the initiation of an inflammatory response and tissue damage following ethanol consumption. PMID- 8471081 TI - Antioxidant status and alcohol-related diseases. AB - Chronic ethanol consumption is associated with increased incidence of a variety of illnesses, including cancer. Studies have shown that ethanol consumption may result in increased oxidative stress with formation of lipid peroxides and free radicals. The susceptibility of a given tissue to peroxidation is, however, a function of the overall balance between prooxidants and antioxidant defence systems. The latter involve both intracellular and extracellular protective factors were nutrients play an important role. Impaired nutritional status of different vitamins and trace elements have been reported in alcoholics. Reduced levels of vitamin E have been found in serum of alcoholics with and without liver disease and in liver biopsies from alcoholics with cirrhosis. These findings may be due to the increased oxidative stress as reported in experimental animals, and may be of importance since vitamin E is the major, if not the only, lipid-soluble free radical scavenger in some tissues. Reduced antioxidant capacity has been found in several tissues and may promote the generation of free radicals and lipid peroxides which may damage cells directly, induce inflammation and accelerate collagen synthesis. These events may progress to tissue damage and disease. The importance of radicals in cancer initiation and promotion is presently of great interest. The role of lipid peroxides and free radicals in alcohol-related disease and cancer remains unresolved. Further research is required to establish the role of these reactive species in the pathogenesis of alcohol-related disease, and to evaluate the role of nutrition in favour of the antioxidant defence mechanisms. PMID- 8471082 TI - Modulation of cancer growth by vitamin E and alcohol. AB - Seventy-five percent of esophageal cancers are alcohol related, yet alcohol is not a carcinogen. Ethanol may promote carcinogenesis via increased free radical products during its metabolism, as indicated by data from this and other studies. Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, catalase and the microsomal ethanol oxidizing system (MEOS). Free radicals (FR) are released during the oxidation of ethanol by the MEOS. An increased formation of FR in tissues would increase their oxidative stress and may increase their susceptibility for developing chemically induced cancers. FR and some FR products can rapidly react with biological materials, i.e. lipids, proteins and nucleic acids, forming toxic products. This study focuses on the effects of FR and/or FR products on cancer promotion during alcohol metabolism. Eight groups of mice were fed nutritionally adequate diets supplemented with vitamin E and/or ethanol. Some groups of mice were also orally gavaged with N-nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen. Following the feeding of the various diets for 22 weeks, livers and esophagi were removed and the FR burden in the liver measured by the presence of lipid peroxide products and the number of tumors in each esophagus determined. These studies indicate that a linear relationship exists between the increasing number of esophageal tumors and increasing levels of lipid peroxide products that are formed during FR activity. These results show that FR and/or FR products are the cancer promoters during ethanol metabolism, since diets supplemented with high levels of vitamin E, which inhibits ethanol-induced FR activity and the formation of FR products, suppress the promotion of cancer by ethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471083 TI - Studies on the chronopharmacology of ethanol. AB - Male subjects (n = 10) were given ethanol (0.75 g/kg) at four equally spaced times in the 24 hr cycle (9 am, 3 pm, 9 pm 3 am) in random order. Blood ethanol concentrations were monitored by breath analysis and measurements were made of the blood or plasma levels of ethanol, acetaldehyde, acetate, pyruvate, lactate and cortisol. Blood pressure, heart rate and body temperature were measured before and at 60 and 120 min after ethanol administration and the effects of ethanol on a number of behavioural parameters and mood were studied. After ethanol ingestion, there was a significant decrease in body temperature, systolic blood pressure, plasma cortisol and pyruvate levels, whilst acetate levels and the lactate:pyruvate ratio were significantly increased. Standing steadiness, critical flicker fusion threshold and divided attention tracking control were significantly impaired under ethanol and self-report data indicated a significant decrease in alertness, co-ordination, concentration and attentiveness. Although a significantly higher peak blood ethanol concentration was attained at the 9 am session, other time-of-day differences did not reach significance and the pharmacokinetics of ethanol were essentially unchanged. Since the only significant diurnal variations in the response to ethanol identified in this study (apart from the subjective results) were for plasma cortisol concentrations and body temperature (both of which are well known to exhibit diurnal rhythmicity), it appears that major circadian variability in the metabolic and/or behavioural effects of ethanol is unlikely to occur. PMID- 8471084 TI - Mathematical modelling of ethanol metabolism in normal subjects and chronic alcohol misusers. AB - The time course of ethanol disappearance from the blood has been examined in normal males and females and in alcohol misusers. Blood alcohol estimations were made over a period of 3 hr, following an oral dose of ethanol (0.8 g/kg body weight) administered in the form of whisky. Attempts were made to fit the data to zero order, first order and mixed zero + first order kinetics. In the majority (75%) of normal females the blood ethanol concentrations was still increasing at 30 min. This was only seen in 50% of normal males and in 50% of non-dependent alcohol misusers, but not in dependent alcohol misusers. In all of the normal females the disappearance of ethanol could be adequately described by zero order kinetics. However, in the normal male group only 20% could be described by zero order kinetics, 10% fitted first order kinetics and the remainder required a mixed model of zero + first order. The rate constant for the zero order component of the control male group was identical to zero order rate constant obtained for the female control group. In the female alcohol misuser group, 40% of the curves could not be described by zero order kinetics and fitted best to a mixed model. The zero order component of the entire group was significantly increased (by 35%) compared to that obtained for the female control group. In the male dependent and non-dependent alcohol misuser groups, all blood alcohol concentration curves fitted best to mixed zero and first order kinetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471085 TI - The Alcohol Use Disorders Identification Test (AUDIT) and the SMAST-13: predictive validity in a rural primary care sample. AB - This study was conducted to compare the validity of a new screening instrument developed by the World Health Organization, the Alcohol Use Disorders Identification Test (AUDIT), to the short version of the MAST in 287 primary care patients. Subjects were classified as meeting a lifetime or current DSM-III diagnosis of alcohol misuse and/or dependence based on the DIS-R interview schedule. Using the original WHO guidelines (score of 11 or more), 37 (13%) scored positive on the AUDIT and 103 (36%) had a weighted score of 5 or more on the SMAST-13. The internal reliability of the AUDIT was 0.86, compared to the SMAST-13 at 0.85. Cut-off scores in this sample for current alcohol problems, utilizing Receiver Operating Curves, were 7-8 for the AUDIT and 5 for the SMAST. This study confirms the utility of the AUDIT for current alcohol problems and the SMAST-13 for lifetime or past problems in a rural clinical sample. PMID- 8471086 TI - Patterns of alcohol consumption among the general population of Castile and Leon (Spain). AB - A total of 2500 individuals, aged 14-70, who live in Castile and Leon (Spain), were surveyed in the spring of 1989 with regard to their alcohol consumption and its patterns. Among those surveyed 26.2% were 'daily' drinkers and 66.0% 'weekly' drinkers. Differences of alcohol use (frequency) and intake were reviewed with regard to sociodemographic factors such as gender, age, and marital status. Beer (52.6%) was the favourite drink, with wine (20.6%) the second most commonly consumed alcohol beverage. Most of those surveyed (54.6%) were 'light' drinkers (1-39 g/day of pure alcohol), while 3.0% had an intake of over 80 g/day ('heavy' drinkers). The average age at which they started drinking was 16.2 years. The results allow a better understanding of the pattern of alcohol consumption in Spain. PMID- 8471087 TI - Alcohol-nutrient interactions: a critical component of physiological change. PMID- 8471088 TI - Dietary fatty acids and alcohol: effects on cellular membranes. AB - The consumption of ethanol has been shown to exert profound effects on cellular membranes which result in damage and/or adaptation. Both membrane lipids and proteins are affected, but because of the physicochemical properties of ethanol, many of the membrane effects are directly related to the interaction of ethanol with the lipid component of the membrane. In addition to the direct lipid-ethanol interaction, ethanol has been shown to dramatically alter lipid metabolism. Triacylglycerol accumulates dramatically in the liver, and biosynthesis of the polyunsaturated fatty acids seems to be altered via effects upon the acyl-CoA desaturases. Because precursors of both families of unsaturated fatty acids, i.e. omega 3 and omega 6 families, cannot be synthesized de novo, they must be supplied from dietary sources. Thus, the unsaturated membrane fatty acid composition depends upon these dietary fats and their metabolism via the desaturases. Further, the level of dietary fat seems to play a very important role in ethanol-induced damage to various cellular membranes. Diets with high levels of fat greatly enhance liver steatosis as well as liver membrane damage and liver fibrosis. By altering the composition of dietary fat to include either more saturated fatty acids, higher levels of a specific omega 6 fatty acid, alpha linolenic acid, or higher levels of the omega 3 fatty acids, biochemical, physiological and neurobehavioral effects of ethanol have been shown to be modulated. Therefore, it appears that dietary fatty acids may play an important role in altering some of the deleterious effects of ethanol. PMID- 8471089 TI - Ethanol and diet-induced alterations in Kupffer cell function. AB - The effects of 6 weeks of alcohol feeding on phagocytic, metabolic and secretory functions as well as gene expression of hepatic Kupffer cells were evaluated in vitro using cultured Kupffer cells isolated from male Sprague-Dawley rats. The rats were fed either Teklad pelleted rat chow or the 1982 Lieber-DeCarli liquid diet containing 6% ethanol (36% calories) or the same liquid diet with maltose dextrin isocalorically substituted for the alcohol. Weight gain was greatest in the chow-fed animals and least in those receiving ethanol. The alcohol-containing diet stimulated Kupffer cell phagocytosis, mitochondrial reduction of MTT, secretion of tumor necrosis factor (TNF) and expression of TNF mRNA. However, each of these cell functions was also enhanced by the control Lieber-DeCarli liquid diet alone and the stimulating effect of the control diet often exceeded that induced by ethanol. The results suggest that early in chronic alcohol consumption, the immune system may be stimulated by ethanol, and that during studies of ethanol-induced changes in immune system function, close attention must be given to potentially confounding effects of the diet. PMID- 8471090 TI - Nutrient intake and nutritional status in alcoholics. AB - The modern techniques used in making reliable nutritional surveys and in assessing the nutritional status of alcoholic individuals have greatly improved our possibilities to determine the nutrient intake and to detect nutritional deficiencies in alcoholics from different social groups. In earlier studies, the rather high incidence of malnutrition in alcoholics can be related to the patients consisting of indigent, skid row alcoholics or patients with severe somatic complications. Later studies have revealed that nutritional deficiencies are rare among middle-class alcoholics without significant somatic complications. However, selective nutritional deficiencies may be found among lower-income and homeless alcoholic populations. PMID- 8471091 TI - Role of nutrients in alcohol-induced immunomodulation. AB - Immunosuppression observed in chronic alcohol users is caused by multiple factors including the amount of alcohol consumed and alcohol-induced nutritional deficiencies. Investigators of the immunotoxic effects of ethanol (ETOH) frequently concentrate on the effects of ETOH and neglect nutrition as a confounding variable. This study investigated the immunotoxic effects of ETOH under variable dietary nutritional conditions. Mice were fed diets containing various levels of nutrients and ethanol for 7 weeks. Spleen cell number, and interleukin-2 and tumor necrosis factor (TNF) secretion were independent of the diet consumed, but were affected by consumption of ETOH. Body and spleen weights, and interferon-gamma secretion were modulated by ETOH as well as by diet. The results indicate that the nutritional composition of the diet consumed during concurrent administration of ETOH modulates the immunotoxic effects of chronic ETOH ingestion. We conclude that the levels of various nutrients in animal diets have to be planned and controlled carefully in order to identify directly the immunotoxic effects of ETOH. PMID- 8471092 TI - Nutrition in the pathogenesis of alcoholic liver disease. AB - The data and experimental results reviewed here allow the construction of the following hypothesis: alcohol-induced liver disease results from a combination of two phenomena. The first is the induction of the maximum activity of CYP 2E1 by several dietary factors, i.e. (1) low carbohydrate-high fat diet; and (2) the dietary fats composed of PUFA (Yang et al., 1992). The second is the production of lipid peroxidation induced by CYP 2E1 oxidation of ethanol maintained at high blood alcohol levels (> 200 mg %) with the availability of PUFA as substrate (Ekstrom and Ingelman-Sundberg, 1988; Koop, 1992). Thus, lipid peroxidation may be the final common pathway which supports the induction of ALD. Further, it may provide the common denominator which links ALD pathogenesis to non-alcoholic steato-hepatitis (NASH) (French et al., 1989b), where CYP 2E1 is induced by high fat diet and/or diabetes (Dong et al., 1988). PMID- 8471093 TI - [The therapeutic value of ambulatory extracorporeal shockwave lithotripsy of salivary calculi. Results of a prospective study]. AB - In a prospective study, results of the extracorporeal shock wave lithotripsy of salivary stones were evaluated. The study was performed with the currently available technical possibilities of electromagnetic systems to get indication criteria for this procedure. Using the Modulith SL 20-lithotripter of Storz Medical AG, 33 concrements in 25 patients were treated in 89 lithotripsy sections. The stone sizes, localized by ultrasound, ranged from 3 to 13 mm diameter (phi 6.9 mm). After application of local anaesthesia, per session on an average 1300 shock waves with raising energy levels were applied, the succession of shocks fixed to 1 MHz. With the help of ultrasound localisation, a therapeutic success with complete emission of the concrement or an adequate disintegration of these stones could be achieved in 82% of the parotid gland stones (n = 11) and in 14% of the submandibular gland stones (n = 22). Since the unhampered functioning of these salivary glands is an inevitable pre-condition for the spontaneous emission of the disintegrated fragments, the status of function of salivary glands should be established by a scintigraphy before performing the ESWL. Even though complete emission of the stone could be achieved in only 4 patients, all patients were clinically free of symptoms after the treatment. In 3 of 25 patients, discrete bleeding of a passing nature occurred coming from the salivary duct. In 2 patients, formation of haematoma of varying dimensions could be visualized by ultrasound. 3 patients showed petechial skin bleeding. The tinnitus aurium which affected one patient eased after 3 days. In our patients collective a facial nerve damage did not occur.2+ longterm prognosis after this procedure. PMID- 8471094 TI - [Magnetic resonance angiography--a new procedure for vascular imaging in the area of the head-neck]. AB - Some six or seven years ago, digital subtraction angiography (DSA) was introduced as a new diagnostic tool in the evaluation of vascular lesions. In the diagnostic management of vascular disorders in the head and neck, DSA could replace conventional angiography almost completely. Now, a new angiographic technique has been developed--magnetic resonance angiography (MRA). In the present study 60 patients with vascular lesions of head and neck were examined with both DSA and MRA in order to compare the diagnostic value of these techniques. Our results indicate that MRA is at least equivalent in the evaluation of vascular disorders in head and neck region. In addition, the advantages of MRA compared to DSA are the following: (1) MRA is a non-invasive technique, thus reducing the angiographic risk. (2) MRA offers the possibility of multiplanar imaging. (3) MRA can be performed simultaneously with MRI if necessary. (4) Compared to other angiographic techniques the patient will not be exposed to radiation. PMID- 8471095 TI - [Acoustic rhinometry: measuring the early and late phase of allergic immediate reaction in allergic rhinitis]. AB - Acoustic rhinometry is a method to analyse nasal airway geometry. Almost every antigen-induced allergic reaction in the nasal cavity leads to morphologic changes known as nasal obstruction. Therefore a study in 8 patients suffering from allergic rhinitis was conducted. Patients were challenged with 1,000 Biological Units (BU) of grass pollen or D. pteronyssinus extract in one nostril. Acoustic rhinometry (AR) was performed before and 10, 20, 30, 45 and 60 minutes and then 2 to 8 hours after allergen exposure. 4 of the patients developed a late phase reaction. Changes were seen in the minimal cross-sectional area (MCA) and even better in a newly induced volume parameter called volume A (V-A). Volume A is calculated by integration of the distance/area graph surrounding the anterior part of the lower turbinate. Thus we can get information on more than one point of a graph in the important region of the anterior nose. Early phase reaction leads to a decrease in both MCA and V-A from 30% to 10% of the baseline value whereas late phase reaction gives only a third of this effect. The contralateral V-A and MCA are only slightly affected in the early phase, but there is an almost symmetric reaction of both sides in the late phase reaction. All changes were more pronounced in V-A compared to MCA. Therefore we propose to add V-A to MCA in describing the results of AR. Acoustic rhinometry is a suitable method for measuring local changes following nasal allergen challenge. PMID- 8471096 TI - [The viral and allergic origin of nasal polyposis]. AB - In spite of recent advances in basic science, the etiology and pathogenesis of nasal and paranasal polyps have still not been clarified. Well-defined causal factors are hereditary diseases such as cystic fibrosis and primary ciliary dyskinesia. Allergic and non-allergic processes of the airways, particularly intrinsic asthma and intolerance to non-steroidal antiinflammatory drugs, are implicated in the development of nasal polyposis. In the 1930s nasal polyps were strongly considered to be a manifestation of allergy. The theory was challenged in the 1970s. Many patients with nasal polyps have no identifiable allergic disease. The cause of nasal polyps is speculative. 221 patients were included in this study, 154 suffering from chronic rhinosinusitis and another 46 from nasal polyps. The incidences of aspirin intolerance and of allergy were of no statistic relevance. The data indicate that preoperative cortisone application does improve the disease-free interval. PMID- 8471097 TI - [The Nikolowski trichoadenoma: a rare tumor of the ENT area]. AB - A case of trichoadenoma Nikolowski in a 74-year-old woman is reported. The tumour invaded the upper lip, the base of the columella and the left nasal entrance. The tumour was cured by surgery and plastic reconstruction of the defect. This benign lesion of the hair follicles is rare and therefore often misdiagnosed as basal cell carcinoma or seborrheic keratosis. Examination of tumour cells by DNA-flow cytophotometry showed a normal diploid DNA-content of the tumour cells. PMID- 8471098 TI - [Morphometric evaluation of connective tissue reaction to cartilage implants]. AB - In this paper, besides already investigated cartilage implants, we studied morphologically and histometrically possibilities to use human thyroid cartilage in reconstructive surgery, especially in nasal septum and pyramid reconstructions. Preserved human thyroid and rib cartilage as well as rabbit preserved rib cartilage were implanted under the back skin of 12 New Zealand rabbits. Animals were divided into two groups with 6 specimens in each group followed 6 and 12 weeks after implantation. Beside morphological investigation we measured histometrically the thickness of connective capsule around implants. Results obtained by our morphological and histometric studies indicate that preserved human thyroid cartilage could be used in reconstructive surgery with the same success as other cartilage implants already used. PMID- 8471099 TI - [Cartilage transplantation in the area of the head-neck: comparative study of HLA class II antigen induction to chondrocytes in various culture systems]. AB - Autologous and homologous cartilage grafts are often used in reconstructive head and neck surgery. Unfortunately, sometimes the outcome of such operations is endangered by graft rejection or resorption. Among other reasons, immunological reactions with HLA class II antigen expression are thought to be involved at least in failures of vitally grafted cartilage. Up to now, only one case of class II antigen expression in a cartilage graft "in vivo" has been reported. Nevertheless, it has already been demonstrated that stimulated cartilage cells are able to express "in vitro" class II antigens if grown in monolayer cultures. However, it has also repeatedly been shown that chondrocytes reveal strong dedifferentiating features if cultured in monolayers. Therefore, it was the aim of this study to examine whether isolated and stimulated chondrocytes also express class II antigens if cultured under in vitro conditions closer to the relevant in vivo situation. Hence monolayer, suspension, agar, alginate and organ cultures were prepared simultaneously and kept for up to 60 days. Chondrocytes were stimulated by the addition of IFN-gamma and tested for class II antigens. For the detection of the antigens immunocyto- and immunohistochemical APAAP stainings as well as flow cytometric measurements were made. In all examined culture systems a class II antigen induction could be observed. Any significant differences between the various cultures as to the intensity of antigen expression could not be detected. Consequently, the expression of class II antigens on stimulated human chondrocytes seems not to be a specificity of monolayer cultures. Therefore, class II antigen induction may be considered to play a role in the rejection/resorption of vitally grafted cartilage in reconstructive surgery. PMID- 8471100 TI - [Sigmoid sinus thrombosis, a therapeutic problem]. AB - Thrombosis of the sigmoid sinus is a relatively uncommon illness. It may present in a septic or bland form, and the latter is more or less asymptomatic. Angiography, computerised tomography and magnetic resonance imaging are all at our disposal for diagnosis of both types of thrombosis, and proper diagnosis of the specific form of sinus thrombosis will determine the required therapy. Between 1985 and 1990 six patients with sigmoid sinus thrombosis were treated at the Departments of ENT, Johannes Gutenberg University, Mainz and Albert Ludwig University, Freiburg, Germany, on an in-patient basis. By means of these cases we present our experience with this uncommon condition. PMID- 8471101 TI - [Antibiotic treatment of Pseudomonas aeruginosa-induced ear canal disease]. PMID- 8471102 TI - Microbial reduction of aromatic carboxylic acids. AB - Several benzoic, cinnamic and phenylacetic acid derivatives were screened with 20 micro-organisms, mainly fungi, for the reduction of their carboxylic function. For all organisms several compounds were reduced in fairly good yields up to 80% to the corresponding alcohol. No general rule could be established, concerning the substitution pattern, as to which compounds were transformed to the alcohol. Generally the reactions were accomplished within 48-70 h. Only minor, if any, side products were detected. Dicarboxylic acids, such as phthalic or phenylglutaric acids and similar compounds could not be reduced by the microorganisms tested. PMID- 8471103 TI - Glycogen synthesis in rat liver from a pool of free glucose. AB - Glycogen synthesis in isolated perfused livers or livers of anesthesized rats (in situ), was studied using radioactively labelled fructose, lactate, and inositol as substrates. The specific radioactivity of glucose and glycogen was measured at various times and compared with that of some intermediates. The results suggest that liver glycogen is formed from the pool of free glucose which in turn is fed by the so-called "direct and indirect pathway" of glycogen synthesis. This points to an important role of glucose-6-phosphatase, an enzyme complex subject to regulation by glucocorticoids, well known promoters of hepatic glycogen synthesis. PMID- 8471104 TI - Classification of melanocytic lesions with color and texture analysis using digital image processing. AB - The incidence of malignant melanoma, the most dangerous skin cancer, has increased rapidly during the last decade, and the figures are still rising. Since well-trained and experienced dermatologists are able to reach only a diagnostic accuracy of about 75% in visual preoperative classification, the discriminating ability of digital image analysis was evaluated in more than 350 malignant melanoma and benign melanocytic lesions that had all been confirmed histologically. Color slides of melanocytic lesions were scanned and digitized. Computer algorithms were programmed in FORTRAN on a DECstation 5000/200. A feature set was calculated describing the texture, color and their distributions as well as asymmetry, size and border of each lesion. These features, together with the histologic diagnosis, were the input in a commercial statistical classification program. In contrast to the accuracy of 75% achievable by the human eye, a correct classification rate of about 92% was reached with the mathematical classifier as compared with the histologic diagnosis. PMID- 8471105 TI - Heterogeneity of DNA ploidy, proliferation index and nuclear size in human colorectal carcinomas. AB - Measurements of DNA ploidy, proliferation index and nuclear area were performed on 210 samples taken from 15 human colorectal tissues. The tissues were divided into four groups labeled G1, G2, G3 and C. For each of the 15 tissues 9 samples were taken from the so-called unaffected--i.e., marginal--mucosa (G1-G3 groups) and 5 from the tumor (C group). The 9 samples from the unaffected mucosa of each tumor were obtained at a distance of 10 cm (3 samples/tissue, G1 group), 5 cm (3 samples/tissue, G2 group) and 1 cm (3 samples/tissue, G3 group) from the tumor. Computerized cell image analysis was carried out on Feulgen-stained cell suspensions obtained from paraffin-embedded, formalin-fixed tissues. The results revealed that four to five analyses are necessary to detect minor aneuploid cell nuclei populations in human colorectal tumors. A definite homogeneous diploid pattern was found in the G1-G3 samples. In contrast, proliferative activity varied widely between the normal and tumor samples, with such variations observed at both the sample-to-sample and tissue-to-tissue level. The nuclear area also varied markedly across the samples from a given tissue--i.e., both marginal and tumoral and across the tissues themselves. Finally, we observed that the diploid tumors, the nuclear sizes of which varied as widely as those of the aneuploid tumors, possessed a higher proportion of highly proliferating samples than did the aneuploid. PMID- 8471106 TI - Discriminant analysis for classification of murine melanomas and human cervical epithelial cells. AB - Computer analysis of cell images offers many advantages over routine visual examination. It leads to quantitative and accurate detection of subvisual information and provides reproducible measures so that objective decisions in cancer diagnosis become possible. Such diagnostic decisions usually follow partly from a classification process. In this paper two multivariate discriminant analysis methods--namely, linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA)--are presented. LDA and QDA were used to classify cytologic data based on some morphodensitometric measurements. The cytologic data constituted two samples, one representing B16 cell lines and the other including three types of normal human cervical epithelial cells. LDA and QDA were assessed both individually and in comparison to each other, mainly on the basis of the rate of correct classification and robustness. The measurements extracted from the cytologic data employed were shown to be stable and consistent. The statistical results obtained from experiments on cervical cells look particularly promising and encouraging for future work. It has also been shown in this study that the classification techniques employed are valid and that LDA performed almost as well as QDA. PMID- 8471107 TI - Morphometric analysis of neoplastic renal aspirates and benign renal tissue. AB - This study was designed to develop a practical morphometric procedure for the diagnosis of carcinoma in renal aspirates. We studied aspirates from renal cell carcinomas (grades 1-2) and normal kidneys. Video images of nuclei were traced on a high-resolution, touch-sensitive screen connected to an image analysis system. From each tracing the computer calculated nuclear perimeter length, nuclear profile area, maximal chord length, and the means and standard deviation for all measurements. Size distribution of nuclear profile areas and perimeter length in discrete bins ranged, respectively, from 30 to 80 at 10 microns2 intervals for areas and from 1 to 12 microns at 1-micron intervals for the maximum chords. The size distribution plots for the maximal chord of individual nuclei demonstrated an early narrow peak at low values for normal renal aspirates (peak located in the class ranging from 7 to 8 microns), while a broader, flatter peak with a shift to the right and a malignant tail was seen in renal cell carcinoma aspirates (peak located at 9-10 microns). These data were used for multivariate analysis to form two categories to establish a data base against which unknown cases could be tested. Multivariate analysis using a total of 14 variables yielded a value of 169.1 for the euclidean distances between the center of clusters of the neoplastic and normal renal aspirates and confirmed the classification with posterior probabilities of 1.0. From these data, automated classificatory analysis of 10 unknown cases was performed by means of the k nearest neighbor procedure, with correct classification established in each case. PMID- 8471108 TI - Computer-designed expert systems for breast cytology diagnosis. AB - Three expert systems have been developed to diagnose from nine scalar values visually assigned to epithelial cells obtained by breast fine needle aspiration. These expert systems achieved up to 0.98 sensitivity and 0.97 specificity. When applied to 804 breast masses, the clinical sensitivity was 0.98 and specificity was 0.93 (exclusive of the 0.04 unsatisfactory aspirates). Cancers can be missed physically during the aspiration process; thus, some clinically suspicious masses were biopsied despite benign cytology. This contributed to the difference between the expert system and clinical specificities. PMID- 8471109 TI - Stress-related psychophysiological reactions of truck drivers in relation to anxiety, defense, and situational factors. AB - A system analytic frame of reference is chosen for analysing interindividual differences in driving a technically optimised tank-lorry in comparison to a standard tank-lorry. Seven professional tank-lorry drivers were tested with psychological tests, and their test results were related to physiological measures assessed under different driving conditions in both lorry types. Two dimensions were used to explain the pattern of interactions between the independent (psychological and situational) and dependent (physiological) variables. It is argued that beyond technical improvements, also taking into account information on personality variables and situational factors is a promising approach to accident prevention research. PMID- 8471110 TI - The call for help after an injury road accident. AB - How soon will the authorities receive a call for help after an injury road accident? In urban Missouri 70% of the calls were received in less than five minutes. But in rural Missouri only 34% of the calls came in that quickly. These figures are based on a merge of police and emergency medical services accident data in which the earlier of the two notifications is selected as the time of first call. Police estimates of accident time are used here to calculate the interval from accident to the first call. The police estimates lack precision. This is shown by the high percentage of rounded numbers. As averages, however, these estimates show little evidence of bias. In urban areas, delays are related to time of day and type of road system, while in rural areas, remoteness of location is an added factor. Difficulty in finding a telephone quickly in certain road environments can be a problem. However, installing more stationary telephones along roads may be inefficient. Large areas would have to be covered to insure even a modest reduction in delays. More thought, therefore, should be given to the use of innovative vehicle-to-satellite technologies. PMID- 8471111 TI - The duration of speed reductions attributable to radar detectors. AB - The duration of speed reductions attributable to radar detector use was observed. When the entire traffic stream was exposed to police radar, the proportion of vehicles traveling more than 10 mph over the speed limit dropped initially from 42% to 28%, but by one mile after exposure, this percentage had already increased to 38%. When speeding vehicles with radar detectors (about 45% of all speeding vehicles) were exposed to police radar, speeds dropped by approximately 15%, but by one mile after exposure, nearly half of the reduction was recovered. These findings indicate that radar detector users slow only briefly when alerted to police radar and that radar detectors are use primarily to avoid speed limit enforcement. PMID- 8471112 TI - Harmful events in crashes. AB - This study examined objects struck in motor vehicle crashes which cause injury or property damage--called harmful events on national accident data files. The percentage of loss due to fatalities was found to differ greatly by harmful event type. Comprehensive costs were used to combine data on fatalities, injuries, and property damage only (PDO) vehicles into a single economic measure of crash loss. Use of comprehensive costs can reduce distortions that may occur in analyses limited to fatal events. Large differences were identified in average injury costs by harmful event type, indicating the need to use specific harmful event injury costs in analyses whenever possible. Major differences found between first and most harmful events in ran-off-road crashes indicate a need for states to collect both data elements on their police accident report forms. PMID- 8471113 TI - Restrained occupants on the nonstruck side in lateral collisions. AB - Of injury-producing collisions with high seat belt use, some 25% to 30% are lateral collisions. This paper describes some of the characteristics of those collisions as they relate to the front-seat occupant sitting on the side opposite to the impact. The data came from a stratified sample of in-depth crash investigations conducted in the Birmingham region in the period 1983 to 1989 involving current model cars. Crash severity was assessed using the Vehicle Deformation Index (VDI) of the Collision Deformation Classification (CDC) ratings and velocity change. Injury severity was assessed using AIS 85 for each body region. 193 cases of restrained occupants in nonstruck side collisions were examined. Of those occupants with head injuries of AIS < or = 2, 35% came out of the shoulder section of the seat belt. Of abdominal injuries of AIS < or = 2, 72% came from the seat belt itself. Interaction between front seat occupants was not a frequent cause of injury to the nonstruck side occupant. Some aspects of seat belt geometry might be changed so that the trajectory and loading of the nonstruck side occupant are improved. PMID- 8471114 TI - Needle covers reduce needlestick injury. AB - The objective of the study, conducted in the general wards of Flinders Medical Center in South Australia, was to determine whether the risk of needlestick injuries from hypodermic needles could be reduced by the use of needle covers that are applied with a one-handed technique immediately after use of the needle. Baseline rates of needlestick injury were collected for a year prior to the use of needle covers, and incident cases of needlestick injury were collected after needle covers were introduced. The odds ratio, derived from pre- and post intervention data, for injuries over which the use of needle covers could have had no influence, was used to show that the net effect of other influences on needlestick rates was not significant. The use of needle covers was associated with a significant reduction in needlestick injuries to nurses. The odds ratio for needlestick injury for nurse injuries that needle covers could not have prevented was 0.92. (95% CI 0.40-2.03). The odds ratio for needlestick injury for nurse injuries that needle covers could have prevented was 0.40 (95% CI 0.18 0.82). Although the odds of ratio for needlestick injury to cleaners was 0.19, the 95% exact confidence interval was 0.00-1.64. PMID- 8471115 TI - Single-vehicle crashes and alcohol: a retrospective study of passenger car fatalities in northern Sweden. AB - This retrospective study of fatal passenger car crash victims in northern Sweden compares 396 multiple-vehicle (MV) and 201 single-vehicle (SV) fatalities from 1980 through 1989. Compared to MV fatalities, SV victims were more frequently males, were younger, were more often inebriated, had higher blood alcohol concentrations, had a higher frequency of fatty liver, and were less often restrained. The SV fatalities occurred most often from May through October, from Fridays through Sundays, and from 9 p.m. to 6 a.m. The road surface was usually dry, especially for drunken SV drivers. The SV drivers also more often lacked a valid driver's license. The study confirms that alcohol is one of the most important factors associated with traffic fatalities, particularly in SV crashes. More than half (56%) of the SV victims were inebriated by alcohol (MV, 11%), had a mean blood alcohol concentration of 1.9 g/l (MV, 1.6 g/l), and one-third had a fatty liver (MV, 20%). We also found a relation between fatty liver and increased blood alcohol concentrations, suggesting that studies regarding the role of alcohol in traffic fatalities should also include an evaluation of liver morphology. PMID- 8471116 TI - Elderly in the traffic environment: analysis of fatal crashes in northern Sweden. AB - Fatal crashes of the elderly (> or = 60 years; N = 379) in northern Sweden in the traffic environment, between 1977 and 1986, were investigated using autopsy and police reports. Males had double the death rate of females. The car occupants made up the largest category (43%) followed by pedestrians, pedalcyclists, and two-wheel-motorvehicle (TWMV) riders, but the risk of fatal injury per unit distance travelled was highest for pedestrians and pedalcyclists. Most car occupants were killed in vehicle-vehicle crashes, mostly in the daylight and at intersections or straight roads. Ice and/or snow (31%) was the major precrash factor. In two-thirds of single car crashes, roadside hazards such as trees were involved. Most elderly fatally injured car drivers were responsible for the crash, and they were commonly involved in collisions with oncoming vehicles. Only 4% of the fatally injured car drivers were driving under the influence of alcohol. Head injuries appeared to be more common in side impact than in frontal impacts. Serious chest injuries were more common than head injuries in car crashes. One-quarter of the pedestrians were injured at pedestrian crossings and about half during darkness. One in six pedestrians were under the influence of alcohol. All pedalcyclists were injured in collisions with motor vehicles and most were injured at intersections. Pedestrians, pedalcyclists, and TWMV riders had more serious head injuries than chest injuries. PMID- 8471117 TI - The effectiveness of seat belt legislation in reducing various driver-involved injury rates in California. AB - This study makes use of econometric models to examine the impact of seat belt laws on various driver-involved injury rates in California in both single- and multiple-vehicle accidents. The study makes use of a large data set from the U.S. D.O.T. State Traffic Accident Files and accounts for the general impact of seat belt laws as well as their dynamic effects on injury rates. The models adjust for a wide range of additional contributing factors to injury rates, including the influence of unemployment rates, speed limits, companion effects, and others. Robust results are obtained for the efficacy of seat belt legislation on reducing (moderate to fatal) injury rates in California. PMID- 8471118 TI - Life-threatening and disabling injuries in car-to-car side impacts--implications for development of protective systems. AB - Improvements to the passive safety of cars in lateral collisions are of great importance. This study of injuries in car side collisions in Sweden by the use of two evaluation methods has been performed to establish the basis for future development of protective systems for this type of accident. The Folksam car accident data file has been used. Injuries were found to be twice as common for near-side than for far-side* occupants in car to car impacts. Serious to fatal (AIS 3-6) injuries to belted front seat occupants in near side impacts (10% of all injuries) were compared with the estimated number of injuries to different parts of the body with risk of serious consequences (RSC)--either deaths or permanent disabilities (4.5% of all injuries). The two injury evaluation methods resulted in different ranking orders. AIS 3-6 injuries were received by the chest (37%), abdomen/pelvis (25%), and the head (15%). The RSC method gave a ranking order of head (25%), neck (21%), leg (15%), chest (14%), and abdomen/pelvis (11%). The method of evaluating AIS 3-6 injuries emphasizes only the threat to life. The RSC method also takes into account the risk of disabilities. Injuries to the neck and the leg were found to be most disabling, whilst the injuries to the head, chest, and abdomen/pelvis were the most life threatening. The study also shows that elderly people receive significantly more chest injuries (relative to the number of head injuries), on average four times more than young people.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471119 TI - The role of exposure in comparisons of crash risk among different drivers and driving environments. AB - Crash rates based on drivers, driver-kilometers, and driver-days in the denominator were compared, using survey estimates of time and distance driven and the annual frequency of traffic crashes in Ontario. Rates by age, sex, and region were computed for all crashes and for crashes resulting in injury or fatality. Young male drivers remained at high risk for all types of denominator; older women had high rates when distance was included in the denominator. When time spent driving was substituted, men and women drivers over 60 had very similar rates. For comparisons of rural residents with urban and northern residents, time and distance give equivalent results. These findings suggest that apparent differences in crash risk per kilometre, whether for older women or for urban drivers, is explained by differences in typical driving speed and environment. Exposure time is better than distance to explain crash risk among drivers and regions with very different driving patterns and environments. PMID- 8471120 TI - Mass ratio and relative driver fatality risk in two-vehicle crashes. AB - The relative risk, R, of a driver fatality in the lighter of two cars compared to the risk in the heavier is determined as a function of the ratio, mu, of the mass of the heavier to that of the lighter, using Fatal Accident Reporting System data for 1975-1989. In all of many cases investigated, the data fitted well the functional relationship R = A mu u. When the cars differ only in mass, A = 1; if they differ in another dichotomous characteristic, such as old compared to new model years, A estimates the influence of this other characteristic when the masses are equal. The results show that if a driver transfers to a car lighter by 1%, that driver's fatality risk in a two-car crash compared to the risk to the other involved driver increases by between 2.7% and 4.3%, the specific value depending on other factors, such as model year. When one car crashes head-on into the side of another of equal mass, driver fatality risk in the side-impacted car compared to that in the frontally impacted car is 4.5 +/- 0.6 times as great for right-side impacts and 10.1 +/- 1.7 times as great for left-side impacts. Extending the analysis to vehicles other than cars provides empirical evidence that two previously stated "laws" apply systematically over a wide spectrum of vehicles, from mopeds, through motorcycles, small cars, large cars, small trucks to large trucks. These laws are that, when other factors are equal, (1) the lighter the vehicle, the less risk to other road users, and (2) the heavier the vehicle, the less risk to its occupants. PMID- 8471121 TI - An emergency rescue service in Brazil. PMID- 8471122 TI - Studies of catecholamine metabolism in schizophrenia/psychosis--II. AB - Acutely psychotic schizophrenic patients were maintained on debrisoquin (DBQ) throughout 5 weeks of treatment with haloperidol. Treatment with haloperidol caused initial increases in urinary homovanillic acid (HVA) output that returned toward baseline by the 5th week. During haloperidol treatment, plasma levels of HVA tended to decrease, concurrent with increased renal clearance of HVA. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and urinary MHPG output both decreased over the course of treatment. The differences in HVA and MHPG metabolism suggest differential effects of treatment on dopamine and norepinephrine systems. Neuroleptic treatment also abolished the marked morning decreases in plasma HVA concentrations (reported in part I). PMID- 8471123 TI - The 5-HT3 receptor in mammalian brain: a new target for the development of psychotropic drugs? PMID- 8471124 TI - Schizophrenia: dopamine D1 receptor sequence is normal, but has DNA polymorphisms. AB - Genes that regulate dopamine (DA) receptors may underlie the overactive DA system in schizophrenia. Since it is known that there is an abnormally reduced or absent regulation of the DA D2 receptor by the DA D1 receptor in the postmortem schizophrenia brain, the human DA D1 receptor gene was sequenced from genomic deoxyribonucleic acid (DNA) of seven schizophrenic individuals. The tissues from two schizophrenics had previously been found to have a reduced link between DA D1 and D2 receptors. The D1 receptor genes were amplified by the polymerase chain reaction, subcloned, and sequenced. Although three DNA polymorphisms were found, the deduced amino acid sequence of the DA D1 receptor was normal in these tissues. PMID- 8471125 TI - Schizophrenia: normal sequence in the dopamine D2 receptor region that couples to G-proteins. DNA polymorphisms in D2. AB - Because dopamine (DA) D2 receptors are a target in neuroleptic therapy and have been found to be elevated in schizophrenia, the human DA D2 receptor gene was examined for possible abnormalities in schizophrenia. Moreover, since D2 receptors in psychosis have a reduced coupling to D1 receptors, the cytoplasmic third loop of D2 was chosen for deoxyribonucleic acid (DNA) sequencing, since this region is essential for coupling to G-proteins. This region also contains exon 5, which is expressed in the long form of D2, but not in the short form of D2. In eight schizophrenia cases, this region had normal exon sequences (exons 4, 5 and 6), and normal sequences at its intron-exon junctions. However, exon 6 contained three DNA polymorphic base changes, and introns 4 and 5 revealed three missing bases and two polymorphic base changes, none of which would be expected to alter the D2 receptor protein in schizophrenia. PMID- 8471126 TI - Electroencephalographic sleep in recently remitted, elderly depressed patients in double-blind placebo-maintenance therapy. AB - The aim of this double-blind placebo-controlled study was to assess the effects of clinical state on electroencephalographic (EEG) sleep measures in elderly patients with recurrent major depression. We hypothesized that rapid-eye movement (REM) latency and delta sleep ratio would remain stable between actively depressed and remitted states (i.e., show state independence), and measures of sleep continuity would improve with remission (i.e., show state dependence). Fifteen elderly outpatients (mean age 65.3 years) had sleep evaluations while ill and after remission, an average of 38 weeks later. All patients were in a double blind placebo-maintenance condition at the time of follow-up studies. The major findings were: 1) no significant change in either REM latency or delta sleep ratio; 2) reduction in early morning awakening; and 3) improvement in subjective sleep quality despite the stability of most polysomnographic measures. We conclude that REM latency and delta sleep ratio are state-independent in patients with late-life depression, and that early morning awakening and sleep quality improve with remission of symptoms. These findings suggest that EEG sleep changes may have significance for understanding the longitudinal course of depression in late life. PMID- 8471127 TI - A multicenter study of the light visor for seasonal affective disorder: no difference in efficacy found between two different intensities. AB - Fifty-five patients with winter seasonal affective disorder (SAD) were treated with a light visor, a newly developed portable light-delivery system, in a controlled parallel design. A dim (400 lux) visor was compared with a bright (6000 lux) visor for either 30 or 60 minutes in the morning for 1 week. Response rates for these two treatments were 36% and 56%, respectively; the duration of treatment sessions did not affect outcome. There was no evidence that the brighter visor was superior in efficacy to the dimmer one. Significantly greater relapse occurred following withdrawal of the dimmer visor. Alternative explanations for these findings are that the light visor is acting as a placebo or that it is equally effective over a wide range of intensities. PMID- 8471128 TI - Effects of acute and chronic alprazolam treatment on cerebral blood flow, memory, sedation, and plasma catecholamines. AB - The effects of 0.014 mg/kg intravenous alprazolam administration on cerebral blood flow (CBF), memory, sedation, and plasma norepinephrine and epinephrine were determined in eight healthy males at baseline levels and following 1 week of daily oral alprazolam treatment. At baseline, intravenous alprazolam administration caused acute reductions in whole-brain CBF (25% to 30% decrease), memory, plasma epinephrine, and self-rated alertness. Following 1 week of alprazolam treatment, tolerance developed to the acute effects of intravenous alprazolam on CBF, memory, and plasma epinephrine. There were no consistent regional neuroanatomic differences in the CBF effects of acute alprazolam, or in the development of tolerance to these effects, and no correlations between the various measures of acute alprazolam effects on either test day. PMID- 8471129 TI - Psychological effects of MDE in normal subjects. Are entactogens a new class of psychoactive agents? AB - The so-called entactogens 3,4-methylenedioxymethamphetamine ([MDMA] also known as "Ecstasy," or "Adam") and its analog 3,4-methylenedioxyethamphetamine ([MDE] also known as "Eve") exert similar psychotropic effects in humans. Two double-blind placebo-controlled psychometric studies with normal control subjects were conducted. Placebo or MDE (140 mg) was administered orally to eight male volunteers at 1:30 P.M. and to six subjects (3 male, 3 female) at 11 P.M. Psychologic tests and clinical ratings were performed 1 hour before the administration of the drugs, as well as 2, 5, and 24 hours after drug intake and 7 days thereafter in the first study. In the second study, measures were taken at times -1, +8.5, +24 hours, and +7 days. The majority of the psychotropic effects resembled those that have already been described in anecdotal reports. The substance produced a partially controllable state of enhanced insight, empathy, and peaceful feelings. All subjects displayed a general stimulation with increased psychomotor drive, logorrhea, and facilitation of communication. One of the fourteen volunteers developed a toxic psychosis. One volunteer displayed a dysphoric reaction, one suffered from episodes of anxiety for some days after the experiment. The findings support the hypothesis that MDMA and MDE represent a novel pharmacologic class. PMID- 8471130 TI - Suicidal behavior and psychotropic medication. Accepted as a consensus statement by the ACNP Council, March 2, 1992. PMID- 8471131 TI - On the value of measuring dopamine, norepinephrine and their metabolites in schizophrenia. PMID- 8471132 TI - Studies of catecholamine metabolism in schizophrenia/psychosis--I. AB - Acutely psychotic schizophrenic patients not taking antipsychotic medications and control subjects were studied before and during treatment with debrisoquin (DBQ), an inhibitor of monoamine oxidase, which does not penetrate into brain. Homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in plasma, urine, and cerebrospinal fluid (CSF). Significant differences between patients and control subjects were more easily discerned during treatment with DBQ. In patients, HVA was increased in plasma but not in urine or CSF, although MHPG was increased in all three fluids. There were many significant correlations between plasma MHPG and HVA levels and clinical ratings of psychoticism. Plasma MHPG correlated positively with both the severity of positive and negative symptoms and plasma HVA correlated only with positive symptom severity. These data suggest that both dopamine and norepinephrine (NE) metabolism are disturbed in acutely psychotic schizophrenic patients; disturbed NE metabolism may relate to negative symptoms as well. PMID- 8471133 TI - Critical evaluation of the clinical relevance of the IgG subclasses assays. AB - Human IgG subclasses play a major role in the physiological regulation and functions of the immune system. There "personality" is obvious. However, the determination requires appropriate reagents and technology. For the IgG1, IgG2, IgG3 subclasses, the radial immunodiffusion technique may be sufficient. For the IgG4 subclass determination and measurement, more elaborate techniques are required. These measurements of existing proteins are of major interest in congenital as well as acquired immune deficiencies more often, besides the total subclass deficiency, these are of utmost interest to evaluate the specific response of a given subclass to a specific antigen. The IgG4 allergen specific subclass has been considered to be involved both in allergic reactions and associated with the appropriate response to allergen-specific immunotherapy. It is now accepted that IgG4 does not play an discernable role in the acute inflammatory response of type I hypersensitivity; it has also been demonstrated that a number of patients who demonstrate elevated levels of allergens specific IgG4 are not protected against allergenic exposure, and conversely, a number of patients who have been heated by immunotherapy without demonstrating any significant increase in their serum levels of allergen specific IgG4 are indeed very well protected. In the field of allergy, the IgG4 determinations remain a matter of controversy and research. PMID- 8471134 TI - Immunological study of vulvar lichen sclerosus: preliminary considerations. AB - Sclero-atrophic lichen (LSA) is a dermatosis that is well defined from the clinical and histological viewpoints, but the etiology remains unknown. The main symptom is a permanent pruritus which results in a gynecological consultation. We have studied the immunological status of 48 patients with LSA and 33 controls. The LSA patients showed a significant diminution of peripheral CD3 and CD1 and tissue CD2, CD3, CD1 and CD8. There was no difference of IgG, IgM or tissue C3c, or serum C3c and C4. These patients also had a higher incidence of autoantibodies. PMID- 8471135 TI - Mycobacterial infection in HIV+ patients detected with a new immunological method (TB test). AB - Antibody response to antigen A60 (a mycobacterial antigen) was evaluated in ELISA in 18 HIV+ subjects with clinical and cultural evidences of mycobacterial infections, in 10 HIV+ subjects without Mycobacterial infections and in 22 healthy donors. We found higher levels of specific IgG in the HIV+ patients with Mycobacterial infections (mean 179.2 +/- 83 U) compared to the values of the donors (mean 92.5 +/- 35.5 U: p < 0.01). This test may be useful in the diagnosis of tuberculosis, but it needs clinical validation. PMID- 8471136 TI - [The effect of respiratory rehabilitation on the functional ventilation changes in the asthmatic child]. AB - The aim of this study was to evaluate the improvement of lung function abnormalities during asymptomatic periods in children with perennial atopic asthma after physical respiratory rehabilitation and swimming (RR). MATERIAL AND METHODS: 240 lung function tests were performed regularly by whole-body plethysmography during asymptomatic periods on 68 atopic asthmatic children aged 5-13 (means 8.7 y), in a follow up four years study (1983-87). TLC, VC, FEV1, Raw, MEF50, RV and TGV were recorded. We selected TGV for measured hyperinflation, Resistance (Raw) for bronchial obstruction and MEF50 for small airways obstruction. We divided these children population in two groups: group A control (20 subjects, means 9.3 y. age) immunotherapy (IT) alone; group B (48 subjects, means 8.03 y. age) IT and respiratory rehabilitation and swimming. Furthermore, we compared the evolution of the lung function according to the severity of asthma on B group alone. RESULTS: the number of hyperinflated or bronchial obstructed children who did RRS is significantly smaller than on the control group. Nevertheless, breathing exercises and swimming has no effect on peripheral airway obstruction. When we compared the effect of asthma on B group alone, we noted that the recovery of lung abnormalities were observed on the great majority of mild and moderate hyperinflated and bronchial obstructed asthma. In severe asthma, the results were not so good, particularly on bronchial and peripheral airway obstruction. In these last cases the functional prognosis will be uncertain. CONCLUSION: respiratory rehabilitation and swimming have an unquestionable effect on improvement of hyperinflated asthmatic children, some effect on improvement on permanent bronchial obstruction, and without any benefit on permanent peripheral airway obstruction. Lung function tests might be monitored the RR in all asthmatic children with lung function impairment. PMID- 8471138 TI - [Information on AIDS in companies]. PMID- 8471137 TI - In vitro effects of an immunoglobulin preparation for intravenous use (IVIG) on T cells activation. AB - The "in vitro" effect of different concentrations of polyclonal human immunoglobulins for intravenous use (IVIG) on cultured T-lymphocyte response to phytohemagglutinin (PHA) was evaluated. Four dilutions of IVIG corresponding with the "in vitro" doses currently employed in therapy have been tested by the effect on PHA stimulated cultures. The dilution of IVIG corresponding with a low therapeutical dose gives a higher statistically significant stimulating effect. The results obtained in our work agree with previous studies performed on activated B-cells. We can suppose the immunoglobulins may control the T lymphocyte activation either by a direct link with a specific Fc-receptor expressed on the surface of activated T-cell or by affecting the cytokines release from monocyte cells. PMID- 8471139 TI - Adhesion molecules in immunity and inflammation. AB - Adhesion molecules are essential components of immunitary response and inflammation. Adhesion molecules could be classified as integrins, selectins, immunoglobulins superfamily and carbohydrates. The role of adhesion molecules in inflammation, immunity cancer, acute respiratory diseases, transplantation and his possible relevance in therapy are reviewed and discussed. PMID- 8471140 TI - Burn victims after a major disaster: reactions of patients and their care-givers. AB - There have been considerable advances in the physical management of burns, and there is a greater awareness of their psychological impact. However, much less attention has been given to the staff who have to deal with burn victims. Disasters are critical incidents which offer a magnified opportunity to appreciate with what care-givers have to cope and how they do so. This paper identifies how complex are the psychological and emotional reactions associated with burn care, and it advocates that more should be done, by means of debriefing, to cater for the needs of staff after critical incidents. PMID- 8471141 TI - Catecholamines: important factors in the increase of oxidative phosphorylation coupling in rat-liver mitochondria during the early phase of burn injury. AB - Thirty minutes after Sprague-Dawley rats had been injected subcutaneously with epinephrine or norepinephrine, the respiratory control ratio (RCR), the rate of O2 consumption in state 3 and the rate of ATP formation in liver mitochondria succinate respiratory chain were increased. The rate of O2 consumption in state 4 was increased or only slightly increased. When the rats were injected with the adrenergic blocking agents, timolol or phenoxybenzamine, 1 h before the burn, the activities of the succinate respiratory chain was partly inhibited 30 min postburn. Compared with our previous results, it can be suggested that catecholamines may play an important role in the increase of oxidative phosphorylation coupling in the early phase of burn injury. PMID- 8471142 TI - Side effects of laser therapy, modified by ultraviolet irradiation and para aminobenzoic acid in mice. AB - Scarring is a well-known side-effect of cutaneous laser treatment and exposure to solar ultraviolet radiation is suspected to increase scar formation. We investigated how wounds and scarring were modified by interfering in the laser induced inflammation using ultraviolet radiation and para-aminobenzoic acid. A copper vapour laser operating at 578 nm was used at three different intensities and doses. The ultraviolet radiation was administered three times weekly prior to and four times weekly after the laser treatment. The daily dose was 21.5 kJ/m2 equivalent to 3.5 Basic-MED. The laser-induced wounds were evaluated daily and histological and biochemical analyses were used to estimate scarring. Ultraviolet irradiation resulted at some of the used laser intensities in decreased scores of maximum wound area, wound healing time, cumulated wound area, and a decreased skin content of hydroxyproline, whereas the degree of the chronic fibrosis tended to increase. Application of para-aminobenzoic acid before the solar ultraviolet irradiation did not change the acute wound scores but reduced, although not significantly, the degree of fibrosis. PMID- 8471143 TI - A recombined skin composed of human keratinocytes cultured on cell-free pig dermis. AB - Treatment of full skin thickness burns requires replacement of both the dermal and the epidermal components of the skin. We describe a method of preparing recombined human/pig skin (RHPS) by cultivating human keratinocytes on dried cell free pig dermis (CFPD). CFPD dried on a tissue culture dish forms a thin collagen film which behaves like a firm substrate for cell cultures. HK were grown on the epidermal side of the CFPD using lethally irradiated 3T3 cells as feeders. After reaching confluency of human keratinocytes, human fibroblasts can be cultured on the dermal side of the RHPS. It was possible to obtain approximately 500 cm2 of the RHPS from 1 cm2 human split-skin graft in 3 weeks. RHPS is easy to handle, is similar in structural, mechanical and adhesive properties to the normal skin, and can be meshed. This RHPS might be advantageous for permanent covering of wounds in major burns. PMID- 8471144 TI - Plasma tumour necrosis factor-alpha (TNF-alpha) levels in patients with burns. AB - Levels of plasma tumour necrosis factor-alpha (TNF-alpha) were determined consecutively in 42 patients with burns > 20 per cent of the total body surface area using an enzyme-linked immunosorbent assay. In the early period after injury (including the period of burn shock), 24 patients had detectable TNF-alpha levels in their plasma. However, the plasma TNF-alpha levels at the time of admission were very low and did not correlate with the extent of the burn or the prognosis. In contrast, the maximum plasma TNF-alpha level over the whole clinical course was significantly correlated with the area of the burn and the prognosis. No correlation was found between the plasma TNF-alpha and plasma endotoxin levels. TNF-alpha may be produced locally in infected burns and monitoring of plasma TNF alpha levels may be a useful prognostic indicator for burns patients. PMID- 8471145 TI - Management of partial thickness burns with Granuflex 'E' dressings. AB - In a prospective, open, randomized and parallel group trial, 98 patients with partial thickness burns suitable for outpatient management were treated with either Granuflex 'E' (n = 49) or Bactigras (n = 49). The objective was to compare the safety, efficacy and performance characteristics of Granuflex 'E' with Bactigras. The overall rating of the dressing by the investigators and the patients showed a significant preference for Granuflex 'E'. In addition, the quality of healing was rated as 'excellent' in 56 per cent of patients treated with Granuflex 'E', compared with only 11 per cent in the group treated with the conventional dressing. Granuflex 'E' is safe, effective and flexible and we recommend that it should be used as the first-choice dressing in the management of partial skin thickness burns. PMID- 8471146 TI - Expanding oral plastic splint for burn patients. AB - An expanding oral plastic splint for preventing microstomia from deep facial burns is described. This splint adjusts to suit the affected oral angles without the need for taking any impression before fabrication. It is especially suitable for severely injured patients starting from the early period shortly after injury, even if the patient has been intubated. Furthermore the expansion forces can be controlled easily according to the degree of contracture. PMID- 8471147 TI - The estimation of blood loss during burns surgery. AB - The estimations of blood loss and transfusion requirements during burns surgery are notoriously difficult. This clinical study investigated the effectiveness of estimates made by junior and senior burns surgeons and senior anaesthetists by comparing them with calculated blood losses. Regression analysis shows good correlation between these methods (r-value range 0.75-0.97), although 'eye balling' the losses tends to underestimate the transfusion requirements (regression slope coefficients ranged between 0.56 and 0.87). In only five out of 46 procedures was there a need for late transfusion for an unacceptably low haemoglobin level (< 10 g/dl). This provides further empirical evidence for the clinical value of each member of the team voicing an estimate of the loss at the end of the procedure. The mean blood loss for 1 per cent of burn excised or split skin donor site harvested was 117 ml in adult cases. Blood loss can also be expressed as a mean percentage of the patient's calculated total blood volume for each 1 per cent burn excised or autograft harvested, giving figures of 2.6 per cent for adults and 3.4 per cent for children. Gravimetric analysis of soiled swabs underestimates the blood loss by approximately 50 per cent. PMID- 8471148 TI - Chronically exposed calvarium following electrical burns. AB - Electrical burns of the scalp and calvarium are uncommon, but due to various conditions peculiar to India such injuries are seen frequently. The presentation of such patients at hospital is late because of the paucity of specialized care facilities and understanding of the disease process. Such injuries usually cause necrosis of the scalp and underlying calvarium with sequestered bone being retained in situ by the flimsy adhesions of underlying granulation tissue and overhanging edges of the scalp all around caused by secondary wound contraction. This paper gives our experience of 14 such cases, explaining the reasons for the chronic state and their subsequent clinical management. PMID- 8471149 TI - Widely expanded postage stamp skin grafts using a modified Meek technique in combination with an allograft overlay. AB - A method for obtaining widely expanded postage stamp autografts, first described in 1963 by C.P. Meek, has been evaluated in our burns unit. The technique, in which an expansion ratio of 1:9 is achieved with the aid of special prefolded gauzes, was combined with an overlay of glycerol-preserved allografts applied 1 week after grafting. This delay did not appear to affect graft take. In a series of 16 consecutive skin graft procedures performed on 10 patients with extensive burns, the mean epithelialization rate was 90 per cent (range 70-100 per cent) within 5 weeks. Cosmetic results were comparable to those achieved with widely expanded mesh grafts. The Meek technique utilizes small pieces of autograft, and has proved to be a practical alternative to mesh grafts when donor sites are limited. PMID- 8471150 TI - Estimation of the calorie requirements of burned Chinese adults. AB - Studies of energy expenditure in 75 adult Chinese patients with burns covering between 5 and 98 per cent of the total body surface area (TBSA) gave the following formula for an optimal nutritional regimen: the daily calorie input should be 1000 x m2 (surface area) + 25 x per cent TBSA. Glucose should provide between 55 and 60 per cent of the calories, fat between 20 and 30 per cent, and protein between 15 and 20 per cent. The calorie to nitrogen ratio should lie between 150 and 170 to 1. PMID- 8471151 TI - Burns complicated with gastrointestinal haemorrhage--an analysis of 70 cases. AB - Clinical data concerning the age, burn surface area and depth, burn shock, the time and location of haemorrhage, amount of blood lost and prognosis are described in 70 burn patients who developed gastrointestinal haemorrhage. The relevant morbidity, diagnosis and treatment is discussed. PMID- 8471152 TI - Prehospital care of burns: an analysis of 3 years use of the emergency physician system (EPS) Cologne. AB - Little information is available about the vital parameters of burns victims shortly after the accident. Therefore cases of burns, electrical and caustic injuries presenting to the Cologne Emergency Physician System over 3 years (n = 262) were prospectively studied and analysed. The average incidence in Cologne, Germany (population 1 million), of burns victims attended by the Emergency Medical System and emergency physicians at the scene was 74 adults and 14 children per year. Children are mainly injured by scalds (41.4 per cent); adults by fire accidents (43 per cent). A classification of the victims at the site of the accident according to their vital signs (Trauma Score (TS) after Champion H. R., Sacco W. J. and Carnazzo A. J. et al. (1981) Trauma Score. Crit. Care Med. 9, 672) showed, that in spite of a major burn injury, the vital signs were usually not or only slightly impaired. Subsequent measurements instituted by the emergency physician at the scene increased with decreasing initial TS. With TS = 14, 50 per cent of the patients were intubated; below 14 points nearly 100 per cent. The fluid administered also increased with a decreasing TS. PMID- 8471153 TI - New advances in automatic disposable rotating cartridge skin staplers. AB - This report describes the design, operation, and mechanical performance of Auto Suture Multifire Premium disposable skin staplers and staples in a biomechanical laboratory investigation and a clinical evaluation. The performance of this reloadable stapler has been compared with that of a new disposable skin stapler with a rotating cartridge, the Proximate RH stapler. The latter exemplifies a disposable skin stapler whose cartridge cannot be reloaded. The Auto Suture Multifire Premium disposable skin stapler has been designed so that its cartridge can be reloaded during a single surgical procedure. The most obvious advantage of this new device is that it substantially reduces the cost of skin stapling during surgery. Another unique benefit of this stapler is that it can accommodate either regular or wide staples, allowing the surgeon to use both size of staples without discarding the stapler. On the basis of this investigation, the Auto Suture Multifire Premium disposable skin stapler is recommended for skin incision and graft closure, since it provides maximal visualization of the wound as well as the staple during its formation. It delivers the staple into the skin or skin graft so that the topspan of the staple is above the skin or wound surface. In addition, the Auto Suture Multifire Premium disposable skin stapler has a prepositioning (precocking mechanism) that is controlled by the surgeon with minimal force, a mechanism which allows the stapler to hold its staple securely, even when its pointed legs extend beyond the delivery end of the stapler. The force required to form its staples is so low that the surgeon can staple repetitively without fatigue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471154 TI - Burns with pregnancy--a review of 25 cases. AB - We have treated 25 pregnant patients with burns over a period of 6 years (1986 91). During this period total admissions to the burn unit were 1260. There were 187 women of child-bearing age, with burns ranging between 15 and 100 per cent TBSA. We would like to emphasize that, with proper care, the prognosis of patients with burns who are pregnant is encouraging and is comparable to any other routine burn patient. Abortion was common in the first trimester of pregnancy. Septicaemia was the commonest cause of abortion. Fetal death is not always preceded by maternal death. PMID- 8471155 TI - Versatility of the free or pedicled superficial cervical artery skin flaps in head and neck burns. AB - The usefulness of the free or pedicled superficial cervical artery skin flap in reconstructive surgery of head and neck burns is reported. This flap can be made with the pivot point near the cervical region. Moreover, it can be elevated as a free or long vascular pedicled flap. Therefore, it is widely applicable in reconstructing the scar contractures of the head and neck, particularly in extensively and deeply burned patients. PMID- 8471156 TI - Osteomyelitis of the spine in a burn patient due to Candida albicans. AB - A 38-year-old white-skinned male was burned in an ultralight plane crash and sustained a 59 per cent body surface area burn, mostly full thickness skin loss. A fracture of the first lumbar vertebra was noted at admission which was treated without surgery. Candida septicaemia was diagnosed and treated during the acute phase of injury. Extensive grafting was required. Following discharge, the patient began experiencing low-grade back pain which was aggravated on postburn day 277 by a fall down a flight of stairs. Spinal radiographs obtained following this fall revealed osteomyelitis at the level of the eighth and ninth vertebrae with an intervertebral abscess. Following evacuation of the disc space during surgery, the organism was identified as Candida albicans. Treatment with amphotericin B and later fluconazole was initiated. Recovery was uneventful. The infection, probably of a haematogenous origin, is the first such case reported in the literature to our knowledge. PMID- 8471157 TI - Improvement of human keratinocyte isolation and culture using thermolysin. AB - We propose a modification of the conventional keratinocyte isolation method which has shown a significant improvement in the purity, colony forming efficiency (c.f.e.) and growth capacity of the isolated epidermal cell population. This method utilized thermolysin since it selectively digests the dermo-epidermal junction. Following separation from the dermis, the epidermis was digested with trypsin to obtain a single cell suspension. Compared with the conventional procedure, this isolation method was shorter and resulted in (i) cells displaying a higher colony forming efficiency, (ii) cells reaching confluence 1-3 days earlier, (iii) cells not contaminated by fibroblasts, (iv) a cell population containing all the basal layer keratinocytes. These cells were suitable for the establishment of primary cultures and could be subcultured. Such cell populations should be advantageous in studies of epithelial-mesenchymal interactions in which keratinocyte populations, free of fibroblasts, are desirable. In the treatment of extensively burned patients using cultured epidermal sheets, the main problem remains the time required for their production. Thus, the absence of fibroblast overgrowth of the keratinocyte cultures and the significantly reduced time to obtain confluent cultures and epidermal sheets with our method have very important implications for the treatment of large burn wounds. PMID- 8471158 TI - Bioactivation of halogenated hydrocarbons by cytochrome P4502E1. AB - Numerous halogenated hydrocarbons of the alkane, alkene, and alkyne classes are metabolized by P450 enzymes to products that elicit cytotoxic and/or carcinogenic effects. Such halogenated hydrocarbons include anesthetics (e.g., halothane and enflurane) and industrial solvents (e.g., carbon tetrachloride, chloroform, and vinylidine chloride). Formation of reaction intermediates from these compounds occurs via P450-promoted dehalogenation, reduction, or reductive oxygenation, with certain hydrocarbons undergoing all three reaction types. Of the multiple forms of P450 present in liver microsomes, P4502E1 has been identified as the primary catalyst of hydrocarbon bioactivation in animals and, most likely, in humans as well. As hepatic concentrations of this P450 enzyme are highly inducible by ethanol and similar agents, prior exposure to 2E1-inducing compounds can play a pivotal role in halogenated hydrocarbon toxicity. Considering that metabolism governs the cytotoxicity and carcinogenicity of halogenated hydrocarbons, an understanding of the mechanism(s) underlying 2E1 induction in man becomes all the more important. PMID- 8471159 TI - Free radicals as mediators of tissue injury and disease. AB - A radical is any molecule that contains one or more unpaired electrons. Radicals are normally generated in many metabolic pathways. Some of these radicals can exist in a free form and subsequently interact with various tissue components resulting in dysfunction. The potential role of oxygen- or xenobiotic-derived free radicals in the pathology of several human diseases has stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. However, because free radical-mediated changes are pervasive and often poorly understood, the question of whether such species are a major cause of tissue injury and human disease remains equivocal. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents. Examples of purported free radical-mediated disorders are discussed in detail to provide insights into the controversy over whether free radicals are important mediators of tissue injury. PMID- 8471160 TI - Stress proteins in aquatic organisms: an environmental perspective. AB - The cellular stress response protects organisms from damage resulting from exposure to a wide variety of stressors, including elevated temperatures, ultraviolet (UV) light, trace metals, and xenobiotics. The stress response entails the rapid synthesis of a suite of proteins referred to as stress proteins, or heat-shock proteins, upon exposure to adverse environmental conditions. These proteins are highly conserved and have been found in organisms as diverse as bacteria, molluscs, and humans. In this review, we discuss the stress response in aquatic organisms from an environmental perspective. Our current understanding of the cellular functions of stress proteins is examined within the context of their role in repair and protection from environmentally induced damage, acquired tolerance, and environmental adaptation. The tissue specificity of the response and its significance relative to target organ toxicity also are addressed. In addition, the usefulness of using the stress response as a diagnostic in environmental toxicology is evaluated. From the studies discussed in this review, it is apparent that stress proteins are involved in organismal adaptation to both natural and anthropogenic environmental stress, and that further research using this focus will make important contributions to both environmental physiology and ecotoxicology. PMID- 8471161 TI - Human TRE17 oncogene is generated from a family of homologous polymorphic sequences by single-base changes. AB - The tre oncogenic locus was identified in transformants receiving human DNA from Ewing's sarcoma cells EW1. Genetic elements of tre originate from chromosomes 5, 18, and 17. The TRE17 oncogene is consistently transcribed in various human cancer cells and proves oncogenic (onc) in expression vector-based assays. Here, the nucleotide sequence of TRE17 with defined noncoding and two coding exons (4,426 nucleotides) was compared with sequences cloned from placental DNA library or generated by polymerase chain reaction (PCR) from EW1 and independent healthy individuals. Cloned sequences displayed restriction site polymorphism, with different patterns for EW1 and normal tissues. Sequence analysis revealed that they originate from a family of homologous sequences alpha, beta, and gamma. TRE17 alpha and less frequent TRE17 beta (similarity score approximately equal to 88%) were found in both normal and EW1 cells. oncTRE17, classified as TRE17 beta, differed from the wild-type TRE17 beta, besides a few intronic changes, by a single-base frameshift insertion in one of the coding exons. TRE17 gamma, so far identified in EW1 but not in normal somatic cells, diverged from oncTRE17 by 6% nucleotide substitutions and by stop codons in each reading frame. The results are consistent with the possibility that TRE17 sequences other than oncTRE17 are translated if alternatively spliced. Expression of TRE17 in normal somatic cells was, however, not yet reported. PMID- 8471162 TI - Immortalization of a fetal rat brain cell line that expresses corticotropin releasing factor mRNA. AB - By introducing the SV40 T antigen under the control of promoter sequences from the gene encoding the rat corticotropin-releasing factor (CRF) into primary cultures from fetal rat brain, a stable cell line was established that expresses the SV40 T antigen and transcribes its endogenous CRF gene. The cell line exhibits neuronal properties, as demonstrated by positive immunostaining with antibodies against neuronal markers, and it provides a useful system for the detailed analysis of the transcriptional regulation of the neuropeptide gene at an early stage of development. Promoter activities of the CRF 5'-flanking region were tested in transient expression assays after transfection of the cell line with different fusion constructs with CRF promoter regions linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. Basal activity of the promoter was determined by DNA sequences between positions -269 and -222 upstream of the transcriptional start site and showed weak induction upon treatment with forskolin. PMID- 8471163 TI - Structure of the gene coding for the human retinoic acid-inducible factor, MK. AB - The retinoic acid-inducible MK gene shows a distinct developmental pattern of expression, which implies that it has potential growth regulation and differentiation functions, particularly in the brain. We report here the cloning of the human MK gene from a phage library constructed from placental tissue. The structure of this gene has been determined using Southern hybridization and DNA sequence analysis. An isolated fragment was cloned and found to contain sequences identical to those of a previously isolated human MK cDNA clone, MKHC4. The gene contains three introns within the MK coding region as well as additional sequence, which indicates the presence of an intron prior to the putative protein start site. As judged by sequence analysis of cDNA clones, primer extension studies, and Northern analysis, the most abundant human MK message corresponds to the major mRNA of the previously described mouse gene. Primer extension studies and cDNA sequence data suggest that minor messages may be transcribed from the human gene, but no evidence of additional messages has been found by Northern analysis. This is in contrast to the mouse MK gene, from which three mRNAs are transcribed. Nevertheless, the similarity in the overall genomic structure of the human and mouse genes is striking. PMID- 8471164 TI - Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome. AB - Genomic blot analysis revealed that the nucleophosmin/B23 gene belongs to a multigene family that has about 10 copies per haploid human genome. In searching for human nucleophosmin/B23 functional genes, seven processed pseudogenes (NG1 1.6, NG2-6, NG3-3, NG4-5, NG5-4, NG6-4, and NG7-6) were isolated and characterized. Four of them, NG2-6, NG3-3, NG4-5, and NG7-6, contain the sequences corresponding to the full-length cDNA. NG1-1.6 is 5'-truncated, whereas NG5-4 and NG6-5 are 3'-truncated pseudogenes. Of the seven pseudogenes, NG3-3 clone has the longest 5' untranslated sequence, which contains 104 nucleotides upstream of the translation initiation codon (AUG). Two processed pseudogenes (NG2-6 and NG3-3) have different polyadenylation sites from the mRNA, indicating the usage of alternative polyadenylation signals at the 3' sequence. PMID- 8471165 TI - Oligodeoxynucleotides capable of binding to GC-rich regions in DNA are inappropriately synthesized during random hexanucleotide-primed labeling reactions. AB - Random hexanucleotide labeling is a commonly used and powerful technique for preparing radiolabeled nucleic acid probes. Because of the dependence of DNA polymerase upon single-stranded DNA as a template, the technique should theoretically also be useful for detecting small amounts of single-stranded DNA in the presence of a larger amount of double-stranded DNA. In the course of such an experiment, we identified an unexpected reaction that could contribute to background problems often encountered during Southern and Northern blotting. In the complete absence of template, random hexanucleotides appear capable of functioning both as template as well as primer, giving rise to labeled oligonucleotides as large as 20-mers. Some of these bind very tightly to GC-rich regions in target DNA immobilized on membranes, resisting high-stringency washing conditions. By choosing shorter incubation times and including sufficient single stranded template, the problem may be minimized. PMID- 8471166 TI - Binding constant determination studies utilizing recombinant delta CREB protein. AB - In this study, we report the binding constants (Kd) of the cAMP-responsive element binding protein (delta-CREB) for various cAMP-response element (CRE) motifs. We utilized purified recombinant delta CREB protein in binding reactions with natural CRE motifs found in the promoter of two neuropeptide hormone genes and with several variant CRE motifs. The Kd of delta CREB for the perfectly palindromic CRE, TGACG-TCA, found within the somatostatin promoter is estimated to be 5.0 x 10(-9) M. The Kd of delta CREB for the variant CRE motif TG_CGTCA found within the enkephalin promoter is calculated to be in the 3 x 10(-8) M. These studies provide an in vitro quantitative assessment of the binding affinity of delta CREB for various CRE motifs. PMID- 8471167 TI - Immobilization and recovery of fusion proteins and B-lymphocyte cells using magnetic separation. AB - A new approach to facilitate immobilization and affinity purification of recombinant proteins and selected human B lymphocytes has been developed. Using magnetic beads with attached DNA containing the Escherichia coli lac operator, fusion proteins comprising the DNA-binding lac repressor could be affinity purified and recovered by gentle elution conditions, such as with a lactose analogue or by enzymatic means using either deoxyribonuclease (DNase) or restriction endonucleases. The results show for the first time that a DNA-binding protein can be used for affinity purification of fusion proteins as exemplified by the specific and gentle recovery of beta-galactosidase and alkaline phosphatase from bacterial lysates using immunomagnetic separation. The approach was further extended to cell separation by the efficient recovery and elution of human CD37 B lymphocytes from peripheral blood. PMID- 8471168 TI - [Surgical treatment of cranial dysostosis with internal fixation method]. AB - We present our experience using plates and screws for the fixation of craniofacial mobilizations. We describe the osteotomies "monoblock advancement" combined or not with "facial bipartition", used for the treatment of Crouzon's disease and Apert's syndrome respectively. We expose our experience gained on 42 patients with a follow up of six years, pointing out the indications for plates and screws. The advantages of this method are discussed, being mainly these: stable fixation, early surgery and no intermaxillary fixation needed. PMID- 8471169 TI - [Fatty and muscular areas of the arm: indicators for the nutritional evaluation of pre-school children]. AB - The assessment of skinfold thickness has been used to estimate protein reserve through arm muscle area (AMA) and through arm fat area (AFA) it can assess caloric reserve. The aim of this paper is to compare trends of AMA in pre-school children living in Tijuana with american children of the same ages. This study has been accomplish in pre-school children attending to the Federal Education System. Through a randomly sample it was chosen 30 school, afterwards in systematic was done to assess 900 children aged 48 to 78 months old. This studied variables were: weight, height, arm circumference and triceps skinfold thickness, obtained according to accepted techniques at the international literature. From which were created AMA and AFA, according to formulas already described. A multiple regression model was obtained from AMB to height, between expected and experimental values. Using analysis of variance to determined differences between slopes and intercepts. In this paper are shown the statistics and distributions for AMA and AFA. Correlations for reference and experimental values were linear and no significant differences were observed between the slopes and intercepts of the set of data. These results suggest that form the point of view considering AMA, growth rate between Tijuana children and American similars are apparently the same at this ages. PMID- 8471170 TI - [Subependymal/intraventricular hemorrhage in preterm newborn infants. Neurodevelopmental course during the first year of life]. AB - Subependymal/intraventricular hemorrhage (SE/IVH) is the most frequently encountered type of hemorrhage in the neonatal period. Premature infants often develop SE/IVH which remains is one of most serious neonatal events. We studied a group of 96 premature newborn infants: half of which were diagnosed with SE/IVH. We evaluated the babies at six and 12 months of age which++ a battery of neurobehavioral exams, including neurological, psychological, motor an audiological test. In 52 of infants with SE/IVH showed some type of neurobehavioral abnormality, compared with 13% of non-SE/IVH infants. In 56% of SE/IVH infants had neurological abnormalities at 12 months (P < 0.0001) difference with non-SE/IVH), predominantly in areas of muscle tone and reflex. Motor abnormalities were encountered in 42% of SE/IVH children, and in 4% of non SE/IVH children at 12 months. Psychometric abnormalities at 12 months were noted in 53% of the SE/IVH group. Hypocusis were noted in 38% of the SE/IVH group and in 15% of the non-SE/IVH group. PMID- 8471171 TI - [Risk factors associated with the development of leukemia in children]. AB - INTRODUCTION: Leukemia is the most frequent neoplasia in children; in our country it is the main cause of medical attention in children with cancer. The are different risk factors associated with the development of this kind of cancer. OBJECTIVE: To identify which of the already known factors described in the literature associated with the development of leukemia are most frequent in the pediatric population of Mexico City. MATERIAL AND METHODS: A protective case control study was carried out using prevalent and incident cases. In two third level hospitals of Mexico City, a total of 81 children who had been diagnosed as suffering from different kind of leukemia, confirmed by biopsy of bone marrow, were select and studied. The control were 154 children from two different sources: 77 of them came from the same hospital where the cases received medical care, the selection criteria was not to have any kind of neoplasia; and 77 came from the same community where those diagnosed children cases lived, the selection criteria for this group was that they were healthy children. Both cases and community controls were visited at home and interview to complete precoded questionnaire with the different variables of the study. The information from the hospital controls was obtained during the time they stayed in the hospital. Odds ratio (OR's) for the different associations were calculated, as well as its confidence intervals at 95% (IC) accord to Cornfield and unconditioned logistic regression was carried out to control confounding variables. RESULTS: OR greater than 1 was found in those with familiar cancer background 1.93 (1.2-3.63); the mother being exposed to X-ray during pregnancy 1.89 (0.84-4.22); previous abortions before the child with leukemia was born 2.44 (1-06-5.68); being born from full term birth 2.42 (0.47-16.65); being born with weight greater that 3500 g 2.21 (1.04-4.33); being exposed to fertilizers 4.73 (1.04-24.14) and insecticides 1.93 (1.05-3.56). OR smaller than 1 was found in those who have been in a hospital because of an infectious disease during the first year of life 0.57 (0.17-1.74); to have suffered from chicken pox 0.59 (0.32-1.08). No association to parent's age or job was found. Multivariated analysis shows that the exposure to insecticide is the most important risk factor associated with the development of leukemia in children. CONCLUSIONS: We obtained positive associations to different risk factors described in the literature, having found that exposure to fertilizers is the most important risk factor and finding no association with the parent's occupation. This leads to the need of carrying out further studies to investigate, in more detail, the occupation of the father to confirm whether or not this is a risk factor. PMID- 8471172 TI - [Acute appendicitis in the first 3 years of life: presentation of 72 cases and review of the literature]. AB - The appendicitis in infants, including premature and newborn are exceptional. In smallers of three years is few frequently and plenty they are driving to fulfill the laparotomy. Diagnostic is hard for the atypical clinical picture and the rapid evolution toward appendicular boring and generalized peritonitis, modified or not for antibiotics use. The main symptoms of appendicitis finding in this study were: fever, vomitus, pain and abdominals distention. To research the muscular resistance become generalized, the McBurney signs and bonce. There were leucocytosis, urine alterations and the "X"-rays films showed occlusion signs and paralytic ileo. The ultra-sound scan were of great utility in the diagnostic of acute appendicitis and its complications, abscess of walls of intraperitoneal. There surgery was be urgent. The insiction for right half supra and infraumbilical become more frequently, next with appendicectomy of Oschner. Were utilized drain pipe in perforating or abscess cases. The post-operative complications more frequent seen were infection on the surgical hurt. The supured and gangrened appendicitis and perforated and abscessed walls were treated with antibiotics. The mortality rate were zero in this analyzed group. PMID- 8471173 TI - [Antiphospholipid syndrome: a new diagnostic option in rheumatology in children. Analysis of 3 clinical cases]. AB - There are some patients with a clinical picture that suggests to be a rheumatological problem. However, it does not have all the criteria to be accepted such as specific problems like systemic lupus erythematosus, juvenile rheumatoid arthritis, etc. Now we know that a relation between high levels of antiphospholipid antibodies exist in these special patients and the name of the disease is antiphospholipid syndrome. This problem can be primary or secondary. This disease has been studied mainly in adults with SLE an there is not a description of this syndrome in national pediatric literature. For this reason we present three clinical cases that permit us to review both forms of the syndrome. In this way we alert want to the pediatric community about this topic, and if the number of cases increases, it will improve the knowledge and prognosis of the patients at this age. PMID- 8471174 TI - [Disseminated histoplasmosis in pediatrics. Report of a case]. AB - We report a case of a female infant, from Acapulco Guerrero, Mexico. She had been sick for 45 days, with diarrhea and general malaise, fever during the last 20 days; at physical examination she was pale, with abdominal distention and hepatosplenomegaly. She had leukopenia, thrombocytopenia and anemia. The microscopic findings in the bone marrow sample were intracytoplasmic and extracellular bodies. Both bone marrow and blood cultures were positive for Histoplasma capsulatum. Seventy three pediatric cases of diseminated histoplasmosis have been described in the medical literature since 1934 to 1988. It is know that only about 1% of the persons that become infected will develop a diseminated disease. PMID- 8471175 TI - [Sudden death syndrome in childhood. Current recommendations for its possible prevention]. AB - The sudden infant death syndrome (SIDS) has a prevalence of 0.31 to 3.5 per 1000 live newborns. It has its peak between two and four months with a greater incidence in the winter season. This syndrome should be diagnosed only after a careful post-mortem examination and a review of the death scene. The babies with SIDS have physiologic differences in their autonomic nervous system when compared with control groups. These babies have a history of excessive room heating and infant bedding. In addition the position most commonly used to put these infants to bed is the prone position. Changes in the way these infants are put to bed, changing from prone to supine position, have led to a significative reduction in SIDS. In order to decrease accidental death by asphyxia, pillows filled with polysterene beads should be avoided. PMID- 8471176 TI - [Hyaline membrane disease]. PMID- 8471177 TI - Microbial metabolism of quinoline and related compounds. XVI. Quinaldine oxidoreductase from Arthrobacter spec. Ru 61a: a molybdenum-containing enzyme catalysing the hydroxylation at C-4 of the heterocycle. AB - Quinaldine oxidoreductase from Arthrobacter spec. Ru 61a converts quinaldine to 1H-4-oxoquinaldine. The enzyme was purified 70-fold to apparent homogeneity in a 5-step procedure with a recovery of 4%. The molecular mass of the native enzyme was calculated to be 340,000 Da by gel filtration. SDS-polyacrylamide gel electrophoresis of the enzyme revealed 3 protein bands corresponding to 82,000 Da, 35,000 Da and 22,000 Da. The enzyme contained 1.6 atoms of molybdenum, 8 atoms of iron, 8 atoms of acid labile sulfur, 2 molecules of FAD and as part of the molybdenum cofactor, molybdopterin cytosine dinucleotide. Due to the composition of the cofactors the quinaldine oxidoreductase belongs to the class of molybdo-iron/sulfur-flavoproteins. Cyanide, arsenite and 4 hydroxymercuribenzoate were effective inhibitors whereas the enzyme was not affected by methanol. PMID- 8471178 TI - Amino-acid sequence of the alpha D- and beta-polypeptide chains of the Japanese quail hemoglobin. AB - Two hemoglobin components are recognized in the erythrocytes of the adult Japanese quail: a major (Q-II) and a minor (Q-I) component. We have determined the amino-acid sequence of the alpha D-globin of the minor component and the beta globin which is common to both components by conventional protein sequence analysis. The sequences of both the alpha D- and the beta-globins showed close homology with those of their counterpart constituents in other avian hemoglobins. Proline at position 119 in the alpha D-globin which is known to be critical for the altitude respiration by the alpha 1 beta 1 interface is conserved in the Japanese quail hemoglobin. PMID- 8471179 TI - Actin-sequestering ability of thymosin beta 4, thymosin beta 4 fragments, and thymosin beta 4-like peptides as assessed by the DNase I inhibition assay. AB - Thymosin beta 4 containing 43 amino-acid residues belongs to a family of highly homologous peptides present at high concentrations in various species, cells, and tissues. Safer et al. [J. Biol. Chem. 266, 4029-4032 (1991)] have shown that thymosin beta 4 is an actin-sequestering peptide. Because DNase I is inhibited by G-actin and not by F-actin we employed this enzymatic assay to determine the actin sequestering properties of 4 other thymosin beta 4-like peptides and fragments of thymosin beta 4 generated by enzymatic digestions. Thymosin beta 4 sequesters G-actin at a 1 to 1 ratio an thereby inhibits its polymerisation to F actin in high salt solution. The oxidation of the single methionine residue at position 6 does not abolish its actin-sequestering properties. However neither thymosin beta 4 24-43 nor thymosin beta 4 13-43 inhibit the polymerisation of G actin. We conclude from this that some structural features in the amino-acid sequence of thymosin beta 4 before position 13 are obligatory for its biological function. Oxidized thymosin beta 4 (beta 4-sulfoxide) as well as four other thymosin beta 4-like peptides were shown to be actin-sequestering peptides like thymosin beta 4. PMID- 8471180 TI - Subsite affinities of Aspergillus niger glucoamylase II determined with p nitrophenylmaltooligosaccharides. AB - Kinetic parameters were obtained for glucoamylase catalysed hydrolysis of substrates of an alpha-(1,4)-maltooligosaccharide series and of a p-nitro-phenyl alpha-maltooligosaccharide series. p-Nitrophenyl substrates of chain length 11 and 17 were synthesized in 97% and 95% purity, respectively, to test the significance of binding at remote subsites. The affinities of the subsites > 4 are demonstrated to be insignificant. The subsite binding contributions for D glucopyranosyl and for p-nitrophenyl residues were calculated. PMID- 8471181 TI - Alterations in lipid characteristics of lysosomes are involved in liver necrosis induced by thioacetamide. AB - To determine whether lysosomal lipid composition is altered in hepatic necrosis, we studied this parameter in thioacetamide-induced necrosis and in its regenerating stage as well as in the recovery of thioacetamide-induced injury. Results showed that in liver necrosis there is an increase in the protein and phospholipid lysosomal contents. This effect may be related to an increased number of lysosomes. These organelles also suffered a decrease in cholesterol content. When liver necrosis was recovered either pharmacologically or spontaneously all three parameters recovered their normal values. These results suggest that lysosomes and their lipid composition play a role in progression of hepatic necrosis. PMID- 8471182 TI - Thimet oligopeptidase--a review of a thiol dependent metallo-endopeptidase also known as Pz-peptidase endopeptidase 24.15 and endo-oligopeptidase. AB - Thimet oligopeptidase (EC 3.4.24.15) is a thiol-dependent metallo-endopeptidase also known as Pz-peptidase, collagenase-like peptidase, endooligopeptidase A, soluble metallo-endopeptidase and endopeptidase 24.15. The enzyme is closely related to the yeast proteinase yscD. Thimet oligopeptidase (M(r) 74000) is widely distributed in animals and plants. In rat liver it exists in a cytoplasmic and mitochondrial form; a membrane-bound form of the enzyme was discovered in rat brain. Thimet oligopeptidase hydrolyses small peptides but does not act on proteins. In rat brain thimet oligopeptidase is involved in the generation of enkephalins and inactivation of bioactive peptides and experiments with yeast provided good evidence that the enzyme is involved in the late stages of cytoplasmatic protein degradation. PMID- 8471183 TI - Marketing aspects of company-sponsored postmarketing surveillance studies. PMID- 8471184 TI - Theophylline. Current thoughts on the risks and benefits of its use in asthma. AB - Theophylline and its derivatives have been used in the treatment of asthma for over 50 years, but since the advent of more potent bronchodilators their use has become cloaked in controversy. Their continued existence results from their undoubted usefulness in severe acute asthma, nocturnal asthma, childhood asthma and moderate to severe chronic airflow limitation, and because of habitual use by physicians in other situations. The precise mechanism of action of theophylline remains uncertain. The role of phosphodiesterase inhibition and adenosine antagonism has been reviewed and the clinical significance of the anti inflammatory action of theophylline discussed. Theophylline has unpredictable metabolism when first administered, and continued monitoring of drug concentrations is essential. Commonly encountered adverse effects may occur at therapeutic serum concentrations, frequently necessitating drug withdrawal. The overlapping therapeutic and toxic theophylline serum ranges can lead to life threatening adverse effects at the upper end of the therapeutic range, especially in the elderly in whom special precaution is required. PMID- 8471185 TI - Comparative tolerability profiles of thrombolytic agents. A review. AB - The 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required. PMID- 8471186 TI - Drug interactions of clinical significance with opioid analgesics. AB - Opioid analgesics and other drugs interact through multiple mechanisms, resulting in pharmacological effects that depend upon the pharmacodynamic action studied, the interacting agents and the route of administration. Many interactions result from induction or inhibition of the hepatic cytochrome P450 mono-oxygenase system. The elimination of opioids is largely dependent on hepatic metabolism, and drug interactions involving this mechanism can therefore be clinically significant. Antibiotics are often used concomitantly with opioids in patients undergoing medical or surgical procedures; the best documented metabolic interactions are with erythromycin and rifampicin (rifampin). Erythromycin increases and rifampicin decreases the effects of opioids. Cimetidine may increase the effects of opioids by increasing their duration of action; there have been no documented cases of interactions with ranitidine. Carbamazepine, phenytoin and the barbiturates can enhance the metabolism of opioids that rely on hepatic metabolism. Other pharmacokinetic interactions include those with benzodiazepines, tricyclic antidepressants, phenothiazines and metoclopramide. Interactions involving pharmacodynamic mechanisms are more common than pharmacokinetic ones. Such interactions are manifested clinically as as a summation (additive or synergistic) of similar or opposing pharmacological effects on the same body system. Idiosyncratic interactions also occur, the mechanisms of which have not been proven to be solely modulated by either pharmacokinetic or pharmacodynamic means. The knowledge of particular opioid-drug interactions, and the causative pharmacokinetic, pharmacodynamic, and idiosyncratic mechanisms, allows for the safer administration of opioid analgesics. PMID- 8471187 TI - Risk-benefit assessment of nicotine preparations in smoking cessation. AB - Nicotine influences many risk factors for cardiovascular disease, peptic ulcer disease, pregnancy complications and wound healing; however, whether nicotine itself actually causes or aggravates these diseases has not been well demonstrated. The safety of nicotine preparations for smoking cessation depends on the population, formulation, route of administration, dose, and frequency and duration of use. Major adverse effects of nicotine polacrilex and transdermal nicotine are very rare. Nicotine therapy usually doubles long term abstinence rates and is especially beneficial to highly dependent smokers. Nicotine replacements produce lower nicotine concentrations than cigarettes, and no tar and carbon monoxide; thus, it is difficult to justify absolute contraindications to these products. Decisions on the use of nicotine preparations in pregnancy, coronary disease, etc., must consider not only the medical status of patients but also their likelihood of stopping smoking with and without the help of nicotine replacement. PMID- 8471188 TI - Effects of exogenous lipids on cancer and cancer chemotherapy. Implications for treatment. AB - The addition of fatty acids to the diets of tumour-bearing animals results in specific and defined structural modification of the tumour membrane lipids without disrupting the cell. Furthermore, fatty acids at higher concentrations may act directly as anticancer agents, and there is evidence of selective sensitivity of neoplastic cells. Similarly, experimental enrichment of the diets with specific lipids modulates carcinogen-induced tumorigenesis at the initiation or promotion steps, and in some animal models, the growth rate of established tumours. Therefore, anticancer therapies which utilise lipid-based strategies may be useful clinically. Although dietary strategies used alone may have some favourable effect, it seems likely that the combination of diet with anticancer drugs has the best possibility of providing the extent of cytotoxicity required for tumour eradication. Such combinations could take advantage of an additive effect of each, or could act synergistically such as by the influence of dietary fatty acid modification on drug transport. However, dietary lipids may also increase the toxicity of anticancer drugs to normal tissues and decrease the therapeutic index. Further research is needed to define the role of lipids in future chemotherapy. PMID- 8471189 TI - Acute amitriptyline withdrawal and hyponatraemia. A case report. AB - The tricyclic antidepressants (TCAs) are commonly used in the treatment of depression and, perhaps due to the nature of the condition being treated, figure prominently in cases of deliberate overdosage, where the toxicity of amitriptyline has been well established. However, the abrupt cessation of TCA administration can also be detrimental to the patient, triggering withdrawal phenomena often characterised by an exacerbation of the symptoms for which the patient was originally treated. We present a biochemically proven case of amitriptyline withdrawal where the clinical features at presentation made it difficult to distinguish from acute toxicity. The patient's neurological signs and distended bladder suggested amitriptyline toxicity, whereas the history and signs of cholinergic hyperactivity were consistent with acute withdrawal. The diagnosis was confirmed at a later date when further history and a biochemical analysis of plasma TCA concentrations became available. Hyponatraemia may have exacerbated the condition of the patient, whether or not it was caused by amitriptyline. PMID- 8471190 TI - Carbamazepine overdose. Features of 33 cases. AB - Review of the medical records of 2 major adult teaching hospitals for a 4-year period revealed 33 instances of carbamazepine overdose. These patients had a mean age of 30 years and 58% were known epileptics. They ingested a mean of 12g carbamazepine (range 1.6 to 45g), with 51% of cases involving other drugs, particularly alcohol. The clinical manifestations of toxicity formed a recognisable clinical picture of diminished conscious state (100% of patients), mydriasis (42%), abnormal muscle tone and tendon reflexes (55%) and ataxia, nystagmus or ophthalmoplegia (48%). 24% of cases were complicated by seizures. The incidence of hyperglycaemia and hypokalaemia were related to higher drug concentrations. 12% showed hyponatraemia and 50% had transient evidence of hepatic dysfunction. The pharmacokinetic properties of carbamazepine play a role in determining management strategies. Management is largely supportive through avoidance of drug interactions, large doses of activated charcoal, careful airway management and correction of electrolyte disturbances. PMID- 8471191 TI - Biology of Toxoplasma gondii. AB - In conclusion, a large body of new information on the biology and immunology of T. gondii has accumulated in the past several years. Much of this is due to the advent of AIDS and the increased funding made available to researchers interested in opportunistic infections in this patient population. These scientific advances have led to a better understanding of the process by which Toxoplasma infects mammalian host cells, molecular biology and biochemistry of the parasite, antigenic structure and immune response to the infection and approaches to be adopted for drug design and therapeutic strategies. Thus, it is through such recognition of the importance of understanding the basic science of an opportunistic pathogen that such advances can be realized. PMID- 8471192 TI - HIV-1 infection and modulation of cytokine and growth factor expression in Kaposi's sarcoma-derived cells in vitro. AB - OBJECTIVES: HIV-1 transcripts have been detected in AIDS-related Kaposi's sarcoma (KS) tissues within the factor XIIIa + dermal dendrocytes present in the tumor. Various cytokines and growth factors have been shown to influence the growth of KS-derived cells in vitro. HIV-1 preferentially infects CD4+ cells and has also been found to infect some CD4- cells in vitro. The susceptibility of cultured KS cells in vitro to infection with HIV-1 and the expression of interleukin (IL)-1 beta, IL-6 and basic fibroblast growth factor (bFGF) after exposure to HIV-1 was examined. METHODS: The susceptibility of two different KS-derived cell cultures to HIV-1 infection was examined by the expression of p24 antigen, detection of proviral sequence and electron microscopy. The expression of IL-1 beta, IL-6 and bFGF was detected by enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. RESULTS: KS-derived cells can be infected by HIV-1 in vitro. Both KS-derived cells were found to express CD4 mRNA. The expression of IL 1 beta and IL-6 was increased, whereas the expression of bFGF was not stimulated after exposure of KS cells to HIV-1. CONCLUSION: These experiments describe the in vitro infection of KS-derived cells by HIV-1 and the expression of various cytokines and growth factor following infection. The increased production of cytokines observed following such infection may be involved in the pathogenesis of AIDS-related KS. PMID- 8471193 TI - Fibroblast-derived factors preserve viability in vitro of mononuclear cells isolated from subjects with HIV-1 infection. AB - OBJECTIVE: Peripheral blood mononuclear cells (PBMC) from HIV-infected subjects have an increased mortality rate (MR) when incubated in vitro for 3 days in a culture medium. We have previously shown that fibroblast-conditioned medium (FCM) can preserve viability, without significant activation, of human lymphocytes in vitro. We therefore tested the ability of two FCM and other factors to reduce spontaneous MR in HIV-positive PBMC. METHODS: PBMC were cultured for 3 days in control medium and medium supplemented with FCM or recombinant cytokines [interleukin (IL)-2, IL-6, IL-7, granulocyte macrophage colony-stimulating factor]. Cells viable at day 3 were counted in a cytofluorimeter after staining with ethidium bromide. DNA was extracted from the cultures and evaluated for the presence of low molecular weight fragmentation. RESULTS: The MR of PBMC from 51 HIV-positive subjects and from 21 healthy controls were 30.1 and 9.5%, respectively (P < 0.0001). The MR was higher in 40 patients with a CD4+ lymphocyte count < 400 x 10(6)/l than in subjects with a count > 400 x 10(6)/l (32.84 versus 20.96%; P = 0.047). IL-2 and FCM significantly reduced MR in HIV positive subjects (MR: 17.8 and 20.4%; P: < 0.001 and 0.005, respectively). This effect was more evident in subjects with a CD4+ lymphocyte count < 400 x 10(6)/l and in subjects with negative p24 antigenaemia. Cellular proliferation accounts for increased survival in IL-2-supplemented cultures but not in those with FCM. DNA was extracted from fresh PBMC and cells cultured for 3 days for 22 HIV positive cases. DNA degradation was documented and bands related to an apoptotic mechanism of death observed, especially in subjects with more advanced disease. CONCLUSIONS: Our data suggest that FCM inhibits accelerated cell death in vitro of PBMC isolated from HIV-positive patients. PMID- 8471194 TI - Effects of retroviral infections on immune function in African-American intravenous drug users. AB - OBJECTIVES: To determine the effect of retrovirus infection and co-infection, and intravenous substance use, on immune function in African-Americans. DESIGN: A cohort of South Florida street-recruited African-American intravenous drug users formed the study population. The cohort consisted of 90 HIV-negative & human T lymphotropic virus (HTLV)-negative, one HIV-negative & HTLV-I-positive, 11 HIV negative & HTLV-II-positive, 79 HIV-positive & HTLV-negative, one HIV-positive & HTLV-I-positive and 21 HIV-positive & HTLV-II-positive individuals. The results reported are for the cross-sectional, baseline assessment of immune parameters. METHODS: Lymphocyte phenotypic distributions and functional markers, including proliferative response to mitogens and natural killer cell cytotoxicity, were determined. Serum immunoglobulin (Ig) levels were determined as a measure of B cell activity. RESULTS: HTLV-II infection was associated with increases in CD8 lymphocyte count and serum Ig, but with no other significant immunologic changes. The distribution of CD4 and CD8 percentages, CD4:CD8 ratio, phytohemagglutinin (PHA) and pokeweed mitogen (PWM) reactivity, IgA and IgG for the four retrovirus serostatus groups suggested the possibility of interactive effects in the co infected group, as demonstrated by a trend toward lower medians for CD4 and for PHA and PWM response and higher medians for IgG, IgA and CD8. Retrovirus seronegative intravenous drug users had significantly impaired immune status compared with non-drug-using control individuals. CONCLUSIONS: Immunologic dysfunction attributable to HTLV-II infection was minor compared with HIV infection in this population. Study subjects who were co-infected with HIV and HTLV demonstrated more impairment of immune function than individuals with single retrovirus infections. PMID- 8471195 TI - Highly specific V3 peptide enzyme immunoassay for serotyping HIV-1 specimens from Thailand. AB - OBJECTIVE: To develop and evaluate a simple V3 peptide-based enzyme immunoassay (EIA) for large-scale serotyping of HIV-1 specimens from Thailand. DESIGN: Serologic reactivities with synthetic peptides derived from the V3 loop of gp120 were used for typing HIV-1 specimens. METHODS: Synthetic peptides PND-A and PND B, derived from the consensus amino-acid sequences of the V3 loop of gp120 from two major genomic variants of HIV-1 in Thailand (A and B), were evaluated in an EIA on 61 Thai HIV-1 sera for which genotypes had been determined by polymerase chain reaction. The peptide EIA was then applied to sera from 188 HIV-1-infected patients, selected in non-random, convenience samples of known risk groups from four geographic regions of Thailand. RESULTS: The sensitivities and specificities of PND-A and PND-B were 86% (30 out of 35) and 96% (25 out of 26) and 92% (24 out of 26) and 94% (33 out of 35), respectively, with 100% predictive values of a monoreactive positive test for both peptides. The assay classified 101 specimens as serotype A, 39 as serotype B, eight as serotype AB (dually reactive), and 40 as untypable (non-reactive). Excluding dual reactors and non-reactors, 92% (77 out of 84) of specimens from patients probably infected by sexual contact were serotype A; conversely, 76% (28 out of 37) of injecting drug users were serotype B. CONCLUSION: The serologic results corroborated previous findings, in a smaller subset of samples, of an apparent segregation of viral subtypes by mode of transmission, suggesting two separate HIV-1 epidemics in Thailand. This peptide EIA could be a valuable epidemiologic tool in determining the dynamics of the rapid spread of HIV-1 in Thailand. PMID- 8471196 TI - Evaluation of mechanical transmission of HIV by the African soft tick, Ornithodoros moubata. AB - OBJECTIVES: To assess the ability of the African Hut Tampan, Ornithodoros moubata, to mechanically transmit HIV-1 and to re-appraise HIV-1 infectivity in an arthropod cell line at 28 and 35 degrees C. DESIGN: To evaluate HIV-1 transmission by O. moubata, as determined by HIV-1 survival, 'blood-meal' size and interval between feeds, various tick developmental stages were allowed to feed on a heavily infected lymphoblast-rich blood-meal containing HIV-1BRU in an in vitro feeding chamber. METHODS: Blood-meal regurgitation was evaluated using 51Cr-labelled human erythrocytes, and human lymphoblast survival in ticks using Trypan blue. HIV-1 survival in ticks was evaluated by reverse transcriptase activity in tick homogenates cocultured with CEM lymphoblasts. Polymerase chain reaction and Southern blot analysis were used to detect proviral HIV-1 in arthropod cells in vitro. RESULTS: HIV-1BRU remained viable for up to 10 days with O. moubata adults. This is the longest recorded survival of HIV in an arthropod. In agreement with other studies. O. moubata regurgitated part of its previous blood-meal into the feeding lesion. Human CEM lymphoblasts partially survived for up to 7 days at 28 and 35 degrees C inside O. moubata's digestive tract. The blood-meal of adult female ticks was as high as 240 microliters (approximately 70 times more than a mosquito), while the most likely potential mechanical vectors (fourth- and fifth-stage nymphs) ingested an average of 39 microliters (maximum, 73 microliters), with some ticks re-feeding as early as 14 days postfeed in the absence of a moult. Shortcomings associated with the experimental protocol suggest that HIV survival within O. moubata may reach 14 days following natural infection, or that ticks might re-feed earlier. Although HIV-1BRU and HIV-1NDK were unable to replicate at 28 and 35 degrees C in CD4- Aedes albopictus C6/36 mosquito cells, HIV-1NDK was detected in its proviral form. CONCLUSIONS: Our investigations showed that mechanical transmission of HIV 1 by O. moubata is unlikely to occur in the laboratory. This may not be the situation under field conditions. PMID- 8471197 TI - The natural history of cryptosporidial diarrhoea in HIV-infected patients. AB - OBJECTIVE: To determine the natural history of cryptosporidial infection in HIV infected individuals. DESIGN: Retrospective study. SETTING: University teaching hospital HIV inpatient and outpatient unit. PATIENTS: Thirty-eight HIV-infected patients presenting with cryptosporidial diarrhoea between April 1986 and July 1991 were identified retrospectively from laboratory records. RESULTS: Eleven of the 38 patients had a clinical remission of their diarrhoea. Median lymphocyte count of the remission group was significantly higher than that of the non remission group (1100 and 550 x 10(6)/l, respectively; P = 0.003). Median survival times were 66 and 11.5 weeks for the remission and non-remission groups, respectively (P = 0.001). Liver function tests performed at the initial diagnosis of cryptosporidial diarrhoea were available for 28 patients. Aspartate transaminase was raised in 16 and alkaline phosphatase in 10 of these 28 patients. Ten patients showed evidence of AIDS-associated sclerosing cholangitis, one patient had an episode of acute pancreatitis and another presented with acute cholecystitis. CONCLUSIONS: This study suggests that HIV-associated cryptosporidial diarrhoea does not have a uniformly poor prognosis. Eleven out of 38 patients had a spontaneous clinical remission, which appears to be predicted by the absolute lymphocyte count. Abnormal liver function tests and hepatobiliary disease were common. PMID- 8471198 TI - Utility of dapsone for prophylaxis of Pneumocystis carinii pneumonia in trimethoprim-sulfamethoxazole-intolerant, HIV-infected individuals. AB - OBJECTIVE: To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients. DESIGN: Retrospective chart review of patients followed-up to 22 May 1992. SETTING: Infectious diseases outpatient clinic of a tertiary care center in suburban New York City. PATIENTS: Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX. MAIN OUTCOME MEASURES: Patients were followed clinically and with laboratory testing at approximately monthly intervals. RESULTS: Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up. CONCLUSION: Approximately 40% of TMP-SMX intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed. PMID- 8471199 TI - Elevated serum levels of neopterin but not beta 2-microglobulin in HIV-1 seronegative injecting drug users. AB - OBJECTIVE: To determine whether injecting drug use is associated with cellular immune activation in the absence of HIV-1 infection. DESIGN: Serum levels of neopterin and beta 2-microglobulin (beta 2M) were measured cross-sectionally in injecting drug users (IDU) enrolled in a prospective study. SUBJECTS AND METHODS: Two hundred and nineteen HIV-1-seronegative, healthy heterosexual black male IDU aged 21-49 years were selected from the Baltimore-based AIDS Linked to Intravenous Experiences (ALIVE) study. The possibility of including subjects in the process of seroconverting to HIV-1 was minimized by restricting the study to individuals who remained seronegative 6 months after the specimens used for analysis were collected. RESULTS: Mean serum beta 2M levels were not statistically different among groups of IDU whose usual pattern of injection was at least once a day for up to 3 consecutive days (daily users; n = 65), less than once per day (less-than-daily users; n = 75), or not at all for at least 2 weeks (non-recent users; n = 79). In contrast, the mean neopterin level was significantly (P = 0.039) greater in daily users (6.17 nmol/l) than in the other two groups (5.07 and 5.19 nmol/l, respectively, which were not statistically different). These results were not affected, by the frequency of using borrowed non-sterile works or by other demographic and risk factor variables. CONCLUSIONS: Frequent injecting drug use may be independently associated with a small elevation of serum neopterin levels, but not beta 2M levels. Although the occurrence of a type I error in this sample cannot be completely excluded, serum neopterin may be more sensitive than serum beta 2M in detecting activation of immunocompetent cells associated with frequent injecting drug use in this population. PMID- 8471200 TI - Hepatomegaly with severe steatosis in HIV-seropositive patients. AB - OBJECTIVE: To describe death attributed to severe hepatomegaly and macrovesicular steatosis without inflammation or necrosis in HIV-seropositive patients without AIDS. PATIENTS: Patients from the AIDS Clinical Trials Group (ACTG) Adverse Reactions and the Food and Drug Administration's (FDA) Spontaneous Report databases. RESULTS: Six fatal and two non-fatal cases in which no known cause of hepatic steatosis could be found were identified. With one possible exception, none of the six fatal cases had a diagnosis of AIDS and all were in reasonable nutritional status (as indicated by weight and/or serum albumin); the majority were mildly to moderately overweight. All had received at least 6 months of antiretroviral therapy, and all had gastrointestinal complaints without other non hepatic abdominal pathology. At least three out of the six had no history of progressively abnormal liver function tests until a few weeks prior to the onset of symptoms and subsequent death. Further investigation of the FDA and ACTG databases identified two similar but non-fatal cases in which abnormalities resolved after cessation of antiretroviral therapy. CONCLUSIONS: The cases described represent a degree of hepatic abnormalities that has not been reported previously in HIV-seropositive patients, and are probably an underestimate of actual incidence, since patients with possible etiologies of liver disease were excluded from the clinical history, laboratory, microbiologic, or histologic examination. The etiology of hepatic disease may be associated with antiretroviral therapy, HIV, or an unidentifiable infection, and requires further investigation. PMID- 8471201 TI - Blood transfusion practices in Mwanza Region, Tanzania. Bugando Medical Centre. AB - OBJECTIVE: To determine what proportion of blood transfusions given in Mwanza Region, Tanzania could be avoided. METHODS: A total of 1029 patients who received a blood transfusion in one of eight hospitals were analysed. Two sets of criteria for avoidable blood transfusions were determined, on the basis of a literature review. RESULTS: The following percentages of blood transfusions in five groups of patients were found to be avoidable: operated patients, 8-24%; pregnant women, 8-10%; children aged under 5 years, 31-52%; children aged 5-14 years, 23-25%; and adults, 16-25%. Overall, 23-39% of blood transfusions were avoidable. At least 75% of all avoidable blood transfusions were to children aged under 5 years. CONCLUSIONS: The largest reduction of blood transfusions can be achieved in children aged under 5 years, especially in infants aged less than 1 year. Following this study, blood transfusion prescribers drew up provisional guidelines on blood transfusions, which have been introduced in all hospitals in Mwanza Region. An evaluation study has been carried out and is being analysed. PMID- 8471202 TI - European Community Concerted Action on HIV seroprevalence among sexually transmitted disease patients in 18 European sentinel networks. The European Study Group. AB - OBJECTIVE: Monitoring HIV infection in sentinel populations of sexually transmitted disease (STD) patients in several geographical areas. This paper describes the main characteristics of the study populations and compares HIV seropositivity rates within and between networks in different subgroups: homo /bisexuals, intravenous drug users (IVDU) and non-IVDU heterosexuals. DESIGN: HIV testing is performed with informed consent in most networks. It is mandatory for STD patients in Hungary, while the English and Welsh, Scottish and French networks use unlinked anonymous testing. SETTING: Eighteen networks in 17 European countries are participating in the study. The networks usually consist of STD or dermato-venereology clinics. PATIENTS: Patients presenting at any of the clinic sites with a new episode of one or more of a selected list of 12 STD were eligible for the study. This study recorded a total of 36,827 STD episodes, registered between June 1990 and December 1991. HIV test results were known for 33,004 (89.6%) of the patients. RESULTS: HIV seropositivity rates were usually much higher for the homo-/bisexual and IVDU patients than for the non-IVDU heterosexuals. However, HIV-seropositive patients were found among non-IVDU heterosexuals in all but the Czech network. CONCLUSION: This Concerted Action has successfully launched an HIV sentinel surveillance programme among STD patients in 17 European countries using a standard methodology. PMID- 8471203 TI - HIV infection in European female sex workers: epidemiological link with use of petroleum-based lubricants. European Working Group on HIV Infection in Female Prostitutes. AB - OBJECTIVES: To assess the prevalence of and risk factors associated with HIV infection in European female sex workers, particularly sexual risk factors. DESIGN: Multicentre cross-sectional study performed in nine European countries. METHODS: Female sex workers voluntarily enrolled between September 1990 and November 1991. Face-to-face interviews were conducted in various settings (health care, prostitute organizations, outreach) to collect information on over 150 behavioural, health and sociodemographic variables. Enrollment of intravenous drug users (IVDU) was limited to a maximum of 25% of the total sample. The HIV-1 and HIV-2 antibody status of blood or saliva samples was tested using enzyme linked immunosorbent assay and confirmed by Western blot. RESULTS: Eight hundred and sixty-six (91.6%) of the 945 interviewees provided blood (n = 824) or saliva (n = 42) samples. HIV seroprevalence was 5.3% [44 HIV-1-positives and two HIV-2 positives (from Lisbon)] overall, 31.8% (35 out of 110) in IVDU and 1.5% (11 out of 756) in non-IVDU [odds ratio (OR), 31.6; P < 0.001]. Lack of condom use (P = 0.002, test for trend) and previous ulcerative sexually transmitted disease (OR, 3.6; P = 0.06) were associated (on logistic regression) with HIV infection in both IVDU and non-IVDU. Previous hepatitis B (OR, 13.8; P = 0.02) and needle sharing (OR, 4.1; P = 0.04) were associated with HIV infection in IVDU, and low education level (P = 0.02, test for trend), previous transfusion (OR, 9.1; P = 0.003), origin from sub-Saharan Africa (OR, 5.4; P = 0.05) and use of petroleum based lubricants (OR, 15.2; P = 0.001) in non-IVDU. CONCLUSIONS: HIV prevalence remains relatively low among non-IVDU prostitutes in Europe. While intravenous drug use remains the most important risk factor for HIV, petroleum-based lubricants (used by 10% of women in this study) may be a risk factor for HIV among European female sex workers; over 80% of those interviewed always used condoms with clients. PMID- 8471204 TI - HIV risk-related sexual behaviors among heterosexuals in New York City: associations with race, sex, and intravenous drug use. AB - OBJECTIVE: To investigate the relationship between heterosexual behaviors associated with HIV infection and ethnicity, sex, and intravenous drug use. METHODS: Subjects were recruited from Bellevue Hospital Center, New York City between 1986 and 1989, and interviewed about sexual behaviors and intravenous drug use. Analyses were based on 1561 black, white, or Hispanic individuals who reported having sexual contact with a member of the opposite sex. RESULTS: Twenty seven per cent of the study population were black, 43% Hispanic, and 31% white. Blacks were more likely than whites or Hispanics to have initiated sexual intercourse at an early age, and to have had a sexually transmitted disease. Sex with a female drug user was more common among white men, and contact with a prostitute more frequent among Hispanic men. Among the women, Hispanics had fewer sexual risk factors overall than whites or blacks. Use of barrier contraceptives was uniformly low across all ethnic groups. Intravenous drug use was significantly associated with sexual risk-taking. Women were more likely than men to have an intravenous drug-using (IVDU) sexual partner. CONCLUSIONS: The large prevalence of high-risk sexual practices observed in this study emphasizes the continuing need to target AIDS prevention programs at those at highest risk of heterosexually transmitted HIV: racial minorities, IVDU, and their sexual partners. PMID- 8471205 TI - Improved survival from diagnosis of AIDS in adult cases in the United Kingdom and bias due to reporting delays. AB - OBJECTIVE: To measure developments in survival patterns among United Kingdom adult AIDS cases. DESIGN: A follow-up survey of cases reported voluntarily to the national surveillance schemes was undertaken to obtain up-to-date information on vital status. METHODS: All reporting clinicians who had a current AIDS patient not known to have died whose AIDS-defining illness was diagnosed before the end of September 1990 were contacted. A total of 3984 cases were included in the analysis. RESULTS: An extra third of deaths other than those reported through routine channels were ascertained by follow-up. Median survival for patients diagnosed before and after the end of 1986 increased from 15 to 18 months for men who had sex with men presenting with Kaposi's sarcoma, from 10 to 19 months for other men who had sex with men and from 7 to 16 months for all others. Improvement in survival was greatest in the first 3 months. One-third of patients have been surviving 2 years or more. Factors observed with independent effects on improved survival are recent diagnosis, younger age and larger cumulative AIDS case load of reporting centre. HIV encephalopathy and other central nervous system symptoms may be associated with poorer survival. CONCLUSIONS: Survival patterns have been changing and generally improving. Average survival for very recent cohorts tends to be underestimated because longer survival has been observed in patients for whom there is a longer delay between AIDS diagnosis and report to the Communicable Disease Surveillance Centre. Information on mortality is improved by active follow-up. PMID- 8471206 TI - The epidemiology of AIDS in the Vellore region, southern India. AB - OBJECTIVE: To describe the epidemiology of patients with AIDS in Vellore region, Southern India. DESIGN AND METHODS: Sixty-one patients with AIDS were diagnosed and treated between July 1987 and June 1992. Information on their demographic characteristics and probable modes of acquiring HIV infection was collected at interviews with them and their spouses. RESULTS: There was a progressive increase in the number of patients seen over the 5 years. The mean ages of the 51 men and the 10 women were 33 and 29 years, respectively. Of the 44 patients from our district (population, 5 million), 28 were from Vellore town and 10 from rural areas. Forty-seven (92%) men had frequently used prostitutes. Of the women, four were prostitutes, one had had multiple sex partners and five had not had extramarital sexual contact. One man and one woman had no other risk factor except blood transfusion. Thirty-one (51%) patients had died by August 1992. CONCLUSION: The AIDS epidemic in this region is in its early ascending phase, with a doubling time of approximately 1 year. Most men with AIDS were infected by heterosexual contact with prostitutes, while some women were prostitutes themselves. Together with the male-to-female ratio of 5:1, these results suggest that the male population at risk has sex with a much smaller population of female prostitutes, constituting the major chain of transmission. HIV infection is occurring in both urban and rural populations. PMID- 8471207 TI - Disclosing HIV seropositivity to significant others. AB - OBJECTIVES: To examine gay men's patterns of self-disclosure of HIV seropositivity to friends, lovers, relatives and colleagues; to assess the effects of disclosure; and to identify reasons for not disclosing to particular individuals. DESIGN: Longitudinal questionnaire survey of gay men. METHODS: A total of 163 HIV-positive men participating in the AIDS Behavioral Research Project, a longitudinal study of San Francisco gay men, completed questionnaires about their self-disclosure patterns, health status, and psychological well being. RESULTS: HIV-positive men were most likely to disclose their status to lovers and closest gay friends. Asymptomatic men were less likely to disclose to relatives and colleagues than symptomatic men. Friends and lovers were rated as responding more helpfully than relatives and colleagues. Men who perceived their significant others as responding more helpfully were less depressed and anxious currently and 1 year later. A variety of reasons were given for not disclosing, including not wanting to worry others, fear of discrimination, fear of disrupting relationships, and emotional self-protection. CONCLUSION: While disclosure can have advantages for both HIV-positive individuals and their significant others, HIV-positive individuals must be assured that the benefits of doing so will outweigh the potential costs. PMID- 8471208 TI - p24 antigenaemia and clinical response to zidovudine therapy. PMID- 8471209 TI - Case study of zidovudine overdose. PMID- 8471210 TI - The presence or absence of gp120/gp160 bands on indeterminate western blots: predictive value for HIV seroconversion. PMID- 8471211 TI - No antibodies to granulocyte macrophage colony-stimulating factor with prolonged use in AIDS. PMID- 8471212 TI - Letrazuril therapy for cryptosporidiosis: clinical response and pharmacokinetics. PMID- 8471213 TI - The relative efficacy of oral dapsone and nebulized pentamidine as prophylaxis for Pneumocystis carinii pneumonia. PMID- 8471214 TI - Prevalence of injecting drug use provides the context for epidemiology of HIV among injecting drug users. PMID- 8471215 TI - Temporal trend of HIV infection among pregnant women in a reference hospital in Barcelona. PMID- 8471216 TI - Inheritance of parental chromosomes 15 in Angelman syndrome--implications for the family. AB - Molecular and cytogenetic studies in Angelman syndrome have demonstrated that the condition is genetically heterogeneous with a recurrence risk in certain families which may be as high as 50%. In an attempt to identify such families, cytogenetic polymorphisms of chromosome 15 have been studied in both affected and unaffected siblings of Angelman syndrome patients. The results suggest that in those cases with a cytogenetically visible 15q11q13 deletion where the recurrence risk is low, normal siblings inherit either maternal chromosome 15 homologue with impunity. By contrast, in cases where the proband does not demonstrate a cytogenetic 15q11q13 deletion, unaffected siblings tend to inherit the alternative homologue to that found in their affected siblings. These findings may have importance for genetic counseling. PMID- 8471217 TI - Autosomal recessive congenital stenosis of aqueduct of Sylvius. AB - Congenital hydrocephalus is an etiologically heterogeneous central nervous system malformation. Mendelian inheritance of stenosis of the aqueduct of Sylvius (SAS) accounts for almost 2% of all nonsyndromic forms. Among the monogenetic forms the great majority are X-linked. In this report we describe autosomal recessive transmission of SAS hydrocephalus in a high consanguinity family. PMID- 8471219 TI - Wiedemann-Beckwith syndrome and chromosomal duplication 4q/deficiency 18p. AB - In this report we present a female newborn with Wiedemann-Beckwith syndrome and duplication 4q/deficiency 18p as the result of an unbalanced paternal 4q/18p translocation: karyotype: 46,XY,t(4;18)(q34.2;p11.32). The different mechanisms resulting in prenatal overgrowth and Wiedemann-Beckwith syndrome phenotype are reviewed. The suggestion is made that contiguous gene duplications/deletions other than those located in the 11p15 region may exist. PMID- 8471218 TI - Carpo-tarsal osteolysis. Case report and review of the literature. AB - A hereditary form of multicentric osteolysis is described in an 11-year-old girl whose father is also affected. The results after corrective surgery on the foot with the Ilizarov fixator and the findings during arthroscopy of the knee are discussed. The literature is reviewed. PMID- 8471220 TI - Larsen syndrome presenting as a familial syndrome of dwarfism, distinct oldish facial appearance and bilateral clubfeet in mother and daughter. PMID- 8471221 TI - Macrocephaly and mental retardation. The unique association with short stature, spastic paraplegia and CNS malformations. AB - During a systematic clinical genetic survey of the institutionalized moderately to severely mentally retarded we had the occasion to examine two nonrelated adult patients who presented a similar MCA/MR syndrome: 1) macrocephaly (OFC > 60 cm) with high and broad forehead and contrasting relative midfacial hypoplasia; 2) short stature with small and broad hands and feet; 3) neurological symptoms of a variable degree of spastic paraplegia and severe CNS malformations on CT-scan i.e. internal hydrocephalus and Dandy-Walker variant malformation. PMID- 8471222 TI - The fragile-X phenotype. Computer assisted analysis of the dysmorphological features and discrimination from the Sotos phenotype. AB - Fragile-X and Sotos phenotypes may be difficult to distinguish. This is illustrated with a case report. Computer assisted phenotype analyses (MDDB), using the complete trait list of this patient, suggested the fragile-X diagnosis, which later was confirmed by molecular techniques. The results of corresponding phenotype analyses are summarized for 17 children with proven fragile-X, and 10 children with suggested Sotos syndrome. PMID- 8471223 TI - An unclassifiable type of spondylo-peripheral epiphyseal dysplasia associated with 21 trisomy. AB - We present an unusual type of skeletal dysplasia in a 6 1/2 year-old female child with Down syndrome due to classical 21 trisomy. Differential diagnosis with the pseudoachrondroplastic forms of spondyloepiphyseal dysplasia shows that the epiphyseal changes in the present patient are unique and do not allow to classify the skeletal changes of the present patient in this group of disorders. PMID- 8471224 TI - The association of hemifacial microsomia, homolateral micro/anophthalmos, hemihypotrophy, dental anomalies, submucous cleft palate, CNS malformations and hypopigmented skin lesions following Blaschko's lines in two unrelated female patients. Further evidence for a lethal mutation surviving in mosaic form in "hypomelanosis of Ito". PMID- 8471225 TI - Ptosis, coloboma, hypertelorism and mental retardation. PMID- 8471226 TI - Intelligence, behaviour and psychosocial development in Turner syndrome. A cross sectional study of 50 pre-adolescent and adolescent girls (4-20 years). AB - In this paper we report the findings and data on a cross-sectional study of 50 pre-adolescent and adolescent girls with Turner syndrome. We confirm the presence of a typical cognitive profile in the different age groups with normal verbal intelligence contrasting with lower results on performal IQ subtests, related to relative weaknesses on visuospatial subtests i.e. "Block Design" and "Object Assembly". 5% of the girls with a "classical" Turner syndrome karyotype (i.e. 2/40) were mentally retarded versus 30% (i.e. 3/10) in the group with "rare" karyotypic anomalies. We noted a positive influence of hormonal therapy on the visuospatial functioning. No evidence was found for a high risk for behavioural problems. Hyperactive behaviour was seen in the youngest patients contrasting with a tendency to hypoactivity around the age of normal puberty. Problems in social development were noted from the age of primary school on resulting in social immaturity and even isolation. A proposal for guidance of Turner girls during the different developmental periods is given. PMID- 8471227 TI - Kabuki make-up (Niikawa-Kuroki) syndrome in a girl presenting with vitiligo vulgaris, cleft palate, somatic and psychomotor retardation and facial dysmorphism. PMID- 8471228 TI - Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients. AB - The correction of anemia in end stage renal disease with recombinant human erythropoietin (rHuEPO) is associated with hypertension in about a third of hemodialysis patients. In the present study, we investigated the role of endothelin (ET-1) on rHuEPO associated hypertension and the effect of the rHuEPO administration route on plasma ET-1 levels. We studied 50 stable chronic hemodialysis patients who were divided into three groups: 26 patients received rHuEPO intravenously (IV) and 21 subcutaneously (SC). The control group was nine patients who were treated with nandrolone decanoate (ND). Prehemodialysis ET-1 plasma levels were correlated with mean arterial pressure (MAP), hematocrit (Hct), time on dialysis, and rHuEPO doses. The antihypertensive therapeutic index (ATI) was used to determine the changes in blood pressure medication intake. We observed that the ET-1 levels were significantly higher in the IV group (19.3 +/- 2) than the SC (5.0 +/- 0.6) or ND groups (3.6 +/- 0.4 pg/mL) (P < 0.001, IV v SC or ND). After IV rHuEPO treatment, there were increases in both MAP (pre- v post rHuEPO, P < .001) and in ATI (pre- v post-rHuEPO, P < .001). In the SC group, the increases in MAP and ATI were not significant. Only the IV group showed a significant correlation between MAP and ET-1 levels (r = .05, P = .02). To accomplish the same Hct, the IV group received higher rHuEPO doses than those of the SC (180 +/- 15 v 87 +/- 12 U/kg/week) (P < .001). No significant correlations were found between the plasma ET-1 levels and Hct, time on dialysis and rHuEPO doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471229 TI - Long-term effects of a converting enzyme inhibitor and a calcium channel blocker on urinary albumin excretion in patients with essential hypertension. AB - Microalbuminuria in patients with essential hypertension is associated with increased incidence of cardiovascular morbidity and mortality. Reduction of urinary albumin excretion (UAE) with therapy could reduce cardiovascular events. The long-term effect of commonly used antihypertensive agents on UAE has not been properly investigated. In the present study, we have prospectively studied the effects of therapy for 24 months with a converting enzyme inhibitor, enalapril, or a calcium channel blocker, nicardipine, on UAE in 40 patients with essential hypertension and microalbuminuria. Enalapril and nicardipine were equally effective in reducing arterial pressure. However, enalapril decreased UAE from 77.1 +/- 10.4 to 30.4 +/- 7.9 mg/24 h after 1 year, and to 24.7 +/- 4.8 (P < .01) after 2 years of therapy. UAE however, did not change in patients treated with nicardipine (from 65.2 +/- 12 to 73 +/- 14 after 1 year, and to 52.7 +/- 21 mg/24 h after 2 years of therapy). The impact of reducing UAE on overall cardiovascular morbidity and mortality and on future progression of renal failure in patients with essential hypertension remains to be established. PMID- 8471230 TI - Ambulatory blood pressure monitoring in offspring of hypertensive patients. Relation to left ventricular structure and function. AB - The relation between 24-h ambulatory blood pressure monitoring and echocardiographic left ventricular (LV) anatomy and function was examined in 30 young, normotensive offspring (16 men, 14 women) of hypertensive, parents and in 20 offspring (12 men, 8 women) of normotensive parents, comparable for age, clinical blood pressure, and gender. Offspring of hypertensive subjects exhibited higher body mass index (P < .01), relative wall thickness, and LV mass/height (both P < .001). No significant difference was found in LV chamber dimensions and in either systolic or diastolic function. The 24-h systolic and diastolic blood pressures were higher in offspring of hypertensive subjects than in controls (P < .001 and P < .0001, respectively), as was the coefficient of variation of 24 h systolic blood pressure (P < .01). In pooled groups, LV mass was positively related to daytime systolic blood pressure (r = 0.48), daytime diastolic blood pressure (r = 0.47) (both P < .001), and the coefficient of variation of 24 h diastolic blood pressure (r = 0.37, P < .01). In a multiple regression model, including as variables, body mass index, daytime systolic and diastolic blood pressures, male gender, and family history of hypertension were the major independent predictors of LV mass (both P < .0001), with an additional contribution of the coefficient of variation of 24 h diastolic blood pressure (P < .05). We conclude that male gender and a family history of hypertension are stronger determinants of early changes in cardiac structure than hemodynamic load in a group of young, normotensive adults. PMID- 8471231 TI - Combined effects of dietary fish oil and sodium restriction on blood pressure in enalapril-treated hypertensive rats. AB - Sodium restriction and fish oil supplementation are effective dietary measures for preventing or treating mild hypertension. However, their usefulness as an adjunct to drug treatment of hypertension requires further evaluation. In the present study, we examined the influence of dietary sodium and fish oil on the antihypertensive effect of the angiotensin converting enzyme (ACE) inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP). Rats were fed experimental diets containing fish oil or olive oil (5% w/w) and low (0.04% w/w) or normal (0.23% w/w) sodium from 1 to 4 months of age. Tail-cuff blood pressure (BP) rose by 8.4 and 4.3 mm Hg/week, respectively, in untreated and enalapril treated (2.5 mg/kg/day, orally) rats fed the olive oil/normal sodium diet. Feeding fish oil further reduced the rise in enalapril-treated rats to 2.8 mm Hg/week. When sodium intake was also restricted, the BP rise was almost prevented (1.1 mm Hg/week). In older rats with established hypertension, the low sodium/fish oil diet also potentiated the blood pressure reduction by enalapril (tail-cuff BP fell by 61 mm Hg compared to 25 mm Hg with enalapril alone). These observations were confirmed by direct BP recording in conscious rats following the implantation of aortic catheters. Factorial analysis revealed a highly significant antihypertensive effect of fish oil in both young and adult SHRSP receiving enalapril, and a further interactive effect of dietary sodium restriction with fish oil feeding in young rats. The antihypertensive effects of the dietary interventions were associated with further reductions of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471232 TI - Diurnal blood pressure variability and physical activity measured electronically and by diary. AB - In order for 24 h ambulatory blood pressure monitoring (ABPM) to be useful in clinical decision making, it is necessary to quantify ambient physical activity and to develop appropriate norms of ambulatory pressure for different levels of activity. The present study has compared the predictive value of physical activity determined by an electronic activity monitor or a written diary, for concomitantly recorded blood pressure during ABPM in healthy normotensive subjects. Each subject wore four activity monitors, on the right and left wrists, on the left ankle and at the waist, respectively. Linear regression analysis was performed for each subject to determine the correlation between ABPM data (systolic and diastolic blood pressure and heart rate) and activity data (obtained from diaries and the four monitors). Significant differences in the degree of correlation were found for both the location of the activity monitor and the time (1/2, 2, 5, 10, 15, and 30 min preceding blood pressure measurement) over which activity was averaged (P < .05 by two-way analysis of variance). The best correlation was obtained with the activity monitor worn on the dominant wrist, and when activity was averaged over 2 to 10 min preceding blood pressure determination, accounting for 18 to 69% (mean 36 +/- 5%) of systolic blood pressure variation. Diaries performed similarly in these well-motivated subjects. It is concluded that because of the significant interaction between activity and blood pressure, ABPM data should be interpreted only in the light of concomitant activity data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471233 TI - Identification and purification of parathyroid hypertensive factor from organ culture of parathyroid glands from spontaneously hypertensive rats. AB - Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor isolated from the plasma of spontaneously hypertensive rats (SHR). Recent studies have suggested that the primary origin of PHF is the parathyroid gland (PG). In the present investigation, PG from spontaneously hypertensive rats (SHR), as well as from normotensive rats, were isolated and maintained in culture. The PG from SHR, but not normotensive rats, released PHF into the culture medium. Omission of calcium from the culture medium stimulated the release of PHF. For purification of PHF, parathyroid gland culture medium (PGCM) was first dialyzed at 1000 mwco, and then ultrafiltered at 5000 molecular weight cut-off (mwco). PHF activity was retained in the fraction that was greater than 1000 daltons and less than 5000 daltons. Dialyzed and filtered SHR PGCM was fractionated by molecular exclusion HPLC. Biologically active PHF was collected in a discrete region. The biologically active molecular exclusion fraction was subsequently fractionated by reverse-phase HPLC (C-8). PHF was collected in a single discrete peak, which did not occur in culture medium prepared from normotensive PG in a similar manner. This biologically active peak occurred in the same position on molecular exclusion and reverse-phase HPLC as PHF purified from SHR plasma using similar procedures. Incubation of PGCM with trypsin inactivates the biological activity of PHF. The UV spectrum of PGCM PHF is identical to that obtained from purified plasma PHF. These results are consistent with the presence of a peptide moiety in PHF, and support the parathyroid origin of plasma PHF. PMID- 8471234 TI - Noninvasive ambulatory 24 h blood pressures and basal blood pressures predict development of sustained hypertension from a borderline state. AB - A sample of 143 male borderline hypertensives aged 35 to 45, screened from a population cohort, were subjected to psychological stress, static work, and ambulatory 24 h blood pressure (BP) monitoring to assess the predictive power of BP reactivity in the development of established hypertension. After 1 year, a follow-up showed that 21 subjects (14.7%) had developed established hypertension (causal diastolic (D) BP > or = 95 mm Hg), 25 subjects (15.7%) had become normotensive (causal DBP < 85 mm Hg), and 97 (67.8%) remained within the borderline range (causal DBP 85 to 94 mm Hg). Those who developed established hypertension had considerably higher initial basal resting blood pressures than those who remained borderline: systolic (S) BP 134.2 +/- 12.5 v 127.6 +/- 10.7 mm Hg, P < .05 and DBP 86.8 +/- 7.9 v 80.4 +/- 7.0 mm Hg, P < .01. They had also somewhat higher BP values during mental arithmetic exercises and hand-grip work (peak DBP 101.1 +/- 8.8 v 96.8 +/- 8.7 mm Hg, P < .05, and 131.4 +/- 14.8 v 123.5 +/- 12.9 mm Hg, P < .05, respectively). Those subjects who developed established hypertension had significantly higher 24 h mean blood pressures than those who remained borderline (24 h SBP 133.3 +/- 11.4 v 126.0 +/- 10.1 mm Hg, P < .01, and DBP 84.7 +/- 5.7 v 81.6 +/- 6.8 mm Hg, P < .05). This difference was attributed mainly to the differences found during daytime (07:00 to 19:00) hours but was also found to be nominally dependent upon those found during nighttime (01:00 to 07:00) hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471235 TI - Assessment of left ventricular hypertrophy in patients with essential hypertension. A rational basis for the electrocardiogram. AB - There is a large body of evidence that the electrocardiogram (ECG) is insensitive in the recognition of left ventricular hypertrophy (LVH), in comparison with the echocardiogram; however, its specificity is high. In this study we further analyzed the performance of the ECG in detecting LVH in 200 consecutive patients (124 men and 76 women, mean age 50.9 years) with mild to moderate essential hypertension, using echocardiographically determined left ventricular mass (LVM) as the standard for comparison. To test the hypothesis that, owing to the high number of true positive findings, the ECG may still be useful for clinical purposes by selecting subsets of hypertensives with higher degrees of LVH, we compared the mean values of LVM index corresponding to either positive (true positive) or negative (false negative) electrocardiographic signs of LVH. In this study 69 patients (34.5%) had echocardiographic LVH, as defined by a LVM index exceeding 125 g/m2 for men and 112 g/m2 for women. Almost all criteria demonstrated high levels of specificity (> or = 89%). In the whole group the Lewis index ((RI - RIII)+(SIII - SI) > or = 17 mm) showed a slight superiority in diagnosing LVH (sensitivity = 43%) in comparison to the remaining criteria; the confidence intervals estimate of sensitivities confirmed such diagnostic superiority only with respect to those criteria with a sensitivity < or = 17%. However, the use of McNemar's test to compare sensitivities of all electrocardiographic criteria at matched specificities (> or = 95%) did not show significant differences (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471236 TI - Increased left ventricular mass in normotensive diabetic patients with autonomic neuropathy. AB - The possible relationship between diabetic autonomic neuropathy, circadian blood pressure changes, and echocardiographic parameters was investigated in 27 normotensive diabetic patients (10 with and 17 without autonomic neuropathy) who underwent 24 h noninvasive ambulatory blood pressure monitoring and M-mode echocardiographic recording. The two groups were comparable for age, sex, duration of diabetes, body mass index, and metabolic control. There were no significant differences in 24 h average and diurnal values of systolic, diastolic, or mean blood pressure. The percent changes from day to night of systolic, diastolic, and mean blood pressures were significantly lower in diabetics with neuropathy than in those without (P < .04 or less). Increased left ventricular mass index (LVMI) (135.4 +/- 10.2 v 102.9 +/- 6.3; P < .005), septal wall thickness, and posterior wall width were observed in neuropathic patients. Fractional shortening, peak velocity of early left ventricular filling (E), peak velocity of late ventricular filling (A), and their ratio (E/A) were similar in the two groups. The increased LVMI we observed may represent a possible link between diabetic autonomic neuropathy, nocturnal blood pressure levels, and higher cardiovascular mortality rate. PMID- 8471237 TI - Polyol pathway-related skeletal muscle contractile and morphological abnormalities in diabetic rats. AB - This study examined the effect of inhibition of aldose reductase, the first enzyme in the polyol pathway, on fast and slow twitch skeletal muscle morphology and function in streptozotocin-induced diabetes in rats. There was a preventative investigation with diabetes duration of 4 months, and a reversal investigation where treatment was given for 2 months following an untreated period of 2 months. For slow twitch soleus muscle, contractions were prolonged by diabetes, and this was partially prevented but not reversed by treatment. Relaxation was profoundly slowed, and both prevention and reversal ameliorated the changes. Diabetes had minimal effects on tension production for soleus. However, for fast twitch extensor digitorum longus, although there was little effect on speed-related contractile parameters, tetanic tension production was progressively reduced with diabetes duration. This effect was antagonized by treatment. Soleus fatigue resistance was markedly reduced by diabetes, but restored to normal by treatment. There was a reduction in oxidative enzyme staining (succinic dehydrogenase), and capillary-fibre ratio, both of which were ameliorated by aldose reductase inhibition. Mean soleus fibre area was reduced after 4 months of diabetes, and this was prevented but not reversed by treatment. Fibre area was also reduced in extensor digitorum longus, particularly for fast glycolytic fibres. There was a small amelioration with treatment. It is concluded that enhanced polyol pathway activity makes a contribution to diabetic myopathy, and that aldose reductase inhibitors can prevent this by actions on muscle fibres and their vascular supply. PMID- 8471238 TI - Effects of D-glucose, L-glucose and D-mannitol on renal calcium handling and general renal function in the rat. AB - Standard renal clearance techniques were used to compare the effects of D glucose, L-glucose and D-mannitol on renal calcium handling and general renal function in the anaesthetized rat. A significant (P < 0.01) calciuresis was seen in animals infused with D-glucose. This resulted from a decreased tubular reabsorption of calcium. A similar response was not seen with L-glucose or D mannitol. The contrasting actions of the three sugars on tubular calcium transport may relate to their different transport characteristics, since only D glucose is actively reabsorbed. Responses of the three sugars also differed with respect to fractional fluid and sodium reabsorption which were significantly (P < 0.001) lower in animals infused with L-glucose and D-mannitol, and plasma insulin concentrations which were significantly (P < 0.01) elevated only in the D-glucose group. An unexpected finding was a highly significant (P < 0.001) and progressive fall in glomerular filtration rate (GFR) in animals infused with L-glucose. The reasons for this are not known. PMID- 8471239 TI - Renal micropuncture study of the effects of D-glucose tubular calcium handling in the anaesthetized rat. AB - Tracer microinjection studies were used to grossly locate the nephron site of altered calcium transport following D-glucose loading. Superficial proximal and distal nephrons were injected with a solution containing 45Ca and either D glucose or L-glucose (as control). Tubule calcium transport was assessed from the recovery of radioactivity in the final urine. 45Ca recoveries from early proximal microinjections were comparable in the two groups (2.63 +/- 0.68 vs. 3.70 +/- 1.19%). However, 45Ca recoveries from late proximal microinjections were significantly higher than D-glucose was included in the injectate (7.39 +/- 1.34 vs. 2.83 +/- 0.67%, P < 0.05). 45Ca recoveries from distal microinjections were also significantly higher in the D-glucose group (87.6 +/- 2.43 vs. 71.0 +/- 2.92%, P < 0.001). These data suggest that the effects of D-glucose on renal calcium handling are mediated at the level of the distal tubule, thick ascending limb of the loop of Henle and/or pars recta. The precise mechanisms involved are not known. PMID- 8471240 TI - Acute and chronic effects of pancreatic glucagon on sugar transport across the brush-border and basolateral membranes of rat jejunal enterocytes. AB - Preparations of isolated rat jejunal enterocyte and brush-border and basolateral membrane vesicles have been used to study the effects of a 15 min exposure of upper and mid-villus enterocytes to pancreatic glucagon on the initial, unidirectional phlorhizin-sensitive (brush border) transport of galactose and phlorhizin-insensitive (basolateral) movement of the sugar. These acute effects of glucagon have been compared with responses following treatment of animals for 1 or 3 days with the hormone. Incubation of cells with glucagon significantly stimulated phlorhizin-sensitive uptake by 42 and 64% for upper and mid-villus cells, respectively. Glucagon, however, was without effect on phlorhizin insensitive galactose uptake. This differential action of the hormone at the two cellular loci was confirmed by uptake data obtained using purified brush-border and basolateral membrane vesicles prepared from isolated cells. In contrast to the acute challenge with glucagon, treatment of animals for 3 days with the hormone significantly increased both phlorizin-sensitive (upper villus +31%, mid villus +74%) and phlorizin-insensitive (upper villus +42%, mid-villus +53%) galactose uptake. Glucagon exposure of exposure of isolated cells from 3 days treated animals was without further effect on galactose uptake at the two membrane loci. These data represent the first evidence for a direct action of pancreatic glucagon on enterocyte sugar transport. Thus the hormone is likely to be important in the physiological control of sugar absorption in addition to its possible role in the modulation of transport during starvation and diabetes mellitus, conditions characterized by hyperglucanonaemia and enhanced intestinal sugar transport. PMID- 8471241 TI - The short-term synthesis and infant-regulated removal of milk in lactating women. AB - We studied how short-term milk synthesis responds to milk removal by observing breast volume before and after each breastfeed over 24 h periods within the homes of seven lactating mothers, using the Computerized Breast Measurement system. Short-term rates of milk synthesis varied markedly between the breasts of individual mothers, varied markedly between interfeed intervals for individual breasts and, for six of the thirteen breasts studied, were positively related to the degree to which the breast was emptied (r2 ranging from 0.32 to 0.95). In addition, the infants rarely emptied the breasts of available milk (mean +/- S.D. of degree of emptying postfeed = 76 +/- 20%, n = 147) and, within women, storage capacity of a breast was related to the demand for milk from that breast (r2 = 0.91, P < 0.0001). It was concluded that the infants were self-regulating their milk intake. Furthermore, the storage capacity of the breast, variations in the short-term rates of milk synthesis and responsiveness of milk synthesis to the degree of breast emptying provided mechanisms whereby maternal milk supply could be directly linked to infant demand. Our findings are discussed with reference to the autocrine control of milk synthesis. PMID- 8471242 TI - The regulation of intracellular Mg2+ in guinea-pig heart, studied with Mg(2+) selective microelectrodes and fluorochromes. AB - Because of the reported presence of a Na(+)-Mg2+ exchanger in guinea-pig but not in ferret myocardium, the Mg2+ extrusion mechanism in guinea-pig myocardium has been reinvestigated using Mg(2+)- and Na(+)- selective microelectrodes and the fluorochromes mag-fura-2 and -5. The mean [Mg2+]i measured with microelectrodes in trabeculae or papillary muscles was 0.72 mmol/l (n = 22, thirteen experiments; range 0.42-1.23 mmol/l). Increasing [Mg2+]o from 0.5 mmol/l to either 10.5 or 20 mmol/l caused small increases in [Mg2+]i. Decreasing [Na+]o by 50% had no effect on the [Mg2+]i and there was no change in [Na+]i on increasing [Mg2+]o from 0.5 to 10.5 mmol/l. Varying pHo or changing pHi with NH4Cl did not influence the [Mg2+]i. In vitro calibration of mag-fura-2 and -5 using the ratio method gave values for K'd (experimentally determined dissociation constant) of 22.2 +/- 2.7 (mean +/- S.D., n = 7) and 25.7 +/- 1.3 (n = 4) mmol/l respectively. Mag-fura-2 reacted to physiological concentrations of Ca2+ and mag-fura-5 to changes in pH. In isolated myocytes, Na+ removal gave an apparent increase of [Mg2+]i with mag fura-2 but not with mag-fura-5. However, when the pHi was altered with NH4Cl mag fura-5 showed an apparent decrease in [Mg2+]i on application and an apparent increase on removal, with a time course similar to the pHi changes. It is concluded that Mg2+ extrusion in guinea-pig myocardium is not via a Na(+)-Mg2+ exchanger. The use of mag-fura-2 and -5 are limited in their application because of Ca2+ and H+ sensitivity respectively. PMID- 8471243 TI - Short-term oscillations of aortic core temperature and thermogenic organ blood flow in the rat. AB - Core and organ temperatures in the rat have been found to be subject to regular periodic oscillations (with a frequency of ca 12 cycles per day, i.e. 143 mu Hz) within set limits, by using a chronic thermocouple implant procedure. These cycles consisted of consecutive warming (the temperature increased steadily) and cooling periods (the temperature decreased regularly). There were sustained temperature differences between several tissues and that of the aortic blood (core temperature), higher for brown adipose tissue, kidney and liver, and lower for muscle, white adipose tissue and skin. Organ blood flows and cardiac output were measured by a radioactive microsphere retention method applied to unanaesthetized rats. Blood flow measurements were done on unaware rats (see Methods), during either the warming or cooling phases. During the warming phases, there was a higher blood flow across the brown adipose tissue, kidney and skin, with a cardiac output about twice that found in the cooling periods. The haemodynamic changes observed, as well as the organ temperature differences observed with respect to the blood, suggest that periodic changes in blood flow are an essential part of the operation of the thermogenic system. PMID- 8471245 TI - Endometrial expression of progesterone receptor and uteroglobin genes during early pregnancy in the rabbit. AB - The progesterone receptor (PR) plays a pivotal role in the maturation process of the secretory endometrium, implantation and maintenance of pregnancy in rabbits. To determine the dynamics of PR gene expression and its physiological significance, the endometrial expression of PR and PR mRNA were evaluated and compared with the expression of the progesterone-regulated uteroglobin (UG) gene during 0-5 days post-coitus in rabbits. The results of immunoblot experiments indicated the presence of PR in endometrial cell extracts from days 1-4 of pregnancy with maximum PR immunostaining on day 2, followed by a marked diminution until its complete disappearance on day 5. When endometrial PR mRNA content was assessed by Northern blots, the results were similar to those of PR immunostaining, with maximal concentrations on the second day after mating. However, PR mRNA levels were still high on day 3, despite the concomitant decrease in immunostainable PR. Endometrial UG gene expression, on the other hand, exhibited a different time sequence. Thus, the UG content in uterine flushings progressively increased from day 3 after mating, reaching maximal levels on the fifth day. The endometrial UG mRNA content presented a similar profile, as its maximum concentration occurred on days 4-5. The overall results indicate that endometrial PR is down-regulated at both the mRNA and protein levels, possibly by endogenous progesterone during early pregnancy. The striking observation that maximal expression of endometrial UG gene products occurred when PR and its mRNA are no longer detectable suggests an important role for this progesterone-binding uterine protein during the preimplantation period. PMID- 8471244 TI - Acrogranin, an acrosomal cysteine-rich glycoprotein, is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells. AB - Spermatogenesis is a unique system of differentiation involving cellular remodeling and the biogenesis of sperm-specific organelles. To study the biogenesis of one such organelle, the acrosome, we have been examining the gene expression, biosynthesis, and targeting of specific acrosomal proteins during mammalian spermatogenesis. An acrosomal marker that we recently purified and began characterizing is acrogranin, a 67,000-molecular-weight glycoprotein originally isolated from guinea pig testes. This glycoprotein is detected in pachytene spermatocytes and is found later in the acrosomes of developing spermatids and sperm. Immunoblotting of several tissues and immunofluorescent localization in frozen sections of guinea pig testes suggested that acrogranin was a germ cell-specific glycoprotein that was expressed meiotically and post meiotically. However, Northern blot analysis demonstrated that the mRNA for acrogranin was ubiquitously expressed in all guinea pig and mouse tissues examined. Furthermore, the primary structures of guinea pig and mouse acrogranins, deduced from the cDNA sequences, reveal that this glycoprotein is a cysteine-rich molecule with a motif that is tandemly repeated seven times, very similar to that of the human epithelin/granulin precursor. We conclude that guinea pig and mouse acrogranins are homologues of the precursor of the human and rat epithelin/granulin peptides previously demonstrated to have growth-modulating properties. PMID- 8471246 TI - Alanine and leucine transport in unfertilized pig oocytes and early blastocysts. AB - Amino acid transport is facilitated by specific transporters within the plasma membrane of the cell. In mouse oocytes and cleavage-stage conceptus Na(+) dependent L-alanine and L-leucine transport are nearly undetectable. Sodium dependent transport via system B0,+ in the mouse conceptus increases greatly between the 8-cell and blastocyst stages. By contrast, data presented here for the pig show that L-alanine and L-leucine transport is mainly Na(+)-dependent in the oocyte; this Na(+)-dependent component of transport becomes undetectable by the blastocyst stage. The Na(+)-dependent component of transport in oocytes is inhibited by BCH (2-aminoendo-bicyclo[2.2.1] hexane-2-carboxylic acid) and L lysine and thus could be a form of system B0,+. In both oocytes and blastocysts Na(+)-independent L-leucine transport is inhibited by BCH, which is consistent with the presence of system L. The dramatic decrease in Na(+)-dependent amino acid transport activity could occur in pig conceptuses in association with the onset of RNA synthesis during the 4-cell stage. Regardless of the precise time during development at which it occurs, however, this dramatic, developmentally regulated decrease in Na(+)-dependent alanine and leucine transport activity contrasts sharply with the large increase in Na(+)-dependent system B0,+ activity that occurs during preimplantation development of murine conceptuses. Elucidation of the molecular mechanisms by which these changes occur should contribute to an understanding of regulation of gene expression during early development. PMID- 8471247 TI - Mucin-like glycoproteins in the equine embryonic capsule. AB - The equine embryonic capsule replaces the zona pellucida and envelopes the conceptus during the second and third weeks of pregnancy. Although this capsule was described more than 100 years ago, its molecular structure has not been characterized. Here we present evidence that the glycoprotein(s) of the equine capsule resembles those of the mucin glycoprotein family. The resistance of the capsule to chemical and enzymatic solubilization was confirmed, and, as in mucins, protein constituted only 35-40% of its total dry mass. Determination of the sugar composition of the capsule using colorimetric assays and high performance anion-exchange chromatography also showed it to have mucin-like characteristics. Gal, GalNAc, sulfated sugars, and sialic acid make up a high proportion of the capsular carbohydrate, while GlcNAc, Glc, and Man are minor components. These findings were verified using lectin histochemical staining of frozen sections of conceptuses. The results of amino acid analysis were also consistent with the proposal that the capsular glycoproteins belong to the mucin family. Removal of the covalently bound carbohydrate by beta-elimination under reducing conditions demonstrated that the capsule is O-glycosylated mainly on threonine residues. Affinity chromatography on jacalin-agarose confirmed that, like mucins, the capsular glycoproteins are heavily O-glycosylated. SDS-PAGE analysis revealed a prominent 21-kDa band, specific to the capsule, in preparations solubilized by trypsin but not by other proteases. Characterization of its constituent glycoprotein(s) should be helpful in elucidating the role of the capsule (and analogous blastocyst coverings in other species) during early pregnancy. PMID- 8471248 TI - Successful vitrification of bovine blastocysts, derived by in vitro maturation and fertilization. AB - Bovine blastocysts were produced through maturation, fertilization, and development in vitro. For vitrification, solutions designated EFS, GFS, and PFS were prepared; these were 40% ethylene glycol, 40% glycerol, and 40% propylene glycol, respectively, diluted in modified phosphate-buffered saline (PBS) containing 30% Ficoll + 0.5 M sucrose. The embryos were exposed to the solutions in one step at room temperature, kept in the solutions for various times, vitrified in liquid nitrogen, and warmed rapidly. When the embryos were vitrified in EFS solution after 1 or 2 min exposure, the postwarming survival rate, assessed by the reexpansion of the blastocoel, was 74-77%. However, when the exposure time was extended to 3 min or longer, this rate dropped to 7-0%. This reduction was attributed to the toxicity of ethylene glycol. Of the embryos vitrified in GFS solution, 53% survived when they were cooled after 1 min exposure; as the duration of the exposure increased, the survival rate increased, reaching a peak (72%) at 4 min. The rate then decreased gradually with exposure time. In PFS solution, embryos surviving after vitrification were recovered only with 1 min exposure (33%), reflecting the high toxicity of propylene glycol. After vitrification in EFS or GFS solution, two embryos were nonsurgically transferred into each of 14 recipient animals. Of the 14 recipients, ten (71%) became pregnant; two resulted in early stillbirths, four recipients delivered twins (four alive and four stillborn), and two delivered single live calves, demonstrating the effectiveness of this simple vitrification method for the cryopreservation of in-vitro-produced bovine blastocysts. PMID- 8471249 TI - The cleavage rate of digynic triploid mouse embryos during the preimplantation period. AB - Triploidy is a lethal condition in mammals, with most dying at some stage between implantation and term. In humans, however, a very small proportion of triploids are liveborn but display a wide range of congenital abnormalities. In particular, the placentas of human diandric triploid embryos consistently display "partial" hydatidiform molar degeneration, while those of digynic triploids generally do not show these histopathological features. In mice, the postimplantation development of diandric and digynic triploid embryos also differs. While both classes are capable of developing to the forelimb bud stage, no specific degenerative features of their placentas have been reported. Diandric triploid mouse embryos are morphologically normal while digynic triploid mouse embryos consistently display neural tube and occasionally cardiac abnormalities. Previously it was shown that the preimplantation development of micromanipulated diandric triploid mouse embryos was similar to developmentally matched diploid control embryos. In this study, the preimplantation development of micromanipulated digynic triploid mouse embryos is analysed and compared with that of diandric triploid mouse embryos in order to determine whether there is any difference in cleavage rate between these two classes of triploids. Standard micromanipulatory procedures were used to insert a female or a male pronucleus into a recipient diploid 1-cell stage embryo. The karyoplast was fused to the cytoplasm of the embryo by electrofusion. These tripronucleate 1-cell stage embryos were then transferred to pseudopregnant recipients and, at specific times after the HCG injection to induce ovulation, the embryos were recovered and total cell counts made. These results were plotted and regression lines drawn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471250 TI - Human sperm-egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor. AB - An antiserum, designated R4 and raised against denatured hamster acrosomes, was shown to localize specifically to the acrosomal region of hamster, rat, mouse, and human spermatozoa, and to inhibit both hamster and human sperm-oocyte binding in vitro. Following screening of a human testis lambda gt11 cDNA expression library with the antiserum R4, a series of cDNA clones were isolated. One (cDNA 134) was selected based on the ability of the beta-galactosidase fusion protein to inhibit human and hamster sperm-zona binding in vitro. The fusion protein was also shown to inhibit the penetration of zona-free hamster oocytes by human spermatozoa. Sequence analysis revealed that cDNA 134 coded for a portion of a serine protease inhibitor (serpin) closely related to plasma Protein C inhibitor. Sequencing of an additional cDNA clone (261) and Northern blot analysis confirmed that a Protein C inhibitor-like mRNA is synthesised in the human testis. Affinity purified anti-134 antibody specifically localized to the acrosomal region of both hamster and human sperm. Synthetic peptides corresponding to the conserved core region responsible for the interaction of the serpin with its cognate protease also blocked human sperm-zona binding in vitro. The results suggest that this acrosomally located inhibitor plays an important role in the series of binding events that results in human fertilization. PMID- 8471251 TI - Incomplete development of human spermatozoa is associated with increased creatine phosphokinase concentration and abnormal head morphology. AB - Our previous creatine phosphokinase (CK) activity studies in human sperm revealed differences among men and among sperm populations within the same specimen. Samples with low sperm concentrations, high incidence of abnormal sperm morphology, and diminished fertility had higher per sperm CK activity. In the present work, we demonstrated, with 14C-FDNB covalent CK active site modification and with direct CK immunocytochemistry, that the higher CK activity is related to an increased content of CK and of other proteins in sperm. Also, sperm heads with higher CK content were significantly larger and rounder and showed a higher incidence of amorph configuration. We suggest that these biochemical and morphological irregularities are related and are due to a failure of spermatogenesis, more specifically, to a higher retention of cytoplasm, which in normal sperm development is lost to the Sertoli cells as residual bodies. Thus higher CK activity and larger or irregular head size in human sperm signify cellular immaturity and a failure to complete spermatogenesis. PMID- 8471252 TI - The incidence of aneuploidy after single pulse electroactivation of mouse oocytes. AB - A brief electric pulse often produces a high rate of activation of recently ovulated oocytes. Some other efficient parthenogenetic stimuli, such as alcohol, however, disrupt the spindle apparatus and increase the incidence of aneuploidy. In this paper, we have determined whether electroactivation per se increases the incidence of chromosomal segregation errors in haploid parthenogenones as evidenced at first cleavage mitosis. Superovulated F1 hybrid female mice were killed at 15.5, 18.5, 22.5, and 25 h after the HCG injection. Batches of 10-12 cumulus-denuded oocytes were transferred to an electroactivation chamber containing mannitol which was connected to a high voltage pulse stimulator and the pulse was triggered once. A high proportion of oocytes activated following this treatment, but only the single-pronuclear haploid parthenogenones were incubated overnight in medium containing colcemid, to determine the incidence of aneuploidy as evidenced at first cleavage mitosis. "Sham" electroactivation groups were also examined for evidence of activation and aneuploidy as described above. In these cases, cumulus-denuded oocytes were put through the electroactivation chamber but the pulse was not triggered. A further group of oocytes was studied to determine the effect of handling and exposure to hyaluronidase on activation frequency and parthenogenetic pathways. Finally, the spontaneous rate of aneuploidy was examined in fertilised embryos of F1 hybrid female mice x Rb(1.3)1Bnr male mice at first cleavage mitosis. The results show that single pulse electroactivation does not increase the level of aneuploidy in single-pronuclear parthenogenous compared to the "sham" group or the spontaneous rate observed in 1-cell fertilised embryos, nor does aneuploidy appear to increase with postovulatory age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471253 TI - Simultaneous detection of X- and Y-bearing human sperm by double fluorescence in situ hybridization. AB - Double fluorescence in situ hybridization (FISH) was used to detect sex chromosomes in decondensed human sperm nuclei. Biotinylated X chromosome specific (TRX) and digoxigenin-labeled Y chromosome specific (HRY) probes were simultaneously hybridized to sperm preparations from 12 normal healthy donors. After the hybridization, the probes were detected immunocytochemically, using two different and independent affinity systems. Ninety-six percent of the 12,636 sperm showed fluorescent labeling, of which 47.4% were haploid X and 46.8% were haploid Y. A frequency of 0.46% of XX-bearing sperm (0.28% disomic, 0.18% diploid) and 0.38% YY-bearing sperm (0.21% disomic, 0.17% diploid) was found. The overall proportions of X- and Y-bearing sperm in the ejaculates were 47.9% and 47.2%, respectively, which was not significantly different from the expected 50:50 ratio. In addition 0.21% of cells appeared to be haploid XY-bearing sperm, 0.62% were diploid XY-bearing cells, and 0.05% of cells were considered to be tetraploid cells. The application of double FISH to human sperm using X chromosome and Y-chromosome probes has allowed a more accurate assessment of the sex chromosal complements in sperm than single FISH method and quinacrine staining for Y-bodies. PMID- 8471254 TI - Developmental ability of enucleated bovine oocytes matured in vitro after fusion with single blastomeres of eight-cell embryos matured and fertilized in vitro. AB - Single blastomeres from eight-cell stage bovine embryos matured and fertilized in vitro were electrically fused with enucleated oocytes matured in vitro. In experiment 1, The percentage of these reconstituted embryos developed to the two- to eight-cell stage 48 hr after electrofusion was increased when both the eight cell embryos and the enucleated oocytes were derived from oocytes cultured with granulosa cells (14% vs. 38%). In experiment 2, the relationship between activation of oocytes and developmental ability of reconstituted embryos was examined. Although both ethanol and electrical stimulation efficiently induced parthenogenetic activation of oocytes matured in vitro for 26-28 hr (ethanol, 89%; electrical stimulation, 73%), the ratio of the second polar body extrusion differed (80% vs. 22%). Ethanol-treated enucleated oocytes, however, were not significantly different from the early cleavage of the reconstituted embryos 48 hr after electrofusion (nontreated, 38%; treated, 43%). In experiment 3, reconstituted embryos at the two- to eight-cell stage 48 hr after the electrofusion were cocultured with granulosa cells for 6-7 days. Of 69 embryos, one developed to a morula and three developed to blastocysts. PMID- 8471255 TI - Separation of bovine X and Y sperm based on surface differences. AB - Aqueous two-phase partition involving thin-layer counter current distribution (TLCCD) has been used to assess surface heterogeneity of ejaculated bovine sperm. When partitioned in charge-insensitive aqueous two-phase systems, which detect non-charge associated surface properties, the sperm fractionates into two distinct populations. Using a Y-chromosome-specific DNA marker, it has been shown that one of these populations is enriched in Y chromosome bearing sperm. However, this population is not pure--it consists of 80% Y sperm, with the other 20% being X sperm. All the sperm in the original population that had begun to undergo the acrosome reaction were separated into this same peak; the sex chromosome composition of these sperm is unknown. Since the aqueous partition of sperm is based on surface properties these results suggest that two populations of Y sperm exist that have different surface characteristics. PMID- 8471256 TI - In vitro maturation of oocytes from a marsupial, the tammar wallaby (Macropus eugenii). AB - This study examined the competence of oocytes from the tammar wallaby, Macropus eugenii to mature in vitro. Oocytes were collected from follicles > 1 mm diameter 24 h after pregnant mare serum gonadotrophin (PMSG) treatment and incubated in Eagle's minimum essential medium supplemented with 10% fetal calf serum, at 35 degrees C in 5% CO2 in air for 24, 36, or 48 h. Oocytes were incubated either granulosa cell-intact or granulosa cell-free or in the presence of 10 IU ml-1 PMSG or 10 micrograms ml-1 porcine luteinizing hormone (LH) + 10 micrograms ml-1 porcine follicle stimulating hormone (FSH). The ability of oocytes recovered from small (< 1.5-mm-diameter) and large (> or = 1.5 mm-diameter) follicles to mature in vitro was also examined. The nuclear status of oocytes was assessed using the DNA-specific dye Hoechst 33342. Initially, all oocytes examined contained a germinal vesicle. After 24 h of culture, 60% of oocytes had progressed to metaphase I or anaphase I. After 36 h, approximately 20% of oocytes possessed metaphase II chromosomes, and 20% of oocytes were at metaphase I or anaphase I. At the completion of the 48 h culture period, 40% of oocytes had completed maturation to the metaphase II stage. In vitro oocyte maturation after 48 h was not affected by the presence of granulosa cells, PMSG, or LH and FSH. More oocytes from large follicles (55%) completed maturation by 48 h than from small follicles (20%). Approximately 50% of oocytes remained at the GV stage at all times under all conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471257 TI - Transgenic strategies in reproductive endocrinology. AB - The present discussion surveys some of the recently published studies utilizing transgenic strategies to address questions in reproductive endocrinology. Beginning with a brief introduction of the transgenic method itself, the following areas are covered: 1. Sexual development and Mullerian-inhibiting substance; 2. Hypogonadal mice and hypothalamic GnRH; 3. The GnRH neuron: generation of immortalized rare cell types; 4. Glycoprotein hormones: immortalized cells, development and evolution; 5. Growth hormone and reproduction; and, 6. Gestation and the insulin-like growth factors. In each section, the discussion attempts to be integrative with respect to the significance of the results to physiological, cellular and molecular biology. We believe this approach is appropriate, as transgenic science itself is necessarily an integration of all of these levels of investigation and participation from those working at all levels is needed. PMID- 8471258 TI - Gene introduction into mouse blastocysts via "pricking". AB - It is a well-known phenomenon that cultured mammalian cells that have been pricked in the presence of foreign DNA can be transformed. This micromanipulation 'pricking' technique was applied to mouse blastocysts to determine whether uptake of exogenous DNA would occur in the embryos. The middle region of the inner cell mass (ICM) was pricked three times in each blastocyst in a medium containing a linearized plasmid DNA. When the 60 treated blastocysts were transferred to the uterine horns of pseudopregnant females, 30 developing fetuses (50%) at the mid gestation stage were obtained. Twenty-two of the 30 fetuses (73%) had less than 1 copy of the foreign DNA per diploid cell, as revealed by polymerase chain reaction (PCR)-Southern analysis, a sensitive technique combined with Southern blot processing of the PCR products. The 8 other fetuses were negative for the foreign DNA. When blastocysts were pricked in the presence of vector DNA coupling E. coli beta-galactosidase (beta-gal) gene to a mouse metallothionein-I (MT-I) promoter and assessed for beta-gal activity histochemically after 1 and 5 days of culture in the presence of 1 microM CdCl2, at least 65% of the embryos exhibited beta-gal activity mainly in the ICM region. These results indicate that mouse blastocysts can be transfected with a relatively high efficiency after pricking, and that the introduced gene expression occurs. This approach provides a means of mapping the regulatory elements of genes that are active in the mouse blastocyst ICM, and may be useful in investigating the fate of the ICM cells in an intact blastocyst by labeling them via pricking technique. PMID- 8471259 TI - Progressive expression of trophoblast-specific genes during formation of mouse trophoblast giant cells in vitro. AB - The expression of a battery of trophoblast-specific mRNAs was studied during trophectoderm development in vivo and in vitro to assess the use of these mRNAs as markers of trophoblast differentiation and to examine lineage relationships between various trophectoderm derivatives. In situ hybridization of sectioned day 6.5-18.5 mouse embryos localized mRNAs for mouse placental lactogens I and II and mouse proliferin (PLF) to trophoblast giant cells and proliferin-related protein mRNA to the spongiotrophoblast and giant cell layers. A fifth marker, cDNA 4311, was found only in spongiotrophoblast. Day 3.5 blastocyst outgrowths and day 7.5 diploid extraembryonic ectoderm (EX) and ectoplacental cone (EPC) were then cultured to produce polyploid giant cells in vitro. Cultures were processed for in situ hybridization after 2, 4, or 6 days. EX and EPC both formed secondary giant cells, which expressed all markers in the same sequence as was observed in vivo, and primary giant cells in blastocyst outgrowths expressed the early giant cell markers PLF and PL-I on days 4 and 6 of culture. EPC progressed through the sequence 2 days ahead of EX, indicating commitment of EPC to giant cell formation. These results suggest that EX, EPC, and primary and secondary giant cells all share in a common pathway of differentiation and that the highly ordered sequence of gene expression characteristic of this pathway occurs similarly in vivo and in vitro. PMID- 8471260 TI - The protective action of betaine on the deleterious effects of NaCl on preimplantation mouse embryos in vitro. AB - The development of outbred mouse (CF1) zygotes in vitro has been studied using medium SOM in which the concentrations of NaCl (85, 105, 125 mM), glutamine (0, 1, 2 mM), and betaine (0, 1, 2 mM) were varied. The effects of the compounds were studied using a 3(3) factorial experimental arrangement. The inhibitory effect of relatively high concentrations of NaCl and the protective effect of glutamine were confirmed. Betaine, an organic osmolyte, can also protect against the deleterious effects of relatively high concentrations of NaCl. The intracellular contents of potassium and sodium have also been measured in single zygotes using X-ray electron probe spectrometry. When medium SOM contains 85 mM or 125 mM NaCl, the intracellular content of Na rises and the content of K decreases. These changes are partially reduced in the presence of 125 mM NaCl if betaine is also in the medium. Betaine has no effect on the intracellular content of K and Na if the concentration of NaCl is 85 mM. These results suggest that organic osmolytes may be required in embryo culture media to prevent excessive changes in the intracellular ionic concentration. PMID- 8471261 TI - Process of nuclear envelope reduction in spermiogenesis of a mosquito, Culex tigripes. AB - When the Culex tigripes spermatid begins to elongate, the nucleus exhibits on its surface invaginations of the nuclear envelope. These invaginations have a uniform diameter of 0.3 microns. They separate from the envelope of the nucleus and form spherical intranuclear vesicles. In the old spermatids these vesicles are imprisoned in the condensed chromatin. The spermatozoon also possesses these vesicles which are then ovoid in shape. This process of vesiculation permits the diminution of the surface of the nucleus when it decreases in volume during spermiogenesis. PMID- 8471262 TI - Noninvasive chemical enucleation of mouse oocytes. AB - A noninvasive method of enucleating mouse oocytes has been developed and evaluated. Strong chromosome to chromosome binding was induced by culturing early metaphase I oocytes in etoposide supplemented medium. Subsequent expulsion of the entire chromosome complex during polar body extrusion was facilitated by exposing the etoposide treated oocytes to a combination of cycloheximide and etoposide during anaphase and telophase. This simple two-step chemical enucleation procedure yields fully enucleated mouse oocytes in 96% of cases. Chemically enucleated oocytes do not contain maturation promoting factor (MPF) at the end of etoposide-cycloheximide enucleation. MPF levels are, however, restored during subsequent incubation in drug-free medium and, after 15 h of post-enucleation culture, the cytoplasts regain their full capacity for parthenogenetic activation and nuclear remodelling. We believe that this novel enucleation technique will greatly facilitate the research in nuclear transplantation. PMID- 8471263 TI - Control of in vitro maturation of bovine cumulus-oocyte complex by preovulatory granulosa cells. AB - The present study was designed to investigate 1) the influence of the secretions of follicular cells on the in vitro maturation of bovine cumulus-oocyte complexes (COCs) and 2) the origin of the factors controlling the metabolic function of cumulus cells during the preovulatory period. Preovulatory granulosa cells were collected from synchronized heifers either before or 7-9 hr after the luteinizing hormone (LH) surge, and their secretions were recovered after a 3 hr incubation. Follicular fluids (FFs) originating from the same follicles and sera from the same animals were also collected. The effects of FFs, sera, and secretions of granulosa cells on COC metabolism were compared during 24 hr of culture. FF stimulated cumulus expansion, progesterone secretion, and overall protein synthesis by COCs but decreased the amount of a major protein of 28 kDa. The time at which FF was collected influenced both cumulus expansion and protein synthesis by COCs. The effects of FF on COC metabolism were detected at the lowest protein concentration studied (0.073 mg/ml) and could be mimicked with serum, but only at a protein concentration 100-fold higher. The inhibitory effect of FF and serum on the amount of the 28 kDa protein was reproduced with the secretions of granulosa cells, acting at protein concentrations five- and 500-fold lower, respectively. However, the secretions of granulosa cells enhanced slightly cumulus expansion and had no effect on progesterone secretion and overall protein synthesis by COCs. These results suggest that COC metabolism is influenced both by endocrine and by local factors secreted by granulosa cells in response to gonadotropins. The paracrine control of COC metabolism by preovulatory granulosa cells could be exerted not only via intercellular contacts but also via substances secreted in FF. PMID- 8471264 TI - Production of cumulus expansion enabling factor by mouse oocytes grown in vitro: preliminary characterization of the factor. AB - The objective of this study was to determine whether fully grown oocytes, obtained after isolation from preantral follicles and growth in vitro, secrete paracrine factors affecting granulosa cell development and function. If so, the relative ease in producing oocytes in this way could facilitate the identification and characterization of the factors. As a test of this idea, the ability of in vitro grown oocytes to produce a paracrine factor that is known to enable the isolated cumulus oophorus to undergo expansion in response to follicle stimulating hormone (FSH) was determined. Initial experiments compared culture systems, which differed in the orientation of the oocyte-granulosa cell complexes from preantral follicles to an extracellular matrix, for their ability to support oocyte growth and the acquisition of competence to resume meiosis. The systems for culture on the surface of the matrix produced larger oocytes and the highest percentage of oocytes having competence to resume meiosis. Oocytes grown using this system secreted active cumulus expansion enabling factor, albeit at levels about half that of oocytes grown in vivo. A preliminary characterization of the cumulus expansion enabling factor secreted by the oocytes grown in vitro showed that activity was lost upon treatment with either heat (65 degrees C for 15 min) or proteinase K. Activity did not pass through a membrane having a nominal molecular weight limit (NMWL) of 100 kd but did pass through a membrane having a NMWL of 300 kd. It is concluded that cumulus expansion enabling factor is secreted by oocytes grown in vitro. This factor is probably a protein or depends upon a protein for its activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471265 TI - Effects of polyamine biosynthesis inhibitors on the progesterone-initiated increase in intracellular free Ca2+ and acrosome reactions in human sperm. AB - This laboratory has previously reported that progesterone can initiate a rapid transient increase in the concentration of intracellular free Ca2+ ([Ca2+]i) and an increase in a Ca(2+)-requiring exocytotic event, the acrosome reaction (AR) in human sperm. Rapid increases in Ca2+ fluxes of some mammalian cells caused by another steroid, testosterone, require polyamine biosynthesis. Herein, we tested two polyamine biosynthesis suicide inhibitors for their effects on the progesterone-initiated increase in [Ca2+]i and AR in capacitated human sperm in vitro: DL-alpha-(difluoromethyl)ornithine hydrochloride (DFMO), an inhibitor of putrescine synthesis by ornithine decarboxylase and (5'[[(Z)-4-amino-2 butenyl]methylamino]-5'-deoxyadenosine (MDL 73811), an inhibitor of S adenosylmethionine decarboxylase (required for spermidine and spermine synthesis). Sperm were capacitated in vitro and preincubated 10 min with 4.9 mM DFMO or 9.8 microM MDL 73811 with or without various polyamines (245 microM). Progesterone (3.09 microM final concentration) or progesterone solvent (ethanol, 0.1% final concentration) was then added, sperm fixed 1 min after additions and AR assayed by indirect immunofluorescence or with fluorescein-labeled Con A lectin. DFMO strongly inhibited the AR, but putrescine (product of ornithine decarboxylase and precursor of spermidine and spermine) reversed that inhibition. Preincubation for 25 min with DMFO + spermidine also reversed DFMO inhibition. MDL 73811 inhibited the progesterone-initiated AR, and a 10 min preincubation with spermidine, but not putrescine or spermine, reversed that inhibition. Preincubations with putrescine alone or with spermidine alone followed by addition of the progesterone solvent did not initiate the AR, and such preincubations followed by progesterone addition did not increase the AR more than progesterone alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471266 TI - Changing physicians' attitudes, knowledge, and self-efficacy regarding cholesterol screening and management. AB - The National Cholesterol Education Program (NCEP) has identified a need to convey practical approaches for the management of high blood cholesterol (BC) to physicians. Our study was a joint effort between the Pawtucket Heart Health Program and the Brown University Department of Family Medicine to improve family medicine residents' attitudes, knowledge, self-efficacy, and practices regarding cholesterol screening and management. Thirty-six resident physicians received a BC screening and management training program. This program included training in BC screening using the fingerstick method and a desktop analyzer, diet assessment and counseling, and a management protocol for evaluation and treatment of high BC based on NCEP guidelines. The training program also included evaluation of residents' BC screening activity, incentives, chart audits, and biweekly articles in the departmental newsletter. We administered a survey to residents before and one year after the training program began to assess self-reported knowledge, attitudes, self-efficacy, and practices for BC management. Survey results indicated that the residents significantly improved their reported knowledge and attitudes about BC management. In addition, they significantly increased their reported self-efficacy and practices in dietary counseling and patient education. Residents also indicated that the training program was worthwhile, necessary, and practical and that many would use the materials and protocols in their future practices. PMID- 8471267 TI - Cancer prevention practices and continuing education needs of primary care physicians. AB - We surveyed 1,500 primary care physicians in Massachusetts regarding their current attitudes and practices, as well as their interests and preferences in regard to a continuing education course, in cancer prevention and screening. Thirty-three percent (n = 488) of physicians returned questionnaires, with equal distribution among internists, family practitioners, and gynecologists. Our findings are based on physicians' self-report: 80%-92% of physicians routinely perform or order breast, cervical, skin, prostate, and colon examinations (with the exception of proctoscopy) for asymptomatic patients 50 years of age and older. Perceived barriers reported were as follows: for mammography, patient age older than 75; for sigmoidoscopy, cost; for counseling, lack of educational materials. Ninety-one percent of physicians rated a comprehensive course on cancer detection and prevention emphasizing practical matters and offering opportunity to upgrade clinical skills in physical exam and in counseling as somewhat to very useful. Specific topic preferences varied by specialty, but first preference for all three primary care groups was a course in improving their office management of cancer prevention and screening activities. Most appealing to practitioners was a one-day course leading to accreditation in screening and prevention and to reduction in malpractice premiums. PMID- 8471268 TI - Development of a knowledge test in the science of prevention of lung diseases. AB - We developed a 50-item multiple choice test to assess knowledge of preventive pulmonary medicine. We derived the content of test items from a comprehensive preventive pulmonary curriculum, which we developed. The test was administered to 167 medical students, residents, and practicing physicians to establish its psychometric properties and to determine if the test scores discriminated between different levels of training. Using this sample, the reliability of the test was 0.86, and the test significantly differentiated between levels of training in pulmonary medicine. We are using this multiple choice test to assess changes in knowledge of second-year medical students and of fourth-year medical students completing a pulmonary medicine elective rotation. PMID- 8471269 TI - Educating medical students and residents as health protectors and patient advocates. PMID- 8471270 TI - Prevention in the medical curriculum: reform and opportunity. PMID- 8471271 TI - Improving the practice of prevention. PMID- 8471272 TI - Occupational medicine: defining core values and skills. PMID- 8471273 TI - Disease prevention policy under Medicare: a historical and political analysis. AB - I review the history and politics of Medicare disease prevention policy and identify factors associated with the success or failure of legislative initiatives to add preventive services benefits to Medicare. Between 1965 and 1990, 453 bills for Medicare preventive services were introduced in the U.S. Congress, but not until 1980, after 350 bills had failed, was the first preventive service added to the Medicare program. Medicare currently pays for only four of the 44 preventive services recommended for the elderly by the U.S. Preventive Services Task Force (pneumococcal and hepatitis B vaccinations, Pap smears, and mammography). In addition, Congress has funded demonstration programs for the influenza vaccine and comprehensive preventive services. The preventive services added to Medicare reflect the bias of the biomedical model toward screening and immunizations. Counseling services have received the least legislative attention. Factors associated with successful enactment include single-benefit bills, incorporation into budget-deficit reduction legislation, documented evidence of cost-effectiveness, public hearings, sponsorship by chairs of key congressional committees, and persistent congressional leadership. Factors associated with failure include lack of support from Medicare beneficiaries, lack of professional support, impact on total Medicare expenditures, disagreement over or failure to address payment and financing mechanisms, and competing congressional priorities. PMID- 8471274 TI - Assessment of community-level influences on individuals' attitudes about cigarette smoking, alcohol use, and consumption of dietary fat. AB - A basic premise of community-based health promotion is that enduring changes in health behaviors are facilitated by changing community norms or the standards of acceptable behavior in the community. We examine whether community-level influences on individuals' normative attitudes can be related to cigarette smoking, alcohol consumption, and dietary fat intake. We conducted a random-digit dialing survey of 8,849 adults in 15 communities in the western United States as part of the evaluation of the Henry J. Kaiser Family Foundation Community Health Promotion Grant Program. We found independent associations among attitudes for tobacco, alcohol, and diet and both individual-level and community-level characteristics. A significant community effect on attitudes remained even when we controlled for individual demographics and health behaviors, as well as for the overall prevalence of the target health behavior in the community. The specific community characteristics that account for this effect were not clear in our analyses, suggesting that influential characteristics vary from community to community. PMID- 8471275 TI - Use of cocaine during the immediate prepartum period by childbearing women in Ohio. AB - Despite widespread concern about exposure of infants in utero to cocaine, population-based data regarding the prevalence of such exposures are limited. An official task force in Ohio called for studies to generate such data for that state. During three weeks in late 1990, urine was obtained within 48 hours of birth from 1,819 infants born in 25 Ohio hospitals randomly selected from a pool of hospitals accounting for over 80% of Ohio births. Maternal age, race/ethnicity, and residence information were collected so that results could not be linked to individual mothers or infants. Urines were screened for benzoylecgonine (BZE), a cocaine metabolite, using a commercially available immunoassay. The crude prevalence of BZE positivity was 2.0%. When adjusted for unequal cluster sizes and race/ethnicity, the prevalence was 1.4%. The adjusted prevalence for infants born to black mothers was 7.2%, for infants born to white mothers, 0.3%. Ninety-seven percent of the mothers whose infants tested positive were residents of a city of 20,000 or more people. The use of hospital maternity units as a basis for anonymous sampling, as demonstrated in this study, may be a useful model for other jurisdictions seeking population-based data concerning perinatal drug exposures. Such methods may be especially useful for trend studies and program evaluation. In this study, we found widely distributed prepartal cocaine usage in Ohio. Black newborns were significantly more likely than white newborns to show evidence of recent cocaine exposure. PMID- 8471277 TI - Development and validation of an immunization tracking system in a large health maintenance organization. AB - Practitioners seeing individual patients and those charged with improving immunization practices in that population need accurate information on the epidemiology of immunizations within the population. To meet this need, we have developed a computer-based record of data required by the National Childhood Vaccine Injury Act of 1986 for all immunizations given to 350,000 enrollees in a large health maintenance organization. In the first eight months of operation, 102,271 immunizations representing 11 separate antigens given to 65,676 enrollees were entered into the database. Comparison of immunizations given and recorded in the medical record with the database shows that the system has high sensitivity, specificity, and positive predictive value, but a relatively low negative predictive value. The database is being used for analysis of current immunization practices for Haemophilus influenzae b vaccine and for research on adverse outcomes of childhood immunizations. PMID- 8471276 TI - Sexual risk and perception of risk for HIV infection among multiethnic family planning clients. AB - Little is known about the relationship among having risks for human immunodeficiency virus (HIV) infection, perceiving oneself at risk, and initiating risk reduction for young sexually active women. We surveyed a multiethnic sample of 267 young-adult female family planning clients attending Planned Parenthood clinics to determine these relationships. Perceiving oneself at risk was significantly associated with having sex outside of a primary relationship in the past year, with having five or more sexual partners in the last five years, and with having a primary partner who has other partners. We found no significant relationship between perceiving oneself at risk and adopting risk-reduction strategies, such as inquiring about a partner's risks or using condoms. These data suggest that the women in this population may be overly optimistic about their invulnerability to HIV. While those women who perceived themselves to be at risk for becoming sexually infected with HIV were more likely to report high-risk behaviors, perception of risk did not motivate these women to adopt low-risk behavior. These data suggest that simple HIV education and acknowledgement may have little effect on reducing exposure to HIV among the women in this population. Alternative strategies for reducing risk must be explored. PMID- 8471278 TI - [Prognostic value of the degree of differentiation and the peri-tumor lymphoid infiltration in epidermoid carcinoma of the larynx]. AB - By multiple linear regression the authors show a closed relationship between survival and conventional anatomopathologic data as grade of differentiation and of lymphoid infiltration of the primary tumor. This retrospective pathological study showed that various degrees of squamous cell differentiation may be recognized for malignant laryngeal lesions and that such distinction may be of prognostic significance. PMID- 8471279 TI - [Interaction of arterial blood pressure and industrial noise on human hearing]. AB - A cross-sectional study of occupational noise exposure and high blood pressure was conducted in a group of 1584 workers. Clinical examination, audiograms, and body mass index were compared in exposed and not to noise finding a strong relationship between severe noise induced hearing loss and high blood pressure in all the staff, as it has been marked by different authors. But when we stratify the population in groups of age, we can't find any influence between noise exposure and hypertension, or between the appearing of high blood pressure and noise induced hearing loss. PMID- 8471280 TI - [Results of tracheal reconstructive surgery using homografts preserved in formaldehyde]. AB - The present study was designed to investigate the results of homograft of cervical trachea preserved in formaldehyde. Surgical approach consists in end-to end anastomosis. In all our cases the graft was rejected, and the animals could only live 13 days as a maximum. We find tracheal mucosa is responsible for graft antigens. The results both clinical and histopathological are compared with a control group and with those obtained by other authors using different conservation methods. PMID- 8471281 TI - [Clinicopathologic prognostic factors in laryngeal and pharyngolaryngeal tumors. I. Carcinoma of the pyriform sinus]. AB - Prognostic factors of pyriform sinus carcinomas were studied in 122 patients. The 5-year determinate survival was 25.8%. Factors that implied a bad prognosis were an advanced local and nodal stage, and the degree of differentiation. At variance, alcohol and tobacco abuse, age, previous tracheostomy, involvement of surgical margins and local complications had not any prognostic significance. PMID- 8471282 TI - [Appropriateness emergency hospital admissions at an ORL service of a third level hospital]. AB - We present a retrospective epidemiological study about an analysis of the emergencies hospital admissions in an ENT service of a tertiary hospital with high assistencial pressure, during one year. We study the parameters: date, sex, age, complementary examinations, diagnosis and appropriateness of the admission following the AEP (Appropriateness Evaluation Protocol) criteria. A remarkable finding is the high incidence (31.74%) of emergency admissions in the total admission in the ENT service. There was a low frequency of inadequate admission of patients. The appropriateness of admissions was highest for foreign bodies and respiratory distress; the lowest was for cancer patients. The most frequent appropriateness criteria was the need of drugs and/or intravenous fluids. PMID- 8471283 TI - [Diagnostic value of auditory brainstem evoked potentials (ABP) in high risk premature and newborn infants]. AB - In this work we have studied 37 children, both preterm and term, belonging ti high risk group of contracting hearing loss, in order to confirm the predictability of ABR in the diagnostic of the congenital hearing losses during the prenatal period and so make possible their immediate and proper rehabilitation. With this purpose we have studied parameters such as threshold, latency of waves and intervals. We have discovered that in preterm children, owing to reasons such as answers of little amplitude, movements of the children and difficulty to determine the gestational age, the parameters of normality are only the existence or not of waves, discarding the value of the threshold and the latency of waves. We have had to wait for 40 weeks to obtain ABR similar to the ones in adults, in which the threshold, latency of waves and intervals are certain to predict hearing. In spite of it all we have to agree that ABR are the best hearing test at those ages. We must not forget that normal ABR could include lesions in the upper part of hearing pathway. PMID- 8471284 TI - [Hypertrophy of lingual ectopic thyroid gland in pregnancy. A clinical case]. AB - A 28-year-old female, diagnosed two years ago of euthyroid lingual thyroid, has been asymptomatic under observation without treatment until her first pregnancy. During her first pregnancy the lingual thyroid tissue increases of size and produces dysphagia, pain and oral hemorrhages. We realize a thyroid hormone treatment (thyroxine) with regular results. Two months after child-birth the female was completely asymptomatic and doesn't need actually thyroxine suppression. Various aspects are reviewed, such as the predisposing factors (puberty, pregnancy, trauma ...), clinical manifestations, diagnosis and medical and surgical treatments in this rara congenital anomaly. PMID- 8471285 TI - [Necrotizing osteitis of tympanal bone. Report of 2 cases]. AB - A large variety of process can cause necrosis of the bony external ear canal, found by means otoscopic examination. Two cases with a final diagnosis or external ear canal cholesteatoma are reported. A revision of the main characteristics of this uncommon entity is performed, with a special emphasis to avoid that the scarcity of clinic symptoms favour its growing in depth. PMID- 8471286 TI - [Eikenella corrodens as a pathogen of lateral cervical abscess]. AB - We show a case of right neck abscess, in which the Eikenella corrodens, acted as pathogen together which other microorganism. We call attention to this germ that has a slow growing in culture and generally intervene in infections in which it is assumed the presence of anaerobic germs (intrathoracic abscess, neck abscess, etc.) and the are habitually treated with clindamycin, antibiotic which Eikenella corrodens is systematically resistant (to this antibiotic). PMID- 8471287 TI - [Hypopharyngeal fibrolipoma: description of a case and review of the literature]. AB - A rare case of hypopharyngeal fibrolipoma is reported. The main symptom which brought the patient to an ENT examination was a severe inspiratory dyspnea. Symptomatology, diagnosis, treatment and follow-up of this benign tumour are described and the literature review is discussed. PMID- 8471288 TI - [Otitis externa caused by Vibrio alginolyticus: description of 4 cases]. AB - Vibrio alginolyticus is a microorganism of marine environment which occasionally may cause infections on man. We described four patients with external otitis who had prolonged contact with sea water presented itch and seropurulent fluid. V. alginolyticus was isolated by pure culture from ear fluid of three of them and associated to V. fluvialis in another. The administration of ciprofloxacin in three cases, and ceftazidime in the other succeeded in the remission of the symptoms. PMID- 8471289 TI - [Multiple symmetric lipomatosis. Madelung syndrome. Report of a case]. AB - We present a case of multiple symmetric lipomatosis. We comment aspects diagnostics and therapeutic. PMID- 8471290 TI - [Evaluation of the diagnostic efficiency of tridimensional reconstruction with nuclear magnetic resonance. Report of a case of nasal sinus carcinoma]. AB - In the past decades the development of magnetic resonance imaging has significantly increased the importance of diagnostic imaging of head and neck lesions. The standard imaging method is base on two-dimensional slices. Recently 3D reconstruction has been established as new imaging method in various medical fields. In the present study we analyse the diagnostic value of the reconstruction method in a case of carcinoma of the maxillary sinus. The results indicate that this technique might be of significant clinical importance for preoperative planning in the case of certain tumors located close to the skull base. PMID- 8471291 TI - [Benign esophagobronchial fistula in an adult]. AB - The case of a senile dementia patient 86 year old, and a supposed clinical history of swallowing a foreign body is presented. After a clinical study (esophagogram, flexible and rigid esophagoscopy and bronchoscopy) and finally the autopsy of the patient, we found and idiopathic esophago-bronchial fistula. PMID- 8471293 TI - Public health education for all? PMID- 8471292 TI - [Neurofibromatosis with laryngeal involvement]. AB - The clinical features of a new case of Von Recklinghausen's neurofibromatosis affecting the larynx, are described. The patient was a three year old boy presenting with hoarseness. The diagnostic and therapeutic features, and the clinical course are described. This is another patient with neurofibromatosis, including laryngeal involvement, to be added to the 26 such cases already described in the world literature. It is the eleventh laryngeal plexiform neurofibroma described. The relevant literature is reviewed. PMID- 8471294 TI - Selective medicals at school entry. PMID- 8471295 TI - International comparisons of health expenditure. PMID- 8471296 TI - Cost of neonatal care across a regional health authority. PMID- 8471297 TI - Junior doctors' work at night: what is done and how much is appropriate? AB - Regional task forces have given some public health physicians a central role in attempts to reduce junior doctors' hours. This topic is the subject of many diverse opinions and little research. A key issue that has received little attention is the appropriateness of the work undertaken by junior doctors at night. This paper determines whether this work can either be postponed to the following morning or done by someone else. It was undertaken in two phases: a descriptive study using diaries, interviews and collection of data from registers; and identification of consensus on appropriateness of activities by a nominal group technique. The first phase took place in hospitals in the South East of England. The nominal groups consisted of six panels comprising medical, nursing and laboratory scientific staff. The panels identified activities done at night that can either be postponed to the following day or done by someone else and activities where there is disagreement, requiring further research. A third of general surgical and orthopaedic operations could safely be postponed until the following day. Up to a third of the tasks of house officers could be performed by nursing or clerical staff. Many laboratory investigations at night could be postponed until the following day. In conclusion, the work of junior doctors at night could be reduced by producing guidelines on the need to operate at night, by transferring tasks to other professionals, and by reducing the number of sites at which services are provided. PMID- 8471298 TI - Disease staging--a case-mix system for purchasers? AB - The National Health Service (NHS) internal market has directed renewed attention at hospital activity data. Purchasers require information on the cost of care provided for them, the quality of service and the extent to which their population's needs are being met. There is a need for a means of condensing the large number of diagnostic codes into groups containing patients with similar outcome or resource use, i.e. case-mix systems. These systems have been developed in the United States to overcome this problem. Unfortunately, they may not be valid or acceptable in other countries. We describe the evaluation of one such system, Disease Staging, in the United Kingdom. We conclude that it can be used with UK data to produce groups that are homogeneous both in terms of length of stay and mortality. Its logic is acceptable to UK clinicians. We discuss the major issues involved in using routine hospital data and suggest ways in which Disease Staging might be used by purchasers in the UK internal market. PMID- 8471299 TI - Breast cancer screening services in three areas: uptake and satisfaction. AB - The objective of our study was to test whether attendance for breast cancer screening and satisfaction with the service could be predicted from a knowledge of the woman's social and psychological characteristics. In a prospective design, demographic characteristics, self-reported health status and behaviour, expectations and attitudes were examined through postal questionnaires sent out shortly before the invitation to screening, and the measures were used to predict subsequent attendance and satisfaction. The sample was taken from three areas in the South-East Thames Regional Health Authority providing a Forrest service--one rural, one provincial and one inner city--and consisted of 3160 women aged 50-64 invited routinely for screening. The main predictors of attendance were the woman's attitude to being screened and her belief that 'salient others' wanted her to attend. The main predictors of satisfaction with the service were the behaviour of the staff and the facilities at the centre. Three implications of the findings are discussed: (a) health education should include partners, relatives and friends of the target women, as their views had as much effect on attendance as did the women's attitudes; (b) staff training and development should focus on communication with the patient; (c) further research should examine the precursors of reported discomfort and pain. PMID- 8471300 TI - Cervical cytology screening: a comparison of uptake among 'Asian' and 'non-Asian' women in Oldham. AB - This study investigates the response of 'Asian' and 'non-Asian' women to a computer-generated invitation to attend for a cervical smear during a one-year period. One hundred and fifty-eight 'Asian' women were compared with 158 non 'Asian' women from four general practices in Oldham; the women were aged between 50 and 64 years and were from a restricted geographical area to control for socioeconomic factors. It was found that there was no difference in the response to the test invitation between the two groups (uptake in 'Asians' 61.5 per cent, 'non-Asians' 60.6 per cent). 'Non-Asian' women were more likely to have had a previous smear than 'Asian' women. The Family Health Services Authority register contained a higher number of inaccurate addresses for 'Asian' women. It is suggested that ethnicity did not seem to play an important part in the uptake of cervical smear testing in this population. PMID- 8471301 TI - Health and length of residence among south Asians in Glasgow: a study controlling for age. AB - To relate health to length of residence in the United Kingdom in an age controlled sample of British South Asians, a cross-sectional survey was undertaken with interviews and physical measures in a two-stage stratified random cluster sample in the City of Glasgow. The sample consisted of 159 South Asians aged 30-40, with a mean age of 35 years (73.6 per cent of those invited). The main measures considered were body structure, lung function, pulse and blood pressure, history of physical and mental health, results of standardized questionnaires on mental health, angina and respiratory health, recent and past symptoms, history of accidents and sickness behaviour. It was found that over a quarter of the health measures showed differences by length of residence, and long-established residents had almost consistently worse results. More were overweight, reported heart trouble and respiratory conditions, had had accidents, experienced symptoms, especially respiratory and psychosomatic, needed glasses and took time ill in bed. Comparisons with North Indian data make it unlikely that these results are explained by positive selection of recent migrants. Also, the results do not endorse the assumption that the UK environment has promoted higher levels of health in migrants longer exposed to it, nor that the stress of the move promotes higher levels of illness in recent migrants. Further investigation is required of ways in which the UK environment, or the particular situation of South Asians within it, may be damaging to health. PMID- 8471302 TI - Alcohol intake and the U-shaped curve: do non-drinkers have a higher prevalence of cardiovascular-related disease? AB - The data from the Oxford Vegetarian Study consists of the observation of around 11,000 individuals followed since the early 1980s. There are around 6000 subjects who do not eat meat and 5000 roughly matched individuals who do. An assiduous questionnaire survey was conducted at recruitment which inquired about health status, diet, drinking and other habits. We have tested the hypothesis that the U shaped curve relating quantity of alcohol consumed and health is an artefact of selection of some individuals with high consumption and high risk migrating to the no-consumption group but retaining a high risk. The Oxford Vegetarian Study consists of a high proportion of lifelong teetotallers and ex-drinkers, and hence is particularly suitable for testing this hypothesis. We have examined the standardized rates of cardiovascular risk factors among the different dietary and drinking groups separately for men and women, as the bulk of the observed relationship of alcohol with health is mediated through cardiovascular mechanisms. We were unable to find a difference in the prevalence of risk factors between ex-drinkers and teetotallers, but we did find differences associated with dietary practices, particularly among females. These data cast some doubt on the hypothesis that selection may explain the apparent protective effect of moderate drinking when compared with groups currently not drinking (for whatever reason) and heavy drinking. PMID- 8471303 TI - Alcohol and pregnancy: an international comparison. AB - A study was set up to compare the drinking habits of women of childbearing age in two cities (Milan and Southampton) in two countries, Italy and the United Kingdom, and to look at the effects of alcohol consumption on the weight of the babies born to these women. The sample consisted of 1516 women in Milan and 996 in Southampton, who were interviewed after delivery; data on their drinking history, before and during pregnancy, were gathered, together with social, demographic and health data. The clinical records of the women and their babies were examined. On average, both groups drank less than one unit/day before pregnancy, but there were differences in drinking habits between the two countries, as well as in the modifications induced by pregnancy. The possible effects of alcohol on birthweight were then considered. After controlling for confounding factors, there was no general association between birthweight and alcohol consumption. The impact on health education policy is discussed. PMID- 8471304 TI - How important is health behaviour to the health of mothers of lower socio economic status? AB - Secondary analysis of the data available from the national sample in the Health and Lifestyle Survey allowed two samples of mothers from Social Classes III Manual and IV+V to be selected and the relationships investigated between two measures of health and a range of potential explanatory variables, including voluntary health behaviour. Analysis of variance was used to establish which sets of factors were significantly and independently associated with each of the measures of health within the two samples. Health behaviour was identified as making an independent, albeit small, contribution in three out of the four analyses. PMID- 8471305 TI - General practitioner referral patterns. AB - A survey of general practitioners (GPs) in the Western Health and Social Services Board was carried out in November 1990. The main objectives were to determine the factors which influence GPs' decisions to refer to particular hospitals and to ascertain current out-patient referral patterns. A self-administered questionnaire was sent to 157 GPs. The response rate was 94 per cent. It was found that waiting lists and personal knowledge of consultants' expertise were considered to be of particular importance in making referral decisions for elective/non-urgent procedures. Referrals were usually made to the nearest hospital with a relevant out-patient clinic. The majority (96 per cent) of respondents indicated that they would be willing to change their referral patterns for elective/non-urgent procedures in response to shorter waiting times. It is concluded that GPs may be more willing to change their referral patterns than might have been expected. PMID- 8471306 TI - A prospective study of non-fatal childhood road traffic accidents: what can seat restraint achieve? AB - A prospective study of children attending an Accident and Emergency Department was carried out at the Royal Aberdeen Children's Hospital, to determine the association between injury risk and seat restraint usage, and to estimate the likely impact of seat restraint usage at various target levels on the incidence of non-fatal injuries. The subjects were all 91 cases of non-fatal childhood road traffic accidents attending the casualty department between December 1989 and November 1990. The main outcome measures were relative risks of three grades of injury severity and four types of non-fatal injury, population attributable risk fractions and estimated likely reduction in incidence of non-fatal injury at three set target levels of seat restraint usage. It was found that 42 (46 per cent) children presenting to the A&E Department were unrestrained; 78 (85.7 per cent) children sustained some injury. The relative risk for children travelling unrestrained in a car for all injuries combined is 1.7 (95 per cent confidence interval (CI) 1.17-2.45), the relative risk for head injury is 3.13 (1.78-5.51) and for face injury 3.03 (1.44-6.37). The risk of sustaining any moderate or worse injury was 3.25 (1.05-10.07). It is estimated that 24.4 per cent (minimum 5.5 per cent; maximum 45 per cent) of all non-fatal injuries sustained by a child car passenger can be prevented if all children are restrained in a child safety seat or seat restraint; 49.5 per cent of head injuries (minimum 43.4 per cent; maximum 71.9 per cent) and 48.4 per cent of face injuries (minimum 21.9 per cent; maximum 75.3 per cent) are preventable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471307 TI - Migration patterns of children with leukaemia and non-Hodgkin's lymphoma in three areas of northern England. AB - As part of a more comprehensive study, complete residential histories were collected from 109 cases of childhood leukaemia and non-Hodgkin's lymphoma who were diagnosed while resident in Gateshead, West Cumbria or North Humberside (1973-1987), and who were born in the same areas. Corresponding data were obtained from the same number of controls matched by date of birth, sex and area of residence at diagnosis and birth. Altogether, 1332 years of residential history were available for analysis and of these 131 (9.8 per cent) included a change of home. Moving house was much more frequent for both cases and controls in the first two years of life (69 out of 432 child-years, i.e. 16 per cent). The moves were mostly over short distances, with only 23 per cent being 5 km or more and only 9 per cent into another administrative district. Twenty-eight per cent of the children had moved house at least once by their second birthday and 48 per cent by the age of five years. Few case-control differences were apparent and none achieved statistical significance. There was a suggestion of more mobility for case children in the first few years of life, especially for cases diagnosed shortly after the removal. When the residence of mothers in the year preceding the childrens' birth was examined, there were relatively few removals in this period (26, i.e. 24 per cent, altogether, of which 14 were over 5 km and nine from another administrative district). Of these, 18 case mothers had moved (11 over 5 km) compared with eight control mothers (three over 5 km).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471308 TI - Population-based trends in treatment rates in psychiatry in Oxfordshire, 1975 1986. AB - Routinely collected abstracts of medical records for patients in Oxfordshire were used to identify each individual's first contact with specialist psychiatric in patient, out-patient or community care services over a 12-year period (1975 1986). During this period first-contact rates for people under 65 years of age declined by 3.3 per cent. The decline was observed for contacts with specialist care outside hospital as well as for in-patient care. It is therefore not attributable simply to a shift away from in-patient care. The decline was seen in most major diagnostic groups including schizophrenia, affective psychosis and the neuroses, and it is therefore not attributable to changing diagnostic practices between these groups. Increases in first-contact rates in this age group were found for alcohol-related disorders in women and self-harm in men. First-contact rates for people aged 65 years and over increased by 3 per cent per year. The condition that mainly accounted for the increase over time was dementia, which was by far the commonest recorded psychiatric diagnosis in this age group. Although the increase was seen in all modes of care, it was the domiciliary visiting service that contributed most to the upward trend. The implications of these trends for service planning and their limitations as measures of changes in morbidity are discussed. PMID- 8471309 TI - Glycosylation of the external domain of SIV gp41 is influenced by the cytoplasmic tail. PMID- 8471310 TI - In vivo administration to rhesus monkeys of a CD4-specific monoclonal antibody capable of blocking AIDS virus replication. AB - Monoclonal antibodies (mAbs) specific for CD4 are potent inhibitors of HIV replication in vitro. These agents may be useful prophylactically or in chronic HIV infection if they can be administered without inducing immunosuppression. In the present study, we explored the safety of a CD4-specific murine mAb in rhesus monkeys. The mAb 5A8, which binds to domain 2 of the CD4 molecule, inhibits AIDS virus replication noncompetitively at a postvirus binding step. This antibody, which had a similar affinity for rhesus monkey and human CD4 cells, efficiently inhibited in vitro replication of both HIV-1 and the simian immunodeficiency virus of macaques. A single 3-mg/kg injection of mAb 5A8 into normal rhesus monkeys coated all circulating and lymph node CD4 cells for 4-6 days. CD4 cells were not cleared from circulation nor was the CD4 molecule modulated from the lymphocyte surface. In fact, administration of mAb 5A8 resulted in an approximately one-to twofold increase in absolute number of circulating CD4 cells. Repeated administration in normal rhesus monkeys resulted in CD4 lymphocyte coating with mAbs for > 9 days without CD4 cell clearance or modulation. While coated with mAbs, PBLs of these monkeys retained normal in vitro proliferative responses to mitogens and these animals generated normal humoral responses in vivo to tetanus toxoid. Loss of cell coating with mAbs in normal monkeys corresponded to the appearance of anti-mouse immunoglobulin antibodies. Thus, administration of certain anti-CD4 mAbs capable of blocking HIV replication can achieve coating of the entire CD4 cell pool in rhesus monkeys without inducing significant cell loss or immunosuppression. PMID- 8471311 TI - The reactivities of HIV-1+ human sera with solid-phase V3 loop peptides can be poor predictors of their reactivities with V3 loops on native gp120 molecules. AB - The binding of HIV-1+ human serum antibodies to solid phase-adsorbed V3 loop peptides from the IIIB, SF-2, and MN isolates was compared with the abilities of the same peptides to inhibit binding of the sera to the homologous or heterologous native gp120 molecules. The reactivities of the sera with the solid phase peptides were found to be poor predictors of the potencies of the peptides as competitors in solution for antibody binding to the V3 loop in situ. Furthermore, the extent of cross-reaction of HIV-1+ human serum antibodies with the three V3 peptides in solid-phase assays was potently influenced by the presence or absence of nonionic detergent. Because the use of solid-phase V3 peptide assays is widespread, and there is no consensus on the use or omission of detergent, there is considerable potential for confusion. These factors should be considered when interpreting data derived from V3 peptide serology when this method is used to dissect the human immune response to HIV-1 infection. It is also shown in quantitative studies of HIV-1+ serum antibody binding to homologous and heterologous gp120s that the general anti-gp120 antibody response is significantly "type specific" for the homologous gp120. PMID- 8471312 TI - Complement activation by gp160 glycoprotein of HIV-1. AB - The ability of the gp160 envelope glycoprotein of HIV-1 to activate human complement and to bind C3 fragments was investigated by incubating mammalian derived recombinant gp160 with seronegative serum and by quantitating the binding of C3b/iC3b to the protein using a biotinylated monoclonal antibody directed against a neoepitope expressed by cleaved human C3. Recombinant gp160 activated complement in a dose- and time-dependent fashion. Complement activation occurred through the classical pathway, independently of antibodies, and required C1q. Binding of anti-HIV IgG to rgp160 prior to exposure of the envelope glycoprotein to serum resulted in enhanced complement activation. Complexes of rgp120 with anti-HIV IgG also cleaved C3 in serum, resulting in deposition of C3b on gp120. These results provide a basis for C3-mediated facilitation of viral entry into target cells expressing receptors for fragments of human C3. PMID- 8471313 TI - Induction of human immunodeficiency virus-specific T cell responses in rhesus monkeys by synthetic peptides from gp160. AB - We have previously identified several synthetic peptides from conserved regions of the human immunodeficiency virus (HIV) envelope protein gp160 that have the capacity to induce broadly reactive T cell responses against gp160 in mice of several major histocompatibility complex (MHC) haplotypes. In the present investigation three rhesus monkeys were immunized with a mixture of eight synthetic peptides that are capable of inducing T cell activity in mice. Peripheral blood mononuclear cells (PBMCs) from these monkeys were monitored every 2 weeks for a period of 34 weeks for proliferative responses against individual peptides and recombinant gp160. Peripheral blood mononuclear cells from all three rhesus monkeys showed good proliferative responses with peptides 104 (aa 45-55), 111 (aa 118-130), and 63 (aa 519-543), whereas weak responses were observed with peptides 113 (aa 204-216) and 116 (aa 240-252). Two of the three rhesus monkey-derived PBMC preparations also showed good proliferative responses with peptide 61 (aa 586-598). Significant responses were not observed with peptides 105 (aa 48-61) and R15K (aa 315-329) in any of the monkeys immunized. However, PBMCs from all three monkeys showed significantly high proliferative responses with recombinant gp160, the HIV-1 envelope protein precursor. These results demonstrate that mixtures of synthetic peptides from HIV env gene product can prime gp160-specific T cell responses in rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471314 TI - T cell response to staphylococcal superantigens by asymptomatic HIV-infected individuals exhibits selective changes in T cell receptor V beta-chain usage. AB - Recognition that the murine mammary tumor C-type retrovirus and the replication defective murine leukemia virus have "superantigen" properties raises the specter that human immunodeficiency virus might also generate T cell impairment and destruction as a result of inherent superantigen properties. The observation that individuals with AIDS lack the expression of several T cell receptor V beta-chain genes lends support to this hypothesis. Staphylococcal exotoxins represent another class of superantigen with a similar ability to stimulate large numbers of T cells bearing specific T cell receptor V beta-chain types. To examine the hypothesis that T cells from HIV-infected individuals may be exposed to a superantigen during the infection process, we have compared the ability of T cells from asymptomatic HIV-infected donors and healthy donors to respond to stimulation with several known staphylococcal exotoxin superantigens. Following in vitro stimulation with staphylococcal enterotoxin D and staphylococcal enterotoxin E, asymptomatic HIV-infected individuals responded with a significantly different T cell receptor V beta-chain usage to that observed for healthy individuals. This skewed V beta-chain usage is likely to reflect preferential conditioning of T cells bearing specific V beta-chains as a result of HIV infection, supporting the hypothesis of superantigen involvement early in the course of infection. PMID- 8471315 TI - Human immunodeficiency virus type-1 antibody in 6703 institutionalized mentally retarded clients: an unlinked serosurvey at seven California developmental centers. AB - All clients residing in seven California developmental centers were tested for human immunodeficiency virus type 1 (HIV) antibody in an unlinked serosurvey. Of 6703 clients, 11 (0.16%) were found positive for HIV-1 antibody by confirmatory Western blot and immunofluorescent antibody tests. Universal blood and body fluid precautions should be rigorously enforced to prevent institutional spread of HIV even in this low-risk population. PMID- 8471316 TI - Humoral aspects of anti-HIV immune responses in Zairians with AIDS: lower antigenemia does not correlate with immune complex levels. AB - Serological patterns of anti-HIV immune responses of 150 HIV-infected (65 asymptomatic, 19 ARC, 66 AIDS) and 150 HIV-negative healthy Zairians were studied to determine the clinical significance of p24 antigen, and anti-p24 antibody, particularly in relation to p24 relative binding capacity (RBC) and circulating immune complexes (CICs). Levels of p24 antigen, anti-p24 antibody titers, and p24 RBC were evaluated by means of enzyme-linked immunosorbent assay (ELISA). Circulating immune complexes were measured by C1q-binding assay. Human immunodeficiency virus CICs were detected by polyethylene glycol (PEG) precipitation followed by 6 M guanidinium lysis, ELISA, Western blot, or radioimmunoprecipitation of the lysed precipitates. Immunoglobulin levels for IgG, IgM, IgA, and beta 2-microglobulin (beta 2-M) were quantified in all study participants by laser nephelometry and ELISA. All immunoglobulin levels were significantly elevated among HIV-positive vs. HIV-negative individuals. Immunoglobulin levels correlated well with disease progression among infected patients. Similarly, beta 2-M levels were significantly higher in HIV-positive vs. HIV-negative individuals and correlated well with progression to AIDS. Free p24 antigen in serum was detected in 1.33% of all patients. However, p24 reactivity increased to 6% (9 of 150 cases) after PEG precipitation and CIC dissociation. There was a good correlation between p24 reactivity and disease development. High titers of anti-p24 antibody (> 44,100) occurred in at least 80% of all patients, and did not correlate with disease stage. Similarly, more than 60% of patients had high levels of p24 RBC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471317 TI - Detection of HIV-1 distribution in different blood fractions by two nucleic acid amplification assays. AB - A new amplification procedure, NASBA (nucleic acid sequence-based amplification), was used together with the polymerase chain reaction (PCR) to detect HIV-1 sequences in different blood fractions of both HIV-infected and uninfected samples. We tested whole blood, plasma, peripheral blood mononuclear cells (PBMCs), and platelets. No HIV-1 sequences were found in blood fractions of 37 uninfected persons either by PCR, reverse transcriptase-PCR (RT-PCR), or NASBA. We found that none of the infected plasma samples contained HIV-1 DNA sequences. However, a high percentage of these plasma samples was positive for HIV-1 RNA: 86% by NASBA and 80% by RT-PCR. The concordance on a sample-to-sample basis of NASBA and RT-PCR was 91%. Only 33% of the plasma samples was HIV-1 p24-antigen positive, demonstrating the superior sensitivity of amplification procedures. We found that almost all PBMC fractions were positive for HIV-1 (pro)viral sequences (99% HIV-1 DNA positive, 91% HIV-1 RNA positive). A large proportion of the platelet fractions contained HIV-1 RNA, as demonstrated by positive RT-PCR and NASBA results. We found an inverse relation between CD4+ T cell count and T cell reactivity on the one hand and detection of HIV-1 sequences by PCR, RT-PCR, and NASBA on the other hand in all blood fractions. Quantification of the HIV-1 PCR signal in PBMCs revealed an inverse relation of proviral titers with CD4+ levels. This finding supports earlier observations that clinical disease and low CD4+ cell counts are related to an increased viral burden. PMID- 8471318 TI - Cutaneous disorders and viral gene expression in HIV-1 transgenic mice. AB - Patients infected with HIV-1 experience several hyperproliferative skin disorders, including seborrheic dermatitis, ichthyosis, and psoriasis. Transgenic mice carrying a subgenomic HIV-1 proviral construct lacking the gag and pol genes were found to develop proliferative epidermal lesions, manifested as diffuse epidermal hyperplasia in homozygous transgenic mice and benign papillomas in heterozygous transgenic mice. Nonpapillomatous skin from both homozygotes and heterozygotes expressed viral RNA, and the viral envelope protein gp120 was localized to the suprabasal keratinocyte. Papillomas contained increased amounts of both viral mRNA and envelope glycoprotein. Exposure of transgenic mice to doses of ultraviolet B (UV-B) irradiation that induced cutaneous injury increased viral gene expression and resulted in the development of papillomas within 14-21 days. Cutaneous injury induced by phenol and liquid nitrogen had similar effects. These data support a role for HIV-1 gene products in the pathogenesis of proliferative epidermal disorders associated with HIV-1 infection. Further, they suggest that the process of wound repair increases HIV-1 gene expression in this transgenic mouse model. PMID- 8471320 TI - New concepts in AIDS pathogenesis. AB - The concept that HIV causes AIDS only by directly killing CD4 cells has been questioned by a number of investigators. There has been experimental support for a number of indirect mechanisms such as apoptosis, anergy, superantigen-induced cell proliferation and depletion, defective signaling, molecular mimicry, and autoimmunity. In this article we review the available evidence in support of these theories and suggest that in spite of their apparent differences, signaling by HIV through the T cell receptor could initiate the markedly different responses of activation, anergy, and apoptosis. However, the unifying mechanism as to how this is achieved remains unclear. It is likely that more than one of these mechanisms are involved in CD4 cell depletion during different phases of the disease. Understanding these mechanisms and their role in HIV pathogenesis would be important in new vaccine and therapeutic approaches. PMID- 8471319 TI - Early pathogenesis of disease caused by SIVsmmPBj14 molecular clone 1.9 in macaques. AB - We have studied the early pathogenesis of infection by molecular clone 1.9 of SIVsmmPBj14 in pig-tailed and cynomolgus macaques. Like the uncloned PBj14 parent, SIVsmmPBj14-1.9 consistently induced an acute clinical syndrome characterized by behavioral depression, fever, profuse diarrhea, dehydration, lymphadenopathy, splenomegaly, and mucocutaneous exanthema that began at 7 days postinfection (DPI). The acute clinical disease coincided with a marked cell associated and cell-free viremia, during which SIV p27 was demonstrated in 4 to 68% of circulating mononuclear leukocytes between 4 and 17 DPI. Also characteristic were monocytosis and reductions in CD4+ and CD8+ T lymphocytes, as well as CD20+ B lymphocytes. The most profound depletion occurred in the CD44hi subset of CD4+ T cells. Unlike animals infected previously with uncloned or biologically cloned PBj14, however, all SIVsmmPBj14-1.9-infected macaques survived the acute-phase disease to progress to a chronic, largely asymptomatic phase of infection. Recovery from the acute-phase disease correlated with down modulation of virus replication and the appearance of antibodies to SIV Env and Gag proteins. Similar to the PBj14 parent, PBj14-1.9 targeted to intestine, spleen, bone marrow, lymph node, and cerebellum. Saliva contained substantial quantities of infectious virus and no viral antibodies during the early phase of infection. By contrast, saliva from chronically infected animals usually contained antibodies but no virus. This study extends previous work demonstrating that the acute clinical syndrome produced by SIVsmmPBj14 in pig-tailed macaques represents a unique model of lentiviral pathogenesis. PMID- 8471321 TI - Cancer epidemiology and privacy laws: recent trends in Germany. PMID- 8471322 TI - Increased incidence of sarcoma in patients treated for testicular seminoma. AB - In a nationwide cancer registry analysis of second primary malignancies in 6187 men with testicular cancer in the period 1943-1987, 13 sarcomas were found, yielding a 4-fold increase of the relative risk (RR). The majority of sarcomas occurred in men with seminoma, and the increased incidence was seen irrespectively of time since the diagnosis of testicular cancer. The interval between the testicular cancer and the sarcoma varied from 5-34 years. After investigation of the hospital records and re-examination of the histological specimens, 3 patients were excluded. In spite of this, the RR was still considerably increased (at least 3-fold). Seven of the 10 sarcomas were found to be located within the field of the radiation treatment administered and three at the periphery. The absolute number of these secondary sarcomas is low, but the risk of developing such neoplasms and other malignancies should, even so, be kept in mind in the follow-up of testicular cancer patients. PMID- 8471323 TI - Induction chemotherapy and intensification with autologous bone marrow reinfusion in patients with locally advanced and disseminated breast cancer. AB - In 56 patients with disseminated or locally advanced breast cancer it was attempted to reach a state of no evidence of disease by a remission induction regime containing prednisone, 5-fluorouracil, methotrexate, doxorubicin and vincristine. If successful, patients received an intensification regimen consisting of cyclophosphamide (7 g/m2) and etoposide (1.5 g/m2) with autologous bone marrow reinfusion. The complete remission rate of the induction regimen was 52% and the partial remission rate 42%. 32 patients received the intensification regimen. Two toxic deaths occurred. The median time to disease progression in the group with disseminated disease was 15 months. After a median observation of 4 years, 11 out of 19 patients with locally advanced breast cancer were free of disease. It is concluded that this approach may lead to prolonged disease-free survival in patients with locally advanced breast cancer, but does not influence the survival in disseminated disease. PMID- 8471324 TI - Incidence of second primary cancer following testicular cancer. AB - The incidence of second primary cancers was investigated in 6187 Danish men diagnosed with testicular cancer in the period 1943-1987. During the course of 59,000 person years, 459 subsequent primary cancers occurred. The relative risks were significantly increased for leukaemia, gastric cancer, pancreatic cancer, bladder cancer, non-melanoma skin cancer and kidney cancer. Increased incidence was furthermore suggested for cancer of the rectum, prostate and lung. The increased incidence of leukaemia appeared in the first 10 years after testicular cancer diagnosis. The excess incidence for gastric cancer, pancreatic cancer, rectal cancer and lung cancer was strongest 10-19 years after testicular cancer, while the relative risk of non-melanoma skin cancer and prostate cancer increased throughout the period of follow-up. The increased incidence of cancer in this cohort is most likely an effect of radiotherapy used for testicular cancer. It is proposed that the different incidence patterns over time after testicular cancer diagnosis reflect differences in the growth rate of tumours originating in different tissues. PMID- 8471325 TI - Application of a sensitive immunoassay to the study of DNA adducts formed in peripheral blood mononuclear cells of patients undergoing high-dose melphalan therapy. AB - The levels of DNA adducts formed in peripheral blood mononuclear cells of 13 patients undergoing high-dose melphalan therapy were determined 0-24 h after drug administration using a modification of a previously described immunoassay. This assay was validated for DNA extracted from drug-treated cells. Adduct levels in normal mononuclear blood cells 1 h after drug administration correlated well (r = 0.846) with drug dose (expressed as mg/m2) and with area under the curve for plasma levels of melphalan during the first h (r = 0.842). 1 patient sustained a high degree of toxic side-effects from the melphalan treatment and showed a high level of adducts. Plasma cell leukaemia tumour cells from another patient showed a level of adducts approximately six times higher than those in the normal blood cells of the other patients. The levels of DNA adducts in normal peripheral blood mononuclear cells did not change markedly between 1 and 24 h after drug administration. PMID- 8471326 TI - Curability of advanced Burkitt's lymphoma in children by intensive short-term chemotherapy. AB - The treatment programme (regimen I) we designed in 1982 for advanced Burkitt's lymphoma was modified in 1986 as regimen IIA and IIB for patients presenting without or with bone marrow (BM) and/or nervous system involvement, respectively. Following a 5-week course of cytoreductive chemotherapy, including vincristine (VCR), cyclophosphamide (CPM), doxorubicin (DXR), high-dose methotrexate (HDMTX) and intrathecal methotrexate and cytarabine (ARAC), high-dose ARAC and cisplatin were given as a 4-day continuous infusion. Regimen I continued with an additional 3-week course including VCR, CPM, DXR and HDMTX, which was omitted in regimen IIA. In regimen IIB the initial cytoreductive chemotherapy was complemented by adding etoposide and increasing HDMTX doses, and by modifying the high-dose ARAC administration modality and was followed, once the bone marrow had recovered, by ifosfamide that concluded the programme. A total of 44 children (22 in regimen I and 22 in regimens IIA and IIB) were treated, with an overall response rate of 98%. 4 patients died as a result of treatment related complications. Survival, progression-free and event-free survival rates were 73, 70 and 63%, respectively, for regimen I, and 82, 90 and 82%, respectively, for regimen IIA and IIB. A short chemotherapeutic regimen, using alternating phase-specific and non-specific agents, is able to cure the majority of patients with advanced Burkitt's lymphoma. PMID- 8471327 TI - Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study. AB - Between 1984 and 1987, 61 radically resected patients with carcinoma of the pancreas (n = 47) or the papilla of Vater (n = 14) were randomised either into postoperative adjuvant combination chemotherapy (AMF); 5-fluorouracil 500 mg/m2, doxorubicin 40 mg/m2, mitomycin C 6 mg/m2 (n = 30) once every 3 weeks for six cycles, or into a control group (no adjuvant chemotherapy) (n = 31). The median survival in the treatment group was 23 months compared with 11 months (P = 0.02, median test) in the control group, dependent on a survival benefit in the treatment group during the initial 2 years (P = 0.04 generalised Wilcoxon). The long-term prognosis was the same with an identical survival after 2 years (P = 0.10, power = 0.83). The observed 1, 2, 3 and 5-year survivals in the treatment group were 70, 43, 27 and 4% compared with 45, 32, 30 and 8 in the control group. 1 patient succumbed to sepsis probably attributable to chemotherapy. Cardiotoxicity and nephrotoxicity were recorded in 2 patients. These results suggest that adjuvant chemotherapy does postpone the incidence of recurrence in the first 2 years following radical surgery but increased cure rate was not observed. PMID- 8471328 TI - Phase II study of vindesine and dacarbazine with or without non-specific stimulation of the immune system in patients with metastatic melanoma. AB - A single dose of dacarbazine (DTIC), followed by a 5-day intravenous infusion of vindesine (VDS) was administered every 3 weeks to 103 patients with metastatic melanoma. One half of the patients were randomised to receive intravenous methanol extraction residue (MER) of bacillus Calmette-Guerin (BCG) in addition to chemotherapy, on days 7 and 14 of each course. 98 patients were evaluable. The response rates in treatment groups were 16 and 17%, respectively (confidence interval 9-24%). Neither the response rate nor the survival improved when MER was added to chemotherapy. Toxicity was moderate except for a significant granulocytopenia. The combination of DTIC and VDS is not more effective than DTIC alone and has added neurotoxicity. PMID- 8471329 TI - Activity and unexpected lung toxicity of the sequential administration of two alkylating agents--dacarbazine and fotemustine--in patients with melanoma. AB - We report the results and discuss the toxicity of clinical trials based on a single concept: the decrease in O6alkyl DNA alkyltransferase (O6AT) resistance mechanism when a chloroethylating agent is used sequentially after a methylating agent. This decrease in O6AT being dose dependent, several increasing doses of dacarbazine (DTIC) have been tested (400 mg/m2 to 1000 mg/m2 every 4 weeks, 3-4 h before fotemustine (100 mg/m2 intravenously every 4 weeks). These results (mean overall response rate 27%) compared with reference regimes, demonstrate that DTIC is able to increase the alkylating power of fotemustine: same range of response rate with only half of the two drug doses compared to an alternated combination, high activity rate especially in lung metastases (10/42 complete responses + 13/42 partial responses), different pattern for haematotoxicity, and occurrence of a new side-effect: acute lung toxicity as adult respiratory distress syndrome (ARDS). This lung toxicity was totally unexpected since several hundreds of patients had been so far treated with fotemustine as single agent or in other combinations with DTIC without any case of acute or delayed lung toxicity. Prophylactic administration of corticoids was not effective and monitoring of the respiratory function was of no predictive value. Due to the additional depleting effects of DTIC on at least two main defence mechanisms--the O6AT system and cytosolic and/or nuclear glutathione--we suppose that the sequence is able to increase the alkylating power of fotemustine to an excessive extent and/or that the detoxication capacity of the cell against DTIC and/or fotemustine metabolites is overwhelmed. Other depletors of the O6AT activity which do not generate metabolites that compete for the same detoxication pathway as the chloroethylnitrosourea (CENU) metabolites should be tested. PMID- 8471330 TI - The identification of informative parameters in the flow cytometric analysis of breast carcinoma. AB - DNA ploidy and the measurement of proliferation or S-phase fraction are both of prognostic significance in breast cancer, yet clinical use is minimal in the U.K. Immunohistochemistry is, however, used to aid diagnosis, so a panel of antibodies were analysed by flow cytometry to assess their predictive value for prognosis, tumour stage and grade. Of 10 parameters tested on 202 breast tumour samples, tumour cell proliferation and DNA ploidy were the two most informative; cytokeratin staining, natural killer and B-cell infiltration also proved to be of value but there was no prognostic value in measuring tumour infiltrating monocytes, helper/suppressor T-cell ratios, tumour cell reactivity with carcinoembryonic antigen or human milk fat globulin antibodies. For each of the informative parameters, scores numerically weighted towards a poorer prognosis were derived which when combined, correlated with tumour grade, stage and prognosis. Such data interpretation is objective, and can be transposed to other human tumours. PMID- 8471331 TI - Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma. AB - The use of high-dose interleukin-2 (IL2), alone or in association with lymphokine activated killer cells in patients with metastatic renal cell carcinoma (MRCC) results in a 20-25% response rate. However, the toxicity of IL2 is substantial and despite many clinical trials, response rates initially reported have not been improved. The aim of this study was to evaluate a combination of IL2 and gamma interferon (IFN) in MRCC with respect to both efficacy and tolerance. IL2 was given by continuous intravenous infusion at a daily dose of 24 x 10(6) U/m2 for 2 consecutive days during 5 consecutive weeks. Gamma IFN was given subcutaneously at a daily dose of 5 x 10(6) U/m2 on the same days as IL2. 33 patients with MRCC entered the study. Clinical responses were comparable with other published series: 7 patients (21%) achieved partial response, 13 (39%) were stable and 13 had progression, despite therapy. Immunological profile observed with this regimen showed a major increase in natural killer cells which became the predominant lymphocyte population at the end of the therapy. Tolerance was good with 92.5% of the planned doses actually received by the patients. This was reflected by an early discharge from the hospital in 95% of the cycles, increasing acceptability of the regimen by the patients. PMID- 8471332 TI - Tumour necrosis factor-alpha plasma levels after flavone acetic acid administration in man and mouse. AB - Flavone acetic acid (FAA) is a synthetic flavonoid with a remarkable spectrum of anticancer activities in mouse tumours, but with no anticancer activity in humans. The mechanism of action of this drug is complex and involves a tumour vasculature action similar to the effects of tumour necrosis factor (TNF). To assess directly the role of TNF in FAA mechanism of action, this cytokine was assayed in both mouse and human plasma after intravenous administration of the drug. In mouse, a species particularly sensitive to FAA antitumour action, FAA plasma concentrations reached 268 micrograms/ml at 0.5 h and remained high (165 micrograms/ml) at 6 h following the intravenous administration of an anticancer efficacious dose (540 mg/m2). After FAA administration in mouse, TNF activity (L929 mouse cell bioassay) increased to 300 pg/ml TNF-alpha-equivalent at 2 h, reached a maximum concentration of 600 pg/ml at 4 h, and declined thereafter to 220 pg/ml at 6 h. TNF activity in mouse plasma was completely abrogated in the presence of mouse TNF-alpha antibodies. FAA added directly to blank mouse plasma did not show TNF activity. In patients receiving the drug as a 6-h intravenous infusion at doses ranging from 3.6 to 8.1 g/m2, FAA plasma levels ranged from 58 to 449 micrograms/ml at the end of infusion. Human TNF-alpha levels assayed with an immunoradiometric assay were either not detectable or very low (< 25 pg/ml) before FAA administration. At completion of the FAA infusion, TNF-alpha remained near background levels in 20 of the 21 courses. A slight increase in plasma TNF alpha was observed in 1 patient at the 8.1 g/m2 dose level of FAA, from 13 pg/ml before intravenous infusion, to 70 pg/ml at completion of intravenous infusion. Taken together, these data demonstrate a marked interspecies difference with regard to TNF-alpha secretion after FAA treatment, as this cytokine is produced in mice, whereas it is not significantly secreted in pretreated patients. Although the low TNF-alpha levels achieved in mice probably do not explain all of FAA antitumour activity in that species, the observed interspecies difference in TNF-alpha secretion after FAA administration could partly explain the marked difference in FAA antitumour activity observed between mice and humans. PMID- 8471333 TI - Dihydropyrimidine dehydrogenase activity in cancer patients. AB - Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of pyrimidines and fluoropyrimidines. The clinical course of 2 patients with suspected DPD deficiency is described. Both patients had significantly delayed clearance of fluorouracil (5-FU), elevated plasma uracil concentrations, and subsequent lethal toxicity. The prevalence of DPD deficiency in the general population is unknown, but given the large number of cancer patients treated with 5-FU, it may be of great clinical significance. Lymphocytes have been previously shown to be a useful marker of systemic DPD activity. Because DPD activity has not been previously reported in a large population of cancer patients using 5-FU as the substrate, we determined DPD activity in lymphocytes from 66 patients with cancer. DPD activity was determined by a sensitive high performance liquid chromatography method. The mean DPD activity (S.D.) in 66 patients with head and neck cancer was 0.189 (0.071) nomol/min/mg protein with wide interpatient variability (range 0.058-0.357). DPD activity was not correlated to age (r = 0.164, P = 0.188). The mean DPD activity in men [0.192 (0.074)] was not significantly different from that in women [0.172 (0.057); t-test P = 0.418]. Likewise, there was no statistical difference in DPD activity in patients who had not received prior chemotherapy [0.195 (0.066)] to patients receiving one or more cycles of chemotherapy [0.186 (0.074); t-test P = 0.638]. PMID- 8471334 TI - Cervical cancer incidence and mortality trends in Finland and Estonia: a screened vs. an unscreened population. AB - Long term trends in the incidence of and mortality from invasive cervical cancer have been studied in Finland (1953-1987) and Estonia (1968-1987). The analyses are based on the data from the Finnish and Estonian Cancer Registries. An organised nationwide screening programme for cervical cancer was started in Finland in the early 1960s. In Estonia, no cytological screening programme has been introduced, and cervical malignancies are diagnosed in routine gynaecological practice. During 1968-1987, both the incidence of and mortality from cervical cancer were considerably higher in Estonia than in Finland. A decrease has taken place in the cervical cancer incidence and mortality in both countries since the mid-1960s, but whereas in Finland the decrease has been marked, in Estonia it has been less pronounced and levelled off in the 1980s. In 1987, the age-standardised (world population) incidence rate per 100,000 women was 14.0 in Estonia and 3.8 in Finland, and the age-standardised mortality rate was 6.0 and 1.6 per 100,000, respectively. The difference in the incidence of the disease in the two neighbouring countries can be partially attributed to socioeconomic factors. The main reason for the different slopes of the trend curves for cervical cancer is probably the difference in public health policies: an effective mass screening programme is being conducted in Finland but not in Estonia. PMID- 8471335 TI - Isolation of pMGT1: a gene that is repressed by oestrogen and increased by antioestrogens and antiprogestins. AB - In order to isolate additional markers of oestrogen responsiveness in breast cancer and to study the mechanisms associated with the development of endocrine resistance, we have searched for oestrogen regulated genes. Differential hybridisation analysis of a cDNA library prepared from oestrogen-stimulated T-47D cells has led to the isolation of a sequence (pMGT1) whose expression is repressed (up to 8-fold) by oestrogen (10(-9) mol/l) and represents the first down-regulated gene to be identified by this methodology. Further studies of pMGT1 expression in MCF-7 cells has revealed that the pure antioestrogens, ICI164384 (10(-7) mol/l) and ICI182780 (10(-7) mol/l) and the antiprogestin Ru38486 (10(-7) mol/l), increase pMGT1 mRNA levels by approximately 40-50-fold relative to the value seen in cells exposed to oestrogens. Under the same conditions, pS2(pLIV2), a gene which is positively regulated by oestradiol, was almost undetectable. Significantly, both tamoxifen (10(-7) mol/l), and 4 hydroxytamoxifen (10(-7) mol/l), failed to increase pMGT1 mRNA levels. Since cell culture studies have indicated that ICI164384 and ICI182780 are more effective than tamoxifen and 4-hydroxytamoxifen at inhibiting the growth of MCF-7 cells by mechanisms that lower their viability and sensitivity to growth factors, it is feasible that pMGT1 plays a central role in mediating these events and instigating pathways associated with cell death. PMID- 8471336 TI - Black (air-cured) and blond (flue-cured) tobacco and cancer risk. III: Oesophageal cancer. AB - Relative risks of oesophageal cancer for smoking were higher in communities smoking mainly black tobacco, when compared with results from populations comprising mainly users of blond tobacco. Also, hand-rolled cigarette smoking, which could be considered as a proxy indicator of black tobacco smoking, was also associated with higher risk of oesophageal cancer, in comparison with the use of commercial (manufactured) cigarettes. Finally, the use of pipes and cigars showed odds ratios of higher magnitude than those associated with cigarettes. This indirect evidence of a higher risk of oesophageal cancer due to the use of black products was confirmed in three recent hospital-based case-control studies. These investigations were able to compare the effect of both types of tobacco; relative risks for black tobacco were two to three times higher than risks associated with blond tobacco smoking, after controlling for major potential confounders. Laboratory evidence suggests that swallowing tobacco condensates could be a major risk factor for oesophageal cancer. Also, the higher content of tobacco-specific N-nitroso compounds in black tobacco, including organospecific substances, could explain its higher carcinogenic effect on the oesophageal mucosa. PMID- 8471337 TI - Economic evaluation and quality of life assessments in cancer clinical trials: the CHART Trial. AB - Arguments are being made more frequently to incorporate economic evaluations and quality of life assessments into clinical trials. Using a randomised, multicentre, phase 3 cancer clinical trial as an example, this paper outlines the importance of including such assessments; the practical considerations associated with the design of such trials; the methods for collecting such data; and, how such data can be used. Finally, it is emphasised that the anticipated benefits of collecting data relating to resource use and quality of life should outweigh the associated costs to research funding organisations. PMID- 8471338 TI - Adjuvant treatment in the curative management of rectal cancer: a critical review of the results of clinical randomised trials. AB - A critical analysis of the results of randomised studies on adjuvant rectal cancer led to a different interpretation than given by the 1990 National Institutes of Health (NIH) conference which concluded that combined postoperative chemotherapy and radiotherapy resulted in increased local control and survival in stage II and III patients. We think there is not as yet indisputable evidence for the use of such combination postoperatively. Furthermore, this approach resulted in increased toxicity and was only consistent with moderate compliance. Conversely, preoperative radiotherapy, which was not even mentioned in the conclusions and recommendations of the NIH consensus conference, definitely increases local control and should now be proposed as standard initial treatment in T3T4 resectable rectal cancer. Moreover, preoperative concomitant chemotherapy is an attractive area for clinical trials. PMID- 8471339 TI - Intermittent continuous intravenous infusion of 5-fluorouracil; a useful approach in disseminated colorectal cancer? PMID- 8471340 TI - Plasma beta-endorphin levels in patients with gynaecological malignancies. PMID- 8471341 TI - Effect of cisplatin on erythropoietin and iron changes. PMID- 8471342 TI - Phase II study of oral miltefosine in patients with squamous cell head and neck cancer. PMID- 8471343 TI - Computer tomography (CT) in the diagnosis and staging of cancer of the penis. PMID- 8471344 TI - Continuing medical education in the United States: a critique. PMID- 8471345 TI - Recent developments in distance learning. PMID- 8471346 TI - [Effect of catalase on acute experimental pancreatitis in rats]. AB - Oxygen free radicals are highly toxic end products of the cellular oxidative metabolism that are scavenged by antioxidative systems such as superoxide dismutase and catalase. Previous studies have suggested that oxygen free radicals may play a role in the pathophysiology of acute pancreatitis. The present study was designed to determine the effect of catalase on experimental acute pancreatitis in the rat. Rats were given either saline or enterokinase by the intraductal pancreatic route. Catalase was given intraperitoneally at doses of 80, 160 and 320 mg/kg. Administration of saline resulted in mild acute pancreatitis. In contrast, administration of enterokinase resulted in oedema, haemorrhage and necrosis of the pancreas. Catalase had no effect when given at 80 mg/kg; at 160 mg/kg, an improvement at the ultrastructural level was noted, whereas at 320 mg/kg, a change in serum calcium level was found. Our studies suggest that intraperitoneal administration of catalase slightly improves the outcome of experimental acute pancreatitis in the rat. PMID- 8471347 TI - [Emphysematous cholecystitis: percutaneous treatment]. AB - We present two patients with emphysematous cholecystitis treated successfully by means of percutaneous cholecystostomy. We emphasize the high mortality rate of the disease, and the good response achieved with the percutaneous technique, as well as the low complication rate of the procedure. PMID- 8471348 TI - [Cytomorphologic characteristics of esophageal carcinosarcoma (pseudosarcoma)]. AB - We report a case of carcinosarcoma or pseudosarcoma of the esophagus, diagnosed through biopsy and endoscopic brush. We also describe several histogenetics hypothesis about this infrequent neoplasm and the difficulty of its diagnosis by means of endoscopy. We emphasize the endoscopic brush positivity and the description of its cytologic characteristics. PMID- 8471349 TI - [Post-radiation enteritis: double jejuno-colic stenosis]. AB - Radiation enteritis is a common complication in patients receiving radiotherapy as a part of the treatment of abdominal malignancies. We report the case of a 57 year male patient with a renal carcinoma, who received radiotherapy and developed a double stenosis of the jejunum and the colon ten years later. He had to be treated surgically with resection of the affected segments. We would like to stress the possibility of this complication in patients who are to be treated with radiotherapy. PMID- 8471350 TI - [Eosinophilic enteritis with mucosal predominance and with a 4 years' course]. AB - We report a case of eosinophilic enteritis without eosinophilia in a 42-year-old woman with symptoms presumably due to the disease since her childhood. We comment the clinical evolution after surgery and some anatomo-clinico and management features of this rare entity. PMID- 8471351 TI - [Massive lower digestive hemorrhage caused by jejunal cavernous hemangioma detected with scintigraphy]. AB - We report the case of a patient who needed urgent surgical assistance because of massive lower gastrointestinal hemorrhage secondary to a jejunal angiodysplasia (cavernous hemangioma). These lesions are a rare cause of gastrointestinal bleeding of obscure origin. The use of preoperative diagnostic techniques such as oral fiber-optic endoscopy, barium intestinal studies and scintigraphy have little value when the origin of lower gastrointestinal bleeding is in the small bowel. The best yield is obtained with celiac or superior mesenteric angiography. There are some cases in which only an exploratory surgical laparotomy is useful for the diagnostic supported by intraoperative enteroscopy guided by the surgeon. PMID- 8471352 TI - [Cecal hernia through the Winslow's hiatus]. AB - A new case of cecal herniation through the foramen of Winslow is reported in a 67 year-old woman, preoperatively diagnosed by water-soluble contrast enema. Herniation through Winslow's foramen is an uncommon variety of internal hernias. Of 144 cases reported up to 1991 in the world literature, the cecum was involved in only 25-30%; and less than 10% of these were radiologically diagnosed before surgery. PMID- 8471353 TI - [Spontaneous hematoma of the transverse mesocolon]. AB - A case of spontaneous rupture of an aneurysm of a colic artery is presented. A large hematoma in the transverse mesocolon was found. The case is interesting because of its rarity and its preoperative angiographic diagnosis. PMID- 8471354 TI - [Retroperitoneal hematoma secondary to anticoagulation treatment as a cause of abdominal pain]. AB - Retroperitoneal haematoma during anticoagulant therapy is a rare cause of abdominal pain. Over the past five years, five cases of retroperitoneal haemorrhage, two of them due to heparin and three to oral anticoagulant, were diagnosed in our hospital. All patients presented with abdominal pain and a mass. The authors conclude that a high degree of suspicion is mandatory when patients on anticoagulant therapy present with abdominal pain. PMID- 8471355 TI - [Severe colitis caused by multiresistant Salmonella non-typhi]. PMID- 8471356 TI - [Jejunal perforation caused by vegetal foreign body]. PMID- 8471357 TI - [Hepatitis caused by droxicam]. PMID- 8471358 TI - [A sonographic technique for the diagnosis of chronic non-lithiasic cholecystopathy]. PMID- 8471359 TI - [Stercoral perforation of the sigmoid related with barium ingestion]. PMID- 8471360 TI - [Prevalence of gastroesophageal reflux in patients with primary motor disorder of the esophagus treated with endoscopic pneumatic dilatation]. AB - The prevalence of gastroesophageal reflux after successful pneumatic dilatation was investigated in 30 patients with primary esophageal motor disorder. After a median follow-up period of 377 days, three patients presented symptoms of acid reflux and five patients had endoscopic esophagitis (grade I, 3 patients; grade II, one patient; and grade III, one patient). Ambulatory 24 hr. esophageal pH monitoring was positive in 20% and 30% of the patients compared to our normal values and to those from other series from the literature, respectively. The concordance between pH results and symptoms and/or endoscopic esophagitis was very low. It is concluded that 24 hr. esophageal pH monitoring is frequently abnormal after pneumatic dilatation, but its clinical significance is low, because very few patients have symptoms and/or severe esophagitis. PMID- 8471361 TI - [Determination of the tumor marker CA 72-4 in gastric carcinoma]. AB - In this study, the authors determined the sensitivity and specificity of the new tumor marker CA 72-4 in detecting adenocarcinoma of the stomach. CA 72-4 serum levels were investigated in 279 patients consisting of: 100 control subjects, 88 patients with benign gastrointestinal disease and 91 patients with gastrointestinal cancer (31 with gastric cancer). We used a cut-off of 5 U/ml. The specificity of CA 72-4 was 91% and the sensitivity was 68%. Highest levels of CA 72-4 were found in patients with more advanced tumor (stages III-IV) and four of 5 patients with stage I had elevated levels of this tumor marker. These findings suggest that the use of serum CA 72-4 measurements may be more useful than other tumor markers in the diagnosis, prognosis and detection of recurrence in patients with gastric cancer. Although CA 72-4 can be elevated in other gastrointestinal adenocarcinomas, it can be useful in alerting the clinician to the possible presence of an intraabdominal neoplasm. PMID- 8471362 TI - [Percutaneous endoscopic feeding gastrostomy. Initial experience with 6 cases]. AB - Over the past two years we have performed percutaneous endoscopic feeding gastrostomy (PEFG) in 5 patients, 4 males and 1 female, aged 42 to 89. All of them suffered from either incurable or severe illness which prevented their oral feeding. PEFG was performed following the method described by Gauderer and Ponsky or traction method. Only in one case it was difficult to perform and in another case a second PEFG was needed because of unintentional catheter extraction. PEFG allowed an adequate feeding in all of the patients until their death due to underlying disorder or to other causes during the follow-up period. The complications found included ascites infection in a patient with cirrhosis and pneumoperitoneum which resolved spontaneously in another case. No mortality was observed related to the procedure. PMID- 8471363 TI - Why not model physiologically? PMID- 8471364 TI - Synergy and isoboles. PMID- 8471365 TI - A physiological model for the distribution of injected agents, with special reference to pethidine. AB - The model is based on Mapleson's Model P for inhaled anaesthetics, but has compartments for lungs, peripheral shunt, kidneys, portal bed, liver, other viscera, muscle, other lean, fat, brain, i.m. injection site and for various blood "pools". Intracellular and extracellular fluids are represented separately in each compartment and in blood. In each fluid, four forms of the agent are distinguished: unionized dissolved in water ("standard" form), ionized dissolved in water, unionized dissolved in lipid, and bound to protein. Equations define the equilibrium between these four forms in any one fluid and between blood and tissue. After changing two of the more uncertain numbers in the quantification for pethidine, good agreement was obtained between computed and published venous concentrations after single i.v. and i.m. injections, continuous i.v. infusions and repeated i.m. injections. The model can be used to make a wide variety of "what if" predictions. PMID- 8471366 TI - Effect on lung volumes of oxygen concentration when breathing is restricted. AB - We have examined the effect of the fractional concentration of nitrogen (FIN2) on the decrease in lung volumes which occurs during restricted breathing with oxygen nitrogen mixtures. Conscious human subjects breathed one of five gas mixtures of oxygen and nitrogen for 15 min on each of five occasions. For the final 5 min of each 15-min period, functional residual capacity (FRC) was reduced by one tidal volume, by external pressurization. After return to normal breathing, the subjects showed a statistically significant decrease in FRC and residual volume (RV), which became larger as FIO2 increased from 30% to 100%. This reduction in lung volumes was resistant to early reexpansion. The maximum decrease in both FRC and RV was found with 100% oxygen, and was 10% of the control lung volumes. The use of a mixture of 75% nitrogen and 25% oxygen prevented this decrease in lung volumes. Nitrogen 50% reduced the decrease in FRC, but did not affect the decrease in RV. The difference in effect on lung volumes between FIO2 25% and 30% was statistically significant, indicating a watershed area for FIN2 between 70% and 75%. PMID- 8471367 TI - Effects of PEEP on dynamic hyperinflation in patients with airflow limitation. AB - We have studied the effects of extrinsically applied PEEP (PEEPe) and intrinsic PEEP (PEEPi) on lung volume and peak airway pressure (Paw,peak) in 10 patients with airflow limitation during mechanical ventilation. PEEPe was applied in 2-4 cm H2O increments until values greater than PEEPi were reached. Total lung hyperinflation was quantified by measuring the expired volume resulting from deflation (starting at end inspiration) until cessation of expiratory flow. The previous expired tidal volume was subtracted from this volume to obtain the change in functional residual capacity (delta FRC), the hyperinflation resulting from PEEPi and PEEPe. PEEPi (0.49-1.66 kPa) was demonstrated in all patients before the application of PEEPe and correlated with delta FRC (r = 0.71), with delta FRC increasing by 582 ml/kPa PEEPi (P < 0.05). PEEPe at pressures less than PEEPi increased delta FRC by (mean) 186 (SEM) 34 ml/kPa PEEPe (P < 0.05) and increased Paw,peak by 0.6 (0.12) kPa/kPa PEEPe (P < 0.05). In contrast, PEEPe at pressures greater than PEEPi, increased delta FRC by 695 (128) ml/kPa PEEPe (P < 0.05) and Paw,peak by 1.8 (0.26) kPa/kPa PEEPe. We conclude that PEEPe may be applied cautiously at values less than PEEPi when clinically indicated, but the application of PEEPe at values greater than PEEPi may substantially aggravate lung hyperinflation. PMID- 8471368 TI - Minimum alveolar concentration of sevoflurane in elderly patients. AB - We have determined the minimum alveolar concentration (MAC) for sevoflurane in elderly patients (mean age 71.4 yr). MAC was found to be 1.48 (SEM 0.08)%, which is smaller than the values for children and adults. The magnitude of the change in MAC with age is similar to that for halothane and isoflurane. The calculated anesthetic ED95 for preventing 95% of patients from moving was 1.98%. PMID- 8471369 TI - Clinical and radiological comparison of perivascular and transarterial techniques of axillary brachial plexus block. AB - The perivascular technique of axillary brachial plexus block results in incomplete block of radial and musculocutaneous nerves in 10-20% of patients. With the transarterial technique and a large dose of mepivacaine, success rates of 99% have been reported. We have compared the clinical efficacy of these techniques in 50 patients using 1% mepivacaine 45 ml with adrenaline. If required, the block was supplemented with additional blocks of single nerves or i.v. alfentanil. Additionally, eight patients in each group were studied with computed tomography after contrast medium was added to 0.5% bupivacaine 40 ml. There were no statistically significant differences in sensory or motor block between the groups at 20 min or in the plasma concentrations of mepivacaine measured 0-45 min after injection. In the CT scans, both proximal and distal spread of the contrast medium were more common after perivascular than after transarterial block. The distribution of the contrast medium was not related to the efficacy of the block. PMID- 8471370 TI - Improvement in i.v. regional anaesthesia by re-exsanguination before surgery. AB - A modification of an i.v. regional anaesthesia (IVRA) technique is described in which the arm is re-exsanguinated before surgery (re-IVRA). IVRA and re-IVRA were compared for quality of operative field, sensory and motor block, quality of analgesia and blood concentrations of prilocaine, lignocaine and mepivacaine in a double-blind study in 120 patients undergoing hand surgery. Re-IVRA provided a significantly better surgical field without affecting sensory or motor block. Re exsanguination improved tolerance of the tourniquet. Plasma concentrations in the re-IVRA group showed some increases, but these were not in the toxic range. PMID- 8471371 TI - Pharmacokinetics of flumazenil and midazolam. AB - We have studied simultaneously the pharmacokinetics of flumazenil and midazolam in 12 healthy Chinese children, aged 5-9 yr, undergoing circumcision. Two hours before operation each patient received midazolam 0.5 mg kg-1 orally for premedication and 0.5 mg kg-1 i.v. during induction. Six minutes after cessation of anaesthesia, a bolus of flumazenil 10 micrograms kg-1 was given i.v., followed by an infusion of flumazenil at 5 micrograms kg-1 min-1 which was maintained until the child could identify himself. Midazolam data were consistent with a three-compartment model with a mean (SD) elimination half-life of 107 (30) min, total body clearance of 15.4 (3.2) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.9 (0.6) litre kg-1. Flumazenil data were best interpreted by a monoexponential function, with a mean terminal elimination half life of 35.3 (13.8) min, a total plasma clearance of 20.6 (6.9) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.0 (0.2) litre kg-1. No unchanged midazolam was detected in the 24-h urine sample, but 5.8-13.8% of the flumazenil dose was recovered unchanged. At the time of self identification, 4.5 (1.4) min after flumazenil administration, the mean plasma concentrations of midazolam and flumazenil were 163.1 (43.7) and 29.9 (16.1) ng ml-1, respectively. PMID- 8471372 TI - Diclofenac and ketoprofen for pain treatment after elective caesarean section. AB - We have studied the effect of a constant infusion of diclofenac 150 mg/24 h, ketoprofen 200 mg/24 h or placebo on postoperative pain after elective Caesarean section performed under spinal or extradural block in 90 patients in a prospective, randomized and double-blind study. During the first 24 h after operation, patients in the treatment groups were more comfortable than the placebo group (P < 0.005); the diclofenac group needed a mean of oxycodone 21.6 mg/24 h and the ketoprofen group 21.2 mg/24 h, compared with 38.3 mg/24 in the placebo group (P < 0.001); the mean time to the first injection of oxycodone was 270.5 min in the diclofenac group, 270.2 min in the ketoprofen group and 161.2 min in the placebo group (P < 0.001). During the first 24 h after operation, the temperature increased in the control group by 0.7 degrees C compared with 0.1 degrees C in the diclofenac group and 0.3 degrees C in the ketoprofen group. One patient in the diclofenac group was eliminated from the study because of uterine relaxation during the first 30 min after start of the drug infusion; this improved after cessation of diclofenac and infusion of sulprostone. There were no other serious side effects. PMID- 8471373 TI - Preoperative indomethacin for pain relief after thoracotomy: comparison with postoperative indomethacin. AB - Indomethacin commenced before operation was compared with postoperative indomethacin administration for pain relief in patients after elective thoracic surgery. In addition to indomethacin, all patients received i.v. opioids titrated to their individual requirements. There was no significant difference between the two groups in quality of pain relief, in cumulative opioid requirement or in the incidence of adverse effects. The quality of pain relief compared well with previous similar studies using this technique. PMID- 8471374 TI - Effects of surgical stimulation on autonomic reflex function: assessment by changes in heart rate variability. AB - Analysis of small oscillations in heart rate (known as heart rate variability or HRV) associated with the activity of homeostatic reflexes can provide a noninvasive measure of autonomic reflex function. We have investigated the effects of surgical stimulation on autonomic reflex function by assessment of changes in HRV. Healthy female patients undergoing laparoscopic tubal ligation were anaesthetized with either thiopentone-nitrous oxide-isoflurane (group I; n = 13) or continuous propofol infusion (group P; n = 13). Power spectral measurements of HRV (HRVtot = total HRV power; %HRVlo = percent of HRV power in the low frequency range) were obtained at the following times; control; before incision; after incision (3 min, 10 min and before skin closure). Compared with control values, measurements of HRVtot before incision were reduced significantly in both groups (group P: 16 (SEM 3)% of control; group I: 2.5 (0.7)% of control). With surgical stimulation, mean HRVtot in group P was restored to 55 (13)% of control (P < 0.01 compared with measurement before incision), whereas mean HRVtot in group I remained at less than 4% of control (ns). %HRVlo increased also in group P, from 49 (7)% to 75(3)% (P < 0.05), consistent with a shift in sympathetic-parasympathetic balance towards sympathetic dominance. These results suggest that surgical stimulation may have significant effects on the autonomic reflexes mediating HRV, and that such effects vary with anesthetic technique. PMID- 8471375 TI - Haemodynamic and catecholamine responses to induction of anaesthesia and tracheal intubation: comparison between propofol and thiopentone. AB - We have studied the haemodynamic changes, QT intervals and catecholamine responses to induction of anaesthesia and tracheal intubation in 24 ASA I patients allocated randomly to receive either propofol 2.5 mg kg-1 or thiopentone 5 mg kg-1 over 60 s. After disappearance of the eyelash reflex, the lungs were ventilated with 100% oxygen for 3 min. The trachea was intubated after administration of vecuronium. With thiopentone, heart rate (HR) was greater than with propofol before intubation (P < 0.05). During induction, systolic (SAP) and diastolic arterial pressure (DAP) decreased more with propofol than with thiopentone. The QT interval was prolonged only during induction with thiopentone. In both groups, HR, SAP, DAP and the QT were increased in response to intubation (P < 0.001). The SAP and QT interval responses to intubation were significantly greater with thiopentone than with propofol (P < 0.05). One patient in the thiopentone group with a significantly prolonged QT interval had episodes of bigeminy and ventricular tachycardia. In both groups, concentrations of noradrenaline in mixed venous plasma increased after intubation (P < 0.001). Concentrations of adrenaline increased after intubation only in the thiopentone group (P < 0.001). PMID- 8471376 TI - Plasma catecholamines and neonatal condition after induction of anaesthesia with propofol or thiopentone at caesarean section. AB - Increased maternal sympathetic nervous system activity may decrease placental perfusion and cause adverse neonatal effects. We have studied the catecholamine response and neonatal outcome in Chinese patients with uncomplicated, singleton pregnancies undergoing Caesarean section. Anaesthesia was induced with thiopentone 4 mg kg-1 (n = 32) or propofol 2 mg kg-1 (n = 30) followed by suxamethonium. Laryngoscopy was performed after 1 min and tracheal intubation completed by 2 min. Anaesthesia was continued with atracurium, nitrous oxide and isoflurane. Maternal venous blood samples were taken at 0, 1, 2, 3, 4 min and at delivery for assay of catecholamines. The increase from baseline values in mean arterial pressure after tracheal intubation was greater in the thiopentone group (29 (SD 15) mm Hg) compared with the propofol group (18 (14) mm Hg) (P < 0.01). The concentrations of noradrenaline and adrenaline increased in both groups after tracheal intubation. Maximum noradrenaline concentrations were greater in the thiopentone group (413 (177) pg ml-1) compared with the propofol group (333 (108) pg ml-1) (P < 0.05), but there were no differences between groups in adrenaline concentrations. Neonatal Apgar scores, neurobehavioural testing and umbilical catecholamine, blood-gas tension and oxygen content analysis were similar between groups. Propofol attenuated the hypertensive and catecholamine response associated with laryngoscopy and tracheal intubation but there was no improvement in neonatal outcome. PMID- 8471377 TI - Benzodiazepines and their solvents influence neutrophil granulocyte function. AB - We have examined the effects of commercially available preparations and drug-free solvents of diazepam (Valium, Diazepam-Lipuro) and midazolam (Dormicum) by N formylmethionyl-leucylphenylalanine (FMLP)- and zymosan-induced polymorphonuclear cell (PMN) chemiluminescence and in a cell-free chemiluminescence system. In the case of Valium, drug-free solvent and diazepam suppressed PMN chemiluminescence. With Diazepam-Lipuro, the solvent stimulated and diazepam inhibited PMN chemiluminescence. With midazolam (Dormicum), only the active drug depressed PMN chemiluminescence. FMLP-induced PMN chemiluminescence was depressed 10-100 fold more by diazepam and midazolam than zymosan-induced chemiluminescence. PMID- 8471378 TI - IV bolus administration of subconvulsive doses of lignocaine to conscious sheep: myocardial pharmacokinetics. AB - Mass balance principles were used to study the myocardial pharmacokinetics of lignocaine in conscious sheep. After i.v. bolus doses of lignocaine 50, 75 or 100 mg, arterial lignocaine concentrations reached a peak in approximately 16 s and these increased linearly with dose. Coronary sinus concentrations reached a peak between 83 and 129 s and the values showed poor relationships with dose. Net myocardial lignocaine uptake lasted for approximately 60 s--this was much shorter than the reported initial distribution half-life of lignocaine. The maximum rate of uptake was proportional to both the dose and the peak arterial lignocaine concentrations. At 15 min, the myocardial lignocaine concentrations were 46 (SD 22)% of their peak values. Pseudo-equilibrium between blood and myocardial lignocaine concentrations was not observed. It is concluded that, despite the myocardium being very well perfused, lignocaine myocardial concentrations were not well represented by blood lignocaine concentrations for at least 15 min. A greater understanding of the determinants of myocardial drug concentrations is required. PMID- 8471379 TI - Influence of cardiac output, injection time and injection volume on the initial mixing of drugs with venous blood after i.v. bolus administration to sheep. AB - The aim of this study was to quantitate factors affecting the initial "peak" of the pulmonary artery (PA) drug concentrations after i.v. bolus drug administration, which is a determinant of the subsequent drug uptake into both the lungs and other well-perfused organs. Indocyanine green (ICG) was used as a marker drug in anaesthetized (1.5% halothane) sheep prepared with an inferior vena cava injection catheter and a large-gauge pulmonary artery blood sampling catheter. For three ranges of cardiac output, 2.5-mg doses of ICG were injected in the following combinations: 10 ml injected over 1, 5 or 10 s; 5 or 25 ml injected over 1 s. On-line PA ICG concentrations were recorded for approximately 60 s using a densitometer. The mean maximum PA ICG concentrations (2-8 mg litre 1), the mean times at which they occurred (7-18 s after injection) and the time lags before ICG was detected in the PA (4-9 s), were inversely related to cardiac output, but linearly related to the time over which the injection was made. The area under the curve of the peak was related inversely to cardiac output only, while the aspect ratio of the peak was related inversely to the time over which the injection was made only. The injectate volume had no effect on any of the measured values. We conclude that, in some circumstances, the rate of injection of drugs with narrow margins of safety should be tailored to the cardiac output of an individual. PMID- 8471380 TI - Hepatotoxicity of volatile anaesthetics. PMID- 8471381 TI - Perioperative management of the obese patient. PMID- 8471382 TI - Studies of gastric content: comparison of two methods. AB - In 20 patients studied under general anaesthesia, we found good agreement between gastric fluid volumes aspirated blindly and total volumes determined by fibreoptic gastroscopy (mean under-estimation 6 ml (22%); range 0-50 ml). Gastric fluid acidity measurements using an electronic pH meter and pH indicator paper also provided results with good agreement (mean difference in pH 0.1; range -0.3 to 0.5). As the use of a standardized blind gastric aspiration technique and pH indicator paper is simpler and provided sufficiently accurate measurements for clinical study purposes, we think this method is preferable. PMID- 8471383 TI - Accumulation of acetone in blood during long-term anaesthesia with closed systems. AB - During closed system anaesthesia with isoflurane, patients with a preoperative increase in blood concentration of acetone (> 10 mg litre-1) had a significantly greater concentration of acetone than patients with an initial normal blood concentration of acetone (P < 0.01). Flushing the closed system with a high flow of fresh gas had no effect on the blood concentration of acetone. Using a large fresh gas flow, there was no increase in blood acetone concentration. Acetone concentrations of about 50 mg litre-1 cause problems such as nausea and vomiting in the postoperative period. These symptoms occurred more frequently after closed system anaesthesia. PMID- 8471384 TI - Test-tube equilibration of volatile anaesthetic concentrations. AB - We have measured concentrations of volatile anaesthetics after injection into test-tube assay solutions. In non-agitated tubes, aqueous anaesthetic concentrations decreased significantly throughout 40 min of incubation. Agitation (20-s vortex) of the tubes decreased the aqueous anaesthetic concentration by approximately 80% from concentrations in non-agitated tubes and resulted in more stable liquid anaesthetic concentrations over time. A decrease of less than 15% occurred between 10 and 50 min of incubation. PMID- 8471385 TI - Delayed presentation of an extradural abscess in a patient with alcohol abuse. AB - Three cases of extradural abscess with delayed presentation after extradural analgesia have been reported previously. The present report describes a patient with alcohol abuse who was treated for 5 days with extradural injections of bupivacaine for pain from multiple rib fractures. The first symptoms of an extradural abscess developed approximately 11 days after removal of the extradural catheter, and definite diagnosis was delayed a further 7 days. PMID- 8471386 TI - Electrode burns during local hyperthermia. AB - A patient presenting with carcinoma of the breast was treated with local hyperthermia by short wave diathermy. During the procedure she suffered severe burns at the site of the ECG electrodes as a result of concentration of the induced current. PMID- 8471387 TI - Comparison of portable emergency ventilators using a lung model. AB - A lung model was used to test the performance of five emergency ventilators (MEDUMAT Elektronik, MEDUMAT Variabel, OSIRIS, OXYLOG and rescuPAC 2DM). The model comprised two glass jars filled with water to suitable compliances and connecting tubes. A resistance (obstruction) was added to one of the "bronchial" tubes in order to simulate a patient with obstructive lung disease. Preset minute volume was compared with measured minute volume and the gas distribution produced by the different ventilators. Acceptable performance was found with the MEDUMAT Elektronik, MEDUMAT Variabel, OSIRIS and OXYLOG ventilators. PMID- 8471388 TI - Pre-emptive analgesia. PMID- 8471389 TI - Effect of nitrous oxide on auditory evoked potentials. PMID- 8471390 TI - Use of lignocaine in ventricular defibrillation? PMID- 8471391 TI - Regurgitation and the laryngeal mask airway. PMID- 8471392 TI - Regurgitation and the laryngeal mask airway. PMID- 8471393 TI - Editorial II--the National Confidential Enquiry into Perioperative Deaths. PMID- 8471394 TI - Propofol and alfentanil mixture. PMID- 8471395 TI - Frequency of damaged coaxial breathing system. PMID- 8471396 TI - Subdural catheterization and cord damage. PMID- 8471397 TI - A great thirst for knowledge. PMID- 8471398 TI - The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials. AB - The proven benefit of aspirin in the secondary prevention of cardiovascular disease and its possible value in primary prevention must be weighted against its potential hazards. This paper is an overview of the gastrointestinal toxicity of aspirin, its most serious complication after intracerebral haemorrhage. Information on toxicity has been drawn only from randomised trials, thus avoiding the potential biases of observational studies. All randomised placebo controlled trials listed in the Anti-platelet Trialists Collaboration where a direct aspirin placebo comparison was possible were included. Twenty-one trials were included, all but one of secondary prevention. There were over 75,000 person years of aspirin exposure. The pooled odds ratios for categories of gastrointestinal bleeding (e.g. haematemesis, melaena) were between 1.5-2.0; fatal bleeds were very rare. The risk of peptic ulcers was 1.3 and of upper gastrointestinal symptoms 1.7. These risks were lower than those found in observational studies. Attributable disease rates are also presented. For haematemesis for example they varied from 0.2-1.0 per 1000 person years. Toxicity was dose related. Aspirin does have significant gastrointestinal toxicity, although this is rarely fatal. More recent work has demonstrated the efficacy of low doses of aspirin (75 mg daily) but there is limited information yet available on its toxicity. PMID- 8471399 TI - The differential effect of aspirin on human platelet activation in aspirin sensitive asthmatics and normal subjects. AB - 1. The in vitro effect of aspirin on platelet aggregation and ATP release induced by platelet activating factor (PAF), arachidonic acid (AA) and collagen (COL) was assessed in 10 aspirin-sensitive (ASP+) asthmatic patients and 10 normal subjects. 2. For PAF, but not AA or COL, both the baseline EC50 and minimum concentration required to produce a maximum response for aggregation were significantly increased in ASP+ asthmatics compared with normal subjects (P < 0.05). Maximum ATP released was greater in ASP+ patients for all agonists but the difference was most significant for PAF (P < 0.025). 3. In ASP+ asthmatics COL induced, but not AA induced, aggregation was less sensitive to inhibition by aspirin compared with normals (P < 0.01). Similarly, analysis of the area under the percent inhibition concentration-response curve showed aspirin to be less effective in inhibiting platelet aggregation induced by PAF in ASP+ asthmatics than in normal subjects (normal subjects: 155 +/- 11 mg% ml-1, ASP+ asthmatics: 115 +/- 19 mg% ml-1; P < 0.05). 4. Regression analysis showed a poor correlation (r = 0.25, P < 0.4933) between the degree of aspirin induced inhibition of ATP release and platelet aggregation induced by PAF in ASP+ asthmatics. 5. The significant differences observed in platelet responses to PAF, COL and to aspirin in ASP+ asthma patients further suggests an abnormality in platelet function exists in this syndrome. PMID- 8471400 TI - The effect of L-leucine on the absorption of levodopa, studied by regional jejunal perfusion in man. AB - 1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L-leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined segment of the proximal small intestine. 2. L-leucine decreased the intestinal absorption of levodopa from 40 +/- 19 to 21 +/- 15% but was without effect on the absorption of antipyrine, benserazide and D-glucose. 3. We confirm that levodopa is absorbed by the active transport system normally responsible for the absorption of large neutral amino acids (LNAA) in humans. Oral absorption by passive diffusion, probably by the paracellular route, might also occur for levodopa in the proximal part of the small intestine. PMID- 8471401 TI - Endogenous digoxin-like immunoreactivity during pregnancy and at birth. AB - 1. We have measured endogenous digoxin-like immunoreactivity (EDLI), in mothers and infants, during normal/pathological pregnancies and at birth. 2. During pregnancy, EDLI was measured in 38 maternal-fetal pairs. At the time of fetal sampling, maternal age was 29 (s.d. 6) years and gestational age was 28 (s.d. 6) weeks. EDLI was present in 13 (34%) mothers and in 27 (71%) fetuses. There was no correlation between maternal and fetal concentrations or between maternal or fetal concentrations and gestational age. 3. EDLI was measured at birth in blood samples from 45 maternal-cord pairs. Maternal age was 29 (s.d. 5) years and gestational age was 39 (s.d. 2) weeks. EDLI was present in 11 (22%) maternal and in 44 (98%) cord samples. The concentrations were significantly higher in cord than in fetal or maternal samples (P < 0.001 in both cases). 4. High cord EDLI concentrations suggest acute synthesis during delivery. Thus, the placental transfer of digoxin calculated from maternal and cord digoxin concentrations at birth may be overestimated. PMID- 8471402 TI - A comparison of the pharmacokinetic and pharmacodynamic properties of quinine and quinidine in healthy Thai males. AB - 1. Eight healthy Thai males, aged 19-27 years, received quinine or quinidine dihydrochloride 10 mg kg-1 body weight by intravenous infusion over 1 h. At least 1 week later, the alternative alkaloid was administered. 2. The terminal elimination half-time of quinidine was shorter than that of quinine (median [range]; 5.7 [5.0-10.0] vs 9.9 [8.8-15.1] h, P < 0.01), the volume of distribution at steady state (Vss) for quinidine was larger than that for quinine (3.5 [2.5-5.6] vs 3.1 [1.8-4.1] 1 kg-1; P = 0.02) and quinidine was less bound to plasma proteins (% free drug: 22.8 [15.4-47.2] vs 9.4 [7.3-15.0]%, P < 0.01). Total clearance was greater for quinidine (7.7 [3.9-11.4] vs 3.4 [1.8-4.6] ml min 1 kg-1, P < 0.01) but not for clearance of unbound drug (32.2 [14.6-50.4] vs 29.9 [20.2-50.9] ml min-1 kg-1 respectively, P > 0.2). 3. Side-effects, including transient hypotension after quinidine in two cases, were mild. 4. Both drugs produced prolongation of the rate-corrected QT interval (QTc), with similar rates of elimination from the cardiac conduction 'effect' compartment (keo; 4.14 [0.03 15.33] h-1 for quinine, 3.74 [1.63-13.14] h-1 for quinidine, P > 0.19). Using a linear concentration-response model, the intercept ('threshold') for quinidine effect was lower than that for quinine (P = 0.004) but the slopes (change in QTc for a given change in free drug concentration) were similar (P = 0.56).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471403 TI - A placebo controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers. AB - 1. The effects of fengabine were compared with those of amitriptyline in healthy elderly volunteers. Doses were administered double-blind and assessments were made before and after ingestion. 2. Psychomotor performance and cognitive ability were measured using tests of choice reaction time, tracking, critical flicker fusion threshold, memory scanning and word recognition. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic data suggest that fengabine may induce its own metabolism following repeated dosing. 4. The findings of this study show that fengabine 200 mg and 400 mg does not produce any noticeable behavioural toxicity in elderly volunteers, in contrast to amitriptyline which had a disruptive effect throughout. PMID- 8471404 TI - The effects of simvastatin and pravastatin on objective and subjective measures of nocturnal sleep: a comparison of two structurally different HMG CoA reductase inhibitors in patients with primary moderate hypercholesterolaemia. AB - 1. It has been suggested that HMG CoA reductase inhibitors which are administered as inactive, lipophilic lactones (e.g. simvastatin) have a greater propensity to evoke nocturnal sleep disturbances than pravastatin, an inhibitor given in the active, hydrophilic, open-acid form. 2. The effects of 4 weeks treatment with equipotent doses of simvastatin (20 mg day-1) and pravastatin (40 mg day-1) have been compared using polysomnography and subjective sleep assessments in a double blind, placebo-controlled, two-period, incomplete block design study involving 24 male patients with primary moderate hypercholesterolaemia (mean LDL cholesterol 5.11 mmol l-1). 3. Analysis of sleep EEG measures relevant to insomnia provided no evidence of significant differences between pravastatin, simvastatin and placebo, except in terms of entries and latency to stage I sleep. The number of entries to stage I sleep was significantly greater after simvastatin treatment than after either pravastatin or placebo (P < 0.05), but by contrast the latency to stage I sleep was significantly prolonged only in the pravastatin group (P < 0.05 vs placebo). 4. Subjective ratings of sleep initiation, maintenance and quality made during and after therapy were not significantly different between the three treatment groups. 5. It appears that the inherent hydrophobicity of simvastatin does not increase the occurrence of sleep disturbances in this patient population at a dose shown to elicit a characteristic hypolipidaemic response. PMID- 8471405 TI - Pharmacokinetics and biochemical efficacy after single and multiple oral administration of losartan, an orally active nonpeptide angiotensin II receptor antagonist, in humans. AB - 1. The pharmacokinetics and biochemical efficacy of losartan, an orally active nonpeptide angiotensin II (AII) receptor antagonist, were evaluated in healthy male volunteers after single and multiple oral administration. 2. Plasma and urinary concentrations of losartan and its active metabolite, E-3174, were determined by a specific high performance liquid chromatographic (h.p.l.c.) method. 3. Plasma concentrations of losartan were proportional to dose over the range of 25 to 200 mg and the terminal half-lives (t1/2,z) ranged from 1.5 to 2.5 h. The mean values of Cmax and AUC0-infinity increased in a dose-dependent manner. 4. Plasma concentrations of E-3174 were higher than those of losartan at all dose levels. The values of Cmax and AUC0-infinity for E-3174 were approximately 2 and 5-8 times higher than those for losartan, respectively. Also the value of t1/2,z was 2 times longer than that of losartan. 5. After multiple dosing for 7 days, the pharmacokinetics of losartan and E-3174 each did not change significantly between day 1 and day 7. 6. Plasma renin activity (PRA) and plasma concentrations of AII increased markedly at all dose levels. Plasma aldosterone levels were slightly reduced, but a similar decrease was also observed with placebo. 7. No clinically significant adverse reaction was observed in any of the volunteers during either study. Blood counts, routine laboratory tests, urine analyses, and electrocardiograms were also not modified by losartan. 8. Losartan appears to be a potent orally active angiotensin II antagonist with a relatively long duration of action. PMID- 8471406 TI - Haemodynamic and hormonal responses to oral enalapril in salt depleted normotensive man. AB - A combination of dietary sodium restriction (40 mmol day-1) and frusemide pretreatment has been used to activate the renin angiotensin system (RAS) in order to characterise the haemodynamic and hormonal responses to enalapril in young normotensives. Enalapril significantly reduced supine blood pressure with a mean maximum fall of 19 +/- 7.6, compared with 6.5 +/- 6.8 mm Hg with placebo. Similar but greater responses were seen in erect blood pressure. Mean maximal plasma ACE inhibition (78 +/- 5.7%) was associated with a significant increase in PRA from 5.2 +/- 2.1 ngAI ml-1 h-1 to a peak of 29.1 +/- 6 ngAI ml-1 h-1. This simple well tolerated regimen produced consistent RAS activation and gave readily measurable falls in blood pressure following enalapril. This model may be used to undertake detailed assessments of ACE inhibition, renin inhibition and angiotensin receptor blockade. PMID- 8471407 TI - The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin. AB - Six healthy male volunteers participated in a two-period, two-treatment study to determine the effect of chronic calcium carbonate administration on ciprofloxacin bioavailability. There was a mean reduction of 40% in Cmax and 43% in AUC when calcium carbonate was administered with ciprofloxacin, compared with ciprofloxacin alone (P < 0.05). There were no changes in either half-life or tmax. It is therefore recommended that patients being treated with ciprofloxacin for serious infections refrain from ingesting calcium supplements. If this is not possible, administration of ciprofloxacin 2 h before ingestion of the supplement is suggested. PMID- 8471408 TI - The reproducibility of quinine bioavailability. AB - Plasma concentrations of quinine were measured in six healthy volunteers after a duplicate administration of 15 mg kg-1 of quinine hydrochloride orally and the administration of 15 mg kg-1 of quinine dihydrochloride as an infusion over 6 h. Quinine absorption rate devised by deconvolution was shown to be complete in less than 2 h. The mean (+/- s.d.) fraction available (F) was 0.76 (0.11) after both oral doses and maximum plasma drug concentrations occurred at 1.90 (0.83) h and 2.00 (0.30) h, respectively. The reproducibility of absorption was high, with a within-subject coefficient of variation of less than 10% for Cmax, AUC and F. Thus, quinine absorption is extensive, fast and reproducible in healthy volunteers. PMID- 8471409 TI - Food intake increases the relative oral bioavailability of vanoxerine. AB - Each of 12 healthy male subjects received single oral doses of 100 mg vanoxerine (GBR 12909), a dopamine reuptake inhibitor with potential antidepressant activity, on three different occasions (fasting, after a low-fat meal and after a high-fat meal) according to a randomized, cross-over design. The mean tmax value increased from 0.82 h after fasting to 1.44 h after a low-fat meal and to 2.46 h after a high-fat meal. Only modest food effects were seen on mean Cmax values (55 nM, 52 nM and 84 nM, after fasting, after the low-fat meal and after the high-fat meal, respectively) but values of AUC up to the last measurable concentration (AUC(0,t)) increased by 76% (from 110 to 194 nM h) after the low-fat meal and by 255% (from 110 to 391 nM h) after the high-fat meal compared with fasting. All of these effects were statistically significant except for the differences in tmax and Cmax between fasting and the low-fat meal. The mechanism of these changes is unclear, but it seems likely that food may lower the first-pass metabolism of vanoxerine, as has been shown for other lipophilic basic drugs. PMID- 8471410 TI - A simple collection method for saliva in children: potential for home monitoring of carbamazepine therapy. AB - We have developed a method of monitoring plasma concentrations of antiepileptic drugs which uses salivary samples, and is suitable for home monitoring in children. To validate the method, paired plasma and saliva samples from 39 children aged between 2 and 15 years were assayed for carbamazepine and its active metabolite, carbamazepine-10,11-epoxide by h.p.l.c. The method uses a gauze-wrapped cotton ball with attached string, to absorb saliva which is then separated using a syringe and plunger. There was no adsorption of CBZ and CBZ-E and they were stable over 1 month in a domestic freezer. Plasma and salivary free CBZ and CBZ-E concentrations were highly correlated (r2 = 0.99 and 0.98, respectively). PMID- 8471411 TI - Morphine glucuronidation in premature neonates. AB - The glucuronidation of morphine was investigated in 10 premature neonates (postnatal age < 24 h at initiation of treatment) following 24 h of therapy (2 h loading infusion, followed by a constant rate infusion). Morphine, morphine-3 glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured in plasma obtained at 24 h in all babies. Plasma concentrations of M3G and M6G correlated significantly with morphine concentration (P < 0.01 in both cases), and with each other (P < 0.001), suggesting that the capacity for morphine glucuronidation in premature neonates is not saturated at the infusion rates used in this study. M3G/morphine and M6G/morphine plasma concentration ratios were independent of morphine infusion rates (P > 0.05) and morphine plasma concentrations (P > 0.05), providing further evidence of linear kinetics. However, M3G/morphine and M6G/morphine plasma concentration ratios increased significantly with increasing birth weight (P < 0.05 in both cases). This probably reflects increase in liver weight with increasing birth weight. Although morphine glucuronidation is deficient in premature neonates, significant concentrations of the respiratory stimulant M3G are achieved rapidly (20% of morphine plasma concentrations at 2 h). At this time, the respiratory depressant M6G could not be detected. PMID- 8471412 TI - Bronchodilating effects of the novel potassium channel opener HOE 234 in human airways in vitro. AB - Bronchodilating effects of the novel potassium channel opener HOE 234 were examined in human bronchi in vitro and compared with those of BRL 38227. HOE 234 produced concentration-dependent relaxations of spontaneous tone and of tone increased by methacholine (10(-6) M), with mean EC50 values of 11 nM and 47 nM, respectively (n = 5). The relaxation produced by HOE 234 was 7 and 3.5 fold more potent than that by BRL 38227 on spontaneous and induced tone, respectively, and was inhibited by glibenclamide (10(-5) M). These results suggest that HOE 234 is a potent bronchodilator which activates ATP-sensitive potassium channels in human airways. PMID- 8471413 TI - Potentiation of the hypoglycaemic response to glipizide in diabetic patients by histamine H2-receptor antagonists. AB - In a randomised placebo controlled study, two groups of six maturity onset diabetic patients stabilised on glipizide were given cimetidine (400 mg) or ranitidine (150 mg) 3 h before a standardised meal. In comparison with placebo, both cimetidine and ranitidine significantly reduced the post-prandial rise in blood glucose by a mean of 40% and 25% respectively producing glucose levels of less than 3 mmol l-1 (lowest 1.5 mmol l-1) in four patients. Both drugs also significantly increased plasma glipizide AUC by approximately 20%. Caution should be exercised when initiating treatment with H2-receptor antagonists in diabetics receiving sulphonylurea hypoglycaemic agents. PMID- 8471414 TI - High clearance of (S)-warfarin in a warfarin-resistant subject. AB - A 30 year old black male required a 60 mg daily dose of warfarin to elicit a therapeutic anticoagulant response (normal warfarin dose 2.5-10 mg day-1; maximum 15 mg day-1). Hereditary warfarin resistance was suspected after compliance, diet, concurrent medication and any gastrointestinal disorder were eliminated as contributory causes. The disposition of vitamin K and vitamin K epoxide was examined in the propositus, his two sisters and 13 control black male subjects. Each subject was given an i.v. bolus dose (5 mg) of vitamin K prior to and after 2 weeks of warfarin therapy (5 mg day-1). The oral clearances of (S)- and (R) warfarin were also measured in each subject during the last day of warfarin therapy. The mean (+/- s.d.) systemic clearance of vitamin K was similar in all subjects before (114 +/- 35 ml min-1) and after (112 +/- 40 ml min-1) warfarin therapy. The mean (+/- s.d.) AUC value for vitamin K epoxide was increased by warfarin treatment (6.5 +/- 5.4 micrograms ml-1 min before and 139 +/- 78 micrograms ml-1 min after) in all subjects. In the propositus, the oral clearance of (S)-warfarin (14.5 ml min-1) and the clearance ratio for (S)/(R)warfarin (2.6) differed by more than 7 standard deviations from the control group (4.3 +/- 1.1 ml min-1 and 1.2 +/- 0.2, respectively). In one sister of the propositus, the stereoselective disposition of warfarin was comparable with that of her brother ((S)-warfarin clearance = 16.2 ml min-1; and (S)/(R)-warfarin clearance ratio = 2.7). PMID- 8471415 TI - The N-demethylation of imipramine correlates with the oxidation of S-mephenytoin (S/R-ratio). A population study. AB - The metabolism of imipramine was investigated in 106 healthy volunteers, all having a sparteine metabolic ratio (MR) of 0.2-0.5 and hence classified as extensive metabolisers. Each subject was given a single oral dose of 25 mg imipramine hydrochloride and blood for assays of imipramine and metabolites was collected 3 h thereafter. The desipramine/imipramine ratio and the 2-OH desipramine/2-OH-imipramine ratio in plasma, reflecting the demethylation of imipramine and 2-OH-imipramine, respectively, showed significant negative correlations with the mephenytoin S/R ratio (Spearman rank correlation) (rs): 0.46, P < 0.00002 and -0.41, P < 0.00002). No correlations were found between the 2-hydroxylation of imipramine or desipramine and the mephenytoin S/R. These findings confirm those of an earlier panel study showing that the demethylation of imipramine and 2-OH-imipramine cosegregates in part with the mephenytoin oxidation polymorphism. PMID- 8471417 TI - International classification of impairments, disabilities, and handicaps. PMID- 8471416 TI - The pharmacokinetics and pharmacodynamics of dermatan sulphate MF701 during haemodialysis for chronic renal failure. AB - Single i.v. bolus doses of dermatan sulphate MF701 were administered before the onset of haemodialysis to patients with chronic renal failure, to prevent clotting in the extracorporeal circuit. Six patients received 2 mg kg-1; six were given 2.5 and 3 mg kg-1; 13 received 4.5 and 6 mg kg-1. Plasma MF701 concentrations (chromogenic assay), activated partial thromboplastin time (APTT) and plasma markers of coagulation and platelet activation (TAT and beta-TG) were measured over 4 or 8 h from the onset of dialysis. The disposition of MF701 was described by a monoexponential function. C(0) and AUC values increased proportionally with dose. Volumes of distribution (approximately 4 l) were dose independent. Half-lives showed a non significant increase with dose (from 2.2 to 3.1 h) and were 2.5-3 times longer than those reported for healthy subjects. There was a significant correlation between plasma MF701 concentration and its effects in prolonging APTT and suppressing TAT and beta-TG generation during dialysis. PMID- 8471418 TI - Global health situation. VI. Health care coverage and resources. PMID- 8471419 TI - Health services research in oncology. PMID- 8471420 TI - The influence of high dose hydroxyurea on the incorporation of 5-iodo-2 deoxyuridine (IUdR) by human bone marrow and tumour cells in vivo. AB - Resistance to cytotoxics precludes the successful treatment of many solid tumours. Inhibition of DNA synthesis in normal tissues with antimetabolites such as hydroxyurea (HU) may be a useful means of improving the selective uptake of toxic thymidine analogues by the relatively resistant tumour cells. HU also inhibits DNA repair by the critical depletion of intracellular deoxyribonucleotides. Twenty-five patients with various malignancies received 5 iodo-2-deoxyuridine (IUdR) 100 mg m-2 as a 20 min i.v. infusion and the uptake of IUdR was determined 1 h later immunocytochemically. Of these patients, 14 received IUdR 23 h from the start of a continuous i.v. infusion of HU (36 g over 36 h). Uptake of IUdR was equally suppressed in bone marrow and tumour aspirates, 0.1% (+/- 0.2%) of marrow precursor cells and 0.5% (+/- 0.4%) of tumour cells respectively, in patients who received HU compared to the uptake of IUdR in 11 patients who were not given HU 6.8% (+/- 1.1%) and 12.2% (+/- 1.8%) respectively. Mean HU plasma concentrations at the time of IUdR administration was 1.7 +/- 0.2 mM. The growth fraction of tumour cells (using Ki67 labelling) was not changed after treatment with HU. It is concluded that (1) since DNA synthesis is effectively inhibited by HU in tumour cells, differential uptake of radiolabelled IUdR by those cells will not be feasible using the current schedule of HU administration, (2) HU may be used as an inhibitor of DNA repair in vivo since the degree of inhibition correlates with that required to inhibit repair experimentally and that (3) Ki67 labelling index is not useful in studying cell kinetics in patients treated with HU. PMID- 8471421 TI - Tumour necrotisation in nude mice xenografts by the reversible protein synthesis inhibitor zilascorb(2H). AB - The deuterated benzaldehyde derivative zilascorb(2H), 5,6-O-benzylidene-d-L ascorbic acid, was administered once daily by i.v. injection in nude mice with grafted tumours of a human malignant melanoma (E.E.) and ovarian carcinoma (OVCAR 3) origins. Like benzaldehyde, zilascorb(2H) has been shown to induce protein synthesis inhibition at otherwise non-toxic doses in cells grown in vitro, and acts reversibly in the sense that protein synthesis returns to normal shortly after removal of the drug. The present data indicate that daily injections with zilascorb(2H) induce a tumour volume growth inhibitory effect in both tumour xenografts studied. Furthermore, from histological examinations of each single tumour it was found that tumours of drug-treated animals, although smaller than those of placebo-treated (i.e. control) animals, had, on average, a higher necrotic fraction than control tumours. Thus, it is concluded that zilascorb(2H) induces tumour necrotisation and not just inhibition of the rate of tumour cell production. Continued measurement of tumour volume after ended treatment with zilascorb(2H) indicated that surviving tumour cells resumed their normal growth rate immediately. The reversibility of the effect induced by this compound, earlier observed in vitro only, is therefore here confirmed to be valid also in two different tumour xenografts in vivo. The present data accords well with the assumption that protein synthesis inhibition is the primary cellular effect of zilascorb(2H) in vivo. We therefore conclude that zilascorb(2H)-induced cancer cell lethality in tumour xenografts probably comes as a secondary consequence of prolonged protein synthesis inhibition. PMID- 8471422 TI - Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion. AB - The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male Wistar rats (n = 80) weighing 70-100 g were given weekly i.p. injections of azaserine (30 mg kg-1 week-1) for 3 consecutive weeks. One week later animals were randomised to receive either PBD or sham PBD and thereafter to receive s.c. injections of either saline or CR-1409 (10 mg kg-1 day 1, 5 days a week). Six months after operation surviving rats were killed as follows: sham + saline 20, PBD + saline 19, sham + CR-1409 14, PBD + CR-1409 11. Cardiac blood was taken for CCK assay and the pancreas was excised for wet weight measurement and quantitative estimation of atypical acinar cell foci (AACF), the precursor of carcinoma. PBD reduced median body weight (3-20% less than shams) but trebled the absolute and relative pancreatic weights (P < 0.001). CR-1409 blunted this adaptive response to PBD, reducing absolute pancreatic weight by 35% (P < 0.005). PBD quadrupled circulating CCK concentrations, regardless of the antagonist treatment. Acidophilic AACF occurred only in rats with PBD. CR-1409 markedly reduced the number of observed acidophilic AACF by 90% (P < 0.001) and the number of foci per pancreas by 93% (P < 0.001). Moreover, CR-1409 reduced the mean focal diameter of each lesion by 18% (P < 0.005), the mean focal volume by 58% (P < 0.05) and the percentage of pancreas occupied by acidophilic foci by 95% (P < 0.001). PBD enhances pancreatic carcinogenesis by causing hypercholecystokininaemia, and CR-1409 largely inhibits this enhancement. PMID- 8471423 TI - Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer. AB - We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma. PMID- 8471424 TI - Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells. AB - The effects of dexamethasone, a synthetic glucocorticoid, and of N,N dimethylformamide on in vitro growth and differentiation and on proto-oncogene expression of human rhabdomyosarcoma cells were studied. RD/18 clone cells (derived from the embryonal rhabdomyosarcoma cell line RD) treated with 100 nM dexamethasone showed an almost complete block of differentiation: about 5% myosin positive cells were observed after 2 weeks of culture in dexamethasone supplemented differentiation medium, compared to 20% of untreated cultures. Dexamethasone also induced a 20-30% growth inhibition and a more flattened morphology. The treatment with N,N-dimethylformamide induced a significantly increased proportion of myosin-positive cells (reaching about 30%) and a 40% growth inhibition. Induction of differentiation inversely correlated with the levels of c-myc proto-oncogene expression: after a 2 week culture dexamethasone treated cells showed the highest c-myc expression and N,N-dimethylformamide treated cells the lowest. Culture conditions per se down-modulated c-erbB1 and up regulated c-jun expression, with no relationship to the differentiation pattern. Other proto-oncogenes were not expressed (c-sis, N-myc, c-mos, c-myb) or were not modulated (c-fos, c-raf). Therefore dexamethasone and N,N-dimethylformamide, both causing a decreased growth rate, showed opposing actions on myogenic differentiation and on c-myc proto-oncogene expression of human rhabdomyosarcoma cells. PMID- 8471425 TI - Increased protein degradation and decreased protein synthesis in skeletal muscle during cancer cachexia. AB - The effects of progressive cachexia on protein metabolism in skeletal muscle has been investigated in mice bearing the MAC16 adenocarcinoma which produces cachexia with tumour burdens of < 1% of the host weight. Weight loss was accompanied by loss of whole body nitrogen in proportion to the overall loss of body mass. Using L-[4-3H]phenylalanine to label proteins in gastrocnemius muscle, a significant depression (60%) in protein synthesis occurred in animals with a weight loss between 15 and 30% accompanied by an increase in protein degradation, which increased with increasing weight loss between 15 and 30%. Muscle degradation in vitro could be achieved by serum from cachectic animals, which appeared to contain a proteolysis-inducing factor. These results suggest that the increased degradation of skeletal muscle seen in this model of cachexia may be due to a circulating proteolysis-inducing factor. PMID- 8471426 TI - Characterisation of UGP and its relationship with beta-core fragment. AB - Urinary gonadotrophin peptide (UGP) was originally identified by immunoassay in the urine of patients with various types of cancer and by immunohistochemistry in human cancers of various histological types. Extracts of normal adult male urine also contained UGP by immunoassay. Purified UGP from different starting material was subjected to high pressure liquid chromatography (HPLC) prior to defining amino acid sequences. Chromatographed UGP after HPLC showed three distinct fractions. The N-terminal sequence of peptide 2 was completely homologous with the beta-core fragment of human chorionic gonadotrophin (hCG) and this was found associated with two smaller peptides. The N-terminal sequence of peptide 1 has not been described previously whilst the N-terminus of peptide 3 that was sequenced showed complete homology with the N-terminal sequence of eosinophil derived neurotoxin and non-secretory ribonuclease. The monoclonal antibodies 2C2 and 6D3 only bind beta core-fragment (peptide 2) whilst the polyclonal (rabbit) antibody AK12 could bind all three peptides. The radioimmunoassay system using AK12 could be inhibited by all three peptides and the immunoradiometric assay although based on a capture antibody (2C2) that only bound peptide 2, had the potential to measure all three peptides (when bound together as UGP) at the second step when 125I-AK12 was introduced as the detector. A specific radioimmunoassay for peptide 3 was generated using 125I-peptide 3 and the AK12 antibody. Beta core-fragment on iso-electric focusing was found to have a pI > 9.5, peptide 3 showed two bands at pI = 3.5 and 3.8 whilst insufficient purified peptide 1 was available to determine its iso-electric point. Bioassay studies on UGP showed that any biological activity could be attributed to trace contamination with hCG. PMID- 8471427 TI - Gallium-67 radiotoxicity in human U937 lymphoma cells. AB - Promising clinical results have been obtained with radiolabeled antibodies in lymphoma patients. The higher uptake by lymphomas of 67Gallium (67Ga) compared with monoclonal antibodies makes selective radiotherapy by the widely available 67Ga appealing. However, the gamma radiation of 67Ga used in scintigraphy is considered to be almost non-toxic to lymphoma cells. However, in addition to photon radiation 67Ga emits low energy Auger electrons and 80-90 keV conversion electrons which could be cytotoxic. The objective of the present study was the assessment of radiotoxicity of 67Ga on a lymphoid cell line: U937. Proliferation (MTT-assay) and clonogenic capacity (CFU-assay) were measured after 3 and 6 days incubation with 10, 20 and 40 microCi ml-1 67Ga. Growth inhibition was 36% after 3 days incubation and 63% after 6 days incubation with 40 microCi 67Ga ml-1. Clonogenic capacity was reduced by 51% after 3 days and 72% after 6 days incubation with 40 microCi ml-1 67Ga. A survival curve showed an initial shoulder and became steeper beyond 200-250 pCi cell-1 (low linear energy transfer type). Iso-effect doses of 67Ga and 90Yttrium (90Y) were determined. The iso-effect dose of 40 microCi 67Ga ml-1 (cumulative dose of conversion electrons 306 cGy) was 2.5 microCi 90Y ml-1 (cumulative dose 494 cGy) and the iso-effect dose of 80 microCi 67Ga ml-1 was 5.0 microCi 90Y/ml. The main cytotoxic effect of 67Ga seems to be induced by the 80 keV conversion electrons. We conclude that the conversion electrons of 67Ga have a cytotoxic effect on U937 cells and that in our experiments a 16-fold higher microCi-dose of 67Ga than of 90Y was needed for the same cytotoxic effect. We believe that 67Ga holds promise for therapeutic use. PMID- 8471428 TI - Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo. AB - The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content. PMID- 8471429 TI - Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oesophageal squamous cell carcinoma in response to epidermal growth factor. AB - We demonstrated that four human oesophageal squamous cell carcinoma cell lines (TE8, TE9, TE10 and TE11) produced matrix metalloproteinase-1 (proMMP-1/tissue collagenase), 2 (ProMMP-2/'type IV collagenase'), 3 (proMMP-3/stromelysin), and 9 (proMMP-9/92-kDa gelatinase) as members of a matrix metalloproteinase (MMP) family, which degrades extracellular matrix macromolecules. Under normal culture conditions, in immunoblot analysis, proMMP-1 of M(r) = 53,00 was detected in one cell line (TE8), proMMP-2 of M(r) = 72,000 in three cell lines (TE9, TE10, and TE11), and proMMP-3 of M(r) = 57,000 in all four cell lines. In addition to these enzymes, in enzymography, a gelatinolytic activity around M(r) = 92-kDa, likely to be proMMP-9, was detected in only one cell line (TE10) under normal culture conditions. When these cell lines were treated with epidermal growth factor (EGF), however, the agent stimulated three cell lines (TE8, TE10 and TE11) to produce proMMP-9 in a dose-dose dependent manner. Oesophageal carcinoma conditioned medium stimulated oesophageal fibroblasts to produce proMMP-1, -2, and -3, suggesting that the interaction between oesophageal carcinoma and stromal fibroblasts also plays a role in the production of MMPs by the latter. Our present study illustrates that oesophageal squamous cell carcinoma produces a variety of MMPs including proMMP-1, -2, -3, and -9 in vitro, suggesting that the ability of MMP production of the tumour may play an important role in its malignant behaviour and that the production of proMMP-9 may be regulated by EGF via overexpression of EGF receptors. PMID- 8471430 TI - The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment. AB - Flunarizine is a class IV calcium channel blocker which increases oxygen delivery to hypoxic regions in solid tumours, exerting a radiosensitising effect in vivo in animal tumour models. Precisely how the drug improves oxygenation is not well understood. We hypothesised that metabolic conditions present within solid tumours reduce red blood cell (RBC) deformability and that flunarizine exerts its in vivo effect by preventing this loss of RBC deformability. A microrheometer was used to compare the viscosity of rat and human RBC suspensions in conditions of hypoxia (pO2 < 10 mmHg), acidic environment (pH 6.8), and elevated lactate concentration (lactate 5 mMol l-1), without or with flunarizine at concentrations of 5, 10, and 50 mg l-1. The effects of flunarizine on RBC density and morphology were also recorded. Hypoxia, low pH, and lactate exposure together increased both human and rat RBC suspension viscosity. Flunarizine at concentrations of 5 and 10 mg l-1 prevented the increases in viscosity. The drug caused dose-dependent shifts toward lower cell density while inducing a characteristic cupped shape (stomatcytic morphology), suggesting a mechanism involving calmodulin inhibition. The results support the hypothesis that flunarizine improves tumour blood flow and oxygenation by enhancing flow properties of RBC's in solid tumours. PMID- 8471431 TI - Cisplatin-DNA damage recognition proteins in human tumour extracts. AB - Enhanced repair of DNA adducts may be a cause of cis-diamminedichloroplatinum(II) resistance in solid malignancies. Binding of specific damage recognition proteins to the sites of DNA damage may be involved in the initial steps of DNA repair, or alternatively may block access of repair proteins to damaged DNA. Proteins which bind specifically to CDDP-modified DNA were identified in cell extracts from human ovarian carcinoma cell lines by two assays, the gel mobility shift assay and the southwestern blot. In the first assay, proteins complexed with CDDP modified oligonucleotide and produced two retarded bands, B1 and B2. The B2 complex was partially purified from an ovarian cell extract by anion exchange FPLC, and was shown to bind to DNA damaged by CDDP but not by transDDP or UV irradiation. Using the southwestern blot, proteins of 97, 48, and 25 kD were identified; each of these bound to CDDP-modified but not undamaged oligonucleotide. The partially purified B2 protein fraction contained both the 97 and the 25 kD damage recognition proteins. A human ovarian carcinoma cell line selected in vitro for CDDP-resistance (OV1P/DDP), which is 5-fold more resistant to CDDP than the parental line (OV1P), showed an increase in binding of the 97 and 48 kD damage recognition proteins compared with the parental line. Twelve ovarian cell lines differed by up to 3-fold in their expression of these proteins, but there was no correlation between the amount of damage recognition protein in a cell extract and the cellular sensitivity to CDDP. Damage recognition proteins were also demonstrated in extracts prepared from biopsies of human ovarian, cervical, and testicular malignancies, but there was no apparent difference in the binding activity in extracts from tumours of different CDDP sensitivity. The functional role of these damage recognition proteins remains to be established. PMID- 8471432 TI - An assessment of the reliability and reproducibility of measurement of potential doubling times (Tpot) in human colorectal cancers. AB - An assessment has been made of the reproducibility of measuring tumour proliferation using in vivo iododeoxyuridine (IUdR) labelling and flow cytometry. The variation that occurs between different institutions (Paterson Institute for Cancer Research, Manchester and the Gray Laboratory, Northwood), different observers and different runs on the same flow cytometer have been measured on 139 samples from 53 patients with colorectal cancer. The results demonstrate that the IUdR technique for measuring tumour proliferation is reproducible. Correlations were seen between measurements of Tpot obtained by different individuals and on separate machines. However, direct comparisons of the measured parameters showed that there were highly significant differences in the values obtained between institutes and observers (P < 0.001). Despite these variations, there were still significant detectable differences in Tpot measurements between individual tumours (P < 0.001). Analysis of the results obtained by running the same samples on two separate occasions on the same machine showed that the technique was highly reproducible and that the staining procedure was stable. Eighty per cent of the samples were similarly assigned to either above or below the median Tpot value, regardless which observer/laboratory combination was utilised. These data suggest that large clinical trials using Tpot should employ a single centre and a single individual to prepare, run and analyse samples. PMID- 8471433 TI - Prognostic significance of cathepsin-D in patients with breast cancer. AB - The expression of the protease cathepsin-D has been evaluated using an immunohistochemical technique with a polyclonal antibody in paraffin-embedded tissue from 359 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and twenty seven patients (35%) have strongly positive, granular staining, 138 (38%) are intermediately stained in the cytoplasm, and in 94 (26%) no staining is observed. There is a strong positive association between expression of cathepsin-D and the presence of tumour in axillary lymph nodes (P < 0.006). Expression of the protease is associated with significantly poorer survival of patients in univariate analysis (P = 0.025); however, this is not independent of other tumour variables. PMID- 8471434 TI - Performance status assessment in cancer patients. An inter-observer variability study. AB - The ECOG Scale of Performance Status (PS) is widely used to quantify the functional status of cancer patients, and is an important factor determining prognosis in a number of malignant conditions. The PS describes the status of symptoms and functions with respect to ambulatory status and need for care. PS 0 means normal activity, PS 1 means some symptoms, but still near fully ambulatory, PS 2 means less than 50%, and PS 3 means more than 50% of daytime in bed, while PS 4 means completely bedridden. An inter-observer variability study of PS assessment has been carried out to evaluate the non-chance agreement among three oncologists rating 100 consecutive cancer patients. Total unanimity was observed in 40 cases, unanimity between two observers in 53 cases, and total disagreement in seven cases. Kappa statistics reveal the ability of the observers compared to change alone and were used to evaluate non-chance agreement. Overall Kappa was 0.44, (95% confidence limits 0.38-0.51). The Kappa for PS 0 was 0.55 (0.44-0.67), while those for PS 1, 2, 3 and four were 0.48 (0.37-0.60), 0.31 (0.19-0.42), 0.43 (0.32-0.55), and 0.33 (0.33-0.45), respectively. If one observer allocated patients to PS 0-2, then another randomly selected observed placed the patients in the same category with a probability of 0.92. For patients with PS 3-4 the probability that the same category would be chosen was 0.82. Overall, the non chance agreement between observers was only moderate, when all ECOG Performance Status groups were considered. However, agreement with regard to allocation of patients to PS 0-2 versus 3-4 was high. This is of interest because this cut-off is often used in clinical studies. PMID- 8471435 TI - Primary gastrointestinal non-Hodgkin's lymphoma: a review of 175 British National Lymphoma Investigation cases. AB - A retrospective analysis was performed upon 175 patients with Non-Hodgkin's Lymphoma involving the gastrointestinal tract and entered into BNLI trials and studies between 1974-1988. Malignant histiocytosis of the intestine (MHI), which was present in 16 patients, was associated with a survival of less than 25% at 18 months, and probably accounted for the poor survival of patients with jejunal involvement. Histopathological evidence of tumour origin from mucosa-associated lymphoid tissue (MALT) was found in 50% of patients with gastric involvement and in 27% of those with intestinal involvement. The overall survival of the series as a whole was 44% at 10 years. Multivariate analysis identified evidence of tumour origin from MALT as the only factor to attain prognostic significance in patients with gastric involvement, and clinical stage and the presence of MHI as the only factors to attain prognostic significance in patients with intestinal involvement. It is suggested that there is a need for a large multicentre prospective study of GIT lymphoma. PMID- 8471436 TI - Frequency of adult T-cell leukaemia/lymphoma and HTLV-I in Ibadan, Nigeria. AB - Sera from a small sample of adult blood donors, healthy school children and patients with lymphoma, leukaemia, non-haematologic cancer, congenital and inflammatory disorders from Ibadan, Nigeria were screened for HTLV-I antibody by an enzyme-linked immunoabsorbent assay and confirmed by investigational Western blot. Seventy-nine of 236 positively screened samples could not be tested for confirmation. Seropositive reactivity was observed in nine of 123 blood donors, and 3 of 46 healthy school children but banding patterns on Western blot were often sparse. Among non-Burkitt's non Hodgkin's lymphoma patients six of 30 were HTLV-I positive including four of four with clinical features of adult T-cell leukaemia (ATL). Other clinical conditions had a frequency of positivity indistinguishable from healthy donors. Western blot patterns ranged from strong with multiple bands, which were uncommon, to those with only p24 and p21 envelope positive which were frequent. Given the relative paucity of clinical ATL and the unusual Western blot patterns the true rate of HTLV-I infection may be lower than estimated. It is possible that a cross-reactive HTLV-I-like virus accounts for this pattern. PMID- 8471437 TI - Carbon-11-methionine and PET in evaluation of treatment response of breast cancer. AB - Uptake of L-methyl-11C-methionine (11C-methionine) in breast cancer metastases was studied with positron emission tomography (PET). Eight patients with soft tissue metastases were studied twice: before the onset of chemotherapy (4), hormonal therapy (3) or radiotherapy (1) and 3-14 weeks later. The radioactivity concentration of the low molecular weight fraction of venous plasma samples separated by fast gel filtration was used as input function. The input corrected uptake rate of 11C-methionine (Ki) in breast cancer metastases before the treatment ranged between 0.035 and 0.186 1 min-1 and the standardised uptake value (SUV) between 2.0 and 11.4. The uptake of 11C-methionine into the metastases decreased when clinical objective stability or regression of the metastases was later obtained and increased in cases where progressive disease was seen during treatment. We conclude that metabolic changes in the amino acid metabolism detected by PET precede the clinical response, and may be of clinical value in predicting the treatment response. PMID- 8471438 TI - Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas. AB - beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival. PMID- 8471439 TI - Chemotherapy and survival in advanced breast cancer: the inclusion of doxorubicin in Cooper type regimens. AB - The value of the inclusion of doxorubicin hydrochloride (dox) in Cooper type regimens in advanced breast cancer was assessed by performing an overview employing summary statistics derived from published papers of randomised clinical trials comparing Cooper type regimens that contain dox with regimens in which dox was replaced by one or more compounds. Trials were selected which published data on survival, time to treatment failure and response rate. This study suggests that dox confers advantages on all of these endpoints and that the size of such benefits needs to be taken into account when deciding whether to use dox. PMID- 8471440 TI - The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group. AB - Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases documented prospectively in the Netherlands. The risk of recurrent disease after primary treatment is very high: in 60% of cases, at least one recurrence is diagnosed within 5 years (95% CI: 58-62%). In patients with a small solitary pTa grade 1 tumour, the 3-year recurrence risk is 37%. In patients with multiple large high grade pT1 tumours, this risk is as high as 77%, despite a significant beneficial effect of adjuvant intravesical chemotherapy. The actuarial risk of disease progression is 10.2% after 3 years (95% CI: 8.6-11.8%). This risk of progression depends on the patient's age at diagnosis, tumour stage, grade, multiplicity and the presence of dysplasia or CIS in random urothelium biopsies. The use of intravesical instillations with chemotherapy or BCG vaccine after TUR does not prevent progressive disease, although this finding is difficult to interpret from a non-randomised study. The 5-year relative survival in patients with superficial TCC of the bladder is 86% (95% CI: 84-88%). PMID- 8471441 TI - The reliability of Cancer Registry records. AB - Data from the Thames Cancer Registry were compared with data independently abstracted from medical records for 466 patients with confirmed cancer of the bladder diagnosed in 1982. High levels of agreement were observed for five continuous variables and for tumour morphology. Data concerning tumour stage did not clearly distinguish superficial from invasive tumours. Cancer registry data were found to be reliable except for tumour stage which may not be clearly documented in clinical records. PMID- 8471442 TI - Does the month of diagnosis affect survival of cancer patients? AB - Some earlier studies based on relatively small data sets have suggested that the month of diagnosis affects survival of breast cancer patients. This phenomenon has been suggested to be attributable to daylight-related hormonal factors. Factors related to the holidays of both the medical personnel and the women themselves might also provide the explanation. In this study we assessed the effect of the month of diagnosis on the survival of 32,807 female breast cancer patients diagnosed in Finland in 1956-1985. Our results indicate that the month of diagnosis is a significant prognostic factor after adjusting for age at diagnosis, period of diagnosis, and stage at diagnosis. The adjusted relative excess risk of death was highest among those diagnosed in July and August, and lowest in March and November, the difference between the lowest and highest risk being 18%. Since colorectal cancer should not have any daylight-related hormone dependent risk determinants, a control cohort of 12,950 women with a diagnosis of colorectal cancer in the same calendar period was studied in a similar way. The survival pattern by month of diagnosis among the colorectal cancer patients was similar to that among breast cancer patients, indicating that general factors associated with the health behaviour of women and the health services (such as holidays) rather than biological factors may cause seasonal variations in survival of cancer patients. PMID- 8471443 TI - Breast-feeding and breast cancer in the offspring. AB - The causation of breast cancer in certain strains of mice by a virus that can be transmitted vertically, through the milk produced during lactation, has led to the hypothesis that a similar phenomenon could exist in humans. There have been laboratory-based studies in humans suggesting that a virus may be involved in the etiology of female breast cancer although other investigations did not support this hypothesis. Descriptive data and epidemiologic evidence of ecologic nature do not indicate a role of lactation in the causation of human breast cancer, but the hypothesis has not been adequately assessed in analytic epidemiologic studies. A nested case-control study undertaken in Sweden to examine the role of prenatal factors on breast cancer risk in the offspring, allowed the evaluation of the importance of breast-feeding in the causation of this disease. Standardised records concerning women born at the Uppsala University Hospital from 1874 to 1954 were linked with invasive breast cancer incident cases, identified through their unique national registration number in the Swedish Cancer Registry during 1958-1990. For each case with breast cancer, the females born to the first three mothers admitted after the case's mother were selected as potential matching controls. Only controls living in Sweden and free from breast cancer until the time of diagnosis of breast cancer in the corresponding case were eventually included in the study. The analysis was based on 458 cases of breast cancer born in singleton pregnancies and 1,197 singleton age- and birth date-matched controls. Breast-feeding was not a significant or suggestive risk factor for breast cancer in the offspring; compared to women who at discharge were wholly or partly breastfed, women who as newborn were not breastfed had a relative risk of breast cancer of 0.97 with 95% confidence interval 0.44-2.17 (P = 0.95). PMID- 8471444 TI - Selected physical activities and the risk of endometrial cancer. AB - The relationship between various indicators of physical activity and endometrial cancer risk was analysed using data of a case-control study conducted in 1988 1991 in Switzerland and Italy on 274 histologically confirmed cases and 572 controls admitted to hospital for acute, non neoplastic, non hormone-related diseases. Using a self-rated assessment of total physical activity, there was a systematic tendency for the cases to report more frequently 'low' or 'very low' physical activity. The relative risks were similar for 'very high' or 'moderately high' physical activity, but increased in the two lowest levels, with point estimates, in various decades of age, between 1.3 and 2.3 for 'moderately low' and over 2.5 for 'very low' physical activity. Although the association was apparently stronger at older ages, all the trends in risk were significant. Allowance for major identified potential distorting factors, including body mass index and a measure of total energy intake, could explain only in part the association, and the inverse trends in risk remained statistically significant. When selected types of physical activity were analysed, no association was observed with climbing stairs or walking, but the risk estimates for the lowest level of activity was over 4 for housework, and between 1.5 and 1.9 for sport and leisure and occupational activity. Thus, the present findings suggest that a moderate or high physical activity is an indicator of reduced endometrial cancer risk, although this observation still requires epidemiologic confirmation and clearer definition from a pathogenic point of view. PMID- 8471445 TI - Receiver operating characteristic (ROC) curve analysis of the tumour markers CEA, CA 50 and CA 242 in pancreatic cancer; results from a prospective study. AB - The serum values of the tumour markers carcinoembryonic antigen (CEA), cancer associated carboanhydrate antigens CA 50 and CA 242 were evaluated in 193 patients with hepatopancreato-biliary diseases by receiver operating characteristic (ROC) curve analysis in order to compare their diagnostic accuracy in pancreatic cancer (n = 26), and to define optimal cut-off levels for the serum values of these tumour markers in the diagnosis of pancreatic cancer. The ROC analysis showed that all marker tests are considerably sensitive (77-81%) at the specificity level of 80%. The CA 242 test was more sensitive than CEA and CA 50 at high specificity levels (> 0.90) but slightly less sensitive at low specificity levels (< 0.60). The CEA test and CA 50 test performed equally well at high and low specificity levels. According to this study, it would seem optimal to use the cut-off level of 4.1 ng ml-1 for CEA, and the level of 137 U ml-1 for CA 50, since they gave a sensitivity of 77% at the specificity levels of 83% and 84%, respectively. For CA 242 the optimal cut-off level was 21 U ml-1, which gave a sensitivity and specificity of 81%. In conclusion, the results of ROC curve analysis suggest that the CA 242 test has an advantage over CEA and CA 50 because of its higher specificity in pancreatic cancer. In addition, it would seem reasonable to use higher cut-off values than what has been recommended for CEA and CA 50 in the diagnosis of pancreatic cancer, but for CA 242 the recommended cut-off level of 20 U ml-1 seems appropriate. PMID- 8471446 TI - Advanced breast cancer: use of resources and cost implications. AB - Little information is currently available on the use of hospital resources and the resulting costs of treating any advanced cancer. Such data may be useful for planning purposes and for calculating the cost effectiveness of measures designed to reduce the incidence of advanced disease (such as the National Breast Screening Programme). A retrospective analysis of the medical records of 50 patients with advanced breast cancer who attended the Guy's Hospital Oncology Unit and who died between October 1988 and December 1990 has therefore been undertaken. For each patient, the duration of in-patient stays and principal indications for admissions were recorded, together with the number of out-patient attendances. Details of endocrine treatment, chemotherapy and radiotherapy were abstracted as were all radiological and laboratory investigations. Costs for each of these activities were calculated. The median duration of advanced disease was 17 months (mean 27 months; range 7 days-12 years). The mean cost of treatment per patients was calculated to be 7,620 pounds (range 317 pounds-27,860 pounds). Mean duration of in-patient stay was 32 days (0-133) and this accounted for 56% of total costs. The large majority (> 80%) of the time spent as an in-patient was for the care of serious illness rather than for specific antitumour treatment. Cytotoxic drugs accounted for 9% of the total cost, compared with 8% for radiotherapy and 13% for laboratory and radiological investigations. PMID- 8471447 TI - Supportive care and the use of relaxation therapy in a district cancer service. AB - The development of a cancer support organisation, CancerCare, for North Lancashire and South Lakeland is described. The use of relaxation therapy is described to illustrate the demand for supportive care. Between January 1990 and 1991, 513 patients, 243 relatives and 143 bereaved were referred to five cancer support nurses. One hundred and sixty-two (32%), 29 (12%) and 49 (34%) respectively, used relaxation therapy. The high demand for supportive care suggests that services should be made available in any district health provider unit. Measures of benefit and better definition of services are required before clear recommendations can be made. PMID- 8471448 TI - Gall and goodwill. PMID- 8471449 TI - Nurses work. Catching the first post. PMID- 8471450 TI - Nurses work. Finished after finals? PMID- 8471451 TI - Laparoscopic cholecystectomy. AB - Advances in surgical technology have enabled the concept of 'keyhole surgery' to become a reality. The author describes the technique of laparoscopic cholecystectomy and the advantages it offers over conventional methods of surgically removing the gall bladder. PMID- 8471452 TI - Ethics: can nurses be effective advocates? AB - Patient advocacy is currently a subject of burning interest in the nursing profession, with encouragement for nurses to assume such a role coming from the United Kingdom Central Council (1) and the government (2). This article questions whether nurses have had sufficient preparation for this role, and looks at factors which may facilitate or impede patient advocacy. PMID- 8471453 TI - Improving input to case conferences. AB - Nursing contributions to case conferences, particularly those concerned with child protection issues, have tended to be inconsistent. Part of the problem has been that there is little advice or guidelines to direct the nurses. This article reports on an initiative in Croydon which attempted to raise the standards of nurse contributions through the use of a specially designed report pack. PMID- 8471454 TI - Minor injury care in the community. AB - This article describes the setting up and running of a nurse-led, community based, minor injuries unit. Initially meeting with resistance from the local health authority, a six month pilot study showed that the clinic could operate effectively to the benefit of the community. The process of setting up the clinic and the type of service it provides are described. PMID- 8471455 TI - Resuscitation: outcomes, ethics and accountability. AB - The third and last part of Nursing Standard's series on resuscitation deals with the difficult issues of outcomes, ethics and responsibility. In particular, the vexed question of when not to resuscitate is aired: statistics show the remarkably poor success rate of cardiopulmonary resuscitation (CPR), which suggests that this invasive and sometimes brutal procedure is carried out inappropriately on individuals who are consequently denied the right to a peaceful death. Doctors and nurses, the author argues, become sensitive to when a life is ending naturally, and should be allowed to restrict the use of CPR to those for whom it is likely to help. PMID- 8471456 TI - Tradimus. Learning isn't shameful. PMID- 8471457 TI - Tradimus. Ward placements: a kick up the assessment. PMID- 8471458 TI - Tradimus. Placements: skill on wheels. PMID- 8471459 TI - Tradimus. International: Spanish practices. PMID- 8471460 TI - Tradimus. Education: practically useless? PMID- 8471461 TI - Tradimus. Professional unity: vive la similarity. PMID- 8471462 TI - Nurses work. Cutbacks: UK snapshot. PMID- 8471463 TI - Just my age? (continuing education credit). AB - Most elderly people lead independent lives. However, those who come into contact with nurses need a continuum of care, from health advice to full nursing care. Health care professionals should not make assumptions based on age and dismiss aches and pains as 'just your age'. Rather, they should assess the individual and provide care accordingly. PMID- 8471464 TI - Black & ethnic minority clients: meeting needs (continuing education credit). AB - No matter where nurses work they are bound to come across some clients from the black and ethnic minority populations whose first language is not English. It is therefore necessary for nurses to understand the different needs of these clients and to develop the skills to provide sensitive and appropriate health care services for them. PMID- 8471465 TI - Unsafe sex and HIV-1 transmission. PMID- 8471466 TI - Pneumonia link to HIV status in drug use. PMID- 8471467 TI - Nurses work. Careers out of control? PMID- 8471468 TI - Nurses work. Help yourself to a job. PMID- 8471469 TI - Nurses work. A community nurse at heart. Interview by Charlotte Alderman. PMID- 8471470 TI - Nurses work. Getting back to work. Interview by Charlotte Alderman. PMID- 8471471 TI - A review of pain assessment tools. AB - Pain assessment and control should be a priority within nursing but pain is often underassessed and unrelieved. Pain is difficult to assess as it is complex and subjective, and assessment is influenced by many factors. A pain assessment tool can be invaluable as it can aid the patient to communicate his or her pain, remove the subjectivity of assessment, and promote a systematic approach. A variety of pain assessment tools have been developed and used in clinical settings with subsequent improvements in assessment. They each have specific attributes, and their place in clinical practice is considered. It is concluded that the use of pain assessment tools is advantageous, and the reasons why they are not used more widely are considered. PMID- 8471472 TI - Monitoring activities in a long-term ward. AB - Moving the emphasis in long-term ward settings from just keeping people clean, dry and fed to providing improvement in their quality of life is a laudable aim, but this article, based on a six-month project, suggests that doing so is not as easy as it might first appear. The authors describe the development of an intervention programme for elderly women in a long-term ward and discuss some of the difficulties encountered in producing positive changes. PMID- 8471473 TI - Ethics: the use and abuse of power in nursing. PMID- 8471474 TI - The role of nurses in health purchasing. AB - This paper considers nurses' responsibilities on giving advice about the purchasing of health care. By outlining the steps in the purchasing cycle, a coherent framework is presented for identifying the specific issues associated with the purchasing of health services by district health authorities (DHAs), and family health service authorities (FHSAs) in England and Wales, and health boards (HBs) in Scotland. Purchasing health is every nurse's business. All registered nurses in the UK have a contribution that they can and should make to ensure that their DHA, HB or FHSA makes the best possible provision for their resident population. PMID- 8471475 TI - Changes to the Care Sector Consortium responsible for National Vocational Qualifications (NVQs) in health and care settings. PMID- 8471476 TI - Write off sisters. PMID- 8471477 TI - The Standard guide to surviving studying. PMID- 8471478 TI - Health promotion goes AWOL. PMID- 8471479 TI - Reassurance on risk of HIV-positive midwife. PMID- 8471480 TI - Ditching the professional face. PMID- 8471481 TI - Maternity care: midwifery is dead. PMID- 8471482 TI - Community care: meaning on the streets. PMID- 8471483 TI - Nurses work. Growing evidence of cuts in services and nursing posts. PMID- 8471484 TI - Prejudice threatens effective HIV nursing. PMID- 8471485 TI - Call to extend vigilance in tuberculosis. PMID- 8471486 TI - Information services: providing a multi-agency approach. PMID- 8471487 TI - Community health: when the taps run dry. PMID- 8471488 TI - Nurses work. Headed for mass unemployment? PMID- 8471489 TI - Nurses work. New roles for nurses. PMID- 8471490 TI - Daphne Heald Research Unit: ten years on. AB - The Daphne Heald Research Unit was set up just over ten years ago to develop the art and science of nursing through research, and to encourage nurses to use research. In the intervening years, four major studies have been published looking at the work of clinical nurse specialists in diabetes and stoma care, nurses' knowledge of sickle cell disorders and management of early discharge after surgery. With three major projects on the way, the Unit is continuing to support the need for rigorous research. PMID- 8471491 TI - Managing headaches in the workplace. AB - Headache may not impose a considerable burden upon the resources of the National Health Service, but it does have a significant impact on work attendance, with up to seven million working days being lost per year because of headache-related problems. The author reviews the problem from the perspective of occupational health nurses, and offers a protocol, based on the investigations carried out in practice-attached migraine clinics, which will assist their assessment of affected employees. PMID- 8471492 TI - Performance related pay and NHS nursing. PMID- 8471494 TI - A&E or the GP? How patients decide. PMID- 8471493 TI - Assessing the risk of pressure sores. AB - This article provides an overview of the basic requirements of a good assessment tool and details the development of three pressure sore risk assessment scales- the Norton score (1), the Waterlow score (2) and the Braden scale (3). The tools described are critically reviewed in relation to their reliability and validity, and conclusions made regarding their usefulness in clinical practice and research. PMID- 8471495 TI - Women's network. Women in public. PMID- 8471496 TI - Health targets off the rails. PMID- 8471497 TI - AIDS focus. AIDS and women on the islands of Zanzibar. PMID- 8471498 TI - AIDS focus. The rehabilitation of people with AIDS. PMID- 8471499 TI - Managing pain in children. Playing monsters and dragons. PMID- 8471501 TI - Managing pain in children. Special care for special babies. PMID- 8471500 TI - Managing pain in children. Pain scales for toddlers. PMID- 8471502 TI - Managing pain in children. Myths in practice. PMID- 8471503 TI - Managing pain in children. Taking action. PMID- 8471504 TI - Managing pain in children. 'Relief only when desperate'. PMID- 8471505 TI - Managing pain in children. APS: a multidisciplinary team. PMID- 8471506 TI - p53 protein expression in benign and malignant skin tumours. AB - The skin affords an excellent model of human carcinogenesis because a variety of lesions from benign tumours to invasive malignancy, with or without metastatic potential, are commonly found, and are accessible to biopsy. To date, few genetic alterations have been observed in skin neoplasia. In this study we have used a recently developed monoclonal antibody (DO7) to examine p53 protein expression in a wide variety of benign and malignant skin lesions. Benign skin lesions were negative, but a significant number of malignant epithelial lesions showed detectable p53; 56% of squamous carcinomas and 42% of basal cell carcinomas were positive. A smaller proportion of dysplastic epithelial lesions were positive (27%), and only 3.6% of malignant melanomas were positive. Thus, although detectable p53 protein is a common occurrence in malignant epithelial lesions, it does not correlate with the malignant phenotype or with metastatic potential. The finding of a lower proportion of positivity in dysplastic lesions, and absence of staining in benign tumours, suggests that p53 mutation may be involved in the progression towards invasive malignancy in human squamous skin lesions. PMID- 8471507 TI - Capillary underperfusion in chronic venous insufficiency: a cause for leg ulceration? AB - Dermal capillaries in the goiter area of the lower leg were examined by video microscopy before and after the administration of intravenous fluorescein in 13 patients with chronic venous insufficiency (CVI) who were at risk of developing leg ulceration, and in 13 normal controls. The influence of posture on capillary perfusion was determined by viewing the same area of skin with the leg in both the supine and dependent positions. Capillary density was lower in patients than in controls, irrespective of the position of the leg (P < 0.01). Fluorescence angiography studies in normal controls showed a reduction in capillary density with dependency (P < 0.01), but patients with CVI showed no significant change. Fluorescence angiography revealed a greater number of capillaries than seen during native capillaroscopy (P < 0.05). The decreased capillary density, and the loss of the postural vasoconstrictor reflex in patients with chronic venous incompetence may play a role in the pathogenesis of ulceration. PMID- 8471508 TI - The effect of compression on venous stasis. AB - Skin blood flow in the lower leg is increased by external compression in standing subjects. This prevents the hypoxia induced by standing. The maximum increase in oxygen tension is seen when the external pressure is 40-50 mmHg. Pressures in the range of those produced by lightweight elastic stockings were found to be ineffective. Our results uphold the commonly held clinical opinion that only compression bandages or strong stockings are effective in the treatment of venous ulcers. External compression when the subject is recumbent causes skin oxygen tension to fall. Uniform external pressure exceeding 10 mmHg should therefore be avoided in the prophylactic treatment of post-operative deep-vein thrombosis. This observation suggests that when the patient is confined to bed, only lightweight stockings are safe in the prophylaxis of post-operative deep-vein thrombosis. PMID- 8471509 TI - Semiquantitative assessment of hirsutism in Dutch women. AB - Many doctors frequently encounter hirsute patients. Quantification of hair growth may be useful for diagnosis and follow-up. To establish the reference range for distribution and density of hair in females, and to determine the regions yielding the best discrimination between normal and hirsute women, we studied the distribution and density of terminal hair on 12 body regions assessed on a scale of 0-4. Prospectively, 81 healthy female volunteers and 71 hirsute patients of child-bearing age and Dutch ancestry, who were not receiving medication, and who had not had a recent pregnancy were studied. The reference hair pattern was established for each body region, and the threshold value yielding the highest sensitivity and specificity to evaluate hirsutism was calculated. None of the women in the reference population displayed a score of more than 1 for chin, upper back, upper abdomen and upper arm, or more than 2 for upper lip, side burns, chest, lower back, lower abdomen, thighs or forearm. The best discrimination between the reference and hirsute populations was obtained with the sum of the scores for four regions: upper lip, chin, lower abdomen and thighs. Independent assessment of hair growth by two investigators revealed excellent agreement. We conclude that a score of more than 1 for chin, upper back, upper abdomen and upper arm, or more than 2 for upper lip, side-burns, chest, lower back, lower abdomen, thighs or forearm is abnormal for Dutch women, and that assessment of hair growth on the upper lip, chin, lower abdomen and thighs is the most suitable way to evaluate hirsutism. PMID- 8471510 TI - Continuous formation of nail along the bed. AB - To resolve the problem of whether nail is formed continuously along the length of the nail bed as well as by the germinal matrix, nail thickness was measured at six anatomical points along the length of 20 normal big toe-nails removed after injury. Nail water content was constant at 9-10% along the nail length, and the nails did not shrink with dehydration. Approximately 79% of nail thickness was contributed by the nail matrix, and 21% by the nail bed. The rate of nail production was constant at 0.13 mm/mm along the lunula and 0.027 mm/mm along the whole bed from the distal lunula to the point of separation at the onychodermal band; the fractional change in linear growth and thickness showed less variation than absolute change. The continuous production of nail by the bed provides a simple biological solution to the problem of attachment of a continuously moving plate. It provides a source of entry of drugs into the distal nail plate, and a rationale for the use of much shorter courses of antifungal drugs than previously believed possible. PMID- 8471511 TI - Anticardiolipin antibodies in Adamantiades-Behcet's disease. AB - Moderately raised levels of circulating anticardiolipin antibodies were found in 14 of 30 patients with active Adamantiades-Behcet's disease (46.7%) who were not receiving treatment. Three patients showed the IgG isotype, nine the IgM isotype, and two had both IgG and IgM isotypes. Statistical analysis, to determine possible correlations between anticardiolipin antibodies and clinical features, and meta-analysis of the data available, were performed. A positive correlation between erythema nodosum and histologically confirmed cutaneous vasculitis and the presence of circulating anticardiolipin antibodies of the IgM isotype was found (P = 0.017 and 0.018, respectively), whereas the IgG isotype did not correlate with any clinical feature. Evaluation of data on other clinical manifestations showed no correlation, either with the IgG or IgM isotypes. In particular, there was no association of circulating anticardiolipin antibodies with the incidence of thrombosis, systemic vasculitis, retinal involvement or neurological features. These results suggest that anticardiolipin antibodies do not play a major pathogenetic role in Adamantiades-Behcet's disease, but they may serve as an additional marker for a risk of the development of cutaneous vasculitis such as erythema nodosum. PMID- 8471512 TI - Clinical and laboratory studies of the photosensitizing potential of norfloxacin, a 4-quinolone broad-spectrum antibiotic. AB - Cutaneous photosensitivity reactions are a consistent although uncommon feature of the fluoroquinolone group of antibiotics, which are related to nalidixic acid. Objective laboratory and clinical data are now routinely required by regulatory bodies for new drugs suspected of being photosensitizers, but no clear recommendations exist. A series of in vitro tests ranging in complexity revealed a UVA-dependent phototoxic potential for the fluoroquinolone norfloxacin similar to that for ciprofloxacin, and less than that of nalidixic acid. Controlled monochromator phototesting, designed to reveal the clinical characteristics, wavelength dependence and severity of cutaneous reactions in normal subjects showed both norfloxacin and ciprofloxacin to have a weak phototoxic potential which clears within 4 weeks of stopping the drug. UVA wavelengths (335 +/- 30 nm; 365 +/- 30 nm) appear most responsible for producing an asymptomatic erythema which is maximal at 24 h. The clinical study differs from those used previously in being blind, containing positive and negative controls, and phototesting after cessation of drug intake. The methodology has the anticipated limitation of failing to detect idiosyncratic photosensitivity responses. PMID- 8471513 TI - Response of psoriasis to psoralen-UVB photochemotherapy. AB - The effect of psoralen in combination with 311 nm (UVB) radiation was studied in five subjects with normal skin and 10 patients with psoriasis involving both forearms. Treatment with oral 8-methoxypsoralen augmented the UVB erythemal response at 6 h after irradiation, but had no effect at 24-72 h. In eight of the nine patients who completed the trial, lesions of psoriasis on the arms treated with psoralen-UVB cleared before lesions on the arms treated with UVB alone. This study has shown that psoralen in combination with UVB has an erythemal effect on normal skin, and a therapeutic effect in psoriasis which is greater than the response to UVB alone. PMID- 8471514 TI - Failure of coconut oil to accelerate psoriasis clearance in narrow-band UVB phototherapy or photochemotherapy. AB - Despite a widely held belief that the use of emollients prior to broad-band UVB irradiation accelerates clearance of psoriasis, only one single-blind controlled study exists in support of this. No similar study has been carried out with photochemotherapy (PUVA) or narrow-band UVB (311-313 nm) phototherapy. As some emollients absorb UV radiation, and thereby inhibit psoriasis clearance, there is a need to identify emollients suitable for pre-irradiation use. Coconut oil may be useful in this respect. In two randomized groups of patients with chronic plaque psoriasis undergoing either routine PUVA (n = 14) or narrow-band UVB phototherapy (n = 15), a single-blind controlled (half-body) study was undertaken to assess the effect of pre-irradiation application of coconut oil. Patients were given PUVA twice weekly, or TL-01 therapy thrice weekly. The initial UV dose was 70% of previously determined minimal phototoxic (MPD) or minimal erythema doses (MED), with 40% incremental steps at each visit (reduced if adverse effects occurred). Psoriasis severity was scored on each side after every three treatments. No significant acceleration of psoriasis clearance was seen in either group. We do not, therefore, recommend the routine use of emollients prior to PUVA or TL-01 therapy when using near erythemogenic irradiation regimens. PMID- 8471515 TI - Results and tissue healing after copper-vapour laser (at 578 nm) treatment of port wine stains and facial telangiectasias. AB - Twenty-four patients with port wine stains (PWS), and 33 patients with facial telangiectasias were treated with a copper-vapour laser (CVL) operating at 578 nm. Good to excellent results were obtained in 52% of PWS and 69% of facial telangiectasias. Enzyme histochemistry revealed vessel-selective damage with energy densities up to 12 J/cm2, but a non-specific coagulation necrosis with higher fluences (> or = 15 J/cm2). With vessel-selective fluences only moderate blanching was obtained in two PWS. All other evaluated patients were treated using non-selective energy densities. Tissue healing was comparable with that after argon laser treatment. The theoretically correct wavelength (578 nm) alone appeared to be no guarantee of vessel-selective damage. The laser employed lacked adequate power (only 1.3 W maximum) to transmit sufficient energy into the tissues in a short exposure time. However, the clinical results confirm the value of the CVL in the treatment of superficial cutaneous angiodysplasias. PMID- 8471516 TI - Light cautery and EMLA in the treatment of chloracne lesions. AB - We report six patients with chloracne, unresponsive to conventional therapy, whose lesions were cleared by treatment with EMLA (eutectic mixture of lignocaine [lidocaine] 25 mg/g and prilocaine 25 mg/g) topical anaesthesia and light cautery. To the best of our knowledge, this form of treatment for chloracne has not previously been reported. PMID- 8471517 TI - Inadequate size of 'negative' clinical trials in dermatology. AB - Fifty-eight clinical trials with negative conclusions, published in three British dermatological journals over the last 4 years, were reviewed to determine the risk of their having missed an effective treatment. All but one of the 44 evaluable trials had a greater than 1 in 10 risk of missing a 25% relative treatment difference (median risk 81%), and 31 of the trials (70%) were so small that they had a greater than 1 in 10 risk of missing a 50% relative treatment difference (median risk 42%). The 'negative' trial result was compatible (within 95% confidence limits) with a 25% beneficial relative treatment effect in 36 studies (82%), and a 50% treatment benefit in 22 studies (50%). Only one study used confidence intervals to describe the main findings, and only three studies (7%) mentioned the basis for sample size estimation at the outset of the study. Of particular concern was that in half (23/44) of the studies there was an incorrect interpretation of the findings. It is worrying to observe such a profusion of clinical trials in dermatology which are too small to answer the questions being posed, especially when this is coupled with misreporting of results. Apart from ethical concerns, many treatments compatible with a considerable treatment benefit may have been erroneously discarded as a result of such studies. We recommend the use of confidence intervals to summarize clinical trial findings, so that readers can quickly decide whether clinically important treatment effects are plausible. PMID- 8471518 TI - Monilethrix: a clinicopathological illustration of a cortical defect. AB - We describe two sisters aged 2 and 7 years, with monilethrix. The older sister was clinically less severely affected but, microscopically, the features of weathering and alternating nodes and internodes were more obvious. The younger girl had more severe alopecia, with shorter hair, but the microscopic features were less marked. Scanning-electron microscopy demonstrated only slight cuticular weathering in both cases, and evidence of breakage in the cuticle at points of no obvious cuticular pathology. Transmission-electron microscopy showed normal cuticle cells in cross-section, but an abnormal cortex. The abnormalities included areas of homogeneous non-fibrillar material, and a deviated axis of some microfibrils. We consider that these findings support the possibility that a cortical defect contributes significantly to the fragility of hair in monilethrix. This might explain why hair with marked beading can be stronger than hair from an affected sibling with less apparent abnormality. PMID- 8471519 TI - Bullous eruption of systemic lupus erythematosus: a clinicopathological study of four cases. AB - We describe the clinical, histological and immunopathological features of four female patients with the bullous eruption of systemic lupus erythematosus (bullous SLE). Three patients had circulating anti-basement membrane zone (BMZ) antibodies, and Western blot analysis in two cases revealed binding to type VII collagen. Immunoelectron microscopy in one of these patients demonstrated deposition of antibody in the lamina densa and sublamina densa regions, thus sharing immunopathological features with epidermolysis bullosa acquisita (EBA). The vesiculobullous lesions developed 8 months to 6 years after the initial symptoms of SLE, and cleared promptly with dapsone treatment. PMID- 8471520 TI - Cutaneous lymphadenoma: a case report and review of the literature. AB - We report a case of cutaneous lymphadenoma, a tumour first described by Santa Cruz and Barr under the name of 'lymphoepithelial tumour'. Twenty-three cases have been reported to date. The commonest site is the head and neck, and it is most commonly diagnosed in the fourth and fifth decades. The usual clinical diagnosis is basal cell carcinoma. To date, no recurrences have been observed after local excision. The tumour is composed of dermal lobules with a biphasic pattern of epithelial and lymphoid cells. It has been suggested that it arises as a result of faulty interaction between lymphocytes and epithelial cells. PMID- 8471521 TI - Acral epidermolytic hyperkeratosis. AB - We present a family with a distinctive pattern of epidermolytic hyperkeratosis which is mild, restricted to the distal parts of the limbs, and non-disabling. Features of the other variants of epidermolytic hyperkeratosis are discussed. PMID- 8471522 TI - Lamellar ichthyosis with laminated membrane structures. PMID- 8471523 TI - Successful treatment of sporotrichosis with oral fluconazole: a report of three cases. AB - We report three cases of sporotrichosis successfully treated with oral fluconazole. A verrucous lesion on the toe was cured after 126 days, and a lesion on the left foot resolved after 91 days' treatment. A case of lymphangitic-type sporotrichosis required 174 days of treatment to achieve a cure, and a higher dose (400 mg daily) was necessary in this case. Any side-effects were insignificant. We conclude that this new bis-triazole compound can be successfully used as an alternative treatment for sporotrichosis when conventional drugs must be avoided. PMID- 8471524 TI - Toxic epidermal necrolysis and systemic corticosteroids. PMID- 8471525 TI - New head louse repellent. PMID- 8471526 TI - Herpes simplex virus infection associated with bullous pemphigoid. PMID- 8471527 TI - Vitamin D analogues, marrow fibrosis and psoriasis. PMID- 8471528 TI - Cutaneous vasculitis in a patient infected with hepatitis C virus. Detection of hepatitis C virus RNA in the skin by polymerase chain reaction. PMID- 8471529 TI - The effect of platelet inhibitory therapy on prosthetic graft maturation. AB - Thirty-eight dogs were randomized to the thromboxane synthetase inhibitor CGS12790 (3 mg/kg), aspirin 150 mg and dipyridamole 50 mg (ASA + DPM) or placebo (PLA), all twice daily. Two days later, animals underwent bilateral superficial femoral artery replacement with knitted Dacron. Grafts were removed at two months and subjected to macroscopic and histological examination. Thirty dogs survived to two months. Percentage thrombus free area (TFA) was increased from 15.1 +/- 2.2 with PLA to 46.6 +/- 5.2 with CGS12970 (P < 0.001) and to 32.9 +/- 5.0 with ASA + DPM (P < 0.01). At the anastomoses, only CGS12970 significantly reduced neointimal thickness, promoted pannus ingrowth and improved endothelialization. Percentage luminal occlusion at the midgraft was reduced from 48.2 +/- 5.9 with PLA to 33.9 +/- 2.7 with CGS12970 (P < 0.05). These results provide further evidence that platelet inhibitory therapy reduces thrombosis but also that the platelet is involved in anastomotic maturation. Therapy directed against thromboxane synthesis has potential that may be useful in clinical practice. PMID- 8471530 TI - Production of salivary microlithiasis in cats by parasympathectomy: light and electron microscopy. AB - Salivary glands of cat were examined from 1 to 42 days following parasympathectomy and compared with contralateral normal control glands. Microliths were detected by light microscopy in none of 11 parotid, 31 out of 41 submandibular and four out of 22 sublingual glands following parasympathectomy, and one out of 19 parotid, five out of 28 submandibular and four out of 15 sublingual normal control glands. The greatly increased occurrence of microliths in the submandibular gland was statistically significant. Microliths in the parasympathectomized submandibular glands were detected by light microscopy most often in ductal lumina, followed by acinar lumina, ductal parenchyma, interstitial stroma, and acinar parenchyma. They were detected by electron microscopy also in the basement membrane overlying protruding processes of myoepithelial cells and in intraparenchymal macrophages. Intracellular microliths were in phagosomes. In the parasympathectomized submandibular glands, parenchymal atrophy was seen and particularly involved the striated ducts; secretory material and cellular debris were seen in lumina; and macrophages and neutrophils were more apparent than normally. The great increase of microlithiasis in the submandibular gland appears to be the result of secretory inactivity, and microliths appear to form in stagnant secretory material and cellular debris in lumina and in phagosomes of parenchymal cells. PMID- 8471531 TI - Comparison of surface fibroblastic cells in subcutaneous air pouch and synovial lining: differences in uridine diphosphoglucose dehydrogenase activity. AB - In contrast to synovial tissue, rat subcutaneous air pouch lining was found to lack cells showing high activity of uridine diphosphoglucose dehydrogenase, an enzyme involved in hyaluronan synthesis. This indicates that the properties of cells on the surface of synovium are not determined simply by tissue cavitation. Shearing forces may be more important in inducing the specialized behaviour of synovial surface fibroblasts. PMID- 8471532 TI - The effect of ischaemia on xanthine oxidase activity in rat intestine and liver. AB - Effects of 60 and 120 minutes of in-vitro ischaemia on the localization of xanthine oxidase activity were studied in rat intestine and liver. A histochemical method was applied on unfixed cryostat sections using a semipermeable membrane. The incubation medium contained hypoxanthine as substrate, cerium ions which capture the enzyme product, hydrogen peroxide, and sodium azide to inhibit catalase and peroxidase activities. In a second step reaction diaminobenzidine was polymerized in the presence of cobalt ions and hydrogen peroxide by decomposition of cerium perhydroxide. Large amounts of final reaction product were found in the cytoplasm of enterocytes and goblet cells of control small intestine. When the incubation was performed in the absence of substrate or in the presence of substrate and allopurinol, a specific inhibitor of xanthine oxidase activity, no reaction product was found. After 60 and 120 minutes of storage of tissue blocks at 37 degrees C enzyme activity was significantly reduced in the apical region of epithelial cells, whereas a high activity was present in the basal region of these cells. A very low xanthine oxidase activity was found in rat liver. Highest activity was present in endothelial cells, whereas in liver parenchymal cells, a more pronounced activity was found in pericentral than in periportal hepatocytes. Ischaemia up to 120 minutes did not affect the enzyme activity in livers. It was concluded that increased xanthine oxidase activity during ischaemia may not be responsible for cell damage during reperfusion in contrast with assumptions in the literature. PMID- 8471533 TI - Uridine diphosphoglucose dehydrogenase activity in normal and rheumatoid synovium: the description of a specialized synovial lining cell. AB - Although synovial lining cells (SLC) have been implicated in the production of hyaluronan (HA), which is found at particularly high concentrations in synovial fluid, the degree to which individual cells within the synovium are adapted to this particular function remains to be elucidated. Uridine diphosphoglucose dehydrogenase (UDPGD) activity is the irreversible, rate-limiting step in the production of UDP-glucuronate, an essential monosaccharide in the synthesis of HA. We have assessed the UDPGD activity, microdensitometrically, in individual lining cells of normal and rheumatoid (RA) synovium, using a modified quantitative cytochemical method. In normal synovium, high activity was confined to the cells of the lining with negligible activity in the deeper subintima. The mean UDPGD activity/cell in lining cells of rheumatoid synovium was significantly lower than the activity in normal SLC. In some samples of RA and normal synovium, a bimodal distribution of cells was evident in the lining on the basis of UDPGD activity, a zone of cells in the basal layers with high UDPGD activity and a separate population of cells in more superficial layers with relatively low UDPGD activity. The results suggest that a particular population of cells is present, consistently in normal and more variably in RA synovial lining, which have high UDPGD activity/cell and may be involved in the production of HA. Furthermore, in RA synovium both the UDPGD activity/cell and the relative proportion of these cells within the lining appear to be decreased. PMID- 8471534 TI - Ultrastructural changes in rat adipomusculocutaneous flaps during warm ischaemic storage and reperfusion. AB - Electron microscopy (EM) was used to evaluate ultrastructural changes in adipomusculocutaneous rat flaps which had been stored for 0, 2, 4, 6 and 8 hours under normothermic conditions (37 degrees C). The effects of treatment with desferrioxamine (DFX) or hypertonic citrate flush (HCA), prior to 4 hours of storage, were compared to untreated flaps which had been stored for 4 hours. Ultrastructural changes caused by 30 minutes of reperfusion, were also studied. Most ultrastructural alterations occurred between 2 and 4 hours of warm storage and there were further changes in some cells after short periods of reperfusion. DFX decreased smooth muscle damage and HCA protected adipocytes but neither of these agents preserved endothelial cells. These studies indicated that free radical-dependent and independent mechanisms were both involved in events which led to flap necrosis after periods of warm storage and reperfusion. PMID- 8471535 TI - The effect of cyclosporin A on rabbit nephrotoxic glomerulonephritis. AB - The effect of cyclosporin A on the development of the autologous phase of experimental rabbit glomerulonephritis was assessed. The glomerulonephritis was induced by a single intravenous injection of duck anti-rabbit glomerular basement membrane globulin (molecular weight: 115 kDa) into adult rabbits. After 5-7 days, diffuse proliferative glomerulonephritis with proteinuria was observed in all the animals not treated with cyclosporin A (control group). The cyclosporin A treatment was started simultaneously with the injection of duck globulin. This attenuated the glomerular lesion, resulting in a normal urinary protein excretion. The serum level of autologous anti-duck IgG was reduced. In the group of rabbits which received an injection of duck anti-rabbit glomerular basement membrane globulin, cyclosporin A treatment and an additional high dose rabbit anti-duck globulin 8 days later again no glomerulonephritis was observed. However, cyclosporin A treatment had no effect on the observed duck immunoglobulin-induced passive Arthus phenomenon. PMID- 8471536 TI - Can changes in microcirculation explain capillary growth in skeletal muscle? AB - Capillary growth (increase in capillary/fibre (C/F) ratio by 20%) was elicited in skeletal muscles either by long-term increase in blood flow (5 weeks administration of prazosin in drinking water, 50 mg/l) or 7 days electrical stimulation (8 h/day at 10 Hz). Mechanisms that could explain it ((a) increased interaction of blood components with endothelial cells (due to increased haematocrit or decreased intermittency of flow); (b) increased velocity of flow and thus shear stress; (c) increased capillary diameters and thus wall tension) were studied in vivo. Red blood cell velocity (Vrbc), vessel diameters and intermittency of capillary flow were measured in superficially located capillaries in rat tibialis anterior muscles about 18 hours after the last treatment, in prazosin treated and chronically stimulated animals, and also in animals where red blood cell interaction with capillary endothelium was increased by elevating haematocrit from 43.2 +/- 1.7% to 60.9 +/- 0.72% by 11 weeks administration of CoCl2. Animals of comparable size and sex were used as controls. Capillaries in chronically stimulated muscles had increased Vrbc at rest (0.42 +/- 0.06 mm/s vs 0.27 +/- 0.04 in control muscles) and somewhat wider diameters, although the intermittency of flow was not different from control muscles. Capillaries in prazosin treated rats had a lower intermittency of flow, similar diameters and considerably higher Vrbc (0.53 +/- 0.06 mm/s) than control animals. CoCl2 treatment resulted in a similar intermittency of flow, did not alter capillary diameters or Vrbc and did not result in an increase in C/F ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471537 TI - Progressive splenomegaly with increasing extramedullary haematopoiesis in subcutaneous 9L-glioma bearing rats. AB - We have succeeded in inducing progressive splenomegaly by inoculating 9L-glioma cells into the back subcutaneous regions of Fischer rats. The progressive splenomegaly was histologically characterized by progressively increased extramedullary haematopoiesis. Immunohistochemically Leu 7 positive cells were present in the enlarged spleen, suggesting that the spleen possessed natural killer (NK) cells. However, the splenic NK cell activity obtained in a 4h-51Cr release assay at 5 weeks after inoculation was below 5%, suggesting that the cytotoxic function of the NK cells was depressed. Bone marrow morphologically appeared not to be suppressed. Although the exact cause and mechanism of the progressive splenomegaly with prominent extramedullary haematopoiesis and severe suppression of the splenic NK cell activity remains speculative at present, it could be a unique manifestation of a systemic host-reaction reflected by the 9L glioma continuously growing in the subcutaneous regions. This experiment could be a useful approach to the study of splenic and other reticuloendothelial roles in host-immunity in the tumour bearing state. PMID- 8471538 TI - Growth factor expression during rat development: a comparison of TGF-beta 3, TGF alpha, bFGF, PDGF and PDGF-R. AB - At least part of the mechanism underlying fetal development appears to be the production of a number of growth factors considered important in the process of tumour formation. Using immunocytochemistry, we have investigated the temporal and spatial pattern of expression of some of the important growth factors, by the fetus. We describe here the cellular localization of transforming growth factor beta 3 (TGF-beta 3), platelet derived growth factor (PDGF) and its receptor (PDGF R), TGF-alpha and basic fibroblast growth factor (bFGF) in the fetal rat from day 13 to 21 of gestation. Using antisera raised against an N-terminal portion of TGF beta 3, immunoreactivity peaked around day 16 and was seen predominantly within epithelial cells. However, using antisera raised against the C-terminal of this molecule immunoreactivity was seen exclusively within the extracellular matrix underlying adjacent epithelia, and was maintained up until day 21 of gestation. Strong expression of TGF-alpha was seen in cells of most organs throughout the gestation period studied. Immunoreactivity for bFGF, PDGF and PDGF-R peaked around day 18 in both epithelial and mesenchymal cells of all major organ systems and then declined by day 21. These data suggest distinct roles for each factor during embryogenesis and tumorigenesis. PMID- 8471539 TI - Anti-glomerular basement membrane glomerulonephritis (anti-GBM GN) in the mouse: BrdU-labelling indices and histological damage. AB - In-vivo BrdU incorporation and visualization by immunohistochemistry, previously reported in normal mouse kidney, were applied to a mouse model of anti-GBM GN, induced by immunization with rabbit anti-mouse GBM antiserum, to assess the contribution of capsular cell proliferation in the development of crescents. A significant increase (P = 0.003) in the BrdU-labelling index (LI) for capsular cells was observed, as compared to normal mice (5.76 +/- 1.1 vs 0.70% +/- 0.12%). Elevated LI were also observed for tuft and tubular cells but these increases were not statistically significant. It was concluded that, in this model, capsular cell proliferation is a major contributory factor to the formation of cellular crescents. In addition, other pathological features, indicative of glomerular damage, were assessed semi-quantitatively alongside numbers of labelled capsular cells per glomerulus. It was found that podocyte vacuolation is strongly associated with, and may precede, proliferation, suggesting some common causative factor. Fibrin, when present, was confined within the tuft capillary loops and was only weakly associated with either podocyte vacuolation or capsular cell proliferation. It was concluded that this protein does not play a major role in the initiation of pathological damage. Finally, glomerular lesions were found to be randomly distributed. Thus, the idea of intraglomerular signalling, resulting in 'clustering' of damaged glomeruli, is not supported. PMID- 8471540 TI - Factors influencing the ability of different mycoplasmas to colonize the genital tract of hormone-treated female mice. AB - Colonization of the genital tract of female mice, mainly BALB/c, by Mycoplasma genitalium, M. pneumoniae and M. pulmonis was enhanced by pretreatment of the mice with progesterone. M. fermentans, M. hominis and M. salivarium, and three serotypes and two untyped strains of Ureaplasma urealyticum colonized under the influence of oestradiol but not progesterone. Mycoplasmas dependent on progesterone were glucose-metabolizing, with strong haemadsorptive and other attachment properties, and possessed a terminal structure. Mycoplasmas dependent on oestradiol were arginine or arginine/glucose metabolizing. Ureaplasmas also required oestradiol. The oestradiol-requiring group appeared to be less cytadsorptive and devoid of a morphological terminal structure. Mycoplasmas that had had multiple passes in media were less able to colonize. This may be one, but not the only, reason for the failure of seven mycoplasmas to colonize under the influence of either hormone. The observations suggest the existence of a receptor mechanism for colonization, progesterone-requiring mycoplasmas being exposed to, and needing, genital tract cells different from those exposed to oestradiol requiring mycoplasmas. PMID- 8471541 TI - Determination of dihydrocodeine in hair of opiate addicts by GC/MS. AB - After the examination of more than 300 hair samples of suspected heroin abusers, a large number of which proved positive, we can say that high concentrations of dihydrocodeine can be determined either in addition to, or in the place of, morphine and also frequently in combination with codeine. The opiates were extracted after dissolving the hair samples in NaOH and hydrolysis with HCl. The quantitative determination of dihydrocodeine was achieved by derivatisation with HFBA using GC/MS at m/u = 497. Dihydrocodeine is used in antitussive drugs. After the examination of individual hair samples, it was obvious that some heroin consumers had switched to dihydrocodeine. This may lead to the conclusion that dihydrocodeine itself is used either as an intoxicating drug or to reduce withdrawal symptoms. The increasing number of positive samples should be noted by the legal authorities. PMID- 8471542 TI - Population genetics of three VNTR polymorphisms in two different Spanish populations. AB - Two different Spanish populations, one from Galicia (NW Spain) and the other from the rest of Spain, have been analyzed at three different hypervariable loci (YNH24, MS43a and MS31) using the EDNAP electrophoretic protocol and HinfI as restriction enzyme. Although the "rest of Spain" population is a clearly stratified population using classical blood groups, no evidence of stratification for these loci has been found and the differences to the Galician population were not significant, which suggests that a common Spanish population data-base could be possible. A semiparametric model is proposed for estimating frequencies, using the smoothed cross-validation of Hall et al. (1992) to calculate the size of the window utilized. PMID- 8471543 TI - PCR-amplification and detection of the human D1S80 VNTR locus. Amplification conditions, population genetics and application in forensic analysis. AB - A series of experiments has been performed to evaluate amplification and typing of the D1S80 VNTR locus. The validation study that has been carried out showed that correct D1S80 typing results can be obtained when a defined amplification protocol and a high-resolution polyacrylamide gel electrophoresis method are used. The use of the Chelex extraction protocol has substantially reduced the processing time. DNA-extraction, amplification and subsequent typing can be performed in one day. The discrimination power of this locus is 0.94 in a Dutch Caucasian population sample. The system is extremely sensitive: 0.1 ng of genomic DNA gave a correct typing result. The test could also detect the correct genotypes in mixed samples containing DNA from different individuals. Even if the major type was in a 20-fold excess, the minority type could still be amplified and typed correctly. We have found no deviation from Hardy-Weinberg equilibrium in a Dutch Caucasian population sample. Evidence for the somatic stability of this locus was obtained from a set of experiments where we compared DNA-profiles from corresponding blood, semen and saliva samples. The results of this study suggest that in the near future analysis of the D1S80 locus by DNA-amplification can be applied in actual forensic case work. PMID- 8471544 TI - Genetic variation of microsatellite markers D1S117, D6S89, D11S35, APOC2, and D21S168 in the Spanish population. AB - We have used PCR amplification to analyse the allele frequency, distribution and heterozygosity of 5 microsatellite markers (D1S117, D6S89, D11S35, APOC2, and D21S168), in a sample of 100 unrelated Spanish individuals. The loci tested exhibit wide allelic variability having 7-17 alleles, PIC (polymorphic information content) between 0.79 and 0.86, and heterozygosity between 0.81 and 0.86. D1S117 and D21S168 have unimodal distribution, APOC2 has 4 common alleles which account for 71% of the total variation, D11S35 has a bimodal distribution and D6S89 is trimodal. The allelic distribution observed for each locus is in agreement with slippage and mispairing as the main mechanisms involved in the evolution of microsatellite alleles. Multiplex amplification of loci D6S89 and APOC2 was possible due to their non-overlapping allele sizes. The rapidity with which microsatellites can be analysed, and the accurate determination of alleles, make these markers very powerful tools for genetic typing. The information obtained for loci D1S117, D6S89, D11S35, APOC2, and D21S168, provides a basis for their use for DNA typing and paternity analysis in the Spanish population. PMID- 8471545 TI - Abuse of codeine separated from over-the-counter drugs containing acetylsalicylic acid and codeine. AB - In Denmark a new trend concerning the abuse of codeine has been observed. Danish drug abusers have discovered that codeine is easily separated from certain drugs containing acetylsalicylic acid and codeine. When separated the codeine can be used either orally or intravenously. Three different drugs combining acetylsalicylic acid and codeine are available in Denmark, but codeine is only easily separable from one of these. Applying the same procedure to the two other drugs produces unpredictable or unfavourable ratios of codeine to acetylsalicylic acid. In several countries, however, similar drugs combining acetylsalicylic acid and codeine are available. It is not possible from a list of constituents to predict how easily codeine can be separated from a particular drug. Therefore it is strongly recommended that relevant drugs are tested at local forensic laboratories. In case codeine is found to be very easily separated from a product appropriate action should be taken. PMID- 8471546 TI - Pharmacological studies on meprobamate incorporation in human beard hair. AB - The time course of appearance of meprobamate in beard hair after single oral administration (400, 800, or 1200 mg) was monitored in 3 groups of 4 subjects by GC/MS. Meprobamate appeared in beard hair approximately 4-5 days after administration and peaked during the 7-9th day. Drug levels in beard hair appeared to be dose-related. PMID- 8471547 TI - Postmortem estimation of age at death based on aspartic acid racemization in dentin: its applicability for root dentin. AB - The extent of aspartic acid racemization in total dentin and in dentin protein fractions from the roots of third molars was determined. In several cases coronal dentin was also investigated. The results of other authors, according to which the racemization of aspartic acid in root dentin apparently proceeds differently than in coronal dentin, could be confirmed. Consequently, the data published so far on age determination based on the extent of aspartic acid racemization in coronal dentin and the "entire dentin of longitudinal sections" cannot be applied to root dentin. In total root dentin and the acid soluble protein of root dentin, a close relationship was observed between the extent of aspartic acid racemization and age. Accordingly, estimation of age at death based on aspartic acid racemization in dentin is also possible for root dentin, apparently with good results. This is important particularly in those cases where a large portion of the coronal dentin is absent, for instance following dental treatment. In the investigation of root dentin, regression equations specific for root dentin must be employed in the estimation of age at death. Corresponding equations for third molars were calculated. PMID- 8471548 TI - Experience with the PCR-based HLA-DQ alpha DNA typing system in routine forensic casework. AB - The results of HLA-DQ alpha typing from 42 routine forensic cases using the polymerase chain reaction (PCR) were analyzed regarding the reliability, discrimination efficiency and informative value of this system in a given case. The cases included stain typing from a variety of different substates, i.e. blood and semen stains, mixed body fluids, single hairs, cigarette butts, material from fingernail scratches, as well as identification and paternity cases on postmortem and fixed tissue. A total of 125 individual stain and tissue samples were included. PCR amplification was achieved in 70% of these samples. In cases with mixed body fluids, e.g. sperm and vaginal cells from rape cases, DQ alpha typing was always carried out successfully. However, only approx. 42% of all samples that could be typed were relevant regarding the inclusion or exclusion of a suspect. This was mostly due to the limited number of alleles that can be typed at the HLA-DQ alpha locus or to the fact that the stain or hair samples did not originate from the perpetrator, but from the victim or from other persons not related to the crime. PMID- 8471549 TI - Interferon alpha-recombinant in the treatment of follicular lymphoma patients. PMID- 8471550 TI - A role for proliferative measurements in clinical oncology? AB - I feel a simple but properly determined proliferative measurement is within our grasp for clinical use. In addition, multi-parametric flow cytometry offers a means of obtaining more detailed cell kinetic information, using DNA staining combined with staining with one or more antibodies directed against either BrdUrd or proliferation-related proteins. PMID- 8471551 TI - The pharmacological management of cancer pain. Part 1: The role of non opioid and adjuvant drugs. PMID- 8471552 TI - Routine follow-up of patients after primary therapy for early breast cancer: changing concepts and challenges for the future. AB - In an era of increasing financial constraints, physicians are being forced to critically re-evaluate various clinical practices that have not been shown to be cost-effective or associated with definitive patient benefit. Routine follow-up programs following primary therapy for early-stage breast cancer vary widely from centre to centre, and although the subject of numerous retrospective analyses, they have not been prospectively evaluated to date. This review paper presents arguments for changing the emphasis of follow-up visits and stresses the need for prospective clinical and cost-benefit evaluations of current follow-up practices. PMID- 8471553 TI - Prognostic significance of proliferative activity and ploidy in node-negative breast cancers. AB - BACKGROUND: Cell kinetics and DNA ploidy have provided relevant information on the natural history of breast cancer. We assessed the prognostic role of proliferative activity and ploidy, alone and in association with tumor size, estrogen (ER) and progesterone (PgR) receptors. PATIENTS AND METHODS: In a series of 340 women with resectable node-negative breast cancers given local-regional therapy alone until relapse, proliferative activity was determined as the 3H thymidine labeling index (3H-dT LI) and flow-cytometric S-phase cell fraction (FCM-S), as quantified by using different modeling systems. DNA ploidy, ER and PgR content were determined on frozen samples by FCM and by the dextran-coated charcoal absorption technique, respectively. RESULTS: FCM-S estimates obtained by the different models were weakly associated with one another and to the corresponding 3H-dT LIs. Four-year relapse-free survival was significantly predicted by 3H-dT LI, ploidy and tumor size but not by FCM-S. Multiple regression analysis showed that 3H-dT LI, ploidy and tumor size retained their prognostic significance and that 3H-dT LI was the most significant indicator of relapse (p = 0.009). CONCLUSIONS: The finding that 3H-dT LI and ploidy are weakly related and provide independent prognostic information could allow a more accurate identification of patients at different risk of relapse. PMID- 8471554 TI - Dose intensification of cisplatin chemotherapy through biweekly administration. AB - PURPOSE: Dose intensity (DI, expressed in mg/m2/wk) may be an important factor in the clinical use of cisplatin (DDP). We have explored the shortening of the cycle interval as a way to increase the DI of DDP. PATIENTS AND METHODS: DDP 180 mg/m2 was given intravenously (i.v.) over 4 hours; sodium thiosulfate (STS) was given i.v. in the opposite arm at a loading dose of 4 g/m2, followed by 12 g/m2 over 6 hours. Each cycle was repeated every two weeks. Seventy-five cycles were administered to 28 patients in this clinical trial. RESULTS: In 19 patients who received 2 or more cycles of chemotherapy, a delay of three or more days was required on 17/66 courses (26%); the mean DDP DI actually received by these patients was 83 mg/m2/wk (88% of the planned DI). The major side effect was ototoxicity; this occurred in 9 patients (33%), but none required a hearing aid. Myelosuppression was moderate with thrombocytopenia greater than neutropenia. Nephrotoxicity (creatinine > 2 mg/dl) occurred on only 2 cycles (3%). Three patients (11%) developed symptoms of peripheral neuropathy. In 23 evaluable patients, the overall response rate was 39%. CONCLUSION: It is feasible to give 180 mg/m2 of DDP and STS every two weeks with tolerable nephrotoxicity but without blocking other types of toxicity, such as myelosuppression and ototoxicity. The shortening of cycle intervals resulted in a markedly increased DI. PMID- 8471555 TI - Biochemical modulation of 5-fluorouracil: a randomized comparison of sequential methotrexate, 5-fluorouracil and leucovorin versus sequential 5-fluorouracil and leucovorin in patients with advanced symptomatic colorectal cancer. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group. AB - BACKGROUND: The optimal chemotherapy for advanced colorectal carcinoma is not known. Two regimens, both based upon biochemical modulation of 5-FU, were compared in a randomized multicenter trial. PATIENTS AND METHODS: A total of 202 symptomatic patients were randomly allocated to receive either sequential methotrexate, 250 mg/m2, during the first 2 hours and 5-FU, 500 mg/m2, at hours 3 and 23 followed by leucovorin rescue initiated at hour 24 (15 mg x 8) (MFL) or sequential 5-FU 500 mg/m2 followed by leucovorin 60 mg/m2 30-40 minutes later, on days 1 and 2 (FLv). Treatments were repeated every 14 days for eight courses and then every 3 to 4 weeks. Four patients were unevaluable. RESULTS: The two treatments were equally effective with respect to objective response rates (complete (CR)+partial (PR), MFL 17%, FLv 21%), subjective response rates (symptom relief in the absence of severe adverse effects, 45% vs. 37%), and survival (median 7.5 vs. 9 months). All responses lasted at least 4 months. Overall, toxicity was low and comparable between the groups, but serious toxicity was more common in the MFL group. CONCLUSIONS: Since FLv is easier to administer and carries less risk for serious toxicity, it should be recommended as a first line treatment before MFL. On either regimen, about 40% of symptomatic patients can expect palliation, i.e., symptomatic relief without severe adverse effects, for at least 4 months. PMID- 8471556 TI - Carboplatin and 5-fluorouracil in poor performance status patients with advanced urothelial cancer. AB - BACKGROUND: In view of the difficulties in administering aggressive treatment to elderly patients, frequently with concomitant medical problems, a treatment program with the combination of carboplatin and 5-FU for advanced urothelial tumors was designed. The aim was to maintain an efficacious therapeutic schedule while minimizing toxicity. PATIENTS AND METHODS: Twenty-three patients with advanced bidimensionally measurable urothelial carcinoma were given carboplatin 100 mg/m2 and 5-fluorouracil 500 mg/m2 days 1-3 which was escalated to carboplatin 125 mg/m2 and 5-fluorouracil 625 mg/m2. 5 patients were > 70 years, the ECOG performance status was 2-3 in 10 patients (43%), and the creatinine was > 2.0 mg/dl in 3 patients (13%). Five patients (22%) had pre-existing cardiac disease, and 1 had hepatopathy. Nine patients (39%) had prior cisplatin. RESULTS: Ten patients remained at level 1, and 12 others had the dosage escalated to level 2. Twenty-one patients are evaluable for response. Response was observed in 5 of 21 (24%) evaluable patients (95% confidence limits 15%-33%), only at dose level 2. There was 1 CR (5%) and 4 PR (19%). There were no responses in patients who had prior DDP versus 5 of 13 (38%) responses in patients who had not had prior DDP. The median time to response was 2 months. The median duration of response was 8 months. At level 2 myelotoxicity was significant, and led to a return to level 1 in 2 patients. Nine of 12 patients (75%) treated at level 2 had grade 3 leukopenia, and 1 patient had nadir sepsis. 4 patients (33%) had grade 4 thrombocytopenia. CONCLUSIONS: Moderate activity was shown with this regimen in untreated patients at level 2. This regimen presents a feasible outpatient alternative for patients who are unable to undergo more aggressive chemotherapy. PMID- 8471557 TI - Malignant lymphoproliferative disorders in liver cirrhosis. AB - BACKGROUND: Lymphoproliferative disorders in patients with liver cirrhosis, although uncommon, have been reported in at least 49 cases. Some authors have suggested that the association between chronic liver disease and lymphoma is not coincidental, that immune mechanisms may be pathogenetically involved. PATIENTS AND METHODS: In the present study we calculated the incidence rate of lymphoproliferative disorders in 334 liver cirrhosis patients (201 males, mean age 59 +/- 12; 133 females, mean age 61 +/- 11) treated at the Gastroenterology Department of the Mauriziano Hospital in Turin from January 1987 to September 1990. RESULTS: We diagnosed 12 lymphoproliferative disorders, corresponding to an incidence of 9.56/1,000 person-years, a figure much higher than expected on the basis of the incidence rate registered in the Turin general population. Six of the 12 lymphoproliferative disorders were non-Hodgkin's lymphomas of the stomach, a proportion by far exceeding expectation. CONCLUSIONS: Our data support the hypothesis that the association between chronic liver disease and lymphoproliferative disorders is not just coincidental, and suggest that liver cirrhosis might be considered an immunological disturbance which entails an increased risk of developing lymphoproliferative disorders. Mechanisms causing lymphoproliferative disorders to develop in the course of chronic liver disease have been hypothesized. PMID- 8471558 TI - Effective salvage chemotherapy in relapsed or refractory non-Hodgkin's lymphoma. AB - BACKGROUND: Over the last few years, high-dose chemotherapy has been extensively investigated in relapsing/refractory non-Hodgkin's lymphoma (NHL). However, this approach is reserved to a limited subset of cases and new conventional-dose second-line chemotherapies need to be investigated. PATIENTS AND METHODS: Thirty consecutive out-patients with refractory or recurrent NHL were given polychemotherapy in a regimen consisting of ifosfamide, mitoxantrone and etoposide on day 1 and vindesine, cisplatinum and cytosine arabinoside on day 15: courses were repeated every 29 days. Five patients had refractory disease following first-line chemotherapy and 25 were relapsing. RESULTS: The median number of administered cycles was 4 (range 2-8). We observed 16 complete (53%; 95% confidence interval, 34%-72%) and 3 partial remissions, for an overall remission rate of 63% (95% confidence interval, 44%-80%). Responses were seen only among patients who achieved at least a partial response during first-line therapy. The median duration of complete remission was 15 months (range 5-47+), whereas median survival of the treated patients was 26 months (range 2-50+). Five patients were long-term responders after 34+, 35+, 46+, 46+ and 47+ months. No life threatening toxicity was observed. The main side effects were myelosuppression, nausea/vomiting and alopecia. CONCLUSIONS: The proposed regimen is feasible and effective in terms of complete remission rate and disease-free survival, suggesting that this treatment may be potentially curative in a subgroup of relapsed patients with limited tumor burden and normal LDH values. A more aggressive approach is needed in refractory patients. PMID- 8471559 TI - A phase II study of weekly edatrexate (10-EDAM) in metastatic melanoma. A National Cancer Institute of Canada Clinical Trials Group study. AB - BACKGROUND: Phase I and II clinical trials have demonstrated acceptable toxicity and promising activity of Edatrexate (10-EDAM). The objective of this multicentre phase II study was to determine the efficacy and toxicity of this agent in patients with metastatic melanoma. PATIENTS AND METHODS: Sixteen previously untreated patients with metastatic melanoma received 10-EDAM, 80 mg/m2/week intravenously. Patients were evaluated for response and toxicity. RESULTS: There were no objective responses. The median dose intensity of 10-EDAM actually delivered was 56.25 mg/m2/week (70% of projected). Mucositis of any degree was encountered in 93.8% of patients. Grade 3 or 4 mucositis, skin rash, nausea, abdominal pain, neutropenia, thrombocytopenia, anemia and hyperbilirubinemia each were encountered in 1-2 patients. There was 1 toxic death due to 10-EDAM. CONCLUSION: 10-EDAM is an inactive agent in metastatic melanoma. PMID- 8471560 TI - Gastric adenocarcinoma after gastric lymphoma: the role of chemoradiotherapy. PMID- 8471561 TI - Should we regard CA125 as the indication to treat relapsing ovarian cancer? PMID- 8471562 TI - Present-day performance qualities of cardiotocographs. AB - Legislation and standards applying to medical electrical equipment are reviewed. Although there are no official standards for cardiotocographs, de facto standards can be defined. The paper introduces the present-day performance qualities of cardiotocographs and the factors which affect the quality of the data. The measures used to evaluate the ability of cardiotocographs to indicate correctly the fetal heart rate and maternal uterine activity are discussed. Present-day cardiotocographs generally perform well but the physiological variables need to be defined in order to produce equipment in keeping with clinical needs. PMID- 8471563 TI - The fetal ECG: accuracy of measurements. AB - Analysis of fetal heart rate is very dependent upon the accuracy with which fetal events can be timed. This depends upon signal quality and the type of processing used in signal analysis. Signal quality is affected by mode of recording and positioning of sensors. Signal loss can be kept to below 5% in routine clinical practice with appropriate attention to technique. Accuracy of beat-to-beat measurement needs to be 1 ms if short-term variability (epoch length 1/16 min) is to be assessed reliably. PMID- 8471564 TI - Doppler ultrasound monitoring technology. AB - Developments in the signal processing of Doppler ultrasound used for the detection of fetal heart rate (FHR) have improved the operation of cardiotocographs. These developments are reviewed and the advantages and disadvantages of the various Doppler and signal processing methods are compared. PMID- 8471565 TI - Signal processing and display--cardiotocographs. AB - The technology used in cardiotocographs limits the basic resolution of the recorded data. The limitations and errors generated by the data collection, signal processing (autocorrelation) and printing the fetal heart rate (FHR) are discussed. Although adequate for displaying baseline variability, present-day cardiotocographs are incapable of displaying beat-to-beat changes in FHR. PMID- 8471566 TI - Communicating the significance of the fetal heart rate record to the user. AB - Fetal heart rate (FHR) records should be presented as measurements derived from numerical analysis. Such analysis requires computerized systems. The Oxford system is the longest established and most tested of the systems available. It could provide the basis for a standardized approach to the numerical analysis of antepartum FHR records. Intrapartum FHR monitoring is of uncertain clinical value. It is premature to recommend standards for numerical analysis to upgrade the present methods of data presentation during labour. Once the patterns of abnormality are better defined numerically such standards will be mandatory because intrapartum FHR records cannot be interpreted reliably by eye. PMID- 8471567 TI - Measurement of uterine activity in labour--clinical aspects. AB - Intra-uterine pressure measurement remains the most objective way of measuring uterine activity in labour, and in this respect is superior to clinical assessment or external tocography. However there is little evidence to show that improving the assessment of uterine activity in labour is associated with an improvement in the outcome of labour for mother or fetus. It seems logical that use of intra-uterine pressure monitoring will provide additional safety in women with a scarred uterus, breech presentation, high parity, or apparent failure of response to induction or augmentation of labour with the usual dose rates of oxytocics, but this has not been established by appropriately sized clinical trials. Further research to establish the role of uterine activity measurement in labour is urgently needed. PMID- 8471568 TI - Standards in fetal monitoring--practical requirements for uterine activity measurement and recording. AB - External monitoring of uterine contractility in human labour can record contraction frequency accurately, but cannot determine true intra-uterine pressure reliably. It is therefore suitable for use in spontaneous labour where there is a need for a marker of contractions to aid in continuous fetal heart rate pattern interpretation. Intra-uterine pressure measurement can provide quantitative information more reliably over intervals of 10-60 minutes. Although active pressure values for individual contractions can vary by up to 50% when measured simultaneously by two or more intra-uterine catheters/transducers, this variation is not systematic and cumulative measures vary by less than 5%. The measurement of baseline tone is affected by variables not related to uterine activity and should therefore be excluded when quantitative measures are made. PMID- 8471569 TI - Clinical overview of cardiotocography. AB - Twenty years after its widespread introduction, the role of continuous fetal heart rate and contraction monitoring in labour (cardiotocography, CTG) remains uncertain. Although a normal pattern is very reassuring about fetal condition, the predictive value of an abnormal pattern is low. In most studies the use of CTG has been associated with an increase in intervention in labour, particularly caesarean section, without clear evidence of benefit. Fetal blood sampling is the most useful associated technique for minimizing unnecessary intervention. The relationship between fetal heart rate, fetal blood pH changes and long-term outcome remains obscure and further work to clarify this relationship is urgently needed. PMID- 8471570 TI - Litigation and the cardiotocogram. AB - The extent of the liability in obstetric litigation is discussed. Arguments between experts reveal the lack of agreed standards in cardiotocography. This paper discusses the problems which need to be addressed when defining what constitutes an abnormal cardiotocogram (CTG), how long it needs to abnormal before it is significant, the contribution made by inadequate equipment and the question of whether it is defensible to decide positively not to monitor. Records need to be archived for a minimum of 25 years. PMID- 8471571 TI - Recovery from intravenous sedation with midazolam--the value of flumazenil. AB - A total of 40 patients receiving intravenous midazolam for surgical removal of impacted wisdom teeth were randomly assigned to recover either spontaneously or undergo reversal by the benzodiazepine antagonist flumazenil. Whilst initial postoperative recovery to a 'fully awake' state occurred more rapidly in the reversal group, objective psychomotor testing revealed significantly poorer performance postoperatively compared with spontaneously recovering patients; this emphasises the need to retain patients for at least 1 h prior to discharge home. PMID- 8471572 TI - Hemimandibular reconstruction with bipedicled scapular osteocutaneous free flap. AB - A case report is presented on the successful use of a bipedicled scapular osteocutaneous free flap in a young woman, whose hemimandible was resected because of sarcoma, 1 year prior to presentation. The postoperative course was uneventful and donor site morbidity minimal. PMID- 8471573 TI - Reconstruction of full-thickness cheek defects with a bipaddled radial forearm flap. AB - The use of a double folded radial forearm free flap for the reconstruction of full thickness cheek defects in six patients is reported. A brief comparison with other methods is made and a modification of the flap for the reconstruction of the angle of the mouth is presented. PMID- 8471574 TI - Parathyroid carcinoma presenting with a brown tumour of the mandible in a young man. AB - A 27-year-old man presented to his dentist with a swelling in his lower jaw. Histology revealed this to be a brown tumour associated with primary hyperparathyroidism and severe but asymptomatic hypercalcaemia. A large parathyroid adenoma was removed and the serum calcium fell to normal. Hypercalcaemia recurred and re-exploration of the neck revealed parathyroid metastases in cervical lymph nodes. A modified radical neck dissection was performed and he has remained normocalcaemic on Vitamin D analogues for 2 years. Bone disease of the mandible is a very rare presentation of primary hyperparathyroidism. The diagnosis of parathyroid malignancy is often difficult histologically, and the optimum treatment is uncertain. PMID- 8471575 TI - Lympho-epithelial cysts: a maxillofacial surgeon's perspective. AB - Cervical swellings are referred to Oral and Maxillofacial Surgeons and may subsequently be diagnosed as lympho-epithelial cysts. The clinical presentation of such swellings appears to differ from that seen in other specialties also treating these cysts in that a larger proportion of lympho-epithelial cysts presenting to our specialty are infected, which complicates the diagnosis and also the subsequent management. We present our recent experience of 5 patients who underwent excision of a lympho-epithelial cyst, all of which were infected on initial presentation and four of which were associated with concurrent ipsilateral dento-alveolar infection. The fifth case presented with rapid development of a cervical swelling in the immediate post-natal period. As these cysts contain abundant lymphoid tissue as an integral part of the lymph drainage system of the head and neck, we propose that the management of an infected lympho epithelial cyst should include a full clinical and radiographic examination of the oral cavity for a possible focus of infection and indeed any patient awaiting surgery for a non-infected cyst would benefit from an examination of the mouth and treatment of any sites of chronic infection. PMID- 8471576 TI - Bifid mandibular condyle resulting from a sagittal fracture of the condylar head. AB - Sagittal or vertical fractures of the mandibular condyle and chip fractures of the medial part of the condylar head are very rare entities and their identification is difficult with conventional radiographs. We report a case of a unilateral bifid mandibular condyle which resulted following a sagittal condylar fracture. This was associated with a chip fracture of the medial part of the condylar head on the contralateral side. These types of condylar fracture do not require any surgical treatment, but early mobilization is indicated. PMID- 8471577 TI - A simple technique to improve access to the adult palate. AB - A simple method to facilitate good access to the palate of the adult patient using the Dingman gag is described. PMID- 8471578 TI - Civilian attachments for Defence Services trainees. PMID- 8471579 TI - Retrobulbar haematoma. PMID- 8471580 TI - Retrobulbar haematoma. PMID- 8471581 TI - Retrobulbar haematoma. PMID- 8471582 TI - Living with the reforms. PMID- 8471583 TI - Primary closure of cleft palate: a functional approach. AB - The role of the different zones of palatal mucosa in maxillary growth are considered and their relevance in surgery of cleft palate discussed. A method of cleft palate repair is described, based on a functional repair of the soft palate, followed by later closure of the hard palate taking into account the anatomy and physiology of the palatal mucosa. PMID- 8471584 TI - A comparison of two classification systems for hemifacial microsomia. AB - The classification of hemifacial microsomia (HFM) aids in diagnosis, treatment planning, prognostic predictions and data evaluation. The aetiological and phenotypic heterogeneities of HFM, however, make its classification problematic. This study used data from 50 patients to examine the classification of HFM and to compare two systems: OMENS and SAT. The results were concordant with current literature and demonstrated the phenotypic heterogeneity of HFM. Essentially, both classifications embody the major craniofacial defects, but the OMENS system appears to be further refined by its differentiation between soft tissue and nerve defects, and between orbital and mandibular defects. Neither system, however, records deafness or grades auricular tags, although tags occurred in 34% of cases and two patients with otherwise 'normal' ears had tags. Therefore, it is suggested that auricular tags be graded as minor ear malformations. Furthermore, the OMENS system could be strengthened by the addition of an asterisk to the acronym in cases with serious non-craniofacial anomalies, for example OMENS*. This adds little complexity to the acronym, but immediately indicates when a patient's features lie towards the more generalised oculoauriculovertebral end of the phenotypic spectrum. PMID- 8471585 TI - TMJ performance and behaviour in patients more than 6 years after Le Fort I osteotomy. AB - Sixteen non cleft patients treated by one piece Le Fort I osteotomy were investigated for TMJ symptoms. Clinical examination and subjective assessment by the patients was used over a 6-year period. No increase in symptoms was recorded in the osteotomy group as compared to the general population, however, condylar atrophy was seen in two patients. Both of these patients were classified as high mandibular plane angle, with absolute mandibular retrognathism. This suggests that this group may be at greater risk of condylar atrophy. PMID- 8471586 TI - Perforating vessel(s) of the orbital floor: a cadaveric study. AB - Brisk haemorrhage is occasionally encountered in subperiosteal orbital floor exploration. Personal experience of the authors of a vessel perforating the orbital floor in a roughly similar position in a number of cases prompted further study. Twelve fresh cadavers (24 orbits) were dissected specifically to identify any vessel(s) perforating the orbital floor. In this study a vessel was identified in 83% of the dissections. PMID- 8471587 TI - Central giant cell granulomas of the jaws regress with calcitonin therapy. AB - Aggressive central giant cell granulomas may be eliminated by administering human calcitonin 0.5 mg (100 iu) deep subcutaneously for 1 year. This avoids the need for mutilating surgery or radiotherapy in growing children. Aggressive recurrent peripheral lesions (the giant cell epulis) can also be treated by excision after calcitonin therapy. These giant cell granulomas should be redefined as osteoclast granulomas, and the aneurysmal bone cyst, the cystic osteoclast granuloma. However the stimulus for the disturbance in the osteo progenitor spindle cell needs to be defined. PMID- 8471588 TI - A multiple dose comparison of ibuprofen and dihydrocodeine after third molar surgery. AB - The objectives were to compare the relative merits of ibuprofen 400 mg and dihydrocodeine 30 mg or 60 mg taken up to four times daily for up to 6 days in the treatment of pain after third molar removal. A randomised, double-blind, multiple dose, crossover study was undertaken in 68 patients undergoing two-stage bilateral lower third molar removal. The results showed that ibuprofen produced significantly greater analgesia than either of the dihydrocodeine treatments on the day of surgery. Ibuprofen and dihydrocodeine 60 mg produced significantly greater analgesia than dihydrocodeine 30 mg on the day after surgery, and on days 4 and 5 ibuprofen was again significantly superior to dihydrocodeine 60 mg. Roughly half the patients taking dihydrocodeine stopped the study on the day after surgery, because of adverse effects and/or inadequate relief, compared with 6 out of 44 taking ibuprofen. Dihydrocodeine 60 mg produced four times the number of patients affected by adverse effects compared with ibuprofen, and dihydrocodeine 30 mg three times as many. The principal adverse effects were nausea, vomiting and drowsiness. In conclusion, ibuprofen produced better analgesia than dihydrocodeine with significantly fewer adverse effects and is therefore a better choice for pain relief after oral surgery. PMID- 8471589 TI - A human T cell line engineered to secrete chimeric monoclonal antibody. AB - Both monoclonal antibodies (MAbs) and human T cells have been used in human tumor immunotherapy protocols. Tumor-infiltrating lymphocytes (TILs) and MAbs that can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) via human effector cells have shown antitumor effects in both animal models and clinical trials. One potential novel approach would be to combine these two modalities in the creation of a T cell capable of secreting antitumor immunoglobulins (Ig), in essence, creating an antitumor Ig "factory" at the tumor site. In the studies reported here, we have cloned the D612 MAb Ig genes and generated a chimeric D612 IgG1 containing the murine variable region and human constant region. D612 MAb has been shown to mediate lysis of human colon carcinomas via effector cell-mediated ADCC. We have demonstrated that following transfection, chimeric D612 can be expressed and secreted by the human T-cell line MOLT-4 at a rate of 0.25 micrograms/ml per 10(6) cells in 72 hours. The secreted Ig retained its antigen binding properties as assayed by competition radioimmunoassay and also its ability to mediate ADCC against human tumor cells. To our knowledge, this is the first demonstration of the production of a chimeric IgG by human T cells and opens the possibility of a therapeutic approach in which TILs secrete humanized antitumor MAb capable of mediating ADCC at the tumor site. PMID- 8471590 TI - Generation of T-cells reactive to the poorly immunogenic B16-BL6 melanoma with efficacy in the treatment of spontaneous metastases. AB - The B16-BL6 (BL6) melanoma is a poorly immunogenic murine tumor that is highly invasive and spontaneously metastasizes from the primary site. Utilizing an established anti-CD3/interleukin-2 (IL-2) culture procedure, we have previously reported that lymph nodes (LNs) draining immunogenic murine sarcomas contained preeffector cells that could be activated to differentiate into therapeutic effector cells for adoptive immunotherapy. By contrast, LNs draining the poorly immunogenic BL6 melanoma were found not to be a reliable source of preeffector cells. Instead, sensitization of preeffector cells reactive to BL6 required the subcutaneous inoculation of tumor admixed with Corynebacterium parvum. LN cells draining these vaccination sites demonstrated therapeutic efficacy only after subsequent anti-CD3/IL-2 activation. The sensitization of preeffector cells was dependent on the presence of tumor antigen and an optimal dose of C. parvum (< or = 50 micrograms). Furthermore, kinetic analysis revealed that the preeffector response was transient after tumor vaccination. The therapeutic efficacy of anti CD3/IL-2 activated LN cells was further evaluated in the treatment of spontaneous macroscopic BL6 visceral metastases. Spontaneous visceral metastases were induced in animals by inoculation with BL6 tumor in the footpad followed by amputation of the primary tumor 3 weeks later. The systemic transfer of 10(8) anti-CD3/IL-2 activated T-cells and the concomitant intraperitoneal administration of subtherapeutic doses of IL-2 1 week after amputation cured 50% of the animals and prolonged median survival time (MST) to > 140 days. All mice except one that received no treatment or was treated with IL-2 alone succumbed to visceral metastases with an MST of approximately 23 days. This study characterizes a model whereby the weak immune response to the BL6 melanoma can be positively or negatively modulated for the generation of antitumor reactive T-cells useful in adoptive immunotherapy. PMID- 8471591 TI - Tumor necrosis factor alpha and gamma-interferon enhancement of anti-epidermal growth factor receptor monoclonal antibody binding to human melanoma cells. AB - Previous studies have demonstrated that the expression of tumor-associated antigens can be regulated by cytokines. The purpose of this study was to determine whether tumor necrosis factor alpha (TNF alpha) and gamma-interferon (IFN gamma) were capable of modulating epidermal growth factor receptor (EGFr) immunorecognition on a human melanoma cell line in vitro. DX-3 melanoma cells treated for 24-72 h with various concentrations of each cytokine were incubated with an anti-EGFr monoclonal antibody (Mab) (A108) that recognizes an extracellular domain of the receptor, and differences in binding were analyzed by flow cytometry and radioimmunoassay. A dose- and time-dependent enhancement in EGFr immunorecognition was measurable in TNF alpha- and IFN gamma-treated cells. Combinations of these cytokines enhanced the recognition of EGFr on DX-3 cells to a level greater than that achieved with either TNF alpha or IFN gamma alone. Scatchard analysis of receptor binding curves revealed that there was no significant change in Mab affinity between control and cytokine-treated DX-3 melanoma cells, whereas a 1.5- to 1.8-fold enhancement in the number of Mab binding sites was measurable in TNF alpha- and IFN gamma-treated cells, respectively, when compared with controls. Immune complex kinase assay of EGFr showed threefold higher tyrosine kinase activity in TNF alpha-treated cells, but no change in kinase activity was observed following IFN gamma treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471592 TI - Immunomodulatory effects of interferon-gamma in patients with metastatic malignant melanoma. AB - Interferon-gamma (IFN-gamma) is a potent monocyte/macrophage activating agent that in animal models exhibits a bell-shaped dose-response curve of immunomodulatory activity and antitumor efficacy. Previous clinical trials of IFN gamma conducted at the maximal tolerated dose (MTD) have been associated with low response rates that may have been due to failure to treat at an optimal immunomodulatory dose (OID). The objective of this study was to test the hypothesis that optimal immunomodulatory activity of IFN-gamma in patients with metastatic melanoma would be obtained at a dose below the MTD. Groups of five patients each were given daily subcutaneous injections of IFN-gamma at doses of 0.01, 0.1, or 0.25 mg/m2. In vivo immunomodulation was assessed by serial measurement of serum neopterin and by flow cytometry. IFN-gamma doses of 0.1 or 0.25 mg/m2 induced significantly greater immunomodulation of monocyte-associated immune parameters than 0.01 mg/m2. Changes in immunologic parameters included marked elevation of serum neopterin levels, significant increases in monocyte expression of CD64, beta 2-microglobulin, and HLA-ABC, and decreased monocyte expression of CD14. The most dramatic decreases in CD14 expression were observed on monocytes obtained from patients treated at 0.25 mg/m2. The 0.25-mg/m2 dose group had significantly lower white blood cell counts on day 14. No bell-shaped curve of immunologic response was observed over the dosage range tested. Based on the similarity of the immunologic effects at 0.1 and 0.25 mg/m2, treatment at the MTD of IFN-gamma (0.25 mg/m2) represents treatment at the OID for patients with metastatic malignant melanoma. PMID- 8471593 TI - Pharmacodynamics of biological response in vivo after single and multiple doses of interferon-beta. AB - Interferons (IFNs) induce gene regulation in vivo that may be used to identify effective doses, schedules, and potential correlates of therapeutic response. To critically examine minimum effective dose, duration of response, and cumulative effects of repetitive doses, a range of subcutaneous doses of IFN beta ser was studied in 32 healthy human volunteers. IFN-induced products of gene regulation assessed were beta 2-microglobulin, neopterin, and tryptophan in serum and 2',5' oligoadenylate (2-5A) synthetase activity in peripheral blood mononuclear cells. Eight subjects per group received 0.09, 0.9, 9, or 45 MU of IFN beta. Responses were measured at 24, 48, and 72 h after single and multiple doses. The lowest biologically effective dose was 0.9 MU; significant (p < 0.02) increases were observed at 24 h in beta 2-microglobulin and cellular 2-5A synthetase activity. At the two higher doses, 9 and 45 MU, changes were observed at 24 h in all products (p < 0.01). A dose response (p < 0.01) over the range of 0.09-45 MU was observed for all these serum and intracellular gene products. Changes in neopterin, beta 2-microglobulin, and cellular 2-5A synthetase correlated significantly with each other. The response to a single dose of IFN beta was as great in magnitude as the response to multiple doses, suggesting an alternate-day schedule would maintain biological response. PMID- 8471594 TI - Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma. AB - XOMAZYME-Mel (XMMME-001-RTA) is an immunoconjugate comprised of ricin A chain conjugated to a murine monoclonal antibody directed against high molecular weight melanoma antigens. Although not necessarily related to increased toxicity or decreased efficacy, the development of anti-immunoconjugate antibodies may limit repetitive dosing with an immunoconjugate. We evaluated the role of cyclosporine A in blocking the antibody response in patients with melanoma treated with XMMME 001-RTA. Patients received cyclosporine in divided daily doses to achieve serum levels by HPLC of 150-200 ng/ml on days 1-22. On day 3, XMMME-001-RTA was begun at dosages 0.2-0.6 mg/kg daily for 5 days. Treatment was repeated every 35 days. Three patients were treated in each dosage tier (0.2, 0.4, 0.6 mg/kg). Nine patients were entered and all nine were evaluable. Patients had histologically confirmed melanoma. Metastatic sites included skin, soft tissue, and lymph nodes (seven), lung (two), liver (one), and spleen (one). There were four men and five women aged 46-75 years. Toxicities included myalgia, arthralgia, hypoalbuminemia, fatigue, elevations in liver function tests, and increased peripheral edema. Four patients received two to five repeated dosages of XMMME-001-RTA. One wheal-and flare reaction from an immunotoxin test dose of XMMME-001-RTA was noted after five cycles. After a test dose subsequent to one cycle, two patients experienced chest tightness without ECG changes and were removed from the study. All toxicities resolved without sequelae. One patient experienced partial lymph node remission for 9 months. A second patient had stable mediastinal disease for 20 months. XMMME-001-RTA is safe when given repeatedly with cyclosporine. PMID- 8471595 TI - Adverse reactions to intravenous contrast media in patients treated with interleukin-2. AB - Seventy patients consecutively admitted to a single institution were treated with high-dose interleukin-2 (IL-2) and analyzed for determining the incidence and risk factors associated with reactions to i.v. contrast media. Patients with metastatic renal cancer (n = 44) or melanoma (n = 26) received 74 cycles of IL-2 administered at 2 to 6 x 10(6) U/m2/d for 10-21 days either alone or with lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TILs). Seventy-four computed tomography (CT) scans were performed before administration of IL-2; and 74, 59, and 35 CT scans were performed, respectively, 2, 6, and 10 weeks after administration of IL-2. Of the 168 scans performed after therapy with IL-2, non-ionic media were used in 110 and ionic media were used in 58. There were no reactions before administration of IL-2, but there were nine reactions after therapy with IL-2. Reactions to contrast media occurred 1-4 hours after media infusion and included fever, chills, emesis, diarrhea, rash, wheezing, hypotension, edema, and oliguria. Hospitalization was required in seven cases, including intensive care unit support in four, but all patients recovered fully. Contrast reactions were more frequent 2 weeks after therapy with IL-2 (eight of 74 scans, 11%) compared with 6 weeks after IL-2 (one of 59 scans, 1.7%), but the difference was not statistically significant (McNemar's test). Six patients who reacted to contrast 2 weeks after IL-2 treatment received contrast 4 weeks later: five had no reaction and only one experienced a reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471596 TI - Adoptive chemoimmunotherapy for the treatment of relapsed and refractory solid tumors using ex vivo activated memory T cells (autolymphocyte therapy) and cyclophosphamide. AB - Autolymphocytes (ALT cells) are ex vivo activated peripheral blood lymphocytes (PBL) from tumor-bearing hosts (TBH) that consist primarily of tumor specific CD45RO+ (memory) T cells. These ALT cells combined with cimetidine as autolymphocyte therapy (ALT) have previously been demonstrated to be a safe and active form of outpatient adoptive immunotherapy (AIT) in human TBH with metastatic renal cell cancer (RCC). To determine activity of ALT in human TBH with therapy-resistant solid tumors other than RCC and whether it was feasible to combine ALT with chemotherapy, we studied 21 patients with relapsed or primary refractory solid tumors following a study protocol of adoptive chemoimmunotherapy (ACIT) using ALT and cyclophosphamide. Twenty patients were evaluable. Five responses were seen, including two complete responses (CRs) and three partial responses (PRs). ACIT activity was noted in relapsed TBH who had responded to their previous chemotherapy and/or radiation therapy. The toxic effects of this ACIT study were minimal with no treatment-related morbidity or mortality. It appears that in some relapsed but not primary refractory solid tumors, ACIT using ALT (CD45RO+ T cells and cimetidine) together with cyclophosphamide has definite antitumor activity associated with little or no toxic effects. Further studies of ACIT in solid tumors other than RCC are justified. PMID- 8471597 TI - An acetylcholine receptor regulatory site in BC3H1 cells: characterized by laser pulse photolysis in the microsecond-to-millisecond time region. AB - When a neurotransmitter binds to its specific receptor, the protein forms transmembrane channels through which ions flow, leading to changes in transmembrane voltage that trigger signal transmission between neurons. How do inhibitors affect this process? Interesting and extensive information comes from investigations of the acetylcholine receptor, the best known of these proteins. This receptor is inhibited by cationic inhibitors, including local anesthetics, and acetylcholine at high concentrations. The accepted mechanism, elegant in its simplicity, is that these compounds enter the receptor-channel after it opens and block inorganic ion flux. This mechanism requires that the inhibitors affect only the apparent rate constant for channel closing (k'cl). An alternative mechanism invokes a specific regulatory (inhibitory) site to which inhibitors bind before the channel opens and the signal is transmitted. This mechanism requires that the inhibitors affect the apparent rate constants for both channel opening (k'op) and closing. The effect of inhibitors on k'op has not been determined previously. This report describes the use of a newly developed laser-pulse photolysis technique with a dead time of approximately 120 microseconds to determine the effect of a local anesthetic, procaine, one of the best studied cationic inhibitors of the acetylcholine receptor, on both k'op and k'cl. Both k'op and k'cl were found to decrease with increasing procaine concentration. This effect of the inhibitor of k'op cannot be explained by the open-channel-blocking mechanism but is consistent with the existence of a regulatory (inhibitory) receptor site. PMID- 8471598 TI - The energetics and cooperativity of protein folding: a simple experimental analysis based upon the solvation of internal residues. AB - The reversible unfolding of two dissimilar proteins, phosphoglycerate kinase from Bacillus stearothermophilus (PGK) and Staphylococcus aureus nuclease (SAN), was induced with two denaturants, urea and guanidinium chloride (GuHCl). For each protein, structural transitions were monitored by intrinsic fluorescence intensity changes arising from a unique tryptophan residue. In the case of SAN the single, native tryptophan residue was used, whereas for PGK two versions, one with a tryptophan at position 315 and one at 379, were constructed genetically. The resultant folding curves were analyzed by considering the change in the solvation free energy of internal amino acid residues as the denaturant concentration was varied. We derive the following simple relationship: -RT ln K = delta Gw + n delta Gs,m[D]/Kden. + [D]) where K is the equilibrium constant describing the distribution of folded and unfolded forms at a given denaturant concentration [D], delta Gw is the free energy change for the transition in the absence of denaturant, and n is the number of internal side chains becoming exposed. delta Gs,m and Kden. are constants derived empirically from the solvation energies of model compounds and represent the behavior of an average internal side chain between 0 and 6 M GuHCl and 0 and 8 M urea. For proteins of known structure these values can easily be derived, and for others, average values in guanidinium chloride (delta Gs,m = 0.775 kcal/mol and Kden. = 5.4 M) or urea (delta Gs,m = 1.198 kcal/mol and Kden. = 25.25 M) can be used in the analysis. Results show that the parameters n and delta Gw are independent of the denaturant used for all 12 transitions studied. This supports the hypothesis that the unfolding activity of urea and GuHCl can be accounted for by their effect on the solvation energy of amino acid side chains which are buried in the folded but exposed in the unfolded protein. This simple analytical treatment allows the "cooperativity" of protein folding to be interpreted in terms of the number of side chains becoming exposed to the solvent in a given step and allows accurate estimation of the free energy irrespective of the denaturant concentration needed to induce the transition. PMID- 8471599 TI - Subunit interactions provide a significant contribution to the stability of the dimeric four-alpha-helical-bundle protein ROP. AB - Detailed thermodynamic and spectroscopic studies were carried out on the ColE1 ROP protein in order to establish a quantitative basis for the contribution of noncovalent interactions to the stability of four-helix-bundle proteins. The energetics of both heat- and GdnHCl-induced denaturation were measured by differential scanning microcalorimetry (DSC) and/or by following the change in circular dichroism in the far-UV range. Sedimentation equilibrium analyses were performed to characterize the state of aggregation of the protein. No intermediate species could be detected during thermal unfolding of the dimer in the absence of GdnHCl. Under these conditions ROP unfolding exhibits a strict two state behavior. The thermodynamic parameters for the reaction N2<->2D are delta HD = 580 +/- 20 kJ.(mol of dimer)-1, delta Cp = 10.3 +/- 1.3 kJ.(mol of dimer) 1.K-1, and Tm = 71.0 +/- 0.5 degrees C. The corresponding Gibbs energy change of unfolding is delta GD degree = 71.7 kJ.(mol of dimer)-1 at 25 degrees C and pH 6. In the presence of 2.5 M GdnHCl, however, ROP dissociates into monomers at elevated temperatures, as the loss of the concentration dependence of Tm and the decreased molecular weight demonstrate. The corresponding transition parameters are delta HD (2.5 M GdnHCl) = 130 +/- 10 kJ.(mol of monomer)-1 and Tm = 51.6 +/- 0.3 degrees C. Isothermal unfolding studies at 19 degrees C using GdnHCl as denaturant yielded a Gibbs energy change of unfolding of 22.4 kJ.(mol of monomer) 1. This extrapolated value is 38% lower than the corresponding delta GD degree value of 35.85 kJ.(mol of monomer)-1 calculated from thermal unfolding for the monomer in the absence of GdnHCl, where the protein is known to be a dimer. These results suggest that subunit interactions are an important source of stabilization of the native four-helix-bundle structure of ROP. PMID- 8471600 TI - Aggregation and denaturation of apomyoglobin in aqueous urea solutions. AB - The effects of urea on apomyoglobin solubility have been investigated. Apomyoglobin precipitation was found to be a thermodynamically reversible process independent of the pathway of aggregation. A liquid-solid phase diagram was constructed for the precipitation of apomyoglobin as a function of urea and protein concentration. Apomyoglobin solubility decreases by an order of magnitude between 0 and 1.5 M urea, reaching a minimum near 2.4 M urea and increasing at higher urea concentrations (the denaturation midpoint is at approximately 2.6 M urea). This decrease in protein solubility is opposite to that expected based on amino acid solubilities, since both polar and nonpolar molecules become more soluble with increasing urea concentration. Solubility minima for proteins have been rationalized in terms of folding intermediates. However, our structural studies show no evidence for folding intermediates in apomyoglobin under the experimental conditions, apart from small predenaturation changes. Our data are consistent with an alternative hypothesis, namely, that the primary aggregating species are denatured protein molecules, rather than intermediate states. Consistent with recent thermodynamic and statistical mechanical models, the solubility minimum may be described as the result of two competing effects of urea: (1) urea denatures the protein, and (2) urea makes the solvent more favorable for the native and any denatured state. At low urea concentration, solubility decreases with increasing urea concentration due to the domination of the solubility behavior by the increase in the population of aggregation competent (denatured) protein molecules. However, at high urea concentration, the increasingly favorable nature of the solvent dominates, resulting in increasing solubility with urea concentration. The phase diagram provides guidance for the best experimental conditions (pathway) to use to avoid aggregation during the refolding of denaturant-unfolded protein. PMID- 8471601 TI - Crystallographic analysis of substrate binding and catalysis in dihydrolipoyl transacetylase (E2p). AB - The catalytic domain of dihydrolipoyl transacetylase (E2pCD) forms the core of the pyruvate dehydrogenase multienzyme complex and catalyzes the acetyltransferase reaction using acetylCoA as acetyl donor and dihydrolipoamide (Lip(SH)2) as acceptor. The crystal structures of six complexes and derivatives of Azotobacter vinelandii E2pCD were solved. The binary complexes of the enzyme with CoA and Lip(SH)2 were determined at 2.6- and 3.0-A resolutions, respectively. The two substrates are found in an extended conformation at the two opposite entrances of the 30 A long channel which runs at the interface between two 3-fold-related subunits and forms the catalytic center. The reactive thiol groups of both substrates are within hydrogen-bond distance from the side chain of His 610. This fact supports the indication, derived from the similarity with chloramphenicol acetyl transferase, that the histidine side chain acts as general base catalyst in the deprotonation of the reactive thiol of CoA. The conformation of Asn 614 appears to be dependent on the protonation state of the active site histidine, whose function as base catalyst is modulated in this way. Studies on E2pCD soaked in a high concentration of dithionite lead to the structure of the binary complex between E2pCD and hydrogen sulfite solved at 2.3-A resolution. It appears that the anion is bound in the middle of the catalytic center and is therefore capable of hosting and stabilizing a negative charge, which is of special interest since the reaction catalyzed by E2pCD is thought to proceed via a negatively charged tetrahedral intermediate. The structure of the binary complex between E2pCD and hydrogen sulfite suggests that transition-state stabilization can be provided by a direct hydrogen bond between the side chain of Ser 558 and the oxy anion of the putative intermediate. In the binary complex with CoA, the hydroxyl group of Ser 558 is hydrogen bonded to the nitrogen atom of one of the two peptide-like units of the substrate. Thus, CoA itself is involved in keeping the Ser hydroxyl group in the proper position for transition state stabilization. Quite unexpectedly, the structure at 2.6-A resolution of a ternary complex in which CoA and Lip(SH)2 are simultaneously bound to E2pCD reveals that CoA has an alternative, nonproductive binding mode. In this abortive ternary complex, CoA adopts a helical conformation with two intramolecular hydrogen bonds and the reactive sulfur of the pantetheine arm positioned 12 A away from the active site residues involved in the transferase reaction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8471603 TI - Determinants of protein thermostability observed in the 1.9-A crystal structure of malate dehydrogenase from the thermophilic bacterium Thermus flavus. AB - A binary complex of malate dehydrogenase from the thermophilic bacterium Thermus flavus (tMDH) with NADH has been crystallized from poly(ethylene glycol) 3500, pH 8.5, yielding diffraction-quality crystals in space group P2(1)2(1)2(1). The structure was solved at 1.9-A resolution using molecular replacement and refined to an R factor of 15.8% with good geometry. The primary sequence of tMDH is 55% identical to that of cytoplasmic malate dehydrogenase (cMDH) [Birktoft, J. J., Rhodes, G., & Banaszak, L. J. (1989) Biochemistry 28, 6065-6081], and overall their three-dimensional structures are very similar. Like cMDH, tMDH crystallized as a dimer with one coenzyme bound per subunit. The coenzyme binds in the extended conformation, and most of the interactions with enzyme are similar to those in cMDH. In tMDH, small local conformational changes are caused by the replacement of a glutamic acid for the aspartic acid involved in hydrogen bonding to the adenine ribose of NADH. Comparison of tMDH with cMDH reveals that both tMDH subunits more closely resemble the B subunit of cMDH which therefore is the more likely representative of the solution conformation. While cMDH is inactivated at temperatures above about 50 degrees C, tMDH is fully active at 90 degrees C. On the basis of the X-ray crystal structure, a number of factors have been identified which are likely to contribute to the relative thermostability of tMDH compared to cMDH. The most striking of the differences involves the introduction of four ion pairs per monomer. All of these ion pairs are solvent accessible. Three of these ion pairs are located in the dimer interface, Glu27 Lys31, Glu57-Lys168, and Glu57-Arg229, and one ion pair, Glu275-Arg149, is at the domain interface within each subunit. Additionally, we observe incorporation of additional alanines into alpha-helices of tMDH and, in one instance, incorporation of an aspartate that functions as a counterchange to an alpha-helix dipole. The possible contributions of these and other factors to protein thermostability in tMDH are discussed. PMID- 8471602 TI - Structure of the cobalt-dependent methionine aminopeptidase from Escherichia coli: a new type of proteolytic enzyme. AB - The X-ray structure of Escherichia coli methionine aminopeptidase (MAP) has been determined to 2.4-A resolution and refined to a crystallographic R-factor of 18.2%. The fold is novel and displays internal pseudo-2-fold symmetry which structurally relates the first and second halves of the polypeptide chain. The topology consists of a central antiparallel beta-sheet covered on one side by two pairs of alpha-helices and by a C-terminal loop. The other face of the beta sheet, together with some irregular loops, forms the active site, which contains two cobalt ions 2.9 A apart. These metal ions are liganded by the side chains of Asp 97, Asp 108, Glu 204, Glu 235, and His 171 with approximate octahedral coordination. In terms of both the novel backbone fold and the constitution of the active site, MAP appears to represent a new class of proteolytic enzyme. PMID- 8471604 TI - Structure of chicken annexin V at 2.25-A resolution. AB - The crystal structure of chicken annexin V has been solved by molecular replacement and refined at 2.25 A. The final R factor is 19.7% with good geometry. The chicken annexin V structure is very similar to the human annexin V structure, with four similar domains each containing five helices. The structure includes three calcium ions in domains I, II, and IV, each bound by the characteristic K-G-X-G-T-(38 residues)-D/E motif. In view of the structural similarity between human and chicken annexin V, we suggest that they have a common vital function which developed early in evolutionary history. PMID- 8471605 TI - Dynamic light scattering studies of alpha IIb beta 3 solution conformation. AB - The prototypical integrin receptor, alpha IIb beta 3, isolated from the membrane fraction of human blood platelets by solubilization in Triton X-100 (reduced) and affinity chromatography on lentil lectin-agarose, has been further purified by gel filtration chromatography in octyl glucoside to obtain the intact receptor complex in a form suitable for hydrodynamic measurements. The molecular weight [(6.0 +/- 0.2) x 10(3)] and Stokes radius (2.3 +/- 0.1 nm) of detergent micelles formed in 0.03 M octyl glucoside have been determined by classical light scattering intensity and dynamic light scattering measurements, respectively. An algorithm has been developed which explicitly considers the contribution of detergent micelles to the intensity autocorrelation function of particles suspended in detergent. This procedure has been validated with polystyrene particles of known radius, as well as with the soluble protein fibrinogen. Application of these procedures to dynamic light scattering data obtained with alpha IIb beta 3 resulted in a translational diffusion coefficient (Dto(20,w)) of (2.78 +/- 0.31) x 10(-7) cm2 s-1, corresponding to a Strokes radius (Rs) of 7.67 +/- 0.85 nm for the integrin/octyl glucoside complex. Light scattering intensity measurements gave a molecular weight of (2.26 +/- 0.22) x 10(5) for the polypeptide moiety of the complex, in excellent agreement with the 2.28 x 10(5) value calculated from primary structure data. As a spherical, hydrated alpha IIb beta 3 complex, with bound detergent, would exhibit a Stokes radius of approximately 5 nm, these data indicate considerable asymmetry in the solution conformation of alpha IIb beta 3. PMID- 8471606 TI - Calorimetric and spectroscopic studies of the interaction of Manduca sexta apolipophorin III with zwitterionic, anionic, and nonionic lipids. AB - The nature of the interaction of apolipophorin III (apoLp-III) from the insect Manduca sexta with a variety of zwitterionic and anionic phospholipids and with several nonionic glycolipids was investigated by differential scanning calorimetry (DSC) and 31P-NMR spectroscopy. Monoglucosyldiacylglycerol, phosphatidylethanolamine, and phosphatidic acid (pH 7.2) appear to exhibit the weakest interaction with apoLp-III. DSC studies revealed that the gel/liquid crystalline phase transition of these lipids is little affected by the binding of apoLp-III. Diglucosyldiacylglycerol, phosphatidylcholine (PC), phosphatidylserine, and phosphatidic acid (pH congruent to 8.8) seem to exhibit somewhat stronger interactions with apoLp-III. The binding of apoLp-III to these lipids induces the formation of lipid domains which melt less cooperatively and at higher temperatures than do the pure lipid dispersions, while having little effect on the melting enthalpy of lipid hydrocarbon chains. Phosphatidylglycerol (PG) and phosphatidic acid (pH > 9.3) appear to exhibit the strongest interactions with apoLp-III. The binding of apoLp-III to these lipids severely disrupts their bilayer structure, resulting in marked reductions in the cooperativity and enthalpy of the gel/liquid-crystalline phase transition of the lipids. Studies of binary mixtures of PC and PG indicate that such bilayer disrupting interactions only occur in the presence of nonphysiologically high concentrations of PG. The binding of apoLp-III to binary mixtures of diacylglycerol and zwitterionic phospholipid has little effect on the chain melting or the bilayer/nonbilayer phase transitions of these lipids, but it appears to promote the retention of water at the surface of the lipid aggregate. Our results indicate that the binding of apoLp-III to lipid bilayers is mediated primarily through polar and/or ionic interactions at the lipid bilayer surface. Our results also suggest that the interaction of apoLp-III with lipid bilayers promotes the hydration of their surfaces, a property which is consistent with the proposed in vivo functions of this protein. PMID- 8471607 TI - Cooperativity during multiple phosphorylations catalyzed by rhodopsin kinase: supporting evidence using synthetic phosphopeptides. AB - Rhodopsin kinase is a key component in the shutdown of visual transduction. The phosphorylation of rhodopsin's C-terminus was evaluated using synthetic peptides derived from the last 12 amino acids (337-348) as substrates and their phosphorylated counterparts as inhibitors. It was found that synthetic peptides were phosphorylated at the serine residue corresponding to Ser-343 in the primary sequence of bovine rhodopsin. The phosphopeptides were prepared by incorporating into the peptide chain a trityl-protected serine derivative at the site destined to contain the phosphoryl group. The trityl group was selectively released with 20% (v/v) dichloroacetic acid; the free hydroxyl group was then phosphitylated with di-tert-butyl N,N-diethylphosphoramidite, and the resulting phosphite derivative was oxidized with m-chloroperoxybenzoic acid. The phosphopeptides were found to have a greater affinity for the kinase compared with their nonphosphorylated counterparts; for the peptides corresponding to residues 337 348 of rhodopsin the affinity increased in the order VSKTETSQVAPA < VSKTETS[PO3H2]QVAPA < VS[PO3H2]KTETS[PO3H2]QVAPA. The results are interpreted to support the cooperativity hypotheses proposed previously [Wilden, U., & Kuhn, H. (1982) Biochemistry 21, 3014-3022; Aton, B. R., Litman, B. J., & Jackson, M. L. (1984) Biochemistry 23, 1737-1741]. PMID- 8471608 TI - 13C NMR studies of the enzyme-product complex of Bacillus subtilis chorismate mutase. AB - The chorismate mutase reaction is a rare enzyme-catalyzed 3,3-sigmatropic rearrangement of chorismate to prephenate. Bacillus subtilis chorismate mutase was overproduced and purified from Escherichia coli XL1-Blue (pBSCM2) using a modification of the procedure of Gray et al. (Gray, J. V., Grolinelli-Pimpaneau, B., & Knowles, J. R. (1990) Biochemistry 29, 376-383); the modification leads to minimal contaminating prephenate dehydratase activity (< 0.001%). The native molecular mass of B. subtilis chorismate mutase was determined by gel filtration to be approximately 44 kDa, indicative of a homotrimer of the 14.5-kDa subunits as determined by electrospray mass spectrometry. 13C NMR was used to study the structure of [U-13C]prephenate bound at the active site of B. subtilis chorismate mutase. All the enzyme-bound 13C NMR resonances of [U-13C]prephenate were assigned, and where possible, 1JC,Cs were quantified; [1,3,5,8-13C]prephenate and [2,6,9-13C]prephenate, prepared respectively from [1,3,5,8-13C]chorismate and [2,6,9-13C]chorismate, aided the 13C NMR resonance assignments. Enzyme-bound prephenate exhibits remarkably different chemical shifts relative to free prephenate; the chemical shift changes range from -6.6 ppm for the C6 resonance to 5.6 ppm for the C5 resonance, suggesting a strong perturbation of the C5-C6 bond. 13C NMR studies of model compounds at various pH values and in various solvents suggest that the observed 13C chemical shift changes of enzyme-bound prephenate cannot be rationalized solely on the basis of changes in the pKas of the carboxylic acid groups or hydrophobic solvation at the active site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471609 TI - Phenylhydrazones as new good substrates for the dioxygenase and peroxidase reactions of prostaglandin synthase: formation of iron(III)-sigma-phenyl complexes. AB - Phenylhydrazones of various aromatic and aliphatic aldehydes or ketones act as good substrates of the dioxygenase reaction of prostaglandin synthase (PGHS). Corresponding alpha-azo hydroperoxides are formed as intermediates with maximum initial rates of O2 consumption between 8 and 230 mol (mol of PGHS)-1 s-1 for benzophenone and hexanal phenylhydrazone, respectively. The Km values for these reactions vary from 100 to 300 microM. These alpha-azo hydroperoxides are then converted to the corresponding alpha-azo alcohols by the peroxidase reaction of PGHS. During such oxidations of phenylhydrazones by PGHS, a new complex of this hemeprotein characterized by peaks at 438 and 556 nm is formed. This complex was obtained both by direct reaction of PGHS Fe(III) with phenyldiazene and by reaction of PGHS Fe(III) with phenylhydrazine in the presence of O2. By analogy to results previously reported for hemoglobin, myoglobin, catalase, and cytochrome P450, this species should be a sigma-phenyl PGHS FeIII-Ph complex. The PGHS FeIII-Ph complex should derive from an oxidation of the intermediate alpha azo alcohol by PGHS Fe(III), cleavage of the resulting alkoxy radical with formation of a ketone (or aldehyde) and Ph*, and combination of PGHS Fe(II) with Ph*. Such an oxidation of alpha-azo alcohols by lipoxygenase-FeIII with formation of Ph* was reported previously. The formation of Ph* and of PGHS FeIII-Ph is likely the cause of the inhibitory effects previously reported for arylhydrazones toward PGHS. PMID- 8471610 TI - Glycosphingolipid backbone conformation and behavior in cholesterol-containing phospholipid bilayers. AB - 2H NMR spectroscopy was used to consider correspondence between existing single crystal X-ray data for glycosphingolipids and their ceramide backbone conformation in fluid phospholipid membranes. A monoglycosylated sphingolipid, glucosylceramide (GlcCer), which represents the core structure of many important glycosphingolipids, was derived by partial synthesis through replacement of all native fatty acids with the 18-carbon species, stearic acid, deuterated at C2. N [2,2-2H2]stearoyl-GlcCer was used to probe glycosphingolipid orientation and motion at low concentration in "fluid" phospholipid bilayers composed of dimyristoylphosphatidylcholine (DMPC), with and without physiological amounts of cholesterol. Spectral analysis, aided by stereoselective monodeuteration of the GlcCer fatty acid at C2, demonstrated that glycosphingolipid average acyl chain backbone conformation in fluid phospholipid membranes, with or without cholesterol, is likely closely related to that predicted from single crystal X ray studies [Pascher, I. (1976) Biochim. Biophys. Acta 455, 433-451; Pascher, I., & Sundell, S. (1977) Chem. Phys. Lipids 20, 175-191]. To test the generality of this observation, specific comparisons were made involving galactosylceramide (GalCer) and globoside. GalCer provided a glycolipid differing only in monosaccharide stereochemistry (galactose vs glucose). Globoside permitted isolation of the effect of headgroup size, since it is derived from GlcCer via extension of the carbohydrate portion by the oligosaccharide, GalNAc beta 1- >3Gal alpha 1-->4Gal attached in beta 1-->4 linkage to the Glc residue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471611 TI - Myosin thick filaments and subunit exchange: a stochastic simulation based on the kinetics of assembly. AB - Subunit exchange between groups of myosin filaments at equilibrium in a volume similar to a sarcomere is simulated using Monte Carlo (probabilistic) methods. Five published kinetic parameters (three rate constants and two cooperativity parameters) which govern the assembly of thick filaments from purified myosin at pH 8.0 are used for the computations. Filament length distributions equivalent to those measured experimentally in the electron microscope result. Distinctive patterns of exchange emerge because cooperativity in myosin assembly is not confined to nucleation but functions throughout growth. Fluctuations in filament size, first apparent in the millisecond time domain, mediate exchange which first occurs at the tips of the filaments and then gradually progresses inwards toward the central bare-zone. Exchange rates decreased by an approximate factor of 10 per decade of time: full exchange takes years, 50% takes 28 h, and 10% takes a brief 100 ms. These data represent the fastest possible rates of exchange because synthetic myosin filaments lack the overall stabilizing influence of the copolymerizing proteins of native filaments. Exchange at equilibrium is therefore too slow to explain, for example, the much faster rates recorded in vivo for the complete replacement of one myosin isoform by another. Facilitated exchange where partial or complete filament dissociation is followed by the introduction of new subunits during reassembly offers a means of accelerating exchange. In this context, it is shown that the requisite disassembly and reassembly of myosin thick filaments can be completed in a minimum of a few seconds. PMID- 8471612 TI - Identification of structural features involved in binding of alpha-amanitin to a monoclonal antibody. AB - Twenty-four derivatives of the cyclic octapeptide alpha-amanitin were assayed for their affinities to the monoclonal antibody beta A1/1. The derivatives were of natural, semisynthetic, and synthetic origin and had KD values ranging from 2 nM to > 70 microM. In the majority of the derivatives the chemical modifications had no detectable influence on the overall shape of the double-ring peptide. Given this condition, binding factors could be calculated from KD values of the amatoxin derivatives, which were valid for all amatoxins for estimating the contribution made by single structures to complex formation. The complex between alpha-amanitin and the immunoglobulin involves at least eight sites of contact. Four of them are responsible for strong interactions: (1) the OH group of hydroxyproline2 (binding factor 413), (2) the lipophilic side chain of isoleucine6 (binding factor 131), (3) the -CH2- moiety of the adjacent glycine5 or the absence of a side chain in this position (binding factor 361), and (4) the proton at the indole nitrogen of hydroxytryptophan4 (binding factor 140). The residual four interactions are hydrogen bonds of lower strength corresponding to binding factors of 1.5-8. The key role of the unique conformation of the amatoxins in determining their binding properties was shown by two amatoxin derivatives in which changes in the conformation were associated with virtually complete loss of affinity. For all amatoxin derivatives with conformations similar or identical to that of alpha-amanitin, we found empirical evidence that those structures of the peptide involved in binding make their contributions virtually independent of each other. It is a consequence of this rule that structural features that cooperate in binding could be characterized by the numerical product of their binding factors. PMID- 8471613 TI - Porcine cerebroside sulfate activator: further structural characterization and disulfide identification. AB - Cerebroside sulfate activator (CS-Act) is a small compact protein which binds and solubilizes certain glycosphingolipids. Following the recent publication of the purification and preliminary sequence of pig kidney CS-Act [Fluharty, A.L., Katona, Z., Meek, W.E., Frei, K., & Fowler, A.V. (1992) Biochem. Med. Metab. Biol. 47, 66-85], we now report the primary sequence of the C-terminal portion of this protein and the assignment of the three disulfide bonds. Cyanogen bromide (CNBr) treatment of native CS-Act produced three major and several minor peptide fragments. Analysis of one HPLC-purified fragment revealed the C-terminus 14 amino acid sequence. This established the length of the native protein at 79 residues. In conjunction with the sequence data for one other major HPLC-purified CNBr fragment, it could be concluded that the three intrachain disulfide bonds were located at half-cystine residues 4 and 77, 7 and 71, and 36 and 47. Mass spectrometry (fast atom bombardment and electrospray ionization) showed the molecular weight of the major component of the CS-Act preparation to be 9720.5 Da, which was in close agreement with the calculated mass of the 79 amino acid peptide with five covalently attached sugar residues and three internal disulfide bonds. The mass spectrometric molecular weight measurements also showed that the CS-Act preparation possessed microheterogeneity in its carbohydrate moiety, as less intense signals corresponded to species containing (in decreasing order of abundance) two, one, four, and three sugar residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471614 TI - Treatment with a polyamine analog alters DNA-matrix association in HeLa cell nuclei: a nucleoid halo assay. AB - The polyamine analog 1,14-bis(ethylamino)-5,10-diazatetradecane (BE-4-4-4) depletes polyamines and inhibits the growth of tumor cells in tissue culture. We treated HeLa cells in culture with BE-4-4-4 for different time periods to produce different degrees of polyamine depletion. The cells were lysed and dehistonized to obtain nucleoids containing DNA attached to the nuclear matrix. Titration of the nucleoids with propidium iodide caused an uncoiling of negatively supercoiled DNA, resulting in the formation of a halo surrounding the nucleoid periphery. The halo diameters in both the BE-4-4-4-treated cells and the untreated control cells were measured using a fluorescence image analysis system. As compared to the control cells, the BE-4-4-4-treated cells showed a 20-25% decrease in halo diameter, indicating that there was less relaxation of the negative supercoils in the nuclear DNA of the BE-4-4-4-treated cells than in the controls. PMID- 8471615 TI - Conditions for the stability of the B, C, and Z structural forms of poly(dG-dC) in the presence of lithium, potassium, magnesium, calcium, and zinc cations. AB - The occurrence of alternative structures for the lithium, sodium, and potassium salts of poly(dG-dC) was determined as a function of hydration using IR spectra of nonoriented gels. Poly(dG-dC).K with added KCl (r = 0.56 where r is the moles of KCl per mole of nucleotide residue) gave results essentially identical to the much studied poly(dG-dC).Na with added NaCl (r = 0.56). Both gave a sharp transition from a unique B structure (hereafter designated B*) to the Z structure upon dehydration. Poly(dG-dC).Li with added LiCl (r = 0.36) assumed the B* structure at high hydration but made a broad transition to the C structures as hydration was lowered. We believe this is the first clear evidence of the C structure for poly(dG-dC). No other structures (A, D, or Z) were observed at any hydration in nonoriented gels. Poly(dG-dC).Na with added ZnCl2 (r = 0.2) existed as a mixture of the B* and Z structures in maximally hydrated gels. A broad, incomplete transition to a higher mole fraction of Z structure occurred upon dehydration. Zn2+ promotes the Z structure for poly(dG-dC) and appears to bind to guanine residues. Poly(dG-dC).Na with added MgCl2 or CaCl2 (r = 0.2) assumed the normal B* structure at maximum hydration with no hint of Z structure. Slight dehydration produced a very sharp transition to the Z structure. Both Mg2+ and Ca2+ are strong promoters of the Z structure but do not bind to cytosine or guanine residues. PMID- 8471616 TI - Formation of DNA-protein cross-links in mammalian cells by levuglandin E2. AB - Levuglandin E2 (LGE2), a rearrangement product derived from the prostaglandin endoperoxide, PGH2, causes repair-resistant DNA-protein cross-links and cell death (LD50 = 230 nM) in V79 Chinese hamster lung fibroblasts. The half-life for sequestration of LGE2 by covalent binding to cellular nucleophiles is at least an hour for 10 microM LG. This suggests that the in vivo production and distribution of free LGs should be measurable on this time scale. Following removal of the LGE2 and the return of the cultures to normal growth medium, additional DNA protein cross-links continued to form over the ensuing 6-24 h. The results suggest that LG adducts to DNA or protein are not repaired, but react further at sites on protein or DNA in close proximity to the initial adducts, forming cross links in a slow phase of the process. PMID- 8471617 TI - Quantitative multiplex sequence analysis of mutational hot spots. Frequency and specificity of mutations induced by a site-specific ethenocytosine in M13 viral DNA. AB - We describe an assay for determining the frequency and specificity of mutations occurring at hot spots within a population of DNA molecules. The procedure consists of (a) annealing the DNA population with a labeled oligonucleotide designed to prime DNA synthesis at the mutational hot spot; (b) DNA elongation in the presence of a single dideoxynucleoside triphosphate together with 1-3 deoxynucleoside triphosphates, and (c) quantitation of all limit elongation products by high-resolution gel electrophoresis followed by autoradiography and computing densitometry. Derivation of mutational frequency and specificity over a wide range of values is demonstrated for M13 viral DNA mixtures containing defined proportions of wild-type and mutant DNAs, as well as for M13 viral DNA populations obtained by transfection of DNA bearing a defined site-specific ethenocytosine lesion. The assay is shown to yield results similar to those obtained by laborious clone-by-clone sequencing of viral progeny. The method is not affected significantly by several tested variables and appears to be suitable for use as a quantitative assay for sequence microheterogeneity at defined positions within DNA populations. Application of the methodology demonstrates that ethenocytosine, an exocyclic DNA lesion induced by carcinogens such as vinyl chloride and urethane, is a highly efficient mutagenic lesion with a mutational specificity expected for noninstructive lesions. PMID- 8471618 TI - UV irradiation of Escherichia coli modulates mutagenesis at a site-specific ethenocytosine residue on M13 DNA. Evidence for an inducible recA-independent effect. AB - Mutagenic action of chemical and physical mutagens is mediated through DNA damage and subsequent misreplication at sites of unrepaired damage. Most DNA damage is noninstructive in the sense that the causative chemical modification either destroys the template information or renders it inaccessible to the DNA polymerase. Noninstructive adducts possess high genotoxicity because they stop DNA replication. Replication past noninstructive adducts is thought to depend on induced functions in addition to the regular replication machinery. In Escherichia coli, noninstructive DNA damage leads to induction of the SOS regulon, which in turn is thought to provide the inducible functions required for replicative bypass of the lesion. Because of the absence of accessible template instruction, base incorporation opposite noninstructive lesions is inherently error-prone and results in mutagenesis. Ethenocytosine (epsilon C), an exocyclic DNA lesion induced by carcinogens such as vinyl chloride and urethane, is a highly mutagenic, noninstructive lesion on the basis of its template characteristics in vivo and in vitro. However, mutagenesis at epsilon C does not require SOS functions, as evidenced by efficient mutagenesis in recA-deleted E. coli. Even though efficient mutagenesis in recA-deleted cells shows a lack of SOS dependence, the question remains whether SOS induction can modulate mutagenesis opposite epsilon C. To examine the possible contribution of SOS functions to mutagenesis at epsilon C, we constructed an M13 duplex circular DNA molecule containing an epsilon C residue at a unique site. The construct was transfected into nonirradiated or UV-irradiated E. coli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471619 TI - CA runs increase DNA flexibility in the complex of lambda Cro protein with the OR3 site. AB - The alternating pyrimidine-purine elements CA, CAC, and CACA are anisotropically flexible, as deduced from gel circularization assays on point mutations and single-base mismatches in the OR3 site of lambda phage alone and in the specific complex with the Cro protein. These sequences evidently promote DNA bending in the specific binding region of the complex and may also facilitate overwinding in the central nonbinding region. Effects for CACA are exceptionally large and suggest that an alternative DNA structure may occur in this element. PMID- 8471620 TI - Kinetics of Escherichia coli helicase II-catalyzed unwinding of fully duplex and nicked circular DNA. AB - Escherichia coli helicase II (UvrD) protein can initiate unwinding of duplex DNA at blunt ends or nicks, although these reactions require excess protein. We have undertaken kinetic studies of these reactions in order to probe the mechanism of initiation of unwinding. DNA unwinding was monitored directly by using agarose gel electrophoresis and indirectly through the rate of ATP hydrolysis by helicase II in the presence of an ATP-regenerating system. In the presence of fully duplex DNA and excess helicase II, the rate of ATP hydrolysis displays a distinct lag phase before the final steady-state rate of hydrolysis is reached. This reflects the fact that ATP hydrolysis under these conditions results from helicase II binding to the ssDNA products of the unwinding reaction, rather than from an intrinsic duplex DNA-dependent ATPase activity. Unwinding of short blunt-ended duplex DNA (341 and 849 base pairs) occurs in an "all-or-none" reaction, indicating that initiation of unwinding by helicase II is rate-limiting. We propose a minimal mechanism for the initiation of DNA unwinding by helicase II which includes a binding step followed by the rate-limiting formation of an initiation complex, possibly involving protein dimerization, and we have determined the phenomenological kinetic parameters describing this mechanism. Unwinding of a series of DNA substrates containing different initiation sites (e.g., blunt ends, internal nicks, and four-nucleotide 3' vs 5' ssDNA flanking regions) indicates that the rate of initiation is slowest at nicks and, surprisingly, at ends possessing a four-nucleotide 3' ssDNA flanking region. PMID- 8471621 TI - Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes. AB - The interactions between the polyene antibiotic amphotericin B with dipalmitoylphosphatidylcholine were investigated in vesicles (using circular dichroism) and in chloroform solution (using circular dichroism and 1H, 13C, and 31P nuclear magnetic resonance). The results show that amphotericin B readily aggregates in vesicles and that the extent of aggregation depends on the lipid:drug concentration ratio. Introduction of sterol molecules into the membrane hastens the process of aggregation of amphotericin B. In chloroform solutions amphotericin B strongly interacts with phospholipid molecules to form a stoichiometric complex. The results suggest that there are interactions between the conjugated heptene stretch of amphotericin B and the methylene groups of lipid acyl chains, while the sugar moiety interacts with the phosphate head group by the formation of a hydrogen bond. A model is proposed for the lipid amphotericin B complex, in which amphotericin B interacts equally well with the two lipid acyl chains, forming a 1:1 complex. PMID- 8471622 TI - Relationship between molecular conversions of acrosin and the progression of exocytosis in the calcium ionophore-induced acrosome reaction. AB - In this study we used a previously characterized monoclonal antibody to analyze the molecular conversions of acrosin during the acrosomal exocytosis induced by ionophore A23187. Before sperm exposure to the ionophore, most of the sperm acrosin was in the form of proacrosin (55-kDa and 53-kDa forms). Upon exposure to the ionophore, the concentration of proacrosin in sperm samples decreased rapidly and was negatively correlated with the progression of exocytosis. After 1 h of ionophore treatment, proacrosin was quantitatively converted into the two active acrosin forms, alpha-acrosin (49 kDa) and beta-acrosin (36 kDa). However, products of further acrosin conversions were not found after this treatment. As compared with the speed of acrosin activation during sperm contact with the ionophore, the ionophore-induced release of acrosin from the sperm cells into the soluble fraction was apparently delayed, and only the active acrosin forms (49 kDa and 36 kDa) were found in sperm incubation media. External Ca2+ influenced the speed of proacrosin conversion in a concentration-dependent manner. The ionophore-induced activation of proacrosin and acrosome reaction were partially inhibited by trypsin inhibitors. The results suggest that proacrosin activation is an essential step in the mechanism of the acrosomal exocytosis. PMID- 8471623 TI - Thrombin and NaF, but not epinephrine, raise cytosolic free Na+ in human platelets. AB - We have investigated changes in [Na+]i in SBFI-loaded platelets stimulated at 37 degrees C with thrombin, epinephrine, and NaF. Basal [Na+]i was 4.9 +/- 1.3 mM (n = 70). Stimulation of platelets with thrombin (0.1 U/ml) in the presence of 1 mM extracellular Ca2+ rapidly raised [Na+]i by 27.3 +/- 6 mM (n = 16). Part of this increase (approx. 20-30%) is caused by Na+/H+ exchange, the rest is predominantly due to Na+ influx. Epinephrine (20 microM) failed to change [Na+]i both in the absence and presence of fibrinogen. This is in agreement with earlier reports showing that epinephrine also fails to activate Na+/H+ exchange in human platelets. NaF which activates platelets via a direct effect on GTP-binding proteins induced a slow rise in [Na+]i to 9.5 +/- 2.5 mM (n = 4) and 33.0 +/- 3.6 mM (n = 12) at 10 and 20 mM NaF, respectively. This effect was completely blocked by SK&F 96365, a blocker of receptor-mediated Ca2+ entry. Hence, the NaF-induced increase in [Na+]i is exclusively due to the opening of non-selective cation channels. This latter finding agrees with earlier observations which showed that NaF does not induce activation of Na+/H+ exchange in platelets. PMID- 8471624 TI - Calcium and GTP-gamma-S as single effectors of secretion from permeabilized rat mast cells: requirements for ATP. AB - Treatment with metabolic inhibitors and addition of exogenous MgATP exerted different effects on secretion from streptolysin-O-permeabilized mast cells, responding to calcium and GTP-gamma-S as single effectors (i.e., independently of each other). These effects were also strongly dependent on the experimental conditions. Thus cells, triggered by Ca2+ at the time of permeabilization, did not require MgATP, but after metabolic inhibition rapidly became absolutely dependent on its provision, requiring high (> mM) concentrations. AMP-PNP was not effective. After longer treatment with metabolic inhibitors, the absolute dependence on MgATP was also exhibited by cells responding to dual effectors (i.e., Ca2+ and GTP-gamma-S applied together). In contrast, calcium independent secretion due to GTP-gamma-S was more resistant to metabolic inhibition, exhibiting no absolute requirements for MgATP. Once the responsiveness to GTP gamma-S had been lost, it could not be restored by addition of MgATP. MgATP, in fact, inhibited the response of permeabilized cells to GTP-gamma-S. This effect could be mimicked by AMP-PNP. When permeabilized cells were washed before triggering, MgATP (0.1-1 mM concentration range) was no longer inhibitory but stimulatory. These differences between Ca(2+)- and GTP-gamma-S-induced responses indicate that ATP utilization is essential to the calcium, but not to the guanine nucleotide, pathway to secretion. The rate of the response to calcium/MgATP was much slower in the absence than in the presence of GTP-gamma-S. The onset of secretion occurred after an initial delay. This lag phase was abolished by addition of GTP-gamma-S, suggesting that a GTP-binding protein may control a reaction which constitutes a rate-limiting step in the secretory process. PMID- 8471625 TI - Calcium-induced secretion from permeabilized rat mast cells: requirements for guanine nucleotides. AB - Cells used in this work were permeabilized by streptolysin-O and then washed to remove freely soluble components. The secretory responsiveness of these cells to various combinations of calcium, MgATP and guanine nucleotide was characterized and in most respects was found to be similar to that of the metabolically inhibited (unwashed) cells. The content of adenosine and guanine nucleotides, which remain within the permeabilized cells after washing, was estimated as 0.83 and 0.12 mM (extrapolated to intact cells), which constitutes 18 and 25%, respectively, of the total nucleotide content of mast cells. High (> mM) concentrations of MgATP, required for the calcium-induced secretion, were reduced to microM levels by suboptimal concentrations of GTP, which also markedly increased both the rate and extent of the response. Similarly, microM concentrations of MgATP reduced the requirements of the calcium-dependent secretion for GTP. The synergy of the GTP and ATP effects suggests that, together, the two nucleotides can maintain a pool of free GTP, presumably as a result of transphosphorylation from ATP to GDP. Thus, MgATP may work by transphosphorylating the endogenous GDP. However, neither GTP nor GTP-gamma-S were effective as substitutes for MgATP in the calcium-induced secretion, particularly that from metabolically inhibited cells. This indicates that MgATP does not act simply by providing GTP but is needed to maintain a phosphorylated state of the system. The synergistic effects of ATP and GTP were observed only in the presence of calcium. To test whether calcium/MgATP-induced secretion requires an activated G protein, the effects of G-protein inactivators were studied. GDP, deoxy GDP and GDP-beta-S exerted differing degrees of inhibition on secretory responses induced by various combinations of effectors. The response to calcium/MgATP was less sensitive to these inhibitors than that to GTP-gamma-S (with or without calcium). However, all three 'inhibitors' were also capable of stimulating calcium/MgATP-dependent secretion, indicating a transphosphorylation, producing GTP, dGTP and GTP-beta-S. Thus, in the absence of any specific inhibitors for either G proteins or the transphosphorylation reaction, the degree of dependence of the calcium-induced secretion on a G protein remains unclear. PMID- 8471626 TI - Differentiation of human monoblastic leukemia U937 cells induced by inhibitors of myosin light chain kinase and prevention of differentiation by granulocyte macrophage colony-stimulating factor. AB - Inhibitors of protein kinase activities are useful for the study of intracellular signal transduction and some of these inhibitors are reported to induce differentiation of human leukemia cells. We examined effects of granulocyte macrophage colony-stimulating factor (GM-CSF) in combination with several kinase inhibitors on differentiation of human leukemia U937 cells. Nitroblue tetrazolium (NBT)-reducing activity, a typical marker of myelomonocytic differentiation, of U937 cells was induced by genistein and GM-CSF enhanced this activity. GM-CSF also induced the NBT-reducing activity of the cells in combination with 2,5 dihydroxycinnamic acid methyl ester, psi-tectorigenin and staurosporine, although each of them did not induce the activity. Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4 diazepine hydrochloride (ML-7), induced in U937 cells NBT-reduction, and lysozyme and alpha-naphthyl acetate esterase activities. GM-CSF inhibited this differentiation and counteracted the anti-proliferation effect of the kinase inhibitors. These results suggest that some protein kinases are involved in differentiation of U937 cells and the kinases inhibited by ML-9 and ML-7 are associated with signal transduction of GM-CSF. PMID- 8471627 TI - Regulation of eukaryotic translation initiation factor expression during T-cell activation. AB - Primary T-cells are metabolically quiescent, with little DNA, RNA or protein synthesis. Upon mitogenic stimulation the rate of protein synthesis increases 10 fold. We have studied the role of eIF-2 and eIF-4 alpha (eIF-4E) expression in the mechanism of translational activation. During this period, the levels of eIF 2 alpha and eIF-4 alpha mRNA increase some 50-fold. Similar to the increase in ribosomes and mRNA, the number of eIF-2 alpha, eIF-2 beta, and eIF-4 alpha molecules per cell also increase 2-3-fold. This suggests that in addition to an increase in the pool size of translational components, an additional mechanism exists which results in an increased efficiency of factor utilization. We have looked at initiation factor phosphorylation. We find that eIF-2 alpha does not undergo significant changes in its phosphorylation state nor is there a change in the efficiency of eIF-2 utilization. However, there is a rapid increase in the phosphorylation state of eIF-4 alpha which correlates with the rapid increase in translational activity. It thus appears there are 2 distinct components responsible for the translational activation of quiescent T-cells during mitogenic stimulation. The first is the phosphorylation of eIF-4 alpha, with a concomitant increase in the efficiency of eIF-4 alpha utilization. The second is an increase in the pool sizes of eIF-2 and eIF-4 alpha. PMID- 8471628 TI - Production and regulation of gelatinase B by human T-cells. AB - Here we describe for the first time the production of gelatinase B (MMP 9; 92-kDa type IV collagenase) by human peripheral blood T-lymphocytes. Expression of this enzyme was found to be dependent on the activation status of these T-cells and to be regulated by Interleukin-2. PMID- 8471629 TI - Protein kinase C isotypes and signal-transduction in human neutrophils: selective substrate specificity of calcium-dependent beta-PKC and novel calcium-independent nPKC. AB - Neutrophils possess at least two phospholipid-dependent forms of protein kinase C, a classical Ca/PS/DG-dependent beta-isotype of protein kinase C and a Ca independent but PS/DG-dependent novel protein kinase C (nPKC) which we now demonstrate to have different substrate specificities. Activation of human neutrophils triggers assembly of an NADPH oxidase in the membrane and generation of O2-. A role for the major Ca-dependent isotype beta-PKC in neutrophils is proposed in stimulus-induced phosphorylation and association of a cytosolic 47 kDa protein (p47-phox) with the membrane NADPH oxidase. In this study we demonstrate that purified beta-PKC and nPKC have very different substrate specificities; beta-PKC but not nPKC phosphorylated both endogenous and recombinant p47-phox. In addition, beta-PKC but not nPKC phosphorylated [ser25]PKC(19-31), the substrate peptide based on a sequence in the Ca-dependent alpha, beta and gamma-isotypes. Pseudosubstrate(19-36), derived from the C terminus of Ca-dependent PKC isotypes, inhibited beta-PKC but not nPKC activity using either Histone IIIS or peptide(19-31) as substrate. Pseudosubstrate(19-36) also inhibited beta-PKC catalyzed phosphorylation of endogenous and recombinant p47-phox. Pseudosubstrate(19-36) also inhibited the O2- generation triggered by GTP gamma S in electroporated neutrophils by 50%. 32P-Labelled neutrophils electroporated in the presence of GTP gamma S showed phosphorylation of multiple cytosolic proteins including a 47 kDa band, and phosphorylation of membrane associated 34 kDa, 47 kDa and 54 kDa proteins. Pseudosubstrate(19-36) inhibited phosphorylation of p47-phox in the membrane but not in the cytosol. These findings suggest translocatable, Ca-dependent isotypes of PKC such as beta-PKC may play a role in the phosphorylation of membrane associated p47-phox and the assembly or maintenance of an active NADPH oxidase. PMID- 8471630 TI - Establishment of an enzyme immunoassay system for gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF). AB - A two-site enzyme immunoassay for gliostatin (GLS)/platelet-derived endothelial cell growth factor (PD-ECGF) has been developed. The detection limit of gliostatin/PD-ECGF was 30 pg/well, and the optimal assay range was 0.1 to ng/well. This assay system enabled us to confirm the immunochemical identity of both factors and to detect immunoreactive gliostatin/PD-ECGF (IR-GLS/PD-ECGF) in human biological body fluids. The age-related analysis from newborn to 69 years revealed that the serum IR-GLS/PD-ECGF level was high in infants younger than 1 year old (1.8 ng/ml) and in the 20-year-old age group (1.8 ng/ml), and highest in the umbilical cord blood (2.1 ng/ml). Curiously high concentrations were detected in saliva with a significant sex difference (11.3 ng/ml for males and 48.7 ng/ml for females), and in synovial fluids (3.7 ng/ml). A number of human tumor cells, gastric cancer cells, MKN-74, neuroblastoma cells, GOTO, as well as epidermoid carcinoma cells, A431, were found to produce a significant amount of IR-GLS/PD ECGF (0.2 to 21.8 ng/mg protein), and some of them secreted the IR-GLS/PD-ECGF in the conditioned medium (approximately 0.5 ng/ml). The enzyme immunoassay system is sufficiently sensitive for the basic and clinical study of gliostatin/PD-ECGF in human body fluids, tissues and organs. PMID- 8471631 TI - The mechanism of inhibition of alkylamines on the mast-cell peptidergic pathway. AB - GTP-binding proteins are known to play an important role in controlling mast-cell exocytosis and are described as the primary targets of peptidic mast-cell histamine releasers. The mechanism of inhibition of the mast-cell peptidergic pathway by alkylamines, which are selective inhibitors of this pathway, was investigated using intact or permeabilized rat peritoneal mast cells. Histamine release induced by GTP gamma S and by mastoparan (a venom peptide activating G proteins) was inhibited by pretreating mast cells with 0.1 to 3 micrograms/ml of a mixture of benzalkonium chloride containing in majority a twelve-carbon-atom aliphatic chain (BAC(C approximately 12)). Pure benzalkonium chloride, with a fourteen-carbon-atom aliphatic chain (BAC (C14)), at 5 to 10 microM also inhibited histamine release induced by GTP gamma S and mastoparan. The dose response curve of mastoparan-induced histamine release from intact mast cells was shifted to the right by various concentrations of BAC (C14). Similar results were obtained with another alkylamine differing from BAC (C14) by the absence of the benzene ring, tetradecyltrimethylammonium bromide, TAB (C14). This illustrates that the presence of the phenyl radical is not required for the inhibitory effect of benzalkonium chloride. BAC (C approximately 12) and BAC (C14) inhibited the generation of inositol polyphosphates induced by GTP gamma S. BAC (C approximately 12) and TAB (C14) inhibited the mastoparan-stimulated GTPase activity from mast-cell Gi-like proteins. These results suggest that alkylamines exert selectively their inhibitory effect via an interaction with mast-cell Gi like proteins coupled to phospholipase C, i.e., at an early stage in the stimulus secretion coupling process. PMID- 8471632 TI - Adenylyl cyclase in lung from hypersensitive guinea pig displays increased responsiveness to guanine nucleotides and isoprenaline: the role of the G proteins Gs and Gi. AB - Basal adenylyl cyclase activity in lung membranes isolated from hypersensitive guinea pigs was increased and more sensitive to stimulation by isoprenaline, GTP and GppNHp when compared to adenylyl cyclase in lung membranes isolated from normal healthy guinea pigs. Maximal forskolin-stimulated adenylyl cyclase activity was unaltered. There was no change in the immunological quantitative amounts of either alpha subunits of the G proteins GiII and Gs (G(o), GiI and GiIII were not present). Maximal pertussis-toxin- and cholera-toxin-catalyzed ADP ribosylation of Gi alpha and Gs alpha respectively were not significantly altered. The addition of purified protein kinase C to isolated lung membranes resulted in the phosphorylation of the alpha subunit of Gs (stoichiometry was 0.53 mol of 32P incorporated/mol of Gs alpha). Addition of protein kinase C to lung membranes isolated from hypersensitive guinea pigs was equally effective at catalysing the phosphorylation of the alpha subunit of Gs. GppNHp-stimulated and basal adenylyl cyclase activity was also enhanced in isolated tracheal smooth muscle membranes from hypersensitive guinea pigs. These results suggest that hypersensitive reactions are associated with the improved coupling of the stimulatory G protein (Gs) with adenylyl cyclase. PMID- 8471633 TI - Primary sites of actions of staurosporine and H-7 in the cascade of insulin action to glucose transport in rat adipocytes. AB - The insulin-stimulated glucose transporter in rat adipocytes was inhibited by two protein kinase inhibitors, staurosporine (SSP) and H-7 (1-(5 isoquinolinylsulfonyl)-2-methylpiperazine). However, whereas SSP (10 microM) blocked the insulin-dependent translocation of glucose transporter, H-7 (3 mM) did not. The latter inhibited glucose transporter activity not only in cells, but also in reconstituted liposomes. On the other hand, SSP blocked both the action of insulin and the insulinomimetic action of GTP gamma S (Guanosine 5'-O-(3 thiotriphosphate)). GTP gamma S had distinct effects on the glucose transport and cAMP phosphodiesterase (PDE) activities. It is suggest that H-7 may inhibit glucose transport activity per se; a SSP sensitive protein kinases (protein kinase C isoforms?) may be involved in cascade of the insulin action on glucose transporter as modulated by GTP gamma S; and glucose transport and PDE activities may be regulated by distinct GTP gamma S-sensitive factors. PMID- 8471634 TI - Differential effects of activation of protein kinase C and cyclic-AMP-dependent protein kinase on sodium-dependent phosphate uptake in NIH 3T3 cells. AB - Activation of protein kinase C (PKC) by phorbol ester (PMA), or by diacylglycerol analogue (OAG) treatment of NIH 3T3 cells resulted in the rapid (within 2-5 min) stimulation (approx. 2-fold) of sodium-dependent phosphate (Pi) transport. Conversely, preincubation of these cells with forskolin and cholera toxin, or incubation with 8-bromo-cAMP, to activate cAMP-dependent protein kinase (PKA), resulted in a decrease in Na+/Pi transport. Activation of either PKC or PKA did not change the Vmax of Pi uptake. However, activation of PKC did result in an increase, while activation of PKA caused a decrease, in the affinity for Pi. These results indicate that there is differential regulation of Na+/Pi uptake in NIH 3T3 cells by activators of PKC (stimulated) and PKA (inhibited) as a consequence of changes in the affinity of the transporter for Pi. PMID- 8471635 TI - [Analysis of the conformational mobility of DNA in transcriptionally-active chromatin]. AB - An attempt is made to estimate the degree of conformational flexibility of DNA in different fractions of nucleosomes of transcriptionally active chromatin of higher eukaryotes, and in yeast nucleosomes as well. We have used the circular dichroism method to estimate conformational changes in DNA induced by temperature shift. The DNA conformational potential was shown to be approximately the same in all the fractions of nucleosomes under study. PMID- 8471636 TI - [From disorder to order using the example of the function of phage T4 baseplate]. AB - The structure of key elements of T4 baseplate distal part was investigated by electron microscopy and image processing. The functional aspects of interaction of distal part structures in cell infection process were discussed. According to the results obtained earlier the baseplate functioning was suggested to be like a synchronization process of the complex protein structure caused by variation of external factors. PMID- 8471637 TI - [Cleavage time for a hydrogen bond under a load]. AB - Statistics of the hydrogen bond formation and break in a bundle of actin and myosin filaments realizing the attractive force in the sarcomere of a muscle is studied. Purely mechanical problem of the attractive-force formation and motion of myosin heads and action globules under their action is supplemented by accounting for the irreversible processes: 1. Thermal de-excitation of the latter in the chain of hydrogen bond during the elementary act of the ATP energy use resulting in fixing the extended actin filament. 2. Break of the hydrogen bonds, realizing this fixing, due to thermal fluctuations for the time tau. The average life-time turns out to be the order of time necessary for the movement of z membrane sarcomere for the value of action filament extension delta 1, which is necessary for the process of muscle contraction to be continued. PMID- 8471638 TI - [Parametric resonance as a possible mechanism of action of superlow concentrations of biologically active substances at the cellular and subcellular levels]. AB - At extra-low concentrations of biologically active substances (BAS) the limiting stage of processes determining their action at cell and sub-sell levels is BAS diffusion to the cell surface. According to proposed parametric resonance model the BAS activity extreme values are to be observed when the reciprocal values of collision frequency between BAS molecules and cell surface coincide (by order of magnitude) with the characteristic times of conformational relaxation of certain macromolecular structures responsible of the studied process. The calculation results do not contradict the experimental data. PMID- 8471639 TI - [Formation of stabile cupola-like lipid bilayer membranes with a mobile plateau Gibbs boundary]. AB - Stable bilayer lipid membrane with mobile Platear-Gibbs border have been formed. The predominant condition of the formation is the presence of lipid coverage on the teflon surface near the hole. The formation process includes transformation of the initial planar lipid bilayer into cupola-shaped one by bowing of the lipid bilayer due to hydrostatic pressure, movement of the PGb along the teflon surface. The bilayer area estimated by electric capacitance increases from 0.1 x 10(-8) F to 21 x 10(-8) F. Electric conductance of the lipid bilayer has not changed except for the phase transition and membrane collapse. The electric capacitance of the BLM formed from hydrogenated egg lecithin was changed by cooling between 60 degrees and 40 degrees C with the maximum at about phase transition range. The individual membrane sustains several scannings of the temperature without disruption which is an evidence of the stability of the cupola-shaped membranes. PMID- 8471640 TI - [Uterotonic effect of oxytocin and transport of Ca2+ through the myometrial sarcolemma]. AB - Effect of oxytocin on contractile activity, passive and Mg2+, ATP-dependent Ca2+ transport through myocyte plasmic membrane was studied in the experiments carried out on intact samples of the uterus smooth muscle and fraction of myometrium sarcolemma vesicules. It was shown that at short-term (30 s) application of oxytocin (2.10(-7) M) powerful prolonged contractile reaction of myometrium bands was observed. After the chelating of Ca2+ in the washing medium by means of EGTA (2mM) or while introducing into it blockers of electrically controlled calcium channels the bands responded to oxytocin application with a single physical contraction. High concentrations of peptide hormone (10(-6) M) introduced into the preincubation medium of the smooth muscle bands before the isolation of the membrane fraction or directly into the incubation medium produced no effect on passive liberation of Ca2+ vesicules from the sarcolemma vesicules. At the same time preincubation of the bands in the solution containing smaller concentration of octapeptide (10(-7) M) decreased the initial velocity of Mg2+, ATP-dependent Ca2+ transport in the vesicules by 30% on the average. Possible mechanisms of oxytocin effects on intracellular homeostasis of Ca2+ in the myometrium, on the contractile activity of the uterus are discussed. PMID- 8471641 TI - [Postural adjustments to voluntary movements. Electrical activity of muscles and biomechanics of the human body in an upright position]. AB - Involuntary movements of the pelvis and legs which accompany voluntary arm flexion and correct the orthograde posture start in most trials in normal subjects simultaneously with the voluntary arm movement or later was demonstrated. At the same time bursts of legs and trunk muscles activity anticipate the burst of m.deltoideus activity. In this situation the electromechanical delay (EMD) of m.deltoideus is significantly shorter (13-18 ms) than EMD of legs and trunk muscles (70-80 ms). Perhaps more long EMD of legs and trunk muscles in orthograde posture "impels" anticipation of its activity for economic control of the body position in initial period of a fast voluntary movement. PMID- 8471642 TI - [Experimental evidence in the use of the new tracking role of imino acids in the thermodynamics of collagen type proteins]. PMID- 8471643 TI - [Ionic pairs in Bacillus intermedius 7P ribonuclease]. AB - On the basis of X-ray determined coordinates specified with computer graphics and new data on amino acids sequence in the structure of Bacillus intermedius 7P ribonuclease there were analysed potentially charged residues and found ionic pairs binding independently denaturing regions-energetic domains. Five clusters of charged amino acids were found in the protein structure and several ionic bonds between the energetic domains were discovered: Asp7, Asp11-Arg109 and Lys26 Asp53,Glu72. Breaking of the latter makes their heat denaturation independent. Local surrounding of the ionic bonds is characterized and their role in the structure and cooperative properties of the globule is discussed. PMID- 8471644 TI - [Molten globule unfolding by strong denaturing agents occurs by the "all or nothing" principle]. AB - The equilibrium Gu-HCl-induced denaturation of bovine carbonic anhydrase B and beta-lactamase from Staphylococcus aureus was studied at 4 degrees C by the multiparametric approach. With the use of fast protein size-exclusion chromatography (FPLC) it has been shown that in the region of the molten globule random coil transition the distribution function of the protein molecules on size is bimodal, i.e. the protein molecules (which are already denatured) can only in one of two conformational states. Consequently the unfolding of the molten globule can be of "all-or-none" character. This means that a protein molecule can be at least in three discrete states: the native, the molten globule and unfolded. PMID- 8471645 TI - [The state of unfolded globules of protein molecules is more quickly becoming a rule, rather than an exception]. AB - A review of experimental data concerning physical properties of globular protein at mild denatured conditions shows that at the present time about 20th proteins were obtained in the "molten globule" state at mild denatured conditions (acid or basic pH, high temperature or moderate concentrations of guanidine hydrochloride or urea). This state is nearly as compact as the native state and has a well pronounced secondary structure but has no rigid tertiary structure. A possible role of the molten globule state in the processes of formation and of degradation of globular proteins are discussed. PMID- 8471646 TI - [Artificial proteins with a given spatial structure and biological activity]. AB - Biologically active fragment 131-138 of human interferon alpha 2 carrying blast transforming activity of the protein was attached to the N-terminus of the de novo protein albebetin with predetermined tertiary structure by means of genetic engineering. The chimeric protein was expressed in a wheat germ cell-free translation system and tested for compactness, stability and biological activity. According to the tests used albebetin with interferon fragment has a compact and relatively stable structure. It binds murine thymocyte receptor with high affinity and activates efficiently thymocyte blast transformation at a concentration of 10(-11) M. PMID- 8471647 TI - [Mechanisms of death of free radical states in proteins]. AB - Mechanism of the death of free radicals formed under the effect of different destructing factors in proteins without a prosthetic group is considered. The death of macroradicals in proteins is suggested to be due to a recombination of free radical states of aromatic amino acid residues and atom hydrogen braking away as a result of transformation of the middle radicals -NH-C alpha R-CO- from the nearest NH-group. Possible way of middle radicals transformation is proposed which leads to the breakage of hydrogen. The mechanism of macroradicals death considered explains basic experimental results obtained in this field. PMID- 8471648 TI - [Self-similarity in the structure of DNA: why are introns needed?]. AB - Consequences of the hypothesis are analyzed that native spatial structure of DNA is the so-called crumpled globule, which is statistically free of knots. Since crumpled globule is self-similar fractal object in space, fixation of more or less unique chain fold, that is the case for eukaryotes, requires some self similarity of the sequence. On this basis we explain quantitatively long-range power-law correlations in intron containing genes which have been discovered recently, predict some more detailed properties of correlations, which partly convinced already in experiment, and formulate a few more general hypotheses on the statistical properties of presently unassigned parts of DNA, on the role of intron as the instrument of fixation of DNA spatial structure and on the possible way of creation of such an apparatus in the evolution. PMID- 8471649 TI - [An experimental model of continuous biliary and vascular access in the free rat: a study of the changes in biliary function under the influence of the parenteral administration of amino acids]. AB - Total parenteral nutrition is associated with different hepatic alterations such as cholestasis, steatosis or cholelithiasis. To study such alterations anaesthetised rats, in which the enterohepatic circulation of bile acids is interrupted, have been widely used. A model of free moving rat with venous and biliary catheterization has been developed in this work. This overcomes the interferences induced by anaesthesia as well the alterations in hydrostatic pressure or restraint-induced stress present in other models. The use of our animal model has confirmed previous data from anesthetised rats indicating that parenteral solutions of amino acids induce a cholestasis effect, with decreases in bile flow but not significant change in bile acid secretion. PMID- 8471650 TI - [A computer program for assessing nutritional status and diet preparation]. AB - This computer program has been written in a BASIC language and designed to assess the nutritional status by means of anthropometrical, immunological and clinical data. Additionally, it is useful for the design and elaboration of personalized diets. The use of this program will allow to work with a great amount of nutritional information, besides, it will outstandingly reduce work time and increase accuracy to diagnose specific nutritional problems. The data base of this program has been made on the basis of current nutritional information and it can be easily updated when necessary. PMID- 8471651 TI - [The fructosamine monitoring of the effect on glycemic control of hypocaloric parenteral nutritional support with glycerol]. AB - The objective of this paper is to examine the usefulness of plasmatic fructosamine finding as an indicator of glycemic control in patients with hypocaloric parenteral nutrition with glycerol. Thirty abdominal surgery patients were studied. None displayed malnutrition, diabetes mellitus, hepatopathy, nephropathy or hyperlipemia in the preoperative stage or during the five days of postoperative recovery they were administered hypocaloric parenteral nutrition with glycerol. Their plasma levels of glucose, fructosamine, triglycerides, albumin and total proteins were found in the preoperative stage and on the first and fourth day of postoperative recovery. Following surgery, findings showed an increase in triglycerides and a decrease in the protein compartment, while glycemia levels remained steady. Furthermore there was a positive correlation between the figures for glycemia and later fructosamine figures. The conclusion was that providing hypocaloric nutrition with glycerol does not increase fructosamine levels. This confirmed prior observations on the slightness of its effect on hydrocarbonic metabolisms. PMID- 8471653 TI - [Standard formulas of parenteral nutrition. A study of their use in a general hospital]. AB - The goal of the study was to evaluate the use of parenteral nutrition formulas with standardized g. of nitrogen, carbohydrates and lipids, and to analyze whether the nutritional requirements of the patients treated in our hospital were covered by said formulas or whether it was necessary to change and/or standardize a new formula. To do so, a review was made of 5.646 parental nutrition mixtures prepared in the Pharmacy Service and patterned by the Nutrition Service from April, 1991, to May, 1992, for 308 adult patients. The distribution of the mixtures by services, diagnoses and the frequency of the different standard formulas were studied, comparing standard formula frequency with that of non standard formulas. Findings showed that 41.9% of nutrition mixtures were patterned in surgery, and the most common diagnosis, cancer, appeared in 24%. Of the mixtures, 67.6% were preestablished formulas, and 32.4% were non-standard formulas. The order of frequency among standard formulas was: basic standard formulas, stress formulas, initial formulas, peripheral formulas, hemodialysis formulas and low-volume formulas. All covered the nutritional needs of a large share of the patients for the different pathologies in which they were indicated. Nevertheless the question of designing a new formula to cover a greater number of situations was raised. Protocolization should take place rationally, to meet the hospital's most frequent pathologies, and effectiveness should be evaluated after tracking and checking each patient. PMID- 8471652 TI - [The effect of the administration of an amino acid solution enriched with branched-chain amino acids on the nutritional assessment of patients with stress who require total parenteral nutrition]. AB - The effects of two solutions of amino acids (AA) were compared in the nutritional assessment of stressed patients requiring total parenteral nutrition (TPN) by finding anthropometric, biochemical and immune parameters on day 0 and day 8. In addition, calculations were made to find the nutritional prognosis index, stress index nitrogenated balance (NB) and net protein use (NPU). A double-blind prospective study was run in which 35 patients with moderate to high stress were divided at random into two groups to receive, for seven days, TPN that was both isonitrogenated (1.56 g/Kg/day of AA) and isocaloric (115.6 +/- 13.6 non-protein Kcal/g. nitrogen), 37% as lipids (LCT), differing only in the AA solution used, one being 15.6% and the other, 45% BCAA. Twenty-eight patients finished the study, 14 in each group. No significant differences were found between the groups in the parameters under study; however, the patients who received the 45% BCAA solution obtained superior development of the parameters evaluating nutritional status and an increase in their NB (p = 0.0213) and NPU (p = 0.0497). Total lymphocytes increased significantly in both groups. Disturbances in hepatic enzymes and alkaline phosphatase (AF) were higher than in the standard group. Gamma glutamyl transferase (GGT) increased in group I (p = 0.0168), while in group II there were increases of GGT (p < or = 0.05), glutamic pyruvic transaminase (GPT) (p < or = 0.025) and AF (p = 0.0213). In the standard group, plasma urea increased (p = 0.0117), and the creatine/size ratio decreased (p = 0.0094). Anthropometric measurements were not valid in this study. The results do not allow the conclusion to be drawn that the 45% BCAA solution is the most effective, but it does make clear that its use is suitable in patients with moderate and high levels of stress, changing to standard AA solutions when the patients improve. PMID- 8471654 TI - [A prospective randomized study of the usefulness of weighted versus unweighted feeding tubes. A comparison of the transpyloric passage capacity, duration time and the signs of intolerance for enteral nutrition]. AB - Weighted feeding tubes for parenteral nutrition were designed to facilitate duodenal intubation and to reduce the risk of aspiration into the bronchi. The goal of the study was to compare the effectiveness of two types of tubes, weighted and unweighted, with regard to their ability to pass the pylorus in 24 hours' time, the time they remained, their involuntary detubation percentages, and the appearance of signs of digestive intolerance during enteral nutrition. Only patients who preserved some level of consciousness were included. Thirty eight were fitted with weighted tubes, and 32 with unweighted tubes. Twenty-four feeding tubes reached the duodenum during the first day. The average time the tubes remained after insertion was 10.2 +/- 1.1 (range of 1-51) days. In 20 patients, the tube left the body unnoticed, and 15 displayed signs of intolerance to enteral nutrition, though it had to be suspended in the case of only 5. Weighted feeding tubes showed greater effectiveness in their duodenal intubation rate (47% versus 19%, p = 0.0058), the time they remained in the body (12.2 +/- 1.7 versus 7.9 +/- 1.1 days; p = 0.037) and their percentage of involuntary detubation (6 weighted tubes and 14 unweighted tubes, p = 0.009). There were no differences between the two tube types with regard to the appearance of signs of digestive intolerance. The weighted tubes that reached the duodenum (n = 18) were those which remained for the longest periods; 73% of them remained for over 8 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471656 TI - Hypoplastic myelodysplastic syndrome: incidence, morphology, cytogenetics, and prognosis. AB - The present study, based upon the retrospective evaluation of 352 patients with primary myelodysplastic syndrome (pMDS), revealed hypoplastic MDS in 42 patients (11.9%). Median age is similar in hypo- and normo-/hypercellular MDS (72.6 versus 70.7 versus 72.4 years). Hypoplastic MDS occurred significantly more often in women compared with normo- and hypercellular MDS. Sequential biopsies were performed in 14 patients, showing a persistence of hypoplasia over a period of up to 43 months. The proportion of patients showing mesenchymal reaction, especially an increase of mast cells, was significantly higher in hypoplastic MDS, whereas dysplastic features of hematopoiesis occurred less frequently and were of lower grade in comparison to normo-/hyperplastic MDS. Among the subgroup with hypoplastic bone marrow, the classification according to FAB criteria revealed 28 patients with RA (66.7%), three with RARS (7.1%), and eight with RAEB (19.0%), as well as one patient each with RAEB-T and CMMol (2.4% each), and one case which had to be reckoned among the category of unclassifiable MDS (2.4%). Median survival was 21.8 months for hypoplastic MDS, 26.9 months for normoplastic MDS, and 14.2 months for hyperplastic MDS. During follow-up, 14 patients (33%) with hypoplastic MDS developed acute nonlymphatic leukemia. Although not a constant finding, karyotype abnormalities involving particularly chromosome 7 seem to be associated with hypoplastic MDS. The results confirm the existence of a hypoplastic variant of MDS which seems to more frequently affect female patients, and which requires bone marrow biopsy for its accurate diagnosis. PMID- 8471655 TI - Biology and treatment of myelodysplastic syndromes--developments in the past decade. PMID- 8471657 TI - Analysis of lymphocyte subsets in patients with aplastic anemia before and during immunosuppressive therapy. AB - To define the contribution of T-lymphocyte subsets in the development of aplastic anemia (AA), T-cell subpopulations including alpha beta T cells, gamma delta T cells, and delta TCS1-positive gamma delta T cells, were analyzed by cytophotometry in the peripheral blood (PB) and bone marrow (BM) of patients with AA before and after 6 weeks of therapy with anti-lymphocyte globulin (ALG), methylprednisolone, and cyclosporin A (CSA). In nine patients with AA a significant decrease of PB- and BM-derived T cells was observed after 6 weeks of therapy as compared with normal controls. At diagnosis, the CD4/CD8 ratio in PB and BM of the patients did not differ from the ratio in the control population; however, a reversed ratio (< 1) was present in PB as well as in BM after weeks of therapy. Interestingly, lymphocytes expressing the gamma delta T-cell receptor (TCR tau delta) were significantly decreased both before (PB 1.2 +/- 0.1%; BM 0.8 +/- 0.1%) and after 6 weeks of therapy (PB 0.7 +/- 0.1%; BM 0.7 +/- 0.1%) as compared with healthy controls (PB 2.4 +/- 0.2%; BM 2.3 +/- 0.2%). However, the proportion of the gamma delta-T-cell subpopulation expressing the delta TCS1 phenotype was markedly increased before (PB 42 +/- 3.5%; BM 31 +/- 3%) and especially after 42 days of therapy (PB 77 +/- 12%; BM 45 +/- 2%) as compared with that in normal subjects (PB 19 +/- 2%; BM 9.7 +/- 0.8%). At present, follow up is under evaluation to correlate these findings with hematological response. The pathophysiological significance of the observed alterations within the T-cell subsets and especially the gamma delta T-cell populations will require further functional analyses, in particular since delta TCS1-positive gamma delta T cells exhibit autoimmunological capacity. PMID- 8471658 TI - Phase-II study of treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine. AB - Twenty-five consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12 h, days 1-6) and AMSA (120 mg/m2 i.v., days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h, days 1-4 and AMSA 120 mg/m2 i.v., day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), ten after 1 cycle of induction and two after 2 cycles; 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. Nine patients remained refractory (36%) and four died during hypoplasia (16%). Median DFS of the 12 responders was 2.9 months, median survival from time of CR 8.9 months. Median overall survival of responders and nonresponders was 6 months from time of resistance. Survival advantage of responding patients (n = 12) as compared with nonresponders (n = 13) was 10.7 vs. 3.2 months (p = 0.002). Toxicity of chemotherapy was acceptable: one patient experienced pulmonary edema due to ara C; two patients developed life-threatening systemic fungal infections, one of whom died while in CR. PMID- 8471659 TI - IEVM chemotherapy with rhGM-CSF support for aggressive non-Hodgkin's lymphomas: a pilot study. AB - Modern combination chemotherapy cures about one third of patients with non Hodgkin's lymphomas (NHL) [3]. Attempts to increase this proportion by more intensive chemotherapeutic regimens have failed so far in randomized trials [4, 5]. Dose intensity has been reported to be important for cure [8]--a factor which can be enhanced by hematopoietic growth factors--but addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to intensive chemotherapy did not improve response on survival in a controlled study published recently [10]. Therefore, we tried to design a regimen which might be more appropriate for combination with growth factors, using pulse chemotherapy rather than continuous treatment and employing drugs of low stem-cell toxicity. Ifosfamide (Ifo) appeared to be ideal because it is effective even in some resistant cases [1] and might act synergistically with anthracyclines by reducing intracellular glutathione levels [9]. Epirubicin (Epi) was favored because of its low hemato- and cardiotoxicity [2]. These drugs, together with etoposide (VP-16) had been found to be very effective in relapsed cases [7]. Methotrexate (Mtx) was added because it penetrates the spinal fluid. Moreover, we chose granulocyte/macrophage colony-stimulating factor (rhGM-CSF) as an adjunct cytokine because this not only enhances neutrophil regeneration [6] but might also have antitumor effects, as suggested by an uncontrolled study in sarcomas [11]. This report summarizes our experiences regarding feasibility, toxicity, and responses with this new regimen obtained in a pilot study. PMID- 8471660 TI - Multiple myeloma: effect of daily dichloromethylene bisphosphonate on skeletal complications. AB - In 1989, a prospective randomized multicenter study was initiated in order to determine the safety and efficacy of oral clodronate in myeloma patients. The primary objective of this long-term trial is to evaluate whether supportive clodronate is able to prevent or retard the progression of bone disease and reduce the occurrence of characteristic complications: pain, pathologic fractures, and hypercalcemia. We now report first results as an interim analysis, including data obtained from 26 patients (total number of Tubingen patients n = 36) who entered the study at the Medizinische Universitatsklinik Tubingen. Patients were randomized to receive either chemotherapy alone (melphalan 15 mg/m2 i.v. on day 1 and prednisolone 60 mg/m2 orally on days 1-4 every 4 weeks (control group) or in combination with 1600 mg clodronate/day orally as a single dose for a period of at least 1 year. Repeated radiologic examinations in addition to hematologic and biochemical analysis were performed in order to evaluate the skeletal status with respect to lytic bone lesions and osteoporosis and the course of serum M protein and light chain excretion into urine. Clodronate treatment resulted in a significant decrease of serum calcium concentrations and of biochemical indices for bone resorption. No clodronate-related toxicity or hypocalcemia was observed. In patients treated with chemotherapy alone, this effect was less marked and discontinuous. Clodronate-treated patients developed fewer progressive bone lesions (significant for lytic, not for osteoporotic lesions). No hypercalcemic episodes occurred in the clodronate-treated patients, but there were six episodes in the control group. Whereas the number of vertebral fractures was evidently less is clodronate-treated patients, three of those patients suffered from multiple fractures of long bones and ribs. All together, 12 pathologic fractures occurred in five clodronate-treated patients, whereas in the control group 23 pathologic fractures occurred in the same number of patients during the whole observation period. The final analysis of all multicenter included patients should clarify these findings. There was a significant finding that clodronate proved to have an analgesic effect. PMID- 8471661 TI - Acute agranulocytosis after prolonged high-dose usage of intravenous dipyrone--a different mechanism of dipyrone toxicity? AB - Two seriously injured trauma patients presenting with intense and progressive neutropenia are described. Bone marrow examination in both cases showed virtually absent granulopoiesis but normal erythropoiesis and megakaryopoiesis, allowing the diagnosis of acute agranulocytosis. Discontinuation of only one drug (dipyrone) with no further treatment was required for normalization of blood parameters. The association of dipyrone with neutropenia is still debatable. The recent medical literature on dipyrone generation of agranulocytosis is reviewed. PMID- 8471662 TI - Possible selective effects of interferon alpha-2b on a malignant clone in a case of polycythemia vera. AB - A patient with polycythemia vera associated with chromosomal translocation (6;8) (q27;p11) and IgA monoclonal gammopathy was treated with interferon alpha-2b. Interferon alpha-2b induced good hematological control and reduced only IgA levels, but not IgG and IgM levels. In addition, cytogenetic improvement was obtained, the abnormal cells with chromosomal translocation declining from 100% to 50%. Interferon alpha may have selective effects on a malignant clone in polycythemia vera. PMID- 8471663 TI - Flow-cytometric enumeration of reticulocytes. PMID- 8471664 TI - [Diadenosine oligophosphates: metabolic pathways and role in regulating the functional activity of cells]. AB - Recent data on the content and biological role of diadenosine oligophosphates in procaryotic and eucaryotic cells, animal tissues and organs are reviewed. The specific ways of their synthesis and dissociation are presented. The role of diadenosine oligophosphates in regulation of cell proliferation and as protectors from cells damage with cytotoxic agents in discussed. The perspectives uses of diadenosine oligophosphates in medicine have been examined. The role of a universal diadenosine oligophosphates system in regulation of cell biological activity is postulated. PMID- 8471665 TI - [Study of phage T7 DNA-dependent RNA-polymerase using GTP analogs. Affinity modification and study of interaction with matrices using fluorescent markers]. AB - Interactions of the bacteriophage T7 DNA-dependent RNA polymerase with three GTP analogs have been studied. All of the three analogs tested contained substituted naphthalenesulphamide groups and were shown to be under appropriate conditions irreversible covalent inhibitors of the enzyme, the modified enzyme possessing fluorescent properties. One of these analogs contained the reactive 2-bromoethyl phosphonate group and was shown to cause the loss of the enzyme affinity for polynucleotide templates. The other two modifiers which contained the azide reactive group did not alter the enzyme-template affinity, the polynucleotide binding leading to a notable increase of the enzyme fluorescence intensity. The latter two modifiers are supposed to be convenient for fluorescent labelling of the active site of RNA polymerase for enzyme-template binding studies. PMID- 8471666 TI - [Status of cell membrane enzymes in hypoxia and the protective effect of pyrazidole]. AB - The influence of hypobaric hypoxia simulating the altitude of 9000 m above the sea level during 3 hours on the stability of erythrocyte, lysosomal, and mitochondrial membranes, has been studied. The increase in extra erythrocyte hemoglobin and free iron concentrations and the total peroxidase activity in blood plasma testify to increased permeability of the erythrocyte membrane. An increase in the free activity of acid peptide hydrolases in the soluble fraction and their activity decrease in the lysosomal membrane. The mitochondrial monoamine oxidase activity in the soluble fraction of the brain is suggestive of structural damages to the mitochondrial membrane. Preliminary administration of pyrasidol prior to hypoxia has a stabilizing effect on all types of membrane structures. PMID- 8471667 TI - [mRNA with an extended Shine-Dalgarno sequence is translated independently of ribosomal protein S1]. AB - The role of the ribosomal protein S1 in translation of a mRNA containing an extended Shine-Dalgarno sequence has been investigated. Using the toe printing technique, the formation of a ternary initiation complex with both S1-depleted 30S subunits and subunits treated with anti-S1 antibodies and mini-mRNA containing an lambda-cro-mRNA translational initiation region with a very long (9 nucleotides) Shine-Dalgarno sequence, has been demonstrated. It is concluded that initiation of translation on mRNA with extended SD-sequence is S1-independent. By means of an E. coli cell-free system of translation (S-100 extract), the translation of mini-cro-mRNA by S1-depleted ribosomes has been shown. In contrast with mini-cro-mRNA, the 30S subunits without protein S1 are inactive both in the ternary initiation complex formation and in cell-free translation with MS2 or fr phage RNAs and RNA protein III of phage fd. PMID- 8471668 TI - Multiparameter flow cytometric analysis of the effects of indomethacin on adipocyte differentiation in A31T6 cells. AB - A31T6 proadipocytes, derived from BALB/c-3T3 clone A31, develop responsiveness to differentiation-promoting agents at density-arrest and differentiate into adipocytes, as determined by the accumulation of cytoplasmic lipid droplets. A flow cytometric assay is being employed to monitor the acquisition of aspects of the differentiated phenotype. In this study, the assay is used to monitor both the rate of differentiation, as defined by the appearance of cells containing lipid droplets and the rate of adipocyte maturation, which involves measurement of increases in cytoplasmic lipid in cells already committed to the differentiation programme. Specifically, we show that: 1) treatment with a combination of indomethacin and dexamethasone causes the maximum percentage differentiation in the population, 2) addition of indomethacin in combination with either dexamethasone or insulin increases the rate of differentiation, and 3) indomethacin selectively increases the maturation of adipocytes, measured as an increase in the amount of lipid per cell. The cytometric assay used in these experiments has allowed determination of the effects of indomethacin on aspects of the adipocyte phenotype that cannot be measured by standard techniques. PMID- 8471669 TI - In vitro BrdUrd incorporation of colorectal tumour tissue. AB - This study describes a novel in vitro method for the incorporation of the thymidine analogue, bromodeoxyuridine (BrdUrd), in fresh colorectal tumour tissue. Disaggregation by pronase, collagenase and DNAse resulted in high cell yields of viable single cell suspensions, representative of the original tumour, which could be infiltrated with BrdUrd. A modified ELISA identified optimal incubation times and BrdUrd concentrations. This technique has been used in preliminary studies to investigate two important areas intrinsic in the analysis of BrdUrd colorectal cell proliferation data: 1) to determine the effects of the individual constituents of the cell culture media, in particular glutamine, on BrdUrd incorporation in suspensions of colorectal cells and 2) to examine the denaturation step. This method will have wide applicability in investigations of cell proliferation status in both normal and diseased tissue. PMID- 8471670 TI - Biochemical and morphological characterizations of DU-145 cell mortality in rabbit embryo-fetal fluid. AB - Rabbit embryo-fetal fluid (EFF) contains regulatory factors of cell proliferation which increase the duration of the cell cycle, induce a quiescent status in some cells and lead up to cell death in others. The objective of this study was to demonstrate which of the two processes, namely necrosis or apoptosis, was responsible for the cell death. Inhibitors of protein synthesis, and nuclease and phospholipase A2 activities did not restore the viability of the cells treated with EFF. Using a combination of DNA labelling and extraction, it was possible to show that a large proportion of DNA was fragmented in the cells released in the supernatant while only a very small portion of DNA was fragmented in the monolayer cells. EFF did not induce fragmentation of DNA into nucleosome-sized subunits as analysed using polyacrylamide gel electrophoresis. Nevertheless, using cytofluorometric analysis, it was possible to demonstrate that 50% of the cells released in the supernatant contained a lower quantity of DNA per cell than in the control cells. This was also observed with EFF-treated monolayer cells but not in the control monolayer cells. The reduction of the DNA content per monolayer cell became significant at 48 h of treatment with EFF. Electron microscopic analysis did not reveal blebbing of the cells. However, depletion of glycogen, condensation of mitochondria and increasing number of lysosomes and residual bodies were observed upon treatment with EFF. From these experiments we conclude that the DU-145 cells treated with EFF do not die by apoptosis, but rather seem to die by necrosis. PMID- 8471671 TI - The role of the IGF-1 receptor in the stimulation of cells by short pulses of growth factors. AB - Balb/c 3T3 cells require prolonged stimulation by serum or growth factors to enter DNA synthesis. However, in p6 cells, a derivative cell line from 3T3 cells which constitutively over-express the insulin-like growth factor-1 (IGF-1) receptor, a serum pulse of only 1 h is sufficient for maximal stimulation. Furthermore, maximal stimulation of DNA synthesis is also obtained when 3T3 cells, serum-stimulated for only 1 h, are subsequently incubated with IGF-1. Our results indicate that short pulses of growth factors render 3T3 cells capable of responding to IGF-1, either by increasing the number of IGF-1 receptors or by providing a new substrate for the activated receptor. PMID- 8471672 TI - Hydroxyurea exposure alters mouse testicular kinetics and sperm chromatin structure. AB - The effects of hydroxyurea (HU) on testicular cell kinetics and sperm chromatin differentiation were investigated in mice. Whole testis, minced testicular cell suspensions and caudal epididymal sperm cells were obtained at 8 and 29 days after i.p. injections containing 0, 25, 50, 100, 200, 400 and 500 mg/kg HU x 5 days. Testis weights were unaffected by 25 mg/kg HU while 500 mg/kg caused up to a 50% loss of testicular weight by 29 days. Flow cytometrically measured acridine orange (AO) stained testicular cells revealed altered population ratios at the highest dosages at 8 days and for all dosages except 25 mg/kg HU at 29 days. At 8 days, 400-500 mg/kg HU caused a near depletion of tetraploid cells. Flow cytometry of AO stained sperm, previously treated with acid to potentially induce DNA denaturation, was used to follow the shift from normal chromatin structure to an abnormal form with increased sensitivity to DNA denaturation in situ. The extent of DNA denaturation was quantitated for each cell by the computer-derived value alpha t, alpha t = [red/(red+green) fluorescence]. The flow cytometry measures, standard deviation of alpha t (SD alpha t), mean of alpha t (X alpha t) and cells outside the main peak of alpha t (COMP alpha t), gave similar dose response curves to the sperm head morphology assay. SD alpha t was more sensitive than the X alpha t as a measure of HU-induced alteration of chromatin structure. The major conclusions reached are that HU inhibits DNA synthesis, probably by inhibiting ribonucleotide reductase, causing maturation depletion of pachytene spermatocytes and, subsequently, depletion of meiotic daughter cells and differentiated cell types leading to mature sperm. This inhibition of DNA synthesis is related to an alteration of sperm chromatin structure and abnormal sperm head morphology. PMID- 8471673 TI - Pre-irradiation of tissue culture flasks leads to diminished stem and progenitor cell production in long-term bone marrow cultures. AB - Empty plastic tissue culture flasks were exposed to X-irradiation doses of 0.3 10.0 Gy, prior to the establishment of long-term bone marrow cultures. During the course of a 10 week culture period, all irradiated plastic flasks exhibited a dramatic decrease in the number of both haemopoietic stem cells and myeloid progenitor cells, in the non-adherent layer, when compared with controls. This decrease was not due to a decrease in the number of non-adherent cells produced. Histological examination of non-adherent cells showed an increase in mature granulocytic cells with few blast cells. Morphologically, the adherent layers of irradiated flasks demonstrated a delay in appearance or absence of fat cell production. X-irradiation of glass tissue culture flasks had no deleterious effect. PMID- 8471674 TI - Cell proliferation kinetics of the bile duct epithelium of the rat. AB - Cell proliferation kinetics of the extrahepatic bile duct were studied by flash and cumulative labelling methods and immunohistochemical techniques. We compared the cell kinetics of the epithelium of the intra- and extra-pancreatic bile ducts and of the bile duct of the ampulla in rats administered intraperitoneally with bromodeoxyuridine (BrdUrd). After a single injection of BrdUrd (flash labelling), labelled cells appeared in the lower portion of the downgrowths of the epithelium in the intra- and extra-pancreatic bile ducts. A gradual accumulation of the labelled cells at the surface epithelium was observed during the cumulative labelling. After cumulative labelling the labelled cells gradually decreased in number and were finally confined to the degenerative cell zone of the surface epithelium 30 days later. Similarly, after a single injection of BrdUrd, the labelled cells in the bile duct of the ampulla appeared at the lower half of the crypt from where they migrated to the upper portion during cumulative labelling. These findings indicate that epithelial cells of the bile duct are renewed at the lower portion of the downgrowths of the epithelium, or crypt, and shed from the surface epithelium or upper portion of the fold. The labelling indices reached 23.83 +/- 7.47% in the intra-pancreatic bile duct, 14.74 +/- 7.99% in the extra pancreatic bile duct and 43.42 +/- 4.40% in the bile duct of the ampulla at the end of 70 h cumulative labelling. The fluctuating values of the labelling index were higher in the bile duct of the ampulla than in the intra- or extra pancreatic bile ducts. These results indicate that the bile-duct epithelium undergoes a slower renewal rate than the other parts of the gastrointestinal tract, and that the renewal time of the epithelial cells is shorter at the bile duct of the ampulla than at the intra- or extra-pancreatic bile ducts. PMID- 8471675 TI - Homosexual warriors. PMID- 8471676 TI - Hippocampus-amygdala volumes and psychopathology in chronic schizophrenia. AB - Volumes of the mesiotemporal structures (hippocampus-amygdala complex) were measured in 19 men who were chronic multiepisode schizophrenics and 18 age matched healthy controls using T1-weighted contiguous coronal magnetic resonance images of 3.1-mm width. Using the level of the mammillary bodies as an anatomical landmark, the whole hippocampus-amygdala complex was divided into an anterior section (mainly containing amygdaloid tissue) and a posterior section (mainly containing the hippocampal formation). Total mesiotemporal tissue volume was reduced significantly in the patient group compared to controls (-11%), with significant reductions in both left (-20%) and right (-15%) hippocampal sections. Reduced limbic tissue volume was associated with increased severity of psychopathology. Severity of positive psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] psychosis factor) was correlated significantly with right and left total mesiotemporal volumes (Spearman rho's = -0.61 p < 0.01). Negative symptom scores (BPRS anergia factor, Scale for Assessment of Negative Symptoms [SANS] global items) were not significantly correlated with any mesiotemporal tissue volumes. The data corroborate and extend previous findings of temporolimbic structure volume reduction in schizophrenia, and suggest that the positive psychotic symptoms of schizophrenia are associated with anatomic anomalies in mesiotemporal structure. PMID- 8471677 TI - 5-HT1A agonists disrupt memory of fear conditioning in mice. AB - A series of experiments was carried out to analyze the effects of the 5-HT1A agonists tandospirone or buspirone on the retention of fear conditioning in mice. Fear was produced by pairing tone and shock in a conditioned emotional response (CER) paradigm and strength of conditioning was assessed by measuring suppression of drinking in presence of tone. Fear conditioning was disrupted if tandospirone and buspirone were administered before the conditioning session but not before the test trial. Diazepam disrupted conditioning at both times. Tandospirone did not disrupt performance if conditioning was tested 1 hr rather than 24 hr after training, suggesting that disrupted memory rather than impaired acquisition was responsible for the deficit. The effect of tandospirone on fear conditioning could be reversed by administration of d-amphetamine prior to the retention test, which suggests that information was stored but is inaccessible to normal retrieval cues. Tandospirone and buspirone also retarded extinction, a clear indication that the disruption caused by these drugs is unrelated to their anxiolytic action. PMID- 8471678 TI - Severe cognitive impairment in elderly schizophrenic patients: a clinicopathological study. AB - The severe cognitive impairment that affects many of the elderly schizophrenic patients could represent the outcome of schizophrenia in old age for the very severe and chronically ill patients or may be the result of lengthy institutionalization and somatic treatment. Alternatively, it could be due to the presence of concurrent dementing disorders, such as Alzheimer's disease (AD) or multi-infarct dementia. Using an identical neuropathological protocol, brain specimens from schizophrenic patients who showed evidence of severe cognitive impairment were compared with 12 age-matched control cases and the same number of age-matched cases of neuropathologically confirmed patients with AD. Despite their relatively advanced age (mean age 77.1 years +/- 2.8), none of the schizophrenia cases showed sufficient degree of senile plaques and neurofibrillary tangle formations to confirm a diagnosis of AD. Other neurodegenerative disorders associated with dementia were also not identified. These studies suggest that alternative explanations need to be sought for the severe cognitive impairment commonly encountered in elderly schizophrenic patients. PMID- 8471679 TI - A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant. AB - The noradrenaline (NA) hypothesis of depression is founded primarily on preclinical and clinically indirect evidence. In two three-compartment randomized parallel clinical trials conducted serially, we examined the significance of NA uptake for antidepressant activity. The racemic compound oxaprotiline (hydroxymaprotiline) is a highly specific inhibitor of NA uptake, whereas its R-( ) enantiomer levoprotiline is totally devoid of this property. Oxaprotiline significantly resembled amitriptyline in its antidepressant potential. Conversely, levoprotiline significantly resembled placebo in antidepressant potential. Therefore, NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant. PMID- 8471681 TI - Does ECT permanently alter seizure threshold? AB - Recent research has raised the possibility that electroconvulsive therapy (ECT) results in a persistent elevation of seizure threshold among males. In this study, seizure threshold, quantified by the method of limits procedure, was assessed at the first and last treatments of 148 consecutive depressed patients. Patients with and without a prior history of ECT did not differ in seizure threshold at the first treatment, seizure duration at the first treatment or averaged across all treatments, or in the magnitude of the seizure threshold increase over the ECT course. No evidence was obtained that history of ECT was associated with alterations of seizure threshold or seizure duration. PMID- 8471680 TI - Thyrotropin response to thyrotropin-releasing hormone in patients with dementia of the Alzheimer type. AB - Eleven patients with senile dementia of the Alzheimer type and 11 age-matched control subjects were given the thyrotropin-releasing hormone (TRH) test. The two groups did not differ with respect to peak thyrotropin (TSH) response or TSH levels at baseline, 20, 30, and 45 min after TRH injection. There were significant differences between the groups on Hamilton Depression Rating Scale scores (p < 0.03), although neither group met clinical criteria for depression. Items that were significantly different pertained to depressed mood, loss of interest, loss of insight, suicidal ideation, and obsessional symptoms. PMID- 8471682 TI - Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurologic patients: a replication of neuroendocrine features of major depression. AB - A blunted thyrotropin (TSH) and an unaltered prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) are widely recognized in neuroendocrinology of depression. We studied effects of repeated TRH administration of 1 mg/day for 10 days on the pituitary-thyroid axis function and PRL secretion in 16 euthyroid patients with neurological disorders. Although levels of serum thyroid hormones and of nonstimulated PRL were not affected by the treatment, baseline TSH levels were markedly inhibited. A blunted response of TSH to TRH was found without a significant effect on a PRL response to TRH after long-term treatment with TRH in four patients in whom a TRH test was performed. These changes are similar to those in depressed patients. TRH administration in this manner replicates a lowered sensitivity of thyrotrophs of the pituitary with a normal responsibility of lactotrophs in depression. PMID- 8471683 TI - Spectral and topographic analysis of EEG in schizophrenic patients. AB - The authors performed spectral analysis of electroencephalograms (EEG), recorded awake, with eyes closed, in 13 patients with schizophrenia and 9 age-matched individuals without psychiatric diagnosis. We tested several possible parameterizations of the data, and two data-reduction strategies; these yielded similar results. Comparison of the two groups revealed a relative increase in alpha frequency activity in the frontal regions in the patient group. The authors believe that this finding is consistent with data from neuropsychologic tests, metabolic imaging studies, and evoked potential studies that suggest impaired activation of frontal brain areas in patients with schizophrenia. PMID- 8471684 TI - Desipramine reduces plasma but not brain thyroxine levels. PMID- 8471685 TI - Panic attacks induced by doxapram. PMID- 8471686 TI - A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. PMID- 8471687 TI - Elevated plasma dopamine in posttraumatic stress disorder: a preliminary report. PMID- 8471688 TI - Primate models, supermonkeys, and weaklings. PMID- 8471689 TI - Postural sway in children from pedigrees exhibiting a high density of alcoholism. AB - A total of 98 children participated in a study of the neurobehavioral characteristics of individuals from pedigrees in which there was a high density of alcoholism. Two groups of children were evaluated (High and Low Risk) using a sensitive movement platform and a variety of methods to challenge the motor system. High-Risk children showed a greater decrement in postural steadiness when visual input was removed than did Low-Risk children. Additionally, the monopedal stances revealed hemispheric differences in postural sway as a function of risk status. The amount of sway exhibited was correlated with the latency of P300 recorded using a visual task. Both appear to be indicators of neuropathological changes. The present results suggest that postural sway may be a neurobehavioral marker for alcoholism risk. PMID- 8471690 TI - Ambulatory polysomnography of never-depressed borderline subjects: a high-risk approach to rapid eye movement latency. AB - The sleep parameters of never-depressed borderline subjects and age- and sex matched normal controls were compared by continuous 48-hr ambulatory electroencephalographic (EEG) monitoring. Borderline subjects had a significantly shorter rapid eye movement latency, normal architecture of rapid eye movements sleep, and had familial risks for mood disorders four times greater than in the families of controls. Reduced latency of rapid eye movement can be a trait indicator of liability to depression, present before the clinical appearance of the disorder, and demonstrable in a putative high-risk population. PMID- 8471691 TI - The reliability of P50 suppression as measured by the conditioning/testing ratio is vastly improved by dipole modeling. AB - Suppression of auditory P50 evoked potential amplitude to the second of a pair of clicks is potentially important in psychiatric research because it has been shown to be abnormal in both schizophrenics and their relatives. However, its clinical utility using the standard single-channel electroencephalographic (EEG) peak picking methodology is under question because of low test-retest reliability. Dipole Components Modeling of the P50 component was attempted as a method for increasing the reliability of the P50 suppression measure. It was hypothesized that this procedure might work because of pooling of noise from the two responses and because of the use of topographic information. Six replications of a P50 suppression paradigm in 12 subjects were analyzed. Reliability using peak picking was 0.27, and was significantly increased to 0.63 using dipole modeling. Dipole modeling was helpful not only for better modeling the P50 when it was present, but also for deciding that there was no P50 response in one subject. PMID- 8471692 TI - Lack of evidence for Huntington's disease-like cognitive dysfunction in obsessive compulsive disorder. AB - Cognitive deficits in patients with structural lesions of the basal ganglia (e.g., Huntington's disease) commonly include slowed processing, reduced verbal fluency, difficulty switching set, impaired egocentric spatial ability, poor recall, and impaired acquisition of motor skills. The goal of this study was to determine if patients with obsessive-compulsive disorder (OCD) would have a similar pattern of cognitive dysfunction. A battery of neuropsychological tests, including reaction time-based measures of cognitive processing speed and a test of procedural, motor-skill learning, was administered to 17 unmedicated OCD patients and 16 age-and education-matched normal controls. Eleven individuals with trichotillomania, matched with the OCD patients on age, education, age at symptom onset, depression, and anxiety were also tested. Contrary to expectation, neither the OCD nor trichotillomania patients were impaired on any of the measures in the battery. The essentially normal performance by these patients suggests that the brain regions responsible for cognitive dysfunction in patients with Huntington's disease may differ from those associated with OCD. PMID- 8471693 TI - Cerebellar vermal size in schizophrenia: a male effect. AB - Magnetic resonance (MR) was used to examine the cerebellar vermis in 23 patients with schizophrenia and 16 matched controls. MR midsagittal images were processed with computerized image analysis to control partial volume effects as precisely as possible. No between-group differences were found for vermal-to-cerebrum ratio. When gender differences were examined, male patients showed a lower vermal to-brain ratio than their female counterparts, mainly because of a reduction of the lobules I-V. PMID- 8471694 TI - Effects of gender and social isolation on electroencephalogram and neuroendocrine parameters in rats. AB - Social separation/isolation from either maternal or peer influence can induce a biobehavioral response in rodents and nonhuman primates seeming to mimic certain aspects of human psychopathology. To further explore this paradigm, the effects of 6 weeks of social isolation on electroencephalographic (EEG) recordings and hypothalamic-pituitary-adrenal (HPA) functioning were studied in male and female adult rats. Gender differences were observed in EEG and HPA axis functioning in these rats. Female rats, overall, were found to have higher levels of EEG slow wave activity over the entire recording period, suggesting more intense levels of slow-wave sleep in those animals. Female rats were also observed to have overall higher plasma corticosterone concentrations and a lower anterior pituitary corticotropin-releasing factor (CRF) receptor density compared with male rats. The male rats, however, showed greater changes in response to social isolation than female rats. EEG power was increased as a result of social isolation in the male animals during the first 30-100 min of the recording. Reductions in the number of CRF receptors were also observed in the brains of the socially isolated rats in several cortical areas; however, again this effect was more prominent in the male animals. These studies suggest that gender is an important variable in determining the biobehavioral response to social isolation. PMID- 8471695 TI - Platelet serotonin-2 receptors in obsessive-compulsive disorder. AB - To examine the role of serotonin-2 (5-HT2) receptors in obsessive-compulsive disorder (OCD), we studied 5-HT2 receptors in platelets obtained from patients with OCD (n = 20) during a drug free baseline period, as well as in normal control subjects (n = 25). The maximum number of binding sites (Bmax) and the apparent dissociation constant (Kd) of 5-HT2 receptors were determined by receptor binding techniques using 125I-lysergic acid diethylamide (LSD) as radioligand. We observed that the mean Bmax of 125I-LSD binding in platelets of patients with OCD was not significantly different when compared with normal control subjects. There was also no significant difference in Kd values between patients with OCD and normal control subjects. To examine whether the baseline 5 HT2 receptors are related to the severity of illness, we determined the relationships of the baseline Bmax and Kd with baseline scores of the Hamilton Depression Rating Scale (HDRS), the Yale-Brown Obsessive-Compulsive Scale (Y BOCS), and the National Institute of Mental Health (NIMH) Obsessive-Compulsive scale (GOCS). We found no significant correlation between baseline Bmax and Kd with the baseline HDRS, Y-BOCS, or NIMH-GOCS scores. Our results do not indicate abnormal 5-HT2 receptors in platelets of patients with OCD. PMID- 8471696 TI - Serotonin uptake inhibition by the monoamine oxidase inhibitor brofaromine. AB - The selective, reversible monoamine oxidase (MAO) A inhibitor brofaromine inhibits serotonin (5-HT) uptake in animal models in vitro and in vivo. We investigated whether such an effect can be demonstrated at clinical doses in humans by treating three groups of six volunteers with either placebo, 15 mg phenelzine three times a day, or 75 mg brofaromine twice a day in a 2-week experiment. As an indirect, although relevant parameter, binding of 3H-paroxetine to the 5-HT uptake sites on blood platelets was assessed. Moreover, whole-blood 5 HT as a measure of platelet 5-HT, and serum homovanillic acid (HVA) to tentatively estimate MAO inhibition, were determined. Brofaromine reduced 3H paroxetine binding to platelets compared with placebo by 20%-25% throughout the treatment period, significance being reached on the last treatment day. In contrast, phenelzine tended to increase 3H-paroxetine binding. Both drugs increased whole-blood 5-HT to approximately 140%-150%. Brofaromine moderately and on some days significantly decreased serum HVA, whereas phenelzine only tended to do so. Our results suggest that brofaromine at the clinically used dosage of 150 mg/day does indeed inhibit 5-HT uptake, as evidenced by measurements of 3H paroxetine binding to platelets. PMID- 8471697 TI - Platelet cytosolic free-calcium concentration is increased in aging and Alzheimer's disease. PMID- 8471698 TI - Seizure duration, estimation: definition vs. ECT device model. PMID- 8471699 TI - [Nursing consultations in primary health care]. PMID- 8471700 TI - [The prior appointment program: what was expected and what has been gained?]. PMID- 8471701 TI - [Maternity in adolescents at high social risk]. AB - OBJECTIVE: To analyse for the 1987-1990 period the indicators of prenatal care and the social-health follow-up of adolescent girls included in the mother-child programme of Ciutat Vella (Barcelona). This programme was aimed at pregnant women resident in the district and with high social risk profiles. DESIGN: Descriptive and retrospective study. MEASUREMENTS AND MAIN RESULTS: 175 adolescent mothers were included in the programme during the period under study. This represented 82.9% coverage of all births in the district to this age group. In 10.9% of cases the mother stated she lived alone. 10.2% had had a previous child. There were drug addiction antecedents in 5% of the mothers. The first prenatal check took place during the first three months only in 56% of the pregnancies, with the proportion of low weight births (LWB: weight at birth below 2,500 grams) at 13.1%. During the period under study the proportion of pregnant women checked in the first three months went up from 45.6% to 62.5%, while the proportion of LWB's went down from 19.3% to 6.3%. CONCLUSIONS: There has been both a striking improvement in the indicators of prenatal care and less low weight births during the first four years of this programme. It is worth noting the worrying fact that one third of pregnant adolescents do not attend for a prenatal check-up before three months of their pregnancy have elapsed. PMID- 8471702 TI - [The epidemiology of rheumatic diseases in the Principality of Asturias]. AB - OBJECTIVE: To determine the prevalence of rheumatic illnesses in the Principality of Asturias. DESIGN: Crossover study, consisting of an interview and a medical examination, administered to 702 people selected in a random fashion, in line with multi-stage and proportional sampling. Validated criteria for the diagnosis of rheumatic pathology were applied. SETTING: Urban and rural population throughout the Autonomous Community of the Principality of Asturias. RESULTS: There was a 75.6% response (702 people). In these a 23.8% prevalence of arthrosis was found, with a significantly higher proportion among older people and women. The second most common condition was rheumatism in soft parts; and then lumbalgia, which predominates in middle age. Inflammatory arthropathies are much less common (2.5%) in the general population. 6.1% of the sample presented a rheumatic pathology that could not be adequately defined. CONCLUSIONS: Rheumatic illnesses are extremely common among the general population. Arthrosis, rheumatism of the soft parts and lumbalgia are the most customary conditions. Their prevalence is much greater than that of inflammatory rheumatism. PMID- 8471703 TI - [The companion at the clinical interview]. AB - OBJECTIVE: To discover how often patients attend a clinical interview with a companion; and to define this companion by the variables of age, gender, reason for the interview, the relationship (friend or relation) and his/her typology. DESIGN: This was a descriptive, prospective study. SETTING: The study was carried out in the Almanjayar and Cartuja Health Centres. PATIENTS AND OTHER PARTICIPANTS: The 899 people who attended for a consultation during the last week of July, 1991, were included in the study. MEASUREMENTS AND MAIN RESULTS: Companions were present in 39.15% of the clinical interviews. Patients under 20 and those with acute complaints were those who most commonly attended with a companion. 94% of the companions were family members: most commonly, the mother or the husband/wife. 18.7% of the companions caused conflict. CONCLUSIONS: The companion can be seen as an important element of the health network as well as a social support. Companions with a collaborative attitude can be used to find out clinical data and family background during the interview; whereas difficult or sick companions require a particular approach to prevent their interfering with the development of the clinical interview. PMID- 8471704 TI - [The introduction of a program of preventive activities at a health center]. AB - OBJECTIVE: To define the effect of preventive activities on the population served by a health centre; and to make a comparison between the two different shifts, on one of which a preventive programme functioned, whereas on the other it did not. DESIGN: A descriptive study, using systematic random sampling and internal crossed auditing of the health centre's clinical records. SETTING: An urban primary care centre. PATIENTS AND OTHER PARTICIPANTS: Two samples of 175 patients from both morning and afternoon shifts were compared. INTERVENTIONS: The following were studied: antitetanus and German measles vaccinations; control of arterial tension; control of cholesterolaemia; a questionnaire on tobacco and alcohol consumption. MEASUREMENTS AND MAIN RESULTS: No differences were observed in the homogeneity of the tests carried out (DVS = 413.28, p = NS; chi squared = 9.67, p = NS). Important differences were observed in the percentages for the preventive activities carried out. These differences were in favour of the morning shift, where the tests were part of the programme, and were statistically significant for all tests. Differences were greater in the younger age-groups. CONCLUSIONS: Introducing and integrating a programme of preventive activities into the daily activity of the consulting room, significantly improves the effectiveness of these activities. We believe therefore that the introduction of such activities in the form of a programme should be encouraged. PMID- 8471705 TI - [Self-perceived health, the use of services and drug consumption in a noninstitutionalized older population]. AB - OBJECTIVE: To describe the self-perceived health status, the use of services and drugs consumption of the elderly population in Toledo province. DESIGN: Descriptive crossover study. SETTING: Primary Care, Toledo province. PATIENTS AND OTHER PARTICIPANTS: 591 people over 65 and not in an institution. Stratified according to age, gender and place of residence. MEASUREMENTS AND MAIN RESULTS: A validated questionnaire was administered to the elderly people in their homes. 86.6% of them suffered from at least one chronic illness: the average was 2.30 per person. 55.2% referred to chewing problems; 43.2% to difficulty in walking; 69.2% to sight problems; and 40.3% to hearing trouble. 59.6% had visited the general doctor at least once during the previous month. During the previous two weeks, 71.6% had taken at least one medicine prescribed by the doctor; and 21.2% had taken medicine on their own initiative. CONCLUSIONS: There was coincidence between the perception of their own health status, the number of chronic complaints from which they suffered, the frequency of use of the health services and the number of drugs consumed. Women and those over 75 were those who described their own health in the most negative way. PMID- 8471706 TI - [Osteitis condensans ilii]. AB - OBJECTIVE: The description of a case of osteitis condensans ilii. DESIGN: Descriptive. SETTING: Base health area. PATIENTS AND OTHER PARTICIPANTS: A 24 year-old puerperal woman. INTERVENTIONS: Analgesic treatment. MEASUREMENTS AND MAIN RESULTS: We were presented with the history of a woman with low lumbar pain of a mechanical character, after a dystocial birth two months previously. The radiology showed a triangular bony condensation on the edge of the sacroiliac joints. CONCLUSIONS: Osteitis condensans ilii is a benign structure, almost only ever found in women who have borne children. Its presentation is asymptomatic or nonspecific (low lumbalgia). Its very specific radiological image needs to be distinguished carefully in order to avoid diagnostical confusion with ankylosing spondylitis and other causes of sacroiliitis. PMID- 8471707 TI - [The degree of agreement in the radiological interpretation of the growth of left cardiac cavities between the radiologist, the family physician and residents in family and community medicine]. AB - OBJECTIVE: To discover the level of agreement about the radiological interpretation of the growth of left-side cardiac cavities, between the referring radiologist (Rx), a family doctor (FD) and three interns studying the third year of family and community medicine (IFCM). DESIGN: Observational crossover study. SETTING: Primary Care (PC). The Perpetuo Socorro Health Centre in Huesca. PATIENTS AND OTHER PARTICIPANTS: Hypertense patients included in the programme of one of the general medicine sections. MEASUREMENTS AND MAIN RESULTS: There were 69 thorax radiographies (TXR), 10 of which were repeated in order to assess the level of agreement between different evaluations by the same observer (intra observer). Out of these 69, there was agreement between observers in 39 cases (66.10%) with Kappa Index (KI) 0.39 +/- 0.12 for two IFCMs (2 and 3); in 44 (74.57%), with KI 0.55 +/- 0.12 for the first IFCM; and in 40 (67.10%), with KI 0.39 +/- 0.12 for the FD. The intra-observer agreement was 80% with KI 0.50 +/- 0.29, 60% with KI 0.20 +/- 0.23 and 90% with KI 0.80 +/- 0.23 for the three IFCM's. It was 70% with KI 0.34 +/- 0.27 for the FD and 80% with KI 0.48 +/- 0.29 for the Rx. CONCLUSIONS: Both the inter- and intra-observer agreement levels were insufficient. We propose that our training during the period of specialisation should be strengthened on the most useful questions from the PC point of view. Studies of this sort need to be carried out in PC in order to obtain maximum benefit from these complementary tests. PMID- 8471708 TI - [The early detection of oral cancer]. PMID- 8471709 TI - [The intradermal reaction or Mantoux test. The status of the question]. PMID- 8471710 TI - [The organization of a health center starting with citizen participation. The example of the Centro de Salud Vicente Soldevilla]. PMID- 8471711 TI - [Auricular fibrillation in a young patient]. PMID- 8471712 TI - [The guarantee of the quality of prenatal care at a rural health center]. PMID- 8471713 TI - [Fanconi's anemia]. PMID- 8471714 TI - [Participatory research in Cuenca Lechera, Departamento de San Jose]. PMID- 8471715 TI - [The evaluation of a diabetes program in primary care]. PMID- 8471716 TI - [Considerations on the relevance of original publications]. PMID- 8471717 TI - Elementary theory of Brownian motion of trapped domains in lipid monolayers. AB - An elementary theoretical model is described for the Brownian motion of circular lipid domains electrostatically trapped within larger circular lipid domains in monolayers at the air-water interface. Earlier work is briefly reviewed, in which it is shown that the r.m.s. amplitude of the trapped Brownian motion follows a simple Maxwell-Boltzmann distribution, and can be used to determine the absolute value of the difference of dipole densities in the two co-existing phases [mu]. A comparison of this dipole density difference with that obtained from surface potential measurements provides a critical test of the theoretical model. It is also shown that the kinetics of Brownian motion can be analyzed to provide information on monolayer fluid mechanics and to provide a further test of the model. It is pointed out that the ease with which domain movements can be observed in the fluorescence microscope, coupled with the fact that the energies involved are only of the order of magnitude of kT, suggests that lipid monolayers can be used to detect weak specific intermolecular bonds between ligands incorporated in the lipid monolayer, and receptors fixed in the aqueous subphase. PMID- 8471718 TI - Glycosphingolipid acyl chain orientational order in unsaturated phosphatidylcholine bilayers. AB - The glycosphingolipid, galactosyl ceramide (GalCer), was studied by 2H nuclear magnetic resonance (NMR) in fluid phospholipid bilayer membranes, with regard to arrangement of its acyl chain. For this purpose, species with perdeuterated 18 carbon fatty acid (18:0[d35]GalCer) or with perdeuterated 24-carbon fatty acid (24:0[d47] GalCer) were dispersed in bilayers of the 18-carbon phospholipid, 1 stearoyl-2-oleoyl-phosphatidylcholine (SOPC). For 18:0[d35] GalCer, smoothed profiles of the order parameter, SCD, were found to be very similar to one another over the range of glycolipid concentration, 5-40 mol%. In addition, they were very similar to orientational order parameter profiles well known from the literature on phospholipid and glycolipid acyl chains (which deals in general with membranes of homogeneous chain length in the range 14-18 carbons). Corresponding order parameter profiles for the long-chain species, 24:0[d47] GalCer, were also similar to one another for glycolipid concentrations between 5 and 40 mol%. Their shapes, however, were distinctly different from those of the shorter chain analogues. SCD profiles for the two species were quantitatively similar to a membrane depth of C15. SCD values at C16 and C17 were approximately 20 and 30%, respectively, higher for the long-chain glycosphingolipid than for its short-chain analogue in SOPC. Nitroxide spin labels attached rigidly to C16 of the long-chain glycolipid in SOPC gave electron paramagnetic resonance (EPR) order parameters that were twice as high as for a spin label at C16 on the shorter chain glycolipid. Comparison was made between spectra of 24:0[d47] GalCer in SOPC and fully hydrated bilayers of the pure 24:0[d47] GalCer, a system that is considered to be partially interdigitated in fluid and gel phases. The resultant 2H NMR order parameter profiles displayed similar features, indicating that related organizational properties exist in these fluid systems. Effective chain length of 24:0[d47] GalCer within the SOPC membrane was calculated using the method of Schindler and Seelig (1975. Biochemistry, 14:2283-2287). The result suggested that the long-chain fatty acid should protrude roughly one third of the host matrix chain length across the bilayer midplane. However, a treatment of the same order parameters making very few assumptions about chain conformation indicated a high degree of orientational flexibility for the "extra" length of the long chain fatty acid. It seems likely that a realistic treatment of the long chain fatty acidin a shorter chain fluid host matrix considers interdigitation as a subset of the conformational possibilities, many of which are rapidly interconverting on the NMR timescale of 10-4_10-5 s and longer lived on the EPR timescale of 10-8_10-9 s. PMID- 8471719 TI - Molecular dynamics simulation of Pf1 coat protein. AB - The results of molecular dynamics simulations of Pf1 coat protein are described and compared to experimental NMR data on both the membrane bound and structural forms of this viral coat protein. Molecular dynamics simulations of the 46 residue coat protein and related model sequences were performed according to a simple protocol. The simulations were initiated with the polypeptides in a completely uniform alpha helical conformation in a dielectric continuum (epsilon = 2) and the motions of individual residues were followed as a function of time by monitoring the angular fluctuations of amide NH bond vectors. The simulations of Pf1 coat protein were able to identify the same mobile and structured segments found in experimental NMR studies of the membrane bound form of the protein (Shon, K.-J., Y. Kim, L. A. Colnago, and S. J. Opella. 1991. Science (Wash. DC). 252:1303-1305). Significantly, in addition to mobile amino and carboxyl terminal regions, a mobile internal loop was found that connects the rigid hydrophobic and amphipathic helices in the protein. NMR experiments show that this mobile loop is present in both the viral and membrane bound forms of the protein and that it plays a role in viral assembly (Nambudripad, R., W. Stark, S. J. Opella, and L. Makowski. 1991. Science (Wash. DC) 252:1305-1308). The results of simulations of several alanine based 46 residue polypeptides with some of the charged residues present in the Pf1 coat protein sequence suggest that interactions between the Asp 14 and Asp 18 sidechains and the peptide backbone are responsible for the formation of the mobile loop. The agreement between the results of the calculations presented here and the previously reported NMR experiments suggest that molecular dynamics simulations might be useful in the prediction of the secondary structure and dynamics of individual residues in membrane and structural proteins with predominantly alpha helical secondary structure. PMID- 8471720 TI - Fluorescence lifetime imaging microscopy (flimscopy). Methodology development and application to studies of endosome fusion in single cells. AB - A new method of fluorescence microscopy for cell imaging has been developed that takes advantage of the spatial variations of fluorescence lifetimes in single cells as a source of image contrast, and thus it is named "fluorescence lifetime imaging microscopy (flimscopy)". Since time-resolved fluorescence measurements are sensitive to molecular dynamics and interactions, flimscopy allows the molecular information to be visualized in single cells. In flimscopy measurements, several (nanosecond) time-resolved fluorescence images of a sample are obtained at various delay times after pulsed laser excitation of the microscope's entire field of view. Lifetimes are calculated pixel-by-pixel from these time-resolved images, and the spatial variations of the lifetimes are then displayed in a pseudocolor format (flimscopy image). The total data acquisition time needed to obtain a flimscopy image with the diffraction-limited spatial resolution (approximately 250 nm) is decreased to just approximately 30 s for approximately 300 fluorescent molecules/micron2. This was achieved by developing a high-frequency (400 kHz) nanosecond-gating (9 ns full width at half height) signal accumulation system. This technique allows the extent of resonance energy transfer to be visualized in single living cells, and is free from the errors due to variations in path length, light scattering, and the number of fluorophores that necessitate complex corrections in steady-state microfluorometry and fluorescence ratio imaging microscopy. Flimscopy was applied here to observe the extent of fusion of individual endosomes in single cells. Results revealed the occurrence of extensive fusion between primary endocytic vesicles and/or sorting endosomes, thereby raising the possibility that the biogenesis of sorting endosomes involves multiple fusions of primary endocytic vesicles. PMID- 8471721 TI - Physical characterization of cyclosporine binding sites in lymphocytes. AB - The binding of cyclosporine to human peripheral blood lymphocytes (PBLs) was studied by measuring the fluorescence emission spectrum and lifetime of the fluorescent and immunosuppressive cyclosporine derivative dansyl-cyclosporine (DCs). The emission maximum and fluorescence lifetime of DCs were characterized in several solvents. The fluorescence emission maximum and lifetime of DCs increased at a high dielectric constant. The fluorescence lifetime decay curve of DCs was a monoexponential function in all solvents tested. Fluorescence micrographs of lipid vesicles and erythrocytes labeled with DCs exhibit uniform staining patterns, whereas PBLs show heterogeneous DCs labeling. DCs exhibits a relatively low emission maximum (490 nm) in erythrocyte membranes. Such an emission maximum is characteristic of a hydrophobic environment. DCs in PBLs also has a low emission maximum (484 nm). The lifetime of DCs in PBLs required two exponential terms to properly fit the lifetime decay curve and could not be attributed to light scattering. One short component (4.7 +/- 1.0 ns) and a second long component (18.5 +/- 1.0 ns) were resolved from the DCs fluorescence decay curves. Time-resolved anisotropy of DCs in PBLs revealed that the labeled drug was present in an anisotropic environment, consistent with at least some DCs being bound to a membrane. These fluorescence studies suggest that DCs interacts with multiple and/or heterogeneous sites in peripheral blood lymphocytes. PMID- 8471722 TI - Cholesterol is required for the fusion of single unilamellar vesicles with Mycoplasma capricolum. AB - Small unilamellar vesicles (SUV) were prepared from the total lipid extract of Mycoplasma capricolum. The SUV were labeled with the fluorescent probe octadecylrhodamine B chloride (R18) to a level at which the R18 fluorescence was self-quenched. At pH 7.4 and 37 degrees C, and in the presence of 5% polyethylene glycol, an increase in the R18 fluorescence with time was observed when the R18 labeled SUV were introduced to a native M. capricolum cell suspension. The fluorescence dequenching resulting from dilution of the R18 into the unlabeled membranes of M. capricolum, was interpreted as a result of lipid mixing during fusion between the SUV and the mycoplasma cells. The presence of cholesterol in the SUV was found to be obligatory to allow SUV-mycoplasma fusion to occur. Adaptation of M. capricolum cells to grow in a medium containing low cholesterol concentration provided cells in which the unesterified cholesterol content was as low as 17 micrograms/mg cell protein. The fusion activity of the adapted cells was very low or nonexistent. Nonetheless, when an early exponential phase culture of the adapted cells was transferred to a cholesterol-rich medium, the cells accumulated cholesterol and regained their fusogenic activity. The cholesterol requirement for fusion in the target mycoplasma membrane was met by a variety of planar sterols having a free beta-hydroxyl group, but differing in the aliphatic side chain, e.g., beta-sitosterol or ergosterol, even though these sterols, having a bulky side chain, are preferentially localized in the outer leaflet of the lipid bilayer. It is suggested that the role of cholesterol in mycoplasma-SUV fusion is not at the level of bulk bilayer viscosity but rather, affecting local lipid-lipid or lipid-protein interactions that are relevant to the fusion event. PMID- 8471723 TI - Correlation of phospholipid structure with functional effects on the nicotinic acetylcholine receptor. A modulatory role for phosphatidic acid. AB - Fourier transform infrared spectroscopy is used to characterize specific interactions between negatively charged lipids, such as phosphatidic acid, and the purified nicotinic acetylcholine receptor from Torpedo californica. The specific interaction of phosphatidic acid with acetylcholine receptor is demonstrated by the receptor-induced perturbation of the lipid ionization state, which is monitored using Fourier transform infrared bands arising from the phosphate head group. The acetylcholine receptor shifts the pKa of phosphatidic acid molecules adjacent to the receptor to a lower value by almost 2 pH units from 8.5 to 6.6. Decreased pH also leads to changes in ion channel function and to changes in the secondary structure of the acetylcholine receptor in membranes containing ionizable phospholipids. Phospholipase D restores functional activity of acetylcholine receptor reconstituted in an unfavorable environment containing phosphatidylcholine by generating phosphatidic acid. Lipids such as phosphatidic acid may serve as allosteric effectors for membrane protein function and the lipid-protein interface could be a site for activity-dependent changes that lead to modulation of synaptic efficacy. PMID- 8471724 TI - Specificity of amphiphilic anionic peptides for fusion of phospholipid vesicles. AB - We have synthesized five amphiphilic anionic peptides derived from E5 peptide [Murata, M., Takahashi, S., Kagiwada, S., Suzuki, A., Ohnishi, S. 1992. Biochemistry 31:1986-1992. E5NN and E5CC are duplications of the N-terminal and the C-terminal halves of E5, respectively, and E5CN is an inversion of the N- and the C-terminal halves. E5P contains a Pro residue in the center of E5 and E8 has 8 Glu residues and 9 Leu residues. We studied fusion of dioleoylphosphatidylcholine (DOPC) large unilamellar vesicles assayed by fluorescent probes. The peptides formed alpha-helical structure with different degrees; E5NN, E5CN, and E8 with high helical content and E5CC and E5P with low helical content. These peptides bound to DOPC vesicles at acidic pH in proportion to the helical content of peptide. The peptides caused leakage of DOPC vesicles which increased with decreasing pH. The leakage was also proportional to the helicity of peptide. Highly helical peptides E5NN, E5CN, and E8 caused hemolysis at acidic pH but not at neutral pH. The fusion activity was also dependent on the helicity of peptides. In fusion induced by an equimolar mixture of E5 analogues and K5 at neutral pH, E8, E5NN, and E5CN were most active but E5CC did not cause fusion. In fusion induced by E5-analogue peptides alone, E5CN was active at acidic pH but not at neutral pH. Other peptides did not cause fusion. Amphiphilic peptides also appear to require other factors to cause fusion. PMID- 8471725 TI - Small angle neutron scattering studies of C8 and C9 and their interactions in solution. AB - Small angle neutron scattering (SANS) results revealed that contrary to most reports C9 is not a globular protein. Its radius of gyration (Rg) at pH 8 and an ionic strength of 0.5 is 32.2 +/- 1.4 A increasing to 35 A at physiologic ionic strength. In contrast, C8, which has a 2.2-fold larger mass, has a similar Rg value [34.6 +/- 1.6 A]. Calibration plots of Rg vs. M(r) indicate that native C8 is a spherical protein whereas native C9 is elongated. From previous reports it was known that native C8 and C9 associate in solutions of low ionic strength. SANS results confirmed this observation but also demonstrated that C8-C9 heterodimers are already formed at physiologic ionic strength. The dimeric complex is globular [Rg = 40 +/- 0.8 A] indicating that the proteins associate side-by-side rather than end-to-end. In contrast, in presence of the drug Suramin, a potent inhibitor of the assembly of the C5b-9 complex, C9 forms a complex with twice the molecular mass that is still elongated (Rg = 48.8 +/- 0.8 A), suggesting that in this case the protein dimerizes end-to-end via a bridging Suramin molecule. PMID- 8471726 TI - Metal binding properties of single amino acid deletion mutants of zinc finger peptides: studies using cobalt(II) as a spectroscopic probe. AB - Peptides corresponding to Cys2His2 zinc finger domains from which one amino acid has been deleted have been synthesized and their metal-binding properties characterized. In contrast to earlier reports (Parraga, G., S. Horvath, L. Hood, E. T. Young, and R. E. Klevit. 1990. Proc. Natl. Acad. Sci. USA. 87:137-141.), such peptides do bind metal ions such as cobalt(II). A peptide with the sequence ProTyrLysCysProGluCysLysSerPheSerGlnLysSerAspLeuValLysHisGlnArgThrHis ThrGly (which corresponds to a previously characterized consensus zinc finger sequence from which a Gly residue immediately following the second Cys residue has been deleted) was found to form a 1:1 peptide to cobalt(II) complex with an absorption spectrum quite similar to those previously observed for zinc finger peptide cobalt(II) complexes. The dissociation constant for this complex is 6 x 10(-6)M, a factor of 100 times higher than that for the parent peptide. A peptide with the sequence LysProTyrProCysGlyLeuCysArgCysPheThrArgArgAspLeuLeulleArgHisAlaGln - LyslleHisSerGlyAsnLeu corresponding to a similar mutation of the peptide ADR1 was also characterized. Spectroscopic studies with cobalt(II) revealed that this peptide forms both 1:1 and 2:1 peptide to cobalt(II) complexes. The absorption spectra of the two forms and the dissociation constants were determined via deconvolution methods. In contrast, the parent peptide ADR1a was found to form only a 1:1 complex under comparable conditions and this 1:1 complex was found to be more stable than that for the mutant. These results reveal that deletion mutations do adversely affect the stability of zinc finger peptide-metal complexes but that the effects are not as drastic as had been previously described. PMID- 8471728 TI - Viral shell game. PMID- 8471727 TI - Nucleation and growth phases in the polymerization of coat and scaffolding subunits into icosahedral procapsid shells. AB - The polymerization of protein subunits into precursor shells empty of DNA is a critical process in the assembly of double-stranded DNA viruses. For the well characterized icosahedral procapsid of phage P22, coat and scaffolding protein subunits do not assemble separately but, upon mixing, copolymerize into double shelled procapsids in vitro. The polymerization reaction displays the characteristics of a nucleation limited reaction: a paucity of intermediate assembly states, a critical concentration, and kinetics displaying a lag phase. Partially formed shell intermediates were directly visualized during the growth phase by electron microscopy of the reaction mixture. The morphology of these intermediates suggests that assembly is a highly directed process. The initial rate of this reaction depends on the fifth power of the coat subunit concentration and the second or third power of the scaffolding concentration, suggesting that pentamer of coat protein and dimers or trimers of scaffolding protein, respectively, participate in the rate-limiting step. PMID- 8471729 TI - Theory of photoselection by intense light pulses. Influence of reorientational dynamics and chemical kinetics on absorbance measurements. AB - The theory of absorbance measurements on a system (e.g., chromophore(s) in a protein) that undergoes a sequence of reactions initiated by a linearly polarized light pulse is developed for excitation pulses of arbitrary intensity. This formalism is based on a set of master equations describing the time evolution of the orientational distribution function of the various species resulting from excitation, reorientational dynamics, and chemical kinetics. For intense but short excitation pulses, the changes in absorbance (for arbitrary polarization directions of the excitation and probe pulses) and the absorption anisotropy are expressed in terms of reorientational correlation functions. The influence of the internal motions of the chromophore as well as the overall motions of the molecules is considered. When the duration of the excitation pulse is long compared to the time-scale of internal motions but comparable to the overall correlation time of the molecule that is reorienting isotropically, the problem of calculating the changes in absorbance is reduced to the solution of a set of first-order coupled differential equations. Emphasis is placed on obtaining explicit results for quantities that are measured in photolysis and fluorescence experiments so as to facilitate the analysis of experimental data. PMID- 8471730 TI - Photoselection in polarized photolysis experiments on heme proteins. AB - Polarized photolysis experiments have been performed on the carbon monoxide complex of myoglobin to assess the effects of photoselection on the kinetics of ligand rebinding and to investigate the reorientational dynamics of the heme plane. The results are analyzed in terms of the optical theory developed in the preceding paper by Ansari and Szabo. Changes in optical density arising from rotational diffusion of the photoselected population produce large deviations from the true geminate ligand rebinding curves if measurements are made with only a single polarization. The apparent ligand rebinding curves are significantly distorted even at photolysis levels greater than 90%. These deviations are eliminated by obtaining isotropically-averaged optical densities from measurements using both parallel and perpendicular polarizations of the probe pulse. These experiments also yield the optical anisotropy, which gives a novel method for accurately determining the degree of photolysis, as well as important information on the reorientational dynamics of the heme plane. The correlation time for the overall rotational diffusion of the molecule is obtained from the decay of the anisotropy. The anisotropy prior to rotational diffusion is lower than that predicted for a rigidly attached, perfectly circular absorber, corresponding to an apparent order parameter of S = 0.95 +/- 0.02. Polarized absorption data on single crystals suggest that the decreased anisotropy results more from internal motions of the heme plane which take place on time scales shorter than the duration of the laser pulse (10 ns) than from out-of-plane polarized transitions. PMID- 8471731 TI - Molecular dynamics simulations of heme reorientational motions in myoglobin. AB - Molecular dynamics simulations of 2-ns duration were performed on carbonmonoxymyoglobin and deoxymyoglobin in vacuo to study the reorientational dynamics of the heme group. The heme in both simulations undergoes reorientations of approximately 5 degrees amplitude on a subpicosecond time scale, which produce a rapid initial decay in the reorientational correlation function to about 0.99. The heme also experiences infrequent changes in average orientation of approximately 10 degrees amplitude, which lead to a larger slow decay of the reorientational correlation function over a period of hundreds of picoseconds. The simulations have not converged with respect to these infrequent transitions. However, an estimate of the order parameter for rapid internal motions of the heme from those orientations which are sampled by the simulations suggests that the subnanosecond orientational dynamics of the heme accounts for at least 30% of the unresolved initial anisotropy decay observed in the nanosecond time-resolved optical absorption experiments on myoglobin reported by Ansari et al. in a companion paper (Ansari, A., C.M. Jones, E.R. Henry, J. Hofrichter, and W.A. Eaton. 1992. Biophys. J. 64:852-868.). A more complete sampling of the accessible heme orientations would most likely increase this fraction further. The simulation of the liganded molecule also suggests that the conformational dynamics of the CO ligand may contribute significantly to discrepancies between the ligand conformation as probed by x-ray diffraction and by infrared-optical photoselection experiments. The protein back-bone explores multiple conformations during the simulations, with the largest structural changes appearing in the E and F helices, which are in contact with the heme. The variations in the heme orientation correlate with the conformational dynamics of the protein on a time scale of hundreds of picoseconds, suggesting that the heme orientation may provide a useful probe of dynamical processes in the protein. PMID- 8471732 TI - Analysis of ordered arrays of adsorbed lysozyme by scanning tunneling microscopy. AB - Scanning tunneling microscopy (STM) has been used to observe lysozyme at a graphite surface directly in order to gain mechanistic information about the molecular events involved in protein adsorption. The experiments were performed using an insulated tip in an aqueous protein solution, allowing the time course of the adsorption process to be followed, including the evolution of ordered arrays. Ordered arrays of protein molecules were observed, with lattice spacings that varied with bulk protein concentration and salt strength. Fourier analysis was used to determine the average cell dimensions of an array. From the observed lattice spacings, it was possible to estimate the surface coverage of the protein, and thus, by varying the conditions, adsorption isotherms could be obtained. These isotherms compare well with adsorption isotherms measured using total internal reflectance fluorescence (TIRF) spectroscopy on a hydrophobic surface. Since the protein is charged and the electrolyte has an effect on the isotherms, electrostatics are a likely controlling factor. Molecular electrostatics computations were thus used to investigate the possible origins of the lattice structure, and they suggest that favorable intermolecular interactions among adsorbed molecules are consistent with hydrophobically dominated protein-surface interactions. PMID- 8471733 TI - Aggregation of hapten-bearing liposomes mediated by specific antibodies. AB - We studied specific membrane-membrane interactions mediated by ligand-receptor binding in a model system, which consisted of (a) FG3P, the fluorescein hapten attached to a phospholipid by a peptidyl spacer as described previously (Petrossian, A., A.B. Kantor, and J.C. Owicki. 1985. J. Lipid Res. 26:767-773), (b) antifluorescein monoclonal antibodies (MAbs), and (c) phospholipid vesicles (liposomes) into which the FG3P was incorporated. The aggregation of the hapten bearing liposomes by four MAbs was studied by differential centrifugation. The ability of the MAbs to induce vesicle aggregation varied considerably and correlated inversely with affinity. Aggregation by one of the MAbs was studied in more detail by turbidimetry and freeze-fracture electron microscopy of samples frozen throughout the course of the aggregation. Rapid freezing was achieved with a double propane-jet apparatus. The aggregate morphologies and the time evolution of the aggregate size distribution were obtained from the two-dimensional fracture views with a stereological correction. The aggregation kinetics were simulated by considering dynamical aggregation according to a mass-action model with two parameters, the rate constants for antibody-mediated vesicle aggregation and disaggregation. Both rate constants were orders of magnitude lower than the rate constants for the corresponding interactions of antibodies with haptens either in solution or on vesicles under nonaggregating conditions. PMID- 8471734 TI - A COOH-terminal peptide confers regiospecific orientation and facilitates atomic force microscopy of an IgG1. AB - An antibody (IgG1) was designed for oriented adherence to a metal-containing surface. This was achieved by adding a metal-chelating peptide, (CP = His-Trp-His His-His-Pro), to the COOH-terminus of the heavy chain through genetic engineering. Electroporation of the engineered heavy chain gene into cells expressing the complimentary light chain yielded colonies secreting an intact antibody containing the metal-chelating peptide (IgG1-CP) which had high affinity for a nickel-loaded iminodiacetate column. Purified IgG1-CP was bound to nickel treated mica and imaged by atomic force microscopy (AFM). Antibody lacking the COOH-terminal metal binding peptide failed to produce discernible AFM images. The AFM images of individual IgG1-CP molecules and their calculated dimensions demonstrated that regiospecific binding and uniform orientation of the antibody was imparted by the peptide. The ability to stably orient macromolecules in their native state to a surface may be used advantageously to visualize them. PMID- 8471735 TI - Study of the torque of the bacterial flagellar motor using a rotating electric field. AB - Bacterial flagella are driven by a rotary motor that is energized by an electrochemical ion gradient across the cell membrane. In this study the torque generated by the flagellar motor was measured in tethered cells of a smooth swimming Escherichia coli strain by using rotating electric fields to determine the relationship between the torque and speed over a wide range. By measuring the electric current applied to the sample cell and combining the data obtained at different viscosities, the torque of the flagellar motor was estimated up to 55 Hz, and also at negative rotation rates. By this method we have found that the torque of the flagellar motor linearly decreases with rotation rate from negative through positive rate of rotation. In addition, the dependence of torque upon temperature was also investigated. We showed that torque at the high speeds encountered in swimming cells had a much steeper dependence on temperature that at the low speeds encountered in tethered cells. From these results, the activation energy of the proton transfer reaction in the torque-generating unit was calculated to be about 7.0 x 10(-20) J. PMID- 8471736 TI - Cardiovascular effects of capsaicin-sensitive neurons. AB - Calcitonin gene-related peptide, the main transmitter released from capsaicin sensitive sensory-motor fibers, has positive inotropic and chronotropic effects on the heart and causes vasodilatation in the coronary arteries and elsewhere in the peripheral vasculature. We review some aspects of the cardiovascular actions induced by exogenous calcitonin gene-related peptide and by release of the peptide following activation of capsaicin-sensitive nerves. The efferent function of cardiac sensory-motor neurones is modulated by a number of endogenous substances of physiopathological interest, including opioid peptides, norepinephrine and adenosine. The receptors involved in the prejunctional regulation due to these substances have been characterized. Studies on the mesenteric bed of the rat have shown that, at least in such a resistance vascular bed, the relaxing effect of calcitonin gene-related peptide is mediated by a direct mechanism independent of endothelium-derived nitric oxide release. In cultured human endothelial cells from the umbilical cord vein, calcitonin gene related peptide, at nM concentrations, stimulates cell growth in a dose-dependent manner. The possible implications of calcitonin gene-related peptide in the physio-pathological regulation of the cardiovascular system and in the trophism of vascular tissues are discussed. PMID- 8471737 TI - Increased nuclear proto-oncogene expression in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy is characterized by an unexplained hypertrophy of the left ventricle, particularly the interventricular septum. Although point mutations in the beta-myosin chain gene have been found in several US families in familiar hypertrophic cardiomyopathy, the pathogenetic pathways leading to myocyte hypertrophy, the most important feature, are still not clear. To examine whether activation (expression) of nuclear proto-oncogenes may play a role in hypertrophic cardiomyopathy, endomyocardial biopsies from 13 patients with hypertrophic cardiomyopathy were examined using monoclonal antibodies against c myc, c-fos and c-jun. The nuclear proto-oncogenes c-fos, c-jun and c-myc were expressed in 53, 60, and 50%, respectively, of patients with hypertrophic cardiomyopathy. In control biopsies, c-myc was detectable in only 10% of the patients, while c-fos and c-jun were always undetectable. These results show that nuclear proto-oncogenes are induced in patients with hypertrophic cardiomyopathy, although the triggering mechanisms remain unknown. PMID- 8471738 TI - Prodynorphin mRNA is synthesized in adult cultured rat ventricular cardiomyocytes. AB - In the myocardial cell, stimulation of the K opioid receptor is involved in the modulation of cytosolic calcium and pH homeostasis, as well as in the regulation of myofilament responsiveness to calcium. In the present study, we found that prodynorphin mRNA, which encodes for the synthesis of a common precursor of opioid peptides interacting with K sites, is synthesized both in atrial and ventricular tissue of the rat heart. In adult cultured rat ventricular cardiomyocytes, the level of prodynorphin mRNA did not differ from that detected in the original ventricular tissue. This finding indicates that the myocardial cell is a source for prodynorphin gene expression and has the potential for an intrinsic synthesis of dynorphin-related peptides. PMID- 8471739 TI - Myocardial xanthine oxidoreductase activity in hypertensive and hypercholesterolemic rats. AB - In several species, xanthine oxidoreductase activity seems to be a major source of free radicals in myocardial tissue. Its activity changes during development and aging, at least in the rat heart. Hardly any data are available about its activity in two important diseases, hypertension and hypercholesterolemia, in which the production of free radicals induced by xanthine oxidoreductase activity could play a role. Therefore we measured the activity of xanthine oxidase and dehydrogenase in myocardial tissue of spontaneously hypertensive. Wistar (control hypertensive), Yoshida (hypercholesterolemic) and Brown Norway (control hypercholesterolemic) rats of various ages. Cytosolic fractions were incubated at 30 degrees C, pH 8.3, with 60 microM xanthine, and the formation of urate was measured with high performance liquid chromatography. In the Wistar group, xanthine oxidoreductase activity was relatively constant during aging (about 1.8 U/g protein). In the hypertensive group, the activity increased gradually from 1.7 to 2.3 U/g at 18 months (p < 0.05 compared with Wistar at 18 months). Xanthine oxidase was about twice as high in both groups at 18 months (p < 0.001 compared with 2 and 6 months). The ratio of xanthine dehydrogenase to xanthine oxidase had decreased 42% at this age (p < 0.001). In the Yoshida and Brown Norway groups, xanthine oxidoreductase activity was similar, with a peak at 6 months. These data suggest that the hypercholesterolemic state does not influence xanthine oxidoreductase activity. In contrast, in hypertrophied myocardium, xanthine oxidoreductase activity was higher than in the control, suggesting a different potential for free-radical generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471740 TI - Low frequency oscillations in pulmonary arterial pressure in chronic heart failure. AB - Spontaneous, sustained low frequency oscillations of pulmonary arterial pressure were observed in 8 patients with moderate to severe chronic heart failure during recordings of pulmonary arterial pressure of 8.6 to 48 hours duration. The oscillations (frequency range 0.015 to 0.035 Hz) had a distinct peak from and lower frequency range than respiration (0.2 to 0.6 Hz) and heart rate (0.8 to 1.9 Hz). They were present from 42% to 82% of the recording time with an amplitude varying from undetectable to a maximum range from 5.3 mm Hg to 19.7 mm Hg. When detectable, the mean amplitude of the low frequency oscillations of pulmonary arterial pressure ranged from 1.2 +/- 1.2(SD) mm Hg to 4.3 +/- 3.3 mm Hg. These oscillations are lower in frequency than the low frequency component usually described in recordings of systemic arterial pressure and heart rate in normal subjects, and are closer to the very low frequency rhythms described in severe chronic heart failure and Cheyne Stokes respiration. PMID- 8471741 TI - Influence of atherosclerosis on the vascular reactivity of isolated human epicardial coronary arteries to leukotriene C4. AB - Leukotrienes, lipid mediators derived from arachidonic acid by the 5-lipoxygenase pathway, have been implicated in a variety of myocardial ischemic events including myocardial infarction and coronary spasm. We have examined the comparative effects of leukotriene C4 in isolated human non-atherosclerotic and atherosclerotic coronary arteries to gain an insight into the role of leukotrienes in coronary heart disease. Human coronary arteries, obtained from recipient hearts at the time of cardiac transplantation, were cut into rings and examined in an isolated organ bath. In atherosclerotic arteries leukotriene C4 (1nM-100nM) produced a maximal contractile response of 54.9 +/- 7.98% KCI (n = 7) and the mean EC50 value was 11.1nM (95% confidence interval: 9.4-13.0). The leukotriene receptor antagonist ICI-198,615 (3 x 10(-8)M) produced an approximate 50-fold rightward shift of the leukotriene C4 dose-response curve (n = 5). In contrast, non-atherosclerotic arteries were either non-responsive (n = 5) or only weakly responsive (n = 2) to leukotriene C4 (1nM-100nM), producing an average maximum response of 3.65 +/- 3.05% KCI (n = 7; p < 0.01 atherosclerotic vs non atherosclerotic). In the presence of indomethacin and in vessels denuded of endothelium, non-atherosclerotic arteries remained unresponsive to leukotriene C4 (n = 3). In addition, leukotriene C4 did not relax preconstricted vessels (n = 7). In vitro autoradiography showed specific [3H]-leukotriene C4 binding to smooth muscle in both non-atherosclerotic and atherosclerotic arteries, with no evidence of endothelium-dependent binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471742 TI - Modulation of parasympathetic and baroreceptor control of heart rate. AB - The heart rate is modulated from beat to beat by efferent vagal and sympathetic fibers, the former being the predominant mediators of the chronotropic influence of arterial baroreceptors and respiration and the latter being important in the cardiac responses to physical and mental stress. Cardiac vagal influences are modulated by a number of factors. These can be grouped as: 1) neural factors, such as the wakefulness-sleep cycle, the alerting reaction, and exercise; 2) humoral-pharmacological factors, such as angiotensin II, atrial natriuretic factor, cardiac glycosides; 3) normal aging; 4) a number of cardiovascular and other diseases, such as arterial hypertension, coronary artery disease, congestive heart failure and diabetes mellitus. The mechanisms underlying modulation of cardiac vagal control are not completely understood, the range of the possibilities including structural or functional alterations in baroreceptor afferents, in central and efferent vagal pathways and in cardiac responsiveness to neural stimuli. Irrespective of the mechanisms involved, the modulation of cardiac vagal control may have important implications for normal cardiovascular homeostasis, as well as for the pathophysiology, diagnosis and prognosis of various diseases. PMID- 8471743 TI - Use of amrinone in cardiac surgery patients. PMID- 8471744 TI - Pharmacologic and mechanical methods of discontinuing extracorporeal circulation in patients with heart failure. AB - Separation from EC requires simultaneous optimal manipulation of heart rate and rhythm, loading conditions, afterload, and contractility. Patients with preexisting ventricular dysfunction will have alterations in beta-adrenergic receptors and responsiveness to catecholamines, but patients with previously normal ventricular function can also develop ventricular dysfunction. Catecholamines, by stimulating beta-adrenergic receptors, decrease systolic function to allow separation from EC. The phosphodiesterase inhibitors provide both inotropic support and vasodilation, to improve both systolic and diastolic function. When administered in combination, catecholamines and cyclic-AMP specific phosphodiesterase inhibitors can have additive effects to restore beta 1 adrenergic responsiveness. Combination therapy provides an important support during biventricular dysfunction and facilitates separation from EC. Finally, mechanical support provides a therapeutic option when pharmacologic therapy is ineffective. PMID- 8471745 TI - Diastolic dysfunction in post-cardiac surgical management. AB - Although an appropriate definition of primary diastolic failure is still not at hand, primary diastolic failure is a distinct pathophysiologic syndrome. It is due to an increased resistance to ventricular filling and results in an inappropriate upward shift of the diastolic P-V relationship, especially during exercise. This leads to exercise intolerance with symptoms of congestion. The causes are known, ie, impaired systolic relaxation, decreased diastolic compliance, and inappropriate tachycardia. Pathophysiologically impaired (incomplete or slowed) systolic relaxation must be distinguished from physiologic, compensatory prolonged contraction (delayed or retarded relaxation). Treatment of diastolic failure is feasible, but necessitates a clear understanding of the etiology, pathogenesis, and pathophysiology of the underlying cardiac disease. Optimal therapy will depend on the type of disease, on the phase during the pathophysiologic evolution of a given disease, and on the coexistence and relative contribution of various compensatory or decompensatory mechanisms. This often requires a comprehensive analysis of hemodynamics, for example, with echo-doppler, completed, whenever necessary, by catheterization. PMID- 8471746 TI - Milrinone and postoperative pulmonary hypertension. PMID- 8471747 TI - Post-cardiac surgery pulmonary hypertension. PMID- 8471748 TI - The role of luminal factors in prostaglandin protection against ethanol-induced gastric mucosal injury. AB - Prostaglandins (PG) protect the gastric mucosa against damage by several irritants, but the mechanisms remain unclear. A standard rat model of gastric injury induced by 50% ethanol was used to test the hypothesis that PG protection occurs either by increasing luminal fluid volume and hence diluting the irritant, or by production of protective factors within this fluid. Quantitative histology was used to assess microscopic mucosal damage. The increase in luminal fluid volume in prostaglandin E2 (PGE2)-treated animals was measured, and the ability of this increased fluid to protect saline-treated animals via dilution of the irritant was assessed. The transfer of protection by exchange of luminal fluid from PG to non-PG treated animals was also tested. Results showed that PGE2 induced a specific increase in luminal fluid volume of 45.6%. When given together with ethanol treatment the extra fluid volume was not protective. Removal of luminal fluid after PG and before ethanol treatment did not abolish protection and no protective factor was transferred with the luminal fluid. In conclusion, this study has shown that neither dilution of ethanol by accumulation of luminal fluid nor the presence of luminal factors is responsible for PG protection. PMID- 8471749 TI - High prevalence of duodenal ulcer in Indochinese immigrants attending an Australian university hospital. AB - Indochinese migrants to Australia appear to have a high prevalence of duodenal ulcer (DU). To examine this hypothesis a 2 year audit of the prevalence of symptomatic DU among patients attending a general hospital was conducted. The last 6 months of this period included a prospective assessment of ulcer risk factors. In Australian-born patients DU prevalence was 8.4 per 1000 admissions. By comparison, prevalence in Indochinese was 24.6 per 1000 admissions (P < 0.001) with an age standardized prevalence of 30.3 per 1000 (P < 0.001). This represented a relative risk in Indochinese of 2.9 using crude data and 3.6 after age standardization. The increased risk was demonstrated only in males: very few DU were diagnosed in female Indochinese. Ulcer prevalence increased in Indochinese for each age decile between 10 and 80 years, with statistical significance (P < 0.01) reached in the age brackets 0-19, 20-39 and 60-79 years. Ulcer prevalence was also increased in some other ethnic groups. However, when referral bias was taken into account (by calculating the ratio of endoscopies to total admissions for each group), a significant increase in DU prevalence could only be confidently demonstrated in Indochinese. Analysis of risk factors showed that among DU patients, Indochinese were significantly less likely to smoke (P < 0.05) and also had a tendency to ingest less non-steroidal anti-inflammatory drugs (NSAID) and to consume less alcohol. PMID- 8471750 TI - Diagnosis of gastric adenoma versus early gastric cancer by bromodeoxyuridine immunohistochemistry from gastric biopsy specimen. AB - Differentiation between gastric adenomas and type IIa early gastric cancer by macroscopic and histologic examinations is often difficult. This study has shown that there are differences in the distribution of S-phase cells in these two types of tumour, and these differences can be exploited to differentiate between them. The distribution of S-phase cells was assessed by Bromodeoxyuridine (BrdU) immunohistochemistry using an in vitro BrdU-labelling method. Biopsy specimens were obtained from 27 lesions (12 adenomas and 15 type IIa early gastric cancers), and the distributions of BrdU-labelled cells in the tumour thickness as well as in the superficial layer of the tumour were determined. Significant difference was seen in the labelling of the two tumour types with regard to both these parameters. Using the criteria of BrdU immunohistochemistry, the accuracy of differentiation between gastric adenomas and cancers was 88.9%. Therefore, it is concluded in this study that in vitro BrdU labelling is a useful method of diagnosing gastric adenomas and cancers. PMID- 8471751 TI - Biliary bile acids in the gall-bladder and the common bile duct of patients with anomalous pancreaticobiliary ductal junction. AB - The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) with or without choledochal cyst (CC) has been well documented. Twenty-two patients with APBDJ were divided into three groups: Group A, four patients not associated with CC and biliary tract carcinoma; Group B, 13 patients with CC but without biliary tract carcinoma; and Group C, five patients with biliary tract carcinoma (four with and one without CC). Profiles of bile acids in the gall-bladder and/or common bile duct were analysed in these patients and compared with those in the control patients with cholecystlithiasis to examine the hypothesis that the levels of deoxycholic acid (DCA) and lithocholic acid (LCA) are elevated in patients with APBDJ because these secondary bile acids are mutagenic. Bile acids were quantified by gas liquid chromatography. Total bile acid concentration in the gall-bladder bile was significantly lower in any group with APBDJ than that of controls. In the gall bladder, increased proportion of chenodeoxycholic acid (CDCA) in Group A and B, decreased proportion of DCA in Group B and increased proportion of cholic acid (CA) in Group C were found in bile. In the bile duct, total bile acid concentration and proportion of DCA were significantly low in bile from Group C and decreased proportion of DCA and increased proportion of CDCA were found in bile from Group B. In both the gall-bladder and hepatic bile, proportion of LCA was not significantly different between any intergroups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471752 TI - Prevalence of primary sclerosing cholangitis and other liver diseases in Japanese patients with chronic ulcerative colitis. AB - An association between primary sclerosing cholangitis (PSC) and chronic ulcerative colitis (CUC) is well known in Western countries, but there have been no reports on this association in Japan. We reviewed 163 consecutive CUC patients (91 males and 72 females) diagnosed from 1984 to 1990 at Tokyo Women's Medical College. Abnormal liver function tests were found in 42 patients with CUC (25.8%), but chronic liver disease was only diagnosed in seven patients (4.3%). Among these seven patients, there were four with PSC, one with small-duct PSC, one with transfusion-associated chronic hepatitis and one with Type B liver cirrhosis. No relationship was found between the documented colonic manifestations of CUC and the presence of PSC. The four PSC patients did not have a longer history of CUC at the time of diagnosis of PSC than CUC patients without PSC. At the time of PSC diagnosis, two patients were asymptomatic, one presented with right upper quadrant pain, and the other had fatigue. Three patients were diagnosed as having CUC before the onset of PSC (range 2-13 years), and the other patient had both diseases simultaneously. All four had a good prognosis. Thus PSC was the most common chronic liver disease associated with CUC in our series, and it was present in all our CUC patients with alkaline phosphatase levels exceeding twice the upper limit of normal and mild transaminase elevation. PMID- 8471753 TI - Measurement of intravariceal pressure by fine needle direct puncture in hepatitis B surface antigen-positive cirrhotic patients: the effect of vasopressin. AB - The pressure of oesophageal varices was determined by fine needle direct puncture in 19 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis after the first episode of variceal bleeding before endoscopic sclerotherapy. Both the stability and reliability of the measurement of intravariceal pressure by fine needle puncture were confirmed. Seven patients received intravenous 1 mL normal saline. Intravariceal pressure did not change before and after injection of normal saline (16.3 +/- 4.0 vs 16.0 +/- 4.0 mmHg, P > 0.05). Twelve patients received intravenous 1 units vasopressin and this caused a significant reduction in intravariceal pressure (15.6 +/- 2.6 vs 10.3 +/- 2.9 mmHg, P < 0.0001). The average basal intravariceal pressure in these patients was 15.8 +/- 3.1 mmHg. After intravariceal pressure was recorded, the needle was left in situ and endoscopic sclerotherapy commenced immediately. During the investigation, no adverse reaction or complication was encountered. It was concluded that the measurement of intravariceal pressure by fine needle direct puncture followed by immediate sclerotherapy is a safe and simple method to evaluate the short-term effect of drug prevention from oesophageal variceal bleeding and that vasopressin causes reduction of intravariceal pressure. PMID- 8471754 TI - Extrahepatic portal vein obstruction in adults detected by ultrasound with frequent lack of portal hypertension signs. AB - Extrahepatic portal vein obstruction (EHPO) was seen in 54 adult patients at the Chiba University Hospital and affiliated hospitals from 1978 to 1991. They were classified according to the background disease (Group A, unknown aetiology; Group B, benign disease; Group C, malignant disease). Among the initial symptoms and signs, abdominal pain was the most frequent in Group A (37%), and symptoms attributable to the primary disease in Groups B (44%) and C (75%). Definite or probable diagnosis was made in 45 of the 54 patients (81.8%) by ultrasound (US) examination carried out because of these symptoms and signs. Signs of portal hypertension were observed in 67% of patients; oesophageal varices were seen in 60%. Extrahepatic portal vein obstruction without portal hypertension signs was characterized by thick extensive hepatopetal collaterals or patency of some intrahepatic portal veins. Extrahepatic portal vein obstruction patients without portal hypertension remained free of its signs for more than 3 years of follow up and, in fact, EHPO without portal hypertension signs was a common occurrence. Emphasis is made on the diagnostic value of US examination which was useful in identifying the relation of clinical manifestation of EHPO to pathophysiology, and on the frequent lack of portal hypertension signs in this disease. PMID- 8471755 TI - Pruritus and cholestasis: therapeutic options. AB - The pathogenesis of pruritus of cholestasis remains unclear. Bile salts do not appear to be the sole prurogens in cholestasis. Histaminergic pathways may be involved, and central opiate receptor processes seem much more important than has previously been recognized. The therapeutic options for relief of cholestatic pruritus are summarized in Table 2. Resins such as cholestyramine are the first line of therapy. In cases where cholestyramine has failed, rifampicin and antihistamines may be beneficial. Opiate antagonists hold great potential if opioid withdrawal-like syndromes can be avoided. Ursodeoxycholic acid and methotrexate have an advantage in not only relieving pruritus but also potentially retarding disease progression in PBC and PSC, respectively, although this remains to be proved. Other agents such as EPO and SAMe remain experimental and require further study to clarify their effectiveness before they can be recommended. PMID- 8471756 TI - Tumour suppressor genes and colorectal neoplasia. AB - Two distinct gene classes have been implicated in colorectal carcinogenesis. Tumour promoter genes (oncogenes, dominant oncogenes) produce an excessive positive stimulus to cell proliferation. The ras family of oncogenes are an example. Acquired mutations of the c-k-ras gene are commonly found in colonic adenomas and carcinomas. Tumour suppressor genes (anti-oncogenes, recessive oncogenes) normally constrain or regulate cell proliferation. Loss of this function through gene deletion or mutation is oncogenic. Inherited tumour suppressor gene mutations have now been identified in several of the familial cancer syndromes. Acquired tumour suppressor gene mutations are found in both sporadic and hereditary cancers. Together with the tumour promoter genes they provide the genetic basis for the cellular changes occurring during carcinogenesis. The retinoblastoma gene was the first human tumour suppressor gene to be characterized and exemplifies the class. More recently, linkage studies in the hereditary cancer syndromes and the detection of specific deletions in sporadic tumours have helped to identify several new tumour suppressor genes. At least four of these (MCC, APC, p53 and DCC) apparently contribute to sporadic colorectal carcinogenesis. Germ line APC mutations produce the inherited colorectal cancer syndrome familial adenomatous polyposis (FAP). Detection of these mutations using linked markers has already found clinical application in the screening of families with this disease. In the future, genetic diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) and the recognition of those genetically susceptible to sporadic colorectal cancer may become possible. At the same time, as our understanding of the genes involved improves, new avenues for treatment and prevention of colorectal cancer may emerge. PMID- 8471757 TI - Selection of patients for liver transplantation. AB - Liver transplantation is now available world-wide. It plays an important role in the treatment of irreversible acute and chronic liver disease (CLD). Selection of patients for liver transplantation is subject to many factors including economic, cultural, availability of donor organs and degree of illness. This article looks at seven general considerations for recipients of liver transplantation. As well, disease-specific criteria are investigated and include such areas as cirrhosis due to chronic hepatitis B virus (HBV), hepatitis C virus (HCV) positive cirrhosis, fulminant hepatic failure (FHF), malignancy, alcoholic liver disease (ALD), metabolic conditions and Budd-Chiari syndrome. If hepatic transplantation survival rates were to approach 95%, the relative risk ratio between transplantation and conservative therapy would increase. At present an 80% 1-5 year survival rate following transplantation should be expected. PMID- 8471758 TI - Hepatic-pericardio-phrenic collateral (natural shunt) in a patient with Budd Chiari syndrome. AB - Hepatic venous outflow tract obstruction, Budd-Chiari syndrome (BCS), leads to portal hypertension and to the development of collaterals that bypass the obstruction. Described here is a BCS patient with an unusually large transdiaphragmatic collateral between the left hepatic and left innominate veins, which decompressed the oesophageal varices. This has not been reported earlier in the literature. PMID- 8471759 TI - Detecting genetic changes in human tumor cells: have scientists "gone fishing?". PMID- 8471760 TI - Autoimmune neutropenia. AB - There have been several new developments in the field of autoimmune neutropenia over the past decade. Neutropenia caused by antibodies directed against granulocyte precursor cells, the oligoclonal nature of antineutrophil antibodies, and the expanding knowledge of neutrophil antigens, particularly in relationship to autoantibodies, are exciting new areas of investigation. Knowledge has also been advanced in the effector mechanisms of neutrophil autoantibodies and the effect of autoantibodies on the neutrophil function. In addition, some clinical syndromes of immune neutropenia have been better defined over the past decade, such as autoimmune neutropenia of infancy and chronic idiopathic neutropenia in adults. The past decade also saw interesting developments in the treatment of immune neutropenia, particularly in the use of gammaglobulin preparations and more recently in the advent of hematopoietic growth factors. This review focuses on these newer aspects of autoimmune neutropenia. PMID- 8471761 TI - Antineutrophil cytoplasmic autoantibodies: a review of the antigens involved, the assays, and the clinical and possible pathogenetic consequences. PMID- 8471762 TI - Curability of relapsed childhood B-cell non-Hodgkin's lymphoma after intensive first line therapy: a report from the Societe Francaise d'Oncologie Pediatrique. AB - The very high cure rate in advanced B-cell non-Hodgkin's lymphoma in children using intensive multiagent therapy has been previously reported by the French Societe Francaise d'Oncologie Pediatrique lymphoma Malin B type (LMB) group. To address the issue of salvageability in an unselected group of patients who had all received the same front-line therapy, the outcome of relapses following the LMB 84 (216 patients) protocol have been reviewed. Fourteen percent of patients achieving complete remission (CR) relapsed, ie, 27 of 195. Relapse sites comprised the central nervous system (CNS) alone (6 cases), lung or mediastinum (2 cases), abdomen (8 cases), head and neck (2 cases), or multifocal (9 cases). There were three early deaths due to disease. Twenty-four patients received rescue chemotherapy regimens and 15 were treated with high-dose chemotherapy and bone marrow rescue (1 allogeneic). Of these, 9 were in second CR, 4 in second partial remission, and 2 treated during progressive disease. One died in CR from treatment-related toxicity. Ten relapsed postbone marrow transplant and 4 are alive disease free and probably cured. Two of the long-term survivors had some delay during initial chemotherapy due to toxicity and two were isolated CNS relapses. Twelve of 27 patients did not proceed to megatherapy (12 of 12 died). PMID- 8471763 TI - Initial assessment of the beneficial effect of partial splenectomy in hereditary spherocytosis. AB - Clinical manifestations of hereditary spherocytosis (HS), the most common red blood cell (RBC) membrane disorder, can be abrogated or markedly reduced by splenectomy. However, concerns regarding risks from overwhelming infections after splenectomy have restricted its use, especially in children. This study was designed to determine if partial splenectomy can decrease the hemolytic rate while maintaining phagocytic function of the spleen. Partial splenectomy was performed in 11 children (age 2 to 13) with HS. The effect on hemolytic rate was assessed by comparing the presurgical and postsurgical values for hemoglobin, reticulocyte number, and RBC life span. The residual splenic phagocytic function was assessed using technetium 99m scans and by enumerating the percentage of pitted RBCs in circulation. There were no complications from the surgical procedure in any of the 11 individuals. Following partial splenectomy, hemoglobin increased on the average by 3 g/dL, reticulocyte count decreased by 300 x 10(6)/L, and RBC life span was substantially prolonged. Normal technetium uptake was noted in the splenic remnant and the percentage of pitted RBCs was in the normal range. Partial splenectomy is effective in decreasing the hemolytic rate while maintaining residual splenic phagocytic function of the spleen in HS. We conclude that the use of this procedure as treatment for RBC membrane disorders warrants consideration, especially in infants under 5 years of age who need frequent transfusions. PMID- 8471764 TI - Immune reconstitution in severe combined immunodeficiency disease after lectin treated, T-cell-depleted haplocompatible bone marrow transplantation. AB - We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus-host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor. PMID- 8471765 TI - Glanzmann's thrombasthenia caused by homozygosity for a splice defect that leads to deletion of the first coding exon of the glycoprotein IIIa mRNA. AB - Glanzmann's thrombasthenia (GT) is the result of the absence or of an altered and dysfunctional expression on the platelet membrane of the fibrinogen receptor (glycoprotein [GP] IIb/IIIa complex). Various molecular genetic mechanisms have been found to be responsible for this inherited disease. In a patient with a severe type of GT, we have found a splice variant in the GP IIIa gene that leads to premature chain termination. Immunoprecipitation experiments, using monoclonal antibodies specific for GP IIb/IIIa, showed that GP IIb/IIIa was not detectable on the platelet membrane. Amplification of reversely transcribed platelet GP IIIa mRNA by the polymerase chain reaction and subsequent sequence analysis showed a 86-bp deletion, which corresponds to exon i of the GP IIIa gene. This deletion results in a shift of the reading frame leading to eight altered amino acids followed by a premature termination codon. Analysis of the corresponding genomic DNA fragments showed three mutations in the exon i-intron i boundary region of the GP IIIa gene. One of these mutations is a G-->T transition that eliminates the GT splice donor site in the wild type. This base pair change creates a restriction site for the enzyme Mse I. Allele-specific restriction enzyme analysis (ASRA) with Mse I of amplified genomic DNA of the parents and the proposita showed that both parents (who are first cousins) are heterozygous, whereas the proposita is homozygous for the G-->T substitution. PMID- 8471767 TI - Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus. AB - Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy. PMID- 8471766 TI - Active site-blocked factor Xa prevents thrombus formation in the coronary vasculature in parallel with inhibition of extravascular coagulation in a canine thrombosis model. AB - Factor Xa is a central procoagulant enzyme, linking the intrinsic and extrinsic activation mechanisms to the final common pathway of coagulation. To assess its contribution to pathologic thrombosis, studies were performed in a canine coronary thrombosis model. Thrombus formation was initiated by the application of electric current via a needle electrode placed in the lumen of the left circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycinyl-arginyl-factor Xa (Xai), a competitive inhibitor of factor Xa assembly into the prothrombinase complex, Factor X, or heparin. Animals infused with saline or factor X (300 micrograms/kg) developed total occlusion of the vessel due to a fibrin/platelet thrombus in 70 +/- 11 minutes (36 of 36 animals) and 74 +/- 13 minutes (8 of 8 animals), respectively. In contrast, infusion of Xai prevented thrombus formation completely at a dose of 300 micrograms/kg (8 of 8 animals). As the dose of Xai was decreased, its antithrombotic effect was diminished, with a patency rate of only 2 of 6 animals at a dose of 90 micrograms/kg. Xai at 300 micrograms/kg prevented the accumulation of 125I-fibrinogen/fibrin at the site of the coronary thrombus by approximately 63% and decreased deposition of 111In-labeled platelets by approximately 57%. Hemostatic parameters of animals infused with Xai demonstrated prolongation of the PT and dose-dependent increased extravascular bleeding tendency. These data indicate that factor Xa has a comparably important role in thrombus formation and extravascular hemostasis, and contrast with previous results in this same animal model in which IXai selectively prevented clotting in the coronary vasculature. PMID- 8471768 TI - A phase 1 study of adoptive transfer of autologous CD8+ T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS. AB - Based on preclinical studies showing that CD8+ T lymphocytes of human immunodeficiency syndrome (HIV)-infected subjects have anti-HIV activities, a phase 1 study was undertaken to determine the safety and feasibility of infusing in vitro purified, activated, and expanded CD8+ cells as a therapeutic measure in seven patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Autologous CD8+ cells were first selectively isolated in monoclonal antibody-coated flasks from peripheral blood mononuclear cells recovered by leukapheresis. They were then cultured and expanded with phytohemagglutinin and recombinant interleukin-2 (rIL-2) before infusion. Five cycles of isolations and infusions of increasing numbers of CD8+ T cells were achieved in five of seven subjects. Five cycles could not be completed in two subjects with AIDS whose CD4+ cell counts were < or = 48/microliters. Infusions of CD8+ cells alone were well tolerated. Four patients received rIL-2 by continuous infusion for 5 days with their final cycle of CD8+ cells. All developed reversible adverse effects attributable to rIL-2. After infusion, 111In labeled CD8+ cells quickly accumulated in the lungs, with less than 10% of the labeled cells remaining in the circulation. After 24 hours, labeled CD8+ cells were reduced in the lungs, but increased and persisted in liver, spleen, and bone marrow. Four of five patients who were treated with multiple infusions of CD8+ cells have improved or remained clinically stable, and the fifth developed Pneumocystis carinii pneumonia but recovered. This study demonstrated that infusion of autologous, in vitro expanded and activated CD8+ cells was feasible and clinically well tolerated in five of seven subjects with advanced HIV infections. PMID- 8471769 TI - Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study. AB - Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study. PMID- 8471770 TI - High frequency of monoallelic retinoblastoma gene deletion in B-cell chronic lymphoid leukemia shown by interphase cytogenetics. AB - Inactivation of the retinoblastoma tumor-suppressor gene (RB-1) has been associated with tumorigenicity in various human malignancies. In chronic lymphoid leukemias of B-cell origin (B-CLL) an involvement of RB-1 has been suggested based on cytogenetic data. We examined RB-1 and its chromosomal locus 13q14 in 35 cases of B-CLL by dual-color in situ hybridization to interphase nuclei and by G banding analysis of metaphase chromosomes. In one patient (pt) a monosomy 13, and in three other pts deletions involving or encompassing band 13q14 were detected by conventional cytogenetic analysis. In contrast, in situ hybridization to interphase nuclei showed a monoallelic RB-1 deletion in 11 cases (31%). One pt showed a translocation with the breakpoint in 13q1?4 on G-banding, but on in situ hybridization analysis the RB-1 signals were not affected. Our data show that RB 1 deletions can be diagnosed accurately by in situ hybridization on the one-cell level. The frequency of RB-1 deletions detected in this study is significantly higher than previously assumed in B-CLL, and seems to be in the same range as in retinoblastoma. PMID- 8471771 TI - Thrombospondin from activated platelets promotes sickle erythrocyte adherence to human microvascular endothelium under physiologic flow: a potential role for platelet activation in sickle cell vaso-occlusion. AB - Adherence of erythrocytes to vascular endothelium likely contributes to the pathophysiology of episodic vascular occlusion in patients with sickle cell disease (SCD). In addition, coagulation activation has been reported in sickle patients during complications such as pain episodes. To test the hypothesis that platelet activation contributes to sickle erythrocyte binding, we investigated whether factors released from activated sickle platelets promote adherence of sickle erythrocytes to human microvascular endothelial cells (MEC) under flow conditions. Activated sickle platelet supernatant (ASPS) promoted high levels of sickle erythrocyte adherence to MEC (55.4 +/- 3.9 erythrocytes/mm2) but only moderate adherence of normal erythrocytes to MEC (14.1 +/- 0.7 erythrocytes/mm2). When MEC were incubated with an antibody (OKM5) against CD36 (a thrombospondin [TSP] receptor), platelet supernatant mediated sickle erythrocyte adherence was inhibited 86%, suggesting that TSP participated in the adherence. To further define the role of TSP in adherence, additional studies using purified TSP were performed. At a concentration of 0.2 micrograms/mL TSP in serum-free media (SFM), sickle erythrocyte adherence to MEC was 33.9 +/- 2.7 erythrocytes/mm2 and sixfold greater than either sickle erythrocyte adherence in the absence of TSP or normal erythrocyte adherence in the presence of TSP. Doubling the concentration of TSP to 0.4 micrograms/mL proportionally increased adherence of sickle erythrocytes. Incubation of MEC with OKM5 or anti-alpha v monoclonal antibodies inhibited TSP mediated sickle erythrocyte adherence more than 95%. These data suggest that activated platelet release factors, including alpha-granule TSP, which promote receptor-mediated sickle erythrocyte adherence to microvascular endothelium. Such factors released during in vivo platelet activation could contribute to vaso occlusive complications by promoting erythrocyte adherence and microvascular occlusion. PMID- 8471772 TI - Distinct fetal Ank-1 and Ank-2 related proteins and mRNAs in normal and nb/nb mice. AB - Mice homozygous for the mutation normoblastosis (gene symbol nb on chromosome 8) are deficient in erythroid ankyrin (ANK-1) and have a severe hemolytic anemia throughout life. Characteristic of the disease is a dramatic decrease in the level of expression of the Ank-1 gene (chromosome 8). The other major ankyrin transcript, brain ankyrin (Ank-2 on chromosome 3) is expressed at normal levels in nb/nb mice. Surprisingly, nb/nb fetuses have normal erythrocyte counts despite the decreased levels of Ank-1 transcripts. We previously hypothesized that fetal specific ankyrin-related proteins could exist in nb/nb fetuses to account for the lack of detrimental effects of ANK-1 deficiency. In the present report, Western and Northern blot analyses were performed on hematopoietic cells isolated from nb/nb and +/+ fetuses. An ANK-1-related protein (165 Kd) in fetal reticulocytes persisted in adult nb/nb but not in +/+ reticulocytes. An Ank-1-related transcript of 5.5 kb was found in fetal reticulocytes. This transcript appeared to be upregulated in nb/nb but not in +/+ adult reticulocytes. A fetal-specific ANK-2-related protein (155 Kd) was present in nb/nb and in +/+ fetal reticulocytes. Ank-2-related fetal liver mRNAs were present during the time the liver was actively generating erythrocytes. Neither the Ank-2-related transcripts nor the 155-Kd ANK-2-related protein were found in +/+ or mutant adult reticulocytes. The data indicate that (1) unique ankyrin-related proteins and mRNAs present in fetal erythrocytes may stabilize the ankyrin-deficient nb/nb erythrocytes and (2) adult nb/nb mice may upregulate fetal gene transcripts to compensate for the ANK-1 deficiency. PMID- 8471773 TI - Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene. AB - The underlying DNA changes associated with glucose-6-phosphate dehydrogenase (G6PD)-deficient Asians have not been extensively investigated. To fill this gap, we sequenced the G6PD gene of 43 G6PD-deficient Chinese whose G6PD was well characterized biochemically. DNA samples were obtained from peripheral blood of these individuals for sequencing using a direct polymerase chain reaction (PCR) sequencing procedure. From these 43 samples, we have identified five different types of nucleotide substitutions in the G6PD gene: at cDNA 1388 from G to A (Arg to His); at cDNA 1376 from G to T (Arg to Leu); at cDNA 1024 from C to T (Leu to Phe); at cDNA 392 from G to T (Gly to Val); at cDNA 95 from A to G (His to Arg). These five nucleotide substitutions account for over 83% of our 43 G6PD-deficient samples and these substitutions have not been reported in non-Asians. The substitutions found at cDNA 392 and cDNA 1024 are new findings. The substitutions at cDNA 1376 and 1388 account for over 50% of the 43 samples examined indicating a high prevalence of these two alleles among G6PD-deficient Chinese. Our findings add support to the notion that diverse point mutations may account largely for much of the phenotypic heterogeneity of G6PD deficiency. PMID- 8471774 TI - Human erythrocyte protein 4.2 deficiency associated with hemolytic anemia and a homozygous 40glutamic acid-->lysine substitution in the cytoplasmic domain of band 3 (band 3Montefiore). AB - Red blood cell (RBC) protein 4.2 deficiency is often associated with a moderate nonimmune hemolytic anemia, splenomegaly, and osmotically fragile RBCs resembling, but not identical to, hereditary spherocytosis (HS). In the Japanese type of protein 4.2 deficiency (protein 4.2Nippon), the anemia is associated with a point mutation in the protein 4.2 cDNA. In this report, we describe a patient with moderate and apparently episodic nonimmune hemolytic anemia with splenomegaly, spherocytosis, osmotically fragile RBCs, reduced whole cell deformability, and abnormally dense cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the proposita's RBC membrane proteins showed an 88% deficiency of protein 4.2 and a 30% deficiency of glyceraldehyde-3-phosphate dehydrogenase (band 6). Structural and molecular analyses of the proposita's protein 4.2 were normal. In contrast, limited tryptic digestion of the proposita's band 3 showed a homozygous abnormality in the cytoplasmic domain. Analysis of the pedigree disclosed six members who were heterozygotes for the band 3 structural abnormality and one member who was a normal homozygote. Direct sequence analysis of the abnormal band 3 tryptic peptide suggested that the structural abnormality resided at or near residue 40. Sequence analysis of the proposita's band 3 cDNA showed a 232G-->A mutation resulting in a 40glutamic acid ->lysine substitution (band 3Montefiore). Allele-specific oligonucleotide hybridization was used to probe for the mutation in the pedigree, showing that the proposita was homozygous, and the pedigree members who were heterozygous for the band 3 structural abnormality were also heterozygous for the band 3Montefiore mutation. The band 3Montefiore mutation was absent in 26 chromosomes from race matched controls and in one pedigree member who did not express the band 3 structural abnormality. In coincidence with splenectomy, the proposita's anemia was largely corrected along with the disappearance of most spherocytes and considerable improvements of RBC osmotic fragility, whole cell deformability, and cell density. We conclude that this hereditary hemolytic anemia is associated with the homozygous state for band 3Montefiore (40glutamic acid-->lysine) and a decreased RBC membrane content of protein 4.2. We speculate that band 3 structural abnormalities can result in defective interactions with protein 4.2 and band 6, and in particular, that the region of band 3 containing 40glutamic acid is involved directly or indirectly in interactions with these proteins. PMID- 8471775 TI - A comparative study of the iron-clearing properties of desferrithiocin analogues with desferrioxamine B in a Cebus monkey model. AB - A comparative study of the iron-clearing properties of subcutaneously administered desferrioxamine B (DFO) with those of orally administered desferrithiocin sodium salt (1), desmethyl desferrithiocin (2), desazadesmethyl desferrithiocin sodium salt (3), desazadesmethyl desferrithiocin pivaloyloxymethyl ester (4), and desazadesmethyl-5,5-dimethyl desferrithiocin (5) in an iron-loaded Cebus monkey model and a non-iron overloaded bile duct cannulated rat model is presented. All six drugs, which performed well in rodent studies, demonstrated increased efficiency in the Cebus monkey model. When administered to rodents at a daily dosage of 384 mumol/kg over a period of 10 days, drug 1 demonstrated severe renal toxicity. whereas drugs 3, 4, and 5 exhibited severe gastrointestinal (GI) toxicity. Under the same experimental protocol, drug 2 did not show significant toxic side effects. In addition, to further evaluate the iron-clearing properties of analogue 2, a dose-response study was performed in the primates that showed that iron excretion increased in a dose-dependent fashion. PMID- 8471776 TI - Antenatal management of severe feto-maternal alloimmune thrombocytopenia: HLA incompatibility may affect responses to fetal platelet transfusions. AB - In feto-maternal alloimmune thrombocytopenia (FMAIT), severe hemorrhage, particularly intracranial haemorrhage (ICH), may occur before delivery. Management strategies to prevent ICH in high-risk pregnancies include maternal administration of intravenous Ig with or without steroids and fetal platelet transfusions. This report describes a patient who lost three fetuses with ICH because of FMAIT due to anti-HPA-1a. ICH occurred earlier in successive pregnancies (at 28, 19, and 16 weeks of gestation) despite maternal treatment with intravenous Ig and steroids from 14 weeks of gestation in the third pregnancy. The fourth pregnancy was managed by administering weekly intraperitoneal injections of Ig to the fetus from 12 to 18 weeks of gestation. At 18 weeks, there was no evidence of ICH, but the fetal platelet count was only 12 x 10(9)/L. Serial fetal platelet transfusions were started, but there were poor responses because of immune destruction of the transfused platelets by maternal HLA antibodies. There were improved responses to transfusions prepared from the mother and from HLA-compatible HPA-1a-negative donors. At 35 weeks of gestation, a normal infant was delivered by Caesarean section after 20 platelet transfusions. There was prolonged thrombocytopenia in the baby for 15 weeks after birth, probably due to transfer of HPA-1a antibodies in the transfusions of unwashed maternal platelets. The optimal management of pregnancies likely to be severely affected by FMAIT is still evolving. Intensive management was successful in this case, but a successful outcome cannot be guaranteed in severely affected cases. This is the first time that HLA incompatibility has been found to complicate fetal transfusion therapy. PMID- 8471777 TI - A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group. AB - The development of antibodies to factor VIII (inhibitors) in response to clotting factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8471778 TI - A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study. AB - Two novel preparatory regimens for conditioning of patients with leukemia for allogeneic bone marrow transplantation (BMT) from histocompatible sibling donors have been tested in a phase III trial under the auspices of the Southwest Oncology Group (SWOG 8612). These two regimens consisted either of fractionated total body irradiation and etoposide (FTBI/VP-16) or high-dose busulfan with cyclophosphamide (BU/CY). Only patients who had failed prior conventional management at least once were study eligible, ie, no patients with acute leukemia in first remission (CR) or in first chronic phase (CP) of chronic myelogenous leukemia (CML) participated. Patients were stratified according to the following risk criteria: "good-risk" patients were those who were in second CR of their acute leukemia or in accelerated phase (AP) of CML; "poor-risk" patients had further advanced stages of leukemia. During a 52-month period, 131 patients were registered of whom 122 (93%) were study eligible. Sixty-one eligible patients were randomized to the FTBI/VP-16 arm and 61 to the BU/CY regimen. Of these 122 patients, 114 (93%) proceeded to BMT according to protocol. Posttransplant immunosuppression to prevent graft-versus-host disease (GVHD) consisted of cyclosporine and prednisone (CSA/PSE). Neither overall survival nor disease-free survival (DFS) differed significantly between the two treatment groups (P = .89 and .69, respectively). Estimated DFS for "good-risk" patients who had been prepared with the FTBI/VP-16 regimen was 55% +/- 11%, as compared with patients treated with BU/CY whose DFS figure was 34% +/- 10% (P = .30). For "poor-risk" candidates, the DFS rates at 24 months were 17% +/- 6% (for FTBI/VP-16) and 24% +/- 8% (for BU/CY), respectively (P = .81). These figures do not differ significantly, especially in view of the fact that the "good-risk" patients prepared with the FTBI/VP-16 regimen were younger than those treated with BU/CY. Both regimens were well tolerated with no regimen-related deaths encountered during the 6-week period after BMT. This study also confirmed the efficacy of the CSA/PSE combination in the prevention of GVHD with 23 of 113 (20%) of BMT recipients developing moderate to severe acute GVHD. The leading cause for treatment failure was leukemic relapse (45 of the 114 BMT recipients suffered a recurrence of their leukemia), whereas 38 patients died without evidence of relapse. Thirty-one patients are alive and in continued CR after marrow transplantation; four are alive in relapse.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8471779 TI - Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes. AB - Preparative regimens containing busulfan (BU) followed by allogeneic bone marrow transplantation (BMT) were used in 27 consecutive patients with myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary MDS, 11 other patients had antecedent hematologic diseases or developed MDS after cytotoxic and/or radiation therapy. Six patients had leukemic transformation and received antileukemic therapy before BMT. Pre-BMT cytogenetic studies showed complex chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days, cytosine arabinoside (ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from hepatic veno-occlusive disease, 3 from sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute graft-versus-host disease, 1 from hemolytic uremic syndrome with adult respiratory distress syndrome, 1 from bronchiolitis obliterans, and the only patient who did not engraft died from acute myeloid leukemia. Regimen related toxicities (RRT) include GI tract (diarrhea, 14; stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen. PMID- 8471780 TI - Correlation of minor histocompatibility antigen-specific cytotoxic T lymphocytes with graft-versus-host disease status and analyses of tissue distribution of their target antigens. AB - Peripheral blood mononuclear cells (PBMC) from 17 patients receiving HLA identical sibling bone marrow grafts were stimulated with host pretransplant PBMC. Cytotoxic T-cell lines (TCL) with specificity for host pretransplant PBMC were obtained from 9 of these patients, all presenting with severe graft-versus host disease (GVHD), but from none of the remaining cases lacking evidence of disease. Cytotoxic TCL were specific for host targets and failed to lyse donor cells. Monoclonal antibodies (MoAbs) blocking experiments and donor population screening analyses demonstrated that minor histocompatibility antigen (MiHA) specific lysis of host targets was restricted by class I major histocompatibility complex (MHC) determinants. Whereas hematopoietic cells such as phytohemagglutinin (PHA) blasts or lymphoblastoid cell lines were susceptible to lysis by MiHA-specific TCL, keratinocytes (K) representing the natural targets of GVHD were quite resistant. Quantitative radioimmunometric measurements indicated very low constitutive expression of class I MHC antigens on K targets, which was readily increased by treatment with interferon-gamma (IFN-gamma). IFN-gamma treatment at the same time rendered these cells susceptible to lysis by MiHA specific TCL. Host leukemic cells of 3 patients were recognized by MiHA-specific TCL in a chromium release assay and in one experiment host leukemic cells were effectively killed and their growth specifically inhibited in a leukemia colony assay by a clone. These data demonstrate that (1) host-specific cytotoxic TCL are detected exclusively in the PB of patients with acute GVHD grades II through IV after allogeneic matched bone marrow transplantation, and (2) their target antigens are simultaneously expressed on several host cell lines, including lymphoblastoid cell lines, PHA blasts, leukemic cells, and K. We also extend previous findings by showing that, besides the expression of the nominal MiHA, the density of the restricting class I MHC elements also crucially determines the extent of TCL lysis. Because of its capacity to enhance class I MHC antigen expression, IFN-gamma represents a key cytokine for determining the susceptibility of MiHA targets for lysis by TCL and clones, and in one patient an MiHA-specific clone recognized host leukemic cells and also inhibited host leukemic cell growth in a colony inhibition assay. PMID- 8471781 TI - Diagnosis and incidence of acute promyelocytic leukemia (FAB M3 and M3 variant) in childhood. PMID- 8471782 TI - Electroneurography: electrical evaluation of the facial nerve. AB - This article provides an introduction, anatomic considerations, and description of technique for the performance of electroneurography. Two case studies are provided as illustrations. PMID- 8471783 TI - Audiologic and otolaryngologic findings in progeria: case report. AB - Progeria is a rare syndrome, with an estimated incidence of 1 per 250,000 births. Although children with progeria have the appearance of premature aging or senility, the term is misleading because reported cases of progeria have not manifested most physical or biochemical aspects of old age. Many children with progeria appear normal at birth and then progressively, and rather rapidly, develop the characteristic features during early childhood. Although first described in the 1880s, only approximately 100 cases of progeria are reported in the international literature. The single case study of hearing in progeria, which appeared in 1965, is limited to pure-tone and speech audiometry findings. We report the results of otolaryngologic examination and pure-tone, speech, immittance, and auditory brainstem response (ABR) audiometry for a 5-year-old female with progeria. The patient had a mild-to-moderate, bilateral, conductive hearing loss. Immittance measurements were consistent with fixation of the ossicular chain and this was confirmed surgically. Mildly prolonged ABR wave I-V latencies suggest possible auditory central nervous system involvement. PMID- 8471784 TI - Case studies in binaural interference: converging evidence from behavioral and electrophysiologic measures. AB - We present four case reports of elderly hearing-impaired persons demonstrating a binaural interference effect. Performance measures were poorer when stimulation was binaural than when it was monaural. In the first case the effect is shown for aided speech recognition scores. In the second case it is shown in topographic brain maps of the middle-latency auditory evoked potential. In the third and fourth cases it is shown for both aided speech recognition and the middle-latency response. The effect may be analogous to the phenomenon of binocular rivalry in the visual domain. PMID- 8471785 TI - Audiometry in the sound field. PMID- 8471786 TI - Status of sound field audiometry among audiologists in the United States. AB - Results of a national survey on sound field usage and sound field calibration are presented. Respondents to the survey were 418 ASHA certified audiologists, who answered questions on demographic variables, sound field testing conditions, and sound field calibration procedures. Demographic characteristics of the respondents indicate that they were representative of ASHA certified audiologists. Eighty-one percent of the respondents use sound field audiometry as part of their audiologic practice. Electroacoustic calibration of the sound field stimuli is done most often by an equipment technician, and only a small percentage of the respondents knew how the calibration was done. Results show a lack of standardization among sound field test rooms, great diversity in the stimuli used for sound field testing, and inconsistent calibration methods. Results indicate the need for standards and improved preservice and in-service training in sound field calibration techniques. PMID- 8471787 TI - Reexamination of gender differences in the source location of N1m. AB - Gender differences in the source location of the auditory evoked field (AEF) component N1m have been reported previously in a small group of subjects. The present study was conducted to evaluate further the existence of gender differences in a larger sample. Neuromagnetic recordings of AEFs were obtained from young normal hearing subjects using a 1000-Hz tone burst presented at 60 dB hearing level (HL). No significant gender-related differences were observed for the N1m peak latencies following left and right ear stimulation. The stimulating parameters and larger sample used in the present study size may account for the difference in gender effects observed between the two studies. PMID- 8471788 TI - Interaural attenuation using insert earphones: electrocochleographic approach. AB - We measured the interaural attenuation for click stimuli using insert earphones. Electrocochleographic thresholds were determined when clicks were presented both ipsilaterally and contralaterally to the recording ear. The interaural attenuation was calculated as the difference between ipsilateral and contralateral thresholds. Results from normal listeners showed that crossover occurred. Results agree with previous investigators who used a different approach. Results confirm that one may need to mask the nontest ear in clinical evoked potential testing even though insert earphones are used. Several approaches to the question of when to mask are proposed. PMID- 8471789 TI - Computer simulation technique for assessing pediatric auditory test protocols. AB - Adaptive testing procedures are widely used for evaluating the hearing of young children. A standard protocol for such testing, however, has not been recommended and, as a result, many variations of the procedure are used clinically. This study, by utilizing computer simulations, varied several test parameters and examined the resulting test outcomes. We evaluated the effects of starting level, stimulus step size, and the use of conditioning trials on test outcome, while also varying the hearing levels and false positive and and negative rates of our simulated subjects. Results indicated that a low starting level, with a 20-dB down 10-dB up step size, and no conditioning trials produced the most accurate estimates of thresholds under most conditions. PMID- 8471790 TI - Evaluating performance with high-frequency emphasis amplification. AB - Hearing aid fitting for individuals with high-frequency impairment has been difficult because of the limited gain available at those frequencies. Special high-frequency emphasis hearing aids have been developed in an attempt to alleviate this problem. The insertion-gain responses and changes in speech recognition performance (in quiet and in noise, aided and unaided) were measured for a commercially available high-frequency emphasis hearing aid, using two types of speech materials (nonsense syllables, monosyllabic words). The maximum obtainable gain observed for high frequencies approximated that prescribed by the NAL-R method, but was considerably lower than that prescribed by other common prescriptive methods. Furthermore, modest improvements in speech recognition were found. When evaluating individuals with high-frequency impairment, speech materials administered in noise appeared to be the most sensitive indication of improved speech recognition. Special high-frequency emphasis speech materials (CUNY NST) were no more sensitive to improvements in performance than conventional clinical word lists (NU6). PMID- 8471791 TI - Tactile-auditory speech perception by unimodally and bimodally trained normal hearing subjects. AB - The following study compared the effectiveness of unimodal and bimodal training strategies at improving the perception of speech information under a variety of conditions. Normal-hearing subjects were trained in the perception of vowel and consonant stimuli. Speech information was provided either via a multiple channel electrotactile speech processing aid (the Tickle Talker), and/or by a 200-Hz low pass filtered auditory signal. Two subjects were trained only in the combined tactile-plus-auditory (TA) condition; the remaining two were trained in both the tactile-alone (T) and auditory-alone (A) conditions; however, only one condition was used at any single time. All subjects were evaluated in the TA, T, and A conditions, both at the beginning of the study, prior to training, and at the completion of training, on closed-set vowel and consonant confusion tests, and on an open-set word test. Results indicated that whilst statistically significant improvements occurred from one evaluation period to the next, in both groups of subjects, the improvements per condition were not dependent on the type of training received. The results provide a preliminary indication that the provision of unimodal training does not impair the perception of speech information under bimodal perception conditions. PMID- 8471792 TI - Increased expression of the calmodulin gene of the late blight fungus Phytophthora infestans during pathogenesis on potato. AB - In order to isolate in planta-induced genes encoding putative pathogenicity factors of the late blight fungus Phytophthora infestans, a genomic library was differentially screened. For the differential hybridization, labeled first-strand cDNA synthesized on mRNA isolated from P. infestans-infected potato leaves and on mRNA isolated from the fungus grown in vitro were used as probes. This screening resulted in the isolation of the P. infestans calmodulin gene. The gene, designated calA, contains an open reading frame of 447 base pairs without introns and is unique in the P. infestans genome. The predicted amino acid sequence is 89.9-94.6% identical to calmodulins from higher eukaryotes, whereas the identity to calmodulins of higher fungi is significantly less (60.8-85.1%). Expression studies revealed that the P. infestans calA gene is constitutively expressed in in vitro grown mycelium. However, during pathogenesis on potato the level of P. infestans calmodulin mRNA is increased approximately fivefold. PMID- 8471793 TI - Severe chlorotic spot symptoms in cucumber mosaic virus strain Y-infected tobaccos are induced by a combination of the virus coat protein gene and two host recessive genes. AB - To investigate the genetic determinants of severe chlorotic spot symptoms in cucumber mosaic virus (CMV[Y])-inoculated tobacco (Nicotiana tabacum 'Ky57') leaves, symptom expression was compared among tobaccos (N. tabacum 'Ky57', N. tabacum 'Xanthi nc', and their hybrids) inoculated with CMV(Y), CMV(O), or pseudorecombinants of both strains of CMV. Xanthi nc showed very mild chlorotic spot symptoms in CMV(Y)-inoculated leaves. Both CMV(O)-inoculated Ky57 and Xanthi nc leaves showed no symptoms. In pseudorecombinant-inoculated Ky57 leaves, severe symptoms were determined by chimeric CMV(O) and CMV(Y) RNA3 transcripts, which contained most of the coat protein gene of CMV(Y). Genetic analysis of severe symptom formation in CMV(Y) or pseudorecombinant-inoculated tobaccos indicated that two recessive nuclear-coded host genes determined severe symptom formation in CMV(Y)-inoculated Ky57. The two recessive host genetic loci completely cosegregated with the two recessive burley loci (yb1 and yb2 genes) of Ky57, whose character is an apparent reduction in chlorophyll of the stems. When several cultivars of N. tabacum were inoculated with CMV(Y), all burley tobaccos clearly showed severe symptoms, but most other cultivars showed very mild symptoms. These results suggest that severe chlorotic spot symptom formation in CMV(Y)-inoculated Ky57 is induced by a combination of the virus coat protein gene and two recessive host genes that are closely linked to or identical to yb genes. PMID- 8471794 TI - Characterization of two putative pathogenicity genes of the fungal tomato pathogen Cladosporium fulvum. AB - The fungus Cladosporium fulvum is a biotrophic pathogen of tomato. On susceptible tomato plants, the fungus grows abundantly in the extracellular spaces between the mesophyll cells. The mechanism by which C. fulvum is able to establish and maintain basic compatibility on its one and only host species, the tomato, is unknown. The isolation and characterization of pathogenicity factors and the corresponding genes will provide insight into the mechanism by which C. fulvum colonizes its host. Two putative pathogenicity genes of C. fulvum encoding proteins, which occur abundantly in the extracellular space of infected tomato leaves, were isolated and characterized (ecp1 and ecp2). The DNA sequences of these ecp genes (encoding extracellular protein) do not share homology to any sequence present in the DNA databases. The ecp genes are highly expressed in planta but not in vitro, suggesting that they play a significant role in pathogenesis. PMID- 8471795 TI - Interaction of Xanthomonas campestris with Arabidopsis thaliana: characterization of a gene from X. c. pv. raphani that confers avirulence to most A. thaliana accessions. AB - Infiltration of leaves of Arabidopsis thaliana accession Columbia with Xanthomonas campestris pathovar campestris leads to bacterial growth and disease symptoms reminiscent of those incited in Brassica plants inoculated under the same conditions. A search among A. thaliana accessions for variation in the reaction phenotype to strains of X. campestris pathovars campestris, aberrans, and raphani showed that there were no clear differential responses between plant accessions to the individual bacterial strains tested. X. c. pv. raphani strain 1067 was avirulent to all A. thaliana accessions tested. A gene was cloned from X. c. pv. raphani 1067 which, when transferred into the virulent X. c. pv. campestris strain 8004, strongly reduced symptom development and bacterial growth in A. thaliana Columbia plants but did not affect virulence to Brassica plants. The gene (denoted avrXca) interacted with all A. thaliana accessions tested except one, Kas-1, which developed disease symptoms and supported growth of the transconjugant to levels similar to those with X. c. pv. campestris 8004 alone. Sequence analysis of avrXca revealed a probable open reading frame encoding a protein of 66,566 Da that has no homology with other known sequences. A sequence motif conserved among hrp genes was identified in the 5' noncoding region of avrXca, and features characteristic of a signal peptide were found in the N terminal portion of the presumed AvrXca protein. DNA from different phytopathogenic bacteria contained sequences hybridizing with avrXca in related X. campestris pathovars but not in Erwinia or Pseudomonas strains. PMID- 8471796 TI - Azorhizobium caulinodans nitrogen fixation (nif/fix) gene regulation: mutagenesis of the nifA -24/-12 promoter element, characterization of a ntrA(rpoN) gene, and derivation of a model. AB - Using site-directed mutagenesis, mutations were introduced in the -24/-12 promoter element of the Azorhizobium caulinodans nifA gene, and chimeric nifA lacZ reporter gene fusions were constructed. Single base-pair mutations in the conserved -25 or -13 G residues were found to reduce or abolish nifA promoter activity, respectively, demonstrating that the -24/-12 promoter element is important for nifA gene expression and suggesting the involvement of a sigma 54 (NtrA/RpoN)-type transcription factor in nifA gene regulation. A 2-bp mutation at positions -25 and -16 was found to create a relatively nitrogen-control independent, highly expressed nifA promoter. Using a heterologous ntrA(rpoN) gene probe, an A. caulinodans ntrA(rpoN)-like gene was cloned and the DNA sequence of this gene and flanking regions was determined. The presence of three open reading frames (ORF1-3) was demonstrated. ORF2 was found to contain regions sharing a high degree of homology with all characterized bacterial ntrA(rpoN) genes. ORF1 was found to share homology with ORFs found upstream of other bacterial ntrA(rpoN) genes, which have been postulated to encode members of a superfamily of ATP-binding proteins. Transposon Tn5 insertion mutations were introduced into the cloned ntrA(rpoN) gene, and chromosomal ntrA(rpoN)::Tn5 A. caulinodans mutants were created. The resulting mutants were found to be unable to fix nitrogen in the free-living state (Nif- in culture) or in stem or root nodules induced on Sesbania rostrata (Fix- in planta), and to be unable to grow aerobically in the presence of nitrate as sole nitrogen source (Ntr-). A nifH lacZ gene fusion was found to be silent in ntrA(rpoN)::Tn5 mutant strains, but a nifA-lacZ gene fusion was found to be expressed at a wild-type level, suggesting that the ntrA(rpoN) gene identified here controls the expression of some of the A. caulinodans nif genes, but not the central nif regulatory gene nifA. Based on these results, a new model for the regulation of nif/fix gene expression in A. caulinodans is proposed. PMID- 8471797 TI - Repeated injections of interferon-alpha A/D in Balb/c mice: behavioral effects. AB - Interferon-alpha decreases food intake and activity in mice and humans. The present study further explores parallels between effects of this protein in humans and mice, using a hybrid recombinant interferon-alpha A/D (INF-alpha A/D) that has antiviral and hepatic activity in mice. Measures of activity (open field), muscle strength (forelimb grip strength), and motor ability (swim posture and endurance with 0, 3, and 6% added weight) were examined in Balb/c mice injected with 1600 U/g of hybrid rhuIFN-alpha A/D daily for 5 days (n = 9) or with IFN vehicle (n = 11). Open field activity was significantly depressed in the group exposed to IFN. The number of times the nose dipped under the water when swimming with 3% added body weight was higher in the IFN-treated mice, while float time was decreased with 6% added weight. The IFN-treated mice were slower to adopt the new strategies necessary to swim with added weight. Depression of motor activity is a robust, general effect of IFN treatment observed in this as well as previously published studies. Together, these studies demonstrate activity decrements in two different strains of mice, two different activity measures, acute and chronic injections, and recombinant and nonrecombinant IFN preparations. PMID- 8471798 TI - Exposure to conspecific alarm chemosignals alters immune responses in BALB/c mice. AB - Male BALB/cJ mice were exposed for 24 h to odors from donor mice that were either footshocked or undisturbed. Mice exposed to odors from footshocked donors had suppressed splenic IL-2 production following in vitro concanavalin A (Con A) stimulation compared to home cage or apparatus controls. Stress odor exposure also resulted in reduced natural killer (NK) cell cytotoxicity against YAC-1 tumor target cells compared to controls. Stress odor exposure 24 h after intraperitoneal injection of keyhole limpet hemocyanin (KLH) increased IgM and IgG antibody titers relative to the response of home cage or apparatus control animals. These results demonstrate that exposure to olfactory cues from stressed rodents alters both cellular and humoral immune responses. This paradigm may provide an ethnologically appropriate model of psychosocial stress in rodents. PMID- 8471799 TI - Effect of neuropeptide Y on natural killer activity of normal human lymphocytes. AB - The in vitro effect of neuropeptide Y (NPY) on natural killer (NK) cell activities of normal lymphocytes was investigated. NPY at 10(-9) to 10(-12) M concentrations produced significant suppression of NK activity against K 562 target cells. NPY at 10(-9) to 10(-12) M concentrations also produced significant inhibitory effects on NK activities of NK-enriched large granular lymphocytes against LAV-infected 8E5/LAV target cells. The suppression was dose dependent against both targets. NPY-induced suppression of NK activity of lymphocytes against K 562 target cells was specifically reversed by rabbit anti-NPY antisera at 1:800 and 1:1600 dilutions, showing the specificity of reactions. Pretreatment of target cells with NPY concentrations capable of inhibiting NK activity did not affect the sensitivity of K 562 target cells for lysis by effector cells. Inhibition of cytotoxicity was not due to direct toxicity of effector cells, because lymphocytes treated with NPY showed normal levels of 51Cr release and their viability was comparable to that of untreated control cells. These studies demonstrated that NPY, a product of sympathetic nervous system activation, may have a significant immunoregulatory effect on NK cell activities of normal lymphocytes that may be of clinical significance. PMID- 8471800 TI - Trait anxiety and anticipatory immune reactions in women receiving adjuvant chemotherapy for breast cancer. AB - We compared peripheral blood cell counts as well as mitogen activity and natural killer-cell activity in women undergoing adjuvant chemotherapy for breast cancer in the hospital prior to chemotherapy with assessment at home 2 days earlier. Patients compared to controls had an increased number of white blood cell counts in the hospital as compared to those at home, mediated by an increased total number of granulocytes. Among patients, those with high compared to low trait anxiety evidenced immune system changes. Total number of monocytes were reduced in patients with high compared to low trait anxiety and natural killer-cell activity tended to be compromised in the high anxiety group. Helper/inducer T cells isolated from hospital blood samples were lower in patients with high as compared to low trait anxiety, while no difference was observed in samples taken at home. Conditioned nausea was associated with trait anxiety and patients with as compared to without conditioned nausea displayed immune changes similar to changes observed as a function of trait anxiety. State anxiety measured at the hospital did not relate to immune measures. The observed increase in granulocytes is consistent with an interpretation both in terms of conditioning and anticipatory stress. The anticipatory immunosuppression in patients with high compared to low trait anxiety is consistent with the hypothesis that chemotherapy patients may develop conditioned immunosuppression after repeated pairings of treatment-related stimuli with the unconditioned immunosuppressive effect of chemotherapy. PMID- 8471801 TI - Immune responses in male mice with aggressive and submissive behavior patterns: strain differences. AB - Immune responses in two strains of male mice with aggressive and submissive behavior patterns was studied. In aggressive CBA males immunized on the 10th day of agonistic confrontations with submissive partners, greater numbers of plaque forming cells (PFC) and rosette-forming cells (RFC) were noted compared to control mice. Unlike the CBA strain, both PFC and RFC levels in aggressive C57BL males did not increase, but both PFC and RFC numbers decreased in submissive animals. PMID- 8471802 TI - [Laudatio]. PMID- 8471803 TI - [Social medicine: why--how--what for? (Social medicine and anthropology)]. AB - The speech held on the occasion of the Salomon Neumann Medal Award 1992 describes with biographical pointers how an internistic clinician (for outpatients) developed towards taking up social medicine as his specialty. The starting point was the management and care of patients suffering from chronic diseases. This was an important step in the direction towards "successful conditional healthiness". The conditions included in the concept are both of a personal and of a sociological nature, i.e. shared by many. They are dealt with by social medicine and also by medical sociology, the separation of which constituted an painful disappointment. Arguments against a dichotomy of social medicine and medical sociology are also supplied by looking back on the history of ideas with emphasis on ancient dietetics and ecology, the early Age of Enlightenment (Leibniz) and the 19th century (Virchow, Neumann). It is suggested to create an active link between social medicine as the overriding concept and epidemiology, social hygiene and medical sociology as subsumptions. PMID- 8471804 TI - [Portrayal of the chronic patients in literature of the 19th century]. AB - Chronic disease appears in the literature and fine arts of the 19th century in its manifestations, its causes and its therapy, as well as its symbolism. Examples of persuasive characters are portrayed next to negative ones-in the respective roles of the patient, the physician, the nurse, as well as of the relatives. The limits of medicine are also made apparent as well as possibilities presented for ways of giving a human meaning to the suffering, disease and death. PMID- 8471805 TI - [Ethics in epidemiology]. AB - Progress in epidemiology was instrumental for recognising health risk factors and emphasising health protection and health risk prevention; it may contribute to a Copernican turn in setting new priorities in health care politics and health care ethics, in redefining health, disease, and individual health literacy and responsibility. This paper reviews recent national and international activities to formulate a Code of Ethics for Epidemiologists and evaluates central bioethical principals for epidemiologists. PMID- 8471806 TI - [Expert evaluation and rehabilitation of nonspecific pain conditions]. AB - Daily expertising practice shows that in case of exclusively somatically induced unspecific pain chronification is greatly enhanced. Faced with such phenomena, it is suggested that a dualistic manner of interpretation and treatment taking into consideration in equal measure both somatic and psychosocial factors and their mutual interaction, may initiate a change in the general trend of the patient's complaints towards eventual relief. PMID- 8471807 TI - [Food borne outbreak of a Salmonella enteritidis epidemic in a large pharmaceutical industry]. AB - In summer 1991 an outbreak of a Salmonella enteritidis epidemic involving about 600 cases of gastroenteritis occurred at one of the leading pharmaceutical companies in southwestern Germany. The main source was a cold fruit soup, in addition Salmonella were isolated from meat strips and a curd cheese which were used for a salad dressing. A total of 2300 contaminated food portions were served resulting in an attack rate of about 25%. The possible origin could have been an asymptomatic Salmonella-positive member of the kitchen personnel who was the only one who was involved with the preparation of all the incriminated foods. A further spread of the epidemic and especially the possible contamination of pharmaceuticals was avoided by the timely and adequate reaction of the company's occupational medical service. This case exemplifies how classical crisis management, "increased initiative on one's own for prevention of infections in all areas of food processing" (Steuer) and finally the cooperation of the company with different institutions of the public health authorities contribute to the control of such a catastrophic scenario. PMID- 8471808 TI - [Malaria travel disease--importation to Germany 1988]. AB - Malaria continues to be an important travellers' disease in Germany. In 1988 885 cases of malaria were imported into the Federal Republic of Germany. German tourists to far-away countries represented the biggest share (about 80%). Africa was the most prominently represented continent with 76%. Differentiation according to species of pathogens showed that 68% of the diseases were caused by Plasmodium falciparum. 11 patients died of malaria in 1988, in all cases due to P. falciparum infection. The mortality of the patients increases with age. Only in 5 of 11 persons who died there had been a sufficient prophylaxis against malaria, at least as far as the anamnesis revealed. Careful planning of sufficient prophylaxis taking into consideration the partly very marked resistance to a multitude of drugs, as well as competent medical advice to would be travellers, are imperative before the number of malaria imports into Germany can be reduced. PMID- 8471809 TI - [Health care structure legislation--reform of health insurance]. AB - On January 1st, 1993, the German Health Care Structure Reform Act has come into effect. It will fundamentally change the system of health insurance as well as the health care system. By the reform act, new structural and controlling elements have been installed in all central branches of health care, and, at the same time, a new order for the competition between the sickness funds has been established. Far-reaching structural alterations affect the hospital sector, the drug market and the system of ambulatory care. In the hospital sector, there will be a change-over to a price system consisting of special payments, payment according to diagnostic-related groups, and differentiated per-diem rates. On the drug market there will be introduced, besides a drug budget for doctors, a positive list for pharmaceuticals which will be worked out jointly by representatives of the medical profession and the sickness funds. In the ambulatory sector, licensing restrictions for doctors intending to set up practice will be introduced and the importance of the general practitioner or family doctor will be enhanced. The Health Care Structure Reform Act provides for self-government of the sickness funds and the medical profession with a wide range of controlling and shaping instruments. It also places the Ministry of Health in a better position to take influence. After the expire of the budgeting phase, competitive elements resp. extended controlling measures in the contracts sector will become more and more important features of the health care system. It remains to be seen whether the new controlling instruments will suffice to cause the intended limitation of expenditure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471810 TI - [Report of the 28th Annual Congress of the German Society of Social Medicine and Prevention--Lubeck, 29 September-3 October 1992]. PMID- 8471811 TI - Current therapy of systemic sclerosis (scleroderma). AB - Treatment of systemic sclerosis (scleroderma) presents a challenge to both the patient and the physician. Established approaches include long-term physiotherapy, disease-modifying agents such as D-penicillamine, and treatment of organ involvement. These efforts are often unsatisfactory since the results are poor. However, recent advances include treatment of Raynaud's phenomenon (plasmapheresis, stanozolol, and prostacyclin analogues), scleroderma renal crisis (angiotensin-converting enzyme inhibitors), and gastric hypomotility (cisapride). This article covers the current approaches to the disease-modifying therapy including those related to the function of collagen-producing fibroblasts, vascular alterations, and the cellular and humoral immune system, as well as treatment of involved organs. PMID- 8471812 TI - Lipoatrophic diabetes. PMID- 8471813 TI - The effect of the apolipoprotein E polymorphism on lipid levels in patients with familial defective apolipoprotein B-100. AB - Serum lipid concentrations of patients with familial defective apolipoprotein B 100 (FDB) show a high interindividual variability although the underlying defect is caused by a single point mutation. On the other hand, several genetic factors modulating serum cholesterol levels are known, such as DNA polymorphisms of the apolipoprotein B or the apolipoprotein E (apo E) gene. To assess the effect of the apo E polymorphism on serum cholesterol, lipid levels of FDB patients (n = 36) were compared with those of a normolipidemic control group (n = 272) according to their apo E genotype. For the FDB group mean values of low-density lipoprotein (LDL) cholesterol (mg/dl) were 225.7 +/- 53.7 for E3/2 genotype (n = 3), 234.2 +/- 48.3 for E3/3 genotype (n = 20), and 252.4 +/- 73.8 for E4/3 genotype (n = 13). Means of triglycerides (mg/dl) were 121.0 +/- 21.2, 114.8 +/- 60.7, and 110.0 +/- 62.8 for the respective apo E genotypes. The calculated average effect of the apo E alleles on LDL cholesterol levels was -6.0% for allele e2 and +3.7% for e4 relative to the whole FDB group. The effect on triglyceride levels was +7.5% for e2 and -3.6% for e4. The control group showed a similar variation in LDL cholesterol depending on the different apo E genotypes. About 6% of the total variation in LDL cholesterol can be accounted for by the apo E locus in normolipidemic and hypercholesterolemic individuals alike. PMID- 8471814 TI - Periodic respiration in patients with heart failure. AB - Patients with heart failure are known to demonstrate periodic respiration (PR) during sleep. The factors causing PR are not well known. We therefore studied 20 patients (aged 18-66 years) with idiopathic dilated cardiomyopathy. Full-night polysomnography and evaluation of respiration and transcutaneous oxygen saturation were performed. Hypercapnic ventilatory response (HCVR) was evaluated during daytime. The patients showed PR for 25 +/- 26% (mean +/- standard deviation) of total sleep time. During PR, oxygen desaturated 7.1 +/- 4.6%. Sleep was impaired. HCVR was normal. Oxygen desaturation during PR was predicted by HCVR (r = 0.47, P < 0.05) and left atrial diameter (r = 0.60, P < 0.05). The time period of PR expressed as a fraction of total sleep time was correlated with HCVR (r = 0.45, P < 0.05) and left atrial diameter (r = 0.51, P < 0.05). In conclusion, PR with oxygen desaturation, arousals, and impaired sleep was observed in stable heart failure. HCVR and left heart dimensions were related to PR. These findings confirm the concept of a feedback loop describing respiratory control in PR. PMID- 8471815 TI - Influence of fiber, xylitol and fructose in enteral formulas on glucose and lipid metabolism in normal subjects. AB - To verify the benefit of nonglucose carbohydrates and fiber in enteral formula diets we studied the postprandial metabolism of eight healthy subjects after the intake of two helpings (25 g carbohydrates each) of five commonly used enteral formulas over 4 h. There were no significant differences in postprandial concentrations of blood glucose among the formulas. The area under the curve of postprandial insulin values, however, was significantly smaller after consumption of the fructose-containing formula (1948 +/- 285 microU min ml-1, P < 0.05) than after fiber-free (3222 +/- 678 microU min ml-1) or two fiber-containing products (2664 +/- 326 microU min ml-1, P < 0.05; and 3040 +/- 708 microU min ml-1, P < 0.05). The insulin area of the xylitol-containing formula (2307 +/- 364 microU min ml-1) was significantly smaller compared to the fiber-free product (P < 0.05). In addition, we found the postprandial increase in triglycerides to be significantly higher after the xylitol-containing formula (from 0.93 +/- 0.14 to 1.25 +/- 0.22 mmol/l) than after the fiber-free product (from 0.82 +/- 0.13 to 0.97 +/- 0.16 mmol/l, P < 0.05) or the two fiber-containing products (from 0.88 +/- 0.16 to 0.96 +/- 0.18 mmol/l, P < 0.05; and from 0.80 +/- 0.08 to 0.95 +/- 0.10 mmol/l, P < 0.05). We conclude that a patient with type II diabetes may benefit from replacing glucose and glucose-equivalent carbohydrates with fructose or xylitol. PMID- 8471816 TI - Postoperative pulmonary complications in patients with esophageal cancer. AB - There are recent reports on postoperative pulmonary complications in patients with esophageal cancer who were treated preoperatively with chemotherapy and irradiation. The Hamburg Esophageal Study Group is currently undertaking a prospective randomized study to evaluate the efficacy of preoperative treatment. Postoperative pulmonary complications and mortality in these patients with either a combined preoperative treatment (group 1, n = 11) or chemotherapy alone (group 2, n = 9) are evaluated in the present paper. Complete remission of the tumor was found more often in group 1 (54.6%) than in group 2 (22.2%). However, postoperatively the patients of group 1 developed adult respiratory distress syndrome (ARDS; 54.6%) more frequently than in group 2 (11.1%), and all patients with ARDS died. Thus, although the combined preoperative treatment is more effective in tumor remission, it is associated with a higher respiratory failure and postoperative mortality. Therefore, the preoperative regime has now been changed by the study group. Since after the clinical manifestation of ARDS no causative clinical therapy is available up to now, attention must be focused on the prevention of respiratory failure. PMID- 8471817 TI - A novel variety of atypical Pneumocystis carinii infection after long-term prophylactic pentamidine inhalation in an AIDS patient: large lower lobe pneumocystoma. AB - Atypical pulmonary manifestations of Pneumocystis carinii infection and fair numbers of extrapulmonary and disseminated infections have lately been documented in patients with human immunodeficiency virus infection treated prophylactically with inhalative pentamidine. We report the case of a 32-year-old homosexual patient who was assessed for complaints of night sweats, weight loss, and progressive malaise. The patient denied any respiratory tract symptoms such as cough, sputum production, pleuritic chest pain, or shortness of breath. Chest X ray revealed two large round noncavitating lesions in the lower lobe of the right lung. Pneumocystomas were diagnosed by fine-needle aspiration. A 3-week course of intravenous high-dose cotrimoxazole resulted in amelioration of symptoms but no change in the radiographic appearance of the pulmonary lesions. Four months later the patient is alive and stable and is being treated with pentamidine inhalation of 300 mg per 2 weeks and two tablets of pyrimethamine sulfadoxine per week. PMID- 8471818 TI - Effects of fish oil concentrate on lipoproteins and apolipoproteins in familial combined hyperlipidemia. AB - The effects of two moderate doses of long-chain n-3 fatty acids (3.0 and 4.5 g EPA+DHA per day for 4 weeks each) on serum lipids and lipoproteins of patients with familial combined hyperlipidemia (FCH) were studied in a double-blind, placebo-controlled clinical trial. In nine patients with FCH n-3 fatty acids led to a statistically significant, dose-dependent fall in very low density lipoprotein (VLDL) triglycerides (3 g/day: -42%, 4.5 g/day: -55%) VLDL cholesterol (3 g/day: -41%, 4.5 g/day: -47%), and VLDL apolipoprotein (apo) B-100 (3 g/day: -40%, 4.5 g/day: -56%). No overall change in low-density lipoprotein (LDL) cholesterol was found, as confirmed statistically. However, when analyzing the data of single patients LDL cholesterol and LDL apo B did not change in five patients but increased dose dependently (from pretreatment 4.80 +/- 0.93 mmol/l to 5.70 +/- 0.93 mmol/l LDL cholesterol after 4.5 g/day) in four. LDL and VLDL composition as indicated by cholesterol/apo B-100 and triglyceride/apo B-100 ratios did not change significantly. High-density lipoprotein (HDL) cholesterol was unchanged; the HDL cholesterol/apo A-I+apo A-II ratio increased by 19% (P < 0.05) during fish oil treatment. We conclude that in FCH moderate doses of long chain n-3 fatty acids are highly effective in lowering pathological VLDL triglycerides, VLDL cholesterol, and VLDL apo B. LDL cholesterol must, however, be monitored during treatment as it may rise substantially in some although not in all patients with this disease. PMID- 8471819 TI - Chronic pentamidine aerosol prophylaxis does not induce QT prolongation. AB - Intravenous administration of pentamidine is known to cause long-QT syndrome (Torsade de pointes tachycardias and large QT prolongation) in rare cases and to cause small QT prolongation regularly. A similar pattern is seen with other drugs known to cause a long-QT syndrome. Pentamidine aerosol prophylaxis is commonly used to prevent Pneumocystis carinii pneumonia in HIV-infected persons. The goal of this study was to clarify whether pentamidine aerosol prophylaxis induces QT prolongation. We examined 100 patients receiving pentamidine aerosol prophylaxis at a rather high dose (300 mg biweekly) for at least 1 month (range 1-24) by determining the QT interval corrected for heart rate (QTc), blind for treatment. In a cross-sectional study, QTc was not different in 50 HIV-infected patients with chronic pentamidine aerosol prophylaxis (413 ms), 50 similar HIV-infected patients without pentamidine (407 ms), and 50 similar patients without HIV infection and without pentamidine (407 ms). In a longitudinal study in another 50 HIV-infected patients, QTc was the same before (414 ms) and on long-term (median 9-month) pentamidine aerosol prophylaxis (414 ms). In contrast to the case with intravenous pentamidine, we found no QT prolongation and thereby no risk of long QT syndrome with pentamidine aerosol prophylaxis. PMID- 8471820 TI - Efficacy and tolerance of recombinant tissue-type plasminogen activator in patients with thrombotic or embolic occlusions of leg-arteries. AB - The efficacy and safety of recombinant tissue-type plasminogen activator (rt-PA) was evaluated in 46 patients with thromboembolic arterial occlusions in leg arteries. rt-PA was given over 1-4 h with a maximum dose of 18 mg. The effect of rt-PA treatment was determined as patency of the occluded arteries in 44 different patients 14 days after treatment. In 41 patients at least one artery was recanalized (93%) by rt-PA, and in almost half of these patients (48%) no residual stenosis were detected after the lytic treatment. A slight residual stenosis was detected in 29% of the patients and a severe residual stenosis in 21%. An additional treatment with percutaneous transluminal angioplasty was performed in 23 of the 44 patients and successful in 21 (91%). In 8 patients an addition catheter-embolectomy was performed. No difference in patency rate was detected between patients with thrombotic and those with embolic occlusions. The age of the occlusion influenced the patency rate; occlusions under the age of 5 weeks showed a patency rate of 96% compared to 82% in older occlusions. The length of the occlusion did not have any influence on the outcome of the rt-PA treatment. From the results of this open study we conclude that a dose of up to 18 mg of rt-PA is both safe and effective in the treatment of thromboembolic occlusions in leg arteries. PMID- 8471821 TI - Selective intra-lysosomal concentration of niobium in kidney and bone marrow cells: a microanalytical study. AB - Niobium is used as an alloy in the industrial and biomedical fields. The concentration of the toxic element in organs of a number of animal species has been defined by using radioactive niobium (95Nb). However, tissue lesions induced by niobium have only been studied at the light microscopy level. In this study, we used an electron probe X-ray analyzer equipped with a transmission electron microscope to define the localization of this element in kidney and bone marrow cells. Results demonstrated that niobium is located in the lysosome and that this element coprecipitates with phosphate. In kidney, lysosomes and precipitates are eliminated in the tubular lumen. In contrast, precipitates appear to be eliminated more slowly from the lysosomes of bone marrow macrophages. These processes therefore correspond to one of the mechanisms by which lysosomes eliminate certain toxic mineral elements and thus play a role in the more general process of the body's defenses. PMID- 8471822 TI - Purification of outer membrane iron transport receptors from Escherichia coli by fast protein liquid chromatography: FepA and FecA. AB - Fast protein liquid chromatography (FPLC) with DEAE-Sepharose Fast Flow, PBE-94 and Q-Sepharose Fast Flow columns are applied to the purification of the ferric enterobactin protein receptor (FepA). The apparent single band of FepA on SDS PAGE is isolated and purified into two proteins with very similar molecular weights. The two proteins are identified to be FepA and ferric citrate protein receptor (FecA) by N-terminus amino acid determination and a computer search with the Gene Bank file. The assay of binding activities of these proteins shows that both FepA and FecA bind ferric enterobactin, with the former having about double the activity of the latter. Competition studies shows that Fe-MECAM is competitively bound to both proteins and that ferric parabactin only slightly competes with [55Fe]ferric enterobactin. It is found that ferrichrome A has no effect on the binding of the receptor proteins with ferric enterobactin. PMID- 8471823 TI - Effect of chronic vanadium administration in drinking water to rats. AB - Two-month old Wistar rats of both sexes received, as sole drinking liquid, an aqueous solution of ammonium metavanadate (AMV) at a concentration of 0.01 or 0.05 mg V cm-3 (0.2 or 1.0 mM) for a period of 4 weeks. It was calculated that the animals took up doses of 1.5 and 5-6 mg V kg body weight-1 24 h-1, respectively. Food and AMV solution consumption in the experimental group was similar to food and water consumption in the control group. A statistically significant decrease of consumption of AMV solution at a concentration of 0.05 mg V cm-3 was noted only in males. Hematological examination demonstrated a decrease in the erythrocyte count, hemoglobin level and hematocrit index. This decrease in the erythrocyte count was associated with an increased percentage of reticulocytes in the peripheral blood of the animals drinking the solution with a higher vanadium content. Biochemical analyses demonstrated a decrease of L ascorbic acid levels in the plasma and erythrocytes of animals drinking the AMV solutions. A distinct tendency for the malonyldialdehyde level to increase in the blood was also observed. Among the enzymes examined in the erythrocytes (catalase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase and delta aminolevulinic acid dehydratase [ALA-D]) only ALA-D activity was depressed. PMID- 8471824 TI - A novel purification of ferric citrate receptor (FecA) from Escherichia coli UT5600 and further characterization of its binding activity. AB - In our earlier paper, it was demonstrated that the FecA receptor protein from Escherichia coli UT5600/pBB2 (leu-, proC-, trpE-, entA-, rpsl-, delta (ompT-fepA) /Ampr, fepA) binds with ferric enterobactin. In order to explore this further the outer membrane receptor protein, FecA, has been isolated from UT5600 (fepA-) and purified to homogeneity by DE-52-cellulose anion exchange chromatography followed by MonoPFPLC chromatofocusing. Partially purified FecA and homogeneous FecA show binding activity to [55Fe]ferric enterobactin and the binding is specific. Binding activity of FecA can be enhanced by ferric citrate. Lipopolysaccharide free FecA as ascertained by silver staining and the endotoxin test still retains the same activity. In vivo uptake studies using different strains of E. coli suggest that FecA in E. coli plays an important role in ferrienterobactin transport. PMID- 8471825 TI - Metal resistance in Acinetobacter and its relation to beta-lactamase production. AB - Thirty nine clinical isolates of Acinetobacter belonging to six species were tested for resistance to 20 metal ions and their ability to produce beta lactamase. Fifty two percent of the strains produced beta-lactamase. beta Lactamase producers and non-producers were almost equally distributed in the different species. A. baumannii was the predominant biotype and was found to be most resistant to metals. Resistance to mercury was prevalent in beta-lactamase producing A. baumannii only. Silver resistant strains of A. baumannii produced beta-lactamase. Sensitivity and resistance to copper and cadium was equally distributed between beta-lactamase producers and non-producers. beta-Lactamase producer and -non-producer strains were uniformly sensitive to cadmium except Acinetobacter genospecies 1. PMID- 8471826 TI - Concentrations of heavy metals in maternal and umbilical cord blood. AB - Concentrations of lead, cadmium, methylmercury and total mercury were measured in maternal and umbilical cord blood using graphite atomic absorption spectrometry. Two essential metals, copper and zinc, were also determined using ion chromatography. Lead, copper and zinc were found to be lower in the cord blood whereas methylmercury and total mercury were higher in cord blood than in maternal blood. Little differences were noted for cadmium in maternal and cord blood. Significant positive correlations were observed between the concentrations in maternal and cord blood with regard to lead (correlation coefficient, r = 0.44), copper (r = 0.34), zinc (r = 0.29), methylmercury (r = 0.44) and total mercury (r = 0.58). These results suggest that, like essential metals, most heavy metals can move rather freely across the human placenta. The potential health effects of heavy metal transfer from mothers to young infants cannot be discounted. PMID- 8471828 TI - A single electroconvulsive treatment affects platelet serotonin uptake in bipolar I patients. AB - We evaluated serotonin (5HT) uptake parameters in platelets of a group of bipolar I patients in both a depressive phase and a mixed state, before (t0) and after (t1) the first electroconvulsive treatment (ECT). The results showed the presence of significant changes in the number of the carrier proteins for 5HT at t1, which in most cases preceded the clinical improvement. Although other mechanisms are certainly involved, these data suggest that ECT may influence the 5HT transport through platelet membranes. PMID- 8471827 TI - Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects. AB - We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean +/- SD micrograms/l) of fluvoxamine were 125 +/- 91 and 142 +/- 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 micrograms/l. Plasma concentrations (mean +/- SD micrograms/l) of maprotiline were 146 +/- 62 and 202 +/- 134 on days 8 and 28, respectively and the range of maprotiline plasma concentration on day 28 was from 12 to 428 micrograms/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of maprotiline were significantly (P < 0.05) associated with more side effects. PMID- 8471829 TI - Chloroquine-induced seizures in mice: the role of monoaminergic mechanisms. AB - The influence of some dopaminergic and noradrenergic agents on seizures induced by chloroquine (45-100 mg/kg, i.p.) was investigated in mice. Apomorphine (0.2 0.8 mg/kg, s.c.). L-dopa (25-50 mg/kg, s.c.) benserazide (5 mg/kg, i.p.) plus L dopa (50 mg/kg, s.c.), pargyline (100 mg/kg, i.p.), FLA-63 (10-20 mg/kg, s.c.) and FLA-63 (10 mg/kg, s.c.) plus L-dopa (50 mg/kg, s.c.) profoundly shortened the latency of seizures induced by chloroquine (65 mg/kg, i.p.). L-Dopa (50 mg/kg, s.c.) weakly reduced the latency and weakly increased the incidence of chloroquine (50 mg/kg, i.p.)-induced seizures. alpha-Methyl-p-tyrosine (25-100 mg/kg, i.p.) dose-dependently and significantly reduced the incidence and significantly prolonged the latency of chloroquine (65 mg/kg, i.p.)-induced seizures. However, L-dopa (50 mg/kg, s.c.) effectively increased the proportion of animals convulsing and effectively reduced the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in alpha-methyl-p-tyrosine-pretreated mice. Haloperidol (0.25-1.0 mg/kg, i.p.) and pimozide (2-4 mg/kg, i.p.) markedly reduced the incidence and markedly prolonged the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in a dose-related manner. However, apomorphine (0.4 0.8 mg/kg, s.c.) and L-dopa (25-50 mg/kg, s.c.) profoundly attenuated the protective effects of haloperidol (0.5 mg/kg, i.p.) and pimozide (4 mg/kg, i.p.) against chloroquine (65 mg/kg, i.p.)-induced seizures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471830 TI - The influence of lorazepam medication upon the transfer properties of the brain during sleep in man. AB - In order to get better insight into the principles of information processing by the brain during sleep and its alterations under the influence of drugs we applied some tools from linear system theory to sleep EEG data. We investigated late components of auditory and visually evoked potentials (AEPs and VEPs) during different sleep stages and calculated from these the so-called amplitude frequency characteristics (AFC). The main advantage of this analysis is that it enables one to detect functional differences during different sleep stages. This information can hardly be obtained by conventional spectral analysis. The result of our investigation was that the transfer properties of the brain during sleep were extremely different and that lorazepam medication not only resulted in quantitative alterations of the sleep profile but mainly in highly significant alterations of the functional properties of sleep. PMID- 8471831 TI - Anti-exploratory effect of N-methyl-D-aspartate in elevated plus-maze. Involvement of NMDA and CCK receptors. AB - N-Methyl-D-aspartate (NMDA, 20 mg/kg) produced a clear decrease in mouse exploration in open parts of an elevated plus-maze. Paradoxically, 40 mg/kg NMDA did not modify the behavior of the mice in the plus-maze. NMDA at a dose of 80 mg/kg again depressed the exploratory activity of mice, but this effect was accompanied with tremor and compulsive tail biting. The 'anti-exploratory' dose of NMDA (20 mg/kg) increased, whereas the 'tremorigenic' dose (80 mg/kg) significantly decreased the number of cholecystokinin (CCK) binding sites in the mouse cerebral cortex. The competitive NMDA antagonist (+/-)-CPP (2.5-5 mg/kg) and the non-competitive antagonist MK-801 (0.25 mg/kg) antagonized the anti exploratory effect of NMDA (20 mg/kg). The tricyclic antidepressant imipramine (5 mg/kg, but not 1 or 10 mg/kg) also attenuated the inhibition of exploratory activity induced by NMDA. Of three CCK receptor antagonists tested, the unselective CCK antagonist proglumide (1 mg/kg, but not 0.1 and 10 mg/kg) significantly opposed the anti-exploratory action of NMDA. The selective CCK antagonists L-365,260 (1 microgram/kg) and devazepide (1 microgram/kg) were evidently weaker antagonists of NMDA. Furthermore, 10 micrograms/kg of L-365,260, a CCK-B receptor antagonist, and 1 mg/kg of devazepide, a CCK-A receptor antagonist, even tended to augment the effect of NMDA in the plus-maze. The results of the present study seem to give some support to the notion that not only NMDA receptors, but also CCK-ergic mechanisms are involved in the modulation of anti-exploratory action of NMDA in the elevated plus-maze. PMID- 8471832 TI - Prolactin and thyrotropin responses to ECT after pindolol administration. A placebo controlled study. AB - The effect of pindolol, a beta-receptor blocker with potent 5-HT1 receptor antagonistic properties, on the prolactin (PRL) and thyrotropin (TSH) responses to electroconvulsive therapy (ECT) was systematically studied in 12 female depressed patients. In a balanced order, crossover design, the patients were given placebo or pindolol 5 mg orally, 1 h prior to bilateral ECT. The last five patients were additionally tested with 10 mg pindolol during the third ECT. Plasma levels of PRL and TSH increased in all three trials, but no consistent effect of pindolol on these hormonal responses could be demonstrated. Pindolol tended to attenuate seizure duration, especially at the 10 mg dose. The participation of 5-HT1 receptor activity in the secretion of PRL and TSH during ECT remains uncertain. PMID- 8471833 TI - The inheritance pattern of dysplastic naevi in families of dysplastic naevus patients. AB - Dysplastic naevi (DN) are the major precursor lesions of malignant melanoma, yet the presumed mode of inheritance or genetic aetiology of DN remains controversial. The inheritance pattern of DN in families from a randomly selected population of 26 dysplastic naevus patients was investigated by estimating the segregation ratio in families ascertained through an offspring with DN (incomplete ascertainment). For families ascertained through a parent with DN (complete ascertainment) the transmission pattern was examined by comparing the observed number of affected offspring to the expected number using a chi 2 goodness-of-fit test. Results from the chi 2 tests and the estimated segregation ratio of 0.52 (95% confidence interval: 0.31, 0.73) suggest that the inheritance pattern for dysplastic naevi in these families is consistent with autosomal dominant transmission, although the present study was limited because of a small sample size. The findings, therefore, need to be confirmed by a much larger study that is able to test more rigorously specific genetic hypotheses. PMID- 8471834 TI - Expression of the c-ski proto-oncogene in human melanoma cell lines. AB - The aim of this study was to establish whether the expression of proto-oncogene c ski in melanoma might be related to alterations of chromosome 1q involving the native location of the gene. Six melanoma cell lines, including two carrying marker chromosomes derived from breakage at 1q12-q21, were studied. Expression of c-ski was observed in all cell lines, with very high levels in five of them. However no alteration in c-ski structure or dosage was found in any of the melanoma cell lines, including those with non-random breakpoints near the gene. c ski Transcripts were detected in cell cultures from normal melanocytes, but at a much lower level than that observed in melanoma cell lines. Transcripts of c-myb and the beta-NGF gene were not detectable in any of the melanoma cell lines, whereas sis- and epidermal growth factor (EGF) receptor gene-specific transcripts were present in two and four melanoma cell lines, respectively. The constant expression of c-ski in the melanoma-derived cell lines at a level of expression much higher than that of normal melanocytes suggests that this proto-oncogene may play a role in melanocyte transformation. PMID- 8471835 TI - Direct correlation between MUC18 expression and metastatic potential of human melanoma cells. AB - The expression of the glycoprotein MUC18 in melanoma biopsies has previously been shown to increase with increasing tumour thickness, and thus to correlate with the probability of metastasis development. We have examined the expression of this molecule by nine human melanoma cell lines with known metastatic ability (both spontaneous and experimental) in nude mice. Examination of the expression of both the MUC18 mRNA and of the glycoprotein on the cell surface revealed a statistically significant correlation (P = 0.040) between its expression and the ability to form metastases in vivo. Although MUC18 shows sequence similarity to neural cell adhesion molecules, no correlation was observed between the site of origin of the metastatic lesions (brain, lymph node) and MUC18 expression. PMID- 8471836 TI - Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma. AB - Fifteen patients with tumour recurrence following radical surgical excision of malignant melanoma were treated with a combination of interferon alpha-2a (rIFN alpha-2a) and interleukin-2 (rIL-2). Immunological monitoring (performed prior to therapy and on days 7, 21, and 28, of each course of treatment) showed significant changes of several parameters after rIFN alpha-2a and rIL-2 administration. A significant increase in cells expressing CD16 (cells bearing Fc receptor), CD25 (cells bearing IL-2 receptor), and CD56 (NK cells, activated lymphocytes), as well in levels of soluble IL-2 receptor, beta 2-microglobulin and neopterin was observed. Immunological changes were closely related to the injection of the biological agent and were more relevant during the first than the second cycle of treatment. rIFN alpha-2a and rIL-2 exerted a clear synergistic activity on the same immunological parameters. No major response was seen with the present approach: four subjects showed rapid progression of decrease during the first month of therapy, while of 11 patients who completed two courses of treatment, only five were considered in stable disease. In conclusion, our results suggest that a combination of rIFN alpha-2a and rIL-2, at dosages and schedules, used in this trial, was well-tolerated and immunologically active, but was clinically ineffective in the management of advanced melanoma. PMID- 8471837 TI - Increased spontaneous mutation rates and prevalence of karyotype abnormalities in highly metastatic human melanoma cell lines. AB - Previous studies have suggested that increased malignant potential might be related to increased genomic instability, but this issue still remains controversial. We tested this hypothesis in a human tumour spontaneous metastasis model, using six clones and variants isolated from the parental poorly metastatic M4Be melanoma cell line, and expressing various metastatic abilities. The spontaneous rates of mutation to ouabain resistance measured in these cells by Luria and Delbruck fluctuation analysis correlated with the metastatic ability of the cells: moderately and highly metastatic cells showed spontaneous mutation rates 10 to 50 times higher than those of poorly metastatic cells. Genomic instability at the chromosome level was assessed by searching for accumulated structural abnormalities in the moderately and highly metastatic cell lines. All the cell lines appeared hypertriploid, and showed comparable modal numbers and great chromosome dispersion. Unstable DNA amplification in the form of double minute chromosomes was shown in one of the four poorly metastatic cell lines, and in a significantly higher proportion of the cells of two of the three metastatic cell lines. Abnormal chromosomes were demonstrated in all cell lines, with markers involving specific rearrangements of chromosomes 1, 6, 7, 8, 9, 11, 14 and 15, as frequently observed in human melanoma cells. Clonal markers were present in all cell lines, documenting the common origin of all variants and clones, and specific marker amplification was noticed in highly metastatic cells compared to poorly metastatic lines. These results suggest that human tumour progression might be accompanied both by an increase in genomic instability and by accumulation of karyotypic abnormalities. PMID- 8471838 TI - Characterization of cellular infiltration in choroidal melanoma. AB - An immunohistochemical double staining technique was used to examine the characteristics of cellular infiltration in choroidal melanoma. Seven of 16 melanomas examined demonstrated high levels of cellular infiltration, mainly with T-cells and macrophages, and little infiltration with B-cells and NK cells. The majority of T-cells were of the CD8+ type and were activated, as shown by the expression of histocompatibility antigens, HLA-DR and IL2-R. Most of the infiltrating macrophages also expressed HLA-DR antigen. We also detected malignant melanocytes expressing the HLA-DR antigen. This technique could be used to study in detail cellular infiltration in a large number of archival choroidal melanomas with known clinical history, which would enable detection of markers that correlate with the prognosis of the disease. PMID- 8471839 TI - Inhibition of melanoma cell/matrix interaction by tamoxifen. AB - Following our recent finding that calmodulin antagonists can reduce cancer cell attachment to extracellular matrix proteins, we investigated the calmodulin antagonistic and anti-attachment properties of the non-steroidal anti-oestrogens tamoxifen and droloxifene. These drugs and four of their active metabolites were found to have calmodulin antagonist activity with IC50 values of 2-4 microM and to be capable of inhibiting attachment of murine B16 melanoma to extracellular matrix proteins in vitro. IC50 values for inhibition of attachment were 11 microM for tamoxifen and ranged from 5 to 40 microM for the other five compounds tested. (Poor reproducibility in drug potency between attachment experiments was almost certainly due to the low aqueous solubility of these drugs.) The effects of tamoxifen on cell/matrix adhesion were most evident between 15 min and 3 h of cell attachment. No effects of tamoxifen were evident in cells which had been allowed to attach for 6 h or more. Tamoxifen at concentrations between 0.1 and 30 microM was without effect on intracellular free calcium concentration. Tamoxifen also inhibited attachment of human ocular melanoma cells and human breast cancer (MCF7) cells to type I collagen. The concentration at which tamoxifen and its metabolites affect cell attachment in vitro (2-14 microM) is of the same order as the tissue concentrations of these drugs achieved clinically. The possibility exists that reduction of cell/matrix interactions may contribute to the clinical anti-metastatic efficacy of tamoxifen and some of its active metabolites. PMID- 8471840 TI - Melanoma as a macrophage/melanocyte hybrid and the symbiotic nature of eukaryotic cells. PMID- 8471841 TI - Melanoma, vitiligo and topographic antigens. PMID- 8471842 TI - European Organization for Research and Treatment of Cancer (EORTC)-Melanoma Cooperative Group (MCG) meeting. Lyon, France, 6-7 November 1992. PMID- 8471843 TI - Expression and single-step purification of enzymatically active vaccinia virus thymidine kinase containing an engineered oligohistidine domain by immobilized metal affinity chromatography. AB - A method has been developed for the controlled expression in Escherichia coli and rapid purification of an enzymatically active vaccinia virus (VV) thymidine kinase protein containing an engineered oligohistidine domain. The nucleotide sequence that encodes the VV thymidine kinase open reading frame was inserted into a plasmid expression vector (pET-16b, Novagen Inc., Madison, WI) under the control of a strongly repressed bacteriophage T7 promoter and high efficiency translational signals. The construct (pET-16b:TK) directs the synthesis of a fusion protein (His-TK) with an N-terminal histidine decapeptide fused to the VV thymidine kinase polypeptide. Upon induction of E. coli strain BL21(DE3)pLysS with isopropyl beta-D-thiogalactoside, accumulation of large quantities of a 22 kDa protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein reacted with polyclonal antiserum raised against a TrpE-VVTK fusion protein. The predominantly soluble fusion protein (approximately 13% of the total soluble bacterial protein) was purified to homogeneity from crude bacterial extracts in a single-step by immobilized metal chelate affinity chromatography (Ni(2+)-nitrilotriacetic acid-agarose) under nondenaturing conditions and was shown to have thymidine kinase activity. The yield of the purification scheme was about 15 mg recombinant protein/liter of bacterial culture. The availability of purified VV TK protein should greatly facilitate biochemical studies on its enzymatic activity, as well as analyses of its structural and functional domains. PMID- 8471844 TI - One-step chromatographic method for the purification of avian serotransferrin. AB - Existing purification procedures for serum transferrins involve multistep chromatographic separations and require several days to complete. In addition, they have not been tested for purification of transferrins directly from the blood of egg-laying animals, where large amounts of circulatory lipoproteins can interfere with standard chromatographic separations. We have developed a procedure for purifying transferrin in one step directly from the serum of ovulating chickens. The method, which is based on hydrophobic interaction chromatography, gives a yield of about 12 mg (80%) of purified serotransferrin from 3 ml of serum and can be completed in a few hours. PMID- 8471845 TI - Characterization and N-terminal amino acid sequences of beta-(1-4)endoxylanases from Streptomyces roseiscleroticus: purification incorporating a bioprocessing agent. AB - Streptomyces roseiscleroticus produces extracellular xylanases when cultured on a liquid xylan medium. Purified xylanases are used to facilitate bleaching of kraft pulps in the pulp and paper industry. Downstream processing and purification of xylanases from S. roseiscleroticus is difficult unless red pigments produced by the bacterium are removed. We report that the bioprocessing agent, Biocryl BPA 1000, removes these pigments allowing purification of four xylanases by HPLC employing cation exchange, hydrophobic interaction, and gel filtration. The xylanases have been named Xyl1, Xyl2, Xyl3, and Xyl4 according to their order of elution from the cation exchange column. The purified xylanases have been characterized according to their molecular weights, pH and temperature stabilities, N-terminal amino acid sequences, and hydrolysis action patterns on oat spelt xylan. The molecular weights by mass spectroscopy for Xyl1-Xyl4 are 33,647, 33,655, 21,070, and 46,855, respectively. All four xylanases exhibit pH optima between 5.0 and 7.0 and temperature optima between 50 and 60 degrees C. The N-terminal amino acid sequences are compared to sequences from Streptomyces lividans, Streptomyces 36A, and a Chainia sp. The N-terminal amino acid sequence of Xyl1 appears to be unique, but sequences from Xyl2, 3, and 4 bear strong homology to xylanases cloned from S. lividans. Xyl3 is also homologous to xylanases from Streptomyces 36A, and a Chainia sp. Predominant products of arabinoxylan hydrolysis by the purified xylanases included xylotriose, tetraose, and pentaose. None of the xylanases purified from S. roseiscleroticus produced xylose. PMID- 8471846 TI - Recombinant human transforming growth factor-beta 1: expression by Chinese hamster ovary cells, isolation, and characterization. AB - A partial cDNA clone encoding the gene for human transforming growth factor-beta 1 (TGF-beta 1) was isolated from a human bladder carcinoma cell line (5637) cDNA library. Following restriction enzyme processing and ligation of synthetic oligonucleotide linkers, the gene was inserted into a plasmid and transfected into Chinese hamster ovary cells. Clonal selection and growth conditions resulted in a method for production of recombinant human TGF-beta 1 at 7 mg/liter in conditioned cell medium. Through a combination of low pH treatment, cation exchange chromatography, and salt precipitation, the recombinant human TGF-beta 1 was purified in milligram amounts to > 95% purity in a yield of about 36%. Purification to homogeneity was accomplished by chromatography on C18 silica gel. Amino acid analysis, N-terminal sequencing, and growth inhibition assays indicate identity with the molecule from human platelets. PMID- 8471847 TI - The expression of hemolytically active human complement protein C9 in mammalian, insect, and yeast cells. AB - The cDNA sequence encoding mature human C9 protein and its signal peptide was cloned into three expression vectors for expression in COS-7 (mammalian), Spodoptera frugiperda IPLB-SF-21AE (insect), and Saccharomyces cerevisiae (yeast) cells. In addition, C9 cDNA encoding only the mature protein was fused to the yeast invertase leader sequence (SUC2) and cloned for expression in yeast. Under optimal conditions COS-7 and IPLB-SF-21AE cells secreted recombinant C9 (rC9) at concentrations of about 111 and 700 ng C9/ml culture supernatant, respectively. By comparison S. cerevisiae, whether transformed with C9 cDNA containing its native or yeast invertase leader sequence, secreted only very small amounts of rC9 (5-10 ng/ml). However, upon lysis concentrations of up to 500 ng/mg dry wt were found in yeast cells transformed with C9 cDNA. SDS-PAGE followed by Western blot analysis revealed COS-7 cell and S. cerevisiae expressed rC9 to have a MW similar to that of native C9 purified from human serum, while rC9 from IPLB-SF 21AE cells was about 4 kDa smaller. No hemolytic activity of S. cerevisiae secreted rC9 could be detected and the specific hemolytic activity of S. cerevisiae intracellular rC9 was also very low. However, the specific hemolytic activities of COS-7 and IPLB-SF-21AE secreted rC9 were indistinguishable from that of purified native human C9. Thus, for future studies on the structure and function of C9 where the production of large quantities of mutant protein would be desirable, the baculovirus-insect cell expression system appears to offer considerable advantages. PMID- 8471848 TI - Overcoming inclusion body formation in a high-level expression system. AB - Attempts at overexpressing T4-phage deoxycytidylate deaminase using the pET3c/BL21(DE3)/pLysS system resulted in this enzyme being part of an inactive inclusion-body complex. However, by employing an enriched growth medium it was found that the deaminase could be induced in a soluble active form to at least 20% of this organism's cellular protein. Insoluble inclusion bodies were obtained with less rich media. This procedure was employed successfully with other highly expressed proteins that formed inclusion bodies. The use of a rich growth medium during the course of protein induction may be a valuable adjunct to limiting inclusion body formation with this as well as other expression systems. PMID- 8471849 TI - Characterization of a truncated form of recombinant porcine growth hormone generated in vitro during solubilization of inclusion bodies. AB - During the development of a novel solubilization procedure (1) for bacterial inclusion bodies (IB's) using the cationic surfactant cetyltrimethylammonium chloride (CTAC; (CH3)3-N(+)-C16H33Cl) significant proportions of an apparently truncated, lower molecular weight (MW) variant form of recombinant pig growth hormone (rPGH) were observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis relative to pig pituitary derived GH. The formation of this rPGH like species, designated P-band, was found to occur in vitro during solubilization of IB's by CTAC and was dependent on pH and temperature of solubilization, but was not due directly to the use of CTAC, as purified soluble rPGH of the correct MW could not be converted to P-band by exposure to CTAC alone. The bacterial proteolysis suspected as being responsible for the in vitro formation of P-band could not be inhibited by the use of a "cocktail" of defined antiproteolytic agents but was inhibited by pH and temperature, and by solubilization of IB's in 5% SDS, 6 M gnHCl or 7.5 M urea. Detailed characterization of the structure of P-band by N-terminal amino acid sequencing, electrospray mass spectrometry, radioreceptor binding assay, peptide mapping, and C-terminal peptide sequencing confirmed that P-band was approximately 950 mass units smaller than normal rPGH and lacked eight C-terminal amino acids. A significant finding was that P-band is unable to bind to the pig liver-membrane GH receptor in a competitive radioreceptor assay. Analysis of the relative secondary and tertiary structure of P-band by circular dichroism spectra, intrinsic tryptophan-dependent fluorescence, and average surface hydrophobicity (2) suggested small but measurable changes to the overall structure of P-band relative to normal rPGH. Consequently, our results also suggest that the C terminal portion of rPGH, including in particular the last eight amino acids, is of major importance in the binding of rPGH to the pig liver membrane GH receptor. PMID- 8471850 TI - Methods of analysis for toxic elements in foods. Part IV. General method of ashing for the determination of toxic elements. AB - As a result of the request of the Codex Alimentarius Committee on Methods of Analysis and Sampling, a general method for ashing of foods for the determination of toxic elements was assembled. This method consolidates the results of more than a decade of interlaboratory work of numerous USSR food laboratories and specifies the details of wet and dry ashing procedures. PMID- 8471851 TI - New metrological characteristics of analytical methods of analysis used for safety control of food and environmental materials. AB - MQS and MQSm are new metrological characteristics of the limit of determination of methods used for safety control of foods and environmental objects. MQS is the minimum quantity of an analyte that can be determined by any applicable method in an analytical sample. MQSm is the minimum quantity of analyte that can be measured in the test solution in an interlaboratory, method-performance study of a specific method, under the condition that MQSm < or = MQS. Examples are given of their calculation and use. PMID- 8471852 TI - Determination of acesulfam-K in foods. AB - A liquid chromatographic method was evaluated for the determination of the intense sweetener acesulfam-K in tabletop sweetener, candy, soft drink, fruit juice, fruit nectar, yogurt, cream, custard, chocolate, and biscuit commercial preparations. Samples are extracted or simply diluted with water and filtered. Complex matrixes need a clarification step with Carrez solutions. An aliquot of the extract is analyzed on a reversed-phase mu Bondapak C18 column using 0.0125M KH2PO4 (pH 3.5)-acetonitrile (90 + 10) as mobile phase. Detection is performed by UV absorbance at 220 nm. Recoveries ranged from 95.2 to 106.8%. With one exception, all analyzed values were within +/- 15% of the declared levels. The repeatabilities and the repeatability coefficients of variation were, respectively, 0.37 mg/100 g and 0.98% for products containing less than 40 mg/100 g acesulfam-K and 2.43 mg/100 g and 1.29% for other products. The same procedure also allowed detection of many food additives or natural constituents, such as other intense sweeteners, organic acids, and alkaloids, in a single run without interfering with acesulfam-K. The method is simple, rapid, precise, and sensitive; therefore, it is suitable for routine analyses. PMID- 8471853 TI - Determination of aspartame and its major decomposition products in foods. AB - A liquid chromatographic procedure already evaluated in a preceding study for the analysis of acesulfam-K is also suitable for the determination of the intense sweetener aspartame in tabletop sweetener, candy, fruit beverage, fruit pulp, soft drink, yogurt, cream, cheese, and chocolate preparations. The method also allows the determination of aspartame's major decomposition products: diketopiperazine, aspartyl-phenylalanine, and phenylalanine. Samples are extracted or diluted with water and filtered. Complex matrixes are centrifuged or clarified with Carrez solutions. An aliquot of the extract is analyzed on a reversed-phase muBondapak C18 column using 0.0125M KH2PO4 (pH 3.5)-acetonitrile ([85 + 15] or [98 + 2]) as mobile phase. Detection is performed by UV absorbance at 214 nm. Recoveries ranged from 96.1 to 105.0%. Decomposition of the sweetener was observed in most food samples. However, the total aspartame values (measured aspartame + breakdown products) were within -10% and +5% of the declared levels. The repeatabilities and the repeatability coefficients of variation were, respectively, 1.00 mg/100 g and 1.34% for products containing less than 45 mg/100 g aspartame and 4.11 mg/100 g and 0.91% for other products. The technique is precise and sensitive. It enables the detection of many food additives or natural constituents, such as other intense sweeteners, organic acids, and alkaloids, in the same run without interfering with aspartame or its decomposition products. The method is consequently suitable for quality control or monitoring. PMID- 8471854 TI - Organochlorine pesticide residues in dairy milk in and around Delhi. AB - A survey of dairy milk and milk products in and around Delhi, India, was undertaken to monitor the levels of DDT and HCH. The survey revealed that pesticide residue levels in milk often exceeded the limits recommended by the Food and Agriculture Organization/World Health Organization Expert Committee. Maximum residue levels of total HCH in milk (fat/whole milk basis) has not yet been prescribed. The 15 samples of dairy milk and 4 samples of milk products analyzed had residue levels ranging from 0.022 to 0.166 micrograms/g for HCH and from 0.042 to 0.382 micrograms/g for DDT. PMID- 8471855 TI - Liquid chromatographic determination of 2-chloro-4-nitroaniline, 2-naphthol, and 2,4-dinitroaniline in D&C red no. 36. AB - A method is described for the determination of the intermediates and a related impurity in D&C Red No. 36 by reversed-phase liquid chromatography. This method may be used to ensure that limits set forth in the Code of Federal Regulations on the amounts of these 3 impurities in the color are not exceeded. The pigment is dissolved in boiling dioxane and then precipitated. The filtrate is chromatographed by isocratic elution, and then the column is washed and reequilibrated. Impurities were identified as 2-chloro-4-nitroaniline (2-Cl-4 NA), 2-naphthol, and 2,4-dinitroaniline (2,4-DNA) by comparison of their retention times and spectra with those of standards. Peak area calibrations were linear to at least 0.375% 2-Cl-4-NA, 1.25% 2-naphthol, and 0.025% 2,4-DNA, all with zero intercepts. At the specification levels, 99% confidence limits were 0.30 +/- 0.006% for 2-Cl-4-NA, 1.0 +/- 0.03% for 2-naphthol, and 0.020 +/- 0.0004% for 2,4-DNA. The limits of determination calculated from calibration data were 0.019% for 2-Cl-4-NA, 0.10% for 2-naphthol, and 0.0014% for 2,4-DNA at the 99% confidence level. Recoveries were 100-104% for 2-Cl-4-NA added to purified D&C Red No. 36, 100% for 2-naphthol, and 100-110% for 2,4-DNA; relative standard deviations were 0.8-3.4%. A survey of certified D&C Red No. 36 samples showed that the batches contained higher levels of intermediates than were determined previously by a cellulose column method in which the pigment was not dissolved. PMID- 8471856 TI - Automated technique for sampling milk from farm bulk tanks: collaborative study. AB - An automated, in-line, mechanical technique for sampling milk from farm bulk tanks was evaluated in a collaborative study. The automated sampling device, which is mounted on the milk intake line, contains an electronically controlled peristaltic pump. The device takes a representative sample of the entire volume pumped through the system. Samples taken can be analyzed for both composition and microbiological quality. The study was performed in 3 phases. In the first 2 phases, samples taken by manual and automated methods were compared in analyses for somatic cell count, antibiotics, fat, protein, lactose, and solids-not-fat. The third phase, using a modified procedure, was designed to compare sampling methods in analyses for total bacteria count (standard plate count), psychrotrophic bacteria count, and coliform count. Evaluation of the data by a nested ANOVA indicated no difference between results for samples taken by the automated and manual methods (P = 0.05) in Phases 1 and 2, irrespective of whether the bulk milk was agitated before sampling. By introducing a sanitizing step between farms in Phase 3, the automated method also provided samples comparable with those taken manually for microbial analyses. The automated method has been adopted first action by AOAC International. PMID- 8471857 TI - Analysis of testosterone esters by tandem mass spectrometry. AB - The electron ionization (EI) and chemical ionization (CI) mass spectra of 12 representative testosterone esters were examined to explore the various analytical options available for identification and confirmation of the esters. Using EI, a number of fragment ions indicated the identification of the testosterone moiety, but structural confirmation of the individual esters often required the observance of the molecular ion at very low relative abundance ratios. The acceptable analytical method involved CI/tandem mass spectrometry based on the production of the 2 generic product ions derived from the protonated molecule ion. PMID- 8471858 TI - Simultaneous determination of multiple tetracycline residues in milk using metal chelate affinity chromatography. AB - A method was developed for the determination of 7 tetracyclines in milk. Raw milk samples are defatted, acidified, and centrifuged to remove proteins, and the tetracyclines are specifically absorbed from the milk by chelation with metal ions bound to small Chelating Sepharose Fast Flow columns. The tetracyclines are removed from these columns with EDTA-containing buffer, and the extracts are further cleaned up by centrifugal ultrafiltration. Finally, the extracts are concentrated and analyzed simultaneously by on-line concentration. This method has limits of detection for individual tetracyclines of < 5 ng/mL and was validated with fortified milk samples at 15, 30, and 60 ng/mL. Recoveries exceeded 60% for all tetracyclines at all levels, with good precision. The method was also tested on milk from cows dosed with each of the tetracyclines. Advantages of this method over existing methods include its sensitivity, minimal use of organic solvents, and speed; with an autosampler, at least 14 samples can be processed and analyzed in 1 day. PMID- 8471859 TI - Quantitation of sulfamethazine in pork tissue by thin-layer chromatography. AB - Our earlier method to detect and quantitate sulfamethazine (SMZ) in milk at the 10 ppb level was modified to quantitate SMZ in pork tissue. Sulfabromomethazine (SBZ) is added to the tissue as an internal standard. SMZ and SBZ are extracted from the tissue into water as the supernatant of a centrifuged, aqueous homogenate and are cleaned up and concentrated by a series of solid-phase extractions. The sulfonamide-containing eluate is then separated on a silica gel thin-layer chromatographic plate. SBZ and SMZ are derivatized with fluorescamine, and their fluorescence is quantitated with a scanning densitometer. The limit of detection was estimated at 0.25 ppb (signal-to-noise ratio, 3:1). The average accuracy over the analysis range (0.54-21.8 ppb [micrograms/kg]) was 95.6% (standard deviation = 29.4%, n = 54). PMID- 8471860 TI - Liquid chromatographic detection of a variety of inexpensive sweeteners added to pure orange juice. AB - Liquid chromatography with pulsed amperometric detection was used to analyze pure orange juice adulterated with a variety of inexpensive sweeteners. This method can be used to detect low levels (5-10%) of high fructose corn syrup (42 and 55), cane sugar hydrolysates (50 and 80%), and beet sugar hydrolysates (chemically or enzymatically prepared). PMID- 8471861 TI - Evaluation of microbial loads of Bacillus subtilis spores on penicylinders. AB - Three types of penicylinders were compared for their retention of spores of Bacillus subtilis testing for sporicidal activity of disinfectants. Glass, porcelain, and stainless steel penicylinders are inoculated with a water suspension of B. subtilis var. niger (ATCC 9372) spores and dried. One set of each type of penicylinder is submerged 1 h in 0.9% saline. One set of porcelain penicylinders is submerged 15 h in a neutralized chemical germicide, and one set is also inoculated with a culture filtrate of B. subtilis (ATCC 19659), dried according to the AOAC method, and submerged 1 h in 0.9% saline. Microbial loads simulate those held on carriers used to test sporicidal activity of disinfectants. Carriers are immersed in chemical germicide, transferred to a neutralizer, and placed in a culture medium. Average percentages of B. subtilis var. niger spores retained on 10 carriers after 1 h submersion in saline and in water were as follows: glass, 93.6%; porcelain, 99.9%; and stainless steel, 99.5%. Retention of spores after 15 h submersion in a neutralized chemical germicide and in water was 98.9%. Porcelain penicylinders inoculated from a culture filtrate of B. subtilis (ATCC 19659) retained 26% of the spores after being submerged 1 h in saline and placed in water. Glass penicylinders, which retained the lowest and most variable number of spores, were the least suitable for sporicidal activity testing. B. subtilis (ATCC 19659) spores tested on porcelain penicylinders met only the minimum HCl resistance requirements of > or = 2 min. On porcelain penicylinders, the resistance of B. subtilis var. niger spores to 2.5N HCl was relative to the number of spores inoculated. PMID- 8471862 TI - Development of enzyme immunoassay for captan and its degradation product tetrahydrophthalimide in foods. AB - A simple, sensitive, and precise enzyme-linked immunosorbent assay (ELISA) is described for the quantitation of captan as its degradation product tetrahydrophthalimide (THPI) in foods using polyclonal antibodies. Three hapten analogues of THPI with different alkyl spacer arm lengths were synthesized. Immunogens and coating proteins were prepared by coupling these haptens to human serum albumin and ovalbumin, respectively. A 5-carbon spacer arm appeared to be optimum for the production of antibodies. Heterologous coating proteins did not improve the sensitivity, but reduction of homologous coating protein concentration did improve the sensitivity, resulting in a concentration of test compound required to inhibit binding by 50% of 15.5 ng/mL. The antiserum is specific for captan, captafol, and THPI, but not other structurally related compounds. The minimum detection limit was 1 ng/mL; the linearity was 1-200 ng/mL. The overall recoveries of captan and THPI from 11 commodities spiked at 4 levels were 92 and 100%, respectively. The intra-assay and interassay coefficients of variation were 9.1 and 16.8% for apple blanks and 5.9 and 4.2% for apple spiked with 3 ppm THPI, respectively. The ELISA described is suitable for measuring captan and THPI at levels comparable to those typically found in fruit. PMID- 8471864 TI - Niacin. I: Dissolution profiles of sustained-release niacin products by automated and manual procedures. AB - Automated and manual procedures were developed to obtain dissolution profiles of sustained-release niacin formulations. The procedures are based on the United States Pharmacopeia XXII apparatus 1 (basket) at 100 rpm with 900 mL 0.1N HCl as the dissolution medium. Filtered aliquots are read at 260 nm. No interference was found from excipients. The procedures are straightforward and will discriminate between sustained-release and regular niacin formulations. PMID- 8471865 TI - Analysis of milk-based infant formula. Phase V. Vitamins A and E, folic acid, and pantothenic acid: Food and Drug Administration-Infant Formula Council: collaborative study. AB - In 1982, the U.S. Food and Drug Administration, the Infant Formula Council and its member companies, contract laboratories, and other government laboratories began a study of analytical methods for the nutrients listed in the Infant Formula Act of 1980 (P.L. 96-359). Four phases of the study have been completed and are discussed in earlier reports. The present report provides data on Phase V, in which 13 laboratories collaboratively studied individual methods for folic acid, pantothenic acid, and vitamin E, in addition to 2 methods for vitamin A. Vitamins A and E are determined by liquid chromatography. Folic acid and pantothenic acid are determined by microbiological methods using acidimetric and/or turbidimetric assays as the determinative step. In most cases, relative standard deviations for repeatability, RSDr, and reproducibility, RSDR, are as good as those that would be predicted from other collaborative studies. RSDr and RSDR values obtained for the 5 methods are 9.35 and 25.44% for folic acid, 4.59 and 10.23% for pantothenic acid, 8.46 and 11.69% for vitamin E, 3.62 and 9.72% for vitamin A (retinol isomers), and 4.9 and 10.5% for vitamin A (retinol). The 5 methods have been adopted first action by AOAC International. PMID- 8471863 TI - Liquid chromatographic analysis of niacin in fortified food products. AB - An ion exchange liquid chromatographic (LC) method using an anion exchange resin column was developed for the determination of niacin in fortified foods. Samples were extracted by autoclaving with H2SO4 (1 + 1). Florisil open column chromatography was used to remove interferences from the sample extracts. Niacin levels were quantitated by an LC system using a 250 x 4.1 mm Hamilton PRP-X100 column, a mobile phase of 2% glacial acetic acid in water, and UV detection at 254 nm. The limit of detection was 0.11 micrograms niacin/mL, and the standard curve was linear from 0.24 to 0.80 micrograms niacin/mL. The system reproducibility was evaluated by completing 10 repetitive analyses on an infant formula and a macaroni product, which gave an average CV of 2.7%. Mean recovery (+/- standard deviation) was 99.8 +/- 7.7 (n = 15). The results compared favorably with those by the AOAC microbiological method. PMID- 8471866 TI - Comparison of liquid chromatographic method to AOAC microbiological method for determination of L-tryptophan in tablets and capsules. AB - A reversed-phase liquid chromatographic (LC) method coupled with precolumn derivatization of L-tryptophan with phenylisothiocyanate was compared to the AOAC microbiological method for determining L-tryptophan in tablets and capsules. For the microbiological method, the concentrations of L-tryptophan were 4-8% lower in autoclaved test samples (hot method) than in test samples that were not autoclaved (cold method). When L-tryptophan values obtained by the LC method were compared to those obtained by the cold microbiological method, no significant differences were observed (P > 0.05). The mean relative standard deviations were 2.9% for the LC method and 1.6% for the cold microbiological method. The mean recoveries of standard L-tryptophan added before analysis were 99% for the LC method and 101% for the cold microbiological method. These results demonstrate that both methods are reliable for determining free L-tryptophan contained in tablets and capsules. However, the LC method has the advantages of using a smaller test portion and having a shorter analysis time. PMID- 8471867 TI - Sample preparation bias in carbon stable isotope ratio analysis of fruit juices and sweeteners. AB - Two sample preparation methods are commonly used for carbon stable isotope ratio analysis (SIRA). One involves combustion of the sample with oxygen at 850 degrees C; the other involves combustion of the sample with CuO in an evacuated glass tube at 550 degrees C. I observed in our laboratory that these 2 methods yield different results for sugar-based products such as fruit juices, sweeteners, and vanillin. The CuO method yields results approximately 1%. more positive than the oxygen combustion method. This bias is also observed in other laboratories, as shown in an analysis of the results of the AOAC collaborative studies of carbon SIRA of maple syrup, orange juice, honey, and honey protein. The oxygen combustion method is the AOAC method for honey, apple juice, and orange juice; both methods are incorporated into the AOAC method for maple syrup. I recommend that data generated by the CuO combustion method be appropriately corrected to yield results concordant with the official oxygen combustion method. PMID- 8471868 TI - Liquid chromatographic determination and liquid chromatographic-thermospray mass spectrometric confirmation of nicarbazin in chicken tissues: interlaboratory study. AB - The U.S. Food and Drug Administration sponsored an interlaboratory study of a liquid chromatographic determination with ultraviolet detection of nicarbazin in chicken liver and muscle tissues. The method determined the 4,4' dinitrocarbanilide (DNC) portion of nicarbazin. The interlaboratory study of the determinative method was successful for nicarbazin at the 4 ppm level. Results showed good reproducibility for the fortified liver and muscle samples. Mean interlaboratory recoveries and percent coefficients of variation at about 4 ppm were 87.1 and 10.9%, respectively, for muscle and 87.4 and 7.5%, respectively, for liver. The interlaboratory analyses of the dosed liver and muscle tissues produced concentration levels similar to those obtained by the sponsor. The confirmatory procedure, which identified DNC in purified tissue extracts, used liquid chromatography-thermospray/mass spectrometry. The confirmatory procedure was successfully evaluated by one FDA laboratory. PMID- 8471869 TI - Calculation of juice content in a diluted fruit juice beverage. AB - A 1990 amendment to the Food, Drug and Cosmetic Act states that if a food purports to be a beverage containing vegetable or fruit juice, it shall be deemed to be misbranded unless its label bears a statement of the total percentage of such fruit or vegetable juice content. The intent of the present paper is to assist beverage manufacturers in calculating the juice content of their products for the purpose of a label declaration. PMID- 8471870 TI - Incidence of fungi in shared-use cosmetics available to the public. AB - A survey was conducted to assess both the potential health risk from shared-use cosmetics caused by microorganisms and the microbial efficacy of preservatives in cosmetics. Samples of 3027 shared-use cosmetic products were collected from 171 retail establishments nationwide. Fungi were present in 10.4% of the products, and 3.9% contained fungal pathogens or opportunistic pathogens. The 423 fungal isolates identified represented 33 genera and at least 69 species. A disproportionately large share of the fungal isolates were from eye products; fewer were from lip products. Pathogenic or opportunistic pathogens made up 32.2% of the fungal isolates. A slightly lower percentage of samples that contained preservatives had fungi, a fact suggesting that preservatives reduce the incidence of fungi in cosmetics. Results of this survey indicate potential microbiological problems concerning the safety of shared-use cosmetics. PMID- 8471871 TI - Animal drugs. PMID- 8471872 TI - Method. I. Liquid chromatographic determination of tiamulin hydrogen fumarate in feed premixes. PMID- 8471873 TI - Method. II. Liquid chromatographic determination of tiamulin hydrogen fumarate in tiamulin-poly(vinyl chloride) formulations. PMID- 8471874 TI - Method. III. Liquid chromatographic determination of tiamulin hydrogen fumarate in complete swine meal feeds. PMID- 8471875 TI - Method. IV. Gas chromatographic determination of tiamulin residues in swine liver. PMID- 8471876 TI - Method. V. Gas chromatographic/mass spectrometric confirmation of 8 hydroxymutilin, a tiamulin metabolite, in swine liver extracts. PMID- 8471877 TI - [Results of psychosomatic research and their use in gynecology]. AB - Several more recent research results in psychosomatic obstetrics and gynecology will be presented, and directions for the practice will be given. In conclusion, it will be discussed how, for the realization of psychosomatic concepts, 'old fashioned thinking' with biased, monocausal, scientific approaches is unproductive. This concerns, in particular, university gynecological hospitals where psychosomatic thinking is only very hesitantly accepted. The goal is, therefore, to promote a new thinking process, which incorporates an increased consideration of reference points like sensibility, flexibility and creativity. PMID- 8471878 TI - [Management of recurrent genital herpes virus infections in gynecology and obstetrics]. AB - Continuous oral therapy with acyclovir (200 mg four times a day or 400 mg twice daily) has been shown to be safe and effective in reducing recurrence of genital herpes by 74-93%. Continuing therapy appears to be safe, even when used for up to 4 years. When an episode of genital herpes is diagnosed in term pregnancy, cesarean section should be considered, even if intrauterine infection is possible until the rupture of membranes. The efficacy of suppressive therapy in term pregnancy to reduce the cesarean section rate is the objective of ongoing studies. PMID- 8471879 TI - [The reproductive medicine legislation: new legal responsibilities for the Austrian gynecologist]. AB - In spring 1992 the Austrian Parliament has enacted a new law dealing with reproductive medicine. The 'Act on medically assisted conception' contains provisions which totally prohibit particular methods of assisted fertilization (such as embryo or egg donation). The main goal of the act, however, is to regulate procreative medicine and to amend the Austrian General Civil Code: the parents-to-be are now considered to have the legal rights and responsibilities of biological parents in any case. PMID- 8471880 TI - [Changes in indications for obstetric peridural anesthesia in our clinic]. AB - In relation to the Swiss average our hospital has had a constant high rate of spontaneous deliveries and a low rate of cesarean sections. On the other hand the rate of obstetrical peridural anesthesia has been increasing significantly since 1986. This is above all related to its more frequent usage in cases of cervical dystocia and intolerable birth pain. Exactly in these indications peridural anesthesia has been very successful. In almost three quarters of the above mentioned cases a cesarean section can be avoided due to peridural anesthesia. PMID- 8471882 TI - [Ossification of the endometrium: an unusual finding in secondary sterility]. AB - The rare fact of endometrial ossification can be found after abortion or chronic inflammation. We describe a case from our clinic. Despite repeated curettages new ossifications occurred. The resulting secondary infertility is persisting. PMID- 8471881 TI - Intraperitoneal carboplatin in advanced ovarian carcinoma. AB - 24 patients with advanced epithelial ovarian cancer, who demonstrated a clinical complete or partial response to the induction of intravenous chemotherapy, underwent implantation of a subcutaneous semipermanent port-and-catheter system (Port-A-Cath) for intraperitoneal chemotherapy, which consisted of carboplatin 300 mg/m2 every 4 weeks. The median survival was 27.4 months for minimal residual disease versus 8 months for bulky disease (p = 0.0054). The median progression free interval was 15.7 months for minimal residual disease versus 1.8 months for bulky disease (p = 0.008). There were 3 complications (12.5%) related to the catheter: 1 perforation of the large bowel and 2 catheter inflow obstructions. Myelosuppression, especially a grade 3 leucopenia in 5 patients (25%) and a grade 4 thrombopenia in 3 patients (15%), was the dose-limiting toxicity. Even with maximum cytoreductive surgery and second-line intraperitoneal carboplatin-based chemotherapy, the 5-year progression-free survival (4.1%) remains very small. PMID- 8471883 TI - [Erroneous interpretations of archaeologic findings in ancient gynecology]. AB - The author reviews some archaeologic findings, interesting for medical history, in the field of gynaecology. Due to erroneous opinions, they were described a few years ago in an incorrect manner in wide-spread publications. PMID- 8471884 TI - [Recommendations for substitution with estrogens and progesterones in climacteric and in postmenopause. 8th Professional Meeting of the Zurich Discussion Group, November 1992]. PMID- 8471885 TI - [Good future perspectives and optimistic attitude. AIDS congress in Amsterdam]. PMID- 8471886 TI - [Anatomic principles of surgical therapy of stress incontinence]. PMID- 8471887 TI - [Results of incontinence operations: comparative study]. PMID- 8471888 TI - [Incontinence operations--the procedure at the Vienna 1st University Gynecologic Clinic]. PMID- 8471890 TI - [2d International Graz Symposium of diabetes in pregnancy]. PMID- 8471889 TI - [Abdominal, vaginal or combined: different approaches to a common goal?]. PMID- 8471891 TI - [Reports of the Austrian Society of Gynecology and Obstetrics]. PMID- 8471892 TI - Urinary tract infections. Management mayhem? PMID- 8471893 TI - Routine examinations the best approach. PMID- 8471894 TI - Guilt and sexually transmitted diseases. PMID- 8471895 TI - Tororo project. PMID- 8471896 TI - Radiology rounds. Angiomyolipoma. PMID- 8471897 TI - Dermacase. Candidiasis. PMID- 8471898 TI - Residency without walls. The University of British Columbia's Chilliwack program. PMID- 8471899 TI - Treating acute urinary tract infections. An RCT of 3-day versus 7-day norfloxacin. AB - A randomized, controlled trial was carried out to compare two courses of treatment in women with acute urinary tract infection in general practice. The 3 day course of treatment was found to be as effective as, and cheaper than, the 7 day therapy. PMID- 8471900 TI - Illicit drug use among adolescent students. A peer phenomenon? AB - Illicit drug use was studied in 2071 students 11 to 18 years of age. Almost all drug users had friends who consumed drugs, compared with only one third of those who did not use drugs. This suggests a bond between adolescent drug users, who form a distinct group of which most students are unaware. PMID- 8471901 TI - Continuity of care in the family medicine residency. Results of a national survey of program directors. AB - Based on the results of a survey of family medicine residency program directors across the country, there is a need for a national consensus on the definition of continuity of care, and on structures for teaching it and methods of evaluating it. PMID- 8471902 TI - Managing chronic pain in family practice. AB - Pain is common in family practice. In dealing with chronic pain, both the family physician and the patient often have problems in defining and in understanding the origin of chronic pain and in providing effective pain relief. This article explores a practical, holistic approach to understanding and managing chronic pain. PMID- 8471903 TI - Successful management of chronic pain syndrome. AB - Managing patients with chronic pain syndrome can be frustrating and unrewarding. Much of the difficulty experienced when managing these patients stems from an incomplete understanding of pain, especially the difference between acute and chronic pain. Pain theory and treatment of chronic pain syndrome are reviewed. An alternative management strategy for chronic pain syndrome is presented and the literature is reviewed. PMID- 8471904 TI - Managing pain in children. Changing treatment of headaches. AB - With growing understanding of the pain system and the variables that contribute to pain-suppressing mechanisms, treatments combining pharmacologic and psychologic methods are becoming the norm for managing pediatric pain. For headaches, however, the trend is away from medication and toward self-management strategies using relaxation, hypnosis, and lifestyle changes. PMID- 8471905 TI - Prenatal diagnosis of congenital anomalies. What can and should be done? AB - Prenatal diagnosis of congenital anomalies provides an opportunity to prepare and counsel parents. It can lead to pregnancy termination; to a change in timing, mode, or location of delivery; or, in some cases, to prenatal intervention. Families with an affected fetus are best managed by a cohesive medical team. This article outlines the principles used to manage these cases. PMID- 8471906 TI - Sexual medicine in family practice. Part 1: How to help. AB - Family physicians are in a unique position to help patients with sexual problems. They know their patients over a long time and often have both partners as patients. Most problems require minimal intervention, usually by providing information. Family physicians are sometimes the only professionals who are trusted enough to be told of abusive or incestuous situations. PMID- 8471907 TI - Sexual medicine in family practice. Part 2: Treating sexual dysfunction. AB - Sexual problems can be caused by organic or psychological factors, or a combination of the two. Deciding which leads to an appropriate management plan. This paper describes the current status of treatments for common sexual dysfunctions seen in family practice. PMID- 8471908 TI - Cycling injuries. AB - Bicycle-related injuries have increased as cycling has become more popular. Most injuries to recreational riders are associated with overuse or improper fit of the bicycle. Injuries to racers often result from high speeds, which predispose riders to muscle strains, collisions, and falls. Cyclists contact bicycles at the pedals, seat, and handlebars. Each is associated with particular cycling injuries. PMID- 8471909 TI - The diet game. Weighing the options. AB - As a major source of nutrition information for the public, physicians have a responsibility to assist their patients to make safe choices about weight loss programs. While most diet programs result in weight loss, the "quick fix" potentially is harmful. This article describes weight control options and their strengths and weaknesses. PMID- 8471910 TI - Gastric myiasis. Role of the lesser housefly. PMID- 8471911 TI - Family medicine research. PMID- 8471912 TI - Interventional genetics and cancer treatment. PMID- 8471913 TI - Fluoridation in Britain today. PMID- 8471914 TI - Urban slums and primary health care. PMID- 8471915 TI - All the homeless people--where do they all come from? PMID- 8471916 TI - Mainstream America hears it is safe from AIDS. PMID- 8471917 TI - Health inequalities: new concerns about the children of single mothers. AB - OBJECTIVES: To show that the exclusion from conventional class based analyses of child mortality of children whose parents are classified as "unoccupied" produces a misleading picture of health inequalities. DESIGN: Reanalysis of data published in the childhood supplement of the registrar general's decennial supplement on occupational mortality in England and Wales, which compares numerator data for registrations of deaths in children over the age of 1 but below their 16th birthday in 1979, 1980, 1982, and 1983 with data about children aged 1-15 who were enumerated at the 1981 census. RESULTS: Parents who are classified as "unoccupied" largely consist of economically inactive single mothers. Their children are estimated to represent 89% of the 614,000 aged 1-15 classified as "unoccupied" in the childhood supplement. They have the worst mortality record of all social groups--an age specific death rate of 68.8/100,000 a year, 42% worse than in social class V (48.4/100,000) and worse than that of social class I (22.8) by a factor of 3. At older ages (10-15 years) these children have a relative risk of death of 4.14 relative to classes I and II; the risk is 2.58 in children 0-4 and 2.56 in those 5-9. Relative risks of child mortality in social classes I and II in comparison to classes IV and V suggests a progressive shallowing from 2.08 at ages 1-4 to 1.37 at ages 10-15. When unoccupied parents were combined with classes IV and V and compared with classes I and II, however, inequalities seemed to be pervasive throughout childhood; the relative risks were 2.21 for those aged 1-4 and 1.98 for those aged 10-15. CONCLUSION: Children classified as unoccupied are almost certainly living in poverty as well as experiencing relatively high risks of mortality. Class based analyses which exclude them therefore produce a misleading picture of inequalities in child health. The implications for health policy are profound. Strategies to promote the nation's health should acknowledge the importance of material and social deprivation more explicitly. PMID- 8471918 TI - Epidemiology of Alzheimer's presenile dementia in Scotland, 1974-88. AB - OBJECTIVE: To describe the epidemiology of presenile Alzheimer's disease in Scotland from 1974 to 1988. DESIGN: Retrospective review of hospital records of patients aged less than 73 years admitted to psychiatric hospital with various diagnoses of dementia. Diagnoses were classified by National Institute for Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association Criteria and the Hachinski score. Completeness of the study sample was evaluated by scrutiny of neurology outpatient and general hospital records. SETTING: All general psychiatric hospitals in Scotland. SUBJECTS: All patients with onset of dementia aged 40-64. MAIN OUTCOME MEASURES: Probable and broad Alzheimer's disease, sex of patient, age at onset. RESULTS: 5874 psychiatric hospital records, 129 neurology outpatient records, and 89 records from non psychiatric hospitals were examined. 317 patients met criteria for probable Alzheimer's disease, 569 met criteria for broad Alzheimer's disease, and 267 met those for multi-infarct dementia. Minimal incidences per 100,000 population aged 40-64 years were 22.6 (95% confidence interval, 20.2 to 25.2) and 40.5 (38.9 to 42.3) per 100,000 for probable and broad Alzheimer's disease. In the 1981 census year the annual incidence of probable Alzheimer's disease was 1.6 (1.0 to 2.6). Women were at greater risk with incidence rates for probable Alzheimer's disease of 28.2 (24.5 to 32.4) per 100,000 compared with 16.5 (13.8 to 19.8) per 100,000 for men. The incidence per 100,000 for multi-infarct dementia was greater in men (25.1, 23.3 to 27.1) than women (13.4, 12.1 to 14.8). CONCLUSION: Female sex seems to be positively associated with development of Alzheimer's disease before age 65 years. PMID- 8471919 TI - Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability. AB - OBJECTIVE: To examine the evidence for using selective serotonin reuptake inhibitors instead of tricyclic antidepressants in the first line treatment of depression. DESIGN: Meta-analysis of 63 randomised controlled trials comparing the efficacy and acceptability of selective serotonin reuptake inhibitors with those of tricyclic and related antidepressants. MAIN OUTCOME MEASURES: Improvement in mean scores on Hamilton depression rating scale for 53 randomised controlled trials. Pooled drop out rates from the 58 trials which reported drop out by treatment group. RESULTS: Among the 20 studies reporting standard deviation for the Hamilton score no difference was found in efficacy between serotonin reuptake inhibitors and tricyclic and related antidepressants (standardised mean difference 0.004, 95% confidence interval -0.096 to 0.105). The difference remained insignificant when the remaining 33 studies that used the 17 item and 21 item Hamilton score were included by ascribing weighted standard deviations. The odds ratio for drop out rate in patients receiving serotonin reuptake inhibitors compared with those receiving tricyclic antidepressants was 0.95 (0.86 to 1.07). Similar proportions in both groups cited lack of efficacy as the reason for dropping out but slightly more patients in the tricyclic group cited side effects (18.8% v 15.4% in serotonin reuptake group). CONCLUSIONS: Routine use of selective serotonin reuptake inhibitors as the first line treatment of depressive illness may greatly increase cost with only questionable benefit. PMID- 8471920 TI - Dental disease and risk of coronary heart disease and mortality. AB - OBJECTIVE: To investigate a reported association between dental disease and risk of coronary heart disease. SETTING: National sample of American adults who participated in a health examination survey in the early 1970s. DESIGN: Prospective cohort study in which participants underwent a standard dental examination at baseline and were followed up to 1987. Proportional hazards analysis was used to estimate relative risks adjusted for several covariates. MAIN OUTCOME MEASURES: Incidence of mortality or admission to hospital because of coronary heart disease; total mortality. RESULTS: Among all 9760 subjects included in the analysis those with periodontitis had a 25% increased risk of coronary heart disease relative to those with minimal periodontal disease. Poor oral hygiene, determined by the extent of dental debris and calculus, was also associated with an increased incidence of coronary heart disease. In men younger than 50 years at baseline periodontal disease was a stronger risk factor for coronary heart disease; men with periodontitis had a relative risk of 1.72. Both periodontal disease and poor oral hygiene showed stronger associations with total mortality than with coronary heart disease. CONCLUSION: Dental disease is associated with an increased risk of coronary heart disease, particularly in young men. Whether this is a causal association is unclear. Dental health may be a more general indicator of personal hygiene and possibly health care practices. PMID- 8471921 TI - Racial discrimination against doctors from ethnic minorities. PMID- 8471922 TI - Communication between general practitioners and child psychiatrists. PMID- 8471923 TI - Drug misusers in Lothian: changes in injecting habits 1988-90. PMID- 8471924 TI - Heartsink hotel revisited. PMID- 8471925 TI - General practitioner fundholding: experience in Grampian. AB - Proposals for fundholding were greeted with scepticism by many general practitioners, and in Scotland the BMA persuaded the government to allow a scheme to test the arrangements as a demonstration project operating "shadow" practice funds. This allowed the six selected practices to set up administrative and computer systems without the worry of dealing with real money. The shadow fundholding scheme has since been extended to small practices and to a trial of fundholding for all services except accident and emergency. The six practices in the original pilot have all become fundholders and are beginning to effect improvements in the service to their patients. However, with more practices becoming fundholders negotiating contracts with providers is becoming increasingly complicated and more time and money needs to be put into this aspect. PMID- 8471926 TI - The fundholding debate: should practices reconsider the decision not to fundhold? PMID- 8471927 TI - NHS internal market 1991-2: towards a balance sheet. AB - The first year of the internal market in the NHS has been claimed to have resulted in increased efficiency. These claims, however, are hard to substantiate because the systems for operating the market are not fully in place. Examination of data on tax relief for private health insurance premiums for over 60s, general practice fundholding, and implementation and transaction costs suggest that much of the increased efficiency is not due to the reforms but to increased funding. Furthermore, some of the changes seem to be decreasing market forces and reducing efficiency. PMID- 8471928 TI - Letter to Mrs Bottomley. PMID- 8471929 TI - Cell to cell and cell to matrix adhesion. PMID- 8471930 TI - ABC of sleep disorders. Withdrawal from hypnotic drugs. PMID- 8471931 TI - Epilepsy mistaken for panic attacks in an adolescent girl. PMID- 8471932 TI - Hunting the gowk?--Psychiatric community care in Scotland. AB - The implementation of the community care changes throughout the United Kingdom from 1 April will mark the culmination of a series of major health and social care reforms. The avowed aims of achieving value for money and improved consumer choice through the introduction of competitive internal markets have yet to be tested. The political complexion of Scotland means that any proposed change to the NHS has tended to be greeted with a mixture of suspicion and resistance. As a result very few self governing trusts and fundholding general practices exist north of the border. And although Scotland has not had a wide reaching policy of moving psychiatric patients out of hospitals, community care for mentally ill people has advanced spontaneously. PMID- 8471933 TI - Improving London's health service. PMID- 8471934 TI - Improving London's health services. PMID- 8471935 TI - Priorities in first aid. PMID- 8471936 TI - Effect of NHS reforms on GPs' referral patterns. PMID- 8471937 TI - Effect of NHS reforms on GPs' referral patterns. PMID- 8471938 TI - Authors have rights too. PMID- 8471939 TI - Authors have rights too. PMID- 8471940 TI - Authors have rights too. PMID- 8471941 TI - Authors have rights too. PMID- 8471942 TI - Liver failure induced by paracetamol. PMID- 8471943 TI - Organ donation after paracetamol overdose. PMID- 8471944 TI - Obstetric outcome should be analysed by parity. PMID- 8471945 TI - Diagnostic dilatation and curettage. PMID- 8471946 TI - Diagnostic dilatation and curettage. PMID- 8471947 TI - Hypoglycaemia with human and porcine insulins. PMID- 8471948 TI - Hypoglycaemia with human and porcine insulins. PMID- 8471950 TI - Prescribing folic acid. PMID- 8471949 TI - Prevalence of toxoplasma IgG. PMID- 8471951 TI - FHSAs and prescribing. PMID- 8471952 TI - General practitioners' views of their FHSA. PMID- 8471953 TI - GPs in partnership with management. PMID- 8471954 TI - Drugs, secrecy, and society. PMID- 8471955 TI - Drugs, secrecy and society. PMID- 8471956 TI - Effects of treatment with Pluronic F-68 during continuous venous air embolism in swine. AB - Treatment with the surface-active agent Pluronic F-68, shown to modulate the hemodynamic effects of venous air emboli (VAE) in dogs, may be useful for treatment of VAE in divers. We report on the effects of injections of Pluronic F 68 on responses to continuous air infusion in swine. Pretreatment made no significant difference in any hemodynamic or ventilatory variables, but the rise of pulmonary vascular resistance caused by air infusion was greater in surfactant treated animals; this was also evident after a second treatment during the air infusion. The small effect of surfactant treatment in our study on swine contrasts the effects reported previously in dogs, and could be due to species specific differences in lung physiology-anatomy, or due to difference in experimental design. We speculate that the minor changes we observed were caused by deeper penetration of the bubbles into the pulmonary arterial tree after surfactant treatment. PMID- 8471957 TI - Alveolar gas exchange during simulated breath-hold diving to 20 m. AB - Alveolar gas exchange, as affected by changes in pulmonary blood flow, was studied in five subjects performing breath holds lasting 75 s at the surface and during compression to 20 m in a hyperbaric chamber. After reaching the maximal depth, VO2 started to increase, compared to control, reaching a maximum of 346 +/ 66 (SE) ml (STPD).min-1.m2 (body surface area) at 50 s, i.e., early in the ascent; it exceeded the 50-s surface breath-hold value by 214 +/- 9 ml.min-1.m2. During descent, CO2 was absorbed from the alveoli into the blood, initially at 140 +/- 24 ml.min-1.m2; during ascent CO2 was transferred back into the lungs. These changes reflected compression and expansion of lung air. The increase in VO2 during the dives, which are not steady states, may be explained by an increasing cardiac output at depth. An augmented cardiac output had earlier been observed under identical conditions and explained by a drop in transthoracic pressure, enhancing venous return. Upon surfacing, the PAO2 was about 20 mmHg lower than after surface breath holds, reflecting the effects of changes in cardiac output. PMID- 8471958 TI - Spinal decompression sickness: hydrophobic protein and lamellar bodies in spinal tissue. AB - Four basic studies have addressed the question of why the spinal cord is so vulnerable to decompression injury, with symptoms exceeding those related to the brain by a ratio often quoted as 3:1. Hydrophobic protein (HP) was discovered in sheep spinal tissue at roughly 3 times (3.3:1) the level in brain and several orders of magnitude greater than in skeletal muscle or plasma. Extravascular lamellar bodies (LBs) of largely phospholipid (PL) were also demonstrated in spinal tissue by electron microscopy using a special fixative, the population being 4.1 times that in brain tissue where some LBs were found adjacent to vascular endothelium. Extracts of spinal surfactant (HP+PL) were found to be particularly surface active on the Langmuir trough, with the HP greatly accelerating monolayer equilibration, especially the recruitment of PL to a rapidly expanding air-aqueous interface. The PL/HP surfactant complex was found to render surfaces hydrophobic when they were able to initiate "strings" of bubbles in supersaturated solutions of gases. These results are discussed as favoring the concept of autochthonous bubbles causing spinal decompression injury exacerbated by the large quantities of spinal surfactant present. PMID- 8471959 TI - Effect of hyperbaric and normobaric oxygen on pulmonary endothelial cell function. AB - The effect of prior exposure to raised partial pressures of oxygen on pulmonary endothelial cell function was assessed in the isolated perfused rat lung preparation. Prolonged exposure to both 1 bar (48 h) and 2.5 bar (11 h) of oxygen caused pulmonary edema and dyspnea. Exposure to 1 bar oxygen for 48 h (approximately 0.66 lethal duration) caused a decrease in pulmonary 5 hydroxytryptamine (5-HT) clearance, suggesting compromised endothelial cell integrity. No change in 5-hydroxy-indole acetic acid (5-HIAA) efflux was noted. However, exposure to 2.5 bar of oxygen for up to 11 h (approximately 0.85 lethal duration) did not decrease pulmonary 5-HT clearance, implying that endothelial cell integrity was not compromised after this oxygen exposure. Exposure to 2.5 bar oxygen resulted in a reduction in 5-HIAA efflux, possibly indicating a decrease in metabolism of cleared 5-HT. The absence of a demonstrable impairment of 5-HT clearance during the development of pulmonary toxicity on exposure to 2.5 bar of oxygen suggests that there may be important differences in pathologic mechanisms in response to oxygen exposure at partial pressures 1 and 2.5 bar. PMID- 8471960 TI - Relationship between the event-related brain potential P300 and inert gas narcosis. AB - It is known that inert gas narcosis slows both reaction time (RT) and the event related brain potential P300 in a correlated and dose-dependent manner. On the assumption that P300 reflects the time to evaluate a stimulus and RT reflects this time plus the time to select and execute a response, these results have been taken to indicate that the locus of the slowing produced by narcosis is early and influences stimulus evaluation processes. If this is the case, RT and P300 should be slowed identically when cognitive workload is manipulated. To test this prediction, subjects breathed 35% nitrous oxide and responded to differences in the intensity of either visual (Exp. 1, n = 8) or auditory (Exp. 2, n = 10) two choice oddball stimuli with accuracy controlled at a high level. In both experiments narcosis slowed RT and P300 additively by increasing the intercept rather than the slope of the workload function, but these two measures diverged in one important respect; RT was slowed more than P300, as indicated by an RT P300 difference analysis. It is concluded that, contrary to previous assumptions, narcosis produces two sources of slowing; one stimulus-related and indexed by P300 and the other response-related and indexed by the RT-P300 difference. Possible mechanisms underlying these sources are discussed. PMID- 8471961 TI - Computer simulation of counterlungs. AB - We have developed a computer model of chest-mounted counterlungs, which accounts for counterlung shape, effective volume, and pressure centroid. The model has been validated and the principles are applicable to other counterlung systems. The highly non-linear and discontinuous behavior of a counterlung is predicted by use of a sophisticated numerical integration method that computes variables such as pressure and volume in the time domain. Three separate stiffness (reciprocal of compliance) terms have been used which contribute to the diver's work of breathing: material elastic stiffness, "gas" stiffness, and "hydrostatic" stiffness. The model provides a significant advance in the understanding of counterlung behavior, allowing the performance of practical equipment to be predicted. PMID- 8471962 TI - Changes in frequency of R-plasmid transport in high pressure. PMID- 8471963 TI - [The chromosomal sensitivity of hematopoietic cells in Xenopus laevis larvae to the action of the chemical mutagen fotrin]. AB - Using the method of counting micronuclei it was shown that, in peripheral blood of larva of frog exposed to high doses of alkylating agent fotrin, the abundance of erythrocytes with signs of chromosomal aberrations significantly exceeds the level of spontaneous mutations on the 16th, 24th and 30th days of fixation but not on the 7th day following the experiment onset. In addition, with all terms of fixation under examination, an increased in comparison with norm number of binuclear erythrocytes was observed in the population of erythroid cells. Our observations combined with the data obtained by other authors confirm that amphibian hemopoietic cells can be used as a reliable test system for the detection of cyto- and genotoxic compounds as well as for the genetic monitoring of water environment. PMID- 8471964 TI - [Microbial saprotrophic pharmacotherapy: the possible indications, the conditions for its realization and the overall strategy]. AB - Potential indications for bacterial strains-producers of biologically active substances to be utilized for microbial saprotrophic pharmacotherapy are presented. These indications include some infectious diseases and tumors, a number of noninfectious diseases, transplantation and contraception. The cardinal problem of microbial pharmacotherapy, the capacity of strains-producers of getting acclimatized to the patient organism, is discussed. For its solution, a "microbiological passportization of a patient" ("saprotrophic mapping"), that is drawing up a map of patient microbiological status, is proposed. This "saprotrophic secretory passportization (mapping)" of strains-producers is first submitted for consideration. A strategy of future microbial pharmacotherapy is stated. The necessity of careful approbation of this kind of therapy is emphasized. PMID- 8471965 TI - [The modelling of survival and mortality curves for human populations based on the theory of reliability]. AB - The reliability theory model of aging (Kol'tover 1981, 1982) was used for analysis of life-tables of Swedish males and females for 1951-1955, 1962-1973 and 1971-1975 calendar years. In terms of the model it has been possible 1) to explain the Gompertz "law" of mortality; 2) to describe quantitatively statistical life-table data including Gompertz's and geriatric ages; 3) to predict the behavior of mortality rate function depending on the extent of population heterogeneity, among them the existence, at respective degrees of heterogeneity, of a maximum in geriatric age range and 4) to estimate the species specific maximum life-span potential of animals. PMID- 8471966 TI - [The effect of the drug-induced activation and deprivation of the sympathetic nervous system on aldosterone receptor binding by the kidney with disturbed neurotrophic support]. AB - The results of studies are presented on the determination of aldosterone accumulation by mineralocorticoid receptors on cytoplasm and nuclei of normal rat renal tubules as well as in disturbed neurotrophic supply of the kidney including that against the background of activation and deprivation of the sympathetic nervous system function. It was shown that a pharmacological stimulation of sympathetic nervous system potentiated functional disturbances of the renal mineralocorticoid receptor apparatus in reflex dystrophy of the kidney. A simultaneous pharmacological blockade both of neural and of humoral transmission of pathological stimuli from damaged sciatic nerve to the kidney prevented the development of these disturbances. A belief is stated that there is a possibility of using adrenoceptor blockers as means to prevent or inhibit the development of dystrophic alterations in the organism which appear under the lesion of one or other part of the nervous system. PMID- 8471967 TI - [The effect of cytostatic and immunomodulator therapy on the morphology of the tumor and lymphoid organs and on the count of large granular lymphocytes in the blood of mice with Lewis carcinoma]. AB - Effects of separate and combined therapy with nitrosomethylurea (NMU), methotrexate thymalin, and reaferon on tumor, thymus and spleen morphology as well as the content of large granular lymphocytes in blood were studied in mice with Lewis lung carcinoma. The study revealed different effects of methotrexate and NMU on tumor and lymphoid organs. The direct NMU damage to tumor was accompanied by a suppression of host immune system which was only slightly reversed with immunomodulators. The cytotoxic antitumor effect of methotrexate was probably related also with the stimulation of host immune system, its cells in turn affecting the size of proliferating tumor fraction. PMID- 8471968 TI - [Changes in the structure of the respiratory chain of the mitochondria from different tissues in relation to the conditions of mammalian development]. AB - The content and stoichiometric relations of respiratory chain cytochromes were studied in mitochondria from femoral muscles of Wistar rats developing either under the conditions of hypokinesia or in near-natural ones. It was shown that, during early postnatal ontogenesis (until puberty), the maximum level of cytochrome aa3 was achieved already within the playing period (by the 30th day) in animals developing under near-natural conditions while in the group with locomotory deprivation, it was approached only in the midst of puberty (by the 45th day). By the age of sexual maturity (the 60th day), the oxidative potential was higher in the group with natural development. Stoichiometric changes occurred in the relation of muscular cytochromes within the considered period. The cytochrome b562/aa3 ratio in 30-day-old rat pups from the group with "normal" development was twice as high as in adults. Similar alteration of this ratio was observed also in the group of animals developing under the conditions of hypokinesia though 5 days later. The interorganic analysis showed that the cytochrome ratio similar to that observed in muscles of rat pups within the playing period was characteristic of the liver and similar to that of adults-of the brain. Functional peculiarities of mitochondrial activity was studied on mitochondria isolated from brain and liver of adult animals. It was shown that the difference in respiratory chain structure, mainly in the b562/aa3 ratio, was connected with different substrate specificity. Brain mitochondria characterized with the b562/aa3 ratio below 1 possessed a higher affinity to NADH-dependent substrates while hepatic mitochondria with the ratio above 1-to FADH-dependent substrates. PMID- 8471969 TI - [The rate of development, temperature and genetic control]. AB - The rate of poikilothermic animal development may be expressed quantitatively only with a specification of temperature at which this development occurs and on which this value depends. Therefore the species feature is not the rate of development itself but the character of its dependence upon the temperature and the range of temperature within which this development is possible. Obviously, the character of this dependence may be in principle expressed by an equation which functional form and parameters are inherited like all other features of the species. Therefore there should exist genes determining these parameters. Thus there is a one-to-one correspondence between the organism genetic apparatus, the rate of development and the temperature. The given article presents some theoretical and experimental approaches to the study of mechanisms of this correspondence. PMID- 8471970 TI - [The characteristics of the expression of temperature-dependent dominant lethal mutations in Drosophila melanogaster]. AB - The results of a series of investigations on obtaining and analysing dominant temperature-sensitive lethals (DTS-lethals) are summarized. Using EMS, both cold- and heat sensitive mutations of this type were induced in large autosomes. The cold-sensitive mutations of chromosome 3 were revealed for the first time. The effect of genetic phone on DTS lethal penetrance and expressivity was studied. The character of expression of two mutations possessing a pleiotropic action was examined. The heat-sensitive 1(2)M90DTS mutation disturbed the structure of abdominal tergites in all imago and, besides, caused an abrupt decrease in the female reproductive period. The pattern of alterations observed in oogenesis along with the result of phenogenetic analysis suggest that this gene takes part in the genetic control over the proliferation of stem oogonial cells. The cold sensitive 1(2)M66DCS mutation caused a number of disturbances in imago thoracic structures: inability to flight, raised up wings, extremity fracture, etc. Mutant flies showed serious disorders of indirect flight muscles both at morphological and at ultrastructural levels. It was established that this mutation was a cold sensitive allele of Mhc gene which controls the synthesis of myosine heavy chains in drosophila. PMID- 8471971 TI - [The prospects for the development and use in ecological research of a cytogenetic method of analysing micronuclei in hepatocytes]. AB - The article deals with peculiarities of hepatocyte proliferation which determine the fields of uses for a micronuclear test in hepatocytes and first of all for ecological biomonitoring of genotoxic pollution. Theoretical problems are considered that substantiate applied practices for performing the micronuclear test. Among them there are methods of stimulating the mitotic activity (partial resection of liver, necrogenic hepatotoxins, chemical inductors of adaptive growth); effects of cellular kinetics (volume of proliferative pool, blockade of premitotic period) on quantitative criteria of the method. The capacity of hepatocyte population to preserve and accumulate injuries of genetic material is discussed. PMID- 8471972 TI - [The cytogenetic monitoring of the southern Aral Sea area. An evaluation of the genotoxic activity of the water]. AB - The work gives the data indicating the ability of water sampled from different sources of South Priaralje to induce chromosomal abnormalities in somatic and sexual cells of mammals. It has been shown also that the studied water samples can exert modifying effects on the clastogenic activity of supermutagen nitrosomethylurea. Season-dependent fluctuations of level of spontaneous and induced mutations have been revealed in three tissue systems (liver, cerebellum, and spermatogenic epithelium). PMID- 8471973 TI - [The cytostructure and cytochemistry of the retinal pigment epithelium]. PMID- 8471974 TI - [The use of preparations of protozoan origin as agents for the prevention and early therapy of combined radiation-thermal injuries]. AB - Radioprotective and therapeutic effects of astazian and astazilide, the drugs of protozoan origin, were studied in comparison with known modifiers of biological reactions (bacterial polysaccharides, synthetic polypeptides) in combined radiation-thermal injuries (CRTI). The efficiency of drugs under examination was found to be time- and dose-dependent. Application of the drugs of protozoan nature 24 hours prior to or 1 hour following CRTI provided 30 to 50% survival of experimental animals for 30 days as compared to 4.5% in the group of untreated mice. Administration of the drugs 3-7 days following CRTI exerted no therapeutic effect. PMID- 8471975 TI - [Krezatsin--a stimulant of the activity of regenerating liver cells]. AB - In experiments with partial hepatectomy in rats, the application of cresacin was shown to potentiate processes of hepatocyte regeneration, to increase high-energy compounds therein, and to accelerate some phases of mitotic cycle. These processes occur along with an inhibition of lipid peroxidation in hepatocytes, a decrease in the rate of transmembrane oxygen transport in mitochondria, and a reduction of cytochrome oxidase amount. It was concluded that cresacin directly stimulates diverse links of metabolic pathway. PMID- 8471976 TI - [Changes in the intensity of free-radical reactions in the organs of rats under hypokinetic stress and with protection by the delta sleep-inducing peptide and its tyrosine-containing analog]. AB - Dynamics of the hypokinesia-induced changes of free radical and malonic dialdehyde content in brain, the changes of respiratory chain state and superoxide dismutase activity in liver of rats has been studied using ESR technique and biochemical methods. The effect of the preliminary injection of DSIP and its analogue ID-2 on these dynamics has also been studied. Using a model system constants of the interaction between DSIP or ID-2 and O2-. have been determined. The data point to the antioxidant effect of the administration of the peptides before hypokinesia. This suggests that the effect involves in mechanisms of the anti-stress action of these peptides. PMID- 8471977 TI - Active immunization of children with leukemia and other malignancies. AB - Active immunization against measles, Haemophilus influenza B, tetanus, diphtheria, hepatitis B, influenza, poliomyelitis, and, when indicated varicella and pneumococcus induces long-lasting immunologic protection in most healthy pediatric vaccine recipients. Among children receiving immunosuppressive therapy for cancer, possible early loss of specific immunity acquired from prior vaccination or disease, and likely diminished responsiveness to initial or booster vaccination must be considered. In addition, the safety of vaccine administration requires separate study in this population. Published evidence demonstrates preservation of vaccine-induced antibody titers against tetanus, diphtheria, poliomyelitis and (in children treated for lymphoma) pneumococcus. In contrast, prior immunity to varicella, influenza, and hepatitis B (when naturally acquired), and measles (acquired by vaccination) is compromised during and/or after antineoplastic therapy. Studies of immunologic protection acquired by prior vaccination against hepatitis B, varicella, and H influenza have not been published. The safety of administering toxoids and inactivated vaccines in this population is well documented. In contrast, morbidity must be expected if live attenuated vaccines (oral polio vaccine, attenuated measles vaccine or attenuated varicella vaccine) are administered to children receiving anti-cancer therapy. The risks of using live vaccines should be measured against demonstrable benefits in any vaccine program. The response to initial or booster immunizations against tetanus and diphtheria are similar to those in healthy children. For all other immunizations reviewed, responsiveness is diminished during periods of chemotherapy, more strikingly in children treated for leukemia than for solid tumors. Antibody responses to these vaccines range from slightly blunted (in the case of H influenza B) to marginal (influenza) or completely useless (pneumococcus and hepatitis B in children treated for leukemia). PMID- 8471978 TI - Empiric treatment of localized infections in the febrile neutropenic patient with monotherapy. AB - Empiric therapy is necessary for febrile, neutropenic patients in order to minimise morbidity and mortality. Certain agents are now available for monotherapy which offer comparable success to combinations of either an aminoglycoside with a beta-lactam or two beta-lactams. However, no regimen offers complete treatment under all circumstances in all patients. It is also apparent that febrile, neutropenic patients comprise a more heterogeneous group than just those with bacteraemia, clinically apparent infection and unexplained fever. Localized infections occur in just under a third of cases at the onset of fever and a similar number will develop during the course of fever. Mortality is higher in infections that are accompanied by bacteraemia and also those that develop subsequently, especially when related to the lung. The aetiological agent also differs with each type of infection as does the duration of fever and symptoms. Consequently modifications are required more often. The length of treatment may also differ. Therefore, during the first 3-4 days of empiric therapy, every effort should be made to identify incipient localized infections in addition to detecting bacteraemia. Changes in therapy can then be based on objective grounds rather than continued fever offering more patients individual treatment than is possible when relying only on the temperature chart. PMID- 8471979 TI - Induction therapy for acute myelogenous leukemia in patients over 60 years with intermediate-dose cytosine arabinoside, mitoxantrone and etoposide. AB - Twenty-three patients greater than age 60 years with acute myelogenous leukemia (AML) received induction therapy with continuous infusion cytosine arabinoside (1.5 g/m2/day, day 1-3), mitoxantrone (10 mg/m2/day, day 1-3) and etoposide (800 mg/m2, day 4). Patients entering complete remission (CR) were eligible to receive an identical consolidation cycle. Eighteen of the 23 patients (78%; 95% confidence interval 56% to 93%) entered CR. Twelve of these received consolidation therapy and 4 of these remain in remission at 3 to 20 months. Hematologic toxicity of the regimen was acceptable; only 1 patient died following therapy (having attained a CR). Non-hematologic toxicity was mostly mild (grade 2 or less) with one episode of grade 3 cerebellar toxicity. While this regimen induces a high CR rate in patients > age 60 years, relapses remain common and overall survival is too early to assess. PMID- 8471980 TI - Bisantrene in relapsed and refractory acute myelogenous leukemia. AB - Because of the lack of standard treatment in refractory and relapsed acute myelogenous leukemia (AML) several new drugs have been employed alone to evaluate their efficacy in this peculiar category of patient. Bisantrene, a new anthracene bishydrazone derivative, has shown antileukemic effect in phase I and II clinical trials with acceptable extrahaematological toxicity. Seven patients (six males and one female, median age 41.8 years) received Bisantrene (250 mg/sqm/daily 1-7) as a single agent in relapsed or refractory leukemia. 5 out of 7 patients achieved complete remission, one attained partial remission and one was resistant. However, haematological toxicity was severe with prolonged myelosuppression. Hepatic toxicity was the main extrahaematological side effect and occurred in 3 of 7 patients, however all of them recovered within 40 days. No cardiovascular dysfunction occurred although all the patients had been heavily previously treated with anthracyclines. Our data confirm that Bisantrere is active in relapsed and refractory AML and suggest the need for larger clinical trials to better evaluate its efficacy. PMID- 8471981 TI - Immunophenotype of acute lymphoblastic leukemia cells: the experience of the Italian Cooperative Group (Gimema). AB - The immunophenotype of 304 adult lymphoblastic leukemias (> 18 years) diagnosed on the basis of the FAB criteria was determined at the time of diagnosis using a panel of monoclonal antibodies. The series comprised cases diagnosed and immunophenotyped in 43 Italian centers (GIMEMA Cooperative Group) between April 1988 and June 1991. The immunophenotypic characterization consisted of two consecutive steps. The initial screening was based on the reactivity for TdT, HLA Dr, CD7, CD10, CD13, CD19, CD24, CD33 and CD41. According to the results obtained, the second level of investigation assessed the positivity for intra cytoplasmic (Cy) Ig, CD1a, CD2, CD3, CD4, CD5, CD8 and CD20. Based on the hierarchical expression of the different B- and T-cell related antigens, each case was assigned to a given differentiation stage. B-lineage ALL were classified in five subgroups (B0-B4) and T-lineage ALL in four subgroups (T0-T3). Cases in which the blasts were lymphoid according to the FAB criteria, but expressed myeloid antigens in association with B- and T-lymphoid markers were defined as hybrid leukemias. As expected, CD10+ cases (B2-B3) were the most frequent within the B-lineage ALL (83.2% of cases). CyIg+ (B3) accounted for about 20% of CD10+ ALL. Twenty eight cases (13.4%) were at a pre-cALL stage (B0-B1) and of these, 8 (3.8% of the total series) were positive only for TdT and HLA-Dr (B0). Intermediate and mature thymic phenotypes (T2-T3) were predominant within the T ALL (67.2%) groups. Five cases, were positive only for TdT and CD7 (CD5+), and classified as T0. 9.2% of cases fulfilled the definition of hybrid leukemia, largely in view of the co-expression of B-lymphoid and myeloid markers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8471982 TI - DNA image analysis in childhood acute lymphoblastic leukemia. AB - DNA index (DI) and percentages of cells in S and G2/M phase were determined in Feulgen stained nuclei of blasts from 31 cases of childhood ALL at diagnosis. In 6 cases the results of DNA analysis and cytogenetics were concordant showing hyperdiploidy. Two other cases with normal karyotype were revealed as DNA aneuploid with image analysis. Cases with cytogenetic abnormalities like translocation, deletion or presence of single or double supernumerary chromosomes had DI within normal ranges. Nine ALL cases (29%) were found to be DNA aneuploid- 8 hyperdiploid and 1 hypodiploid. The percentages of cells in S and G2/M phase for blasts from bone marrow (mean 17.6%) were significantly higher than those estimated in the peripheral blood (mean 1.57%). We conclude that analysis by image cytometry can detect aneuploid DNA content even in cases, which showed a normal karyotype and provides new information concerning the biological aspects of leukemic blasts. PMID- 8471983 TI - The surgical choice in neutropenic patients with hematological disorders and acute abdominal complications. AB - The clinical course of patients with hematological disease, especially after treatment, is often complicated by gastrointestinal infections. Between 1986 and 1990 a total of 18 patients affected with hematologic disease and presenting with an acute abdomen were admitted to the surgery department at the University of Rome "La Sapienza". Most patients were affected with acute or chronic myeloid leukemia (61%) and lymphoma. Five patients with acute appendicitis, three with necrotizing enterocolitis, three with spontaneous hemoperitoneum, three with cholecystitis, two splenic infarctions and two intestinal occlusions were diagnosed. Symptoms were often vague and non specific and blood counts revealed neutropenia in all but two patients, while anemia was characteristic in spontaneous hemoperitoneum and in neutropenic enterocolitis. Fungemia occurred in only two cases while bacteremia was present in seven. The most critical patients were those affected by neutropenic enterocolitis and acute cholecystitis. Sonography was meaningful in the diagnosis of hemoperitoneum, splenic infarct and acute cholecystitis. All patients underwent surgical procedures within 48 hours of admission to the department. In all cases peritoneal washing was performed and at least one peritoneal drainage was left. In all cases of necrotizing enterocolitis, intestinal resections, either ileal or colonic, were followed by an immediate anastomosis in two layers. Intensive hematological and antibiotic post surgical care was performed in all patients. Seven patients presented minor complications (38.8%), and only one died (5.5%). Emergency surgical treatment may be safely carried out in patients with hematological diseases presenting with an acute abdomen. Intensive postsurgical care is mandatory for the recovery of patients and the patient's critical condition should not be a deterrent to surgical intervention. PMID- 8471984 TI - A randomised trial of cyclophosphamide with and without low dose alpha-interferon in the treatment of newly diagnosed myeloma. AB - The role of alpha-interferon (IFN) in initial treatment of multiple myeloma is controversial. We have conducted a trial of cyclophosphamide with and without low dose IFN in newly diagnosed myeloma. Thirty four patients, mean age 63 were all given cyclophosphamide 600mg/m2 IV every 21 days while 17 were randomised to also receive IFN at a dose equivalent to 6mU per week. In the IFN group 8/15 assessable patients (53%) had a greater than 50% reduction in paraprotein compared with 4/16 (25%) of controls (p < 0.05). However the median duration of response was the same in the two groups (IFN 8 months, controls 8.5 months). After a median follow up of 28 months there is no significant difference in survival. Toxicity including myelosuppression was commoner in the IFN group. These findings suggest that the addition of IFN to cyclophosphamide is not likely to offer major benefits in treating myeloma. PMID- 8471985 TI - Resistance to lipophilic cationic compounds in multidrug resistant leukemia cells. AB - Previously we have shown that multidrug resistant cells are cross-resistant to certain permanently charged cationic lipophilic compounds. In the present study we extend these observations to additional cationic lipophilic compounds with unrelated chemical structures. Study of the growth inhibitory activity of series of triphenylalkyl-phosphonium and alkyl-ammonium compounds revealed that cross resistance to these compounds in multidrug resistant P-388 murine leukemia cells, was related to the presence of cationic charge but not to the molecular size/degree of lipophilicity. PMID- 8471986 TI - Primary pleomorphic T-cell lymphoma of the spleen. AB - We report a case of primary splenic T-cell lymphoma that posed difficult problems in differential diagnosis with erythrophagocytic T-gamma lymphoma and inflammatory pseudotumor of the spleen. The need for immunophenotypic and molecular studies for establishing the correct diagnosis and the importance of early detection and treatment, is emphasized in the light of the relatively good prognosis of splenic lymphoma, diagnosed in the early stages of disease. PMID- 8471987 TI - Sudden onset deafness as a presenting manifestation of chronic lymphocytic leukemia. AB - An unusual patient with typical Rai Stage 2 (Binet Stage A) chronic lymphocytic leukaemia (CLL), who presented with sudden onset deafness as the initial manifestation of disease is reported. This sensorineural hearing loss improved dramatically after the administration of chemotherapy. This unique observation was also associated with reduction of the circulating B-CLL cells and with the achievement of a partial response, lasting for almost three years. Recently there was another episode of sudden deafness, associated with a rising leukocyte count, and disease activity followed once again by recovery after chemotherapy. Audiograms were recorded showing positive findings on presentation and recovery after therapy. This very rare manifestation of CLL was presumed to be due to infiltration of the cochlear duct or the 8th cranial nerve although all imaging techniques were negative, because of the rapid relief and recovery achieved after specific chemotherapy. The importance of early diagnosis and therapy is stressed in the light of the rapid clinical recovery observed here. PMID- 8471988 TI - [Biosynthesis of human recombinant interleukin-8 in Escherichia coli]. PMID- 8471989 TI - [Monoclonal antibody ICO-92 against the transferrin receptor (antigen CD71)]. PMID- 8471990 TI - Effects of recovery duration and blood lactate level on power output during cycling. AB - This study identifies the quickest recovery between consecutive anaerobic tests to maintain power output (PO) on the repeated test. Sixteen male cyclists finished three sessions of max rpm initial and repeated 45-s cycling tests at 53.9 N. Tests were separated by 6, 9, or 12 min of recovery cycling (80 rpm, 9.8 N). Results showed no significant differences in PO between initial tests (M = 578.5 +/- 50 watts). PO was significantly less on the 6-min repeated test (M = 551.2 +/- 51) compared to the 9- (M = 575.1 +/- 53) and 12-min tests (M = 581.7 +/- 49.9) (p > 0.05). Net blood lactate [HLa] (repeated test-recovery) was significantly related to net PO (repeated test-initial test) on the 9- (r = 0.60, p < 0.05) and 12-min (r = 0.64, p < 0.001) trials, but not on the 6-min trial (r = 0.35, p = 0.19). In summary, at least 9 min of recovery cycling maintains PO on a repeated 45-s cycling test. Elevated [HLa] at the onset of high-intensity sprint exercise is moderately associated with PO on repeated cycle ergometer tests. PMID- 8471991 TI - Ageing and human muscle: observations from Sweden. AB - The purposes of this review are to summarize studies of cross-sections of autopsied whole muscles from previously physically healthy males and to focus on the cause of the ageing atrophy. The ageing atrophy begins around 25 years of age and thereafter accelerates. This is caused mainly by a loss of muscle fibres, and to a lesser extent by a reduction in fibre size, mostly of the proportion of the fibre area in the muscle cross-section occupied by type 2 (fast-twitch) fibres. In muscle from old subjects, there is a significant increase in the number of enclosed fibres, indicating an increased incidence of fibre type grouping, a loss of motor neurons in the spinal cord, and a reduction in the number of functioning motor units. These findings strongly suggest a combination of a progressive denervation process and an altered physical activity level as the two major mechanisms underlying the effects of normal ageing on human muscle. These changes have obvious implications for old individuals and their participation in physical activity and in sports, which must be accommodated in rehabilitation regimes or in training programmes. PMID- 8471992 TI - The effects of active and passive recovery on short-term, high intensity power output. AB - The advantage of active over passive recovery from long and intermediate duration exercise is well documented. Success has been attributed to metabolite washout and/or lactate (La) utilization by the active musculature. This study was designed to determine whether active recovery was superior to passive rest during short duration, high intensity performance. On 4 separate days, six athletes performed a set of eight 6-s power tests separated by 30-s recovery intervals under two recovery conditions. Recovery conditions involved either sitting passively on the bike (P) or actively pedaling (A) at 60 rpm using 1 kg resistance. A MANOVA on peak power (PP), fatigue rate (F), and total work (TW) showed a significant difference due to recovery condition, F(3, 169); p < .0001. Separate ANOVAs revealed that PP (A = 1192.85 watts, P = 1134.57 watts; p < .0001) and TW (A = 6.59 kJ, P = 6.23 kJ; p < .0001) differed significantly between conditions. No difference was found for F (A = 80.12 watts.sec-1, P = 79.80 watts.sec-1). Results indicate that active recovery provides superior performance to passive rest in repeated short-term, high intensity power activities. PMID- 8471993 TI - Stability of parameter estimates derived from the power/time relationship. AB - The hyperbolic relationship between power output (P) and time to exhaustion (t) is described as t = W'/(P-theta PA). The purpose of this study was to determine the stability of estimations of estimates of theta PA and W', said to reflect maximal sustainable power and anaerobic capacity, respectively. Thirteen women and 13 men performed five bouts of cycling exercise to exhaustion. Individual theta PA and W' were calculated from the results of these five bouts (Trial 1). These procedures were repeated (Trial 2). For both sexes, Trial 2 estimates of theta PA were 5 to 6% higher than Trial 1 estimates, but they were highly correlated. Mean W' estimates were the same in Trials 1 and 2, with higher trial to-trial correlations in the men than in the women. PMID- 8471994 TI - The relationship between cognitive characteristics and decision making. AB - Team handball players (N = 118) underwent a number of cognitive tests to examine how much of their decision making (DM) ability, as measured through responses to game slides projected to them for 2 seconds under low and high exertion levels (i.e., walking and running), was accounted for by cognitive components. A stepwise multiple linear regression indicated that experience was the most pronounced predictor of DM capacity in both exertion conditions. In the walking condition, concentrational consistency, avoidance of concentrational mistakes, and short-term memory, together with experience, produced a multiple R of 0.48 with decision making. In the running condition, choice reaction time (CRT), intelligence, and short-term memory, together with experience, correlated 0.46 with DM. These differences in cognitive abilities, as predictors of DM under walking and running conditions, are discussed in terms of information processing models and other cognitive processes. PMID- 8471995 TI - [Clinical factors which influence the 1-year post-infarction prognosis]. AB - Many clinical factors influence the 1-year prognosis in myocardial infarction (MI) patients. The most important clinical determinants are the left ventricular dysfunction, myocardial ischemia, and complex ventricular arrhythmias. Some authors have found an independent prognostic value of complex ventricular arrhythmias, while others consider that ventricular arrhythmias predict future cardiac events only if associated with low ejection fractions. Other factors that have 1-year prognostic value are the following: a previous MI, a history of angina at least 3 months preceding the infarct, postmyocardial angina, and the criteria that indicate to the practitioner whether MI patients are medically ineligible for stress testing. There still remain controversies in regard to the predictive value of certain variables such as the site, type, and extension of the MI, the presence of complex ventricular arrhythmias, exercise-induced hypotension, ST segment elevation, and the electrical provocation of dangerous arrhythmias. PMID- 8471996 TI - Fitness and lifestyle parameters fail to predict back injuries in nurses. AB - Performance on fitness and back related isometric strength tests, as well as the response to a lifestyle questionnaire, were related to the subsequent occurrence of back injuries in 119 nurses. In all, 22% of subjects sustained injuries during the 18-month study. Injured nurses were more likely to be from high-risk wards and to have received worker's compensation pay for past back injuries. Fitness and lifestyle characteristics did not differ significantly between injured and not-injured groups. Using backward stepwise logistic regression, a model was developed that accounted for 41% of the variability between groups and predicted 67% of those injured. Prior compensation pay, smoking status, and job satisfaction were the most useful discriminators. It was concluded, however, that the fitness and lifestyle parameters measured did not effectively predict back injury in nurses. PMID- 8471997 TI - Effects of jet lag on factors related to sport performance. AB - Three studies were performed to evaluate the effects of jet lag on factors associated with sport performance. In Study 1, members of the USA Women's Soccer Team traveled to Taiwan; in Study 2, North American students and faculty traveled to Western Europe; and in Study 3, European students traveled to North America. After travel, there was disruption of mood state and a reduction in dynamic strength; peak 5-s power and 30-s work capacity were reduced for 2 days (5-s power: 9.8 vs. 9.0 vs. 9.0 W.kg-1; 30-s work capacity: 213 vs. 199 vs. 201 J.kg 1). In these studies, mood state, anaerobic power and capacity, and dynamic strength were affected by rapid transmeridianal travel, and even highly trained athletes suffered from jet lag. However, effects of travel on the variables tested were essentially eliminated after 3 or 4 days. PMID- 8471998 TI - A survey of health sciences libraries in hospitals: implications for the 1990s. AB - In response to an expressed need for comprehensive data on health sciences libraries in hospitals, the American Hospital Association (AHA) conducted a survey of all U.S. registered hospitals in 1990. The response rate was 57%. Results showed that 2,167 hospitals (31.6% of all U.S. registered hospitals) had on-site libraries that met four definitional criteria. Survey results also indicated that hospitals use diverse resources and approaches to provide information services to a wide array of health care providers and consumers. These baseline data, combined with an assessment of key environmental factors affecting hospitals, can provide guidance to hospital libraries as they face the challenges of the 1990s. The AHA has added the health sciences library to services tracked in its annual survey of hospitals; additional research opportunities in this area remain. PMID- 8471999 TI - The future role of the health sciences library in the Department of Veterans Affairs. AB - The Department of Veterans Affairs (VA) conducted a survey to ascertain the perceptions of 322 library service chiefs and health care administrators within the VA health care system. Participants were asked to rate the desirability and probability of twenty-five predetermined statements and to identify the forces that would have an impact, either positive or negative, on whatever statements became reality. The response rate was 93%. Analysis of the data indicated that there was no significant difference between the library managers and health care administrators in their perceptions. Results indicate that both groups believe libraries serve an integral role in VA medical centers and that library services cannot be provided as successfully off site. The data also appear to reveal a clear consensus on the part of both groups for increased library involvement in educational activities and information delivery. PMID- 8472000 TI - Paraprofessional staff: a review and report on current duty assignment in academic health sciences libraries in North America. AB - This paper reviews paraprofessional employment in libraries and examines the trend toward assigning increasingly complex duties to academic library paraprofessionals. During the spring of 1989, directors of academic health sciences libraries in the United States and Canada were surveyed to determine the duties assigned to paraprofessionals. The results show that paraprofessionals are assigned a wide range of duties, including supervising functional areas, such as circulation and interlibrary loan, and some tasks often considered professional, such as original cataloging and in-depth reference work. The findings illustrate the importance of the paraprofessional to librarianship. PMID- 8472001 TI - Selected list of books and journals for the small medical library. AB - The potential for the hospital library as an accepted patient-focused module is viewed in terms of both the present and the future--or no future--in the introduction to this revised recommended list of 606 books and 143 journals. Predecessors of this list have been intended as selection guides for a small or medium-size library in a hospital or comparable medical facility. Due to rapidly rising prices, the secondary purpose--a basic collection for a consortium of hospital libraries or a network sharing library resources--may eventually become its primary use. Books and journals are categorized by subject; the book list is followed by an author/editor index, and the subject list of journals by an alphabetical title listing. For the first time, a "minimal core collection" consisting of 85 books has been broken out from the 200 asterisked initial purchase books. To purchase the entire collection of books and to pay for the 1993 subscriptions would require about $87,000; the cost of only the asterisked books and journals totals $34,800. The "minimal core list" of books costs $11,600. PMID- 8472002 TI - The UMLS project: making the conceptual connection between users and the information they need. AB - Conceptual connections between users and information sources depend on an accurate representation of the content of available information sources, an accurate representation of specific user information needs, and the ability to match the two. Establishing such connections is a principal function of medical librarians. The goal of the National Library of Medicine's Unified Medical Language System (UMLS) project is to facilitate the development of conceptual connections between users and relevant machine-readable information. The UMLS model involves a combination of three centrally developed Knowledge Sources (a Metathesaurus, a Semantic Network, and an Information Sources Map) and a variety of smart interface programs that make use of these Knowledge Sources to help users in different environments find machine-readable information relevant to their particular practice or research problems. The third experimental edition of the UMLS Knowledge Sources was issued in the fall of 1992. Current priorities for the UMLS project include developing applications that make use of the Knowledge Sources and using feedback from these applications to guide ongoing enhancement and expansion of the Knowledge Sources. Medical librarians are involved heavily in the direction of the UMLS project, in the development of the Knowledge Sources, and in their experimental application. The involvement of librarians in reviewing, testing, and providing feedback on UMLS products will increase the likelihood that the UMLS project will achieve its goal of improving access to machine-readable biomedical information. PMID- 8472003 TI - Coach: applying UMLS knowledge sources in an expert searcher environment. AB - With the development of the Unified Medical Language System (UMLS) Knowledge Sources, the National Library of Medicine (NLM) has produced a resource of great potential for improving the searching of MEDLINE. The Coach expert searcher system, an inhouse research project at NLM, is designed to help users of the GRATEFUL MED front-end software improve MEDLINE search and retrieval capabilities. This paper describes the Coach program, the knowledge sources it uses, and some of the ways it applies elements of the UMLS Metathesaurus to facilitate access to the biomedical literature. PMID- 8472004 TI - UMLS knowledge for biomedical language processing. AB - This paper describes efforts to provide access to the free text in biomedical databases. The focus of the effort is the development of SPECIALIST, an experimental natural language processing system for the biomedical domain. The system includes a broad coverage parser supported by a large lexicon, modules that provide access to the extensive Unified Medical Language System (UMLS) Knowledge Sources, and a retrieval module that permits experiments in information retrieval. The UMLS Metathesaurus and Semantic Network provide a rich source of biomedical concepts and their interrelationships. Investigations have been conducted to determine the type of information required to effect a map between the language of queries and the language of relevant documents. Mappings are never straightforward and often involve multiple inferences. PMID- 8472005 TI - Generic queries for meeting clinical information needs. AB - This paper describes a model for automated information retrieval in which questions posed by clinical users are analyzed to establish common syntactic and semantic patterns. The patterns are used to develop a set of general-purpose questions called generic queries. These generic queries are used in responding to specific clinical information needs. Users select generic queries in one of two ways. The user may type in questions, which are then analyzed, using natural language processing techniques, to identify the most relevant generic query; or the user may indicate patient data of interest and then pick one of several potentially relevant questions. Once the query and medical concepts have been determined, an information source is selected automatically, a retrieval strategy is composed and executed, and the results are sorted and filtered for presentation to the user. This work makes extensive use of the National Library of Medicine's Unified Medical Language System (UMLS): medical concepts are derived from the Metathesaurus, medical queries are based on semantic relations drawn from the UMLS Semantic Network, and automated source selection makes use of the Information Sources Map. The paper describes research currently under way to implement this model and reports on experience and results to date. PMID- 8472006 TI - Using a network menu and the UMLS Information Sources Map to facilitate access to online reference materials. AB - As computer technology advances, clinicians and biomedical researchers are becoming more dependent upon information from online databases and information systems. By using specially configured computer workstations and high-speed computer networks, it is now possible to access this information in a rapid and straightforward manner. To empower users by providing these capabilities, the authors are assembling a variety of network workstations to be located throughout Yale-New Haven Medical Center. At the heart of the workstation is NetMenu, a program designed to help users connect to a number of important online information systems, including a hospital order entry and results reporting system, a drug reference, bibliographic retrieval systems, and educational programs. In addition, as part of the National Library of Medicine's Unified Medical Language System (UMLS) project, the authors have developed a local prototype of the UMLS Information Sources Map (ISM) and a companion query assistant program to complement the NetMenu in helping users select and connect automatically to information services relevant to a particular question. The ISM query assistant draws from a listing of many online information sources accessible via local and international networks. PMID- 8472007 TI - The UMLS Metathesaurus: representing different views of biomedical concepts. AB - The UMLS Metathesaurus is a compilation of names, relationships, and associated information from a variety of biomedical naming systems representing different views of biomedical practice or research. The Metathesaurus is organized by meaning, and the fundamental unit in the Metathesaurus is the concept. Differing names for a biomedical meaning are linked in a single Metathesaurus concept. Extensive additional information describing semantic characteristics, occurrence in machine-readable information sources, and how concepts co-occur in these sources is also provided, enabling a greater comprehension of the concept in its various contexts. The Metathesaurus is not a standardized vocabulary; it is a tool for maximizing the usefulness of existing vocabularies. It serves as a knowledge source for developers of biomedical information applications and as a powerful resource for biomedical information specialists. PMID- 8472008 TI - The community-based database prototype of the southeast Florida AIDS Information Network. PMID- 8472009 TI - Use of MEDLINE by health sciences faculty at the University of Minnesota. PMID- 8472010 TI - A study of MeSH and UMLS for subject searching in an online catalog. PMID- 8472011 TI - AIDS literature underestimated. PMID- 8472012 TI - Journal supplements, libraries, and the FDA. PMID- 8472013 TI - Suppression of endotoxin mitogenicity of spleen cells by lipoxygenase inhibitors and its reversal by 13-hydroxyoctadecadienoic acid. AB - The effects of several inhibitors of lipoxygenases were investigated in murine spleen cell cultures activated with endotoxin (lipopolysaccharide). It was found that these inhibitors interfere with the proliferative response of the cultures. Indomethacin, a specific cyclooxygenase inhibitor, had no such effect. Endotoxin induced the synthesis of tumour necrosis factor alpha in spleen cells which was prevented by treatment with a lipoxygenase inhibitor. The inhibition of the mitogenic effect of endotoxin could be reversed by addition of 13 hydroxyoctadecadienoic acid. This was not the case with leukotriene B4 and C4 or 15-hydroxyeicosatetraenoic acid. In contrast, these substances had inhibitory effects on the mitogenicity of spleen cells. It is suggested that 13 hydroxyoctadecadienoic acid is involved in the development of the mitogenic reaction, possibly on the level of tumour necrosis factor alpha production of macrophages present in the cultures. PMID- 8472014 TI - Identification of Yersinia pestis with varied plasmid composition using monoclonal and polyclonal fluorescent immunoglobulins. AB - The efficiency of serological identification of Yersinia pestis strains which contain different plasmids was assessed with polyclonal and monoclonal immunoglobulin preparations in the direct fluorescent antibody method. Plague polyclonal luminescent immunoglobulins recognize only those Y. pestis strains which contain pPst, pFra plasmids or both. Anticapsular plague monoclonal antibodies interact only with capsule-forming plague agent strains (pFra+) grown at 37 degrees C. With plague monoclonal lipopolysaccharide antibodies one can identify all Y. pestis strains irrespective of their plasmid content and cultivation temperature. However, these antibodies cross-react with Yersinia pseudotuberculosis bacteria in 60% of cases. The problem of laboratory diagnosis of the plague organism, whatever its plasmid profile, can be solved through the development of a test kit involving two preparations such as plague lipopolysaccharide monoclonal luminescent antibodies and pseudotuberculosis specific luminescent adsorbed immunoglobulins. PMID- 8472015 TI - Inhibition of interleukin-6 release and T-cell proliferation by synthetic mirror pseudo cord factor analogues in human peripheral blood mononuclear cells. AB - The effects of synthetic alkyl ((alkyl 6-deoxy-a-D-gluco-heptopyranosyluronate) 6 deoxy-a-D-gluco-heptopyranoside) uronates, a novel type of mirror pseudo cord factor, on the in vitro modulation of interleukin-6 production and T-cell proliferation in human peripheral blood mononuclear cells, were investigated. Synthetic mirror pseudo cord factors with alkyl chains ranging from C16 to C18 have very weak interleukin-6-inducing capacities and lack mitogenic activities for T-cell proliferation. However, they could inhibit IL-6 release induced by sonicated Bacillus Calmette-Guerin (S-BCG), bacterial endotoxin, and phytohaemagglutinin in a dose-dependent manner. Inhibition was observed not only with mononuclear cells but also with purified monocytes. Furthermore, these synthetic compounds could suppress T-lymphocyte proliferation stimulated by sonicated Mycobacterium tuberculosis H37Rv (S-H37Rv) antigens, S-BCG antigens, as well as by recombinant 65 kDa mycobacterial heat-shock protein. In contrast, these compounds failed to inhibit the phytohaemagglutinin-induced T-cell proliferation. We conclude that the inhibition of cytokine release and T-cell proliferation by synthetic mirror pseudo cord factors was due to direct blocking of the function and/or activity of monocytes or antigen-presenting cells. PMID- 8472016 TI - Changing patterns of the IL-2/IL-2R pathway of lymphocyte activation following exposure to Plasmodium falciparum products: a study with squirrel monkey peripheral blood mononuclear cells. AB - Squirrel monkeys are experimental hosts useful for studies on human malaria. In the present work, in vitro lymphocyte reactivity was measured by proliferation in the presence of Plasmodium falciparum-derived products, and found to depend on the previous malarial status of the animals and upon the source and/or the nature of the P. falciparum-derived material. Special attention was given to the IL-2/IL 2R pathway of lymphocyte activation. Culture supernatant from P. falciparum parasitized erythrocytes exerted an inhibitory effect towards T lymphocytes obtained from P. falciparum-non-immune squirrel monkeys, when activated, for instance, by PHA. These lymphocytes did not incorporate tritiated thymidine (neither they did proliferate) although they expressed IL-2 alpha and beta binding chains and secreted IL-2 (or at least TCGF). This inhibitory effect could not be rescued by the addition of rhIL-2, although the assayed lymphocytes could retain the ability to continue their cell cycle progression and divide after removal of the P. falciparum-derived inhibitory product(s). The incidence of anti mitogenic molecules which impair the IL-2/IL-2R pathway of lymphocyte activation in malaria related processes is discussed. PMID- 8472017 TI - ESR dating of tooth enamel: comparison with U-series, FT and TL dating at the Peking man site. AB - Deer tooth samples from Zhoukoudian, the Peking Man Cave, were studied. Non linear fitting is used to determine AD, from which ESR ages were calculated by both the disequilibria model (DU) and linear uptake model (LU). Comparison of ESR ages with those from U-series, FT and TL methods show that the enamel of deer teeth is a suitable material for ESR dating. PMID- 8472018 TI - Kinetics of distribution of 5-doxylstearic acid in mouse lymphocytes. AB - The rate at which stearic acid nitroxide spin labels distribute through cells affects the interpretation of data obtained from these nitroxides. We used photoreduction of 5-doxylstearic acid (5DS) to determine the rate at which 5DS arrives at the outer half of the plasma membrane of mouse lymphocytes and macrophages. Our results show that 5DS is in equilibrium with the outer half of the plasma membrane of mouse lymphocytes over a time frame of 2 minutes or less. Thus, spectra data obtained from 5DS-labelled cells clearly reflects the spectrally averaged environment of all the cell membranes in lymphocytes and potentially other cells as well. This clarifies the observation that the spectral information obtained from doxylstearic acid nitroxides is relatively insensitive to environmental changes which would be expected to involve only the plasma membrane of the cell. PMID- 8472019 TI - Viral transformation of baby hamster kidney cells affects the oxygen sensitivity of nitroxide reduction. AB - In order to explore and expand the potential applications of nitroxides, it is important to understand how nitroxides are metabolized by living systems. We studied the oxygen sensitivity of a BHK (baby hamster kidney) cell line and BHK cells that had been transformed by adenovirus to determine if the process of adenoviral transformation affects nitroxide metabolism. When the BHK cells are transformed by adenovirus, they reduce nitroxides essentially independently of oxygen concentration. In addition, the rate of reduction of the nitroxides decreases by a factor of 10 compared to the rate of reduction in BHK cells. These data suggest to us that the process of viral transformation has affected dramatically the metabolism of these cells; one possible interpretation is that the viral transformed cells lost the ability to perform oxidative phosphorylation. We believe that this is a metabolic event which could be exploited by magnetic resonance imaging. PMID- 8472020 TI - Use of sugars and hair for ESR emergency dosimetry. AB - ESR spectrometry of sugars and biological samples is being evaluated for emergency personnel dosimetry. Sugars are near tissue-equivalent, universally available in pure form and produce a simple, reproducible, low background signal. Of the sugars tested, sucrose and dextrose are the most sensitive and the ESR signals are proportional to X- or gamma-ray doses over the range of 0.5-10 Gy. There is little dependence on radiation energy or dose-rate, and the ESR signals remain stable for long periods post-irradiation. Human hair samples show considerable variability and signal complexity creating difficulties in dose assessment. PMID- 8472021 TI - Synthesis and in vivo distribution in the rat of several fluorine-18 labeled 5 hydroxy-2-aminotetralin derivatives. AB - A method is described for the rapid production and purification of new potential dopamine agonists. Via thermal heating (refluxing in an oil bath) and microwave exposure 2-[N-n-3-fluoropropyl-N-(4-methylphenyl)ethylamino]-5-hydroxyte tralin (12), 2-[N-n-3-fluoropropyl-N-(4-fluorophenyl)ethylamino]-5-hydroxyte tralin (13), and their isotopic fluorine-18 derivatives were synthesized, respectively. The fluorine-18 label was introduced via N-fluoroalkylation with no-carrier-added (n.c.a.) 18FCH2CH2CH2I. In 115 min, radiochemical yields of 11% (corrected for decay) were achieved for both compounds. The specific activity ranged from 15-75 GBq/mumol. After i.v. injection in rats, the fluorine-18 labeled compounds were evaluated for their in vivo binding to the D2-receptors. The radioactivity levels in the striatum, nucleus accumbens and tuberculum olfactorius were not significantly higher than in the cerebellum and frontal cortex at 15, 30 and 60 min after administration of the tetralin derivatives. Dopamine depletion with reserpine did not affect the uptake in the dopamine D2-receptor rich area. Remarkable high uptakes were found in the adrenal for both compounds. PMID- 8472022 TI - Exposure-to-absorbed-dose conversion for human adult cortical bone. AB - The conversion of measured exposure to absorbed dose at a point in bone, under conditions of electron equilibrium, involves a factor (the f-factor) which is proportional to the ratio of the spectrum-averaged photon energy-absorption coefficient for bone to that for air. This paper gives mass energy-absorption coefficients and f-factors for three compositions of human adult compact or cortical bone recommended in publications by the ICRU and the ICRP, for photon energies from 1 keV to 1.5 MeV. Spectrum-averaged f-factors for a number of calibration x-ray beams ranging from 10 to 250 kVp have been calculated and compared to corresponding results obtained with the use of an equivalent photon energy derived from the measured thickness of the half-value layer. At low photon energies (approximately less than 200 keV), the new f-factor results reflect: (a) the rather large differences due to the differing calcium contents among the recommended compositions for bone: and (b) the generally poor predictions obtained when replacing a broad energy spectrum by an equivalent photon energy. PMID- 8472023 TI - Effective atomic number studies in different biological samples for partial and total photon interactions in the energy region 10(-3) to 10(5) MeV. AB - Effective atomic numbers (Zeff) of 7 different biological samples containing several elements were computed for total and partial cross sections using theoretical data over a wide range of energy region from 10(-3) to 10(5) MeV. It has been found that Zeff changes with change in composition of the material and change in energy. The significant changes in Zeff of different biological samples are due to domination of different interaction processes in different energy regions as number of elements present is quite large in some biological samples (e.g. cell, bone, muscle). PMID- 8472024 TI - Differentiation of elemental composition of normal and malignant breast tissue by instrumental neutron activation analysis. AB - Multi-elemental quantitative analyses of 15 paired samples of normal and malignant human breast tissue by instrumental neutron activation analysis are reported. The elements, Al, Br, Ca, Cl, Co, Cs, Fe, K, Na, Rb, Zn were detected. Significantly elevated concentration levels were found for Al, Br, Ca, Cl, Cs, K, Na, Zn in malignant compared to normal tissue. Although the role of elemental composition in breast cancer is unclear, this finding may be of importance as another parameter for differentiating normal from malignant tissue. PMID- 8472025 TI - Synthesis of 6-[18F] and 4-[18F]fluoro-L-m-tyrosines via regioselective radiofluorodestannylation. AB - The regioselective radiofluorodestannylation of 6-trimethylstannyl-L-m-tyrosine derivative 6 with [18F]F2 and [18F]acetyl hypofluorite afforded, after acid hydrolysis, 6-[18F]fluoro-L-m-tyrosine (8a) in radiochemical yields of 23 and 17%, respectively. Similarly, 4-[18F]fluoro-L-m-tyrosine (13a) was synthesized in 11% radiochemical yield from the corresponding 4-trimethylstannyl-L-m-tyrosine derivative 11 using [18F]F2. The structural analyses of precursors (6,11), intermediates, and the final products (after 18F decay), were carried out by 1H, 13C, 19F, 119Sn-NMR and high resolution mass spectroscopy. PMID- 8472026 TI - Production of no-carrier-added 199Au for gold cluster-labelled antibodies. AB - The production of no-carrier-added (NCA) 199Au by neutron activation of 198Pt was developed and the radiochemical separation of 199Au from Pt targets was investigated. Three different procedures, based on anion exchange in mixed solvent media, solvent extraction and extraction chromatography, are reported. The extraction chromatography method was superior in terms of yield (> 95%), Pt separation factor (< or = 10(-5)), and separation time (approximately 1 hr). This scheme has been used to successfully process large amounts (> 30 GBq) of 199Au, with an average specific activity of 7.59 GBq/micrograms (205 mCi/micrograms). PMID- 8472027 TI - No-carrier-added synthesis of meta-[131I]iodobenzylguanidine. AB - No-carrier-added meta-[131I]iodobenzylguanidine ([131I]MIBG) was prepared starting with two different metallated precursors. Attempted preparation of 3 (tri-n-butylstannyl)benzylguanidine was not successful. An alternate two-step strategy using 3-(tri-n-butylstannyl)benzylamine could be used to prepare radio iodinated [131I]MIBG in an overall radiochemical yield of 30-33%. Synthesis of [131I]MIBG via the radioiododesilylation of 3-trimethylsilylbenzylguanidine was also investigated. Yields were dependent on temperature, precursor concentration, solvent and nature of the oxidant. Radiochemical yields of 90% were obtained in 5 min at room temperature using either N-chlorosuccinimide or hydrogen peroxide in trifluoroacetic acid as oxidants. The percentage of specific binding in vitro of no-carrier-added MIBG to SK-N-SH neuroblastoma cells remained constant over a 2 log activity range, while the binding of MIBG prepared by isotopic exchange dropped by a factor of seven. In normal mice, heart and adrenal uptake of no carrier-added [131I]MIBG was found to be higher than that of [131I]MIBG prepared by isotopic exchange. PMID- 8472028 TI - [15O]H2O, [15O]O2 and [15O]CO gas production, monitoring and quality control system. AB - The 15O gas production system selects the gas production mode, monitors gas delivery conditions and performs quality control needed during the production and delivery of continuous flow radioactive gas for equilibrium and bolus PET studies. Target gas switches choose the appropriate valve positioning for [15O]H2O, [15O]O2 or [15O]CO production while flow rate, pressure and radioactivity are constantly monitored. The system also includes an IBM PC interfaced gas chromatograph which provides chemical and radiochemical quality control by on-line, real time, gas sampling of the delivery line. PMID- 8472029 TI - Synthesis of [11C]tetrabenazine, a vesicular monoamine uptake inhibitor, for PET imaging studies. AB - Tetrabenazine (TBZ), a high affinity and specific inhibitor of the vesicular monoamine transporter, has been labeled with carbon-11 as a potential probe for in vivo positron emission tomographic imaging of monoaminergic neuronal losses in neurodegenerative diseases. [11C]TBZ was synthesized by O-[11C]methylation of the 9-O-desmethylTBZ using [11C]methyl iodide in the presence of tetrabutylammonium hydroxide. The radiochemical yields were 35-55% (decay corrected) and the synthesis time 32-37 min from EOB. [11C]TBZ was obtained with specific activities of 2000-2500 Ci/mmol (EOS) and radiochemical and chemical purities were > 95%. [11C]Tetrabenazine is a promising new radioligand for the in vivo study of monoaminergic neurons using PET. PMID- 8472030 TI - Rapid radiochemical and chemical quality control of [11C]putrescine. AB - A short (4.6 x 50 mm) cation exchange column was used in conjunction with conductivity and radioactivity detectors to determine the radiochemical purity (> 99%) and specific radioactivity (0.5-1.0 Ci/mu mol) of [1-11C]putrescine prepared via Michael addition of [11C]cyanide to acrylonitrile. The absence of acrylonitrile, a rodent carcinogen, from the final preparation was verified at the 50 ng level capillary vapor-phase chromatography (VPC) using a nitrogen phosphorus detector. Routine VPC analysis using a Poropak Q column and flame ionization detection showed that preparations contained no more than 1 microgram of acrylonitrile. PMID- 8472031 TI - Spatial dose-rate distribution for an 194Ir point source in water. AB - The spatial dose-rate distribution arising from a unit activity point source of 194Ir embedded in an infinite water medium has been calculated. These results may prove to be both useful and timely; 194Ir is a beta-particle-emitting radionuclide that is a suitable candidate for radioimmunotherapy, and a means for producing it fairly easily has recently been made available. Calculation of the beta-ray dose-rate distribution is based on a new set of monoenergetic electron dose point kernels which are results from an improved Monte Carlo (ETRAN) calculation. The spatial dose-rate distribution for 32P was also calculated and compared with results from the EGS4-PRESTA and ACCEPT Monte Carlo codes. The ETRAN-based distribution agrees with that from EGS4-PRESTA to within 2% out to 3.6 mm from the source, a distance over which 90% of the source energy is deposited. The ETRAN-based distribution also agrees well with that from ACCEPT between 0.6 and 4 mm from the source; at distances < 0.6 mm, values from ACCEPT are about 6% larger than ones calculated here. PMID- 8472032 TI - Urgent issues in public health. PMID- 8472033 TI - Urology at Kings County Hospital, Brooklyn. A 25 year experience, 1958-1983. PMID- 8472034 TI - Overview of sclerostomy. PMID- 8472035 TI - Surgical management of carcinoma of the esophagus. PMID- 8472036 TI - Advances in functional restoration. PMID- 8472037 TI - Benzene, artificial leather and aplastic anemia: Newark, 1916-1928. PMID- 8472038 TI - On entering medicine. PMID- 8472039 TI - Patterns of alcohol use and abuse among aging Civil War veterans, 1865-1920. AB - Given the extent of alcoholism among elderly people, it is remarkable how little is known about the biomedical and social dimensions of alcohol use and abuse in late life. In the absence of compelling longitudinal data drawn from contemporary sources, a historical perspective may help to illuminate the incidence and consequences of alcohol abuse among the elderly. Based on a study of 370 case histories drawn from the National Military Home in Dayton, Ohio, which around the turn of the century was the nation's largest old-age home, it appears that alcohol's social ramifications were more important than its pathological or physiological manifestations in late 19th-century America. Drinking habits among aging Civil War veterans varied considerably: moderate consumption was acceptable; too much of a good thing caused problems. PMID- 8472040 TI - Family-centered perinatal education. AB - Family-centered perinatal education is a health education service focused on the family unit during the childbirth period and is supportive to all family members as the family moves from one stage of development to the next. It is distinct from traditional childbirth education and family-centered maternity care by being a single educational intervention that addresses the needs of the entire family during the prenatal and postpartum periods. The advantages of family-centered perinatal education are discussed from the consumer's and educator's perspectives. Such education emphasizes extending social support into the postpartum period as a buffer against the effects of stress on new parents. Teaching and learning occur in a more timely manner. Family members learn what is most needed when it is most needed and avoid the feeling of being "cut loose" from the health care system right after the birth. Family-centered perinatal education is likely to become an increasingly popular consumer option as hospitals compete to provide the best obstetric/neonatal care. PMID- 8472041 TI - Childbirth education classes in homeless shelters. AB - Childbirth education can have an enormous positive effect on the maternal health and birth experience of women in shelters. The childbirth educator can empower economically disadvantaged pregnant women to take personal responsibility for their childbirth outcome. The characteristics of women in shelters pose unique challenges to childbirth educators. Transient populations, different stages of pregnancy, substance abuse, nutrition deficiencies, and difficulties with the skills required for being a good parent present unusual problems and rewarding educational opportunities. With understanding, sensitivity, and commitment, the childbirth educator can prepare women in shelters to participate more actively in a healthy and informed birth experience. PMID- 8472042 TI - Prenatal education in the work place. AB - Advances in neonatal care have improved survival rates among premature and low birth-weight (LBW) infants, but highly technical care for these infants costs more than $2 billion a year in the United States. The incidence of premature and LBW infants can be reduced by prenatal education programs that focus on nutrition, obtaining prenatal care, avoiding dangerous substances, and recognizing preterm labor. In an effort to contain health care costs, many companies self-insure employee health benefits and offer health promotion programs designed to improve life style behaviors. This article examines providing a prenatal education program in the work place as a way of reducing the incidence and costs of prematurity and low birth weight. PMID- 8472043 TI - Sibling preparation classes. AB - A review of the recent literature substantiates that sibling preparation classes help to ease the transition into being a sibling. Studies have shown that as a result of this preparation, children who become siblings exhibit fewer anxieties, are better able to express their feelings, and the mother feels better able to cope with the older child when the infant arrives. This article presents a detailed description of one hospital-based sibling preparation class: the setup, arrival of the families, tour of the maternity floor, snack and video presentation, and the separation into a children's class with specific objectives and a parents' class with objectives are presented. A description of other models of sibling preparation classes is included. PMID- 8472044 TI - Perinatal education for women with physical disabilities. AB - Pregnant women with disabilities have many of the same concerns as able-bodied pregnant women. However, pregnant women with disabilities have special perinatal education needs. Information on the problems encountered and approaches that can be used is presented based on current research and interviews with 36 childbearing women with disabilities. PMID- 8472045 TI - Perinatal education for parents of high-risk infants. AB - This article presents research-based information about the teaching needs of parents of low-birth-weight, preterm infants. An overview is presented regarding who needs to be taught, at what times, and in what manner. The type of information that parents have stated they found important is reviewed, as are general categories of information that health care providers feel are important for families to know. Family teaching is a critical component of the care nurses give because it helps to ensure that families are able to care for their infants at home. PMID- 8472046 TI - Critical dimensions in perinatal education. AB - A commitment to family-centered care demands that perinatal education include the following critical dimensions: presenting information, enhancing coping strategies, fostering support systems, promoting informed decision making, and integrating consumer advocacy. Families must have accurate, current information about pregnancy, birth, infants, early parenting, and the health care system in which these vents occur. This information is the foundation, not the final product, of perinatal education. Families need appropriate and effective coping skills and a strong support network as they move through this stage of the life cycle. The ultimate goal, and perhaps the most critical dimension of perinatal education, is to promote informed decision making. Families need options and the opportunity to understand the implications and feasibility of alternative decisions in their lives. The perinatal educator acts as an advocate by providing information and support for the client, and in advocating for the client in the health care system. PMID- 8472047 TI - Strengthening family systems. AB - The childbearing year is a psychosocial transition that involves changes in roles and status for each member of the family. This change is perhaps most significant in the transition that occurs with the birth of the first child. Thus, childbirth education can be looked upon as an opportunity to strengthen family systems through anticipatory guidance and skill building that family members may use throughout the life cycle. PMID- 8472048 TI - Developing a perinatal education program. AB - The process of assessing learning needs and designing and implementing educational offerings for perinatal families is discussed. Common areas of evaluation are examined, and sample questions are presented. Through careful application of teaching principles in conjunction with the nursing process, nurses can effectively develop comprehensive perinatal education programs. PMID- 8472049 TI - A comprehensive perinatal education program. AB - Perinatal education has become a common standard of preparation for expectant families anticipating childbirth and support for new families during the transition into parenthood. Twenty-two series and classes are defined and a topical outline is provided for a specific audience of clients, including infants, preschoolers, expectant parents, new parents, and grandparents. PMID- 8472050 TI - Issues in perinatal education. AB - There are three critical issues in perinatal education today: changing clients, changing perinatal educators, and the changing obstetrical climate. Each of these issues is discussed, and difficult philosophical questions that require answers are identified. The answers will require serious deliberation, hard thought, values clarification, collective wisdom, and an element of risk taking by perinatal educators. PMID- 8472051 TI - Preconceptional education. AB - Recently, attention has been given to the area of preconceptional health education and promotion of improved pregnancy outcomes through risk assessment and planning. This article identifies successful teaching strategies for preconceptional health education by health care providers and identifies class content and methods for preconceptional health education, with an emphasis on the interdisciplinary team approach. PMID- 8472052 TI - The psychoeducational model of prepared childbirth education. AB - Prepared, childbirth education classes are designed to teach the expectant mother how to effectively cope with the childbirth experience through active participation, informed decision making, and noninvasive pain management skills. As knowledge and technology increase, it often becomes difficult for the childbirth educator to complete the important task of determining the essential content for each class. The childbirth educator can follow established guidelines for class content with a review the literature or structure the class to meet the needs of the participants. An approach used less often, but a powerful and effective one, is using a conceptual model as a framework for selecting the essential content for classes. PMID- 8472053 TI - School-based adolescent pregnancy classes. AB - School-based adolescent pregnancy classes provide the childbirth educator with a unique opportunity to be visible to students. Attitudes about sexuality and pregnancy can be changed within the mainstream population by the presence of prepared childbirth classes at schools. The problems of absenteeism and denial of pregnancy that result in late reporting to health care providers can be minimized. The expectant teen-ager can be encouraged to attend school and given self-confidence in assuming the role of a parent after birth. Support can be engendered from faculty, students, and the teen-ager's support person. PMID- 8472054 TI - Outreach childbirth education classes for low-income families: a strategy for program development. AB - Childbirth and parenting education programs are coming to the forefront of public health initiatives aimed at the reduction of infant mortality and low birth weight in high-risk groups in the United States. Childbirth education programs have proven effective in helping parents make positive life style changes and can play an important role in the reduction of risks associated with poor pregnancy outcomes. Childbirth education gives parents the knowledge, desire, and confidence they need to change their health behaviors. The Florida Outreach Childbirth Education Project offers an example of a statewide program designed to serve a high risk population: low-income, low-literacy families. PMID- 8472055 TI - Our new journal. Why? PMID- 8472056 TI - Effects of aerosolized pentamidine in AIDS patients. PMID- 8472057 TI - Effect of long-term therapy with oral steroids on respiratory muscle function and ventilatory drive. AB - It has been shown that chronic oral steroid therapy (ST) does not induce respiratory muscle dysfunction in normal and asthmatic subjects. As corticosteroids are sometimes chronically used in the treatment of the patients with chronic obstructive pulmonary disease (COPD), the aim of our study was to verify whether ST could cause respiratory muscle impairment and, since ST also affects the central nervous system, whether ST could influence the ventilatory pattern. We retrospectively studied 12 COPD patients (group A), on long-term therapy (for at least 4 consecutive months, range 4-18 months) with an oral steroid, deflazacort, 15 mg.d-1. The subjects were strictly matched, with regard to age, sex, height, weight, forced expiratory volume in one second (FEV1), residual volume (RV), arterial oxygen tension (PaCO2), arterial carbon dioxide tension (PaCO2) and pH, with 12 COPD patients (Group B) who had never taken oral steroids. To assess respiratory muscle strength, we measured maximal inspiratory (MIP) and expiratory (MEP) pressures, while mouth occlusion pressure (P0.1) was employed to assess neuromuscular drive; ventilatory pattern and airway impedence were also evaluated. Effectiveness of ST was confirmed by the plasmatic levels of endogenous cortisol. No significant differences were observed between the two groups with regard to MIP (A 72.2 +/- 9.7 vs B: 70 +/- 7.2 cmH2O) and MEP (A 91.6 +/- 10.5 vs B 94.4 +/- 7.6 cmH2O) whilst P0.1 was significantly higher in group A (2.6 +/- 0.3 cmH2O) than in group B (1.8 +/- 0.1 cmH2O). No significant differences were found among all the ventilatory parameters, but the impedence was significantly higher in group A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472058 TI - Peak expiratory flow monitoring and airway response to specific bronchial provocation tests in asthmatics. AB - To assess the validity of peak expiratory flow (PEF), measured by means of a peak flow meter, in comparison to forced expiratory volume in one second (FEV1) for measuring the airway response during specific bronchial challenges, we registered PEF and FEV1 in a random sequence during 75 positive (decrease in FEV1 of > or = 15% from baseline) and 75 negative (decrease in FEV1 < 15% from baseline) challenges with chemicals or allergens. The correlation between PEF and FEV1 in terms of absolute values and of percentage of change from baseline was statistically highly significant (p < 0.001) in all challenges and in the different pattern of response, immediate, dual and late. Relative operating characteristic analysis showed that an absolute decrease in PEF of > or = 70 l.min-1 in the immediate and of > or = 80 l.min-1 in the late phase of the response (cut-off points) gave optimal discrimination between challenges with a bronchoconstrictive response (defined as a FEV1 decrease > or = 15% from baseline), and challenges without. These cut-off points, however, were highly specific (92 and 93.3%, respectively), but not as sensitive (70.6 and 61.1%, respectively), and smaller absolute changes in PEF from baseline do not exclude a bronchoconstrictive response. Our data suggest that PEF readings are a useful diagnostic tool in assessing the airway response during a specific bronchial challenge in asthmatics, although with some limitations. PEF readings can be used to monitor the late response to a challenge during the evening and the night if PEF readings are carefully considered in relation to clinical symptoms. PMID- 8472059 TI - Thymomodulin enhances phagocytic and intracellular killing activities of polymorphonuclear leucocytes without increasing release of chemotactic factors. AB - Thymomodulin, a calf thymus derivative, is able to stimulate T-lymphocytes and monocytes, and to activate phagocytes and their precursors. However, it is not fully understood whether the effect of thymomodulin on phagocytic cells is a direct stimulation, or a phenomenon mediated by cytokines released by mononuclear cells. To answer this question, we first evaluated the effects of thymomodulin on the phagocytosis and intracellular killing of Staphylococcus aureus by blood polymorphonuclear cells (PMNs), cultured with or without autologous mononuclear cells. Secondly, during the processes of phagocytosis and intracellular killing, we evaluated the release by PMNs of chemotactic factors for PMNs, lymphocytes and monocytes. No difference was found in the phagocytosis and killing processes when PMNs were incubated alone or with autologous mononuclear cells (p > 0.05, each comparison). Thymomodulin was able to increase the phagocytosis process when PMNs were incubated with lymphocytes and monocytes (p = 0.05), and to enhance the killing by PMNs cultured alone (p = 0.05), or cultured with autologous mononuclear cells (p < 0.05). The release of chemotactic factors for PMNs, lymphocytes and monocytes in the supernatants of the phagocytosis experiments, was higher when PMNs were incubated with mononuclear cells, compared to cultures of PMNs alone (p < 0.05, each comparison); and thymomodulin did not increase their release without the presence of autologous mononuclear cells in the cultures (p > 0.05 each comparison). These data suggest that thymomodulin acts upon PMNs, inducing mononuclear cells to release factors able to stimulate the phagocytosis and the intracellular killing of exogenous organisms, but does not amplify the immune reaction enhancing further leucocytes recruitment. PMID- 8472060 TI - A case of Churg-Strauss syndrome. PMID- 8472062 TI - Home ventilation. PMID- 8472061 TI - Central alveolar hypoventilation in a seven year old boy. Long-term treatment by nasal mask ventilation. PMID- 8472063 TI - Patient selection and techniques for home mechanical ventilation. European Respiratory Society Rehabilitation and Chronic Care Scientific Group. PMID- 8472064 TI - The carotid body: a review of its anatomy, physiology and clinical importance. AB - The carotid body is a peripheral chemoreceptor that monitors arterial blood gas tensions and pH. Its main function is to contribute to the regulation of breathing although there is evidence for a reflex influence on the pulmonary circulation and the kidney. The carotid body's acute response to hypoxia is a rapid increase in breathing. The chronic response to hypoxia such as would occur at high altitude or as a consequence of COPD, includes growth of the organ, both hyperplasia and hypertrophy, modification of amine content and an attenuation of its hypoxic sensitivity. It is the latter aspect that may cause severe problems of management of COPD for the clinician. It is postulated that the attenuated hypoxic sensitivity may play a role in the deterioration of the COPD patient. PMID- 8472065 TI - Role of bronchial and bronchoalveolar lavage in chronic obstructive lung disease. AB - The authors review the role of bronchoalveolar and bronchial lavage in chronic obstructive lung disease patients. Only a few papers were published in the last ten years on this matter. In addition, data are incomplete and often conflicting, mainly because of the limited number of patients sampled and of non-standardized techniques of analysis. However, both bronchoalveolar and bronchial lavage are likely to be useful research tools to understand the pathophysiologic mechanisms underlying chronic obstructive lung disease. PMID- 8472066 TI - A section on education: why? PMID- 8472067 TI - Respiratory function in neuromuscular and chest wall diseases. PMID- 8472068 TI - Classification of chest wall diseases. AB - Several disorders of the thoracic cage are known to cause respiratory failure, by means of relatively simple mechanisms, such as the increased work of breathing, which results in alveolar hypoventilation. A variety of pathogenic mechanisms may be considered, as functions of the types of thoracic disorders present. As causes of these additional potential mechanisms, we considered the following: 1) ventilation-perfusion (V/Q) inhomogeneity; 2) inability to cough; 3) malformation or acquired defect of the respiratory centres; and 4) excess blood volume and fluid retention, which aggravate work of breathing and V/Q inhomogeneity. All of these disorders can be grouped into two major categories (which nevertheless have some of the pathophysiology in common): the mechanical syndrome and the neuromuscular or paralytic syndrome. In this paper we discuss chest wall diseases falling into the first category; namely, kyphoscoliosis, fibrothorax, thoracoplasty, ankylosing spondylitis and obesity-hypoventilation. Congenital deformities of the thoracic cage, which do not have important effects on ventilatory apparatus (e.g. pectus excavatum and pectus carinatum), were also considered. PMID- 8472069 TI - Respiratory mechanics in kyphoscoliosis. AB - Kyphoscoliosis is a restrictive respiratory disorder in which total respiratory and lung elastances and lung resistance are increased. Specific airway conductance is increased because of greater lung elastic recoil. Corrective surgical procedures usually result in further immediate increases beyond that related to anaesthesia alone. Despite thoracic deformities, kyphoscoliotics maintain near-normal ventilation through increased central drive, and compensatory mechanisms including force-length and force-velocity properties of contracting inspiratory muscles, the Hering-Breuer reflex, inspiratory duration and airflow. The magnitude of compensation to loading in kyphoscoliotics is proportionately the same as in normal subjects. A recent study has shown that post-inspiratory muscle activity in anaesthetized kyphoscoliotics is proportionate to the magnitude of elastic recoil and intrinsic flow resistance. Expiratory decay may also be influenced by viscoelastic behaviour of thoracic tissues and the transition between their passive and active state. PMID- 8472070 TI - Respiratory mechanics in chest wall disease: implications for expiratory flow limitation during resting breathing. AB - Expiratory flow limitation during tidal breathing in patients with severe obstructive pulmonary disease is a well recognized phenomenon. It may be present, however, also in patients with severe chest wall disease due to the fact that breathing takes place at reduced lung volume. PMID- 8472071 TI - Control of breathing in chest wall diseases. AB - Chest wall diseases are characterized by an increased stiffness of the chest wall, and require more respiratory work to be done to ventilate the lungs adequately. We have reviewed the responses of the respiratory system for compensate for these mechanical loads: intrinsic (muscular) adaptation and central drive (extrinsic) adaptation. In ankylosing spondylitis, there is an efficient intrinsic adaptation, mostly by the diaphragm, with good respiratory prognosis. It is likely that eucapnic obese patients have a normal adaptation of respiratory drive, whereas the failure of the control of breathing may lead to obesity hypoventilation syndrome. In kyphoscoliosis, normal gas exchange is assumed by an increased muscular contribution, and so depends on an increased neural drive. However in major chest distortion, a failure of this neuromuscular compensation may occur and be responsible for life threatening episodes. PMID- 8472072 TI - Control of breathing in patients with neuromuscular diseases. AB - We reviewed the studies devoted to investigate the control of breathing in patients with neuromuscular diseases. Neural respiratory drive has been assessed in terms of minute ventilation and mouth occlusion pressure (P0.1) in patients with several types of neuromuscular affections (amyotrophic lateral sclerosis, poliomyelitis and post-polio syndrome, Guillain Barre syndrome, muscular dystrophies, inflammatory muscle diseases). More recently we have used electromyographic activity of diaphragm to evaluate neural drive in patients with myasthenia gravis and muscular dystrophies. The results of these studies seem to indicate that patients with myasthenia gravis are not likely to have a decreased respiratory drive, the disorder in neuromuscular transmission being probably the reason for the apparent decrease in diaphragmatic neural activation during hypercapnic stimulation. Increase in neural afferent information from lung and/or rib cage might explain both the increased neural respiratory drive and the faster breathing observed in patients with neuromuscular disease. PMID- 8472073 TI - Evaluation of human diaphragm function. AB - When single supramaximal shocks are delivered during relaxation to both phrenic nerves simultaneously, the resulting transdiaphragmatic pressure twitch (PdiT) or mouth pressure twitch (PmT) are found to decrease linearly with increasing lung volume thereby reflecting changes in diaphragm contractility. Whereas fatigue decreases PdiT at any given lung volume, chronic lung hyperinflation tends to increase PdiT at any given lung volume. When the phrenic nerve shocks are delivered during ongoing voluntary contractions, PdiT decreases with increasing level of diaphragm activation. Its amplitude thus detects the reverse left for full activation of the diaphragm by the voluntary motor drive. The ability to maximally activate the diaphragm decreases with fatigue but is retained in patients with chronic lung hyperinflation. PMID- 8472074 TI - Mechanisms of muscle fatigue. AB - The concept of muscle fatigue as a factor limiting muscle performance has evolved into one in which fatigue is avoided in order to protect the muscle from injury induced by over stimulation. No one mechanism accounts for all the changes in muscle performance occurring during fatigue. Research on pathophysiological factors limiting force production or shortening capacity during the fatigue process has widened to detailed electrophysiologic, metabolic and molecular aspects. All are extensively reviewed in the present paper. The known mechanisms are likely to be interdependent, synergistic, and integrated. A careful interpretation of individual research is implied, particularly when data from experimental animal models are translated to human beings. PMID- 8472075 TI - Exercise-induced asthma. PMID- 8472076 TI - Physical therapy management of patients undergoing limb lengthening by distraction osteogenesis. AB - Limb lengthening by distraction osteogenesis and external fixation is used increasingly in the United States for a variety of orthopaedic conditions. Maintenance of joint motion, critical for successful outcomes, can be difficult to achieve. The rate of growth needed for distraction osteogenesis is faster than that of normal growing bone. Histogenesis of soft tissues must also occur to maintain the motion in joints above and below the limb being lengthened. Physical therapists in patients' home communities need to be knowledgeable about the aggressive management needed to prevent the loss of joint motion. This article introduces physical therapists to a commonly used external fixator, the procedure of distraction osteogenesis, and the role of functional loading. To assist in treatment planning, a physical therapy management plan is presented. Two case examples illustrate how therapists can assess a patient's status relative to the goals in the management plan and determine intervention priorities. PMID- 8472077 TI - Effect of knee angle and ligament insufficiency on anterior tibial translation during quadriceps muscle contraction: a preliminary report. AB - Additional information is needed regarding the effects of exercise protocols on the injured or reconstructed anterior cruciate ligament (ACL). The purpose of this investigation was to assess the effects of knee flexion angle and ACL insufficiency on anterior tibial translation (ATT) and patellar ligament insertion angle as subjects performed maximal isometric quadriceps muscle contractions. The subjects were two females and two males between the ages of 18 and 24 who had sustained injuries that resulted in unilateral ACL insufficiency. Each subject performed maximum isometric quadriceps muscle contractions with each leg on a Cybex II dynamometer at each of three positions: 15, 45, and 75 degrees knee flexion. A lateral knee roentgenogram was obtained as each subject maintained each isometric muscle contraction. A roentgenogram also was taken as subjects rested each knee in each of the three target positions. Anterior tibial translation for each isometric muscle contraction was assessed by measuring the anterior displacement of the tibial plateau on the isometric resisted roentgenogram relative to the resting roentgenogram. Patellar ligament insertion angle also was measured for each roentgenogram. Maximum ATT occurred at the 15 degrees knee flexion target angle for two subjects and at the 45 degrees target angle for the other two subjects. Patellar ligament insertion angle decreased as knee flexion angle increased. Appreciable stress may be imposed on the ACL as patients perform maximum quadriceps muscle contractions in positions of terminal knee extension and in midrange positions previously reported as being safe for maximal effort quadriceps exercise. Magnitude of stress imposed on the ACL is discussed as a function of the length-tension relationship of the quadriceps muscle-tendon unit and insertion angle of the patellar ligament. Suggestions are made for additional research regarding appropriate muscle strengthening protocols for patients who have undergone ACL reconstruction. PMID- 8472078 TI - Iliotibial band tightness and medial patellar glide in patients with patellofemoral dysfunction. AB - This paper investigates the relationship between iliotibial band tightness and medial glide of the patella in patients with patellofemoral dysfunction. Stretching the iliotibial band has been advocated in the literature to treat patellofemoral dysfunction, but there is little written about the mechanism of its influence on the patella. Anatomy and biomechanics are reviewed, with emphasis on the lateral retinaculum of the knee and the attachment of the iliotibial band to the patella. A study is presented in which 17 patients with patellofemoral dysfunction were evaluated. All patients presented with lateral tracking of the patella on knee flexion and extension. Medial glide of the patella was tested manually, and Ober's Test was performed to test flexibility of the iliotibial band. Twelve of 17 patients exhibited a tight iliotibial band with hypomobility of medial glide of the patella. Three patients demonstrated normal patella mobility with a normal result on Ober's Test. Two patients had hypomobile patellae with a normal Ober's Test. This study demonstrates a strong relationship between iliotibial band tightness and decreased medial glide of the patella. PMID- 8472079 TI - Effect of the aircast on unilateral postural control: amplitude and frequency variables. AB - Little objective data exist regarding the effect of the Aircast Air-Stirrup on motor performance. Thus, the effect of the Aircast on the amplitude and frequency of postural sway during unilateral stance was evaluated for 15 uninjured male subjects. Postural sway during static and dynamic tests was measured using the Chattecx Balance System. Use of the Aircast improved unilateral postural control as evidenced by decreases in some of the components of postural sway. Previously, a link was made between a large amplitude of unilateral sway and a high probability of ankle injury (14). Thus, since Aircast use was found to decrease the amplitude of unilateral sway, it may also be beneficial in reducing the probability of injury. Although the scope of this study did not allow for differentiation among the complex systems involved in postural control, the possibility of the Aircast enhancing afferent feedback was proposed. The restricted inversion-eversion range of motion associated with the Aircast, in conjunction with the present observation that unilateral stability was enhanced with its use, suggests that the Aircast may provide a valuable prophylactic role in helping to reduce the incidence of ankle injuries. PMID- 8472080 TI - Reliability of measuring forward head posture in a clinical setting. AB - We believe there is a need to identify a practical method for determining objective measurement of forward head posture. In our study, we determined the within-tester and between-tester reliabilities for clinical measurements of static, sitting, forward head posture using the cervical range of motion (CROM) instrument. Repeated measurements were made using a standardized protocol on 40 patients seated in a standardized position. The seven testers had from 1 to 8 years of clinical experience. All measurements were recorded by the same investigator. The intraclass correlation coefficient (ICC[1,1]) was used to quantitate within-tester and between-tester reliability. Measurements of forward head position performed by the same physical therapist had high reliability (ICC = 0.93). Good reliability (ICC = 0.83) was demonstrated when different physical therapists measured the forward head posture of the same patient. We concluded that measurements of forward head posture made by physical therapists trained in the correct use of the CROM instrument are reliable. This reliability is important for determining the effectiveness of treatment programs. On the basis of our data, the CROM instrument will assist clinicians in the objective evaluation and reassessment of the patient population demonstrating forward head posture. PMID- 8472081 TI - Retaining the health regions--strategic direction or deregulation? PMID- 8472082 TI - Minimally invasive surgery in gynaecology--trick or treat? PMID- 8472083 TI - Operative laparoscopy. AB - The past decade has witnessed a transition from classic surgery to minimally invasive surgery through multiple small incisions under endoscopic vision. Although these operations present many technical difficulties and often take longer, they usually reduce the hospital stay and allow earlier return to full activity. PMID- 8472084 TI - Vasovagal syncope: classification, investigation and treatment. AB - Syncope is a common and often difficult clinical problem. Head-up tilt testing has made it possible to confirm the diagnosis of vasovagal syncope in many patients with unexplained loss of consciousness. This review outlines its presentation and mechanism, the methodology of diagnostic tilt testing and current treatments. PMID- 8472085 TI - Acoustic schwannoma. AB - Acoustic schwannomas are the commonest tumours of the cerebellopontine angle and usually present with unilateral deafness. Earlier diagnosis while the tumour is small, coupled with surgical treatment by a specialized neuro-otology team, has contributed to a significant decrease in the mortality and morbidity due to these tumours. PMID- 8472086 TI - Guidelines for the management of community-acquired pneumonia in adults admitted to hospital. The British Thoracic Society. AB - Around 50,000 people in the UK are admitted to hospital with pneumonia, making it one of the commonest causes of admission. This article presents guidelines drawn up by the British Thoracic Society to improve the care delivered to such patients in the UK. PMID- 8472087 TI - What should a clinical director do? AB - Clinical directors play an important role in developing service strategy and in the introduction of systems needed to generate efficiency and improve quality in health care delivery in their provider units. This article emphasizes the range of abilities needed to succeed as a clinical director. PMID- 8472088 TI - Clinical directorates: the new order. AB - Doctors now accept that they must play a leading role in the management of hospitals. Clinical directorates embrace a range of managerial responsibilities on behalf of colleagues and for the benefit of the organization. PMID- 8472090 TI - Changes in terminology serve no useful purpose. PMID- 8472089 TI - Depressive stupor following amphetamine withdrawal. PMID- 8472091 TI - The acontractile bladder and retention in women. PMID- 8472092 TI - Time to ensure a better deal for RA patients. PMID- 8472093 TI - The trouble with technology. PMID- 8472094 TI - Doctors learning about epilepsy. PMID- 8472095 TI - Thinking clearly about diseases of the airways. PMID- 8472096 TI - Medical training and the EC. PMID- 8472097 TI - Atherosclerotic renal artery stenosis. AB - Atherosclerotic renal artery stenosis is a relatively common cause of hypertension and renal impairment in the elderly. We review its clinical features and the investigations and management options available. PMID- 8472098 TI - Transmissible spongiform encephalopathies and human neurodegenerative disease. AB - There has been a tremendous amount of publicity concerning the transmissible spongiform encephalopathies, and this has led to speculation regarding the possible risk to humans following the emergence of new forms in cattle and cats. We review the data relating to these diseases in the light of new developments, particularly in the fields of molecular biology and epidemiology. PMID- 8472099 TI - The role of cytokines in normal and pathological bone states. AB - Cytokines have been increasingly implicated in the pathogenesis of many of the common proliferative and degenerative diseases. This review outlines the rapidly expanding field of cytokines and discusses their role in bone metabolism and bone and joint diseases. PMID- 8472100 TI - Medical photography. AB - Medical photography and illustration still provides an essential service for the clinician and researcher, despite an ever-increasing remit. This article describes the role of the medical illustration department and may help the hospital practitioner to use this service to the full. PMID- 8472101 TI - Boot-shaped heart. PMID- 8472102 TI - Systemic fungal infections in neonates. AB - The 50,000 or so known species of fungi are present in a large part of our environment and are common in soil, decaying vegetable matter, animals and air. Despite this diversity the actual spectrum of fungal infections in man is limited and in neonates is limited even further. PMID- 8472103 TI - Malassezia furfur infection in a neonate. PMID- 8472104 TI - Anticoagulant-related intracranial haemorrhage. PMID- 8472105 TI - Application of SWOT analysis. AB - SWOT analysis is an effective and simple planning technique which addresses one aspect of many strategic planning processes. Given the complex nature of modern health care systems, the ability to use this type of technique can enable health professionals to participate more fully in the analysis and implementation of health care improvement. PMID- 8472106 TI - Decision making in surgery: operative management of a strangulated femoral hernia. AB - A strangulated femoral hernia can present significant problems to the surgeon, particularly since time may be at a premium. However, correct decision making can result in the safe management of this problem. This article describes the critical decisions central to a successful operation. PMID- 8472107 TI - Validation of rating scales in psychiatry. AB - Statistical analysis of psychiatric research requires the translation of qualitative data into quantitative form. This can be achieved using rating scales. However, the reliability and the validity, i.e. the validation of these scales, presents significant problems; these shall be outlined in this article. PMID- 8472108 TI - Morse marred by the gas man. PMID- 8472109 TI - Anxiety and endocrine responses to surgery. PMID- 8472110 TI - The use of carbon dioxide as an insufflation agent in barium enema--does it have a role? AB - A double blind prospective study was undertaken to evaluate the benefit of using carbon dioxide in double contrast barium enema (DCBE). 142 consecutive patients referred for DCBE were randomly allocated to receive either air or carbon dioxide (CO2) as the insufflation agent. The use of CO2 reduced the incidence of immediate and delayed severe pain from 31% to 12.5% and from 12.9% to 4.2% respectively. There was a statistically significant higher incidence of delayed severe pain in the younger age group as found in previous studies. Post evacuation films showed that there was less residual gas after CO2. The quality of the DCBE was unchanged. We urge the more widespread use of CO2 as insufflation agent in DCBE. PMID- 8472111 TI - Asymptomatic deep venous thrombosis in the calf: accuracy and limitations of ultrasonography as a screening test after total knee arthroplasty. AB - Patients who have recently undergone total knee arthroplasty are at high risk of developing deep venous thrombosis (DVT) in the calf. The clinical diagnosis of DVT is difficult in these patients owing to recent operation. A combination of compression ultrasonography (US) and colour flow imaging was used as a screening method of asymptomatic DVT in 51 patients who had undergone total knee replacement surgery. Both limbs were examined by US from the common femoral vein to the ankle approximately 7 days after operation and the results were compared with bilateral venography. 12 patients (24%) developed infrapopliteal DVT on the operated side, in two cases the thrombosis extended to the lower part of popliteal vein. One patient had bilateral thrombosis. US showed sensitivity of 77%, specificity of 96% and overall accuracy of 93%. US seems to be a useful screening method for DVT after knee replacement operation. PMID- 8472112 TI - Improved assessment of supraclavicular and abdominal metastases in oesophageal and gastro-oesophageal junction carcinoma with the combination of ultrasound and computed tomography. AB - The purpose of the study was to evaluate ultrasound and computed tomography in the assessment of distant metastases, supraclavicular and abdominal, in 113 patients with carcinoma of the oesophagus and gastrooesophageal junction. Ultrasound and computed tomographic findings were compared with the cytological data in 29 patients and with the surgical data in 84 patients. In assessing distant metastases, ultrasound and computed tomography had a sensitivity of 61% and 70%, and a specificity of 93% and 85%, respectively (p = 1.0). When ultrasound and computed tomography were combined the sensitivity increased to 83% and the specificity decreased to 81%. There was no significant difference in the assessment of supraclavicular metastases (p = 0.8), coeliac metastases (p = 1.0) or liver and other non-lymphatic abdominal metastases (p = 1.0) on ultrasound or computed tomography. The results show that both ultrasound and computed tomography should be used for assessment of distant metastases and abnormalities confirmed by image-guided biopsy. PMID- 8472113 TI - Quantitative image analysis of vertebral body architecture--improved diagnosis in osteoporosis based on high-resolution computed tomography. AB - 71 women, 64 post-menopausal, were examined by single-energy quantitative computed tomography (SEQCT) and by high-resolution computed tomography (HRCT) scans through the middle of lumbar vertebral bodies. Computer-assisted image analysis of the high-resolution images assessed trabecular morphometry of the vertebral spongiosa texture. Texture parameters differed in women with and without age-reduced bone density, and in the former group also in patients with and without vertebral fractures. Discriminating parameters were the total number, diameter and variance of trabecular and intertrabecular spaces as well as the trabecular surface (p < 0.05)). A texture index based on these statistically selected morphometric parameters identified a subgroup of patients suffering from fractures due to abnormal spongiosal architecture but with a bone mineral content not indicative for increased fracture risk. The combination of osteodensitometric and trabecular morphometry improves the diagnosis of osteoporosis and may contribute to the prediction of individual fracture risk. PMID- 8472114 TI - Rapid dynamic contrast-enhanced magnetic resonance imaging of the liver and portal vein. AB - The purpose of this study was firstly to show the diagnostic value of a rapid acquisition multislice sequence (TurboFLASH) during bolus injection of gadolinium DTPA by comparing it with the pulse sequences currently used for abdominal studies and secondly to develop improved scanning protocols for the liver. Patients were referred for upper abdominal studies including portal vein assessment. 40 patients were imaged in the coronal plane using a multislice TurboFLASH (TF) sequence (TR = 100; TE = 4) acquired during a breath-hold period of 19 s. The short echo time allows up to 11 slices of 5 mm thickness to be acquired simultaneously. Images were obtained before, during and after bolus administration of Gd-DTPA. The slices from each acquisition were combined using a maximum intensity projection algorithm to include all the vessels on a single image. Initially each patient was scanned using a conventional axial T2 weighted spin-echo sequence (T2W-SE) (TR2000; TE = 45/90) and a coronal T1 weighted spin echo sequence (TR450; TE = 15). The clarity of the demonstration of vascular anatomy was compared and scored for all sequences by two radiologists. Vessel patency, the conspicuity of mass lesions and the spread of tumour to adjacent structures were also scored. The anatomy of the main portal vein was significantly better shown by coronal TF images after bolus injection than on T2W SE images or TF before Gd-DTPA. The right and left portal veins were equally well shown by coronal TF with Gd-DTPA and T2W-SE images. There was no significant difference between contrast enhanced TF and T2W-SE imaging in visualization of the hepatic veins. More lesions were demonstrated by post-contrast TF than by T2W SE imaging. Portal venous occlusion was better appreciated by post-contrast TF. Our results demonstrate that Gd-DTPA TF imaging improves visualization of the main portal vein compared with SE sequences and provides a more accurate assessment of vessel patency. The segmental anatomy of the liver is better appreciated and the demonstration of focal liver lesions compared with T2W-SE images is improved during the non-equilibrium phase of enhancement. TF acquisitions before and after Gd-DTPA are obtained in approximately 5 min; thus a marked reduction in examination time can be achieved. PMID- 8472116 TI - Implementation of a programme for reduction of radiographic doses and results achieved through increases in tube potential. AB - Experiences in implementation of a programme to reduce doses to patients from radiographic examinations are described. A preliminary survey of entrance doses for selected examinations, calculated from mean exposure factors, identified equipment and examinations requiring attention. Subsequently more detailed studies were carried out with thermoluminescent dosimeters (TLDs). Results were coordinated with the aid of a database, which was used to monitor the agreement between dose calculations and TLD measurements. Surveys highlighted that doses from lumbar and thoracic spine examinations were high throughout the region. Reductions of 26-36% in entrance dose and 20-25% in effective dose were achieved by raising tube potentials for these examinations. This gave a reduction in annual collective dose of 4 man-Sv with no cost implication. In some departments dose charts were used to support the purchase of new screens. Surveys revealed a wide range in other factors such as transmission of X-ray table tops and results are being used in planning replacement of equipment. PMID- 8472115 TI - CT-dacryocystography for nasolacrimal duct obstruction following paranasal sinus surgery. AB - Nasolacrimal duct obstruction and consequent epiphora is a complication that may develop in some patients following paranasal sinus surgery. We describe the technique of CT-dacryocystography which entails contrast injection of the lacrimal system and simultaneous computed tomography (CT) scanning of the facial structures. This technique provides concurrent information regarding obstruction of the nasolacrimal duct and the presence of disease recurrence or persistence in the adjacent paranasal sinuses. The role of CT-dacryocystography prior to endoscopic dacryocystorhinostomy is discussed briefly. PMID- 8472117 TI - The dose-fractionation sensitivity of the kidney; assessment of viable tubule cross-sections at 19 months after X irradiation. AB - The formation of viable tubule cross-sections was assessed in histological sections of murine kidneys at 19 months after fractionated bilateral X-ray doses with 12 h intervals between fractions. The data were analysed using the linear quadratic model which provides values of alpha and beta characterizing the slope of the dose-response curve, and the ratio of alpha and beta indicative of the sparing effect of dose fractionation. The tubule data were characterized by alpha = 0.057 +/- 0.009 Gy-1, beta = 0.011 +/- 0.001 Gy-2, alpha/beta = 5.0 +/- 0.9 Gy. Also, the number of cells (per focus region of the nephron) calculated as being capable of producing a viable focus was 2.5 +/- 0.5, which was confirmed using a separate two-dose approach (2.1 +/- 0.3). Together with other data, of the order of 1000 regenerative cells per nephron (10(4) total cells) can be deduced. The values of the fractionation sensitivity parameters are similar to values measured previously for cells taken from irradiated kidneys up to a year after irradiation and forming colonies in primary culture, and also similar to values assessed using various functional measures of kidney injury. PMID- 8472118 TI - Sensitivity of human squamous cell carcinoma of the larynx to fractionated radiotherapy. AB - Data obtained for the response of tumours from two multicentre clinical trials of the British Institute of Radiology have been combined and studied. Both trials involved patients with laryngopharyngeal carcinoma. There were 734 patients in the first trial, recruited between 1965 and 1975, and 611 patients in the second trial, recruited between 1975 and 1985. Observed survival and tumour-free rates for all patients are calculated. T-class and the nodal status of the patient at the start of the treatment were important factors in the determination of both observed survival and tumour-free rates. Overall treatment time was an important factor in determining the recurrence of tumour. The longer the overall treatment time the greater was the chance of tumour recurrence. The linear-quadratic (LQ) model was used in the analysis of the tumour recurrence data for a large group of patients with laryngeal tumours without nodal involvement. A small alpha/beta ratio of 0.94 Gy was obtained for T3 tumours while that of T2 tumours was negative, -10.5 Gy. The value for T1 tumours was higher at 23 Gy. However, use of the LQ model with a time component increased the alpha/beta ratios to 26.0 +/- 27.20 Gy, 18.0 +/- 12.33 Gy and 13.38 +/- 5.40 Gy for T1, T2 and T3 tumours, respectively. The time component, the gamma/alpha ratios, for these tumours were 0.15 +/- 0.27 Gy/day, 0.81 +/- 0.18 Gy/day and 0.76 +/- 0.15 Gy/day, respectively. PMID- 8472119 TI - Technical note: a new afterloading applicator for primary brachytherapy of endometrial cancer. PMID- 8472120 TI - Case report: allergic aspergillosis of the sphenoid sinus: pitfall on MRI. AB - Recent reports indicate that fungal sinusitis is more common than previously thought. Four different histological subtypes of Aspergillus sinusitis are now recognized. Fulminant Aspergillosis is usually seen in immunosuppressed patients, and chronic invasive Aspergillus sinusitis, allergic Aspergillus sinusitis and Aspergilloma are seen in the non-immunocompromised individual. We present a case of progressive unilateral visual loss in a 30-year-old woman. The unusual magnetic resonance findings and the value of computed tomography are discussed. PMID- 8472121 TI - Case report: fatal pulmonary Kaposi's sarcoma and Castleman's disease in a renal transplant recipient. AB - Two unusual complications of immunosuppression, Castleman's disease and Kaposi's sarcoma, occurring in a renal transplant recipient, are reported. Kaposi's sarcoma is a potentially curable condition in immunosuppressed patients if recognized and treated appropriately. In this patient, the pulmonary Kaposi's sarcoma was not diagnosed and this lead to the patient's death. PMID- 8472122 TI - Case report: multiple myeloma presenting as bilateral orbital masses: CT and MR appearances. PMID- 8472123 TI - Case report: haemothorax in hereditary multiple exostosis. PMID- 8472124 TI - Case report: cyclosporin A-induced neurotoxicity. AB - Acute encephalopathy is a recognized toxic effect of Cyclosporin A (CsA) in organ transplantation recipients. A 16-year-old girl presented with acute encephalopathy 2 weeks after CsA and methylprednisolone medication for idiopathic uveitis. Magnetic resonance imaging showed cortical and white matter occipital changes, which were not visible 2 months later. With expanding indication for CsA use, an increasing number of neurotoxic cases are to be expected. PMID- 8472125 TI - Case of the month: an unexpected twist. PMID- 8472126 TI - Short communication: spinal bone density measured with a 5 s scan. PMID- 8472127 TI - Basal cell carcinomas do metastasize. PMID- 8472128 TI - The role of hysterosalpingography in modern gynaecological practice. PMID- 8472129 TI - The role of hysterosalpingography in modern gynaecological practice. PMID- 8472130 TI - Hepatectomy for liver metastases. PMID- 8472131 TI - Perspectives in European surgery. PMID- 8472132 TI - Emergency laparoscopic surgery. AB - The acute abdomen continues to demand a large proportion of the general surgeon's workload. Recent studies have demonstrated that management errors can be significantly reduced using selective laparoscopy and this should now become routine practice. The continuing advances in laparoscopic surgery that permit many emergency procedures to be performed by this route provide increased impetus for a combined approach using diagnostic and therapeutic laparoscopy for the management of the acute abdomen. Results of current studies must be awaited before the exact role of emergency laparoscopic surgery can be defined, but early reports suggest several advantages in using laparoscopy to manage conditions such as acute appendicitis, perforated peptic ulcer and gynaecological emergencies. PMID- 8472133 TI - Elective lymph node dissection in the management of malignant melanoma. AB - The surgical management of regional nodes in patients with cancer has been controversial for many years. This paper reviews the role of elective lymph node dissection in the management of malignant melanoma. The evidence for and against elective lymphadenectomy is discussed and a policy of therapeutic, rather than elective, lymph node excision recommended. PMID- 8472134 TI - Cytokines, sepsis and immunomodulation. AB - Tissue injury and infection produce significant alterations in host metabolic and immune homeostasis. It is increasingly clear that many of these changes result from a complex cascade of mononuclear phagocyte-derived endogenous mediators. Among the more important is a group of host proteins called cytokines, which play an integral role in mediating the host response to tissue injury and infection. Of these proteins, tumour necrosis factor (TNF) and interleukin (IL) types 1 and 6 have received much attention for their pathophysiological roles in infection and trauma. Evidence is reviewed for the involvement of these cytokines in the characteristic alterations in the metabolic and immune responses to such injury. These endogenous mediators initiate an integrated fuel substrate and hormonal adjustment to trauma and sepsis, and help to provide optimal metabolic homeostasis for systemic host defences. Widespread tissue injury, especially when associated with fulminant sepsis, may, however, precipitate massive release of TNF, IL-1 and IL-6, triggering a series of reactions involving multiple organs, and culminating in the 'sepsis syndrome'. New therapies designed to downregulate this aberrant response, either by neutralizing endotoxin directly or by blocking the release or actions of these cytokines, are reviewed. Although these treatments hold much promise for the future management of severely traumatized and infected patients, careful evaluation of both the benefits and complications of therapy is needed before widespread clinical use can be recommended. PMID- 8472135 TI - Intra-abdominal photodynamic therapy: from theory to feasibility. AB - Photodynamic therapy is a new anticancer technique, directed at the selective destruction of neoplastic tissue, which has been used in the treatment of superficial or intraluminal lesions. The technique has now reached the stage where it can be considered in the peroperative management of gastrointestinal tumours, for example in an attempt to eradicate micrometastases in the tissue around the primary tumour or in residual lymph nodes after curative resection. Many practical problems remain to be solved, such as the pharmacokinetics of photosensitizers, the dosimetry of illumination and the sensitivity of intra abdominal organs. An experimental and clinical evaluation is in progress to assess the feasibility of photodynamic therapy in surgical practice. PMID- 8472136 TI - High incidence of arteriovenous fistula after biopsy of kidney allografts. AB - Arteriovenous fistula (AVF) is a well known but rarely diagnosed complication of percutaneous biopsy of kidney allografts. In the past diagnosis was usually made when clinical signs of an AVF occurred but Doppler ultrasonography has now enabled non-invasive diagnosis. Doppler examination of kidney allografts was performed after 100 biopsies. A total of ten AVFs were diagnosed within 2 weeks of biopsy. On repeated examination 2 months later, no additional fistula was detected. All fistulas were detected by abnormal colour shading of the artery and vein of the fistula caused by high blood velocity. Quantification in the artery supplying the fistula showed a higher systolic velocity compared with that in a normal artery of comparable size and location in the graft (mean (range) 64 (25 150) versus 36 (20-65) cm/s, P < 0.05). Diastolic velocity was also higher in the artery supplying the fistula than in a normal artery (mean (range) 34 (9-72) versus 7 (0-13) cm/s, P < 0.05). In the group with an AVF the proportion with a prolonged bleeding time (> 3 min) was higher (80 versus 47 per cent, P < 0.05), as was the prevalence of a platelet count < 200 x 10(9)/l (60 versus 22 per cent, P < 0.05). After detection of the fistula, four of the grafts were lost because of rejection and two patients died from sepsis during antirejection treatment. During follow-up of the remaining four AVFs, three disappeared spontaneously and one persisted. None of the fistulas has had an impact on renal function requiring intervention. In conclusion, AVF is a complication observed frequently after kidney allograft biopsy that can be detected and monitored by Doppler ultrasonography. PMID- 8472137 TI - Autologous predonation, haemodilution and intraoperative blood salvage in elective abdominal aortic aneurysm repair. AB - The feasibility of predonated autologous blood transfusion and intraoperative blood salvage in elective abdominal aortic aneurysm repair was studied. Twenty consecutive patients were evaluated, of whom five were excluded according to protocol criteria. Patients each donated 1 unit blood 14 and 7 days before operation. A third unit was withdrawn in the anaesthetic room and replaced with Hartmann's solution, producing a haemodiluted state. Intraoperative losses were minimized using the Haemonetics Cell Saver III Plus autotransfusion system. Predonated blood from two patients passed its expiry date owing to repeated operation postponements, leaving 13 patients for study. The mean(s.d.) intraoperative blood loss was 700(300) ml with a mean(s.d.) intraoperative salvage of 420(300) ml. Two patients were transfused intraoperative salvage of 420(300) ml. Two patients were transfused according to clinical need. Thus nine patients safely avoided homologous transfusion. With autologous predonation, haemodilution and intraoperative blood salvage, elective aortic aneurysm repair can be performed safely with minimal need for homologous blood. PMID- 8472138 TI - Surgical treatment of reflux stricture of the oesophagus. AB - The choice of surgery in patients with reflux-induced oesophageal stricture remains controversial. From 1976 to 1990, a total of 65 patients underwent fundoplication (36 patients), Collis gastroplasty plus fundoplication (ten), total duodenal diversion (four) and oesophageal resection (15). The postoperative mortality rate was 5 per cent (three patients): necrosis of the colon transplant in two patients and acute pancreatitis in one. The median follow-up was 25 (range 6-120) months. After conservative surgery, the median number of dilatations per patient per year significantly decreased (P < 0.001). Nine patients (25 per cent) complained of persistent or recurrent symptoms after standard fundoplication and six required reoperation. Clinical results were satisfactory in patients who underwent Collis fundoplication, total duodenal diversion and oesophageal resection. It is concluded that the causes of failed fundoplication are irreversible stricture or persistent gastro-oesophageal reflux; the latter may be caused by inefficacy or deterioration of the partial fundoplication wrap. A subtle degree of oesophageal shortening is probably underestimated in such patients and this may explain the better results obtained with the Collis fundoplication. Total duodenal diversion is a good therapeutic option in patients who have undergone previous oesophagogastric surgery. Oesophageal resection should be reserved for patients with tight strictures unresponsive to dilatation or those with scleroderma, multiple previous operations or severe dysplasia in Barrett's oesophagus. PMID- 8472139 TI - Thoracoscopy in oesophagectomy for oesophageal cancer. PMID- 8472140 TI - Monofilament versus multifilament absorbable sutures for abdominal closure. AB - This study compares monofilament continuous absorbable sutures with multifilament interrupted absorbable sutures for abdominal closure. Before closure of an abdominal incision, 988 patients were randomized to receive either a monofilament polyglyconate (Maxon) or a multifilament polyglactin 910 (Vicryl) suture. At 1 year after operation, 684 patients (69 per cent) were examined for the presence of incisional hernia, sinus and other wound-healing problems; 179 (18 per cent) had died and 125 (13 per cent) did not attend for follow-up. Incisional hernia occurred in 8 per cent of patients receiving monofilament continuous sutures compared with 6 per cent of those having multifilament interrupted closure (P not significant). Wound dehiscence occurred in 1 per cent of both groups. The mean time for suturing was 7.1 min for monofilament continuous and 8.7 min for multifilament interrupted sutures (P < 0.001). It is concluded that closure of an abdominal incision can be effected by a monofilament continuous absorbable suture more quickly than by multifilament interrupted absorbable sutures without an increased risk of wound dehiscence or incisional hernia. PMID- 8472141 TI - Early gastric cancer: follow-up after gastrectomy in 159 patients. AB - The postoperative course of 159 patients with early gastric cancer operated on between 1974 and 1987 was followed for a median of 7.3 years. The cumulative 10 year survival rate(s.e.) calculated using follow-up data to the end of 1989 was 90.6(2.7) per cent excluding operative death and that from causes other than gastric cancer, or 86.3(3.0) per cent when operative mortality was included. The overall 10-year survival rate(s.e.) was 77.3(3.7) per cent. Univariate analysis showed a significant difference in survival rates between cancers confined to the mucosa and those with submucosal invasion (P = 0.02), between patients with and without lymph node metastases (P = 0.05) and between those < or = 50 and > 50 years of age (P = 0.02). Using Cox multivariate analysis and a stepwise procedure for eight variables (sex, age, depth of invasion, lymph node metastases, presence of ulceration, location, histological type, type of surgery), age and histological type had the most significant effect on survival. Seven operative deaths were recorded. Eleven patients died from recurrent cancer and one is still alive with a gastric remnant recurrence. Other causes of death were metachronous primary cancer (six patients), cardiovascular disease (two), pneumonia (three), sepsis (one) and car accident (one). Although the prognosis of early gastric cancer is relatively good in western countries, patients should be carefully followed over a long period for late recurrence and for metachronous cancer, which has a high incidence. PMID- 8472142 TI - Gastrointestinal surgery in the aged. PMID- 8472143 TI - Splenectomy in human immunodeficiency virus-related thrombocytopenia. AB - To evaluate the efficacy and safety of splenectomy in patients with human immunodeficiency virus (HIV)-related thrombocytopenia, 30 HIV-infected patients with thrombocytopenia (platelet count < 50 x 10(9)/l) who underwent splenectomy were followed prospectively for a mean period of 42 months. There were no perioperative deaths and morbidity was minimal. Twenty-one patients had a persistent complete response, six had a partial response and were asymptomatic after splenectomy, and only three showed no response. Three patients developed acquired immune deficiency syndrome during follow-up, an incidence that was no different from that expected. Splenectomy is a safe and effective treatment in HIV-infected patients with severe symptomatic thrombocytopenic purpura resistant to medical therapy. PMID- 8472144 TI - Splenectomy for splenomegaly exceeding 1000 grams: analysis of 47 patients. AB - Forty-seven patients who underwent splenectomy for splenomegaly > or = 1000 g were studied retrospectively. There were 29 men and 18 women of mean age 56 (range 19-87) years. Haematological malignancy was the most common disorder (42 patients). The main indications for splenectomy were cytopenia (20 patients), diagnosis (14), initial treatment of leukaemia (eight), pain (four) and spontaneous rupture (one). Thirteen patients underwent an associated surgical procedure. One patient died (mortality rate 2 per cent) and 12 (26 per cent) had postoperative complications. The advantages of splenectomy included histopathological diagnosis in 13 of 14 patients with splenomegaly of unknown origin, effective initial treatment in prolymphocytic and hairy cell leukaemia, definitive relief of pain in all affected patients, and long-term improvement of cytopenia in most. PMID- 8472145 TI - Percutaneous ultrasound-guided drainage of intra-abdominal abscesses. AB - A retrospective review of 200 patients with intra-abdominal abscesses treated by percutaneous ultrasound-guided drainage is reported. Abscesses were simple in 151 patients (75.5 per cent) and complex in 49 (24.5 per cent). In 12 patients the abscess communicated with the gastrointestinal tract. There were 17 critically ill patients for whom percutaneous drainage was the only therapeutic option possible. The success rate was 94.7 per cent (143 of 151 patients) for simple abscess and 69 per cent (34 of 49) for complex abscess. The overall success rate was 88.5 per cent. The mortality rate was 1.3 per cent (two patients) for simple and 16 per cent (eight patients) for complex abscess. The overall mortality rate was 5.0 per cent. Percutaneous ultrasound-guided drainage should be the initial drainage procedure in patients with a simple abdominal abscess. The presence of a complex abscess should not prevent an attempt at percutaneous catheter drainage, particularly in high-risk patients, although the risk of failure is greater in such cases. PMID- 8472146 TI - Repeat liver resection for recurrent colorectal metastases. AB - Sixteen patients underwent 18 repeat liver resections for recurrence of colorectal hepatic metastases that had been previously resected. Only minor liver resection had been undertaken at the first operation; three were palliative. The second operation was major hepatectomy in ten patients, minor resection in five and orthotopic liver transplantation in one. In one patient, lung metastases were resected before the second operation. One repeat hepatectomy was palliative. After partial liver resection, there were no deaths and complications were observed in six of 15 patients. One patient died 2 weeks after liver transplantation. After the second resection, 2-, 3- and 5-year survival rates were 67, 57 and 30 per cent; the mean survival time was 33 (range 8-93) months. Tumour recurrence was observed in 11 of 14 patients 4-32 (mean 13) months after a second curative liver resection; two patients received a third curative operation for recurrent liver metastases. After the second curative hepatectomy, seven patients died from disease after a mean of 36 (range 14-61) months and seven are currently alive at a mean of 33 (range 8-93) months. Four of these patients are free from disease 26-93 months after resection and three are alive with recurrence. Repeat hepatectomy for recurrent colorectal metastases can prolong survival in selected patients and has low operative risk. PMID- 8472147 TI - Ultrasonography in the diagnosis of gallbladder polyps. PMID- 8472148 TI - Impact of laparoscopic cholecystectomy in the UK: a survey of consultants. PMID- 8472149 TI - Lipomatous polyposis of the colon. PMID- 8472150 TI - Photoplethysmography in the diagnosis of superficial venous valvular incompetence. AB - Photoplethysmography was compared with clinical investigation combined with Doppler ultrasonography in the diagnosis of superficial venous valvular incompetence of the lower limb. In 268 consecutive patients, 536 limbs were investigated. A total of 22.1 per cent of the photoplethysmographic investigations were uninterpretable because they did not allow reliable determination of the refilling time. Agreement between clinical investigation combined with Doppler ultrasonography and photoplethysmography was found to be poor (kappa = 0.30). These results suggest that photoplethysmography is not the non-invasive method of choice for routine evaluation of superficial venous valvular incompetence of the leg. PMID- 8472151 TI - Cardiac risk and peripheral vascular surgery: new approach based on a multifactorial risk index. AB - An inexpensive approach to stratification of patients admitted for arterial surgery into groups of high and low cardiac risk has been prospectively evaluated in 235 consecutive patients. The Goldman and Detsky indices, assessed by a nurse the day before surgery, both identified patient groups with increased risk of lethal or potentially lethal (myocardial infarction, pulmonary oedema) cardiac events within 30 days after peripheral vascular surgery. The Goldman index was the more sensitive predictor of cardiac death (overall frequency 3.1 per cent) while the Detsky index was superior for prediction of non-lethal cardiac events (overall frequency 5.9 per cent). The simplest and yet most effective stratification into high and low cardiac risk was achieved using a Detsky score of 10 as the cut-off. It is concluded that multifactorial risk index-based preoperative screening can identify low-risk patients (Detsky score < or = 10), who may be accepted for vascular surgery (aortic aneurysm surgery excluded) without additional cardiac testing. PMID- 8472152 TI - Effect of seeding time and density on endothelial cell attachment to damaged vascular surfaces. AB - An in vitro model to facilitate the study of endothelial cell seeding of damaged vascular surfaces has been developed. This may have applications in the study of endothelial seeding of angioplasty and endarterectomy sites. Using this model, the optimum endothelial seeding time for attachment to damaged vascular surfaces should not exceed 30 min and, to achieve confluent cell attachment, a seeding density > 5 x 10(5) cells/cm2 should be used. PMID- 8472153 TI - Long-term results of treatment of peptic stricture of the oesophagus with the Angelchik prosthesis. AB - An Angelchik prosthesis was inserted in 43 patients with a peptic stricture above a hiatus hernia; 16 showed columnar lining of the oesophagus below the stricture. The mean preoperative bore of strictures was 8.7 mm. Within months, and without dilatation, 33 strictures shortened, 35 widened and of these 13 disappeared with a mean bore of 11.7 mm. In the long term, three more strictures resolved but three recurred. Final measurements gave a mean bore of 12.2 mm. The mean follow up was 3.5 years. Symptomatic and radiological assessments suggested that the prosthesis was less effective when sited in the chest. PMID- 8472154 TI - Oesophagectomy by a transhiatal approach or thoracotomy: a prospective randomized trial. AB - A prospective randomized trial of 67 patients undergoing oesophagectomy by either a transhiatal approach or right-sided thoracotomy was conducted over a 40-month period. In 32 patients the approach was transhiatal and 35 had a thoracotomy; the groups were well matched before operation. There were two hospital deaths in patients having the transhiatal oesophagectomy and three in those undergoing thoracotomy. Blood transfusion, intensive care stay and overall time of hospitalization were not significantly different between the two groups. There was no difference in the postoperative morbidity rate and, in particular, the incidences of pulmonary complications were similar (19 per cent for transhiatal oesophagectomy, 20 per cent for thoracotomy) with anastomotic fistula in 6 and 9 per cent respectively. The median (range) operating time was significantly longer in patients having thoracotomy (6 (3.5-9.5) versus 4 (3-8) h). Long-term survival was unaffected by the type of operation performed or addition of preoperative chemotherapy or radiotherapy. Nodal status was a significant prognostic factor within but not between the two groups. It is concluded that oesophagectomy by a transhiatal route or right thoracotomy are equally effective surgical options for treatment of squamous cell oesophageal cancer. PMID- 8472155 TI - Intragastric bile acid and symptoms in patients with an intrathoracic stomach after oesophagectomy. AB - Bile acid concentration and symptoms were evaluated in 24 patients after total oesophagectomy and gastric pull-up. Patients were randomly allocated to receive pyloroplasty or not. After operation all were followed for a minimum of 6 months. Bile acid concentration in the gastric juice was estimated. The mean(s.d.) bile acid concentration 6 months after surgery was similar in patients with and without pyloroplasty (34.9(30.1) and 25.0(24.2) mg/dl respectively). Postprandial discomfort and bilious eructations were the two most commonly observed symptoms in both groups. Other features noted were vomiting, anaemia and anorexia. These did not however seem to be related to intragastric bile acid concentration of individual patients in either group and occurred irrespective of whether pyloroplasty was performed or not. PMID- 8472156 TI - Laparoscopic resection of a bleeding gastric tumour. PMID- 8472157 TI - Increasing incidence of carcinoma of the gastric cardia in Sweden from 1970 to 1985. AB - Several American, Japanese and European centres have reported an increase in carcinoma of the gastric cardia, contrary to the general trend in the incidence of gastric cancer. The aim of this nationwide population-based study was to describe trends in the incidence of tumours of the gastric cardia in Sweden over the 16-year period from 1970 to 1985. The Swedish cancer register, which is more than 95 per cent complete, was used to identify cases. There were 1514 men and 481 women with cancer of the gastric cardia. The age-standardized rates increased in men from 1.9 per 10(5) population in 1970-1973 to 3.0 per 10(5) in 1982-1985, corresponding to a mean annual increase of 2.5 per cent (95 per cent confidence interval (c.i.) 1.6-3.4 per cent). In women, the age-standardized rates increased from 0.5 per 10(5) in 1970-1973 to 0.8 per 10(5) in 1982-1985, the mean annual increase being 0.9 per cent (95 per cent c.i. 0.0-1.8 per cent). The highest incidences were found in southern Sweden, contrary to the geographical distribution of gastric cancer in general, which shows a south-to-north gradient. The disparate epidemiological features of cancer of the cardia and gastric cancer at other sites suggest that the aetiologies may also be different. Since little is known about the aetiology of cancer of the cardia, and the incidence seems to be rising rapidly, analytical studies are urgently needed. PMID- 8472158 TI - Gastric cancer and Helicobacter pylori infection. AB - Gastric adenocarcinoma can be divided into two histopathological types: intestinal and diffuse. In addition to the role of environmental factors, an association between gastric cancer and Helicobacter pylori has been suggested. A retrospective study was therefore carried out among 46 patients who had gastric cancer. As a control group, 40 patients with non-malignant disorders were selected (11 patients with peptic ulcer, 12 with chronic superficial gastritis, 17 with chronic atrophic gastritis). Twenty-six cancers were classified as intestinal type and 20 as diffuse type. H. pylori was found in 23 (88 per cent) of the intestinal type and 11 (55 per cent) of the diffuse type (P < 0.05). Patients with the intestinal-type gastric cancer had a higher prevalence of H. pylori infection than those with gastric ulcer (55 per cent) and chronic superficial gastritis (50 per cent) (P < 0.05). These findings suggest that there is a possible association between the intestinal type of gastric cancer and H. pylori infection. PMID- 8472159 TI - Resection of presumed benign liver tumours. AB - The surgical treatment of benign liver tumours (focal nodular hyperplasia (FNH) and hepatic adenoma) remains controversial. From 1984 to 1990, all 51 women aged below 50 years who presented with presumed benign liver tumours and without chronic liver disease underwent tumour resection. Preoperative assessment included liver tests, ultrasonography and dynamic computed tomography in all patients, plus angiography (n = 20), magnetic resonance imaging (n = 22) and technetium-sulphur colloid liver scintigraphy (n = 19). The aims of this study were to compare preoperative and final pathological diagnosis and determine whether surgical treatment was justified. Preoperative assessment suggested FNH in 18 patients and hepatic adenoma in 11. In 22 patients, the distinction between FNH and adenoma could not be determined before operation. Operative procedures included resection of one segment or less in 22 patients, two segments in 14 and three or more segments in 15. There was no postoperative death and no serious complication. The final diagnosis after pathological examination of resected specimens was FNH in 36 patients (71 per cent), including the 18 presumed before operation to have FNH, hepatic adenoma in 12 (24 per cent) and malignant lesions in three (6 per cent): hepatocellular carcinoma (HCC) arising in normal liver, fibrolamellar carcinoma, and adenoma containing areas of HCC in one patient each. IN CONCLUSION: (1) precise preoperative diagnosis of benign liver tumours remains difficult despite new imaging methods; (2) malignant liver tumours can go unrecognized; and (3) resection of all these lesions can be carried out safely. Resection of presumed benign liver tumours should be performed in young women when a preoperative diagnosis of FNH is not firmly established. PMID- 8472160 TI - Clinical trial of tamoxifen in patients with irresectable pancreatic adenocarcinoma. The Yorkshire Gastrointestinal Tumour Group. AB - Oestrogen-binding sites are present in tissue samples of adenocarcinoma of the pancreas. Uncontrolled studies have suggested that survival of patients with this tumour may be extended by using the antioestrogen drug tamoxifen. Forty-four patients with biopsy-proven irresectable adenocarcinoma of the pancreas were recruited into a randomized placebo-controlled clinical trial of tamoxifen 20 mg twice daily. All patients were assessed at the time of diagnosis and at monthly intervals using the Karnofsky and the Hospital Anxiety and Depression scores for quality of life. Analysis of survival by life-tables and the log rank test revealed no significant difference in the duration of survival of patients treated with tamoxifen or placebo. Quality-of-life assessment revealed no significant difference between the groups. Tamoxifen does not confer significant benefit to patients with irresectable pancreatic cancer. PMID- 8472161 TI - Suppression of macrophage function by suture materials and anastomotic recurrence of Crohn's disease. AB - After surgical excision of bowel, Crohn's disease is likely to recur around the anastomosis. It is suggested that this may indicate a biological effect of suture materials on gastrointestinal immunology. To investigate this, the influence of six suture materials on the function of macrophages obtained from the rat peritoneal cavity and human intestinal mucosa was assessed. All materials significantly impaired macrophage function. PMID- 8472162 TI - Sphincter rupture in childbirth. AB - Thirty-eight women with rupture of the anal sphincter occurring during childbirth were followed for 3-12 months. Nineteen had complete rupture of the external anal sphincter, 14 had a lesion involving more than half of the sphincter muscle and five had a superficial rupture. Fourteen patients presented with continence disturbances: nine to solid or liquid faeces and five to flatus. Incontinence was present in nine women 3 months after childbirth. Anal manometry and electromyography were performed in patients 3-5 days after delivery and repeated at 3, 6 and 12 months. Manometry and electromyography were also performed in 16 control subjects who were nulliparous or had given birth more than 2 years previously and 24 primiparous controls, who were investigated at 3-5 days and at 3 months. There were significant differences between both incontinent and continent patients compared with nulliparous and primiparous controls. Primiparous control subjects had decreased anal squeeze pressure as well as decreased electromyographic activity on the first days after delivery compared with nulliparous controls. After 3 months no differences were found. Continence disturbances are frequent after sphincter rupture; these patients should be monitored after delivery and those with persisting incontinence offered sphincter repair. PMID- 8472163 TI - Diaphragm-like strictures of the colon induced by non-steroidal anti-inflammatory drugs. PMID- 8472164 TI - Subtotal splenectomy in Gaucher's disease: towards a definition of critical splenic mass. PMID- 8472165 TI - Iliofemoral versus femorofemoral bypass: a 6-year audit. PMID- 8472166 TI - Perineal trauma from cassette tape boxes. PMID- 8472167 TI - Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. PMID- 8472168 TI - Reperfusion injury in skeletal muscle: a prospective study in patients with acute limb ischaemia and claudicants treated by revascularization. PMID- 8472169 TI - Physiological and metabolic responses to open and laparoscopic cholecystectomy. PMID- 8472170 TI - Place of routine operative cholangiography at cholecystectomy. PMID- 8472171 TI - Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia. PMID- 8472172 TI - Third European Conference on Child Abuse and Neglect, Prague, Czechoslovakia. June 23-26, 1991. PMID- 8472173 TI - A profile of violence toward children: a national study. AB - This paper presents a profile of violence toward children in the United States, based on the results from the Second National Family Violence Survey. A national probability sample of 6,002 households was surveyed by telephone in 1985, of which 3,232 households had at least one child under 18 years old living at home. Minor violence, or physical punishment, was most common among mothers, caretakers 18 to 37 years old, fathers who were unemployed, caretakers with blue-collar occupations, households with two to four children at home, and among caretakers who used alcohol and other drugs, male children, and children 3 to 6 years old. The highest rates of abusive violence occurred in families located in the East, families whose annual income was below the poverty line, families where the father was unemployed, families where the caretakers held blue-collar jobs, families with four or more children, caretakers who used drugs at least once, male children, and children 3 to 6 years old. Logistic regressions were done to examine the predictive value of these variables. PMID- 8472174 TI - Intensive Family Preservation Services with abused and neglected children: an examination of group differences. AB - Intensive Family Preservation Services (IFPS) have emerged as one of the most widely-employed placement prevention models in the field of Family-Based Services. Most IFPS evaluations have reported positive outcomes, but some results have been mixed. The use of heterogeneous client samples may explain some of the equivocal findings, so a study was designed to assess maltreatment group differences in a relatively large sample of families referred by Child Protective Service (CPS) agencies. It was found that: (a) Neglectful families, in contrast to abusive ones, were poorer, more reliant on public income, more likely to be headed by a single parent, had more children at imminent risk of placement, and were more likely to have medical, mental health, and substance abuse problems; (b) families referred for both abuse and neglect were more similar to the neglect only group than the abuse-only one; and (c) although the majority of all children avoided placement, children from neglectful families were almost twice as likely to be placed than children from abusive ones, with those from multiple maltreatment families being at highest risk. The implications for research methodology and service delivery are discussed. PMID- 8472175 TI - Self-report of Guardians Ad Litem: provision of information to judges in child abuse and neglect cases. AB - Reporting patterns of Guardians Ad Litem to judges in cases on child abuse and neglect were studied. Guardians indicated which information they had included in reports to judges in recently adjudicated cases of child abuse and neglect. Information reported in child abuse cases was compared with information reported in neglect cases, and the pattern of reporting was found to be the same in both types of cases. Guardians most frequently included information concerning the child's physical safety, the interaction between the parent(s) and the child, and personality characteristics of the parent(s). Less frequently reported was information regarding conflict in the home and family enmeshment. PMID- 8472176 TI - Morbidity and death due to child abuse in New Zealand. AB - The purpose of this study was to explore under-diagnosis and racial bias among child abuse morbidity and mortality data from New Zealand. Computerized files of all intentional injury fatalities among children 16 years of age and under for 1978-87, and all hospital discharges for intentionally injured children 16 and under for 1988, were analyzed for evidence of physical abuse and sexual abuse. Among the 92 fatalities, only 21 of 68 deaths due to physical and/or sexual abuse were so coded. In both the mortality and the morbidity data, there was an association between the diagnosis of child abuse and race. In the case of fatalities, Maori and Samoan abuse victims were more likely to be assigned an E code of E967 ("child battering and other maltreatment") than were "others" (p = 0.04), controlling for sex. In the case of hospitalizations, the association between E967 and whether or not the victim was European was significant for physical abuse only (p = 0.05). Assignment of N-code = 995.5 ("child maltreatment syndrome") as the reason for admission was significantly associated with race for those cases considered by us to have been abused, controlling for age (p = 0.002) or sex (p = 0.004). PMID- 8472177 TI - Child provocativeness and gender as factors contributing to the blaming of victims of physical child abuse. AB - This study was an investigation of factors contributing to blame attributions directed toward victims of physical child abuse. The total sample consisted of 897 college undergraduates. Subjects read eight vignettes describing physically abusive parent-child interactions, and indicated their attributions of responsibility toward parent and child. We predicted that: (a) aggressively provocative children (compared to nonprovocative) would be ascribed greater blame; (b) male subjects would be more likely to blame the child; (c) in situations in which the abusive parent is male (compared to female), the child would be blamed more; and (d) male children (compared to females) would receive greater blame. The results supported all hypotheses. The data also suggested several interaction effects. Significance tests were supplemented with effect size analyses. PMID- 8472178 TI - Mother-son sexual abuse: rare or underreported? A critique of the research. AB - This paper reviews the literature regarding mother-son sexual abuse and critiques the methodologies that may be responsible for the underreporting of such cases. The review of the clinical and empirical literature reveals discrepancies regarding estimates of incidence and prevalence of mother-son sexual abuse. The author suggests improved methodologies for researchers interested in studying this topic. PMID- 8472179 TI - The psychological evaluation of child sexual abuse using the Louisville Behavior Checklist and Human Figure Drawing. AB - Accurately detecting victims of child sexual abuse when physical evidence is lacking is a problem frequently faced by clinicians. This study investigated whether Human Figure Drawings and the Louisville Behavior Checklist could be used to accurately identify sexually abused children, mental health clinic-referred children, and community children. Discriminant function analysis indicated that the groups differed significantly on the measures. There was some misclassification of individual children on the basis of their checklist and drawing scores. Results suggested limited support for the Louisville Behavior Checklist but caution in using Human Figure Drawings in the assessment of sexual abuse. PMID- 8472180 TI - Children's patterns of disclosures and recantations of sexual and ritualistic abuse allegations in psychotherapy. AB - Patterns of disclosures and recantations of abuse made in psychotherapy were examined in a sample of 63 children who reported sexual and ritualistic abuse in a preschool setting. Therapists completed a measure that instructed them to identify the time since the child began therapy when any disclosures or recantations were made, to specify the type of abuse disclosed or recanted, and to identify any events that might be related to the timing of a disclosure or recantation. The findings revealed that the majority of subjects (76.2%) disclosed abuse within the first month of therapy. Recantation occurred in 17 cases (27%) and all but two children who recanted redisclosed abuse after the initial recantation. There was some evidence that children's experiences within the legal system may have been associated with recantations. Subjects tended to make vague disclosures before revealing more specific acts, reveal less intrusive sexual abuse (e.g., kissing) before more intrusive types (e.g., intercourse), and to disclose ritualistic abuse after other types. PMID- 8472181 TI - HIV vulnerability and the adult survivor of childhood sexual abuse. AB - The purpose of this article is to sensitize clinicians working in the field of childhood physical/sexual abuse to the connection between untreated childhood traumatization and HIV high-risk behaviors. The characteristic abuse symptoms of chronic depression, sexual compulsivity, revictimization, and substance abuse are identified as barriers to HIV education and intervention for survivors. An overview of the existing HIV/child abuse connection research, an illustrative case history and a discussion regarding the clinical implications of these connections are offered. PMID- 8472182 TI - A brief group treatment for the modification of denial in child sexual abusers: outcome and follow-up. AB - We investigated whether brief structured group treatment could produce a reduction of denial of sexual offenses in males convicted of sexually offending against children. Such denial can additionally harm victims and often precludes admission into sex offender treatment programs, thus ruling out an opportunity to decrease the potential of reoffending. The group treatment contained elements of victim empathy, cognitive restructuring, sex education, assertiveness and social skills, education about sex offender therapy, and a discussion of the possible consequences of continued denial. Seventeen child sexual offenders in denial were run in two groups. Despite an average length of denial of nearly two years, by post-treatment the majority of offenders had come out of denial. Moreover, follow up denial data indicated continued admission, and above-average compliance with subsequent sex offender therapy. Although the lack of an experimental design precludes causal inference, these results are suggestive of an effective method for modifying denial in sex offenders against children. PMID- 8472183 TI - The relationship between childhood sexual abuse and subsequent onset of bulimia nervosa. AB - Seventy-two young adult women identified by the Bulimic Investigatory Test, Edinburgh (BITE) as having a high probability of suffering from bulimia nervosa were compared with 72 matched controls who did not display bulimic symptoms. Both groups were given measures of sexual abuse history, dissociation, and early family mealtime experiences. Rates of self-reported sexual abuse after the age of 12 with an adult relative as the perpetrator were significantly greater in the women diagnosed as bulimic. Nonsignificant but high rates of sexual abuse prior to age 12 were also found for this group. Dissociative experiences were also significantly more common in the bulimic group overall, and higher still for bulimic women who reported sexual abuse as children. Bulimic women had more negative and unusual mealtime experiences than nonbulimic women. Results suggest that sexual abuse may be related to the subsequent onset of bulimia nervosa for some women. PMID- 8472184 TI - Toward a testable developmental model of pedophilia: the development of erotic age preference. AB - Retrospective self-reports about childhood curiosity to see persons in the nude were used to compare the development of erotic sex and age preferences among four groups of males; 46 heterosexual pedophiles, 30 homosexual pedophiles, 462 gynephiles (who erotically prefer physically mature females), and 51 androphiles (who erotically prefer physically mature males). The results suggest (a) throughout this erotic developmental process among males, the establishment of erotic sex preference precedes that of erotic age preference, and (b) a greater proportion of pedophiles than of individuals who prefer physically mature partners remembers curiosity in their own childhood to see nude children without remembering such curiosity in regard to adults. This suggests that in a substantial proportion of pedophiles the occurrence of this paraphilia is predetermined at a very early developmental phase. A further set of retrospective self-reports, obtained from a group of 78 gynephilic university students suggests that at least in gynephiles the erotic appeal of children of the preferred sex ceases by about the time of puberty. This may be an indication that there exists a process of active devaluation of the nonpreferred age bracket, culminating at puberty. PMID- 8472185 TI - The relationship between inflammation and hyperreactivity of the airways in asthma. PMID- 8472186 TI - Modifications of PC20 and maximal degree of airway narrowing to methacholine after pollen season in pollen sensitive asthmatic patients. AB - We examined the effect of cessation of exposure to pollen on non-specific airway responsiveness in 10 grass and/or parietaria pollen sensitive asthmatics. Three methacholine inhalation challenges were performed, the first during pollen season (seasonal period), the second 2 months after the end of season (short time after seasonal period), and the third 5 months after the end of season (long time after seasonal period). The dose-response curves to methacholine were characterized by the PC20 (provocative concentration of methacholine required to produce a 20% fall in FEV1) and maximal response plateau, if possible. A maximal response plateau on the dose-response curve was considered to be present if three or more data points for FEV1 fell within a 5% response range. The challenge was stopped when FEV1 dropped more than 50% or the highest concentration of methacholine (200 mg/ml) was reached. The geometric mean (range) methacholine PC20 increased from 1.08 (0.18-37.22) in the seasonal period to 4.67 (0.71-200) mg/ml during the long time after seasonal period (P < 0.01). On the other hand, in six subjects in whom it was possible to obtain a plateau on at least one challenge, the level of the maximal response decreased from (mean +/- s.e.m.) 44.1 +/- 4.9 in the seasonal period to 30 +/- 4.4 during the long time after seasonal period (P < 0.05). These results suggest that in pollen sensitive asthmatic patients, the cessation of exposure to pollen is associated with a reduction of non-specific bronchial responsiveness (PC20 and maximal degree of airway narrowing to methacholine). PMID- 8472187 TI - IgE-binding components of baker's yeast (Saccharomyces cerevisiae) recognized by immunoblotting analysis. Simultaneous IgE binding to mannan and 46-48 kD allergens of Saccharomyces cerevisiae and Candida albicans. AB - The Saccharomyces cerevisiae allergens were characterized by IgE-immunoblotting with serum samples of 83 patients; 63 represented patients with atopic dermatitis with previous positive skin prick test or RAST for S. cerevisiae, seven patients with AD but negative test results and 13 were non-atopic controls. Disrupted whole body extract of S. cerevisiae was used in the assays. From the patients tested 41 patients with atopic dermatitis appeared positive in IgE immunoblotting revealing 22 IgE stained bands. From these bands 10 represented intermediate allergens, and 12 minor allergens. The most frequent staining was obtained with the 48 kD band (39%). When the staining pattern of 45 kD and 48 kD bands and mannan was compared with Candida albicans allergens or purified baker's yeast enolase a simultaneous binding was seen with the 48 kD band of S. cerevisiae and the 46 kD band of C. albicans and enolase whereas the 45 kD band was neither associated with the 46 kD band of C. albicans nor purified enolase. High molecular weight staining was found in five samples. The staining pattern was associated with the mannose containing structures in parallel with C. albicans. PMID- 8472188 TI - Ciliated cell damage in the bronchial epithelium of asthmatics and non asthmatics. AB - The importance of bronchial epithelial shedding in the pathogenesis of asthma has been highlighted by many investigators as a potential mechanism for bronchial hyperresponsiveness. It has been suggested that this disruption is the result of cytotoxic injury leading to shedding of damaged cells. To investigate whether damaged ciliated epithelial cells can be detected within the bronchial mucosa, we used tannic acid which only permeates disrupted cellular membranes, as a marker of cell damage. Bronchial biopsies from seven asthmatic and six normal subjects, were processed in tannic acid prior to preparation and sectioning for electronmicroscopic examination. Ciliated epithelial cells staining darkly with tannic acid were seen to comprise a similar proportion of the intact portion of bronchial epithelium in both normals and asthmatics (medians 31% vs 40%). We suggest that ciliated epithelial cells are not shed from the bronchial mucosa immediately after damage and that mechanisms other than granulocyte-mediated cytotoxicity may account for epithelial disruption in asthma, possibly involving the selective damage or reduced expression of intraepithelial intercellular adhesion molecules. PMID- 8472189 TI - Occupational allergy to bumble bee venom. AB - The clinical profile of anaphylactic reactions to bumble bees is described and successful immunotherapy with honey bee venom in seven bumble bee allergic patients is reported. The cause of the high frequency of sensitization to pollen in these patients is discussed. PMID- 8472190 TI - In vitro allergenicity of cows' milk substitutes. AB - There are numerous alternatives to cows' milk formula for allergic children. We have investigated the allergenicity of several of these using RAST and RAST inhibition on serum from 16 patients with a known history of cows' milk protein intolerance (CMPI) and 16 atopic controls. A RAST grade of > or = 3 for cows' milk was present in all those with CMPI, whilst all the controls gave RAST of < or = 1. Modified cows' milk formula, goats' infant formula, sheep and goats' milk produced similar results to cows' milk. Only two patients had RAST > or = 3 for soya milk and the soy/beef hydrolysate gave positive results in only three patients. One had positive RAST to Nutramigen and two to Pregestimil. Of the whey hydrolysates investigated, Pepti-junior gave seven positive RASTs whilst we were unable to bind Alfare to the sepharose in sufficient quantities to interpret the results which were negative in all cases. RAST inhibition data on pooled sera from the same patients agreed with the RAST results. The inhibition curves showed high inhibition with goats', sheep, modified cows' milk formula and the casein formula, AL110 (50%). Soy and soy/beef hydrolysate showed a much lower inhibition pattern. Casein hydrolysates showed low inhibition while the whey hydrolysate produced higher inhibition. We have shown that despite claims of low allergenicity, some of these alternative formulae are antigenically recognized in vitro by some cows' milk intolerant patients. PMID- 8472191 TI - Rapid Hymenoptera venom immunotherapy: comparative safety of three protocols. AB - We compared 284 sting-allergic patients treated with either a 4 day (group 1), 6 hr (group 2) or 210 min (group 3) rapid venom immunotherapy (RVIT) protocol using honey bee (HB) or yellow jacket (YJ) venom at cumulative doses of 527.6 micrograms, 226.6 micrograms and 101.1 micrograms respectively. The 4 day protocol involved four times as many injections as the 210 min protocol and twice as many as the 6 hr protocol. Desensitization was conducted in a hospital providing full emergency resuscitation facilities. In group 1, 1 x 100 micrograms boosters were given on days 7, 10, 15 and 45 and, in groups 2 and 3, 2 x 50 micrograms boosters were given on day 15 and 1 x 100 micrograms on day 45. The patients in the three groups were comparable with regard to clinical characteristics and immunological reactivity determined by skin tests. All patients had large local reactions. Systemic reactions (SR) occurred in 28.2% of patients in group 1, 28.6% in group 2 and 6.9% in group 3. The mean total cumulative venom dose (s.e.m.) for occurrence of SR was 123.75 (+/- 24.2) in group 1, 183.27 (+/- 28.5) in group 2, and 36.43 (+/- 9.3) in group 3. HB led to more systemic reactions than YJ venom. The rate of SR decreased when the cumulative venom dose was reduced during RVIT. The median dose was 137.6 micrograms in group 1, 226.6 micrograms in group 2, and 21.1 micrograms in group 3. No systemic reactions were observed after the booster injections. The results of this study suggest that short RVIT protocols with low cumulative doses carry a lesser risk of SR. PMID- 8472192 TI - Allergic reaction to snake venom after repeated bites of Vipera aspis. PMID- 8472193 TI - Allergic skin reaction after inhalation of budesonide. PMID- 8472194 TI - Clinical anatomy of the equine head. AB - This topical presentation emphasizes the structures most likely to be encountered in the diagnosis and treatment of diseases of the equine head. Most of the approaches are from superficial to deep. Anatomic variations associated with aging are described. The larynx and guttural pouches are not included in this article. PMID- 8472195 TI - Diseases of the nasal cavity. AB - Conditions of this portion of the respiratory tract are relatively uncommon. This article reviews these conditions and discusses the different modes of therapy. The conditions covered are redundant alar folds, diseases of the nasal septum, fungal infections, neoplasms, nasal polyps, and ethmoid hematomas. The different surgical approaches to the nasal cavity are reviewed, and surgery of removal of the nasal septum and the alar fold are described. PMID- 8472196 TI - Examination of the oral cavity and routine dental care. AB - Techniques and equipment used to examine the oral cavity thoroughly are explained. Common routine dental procedures described include removal of enamel points, wolf teeth, and retained caps. Abnormalities of the incisors are discussed. PMID- 8472197 TI - Dental surgery. AB - Anatomy, physiology, and diseases of the teeth are presented. Signs of dental disease and techniques for oral and radiographic examination of the teeth are discussed. Surgical procedures described include extraction, repulsion, and endodontic therapy. PMID- 8472198 TI - Paranasal sinuses. AB - Numerous conditions, including trauma, infection, neoplasia, and developmental problems, can affect the paranasal sinuses. Successful resolution of these problems is predicated upon a thorough diagnostic workup to ensure the most accurate presumptive diagnosis. Surgical intervention is enhanced by using approaches that allow wide access to sinus compartments. Rigorous postoperative management is also important to a successful outcome. PMID- 8472199 TI - Head trauma. AB - The equine head is especially prone to trauma from kicks, collisions, entrapments, and falls. The specialized structures of the equine head are important in both function and appearance. When injury causes either loss of function or cosmesis, timely treatment is paramount. This article discusses the occurrence and therapy of trauma to the equine head, including fractures of the mandible and premaxilla, facial bone, hyoid apparatus, and skull base. PMID- 8472200 TI - Reconstructive surgery of selected injuries of the head. AB - Traumatic injuries to the head region of the horse are a common presenting complaint. Because of a copious blood supply, these wounds typically exhibit a tremendous capability for healing. By following the basic principles of wound management and employing a few techniques unique for specific injuries, the healing of these wounds can result in a satisfactory outcome. PMID- 8472201 TI - Neurologic evaluation of the equine head and neurogenic dysphagia. AB - Neurologic evaluation should be performed in horses with diseases of the head. Although neurologic examination should focus on assessing behavior, mental status, and cranial nerve evaluation, evaluation of neurologic function of other body regions should be performed. Neurologic evaluation of the head can be performed expediently by practitioners to provide useful diagnostic and prognostic information. The numerous causes of dysphagia can be classified as obstructive, painful, or neurogenic. Common causes of neurogenic dysphagia are summarized, and methods for initial diagnosis and management are described. Maintaining adequate nutrition and preventing aspiration pneumonia are principal concerns in managing horses with neurogenic dysphagia. PMID- 8472202 TI - Neoplasia. AB - Equine tumors are rather uncommon; however, of the body regions, the head is a relatively common location for neoplasia, including sarcoids and squamous cell carcinomas of the skin, tumors of the sinus/nasal cavity, and bony tumors of the head. Tumors discussed in the article include odontogenic and bony tumors; sarcoids; tumors of the guttural pouch and pharyngeal and oral mucosa; tumors of the larynx; and tumors of the paranasal sinuses and nasal passages. In general, tumors involving deeper structures of the head carry a poor prognosis; however, some tumors such as sarcoids, ossifying fibromas, and osteomas of the paranasal sinus often can be treated effectively by cytoreductive surgery, with or without adjunctive treatment modalities. The clinical signs, prognoses, and therapeutic options for specific tumor types and locations are reviewed. Ophthalmic tumors are not discussed. PMID- 8472203 TI - Miscellaneous conditions of the equine head. AB - Nutritional secondary hyperparathyroidism is associated with horses that are fed diets with an imbalance of calcium and phosphorus or diets containing oxalates. Clinical signs include a shifting lameness, with tenderness of the joints, reluctance to move, or a stiff, stilted gait. Some horses may have broadening of the nasal bones, enlargement of the maxilla and/or the mandible, or a ridge over the nasal bones. Diagnosis may include physical examination findings; analysis of feed; and clinical pathologic data, which may include normocalcemia, normal to increased serum phosphorus, and increased fractional excretion of phosphorus (normal FxP < 0.5%). The primary objective of therapy is to correct the nutritional calcium to phosphorus imbalance. Sialoliths are calcific concretions that develop in the salivary gland or duct. Therapy generally involves surgical removal, and associated complications are uncommon. Obstruction of the nasolacrimal duct occurs most commonly secondary to intraluminal foreign material, although congenital atresia may occur. Clinical signs include epiphora, conjunctivitis, and mucopurulent discharge. Foreign material is often removed by retrograde saline flush and atresia is resolved by surgery. PMID- 8472204 TI - Clinical examination of the equine head. AB - Examination of the equine head should be a routine part of any complete physical examination. It can be performed rapidly and efficiently while providing important information about the health and function of several major body systems. PMID- 8472205 TI - Radiographic examination of the equine head. AB - Radiographic examinations of the equine head can be performed with portable x-ray machines. The views comprising the examination depend on the area of the head being examined. With a knowledge of radiographic anatomy and radiographic signs of disease, valuable diagnostic information can be obtained from the radiographic examination. In addition, the radiographic information can also be used to develop a prognosis and determine the most appropriate therapy. PMID- 8472206 TI - Diagnostic techniques for evaluation of the paranasal sinuses. AB - Physical examination of the paranasal sinuses is often insufficient to confidently reach a conclusion concerning suspected pathology in these cavities. Often, other evaluation techniques are necessary. This article describes physical examination, rhinoscopy, sinus centesis, radiology, and sinus endoscopy of the equine paranasal sinuses. These techniques can be used to diagnosis and determine the cause of most sinus disorders. PMID- 8472207 TI - Congenital diseases of the equine head. AB - Many questions concerning heritability arise when a veterinarian is asked to supervise and treat disease of congenital origin. Genetic counseling, ethics, and legality are often confronted in discussions between animal health professionals and laymen in animal industry. Guidelines have been offered as in the 1984 statement of the Judicial Council of the American Veterinary Medical Association: "Performance of surgical procedures in all species for the purpose of concealing genetic defects in animals to be shown, raced, bred, or sold as breeding animals is unethical. However, should the health or welfare of the individual patient require correction of such genetic defects, it is recommended that the patient be rendered incapable of reproduction." The Australian Veterinary Law, Ethics, Etiquette and Convention declares it fraud to alter a defect for sale purposes and unethical for a veterinarian to perform such treatments. It is permissible to correct defects causing discomfort or inconvenience, but the veterinarian is required to advise appropriate breeding counseling. Genetic counseling has progressed significantly in human medicine. This has been supported by better diagnostic methods for genetic disorders, greater acceptance of preventive measures, and extended screening programs to identify carriers of specific abnormal genes or chromosomal aberrations. Congenital diseases in veterinary medicine are constantly under investigation. The veterinary practitioner must continue to operate with an appreciation of the incomplete understanding of most of these abnormalities and act in accordance with personal ethical judgment and the guidance of the American Veterinary Medical Association when treating the affected individual animal patient. PMID- 8472208 TI - The need for sterilization. PMID- 8472209 TI - Can you read this? PMID- 8472210 TI - Fluoride recommendations released. Canadian Conference on the Evaluation of Current Recommendations Concerning Fluorides, April 9-11, 1992. PMID- 8472211 TI - Handpiece sterilization--the debate continues. PMID- 8472212 TI - Bloodborne pathogens in the health care setting: risk for transmission. Laboratory Centre for Disease Control, Health and Welfare Canada. PMID- 8472213 TI - The effectiveness of the Nd:YAG laser in the treatment of dental hypersensitivity. AB - Dentin hypersensitivity is one of the most painful and least predictably treated chronic conditions in dentistry. The effectiveness of laser therapy in the reduction of dentin hypersensitivity and its effects on pulpal vitality were studied. Nineteen subjects participated in the randomized, double-blind study, and were followed up for three months. Two sites were treated. One received helium neon (He:Ne) laser treatment and the other received He:Ne plus Nd:YAG (He:Ne+Nd:YAG) laser treatment. Laser treatment consisted of 30 millijoules (mJ) to 100 mJ per pulse, at 10 pulses per second (pps) in increments of 10-40 seconds each over a total treatment time of less than two minutes, without local anesthesia. Hypersensitivity was assessed by mechanical stimulus (using a sharp explorer), and thermal stimulus (using a blast of cold air from a dental syringe). Pulpal vitality was measured using an electrical stimulus. The results indicate that immediately following laser treatment and for three months thereafter, the subjects' perceived level of discomfort decreased. He:Ne treatment reduced dentin hypersensitivity to air by 63 per cent and to mechanical stimulation by 61 per cent over three months. The He:Ne + Nd:YAG treatment reduced dentin sensitivity to air by 58 per cent and to mechanical stimulation by 61 per cent. All teeth remained vital after laser treatment, with no adverse reactions or complications. He:Ne and He:Ne + Nd:YAG laser treatment can be used to reduce dentin hypersensitivity without detrimental pulpal effects. PMID- 8472215 TI - New vistas in communication. PMID- 8472214 TI - [The self-aspirating syringe in local anesthesia]. AB - Dentists routinely inject local anesthetic solutions in their daily practice. However, it is important not to inject intravascularly. Consequently, manufacturers offer two types of dental syringes: one with a mechanical aspirating device (harpoon) and the other with a self-aspirating mechanism. We have verified the efficacy of a self-aspirating syringe as presented on the market and another self-aspirating syringe which we lightly modified. PMID- 8472216 TI - Getting the message heard--who should be the messenger? PMID- 8472217 TI - Operation tundra storm. PMID- 8472218 TI - Cutaneous malignant melanoma. PMID- 8472219 TI - Modified technique for radial artery cannulation. PMID- 8472221 TI - The case of Canadian general surgeons: getting the message heard. AB - The problem of physician resources is at the top of the health care policy agenda, and physicians are faced with the challenge of change. General surgeons, like others, must address the changes in health care needs and demands, technology, information and funding. This paper begins with a demographic and workload profile of general surgery based on data provided by the Canadian Medical Association's Physician Resource Questionnaire (PRQ). The findings indicate the following: the supply of general surgical procedures has been declining; general surgeons are older than other specialists; and the proportion of women in general surgery is lower than that of the profession as a whole. The practice profile of general surgery is also changing because of advances in technology and information and the changing practice of subspecialists. Changes affecting general surgery raise important questions regarding future physician resource policies. The medical profession's involvement in the area of physician resources at the national level is outlined, with a particular focus on the role of the Canadian Medical Association. It is important that general surgeons become involved in the discussion, since the policy decisions made today will affect the future practice of general surgery. PMID- 8472220 TI - State of the art of venous investigation and treatment. AB - OBJECTIVE: To discuss current investigative and treatment modalities in all venous problems, ranging from telangiectasia to chronic venous insufficiency. DATA SOURCES: A thorough review of current literature plus the author's personal experience and ideas. DATA SYNTHESIS: Clinical interest and research into venous disease is increasing. Despite advanced investigative technology, the definitive management of chronic venous insufficiency remains controversial. Deep valvular reconstruction is now possible; however, indications for this type of procedure are rare. CONCLUSION: The renewed interest in venous disease will likely lead to specific treatments for all aspects of venous disease, especially for chronic venous insufficiency. PMID- 8472222 TI - A perspective on tumour progression. AB - During their natural history, tumours may acquire new phenotypic traits. This process, tumour progression, becomes clinically important when tumours acquire the ability to invade and metastasize or when they develop drug resistance. An acquired genetic instability modulated by selection likely contributes to this progression. More than one genetic mechanism is probably involved, a small number of point mutations being complemented by karyotypic events, gene amplification and altered gene expression. More complicated traits, such as the ability to invade and metastasize, may be acquired through the inappropriate and disorganized reexpression of genetic programs suppressed during embryologic development. PMID- 8472223 TI - Pin-site radioulnar synostosis after external fixation of a distal radial fracture: two case reports. AB - Complications of distal radial fracture and external fixation are common, but the authors report, in two patients, a previously unrecognized complication, that of radioulnar synostosis. In both cases the proximally placed pins extended across the interosseous region, and the distal ends were adjacent to the ulna. Hematoma and osseous debris were introduced into the interosseous region. Several weeks after the external fixator was removed, the patients were noted to have a restricted range of pronation and supination. A radioulnar synostosis had formed across the interosseous region. Resection of the synostosis restored pronation and supination. With careful pin placement this complication will be avoided. PMID- 8472224 TI - Initial nonfunction in cadaveric renal transplantation. AB - Patients who receive a kidney transplant that does not function immediately have more complications and decreased graft survival than patients whose allografts function immediately. To determine the causes of initial nonfunction (INF), the authors reviewed 188 consecutive cadaveric kidney transplants performed between 1985 and 1988 at the University Hospital, London, Ont. Data were collected on 16 putative risk factors for INF, which were divided into three categories: donor, recipient and technical. INF was defined as the need for dialysis within 7 days of transplantation. Forty-eight (26%) of the 188 allografts had INF, 6 of which never functioned. Univariate analysis identified five variables associated with increased risk of INF: no donor dopamine use, back-table flush, single-organ retrieval, exchanged kidney and prolonged cold ischemic time. Multivariate analysis, however, identified only three variables associated with INF: cerebrovascular accident as the cause of donor death, no donor dopamine use and single-organ retrieval. The authors recommend (a) low-dose dopamine therapy for all donors and (b) multiorgan retrieval to produce quality kidneys for transplantation. PMID- 8472225 TI - Verrucous carcinoma of the genital tract: is it a distinct entity? AB - Between 1974 and 1985, 16 patients (7 men, 9 women) with a diagnosis of genital verrucous carcinoma were identified from the cancer registry of the Tom Baker Cancer Centre in Calgary. All the men had lesions on the penis. In the women, five lesions were on the vulva, four were on the cervix and two were on the vagina (two women each had two involved sites). The histologic slides from the surgically excised specimens were reviewed, and, by applying strict criteria, all cases could be reclassified as giant condyloma (five cases), intraepithelial neoplasia with or without condylomatous features (eight cases) or invasive squamous cell carcinoma (five cases). The authors believe that, in genital lesions associated with the human papillomavirus, a diagnosis of verrucous carcinoma is nonspecific and may lead to inappropriate clinical management. PMID- 8472226 TI - "No stent, no diversion" Mathieu hypospadias repair. AB - The Mathieu procedure is a surgical technique for anterior hypospadias repair. The disadvantage of this technique is the prolonged hospital stay associated with postoperative urinary diversion. In an effort to reduce the length of hospital stay the authors carried out a prospective study to determine the usefulness of urethral stents and urinary diversion after Mathieu repair. Seventeen boys (mean age 4.1 years) formed the experimental group, and 19 boys (mean age 4.6 years) served as controls. Urinary diversion and urethral stents were used postoperatively in the control group but not in the experimental group. After a minimum of 6 months of observation the complications noted in both groups were found to be similar. The authors conclude that urinary diversion and urethral stents have no beneficial effects on surgical outcome but do prolong hospital stay. PMID- 8472227 TI - The morbidity of abdominal hysterectomy. AB - OBJECTIVE: To determine the morbidity of abdominal hysterectomy. DESIGN: Descriptive. Physician billings to the Quebec Health Care Plan in the 1-month period after abdominal hysterectomy were examined. SETTING: Operations performed in 102 hospitals in the Province of Quebec between Jan. 1, 1989, and Mar. 31, 1989, were selected. PATIENTS: The study group included 3322 patients who had abdominal hysterectomy. Patients who had vaginal or abdominal hysterectomy for invasive cancer or pregnancy-related complications were excluded. A patient was considered to be morbid if the physician's intervention indicated concern for the patient's well-being. MAIN OUTCOME MEASURES: Multiple logistic regression analysis to determine the adjusted rate ratio for inclusion in a categorical list of morbid patients among different subsets of surgeons, hospitals and patients. RESULTS: Postoperative morbidity occurred in 646 patients (19.5%), who spent an average of 1.7 days longer in the hospital than patients with no postoperative morbidity. There were two postoperative deaths (0.1%). Forty-nine patients (1.5%) had postoperative surgical intervention. On 119 occasions (3.6%), patients were treated in the intensive care unit. A consultation was given by a medical specialist in 303 cases (9.1%). The rate ratio for postoperative morbidity was not significantly affected by years in practice or specialty of the surgeon but was increased for operations performed in mid-sized hospitals. The strongest predictor of postoperative morbidity was pre-existing medical disorder (RR). CONCLUSION: The major causes of morbidity in patients who undergo abdominal hysterectomies are medical rather than surgical. PMID- 8472228 TI - An unusual intraoperative complication of stapled colorectal anastomosis: report of a case and review of the literature. AB - The unusual intraoperative complication of inadvertent formation of a stapled colovaginal anastomosis is described in a 61-year-old woman with diverticular disease. Intraoperative complications of linear staplers, linear cutters and circular end-to-end anastomotic staplers are reviewed, as are methods of prevention and management of such complications. The discussion focuses mainly on the complications that may arise in low anterior resection. They are more likely due to operator error than to instrument failure. PMID- 8472229 TI - Foot infections in diabetics: the antibiotic choice. AB - The authors studied 59 diabetics with foot infections to determine the organisms responsible and the sensitivity to antibiotics. All infections were polymicrobial (aerobic and anaerobic). On average 3.2 isolates per culture were obtained from the depth of the infection. The commonest organisms in order of frequency were: Staphylococcus aureus, beta-hemolytic streptococci, Proteus sp., Bacteroides sp., enterococci, Klebsiella sp. and Pseudomonas aeruginosa. A combination of piperacillin and cloxacillin is recommended as initial therapy for foot infections in diabetic patients because it was found to be effective for 73% of the causative microorganisms. PMID- 8472230 TI - Foreign bodies in the rectum. AB - Although infrequent, rectal foreign bodies present a challenge in management. The authors report on their experience with 29 patients who had rectal foreign bodies. Emergency-department procedures included rectal examination, proctoscopy and abdominal radiography. Soft or low-lying objects having an edge could be grasped and removed safely in the emergency department, but grasping hard objects was potentially traumatic and occasionally resulted in upward migration toward the sigmoid. Operating-room procedures included anal dilatation under general anesthesia, transrectal manipulation, bimanual palpation if necessary and withdrawal of the foreign body. In two cases, rectal mucosa was trapped--in an open deodorant bottle in one patient and in a curtain rod in the second patient; operative release of the mucosa enabled safe removal. Two patients presented with peritonitis; both had "broomstick" injuries and required proximal colostomy. Five patients had perianal sepsis due to inadvertently ingested pieces of wood (three) and chicken bones (two). The mean hospital stay was 3 days (range from 6 hours to 6 days). There were no deaths. Because of the potential complications, rectal foreign bodies should be regarded seriously and treated expeditiously. PMID- 8472231 TI - Soft tissue sarcomas: a plea for proper management. AB - Although soft tissue sarcomas are relatively uncommon, they often occur in young patients and if properly treated are often curable. Unfortunately, inappropriate approaches to biopsy before adequate staging may compromise a successful outcome. The roles of diagnostic imaging (particularly magnetic resonance imaging) in adequate preoperative evaluation and staging and the fundamental principles of surgical management are discussed. PMID- 8472232 TI - The Advanced Trauma Life Support Program in Manitoba: a 5-year review. AB - Twenty Advanced Trauma Life Support (ATLS) courses were conducted at the University of Manitoba between 1982 and 1987. There were 302 registrants, 95 of whom were from rural communities. Twelve registrants failed the course. The impact of the program was assessed by questionnaire (68.8% response overall). The response from department heads of surgery in urban hospitals was 87.5% and from surgeons in rural areas 50%. Fifty-eight percent of rural surgeons, 62.5% of urban surgeons and 75% of urban emergency-department directors claimed they could identify those who had attended an ATLS course by the increased confidence demonstrated and the use of more timely and appropriate consultation and treatment. Thirty percent of rural surgeons, 37% of urban surgeons and 42% of emergency-department directors claimed that mortality and morbidity were decreased when care was provided by ATLS-trained physicians. The remainder were undecided because of lack of information. Ninety-three percent of respondents indicated that the course increased their confidence, trauma capability and ability to communicate with consultant trauma surgeons. Fifty-two percent thought the course should be mandatory for all physicians, and 100% thought it should be mandatory for all emergency-department physicians. The data suggest that although most physicians treat fewer trauma patients 5 years after their ATLS training, the course is still highly recommended, and it has improved trauma care. Although the ATLS program was intended primarily for rural physicians, more urban-based physicians registered for it. PMID- 8472234 TI - Fulfilling a wish. AB - As awareness of the need for organ donations grows, so does the frequency of requests by terminal patients to become donors. Recently, we experienced just such a phenomenon at Plummer Memorial Hospital. PMID- 8472233 TI - A comparison between expanded polytetrafluoroethylene and plasma tetrafluoroethylene grafts for hemodialysis access. AB - Animal studies have indicated that plasma tetrafluoroethylene (TFE) may be a better prosthetic material than expanded polytetrafluoroethylene (ePTFE) for arteriovenous access in patients who require hemodialysis because it combines the advantages of both Dacron and Teflon. A randomized clinical trial to compare the two materials was conducted between May 1987 and January 1989. Forty-four patients were enrolled, 22 in each group. The status of the grafts was monitored for at least 18 months. The patency rate for plasma TFE was 59% and for ePTFE was 64%. Kaplan-Meier analysis and Wilcoxon testing revealed no statistical differences between the two groups. Four grafts became infected, two in each group, and one aneurysm developed. Despite its theoretical advantages, plasma TFE was found to be similar to ePTFE as a graft material for hemodialysis. PMID- 8472235 TI - Medication non-compliance. AB - Medication non-compliance is a perplexing, pervasive and poorly understood problem. Historically, the medical community viewed it as an act of defiance. But in recent years nurses have challenged that position, instead seeing non compliance as behavior that can be intentional or unintentional; detrimental or, on occasion, beneficial. PMID- 8472236 TI - Nursing: the endangered profession? AB - The history of nursing illustrates patterns that continue to threaten the recruitment and retention of nurses today. Three contemporary examples illustrate key dilemmas the nursing profession is facing. They also provide us with clues to patterns and themes that have recurred throughout our history. PMID- 8472237 TI - Rekindling the nursing diagnosis flame. AB - In today's complex and rapidly changing health care environment, it is not enough for nurses to possess advanced technological skills. Rather, they need clinical judgement, decision-making and diagnostic skills far beyond previous expectations. PMID- 8472238 TI - Treating nocturnal enuresis. AB - Nocturnal enuresis, commonly known as bedwetting, is described in documents dating from 1550 BC. Derived from the Greek word enourein, meaning "in urine" or "inability to control urination," it occurs in 15 to 20 per cent of five year olds and is twice as common in boys as girls. Indeed, no cure has yet been found and thousands of children and their families live with the distress the condition causes. Among affected children, this often includes behavioral problems and low self-esteem. PMID- 8472239 TI - Innovation through collaboration. AB - In light of the Canadian Nurses Association's position that the baccalaureate degree would be the requirement for entry to practice by the year 2000, plus evidence of a rapidly changing health care system, changing client characteristics, and on-going economic constraints, administrators of nursing programs in Edmonton recognized the need for a more process-oriented curriculum to prepare nurses to be more capable of facing future challenges. Not surprisingly, limited funds and differing human and material resources meant they could not complete a major curriculum change individually. Collaboration proved to be the key that increased access to baccalaureate nursing education in Alberta. PMID- 8472240 TI - Toxoplasmosis and pregnancy. AB - Toxoplasmosis is an infection caused by the protozoa toxoplasma gondii that is prevalent worldwide. The protozoa was given its name when it was first isolated in 1909 in Africa in a rodent, Ctenodactylus gondii. It can be contracted by eating infected meat or eggs that are raw or undercooked, or through contact with the feces of an infected cat. More dangerously, it can be congenitally acquired by transfer through the placenta if the mother contracts the disease during pregnancy. Although the flu-like symptoms of the disease can be mild in adults (fatigue, muscle spasms, lymphadenopathy) or often subclinical, infants who acquired the disease congenitally face severe mental and physical problems. PMID- 8472241 TI - Unmarried motherhood. AB - In the past, the children of unmarried women were stigmatized and treated as second-class citizens by both society and the law. As societal attitudes have become more tolerant, however, the laws have been changed to ensure equality for all children. Despite this, there is little evidence to show that the children of unmarried mothers receive the rights guaranteed them by law, or that the birth parents and caregivers are even aware of those rights. PMID- 8472242 TI - Powering up our professional image. AB - Traditionally, women have been society's healers. The practices of healing were closely associated with organized churches. Nursing developed to give women an opportunity to do God's work. Since caring and nurturing were believed to be innate characteristics of women, nursing offered an opportunity to express these attributes in an appropriate and productive way. PMID- 8472243 TI - [Preoperative structured patient education]. AB - This article describes the factors that motivated the nursing staff of the cardiac surgery unit at the Royal Victoria Hospital in Montreal, to revise their preoperative teaching program. The motivating factors described are the length of the preoperative waiting period; the level of preoperative anxiety; the decreased length of hospital stay; the dissatisfaction of the nursing staff with current patient teaching practices; and the lack of available resources. The reorganization of the teaching program was based upon the previously described factors combined with a review of the literature that demonstrated the impact of preoperative anxiety, emotional support and psycho-educational interventions upon the client's recovery. The goals of the new teaching program are to provide the client and the family with cognitive and sensory information about the client's impending hospitalization, chronic illness and necessary lifestyle modifications. The program consists of a system of telephone calls during the preoperative waiting period; a videotape viewing; a tour of the cardiac surgery unit; informal discussion groups; and the availability of nursing consultation to decrease preoperative anxiety. The end result of these interventions is more time for client support and integration of necessary information by the client and family. This kind of program has the potential to provide satisfaction at many levels by identifying client's at risk; increasing client knowledge; increasing support; decreasing anxiety during the preoperative waiting period; and decreasing the length of hospital stay. The nursing staff gained a heightened sense of accomplishment because the program was developed according to the nursing department's philosophy, which includes primary nursing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472244 TI - [Quality of services in a small hospital]. AB - The nursing services department of a 64 bed hospital in Caraquet, New Brunswick, (serving a widespread population of 25,000 people) decided to check the quality of care offered to their patients. A search was conducted among numerous quality of care management models to find the one that best suited their needs. They chose a structured quality appraisal and management program currently being used by the Royal Victoria Hospital in Montreal. The author outlines the way quality assurance directors in this Montreal hospital empower their health care providers. The author describes the concept of quality and summarizes the oriental and occidental ideologies that influence it. The nursing staff's perception of the essential elements of quality assurance are explained and the stages are identified. The author maintains that decentralization and delegation empowers individuals and instills confidence while maintaining the essential personal touch. She believes that the organization of the future is one that will promote teamwork. She also believes that motivation, participative management and workplace satisfaction promote quality care--"care that doesn't cost a dime." This program has numerous advantages. It allows employees to fully participate in the process. It also averts potential problems, and provides employees with the ability to discover and problem solve when necessary. It also allows for the strengths and weaknesses of each service to be outlined and identified deficiencies corrected. PMID- 8472245 TI - Pathogenesis and pathophysiology of bacterial meningitis. AB - Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder. PMID- 8472246 TI - Role of iron in regulation of virulence genes. AB - The abilities of bacterial pathogens to adapt to the environment within the host are essential to their virulence. Microorganisms have adapted to the iron limitation present in mammalian hosts by evolving diverse mechanisms for the assimilation of iron sufficient for growth. In addition, many bacterial pathogens have used the low concentration of iron present in the host as an important signal to enhance the expression of a wide variety of bacterial toxins and other virulence determinants. The molecular basis of coordinate regulation by iron has been most thoroughly studied in Escherichia coli. In this organism, coordinate regulation of gene expression by iron depends on the regulatory gene, fur. Regulation of gene expression by iron in a number of pathogenic organisms is coordinated by proteins homologous to the Fur protein of E. coli. Additional regulatory proteins may be superimposed on the Fur repressor to provide the fine tuning necessary for the precise regulation of individual virulence genes in response to iron and other environmental signals. Studies of the mechanisms of regulation of iron acquisition systems and virulence determinants by iron should lead to a better understanding of the adaptive response of bacteria to the low iron environment of the host and its importance in virulence. PMID- 8472250 TI - Synthesis and conformational analysis of muramic acid delta-lactam structures and their 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl) derivatives, characteristic of bacterial spore peptidoglycan. AB - 1,6-Anhydro-4-O-benzyl-beta-muramic acid 1',2-lactam (2) was prepared by reduction of 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-3-O-[(R)-1- methoxycarbonylethyl]-beta-D-glucopyranose (1) followed by cyclisation. Debenzylation of 2 (-->3) and glycosylation of HO-4 with 3,4,6-tri-O-acetyl-2- deoxy-2-phthalimido-beta-D-glucopyranosyl chloride afforded 75% of a beta-(1-->4) linked disaccharide derivative (7). Removal of the Phth group from 7, then acetylation, and O-deacetylation yielded 4-O-(2-acetamido-2-deoxy-beta-D glucopyranosyl)-2-amino-1,6-anhydro-3-O- [(R)- 1-carboxyethyl]-2-deoxy-beta-D glucopyranose 1',2-lactam (10) Acetolysis of the 1,6-anhydro ring in the 4 acetate (4) of 3 and the 3',4',6'-triacetate (9) of 10, with saponification of the products 5 and 11, afforded 2-amino-3-O- [(R)-1-carboxyethyl]-2-deoxy-D glucopyranose 1',2-lactam (6) and 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl) 2-amino-3- O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranose 1',2-lactam (12), respectively. The structure of 12 corresponds to that of the disaccharide unit characteristic of the glycan chains of bacterial spore peptidoglycan. 1H NMR spectroscopy indicated that the beta-D-glucopyranose ring in the 1,6-anhydro 1',2 lactam derivatives adopts the BO,3 conformation. On cleavage of the 1,6-anhydro ring by acetolysis, the D-glucopyranose ring adopts the 4C1 conformation. X-ray analysis of 2, 4, and 5 confirmed the proposed structures. Molecular mechanics and molecular dynamics simulations were used to follow the transformation of the BO,3 conformation of the D-glucopyranose ring via transition states to the 4C1 form. PMID- 8472251 TI - Iodonium ion-assisted synthesis of a haptenic tetrasaccharide fragment corresponding to the inner cell-wall glycopeptidolipid of Mycobacterium avium serotype 4. AB - Condensation of ethyl 2,4-di-O-benzoyl-1-thio-alpha-L-rhamnopyranoside with ethyl 3-O-benzyl-4-O-chloroacetyl-2-O-methyl-1-thio-beta-L-fucopyranoside in the presence of iodonium di-sym-collidine perchlorate afforded exclusively ethyl 2,4 di-O-benzoyl-3-O-(3-O-benzyl-4-O- chloroacetyl-2-O-methyl-alpha-L-fucopyranosyl) 1-thio-alpha-L-rhamnop yra noside. This disaccharide derivative was extended at C 1 with 3-benzyloxycarbonylaminopropyl 6-deoxy-3,4-O-isopropylidene-alpha-L- talopyranoside, using N-iodosuccinimide and triflic acid as the catalyst, to furnish 3-benzyloxycarbonylaminopropyl 6-deoxy-2-O-[2,4-di-O-benzoyl-3-O-(3-O benzyl-4-O-chloroacetyl-2-O-me thy l- alpha-L-fucopyranosyl)-alpha-L rhamnopyranosyl]-3,4-O-isopropylidene-alp ha-L- talopyranoside (20). Selective removal of the chloroacetyl group from 20, followed by condensation with ethyl 2,3-di-O-benzoyl-4-O-methyl-1-thio-alpha-L- rhamnopyranoside in the presence of the same thiophilic promoter, yielded a fully protected tetrasaccharide derivative. Deprotection of the latter gave the target compound 3-aminopropyl 6 deoxy-2-O-[3-O-[2-O- methyl-(4-O-methyl-alpha-L-rhamnopyranosyl)-alpha-L fucopyranosyl]-alpha -L- rhamnopyranosyl]-alpha-L-talopyranoside (1). PMID- 8472248 TI - Pathogenesis of infections related to intravascular catheterization. AB - Over the past few decades, there have been major technological improvements in the manufacture of intravenous solutions and the manufacture and design of catheter materials. However, the risk of infection in patients receiving infusion therapy remains substantial, in part because of host factors (for example, increased use of immunosuppressive therapy, more aggressive surgery and life support, and improved survival at the extremes of life) and in part because of the availability of catheters that can be left in place for very long periods. Microbial components of normal skin flora, particularly coagulase-negative staphylococci, have emerged as the predominant pathogens in catheter-associated infections. Therefore, efforts to prevent skin microorganisms from entering the catheter wound (such as tunnelling of catheters and use of catheter cuffs and local antimicrobial agents) are logical and relatively effective. The specific properties of microorganisms that transform normally harmless commensals such as coagulase-negative staphylococci into formidable pathogens in the presence of a plastic foreign body are being explored. For example, Staphylococcus epidermidis elaborates a polysaccharide adhesin that also functions as a capsule and is a target for opsonic killing. However, the interactions between microorganism and catheter that lead to adherence, persistence, infection, and dissemination appear to be multifactorial. PMID- 8472252 TI - A convenient synthesis of lacto-N-biose I [beta-D-Gal p-(1-->3)-beta-D- Glc pNAc] linked oligosaccharides from phenyl O-(tetra-O-acetyl-beta-D- galactopyranosyl) (1-->3)-4,6-di-O-acetyl-2-deoxy-2-phthalimido-1-thio- beta-D- glucopyranoside. PMID- 8472247 TI - Physical and chemical methods for enhancing rapid detection of viruses and other agents. AB - Viral replication events can be enhanced by physical, chemical, or heat treatment of cells. The centrifugation of cells can stimulate them to proliferate, reduce their generation times, and activate gene expression. Human endothelial cells can be activated to release cyclo-oxygenase metabolites after rocking for 5 min, and mechanical stress can stimulate endothelial cells to proliferate. Centrifugation of virus-infected cultures can increase cytopathic effects (CPE), enhance the number of infected cells, increase viral yields, and reduce viral detection times and may increase viral isolation rates. The rolling of virus-infected cells also has an effect similar to that of centrifugation. The continuous rolling of virus infected cultures at < or = 2.0 rpm can enhance enterovirus, rhinovirus, reovirus, rotavirus, paramyxovirus, herpesvirus, and vaccinia virus CPE or yields or both. For some viruses, the continuous rolling of infected cell cultures at 96 rpm (1.9 x g) is superior to rolling at 2.0 rpm for viral replication or CPE production. In addition to centrifugation and rolling, the treatment of cells with chemicals or heat can also enhance viral yields or CPE. For example, the treatment of virus-infected cells with dimethyl sulfoxide can enhance viral transformation, increase plaque numbers and plaque size, increase the number of cells producing antigens, and increase viral yields. The infectivity of fowl plague virus is increased by 80-fold when 4% dimethyl sulfoxide is added to culture medium immediately after infection. The heat shocking of virus-infected cells also has been shown to have a stimulatory effect on the replication events of cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus. The effects of motion, chemicals, or heat treatments on viral replication are not well understood. These treatments apparently activate cells to make them more permissive to viral infection and viral replication. Perhaps heat shock proteins or stress proteins are a common factor for this enhancement phenomenon. The utility of these treatments alone or in combination with other methods for enhancing viral isolation and replication in a diagnostic setting needs further investigation. PMID- 8472253 TI - A novel regioselective desulfation of polysaccharide sulfates: Specific 6-O desulfation with N,O-bis(trimethylsilyl)acetamide. PMID- 8472249 TI - Paracoccidioidomycosis: an update. AB - This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43 kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems. PMID- 8472254 TI - The gum exudate of Encephalartos friderici-guilielmi. AB - Studies of the structure of the polysaccharide gum exudate from Encephalartos friderici-guilielmi (a Cycad) confirmed its resemblance to those from other species of the same genus. Partial acid hydrolysis gave numerous products which showed a strong correlation with those from E. longifolius gum. The course of sequential Smith degradations was monitored by analysis of the molecular weights and composition of the products. The mild acid-hydrolysis step of the Smith degradation proceeded in two stages, the second being very slow but yielding a (1 ->3)-D-galactan with < 20% of other residues (D-mannose, and some L-arabinose and L-rhamnose). A tentative formulation of the gum shows L-rhamnose and D-glucuronic acid residues exterior to a branched D-galactan framework; these structures are 3 linked to D-mannose, through D-galactopyranosyl or possibly L-arabinopyranosyl residues, within mannoglucuronoglycan chains. Other units occupy O-4 of D mannose. PMID- 8472256 TI - Synthesis of plasmalopsychosines A and B two novel lysosphingolipids found in human brain. PMID- 8472255 TI - Structure elucidation of a novel acidic tetrasaccharide and hexasaccharide derived from a chemically modified heparin. PMID- 8472257 TI - Determination of the position of the O-acetyl group in a beta-(1-->4)-mannan (acemannan) from Aloe barbardensis Miller. PMID- 8472258 TI - Location of a second O-acetyl group in xanthan gum by the reductive-cleavage method. PMID- 8472259 TI - Selective deacylation on the glucosyl moiety of octa-O-acetylsucrose by enzymic hydrolysis: formation of 2,1',3',4',6'-penta-O-acetylsucrose. PMID- 8472260 TI - Inclusion complexes of cyclomaltoheptaose (beta-cyclodextrin) and its methylated derivatives with the main components of the pheromone of the olive fruit fly. AB - The inclusion complexes of cyclomaltoheptaose (beta CD) and heptakis(2,3,6-tri-O methyl)cyclomaltoheptaose (TM-beta CD) with the four major components of the pheromone of the olive fruit fly (Dacus oleae), namely 1,7 dioxaspiro[5.5]undecane, (-)-alpha-pinene, nonanal, and ethyl dodecanoate, and the complex of heptakis(2,6-di-O-methyl)cyclomaltoheptaose (DM-beta CD) with 1,7 dioxaspiro[5.5]undecane were studied. The complexes were characterised in the solid state by differential scanning calorimetry and X-ray powder diffraction. In aqueous solution, the structure of the complexes was investigated by 1H NMR spectroscopy. In solution, 1,7-dioxaspiro[5.5]undecane, (-)-alpha-pinene, and nonanal enter the cavity of the cyclo-oligosaccharides. Association constants for some of these complexes were also measured. The complexes of ethyl dodecanoate did not provide evidence of their structure in solution. This was attributed to the existence of negligible amounts of these complexes in water due to the combined effects of low solubility and low association constant. PMID- 8472261 TI - Crystal structure of 2,5-anhydro-1-O-(p-tolylsulfonyl)-D-mannitol. AB - 2,5-Anhydro-1-O-(p-tolylsulfonyl)-D-mannitol, C13H18SO7, Mr = 318.4, monoclinic, C2, a = 26.370(6), b = 7.9741(11), c = 6.6801(6) A, beta = 91.401(11) degrees, V = 1404.3(6) A3, Z = 4, DX = 1.506 g/cm3, CuK alpha, lambda = 1.54184 A, mu = 23.03 cm-1, F(000) = 672, T = 296(1) K, R = 0.042 for 2832 observations with I > 3 sigma (I) (of 2864 unique data). On the esterified side of the molecule, three bond lengths and three bond angles show small changes compared to the unesterified side, which is similar to the symmetrical parent compound, 2,5 anhydro-D-mannitol. The conformation of the five-membered ring is E5 with P = 49.3 degrees and tau m = 38.1 degrees. The hydroxymethyl groups adopt g+ and g- dispositions similar to the parent molecule. The three hydroxyl groups are involved in a network of intermolecular hydrogen bounds both as donors and acceptors. PMID- 8472262 TI - The crystal and molecular structure of beta-D-fructofuranosyl alpha-D xylopyranoside hemihydrate. AB - The crystal and molecular structure of beta-D-fructofuranosyl alpha-D xylopyranoside (xylosucrose) hemihydrate, C11H20O10.0.5H2O, is orthorhombic, P2(1)2(1)2, with a = 20.919(5), b = 18.727(2), c = 7.071(1) A, V = 2770.1(2) A3, Z = 8, and Dx = 1.541 g.cm-3. The structure was solved by direct methods and refined to R = 0.040 for 2564 observed reflections. Two independent xylosucrose molecules exist in the unit cell, and their conformations about the 1-->2' glycosidic bond are similar to sucrose. The orientations of the primary hydroxyl groups in the two molecules differ. An O-1'...O-2 intramolecular hydrogen bond was observed in the one molecule, while an O-6'...O-5 intramolecular hydrogen bond was observed in the other involving disorder of O-6'. PMID- 8472263 TI - A new approach to the chemical synthesis of the trisaccharide, and the terminal di- and mono-saccharide units of the major, serologically active glycolipid from Mycobacterium leprae. AB - The key intermediates for the synthesis of p-trifluoroacetamidophenyl O-(3,6-di-O methyl-beta-D-glucopyranosyl)-(1-->4)-O-(2,3-di-O-methyl-alp ha-L- rhamnopyranosyl)-(1-->2)-3-O-methyl-alpha-L-rhamnopyranoside (15), as well as p trifluoroacetamidophenyl O-(3,6-di-O-methyl-beta-D- glucopyranosyl)-(1-->4)-2,3 di-O-methyl-alpha-L-rhamnopyranoside (29), were the methyl and ethyl O-(2-O benzyl-4,6-O-benzylidene-3-O-methyl-beta- D-glucopyranosyl)-(1-->4)-2,3-O diphenylmethylene-1-thio-alpha-L- rhamnopyranosides (10 and 24). Dichloroalane treatment of 10 and 24 removed the diphenylmethylene group, liberating HO-2 and HO-3 of the rhamnopyranoside residue, and opened the benzylidene acetal regioselectively to give the 4-O-benzyl-glucopyranosyl disaccharides. Methylation of the free OH groups resulted in the tetra-O-methyl 1-thio disaccharides (12 and 26), useful as glycosyl donors. Introduction of these temporary blocking groups allowed a drastic reduction in the number of synthetic steps to the target compounds. PMID- 8472264 TI - Ischaemic myocardial injury and ventricular remodelling. PMID- 8472265 TI - Stress proteins--an endogenous route to myocardial protection: fact or fiction? PMID- 8472266 TI - Understanding the jargon: a glossary of terms used (and misused) in the study of ischaemia and reperfusion. PMID- 8472267 TI - Lack of inotropic effect of cyclosporin A in isolated guinea pig left atria. AB - OBJECTIVE: Cyclosporin A is being widely used to prevent graft rejection in organ transplantation and to treat autoimmune diseases. Since various toxic side effects have been observed, the aim of this study was to look for even a subtle deleterious effect of cyclosporin A on cardiac inotropy in electrically stimulated guinea pig left atria. METHODS: The left atrial muscles of guinea pigs, in Tyrode's solution containing 2.7 or 5.4 mM potassium, were electrically stimulated by one of two methods: (1) continuously at 3 Hz, during which cyclosporin A was applied cumulatively (from 10(-9) to 10(-5) M); or (2) stimulated intermittently at 2.5 Hz in 5 mM cyclosporin A, with rest periods of 4 s duration interposed every 4 min. The effects of cyclosporin A on contractile force were observed for 150 min in the first stimulation method, and the effects on the steady state contractile force and amplitude of post-rest contraction were observed for 240 min in the second method. RESULTS: The steady state contractile force of the atria declined within the 4 h period at 2.7 mM potassium in Tyrode's solution both in the cyclosporin A group (n = 10) and in the control group (n = 5) to 68(SD 11)% and to 63(4)%, respectively. After 4 h the amplitudes of the post-rest contraction were 101(16)% and 101(4)% in cyclosporin A and control groups, respectively. At 5.4 mM potassium, the following values were obtained (cyclosporin A v control): steady state force 70(8)% (n = 11) v 69(8)% (n = 5); post-rest force 105(9)% v 102(7)%. CONCLUSIONS: Cyclosporin A does not influence the steady state contractile force or the amplitude of the post-rest contraction, suggesting the absence of inotropic effects on isolated guinea pig left atria. PMID- 8472268 TI - Increased elastin content and decreased elastin concentration may be predisposing factors in dissecting aneurysms of human thoracic aorta. AB - OBJECTIVE: The aim was to investigate whether changes in elastin distribution in the thoracic aorta are associated with occurrence of dissecting aneurysms. METHODS: Ten thoracic aortas were obtained at necropsy from dissections (mean patient age 74.3 years, SD 7.3) and from 10 age matched controls (mean age 73.1 years, SD 6.9). Full wall thickness samples (1 cm diameter) were taken at 12 sites between heart and diaphragm from aortas of dissections and controls. Elastin content (total elastin per sample), concentration (mg.mg-1 tissue dry weight), degree of cross linking, and amino acid composition were determined. RESULTS: Comparison of areas of dissected aortas involved in dissection with corresponding areas of controls showed significant increases in content of elastin (p < 0.05), content and concentration of proteins other than elastin and collagen (p < 0.01), and a decrease in elastin concentration (p < 0.01). Comparison of areas remote from dissection with corresponding areas in controls showed no significant differences except for decreased elastin concentration (p < 0.05). There were no differences in elastin cross linking. Elastin from dissected aortas had a higher content of aspartate, threonine, serine, glutamate, and lysine and a lower content of glycine, alanine, and valine than elastin from controls (p < 0.05). CONCLUSIONS: Biochemical changes in dissections are localised to the dissected area, with increased deposition of elastin, collagen, and other proteins. The altered matrix composition is likely to change the mechanical properties, possibly increasing the tendency to rupture. PMID- 8472269 TI - Effects of arterial distensibility on left ventricular ejection in the depressed contractile state. AB - OBJECTIVE: The aim was to evaluate the effects of arterial distensibility on ventricular ejection in various ventricular contractile states: (1) control; (2) a regionally depressed contractile state due to left circumflex coronary artery occlusion (ligation); (3) a globally depressed contractile state induced by lignocaine (lignocaine); and (4) a globally augmented contractile state due to dobutamine infusion (dobutamine). METHODS: Arterial compliance was decreased from 2.3 x 10(-4) dyne-1.cm5 (C2.3) to 0.4 x 10(-4) dyne-1.cm5 (C0.4), maintaining other afterload components and left ventricular end diastolic pressure constant. Nine excised perfused and paced canine hearts, supported from donor dogs, were used. RESULTS: In control, ligation, lignocaine, and dobutamine groups, the difference in cardiac output between the compliance values of C0.4 and C2.3 was 124(SEM 32), 204(36), 163(33), and 130(24) ml, respectively. Thus cardiac output at C0.4, as a percentage of that at C2.3, was 88(2.8)% (control), 75(2.9)% (ligation), 82(2.9)% (lignocaine), and 88(2.4)% (dobutamine), respectively: control v ligation, and lignocaine v ligation, p < 0.001; control v lignocaine, and dobutamine v ligation, p < 0.01. Stroke work at C0.4 decreased in the ligation group (63%, p < 0.001) and in the lignocaine group (70%, p < 0.001). CONCLUSIONS: When cardiac dysfunction is already present, decreased arterial distensibility has a further deleterious effect on cardiac output. This may be due to the fact that the pressure at the end of ejection is higher and as a result the change in dimension during ejection is considerably reduced, especially in cases with depressed cardiac function caused by afterload dependency. PMID- 8472270 TI - Cardiac transplantation affects ventricular expression of brain natriuretic peptide. AB - OBJECTIVE: The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. METHODS: Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant recipients from 1-74 weeks after transplantation. Right ventricular specimens (n = 10) were also obtained from normal hearts during necropsy as controls. RESULTS: Mean ventricular BNP in cardiac transplant recipients was higher (p < 0.05) than in normal hearts, at 13531(SEM 2244) pg.mg-1 soluble protein (range 3232-109448) v 56(11) pg.mg-1 (range 16-91). Ventricular BNP and ANP values were correlated (r = 0.57, p < 0.05). Plasma BNP concentrations were higher (p < 0.05) than plasma ANP concentrations, at 202(16) pg.ml-1 (range 84-655) v 100(12) pg.ml-1 (range 8 484), and were raised (p < 0.05) in comparison with normal plasma BNP concentrations of 20(1.8) pg.ml-1 (range 10-23). Mean ventricular BNP was correlated with time after transplant (r = 0.72, p < 0.05, n = 68) and with mean plasma BNP (r = 0.80, p < 0.05, n = 14). There was no significant relationship between BNP levels and intracardiac or systemic blood pressure, or prednisolone dose (0.1-0.3 mg.kg-1.d-1). The increase in ventricular BNP with time after transplant was not explained by cardiac rejection assessed from histology, and plasma BNP was not significantly increased during rejection episodes. CONCLUSIONS: High levels of BNP are synthesised and secreted by the transplanted human ventricle, and the transplanted ventricle may be an important source of circulating BNP. The significant positive association between ventricular BNP and time after transplant suggests a possible self compensatory mechanism or functional adaptation of the transplanted heart which may be beneficial to ventricular function. PMID- 8472271 TI - Relationship of abnormal intracellular calcium mobilisation to myocyte hypertrophy in human ventricular myocardium. AB - OBJECTIVE: Calcium transients in muscles from patients with end stage heart failure consist of two components (L1 and L2) at physiological extracellular calcium concentrations ([Ca2+]o); the second component (L2) can appear in normal human myocardium at high [Ca2+]o. In muscles from end stage heart failure patients L2 is associated with significant hypertrophy. To expand these observations a group of muscles from control patients with mild hypertrophy but without overt heart disease was studied (n = 8), in which a second calcium transient component was present during high [Ca2+]o. METHODS: Using the ratio of the two components of the calcium transient (L2/L1) seen in trabeculae from heart failure patients as a marker of intracellular calcium mobilisation, the hypothesis was tested that the extent of abnormality in transsarcolemmal calcium flux, and/or sarcoplasmic reticular calcium release and reuptake, correlates with the degree of hypertrophy present. RESULTS: In contrast to non-hypertrophied myocardium, hypertrophied myocardium from patients without heart failure often showed an increase in the L2/L1 ratio at higher [Ca2+]o. Hypertrophied myocardium from patients with failure showed a progressive increase in the L2/L1 ratio, reflecting further impairment of calcium mobilisation. There was a positive correlation between the degree of hypertrophy and calcium mobilisation alterations that was enhanced by raised [Ca2+]o. Altered [Ca2+]i mobilisation may develop early in the course of hypertrophy, before the onset of clinical signs of cardiac dysfunction. PMID- 8472272 TI - Impaired contraction and relaxation in skin resistance arteries from patients with congestive heart failure. AB - OBJECTIVE: The aim was to determine the pharmacological reactivity of human small resistance arteries in patients with cardiac failure. METHODS: Small arteries (< 300 microns internal diameter) were removed from gluteal skin biopsy specimens and mounted in a double myograph for isometric force recording. RESULTS: Arteries from six patients with congestive heart failure contracted to only 65% of the maximum response recorded in nine arteries from normal volunteers when activated by potassium chloride (124 mM), noradrenaline (1 microM), or both. The lesser contraction in congestive heart failure vessels with no significant shift in sensitivity (EC50) was also observed in concentration-response studies with noradrenaline, angiotensin I, and angiotensin II. The concentration-contraction curves for serotonin showed only 40% of the maximum contractility to K+ in normal arteries, and this ratio was similar in congestive heart failure arteries. Normal arteries precontracted with noradrenaline (1 microM) relaxed in response to sodium nitroprusside, calcitonin gene related peptide, and the endothelium dependent agonist acetylcholine; in congestive heart failure vessels there was a marked loss of the relaxation response only to acetylcholine. CONCLUSIONS: These results suggest that in chronic congestive heart failure skin resistance arteries have impaired contraction responses probably independent of any receptor down regulation. The loss of endothelium dependent vasodilatation to acetylcholine suggests that EDRF release is impaired. These changes may well play an important role in the disturbances of peripheral vascular function associated with heart failure. PMID- 8472273 TI - The left ventricle affects the duration of right ventricular ejection. AB - OBJECTIVE: The aim was to determine if rapid changes in left ventricular pressure can acutely alter right ventricular systolic pressure and thus influence the length of right ventricular ejection. METHODS: The experiments were performed in six open chest anaesthetised dogs, weight 18-25.5 kg. Left and right ventricular pressures and pulmonary blood flow were recorded continuously as left ventricular pressure was abruptly decreased by opening a shunt in systole. From these data, the pressure and flow changes and the duration of right ventricular ejection were determined. RESULTS: Opening the left ventricular shunt caused left ventricular pressure to fall from 94.1(SD 10.5) to 62.6(11.3) mm Hg (p < 0.01), right ventricular pressure to fall from 30.3(4.6) to 27.0(3.6) mm Hg (p < 0.01), and pulmonary flow to fall from 69.5(14.2) to 57.5(13.9) ml.s-1. The duration of right ventricular ejection, determined from pulmonary flow, also decreased from 192.7(22.7) to 157.2(18.7) ms (p < 0.05) and was significantly related to the length of left ventricular systole. Time between end diastole and peak negative dP/dt decreased for both left and right ventricle. Left and right ventricular time intervals were related before (r = 0.99) and after (r = 0.75) opening the shunt. CONCLUSIONS: The duration of right ventricular ejection was decreased by a sudden decrease in left ventricular afterload and was significantly related to the length of left ventricular systole. The duration of right ventricular ejection may be coupled with left ventricular contraction through ventricular interdependence. PMID- 8472274 TI - Kinetics of hydrolysis of cardiac S1 heavy chain isoforms and identification of light chain and actin binding sites. AB - OBJECTIVE: A comparative study of the kinetics of proteolysis of myosin S1 heavy chain was performed using dog ventricular and atrial S1 to distinguish between protease sensitive sites in S1 isotypes and to determine the binding sites on S1 heavy chain for LC1, LC2, and actin. METHODS: Digestion of S1 as a function of actin was performed at 25 degrees C at a trypsin to S1 ratio (w/w) of 1:1500. Myofibrils were digested (trypsin/myofibrils w/w ratio = 1:300) in the presence of ATP, ADP, and under rigor conditions. Light chain and actin binding sites were identified by the gel overlay method. RESULTS: Ventricular and atrial S1 were proteolysed at 0.13 min-1 and 0.04 min-1 respectively. Actin significantly reduced the cleavage rate of both S1 heavy chains by blocking hydrolysis at the 50/20 kD site. Myofibrillar myosin heavy chains from ventricles were also hydrolysed faster than those of the atria in the presence of 4 mM MgATP. The calculated rates were 0.42-0.50 and 0.17-0.19 min-1 for ventricular and atrial myofibrils respectively. MgADP 2 mM or absence of nucleotides reduced the cleavage rates to 0.04-0.07 (ventricular myofibrils) and 0.02-0.03 min-1 (atrial myofibrils) respectively. Gel overlay experiments showed that 125I labelled LC1 and LC2 bound to the 20 kD fragment and actin mainly to the 50 and 20 kD peptides. CONCLUSIONS: The 50/20 kD site in either ventricular or atrial S1 was blocked when actin was present, while proteolysis at the 25/50 site proceeded regardless of the presence of actin. However, the 25/50 site was less accessible to trypsin in the alpha myosin heavy chain, since the roughly threefold reduction in the rates of hydrolysis of atrial S1 heavy chain was also maintained in the myofibrils in rigor or in the presence of ADP. Although actin made contact with the 70 kD and the 25 kD fragments, the 50 kD and 20 kD fragments appeared to be the central "anchor" for binding of both light chains and actin. PMID- 8472275 TI - Cardiovascular responses to intrathecal dopamine receptor agonists after spinal transection in conscious rats. AB - OBJECTIVE: The cardiovascular responses to transient intrathecal administration of dopamine agonists were studied daily in chronically prepared rats that had been spinally transected or were sham operated. The goals were (1) to determine the group differences in evoked heart rate and arterial pressure responses and (2) to determine, within the transected group, whether or not the long term responses could be dissociated. The hypothesis tested is that cord transection releases a tonic inhibition of cardiovascular responsiveness independently of the mechanism of receptor hypersensitivity. METHODS: Changes in mean aortic blood pressure and heart rate induced by intrathecal administration of the mixed D1/D2 dopamine receptor agonist apomorphine (150 nmol per rat) were measured in conscious rats during a 10 d experimental period following spinal transection. RESULTS: Complete spinal transection did not affect aortic pressure but increased basal heart rate values by about 33% with respect to normal rats (p < 0.001). When apomorphine was injected caudally to the section (at T9-T10) but not rostrally (at T2-T4), it induced a 50% greater and an 800% more long lasting decrease in mean aortic pressure and a 230% greater and 70% more long lasting decrease in heart rate in spinal than in sham operated rats. These increases in cardiovascular responses were corroborated by a leftward shift of the apomorphine dose-response curves. They were also found after intrathecal administration of highly selective D1 and D2 receptor agonists fenoldopam (50 nmol per rat) and quinpirole (150 nmol per rat), and were specifically blocked by intrathecal haloperidol (27 nmol per rat), a non-selective dopamine antagonist. CONCLUSIONS: Complete spinal transection induces different increases in hypotensive and bradycardic responses to the stimulation of caudally located spinal dopamine receptors which could be due to the destruction of a tonically inhibiting spinal system rather than to hypersensitivity of the dopamine receptors. PMID- 8472276 TI - Lack of effect of propranolol on canine coronary collateral development during progressive coronary stenosis and occlusion. AB - OBJECTIVE: The aim was to test the effect of propranolol, a beta adrenergic receptor blocking drug which diminishes myocardial ischaemia, on coronary collateral development. METHODS: Dogs were chronically instrumented with a left circumflex coronary artery Doppler flow probe, ameroid constrictor, pneumatic occluder, and left atrial and aortic catheters. Haemodynamic studies and measurements of normal myocardial and collateral blood flows were performed at least weekly after surgery, or sooner if the left circumflex artery occluded spontaneously, in eight control dogs and seven animals treated with propranolol, 240 mg twice daily (a dose which successfully attenuated the chronotropic effect of a graded infusion of isoprenaline). In dogs in which the left circumflex artery occluded within the first four weeks after surgery, collateral blood flow was measured during exercise on a motorized treadmill. RESULTS: There was no difference between the groups in the rate or pattern of coronary collateral development, magnitude of collateral flow before or after spontaneous left circumflex occlusion, and collateral vascular reserve during exercise. At the time of coronary occlusion resting collateral flow was equivalent to normal perfusion levels in both groups and averaged 87-96% of normal flows during exercise. CONCLUSIONS: Propranolol has no observable effect on coronary collateral development despite its acknowledged ability to prevent or attenuate myocardial ischaemia. PMID- 8472277 TI - A numerical model of early diastolic filling: importance of intraventricular pressure wave propagation. AB - OBJECTIVE: The aim was to clarify the mechanism of the following observations: (1) left ventricular pressure recordings during diastole have shown that the minimum pressure at the base is greater than that at the apex; (2) echocardiographic measurements of the short axis dimension of the left ventricle during early filling have shown that the maximum rate of increase at the base occurs before that at mid-cavity. These observations cannot be explained on the basis of simple pressure-volume relationships and suggest that diastolic haemodynamics are more complex. METHODS: A numerical (computer) model of early diastolic filling was developed. The model represents the atrium and ventricle as distensible cylinders connected by a valve. Parameters in the model such as ventricular stiffness and rate and duration of relaxation can be varied and the resulting haemodynamic changes observed. RESULTS: Despite the simplicity of the model and the omission of several physiological variables, intracavity pressure gradients and the phase relation of radial wall movements are generated that appear to be similar to those found in the human heart. CONCLUSIONS: The results suggest that these observations can be explained by inflow causing a pressure disturbance at the base which propagates to the apex, and which is reflected back to the base. The time between peak rate of change of short axis dimension at the base and mid-cavity may thus be a practical way of assessing diastolic function independently of loading conditions. These values can easily be measured by M mode echocardiography. PMID- 8472279 TI - Direct myocardial effects of cocaine. AB - OBJECTIVE: The aim was to determine whether cocaine has a direct effect on the myocardium which is independent of coronary vasospasm. METHODS: Cocaine was introduced into the perfusate of the isolated rabbit ventricular septal preparation in the concentration range 10(-5) to 10(-3)M while holding coronary flow of oxygenated Krebs solution constant at 3.0 ml.min-1 by a perfusion pump. The septa were obtained from white male New Zealand rabbits and were paced at 48 beats.min-1. Mechanical and enzymatic measurements were performed. RESULTS: Developed tension (T), maximum contraction velocity (+dT/dt), and maximum relaxation velocity (-dT/dt) were all depressed to approximately the same degree at each different cocaine concentration and averaged 4, 48, and 95% at 10(-5), 10(-4), and 10(-3)M cocaine respectively, with an ED50 = 9 x 10(-5)M. Relaxation time (tR/T) was prolonged, but the ED50 was greater (by 1.5 times) than for the other mechanical parameters. Simultaneously, an increase in excitation threshold dysrhythmia developed which resulted in 17, 50, and 90 beats missed per 100 stimulations at 10(-5), 10(-4), and 10(-3)M cocaine respectively. Resting tension (RT) was not altered. Coronary flow rate was not reduced in presence of cocaine because of the constant delivery pump. T, +dT/dt, -dT/dt and modulation of the excitation threshold completely recovered after washout of cocaine. CONCLUSIONS: Cocaine has acute direct, though reversible, depressant effects on the myocardium, including depression of function and modulation of excitation threshold, which are independent of its effect on coronary flow. PMID- 8472278 TI - Negative inotropic and relaxant effects of cocaine on myopathic human ventricular myocardium and epicardial coronary arteries in vitro. AB - OBJECTIVE: Cocaine produces both vascular and myocardial effects that can lead to serious cardiovascular complications in man. Tissue catecholamine stores are known to be depleted in the advanced stages of heart failure. The effects of cocaine on cardiac and coronary smooth muscle isolated from patients with end stage heart failure was tested in order to evaluate the direct actions of this drug on human tissue. METHODS: Effects of cocaine HCl were studied on cardiac ventricular trabeculae carneae and epicardial coronary artery segments obtained at heart transplantation from patients with end stage heart failure. Muscles were placed in organ baths under physiological conditions for recording isometric tension; a subset of muscles was loaded intracellularly with the bioluminescent calcium indicator, aequorin. Cardiac muscles were stimulated with threshold pulses delivered via a punctate electrode at 0.33 Hz. Coronary segments were studied under basal conditions and after contraction with 60 mM KCl. RESULTS: In both cardiac muscle and vascular smooth muscle preparations, cocaine (10(-6)-10( 3) M) produced dose related negative inotropic and relaxant effects, respectively; positive inotropic actions and vasoconstriction were not seen. In cardiac muscle, the negative inotropic actions were associated with a simultaneous decrease in peak intracellular calcium levels. In contrast, cocaine induced relaxation of potassium contracted vascular smooth muscle was not associated with a fall in peak intracellular calcium levels, a result consistent with decreased myofilament calcium responsiveness. CONCLUSIONS: These results indicate that the depressant effects of cocaine on cardiac versus vascular smooth muscle occur by different mechanisms and suggest the need for specific therapeutic approaches to managing cardiac depression versus vasodilation when these occur in cocaine intoxicated patients. PMID- 8472280 TI - Effects of coronary blood flow on myocardial grey level amplitude in two dimensional echocardiography: an experimental study. AB - OBJECTIVE: The aims were: (1) to evaluate whether differences in absolute and cyclic echocardiographic image amplitude exist in different layers (subendocardium and subepicardium) and regions (septal, anterior, lateral, inferior wall) of the canine left ventricle; (2) to assess the dependence of these variables upon local variations of coronary blood flow. METHODS: In six anaesthetised open chest dogs the circumflex coronary artery was cannulated and perfused by a roller pump with blood from their own femoral artery. Maximum coronary vasodilatation was obtained by continuous adenosine infusion. The absolute values and the transmural distribution of coronary blood flow were measured by radionuclide labelled microspheres. Echo images were obtained in short axis view by a commercially available electronic sector scanner with a 5.0 MHz transducer directly placed on the epicardial surface of the right ventricle, and digitised off-line into a matrix of 256 x 256 pixels with 25% grey level per pixel. The average grey level was calculated for each region of interest. RESULTS: In 32 different conditions, circumflex flow ranged from 0.80 to 12.89 ml.min-1.g-1 and the endocardial/epicardial ratio of flow from 0.53 to 1.73. In the circumflex region (subjected to flow changes) segmental amplitude varied from 76(SD 20) (end diastole) to 56(18) (end systole), p < 0.001. In all regions, a consistent cyclic variation was found, ranging from 9(14) to 28(16)%. For all levels of flow, subendocardial and subepicardial regions showed similar values of both absolute amplitude and cyclic variation. No significant relationship was found between transmural distribution of blood flow and either segmental amplitude (r = 0.26) or cyclic variation (r = 0.04). CONCLUSIONS: (1) a consistent cyclic grey level variation is present in all regions of the canine left ventricle, but subendocardial and subepicardial layers show similar values of both absolute amplitude and cyclic variation; (2) in the absence of severe underperfusion and echocardiographically detectable dyssynergy, absolute amplitude and cyclic variation are totally unrelated to changes in coronary blood flow. PMID- 8472281 TI - Three dimensional visualisation of velocity profiles in the normal porcine pulmonary trunk. AB - OBJECTIVE: The aim was to obtain detailed data of velocity profile development in the porcine pulmonary trunk. METHODS: Hot film anemometry was used for point blood velocity measurements in the entire cross sectional area one diameter downstream of the normal porcine pulmonary valve. Computerised three dimensional visualisations of the spatial and temporal development of blood velocity profiles were made. Measurement series were conducted under spontaneous and stressed haemodynamic conditions in 16 pigs with a body weight of approximately 90 kg. RESULTS: The velocity profiles revealed consistent temporal and spatial development characteristics. In the systolic acceleration phase the profile was flat, but during peak systole an initially counterclockwise rotation was seen; subsequently the profile turned clockwise and ultimately counterclockwise to become flat during early and late systolic deceleration phases. CONCLUSIONS: These skewed, rotating velocity profiles are in conflict with the generally accepted assumption that the velocity profile in the pulmonary trunk is flat. The rotating skewness of the velocity profile in the porcine pulmonary trunk has not been described before. The reason for the rotating velocity profile is obscure. PMID- 8472283 TI - Contractile properties of isolated porcine ventricular myocytes. AB - OBJECTIVE: The aim was to examine the structure, function, and inotropic responsiveness of isolated porcine myocytes. METHODS: Left ventricular myocytes were harvested from six pigs with normal echocardiographic and pressure indices of left ventricular function: fractional shortening 30 (SEM 2)%, peak+dP/dt 1225(110) mm Hg.s-1, end diastolic pressure 7(2) mm Hg, and cardiac output 2.8(0.5) litres.min-1. Indices of myocyte contractility were examined using a computer assisted video edge detection system which included the percent and velocity of myocyte shortening. Myocyte contractions were recorded by alternating field stimulation at 1 Hz and measurements performed in the presence of 2-10 mM extracellular Ca2+. Contractile properties of isolated porcine myocytes were examined unattached (n = 20) or following attachment to a basement membrane substrate (n = 63). RESULTS: Left ventricular myocytes were successfully obtained from all pigs with a 68% average yield of viable myocytes. Isolated myocyte length was 128(6) microns with an average profile surface area of 2226(51) microns 2 (coefficients of variation of 25% and 35% respectively). Electron microscopic examination showed normal cytoarchitecture with 62(4)% myofibrils by volume. Baseline extent and velocity of shortening for unattached myocytes was 6.2% and 77(10) microns.s-1 respectively. Baseline extent and velocity of shortening for myocytes adherent to a basement substrate were 4.9(0.4)% and 64(7) microns.s-1. These indices of myocyte contractile function increased from baseline values for both the unattached and attached cells with increased extracellular Ca2+. CONCLUSIONS: Isolated porcine left ventricular myocytes retain normal cytoarchitecture and composition, respond to field stimulation, and are responsive to extracellular Ca2+. Myocytes adherent to a basement membrane substrate were capable of contracting against this resistive load. PMID- 8472282 TI - Influence of hyperkalaemia and ischaemia on non-receptor-mediated cardiac electrophysiological effects of naloxone. AB - OBJECTIVE: The aim was to investigate the cardiac electrophysiological effects of the opioid receptor antagonist naloxone and examine whether hyperkalaemia and ischaemia influence these effects. METHODS: The cardiac electrophysiological effects of racemic naloxone, nalmafene, and morphine were examined in superfused rabbit papillary muscles under normal conditions and in the case of naloxone under conditions of hyperkalaemia. The electrophysiological effects of racemic naloxone and d-naloxone were examined in arterially perfused rabbit interventricular septa before and during 30 min global zero flow ischaemia; the rate of rise of extracellular K+ concentration was also measured. RESULTS: Naloxone, nalmafene and morphine all prolonged action potential duration and effective refractory period in superfused papillary muscles (class III effects), suggesting that these effects are not receptor mediated. During hyperkalaemia, naloxone increased the depressant effect on the maximum upstroke velocity of the action potential and enhanced post-repolarisation refractoriness, further suggesting a class I effect. Both racemic naloxone (active at opioid receptors) and d-naloxone (inactive) prolonged action potential duration and effective refractory period in septa, again suggesting non-receptor-mediated effects. During myocardial ischaemia the class III effects of both compounds were gradually lost in such a way that post-repolarisation refractoriness developed. Both compounds reduced the rate of rise of extracellular K+ concentration and preserved resting membrane potential, but the fall in maximum upstroke velocity was enhanced, again suggesting that naloxone has an additional class I effect in partially depolarised ventricular myocardium. CONCLUSIONS: The antiarrhythmic activity of naloxone in models of myocardial ischaemia/reperfusion can be explained by non-opioid receptor mediated effects on the duration and maximum upstroke velocity of the action potential and on extracellular potassium accumulation during ischaemia. PMID- 8472284 TI - Ischaemia and reperfusion induced transient QRS vector changes: relationship to size of the ischaemic territory. AB - OBJECTIVE: The aim was to investigate QRS vector changes during the first 30 min of coronary occlusion or the early phase of reperfusion with special reference to location and size of myocardium at risk. METHODS: 24 h experiments were performed in closed chest anaesthetised pigs. QRS vectors were studied by computerised vectorcardiography via Frank leads. Occlusion of the left anterior descending coronary artery followed by reperfusion was induced in 23 pigs and a sustained occlusion in 20 pigs: left anterior descending coronary artery in seven, right coronary artery in eight, and left circumflex coronary artery in five. Myocardium at risk was measured in postmortem autoradiograms. Eight animals were excluded. RESULTS: Four minutes after occlusion, QRS(mean) deviated towards the ischaemic region in 34/35 animals and returned thereafter at varying speeds. In half of the reperfused animals, deviation of QRS vectors towards the ischaemic territory was also observed during the first minutes of reperfusion. A paradoxical increase in QRS vector changes, "reperfusion peak", was recorded during the initial minutes of reperfusion in 12/19 animals. Maximum spatial QRS vector magnitude increased in all right coronary or left circumflex coronary occlusion animals compared to 6/25 in left anterior descending coronary occlusion animals. QRS vector difference, change in spatial QRS vector angle, and maximum change in QRS azimuth 4 min after occlusion correlated significantly with extent of myocardium at risk. CONCLUSIONS: Marked directional and quantitative QRS vector changes, with significant relation to size and location of myocardium at risk, were recorded during the initial minutes of ischaemia. The transient increase in QRS vector changes during the first minutes of reperfusion deserves further exploration as a new indicator of reperfusion. PMID- 8472286 TI - [Smoking and the development of lung cancer]. AB - It is generally accepted that cigarette smoking is the most important lung cancer risk factor to which 80-90% of lung cancer mortality in advanced countries with a high tobacco consumption is ascribed. In the Czech Republic the increase of tobacco consumption since the end of the Second World War was arrested at the end of the sixties. Since the beginning of the seventies the cigarette consumption did not change substantially and varied close to 2500 cigarettes per inhabitant above 15 years. No reliable data are so far available in the Czech Republic on the development of the prevalence of smoking in different age groups of the population. According to several non-representative surveys in different districts it may be assumed that in men aged 25-64 years in the course of the last 20 years the ratio of male smokers declined probably, while it increased in female smokers. Due to the long "latency" between exposure to noxious substances and the manifestation of lung cancer which amounts to two, three or more decades, we have to evaluate the present mortality rate from lung cancer as a reflection of carcinogenic factors (above all cigarette smoking) in the more remote past. When evaluating the trend of mortality from lung cancer in the Czech Republic during 1953-1989, throughout that period the values were much higher in men that in women and the trend in the two sexes was quite different. In men the mortality rate from lung cancer increased in 1953-1967 to three times the initial value, while in women the levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472285 TI - Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs. AB - OBJECTIVE: The aim was to investigate the role of local formation of angiotensin II and bradykinin in the reduction of myocardial infarct size. METHODS: Bilaterally nephrectomised male mongrel dogs were used. Effects were compared of pretreatment with three inhibitors of angiotensin II forming enzyme-captopril (an angiotensin converting enzyme inhibitor), nafamostat (a serine protease inhibitor), and chymostatin (a cysteine protease inhibitor)--on left anterior descending coronary artery occlusion. Haemodynamic variables were monitored and blood was collected from the anterior interventricular vein and the aorta. Angiotensin I, angiotensin II, and bradykinin were measured by radioimmunoassay. After 90 min of occlusion, infarct sizes were determined by a macroscopic enzyme technique. RESULTS: Angiotensin II release into the anterior interventricular vein increased from 0.03(SEM 1.19) pg.min-1 (before coronary occlusion) to 4.64(1.37) pg.min-1 (n = 14, p < 0.05), while angiotensin I release and plasma renin activity remained unchanged. The increase in angiotensin II release was inhibited by nafamostat and chymostatin, but not by captopril. Bradykinin release increased from -3.18(2.72) (before coronary occlusion) to 34.7(12.3) pg.min-1 (n = 14 p < 0.05) by 30 min after occlusion. This increase was augmented by captopril, from 4.10(2.86) before occlusion to 97.8(39.6) pg.min-1 at 5 min after occlusion (n = 12, p < 0.05), but not by nafamostat or chymostatin. Infarct size was smaller (p < 0.05) in the captopril group than in the control group. CONCLUSIONS: Angiotensin II is locally produced in the ischaemic heart by both serine protease(s) and chymostatin inhibitable protease(s), but not by angiotensin converting enzyme. From the reduction in myocardial infarct size produced by angiotensin converting enzyme inhibition, it seems that bradykinin accumulation may play a more important role than the suppression of angiotensin II formation. PMID- 8472287 TI - [Prevalence of bronchial asthma, chronic bronchitis and bronchial hyperreactivity in the adult population in the Prague 8 district]. AB - The prevalence was assessed in a randomized group of 18-year-old and older inhabitants of Prague 8. A total of 8458 internationally tested questionnaires were sent out to a population of 90,458; information was obtained on 7605 (89.9%), 1274 were given a detailed examination by standardized methods. Cumulative prevalence of bronchial asthma (B): 2.3% +/- 0.3% (same in M and F). The highest values at the age of 18-20 years were 3.5%; 3.6% in the age group 21 30 years, the absolutely highest values--4.6%--were recorded in 18-year-old men. Contemporary prevalence of BA: 1.99%. In BA bronchial obstructions were found in 51%, bronchial hyperreactivity in 75%, positive skin tests in 71%, an increase of IgE in 36%. Prevalence of chronic bronchitis (CHB): 14.1%; men 17.6% women- 11.3%, highest value--18.9%--in the age group 70-80 years; absolutely highest values were recorded in men aged 70-80 years--20.9%. In CHB there was a bronchial obstruction in 55% and this obstruction was reversible in 40%. In the group CHB bronchial asthma was recorded in 20%. Prevalence of bronchial hyperreactivity (BHR) was estimated from results of broncho-provocative tests and from the calculation according to prevalence of BHR in respiratory diseases. The thus calculated figure was 13.7%. The incidence of bronchial asthma in chronic bronchitis in 1/6 and of bronchial hyperreactivity in more than 1/10 of the adult population are striking facts. It is essential to find the causes of these findings and make effective provisions to counteract them. PMID- 8472288 TI - [Immunologic laboratory findings in relatives of patients with common variable immunodeficiency]. AB - A statistically significant increase of selective IgA deficiency was found evaluating 52 first degree relatives of 15 patients with common variable immunodeficiency, 4/5 of these cases were observed in the children of our patients. In addition to this decreased mean serum IgM level and increase of frequency of antithyroid autoantibodies compared to control subjects were observed. An excess of rheumatoid factor or antinuclear antibodies as not observed. PMID- 8472289 TI - [New advances in dermatology in the USA]. PMID- 8472290 TI - [Why do we make mistakes in identifying risk patients?]. AB - Risk stratification studies, which are aimed at early identification of patients at high risk of clinical complications, are based on comparatively complex techniques for the analysis of retrospectively collected clinical data. Many of these studies contain serious misconceptions and errors in their analysis. This paper is a methodological review which lists the most frequent errors and omissions in retrospective stratification studies. The paper explains the principle of receiver operator characteristics and positive and negative predictive accuracy, and demonstrates the necessity of using a representative patient population for risk stratification. The danger of misleading conclusions resulting from a multivariate analysis, and several suggestions on how to organise and evaluate these studies are also discussed. PMID- 8472291 TI - [Ultraviolet rays and their biological effects]. AB - In conjunction with contamination of the atmosphere by freons interest in geophysical and health aspects of "ozone holes"--seasonal incidence of increased intensity of UV radiation--is increasing. Its biological effects depend on the intensity, period of exposure and wavelength. There is a wide range of different damage, local as well as general. In addition to pigmentation of the skin and symptoms produced by an elevated histamine blood level we find also changes which may have more serious and permanent consequences. These changes include the number and structure of Langerhans islets, changes of the peripheral capillary walls, dimerization of pyrimidine and thymine in DNA. These changes contribute to the development of malignancies of the skin. After exposure of the eye changes of pigmentation are found, and depending on the dose, also development of conjunctivitis or retinal damage. Recently interaction of UV radiation with arsenic was investigated. Conversely therapeutic effects of UV radiation in combination with chemotherapy are used in dermatology, such as inhibition of contact sensitization. PMID- 8472292 TI - [The clinical picture of biocompatibility of intraocular lenses used in cataract surgery]. AB - Implantation of a synthetic prosthesis of a turbid lens is associated with a defined reaction of intraocular tissues. The extent of tissue damage along with a disorder of the haemato-ocular barrier and properties of the implant determine the extent of the inflammatory reaction leading to accumulation of proteins and cells in the anterior chamber of the eye and on the anterior surface of the artificial lens. The intensity of this reaction has an impact also on the final functional effect of the operation. PMID- 8472293 TI - [Diagnosis of primary hyperlipoproteinemia during a preventive examination]. AB - The study analyses the occurrence and etiology of hyperlipoproteinemia (HLP) in healthy middle-aged probands who participated in a preventive examination. Frequency of HLP was 35%. After a 2-month low-cholesterol-diet, a control biochemical examination was done. The concentration of serum triglycerides decreased significantly (3.02 +/- 1.47, 2.02 +/- 1.14, p < 0.05, respectively). The occurrence of type IV HLP decreased from 51.6% to 24.4% (p < 0.003). For the analysis of etiology of HLP we divided the hyperlipemic probands on the basis of presence of normolipemy (I. group), or HLP (II. group) in the control, and compared the lipid levels between them. We found out that the cholesterol levels in the II. group were significantly higher than in the I. group already before the diet-period (7.0 +/- 0.87 mmol/l, 5.85 +/- 0.81 respectively, p < 0.001), although the both groups did not differ in the triglyceride levels. Genetic examination in families revealed familial combined HLP in 24.4%, primary hypercholesterolemia in 12%, familial hypertriglyceridemia in 2% polygenic hypertriglyceridemia in 18%. We found out not only very high incidence of HLP in a sample of Slovak population but also that the most cases have the genetic background. The most frequent type of HLP was type IV. Since the triglyceride levels give poor information about the coronary risk, we recommend to examine the HDL-cholesterol already in the screening preventive programs. PMID- 8472294 TI - [Disorders of the acid-base equilibrium in delirium tremens]. AB - The objective of the present work was to assess the most frequent disorder of the acid-base equilibrium in delirium tremens. The author examined a group of 77 alcoholics with delirium tremens. In 62 (80.5%) by the Astrup method respiratory alkalosis was detected, in 7 (9%) metabolic alkalosis was recorded, in 1 (1.5%) metabolic acidosis and in 7 patients (9%) the values of the acid-base equilibrium were normal. In predominant alkalotic syndrome the mean serum potassium level was lower, 3.4 mmol/l (2.2-4.6), and the level of chlorides 97.8 mmol/l (50-144.5). The mean sodium concentration was 138.1 mmol/l (121.5 to 147). The author discusses the causes of the impaired acid-base balance in delirium tremens. It is assumed that the main cause is the rebound phenomenon of the respiratory centre which causes hyperventilation and changes of the ion metabolisms induced by alcohol abuse and its discontinuation. A negative effect is exerted by shortage of energy substrates and protein catabolism the effect of ethyl alcohol on the intermediary metabolism, the psychosis as such, insufficiency of parenchymatous organs and neurohumoral dysregulation after discontinued alcohol intake. Examination of the acid-base equilibrium in delirium tremens is essential for differential diagnosis, correct treatment and prevention of complications. The author discusses briefly treatment of delirium tremens and principles of correction of associated acid-base and ion disorders. PMID- 8472295 TI - [The importance of recombination in resolving paternity disputes]. AB - For evaluation of the results of HLA examinations in paternity disputes the objective finding that the man has HLA antigens which the child inherited from the father, is decisive. The controversy as regards heredity ensuing from assessment of HLA haplotypes of the man by family studies is caused by recombination. The author presents a case of this type. PMID- 8472296 TI - [Report on the activities of the Central Commission on Ethics of the Czech Ministry of Health 1990-1992]. AB - The central ethical commission (CEC) of the Czech Ministry of Health was founded in 1990. The authors submit a report on the activities of this advisory and expert in the sphere of medical ethics. They emphasize that a standpoint was elaborated regarding the problem of doping in the Czech Republic, a moral code of patients' rights and other important documents. The CEC takes into account also views of chairmen of local ethical commissions which were assembled by means of a questionnaire. The CEC foresee its future activity in particular in adequate presentation of its views to the professional and lay public. PMID- 8472297 TI - [Paracelsus (1493-1541) and his legacy to our time]. PMID- 8472298 TI - Improvements for the anatomical characterization of insect neurons in whole mount: the use of cyanine-derived fluorophores and laser scanning confocal microscopy. AB - The optical sectioning capability of the laser scanning confocal microscope was utilized to image dye-filled neurons within whole-mounted insect ganglia. Specific pterothoracic interneurons, in the moth Manduca sexta, were retrogradely filled with Neurobiotin and subsequently visualized with a monoclonal anti-biotin conjugated with one of the following fluorophores: fluorescein, and the newly developed cyanines, Cy3.18 (Cy3) and Cy5.18 (Cy5). Overall, the Cy5 fluorophore was best suited for imaging insect neurons within ganglia. This new methodology allowed us to identify and characterize morphologically a collection of descending multisegmental interneurons with large or small diameter somata. A variety of larger molecular weight (10,000 daltons) tracers was also used to examine the possibility of nonselective filling of neurons with Neurobiotin, possibly through gap junctions. We also investigated the usefulness of Cy3 and Cy5 as fluorophores for transmitter immunostaining of neurons in whole mount. Neurons immunoreactive for serotonin and the neuropeptides, FMRFamide and SCPB, were imaged in the brain and the pterothoracic ganglion. The central projections of some of these immunoreactive neurons were imaged in their entirety. PMID- 8472299 TI - Selective binding and transcytosis of latex microspheres by rabbit intestinal M cells. AB - The interaction between polystyrene microspheres and the follicle-associated epithelium of rabbit Peyer's patches has been examined. Microspheres bind selectively to, and are transcytosed by, membranous or microfold (M) cells within the follicle-associated epithelium. M cells are able to transport, in 45 min, approximately 10(5) microspheres of 0.46 micron diameter across the epithelium overlying each lymphoid follicle dome of rabbit Peyer's patches. The high capacity of M cells for particulate transcytosis and the subsequent delivery of these particulates to the mucosal immune system highlights the potential importance of this portal in the delivery of antigens and drugs. In addition, the selective binding and uptake of microspheres may be utilised as a functional marker in the identification and isolation of M cells. PMID- 8472300 TI - Aggregation of macrophages in the tips of intestinal villi in guinea pigs: their possible role in the phagocytosis of effete epithelial cells. AB - Numerous macrophages were found aggregated in the lamina propria at the tips of villi in the small intestine of guinea pigs. These macrophages extended their pseudopodia into the epithelial lining and internalized fragments of effete enterocytes in their phagosomes. The epithelium of the villus tips was found to be infiltrated with numerous lymphocytes. They possessed electron-dense granules characteristic of natural killer cells, and actively interdigitated with the enterocytes. The latter were either fragmented or extensively lost in their basal cytoplasm, often leaving an attenuated apical cytoplasm of the cell. Immunohistochemical labeling using bromodeoxyuridine demonstrated that at 96 h after its administration, immunolabeled nuclei were encountered in the cytoplasm of macrophages in the lamina propria at the villus tips. These findings suggest that in the guinea pig, effete enterocytes are not simply exfoliated into the lumen, but are damaged by intraepithelial lymphocytes possessing a natural killer cytotoxicity, and subsequently phagocytosed by subepithelial macrophages. PMID- 8472301 TI - The Leydig cell of the human testis--a new member of the diffuse neuroendocrine system. AB - A number of marker substances for neuronal and neuroendocrine cells have been demonstrated in the cytoplasm of the interstitial Leydig cells of human testes using basic immunocytochemical methods and some of their modifications. We were able to reveal immunoreactivity for enzymes involved in the synthesis of the catecholamines dopamine and noradrenaline (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase), for the indolamine 5 hydroxytryptamine (serotonin), as well as for a number of well-known neuronal markers such as the neurofilament protein 200, synaptophysin, chromogranin A + B, the neural cell-adhesion molecule (N-CAM), the microtubule-associated protein (MAP-2), and the calcium-binding proteins: S-100, calbindin and parvalbumin. Immunoreactivity for these substances was found in the majority of the interstitial cells although differences in the staining intensity among the individual Leydig cells and among Leydig cells from different patients were observed. At the electron-microscopic level the Leydig cell cytoplasm was seen to contain microtubules, intermediate- and microfilaments as well as clear (40-60 nm) and dense-core (100-300 nm) vesicles, providing a morphological correlate for some of the immunocytochemical results. Although individual marker substances are not absolutely specific for nerve and neuroendocrine cells, the results obtained, together with the already established neuron-specific enolase-, substance P-, methionine-enkephalin- and proopiomelanocortin (POMC)-derived peptide-like immunoreactivity, provide strong evidence for the neuroendocrine (paraneuronal, APUD-like) nature of the Leydig cells of the human testis. PMID- 8472302 TI - Immuno-electron microscopic localization of calmodulin and calmodulin-binding proteins in the mouse germ cells during spermatogenesis and maturation. AB - When extracts of mouse testis were Western-blotted against a monoclonal antibody which reacts with calmodulin in the presence of Ca2+, all calmodulin was associated with the macromolecules of molecular weight above 50 kDa. Immuno electron microscopy of testes using this antibody indicated that calmodulin is localized at higher density in the nucleus and cytoplasm of germ cells during the developmental phase between pachytene and round spermatid, showing the highest level just before meiotic divisions. There was no special association of calmodulin to any organelles in these cells. Extremely low levels of calmodulin occurred in spermatogonia and other testicular tissue cells. Calmodulin decreased dramatically as spermatids underwent metamorphosis, becoming detectable only at the perinuclear space of sperm heads. Further relocation to the postacrosomal region occurred during sperm transit to the cauda epididymis. Immunodetection after the calmodulin overlay on ultrathin sections revealed a sharp increase of calmodulin immunogold deposits in the nuclei of spermatids accompanying their condensation. The results indicate that some calmodulin-binding proteins, but not calmodulin itself, accumulate in the nuclei during the final steps of spermiogenesis. PMID- 8472304 TI - Morphological observations on the unique paired capillaries of the opossum retina. AB - Light-microscopic and ultrastructural analysis of the ocular tissues of the North American opossum (Didelphis virginiana) revealed that the arterial and venous segments of retinal vessels, including capillaries of the smallest calibre, occur in pairs. They do not form anastomotic networks, the common pattern in mammals with vascularised retinae, but instead the two segments of the pair join to form hairpin end loops. The paired vessels, with the arteriolar limb usually on the vitread aspect, penetrate the retina and branch to form three distinct layers of capillaries. The most superficial lies in the nerve fiber layer, the middle is situated in the inner nuclear layer and the deepest extends to the external limiting membrane, which is considerably deeper than in normal mammalian holangiotic retinae. The paired capillaries display classical morphological features of central nervous system capillaries, i.e., they are lined by continuous endothelial cells united by tight junctions. The lining endothelium is supported by a distinct basal lamina that splits to envelop pericytes. The latter, although abundant, are invariably interposed between the two vessels that form each vascular unit. Phylogenetic and functional aspects of this unique form of retinal vascularisation are discussed. PMID- 8472303 TI - Bone-like nodules formed in vitro by rat periodontal ligament cells. AB - The periodontal ligament has been shown to possess the ability to regenerate both new cementum and alveolar bone as well as a self-regenerative capacity; however, the source of cementoblasts and osteoblasts is not still clear. We investigated the development of bone-like tissue in vitro by periodontal ligament cells, in order to determine whether the periodontal ligament contains osteoprogenitor cells. Periodontal ligament cells were obtained from periodontal ligament tissue attached to the maxillary incisors of 6-week-old WKA rats by means of the explant technique. Cells at passage #3 were cultured for long term in alpha-minimum essential medium containing 10% fetal bovine serum, antibiotics, and 50 micrograms/ml ascorbic acid, and were then examined using phase-contrast microscopy, histochemistry, transmission electron microscopy, X-ray microanalysis, and electron diffraction. Nodules were formed in the cultures, and when 10 mM Na-beta-glycerophosphate was added, these nodules became mineralized. The mineralized nodules were identified as bone-like elements in view of the presence of osteoblast-like and osteocyte-like cells, collagenous matrix, a mineral composed of hydroxyapatite, and intense alkaline phosphatase activity. The results show that the periodontal ligament contains osteoprogenitor cells, which differentiate into osteoblasts and produce bone-like tissue. PMID- 8472305 TI - Computer-assisted morphometry of the intracapillary leukocyte pool in the rabbit lung. AB - Computer-assisted morphometry was performed to evaluate the number and cell characteristics of capillary and alveolar leukocytes in rabbit lungs. An image processing system and a programmable spread-sheet program were used, which allowed morphometric analysis of a large reference area. Neutrophils represented the largest intracapillary leukocyte population (2.2 x 10(7)/ml parenchyma, which corresponds to an approximately 104-fold microvascular enrichment of this cell type related to cell counts calculated for the capillary blood volume). In addition, large numbers of intracapillary lymphocytes (1.7 x 10(7)/ml parenchyma; 47-fold enrichment) and monocytes (0.3 x 10(7)/ml parenchyma; 86-fold enrichment) were detected. The total count of pulmonary leukocytes thus approximated the total number of pulmonary endothelial cells; and the total circulating pools of the different leukocytes were surpassed by the corresponding lung capillary pools, 3.2-fold for neutrophils, 1.2-fold for lymphocytes and 4.8-fold for monocytes. In contrast, alveolar cell numbers ranged from 1-2% of the capillary counts for all types of leukocytes. We conclude that the rabbit lung microvasculature harbours large pools of immunocompetent cells, which may contribute to host-defense mechanisms at the gas-exchange area. PMID- 8472306 TI - Localization and production of immunoreactive endothelin-1 in the trophoblast of human placenta. AB - Regarding their endocrine and paracrine activities, endothelins can be considered as peptide hormones and growth factors. The presence of endothelin-1 (ET-1) binding sites on smooth muscle of placental villous vessels, on villous trophoblast and on purified trophoblast in culture raises the question of the origin of the peptide. In placenta, endothelin could derive from maternal, fetal and/or endogenous sources. Therefore, localization of ET-1 was investigated by use of immunohistochemistry in human term placenta and in cultured trophoblast using the avidin-biotin-peroxidase complex procedure. Specificity of immunostaining was demonstrated by applying ET-1 antibody that has been preabsorbed with excess peptide. In sections of placenta, ET-1 immunoreactivity (ET-1 IR) was specifically detected in the endothelium of the vessels and in the syncytiotrophoblast of the villi. ET-1 IR was also detected in the decidua-like cells and in the extravillous cytotrophoblast of the basal plate, a region where the maternal and fetal cells intermingle closely. The extravillous cytotrophoblast of the chorionic plate and of the placental septa also exhibited a strong ET-1 IR. For trophoblast culture cytotrophoblastic cells were obtained from placental villi by trypsin-DNase dispersion, further purified on Percoll gradient and enriched by employing a monoclonal anti-HLA class-I antibody. The trophoblastic origin of the cells was demonstrated by immunohistochemistry and by studying the secretion of gestational hormones during culture. After different periods of culture of purified cytotrophoblastic cells (1 to 5 days), ET-1 IR was observed in 95% of cells: cytotrophoblastic cells, trophoblast aggregates, and syncytiotrophoblast.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472307 TI - Cells isolated from the endosteal bone surface of adult rats express differentiated osteoblastic characteristics in vitro. AB - Endosteal bone surface cells were previously shown to be involved in the regulation of bone formation in humans. In this study, we have characterized the cells isolated from the endosteal bone surface in adult rats. Fragments of periosteum-free tibia were obtained from 4-, 6- and 9-month-old rats by collagenase digestion, and the phenotypic characteristics of the osteoblastic cells migrating from the endosteal bone surface were evaluated in culture. Endosteal bone surface cells present a strong alkaline phosphatase (ALP) activity as shown by cytochemistry and measured biochemically. The cells synthesize high levels of osteocalcin as measured by radioimmunoassay. Osteocalcin production was increased after stimulation with 10 nM 1,25 dihydroxyvitamin D (1,25(OH)2 D) and the response to 1,25(OH)2 D was similar at all ages. Endosteal cells from young adult rats (4 months old) but not from older rats (6 and 9 months old) showed increased cAMP production in response to 10 nM parathyroid hormone (PTH), suggesting an age-related decrease in the PTH-responsiveness of the bone surface cells. Immunocytochemistry using specific antibodies showed that preconfluent endosteal bone cells from adult rats expressed collagen and noncollagenous bone proteins in culture in the absence of inducers. The cells synthesized mostly type I collagen which remained localized intracellularly. Type-III collagen was only expressed at low levels. The bone surface cells also expressed osteocalcin and bone sialoprotein, two markers of differentiated osteoblasts, as well as osteonectin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472308 TI - Effect of mechanical stimulation on the production of soluble bone factors in cultured fetal mouse calvariae. AB - Mechanical stimulation by intermittent compressive force (ICF) stimulates bone formation and inhibits bone resorption in cultured fetal mouse bone. Fetal bone tissue can produce autocrine factors that stimulate bone cell replication and matrix formation, and paracrine factors that increase the formation of osteoclast precursor-like cells from bone marrow. In the present study, we have tested whether ICF affects the production of such local factors in fetal mouse calvariae. Calvariae were cultured for 4 days in the presence and absence of ICF (130 mbar, 0.3 Hz). Conditioned medium was collected daily and pooled. We found that conditioned medium from ICF-exposed cultures stimulated [3H]-TdR incorporation into DNA, and [3H]-proline incorporation into collagenase digestible protein but not into non-collagen protein in fresh calvarial cultures. Treatment with conditioned medium from ICF-exposed cultures had earlier effects on [3H]-TdR and [3H]-proline incorporation than direct treatment with ICF. Conditioned medium from ICF-exposed cultures decreased the number of osteoclast precursor-like cells in bone marrow cultures stained for tartrate-resistant acid phosphatase. We conclude that ICF stimulates the release (activity) of an autocrine growth-factor from bone. In addition, ICF can stimulate the release (activity) of a paracrine factor, inhibiting the growth and/or differentiation of osteoclast precursor-like cells. These data suggest that mechanical forces may modulate skeletal (re)modeling by affecting the production of local growth factors. PMID- 8472310 TI - Cytotoxic ribonucleases and chimeras in cancer therapy. AB - Ribonucleases serve as cytotoxic agents during host defense and physiological cell death pathways. In bacteria, higher plants, and mammals, ribonucleases appear to bind cells, enter the cytosol where they degrade RNA, and kill the target cell. This process functions in interstrain competition in bacteria, in the death of incompatible pollen in higher plants, and likely plays a role in the antiparasitic and anticancer activity of eosinophils in man. One can alter the target cell specificity of RNases by coupling them to new cell-binding domains. Chemically coupling RNases to new binding moieties or fusing RNase genes to antibody genes results in chimeric molecules with specified cell-type cytotoxicity. Thus, one can target one's own host defense cytotoxins to select cell populations. This allows the use of human proteins, instead of plant and bacterial toxins, in the construction of immunotoxins. RNases also can be engineered to kill cells by cytosolic expression or to kill viruses by packaging into viruses. Engineering RNases into cell-type-specific cytotoxins may result in a new class of therapeutic reagents. We review a number of interesting physiological cell cytotoxicity pathways utilizing RNases and then describe the recent results on engineering RNases for therapeutic use. PMID- 8472311 TI - Therapeutic applications of anti-CD4 antibodies. AB - The CD4 molecule represents a major functional T-cell surface molecule, defining an important T-cell subset, which also is expressed on monocyte, dendritic, and Langerhans cells. Various in vivo studies have demonstrated its implication in various steps of physiological T-cell activation: 1. CD4 interacts with its physiological ligand, the class II molecules, thus increasing the affinity of the conjugation between CD4+CD(3+)-TCR+ and class II+ antigen-presenting cells. 2. Through CD4, the signal transduction machinery is stimulated via its association with p56lck. In addition, CD4 has proved to be the receptor for gp120, the surface glycoprotein of HIV, that allows the virus to penetrate the CD4+ T cells and monocytes. Based on in vitro studies in various animal models, CD4 mAbs have proved to be efficient in the prevention and/or therapy of a variety of immunologically based diseases: 1. When injected early in the prodromic phase of autoimmune diseases (AID) such as diabetes, either delay or prevention is achieved with or without maintenance after therapy. 2. These mAbs have proved to be self-tolerogenic, thus allowing prolonged in vivo therapy and suppression of immunogenicity of mAb of a distinct specificity. In humans, CD4 mAbs are, or could be, used and evaluated in AID (lupus, diabetes, rheumatoid arthritis, etc.), transplantation, leukemias and lymphomas expressing CD4, and, finally, in AIDS patients, in whom CD4 mAbs can block HIV-CD4 binding and deliver a negative signal to T cell, thus blocking T-cell activation and HIV transcription. CD4 mAbs at least provide evidence that the CD4 molecules are suitable for immunomodulation and could be the target for a new pharmacological antagonist. PMID- 8472309 TI - Irradiation-induced effects on the innervation of rat salivary glands: changes in enkephalin- and bombesin-like immunoreactivity in ganglionic cells and intraglandular nerve fibers. AB - When treating head and neck for cancer with the use of radiotherapy the salivary glands are usually within the treatment volume with ensuing dryness and discomfort. Since the autonomic nervous system is of pivotal importance for the salivary gland function and integrity, the irradiation-induced effects may involve an influence on the innervation of salivary glands. Therefore, the rat submandibular gland, including the submandibular ganglionic cells, has been subjected to immunohistochemical examination with respect to expression of neuropeptides following fractionated irradiation with high energy photons. A markedly enhanced expression of bombesin- and leu-enkephalin-(ENK)-like immunoreactivities (LI) in the ganglionic cells and a pronounced increase in the number of nerve fibers showing these immunoreactivities in the submandibular gland tissue following irradiation were observed 10 days after treatment. On the other hand, no changes in the patterns of VIP (vasoactive intestinal polypeptide) and NPY (neuropeptide Y)-immunoreactivities occurred. Thus, the present study shows that alterations in the expression of certain neuropeptides take place in the submandibular gland and its associated ganglionic cells in response to irradiation of the head and neck region. These changes may add further explanation to the inherent radiosensitivity of salivary glands. PMID- 8472312 TI - Scintigraphic assessment of therapeutic aerosols. AB - Drugs are delivered to the upper or lower respiratory tract as aerosols via a range of inhalation devices in order to achieve either topical or systemic effects. It is important to be aware of the deposition pattern within the target organ inasmuch as treatment or prophylaxis will be effective only if sufficient drug is delivered directly to the required site. Drugs delivered to the nasal passages must be retained in the nose sufficiently long enough to exert a local effect or to be absorbed before they are removed by mucociliary clearance. Gamma scintigraphy is a noninvasive technique capable of giving information about total and regional deposition in the lungs, or deposition in and subsequent clearance from the nasal passages, thus providing data that are difficult or impossible to obtain by other means. Radiolabeling strategies for scintigraphic studies of the respiratory tract usually involve the radionuclide 99mTc, which is added to the formulation in order to trace the location of the drug substance in the body. It is difficult to find suitable gamma ray-emitting radionuclides for direct chemical labeling of drug molecules. Pharmacoscintigraphic studies, combining scintigraphy and conventional pharmacokinetics, are able to give valuable insights into the in vivo behavior of compounds delivered to the systemic circulation via the respiratory tract. PMID- 8472313 TI - Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency. AB - As we have reported previously, both DNA and tRNA become hypomethylated in livers of rats fed a cancer promoting, methyl-deficient diet (MDD) for as short a period as one week. Within the same period, activities of tRNA and DNA methyltransferases (MTases) increase and levels of mRNAs for several genes believed to have roles in growth regulation are altered. These diet-induced changes in nucleic acid methylation and gene expression increased in extent when MDD was fed continuously for four weeks. We also observed hypomethylation of specific CCGG sites within several genes for which mRNA levels were increased. These included c-myc, c-fos and c-Ha-ras. To investigate the reversibility of such diet-induced alterations in methylation and gene expression, animals were fed MDD for four weeks, after which a diet supplemented with adequate sources of methyl groups (CSD) was fed for 1-3 weeks. One to two weeks after the restoration of an adequate diet, the overall extent of methylation of tRNA and DNA from livers of these rats did not differ from that of tRNA and DNA from livers of age matched animals continually maintained on CSD. At the same time, activities of MTases in the liver dropped to normal values. Levels of mRNAs for all genes studied returned to control levels within three weeks after ending MDD feeding, although at different rates. In contrast, MDD-induced hypomethylation of some HpaII sites in c-myc, c-fos and c-Ha-ras genes persisted after 3 weeks refeeding of an adequate diet. These results, which demonstrate that most of the effects of MDD on the parameters we have studied occur rapidly and are essentially reversible, are consistent with the role of MDDs as promoters of hepatocarcinogenesis. However, the finding that unmethylated sites persist in genes that play a role in growth regulation suggests a mechanism by which intermittent or long term exposure to MDDs could result in heritable phenotypic changes in some hepatocytes that lead to hyperplasia and tumorigenesis. PMID- 8472314 TI - Increased poly(ADP-ribosyl)ation in intact cells by cisplatin treatment. AB - Cisplatin (DDP) is a clinically important antitumor drug that induces the formation of DNA-DNA and DNA-protein crosslinks. We have studied whether poly(ADP ribosyl)ation, a post-translational modification of nuclear proteins that is drastically increased by the presence of DNA strand breaks and plays a role in DNA repair, is induced following DDP treatment of cell cultures. By using an immunofluorescence technique for the in situ detection of poly(ADP-ribose) in intact cells, we found spotty nuclear signals after DDP treatment of O-342 rat ovarian tumor cells or CV-1 monkey cells, but not in untreated control cells, nor in DDP-treated cells postincubated with the ADP-ribosylation inhibitor 3 aminobenzamide. Our results thus provide direct evidence for an involvement of poly(ADP-ribosyl)ation in the cell's response to DDP treatment and, more generally, illustrate the versatility of this rapid in situ method for the detection of increased poly(ADP-ribosyl)ation in living cells. PMID- 8472315 TI - The glutathione S-transferases: polymerase chain reaction studies on the frequency of the GSTM1 0 genotype in patients with pituitary adenomas. AB - The frequency of the GSTM1 0 polymorphism at the glutathione S-transferase M1 locus has been determined in controls and patients with pituitary adenomas by using the polymerase chain reaction to amplify genomic DNA in the exon 4-5 region of the gene. The frequency of the genotype in patients with prolactinomas, non functional adenomas, corticotrophinomas and somatotrophinomas varied between 52 67% compared with 44% in the controls. In the patients with prolactinomas the frequency of the genotype (67%) was significantly greater than in controls with odds ratio analysis indicating that GSTM1 0 individuals have a 2.56-fold greater risk of developing this adenoma. PMID- 8472316 TI - Quantitation of tissue- and sex-specific induction of rat GSH transferase subunits by dietary 1,2-dithiole-3-thiones. AB - Male and female Sprague--Dawley rats were maintained for 5 days on control diet or diet containing 0.075% (w/w) 1,2-dithiole-3-thione (D3T) or 5-(2-pyrazinyl)-4 methyl-1,2-dithiole-3-thione (oltipraz). The content of GSH transferase (GST) subunits 1a, 1b, 2, 3, 4, 6, 7, 8, 10 and 11 in the soluble fraction of liver, kidney, small intestine, stomach and lung of control and D3T-fed animals was determined. Liver and kidney were similarly analysed for the oltipraz-fed animals. Significant induction of GST subunits by D3T was seen in all tissues, the most substantial being subunit 7 in male liver (approximately 50-fold) and subunits 1b, 3 and 10 in male and female small intestine (5- to 16-fold). Generally subunits 7, 10, 1b and 3 were most affected, while subunits 6 and 8 were hardly inducible. Oltipraz caused qualitatively similar inductions in the liver and kidney. The effect of GSH transferase induction on the hepatic capacity for GSH conjugation of aflatoxin B1 exo-8,9-oxide is assessed. PMID- 8472317 TI - A study on skin tumour formation in mice with 50 Hz magnetic field exposure. AB - In order to test the possibility that magnetic fields (MF) act as a tumour promoter, a long-term skin carcinogenicity study of 50 Hz sinusoidal MF with flux densities of 50 microT and 0.5 mT was performed in female NMRI mice. 7,12 dimethylbenz[a]anthracene (DMBA) in acetone was applied to the dorsal skin, as an initiator, and exposure to MF was performed for 19 (weekdays) or 21 h/day (weekends and holidays) for 103 weeks starting one week after the initiator treatment. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a positive control for skin tumour promoting activity. MF was also evaluated for complete carcinogenic action in groups of mice that were treated with acetone only. Six animals from each group were taken for skin hyperplasia analysis and were killed after 9, 26 and 52 weeks. The appearance of skin lesions were carefully followed and histopathological diagnosis was made for all neoplasms present at death. The statistical analyses on occurrence of skin tumour bearing animals and cumulated skin tumours, with corrections for survival did not reveal a difference between the controls and the MF exposed groups. The epithelial thickness of DMBA + MF-treated animals was of the same magnitude as for DMBA treated animals. Leukaemia was a little more frequent among animals exposed to 0.5 mT MF compared to the control animals. However this difference was not statistically significant. PMID- 8472318 TI - Differential growth control of normal, preneoplastic and neoplastic Syrian hamster embryo cells in serum-free media. AB - The objective of this work was to develop a serum-free medium that supported the growth of secondary Syrian hamster embryo (SHE) cells suitable for use in the morphological transformation assay (MTA). The current assay employs high levels of fetal bovine serum, each lot of which must be selected for its efficacy in the assay. To circumvent the problems associated with the use of serum, two serum free media (CGM-4 and CGM-9) were developed. The approach used was to replace serum with more defined hormones and growth factors. DME/F12 with low NaHCO3 (pH 6.7) was chosen as a basal nutrient medium since this pH has been reported to give enhanced transformation. Both serum-free media supported the clonal high density growth of normal secondary SHE cells. These media were also found to support the growth of several established SHE cell lines exhibiting successive stages of neoplastic progression. However, significant differential responses of the individual cell lines to CGM-4 and CGM-9 were observed, whereas, in serum supplemented medium all three lines responded similarly. These results raise the hope that CGM-4 and CGM-9 will be useful for studies of altered autocrine function during transformation and progression as well as for use in the transformation assay itself. PMID- 8472319 TI - Human hepatic CYP1A1 and CYP1A2 content, determined with specific anti-peptide antibodies, correlates with the mutagenic activation of PhIP. AB - Mono-specific antibodies targeted to human CYP1A1 and CYP1A2 have been produced by immunizing rabbits with protein conjugates of short synthetic peptides corresponding to residues 290-297 and 284-296 respectively, of these enzymes. The antibody targeted to CYP1A1 bound in immunoblotting to the recombinant protein expressed in yeast but did not bind to any human hepatic microsomal protein, whereas the antibody targeted to CYP1A2 bound only to this enzyme in immunoblotting of human hepatic microsomal fractions and did not recognize recombinant human CYP1A1. The intensity of hepatic microsomal CYP1A2 immunoreactivity (n = 5) correlated significantly with a number of activities characteristic of this enzyme: phenacetin O-deethylase (POD), ethoxyresorufin O deethylase (EROD) and methoxyresorufin O-demethylase activities and the ability to activate the dietary carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), to a mutagen. The anti-CYP1A2 anti-peptide antibody consistently inhibited both POD and EROD activities, but inhibition was incomplete (28%). In view of the known (> 90%) contribution of CYP1A2 to these activities and the correlation with antibody binding, this is consonant with an epitope for the anti CYP1A2 anti-peptide antibody that forms the edge of a functionally important proinhibitory surface region previously identified in rat cytochromes CYP1A. CYP1A2 immunoreactivity determined by immunoblotting correlated significantly with the ability of human hepatic microsomal fractions to activate 2-amino-1 methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), another dietary carcinogen, to a mutagen. It is concluded that CYP1A1 is absent from human liver and that CYP1A2 is likely to be a major catalyst in the hepatic activation of PhIP. PMID- 8472320 TI - The role of O6-alkylguanine-DNA alkyltransferase in protecting Rat4 cells against the mutagenic effects of O6-substituted guanine residues incorporated in codon 12 of the H-ras gene. AB - The role of rat O6-alkylguanine-DNA alkyltransferase (AGT) in modulating mutagenesis by O6-substituted guanines in the rat H-ras gene was examined. Rat4 cells were transfected with vectors carrying O6-methyl-, O6-ethyl- or O6 benzylguanine residues in place of the normal guanines at either the first, second, or both the first and second positions in codon 12 (GGA) of the H-ras coding sequence. The percentage of transformed colonies was determined for cells grown in normal medium or in medium containing O6-benzylguanine to completely deplete AGT. In parallel experiments with O6-methylguanine-containing vectors, the percentage of cellular DNA harboring codon 12 mutations was determined for normal cells and cells lacking AGT. A reasonable correspondence was observed between the percentage of mutated DNA and the percentage of transformed colonies produced in both types of cells. The results indicate that the contribution of AGT to the repair of O6-substituted guanine damage decreases as the O6 substituent is changed from methyl > ethyl > benzyl. Additionally, cellular AGT appears to repair an O6-methylguanine more readily at the first position of codon 12 than the second position. However, other repair mechanisms in these mammalian cells appear to play a major role in correcting low levels of O6-substituted guanine damage including O6-methylguanine damage. PMID- 8472321 TI - Sulfotransferase-mediated mutagenicity of 1-hydroxymethylpyrene and 4H cyclopenta[def]chrysen-4-ol and its enhancement by chloride anions. AB - 1-Hydroxymethylpyrene (HMP), a primary benzylic alcohol, and 4H cyclopenta[def]chrysen-4-ol (OH-CPC), a secondary benzylic alcohol, were investigated for mutagenicity in Salmonella typhimurium (reversion of the his- strain TA98) in the presence of various xenobiotic-metabolizing systems. In the direct test, HMP was inactive and OH-CPC was very weakly active. In the presence of NADPH-fortified postmitochondrial fraction from rat liver (S9/NADPH), no activation of OH-CPC was observed, whereas strong mutagenic effects were elicited by HMP. In the presence of cytosol and 3'-phosphoadenosine-5'-phosphosulfate (PAPS), both alcohols were activated to potent mutagens. For equal mutagenic effects, approximately 650-fold lower concentrations of HMP were required in the cytosol/PAPS-mediated assay than in the S9/NADPH-mediated assay. The cytosol/PAPS mediated mutagenicity of both alcohols was 3- to 4-fold enhanced, when KCl (125 mM) was present during the exposure. The authentic chloromethylarenes, 1 chloromethylpyrene and 4-chloro-4H-cyclopenta[def]chrysene, showed very strong direct mutagenicity. These results, taken together with previous findings, indicate that both primary and secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons may be activated by sulfotransferases to electrophilic sulfuric acid esters, and by subsequent substitution reaction to further active species such as benzylic chlorides. PMID- 8472322 TI - Expression of DNA methyltransferase in LEC rats during hepatocarcinogenesis. AB - The Long-Evans with a cinnamon-like color (LEC) rat is a mutant of the Long-Evans strain that develops hereditary hepatitis and hepatoma with ageing. Age-related changes in the mRNA expression of DNA methyltransferase (DNA MTase) were examined in livers of LEC rats using Long Evans with an agouti color (LEA) rats as controls. A dramatic increase in the expression of this mRNA was observed in LEC rats at 20 weeks when acute hepatitis appeared. Their high mRNA levels were maintained until 52 weeks of age. The mRNA expression as well as DNA MTase activities were found to be higher in cancer lesions than in adjacent normal tissue. These increases may be related to liver regeneration and to early events in cellular transformation of LEC rats. PMID- 8472323 TI - Temporal dissociation between cell proliferation and eosinophilic foci development in the exocrine pancreas of rats initiated with 4 hydroxyaminoquinoline 1-oxide and administered soybean trypsin inhibitor. AB - Male Sprague-Dawley rats received a single i.v. injection of 4 hydroxyaminoquinoline 1-oxide (HAQO) 7 mg/kg body weight or vehicle alone, and starting 7 days thereafter, were then fed basal diet with or without a 5% soybean trypsin inhibitor (SBTI) supplement. Subgroups were sequentially killed after 2, 4, 7, 14, 30, 60 and 100 days on this regimen, in each case 1 h after injection of bromodeoxyuridine (BrdU). In the HAQO/SBTI and SBTI alone groups, 2 days after the SBTI treatment the labeling indices of acinar cells were increased approximately 12- and 11-fold respectively, dropping rapidly thereafter and returning to the control value by day 30. The earliest eosinophilic foci were noted in the HAQO/SBTI group 60 days after HAQO initiation, with the component cells demonstrating markedly increased labeling indices in contrast to the completely normalized levels observed in the surrounding exocrine tissue. On the other hand, eosinophilic foci were scarcely induced in the HAQO or SBTI alone group throughout the experiment. These results thus indicate a clear temporal dissociation between initial proliferation in parenchymal pancreatic tissue caused by SBTI and subsequent development of eosinophilic foci in rats initiated with HAQO. PMID- 8472324 TI - Ability of peroxisome proliferators to induce cell transformation, chromosome aberrations and peroxisome proliferation in cultured Syrian hamster embryo cells. AB - Di(2-ethylhexyl)phthalate (DEHP), a commonly used plasticizer, induces proliferation of peroxisomes in liver cells and causes hepatocellular carcinomas when chronically administered in the diet to rodents. To examine possible mechanisms for DEHP-associated cancer, we have measured induction of morphological transformation, chromosome aberrations and peroxisome proliferations of cultured Syrian hamster embryo (SHE) cells by DEHP and other peroxisome proliferators. Morphological transformation of SHE cells was weakly induced by treatment for 48 h with DEHP and its metabolite mono(2 ethylhexyl)phthalate (MEHP). The transformation frequency by DEHP was enhanced by exogenous metabolic activation using rat liver postmitochondrial supernatants. Treatment for 24 h with DEHP resulted in chromosome aberrations of the cells only in the presence of exogenous metabolic activation. 2-(p-chlorophenoxy)-2 methylpropionic acid ethyl ester (clofibrate), a widely used hypolipidemic drug, failed to induce morphological transformation or chromosome aberrations of SHE cells. Treatment with [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (WY-14,643), which is a more potent carcinogen than DEHP or clofibrate, elicited a lower frequency of morphological transformation than DEHP in the presence of exogenous metabolic activation but was more active than DEHP at inducing chromosome aberrations. Similar levels of peroxisome proliferation, as determined by an intensity of diaminobenzidine staining, were observed in cultures treated for 2 h with DEHP, MEHP, clofibrate or WY-14,643. These results suggest a possible involvement of genetic damage by DEHP metabolites in the induction of cell transformation of SHE cells by DEHP; however, no clear relationship among induction of peroxisome proliferation, carcinogenicity in vivo and cell transformation was observed. Although the ability to induce cell transformation and chromosomal mutations is not adequate to explain the carcinogenicity of this class of compounds, these biological effects may be contributory to the carcinogenic activities of peroxisome proliferators. PMID- 8472325 TI - Species differences in the production and clearance of 1,3-butadiene metabolites: a mechanistic model indicates predominantly physiological, not biochemical, control. AB - Inhaled 1,3-butadiene, a monomer used in the production of synthetic rubber and other resins, is metabolized to mutagenic and carcinogenic epoxide intermediates. A physiologically based pharmacokinetic model of the uptake, tissue distribution, and metabolism of butadiene was constructed to determine if the biochemical kinetic constants obtained from in vitro studies are consistent with the observed in vivo uptake and metabolism. The model includes compartments for lung, blood, fat, liver, other rapidly perfused tissues ('viscera') and slowly perfused tissues. Metabolism of butadiene was assumed to occur in viscera in addition to lung and liver. Enzymatic reaction rate equations for the formation of 1,2-epoxy 3-butene, for hydrolysis of this epoxide, and for its conjugation with glutathione were also included. Physiological and biochemical parameters for the mouse, rat and human were obtained from the literature; they were not adjusted to produce a fit to experimental data. The model was used to test the hypothesis that differences in uptake and clearance of butadiene by the three species are due to differences in the activities of the metabolizing enzymes. The model reproduces whole-body observations for the mouse and rat. It predicts that inhalation uptake of butadiene and formation and retention of epoxybutene are controlled to a much greater extent by physiological parameters than by biochemical parameters and that storage in the fat represents a significant fraction of the retained butadiene. Accumulation of epoxybutene in the blood is predicted to be higher in mice than in rats or humans, but accumulation of the epoxide intermediate in the liver is predicted to be highest in humans. The epoxide tissue concentrations predicted by the model do not, by themselves, correlate with tumor incidence in mice and rats, indicating that other factors are crucial for carcinogenesis induced by butadiene. PMID- 8472326 TI - Carcinogenicity, metabolism and Ki-ras proto-oncogene activation by 7,12 dimethylbenz[a]anthracene in rainbow trout embryos. AB - Field studies suggest that recent epizootics of hepatic neoplasms in some feral fish populations are associated with polycyclic aromatic hydrocarbon (PAH) exposure, but attempts to induce liver tumors in these species under laboratory conditions have been unsuccessful. Several studies have shown hepatic neoplasma to be inducible in laboratory fish species following PAH exposure at the free swimming life stage. However, neither the susceptibility of the fish embryonic life stage to tumor induction by PAHs nor the potential of these carcinogens to induce oncogenic point mutations analogous to those reported in feral fish hepatic tumors have been clearly established. To address this, rainbow trout embryos were exposed by passive water uptake to 7,12-dimethylbenz[a]anthracene (DMBA), a potent model PAH in many mammalian tumor protocols. DMBA was rapidly absorbed by trout eggs and metabolized. The major non-polar metabolites identified were 12-hydroxymethyl-7-methylbenz[a]anthracene and 3,4-dihydroxy-3,4 dihydro-DMBA, whereas approximately 25% of the water soluble metabolites were identified as glucuronides by beta-glucuronidase treatment. Embryonic DNA adduction increased with time of DMBA exposure (2.2 +/- 0.3 pmol DMBA equivalents/mg DNA at 24 h). Liver tumor incidence nine months after DMBA treatment was found to increase with DMBA concentration and exposure period (3.8% at 1 p.p.m./2 h; 23% at 5 p.p.m./2 h; 85% at 5 p.p.m./24 h). Stomach adenomas and nephroblastomas also were observed at low incidence in the DMBA-treated trout. Among 11 hepatic tumors examined, nine carried Ki-ras alleles with activating point mutations in codon 12 (4/11 GGA-->AGA; 4/11 GGA-->GTA) or codon 61 (1/11 CAG-->CTG). This spectrum differs substantially from those reported for DMBA initiated mouse skin papillomas or hepatic tumors. These results may have important environmental implications because they suggest that even a brief exposure to PAHs during a sensitive stage of development may adversely affect some fish populations. They also indicate considerable variation in DMBA ras gene mutations among species and target organs. PMID- 8472327 TI - Genotoxic activity of 1-chloromethylpyrene in stomach epithelium in vivo: insensitivity of the stomach scintillation UDS assay. AB - An acknowledged weakness of current testing programmes for genotoxic hazard has been the potential insensitivity of the established mouse bone marrow micronucleus test and rat liver unscheduled DNA synthesis (UDS) assays to direct acting or short-lived mutagens, which may be consumed at the site of initial contact. In such cases, in vivo test systems sampling tissues such as the skin or the stomach would provide valuable data. To test these principles a stomach UDS assay was evaluated using the potent locally active mutagen 1-chloromethylpyrene (1-CMP). Contrary to expectations, no UDS response was observed 16 h following 1 CMP dosage by oral gavage. To confirm the integrity of the 1-CMP used for the stomach UDS assay, a sample of the stored chemical was re-evaluated in vitro and shown to be still strongly positive in the Ames assay and to have alkylating activity at least 15 min after incubation at stomach acid pH. No UDS response was observed when test dose levels were reduced or when earlier sampling times were used. Other genotoxic endpoints were examined in stomach. 32P-Postlabelling analysis revealed high levels of adduct formation in gastric DNA. An assay utilizing electrophoresis of DNA (the comet assay) showed the occurrence of DNA damage following dosing with 1-CMP in vivo. These positive results confirmed that 1-CMP should be regarded as a potential in vivo genotoxin. The failure to detect a UDS response to 1-CMP in stomach was investigated; a strong UDS response was observed in an in vitro hepatocyte UDS assay of 1-CMP indicating that the rat was capable of repairing 1-CMP-derived DNA adducts. Pretreatment of rats with hydroxyurea depressed the level of incorporation of thymidine into DNA both in negative and positive [methyl-N-nitrosoguanidine (MNNG)] controls. The results of these studies indicated that the protease digestion method employed did not selectively or efficiently sample those cells with any UDS response to 1-CMP or MNNG, and the activity seen for the latter was most likely due to the presence of S phase cells within the digests. As a result of the finding that UDS responses were not demonstrated for the potent direct-acting mutagens 1-CMP and MNNG, the protease digestion/scintillation method for stomach UDS does not appear to have general value in a screening programme for locally active genotoxic agents. PMID- 8472328 TI - Mutation in Escherichia coli and mammalian cells induced by closely spaced 1 methylpyrene-deoxyadenosine adducts in opposite DNA strands. AB - Twenty-eight base complementary oligonucleotides were synthesized with deoxyadenosine residues modified at the N6 position with 1-methylpyrene (MP) specifically positioned 3 bp apart in opposite DNA strands. Doubly modified constructs as well as non-modified and singly modified constructs were ligated into M13mp19 and an SV40-based shuttle vector pSVL-lac for transfection into Escherichia coli and large T-antigen-expressing monkey kidney epithelial cells respectively. Repair of MP adducts was analyzed by direct nucleotide sequencing after selection of clones containing the 28mer construct. In E. coli, double MP adducts induced base substitutions at positions mainly adjacent to modified adenines, while single MP adducts were not mutagenic. Single base insertions were also induced proximal to modified adenines. The frequency of mutation induced by double MP adducts in E. coli was approximately 4% (eight mutations out of 196 analyzed). In monkey kidney cells, double MP adducts induced one and three base deletions and single base insertions. Base substitution was observed in constructs containing non-modified and singly modified adenine residues, indicative of a significant spontaneous mutation rate. The frequency of mutation induced by double MP adducts in monkey kidney cells was approximately 9% (six mutations out of 66 clones analyzed). Modification of adenine residues by MP caused termination of DNA replication by E. coli DNA polymerase I (Klenow fragment) in vitro at the position opposite the MP adduct and at the preceding base. The repair of closely spaced polycyclic aromatic hydrocarbon adducts in opposite DNA strands is discussed as it relates to mutagenesis and carcinogenesis in mammalian cells. PMID- 8472329 TI - Promutagenic methylation damage in liver DNA of mice infected with Schistosoma mansoni. AB - Male and female BK-TO mice were infected with different numbers of Schistosoma mansoni cercariae under standard environmental conditions. Promutagenic methylation damage (O6-methyldeoxyguanosine; O6-MedG) was detected in liver DNA, but not in kidney, spleen or bladder DNA of infected animals. It was shown that levels of hepatic O6-MedG increased with increasing intensities of schistosomal infection. Possible mechanisms of action are discussed. These include the activating effects of schistosomes and their products on murine macrophages and subsequent endogenous formation of N-nitroso compounds by the activated macrophages. PMID- 8472330 TI - Vitamin E is a complete tumor promoter in mouse skin. AB - The dorsal skins of 6-8 week old female SENCAR mice were initiated with a single application of 10 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently promoted twice/week with topical applications of vitamin E (dl-alpha-tocopherol, 80 mumol/treatment). Vitamin E from two separate commercial suppliers was tested. For comparison, a group of similar mice, also initiated with DMBA, was promoted twice/week with the known tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA, 2 micrograms/treatment). Papillomas appeared 39 and 50 days respectively after promotion began with vitamin E from the two different sources, as compared with 32 days in the group receiving TPA promoted. Hundred per cent of TPA promoted animals and 92-96% of the vitamin E-promoted mice developed tumors. A maximum of 15 papillomas/animal appeared in the TPA-promoted mice. The two vitamin E preparations were somewhat less effective than TPA and showed different relative potencies, producing about seven and 12 papillomas per animal respectively. Unlike TPA, vitamin E showed very little ability to produce an inflammatory response in skin. To test whether initiated cells that did not appear as papillomas after vitamin E promotion were still viable, and had proceeded past stage I of promotion (conversion), the group that developed 12 papillomas/animal from vitamin E promotion was further promoted with mezerein, a stage II promoter. In this group, the papilloma frequency then increased to approximately 17/animal. The animals were followed over the course of their lifespan and monitored for skin carcinomas. In the TPA-promoted group 64% of the mice developed carcinomas, while the two vitamin E-promoted groups showed 48 and 60% incidence respectively. These results indicate that topically applied vitamin E acts as a complete tumor promoter in DMBA-initiated mouse skin, with an efficiency approaching that of TPA. Since vitamin E is a powerful antioxidant, they also suggest that reduction of cellular oxidant levels may trigger the tumor promotional process, and it may therefore be prudent to avoid repetitive or prolonged topical exposure of human skin to antioxidants like vitamin E. PMID- 8472331 TI - N-acetylation phenotype and genotype and risk of bladder cancer in benzidine exposed workers. AB - Several studies in subjects occupationally exposed to arylamine carcinogens have shown increased risks for bladder cancer associated with the slow acetylator phenotype. To follow up these reports, a case-control study of N-acetylation and bladder cancer risk was carried out among subjects occupationally exposed to benzidine, in benzidine dye production and use facilities in China. Thirty-eight bladder cancer cases and 43 controls from these factories were included for study of acetylation phenotype, by dapsone administration, and for polymorphisms in the NAT2 gene, by a polymerase chain reaction (PCR)-based test. In contrast to previous studies, no increase in bladder cancer risk was found for the slow N acetylation phenotype (OR = 0.3; 95% CI = 0.1-1.3) or for slow N-acetylation associated double mutations in NAT2 (OR = 0.5; 95% CI = 0.1-1.8). Examination of specific mutations and adjustment for age, weight, city and tobacco use did not alter the results. When examined by level of benzidine exposure in the cases, the bladder cancer risks associated with low (OR = 0.3, 95% CI = 0.0-2.2), medium (OR = 0.7, 95% CI = 0.1-4.5) and high (OR = 0.6, 95% CI = 0.1-3.5) exposure showed no interaction between genotype and benzidine exposure, within the range of exposures experienced by subjects in this study. This study, which is the first to incorporate phenotypic and genotypic analyses, provides evidence that the NAT2 related slow N-acetylation polymorphism is not associated with an increased risk of bladder cancer in workers exposed to benzidine, and may have a protective effect. PMID- 8472332 TI - Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues. AB - The effect of exposure to whole-body gamma-irradiation or fast electrons on O6 alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3 fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat. PMID- 8472333 TI - Species differences in the hydrolysis of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile. AB - The carcinogenic effects of acrylonitrile in rats are believed to be mediated by its DNA-reactive epoxide metabolite, 2-cyanoethylene oxide (CEO). Previous studies have shown that conjugation with glutathione is the major detoxication pathway for both acrylonitrile and CEO. This study investigated the role of epoxide hydrolase in the hydrolysis of CEO by HPLC analysis of the products from [2,3-14C]CEO. CEO is a relatively stable epoxide with a half-life of 99 min at 37 degrees C in sodium phosphate buffer (0.1 M), pH 7.3. Incubation with hepatic microsomes or cytosols from male F-344 rats or B6C3F1 mice did not enhance the rate of hydrolysis of CEO (0.69 nmol/min). Human hepatic microsomes significantly increased the rate of hydrolysis of CEO, whereas human hepatic cytosols did not. Human hepatic microsomal hydrolysis activity was heat-sensitive and potently inhibited by 1,1,1-trichloropropene oxide (IC50 of 23 microM), indicating that epoxide hydrolase was the catalyst. The hydrolysis of CEO catalyzed by hepatic microsomes from six individuals exhibited normal saturation kinetics with KM ranging from 0.6 to 3.2 mM and Vmax from 8.3 to 18.8 nmol hydrolysis products/min/mg protein. Pretreatment of rodents with phenobarbital or acetone induced hepatic microsomal hydrolysis activity toward CEO, whereas treatment with beta-naphthoflavone, dexamethasone or acrylonitrile itself was without effect. These data show that humans possess an additional detoxication pathway for CEO that is not active in rodents (but is inducible). The presence of an active epoxide hydrolase hydrolysis activity toward CEO in humans should be considered in assessments of cancer risk from acrylonitrile exposure. PMID- 8472334 TI - Intermediate biomarkers of colon cancer: modulation of expression of ras oncogene by chemopreventive agents during azoxymethane induced colon carcinogenesis. AB - In our attempts to evaluate the influence of chemopreventive agents on intermediate biomarkers of colon cancer, we have investigated the effect of D,L alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase and piroxicam, a non-steroidal anti-inflammatory drug (NSAID) on the expression levels of biochemically active p21ras, the protein product of cellular ras protooncogenes during the development of azoxymethane (AOM) induced colon carcinogenesis in male F344 rats in order to explore the plausibility of using p21ras as an intermediate biochemical marker of colon cancer. Groups of male F344 rats were fed the modified AIN-76A diets containing 0 or 150 p.p.m. piroxicam or 4000 p.p.m. DFMO and administered s.c. AOM dissolved in normal saline at a dose of 15 mg/kg body wt/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal vol of normal saline. Groups of animals were then killed at 0, 4, 16, 24 and 32 weeks after the last injection of AOM or saline and their colonic mucosa and tumors analyzed for biochemically active p21ras levels. AOM treatment significantly increased the expression of biochemically active p21ras. The AOM-induced expression of biochemically active p21ras was significantly suppressed by dietary DFMO and piroxicam. DFMO exerted a more pronounced inhibitory effect on AOM-induced colon tumor development as well as the expression of biochemically active p21ras. These results indicate that the determination of biochemically active p21ras may be effectively used in clinical chemoprevention trials as an intermediate end-point to monitor the colon carcinogenesis. PMID- 8472335 TI - Studies on the relationship between hemoglobin and DNA adducts of malonaldehyde and their stability in vivo. AB - The stability of the adducts of malonaldehyde (MA) to N-terminal valine in hemoglobin (Hb) and to guanine at N1,N2 in liver DNA was determined in vivo. Mice were injected with radiolabeled or unlabeled MA and the decay of the levels of Hb and DNA adducts was determined using the N-alkyl Edman method and the 32P postlabeling assay respectively. The rate of adduct formation was much higher towards valine in Hb than towards guanine in DNA. The highest level of adducts to valine was observed 4 h after the treatment, whereas the corresponding level for guanine was after approximately 120 h. The adduct to guanine in DNA was significantly more stable. The estimated half-lives of the adduct to N-terminal valine in Hb and for the adduct to guanine in DNA were approximately 6 and approximately 12.5 days respectively. The persistence of DNA adducts from MA in liver indicates that this type of adduct is poorly recognized by DNA repair enzymes and thus may accumulate during chronic exposure. PMID- 8472336 TI - Inhibition of 8-hydroxydeoxyguanosine formation by curcumin in mouse fibroblast cells. AB - Curcumin, a pigment responsible for the yellow color of curry, has been shown to be an anti-inflammation agent, an antioxidant and an antipromoter. 8 Hydroxydeoxyguanosine (8-OH-dG), an oxidized nucleoside, may be responsible for a genetic event of tumor promotion in carcinogenesis. 8-OH-dG can be detected selectively and sensitively at the fmol level by HPLC-electrochemical detection at an applied potential of +0.8 V versus Ag/AgCl. Phorbol-12-myristate-13-acetate (PMA), a potent tumor promoter, induces lipid peroxidation and 8-OH-dG formation. Curcumin can strongly scavenge the hydroxyl radical (OH.) to prevent 8-OH-dG formation from dG (deoxyguanosine) in vitro and reduce the production of PMA induced lipid peroxidation and 8-OH-dG in mouse fibroblast cells. These results suggest that curcumin inhibits the PMA-induced tumor promotion by functioning as an OH. radical scavenger to prevent 8-OH-dG formation within the DNA molecule. PMID- 8472337 TI - Differential effects of dietary beta-carotene on papilloma and carcinoma formation induced by an initiation-promotion protocol in SENCAR mouse skin. AB - SENCAR mice were used to determine the effects of the provitamin A compound beta carotene on papilloma formation and the conversion of papillomas to carcinomas in a two-stage protocol with one application of the initiator 7,12 dimethylbenz[a]anthracene (DMBA, 20 micrograms) and 20 weekly applications of the promotor 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 micrograms). A purified vitamin A-free diet was supplemented with beta-carotene at four levels (0.6, 6, 60 and 600 micrograms/g of diet) for female mice and two levels (60 and 600 micrograms/g) for male mice. Dietary supplementations of beta-carotene did not result in significant changes in body weight and survival of female and male mice. However, papillomas developed more rapidly and papilloma incidence (% mice with papillomas) reached its maximum (100%) sooner in male mice fed 600 micrograms of beta-carotene/g of diet than those fed 60 micrograms/g. There were smaller differences in papilloma incidence among the dietary groups in female mice, but the papilloma incidence again reached 100% sooner in mice fed 600 micrograms of beta-carotene/g of diet. Female and male mice fed 600 micrograms of beta-carotene/g of diet had significantly higher papilloma yields (average number of papillomas/mouse) than other dietary groups and a very low percentage of these papillomas converted to carcinomas in these mice. Thus, beta-carotene at 600 micrograms/g inhibited the conversion of papillomas to carcinomas in both sexes. In addition, papilloma yields were higher in female mice and these papillomas regressed more quickly than those in the corresponding groups of male mice. In conclusion, dietary beta-carotene caused differential effects on papilloma and carcinoma yields and sex-dependent differences in papilloma formation in female and male SENCAR mice treated with DMBA and TPA in a two-stage carcinogenesis protocol. PMID- 8472338 TI - Comparison of 12-O-tetradecanoylphorbol-13-acetate and teleocidin for induction of epidermal hyperplasia, activation of epidermal PKC isozymes and skin tumor promotion in SENCAR and C57BL/6 mice. AB - The present study compared the ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin to induce sustained epidermal hyperplasia, activate partially purified epidermal protein kinase C (PKC) isozymes and promote skin tumors in SENCAR and C57BL/6 mice. Teleocidin was less effective than TPA on a molar basis for inducing sustained epidermal hyperplasia, promoting skin tumors and activating partially purified epidermal PKC isozymes in vitro when examined using SENCAR mice. In contrast, teleocidin was more effective than TPA on a molar basis for inducing sustained epidermal hyperplasia, approximately equi-effective for promoting skin tumors and significantly less effective for activating PKC isozymes in vitro when examined using C57BL/6 mice. Despite the differences in response of C57BL/6 mice to TPA and teleocidin, this mouse strain was still highly resistant to skin tumor promotion by both types of promoters when compared with SENCAR mice. The current results, when considered in light of our recent studies (Cancer Res., 51, 1398-1405, 1991), indicate that C57BL/6 are generally resistant to a variety of classes of skin tumor promoters, including the teleocidins. In addition, except for the phorbol esters, the induction of sustained epidermal hyperplasia does not appear to be as good a marker for overall promotion responsiveness between SENCAR and C57BL/6 mice with other classes of tumor promoters; although the induction of a significant sustained hyperplasia in the latter mouse strain did yield a weak tumor response. Taken together, the current data suggest that factors in addition to the induction of sustained epidermal hyperplasia, control responsiveness of C57BL/6 mice to skin tumor promotion by diverse promoting stimuli. PMID- 8472339 TI - Specificity of mutations induced by N-methyl-N-nitrosourea in a cDNA of the hprt gene. AB - N-Methyl-N-nitrosourea (MNU) reacts with DNA to produce a variety of lesions, of which O6-methylguanine (O6-MeG) has been implicated in the mutagenic and carcinogenic effects of this agent. The present study aimed to investigate the types and position specificities of mutations induced by MNU. Mutational sequence alterations were determined for 53 independent mutations induced by MNU in a cDNA of the human hprt gene, which is stably integrated into chromosomes of the mouse cell line VH12. The majority of the mutations induced by MNU were base substitutions (85%), mostly GC to AT transitions (41/43), and the remainder (15%) were frameshift or deletion mutations resulting from loss or addition of a few bases. The transition mutations occurred preferentially at the middle G in 5' purine-G-N-3' sequences in the non-transcribed strand, and were distributed nonrandomly over the coding region of the gene. Analysis of the results suggests that, when interpreting mutational specificity and distribution, not only the nature of the mutational target sequence, but also the functional domains of the protein should be considered. PMID- 8472340 TI - Cell type-specific expression of the O6-alkylguanine-DNA alkyltransferase gene in normal human liver tissues as revealed by in situ hybridization. AB - The O6-alkylguanine-DNA alkyltransferase (ATase) is known to overcome the effects of promutagenic, precarcinogenic O6-alkylguanine induced in DNA by exposure to environmental, chemotherapeutic and dietary alkylating agents. Within an organ, the cell type-specific responses to these agents may be attributed, in part, to varying expression of critical DNA repair genes, like ATase. In order to determine the cell-specific expression of the human ATase gene, in situ hybridization was used to map the cellular distribution of ATase mRNA in tissue sections of normal human fetal and adult livers. Tissue sections were hybridized with a digoxigenin-labeled 39 base oligomer, antisense to ATase cDNA. Following immunodetection, using an alkaline phosphatase-conjugated anti-digoxigenin antibody, the ATase-specific mRNA levels were visualized in parallel with liver cell type identification. The specificity of the antisense probe and hybridization to human ATase mRNA was demonstrated by: (i) staining of Mer+ and not Mer- cells by the antisense probe; (ii) faint staining of liver sections when the antisense probe was not used during hybridization; (iii) no hybridization of liver sections by the sense probe; (iv) no staining of sections preincubated with RNase before hybridization; and (v) the retention of cell type-specific staining patterns in tissue sections incubated with DNase prior to hybridization with the antisense probe. The staining patterns appeared similar in adjacent sections of tissues obtained from the same liver and in sections obtained from either adult or fetal livers of different individuals. The expression of the ATase mRNA, as noted by stain intensity, appeared highest in all of the bile ductal cells. There was a heterogenous expression in hepatocytes, which varied from moderate to high stain. Staining in Kupffer cells also appeared to be high. Sinusoidal cells, endothelial cells of the hepatic artery and cells of the connective tissue showed weak hybridization, indicating low levels of ATase mRNA. These data explain, in part, the basis for a differential response of various cell types within the liver to the mutagenic and carcinogenic effects of alkylating agents. PMID- 8472341 TI - Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct. AB - To learn the reasons for the high incidence of biliary carcinoma in patients with anomalous arrangement of the pancreaticobiliary duct (APBD) mutagenicity of the bile of APBD-modeled dogs that had received a dorsal pancreatico-cholecystostomy was assayed by the Ames Salmonella mutation test. The bile from two out of 18 APBD dogs was mutagenic for Salmonella typhimurium strain TA98 under the condition of metabolic activation by rat liver S9 fraction, while the bile from 17 normal dogs was not mutagenic. Furthermore, the bile from five APBD dogs i.p. administered 1-nitropyrene (1-NP), which is a typical environmental mutagen, was more mutagenic for strain TA98 than that from 1-NP-treated normal dogs. The bile from the APBD dogs had very high amylase activity, indicating that the bile contained pancreatic juice as a result of the pancreatico-cholecystostomy. When pancreatic juice from a normal dog was added to the bile from 1-NP-treated normal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold. Furthermore, sulfatase increased the mutagenic activity of the bile in the presence of the pancreatic juice. HPLC revealed that the bile from a 1-NP-treated APBD dog contained mutagenic 1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, while bile from a 1-NP-treated normal dog did not contain these deconjugated products. The pancreatic juice from a normal dog had very high gamma-glutamyltransferase (GGT) and aminopeptidase activities and low sulfatase activity, but it had no beta glucuronidase activity. In addition, the bacteria that easily infect the biliary duct of APBD dogs, Escherichia coli, Klebsiella, Enterobacter and Proteus, had high beta-glucuronidase activity. In particular, Klebsiella showed a very high sulfatase activity. These results suggest that pancreatic juice enzymes and bacteria infecting the biliary duct deconjugate the detoxified mutagens in the bile and induce mutagenicity of the bile from APBD dogs or APBD patients. PMID- 8472342 TI - Inhibition by phenylethyl and phenylhexyl isothiocyanate of metabolism of and DNA methylation by N-nitrosomethylamylamine in rats. AB - We investigated the effect of 2-phenylethyl and 6-phenylhexyl isothiocyanate (PEITC and PHITC) on the metabolism of the rat esophageal carcinogen, N nitrosomethylamylamine (NMAA). PEITC was administered orally to MRC-Wistar rats as single doses of 0.1 or 1.0 mmol/kg, or by other regimens. When esophagi and liver slices from the treated rats were incubated with 23 microM NMAA, the formation of 2- to 5-hydroxy-NMAA was inhibited by 45-90% for esophagus and by 14 19% for liver slices. In contrast, when esophagi and liver slices from untreated MRC-Wistar rats were incubated in vitro with NMAA and 10 microM PEITC, the PEITC inhibited hydroxy-NMAA formation similarly (by 79-89%) in the two tissues. Also, PEITC inhibited the formation from NMAA of the hydroxy-NMAAs, formaldehyde and pentaldehyde by esophageal and liver microsomes to similar extents. In studies on DNA methylation by NMAA, 7- and O6-methylguanine (O6-MeG) were determined by HPLC with fluorimetric detection. Guanine methylation in esophageal and liver DNA was generally close to linear for doses of 5-50 mg NMAA/kg. With 50 mg NMAA/kg, guanine methylation in esophageal and liver DNA peaked after 5 h, and 8-11% of the peak O6-MeG persisted after 72 h. A single dose of 0.1 or 1.0 mmol PEITC/kg reduced the O6-MeG levels by 44-51% in the esophagus but by only 7-22% in the liver. Administration of the PEITC homolog, PHITC, inhibited NMAA metabolism by liver slices from the treated rats and the methylation of guanine in liver DNA, but had little effect in the esophagus, i.e. PHITC tended to have the opposite tissue specificity to PEITC. The finding that administration of PEITC specifically inhibited NMAA metabolism in the rat esophagus supports the view that PEITC may be a useful chemopreventive agent against esophageal carcinogenesis in humans. PMID- 8472343 TI - Increased expression of the female-predominant cytochrome P4502C12 in liver nodules from male Wistar rats. AB - Nodules and hepatomas from male and female rats treated according to the resistant hepatocyte (RH) model were analyzed with respect to expression of the male-predominant cytochrome P4502C11 (P450(16 alpha)) and the female-predominant cytochrome P4502C12 (P450(15 beta)) at the transcriptional and at the mRNA and protein levels. In male nodules isolated 8 and 11 to 12 months after initiation and in hepatomas, the expression of P450(16 alpha) mRNA was 3- to 11-fold lower than in surrounding liver, whereas a 2- to 8-fold higher expression of P450(15 beta) was observed compared with surrounding tissue. These alterations in P450 mRNA expression were reflected by similar changes at the protein level. Nuclear transcription of the cytochrome P450(16 alpha) gene was lower in male nodules than in surrounding liver whereas transcription of the P450(15 beta) gene was higher in the nodules. In nodules and hepatomas from female rats no significant differences in either mRNA expression or protein level of either P450(16 alpha) or P450(15 beta) were seen. The present study indicates that liver nodules are, to some extent, withdrawn from the normal endocrine regulation of rat liver function. Furthermore, the observed increase in a specific cytochrome P450 species (P450(15 beta)) in male liver nodules contradicts the previous suggestion of a general downregulation of this enzyme family as a characteristic of the nodular phenotype. PMID- 8472344 TI - The proximal promoter region of the human heme oxygenase gene contains elements involved in stimulation of transcriptional activity by a variety of agents including oxidants. AB - The rate of transcription of the heme oxygenase gene is enhanced by a variety of agents including oxidants such as hydrogen peroxide and UVA (320-380 nm) radiation and the sulfhydryl reagent, sodium arsenite. To further analyze the inducible response, we have isolated genomic clones of the human heme oxygenase gene. A 1.44 kb fragment corresponding to a region extending from 1416 bp upstream of the mRNA cap site to 24 bp into the 5' untranslated region of the mRNA has been further subcloned and sequenced and used as the basis for the construction of recombinant CAT transient expression vectors. By deleting large portions of this fragment, we have established that elements within 121 bp of sequence immediately upstream of the mRNA cap site respond to various agents (sodium arsenite, hydrogen peroxide, hemin, cadmium chloride and 12-O tetradecanoyl-phorbol-13-acetate) to give a 3- to 5-fold enhancement in transient expression of the reporter gene. Under the assay conditions employed, induction can only be detected when a SV40 enhancer element is present upstream of the promoter sequence. However, control experiments show that the SV40 sequences serve to amplify the response and are not directly involved in the induction itself. Only a small induction occurs when the entire 1.44 kb fragment is present. The results are consistent with the possibility that additional inducible enhancer elements lie outside of the sequence under study and that a silencer or negative regulatory element occurs upstream of the mRNA cap site within the 1.44 kb fragment. PMID- 8472345 TI - Reaction of cyclopenta[c,d]pyrene-3,4-epoxide with DNA and deoxynucleotides. AB - Cyclopenta[c,d]pyrene (CPP) is a widespread polycyclic aromatic hydrocarbon with potent mutagenic and carcinogenic activity. The trans isomer of 3,4-dihydro-3,4 dihydroxy-cyclopenta[c,d]pyrene has been shown to be the major metabolic product of CPP in rat, mouse or human microsomal systems, as well as in peroxyl radical generating systems, indicating the preferential formation of its obligatory precursor, CPP-3,4-epoxide. The direct mutagenicity of CPP-3,4-epoxide, the inactivity of 3,4-dihydro-CPP and the DNA adduct forming capacity of CPP in vivo has prompted analysis of the DNA adducts produced by CPP-3,4-epoxide to provide information pertaining to: (i) the role this postulated major ultimate mutagenic metabolite may play in the formation of DNA adducts in vivo; (ii) the base selectivity of CPP-3,4-epoxide DNA adducts; and (iii) the role of CPP-3,4-epoxide in the mutagenicity/carcinogenicity of CPP. CPP-3,4-epoxide was reacted with calf thymus DNA, dGp, dAp, dTp, dCp, poly dG-dC, poly dA-dT and poly dG. Adducts were analyzed by the butanol-enhanced version of 32P-postlabeling. Four major and at least three minor adducts formed with DNA in vitro, which were further analyzed for their base selectivity. A similar spectrum of adducts was exhibited by dGp, poly dG-dC and poly dG. dCp, dTp, and dAp formed one, two, and four adducts respectively. The relative binding in adducts per 10(7) nucleotides was in the following descending order: dGp (6000), poly dG-dC (5800), dTp (5300), dAp (4800), calf thymus DNA (3800), poly dA-dT (2300), poly dG (2600) and dCp (20). Adducts derived from either dGp, poly dG-dC or poly dG co-migrated with the DNA adducts in three solvent systems, indicating that CPP-3,4-epoxide forms DNA adducts almost exclusively with deoxyguanosine. PMID- 8472346 TI - Initiation and promotion of colonic aberrant crypt foci in rats by 5 hydroxymethyl-2-furaldehyde in thermolyzed sucrose. AB - We have previously shown that thermolyzed sucrose in the diet promotes the growth of aberrant crypt foci (ACF) in the rat. HPLC analysis of the light caramel colored product showed that it contained 1% 5-hydroxymethyl-2-furaldehyde (HMF), confirmed by mass and NMR spectroscopy. To determine whether HMF was responsible for the promotion of ACF by thermolyzed sucrose, 45 F344 female rats were initiated with the colon carcinogen azoxymethane (AOM), and a week later were randomized to four groups receiving AIN-76 diets containing untreated sucrose, 20% thermolyzed sucrose, 20% butanol extracted thermolyzed sucrose (HMF free) or 1% HMF. Thermolyzed sucrose in the diet led to larger ACF as previously observed. Thermolyzed sucrose extracted to remove HMF, did not affect ACF size, but 1% HMF added to the diet led to a larger ACF both with relation to average size and number of ACF of larger sizes (P < 0.05). To determine whether HMF had initiating effects, 172 female F344 rats were given water, HMF (at doses to 300 mg/kg) or AOM (5 mg/kg) by gavage twice and the total number of ACF was scored 30 days later. The results demonstrated that HMF induces ACF in a dose-dependent manner (P < 0.02), though the effect was much weaker than that of AOM. We conclude that sugar heated under household cooking conditions may act as both an initiator and a promoter of colon cancer because of the presence of HMF. PMID- 8472347 TI - Sucrose enhancement of the early steps of colon carcinogenesis in mice. AB - The association of refined sugars and colorectal cancers and polyps in three recent case-control studies led us to investigate the effects of sucrose, fructose and glucose on colonic epithelial proliferation and sensitivity to carcinogenesis. CF1 and C57BL/6J mice were used; proliferation was assessed as vincristine-accumulated mitotic figures per crypt section; sensitivity to carcinogenesis was assessed as the number of aberrant crypt foci (ACF) per colon observed following the colon carcinogen, azoxymethane (AOM, 3 mg/kg and 5 mg/kg). Oral gavages of sucrose and fructose in CF1 mice (10 g/kg) increased colonic proliferation 16 h later (2.8 +/- 0.6 and 4.1 +/- 0.7 (mean +/- SEM) accumulated mitotic figures/crypt section), compared with glucose and water (1.0 +/- 0.2 and 0.4 +/- 0.1). Sucrose and fructose given 14 h prior to the AOM (5 mg/kg) increased the sensitivity of the colon to carcinogenesis (18.4 +/- 1.5 and 13.1 +/- 1.8 ACF/colon), compared with glucose and water (11.4 +/- 2.0 and 8.6 +/- 1.1). Similar results were observed with C57BL/6J mice. We conclude that dietary sucrose and fructose may represent risk factors for colorectal cancer through a direct effect of the sugars on colonic epithelial proliferation. PMID- 8472348 TI - Prothrombin activation fragment assay. PMID- 8472349 TI - Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. AB - The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis. PMID- 8472350 TI - Enzyme immunoassay for intact human insulin in serum or plasma. AB - We describe an enzyme-linked two-site immunoassay for quantitation of intact insulin in human serum and plasma. The method uses two murine monoclonal antibodies that bind to two different epitopes on the insulin molecule. The immunoassay is specific. Human proinsulin is not bound by the antibodies, and the binding of partially processed proinsulin intermediates is believed to be of minor clinical importance. The relative response of human, bovine, and porcine insulin is 1, 1, and 3, respectively. The assay is sensitive (detection limit 5 pmol/L), accurate (101% recovery with 50 pmol/L insulin added to samples, 95% with 100 pmol/L, and 89% with 300 pmol/L), and fast (results within 3 h), and has a high analytical capacity (done in microtiter plates). The working assay range selected is 5-600 pmol/L, corresponding to a clinically useful range. Because of its specificity, this two-site immunoassay gives results that are lower than those obtained by using a competitive radioimmunoassay, both in normal individuals and in non-insulin-dependent diabetics. PMID- 8472351 TI - Carnitine measurements in liver, muscle tissue, and blood in normal subjects. AB - We determined carnitine concentrations in blood and in liver and abdominal muscle biopsy specimens in 13 men and 16 women undergoing elective surgery (mostly gallbladder removal). The data suggest that the carnitine pools of plasma and erythrocytes are different. The erythrocytes show a higher acylcarnitine concentration than does plasma (P < 0.001). Several reference bases for values in tissues have been used--dry weight, noncollagen protein (NCP), and DNA--because these may be differently influenced by disease. In liver specimens, the quotient NCP (g)/DNA (g) was significantly higher in men, 54.4 +/- 6.3 (mean +/- SD), than in women, 47.7 +/- 7.0 (P < 0.01). Liver total carnitine content in relation to DNA was significantly higher in men than in women: 0.29 +/- 0.06 vs 0.22 +/- 0.08 mmol/g DNA (P < 0.01). Free carnitine content was significantly higher in men than in women independently of the reference base, e.g., 3.7 +/- 1.0 mumol/g NCP for men vs 2.9 +/- 1.0 for women (P < 0.05). No difference was found between the sexes in the abdominal muscle carnitine content, 20.6 +/- 6.7 mumol/g NCP for men vs 17.9 +/- 5.0 for women. Our study establishes control ranges, thereby providing an important basis for studies of patients with abnormal carnitine metabolism. PMID- 8472352 TI - Urinary neopterin as a predictive marker of coronary artery abnormalities in Kawasaki syndrome. AB - We investigated whether urinary neopterin concentrations respond to the pathological conditions (especially coronary artery dilatation) of Kawasaki syndrome. All of 29 children with Kawasaki syndrome had very high urinary neopterin concentrations. Increased urinary neopterin concentrations coincided with fever and with monocytosis in peripheral blood. The urinary neopterin excretion peaking within the first 8 days after onset correlated with the development of coronary artery dilatation. Increased urinary neopterin concentrations indicate that cell-mediated immunity is activated in patients with Kawasaki syndrome. Endogenous interferon-gamma and activation of monocytes/macrophages may play a role in the pathogenesis of Kawasaki syndrome. Not only do neopterin concentrations correlate with symptoms in the acute phase of Kawasaki syndrome, they also act as a predictive marker of coronary artery abnormalities in affected patients. PMID- 8472353 TI - Characteristics and clinical application of a radiometric Escherichia coli-based phospholipase A2 assay modified for serum analysis. AB - Determination of activities of phospholipase A2 (PLA2) in human sera was based on the hydrolysis of phospholipids from [1-14C]oleic acid-labeled Escherichia coli biomembranes. The E. coli membranes served as substrate specifically for the PLA2 of human serum and were essentially resistant to other lipases in human sera, i.e., lipoprotein lipases, hepatic triacylglycerolipase, or pancreatic lipase in acute pancreatitis. Exchange of phospholipids between the serum and the biomembrane compartment aggravates the determination of PLA2 activity in human serum, which is naturally rich in phospholipids. In our modified E. coli assay, which overcomes these difficulties, the main substrate components phosphatidylethanolamine (70%) and cardiolipin (25%) were > 90% labeled in the sn 2 position. Fatty acids released by PLA2 activity were eluted from an aminopropyl solid-phase column directly into scintillation vials, where the radioactivity was counted. The ratio of [1-14C]oleic acid to released total fatty acids was used to calculate true enzymatic activity. The linear assay range extended from 0 to 3.6 U/L (0-60 nkat/L), with a detection limit of < 0.03 U/L (< 0.5 nkat/L). Within assay imprecision (CV) was < 6% and between-assay is < 10% over the whole activity range. The normal range for men was 0-0.44 U/L (0-7.33 nkat/L) and for women 0.044-1.11 U/L (0.73-18.4 nkat/L). Patients with septicemia, pancreatitis, acute respiratory distress syndrome, or other severe diseases had PLA2 values up to 540 U/L (9000 nkat/L). PMID- 8472354 TI - Increased urinary excretion of pyridinium cross-links in cancer patients. AB - Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects. Both cross-links were increased in cancer patients with and without clinically detectable bone metastases, although patients with bone and liver involvement had higher mean concentrations. The mean concentrations of both cross-links were also significantly higher in the urine samples of inpatients than in an outpatient ambulatory population. These findings suggest that the measurement of PYD and DPD in urine may be useful in assessing bone metastases and bone resorption in cancer patients. PMID- 8472355 TI - One-step competitive immunochromatographic assay for semiquantitative determination of lipoprotein(a) in plasma. AB - Numerous studies have associated high concentrations of lipoprotein(a) [Lp(a)] with atherosclerosis. We developed a rapid, one-step competitive immunochromatographic assay to measure Lp(a) in plasma. The assay is performed on a nitrocellulose membrane strip and the result is determined by a visual readout of rust-colored colloidal selenium. The assay is based on the principle that Lp(a) in the sample will compete with Lp(a)-coated colloidal selenium for binding to the anti-Lp(a) monoclonal antibody immobilized on the assay strip in the format of four ladder bars. The number of capture bars that appear as a result of the formation of colloidal selenium color is proportional to the concentration of the Lp(a) protein in the samples. The strip assay semiquantitatively measures Lp(a) concentrations ranging from 0 to 180 mg/L of Lp(a) protein in serum, plasma, or fingerstick whole-blood samples. This assay appears very useful for quick identification of individuals with above-normal concentrations of plasma Lp(a) protein (> 70 mg/L), and has potential for monitoring a patient's response to treatment with Lp(a)-lowering drugs. PMID- 8472356 TI - Specific glycation of albumin depends on its half-life. AB - Some suggest that measurements of plasma fructosamine concentration should be corrected for the plasma protein (or albumin) concentration because the extent of glycation per volume depends on both protein and glucose concentrations. Several reports, however, demonstrate a poor correlation between plasma fructosamine and albumin concentrations in diabetic patients. In vitro kinetic and in vivo studies have shown that glycation is also dependent on the half-lives of plasma proteins. Because a decrease in plasma albumin diminishes its catabolism, we speculated that low albumin concentrations are associated with a greater extent of glycation on a molar basis (specific glycation) and vice versa. To test this hypothesis, we studied plasma albumin, total protein, and fructosamine in 63 nondiabetic subjects with normal plasma fasting glucose concentrations and hemoglobin A1c between 5.1% and 5.9%. Plasma fructosamine was poorly correlated with albumin concentration (r = 0.348) but a logarithmic plot of the specific glycation of albumin vs albumin concentration showed a better correlation (r = -0.842), suggesting that the kinetic considerations were operating in vivo. Therefore, because lower specific glycation of plasma albumin "compensates" for higher concentration, correction of fructosamine for albumin content in patients will overestimate mean blood glucose when albumin is low and underestimate it when albumin is high. PMID- 8472357 TI - Measuring L-dopa in plasma and urine to monitor therapy of elderly patients with Parkinson disease treated with L-dopa and a dopa decarboxylase inhibitor. AB - We have established a method for measuring L-dopa in plasma and urine, including the metabolites dopamine and L-dopac, using separation by ion-pair reversed-phase HPLC and quantification with an electrochemical detector. The assay was applied to the therapeutic monitoring of elderly patients with established Parkinson disease being treated with L-dopa plus a dopa decarboxylase inhibitor. Plasma L dopa was evaluated in relation to dosage and postdose sampling time in 71 outpatients with Parkinson disease. L-Dopa concentrations were greatest in the patients taking the highest dosages prescribed and decreased significantly with increasing time after postdose sampling. Comparison of plasma L-dopa concentrations with a published therapeutic range established by intravenous administration of L-dopa was helpful in assessing the suitability of each patient's drug dosage, assessing patients' compliance, and avoiding overdosage but was not useful in the overall clinical assessment of progression of disease or of the long-term therapeutic response. Urine measurements confirmed the plasma concentrations but showed no further advantage. The recommended time for sample collection is between 1.5 and 3 h after the first morning dose. Plasma is the preferred matrix but if blood sampling is difficult, particularly from elderly/infirm individuals, an untimed urine collection could be used. PMID- 8472358 TI - Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. AB - We developed a radioimmunoassay (RIA) for the carboxy-terminal telopeptides of type I collagen (ICTP), cross-linked with the helical domain of another type I collagen molecule, after isolation from human femoral bone. The cross-linked peptide was liberated by digesting insoluble, denatured bone collagen either with bacterial collagenase or with trypsin, and purified by two successive reversed phase separations on HPLC, with monitoring of pyridinoline-specific fluorescence. The purity of the peptide was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its origin in the type I collagen fibers was determined by amino-terminal amino acid sequencing. Polyclonal antibodies and a separation reagent containing second antibody and polyethylene glycol are used in the RIA. An immunologically identical, somewhat larger antigen is present in human serum; its concentration increases in multiple myeloma and in rheumatoid arthritis. The ICTP antigen seems to be cleared from the circulation by the kidneys, because glomerular filtration rates that are two-thirds of normal or less are associated with increased circulating ICTP concentrations. The CVs of the method are between 3% and 8% for a wide range of concentrations. The analysis of 40 serum samples can be completed in 4 h. PMID- 8472359 TI - "Direct" and total bilirubin tests: contemporary problems. AB - In eight unique challenges mailed by The College of American Pathologists Comprehensive Chemistry Survey to participating laboratories within 3 years, results for direct-reacting bilirubin (DBIL) were highly variable among the 12 largest peer groups, and most of the results differed greatly from the values obtained by a referred method. Peer-group mean values for total bilirubin (TBIL) were in much better agreement with each other and with those obtained by the Reference Method for TBIL. From a review of the information on the assay of DBIL provided to us by the manufacturers, we conclude that among the major causes of the large variability and bias in DBIL assays are problems with calibration, lack of a serum blank measurement, inadequate concentrations of HCl in the reaction mixture, inappropriate use of bichromatic correction methods, and possibly the use of wetting agents or surfactants in the reagent. Within-group SDs were small and generally acceptable. The among-peer-group variability in DBIL values is attributable to bias, not imprecision. We recommend several simple changes that could improve the accuracy of DBIL determinations in clinical laboratories. PMID- 8472360 TI - Multicenter evaluation of Iso-ALP test kit for measurement of bone alkaline phosphatase activity in serum and plasma. AB - A test kit (Iso-ALP, Boehringer Mannheim) for measuring human bone alkaline phosphatase activity in serum or plasma was evaluated in five laboratories in three countries. The assay is based on the principle described by Rosalki and Foo (Clin Chem 1984;30:1182-6) and uses wheat germ lectin to precipitate bone alkaline phosphatase. Residual ALP in the supernate in comparison with total ALP is used to quantify the bone fraction. The imprecision of residual ALP measurement was low (median between-run CV 4.9%) and comparable with that of total ALP. Linearity of precipitation was demonstrable up to a bone ALP activity (diethanolamine buffer 37 degrees C) of 2000 U/L, though a matrix effect was observed for dilutions of high-activity sera in saline or bovine serum albumin. For assaying patients' samples, different batches of lectin demonstrated excellent comparability. Taking electrophoresis as a basis for standardization, we determined that the lectin precipitated approximately 90% of bone ALP, but < 5% of nonbone ALP. From this we derived serum/plasma upper reference limits for bone ALP activity in adults and children. PMID- 8472361 TI - Rapid determination of serum myoglobin with a routine chemistry analyzer. AB - A turbidimetric immunoassay system (Turbitime system, Behringwerke AG) allows rapid determination of myoglobin in serum. We adapted the reagents for this myoglobin assay (Turbiquant myoglobin) for use with a Hitachi 717 analyzer. No high-dose hook effect was observed up to 15,000 micrograms/L. Interassay CVs were 4.6% (mean = 72.0 micrograms/L; n = 9) and 2.5% (mean = 365.6 micrograms/L; n = 11). The calibration curve was stable for at least 1 month. Hemolysis did not interfere, and turbidity from lipemia interfered only when absorbance exceeded 2.0 A. Results of this method (y) correlated well with those by the Turbitime method (y = 1.256x - 44.1 micrograms/L; n = 91; r = 0.991) and by a commercially available radioimmunoassay (Byk-Sangtec; y = 0.739x - 42.2 micrograms/L; n = 94; r = 0.991). The upper limit (95th percentile) of the reference interval for myoglobin was estimated at 57.9 micrograms/L. The positive predictive value for results of myoglobin at admission was 89% with this upper reference limit and 99% with 100 micrograms/L, whereas the negative predictive value was about 60% for both limits. PMID- 8472362 TI - Comparison of lipid fatty acids on a concentration basis vs weight percentage basis in patients with and without coronary artery disease or diabetes. AB - Lipid fatty acid compositions are almost always expressed on a weight percentage basis rather than as weight or molar concentrations. With the former method of calculation, each fatty acid has an effect on the composition of the other fatty acids, an interdependence that can potentially lead to inaccurate and misleading results. Here we compare the concentrations per liter and the weight percentage compositions of cholesteryl ester and phospholipid fatty acids in individuals with and without coronary artery disease as well as free fatty acid compositions in individuals with and without diabetes. A new method for quantifying lipid fatty acids is also presented. Fatty acid results expressed as concentrations and those calculated on a weight percentage basis may lead to different conclusions, because significant differences between patient groups can be lost with the latter approach. We conclude that serum concentrations of lipid fatty acids are more accurate reflections of changes in lipid fatty acids than are weight percentage calculations, and are more easily interpreted in metabolic and therapeutic terms. PMID- 8472363 TI - Enzyme immunoassay--a new technique for estimating hemoglobin A1c. AB - We describe a method for estimating hemoglobin A1c (HbA1c) with a commercially available enzyme immunoassay system. The method is based on microtiter plate technology, utilizing an antibody raised to hemoglobin, the epitope being the Amadori product of glucose plus the first eight amino acids on the N-terminal end of the beta chain of hemoglobin. The enzyme immunoassay displays good within batch (CV 2.3-2.4%) and between-batch (CV 2.6-5.0%) precision, and the results were not affected by different types of anticoagulant. The method was linear within the expected range of results and showed good correlation (r = 0.88-0.98) with established methods for estimating glycohemoglobin. Using this method, we obtained a reference interval of 2.8-4.9% (central 95%) for HbA1c in a nondiabetic population. The percentages of hemoglobin that were HbA1c in diabetics (6.86% +/- 2.51%) were significantly greater (P < 0.001) than in nondiabetics (3.46% +/- 0.52%). PMID- 8472364 TI - Measurement of heroin and its metabolites by isotope-dilution electron-impact mass spectrometry. AB - A solid-phase extraction procedure was developed for the isolation of heroin, 6 acetylmorphine, and morphine from blood, plasma, saliva, and urine with subsequent assay by gas chromatography/mass spectrometry. Aprotic solvents, mild elution conditions, and an enzyme inhibitor were used to ensure maximum analyte stability. Samples were extracted and the extract was divided into two equal portions. One portion was assayed directly for heroin; detector response was linear over a concentration range of 1.0 to 250 micrograms/L. The second part of the extract was reacted with N-methyl-bis-trifluoroacetamide and assayed for the trifluoroacetyl derivatives of 6-acetylmorphine and morphine; detector response was linear over a concentration range of 1.0 to 500 micrograms/L. The limit of sensitivity was 1.0 microgram/L for each analyte. Hydrolysis of heroin to 6 acetylmorphine during extraction and analysis was < 5%. The method can be used to corroborate heroin use and to study the pharmacological effects of heroin and its metabolites. PMID- 8472365 TI - Clinical and laboratory studies of time-resolved fluorescence immunoassays of thyrotropin and free triiodothyronine. AB - We evaluated a new time-resolved immunofluorometric assay (TR-IFMA) for thyrotropin (TSH) and a time-resolved fluoroimmunoassay (TR-FIA) for free triiodothyronine (FT3) in serum. Delfia hTSH Ultra is a solid-phase two-site TR IFMA involving three monoclonal antibodies directed against different antigenic sites on the human TSH molecule. It offers improved analytical (+3 SD of zero) and functional (10% between-assay CV) detection limits of 0.001 and 0.016 mlU/L, respectively. Results of the assay agreed closely with those of a second generation immunoradiometric assay (TSH-IRMA) for samples with TSH > 0.2 mlU/L (n = 114). The nonparametric reference interval for TSH in euthyroid men and women was 0.5-4.7 mlU/L (n = 200). The TSH concentrations of hyperthyroid subjects (n = 29) were < 0.016 mlU/L (median; range < 0.016-0.063 mlU/L). The Delfia FT3 assay, a solid-phase TR-FIA, is based on the back-titration principle and second antibody separation. The parametric reference interval for FT3 in euthyroid men and women was 4.2-7.6 pmol/L (n = 320). The FT3 concentration in hyperthyroidism (n = 29) was 23 +/- 22 pmol/L (mean +/- SD; range 7.9-85 pmol/L). These methods offered rapid results (2-4 h for the whole procedure) and were simple to run. PMID- 8472366 TI - Effects of age, race, sex, and smoking on prothrombin fragment 1.2 in a healthy population. AB - Prothrombin fragment 1.2 (F1.2) is a biomarker of thrombin generation during blood coagulation and has diagnostic potential for assessing thrombotic risk and monitoring anticoagulation therapy. We used a monoclonal antibody-based immunoassay for plasma F1.2 to establish a well-defined reference interval and to evaluate the effects of age, race, sex, and smoking status on F1.2 concentrations in a healthy population. Plasma samples and demographic information were obtained from 357 healthy individuals. F1.2 concentrations more closely followed a lognormal than a gaussian frequency distribution. In a multiple linear-regression model in which the logarithms of F1.2 concentrations were regressed on age, race, sex, and smoking status, the significant explanatory variables were age and, to a lesser extent, sex and smoking. A segmented "hockey stick" regression model indicated that F1.2 concentrations and age were unrelated for individuals < 44 years old but were positively correlated above that age threshold. The estimated 95% tolerance interval (P = 0.95) for F1.2 in healthy individuals < 44 years old (n = 268) was 0.21-2.78 nmol/L. We conclude that age-matched F1.2 reference intervals may be important for studies evaluating the diagnostic utility of F1.2 measurements, and that the clinical relevance of increased thrombin generation during aging warrants further investigation. PMID- 8472367 TI - Automated spectrophotometric method for determining oxidized and reduced glutathione in liver. AB - An enzymatic recycling method has been applied to the measurement of total and oxidized glutathione with a centrifugal analyzer. When the reduced form of glutathione (GSH) was masked with 2-vinylpyridine to measure the oxidized glutathione (GSSG), the time to ensure full derivatization was three times longer than has been reported. The method is quick, simple, accurate, and precise (1.27% for GSH, 3.3% for GSSG intraassay CV; 2.15% for GSH, 5% for GSSG interassay CV), and the automation allows large numbers of samples to be conveniently assayed. PMID- 8472368 TI - Quantitative analysis of serum proteins separated by capillary electrophoresis. AB - The possibility of open tubular capillary electrophoresis for clinical diagnostic use is examined. Capillary electrophoresis was performed in an untreated 50 microns (i.d.) x 100 cm (65 cm to detector) capillary with detection of absorbance at 200 nm. Conditions for the separation of serum proteins without adsorption to the capillary surface were established. Quantitative analyses of serum samples from 38 patients with liver cirrhosis, nephrotic syndrome, or polyclonal gammopathy by capillary electrophoresis were done and the results were compared with those by conventional agarose gel electrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All samples were analyzed in duplicate. We evaluated linearity of response, within-run CV, and the correlation between capillary electrophoresis and agarose gel electrophoresis. PMID- 8472369 TI - A color test for methanol. PMID- 8472370 TI - Serum neopterin in acute rheumatic fever. PMID- 8472371 TI - Presence of endogenous digitalis-like factors in milk. PMID- 8472373 TI - Increased concentrations of fecal anti-gliadin IgA antibodies in untreated celiac disease. PMID- 8472372 TI - Cost-effective method for detection of "hook effect" in tumor marker immunometric assays. PMID- 8472374 TI - Strength of the signal, analytical variability, and predictive value of test results. PMID- 8472375 TI - Measurement of creatinine in urine screening for drugs of abuse. PMID- 8472376 TI - Trimethobenzamide cross-reacts in immunoassays of amphetamine/methamphetamine. PMID- 8472377 TI - Analysis of myeloma patients' specimens by the CEDIA Vitamin B12 & folate assays. PMID- 8472378 TI - Circulating proalbumin associated with a second case of antitrypsin Pittsburgh. AB - We report here the conclusive identification of circulating proalbumin of normal N-terminal sequence (Arg Gly Val Phe Arg Arg Asp Ala) in a second child with the alpha 1-antitrypsin Pittsburgh 358 Met-->Arg mutation. As in the first case, the proalbumin made up 3-5% of the total serum albumin. The finding of proalbumin associated with a second de novo mutation at the inhibitory site bait of antitrypsin confirms our earlier hypothesis; that antitrypsin Pittsburgh was acting as a specific intracellular inhibitor of the hepatic proalbumin convertase and that antitrypsin Pittsburgh could be used as a probe to identify the proprotein convertase. PMID- 8472379 TI - Gravimetric determination of the water concentration in whole blood, plasma and erythrocytes and correlations with hematological and clinicochemical parameters. AB - We have assessed gravimetric methods for determination of intravascular water, established whole blood-, plasma- and erythrocyte water reference values in a healthy volunteer group (n = 97, 48 females) and correlated these variables with 30 simultaneous hematological, clinicochemical and body parameters. The water standard was 55.56 mol/kg = 100 mass %. For erythrocyte water determination three methods were evaluated: 2 indirect methods were easy to perform, the third, using a hematocrit centrifuge, was the most reliable. Imprecision (within-batch coefficient of variation (CV), %) was excellent: whole blood 0.2, plasma 0.1, erythrocytes 0.7-2.2 and recoveries (means, %) 99.7-100.1. Serum water was found to be slightly higher than plasma water. Volunteer group, mean reference values, mass %: whole blood water 79.7, plasma water 91.2, erythrocyte water, three methods 66.2, 64.6 and 64.2, respectively. Females had mean 1.6 mass % higher whole blood water and 0.9-1.0 mass % higher erythrocyte water than males with no difference in plasma water. In the volunteer group whole blood water correlated strongly with hematocrit (r = -0.96), hemoglobin (r = -0.94) and erythrocytes (r = -0.85) and centrifuge hematocrit (r = -0.91). Plasma water correlated strongly with plasma total protein (r = -0.74, all correlations P < 0.001). Hemoglobin and hematocrit can serve as surrogate parameters for whole blood water when water determination is not available; total protein reflects plasma water. PMID- 8472380 TI - Circulating tumour-associated mucin concentrations, determined by the CASA assay, in healthy women. AB - This investigation was undertaken to establish a reference range for tumour associated MUC1 mucins in the serum of healthy women of the ages at risk for adenocarcinoma of the ovary and breast. Blood samples and clinical information were obtained from 5,000 women attending a breast screening mammography clinic. Data from women diagnosed with breast carcinoma and those subsequently diagnosed with other cancers were omitted from the reference range. Mucin concentrations were measured using the CASA assay which detects the protein core of MUC1 encoded mucins. Multiple linear regression analysis showed no effect on CASA concentrations by non-malignant changes to the breast, menopausal status, presence/absence of the reproductive tract, parity or history of hormone use. However, CASA concentrations were significantly increased in smokers (P < 0.001) and progressively increased with age (P < 0.001). These data show that these factors must be given consideration when setting upper limits of normal using MUC1 protein core binding assays. PMID- 8472381 TI - Determination of lipoprotein(a): enzyme immunoassay and immunoradiometric assay compared. AB - Lipoprotein(a) (Lp(a)) concentration in plasma is a strong independent risk factor for pre-mature atherosclerosis. Lp(a) closely resembles LDL. Its protein moiety contains apolipoprotein (apo) B-100 and apo(a). Two enzyme immunoassays (EIAs) for Lp(a) have been developed. In both, polyclonal antibodies for apo(a) are used as capturing antibodies. In the first, Lp(a) is detected with anti apo(a) (apo(a)-EIA). In the second, detection is carried out with anti-apo B (Lp(a):B-EIA). Neither plasminogen nor LDL cross-reacted in the assays. Lp(a) was also measured using a commercial sandwich immunoradiometric assay (IRMA). This assay uses two monoclonal antibodies for apo(a). One of them, the solid phase antibody, cross-reacted with plasminogen. However, at physiological plasminogen concentrations there was no competition for solid phase binding sites. A quantity of plasma samples (201) were assayed for Lp(a) with the three methods. The best correlation was obtained between the IRMA and the Lp(a):B-EIA (r = 0.909). Correlations between the apo(a)-EIA and the IRMA or the Lp(a):B-EIA were 0.763 and 0.695, respectively. As compared to the EIAs, the IRMA overestimated Lp(a) by about 30%. It is concluded that both the Lp(a):B-EIA and the IRMA reflect the concentration of Lp(a) particles in plasma. In contrast, the apo(a)-EIA measures apo(a) antigen and may therefore be susceptible to the size polymorphism of apo(a). PMID- 8472382 TI - Variability of kidney tubular interstitial distortions in glomerulonephritis as measured by 1H-NMR urinalysis. AB - 1H-NMR urinalysis is used for reliable non-invasive diagnostics of tubular and papillary distortions in glomerulonephritis. The study of urine from 52 patients with various clinical forms of the disease shows that these dysfunctions can manifest and develop independently of the degree of glomerular lesions at any stage of the glomerulonephritis. Tubular and papillary changes can be negligible even in terminal uremia and drastic in cases of clinically preserved kidney function. In addition, the results indicate that not only tubular interstitial changes, but also isolated tubular or papillary distortions can develop at any stage of the disease. Thus 1H-NMR urinalysis is suitable for diagnosing latent tubular interstitial changes which are not readily detected by traditional techniques. This is important since early tubular intervention worsens the prognosis of the glomerulonephritis progression. Thus an approach enables identification of a group at risk of rapid deterioration of the disease among patients whose serum has normal creatinine levels. This additional information is valuable for the proper treatment of patients, and makes 1H-NMR urinalysis a prospective method for screening urine in glomerulonephritis. Further studies are required to decide whether the technique can be recommended for clinical practice. PMID- 8472383 TI - Enzymatic determinations in acute rejection after liver transplantation: preliminary report on necrosis index. AB - The catalytic activities of some mitochondrial and cytoplasmic enzymes were measured in plasma from 19 patients after orthotopic liver transplantation, in order to detect and monitor the evolution of hepatocellular damage and to predict liver rejection. The enzymatic activities determined were: mitochondrial isoenzyme of aspartate aminotransferase, glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase and alkaline phosphatase. The results of all enzymatic activities were normalized by expressing them as multiples of the upper limit of the relevant reference range and then the necrosis index (NI) has been calculated. The proposed NI consists of percent ratio of the normalized mitochondrial enzymatic activities over the sum of cytoplasmic and mitochondrial normalized activities. We observed that NI values higher than 30% correctly identified all but two acute rejection events which were documented by liver biopsies showing a diagnostic sensitivity of 90%, specificity of 78% and a predictive value of 90%. PMID- 8472384 TI - Antioxidant defenses and its modulation by iron in carrageenan-induced inflammation in rats. AB - The concentration of endogenous antioxidants has been studied in rats with a carrageenan-induced granuloma. This animal model of inflammation allowed us to study the antioxidant defenses and the oxidative stress in plasma and in the site of inflammation (exudate) and their modulation by the levels of iron in the organism after iron-dextran or desferrioxamine administration. In inflamed rats without supplementary treatment, an interrelation between urate, ascorbate and vitamin E levels has been observed and it appears to be an important mechanism to prevent the depletion of the antioxidants. Further, the sulphydryl groups, caeruloplasmin and retinol also contribute to the defense in this experimental model. Iron overload increases the production of malondialdehyde and decreases some antioxidants such as ascorbic acid and SH groups but, on the other hand, it raises the levels of urate and caeruloplasmin. However, the protective effect of desferrioxamine has not been observed, and in our conditions this may be due to the induced mobilization of iron. Our results show that antioxidants have an important role in the prevention of lipid peroxidation by free radicals produced during inflammatory processes. This protective effect depends on the stage of inflammation. PMID- 8472385 TI - High performance liquid chromatographic determination of free and conjugated bile acids in serum, liver biopsies, bile, gastric juice and feces by fluorescence labeling. AB - Separation and measurement of commonly occurring free and conjugated bile acids in serum, liver biopsies, bile, gastric juice and feces have been successfully accomplished using high performance liquid chromatography with fluorescence labeling. Free and conjugated bile acids were extracted from pretreated samples using Sep-Pak C18 cartridges and then fractionated on a piperidinohydroxypropyl Sephadex LH-20 column. Free and glycine conjugated bile acids were labelled with 4-bromomethyl-7-methoxycoumarin. Taurine conjugated bile acids were hydrolysed with cholylglycine hydrolase prior to derivatization with 4-bromomethyl-7 methoxycoumarin. Labelled bile acids were eluted using an acetonitrile/methanol/water gradient on an ultrasphere ODS column. The eluate was monitored by a fluorophotometer at 360 nm (excitation) and 410 nm (emission). Linearity was obtained between 50 and 400 nmol. Recoveries from serum, gastric juice and feces were greater than 87%. This is therefore a sensitive method for the precise quantification of bile acids in serum, liver biopsies, bile, gastric juice and feces. PMID- 8472386 TI - Trace element concentrations (Cu, Zn, Fe) in sera from patients with dilated cardiomyopathy. AB - The trace element concentrations (Cu, Zn, Fe) in sera from patients with dilated cardiomyopathy are reported. Patients with dilated cardiomyopathy have high copper and low zinc concentrations in serum compared to healthy controls. The trace element concentration profile is different from that of other heart diseases like myocardial infarction and coronary heart disease. The copper concentration in serum shows a highly significant inverse relationship with the ejection fraction and the cardiac index. Pathophysiological processes which raise the copper concentration in serum may influence the ejection fraction and the cardiac index. PMID- 8472387 TI - Cholinesterases in cerebrospinal fluid in patients with meningitis and hydrocephaly. PMID- 8472388 TI - Plasma malondialdehyde in type 1 and type 2 diabetic patients. AB - Malondialdehyde, a marker of lipid peroxidation, was measured as thiobarbituric acid reactive substances (TBARS) in 117 diabetic patients and 53 controls. Patients were divided into groups and subgroups according to the type of diabetes (type 1 and type 2) and the existence or not of vascular complication (macro- or micro-angiopathy). Results showed that TBARS concentrations were significantly higher in type 1 (P < 0.0001) and type 2 (P < 0.001) diabetic patients than in the control group. The plasma TBARS concentrations in type 1 and type 2 diabetic patients did not differ significantly. Among the patients with vascular disease, type 2 diabetic patients with macroangiopathy had significantly higher TBARS concentrations than patients with no vascular complication (P < 0.05). Whichever the type of diabetes, there was no correlation between TBARS concentrations and glycaemic control: glycosylated haemoglobin, fasting blood glucose. This study confirmed the existence of lipid peroxidation disorders in diabetic patients. PMID- 8472390 TI - Contamination of biological samples in metal determination. PMID- 8472389 TI - Correction factors for single radial immunodiffusion and electroimmunodiffusion assays of IgA in secretory fluids. PMID- 8472391 TI - Biological variability of twenty-five serum analytes during normal pregnancy. PMID- 8472392 TI - Antioxidants and heart disease: epidemiology and clinical evidence. AB - One in three Americans will eventually die of cardiovascular disease. Antioxidant vitamins, which are postulated to reduce risk by about 20-30%, could have substantial clinical and public health impact. Basic research, clinical observation, and epidemiology have contributed to an emerging body of evidence on the atherogenicity of oxidized low-density lipoprotein, which could be an important mechanism to explain why antioxidant vitamins may decrease risk of coronary disease. The antioxidant-vitamin/cardiovascular-disease hypothesis has recently been explored in several large prospective cohort studies, but the findings were not all consistent. In several randomized, small-scale trials using subjects with existing vascular disease, data indicate benefits associated with vitamin E and beta carotene. Over the next several years, data from a number of ongoing primary prevention trials and proposed secondary prevention trials should determine whether antioxidant vitamins decrease risk of vascular disease. PMID- 8472393 TI - Vitamin E: more than an antioxidant. AB - The effect of vitamin E on platelet function has been reviewed. Although vitamin E inhibits platelet aggregation in vitro, in vivo it has no significant effect when administered in doses up to 1200 U/day. Platelet adhesion, on the contrary, is strongly inhibited by alpha-tocopherol. Doses of 400 IU/day provide greater than 75% inhibition of platelet adhesion to a variety of adhesive proteins when tested at low shear rate in a laminar flow chamber. The antiadhesive effect of vitamin E appears to be related to a reduction in the number and size of pseudopodia upon platelet activation. This effect of vitamin E may be related to changes in fatty acylation of structural platelet proteins. Clinical studies of vitamin E supplementation in patients with thromboembolic disease are in progress. PMID- 8472394 TI - Reactive oxygen metabolites, neutrophils, and the pathogenesis of ischemic tissue/reperfusion. AB - Considerable research effort has been directed at elucidating the mechanisms underlying the pathophysiologic alterations associated with reperfusion (reoxygenation) of ischemic (hypoxic) tissues. As a consequence of this intensive effort, a large body of evidence has accumulated, implicating a role for reactive oxygen metabolites and activated granulocytes in the genesis of postischemic cellular dysfunction. Figure 1 summarizes a hypothesis that has been proposed to explain the interaction of xanthine oxidase-derived oxidants, granulocyte infiltration, and the microvascular and parenchymal cell dysfunction that occurs in postischemic tissues. According to this scheme, xanthine oxidase-derived oxidants, produced at reperfusion, initiate the formation and release of proinflammatory agents, which subsequently attract and activate granulocytes. The activated neutrophils adhere to the microvascular endothelium, extravasate, and release cytotoxic oxidants and proteases, which contribute to tissue dysfunction. The aim of this review is to summarize the evidence that we and others have accumulated in support of this hypothesis. PMID- 8472395 TI - Oxidized LDL and atherogenesis: relation to risk factors for coronary heart disease. AB - According to a new theory, a critical step in atherogenesis is oxidation of low density lipoprotein (LDL) within the arterial wall. Direct data supporting this theory are limited, but indirect evidence suggests that oxidized LDL plays a role in atherogenesis. An important question is whether the LDL-oxidation hypothesis conforms to what is known about other risk factors for coronary heart disease (CHD), such as hypertension, smoking, low high-density lipoprotein (HDL) levels, and diabetes mellitus. Perhaps a unified theory of atherogenesis could be formulated if these risk factors exert their atherogenic actions in part by promoting, facilitating, or permitting the oxidation of LDL. PMID- 8472396 TI - Oxidized LDL and antioxidants. AB - Several studies have shown that the oxidative modification of low-density lipoprotein (LDL) may promote fatty-streak formation, the early lesion of atherosclerosis. Epidemiologic data suggest that decreased levels of micronutrient antioxidants are associated with an increased frequency of cardiovascular disease. Micronutrients that can act as antioxidants--ascorbic acid, alpha-tocopherol, and beta-carotene--have been shown to prevent LDL oxidation in vitro and retard the progression of atherosclerosis in animal models. In addition, supplementation of human subjects with these compounds have been shown to increase the resistance of their LDL to oxidation without producing side effects. Thus, these antioxidant micronutrients have the potential to become an additional treatment modality in the therapeutic arsenal against atherosclerosis. PMID- 8472397 TI - Expression of 67 kDa laminin receptor in human breast cancer cells: regulation by progestins. AB - The level of 67 kDa laminin receptor (67LR) expression on breast and colon tumor cell surfaces was previously shown to be correlated with the capacity of tumor cells to metastasize. In the present work we investigate the effects of progestins and estrogen on the expression of 67LR in two sublines of the T47D human breast cancer cells: weakly tumorigenic, poorly invasive parental T47D cells and a highly tumorigenic, more invasive T47Dco subclone. Immunoblotting with an affinity purified antibody directed against a synthetic peptide recognizes the 67LR in these cells. 67LR expression in the T47Dco subclone is 5.5 fold higher than in their parental T47D cells. Treatment of T47D cells with 1 nM of the synthetic progestin R5020 results in a 4-fold increase in 67LR protein expression. Estrogen also induced 67LR expression, but only by 1.5-fold. The progestin-stimulated expression of the 67LR correlates with a 4.3-fold increase in attachment of T47D cells to laminin. A monoclonal antibody, mAb 13, directed against beta 1 integrin, completely blocks the attachment of T47D cells to fibronectin, only partially inhibits the attachment of T47D cells to laminin, and appears not to affect the progestin-stimulated laminin attachment of T47D cells. A new antiprogestin, ZK 112.993, significantly inhibits both progestin-stimulated 67LR expression and the increased attachment to laminin. These results suggest a possible role for progestin in mediating one of the multiple events thought to be important in metastasis of steroid receptor positive human breast cancer cells. PMID- 8472399 TI - Soft-tissue sarcomas. Future perspectives. AB - Although the previous outlook for patients with soft-tissue tumors was poor, in recent years advances have been made in earlier recognition and management of soft-tissue sarcomas. Advances include improved clinical pathologic correlation and clinical staging, as well as improved concept of what constitutes adequate surgical management. In addition, recent advances in surgical adjuvant treatment programs promise better results. Moreover, a better understanding of the biology of cancer and the development of sophisticated techniques of molecular biology should lead to more effective treatment. PMID- 8472398 TI - Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide. AB - Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen. PMID- 8472400 TI - Osteogenesis imperfecta as a differential diagnosis of pathologic burst fractures of the spine. A case report. AB - A 22-year-old man suffered two noncontiguous burst fractures of the thoracic spine after minor motor vehicular trauma. He was diagnosed with pathologic spinal burst fracture associated with osteogenesis imperfecta Sillence Type 1A. The diagnosis was based on the relatively minor nature of the trauma, clinical characteristics, roentgenograms, and detailed family history. Osteogenesis imperfecta, although rare, should be considered in the differential diagnosis of severe burst fractures of the spine. PMID- 8472401 TI - Foraminal and extraforaminal lumbar disk herniations. AB - Thirteen patients with foraminal or extraforaminal lumbar disk herniation were treated during a 32-month period. Myelography and magnetic resonance imaging proved to be ineffective in identifying the lesion in most patients. High resolution computed tomography demonstrated the lesions in all patients, and the findings were subsequently confirmed at surgery. Surgical treatment consisting of disk fragment removal and nerve root decompression was effective in relieving radicular pain. PMID- 8472402 TI - Lumbar spinal stenosis secondary to calcium pyrophosphate crystal deposition (pseudogout). AB - A 62-year-old man demonstrated symptoms, signs, and radiographic evidence of lumbar spinal stenosis and intraoperative pathologic findings of tophaceous deposition in the ligamentum flavum. Although there have been reports of cervical calcium pyrophosphate dihydrate crystal deposition (CPPD) with neurologic compression, this report appears to be the first case of lumbar spinal stenosis secondary to CPPD. Cervical calcium pyrophosphate dihydrate crystal deposition should be added to the differential diagnosis of spinal stenosis. PMID- 8472403 TI - Biomechanical comparison of bone graft used in anterior spinal reconstruction. Freeze-dried demineralized femoral segments versus fresh fibular segments and tricortical iliac blocks in autopsy specimens. AB - This study compares the compression strength of frozen corticocancellous iliac blocks and short fibular segments with freeze-dried, partially ("surface") demineralized microperforated (FDPDM) short femoral segments. Three blocks from each iliac crest and segments from the fibular and femoral diaphyses were retrieved. The femoral segments were microperforated, demineralized for 24 hours, and freeze-dried. All were then loaded to failure in a stress testing machine. The FDPDM showed a significantly higher failure load and stiffness than the fibular segments and the iliac crest segments. The femoral and fibular segments were similar in strength but significantly higher than iliac crest grafts. Compared with commonly used frozen grafts, freeze-dried partially demineralized femoral segments may be used safely as axial load-bearing struts in anterior spine reconstruction. PMID- 8472404 TI - Osteonecrosis of the humeral head in sickle cell disease. AB - The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults. PMID- 8472405 TI - Supporting layers of the glenohumeral joint. An anatomic study. AB - Based on anatomic and surgical dissections, the anatomy of the shoulder region is described in terms of four layers that overlie and support the glenohumeral joint. Each layer envelops the glenohumeral joint on its anterior, lateral, and posterior aspects, and between each layer there is a plane for safe and easy dissection. Layer 1 is composed of the deltoid and pectoralis major muscle bellies with their overlying fascia and enveloping epimysium. Anteriorly, Layer 2 consists of the clavipectoral fascia, the conjoined tendon of the short head of the biceps and coracobrachialis, and the coracoacromial ligament. Posteriorly, Layer 2 is the dense posterior scapular fascia that overlies the infraspinatus and teres minor muscle bellies. It is continuous with the clavipectoral fascia around the lateral aspect of the proximal humerus. Deep to Layer 2, the subdeltoid bursa yields a dissection plane that encompasses the anterior, lateral, superior, and variably the posterior aspects of the glenohumeral joint. Layer 3 consists of the deep layer of the subdeltoid bursa and the underlying musculotendinous units of the rotator cuff, including subscapularis, supraspinatus, infraspinatus, and teres minor. Layer 4 is the capsule of the glenohumeral joint. This includes the glenohumeral ligaments and coracohumeral ligament. These four layers were present and consistent in each shoulder dissected. Significant variations were present only within the deepest layer (shoulder joint capsule). This system can serve as a learning tool and will provide a more organized approach to facilitate surgical dissection in the region. PMID- 8472406 TI - Acute prosthetic replacement for severe fractures of the proximal humerus. AB - Nineteen patients with 20 severe proximal humeral fractures were treated early with a Neer humeral prosthesis from 1979 to 1986. There were 18 four-part and two three-part fractures. The average age of the patients at the time of injury was 64 years. Follow-up evaluation was performed at an average of 40 months. Pain relief was satisfactory in 18 of 20 fractures. Patients were satisfied with the result in 16 of the 20 shoulders. Functional evaluation was good or fair in 15 of 20 patients. Active forward elevation averaged 72 degrees and active external rotation 16 degrees. Complications consisted of one axillary nerve palsy, one postoperative posterior dislocation, loosening of one uncemented humeral prosthesis, and one breakage of fixation wire requiring subsequent removal. Patients who could not comply with the postoperative rehabilitation program had poor results. Poor function appeared to be directly related to lack of rotator cuff integrity. Surgical techniques designed to securing tuberosity union are essential. PMID- 8472407 TI - Cemented versus cementless total hip arthroplasty. A comparative study of equivalent patient populations. AB - Seventy-one cemented total hip arthroplasties (THAs) in 66 patients were compared with 70 cementless THAs in 61 patients. The cemented and cementless components were identical except for the presence of a porous proximal surface on the cementless component. The mean follow-up time was 4.3 years in the cemented group and 4.1 years in the cementless group, with a minimum follow-up of two years. Postoperative Charnley pain scores were identical for both groups, as was the incidence of limp. The final Charnley function score, however was significantly higher in the cementless group (5.6) than in the cemented group (5.1). One revision was performed in the cemented group, none in the cementless group. Complete demarcation of the bone-cement interface was presented in two cemented components and was associated with subsidence. Three cementless components had early subsidence, and two of these had complete radiopaque lines around the porous surface. None of these three patients, however, had unsatisfactory pain or function scores. The most important finding of this study is the equivalence of clinical results noted in both cemented and cementless THA as late as six years after operation. PMID- 8472408 TI - Occurrence and incidence of the second hip fracture. AB - During a 16-year period, 256 second hip fractures were found in 3898 persons 40 years of age and older who had a previous hip fracture. Ninety-two percent of the second fractures were contralateral, and 68% of these were the same type as the first. Thus, 62% of the femoral neck and 72% of the trochanteric fractures were preceded by a contralateral fracture of the same type. The mean interval between fractures was 3.3 years, and there was no significant difference between genders or among fracture types. The risk of the first fracture was 1.6 per 1000 men per year and 3.6 per 1000 women, and for the second fracture 15 per 1000 men per year and 22 per 1000 women. This increase was highly significant for both genders, especially for men. PMID- 8472409 TI - Long-term evaluation of hip arthroplasty in patients with an ipsilateral knee arthrodesis. AB - Hip arthroplasty with an ipsilateral knee arthrodesis occurs infrequently but does raise concern regarding surgical technical difficulties, dislocation, sepsis, and long-term loosening. Sixteen patients were evaluated 7.5 years (average period) after surgery. Technical difficulties were not prohibitive. No dislocation or revision was necessary in any of the cases. Two patients died as a result of unrelated sepsis from an infected knee. Loosening and protrusio of the acetabulum occurred in two patients. Hip arthroplasty in patients with a fused knee does not incur undue risk of loosening or instability and can provide long term good function and pain relief. Patients with multiple joint arthroplasties, in whom concurrent sepsis occurs, can have devastating results. PMID- 8472410 TI - A comparison of the perioperative morbidity in total joint arthroplasty in the obese and nonobese patient. AB - The goal of this study was to determine if obesity is a risk factor for total joint arthroplasty. This was a retrospective review of 130 patients treated with either primary total hip arthroplasty or primary total knee arthroplasty during a two-year period (154 consecutive arthroplasties). The patients were placed in the nonobese or obese group. Obesity was defined as 20% above ideal weight for height, based on life insurance tables. There were 51 in the nonobese groups and 103 in the obese group. Charts were reviewed for a number of factors associated with postoperative complications. Operative time, intravenous fluids administered, and total blood loss were found to be slightly higher in the obese group. Only the difference in operative time proved statistically significant, however. The hospitalization time, number of days with a fever, number of transfusions, preoperative and postoperative hemoglobin levels, and days requiring intramuscular narcotics were very similar between the two groups. There were 0.29 minor complications per nonobese patient, but only 0.22 per obese patient. Major complications were encountered 0.22 times per nonobese patient and 0.10 times per obese patient. The patient is not necessarily at a higher risk for peroperative complications in total joint arthroplasty. The longevity of the implant in the obese patient was not determined in this perioperative study. PMID- 8472411 TI - Three-dimensional modeling of cartilage thickness in hip dysplasia. AB - The cartilage thickness in both normal hips and in coxarthrosis secondary to hip dysplasia was examined using a computer model. The hip cartilage thickness was calculated in three dimensions from computed tomographic images of the hip joint. In normal hip joints, the anterior cartilage was thicker than the posterior cartilage. In hip joints affected by secondary coxarthrosis, the cartilage thinned as the disease progressed. Approximately 80% of patients demonstrated thinning of the anterior apical cartilage, resulting in a forward and upward displacement of the femoral head. PMID- 8472412 TI - Rapidly progressive protrusio acetabuli in patients with rheumatoid arthritis. AB - Current literature suggests protrusio acetabuli in patients with rheumatoid arthritis progresses at a gradual rate of 2-3 mm per year. This report presents five patients with rheumatoid arthritis (RA) who experienced rapidly progressive protrusio. The period of rapid clinical progression averaged 40 days. During progression, medial protrusio increased an average of 7.5 mm, superior protrusio advanced 6.9 mm, femoral head width decreased 2.7 mm and center-edge angle increased 20.7 degrees. Axial protrusio occurred along an axis 137 degrees from vertical. A key clinical feature was an absence of significant hip symptoms before a marked increase in symptoms over a period of days to several weeks, resulting in a significant decrease in the patient's ambulatory capacity. Osteopenia was a consistent preexisting radiographic feature. The findings underscore the existence of rapidly progressive protrusio in the natural history of RA and its importance in the differential diagnosis of hip pain in patients with RA. Early recognition is important to minimize the potential complications of delayed surgical treatment. PMID- 8472413 TI - Principles of staging of soft-tissue sarcomas. AB - The TNM staging system is a modus for diagnosis and treatment in which T is the extent of the tumor involvement, N is lymph node involvement, and M is the metastases; this system is supplemented with a histologic malignancy grade. Staging systems identify specific prognostic factors with which to predict clinical outcome. Staging systems are useful for assigning treatment priorities, determining the role of adjuvant therapies, and evaluating clinical investigations. Unfortunately, no universally accepted staging system for soft tissue sarcomas exists. This is related to the relatively low incidence of sarcomas, the unique and unpredictable behavior of sarcomas, significant disagreement regarding histogenesis and grading, and lack of consensus regarding the value of various prognostic factors. In adults, the two most commonly used staging systems are those developed by the American Joint Committee on Cancer and by Enneking. In children, the Intergroup Rhabdomyosarcoma Study and the International Union Against Cancer have described the systems most commonly used. These systems for soft-tissue sarcomas rely on an ability to accurately determine both the local and distant extent of disease. Advances in the field of computed tomography and magnetic resonance imaging have made this possible. It is likely that a staging system based upon a more sophisticated understanding of the basic biology of sarcomas will become available. PMID- 8472414 TI - Roentgenographic assessment of the hip-knee-ankle axis in medial gonarthrosis. A study of reproducibility. AB - A preoperative reliable recording of the knee alignment is necessary to calculate the correct wedge at high tibial osteotomy for medial gonarthrosis. To determine the reproducibility of the hip-knee-ankle angle (HKA), a preoperative, whole lower limb roentgenogram was obtained twice in eight patients, and each roentgenogram was judged by two radiologists. Assessment of the HKA had a variability of at most 2 degrees, which is highly significant for a reliable calculation of the wedge at tibial osteotomy. PMID- 8472415 TI - Indications and results of nonoperative treatment of patellar fractures. AB - It is uncontested that most patellar fractures have to be treated by open reduction and internal fixation. Nevertheless, there are well-defined types of patellar fractures in which such a procedure is unnecessary because the fracture is stable and the retropatellar surface is congruous. In these fractures internal fixation would constitute overtreatment; conservative treatment yields good results in such cases. In this report, 40 patellar fractures treated conservatively were reviewed (average, 30.5 months after injury). Results were assessed subjectively and objectively. Of the 40 patients, 80% were pain free and 90% had a full range of knee motion. PMID- 8472416 TI - Surgical treatment of unresolved Osgood-Schlatter lesion. AB - The Osgood-Schlatter lesion is considered a traction apophysitis. Treatment is generally conservative, and only rarely does a surgical treatment become necessary for the persistence of pain and swelling over the tibial tubercle. The most widely used procedure consists of the excision of all intratendinous ossicles with or without removal of the prominent tibial tubercle. In 15 cases treated in this manner compared with 11 cases treated with various procedures before 1975, the results were clearly better with the former. There was only one fair and no poor results. Removal of all loose intratendinous ossicles associated with prominent tibial tubercles is the procedure of choice, both from the functional and the cosmetic point of view. PMID- 8472417 TI - Primary repair of quadriceps tendon ruptures. Results of treatment. AB - Results of primary repair of 19 quadriceps tendon ruptures in 19 patients were studied. Average patient age was 47.4 years. Predisposition to the site of tear according to age was noted. Seventy-five percent (nine of 12) of patients older than 40 years of age had ruptures at the tendon-bone junction, and 71% (five of seven) of patients younger than 40 years had ruptures at the midtendinous area. Repair for injuries in the midtendon-musculotendinous junction consisted of debridement, freshening of the edges, and reapproximation. Ruptures in the tendon bone junction required suturing through three to four holes drilled through the proximal pole of the patella. Postoperatively, patients were immobilized for six weeks. Excellent results were noted in all 17 patients who had early repair and good results in two patients who had delayed repair. Patient age, gender, mechanism of injury, site of rupture, and type of repair did not affect the outcome of treatment. PMID- 8472418 TI - Morphologic changes in the human patellar tendon after bone-tendon-bone anterior cruciate ligament reconstruction. AB - Magnetic resonance imaging (MRI) was performed on 15 patients, an average of 2.5 years after arthroscopically assisted bone-tendon-bone (BTB) anterior cruciate ligament (ACL) reconstruction, to evaluate the patellar tendon donor site. Five patients who had arthroscopically assisted ACL reconstruction using the semitendinosus tendon as a graft also were scanned bilaterally and evaluated. The mean difference between the involved and uninvolved patellar tendon length was 0.2 mm for the BTB patients and -2.6 mm for the semitendinosus patients. The mean difference between patellar tendon width for the BTB patients was 1.1 mm and 1.9 mm for the semitendinosus patients. The mean difference between patellar tendon thickness was 0.4 mm for the BTB surgery group and 0.02 mm for the semitendinosus surgery group. None of the differences were statistically significant. Results indicate that harvesting the central one third of the patellar tendon does not significantly affect the length, width, or thickness of the tendon at least 22 months after arthroscopically assisted BTB-ACL. PMID- 8472419 TI - A new method using computed tomographic scan to measure the rectus femoris patellar tendon Q-angle comparison with conventional method. AB - The Q-angle should be the angle generated by a line connecting the anteroinferior iliac spine (AIIS), the bottom of the groove of the femoral condyle, and the tibial tubercle. The Q-angle was measured by computed tomography (CT) in 43 lower limbs with recurrent patellar dislocation and 26 normal controls. The mean Q angle was 20 degrees in the dislocated group and 13 degrees in controls, a significant difference. No significant difference was found in the Q-angle between the dislocated and control groups using the conventional method. Lower limb rotation had little effect on accuracy of the method. PMID- 8472420 TI - Adhesions of distal tibiofibular syndesmosis. A cause of chronic ankle pain after fracture. AB - Ankle pain after uncomplicated ankle fractures poses a diagnostic and therapeutic challenge, especially in joints that exhibit insignificant radiographic changes. Ankle joint arthroscopy has become an important diagnostic and therapeutic tool for such cases. Adhesion of the distal tibiofibular syndesmosis, as yet an undescribed entity, was found to be the cause of chronic ankle pain in 11 of 19 patients suffering from chronic ankle pain after an uncomplicated fracture of the ankle. Symptoms resolved after arthroscopic resection of the adhesions in all 11 patients. Arthroscopy has an important role in diagnosis and management of unexplained ankle pain after a seemingly uncomplicated fracture. PMID- 8472421 TI - Transfibular compression arthrodesis of the ankle joint. AB - Eleven ankle arthrodeses were performed on ten patients using a transfibular technique. This technique employs a lateral approach in which the distal fibula is resected while preserving the peroneal tendon sheath, allowing excellent exposure and contouring of the tibiotalar joint. Compression is attained by using a T-plate placed across the tibiotalar joint with the aid of an AO compression apparatus. At 2.5 years after operation, fusion was achieved in ten ankles. Average time in immobilization was 11.8 weeks, and the fused ankle was cosmetically pleasing. Fusion occurred in nine of 11 ankles fused using other methods during this period. Pin tract infection occurred in three, the time in immobilization averaged 16.2 weeks, and the cosmetic result was inferior. PMID- 8472422 TI - Elective foot surgery in limbs with arterial disease. AB - Surgical correction of foot deformities is generally indicated to relieve the disability. The presence or suspicion of arterial disease may lead to the reluctance to operate because of the concern that healing might not occur, however. Twenty-three patients were referred for vascular assessment before elective foot surgery. There was little or no evidence of arterial disease in 15 limbs. In eight limbs there was unequivocal evidence of complete obstruction in the main limb artery. Contrary to what might be expected, healing after surgery occurred without difficulties in the limbs with arterial obstruction. The arterial disease as assessed by laboratory methods was not severe. The results indicate that elective foot surgery can be safely undertaken in some limbs. Simple laboratory methods for assessment of arterial circulation include measurements of distal blood pressure, skin temperature, transcutaneous oxygen tension, and assessment of digital pulsatility. A useful approach for estimating the chances of healing after elective surgery in limbs with arterial obstruction is formulated on the basis of the clinical and laboratory assessment. PMID- 8472423 TI - Osteosarcoma of the patella. A case report. AB - A 34-year-old woman complained of pain and swelling in the left patella. Because of roentgenogram showed hardly any destruction of the patella, she was not initially treated for a bone tumor. The clinical course followed the initial symptoms of a respiratory disorder with pulmonary metastatic foci. A bone tumor was first suspected after aspiration cytology of a lung tumor mass. A left patellectomy was performed to relieve the pain and confirm the diagnosis. The pain was relieved by the operation, but respiratory failure set in and progressed rapidly. The patient died three days later. Histologic examination showed that the tumor tissue consisted of atypical cells, spindle to polygonal in shape. The marrow space of the patella was predominantly occupied by neoplastic cartilaginous tissue. The pathologic diagnosis was primary chondroblastic osteosarcoma of the patella. PMID- 8472424 TI - Wound complication in surgery of soft tissue sarcoma. Analysis of 103 consecutive patients managed without adjuvant therapy. AB - In a consecutive series of 103 patients with soft tissue sarcoma, operated on from 1987 through 1990, clinical and perioperative factors were assessed for the development of wound complications. Local excision was performed in 98 cases and amputation in five. None had preoperative radiation therapy or chemotherapy. The overall incidence of wound complication was 40%. There were 16 infections, 13 necroses, and 12 hematomas. The complication rate was significantly lower in the upper extremity (17%) as compared with the trunk and lower extremity (45%). Superficially located and deep tumors had equal incidences of wound complications. Regarding deep tumors, wound complication was significantly related to large tumor size, old age, long operating time, and excessive blood loss. No such correlations could be found for superficial tumors. The median hospitalization time for patients with deep tumors who developed complications was 23 days, as compared with 11 days for those without. Complications in patients with superficial tumors did not lead to a lengthened hospital stay. A considerable complication rate was associated with limb-sparing surgery for soft tissue sarcomas. This incidence could probably be reduced by taking into account risk factors associated with wound complications, better preoperative planning, and close cooperation with plastic surgeons for adequate wound coverage. PMID- 8472425 TI - The effects of therapeutic doses of irradiation on experimental bone graft incorporation over a porous-coated segmental defect endoprosthesis. AB - The incorporation of autogeneic bone graft into a porous coated segmental endoprosthesis after high-dose irradiation was studied in dogs. A mid-diaphyseal defect was surgically created and then reconstructed with a porous-coated segmental endoprosthesis in 16 dogs. Autogeneic bone grafts were placed over the porous-coated regions of the endoprosthesis and at the endoprosthesis-bone junctions to achieve extracortical fixation. In eight dogs, the reconstructed femora were treated with a time-equivalent dose of 5500 cGy, delivered over a five-week period, beginning three weeks after surgery. In eight dogs, which served as the control group, the reconstructed femora were not irradiated. Dogs were killed 12 weeks after surgery, and the reconstructed femora were evaluated clinically, roentgenographically, mechanically, and histologically. Extracortical bone formation and bone ingrowth into the porous-coated segmental endoprosthesis were significantly inhibited by high-dose irradiation. Nonirradiated reconstructed femora had higher maximum torque at the implant-bone junction than irradiated femora. Nonirradiated femora had significantly greater bone ingrowth within the porous space than irradiated femora. Intracortically, irradiated femora had greater unlabeled bone and less porosity as well as more new bone than nonirradiated femora at 12 weeks postsurgery. Extracortically, irradiated femora had greater original cortical bone and less porosity as well as more new bone than nonirradiated femora at 12 weeks postsurgery. Mineral apposition was less in the irradiated femora from the initiation of radiotherapy to the time of killing five weeks after cessation of irradiation. PMID- 8472426 TI - The effect of anterior cruciate ligament resection and immediate or delayed implantation of a meniscus prosthesis on knee joint biomechanics and cartilage. An experimental study in rabbits. AB - In a rabbit experiment with anterior cruciate ligament (ACL) resection, immediate substitution of the medial meniscus with a prosthesis was compared with delayed prosthetic implantation after a postmeniscectomy period of three weeks. The knees with a prosthetic implant were compared with their contralateral joints as well as to joints with an intact ACL and menisci. Anterior cruciate ligament resection alone led to disturbed biomechanics and cartilage degeneration. Anterior cruciate ligament resection in combination with meniscus resection increased cartilage degeneration and led to more inferior biomechanics. Ingrowth and stable fixation was less frequent when the prosthesis was inserted three weeks after meniscus resection than when inserted immediately. Furthermore, in knees with delayed prosthetic implantation, only minor improvement in terms of cartilage protection was shown when compared with knees with resection only. In contrast, knees with immediate meniscus replacement demonstrated similar joint stiffness and stress relaxation characteristics and similar cartilage protection effects as knees with a nonresected medial meniscus. PMID- 8472427 TI - The effects of an artificial meniscus substitute in a knee joint with a resected anterior cruciate ligament. An experimental study in rabbits. AB - A Dacron meniscus prosthesis was substituted for the medial meniscus in an anterior cruciate ligament (ACL) resected rabbit knee. At three months, the joints were evaluated biomechanically, with gross and histologic inspection. In a paired comparison with the contralateral knee, differences between ACL resection with intact, incised, or resected medial menisci were evaluated. Knees with intact menisci and ligaments served as controls. Because of cartilage destruction, soft-tissue hypertrophy, and increased anterior laxity, joint stiffness was less than normal in all ACL-resected knees. Ingrowth and stable fixation, especially of the posterior horns of the prostheses and the incised menisci, were rare. Almost all normal menisci had ruptured in the same area. Anterior cruciate ligament resection led to severe osteoarthrosis in both compartments, regardless of initial meniscal treatment. Knees with prostheses had the same incidence and severity of osteoarthrosis as knees with meniscus resection. Anterior cruciate ligament resection alone induced excessive osteoarthrosis and synovitis and diminished the effects of different meniscal treatments three months earlier. PMID- 8472428 TI - Pharmacologic and clinical aspects of intraarticular injection of hyaluronate. AB - Hyaluronate (HA) is linear unbranched polysaccharide consisting of repeating disaccharide units of (1-4)-D-glucuronic acid-beta-(1-3)-D-N-acetylglucosamine. Extensive research has been conducted on HA, a major component of connective tissue. Hyaluronate, molecular weight 80 x 10(4)d, is available for the intraarticular injective treatment of osteoarthrosis of the knee and periarthritis of the shoulder. Hyaluronate relieves pain and has metabolic effects on articular cartilage, synovial tissue, and synovial fluid. Hyaluronate is a safe and effective treatment for patients with osteoarthrosis of the knee and periarthritis of the shoulder. PMID- 8472429 TI - Gene expression during bone repair. AB - Detailed understanding of the basic events in fracture healing constitutes a foundation for the development of new approaches to stimulate bone healing. Since the fracture healing process repeats, in an adult organism, several stages of skeletal growth in the same temporal order, it offers an interesting model for developmental regulation of cellular phenotypes and tissue-specific genes. Molecular biology has introduced new methods to study the regulatory phenomena during the process of fracture repair. Gene technology has also produced purified growth factors for research, which will help to understand their roles in fracture healing. This review summarizes data on the regulation of genes coding for extracellular matrix components and growth regulatory molecules during fracture healing. The information available focuses on the sequential expression of genes coding for collagens, proteoglycans, and some other matrix proteins during secondary (callus) healing. The temporal and spatial appearance of the different connective tissue components, mesenchyme, cartilage, and bone, are closely linked to the expression of genes coding for their characteristic constituents. Members of the transforming growth factor-beta superfamily, such as the bone morphogenetic proteins (BMP), are currently the most interesting ones among the factors that regulate chondrogenesis and osteogenesis. In the coming years, the availability of new cloned probes combined with sensitive analytical methods, as reviewed here, will add greatly to our understanding of the various aspects of gene expression during bone repair. This information should provide answers to some of the unresolved questions in fracture callus development. PMID- 8472430 TI - Biopsy of soft-tissue tumors. AB - Biopsy is an integral part of the overall management of patients with soft-tissue sarcoma. The types of biopsy are fine needle, trocar, open incision or en bloc excision. There are advantages and disadvantages of each. Open biopsy requires strict adherence to a number of surgical principles. Proper execution requires determination of appropriate biopsy site, meticulous technique, and close collaboration with an experienced pathologist. Failure to adhere to these principles may result in untoward consequences for patients. PMID- 8472431 TI - Rhabdomyosarcoma. AB - In children and young adults, rhabdomyosarcoma occurs with a frequency that is equal to or greater than that of all the other forms of soft-tissue sarcoma combined. Although the responsiveness of rhabdomyosarcoma to chemotherapy varies greatly among tumors with different primary sites and with different histologic features, the overall results of chemotherapy have been more impressive in rhabdomyosarcoma than in any other form of soft-tissue sarcoma. Rhabdomyosarcomas occur in almost all sites and age groups. Those that occur in trunk and extremity sites have an unusually high instance of alveolar or undifferentiated histologic features and are more common in older children and young adults. Although they constitute only one third of all patients with rhabdomyosarcoma, tumors that are primary in trunk and extremity sites present some of the most difficult therapeutic problems in the management of all patients with this tumor. The ability to accomplish an initial complete local tumor excision still represents a major factor in survival. Early reexcision in the case of incompletely excised tumors with small volumes of residual tumor is effective when feasible. Local control of rhabdomyosarcoma can be achieved by high-dose irradiation and frequently by lower-dose irradiation when given in conjunction with chemotherapy. Second-look surgery is an accurate predictor of outcome, and late excision of residual tumor after chemotherapy-radiation therapy regimens may influence outcome. A regimen of vincristine, actinomycin-D, and cyclophosphamide given as a "pulse", with or without Adriamycin (doxorubicin), is the standard chemotherapy with cisplatin, etoposide, melphalan, and other agents now under study in trials of the Intergroup Rhabdomyosarcoma Study. PMID- 8472432 TI - Liposarcoma. AB - Liposarcoma is second in frequency only to malignant fibrous histiocytoma among the soft-tissue sarcomas. It occurs almost exclusively in adults and is found most often in the thigh or retroperitoneum. It rarely arises from a lipoma and does not occur in the subcutaneous tissues. Liposarcomas are divided into histologic subtypes with different microscopic appearances and slightly different behavior characteristics. Surgical resection with a wide surgical margin is the treatment of choice. When amputation is required to obtain an adequate surgical margin, local irradiation can be used as an adjuvant and a limb-sparing operation can be done. Currently, no evidence exists that adjuvant chemotherapy is indicated for patients with liposarcoma, although numerous studies are being done to investigate its use. As is the case for all sarcomas, the lung is the most common site of metastasis; however, liposarcoma has an unusual propensity to metastasize to the retroperitoneum, mediastinum, and bone. PMID- 8472433 TI - Management of extremity soft-tissue sarcomas. AB - Management of extremity soft-tissue sarcomas requires accurate clinical staging, pathologic diagnosis, surgical resection with a wide margin, and adjuvant radiation therapy for high-grade lesions. Brachytherapy offers a clean benefit in local control for large (> 5 cm) high-grade sarcomas. The role of radiation therapy for small high-grade and all low-grade soft-tissue sarcomas still is being evaluated. Survival is function of histologic grade, age of patient, size and location of the tumor, metastases, and adequacy of the surgical resection. Efficacy of chemotherapy has yet to be proven. PMID- 8472434 TI - Integration of limb-sparing surgery, brachytherapy, and external-beam irradiation in the treatment of soft-tissue sarcomas. AB - Advances in the integration of limb-sparing surgery and adjuvant radiation therapy have nearly eliminated the need for ablative or radical resections in the management of soft-tissue sarcomas. The combination of wide or marginal surgical resections, brachytherapy, and external-beam irradiation resulted in a local recurrence rate of 9% in 68 patients followed for a minimum of two years. All recurrences were in nonsubcutaneous high-grade lesions. Treatment-related morbidity occurred in 22% of patients. Wound-healing complications developed in 17% and resolved with nonoperative treatment in half. These results support the efficacy of limb-sparing surgery and adjuvant radiation therapy in the management of soft-tissue sarcomas. Integration of chemotherapy may be necessary for the higher-grade lesions, although effectiveness is uncertain. PMID- 8472435 TI - Adjuvant chemotherapy in the treatment of soft-tissue sarcoma. AB - Standard therapy for treatment of soft-tissue sarcoma dictates adequate surgical resection with or without radiation therapy. However, metastases occur in a substantial proportion of cases, and, if improvement in survival is to be obtained, elimination of hematogenously borne micrometastasis will be required. A number of randomized, controlled clinical trials have been performed evaluating the use of cytotoxic chemotherapy in the treatment of localized soft-tissue sarcoma. Single-arm studies evaluating the use of intraarterial chemotherapy as an adjunct to limb-sparing surgery have been reported. Many of these studies have methodologic weaknesses, and have yielded conflicting results. Reviewed in detail, these studies are evaluated in the light of opportunities for clinical research. PMID- 8472436 TI - Chemotherapy for soft-tissue sarcomas. AB - Single-agent and combination chemotherapy have greater than 20% single-agent activity: doxorubicin and ifosfamide. Certain other anthracycline analogues possess similar activity. It remains a question whether combination therapy is any better than single-agent doxorubicin. Randomized trials have demonstrated enhanced response rates and increased toxicity for the combinations, but survival, with limited follow-up data, is not improved. The role of adjuvant chemotherapy also is not yet established. Two of 12 trials demonstrate survival benefits; however, most show a delay in relapse with about a 10% risk of irreversible toxicity. New agents, targets, and methods to circumvent resistance mechanisms developed in the laboratory are necessary to advance the field. PMID- 8472437 TI - Combined percutaneous and "minimal" internal fixation for displaced articular fractures of the calcaneus. AB - Forty-one displaced intraarticular fractures of the calcaneus in 38 patients were treated with open reduction and screw fixation of the posterior facet, bone grafting, and percutaneous pinning of the body. A single extensile posterolateral approach was used in all but two cases in which an additional medial incision was needed. Using early functional aftercare, all fractures healed without secondary displacement in an average of eight weeks. Follow-up periods averaged 4.2 years. Results were graded as excellent in 14 patients, good in 16, fair in three, and poor in five. There was a strict correlation between the clinical results and the severity of the articular comminution. A satisfactory outcome depended on the restoration of articular congruency and extraarticular alignment of the os calcis. PMID- 8472438 TI - Surgical management of calcaneal fractures using bilateral incisions and minimal internal fixation. AB - Nine patients with displaced calcaneal fractures were approached through bilateral incisions and stabilized with minimal internal fixation. All patients were men, with an average age of 35 years (range, 19-65). All fracture patterns had three-part split depression fractures of the posterior facet, a single intact sustentacular tali fragment, middle facet, and anterior body fractures. The reduction of tubercle impaction and varus angulation was accomplished by stabilization of the sustentacular tali-posterior tubercle fracture line through a modified medial vertical incision. Minimal fixation using either a three-prong staple or 4-mm lag screws was sufficient to stabilize this fracture pattern. Posterolateral facet articular elevation, and final reconstruction of Bohler's and Gissane's angles were performed through an extended lateral incision. Five of nine calcanei were stabilized with lag screws only and four required minimal lateral plate osteosynthesis. Preoperative Bohler's and Gissane's angles averaged 6 degrees and 138 degrees; postoperative angles averaged 34 degrees and 123 degrees, respectively. The average difference between postoperative Bohler's and Gissane's angles compared with the normal contralateral side was 1 degree each. There was no loss of reduction, and healing was uneventful. There was anatomic reconstruction of both medial and lateral cortexes in all cases. In this specific fracture pattern, medial stabilization of the sustentacular talitubercle fracture line can reduce both the amount and extent of lateral fixation, facilitate anatomic reduction of the posterior facet, and reduce postoperative implant sequelae after internal fixation. PMID- 8472439 TI - Open reduction and circular external fixation of intraarticular calcaneal fractures. AB - Open reduction and internal fixation techniques do not allow early weight bearing. In an effort to develop a better method to obtain calcaneal fracture reduction and maintain it in the face of early weight bearing, a circular external fixator was applied to seven patients in combination with a limited lateral approach and open reduction and internal fixation of the depressed subtalar joint fragments. The operative technique uses the Ilizarov circular external fixator to obtain a ligamentotaxis reduction, following which the depressed subtalar joint fragments are elevated open; then, the fixator is used to reduce the lateral translation. All displacements of the fracture fragments are corrected. This method proved successful in six patients, all of whom achieved a satisfactory result with anatomic restoration of the subtalar joint and heel. One patient went on to late partial collapse of the posterior facet. Subtalar motion was greater than 50% in four of seven patients. None of the patients complained of heel pad pain, which was attributed to the desensitization of the heel by early weight bearing. This technique has produced encouraging preliminary results in two- to four-year follow-up evaluation. PMID- 8472440 TI - Two-stage operative treatment of comminuted os calcis fractures. Primary indirect reduction with medial external fixation and delayed lateral plate fixation. AB - The indication for otherwise established lateral plate fixation in fractures of the calcaneus becomes relative when severe comminution (Sander's Type III and IV) of the bone involves concomitant massive soft-tissue swelling. The calcaneus is shortened, Bohler's angle flattened, and lateral bulging and varus deformity persist throughout the six or more days needed for soft-tissue compromise to recede. Intraoperatively, problems with anatomic reduction are encountered primarily because of soft-tissue shrinkage and muscle contraction, underscoring the rationale for conservative treatment modalities. A two-stage approach- primary medial external fixation and delayed lateral plate fixation--stabilizes the calcaneus in a nearly anatomic position by calculated distraction through medial external fixation, leaving joint congruency to be restored in a secondary procedure, when soft tissues pose no problem for a lateral approach. The two stage procedure was used in 13 of 49 cases, in which soft-tissue compromise was severe. Anatomic primary reduction greatly facilitated delayed lateral plate fixation. Infection rates were not traced to the external fixation. Massive bone grafting was associated with a high occurrence of complications. PMID- 8472441 TI - Compartment syndromes of the foot after calcaneal fractures. AB - Approximately 10% of calcaneal fractures develop compartment syndromes of the foot, and of these, one half develop clawing of the lesser toes and other foot deformities, including stiffness and neurovascular dysfunction. Tense swelling and severe pain are the hallmarks of an impending compartment syndrome. The diagnosis is confirmed by multistick invasive catheterization, particularly of the calcaneal compartment in the hindfoot. Immediate fasciotomy is recommended to prevent the development of ischemic contracture. It is recommended that open reduction and internal fixation of a calcaneal fracture is performed on a delayed basis, after the fasciotomy wounds are closed. PMID- 8472442 TI - The management of soft-tissue problems associated with calcaneal fractures. AB - Soft-tissue problems associated with fractures of the calcaneus are common and can present many pitfalls. A classification of soft-tissue problems has been devised to facilitate treatment: Type 1, closed fractures treated by open reduction and internal fixation with an inability to close the skin. Type 2, wound break down after open reduction. Type 3, open fractures of the calcaneus with traumatic large soft-tissue loss but with adequate bone stock. Type 4, traumatic loss of soft tissue and bone. Type 5, calcaneal osteomyelitis. Type 6, chronic unstable soft tissue over the calcaneus. There are various surgical options of skin graft, rotational flaps, and free-tissue transfers that best reconstruct each of these individual problems. PMID- 8472443 TI - Reconstructive osteotomy of the calcaneus with subtalar arthrodesis for malunited calcaneal fractures. AB - A technique of dealing with the late complications of malunited calcaneal fractures is based on the philosophy of reversing the deformity associated with late complications. The primary fracture is a shearing fracture that runs obliquely down the length of the calcaneus from superolateral to inferomedial and anterolateral to posteromedial. This permits the tuberosity of the calcaneus to translate laterally and proximally, and often splits the posterior facet. The complications of malunion are loss of height of the heel with concomitant dorsiflexion of the talus, widening of the heel, lateral impingement of the peroneal tendons and the distal fibula, and subtalar posttraumatic arthritis. The primary fracture deformity contributes directly to the late complications. The reconstructive osteotomy recreates the primary fracture. This permits repositioning of the tuberosity that narrows the heel, alleviates impingement, and returns height to the heel. The subtalar arthrodesis alleviates the symptoms of posttraumatic arthritis. The reconstruction is not dependent on cortical bone grafts for stability. The clinical series involved ten feet with an average follow-up period of 14 months. Two were revisions of previous triple arthrodeses. Results were satisfactory in nine feet. PMID- 8472444 TI - Parosteal (juxtacortical) chondrosarcoma of the humerus associated with regional lymph node metastasis. A case report. AB - Recurring parosteal (juxtacortical) chondrosarcoma of the humerus occurred in a 79-year-old man. Roentgenograms of the left humerus showed minimal cortical irregularity and a large soft tissue mass without calcification or periosteal reaction. Magnetic resonance imaging (MRI) showed a multilobular tumor of high intensity (T2-weighted imaging) without marrow involvement. During the left shoulder disarticulation an enlarged axillary lymph nodes was discovered and removed. Macroscopic examination of the disarticulated humerus showed a large yellow parosteal mass, which looked like cartilage, completely surrounding the humeral shaft. The marrow cavity was almost normal except for a small erosion at the site of the olecranon fossa. The histologic diagnosis of the mass was Grade 2 chondrosarcoma of parosteal (juxtacortical or periosteal) origin associated with regional lymph node metastasis. The features that made this case unique were a long history of the tumor (for 32 years), minimal cortical destruction of the bone by the tumor, and regional lymph node metastasis. This case illustrates the differential diagnosis of the parosteal chondrosarcoma from periosteal osteosarcoma and extraskeletal myxoid chondrosarcoma. PMID- 8472445 TI - Biomechanics of the subtalar joint complex. AB - The subtalar joint complex is formed by the posterior talocalcaneal joint and the acetabulum pedis lodging the talar head. The basic motion at the joint is that of male ovoid surfaces moving over female ovoid surfaces and vice versa. The motion generated at the joint is that of flexion-supination-adduction or extension pronation-abduction. The subtalar motion is generated by the contour and orientation of the articular surfaces and is guided by the intrinsic ligaments: the interosseous talocalcaneal ligament of the canalis tarsi and the cervical ligament. Further support is provided by the extrinsic ligaments: the calcaneofibular ligament and the tibiocalcaneal fascicle of the deltoid ligament. Under tibiotalar vertical loading with internal rotation, the subtalar joint complex is in a close-pack position with maximum talar head surface contact in the acetabulum pedis. The component ligaments of the latter are under maximum tension. The posterior talocalcaneal surfaces are interlocked laterally. PMID- 8472446 TI - Arthroscopic subacromial decompression versus open acromioplasty. A two-year follow-up study. AB - In a prospective study, 20 patients were randomly selected for either open acromioplasty according to Neer or for arthroscopic subacromial + decompression (ASD). All suffered from shoulder impingement for which conservative treatment had been unsuccessful. Functional results after two years were assessed. All patients were assessed radiographically to visualize recurrence of subacromial osteophytes. Functional results in the arthroscopic group are good and similar to those after open surgery. Both methods seem to result in adequate subacromial decompression, including bone resection. The arthroscopic method also has in its favor less operating time, earlier restoration of active range of motion, and reduction in time away from work. PMID- 8472447 TI - Total elbow arthroplasty. An 18-year experience. AB - In 34 primary and 18 revision total elbow arthroplasties (TEAs), rheumatoid arthritis (RA) was the most common indication, with traumatic arthritis next most common. The indications were primarily pain and decreased range of motion. Follow up time averaged 7.6 years for index arthroplasties. Complication rates of primary arthroplasties were high, with 40% neural problems, 9.3% aseptic loosening, and 13.3% early postoperative infection. Overall function was satisfactory in 68% of patients with RA. In agreement, the rates of revision were high. Overall satisfaction was good, and function was fair in patients with TEA. PMID- 8472448 TI - A comparison of femoral neck fixation with the reconstruction nail versus cancellous screws in anatomic specimens. AB - Femoral neck fixation techniques were applied to five matched pairs of autopsy specimens to evaluate the fixation of the Russell-Taylor femoral nail in ipsilateral neck and shaft fractures of the femur. Reconstruction nail fixation of the femoral neck was compared with that of three parallel screws. The intact and postfixation femora were subjected to an applied bending moment in 0 degrees, 30 degrees, and 90 degrees of simulated hip flexion. The bending stiffness was determined from the load deformation data for each intact femur and then after the appropriate fixation. The fatigue response of the fixation, presence of osteopenia, degree of fracture reduction, and device alignment showed that the stiffness ratio (fixed to normal) of the nail was greater in most specimens. There was no statistical difference in retained stiffness after cyclic loading between the nail and cancellous screw fixations. The ultimate strength of the nail was 2.5 times the strength of the screw fixation of the femoral neck. Thus, the nail provided biomechanically sound fixation of the femoral neck. PMID- 8472449 TI - Total hip arthroplasty in juvenile rheumatoid arthritis. AB - A series of 17 primary total hip arthroplasties in patients with juvenile rheumatoid arthritis (JRA) were performed at a mean age of 18 years with an average follow-up period of 9.3 years. There were 13 cemented prostheses and four noncemented. All patients were satisfied with their hip surgery and reported either slight or no hip pain according to the Harris hip rating system. Ambulation improved postoperatively and all but one patient was at least a limited community ambulator (able to ambulate short distances outside the home with crutches, walker, or cane). Roentgenogram evaluation showed five cemented hips that were believed to be definitely loose with impending failure. All were functioning well. One acetabular component has been revised to date. No femoral components have been revised. The four noncemented hips with an average follow-up period of five years were functioning well. PMID- 8472450 TI - Avascular necrosis of the femoral head in sickle cell disease. An integrated classification. AB - Avascular necrosis of the femoral head (ANFH) is one of the crippling complications of sickle cell disease (SCD), and to date there is no classification that could identify patients in the early phase of the necrosis. Based on the experience of 66 ANFH in 43 patients with SC hemoglobinopathy, the necrosed hips were classified into four grades, Grade I to Grave IV, based on patient history, clinical evaluation, and radiologic examination. In Grade I, the patient complains of the mildest symptoms with minimal clinical signs and radiologic changes. The most severe form, Grade IV, is where the findings are unbearable pain with disability and marked roentgenographic evidence of osteonecrosis. This classification identifies patients in Grade I and II, which, with early diagnosis and proper management, could delay further deterioration of the necrosed femoral head. PMID- 8472451 TI - Role of mesenchymal collagenase in the loosening of total hip prosthesis. AB - Fibroblast-type interstitial collagenase (E.C. 3.4.24.7) was associated with loosening of total hip prostheses in eight patients: there were four cemented stems and one cementless stem with the common type of loosening and two cemented stems and one cementless acetabular component with aggressive granulomatous lesions. The authors used a specific, well-characterized, heterologous, affinity purified, polyclonal rabbit anti-human fibroblast collagenase antiserum applied in avidin-biotin-peroxidase-complex (ABC) staining. In the aggressive granulomatous type of loosening, collagenase was found in most of the fibroblast- and macrophagelike cells, including multinuclear giant cells and epithelioid cells in periprosthetic tissue. Collagenase-positive cells also were found in the periprosthetic tissue associated with common loosening. Collagenase was also found in capillary and postcapillary venule endothelial cells in the richly vascularized aggressive granulomatous tissue. Collagenase was extracted directly from the tissue samples and incubated with soluble Type I collagen. Collagen degradation products then were analyzed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, and the three-fourths length degradation product quantitated by gel scanning densitometry. In both aggressive granulomatosis and the common type of loosening, extractable collagenase was found in tissue. No significant differences between the sample groups were detected in respect to total measurable collagenase, however. The extractable collagenase was present in a latent form that could be activated by the organomercurial procollagenase activator, phenylmercuric chloride (PMC). It is likely that interstitial collagenase contributes to rapid growth of reactive infiltrative tissue, loosening of the prosthesis associated with aggressive granulomatosis, and the periprosthetic lytic process associated with the common type of hip prosthesis loosening. PMID- 8472452 TI - Dialysis arthropathy of the hip. AB - Beta 2-microglobulin amyloid deposition is associated with a destructive arthropathy in the hip of chronic hemodialysis patients. Twenty-five hips from 18 patients were assessed for the presence and immunohistochemical type of amyloid. The hemodialysis group was compared with an age- and disease-matched control group that had no evidence of renal failure. Beta 2-microglobulin amyloid deposits were present in all patients who had been on hemodialysis for 18 months or more. Beta 2-microglobulin amyloid deposits were not found in patients who had been on hemodialysis for less than 18 months. Amyloid deposits were seen first in the articular cartilage and later involved the synovial membrane, joint capsule, and subchondral bone as well. The presence and amount of amyloid deposition correlated to the duration of hemodialysis. Severely affected hip roentgenographically had a concentric loss of joint space, periarticular erosions, and cystic lesions in the femoral head and acetabulum. These pathologic and roentgenographic changes suggest that amyloid deposition leads directly to the erosive hip arthropathy occurring in hemodialysis patients. PMID- 8472453 TI - Cemented acetabular reconstruction with the Muller support ring. A minimum five year clinical and roentgenographic follow-up study. AB - In a previous study, the results of cemented acetabular reconstruction with a Muller support ring were reported after a mean follow-up period of 40 months. The current report concerns a minimum five-year follow-up study of the same 43 patients. Two early failures at four months and at 17 months were related to poor surgical technique. The latest overall functional results, according to the Merle d'Aubigne rating scale, were excellent, very good, or good in 81.82% of the hips: a drop from 86.67% since the previous report. Sequential roentgenographic analysis demonstrated a high incidence of nonprogressive radiolucencies at the cement-bone interface. These nonprogressive radiolucencies did not correlate with the overall functional results. The progression of a radiolucency at the cement bone interface, however, or the appearance of radiolucencies around the screw threads, always resulted in clinical failure. PMID- 8472454 TI - Contribution of rectus femoris and vasti to knee extension. An electromyographic study. AB - Electromyographic (EMG) activity was recorded from the five components of the quadriceps during maximum knee extension with the limb in six combinations of hip and knee flexion: the hip at 0 degrees, 40 degrees, and 80 degrees with the knee at 15 degrees and 60 degrees. None of the six positions could isolate the vasti from the rectus femoris. The highest EMG activity of all five muscles was recorded with the limb in 40 degrees hip flexion and 15 degrees knee flexion. The lowest EMG activity was recorded with the hip at 0 degrees and the knee at 60 degrees flexion. Overall, the knee extension torques were 40% higher with the knee at 60 degrees flexion than at 15 degrees flexion. The lowest torques were generated with the limb positioned at 80 degrees hip flexion and 15 degrees knee flexion. During maximum knee extension, the vasti muscles do not work in isolation of the rectus femoris, regardless of the amount of hip flexion. All portions of the quadriceps worked in all positions, which suggests these muscles may be strengthened effectively in many different positions to accommodate the patient's comfort and interest. PMID- 8472455 TI - Difficulties with bearing dislocation and breakage using a movable bearing total knee replacement system. AB - In 1980, the low contact stress, or New Jersey, system was introduced with movable high-density polyethylene bearings between the metallic femoral and tibial components. This system was developed to deal with two principal concerns of conventional knee replacement systems: loosening and wear. A federal Drug Administration review was required, and the study was performed in two phases. From 1981 until 1984, components were cemented in 40 knees, which then were evaluated for an average of seven years after surgery. From 1984 until 1986, 16 knees were selected for cementless fixation and were followed for an average of five years. The cemented group had a failure rate of 10% (four knees), two from tibial component loosening, one from bearing dislocation, and one from infection. Failure was determined by the necessity for revision. The uncemented group had a failure rate of 31% (four knees from bearing fracture and one from knee pain of uncertain source). Bearing failure was attributable to the entrapment of the subluxed lateral bearing. Sacrifice of the anterior cruciate ligament predisposes the system to bearing subluxation and failure. PMID- 8472456 TI - Long-term follow-up study on the Maquet procedure with special reference to the causes of failure. AB - Thirty-nine patients with symptomatic osteoarthrosis (OA) of the patellofemoral joint were treated with 42 anterior tibial tubercle elevations, also known as the Maquet procedure. The patients all had symptomatic OA of the patellofemoral joint that fell into one of three categories: old patellar fracture, chronic patellar subluxation, or postpatellectomy pain. In the latter group, the OA was manifested by erosions of trochlear articular cartilage from the articulating quadriceps tendon-patellar ligament suture line. All 39 patients had a 1.5-2.5-cm tibial tubercle elevation with medial displacement, as necessary, to centralize their patellofemoral mechanisms. Follow-up period averaged 6.1 years. Seventy-nine percent (33 of 42 procedures) had good to excellent results. There was a major complication rate of 7%. Six of the nine failures were attributable to social/psychiatric reasons. Previously unrecognized tibiofemoral OA was the reason for poor results in two of the other failures, and one failure was unexplained. Patients with long-standing symptoms caused by patellofemoral OA should preoperatively be psychologically evaluated and diagnostically arthroscoped before the Maquet procedure is carried out. PMID- 8472457 TI - The axes of rotation of the knee. AB - Knee motion is believed to occur about a variable flexion-extension (FE) axis perpendicular to the sagittal plane and a longitudinal rotation (LR) axis. The authors used a mechanical device to locate the FE and the LR axes of six fresh anatomic specimen knees. The motion of points on the LR axis produced circular, planar paths about the fixed FE axis. Magnetic resonance (MR) images in planes perpendicular to the FE axis showed a circular profile for the femoral condyles. The FE axis is constant and directed from anterosuperior on the medial side to posteroinferior on the lateral side, passing through the origins of the medial and lateral collateral ligaments and superior to the crossing point of the cruciates. The LR axis is anterior and not perpendicular to the FE axis, the anatomic planes. This offset produces the valgus and external rotation observed with extension. The implications of two fixed offset axes for knee motion on prosthetic design, braces, gait analysis, and reconstructive surgery are profound. PMID- 8472458 TI - Treatment of complex tibial shaft fractures. Arguments for early secondary intramedullary nailing. AB - In 135 cases of mainly open tibial shaft fractures treated primarily with external fixation, 73 patients (54%) were treated exclusively with external fixation; osteomyelitis occurred in 8.2%, nonunion in 8.2%, and malunion in 32.8%. Later sequential plating was performed in 38 patients (28%), and in 24 patients (18%) secondary intramedullary nailing. Patients with delayed nailing after primary external fixation had the lowest incidence of osseous infection (4.1%) and nonunion (4.1%), the lowest malunion rates under strict criteria (24%), and a significantly shorter healing time (21.5 weeks versus 33.4 weeks after secondary plating and 30.2 weeks after treatment with external fixation alone). Patients treated with secondary plating had osseous infection in 10.2%, nonunion in 7.8%, and malunion in 29.3%. Changing to an intramedullary nail after primary treatment of open tibial shaft fractures with external fixation was a more effective way to treat these fractures than definitive treatment with external fixation alone or delayed secondary treatment by plating. Sequential nailing can be performed as early as one to three weeks after trauma without the necessity of a safety interval between the removal of external fixation and intramedullary nailing to prevent infection. PMID- 8472459 TI - Anatomy of the calcaneus. AB - The calcaneus is the largest tarsal bone in the foot and is well designed to sustain high tensile, bending, and compressive forces. However, high instantaneous loads often result in fracture. Any treatment of calcaneal fractures requires a working knowledge of the anatomy. The major neurovascular structures are located medially and are well insulated by the medial soft tissues. These structures are at risk, however, during medial approaches to the calcaneus. Laterally, there are several bony landmarks that are palpable primarily because of the relative paucity of the soft-tissue elements. Lateral approaches to the calcaneus have been associated with the areas of skin necrosis that may be related to the arterial anatomy. The calcaneus has four articular surfaces. The congruity of these articular surfaces and their relationship to one another can be assessed roentgenographically. With adequate knowledge of the bony anatomy of the calcaneus and its soft tissue envelope, a rational approach in assessment and treatment of calcaneal fractures can be developed. PMID- 8472460 TI - Complicated removal of the distal locking device of Brooker-Wills. AB - Fractures of the femur in two women, ages 17 and 27, were treated with Brooker Wills nails. While the distal deployment device was inserted into the nail in one patient, the tip of the driver/inserter broke into the proximal end of the distal deployment device. This complicated the extraction of the nail and the distal locking device after healing of the fracture. In the other patient, removal of the distal locking device and the nail was complicated by inability to engage the tip of the driver inserter into the proximal end of the distal deployment device. The method described here facilitates removal of nails and the distal locks. PMID- 8472461 TI - The effects of freeze-drying and rehydration on cancellous bone. AB - Processing technique significantly affects the strength and stiffness of bone for use as a structural alloimplant in reconstructive surgery. The effects of the rehydration of freeze-dried human cancellous bone were studied using 14-mm diameter cancellous dowels taken from matched cadaveric sites. Three different methods of rehydration were evaluated and compared with unrehydrated freeze-dried and frozen grafts. All samples were biomechanically tested in anatomically matched pair groups to determine compressive strength and stiffness. The strength of each tested graft was expressed as a percentage of its matched pair control. Freeze-dried grafts rehydrated for 24 hours compared with frozen grafts showed no significant difference in mean compressive strength (92.6% +/- 13.3% of control). Analysis of in vacuo versus ex vacuo rehydration at one hour showed a 38% greater mean compressive strength and a 42% greater mean stiffness for the ex vacuo group. Unrehydrated grafts appeared to be both stronger and stiffer than their rehydrated counterparts. These results suggest that the rehydration of freeze dried grafts may adversely affect graft strength and stiffness. Rehydration under a negative pressure may proceed more rapidly than the process at atmospheric pressures. These findings limit the acceptability of freeze-dried grafts as structural implants. PMID- 8472462 TI - A biomechanical analysis of atlantoaxial stabilization methods using a bovine model. C1/C2 fixation analysis. AB - The reliability and initial postoperative stability of six widely used C1-C2 surgical constructs were evaluated by nondestructive biomechanical testing of ten fresh bovine upper cervical spine segments. The six fixation techniques were the simple midline sublaminar C1 wiring (SMW), the modified Gallie wiring (MGW), the Brook wedge arthrodesis (BWA), the bilateral lateral mass screw (LMS), and the Clark arthrodesis without (CWO) and with (CW) the adjunctive use of polymethylmethacrylate (PMMA) cement. Instability was produced by resection of the base of the dens. Intact, destabilized, and instrumented constructs were tested in unconstrained flexion, extension, torsion, anterior, and posterior shear forces. The LMS and CW techniques proved the most effective in achieving C1 C2 stability. Sublaminar C2 wiring methods tended to have greater torsional and shear stiffness. Less rigid fixation techniques frequently loosened. All non-PMMA enhanced wired constructs failed to restore the ability to adequately resist the posterior translation of C1 on C2. Stabilization of an unstable atlantoaxial articulation is best accomplished by a lateral mass screw or sublaminar C1-C2 PMMA-enhanced technique. Other techniques provided less consistent and reliable surgical fixation. Because of the inadequacy of wired constructs to resist posterior shear in patients with this instability pattern, the usual treatment may need to be modified to include more prolonged or protective external immobilization or more rigid fixation techniques. Although less rigid, the SMW and the MGW techniques are safer because they require less-frequent passage of sublaminar wires, avoid potential problems with PMMA, and obviate the hazards of further lateral dissection and insertion of the transarticular screws. PMID- 8472463 TI - Osteoinductive activity of composites of bone morphogenetic protein and pure titanium. AB - Titanium sponges were infused with bone morphogenetic protein (BMP-Ti), and the osteoinductivity of the resultant composite was measured. New bone formation occurred three weeks after implantation and was identified by soft x-ray analysis. Quantitative analysis showed no significant difference between BMP-Ti composites and control samples (BMP only). Consequently, pure titanium neither inhibited nor promoted BMP activity. Chondrocytes and new bone formation occurred in direct contact with the surfaces of the titanium. X-ray microanalysis demonstrated new bone formation inside the pores of the titanium sponges. The BMP Ti composite has interesting properties as an osteoinductive implant and has potential practical clinical applications. PMID- 8472464 TI - The mechanism, reduction technique, and results in fractures of the os calcis, 1951-52. PMID- 8472465 TI - International documentation and evaluation system. PMID- 8472466 TI - Osteoarthritis/osteoarthrosis. PMID- 8472467 TI - A common problem with cementless femoral components. PMID- 8472468 TI - Mechanism and pathoanatomy of the intraarticular calcaneal fracture. AB - The mechanism and pathoanatomy of the acute intraarticular calcaneal fracture is produced by axial loading. A combination of shear and compression forces produce two characteristic primary fracture lines. Shearing forces produce a fracture dividing the calcaneus into medial and lateral portions. This fracture line typically splits the posterior facet and can extend anteriorly to involve the anterior and cuboid facets. Compression forces divide the calcaneus into anterior and posterior portions. This fracture line can extend medially to involve the middle facet. Loss of calcaneal height and length are readily explained by this mechanism. PMID- 8472469 TI - The radiologic evaluation of calcaneal fractures. AB - Although computed tomography (CT) scanning has revolutionized the treatment of calcaneal fractures, simple studies such as Bohler's view still have a role in the diagnosis and management of these fractures. This article reviews the benefits and limitations of these imaging techniques for calcaneal fractures. PMID- 8472470 TI - Intraarticular calcaneal fractures. Results of closed treatment. AB - Thirty intraarticular calcaneal fractures were studied by computed tomography and then treated with a variety of closed methods. A classification of the fractures was devised according to the amount of displacement of the posterior facet. Follow-up evaluation showed that Type I fractures recovered function and healed extremely well. Closed treatment should be the treatment of choice for Type I fracture patterns. Type II and III fractures had unacceptable results with closed treatment. Alternate forms of treatment should be considered in dealing with more severely displaced fractures. PMID- 8472471 TI - The operative treatment of intraarticular calcaneal fractures. Indications, technique, and results in 257 cases. AB - Since 1972, 257 intraarticular fractures of the calcaneus have been treated with operative intervention. A lateral incision and a third tubular plate were used in all cases. The functional results were considered excellent or good in 85%, and there was an infection rate of 2.7%. Although 50% of patients showed a reduced mobility of the subtalar joint, pain and limited ambulation were rare. Only six patients required a late subtalar arthrodesis. PMID- 8472472 TI - Open treatment of acute calcaneal fractures. AB - Displaced intraarticular fractures of the calcaneus require operative intervention to restore the anatomy of the bone, which in turn is the requirement for recovery of subtalar joint mobility. Surgery through a lateral incision, without opening the sheath of the peroneal tendons, and the use of lag screws and a "Y-plate," must restore not only the respective positions of the "three poles" of the calcaneus but also the respective orientations of the articular surfaces. Stable internal fixation allows early active and passive mobilization of the subtalar and ankle joints. If this is not achieved, the functional outcome will be poor. PMID- 8472473 TI - Surgical treatment of displaced intraarticular fractures of the calcaneus. A combined lateral and medial approach. AB - Twenty-two patients with 22 displaced intraarticular fractures of the calcaneus were treated by open reduction and internal fixation using a lateral approach and, when needed, a medial approach, followed by early motion. These patients were evaluated from 16 to 72 months (average, 37 months) after surgery. At follow up evaluation, the result was assessed on the basis of restoration of anatomy and function. Combining the anatomic and functional findings, the results in this series were good in 17 patients, fair in one, and poor in four. PMID- 8472474 TI - Osteosynthesis of displaced intraarticular fractures of the calcaneus. Results in 123 cases. AB - The operative treatment of intraarticular calcaneal fractures has three principal aims: restoration of height, length, and width of the calcaneus, reconstruction of the subtalar and calcaneocuboid joint surfaces, and stable osteosynthesis using an H-plate or screws. In 68% of the cases, the sustentacular fragment was the key to open reduction, making the medial approach mandatory. In complex fractures, a lateral approach is added. In "blow-out" fractures or cases with comminution of the sustentacular fragment, an extended lateral approach only is used. For precise preoperative planning of roentgenograms in three planes, four Broden's views and axial plus coroneal or three-dimensional computed tomography scans are required. From July 1983 to July 1990, 157 intraarticular calcaneal fractures were treated by open reduction. The results in 123 cases are 61% good or excellent, 32.5% satisfactory, and 6.5% poor. The following early complications occurred: superficial wound edge necrosis (8.3%), hematoma (2.5%), nonunion (1.3%), and infection (1.9%). Four patients (3.3%) in the follow-up group have developed degenerative changes severe enough to require subtalar fusion. To facilitate the comparison of results, new fracture classification and follow-up scoring systems have been devised. PMID- 8472475 TI - Operative treatment in 120 displaced intraarticular calcaneal fractures. Results using a prognostic computed tomography scan classification. AB - From January 1987 to September 1990, 132 displaced intraarticular calcaneal fractures were treated operatively using a lateral approach, lag screws, and side plate without bone graft. To evaluate the results, a classification for intraarticular calcaneal fractures was developed, based on standardized coronal and transverse computed tomography (CT) scans of both feet. Type 1 fractures were nondisplaced (and received nonoperative treatment); Type II were two-part or split fractures; Type III were three-part or split depression fractures; and Type IV were four-part or highly comminuted articular fractures. Results were evaluated using the Maryland Foot Score and repeat CT scans. One hundred twenty cases were available for a minimum of one year follow-up evaluation (range, 12-56 months; mean, 29.3 months). Roentgenographic evaluation of calcaneal body dimensions showed restoration of heel height (98%), width (110%), and length (100%) to virtually normal in all cases, regardless of preoperative displacement. Roentgenographically, articular reduction was anatomic in 68 of 79 (86%) Type II fractures, 18 of 30 (60%) Type III fractures, and 0 of 11 (0%) Type IV fractures. Excellent or good clinical results occurred in 58 of 79 (73%) Type II fractures, 21 of 30 (70%) Type III fractures, and one of 11 (9%) Type IV fractures. When excellent and good clinical results were compared by year, a distinct learning curve appeared (1987, 27%; 1988, 54%; 1989, 74%; 1990, 84%). Despite an improved outcome for Type II and III fractures with increasing surgical experience, the results of operative intervention in Type IV fractures were no better, even after four years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472476 TI - The medical approach for calcaneal fractures. AB - A practical classification of calcaneus fractures based on standard heel roentgenograms and Broden's views is presented. Diagnosis is made from these roentgenograms, even though many believe that more sophisticated studies are needed. In fact, only the Broden's and lateral views are needed for diagnosis. What one needs to know is the type of fracture present, whether it is a tongue or joint depression-type fracture, and the width of the fragment. The necessary information is easily determined from these roentgenograms. Once these facts are known, a plan of approach can be made. The medial approach is an indirect method of reduction as one might use for the tibia or femur fracture. Experience has shown that the longitudinal threaded pin is an excellent method of stabilization. It is quick and effective. It has eliminated the need for exposure of the neurovascular bundle. Minimal metal is implanted, and a smaller incision is used. Most common calcaneal fractures can be reduced well from the medial side. A few may need lateral reduction also, but this is simplified if the nonarticular components of the fracture are reduced first by the medial approach technique. The results of the medial approach technique have been much better in the last 12 years. This is attributed to the classification, the knowledgeable interpretation of the roentgenograms, and use of the threaded longitudinal pin for fixation. PMID- 8472477 TI - Acute pulmonary complications in immunocompromised non-AIDS patients: comparison of diagnostic accuracy of CT and chest radiography. AB - To compare the abilities of computed tomography (CT) and radiography in detection and diagnosis of acute pulmonary complications in immunocompromised non-AIDS patients, the CT scans and radiographs of 45 immunocompromised non-AIDS patients with proven pulmonary disease and 20 normal controls were independently assessed by two observers, without knowledge of clinical or pathologic data. The observers listed the three most likely diagnoses and their degree of confidence in the first-choice diagnosis on a three-point scale. The sensitivity and specificity in detecting pulmonary complications was 100% and 98% for CT, compared to 98% and 93%, respectively, for chest radiography. In the immunocompromised patients, the first-choice diagnosis was correct in 44% of CT and 30% of radiograph readings (P < 0.01). The correct diagnosis was among the top three diagnoses in 70% of CT scans and 53% of radiograph readings (P < 0.01). Confidence level one (definite) was reached in 33% of CT scans and 10% of chest radiographs (P < 0.001). Diseases with a dominant nodular pattern had a higher occurrence of correct first-choice diagnosis (62% vs 34%, P < 0.02) and level one confidence ratings (53% vs 13%, P < 0.001) than diseases with ground-glass opacity, consolidation or irregular linear opacities. We conclude that chest radiographs and CT scans have comparable sensitivity in detecting acute pulmonary complications in immunocompromised non AIDS patients. CT is superior to chest radiography in the differential diagnosis of acute pulmonary complications in these patients. PMID- 8472478 TI - The prevalence of paranasal sinus disease in HIV infection and AIDS on cranial MR imaging. AB - Sinusitis poses a difficult clinical challenge in the management of patients with AIDS because of high rates of relapse and the association with unusual pathogens. To determine the prevalence and severity of sinus disease in this group we prospectively analysed the condition of the paranasal sinuses shown on cranial MR scans of 156 patients referred for the investigation of suspected intracranial pathologies. These included 104 HIV seropositive patients, including 93 with an AIDS-defining diagnosis (CDC IV). Forty-two scans were performed on age-matched controls. The scans were timed to control for seasonal variations in sinus disease and were interpreted by two radiologists who were blinded to the clinical and serological status of the patients. Severe mucosal disease (more than one sinus showing > 75% obliteration) or moderate mucosal disease (only one sinus showing > 75% obliteration) was seen in 15.1% (14/93) patients with AIDS and none of the 42 controls (chi 2 = 6.73, P < 0.01). The mean maximum mucosal thickness in patients with AIDS was significantly greater than the control group (P < 0.001) and also significantly greater than in seropositive patients who had not had an AIDS-defining diagnosis (CDC II/III) (P = 0.006). Paranasal sinus mucosal abnormalities seen on MRI are greater in prevalence and severity in patients with AIDS and about one in seven would be expected to have at least one sinus largely obliterated. PMID- 8472479 TI - Ablation of mediastinal parathyroid adenomas by superselective embolization of the internal mammary artery with alcohol. AB - Two young patients (20 and 21 years) had recurrent hyperparathyroidism following neck exploration. Non-invasive investigations failed to localize a parathyroid adenoma. In both cases selective catheterization of the internal mammary arteries combined with digital angiography demonstrated hypervascular mediastinal adenomas. Using a coaxial catheterization technique (Tracker 18 and 10), both branch arteries of the internal mammary supplying the adenoma were selectively catheterized. In one case absolute alcohol and the other a mixture of Lipiodol and absolute alcohol were used to effect the ablation. The procedures were uneventful and serum calcium levels have subsequently returned to within normal limits. The follow-up in these two cases extends to 2 1/2 years in one and 10 months in the other case. PMID- 8472480 TI - Duplex Doppler detection of hepatic artery thrombosis following liver transplantation. AB - Hepatic artery thrombosis is a major cause of morbidity and mortality following liver transplantation. We assessed the value of prospective duplex Doppler ultrasound in detecting hepatic artery thrombosis. One hundred consecutive transplants in 90 patients were studied. Duplex Doppler detected all 10 proven cases of hepatic artery thrombosis. No case of hepatic artery thrombosis was found with a normal duplex study. All arteriograms performed following an abnormal ultrasound demonstrated hepatic arterial occlusion or anastomotic stenosis or a segment of irregular arterial narrowing. We conclude that duplex Doppler is a practical and sensitive method of selecting patients with a presumptive diagnosis of hepatic artery thrombosis for further investigation by angiography. PMID- 8472481 TI - Phase III trial of oral magnetic particles in MRI of abdomen and pelvis. AB - A prospective Phase III trial was performed to evaluate the efficacy in clinical practice of a new gastro-intestinal contrast agent, Oral Magnetic Particles (OMP), for use in abdominal and pelvic magnetic resonance imaging (MRI). This was an open study comprising 35 patients each given 800 ml of OMP at a concentration of 0.5 g/l. Distribution of the agent was most reliable in the small bowel. General contrast effect was satisfactory, and image quality and diagnostic confidence were enhanced. Administration of OMP increased diagnostic information in the magnetic resonance (MR) image in 50% of patients. No clinically significant adverse effects were observed. The results confirm in a clinical setting a potential role for this new contrast agent. PMID- 8472482 TI - Balloon-expandable intravascular stents in atherosclerotic iliac artery stenosis: preliminary experience. AB - Ten patients with symptomatic iliac artery stenosis underwent percutaneous insertion of balloon-expandable intravascular stents. A total of 12 stents were inserted in the common iliac (7 patients) and external iliac (3 patients) arteries. The indications for placement were unsuccessful angioplasty (5 cases), to improve inflow prior to a subsequent distal bypass graft (3 cases) and localized iliac disease in patients deemed unfit for aorto-femoral by-pass surgery (2 cases). Of the 10 patients, five had rest pain and five had severe intermittent claudication at distances varying from 25 to 75 yards, prior to the procedure. Ankle-Arm Doppler systolic pressure indices increased from a mean of 0.61 to 0.91 post procedure. Eight of the 10 patients are asymptomatic at follow up, average 12 months (range 8-18 months). One patient died from an unrelated cause and the other patient remains symptomatic due to distal disease (Table 1). Our experience suggests that percutaneous insertion of balloon-expandable intravascular stents is a valuable technique for treatment of external and common iliac stenosis. PMID- 8472483 TI - Transpopliteal angioplasty of combined iliofemoral occlusions. AB - We report two cases of iliofemoral occlusive vascular disease which were successfully treated by angioplasty via the popliteal artery. The merits of this approach, when ipsilateral femoral puncture is precluded, are discussed. PMID- 8472484 TI - Computed tomography of vertebral tuberculosis: patterns of bone destruction. AB - A retrospective analysis was performed of CT scans of 30 consecutive patients with a clinical suspicion or diagnosis of spinal tuberculosis. Four patterns of bone destruction were noted, namely, fragmentary, osteolytic, subperiosteal and well-defined lytic with sclerotic margins. The fragmentary type was most common (47%). Intervertebral disc destruction was always associated with contiguous vertebral body destruction. Associated paravertebral soft-tissue masses were seen in all patients. Epidural extension of disease was seen in 66% and showed a very good correlation with neurological signs on clinical evaluation. Bone fragments were detected in the epidural soft-tissue mass in 65% of patients with epidural extension of disease. CT appearances of bone destruction are highly suggestive of tuberculous osteomyelitis in about half the patients. PMID- 8472485 TI - Colonic sonography: preliminary observations. AB - Transrectal instillation of water is a recently described technique for improved sonological imaging of the lumen and wall of the colon. In order to assess the accuracy of this technique, termed colonic sonography (CS), in the detection of abnormalities of the large bowel, 100 consecutive patients were subjected to colonic sonography and the results were compared with the results of colonoscopy and surgery. The technique showed a sensitivity of 91% for the detection of colonic tuberculosis, 89% for ulcerative colitis and 83% for colonic cancers. Small mucosal ulcers, polyps less than 7 mm in diameter and the changes of non specific colitis were not detected. Sonography displayed the entire colon more consistently than colonoscopy. The extent and extra-colonic spread of disease were better appreciated. The procedure was not adversely influenced by the presence of faecal material within the colon and was well tolerated. Colonic sonography is a promising new technique for detecting significant colonic pathology and merits further comparison with existing modalities. PMID- 8472486 TI - Technical report: the Venflon 2 intravenous cannula used for arterial catheterization. AB - Using conventional guidewire techniques we have found the Venflon 2 (Viggo Spectramed) to be a safe and effective arteriographic puncture needle. The Venflon 2 offers significant technical advantages and cost savings when compared with traditional needles. Its use and limitations are discussed. PMID- 8472487 TI - Case report: sonographic detection of renal transplant cortical calcification. AB - Cortical calcification in a transplanted kidney was detected by high resolution ultrasound, not visible on plain abdominal radiography. Early recognition of these sonographic appearances should lead to a more accurate diagnosis and institution of appropriate treatment in patients with post-operative transplant dysfunction. PMID- 8472488 TI - Case report: accumulation of 99mTc-hydroxymethylene diphosphonate by liver metastases of prostatic adenocarcinoma. AB - We describe the case of a man with known prostatic carcinoma and bone metastases who was admitted with jaundice and hepatomegaly. A bone scan showed uptake of diphosphonate by the liver and ultrasound suggested the presence of diffuse metastatic disease. Liver biopsy revealed foci of carcinoma cells in the portal tracts which exhibited positive cytoplasmic staining for prostate-specific antigen, thus confirming the presence of metastatic prostatic adenocarcinoma. PMID- 8472489 TI - Case report: imaging of widespread plexiform neurofibromatosis. AB - Although the cutaneous, bony and retroperitoneal appearances of peripheral von Recklinghausen neurofibromatosis are well known, involvement of intra-abdominal organs and of the mediastinum is less well recognised. We present the case of a woman with peripheral neurofibromatosis who presented with loin pain. In addition to cutaneous neurofibromas, plexiform neurofibromas were present in the mediastinum, liver, mesentery and psoas muscles. PMID- 8472490 TI - Case report: radiological features of epidermal inclusion cyst of the tympanic membrane. AB - Computed tomography (CT) proved to be invaluable in diagnosing and ascertaining the extent of an epidermal inclusion cyst of the tympanic membrane secondary to a previous myringoplasty. PMID- 8472491 TI - Case report: pericolic abscess secondary to torsion of an appendix epiploica. AB - Torsion of the appendices epiploicae is a rare condition which may present with acute abdominal pain and mimic appendicitis. Untreated, peritonitis or intestinal obstruction may result. We present a case in which torsion of an appendix epiploica led to the development of a pericolic abscess communicating between the colon and lesser sac. To our knowledge these radiological findings have not been described previously. PMID- 8472492 TI - A pseudo body packer. PMID- 8472493 TI - Risks of diagnostic radiation. PMID- 8472494 TI - Bone marrow trephine biopsy: anterior superior iliac spine versus posterior superior iliac spine. AB - Bone marrow biopsy (BMB) is generally performed either on the anterior superior iliac spine (ASIS) or the posterior superior iliac spine (PSIS), the choice between these two sites depending largely upon practice at individual centres. No previous study has attempted to ascertain which of these two sites is preferable for needle BMB. We studied 72 biopsies, of which 36 were of the PSIS and 36 of the ASIS, measuring the length of the cylinder and the area of the histologic section. We asked those patients who had undergone BMB at both sites which had been the less painful. The cylinders obtained from the PSIS were found to have a significantly greater length and area than those obtained from the ASIS (P < 0.00001). Of the 13 patients who underwent BMB at both sites, 11 reported the PSIS biopsy to have been distinctly less painful (P = 0.012). We conclude that needle BMB of the PSIS provides samples of greater length and area, and is less painful, than that of the ASIS. PMID- 8472495 TI - A computerized expert system for handling the output of the Technicon H1 haematology analyser. AB - A computer-based expert system is described which handles the output of the Technicon H1 in the haematology laboratory of a large teaching hospital. Using patient request data, analyser results, error and morphology flags, the expert system decides; whether to validate the main indices plus differential; whether a blood film is required for manual review; and which abnormal results require phoning to the requesting doctor. The results of this computer-assisted analysis are sent to a printer adjacent to the analyser. The print-out details any further action required of the operator before release of results to the main hospital computer, and serves as a log of all samples run on that analyser. Benefits of the expert system include greatly simplified interpretation of the large array of analyser flags, and consistency in sample handling for all operators over all shifts. PMID- 8472496 TI - The effect of acidified glucose nutrient solution on preservation of platelet concentrate. AB - The preservation effect of a new platelet solution--acidified glucose nutrient solution (AGN)--was tested by adding AGN to pooled platelet rich plasma (PRP) prior to preparation of platelet concentrates (PC). Each PRP unit was prepared from a unit of whole blood and four PRP of the same blood group were pooled in 400 ml volume PVC bags. Equal aliquots of each pooled PRP were made prior to preparation of PC. AGN was added to one aliquot and nothing was added to the control aliquot. Equal volume and concentration PC were then prepared and the PC were further aliquoted for storage at 22 degrees C. After five days, the parameters of platelet count, pH, aggregability and hypotonic shock response (HSR) for PC preserved in AGN plasma were better than those of the controls preserved in normal ACD plasma. The aggregability and HSR of AGN platelet concentrates recovered to baseline after two h of incubation with fresh plasma. The results of electron microscopy show that platelets preserved in AGN have less changes in morphology. The results of our work suggest that the preservation effect of AGN on PC is similar to the effect of using second generation containers or preparation of platelets from thrombocytapheresis. PMID- 8472497 TI - Acute promyelocytic leukaemia following radioiodine therapy. PMID- 8472498 TI - Haemolytic transfusion reaction--successful attenuation with methylprednisolone and high dose immunoglobulin. PMID- 8472499 TI - The combination of hydroxyurea and leucapheresis in the treatment of chronic myeloid leukaemia in pregnancy. AB - Treatment of malignancy during pregnancy is difficult because of the potential teratogenicity of chemotherapeutic agents. Leucapheresis was employed in the initial management of a pregnant patient with chronic myeloid leukaemia. It was subsequently replaced with oral hydroxyurea during the second trimester. Successful delivery of a live male infant was achieved and the child has normal growth and development to date. PMID- 8472500 TI - Spontaneous remission of chronic pure red cell aplasia after failure of immunosuppressive therapy. PMID- 8472501 TI - Reference ranges for haematology parameters in pregnancy derived from patient populations. AB - Reference ranges for several haematology parameters in pregnancy were determined by the mathematical detection of Gaussian and Gamma distributions in partitioned but unselected patient data. For each trimester, red cell parameters were shown to be well described by Gaussian distributions. Platelet and white cell parameters were best described by Gamma distributions with the exception of eosinophil and basophil counts for which neither distribution was applicable. The reference ranges derived for each trimester are compared. PMID- 8472502 TI - Clostridium perfringens in the immunocomprised. PMID- 8472503 TI - Automated differential count rejections and in vitro platelet aggregation in blood from patients taking warfarin. PMID- 8472504 TI - Red cell distribution width (RDW) in sickle cell disease. PMID- 8472505 TI - Circadian variations in platelet aggregability in non insulin dependent diabetes patients (NIDDM). AB - Circadian rhythms of platelet activity have been extensively investigated in recent years in view of a possible correlation with the increased morning frequency of thrombotic events. Since a role of enhanced platelet activity has been suggested in diabetic macro- and microvascular disease, the aim of the present study was to analyze the circadian variations of in vitro platelet aggregability in patients with non insulin-dependent diabetes mellitus. Eighteen in-patients, ranging in age from 49 to 73 years, all in good metabolic control, were included in the study. Aggregometric patterns were analyzed in blood samples collected at 0700, 0900, 1100 and 1700. A significant increase of the threshold concentrations for ADP-collagen- and arachidonic acid-induced platelet aggregation has been observed in the interval 0700-1100 or 0700-1700, suggesting, also in diabetic patients as in normal subjects, a maximum of platelet activity in the morning, regardless of postural changes and timing of meals. PMID- 8472506 TI - [Heparinization in dialysis: new clinico-therapeutic directions]. AB - The authors describe side-effects of heparin administration during chronic dialytic treatment. For every complication they present a new clinical and therapeutic guideline. They then illustrate their method for monitoring heparin therapy with partial activated thromboplastin time and low dose heparin combined with prostacyclin. PMID- 8472507 TI - [The prevalence of arrhythmias in subjects over 80 years old. The prognostic role of anamnestic symptomatology and the therapeutic directions]. AB - 24-hour Holter monitoring was performed in 129 unselected subjects older than 80 years (69 women and 60 men) in order to evaluate arrhythmia incidence and to establish significance of symptoms; 56% patients had lipothymia and/or syncope, chest pain and palpitations, 44% were asymptomatic. All patients showed high incidence of hyperkinetic and hypokinetic arrhythmias; no significant differences between symptomatic and asymptomatic patients in arrhythmia incidence were seen. Moreover, no correlation could be seen of the symptoms reported by the patient to the incidence of any particular type of arrhythmia. In conclusion, these preliminary data suggest a criticism of the opportunity of indiscriminate and long term antiarrhythmic therapy. Nevertheless, Holter monitoring is useful in detecting hypokinetic arrhythmias of asymptomatic patients in whom pacemaker implantation is essential and curative. PMID- 8472508 TI - [The role of disease-modifying antirheumatic drugs (DMARDs) in the therapy of rheumatoid arthritis]. AB - The destructive process seen on the cartilage and on the sub-chondral bone of patients with rheumatoid arthritis, which is a chronic inflammatory disease of unknown aetiology, is in part unavoidable. The aim of the treatment is not only to reduce articular inflammation and/or to relieve pain, but also to prevent or delay articular damage and to improve quality of life of rheumatoid patients. The use of new available drugs, with a modern therapeutic approach, seems to be apt to improve considerably the outcome in rheumatoid patients. PMID- 8472509 TI - [An increase in the median plasma values of progesterone in luteal deficiencies treated with clomifene citrate in the early follicular phase]. AB - A clinical study performed during 265 cycles in 63 normo-ovulating and normo menstruating patients, of whom 27 with a luteal phase defect (LPD), assessed by morphological, hormonal, echographic and clinic criteria. These were given Clomiphene Citrate, 100 mg per day from the second to sixth day of the cycle, for a total of 108 cycles. The other 36 patients, without any luteal abnormality, were utilized as a control group during 156 cycles. At the end of the study there were no significant differences in hormonal, echographic and morphological parameters between the two groups. PMID- 8472510 TI - [Ocular involvement in rheumatoid arthritis]. AB - The authors evaluated ocular involvement in 23 patients affected by rheumatoid arthritis (RA) according to ARA criteria. Slit-lamp biomicroscopic examination showed signs of keratoconjunctivitis sicca in one patient (4%), while a positive bilateral Schirmer test was found in six subjects (26%). Fluorescein angiography, carried out in 11 of the 23 RA patients, showed retinal vasculitis in 18% of the patients examined, even if no clinical and ophthalmoscopic signs of retinal vessel inflammation were present. The authors suggest that fluorescein angiography should be performed in patients affected by particularly active RA, with recent onset of the disease (< 12 months), high titres of classical IgM rheumatoid factor and raised concentrations of circulating immune complexes. The study confirmed moreover the uncommon ocular toxicity related to the drugs frequently employed in RA treatment (antimalarials, gold salts, glucocorticoids). Indeed, only one case (4%) of posterior subcapsular cataract clearly related to steroid therapy was found. PMID- 8472511 TI - [The use of picotamide in nephropathy with mesangial IgA deposits. The effect on thromboxane generation]. AB - IgA nephropathy (Berger's disease) is one of the commonest forms of glomerular disease, not rarely progressing to renal failure. Hemostatic system activation may play a role in the development of glomerular injury. In a series of 12 adult patients affected with IgA nephropathy we have observed increased plasma levels of D-dimer, a stable end-product of cross-linked fibrin degradation that is considered a reliable index of blood clotting activation, as well as "in vitro" raised generation of thromboxane, the main platelet product of arachidonic acid metabolism that seems to play an important role in glomerulosclerosis. Picotamide, a novel antiplatelet drug acting as thromboxane synthase inhibitor as well as thromboxane receptor antagonist, administered for 8-12 weeks, was effective in reducing thromboxane generation. We conclude that picotamide may be useful in the management of glomerular nephropathy. PMID- 8472512 TI - [The role of infective intestinal complications on the course of Crohn's disease and ulcerative rectocolitis]. AB - The authors studied the incidence of protozoal and bacterial infection in 41 cases of Crohn disease und ulcerative colitis; the effect of anti infective therapy on the clinical course has also been tested. Patients with ulcerative colitis are more frequently involved in this type of complication than those with Crohn disease. Therapy has a positive influence on the course of the disease; therefore systematic study of the faeces for bacteria and parasites is necessary for a correct understanding of chronic inflammatory bowel disease and for specific treatment. PMID- 8472513 TI - [The use of contact lenses: the reality and outlook]. PMID- 8472514 TI - [Acute hepatitis, chronic hepatitis, cirrhosis: the intermediate and final stages in liver damage induced by chronic alcohol abuse]. AB - Having briefly analyzed the metabolism of ethanol in man, the author describes hepatocellular damage induced by alcohol abuse and histological, clinical and biohumoral features of acute alcoholic hepatitis, chronic hepatitis and cirrhosis. Seventy-five clinical cases of acute alcoholic hepatitis, chronic hepatitis and cirrhosis are also illustrated, studied and observed during five years. PMID- 8472515 TI - [Appropriate consumer behaviors: breakfast]. PMID- 8472516 TI - [A bioequivalence study of tablet and powder formulations of the nonsteroidal anti-inflammatory drug 2-methoxyphenyl 1-methyl-5-(p-methylbenzoylpyrrol)-2 acetamidoacetate]. AB - The purpose of the current study was that of evaluating and comparing the pharmacokinetic parameters (Tmax, Cmax, Ke, AUC, t1/2 beta) at the compounds TGA, tolmetin and MCPA obtained from healthy volunteers following a single oral administration of 600 mg of 2-methoxyphenyl 1-methyl 5 p-methylbenzoylpyrrole 2acetamide acetate (ST-679, previously called MED-15) in the form of tablets and envelopes in order to establish the bioequivalence of the above-mentioned preparations. The results obtained indicate that the administration of 600 mg of 2 methoxyphenyl 1-methyl 5 p-methylbenzoylpyrrole-2acetamide acetate (ST-679) tablets produces from a pharmacokinetics point of view, in man, pharmacokinetic parameters comparable to those obtained following administration of the same dose of the drug in envelopes. It is, therefore, possible to affirm that the preparation of 2-methoxyphenyl 1-methyl 5-p-methylbenzoylpyrrole-2acetamide acetate (ST-679) in envelopes is bioequivalent to that of the tablets. PMID- 8472517 TI - [A clinical study to determine the optimal dosage of ST-679 in the treatment of rheumatic diseases]. AB - A study was performed with 60 patients, affected by acute phase rheumatological pathology, in order to determine the optimum posology of ST-679 administered orally. The 60 patients were divided into 4 groups: 3 treated with ST-679 at different dosages (group 1 = 600 mg/die; group 2 = 1200 mg/die; group 3 = 1800 mg/die) and one with placebo (group 4 = 600 mg/die). The highest dosage employed (1800 mg/die) performs an excellent therapeutical activity which is equivalent to that at the 1200 mg in reducing pain symptomatology, but on the average less tolerated. The 600 mg dosage was less efficacious with respect to the two higher doses. PMID- 8472518 TI - [An evaluation of the therapeutic activity and tolerance of ST-679 in patients with osteoarthritis at different sites. A controlled double-blind study vs tolmetin]. AB - A multicentered study was carried out, under double-blind conditions, on 160 elderly patients afflicted with differently localized symptomatic osteoarthritis, for the purpose of evaluating the therapeutical efficacy and tolerability of ST 679 (per-os at a dose of 1200 mg pro die in 80 patients) and to compare them with those of tolmetin (per os at a dose of 1200 mg pro die in 80 patients). It was demonstrated that ST-679 was significantly active on all of the clinical parameters of the illness already recorded after a month of treatment. ST-679 was always excellently tolerated as shown by the scarce incidence of adverse reactions. Results of laboratory tests, of tests for hidden blood in the feces and of a gastroduodenoscopy confirmed the excellent biological and gastric tolerability of ST-679. ST-679 demonstrated, moreover, a significantly better tolerability with respect to tolmetin. PMID- 8472519 TI - [A bioequivalence study in man of tablet and capsule formulations of the nonsteroidal anti-inflammatory compound 2-methoxyphenyl 1-methyl-5-(p methylbenzoylpyrrol)-2-acetamidoacetate]. AB - ST-679.(2-methoxyphenyl 1-methyl-5p-methylbenzoyl pyrrole-2-acetamide acetate) is a novel non-steroid anti-inflammatory agent consisting of tolmetin linked by an amide link to guaiacole-esterified glycine. The above reported study was aimed at to evaluation and comparison of pharmacokinetic parameters (Tmax, Cmax, AUC, t1/2 beta) of TGA, tolmetin, and MCPA in healthy volunteers after a single oral 600 mg tablet or capsule of ST-679 in order to assess the bioequivalence of the two formulations. The findings obtained show that pharmacokinetic parameters after administration of a 600 mg tablet are comparable to those after a 600 mg capsule. The two formulations may therefore be considered bioequivalent. PMID- 8472520 TI - [The drug treatment of postoperative pain]. AB - The study, conducted on 40 patients with pain resulting from "minor" general surgery, for the purpose of evaluating the efficacy and tolerability of ST-679 (administered in a single oral dose of 1200 mg in 20 patients) and to compare them with those of paracetamol (administered in a single oral dose of 1000 mg in 20 patients), demonstrated that the new drug was active on all recorded parameters and superior to the reference drug. The evaluation of the evolution of pain, performed using the Scott-Huskisson visual analog scale, evidenced that the maximum analgesic efficacy of ST-679 is reached after 1 hour and 15 minutes from assumption and remains unaltered until the final observation (6 hours). The paracetamol registers maximum analgesic efficacy after 30 minutes, but does not remain constant for the entire observation period. All the other parameters evaluated (variation in pain intensity, peak of analgesic activity and total remission of pain) are significantly favorable to ST-679. The tolerability of ST 679 was very good and better than the reference drug. PMID- 8472521 TI - [The treatment of postoperative pain in obstetrical-gynecologic surgery. A comparative study between ST-679 and paracetamol]. AB - In double-blind conditions, ST-679 (a single oral 1200 mg dose in 20 patients), or paracetamol (a single oral dose of 1000 mg in 20 patients) was administered to forty patients who presented pain as a result of obstetrical-gynecological surgery. The study proposed to evaluate the analgesic efficacy and tolerability of ST-679, a new non-steroid antiphlogistic drug, as compared to a reference drug amply utilized in clinical practice such as paracetamol. The average estimation of tolerability, with regard to paracetamol, was significantly in favor of ST 679. PMID- 8472523 TI - [A comparative evaluation of the remission from acute lumbar-sciatic pain following treatment with meclofenamic acid and naproxen]. AB - This study was performed to assess the analgesic effect and the onset of action of meclofenamic acid compared with naproxene in patients affected by acute lumbar sciatic pain. Thirty patients of both sexes were randomly allocated to 2 groups of 15 patients each; the first group was treated with meclofenamic acid (200 mg b.i.d.) and the second with naproxene (500 mg b.i.d.). Both drugs were administered as suppositories for a week. The intensity of pain, both at rest and after movement, was assessed by means of analogic scales at basal time and 15, 30, 60, 180, 360 minutes, 4 and 8 days after the first administration. Both types of pain were significantly decreased with respect to basal values in meclofenamic acid group (P < 0.01), 60 minutes after onset of treatment, while in the naproxene group the effect was later. Moreover the analgesic effect was significantly greater in the meclofenamic acid group with respect to the naproxene group, after 15 minutes for pain at rest (P < 0.05) and after 30 minutes for pain after movement (P < 0.02). Similarly, after 4 and 8 days, both types of pain improved to a larger extent in the meclofenamic acid group with respect to the naproxene group (P < 0.05 after four days and P < 0.01 after eight days). This study has shown that meclofenamic acid has greater efficacy and faster analgesic effect than naproxene. Meclofenamic acid has proved to be a drug of choice in the treatment of slight to moderate musculo-skeletal pain syndromes. PMID- 8472522 TI - [An evaluation of the analgesic activity and tolerance of ST-679 in patients with pain following orthopedic and traumatological interventions]. AB - The analgesic efficacy and tolerability of ST-679 (administered in a single oral dose of 1200 mg) was evaluated in a double-blind parallel-group study, as compared with paracetamol (administered in a single oral dose of 1000 mg) on 40 patients with pain following orthopedic or traumatological surgery. ST-679 was shown to possess better analgesic qualities with respect to paracetamol, in that the effect establishes itself more quickly and, moreover, both the maximum analgesic activity performed as well as the constant level on which such activity tends to stabilize is greater. No adverse reaction was recorded for either treatment, but ST-679 demonstrated a better tolerability with regard to paracetamol. PMID- 8472524 TI - [The behavior of the fibrinogen polymerization curve in hypercholesterolemic subjects]. AB - Several epidemiological and clinical studies performed in subjects with risk factors for atherosclerotic cardiovascular events, have shown changes in plasma levels and/or activities of coagulation factors that could suggest a prothrombotic state. We studied the behaviour of the fibrinogen polymerization curve (FPC), a spectrophotometric technique evaluating the kinetics of fibrinogen transformation into fibrin, in 68 subjects with and without hypercholesterolemia. Significant differences were found between FPCs of subjects with serum cholesterol > 240 mg/dl and < or = 240 mg/dl respectively. In fact, FPCs of the first group showed high reaction velocity rate, short latency time and higher optical density rate, final readings; besides, the behaviour of FPCs was not correlated to plasma fibrinogen concentrations. Therefore, FPC could be a useful test to identify a thrombophilic condition in hypercholesterolemic patients. PMID- 8472525 TI - [Nimodipine in ischemic cerebropathy]. AB - Fifty patients of either sex with acute and chronic cerebrovascular disorders were submitted to an observation protocol and treated with oral nimodipine (tablets or drops) at a daily dosage of 90 mg for 1 to 3 months. Nimodipine proved useful both from the therapeutic point of view and for its easy handling in acute pathology (TIA, RIND, minor stroke, complete stroke) as well as chronic cerebral ischemia. The drug was well tolerated both locally and systemically; in patients with concomitant arterial hypertension, nimodipine reduced blood pressure with a tendency towards stabilization at near-normal levels. PMID- 8472526 TI - [A new granular effervescent 10-mg formulation of cisapride in the treatment of gastroesophageal reflux]. AB - The efficacy and tolerability of Cisapride effervescent granules for treatment of gastroesophageal reflux disease were compared to a metoclopramide-dimeticone combination. The double-blind study was performed in two groups of 10 patients each who received 3 sachets daily of either drug for 8 weeks. Cisapride effervescent granules induced a statistically significant improvement of 75% of symptoms (6/8) while this improvement was obtained with the reference drug for only 60% (3/5). Statistical evaluation showed Cisapride effervescent granules to be more effective than the reference drug for 2 of 5 evaluable symptoms; mean global improvement amounted to 83 vs 58%. Final physician opinion was more favorable to Cisapride effervescent granules than to the reference drug (p < 0.005). Treatment did not have to be withdrawn nor were clinically significant changes of laboratory values observed. Both drugs were found to be well tolerated without differences between the two groups. Three patients treated with Cisapride effervescent granules complained of short-lasting mild abdominal discomfort the relations of which to the drug was doubtful, and which subsided spontaneously without need to withdraw treatment or to apply other types of therapy. PMID- 8472527 TI - [The utility of a classification scale of lumbar pain for the diagnosis of the fibromyalgia syndrome]. AB - To help fibromyalgia syndrome's diagnosis, the authors propose the use of Back Pain Classification Scale (BPCS), verbal test for pain analysis, able to distinguish between organic and functional disease. Two-hundred patients suspected for fibromyalgia and forty controls completed the questionnaire and so it was possible correctly to distinguish patients with organic disease from those affected by fibromyalgia. The authors conclude that BPCS can represent a useful tool for fibromyalgia diagnosis. PMID- 8472528 TI - [An open study on the clinical efficacy of citicoline in patients with chronic cerebral vasculopathy]. AB - In this study we evaluated the safety/efficacy of citicoline in 30 patients affected by atherosclerotic processes with cerebral localization. Aim of this study was to confirm, from a clinical point of view, the efficacy of citicoline in increasing blood flow in the vascular zone and in exerting a trophic action on cerebral cells improving the symptoms related to the chronic cerebrovasculopathy. Therapeutic effect was evaluated, by means of subjective parameters, at the beginning, during and at the end of the study. The results obtained was statistically analyzed confirming the efficacy of citicoline on the subjective symptomatology. Safety was excellent in all cases. PMID- 8472529 TI - [Gamma-vinyl-GABA: the first trials in Italy]. AB - Vigabatrin (gamma-vinyl-GABA), a structural analogue of GABA, is a selective inhibitor of GABA transaminase. Vigabatrin has been effective in patients with refractory epilepsy. We treated patients with complex partial seizures and some of them also with secondary generalized seizures. Vigabatrin was administered as "add on therapy" (Table 1) and monotherapy (Table 2). As to table 1, concerning a variety of treatments and too few patients we could not reach any definitive statistical conclusion (paired Student's t test not significant). In table 2 the paired Student's t test was significant with p < 0.01. Longer follow-up is needed to determine whether the clinical effect is maintained and no severe side effects appear. PMID- 8472530 TI - [The therapy of Raynaud's phenomenon]. AB - Management of Raynaud's phenomenon is essentially "symptomatic". Some hygienic behavioral rules intended to eliminate all factors (cold, cigarette smoking, drugs, traumata) apt to trigger the phenomenon are essential. A number of drugs have been suggested for treatment: Nifedipine had been found to be effective in reducing frequency and duration of vasospastic attacks thanks to its mainly vasodilatory action, to its ability to influence platelet activity as well as to its antithrombotic effect. Also the most recent generation of calcium-channel blockers (nicardipine felodipine, isradipine, etc.) were found to have therapeutic efficacy comparable to that of nifedipine, with the added advantage of a once daily dosage. Ketanserin, a serotoninergic antagonist, is a valid alternative to calcium-channel blockers for treatment of Raynaud's phenomenon in as much as it can reduce frequency, duration and severity of vasospastic attacks, although not all authors agree upon this point. The use of prostanoids is usually reserved for cases of Raynaud's phenomenon associated with systemic sclerosis accompanied by extensive trophic disorders. Surgery is indicated only in selected cases. PMID- 8472531 TI - [Scrofula in an elderly woman. A clinical case]. AB - The case is described of an elderly woman with scrofula. The peculiarity of this case consisted in the comparative rarity of primary tubercular lymphadenopathy (a pathology that in the past used to be common in poor socioeconomic conditions) even considering the present renewed diffusion of tuberculosis; especially as this elderly patient had no previous history of tubercular infection. PMID- 8472532 TI - The chicken histone gene family. AB - 1. Most of the chicken 43 core and H1 histone genes belong to two major histone gene clusters. 2. Each of six H1 genes encodes a different H1 protein sequence. 3. The known core histone genes, four H2A, seven H2B, and seven H3 genes, respectively, encode two, three and three different protein variants, whereas the four known H4 genes encode the same amino acid sequence. 4. The core histone genes have particular transcription regulatory elements within the 5'-flanking regions and the regulations of their expressions are distinct, even though they are members of the same core histone gene family. 5. There are some undefined differences in the DNA structures of the particular core histone genes in various chicken tissues and these structural variations probably result in differences in their transcriptional regulation. PMID- 8472533 TI - Expression of the myc proto-oncogene in the rainbow trout Oncorhynchus mykiss. AB - 1. The myc proto-oncogene is shown to be expressed in the pituitary gland, brain and heart of the rainbow trout. 2. Based on transcript sizes the pituitary gland expressed B-myc and L-myc, the brain expresses L-myc and the heart expresses either C-myc or L-myc. 3. Pituitary B-myc is expressed at a level 3-fold greater than liver C-myc and 8-fold greater than the heart transcript. 4. The amounts of the pituitary B-myc and heart transcript nearly double as the fish approach sexual maturity. PMID- 8472534 TI - Ecdysteroids during development in the ovine parasitic nematode, Haemonchus contortus. AB - 1. Samples of embryonating eggs, infective larvae, fourth-stage larvae, young adults, and male and female mature adults of Haemonchus contortus were collected for steroids analysis; lipids were extracted, partially purified, fractionated with HPLC, and analyzed for ecdysteroids by radioimmunoassay. 2. Free ecdysone and 20-hydroxyecdysone were detected in all samples; maximal concentrations occurred in the fourth-stage larvae and young adults. 3. Conjugated ecdysone and 20-hydroxyecdysone were detected in all samples but the infected larvae; maximal concentrations occurred in the fourth-stage larvae and young adults. 4. Patterns of ecdysteroid occurrence support regulatory roles in embryogenesis, cuticular deposition, and gonadogenesis. 5. Relative concentrations of ecdysteroids are comparable to those previously reported in eggs and adults of Ascaris suum. PMID- 8472535 TI - Chicken eggshell porphyrins and the glyoxalase pathway: its possible physiological role. AB - 1. The plasma 4,5-dioxovaleric acid (DOVA) levels of two different breeds of chicken were determined and found to be higher in the group with a higher porphyrin eggshell content. 2. The erythrocyte and uterus glyoxalase II activity, investigated by means of a new spectrophotometric method, was found to be significantly higher in the group with a low porphyrin eggshell content. 3. A comparative genetic study of two chicken populations, one with white and one with dark eggshells, showed different gene frequencies for the glyoxalase I polymorphism. 4. An interpretation of these data suggests that the glyoxalase pathway may be involved in the metabolism of early porphyrin precursors. PMID- 8472536 TI - Comparison of hemocyte components from Schistosoma mansoni (Trematoda) susceptible and resistant Biomphalaria glabrata (Gastropoda) that cross-react with larval schistosome surface proteins. AB - 1. Cross-reactive antigens between larval Schistosoma mansoni and hemocytes from schistosome-resistant and susceptible strains of Biomphalaria glabrata were identified and compared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting and surface radioiodination. 2. Four sporocyst (larval S. mansoni) surface antigens (27, 39, 40 and 70 kDa) reacted with antibodies to hemocytes from resistant snails whereas only one surface antigen (70 kDa) was recognized by antibodies to hemocytes from susceptible B. glabrata. 3. The wider distribution and greater frequency of cross-reactive antigens between resistant hemocytes and sporocysts suggests that such cross reactivity may be involved in the hemocyte-mediated killing of larval schistosomes that occurs in this host-parasite system. PMID- 8472537 TI - Quantification, immunoaffinity purification and sequence analysis of a pigment dispersing hormone of the shore crab, Carcinus maenas (L.). AB - 1. A sensitive sandwich-ELISA for pigment-dispersing hormone (PDH) with a detection limit of approximately 5 fmol per well has been developed using primary IgG and secondary biotinylated IgG fractions from an antiserum against beta-PDH and streptavidin-peroxidase conjugate for detection. 2. ELISA determinations in different parts of the central nervous system of the shore crab Carcinus maenas revealed maximum levels of 15.1 pmol immunoreactive PDH in the two eyestalk ganglia of one crab, 3.6 pmol in the sinus glands, 2.8 pmol in the brain and 0.8 pmol in the thoracic ganglia. 3. Carcinus PDH was purified from whole eyestalk ganglia and sinus glands by use of a simple two-step purification procedure consisting of immunoaffinity-prepurification on an anti-PDH IgG-protein A Sepharose column and HPLC. 4. Automated gas-phase sequencing of the purified peptide and FAB-mass spectroscopy unambiguously revealed the sequence of Carcinus PDH as NSELINSILGLPKVMNDAamide (M(r) 1927.2 Da), which is identical to the beta PDH of other brachyuran crustaceans. PMID- 8472538 TI - In vitro poly-(ADP-ribosyl)ation of chromatin proteins in the rat tapeworm, Hymenolepis diminuta. AB - 1. (ADP-ribose)-transferase activity in crude chromatin of H. diminuta was demonstrated. 2. Chromatin proteins were ADP-ribosylated in vitro and selectively extracted. 60, 12 and 18% of the (ADP-ribose)n of chromatin proteins was associated with total histones, histone H1 and histone H2B, respectively. 3. The extent of oligo-(ADP-ribose) compared to total (ADP-ribose)n in the chromatin fraction, in the histone fraction, the histone H1 fraction and the histone H2B fraction was 45, 60, 26 and 49%, with an average chain length of 2.8, 2.1, 1.8 and 2.6, respectively. 4. Analysis of (ADP-ribosyl)n-ated proteins by acetic acid/urea polyacrylamide gel electrophoresis demonstrated that histone H1, histone H2B and a 35 kDa non-histone protein were major (ADP-ribose)n acceptors. PMID- 8472539 TI - Ascorbate-2-sulfate sulfohydrolase in fish and mammal. Comparative characterization and possible involvement in ascorbate metabolism. AB - 1. The new assay conditions were determined for crude and purified enzyme ascorbate-2-sulfate sulfohydrolase from liver tissues of two fish species and bovine. 2. The major departure from the existing indirect method, based on reduction of 2,6-dichlorophenolindophenol (DCIP) by released ascorbic acid and change from pink-blue to a colorless molecule, takes into account the shift of maximum absorbance of DCIP from 516 nm at pH 5.14 to 600 nm at pH 6.5. 3. The direct method is based on colorimetric assay of liberated ascorbic acid including correction for interfering substances. The optimum pH for both fish ascorbate sulfatases was 5.5. 4. The Km for bovine ascorbate sulfatase was confirmed to be approximately 7 mM at 37 degrees C. 5. Partly purified ascorbate-sulfate sulfohydrolase has a Km value in rainbow trout of 0.4 mM and it changes very little in the range of water temperatures characteristic for this stenothermic fish species. 6. In eurythermic chub, the Km values increased from 1.2 to 4.3 mM with rising temperatures. PMID- 8472540 TI - Mitogenicity of the earthworm's (Eisenia foetida) insulin-like proteins. AB - 1. Biologically active glycolipoprotein complex (G-90), isolated from whole earthworm tissue extract (Eisenia foetida), was separated into seven fractions by gel-filtration. 2. It has been shown by radioimmunoassay that each of the fractions, except the lightest one, is cross-reactive with porcine anti-insulin antibodies. Molecules that possess such activity were detected by immunoblotting. 3. All fractions, except the heaviest and the lightest one, stimulate mammalian normal and transformed cell proliferation in serum-free conditions in vitro. The intensity of stimulation depends on cell type. Stimulation is completely abolished if the medium is supplemented with fetal calf serum. PMID- 8472541 TI - Gender dependence of D-aspartate oxidase activity in rat tissues. AB - 1. A gender difference in D-aspartate oxidase activity was demonstrated for the first time in rat tissues. 2. In adult Wistar rats, the hepatic enzyme activity was constantly higher in females than males. The renal activity showed a similar tendency. 3. The gender difference in the hepatic activity was not observed in newborn animals, but became apparent with growth almost in parallel with sexual maturation. 4. The hepatic activity in females was greatly affected by pregnancy and parturition. PMID- 8472542 TI - A comparative study of DNA amount and nuclear dry weight in four different species (Rana catesbeiana, Salmo gairdneri, Gallus domesticus and Homo sapiens). AB - 1. Quantitative electron microscopic and cytophotometric determinations of average nuclear weight, unit weight of chromatin fiber, chromatin fiber diameter and DNA amount were made and compared from lymphocytes in human, chicken, frog and trout. 2. From these determinations the "packing ratio" of DNA in chromatin fibers was calculated. 3. Nuclear mass and DNA amounts were highest in frog and lowest in chicken, while fiber diameter and mass of unit fiber measured highest in trout followed by chicken, frog and man. 4. The packing ratios were 21.4 in chicken, 35.2 in human, 47.0 in trout, 51.1 in frog and show a trend of being lower in amniotes than in anamniotes. 5. As only four species were studied, no conclusions regarding evolutionary implications or relationships between them could be made from these measurements. PMID- 8472543 TI - The isolation and properties of whole casein: some implications for comparative studies. AB - 1. Problems in the isolation of whole casein from bovine milk are considered. A summary is given of our experiences in its isolation. 2. The physical characteristics, sedimentation velocity, heterogeneity, absorptivity, nitrogen, phosphorus and carbohydrate contents of whole casein prepared from normal and sub clinical mastitic milk samples by a variety of methods are compared. The methods are acid precipitation, high-speed centrifugation, with and without added calcium (II), and ammonium sulphate precipitation. 3. A description is given of the low temperature ammonium sulphate procedure preferred for the isolation of whole casein, especially when it is to be used for subsequent fractionation for conformation and micelle studies. 4. The question of the use of bovine casein as a paradigm for the caseins of other mammalian species and the need for further studies of the physical, chemical and biological properties of the caseins are discussed. PMID- 8472544 TI - Prolactin binding sites in the adrenal glands of mink (Mustela vison). AB - 1. The purpose of this study was to determine if the mink adrenal gland might be a target organ for prolactin by establishing whether or not binding sites for the hormone exist in adrenal cell membranes. 2. Adrenal glands were collected from adult female mink in November, 1991, homogenized and subjected to differential centrifugation into three particulate fractions; 1500, 15,000 and 50,000 g. All binding determinations were made using 125I-oPRL and 200-300 micrograms protein from the 50,000 g particulate fraction. Optimal binding occurred within 8 hr at 25 degrees C. 3. Scatchard analysis of saturation data revealed a single set of high affinity (Kd = 9.27 x 10(-11) +/- 1.63 M), low capacity (Bmax = 34.22 +/- 5.37 fmol/mg) binding sites. 4. Binding sites appeared to be hormone specific as only oPRL (73% displacement) and oLH (8% displacement) inhibited binding of 125I oPRL to adrenal membranes. No inhibition of 125I-oPRL binding to adrenal membranes occurred in the presence of a 500-fold excess of bTSH, oGH or oFSH. 5. Prolactin binding sites were readily detected in adrenal and kidney tissue, but were low in liver and almost non-detectable in spleen or lung tissue. 6. Our data suggest that the mink adrenal gland is a target organ for prolactin and that an interaction between the pituitary and adrenal glands may exist that is important for the regulation of such physiological processes as fur growth cycles. PMID- 8472545 TI - Development of an HPLC method to estimate hexosamines and its application to determine mucin content in rat and human gastric mucosa. AB - 1. An HPLC analysis of hexosamines and related compounds modified from the Waters Pico-Tag amino acid analysis procedure is described. 2. This method is applicable to determine glucosamine and galactosamine not only in the hydrolyzate of purified glycoconjugate such as gastric mucin and ovalbumin but also in crude materials such as rat gastric mucosal extract and powdered bovine nasal cartilage. 3. Compared with a conventional colorimetric hexosamine determination, sensitivity of this method is almost 100 times higher. 4. By applying this method, a simple but highly sensitive procedure to determine mucin content in a crude stomach specimen of rat and that in a biopsied human gastric mucosa was also developed. PMID- 8472546 TI - Molecular cloning and expression of yellowfin porgy (Acanthopagrus latus houttuyn) growth hormone cDNA. AB - 1. The growth hormone cDNA of yellowfin porgy (ypGH cDNA) consisted of 915 base pairs. 2. The deduced amino acid (aa) sequence showed that the pre-GH comprised 204 residues, of which the first 17 residues formed a signal peptide. 3. Comparison of aa sequence of ypGH to seabream, tuna, rainbow trout and chum salmon showed that ypGH shared 95.1, 94.1, 65.3 and 62.4% homology with these species, respectively. 4. By expressing the ypGH cDNA in E. coli, a polypeptide around 23 kilodaltons (kDa) was found which was immunoreactive to GH antibody. PMID- 8472547 TI - Expression of the albumin gene in the yolk sac and liver during chick embryogenesis. AB - 1. Albumin mRNA is first detectable in vascular yolk sac on the third day of egg incubation, increases to peak level on day 14 and declines to zero by day 19. 2. Vascular yolk sac RNA contains a 6-10-fold higher level of albumin transcripts compared to non-vascularized yolk sac, suggesting a role for vascularization in promoting albumin gene expression. 3. Embryonic liver albumin transcripts are first detectable at day 6.5, increase 6-fold by day 8, continue to rise at a lower rate until day 14 and remain constant thereafter. 4. Albumin protein synthesis in liver cubes also exhibits a large increase over days 7-10. In contrast, another liver-specific constitutive protein, apolipoprotein B, shows a different biosynthetic pattern. 5. The data suggest development of hepatic albumin gene-specific regulatory factors over days 7-10. PMID- 8472548 TI - Cerebral specialization for speech perception and movement organization in adults with Down's syndrome. AB - Adults with Down's syndrome and a group of undifferentiated mentally handicapped persons were examined using a free recall dichotic listening procedure to determine a laterality index for the perception of speech sounds. Subjects also performed both the visual and verbal portions of a standard apraxia battery. As in previous research, subjects with Down's syndrome tended to display a left ear advantage on the dichotic listening test. As well, they performed better on the apraxia battery when movements were cued visually rather than verbally. This verbal-motor disadvantage increased as the left ear dichotic listening advantage became more pronounced. It is argued that the verbal-motor difficulties experienced by persons with Down's syndrome stem from a dissociation of the functional systems responsible for speech perception and movement organization (Elliott and Weeks, 1990). PMID- 8472549 TI - Handedness, sex, and familial sinistrality effects on spatial tasks. AB - Left-handed (N = 109) and right-handed (N = 115) undergraduates (99 males, 125 females) received the SIBT (a "mental rotation" test), the 3DD (3-dimensional drawing test), and a family sinistrality (FS) questionnaire. Left-handers were further separated into consistent left-handed (CLH) and inconsistent left-handed (ILH) subgroups, based on consistency of hand preference. On the spatial tests, males outperformed females, with no overall handedness effects. Also, for males, CLH's (but not ILH's) performed significantly worse than right-handers on the SIBT, but this difference was not found on the 3DD. For females, no handedness subgroup differences were found on either spatial tasks. Familial sinistrality was twice as common in left-handers as in right-handers. Among males, the incidence of FS+ in the CLH subgroup also was over twice that for ILH's. Thus, where left-handers report a greater incidence of FS+, and are inferior to right handers in mental rotation skill, it is CLH's (particularly males) who contribute mostly to these effects. The results suggest that previous discrepant findings reported in studies of the cognitive correlates of left-handedness may be due in part to the mixing of two distinct left-handed subgroups. An understanding of the differences between them may be crucial for better understanding the genetic and neurobiological mechanisms underlying handedness. PMID- 8472550 TI - Analysis of the syndrome of unilateral neglect. AB - Using a variety of clinical measures of unilateral neglect 40 right hemisphere lesioned stroke subjects were compared in terms of neuropsychological deficit. The results of the study encourage the view that unilateral neglect is a complex syndrome and subjects who indicate the disorder may vary in systematic dimensions. There are at least two factors contributing to the neglect syndrome- a scanning factor of external stimuli and a disrupted internal representation of space factor. Both the obtained factors were correlated with functional independence at 6 months post-stroke in a further group of 27 right hemisphere lesioned stroke patients. It is probable that most commonly these factors co exist and form the classical neglect syndrome but theoretically they may occur separately and this leads to implications for management. PMID- 8472551 TI - Visuospatial judgment: a cross-national comparison. AB - Two samples of American and Italian 8 to 12 year-old children were compared for their performance on the Judgment of Spatial Orientation Test. No group difference emerged and, consequently, the same normative standards for performance can be applied in both countries. In both groups males performed better than females. PMID- 8472552 TI - Laterality in cats: paw preference and performance in a visuomotor activity. AB - Laterality in paw use was investigated over a period of 6 years in 44 domestic cats trained to perform a reaching movement toward a moving spot of light. Both paw preference and paw performance were recorded. At a 50 percent criterion, no significant paw preference was found at the level of the group. When a 90 percent criterion was considered, 23 subjects had a significant preference for one paw. Among these strongly lateralized animals, there were more left- (N = 17) than right-pawed (N = 6) cats. The analysis of visuo-motor performances included reaction time, movement time, and reaching accuracy. Lateralized cats had a faster reaction time than nonlateralized cats. The more-used paw had a shorter reaction time, a shorter movement time, and was also more accurate than the less used paw. Thus, the findings demonstrate a functional advantage of being lateralized. Moreover, the results confirm the existence of an asymmetry of paw preference in cats and show a consistent relation between paw preference and performance. PMID- 8472553 TI - Spontaneous recovery of impaired memory span: does comprehension recover? AB - We have previously described a patient, T.B., who had a memory span of two digits and a sentence span of three words. He showed no evidence of effects of either phonological similarity or word length on span and his deficit was interpreted as reflecting the impaired functioning of the phonological loop component of working memory. Analysis of his language comprehension indicated normal processing of short sentences, together with a marked deficit in understanding long sentences, whether these were presented visually or auditorily (Baddeley and Wilson, 1988). When re-tested after several years, T.B.'s memory span had increased to nine digits, and showed clear effects of phonological similarity and word length. His performance on a series of language comprehension tests indicated a complete recovery, although he continued to show impairment on two tests of phonological awareness. These results are consistent with the proposed link between phonological working memory and language comprehension. In addition, they indicate a dissociation between short-term phonological memory and phonological awareness. PMID- 8472554 TI - A differential effect of concurrent verbal activity on right arm movements rightwards and leftwards. AB - Twenty right-handed male subjects had to follow a target which moved horizontally with a velocity of 40 degrees/s either rightwards or leftwards by moving their right arm. During the pursuit movement, subjects had to speak a sentence or to accomplish this procedure without speaking. It could be shown that while subjects spoke, the pursuit movement was performed more inaccurately than during the control session. Furthermore, it was shown that during concurrent speaking, pursuit movements rightwards were more inaccurate than movements to the left. This result is in line with theoretical implications according to which visually guided right-arm movements rightwards are controlled by a neural network located in the left hemisphere, whereas right-arm movements leftwards are controlled by a neural network distributed over both hemispheres. PMID- 8472555 TI - Homing in on neglect: a case study of visual search. AB - We report three studies of visual search in a patient with left neglect after a right parietal infarct. Manipulations whereby the patient's attention is explicitly drawn to the spatial extent of the page on which the stimuli for cancellation are displayed have little or no effect on the number of targets cancelled. The results are consistent with a "zoom lens" model of attentional deployment. "Neglect" on search tasks seems to reflect a systematic bias that emerges when global attention is constricted to permit analysis of local features. PMID- 8472556 TI - Unconscious processing in memory recall. A study of three amnesic patients. AB - The sudden resurgence of precise information some time after the failure of its recall (memory block) suggests the intervention of unconscious processes. In normal subjects the experimental demonstration of such processes meets with methodological snags. They are avoided in patients with a pure amnesic syndrome because retrograde amnesia produces many instances of missing memories, while anterograde amnesia prevents the patient from consciously thinking about it. Three patients with a pure amnesic syndrome were submitted to 4 interviews over 12 days on 3 topics concerning places and itineraries that were very familiar before the disease, and a shocking event of their life. Retrieved memories were compared to those of normal matched subjects. The results showed a dramatic increase for memories of places and itineraries over sessions, and the absence of improvement of autobiographical memories. These findings underline the role of the activation of unconscious processes in recall and the different status of semantic and episodic memory. PMID- 8472557 TI - Selective increase in the right hemisphere transcranial Doppler velocity during a spatial task. AB - Transcranial Doppler ultrasonography of the middle cerebral arteries was performed during two tasks: sorting of mah-jongg tiles and vibratory stimulation. These tasks selectively increase cerebral blood flow by positron emission tomography. The purpose of this study was to determine if analogous increases in cerebral blood flow velocity could be detected. We measured flow velocity during right hand manipulation followed by left hand manipulation, or vice versa, with resting studies in between. The average increase in the mean velocity, by paired t-test, was significant for the right middle cerebral artery with both left hand (p < .0005) and right hand (p < .005) tile sorting. For the left middle cerebral artery, there was an increase in the mean velocity with right hand (p < .005) but not for left hand sorting (p = .13). These findings support the importance of the right hemisphere in the performance of this type of spatial task. No significant flow velocity increase occurred during vibratory stimulation. PMID- 8472558 TI - Lexical-phonological processing of functors: evidence from fluent aphasia. AB - The purpose of this study was to investigate how functors are processed at the lexical-phonological level. Four fluent aphasics with impaired ability to fully activate entries in the phonological lexicon, as revealed by their noun production, were asked to repeat and read aloud individual functors. Similarities between their functor and noun production (e.g., level of performance, production of phonological errors) indicated that functors are stored along with content words in the phonological lexicon, and are stored with a similar abstract structure. We also considered whether the sentence-planning system can facilitate the phonological encoding of functors presented in isolation. PMID- 8472559 TI - Impaired discrimination of familiar from unfamiliar faces. AB - We report investigations of the face processing abilities of J.T., a man who had suffered a right hemisphere stroke. J.T. showed a marked problem in discriminating between familiar and unfamiliar faces, with no corresponding problem in discriminating familiar from unfamiliar names. The problem with faces was still found 2 years after the stroke, but had resolved at long-term follow-up (9 years post stroke). When given unlimited time to respond, J.T. did not show any problem in recognising familiar faces, but tended to think that he recognised unfamiliar faces. When under time pressure, however, J.T. also failed to recognise a number of familiar faces which he could readily identify when the time pressure was removed. J.T.'s ability to remember a face and to think of other people who might be similar in appearance was affected by whether or not the face seemed familiar or unfamiliar to him. Hence, whatever underlay the spurious sense of familiarity was sufficient to produce real differences between the way in which genuinely unfamiliar and spuriously familiar faces were seen, leading us to suggest that his impaired discrimination of unfamiliar from familiar faces reflected a malfunction of face recognition units. PMID- 8472560 TI - Phasic and tonic alertness in Alzheimer's disease. AB - Phasic alertness (the rapid mobilization of resources to process an expected stimulus) was examined in Alzheimer patients and normals by a choice RT task in which the stimulus was usually preceded by a warning signal. The time subjects needed to attain maximal phasic alertness was determined by varying the Stimulus Onset Asynchrony (SOA) between the warning and the stimulus. In comparison to trials without any warning, presentation of a warning signal reduced the RT of Alzheimer patients as much as it did that of normals. Similarly, the SOA necessary for maximal alertness was the same in Alzheimer patients and in normals. Maintenance of tonic alertness was investigated by examining how RT changed across a long period of continuous testing. Alzheimer patients and normals showed a similar rise in RT with increasing time on task. These results suggest that phasic and tonic alertness are relatively unimpaired by Alzheimer's disease. PMID- 8472561 TI - Recall and recognition memory in Parkinson's disease. AB - This study is concerned with recall and recognition memory in patients with Parkinson's disease. The results show that the Parkinson group was significantly impaired on tests of free recall compared to a group of age matched controls. By contrast, when given tests of recognition memory for the same items their performance was practically identical. In recall, significant main effects are reported for serial position and list presentation but no qualitative differences were observed between the two groups on these measures, both of which showed a primacy and recency effect. However, the control subjects recalled significantly more words in their original order of presentation than the patient group, a difference which appears to have occurred at the level of input. It was concluded that although the patient group was able to adopt and use similar strategies to the control subjects, they were less efficient in using these, a difficulty which was attributed to limited capacity due to mental slowness. PMID- 8472562 TI - Blood conservation in critical care--the evidence accumulates. PMID- 8472563 TI - Improved communication with the Passy-Muir valve: the aim of technology and the result of training. PMID- 8472564 TI - Pediatric intensive care unit, "know then thyself". PMID- 8472565 TI - Clinical performance of a blood gas monitor: a prospective, multicenter trial. AB - OBJECTIVE: To prospectively assess the clinical performance of a fluorescent optode-based blood gas monitoring system that is designed to perform arterial pH, PCO2, and PO2 measurements as frequently as clinically required without violating the integrity of the arterial catheter tubing system or permanently removing blood from the patient. DESIGN: A prospective, multicenter study to compare modern blood gas analyzer measurements with the coinciding measurements of the blood gas monitoring system. SETTING: Four intensive care units (ICUs) in academic centers with varying patient populations, blood gas measurement routines, and blood gas laboratory facilities. PATIENTS: Adult ICU patients (n = 117), with appropriately functioning radial arterial catheters in place, who were assessed as likely to require multiple arterial blood gas measurements for > or = 2 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 117 patients had 1,341 concurrent blood gas analyzer and monitor measurements of arterial pH, PCO2, and PO2 over a 1- to 4-day period. The range of values were 7.14 to 7.64 for arterial pH, 19 to 98 torr (2.5 to 13.0 kPa) for PaCO2, and 38 to 413 torr (5.1 to 54.9 kPa) for PaO2. Linear regression analysis of the optode based monitor compared with the electrode-based blood gas analyzer demonstrated r2 values of .85 for pH, .92 for PCO2, and .94 for PO2. Comparative statistical analyses for bias (mean difference between analyzer and monitor) and precision (standard deviation of the mean difference [+/- SD] between analyzer and monitor) were respectively:-0.004 and +/- 0.027 for pH; -0.8 torr (-0.11 kPa) and +/- 2.4 torr (0.32 kPa) for PCO2; -2.2 torr (-0.31 kPa) and +/- 8.7 torr (1.2 kPa) for PO2. CONCLUSIONS: Clinical performance of this fluorescent, optode-based blood gas monitoring system demonstrates stability, consistency, and accuracy comparable to modern blood gas analyzers. This system withstood the normal abuse and rigors of clinical conditions common to the ICU while reliably performing in critically ill patients for up to 80 hrs. Use of the device did not significantly alter the function or longevity normally expected from a 20-gauge radial artery catheter. We submit that this blood gas monitoring system can replace the use of blood gas analyzers for ICU patients with indwelling arterial catheters. PMID- 8472566 TI - Initial evaluation of a new intra-arterial blood gas system in humans. AB - OBJECTIVE: To evaluate the in vivo performance of a continuous intra-arterial blood gas monitor as compared with in vitro arterial blood gases for measurements of PaO2, PaCO2, and arterial pH. DESIGN: Consecutive patient enrollment. SETTING: Medical intensive care unit of a county teaching hospital. PATIENTS: Five critically ill patients. INTERVENTIONS: All patients had a fiberoptic sensor placed through a 20-gauge cannula inserted into the radial artery. Sensor and arterial blood gas measurements were monitored up to 68 hrs. Arterial blood gases were analyzed on two blood gas analyzers. MEASUREMENTS AND MAIN RESULTS: A total of 104 arterial blood gases were obtained for comparison of sensor measurements with blood gas analyzer values. Comparison of the sensor values with the blood gas analyzer values showed bias and precision values of -0.021 and 0.037 for arterial pH, 1.74 and 6.06 torr (0.23 and 0.81 kPa) for PaCO2, and -5.89 and 13.19 torr (-0.79 and 1.76 kPa) for PaO2, respectively. Comparison of the two blood gas analyzer measurements showed bias and precision values of -0.030 and 0.010 for arterial pH, 1.96 and 2.55 torr (0.26 and 0.34 kPa) for PaCO2, and 5.77 and 17.15 torr (-0.77 and 2.29 kPa) for PaO2, respectively. No complications attributable to the sensor were detected. CONCLUSIONS: The performance of this fiberoptic continuous intra-arterial blood gas monitor is comparable to that of blood gas analyzers and compares favorably with previously reported studies utilizing other sensors in reliably and reproducibly approximating PaO2, PaCO2, and arterial pH values. This monitoring capability was accomplished with no patient morbidity. Further study is indicated to confirm these initial results and to establish the role of a continuous intra-arterial blood gas monitor in critically ill patients. PMID- 8472567 TI - A clinical evaluation of a blood conservation device in medical intensive care unit patients. AB - OBJECTIVES: This study was designed to a) document the efficacy of a device intended to conserve blood in critically ill patients; b) determine the effect of this blood conservation on hemoglobin concentration and the need for blood transfusions; c) determine if the blood conservation device resulted in interference with arterial pressure waveforms; d) determine if use of the blood conservation device resulted in a difference in the number of accidental needle punctures suffered by healthcare workers. DESIGN: Prospective, randomized, controlled trial. A clinical trial using prospective, random allocation of consecutive eligible patients. SETTING: The medical intensive care unit (ICU) of a university hospital located in a large metropolitan area. PATIENTS: A total of 100 patients who were admitted to the medical ICU, required arterial line monitoring for clinical purposes, and were managed by the ICU medical service. Exclusion criteria included active bleeding or chronic renal failure at the time of ICU admission. INTERVENTIONS: Patients in the experimental group had a blood conservation device incorporated into the arterial pressure monitoring system, while patients in the control group received a conventional arterial pressure monitoring system. MEASUREMENTS AND MAIN RESULTS: Data gathered included: age; gender; ICU discharge status; the duration of ICU stay; time in the study; volume of all blood drawn, discarded, or lost due to leakage; hemoglobin concentrations; blood transfusions; and accidental needle injuries. Arterial pressure waveforms were recorded and inspected for dampening or other deformation. Mean hemoglobin concentrations were compared on ICU admission and at 12-hr intervals. Demographic and clinical characteristics of the two groups were not significantly different. The volume of blood drawn and discarded from arterial catheters was significantly lower in the blood conservation group (blood conservation device: 5.7 +/- 7.5 mL; control: 96.4 +/- 88.5 mL; p < .0001), as was the total volume of blood discarded (blood conservation device: 19.4 +/- 47.4 mL; control: 103.5 +/- 99.9 mL; p < .0001). Mean hemoglobin concentration on admission was similar in the two groups (blood conservation device group: 11.8 +/- 2.5 g/dL; control group: 12.6 +/- 2.3 g/dL). In both groups, the mean hemoglobin concentration declined most rapidly in the first 24 hrs of ICU care and, thereafter, declined more slowly. Although the mean hemoglobin concentration was higher in the blood conservation group after 6 days, statistical significance was not reached until 9.5 days of ICU care. The mean change in hemoglobin concentration (overall: 1.2 +/- 2.2 g/dL) during the study represents a statistically significant (p < .0001) decrease of 9.7%. Hemoglobin concentration during the study decreased by 1.4 +/- 2.2 g/dL in the control group and 1.0 +/- 2.3 g/dL in the blood conservation group (p = nonsignificant). Univariate and multiple regression analysis demonstrated discarded blood volume to be a significant and independent predictor of the decline in hemoglobin concentration. Transfusion requirements were similar in both groups. The blood conservation system did not alter or interfere with pressure waveforms. There were no accidental needle injuries noted. CONCLUSIONS: The conservation of blood in critically ill patients must be a high-priority concern of all healthcare workers. Our data indicate that the blood conservation system eliminates a significant factor in the decline in hemoglobin concentration. With devices as described here, there is no reason to continue the practice of wasting the blood of critically ill patients in order to prevent preanalytic error. PMID- 8472568 TI - Evaluation of a new blood-conserving arterial line system for patients in intensive care units. AB - OBJECTIVE: To evaluate blood samples obtained from a new blood-conserving arterial line system for the presence of hemodilution or heparin contamination. DESIGN: Prospective, clinical trial. SETTING: A coronary intensive care unit in a tertiary-care teaching hospital. PATIENTS: Cardiovascular patients in whom invasive arterial blood pressure monitoring was indicated. INTERVENTIONS: Paired blood samples were obtained from a conventional arterial line system and a new blood-conserving arterial line system for the measurement of hematocrit and partial thromboplastin time, and compared to evaluate for the presence of either hemodilution or heparin contamination. MEASUREMENTS AND MAIN RESULTS: A Bland Altman bias analysis of the variability between the two blood draw methods was performed. The analysis indicated that a) a randomly determined partial thromboplastin time obtained from the blood-conserving arterial line would lie between 3.32 and -5.11 of the partial thromboplastin time taken from the conventional arterial line value with 95% confidence; and b) a randomly determined hematocrit obtained from the blood-conserving arterial line would lie between 1.97 and -1.85 of the hematocrit taken from the conventional arterial line value with 95% confidence. CONCLUSIONS: We concluded that a) blood samples obtained with the blood-conserving arterial line demonstrate no evidence of hemodilution or heparin contamination; b) the blood-conserving arterial line provides blood samples without the need for an initial volume of blood to be discarded; c) the blood-conserving arterial line provides a means for blood conservation in the intensive care setting. PMID- 8472569 TI - Verbal communication of ventilator-dependent patients. AB - OBJECTIVE: To assess whether communication capabilities of ventilator-dependent patients are improved by the use of the Passy-Muir unidirectional valve. DESIGN: Prospective study. SETTING: An 18-bed multidisciplinary intensive care unit (ICU) at the University Hospital, Las Palmas, Spain. PATIENTS: Ten chronic ventilator dependent patients who had undergone tracheostomy and met the following criteria: ability to eliminate tracheobronchial secretions in order to maintain a patent and unobstructed airway, adequate gas exchange while ventilated with an FIO2 of < or = 0.4 (Pao2 > 60 torr [8 kPa]), Paco2 of < 55 torr (7.3 kPa), normal hemodynamics without the need for administration of vasopressors, and normal mental state. Eight patients presented with pulmonary disease, and two presented with neuromuscular disease. INTERVENTIONS AND METHODS: Before attaching the Passy Muir valve, the following procedures were performed: a) suction of tracheal and pharyngeal secretions; b) deflation of the tracheostomy tube cuff; c) increase in the ventilator's tidal volume setting to maintain the inspiratory pressure before cuff's deflation; d) set peak inspiratory pressure alarm and disconnect expiratory volume alarm. The valve was then connected between the tracheostomy tube and the Y-shaped piece of the ventilator's circuit. Respiratory movements, arterial blood gases, peak inspiratory pressure, respiratory rate, quantity of secretions, and changes in sense of smell were monitored during the study. The valve's efficacy was evaluated according to the patient's ability to talk and be understood during the entire respiratory cycle. RESULTS: The Passy-Muir valve was effective in improving communication in eight of ten patients who, during its use, presented insignificant cardiorespiratory changes, decreased secretions, and effected considerable improvement in well-being. Its use was impossible in two patients: one with severe pulmonary disease because cuff deflation prevented adequate ventilation, and one patient with neuromuscular disease and laryngopharyngeal dysfunction. CONCLUSIONS: The Passy-Muir unidirectional valve allows ventilator-dependent patients to talk and communicate without assistance. Patients felt better and were motivated to participate in their own care. PMID- 8472570 TI - Massive airway leaks: an analysis of the role of endotracheal tubes. AB - OBJECTIVE: To determine the abnormalities present in endotracheal tubes removed from mechanically ventilated patients for "massive airleak." "Massive airleak" was defined as a leak that the attending physician felt was indicative of endotracheal tube defect such that extubation (and reintubation, if needed) would be indicated. DESIGN: Prospective, observational study. SETTING: Mixed medical surgical intensive care unit at a community teaching hospital. PATIENTS: Seventeen patients among 1,082 patients who were undergoing mechanical ventilation during the study period. INTERVENTIONS: Authors were not involved in the evaluation of most airleak situations and most participating physicians were unaware of the study. All physicians involved were board certified in pulmonary, critical care, emergency medicine, or anesthesiology. Removed endotracheal tubes were grossly inspected and subjected to pneumatic stress to determine the sites of the leakage. MEASUREMENTS AND MAIN RESULTS: Eighteen endotracheal tubes were examined over a 2-yr period. Of these tubes, 11 (61%) had no evidence of mechanical fault. Five (28%) tubes had defects in the tracheal cuff and two (11%) tubes had abnormalities of the pilot valve apparatus. Condensation within the pilot valve cuff was present in 14 of 18 tubes and was present in ten of 11 intact tubes. Although the study population had an equal number of orally and nasally placed endotracheal tubes, intact tubes were disproportionately oral (8/11) and tubes wtih cuff leaks were predominantly nasal (4/5) (p = .038). CONCLUSIONS: A large number of endotracheal tubes removed for presumed defect are flawless. The authors speculate that tube malposition is the most likely explantation for this phenomenon. Our findings suggest that patient care might improve with more meticulous daily attention to the airway, as well as a more analytical rather than action-oriented approach to the leaking endotracheal tube. PMID- 8472571 TI - Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients. AB - OBJECTIVE: To determine whether continuous veno-venous hemofiltration with dialysis leads to extraction of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and removal rates of these cytokines and their effect on serum cytokine concentrations. DESIGN: Prospective, controlled study of TNF-alpha IL-1 beta extraction by continuous veno-venous hemofiltration with dialysis in patients with septic acute renal failure. SETTING: Intensive care unit of a tertiary institution. PATIENTS: Eighteen critically ill patients with sepsis and acute renal failure. Control group of six patients experiencing an acute illness while undergoing chronic hemodialysis. INTERVENTIONS: Collection of blood samples before continuous veno venous hemofiltration with hemodialysis. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 hrs of treatment. MEASUREMENTS AND MAIN RESULTS: TNF-alpha and IL-1 beta concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extraction were calculated and compared with a control group. TNF-alpha was detected in 66.6% of serum samples of patients with septic acute renal failure; IL-1 beta was detected in 55% of patients' sera samples. Both TNF-alpha and IL-1 beta were cleared by the hemofilter during continuous veno-venous hemofiltration with dialysis. The mean clearance for TNF-alpha was 30.7 L/day (95% confidence interval 22.4 to 39) with a daily mean excretion of 14.1 micrograms (95% confidence interval 1.7 to 26.5). Mean IL-1 beta clearance was 36.1 L/day (95% confidence interval 25.4 to 46.8) equivalent to a mean daily IL-1 beta excretion of 1 microgram (95% confidence interval 0.9 to 1.1). No measurable concentrations of TNF-alpha or IL-1 beta were found in the serum or ultrafiltrate specimens of control patients. CONCLUSIONS: These findings demonstrate that continuous veno-venous hemofiltration with dialysis can remove both TNF-alpha and IL-1 beta from the circulation of septic, critically ill patients. This cytokine extraction may prove to be of benefit in attenuating the progression of multiple organ dysfunction in patients with sepsis associated renal failure, who are receiving continuous veno-venous hemofiltration with dialysis. This potential benefit of existing hemofiltration therapies supports their preferential implementation in patients with renal failure associated with severe sepsis. These observations may stimulate the modification of filtration membrane design seeking to specifically augment the clearance from the circulation of a variety of such cytokines. PMID- 8472572 TI - Evaluation of gastric emptying in severe, burn-injured patients. AB - OBJECTIVE: The aim of this study was to evaluate the possible effect of a severe burn on gastric emptying by determining the absorption kinetics of orally administered acetaminophen. DESIGN: A prospective, controlled study. SETTING: A ten-bed burn center in a 1,300-bed university hospital. PATIENTS: Ten adult patients suffering from second-degree burn involving > 20% of total body surface area and 20 normal, healthy volunteers who acted as controls. INTERVENTIONS: Patients received routine treatment such as nutritional support and cimetidine. However, opiates were stopped for at least 12 hrs before the start of the study, and nonsteroidal anti-inflammatory drugs as alternatives were used. After an 8-hr fast, the subjects ingested 0.5 g acetaminophen with 200 mL of water. The plasma concentrations of acetaminophen were determined by high-performance liquid chromatography, and the absorption kinetics was estimated from determination of time to reach the maximum plasma concentration, the maximum plasma concentration, and the area under the plasma concentration-time curve. MEASUREMENTS AND MAIN RESULTS: The mean time for reaching the maximum plasma concentration was 33 +/- 24 (SD) mins in patients and 39 +/- 24 mins in the healthy volunteers. The mean area under the plasma concentration-time curve from time 0 to 120 mins and the mean maximum plasma concentration were 556 +/- 190 micrograms/mL/min and 9.5 +/- 3.5 micrograms/mL in patients, and 539 +/- 131 micrograms/mL/min and 7.8 +/- 2.8 micrograms/mL in volunteers, respectively. There was no statistical difference between groups in the time to reach the maximum plasma concentration, the area under the plasma concentration-time curve from time 0 to 120 mins, and the maximum plasma concentration. The time for reaching the maximum plasma concentration was not correlated with the severity of the burn (% area of burn) and the duration of healing (days) after burn. CONCLUSIONS: We conclude that severe burn injury does not affect the kinetics of gastric emptying, and that 200 mL of water ingested 2 hrs before anesthesia is quite safe in severely burned patients. Also, the absorption kinetics of acetaminophen was not altered by burn injury. PMID- 8472573 TI - Usefulness of atrial electrograms recorded via central venous catheters in the diagnosis of complex cardiac arrhythmias. AB - OBJECTIVE: To assess the role of intravascular atrial electrograms in improving the diagnosis of complex cardiac arrhythmias in critically ill patients. DESIGN: Prospective, clinical study comparing the accuracy of cardiac rhythm diagnosis using standard surface electrocardiogram (EKG) and intravascular atrial electrograms. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: A total of 57 critically ill patients (44 cardiothoracic surgery, five acute myocardial infarction, two septic shock, six miscellaneous) with 85 complex cardiac arrhythmias that were unable to be diagnosed with certainty using the surface EKG. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The intravascular atrial electrogram altered diagnosis based on the surface EKG in 11 (13%) patients and confirmed rhythm diagnosis in 60 (71%) of 85 patients with arrhythmia. Of 61 patients with wide complex tachycardia, 40 (66%) were diagnosed as ventricular tachycardia (atrioventricular dissociation demonstrated on the atrial electrogram), and 11 (18%) as supraventricular tachycardia with aberrant conduction. Ten (16%) wide complex tachycardias could not be diagnosed with confidence using both surface EKG and intravascular electrogram. There were no adverse effects with this technique. CONCLUSIONS: Intravascular atrial electrograms recorded via central venous catheters are useful in the diagnosis of complex cardiac arrhythmias, particularly ventricular tachycardia. The technique is safe, simple, and quick. PMID- 8472574 TI - Endocrine profiles for outcome prediction from the intensive care unit. AB - OBJECTIVE: To evaluate the discriminating ability of various specific endocrine studies on patient outcome from the intensive care unit (ICU). DESIGN: Prospective cohort study of patients requiring intensive care. SETTING: Adult medical and coronary care units in a military referral hospital. PATIENTS: A total of 61 consecutive patients requiring intensive care over a 5-month period and 20 control subjects. INTERVENTIONS: Patients were evaluated within 24 hrs of ICU admission (day 1) with determination of the following variables: serum triiodothyronine, thyroxine, triiodothyronine resin uptake, thyrotropin, luteinizing hormone, follicle-stimulating hormone, testosterone, basal cortisol, adrenocorticotropic hormone-stimulated cortisol, cortisol increment, and Acute Physiology and Chronic Health Evaluation (APACHE II) score. A total of 24 hrs later (day 2), the same battery of tests was repeated with the exception of the adrenocorticotropic hormone-stimulated cortisol, cortisol increment, and APACHE II score. Individual variables were compared between survivors and nonsurvivors. MEASUREMENTS AND MAIN RESULTS: The best discriminators of patient outcome in descending order were the basal serum cortisol and triiodothyronine concentrations obtained on day 2 and the APACHE II score with predictive abilities of 81%, 74%, and 70%, respectively. No combination of variables was superior to the day 2 basal cortisol concentration for discrimination of outcome. CONCLUSIONS: The basal cortisol and triiodothyronine concentrations obtained from blood samples collected within 48 hrs of ICU admission appear to be better discriminators of patient outcome than the APACHE II score. PMID- 8472575 TI - Alteration of taurine homeostasis in acute heatstroke. AB - OBJECTIVE: To investigate the potential role of taurine as a hypothermic modulator during heatstroke. DESIGN: Prospective analyses. SETTING: Heatstroke Center in makkah, Saudi Arabia. PATIENTS: Twenty-nine adult patients with heatstroke. INTERVENTIONS: High-performance liquid chromatography was used to measure plasma and urine taurine concentrations in heatstroke patients on admission (precooling) and 24 hrs after complete cooling (postcooling). MEASUREMENTS AND MAIN RESULTS: There were 18 males and 11 females with a mean rectal temperature of 42.2 +/- 0.14 degrees C. At the precooling time period, the taurine concentrations were increased (plasma 180 +/- 14 mumol/L; urine 4142 +/- 720 mumol/L [normal ranges 45.5 to 138.2 and 168 to 1890 mumol/L, respectively]). At the postcooling time period, taurine concentrations were significantly (p < .0001) decreased (54 +/- 6 and 802 +/- 160 mumol/L for plasma and urine, respectively). No correlation was found between taurine and creatine kinase activity, or between precooling temperature and taurinemia or taurinuria. CONCLUSIONS: The source and clinical significance of the increased taurine concentrations are to be determined. The involvement of taurine in the regulation of core body temperature suggests that it may have an adaptive role in heatstroke. PMID- 8472576 TI - Physiologic variables and fluid resuscitation in the postoperative intensive care unit patient. AB - OBJECTIVE: To examine how critical surgical illness and its management alter some of the biochemical, physiologic, and hematologic parameters commonly used to monitor postoperative, critically ill patients. DESIGN: Prospective survey of 150 patients over 3 months. SETTING: University hospital surgical intensive care unit. PATIENTS: A total of 150 consecutive adult patients admitted to the surgery anesthesiology intensive care unit. MATERIALS AND METHODS: The effects of surgery on serum albumin and total protein concentrations, and lymphocyte counts were investigated. This investigation was done by comparing the values before surgery with those values after surgery and by also comparing what happened after different types of surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After surgery, decreases in serum albumin concentrations were significantly related to the estimated blood loss and acute gain in body weight from intravenous fluid resuscitation. The decreases in serum albumin and total protein concentrations were greater after elective abdominal surgery than after elective thoracic surgery. Total lymphocyte counts were significantly (< 1000 cells/mm3) reduced only in patients undergoing abdominal surgery. CONCLUSIONS: Serum albumin and total protein concentrations and total lymphocyte counts were significantly reduced by surgical injury, with significantly greater decreases seen after abdominal than thoracic surgery. These decreases were caused, in large part, by the volume of intravenous fluid used in resuscitation and blood loss. The changes in these variables are thus dependent on the type of surgical stress and the perioperative fluid therapy. PMID- 8472577 TI - Adaptation of pressure support ventilation to increasing ventilatory demand during experimental airway obstruction and acute lung injury. AB - OBJECTIVE: To estimate the changes in the relative amount of ventilatory assistance offered by inspiratory pressure support during changing ventilatory demand with external airway obstruction and with oleic acid-induced acute lung injury. DESIGN: Prospective, controlled, crossover study. SETTING: Experimental laboratory in a university anesthesiology department. SUBJECTS: Eight dogs anesthetized with pentobarbital. INTERVENTIONS: An external resistor was placed in the breathing circuit to produce increased resistance to breathing. Acute lung injury was produced with oleic acid. Ventilatory demand was increased by increasing the CO2 concentration in inspired gas to produce an increase of 20 torr (2.7 kPa) in end-tidal CO2 tension. During airway obstruction, pressure support was adjusted to reduce the inspiratory decrease in intrathoracic pressure to the level present during unobstructed breathing. During acute lung injury, pressure support was applied to reduce the maximum negative deflection of intrathoracic pressure by 50%. MEASUREMENTS AND MAIN RESULTS: The ventilator effort was estimated by calculating the pressure-time integral of proximal airway pressure; the spontaneous ventilatory effort was estimated in a similar manner from esophageal pressure. The pressure support averaged 10 +/- 3 cm H2O during airway obstruction and 7 +/- 2 cm H2O during lung injury. The CO2 challenge effected an average increase in mean minute ventilation of 78% during airway obstruction (p < .001) and 120% during acute lung injury (p < .01). The augmentation of minute ventilation was accomplished by increasing the ventilatory rate and the transpulmonary pressure while inspiratory time remained unchanged. The pressure-time integrals measured using both airway (p < .001) and esophageal pressure (p < .01) increased significantly during each CO2 challenge, reflecting an increase in the contribution of both the ventilator and the animal to the required breathing effort. Significant decreases in the relative magnitude of the ventilator effort both during airway obstruction (p < .05) and during lung injury (p < .01) indicated that the increase in the spontaneous effort was predominant over the increase in mechanical ventilatory support. CONCLUSIONS: A ventilatory rate-dependent adaptation of pressure support to increased ventilatory demand occurs in an experimental setting both during airway obstruction and lung injury. The results of this study confirm an advantage of breath-to-breath inspiratory pressure support over techniques designed to supply a predetermined mechanical minute volume. PMID- 8472578 TI - Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone. AB - OBJECTIVE: To study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DESIGN: Prospective randomized, controlled study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Twelve adult New Zealand white rabbits. INTERVENTIONS: Respiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. MEASUREMENTS AND MAIN RESULTS: Before and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 +/- 7 torr [8.2 +/- 0.9 kPa] to 470 +/- 47 torr [62.6 +/ 6.2 kPa]) and in functional residual capacity (7.6 +/- 1.4 to 17.7 +/- 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. CONCLUSIONS: The findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance. PMID- 8472579 TI - Cocaine significantly impairs myocardial relaxation. AB - OBJECTIVES: To determine the immediate effects of intravenous "recreational" doses of cocaine on myocardial ventricular relaxation and contraction and on coronary blood flow. To determine the cardiac effects of cocaine after the administration of propranolol, as propranolol has been used to limit the cardiovascular effects of cocaine. DESIGN: Prospective study. SUBJECTS: Twenty mongrel dogs. INTERVENTIONS: We continuously recorded central aortic pressure, left atrial and ventricular pressures, coronary artery blood flow, and electrocardiograms in each dog. We determined from the left ventricular pressure waveforms the maximum rate of pressure increase [(dP/dt)max] and the time constant of isovolumic ventricular relaxation as our indices of ventricular contraction and relaxation. MEASUREMENTS AND MAIN RESULTS: In our initial series of experiments, we obtained pressure, coronary artery blood flow, and electrocardiographic recordings in ten anesthetized dogs before and for 40 mins after the intravenous administration of cocaine, in doses of 2.5 and then 5 mg/kg. In our second series of experiments in ten additional dogs, we injected 0.5 mg/kg of propranolol intravenously 30 mins before the injection of cocaine (2.5 mg/kg), and obtained hemodynamic and electrocardiographic recordings before and for 40 mins after the injection of propranolol and cocaine. Cocaine, 2.5 mg/kg, abruptly increased the time constant of isovolumic ventricular relaxation from 22.9 +/- 1.2 to 29 +/- 2.2 msecs at 1 min (p < .05) and to 35.3 +/- 2 msec at 40 mins (p < .01) but did not significantly change the mean arterial pressure, left atrial pressure, heart rate, coronary blood flow, or the maximum rate of left ventricular pressure increase [(dP/dt)max]. Cocaine also progressively displaced the electrocardiographic ST segments by 3.2 +/- 0.6 mm (p < .01) over 40 mins. Cocaine, 5 mg/kg, rapidly increased the time constant of isovolumic ventricular relaxation from 28.5 +/- 2.5 to 41 +/- 3 msecs in 1 min (p < .05) and to 48.7 +/- 4 msecs at 40 mins (p < .01) and reduced (dP/dt)max from 2905 +/- 370 to 1422 +/- 121 mm Hg/sec at 1 min (p < .01); (dP/dt)max returned to 2351 +/- 415 mm Hg/sec during the next 39 mins. Cocaine did not significantly change either the mean arterial or left atrial pressures. However, this dose of cocaine did decrease, over 40 mins, the heart rate from 184 +/- 11 to 139 +/- 11 beats/min (p < .01) and reduced coronary blood flow by 20% (p < .01). Cocaine also displaced the electrocardiographic ST segments by 3.3 mm over 40 mins (p < .05). Cocaine and propranolol abruptly increased the time constant of isovolumic ventricular relaxation from 26.4 +/- 1.3 to 43.2 +/- 2.1 msecs (p < .01) at 1 min and to 46.8 +/- 1.5 msecs at 3 mins (p < .01). The time constant of isovolumic ventricular relaxation remained abnormally increased at 43.0 +/- 1.4 msecs at 40 mins. Cocaine and propranolol reduced (dP/dt)max from 2760 +/- 458 mm Hg/sec to a minimum value of 1400 +/- 119 mm Hg/sec at 2 mins (p < .01). However, (dP/dt)max then returned to 2201 +/- 359 mm Hg/sec during the next 38 mins. Cocaine and propranolol did not significantly change the mean arterial and left atrial pressures, or heart rate, but did reduce coronary blood flow, over 40 mins, by 25% (p < .001). Cocaine also maximally displaced the electrocardiographic ST segments by 1 +/- 0.2 mm (p < .01). CONCLUSIONS: Cocaine substantially impairs myocardial ventricular relaxation for periods of at least 40 mins. Propranolol significantly intensifies cocaine's depressant effect on ventricular relaxation. PMID- 8472580 TI - Indicator amount, temperature, and intrinsic cardiac output affect thermodilution cardiac output accuracy and reproducibility. AB - OBJECTIVE: To determine the accuracy and reproducibility of four thermodilution indicators (5-mL room temperature, 10-mL room temperature, 5-mL iced, and 10-mL iced injectates) at clinically relevant flow rates. DESIGN: Quasi-experimental study. SETTING: Animal research laboratory of a health sciences university. SUBJECTS: Six virgin western-breed ewes. INTERVENTIONS: Data were collected from six ewes that had ascending aorta electromagnetic flow probes and inferior vena cava occluders. Cardiac output was manipulated by inferior vena cava occlusion and isoproterenol infusion. Four thermodilution indicators were tested at high and low levels of cardiac output and compared with the electromagnetic flowmeter measurements of cardiac output. MEASUREMENTS AND MAIN RESULTS: The indicator amounts were determined from both injectate volume and temperature difference between the injectate and blood. Using 5-mL room temperature injectate as a reference, 10-mL room contained 2 x, 5-mL iced 2.1 x, and 10-mL iced 4.1 x the indicator amount of 5-mL room temperature injectate. Approximately 210 simultaneous thermodilution and electromagnetic flow measurements were made for each injectate over a flow range of 1.5 to 15.7 L/min. For the entire cardiac output range, systematic error was not present. However, the r2 value (.92) for the 10-mL iced injectate group was greater (p < .05) than that value (.79) for the 5-mL iced injectate group, while r2 values were .79 for the 10-mL room temperature group and .49 for the 5-mL room temperature group. At flow rates of < 4.7 L/min, r2 was not different among injectates, but reduced indicator amounts progressively overestimated output (p < .05), reaching 21% for the 5-mL room temperature group. At flow rates of > 7.7 L/min, the r2 value (.81) for the 10-mL iced group was greater (p < .05) than that value (.45) for the 5-mL iced group, while r2 values were .24 for the 10-mL room temperature group and .08 for the 5 mL room temperature group. Systematic error was not present. CONCLUSIONS: At low cardiac output levels, reduced indicator impairs accuracy but not reproducibility, a phenomenon that is perhaps related to indicator loss. At high cardiac output rates, reduced indicator impairs reproducibility. This phenomenon is probably related to low signal-to-noise ratio. Thermodilution indicator amounts should be tailored to the output range. PMID- 8472581 TI - Civilian triage in the intensive care unit: the ritual of the last bed. AB - OBJECTIVE: To evaluate the numerous problems that exist when there is an acute shortage of trained critical care nurses, no triage officer is available or designated, there is no cooperation among intensive care units (ICUs) or alternative sites, or there is excessive political or financial pressure applied to maintain a referral practice or to fill all the beds, or limited ability to divert ambulances to other hospitals. The Joint Commission on Accreditation of Health Care organizations now mandates a written policy: "when patient load exceeds optimal operational capacity" (1992). DATA SOURCES/STUDY SELECTION: Selected clinical, philosophical, and public policy literature on the subject of triage. DATA SYNTHESIS/DATA EXTRACTION: 1) An ICU medical director, designee, or supervisory nurse should be empowered as the gatekeeper/triage officer. 2) The basis for regulating admission, discharge, or triage from the special care unit should be medical suitability (from a utilitarian or egalitarian point of view). During high-level triage when all ICU patients are receiving active therapy, these decisions should override the individual primary physician-patient relationship. 3) The guidelines should follow the "congestive heart failure" treatment analogy: a) preload reduction: hold high-risk patients in the postanesthesia care unit or Emergency Room, postpone surgery, hold transfers in outlying ICUs; b) improve cardiac performance: increase efficiency and decrease workload per patient by performing fewer invasive procedures and transporting fewer patients for abdominal computed tomography scans; c) afterload reduction: keep unstable patients in the postanesthesia care unit, send sicker patients to intermediate care units, send "stable" ventilator-dependent patients to general medical/surgical units, and transfer or resolve issues regarding "hopeless" patients. CONCLUSIONS: It is necessary to have public disclosure of the broader issues related to high-level triage. The first issue is recognition that there are periods of time when ICU capacity is exceeded or skilled critical care nurse availability is reduced. The next issue is the decision of who is best suited to make complex and dynamic triage decisions and what kind of oversight should be provided. Other issues relate to whether there should be patient or family consent, and what to do about patients receiving marginal benefit or who are considered hopeless or unsalvageable, yet the family or surrogate decision maker (or perhaps one of the consultants) wants to continue active care in the ICU. In the conflict between individual and community rights and benefits, there should be a nonlitigious approach when a patient is harmed during these periods of high census or limited capacity. In recognition of these complex issues (including potential conflicts among ICUs, hospital administration, individual physicians, and the various medical and surgical programs feeding patients into special care units), the Society of Critical Care Medicine has organized a Task Force on the legal and ethical justification for triage. PMID- 8472582 TI - Pediatric intensive care units: results of a national survey. AB - OBJECTIVE: To describe the structure and organization of pediatric intensive care units (ICUs) in the United States. SURVEY METHODS: We directed a mail survey to pediatric ICU medical and nursing directors and hospital quality assurance officers. A total of 201 of 301 hospitals with pediatric ICUs initially responded. Telephone confirmation of the mail survey (n = 193) and telephone data collection for mail survey nonresponders (n = 42) were also undertaken. SURVEY RESULTS: The largest proportion (40.0%) of pediatric ICUs had four to six beds per unit, while only 6.0% had > 18 beds per unit. The admissions per year averaged 528 +/- 24, and the mortality rates averaged 5.5 +/- 0.2%. Only 79.6% of the pediatric ICUs had full-time medical directors. A pediatric intensivist was available to 73.2% of the units. Physician coverage for 24 hrs/day dedicated only to the pediatric ICU was present in 48.5% of hospitals. As ICU size increased, the estimated mortality rates increased, as did the percentages with full-time directors, pediatric intensivists, and 24 hrs/day dedicated coverage. Medical school affiliation existed for 79.6% of pediatric ICU hospitals, and 81.1% of these hospitals were the primary teaching program sites for pediatrics. Other ICUs caring for children were present in 30.2% of the hospitals. SURVEY APPLICATION: The mail survey respondents were stratified using four factors: size, teaching status, intensivist status, and coordination of care status. A total of 16 respondents were randomly selected for an ongoing outcomes study of the importance of these factors. CONCLUSIONS: Substantial diversity exists in pediatric ICU structure and organization. Determining factors associated with quality of care is important for improving outcomes. PMID- 8472583 TI - A model for technology assessment applied to pulse oximetry. The Technology Assessment Task Force of the Society of Critical Care Medicine. AB - OBJECTIVES: To test a model for the assessment of critical care technology. To develop practice guidelines for the use of pulse oximetry. DATA SOURCES: A computer-assisted search of the English language literature and interviews with recognized experts in the field of pulse oximetry. STUDY SELECTION: Those studies that addressed one or more of the seven questions contained in our technology assessment template were analyzed. Study design was not a factor in article selection. However, the lack of well-designed clinical outcome studies was an important factor in determining the method of practice policy development we utilized. DATA EXTRACTION: A focus person summarized the data from the selected studies that related to each of the seven assessment questions. The preliminary data summary developed by the focus person was further analyzed and refined by the task force and then sent to 16 expert reviewers for comment. These expert comments were considered by the task force, and this final consensus report was developed. DATA SYNTHESIS: Pulse oximetry combines the principles of spectrophotometry and plethysmography to noninvasively measure oxygen saturation with a high degree of accuracy over the range of 80% to 100% saturation, assuming the device is being used according to the manufacturer's instructions and without any adverse operating conditions. The appropriate clinical uses of pulse oximetry fall into one of two broad categories: as a warning system based on continuous real-time measurement of arterial desaturation, or as an end-point for titration of therapeutic interventions. There are no published studies that allow for definitive, outcome-based conclusions concerning either the clinical impact or cost-benefit ratio of pulse oximetry. CONCLUSIONS: The model developed for technology assessment proved to be appropriate for assessing pulse oximetry. The available data have allowed us to develop an evidence-based practice policy for the use of pulse oximetry in critical care. Critical care clinicians, researchers, and industry have a shared responsibility to provide valid outcome and efficacy studies of new technologies. PMID- 8472584 TI - Extracorporeal membrane oxygenation support for cardiac dysfunction from tricyclic antidepressant overdose. PMID- 8472585 TI - Late presentation of misalignment of lung vessels with alveolar capillary dysplasia. PMID- 8472586 TI - Sensory evoked potentials accurately predict recovery from prolonged coma caused by strangulation. PMID- 8472587 TI - Relative humidity not absolute humidity is of great importance when using a humidifier with a heating wire. PMID- 8472588 TI - Electrical power failure in a cardiothoracic intensive care unit. PMID- 8472589 TI - Electrical power failure in a cardiothoracic intensive care unit. PMID- 8472590 TI - Mammography: breast implants--types, complications, and adjacent breast pathology. AB - Approximately 1.5 million women in the United States currently have breast implants. The majority were placed for cosmetic augmentation, but 20% were placed for reconstruction after the loss or deformity of a breast. The augmented breast is a challenge to the mammographer. Many of the palpable and mammographically detected abnormalities in these patients are related to the implant itself. Since, however, there is breast tissue present with cosmetic augmentation, the full range of fibrocystic and neoplastic conditions that can affect the breast may be seen. The presence of the implant makes imaging the breast more difficult because the implant obscures the nearby breast tissue. This paper reviews the history and evolution of various breast prostheses. The surgical approaches to placement of implants and complications associated with their use will be discussed. Examples of concomitant pathologies and a review of imaging strategies will be given. PMID- 8472591 TI - Cervical lymph node metastasis. PMID- 8472592 TI - Predictors of mortality, COPD morbidity, and respiratory cancer--with special reference to respiratory symptoms, lung function, and occupational exposure cement dust. PMID- 8472593 TI - Elastolytic activity of human monocytes. With special reference to rheumatoid arthritis and giant cell arteritis. PMID- 8472594 TI - Xamoterol--a beta-1-adrenoceptor partial agonist. Pharmacology and clinical use. PMID- 8472595 TI - Reliability in perinatal audit. A qualitative study--a preliminary investigation. AB - The aim of this study was to elucidate some aspects of reliability in perinatal audit, both by describing aspects of the ways in which consensus is reached between experts in perinatal audit and by examining the extent of agreement between two separate panels assessing peri- and neonatal care in 17 cases of neonatal deaths. The consensus process was elucidated by a questionnaire answered by 16 perinatal experts who had participated in a perinatal audit and by analyses of audiotapes. In 70-95% of the cases, most of the experts had reached the same conclusions during their work at home as the panel did after the joint discussions. The audiotapes revealed that the experts adjust their individual interpretations during discussions with other experts. Agreement in evaluation between two panels was elucidated by agreement in evaluation of the quality of antenatal care, intrapartum care, and neonatal care in the 17 cases of neonatal deaths. The two panels agreed in evaluation of antenatal care in 15 cases, in intrapartum care in 14 cases, and in neonatal care in 15 cases. Although the material is small, our results seem to indicate that the conclusions drawn in perinatal audit are reliable when the experts have detailed knowledge of the structure of perinatal and neonatal care, when there are agreed standards of satisfactory care, and when they have the possibility of adjusting their individual interpretations during discussion with other experts. PMID- 8472596 TI - Do specialists give special antibiotic treatment? AB - The use of antibiotics is increasing with increasing ecological and economic problems as a consequence. In Denmark, antibiotics are prescribed by doctors and in order to intervene, it is important to know details about prescription habits. Danish patients are referred to specialists by their general practitioner when further investigation or treatment is needed. In one week in 1988, 180 specialists (60%) participated in a study registering all prescriptions made by these specialists. Only 3.2 patients per specialist were treated with antibiotics. The infections were mainly of the upper respiratory tract, the skin, or gynecological. The prescribed daily dosages (PDD) did not differ from those given by the general practitioners, but the specialists used significantly less penicillin and significantly more erythromycin, tetracycline or local antibiotics. Compared with the general practitioners the specialists in Denmark only prescribed approximately 10% of the total amount of antibiotics used outside the hospitals. Their contribution to the potential ecological and economic problems caused by antibiotics in Denmark is limited. PMID- 8472597 TI - Regulation and function of host defences in the murine lymphocytic choriomeningitis virus infection. PMID- 8472598 TI - Idiopathic myelofibrosis. Clinical aspects and studies on extracellular matrix metabolism. PMID- 8472599 TI - Proteolytic modification of beta 2-microglobulin in human serum. PMID- 8472600 TI - Normal age-related changes in bone mass, structure, and strength--consequences of the remodelling process. PMID- 8472601 TI - Justification for magnesium therapy in acute ischaemic heart disease. Clinical and experimental studies. PMID- 8472602 TI - Method for counting mitoses by image processing in Feulgen stained breast cancer sections. AB - This study describes an image processing method for the assessment of the mitotic count in Feulgen-stained breast cancer sections. The segmentation procedure was optimized to eliminate 95-98% of the nonmitoses, whereas 11% of the mitoses did not survive the segmentation procedure. Contour features and optical density measurements of the remaining objects were computed to allow for classification. Twelve specimens were analyzed, nine used to serve as a training set, and three put aside for later use as independent test set. The fully automatic image processing method correctly classified 81% of the mitoses at the specimen level while inserting 30% false positives. The automatic procedure strongly correlated with the interactive counting procedure (r = 0.98). Although the fully automatic method provided satisfactory results, it is not yet suited for clinical practice. The automated method with an interactive evaluation step gave an accurate reflection of the mitotic count showing an almost perfect correlation with the results of the interactive morphometry (r = 0.998). Therefore this semiautomated method may be useful as prescreening device. PMID- 8472603 TI - Flow cytometric measurement of [Ca2+]i and pHi in conjugated natural killer cells and K562 target cells during the cytotoxic process. AB - We describe a flow cytometric assay that enables one to follow conjugate formation between cytotoxic cells and their target cells during the cytotoxic process. In addition, the internal calcium concentration ([Ca2+]i) and internal pH (pHi) of the conjugated cells can be monitored and directly compared to the nonconjugated cells. This is achieved by labeling one cell type with the Ca(2+) specific dye Fluo-3, while the other cell type is labeled with the pH-sensitive dye SNARF-1. As these fluorochromes have different emission spectra, events positive for both fluorochromes are identified as conjugates. The results show that the conjugates can be clearly distinguished from single cytotoxic cells [natural killer (NK) cells] and target cells [K562 cells, (TC)]. Upon binding, [Ca2+]i is increased in the NK cells as well as in the TC. In conjugated NK cells this increase of [Ca2+]i is temperature dependent and is followed by a decrease to a normal [Ca2+]i value later on. The [Ca2+]i in NK cells increases in 2 steps, which may be related to the binding--and lethal hit phase. Upon conjugate formation, NK cells show a slight increase in pHi (0.2-0.3 pH units). TC do not reveal a significant change in pHi. PMID- 8472604 TI - Multiparameter flow cytometric analysis of a novel cytotoxin (factor 2) induced tumor cell membrane permeability. AB - An improved twin-probe multiparameter flow cytometric technique was applied to examine a novel cytotoxin, Factor (F2), induced tumor cell permeability. Ability to retain preloaded intracellular bis-carboxyethyl carboxyfluorescein (BCECF, green fluorescence) and to exclude extracellular propidium (red fluorescence) was measured simultaneously with forward and right-angle scatter. In addition to the two expected cell populations which were stained green negative, red positive ("membrane-damaged" and "non-viable", Region 2), and green positive, red negative ("membrane intact" and "viable", Region 3), a third population was seen which fluoresced neither green nor red and displayed intermediate light scatter characteristics (Region 1). K562 cells progressed from Region 3 to Region 1, and then from Region 1 to Region 2 after treatment with F2. These results suggest that sequential changes in membrane structure lead to increased permeability, first with respect to intracellular BCECF and then in turn to extracellular propidium. Flow cytometric changes caused by F2 were detectable 10 min after treatment with 2.5 U/ml of F2, and 5 min after 10 or 40 U/ml of F2. Flow cytometric analysis showed that F2-induced tumor cell lysis and growth inhibition were accompanied by rapid alternations in tumor cell membrane permeability. Flow cytometric analysis also distinguished F2 cytotoxicity from phorbol myristate acetate (PMA) associated cytotoxicity to K562 cells and determined that F2 produced spontaneously or induced by PMA and/or ciprofloxacin had a similar ability to induce tumor cell membrane permeability change. PMID- 8472605 TI - Characterization of hypoxia-dependent peroxide production in cultures of Saccharomyces cerevisiae using flow cytometry: a model for ischemic tissue destruction. AB - Peroxide production in cultures of Saccharomyces cerevisiae was measured using the H2O2-sensitive fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH DA) and flow cytometry. Aeration of cultures of S. cerevisiae exposed to a period of hypoxia was found to induce elevated levels of peroxide that were 100-fold higher than the levels observed in cultures maintained under exclusively aerated or hypoxic conditions. Simultaneous viability analysis, using the fluorescent DNA intercalating dye propidium iodide, indicated that the increase in peroxide generation preceded cell damage and death. Various agents were found to influence the effect of peroxides on cell viability. The addition of ethanol to hypoxic stationary cultures dramatically increased the rate of cell death without further increasing the amount of peroxide produced, while glucose inhibited peroxide production and decreased the rate of cell death. Surprisingly, elevated peroxide levels of hypoxic/reaerated cultures were maintained upon addition of KH2PO4, although the cells remained viable for extended periods of time when compared to control and other test cultures. Similarities between our observations and those of other investigators using anoxic/reperfused organs suggest that hypoxic/reaerated yeast cultures may be a useful model system to study ischemia dependent tissue destruction of mammals. PMID- 8472606 TI - Nationwide quality control trial on lymphocyte immunophenotyping and flow cytometer performance in Italy. AB - The Italian Society for Cytometry (Gruppo Italiano di Citometria, GIC) promoted this nationwide large-scale quality control trial on cellular immunophenotyping and flow cytometer performance in 1991. The aim of this independent study was to evaluate instrument performance with calibrated fluorescence microbeads (minimum threshold for FITC, linearity, coefficients of variation and resolution indexes for fluorescence), and to correlate it to the measurement of lyophilized lymphocyte surface immunofluorescence staining with a wide spectrum of antibodies (percentage of positive cells and fluorescence mean intensity). A single send-out was made to 306 laboratories with 350 instruments throughout Italy. Each kit included anonymous vials containing premixed calibrated microbeads, lyophilized human lymphocytes and small aliquots of conjugated monoclonal antibodies, for both single FITC and double FITC/PE staining. Participants were also asked to use their own anti-CD4 monoclonal. A valid answer was returned by 209 laboratories with 221 instruments. Gating was not an assay variable. The minimum sensitivity threshold for FITC ranged from 26.6 to 11,293 MESF, with marked instrument heterogeneity as far as the relationship between FITC threshold and coefficients of variation for fluorescence was concerned. A low FITC threshold also correlated with a good resolution index for low intensity stainings. No performance comparisons among instrument brands and models were made. The lyophilized lymphocyte analysis showed an overall frequency of outliers ranging from 3.2% to 19.7%, with a maximum for CD2 FITC (19.7%) and CD3 + HLA-DR + (12.1%). A strongly negative relationship was evident between the FITC threshold and the number of CD2+ cells, whereas the sensitivity threshold had virtually no effects on the measured level of higher antigen density markers like CD4 and many others. Absolute fluorescence intensity measurements of CD4+ and CD19+ were also made. This study design proved valid and suitable for a large-scale evaluation of both instrument performance and cytometer operators' skill. A number of practical problems were identified among participants, thus stressing the need for more effective educational programmes and technical guidelines. PMID- 8472607 TI - Evaluation of a dual-color flow cytometry immunophenotyping panel in a multicenter quality assurance program. AB - A basic immunophenotyping panel that employed dual-color combinations of fluorescein isothiocyanate (FITC) and phycoerythrin (PE) conjugated monoclonal antibodies (mAb; FITC-CD45/PE-CD14, FITC-IgG1/PE-IgG2, FITC-CD3/PE-CD8, FITC CD3/PE-CD4, FITC-CD3/PE-CD16 + PE-CD56, and PE-CD19) was utilized in a quality assurance program to determine whether the 4 laboratories participating in a multicenter AIDS study obtained similar lymphocyte subset percentage values for T cells, B cells, NK cells, and CD4+ and CD8+ T cells. Over a 1 1/2 year period, 78 shared peripheral blood specimens were prepared and analyzed in each laboratory. The CD45bright CD14- percentage for each specimen was used to correct that individual's lymphocyte subset values. Interlaboratory coefficients of variation (CV) for the human immunodeficiency virus type I (HIV) seronegative (n = 38) and HIV-seropositive (n = 40) specimens using this panel were < 3% for total T cells; < 5% for CD4+ T cells and CD8+ T cells; < or = 17% for B and NK cells; and < 8% for CD4T/CD8T ratios. The 6-tube basic immunophenotyping panel has several notable features: a) for clinical studies, it permits comprehensive evaluation of an individual's major lymphocyte subsets, i.e., T, B, NK, and CD4+ and CD8+ T cells; b) for interlaboratory proficiency testing programs, it allows the detection of differences among laboratories in measurements of several functionally distinct cell populations; and c) for within-sample quality assurance, it provides several quality control checks, including the lymphosum, i.e., the sum of an individual's corrected T+B+NK values, a sum that was generally 100 +/- 5% on the HIV-seronegative specimens analyzed in this study. PMID- 8472608 TI - Proposal for standardization of flow cytometric reticulocyte maturity index (RMI) measurements. AB - Flow cytometric (FCM) reticulocyte analysis is more accurate, sensitive, and reproducible relative to previously employed manual microscopic methods in clinical laboratory hematology. FCM reticulocyte analysis using RNA binding fluorochromes additionally allows for the quantification of fluorescence intensity or population distribution of the reticulocyte RNA content. Viewed from the perspective of erythroid maturation, quantification of the fluorescence intensity distribution provides a reticulocyte maturation index (RMI). We performed a systematic study of 18 different methods to express thiazole orange stained reticulocyte fluorescence intensity, compared to standard mean fluorescence intensity quantification, using 185 anemic and non-anemic human blood samples. The method best correlating with the mean fluorescence intensity RMI on 2 different FCM instruments (R2 = 0.93 and 0.86) was a ratio of the highly fluorescent reticulocytes, defined using a normal adult population, and the total number of reticulocytes (HFR%). In contrast to mean fluorescence intensity measurements, a HFR% RMI parameter can provide similar units of expression (0.01 1.00) with good correlation between different FCM instruments (R2 = 0.76). We conclude the HFR% method of RMI expression provides a superior means of interlaboratory standardization and clinical comprehension of this useful diagnostic parameter in clinical laboratory hematology. PMID- 8472609 TI - DNA content parameters of paraffin-embedded soft tissue sarcomas: optimization of retrieval technique and comparison to fresh tissue. AB - DNA content analysis of formalin fixed paraffin embedded (FFPE) tissue permits determination of the influence of DNA content on the prognosis in cohorts of patients for whom the clinical outcome is known. Of key importance in such an analysis is the accuracy of DNA content determination. Variations in the quality of DNA histograms from FFPE tissues of different types prompted a comparative evaluation of the preparative methodology of FFPE soft tissue sarcomas for DNA flow cytometry. Following deparaffination and rehydration of fixed tissue, and prior to fluorochrome staining, tissue blocks of 15 DNA aneuploid soft tissue sarcomas were subjected to repeated experimental (time x concentration) enzyme exposures. The goal of these studies was to define the optimal tissue specific retrieval technique with the coefficient of variation, maintenance of DNA aneuploidy, and DNA index as endpoints. After optimizing the technique, the DNA content of 50 soft tissue neoplasms derived from FFPE specimens was compared to the corresponding fresh surgical tissue. The observed 14 percent error rate in the determination of DNA ploidy status suggest limited utility for FFPE tissue in prospective therapeutic trials of soft tissue sarcoma. PMID- 8472610 TI - Flow cytometric analysis of xenobiotic metabolism activity in isolated rat hepatocytes. AB - Flow cytometry offers great potential for the study of xenobiotic metabolism in intact cells. We explored this application by the use of ethoxyfluorescein ethyl ester (EFEE) and isolated rat hepatocytes, a classic system for studying such reactions. EFEE is only weakly fluorescent and it diffuses freely into viable cells, where it is metabolized to fluorescein by a process dependent upon mixed function oxidase activity. In the current study, viable hepatocytes were first identified by flow cytometric assessment of fluorescein diacetate staining. The viable subpopulation was also identifiable on the basis of forward and right angle light scattering properties alone, and it was in this fraction that EFEE metabolism was measured. Metabolism of EFEE to fluorescein was quantified by flow cytometry. SKF 525A, alpha-naphthoflavone, and metyrapone, classic inhibitors of mixed-function oxidation, each inhibited the metabolism of EFEE. These results demonstrate the potential of EFEE for use in flow cytometric studies of drug metabolism, such as in multiparameter mechanistic assays of cellular xenobiotic metabolism and toxicity, and in the isolation by fluorescence-activated cell sorting of subpopulations which differ in this activity. PMID- 8472611 TI - Flow cytometric estimation of poly(A)+ RNA by fluorescent in situ hybridization. AB - A method for the detection of poly(A)+ RNA in cell suspensions by in situ hybridization and flow cytometry is described. The hybridizing properties of oligothymidylate o(dT) was well preserved after coupling to fluorescein. This fluorescent oligonucleotide was used as a probe to determine the poly(A)+ RNA content of fixed HL60 leukemic cells by flow cytometry. Labeling was considerably reduced by treating the cells with RNAse, and by competitive hybridization with either poly(U) or free poly(A). Labeling was also decreased in a time-dependent fashion by incubating the cells with actinomycin D prior to fixation. This method represents an improvement on the methods measuring total RNA and could be of value in investigations on the effect of drugs on RNA metabolism. PMID- 8472612 TI - Flow cytometric evaluation of human basophils. AB - The expression of CD45 and IgE cell surface antigens on human leucocytes was studied by flow cytometry. More than 80% of sorted cells that expressed low CD45 (CD45dim) and high IgE (IgEbright) antigen site density were identified as basophils. Immunomagnetic depletion of the CD45dim-IgEbright cell subset by a biotin-coupled anti-IgE antibody and streptavidin-coated magnetic beads was greater than 90%, and more than 80% of cells binding significant numbers of beads exhibited the morphological characteristics of basophils. Interestingly, when the cell staining was performed in the presence of calcium and magnesium, we observed a significant increase of CD45 and an equivalent decrease of IgE cell surface expression, as well as an IgE concentration dependent diminution of the number of CD45dim-IgEbright cells. PMID- 8472613 TI - Identification of a marker chromosome in a rat ascitic tumor by flow cytometry using a modified method for preparing chromosome suspensions. AB - Preparation of good chromosome suspensions is a crucial step in obtaining good flow karyotypes from different types of cells. Although several methods are in use, not all are suitable for all cell types. Primary cells from murine tissues are specially difficult to flow karyotype. We have modified the existing protocols for preparing chromosome suspensions from the Zajdela ascitic hepatoma (ZAH) cells of rat and have constructed their flow karyograms. Our karyograms show a distinct marker chromosome in these cells, which could not be resolved using other protocols. We have also used this method for preparing chromosomes from the bone marrow cells of the rat and have compared their flow karyograms with the ZAH karyotype. We expect that our protocol will be useful for studying other types of tumor and normal cells. PMID- 8472614 TI - Chronic hepatitis. AB - Evaluation, management and treatment of patients with chronic inflammation of the liver is an important task for the clinician. Almost every ongoing liver injury has an element of inflammation. In those disorders grouped as chronic hepatitis, the brunt of the liver injury is borne by the hepatocyte and continues until either the stimulus is removed or the inflammatory response is blunted. Chronic viral infection is by far the most important cause of chronic hepatitis. Hepatitis B and hepatitis C infections are both frequent causes and may result in cirrhosis. Interferon therapy has proven useful in the treatment of some patients with bone disorders. Idiopathic autoimmune chronic hepatitis is an important contributor to the diagnosis of chronic hepatitis and usually responds to corticosteroid therapy. Because of the availability of effective therapy, Wilson's disease, which is a quite rare but important cause of chronic hepatitis, should be considered. Even more rarely, an ongoing reaction to the continued administration of a therapeutic drug leads to chronic hepatitis. Advances in diagnosis, increased understanding of the courses followed by each of the major disorders, and the availability of effective treatment for many patients has heightened interest in the syndrome of chronic hepatitis. PMID- 8472615 TI - Acute mesenteric ischemia: pathophysiology, diagnosis, and treatment. AB - Ischemia has traditionally been viewed as arising only from abnormalities of oxygen dynamics, namely the cellular hypoxia resulting from the imbalances between oxygen supply, consumption, and demand. Recently, it has become clear that such a view is too restrictive. Hypoperfusion may be caused by both anatomic and functional impediments to either inflow or to outflow from an organ. Furthermore, the pathophysiologic consequences are likely to involve not only cellular hypoxia, but also a restricted supply of nutrients and other important molecules and an abnormal elimination of physiologic wastes such as carbon dioxide. Hence the recommendation that ischemia be defined as a dual defect of oxygen deficit and carbon dioxide excess. AMI is, therefore, a severe anatomic or functional impediment to the splanchnic circulation, resulting in a dual defect of intestinal hypoxia and cellular hypercarbia. Although the functional and structural consequences of cellular hypoxia are well known, the pathophysiology of cellular hypercarbia has only begun to be explored. AMI syndromes include three related processes: occlusive mesenteric ischemia, nonocclusive ischemia, and sepsis-induced SI. Leakage of bacteria or bacterial toxins into the circulation during mesenteric ischemia forms the basis of the systemic components of this syndrome. Striving for an earlier diagnosis, treating the systemic (septic) consequences, and taking measures to promptly restore mucosal oxygen balance through aggressive pharmacologic and appropriate surgical intervention have significantly improved the prognosis. About 80% of patients with acute arterial embolism, 60% of those with nonocclusive ischemia, and only 20% of patients with arterial thrombosis are expected to live without significant residual nutritional deficits. The cause of death is usually sepsis and multisystem organ failure, and therefore, further reductions in mortality are likely to occur with the improved prevention and treatment of sepsis. PMID- 8472616 TI - Association of elastin glycation and calcium deposit in diabetic rat aorta. AB - The relationship between glycation of the aortic elastin and calcium deposits in the aorta was studied in streptozocin (STZ)-induced diabetic rats. 5 Hydroxymethylfurfural (5-HMF) which was released from aortic elastin by acid, was assayed after STZ treatment as an index of early stage glycation. The amount of released 5-HMF increased at 5 weeks and paradoxically decreased at 10 weeks after STZ treatment, though it remained higher than that of control rats. This paradoxical pattern was reproduced by the in vitro incubation of elastin with glucose and it is presumably due to further advancement of glycation reactions in diabetic rats. The level of 5-HMF did not change significantly in control rats at corresponding time points of 9, 11 and 16 weeks of age. Fluorescence of porcine pancreatic elastase I-digested elastin which served as an index of advanced glycation, increased by 1.6 times at 3 weeks and reached a maximum of 1.9-fold higher than that of control rats at 10 weeks. The calcium content of the aorta at 10 weeks in diabetic rats was significantly increased by 1.4-fold compared with control rats. This study showed that the increased elastin glycation in the aorta even at the early stage of diabetes is associated with calcium deposit in the aorta. These results are consistent with the interpretation that elastin glycation in the aorta is the potential accelerating factor for diabetic macroangiopathy. PMID- 8472617 TI - Aminoguanidine inhibits protein browning without extensive Amadori carbonyl blocking. AB - It has been proposed that aminoguanidine reacts extensively with Amadori carbonyl groups of glycated proteins thus blocking them and inhibiting the further reactions which lead to browning and fluorescence development. We have glycated bovine serum albumin in the presence of 1, 5, 10 and 25 mM aminoguanidine and measured fluorescence development at 440 nm upon excitation at 370 nm, free (unblocked) Amadori groups as fructosamine with a colorimetric assay and furosine by HPLC, as an index of total Amadori products. Aminoguandine significantly inhibited fluorescence development at all the tested concentrations (31%, 65%, 69% and 82% inhibitions, respectively) (P < 0.001). Blocking of Amadori groups was demonstrated by decreased fructosamine and unchanged furosine yields but only at the higher concentrations and to a very limited extent (13% and 27% blocking, respectively) (P < 0.01). Incubation of Aminoguanidine with albumin produced the appearance of 320 nm absorbing yellow chromophores, quite increased in the presence of glucose. These results suggest that Aminoguanidine is able to block Amadori groups, as previously hypothesized, but question the importance of this mechanism as an explanation of its capacity to inhibit browning. Scavenging of glucose seems to have no impact on glycation as seen by unchanged furosine yields. PMID- 8472618 TI - Assessment of pupillary responses to light with IRIS. AB - With a newly developed method, IRIS, the potential usefulness of various parameters of pupillary reflexes for the assessment of autonomic nerve function was studied. Constriction latency decreased and dilatation latency increased significantly with higher intensities of light (P < 0.01 and P < 0.05, respectively). Thirteen subjects were tested twice one year apart in order to examine long-term intra-individual variability; no significant differences (all P > 0.3) were found. Reproducibility and reliability of hippus and pupil cycle time were lower than for the determination of constriction and dilatation latency. None of the parameters was correlated with age (all P > 0.3). We conclude that pupillary constriction and dilatation latency, assessed with IRIS, are the main dynamical parameters for the study of parasympathetic and sympathetic parts of the autonomic nervous system, that controls the pupillary system. Although a statical parameter, useful additional information may be obtained from the dark adapted pupil diameter. Hippus cycle time and pupil cycle time do not provide additional information and therefore cannot be recommended as standard tests for autonomic nerve function. PMID- 8472619 TI - The inhibitory action of buformin, a biguanide on gluconeogenesis from alanine and its transport system in rat livers. AB - The effect of buformin, a biguanide, on gluconeogenesis from 10 mM alanine in the presence of 143 nM glucagon were studied using isolated rat liver perfusions. In addition, to investigate possible mechanisms of biguanide action, alanine utilization in isolated rat liver perfusion and [3H]alanine uptake in isolated hepatocytes were observed. Buformin (1.85 mM) strongly inhibited gluconeogenesis from alanine in the presence of glucagon in both normal and streptozocin-induced diabetic rat livers. This inhibition was followed by a decrease in alanine utilization. Both of these inhibitory effects of buformin were dose-dependent. [3H]Alanine uptake was significantly inhibited by buformin. The effect of this agent was similar to but weaker than that of ouabain. However, tolbutamide failed to reduce either alanine utilization or [3H]alanine uptake, although this drug significantly inhibited gluconeogenesis from alanine. These data suggest that biguanides may reduce hepatic alanine utilization via the inhibition of Na+/L alanine transport activity as one possible mechanism, resulting the inhibition of gluconeogenesis from alanine in the presence of glucagon. PMID- 8472620 TI - Factors influencing the clinical outcome of continuous subcutaneous insulin infusion in routine practice. AB - Possible factors that might influence the outcome of continuous subcutaneous insulin infusion (CSII) treatment were investigated in forty-nine, type 1, diabetic patients with median treatment of 3.25 years in routine diabetes care. In nine patients pump treatment was discontinued largely within the first 6 months. Patients characterized as blue-collar workers discontinued pump treatment at a significantly higher rate. Of the remaining forty patients those with the longest treatment experience were of attracted interest. Among twenty patients who had used CSII three years or more improvement of metabolic control was most evident in patients with high haemoglobin A1c (HbA1c) values before CSII (R square 0.673, P = 0.0001) and in subjects with low insulin requirements on injection therapy (R-square 0.334, P = 0.0076). This improvement was not explained by more frequent monitoring of blood glucose only. It was found that those who had the lowest body mass index (BMI) before pump treatment had the more pronounced increase of BMI, while those in the upper normal range had an unchanged or reduced body mass (R-square 0.271, P = 0.0115). We conclude that high HbA1c values, low insulin requirements and low body mass in conventional injection therapy are the most important factors when trying to achieve and maintain metabolic improvement in CSII treated type 1 diabetic patients. PMID- 8472621 TI - A study of response pattern of non-insulin dependent diabetics to yoga therapy. AB - Changes in blood glucose and glucose tolerance by oral glucose tolerance test (OGTT) after 40 days of yoga therapy in 149 non-insulin-dependent diabetics (NIDDM) were investigated. The response to yoga in these subjects was categorized according to a severity scale index (SSI) based on area index total (AIT) under OGTT curve. One hundred and four patients showed a fair to good response to the yoga therapy. There was a significant reduction in hyperglycemia and AIT with decrease in oral hypoglycemia and AIT with decrease in oral hypoglycemic drugs required for maintenance of normoglycemia. It is concluded that yoga, a simple and economical therapy, may be considered a beneficial adjuvant for NIDDM patients. PMID- 8472622 TI - Estimation of the prevalence of diabetes mellitus diagnosed, and incidence of type 1 (insulin-dependent) diabetes mellitus in the Avila Health Care region of Spain. AB - We studied the prevalence of diabetes mellitus diagnosed in the Avila Health Care region, Spain, based on the prescribed daily dosage (PDD) of insulin (corrected in function of insulin loss (PDDc)) and sulphonureas, from a sample representative of prescribing physicians (A, n = 48) and pharmacies (B, n = 25) in our region. The amounts of the PDDcs of insulin sold during 1989 per 1000 inhabitants/day were 6.06 and 6.20, respectively for the two samples (A and B). The figures for PDDs of sulphonurea/1000 inhabitants/day were 16.25 and 19.16, respectively. We determined the proportion that diabetic patients on diet alone represented in relation to non-insulin treated diabetic patients who visited the only specialized clinic for diabetic patients in our province in 1989. These patients accounted for 40.83% of non-insulin treated diabetic patients. The patients being treated with biguanides or with a combination of anti-diabetic drugs accounted for less than 1% of those treated in the specialized clinic. Taking this into account, the prevalence of diabetes mellitus in Avila was 3.35% (C.I. 95%: 3.10-3.59), according to the sample A and 3.85% (C.I. 95%: 3.50-4.31) according to the sample B. In addition, we studied the hospital admission records during three consecutive years in order to find out the incidence of type 1 insulin-dependent diabetes mellitus (IDDM) below 15 years of age in the Avila Health Care region of Spain. All prescribing physicians that did not work in the Hospital (197 in the rural area and 18 in the urban area) were used as the secondary source for validation of case ascertainment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472624 TI - Gangliosides prevent insulitis but not islet B cell destruction in low-dose streptozocin-treated mice. AB - High doses of gangliosides were given to low-dose streptozocin(LDS)-treated mice, in order to observe their ability to prevent diabetes in this animal model and also to look for any modification in the early histopathological lesions occurring in pancreatic islets. Cronassial, 150 mg/kg body wt., (21% GM1, 40% GD1a, 16% GD1b, 19% GT1b and 5% other) was given to 20 C57BL6/J mice in which diabetes was induced 1 week after the start of the Cronassial treatment. Data obtained from animals killed 1 and 3 weeks from the end of the LDS treatment demonstrate that gangliosides stop infiltration of the islets but do not prevent destruction of islet B cells. Therefore, inflammation is not obligatory for the development of the disease in this model. Streptozocin exerts a direct cytotoxic action of considerable importance and is able to act prolongedly on target cells. The destruction achieved is similar to that produced by administration of a single high dose even though it takes place over a longer period. Our results underline the complexity of the LDS-induced diabetic disease. PMID- 8472623 TI - Immunological resistance to human biosynthetic insulin--effects of immunosuppression and plasmapheresis. AB - A 55-year-old gentleman, after being treated for a short time with a diet and with Chlorpropamide, was switched to purified porcine insulin due to ketonuria and ketoacidosis. After a year the patient developed immunological insulin resistance (mean daily insulin dose: 3.72 U/kg body weight; anti-insulin antibodies 78%). In order to lower anti-insulin antibodies human recombinant DNA insulin was introduced into further therapy. Contrary to expectations, the patient did not reduce whatsoever his anti-insulin antibodies and his daily insulin dose increased up to 5.63 U/kg body weight. Introduction of combined immunosuppressive therapy (prednisone plus azathioprine) together with plasmapheresis resulted in rapid lowering of daily insulin requirement and reduction in anti-insulin antibodies. Immunosuppressive therapy was continued with 10 mg of prednisone and a year later the patients insulin daily requirement was 0.66 U/kg BW while his antibodies were 18%. The possible causes of insulin resistance to human recombinant DNA insulin are discussed as well as the advantage of combined immunosuppressive therapy together with plasmapheresis that was used for rapid lowering of insulin daily requirement and anti-insulin antibodies titer. PMID- 8472625 TI - The effects of subcutaneous human proinsulin on the production of 64/65 split proinsulin, glucose turnover and intermediary metabolism in non-insulin-dependent diabetic man. AB - We have compared the effects of subcutaneously injected human proinsulin, insulin zinc suspension and inactive diluent (control) on glucose turnover, intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetic man. Six weight-matched (24.8 +/- 1.6 kg M-2) non-insulin-dependent diabetic subjects underwent 3 separate, randomized, 10 h isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6'6'2H2] glucose. Each subject received 0.35 U/kg of hormone or control made up to isovolumetric amounts. The mean blood glucose level of 7.3 +/- 0.8 mmol/l was similar at the start of each isoglycemic clamp. Incremental area under the curve proinsulin levels (1195 +/- 146 nmol/l) were about 21-fold higher, on a molar basis, than insulin (62.4 +/- 10 nmol/l). Des 64/65 split proinsulin increased in a parallel manner to intact proinsulin (r = 0.99, P < 0.0001) and comprised approximately 13% of the intact proinsulin concentration. Hepatic glucose production was suppressed similarly following proinsulin and insulin zinc injection. However, both proinsulin and insulin zinc had a significantly greater effect on suppression of hepatic glucose production compared to control (P = 0.01, P = 0.009, respectively). Metabolic clearance rate of glucose fell significantly during the control studies compared to insulin zinc or proinsulin injections (P < 0.05). Blood lactate, pyruvate and alanine concentrations were similar following control or hormone injections. However blood glycerol, 3-hydroxybutyrate and plasma-non-esterified fatty acids were suppressed significantly by proinsulin and insulin zinc compared to control injections. The conclusions were: (1) In overnight fasted hyperglycemic non insulin-dependent subjects s.c. injections of proinsulin and insulin zinc can produce similar effects on glucose turnover, intermediary lipid and carbohydrate metabolism. (2) Similar carbohydrate intermediary metabolism profiles can be obtained following insulin zinc, proinsulin or control injections. (3) However lipolysis and ketogenesis were significantly suppressed by both hormones compared to control. (4) Subcutaneous proinsulin injection resulted in approximately 13% conversion to des 64/65 split proinsulin. PMID- 8472626 TI - Coexistence of diabetes and hypertension results in unique structural alterations in the renal artery in rats beyond that found with diabetes alone. AB - Numerous investigators have presented evidence of increased mortality in patients with diabetes mellitus due to cardiovascular disease. It is still unclear as to the reasons why there is a predisposition to vascular pathology that in the advanced state leads to atherosclerosis. Our hypotheses were: (1) The condition of diabetes mellitus in a streptozocin animal model may show vascular changes similar to early pathology in macrovessels and (2) since the model is normotensive, inducing hypertension will result in early atherogenic pathology. We carried out a quantitative analysis of the renal artery using light and electron microscopy to test the hypotheses. Male Wistar rats had diabetes mellitus induced using streptozocin and 1 week later half of the diabetic animals had hypertension induced with deoxycorticosterone acetate (DOCA). Samples were taken following 7 weeks of diabetes, or 7 weeks of diabetes with DOCA administration during the final 6 weeks. The renal artery from the diabetic group did not have any differences in wall or luminal dimensions from control, but did have proportionately more extracellular matrix than smooth muscle in the tunica media. This is evidence of structural change, in a large supply artery, as a manifestation of diabetes mellitus, similar to that seen in vascular disease. Vessels from the control/hypertensive had a significantly thickened tunica media as did the diabetic/hypertensive over control values. The latter also had proportionately even greater significant elevation of the extracellular matrix compared with either the diabetic or control/hypertensive. In addition, only the diabetic/hypertensive group showed marked subendothelial invasion of macrophage type cells and deposits of various shapes and densities. We have, therefore, demonstrated significant vascular alteration due to the diabetic condition in this animal models and also shown that with hypertension and diabetes combined, the early vascular pathology is exacerbated. PMID- 8472627 TI - Mechanism of insulin secretion by midaglizole. AB - Midaglizole was introduced as a hypoglycemic agent, but its insulin releasing mechanism remains unknown. In the present study, the effect of midaglizole upon the B cell function of the pancreas was investigated, using an in situ local circulation of the canine pancreas. The graded doses of midaglizole (0.2, 1.0 and 2.0 mg/kg) revealed a dose-related response of plasma insulin. The administration of yohimbine, a classical alpha 2-antagonist (1.11 mg/kg) revealed a similar increase in plasma insulin to that with midaglizole of equimolar amount. During the clonidine infusion midaglizole did not elicit any significant rise in plasma insulin, whereas yohimbine increased plasma insulin significantly. During glucagon infusion plasma insulin increased following midaglizole infusion but not by yohimbine. The simultaneous administration of diazoxide (K-channel opener) suppressed the midaglizole-induced insulin secretion. These results obtained in the present experiments revealed a different mechanism of insulin releasing action of midaglizole from that of yohimbine. Furthermore, the finding with diazoxide administration suggests that midaglizole stimulates insulin release through an interaction of K(+)-channel of the pancreatic B-cell. PMID- 8472628 TI - Clinical evaluation of biosynthetic glucagon treatment for recovery from hypoglycemia developed in diabetic patients. The GL-G Hypoglycemia Study Group. AB - Biosynthetic glucagon (GL-G) produced by recombinant DNA technology with transformed yeast strains is already available for clinical use. We studied the effects of 1 mg GL-G injection on plasma glucose level and hypoglycemic symptoms in 38 diabetic patients treated with insulin or oral hypoglycemic agents during spontaneous hypoglycemic episodes. In both intramuscularly and intravenously administered GL-G groups, plasma glucose significantly increased from 58.1 +/- 11.4 to 113.2 +/- 6.9 mg/dl (i.m., n = 17, P < 0.01) and from 76.4 +/- 4.4 to 125.7 +/- 5.9 mg/dl (i.v., n = 15, P < 0.01), respectively 20 min after the administration and the symptoms due to hypoglycemia subsided promptly after the injection of GL-G in 27 cases. The hyperglycemic effect of intramuscularly injected GL-G was more potent and long-standing than when intravenously injected, particularly in insulin-dependent diabetic (IDDM) patients. Neither significant changes of antibody levels against yeast proteins nor serious adverse effects were observed after GL-G administration. Biosynthetic glucagon is safe and useful for the treatment of hypoglycemia developing in diabetic patients. PMID- 8472629 TI - Self-reported quality of life and the effect of different clinical and demographic characteristics in people with type 1 diabetes. AB - The aims of the present study were to describe how people with type 1 diabetes experienced their quality of life and to examine the effect of the different background characteristics of sex, age, social status, education, disease duration. HbA1 levels, regimen and the frequency of complications on self reported quality of life. A self-administered questionnaire consisting of 28 items measuring satisfaction within the physical, psychological, social and activity/behavioural life-domain and 11 well-being scales was completed by 247 patients with type 1 diabetes who consecutively attended a Norwegian diabetes clinic. Main findings from the study showed that over 80% of patients reported their capacity for self-care, general well-being, satisfaction with life and social contacts to be quite good or better. Forty five percent of patients perceived their life situation to be negatively effected due to diabetes. Multivariate analysis showed that living alone had a negative effect on satisfaction in the physical, social and psychological life-domain. Higher levels of HbA1 were associated with reported lower satisfaction within the physical and activity/behavioural life-domain. The effect of the different background characteristics on reported well-being showed no consistent pattern. These findings indicate that the majority of patients in this study experienced a satisfactory quality of life despite living with a chronic illness such as diabetes. PMID- 8472630 TI - Immunoprotection in spontaneous remission of type 1 diabetes: long-term follow-up results. AB - This prospective pilot study was undertaken to test the efficacy of oral methyl prednisolone (MP) therapy at spontaneous remission phase of type 1 diabetes in intervening the course of the disease. Twenty-five type 1 diabetic patients who were classified as having a spontaneous remission (honeymoon) were divided into treatment and non-treatment groups on voluntary basis. Fifteen patients thus making up the treatment group (13 males and 2 females, mean age 23.8 +/- 6.2 years) received 0.7-1.0 mg/kg/day of MP p.o. for 2 weeks. The dose of the drug was then gradually diminished every week until 5 mg/day (approx. 0.1 mg/kg/day) and discontinued at 10 +/- 2 weeks. In case of hyperglycemia occurring in 12 of 15 patients due to the administration of steroid, insulin was used to normalize blood glucose levels (average 0.47 +/- 0.21 IU/kg/day). The non-treatment group (8 males and 2 females, mean age 21.8 +/- 8.9) did not receive any special medication or placebo except for insulin whenever necessary to regulate glycemia. Upon completion of protocol, all patients in treatment group displayed clinical remission with 10 still in non-insulin requiring remission for follow-up periods ranging between 16 and 91 months. The remaining 5 patients relapsed within 3-15 months of therapy. Other metabolic (including basal and stimulated C-peptide levels) and immunological indices that have spontaneously ameliorated with the occurrence of honeymoon were also maintained within normal range in the NIR patients. Meanwhile, natural remission in the non-MP-treated group terminated at 3.4 +/- 0.6 months with deterioration of all metabolic and immunological markers as well as increasing requirements for insulin. In conclusion, the spontaneous remission of the patients could be prolonged significantly by MP therapy as opposed to no therapy (P < 0.001). These results suggest that the spontaneous remission phase may be a crucial point of intervention in immunotherapy of type 1 diabetes and that randomized trials with MP at this particular phase would be worthwhile. PMID- 8472631 TI - The effects of participation in a support group on self-assessed quality of life in people with insulin-dependent diabetes mellitus. AB - The aim of the present study was to examine the effect of participation in a support group on self-assessed quality of life. Based on an initial self-report assessment of quality of life 25 people were allocated to 5 groups comprising 4-6 participants (intervention group) and 36 controls. The support groups met fort nightly for 6 months and were facilitated by the investigator and a diabetic nurse specialist. Group processes were aimed at alleviating distress and improve satisfaction with life and included installation of hope, imparting information and group cohesiveness. Both the intervention and control group completed the quality of life measure at the end of 6 months. There were no significant differences between the intervention and control group on background characteristics or quality of life pre-test scores. No significant differences were found between the intervention and control group on difference in pre and post-test scores, indicating that support group participation did not effect self assessed quality of life. This finding may be due to methodological issues i.e. selection, sample size and the instrument used, the implementation of the intervention and/or the concept of quality of life as an outcome variable. PMID- 8472632 TI - Conflicting gastric inhibitory polypeptide data: possible causes. AB - The literature with respect to GIP is flooded with conflicting data especially with respect to its role in type 2 diabetes mellitus, obesity, type 1 diabetes mellitus and chronic pancreatitis. This review describes possible reasons for the discrepancies which include species variation of GIP, heterogeneity of molecules with different immunoreactivity and bioactivity, deterioration of immunoreactivity of standard and sample on prolonged storage and the effect of the preceding intake of type and quantity of food. The problems can be resolved by raising antibodies to synthetic human GIP and its fragments, the chemical characterization of and the raising of antibodies to immunoreactive GIP 8000, the correct storage of samples and the standard preparation of subjects prior to experimental procedures. PMID- 8472633 TI - [Radiofrequency ablation of accessory pathways in pre-excitation syndrome]. AB - Various parameters relating to the radio-frequency ablation of accessory pathways were studied in 53 patients (27 males, 26 females: mean age 38.5 [14-64] years) with a history of paroxysmal tachycardia (over 1 month to 50 years), shown to be caused by an accessory pathway (Wolff-Parkinson-White syndrome). In all patients the following values were obtained: (1) number of procedures necessary to achieve permanent blockage of the accessory pathway (1-4); (2) duration of each procedure (45-420 min); (3) duration of fluoroscopy (5-102 min); (4) number of necessary radio-frequency applications (1-48); and (5) cumulative energy per procedure. To ablate left-lateral pathways (n = 10) required fewer procedures, shorter duration per procedure, shorter fluoroscopy time, fewer current applications and less total energy than coagulation of right-sided pathways (n = 10). Those various parameters were greatest for ablation of septal and para-septal pathways (n = 9). Pathways which conducted only retrogradely (n = 15) were more difficult to ablate than those with anterograde conduction (n = 38). There were two complications. In one case a tension pneumothorax occurred after faulty puncture of the subclavian vein; in the other, the left ventricle was perforated causing an acute tamponade which required pericardiocentesis with subsequent suture closure of the perforation. It is concluded that, in principle, all accessory pathways, regardless of their conduction potential and site, can be ablated by a radio frequency current. PMID- 8472634 TI - [Improvement of coronary reserve following regression of hypertrophy resulting from blood pressure lowering therapy with a beta-receptor blocker]. AB - The coronary microcirculation was investigated by the argon gas method in ten patients (eight men, two women; mean age 56 [44-63] years) before and after an average of 12.9 (9-18) months of treatment with the cardioselective beta-receptor blocker bisoprolol. Left ventricular muscle mass was measured echocardiographically, before and after the treatment. All these patients were known to have hypertension, with exercise-related angina and ischaemic signs in the resting ECG, but normal coronary angiograms. After the treatment period both maximal coronary perfusion and coronary reserve had increased by 22%. At the same time, left ventricular muscle mass had decreased from 161 +/- 18 to 146 +/- 21 g/m2. These results demonstrate that blood pressure reducing treatment can bring about not only a regression of left ventricular hypertrophy, but also an improvement in coronary reserve. PMID- 8472635 TI - [Abdominal aortitis in polymyalgia rheumatica. Disease course as documented with computerized tomography and proton spin tomography]. AB - In a 59-year-old woman, after four years of ambiguous and unidentified course of her disease (feeling of weakness, inappetence, weight loss, pain in the shoulder girdle, sub-febrile temperatures, increased BSR), polymyalgia rheumatica was eventually diagnosed. The findings at the abdominal aorta were particularly marked: sonography revealed a 10 mm wide echo-poor fringe around the aorta which in the computed tomogram became slightly more echogenic after injection of contrast medium. In the magnetic resonance tomogram (MR) the aortic wall was homogeneously thickened and well-defined against the retroperitoneal tissue. Subsequent to the diagnosis a therapy with glucocorticoids was initiated and strictly continued for by now 18 months. This resulted in long-term clinical remission. CT and MR proved highly suitable for long-term monitoring (> 5 years). PMID- 8472636 TI - [Diagnostic advantage of biplane trans-esophageal echocardiography]. PMID- 8472637 TI - [Isolated systolic hypertension in old age]. PMID- 8472638 TI - [Exceeding of speed limit by physicians responding to emergencies. Decision by the Bavarian Supreme Assize Court on 10-1-1990]. PMID- 8472639 TI - [Colonoscopy using contrast media]. PMID- 8472640 TI - [Epidemiologic studies of C. bovis and T. saginata infections in eastern and western Germany]. AB - An investigation on the epidemiological situation of cysticercosis/taeniasis (Taenia saginata--GOEZE, 1782) showed clear differences in the proportion of cattle infected with C. bovis in the eastern and western part of Germany. Reasons for the high level of the C. bovis infection in the former GDR are a bad waste water situation and an increased intensification of agriculture (high concentration of cattle, increased irrigation). PMID- 8472641 TI - [Trace element supply of newborn calves. Effect of the mother and of the genetic makeup, sex and degree of maturity of the newborn]. AB - Stillborn calves of a large dairy cattle herd were used for investigations of trace element (Fe, Zn, Cu, Mn) content of the liver and heart muscle. Trace element content varied markedly in the liver and in the heart muscle too but in the heart muscle with a smaller degree. Calves from heifers had a greater trace element content in the liver and heart muscle than those from cows. Premature calves had small amounts of Mn and Cu in their livers and small but term calves had less Fe and Zn in their livers. Single calves from cows had a greater amount of trace elements in the liver and heart muscle than twin calves. PMID- 8472642 TI - Liquid storage and freezing of semen from New Forest and Welsh Pony stallions. AB - Two experiments were conducted to examine the effects of liquid storage extender and of a modified freezing protocol on motility and morphology parameters of 3 year-old pony stallions. In experiment 1 ejaculates were diluted 1 + 1 (v+v) with glycine-egg-yolk extender (D11) or skim milk extender (SME), centrifuged, resuspended in the corresponding extender and kept at +5 degrees C. Concerning motion characteristics, both progressive motility and average path velocity of semen stored in SME was significantly superior to semen stored in D11 after 6, 18 and 42 hrs. However, over time of storage the D11 seemed to have more beneficial effect on sperm morphology and acrosome integrity compared to SME. In experiment 2 ejaculates--after centrifugation in D11--were resuspended in lactose-egg-yolk glycerol extender, packaged in 0.5 ml straws and frozen at computer controlled cooling rates. There was a significant decrease from fresh to post thaw motility, velocity and percentage of morphologically normal spermatozoa, whereas acrosome morphology not seemed to be affected by freezing/thawing. PMID- 8472643 TI - [Basic reproductive toxicological studies of the effect of furazolidone on the hypothalamo-hypophyseo-gonadal axis of male rats]. AB - The reproductive-toxic effects of furazolidone on testis, epididymis and selected nuclei of the hypothalamus of male wistar rats were investigated. After a dosage of 50 mg/kg b.w. daily over five days no changes of testis and epididymis were detected in relation to controls by means of light microscope. Using morphometric methods a significant increase of the nucleus volume of the measured nuclei of the hypothalamus (Ncl. ventromedialis, Ncl. praeopticus medialis, Ncl. infundibularis) could be shown. After the high dosage of 200 mg/kg b.w. daily for five days testis and epididymis showed marked signs of atrophy and the volume of the investigated nuclei of the hypothalamus was significantly increased. These results suggest that--contrary to the wide spread opinion the testis would react most sensitive to chemical agents--more attention should be directed to the hypothalamus in reproductive-toxicological studies. PMID- 8472644 TI - [Testing of rapeseed with different glucosinolate contents in growing swine--a contribution for the evaluation of native harmful substances in food]. AB - Glucosinolates are present in kale but also in rapeseed meal. Rapeseed meal diets with 0.2 to 8 g (0.5-19 mmol) glucosinolates/kg were tested with a total of 197 growing pigs. The iodine supply was different. In case of lacking iodine pigs consumed less of feed with rapeseed meal. The growth was strongly lowered. Clinical hypothyroidism had occurred. In the serum T4 was not detectable. The strongly enlarged thyroid contained only little iodine. The Zn status was impaired. The serum vitamin A concentration was increased and Cu has been accumulated in the liver. Giving iodine the glucosinolates were without any effect or the effects were weakened. In case of < 2 g glucosinolates/kg diet the feed intake was not impaired. 1 g glucosinolates/kg diet had not affected thyroid weight (reference range: 80-120 mg/kg body weight). However iodine dosage was above requirement. In people an estimated daily intake of 0.1 g glucosinolates may be a health risk only under iodine deficiency conditions. PMID- 8472645 TI - [Comparison of EBL cells and ELISA in the culture and serological diagnosis of rhinitis atrophicans in swine]. AB - Pasteurella multocida isolates from 271 nasal swabs of pigs were tested in EBL cell culture for toxin production. Mixed bacteria cultures of the same swabs were examined in the P. multocida toxin ELISA K462 (Dakopatts). In the ELISA 114 swabs reacted positive, whereas toxigenic P. multocida were detected by the EBL cell test in 86 swabs. In a neutralization test (SNT) combined with EBL cell culture and with the ELISA 111 sera were examined for P. multocida antitoxin. The toxin had to be more concentrated for the ELISA than for the cell culture; therefore the SNT with EBL cells was more sensitive. Whereas 101 sera had titres of 1:4 or higher in the cell culture, 68 of these sera were positive in the ELISA. PMID- 8472646 TI - Human studies do not support the methylation threshold hypothesis for the toxicity of inorganic arsenic. AB - Inorganic arsenic (In-As) is an established human carcinogen. Methylation to monomethylarsonate (MMA) and dimethylarsinate (DMA) is believed to be the detoxification mechanism for In-As. Urinary measurement of In-As, MMA, and DMA is considered a good biological marker of internal dose to In-As, since it excludes other ingested forms of arsenic which are much less toxic, and because urinary excretion is the main form of elimination of In-As. A methylation threshold hypothesis for In-As has been proposed, stating that after exposure to In-As reaches a certain level or threshold, methylation capacity begins to decline, thus increasing the toxic effects of In-As. We investigated the validity of this hypothesis by analyzing the data from studies which measured urinary In-As, MMA, and DMA in different populations, ranging from background to high occupational and environmental exposure groups. We also present data from our study of a highly exposed population in California. Our analysis focused on the proportion of urinary In-As remaining in the unmethylated form [In-As/(In-As + MMA + DMA)]. The results indicate that epidemiological and experimental human data do not support the methylation threshold hypothesis. On average, 20-25% In-As remains unmethylated regardless of the exposure level. The wide range of interindividual variability in methylation capacity found in some studies warrants further investigation. PMID- 8472647 TI - Ozone effect on respiratory syncytial virus infectivity and cytokine production by human alveolar macrophages. AB - This study was performed to evaluate the effect of ozone (O3) exposure at 1 ppm for 2 hr on the susceptibility/resistance of adult human alveolar macrophages (AM) to infection with respiratory syncytial virus (RSV) in vitro and on RSV induced cytokine production by the AM. AM were first exposed to O3 or to filtered air and then infected with RSV at multiplicities of infection (m.o.i.) of 0.1, 1.0, and 10. The percentage RSV-infected AM and the amount of infectious virus released by the cells were determined at Days 2 and 4 after infection. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) levels in the supernatants were determined on Day 2. No difference in the percentage infected AM or in the amount of infectious RSV produced was found between control and O3 exposed cultures. However, O3-exposed AM infected with RSV at m.o.i. 1 produced less IL-1 in response to RSV infection than control AM: 63.6 pg/ml compared with 98.5 pg/ml. No difference in IL-1 was seen with m.o.i. 10. IL-6 levels were also decreased, but only after infection with m.o.i. 0.1. At this level of infection 830 pg/ml was produced by control AM as compared to 468.2 pg/ml by O3-exposed AM. TNF production was unaffected by O3 at all multiplicities of infection. Statistical analysis of the O3 effect on AM cytokine production induced by the different multiplicities, however, revealed no significant effect of O3. Based on these observations it appears unlikely that O3 alters susceptibility of AM to infection with RSV, nor does O3 dramatically alter cytokine production in response to RSV since effects on IL-1 and IL-6 secretion were only found with the lowest levels of infection which induced cytokine release. PMID- 8472648 TI - Airborne endotoxin concentrations in various work areas within a cotton mill in Central America. AB - Gram-negative bacteria and their endotoxins have been shown to cause profound changes in the structure and function of mammalian lungs. Airborne exposures in humans have resulted in bronchoconstriction and symptoms of chest tightness and dyspnea. Cotton dust is often heavily contaminated and endotoxin has been postulated to be the agent in cotton dust which is responsible for the byssinosis syndrome. Previous studies of cotton dust have revealed variable amounts of contamination by bacterial endotoxin, with the variability determined in large part by botanical and climatic characteristics. We report here the results of an environmental study conducted in a cotton mill located in the tropics of Central America using locally grown cotton. Results indicate that airborne endotoxin was present in all yarn preparation and weaving areas and ranged from a low of 18 EU/m3 in weaving to a high of 3138 EU/m3 in opening areas. Airborne levels and the amount of endotoxin per nanogram of dust were not higher than values obtained in temperate climates. PMID- 8472649 TI - Occupational health issues in developing countries. PMID- 8472650 TI - Evaluation of brain function in acute carbon monoxide poisoning with multimodality evoked potentials. AB - The median nerve somatosensory evoked potentials (SEP), pattern reversal visual evoked potentials (VEP), and brain stem auditory evoked potentials (BAEP) were studied in 109 healthy adults and in 88 patients with acute carbon monoxide (CO) poisoning. The upper limits for normal values of peak and interpeak latencies of multimodalities of evoked potentials in the reference group were established by a stepwise multiple regression analysis. SEP changes selectively affecting N32 and N60 were found in 78.8% of patients. There was prolonged P100 latency of VEP in 58.2% of the cases examined. The prevalence of BAEP abnormalities in comatose patients (36%) was significantly higher than that (8.6%) in conscious patients. BAEP abnormalities were most frequently seen in comatose patients who had diminished brain stem reflexes (77.8%). It has been found that a consistent abnormality involving N20 and subsequent peaks in SEP, a remarkable prolongation of P100 latency in VEP, or a prolongation of III-V interpeak latency in BAEP as well as the reoccurrence of evoked potential abnormalities after initial recovery all indicate unfavorable outcomes in patients with acute CO poisoning. The multimodality evoked potentials have proved to be sensitive indicators in the evaluation of brain dysfunction and in the prediction of prognosis of acute CO poisoning and the development of delayed encephalopathy. PMID- 8472651 TI - A study on the neurobehavioral effects of occupational exposure to organic solvents in Korean workers. AB - In order to investigate the neurobehavioral effects in workers occupationally exposed to organic solvents in Korea using WHO neurobehavioral core test battery (NCTB), a cross-sectional study of 113 male car painters and printers and 81 controls was conducted. Among the seven tests of the NCTB, only four tests- simple reaction time, Santa Ana dexterity, digit symbol, and Benton visual retention tests--were administered to the subjects because of time limitations. Painters and printers were exposed mainly to toluene, xylenes, and methyl ethyl ketone and often to solvent mixtures. The range of the solvent exposure level was 0.10-2.29 of hygienic effect. Poorer performance of Benton visual retention in the exposed group when compared to the control group was found after controlling confounders. No exposure-dependent effect was found. Further investigation with a matched control group regarding confounding factors is required for conclusive results. PMID- 8472652 TI - Axonal sprouting of motor nerve in acrylamide-intoxicated rats with progressive weakness. AB - Quantitative morphologic studies on the motor axons in endplates of extensor digitorum longus muscle (EDL M) and soleus muscle, and on the myelinated fibers of the nerve to EDL M and other lower limb nerves were made on rats showing progressive weakness, intoxicated with acrylamide for 4 weeks (test), using silver staining. Terminal sproutings were significantly greater in frequencies in test compared with control in both muscles. In addition, morphologic changes in test consisted of a significant increase in the number of axon terminal branches and in the frequency of swellings of the preterminal, terminal, and ultraterminal axons and in an increase of myelinated fibers showing axonal degeneration in the nerve to EDL M. Such findings were in contrast with the previous report that cumulative doses of acrylamide inhibit sprouting of motor axons in endplates. PMID- 8472653 TI - Polyneuropathy due to ethylene oxide, propylene oxide, and butylene oxide. AB - Axonal neuropathy occurs due to occupational ethylene oxide (EtO) exposure. The experimental model of human EtO neuropathy was established. In addition, the neurotoxic effects of propylene oxide (PpO) and butylene oxide (BtO) were demonstrated in rats. Although no human neuropathy due to PpO or BtO is reported, both chemicals must be considered to be neurotoxic, based on this study. PMID- 8472654 TI - Significance of subclinical entrapment of nerves in lead neuropathy. AB - We examined a left-handed 25-year-old man engaged for 2 years at a vinyl chloride resin factory where he had been exposed to lead stearate, a stabilizer of resin. Neurological examination revealed atrophy of small hand muscles, especially in the left dorsal interossei. Sensation of all modalities was intact. A nerve conduction study showed conduction block at the elbow, indicating possible cubital tunnel syndrome. Following CaEDTA therapy, continued recovery of conduction velocities, amplitude of compound muscle action potential, and diminution of conduction block at elbow were observed within a few months. In lead intoxication, nerves may incur mechanical damage. Subclinical entrapment may thus be an important factor leading to vulnerability of nerves in lead neuropathy. PMID- 8472655 TI - Evaluation and control of mercury vapor exposure in the cell house of chlor alkali plants. AB - A pilot study was carried out in the cell houses of three chlor alkali plants to assess level of exposure to mercury vapors among workers by air and biological monitoring. Overall airborne mercury concentrations (mg/m3) were found to range from 0.05 to 0.42 (mean, 0.21, n = 68), 0.03 to 0.16 (mean, .08, n = 49), and 0.02 to 0.17 (mean, 0.04, n = 26), whereas urinary mercury levels (mg/liter) of the exposed workers of the respective plants ranged from 0.076 to 0.592 (mean, 0.207, SD, 0.107, n = 19), 0.015 to 0.220 (mean, 0.070, SD, 0.054, n = 16), and 0.013 to 0.275 (mean, 0.06, SD, 0.054, n = 23). Unattended mercury spillage on the floor and improper sealing of the lids of the end boxes of electrolysis cells were found to be main factors attributing to prevalence of mercury vapors in excess of the permissible exposure limit of 0.05 mg/m3. Based on the deficiencies observed, appropriate control measures have been suggested to reduce airborne mercury vapor concentrations in the work environment. PMID- 8472656 TI - Studies on neurolathyrism. AB - Neurolathyrism is a neurological condition seen among people who eat the seeds of Lathyrus sativus (LS) as a principal source of food energy for 2 months or more. It is characterized by severe muscular rigidity and paralysis of the lower limbs. beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid is the principal toxin found in the seed. No experimental animal model for neurolathyrism could be produced by feeding either the seeds or the toxin, although the condition has been known for centuries. We discovered that experimental neurolathyrism could be produced in guinea pigs and primates that needed an external supply of ascorbic acid by making them subclinically deficient in ascorbic acid and feeding them the seeds of LS or extracts thereof. Autoclaving the seeds of LS with lime removes the toxin. PMID- 8472657 TI - Neurobehavioral effects in occupational chemical exposure. AB - Neurobehavioral effects in 30 female workers (aged 18-41, mean 25.6) exposed to an average of 341 mg/m3 (SD 100) toluene for an average of 5.7 years (SD 3.3) compared with 30 matched controls (aged 18-48, mean 25.1), 24 male workers (aged 18-32, mean 24.7) exposed to 268 mg/m3 (SD 185) toluene equivalent of mixed solvent (82.2% toluene, 12.3% ethyl acetate, and 5.5% methyl ethyl ketone) for 2.3 years (SD 3.0) compared with 24 matched controls (aged 17-31, mean 24.3), and 94 dentists (aged 24-49, mean 31.7) exposed to 0.017 mg/m3 (SD 0.009) of elemental mercury for 7.4 years (SD 5.3) compared with 54 referents (aged 23-50, mean 33.6) were studied. The Z score (made up of Digit Span, Symbols Digit, and Grooved Peg Board) for the workers exposed to toluene was 0.79, for workers exposed to mixed solvents was 0.38, and for the dentists exposed to mercury was 0.42. The Z score for each group of exposed subjects was statistically poorer than that for its controls. Neurobehavioral performance was statistically related to exposure intensity for the toluene-exposed workers and to years of exposure or dose (exposure intensity x years of exposure) for mixed solvent- and mercury exposed subjects. The type of chemical species and pattern of exposure appear to influence whether the adverse effects will be cumulative. PMID- 8472658 TI - Dose-dependent increase in subjective symptoms among toluene-exposed workers. AB - A factory survey on dose-response relationship in toluene toxicity was conducted in 1985-1989 in four cities in China. The examination items consisted of personal diffusive sampling for TWA exposure measurement, questionnaires on subjective symptoms, hematology and serum biochemistry, and clinical examination including simple neurology tests. Hippuric acid was also determined in urine samples collected at the end of the shift. With selection criteria that (1) complete results were available on all study items and (2) valid toluene exposure data (i.e., toluene shared 90% or more of the exposure) were obtained for the exposed, 452 toluene-exposed workers (206 men and 246 women; toluene exposure at 24.7 ppm as GM) and 517 nonexposed controls (246 men and 271 women) were selected. The subjective symptoms increased in close association with the intensity of exposure to toluene; the threshold concentration appeared to exist at 100 ppm in the case of symptoms during work, and it might be at 50-100 ppm when symptoms off work were evaluated. During the work with exposure at higher concentrations, various symptoms possibly related to CNS or local effects (e.g., eyes, nose, and throat) were complained, and dizziness and floating sensations were identified as typical symptoms with significant dose-response relationship. Several symptoms persisted off work, most of which were apparently related but not necessarily limited to CNS effects. Hematology and serum biochemistry were essentially negative. PMID- 8472659 TI - Change in hen sciatic nerve calcium after a single oral dose of tri-o-tolyl phosphate. AB - Six trace elements were monitored in neural tissue homogenates from White Leghorn hens orally dosed with tri-o-tolyl phosphate (TOTP) or tri-m-tolyl phosphate (TMTP) (200 mg/kg). Treated birds were monitored daily for development of delayed neurotoxicity, and concentrations of calcium, copper, iron, magnesium, manganese, and zinc were measured with atomic absorption spectroscopy at the time of maximal locomotor impairment (27-35 days postdosing). TOTP-treated birds manifested motor deficit by 15 days postdosing, while hens administered TMTP exhibited no signs of delayed neurotoxicity. Total calcium content in the sciatic nerve homogenates from TOTP-dosed hens was significantly less (P < 0.05) at the time of maximal locomotor impairment, while no shifts in the other trace elements were found. Therefore, the ortho isomer of tritolylphosphate elicited symptoms of delayed neurotoxicity in the hen (i.e., organophosphorus ester-induced delayed neurotoxicity or OPIDN) and caused a decrease in total calcium content in the sciatic nerve homogenates, in contrast to effects of the meta isomer. Analysis of neural homogenates at time of maximal locomotor impairment reflected secondary events in the degradative processes, since the initial assault of TOTP happens early after administration. Therefore, at fully developed OPIDN alteration of calcium balance in sciatic nerves is an indicator of axonopathy in a degenerated nerve following chemical injury. PMID- 8472660 TI - Three-dimensional brain metabolic imaging in patients with toxic encephalopathy. AB - Thirty-three workers, ages 24 to 63, developed clinical toxic encephalopathy after exposure to neurotoxins and were studied by SPECT brain scans. Five were exposed to pesticides, 13 were acutely exposed to mixtures of solvents, 8 were chronically exposed to mixtures of hazardous wastes that contained organic solvents, 2 were acutely exposed to phosgene and other toxins, and 5 had exposures to hydrogen sulfide. Twenty-nine had neuropsychological testing and all had a medical history and physical. Of the workers who had a clinical diagnosis of toxic encephalopathy, 31 (93.9%) had abnormal SPECT brain scans with the most frequent areas of abnormality being temporal lobes (67.7%), frontal lobes (61.3%), basal ganglia (45.2%), thalamus (29.0%), parietal lobes (12.9%), motorstrip (9.68%), cerebral hemisphere (6.45%), occipital lobes (3.23%), and caudate nucleus (3.23%). Twenty-three out of 29 (79.3%) neuropsychological evaluations were abnormal. Other modalities when performed included the following percentages of abnormals: NCV, 33.3%; CPT sensory nerve testing, 91.3%; vestibular function testing, 71.4%; olfactory testing, 89.2%; sleep EEG analysis, 85.7%; EEG, 8.33%; CT, 7.14%; and MRI brain scans, 28.6%. The complex of symptoms seen in toxic encephalopathy implies dysfunction involving several CNS regions. This series of patients adds to the previous experience of brain metabolic imaging and demonstrates that certain areas of the brain are typically affected despite differences in toxin structure, that these lesions can be globally defined by SPECT/PET brain scans, that these lesion correlate well with clinical and neuropsychological testing, and that such testing is a useful adjunct to previous methods. EEG and structural brain imaging such as CT and MRI are observed to have poor sensitivity in this type of patient. Additional metabolic imaging studies need to be done to explore dose, time, and specific toxin effects as well as mechanisms of toxicity and olfactory migration. PMID- 8472662 TI - A reproducible trigger for the measurement of trigeminal latencies elicited by a glabellar tap. AB - In order to develop a screening test of trigeminal latencies which could be used in the field, a stimulator which delivered a "tap" consisting of a focused puff of air to the glabella was compared with a tap delivered by means of a lightweight hammer with a piezoelectric trigger similar to that described by Shahani (Shahani and Young, 1972, Neurology 22, 149-154). Results were similar for both methods although the mechanical tap failed to elicit a response from the left side in one subject. The benefit of the air tap is in the reproducible force of the tap and better aim than is possible with the hammer. PMID- 8472661 TI - Psychological effects of low exposure to mercury vapor: application of a computer administered neurobehavioral evaluation system. AB - A computer-administered neurobehavioral evaluation system in a Chinese language version (NES-C) and a mood inventory of the profile of mood states (POMS) were applied to assess the psychological effects of low-level exposure to mercury vapor in a group of 88 workers (19 males and 69 females, with mean age of 34.2 years) exposed to mercury vapor (average duration of exposure 10.4 years). The well-matched group of 97 nonexposed workers was treated as the control. The intensity of current mercury vapor was relatively mild as reflected by the average level of mercury in the air of the workplace (0.033 mg/m3) and in urine (0.025 mg/liter). The results indicated that the profile of mood states posed was moving to the negative side in Hg-exposed group and most of the NES-C performances, in particular, the mental arithmetic, two-digit search, switching attention, visual choice reaction time, and finger tapping, were also significantly affected compared with those obtained from controls (P < 0.05 0.01). The present study and the previous study on the validation of the system suggest that the NES-C we developed is valid for the neurotoxicity screening among the working population exposed to neurotoxic agents. PMID- 8472663 TI - Pulmonary function in asbestosis and asbestos-related pleural disease. AB - This review begins with the classic physiologic syndrome of interstitial lung disease (ILD) described in established asbestosis in the 1950s: reduced VC and pulmonary compliance, maintenance of airflow (measured indirectly), decreased diffusing capacity (a laborious undertaking in those years), and hyperventilation, increased dead space (VD/VT), and desaturation on exercise. Small airways dysfunction (SAD) was recognized in the 1960s and 1970s as the physiologic counterpart of the early peripheral bronchiolar inflammatory and fibrotic narrowing reported in experimental animals and in asbestos workers. SAD is nonspecific and is often overshadowed by more severe obstruction caused by smoking or by the countervailing effects of increased lung recoil caused by interstitial fibrosis. Airtrapping secondary to SAD may explain some of the reduction in VC in asbestos exposed workers whose FEV1/FVC is normal. There may be a greater frequency of obstructive airways disease in asbestos workers who smoke than in other smokers, suggesting an interaction between these two noxious inhalants. An interaction is seen in the greater frequency and severity of radiographic asbestosis in smokers at equivalent durations of exposure and in the greater reduction in FVC in smokers at equivalent ILO profusion scores. The functional importance of PT is well documented by lower values for FVC at equivalent profusions of parenchymal disease. This is true of circumscribed PT but much more so of diffuse PT, which can occasionally result in ventilatory failure and death. Incremental exercise testing often reveals evidence of excessive ventilation and abnormal gas exchange (VD/VT) attributable to ILD, when standard tests of pulmonary function and chest radiography are normal. These abnormalities help explain dyspnea in such patients. PMID- 8472664 TI - Acute and chronic neurological symptoms among paint workers exposed to mixtures of organic solvents. AB - The purpose of this study was to determine the prevalence rates of acute and chronic neurologic symptoms among paint workers and the association of such symptoms with the severity of exposure to mixtures of solvents. Two paint manufacturing factories and 25 various kinds of spray painting factories were selected for study. Air concentrations of organic solvents were measured by personal samplers and were analyzed by gas chromatography. A total of 196 workers were given a screening neurological examination and a questionnaire on acute and chronic neurologic symptoms. A detailed personal medical history and a profile on alcohol consumption and medication were also included. The results showed that xylenes and toluene were the major solvents found in almost all the air samples with average contents of 50 and 24% on a weight basis of 73 air samples. We classified workers according to different exposure patterns and different air concentrations of breathing zones: high (8-hr hygienic effect, 0.25-9.86; median, 1.66), short-term high (hygienic effect, 0-3.38; median, 0.12), and low (hygienic effect, 0-0.38; median, 0.12). All workers showed no overt neurological signs such as ataxic gait, poor coordination, or muscle weakness. After excluding those workers who consumed more than 280 g of alcohol per week (n = 8), took antihypertensive medications (n = 4), or were treated with antipsychotic agents (n = 1), we found that the severity of exposure was associated with acute symptoms of headache and chest tightness and chronic symptoms of dizziness, easy fatigability, depressed mood, and palpitation. There was no association between peripheral neurological symptoms and the severity of exposure. Workers in the high exposure group were 2.7 times more likely to develop two or more acute symptoms and 3.3 times more likely to develop three or more chronic symptoms of the central nervous system than the low exposure group. After modeling by multiple logistic regression, we concluded that exposure to a medium level of mixtures of solvents (hygienic effect exceeding 1.66) may produce acute and chronic central neurological symptoms. PMID- 8472665 TI - Magnetic resonance imaging (MRI), neurobehavioral testing, and toxic encephalopathy: two cases. AB - The objective of this investigation was to examine cerebral magnetic resonance imaging (MRI) pathology and functional deficits demonstrated by neuropsychological testing in cases of toxic encephalopathy. Two subjects, occupationally exposed to toxic chemicals, were studied. As part of their neurological assessment, MRI was done and each underwent a neuropsychological battery for patients with toxic exposures (White et al. Clin. Neuropharmacol. 13(5), 392-412, 1990). In Case 1, who was exposed to inorganic mercury, MRI showed mild central and cortical atrophy. Punctiform foci (T2) were noted in both frontal regions underlying the precentral gyri and in the subcortical myelin. Neuropsychological testing showed problems in cognitive flexibility, cognitive tracking, inhibiting perseveration, fine manual motor coordination, visuospatial analysis and organization, memory, and affect and personality. In Case 2, who was exposed to 2.6-dimethyl-4-heptanone, MRI showed multiple small foci in the white matter and pons. Neuropsychological testing indicated affective changes, deficits in manual motor speed, verbal fluency, visuospatial organization, and short-term memory. Lack of aphasia in patients with toxic encephalopathy indicates that neurotoxins probably affect subcortical and mesial temporal structures more than cortical gray matter. These MRI studies show subcortical sites of pathology. PMID- 8472666 TI - Covariates of computerized neurobehavioral test performance in epidemiologic investigations. AB - Computerized neurobehavioral tests are being used increasingly in occupational and environmental health to measure potential effects of exposure to neurotoxicants. Many factors affect performance on these tests. Data sets from application of a computerized neurobehavioral evaluation system in epidemiologic investigations of two occupational groups, printing pressmen and construction painters, were analyzed. Age and education were the major covariates of performance in these groups. The reliability of these computerized tests was also reviewed. Computerized neurobehavioral tests are similar to conventional tests in terms of reliability and relationships to known covariates. PMID- 8472667 TI - Occupational exposure to neurotoxicants: preliminary survey in five industries of the Camacari Petrochemical Complex, Brazil. AB - The Camacari Petrochemical Complex (CPC) is the biggest and most important industrial complex of the northeastern region of Brazil. At present, its 54 companies employ directly and indirectly about 50,000 people. Used there as solvent and raw material, compounds such as benzene and its homologues n-hexane, haloalkanes, and some alcohols have as their prime targets the central and peripheral nervous systems. Despite widespread use of these chemicals, the workers are little aware of their toxicity, and the evaluation of exposure to them has only recently become a worrisome issue. This paper discusses the contamination of occupational environments in some industries of the CPC, as well as the neurobehavioral impairment that could be found among their workers. PMID- 8472668 TI - Effect of carbon tetrachloride on allylnitrile-induced head twitching. AB - Allylnitrile is known to induce head twitching in rats and mice. Carbon tetrachloride (CCl4) impairs the hepatic mixed function oxidase system and lowers acute toxicity of nitriles. In the present study we examined the effect of CCl4 on the allylnitrile-induced head twitching to elucidate the mechanism of the abnormal behavior. In rats, CCl4 pretreatment inhibited the head twitching induced by allylnitrile (1.49 mmole/kg, po), the maximal and dose-dependent inhibition occurring when CCl4 was given just prior to the nitrile administration, while CCl4 post-treatment had no effect on the head twitching. A dose-dependent inhibition of cyanide formation arising from allylnitrile in the liver and a dose-dependent attenuation of acute toxicity of allylnitrile were observed when CCl4 was given just prior to the nitrile administration in rats and mice. Intracerebroventricular injection of allylnitrile (2.0 to 18 mumole/brain) induced no head twitching in rats. The results suggest that active metabolites of allylnitrile are responsible for the head twitching, and that CCl4 prevents the metabolic process in the liver by forming conjugates with allylnitrile, resulting in the inhibition of the head twitching. PMID- 8472669 TI - Evaluation of the critical value of driving fatigue based on the fuzzy sets theory. AB - Applying the newly developed multistage evaluation method based on the fuzzy sets theory, we have evaluated the sense of driving fatigue of 8 male drivers who covered 400 km in 8 hr in the daytime, empirically revealing the distribution of the degree of driving fatigue. The critical values from "no" to "a bit" and "a bit" to "fatigued" are 1 and 5.5 hr, respectively. Finally, a tentative study of the psychophysical relations between driving time and driving fatigue has been made, leading to a curve of driving fatigue under the conditions of this experiment. PMID- 8472670 TI - Strategies for the prevention of environmental neurotoxic illness. AB - Toxic chemicals in the environment can cause a wide range of neurological disease. High-dose exposures to environmental neurotoxicants have produced encephalopathy in children ingesting chips of lead-based paint, blindness in persons who ingested methanol, blindness and ataxia in persons who consumed organic mercury, spinal cord degeneration and peripheral neuropathy in persons exposed to tri-ortho-cresyl phosphate (TOCP), and Parkinsonism in persons exposed to MPTP or to manganese. Environmental neurotoxicants have also been shown to produce a wide range of subclinical neurotoxic effects, including reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alternation of behavior. The first step in the prevention of environmental neurotoxicity is to test chemicals for their toxic potential. More than 70,000 chemicals are currently in commerce. However, except for pharmaceuticals, fewer than 10% of these chemicals have been tested for neurotoxicity. A logical approach to neurotoxicologic assessment of chemical substances will build on and extend currently available test systems. It will have a tiered structure. The first or screening tier will consist of tests to measure obvious structural and functional changes, often a functional observational battery. Subsequent levels of testing will be guided by the results of initial screening. Toxicologic testing must be supplemented by epidemiologic surveillance of populations exposed to known and suspect neurotoxicants. Screening programs in these populations designed to detect excessive absorption of a neurotoxic agent or subclinical neurological dysfunction can be useful in identifying affected individuals before severe disability occurs. PMID- 8472671 TI - Assessing the neurotoxic potential of chemicals--a multidisciplinary approach. AB - Since 1981, the development of methodology to assess the neurotoxic potential of chemicals has been a high priority within the International Programme on Chemical Safety (IPCS). Following the completion of an in-depth review of the scientific principles and methods for the assessment of neurotoxicity associated with chemical exposures, IPCS started to develop a multidisciplinary and comprehensive approach for neurotoxicity testing of chemicals. In view of the complexity of the nervous system and the variety of effects caused by chemicals, no single test or approach will be appropriate. Initially, IPCS evaluated neurobehavioral tests as well as in vitro procedures as screening tests, and an international collaborative study of neurobehavioral tests appropriate for screening chemicals for neurotoxicity is now in progress. Possible integration of higher level neurobehavioral tests with neurophysiological, biochemical, and pathological procedures in future testing strategies are discussed. PMID- 8472672 TI - Neurobehavioral effects of intrauterine mercury exposure: potential sources of bias. AB - Sources of bias were examined in a study of neurobehavioral effects of intrauterine exposure to methyl mercury in the Faroe Islands. The cohort of 1000 children was born during a 21-month period and did not differ from Faroese births in general as regards major obstetrical parameters. However, high mercury concentrations in the cord blood was associated with increased birth weight, presumably because other constituents of marine fish may cause a prolongation of the gestation period. Thus, children with high mercury exposures were somewhat protected against low birth weight and its associated neurobehavioral risks. Less than 25% of the women indicated occasional alcohol drinking during pregnancy, thus suggesting a limited fetal exposure to this neurobehavioral risk factor. However, maternal alcohol drinking caused a decrease in mercury concentrations in cord blood, probably because of a toxicokinetic interaction between ethanol and mercury. Any alcohol-related effect on neurobehavioral development would then be associated with lower levels of mercury exposures. The effects of these confounders would tend to bias the results of the study toward the null hypothesis. PMID- 8472673 TI - Mortality from working in the aluminum reduction industry. AB - Next to oxygen and silicon, aluminum is the most common element on this planet's surface. Studies of potential carcinogenics in aluminum workers have been reported to be equivocal, and consequently can give rise to serious global concern. However, studies have not taken into consideration smoking histories. Also a review of published articles suggests that the conclusions have been unduly conservative, and that criteria for causation have not been met. PMID- 8472674 TI - Respiratory findings among millwright and machinery erectors: identification of health hazards from asbestos in place at work. AB - Asbestos-associated diseases are prevalent in the construction trades primarily because of the previously widespread use of asbestos-containing insulation materials. Workers in metal-related trades, employed at construction sites and power facilities, but who do not routinely handle such materials as part of their work, may also be at risk for significant asbestos exposure. In order to evaluate such risk, a clinical field survey was conducted of 110 millwright and machinery erectors from the New York metropolitan area. A high prevalence of chest roentgenologic abnormalities was found. Forty-nine (44.5%) of the examined workers had pleural abnormalities consistent with asbestos-induced effects. Eighteen workers showed evidence of unilateral pleural thickening. Duration from onset of employment was significantly longer for those with pleural abnormalities (mean 32.3 years) as compared to those with normal chest radiographs (mean 18.5 years). Thirteen workers (11.8%) had radiographic signs of interstitial lung disease. The workers with pleural abnormalities had lower mean values of restrictive and obstructive lung function parameters than those with normal pleura. Multivariate and logistic regression analyses demonstrated association between duration of employment in the millwright trade and pleural abnormalities which was independent of smoking status. These findings suggest that millwright and machinery erectors employed in work environments where there is potential for primarily indirect exposure to airborne asbestos-containing dust are at risk for adverse effects from such exposure. PMID- 8472675 TI - Effects of neurotoxins on brain creatine kinase activity. AB - The effects of ethylene oxide (EO), acrylamide, N,N'-methylene-bis-acrylamide (bis-acrylamide), and methyl mercury chloride (MMC) on brain creatine kinase (CK) activity were examined in vivo. EO and acrylamide, both of which cause central peripheral distal axonopathy, inhibited CK activity in the brain and spinal cord. On the other hand, neither bis-acrylamide, a nonneurotoxic analogue, nor MMC which causes neuronopathy affected brain CK activity significantly. The inhibition of CK may play a role in the pathogenesis of distal axonal degeneration in the central and peripheral nervous systems. PMID- 8472676 TI - Effects of methyl mercury in postnatal developing rats. AB - Rats on Postnatal Days 1 (PD 1), 14 (PD 14), and 35 (PD 35) were orally administered 0, 2.60, 3.64, 5.10, 7.14, and 10 mg/kg/day of methyl mercury chloride (MMC) for 10 consecutive days. Mercury (Hg) accumulation in the brain of the rats treated with 10 mg/kg/day of MMC for 10 consecutive days was highest in PD-14 rats, followed by PD-35 and PD-1 rats. Hg accumulations in the liver and kidney were lowest in PD-1 rats and increased markedly with development in postnatal phase. The effect of MMC treatment on body weight change was most severe in PD-35 rats. The body weight loss began on Day 5 in PD-35 rats and on Day 10 in PD-14 rats treated with 10 mg/kg/day of MMC, but not in PD-1 rates under the same treatment. The phenomenon of hindlimb-crossing was induced on Day 11 in PD-14 rats and on Day 14 in PD-35 rats treated with 10 mg/kg/day of MMC, but was not observed in PD-1 rats. The deficit of rotarod performance was apparent only at the dose of 7.14 mg/kg/day of MMC in PD-35 rats, whereas rotarod performance was dose-dependently inhibited by MMC treatment in PD-14 rats, and lowered even at the dose of 2.6 mg/kg/day of MMC. However, the performance was gradually restored to the control level by 1 month except in rats given 7.14 mg/kg/day of MMC. These findings indicated that the Hg distribution and the effects of MMC treatment on body weight gain and motor coordination were different among the rat postnatal developing phases. PMID- 8472677 TI - Effects of ozone and nitrogen dioxide on drinking and eating behaviors in mice. AB - Male ICR mice were exposed continuously to ozone (O3) and nitrogen dioxide (NO2) for 7 days to examine the effects on drinking and eating behaviors. Ozone at 0.1 ppm did not affect drinking and eating activities, whereas drinking activity decreased in a concentration-dependent manner to 47.7, 12.8, and 3.0% of the control value with 2-day exposures to 0.2, 0.4, and 0.8 ppm O3, respectively, and eating activity decreased to 35.2 and 8.7% of the control value at 0.4 and 0.8 ppm O3, respectively. Body weight also decreased markedly by 2.0, 4.6, and 7.5 g at 0.2, 0.4, and 0.8 ppm O3, respectively. These decrements reached a maximum on the second day of exposure. However, alterations in drinking and eating activities and body weight were transient, leading to recovery during the continuous O3 exposures. The recovery processes were dependent on the concentrations of O3. Nitrogen dioxide at 4 ppm did not affect drinking and eating activities, whereas drinking activity decreased in a concentration dependent manner to 56.8, 8.3, and 18.7% of the control value with 2-day exposures to 6, 8, and 12 ppm NO2, respectively, and eating activity decreased markedly to 21.8 and 16.4% at 8 and 12 ppm NO2, respectively. Body weight also decreased by 2.5, 5.5, and 6.1 g at 6, 8, and 12 ppm NO2, respectively. These decrements reached a maximum on the second day of exposure. As in the O3 exposures, the decrements in drinking and eating activities and body weight were transient and recovered during the continuous exposures to NO2 depending on the concentrations of NO2. Drinking and eating activities and body weights of mice that had been previously exposed to 12 ppm NO2 for 7 days did not show changes when the mice were exposed to 0.4 ppm O3 9 days after NO2 exposure. The present study demonstrates that photochemical oxidants suppress drinking and eating behaviors in mice and that they recover thereafter under the continuous exposure conditions. PMID- 8472678 TI - Effects of toluene administration on delayed matching-to-sample performance in the pigeon. AB - Four pigeons were trained using a delayed matching-to-sample task. This task was composed of identity matching-to-sample trials and oddity from sample trials. In the case of identity trials, pigeons were required to choose the same stimulus as a sample to reach a food reward, and in the case of oddity trials, they had to choose a different stimulus from a sample to gain a food reward. After the performance became stable, toluene was administered intramuscularly at dosages of 10, 20, 40, and 80 mg/kg and tests were executed. The dosage of 10 mg/kg toluene caused increases in the percentage of correct responses in the 5- and 10-sec delay intervals, and 20 and 40 mg/kg toluene injections also increased the correct responses to some extent. At the dosage of 80 mg/kg toluene, the correct responses decreased and the performance was impaired. Toluene administration at relatively low dosages, especially 10 mg/kg, seemed to have excitatory effects on the CNS in pigeons, and presumably its arousal actions activated memory processes. PMID- 8472679 TI - International comparison of odor threshold values of several odorants in Japan and in The Netherlands. AB - The purpose of this paper is to compare the published odor threshold values of six odorants. In Japan, all of the odor threshold values used in the Offensive Odor Control Law (enacted in 1972) were determined in an odor-free room (4 m3) by a trained panel (20 men, ages 30-45 years who were perfumers) who sniffed the odors directly and made absolute judgments of odor quality and intensity. In The Netherlands, sensorial odor concentration measurements were made with an olfactometer in a mobile sniffing car with eight panelists, four men and four women, ages 18-40 years. Such presentations are repeated with different dilution ratios. Comparison of the threshold data for the six different compounds given as the barely perceptible concentration level revealed striking similarities for hydrogen sulfide (in Japan 0.0005 ppm/in The Netherlands 0.0003 ppm), phenol (0.012/0.010), styrene (0.033/0.016), toluene (0.92/0.99), and tetrachloroethylene (1.8/1.2) but not for m-xylene (0.012/0.12). Such a similarity was not found with any other literature sources. PMID- 8472680 TI - Nervous system effects of occupational exposure to styrene: a clinical and neurophysiological study. AB - Quantitative EEG of 99 workers occupationally exposed to styrene was analyzed and compared to exposure parameters. All of the workers came from reinforced plastics industry. The workplaces and factories were previously evaluated, and the exposure levels were known rather accurately. The exposure information form workplaces and the individual exposure data were combined to form an Exposure Index, which reliably reflected long-term exposure to styrene in various occupational settings. All of the subjects underwent careful medical, neurological, and neurophysiological examinations. Quantitative EEG was recorded from 19 channels and analyzed for absolute and relative power, asymmetry, coherence, frequency distribution, and statistical normative database comparisons (Neurometrics). The EEG data showed a significant increase of abnormal EEG classifications in workers with higher exposure. When the workers were divided into two groups, based on the exposure data, those with higher exposure had higher absolute EEG power in alpha and beta bands in the frontotemporal regions of the brain. The findings indicate that abnormalities in cerebral function can be demonstrated even with relatively low mean exposure levels. It is concluded that the efforts to lower the administrative hygienic levels of styrene have been in the right direction. PMID- 8472681 TI - Individual-administered human behavioral test batteries to identify neurotoxic chemicals. AB - Most research demonstrating behavioral effects of occupational chemical exposures is produced in established laboratories using a consistent set or battery of tests. Exemplifying this tradition are batteries developed at Finland's Institute of Occupational Health, Milan's Institute of Occupational Health, Sweden's National Institute of Occupational Health, Australia's National Institute of Occupational Safety and Health, and at universities in the United States and other countries. In 1983, under the World Health Organization (WHO) aegis, experienced human occupational researchers recommended the Neurobehavioral Core Test Battery (NCTB) as a screening instrument to be administered by an individual to subjects exposed to chemicals believed to be neurotoxic. Health professionals from 50 cities in 27 countries distributed on every large continent have been trained to administer the NCTB according to its Operational Guide. Six issues need to be addressed regarding human-administered test batteries: (a) The critical role of individual-administered batteries to screen chemically exposed populations in a field increasingly dominated by computer-administered batteries; (b) selection criteria for tests to assess known and unknown chemicals; (c) utility of baseline data for study analysis and interpretation; (d) test battery validation; (e) availability and cost of inexpensive test batteries; and (f) equivalence of computer- and human-administered variants of the same tests. PMID- 8472682 TI - Can visual perception be used to estimate body part angles? AB - For two decades, observational methods have been used to measure postural loads in industry. These methods depend on the analyst's judgment to characterize correctly the working postures. The errors associated with estimating the body part's angular deviation from the neutral position are not known. Recently, videotaping of a work situation, followed by examination of the tape to assess postural position has become more commonly practised. This study was conducted to determine the error which accompanies the judging (without tools) of postural angles. In the present study, a method was used whereby 20 subjects were asked to report the perceived angles which closely matched the actual shoulder flexion angle displayed on the TV screen. The results showed no significant differences among the three angular ranges ('low', 1-60 degrees; 'medium', 61-120 degrees; and 'high', 121-180 degrees) of shoulder flexion, in terms of algebraic and absolute errors. Subjects tended to slightly overestimate the true angle in the low range and to slightly underestimate the true angle in the medium and high angle ranges. This study suggests that visual perception can be used to estimate shoulder flexion angles displayed on a VDT. PMID- 8472683 TI - Menstrual cycle effects on a VDT-based simulation task: cognitive indices and subjective ratings. AB - It is unclear whether the menstrual cycle affects the basics of performance, mainly task performance and cognitive functions. We examined menstrual cycle effects on VDT-based task performance, cognitive indices based on the signal detection theory, and subjective ratings in questionnaires. We experimented in three phases: premenstrual, menstrual and postmenstrual phases. Previous studies reported premenstrual tension syndrome (PMST) in the premenstrual phase. Women used physiological and psychological strategies to cope during the menstrual phase. However, task performance, cognitive indices and subjective ratings showed no menstrual cycle effects. Thus, we can conclude that the information processing for the VDT-based task was not affected by menstrual cycle. PMID- 8472684 TI - Wrist motions in industry. AB - Cumulative trauma disorders (CTDs) are disorders of the body's tendons and nerves due to repeated exertions and excessive movements. Workers in industrial tasks who have to move their hands and wrists repeatedly and/or forcefully are susceptible to CTDs. One of the major research voids in the study of occupational wrist CTDs is the lack of quantification of the relationship between the known kinematic risk factors, such as wrist angle and repetition, and CTD risk. A quantitative surveillance study was performed in industry in which workers' three dimensional wrist motions were monitored on the factory floor. A total of 40 subjects from eight industrial plants participated in this study (20 workers in each of two risk groups, low and high). The wrist motion parameters that were monitored for each subject were position, angular velocity, and angular acceleration measures in each plane of movement (radial/ulnar, flexion/extension, and pronation/supination). Descriptive analyses of these measures indicated that generally the mean of the high-risk subjects was larger in magnitude than that of their low-risk counterparts. However, only the velocity and acceleration parameters resulted in significant differences between low- and high-risk groups. These results demonstrate the importance of dynamic components in assessing CTD risk. PMID- 8472685 TI - The effects of biofeedback on carpal tunnel syndrome. AB - Behaviour modification based on audible electromyographic (EMG) biofeedback signals was used to discourage the awkward hand postures and the exertion of excessive force with the fingers, which are suspected of causing carpal tunnel syndrome (CTS). The null hypothesis was that participation in such a biofeedback programme has no effect on CTS symptoms. Before and during an 8-week study, data were collected from two groups of five female assembly line workers each. The biofeedback group received training and input, while the control group did not. Test results indicated that the null hypothesis could not be rejected. PMID- 8472686 TI - An analytical method for characterizing repetitive motion and postural stress using spectral analysis. AB - The availability of small, inexpensive electrogoniometers has made wrist posture measurement during repetitive manual work practical. Efficient analytical methods, however, are not currently available for quantifying the degree of repetitiveness and the interaction with postural stress. Spectral analysis was investigated as a method for characterizing repetitive wrist motion and postural stress using a simple peg transfer task. Wrist posture was controlled by adjusting the pegboard location and by having subjects reach over an obstruction. Work pace was externally controlled using an auditory signal. Angular wrist flexion/extension and ulnar/radial deviation was recorded using a 60 Hz sample rate. Power spectra were computed by stratifying data segments into individual work elements, divided by break points associated with the task. Peak spectral magnitudes and frequency components corresponded closely with joint displacement amplitudes and repetition rates. Spectrum DC component magnitudes were directly related to sustained wrist postures. PMID- 8472687 TI - Static force exertion in postures with different degrees of freedom. AB - In assessing human force exertion, the use of standardized postures can lead to the inaccurate prediction of the forces and postures which occur in everyday life. Therefore force data obtained using postures freely chosen by subjects themselves may be considered more relevant. A standardized posture, however, is considered to yield more reliable data. The question arose whether it would be possible to combine the two in some way, calling the result a 'functional posture'. Research was necessary to determine a way of operationalizing these functional postures, and to test their reproducibility. First, a method is proposed to describe functional postures through explorative research. This includes the fixation of members that transfer force to the outside world, while the rest of the body is allowed to move freely. The results of further research show that the exerted force is reproducible in free, functional, and standardized postures. The difference in average force, though, is considerable and significant. The conclusion is that force exertion in free posture is most suitable for design research. PMID- 8472688 TI - Spectral analysis of erector spinae EMG during intermittent isometric fatiguing exercise. AB - The applicability of EMG spectral analysis in the study of muscular fatigue of the erector spinae muscle was investigated. At three locations (L1, L2, L5) of the erector spinae muscle, representing different functional parts, EMG was sampled during fatiguing intermittent isometric extension of the trunk. The multifidus muscle (L5) appeared to show the most consistent changes of the EMG power spectrum as a consequence of fatigue. Whether the effects of the increase in muscle temperature on the power spectrum could be eliminated by low-pass filtering the data (60 Hz and 40 Hz) was also investigated. It was expected that this would make it possible to detect better the effects of fatigue on the firing characteristics of the motorunits by the inherent changes in the power spectrum. Low-pass filtering did not cause a more significant trend of the median frequency of the power spectrum. Future research will have to explore which parts of the power spectrum are affected by an increase of the muscle temperature. PMID- 8472689 TI - Spinal compression tolerance limits for the design of manual material handling operations in the workplace. AB - Spinal compression tolerance limits (SCTL) have been widely used by ergonomists in setting work tolerance limits for manual materials handling (MMH) operations. Thus, the effect of personal and experimental factors on spinal compression tolerance limits (SCTL) is reviewed with the aid of regression and correlation analyses performed on data compiled from the published literature. Tables of SCTL from various sources utilizing large number of specimens and personal factors are presented so that they can be accessed by ergonomists easily. Integrated biomechanical guidelines based on SCTL are provided for the design of MMH operations in the workplace. It is suggested that, in order to reduce the probability of MMH injuries, biomechanical tolerance limits should be set at the damage load instead of the load at fracture. The damage load is the weight which causes the first gross signs of damage such as tissue fluid and blood. An algorithm is described to demonstrate the use of a biomechanics approach to the design of MMH operations. PMID- 8472690 TI - Effect of prior exercise at different pedalling frequencies on maximal power in humans. AB - The effect of prior submaximal exercise performed at two different pedalling frequencies, 60 and 120 rev.min-1, on maximal short-term power output (STPO) was investigated in seven male subjects during cycling exercise on an isokinetic cycle ergometer. Exercise of 6-min duration at a power output equivalent to 92 (SD 5)% maximal oxygen uptake (VO2max), whether performed at a pedalling frequency of 60 or 120 rev.min-1, reduced maximal STPO generated at 120 rev.min-1 to a much greater extent than maximal STPO at 60 rev.min-1. After 6-min submaximal exercise at 60 rev.min-1 mean reductions in maximal STPO measured at 120 and 60 rev.min-1 were 27 (SD 11)% and 15 (SD 9)% respectively, and were not significantly different from the reductions after exercise at 120 rev.min-1, 20 (SD 13)% and 5 (SD 9)%, respectively. In addition, we measured the effect of prior exercise performed at the same absolute external mechanical power output [236 (SD 30)W] with pedalling frequencies of 60 and 120 rev.min-1. Although the external power output was the same, the leg forces required (absolute as well as expressed as a proportion of the maximal leg force available at the same velocity) were much higher in prior exercise performed at 60 rev.min-1. Nevertheless, maximal STPO generated at 120 rev.min-1 was reduced after exercise at 120 rev.min-1 [20 (SD 13)%, P < 0.05] whereas no significant reduction in maximal STPO was found after prior exercise at 60 rev.min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472691 TI - Comparison of muscle sympathetic nerve activity during exercise in dominant and nondominant forearm. AB - To determine whether or not muscle endurance training alters exercise-induced sympathetic nerve response, we recorded muscle sympathetic nerve activity (MSNA) microneurographically during forearm exercise and compared MSNA between dominant (D) and non-dominant (ND) forearms of players of racket sports. Three kinds of forearm exercise were conducted on each side; static (SHG) and dynamic (DHG, at a rate of 1 Hz) handgrip exercise at a loading of 25% of maximal voluntary contraction until exhaustion, and 10-min submaximal dynamic handgrip (at a rate of 1 Hz) at an intensity of 0.9 W. Heart rate, ventilation and blood pressure were also monitored at rest and during SHG and DHG exercises. During the last minute of SHG exercise, MSNA burst rate had increased on average by 290 (SEM 46)% in D and 330 (SEM 46)% in ND, while during DHG it increased by 288 (SEM 38)% in D and 344 (SEM 36)% in ND, respectively. There were no significant differences in the MSNA responses between D and ND forearms in either exercise modes. Significant increases in heart rate, ventilation and blood pressure during the last minute of fatiguing SHG and DHG were observed, but there were no significant differences between the two forearms. During submaximal DHG, while MSNA increased significantly above control values in both D and ND, the MSNA response was less in D than that in ND forearm. The results would suggest that exercise-induced MSNA responsiveness is influenced little by muscle endurance training but the intensity of response may be due to the magnitude of metaboreceptor stimulation in the exercising muscle. PMID- 8472692 TI - H-reflexes are smaller in dancers from The Royal Danish Ballet than in well trained athletes. AB - The size of the maximal H-reflex (Hmax) was measured at rest and expressed as a percentage of the maximal M-response (Mmax) in 17 untrained subjects, 27 moderately trained subjects, 19 well-trained subjects and 7 dancers from the Royal Danish Ballet. The Hmax/Mmax was significantly larger in the moderately and well-trained subjects than in the untrained subjects but smaller in the ballet dancers. It is therefore suggested that both the amount and the type of habitual activity may influence the excitability of spinal reflexes. PMID- 8472693 TI - Effects of physical exercise on the elasticity and elastic components of the rat aorta. AB - To evaluate the effects of exercise on aortic wall elasticity and elastic components, young male rats underwent various exercise regimes for 16 weeks. In the exercised rats, the aortic incremental elastic modulus decreased significantly when under physiological strain. The aortic content of elastin increased significantly and the calcium content of elastin decreased significantly in the exercised group. The accumulated data from the exercised and sedentary groups revealed that the elastin calcium content was related positively to the incremental elastic modulus. We concluded that physical exercise from an early age decreases the calcium deposit in aortic wall elastin and that this effect probably produced in the exercised rats a distensible aorta. PMID- 8472694 TI - Effect of a high-carbohydrate diet intake on muscle glycogen repletion after exercise in rats previously fed a high-fat diet. AB - The effect of a high-carbohydrate (C) diet intake on muscle glycogen repletion during the early period of recovery from exercise was studied in rats previously fed a high-fat (F) diet. In experiment 1, 3 week-old male and in experiment 2, 3 week-old female rats were used. Rats were fed either the F or the C diet for 2-10 weeks ad libitum and then were meal-fed regularly twice a day for 25 days in experiment 1, or for 5 weeks in experiment 2. During the period of regular feeding, half of the rats in both dietary groups continued to eat as before (F-F and C-C) but the other half of the rats were switched to the counterpart diets (F C and C-F) in experiment 1. In experiment 2, half of the F-F group were switched to the C diet (F-C) for 3, 7, and 14 days after the period of regular feeding. Pre-exercise glycogen content in soleus, red gastrocnemius, and heart muscles and liver was higher in rats fed the C diet (C-C and F-C) than in rats fed the F diet (F-F and C-F) in experiment 1. Glycogen repletion in red muscle 2 h after the ingestion of a glucose and citrate (3.0 and 0.5 g, respectively, per kg body mass) drink was also higher in the former than in the latter. There was a positive relationship in skeletal muscles between pre-exercise glycogen content and the rate of glycogen repletion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472696 TI - Carbohydrate consumption prior to repeated bouts of high-intensity exercise. AB - Rapid depletion of muscle glycogen occurs during activities greater than 100% of maximal oxygen uptake. While carbohydrate ingestion prior to an endurance event has been shown to be beneficial, the effects of carbohydrate ingestion on repeated bouts of high-intensity exercise are not known. Therefore, the purpose of this study was to determine if carbohydrate ingestion prior to repeated bouts of high-intensity, short-duration exercise would improve performance. Ten well trained male cyclists performed two experimental rides, one 15 min after consumption of 5.0 ml.kg-1 body weight of a 19.7% carbohydrate drink and one following a placebo. The experimental ride consisted of four 1.6 km timed performance rides separated by 4.8 km steady-state rides at 80% of maximal oxygen uptake (between the last two performance rides the steady-state rides were 1.6 km at 80% and 1.6 km at 90%). Blood glucose levels were significantly increased following both the ingestion of the carbohydrate beverage and the performance of the exercise bout. Total exercise time following ingestion of the experimental drink [mean (SD); 25.6 (3.3) min] was not different from that following ingestion of the placebo [25.2 (3.3) min]. Similarly, the sum of all four timed performance rides following ingestion of the experimental drink [6.8 (0.9) min] was not different from that following ingestion of the placebo [6.6 (0.9) min]. In the present study, carbohydrate ingestion 15 min prior to exercise increased blood glucose levels, although performance time was not affected. PMID- 8472695 TI - Rapid increase in the number of androgen receptors following electrical stimulation of the rat muscle. AB - The changes in the number of androgen receptors in rat gastrocnemius muscle following muscle contraction caused by electrical stimulation were investigated. The gastrocnemius muscle of one leg, which was selected at random for each rat, was stimulated with needle type electrodes, e.g. for 2 s at 10 V and 100 Hz, with 5-s intervals. The contralateral leg was left unstimulated as a control. One set consisted of ten such stimuli, followed by 5-min rest. Three sets every 2 days caused a statistically significant increase in muscle mass, the increase being about 2.5% after the 3rd day of stimulation, 4.4% after the 5th day, 5.9% after the 13th day and 8.3% after the 27th day compared with each control muscle (P < 0.001 in each case). The protein content also increased but the water content did not change. Stimulation over 4 weeks induced an increase in the area of the cross section of the muscle fibres to about 30% more than that of the control muscles, though the total muscle fibre numbers were slightly, but significantly, reduced. Electromechanical properties supported the development of the muscle by stimulation, because the maximal isometric tetanic force and peak twitch force markedly increased in the stimulated muscle. The androgen receptors in the muscle cytosol fraction were determined by means of a binding assay involving [3H]methyltrienolone, which is an analogue of testosterone, the number having rapidly increased in the stimulated leg, when compared with that in the control leg, by about 25% after the 3rd day. The increase then slowed down, reaching a plateau after the 5th-day of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472697 TI - The effects of acute altitude exposure in Swiss highlanders and lowlanders. AB - The functional characteristics at rest in responding to stepwise acute exposure to simulated altitude (6000 m) were compared in 10 acclimatized mountaineers (highlanders), residents of Zermatt (1616 m) working at an altitude up to about 4000 m, and in 11 nonacclimatized control subjects (lowlanders) living and working in Zurich (450 m). In comparison with the lowlanders, the highlanders showed at altitude significantly greater hyperventilation, lower heart rate and systolic blood pressure, smaller haemoconcentration, lower urodilatin secretion and natriuresis, and a preserved neuropsychological ability (attentiveness) and vasomotor tone (diastolic blood pressure); the critical altitude at which hypoxic short-term adaptation became insufficient was 6000 m. The lowlanders, however, manifested reduced tolerance of hypoxia, i.e. insufficient short-term adjustment with subjective and objective distress coinciding with the first signs of hypoxia of the central nervous system, already apparent at and above 4000 m. It was concluded that the functional differences between highlanders and lowlanders in responding to acute gradual hypoxia indicated factors contributing to altitude acclimatization. PMID- 8472698 TI - Relationship between cardiac output and oxygen uptake at the onset of exercise. AB - The purpose of the present study was to assess the relationship between the rapidity of increased gas exchange (i.e. oxygen uptake VO2) and increased cardiac output (Qc) during the transient phase following the onset of exercise. Five healthy male subjects performed multiple rest-exercise or light exercise (25 W) exercise transitions on an electrically braked ergometer at exercise intensities of 50, 75, or 100 W for 6 min, respectively. Each transition was performed at least eight times for each load in random order. The VO2 was obtained by a breath by-breath method, and Qc was measured by an impedance method during normal breathing, using an ensemble average. On transitions from rest to exercise, VO2 rapidly increased during phase I with time constants of 6.8-7.3 s. The Qc also showed a similar rapid increment with time constants of 6.0-6.8 s with an apparent increase in stroke volume (SV). In this phase I, VO2 increased to about 29.7%-34.1% of the steady-state value and Qc increased to about 58.3%-87.0%. Thereafter, some 20 s after the onset of exercise a mono-exponential increase to steady-state occurred both in VO2 and Qc with time constants of 26.7-32.3 and 23.7-34.4 s, respectively. The insignificant difference between Qc and VO2 time constants in phase I and the abrupt increase in both Qc and SV at the onset of exercise from rest provided further evidence for a "cardiodynamic" contribution to VO2 following the onset of exercise from rest. PMID- 8472699 TI - Myo-electric fatigue manifestations revisited: power spectrum, conduction velocity, and amplitude of human elbow flexor muscles during isolated and repetitive endurance contractions at 30% maximal voluntary contraction. AB - A brief survey of the literature on manifestations of myo-electric fatigue has disclosed a surprisingly sharp conflict between early studies, focusing on neuromotor regulatory mechanisms, and more recent studies which stress the determinant influence of local metabolism and skewed homeostasis. Favoured explanations concerning changes in the electromyographic (EMG) spectrum were synchronization/grouping of motor unit (MU) firing and conduction velocity (CV) decreases of the action potential propagation. The notion of mutual exclusivity interwoven with these theories prompted us to reinvestigate the EMG of moderate level, static endurance contraction. Ten men in their twenties performed isometric elbow flexion (elbow angle 135 degrees) at 30% maximal voluntary contraction (MVC), and the surface EMG of the brachioradialis (BR) and biceps brachii (BB) muscles was recorded. Initially the CV--determined by cross correlation--was 4.3 m.s-1 (BR) and 4.6 m.s-1 (BB). At exhaustion the CV of the BR muscle had declined by 33%, roughly twice the decrease of the BB CV. Substantially larger relative median frequency (fm) reductions of 50% (BR) and 43% (BB) were found. Simultaneously, the root-mean-square amplitudes grew by 150% (BR) and 120% (BB). All changes during contraction reached the same level of significance (P < 0.001, both muscles). From the largely uniform relative increases in fm and CV during the last 4 min of a 5-min recovery period, variations in CV were suggested to produce equivalent shifts in fm. The gradually increasing discrepancies between relative decreases in fm and CV during contraction presumably reflected centrally mediated regulation of MU firing patterns (notably synchronization). After the 5-min recovery another 11 endurance contractions at 30% MVC were executed, separated by 5-min intervals. The series of contractions reduced the endurance time to one-third of the 153 s initially sustained, while the terminal CV recordings increased by 1.0 (BR) and 0.6 (BB) m.s-1, and the terminal fm increased by 24 (BR) and 14 (BB) Hz. The relative CV decreased in direct proportion of the endurance time and the fm decreases varied with the CV; the findings did not support a causal link between CV decrease (signifying impaired fibre excitability) and the force failure of exhaustion. PMID- 8472700 TI - Daily activity and body temperature. AB - Body temperature varies between 36 and 39 degrees C in states ranging from sleep to high levels of sustained exercise, but it is not known whether this continuum of body temperature is related to a continuum of activity. Calorimetric studies of sedentary days were undertaken with four levels of food intake, men doing mild sustained exercise, and men and women walking and cycling vigorously. Steady states of metabolism were followed by slow exponential changes to steady states of heat loss (sigma Q), followed in turn by changes in rectal temperature (T(re)). Regression analysis showed a continuous, curvilinear relationship between sigma Q and T(re) from the low end of the activity spectrum (50 W) to progressively higher levels of exercise (600 W). These related continua of activity and body temperature appear to be the result of heat regulation. PMID- 8472701 TI - Isokinematic muscle mechanics in four groups of women of increasing age. AB - The purpose of this study was to evaluate the effects of age on dynamic muscle attributes of the knee extensors and flexors in postmenopausal women. Young healthy women (3rd decade, n = 15; 4th decade, n = 5) and older healthy women (6th decade, n = 9; 7th decade, n = 6) were tested at six angular velocities from 60 degrees.s-1 to 400 degrees.s-1. The 3rd and 4th decade groups produced greater extensor and flexor values for strength related variables at all angular velocities (peak torque, angle specific torque, work, power) than both the 6th and 7th decade groups (P < 0.05). However, relative changes in these variables, with increments in angular velocity, were equivalent among the groups. Analysis of the flexor: extensor ratios for these variables demonstrated a differential loss in flexor function with increased age, perhaps indicative of type II motor unit loss or muscle fibre atrophy. It is suggested that such changes may be present even within 4th decade subjects. PMID- 8472702 TI - Effect of endurance training on excessive CO2 expiration due to lactate production in exercise. PMID- 8472703 TI - A new method for the evaluation of anaerobic running power in athletes. AB - A new maximal anaerobic running power (MARP) test was developed. It consisted of n.20-s runs on a treadmill with a 100-s recovery between the runs. During the first run the treadmill speed was 3.97 m.s-1 and the gradient 5 degrees. The speed of the treadmill was increased by 0.35 m.s-1 for each consecutive run until exhaustion. The height of counter-movement jumps and blood lactate concentration ([la-]b) were measured after each run. Submaximal ([la-]b = 3 mmol.l-1 and 10 mmol.l-1) and maximal speed and power (W3mmol, W10mmol and Wmax, respectively) were calculated and W was expressed in oxygen equivalents according to the American College of Sports Medicine equation. Thirteen male athletes whose times over 400 m ranged from 47.98 s to 54.70 s served as subjects. In the MARP-test the speed at exhaustion was 6.89 (SD 0.28) m.s-1 corresponding to a Wmax of 118 (SD 5) ml.kg-1 x min-1. The peak [la-]b after exhaustion was 17.0 (SD 1.6) mmol.l 1. A significant correlation (r = 0.89, P < 0.001) was observed between the Wmax and the average speed in the 400-m sprint. The maximal 20-m sprinting speed on a track and W10mmol correlated with both the Wmax and the 400-m speed. It was concluded that the new method allows the evaluation of several determinants of maximal anaerobic performance including changes in the force-generating capacity of leg muscles and [la-]b relative to the speed of the sprint running. the [la-]b at submaximal sprinting speed was suggested as describing the anaerobic sprinting economy. PMID- 8472704 TI - Decision support by computer analysis of selected case history variables in the emergency room among patients with acute chest pain. AB - A computer system to be used in the emergency room has been developed for estimating the risk of acute coronary heart disease (ACHD). The system uses data on 38 case history and clinical variables collected consecutively over a year from 918 patients with acute chest pain. A statistical procedure based on Bayes' formula is used to estimate disease probabilities. A quadratic scoring rule was used for variable selection. The score increased markedly until 15-20 variables had been added, reached a maximum after inclusion of about 30 variables and then deteriorated slightly. Thus, the number of variables carrying additional information on the presence/absence of ACHD seems to be much larger than the number normally utilized by doctors and by other decision support systems. Reclassification into two groups, those with and without ACHD, gives a diagnostic accuracy of 89%. We conclude that analysing detailed case histories by computer is a promising decision support system for use in the emergency room as a supplement to ECG analysis. PMID- 8472705 TI - Prospective evaluation of an EDB-based diagnostic program to be used in patients admitted to hospital with acute chest pain. AB - A recently designed computer based decision support system (DSP), almost exclusively based on case history data, was developed to facilitate immediate differentiation between patients with and without urgent need for coronary care unit (CCU) transferral from the emergency room, and additionally to distinguish between patients with and without acute myocardial infarction (MI). One-year's prospective testing in a consecutive series of 1252 patients with acute chest pain revealed that the DSP, used in addition to ECG and clinical examination, demonstrated a sensitivity of 96% in the detection of patients in need of CCU observation (MI-sensitivity of 98%), and a specificity of 56% in excluding patients who were not in need of CCU observation. The proportion of referrals to the CCU judged to be unnecessary was only 17% of the total number of patients seen in the emergency room. PMID- 8472706 TI - Diagnosis of prosthetic heart valve thrombosis. The respective values of transthoracic and transoesophageal Doppler echocardiography. AB - Early diagnosis of acute prosthetic thrombosis remains a challenge. In 20 patients with 23 thrombosed cardiac valves, we evaluated the respective value of transthoracic (TTE) and transoesophageal (TEE) Doppler echocardiography. According to the presence or absence of prosthetic obstruction by continuous-wave Doppler, prostheses were separated into two groups. Group 1 included nine thrombosed prostheses (8 mitral, 1 aortic) with severe obstruction. All patients presented with severe symptoms of heart failure. Transthoracic Doppler echocardiography allowed immediate diagnosis of prosthetic thrombosis, even in critically ill patients, showing (1) eccentric transprosthetic colour flow jets in all eight mitral prostheses, (2) severe obstruction on Doppler examination (mean gradient = 18 to 36 mmHg in eight mitral prostheses, and 69 mmHg in one aortic valve), and (3) direct echocardiographic evidence of thrombosis (i.e. thrombus or abnormal disc or leaflet motion) in four patients. All nine patients were immediately treated by surgery (n = 8) or fibrinolysis (n = 1) on the basis of TTE results only. TEE allowed better visualization of thrombus and restricted leaflet or disc motion, but had little influence on patient management. Group 2 included 14 thrombosed prostheses (10 mitral, 4 aortic) with mild or absent obstruction. In three patients with massive mitral prosthetic thrombosis, an associated minimal thrombosis of a prosthetic aortic valve was found at surgery, but was detected neither by TTE, nor by TEE. The 11 remaining patients with isolated partial mitral (n = 10) or aortic (n = 1) thrombosis. Clinical presentation was fever, cerebral embolism, or mild dyspnoea, but no heart failure. TTE was normal in all.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472707 TI - Quantitation of global and regional left ventricular function by cine magnetic resonance imaging during dobutamine stress in normal human subjects. AB - Magnetic resonance imaging (MRI) provides high-resolution images of the heart. However, physical exercise during MRI is difficult due to space restriction and motion artefacts. To evaluate the feasibility of MRI during stress conditions, dobutamine was used as an alternative to exercise. Haemodynamics, ventricular volumes and wall thickening were measured at rest and during peak dobutamine infusion (15 micrograms.kg-1 x min-1) in 23 normal human subjects. To calculate left ventricular volumes, eight short-axis views were obtained encompassing the left ventricle from base to apex. At six levels, percent systolic wall thickening (%WTh) was measured in 18 segments (20 degrees intervals). Heart rate, systolic and diastolic blood pressures, stroke index, cardiac output and left ventricular ejection fraction increased significantly during dobutamine infusion (all P values < 0.001). In addition, %WTh increased significantly (P < 0.001) during dobutamine compared to the control state at all levels except in the apical and low-left ventricular levels. Both in control conditions and during dobutamine, segmental wall motion analysis showed the highest %WTh at the posterolateral area and the lowest %WTh at the septal region (P < 0.05). MRI clearly identifies wall motion dynamics and provides calculations of segmental wall thickening and haemodynamic parameters. Dobutamine is a useful stress agent by virtue of its safety, operator control and its effects which resemble physical exercise. PMID- 8472708 TI - Classification of electrocardiographic ST-T segments--human expert vs artificial neural network. AB - Artificial neural networks, which can be used for pattern recognition, have recently become more readily available for application in different research fields. In the present study, the use of neural networks was assessed for a selected aspect of electrocardiographic (ECG) waveform classification. Two experienced electrocardiographers classified 1000 ECG complexes singly on the basis of the configuration of the ST-T segments into eight different classes. ECG data from 500 of these ST-T segments together with the corresponding classifications were used for training a variety of neural networks. After this training process, the optimum network correctly classified 399/500 (79.8%) ST-T segments in the separate test set. This compared with a repeatability of 428/500 (85.6%) for one electrocardiographer. Conventional criteria for the classification of one type of ST-T abnormality had a much worse performance than the neural network. It is concluded that neural networks, if carefully incorporated into selected areas of ECG interpretation programs, could be of value in the near future. PMID- 8472709 TI - Derivation and validation of a new angiographic score of right coronary artery perfusion. AB - A semi-quantitative right coronary artery score (RCA score) was derived from the ratio of the number of the major left ventricular branches of the right coronary artery to the total of the right coronary and left circumflex arteries, to stratify the extent of perfusion in patients with right coronary artery dominance. Thirty-seven patients with one-vessel coronary disease involving a dominant right coronary artery proximal to the left ventricular branches were selected for study. Thallium scintigraphy was performed after right intracoronary injection in 11 patients, and 26 patients underwent conventional stress thallium scintigraphy (24 exercise thallium and two dipyridamole thallium scintigraphy). Thallium scores of perfusion region size after right intracoronary thallium injection and perfusion defect size in stress thallium studies were quantitated from planar thallium images. Both the RCA score and the regional thallium scores spanned over a wide range. The RCA score (range 0.23-0.85) correlated best with the posterior (70 degrees left anterior oblique view) plus lateral segment (40 degrees left anterior oblique view) thallium score (r = 0.88 and 0.53 for intracoronary and stress thallium studies respectively). It also correlated with the summed thallium scores in the posterior, lateral, apical and inferior segments (r = 0.73 and 0.54 respectively) but not with thallium scores in the apex or inferior segment alone. The proposed RCA score quantitates the variable posterolateral perfusion territory of the right coronary artery, and could stratify the area of myocardium at risk from coronary stenosis in the majority of patients with right coronary dominance. PMID- 8472710 TI - Effects of adrenaline on ventricular function and coronary haemodynamics in relation to catecholamine handling in transplanted human hearts. AB - We investigated cardiovascular and coronary responses to intravenous infusions of adrenaline, which raised arterial concentrations in a stepwise fashion from basal to about 5-6 nmol.l-1, in 11 non-rejecting heart transplanted patients, and in eight intact innervated subjects. Cardiac adrenaline extraction and noradrenaline release rate were also measured. The transplanted patients showed larger increases in heart rate (36 +/- 11% vs 16 +/- 6%, P < 0.0001) and cardiac index (80 +/- 30% vs 56 +/- 19%, P < 0.05), while stroke volume increments were similar in the two groups (32 +/- 17% vs 35 +/- 13%). The study groups did not differ with respect to changes in arterial pressure, cardiac work or peripheral resistances. Coronary sinus blood flow increased to a greater extent in the transplanted group (75 +/- 35% vs 48 +/- 31%, P < 0.05) and myocardial oxygen consumption also tended to increase more in these patients (78 +/- 42% vs 48 +/- 34%, NS). Myocardial adrenaline extraction was greatly reduced in the transplant patients (-6 +/- 25% vs 64 +/- 18%, P < 0.001), while forearm adrenaline extraction was similar in the two groups (41 +/- 22% vs 40 +/- 23%, NS). Cardiac noradrenaline overflow tended to be lower in the transplanted group (12 +/- 62 vs 48 +/- 43 pmol.min-1, NS). There was a wide range of noradrenaline overflow values (-64 to 147 pmol.min-1) and definite high values in three patients. Cardiac noradrenaline overflow was not correlated to heart rate responsiveness to adrenaline. We conclude that patients with cardiac transplantation respond to adrenaline with exaggerated increases in heart rate and thus in cardiac output. High values of cardiac noradrenaline overflow are seen in some transplant recipients and may suggest reinnervation. Signs of reinnervation are not associated with consistently lower heart rate responses to beta-adrenergic stimulation. PMID- 8472711 TI - Occurrence of angina pectoris prior to acute myocardial infarction and its relation to prognosis. AB - In 917 patients with acute myocardial infarction (AMI) we evaluated the impact of previous angina pectoris on the prognosis. Thirty-four percent of the patients had chronic angina prior to AMI, and 22% had angina pectoris of short duration. Patients with chronic angina pectoris differed from the remaining patients having a more frequent previous history of AMI, diabetes mellitus, hypertension, and congestive heart failure. They less frequently developed a Q-wave AMI, and had smaller infarcts according to maximum serum-enzyme activity as compared with the remaining patients. They had a higher one-year mortality rate (36%) as compared with those having angina pectoris of short duration (22%), and those with no angina pectoris (26%). Their reinfarction rate was also higher (26%) as compared with that in the other two groups (15% and 9% respectively). In a multivariate analysis considering age, sex, clinical history, initial symptoms, initial electrocardiogram and estimated infarct size, previous chronic angina pectoris was not an independent risk factor for death, but was independently associated with the risk of reinfarction (P < 0.001). Among patients with a history of angina pectoris the outcome was related to medication prior to onset of AMI and at discharge from hospital. Patients in whom beta-blockers were prescribed at discharge had a one-year mortality of 13% as compared with 30% in the remaining patients (P < 0.001). PMID- 8472713 TI - Seven-year prognostic value of the electrocardiogram at rest and an exercise test in patients admitted for, but without, confirmed myocardial infarction. AB - The seven-year prognosis for cardiac events (non-fatal acute myocardial infarction (AMI) or cardiac death) following discharge was related to an electrocardiogram (ECG) at rest and a symptom-limited exercise test in 217 patients admitted with chest pain without confirmed AMI. The follow-up time was 86-98 months, median 88 months. Although the 7-year prognosis was better than in a comparable group of patients with AMI (P < 0.0001), the frequency of cardiac events was still very high. Patients with negative T waves, ST depression or elevation, intraventricular block or Q waves at rest, ST abnormalities during exercise or both constituted a high-risk group. In patients without these ECG abnormalities the prognosis was significantly better (P << 0.0001). The percentages without cardiac events after 7 years were 53 and 92 respectively. Patients with a low rise in the rate-pressure product indicative of decreased function of the left ventricle and patients who developed angina pectoris during exercise also had a significantly impaired 7-year prognosis. This non-invasive approach to risk stratification identified a group of non-AMI patients with a high risk for cardiac events, and a group comprising more than 50% of the patients with a very low risk. PMID- 8472712 TI - In-hospital experience with multiprogrammable implantable antitachycardia/antifibrillation devices. AB - Multiprogrammable, automatic internal defibrillators with (n = 45) and without (n = 15) antitachycardia pacing features were implanted in 60 consecutive patients with refractory, malignant ventricular tachycardia (VT) (n = 42) or fibrillation (VF) (n = 18). Left ventricular (LV) ejection fraction was reduced to 39% +/- 12% as a result of structural heart disease in 56 patients. The complexity of the systems caused no additional risks to the surgical procedure or postoperative management. VT/VF detection parameters were individually adjusted to the arrhythmia type (detection cycle length 323 +/- 40 ms in patients with VF vs 405 +/- 40 ms for VT patients, P < 0.05) and incidence (longer detection periods if frequent nonsustained VT was also present). Shock energy was reduced in patients with VT as compared to VF (11J vs 24J, P < 0.05). Antitachycardia pacing was activated in 19/28 (68%) patients with well tolerated VT. Signal, telemetry, as detected by the device, combined with programmability allowed the device to be checked for correct decisions (these were inappropriate in four patients in three of whom corrections were non-invasive) prior to discharge. In conclusion, in the automatic tachyarrhythmia control devices we studied, programmability and flexibility appeared to be clinically safe and useful. Prolonged observation periods are required, however, to evaluate the true clinical safety and persistent efficacy of device programmability and flexibility. PMID- 8472714 TI - The mechanism of directional coronary atherectomy. AB - An attempt was made to assess the mechanism of directional coronary atherectomy using different methods of analysis. Quantitative coronary angiography was used as the gold standard to assess the immediate results of atherectomy, and a comparative quantitative analysis of atherectomy and balloon angioplasty was made. To determine whether the post-atherectomy cross-sectional area is close to a circle, we compared the area measurements obtained by edge detection with those obtained by videodensitometry. Finally, the extent of a 'Dotter' effect was established by quantitative angiography following crossing the stenosis with the atherectomy device. For the purpose of this study, the results of the first 113 successful atherectomy procedures were reviewed. In matched lesions, directional atherectomy induced a greater increase in minimal luminal diameter than balloon angioplasty (1.6 mm vs 0.8 mm; P < 0.0001). However, this luminal improvement is due to a substantial 'Dotter' effect induced by the bulky atherectomy device. Following atherectomy, only a slight difference in cross-sectional area measurements between edge detection and videodensitometry (mean difference: 0.28 mm2) was found. Histologic examination of an atherectomized coronary artery showed a near-circular postatherectomy area geometry. In conclusion, directional atherectomy is a very effective device with a substantially better initial result than balloon angioplasty. However, insertion of this bulky device itself causes an important 'Dotter' effect. PMID- 8472715 TI - Electrophysiological characteristics of asymptomatic Wolff-Parkinson-White syndrome. AB - Although most asymptomatic patients with the Wolff-Parkinson-White syndrome have a good prognosis, some die suddenly. Electrophysiological testing may identify patients at possible risk of sudden death. The mechanism of sudden death in these patients is believed to result from ventricular fibrillation due to atrial fibrillation with rapid anterograde conduction over the accessory pathway. Consequently, we performed electrophysiological studies in 40 asymptomatic patients with the Wolff-Parkinson-White syndrome. Certain electrophysiological properties clearly identified these patients: (1) in most patients sustained reciprocating tachycardia could not be induced and this explains the absence of symptoms of regular fast palpitations; (2) the incidence of inducible sustained atrial tachyarrhythmias (30%), of short RR intervals between pre-excited beats (20%) and of risk of sudden death (12.5%) was similar to the incidence in symptomatic patients with the Wolff-Parkinson-White syndrome and reciprocating tachycardia. Because of the ease with which transoesophageal study can be performed we think that the asymptomatic Wolff-Parkinson-White syndrome should be systematically evaluated so as to reassure patients with the benign form that they can lead a normal life and take part in sport and secondly to define the real prognosis of the patients whose characteristics suggests a risk of sudden death. PMID- 8472716 TI - Is sympathetic neural hyperactivity in chronic heart failure affected by heart transplantation? AB - It has been suggested that immunosuppression with cyclosporine induces marked sympathetic neural hyperactivity in heart transplant recipients. In the present study, the resting level of sympathetic nerve activity was investigated with intraneural recording in nine patients with severe chronic heart failure (NYHA class III-IV despite ongoing therapy), in nine heart-transplanted patients with previous heart failure (NYHA class III-IV) receiving standard low-dose triple drug immunosuppression and in six age-matched controls without cardiovascular disease. Compared to the control group, resting sympathetic nerve discharge was markedly increased in heart failure patients (92 +/- 2 vs 60 +/- 6 B/100 b, P < 0.01), sympathetic nerve activity was lower in the majority of heart failure patients after heart transplantation, and mean burst incidence was significantly lower than in the cardiac failure group (70 +/- 7, P < 0.01). The difference between transplanted patients and the control group was not statistically significant. Thus, heart transplant recipients may reduce the augmented central sympathetic drive associated with cardiac failure despite ongoing cyclosporine treatment. PMID- 8472717 TI - Impaired subsidiary pacemaker function in patients with a right bundle branch block created prior to complete catheter ablation of the AV junction. AB - The impact of a right bundle branch block (RBBB), inadvertently created prior to complete ablation of the atrioventricular (AV) junction, on the intrinsic subsidiary pacemaker function was investigated. In 31 patients suffering from intractable supraventricular tachyarrhythmia, catheter ablation of the AV junction was performed using direct current (n = 13) or radiofrequency (n = 18) energy. In 16/31 patients a RBBB was created prior to complete AV ablation. Subsidiary pacemaker function was evaluated after a mean period of 5 months. Following 5 min of ventricular pacing (70 beats.min-1) escape interval and spontaneous heart rate were measured. In patients with a RBBB there was a trend towards a longer escape interval (2979 +/- 2559 vs 1867 +/- 1254 ms, P = ns) and a significantly lower intrinsic heart rate (38 +/- 14 vs 47 +/- 8 beats.min-1, P < 0.05). Pacemaker dependency was only observed among patients with a RBBB (4/16 vs 0/15, P < 0.05). HV intervals were shorter in those energy discharges resulting in a RBBB as compared to those inducing a complete heart block (52 +/- 8 vs 66 +/- 6 ms, P < 0.05). Creation of a RBBB prior to complete ablation of the AV junction results in impaired intrinsic subsidiary pacemaker function; the most proximal catheter position should be carefully sought to minimize the risk of pacemaker dependency. PMID- 8472718 TI - Heart rate and late mortality in cardiac transplant recipients. AB - There are currently 104 patients at this centre who have survived at least 3 months after orthotopic cardiac transplantation. Seven of these long-term survivors have subsequently died and in three cases death was sudden and unexpected. All three of these patients had been noted to have inappropriately high resting heart rates (> 130 b.min-1). The rhythm was sinus tachycardia, supraventricular tachycardia or both intermittently. The heart rates of all 104 long-term survivors were recorded from ECGs taken at routine follow-up visits every 3 months for one year and annually thereafter. The overall mean heart rate was 100 +/- 13.2 b.min-1. Four patients, including the three identified above, had mean heart rates greater than the 95th centile. The mortality rate in this group is 75%. Four deaths have occurred in the remaining 100 patients (P < 0.001). In our series, an inappropriately high resting heart rate due to sinus tachycardia or supraventricular tachycardia in long-term survivors of cardiac transplantation, is an adverse prognostic sign. PMID- 8472720 TI - The effect of verapamil on major events in patients with impaired cardiac function recovering from acute myocardial infarction. The Danish Study Group on Verapamil in Myocardial Infarction. AB - In the Danish Verapamil Infarction Trial II (DAVIT II) intervention with verapamil significantly decreased the first major event rate (i.e. reinfarction or death) in patients recovering from acute myocardial infarction. As calcium channel antagonists might have a detrimental effect in patients with heart failure, the effect of verapamil on major events in patients with and without impaired left ventricular function was analysed. Eight hundred and seventy-eight patients were randomized to verapamil 120 mg t.i.d. and 897 to placebo. Patients were followed up to 18 months. The endpoint was the first major event while on trial medication. In patients treated for heart failure during the acute phase of myocardial infarction, the lowest 18-month event rate was seen in the verapamil group (21.2% vs 22.2%) (absolute numbers: events/patients verapamil 47/291; placebo 60/323) (ns). Similarly, in patients treated with diuretics at randomization, the lowest 18-month event rate was seen in those randomized to verapamil (22.4 vs 24.3%) (absolute numbers: events/patients verapamil 57/349; placebo 76/375 (ns). When patients were subdivided according to New York Heart Association functional classes, verapamil reduced the event rate in all classes, but none of these differences was statistically significant. In patients without heart failure during the acute phase and in patients without diuretic treatment at randomization, treatment with verapamil caused a significant reduction in major events (hazard ratio (95% confidence limits): 0.66 (0.47, 0.92); 0.66 (0.45, 0.96) respectively). Long-term treatment with verapamil after acute myocardial infarction caused a significant reduction in major events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472719 TI - A comparison of nisoldipine and nifedipine, in combination with atenolol, in the management of myocardial ischaemia. AB - The effects of the addition of slow-release nifedipine 20 mg twice daily and nisoldipine 10 mg twice daily to atenolol monotherapy were compared in a double blind placebo-controlled study of 24 patients with chronic stable angina pectoris. Neither nisoldipine nor nifedipine was associated with significant subjective benefit at these doses. Two hours post-dosing, exercise capacity improved after both nisoldipine (duration + 37 s, P < 0.01; time to angina + 67 s, P < 0.01; time to significant ST depression + 60 s, P < 0.01) and nifedipine (duration + 21 s, ns; time to angina + 56 s, P < 0.05; time to significant ST depression + 49 s P < 0.05). However, this improvement was not maintained 12 h post-dosing. Ambulatory monitoring did not demonstrate a significant reduction in the amount of silent or total ischaemia following the addition of either nifedipine or nisoldipine to atenolol monotherapy. There was no significant difference between nifedipine and nisoldipine in any parameter tested. In conclusion, like slow-release nifedipine 20 mg, the effective duration of anti ischaemic action of nisoldipine 10 mg is less than 12 h. Since several patients experienced vasodilatory unwanted effects, more frequent administration rather than larger individual doses may be desirable to achieve a clinical response. PMID- 8472721 TI - The use of propafenone in the treatment of tachyarrhythmias in children. AB - Propafenone was given to 60 children (mean age 4.5 years) with paroxysmal re entrant supraventricular tachycardia (rSVT: 41 cases), postoperative automatic junctional tachycardia (JET: eight cases), automatic atrial tachycardia (AT:four cases), ventricular tachycardia (VT:four cases) and atrial flutter (AF: three cases). In acute cases (29) propafenone was administered intravenously (mean dose 1.3 +/- 0.5 mg.kg-1) chronic oral treatment (mean dose of either 11 +/- 3.3 mg.kg.day-1 or 265 +/- 78 mg.m-2 x day-1) was given to 48 children, in 2-3 divided doses. Overall efficacy was 76% for acute and 69% for chronic treatment, with best results in paroxysmal rSVT. It was effective in 89% acutely of those treated acutely and in 69% of those administered chronically. The efficacy of propafenone in the prevention of rSVT was strictly related to the incidence of attacks before treatment:propafenone was indeed inefficacious in 6/11, 6/14 and 0/12 of patients with daily, weekly and monthly attacks respectively. Side effects were observed in 25% of patients: 6% required suspension of therapy due to pro-arrhythmic effects in one patient on intravenous administration, peripheral neuropathy in one case and hypotension in two postoperative JET patients. In conclusion, its efficacy and limited side effects make propafenone a relatively safe and very useful drug in the treatment of various tachyarrhythmias. However, risk of unpredictable toxic levels requires careful use of the drug especially in the first days of treatment, when a daily monitoring of ECG is strongly recommended. PMID- 8472722 TI - Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. AB - Calcium sensitization increases myocardial contractility by improving energy utilization of the myocardium, without an increase in intracellular concentrations of cyclic adenosine monophosphate. The calcium sensitizer most extensively studied up to now is pimobendan (UD-CG 115 BS). Vasodilatation results primarily from phosphodiesterase III inhibition. Orally administered pimobendan appears rapidly in plasma. A peak concentration is reached 1.5 h after drug intake; elimination from the plasma compartment has a half-life of 1.5 h. First-pass hepatic O-desmethylation of pimobendan produces the active metabolite UD-CG 212; plasma concentration curves of UD-CG 212 are similar to those of pimobendan, with a peak concentration 1-2 h later than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendan produces a dose-dependent and prolonged decrease in pulmonary capillary wedge pressure and an increase in cardiac output. Maintenance doses of pimobendan are well tolerated and may lead to lasting symptomatic improvement in patients with heart failure; open and blinded trials show that exercise tolerance increases. No attenuation of these effects is seen during long-term therapy with pimobendan. Patients in chronic congestive heart failure frequently die suddenly; many inotropic agents increase the incidence of sudden death in these patients. Although proarrhythmia has never been observed with pimobendan, arrhythmia suppression with amiodarone seems prudent in heart failure patients receiving maintenance doses of pimobendan. PMID- 8472723 TI - Left ventricular assistance using a catheter-mounted coaxial flow pump (Hemopump) in a canine model of regional myocardial ischaemia. AB - The global and regional effects of left ventricular circulatory assistance were examined in dogs during acute myocardial infarction using a new coaxial flow device (Hemopump). In 12 dogs the left anterior descending coronary artery was occluded for 4 h and subsequently reperfused for 12 h. In six dogs, left ventricular assistance was started 90 min after coronary artery occlusion and maintained for several hours; six control animals received no circulatory support. Survival rate in the animals receiving mechanical support was 100% vs 0% in the control group. The Hemopump reduced left ventricular stroke work up to 80% and maintained blood flows to the brain, kidneys, liver and intestine throughout the experiment. Infarct size, expressed as a percentage of the left ventricle, however, was not modified (12% in supported animals vs 13% in control dogs). Side effects of the coaxial flow pump were thrombocytopaenia, occurring in all six dogs, and haemolysis, which was demonstrated in one animal. It was concluded that the Hemopump provides effective global and regional circulatory support in a canine model of severe cardiogenic shock. However, the value of left ventricular support to modify infarct size could not be demonstrated in this experimental model. PMID- 8472725 TI - Open heart surgery in Europe 1990. PMID- 8472724 TI - Renovascular hypertension and coronary heart disease complicating essential thrombocythemia. AB - A 36-year-old male was evaluated for treatment-resistant hypertension. A high platelet count 828 x 10(9).l-1, led to the diagnosis of essential thrombocythemia (ET). Aorto-renal angiography revealed critical bilateral renal artery stenosis and coronary angiography showed three-vessel disease. Percutaneous transluminal renal angioplasty was only partially successful. The patient received a 12-week course of busulphan and subsequently the thrombocyte count decreased to 200 x 10(9).l-1. Renal angiography 12 months later showed bilateral regression of the renal artery stenosis with lowering of the blood pressure to normal levels. PMID- 8472727 TI - Carcinoma of the inguinal region arising from endometriosis of the round ligament. Report of a case. AB - The case is reported of a patient with a mixed epithelial tumor, composed mainly of a clear cell and endometrioid carcinoma, arising from a focus of preexisting endometriosis of the round ligament. The tumor was presented as a painful inguinal hernia. PMID- 8472726 TI - The addition of etoposide and ifosfamide to cisplatin as second line therapy in ovarian carcinoma. AB - Forty-five patients with progressive or recurrent ovarian carcinoma received cisplatin, etoposide, and ifosfamide as salvage chemotherapy. The primary purpose of this trial was to evaluate if etoposide and ifosfamide added to cisplatin was effective second line therapy in the 20 patients with progressive or recurrent ovarian cancer after first line cisplatin-based chemotherapy. The overall response in the 20 patients was 20%, all of which were complete responses. However, responses were seen only in patients who had previously responded to first line cisplatin-based chemotherapy and then developed recurrent cancer, whereas none of the patients whose cancer progressed during first line cisplatin based chemotherapy responded. The addition of etoposide and ifosfamide to cisplatin as second line therapy does not potentiate cisplatin in patients demonstrating first line cisplatin resistance and most likely does not contribute to the second line responses in those patients who demonstrated first line cisplatin sensitivity. This combination is also ineffective as third, forth, fifth or sixth line salvage chemotherapy with a response rate of only 8%. PMID- 8472728 TI - Topical acetone for control of life-threatening vaginal hemorrhage from recurrent gynecologic cancer. AB - Two patients with intractable, life-threatening vaginal bleeding from recurrent gynecologic cancer were successfully treated with application of topical acetone or placement of an acetone-soaked pack, with immediate control of hemorrhage and no immediate side effects other than pain. No long-term adverse effects were noted. Acetone application may control vaginal bleeding from recurrent pelvic malignancy, particularly in previously radiated patients who cannot safely be treated with additional radiotherapy or when embolic techniques are not immediately available or practical. PMID- 8472729 TI - Negative second-look laparotomy does not preclude recurrence in stage I ovarian carcinoma of any histological variety. AB - Between January 1980 and June 1991, 56 patients with Stage I ovarian carcinoma of different histological varieties were submitted to a second-look laparotomy (SLL) at the University Clinic (Hospital de Cruces) of Bilbao, Spain. The operation was performed upon all patients one year after initial surgery, after completion of adjuvant chemotherapy, or after one year of observation in those cases that were not treated postoperatively. The SLL was negative in 55 of cases and positive in one. The median follow-up after SLL was 59 months. Of the 55 negative cases, four (7.3%) have had a recurrence of their tumor during their long-term follow-up. Three had epithelial tumors and had received complete postoperative chemotherapy, and the fourth was a dysgerminoma. The three patients with epithelial tumors have died under second-line chemotherapy, whereas the dysgerminoma patient is responding well to rescue polychemotherapy. In view of these results, it is useless and probably unethical to perform second-look laparotomy in Stage I ovarian carcinoma if the initial staging was properly performed. PMID- 8472731 TI - Response of "benign" metastasizing leiomyoma to progestin withdrawal. Case report. AB - We report a rare case of a benign metastasizing leiomyoma in which progestin therapy permitted or promoted pulmonary metastases, but progestin withdrawal induced a marked tumor regression. The significance of these observations is discussed relative to the estrogen and progesterone receptor positivity of this patient's tumor. PMID- 8472730 TI - Primary carcinoid tumor of the ovary. A case report. AB - The clinicopathologic features of a patient with primary carcinoid tumor of the ovary who presented with the signs of cardiac failure are described. The patient underwent total abdominal hysterectomy + bilateral salpingo-oophorectomy + omentectomy + bilateral pelvic lymphadenectomy + appendectomy; and she is alive with no evidence of recurrent disease one year after surgery. PMID- 8472732 TI - Serous papillary adenocarcinoma of the endometrium. A unique entity with a grave prognosis. Case report and review of the literature. AB - A case of Papillary Serous Adenocarcinoma of the endometrium is described. This unique variant of endometrial carcinoma was described initially only 10 years ago. The tumor has distinct pathological characteristics and a very grave prognosis. The importance of identifying this unique tumor type is related to appropriate treatment as well as to correct statistical analysis of endometrial carcinoma. PMID- 8472733 TI - Endometrioid carcinoma of the ovary. Retrospective study. AB - From 1985 to 1991, 9 patients with endometrioid carcinoma of the ovary were treated and followed at the University of Ancona, Department of Gynecology and Obstetrics. Four patients (44.4%) had Stage I disease, 1 (11.1%) Stage II, 1 (11.1%) Stage III and 3 (33.3%) Stage IV. Six patients (66.6%) had grade 2 of the disease and 3 (33.3%) grade 3. Two of the patients (22.2%) had synchronous endometrial carcinoma while 3 had histologic evidence of endometriosis at the time of presentation. All the patients received treatment of combination of surgery, polychemotherapy, hormone and/or immunotherapy. The overall survival rate after a median follow up of 26.6 months was 66.6%. A high survival (100%) was observed for patients with associated endometriosis. PMID- 8472734 TI - Vulvar carcinoma at Srinagarind Hospital, Khon Kaen, Thailand. AB - From 1978 to 1991, 69 cases of primary carcinoma of the vulva were diagnosed and treated at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. The average age was 56 years at the time of diagnosis. Five patients (7.2%) were in FIGO Stage I, 25 (36.2%) Stage II, 28 (40.6%) Stage III and 11 (15.9%) Stage IV. Histologically, 60 cases were squamous cell carcinoma, large cell non-keratinizing type, 2 (2.9%) of squamous cell carcinoma, large cell keratinizing type, 2 (2.9%) of adenocarcinoma, 1 (1.4%) of basal cell carcinoma and 1 (1.4%) of malignant melanoma. Radical vulvectomy with inguino-femoral lymphadenectomy were performed in 42 patients. The rest were rejected or unsuitable for surgery. The actuarial 5 and 10-year survival rate for 61 patients followed up 1 to 14 years was 66.0%. The 5-year survival rate for operable cases was 88.5% but for unoperable cases it was only 22.0%. The authors still confirm surgery as the primary treatment of choice for this rare malignancy. PMID- 8472735 TI - Prevention of postoperative thromboembolism in gynaecological malignancy. AB - A prospective randomized clinical trial compared the efficacy of low doses of heparin (LDH) and heparin plus dihydroergotamine mesylate (HDHE) in the prevention of thromboembolism in gynaecological patients with malignancy undergoing major surgery. One hundred and fifty-five patients, with a mean age 54.5 years were allocated to receive 5,000 IU unfractionated heparin or 5,000 IU unfractionated heparin +0.5 mg dihydroergotamine mesylate twice daily. Treatment was begun 2 hours preoperatively and continued until discharge (12 +/- 7 days). The incidence of thromboembolism determined by radiolabelled fibrinogen and lung perfusion scanning was 21.3% in LDH group and 22.7% in HDHE group. There were no statistically significant differences between the two groups (p > 0.1). The observed haemorrhagic rate was 1.9% in both groups. HDHE prevention was more expensive but without significant advantage over LDH. During two months after surgery 4 patients (5%) in the LDH group and 1 patient (1.8%) in the HDHE group developed deep vein thrombosis. PMID- 8472736 TI - Risk factors in vulvar carcinoma recurrences. AB - 18 patients with invasive vulvar carcinoma treated by radical vulvectomy and bilateral groin lymphadenectomy have been evaluated. An 18% of local and 22% of pelvic or distant recurrences occurred. The local recurrences had favorable prognosis, whereas the pelvic or distant recurrences a worse prognosis. The staging, the tumour size, the nodes involvement, the stromal infiltration and the lymphoplasmacytic infiltration, as prognostic factors, have been evaluated. All these factors, except the tumour size, influenced the pelvic or distant recurrences. The pelvic or distant recurrences were contemporaneously associated with mild phlogistic infiltration and depth of invasion > 5 mm. PMID- 8472737 TI - Antiarrhythmic effects of bisaramil in canine models of ventricular arrhythmia. AB - The antiarrhythmic effects of bisaramil were examined in canine models of digitalis-, adrenaline- and two-stage coronary ligation- induced arrhythmia. Bisaramil (0.3-1.5 mg/kg i.v.) suppressed all the arrhythmias. The antiarrhythmic plasma concentration (IC50) for arrhythmias induced by digitalis, adrenaline, and 24 h two-stage coronary ligation were 0.11, 0.81, and 0.75 micrograms/ml, respectively. Bisaramil is a potent class I agent, judging from its low antiarrhythmic plasma concentrations. Oral bisaramil (10 mg/kg) also suppressed 24-h coronary ligation-induced arrhythmia. These results indicate that bisaramil may be a useful drug for the treatment of various clinical ventricular arrhythmias. PMID- 8472738 TI - Effects of central vasopressin administration to infant rats. AB - The neurohypophyseal peptide hormone arginine-vasopressin functions as a neuropeptide in several brain areas in addition to its role as a posterior pituitary hormone. Several studies indicate that arginine-vasopressin and arginine-vasopressin receptors appear early in the infant rat brain. To determine if arginine-vasopressin receptors in the infant were responsive to exogenous peptides, we compared the behavioral effects of central or peripheral administration of arginine-vasopressin, arginine vasotocin, the oxytocin precursor oxytocin-Gly-Lys-Arg, and arginine-vasopressin receptor antagonists in socially isolated rat pups. Central administration of arginine-vasopressin decreased the number of rat pup ultrasonic vocalizations, reduced locomotor activity and decreased the latency to express a response to negative geotaxis. Temperature was also reduced at all doses tested. Co-administration of arginine vasopressin and receptor antagonists suggested that changes in vocal behavior were mediated by the V1 receptor subtype. Changes in core temperature appeared to be mediated by a V2 receptor subtype. Peripheral arginine-vasopressin administration increased calling and decreased core body temperature. Neither effect was blocked by central receptor antagonist administration. The results are consistent with the hypothesis that arginine-vasopressin receptors in the infant rat brain are functional. PMID- 8472739 TI - Identification of a specific receptor for interleukin-1 in vascular smooth muscle cells: regulation by interleukin-1 and interleukin-6. AB - A fluorescently labeled ligand was utilized to establish the existence of an interleukin-1 (IL-1) receptor in vascular smooth muscle. The binding of the phycoerythrin-labeled IL-1 beta to the murine T cell line, EL-4, was examined as a positive control. The phycoerythrin-labeled IL-1 beta identified a specific IL 1 receptor in the EL-4 cells. Vascular smooth muscle cells were also positively stained by the fluorescent ligand. The binding of phycoerythrin-labeled IL-1 beta to these cells was saturable and reversed by 100-fold excess unlabeled IL-1 beta. Incubation of the vascular smooth muscle cells with IL-1 beta (25 ng/ml) or IL-6 (250 ng/ml) for 18 h increased and decreased, respectively, the percentage of cells positively stained by phycoerythrin-labeled IL-1 beta which suggests these cytokines regulate IL-1 receptor expression in these cells. These data indicate a specific receptor for IL-1 exists in vascular smooth muscle cells. PMID- 8472740 TI - The role of atrial natriuretic peptide in the diuretic effect of Ca2+ entry blockers. AB - The effect of three calcium entry blockers--verapamil, nifedipine and felodipine- on diuresis, natriuresis, the renin-aldosterone axis, and atrial natriuretic peptide (ANP) levels was studied in 30 previously untreated patients with mild to moderate essential hypertension. All three blockers produced significant antihypertensive effects after 2 and after 24 h. Heart rate tended to decrease, but did not change significantly after verapamil, but increased significantly 1-2 h after nifedipine and felodipine. Plasma renin activity (PRA) did not change significantly with any treatment, and plasma aldosterone decreased with all three agents. ANP levels did not change significantly after verapamil, but increased significantly after nifedipine and felodipine. There was a significant positive correlation between the maximal change in ANP level and urinary sodium after nifedipine and felodipine. The increase in urinary sodium after verapamil was not significant. The role of the direct renal effect of calcium entry blockers in their persistent natriuretic action is discussed, as well as their short-term enhancement of ANP levels, which may account for the initial diuretic and natriuretic effects seen with this class of dihydropiridines. PMID- 8472741 TI - Effect of ovarian steroids and diethylstilbestrol on the contractile responses of the human myometrium and intramyometrial arteries. AB - Estriol, estradiol, progesterone and diethylstilbestrol in the concentration range of 0.2-40 microM inhibited the spontaneous contractions of the myometrium in a dose-dependent manner but the differences in IC50 values obtained with different hormones were not statistically significant. All these hormones caused a concentration-dependent inhibition of the K(+)-induced contraction. The IC50 values were lowest for diethylstilbestrol and highest for estriol. Vasopressin at concentrations of 1.5 x 10(-6) - 1.8 x 10(-3) U/ml stimulated myometrial contractions. These responses were also inhibited by ovarian steroids and diethylstilbestrol. The IC50 values for estriol and progesterone were significantly higher than for estradiol or diethylstilbestrol. The values for estriol and progesterone did not differ significantly. In the uterine arteries, which lacked spontaneous activity, ovarian steroids and diethylstilbestrol inhibited contractions induced by K+ depolarization. As with myometrium, the lowest effect was observed with estriol and the highest with diethylstilbestrol. A dose-dependent inhibition by all four hormones (0.2-40 microM) of vasopressin induced contractile responses of the uterine arteries was observed. With the lowest concentration of progesterone, however, the arterial response to vasopressin was enhanced. The increases by progesterone (0.02 and 0.2 microM) of responses induced by vasopressin were statistically significant (P < 0.05). The present data strongly suggest that, in human myometrium and uterine arteries, ovarian steroids and diethylstilbestrol cause a more pronounced inhibition of receptor-mediated than of voltage-dependent Ca2+ channels. The increase by a very low (physiological) concentration of progesterone of vasopressin-induced responses in both myometrium and arteries may be of significance in the pathophysiology of dysmenorrhea. PMID- 8472742 TI - Haloperidol and clozapine increase intraneuronal dopamine metabolism, but not gamma-butyrolactone-resistant dopamine release. AB - In a previous study, two coexisting mechanisms of dopamine release were identified in dopamine neuron terminals. One can be blocked with gamma butyrolactone, suggesting it is impulse flow-dependent, while the other one cannot and is apparently impulse flow-independent. The goal of this study was to further characterize the gamma-butyrolactone-resistant mechanism and its relation to dopamine metabolism. Following acute and chronic haloperidol or clozapine treatment, gamma-butyrolactone was given to block dopamine neuronal impulse flow. In all groups, 3-methoxytyramine levels after monoamine oxidase inhibition with pargyline (an index of dopamine release) were measured in the frontal cortex, nucleus accumbens and striatum. Regional steady-state levels of dopamine, 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also measured in the rats treated acutely with neuroleptics. In all three regions, gamma butyrolactone reduced the 3-methoxytyramine levels by over 50% after chronic neuroleptic treatment. This indicates that dopamine release from the terminals is primarily impulse flow-dependent during chronic neuroleptic treatment, both in the dopamine neurons which do undergo depolarization block, and in those that do not. No neuroleptic effect on the gamma-butyrolactone-resistant dopamine release was observed, while DOPAC and HVA were markedly elevated by the acute treatment, suggesting a predominant production of these metabolites from unreleased dopamine. PMID- 8472743 TI - Behavioral effects of chronic cocaine treatment in the week-old rat pup. AB - Chronic treatment of adult animals with cocaine results in sensitization to some behavioral effects and tolerance to others but there are few reports on the effects of chronic stimulants during early development. The present experiments assessed the development of cocaine-induced alterations in locomotor activity and separation induced ultrasonic vocalization, a fundamental behavior of infant rats. The first study demonstrated a dose dependent suppression of ultrasounds in naive pups at 7 days of age that lasted at least 60 min and that was accompanied by a dose dependent increase in locomotion. To assess chronic effects, pups were injected with cocaine (5.0-30.0 mg/kg) twice daily from ages 1 to 7 days and then tested at 7, 8 and 10 days of age for vocalization in response to isolation from the dam and littermates. There were minimal effects on baseline levels of crying, but following chronic treatment with cocaine, pups showed generally higher levels of ultrasounds when tested with an acute challenge of cocaine at 7 and 8 days of age. In chronically treated pups locomotor activity was increased during baseline tests. At 10 days of age, 3 days after the last treatment with cocaine, in the highest dose treatment condition, there was an exaggerated reduction of ultrasounds when tested with a littermate. The results demonstrate that chronic exposure to cocaine during early development disrupts the normal regulation of a developmentally important socially mediated behavior. PMID- 8472744 TI - Isradipine attenuates the ischemia-induced release of dopamine in the striatum of the rat. AB - We examined the effect of isradipine, a blocker of L-type voltage-sensitive Ca2+ channels (VSCCs), on the ischemia-induced release of dopamine in the rat striatum. Perfusion of 200 micrograms/ml isradipine in the striatum did not alter extracellular dopamine concentrations monitored by microdialysis. However, a marked increase (145-fold) in dopamine level during forebrain ischemia, developed by bilateral carotid artery occlusion, was attenuated significantly by 37% by isradipine whereas the intensity of ischemia, monitored by striatal blood flow, was unchanged. These results suggest that isradipine attenuates the ischemia induced release of dopamine via blockade of L-type VSCCs on dopaminergic neurons. PMID- 8472745 TI - High- and low-affinity states of dopamine D1 receptors in schizophrenia. AB - Using SKF-38393/[3H]SCH-23390 dopamine D1 receptor agonist/antagonist competition binding technique, we showed that schizophrenics distinguished from the neuro psychiatric and normal controls by exhibiting a significant increase in the density of the low-affinity state, and a concomitant enhancement in the binding affinity of the high-affinity state of D1 dopamine receptors in caudate nucleus. The results suggest that perturbation in dynamic equilibrium of high- and low affinity states of D1 receptors underlies the pathogenesis of schizophrenia. PMID- 8472746 TI - Effects of a novel thyrotropin-releasing hormone analogue, JTP-2942, on extracellular acetylcholine and choline levels in the rat frontal cortex and hippocampus. AB - The effects of a novel thyrotropin-releasing hormone (TRH) analogue, N alpha [(1S,2R)-2-methyl-4-oxocyclopentanecarbonyl]-L-histidyl-L-pr olinamide (JTP-2942) on acetylcholine (ACh) release and on the extracellular choline level were investigated in rat frontal cortex and hippocampus by microdialysis, and were compared with effects of TRH. JTP-2942 (0.3 mg/kg i.p.) produced a marked (> 300%) and persistent increase of ACh release in both the frontal cortex and hippocampus, while TRH (3 mg/kg i.p.) caused a significant but transient increase of ACh to about 200% in the frontal cortex. Both drugs significantly decreased the choline levels in both brain regions. Investigation of the effects of JTP 2942 (0.001-1 mM) and TRH (1 and 10 mM) on ACh release and choline levels when perfused through the dialysis probe revealed that JTP-2942 had a greater effect than TRH in both the frontal cortex and the hippocampus. The action of JTP-2942 was about 1000-fold more potent than that of TRH in both brain regions. Oral administration of JTP-2942 at a dose of 10 mg/kg markedly and persistently increased the release of ACh and at doses of 1-10 mg/kg decreased the extracellular choline level in the frontal cortex and hippocampus. These results also suggest that JTP-2942 has some selectivity for the hippocampus compared to the frontal cortex after both systemic administration and local injection. The increase of ACh release caused by JTP-2942 was completely antagonized by perfusion with tetrodotoxin (TTX, 1 microM), suggesting that the action of JTP 2942 on cholinergic neurons was mediated via neuronal activity. PMID- 8472747 TI - Autoradiographic studies of RP 62203, a potent 5-HT2 receptor antagonist. Pharmacological characterization of [3H]RP 62203 binding in the rat brain. AB - The binding properties and localization of [3H]RP 62203, a novel ligand for 5-HT2 receptors, were investigated on rat brain sections. The specific binding of this 5-HT2 receptor antagonist was reversible and could be displaced by ritanserin (1 microM). Saturation experiments revealed a single class of binding sites with a KD of 0.128 +/- 0.018 nM and a Bmax of 1.67 +/- 0.06 pmol/mg protein. Pharmacological specificity was demonstrated by the potency order of displacing agents: RP 62203 > ritanserin > spiperone > methysergide > mianserin > pipamperone > cinanserin > 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Quantitative autoradiography showed a heterogeneous distribution of [3H]RP 62203 binding sites, with the highest densities in the frontal, parietal and auditory cortices (layer IV), claustrum and olfactory bulb. Binding densities in the occipital cortex, caudate putamen and thalamic nuclei were moderate, whereas the hippocampus and substantia nigra displayed a very low density of binding sites. The cerebellar cortex appeared almost devoid of [3H]RP 62203 binding sites. The anatomical distribution of binding sites demonstrated that [3H]RP 62203 essentially bound only to rat brain regions known to contain 5-HT2 receptors. This ligand could thus be a useful tool to visualize 5-HT2 receptors. PMID- 8472748 TI - Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs. AB - In anesthetized and ventilated guinea-pigs, intravenous injections of endothelin (ET)-1 (0.5 nmol/kg), ET-3 (0.5 nmol/kg), and [Ala1,3,11,15]ET-1 (20 nmol/kg), an ETB-selective receptor agonist, induced bronchoconstrictor and transient vasoconstrictor responses. Only the ET-1-induced transient vasoconstriction was followed by a secondary sustained pressor response. The ETA-selective receptor antagonist, BQ-123 (1 mg/kg i.v.), attenuated only the sustained pressor response. These results indicate that the bronchoconstrictor and transient vasoconstrictor responses to endothelins in guinea-pigs are mediated by ETB receptors, whilst the sustained pressor response is mediated by ETA receptors. The thromboxane A2 receptor antagonist, L-670,596 (0.5 mg/kg, i.v.) and a high dose of BQ-123 (30 mg/kg i.v.) abolished the bronchoconstriction only without affecting the transient pressor response to endothelin isopeptides. These results suggest that the ETB-mediated bronchoconstriction depends on thromboxane A2 formation. The different sensitivity of these ETB-mediated transient responses to BQ-123 suggests the possible existence of distinct ETB receptor subtypes. PMID- 8472749 TI - Protection of infarcted, chronically reperfused hearts by an alpha-tocopherol analogue. AB - Free radicals may cause part of the irreversible injury which occurs during myocardial infarction and reperfusion. In the present study MDL 73404, a hydrophilic, cardioselective, free radical scavenger analogue of alpha tocopherol, was evaluated for its effects on infarct size as well as on indicators of reperfusion injury. A pentobarbitone-anaesthetised rat model of coronary artery ligation (60 min; followed by 8 days of reperfusion) was used. Intravenous infusion of MDL 73404 (3 mg/kg per h) began 10 min before occlusion until 30 min after the onset of reperfusion. MDL 73404 reduced (P < 0.02) the elevated serum levels of thiobarbituric acid reactive substances and plasma levels of creatine phosphokinase (P < 0.01). An increase in cardiac output and heart rate together with a decrease (P < 0.01) in infarct size was evident in rats that had received MDL 73404, 8 days previously. Isolated infarcted hearts obtained from rats after 8 days of reperfusion had greater (P < 0.01) + dP/dt max, -dP/dt max, left ventricular systolic pressure and coronary flow after MDL 73404 compared to saline-treated controls. Infusion of [14C]MDL 73404, during the time of occlusion resulted in a concentration of 14.5 +/- 2.2 mg eq/g in the non ischaemic ventricular tissue and a concentration of 3.0 +/- 0.4 mg eq/g in the area at risk. After infusion for the 30 min of reperfusion, 6.4 +/- 0.2 mg eq/g was detected in the non-ischaemic ventricular tissue but only 3.1 +/- 0.5 mg eq/g in the area at risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472750 TI - Nitric oxide inhalation attenuates pulmonary hypertension and improves gas exchange in endotoxin shock. AB - Nitric oxide (10 ppm) inhaled by pigs before or during endotoxin shock induced by an infusion of E. coli lipopolysaccharide. Nitric oxide inhalation selectively attenuated pulmonary hypertension during endotoxin infusion without influencing mean arterial blood pressure and cardiac output. Upon cessation of nitric oxide inhalation, pulmonary artery pressure rapidly increased to levels seen in endotoxin-treated controls. The oxygenation and pH of arterial blood were significantly higher in the animals receiving nitric oxide. A marked increase in arterial plasma noradrenaline and neuropeptide Y was seen in endotoxin-treated control pigs while in the nitric oxide-treated pigs this increase was markedly reduced. The increase in arterial plasma endothelin-1 was not influenced by nitric oxide inhalation. Infusion of L-arginine (substrate for nitric oxide synthesis) also attenuated the pulmonary hypertension but was not selective for the pulmonary vasculature. L-Nitro-arginine (a nitric oxide synthesis inhibitor) initiated a rapid but brief elevation of arterial blood pressure and of pulmonary artery pressure as well as a reduction in cardiac output. Nitric oxide inhalation selectively reduces pulmonary hypertension in porcine endotoxin shock and improves arterial oxygenation and pH with a marked attenuation of sympathetic activation. PMID- 8472751 TI - MK-801 is neuroprotective but does not improve survival in severe forebrain ischemia. AB - The effects of MK-801 on postischemic recovery, survival and neuronal preservation in the cortex, hippocampus and striatum were studied in Mongolian gerbils. The drug was administered 30 min prior to 20 of min forebrain ischemia induced by bilateral ligation of the carotids. Neurological recovery and survival were monitored for 7 days. At the end of the monitoring period neuronal damage was analyzed in the brains of the survivors in both groups. Treatment with MK-801 did not improve either neurological recovery or end-point survival. However, significant (P < 0.01) neuronal protection was observed in the hippocampi and striata of the drug treated animals while cortical neurons were not significantly protected. These findings demonstrate that protection against ischemic neuronal damage can be observed without concomitant improvement in either postischemic neurological recovery or survival. Protection of selectively vulnerable brain regions, often used as the predictor of the therapeutic potential of an agent, does not appear to correlate well with postischemic survival in this animal model of ischemia. PMID- 8472752 TI - Characterization of 5-HT receptors in simian isolated gastroepiploic artery. AB - The vascular responses of simian gastroepiploic arteries to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT, a selective 5-HT1-like receptor agonist), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a selective 5-HT1A receptor agonist), m-trifluoromethylphenylpiperazine (TFMPP, a selective 5-HT1B receptor agonist), noradrenaline and KCl were examined in isolated, cannulated and perfused preparations. 5-HT induced dose-dependent vasoconstrictions more potently than noradrenaline did. The rank order of potency was 5-HT > noradrenaline > 5-CT >> 8-OH-DPAT = TFMPP. 5-HT- and 5-CT-induced vasoconstrictions were not significantly changed by endothelial denudation, although acetylcholine-induced vasodilatations were abolished. 5-HT-induced vasoconstrictions were depressed by phentolamine (an alpha-adrenoceptor antagonist), diltiazem (a calcium ion channel inhibitor), methysergide (a 5HT1- and 5HT2-receptor antagonist) and ketanserin (a selective 5-HT2 receptor antagonist). Noradrenaline-induced vasoconstrictions were readily inhibited by phentolamine and ketanserin. 5-CT-, 8-OH-DPAT- and TFMPP-induced vasoconstrictions were inhibited by both methysergide and ketanserin. KCl-induced vasoconstrictions were blocked by diltiazem. From these results, we conclude that (1) the simian gastroepiploic artery contains 5-HT receptors, (2) 5-HT1-like and 5-HT2 receptors are involved in the vasoconstriction of the simian gastroepiploic artery, and (3) the vasoconstriction is at least partially related to the activation of calcium ion channels. PMID- 8472753 TI - 5-HT3 receptors augment neuronal, cholinergic contractions in guinea pig trachea. AB - Serotonin (5-HT) and the selective 5-HT3 receptor agonist, 2-methyl-5 hydroxytryptamine enhanced electrical field stimulated contractions of the isolated guinea pig trachea. 5-HT (EC50 = 3.5 microM) was twice as potent as 2 methyl-5-hydroxytryptamine (EC50 = 7.4 microM). The effects of 5-HT and 2-methyl 5-hydroxytryptamine were antagonized by the selective 5-HT3 receptor antagonist; zacopride (apparent pA2 = 7.60 against 2-methyl-5-hydroxytryptamine). 2-Methyl-5 hydroxytryptamine (10 microM) had no effect on contractile responses to exogenous acetylcholine. Furthermore, the increase in electrical field stimulated contraction by 2-methyl-5-hydroxytryptamine was unchanged by hexamethonium (100 microM) but contractions were blocked by atropine (1 microM). These results suggest that excitatory 5-HT3 receptors exist on postganglionic cholinergic nerves in the isolated guinea pig trachea. PMID- 8472754 TI - The hydrophilic spin trap, 5,5-dimethyl-1-pyrroline-1-oxide, does not protect the rat heart from reperfusion injury. AB - The role and site of free radical generation in myocardial ischemia/reperfusion injury were investigated using the hydrophilic spin trapping agent, 5,5-dimethyl 1-pyrroline-1-oxide (DMPO). DMPO (40 mM) proved ineffective in preserving the contractile performance and energy metabolism of Langendorff-perfused rat hearts following ischemia and reperfusion. This result, which is in contrast with the cardioprotection observed with hydrophobic spin traps, suggests that free radicals are generated intracellularly under these conditions. PMID- 8472755 TI - Contractile effects caused by thaliporphine in the guinea-pig ileum. AB - The intestinal effects of thaliporphine, a potent vasoconstrictor, were studied using the isolated guinea-pig ileum. Thaliporphine (0.1-100 microM) caused contraction in a concentration-dependent manner. The contraction was not affected by pretreatment of the ileum with tetrodotoxin, phentolamine, prazosin, propranolol, naloxone, atropine, diphenhydramine, methysergide, indomethacin or staurosporine. However, the contraction was inhibited markedly by nifedipine and verapamil. These results suggest that thaliporphine causes contraction of intestinal smooth muscle by a direct effect on muscle mediated by an increased Ca2+ influx through voltage-dependent Ca2+ channels. PMID- 8472756 TI - The C-terminal neurotensin-(8-13) fragment potently modulates rat neostriatal dopamine D2 receptors. AB - The effects of neurotensin fragments and of neurotensin itself on the characteristics of neostriatal dopamine D2 agonist binding were studied in competition experiments with dopamine using the D2 antagonist, [3H]raclopride. The biologically active neurotensin-(8-13) fragment, but not the inactive neurotensin-(1-7) fragment, caused a concentration-related increase in the KH and KL values of dopamine with a maximal increase by 110 and 97%, respectively, at 1 nM, while neurotensin-(1-13) only induced such changes at 10 nM. In view of the higher potency and the increased ability of neurotensin-(8-13) versus neurotensin (1-13) to reduce the affinities of the high- and low-affinity states of the neostriatal D2 receptors, the C-terminal neurotensin fragments may be among the endogenous ligands of the neostriatal neurotensin receptors. PMID- 8472757 TI - Nitric oxide from polymorphonuclear leukocytes modulates red blood cell deformability in vitro. AB - We confirmed that iloprost is very potent in preserving the deformability of rabbit red blood cells (RBC). Incubation of RBC with a small number (up to 1.2 x 10(6) cells/ml) of polymorphonuclear leukocytes (PMNs) caused a gradual decline in RBC deformability. The addition of PMNs up to 2.8 x 10(6) cells/ml increased RBC deformability but, at higher concentrations, both in the presence and absence of a neutrophil activating cytokine (interleukin-8; IL-8), PMNs reduced the deformability of RBCs. In the presence of a small number of PMNs, the deformability of RBC was increased by nitric oxide (NO) donors, such as sydnonimine (SIN-1) or sodium nitroprusside, and reduced by the NO synthase inhibitor, NG-monomethyl-L-arginine. We suggest that the deformability of RBC is modulated by PMNs via the release of NO and that the NO concentration is of critical importance in this modulatory mechanism. NO seems to preserve or enhance RBC deformability within a certain range of concentrations, but these effects are reversed or eliminated at both too low and too high concentrations. PMID- 8472758 TI - Effects of Ca2+ channel antagonists in guinea-pig normal and skinned gall bladder. AB - CaCl2 (0.01-50 mM, in K(+)-depolarized tissues), KCl (0.1-100 mM) and acetylcholine (1 nM-10 mM) produced concentration-dependent contractions of guinea-pig isolated gall bladder. Nifedipine (1-100 microM), verapamil (1-100 microM), diltiazem (1-100 microM), cinnarizine (1-100 microM), and flunarizine (1 100 microM) each produced a concentration-related inhibition of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (50 mM)-induced contraction of depolarized gall bladder, was diltiazem (0.25 microM) > or = verapamil (0.8 microM) approximately nifedipine (1.2 microM) >> cinnarizine (25 microM) approximately flunarizine (80 microM). Verapamil and diltiazem depressed KCl induced contraction with an effectiveness and potency similar to those displayed against CaCl2 but nifedipine, cinnarizine and flunarizine were less effective against contractions in response to KCl compared to CaCl2. Verapamil and diltiazem, but not the other Ca2+ channel antagonists tested, had a specific inhibitory effect on the contractions due to KCl when compared to acetylcholine induced contractions. Cinnarizine (10-100 microM) and flunarizine (10-100 microM), but not the other antagonists tested, depressed Ca2+ (20 microM)-evoked contraction of skinned guinea-pig gall bladder preparations. It is concluded that distinct differences exist between the Ca2+ channel antagonists examined. The action of nifedipine, verapamil and diltiazem is restricted to the plasmalemma whereas cinnarizine and flunarizine also act on the intracellular contractile apparatus. PMID- 8472759 TI - Working memory deficits induced by intrahippocampal administration of 8-OH-DPAT, a 5-HT1A receptor agonist, in the rat. AB - In a test of working memory using a three-panel runway task, the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at 1.0 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel gates at four choice points), but it had no effect on errors in a test of reference memory. Intrahippocampal injection of 8 OH-DPAT at 10 micrograms/side also significantly increased the number of working memory errors, without affecting that of reference memory errors. The effect of intrahippocampal 8-OH-DPAT (10 micrograms/side) on working memory was blocked by the 5-HT1A receptor antagonist, (-)-propranolol, at 5 mg/kg i.p. These results suggest that activation of hippocampal 5-HT1A receptors impairs working memory, but does not affect retention of reference memory. PMID- 8472760 TI - Membrane activity of class III antiarrhythmic compounds; a comparison between ibutilide, d-sotalol, E-4031, sematilide and dofetilide. AB - This study compares the membrane activity of ibutilide, d-sotalol, sematilide, E 4031 and dofetilide on single ventricular cells under identical experimental conditions. We found that ibutilide and dofetilide produced a 'bell-shaped' concentration-dependent effect on action potential duration. Ionic current measurement showed that ibutilide, at 10(-8) M, increased a late inward current; the other compounds had either no effect or decreased it. Moreover, only ibutilide, at a high concentration of 10(-5) M, increased an outward current, as oppose to a uniform depression of IK by d-sotalol, sematilide, E-4031 and dofetilide, and the depression of IK by the latter compounds could be reversed by 10(-5) M ibutilide. Finally, low concentration of ibutilide could further prolong the action potential duration that had already been prolonged by a K+ channel blocker, but a high concentration of ibutilide did just the opposite by reversing the prolongation caused by K+ channel blockers. Therefore, action potentials agree well with the ionic current results. Possible mechanistic advantage of ibutilide over K+ channel blockers was discussed. PMID- 8472761 TI - Effect of K+ depolarization, tetrodotoxin, and NMDA receptor inhibition on extracellular adenosine levels in rat striatum. AB - Extracellular adenosine in the striatum of adult male rats was measured by the use of a microdialysis fibre inserted transversely in the striatum. The adenosine concentration in samples of perfusate was determined by HPLC coupled to U.V. detection. The adenosine concentration (corrected for recovery) decreased after implantation of the probe. Two hours later it was 1.83 +/- 0.22 in anaesthetized rats, whereas it was 40% higher in rats in which anaesthesia had been discontinued. Twenty-four hours later the adenosine concentration was 0.124 +/- 0.09 microM; the addition of dipyridamole (100 microM), an adenosine uptake blocker, to the perfusate resulted in a 76% increase in adenosine concentration in the effluent, whereas addition of the adenosine deaminase inhibitor erythro-2 (hydroxy-3-nonyl) adenine (100 microM) caused a 260% increase. The addition of tetrodotoxin (1 microM) was followed by a decrease in basal adenosine concentration and a partial inhibition of the increase in adenosine evoked by K+ depolarization. The increase induced by high K+ was markedly inhibited by the NMDA receptor antagonist D(-)-amino-7-phosphoeptanoic acid (1 mM, D-AP7). These findings indicate that the extracellular adenosine level is influenced by neuronal activity, and that under strong depolarizing conditions the increase in adenosine level involves NMDA receptor activation. PMID- 8472762 TI - Suppressive effect of cycloheximide on behavioral sensitization to methamphetamine in mice. AB - The effect of a protein synthesis inhibitor, cycloheximide, on behavioral sensitization to methamphetamine was investigated in mice. As indicated by the sensitization tests, repeated injection of methamphetamine (2 mg/kg i.p.) at intervals of 3 and 4 days resulted in a progressive augmentation of the locomotor stimulating effect of methamphetamine. This phenomenon, called locomotor sensitization, was attenuated by simultaneous treatment with cycloheximide (120 mg/kg i.p.) at the time of stimulant injection. In contrast, when mice were treated with cycloheximide 4 h after stimulant injection, locomotor activity was progressively augmented in the same way as observed in mice receiving repeated injections of methamphetamine alone. On challenge, it was noted that locomotor activity was significantly higher in mice injected repeatedly with the stimulant alone and in those mice treated with the inhibitor 4 h after the stimulant injection compared to the saline-treated control mice. However, mice that had been simultaneously treated with cycloheximide and methamphetamine showed almost the same locomotor activity as the saline-treated control mice. These observations indicated that the locomotor sensitization to methamphetamine was possibly suppressed by simultaneous treatment with cycloheximide. We then examined the dose- and time-dependent nature of the effect of cycloheximide on locomotor sensitization. The stimulation of locomotion observed after repeated injection of the stimulant at a dose of 1.5 mg/kg was significantly attenuated by simultaneous treatment with 120 or 240 mg/kg of cycloheximide, but not by treatment with 60 mg/kg of the inhibitor. However, all the treatments failed to suppress the development of locomotor sensitization elicited by 3 mg/kg of methamphetamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472763 TI - The role of Escherichia coli O 157 infections in the classical (enteropathic) haemolytic uraemic syndrome: results of a Central European, multicentre study. AB - To assess the importance of infection by Verotoxin (VT) producing Escherichia coli (VTEC) in children with HUS in Central Europe, stool and/or serum samples obtained from 147 patients from 28 paediatric centres were prospectively examined for the presence of VTEC and the kinetics of faecal VT titres (FVT), and for VT neutralization titres and antibodies against E. coli O 157 lipopolysaccharide, respectively. Ninety-two percent of the patients had classic (enteropathic) HUS (E+ HUS). Evidence of VTEC infection was obtained in 86% of them. VTEC/FVT were identified in 55/118 E+ cases (47%). A prominent feature was the frequent isolation of sorbitol-fermenting, VT2-producing E. coli O 157.H-.VT1 (C600/H19) was neutralized by 9%, and VT2 (C600/933W) by 99% of the initial serum samples from E+ patients, compared to 3% (VT1) and 100% (VT2) from age-related controls. Fourfold titre rises against VT1 and/or VT2 were observed in 13/70 (19%), and significantly elevated O 157 LPS IgM and/or IgA antibodies in 106/128 (83%) of the E+ patients. The ubiquitous VT2 neutralizing principle in the serum of HUS patients as of healthy controls warrants further investigations. PMID- 8472764 TI - A longitudinal study of Vero cytotoxin producing Escherichia coli in cattle calves in Sri Lanka. AB - Two cohorts of 10 and 16 calves were followed at weekly or fortnightly intervals from 4-28 and 1-9 weeks respectively to determine whether natural infection by Vero cytotoxin (VT) producing Escherichia coli (VTEC) occurred. Ninety-one of 171 (53%) faecal specimens were VTEC positive and 20-80% of animals at any given time excreted VTEC. Of 104 VTEC strains studied further, 6 different serogroups (O 22.H16; O 25.H5; O 49.H-; O 86.H26; O 88.H25; O 153.H12) and an untypable strain (O? .H21) were identified. All strains belonging to the same serotype had identical profiles of reactivity with DNA probes to toxins VT1 or 2, LTI or II and a probe (CVD419) derived from a plasmid carried by enterohaemorrhagic Escherichia coli O 157.H7. Four of these serotypes were found in the faecal flora of the calves, taken as a group, throughout the 4-month study period. Sixty percent of the strains hybridized with the probe for VT1, 4% with the probe for VT2, and 36% with both probes. Faecal VTEC were significantly associated with overt diarrhoeal illness in animals < 10 weeks of age, but no characteristic profile of markers (serotype or hybridization pattern) in E. coli isolates was associated with diarrhoea. A serological response to VT1 was detected in some animals, but faecal VT1 VTEC excretion persisted in spite of seroconversion. VT1 seroconversion was not associated with diarrhoea. A serological response to VT2 was not detected even in those animals excreting VT2 VTEC in the faeces. PMID- 8472765 TI - Egg-related Salmonella enteritidis, Italy, 1991. AB - In recent years, Salmonella enteritidis has become an increasingly important public health problem in Italy. In some parts of the country, the fraction of total human salmonella isolates accounted for by S. enteritidis has risen from 3 4% in the mid-1980s to more than 30% in 1990. Between 1990 and 1991, the number of reported S. enteritidis outbreaks increased more than sixfold. The 33 outbreaks reported in 1991 occurred in seven contiguous regions in northern and central Italy and were clustered in time between June and October: in the majority, products containing raw or undercooked shell eggs were implicated. Five of the egg-related outbreaks that occurred within a 30 kilometre radius over a 7 week period were investigated in detail. A phage type 1 strain containing a 38.9 MDa plasmid appeared responsible for three of the outbreaks, while in the remaining two a phage type 4 strain, also with a 38.9 MDa plasmid was isolated. Efforts are being made to enhance epidemiological surveillance and laboratory evaluation, and the use of pasteurized eggs has been recommended for high-risk populations. PMID- 8472766 TI - A large outbreak of human salmonellosis traced to a local pig farm. AB - An outbreak of Salmonella typhimurium definitive type (DT) 193 affecting 206 persons occurred in July and August 1989 in a small town in northern England. A descriptive study suggested that cold meats including pork from a butcher's shop in the town were vehicles of infection. An analytical study of a cohort attending a function in the town showed a significant association between illness and consumption of cold roast pork supplied by the butcher's shop (P = 0.00000004). S. typhimurium DT 193 with the same antibiotic resistance pattern (to ampicillin, streptomycin, sulphonamides and tetracyclines) as the outbreak strain, and possessing a single plasmid of 80 MDa was isolated from samples of meat bought from the shop and implicated in illness, and from samples of pig faeces taken from the farm supplying the shop. It was concluded that inadequate processing of infected pork meat at the shop may have contributed to this outbreak but that cross contamination also played an important part in transmission. Control measures included a temporary closure of the shop and subsequent implementation of a detailed protocol for meat processing and monitoring of all procedures at the shop. PMID- 8472767 TI - Shigellosis due to occupational contact with non-human primates. AB - A small cluster of dysenteric illness, due to Shigella flexneri, was identified among technical assistants of a primate research unit. All of the affected individuals had been in regular contact with a colony of cynomolgus macaque monkeys, one of which was known to have suffered from acute haemorrhagic colitis in the preceding few weeks. Four monkeys were found to be excreting S. flexneri bacilli of identical antigen type (1b) to that isolated from the human cases. Investigation of working practices revealed the potential for inadvertent faeco oral spread and the need to improve existing control methods. We conclude that this small outbreak of shigellosis represents a primate-associated occupational zoonosis. The risk may not be fully appreciated by handlers or their doctors. PMID- 8472768 TI - Human isolates of apramycin-resistant Escherichia coli which contain the genes for the AAC(3)IV enzyme. AB - Gentamicin-resistant Escherichia coli isolated at different periods from patients in two hospitals were tested for resistance to the aminoglycoside antibiotic apramycin. Twenty-four of 93 (26%) gentamicin-resistant isolates collected from the Royal Liverpool Hospital between 1981 and 1990 were resistant to apramycin. Thirteen isolates were highly resistant to apramycin (minimal inhibitory concentration (MIC) > or = 1024 micrograms/ml), were also resistant to gentamicin, netilmicin and tobramycin, and hybridized with a DNA probe derived from the aminoglycoside acetyltransferase (3)IV (AAC(3)IV) gene. The proportion of gentamicin-resistant isolates which had high level resistance to apramycin increased from 7% in 1981-5 to 24% in 1986-90. Twelve gentamicin-resistant E. coli from Guy's and St Thomas's Hospital isolated between 1977 and 1980 were also tested for resistance to apramycin. For five of these isolates the MICs of apramycin was 32-256 micrograms/ml. None was shown to have a conjugative plasmid carrying resistance to apramycin and only one hybridized with the DNA probe for the AAC(3)IV enzyme. PMID- 8472769 TI - A point source outbreak of campylobacter infection related to bird-pecked milk. AB - A point source outbreak of Campylobacter jejuni affected 11 children in a day nursery. Milk consumed by the children was known to have been pecked by magpies on occasions. Illness was significantly associated with consumption of milk on a single morning. Examination of milk from a bottle pecked after the outbreak yielded campylobacters. The level of contamination was approximately six cells of C. jejuni per 500 ml of milk. PMID- 8472770 TI - The seasonality of canine births and human campylobacteriosis: a hypothesis. AB - The seasonality of canine births was investigated using records from the Kennel Club and the breeding centre for the Guide Dogs for the Blind Association. In these populations a distinct seasonal pattern was found with a greater number of puppies being born in the summer months than the winter. The hypothesis that the greater number of puppies acquired as pets during the summer months may contribute to the seasonal rise in human campylobacter cases, seen at this time, is discussed. PMID- 8472771 TI - The role of management systems in the epidemiology of thermophilic campylobacters among poultry in eastern zone of Tanzania. AB - A total of 255 samples of droppings collected from a total of 22 different poultry units were examined for the presence of thermophilic campylobacters and the isolates biotyped using Skirrow's protocol. The organisms were isolated from 90 (35.3%) of all samples. Among the 22 units investigated, 13 (59%) were found to have unsatisfactory management systems, while 7 (32%) and 2 (9%) were found to have unsatisfactory and good systems respectively. Significantly large numbers of isolations, 68 of 147 (46.2%), were made from samples collected from poultry units with poor management (P < 0.005), compared with 19 out of 84 (22.6%) samples which were collected from satisfactory units and 3 out of 24 (12.5%) samples collected from units exercising particularly good management. Nineteen of 72 (26.4%) samples collected from broilers, 32 out of 132 (24.2%) samples collected from layers and 39 out of 51 (76.49%) samples collected from indigenous free range poultry were positive for campylobacters. Among the 90 strains isolated from various units, 64 (70.1%) were Campylobacter jejuni, 25 (27.7%) were C. coli, and only 1 (2.2%) was C. laridis. PMID- 8472772 TI - Adherence to HEp-2 cells and enteropathogenic potential of Aeromonas spp. AB - Aeromonas strains (total = 60) of clinical, water and food origin were tested for adherence to HEp-2 cells. Environmental strains were selected (except for A. caviae) to include primarily those expressing other virulence-associated properties. Adhesion was markedly species-dependent (A. veronii biotype sobria, 15 of 26 [58%]. A caviae, 4 of 12 [33%] and A. hydrophila, 2 of 8 [11%]). A. veronii biotype sobria were adhesive, irrespective of source (62 and 54% for clinical and environmental strains, respectively). Adherent strains of this species were enterotoxin-positive and most (13 of 15) grew at 43 degrees C. A. caviae isolated from clinical specimens contained a higher proportion (75%) of adherent strains than environmental strains (13%). Virulent subsets of A. veronii biotype sobria and A. caviae are adherent to HEp-2 cells. The HEp-2 assay is a useful model for investigating mechanisms of adherence and enteropathogenicity of virulent Aeromonas species. PMID- 8472773 TI - Antimicrobial susceptibilities and serotyping of Neisseria gonorrhoeae in southern Africa: influence of geographical source of infection. AB - One hundred and ninety-two strains of Neisseria gonorrhoeae isolated from migrant mine-workers were tested for their susceptibility to antibiotics, auxotyped and serotyped. Of the total, 93 (48%) were acquired locally and 64 (33%) from different geographical locations. Plasmid-mediated resistance to penicillin was found in 28 (14.6%) strains and was associated predominantly with the presence of 5.0 kb penicillinase encoding plasmid (18/28, 64%). Chromosomal resistance to penicillin (MIC > or = 1 mg/l) was detected in 14 (7.3%) strains. Resistance to tetracycline was chromosomally and not plasmid-mediated. Antibiotic resistance was encountered most commonly among strains acquired in Natal. The overall gonococcal population was sensitive to ceftriaxone, ciprofloxacin, spectinomycin and azithromycin. Nine auxotype/serovar (A/S) classes were encountered among penicillinase-producing N. gonorrhoeae (PPNG) compared to 24 A/S classes among non-PPNG strains. The most common A/S class was NR/IA-6 which accounted for 38% of PPNG and 15% of non-PPNG. PMID- 8472774 TI - Different seroprevalences of antibodies against Neisseria meningitidis serogroup A and Haemophilus influenzae type b in Sudanese and Swedish children. AB - Sampling of sera from 202 Sudanese and 124 Swedish children 1-14 years of age was conducted at the end of the 1980s presenting an opportunity to compare the seroprevalence of anti-Neisseria meningitidis (MC) serogroup A antibodies in an area immediately before outbreak of an epidemic (Sudan 1988) with a low endemic area (Sweden). An ELISA antibody assay was developed for detection of antibodies against capsular polysaccharide of MC serogroup A and Haemophilus influenzae type b (Hib). Serum antibody against MC serogroup A was found significantly more frequently in Sudanese than in Swedish children. This indicates that factors other than herd immunity, as measured by serum antibodies against MC serogroup A polysaccharide, are important for avoidance of an MC serogroup A epidemic. The seroprevalence of Hib antibodies was, in contrast, significantly higher in Swedish than in Sudanese children, especially for 5-9-year-old children. A possible explanation may be the different systems of day-care of children in the two countries. PMID- 8472775 TI - Bacterial load of cockroaches in relation to urban environment. AB - Sanitation is an important problem in relation to the control of pests in urban environments. This investigation analysed the potential risk related to the presence of cockroaches and their capacity for disseminating bacteria in six different types of buildings: hospital nursing area and out-patient area, swimming-pool pool-side and toilet area, low-income flats and food-handling places. Fifty-six species of bacteria were identified from 157 samples, 14 of these have previously been reported as potentially pathogenic for man and vertebrates. Similarities were found between samples collected in (a) the hospital out-patient area and food-handling establishments and (b) the hospital nursing area and flats. Pool-sides possessed a poorer bacterial flora. There was a greater bacterial specific diversity in food-handling establishments, flats and swimming-bath toilet area. Enterobacter cloacae. Klebsiella pneumoniae and Klebsiella oxytoca were dominant species in flats and the hospital nursing area. Therefore, cockroaches can play a role in disseminating bacteria, which they can carry passively on their cuticle. PMID- 8472776 TI - The prevalence of Fusobacterium necrophorum biovar A in animal faeces. AB - Only a small proportion of animals tested were found to be excreting Fusobacterium necrophorum biovar A, the causative organism of necrobacillosis, in the faeces (3 of 69 wallabies, 1 of 66 deer, 2 of 81 cattle). The two positive cattle belonged to a single group of calves on a farm with a history of necrobacillosis and the litter underfoot also readily yielded biovar A organisms. All attempts to demonstrate biovar A in litter on other farms and in soil from an area populated by wallabies and deer failed. Ruminal contents from young beef cattle proved a fertile source of F. necrophorum biovar A, 15 of 18 animals giving a positive result. It is suggested that disturbance of the gastrointestinal microflora leads to intestinal multiplication and faecal excretion of the organism, which may then give rise to necrobacillosis of the body surface. PMID- 8472777 TI - Effect of disturbance of the gastrointestinal microflora on the faecal excretion of Fusobacterium necrophorum biovar A. AB - Oral pretreatment of mice with either a mixture of kanamycin and erythromycin or metronidazole to modify the gut microflora greatly enhanced the faecal excretion of Fusobacterium necrophorum biovar A given by mouth. This lends support to the suggestion that disturbance of the gastrointestinal microflora in animals such as cattle, which often carry the organism in the rumen, may lead to intestinal multiplication and faecal excretion, thereby providing a source of infection that may lead to necrobacillosis of the body surface. PMID- 8472778 TI - Effect of respiratory syncytial virus infection on binding of Neisseria meningitidis and Haemophilus influenzae type b to a human epithelial cell line (HEp-2). AB - It has been suggested that individuals might be more readily colonized with bacteria that cause meningitis through enhanced binding of the bacteria to virus infected epithelial cells. As respiratory syncytial virus (RSV) affects infants and children in the age group also susceptible to bacterial meningitis, we tested the hypothesis that infection of HEp-2 cells by RSV might enhance binding of Neisseria meningitidis or Haemophilus influenzae type b (Hib). Attachment of fluorescein-labelled bacteria to HEp-2 cells was measured by flow cytometry, and RSV-infected cells bound significantly more meningococci (P < 0.001) and Hib (P < 0.01) than uninfected cells. Although the isolates expressed different antigenic characteristics (3 meningococci and 5 Hib), all showed a similar pattern of binding. The results are discussed with reference to the methods used for detection of bacterial binding and to interactions that might explain the increased binding to RSV-infected cells. PMID- 8472779 TI - The epidemic cycle of Chlamydia pneumoniae infection in eastern Finland, 1972 1987. AB - The epidemic cycle of Chlamydia pneumoniae infection was examined in two areas in eastern Finland over a period of 15 years, 1972-87. The C. pneumoniae IgG antibody prevalence was determined with 5-year intervals in a random sample of the population aged 25-59 years. The total number of sera studied using immunofluorescence was 2387. In 1972 the antibody prevalence was 57% and it increased to 66% in 1977. Over the next 5 years the prevalence decreased to 44% in 1982, but by 1987 it had again increased to 59%. The temporal variation in prevalence was statistically significant (P < 0.001) and similar for both genders. Throughout the observation period the overall prevalence was 7-11% higher in men than in women (P < 0.01). The antibody prevalence increased with age, being the highest among the oldest study subjects of both genders. The periods of high and low prevalence alternated in an epidemic cycle (P < 0.001) of about 10 years. PMID- 8472780 TI - Seroprevalence of HIV-1 and HIV-2 infection among children diagnosed with protein calorie malnutrition in Nigeria. AB - Excessive weight loss due to protein calorie malnutrition (PCM) is a significant problem in Nigerian children. This syndrome may be difficult to differentiate from the wasting disease caused by human immunodeficiency virus type 1 (HIV-1) infection. We studied 70 children admitted to the Baptist Medical Center in Ogbomosho, Nigeria in 1990 with PCM for prevalence of antibodies to HIV-1 and HIV 2. The cohort was from low-risk mothers and had a median age of 25 months (range, 4 months-9 years) with a weight deficit of at least 20% of the theoretical weight for age. Two sera were positive for anti-HIV-1 by both ELISA and Western blot (WB). A high prevalence of samples negative for HIV-1 antibody by ELISA were repeatedly reactive (11%, 8/70) or indeterminate (46%, 32/70) by WB. None of the sera was positive for antibody to HIV-2. There was no correlation of ELISA positivity or extent of WB banding with successful recovery from malnutrition. These results indicate a relatively low but significant prevalence of HIV-1 infection in Nigerian children with PCM. The high prevalence of indeterminate reactions in WB assays for HIV-1 suggests that other procedures may be necessary for confirmatory diagnosis of HIV-1 infection in this African population. PMID- 8472781 TI - Antenatal survey for the seroprevalence of HTLV-1 infections in the West Midlands, England. AB - The sera of 3522 women who attended an antenatal clinic in Birmingham, England were tested anonymously for antibodies against HTLV-1. Samples from 5 women (0.14%) were positive, one serum showed indeterminate reactivity. Two of the women (0.06%) were born in the West Indies (of Afro-Caribbean ethnic origin), one (0.03%) in Africa (of African ethnic origin), and three (0.09%) were white Caucasian women born in the UK. Thus, HTLV-1 infection in pregnant women in the UK, though comparatively rare, is not negligible. As transmission of HTLV-1 to the newborn via breast milk has been observed and as seropositive mothers can be advised to refrain from breastfeeding or to treat their milk, the question of routine screening for HTLV-1 infection during antenatal care is discussed. PMID- 8472782 TI - Prevalence of viral antibodies and helminths in field populations of house mice (Mus domesticus) in southeastern Australia. AB - A 13-month study of wild mice (Mus domesticus) in wheatlands in southeastern Australia contrasted changes in the seroprevalence of antibody to 13 viruses and the occurrence of helminths with changes in their population dynamics. Mice were seropositive for mouse hepatitis virus (MHV), rotavirus, minute virus of mice (MVM), mouse adenovirus (MAdV), reovirus (reo 3), and murine cytomegalovirus (MCMV). The seroprevalences of all but rotavirus varied significantly with time and increased with host density. Near the end of the study, host density declined rapidly and the seroprevalence of MVM and reo 3 increased significantly. These two viruses had low seroprevalence when host survival was high and high seroprevalence when host survival was low, indicating they may play a role in regulating mouse populations. In the case of MVM, there was evidence of a viral epizootic during the decline in mouse abundance. The prevalence of four helminths (Taenia taeniaeformis, Syphacia obvelata, and Vampirolepis spp.) differed significantly with time but showed no apparent association with host density. These findings highlight the need for further study on the effect of viruses on the population dynamics of mice. PMID- 8472783 TI - Topical norepinephrine, isoproterenol, terbutaline, forskolin and 8-bromo cyclic AMP increase lens equatorial current. AB - The equatorial current of the frog lens was studied with microelectrodes and a vibrating probe. Norepinephrine, isoproterenol and terbutaline applied topically at the surface of the cornea as a 1% solution increased the equatorial current of the lens about 80%. This increase was blocked by timolol. Topical forskolin increased the equatorial current by over 80%. This effect of forskolin was not blocked by timolol. These substances did not affect the equatorial current of the lens when the lens was suspended in a frog Ringers solution. 8-Bromo cyclic AMP increased the equatorial current when it was applied topically but not when it was added directly to the medium bathing an isolated lens. The results suggest that beta-adrenergic agonists, applied topically to the cornea, increase the equatorial current of the lens by a mechanism that is mediated by cyclic AMP. The finding that 8-bromo cyclic AMP did not act directly on the lens suggests that a currently unknown substance or process is active at the level of the lens. PMID- 8472784 TI - Effect of xylose on the synthesis of phosphorylcholine and phosphorylethanolamine in rat lenses. AB - Choline, an essential phospholipid precursor, enters the lens by a facilitated transport system and is phosphorylated to form phosphorylcholine (P-choline). Intact lenses incubated with [3H]choline accumulate both [3H]choline and P [3H]choline. The rate and extent of this accumulation have been used to study the effects of osmotic or oxidative cataractogenic stress, and also to test the ability of compounds to protect lenses from stress-related damage. The initial effect of oxidative stress on choline metabolism is decreased choline transport, but the mechanism by which osmotic stress affects the accumulation of [3H]choline is not understood. The effects of osmotic and oxidative stress on choline influx and metabolism were compared in rat lenses incubated in TC-199 medium. After osmotic stress by incubation with 30 mM xylose for up to 24 hr, lenses accumulated the same amount of radiolabel as controls during a 30 min pulse with [3H]choline. However, if the lenses were exposed to [3H]choline for 6 hr so that accumulation of radiolabel in the lenses was limited by the rate of P-choline synthesis, xylose treated lenses accumulated less choline than controls. Separation of the lenticular radiolabel into [3H]choline and P-[3H]choline confirmed that xylose decreased synthesis of P-choline, although adequate unphosphorylated [3H]choline was available in the lenses. A decrease in P [3H]ethanolamine synthesis was also seen in xylose-treated lenses incubated with [3H]ethanolamine. Ethanolamine can enter lenses by a non-saturable process which is not dependent upon a transporter. Although xylose decreased P-choline synthesis in intact lenses, neither xylose nor xylitol inhibited choline kinase in lens homogenates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472785 TI - Difference in glutathione S-transferase response to oxidative stress between porcine and bovine lens. AB - Porcine and bovine lens GSTs were compared in the stability against various oxidative stress which is a major factor of cataract formation in order to clarify the role of lens glutathione S-transferase (GST) and its relation to cataractogenesis. Class pi porcine lens GST was inactivated reversibly by biological disulfides, cystine and cystamine, and also inactivated by active oxygen species such as O2- generated through xanthine-xanthine oxidase system and H2O2. On the other hand, class mu bovine lens GST was insensitive to such applied oxidative stress. Furthermore, 1,2-naphthoquinone, which is a metabolite of naphthalene and an actual inducer of naphthalene cataract, strongly inactivated porcine lens GST though it did not affect bovine enzyme. Thus, porcine and bovine lens GSTs had different sensitivity to various oxidative stress which could induce cataract formation. The results suggest that the differential expression of GST isozymes among animals may explain the variation in the cataract formation caused by oxidative stress. PMID- 8472786 TI - 13C NMR studies of protein motional dynamics in bovine, human, rat, and chicken ocular lenses. AB - The motional dynamics of lens proteins were studied by two 13C nuclear magnetic resonance (NMR) techniques sensitive to molecular motion to define the effect of lens water content on the presence of solid-like protein domains in ocular lenses from bovine (juvenile and adult), human, rat, and chicken eyes. The solid state 13C NMR technique of proton dipolar decoupling was used to study slow (solid like) motions (correlation time, tau o > or = 10 microseconds), whereas for intermediate (mobile) protein, rotational reorientational motion (tau o range of 1-500 nsec) the 13C off-resonance rotating frame spin-lattice relaxation technique was employed. 13C NMR studies of calf lens cortical and nuclear homogenates indicated a reversible loss of lens protein motional freedom with decreasing water content. Values of 6% and 63% solid-like protein contents were obtained for native cortical and nuclear calf lens homogenates, respectively. At equivalent total protein concentrations cortical and nuclear calf lens homogenates exhibited essentially the same solid-like (motionally restricted) protein content. Lens protein rotational correlation times determined by off resonance rotating frame spin-lattice relaxation measurements were consistent with lens protein aggregation. The solid-like protein content of the bovine nuclear lens region was observed to increase with age, whereas no significant change was detected for the cortex. Across lens species an inverse correlation between the percentage of solid-like protein content and water content was observed. Very broad 13C NMR resonances, even in the presence of proton dipolar decoupling, were observed for the lens proteins present in the cataractous human lens, indicating the presence of highly aggregated protein species. The occurrence of solid-like protein domains in lens tissue has implications for the interpretation of proton nuclear magnetic resonance dispersion (NMRD) measurements of lens homogenates and for proton magnetization transfer contrast enhanced magnetic resonance imaging of lens. Solid-like protein domains may play a protective role in the maintenance of lens transparency by minimizing enhanced refractive index fluctuations created by protein packing defects resulting from post-translational modification. PMID- 8472787 TI - UV filters in human lenses: tryptophan catabolism. AB - Primate lenses are unique in that they convert tryptophan (trp) into 3 hydroxykynurenine glucoside (30HKG). This is the major short-wave absorbing pigment present in human lenses and it may play a role in protecting the eye from UV-induced photodamage. A study has been performed on aspects of this metabolic pathway in human lenses. A significant rate of synthesis could be observed in a 24-hr period using intact lenses to which radiolabelled tryptophan had been added. Label was found in kynurenine (Kyn), 3-hydroxykynurenine (30HKyn) and 30HKG, although always to the greatest extent in the latter metabolite. Considerable variation in the proportion of label incorporated into 30HKG was observed. Older lenses tended to accumulate a greater percentage into the glucoside; the data indicating a generally greater flux through the trp catabolic pathway in lenses above 60 years of age. Pulse-chase experiments on lens pairs suggested that there may be a significant loss or metabolism of 30HKG. Biosynthesis of 30HKG was found to take place in the lens epithelial cells. A linear rate of 30HKG efflux from organ cultured lenses was observed indicating that one pathway for removal of this compound involves diffusion through the lens capsule. That this pathway also occurs in vivo was confirmed by analysing samples of human vitreous humour. Based on efflux rates from cultured lenses (1.07 x 10( 3) +/- 0.293 x 10(-3) mumol hr-1, n = 5), half-life values for 30HKG in the lens ranging between 7 and 40 hr were calculated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472788 TI - Relationship between lens protein glycation and membrane structure in human cataract. AB - Glycation, which begins with the spontaneous reaction between sugar and proteins by the formation of Schiff bases, is known to especially damage long-lived proteins such as lens crystallins, and has been implicated in the ageing process and particularly in cataract formation. In this study of human senile cataract, a specific method is used to measure the formation of Amadori compounds in control postmortem and cataractous lenses, but no difference was found. However, the fluorescence of proteins at 430 nm (exc 350 nm), which has been attributed to advanced glycation, increased with normal ageing of the lens (cortex versus nucleus, and as a function of subject's age for each type of fibres) and was further enhanced in cataractous lenses. The precise molecular origin of this fluorescence remains to be elucidated. In parallel to the accumulation of non tryptophan fluorophores, a decrease in the membrane fluidity was observed with lens ageing and more acutely with cataract. Both parameters are positively correlated (P < 1%). The modification of the membrane structure with glycation could explain the strong permeability changes occurring during cataract, measured here in terms of cation concentration and inositol leakage, as shown by the negative relationship between the fluorescence signal and the sodium to potassium ratio or the inositol level. PMID- 8472790 TI - The effect of white light and UV-A on the green autofluorescence of the rabbit lens in vivo. AB - The part of the light spectrum which is responsible for an increase of lenticular green autofluorescence upon white light exposure was determined for the rabbit. The increase of autofluorescence as a function of the light energy was measured, to assess a possible threshold energy for lens alterations. Thirteen rabbits (Chinchilla Greys) were used. An area of 3 or 4.7 mm2 of the lens was exposed to light from a standard tungsten halogen lamp (250 W, lambda = 360-720 nm). Wavelength selection was performed with the use of light filters. The light dose was adjusted by varying the exposure time between 15 min and 180 min. The green lenticular autofluorescence (lambda exc = 420-490 nm, lambda fluor = 530-600 nm) was measured with a fluorophotometer. A significant increase of lenticular autofluorescence after exposure was observed only if the exposure light contained high wavelength UV-A (lambda = 360-400 nm; 0.8% of the total white light energy); additional white light (without UV-A; up to 13 kJ cm-2) did not have any effect on autofluorescence. The autofluorescence returned to pre-exposure values within 4 days. No lesions could be seen on slitlamp examination. The autofluorescence after exposure to UV-A increased linearly with the exposure energy from 13 J cm-2 (14 mW cm-2 for 15 min) up to 155 J cm-2. The increase was 2.0% of the pre exposure value per J cm-2 and the correlation coefficient 0.94, P < 0.001. A threshold energy was not found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472789 TI - Alterations in viscosity and filterability of whole blood and blood cell subpopulations in diabetic cats. AB - Capillary closure and venous dilatation occur early in diabetic retinopathy, and altered blood rheology may play a role. For example previous studies have shown leukocytes are less deformable, are more activated, and occlude retinal capillaries more often in diabetic subjects. The purpose of this study was to determine if rheologic changes developed in diabetic cats, a model in which we have documented retinal capillary basement membrane thickening, microaneurysms, and intraretinal hemorrhage characteristics of early diabetic retinopathy. Viscosity of blood, plasma and purified erythrocyte suspensions was measured by rotational viscometry and plasma fibrinogen content was determined by heat precipitation. Filterability of blood and purified erythrocyte, mononuclear leukocyte, and granulocyte suspensions was determined at constant flow, measuring the increase in pressure over 2 min relative to the pressure generated by buffer alone. Viscosity of whole blood and plasma, but not erythrocytes, was significantly elevated (P < 0.005) in the diabetic cats over normals at all shear rates studied (450, 225 and 90 sec-1). Furthermore, fibrinogen levels were significantly elevated in diabetic cats compared to normals (P < 0.004), and were positively correlated with the viscosity of whole blood and plasma. The filterability of mononuclear leukocytes and whole blood in diabetic cats was decreased 56% and 74% when compared to normals, P < 0.0006 and P < 0.025, respectively. In contrast, the filterability of granulocytes and erythrocytes was not significantly different between the two groups. These results suggest that the rheologic alterations in diabetes are numerous, and involve both cellular and plasma protein changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472791 TI - A simple three-compartment model of anterior segment kinetics. AB - Diffusion of fluorescein between the plasma and anterior chamber has been considered a one-step process with transfer coefficient kd. However, after systemic administration, fluorescein enters the anterior chamber by a different kinetic than this simple model predicts. In this study we added to the model another compartment, the 'iris', between the plasma and anterior chamber. When fluorescein diffuses into the anterior chamber, it must cross two barriers, one between plasma and iris with coefficient ki.ip, and one between iris and anterior chamber with coefficient ki.ia. Fluorescein was measured in the anterior chamber after intravenous injection and was compared to fluorescein concentration calculated by using both kinetic models, the three-compartment model (iris, anterior chamber, and cornea) and the two-compartment model (anterior chamber and cornea). Transfer coefficients were determined by the method of least squares in 12 pigmented rabbits and two groups of six human subjects measured in two previous fluorophotometry studies. In all subjects except one, the three compartment model matched the data better than the two-compartment model. In a second experiment, diffusion of fluorescein out of the anterior chamber was studied in 15 pigmented rabbits. Diffusional loss was determined from the relative clearances of rhodamine-labeled dextran, a large molecule that left only by bulk outflow, and fluorescein that was cleared by diffusion and outflow. The upper 95% confidence limit of diffusional clearance was less than 11% of total clearance in anesthetized rabbits. PMID- 8472792 TI - Identification of a gamma S-crystallin fragment in human lenses. PMID- 8472793 TI - Does dopamine act at dopamine receptors in the ciliary epithelia? PMID- 8472794 TI - On the identity of the cone types of the rat retina. PMID- 8472795 TI - A computer program for application in epidemiological analysis. AB - The importance of computer science as a working tool for the health sector is an unquestionable fact in any modern society. EPIDEMO, developed by the authors, can be defined as a set of programs whose main characteristic is its ability to process a given series of data in a totally integrated way, with an epidemiological and statistical approach. EPIDEMO is a program with a good relational database, which allows preliminary statistical analyses of data that can easily be expanded with more specific statistical options, and is compatible with other programs available on the market. It is a useful, accurate and versatile tool that meets the needs of health professionals in the field of epidemiological research. PMID- 8472796 TI - Planning of a screening programme for cervical cancer in Liguria and evaluation of the attitude of the female population towards cancer detection. AB - In 1990 an investigation aimed at evaluating the possibility of organizing a regional screening programme for the early detection of cervical cancer was carried out in Liguria. Information on resources available for early detection of cervical cancer was obtained from 12 of 20 Public Health Units; a screening programme was feasible in 8 of them. The number of Pap tests examined was evaluated for 6 of 20 cytology laboratories. Only one laboratory examined more than 20,000 Pap tests in 1989 and, according to the international guidelines, can be a referring centre for screening. However, no information was available concerning inter- and intralaboratory quality control programmes. In the same period a population-based survey was carried out using a self-administered questionnaire in order to evaluate the attitudes of women towards cervical cancer prevention. A total of 1,454 of 4,197 women (35%) participated in the study. Younger, well educated women employed in non non-manual work were more likely to participate in the study. About 65% of the respondents had satisfactory practices with regards to the Pap test, suggesting a strong self-selection that probably resulted in a sample of women more health-conscious than the general population. In conclusion, our results suggest that major interventions should be carried out in the Public Health Units to direct resources to the needs of the population. In addition, new educational methods should be adopted to reach selected population groups to encourage them to have a Pap test performed on a regular basis. PMID- 8472797 TI - Lifetime menstrual activity--indicator of breast cancer risk. AB - A case-control study of 67 cases of breast cancer and 157 controls was conducted to investigate the role of different behavioral, reproductive, and hormonal factors and to develop a unifying indicator of breast cancer risk. The results confirm previous reports of the influence of smoking on the risk of breast cancer. Age at menarche was found to be a risk factor among the premenopausal women. Late age at menopause was suggestive of an increase in risk. Long use of oral contraceptive or estrogen supplementation were risk-enhancing both pre- and postmenopausally. Lifetime duration of menstrual activity (LMA) combines age at menarche and menopause, parity, and lactation into a biologically plausible model. Our findings concerning LMA support its role as a determinant of breast cancer. PMID- 8472798 TI - Familial risk of colo-rectal cancer in a low incidence area in southern Italy. AB - The risk of colo-rectal cancer (CRC) in subjects with a positive family history (FH+) for malignancy has been assessed by means of a case-control study carried out between 1987-89 in an area of about 215,000 inhabitants in Southern Italy. One hundred and nineteen CRC cases were compared with 119 sex- and age-frequency matched population controls. Detailed pedigrees were collected at the family homes of both cases and controls. The odds ratio (OR) of CRC, adjusted by means of logistic regression for age, sex and number of first-degree relatives, increased with the number of any kinds of cancers in first-degree relatives with a significant linear trend (p = 0.042), while there was no risk with a FH+ for digestive cancer excluding CRC or for other cancers excluding large bowel and digestive organs. The OR (and 95% confidence interval) for CRC was 5.9 (1.64 21.23) for at least one first-degree relative with CRC. After a mutual adjustment between CRC and the other cancers in the families of cases and controls, the risk of CRC with a FH+ for other cancers did not change, revealing a strong association (p = 0.002) for CRC alone. From the analysis of the family history of cancer in the case group, the relative frequency of families that satisfied the criteria for so-called hereditary non-polyposic colo-rectal cancer (HNPCC) was 2.6%. The increased relative risk of CRC observed only in families with FH+ for CRC is a supportive finding for organizing and planning prevention and genetic counselling for these families, whose members should be referred for further assessment. PMID- 8472799 TI - Testing a new health indicator: using avoidable causes of death and life expectancy for Spain between 1975-1986. AB - The concept of avoidable cause of death serves as the basis for measuring the quality and diversity of a health care system. In this study the authors propose a new way to use this kind of mortality by combining with the concept of life expectancy to obtain what they call "life expectancy free of avoidable mortality" (LEFAM). This indicator was 76.9 in 1986 in Spain while life expectancy was 75.83. If these deaths were avoidable there would be a gain of 1.09 years per person born. There is an important difference between the would-be male gain of 1.76 years and the would-be female gain of 0.6. In the ecological study, LEFAM would better explain the year to year changes of the resources in the health sector, measured in terms of the human resources (R = 0.96), the hospital beds per thousand persons (R = -0.86), and would also increase the relation with other health indicators such as infant mortality rate (R = 0.98) and mortality rate (R = 0.59) as compared with life expectancy alone. PMID- 8472800 TI - Alcohol drinking among adolescents from town and mountainous areas in north Italy. AB - Alcohol consumption was investigated among 9th and 13th grade high school students in the town of Brescia (an urban area) and in the Local Health Unit of Breno, a mountainous area in the province of Brescia. A total of 1364 students from Brescia and 1373 from Breno completed an anonymous questionnaire during school time. In both groups alcohol consumption was greater among 13th graders (modal age: 18 years) and males than 9th graders (modal age: 14 years) and females. Beer was the favourite alcoholic beverage, but wine was the most widely consumed daily beverage: among males, about 8% in grade 9 and 15% in grade 13 drank at least one glass of wine every day. The majority of both 9th and 13th graders had more than one type of alcoholic beverage a week, although many females drank beer only. Total alcohol consumption was higher among the mountainous area students than urban students, especially 9th graders, and greater differences were observed in the consumption of beer with respect to wine. The proportion of male students from Brescia and Breno who consumed more than 6 alcohol units a week were, respectively, 17% and 25% in grade 9 and 36% and 42% in grade 13. A higher prevalence of drunkenness was found among the students from the mountainous area with respect to the urban students, especially males. Among 13th grade males, 42% of students from Brescia and 60% from Breno claimed one or more episodes of drunkenness during the year prior to the interview. PMID- 8472801 TI - Census in a rural area of Ethiopia: methodology and results. AB - A census and an ecologic survey were performed in 39 villages of a rural district of Arsi Region, Ethiopia, in difficult field circumstances. Information on age, ethnic group, education and family relationship, as well as data on health facilities and availability of basic services were collected. Supervised students, working in teams, were used as interviewers. Communities were involved through plenary meetings and community health agents participated in the data collection process. A total of 64,714 people in 12,152 households were registered. The repeatability of age assessment was investigated by comparing the results from two villages with data obtained in a pilot study carried out 6 months earlier. The technical error was only 0.80 and 1.67 in the 0-5 and 6-15 age-groups, respectively. Three percent of the total population was under one year, less than previously estimated. This may, in part, be due to the family planning programme in the region. Eighteen percent of the households were headed by females. School attendance was less common among females and in the Oromo ethnic group. The availability of basic services, including safe water and basic sanitation supplies, was very poor in the area. PMID- 8472802 TI - Antigens of Rickettsia conorii recognized by seropositive healthy people from Salamanca (central-west Spain). AB - The antigenic reactivity in Western immunoblotting assay of individual Rickettsia conorii components with sera of healthy people living in Salamanca Province, an endemic zone of Mediterranean spotted fever, is evaluated. Polypeptides of molecular weights 100 kDa (92.7%), 135 kDa (75.6%), 160 kDa (70.7%) and 115 kDa (48.8%) were recognized by a higher proportion of sera with indirect immunofluorescent antibody test titers > or = 1:80. Reaction with apparent rickettsial lipopolysaccharide was found in 15 (36.6%) of these samples. The involvement of different rickettsial strains, atypical routes of inoculation, varying content of the inoculum, and host factors may be determinants of the clinical expression of the spotted fever group rickettsial infection in people who produce antibodies reactive with Rickettsia conorii antigens. PMID- 8472803 TI - Antimicrobial resistance among clinical isolates of Haemophilus influenzae in northern Italy. Collaborative Study on Pediatric Infectious Diseases. AB - Only scanty data are available on the susceptibility of Haemophilus influenzae in Italy. The in vitro activity of ampicillin, ampicillin-sulbactam, cefaclor, cefuroxime, cefotaxime, chloramphenicol, erythromycin and trimethoprim sulfamethoxazole against 327 strains of Haemophilus influenzae (55 encapsulated, 272 non-typeable) isolated from adults and children in northern Italy, between January 1984 and December 1989, was compared. Patients were affected by meningitis or other invasive infections, conjunctivitis, otitis, sinusitis, pneumonia or bronchitis. Minimal inhibiting concentrations were determined by a microdilution technique in Mueller Hinton broth supplemented with 10 microliters/ml NAD and 2-5% lysed horse blood. A concentration of 1 x 10(5) to 5 x 10(5) CFU/ml was used as the inoculum. The antibiotics were tested at concentrations ranging from 0.03 to 64 microliters/ml with the exception of trimethoprim-sulfamethoxazole, for which the range of concentrations examined were 0.01/0.25 to 32/512 microliters/ml. All the strains tested were susceptible to ampicillin-sulbactam, cefuroxime and cefotaxime, and more than 95% were susceptible to ampicillin, cefaclor and chloramphenicol. Only 4% were susceptible to erythromycin but most minimal inhibiting concentrations fell into the intermediate category. Strains isolated from adults were more susceptible to trimethoprim-sulfamethoxazole than strains isolated from children (85% vs 66%; p = 0.011). PMID- 8472804 TI - Treatment and serological studies of an Italian case of penicilliosis marneffei contracted in Thailand by a drug addict infected with the human immunodeficiency virus. AB - A case of disseminated penicilliosis marneffei, the first to be diagnosed in Italy, is described in a male HIV-positive drug addict. The patient had visited Thailand several times in the two years prior to his hospitalization. The presenting signs were fever, productive cough, facial skin papules and pustules, nodules on both thumbs and oropharyngeal candidiasis. Penicillium marneffei was isolated from a series of blood specimens with the lysis centrifugation procedure. Septate, yeast-like cells were observed in histological sections of the nodules and sputum smears. The patient was treated for 6 weeks with amphotericin B (total dosage 1,400 mg) and flucytosine (150 mg/kg/die) for the first 3 weeks. Prompt clinical improvement and sterilization of all biological specimens were attained. Itraconazole was administered as maintenance therapy (400 mg/die for the first month and 200 mg afterward). During the follow-up period, no relapse was observed. The patient, however, did succumb to a variety of non-mycotic infections and died nine months after start of therapy. At autopsy, P. marneffei was not detected in his tissues. Serological studies were performed with a micro-immunodiffusion procedure using a mycelial culture filtrate antigen of P. marneffei. Sera taken early in the course of the disease gave positive antibody reactions. Whereas sera taken 3-5 months following therapy were negative. All known cases of penicilliosis marneffei in bamboo rats and in humans among the inhabitants and visitors to the endemic areas of P. marneffei in South East Asia and Indonesia are summarized. PMID- 8472805 TI - Advances in investigations of Lyme borreliosis in the territory of the former USSR. AB - Whereas late manifestations of Lyme borreliosis were described in Russia more than 100 years ago, early manifestations were described as different disease entities such as tick-borne erythema, etc. In 1985 Lyme borreliosis was first verified serologically and the agent was first identified in 1986. By the beginning of 1992 Lyme borreliosis was serologically confirmed in patients from the Baltics to the Far East. Their geographical patterns in Russia are closely related to areas of the hard ticks Ixodes persulcatus and Ixodes ricinus which are also the main vectors of tick-borne encephalitis virus. As in the case of this infection, in the west of Russia there are "ricinus" natural foci of Lyme borreliosis, and to the east there are similar "persulcatus" foci; through large territories in the East Europe there are common foci for both species. Many Borrelia burgdorferi strains of tick origin have been isolated from various regions of Russia and neighbouring republics. Adult tick infection rates vary from several per cent to 30% in I. ricinus and up to 50-60% in I. persulcatus. Double infections of Lyme borreliosis spirochetes and tick-borne encephalitis virus have been recorded for ticks as well as for humans. Lyme borreliosis morbidity and its importance for the Russia territory are discussed. PMID- 8472806 TI - Evaluation of a passive microcapsule agglutination test for the screening of human leptospirosis. AB - Microcapsules, absorbed with two mixed antigens--each composed of 3 sonicated leptospira serovars--were developed in the past as a microcapsule agglutination test (MCA-LS) for the screening of clinical leptospirosis. For this study, fifty serum samples, taken at an earlier and at a later stage of illness from 25 Italian in-patients with clinical symptoms of leptospirosis, were tested with both the MCA-LS one-dilution test and the microscopic agglutination (MA) test, the confirmatory test for leptospirosis, with 18 leptospira strains circulating in Italy. Compared with MA, MCA-LS showed a sensitivity of 91.7%, and a specificity of 92.3%, including leptospirosis not sustained by the diagnostic strains used in the MCA-LS kit. PMID- 8472807 TI - Diagnosis of Mycoplasma pneumoniae infection by specific IgM antibodies using a new capture-enzyme-immunoassay. AB - A total of 1226 sera from 1055 patients with respiratory tract infections were tested. IgM antibodies were detected by an antibody-capture enzyme-immunoassay (Mp TEST, Diatech Diagnostica Ltd, Israel). Acute infection with IgM antibodies to Mycoplasma pneumoniae was detected in 211 patients. Presence of IgM was closely associated to some or all pneumonia-related symptoms. Eighty-one of IgM positive patients treated with tetracycline or erythromycin responded positively. Of the 211 patients, 63 (30%) had low levels and 23 (11%) had moderate levels of IgM antibodies already in the first serum sample. In these 86 patients (41%) the complement fixation (CF) test was negative or very low positive. Thus in these cases, the CF test would have missed the early diagnosis in the first serum samples. PMID- 8472808 TI - Misincorporation of uracil into the DNA of folate- and B12-deficient HL60 cells. AB - HL60 cells were cultured for 10 days under various experimental conditions. They were then incubated with 1 mumol/l [5-3H] uridine for 2 hours and their DNA extracted. The DNA was hydrolysed to deoxyribonucleosides with phosphodiesterase and alkaline phosphatase and the hydrolysate subjected to Aminex A6 chromatography. The elution profiles showed that, when compared with control cells, DNA from cells grown in medium deficient in folate, B12 or both folate and B12 contained increased amounts of deoxyuridine (dU) and increased radioactivity in the dU peak. The data demonstrate that misincorporation of uracil into DNA occurs in a myeloid cell line cultured in growth medium deficient in folate, B12 or both folate and B12. PMID- 8472809 TI - Interleukin-4 induces proliferation of adult T-cell leukemia cells. AB - To evaluate the effect of IL-4 on the growth of leukemic cells from adult T-cell leukemia (ATL) patients (ATL cells) and determine whether the IL-4 autocrine mechanism is involved in the growth of ATL cells, we studied the proliferative response of ATL cells, from 11 patients, cultured in the presence or absence of IL-4 in vitro. Leukemic cells from 10 of the 11 patients examined proliferated in response to both IL-2 and IL-4 in a dose-dependent manner. The proliferative response to IL-4 was higher than that obtained with IL-2 in 8 patients. The expression of the IL-2 receptor (IL-2R) alpha alpha-chain in leukemic cells from some patients was also enhanced by IL-4. The IL-4 receptor was demonstrated by flow cytometry on the surface of ATL cells. Neither IL-4-induced proliferation of ATL cells nor IL-4-induced IL-2R expression on ATL cells was inhibited by anti Tac or anti-IL-2 antibody and, therefore, these effects of IL-4 are considered independent of endogenous IL-2 activity. However, IL-2 and IL-4 were undetectable in the culture supernatants of ATL cells from any patient by enzyme-linked immunosorbent assay. Interferon-gamma (IFN-gamma) partially inhibited IL-2 or IL 4-induced proliferation of ATL cells. These results suggest that leukemic cells from ATL patients proliferate by an IL-2 or IL-4 paracrine mechanism in lymphoid tissue in vivo and that IFN-gamma inhibits IL-2- or IL-4-induced proliferation of ATL cells. PMID- 8472810 TI - Plasma and cellular pharmacokinetics of m-AMSA related to in vitro toxicity towards normal and leukemic clonogenic bone marrow cells (CFU-GM, CFU-L). AB - Plasma and cellular pharmacokinetics of m-AMSA were investigated in 5 patients with acute leukemia, using HPLC. The pharmacokinetic data served as a guideline for in vitro toxicity tests on clonogenic bone marrow cells. m-AMSA was administered as a 3-hour intravenous infusion of 100 mg/m2. Median plasma and nucleated blood cell peak concentrations were 1.25 and 6.36 micrograms/ml followed by biphasic elimination with a median T1/2 alpha alpha of 1.6 h and 0.3 h and a median T1/2 beta of 5.0 h and 5.0 h respectively. Median plasma and cellular area under the curve (AUC) for a 24-h period amounted 6.2 micrograms.h/ml and 49.8 micrograms.h/ml respectively. In vitro cellular uptake was maximal at least within 30 minutes. No differential toxicity for CFU-GM and CFU-L was observed in relation to exposure time. Median IC50 for CFU-GM and CFU-L was 2.2, 1.8 and 1.6 micrograms/ml after incubation periods of resp. 0.08, 4 and 24 h. The corresponding m-AMSA concentration x time products to achieve 50% inhibition (IAUC50) were 0.18, 7.2 and 38.4 micrograms.h/ml, respectively. 48-h prestimulation of the clonogenic bone marrow cells with Human Placenta Conditioned Medium increased sensitivity (median 1.7 x) after 4 h incubation with mAMSA. Short exposure provides maximal, concentration-related, cellular uptake, resulting in effective inhibition of growth of clonogenic bone marrow cells. PMID- 8472811 TI - A retrospective analysis of bleeding complications in 438 patients with acute leukaemia during the years 1972-1991. AB - The incidence and mortality of bleeding complications have been investigated in 438 patients with acute leukaemia consolidated either by chemotherapy (n = 241) or by bone marrow transplantation (n = 197). Bleeding signs on admission were found in 38% of the chemotherapy-treated group. Haemorrhagic deaths during the 1st month were seen in 10%. The majority of the major bleedings were localized intracranial, but gastrointestinal haemorrhages were also common. The platelet count was significantly lower (40 x 10(9)/l versus 69 x 10(9)/l, p < 0.001) and the leukocyte count significantly higher (31.2 x 10(9)/l versus 11.6 x 10(9)/l, p < 0.001) in the group with bleeding complications than in those without. The haemorrhagic mortality in patients consolidated with chemotherapy compared with transplant patients was similar, 23% and 19%. The majority of the lethal haemorrhages in the latter group were observed in patients undergoing allogenic bone marrow transplantation after engraftment. Septicaemia, graft-versus-host and venous occlusive disease were contributing factors. PMID- 8472812 TI - Improved survival and marrow engraftment of mice transplanted with bone marrow of GM-CSF-treated donors. AB - Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administered to bone marrow (BM) transplant recipients is associated with earlier recovery. We have investigated the possibility of stimulating normal donor mice in vivo with GM-CSF. Donor balb/c mice were injected i.p. with GM-CSF (5000 u) or saline. Seventy-two hours later 5 x 10(5)BM cells from either GM-CSF-treated or control donors were infused into lethally irradiated (850 R) recipients. In the recipients of BM from GM-CSF-treated donors, significantly higher CFU-S and significantly higher survival rate (57% [n = 65]; vs. 30% [n = 63]; p < 0.05) were noted. Donor mice of the GM-CSF group did not differ in bone-marrow cellularity and composition from their controls. However, recipients of BM from GM-CSF-treated mice had higher blood counts of haemoglobin, leukocytes and platelets compared to controls. These data demonstrate that pretreatment of BM donors with GM-CSF may be of benefit in improving survival and marrow engraftment in mice. PMID- 8472813 TI - Bezafibrate-induced neutropenia. PMID- 8472814 TI - Hodgkin's disease and Sjogren's syndrome. PMID- 8472815 TI - Autoimmune hypothyroidism and granulocyte-macrophage colony-stimulating factor. PMID- 8472816 TI - Influence of human serum on human bone-marrow-derived stromal cell layers. PMID- 8472817 TI - Focus on mesothelioma and the mesothelial cell. PMID- 8472818 TI - Chemoprevention of cancer. PMID- 8472819 TI - Analysis of longitudinal data: choosing and interpreting regression models. PMID- 8472820 TI - Muscarinic receptor subtypes in airways. PMID- 8472821 TI - How the lung deals with oxidants. PMID- 8472822 TI - Reliability of a monitoring system for respiratory emergency room admissions. AB - A respiratory emergency room admissions monitoring system (RERAMS) was set up in Barcelona between 1985-1989, in order to investigate asthma epidemics in the city. Information on emergency room admissions for asthma and chronic obstructive pulmonary disease (COPD) was recorded daily from the four main hospitals of the city. The present study aims at assessing the reliability and coverage of this monitoring system. Identification of asthma and COPD emergencies was repeated by a reference observer, following the same protocol to extract data as that used by the register. To assess the coverage of the monitoring system, information was collected over 28 randomly selected days, from the emergency room clinical records for the seven additional hospitals in the city with five or more daily emergencies. Identification of asthma emergencies was highly reliable (kappa value, kappa = 0.81) as was the discrimination between asthma and COPD diagnoses (kappa = 0.91). Reliability for emergencies classified as COPD was lower, but still good (kappa = 0.65). The monitoring system covered 76 and 78% of all Barcelona asthma and COPD emergency room admissions, respectively. Emergency room admissions from our monitoring system did not differ in terms of social and demographic characteristics from emergencies recorded at the other hospitals. We conclude that the monitoring system for the Barcelona respiratory emergency room admissions was highly reliable, which suggests that, when adequately collected, information from clinical records of respiratory emergencies could be used for environmental epidemiological purposes. PMID- 8472824 TI - Vital prognosis in intrathoracic sarcoidosis with special reference to pulmonary function and radiological stage. AB - A follow-up of 254 patients with intrathoracic sarcoidosis has been carried out after a median of 27 yrs from the diagnostic admission. All patients could be traced. At the end of follow-up there was no excess mortality (80 deaths observed versus 65.5 expected). However, during the first 20 yrs of follow-up a slight excess mortality was seen. Thirty three out of the 80 deaths were related to sarcoidosis. No excess number of deaths from lung cancer or lymphoma was observed. Erythema nodosum was of no prognostic significance concerning survival. X-ray stage was related to survival with a significant excess mortality for stage 3. Early clearing of X-ray changes gave a favourable vital prognosis. Survival was related to lung function, and for forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) index and total lung capacity (TLC) this relationship reached levels of statistical significance. In multivariate Cox regression models, with age and sex entered as covariates, the same parameters were found to be significant predictors of mortality. Patients with FEV1 < or = 50% predicted had an increased mortality risk of 4.2 (95% confidence interval 1.8 9.6) when compared to patients with FEV1 > 80% predicted. Likewise, patients with TLC < or = 80% predicted had a mortality risk of 2.6 (1.5-4.5) when compared to patients with TLC > 80% predicted. In conclusion, a modest excess mortality was observed during the first 20 yrs of follow-up. Furthermore, both X-ray staging and lung function at the time of diagnosis influenced long-term mortality in patients with intrathoracic sarcoidosis. PMID- 8472823 TI - Longitudinal methods for describing the relationship between pulmonary function, respiratory symptoms and smoking in elderly subjects: the Tucson Study. AB - In this study recently developed longitudinal techniques are used to examine the relationship between respiratory symptoms, smoking and pulmonary function measures in elderly subjects. The subjects were participants in the Tucson Epidemiological Study of Airways Obstructive Disease, aged > or = 55 yrs at the first survey 1972-1973, who had received pulmonary function testing and completed questionnaires in at least one of the six selected surveys. There were 633 males and 891 females, with up to 14 yrs follow-up included in the analysis. Based on their questionnaire responses, subjects were classified according to their respiratory symptoms and smoking habits at each survey. The pulmonary function testing included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and their ratio (FEV1/FVC). The pulmonary function data were analysed gender specific, with and without stratifying on vital status. The results indicate that respiratory symptoms are generally associated with lower levels of lung function, and that the impairment associated with chronic cough was observed predominantly in male subjects. The negative association of smoking was apparent in most measures, but was largest and most progressive in the FEV1/FVC ratios. Ex-smokers, in all cases, had better lung function values than current smokers, but their mean curves were always significantly below the values of nonsmokers. PMID- 8472825 TI - Is lung retransplantation indicated? Report on four patients. AB - As more lung transplantations are performed, many patients will suffer graft failure and will be considered for retransplantation. This article reviews the case management reports of four patients who received lung or heart/lung retransplantation, with overall disappointing results. The pros and cons of lung retransplantation are discussed. PMID- 8472826 TI - Effects of intrinsic PEEP on pulmonary gas exchange in mechanically-ventilated patients. AB - The aim of the study was to assess the impact of the intrinsic positive end expiratory pressure (PEEPi) on pulmonary gas exchange in mechanically-ventilated patients, by comparing the effects of similar levels (0.8-0.9 kPa) of positive end-expiratory pressure (PEEP) and PEEPi. Ten patients with acute respiratory failure, without chronic airway disease, were studied with three ventilatory modes: 1) intermittent positive pressure ventilation with zero end-expiratory pressure (ZEEP mode); 2) continuous positive pressure ventilation with PEEP set by the ventilator (PEEP mode); and 3) intrinsic PEEP elicited by adequate shortening of the expiratory time (PEEPi mode). Cardiorespiratory variables (e.g. respiratory compliance and resistance, arterial and mixed venous blood gases, cardiac output, pulmonary capillary pressure, oxygen delivery) were measured during each ventilatory mode. Compared to ZEEP, both PEEP and PEEPi decreased cardiac output while increasing arterial oxygen tension (PaO2). However, the improvement of PaO2 was more consistent (8 out of 10 patients), and larger (+2.1 kPa, on average, p < 0.05) with PEEP than with PEEPi (5 out of 10 patients, and +1.4 kPa, on average, NS). Since the effects of PEEP and PEEPi on ventilation, lung volume, compliance, cardiac output (QT), mixed venous oxygen tension (PvO2) and oxygen consumption (VO2) were similar, we attributed the less favourable impact of PEEPi on PaO2 to a less homogeneous distribution of PEEPi between lung units with different time constant, and hence to a more uneven distribution of the inspired gas. PMID- 8472827 TI - Comparison of nasal pressure support ventilation with nasal intermittent positive pressure ventilation in patients with nocturnal hypoventilation. AB - Nasal intermittent positive pressure ventilation (NIPPV) provides effective ventilatory support in patients with nocturnal hypoventilation. Nasal pressure support ventilation (NPSV), which only provides ventilation in response to patient triggering, may also be effective, simpler, and cheaper, but has not been evaluated. NIPPV and NPSV were compared in 12 patients with nocturnal hypoventilation, requiring domiciliary ventilatory support. The patients were studied on three consecutive nights, in random order: a control night without ventilation and a night on each mode of ventilatory support using the bilevel positive airway pressure (BiPAP) ventilator. Both NIPPV and NPSV significantly increased mean arterial oxygen saturation (SaO2) compared to the control night (NIPPV mean increase 4.1%; 95% confidence interval (CI) 2.2 to 6.1, NPSV 4.4%; CI 2.1 to 6.6) with no significant difference between the two modes. The percentage of the study night spent below 90% SaO2 was significantly reduced by both ventilator modes compared to the control night (median reduction on NIPPV 37%; CI -54 to -10, reduction on NPSV 31%; CI -53 to -9, with no significant difference between NPSV and NIPPV. NPSV was as effective as NIPPV in patients with nocturnal hypoventilation, which suggests that these patients are able to trigger the ventilator adequately. The lower cost of NPSV will make it accessible to more patients with chronic lung disease. PMID- 8472828 TI - The muscarinic M1-receptor-selective antagonist, telenzepine, had no bronchodilatory effects in COPD patients. AB - In a double-blind, placebo-controlled, randomized, cross-over trial, we studied the effects of the muscarinic M1-receptor-selective antagonist (+/-)-telenzepine (3 mg orally at 6 p.m. for 5 days) in 21 patients with chronic obstructive pulmonary disease (COPD). At enrollment all patients showed at least a 50% decrease in airway resistance (Raw) after inhalation of 400 micrograms fenoterol or 200 micrograms oxitropium bromide. Telenzepine did not have a significant effect on forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Also, no significant changes could be detected in daily spirometric profiles or Raw. The results indicate that short-term treatment with the M1 selective antagonist, telenzepine, does not improve airway function in COPD patients, at least after administration by the oral route. PMID- 8472829 TI - Minor acute effect of an inhaled corticosteroid (budesonide) on bronchial hyperresponsiveness to methacholine in children with asthma. AB - Several studies have shown that long-term administration of inhaled corticosteroid reduces airway hyperresponsiveness. This study was performed in order to exclude an acute effect of inhaled corticosteroid. In a double-blind, randomized, cross-over study, children with asthma, who had never used inhaled or oral corticosteroid, received a single dose of 0.8 mg budesonide or placebo on two separate days, with an interval of at least 48 h. On each test day, baseline forced expiratory volume in one second (FEV1) and methacholine responsiveness (expressed as provocative dose producing a 20% fall in FEV1 (PD20) to methacholine, in doubling dose) were measured. Both measurements were repeated 2 and 5 h after administration of the drug. Twenty children were included in the study. FEV1 showed a mean increase of 1% at 5 h on the budesonide day, and a decrease of 2% on the placebo day (p = 0.01). PD20 increased by 0.1 doubling dose on the budesonide day, and decreased by 0.4 doubling dose on the placebo day. These changes are within the measurement variation (p = 0.06). We conclude that a single dose of 0.8 mg budesonide has a minor effect on methacholine responsiveness 5 h after administration in children with asthma. It is unlikely that such an effect interferes with the interpretation of data collected in long term studies. PMID- 8472830 TI - Bronchodilator effect of nebulized sodium cromoglycate in children born prematurely. AB - We wished to determine whether nebulized sodium cromoglycate (SCG) has bronchodilator effects in very young children. In 18 children born prematurely and studied at a median of 15 months of age, thoracic gas volume (TGV) and airways resistance (Raw), were measured and hence specific airways conductance (sGaw) was calculated before (baseline) and after nebulized saline, and then after sodium cromoglycate. sGaw improved significantly in 10 infants after SCG, compared to only in two following saline. These preliminary results suggest that nebulized SCG may have an acute bronchodilator effect in some children born prematurely. PMID- 8472831 TI - Acute exposure to swine dust causes bronchial hyperresponsiveness in healthy subjects. AB - Six urban subjects, with little or no previous experience of farm-work, were exposed to dust while weighing swine for 2-5 h. Three subjects experienced toxic symptoms 4-5 h after the beginning of exposure. Bronchial responsiveness increased in all subjects within 6 h (more than three doubling steps difference in a methacholine test). One week later, airway responsiveness had partly normalized. The mean (interquartile range) cumulative dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV1) was 3.1 (1.0-6.6) mg, before exposure, fell to 0.13 (0.01-0.76) mg 6 h after exposure (p < 0.02), and was 0.99 (0.42-1.5) mg one week later (n = 5, p < 0.05), Mean (SD) FEV1 decreased 5 (2)%. The concentration of total dust varied between 9 and 14 mg.m-3 and of endotoxin between 0.1 and 0.5 mu g.m-3. Thus inhalation of swine farm dust, caused a marked increase in bronchial responsiveness in non-sensitized subjects. PMID- 8472832 TI - Bronchoalveolar lavage in allergic granulomatosis and angiitis. AB - Pulmonary involvement occurs in approximatively half of patients with allergic granulomatosis and angiitis (AGA). We studied bronchoalveolar cells from six patients with histologically proven AGA and compared our results with those obtained from four patients with chronic eosinophilic pneumonia (CEP), nine nonsmoking patients with bronchial asthma and blood eosinophilia, and 10 healthy nonsmokers. Pulmonary infiltrates were present in 5 out of 6 AGA patients. None of these patients was receiving corticosteroids at the time of entry to the study. Pulmonary function tests were normal in two cases, and demonstrated on obstructive ventilatory disorder with hypoxaemia in four cases. Total cell yield did not differ between AGA patients (22.4 +/- 4.9 x 10(4) cells.ml-1), asthmatics (9.6 +/- 1.7 x 10(4) cells.ml-1) and controls (11.3 +/- 1.5 x 10(4) cells.ml-1), whereas it was dramatically increased in patients with CEP (186.4 +/- 26.3 x 10(4) cells.ml-1). All six AGA patients demonstrated an increased percentage of alveolar eosinophils (mean: 31.1 +/- 9.9%; range 6-66%). In two patients evaluation of alveolar eosinophil subpopulations showed a low percentage (27 and 36%) of hypodense cells, when compared to the high levels (> 80%) found in CEP. No significant correlation could be established between bronchoalveolar (BAL) results and clinical data, pulmonary function abnormalities, or biological results. Sequential evaluation of alveolitis in two AGA patients undergoing corticosteroid therapy demonstrated persistent alveolar eosinophilia, despite disappearance of clinical, radiological and biological abnormalities. Our data demonstrate that eosinophils are present in the alveolar spaces of patients with AGA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472833 TI - Gastrin-releasing peptide-like immunoreactive substance in bronchoalveolar lavage of idiopathic pulmonary fibrosis and sarcoidosis. AB - The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF. PMID- 8472834 TI - Nonadrenergic, noncholinergic responses stabilize smooth muscle tone, with and without parasympathetic activation, in guinea-pig isolated airways. AB - In guinea-pig isolated airways, nonadrenergic, noncholinergic (NANC) neural responses converge towards a similar level of smooth muscle tone, via a contraction when the tone is low prior to stimulation, and via a relaxation when the tone is high prior to stimulation. We wanted to assess the effect of simultaneous parasympathetic activation on these converging NANC responses, with and without the addition of sympathetic activation. In guinea-pig isolated airways, the spontaneous airway tone was initially abolished by indomethacin (10 microM). In one series, adrenergic depletion by guanethidine (10 microM) was then established, with and without cholinergic blockade by atropine (1 microM). In another series, either cholinergic blockade by atropine (1 microM) or no blockade was utilized. Responses to electrical field stimulation (1,200 mA, 0.5 ms, 3 Hz for 240 s) were studied with no induced tone, at a moderate (0.3 microM) and at a near-maximum (6 microM), histamine-induced tone. The mean level of the tonus equilibrium (% of maximum tone) was higher with the simultaneous NANC and parasympathetic activation than with NANC activation alone (75% compared with 44%, in the main bronchus, n = 8). The level of the tonus equilibrium was also higher with the simultaneous NANC, sympathetic and parasympathetic activation than with NANC and sympathetic activation only (49% compared with 21%, in the main bronchus, n = 8). The pattern was similar in the distal trachea. In conclusion, NANC neural responses can stabilize smooth muscle tone, and this stabilizing effect can be modulated by both parasympathetic and sympathetic activation, in guinea-pig isolated airways. PMID- 8472835 TI - Protection by N-acetylcysteine against pulmonary endothelial cell damage induced by oxidant injury. AB - The protective effect of N-acetylcysteine (NAC) against oxidant lung injury was investigated in a model of acute immunological alveolitis in the rat. Intrapulmonary immune complex deposition into rat lungs, induced by intratracheal infusion of immunoglobulin G (IgG) anti-bovine serum albumin (BSA) antibodies and intravenous injection of the antigen, caused lung damage associated with a marked decrease in [14C]5-hydroxytryptamine ([14C]5HT) uptake capacity, taken as a biochemical marker of endothelial cell function. The oral administration of a single dose of NAC (2 mmol.kg-1) 60 min before antigen/antibody (Ag/Ab) treatment was effective in preventing pulmonary endothelial cell [14C]5HT uptake loss induced by immune complex deposition. The mechanisms involved in this lung protective action of NAC were investigated by studying the antioxidant activity of NAC on hypoxanthine/xanthine oxidase-induced lung damage in vitro, and the effectiveness of the drug as lung glutathione (reduced form) (GSH) precursor in diethylmaleate-depleted rats. The results obtained provide further evidence on the ability of NAC to reduce the susceptibility of lung tissue to free radical induced damage, by potentiating the antioxidant defence systems. PMID- 8472836 TI - Occupational asthma due to zinc. AB - We describe a subject who developed asthma symptoms 2 yrs after being employed at a plant where metals were galvanized in heated zinc. The subject was not atopic. Baseline spirometry was normal three months after he left work but there was mild bronchial hyperresponsiveness to methacholine. Monitoring of forced expiratory volume in one second (FEV1) during a day at work showed a maximum fall in FEV1 of 24% at the end of the day and an increase in bronchial responsiveness on the following day. Environmental monitoring revealed that zinc and iron were present in the working environment at concentrations that were lower than the "threshold limit value-short term exposure level" (TLV-STEL) standards. Positive immediate skin tests to zinc sulphate at concentrations of 1 and 10 mg.ml-1 were obtained, although no specific immunoglobulin E (IgE) antibodies to zinc could be found. Skin tests with copper, chromium and cobalt were negative. Specific inhalation challenges were performed, having the subject inhale a solution of zinc sulphate at a 10 mg.ml-1 concentration for 6 min. An immediate reaction was elicited (maximum fall in FEV1 of 23%). We conclude that zinc can cause occupational asthma. PMID- 8472837 TI - [Short-term effectiveness of fissure sealants]. AB - Fluoride therapy is a widely accepted method of reducing smooth surface caries. Sealant therapy is intended to provide similar results for the occlusal surfaces of the teeth. In this study the retention of sealants was examined and a comparison was made between the caries rate in the group with sealed molars and controls after 12 months... The caries increment was significantly lower in the sealed group. PMID- 8472838 TI - [The effect of rare earth metal-containing toothpastes on dental enamel solubility in vitro]. AB - The effect of different REE containing toothpastes has been studied on human dental enamel, in an experimental model, using diluted suspensions of toothpastes. The grade of remineralization has been characterised by the amount of dissolved phosphorus from the enamel samples. All the investigated-, REE containing toothpastes decreased the acid-solubility of dental enamel, the best results were found in the group of samarium-containing toothpastes. PMID- 8472839 TI - [Computerized data base for recording information on patients with hypersensitivity to metals]. AB - The authors describe a computer analysable etiological card used for registration of data of Ni hypersensitive patients' with oral symptoms. The collection and evaluation of the data related to the pathological changes and predisposing factors can be useful in prevention of development of hypersensitivity or clinical symptoms of hypersensitivity in cases belonging to this risk group. PMID- 8472840 TI - Mechanisms of prolactin receptor regulation in mammary gland. PMID- 8472841 TI - Follistatins: more than follicle-stimulating hormone suppressing proteins. PMID- 8472842 TI - High level expression of human neuropeptide Y receptors in mammalian cells infected with a recombinant vaccinia virus. AB - Neuropeptide Y (NPY) is a 36 amino acid peptide present in the central and peripheral nervous system. Numerous studies point to a role of NPY in cardiovascular regulation. NPY effects are mediated through stimulation of specific cell surface G protein-coupled receptors. To allow biochemical studies of the receptor and of its interaction with the ligand, we have developed a potent expression system for NPY receptors using a recombinant vaccinia virus. A human NPY receptor cDNA was fused to a strong vaccinia virus promoter and inserted into the viral genome by homologous recombination. Recombinant viruses were isolated and tested for their ability to induce NPY binding site expression following infection of mammalian cell lines. Using saturation and competition binding experiments we measured a Bmax of 5-10 x 10(6) NPY binding sites per cell. The Kd for the binding of NPY is about 20 nM. Labelling of infected cells with a fluorochrome-labelled NPY indicated that the recombinant protein integrates into the cell membrane. PMID- 8472843 TI - Regulation of thyroid hormone receptor beta-2 mRNA levels by retinoic acid. AB - The thyroid hormone receptor, TR beta-2, whose expression is limited to the pituitary and parts of the central nervous system, is strongly negatively regulated at the pre-translational level by thyroid hormone (T3). We have investigated whether retinoic acid (RA), whose receptors (RARs) share a high degree of homology with the thyroid hormone receptors (TRs), can regulate this gene in a manner similar to T3, as has been shown for the growth hormone (GH) gene. GH3 cells were incubated with 10 nM T3, 1 microM RA or both for 48 h and then TR beta-2 mRNA levels determined by RNA blot hybridization analysis. We observed a 73% decrease in TR beta-2 mRNA levels after incubation with T3 and a two-fold increase in TR beta-2 mRNA levels after incubation with RA alone. In the presence of RA, the T3 effect on TR beta-2 mRNA levels was blunted with mRNA levels decreasing by only 20%. We investigated the mechanism by which retinoic acid increases and opposes the effects of T3 on levels of TR beta-2 mRNA. In transient transfection experiments using a reporter plasmid containing the TR beta-2 promoter and in nuclear run on assays, we found no effect of RA on TR beta 2 gene transcription. We then investigated whether the effects of RA were mediated at the post-transcriptional level. Determination of the apparent half life of TR beta-2 mRNA using the transcriptional inhibitor, actinomycin D, showed that RA had no effect on TR beta-2 mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472844 TI - Progesterone modulation of gonadotropin secretion by dispersed rat pituitary cells in culture. IV. Follicle-stimulating hormone synthesis and release. AB - Estradiol-treated, rat pituitary cells were studied to examine the effects of progesterone (P) on follicle-stimulating hormone (FSH) synthesis and secretion. Progesterone was administered prior to or concurrent with 3 h secretory challenges with either gonadotropin-releasing hormone (GnRH), the iontophore A23187, the protein kinase C activator phorbol 12,13-myristate (PMA), or no secretagogue. Medium FSH levels and cell FSH stores were quantified by radioimmunoassay and bioassay. Acute (< 6 h) exposures to P increased medium levels of immunoreactive and bioactive FSH following GnRH challenge without influencing total (cell + medium) values whereas chronic (9-24 h) treatments increased both parameters. Chronic P elevated total FSH levels even when no secretagogue was present. Studies with antiprogestins, 5 alpha dihydroprogesterone and 5 alpha-reductase inhibitors revealed that this direct action of P depended on progestin receptor occupation but not on 5 alpha reduction. These studies indicate that P selectively increases bioactive and immunoactive FSH levels, presumably by increasing FSH synthesis, and characterize the time course and cellular mechanisms of this response. To accommodate for P modulation of total FSH levels, FSH secretion was standardized as the percentage of cellular stores available for release. Progesterone modulation of GnRH stimulated FSH secretion was multiphasic, i.e. increased at 0-6 h, unchanged at 9 h and suppressed at 24 h. Acute and chronic exposures to P similarly modulated A23187-stimulated FSH release, whereas both P treatments increased PMA-stimulated FSH secretion. In these experiments P modulated luteinizing hormone secretion in parallel fashion, suggesting that common cellular mechanisms underlie peptidergic and steroidal regulation of the secretion of both gonadotropins. PMID- 8472845 TI - Efficient amidation of C-peptide deleted NPY precursors by non-endocrine cells is affected by the presence of Lys-Arg at the C-terminus. AB - Post-translational processing of peptide precursors producing amidated, biologically active peptides generally occurs in specially differentiated endocrine or neural cells. However, we have previously shown that a C-peptide deleted precursor of neuropeptide Y (NPY1-39) in which the precursor terminates in the sequence Gly-Lys-Arg was partially amidated by the non-endocrine cell line, CHO. In the present study we show that two other non-endocrine cell lines, NIH 3T3 and BHK, also possess amidating activities and that the NPY1-39 precursor was completely converted to NPY1-36 amide by the NIH 3T3 cell line. The role of the two basic residues (Lys-Arg) in the C-terminus was studied by transfection of a construct encoding a NPY precursor terminating with glycine alone. Both the CHO and NIH 3T3 cell lines, transfected with this construct, secreted a significantly smaller fraction of NPY reactive material as amidated NPY compared to the fraction of amidated NPY secreted by the cells transfected with the NPY1-39 precursor. It is concluded that the capacity to perform C-terminal amidation appears to be a universal feature of eukaryotic cells and that the carboxypeptidase E-like enzyme influences the amidation process, beyond its known ability to remove the C-terminal basic residues. PMID- 8472846 TI - Insulin secretion without the participation of arachidonic acid. AB - In order to study the role of arachidonic acid (AA) in depolarization-induced insulin secretion rat insulinoma cells (RINm5F) were depleted of AA by cultivation in essential fatty acid-free medium. Within 2 weeks AA content of these cells was decreased to a non-detectable level as assessed by gas chromatography (GC). Different cell lines were obtained by supplementation of the defatted medium with oleic acid or the AA precursor linoleic acid (7 and 70 microM, each). The AA content varied in dependence from the precursor availability from 0 to about 14% of long chain fatty acids. Variation in AA content or the depletion of AA to a non-detectable level did not modulate insulin synthesis, basal and potassium-induced insulin release, cell growth (cell number and protein), membrane depolarization and increases in cytosolic Ca2+. In AA containing cells no eicosanoids was produced in the course of stimulated hormone release. The data suggest that in RINm5F cells release of AA and/or formation of oxidized metabolites from AA are not essential for functional integrity. PMID- 8472847 TI - Differential expression of human placental growth hormone variant and chorionic somatomammotropin genes in choriocarcinoma cells treated with methotrexate. AB - Chorionic somatomammotropin (hCS) genes (hCS-A and hCS-B) and the placental growth hormone variant (hGH-V) gene are expressed in the syncytiotrophoblast in vivo, and at low levels in cytotrophoblast-like choriocarcinoma (BeWo) cells. Treatment of choriocarcinoma cells with methotrexate (MTX) will induce a cell type intermediate between a cytotrophoblast and syncytiotrophoblast. After treatment with MTX, hCS/hGH-V mRNA levels were decreased in BeWo cells, and only hGH-V and minor hCS-A related transcripts of 1.6, 2.1 and 4.2 kilobases, termed hCS-A2, hCS-A3 and hCS-A4, respectively, were detected. By contrast, chorionic gonadotropin RNA levels were increased. This pattern of hCS/hGH-V expression resembles that observed when BeWo cells are grown in thyroid hormone (T3) depleted serum, where hGH-V/hCS RNA increases in response to T3. This increase is blunted by MTX treatment, but is not due to a decrease in number or affinity of T3 receptors. These data indicate that the hGH-V and hCS genes can be differentially regulated by MTX, and are consistent with MTX interfering with T3 responsiveness of these genes. Also, if BeWo cells treated with MTX do represent a transitional state, these data raise the possibility that hGH-V and hCS possess a different temporal pattern of expression in the developing trophoblast. PMID- 8472848 TI - An androgenic affinity ligand covalently binds to cytosolic aldehyde dehydrogenase from human genital skin fibroblasts. AB - A 56 kDa protein expressed in human genital skin fibroblasts was first identified by independent laboratories on the basis of its specific expression in androgen target cells and its ability to covalently bind androgenic affinity ligands. Recently, immunoscreening of a cDNA library with antisera directed against this protein resulted in the isolation of a partial cDNA clone identical to human cytosolic aldehyde dehydrogenase (ALDH1). We report here the preparation of a full-length cDNA encoding ALDH1 from human genital fibroblasts. Translation of the encoded protein in a cell-free system yields a 56 kDa product that can be covalently radiolabeled with [3H]dihydrotestosterone 17 beta-bromoacetate (DHT BA). Expression of the full-length clone in mammalian cells also results in expression of a 56 kDa DHT-BA binding protein. The covalent binding of DHT-BA by ALDH1 is an intrinsic property of the enzyme and is not dependent on androgen receptor expression. PMID- 8472849 TI - Platelet derived growth factor-A chain gene expression in cultured mesangial cells: regulation by phorbol ester at the level of mRNA abundance, transcription and mRNA stability. AB - In human renal mesangial cells, platelet derived growth factor (PDGF)-A chain is subject to regulation by protein kinase C (PKC) activator, phorbol ester (phorbol 12-myristate 13-acetate, PMA). Treatment of mesangial cells with PMA increases PDGF-A chain mRNA abundance as analyzed by Northern blot hybridization. In contrast to the effect of PMA, the inactive analog phorbol had no effect on PDGF A chain mRNA levels, while the PKC inhibitor H7 markedly reduced the PMA-induced increment in PDGF-A chain mRNA. To determine the mechanism by which PMA increases the abundance of this gene, transcription rate was measured by nuclear transcript elongation assay. Treatment of mesangial cells with PMA resulted in a 2-fold increase in PDGF-A chain gene transcription. In addition, we analyzed the effects of PMA on PDGF-A chain mRNA half-life as measured directly by pulse-chase method. PDGF-A chain mRNA has a half-life of about 106 min. The PDGF-A chain mRNA half life was reduced by 30% (t1/2 = 74 min) when mesangial cells were incubated with PMA. Our results demonstrate that in human renal mesangial cells, the regulation of PDGF-A chain gene expression by PMA is primarily at the level of transcription. PMID- 8472850 TI - Transcription rate of the follicle stimulating hormone (FSH) beta subunit gene is reduced by inhibin in sheep but this does not fully explain the decrease in mRNA. AB - Studies were conducted in vitro and in vivo to determine whether or not inhibin affects the transcription rate of the gene for the beta subunit of follicle stimulating hormone (FSH beta). Pituitary cells in primary culture were incubated with 0-3000 milli-units/ml inhibin; a dose-related decrement in mRNA was obtained but a parallel effect was not observed for the transcription rate of the FSH beta gene in a nuclear run-on experiment. To determine effects in vivo, ovariectomized ewes were treated with saline (group 1), 75 micrograms inhibin 6 h before slaughter (group 2), inhibin 6 h and 12 h before slaughter (group 3) or inhibin 12 h before slaughter (group 4). In samples taken each 2 h, plasma FSH levels were seen to be maximally reduced 6 h after a single injection of inhibin; at this time mRNA levels were reduced up to 100% whereas FSH beta gene transcription rate was reduced by 50%. A second injection at 6 h (group 3) caused a further reduction in plasma FSH levels with no additional effect on transcription rate. In those sheep killed 12 h after a single inhibin injection, transcription rate for the FSH beta gene, cytoplasmic mRNA levels and plasma FSH concentrations had recovered. These studies show that the rapid effect of inhibin on FSH beta mRNA levels may be due, in part, to an effect on transcription rate of the FSH beta gene. An additional mechanism is required, however, to fully explain the inhibin effect on FSH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472852 TI - High expression of the hormone binding active extracellular domain (1-294) of rat lutropin receptor in Escherichia coli. AB - Using the polymerase chain reaction (PCR) technique, the cDNA fragment corresponding to the receptor coding region for residues 1-294 was prepared from rat lutropin receptor (LHR) cDNA and subsequently subcloned into Escherichia coli expression vector pT7-7. This truncated receptor was efficiently expressed in E. coli as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. The recombinant protein present in the inclusion bodies was solubilized in 6 M guanidine-HCl and purified in two successive steps of fast performance liquid chromatography (FPLC) using Superose-12 and Mono Q columns. Refolding of the purified recombinant protein was achieved in 1.5 M guanidine-HCl in the presence of an equimolar proportion of cysteine and cystine. The refolded soluble truncated LHR(1-294) had apparent molecular weights of 33 kDa and 140 kDa under reducing and nonreducing conditions, respectively. The multimeric nature of the extracellular domain of the receptor is believed to be due to its self-association by intermolecular disulfide bond formation since the 1-294 amino acid segment has nine cysteine residues and thus has one or possibly more free sulfhydryl groups. The purified truncated receptor had high binding affinity for human choriogonadotropin (hCG) as indicated by ligand blotting on SDS-PAGE and radioligand receptor assays. The amount of hCG required for 50% inhibition of binding of 125I-hCG to the soluble truncated receptor was 2.7 x 10( 10) M (or 12.25 ng). Similarly, the amount of soluble truncated receptor required for 50% inhibition of 125I-hCG binding to the rat ovarian receptor in the radioligand receptor assay was 58 ng.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472851 TI - Effect of benzyl succinate on insulin receptor function and insulin action in skeletal muscle: further evidence for a lack of spare high-affinity insulin receptors. AB - Benzyl succinate inhibited insulin binding and tyrosine receptor kinase in a concentration-dependent manner in the partially purified insulin receptor preparation from rat skeletal muscle. Benzyl succinate lowered the apparent number of high-affinity insulin binding sites. We have made use of the inhibitory effect of benzyl succinate to investigate the possible presence of spare high affinity insulin receptors in muscle. Benzyl succinate inhibited the effect of a supramaximal concentration of insulin on 3-O-methylglucose uptake, 2 (methylamino)isobutyric acid uptake and lactate production by the incubated muscle. Furthermore, the inhibitory effect of benzyl succinate on insulin binding in vitro closely correlated with its inhibitory effect on insulin action in vivo. These findings suggest the absence of spare high-affinity insulin receptors in skeletal muscle. In contrast to data obtained in skeletal muscle, benzyl succinate did not affect the maximally insulin-stimulated glucose transport, although it caused a marked decrease in insulin sensitivity in isolated rat adipocytes, for which the existence of spare insulin receptors is well documented. PMID- 8472853 TI - Blockade of androstenedione-induced stimulation of androgen-sensitive parameters in the rat prostate by combination of Flutamide and 4-MA. AB - In order to mimic the human situation in which adrenal steroid precursors are converted to the active androgen dihydrotestosterone (DHT) in prostatic tissue, we have used castrated rats supplemented with the precursor steroid androstenedione (delta 4-dione) released from Silastic implants. While it is well known that the action of DHT can be partially neutralized by antiandrogens which compete for binding to the androgen receptor, we have used 17 beta-N,N diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), an inhibitor of 5 alpha-reductase, the enzyme which converts testosterone into DHT, in order to decrease intraprostatic DHT levels and thus facilitate the action of the antiandrogen. Animals were treated for 7 days with Flutamide (FLU, 2 mg) or 4-MA (4 mg) injected subcutaneously, twice daily, alone or in combination. 4-MA administered alone caused a 54% inhibition of delta 4-dione-stimulated ventral prostate weight while FLU exerted a 74% inhibitory effect and 4-MA+FLU further improved inhibition to 81%. We then measured, by in situ hybridization, the levels of prostatic mRNAs encoding the C1 and C3 components of the prostatic binding protein (PBP) which are highly specific and sensitive markers of androgen action. PBP-C3 mRNA levels fell by 95% following castration while treatment with delta 4-dione completely reversed the effect of castration. Administration of FLU or 4-MA independently caused 33% and 10% decreases, respectively, of PBP-C3 mRNA levels stimulated by delta 4-dione while the combination of both compounds further inhibited PBP-C3 mRNA levels to reach a 55% inhibition. Similar effects were observed on PBP-C1 mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472854 TI - Prostaglandin F2 alpha activates protein kinase C in human ovarian cells. AB - Recent studies in several non-primate species have suggested that prostaglandin F2 alpha (PGF2 alpha) inhibits luteal cell progesterone production by activating the calcium and phospholipid-dependent protein kinase, protein kinase C (PKC). This study investigated the presence of PKC in human ovarian cells and assessed the ability of PGF2 alpha and its structural analogue, cloprostenol, to generate inositol polyphosphates and activate PKC. PKC was detected in cultured human granulosa-lutein cells and human luteal cells (from mid-late luteal phase). The major proportion of PKC detected was cytosol-associated in both cell types. Cloprostenol increased the generation of inositol polyphosphates in cultured human granulosa-lutein cells in a dose- and time-dependent manner. In addition both cloprostenol and PGF2 alpha activated PKC (as assessed by redistribution of enzyme activity from a principally cytosol-associated form to a membrane associated form) in both granulosa-lutein and luteal cells. Short-term exposure of both cell types to phorbol myristate acetate (4 beta-PMA) activated PKC, whilst prolonged exposure of human granulosa-lutein cells to 4 beta-PMA led to a > 85% loss of total PKC activity. The inactive phorbol ester, 4 alpha-PMA, had no effect on PKC activity when exposed to cells for up to 20 h. These results demonstrate the presence of PKC in human ovarian cells and the ability of PGF2 alpha to induce translocation/activation of this kinase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472855 TI - Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor. AB - Recent studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is required for the induction of interstitial collagenase in cultured rat and human myometrial smooth muscle cells. The present study was performed to determine which serotonin receptor subtype mediates the induction of collagenase in these cells. [125I]DOI ((+/- )-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane), a 5-HT2 receptor agonist radioligand, bound specifically to sites in myometrial cell membranes, and exhibited binding characteristics essentially identical to those observed with brain 5-HT2 receptors. Radioligands selective for other serotonin receptor subtypes (5-HT1 and 5-HT3) failed to yield detectable binding. Northern blot analysis demonstrated the presence of 5-HT2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT1A and 5-HT1C receptors were not detectable. Moreover, RT-PCR indicated that 5-HT2 receptor mRNA is present in freshly isolated uterine tissue as well. Selective antagonists of the 5-HT2 receptor, ketanserin and spiperone, displayed concentration-dependent inhibition of serotonin-mediated collagenase induction in the myometrial cultures. These antagonists yielded IC50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT2 receptor-mediated response. In addition, a number of selective 5-HT2 receptor agonists (quipazine, alpha-methyl-serotonin, DOI) mimicked the ability of serotonin to induce collagenase production, whereas compounds selective for 5-HT1 and 5-HT3 receptor subtypes had little effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472856 TI - Effect of thyroid hormone on T3-receptor mRNA levels and growth of thyrotropic tumors. AB - Thyrotropic tumors (TtT97) contain mRNA transcripts for three T3-receptor (TR) isoforms, alpha 1, beta 1 and beta 2, and a non-receptor alpha 2-variant. We administered T4 (5 mg/l of drinking water) for one month to TtT97-bearing mice, to examine its effect on tumor growth and tumor TR isoform steady-state mRNA levels. Baseline mice were killed at the start of the experiment, and placebo mice were maintained hypothyroid. The treated tumors were 30-35% smaller than the baseline tumors (p = NS), while the placebo tumors were 2- to 7-fold larger than the baseline tumors (p < 0.05). TR beta 1 mRNA increased 5- to 6-fold, while TR beta 2 mRNA decreased by 76%. TR alpha 1 and the alpha 2-variant decreased by 52% and 70%, respectively. Therefore, the tumors decreased their growth rate in response to T4 administration, and increased the ratio of TR beta 1 to TR beta 2 mRNA. This raises the intriguing possibility of a correlation between the relative abundance of the TR beta isoforms and tumor growth. PMID- 8472857 TI - C-myc gene chromatin of estrogen receptor positive and negative breast cancer cells. AB - Expression of the c-myc protooncogene is estrogen regulated in estrogen receptor (ER) positive, hormone-dependent human breast cancer cells, but it is constitutively active in ER negative, hormone-independent breast cancer cells. To determine whether these differences are reflected in c-myc chromatin, DNase I hypersensitive sites (DHS) were mapped. Six DHS were detected in all cell lines studied, with DHS 3(2) being more prominent than DHS 3(1). The accessibility of DHS 2 was markedly greater in ER negative cells than in ER positive cells, and this relative accessibility remained unchanged when cells were grown in estrogen free medium. DHS 2, 3(1) and 3(2) map near the P0, P1 and P2 promoters, respectively. An analysis of promoter usage demonstrated that P2 was the preferred promoter. Thus, the differences in the accessibility of DHS 2 in c-myc chromatin of ER positive and negative cells likely reflects alterations in DNA protein interactions in this region. PMID- 8472858 TI - Vanadate treatment of diabetic rats reverses the impaired expression of genes involved in hepatic glucose metabolism: effects on glycolytic and gluconeogenic enzymes, and on glucose transporter GLUT2. AB - The trace element vanadium is a potent insulinomimetic agent in vitro. Oral administration of vanadate to rats made diabetic by streptozotocin (45 mg/kg i.v.) caused a 65% fall in plasma glucose levels without modifying low insulinemia. We studied whether the hypoglycemic effect of vanadate was associated with altered expression of genes involved in key steps of hepatic glucose metabolism. Glucokinase (GK) and L-type pyruvate kinase (L-PK) mRNA levels were decreased respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of vanadate treatment partially restored GK mRNA and activity (40% of control levels), and totally restored L-PK parameters. In contrast to the glycolytic enzymes, mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were increased (15- and 2-fold, respectively) in fed diabetic rats. Vanadate treatment normalized both PEPCK mRNA and activity in diabetic rat liver. The 2-fold increase in liver glucose transporter (GLUT2) mRNA and protein, produced by diabetes, was also corrected by this treatment. In conclusion, oral vanadate given to diabetic rats induces a shift of the predominating gluconeogenic flux, with subsequent high hepatic glucose production, into a glycolytic flux by pretranslational regulatory mechanisms. PMID- 8472859 TI - Pituitary as a target organ for toxic effects of P4501A1 inducing chemicals. AB - We report here that cytochrome P4501A1 in the male rainbow trout pituitary is highly inducible by beta-naphthoflavone. Pituitary cells containing inducible P4501A1 were identified by double immunostaining as gonadotrophs containing gonadotropin II. Thus, the pituitary gonadotrophs may be target cells for polyaromatic hydrocarbons. Elevated plasma levels of gonadotropin II (GTH II) and testosterone in the induced fish indicated that the functioning of the pituitary was disturbed. Because GTH II regulate the final stage of sexual maturation the results implies that exposure to P4501A1 inducing compounds may disturb this development stage. PMID- 8472860 TI - What is the function of circulating insulin-like growth factor-2 in postnatal life? PMID- 8472861 TI - In situ hybridization for creatine kinase-B messenger RNA in rat uterus and brain. AB - Creatine kinase-B (CKB) is present in both uterus and brain, and in uterus its synthesis (protein and mRNA) is regulated by estrogen. In the present study we have used in situ hybridization to detect CKB mRNA in uterus and brain, and to determine whether there is cell type specific induction of CKB by estrogen in these tissues. Tissue was taken from ovariectomized (ovx) rats that had been injected with either estrogen (17 beta-estradiol-3-benzoate and/or 17 beta estradiol) or vehicle alone, 2, 8, 24 and 72 h previously. The brains and uteri were removed, frozen, cryostat-sectioned, and processed for in situ hybridization histochemistry. The uterine and brain sections were incubated with a tritiated DNA probe complementary to a 3' fragment of CKB mRNA, or a control sense probe to the same 3' fragment. In uterine smooth muscle cells, a 2.5- and 3.5-fold induction of CKB mRNA was observed 2 and 24 h after estrogen administration, respectively, and levels approached ovx controls at 72 h. A smaller induction (1.9-fold, 2 h) was observed in uterine epithelium, with little induction of CKB mRNA in stroma. In the brain CKB mRNA was detected in neurons, but not in clearly identified glia, and only occasionally in ependymal cells. In brain regions containing estrogen receptors there was no evidence of a significant estrogen effect on CKB mRNA levels. Some brain regions had higher neuronal expression than others (e.g. medial septum vs. preoptic area), but expression was widespread and not limited to neuroendocrine sites. PMID- 8472862 TI - Biphasic effect of basic fibroblast growth factor on 125I-human chorionic gonadotropin binding to cultured immature Leydig cells. AB - The present studies examined the effects of basic fibroblast growth factor (bFGF or FGF-2) on 125I-human chorionic gonadotropin (hCG) binding to cultured immature rat Leydig cells. We found that low concentrations of bFGF (0.1-1.0 ng/ml) inhibited 125I-hCG binding to cultured immature Leydig cells in a dose- and time dependent manner; however, this inhibition was reversed partially at higher bFGF concentrations (10-200 ng/ml). The decline in 125I-hCG binding by bFGF was due to a reduction in the number of binding sites per cell and not to a change in receptor affinity for the ligand. The inclusion of 10 micrograms/ml heparin (a concentration that is reported to block bFGF binding to heparan sulfate proteoglycans) with increasing bFGF concentrations had no effect on the inhibition of 125I-hCG binding by low bFGF concentrations, but completely blocked the secondary increase in binding by higher bFGF concentrations. In addition, neither varying heparin concentrations (0.1-25 micrograms/ml) nor insulin or insulin-like growth factor-I had any effect on the inhibition of 125I-hCG binding by 1 ng/ml bFGF. These studies suggest that receptor-mediated actions of bFGF (inhibition of hCG binding by low bFGF concentrations) on cultured immature Leydig cells are unaffected by heparin; however, the secondary increase in 125I hCG binding observed with higher bFGF concentrations (mediated by bFGF binding to heparan sulfate proteoglycans) is blocked by heparin. PMID- 8472863 TI - Effect of various protein kinase inhibitors on the induction of milk protein gene expression by prolactin. AB - Prolactin has many known functions and one of them is to induce the expression of milk protein gene expression in the mammary gland. Specific membrane receptors have been recently characterized but the transduction mechanism involved in the transfer of the prolactin signal to milk protein genes remains unknown. In the present work, it is shown that several protein kinase inhibitors block prolactin action on milk protein genes. Primary rabbit mammary cells were cultured for several days on floating collagen gel in a serum-free medium. Prolactin and the inhibitors of protein kinase were then added to the culture medium. After 1 day, the concentration of alpha s1-casein in the culture medium was measured using a specific radioimmunoassay. The concentration of several mRNAs in cell extracts was also evaluated using Northern blot analysis. alpha s1-Casein secretion and alpha s1-casein mRNA accumulation were induced by prolactin. This induction was blocked by staurosporine, sphingosine, quercetin, genistein and to some extent by o-hydroxyphenyl acetate, but not by H7, polymyxin B, benzylsuccinate and lavendustin A. The concentration of the mRNA coding for transferrin, which is abundantly secreted in rabbit milk independently of prolactin action, was only moderately altered by the inhibitors. The concentration of two house-keeping mRNAs, beta-actin and glyceraldehyde 3-phosphate dehydrogenase, was lowered only by genistein after 1 day but not after 4 h of culture. These data show for the first time that a Ser/Thre kinase, which is not kinase C, and possibly a tyrosine kinase is involved in the transduction of the prolactin message from the receptor to the milk protein genes. PMID- 8472864 TI - Fuel secretagogue stimulation of arachidonic acid accumulation in fresh and cultured pancreatic islets. AB - It has been previously demonstrated that glucose stimulation of islets of Langerhans causes an accumulation of unesterified arachidonic acid that correlates with insulin secretion. In addition, it is well established that glucose metabolism is essential for insulin secretion. We show that non metabolizable analogs of glucose which do not stimulate insulin secretion fail to cause significant accumulation of unesterified arachidonic acid. In addition, mannoheptulose, an inhibitor of glucose metabolism, completely blocks the glucose induced increase in arachidonic acid accumulation. Among the nutrient secretagogues tested, only alpha-ketoisocaproic acid causes a significant increase in unesterified arachidonic acid accumulation. Mannose, fructose, and glyceraldehyde, in particular, failed to elicit a significant increase in unesterified arachidonic acid accumulation. Our data, taken together with previous studies, suggests that glucose must be metabolized to induce accumulation of unesterified arachidonic acid in pancreatic islets. PMID- 8472865 TI - Insulin receptor beta-subunit serine phosphorylation in permeabilized cultured fetal rat hepatocytes. AB - Regulation of cellular protein phosphorylation by insulin was investigated after short exposure at 37 degrees C prior to applying the permeabilization/phosphorylation step in the presence of digitonin and [gamma 32P]ATP for 30 min at 4 degrees C. The results revealed major 32P incorporation into a limited number of membrane polypeptides exhibiting a molecular mass of 95, 58 and 51 kDa. Phosphorylation of 95 kDa protein was selectively inhibited with Ca(2+)-free EGTA-containing permeabilization/phosphorylation buffer and became predominant in the presence of Ca2+. Considering in particular its immunoprecipitation by a monoclonal antibody directed against insulin receptor, the 32P-labeled 95 kDa protein represented the beta-subunit of the insulin receptor. Its phosphorylation was transiently stimulated after exposure to insulin (35% after 2 min), and concerned mostly serine residues under both basal and stimulated conditions. Vanadate had a similar effect and both agents favored glycogenesis, whereas heparin which inhibited 95 kDa protein phosphoseryl phosphorylation had an opposite effect on glycogenesis. These results suggest a biological role for the membrane-associated phosphoseryl-protein kinase(s) and phosphatase(s) acting on the insulin receptor beta-subunit in cultured fetal hepatocytes. PMID- 8472866 TI - Effect of epidermal growth factor/transforming growth factor alpha on lactate production in porcine Sertoli cells: glucose transport and lactate dehydrogenase isozymes as potential sites of action. AB - Germ cell development is dependent upon the delivery of essential nutriments such as lactate originating from Sertoli cells. Lactate production is under the systemic control but probably also under a local control exerted via certain growth factors. By using a model of porcine cultured Sertoli cells, we have characterized the action of epidermal growth factor (EGF) on lactate production and further delineated the potential biochemical mechanisms involved in the EGF action. EGF stimulated lactate production in a time and dose dependent manner with a half-maximal (ED50) and maximal effects, respectively with 3.8 (0.6 x 10( 9) M) and 22 ng/ml of EGF. Lactate formation involves several biochemical steps among which the glucose substrate uptake and transport system as well as the lactate dehydrogenase (LDH) activity appear to play key roles. We report here that EGF increased the uptake of glucose evaluated through that of 2-deoxy-D glucose (2-DOG), a non-metabolizable glucose analog. Such an increase in glucose substrate uptake occurs both after a long term (48 h) and a short term treatment (ED50 = 6.4 ng/ml, 1.1 x 10(-9) M EGF). Moreover, EGF was also able to enhance the activity of the Sertoli cell LDH. The maximal effect of the growth factor on LDH activity was observed after a long term (24 h) treatment with an ED50 of 7 ng/ml (1.2 x 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472867 TI - Transforming growth factor beta stimulation of parathyroid hormone-related protein (PTHrP): a paracrine regulator? AB - The regulation of PTHrP expression and production by transforming growth factor beta (TGF beta) has been investigated in an epidermal squamous cancer cell line COLO 16. TGF beta 1 treatment increased steady-state levels of PTHrP mRNA and concentrations of PTHrP immunoreactivity in conditioned medium in a time- and dose-dependent manner with a half-maximal effect at 40 pM. An effect of TGF beta 1 on PTHrP mRNA was observed first after 4 h treatment and continued to increase up to 48 h with a concomitant increase in PTHrP immunoreactivity in the culture medium. TGF beta 1 was found to stabilize PTHrP mRNA as assessed by actinomycin C1 experiments. In addition, a direct effect of TGF beta to increase PTHrP transcription was indicated by nuclear run-on and transient transfection experiments using a CAT promoter/expression construct encompassing the region 1100 bp to -20 bp from the initiating AUG of the human PTHrP gene. The conditioned medium from COLO 16 cells was also shown to contain both latent and active TGF beta at concentrations of 160 pM and 16 pM, respectively, in 72 h conditioned medium. A neutralizing antibody to TGF beta 1 (and TGF beta 2) decreased the level of immunoassayable PTHrP in the medium. PMID- 8472868 TI - Dopamine regulates D2 receptor gene expression in normal but not in tumorous rat pituitary cells. AB - Abnormalities of dopamine D2 receptors may be implicated in the development of some pituitary tumours. Previously we have identified dopamine D2 receptor gene expression both in normal rat pituitaries and in dopamine resistant GH3 rat pituitary tumour cells. In this study we have examined the effect of dopamine on D2 receptor gene expression in these cells using a probe specific for both D2 receptor isoforms. Normal rat pituitary cells were maximally stimulated by 100 nM dopamine at which concentration D2 receptor mRNA concentrations were 400% greater than that measured in controls. No increase in D2 receptor gene expression was observed in GH3 pituitary tumour cells. PMID- 8472869 TI - Influence of hormones on tumor growth, cell kinetics, estrogen receptor and insulin-like growth factor-I-related protein of human breast cancer (MCF-7) cells transplanted in nude mice. AB - The influence of estrogens and tamoxifen on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells transplanted into athymic nude mice was investigated. The mice were divided into the following three groups: (1) an E2 group with mice receiving 17 beta-estradiol dipropionate; (2) a TAM group with mice receiving tamoxifen; (3) a control group with mice given no hormone. (1) Tumor growth was significantly increased in the E2 group, but significantly decreased in the TAM group compared to control; (2) the tumor contents of insulin-like growth factor-I (IGF-I) and the rate of IGF-I-positive cells were significantly lower in the E2 group, but significantly higher in the TAM groups compared to control; (3) the IGF-I-positive cell rates were in significant inverse correlation with the [3H]thymidine-labeled cell rates in the E2, TAM and control groups. Thus, the tumor contents of IGF-I and the rate of IGF-I-positive cells were inversely correlated to the tumor growth and the [3H]thymidine-labeled cell rate in this in vivo study, although IGF-I is known to be a mitogen for breast cancer cells in vitro. Further studies are necessary to answer the questions as to the in vivo roles of immunoreactive IGF-I in ER-positive breast cancer. PMID- 8472870 TI - Autoimmune T-cell recognition sites of human thyrotropin receptor in Graves' disease. AB - Five overlapping synthetic peptides representing two regions of thyrotropin (TSH) binding sites of human thyrotropin receptor (TSHR) (peptides 12-30, 24-44, 308 328, 324-344 and 339-364) were investigated for their ability to cause proliferation of peripheral blood lymphocytes (PBL) from eight patients with Graves' disease. The same experiment was done using PBL from four cases with Hashimoto's thyroiditis, two cases with subacute thyroiditis, two cases with rheumatoid arthritis (RA) and eight normal volunteers. PBL obtained from each patient with Graves' disease responded to one or more of peptides 12-30, 24-44, 308-328 and 324-344, while peptide 339-364 had no stimulating activity. The level of stimulating activity of each of the four aforementioned TSHR peptides varied from patient to patient. None of the five TSHR peptides caused the proliferation of PBL from patients with Hashimoto's thyroiditis, subacute thyroiditis, or RA and from normal volunteers. The results indicate that the proliferation of PBL by TSHR peptides is specific in patients with Graves' disease and that the regions of TSHR which are involved in the binding to TSH are also the target of autoimmune T-cell recognition in Graves' disease. The difference in T-cell response from patient to patient could be explained by genetic regulation toward each autodeterminant. PMID- 8472871 TI - Cytotoxic activity of lutropin-gelonin conjugate in mouse Leydig tumor cells: potentiation of the hormonotoxin activity by different drugs. AB - A hormonotoxin preparation composed of gelonin, a basic protein of 30,000 Da isolated from the plant Gelonium multiflorum and the luteinizing hormone (LH, lutropin) isolated from the sheep pituitary has been studied for its cytotoxic action on mouse testicular Leydig tumor cells (MA-10 cells). Gelonin modified with 2-iminothiolane and conjugated with hormone modified by N-succinimidyl-3-2 pyridyl dithiopropionate was able to inhibit protein synthesis in Leydig tumor cells. An enhancement of the cytotoxicity of the hormonotoxin was obtained in the presence of drugs like quinacrine, chloroquine, verapamil and monensin. We report that the cytotoxicity of hormonotoxin was enhanced 10-15 times with quinacrine (7.6 microM), chloroquine (29 microM), verapamil (40 microM) and monensin (0.29 microM). While quinacrine, chloroquine and verapamil were not cytotoxic to MA-10 cells for up to 48 h, monensin alone reduced protein synthesis significantly in 48 h. All the drugs studied here inhibited steroidogenic action of the native hormone even at concentrations which were not detrimental to protein synthesis. On the basis of the above studies, we suggest that it may be feasible to develop combination strategies to destroy gonadal cells bearing gonadotropin (LH) receptors. In cells not bearing LH receptors (COS-7 cell line) there was no cytotoxicity either with hormonotoxin alone or in combination with the drugs, suggesting specificity of action. PMID- 8472872 TI - Osmotic stimuli attenuate vasoactive intestinal peptide gene expression in the rat anterior pituitary gland. AB - Studies on vasoactive intestinal peptide (VIP) in the anterior pituitary gland have shown that it is synthesized locally, physiologically regulated, and may act as a paracrine/autocrine factor. We have now investigated the regulation of anterior pituitary VIP gene expression in rats during osmotic stimulation. Both salt-loading and dehydration resulted in a progressive and marked reduction in VIP mRNA levels as determined by Northern analysis, to 10% of control levels at 14 days of salt-loading. The 1.7 and 1.0 kb VIP RNA transcripts were equally affected. Since anterior pituitary VIP is partially localized in lactotrophs we also measured prolactin (PRL) mRNA levels. In contrast to VIP, PRL mRNA levels were increased during both osmotic paradigms, the mRNA levels being significantly raised after 5 days of salt-loading to 130% of controls. Further experiments, conducted to examine the mechanism by which VIP gene expression is down-regulated during osmotic stimulation, demonstrated that dopamine and angiotensin II do not appear to be involved. The results show dissociated regulation of VIP and PRL during osmotic stimulation and provide suggestive evidence of a role for anterior pituitary VIP in the animal's osmoregulatory responses. VIP may therefore be a paracrine factor with diverse functional roles. PMID- 8472874 TI - American Diabetes Association. 53rd annual meeting. June 12-15, 1993. Abstracts. PMID- 8472873 TI - Structural and functional characterization of the rat follistatin (activin binding protein) gene promoter. AB - Follistatin was originally identified as a specific inhibitor of follicle stimulating hormone secretion and later characterized as a binding protein for activin. Since activin regulates hormone secretion and cell differentiation, the importance of understanding the mechanisms regulating the synthesis of its binding protein, follistatin, is evident. To study the regulation of follistatin gene expression, we first determined the transcription start site (cap site) of the rat follistatin gene using primer extension and ribonuclease protection assay. Our results led to the identification of multiple cap sites located at three different positions of the promoter. DNA sequence analysis revealed that each cap site was located at approximately 30 nucleotide (nt) downstream of three distinct TATA-like sequences. In primary cultures of rat granulosa cells, transfection studies using 5'-flanking regions of follistatin gene fused to the chloramphenicol acetyltransferase (CAT) reporter gene revealed the presence of two DNA segments that act to suppress basal transcriptional activity. The promoter activity of the CAT construct containing 2.6 kilo base pairs (kb) of 5' flanking region was induced 2.5-fold above basal activity by forskolin (10 microM), and 1.6-fold by 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nM). Co treatment with forskolin and TPA resulted in a 6.4-fold induction in its promoter activity, suggesting that two distinct signal transduction pathways, the cAMP dependent protein kinase-A pathway and diacylglycerol-dependent protein kinase-C pathway, act coordinately to modulate follistatin gene transcription. Experiments using a series of 5'-flanking region deletion constructs located the regulatory regions responsive to these two pharmacological agents at nt -312 to -32 and -35 to +139. PMID- 8472875 TI - Speech spectra for six recorded monosyllabic word tests. AB - Speech spectra (long-term RMS levels and 1% speech peaks) in third-octave bands were determined for six monosyllabic word test materials: digital recordings of the Central Institute for the Deaf W-22 word test and the Northwestern University NU-6 word test obtained from Qualitone; audiotape recordings of the Central Institute for the Deaf W-22 word test, the Northwestern University NU-6 word test, and the Harvard Psycho-Acoustic Laboratory PB-50 word test obtained from Auditec of St. Louis; and an audio-tape recording of the Maryland CNC word test obtained from Olsen Distributors. The spectra were generally within 2 SD of previous results for continuous speech spoken by an average male talker (Cox, Matesich, & Moore, 1988; Cox & Moore, 1988), but differed sufficiently from those data and from one another to affect the accuracy of Articulation Index calculations. The relationship between the level of the calibration tone and the speech in the third-octave band centered at 1000 Hz was different for each recording. PMID- 8472876 TI - The effect of listeners' experience on the evaluation of intonation contours produced by hearing-impaired children. AB - This study investigated the effect of the listener's experience on the evaluation of intonation contours produced by hearing-impaired children. Stimuli included imitations of intonation (based on synthetic speech stimuli) produced by hearing impaired children. Twenty listeners (10 experienced and 10 naive) evaluated the intonation production by means of two evaluation tools: a rating scale and a forced-choice test. No significant differences were found between the two listener groups using the forced-choice test, either for the falling or for the rising contours. However, a significant difference was found between the two listener groups using the rating scale, with regard to both the rising and the falling contours. Thus, the effect of experience decreased when using the forced choice procedure. This finding supports the use of the forced-choice method for providing a perceptual measure of speech production performance that is independent of the listener's experience. PMID- 8472877 TI - Factors in the development of a training program for use with tactile devices. AB - A review of the literature suggests that, in order to maximize the benefits available through a tactile device, it must be accompanied by an effective and adaptive training program. There are a number of factors to consider in the design of such a training program, including the type of tasks and response formats to include, the amount of training, subject motivation and device use, the characteristics of the potential user population, the specific device to be used and the type of information it provides, and the evaluation procedures to be followed. The type and saliency of the information provided by a particular tactile device are highlighted as the most important yet neglected consideration in designing a training program. The training program used with the University of Melbourne's multiple-channel electrotactile device is presented to show how these important factors may be addressed, to indicate the flexibility required in a training program, and to provide a general framework on which researchers may base the development of programs for other tactile devices. PMID- 8472878 TI - Development of a hearing test protocol for profoundly involved multi-handicapped children. AB - The purpose of the present study was to develop a protocol for use in testing the hearing of profoundly involved multi-handicapped children. Behavioral observation audiometry, visual reinforcement audiometry, auditory brain stem response (ABR), and noise-tone-difference tests were administered to 156 children with multiple handicaps. Eighty-three percent of the children with normal middle ear function were estimated to have normal hearing or, at worst, a mild hearing loss, by one or more of the tests. ABR was the single best test, followed by behavioral observation audiometry and noise-tone-difference. However, only 65% of the children would have passed had they only been tested with ABR. If agreement among two of the tests had been required, hearing loss would have been ruled out in only 34% of the children. A factor analysis revealed that the various hearing tests were associated with different medical and physical conditions which might influence threshold estimation for multi-handicapped children. These results support use of a series-positive test battery protocol in which individual tests are used sequentially with the purpose of ruling out moderate-profound sensorineural hearing loss. PMID- 8472879 TI - Click-evoked otoacoustic emissions and hearing threshold in sensorineural hearing loss. AB - The influence of hearing loss on the click-evoked otoacoustic emissions (EOAE) were studied in 931 ears. The EOAEs were never found when hearing loss on the best hearing frequency was above 40 dB HL. The presence of EOAEs reflects the hearing threshold at the best hearing frequency, not only at the middle frequencies. PMID- 8472880 TI - Experimental design for hearing aid research. PMID- 8472881 TI - Improving the reliability of the auditory middle latency response by monitoring EEG delta activity. AB - The auditory middle latency response (MLR), a useful tool in the assessment of low-frequency auditory sensitivity, can be consistently recorded in young children during wakefulness, stages 1 and 2, and REM sleep. Responses are often absent or questionable during stage 4. An on-line measure indicating favorable periods for recording MLR during sleep is important for interpretation of absent potentials. Here, for children 5 to 7 years old, the reliability and detectability of MLR was compared to sleep state and the dominance of delta activity (0-3 Hz) in the EEG frequency spectrum. Dominance of delta activity, a characteristic of stage 4, was expressed in a "delta ratio," a measure of relative EEG energy in the 0 to 3 Hz frequency spectrum. A fixed delta ratio (DR = 9) allowed the differentiation of periods favorable for MLR. MLR wave Pa amplitude and latency also varied with delta ratio. Results indicate that on-line monitoring of the delta ratio will allow reliable testing of MLR in clinical situations. PMID- 8472882 TI - A comparison of auditory brain stem response thresholds and latencies elicited by air- and bone-conducted stimuli. AB - Auditory brain stem responses (ABRs) were measured for stimuli presented both by air conduction and by bone conduction. Stimuli included clicks and tone bursts at octave frequencies from 250 to 4000 Hz. ABR thresholds were comparable for air- and bone-conducted stimuli. Wave V latencies were longer for bone-conducted stimuli compared to similar responses for air conduction. This effect was evident for both clicks and tone bursts. The fact that these latency differences were largely independent of stimulus spectrum suggests that they are not due to differences between the frequency responses of air and bone conduction transducers. This finding is expected when one considers the interaction between output, threshold, and frequency for both transducer types. These data also suggest that there are inherent differences in transmission by air and bone conduction that affect response latency but are unrelated to the amplitude spectrum in the signal. PMID- 8472883 TI - The effect of forward masker duration, rise/fall time, and integrated pressure on auditory brain stem evoked responses in human newborns and adults. AB - The effects of duration, rise/fall time, integrated pressure, and intensity of a forward masker on the auditory brain stem evoked response (ABR) were examined in three studies. Keeping peak masker intensity constant, integrated masker pressure was a better predictor of ABR latency prolongation than masker duration or rise/fall time in human newborns. Masker effects varied as a function of masker intensity. Greater ABR latency prolongation was observed for more intense maskers. Furthermore, latency prolongation was observed with increasing masker duration for high-intensity, but not low-intensity maskers. Forward masking had a greater effect on newborn wave V latencies than adult wave V latencies; however, increasing masker duration had similar effects on newborn and adult wave V latencies. PMID- 8472884 TI - 1,25-Dihydroxy vitamin D3 stimulation of TGF-beta expression in chick embryonic calvarial bone. AB - Bone is a highly active producer of the cytokine, transforming growth factor-beta (TGF-beta), which is likely to be functionally involved in the regulation and maintenance of bone development and growth. In addition, bone functions are also regulated by the major calciotropic hormone, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). This investigation aims to examine the possible relationship between TGF-beta and 1,25(OH)2D3 using an unique calcium-deficient chick embryonic model. By means of long-term culture without the eggshell (shell-less or SL culture), chick embryos may be rendered severely calcium-deficient with gross undermineralization of the skeleton. We have previously observed that the calvaria of these SL embryos develop abnormal chondrogenic phenotype, with production of collagen type II, and elevated TGF-beta expression. Administration of 1,25(OH)2D3 to the SL embryos in vivo on incubation days 10 and 12 (SL + D embryos) resulted in near-normal serum calcium on day 14 and improved calvarial calcification. However, TGF-beta expression in the SL + D calvaria was further increased compared to untreated SL calvaria, when analyzed at both the mRNA and protein levels. Histolocalization of gene expression by immunohistochemistry and in situ hybridization revealed that cells in the less mineralized orbital and temporal zones of the calvarium are particularly affected by the 1,25(OH)2D3 treatment. Interestingly, the increased TGF-beta expression resulting from 1,25(OH)2D3 treatment did not correct the aberrant collagen phenotype in the SL calvaria. These observations suggest that TGF-beta expression by bone cells in situ is stimulated by 1,25(OH)2D3, and that normal cellular differentiation and morphogenesis of the embryonic calvaria are dependent on proper and balanced TGF beta expression as well as the state of tissue mineralization. PMID- 8472885 TI - Pathology of 46,XY pure gonadal dysgenesis: absence of testis differentiation associated with mutations in the testis-determining factor. AB - Individuals with 46, XY pure gonadal dysgenesis present with a completely female phenotype. These individuals develop bilateral streak gonads and have normal Mullerian structures. The apparent absence of testicular tissue in these individuals suggests a mutation in the initial steps of the male sex-determining pathway. A candidate gene for the primary signal in this pathway was recently cloned (SRY) which encodes a protein with a DNA-binding capacity. In a study of 14 XY females with pure gonadal dysgenesis harbouring SRY, we analysed the histology of the gonads and compared it to the presence or absence of mutations in the SRY open reading frame (SRY-orf). The histological analysis revealed two distinct groups of streak gonads. In the first group, the gonad was composed of exclusively ovarian-like stroma, with sclero-hyaline nodules in some areas. No tubules were observed. The gonads in the second group were composed of undifferentiated stroma harbouring either tubules or a rete structure. This suggests that in the latter group some differentiation (towards testis formation) has occurred, whereas in the first group ovarian differentiation has been interrupted. Individuals with mutations in the SRY-orf were found to have streak gonads of the first group, whereas most of the remaining XY females without detectable mutation in the SRY-orf had streak gonads belonging to the second group. On the basis of histology, it may be possible to distinguish between mutations in the sex-determining or sex-differentiation pathways. We suggest that SRY may play a role in rete testis formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472886 TI - Endogenous activation of c-myc expression and DNA synthesis in serum-starved neonatal rat smooth muscle cells. AB - Earlier studies have shown that smooth muscle cells (SMC) from arteries of neonatal and adult rats differ markedly in their in vitro growth characteristics. Since some of these differences may be relevant to the proliferation of SMC in atherosclerotic plaques we examined the expression of three proto-oncogenes (c fos, c-jun, and c-myc) and an SMC-specific differentiation marker (alpha-actin) in cultured SMC. In presence of serum cultured adult SMC contained lower levels of alpha-actin mRNA than neonatal cells. In neonatal cells serum-starvation resulted in a distinct increase in both c-myc and alpha-actin mRNA levels, whereas the expression of these genes appeared to be unaffected in adult cells. Transfer of adult SMC proliferating in the presence of fetal calf serum to serum free medium for 48 h almost completely inhibited DNA synthesis, whereas transfer of neonatal SMC to serum-free medium reduced DNA synthesis only to about 50%. Serum-starved adult and neonatal SMC did not contain c-fos or c-jun transcripts, but in both cell types serum-stimulation resulted in a comparable increase in the expression of both genes. The present results demonstrate clear differences in the mechanisms regulating gene expression in adult and neonatal SMC. PMID- 8472888 TI - Nutrients and the human genome: new frontiers for the next century. PMID- 8472887 TI - Murine erythroleukemia cells contain two distinct GATA-binding proteins that have different patterns of expression during cellular differentiation. AB - GATA-1 is a major transcription factor of the erythroid lineage that has been implicated in the induced expression of a variety of red cell-specific genes during terminal differentiation of murine erythroleukemia cells. Although the GATA-1 protein is present at nearly equal levels before and after differentiation of murine erythroleukemia cells, in this study it was found that in the early commitment stages of the differentiation program there is a transient decrease in the GATA-1 mRNA and DNA binding activity levels due to a temporary block in transcription of the gene. Moreover, using a whole cell extraction procedure it was discovered that murine erythroleukemia cells contain a second GATA binding activity (denoted GATA-rel) which appears to be distinct from the GATA-1 factor based on its non-reactivity to two GATA-1 antisera. This protein has a limited tissue specificity, as it could not be detected in extracts from CHO, NIH 3T3, or COS cells. Similarly to the GATA-1 DNA-binding activity, the GATA-rel activity decreased during the early stages of differentiation. However, unlike GATA-1, GATA-rel activity did not return to pre-induced levels at later times. These results suggest that changes in gene expression during erythroid terminal differentiation may involve an interplay on levels of different GATA-binding factors. PMID- 8472889 TI - Dr. Kinyoun's legacy: the international dimensions of the National Institutes of Health. PMID- 8472890 TI - Thromboregulation: multicellular modulation of platelet reactivity in hemostasis and thrombosis. AB - Blood platelets represent the first line of host defense when normal vessels are injured. Platelet adhesion to subendothelium, aggregation, and further platelet recruitment culminate in hemostatic plug formation, which is accompanied by the consolidating effect of fibrin deposition on and between platelets. The process is multicellular in that erythrocytes promote and neutrophils inhibit platelet plug formation. Endothelial cells in proximity possess three protective mechanisms (thrombo-regulators) for limiting the size of the hemostatic plug ADPase, eicosanoids, endothelium-dependent relaxing factor/NO. We propose that in advanced atherosclerotic blood vessels such as coronary arteries, an ulcer or fissure in the fibrous cap of the atheroma serves as an agonist that transforms the platelet into a major prothrombotic offender. Induction of excessive platelet activation overcomes the normal thromboregulatory mechanisms. Erythrocytes further activate platelets, even in the presence of aspirin, and neutrophil blockage of platelet reactivity is insufficient to prevent impending vascular occlusion. Appreciating that multiple cell types and metabolic pathways are involved in modulation of platelet reactivity in vascular occlusion is a relatively recent concept. Strategies designed to restore processes such as thromboregulation may serve to improve therapeusis in thrombosis, which at present is far from optimal. PMID- 8472891 TI - Endothelial cell gene expression in response to injury. AB - Endothelial cells respond to injury with acute alterations in mediator generation and surface molecule expression. Endothelial cells may respond, depending on the stimulus, by altering the expression of various genes whose products are central to endothelial cell matrix remodeling, coagulation, and fibrinolysis, as well as interactions with polymorphonuclear leukocytes, platelets, and lymphocytes and in angiogenesis. These responses comprise endothelial activation or differentiation. The molecular events involved in endothelial perception of injury and in regulation of gene expression by cytokines, reactive oxygen intermediates, and mechanical forces are discussed. In addition, because endothelial cells from different sites exhibit heterogeneity regarding their injury responses, where possible this heterogeneity in endothelial gene expression is highlighted. PMID- 8472892 TI - Glycoprotein biosynthesis in yeast. AB - Many proteins in the yeast Saccharomyces cerevisiae are modified by the attachment of N-linked saccharides to asparagine, of O-linked mannose glycans to serine or threonine, and of glycosylphosphoinositol membrane anchors. The biosynthetic events leading to these modifications are coupled to the secretory pathway. Early stages of N-linked glycosylation and the formation of glycosylphosphoinositol anchors have been conserved through evolution of eukaryotes. Studies of yeast offer a variety of genetic and molecular biological approaches, which have led to the isolation of different glycosylation mutants and of genes for enzymes involved in glycosylation. Yeast mutants are useful to identify biosynthetic intermediates, to establish whether a given enzyme is essential for viability, and to determine how cellular functions are affected when glycosylation is perturbed. Yeast glycosylation mutants and genes can be used to identify their counterparts in other eukaryotes. PMID- 8472893 TI - Choline phospholipids: signal transduction and carcinogenesis. AB - Phospholipids act as vital elements in transmembrane signaling. Agonist-induced hydrolysis of phosphatidylinositides has been established as a major mechanism for transmitting messages into the interior of cells via protein phosphorylation cascades, ultimately regulating gene transcription. There is a growing body of evidence that choline phospholipids (phosphatidylcholine, sphingomyelin, and their metabolites) also are important mediators and modulators of transmembrane signaling. These functions may explain how choline phospholipids influence normal physiological processes as well as a diverse group of pathological processes. PMID- 8472894 TI - Aspects of life development at deep sea hydrothermal vents. AB - Hydrothermal vent organisms are living in an unexpected deep-sea environment, several thousand meters below the surface, where the earth's crustal plates are spreading apart. The vent fluids are usually hot (350 degrees C), anoxic, and contain high concentrations of hydrogen sulfide. This environment may be considered as extreme given the pressure, the high temperature, the chemical toxicity of the fluids, and the total lack of photosynthetic production for animal nutrition. The recent discovery of the unique fauna of the hydrothermal vent communities has brought an unexpected mode of animal nutrition in which chemoautotrophic bacterial symbionts are maintained within specialized cells of the host animal. The bacterial symbionts obtain energy by oxidizing reduced sulfur compounds from the environment. A portion of this fixed carbon is used by the eukaryotic host. The present review will focus on four of the main topics studied on the paradigmatic vent organism Riftia pachyptila, a giant gutless tube worm: 1) the chemoautotrophic symbiosis, 2) the toxicity of hydrogen sulfide, 3) the characteristics of the extracellular matrices of the worms, especially data obtained on collagens, and 4) the influence of temperature and pressure on worm biology. PMID- 8472895 TI - Proline-mediated enhancement of hepatocyte function in a collagen gel sandwich culture configuration. AB - Isolated rat primary hepatocytes were cultured between two layers of gelled collagen in a sandwich configuration that reinstates the cellular polarity necessary for long-term function in vitro. Maintenance of hepatocyte function, as measured by the secretion of albumin, was shown to be dependent on both the sandwich gel configuration and the continued presence of L-proline in the culture media. Cis-hydroxyproline, an analog of proline known to prevent the proper folding of triple helical collagen molecules, inhibited the response of sandwiched hepatocytes to proline in a dose-dependent and reversible manner. The addition of cis-hydroxyproline to cultures established for 7 days also resulted in the inhibition of hepatocyte function. These data support the hypothesis that continued collagen synthesis by hepatocytes is critical for hepatocyte function in the sandwich gel configuration. PMID- 8472897 TI - Brain metabolism, "ferrin," and non-carbohydrate oxidation. PMID- 8472896 TI - Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. AB - Mononuclear leukocytes preferentially accumulate in the central nervous system (CNS) during the course of experimental autoimmune encephalomyelitis (EAE). To address factors that govern leukocyte trafficking in EAE, we monitored expression of mRNAs encoding IP-10 and JE/MCP-1, which are members of a family of chemoattractant cytokines. A transient burst of IP-10 and JE/MCP-1 mRNA accumulation in the CNS occurred, in close relation to the onset of histologic and clinical disease. In situ hybridizations showed, unexpectedly, that astrocytes were the major source of mRNAs encoding IP-10 and JE/MCP-1. These observations implicate astrocyte-derived cytokines as potential chemoattractants for inflammatory cells during EAE. PMID- 8472899 TI - Decolorization of industrial effluents containing reactive dyes by actinomycetes. AB - Actinomycete strains have been identified which decolorize effluents containing different types of reactive dyes. Adsorption of anthraquinone, phthalocyanine and azo dyes to the cells of some of the strains resulted in the decolorization of the effluents, but no degradation of the dyes was observed. In contrast, effluents containing an azo-copper complex and a formazan-copper complex dye were almost completely decolorized by several of the strains without adsorption to the cells. The observed changes in the visible spectra indicated a degradation during incubation with the strains. PMID- 8472898 TI - A natural isolate of Pseudomonas maltophila which degrades aromatic sulfonic acids. AB - A natural isolate, designated BSA56, which was originally selected for growth with benzene sulfonic acid as sole carbon and energy source, was identified as a strain of Pseudomonas maltophila. Strain BSA56 grew on a wide range of aromatic sulfonic acids and was shown to release sulfite from benzene sulfonic acid and 2 naphthalene sulfonic acid. Although it also grew on toluene sulfonic acid and pyridine sulfonic acid, no significant sulfite release was observed with these substrates. Release of sulfite from benzene sulfonic acid was greatly promoted by the presence of glycerol. The ability to release sulfite was induced by growth in the presence of benzene sulfonic acid and was repressed almost entirely by substrates allowing rapid growth such as acetate. Strain BSA56 grew better at 30 degrees C than 37 degrees C on most aromatic substrates, but the reverse was true for most aromatic sulfonates. Several mutants of BSA56 were isolated with defects in benzoate, salicylate, or gentisate metabolism. However, all these mutants retained the ability to degrade the aromatic sulfonates. PMID- 8472900 TI - EnvC, a new lipoprotein of the cytoplasmic membrane of Escherichia coli. AB - A gene product with an apparent molecular mass of approximately 39,000 Da can be identified in the cytoplasmic membrane of Escherichia coli upon expression of cloned envC. In this communication we report that the product was labelled with [3H]glycerol and [3H]palmitic acid, and a precursor molecule of increased molecular mass was accumulated when cells were treated with globomycin, a specific inhibitor for the prolipoprotein signal peptidase. The same precursor molecule was encoded by an envC mutant gene, in which the cysteine residue in a pentapeptide sequence, Leu-Ile-Ala-Gly-Cys24 within the amino terminal region of EnvC, was replaced by tryptophane (Trp24). This protein was not labelled with [3H]glycerol. The results demonstrate that the envC gene product represents a new lipoprotein of the cytoplasmic membrane of E. coli. PMID- 8472901 TI - Analysis of common antigen of flagella in Bacillus cereus and Bacillus thuringiensis. AB - Flagellar antigen of Bacillus cereus H.1 was purified and tested for serodiagnostic antigen by ELISA. The antibody against the flagellar antigen of B. cereus H.1 reacted not only with the homologous specific antigen but also reacted with the flagellar antigens of 23 strains of B. cereus. This common flagellar antigen of B. cereus was found to be due to 61-kDa protein by SDS-PAGE and immunoblot assay. Monoclonal antibody H15A5 against common antigenic epitope of B. cereus also reacted with flagellar antigens of 21 strains of Bacillus thuringiensis by ELISA. This monoclonal antibody reacted with the 61-kDa protein of the flagella of B. cereus H.1 and H.2 and B. thuringiensis Kurstaki HD1, Alesti and Aizawai juroi by immunoblot analysis. These results indicated that the common antigenic epitope of the 61-kDa protein existed in the flagella both of B. cereus and B. thuringiensis. PMID- 8472902 TI - A NheI macrorestriction map of the Neisseria meningitidis B1940 genome. AB - A macrorestriction map of the Neisseria meningitidis strain B1940 genome was constructed by two-dimensional pulsed-field gel electrophoresis (2D-PFGE) techniques. Digestion of the genomic DNA with the restriction endonuclease NheI revealed 15 fragments between 10 kb and 450 kb. The sum of the fragments and resolution of the linearized chromosome yielded a total genome size of about 2.3 Mbp. By overlapping methylation with the AluI-methylase six NheI recognition sites could be blocked. Fragments were ordered by partial/complete 2D-PFGE of genomic DNA with and without prior AluI methylation, respectively. All nine AluI methylase/NheI and 14 NheI restriction sites could be mapped on a single circular chromosome. This map will serve as a useful tool for further genetic analysis of meningococci and exemplifies the power of non-radioactive 2D-PFGE techniques to construct large physical genome maps with a single restriction enzyme. PMID- 8472903 TI - Mice are protected against Bordetella pertussis infection by intra-nasal immunization with filamentous haemagglutinin. AB - Intra-nasal immunization of mice with purified Bordetella pertussis filamentous haemagglutinin (FHA) or a crude cell sonicate was shown to protect against subsequent B. pertussis aerosol challenge. Immunization with FHA was found to be the most effective and resulted in complete clearance of the bacterial infection from the lungs within 14 days. Serum IgG and lung IgA anti-FHA antibodies were detectable within 4 weeks of the first immunization and anamnestic responses were seen following secondary immunization and subsequent challenge with B. pertussis. Nasal administration of pertussis antigens is a route which induces good systemic serum, as well as local secretory, antibody responses. PMID- 8472904 TI - Comparison of outer membrane protein profiles of Vibrio vulnificus biotypes 1 and 2. AB - The outer membrane proteins of 17 Vibrio vulnificus biotype 2 strains from Japanese and European eels, and 12 biotype 1 strains from clinical and environmental sources have been compared. The overall profile in both biotypes was similar, and a major protein band of molecular mass 36 kDa was detected in the majority of the strains. Differences in the minor bands allowed differentiation of strains from different origins, suggesting that outer membrane protein profiles could be useful as epidemiological markers in the species V. vulnificus. Immunoblotting with antisera to whole cells of selected strains of biotypes 1 and 2 showed a strong antigenic response to outer membrane proteins 66, 60, 48, 46 and 44 kDa; these were common to all strains examined, independent of their biotypes and origins. These results demonstrate the presence of antigenically related outer membrane proteins in both biotypes of V. vulnificus. PMID- 8472905 TI - Surface films of Escherichia coli colonies. AB - Escherichia coli colony surfaces were examined using SEM and TEM. The results indicated that bacterial colonies in the course of their development produce surface films which become thicker with increased growth duration. Membrane vesicles contribute to the formation of the surface film. The complex organization of the film suggests that it may perform specific functions. PMID- 8472906 TI - The fdp1 and cif1 mutations are caused by different single nucleotide changes in the yeast CIF1 gene. AB - The allelism between the mutations cif1 and fdp1 from Saccharomyces cerevisiae has been demonstrated using PCR techniques and complementation of function. The cif1 mutation results in a shortened version of the protein while the fdp1 mutation introduces a charged residue in a highly hydrophobic stretch. PMID- 8472907 TI - Accumulation and intracellular compartmentation of lithium ions in Saccharomyces cerevisiae. AB - Accumulation of Li+ in Saccharomyces cerevisiae X2180-1B occurred via an apparent stoichiometric relationship of 1:1 (K+/Li+) when S. cerevisiae was incubated in the presence of 5 and 10 mM LiCl for 3 h. Other cellular cations (Mg2+, Ca2+ and Na+) did not vary on Li+ accumulation, although lithium chemistry dictates a degree of similarity to Group I and II metal cations. Compartmentation of Li+ was mainly in the vacuole which accounted for 85% of the Li+ accumulated after a 6-h incubation period. The remainder was located in the cytosol with negligible amounts being bound to cell fragments including the cell wall. Transmission electron microscopy of Li(+)-loaded cells revealed enlarged vacuoles compared with control cells. This asymmetric cellular distribution may therefore enhance tolerance of S. cerevisiae to Li+ and ensure that essential metabolic processes in the cytosol are not disrupted. PMID- 8472908 TI - Differential effects of anticytoskeletal compounds on the localization and chemical patterns of actin in germinating conidia of Neurospora crassa. AB - Anti-actin drugs, cytochalasins A and B, inhibited both normal single, and benomyl-induced multiple, germ tube outgrowth from conidia of Neurospora crassa. Actin was cytochemically found to be concentrated in each of the benomyl-induced germ tube tips. No significant quantitative changes either in total actin or its isoforms were measured in the inhibitor-treated germlings. While intact microtubules are required for normal, monopolar axiation of the germ tube, they appear not to be necessary for benomyl-induced multipolar outgrowth which, in contrast, still requires intact actin microfilaments. Microfilaments and microtubules thus play complementary roles in the normal germination of conidia. PMID- 8472909 TI - A truncated glucoamylase gene fusion for heterologous protein secretion from Aspergillus niger. AB - The secreted yield of hen egg-white lysozyme (HEWL) from the filamentous fungus Aspergillus niger was increased 10-20-fold by constructing a novel gene fusion. The cDNA sequence encoding mature HEWL was fused in frame to part of the native A. niger gene encoding glucoamylase (glaA), separated by a proteolytic cleavage site for in vivo processing. Using this construct, peak secreted HEWL yields of 1 g/l were obtained in A. niger shake flask cultures compared to about 50 mg/l when using an expression cassette lacking any glaA coding sequence. The portion of glaA used in the gene fusion encoded the first 498 amino acids of glucoamylase (G498) and comprised its secretion signal, the catalytic domain and most of the O glycosylated linker region which, in the entire glucoamylase molecule, spatially separates and links the catalytic and starch-binding domains. PMID- 8472910 TI - Cloning and expression of the D-ribulose-1,5-bisphosphate carboxylase/oxygenase form II gene from Thiobacillus intermedius in Escherichia coli. AB - Both form I and II ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) genes were detected in Thiobacillus intermedius by heterologous hybridization using specific probes from Anacystis nidulans and Rhodobacter sphaeroides, respectively. However, only the previously reported form I enzyme could be demonstrated in cells grown under a number of different conditions. The reason(s) why the form II gene is not expressed in T. intermedius is/are not clear at this time. The form II gene was isolated from a lambda library by screening with the Rb. sphaeroides probe. A SalI fragment from this clone was ligated into pUC8 and transformed into Escherichia coli DH5 alpha. Subclones pTi20IIA and pTi20IIB representing both orientations relative to the lac promoter were isolated. Low levels of RuBisCO activity were detected in both induced and non-induced pTi20IIA indicating the probable expression from a T. intermedius promoter. Induced pTi20IIB produced much higher levels of enzyme activity. Analysis of cell-free extracts using sucrose density gradients confirmed the expression of a form II RuBisCO similar in size to that found in Rhodobacter capsulatus. Other Calvin cycle genes were not clustered with either the form I or form II genes. PMID- 8472911 TI - Glucose-fructose oxidoreductase, a periplasmic enzyme of Zymomonas mobilis, is active in its precursor form. AB - Glucose-fructose oxidoreductase (GFOR) is a periplasmic enzyme of the ethanologenic, Gram-negative bacterium Zymomonas mobilis. It contains tightly bound NADP+ as cofactor. In Z. mobilis GFOR-recombinant strains, a precursor form of GFOR was accumulated. To assay the preGFOR for its NADP(H) content and enzymatic activity, it was purified from an overproducing strain. Using SDS-PAGE, the precursor subunit size was determined to approximately 45 kDa (compared with a 40 kDa subunit size for the mature GFOR subunit). The N-terminal amino acid sequence of the precursor was determined. The N-terminal residues of the GFOR matched with the signal sequence from the DNA sequence of the gene gfo. The precursor form of GFOR was enzymatically active and contained the cofactor NADP(H). PMID- 8472912 TI - Using fusions with luxAB from Vibrio harveyi MAV to quantify induction and catabolite repression of the xyl operon in Staphylococcus carnosus TM300. AB - The luxA,B genes from the Gram-negative marine bacterium Vibrio harveyi MAV were used in Staphylococcus carnosus TM300 as a reporter system for regulated expression of xylose utilization. The luciferase genes were fused to the xyl operon from Staphylococcus xylosus C2a. Expression of bioluminescence was induced through addition of xylose and repressed in the presence of glucose. A method to quantitate bioluminescence directly from the culture is described. PMID- 8472913 TI - Artificial neural network analysis of pyrolysis mass spectrometric data in the identification of Streptomyces strains. AB - Sixteen representatives of three morphologically distinct groups of streptomycetes were recovered from soil using selective isolation procedures. Duplicated batches of the test strains were examined by Curie-point pyrolysis mass spectrometry and the first data set used for conventional multivariate statistical analyses and as a training set for an artificial neural network. The second set of data was used for 'operational fingerprinting' and for testing the artificial neural network. All of the test strains were correctly identified using the artificial neural network whereas only fifteen of the sixteen strains were assigned to the correct group using the conventional operational fingerprinting procedure. Artificial neural network analysis of pyrolysis mass spectrometric data provides a rapid, cost-effective and reproducible way of identifying and typing large numbers of microorganisms. PMID- 8472914 TI - A stereospecific alignment between the promoter and the cis-acting sequence is required for Lrp-dependent activation of ilvIH transcription in Escherichia coli. AB - The leucine-responsive regulatory protein (Lrp) is a DNA binding protein that affects, either positively or negatively, the expression of several E. coli genes. The ilvIH operon is positively regulated by Lrp and leucine counteracts this effect reducing 5- to 10-fold the efficiency of ilvIH transcription. An investigation of the mechanism of transcription activation of the ilvIH operon by Lrp indicated that: (i) a stereospecific alignment between the ilvIH promoter and the cis-acting sequence upstream of it is required for activation; (ii) a correct distance between the promoter and the adjacent cis-acting sequence is needed for leucine to counteract the positive role of Lrp; (iii) Lrp fails to activate transcription when the cis-acting region is placed several hundred base pairs upstream of the ilvIH promoter. PMID- 8472915 TI - Oligomers of 4-chloroaniline are intermediates formed during its biodegradation by Phanerochaete chrysosporium. AB - Lignin peroxidase H2 (LP-H2) from Phanerochaete chrysosporium oxidized 4 chloroaniline to form several oligomers. Included among the compounds identified were: 4,4'-dichloroazobenzene, 2-(4-chloroanilino)-5-hydroxybenzoquinone-di-4 chloroanil and 2-amino-5-(4-chloroanilino) benzoquinone-di-4-chloroanil. In contrast to results by others, we showed that oligomers of 4-chloroaniline were also formed by the fungus in vivo. It was also demonstrated that, although these potentially toxic intermediates are made, they are also degraded. PMID- 8472916 TI - A monoclonal antibody to Shigella dysenteriae serotype 13 cross-reacting with Shiga toxin. AB - A monoclonal antibody (mAb ICT6) was produced against the newly described Shigella dysenteriae serotype type 13. The mAb was of IgM isotype and recognized purified Shiga toxin in ELISA and immunoblot. It also recognized periplasmic extract S. dysenteriae type 13 in immunoblot as did an affinity-purified polyclonal rabbit antiserum and a previously described monoclonal antibody to the B subunit of Shiga toxin. The mAb ICT6 did not neutralize the cytotoxic effects or S. dysenteriae type 13, Shiga toxin or periplasmic extracts of S. dysenteriae type 1 for HeLa cells. PMID- 8472917 TI - Phenylacetate-coenzyme A ligase is induced during growth on phenylacetic acid in different bacteria of several genera. AB - Nine different bacterial strains that utilise phenylacetic acid as the only carbon and energy source were isolated from samples of different geographical origin. The isolates were characterised taxonomically and physiologically. Evidence is presented that in all the isolates as well as in four previously isolated control strains with the ability to utilize phenylacetic acid, the enzyme phenylacetate-CoA ligase is specifically induced during growth on phenylacetic acid. The Michaelis constant (Km) in one Pseudomonas strain was sufficiently low (-1 mM) to suggest that the enzyme may have a role in phenylacetic acid metabolism. PMID- 8472918 TI - Escherichia coli K-12 ferrous iron uptake mutants are impaired in their ability to colonize the mouse intestine. AB - The streptomycin-treated mouse colonization model was used to investigate the role of the Fe2+ uptake system (Feo) of Escherichia coli K12 in the colonization of the mouse intestine. Mutants impaired in the uptake of Fe2+ ions were shown to be deficient also in their colonization ability. Both enterochelin-producing and enterochelin-nonproducing Escherichia coli feo mutants were unable to colonize the mouse intestine. These results demonstrated that Fe(II) is an essential source of iron for E. coli grown in the intestine. PMID- 8472919 TI - A PCR primer-specific to Cylindrocarpon heteronema for detection of the pathogen in apple wood. AB - An oligonucleotide primer (ChInt) was synthesised from the variable internally transcribed spacer (ITS) 1 region of ribosomal DNA (rDNA) of Cylindrocarpon heteronema. PCR with primers ChInt and ITS4 (from a conserved sequence of the rDNA) amplified a 470-bp fragment from several isolates of C. heteronema but not from various apple wood saprophytes. Amplification of this fragment was achieved from 1-2 pg of fungal DNA. These primers amplified a fragment of the same size from DNA extracted from cankered wood but only after impurities were removed from the DNA on a Qiagen tip-5 column. Southern hybridization analysis confirmed the 470-bp fragment from C. heteronema DNA and cankered wood to be identical. PMID- 8472920 TI - Androgen binding proteins in Cochliobolus lunatus. AB - Testosterone and 4-androstene-3,17-dione (androstenedione) binding proteins were found in the cytosol of Cochliobolus lunatus, a filamentous fungus. The maximal androgen binding occurred by 120 min at 0 degrees C. Androgen binding proteins were degraded by protease treatment and at high temperature. The mean Kd determined for testosterone binding protein (TBP) by Scatchard analysis was 4.5 nM and the maximum capacity Bmax was 120 fmol/mg protein; for androstenedione binding protein (ABP) the Kd was 8 nM and Bmax was 390 fmol/mg protein. Steroid binding specificity for TBP, in order of decreasing affinity, was the following: androstenedione, progesterone, dihydrotestosterone, 17 beta-estradiol and estrone. The same order was found for ABP. PMID- 8472921 TI - Acetoin production in Saccharomyces cerevisiae wine yeasts. AB - One hundred strains of Saccharomyces cerevisiae were examined for the capacity to produce acetoin in synthetic medium and in grape must. The low production of acetoin was found to be the more common pattern in this species. Most strains exhibited a similar distribution in both media, production ranging from non detectable amounts to 12 mg l-1. Only four strains produced high quantities of acetoin, up to 29.5 mg l-1 in synthetic medium and up to 194.6 mg l-1 in grape must. This biometric study showed the existence of two phenotypes, "low and high acetoin production", that could be selected for conferring a desirable flavour of the final product. PMID- 8472922 TI - Identification of sialic acids on the cell surface of hyphae and yeast forms of the human pathogen Paracoccidioides brasiliensis. AB - Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis, when grown in a synthetic medium, expresses at the cell surface of both yeast and mycelial forms acidic glycoconjugates containing N-acetylneuraminic acid units. Sialic acids were extracted using mild hydrolytic conditions, and were identified by thin-layer and gas chromatography, standard colorimetry, reaction with periodate resorcinol and mass spectrometry. Their surface location was inferred from fluorescent-lectin (Limulus polyphemus agglutinin) binding to whole cells abrogated by previous treatment with neuraminidase. Expression of sialic acids on virulent yeast forms of P. brasiliensis (3.7 x 10(6) residues per cell) may inhibit fungal phagocytosis during early infection, when the immunological response is still being built up. PMID- 8472923 TI - Phosphate-starvation induced changes in Thiobacillus ferrooxidans. AB - We have analysed the response of the acidophilic chemolithotroph Thiobacillus ferrooxidans to phosphate starvation. Cultivation of the bacteria in the absence of added phosphate induced a remarkable filamentation of the cells. Polyacrylamide gel electrophoresis revealed several proteins whose levels increased upon phosphate limitation, as well as some polypeptides that were exclusively synthesized under this growth limitation. One of the proteins whose level increased by the lack of phosphate was apparently an acid phosphatase with a pH optimum of about 3.8, and a molecular mass of 26 kDa, which was located in the periplasm. The N-terminal sequence of a 26 kDa protein derepressed by starvation, which may correspond to the T. ferrooxidans starvation, which may correspond to the T. ferrooxidans phosphatase, showed 30% and 35% identity with the known sequence of Lysobacter enzymogenes and Escherichia coli alkaline phosphatases, respectively. PMID- 8472924 TI - Arginine utilization by Mycoplasma fermentans is not regulated by glucose metabolism: a 13C-NMR study. AB - 13C-NMR studies on the effect of glucose metabolism on arginine hydrolysis in Mycoplasma fermentans cells have been performed using a continuous perfusion technique. With this procedure we were able to show, in the presence of glucose, the rapid accumulation of lactic acid and, in the presence of arginine, the formation of citrulline that is apparently further metabolized. As the accumulation of lactate and the breakdown of arginine were observed in the simultaneous presence of both substrates, it is suggested that the glucose utilization has little or no effect on the deimination of arginine to citrulline. PMID- 8472925 TI - Hydrostatic pressure is like high temperature and oxidative stress in the damage it causes to yeast. AB - A comparison of barotolerance, thermotolerance and oxygen tolerance was made under different physiological conditions, such as heat shocked and recovered state, different growth phases and changes of physiological conditions by mutations. The three kinds of tolerance showed similar features under different physiological conditions. We suggest that the damage caused by hydrostatic pressure may be essentially the same as that due to high temperature and oxidative stress in yeast. PMID- 8472926 TI - Glucose and zinc concentration influence fusarin C synthesis, ethanol synthesis and lipid composition in Fusarium moniliforme submerged cultures. AB - A fusarin C-producing Fusarium moniliforme strain was grown in submerged culture with defined media containing differing amounts of glucose (30 g/l or 90 g/l) and zinc (5 ppb or 3200 ppb). The influence of zinc on fusarin C synthesis and lipid composition was dependent on the initial glucose concentration. In cultures supplied with 30 g/l glucose, zinc inhibited fusarin C and lipid synthesis by diverting common substrates to ethanol synthesis. Zinc-supplemented cultures with 90 g/l glucose had ample carbon substrate to produce both ethanol and fusarin C. More total lipid with a higher unsaturated fatty acid content (more oleic acid and less stearic acid) was found in F. moniliforme biomass produced in zinc deficient media. PMID- 8472927 TI - Carnitine acetyltransferase is absent from acuJ mutants of Aspergillus nidulans. AB - The acuJ mutant of Aspergillus nidulans has been shown to lack carnitine acetyltransferase (CAT) activity when grown under conditions where this activity is readily detectable in wild-type strains. Revertants selected for growth on acetate recover CAT activity and the ability to grow on long-chain fatty acids. When growing on carbon sources such as sucrose, cytosolic acetyl coenzyme A was generated by adenosine triphosphate (ATP):citrate lyase. PMID- 8472928 TI - Purification and characterization of three carboxylesterases from Enterobacteriaceae. AB - The carboxylesterases from Proteus vulgaris, Salmonella enterica and Citrobacter amalonaticus were purified 104-, 95- and 120-fold, respectively by chromatography. The enzymes had similar catalytic activities but differed considerably in their inactivation by heat, di-isopropyl fluorophosphate and Cd2+, Zn2+, Hg2+ and Cu2+. Quantitative neutralization of hydrolytic activity with specific immunoglobulins indicated that the three enzymes were antigenically distinct. PMID- 8472929 TI - Lytic action of cloned pneumococcal phage lysis genes in Streptococcus pneumoniae. AB - The genes hbl3, cpl1 and cpl7 coding for the pneumococcal phage lytic enzymes HBL3, CPL1 and CPL7, respectively, have been cloned into shuttle plasmids that can replicate in Streptococcus pneumoniae and Escherichia coli. All these genes were expressed in E. coli under the control of either the lytP promoter of the lytA gene, which codes for the major pneumococcal autolysin, or the promoter of the tetracycline-resistance gene (tetP). In contrast, cpl1 and cpl7 genes that code for lysozymes were expressed in pneumococcus only under the control of tetP, whereas the hbl3 gene that codes for an amidase can be expressed using either promoter. The phage lysozymes or amidase expressed in S. pneumoniae M31, a mutant deleted in the lytA gene coding for short chains, were placed under physiological control since these transformed bacteria grew as normal 'diplo' cells during the exponential phase and underwent autolysis only after long incubation at 37 degrees C. The lysis genes appear to be expressed constitutively in the transformed pneumococci, since sharply defined lysis of these cultures could be induced prematurely during the exponential phase of growth by addition of sodium deoxycholate. PMID- 8472930 TI - Genetic epidemiology of autosomal recessive spastic ataxia of Charlevoix-Saguenay in northeastern Quebec. AB - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a disorder that has an elevated frequency in Saguenay-Lac-St-Jean (SLSJ) and Charlevoix, two geographically isolated regions in the past of northeastern Quebec. The incidence at birth and the carrier rate in SLSJ were estimated at 1/1,932 liveborn infants and 1/22 inhabitants, respectively, for the period 1941-1985. The mean inbreeding coefficient was twice higher and the mean kinship coefficient 3 times higher among the ARSACS families than among control families. In the SLSJ region, the birth places of the ARSACS individuals and their parents did not show a clustered distribution. The genealogical reconstruction suggests that the high incidence of ARSACS in SLSJ and Charlevoix is likely to be the result of a founder effect. Because the disease is apparently unknown elsewhere in the world and a high proportion of French Canadians presently living in eastern Quebec have ancestors coming from Perche, a small region in France, it also suggests that a unique mutation accounts for most, if not all, of the ARSACS cases known in these regions. PMID- 8472931 TI - Apo E allele frequencies in younger (age 42-50) vs older (age 65-90) women. AB - Allelic variation at the apolipoprotein E (Apo E) structural locus has been shown to influence concentrations of total cholesterol and low density lipoprotein cholesterol (LDL-C). Apo E has six phenotypes resulting from three common alleles at this locus. The epsilon 2 allele is associated with lower LDL-C and the epsilon 4 allele with higher LDL-C. In the current study, we compared the epsilon allele distribution in two cohorts of white women recruited from population based listing of southwestern Pennsylvania. The "younger" cohort consisted of 473 women, age 42-50; the "older" cohort, 870 women, age 65-90. A comparison of the overall distribution of allele frequencies in the two cohorts was significantly different. The allele frequency of epsilon 4 was lower in the older cohort (0.098 vs. 0.122, P = 0.08) and the epsilon 2 allele frequency was higher (0.084 vs. 0.059, P = 0.05) in the older cohort. These observations are consistent with the hypothesis that there may be a selection against individuals with the epsilon 4 allele. However, future research is needed to confirm this observation and to compare survival in individuals by their epsilon allele. PMID- 8472932 TI - A form of sensorineural deafness is determined by a mitochondrial and an autosomal locus: evidence from pedigree segregation analysis. AB - We have previously reported a large Israeli-Arab pedigree with sensorineural deafness possibly determined simultaneously by two loci--one mitochondrial, and one autosomal recessive. This was analyzed by extending classic segregation analysis methods to the many nuclear families derived from the maternal line pedigree. Here we expand this pedigree and extend our analysis by using the regressive models for segregation analysis on the entire pedigree. The corresponding REGD computer program was utilized and the marrying-in males' and paternal line members' affection statuses were assigned as unknown to accommodate the exclusive maternal transmission pattern. For the autosomal locus, a simple autosomal recessive (q = 0.52) model with a nearly complete penetrance (0.93) was found to be the best-fitting model. Equally importantly, we were also able to use the power of the regressive models to test the hypothesis of mitochondrial heteroplasmy as an alternative for the proposed autosomal locus. We found no evidence for the heteroplasmy hypothesis as an explanation for the incomplete maternal transmission of deafness in this pedigree. Thus, even if the mitochondrial mutation occurred in a heteroplasmic distribution in the family members, this could not explain the familial aggregation in this pedigree, and an autosomal recessive locus is still required. These results provide further support for the concept that the sensorineural deafness occurring in this large Israeli-Arab pedigree results from simultaneous involvement of two genes at two different loci, one mitochondrial and likely homoplasmic, and the other autosomal and recessive. PMID- 8472933 TI - Cigarette smoking and trisomy 21 at amniocentesis. AB - Several studies raise the possibility that smoking during pregnancy is associated with a slightly decreased odds of trisomy 21 at birth. If it is, associations may reflect decreased incidence at conception, increased intrauterine loss (at one or several times in gestation), or both. Women (n = 13,729) undergoing prenatal diagnosis completed a questionnaire before learning karyotype results. For each women with a trisomy, up to 4 controls with chromosomally normal pregnancies, matched for age and hospital, were selected. Analyses drew on the 89 trisomy 21 control matched m-tuples in which diagnosis was by amniocentesis at 14-26 weeks. We compared the odds of smoking at last menstrual period and in the past in cases and controls. The odds of current smoking versus never smoking were decreased [adjusted odds ratio = 0.8, 95% confidence interval (CI) 0.4-1.6] and the odds of exsmoking increased (adjusted odds ratio = 1.4, 95% CI 0.9-2.4) in trisomy 21 cases. The association with current smoking was essentially unchanged when the unexposed reference group was defined as exsmokers and women who never smoked (adjusted odds ratio = 0.7, 95% CI 0.4-1.4). These results for current smoking agree well with a summary estimate based on combined studies of births. One interpretation is that at amniocentesis, as has been reported for births, current smoking is associated with a slightly decreased odds of trisomy 21. If associations at amniocentesis and birth are of equal magnitude, the explanation that observations at birth reflect increased loss in the second half of pregnancy with current smoking is unlikely to be correct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8472934 TI - Estimating age at onset distributions: the bias from prevalent cases and its impact on risk estimation. AB - Since many disorders have a variable age at onset, knowing the age at onset distribution of a disease facilitates epidemiologic analyses in several ways. The age at onset distribution is commonly used to estimate morbidity risks or the recurrence risks in genetic counseling. Unfortunately, estimation of a disease's age at onset distribution is not straightforward. The observed age at onset distribution obtained from prevalent cases is usually used in these epidemiologic analyses. Through simulation studies, we show that, in certain situations, the observed age at onset distribution has a non-negligible downward bias. This bias can lead to a substantial underestimation of the morbidity risk or the recurrence risk. The simulations also demonstrate that a non-parametric approach for correcting the age at onset distribution works well even when mortality increases after onset. The results have implications for diseases that have adult onset and/or increased mortality after onset. We suggest that researchers should use corrected age at onset distributions, rather than relying on observed distributions, in the calculation of either morbidity risks or recurrence risks. PMID- 8472935 TI - A generalized estimating equations approach to fitting major gene models in segregation analysis of continuous phenotypes. AB - This paper discusses the application of estimating equations methods based on a quadratic exponential model [Prentice and Zhao, 1991] as a potential competitor with full likelihood approaches to estimating the effect of major genes in a segregation analysis [Elston, 1981] of continuous phenotypes, in the single allele problem. We show that while the estimating equations methods based on the quadratic exponential family cannot be used by themselves to estimate all parameters of interest, an iterative two-stage approach can be used, in which the population allele frequency is first considered to be a known parameter, which permits the estimating equations method to estimate the remaining parameters. At the second stage a "pseudo-profile" loglikelihood based only on the founders is used to estimate the allele frequency. After each maximization of the pseudo profile loglikelihood at the second stage, the parameters in the first stage are reestimated using a new value of the allele frequency, and a new value of the second stage pseudo-profile loglikelihood is obtained. We used simulated pedigree data for illustrations. PMID- 8472936 TI - Distribution of the admixture test for the detection of linkage under heterogeneity. AB - The admixture test for the detection of linkage under heterogeneity is considered. We show that the null distribution of this test statistic has half its weight concentrated on zero and the other half on a complicated distribution that can be approximated by max (X1,X2) where X1 and X2 are independent X1(2) variables. We also investigate the stability of the size of the test for small samples. The power of this test to detect linkage, when heterogeneity is present, can be substantially greater than the standard test that assumes homogeneity. Even when heterogeneity is not present, the test is only slightly less powerful than the homogeneous test. This would suggest the use of the admixture test in preference to the homogeneous test if the presence of heterogeneity is at all suspected. PMID- 8472937 TI - Neuro-ophthalmology and psychiatry. AB - Neuro-ophthalmology and psychiatry interact over several issues. The neuro ophthalmologist can confirm the suspicion of nonorganic visual dysfunction by demonstrating the functional integrity of the visual system and the nonphysiologic nature of the visual complaints. He or she may recognize evidence of organic dysfunction in the patient with a presumed psychiatric diagnosis. In some cases, the pathology may be related to the use of certain psychiatric medications. Specialized examination techniques within the realm of neuro ophthalmology may provide subtle information about the functional integrity of the central nervous system in patients with psychiatric disease. Clinical and investigational collaboration between the neuro-ophthalmologist and the psychiatrist will provide the most appropriate patient management and may further our understanding of the biological basis of psychiatry. PMID- 8472938 TI - Etomidate anesthesia increases seizure duration during ECT. A retrospective study. AB - We reviewed charts of 28 consecutive depressed psychiatric inpatients who had received electroconvulsive therapy (ECT). As a preliminary investigation, we compared the effects of thiopental and etomidate anesthesia on seizure duration. Etomidate, a nonbarbiturate, has been shown to enhance seizure activity in other contexts. The mean age of our sample was 64 years. Because each patient received both etomidate and thiopental at various sessions during their course of ECT, each patient served as his or her own control. The mean proportion of etomidate sessions per patient was 54%. Mean seizure durations were significantly longer (p < 0.001) for the etomidate sessions as compared with the thiopental sessions. In contrast to some prior reports we found that the use of etomidate anesthesia in our sample of 28 consecutive inpatients enhanced seizure duration in ECT. Although controversial, some have advocated that longer seizure times will enhance effectiveness of ECT. We could not compare the anesthetic agents' clinical efficacy in relieving depression due to the retrospective nature of our study. PMID- 8472939 TI - Consultation-liaison psychiatry in Australia. AB - Consultation-liaison (C-L) psychiatry as a service entity has developed slowly and to a variable extent in Australia despite the presence of factors conducive to its development. These include a compulsory national health insurance system and a favorable disposition to the biopsychosocial model and to psychoanalytic ideas. C-L psychiatry, however, does enjoy a high profile in many undergraduate medical and postgraduate psychiatry teaching programs. Research on C-L psychiatry is emerging, complementing a strong history of research in psychosomatic medicine. An Australian and New Zealand C-L psychiatry interest group is being formed. Collaboration with the MICRO-CARES Consortium and the European Consultation-Liaison Workgroup is proving to be a great stimulus. PMID- 8472940 TI - Psychiatric morbidity in a pregnant population in Nigeria. AB - Psychiatric morbidity among 240 pregnant women attending an antenatal unit was assessed by a two-stage screening procedure, using the General Health Questionnaire (GHQ-30) and Present State Examination Schedule (PSE). The prevalence of psychiatric morbidity was found to be significantly associated with younger age (< 24 years), being primigravid, married for less than 1 year, having an unsupportive husband, and a previous history of induced abortion. It is suggested that more attention needs to be paid to the mental health of pregnant women in developing countries (where pregnancy rates and the risks associated with pregnancy/delivery are much higher than in the developed countries) at the primary, secondary, and tertiary levels of health care. PMID- 8472941 TI - Rapidly cycling bipolar II disorder following liver transplantation. AB - During the last decade the psychiatric aspects of liver transplantation have been widely described. Although affective complications are some of the most prevalent, a complete and persistent bipolar II syndrome following transplantation has never been reported before. In this paper we describe a patient who developed a rapidly cycling bipolar II disorder after liver transplantation. He presented a major depressive episode within the first 48 hours following transplantation, and subsequently started cycling from depression to hypomania with only brief periods of euthymia. One year after transplantation, only lithium carbonate has proved to be useful to ameliorate his persistent disorder. There was no premorbid or family history of affective illness. Although the course of the disorder seemed to be independent from any pharmacologic or psychosocial factor, it is suggested that transplantation, corticosteroids, and cyclosporine may have played some role in the pathogenesis of the syndrome. PMID- 8472942 TI - Screening for depression and anxiety in cancer patients using the Hospital Anxiety and Depression Scale. AB - Nine hundred and thirty inpatients and outpatients with cancer were approached to complete the Hospital Anxiety and Depression Scale (HADS). Eight hundred and nine (86.9%) of those approached participated in this screening. Using the suggested cutoff score of 8 for the anxiety and depression subscales, we found that 47.6% of this population would warrant further psychiatric evaluation. Twenty-three percent (23.1%) had scores 11 or greater and would be the most likely to have had anxiety (17.7%) or depressive (9.9%) disorders based on DSM-III-R criteria. Patients with active malignant disease and inpatient status were more likely to have higher depression scores. The HADS was an easily administered tool that identified a large proportion of cancer patients as having high levels of anxiety or depression. However, clinical psychiatric interviews were not performed, so it is not possible to determine what proportion of patients would benefit from treatment. PMID- 8472943 TI - Suicide evaluation in medical patients. A pilot study. AB - General hospital psychiatrists were given a pilot questionnaire aimed at characterizing patients evaluated for suicidality. Twenty-seven patients evaluated for suicidality in a 4-month period were studied for demographic, medical, psychiatric, and suicidal variables. Comparison with medical patients who had attempted/completed suicide in prior studies and recommendations to reduce suicidal impulses and improve the database were discussed. PMID- 8472944 TI - Recent life events, gender, and the control of diabetes mellitus. AB - Sixty-six outpatients with insulin-dependent diabetes mellitus (IDDM) filled in a life event questionnaire reflecting positive and negative life events perceived to have occurred over the past year. The difference in glycosylated hemoglobin (HbA1C) measures obtained before and after the 1-year period in question (Delta HbA1C) served as a proxy measure of change in metabolic control. Among males, those reporting predominantly negative life events showed poorer metabolic control than those reporting few negative life events or none. Among females, the greater the number of events reported, especially positive ones, the greater the change for the better in HbA1C over the event year studied. These results suggest that life events may be significant to metabolic control in insulin-dependent diabetes. This only becomes apparent, however, when the two genders are analyzed separately, as various relationships found in one sex may be lacking or even opposite to the other sex. The findings also suggest the importance to the diabetic of learning of life events both the relative lack and preponderance of positive as well as negative events. PMID- 8472945 TI - White coat: to wear or not to wear? PMID- 8472946 TI - Wearing a white coat. PMID- 8472947 TI - Toga alba. PMID- 8472948 TI - An optical scan/statistical package for clinical data management in C-L psychiatry. AB - This paper explores aspects of the need for clinical database management systems that permit ongoing service management, measurement of the quality and appropriateness of care, databased administration of consultation liaison (C-L) services, teaching/educational observations, and research. It describes an OPTICAL SCAN databased management system that permits flexible form generation, desktop publishing, and linking of observations in multiple files. This enhanced MICRO-CARES software system--Medical Application Platform (MAP)--permits direct transfer of the data to ASCII and SAS format for mainframe manipulation of the clinical information. The director of a C-L service may now develop his or her own forms, incorporate structured instruments, or develop "branch chains" of essential data to add to the core data set without the effort and expense to reprint forms or consult with commercial vendors. PMID- 8472949 TI - Sequence analysis of the phage 21 genes for prohead assembly and head completion. AB - Phage 21 is a temperate lambdoid coliphage, and its head-encoding genes, as well as those of phage lambda, are descended from a common ancestral phage. The head protein-encoding genes of phage 21 have been sequenced, confirming earlier genetic studies indicating that the head-encoding genes of 21 and lambda are analogous in location, size, and function. The phage 21 head-encoding genes identified (and their lambda analogues) include: 3(W), 4(B), 5(C), 6(Nu3), shp (D), 7(E), and 8(FII), respectively. An open reading frame, orf1, is analogous in position and shares some sequence identity with FI, a phage lambda gene involved in DNA packaging. The phage 21 major head protein, gp7, is predicted to have strong sequence identity (65%) with the lambda major capsid protein, gpE, including amino acids known to be important for capsid form determination. The nested genes 5/6 of phage 21 and C/Nu3 of lambda differ by several rearrangements including deletions and a triplication. The possibility that lambda genes C/Nu3 evolved from ancestal nested genes containing a triplication is discussed. PMID- 8472950 TI - Overproduction and single-step purification of GAL4 fusion proteins from Escherichia coli. AB - A DNA fragment encoding the yeast GAL4 transcriptional activator DNA-binding domain (amino acids 1-93) was cloned into an Escherichia coli expression vector such that the overproduced protein is tagged with six histidine residues and a factor Xa protease cleavage site. The vector also contains unique restriction sites at the 3' end of the gene to allow the construction of fusion proteins. These fusion proteins can easily be purified to homogeneity and their activity tested in vitro. PMID- 8472951 TI - Deletion mutations in the speED operon: spermidine is not essential for the growth of Escherichia coli. AB - Null mutants of Escherichia coli were constructed that cannot synthesize spermidine, because of deletions in the gene encoding S-adenosylmethionine decarboxylase. These mutants are still able to grow at near normal rates in purified media deficient in polyamines. These results in E. coli differ from recent findings that null mutants of Saccharomyces cerevisiae and of Neurospora crassa have an absolute growth requirement for spermidine. PMID- 8472952 TI - Cloning and sequencing of two new fli genes, the products of which are essential for Salmonella flagellar biosynthesis. AB - We have identified two new open reading frames downstream from fliC, which appear to encode 19- and 20-kDa proteins that are essential for flagellar formation. The nucleotide and the predicted amino acid sequences of the genes are presented. Both genes, termed fliU and fliV, are preceded by the flagellar-specific -10 consensus promoter DNA sequence, suggesting their expression in the earlier stages of flagellar-component biosynthesis. PMID- 8472953 TI - Organization of the genes encoding p-aminobenzoic acid synthetase from Streptomyces lividans 1326. AB - Genes involved in the biosynthesis of p-aminobenzoic acid (PABA) in Streptomyces lividans 1326 were cloned in pBR322 by complementing a pabB mutant of Escherichia coli. A 2.7-kb BamHI-SstI fragment of the cloned DNA complemented pabA and pabB mutations in both E. coli and S. lividans; complementation in S. lividans was accompanied by integration of the recombinant plasmid into the host chromosome. The nucleotide (nt) sequence of the 2.7-kb fragment contained two open reading frames, the deduced amino acid sequences of which were similar to those of pabA and pabB products from other bacteria. The nt sequences indicated that pabA and pabB are closely linked in S. lividans and supported cloning evidence that the genes are expressed from a promoter with features resembling those of most E. coli promoters. PMID- 8472954 TI - The pab gene of Streptomyces griseus, encoding p-aminobenzoic acid synthase, is located between genes possibly involved in candicidin biosynthesis. AB - The nucleotide (nt) sequence of the gene (pab) encoding p-aminobenzoic acid (PABA) synthase, a key enzyme in the biosynthesis of candicidin by Streptomyces griseus IMRU3570, was determined and an open reading frame (ORF) of 2171 nt was found. The predicted amino acid sequence demonstrated extensive sequence identity with PABA synthases (Pab) from Gram-negative Enterobacteria. The protein encoded by ORF pab shows a clear relationship at the N terminus with PabA and at the C terminus with PabB from Escherichia coli, Serratia and Klebsiella. We also determined the extent of a spontaneous deletion that removed the ORF located upstream from pab near the 5' end of the cloned fragment. The deletion occurred when the gene was cloned in the BamHI site of pBR322 and allowed pab expression in E. coli. PMID- 8472955 TI - A cloned replicon of Saccharopolyspora phages JHJ-1 and JHJ-3 is stably maintained as a plasmid in various actinomycetes. AB - A replicon of phage JHJ-1 (and JHJ-3) was cloned. The autonomously replicating phage element was maintained as a medium-copy-number shuttle plasmid in many actinomycetes, and was efficiently transmitted to spores without antibiotic selection. One gene was shown to be expressed in a vector containing the JHJ-3 replicon. PMID- 8472956 TI - The lumazine protein-encoding gene in Photobacterium leiognathi is linked to the lux operon. AB - The nucleotide (nt) sequence of the lumP (EMBL accession No. X65612) gene of Photobacterium leiognathi PL741 was determined and the amino acid (aa) sequence deduced. The encoded aa sequence of lumP was identified as that of the lumazine protein (LumP) by homology with that of Photobacterium phosphoreum (56%). This small protein has a calculated M(r) of 19,997 and comprises 186 aa residues. Biochemical studies suggested that LumP is the protein which, when combined with luciferase, is responsible for the bioluminescent spectrum shift from blue-green light (490-505 nm) to blue (470 nm) in P. leiognathi. The nt sequence of the flanking region showed that lumP is linked to the lux operon but runs in the opposite direction. The gene order of the lumP and lux operon is as follows: <- lumP-R&R-luxC-luxD-luxA-luxB-luxN-lu xE-->; the R&R regulatory region sequence included two promoter systems, PR for the lux operon and PL for the lumP or the lum operon. PMID- 8472957 TI - Sequence of the luxD gene encoding acyltransferase of the lux operon from Photobacterium leiognathi. AB - The nucleotide sequence of luxD (EMBL accession No. X65611), encoding acyltransferase (ACT), of the lux operon from Photobacterium leiognathi PL741 was determined, and the amino acid (aa) sequence was deduced. ACT is a component of the fatty acid reductase complex, which is responsible for converting fatty acid to aldehyde that serves as the substrate in the luciferase-catalyzed bioluminescent reactions. The protein has a calculated M(r) of 34,384 and comprises 305 aa residues. Alignment and comparison of the ACT of P. leiognathi with that of Vibrio fischeri ATCC7744, V. harveyi B392 and Xenorhabdus luminescens Hm shows that there is 66%, 59% and 61% aa identity, respectively. PMID- 8472958 TI - Sequence of a newly identified Mycobacterium tuberculosis gene encoding a protein with sequence homology to virulence-regulating proteins. AB - Analysis of the nucleotide sequence of a gene cloned from a Mycobacterium tuberculosis H37Rv genomic library predicted a 339-amino-acid protein with an M(r) of 37,656. The protein exhibited significant homology with the Cfad, FapR and Rns proteins from different enterotoxigenic strains of Escherichia coli, VirF protein of Shigella and VirFy protein of Yersinia, all of which regulate virulence-associated genes. PMID- 8472959 TI - A chromosomal expression vector for Escherichia coli based on the bacteriophage Mu. AB - A new Escherichia coli expression vector with increased stability was developed based on bacteriophage Mu. Unlike traditional expression vectors, the vector described herein is chromosome based rather than existing as an autonomously replicating plasmid. The chromosomal location resulted in extreme stability of the vector even in the absence of selective pressure. Both replication and heterologous protein synthesis could be induced by temperature shift. Expression of the heterologous gene was controlled by the Mu middle promoter and was dependent on the presence of the transactivator, Mor, of the Mu middle promoter. Four proteins, beta-galactosidase, chloramphenicol acetyltransferase, porcine somatotropin and human growth hormone, were made from this vector at levels ranging from 5 to 20% of total cell protein. Expression from the middle promoter was highest when inductions were done in rich media. The expression of some genes varied in different strains. PMID- 8472960 TI - A method for the site-directed mono- and multi-mutagenesis of double-stranded DNA. AB - A general solid-phase method for the site-directed mutagenesis of double-stranded DNA (dsDNA) is described. Plasmid DNA is linearized using either a restriction endonuclease (ENase) or the RecA-assisted ENase or RecA-AC cleavage method. Alternatively, PCR may be used to generate linear dsDNA. One or both strands of the DNA is biotinylated and attached to a solid support, and the DNA strands are separated using 0.2 M NaOH. An extension oligodeoxyribonucleotide (oligo) and a single or multiple oligo(s) containing the desired mutation(s) are annealed to one of the bound DNA strands and used to initiate the synthesis of a complementary strand by a nonstrand-displacing DNA polymerase. The in vitro synthesized strand incorporating the desired alteration(s) is melted off of the support and recircularized using one of several types of bridging oligos, DNA ligase, and a DNA polymerase and transformed into the host. Greater than 90% mutagenic efficiency has been obtained using this method. PMID- 8472961 TI - Genetic organization and sequence of the region encoding integrative functions from Lactobacillus gasseri temperate bacteriophage phi adh. AB - A 2.0-kb fragment from the Lactobacillus gasseri temperate bacteriophage phi adh contained the essential genetic determinants for site-specific integration. The nucleotide sequence of this fragment was determined. An open reading frame (intG), which adjoined the phage attachment site (attP), encoded a deduced protein related to the integrase family. The organization of this region was comparable to other phage site-specific recombination systems. PMID- 8472962 TI - Overproduction of Anabaena 7120 ribulose-bisphosphate carboxylase/oxygenase in Escherichia coli. AB - As a prerequisite to protein engineering, we have overexpressed the rbcLS operon of the cyanobacterium Anabaena 7120, in Escherichia coli. The operon encodes the large and small subunits of ribulose-bisphosphate carboxylase/oxygenase (Rubisco). Levels of active enzyme exceed 6% of soluble protein. We noted an apparent third gene, an unidentified open reading frame (URF) referred to here as rbcX, in the 558-bp intergenic space between the large and small subunit encoding genes. The URF, rbcX, has no known function. High-level production of Rubisco activity from the rbc operon in E. coli required simultaneous overproduction of the GroESL chaperonins under a regimen of limited growth, in contrast to more modest conditions which suffice for efficient production of the Anacystis nidulans cyanobacterial Rubisco. Deletion of rbcX or inversion of the rbcL-rbcS order did not enhance expression levels. The recombinant Rubisco, purified to near homogeneity, exhibited functional properties [Km(ribulose-P2), kcat, transition-state-analogue binding stoichiometry/exchange, and specificity factor] essentially identical to those of the enzyme obtained from Anabaena. PMID- 8472963 TI - Propagation of phage Mu in IHF-deficient Escherichia coli in the absence of the H NS histone-like protein. AB - Integration host factor (IHF) is known to be required for the expression of early genes and formation of the transpososome of mutator phage Mu. Prophage Mucts62 was stably maintained at 30 degrees C and proliferated effectively after thermal induction at 42 degrees C in an Escherichia coli mutant defective in the histone like H-NS and IHF proteins. No IHF activity was detected in cells lacking H-NS and IHF; cells could not be transformed with plasmid pCL1920, which is based on the pSC101 replicon whose replication requires IHF. No difference in the superhelical densities of the reporter plasmid was detected in the H-NS, IHF null mutant and parental cells. From these results it is concluded that IHF is not essential for Mu development. These results also suggest that H-NS may function as a silencer for Pe operon expression and that IHF overcomes the inhibitory effect of H-NS. PMID- 8472964 TI - Overproduction, purification, and characterization of DNA-binding protein P19 of bacteriophage PRD1. AB - The early protein, P19, of bacteriophage PRD1 was purified after overexpression of the cloned gene, XIX, in Escherichia coli DH5 alpha cells. The purified protein binds as multimers to single-stranded DNA (ssDNA), and with a lower affinity to double-stranded DNA (dsDNA), without sequence-specificity. Two distinct P19-ssDNA complexes were discovered in gel- mobility-shift assays at different protein:DNA ratios. P19 was capable of fully protecting ssDNA against nuclease P1. Electron microscopy of protein P19-ssDNA complexes showed DNA molecules which were extensively coated with protein and whose contour length was clearly reduced by P19 binding. The results suggest that P19 binds to ssDNA with moderate cooperativity and are consistent with the DNA being wrapped around the P19 multimers. PMID- 8472965 TI - Synthetic biomaterials in facial plastic and reconstructive surgery. PMID- 8472966 TI - Recent advances and trends in the management of maxillofacial and frontal trauma. PMID- 8472967 TI - Bone inductive biomaterials in facial plastic and reconstructive surgery. PMID- 8472968 TI - Advances in surgical hair restoration. PMID- 8472969 TI - Surgical tissue adhesives in facial plastic and reconstructive surgery. PMID- 8472970 TI - Current concepts in cutaneous laser surgery. PMID- 8472971 TI - Facial nerve regeneration, growth factors, and return of the mimetic, symmetrical smile. PMID- 8472972 TI - Presurgical orthopedic treatment for cleft lip and palate. PMID- 8472973 TI - Molecular biology of colorectal neoplasia. PMID- 8472974 TI - Helicobacter pylori: 10th anniversary of its culture in April 1982. PMID- 8472975 TI - Mechanisms underlying the antireflux action of fundoplication. AB - The effect of fundoplication on patterns of gastro-oesophageal reflux and the underlying motor mechanisms were investigated in 18 patients with symptomatic reflux. Oesophageal motility and pH were recorded concurrently after a standard meal. Studies were performed preoperatively and from 5 to 27 months after surgery. Fundoplication virtually eliminated reflux in all but three patients. Control of reflux was associated with a 50% fall in the number of transient lower oesophageal sphincter relaxations, a fall in the proportion of transient lower oesophageal sphincter relaxations accompanied by reflux from 47% to 17%, and an increase in the mean residual pressure at the gastro-oesophageal junction during swallow induced lower oesophageal sphincter relaxation from 0.7 mm Hg to 6.0 mm Hg. Basal pressure at the gastro-oesophageal junction rose from 10.9 mm Hg to 14.5 mm Hg, however, there was no correlation between postoperative reflux and basal gastro-oesophageal junction pressure. These findings suggest that the anti reflux effects of fundoplication result from changes in the mechanical behaviour of the gastro-oesophageal junction that result in incomplete abolition of the high pressure zone during lower oesophageal sphincter relaxation, and reduced triggering of transient lower oesophageal sphincter relaxations. PMID- 8472976 TI - Determinants of oesophageal 'alkaline' pH environment in controls and patients with gastro-oesophageal reflux disease. AB - The determinants of the oesophageal alkaline pH environment are poorly understood. Saliva (pH 6.4-7.8) may be a major contributor, although some argue the importance of refluxed alkaline duodenal contents. Acid and alkaline reflux parameters were studied over 2 days in 30 subjects (control, oesophagitis and Barrett's patients; 10 each) using glass pH electrodes. In phase 1, one pH electrode was placed 1 cm below the upper oesophageal sphincter to assess the influence of saliva and the other 5 cm above the lower oesophageal sphincter. Phase 2 was identical except that one pH probe was 5 cm below the lower oesophageal sphincter to record duodenogastric reflux. Patient groups spent, on average, 50 fold more time during the upright and supine periods at acidic pH than controls. Saliva was responsible for the percentage of time the pH > 7 and contributed significantly to the percentage of time the pH > 6 in both the proximal and distal oesophagus of control subjects, as shown by an absence of pH > 7 and a significant (p < 0.001) fourfold decrease in pH > 6 during sleep. A similar pattern was seen in the proximal oesophagus of both reflux groups. The reflux and Barrett's patients, however did not show a significant decrease in the percentage of time the pH > 6 at night in the distal oesophagus suggesting a relative increase in 'alkaline' exposure from another source. This was not because of duodenogastric reflux as the corresponding pH rises in the fundus of the stomach were non-existent. Although this was not studied specifically, it is believed to be a protective meachanism, the result of alkaline secretion produced by submucosal oesophageal glands. PMID- 8472977 TI - Oesophageal motor response to reflux is not impaired in reflux oesophagitis. AB - Whether the oesophageal motor response to reflux, as recorded over 24 hours, is impaired in patients with reflux oesophagitis was investigated. Twenty three patients with oesophagitis (Savary-Miller grades I-IV) and 23 control subjects matched for age and sex underwent 24 hour ambulatory pH and pressure monitoring. All contractions occurring in the 2 minute period after the onset of each reflux episode were analysed automatically using dedicated computer algorithms. A total of 2085 reflux episodes occurred--1513 in patients and 572 in controls. Oesophageal acid exposure was greater (p < 0.01) in patients than in controls (mean (SEM) % time pH < 4 13.3 (1.7) and 5.3 (0.9)%, respectively). The mean duration of the supine reflux episodes was longer (p < 0.01) in patients (11.2 (2.8) minutes) than in controls (5.1 (1.8) minutes). In the upright period, no significant differences in the motor response to reflux were found. In the supine period, the patients showed a higher number of reflux induced contractions (4.40 (0.61) v 1.62 (0.31), p < 0.01), a higher contraction amplitude (4.55 (0.42) v 2.99 (0.71) kPa, p < 0.02) and longer contractions (1.86 (0.19) v 1.32 (0.29) seconds, p < 0.05). The percentages of peristaltic and simultaneous contractions that occurred in response to supine reflux did not differ between the two groups. In patients with reflux oesophagitis the motor response of the oesophagus to reflux is not impaired. During the supine period the response is even stronger than in healthy controls. PMID- 8472978 TI - Cholecystokinin in the control of gastric acid secretion in man. AB - This study was designed to determine the role of cholecystokinin in the control gastric acid secretion in men using loxiglumide, a specific cholecystokinin receptor blocker. Three groups of healthy subjects (A, B, and C) were used; group A--for studies with postprandial gastric secretion, group B--for studies with exogenous gastric secretagogues and group C--for 12 hour intragastric pH-metry. Cephalic phase stimulated by modified sham feeding in group A subjects increased gastric acid secretion to about 50% of pentagastrin maximum and the treatment with loxiglumide in a standard dose (20 mumol/kg iv loading dose plus infusion of 20 mumol/kg/h afterwards) failed to affect this secretion. Gastric acid response to a 5% peptone meal instilled intragastrically greatly enhanced gastric acid secretion and plasma gastrin concentration but the addition of loxiglumide in the standard dose resulted in further increase in both gastric acid and plasma gastrin responses to peptone meal. Infusion of caerulein in gradually increasing doses (15-120 pmol/kg/h) and gastrin releasing peptide (25-200 pmol/kg/h) resulted in a dose dependent stimulation of gastric acid secretion reaching about 35% and 25% of maximum attained with pentagastrin. When loxiglumide was added in a standard dose, the acid responses to caerulein and gastrin releasing peptide were further increased two to three fold attaining the peak reaching, respectively, about 100% and 50% of pentagastrin maximum. In group C subjects, 12 hour pH-metry revealed the usual increase in gastric pH after each meal in tests with placebo. Loxiglumide (1200 mg tablets tid, po) resulted in significantly lower pH after each meal and this was accompanied by significantly higher gastrin responses than in placebo tests. We conclude that cholecystokinin released by peptone meal, ordinary meals or gastrin releasing peptide exerts a potent inhibitory influence on gastric acid secretion and gastrin release in men and this inhibition involves subtype A cholecystokinin receptors. PMID- 8472979 TI - Role of eicosanoids, nitric oxide, and afferent neurons in antacid induced protection in the rat stomach. AB - The mechanism underlying the mucosal protective effect of antacids is still unclear. This study shows that in rats the aluminum containing antacid, hydrotalcit, induces dose dependent protection against gastric mucosal damage caused by ethanol or indomethacin which is considerably enhanced by acidification. Hydrotalcit did not increase gastric mucosal formation or the intraluminal release of prostaglandins, and did not prevent the increase in mucosal leukotriene C4 formation in response to ethanol. Pretreatment with indomethacin did not attenuate the protective effect of unmodified or acidified hydrotalcit. Furthermore, hydrotalcit significantly reduced the gastric damage caused by indomethacin even when it was administered up to 2 hours after the ulcerogen. In indomethacin treated rats, simultaneous administration of hydrotalcit did not affect the concentrations of indomethacin in serum or inflammatory exudates nor did it attenuate the inhibition of prostaglandin release into the exudates. In hydrotalcit treated rats there was no attenuation of the increase in sulphidopeptide leukotriene release or decrease in leukocyte influx into inflammatory exudates elicited by indomethacin administration. Functional ablation of afferent neurons and inhibition of endogenous nitric oxide partially antagonised the protective effect of unmodified, but not of acidified, hydrotalcit. It is concluded that (i) the protective effect of unmodified and acidified hydrotalcit is independent of the eicosanoid system; (ii) protection against indomethacin induced gastric lesions does not require treatment before dosing of the ulcerogen and does not interfere with absorption and anti inflammatory actions of indomethacin; (iii) endogenous nitric oxide and afferent neurons contribute partly to the effect of unmodified, but not of acidified, hydrotalcit suggesting that different mechanisms mediate their mucosal protective activity. PMID- 8472980 TI - Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens. AB - Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate. PMID- 8472981 TI - Endoscopic injection therapy to prevent rebleeding from peptic ulcers with a protruding vessel: a controlled comparative trial. AB - Seventy five patients with severely bleeding peptic ulcer were included in a controlled comparative trial to assess the efficacy and safety of endoscopic injection therapy in preventing rebleeding from peptic ulcers that presented at endoscopy with a protruding vessel. Twenty five patients were treated with injection of epinephrine followed by polidocanol, 25 were treated with injection of absolute alcohol, and 25 with sham injection. Rebleeding occurred in 44% of patients in the sham group, 40% of those treated with epinephrine and polidocanol, and in 20% of those treated with absolute ethanol. The difference in the haemostasis rate between the control and ethanol treated subjects nearly reached significance (p = 0.07). A second therapy session resulted in haemostasis rates of 68% in the epinephrine-polidocanol group and of 88% in the absolute ethanol group. These rates after two treatments as well as the emergency surgery rates (32% in the epinephrine-polidocanol group and 8% in the absolute ethanol group; p = 0.07) were not significantly different. In eight of the 11 patients with rebleeding in the sham treatment group, definitive haemostasis was achieved by elective injection therapy. Overall transfusion requirements were mean (SD) 6.0 (0.7) units in the sham group, 6.0 (0.9) in the epinephrine-polidocanol group, and 3.9 (0.5) in the absolute ethanol group. Only the difference between ethanol and sham was significant (p = 0.02). This study shows that injection with absolute ethanol reduces rebleeding in these patients and significantly lowers transfusion requirements. Absolute ethanol was superior to epinephrine polidocanol, which was not significantly better than sham therapy. PMID- 8472982 TI - Secretor status and Helicobacter pylori infection are independent risk factors for gastroduodenal disease. AB - The hypothesis that non-secretors of ABO blood group antigens, a group shown to be more susceptible to certain bacterial infections, may be at greater risk of gastroduodenal disease because of increased susceptibility to Helicobacter pylori infection was investigated. Of 101 patients with symptoms of dyspepsia who were undergoing endoscopy, 32% were non-secretors (determined from Lewis blood group phenotype), 36% had endoscopically visible gastroduodenal disease (antral gastritis, gastric ulcer, erosive duodenitis, duodenal ulcer or some combination), and 58% had H pylori detected in antral biopsy specimens. Non secretors and patients with H pylori infection were significantly more likely to have gastroduodenal disease (p = 0.02 and p = 0.002 respectively). There was, however, no significant association between secretor status and H pylori infection, logistic regression analysis confirming that these were independently associated with gastroduodenal disease. Overall, the relative risk of gastroduodenal disease for non-secretors compared with secretors was 1.9 (95% confidence intervals 1.2, 3.2). Non-secretion of ABO blood group antigens is not related to H pylori infection but is independently and significantly associated with endoscopic gastroduodenal disease. The mechanism of this remains to be explained. PMID- 8472983 TI - Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. AB - The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease. PMID- 8472984 TI - Does the fatty acid profile of dietary fat influence its trophic effect on the small intestinal mucosa? AB - To compare the enterotrophic effects of different triglycerides, five groups of eight rats were fed mixed diets giving 50% of calories as oils rich in either essential fatty acids (EFA), alpha-linolenic acid, fully saturated fatty acids, oleic acid, or medium chain fatty acids. After 21-24 days there were no significant differences between the groups in overall small intestinal whole gut weight, mucosal weight, or mucosal DNA; overall mucosal protein showed slight variation (p < 0.05) that was compatible with differences in food intake between the groups. However, long chain triglycerides (LCT) and medium chain triglycerides (MCT) differed in their regional effects on cell proliferation; all four LCT rich diets increased mucosal mass and cell proliferation maximally in the mid small intestine, while MCT had their greatest effect proximally. Subsequently, two groups of eight rats were fed diets in which EFA or MCT were given as twice daily boluses (29% of dietary calories) for 20 to 23 days and compared with a third group of eight rats receiving a glucose rich, low fat diet. EFA and MCT boluses increased the overall parameters of small intestinal mucosal mass and for both oils the effects were now maximal in the mid small intestine. Thus different triglycerides have similar effects on overall small intestinal mucosal mass, but MCT differ from LCT in their regional effects on mucosal cell proliferation when they are given in mixed diets, although not when given as boluses. PMID- 8472985 TI - Effects of dietary calcium and phosphate on the intestinal interactions between calcium, phosphate, fatty acids, and bile acids. AB - Luminal free fatty acids and bile acids may damage the colonic epithelium and stimulate proliferation, which may increase the risk of colon cancer. It has been suggested that only soluble calcium ions (Ca2+) precipitate fatty acids and bile acids, thus reducing their lytic activity. Consequently, precipitation of luminal Ca2+ by dietary phosphate should inhibit these effects. To evaluate the proposed antagonistic effects of dietary calcium and phosphate, we studied the intestinal interactions between calcium, phosphate, fatty acids, and bile acids in rats fed purified diets that differed only in the concentrations of calcium and phosphate. Increased dietary calcium drastically decreased the solubility of fatty acids in the ileum, colon, and faeces, as well as the solubility of bile acids in the colon and faeces. Although dietary calcium strongly increased the total faecal fatty acid concentration and hardly affected the total faecal bile acid concentration, the fatty acid and bile acid concentrations in faecal water were drastically decreased by dietary calcium. Consequently, the lytic activity of faecal water was decreased. Dietary phosphate did not interfere with these intestinal effects of calcium. These results indicate that dietary phosphate does not inhibit the protective effects of dietary calcium on luminal solubility and the lytic activity of fatty and bile acids. PMID- 8472986 TI - Antibodies to Mycobacterium paratuberculosis and nine species of environmental mycobacteria in Crohn's disease and control subjects. AB - Cultural and serological studies have provided limited, often conflicting, evidence of a role for mycobacteria in the pathogenesis of Crohn's disease. Interest has focussed on Mycobacterium paratuberculosis, previously considered to be common in the environment with no major role as a human pathogen. Whether a specific serum antibody response to mycobacteria occurs in Crohn's disease or ulcerative colitis was investigated. Sera from patients with Crohn's disease (n = 38), ulcerative colitis (n = 15), and a healthy control population (n = 30) were assayed in an enzyme linked immunosorbent assay (ELISA) using eight filtered sonicate mycobacterial preparations and a purified protein derivative made from the bovine tubercle bacillus. In addition, IgG, IgM, and IgA levels to M paratuberculosis were determined in sera from patients with active (n = 24) or inactive (n = 29) Crohn's disease and the control populations. There was strong evidence of contact with environmental mycobacteria in all patients and control populations, with the greatest responses to preparations of M avium, M tuberculosis, and M kansasii. A large proportion of patients with Crohn's disease had antibodies that bound most antigens tested but there were no statistical differences between these values and those of the control population. Similarly, there were no differences in antibody levels to M paratuberculosis in patient and control groups. Although a subset of patients with active Crohn's disease (25%) had IgG concentrations that exceeded the control mean by more than 2 SD, this phenomenon may not be specific to Crohn's disease: 20% of a small group of patients with coeliac disease had similarly raised IgG levels to M paratuberculosis. These findings do not provide serological evidence of a role for this organism in the pathogenesis of Crohn's disease. PMID- 8472987 TI - Early mucosal changes in Crohn's disease. AB - Aphthoid ulceration has been regarded as an early macroscopic feature of Crohn's disease, yet the cause of this mucosal lesion is unknown. Examination of areas of apparently normal and non-inflamed bowel in Crohn's disease has allowed the identification of mucosal changes which occur before macroscopic and microscopic ulceration. Thirty five resection specimens from patients with Crohn's disease were compared with 12 specimens from patients with ulcerative colitis and 13 controls. Specimens were fixed either by immersion in formalin in the routine way or by perfusion fixation with formalin at mean arterial pressure. Immunostaining for macrophages, vessel wall, and blood constituents allowed identification of small mucosal capillaries which were not apparent otherwise. In Crohn's disease damage and rupture of these small capillaries occurred before infiltration of the lamina propria by inflammatory cells. Loss of the overlying epithelium seemed to follow this vascular damage. PMID- 8472988 TI - Diversion colitis and involution of the defunctioned anorectum. AB - To measure the effects of defunction in the anorectum, 12 patients (seven men and five women aged 59 (44-81) years) were studied after the Hartmann operation. The operation was for septic complications of diverticular disease in nine and sigmoid carcinoma in three patients. Physiology studies were undertaken 1 and 3 months after surgery, and diversion colitis was assessed endoscopically and by mucosal biopsy at 3 months. There was no change in anal sphincter function by three months. Proctometrogram studies, however, showed an appreciable decrease in rectal volume in all cases, by a mean of 35% of the 1 month volume. The maximum tolerable volume at 1 month was 157 (111-210) ml and at 3 months 87 (71-145) ml; p < 0.01. There was no change in rectal sensation or compliance. Erythema and granularity without gross erosions or ulceration were found at endoscopy. Histology showed abnormalities in all cases by 3 months. The characteristic features were of a chronic inflammatory cell infiltrate with surface exudate, microscopic erosions, and lymphoid follicular hyperplasia. Crypt abscesses were not a feature at this stage and there was no distortion of crypt architecture. After defunction the previously normal rectum is affected by diversion colitis which, at 3 months, is mild but has characteristics that distinguish the changes from those of inflammatory bowel disease. It is associated with progressive rectal stump involution. PMID- 8472989 TI - High frequency of K-ras mutations in sporadic colorectal adenomas. AB - The frequency of activating mutations at codons 12 and 13 of the K-ras gene was investigated in 57 sporadic adenomas from 47 patients using the polymerase chain reaction and oligonucleotide hybridisation assay. Sixty eight per cent of the adenomas tested were positive for K-ras mutations. This high frequency, combined with the lack of a correlation between mutations and adenoma size, suggest that K ras mutations occur earlier in the adenoma-carcinoma sequence than has previously been suggested. The high frequency observed in sporadic adenomas contrasts with the reported low frequency (18%) in adenomas from patients with familial adenomatous polyposis (FAP), suggesting a possible difference in the molecular genesis of FAP and non-FAP adenomas. Finally, it was found that adenomas from patients with a personal history of colorectal cancer were more likely to contain a K-ras mutation than those from patients with no such history. This is a new finding and worthy of further study. PMID- 8472990 TI - Autonomic dysfunction in gastrointestinal motility disorders. AB - The records of 113 consecutive patients with a suspected gastrointestinal motility disorder referred between January 1988 and July 1991 were retrospectively reviewed. The aims were to identify the prevalence of autonomic dysfunction in those with or without associated neurological disease and to determine the diagnostic value of testing for autonomic dysfunction. All patients had gastrointestinal manometry (3 hours fasting, 2 hours fed), 94 of 113 underwent testing of sympathetic adrenergic and cholinergic function and cardiovagal cholinergic function. All tests were scored in a standard manner. There was a significant (p < 0.05) but modest (r = 0.28) rank correlation between autonomic and motility scores. This correlation was stronger (r = 0.67, p = 0.01) in diabetic patients. The number of patients in each group with autonomic dysfunction was as follows: irritable bowel syndrome nine of 33, idiopathic upper gastrointestinal dysmotility six of 21, diabetes mellitus nine of 13, identified non-diabetic neurological syndromes six of nine, postvagotomy or abdominal surgery three of 11, and myopathic pseudo-obstruction two of seven. Autonomic testing is useful in the assessment of autonomic involvement outside the gastrointestinal tract. Logistic discriminant analysis showed that autonomic function testing did not add to the diagnostic value of motility tests in distinguishing between patients with and without irritable bowel syndrome, although a slight improvement was indicated for identifying neuropathic dysmotilities. Thus, the aetiological role of general autonomic dysfunction in irritable bowel syndrome and idiopathic and postvagotomy dysmotilities deserves further study. The addition of autonomic function tests does not add substantially to the diagnostic accuracy of clinical, radiological, endoscopic, and manometric techniques in most patients referred for evaluation of a suspected motility disorder. PMID- 8472991 TI - Radioisotope determination of regional colonic transit in severe constipation: comparison with radio opaque markers. AB - Radio-opaque markers have a well established role in distinguishing between patients with normal and those with slow intestinal transit, but in the latter group their accuracy in defining the region of delay has not been established. To study regional colonic transit accurately the transit of a radioisotope labelled meal was determined and findings were compared with those of simultaneously ingested radio-opaque markers. Twelve healthy controls (mean age 33 years) and 12 severely constipated women (mean age 36 years, bowel frequency < once per week) were studied On day 1, a meal containing 10 MBq 111In bound to 0.7 mm resin microspheres was ingested. Subjects also ingested a set of radiologically distinguishable markers on three successive days. Abdominal scans were obtained three times daily for 7 days. Abdominal radiographs were obtained after 72 or 96 hours and again at 144 or 168 hours. Eight 'regions of interest' were created- one for the small bowel, six for the colon, and one for excreted stool. The constipated patients all showed colonic transit outside the normal range, with a variable site of delay demonstrated by time activity curves for each region. To provide a different measure of the effectiveness of colonic transport, the movement of the 'centre of mass' for the radioisotope and for the markers was then determined. The radioisotope and radiopaque marker methods gave similar results. At all times between 24 and 144 hours there was no significant difference for the position of the centre of mass between the radio-opaque and marker methods. At all times, however, the mean difference between the markers and the radioisotopes was positive, indicating that the center of mass of the markers was always head of that of the radioisotope. The mean difference between the methods was never greater than one region of interest, and ranged from 12 to 72% of one region of interest in the colon. The difference between these two methods could reach up to two colonic segments in certain patients at one time. Radioisotope ingestion provides accurate information about the transit through individual colonic regions because of the possibility of frequent observations and the clear delineation of the entire colon. Although these features were not obtained with radio-opaque markers, they are suitable as a screening test for the presence and pattern of colonic delay. PMID- 8472992 TI - Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol abusers. AB - Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease. PMID- 8472993 TI - Laser lithotripsy of difficult bile duct stones under direct visual control. AB - Biliary laser lithotripsy was performed under direct visual control in 35 consecutive patients not amenable to routine endoscopy. The patients had 1-50 (median 1) bile duct stones with the greatest diameter of the largest stone being 9-42 mm (median 20 mm). Conventional endoscopic treatment had failed because of an inaccessible papilla (16 patients), biliary strictures (seven patients), and impaction or large size of calculi (12 patients). Twelve patients, depending on their anatomical condition, underwent peroral cholangioscopy by means of a mother babyscope system. Percutaneous cholangioscopy was initially carried out in 23 patients, 7-20 days (median 10 days) after creation of a transhepatic fistula. Pulsed dye laser (32 patients) or alexandrite laser (three patients) lithotripsy was applied under an appropriate direct visual control in all cases. Complete stone disintegration succeeded in 33 of 35 patients. All resultant fragments passed the papilla within a mean number of 1.3 treatment sessions. Peroral cholangioscopic lithotripsy failed in two cases. One patient successfully underwent percutaneous laser treatment and the other patient was referred to surgery. Fever, temporary haemobilia, or a subcapsular liver haematoma were seen in a total of eight patients during establishment of the cutaneobiliary fistula. A 95 year old patient who had been admitted with septic cholangitis died because of cardiorespiratory failure 5 days after bile duct clearance. It is concluded that laser lithotripsy performed under a direct visual control is an effective and safe procedure for the non-surgical treatment of difficult bile duct stones. Ductal clearance can usually be achieved in a single treatment session when the papilla and the stones are accessible by the peroral route. Percutaneous cholangioscopic lithotripsy is more time consuming but highly effective even in patients with a difficult anatomy, bile duct strictures, or intrahepatic calculi. This approach should be limited, however, to cases not amenable to retrograde procedures because the creation of the cutaneobiliary fistula is not without risks. PMID- 8472994 TI - Organising unrestricted open access gastroscopy in South Tees. AB - Increasing demand for upper gastrointestinal endoscopy has forced many clinicians to reconsider the policy of seeing all patients in a specialist clinic before gastroscopy. The following are considered essential in setting up an open access gastroscopy service. (1) Assessment of the need by examination of waiting times for the outpatient clinic and the proportion of patients requiring upper gastrointestinal endoscopy, and consultation with colleagues in general practice. During the first 2 years of the service the average waiting time for a medical gastrointestinal outpatient appointment has fallen from over 120 days to 37 days in this area. (2) An adequately staffed and equipped gastrointestinal unit with well motivated nurses (the workload will increase) and sufficient clinical support to allocate patients to the next available gastroscopy list is vital. A safe mechanism for relaying information back to the GP (including histology reports) is essential otherwise medicolegal problems could arise. Open access gastroscopy now accounts for 29% of the total endoscopy workload in South Tees. (3) Close cooperation between medical and surgical gastroenterologists must be achieved to ensure a uniform approach to the provision of this service and equal distribution of the endoscopy workload. This will require close examination of the potential numbers and may necessitate appointment of a clinical assistant or additional consultant. Clinical assistants perform just over 50% of the open access gastroscopies in South Tees and the waiting time has been kept short (average 17 days). (4) A comprehensive request form with guidelines for GPs and a specific box identifying whether the GP requires a report and brief advice only or follow up at the discretion of the endoscopist (often a clinical assistant) is required. (5) Management must be involved in identifying adequate resources. (6) Methods of monitoring requests and outcome measures to ensure effective audit must be established. PMID- 8472995 TI - Surgery for uncomplicated gastro-oesophageal reflux. PMID- 8472996 TI - Hysterectomy and the irritable bowel. PMID- 8472997 TI - Colonic tuberculosis. PMID- 8472998 TI - New theories based on inappropriate application of high technology. PMID- 8472999 TI - Acetorphan and diarrhoea. PMID- 8473000 TI - Factors affecting the distribution of ingested propionic acid in the rat forestomach. AB - Propionic acid (PA) when incorporated into food pellets and fed to male Wistar rats for 20 wk had no effect on the forestomach mucosa; however, in powdered diet PA led to pronounced hyperplasia and severe inflammatory lesions in the forestomach mucosa near the limiting ridge. Since this discrepancy in the effect of PA may have been caused by the type of diet in which PA was administered, the distribution of total PA (including the corresponding acid-soluble CoA ester) in different parts of the stomach and certain variables affecting this distribution were investigated. In the forestomachs of rats fed 4% PA in powdered diet, the amount of PA in hyperplasias (1553 +/- 508 micrograms PA/g tissue) was three times higher than that in the remainder of the tissue (479 +/- 247 micrograms PA/g tissue). The PA content decreased progressively towards the glandular parts. There was a slight, but not significant, decrease in the PA content of the forestomach and a slight increase in the PA content of the glandular stomach in rats fed pelleted food compared with those fed powdered diet. Supplementation of 1% L-carnitine to PA powdered diet for 12 wk led to a significant decrease (P < 0.02) in PA accumulation in hyperplastic tissues compared with hyperplasias induced by PA alone, although L-carnitine had no influence on the severity of hyperplastic changes in the forestomachs of rats. The present study shows that the type of diet in which PA was administered to male Wistar rats is of great importance for the development of hyperplasia, PA or the corresponding CoA ester can accumulate in the forestomach and is preferably accumulated in hyperplasias, and PA accumulation does not appear to be directly related to the severity of hyperplastic changes. PMID- 8473001 TI - Metabolism and excretion of dimethoate following ingestion of overtolerance peas and a bolus dose. AB - Data to guide an exposure assessment were obtained by giving sugar peas containing overtolerance dimethoate residues (17 ppm; 8% oxon) and a bolus dose of dimethoate to a healthy adult male. The dimethoate tolerance on peas was and remains 2 ppm. Serial total urine samples were collected and analysed for dimethoate and its oxon, dimethylphosphate, dimethylphosphorothioate (DMTP) and dimethylphosphorodithioate. The dose of dimethoate administered was approx. 0.1 mg/kg body weight and produced no symptoms of toxicity. Dimethylphosphates appeared in the urine within 2 hr. The major metabolite (about 60%) was DMTP. Only traces (< 0.5%) of dimethoate and oxon were recovered from urine. Acetylcholinesterase inhibition was not observed although urinary metabolites were prominent, indicating that they are better indicators of acute exposure than cholinesterase inhibition. The results obtained using a bolus dose were virtually identical to those from the trial with overtolerance peas, and indicated that dimethoate is readily absorbed and its urinary metabolites are readily eliminated following exposures to low doses (0.1 mg/kg body weight). PMID- 8473002 TI - Delayed effects of neonatal exposure to Tween 80 on female reproductive organs in rats. AB - Neonatal female rats were injected ip (0.1 ml/rat) with Tween 80 in 1, 5 or 10% aqueous solution on days 4-7 after birth. Treatment with Tween 80 accelerated maturation, prolonged the oestrus cycle, and induced persistent vaginal oestrus. The relative weight of the uterus and ovaries was decreased relative to the untreated controls. Squamous cell metaplasia of the epithelial lining of the uterus and cytological changes in the uterus were indicative of chronic oestrogenic stimulation. Ovaries were without corpora lutea, and had degenerative follicles. PMID- 8473003 TI - Effect of dietary T-2 toxin on biogenic monoamines in discrete areas of the rat brain. AB - Acute T-2 toxin treatments alter biogenic monoamine concentrations in the brain; however, these perturbations have not been well documented or demonstrated in feeding trials. In this study, the effect of dietary T-2 toxin on regional brain concentrations of biogenic monoamines and their metabolites was investigated in male rats fed a semi-synthetic diet containing 0, 2.5 or 10 ppm T-2 toxin for either 7 or 14 days. Reduction in feed consumption, feed efficiency and weight gain was observed in rats fed either 2.5 or 10 ppm T-2 toxin. This effect was transient in animals fed the 10 ppm T-2 toxin diet, with feed consumption, feed efficiency and weight gain improving significantly during wk 2. T-2 toxin affected brain biogenic monoamine concentrations. In the nucleus raphe magnus, serotonin, 5-hydroxy-3-indoleacetic acid and norepinephrine increased in a dose dependent manner, and dopamine increased transiently. In the substantia nigra of rats fed 10 ppm T-2, epinephrine increased after 7 days and norepinephrine decreased after 14 days, when compared with controls. Dihydroxyphenylacetic acid concentrations in the paraventricular nucleus and medial forebrain bundle were lower in T-2 toxin-treated rats than in control animals. The observed effects of T-2 toxin on brain monoamines and the resulting neurochemical imbalance may account for the physiological manifestation of trichothecene intoxication. PMID- 8473004 TI - Developmental toxicity of orally administered thiabendazole in Sprague-Dawley rats and New Zealand white rabbits. AB - The developmental toxicity of thiabendazole (TBZ) was assessed in studies in New Zealand white rabbits and Sprague-Dawley rats. The doses of TBZ for these studies were based on decreases in maternal weight gain in dose range-finding studies in pregnant females of each species. In rabbits, TBZ was administered orally at doses ranging from 24 to 600 mg/kg body weight/day in two separate studies. In rats, TBZ was administered at doses of 10, 40 or 80 mg/kg body weight/day. In all studies, TBZ was administered daily by gavage in aqueous suspension on gestation days 6 to 17. In the initial rabbit study, weight loss occurred in the 600 mg/kg/day group and weight gain decreased in the 120 mg/kg/day group. In addition, there were four complete litter resorptions and four abortions in the 120 and 600 mg/kg/day groups, respectively. To determine whether these changes (known to occur spontaneously in rabbits) were reproducible, the study was repeated. In this study, decreased maternal weight gain and decreased foetal weights were found at 600 mg TBZ/kg/day, but there was no evidence of selective developmental toxicity. Similarly, in rats TBZ produced decreased maternal weight gain (12 to 26%) associated with slight (5 to 7%) decreases in foetal weights at doses of 30 and 80 mg/kg/day. No changes were found at 10 mg TBZ/kg/day and no evidence of selective developmental toxicity or teratogenicity was found at any dose. On the basis of these results, it is concluded that TBZ is not teratogenic or selectivity foetotoxic in rats or rabbits. PMID- 8473005 TI - Effect of captopril on the cytological and biochemical changes induced by adriamycin. AB - Captopril, an angiotensin-converting enzyme inhibitor, was evaluated for its antimutagenic potential. Male Swiss albino mice (6-8 wk old) were treated orally with different doses of captopril dissolved in water for 7 days. Some of the mice in each group were injected ip with adriamycin (ADM; 15 mg/kg body weight) and killed after 30 hr. Femoral cells of mice were collected and studied for reduction of micronuclei. Proteins, RNA and DNA were determined in hepatic cells. Captopril pretreatment was found to reduce ADM-induced micronuclei in polychromatic cells and increase the quantity of protein, RNA and DNA in hepatic cells. The inhibition of clastogenicity observed may be due to free-radical scavenging action of captopril. PMID- 8473006 TI - Effects of Curcuma xanthorrhiza Roxb. and curcuminoids on the level of serum and liver lipids, serum apolipoprotein A-I and lipogenic enzymes in rats. AB - Curcuma xanthorrhiza Roxb., a medicinal plant used in Indonesia, has been shown to exert diverse physiological functions. However, little attention has been paid to its effect on lipid metabolism. We have investigated the effects of C. xanthorrhiza on serum and liver lipids, serum high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I, and liver lipogenic enzymes in rats. In rats given a cholesterol-free diet, C. xanthorrhiza decreased the concentrations of serum triglycerides and phospholipids, and liver cholesterol, and increased serum HDL-cholesterol and apo A-I. The activity of liver fatty acid synthase, but not glycerophosphate dehydrogenase, was decreased by the medicinal plant. In rats on a high-cholesterol diet, C. xanthorrhiza did not suppress the elevation of serum cholesterol, although it did decrease liver cholesterol. Curcuminoids prepared from C. xanthorrhiza had no significant effects on the serum and liver lipids. These studies, therefore, indicate that C. xanthorrhiza contains an active principle(s) other than curcuminoids which can modify the metabolism of lipids and lipoproteins. PMID- 8473007 TI - Development of an ocular irritation test in the mouse: image analysis of corneal lesions. AB - An ocular irritation test in the mouse has been developed, in which corneal lesions consecutive to instillation of ophthalmic preparations are assessed by digital image processing. The high sensitivity of this method makes it possible to test very low (i.e. therapeutic) concentrations, which do not produce macroscopic damage to the eye. The relatively low variability of the results allows the determination of irritation potential with a small number of animals. The test permits the establishment of the relationship between instilled concentrations and corneal lesions. The rapidity and simplicity of this approach make the proposed test suitable for the screening of ophthalmic preparations. PMID- 8473008 TI - What does carcinogenicity mean and how should we test for it? PMID- 8473009 TI - Interferon-gamma-activated monocytes impair infectivity of HIV particles by an oxygen metabolite-dependent reaction. AB - Mononuclear phagocytes generate microbicidal oxygen metabolites spontaneously and after phagocytic stimulation by a NADPH-dependent enzymatic reaction called the oxidative burst. The spontaneous release of reactive oxygen radicals and intermediates (ROI) increases five- to eightfold after treatment of monocytes with the lymphokine interferon-gamma (IFN-gamma). The effect of the IFN-gamma activated release of ROI by human monocytes on the infectivity of free human immunodeficiency virus (HIV) in the supernatant was investigated with the following results. First, IFN-gamma-activated, but neither control monocytes nor lipopolysaccharide-stimulated monocytes effectively decreased the infectivity of cell-free HIV-1 in culture medium supernatant. Second, the mechanism of inactivation was dependent on the enhanced spontaneous release of ROI by IFN gamma-activated mononuclear phagocytes, since either the enzyme catalase or the free radical scavenger butylated hydroxyanisole (BHA) could block this activity. Third, soluble and solid-phase HIV-1 outer envelope glycoprotein (gp120) failed to trigger the oxidative burst activity after specific gp120-monocytic CD4 receptor interaction. These results indicate an anti-viral effect of IFN-gamma activated monocytes/macrophages on HIV-1 which may have important implications for our understanding of spread of the virus in the body and the development of full-blown AIDS after a long period of latency. PMID- 8473010 TI - Interferon-gamma inhibits interleukin-8 production by human polymorphonuclear leucocytes. AB - Stimulation of human polymorphonuclear leucocytes (PMN) with phagocytosable particles [yeast-IgG (Y-IgG)], lipopolysaccharide (LPS), tumour necrosis factor (TNF) or formyl-methionyl-leucyl-phenyl-alanine (FMLP) results in an increase of the interleukin-8 (IL-8) mRNA accumulation and a subsequent release of the protein. Here, we report that interferon-gamma (IFN-gamma) down-regulates the constitutive IL-8 mRNA levels expressed by resting PMN. As shown by Northern analysis, this down-modulation occurred rapidly, was not dependent on new protein synthesis, and was not caused by an increased rate of degradation of IL-8 mRNA. Preincubation of PMN with IFN-gamma significantly inhibited their ability to release IL-8 upon stimulation with TNF, LPS, FMLP and Y-IgG, but enhanced the respiratory burst capability in response to FMLP and TNF. TNF-, LPS- and FMLP induced expression of IL-8 mRNA was also selectively inhibited by IFN-gamma. Taken together these findings suggest that IFN-gamma has important regulatory effects on acute inflammatory response because of its capacity to modulate negatively IL-8 gene expression and secretion by human PMN. Further observations revealed that, in human PMN, degradation of IL-8 mRNA is finely regulated, and that cycloheximide (CHX), an inhibitor of protein synthesis, super-induces the mRNA accumulation for IL-8 in a dose- and time-dependent manner. PMID- 8473011 TI - Contact sensitization to oxazolone: involvement of both interferon-gamma and interleukin-4 in oxazolone-specific Ig and T-cell responses. AB - The synthesis and role of several lymphokines were examined during contact sensitization to oxazolone (OX). Application of OX to the skin of mice increased the delayed-type hypersensitivity (DTH) response to challenge, serum titres of OX specific IgG1 and IgG2a, and draining lymph node cell (LNC) numbers. At day 3, LN contained detectable interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-2 or IL-3 mRNAs; IL-3 and higher levels of IL-4, IFN-gamma and GM-CSF mRNAs were measured after 24 hr culture with anti-CD3 antibody in OX-primed but not unprimed LNC. As a result of sensitization, LNC secreted IL-3 constitutively and produced elevated levels of IL-2, IL-3, IL-4 and IFN-gamma in response to anti-CD3 antibody; a similar but weaker lymphokine response was recalled by OX-protein conjugate. CD4+ cells were the major source of the anti-CD3-induced lymphokines except IFN-gamma, which was derived mainly from CD8+ cells. Since both IL-4 and IFN-gamma were synthesized by OX-primed LNC in vivo and in vitro, their role was investigated by administering anti-lymphokine antibodies at the time of sensitization. Anti-IL-4 treatment reduced OX-specific serum IgG1 titres without affecting IgG2a titres, whereas anti-IFN-gamma treatment reduced IgG2a but not IgG1 titres. Although neither antibody altered DTH responsiveness, anti-IFN-gamma treatment markedly increased IL-4 production by CD4+ LNC and reduced IFN-gamma production in vitro, particularly by CD4+ cells. We conclude that endogenous IL-4 and IFN-gamma reciprocally influence the isotype of the Ig response to OX and that IFN-gamma also affects the relative levels of IL-4 and IFN-gamma synthesis by CD4+ LNC. PMID- 8473012 TI - Interleukin-6 biosynthesis is increased by histamine in human B-cell and glioblastoma cell lines. AB - An enhancing effect of histamine on the biosynthesis and gene expression of interleukin-6 (IL-6) by human cell lines, Epstein-Barr virus (EBV)-infected human B lymphoma line BMNH and the glioblastoma line SK-MG4 has been found. No similar effect of histamine has been detected on the IL-6 production by any other B-cell line, CESS or human peripheral monocytes. Histamine stimulates the IgM production of BMNH cells by autocrine action of IL-6 induced by histamine, since either neutralization of IL-6 by polyclonal antibody or blocking the IL-6 receptor by specific monoclonal antibody abolished the effect of histamine. PMID- 8473013 TI - Transforming growth factor-beta 1 enhances polymorphonuclear leucocyte accumulation in dermal inflammation and transendothelial migration by a priming action. AB - Acute inflammatory reactions are usually characterized by polymorphonuclear leucocyte (PMNL) migration into inflamed tissues. Transforming growth factors beta 1 (TGF-beta 1) may be involved in inflammatory reactions but its actions are controversial and require further in vivo studies. We employed a rabbit dermal inflammation model to investigate the effect of TGF-beta 1 on PMNL migration induced by cytokines and chemotactic factors, using 51Cr-labelled leucocytes to quantify PMNL accumulation in dermal lesions. Injection of TGF-beta 1, over a wide dose range, alone did not elicit PMNL accumulation (0.14 x 10(6) PMNL/site). This contrasted with responses to interleukin-1 alpha (IL-1 alpha) (11.8 x 10(6) PMNL/site), tumour necrosis factor-alpha (TNF-alpha) (4.5), lipopolysaccharide (LPS) (14.9), FNLP (10.1), or IL-8 (6.6). However, when sites were pretreated for 3 hr with TGF-beta 1 (1-10 ng) and subsequently re-injected with the inflammatory stimuli, TGF-beta 1 primed the tissue for an enhanced recruitment of PMNL in response to the endothelium-activating inflammatory agents, IL-1 alpha, TNF-alpha and LPS, but not to IL-8 or FNLP, which are directly PMNL chemotactic. For example, with IL-1 alpha, PMNL accumulation was 205% greater than the additive sum of each response alone (P < 0.05). This was confirmed histologically. TGF beta 1 pretreatment enhanced PMNL accumulation over a wide dose range of IL-1 alpha and LPS. TGF-beta 1 did not alter the kinetics of IL-1 alpha or LPS-induced PMNL accumulation, but increased the peak rate of accumulation in lesions. Using an in vitro PMNL transendothelial migration system, TGF-beta 1 (10 ng/ml) was found to prime the endothelium for responsiveness to a submaximal dose of IL-1 alpha (0.005 ng/ml) or a threshold dose of LPS (0.01 ng/ml), resulting in enhanced PMNL transendothelial migration. Thus, TGF-beta 1 may have a role in priming the microvasculature for enhanced PMNL emigration, especially in response to endothelium-activating agents. PMID- 8473014 TI - Regulatory effect of interleukin-4 (IL-4) on the expression and function of lymphocyte adhesion receptors involved in IL-2-induced cell aggregation. AB - Human recombinant interleukin-4 (rIL-4) was studied for its capacity to inhibit rIL-2-induced lymphoid cell aggregation. In contrast to rIL-2, rIL-4 was unable to induce cluster formation by itself. However, when added simultaneously with rIL-2 to cultures of freshly isolated peripheral blood lymphocytes (PBL), rIL-4 inhibited cell aggregation in a dose-dependent way. In contrast, PBL, preactivated by a 4-day culture in the presence of 500 U/ml rIL-2, were not inhibited in their adhesive capacity by rIL-4. Inhibition of cell aggregation was most prominent at 24 hr and virtually lost after 72 hr of culture. Phenotypical analysis revealed that rIL-4, with similar kinetics, decreased the rIL-2-mediated up-regulation of the CD2, CD54 and CD49e adhesion molecules. In addition, it was observed that up-regulation of the activation epitope on CD11a recognized by the mAb NKI-L16, was prevented. During 24hr of culture rIL-4 itself did not alter the expression of these antigens. Blocking experiments with mAb directed against adhesion structures did not reveal a direct role for CD49e, but obviously demonstrated involvement of CD11a/CD18-CD54 and CD2-CD58 interactions in the rIL 2-induced adhesion. Therefore, rIL-4 appears to inhibit the early phase of rIL-2 induced aggregation by preventing the up-regulation of CD54 and CD2 antigens and by inhibiting the generation of the activated state of the CD11a/CD18 receptor. PMID- 8473015 TI - Diversity of functional T-cell receptor delta-chain transcripts from bone marrow cells of athymic nude mice. AB - CD3+ cells are detectable in bone marrow of athymic mice homozygous for the nude mutation. As previously shown, cells expressing the gamma delta T-cell receptor (TcR) represent 30-40% of this T-cell population. Using V delta-specific, V alpha 4-specific, and C delta-specific primers, TcR delta-chain transcripts were reverse transcribed and polymerase chain reaction (PCR)-amplified from total RNA prepared from bone marrow cells (BMC) of 6-month-old NMRI nu/nu mice. Amplified TcR delta-chain cDNA was cloned, and 49 randomly selected clones derived from seven amplification reactions were sequenced. Sequence analyses showed: (1) more than 80% of the sequenced clones represented in-frame transcripts of the TcR delta-chain; (2) in-frame transcripts containing V delta 1-, V delta 2-, V delta 3-, V delta 4-, V delta 5-, V delta 6- and V alpha 4-gene segments were detectable in nude BMC; (3) V delta 2-, V delta 4- and V delta 5-containing transcripts were more abundant and more diverse than V delta 1- and V delta 3 containing transcripts; (4) extensive N-region diversity was present in the V delta-D delta 2 (N1), D delta 2-D delta 1 (N2) and D delta 1-J delta 1 (N3) junctional regions; (5) P nucleotide additions were present in many transcripts; and (6) unusual truncated, in-frame transcripts with deleted D- and J-region genes were detected. A large potential TcR delta-chain repertoire is thus present in nude BMC. PMID- 8473016 TI - Platelet-activating factor-induced human eosinophil activation. Generation and release of cyclo-oxygenase metabolites in human blood eosinophils from asthmatics. AB - The spontaneous and stimulated generation of fatty acid cyclo-oxygenase pathway derived products of arachidonic acid from highly purified (91.6 +/- 1.3%, n = 23) human blood eosinophils obtained from asthmatics were examined using combined gas chromatography/mass spectrometry. Under resting conditions, eosinophils spontaneously generated 0.24 +/- 0.10 pg prostaglandin E2 (PGE2), 0.51 +/- 0.20 prostaglandin D2 (PGD2), 0.35 +/- 0.10 pg prostaglandin F2 alpha (PGF2 alpha) and 8.5 +/- 2.2 pg thromboxane B2 (TXB2), the stable metabolite of TXA2 per 10(6) cells. In contrast, 6-keto-prostaglandin F1 alpha and 9 alpha,11 beta prostaglandin F2 were not detectable. Stimulation of eosinophils with platelet activating factor (PAF) for 5 min induced a two- to sixfold increase in the biosynthesis of prostanoids. More than 95% of the generated prostanoids were released into the surrounding medium. The response to PAF was inhibited by the PAF receptor antagonist WEB 2086 (1 microM). The fatty acid cyclo-oxygenase inhibitor, ibuprofen, abolished both the spontaneous and PAF-stimulated generation of prostanoids by eosinophils. LTB4, PMA and calcimycin also produced an increase in prostanoid production, whereas lyso-PAF, the PAF precursor and metabolite, failed to induce prostanoid generation over basal production. In conclusion, the results demonstrate that PAF potently activates human eosinophils to generate and release several fatty acid cyclo-oxygenase metabolites of the arachidonic acid pathway, with TXB2 being the most abundant. These data are in agreement with previous observations suggesting that PAF may be an important stimulus for prostanoid release by the eosinophil in allergic diseases such as asthma. PMID- 8473017 TI - Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria. AB - The in vitro production of reactive nitrogen intermediates (RNI) by murine macrophages was evaluated in response to heat-stable malaria antigen and cytokines. Malaria antigen, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) induced RNI production in macrophages in a dose-dependent way. RNI production steadily increased over a 2-day period and was enhanced when the malaria antigen was co-incubated with IFN-gamma and/or TNF. RNI production induced by either IFN-gamma or malaria antigen or a combination of the two was suppressed by pentoxifylline in a dose-dependent manner. Pentoxifylline did not significantly influence TNF-induced RNI production. L-N-monomethyl arginine reduced malaria antigen, IFN-gamma and TNF-induced RNI production when these reagents were used in combination or alone. An anti-TNF monoclonal antibody (mAb) reduced IFN-gamma-induced RNI production, but did not significantly alter the malaria antigen-induced RNI synthesis by macrophages. The influence of inhibitors of nitric oxide synthase, L-N-monomethyl arginine and N omega-nitro-L-arginine, was studied in experimental cerebral malaria. They did not exert any significant effect on the development of cerebral malaria in Plasmodium berghei ANKA-infected CBA/J mice. PMID- 8473018 TI - IgE and IgG2a antibody responses are induced by different antigen groups of the nematode Nippostrongylus brasiliensis in rats. AB - The differences were examined between IgE, IgG1 and IgG2a antibody responses against two kinds of nematode antigens in rats infected with Nippostrongylus brasiliensis. With ELISA studies, remarkable IgE and IgG1 antibody responses were observed against antigens in excretory/secretory products (ES) of N. brasiliensis, whereas the IgG2a antibody response against ES was negligible. On the other hand, antibody response to antigens in an extract of homogenized adult worm (AW) was observed mainly in IgG2a, with little response in IgE or IgG1. Immunohistochemical studies showed that IgE- and IgG1-binding antigens were localized almost exclusively in the subventral glands, a secretory apparatus in N. brasiliensis, while IgG2a-binding antigens were found mainly in the nematode wall along the body cavity. Immunoblot analysis revealed that the major IgE- and IgG1-binding molecules in ES were identical. On the other hand, some, but not all, of the major IgG2a-binding molecules in AW were different from the IgE/IgG1 binding molecules in ES. The findings suggest that the IgE/IgG1 and IgG2a antibody responses in N. brasiliensis-infected rats are induced by different groups of nematode antigens. Thus, it is presumed that the production of each class of antibody might be dependent, at least in part, on the nature of the antigen or antigen-linked molecules. PMID- 8473019 TI - Immune-mediated alteration of the terminal sugars of goblet cell mucins in the small intestine of Nippostrongylus brasiliensis-infected rats. AB - Alteration of terminal sugars of goblet cell mucins in the small intestinal mucosa was examined by lectin histochemistry in rats infected with Nippostrongylus brasiliensis. To see whether alteration of the nature of mucins was regulated by the local immune system, adult worms were implanted intraduodenally into recipient rats of various immune status. When 7-day-old ('normal') adult worms were implanted into naive euthymic rats, about 60% remained until day 7 and then were expelled. The number of goblet cells transiently decreased on day 5 and then progressively increased from day 9 onwards. In parallel with the hyperplasia, mucins in and released from goblet cells strongly expressed terminal N-acetyl-D-galactosamine which was specifically recognized by Helix pomatia agglutinin (HPA). When 13-day-old ('damaged') adult worms were implanted into naive euthymic rats, they were rapidly expelled by day 9 in association with hastened goblet cell hyperplasia and the alteration of terminal sugars of the mucins. Hastened worm expulsion, goblet cell hyperplasia and alteration of terminal sugars of the mucins were also observed when 'normal' worms were implanted into immune recipients. On the other hand, after implantation of 'normal' worms into hypothymic (rnu/rnu) rats, goblet cell hyperplasia or the alteration of terminal sugars of the mucins was almost completely absent. These results suggest that alteration of sugar residues of goblet cell mucins, especially the strong expression of terminal N-acetyl-D galactosamine, is regulated by the host's immune system and seems to be important in the expulsion of N. brasiliensis. PMID- 8473020 TI - Influence of severe protein malnutrition on rat lacrimal, salivary and gastrointestinal immune expression during development, adulthood and ageing. AB - The objective of the present study was to examine and to compare the impact of severe protein malnutrition during development, adulthood and ageing on secretory immune expression in the eye, mouth and small intestine. In addition, we sought to determine whether potential abrogation of mucosal immunity by protein deprivation might be reversed by the administration of a balanced diet. Weanling, adult and aged rats were provided isocaloric diets containing 24% (control), 19%, 14%, 10%, 6% and/or 3.2% protein levels for defined periods and various immunological parameters were evaluated before, during and after the dietary regimen. Our results demonstrated the following. (1) Severe protein malnutrition (3.2%) dramatically suppressed the secretory immune system in eyes of weanling rats. After 8 weeks of protein insufficiency, tear IgA concentrations in young rats had undergone a precipitous decrease, such that IgA could not be detected in tears. This response was paralleled by a significant decline in the tear volume, tear secretory component (SC), IgG and total protein content, number of IgA containing cells in lacrimal tissue, as well as the amounts of SC and/or IgA in saliva, intestinal secretions and serum. In contrast, the immunological effects of protein malnutrition in adult or aged animals varied considerably depending upon the specific mucosal site. (2) The influence of protein deprivation was dose dependent and reversible: maintenance of weanling rats on 10%, 6% or 3.2% protein diets interfered with the establishment of ocular and intestinal mucosal immunity, but later administration of optimal diets to these malnourished animals permitted a rapid immune recovery. (3) The impact of protein malnutrition on tear IgA levels in weanling animals, as shown by pair-feeding experiments, appeared to reflect primarily protein deficiency and not caloric restriction. Overall, these findings show that dietary protein plays a significant, site-specific role in the developmental expression of the secretory immune system. PMID- 8473021 TI - Interaction of the terminal complement components C5b-9 with synovial fibroblasts: binding to the membrane surface leads to increased levels in collagenase-specific mRNA. AB - The late complement components, apart from their lytic function, are known to trigger the release of various proinflammatory substances from different types of nucleated cells. In the present study, the interaction of C5b-9 with synovial fibroblast cells (SFC) was examined. It was found that incubation of SFC with activated complement components resulted in binding of C5b-9 to the cell membrane; subsequently an increase in abundance of collagenase-specific mRNA was seen, as assessed by Northern blotting. When C8-deficient serum was used as source of complement neither binding of C5b-9 nor an increase in collagenase specific mRNA could be detected. These findings suggest that C5b-9, which might be generated during rheumatoid inflammation, may contribute to chronic joint destruction by triggering collagenolytic activity. PMID- 8473022 TI - Natural killer cells and tumour necrosis factor-alpha-mediated enteropathy in mice. AB - We have shown previously that normal mice given interferon-alpha/beta (IFN alpha/beta) or tumour necrosis factor-alpha (TNF-alpha) develop marked intestinal pathology which is similar to that found in enteropathies associated with cell mediated immunity in vivo, such as graft-versus-host reaction (GVHR). The enteropathy induced by IFN-alpha/beta and GVHR are both dependent on the presence of natural killer (NK) cells and here we have examined whether NK cells are also required for enteropathy caused by TNF-alpha. Mice injected with recombinant TNF alpha displayed enhanced splenic NK cell activity and developed significant villus atrophy and crypt hypertrophy in the small intestine. Administration of anti-asialo GM1 antibody abolished the NK cell activity in both normal and TNF alpha-injected mice, but had no effect on the enteropathy caused by TNF-alpha. We conclude that NK cells are not required for TNF-alpha to damage the small intestine. PMID- 8473023 TI - Measuring rates of fluid flow through dentine in vivo. PMID- 8473024 TI - New developments in confocal optical microscopy for monitoring fluid flow in dentine. PMID- 8473025 TI - Determining the internal morphology of root canals. PMID- 8473026 TI - The use of electronic apex locators in endodontic therapy. PMID- 8473027 TI - Leakage around root canal fillings. PMID- 8473028 TI - Micropuncture measurements of interstitial fluid and vascular pressures in dental pulp. PMID- 8473029 TI - Methods for assessing pulpal innervation and monitoring reinnervation. PMID- 8473030 TI - A comparison of the dentine-removing characteristics of two endosonic units. AB - The purpose of this study was to compare the dentine-removing characteristics of size 25 K-files activated by the Cavi-Endo and Piezon-Endo units. The influence of power-setting, direction of file oscillation, interfacial force and operator assisted movement were studied. Filing was performed on flat surfaces of dentine and impressions of the instrumented surfaces revealed characteristic patterns of dentine removal corresponding to the area of contact with the file which was quantified using a Reflex microscope. Differences in dentine removal as affected by the power output of the two systems were only apparent when the maximum power setting on the Cavi-Endo was compared with the maximum recommended for root canal preparation on the Piezon-Endo. The Cavi-Endo removed significantly more dentine than the Piezon-Endo. When operator-assisted movement of the file was superimposed, both systems removed significantly more dentine than without assisted filing, However, the Piezon-Endo now removed significantly more dentine than the Cavi-Endo. This difference was more apparent when the file oscillated perpendicular to the dentine surface, compared with oscillation parallel to the substrate. An increase in the interfacial force from 30 g to 60 g resulted in a greater reduction in dentine removal by the Cavi-Endo compared with the Piezon Endo. Thus, at a 30 g interfacial force there were insignificant differences between the endosonic units but at 60 g, the Piezon-Endo removed significantly more dentine than the Cavi-Endo. The dentine-removing characteristics of the two endosonic units tested are very different under certain conditions. These findings may have important clinical implications. PMID- 8473031 TI - Replication of sensitive dentine. PMID- 8473032 TI - Endodontic leakage studies reconsidered. Part I. Methodology, application and relevance. AB - An increasing number of endodontic leakage studies have been published. In the 1990 volumes of Journal of Endodontics and International Endodontic Journal, there was one leakage study to every 4.3 scientific articles. The most popular method was linear measurement of tracer (dye or radioisotope) penetration along a root filling. Comparing some data on linear measurement of dye penetration following the cold lateral condensation of gutta-percha that were published between 1980 and 1990, a high level of variation has been found, although the experimental methods used in these studies were quite similar. In almost all studies evaluating various techniques, the cold lateral condensation technique has been used as a standard control for comparison. The reliability of these results is questionable. The problems with such studies are discussed. It seems that more research should be done on leakage study methodology, instead of continuing to evaluate the sealing ability of different materials and techniques by methods that may give little relevant information. PMID- 8473033 TI - Testing sensitive dentine in man. PMID- 8473034 TI - Endodontic leakage studies reconsidered. Part II. Statistical aspects. AB - The aim of many endodontic studies is to compare two or more treatment methods, techniques or materials, for example, to detect differences in mean leakage scores. As it is not feasible to study large populations, samples are taken. The important question then arises as to how large the sample sizes have to be in order to establish the 'true' (= populations') mean scores. First, it must be determined which magnitude of the difference (= v) between the mean scores is of endodontic interest. Based upon v and a few related statistical parameters, one may calculate how large the samples must be in order that a statistical test yields a significant result for a difference that is of endodontic importance. In other words, the 'power' of a test, depending on the sample size among other factors, must be large enough to detect the 'true' a priori determined difference between the populations. The use of small sample sizes may imply that a rather large difference between two mean leakage scores is not found to be significant, thereby leading to incorrect conclusions. This article describes the power and the statistical related factors that determine the adequate size of samples. Examples of power calculation are presented. Next, the power of publicized endodontic leakage studies was evaluated. Almost two-thirds of the sample sizes were 10 or less, and about 90% were 20 or less. Less than one-half of the tests had an adequate power (conventionally > or = 0.80). It is necessary to be cautious when extrapolating the results of such studies, because of the limited power of the statistical tests. The power may be increased by using larger sample sizes or, alternatively, by enlarging the 'effect size', by either taking an interest in a larger difference between the mean scores, or by minimizing the variability of the data. PMID- 8473035 TI - Clinical measurement of hypersensitive dentine. PMID- 8473037 TI - Pulpal blood flow: use of radio-labelled microspheres. PMID- 8473036 TI - The relationship between the root canal filling and post space preparation. AB - The restoration of root treated teeth often requires the use of posts. Their use may affect the quality of the seal of the root canal filling. The various aspects of the relationship between root canal filling and post space preparation are discussed in this review. It is recommended that the use of posts should be avoided whenever possible. Where the preparation of post space is required, immediate removal of gutta-percha using heated instruments and small Gates Glidden drills is the method of choice. PMID- 8473038 TI - Monitoring blood flow changes by radioisotope clearance from a depot in a cavity in dentine. PMID- 8473039 TI - Laser Doppler technique--a future diagnostic tool for tooth pulp vitality. PMID- 8473040 TI - Advantages and limitations of laser Doppler flow meters. PMID- 8473041 TI - Relevance of DT-diaphorase activity to mitomycin C (MMC) efficacy on human cancer cells: differences in in vitro and in vivo systems. AB - Using 4 human cancer cell lines, 4 tumors xenografted into nude mice, and 11 fresh tumor specimens removed at surgery, we investigated the relevance of NAD(P)H:quinone oxidoreductase (DT-diaphorase, DTD) activity (nmoles/min/mg protein) to mitomycin C (MMC)-induced cytotoxicity. In culture cell lines, KB cells had significantly higher levels of DTD activity (8260) than PH101 (1934), SH101 (1805) or K562 (1796), and the highest sensitivity to MMC. In contrast, the higher the DTD activity of xenografts, the greater their resistance to MMC, while the inhibition rate of relative tumor growth for MMC, as evaluated by the NCI protocol, was highest in SH-6, high in CH-5, lower in CH-4 and lowest in EH-6. The investigation using 11 fresh tumor specimens also showed an inverse relationship between IC50 values after a 30-min MMC treatment, as evaluated by ATP assay and DTD activities. Moreover, a non-toxic DTD inhibitor, dicoumarol (DIC), or flavin adenine dinucleotide (FAD), suppressed the efficacy of MMC in culture cells, but enhanced it in xenografts. Thus, we suggest that DTD may play an important role in MMC-induced cytotoxicity but MMC metabolism by DTD in solid tumors may differ from that in culture cells. PMID- 8473042 TI - Altered dexamethasone responsiveness and loss of growth control in tumorigenic mouse lung cell lines. AB - Glucocorticoid hormones induce differentiation, inhibit proliferation, and, in mice, reduce carcinogen-induced tumorigenesis of lung epithelial cells. Therefore we examined dexamethasone effects on tumorigenic and non-tumorigenic mouse lung epithelial-derived cell lines. Non-tumorigenic cells were growth inhibited and exhibited CAT activity in pMMTV-CAT transfectants in response to dexamethasone. Tumorigenic cell lines exhibited a range of responses to dexamethasone. While one tumorigenic line was growth-inhibited and responsive in CAT assays, 2 other tumorigenic cell lines were unresponsive both in CAT and in growth assays. A fourth tumorigenic cell line exhibited intermediate sensitivity in CAT assays and was actually growth-enhanced by dexamethasone. Although no difference between cell lines was observed in the abundance of glucocorticoid receptor protein on Western blots, the least dexamethasone-responsive tumorigenic lines exhibited very little binding of 3H-dexamethasone. Clones of tumorigenic lines stably transfected with the rat glucocorticoid receptor gene were more dexamethasone sensitive in CAT assays and were growth-inhibited by dexamethasone. These data suggest that the neoplastic progression of cell lines derived from mouse lung frequently involves the acquisition of diminished glucocorticoid responsiveness. PMID- 8473043 TI - Conditional expression and oncogenicity of c-myc linked to a CD2 gene dominant control region. AB - Over-expression of the c-myc gene is widely implicated in the genesis of lymphoid neoplasia, including tumours of the T-cell lineage. To study the effects of deregulated c-myc expression on T-cell development and oncogenesis, we sought to generate a transgenic mouse model in which c-myc expression was targeted specifically to the T-cell lineage. A plasmid construct containing a dominant control region (DCR) from the human CD2 locus linked 5' to the human c-myc gene was used to generate 2 lines of transgenic mice. Both strains developed thymic lymphoma at low frequency, but thymic development and peripheral T-cell numbers were otherwise apparently normal. Low tumour penetrance was consistent with the observed lack of stable CD2-myc transgene mRNA in tissues of healthy transgenic mice. In contrast, transgene RNA was detected in all malignant tumours as well as in early lymphomatous lesions. RNase protection analyses confirmed these findings and showed that the PI human c-myc promoter was active in all neoplastic tissues but not in the thymus or other tissues of healthy transgenic mice. Despite the low spontaneous tumour incidence, the presence of the transgene markedly and uniformly accelerated the onset of tumours after neonatal infection with Moloney murine leukaemia virus. All tumours were rearranged for T-cell receptor beta chain genes and were of T-cell origin from their surface phenotype (Thy-1+, CD3+, CD4+/-, CD8+, sIg-). Virus-accelerated tumours contained clonal integrations of Moloney murine leukaemia virus, suggesting that proviral insertional mutagenesis may have played a role in tumour development. Analysis of several candidate myc cooperating genes failed to reveal any rearrangements apart from a low frequency involving proviral insertion at the pim-1 locus. The CD2-myc mouse should therefore be a valuable system in screening for novel myc-collaborating genes involved in T-cell lymphoma. PMID- 8473044 TI - The permissive role of oxygen-derived free radicals in the development of colonic cancer in the rat. A new theory for carcinogenesis. AB - The colonic carcinogen 1,2-dimethylhydrazine (DMH) was given to male rats at 10 weeks of age in the form of weekly s.c. injections for 28 weeks. The results obtained show that the incidence of colonic cancer is directly dependent on dietary fat intake and that carcinogens which produce colonic cancer in the presence of a high-fat diet are rendered harmless when a low-fat diet is consumed. These results suggest that dietary fat is permissive for colonic carcinogenesis. Administration of the radical scavengers allopurinol and dimethyl sulfoxide afforded dose-dependent protection against this permissive role. PMID- 8473045 TI - Descriptive epidemiology of malignant carcinoids in the Swiss Canton of Vaud. PMID- 8473046 TI - UICC Study Group on Basic and Clinical Cancer Research: genotypes and phenotypes of tumor suppressors. Meeting held at Woods Hole, MA, October 1-4, 1992. PMID- 8473047 TI - Non-melanoma skin cancer: ten years of cancer-registry-based surveillance. AB - The Tasmanian Cancer Registry carried out population-based surveillance of non melanoma skin cancer (NMSC) from 1978 to 1987. A total of 8,651 NMSC were recorded in 7,160 individuals, representing an age-standardized rate of 161/100,000 per year. Ninety-four percent of cases were based on histological diagnosis. Incidence of basal-cell carcinoma (BCC) was higher than the incidence of squamous-cell carcinoma (SCC). The incidence of NMSC was twice as high in men as in women. Incidence increased substantially with age, more markedly for SCC than BCC. For most body sites, BCC was more frequent, but on highly exposed sites such as the backs of hands, lower limbs in women and ears in men, the incidence of SCC was higher. There was an overall increase of 7% per year in the age standardized incidence rate of NMSC. The increase was more marked for BCC than for SCC, and was consistent across age groups and both sexes. A first NMSC during the study period was associated with a 12-fold increase among men and a 15-fold increase among women in the risk of development of a new NMSC within 5 years, when compared with the NMSC incidence recorded for the population as a whole. PMID- 8473048 TI - Corn and wheat-flour consumption and mortality from esophageal cancer in Shanxi, China. AB - In order to identify factors that may explain the great variation in mortality from esophageal cancer in Shanxi Province, China, an ecological study was carried out in 21 communes in that province. Mortality data were obtained from the registration records of the population of 148,928 during 1983 to 1988, which provided 744,640 person-years of observation. The data regarding average consumption of each kind of grain, potatoes and sweet potatoes were from food allocation records. The data regarding consumption of meat, eggs, fruit, vegetables and the data regarding alcohol drinking were from interviews. The concentrations of nitrite and of nitrate in pickled vegetables and in drinking water were measured. A significant positive relation was found between mortality rate and the consumption of dietary corn and wheat flour. Also, a significant inverse relation was found between the mortality rate and the dietary sorghum and millet level. The age- and sex-adjusted mortality-rate ratio of esophageal cancer for residents in the third and highest quartiles of corn- and wheat-flour consumption are 1.4 (95% CI: 1.1-2.0) and 3.2 (2.5-4.2), respectively, compared with those in the lowest quartile. Other factors studied did not contribute to the great variation in esophageal cancer mortality in the areas studied. PMID- 8473049 TI - Age-period-cohort modelling of large-bowel-cancer incidence by anatomic sub-site and sex in Connecticut. AB - In order to investigate etiologic distinctions among the anatomic sub-sites of the large bowel by sex, the relationship between large-bowel-cancer incidence and age at diagnosis, time period at diagnosis, and birth cohort was analyzed by anatomic sub-site and by sex, using data from the Connecticut Tumor Registry. Included in the study were all incident large-bowel-cancer cases occurring between 1950 and 1984 among Connecticut residents aged 40 to 79. Cancers of the large bowel were classified into 5 anatomic sub-sites: ascending colon (including cecum), transverse colon (including flexures), descending colon, sigmoid colon, and rectum (including rectosigmoid junction, anal canal, and anus). The data were fitted to log-linear age-period-cohort models. For each of the sub-sites, the age period-cohort patterns for males and females differed. Within each sex, sub-site groupings with common patterns were indicated. Among males, the age-period-cohort patterns for the colon sub-sites were fairly similar; but the pattern for the rectum differed markedly from that for the colon sub-sites. There were secondary differences among the colon sub-sites that pointed to a secondary distinction between the right and the left colons. Among females, the age-period-cohort patterns for the left colon sub-sites and the rectum were fairly similar. The pattern for the transverse colon differed moderately from that of the left colon, and differed substantially from that of the rectum and the ascending colon. The ascending colon differed markedly from each of the other sub-sites. It is possible that these differences in age-period-cohort patterns reflect etiologic distinctions among sub-site groupings and between the sexes. PMID- 8473050 TI - Time trends in cancer mortality in Estonia, 1965-1989. AB - Mortality rates for cancer of all sites combined and for 12 selected sites or site groups in Estonia from 1965 to 1989 were studied to assess overall progress in controlling cancer. Between 1965-1969 and 1985-1989, age-standardized mortality (world population) increased by 12.0% among males and decreased by 5.1% among females. The changes in mortality for the age-groups 20-44, 45-64, and 65 and over were -0.3%, 23.5% and 5.8% among males and 0.9%, -7.0% and -4.4% among females, respectively. In males, the most marked rise in mortality occurred for cancers of the oral cavity and pharynx, intestine and larynx. In females, the most rapid increase was observed for cancers of the lung, oral cavity and pharynx and breast. The decline in stomach cancer and cervical cancer mortality reflects worldwide trends. However, the noticeable increase in mortality rates for most of the sites indicates a need for strong preventive measures, particularly anti smoking campaigns. In general, the time trends in mortality from all cancers combined demonstrate that in Estonia, over the last 25 years, no progress against cancer has been achieved. PMID- 8473051 TI - Interleukin 7 enhances the proliferation and effector function of tumor infiltrating lymphocytes from renal-cell carcinoma. AB - Previous studies have documented the effects of IL2 on the growth and effector function of tumor-infiltrating lymphocytes (TIL) in cancer patients. Since IL7 is known to induce T- and NK-cell responses in the peripheral blood, we examined the immuno-enhancing effects of IL7 on TIL derived from human renal-cell carcinoma (RCC). Whereas IL2 induced the growth of freshly isolated TIL in vitro, IL7 was ineffective alone and failed to increase the total number of cells proliferating to IL2. However, IL7 did provide a proliferative signal to TIL that were initially expanded in culture with either IL2 or IL2/IL7 for 2 weeks. IL7 also induced the proliferation of CD4+ and CD8+ TIL lines that have specificity for RCC. The proliferative response induced by IL7 was independent of IL2, since anti IL2 antibodies did not block IL7-induced proliferation of TIL. IL7 did cooperate with anti-CD3 stimulation for the induction of proliferation; however, the magnitude of this interaction was variable and the response usually additive. In addition, IL7 synergized with anti-CD3 to induce the secretion of IFN gamma from short-term-cultured TIL and from a TIL line. Although IL7 did not promote the development of a tumor-specific T-cell response from IL2-expanded TIL, IL7 enhanced lymphokine-activated killer (LAK) activity from some short-term-cultured TIL. These results illustrate that IL7 can potentiate the growth and production of IFN gamma from RCC-reactive TIL and, to a lesser extent, enhance IL2-induced LAK activity of TIL. PMID- 8473052 TI - Shedding of GD2 ganglioside in patients with retinoblastoma. AB - Retinoblastoma is a rare tumor of the young child with an intraocular localization that leads to certain problems of diagnosis. With the aim of defining a biochemical marker--which is still lacking for this disease--the gangliosides of a pool of fresh retinoblastoma tumors were analyzed. The ganglioside pattern was shown to have GM3, GM2, GM1, GD3, GD2, GD1b and GT1b as the major components. The occurrence of a high concentration of GD2 in the tumors led us to investigate the possibility of changes in the level of GD2 in the sera of retinoblastoma patients, using quantitative immunostaining with GD2-specific mouse monoclonal antibodies (MAbs). In 9 out of 10 tumor-bearing patients, the serum level of GD2 ganglioside was significantly higher than the average value found in normal individuals. A 2-year follow-up of patients showed that successful treatment resulted in a rapid decrease in the serum level of GD2 down to the normal range, from which a subsequent elevation was seen only in relapsing patients. Although the clinical study needs further development, the results obtained to date suggest that GD2 is shed in the serum of tumor-bearing patients and that the level of GD2 could be a potential serum marker of human retinoblastoma. PMID- 8473053 TI - Involvement of p53 gene mutations in human endometrial carcinomas. AB - Mutations in the p53 gene are associated with a wide variety of human malignancies. Point mutation in one allele and loss of the remaining one generally lead to inactivation of p53 protein. A high frequency of allelic losses corresponding to the 17p13.3 region that contained the p53 gene sequence was also noted in human endometrial carcinoma. Thus, in order to confirm involvement of the p53 gene in endometrial carcinogenesis, we searched for nucleotide sequence change in this gene in 42 endometrial carcinomas that had been subjected to previous LOH analyses. Using the polymerase-chain-reaction-single-strand conformation polymorphism (PCR-SSCP) method, we detected p53 gene mutations in 4 specimens. Two adenocarcinomas with allelic loss on 17p contained a mutant p53 gene in the allele that was retained. One specimen with a p53 gene mutation contained a 17q deletion but was uninformative for LOH on 17p. p53 gene mutation was also noted in the remaining stage-I carcinoma, though the 17p deletion was not detected in the previous LOH examination. However, 5 specimens with the LOH on 17p retained the wild-type p53 gene. In the remaining 33 specimens, both alleles of p53 gene seemed to be normal. The mutations observed in 2 specimens (cases 10 and 24), involving C-to-T and T-to-G substitutions, were located in a highly conserved region. However, the mutations identified in the remaining 2 cases (29 and 35) were at regions positioned outside conserved stretches. PMID- 8473054 TI - Granulocyte-macrophage colony-stimulating factor induces human melanoma-cell migration. AB - Tumor metastasis is the primary cause of death for cancer patients. The metastatic cascade requires successful tumor cell invasion into and through vascular and parenchymal barriers. We have shown that autocrine motility factor (AMF, autotaxin) and the insulin-like growth factors (IGFs) induce tumor-cell migration. Since granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to prime neutrophils for chemotaxis, we have therefore studied the influence of GM-CSF upon tumor cells and report that GM-CSF stimulates migration of these cells in a dose-dependent fashion. The ED50 for A2058 human melanoma cell line chemotaxis to GM-CSF is approx. 60 pM. The motile response to GM-CSF was additive to that of IGF-I and AMF, both of which are potent attractants for tumor cells. Pre-treatment of cells for 2 hr with non-toxic concentrations of pertussis toxin (PT) or amiloride resulted in a 50% inhibition of chemotaxis to GM-CSF. Therefore, GM-CSF, through PT- and amiloride-sensitive signal pathways, is a potent attractant for melanoma cells, the response to which is additive to that of other attractants. The presence of the GM-CSF receptor in A2058 melanoma cells was indicated by Northern-blot analysis which identified message transcripts of 2.1 and 3.0 kb. These data emphasize the versatility of the melanoma cell migration response to an array of cytokines, including GM-CSF. PMID- 8473055 TI - Role of protein kinase C and cytokines on the function and production of cytolytic granules in alpha CD3-activated killer-cell-mediated killing of tumor cells. AB - The effects of PMA and staurosporine (PKC depletor/antagonist) and IL-2/IL4 were used to determine the role of PKC and cytokine on alpha CD3-induced activated killer cells (CD3-AK). The present study examines their effects on the production of BLT-esterase and on the effector function of CD3-AK cells as well as the cytolytic granules. The production of BLT-esterase generally correlated with the cytolytic activity of CD3-AK cells and was reduced by PKC depletor/inhibitor but increased by IL-4. In studying the effector function of CD3-AK cells, we found that adding PMA or SSP at the effector phase inhibited the PKC-dependent slow lysis. PMA, but not SSP, also reduced fast lysis, which was shown to be a PKC independent event. Additional experiments were performed to determine the effect of PKC on the lytic granules and to ascertain whether PMA has other effects on the effector-to-target relationship unrelated to PKC. It was found that neither PMA nor SSP affects the function of cytolytic granules, as measured by hemolytic assay against anucleated target (SRBC). These findings indicate that PKC has no direct effect on the granules. During testing against the nucleated tumor target through a novel approach using non-cytolytic surrogate killers, the lytic activity of the granules was inhibited by PMA, suggesting that exocytosis or delivery of granules to nucleated target cells may require mobilization of intracellular Ca2+ in the killer cells, and this process is inhibited by PMA. Our findings indicate that PKC and cytokines regulate the production but not the lytic activity of cytolytic granules. Nonetheless, delivery of cytolytic granules from killer cells to the nucleated tumor target appears to be a Ca(2+)-dependent event unrelated to PKC. PMID- 8473056 TI - Thrombin stimulates melanoma tumor-cell binding to endothelial cells and subendothelial matrix. AB - Thrombin has been shown to activate tumor-cell adhesion to platelets, fibronectin and von Willebrand factor 2- to 3-fold in vitro, and enhance metastasis 10- to 156-fold in vivo. We therefore elected to determine whether thrombin binds to tumor cells and whether thrombin-treated tumor cells enhance their adhesion to endothelial cells, the first barrier to tumor invasion and metastasis. Thrombin treated human and hamster melanoma cells (SK-Mel-28 and HM-29) enhanced their adhesion to bovine aortic endothelial cells 2.1- to 2.3-fold, respectively. Similar results were obtained with bovine capillary endothelial cells. Thrombin activation of tumor cells was rapid, reaching its peak 15 min after thrombin activation; and transient, declining to baseline levels by 60 min. 125I-thrombin bound to both SK-Mel-28 and HM-29 cells in a saturation-dependent manner, was inhibitable by unlabelled thrombin, and could be 90% washed away with buffer following 30 min of incubation. Electron microscopy of tumor cells bound to fibronectin-coated millipore filters revealed adhesion of naive as well as thrombin-treated tumor cells to endothelial cells and subendothelial matrix between endothelial cells. Neither mode of adhesion was preferentially enhanced by thrombin-treated tumor cells. Both naive and thrombin-treated SK-Mel-28 cells had the adhesive ligand integrin receptors: alpha 3 beta l (fibronectin, laminin, collagen); alpha 5 beta l (fibronectin); alpha v beta x (vitronectin). Receptors for the beta 2 integrin family (LFA-I and Mac-I) were not found, nor were receptors of the beta 3 integrin family, GPIIIa. The receptor ligands fibronectin and vitronectin were present. None of the above receptors or ligands increased their density or appeared de novo after thrombin stimulation. Thus, 2 melanoma cell lines have thrombin receptors which, when occupied, lead to enhanced adhesion of tumor cells to endothelium and subendothelial matrix. PMID- 8473057 TI - Ultrastructural evidence of the mechanisms responsible for interleukin-4 activated rejection of a spontaneous murine adenocarcinoma. AB - The ultrastructural pattern of the anti-tumor response elicited by interleukin-4 (IL-4) was investigated by using a spontaneous mammary adenocarcinoma (TS/A) unable to elicit protective immunity in syngeneic BALB/c mice as suggested by a variety of preimmunization-challenge experiments. A subcutaneous lethal challenge of TS/A tumor cells was inhibited in a significant number of BALB/c mice receiving recombinant murine IL-4 injected daily for 10 days around the tumor draining lymph node. Tumor rejection was mainly the result of direct membrane and cytoplasmic damage to tumor cells by eosinophils, neutrophils and macrophages that deeply penetrated the proliferating tumor mass. Lymphocytes and fibroblasts participated in the reaction by interacting with tumor cells, granulocytes and each other. The most frequent cell interactions in the peri- and intra-tumoral areas and in the tumor-draining lymph nodes are illustrated. The efficiency with which the IL-4-activated reaction leads to tumor inhibition and induction of a T lymphocyte-dependent tumor-specific immune memory appears to depend on interactions between distinct leukocytes. PMID- 8473058 TI - The treatment of addiction in group psychotherapy. AB - This article gives specific reasons and evidence why group psychotherapy is the treatment of choice for addictions. Utilizing object relations theory and the self-psychology of Kohut, the authors present a model of group psychotherapy that combines these perspectives with those of Yalom's interactional group psychotherapy. Agreeing with Kohut and other object relation theorists, the authors view addiction as a condition that is the result of a person's misguided attempts at self-repair because of deficits in psychic structure. Vulnerability of self is the consequence of developmental failures and deprivation. Substance abuse only exacerbates this condition leading to exaggerated difficulty in regulation of affect, self-care, and characterological pathology. Abstinence is usually required as the first step in arresting this process and establishing a treatment regimen that will allow the vulnerabilities of the self to be altered and restored. This article suggests that this recovery and treatment process is best accomplished in a group therapy setting that is conducted within the guidelines of the principles of object relations theory and a modified version of Yalom's interactional group therapy format. PMID- 8473059 TI - Groups for the chronic mental patient and the legacy of failure. AB - Group treatment of the chronically mentally ill has often been a fruitless and exasperating experience. The intense emotional responses of group leaders in working with this chronic population reinforces a spiral of repetitive failures. An attempt to intervene in this chronic spiral will be presented by the author's experience in leading a training group of mental health workers who, in turn, lead groups of chronic patients. In particular, the effects of projective identification on various holding environments will be examined by using the methodology of object relations. Understanding and utilizing countertransference responses of the training leader illuminate the unconscious aims of chronic patients to perpetuate their internal and interpersonal lives by their effect on the group leaders who work with them and on each other. This understanding can lead to interventions that have more constructive outcomes. PMID- 8473060 TI - "Telling one's story" in an incest survivors group. AB - This article discusses the technical considerations that contribute to making "telling one's story" in an incest survivors group a ritual of active mastery leading to psychological growth. Survivors approach the task of sharing memories with a variety of wishes and fears that can emerge as powerful group transference paradigms. These paradigms, while they vividly illuminate the survivor's past and present interpersonal expectations, can threaten to derail the telling experience. Actively interpreted, however, the group transference aspects of the telling experience can yield valuable insights that become the focus for the remainder of the survivor's group treatment. This article details the process of preparing the individual survivor and the group for the process of telling (and listening) and the subsequent task of working through the insights derived from the telling experience. Two case examples demonstrate these techniques. PMID- 8473061 TI - A group psychotherapy approach to postpartum depression. AB - In this article, the current knowledge of postpartum depression is reviewed, leading to an understanding of this form of depression as an expression of psychosocial factors compounded by the biological changes of the puerperium. A rationale for treating women in the context of the postpartum period is described. A novel approach to treatment is presented. The treatment uses the medium of group psychotherapy to administer interventions. The interventions are introduced in three phases across six months in weekly group sessions. The systematic intervention program focuses on decreasing four symptoms common to postpartum depression: depressed feelings, anxiety, distress, and low self esteem. Spouses are involved in the treatment plan from the onset, participating in assessment sessions and in a couples group. PMID- 8473062 TI - How to deal with moral issues in group therapy without being judgmental. AB - The author discusses the pervasive difficulty psychotherapists seem to have in discussing patient morality, relating it to the fear of imposing (and feeling) shame and guilt. A way of nonjudgmentally discussing moral values with patients is presented, which places emphasis not on moral abrogations, but rather on the "virtues" of altruism, responsibility, justice, egalitarianism, and honesty. Drawing on empirical studies of prosocial behavior, the author gives a rationale for how these virtues may, whether the therapist is conscious of it or not, be inherently promoted through the group therapy process. Ways are suggested by which the therapist can help the group deal with thorny moral issues and confront the morally confused patient without causing shame. PMID- 8473063 TI - Developing object constancy in group psychotherapy. AB - This article describes a therapeutic approach that fosters the development of object constancy in group psychotherapy. By managing group boundaries, instilling an analytic attitude of self-reflective curiosity, and fostering shared group experiences, the therapist helps to create an environment in which individuals can develop a constant sense of themselves and relate to others as separate and distinct persons. PMID- 8473064 TI - The use of a group meal in the brief group therapy of bulimia nervosa. AB - The group meal is a technique that can be easily incorporated into traditional forms of short-term group therapy for bulimia nervosa. It is a modification of the exposure and response-prevention model that has been used in the treatment of this population. Patients plan and eat a meal together with the group therapist during one of the group therapy sessions. Over the course of the meal, patients discuss thoughts and feelings as they experience them, allowing for greater depth of therapeutic work than when simply recalling events that occurred between sessions. A case example is described to illustrate several of the important themes that emerge, including reactions to feeling full, family meals, and the relationship between overeating and feelings about the self. PMID- 8473065 TI - Writing for publication: overcoming common obstacles. AB - This article presents the results of a survey of recent authors in the International Journal of Group Psychotherapy who were asked to identify (a) the three most difficult obstacles they encountered when publishing their first article, (b) three types of resources that were most helpful when preparing their manuscript for publication, and (c) advice they would offer to authors who are planning their first paper for submission to a mental health journal. Common problems in manuscripts submitted for editorial review are also highlighted, based on an analysis of 150 letters mailed to authors whose papers were rejected or accepted pending revision. The goal of the present article is to provide guidelines for how to publish successfully. PMID- 8473066 TI - Microlymphatics of human skin. AB - Microlymphatics of human skin form two superposed networks. The superficial one located at the level of dermal papillae may be visualized by fluorescence microlymphography. Microlymphatics fill from a subepidermal depot of minute amounts of FITC-dextran 150,000. In primary lymphedema with late onset the depicted network with vessels of normal size is significantly larger than in healthy controls, whereas in congenital lymphedema (Milroy's disease) microlymphatics are aplastic or ectatic (diameter > 90 microns). Lymphatic microangiopathy with obliterations of microvessels develops in chronic venous insufficiency, in lipedema (preliminary results) and after recurrent erysipelata. In healthy controls microlymphatics are permeable to FITC-dextran 40,000 and impermeable to the larger molecule 150,000. Preserved fragments of the network in chronic venous insufficiency exhibit increased permeability to FITC-dextran 150,000. After visualization of the vessels by the fluorescent dye microlymphatic pressure may be measured by the servo-nulling technique. First results indicate that microlymphatic hypertension contributes to edema formation in patients with primary lymphedema. PMID- 8473067 TI - Erythrocyte-leukocyte interactions in the vascular bed of isolated perfused rat lungs. AB - An earlier study of perfused rat lungs showed that leukocytes, given as bolus injections, seemed to become more or less permanently trapped in the pulmonary microvascular bed under erythrocyte-free perfusion. The aim of the present study was, therefore, to investigate the rheologic effects of erythrocytes on the leukocyte microcirculation of perfused rat lungs. Leukocyte and erythrocyte suspensions were given as bolus injections during cell-free, constant pressure perfusion of ventilated rat lungs. Leukocyte numbers were counted in samples of the venous effluent and flow resistance changes were computed from registrations of flow rate, arterial and venous pressures. The preparations showed a continuous efflux of leukocytes which had been trapped in the pulmonary microcirculation before the perfusion was started. A bolus infusion of erythrocytes (3 ml, hematocrit: 30%) caused a transient flow resistance increase during the passage of the erythrocyte bolus through the vascular bed. This initial peak was accompanied by an increased venous efflux of leukocytes and followed by a lower second peak, attributed to a redistribution of trapped leukocytes in the capillary bed. Infusions of mixed cell suspensions (20-30 x 10(6) leukocytes in 30% hematocrit) caused a transient resistance increase similar to that caused by erythrocytes and a sustained resistance increase, less persistent than that caused by leukocytes. The present data suggest that the infusion of erythrocytes caused a re-distribution and an increased efflux of leukocytes, pooled in the pulmonary microcirculation. The rheological effects of erythrocytes could, hypothetically, result from mechanical interactions with the leukocytes in the pulmonary microvessels. PMID- 8473068 TI - Fine structure of capillaries in ischaemic and non ischaemic rat striated muscle. Effect of torbafylline. AB - Capillary ultrastructure was studied in ischaemic and contralateral extensor digitorum longus (EDL) muscle, in the diaphragm and left ventricular papillary muscle of rats with unilateral ligation of the common iliac artery (L), in ischaemic stimulated muscles (SL), and in ischaemic stimulated muscles of animals treated with a new xanthine derivative, torbafylline (SL&T). Muscles were stimulated at 10Hz via implanted electrodes 7 times/day for 2 weeks. Torbafylline or water was given by gavage morning and evening. Nominal evaluation of capillary ultrastructure revealed endothelial swelling in 52.7 +/- 8.7% (mean +/- SEM) capillaries in ischaemic muscles, 35.2 +/- 5.6% in contralateral muscles and about 30% in the diaphragm and papillary muscle. Stimulation of ischaemic muscles increased this proportion to 62.6 +/- 6.2% (not significant vs. L), 57.8 +/- 9.5% (p < 0.05 vs. L), 62.6 +/- 6.3 (p < 0.05 vs. L) and 43.7 +/- 4.2% (p < 0.05 vs. L) in ischaemic and contralateral EDL, diaphragm and papillary muscle, respectively. Administration of torbafylline reduced the proportion of swollen capillaries to 37.8 +/- 6.1.45% (p < 0.02 vs. SL) in ischaemic muscles, and to 26.2 +/- 2.1% (p < 0.001) in papillary muscle, with a smaller effect in the contralateral EDL and the diaphragm. Stereological analysis showed that stimulation led to a marked increase in capillary size vs. contralateral muscles. A similar lumen volume density across all groups (Vv = 0.36-0.39), vs. control Vv = 0.47, reflected structural heterogeneity within the capillary population of EDL. For most components this intra- animal variation obscured drug treatment effects, the exception being Vv(nucleus) which was least in SL&T. Activity in ischaemic muscles can thus result in widespread capillary endothelial damage in muscles, and attenuation of this swelling by torbafylline may explain the beneficial effect of this drug on capillary perfusion and performance. PMID- 8473069 TI - Spatial relationship between leukocyte accumulation and microvascular injury during reperfusion following hepatic ischemia. AB - In order to further elucidate the possible contribution of leukocytes to microvascular injury during reperfusion following total hepatic ischemia, we studied the spatial relationship between areas of white cell accumulation and areas of microvascular damage in the rat liver in vivo. No-flow hepatic ischemia was produced for 90 min in vivo and during the ensuing reperfusion phase (I/R) leukocyte accumulation, absolute number of perfused sinusoids per unit area, and red blood cell velocity were quantitated using in vivo epi-fluorescence video microscopy. The total number of stationary leukocytes in the liver during reperfusion was found to be significantly elevated following ischemia compared to time-matched sham-operated controls. In addition, by 2 hr of reperfusion, approximately 80% of the leukocytes in the I/R group were extravascular compared to only about 50% in the controls. When leukocyte accumulation and microhemodynamics were expressed on the basis of whole liver, the increased accumulation of leukocytes was associated with decreased microvascular perfusion as indicated by decreased number of sinusoids perfused and decreased red blood cell velocity. However, when the data were analyzed on the basis of .05mm2 microscopic fields on the surface of the liver, there was no difference in leukocyte accumulation in areas with sinusoidal blood flow compared to areas that were devoid of perfused sinusoids. Moreover, in a correlation analysis of number of adherent leukocytes/microscopic field vs red blood cell velocity in perfused sinusoids in that field, only a very small negative correlation between leukocytes/field and red blood cell velocity was found (r = -.23, p < .05). These results demonstrate that at the whole organ level leukocyte accumulation appears to correlate well with microvascular damage; however, this increase in whole liver accumulation of leukocytes does not necessarily reflect accumulation at sites of overt microvascular damage. Thus, leukocyte-independent factors are likely to be of considerable quantitative importance in microvascular injury during reperfusion following hepatic ischemia. PMID- 8473070 TI - Involvement of 5-lipoxygenase products in cigarette smoke-induced leukocyte/endothelium interaction in hamsters. AB - Although cigarette smoke (CS) has been identified as an independent risk factor for atherogenesis and sudden cardiac death, the underlying pathomechanism has not been clarified. A common factor of both atherogenesis and ischemia/reperfusion damage associated with myocardial infarction is the adhesion of circulating leukocytes to the vascular endothelium. Searching for the mechanism by which CS exerts its deleterious effects on the cardiovascular system, we used a dorsal skinfold chamber model in hamsters for intravital microscopy to examine the effect of CS on the interaction of fluorescently stained leukocytes with the microvascular endothelium in striated muscle. Exposure of awake animals (n = 7) for 5 minutes to the mainstream smoke of one cigarette (2R1 research cigarette) elicited rolling and subsequent adhesion of circulating leukocytes to the endothelium of both arterioles and postcapillary venules with a maximum 30 minutes after CS-exposure. In order to test a putative mediator role of the chemotactic and adhesion-promoting leukotrienes in this event, we pretreated another group of 7 animals with MK-886, a potent and specific inhibitor of leukotriene biosynthesis (20 mumol/kg body weight, iv, 30 minutes prior to CS exposure). While no inhibitory effect was seen on CS-induced leukocyte rolling along the microvascular endothelium. MK-886 pretreatment significantly attenuated leukocyte adhesion to arterioles (5.2 +/- 13.7 cells/mm2 vs. 54.1 +/- 54.8 in control animals. P < 0.01) and venules (37.0 +/- 33.6 cells/mm2 vs. 161.6 +/- 91.1 in control animals, P < 0.01), 30 minutes after CS exposure, suggesting a key mediator role of leukotrienes in this event. We propose that the stimulation of leukocyte/endothelium interaction by CS may provide the pathophysiologic basis for--or at least contribute to--its deleterious effects on cardiovascular mortality and morbidity. The identification of the mediator role of leukotrienes in this event may open the way to novel pharmacologic and dietary approaches for the prophylaxis of CS-induced cardiovascular pathology. PMID- 8473071 TI - Evidence of flowmotion induced changes in local tissue oxygenation. AB - The effect of cyclic blood flow velocity on local tissue oxygenation was studied by means of a mathematical simulation in the situation where red blood cells (RBC) act as discrete oxygen sources. Cyclic time varying fluctuations of capillary blood (flowmotion) are due to arteriolar vasomotion. This effect was introduced into the model as an oscillating RBC velocity with equal periods of high and low velocity regulated by a square wave function. Changes in RBC velocity coupled with a constant time-average capillary hematocrit lead to periods of high and low flux. Input parameters were flowmotion frequency and amplitude, capillary hematocrit, and mean RBC velocity. All results were related to baseline states where the velocity and hematocrit are steady. Our principle finding is that flowmotion alters the tissue oxygenation, whereby: 1) high amplitudes of flowmotion cause a modest increase in axial delivery of oxygen but with a decreased average tissue pO2; 2) decreasing flowmotion frequencies lead to increased radial penetration of oxygen; 3) the lower frequencies of flowmotion cause an increase in the volume of tissue that achieves at least a pO2 level of 5 mmHg. Isovolemic hemodilution was simulated and found to substantially increase the volume of oxygenated tissue as a function of flowmotion. These findings indicate that pO2 transients caused by flowmotion oxygenate tissue domains which under steady-state conditions would remain anoxic. PMID- 8473072 TI - Biological zero in laser Doppler measurements in normal, ischaemic and inflamed human skin. AB - The Biological Zero (BZ) signal in laser Doppler flowmetry was recorded during temporary occlusion of the arterial circulation to the limb by a blood pressure cuff inflated suprasystolically for 2 min. The non-thermoregulatory skin at the ankle was compared with the thermoregulatory skin over the toe pad in patients with lower limb arterial obstructive disease, elderly controls without arterial disease and young healthy adults under cool (15-17 degrees C) and warm (25-27 degrees C) ambient conditions. The absolute BZ values did not differ significantly within the three groups at the two room temperatures. However the resting laser Doppler flowmetry signal (LDflux) was consistently higher under warm than cold room temperatures: these differences were much greater at the toe than at the ankle. Accordingly, the relative size of BZ, expressed as a percentage of the resting LDflux, was least over the toe in a warm room (5-10%) and greatest over the malleolus (59-83%) in the cold room. The changes during the evolution of a positive tuberculin skin reaction were followed as a model of chronic inflammation in man. The resting LDflux rose 10 fold (from 0.3 to 3.4V) while the change in the BZ was minor (0.16-0.2V). Thus the rise in LDflux in a fully developed tuberculin reaction was approximately 30X greater than that for the corresponding BZ. Concurrent measurements of the alternative output from the laser Doppler flowmeter (CMBC) showed in a similar pattern. Since the BZ signal can be a substantial proportion of the resting LDflux measurement, we support the recommendation that the BZ should be measured wherever possible and practicable, for subtraction from the observed LDflux to assess the true flow: 'raw' LDflux measurements should be interpreted with extreme caution, particularly at relatively low resting LDflux levels. PMID- 8473073 TI - Evidence for skin microvascular compartmentalization by laser-Doppler and photoplethysmographic techniques. AB - Indices of perfusion were obtained using commercial laser-Doppler instruments with differing wavelengths on metatarsal skin of sheep (which is abundant with AVAs) and compared with quantitative measurements of AVA and capillary blood flow using microspheres; an infra-red photoplethysmograph was also compared. The data provide physiological evidence that laser-Doppler instruments of longer wavelength sense to a greater depth, and our photoplethysmograph behaves similarly to a "near-infra-red" laser. Thus, we suggest that near-infra-red light, either laser-Doppler or photoplethysmograph, should be used to measure a parameter most representative of total local blood flow, and light of a very much shorter wavelength, probably green light, would allow more confidence in estimates of true capillary perfusion. Because the commonly used visible red light can, but does not necessarily detect deep AVA perfusion, the influence depending upon the magnitude of the AVA perfusion, measurements by an instrument based on such red light is difficult to define. PMID- 8473074 TI - The "learning curve" in the performance of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy was successfully performed on 23 of the first 28 patients in whom this was attempted (82.1%). After the first ten cases, the success rate increased to 94.4%. There was only one major complication which prolonged hospital stay but did not require re-operation. Operative time decreased markedly from a mean of 160 minutes for the first ten cases to 61 minutes for the remainder. This increase in operative speed was not accompanied by an increase in complications, in spite of a liberalization of patient selection criteria. It is clear that a steep "learning curve" exists for this procedure and must be recognized and appreciated if laparoscopic cholecystectomy is to become a safe and efficient procedure. PMID- 8473075 TI - Multivariate study of prognostic factors for differentiated thyroid carcinoma: the significance of histologic subtype. AB - We re-examined 239 patients with differentiated thyroid carcinoma (222 with papillary carcinoma and 17 with follicular carcinoma) especially for the clinico pathologic entity of poorly differentiated carcinoma, and made univariate and multivariate analyses of the results to evaluate whether it would be of value in estimating the prognosis in thyroid cancer patients. In the univariate study, no significant difference was found in either survival and disease-free survival between papillary and follicular carcinomas, but between well differentiated and poorly differentiated carcinomas. In the multivariate study, however, the presence of poorly differentiated carcinoma did not appear to be an unfavorable prognostic factor. The sex, tumor size, and presence of distant metastases or grossly malignant residue in the neck after operation were, on the other hand, confirmed by the analyses to be important prognostic factors. We concluded that histologic subclassification may be less useful in estimating the prognosis in patients with differentiated thyroid carcinoma than other factors such as sex and the extent of the tumor. PMID- 8473076 TI - Analysis of hepatic recurrence of colorectal cancer after resection of hepatic metastases. AB - Forty patients with history of resected hepatic metastases of colorectal cancer were examined for pattern of recurrence. The 5-year survival rate was 41.3% for 40 patients. Recurrences of the malignancy were seen in 25 of the patients, with hepatic recurrence in 42.5% of them. The hepatic recurrence rate did not correlate with the lobar distribution of metastases or surgical methods. The pathological margins of less than 1 cm, 3 or more liver metastatic lesions, and the metastatic lesions of greater than 5 cm were at increased risk of hepatic recurrence. The recurrence rate was high, or 56% for aneuploid tumors, while it was 18.5% for diploid tumors. PMID- 8473077 TI - Increased leukocyte adhesiveness/aggregation and tissue leukostasis following surgical trauma. AB - The purpose of the present study was to document the increased leukocyte adhesiveness/aggregation (LAA) and tissue leukostasis that follow surgical trauma. We found that following major abdominal surgery, the percentage of aggregated leukocytes in the peripheral blood increased from 8.6 +/- 7 to 21.7 +/ 11.5 (p < 0.001), while the respective values for patients undergoing minor surgery were 3.7 +/- 2.4 and 19.7 +/- 7.6% (p < 0.001). The state of LAA was also determined in eight dogs after partial collectomy and four controls. A clear increment in the degree of tissue leukostasis (especially in the spleen, liver and lungs) was noted in the operated as compared to the control animals. In addition, a significant correlation was found between the state of LAA, determined in the venous (p = 0.0004) and arterial (p = 0.002) blood of these animals and the degree of tissue leukostasis. We conclude that a state of increased LAA in the peripheral blood is induced by surgical trauma and that this increased LAA correlates with tissue leukostasis. PMID- 8473078 TI - Traffic accident induced thoracic outlet syndrome: decompression without rib resection, correction of associated recurrent thoracic aneurysm. AB - Traffic accident injuries accounted for the sum of 72 billion in the United States last year. These injuries included Thoracic Outlet Syndrome and its associated Thoracic Aortic Aneurysms. Typically, the injured person has stopped for a red traffic light when another vehicle of higher speed and weight hits the stopped vehicle from behind. The force exerted hyperextends the neck and stretches the scalenus muscles. The muscles stretch, bleed, hypertrophy, and shorten. This process further narrows the already crowded triangular tunnel through which the neurovascular bundle passes. Sixty-five severely symptomatic Thoracic Outlet patients were operated on no sooner than two months after the accident to allow the non-surgical measures to take effect. The median age for these patients was 33.8 years. The female to male preponderance was 40/25. All patients had MRI of the cervical spine to rule out radiculopathy. MRI of the thorax was also requested when a Thoracic Aneurysm was suspected. Nerve conduction tests of the upper extremities were also taken to support the diagnosis. The most valuable clinical test was Elevated Arm Stress Exercising which was positive in all cases. At operation, the Brachial Plexus was compressed mostly by the hypertrophied, adherent, and fibrous scalenus medius from behind. The approach was anterior and supraclavicular in all cases including the recurrent one. Both scalenus medius and anticus were largely resected to enlarge the Thoracic Outlet triangular tunnel. The first rib was not resected in any of these patients, but all costo-cervical ligaments and bands and/or cervical ribs were resected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473079 TI - Iatrogenic perforations of the esophagus. AB - The authors herein report their personal experience in the management of 21 patients with iatrogenic perforation of the esophagus, collected in a fifteen year period. The etiology was more commonly a hiatal surgical procedure (28.6%), following diagnostic endoscopy (19%), endoscopic dilatation for achalasia (19%) and foreign body (19%). Consequently, 47.6% of the lesions were located in the abdominal, 28.6% in the thoracic and 23.8% in the cervical esophagus. Treatment was set up at surgery in 28.6%, within 6 hours in 47.6% and within 48 hours in 9.6%. Conservative medical management was successfully carried out in three cases (14.2%). As a result of their policy of "tailored" treatment on single lesion characteristics (size and location, underlying esophageal diseases, early or delayed diagnosis) they report an overall mortality rate of 28.6%, the prognosis being worse in thoracic (50%) than in abdominal perforations (30%). Based on this series and on a literature review the authors suggest that the best management should be "tailored" to single patients characteristics. Early diagnosis and treatment are the most important prognostic factors. PMID- 8473080 TI - Diagnosis and management of heterotopic pancreas. AB - Fifteen patients with 16 histologically verified heterotopic pancreas lesions were encountered at our department during a period of 22 years. The incidence was 0.25% of the findings of all abdominal operations during the same period. Heterotopic pancreas caused symptoms in 5 patients. All the remaining 10 patients were asymptomatic, whose lesions were found coincidentally at the time of surgery for other abdominal diseases. Heterotopic pancreas developed most frequently in the jejunum (46.7%). Preoperatively, only 2 lesions of the stomach in 2 patients were suspected to be heterotopic pancreas. At the time of operation, 10 of 16 lesions were diagnosed correctly on the basis of the macroscopic features. Malignant degeneration was seen in the duodenal and jejunal heterotopic pancreas. The former lesion was successfully resected by pancreatoduodenectomy. There were no deaths related to heterotopic pancreas or to the operations performed. Resection of the tissue-bearing area is advisable when the condition is encountered coincidentally at operation, and surgical exploration should be done for all symptomatic patients, particularly in the absence of histological diagnosis. PMID- 8473082 TI - Videoendoscopic thoracic surgery. AB - Personal experience of 42 videothoracoscopic operations is reported. From September 91 to May 92 we performed 10 major lung resections (1 pneumonectomy, 8 lobectomies, 1 segmentectomy) 9 wedge lung resections, 4 excisions of pulmonary bullae, 12 pleurectomies with or without apicectomy, 6 excisions of mediastinal masses (3 thymomas, 2 mediastinal cysts, 1 thoracic disembryoma), 1 removal of esophageal leiomyoma. No major complications occurred. Except for one patient submitted to bullectomy with pleurectomy who required a second thoracoscopy due to postoperative bleeding, all patients had excellent p.o. course. We describe technical details employed in different videothoracoscopic operations and discuss personal results and principles of videothoracoscopic approach. Different fields of videoendoscopic chest surgery are examined. Present data seem to advocate videothoracoscopic treatment for many thoracic diseases and also for major lung resections, due to its minimal trauma and little functional impairment. Nevertheless this still remains avant-garde surgery. Further improvement in endoscopic instrumentation is necessary and may lead to future extensions of videothoracoscopic surgical possibilities. PMID- 8473081 TI - The value of histological study by surface analysis of preserved and injected pancreatic grafts: a prospective controlled study in dogs. AB - To evaluate the effects of pancreas preservation and pancreatic duct obliteration on the endocrine pancreas, three groups of dogs were used: a control group (six) in which histologic analysis of normal pancreas was performed and two randomized groups (seven) from which the caudal pancreas was auto-transplanted, injected with fibrin glue and removed on the 28th day. In Group A, each graft was flushed out with Euro-Collins' solution and immediately transplanted. In Group B, each graft was preserved 24 hours in a preservation solution and transplanted. Islet surface ratios on the sections and mean islet surfaces were greater in the control group than in Group A (p = 0.011 and 0.023) and no different between control group and Group B (p = 0.334 and 0.099). This surface analysis study suggests that the mode of management of grafts in itself explains the alteration of endocrine pancreas and that obliteration of the pancreatic ducts has little influence on this alteration. PMID- 8473083 TI - Diagnostic and therapeutic strategies of pyogenic liver abscess. AB - The infectious routes and etiologies of 26 cases with pyogenic liver abscess were portal spread in one, hematogenous in three, biliary in 12, transarterial embolization (TAE) in three, posthepatectomy in one and cryptogenic in five cases. Portal and hematogenous cases tend to show solitary and cystic pattern on echogram, and the majority of the bacteria detected was Klebsiella. While most biliary cases show multiple and cystic with tumor pattern on echogram, and an unhomogeneous low density in CT feature, anaerobic bacteria and candida were isolated only from the biliary or TAE cases. Most cases could be cured completely by the various kinds of abscess drainage, but two TAE cases with PTAD (percutaneous transhepatic abscess drainage) and two biliary cases with PTBD (PT biliary drainage) and PTAD died due to a delay in establishing a diagnosis and to the severity of the condition. An early diagnosis followed by PTAD or PTBD were thought to be of prime importance. PMID- 8473084 TI - Caroli's disease: study of six cases, including one with epithelial dysplasia. AB - Six cases of Caroli's Disease are reviewed. Three of the patients had an associated form of the disease, one of which had a congenital hepatic fibrosis, another a cystic dilatation of extrahepatic bile duct and the last one suffered both the above mentioned associated anomalies. Three patients presented with the simple form which was initially described by Caroli. The distribution of the biliary lesions was a bilobar one in four cases and monolobar in two. One patient presented areas of biliary ectasia partially lined by dysplastic epithelium. Surgical treatment was used in four cases, a left hepatectomy being carried out in two of them and an internal biliary drainage by Roux-Y hepaticojejunostomy in the other two. This is a rare disease, frequently associated with congenital hepatic fibrosis, possibly pre-malignant and whose treatment of choice is hepatic resection. PMID- 8473085 TI - Thrombolytic therapy before reconstructive vascular procedures for acute or subacute graft occlusions. AB - The purpose of this study was to evaluate the efficacy of direct intra-arterial Urokinase infusions prior to anticipated adjunctive reconstructive vascular procedures in 16 patients with 24 acutely or subacutely occluded lower extremity grafts (22 femoropopliteal, 2 femorotibial). Complete thrombolysis was achieved angiographically in 18 (75%) of 24 graft occlusions. Neither age, gender, current smoking, diabetes mellitus, hypertension, nor coronary arterial disease were significantly associated with complete thrombolysis. The only significant factor related to complete thrombolysis was the duration of the occlusion prior to lytic treatment (p < 0.05). Adjunctive reconstructive procedures were performed for eleven of 18 cases in which complete thrombolysis was achieved. These included nine percutaneous transluminal balloon angioplasties (at eight distal and one proximal anastomotic stenoses) and two bypass operations (femoropopliteal). The remaining seven cases had no adjunctive procedure. These 18 cases were examined for patency rates during nine months of follow-up. Six (54%) of 11 cases with adjunctive reconstructive vascular procedures remained patent, while one (14%) of seven cases with no adjunctive procedure remained patent (p = 0.1). Six (25%) of 24 cases resulted in incomplete thrombolysis. Vascular procedures following these cases included two bypass operations, three amputations and one sympathectomy. This study suggests that complete thrombolysis of acutely occluded grafts might have minimized subsequent reconstructive procedures. Identification of correctable lesions and adjunctive reconstructive procedures performed following complete thrombolysis may be the important factors related to long-term patency. PMID- 8473086 TI - Intra-arterial streptokinase as adjuvant therapy for complicated Buerger's disease: early trials. AB - Selective low-dose intra-arterial streptokinase was used in 11 long standing, complicated cases of Buerger's disease of the lower limbs suffering from acute exacerbations or thrombotic episodes with resulting variable degrees of gangrene or pre-gangrene of toes or feet, often despite previous lumbar sympathectomy. They had no other possible therapeutic options but wait for major amputation. The overall success rate (with amputation avoided or altered) was 58.3% and bleeding complications occurred in 16.6% of the total limbs at risk included. Favorable factors influencing the therapeutic outcome of thrombolytic therapy were a shorter presentation time, previous sympathectomy and nicotine abstinence. Even with necessary precautions, the technique does not seem to be totally safe. However it can be rewarded in some properly selected cases. PMID- 8473087 TI - Myxoid chondrosarcoma of the abdominal aorta. AB - In this case report we present a 64 year old man who underwent resection of his infrarenal abdominal aortic aneurysm. Thrombus of unusual color, texture and consistency was noted within this aneurysm which upon histopathologic analysis had the characteristics of a myxoid chondrosarcoma. Primary myxoid chondrosarcoma of the abdominal aorta is very rare and to our knowledge this report represents the first recorded case. The clinical presentation of our patient was dominated by hypertension and severe lower extremity claudication associated with microembolization to the left fourth toe. PMID- 8473088 TI - Immunoprophylaxis in "septic risk" patients undergoing surgery for gastrointestinal cancer. Results of a randomized, multicenter clinical trial. AB - The results of a randomized, multicenter clinical trial of immunoprophylaxis of post-operative infections with intravenous Immunoglobulins (IVIG) (Sandoglobulin) in "septic-risk" patients undergoing surgery for gastrointestinal cancer are presented. "Septic-risk" patients were selected by an original multiparametric test based on delayed hypersensitivity skin testing and serum protein electrophoretic sub-fractions. This screening test had shown 76% positive predictivity in a previous validation assessment. In the present study, 159 "septic-risk" patients were selected prospectively from 369 patients undergoing colo-rectal (colon) and other kinds of gastrointestinal (non-colon) oncologic surgery: 80 "septic-risk" patients were included in the colon and 79 in the non colon group. Immunoprophylaxis with IVIG (15 g on the day prior to operation, on the 1st and 5th postoperative days) was randomly associated with antibiotic prophylaxis (cefoxitin: 2 g one hour prior to, followed by 2 g at the end of operation plus 2 g every six hours for 24 hours) in colon surgery while the prophylactic schedule in non-colon surgery was only based on random administration of IVIG, at the same dosage as in the colon group. There was a clear-cut reduction of post-operative infections both in colon and non-colon "septic-risk" patients who had IVIG prophylaxis; in the colon group, 37 and 21 infections (P < 0.004) in antibiotic (A) versus IVIG plus antibiotic (IVIG + A) subset, respectively; in the non-colon group, 33 and 19 infections (P < 0.01) in control (C) versus (IVIG) subset, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473089 TI - Iatrogenic ocular complications in patients after jejunoileal bypass surgery. AB - We conducted complete eye examinations and retinal function tests on nine patients who had undergone jejunoileal bypass (JIB) surgery and subsequently had low serum vitamin A levels. All patients had manifested clinically demonstrable keratoconjunctival xerosis; in addition, two had abnormally high dark-adaptation final thresholds, and two had concomitant implicit prolongation in the electroretinogram. The age-matched control groups that consisted of 14 patients with various gastrointestinal disorders and four asymptomatic volunteers showed fewer or no ocular abnormalities. Our findings suggest that, even though patients who underwent JIB surgery may manifest keratoconjunctival xerosis and have low serum vitamin A levels for several months to years, retinal function will remain normal until the tissue stores of vitamin A are depleted. A long-term ophthalmologic follow-up of JIB patients, therefore, is recommended. PMID- 8473090 TI - Bilateral orchiectomy in the management of stage D-2 prostate cancer. AB - The records of 115 patients with stage D-2 prostate cancer treated with bilateral orchiectomy were reviewed to determine the effect of this procedure in previously untreated patients and in patients who had prior hormone therapy. Previously untreated patients survived 22.8 months while those who had prior hormone therapy survived 39.3 months (p < 0.001). Bilateral orchiectomy may be of additional clinical benefit in patients with advanced prostate cancer who have had prior hormone therapy. PMID- 8473091 TI - Experience in 4500 cases of laparoscopic sterilization. AB - Laparoscopic sterilization under local anaesthesia was found to be a safe and effective procedure and the most popular method of voluntary sterilization in rural India. The difficulties encountered included omental emphysema and prolapse, bleeding from the mesosalpynx, cervix and abdominal wound, oedematous fallopian tubes and their bisection. In 3 cases, Verres needle penetrated the colon but it was diagnosed before inserting the trocar and cannula. Cardiac and respiratory arrest occurred in one case each but the patients could be revived and there was no mortality. In 3 cases, laparoscopy had to be abandoned because the laparoscope could not be passed into the peritoneal cavity. The failure rate was 0.5 percent. PMID- 8473092 TI - An improved method for transpyloric placement of nasoenteric feeding tubes. AB - Post pyloric placement of small bore feeding tubes can be an elusive goal. Failure to achieve the post pyloric position can result in fatal complications. The following study presents a cost-effective, rapid technique for achieving post pyloric placement of feeding tubes utilizing gastric insufflation and right lateral decubitus positioning. Four study groups were identified. Group I utilized the new technique as first attempt (n = 21). Group 2 utilized the traditional, standard technique of insertion as first attempt (n = 20). Group 3 consisted of Group I failures after which the new technique was utilized (n = 19) Group 4 consisted of Group 3 failures after which the new technique was reattempted. Overall success rate of the new technique was 93%. This was highly significant with p < 0.0001. No significant difference was noted between inserters or type of tube used. The new technique described required no expensive equipment, minimal training and consistently allowed for transpyloric passage of the feeding tube. PMID- 8473093 TI - Esophago-rectal reflex. Description and clinical significance. AB - The present communication describes the "esophago-rectal reflex" and its clinical significance. The study was performed in 19 healthy volunteers and 14 constipated subjects. The technique comprised the introduction into the esophagus of a balloon-tipped tube so that the balloon lay within the lower esophageal sphincter (LES). The rectal and rectal neck pressures were measured by means of perfused open-ended tubes. The esophageal balloon was inflated with 2, 4 and 6 ml water and the responses of the rectal and rectal neck pressures were recorded. Distension of the LES was accompanied by significant rectal pressure increase (P < 0.001); the pressure increased with increasing LES distension. Anesthetized LES mucosa did not evoke the rectal pressure response. The rectal neck pressure did not show significant change with LES distension (P > 0.05). Both the rectal and rectal neck pressures showed insignificant response to LES distension in constipated subjects (P > 0.05). The esophago-rectal reflex seems to be conducted through the myenteric plexus from the esophagus down along the gut wall to the rectum, initiating rectal contractions. It is likely that these signals alarm the rectum for the entrance of new contents in the gut so that the rectum may evacuate its contents. PMID- 8473094 TI - Suturing techniques for a restricted operating space. AB - The movements of the needle holder and the needle do not correspond when the needle grip is modified for suturing in awkward sites. In this study the range of movement of the needle holder was determined for three modified grips and the optimum suturing methods were determined for horizontal and vertical suturing fields and for restricted and open operating spaces. Gripping a needle obliquely resulted in a 90 degree counterclockwise rotation of the range of movement of the needle holder. Gripping it after rotation deviated the needle holder without altering the range of movement. A combined grip achieved by rotating after shifting had an intermediate effect. The optimum suturing for a restricted horizontal operating space was to use a half-circle needle in the first half of its range of movement with the rotated grip. With the oblique grip the last half of the range should be used and in the middle the combined grip is used although gripping the needle is most stable with the oblique grip. For a restricted vertical operating space, the third quarter of the movement range was allotted to the rotated grip and the last quarter to the combined grip. PMID- 8473095 TI - [Renaissance of laparoscopic techniques in diagnosis of abdominal diseases]. PMID- 8473096 TI - [Therapeutic laparoscopy for the internist]. PMID- 8473097 TI - [The importance of conventional radiology in the current gastroenterology diagnostic concept]. PMID- 8473098 TI - [Computerized tomography in diseases of parenchymatous organs of the epigastrium- liver, pancreas, spleen]. PMID- 8473099 TI - [MR spectroscopy. Possibilities for the functional assessment metabolically active abdominal organs]. PMID- 8473100 TI - [Methods in nuclear medicine and their significance for diagnosis of gastrointestinal diseases]. PMID- 8473101 TI - [Electronic documentation of images and findings in gastroenterology]. PMID- 8473102 TI - [Right-sided epigastric pain and ascites in a 24-year-old female patient]. PMID- 8473103 TI - [Jaundice]. PMID- 8473104 TI - Introduction of Eliot L. Berson, 1992 Friedenwald Award winner. PMID- 8473105 TI - Retinitis pigmentosa. The Friedenwald Lecture. PMID- 8473106 TI - Determination of cellular types in the retina. PMID- 8473107 TI - Incremental light detection thresholds across the central visual field of human albinos. AB - PURPOSE: The authors investigated central retinal function in albinism by measuring incremental light detection thresholds in a group of oculocutaneous human albinos. METHODS: Eleven oculocutaneous human albinos (six tyrosinase negative and five oculocutaneous positive), six patients with idiopathic congenital nystagmus, and six normal control subjects participated in the study. Using a Goldmann bowl perimeter, incremental light detection thresholds were measured in the vertical meridian across the central +/- 30 degrees of the retina. Target presentation times were 1 sec for all subjects, and in the case of four albinos and one patient with idiopathic nystagmus, they were limited to the low-velocity period of each nystagmus cycle. RESULTS: For the normal control subjects, the maximum sensitivity was found to be -0.60 +/- 0.10 log units. By comparison, at 0 degrees, a range of sensitivities was obtained from the albino subjects (-0.9 to -2.1 log units) and from those with idiopathic nystagmus (-0.7 to -1.9 log units). The albinos had diverse retinal sensitivity profiles ranging from a near-normal peaked curve to a flat homogeneous profile. A variety of sensitivity profiles was also detected in those with idiopathic nystagmus, although, compared with the albino curves, a greater proportion were peaked. No sensitivity differences were found between the short and the longer target presentations. CONCLUSIONS: The variety of retinal sensitivity profiles obtained in this study suggests that, in albinism, considerable intersubject variability in the degree of foveal hypoplasia exists and that albino "foveal" function can reach near-normal levels, for at least some visual tasks. PMID- 8473108 TI - Magnification perimetry. AB - PURPOSE: The authors used a method of spatial scaling to quantify the eccentricity-related decline in differential light sensitivity as a function of visual field meridian and age. METHODS: Differential light threshold at the fovea was measured in two groups of subjects of differing age (young mean age, 23.6 yr; standard deviation, 2.4 yr; elderly mean age, 69.6 yr; standard deviation, 6.2 yr) using a Goldmann size I stimulus moving across fixation at 1 degree/sec. With luminance kept constant, eccentricity thresholds for kinetic stimuli of increasing magnification were then measured. The results were analyzed in terms of the E2 value, which specifies the eccentricity at which the stimulus size must double to maintain performance equivalent to that at the fovea. RESULTS: For the young subjects, eccentricity thresholds increased linearly with an increase in stimulus diameter for most meridians. E2 varied between 5-12 degrees, depending on the meridian, and showed the same meridional trend as that of retinal ganglion cell distribution, although the magnitudes of E2 were different. For the elderly subjects, the eccentricity thresholds increased in a nonlinear manner with the stimulus diameter. CONCLUSIONS: Further factors, such as spatial summation, must also determine the eccentricity dependence of the differential light threshold because ganglion cell density decreases at a much faster rate than the differential light threshold. The most marked effects of age on differential light sensitivity occur at the fovea and beyond 20 degrees in the peripheral field, with a relative sparing in the pericentral area. PMID- 8473109 TI - Quantitative evaluation of saccadic and smooth pursuit eye movements. Is it reliable? AB - PURPOSE: The authors evaluated the reliability of the coefficients of the (1) amplitude/duration and (2) amplitude/peak velocity relationships of the mean precision values and the mean latency values (saccadic eye movements) and the coefficients of the target velocity/gain relationship (smooth pursuit eye movements). They computed test-retest maximum variability limits for these parameters. METHODS: After a 1-week interval, saccadic and smooth pursuit eye movements were recorded twice from 20 healthy subjects; 12 of these subjects underwent a third recording session. The estimate of the intraclass coefficient of reliability, R, was adopted to evaluate the reliability of eye movement quantitative analysis. RESULTS: The data demonstrated that the reliability was fairly good for the amplitude/peak velocity relationship, was good for the precision, and was excellent for the amplitude/duration, the target velocity/gain relationships, and the latency. CONCLUSIONS: Quantitative analysis of both saccadic and smooth pursuit eye movements is reliable. One statistic used to estimate reliability, ie, the within-subjects mean square value, also enables the determination of test-retest normal variability values for both the variances and the differences of measurements. PMID- 8473110 TI - Predictive value of the pattern electroretinogram in high-risk ocular hypertension. AB - PURPOSE: The pattern electroretinogram (PERG) is reduced in early glaucoma and in some eyes with ocular hypertension (OHT). This study was designed to test the ability of the PERG to predict the development of visual field loss in OHT eyes. METHODS: In 29 eyes of 18 patients with high-risk OHT, the visual fields were tested, and the PERG was recorded using counterphasing checkerboard patterns at check sizes of 0.8 degrees and 15 degrees at 16 reversals/sec. The visual fields were retested 11-31 mo later. Initially, 12 eyes had pathologic PERG recordings. RESULTS: During the observation period, visual field loss developed in five eyes. All these eyes had a pathologic PERG recorded during the first visit. Of the eyes that had a normal PERG, none had field changes. CONCLUSIONS: Within the reservations of the limited sample size and follow-up interval, these findings suggest that the PERG can be used to discriminate between patients with OHT who will develop visual field loss and those who will not. PMID- 8473111 TI - Retinal blood flow by hydrogen clearance polarography in the streptozotocin induced diabetic rat. AB - PURPOSE: The authors compared retinal blood flow in rats after 5 weeks of streptozotocin (STZ)-induced diabetes with that in age-matched control animals. METHODS: The flow measurements were based on the hydrogen clearance technique and the intraocular placement microelectrodes at the surface of the retina. The hydrogen was delivered by bolus injection (100 microliters) of hydrogen-saturated saline into the ipsilateral carotid artery using a cannula through the lingual artery. The rats were anesthetized and artificially ventilated. Care was taken to match the systemic blood pressure and blood gases in the two groups. RESULTS: The mean retinal blood flow in the STZ group after 5-6 weeks duration of hyperglycemia was 487 +/- 59 ml/min/100g (standard error) compared with 330 +/- 16 ml/min/100 g in the age-matched controls. The variation in retinal blood flow was far more pronounced in the STZ group, even in different locations in the same eye. Changes in fundus appearance were also noted, with second-order arterioles being more apparent and the retina more "pinkish" in appearance in the STZ animals. CONCLUSIONS: The mean retinal blood flow in the region of retina studied in the two groups was significantly higher in the STZ animals than in age-matched controls. The increased heterogeneity of retinal blood flow may reflect a disruption to the normal blood flow control mechanisms in the retina after only 5 weeks of STZ-induced diabetes. PMID- 8473112 TI - Heterogeneity of endothelium-dependent regulation in ophthalmic and ciliary arteries. AB - PURPOSE: Endothelial cells modulate vascular tone by releasing the vasodilator nitric oxide (NO) or the vasoconstrictor endothelin-1. From one vascular bed to another and between vessels of different diameter, heterogeneities of endothelium dependent regulatory mechanisms exist. Hence, the current study compared the effects of NO and endothelin-1 in the porcine ophthalmic artery and one of its branches, the ciliary artery. METHODS: Porcine eyes were obtained at the slaughterhouse. The ophthalmic and ciliary arteries were dissected free under a microscope and suspended in myograph systems (95% O2 and 5% CO2, 37 degrees C) for isometric tension recording. RESULTS: In both vessels, bradykinin stimulated the release of NO, but the sensitivity to bradykinin increased with decreasing vascular diameter. By contrast, the basal release of NO became less efficient in inhibiting contractions to serotonin and endothelin-1 in ciliary versus ophthalmic artery. Endothelin-1 induced potent contractions that were more pronounced in ciliary than in ophthalmic artery. Serotonin-induced contractions also were more efficient in ciliary artery but less than to those to endothelin 1. Contractions to serotonin were inhibited in both blood vessels by the 5-HT2 serotonergic antagonist ketanserin. CONCLUSIONS: Thus endothelium-derived vasoactive substances are potent regulators of porcine extraocular ophthalmic circulation. Their effects increase with decreasing vascular diameter, suggesting an important role of NO and endothelin-1 in the regulation of ophthalmic circulation. A dysfunction of these regulatory mechanisms could have implications about the pathogenesis of ophthalmic complications seen in diabetes, hypertension, and in certain forms of glaucoma associated with ocular vasospasms. PMID- 8473113 TI - Electroretinographic results and ocular vascular perfusion in type 1 diabetes. AB - PURPOSE: Although functional changes in vision are known to occur before overt diabetic retinopathy, the relationship between (1) the degree and timing of any visual dysfunction and (2) the duration and control of diabetes remains poorly defined. The authors compared the ability of patients with insulin-dependent diabetes mellitus and nondiabetic subjects to sustain normal retinal function during transient physiologic stress. Such provocative testing may be clinically useful to show subclinical dysfunction. METHODS: Retinal function during altered ocular perfusion pressure (OPP) produced by body inversion and scleral suction was quantified by scotopic white-flash electroretinography (ERG) in 11 young volunteers with insulin-dependent diabetes mellitus but without significant retinopathy and a group of normal subjects. RESULTS: Baseline ERG a- and b-waves did not differ across test groups, but the a-wave implicit time was prolonged for diabetic patients. Furthermore, four of five oscillatory potentials (OP) in the diabetic patients were smaller than those in the nondiabetic subjects. Although the amplitude and implicit time of some OP in the diabetic patients were changed to a larger degree, the overall OP response profile did not differ widely from that for the nondiabetic subjects. Also, the a- and b-waves and the OP index for the test eye in diabetic and normal subjects did not differ, but the control eyes showed some differences in these parameters. CONCLUSIONS: Retinal function and vascular autoregulation in young diabetic patients without visible retinopathy did not differ from those in nondiabetic subjects; they were reduced in both groups by a short-term attenuation of the OPP. PMID- 8473114 TI - Microinjection of L-lactate in the preretinal vitreous induces segmental vasodilation in the inner retina of miniature pigs. AB - PURPOSE: The authors investigated the hypothesis that the retinal vasomotor effect of acute hypoxia is mediated by lactate. METHODS: Retinal vasomotor arteriolar response was measured in the intact eyes of miniature pigs after systemic administration and after local preretinal juxta-arteriolar microinjection of lactate. RESULTS: Injection of L-lactate (physiologically produced lactate) into the systemic circulation decreased the arterial blood pH but did not dilate the retinal arterioles. By contrast, microinjections of L lactate (0.5 mol/l, pH 2) into the juxta-arteriolar vitreous induced a reversible segmental vasodilation of 32 +/- 4% (standard deviation). This vasodilation did not depend on periarteriolar pH lowering because microinjections of a 0.5 mol/l L lactate at neutral pH also dilated segmentally the retinal arterioles (37 +/- 5.5%). The effect of lactate was stereospecific because microinjections of the isomer D-lactate (0.5 mol/l, pH 2) did not affect the arteriolar caliber (P = 0.63). Perfusion of the eye with the cyclo-oxygenase inhibitor indomethacin, through cannulization of the sublingual artery, caused a generalized reversible arteriolar vasoconstriction of 51 +/- 9.8% but did not inhibit the segmental vasodilator effect of locally microinjected L-lactate. CONCLUSIONS: It is known that acute hypoxia in the isolated retina causes an increase in lactate production. In the intact eye, there is a retinal vasodilation, which is not inhibited by indomethacin. Hence, it was concluded that retinal, but not blood, lactate is a possible mediator of the acute hypoxia-induced vasodilation. PMID- 8473115 TI - Aclacinomycin A in the treatment of experimental proliferative vitreoretinopathy. Efficacy and toxicity in the rabbit eye. AB - PURPOSE: Aclacinomycin A is an oligosaccharide anthracycline that, by contrast with daunomycin, lacks carcinogenicity. The authors evaluated the efficacy of aclacinomycin A in prevention of experimental proliferative vitreoretinopathy (PVR) and its toxicity on the rabbit retina. METHODS: Dutch-belted rabbit were used to create a model for traction retinal detachment. Seven to 10 days after vitreous gas compression, 25,000 homologous fibroblasts were injected into the vitreous cavity. Subsequently, the eyes received either sham injections or doses of 6, 30, or 60 nmol of aclacinomycin A, respectively. The fundus findings were documented on days 7, 14, and 28 after the fibroblast injection. The toxicity studies were conducted according to the same protocol as was used for the efficacy evaluation but without the fibroblast injection. Simultaneous electroretinograms were recorded on days 0, 3, 7, and 14 from the right eyes that were injected with 30 or 60 nmol of aclacinomycin A and the left eyes that were sham injected. Morphologic studies were conducted on the eyes enucleated on days 3, 7, and 14 after drug exposure. RESULTS: Intraocular administration of 30 nmol of aclacinomycin A on day 2 after fibroblast injection resulted in a detachment rate of 37.5% (controls, 100%; P < 0.01, by Fisher's exact test). Administration of 60 nmol of aclacinomycin A 3 days after fibroblast injection resulted in a detachment rate of 26.7% (controls, 100%; P < 0.0001). Six nanomoles of aclacinomycin A 3 days after fibroblast injection had no effect. No electroretinogram changes were present in eyes treated with 30 nmol of aclacinomycin A. Such recordings from eyes exposed to 60 nmol of aclacinomycin A demonstrated decreased a- and b-waves on day 3; these completely recovered by day 7. Morphologic studies of these eyes revealed no damage to the retina. CONCLUSIONS: These results suggest that aclacinomycin A should be considered an alternative to daunomycin for treatment of human PVR because, in addition to its lack of carcinogenicity, it shows good efficacy and causes less retinal toxicity. PMID- 8473116 TI - Stereopsis after congenital cataract. AB - PURPOSE: The authors determined whether stereopsis can be demonstrated in children treated for congenital cataract after compensating for their amblyopia and strabismus. METHODS: A custom-made set of large stereograms was used to compensate for amblyopia and presented in a synoptophore to facilitate motor fusion. Each pair of stereograms contained five wide vertical bars of high contrast, of which two or three were in crossed disparity. The authors aligned the stimuli in the synoptophore, then decreased the disparity until the child could no longer identify which bars appeared to be "in front." RESULTS: In normal children (n = 25), stereo acuity on this test (Tytla-Lewis-Maurer-Brent [TLMB] test) correlated well with the Titmus and Randot results within the ranges measured by those tests. Seven children in whom a traumatic cataract had developed after 6 yr of age (four with no clinical stereopsis) had TLMB test stereo acuities ranging from 225 to 28 arc-sec. Of 30 children treated for congenital cataract with no clinical stereopsis, 5 regularly achieved a TLMB stereo acuity of up to 225 arc-sec, and 2 with Titmus stereo acuities up to 200 arc-sec, each had a TLMB stereo acuity of 112 arc-sec. These seven congenital cases (two unilateral and five bilateral) with measurable TLMB acuities are among those with the shortest deprivation, the highest minimum resolvable acuity, and the highest contrast sensitivity. CONCLUSIONS: By compensating for amblyopia and strabismus, stereopsis can be demonstrated in some form-deprived amblyopic patients. PMID- 8473117 TI - The inhibitory effects of integrin antibodies and the RGD tripeptide on early eye development. AB - PURPOSE: The authors investigated the effects of probes that disrupt integrin extracellular matrix interactions on early eye development. METHODS: Antibodies and peptides that have been shown in other studies to block the interaction of cell surface integrins with various ligands were microinjected into the preoptic regions of chick embryos. Eye morphogenesis and biochemical differentiation of ocular tissue layers were assessed by histologic and immunohistochemical analyses. RESULTS: Antibodies that bind to the beta 1 subunit of integrin and block its function prevented normal eye morphogenesis but did not block expression of certain cell differentiation markers. The RGD tripeptide showed the same inhibitory capacity as did the anti-integrin antibodies. CONCLUSIONS: Integrin-based cell-cell and/or cell-extracellular matrix interactions are important in early eye morphogenesis. By contrast, certain aspects of tissue and cell differentiation, such as the expression of carbonic anhydrase II, are controlled independent of morphogenesis. PMID- 8473118 TI - Latent nystagmus. Release and suppression at will. AB - PURPOSE: The authors report the cases two unusual patients with infantile convergent strabismus and latent nystagmus. METHODS: Electronystagmography was used. RESULTS: The two patients were able to release and suppress their nystagmus at will. With voluntary effort, the nystagmus became as strong as it was when brought out by occlusion of the squinting eye and, in one of the patients, even stronger. The nystagmus beat toward the fixing eye, and the slow phases had slightly decreasing velocity or were linear. Both patients were able to evoke and to stop the nystagmus in front of visual contours and, one of them, also in the dark. CONCLUSIONS: This phenomenon could be the result of voluntary control of the visual input contributed by the amblyopic eye and/or a direct influence of will on the slow eye movement and fixation systems. A mechanism related to vergence eye movements is less likely. The ability to release and suppress a latent nystagmus at will is unusual and, to the authors' knowledge, has not been described before. PMID- 8473119 TI - Quantitation of total protein deposits on contact lenses by means of amino acid analysis. AB - PURPOSE: This study was done to characterize and quantify the protein deposits on worn contact lenses and to measure the residual deposits after extraction in 2% sodium dodecyl sulfate and the total protein deposits on worn vifilcon, atlafilcon, and tefilcon lenses (Food and Drug Administration Types IV, II, and I, respectively). METHODS: Contact lens extracts were separated with gel electrophoresis, and the amount of protein was estimated after silver staining and densitometry. To determine the residual deposits, the contact lenses were hydrolyzed, and amino acid analysis was carried out by reverse-phase high performance liquid chromatography after precolumn derivatization with phenylisothiocyanate. Refinement of the hydrolysis conditions was undertaken to minimize interference by the lens polymers. RESULTS: The extraction removed only approximately 25% of the protein deposits. Mild hydrolytic conditions, 20 hr in 6 N HCl at 105 degrees C, were found to cause minimal polymer interference. Of the 350, 10, and 20 micrograms of protein typically determined on whole vifilcon, atlafilcon, and tefilcon lenses, the polymers were estimated to account for 4, 0.5, and less than 0.4 micrograms, respectively. CONCLUSIONS: Hydrolysis of worn contact lenses with subsequent amino acid separation can be applied to determine the total protein deposits without the uncertainty inherent in extraction of the deposits. PMID- 8473120 TI - In vitro growth and differentiation of rabbit bulbar, fornix, and palpebral conjunctival epithelia. Implications on conjunctival epithelial transdifferentiation and stem cells. AB - PURPOSE: The anterior surface of the eye is covered by several physically contiguous but histologically distinguishable epithelial overlying the cornea, limbus, bulbar conjunctiva, fornix conjunctiva, and palpebral conjunctiva. It is important to determine whether the different phenotypes of these epithelia are the result of intrinsic divergence, extrinsic modulation, or a combination of both. Based on keratin expression and cell kinetic criteria, the authors previously suggested that corneal epithelial stem cells may actually reside in the limbal basal layer. METHODS: In this article, the relationship between the corneal-limbal epithelial cells and conjunctival epithelial cells was analyzed by comparing their growth and differentiation properties in an identical cell culture environment. RESULTS: Using Dispase instead of trypsin to dissociate the cells, the authors were able to grow all five rabbit ocular surface epithelia in the presence of 3T3 feeder cells. They found that corneal and limbal cells synthesize identical keratins, including large amounts of the K3 and K12 markers of corneal-type differentiation. By contrast, all three conjunctival epithelia shared another keratin pattern, with large amounts of simple epithelial keratins but only minute amounts of K3/K12 keratins. CONCLUSIONS: This observation, coupled with previous findings that the "transdifferentiation" of conjunctival epithelial cells to corneal epithelium appears to be both incomplete and reversible, provides strong evidence that (1) the limbal-corneal epithelial cells form a lineage distinct from the conjunctival lineage and (2) conjunctival transdifferentiation actually represents a process of environmental modulation. In addition, of the three types of conjunctival epithelial cells, fornix cells were found to have a much greater proliferative potential than bulbar and palpebral cells. This observation, coupled with recent finding that fornix is enriched in slow-cycling (label-retaining) cells, raises the possibility that conjunctival epithelial stem cells may preferentially reside in the fornix. PMID- 8473121 TI - Integrins in the wounded and unwounded stratified squamous epithelium of the cornea. AB - PURPOSE: The authors determined the synthesis, cell surface expression, and localization of integrins in the rat corneal epithelium to detect whether any changes in integrins occur during epithelial migration in response to simple debridement wounding. METHODS: Immunoprecipitation analysis of extracts from either metabolically or surface-labeled rat epithelia was done to assess the synthesis and cell surface expression of integrins in the normal cornea. The localization of integrins was determined by indirect immunofluorescence of frozen sections obtained from control corneas and from those after debridement wounding. Immunoblotting of extracts from time course experiments was done on organ cultures of rat corneas after debridement to determine if any changes in the amounts of integrins occurred. The cell adhesion function of integrins on control and migrating epithelial cells was evaluated by cell adhesion assays. RESULTS: The data indicated that the corneal epithelium has a variety of distinct integrin subunits including beta 1, beta 4, beta 5, alpha 2, alpha 3, alpha 5, alpha 6, and alpha v. Although beta 1, beta 5, alpha 2, alpha 3, and alpha v were localized to sites of apparent cell-cell contact, alpha 5, alpha 6, and beta 4 were localized specifically to the basal membrane of the basal cells. Little change occurred in the localization of integrins in the migrating epithelial sheets. At 3, 6, 9, 12, 18, and 24 hr after wounding, the amount of the beta 1, beta 4, alpha 3, alpha 5, and alpha 6 integrin subunits (as measured by immunoblots) was not altered relative to that of the control corneas. Adhesion assays also showed no differences in adhesion of stationary versus migrating corneal epithelial cells to fibronectin and laminin. CONCLUSIONS: Integrin localization, production, and cell adhesion function in the stratified squamous epithelium of the cornea are not dramatically altered during epithelial cell migration over simple debridement wounds. Integrins in the cell membrane at sites of cell-cell interaction and as components of the hemidesmosomes in stationary epithelia may be available for rapid recruitment as epithelial cell migration proceeds. PMID- 8473122 TI - Expression of basic fibroblast growth factor and its receptor in the retina of Royal College of Surgeons rats. A comparative study. AB - PURPOSE: The aim of this study was to identify whether abnormalities in the synthesis of basic fibroblast growth factor (bFGF) or its receptor (bFGF-R) were responsible for the photoreceptor dystrophy in Royal College of Surgeons (RCS) rats. METHODS: The polymerase chain reaction was used to detect the expression of bFGF and bFGF-R messenger RNA in the retinal pigment epithelial (RPE) cells and the neural retina of RCS dystrophic rats and in PVG/C and RCS-rdy+ control animals. RESULTS: In the RPE, it was found that there was no significant difference in the expression of bFGF and bFGF-R between RCS rats and the controls at the ages of 21 days and 3 mo. In the neural retina, the level of bFGF expression was lower in the 21-day-old RCS rats compared with the control group, but bFGF-R expression was as strong as in the PVG/C and RCS-rdy+ animals. However, in 3-mo-old RCS rat neural retina, the bFGF and bFGF-R expression was found to be significantly lower than in the control animals. CONCLUSIONS: Although the mutant gene in RCS rats is expressed in the RPE cells, these results suggest that there is no significant defect in bFGF or bFGF-R expression in the RPE cells of RCS rats, which would be an initiating factor in the development of photoreceptor degeneration in these animals. The lowered bFGF levels in the neural retina at early stages (postnatal day 21) may explain the prolongation of photoreceptor survival when exogenous bFGF is injected. PMID- 8473123 TI - Correlation between the physiologic and morphologic changes in experimental autoimmune uveitis induced by peptide G of S-antigen. AB - PURPOSE: The authors followed and correlated the physiologic and morphologic changes occurring in experimental autoimmune uveitis (EAU) induced by the peptide G of S-antigen. METHODS: EAU was induced in Lewis rats by footpad inoculation of a 13-amino acid synthetic peptide (peptide G) in complete Freund's adjuvant. Electroretinography (ERG) was used to follow the physiologic changes, and light and electron microscopy were used to examine the morphologic changes. RESULTS: Serial ERG recordings showed a progressive decrease in the b-wave amplitude and a depression of retinal sensitivity beginning on day 18-21 postinoculation (PI). By day 35 PI, the b-wave was decreased by 91%, and the sensitivity was depressed by 4.68 log units. Negative ERG were recorded during the intermediate and late stage. Light and electron microscopy of the retina showed better correlation of the pathologic changes with b-wave depression than with PI day. CONCLUSIONS: ERG recordings were a good method to detect, follow, and quantify the severity of EAU. Their good correlation with the morphologic changes showed that this method can be used to assess the condition of the retina noninvasively. PMID- 8473124 TI - Simulation of corneal neovascularization by inverted diffusion limited aggregation. AB - PURPOSE: The authors modeled the normally avascular mammalian cornea response to injury by neovascularization. The nature of this process remains obscure, although diffusion mechanisms are thought to be involved. METHODS: Corneal neovascularization was simulated using fractal stochastic computer models for nonequilibrium diffusion (inverted diffusion limited aggregation) and a stochastic ballistic aggregation. RESULTS: The inverted diffusion limited aggregation model was found to generate patterns strikingly similar to those observed in pathologic neovascularization of the cornea in vivo. CONCLUSIONS: This result supports the role of random diffusion mechanisms modified by environmental factors, such as the release of angiogenic factors in corneal angiogenesis. PMID- 8473125 TI - Single-cell contraction assay for human ciliary muscle cells. Effect of carbachol. AB - PURPOSE: The authors developed an assay to observe the contraction of a single human ciliary muscle cell. METHODS: Cultured human ciliary muscle cells were partially detached from the culture dish by incubation with a nonenzymatic dissociation buffer and treated with carbachol or pilocarpine. Contraction was quantified by measuring the cross-sectional surface areas of the cells. RESULTS: Carbachol decreased the cell surface area in a time-dependent manner. Contraction was observed within 1 min after the addition of carbachol and completed in less than 15 min. The effect of carbachol was dose dependent. For example, at 10 min after treatment with 10 mumol/l carbachol, the relative surface areas of cells decreased to 47% +/- 4% (mean +/- standard error of the mean, n = 7, with surface area at 0 min defined as 100%). The relative surface areas were 74% +/- 4% (n = 7) after 1 mumol/l and 100% +/- 9% (n = 7) after 0.1 mumol/l carbachol treatment. This contractile effect was antagonized by pretreatment with atropine, a specific muscarinic antagonist. CONCLUSIONS: A simple method was established to study the functional changes of human ciliary muscle cells. PMID- 8473126 TI - Whatever happened to abstracts from different sections of the association for research in vision and ophthalmology? AB - PURPOSE: The authors investigated the fate of abstracts from each ARVO section (May 1985 meeting), the overall publication percentage, and the journals in which the abstract-derived articles were published. METHODS: They performed a MEDLINE search by first author for 25 or 26 randomly selected abstracts from each section to identify those that led to full-length articles in peer-reviewed journals. RESULTS: Overall, 63% of abstracts led to full-length articles in peer-reviewed journals within our search period of 87 months. The publication rate of oral presentation abstracts (68%) was significantly higher than that of poster presentation abstracts (56%). A greater proportion of basic science-oriented abstracts (67%) led to publication than the clinically oriented abstracts (56%). The rate of publication was lowest for the Cornea section (40%) and highest for Physiology and Pharmacology (80%) and Biochemistry (76%). The abstract-derived articles were published in 67 different peer-reviewed journals, with 43% of the articles appearing in only five journals. CONCLUSIONS: The fact that the majority of abstracts led to full-length articles supports ARVO's goal of a large interdisciplinary appeal with the exchange of ideas among different investigators. PMID- 8473127 TI - A comparison of SPECT and planar ventilation perfusion lung scanning. AB - In order to define the role of Single Photon Emission Computed Tomography (SPECT) in the diagnosis of pulmonary embolus; SPECT and Planar ventilation and perfusion lung studies were performed consecutively on eleven patients referred with suspected embolus. Three patients were shown to have 'high probability' ventilation perfusion mismatches. SPECT imaging allowed segmental localisation of the perfusion defect and revealed additional defects not seen on planar scans. SPECT lung study was performed with minimal technical difficulty and was well tolerated by all patients studied. SPECT is likely to become the method of choice for investigating patients referred with suspected pulmonary embolus. PMID- 8473128 TI - A case report of an Irish family displaying nail-patella syndrome. AB - This is a case report of an Irish family displaying classical features of Nail Patella Syndrome--also known as Osteo-onycho Dystrophy--involving four members over three generations. This rare autosomal dominant disorder is well defined with four classical characteristics: dysplasia of finger nails, hypoplastic or absent patellae, hypoplasia of the head of the radius and often the capitulum of the humerus leading to subluxation or dislocation of the radial head and iliac prominences, known as iliac horns which are usually bilateral and symmetrical. Renal dysfunction is also commonly reported. This is the first report of the Nail Patella Syndrome in an Irish family. PMID- 8473129 TI - Thoraco-abdominal aortic aneurysm replacement using hypothermic circulatory arrest. PMID- 8473131 TI - The management of hyperlipidaemia. PMID- 8473130 TI - Prevalence of metronidazole-resistant Helicobacter pylori in dyspeptic patients. AB - Susceptibility to metronidazole of 213 clinical strains of H. pylori from dyspeptic patients was determined by a plate dilution method. Seventy two (33.8%) of the strains were resistant to metronidazole (MIC > 8 mg/L), 20 of these were from 24 patients who had received previously metronidazole (83.3%), giving a primary (pretreatment) resistance rate of 27.5% (52/189). The resistance rate was higher in women than in men, especially aged 50 to 59 years old (43.6% vs 23.3%, p < 0.001). The resistance rate was lower in patients at 60 or over (9.8%), but similar between the younger patients groups (38.8% - 49.0%). There was no difference in the resistance rate between peptic ulcer disease (32.6%) and nonulcer dyspepsia (34.7%). These data indicated that metronidazole resistance in H. pylori is absolutely associated with previous use of the drug, and the higher resistance rate in women may be due to the more frequent prescription of the drug for their gynaecological infection or operation. Therefore, testing of susceptibility of H. pylori to metronidazole is important. A new susceptibility testing technique, the E-test was evaluated in this study and found to give comparable results to the plate dilution method and also had the advantage of being simple to perform. PMID- 8473132 TI - Management of congestive cardiac failure. PMID- 8473133 TI - Management of mild to moderate hypertension. PMID- 8473134 TI - Angiotensin converting enzymes inhibitors in heart failure. PMID- 8473135 TI - The management of chronic epilepsy. PMID- 8473136 TI - The use of primary care services by drug users attending a HIV prevention unit. AB - Intravenous drug using clients of a Dublin HIV Prevention Unit were interviewed about their use of general practitioner services. Sixty eight percent of clients had visited a GP within the previous year and 48% were registered with a GP under the General Medical Services (GMS) Scheme. Of 161 interviewees 60 were being treated with a fixed dose regimen of methadone at the Prevention Unit; this group was far less likely to visit a GP with a drug related problem and far less likely to have received methadone from a GP. Members of the GMS were much more likely than non members to have visited a GP and also more likely to have attended a specific GP for all problems besides methadone treatment. Methadone treatment and medical cover within the GMS Scheme emerged as important influences on the behaviour of clients with respect to general practitioners. PMID- 8473137 TI - A review of triplet pregnancy. AB - Nineteen sets of triplets were delivered in the National Maternity Hospital between January 1st 1980 and December 31st 1990 inclusive. Thirteen triplet pregnancies resulted from spontaneous ovulation and six from ovulation induction therapy for infertility. Management was conservative. Bed rest and home monitoring were not advised routinely and cervical cerclage and tocolytic agents were not used. Ten of the patients were delivered by caesarean section. The prematurity rate was 79% and five sets of triplets were delivered before 32 weeks gestation. The perinatal mortality rate was 35/1000. This reflects a general improvement in the obstetric and neonatal care of triplet pregnancy over the past decade. PMID- 8473138 TI - A case control study of malignant melanoma. AB - A case-control study of 100 cases of malignant melanoma (MM) and 100 matched controls has been completed. The male:female ratio of patients with MM was 1:2.4, which is similar to that found in other European studies and the mean age was 49.1 years (range 19-82 years). Significant differences were seen between cases and controls for area of residence and social class, more cases than controls came from rural areas (P = 0.007) and cases were of higher social class than controls (P = 0.003) and had attained a higher level of education (P = 0.005). Phenotypic differences between cases and controls were also observed, namely cases were more likely to have light coloured (blue/grey/green) eyes (P = 0.003) and to have had fair/red hair at age 20 (P = 0.004). Cases were also more likely than controls to dislike exposure to hot sun (P = 0.008) to report sunburning easily (P = 0.001) and to have experienced episodes of sunburn with blistering more frequently than controls (P = 0.01). History of longterm exposure to ultraviolet radiation (UV) through working outdoors, leisure activities, living abroad in sunny climates, or sun holidays was similar between cases and controls. This study supports evidence from elsewhere that episodes of acute sunburn in susceptible individuals increase risk of MM and that longterm regular exposure to UV which is important in non-melanoma skin cancer does not play a major role in the development of MM. PMID- 8473139 TI - Socioeconomic factors and mortality in small areas. AB - The aim of this study was to determine the extent to which variation in socioeconomic factors derived from the 1986 census could "explain" variation in standardised mortality ratio (SMR) between the 322 electoral wards and district electoral divisions (DEDs) in Dublin. Factors examined included percentage of population in the various Irish social class groupings, percentage of male unemployment, number of cars per private household and number of persons per car. Regression analysis between SMR and each of these factors individually showed a significant relationship in every case. The explanatory variables studied were all highly correlated and stepwise forward multiple regression was used to identify factors which had an independent effect. Two factors emerged as significant--percentage of persons in social classes 5 & 6 (semiskilled and unskilled) and number of cars per private household. This model explained 27.4% of the variance in SMR. We conclude that the variation of SMRs between DEDs in Dublin can partly be explained by variation in socioeconomic factors. PMID- 8473140 TI - Long term home oxygen; current practices in Ireland. AB - We set out to determine the number of patients being provided with LTOT by the community health services and to review the criteria which are required to be fulfilled before LTOT will be provided by these services. We also wished to determine whether concentrators or cylinders were in use; how LTOT was managed and monitored and assess any possible savings to the health service if all patients were supplied with oxygen concentrators rather than cylinder supply. PMID- 8473141 TI - Self poisoning: admission to intensive care over a one year period. AB - The charts of all cases of self-poisoning admitted to an intensive care unit over one year are reviewed Two distinct groups are seen, according to the substances ingested The group who took prescription medications tended to be younger, and had a better outcome Those poisoned with household or industrial products were older, had a longer stay in intensive care, needed more intensive therapy and organ support and had a higher mortality. PMID- 8473142 TI - HLA typing in Irish psoriatics. AB - Histocompatibility antigens were determined in 93 unrelated Irish psoriatic patients. The results were compared with the HLA profiles of 253 healthy unrelated Irish controls. There was a statistically significant increase in HLA B17 (P < 0.0001), B13 (P = 0.02), and B27 (P = 0.015) among the psoriatic patients. The frequency of HLAB8 (P = 0.002) and HLA B12 (P = 0.001) was lower than expected. When the subgroup of patients with psoriatic arthritis was evaluated separately, it was noted that the increase in HLAB27 was highly statistically significant (P < 0.0001). The relative risks of an Irish patient carrying the major psoriasis associated alleles of developing psoriasis are documented;-possession of the HLA B17 and B13 antigens conferring a risk of developing psoriasis vulgaris of 6.08 and 2.9 respectively. Further values for psoriatic subsets are presented. This is the first report of HLA typing in an Irish psoriatic population. The findings are discussed and compared with other population groups. PMID- 8473143 TI - Clinical applications of echocardiography in patients with acute myocardial infarction. AB - The ability of echocardiography to visualize ventricular wall motion abnormalities induced by ischaemia and infarction makes it an ideal tool in the assessment of patients with acute myocardial infarction. Echocardiographic derived measurements of infarction severity, such as the wall motion score index, correlate well with both early and late complications. Echocardiography is of considerable value in the detection of mechanical complications of myocardial infarction such as aneurysm and thrombus formation, infarction expansion, ventricular septal rupture and mitral regurgitation; Doppler echocardiography is of particular worth in the detection of the latter two complications. Serial echocardiographic imaging before and after various coronary reperfusion strategies allows useful assessment of the success of these strategies. Following a myocardial infarction, a predischarge resting or exercise 2-dimensional echocardiographic study provides valuable information regarding the likelihood of adverse cardiac events during long term follow-up. PMID- 8473144 TI - Do not resuscitate orders in an Irish teaching hospital. AB - A chart review was performed to determine the resuscitation status of all in patients in this hospital on a single day. A decision not to resuscitate had been made for 11 (3.7%) of 293 patients. Seven of these patients had a severe stroke, two had dementia and one had a malignancy. We identified a further 22 patients who would be unlikely to benefit from resuscitative efforts but who had not been excluded from resuscitation: four patients with major impairment following a stroke, five patients with severe dementia and 13 patients with incurable malignancy. A policy of routinely discussing and documenting the resuscitation status of patients might reduce the unnecessary performance of cardiopulmonary resuscitation. PMID- 8473145 TI - Do elderly patients mind how doctors address them? AB - A survey was carried out in the Geriatric Unit at Cork Regional Hospital to determine how elderly patients would like to be addressed by their doctor. Two hundred patients over the age of 65 were given a Questionnaire asking them to state their preference. Only a minority (4.5%) expressed a definite preference for the formal mode of address. The remainder either did not mind (38%) or preferred to be addressed by their first name (57.5%). We concluded that most elderly patients do have a preference and this should be established on admission. PMID- 8473146 TI - Very long term retention of bronchial foreign bodies two new cases and a review of the literature. AB - We report two cases in which foreign bodies were retrieved from the bronchus after intervals of 25 years or more. Both occurred in women in their 30s, in neither case was there a history of aspiration, and both patients were asymptomatic for many years. The literature on protracted retention of bronchial foreign bodies is reviewed using a Medline search and relevant bibliography. PMID- 8473147 TI - Breast screening. PMID- 8473148 TI - Infection and the role of the clinical microbiologist. PMID- 8473150 TI - Copying procedures in focal brain-damaged patients. AB - We aimed to ascertain whether non-apraxic, focal brain-damaged patients used abnormal constructional procedures. We tested a series of consecutive patients, classified according to lesion locus and side against a matched sample of normal volunteers. Subjects had to copy the Rey-Osterreith Figure, a complex and structured item that explores copying strategies. We used special testing and scoring methods to analyze different steps of the copy. Unlike the controls, the patients did not choose the central elements of the figure as guiding structures. All patient groups followed an equivalent "pathological", "piecemeal" procedure. PMID- 8473149 TI - Clinical study of large kindreds with autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) of late onset. AB - Six families with SCA1 were studied. The clinical data on 35 patients are reported. Cerebellar and pyramidal system involvement was invariably found in association with brainstem, spinal cord and/or peripheral nervous system disorders. In our patients the clinical features appeared concordant when the patients with the same disease duration were compared. Previous reports of SCA1 families had shown great variability in clinical phenotype both interfamilial and intrafamilial. We suggest that the phenotype might appear more homogeneous if disease duration is taken into account. PMID- 8473151 TI - Meningiomas in elderly patients. Clinico-therapeutic considerations. AB - This study examines the immediate and long-term results of surgical treatment for intracranial meningioma in patients aged 65 and over. Average patient age was 69 years. The most frequent localizations were the convexity (29.8%) and the sphenoid wing (20.1%). Preoperative risk factors included hypertension (16.1%), cardiopathies (16.1%), diabetes (12.9%) pneumopathies (12.9%) and peripheral vascular diseases (9.6%). All patients were assessed according to the Karnofsky Performance Status (KPS). Operative mortality was 18.5% (23 cases). At long term follow up (minimum 4 months, maximum 12 years, average 5 years) 31.5% of patients were cured, 32.3% had improved and 4% had worsened. The risk factors that mainly influenced results included poor preoperative clinical condition as expressed by low KPS, while the most frequent medical postoperative complications that increased the rate of operative mortality were brain edema, infections and lung embolism. PMID- 8473152 TI - Amyotrophic choreo-acanthocytosis: a neuropathological and immunocytochemical study. AB - A 47 year old man, one of a sibship affected by amyotrophic choreo-acanthocytosis was studied neuropathologically after some years of clinical observation. Besides the classic optical findings (neuronal loss, astrocytic gliosis and "status spongiosus" in the basal ganglia, namely in the caudate nucleus) a few MEnk+ and NPY+ neurons were observed immunocytochemically in the striatum. In the spinal cord also, while no neuronal loss was perceivable, both mild demyelination and interfibrillary astrocytic hyperplasia of the long tracts were present. On the other hand, microscopic findings of muscle and peripheral nerve showed no differences from what was previously intra-vitam appreciated in the same patient. The neuropathological and immunocytochemical findings of this case are discussed in relation to the differential diagnosis between amyotrophic choreo acanthocytosis and Huntington's disease. PMID- 8473153 TI - Before M.A.S.T.-I: analysis of the population of a participating center. AB - Between 1 January 1989 and 31 December 1990 568 consecutive patients were admitted to our unit for ischemic stroke (defined on clinical criteria and with CT or MR evidence of ischemic areas or exclusion of hemorrhage or tumor). The interval between onset of symptoms and arrival in hospital was under 6 h in 270 cases (47.5%). We classified our population according to the clinical criteria proposed by Bamford et al. by subgroup as follows: LACI (27.5%); PACI (24.5%); TACI (30.6%); POCI (17.4%). The mortality in our population was 10.9%. The distribution of the risk factors considered was: hypertension in 387 cases (67%), diabetes in 158 cases (27.8%), NVAF in 95 cases (16.7%). Our data show that about a half of all patients with ischemic stroke can expect to receive treatment at the acute stage. PMID- 8473154 TI - Neuro-Behcet: clinical features and MRI correlates. AB - This paper highlights the fundamental role of MRI in the diagnosis of Neuro Behcet disease. We present 4 cases examined between 1990 and 1991. Treatment in all the cases seems to have improved the patients' prognoses. PMID- 8473155 TI - Multifactorial study of inflammatory myopathies. Report of 29 cases. AB - We made a comparative clinical, immunopathological and therapeutic evaluation in 17 patients with polymyositis (PM) and 12 patients with dermatomyositis (DM), followed up at our Neuromuscular Center. DM can be distinguished by its clinical appearance and pathological changes. Current evidence suggests that it results from vasculopathy. For studying these inflammatory myopathies we used multifactorial diagnostic criteria, evaluating the therapeutic response by means of a composite clinical and functional score in a longitudinal study. In muscle biopsy specimens we characterized with monoclonal antibodies T lymphocyte subpopulations (CD4, CD8), macrophages, IgG, IgM, C1q, C3, C4 complement fractions, MHC-I, MHC-II. In PM the cell-mediated immunity was more pronounced and in some cases both MHC-I and MHC-II molecules were found on the surface or within muscle fibers. Our patients were treated with steroids; in resistant cases azathioprine, cyclophosphamide, plasmapheresis, high-dose intravenous immunoglobulins (ivIgG) and total body irradiation were added to the therapeutic schedule. PMID- 8473156 TI - Cryptococcal meningoencephalitis in a non immunocompromised patient: case report with necropsy. PMID- 8473158 TI - Ethical considerations regarding overinvestigation in neurology. PMID- 8473157 TI - Category-specific deficits for grammatical classes of words: evidence for possible anatomical correlates. AB - Several neuropsychological studies have shown that brain-damaged patients may demonstrate category-specific deficits for grammatical classes of words, such as nouns and verbs. We describe 3 patients with selective impairments of these latter categories. The first patient, with marked atrophy of the left temporal lobe, was disproportionately impaired in naming and comprehension of nouns. The second patient, with a predominantly left frontal lobe atrophy, was selectively impaired in naming and comprehension of verbs. The third patient, with a left frontal lobe perfusion abnormality, had a selective impairment in naming and comprehension of verbs. Evidence from the present study support the hypothesis that anatomically distinct neural systems in the temporal and frontal lobes of the dominant hemisphere might play a critical role in lexical processing of nouns and verbs respectively. PMID- 8473159 TI - Strongyloides infection in Hawaii: an imported case. AB - Tropical diseases may present anywhere in the world. A case of strongyloidiasis in Hawaii, identified by a characteristic manifestation, larva currens, is described. Strongyloides infection may persist long after leaving an endemic area through the mechanism of autoinfection and, especially under circumstances of immunosuppression, may become overwhelming (the hyperinfection syndrome), with a likelihood of being fatal. Each case of Strongyloides infection should be treated aggressively in order to prevent this dangerous outcome; in addition, the parasite should be eliminated before immunosuppressive therapy is begun. PMID- 8473160 TI - A rare case of cholera in Hawaii. AB - Cholera is the most fatal of the infectious diarrheas but only rarely encountered in Hawaii. Two cases previously have been documented in the Islands. We describe an elderly patient, without obvious risk factors, who contracted cholera. Early consideration of cholera as a diagnostic possibility is recommended in patients with unexplained, profuse diarrhea. The unique features of this case are discussed in this report. PMID- 8473161 TI - Do we need second generation lithotripters in Hawaii? AB - The Kidney Stone Center of the Pacific (KSCoP) currently provides statewide services for kidney lithotripsy. The non-invasive technique uses shock waves to disintegrate kidney stones. Extracorporeal shock wave lithotripsy (ESWL) can be used successfully in 85% to 90% of kidney stone patients when surgery is indicated. PMID- 8473162 TI - [The dynamic hip screw support plate for management of unstable proximal femoral fractures]. AB - The DHS-Implant system is a technically simple and widely used operative treatment modality for pertrochanteric fractures of the femur. In unstable 4 part fractures rotation of the head and neck fragment around the lag screw and a significant impaction might lead to a lateralisation of the greater trochanter and therefore to an important shortening. To prevent these effects we treated 17 patients with 4 part-fractures with a prototype of a modular trochanteric DHS buttress plate. With this additional implant the lateralisation of the greater trochanter could be prevented in all cases. This also leads to a limitation of the telescoping, with less shortening even with immediate full weight bearing. PMID- 8473163 TI - [The gamma nail--an ideal implant for treatment of unstable fractures in elderly patients]. AB - Altogether we used the Gamma-Nail in 150 cases. We show here a series of 50 instable pertrochanteric femur fractures in very old patients which we treated with a Gamma-Nail. All cases started with full weight bearing at the 4th day after operation. A clinical and radiological control 12 weeks later shows good mobilisation of the hip in 70% of the cases. Shortening of the operated leg is rare in comparison of cases treated with a DHS. Two thirds of the patients returned after dismission of the hospital to the old social situation. The advantages in treating instable pertrochanteric femur fractures with the Gamma Nail are immediate full weight bearing without risks of shortening of the operated leg and the closed reduction of the fracture. PMID- 8473165 TI - [Osteosynthesis in dislocated femoral neck fracture (Garden 3 and 4). Long-term results and treatment concept]. AB - The dislocated fracture of the femoral neck (Garden type 3 and 4) in the young patient is preferably treated by open reduction and internal fixation. In the period 1980-1989 we fixed 49 fractures with a dynamic hip screw, a 130 degrees angled plate, screws alone, or by a valgisation osteotomy fixed with a 120 degrees-plate (Pauwels osteotomy). 30 fractures were reviewed after 66 months in average. We observed radiological signs of femoral neck necrosis in 9 patients, thereof 7 with symptoms, and radiological signs of osteoarthritis in 3 patients, two with symptoms. The possible factors causing these late complications are discussed. We advocate the immediate open reduction to evacuate the intracapsular hematoma into a slight valgus over-correction for stability. For the fixation we use 3 screws in good bone quality, the dynamic hip screw and the angled plate in osteoporotic bone often combined with an accessory screw for rotational stability. The functional long-term result was good or excellent in 70%. By avoiding technical errors this rate can be improved. PMID- 8473164 TI - [Management of femoral neck fractures at the Liestal canton hospital]. AB - The mode of treatment for femoral neck fractures at the Kantonsspital Liestal depends on age primarily. Patients over 70 years of age are treated with a unipolar endoprosthesis. Screws are being used in cases of medial femoral neck fractures, DHS in cases of lateral fractures. Total hip arthroplasty is only indicated in patients with evident osteoarthritis. 78 femoral neck fractures were seen in a 3-year-period. 50 endoprostheses were used in 49 patients. The mean age at time of surgery was 80 years. 70% of the patients have died at a mean survival time of 2 1/4 years. 13 out of a total of 14 surviving patients were investigated. The follow-up of 10 surviving patients reveals radiographically a mild protrusion in one case only. Clinically all 13 surviving patients are not compromised by the endoprosthesis after 5 years. We consider the implantation of a unipolar endoprosthesis in patients with femoral neck fractures at age over 70 years the treatment of choice. There is an acceptably low risk for protrusion as a late complication in regard to a reduced life expectancy. PMID- 8473166 TI - [The dynamic hip screw (DHS) in femoral neck fractures]. AB - Out of 224 patients with femoral neck fractures, 40 patients have been treated by ORIF with the dynamic hip screw, whereas 27 have been fixed by large cancellous bone screws and 148 femoral heads were replaced by a prosthesis. The ORIF with dynamic hip screw has been performed as an emergency intervention within 6.2 hours after accident. Good general condition without contraindication against an emergency operation as well as a biological age below 65 years and no pre existing coxarthrosis are mandatory for the indication for open rigid internal fixation. Personal follow-up of 37 patients with x-ray documentation after at least 18 months (mean 35.4 months) showed complete rehabilitation in 31 patients and 4 femoral head necrosis (10.8%). We conclude that these good results are due to the short interval between accident and operation as well as to the evacuation of the intraarticular hematoma together with stable internal fixation and functional rehabilitation. Due to our good results we prefer long cancellous bone screws for the operative fixation of femoral neck fractures in younger patients, whereas in the older group the dynamic hip screw is preferred. PMID- 8473167 TI - [Fractures near the femur head in children and adolescents]. AB - 13 patients (1981-1991) between 1.5-15.5 years (average 10.2 years) with Delbet I III fractures were analysed of the incidence of avascular necrosis. Only one (type II fracture) of our 13 patients was associated with a severe complication (Ratliff type I) of an avascular necrosis of the femoral head. This satisfactory result may be explained by our concept of immediate open reduction and minimal internal fixation of the displaced fractures. PMID- 8473168 TI - [Primary management and problems with osteosynthesis of subtrochanteric fractures of the femur]. AB - From 1986 to 1991 we treated 63 patients with subtrochanteric fracture of the femur. The etiology in 53 patients with 40 fractures mostly pedestrians, hit by a car; or motor vehicle accidents, in other words high velocity injuries that resulted in a significant number of multiply injured patients of whom 38 were polytraumatized, by our definition a multiply injured person with a life threatening injury of at least one of the following body parts: head, neck, thorax, abdomen, spine, extremities with neurovascular compromise and pelvic girdle. PMID- 8473169 TI - [Laparoscopic cholecystectomy in a medical training center. Apropos of 208 interventions]. AB - Laparoscopic cholecystectomy is a relatively recent acquisition and still remains limited to few surgeons. We started an education program for surgeons used to open biliary surgery. Between september 1990 and december 1991, 208 patients have been operated on by 14 operators flanked by 2 teachers. Technique was standardized and all patients were looked preoperatively for absence of stones in bile ducts using i.v. cholangiography and tomography. Only 6 patients (< 3%) needed to be converted to laparotomy. Morbidity was less than 6% and due to minor complications. Only one patient needed a reoperation because of incisional hernia. Mortality was null. Mean postoperative hospitalization time was less than 3 days. We conclude that laparoscopic activity in a teaching center allows acquisition of a new technique modality while remaining safe for patients. PMID- 8473170 TI - [Biliary pancreatitis--a good indication for laparoscopic cholecystectomy]. AB - Recently the indication for laparoscopic cholecystectomy has been enlarged to include biliary pancreatitis. While a majority of reports recommend early open cholecystectomy for biliary pancreatitis the use of laparoscopic cholecystectomy in this disease has not yet been discussed. We retrospectively reviewed 52 patients with biliary pancreatitis being admitted to our ward in the last five years. Cholecystectomy was performed in 48 patients. Ten had undergone laparoscopic cholecystectomy. Postoperative complications occurred in 8 of the 48 patients (16.6%). Four patients (8.3%) died due to necrotizing pancreatitis or rupture of pseudocysts. We found a correlation between morbidity and mortality and the prognostic score as well as the presence of pseudocysts. We conclude that biliary pancreatitis is a good indication for laparoscopic cholecystectomy in patients with a low prognostic score. The presence of pseudocysts in our view is no contraindication for laparoscopy. Although it may increase postoperative morbidity. Choledocholithiasis has to be ruled out either by preoperative ERCP or during laparoscopy with intraoperative cholangiography. PMID- 8473171 TI - [Laparoscopic versus conventional appendectomy: a comparison]. AB - We compared two groups of patients with acute appendicitis, from whom the first one had been operated conventionally, the second group by laparoscopy. There was no difference between the two groups regarding length of hospital stay, local and general complications. Only the operating time was quite longer in the laparoscopic group. In our experience laparoscopic appendectomy is an easy and safe procedure which can allow young surgeons to be properly trained in laparoscopic techniques. PMID- 8473172 TI - [Bile duct injuries in laparoscopic cholecystectomy]. AB - We report on three patients with iatrogenic lesions of the common bile duct after laparoscopic cholecystectomy. In one patient, an additional occlusion of the hepatic artery was found. The leading postoperative signs were jaundice and cholangitis. Endoscopic and radiologic intervention failed to correct the common bile duct stenosis in all three patients. Surgical correction by hepaticojejunostomy was successful, although the postoperative follow-up is still short. PMID- 8473173 TI - [Mirizzi syndrome--a contraindication for laparoscopic surgery]. AB - The Mirizzi syndrome refers to a benign obstruction of the common hepatic duct by a stone impacted within the cystic duct or the neck of the gallbladder causing an obstructive jaundice. According to McSherry's subclassification based on endoscopic retrograde cholangio-pancreatography we distinguish a type I, involving an external compression of the common hepatic duct by a large stone impacted in the cystic duct or Hartmann's pouch without lesion of the gallbladder or the common hepatic duct wall. In type II a cholecysto-choledochal fistula is present, caused by a calculous which has already eroded partly or completely into the common bile duct. The type I is better treated with a partial cholecystectomy, the type II with a partial cholecystectomy and a bilio-digestive anastomosis. Due to a severe inflammatory process with dense adhesions and odematous changes of the hepato-duodenal ligament, it is dangerous to prepare the Calot's triangle, in case of conventional cholecystectomy and/or in case of laparoscopic cholecystectomy. From 1986-1991 we have successfully treated 10 patients according to this concept (7 patients with type II, 3 patients with type I). We have no mortality and no lesion of the biliary system. One patient has been reoperated because of a postoperative hemorrhage and biliary fistula. One patient developed a benign stricture which could be dilated two months after the procedure. Two patients were found with an incidental carcinoma of the gallbladder. PMID- 8473174 TI - [Laparoscopic cholecystectomy in acute cholecystitis. Experiences with 20 cases]. AB - With the experience of 80 cases of laparoscopic cholecystectomy, we started to operate all gallbladders by the laparoscopic way, even if there was the diagnosis of an acute cholecystitis. Between May 1991 and January 1992, 20 patients with acute cholecystitis have been operated by laparoscopic surgery. The patients' ages varied from 21 to 75 years (mean 53 years). The preoperative evaluation of the biliferous ducts, especially in case of cholestasis, should give a precise diagnosis of anatomic variations or stones. Therefore the ERCP as an additional preoperative examination was necessary in 10 (50%) cases. 14 (70%) could be operated by the laparoscopic way without surgical complications. In 6 patients closed procedures had to be changed to open cholecystectomy because of the following reasons: Scars and uncertainty about the anatomy in Calot's triangle (4x), severe adhesions to the colon (1x), and perforation of a gallbladder with necrotic wall, respectively. The good results, the possibility of a direct view of the situs, and the fact that anytime during the operation a change to the open procedure is possible, are reasons to start all cholecystectomies by the laparoscopic manner. PMID- 8473175 TI - [Do pulmonary changes appear after elective laparoscopic cholecystectomy?]. AB - 30 patients without history of pulmonary disease who underwent elective laparoscopic cholecystectomy were examined on the day before and on the 2nd day after operation. Investigations included physical examination, chest X-ray and a spirometry. In case of postoperative pathological findings the same examinations were repeated 14 days after operation. On the chest X-ray 5 patients had postoperative alterations which disappeared within 14 days. The spirometry showed a slight decrease of VC, FRC and FEV1 which after 2 weeks had almost regained normal values. Therefore we do not consider it necessary to perform routine respiratory prophylaxis in patients undergoing elective laparoscopic cholecystectomy. PMID- 8473176 TI - [Stomach cancer: 10 years experiences with surgical treatment and possibilities for improving the prognosis]. AB - We retrospectively evaluated data on 111 consecutive patients operated between 1976 and 1985 for gastric carcinoma. Patients were staged according to the TNM classification (stage I - 17%, II - 15%, III - 30%, IV - 37%). 66 patients (59.5%) underwent radical resection. Most of curative resections were subtotal distal gastrectomies. Extended lymphadenectomy was not performed. The operative mortality rate was 7.4% in case of curative resections, and 9.6% overall. 20 out of 66 radically operated patients (30%) were treated with adjuvant cytotoxic chemotherapy, while 9 out of 45 non radically operated patients were treated with palliative cytotoxic chemotherapy. The median follow-up time was 36 months (range: 1-166 months) for patients operated for cure and 25 months for the whole population. The estimated adjusted 5-year survival rate was 41.3% after operation in a curative intent, 82.9% for stage I, 62.8% for stage II, 17.8% for stage III, 3.3% for stage IV. The duration of symptoms before diagnosis was longer than 6 months in 18 patients (16.2%) and longer than 10 months in 9 patients (8.1%). Patients who were symptomatic since more than 10 months were on the average about 10 years younger than the rest of the population. The median duration of symptoms was 3.2 months overall, but reached 7.1 months in patients less than 40 years old. Patients with an early gastric cancer (11/111: 9.9%) or stage I disease (19/111: 17.1%) had always symptoms since less than 5 months. The proportion of early gastric cancer increased from 6.3% (3/48) to 12.7% (8/63) from 1976-1980 to 1981-1985, simultaneously to the diffusion of the upper gastrointestinal endoscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473177 TI - [Value of antral mucosectomy, selective proximal vagotomy and a combination of the 2 procedures in serum gastrin production and inhibition of stomach acid. An experimental study]. AB - This experimental study was aimed at determining the volume and acidity produced by the normal stomach, following antral mucosectomy (MA), proximal selective vagotomy (VSP) and combination of both procedures. In 10 mongrel dogs, a double lumen tube was placed in the stomach under general anesthesia. One of the lumen was rinsed with a constant flow and the other retrieved the gastric secretion. Gastric secretion and acidity were calculated every 10 minutes for 120 minutes. At 60 minutes, pentagastrin was injected. After these controls, a MA was carried out in half the animals and a VSP in the other half. 6 and 12 weeks postoperatively, the same controls were repeated. The dogs were then submitted to the operation of the other group. Following MA and pentagastrin stimulation, the gastric secretion (volume) is not modified with regard to the preoperative levels. On the other hand, after VSP, pentagastrin stimulation induces only a small volume response. The vagus thus seems to be involved in liquid secretion of the stomach. Following MA, pentagastrin stimulation lowers gastric pH at 6 weeks but not at 12 weeks postoperatively. Gastrin is known to have a trophic effect on the oxyntic mucosa. This effect disappears in a few weeks and explains these different figures. Following VSP, gastric acidity decreases and plasmatic gastrin increases. In this situation, pentagastrin directly acts on a trophic mucosa and produces the important lowering of the gastric pH. Finally, after MA, pentagastrin induces an increase in plasmatic gastrin. This effect seems to be mediated by central stimulation of the nuclei of the vagus nerve. PMID- 8473178 TI - [Late results after individualized lateral internal sphincterotomy]. AB - A total of 75 patients underwent individualized lateral internal sphincterotomy for acute and chronic anal fissure (n = 30) or high pressure hemorrhoids (n = 45) and were followed-up 3 months and 3 years (13-66 months) postoperatively. All but one patient with anal fissure (97%) and 38 out of 45 patients with hemorrhoids (84%) remained symptom free; only one patient (1.3%) occasionally had symptoms of minor incontinence. Following the operation both the maximum resting pressure and the medium anal pressure fell significantly and were completely or nearly normalized in 54 (72%) and 17 (23%) patients respectively. At medium follow-up of 3 months and 3 years postoperatively there was no significant difference in the two sets of postoperative manometric results. PMID- 8473179 TI - [Colonic malrotation observed in the adult]. AB - Malrotation is a rare aetiological factor of intestinal occlusion in adult. We report our experience of 16 cases collected from 1976 to 1991. The incidence is about 0.2-0.5% with two peaks, at 25 and 55 years respectively. Mean age is of 41 years. The symptoms were occlusion in more than 90%. A contrast enema was performed in acute as well as in chronic situations. The surgical treatment whatever it is, is the treatment of choice but has to be put in balance with age. PMID- 8473180 TI - [Multiple tumors of the colon and rectum]. AB - The possible occurrence of multiple synchronous or metachronous malignant lesions in patients with a carcinoma of the colon and rectum is a well known event. In this population-based study in the Geneva area from 1970 to 1986, the frequency of synchronous colorectal carcinomas was of 1.1% and that of metachronous carcinomas of 1%. The relative risk of metachronous colorectal carcinoma is higher than in the general population (colon after rectum 1.2, colon after colon 1.7 and rectum after rectum 1.4). A high association of adenomatous polyps with multiple colorectal carcinomas was observed. The 5-year actuarial survival in case of curative resection was of 87% for metachronous carcinomas, 35% for single carcinomas and 33% for synchronous carcinomas. We conclude that complete preoperative colonoscopy, whenever possible, should be performed to screen patients with synchronous carcinomas. Finally, a lifelong follow-up of the residual colon or rectum should be planned to detect metachronous lesions. PMID- 8473182 TI - [Multi-organ procurement from the perspective of a hospital not involved in transplantation. Requirements, implementation, problems]. AB - Our algorithm is an example in which way the multiple organ donation can be organised in a hospital, which doesn't perform transplantations. We are showing problems which occur during the evaluation of the donor and till the explantation can be performed. In the conclusion we are demanding for better coordination and better support from the transplantation centers. PMID- 8473181 TI - [Thrombopenia after liver transplantation]. AB - Thrombocytopenia (TP) is a common finding after liver transplantation and is often multifactorially induced. In 31 of 33 liver transplant recipients (operated between 1986 and 1991 at our institution) TP was observed but only in 4 the nadir of the platelet count was less than 20,000/mm3. Highly significant influence in the severity of postoperative TP as well as on the recovery time (defined as the first day with a platelet count higher than 100,000/mm3) was found for a preexisting TP and for the intraoperative need for blood transfusions. 8/33 patients had a concomitant splenectomy but no effect on platelet nadir nor on the recovery time could be detected. In our series we could not find any platelet related factor with a significant impact on patient survival. In one patient severe TP was induced by a CMV-related hematophagic histiocytosis fully regredient with antiviral therapy. Another patient with AB0 incompatible graft had a severe TP induced by graft versus host disease. PMID- 8473183 TI - [Extracorporeal cholelithotripsy, is it still justified as treatment of cholecystolithiasis?]. AB - This prospective study evaluates the results of extracorporal shock-wave piezoelectric lithotripsy in 52 patients, 41 with radiolucent and 11 with calcified shell gallstones. The fragmentation rate was above 90% and the complication rate 31% particularly with pains or intolerance to the adjuvant dissolution therapy. At the end of the treatment, seven cholecystectomies were carried out among the 31 patients for who lithotripsy failed. After 18 months, the success rate was 23% and 12 patients only remained stone free. Nowadays, thanks to the new laparoscopic therapy, extracorporal shock-wave lithotripsy is no longer judged appropriate, especially because of its poor cost-effectiveness and high recurrence ratio. PMID- 8473184 TI - [Preoperative ERCP and laparoscopic cholecystectomy for treatment of choledocholithiasis]. AB - Out of 110 patients suffering from gallstone-related symptoms, 21 underwent ERCP prior to laparoscopic cholecystectomy. Indications for this combined treatment were laboratory signs of cholestasis (36%), pancreatitis (29%), pathological IVC (18%), sonographic evidence for bile duct dilatation (10%) and cholangitis (7%). Local and general complications were not increased neither intraoperatively nor postoperatively. Median duration of postoperative hospital stay was four days for ERCP-treated patients as compared to three days for patients subjected to laparoscopic cholecystectomy only. In summary treatment of choledocholithiasis by a combination of preoperative ERCP and laparoscopic cholecystectomy offers the following advantages: high patient comfort, low incidence of complications and short hospitalization compares favourably with conventional common bile duct exploration. PMID- 8473185 TI - [Polytrauma: comparison of the hospital course after air- (with emergency physician) versus ground transport (without emergency physician)]. AB - We analyzed the influence of initial intensive care at the accident site performed by an emergency physician and followed by helicopter transport on the course during hospital stay in patients with multiple trauma. We therefore compared the dates of 107 patients transported by the swiss air rescue (REGA) and an emergency physician with 131 patients transported by an ambulance and paramedic staff. By similar case material the REGA-patients showed a higher injury severity grade. Mortality of the REGA-patients was significantly higher (21%) than of the ambulance-patients (10%), but length of stay was significantly shorter and morbidity identical. We suspect, that the higher mortality of the REGA-patients is explained by the large number of surgically nontreatable severe traumas. None of the REGA-patients arrived at hospital with circulatory insufficiency whereas 4 of the ambulance-patients were in state of shock. We assume that first of all primary treatment of the scene of injury by an emergency physician and eventually also transport by helicopter have a positive effect on the course of patients with multiple trauma during hospital stay. PMID- 8473186 TI - [Unstable spinal injuries in craniocerebral trauma]. AB - Estimates of the incidence of injury to the cervical spine among patients suffering blunt trauma to the head vary widely. In an attempt to quantify the risk, the records of 593 consecutive patients with blunt craniocerebral injuries admitted to our trauma center in 1991 were reviewed. The overall incidence of cervical spine injuries was 5.8% and for the unstable cervical spine injuries 2.9%. In the management of head trauma with associated cervical spine injuries realignment and immobilisation of the spine and surgery of the head were carried out as first step, followed by decompression and stabilisation of the affected segment in the same session. In patients with altered consciousness a loss of cooperation is always present and an early spinal stabilisation for the optimal treatment in the intensive care unit and in the wake-up-phase is important. PMID- 8473188 TI - [Initial experiences with the unreamed AO tibial nail]. AB - It is generally accepted that intramedullary nailing in combination with reaming should be avoided in treating open fractures. However the use of an unreamed, solid nail combined with interlocking allows stabilization also of open and complex fractures. 20 tibia fractures (65% open, 45% complex fractures) have been treated by the AO unreamed tibial nail (UTN), 12 (5 of them open fractures) by direct nailing and 8 after initial stabilization by an external fixator. In our series no intraoperative complications, no soft-tissue healing problems and no infections occurred. Thus, treatment of both, open and comminuted fractures by UTN appears to be rather safe and generally needs no secondary stabilization. PMID- 8473187 TI - [Initial experiences with the unreamed tibial nail]. AB - During a one-year period starting January 1991, 17 tibial shaft fractures have been treated with the new AO unreamed tibial nail in a prospective study. Fractures were classified according to the AO classification: 10 type A, 6 type B, one type C. 7 fractures were closed. Out of those 3 showed marked soft tissue contusions and 2 required a fasciotomy because of a concomitant compartment syndrome. The open fractures were classified according to the Gustilo classification: 3 grade I, 5 grade II, 1 grade III B and 1 grade III C injury. There were 5 polytraumatised patients (ISS 27-34). The nailing procedure was preformed on the day of admission in 11 cases and in a delayed fashion (2-14 days after the accident) in 6 cases. There were no specific technical problems encountered intraoperatively. The only perioperative complication consisted of 1 case of fat embolism syndrome. 1 fracture required secondary plate osteosynthesis because of a unacceptable valgus deformity 6 weeks postoperatively. There was 1 too long nail implanted at the initial surgery, which then had to be changed during the rehabilitation period because of pain in the region of the knee. In 3 cases the interlocking bolts broke and 3 other cases required secondary dynamisation. There was a complete follow-up in all cases of at least 6 months. There were no infections. All fractures are healed. Full weight bearing was allowed at a mean of 10 weeks for closed fractures and 14 weeks for open fractures, respectively. All but one fracture (valgus 8 degrees) healed in a correct axial alignment without shortening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473189 TI - [Stable interlocking intramedullary nailing of humeral fractures with the Seidel nail]. AB - 22 fractures of the humerus (15 traumatological, 7 pathological) were treated with the Seidel-Nail. The results after a follow-up between 4 and 20 months showed good mobility of the shoulder. As major complications two paresis of the radial nerve occurred. One disappeared spontaneously. The Seidel-Nail is a good implant for all kind of shaft fractures with an intact distal fragment of 5 cm and also for fractures of an intact humerus head. PMID- 8473190 TI - [Osteosynthesis of subcapital humerus fracture with unconventionally applied implants]. AB - The osteosynthesis of proximal humerus fractures with the commonly used plates is often critical because of the small space subacromial, the irritation of the blood supply by the broad plates and the poor proximal anchorage without angle stability. The osteosynthesis with a children hip plate or a angle plate like modified DC-plate is thought to be a reliable alternative. PMID- 8473191 TI - [Results of intramedullary nailing in humerus shaft fractures]. AB - We present an analysis of a retrospective study of 61 humeral shaft fractures, stabilized with a thin AO tibial nail. All fractures were analysed according to the AO-classification. Follow-up included 48/61 patients and averaged 82 months. Local complications were postoperative radial nerve palsy in 1/61, infection in 0/61 and non-union in 4/56. A good result in shoulder function was obtained in 41/48 cases. PMID- 8473192 TI - [Preoperative arthroscopy in fresh complex internal knee injuries]. AB - With reference to a prospective study 197 preoperative arthroscopies were carried out on 194 patients with fresh severe internal lesions of the knee. The injuries are analysed, in particular diagnostic and treatment of additional meniscus lesions. Advantages and disadvantages of the procedure are discussed. PMID- 8473193 TI - [Arthroscopy in diagnosis of carpal instability]. AB - In a series of 45 patients with carpal instability, arthroscopy detected 2.9 ligament tears per wrist. The lesions were found in 50% in the radio-carpal compartment and in 50% in the midcarpal compartment on the ulnar aspect. In 70% the tears were found to be combined in both compartments. These findings may be in contrast to the today's classification of carpal instability. Arthroscopy is of great value in evaluating the most appropriate method of surgical repair on patients with carpal instability. PMID- 8473194 TI - [Results of surgical therapy of ulnar sulcus syndrome. Submuscular anterior transposition versus simple decompression of the ulnar nerve]. AB - The operative treatment of the ulnar neuropathy at the elbow is controversial. We studied the course of 79 patients who had been operated for the first time, either by simple decompression (31 cases) or by submuscular anterior transposition (48 cases) of the ulnar nerve. Our results show that the simple decompression can be recommended in all patients without cubital (sub)luxation of the ulnar nerve. The submuscular anterior transposition should be preferred if a tendency of cubital (sub)luxation of the ulnar nerve has been found. PMID- 8473195 TI - [Characteristics of tumor diseases in patients with colorectal cancer]. AB - Medical histories for the years 1978 to 1988 were reviewed to ascertain associations between colorectal cancers and extraintestinal malignancies. 61 out of 838 patients (7.3%) had an extraintestinal malignancy before the colorectal cancer. In males the rate was 5.4% and in females 10.4%. In males a high association was shown between cancers of the large bowel and urogenital cancers. In females colorectal cancer was associated with breast and gynecologic cancers. We conclude that patients with gynecologic and urologic tumors have an increased risk to develop cancers of the large bowel and that these high risk patients should undergo long-term follow-ups. PMID- 8473196 TI - [Complications of T-drainage after choledochotomy]. PMID- 8473198 TI - Estimating the initial reaction velocity of a soluble dehydrogenase in situ. AB - The initial reaction velocities (vi) of lactate dehydrogenase in single hepatocytes were determined, by microdensitometry or computer-assisted image analysis, in sections of unfixed mouse liver incubated at 37 degrees C on substrate-containing agarose gel films. They were found to fit the equations vi = 2.82 degrees A and vi = vi + 2 degrees A, where vi and degrees A are, respectively, the gradients (or steady-state linear velocities) and the intercepts on the absorbance axis of the linear regression lines of the absorbance (A) on incubation time plots for incubation times between 1 and 3 min. Both equations were independent of section thickness between 4 and 14 microns. The observed and calculated values of vi agreed within 11.5% (n = 71). The validity of the equations for vi was confirmed by showing that the calculated vi was proportional to the thickness of the section and hence the amount of enzyme present. Thus, vi can be determined from measurements of either degrees A alone or vi and degrees A. PMID- 8473197 TI - Spatial analysis of intranuclear human repetitive DNA regions by in situ hybridization and digital fluorescence microscopy. AB - Non-isotopic (fluorescent) in situ hybridization has established itself as a useful technique for the localization of DNA sequences in both metaphase and interphase cells. The rapid development of digital fluorescence microscopy, especially confocal microscopy, has become a powerful aid for the evaluation of the hybridization results in cytogenetic and cell biological applications. In this review we will demonstrate the utility of these methodologies for the three dimensional visualization and analysis of chromosome-specific (peri)centromeric repetitive DNA sequences within the intranuclear structure of human cells and cell lines. PMID- 8473199 TI - Kinetic analysis of lactate dehydrogenase in situ in mouse liver determined with a quantitative histochemical technique. AB - The kinetics of lactate dehydrogenase in situ were studied in sections of unfixed liver of the male mouse using a quantitative histochemical technique. The sections were incubated on substrate-containing gel films. The absorbance of the final reaction products deposited in a single hepatocyte was measured continuously during the incubation as a function of incubation time using a scanning microdensitometer. The absorbance increased non-linearly during the first minute of incubation, but linearly for at least the next 3 min afterwards. The initial velocity (vi) of the dehydrogenase was calculated from two equations proposed previously by us, vi = 2.82 degrees A and vi = vi + 2 degrees A, where vi and degrees A are, respectively, the gradient and intercept of the linear regression line of absorbance on time for incubation times between 1 and 3 min. The dependence of vi on lactate concentration gave the following mean kinetic constants. For periportal hepatocytes, the apparent Km = 14 mM and Vmax = 80 mumoles hydrogen equivalents formed cm-3 hepatocyte cytoplasm min-1. For pericentral hepatocytes, Km = 12 mM and Vmax = 87 mumoles hydrogen equivalents cm 3 min-1. The Km values are very similar to those determined previously from biochemical assays. The concentrations of the enzyme in single hepatocytes calculated from the Vmax values are in good agreement with those obtained by another method. These data substantiate the validity of our equations. PMID- 8473200 TI - Noradrenergic and acetylcholinesterase-positive nerve fibres of the uterus in sexually immature and cycling rats. AB - The distribution and density of the noradrenergic and acetylcholinesterase positive nerve fibres were histochemically studied in different uterine regions of prepubertal and cycling rats in dioestrus and oestrus. Besides the rich and double innervation of blood vessels, both types of nerve fibre were found in the myometrium and cervical musculature. The non-vascular noradrenergic network looked denser at the tubal end of the horns and at the cervix, whereas the acetylcholinesterase-positive innervation was poor at the tubal end, increasing toward the cervix. Contrasting with the middle third of the uterine horn, at the tubal end, the myometrial longitudinal layer was much more innervated than the circular one, especially by the noradrenergic nerve fibres. The prepubertal rats presented an adult pattern of uterine autonomic innervation. In the cycling animals, this innervation was nearly the same during oestrus and dioestrus regarding both the density of nerve fibres and intensity of the histochemical reactions. PMID- 8473201 TI - Tissue distribution of amyloid P component as defined by a monoclonal antibody produced by immunization with human glomerular basement membranes. AB - A monoclonal antibody reactive against amyloid P component (NCL-AMP) has been developed following immunization of mice with partially-purified human glomerular basement membranes (GBM) and standard hybridization and cloning techniques. The antibody reactivity was evaluated by enzyme-linked immunosorbent assay (ELISA) and by the indirect immunoperoxidase technique on sections of frozen and fixed human kidney and other tissues. The distribution of amyloid P component in various normal tissues is described and the possible co-localization with the Goodpasture antigen is discussed. In addition, the suitability of the antibody for detection of amyloid deposits in renal amyloidosis is demonstrated and its potential for use in other pathological conditions is considered. PMID- 8473202 TI - Semiquantitative immunohistochemical studies of blood group antigen A, B, H, Le(a), Le(b) structures and Ii backbone chains in the normal human cervix and in cervical adenocarcinoma. AB - Epithelia frequently express blood group antigens and these are often perturbed in neoplasia. This study has characterized the range of expression of ABH and Lewis terminal structures and the Ii backbone chains in the normal human cervix by semiquantitative immunohistochemistry. Effects of the secretor gene were defined by determination of salivary secretor status. Modifications of blood group antigen expression in cervical adenocarcinoma were also addressed. Normal cervical squamous and glandular epithelia showed a range of expression of the antigens studied. Lewis-gene-negative cases showed no expression of Lewis antigens. Secretor status had no effect on ABH expression in squamous epithelium, but it did have a marked effect on ABH expression in glands and on Le(b) expression in both squamous and glandular epithelia. Patterns of expression of i chains in squamous epithelium suggest that these may be the carriers of ABH and Lewis antigens in a proportion of cases. Distinct patterns of expression were seen in glandular tubal metaplasia and in endothelium. Adenocarcinomas showed topographical rather than quantitative changes in blood group antigen expression with more extensive luminal expression of ABH, Lewis and Ii structures than that seen in normal glands. This change is distinct from those usually associated with malignancy. PMID- 8473203 TI - [Regenerating hair cells. A therapy concept for the future?]. PMID- 8473204 TI - [Acceptance and hearing aid use by patients of retirement age (in the Magdeburg clinical area)]. AB - Providing patients with hearing aids in the former German Democratic Republic was carried out in audiological centers by otolaryngologists and authorized audiologic-phonatric assistants. The available selection of hearing aids was limited. A randomized group of 119 patients rehabilitated with hearing aids was examined. The current study includes persons older than 65 years. In 78.4% of the patients treated, the quality of life was improved with the hearing aids. In contrast, the other patients reported the aids to be useless. Nearly 90% of all patients had no problems in managing their hearing aids. About 75% of the patients used the hearing aid the whole day. In addition to the hearing aid prescribed, 33 patients also have had to read lips and only a combination of both allows these patients to have adequate communication. Patients reported that 80% of the hearing aids worked well or were rarely out of order. Further, 68% of the people questioned reported a positive attitude of their fellow citizens. Only 6% mentioned that the use of hearing aids to treat presbycusis disturbed social communications. Since hearing loss can be progressive and to avoid interference in early rehabilitation, frequent follow-ups by otorhinolaryngologists are required. The evaluation of patients with hearing disorders requires the collaboration of physicians and hearing aid acousticians in order to give patients the most information and understanding of their deafness. PMID- 8473205 TI - [3D endoscopy]. AB - With the aid of a 6 mm 0 degree stereo-endoscope supplied with a 100 Hz monitor and high-speed liquid crystal shutter, three-dimensional endoscopy of the upper airway was realized for the first time. The equipment used is based on alternating sequential projections of left and right eye images on a single tv screen. Two high-speed liquid crystal stereo switches (LCSS) are integrated in glasses and a rapid switching time of 100 microseconds is used. In a comparative study this innovative endoscopic technique was tested for its practicability in sinus surgery and endoscopy of the upper airway. With this equipment an excellent view was obtained of the pharynx, larynx and trachea. For sinus surgery, however, a stereoendoscope with smaller dimensions has to be developed. PMID- 8473206 TI - [Prevention of vascular complications in endonasal paranasal sinus surgery. I: Anatomic principles and surgical significance]. AB - Anatomic and histologic investigations were performed in 59 cadaver half-heads in order to demonstrate areas of hazard at the posterior skull base during endoscopic surgery and determine morphologic features of surgical relevance. In 78% of the heads the internal carotid artery bulged into the sphenoid sinus from laterally directly behind and beyond the tuberculum for the optic nerve ("anterior bulging"). In 25% of all cases the carotid artery also bulged into the sphenoid sinus from behind ("posterior bulging"). This bulging could amount to as much as 7 mm. Additionally, the thickness of the bony wall at the point of the largest prominence could be very thin (0.1 mm), with 12% of all cases showing bony dehiscences. The width of the posterior ethmoid cells and pneumatization of the paranasal sinuses at this point differed widely, ranging from 8-24 mm. Classification of the carotid loop into five different types demonstrated that the bulgings of the internal carotid artery were larger in more curved types of the artery ("omega" and "U" types) and were smaller in less curved types ("Arkus" and "V" types). PMID- 8473207 TI - [The physician and accidents. Legal and medical problems]. AB - German law requires that any physician at a place of accident is obliged to help according to his training and ability. As an emergency doctor on duty he works in a warrantee position. In cases with multiple accident victims triage may be necessary, corresponding to the priority of medical care. In criminal procedures against a physician due to omitted help, there is no probative charge against the accused. On the other hand, civil law sets up an objective standard: attention as required in communication. In giving initial medical assistance for unconscious patients or injured children, rules of "authorized management without commission" become valid. Basic first aid measures involve: securing, saving and rescue. Life threatening situations such as severe bleeding, airway obstruction and cardiac arrest must be dealt with immediately. Following this, such measures as proper positioning, clearing of the respiratory tract, removal of dental prostheses, evaluation of multiple injuries, avoidance of hypothermia and initiating infusions are mandatory. The orientating examination of the accident victim is described, as is the "ABCD Rule" for treating respiratory insufficiency or circulatory arrest and shock, using heart massage and artificial respiration. Finally, medical first aid is described for special injuries, such as cerebral or thoracic trauma, fractures and burns. The psychological situation affecting the physician at the place of an accident is characterized. PMID- 8473208 TI - Opposes early-age neutering. PMID- 8473209 TI - Fluid therapy for smoke and fire injury. PMID- 8473210 TI - Nasopharyngeal foreign body. PMID- 8473211 TI - Escherichia coli O157:H7 infection forces awareness of food production and handling. PMID- 8473212 TI - AAFCO serves up new regulations to pet food industry. PMID- 8473213 TI - AVMA legislation: partial solution to drug availability problem. PMID- 8473214 TI - Trinidad veterinarian. PMID- 8473215 TI - Negligence in diagnosis. PMID- 8473216 TI - Frequency of procedure and proficiency expected of new veterinary school graduates with regard to small animal surgical procedures in private practice. PMID- 8473217 TI - Conservation and wildlife preservation challenges for veterinarians. PMID- 8473218 TI - Wildlife health and the urban-wildlife interface. PMID- 8473219 TI - Relationships of agricultural and economic policy to the health of farm families, livestock, and the environment. PMID- 8473220 TI - Environmental disasters and veterinarians' response. PMID- 8473221 TI - The environment and regulatory impacts. PMID- 8473222 TI - Effect of subclinical infection with Actinobacillus pleuropneumoniae in commingled feeder swine. AB - Sequential serologic analysis for Actinobacillus pleuropneumoniae was done on 240 commingled feeder swine at 1 and 21 days after purchase and at slaughter. At the beginning of the experiment, mean weight of the pigs was 18.6 kg, and the pigs were maintained to a mean slaughter weight of 109.95 kg. A fourfold increase in antibody titer against Actinobacillus pleuropneumoniae was demonstrated in 28 (12%) pigs. Mean adjusted rate of gain for infected pigs was 0.74 +/- 0.10 kg/d and 0.77 +/- 0.09 kg/d for uninfected pigs. Differences in feed efficiency were not detected between infected and uninfected pigs. Our findings suggested that 5.64 additional days are required for pigs with subclinical infection to reach market weight of 113.6 kg, compared with that for uninfected herdmates. A vaccination program to prevent subclinical infection may not be cost effective. PMID- 8473223 TI - Pathologic correlations with magnetic resonance images of osteochondrosis lesions in canine shoulders. AB - Twelve shoulders in 6 dogs with clinical and radiographic evidence of osteochondrosis were examined by magnetic resonance imaging performed on a 0.5-T superconductive system. Scans were obtained with 5-mm-thick slices and 0.75-mm pixel size. Unenhanced T1-weighted spin-echo and unenhanced T2*-weighted gradient echo images were obtained, using a high-resolution surface coil. The T1-weighted sequences were repeated after IV injection of 0.1 mmol of gadopentetate dimeglumine/kg of body weight (0.2 ml/kg). In 6 joints, histologic examination of synovia and articular cartilage was carried out. The magnetic resonance images were correlated with arthrographic, arthroscopic, and histologic findings. Magnetic resonance imaging was useful in evaluating the extent of subchondral lesions and the severity of inflammatory changes within the subchondral bone. Areas of low signal (visible subchondrally on T1-weighted images that were enhanced by administration of contrast medium) indicated active inflammatory changes within the subchondral bone. Although articular cartilage discontinuity could be detected, loose cartilage flaps could not always be reliably demonstrated. Signal inhomogeneity within the articular cartilage was presumed to correspond with zones of cartilage degeneration. PMID- 8473224 TI - Comparison of computed tomography with radiography as a noninvasive diagnostic technique for chronic nasal disease in dogs. AB - Computed tomography was evaluated as a noninvasive technique for the diagnosis of chronic nasal disease in dogs. Computed tomographic images, radiographs, and histopathologic findings were compared in 11 dogs with chronic nasal disease. Definitive diagnosis was made following traumatic nasal flush, exploratory surgery, or necropsy. The study included 8 dogs with intranasal tumors, 2 dogs with bacterial rhinitis (Pasteurella sp), and 1 dog with mycotic rhinitis (Aspergillus sp). Computed tomography was superior to radiography in defining the extent of the disease process and in differentiating infectious rhinitis from nasal neoplasms. It defined lesions in the palate, nasopharyngeal meatus, maxillary sinus, caudal ethmoturbinates, and periorbital tissues that were difficult to demonstrate by use of conventional radiography. Tumors appeared as space-occupying lesions that obliterated the turbinates, caused deviation of the nasal septum, and eroded bone. Rhinitis appeared as a cavitating lesion that spared the paranasal sinuses, thickened and distorted the turbinates, and widened the meatus. Although morphologically distinct on computed tomographic images, infectious rhinitis and nasal neoplasms could not be differentiated by attenuation measurements or degree of contrast enhancement. Computed tomography appeared to be a reliable, noninvasive technique for the diagnosis of chronic nasal disease in dogs, and a promising alternative to diagnostic techniques currently in use. PMID- 8473225 TI - Adverse effects of administration of propofol with various preanesthetic regimens in dogs. AB - The effects of propofol on anesthetic induction were evaluated in 40 dogs anesthetized with isoflurane. Propofol is a rapidly acting, nonbarbiturate drug that induces anesthesia of ultrashort duration with IV administration. Four preanesthetic regimens were used: anesthesia without preanesthetic drugs; or with preanesthetic administration of acepromazine (0.1 mg/kg of body weight, IM), diazepam (0.2 mg/kg, IV), or acepromazine (0.02 mg/kg) and butorphanol (0.4 mg/kg) IM. Heart rate, systolic arterial blood pressure (SAP), respiration, quality of induction and recovery, and adverse effects were induction and recovery, and adverse effects were recorded. Intravenous propofol administration induced a variable period of apnea in 34 of 40 dogs. Cyanosis (in 2 dogs) and signs of pain on injection (in 3 dogs) were infrequently observed during induction. One dog developed ventricular premature depolarizations after propofol administration. Venous CO2 tension increased and pH decreased immediately after propofol administration, regardless of preanesthetic regimen. The SAP significantly (P < 0.05) decreased after propofol administration in dogs treated with acepromazine (SAP, 178 mm of Hg before vs 128 mm of Hg after propofol) and with acepromazine/butorphanol (SAP, 184 mm of Hg before vs 98 mm of Hg after propofol). When used for induction, propofol induces anesthetic-related adverse effects, some of which can be minimized by preanesthetic medication. Recovery characteristics varied with preanesthetic medication, independent of propofol administration. PMID- 8473226 TI - Pulmonary edema associated with transient airway obstruction in three horses. AB - Pulmonary edema associated with transient airway obstruction was detected in 3 horses. The cause of obstruction was different in each horse, but after relief of the obstruction, clinical signs and radiographic abnormalities were indicative of pulmonary edema. In 2 of the 3 horses, pink frothy fluid was evident in the airways. The horses were treated with furosemide, nasal insufflation of O2, anti inflammatory agents, and anti-biotics. Of the 3 horses examined, 1 horse died acutely, 1 horse recovered fully, and 1 developed pleuritis and was subsequently euthanatized. PMID- 8473227 TI - Use of a modified Roux-en-Y procedure for treatment of pyloroduodenal obstruction in a horse. AB - A modification of the Roux-en-Y anastomosis procedure was used to bypass a pyloroduodenal mass in a 12-year-old Arabian stallion. Clinical signs had consisted of a 4-week progression of ventral and hind limb edema, hypoproteinemia, fecal occult blood, intermittent abdominal pain, weight loss, and gastric reflux. On exploratory celiotomy, an obstructive mass was found in the pylorus and proximal portion of the duodenum. Gastrojejunostomy and duodenojejunostomy were performed by use of stapled side-to-side anastomosis techniques. Inaccessibility of the obstructed pyloric region prevented resection of the affected area. PMID- 8473228 TI - Repair of sacral fracture in two dairy cattle. AB - Sacral fractures in 2 dairy cattle were repaired surgically for cosmetic reasons. A heifer had a Salter-Harris type-I fracture of the fifth sacral vertebra, which was repaired with a 4.5-mm narrow dynamic compression plate. A cow had complete fracture of the fourth sacral body, which was repaired with 2 extra-large plastic spinous process plates. Both fixations were successful in restoring the dorsal contour of the sacrococcygeal region. PMID- 8473229 TI - Hemorrhage into the guttural pouch (auditory tube diverticulum) associated with rupture of the longus capitis muscle in three horses. AB - Three horses were determined to have hemorrhage into a guttural pouch unassociated with mycosis, empyema, neoplasia, or foreign body. The source of the hemorrhage appeared to be the rupture of the longus capitis muscle and its associated vascular supply. PMID- 8473230 TI - Primary parathyroid gland hyperplasia in dogs: six cases (1982-1991). AB - Persistent hypercalcemia attributable to parathyroid gland hyperplasia was identified in 6 dogs with primary hyperparathyroidism. Clinical signs included polydipsia (n = 4), polyuria (n = 4), and signs caused by cystic calculi (n = 3). Abnormal clinical pathologic findings included hypercalcemia (mean, 13.6 mg/dl; range, 12.6 to 14.7 mg/dl; n = 6), hypophosphatemia (mean, 2.2 mg/dl; range, 1.4 to 2.9 mg/dl; n = 6), high serum alkaline phosphatase activity (mean, 222 IU/L; range, 161 to 286 IU/L; n = 3), and isosthenuria (mean, 1.012; range, 1.006 to 1.017; n = 6). Serum parathyroid hormone concentration was within the reference range or high (mean, 23 pmol/L; range, 7 to 119 pmol/L; reference range, 1.5 to 13 pmol/L) in all dogs. At surgery, the number of large parathyroid glands was variable, being limited to 1 gland in 3 dogs, 2 glands in 2 dogs, and 4 glands in 1 dog. All visibly large parathyroid glands were surgically removed from each dog. Serum calcium concentration decreased into or below the reference range within 72 hours of surgery in all dogs, confirming the diagnosis of primary parathyroid disease. Multiple nodules of adenomatous hyperplasia were identified in each dog. All 6 dogs were treated with vitamin D and calcium carbonate following surgery. The dog from which all 4 parathyroid glands were removed has remained eucalcemic for more than 1 year with vitamin D supplementation. Vitamin D and calcium administration was discontinued within 4 to 12 weeks of surgery in the remaining 5 dogs. These dogs remained eucalcemic without vitamin D supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473231 TI - Cholelithiasis in dogs: 29 cases (1980-1990). AB - Medical records of 29 dogs with cholelithiasis were reviewed. Aged female small breed dogs were overrepresented. Mean age was 9.5 years, and mean weight was 12 kg. Vomiting, anorexia, weakness, polyuria/polydipsia, weight loss, icterus, fever, and signs of abdominal pain were the most common clinical signs. Leukocytosis, neutrophilia with left shift, monocytosis, high activity of serum hepatic enzymes, hypoalbuminemia, and high concentrations of serum total bilirubin were common. Radiopaque choleliths were evident on abdominal radiography of 13 of 27 dogs. Microbial culturing of bile isolated organisms in 15 of 20 dogs. Gram-negative bacteria were most common. Surgery was performed in 22 dogs. Four dogs were treated medically, and 3 dogs were euthanatized without treatment. Surgical treatment consisted of cholecystectomy in 11 dogs, choledochotomy in 5 dogs, cholecystotomy in 4 dogs, and cholecystojejunostomy in 1 dog. Sphincter of Oddiotomy was performed in 1 dog. Five dogs had concurrent generalized peritonitis attributable to bile. Multiple choleliths were detected in most of the dogs. Choleliths were located in the gallbladder in 20 dogs and in the bile ducts in 14 dogs. The most common abnormalities of the gallbladder, identified histologically, were chronic cholecystitis, mucosal hyperplasia, and pericholecystic inflammation. The most common abnormalities of the liver were cholestasis, hepatocellular degeneration, and periportal fibrosis. Survival rate of dogs that underwent cholecystectomy tended to be higher (86%) than that of dogs treated via cholecystotomy (50%) or cholecystectomy in combination with choledochotomy (33%). Dogs that underwent medical treatment, abdominal exploratory, cholecystojenunostomy, choledochotomy, and sphincter of Oddiotomy died or were euthanatized because of redevelopment of clinical signs associated with cholelithiasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473232 TI - What is your diagnosis? Avulsion of the urethra from the urinary bladder. PMID- 8473233 TI - Decreased responsiveness to progesterone of spermatozoa in oligozoospermic patients. AB - Spermatozoa from oligozoospermic subjects are characterized by a reduced in vitro ability to penetrate hamster oocytes and by a decreased responsiveness to physiological stimuli that trigger the acrosome reaction. One of the first steps in the induction of the acrosome reaction is an increase of intracellular free calcium concentrations ([Ca2+]i). It has been recently shown that progesterone (P) is able to increase [Ca2+]i in capacitated human sperm at concentrations similar to those found in follicular fluid. We evaluated sperm [Ca2+]i increase in response to P (0.1 micrograms/ml) in 19 normo- and 17 oligozoospermic subjects. The average percentage of [Ca2+]i increase over the basal level was significantly lower in spermatozoa from oligozoospermic subjects when compared to normozoospermic subjects (138.7 +/- 8.22% increase in oligo- versus 263.3 +/- 39.7% increase in normozoospermic subjects; P < 0.001). Progesterone-stimulated [Ca2+]i increase was significantly correlated with sperm motility (r = 0.54), sperm concentration (r = 0.96), and sperm morphology (% of normal forms) (r = 0.49). In addition P induced a significant increase of acrosome-reacted spermatozoa in normospermic patients (n = 10), whereas no significant effect was observed in spermatozoa from oligozoospermic men (n = 7). Taken together, these results indicate that spermatozoa from oligozoospermic men have a reduced ability to initiate the cascade of events that lead to the acrosome reaction in response to a physiological stimulus, such as P, and might contribute to explaining the reduced fertilizing capacity of these patients. PMID- 8473234 TI - Androgen UDP-glucuronyl transferase activity is found primarily in liver in the rat. AB - UDP-glucuronyl transferase (UDPGT) activity was determined for androgens in tissue minces and microsomal fractions from the liver and extrahepatic tissues (kidney, skin, prostate, and preputial glands) of the male rat. Liver microsomes showed the highest UDPGT activity with each of the androgens tested (Vmax = 7, 3, and 10 nmol/minute/mg protein for testosterone, androsterone, and androstanediol, respectively). UDPGT activity (Vmax) for androstanediol in the liver was 10(2) fold higher than in the kidney and 10(3)-fold higher than in the skin and prostate. UDPGT activity for androgens was not detected in microsomes from preputial glands. Furthermore, no body site distribution was found for androgen UDPGT activity in skin microsomes. The Michaelis-Menten constant (Km) for UDPGT in liver microsomes was 20.4, 12.2, and 2.2 microM, respectively, for testosterone, androstanediol, and androsterone. Kidney microsomes showed a Km of 19.4 and 26.9 microM, respectively, for androstanediol and androsterone. The Km for testosterone was very high in the kidney (138 microM), suggesting that it was a poor substrate. In microsomes from the skin and prostate, the Km was very high (range 43-162 microM) for all three androgen substrates, suggesting that these androgens were not the preferred substrates for UDPGT in these tissues. These results indicate that the liver was the main site of androgen UDPGT activity and the skin and prostate formed little, if any, androgen glucuronides. These results suggest that androstanediol glucuronide was formed primarily in the liver and may not be a reliable marker of peripheral androgen metabolism. PMID- 8473235 TI - Immunocytochemical localization of the Yf subunit of glutathione S-transferase P shows regional variation in the staining of epithelial cells of the testis, efferent ducts, and epididymis of the male rat. AB - Glutathione S-transferases (GSTs) are a family of isozymes that catalyze the conjugation of glutathione (GSH), a tripeptide found in all mammalian cells; this function plays a protective role, as the addition of GSH to an electrophile generally forms a less toxic product. The pi class of GSTs contains homodimers of the Yf subunit, also known as Yp or rat subunit 7; this subunit is found in high concentrations in the testis and epididymis. The objective of the present study was to localize immunocytochemically the Yf subunit in the testis and in the various regions of the epididymis using light, electron, and confocal microscopy. In the testis, immunoperoxidase staining was localized exclusively to Sertoli and Leydig cells. The low cuboidal epithelial cells of the rete testis and the sparse ciliated cells of the ductuli efferents were also immunoreactive. A distinct pattern of immunostaining for the Yf subunit was observed in the different regions of the epididymis. The proximal area of the initial segment showed intense reactivity localized to epithelial basal cells. Basal cells in the middle area of the initial segment were also reactive, as were a second unidentified population of cells located in the apical region of the epithelium. The epithelium, including both principal and basal cells, in the distal initial segment, intermediate zone, and proximal caput epididymidis showed a weak, moderate, or strong degree of reactivity, respectively. In the distal caput epididymidis, however, principal cells showed a checkerboard-like pattern of immunoreactivity, with some cells being intensely stained or faintly stained, whereas others were unreactive. Strikingly, in the corpus and proximal cauda epididymidis, intense immunostaining was localized exclusively over the epithelial basal cells. As viewed in the light and confocal microscope, the intensely stained basal cells showed extensive processes that covered most of the base of the epididymal tubule. Upon quantitation of the immunogold labeling density (the number of gold particles/microns2) in principal and basal cells of the different regions of the epididymis, we observed a sharp decline in immunogold labeling of principal cells coupled with a dramatic increase in labeling of basal cells as we progressed along the tissue, particularly in the transition from the caput to the corpus epididymidis. This study constitutes the first demonstration of a protein that is selectively expressed in epithelial basal cells of the corpus and proximal cauda epididymidis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8473236 TI - Pharmacokinetics and pharmacodynamics of a parenteral testosterone microsphere formulation in the male rat. Demonstration of dose dependence and controlled release. AB - This study examined the pharmacokinetics (the time course and pattern of testosterone release) and pharmacodynamics (effects on accessory sex organ weights, and serum LH and FSH levels) of a biodegradable testosterone microsphere formulation in the male rat. Two hundred seventy-five 55-day-old, sexually mature male rats underwent surgical orchiectomy or sham surgery and were divided into five groups as follows, to receive placebo or testosterone microsphere systems designed to release 25, 75, or 225 micrograms/day testosterone: group I: intact age-matched controls, sham operated, placebo microspheres; group II: surgically orchiectomized, placebo microspheres; group III: surgically orchiectomized, 25 micrograms/day testosterone microspheres; group IV: surgically orchiectomized, 75 micrograms/day testosterone microspheres; and group V: surgically orchiectomized, 225 micrograms/day testosterone microspheres. Serum testosterone levels were fairly uniform from day 2 to 85 without any significant trend. After day 100, serum testosterone levels gradually fell into the castrate range by day 196. There was a dose-dependent increase in serum testosterone levels in groups III, IV, and V over those seen in group II (castrated rats, placebo treated). Prostate and seminal vesicle weights were significantly lower in castrated animals treated with placebo or the 25-micrograms/day testosterone microsphere system (group III). Mean prostate and seminal vesicle weights in groups IV and V were not significantly different from those in intact controls (group I) in the first 85 days. After day 85-100, seminal vesicle and prostate weights declined gradually in groups III, IV, and V, approaching castrate range by day 196.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473237 TI - Importance of total motile oval count in interpreting the hamster ovum sperm penetration assay. AB - A prospective study relating computer-assisted semen analysis (CASA) and technician-determined morphology to sperm penetration assay (SPA) outcome in patients with unexplained infertility or male factor was undertaken on 190 males aged 28-45 to determine the value of total motile oval count (TMO), compared to concentration, motility, and morphology considered independently, in predicting the outcome of the SPA. Prewash sperm count ranged 20-1,328 x 10(6), motility 0 93%, morphology 25-78% oval (%OVAL), and SPA scores 0-100%. Multiple regression analysis yielded two statistical models that identified significant predictors for % penetration (%P). Only TMO in one model and %OVAL in an independent effects model showed statistically significant correlation (P < 0.0001) to %P for all subjects. Discriminant function analysis showed the TMO model 85.4% accurate in classifying %P both in the abnormal range (< 20%P) and in the normal range (> or = 20%P). The independent effects model correctly classified 93% in the abnormal group, but projected 72 false negatives in the 101 subjects with %P > or = 20%, correctly classifying only 28.7%. Relative risk analysis showed TMO as a stronger risk factor affecting SPA outcome than %OVAL. It is concluded from this study that below 20%P, both TMO and %OVAL appeared to be comparable as predictive factors. Additionally, the TMO model was equally predictive for SPA > or = 20%P, where the independent effects model showed only 28.7% accuracy. SPA outcome appeared to be more profoundly affected by a decrease in TMO than by a decrease in %OVAL alone. PMID- 8473238 TI - Computer-assisted semen analysis (CASA) of epididymal sperm from the domestic cat. AB - Motion characteristics of epididymal sperm from domestic cats exhibiting a high (> 60%; normozoospermic; n = 21) or low (< 40%; teratozoospermic; n = 6) occurrence of structurally normal spermatozoa were correlated with morphology (MOR) using computer-assisted semen analysis (CASA). Mean values and standard errors for percent motility (MOT), curvilinear velocity (VCL), linearity (LIN), straight line velocity (VSL), and amplitude of lateral head displacement (ALH) were recorded for 3 hours. Average values for percent normal spermatozoa, MOT, VCL, VSL, and ALH were higher (P < 0.01) in samples from normozoospermic cats than from teratozoospermic cats at 0 hours, and there was no difference in motion parameters over the 3-hour incubation period in either group. Strong correlations (P < 0.01) existed between MOR and VCL, VSL, ALH, or MOT, but not LIN, upon regression analysis. We conclude that (1) motion parameters of domestic cat sperm are significantly correlated with morphology and (2) abnormal motion parameters associated with low fertility potential in other species are prevalent in samples from teratozoospermic cats. The correlation between morphology and altered sperm movement found in this study suggests that motion analysis of spermatozoa by CASA may be useful in evaluating fertilization potential in felids. PMID- 8473239 TI - Effect of catheter composition on sperm quality. AB - Bladder catheterization for collection of retrograde ejaculates is commonly practiced, although previous studies have shown that materials used in the manufacture of the catheters may be toxic to sperm. Potential toxicity is particularly relevant to electroejaculation, as sperm from anejaculatory individuals undergoing this procedure characteristically exhibit poor motility and viability. To determine the effect of short-term exposure to various catheter materials on sperm quality, donor semen was diluted with BWW medium and aliquots incubated for 1 and 5 minutes with segments of four different catheters. The catheters were composed of latex, silicone rubber, polytetrafluoroethylene (Teflon), and radio-opaque Teflon, respectively. Following incubation, eosin nigrosin staining for viability was performed and sperm motility assessed using computer-assisted sperm analysis (Cellsoft, Cryo Resources, Ltd). In the second phase of the study, donor semen was incubated with catheter segments coated with 0.3 ml of a water-soluble, nontoxic lubricant (Cellulosagel, Lederle) to evaluate whether the combination adversely affects sperm. Percent motility and viability for the semen specimens incubated with the four catheters alone did not differ significantly from control values either at 1 or at 5 minutes (P = 0.3, motility; P = 0.6, viability). The addition of lubricant did not change the catheter data significantly, indicating the absence of independent or synergistic toxicity (P = 0.5, motility; P = 0.4, viability). This study provides substantial evidence that brief exposure to conventional catheters, with or without a nontoxic lubricant, does not adversely affect sperm motility or viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473240 TI - Hormonal modulation of the interactions of cultured rat testicular Sertoli and peritubular myoid cells. Effects on glycosaminoglycan synthesis. AB - Previous investigators have suggested metabolic cooperation between Sertoli and peritubular cells. This study concerns Sertoli cell and peritubular myoid cell interactions in terms of synthesis of one of the main testicular extracellular matrix (ECM) constituents, glycosaminoglycans (GAG). We have tested the effect of hormones and other regulatory agents such as a combination of FSH, insulin, retinol, and testosterone (FIRT) on monocultures of Sertoli and peritubular myoid cells, and have examined whether or not coculture of Sertoli and peritubular myoid cells substitutes for the stimulation by FIRT. Cocultures of Sertoli and testicular peritubular myoid cells showed significant increases in the levels of secreted protein and sulfoprotein, as well as in cell-associated GAG synthesis in untreated cultures. This indicates cell-cell cooperation between Sertoli and peritubular myoid cells in the testis in terms of sulfated protein and GAG synthesis. Addition of the hormone mixture and retinol (FIRT) stimulated cell associated and ECM-associated GAG in peritubular myoid cells, suggesting a role of circulating hormones in ECM production by peritubular myoid cells in vivo. Cocultures of Sertoli and myoid cells substituted for the stimulatory response of FIRT on peritubular myoid cells, predominantly in terms of cell-associated GAG synthesis, which again emphasizes that the paracrine regulation of testicular ECM synthesis is dependent on Sertoli-myoid cell cooperation. PMID- 8473241 TI - Sleep and active cochlear micromechanical properties in human subjects. AB - In this paper the effect of sleep on the cochlea is studied by transiently evoked otoacoustic emissions (TEOAEs). Amplitude increases considerably (e.g., 4 dB) and the effect of a contralateral noise on the TEOAEs decreases during the night. These modifications can be related to sleep, although there is no link to electroencephalographic sleep stage. During sleep onset, the effect of contralateral noise disappears: this could correspond to a functional rest of the auditory pathway during that period. PMID- 8473242 TI - Electrical stimulation of the auditory nerve: the effect of electrode position on neural excitation. AB - Histological studies have shown that the Melbourne/Cochlear electrode array lies along the outer wall of the scala tympani and is therefore some distance from the residual VIIIth nerve elements. In order to investigate the influence of electrode position on neural excitation we systematically varied the position of the electrode array within the cat scala tympani while recording electrically evoked auditory brainstem responses (EABRs). Using both normal hearing and long term deafened animals, we observed significant reductions in EABR thresholds as the electrode array was moved from the outer wall towards the modiolus. Further threshold reductions were observed when the array was placed underneath the osseous spiral lamina (OSL) close to the peripheral dendrites. These changes were independent of the bipolar inter-electrode separation, and were observed over a wide range of cochlear pathologies varying from normal to a moderate spiral ganglion cell loss. Interestingly, the one animal exhibiting extensive neural loss showed no correlation between EABR threshold and electrode position. There was also a general decrease in the gradient of the EABR input-output function as the electrode array was moved closer to the neural elements. This was, however, only statistically significant when the electrode was positioned adjacent to the peripheral dendrites. Significant reductions in EABR threshold were also observed as the inter-electrode spacing of the bipolar electrodes was increased. The gradient of the EABR input-output function also increased with increasing inter electrode spacing, although again, this was only significant when the electrode array was positioned close to the neural elements. The present results indicate that the optimum placement of a Melbourne/Cochlear electrode array is adjacent to the peripheral dendrites. However, such a site would be difficult to achieve in practice while minimizing insertion trauma. An array lying adjacent to the modiolus would be a safe alternative while ensuring a significant reduction in threshold compared with the existing site (outer wall). This placement should result in more localized neural excitation patterns, an increase in the number of bipolar electrodes available, together with an increase in their dynamic range. These changes may lead to further improvements in speech perception among cochlear implant patients. PMID- 8473243 TI - Incorporation of D3H glucosamine to the adult and developing cochlear tectorial membrane of normal and hypothyroid rats. AB - The uptake of D-3H-glucosamine by the developing cochlea of normal and hypothyroid rats was examined using light microscopic radioautography. During postnatal development, normal and hypothyroid rat cochleas exhibited a layer of radiolabelling in the tectorial membrane (TM). This layer first appeared in the TM region which covers the spiral limbus and the Kolliker's organ (KO), then progressively reached the apical part of the TM covering the organ of Corti. Radiolabelling was significantly greater in hypothyroid than in normal cochleas. These findings suggests that the enormous size reached by the TM in the congenital hypothyroidism could be related to an increase of epithelial secretion, at least for carbohydrates. It also suggests that TM, in normal and hypothyroid cochleas, could be formed during development by the addition of successive layers. Older layers could be displaced upwards by the new ones. Cochleas of normal young adult rats, treated with D-3H-glucosamine, showed a very scarce and diffuse radiolabelling. Cochleas of hypothyroid young adult rats exhibited a thickened and distorted TM, which incorporated a significant amount of carbohydrates. These results suggest that TM secretion is highly reduced in young adult normal animals, while in young adult hypothyroid ones it is still active. During cochlear maturation, thyroxine seems to be necessary, not only for the synthesis of normal glycoproteins (as suggested by previous reports), but also for the control of glycoprotein secretion. PMID- 8473244 TI - Two-tone suppression and distortion production on the basilar membrane in the hook region of cat and guinea pig cochleae. AB - Two-tone suppression and two-tone distortion were investigated at the level of the basilar membrane in the hook region of cat and guinea pig cochleae using a displacement-sensitive laser interferometric measurement system. The system allowed measurements to be performed at physiological stimulus levels in the cochlear region tuned to 30-35 kHz in cat and 29 kHz in guinea pig. The amplitude of vibration of the basilar membrane due to a probe tone at the characteristic frequency (CF) was attenuated during the presentation of a simultaneous suppressor tone either above or below CF. The amount of suppression depended on the intensities of both probe and suppressor, and the relationship of the suppressor frequency to the CF. Suppressors at frequencies more than an octave below the CF attenuated the responses to the CF probe at a rate of up to 1 dB/dB, with little variation based on suppressor frequency. As the suppressor frequency was increased above CF the rate of suppression decreased rapidly. The lowest suppressor intensity at which attenuation of the probe response was observed did not vary in direct proportion to the probe intensity. This suppression threshold often varied only a few dB SPL when the probe was varied over a 20 dB SPL range. In a few instances the rate of attenuation was as much as a factor of two greater at the lowest probe intensities than at higher intensities. It is noteworthy that suppression was found when the frequency of the suppressor was either above or below CF in the same preparation. Low frequency suppressor tones suppress basilar membrane motion at the CF when the basilar membrane undergoes displacement toward either scala. The maximum suppression occurs around 100 microseconds after the peak excursions caused by the low frequency biasing tone. Two-tone distortion products were often observed even at stimulus levels below those causing two-tone suppression at the site studied. The cubic difference tone (CDT) was the most prominent of the distortion products. The level of the CDT component varied nonmonotonically with the level of either of the primary tones. Responses at the difference frequency between the two primaries were usually below the noise floor of the recording system. The existence of both two-tone distortion and two-tone suppression was dependent on the presence of a cochlear nonlinearity. PMID- 8473245 TI - Frequency-related differences in the speed of human auditory processing. AB - Three experiments were performed, two comparing the peak latencies of auditory evoked potentials (AEPs) elicited by 250 Hz and 4000 Hz tone pips and a third comparing simple reaction times (RTs) to the same stimuli. In the AEP experiments, the latencies of brainstem, middle and long-latency components were delayed following 250 Hz tone pips in comparison with the latencies of the same components evoked by loudness-matched 4000 Hz tones. Frequency-related latency differences increased with component latency, ranging from less than 1.0 ms for wave V of the brainstem AEP, to more than 20.0 ms for the cortical N1 component. Interpeak latency differences were also significantly lengthened following the 250 Hz tone pips. In the behavioral study, RTs were 14.6 ms slower following 250 than 4000 Hz tone pips. The results suggest that the time required for the sensory analysis of auditory signals varies inversely with their frequency. PMID- 8473246 TI - The influence of temporal pattern of stimulation on delay tuning of neurons in the auditory cortex of the FM bat, Myotis lucifugus. AB - In echolocating bats, delay-sensitive neurons show facilitative responses to simulated pulse-echo pairs at particular echo delays. Three experiments examined how the temporal pattern of stimulation affected the delay tuning of neurons in the auditory cortex of the awake FM bat, Myotis lucifugus. First, delay tuning was compared using a series of pulse-echo pairs fixed in echo delay ('standard' stimuli), and a series of pulse-echo pairs in which successive sound pairs decreased by a fixed echo-delay step ('approach' stimuli). Similar best delays were measured with both stimulation patterns presented at repetition rates in which the neuron was delay-sensitive. At the higher delay-sensitive pulse repetition rates, approach stimuli evoked larger delay-dependent responses. Second, approach stimuli were fixed at different intertrial intervals. The best delay was unaffected by intertrial interval, although some neurons showed larger responses for longer intertrial intervals (0.5, 1.0 s), especially at the higher delay-sensitive pulse repetition rates. Third, approach stimuli were fixed at different echo-delay steps to simulate target velocity. The majority of neurons showed some sensitivity to echo-delay step, with clear preference for target velocity mainly between 1.8-7.0 m/s. This suggests that delay-sensitive neurons compute target velocity by rate of change of echo delay over successive echoes. Thus, response properties of cortical neurons are influenced by dynamic acoustic conditions found in target-directed flight. PMID- 8473247 TI - Increment detection of bandlimited noises in the chinchilla. AB - A positive reinforcement, adaptive tracking procedure was used to study the intensity discrimination abilities of six chinchillas to noise signals. Increment detection thresholds were obtained using a two-down, one-up tracking rule. The effect of overall noise masker level and the effect of noise bandwidth on increment detection thresholds were studied. The continuous noise masker and the signal increment had equal bandwidths. Increment detection thresholds are independent of overall level for wideband noise; the asymptotic DL for wideband noise is 1.334 dB. In addition, increment detection thresholds decrease as the bandwidth of the noise increases. The observed slope of the bandwidth function for the chinchilla is independent of overall level and is around -2.8 dB/decade. The slope of the bandwidth function obtained for the chinchilla is similar to values reported for human subjects under similar conditions, but is less than the slope predicted by the ideal energy detector model. PMID- 8473248 TI - The innervation of the organ of Corti in the rat. AB - To date our knowledge of the baso-apical distribution of the afferent and efferent nerve fibers innervating the organ of Corti is only fragmentary. This study makes an effort to lay the basis for a comprehensive analysis of cochlear innervation. Using a quantitative electronmicroscopic method, the fiber density of all cochlear fibers along the entire length of the cochlear duct was investigated in adult rats, Rattus norvegicus. Myelinated and unmyelinated nerve fibers in the primary osseous spiral lamina and afferent and efferent nerve fibers to the outer hair cells (OHCs) in the tunnel of Corti were counted. The rat cochlea is innervated by 19000 nerve fibers which consist of 79% afferent and 21% efferent fibers. The inner hair cells (IHCs) are innervated by 14000 afferent and 2000 efferent fibers. The OHCs are innervated by 1000 afferent and 2000 efferent fibers. The maximum fiber density of IHC afferents, OHC afferents and IHC efferents was found in the middle of the cochlea. This corresponds to the region at the basilar membrane where the frequency range of maximum sensitivity is located [8 kHz-31 kHz; Kelly and Masterton, J. Comp. Physiol. Psychol. 91, 930 936 (1977)]. The efferent nerve fibers to the OHCs consists of two different morphological sub-types: large fibers containing mitochondria and neurotubules (type I) and small fibers containing neurofilaments (type II). The fiber density of type I OHC efferents decreases from base to apex corresponding to the frequency dispersion along the basilar membrane. The fiber density of type II OHC efferents has maxima at the base and at the apex and a minimum in the middle of the cochlea. This minimum corresponds to the region at the basilar membrane where the frequency range of maximum sensitivity is located. PMID- 8473249 TI - Binaural interaction in auditory evoked potentials: brainstem, middle- and long latency components. AB - Binaural interaction occurs in the auditory evoked potentials when the sum of the monaural auditory evoked potentials are not equivalent to the binaural evoked auditory potentials. Binaural interaction of the early- (0-10 ms), middle- (10-50 ms) and long-latency (50-200 ms) auditory evoked potentials was studied in 17 normal young adults. For the early components, binaural interaction was maximal at 7.35 ms accounting for a reduction of 21% of the amplitude of the binaural evoked potentials. For the middle latency auditory evoked potentials, binaural interaction was maximal at 39.6 ms accounting for a reduction of 48% of the binaural evoked potential. For the long-latency auditory evoked potentials, binaural interaction was maximal at 145 ms accounting for a reduction of 38% of the binaural evoked potential. In all of the auditory evoked potentials binaural interaction was long lasting around the maxima. The binaural interaction component extends for several milliseconds in the brainstem to tens of milliseconds in the middle- and long-latency components. Binaural interaction takes the form of a reduction of amplitude of the binaural evoked potential relative to the sum of the monaural responses, suggests that inhibitory processes are represented in binaural interaction using evoked potentials. Binaural processing in the auditory pathway is maximal in the time domain of the middle latency components reflecting activity in the thalamo-cortical portions of the auditory pathways. PMID- 8473250 TI - Effects of active student response during error correction on the acquisition, maintenance, and generalization of sight words by students with developmental disabilities. AB - We used an alternating treatments design to compare the effects of active student response error correction and no-response error correction during sight word instruction. Six students with developmental disabilities were provided one-to one daily sight word instruction on eight sets of 20 unknown words. Each set of 20 words was divided randomly into two equal groups. Student errors during instruction on one group of words were immediately followed by the teacher modeling the word and the student repeating it (active student response instruction). Errors on the other group of words were immediately followed by the teacher modeling the word while the student attended to the word card (no response instruction). For all 6 students, the active student response error correction procedure resulted in more words read correctly during instruction, same-day tests, next-day tests, 2-week maintenance tests, and generality tests (words read in sentences). PMID- 8473251 TI - Teaching children with autism to initiate to peers: effects of a script-fading procedure. AB - A script that was systematically faded from end to beginning was used to teach peer initiations about recently completed, current, and future activities. The effectiveness of the script-fading procedure was assessed via a multiple baseline design across 4 children with autism. During baseline, the children seldom initiated to peers, although all had previously acquired some functional expressive language and sometimes spontaneously addressed adults. When the script was introduced, peer initiations increased, and as the script was faded, unscripted initiations increased. With the minimal written prompts available in the final fading steps, initiations generalized to a different setting, time, teacher, and activity; and for 3 of the 4 children, peer initiations were maintained at a 2-month follow-up. After the script was faded, the participants' levels of peer initiations were within the same range as a normative sample of 3 nondisabled youngsters. The script-fading procedure enabled children with severe social and verbal deficits to practice context-specific, peer-directed generative language that was not prompted by adults or peer confederates. PMID- 8473252 TI - Effects of signaling invasive procedures on a hospitalized infant's affective behaviors. AB - We report the effects of using a visual and auditory stimulus signaling impending painful medical procedures versus "safe" periods on the affective behavior of a hospitalized infant. The results of a reversal design suggested that the signaling procedures increased positive behaviors and decreased negative behaviors during both noninvasive and invasive caregiver events. PMID- 8473253 TI - Momentum versus extinction effects in the treatment of self-injurious escape behavior. AB - An individual's self-injurious escape behavior was treated using a high probability instructional sequence with and without extinction. When presented alone, the high-probability sequence did not reduce self-injurious behavior. When escape extinction was implemented either alone or in combination with the high probability sequence, self-injury decreased and compliance increased, suggesting that extinction may be a necessary component of the treatment for behavior problems maintained by escape. PMID- 8473254 TI - Programming participation in family activities for children with autism: parents' use of photographic activity schedules. AB - The parents of 3 boys with autism were taught to help their children follow photographic activity schedules depicting a variety of home-living tasks. A multiple baseline across participants showed that the home-based intervention produced increases in children's engagement and social initiations and decreases in disruptive behavior, which were maintained for as long as 10 months. PMID- 8473255 TI - Reduction of self-injurious hand mouthing using response blocking. AB - We evaluated a response-blocking procedure for reducing the self-injurious hand mouthing of 2 adults with profound disabilities. The procedure reduced mouthing in both cases. The results suggest research is warranted to delineate the behavioral process responsible for the effect of response blocking and to determine the procedure's long-term utility. PMID- 8473256 TI - Functional communication training with and without extinction and punishment. AB - Functional communication training has been reported to be a promising treatment for severe behavior problems. In this study, functional communication training alone and combined with extinction and/or punishment was evaluated for 4 clients with severe retardation, behavior problems, and communication deficits. The participants were inpatients on a hospital unit for treatment of severe behavior disorders. They received individualized interventions based on functional assessment that included reinforcement of a communication response with the same function as their destructive behavior. Results showed that for some patients, functional communication training was not sufficient to produce clinically significant reductions in destructive behavior, and the combination of training plus punishment produced the largest and most consistent reductions. PMID- 8473257 TI - Impulsivity in students with serious emotional disturbance: the interactive effects of reinforcer rate, delay, and quality. AB - We conducted two studies extending basic matching research on self-control and impulsivity to the investigation of choices of students diagnosed as seriously emotionally disturbed. In Study 1 we examined the interaction between unequal rates of reinforcement and equal versus unequal delays to reinforcer access on performance of concurrently available sets of math problems. The results of a reversal design showed that when delays to reinforcer access were the same for both response alternatives, the time allocated to each was approximately proportional to obtained reinforcement. When the delays to reinforcer access differed between the response alternatives, there was a bias toward the response alternative and schedule with the lower delays, suggesting impulsivity (i.e., immediate reinforcer access overrode the effects of rate of reinforcement). In Study 2 we examined the interactive effects of reinforcer rate, quality, and delay. Conditions involving delayed access to the high-quality reinforcers on the rich schedule (with immediate access to low-quality reinforcers earned on the lean schedule) were alternated with immediate access to low-quality reinforcers on the rich schedule (with delayed access to high-quality reinforcers on the lean schedule) using a reversal design. With 1 student, reinforcer quality overrode the effects of both reinforcer rate and delay to reinforcer access. The other student tended to respond exclusively to the alternative associated with immediate access to reinforcers. The studies demonstrate a methodology based on matching theory for determining influential dimensions of reinforcers governing individuals' choices. PMID- 8473258 TI - Analysis of a simplified treatment for stuttering in children. AB - We investigated the effectiveness of a simplified program for the treatment of stuttering in children. The simplified treatment included awareness training, in which the subjects learned to detect every occurrence of stuttering; training a response incompatible with stuttering, which involved relaxation and regulation of air flow over the larynx when speaking; and social support, which involved parent-delivered prompts and praise of children's use of the techniques in everyday environments. Eight children were treated in their homes with the simplified treatment, in a multiple baseline across subjects design, and all reached the criterion level of less than 3% words stuttered. In addition, the reduction in stuttering generalized to the school setting and was maintained at posttreatment (10 to 13 months). The subjects' rates of speech remained stable throughout baseline and treatment. Pretreatment and posttreatment ratings by the parents showed that they found treatment to be both acceptable and credible. Finally, social validity measures revealed a noticeable improvement in the subjects' speech to parents and speech pathologists. PMID- 8473259 TI - Teaching choice making during social interactions to students with profound multiple disabilities. AB - We taught 4 students with profound multiple disabilities to use a microswitch communication system to request a change in recreational stimuli during social interactions with nondisabled peers. In Study 1, we conducted a preference assessment across a range of stimuli for each student. The most and least preferred stimuli were incorporated into microswitch communication system training in Study 2. During the second study, 3 of the 4 students (a) learned to use the microswitch communication system to control stimulus presentation, (b) more clearly differentiated their time among stimuli, and (c) increased their level of general alertness. Study 3 extended the use of the microswitch communication system to social interactions with nondisabled peers. Two students were more engaged in interactions when they chose when to change stimuli; 1 student was more alert when a peer chose when to change activities; a 4th student showed an undifferentiated pattern. The outcomes of the investigation are discussed in terms of the effects of controlling stimulus presentation on the behavior of students with profound multiple disabilities and the stability of preference hierarchies over time. PMID- 8473260 TI - Effects of memory aids on the dyadic conversations of individuals with dementia. AB - The effects of a prosthetic memory aid on the conversational content and social skills of dyads with dementia were evaluated. Six individuals with moderate to severe dementia served as either subject or partner in dyads during 5-min conversational probes conducted three times per week in day-care and nursing-home settings. During phases when a memory aid, consisting of personally relevant picture and sentence stimuli, was available, most subjects used their own aid to improve the quality of conversations by increasing the frequency of on-topic statements, diminishing nonproductive utterances, lengthening their conversational turn, and/or increasing the frequency of turns taken. Most partners demonstrated awareness of social discourse conventions by appropriately relinquishing conversational dominance, decreasing both content and nonproductive utterances, and increasing acknowledging or affirmative comments when subjects used memory aids. Naive judges' ratings of aided and unaided conversational samples on seven conversational dimensions reflected differences in perceptions of significant improvement as a function of the conversational discourse style of each dyad. PMID- 8473261 TI - Teaching children with autism to use photographic activity schedules: maintenance and generalization of complex response chains. AB - We used a graduated guidance procedure to teach 4 boys with autism to follow photographic activity schedules to increase on-task and on-schedule behavior. The multiple baseline across participants design included baseline, teaching, maintenance, resequencing of photographs, and generalization to novel photographs phases. The results indicated that photographic activity schedules (albums depicting after-school activities) produced sustained engagement, and skills generalized to a new sequence of photographs and to new photographs. The acquisition of schedule-following skills enabled these children with severe developmental disabilities to display lengthy response chains, independently change activities, and change activities in different group home settings in the absence of immediate supervision and prompts from others. PMID- 8473262 TI - The role of attention in the treatment of attention-maintained self-injurious behavior: noncontingent reinforcement and differential reinforcement of other behavior. AB - Because there are potentially serious limitations to differential reinforcement of other behavior (DRO) (which is probably the most widely used treatment procedure for behavior problems), we examined an alternative procedure- noncontingent reinforcement (NCR). Three females with developmental disabilities, all of whom engaged in severe self-injurious behavior, participated. During a pretreatment functional analysis, each subject's self-injury was shown to be differentially sensitive to social attention as a maintaining consequence. Next, each subject was exposed to a DRO treatment and an NCR treatment. During DRO, attention was delivered contingent on the absence of self-injury for prespecified intervals. During NCR, attention was delivered on a fixed-time schedule that was not influenced by the subject's behavior. Results showed that both procedures were highly effective in reducing self-injury, probably because the functional reinforcer for self-injury was used during treatment. Furthermore, there was evidence that NCR attenuated several of the limitations of DRO. These results are particularly interesting in light of the long experimental history of NCR as a control rather than as a therapeutic procedure. PMID- 8473263 TI - Relative effects of whole-word and phonetic-prompt error correction on the acquisition and maintenance of sight words by students with developmental disabilities. AB - We used an alternating treatments design to compare the effects of two procedures for correcting student errors during sight word drills. Each of the 5 participating students with developmental disabilities was provided daily one-to one instruction on individualized sets of 14 unknown words. Each week's new set of unknown words was divided randomly into two groups of equal size. Student errors during instruction were immediately followed by whole-word error correction (the teacher stated the complete word and the student repeated it) for one group of words and by phonetic-prompt error correction (the teacher provided phonetic prompts) for the other group of words. During instruction, all 5 students read correctly a higher percentage of whole-word corrected words than phonetic-prompt corrected words. Data from same-day tests (immediately following instruction) and next-day tests showed the students learned more words taught with whole-word error correction than they learned with phonetic-prompt error correction. PMID- 8473264 TI - "Normal" breast cells adjacent to a tumor grown in long-term three-dimensional culture. PMID- 8473265 TI - TGF-beta gene expression depends on tissue architecture. PMID- 8473266 TI - New model of vascular cell repair in vitro. PMID- 8473267 TI - A novel human glioma cell line from pituitaries. PMID- 8473268 TI - Insulin-like growth factor-II receptor expression in normal and N-methyl-N'-nitro nitrosoguanidine exposed cell lines: assessment by flow cytometry. PMID- 8473269 TI - Factors regulating the emergence of spontaneous and X-ray-induced variants in primary rat tracheal epithelial cell cultures. AB - A series of experiments have been carried out to identify those factors that affect the number of altered populations detected in control, nonexposed, and radiation-exposed primary cultures of rat tracheal epithelial cells. The number of colony forming cells per milliliter of culture medium and the frequency with which the culture medium is changed seemed to be the most critical factors regulating the emergence of induced and spontaneous variants. Increasing the number of cells plated so that of colony forming cells increase from 25 to 200 per ml, regardless of the dish size used, was associated with a 200-fold decline in the frequency of spontaneous variants and a 40-fold decline in X-ray-induced variants. Increasing the interval between medium changes from 3 to 7 days after the first week of culture was associated with a 10-fold decrease in the frequency of spontaneous variants. The frequency of spontaneous and induced variants is markedly less dependent on culture density at densities between 150 and 600 colony forming cells per ml. The type of medium used to establish primary cultures had little effect on the frequency of variants detected. Similarly, when assays were performed at densities in excess of 150 colony forming cells per ml the frequency of spontaneous and x-ray-induced variants was not affected by the absence of epidermal growth factor, increased levels of calcium (final concentration, 0.8 mM), or by removal of pyruvate from the selection medium. PMID- 8473270 TI - Isolation and culture of rat superior mesenteric artery smooth muscle cells. AB - The structure and function of vascular smooth muscle cells have been extensively investigated with the aid of in vitro culture techniques. The majority of studies have utilized aortic tissue as the source of cells. We present here a method for isolating and culturing smooth muscle cells of the rat superior mesenteric artery, an elasto-muscular vessel that is structurally and functionally different from the aorta. Cells were isolated from partially digested explants and characterized by immunochemical and biochemical techniques. Unlike cultured fibroblasts, the cultured cells stained positive for smooth muscle specific actin. The cells also produced laminin and type IV collagen in culture. This method provides a means for the isolation of large numbers of viable smooth muscle cells from the superior mesenteric artery which can be propagated in culture for in vitro study. PMID- 8473271 TI - Retinoic acid modulation of alpha(1-->2) fucosyltransferase activity and sensitivity of tumor cells to LAK-mediated cytotoxicity. AB - We examined the effects of all-trans retinoic acid (RA) on alpha(1-->2) fucosyltransferase activity and sensitivity to LAK-mediated cytotoxicity in two rat colon carcinoma cell lines differing by their glycosylation state and their tumorigenic potential. RA induced a decrease in alpha(1-->2) fucosyltransferase activity in the more tumorigenic variant PROb. Fucosyltransferase mRNA levels were not affected by RA treatment in PROb cells, suggesting a posttranscriptional control. This inhibition was accompanied by a decreased expression of fucosylated membrane glycoconjugates and by a significant increase in the sensitivity to LAK mediated cytotoxicity. REGb cells, which exhibited a very low enzymatic activity and very few fucosylated glycoconjugates, were more sensitive to LAK-lysis than PROb cells and were not affected by RA treatment. PMID- 8473272 TI - Differences in growth of neurons from normal and regenerated teleost spinal cord in vitro. AB - Explants and dissociated cells from normal adult spinal cord and regenerating cord of the teleost Apteronotus albifrons were grown in vitro for periods of 8 to 12 wk. During this time the neurons showed extensive neurite outgrowth. Neurite outgrowth from tissue explants and dissociated cells of regenerated spinal cord starts sooner and is more profuse than that from normal (unregenerated) cord. Neurite outgrowth is maximized by using adhesive substrata and a high density of explants or dissociated cells. Inasmuch as Apteronotus does regenerate its spinal cord naturally after injury, whereas mammals do not, this culture system will be useful to study factors that control (permit) regeneration of spinal neurons in this adult vertebrate. PMID- 8473273 TI - Polarized secretion of tissue-plasminogen activator in cultured thyroid cells. AB - We studied the polarized secretion of tissue-type plasminogen activator in porcine thyroid cells cultured as a monolayer on porous bottom chambers. The presence of tissue-type plasminogen activator was detected by zymographic analysis on two independent media that were in contact either with the apical surface or with the basolateral membrane. The amount of tissue-type plasminogen activator was determined in both media by ELISA and enzyme assay. Measurable tissue-type plasminogen activator activity was found in the basal but not in the apical medium. However, on zymogram, a lytic zone corresponding to tissue-type plasminogen activator was visible in both media. In addition, a lytic band at 130 kDa suggested presence of a complex formed by tissue-type plasminogen activator and an inhibitor. Preferential basolateral tissue-type plasminogen activator antigen secretion (70%) has been observed, showing the possible relation between tissue-type plasminogen activator and extracellular matrix components. Neither tissue-type plasminogen activator level nor polarized secretion seemed to be regulated by thyrotropin (0.1 mU/ml). PMID- 8473274 TI - Serum-free medium for long-term growth, freezing, cloning and fusion of myelomas and hybridomas. PMID- 8473275 TI - Endothelial proliferation and adhesivity. PMID- 8473276 TI - The role of family education. AB - A mentally ill relative not only represents a tragedy for a family but also poses a challenge to the practitioner trying to understand the family's perspective as they attempt to cope with this profoundly difficult situation. Such an understanding calls for a new professional paradigm that includes the family in the treatment process, taking into account the subjective experiences and objective burdens of mental illness. When families are well-informed about mental illness, they can become allies in treatment, control stress, and participate in problem-solving. PMID- 8473277 TI - Mental health care policy in the 1990s: discrimination in health care coverage of the seriously mentally ill. AB - The severely mentally ill face many roadblocks, not the least of which is discrimination by the government and by insurance companies. The inadequate coverage allowed the severely mentally ill by the insurance industry, Medicare, and Medicaid is often as little as one fifth or less the coverage allowed other serious illnesses. This inequity not only contributes to the terrible stigma of mental illness, but also greatly increases patient suffering and results in needless fatalities--suicides that could have been prevented by properly reimbursed treatment. As the federal government prepares for essential health care cost reform, it is imperative that policy leaders, physicians, and mental health care advocates demand equal treatment under the law for the severely mentally ill. The Equitable Health Care for Severe Mental Illnesses Act of 1992 can provide a model for such action. PMID- 8473278 TI - A system approach to reducing relapse in schizophrenia. AB - Successful treatment of schizophrenia depends on understanding the nature of the disorder and providing a system of care with the primary locus in the community. Care must be continuous and must fulfill a wide variety of needs required for patients to make a stable adjustment to the community. The Dane County, Wisconsin, integrated system of community-based care is a proven model. It is based on the above principles and has resulted in more patients living independently and working productively, with fewer hospitalizations. The majority of funding for the Dane County Mental Health System is allocated to community services making it possible to offer a comprehensive set of programs. These programs work cooperatively to do whatever is needed to help patients achieve a stable life, of decent quality, in the community. The conceptual framework for the treatment of persons with schizophrenia, the principles of treatment, and a system of care based on those principles is discussed. PMID- 8473279 TI - The anaerobic ribonucleotide reductase from Escherichia coli. PMID- 8473280 TI - Phosphorylation and dephosphorylation catalyzed in vitro by purified components of the nitrate sensing system, NarX and NarL. AB - The regulation of specific gene expression by nitrate in Escherichia coli is mediated by the NarX/NarQ-NarL system. Based on sequence homologies with a family of two-component regulatory systems in bacteria, NarL has been identified as a putative response regulator while NarX and NarQ were proposed to be alternative membrane-associated sensors that activate NarL in the presence of nitrate. To investigate the interaction of NarX and NarL in vitro, both proteins were purified from overproducing strains. Purified NarX was rapidly labeled when incubated with [gamma-32P] ATP but not with [alpha-32P]ATP in a reaction that required Mg2+ but was unaffected by nitrate. Incubation of the labeled NarX with purified NarL resulted in the transient phosphorylation of NarL. Both the phosphorylation and dephosphorylation of NarL required Mg2+, and neither reaction was affected by the presence of nitrate. NarL-phosphate, stabilized by the addition of EDTA, ran as a monomer on gel filtration. Dephosphorylation of the isolated NarL-phosphate required the addition of both Mg2+ and the NarX protein. The relative stabilities of the phosphorylated forms of the two proteins at different pH values were consistent with the proposal that, in analogy to other related two-component regulatory systems, NarX and NarL were phosphorylated on specific histidine and aspartate residues, respectively. PMID- 8473281 TI - Specificity of Goodpasture autoantibodies for the recombinant noncollagenous domains of human type IV collagen. AB - Type IV collagen has recently emerged as a family composed of five known chains (alpha 1-alpha 5), each of which contains a carboxyl-terminal noncollagenous domain (NC1) of approximately 230 amino acids. The NC1 domain of the alpha 3(IV) chain is the probable target for autoantibodies in patients with Goodpasture syndrome (GP), as evidenced from studies employing bovine type IV collagen. In the present experiments, the specificity of GP antibodies for the five NC1 domains of human type IV collagen was determined by using recombinant NC1 domains as the antigen. cDNAs encoding each NC1 domain were expressed in E. coli as fusion proteins with a 6-histidine amino-terminal leader. The recombinant NC1 monomers r alpha 1(IV), r alpha 2(IV), r alpha 3(IV), r alpha 4(IV), and r alpha 5(IV) were purified by affinity chromatography to the fusion protein using a nickel resin column, and then characterized by electrophoresis and immunoblot analysis using chain-specific peptide antibodies. The specificity of GP antibodies from four patients to these recombinant proteins was then further evaluated by immunoblot analysis and enzyme-linked immunosorbent assay measurements. The GP antibodies reacted strongly with the r alpha 3(IV) NC1 domain but were not reactive when tested against the other four recombinant monomers. In contrast, neither antisera from patients with two other forms of autoimmune disease (anti-tubular basement membrane disease and Wegener's syndrome) nor normal control sera bound to any of the recombinant NC1 moieties. These results unambiguously establish that GP antibodies are specifically targeted to the NC1 domain of the alpha 3(IV) chain of human type IV collagen. The findings also establish a methodology for large scale preparation of r alpha 3(IV) NC1 domain for use in diagnostic tests and development of therapeutic procedures and offer a strategy for the elucidation of a more complete GP epitope by site-directed mutagenesis. PMID- 8473282 TI - Calcium-dependent cyclosporin A-sensitive activation of the interleukin-2 promoter by p56lck. AB - T-cell antigen receptor engagement results in suboptimal activation of protein kinase C and a prolonged increase in intracellular free calcium concentration. These signals, in combination with stimulation via accessory molecules usually supplied by the antigen presenting cell, activate expression of interleukin-2 (IL 2) and initiate autocrine growth. The lymphocyte-specific tyrosine kinase p56lck is physically associated with CD4 and is brought into close proximity of the intracellular domain of the antigen receptor by CD4 recognition of the major histocompatibility complex during antigen presentation. p56lck activation enhances and may be essential for antigen receptor signaling. We report that a constitutively active form of p56lck delivers a signal which contributes to IL-2 promoter activation. The signal substituted for a calcium-mobilizing signal in a Jurkat cell model of T-cell activation. The activation was sensitive to EGTA and cyclosporin A, indicating that p56lck functions at an early stage of the calcium mediated pathway. The transcription factor NF-AT mediated, at least in part, the p56lck activation of IL-2 expression. In addition, activated p56lck synergized with constitutively active p21Ha-ras, which can replace protein kinase C activation, resulting in activation of NF-AT in the absence of external signals. PMID- 8473283 TI - A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. AB - A cDNA has been cloned from rabbit brain that is a new member of the emerging family of Na(+)-dependent plasma membrane transporters for several neurotransmitters and structurally related compounds. Functional expression of this cDNA in COS-7 cells identifies its product as a Na(+)- and Cl(-)-dependent creatine transporter with a Km of approximately 35 microM. Its creatine transporter activity is efficiently antagonized by 3-guanidinopropionate, a well characterized alternative substrate of creatine transport in several tissues, and by 4-guanidinobutyrate. More distant structural analogues of creatine are much less efficient or inactive as antagonists, indicating a high substrate specificity of the transporter. Northern blot hybridization detects the expression of its mRNA in most tissues tested, most prominently in kidney, heart, and muscle, but not in liver and intestine. A full-length cDNA clone was also isolated from a muscle cDNA library and found to contain the same coding sequence. Substrate affinity and specificity of the cloned transporter are very similar to the endogenous creatine transporter of the COS-7 cells and to the creatine transport activities of several cell types described in the literature. Moreover, its mRNA is most abundant in the tissues known to possess high creatine uptake capacity. PMID- 8473284 TI - Evolution of the type II hexokinase gene by duplication and fusion of the glucokinase gene with conservation of its organization. AB - The type I, II, and III isozymes of mammalian hexokinase (100 kDa) all consist of a duplicated, highly homologous peptide sequence, each half of which is very similar to that of glucokinase (type IV hexokinase, 50 kDa) and yeast hexokinase (50 kDa). We isolated a genomic clone of type II hexokinase that contained five exons encoding the C-terminal region of type II hexokinase. The positions of intron insertions of the isolated clone were found to be identical with those of the glucokinase gene, indicating that the type II hexokinase gene arose from the glucokinase gene. Furthermore, we prepared two DNA fragments of the type II hexokinase gene amplified from total genomic DNA. The exons in these fragments were found to be constructed by linkage of the coding region of the last exon and second exon of the glucokinase gene, indicating that the hexokinase gene arose by fusion of two glucokinase genes. These results clearly show that the mammalian hexokinase gene evolved from the glucokinase gene by gene duplication and fusion with conservation of the gene organization. PMID- 8473285 TI - Sinusoidal oscillations in intracellular calcium requiring negative feedback by protein kinase C. AB - Stimulation of mouse lacrimal acinar cells with submaximal concentrations of the muscarinic agonist, methacholine, resulted in an increase in intracellular calcium ([Ca2+]i), which took the form of sinusoidal oscillations. These oscillations were relatively constant (approximately 4-5/min) regardless of the methacholine concentration, suggesting that the oscillations arise from an oscillating negative feedback in the signal transduction pathway. This negative feedback appears to involve oscillations in protein kinase C activity because the oscillations were prevented by activation, inhibition, or down-regulation of protein C. Activation of protein kinase C with phorbol esters inhibited the methacholine-induced [Ca2+]i signal and formation of the Ca2+ mobilizing messenger, inositol 1,4,5-trisphosphate. [Ca2+]i signals elicited by intracellular introduction of inositol phosphates did not oscillate and were not affected by activators or inhibitors of protein kinase C. Thus, the constant frequency [Ca2+]i oscillations appear to result from a negative feedback loop involving inhibition of inositol trisphosphate production by protein kinase C. PMID- 8473286 TI - His865 is the catalytically important histidyl residue of Syrian hamster 3 hydroxy-3-methylglutaryl-coenzyme A reductase. AB - Involvement in catalysis of a histidyl residue of Syrian hamster 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase was suggested by the ability of diethyl pyrocarbonate to abolish catalytic activity, accompanying spectral changes, and reactivation by hydroxylamine. The 7 histidines present in the catalytic domain of the hamster enzyme were changed to glutamine (His474, His487, His634, His751, His860, and His865), lysine (His865), or tyrosine (His868). Overexpression in Escherichia coli yielded six soluble mutant proteins, one insoluble protein (H634Q), and one which was degraded in vivo (H487Q). Following purification to homogeneity, mutant enzymes H474Q, H751Q, H860Q, and H868Y had essentially wild-type catalytic activity, while mutant enzymes H865K and H865Q had less than 0.6% wild-type activity. The low activity of mutant enzymes H865K and H865Q is unlikely to reflect altered structural integrity since both chromatographed on affinity supports like wild-type enzyme and had Km values for (S)-HMG-CoA (31 and 16 microM) and for NADPH (60 and 24 microM) close to those for wild-type enzyme (31 and 52 microM for (S)-HMG-CoA and NADPH, respectively). His865 of hamster HMG-CoA reductase, the histidine of the consensus Leu-Val-Xaa Ser-His-Met-Xaa-Xaa-Asn-Arg-Ser motif and the only histidine conserved among the catalytic domains of all HMG-CoA reductases, thus appears to be a general acid/base functional in catalysis. PMID- 8473287 TI - Domain structure and domain-domain interactions in human coagulation factor IX. AB - Coagulation factor IX has the modular composition Gla-(EGF)2-SP, where Gla, EGF, and SP represent the gamma-carboxy-Glu-rich, epidermal growth factor-like, and serine protease modules, respectively. The protein melts in two distinct temperature regions. The SP module melts at lower temperature between 42 and 55 degrees C, depending on the pH, with irreversible loss of esterolytic activity. The endotherm corresponding to this transition is readily described by a two state transition indicating the melting of a single cooperative unit. A thrombin generated 12-kDa fragment representing the COOH-terminal half of the SP module and a 45-kDa fragment containing the NH2-terminal half of the SP module and the rest of the molecule can be separated by exclusion chromatography in 3 M urea and recombined in its absence. Both fragments retain a compact structure as evidenced by melting transitions near 60 degrees C at neutral pH. This indicates that the SP module contains two independently folded domains that strongly interact with each other and seem to merge into one cooperative unit in the intact protein. At low pH at high temperature a second peak appears which is also observed in a 19 kDa fragment containing the EGF modules. Thermodynamic analysis of this second peak showed that the two EGF modules are independently folded and provided evidence for a weak interaction between them. Fluorescence and CD measurements indicated that the secondary structure of the isolated 6-kDa Gla fragment is substantially increased in the presence of Ca2+. The Ca2+-loaded Gla fragment undergoes a sigmoidal unfolding transition as revealed by fluorescence and CD measurements. This same transition in a 25-kDa Gla-(EGF)2 fragment was stabilized by more than 10 degrees C, indicating a strong interaction between the Ca(2+) loaded Gla and EGF domains. Thus, factor IX consists of five independently folded interacting domains. PMID- 8473288 TI - Binding of lipoprotein lipase to heparin. Identification of five critical residues in two distinct segments of the amino-terminal domain. AB - Binding to heparan sulfate governs many aspects of the physiological action and regulation of the lipolytic enzyme, lipoprotein lipase (LPL). In an attempt to identify the structural determinants which mediate this interaction, basic residues in three segments of the primary sequence of human LPL (residues 147 151, 279-282, and 292-304) were replaced with alanine, either singly or in various combinations, and variant proteins were subjected to affinity chromatography on heparin-Superose. Five basic residues in two distinct segments of the primary sequence were critical determinants of the high affinity for heparin manifested by the active enzyme (R279, K280, R282, K296, R297). By contrast, no such evidence could be detected for basic residues in the first cluster (K147, K148) or for other basic residues in the third cluster (K292, R294, K304), while the evidence for K300 was unresolved. The conformation of this heparin-binding domain can be inferred by reference to the three-dimensional structure of the homologous enzyme, pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. (1990) Nature 343, 771-774). Affinity of the active enzyme for heparin could not be reduced below a threshold, suggesting that other heparin binding determinants exist elsewhere in the molecule, as supported by recently published evidence (Davis, R. C., Wong, H., Nikazy, J., Wang, K., Han, Q., and Schotz, M. C. (1992) J. Biol. Chem. 267, 21499-21504). PMID- 8473289 TI - PACE/furin can process the vitamin K-dependent pro-factor IX precursor within the secretory pathway. AB - Factor IX is synthesized as a precursor polypeptide which requires proteolytic cleavage of the propeptide for functional activity. Expression of factor IX at high levels in Chinese hamster ovary (CHO) cells results in the secretion of a mixture of profactor IX and mature factor IX. We have studied whether the processing of profactor IX may be mediated by the recently discovered subtilisin like serine proteases PACE/furin and/or PACE4. Co-transfection of a PACE expression vector with a profactor IX expression vector resulted in the secretion of fully processed factor IX. In contrast, co-transfection of a PACE4 expression vector with a profactor IX expression vector did not increase processing of profactor IX to the mature form. A factor IX Arg-to-Thr mutation at the P1 position (residue 39) destroyed the ability for PACE to process profactor IX. Amino-terminal sequence analysis demonstrated that processing mediated by PACE occurred at the authentic site within profactor IX. The specificity of profactor IX processing by PACE was also evaluated by transfection of a vector encoding the serine protease inhibitor alpha 1-antitrypsin. Expression of wild-type alpha 1 antitrypsin, which does not inhibit PACE, did not influence processing of profactor IX mediated by co-expression of PACE. In contrast, the alpha 1 antitrypsin Pittsburgh mutant, which inhibits PACE, inhibited profactor IX processing activity mediated by transfected PACE as well as the endogenous CHO cell propeptide processing enzyme. Pulse-chase labeling indicated that PACE processed profactor IX late within the secretory pathway, although a secreted soluble mutant PACE was also capable of processing profactor IX in the conditioned medium. The results implicate PACE as a candidate for the enzyme that processes profactor IX in vivo. PMID- 8473290 TI - Ionizing radiation induces expression of interleukin 6 by human fibroblasts involving activation of nuclear factor-kappa B. AB - We here report that human lung fibroblasts respond to x-ray treatment (XRT) with release of interleukin (IL)-6. Synthesis of IL-6 upon ionizing radiation is preceded by an increase of IL-6 transcript levels resulting from transcriptional activation of the IL-6 gene. Analysis of deleted fragments of the IL-6 promoter indicated that transcriptional activation of the IL-6 promoter was due to enhanced binding activity of the transcription factor nuclear factor (NF)-kappa B. Although AP-1 did not participate in the rapid induction of the IL-6 promoter, its binding activity was also enhanced by XRT. In contrast to binding kinetics observed with NF-kappa B, AP-1 binding following XRT was biphasic with the second peak being dependent on de novo protein synthesis. In contrast, however, NF-IL-6 activity was not enhanced by XRT in fibroblasts. The introduction of both the NF kappa B- and the AP-1 recognition sequence conferred inducibility by XRT to a heterologous promoter, with reporter gene activity being maximal 24 or 48 h following XRT, respectively. Sequential activation of two distinct transcription factors might thus contribute to synchronize transcriptional activation of different genes participating in the x-ray response. PMID- 8473291 TI - Pituitary-specific repression of placental members of the human growth hormone gene family. A possible mechanism for locus regulation. AB - Five members of the human growth hormone (GH) gene family are located at a single locus on chromosome 17. Growth hormone is expressed in the pituitary under the control of the tissue-specific factor Pit 1/GHF-1, and chorionic somatomammotropin (CS) -A, -B, and -L, as well as placental GH variant, are expressed specifically in the placental syncytiotrophoblast. Despite this specificity in vivo, the CS-A promoter can bind Pit 1/GHF-1 and allow CS-A promoter activity in pituitary tumor cells after gene transfer. We have identified and characterized PSF sequences associated with only the placental members in the GH/CS locus which repress placental promoter activity > 90% in transfected pituitary cells. These sequences do not significantly affect promoter function in placental cells after gene transfer. Repressor activity correlates with binding of protein at two sites (PSF-A and PSF-B) with pituitary, but not placental, nuclear extracts. Competition studies suggest an interaction between PSF and Pit 1/GHF-1 proteins. These results indicate that PSF protein can repress CS-A promoter activity in a tissue-specific manner in vitro and provide a possible mechanism by which expression of placental members of the GH family are inhibited in the pituitary in vivo. PMID- 8473292 TI - Phosphatidic acid, lysophosphatidic acid, and lipid A are inhibitors of glycosylphosphatidylinositol-specific phospholipase D. Specific inhibition of a phospholipase by product analogues? AB - Previous work has suggested that the glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) purified from bovine serum is inhibited by phosphatidic acid (PA). In this study we report on the specificity and mechanism of this phenomenon using [3H]myristate-labeled variant surface glycoprotein dispersed in Nonidet P-40 as substrate. Inhibition of GPI-PLD by PAs (IC50 approximately 1 microM) was relatively independent of the length or degree of unsaturation of the fatty acyl chains. It was also observed that lysophosphatidic acid and several natural and synthetic lipid A preparations were inhibitory in the same concentration range. The inhibitory potency of PA, lysophosphatidic acid, and lipid A was dependent on the detergent concentration in the assay but in all cases this was in a large (i.e. > 100-fold) molar excess over the inhibitor. The inhibitory lipids did not affect substrate availability nor did they reduce hydrolysis of variant surface glycoprotein by a bacterial phosphatidylinositol specific phospholipase C. Studies with a wide range of other lipids, detergents, and phosphate esters indicated that inhibition was specific for lipids containing a phosphomonoester group. The data suggest that inhibition is due to a direct interaction between PA (or lipid A) and the GPI-PLD rather than an indirect effect on the substrate particle. PMID- 8473293 TI - Inhibition of apolipoprotein E degradation in a post-Golgi compartment by a cysteine protease inhibitor. AB - In our prior studies on lipoprotein stimulation of apolipoprotein E (apoE) secretion in HepG2 cells, it became clear that a proportion of the newly synthesized apoE was degraded intracellularly (Ye, S. Q., Olson, L. M., Reardon, C. A., and Getz, G. S. (1992) J. Biol. Chem. 267, 21961-21966). The present study was designed to determine the nature of the proteases and the intracellular sites involved in newly synthesized apoE degradation. The effect of seven protease inhibitors on total apoE levels was examined. Only N-acetyl-leucyl-leucyl norleucinal (ALLN), a cysteine protease inhibitor, significantly blocked apoE degradation in HepG2 cells. The amount of total apoE from cells chased with ALLN for 4 h was increased by 1.58 +/- 0.05-fold relative to the controls (n = 11, p < 0.01). ALLN extended the half-life of apoE from 2.61 h to 4.38 h (p < 0.01). This effect occurs in a post-Golgi compartment since in the presence of brefeldin A, ALLN had no effect on intracellular apoE levels. Chloroquine and NH4Cl significantly reduced apoE degradation; however, ALLN plus either of these reagents appear to have an additive effect. The amount of apoE in cells chased in Ca(2+)-free medium was significantly higher than that in cells chased in Ca(2+) containing medium (1.70 +/- 0.07-fold, n = 6, p < 0.01). ALLN plus Ca(2+)-free medium had no additive effect. ALLN had no significant influence on the degradation of albumin but had a similar effect on transfected apoE in Chinese hamster ovary cells. Overall, these data suggest that apoE may be degraded in a post-Golgi compartment of HepG2 and Chinese hamster ovary cells by lysosomal enzymes and cytosolic Ca(2+)-dependent cysteine proteases. ALLN inhibits the latter. PMID- 8473294 TI - Nucleotide binding properties of bovine brain uncoating ATPase. AB - Many functions of the 70-kDa heat-shock proteins (hsp70s) appear to be regulated by bound nucleotide. In this study we examined the nucleotide binding properties of purified bovine brain uncoating ATPase, one of the constitutively expressed members of the hsp70 family. We found that uncoating ATPase purified by ATP agarose column chromatography retained one ADP molecule bound per enzyme molecule which could not be removed by extensive dialysis. Since this bound ADP exchanged rapidly with free ADP or ATP, the inability to remove the bound nucleotide was not due to slow dissociation but rather to strong binding of the nucleotide to the uncoating ATPase. In confirmation of this view, equilibrium dialysis experiments suggested that the dissociation constants for both ADP and ATP were less than 0.1 microM. Schmid et al. (Schmid, S. L., Braell, W. A., and Rothman, J. E. (1985) J. Biol. Chem 260, 10057-10062) suggested that the uncoating ATPase had two sites for bound nucleotide, one specific for ATP and one binding both ATP and ATP analogues but not ADP. In contrast, we found that enzyme with bound ADP did not bind further adenosine 5'-(beta,gamma-imino)triphosphate or dATP, nor did more than one ATP molecule bind per enzyme even in 200 microM free ATP. These results strongly suggest that the enzyme has only one binding site for nucleotide. During steady-state ATP hydrolysis, 85% of the bound nucleotide at this site was determined to be ATP and 15% ADP; this is consistent with the rate of ADP release determined in the exchange experiments noted above, where ADP release was found to be six times faster than the overall rate of ATP hydrolysis. PMID- 8473295 TI - Kinetics of GLUT1 and GLUT4 glucose transporters expressed in Xenopus oocytes. AB - The predominant mechanism by which insulin activates glucose transport in muscle and adipose tissue is by affecting the redistribution of the facilitated hexose carriers, GLUT1 and GLUT4, from an intracellular site to the plasma membrane. A quantitative analysis of this process has been hampered by the lack of reliable determinations for kinetic constants catalyzed by each of these isoforms. In order to obtain such information, each transporter was expressed in Xenopus oocytes by the injection of mRNA encoding rat GLUT1 or GLUT4. Equilibrium exchange 3-O-methylglucose uptake was measured and the data fitted to a two compartment model, yielding Km = 26.2 mM and Vmax = 3.5 nmol/min/cell for GLUT1 and Km = 4.3 mM and Vmax = 0.7 nmol/min/cell for GLUT4. Measurement of the abundance of cell surface transporters was accomplished by two independent protocols: photolabeling with the impermeant hexose analog 2-N-4-(1-azi-2,2,2 trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2-propylamine and subcellular fractionation of oocytes. Data obtained by either technique revealed that the ratio of plasma membrane GLUT1 to GLUT4 was about 4; this paralleled the relative maximal velocities for hexose transport, indicating that the turn-over numbers for the two isoforms were the same. Moreover, measurement of the concentration of exofacially disposed transporters with 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl 1,3-bis(D-mannos-4 -yloxy)-2-propylamine allowed calculation of the turnover number to be about 20,000 min-1. These data indicate that, at low substrate concentrations, the catalytic efficiency of GLUT4 is significantly greater than GLUT1. Extrapolation to mammalian systems suggests that GLUT4 is responsible for virtually all of the hexose uptake in insulin-responsive targets, particularly in the presence of hormone. PMID- 8473296 TI - Characterization of transferrin-independent iron transport in K562 cells. Unique properties provide evidence for multiple pathways of iron uptake. AB - The present study characterizes the transport of nontransferrin (non-Tf) iron by K562 cells. Accumulation of radiolabel by cells incubated with 55Fe nitrilotriacetate (NTA) is a saturable process that is time and temperature dependent (Ea approximately 20 kcal/mol). Initial rate analysis of iron influx yields values of Vmax = 855 fmol/min/10(6) cells and apparent Km = 0.54 microM. NHCL4 and chloroquine, agents that block cellular acquisition of iron from Tf, do not interfere with assimilation from FeNTA, demonstrating that uptake is truly independent of the Tf-mediated pathway. Furthermore, the inactivation of this transport mechanism by limited proteolytic digestion on ice indicates that specific cell surface proteins are involved. The extent of radiolabel incorporation into heme and ferritin is the same regardless of whether K562 cells acquire iron from 55FeNTA via the cell surface mechanism or from 55Fe-Tf via receptor-mediated endocytosis. Unlike other Tf-independent iron transport pathways that have been described, the K562 cell transport mechanism is not inhibited by divalent cations such as Ni2+, Co2+, or Mn2+. Uptake from 55FeNTA can be blocked by Cu2+ but at concentrations > 1500-fold molar excess. However, Cd2+ is a fairly specific inhibitor of 55Fe uptake by K562 cells (IC50 approximately 50 microM). Additionally, the K562 cell transport mechanism is not Ca2+ dependent and does not appear to be regulated by extracellular iron salts, in contrast to features noted for non-Tf iron uptake by fibroblasts (Sturrock, A., Alexander, J., Lamb, J., Craven, C. M., and Kaplan, J. (1991) J. Biol. Chem. 265, 3139-3145; Kaplan, J., Jordan, I., and Sturrock, A. (1991) J. Biol. Chem. 266, 2997-3004). These unique characteristics of the K562 cell uptake mechanism suggest that multiple transport systems function in Tf-independent iron assimilation. PMID- 8473297 TI - Identification of potential active-site residues in the human poly(ADP-ribose) polymerase. AB - The carboxyl-terminal catalytic domain of the human poly(ADP-ribose) polymerase (PARP) exhibits sequence homology with the NAD(P)(+)-dependent leucine and glutamate dehydrogenases. To clarify the role played by some conserved residues between PARP and NAD(P)(+)-dependent dehydrogenases, point mutations were introduced into the whole enzyme context. Non-conservative mutations of Lys-893 (K893I) and Asp-993 (D993A) completely inactivate human PARP, whereas conservative and nonconservative mutations of Asp-914 (D914E and D914A, respectively) and Lys-953 (K953R and K953I, respectively) partially alter PARP activity. The consequences of conservative substitution of Lys-893 and Asp-993 on the kinetic properties of human poly(ADP-ribose) polymerase enzyme and the polymer it synthesizes suggest that these 2 amino acids are directly involved in the covalent attachment of the first ADP-ribosyl residue from NAD+ onto the acceptor amino acid. In addition, the recent resolution of the three-dimensional structure of the NAD(+)-linked glutamate dehydrogenase from Clostridium symbiosum (Baker, P.J., Britton, K.L., Engel, P.C., Farrants, G.W., Lilley, K.S., Rice, D.W., and Stillman, T.J. (1992) Proteins 12, 75-86) strongly supports our alignment with leucine and glutamate dehydrogenases and provides an interesting structural framework for the analysis of our results of site-directed mutagenesis. PMID- 8473298 TI - Inhibition by tentoxin of cooperativity among nucleotide binding sites on chloroplast coupling factor 1. AB - Tentoxin, a cyclic tetrapeptide produced by the fungus Alternaria tenuis, is a potent inhibitor of the chloroplast coupling factor 1 from certain sensitive species of plants. We have shown that the beta subunit is at least partly responsible for conferring sensitivity to the toxin. This was confirmed by Avni et al. (Avni, A., Anderson, J.D., Holland, N., Rochaix, J-D., Gromet-Elhanan, Z., and Edelman, M. (1992) Science 257, 1245-1247) who demonstrated the importance for tentoxin sensitivity of an acidic amino acid residue at position 83 in the beta subunit sequence. In this paper we show that the Ca(2+)-ATPase and Mg(2+) ATPase activities of CF1 lacking the delta and epsilon subunits, CF1(-delta epsilon), were fully sensitive to tentoxin, even after the gamma subunit is cleaved by trypsin into several smaller fragments. We also show that the isolated reconstitutively active beta subunit of CF1 does not effectively compete with CF1(-delta epsilon) for tentoxin binding. The results suggest that tight tentoxin binding requires the presence of at least the alpha and beta subunits but is independent of the delta and epsilon subunits. Tentoxin inhibited the release of a tightly bound molecule of ADP from CF1, which was induced by the binding of the ATP analogue adenylyl-beta,gamma-imidodiphosphate (AMP-PNP). AMP-PNP was shown previously (Shapiro, A.B., and McCarty, R.E. (1990) J. Biol. Chem. 265, 4340 4347) to cause two adenine nucleotide binding sites on CF1, sites 1 and 3, to switch their properties, possibly as part of an alternating site catalytic cooperativity mechanism (Boyer, P.D. (1989) FASEB J. 3, 2164-2178). It is proposed that the effect of tentoxin on catalytic cooperativity in CF1 results from tentoxin binding at an interface between alpha and beta subunits, preventing transfer of information between different nucleotide binding sites on the enzyme. PMID- 8473299 TI - Structure-function studies of yeast ferrochelatase. Identification and functional analysis of amino acid substitutions that increase Vmax and the KM for both substrates. AB - The molecular basis of the ferrochelatase defects was investigated in two "protoporphyric" and partially heme-deficient yeast mutants. Ferrochelatase, a mitochondrial inner membrane-bound enzyme, catalyzes the incorporation of ferrous iron into protoporphyrin, the last step in protoheme biosynthesis. The mutant cells made normal amounts of normal-sized ferrochelatase, as detected by immunoblotting. The mutations were identified by sequencing the mutant hem15 alleles amplified in vitro from mutant strains genomic DNA. A single nucleotide change, causing an amino acid substitution, was found in each mutant. Substitution of the conserved Ser-169 by Phe caused a 10-fold increase in Vmax and a 45- and 35-fold increase in the KM for protoporphyrin and metal, respectively. Replacement of Ser-174 by Pro produced the same effects, but to a lesser degree. There was a good correlation between the ferrochelatase defects measured in vitro and the heme synthesis deficiencies estimated in vivo. The decreased in vivo heme synthesis is probably due to the lower affinity of the mutant enzymes for iron. We propose that the region identified by the two close mutations contributes to the binding domains of metal and protoporphyrin. PMID- 8473300 TI - Distinct subdomains of human endothelin receptors determine their selectivity to endothelinA-selective antagonist and endothelinB-selective agonists. AB - The endothelin (ET) family of peptides acts via two subtypes of G-protein-coupled heptahelical receptors termed ETA and ETB, which have distinct rank orders of affinity to endothelin receptor agonists and antagonists. To delineate which portions of the receptor molecules determine ligand selectivity, we have constructed a series of chimeras between human ETA and ETB receptors and characterized the chimeric receptors expressed in heterologous cell lines by competitive radioligand binding analysis and by measuring agonist-induced transients of intracellular Ca2+. We demonstrate that the binding determinant for the ETB-selective agonists ET-3, BQ3020, and IRL1620 residues within the region spanning the putative transmembrane helices IV-VI and the adjacent loop regions. In contrast, the transmembrane helices I, II, III, and VII plus the intervening loop regions specify the selectivity for BQ123, an ETA-selective antagonist. BQ123 exhibited no detectable agonistic activity in all wild-type and chimeric receptors tested. A chimeric receptor that has the transmembrane helices IV-VI (and adjacent loops) from the ETB receptor inserted into the remaining regions from the ETA receptor binds both the ETA- and ETB-selective ligands with high affinities. Moreover, BQ123 competitively inhibits the binding of the amino terminally truncated ETB agonists, 125I-BQ3020 and 125I-IRL1620, to this chimeric receptor, suggesting that BQ123 is a mimic of the carboxyl-terminal linear portion of endothelins. These findings indicate that there are at least two separable ligand interaction subdomains within the endothelin receptors. PMID- 8473301 TI - Thapsigargin causes Ca2+ release and collapse of the membrane potential of Trypanosoma brucei mitochondria in situ and of isolated rat liver mitochondria. AB - Thapsigargin, previously reported to release Ca2+ from non-mitochondrial stores of different cell types, as well as nigericin, were found, when used at high concentrations, to release Ca2+ and collapse the membrane potential of Trypanosoma brucei bloodstream and procyclic trypomastigotes mitochondria in situ. At similarly high concentrations (> 10 microM), thapsigargin was also found to release Ca2+ and collapse the membrane potential of isolated rat liver mitochondria. These results indicate that care should be taken when attributing the effects of thapsigargin in intact cells to the specific inhibition of the sarcoplasmic and endoplasmic reticulum Ca(2+)-ATPase family of calcium pumps. In addition, we have found no evidence for an increase in intracellular Ca2+ by release of the ion from intracellular stores by nigericin, measuring changes in cytosolic Ca2+ by dual wavelength spectrofluorometry in fura-2-loaded T. brucei bloodstream trypomastigotes or measuring Ca2+ transport in digitonin permeabilized cells. PMID- 8473302 TI - Cholesterol loading of macrophages leads to marked enhancement of native lipoprotein(a) and apoprotein(a) internalization and degradation. AB - Lipoprotein(a) levels in the plasma are strongly correlated with atherosclerotic coronary artery disease. Although the mechanism of this effect is not known, the interaction of lipoprotein(a) with macrophages may be important. Previous work has shown that macrophages in culture internalize and degrade native lipoprotein(a) poorly. In the present study, the interaction of Lp(a) with mouse peritoneal and human monocyte-derived macrophages that were cholesterol-loaded, such as occur in atheromata, was investigated. 125I-Lp(a) degradation was increased 4-5-fold in macrophages that had been loaded with cholesterol by incubation with acetyl-LDL for 2-4 days. The enhanced degradation of Lp(a) by foam cells was chloroquine-sensitive and dependent upon the presence of calcium in the extracellular medium. Incubation of the macrophages with acetyl-LDL plus an inhibitor of acyl CoA:cholesterol acyltransferase, which increased the free cholesterol content and decreased the cholesteryl ester content of the cells, resulted in an even greater up-regulation of 125I-Lp(a) degradation (8-23-fold over control macrophages). The interaction of Lp(a) with cholesterol-loaded macrophages involved the apoprotein(a) moiety of Lp(a) since 125I-apoprotein(a), but not 125I-Lp(a-), was degraded to a much greater extent by foam cells compared to control macrophages. The uptake and degradation of Lp(a) in foam cells was not mediated by LDL, scavenger, LDL receptor-related protein (LRP), or plasminogen receptors. Thus, cholesterol loading of macrophages markedly enhances the internalization and lysosomal degradation of Lp(a) and apo(a) by a calcium dependent receptor activity different from known lipoprotein receptors. PMID- 8473303 TI - Fibrin affinity of urokinase-type plasminogen activator. Evidence that Zn2+ mediates strong and specific interaction of single-chain urokinase with fibrin. AB - Interactions of components of the fibrinolytic system with fibrin play a key role in localization and regulation of plasminogen activation at the clot surface. Although interaction of tissue plasminogen activator (tPA) with fibrin is well established, the prevailing view is that urokinase-type plasminogen activator (uPA) does not bind to fibrin. In this report, I show that although there is little or no interaction of single-chain urokinase (Sc-uPA), two-chain urokinase (Tc-uPA), or low molecular weight urokinase (LMW-uPA) with fibrin in the absence of divalent metal cations, Sc-uPA is effectively bound to fibrin in the presence of Zn2+. By comparison, Tc-uPA is poorly bound and LMW-uPA is not bound to fibrin in the presence of the metal ion. The Zn(2+)-mediated fibrin binding of Sc-uPA is reversible, specific, and saturable. The interaction involves a single class of binding site with dissociation constant of 0.3 microM and stoichiometry of 2.7. Lacking apparent affinity for fibrin, uPA has not been considered to play a role in physiological fibrinolysis. The present study conclusively shows that Sc-uPA possesses a latent affinity for fibrin that is expressed in the presence of Zn2+. These findings raise the possibility that Zn2+ plays a regulatory role in uPA mediated fibrinolysis by promoting effective localization of Sc-uPA at the clot surface. PMID- 8473304 TI - 1H NMR-based determination of the three-dimensional structure of the human plasma fibronectin fragment containing inter-chain disulfide bonds. AB - Human plasma fibronectin is a plasma glycoprotein that plays an important role in many biological processes. It consists of two identical 230-250-kDa subunits that are joined by two disulfide bonds near their carboxyl termini. Each subunit contains various binding domains composed of three types of homologous repeats. Recent work has determined the three-dimensional structures of various repeat fragments, but little is known about the three-dimensional structure of the carboxyl-terminal region. A recent NMR study of a plasmin-digested carboxyl terminal inter-chain disulfide-linked heptapeptide dimer has proposed that the two subunits are arranged in an antiparallel fashion (An et al. (1992) Biochemistry 31, 9927-9933). We have now determined the three-dimensional structure for a substantial portion of a trypsin-digested interchain disulfide linked 52-residue (6 kDa) fragment of the carboxyl-terminal of human plasma fibronectin (which includes the above-mentioned heptapeptide dimer) using two dimensional NMR methods and a new strategy for NMR-based protein structure determination. The NMR data requires that the two chains in the dimer be linked in a symmetric, antiparallel arrangement. The resulting monomer conformation consists of two twisted or coiled segments, Thr3-Asn6 and Ile9-Phe12, connected by the Cys7-Pro8 residues in extended conformations, with the two monomer chains cross-linked at residues Cys7 and Cys11. The conformation of the heptapeptide dimer region differs substantially from the conformation proposed by An et al. PMID- 8473305 TI - Isolation, sequence analysis, and cloning of haemadin. An anticoagulant peptide from the Indian leech. AB - A slow, tight-binding inhibitor of thrombin with an apparent molecular mass of about 5 kDa has been isolated from Haemadipsa sylvestris, an Indian leech of the family of Haemadipsidae. The inhibitory activity, called haemadin, is thrombin specific since it does not inhibit other proteases like trypsin, chymotrypsin, factor Xa, or plasmin. NH2-terminal amino acid sequence analysis (residues 1-45) does not reveal any homology to known serine protease inhibitors, including the thrombin-specific inhibitor hirudin. The haemadin cDNA cloned by polymerase chain reaction techniques codes for a polypeptide of 57 amino acid residues preceded by 20 residues of a signal peptide sequence. A synthetic gene coding for the mature haemadin was expressed in Escherichia coli. Recombinant haemadin displays a similar inhibition constant and specific activity as its natural counterpart. Although there is no obvious sequence identity between haemadin and hirudin, both proteins seem to share common mechanisms for thrombin inhibition. PMID- 8473306 TI - The effect of activated protein C on fibrinolysis in cell-free plasma can be attributed specifically to attenuation of prothrombin activation. AB - The effect of human activated protein C (APC) on tissue plasminogen activator (tPA)-induced fibrinolysis was studied in cell free plasma and in a system of purified components. Clots were produced by adding plasma or a solution of fibrinogen and plasminogen to the wells of a microtiter plate containing small separated aliquots of Ca2+, thrombin, and tPA, plus and minus APC. Initial clotting and subsequent fibrinolysis were monitored continuously by turbidity. The lysis time of dialyzed normal human plasma (NHP) was longer than that of dialyzed barium citrate-adsorbed plasma (BAP). APC had no effect on the lysis time of BAP but shortened the lysis time of NHP to that of BAP. Two fractions were produced from material eluted from the barium citrate pellet by precipitation of selective components with polyethylene glycol 8000 (PEG). One fraction comprised materials which precipitated at 5% PEG (5% PF) and the other materials which precipitated between 5 and 40% PEG (5-40% PF). Both fractions together, but neither alone, prolonged the lysis time of BAP, an effect which could be reversed by APC. Fractionation of the 5% PF showed that the component with the required activity has properties of the procoagulant surface and can be replaced with vesicles of phosphatidylcholine/phosphatidylserine (PCPS). In addition, the 5-40% PF can be replaced with either the combination of purified coagulation Factors II, IX, and X or Factor II plus the prothrombin activator Factor Xa. When Factor Xa was used as the activator in BAP plus PSPC vesicles, a dose-dependent saturable increase in lysis time was observed with a half-maximal increase occurring at 32 pM Factor Xa. This effect was eliminated by APC. In a system of purified components comprising PCPS vesicles, Factors V and II, protein S, plasminogen and fibrinogen; the prothrombin activators Factor Xa and ecarin both induced a prolongation of the lysis time. APC prevented prolongation by Factor Xa but not by ecarin. The time courses of the generation of thrombin and plasmin during fibrinolysis of clots produced from systems of purified components in the presence and absence of APC, and with Factor Xa as the prothrombin activator, were determined by standardized activity assays using chromogenic substrates. In the absence of APC the lysis time was 145 min, and prothrombin was quantitatively converted to thrombin. In the presence of APC, however, the lysis time was reduced to 100 min with no evidence for the activation of prothrombin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8473307 TI - Determination of the DNA bend angle induced by the restriction endonuclease EcoRV in the presence of Mg2+. AB - We have used the method of Zinkel and Crothers (Zinkel, S.S., and Crothers, D.M. (1990) Biopolymers 29, 29-38) to determine the degree of bending induced by the binding of the restriction endonuclease EcoRV to its recognition sequence ( GATATC-). A set of four calibration DNA fragments was constructed that contained zero, two, four, or six phased A-tracts in their centers and an EcoRV site at the 5'-end to account for the electrophoretic influence of the bound protein. The mobilities of these calibration molecules complexed with EcoRV were compared to that of a test DNA containing a central EcoRV site also complexed with EcoRV. The EcoRV-induced bend angle was found to be 44 degrees +/- 4 degrees. These experiments were performed with a catalytically inactive EcoRV mutant that still binds DNA specifically in the presence of Mg2+. In the absence of Mg2+, which is necessary for specific binding, there is no difference in the mobilities of the fragments with a peripheral or a central EcoRV site complexed with EcoRV, indicating that nonspecific binding on average does not lead to measurable DNA bending. PMID- 8473308 TI - The function and distinctive regulation of the integrin VLA-3 in cell adhesion, spreading, and homotypic cell aggregation. AB - To assess directly the functional role of the integrin VLA-3 (alpha 3 beta 1), we transfected human alpha 3 cDNA into erythroleukemia (K562) cells and rhabdomyosarcoma (RD) cells. The resulting transfectants (KA3 and RA3) expressed alpha 3 beta 1 on the cell surface as confirmed using a panel of nine anti-alpha 3 monoclonal antibodies. Neither of the transfected cells exhibited increased adhesion to the extracellular matrix proteins fibronectin, laminin, and collagen. However, the KA3 transfectants did bind strongly to the extracellular matrix deposited by epidermal and carcinoma cell lines, allowing the cells to attach and spread. Binding to this cell-deposited ligand, probably containing epiligrin/kalinin, was specific to VLA-3 and could be inhibited by anti-alpha 3 antibodies and by EDTA, but not by RGD peptides. In marked contrast to other integrins (VLA-2 and VLA-4), VLA-3 showed high constitutive activity in K562 cells, but was minimally active in RD cells. Also contrasting with other beta 1 integrins, VLA-3 was minimally stimulated by the anti-beta 1 monoclonal antibody TS/216 under normal conditions. VLA-3-mediated adhesive function was well supported by either Mg2+ or Mn2+, but was almost completely abolished by the presence of 1 mM Ca2+. Surprisingly, this negative Ca2+ effect was completely overcome by the addition of the stimulatory anti-beta 1 monoclonal antibody TS2/16. Together, these results point to markedly distinct regulation for VLA-3 function compared to other beta 1 integrins. Also, all anti-VLA-3 antibodies were able to induce temperature-dependent homotypic cell aggregation of KA3 cells, but not K562 cells. However, this aggregation did not appear to be directly mediated by VLA-3 since it was not inhibited by EDTA. In addition, no enhancement of heterotypic cell-cell adhesion was observed in alpha 3-transfected cells. PMID- 8473309 TI - Saccharomyces cerevisiae elongation factor 2. Mutagenesis of the histidine precursor of diphthamide yields a functional protein that is resistant to diphtheria toxin. AB - Protein synthesis elongation factor 2 (EF-2) is the target of the ADP ribosylating activity of diphtheria toxin which is responsible for cell killing. Diphthamide, an unique post-translationally modified histidine residue, is both required for and the site of this ADP-ribosylation. Although present in the EF-2 of all eukaryotes and archaebacteria, the function of diphthamide is unknown. Here we describe the site-specific mutagenesis of the histidine precursor of diphthamide, histidine 699, in yeast EF-2. Plasmid-borne EFT was randomly mutagenized at the histidine 699 codon, and the technique of plasmid shuffling was utilized to select strains that were maintained by the mutant EFT. These mutants were screened for diphtheria toxin resistance. Sequence analysis of the EFT in 49 toxin-resistant isolates showed that histidine 699 had been replaced by 1 of 4 amino acids: asparagine, glutamine, leucine, or methionine. All 11 of the possible codons corresponding to these 4 amino acids were found. The growth rates of cells sustained by the mutant forms of EF-2 were slightly slower than those of isogenic wild-type cells. We conclude that despite its strict conservation and universal post-translational modification, the histidine precursor of diphthamide is not essential to the function of yeast EF-2 in protein synthesis. PMID- 8473310 TI - Reversible palmitoylation of the protein-tyrosine kinase p56lck. AB - The myristoylated protein-tyrosine kinase, p56lck, is expressed predominantly in T cells where it is believed to play a role in T cell activation. We observed a 56-kDa protein that became metabolically labeled in intact T lymphoid cells that were incubated with either [3H]myristate or [3H]palmitate. This protein was identified as p56lck based on its specific immunoprecipitation with polyclonal antisera to p56lck, by induction of a shift in its electrophoretic mobility following treatment of cells with 12-O-tetradecanoylphorbol-13-acetate and by co chromatography with p56lck on protamine-agarose. Characterization of the two acylation events revealed that, in contrast to the p56lck-associated radioactivity from [3H]myristate-labeled cells, the p56lck-associated radioactivity from [3H]palmitate-labeled cells was susceptible to cleavage by neutral hydroxylamine and was not blocked by inhibitors of protein synthesis. Pulse-chase analyses revealed that the labeling of p56lck with [3H]palmitate, but not [3H]myristate, was reversible. The presence of covalently attached palmitate on p56lck from [3H]palmitate-labeled cells was verified by thin-layer chromatography following acid hydrolysis of the acylated protein. 2 Hydroxymyristate, which is metabolically activated to form a potent inhibitor of protein myristoylation, specifically inhibited the acylation of p56lck with [3H]myristate without affecting its labeling with [3H]palmitate. These studies indicate that p56lck is both a cotranslationally myristoylated and post translationally palmitoylated protein. PMID- 8473311 TI - In organello footprinting. Analysis of protein binding at regulatory regions in bovine mitochondrial DNA. AB - Detailed study of mammalian mitochondrial transcriptional and replicative mechanisms is currently limited to in vitro analyses, requiring isolation and reassembly of functional components to mimic the in vivo process. To complement these studies and begin understanding the intracellular function of mitochondrial DNA (mtDNA) regulatory regions, we developed in organello footprinting to investigate protein-DNA interactions within the mitochondrion. Using a methylation protection technique and mitochondria isolated from bovine brain tissue, we analyzed five domains believed critical for regulating mtDNA function. Near equivalent protein-DNA interactions were seen upstream of both light and heavy strand RNA start sites at positions consistent with those observed for human mitochondrial transcription factor 1 DNA binding in vitro. Downstream of the 16 S rRNA gene, a high level of protein occupancy was detected within the bovine homologue of the human tridecamer sequence required for attenuation of transcription in vitro. Immediately upstream of the origin of heavy strand replication, a novel site of protein-mtDNA interaction was observed within conserved sequence block 1, suggesting its potential as a regulatory element involved in initiation of heavy strand DNA synthesis. Unlike regions associated with the origin of heavy strand replication, protein-mtDNA interaction was not detected at the origin of light strand replication or within flanking tRNA genes. PMID- 8473312 TI - Nucleotide binding to actin. Cation dependence of nucleotide dissociation and exchange rates. AB - We have reinvestigated nucleotide binding to actin in order to resolve conflicts regarding the mechanism of nucleotide dissociation and exchange. We present evidence that supports a mechanism for nucleotide binding to actin in which the tightly bound divalent cation (Ca2+ or Mg2+) directly interacts with the bound nucleotide. The dissociation rates of ATP or ADP from actin are limited by the dissociation of the high affinity divalent cation from actin and vary inversely with free Ca2+ or free Mg2+ concentration. The divalent cation concentration range over which attenuation of the ATP dissociation takes place is about 100 fold greater for Mg2+ than that for Ca2+ due to the much slower association rate constant for Mg2+ compared with Ca2+. The relative affinity for ATP versus ADP is 200:1 for Ca-actin in 100 microM free [Ca2+], and 4:1 for Mg-actin in 100 microM free [Mg2+]. Actin without a tightly bound divalent cation has about a 3-fold greater affinity for ATP than ADP. At constant free divalent cation concentration, the rate of nucleotide exchange on actin is described by competitive binding kinetics. PMID- 8473313 TI - G protein-mediated inhibition of phospholipase C activity in a solubilized membrane preparation. AB - In solubilized bovine brain membrane preparations AlF4- (20 microM AlCl3 plus 10 mM NaF) and 50 nM guanosine 5-O-(2-thiotriphosphate) (GTP gamma S) promoted a rapid but transient inhibition of phospholipase C (PLC) activity. Maximal inhibition was evident within 7 min of incubation, followed by reversal of inhibition. In contrast, 10 microM GTP gamma S did not induce inhibition of PLC activity but rather produced a time-dependent stimulation of PLC activity. GTP gamma S-dependent inhibition of PLC activity was concentration-dependent with half-maximal inhibition at 1 nM. Inhibition was antagonized by guanosine 5-O-(2 thiodiphosphate (GDP beta S). Pertussis toxin delayed the onset of inhibition by GTP gamma S but did not prevent the inhibitory effect. alpha o-GTP gamma S or alpha o-GDP had little effect on PLC activity. alpha i-GTP gamma S and alpha i GDP produced a 15% inhibition of PLC activity. Beta gamma subunits did not inhibit basal PLC activity but did attenuate the net degree of inhibition due to GTP gamma S. Inhibition was associated with a decrease in the Ca2+ sensitivity of PLC. Preincubation of membranes with anti-PLC-beta 1 antibody, but not anti-PLC gamma 1 or anti-PLC-delta 1, prevented the GTP gamma S-mediated inhibition of PLC. These studies implicate PLC-beta 1 as an effector system that is under negative modulation by a G protein-dependent mechanism. PMID- 8473314 TI - Phosphorylation of HIV-1 gag proteins by protein kinase C. AB - We have demonstrated that the 17-kDa N-terminal matrix protein (p17gag) of HIV-1 Pr55gag is a substrate for protein kinase C (PKC). Phosphorylation of p17gag and Pr55gag was studied in vivo by infecting COS-7 cells with a recombinant vaccinia virus containing the HIV-1 gag-pol gene. Basal gag protein phosphorylation was inhibited up to 75% with the PKC inhibitor, H-7, and stimulated 3-4-fold with phorbol 12-myristate 13-acetate. In experiments using MCF-7 cell lines, p17gag and Pr55gag were dramatically phosphorylated only in clones with high PKC activity. Bacterially expressed and purified non-myristoylated and N myristoylated p17gag were efficiently phosphorylated in a Ca2+ and phosphatidylserine-dependent manner by purified PKC. The N-myristoylated p17gag exhibited an apparent Km = 4 microM for PKC phosphorylation. Both in vitro and in vivo phosphorylated p17gag yielded identical V8 protease digestion phosphopeptide maps, indicating identical PKC phosphorylation sites. Phosphoamino acid analysis of the in vitro phosphorylated p17gag revealed only phosphoserine. These data are consistent with the identification of a highly conserved consensus PKC phosphorylation site motif in the HIV-1 gag protein at Ser111 and suggests that PKC phosphorylation plays an important role in gag protein function. PMID- 8473315 TI - Inhibitory properties of full-length and truncated recombinant tissue factor pathway inhibitor (TFPI). Evidence that the third Kunitz-type domain of TFPI is not essential for the inhibition of factor VIIa-tissue factor complexes on cell surfaces. AB - Human tissue factor pathway inhibitor (TFPI) is a plasma protease inhibitor that consists of three tandem Kunitz-type inhibitor domains flanked by a negatively charged NH2 terminus and a positively charged COOH-terminal tail. Previous studies have shown that the first and second Kunitz-type domains in TFPI are involved in the inhibition of factor VIIa and factor Xa activity, respectively. In the present study, we have compared the inhibitory properties of full-length recombinant TFPI and a truncated form of TFPI lacking the third Kunitz-type domain and COOH-terminal tail (TFPI1-161) with respect to inhibition of factor VIIa-tissue factor complexes on the surface of a human bladder carcinoma cell line J82. Full-length TFPI and TFPI1-161 were kinetically indistinguishable with respect to neutralization of the proteolytic activity of preformed complexes of factor VIIa-tissue factor on the J82 cell surface in the absence of factor Xa. Equimolar amounts of factor Xa augmented the anticoagulant activity of both preparations of TFPI to the same extent, and both preparations of TFPI were equally effective in inhibiting factor VIIa-tissue factor amidolytic activity in solution phase. In addition, plasma concentrations of both forms of TFPI, in stoichiometric complex with factor Xa, inhibited cell surface factor VIIa-tissue factor proteolytic activity markedly faster than plasma levels of antithrombin III, even in the presence of 1 unit/ml heparin. The results of displacement studies suggested slight differences in the affinity of the two TFPI molecules for the cell surface in that approximately 5% of a VIIa.TF.Xa.TFPI1-161 quaternary complex on J82 cells was displaceable from the cell surface by high concentrations of factor VIIa (10-100 nM), whereas only 1-2% of a VIIa.TF.Xa.TFPI complex was displaceable under comparable conditions. Pretreatment of the cells with TFPI/Xa alone or together with R152E factor VII, followed by factor VIIa treatment, revealed significant differences in the two TFPI forms with respect to the degree with which offered factor VIIa could restore factor X activation on the cell surface. These differences notwithstanding, our collective findings indicate that the third Kunitz-type domain and/or COOH-terminal tail of TFPI is not essential for the inhibition of cell surface factor VIIa-tissue factor complexes and suggests that TFPI1-161 may be a useful therapeutic agent in the treatment of thromboembolic episodes. PMID- 8473316 TI - Mutagenic analysis of AMP nucleosidase from Escherichia coli. Deletion of a region similar to AMP deaminase and peptide characterization by mass spectrometry. AB - AMP nucleosidase (EC 3.2.2.4) from Escherichia coli and AMP deaminase (EC 3.5.4.6) from bakers' yeast are proposed to regulate cellular AMP levels under allosteric control of the activator ATP and the inhibitor, PO4. Both enzymes contain catalytic sites which bind AMP and regulatory sites which bind ATP. The deduced amino acid sequences of the proteins revealed only one region of homology in which six of eight amino acids are identical. A similar sequence is found in glyceraldehyde-3-phosphate dehydrogenase, phoE, ras proteins, RNA polymerase, K(+)-ATPase, nucleolin, and other proteins expected to have nucleotide or phosphate binding properties. In the crystal structure of glyceraldehyde-3 phosphate dehydrogenase, this sequence is part of the NAD(+)-binding site. The function of these amino acids was explored with a deletion mutant of AMP nucleosidase. The protein was over-produced in a pTZ construct using the AMP nucleosidase promoter which resulted in approximately 30% of the total protein as the desired enzyme. The mutation was characterized by DNA sequence analysis and by direct analysis of the peptides using high performance liquid chromatography mass spectrometry. Deletion of amino acids 128-135, corresponding to DGSELTLD, produced an enzyme with a 20-fold decrease in Vmax but with smaller changes in substrate saturation kinetics, activation by MgATP, inhibition by inorganic phosphate, and inhibition by the tight-binding inhibitor, formycin 5-phosphate. The deletion mutant of AMP nucleosidase exhibits hysteresis in establishing a steady-state rate of product formation which is most pronounced in the absence of MgATP. These results establish that the sequence DGSELTLD in E. coli AMP nucleosidase is not required for binding of AMP, MgATP, or inorganic phosphate. However, the mutant enzyme has a structural defect related to the polymerization state which delays the onset of catalysis and decreases the catalytic efficiency. PMID- 8473317 TI - Lysine 87 in the beta subunit of tryptophan synthase that forms an internal aldimine with pyridoxal phosphate serves critical roles in transimination, catalysis, and product release. AB - This study provides valuable insights into the functions of the lysine residue that forms an internal aldimine with pyridoxal phosphate in the beta subunit of tryptophan synthase from Salmonella typhimurium. Our spectroscopic and kinetic studies demonstrate that a mutant alpha 2 beta 2 complex having beta subunit lysine 87 replaced by threonine forms external aldimines with several amino acids including L-serine, beta-chloro-1-alanine, L-tryptophan, and D-tryptophan. Because the rates of aldimine formation are very slow, we conclude that one role of lysine 87 in the wild type enzyme is to facilitate formation of external aldimines by transimination. Lysine 87 is an essential catalytic residue because the mutant alpha 2 beta 2 complex has no measurable activity in reactions catalyzed by the beta subunit and does not convert external aldimines to products. The mutant enzyme carries out two slow partial beta-elimination reactions: the conversion of beta-chloro-L-alanine and L-serine to enzyme-bound aminoacrylate. The reaction with L-serine is catalyzed by ammonia, which partially replaces the deleted epsilon-amino group. Lysine 87 is important for substrate and product release because L-serine, L-tryptophan, and aminoacrylate dissociate very slowly from the mutant alpha 2 beta 2 complex. Our ability to prepare very stable derivatives of the mutant alpha 2 beta 2 complex containing tightly bound aldimines with a substrate, a product, or a reaction intermediate provides valuable materials for ongoing x-ray crystallographic investigations and future kinetic analyses of the allosteric activation of the alpha subunit by beta subunit ligands. PMID- 8473318 TI - Characterization of the purified vitamin K-dependent gamma-glutamyl carboxylase. AB - Vitamin K-dependent carboxylase, purified from bovine liver, has properties similar to those reported for the carboxylase activity present in crude, solubilized microsomes. The purified carboxylase was found to possess the vitamin K epoxidase activity, believed to be essential for vitamin K-dependent carboxylation, but did not contain vitamin K epoxide reductase activity. Kinetic studies of the carboxylase done under defined conditions were complicated by the non-Michaelis-Menten kinetic behavior observed for reactions with two of the enzymes substrates, FLEEL and vitamin K1 hydroquinone. Initial rate experiments with the substrate FLEEL demonstrated behavior consistent with substrate inhibition and gave half-maximal activity at 1 mM FLEEL. Experiments with the substrate vitamin K1 hydroquinone also displayed non-Michaelis-Menten kinetics, as maximal activity was reached prematurely in relation to behavior at lower concentrations. Half-maximal activity was observed at 35 microM vitamin K1 hydroquinone. Initial rate experiments with varying NaH14CO3 concentration displayed Michaelis-Menten kinetics and gave a Km(app) of 0.29 mM. At cosubstrate concentrations chosen to obtain near-maximal activity, initial rate studies with varying NaH14CO3 concentration indicated a kcat near 1.0 s-1. Removal of the fourth substrate, oxygen, resulted in the loss of more than 99% of carboxylase activity. The sulfhydryl reagent N-ethylmaleimide inhibited carboxylase irreversibly, as did the anticoagulant warfarin. PMID- 8473319 TI - Dityrosine and tyrosine oxidation products are endogenous markers for the selective proteolysis of oxidatively modified red blood cell hemoglobin by (the 19 S) proteasome. AB - Cells exposed to oxidative stress have been shown previously to exhibit both protein oxidation and increased proteolysis. Experiments conducted with purified proteins in vitro have indicated that oxidatively modified proteins may be selectively degraded by intracellular proteases, but a definitive cause-and effect relationship has not been demonstrated previously in intact cells. Several investigators have proposed that oxidatively modified proteins are selectively degraded within cells, but the possibility that oxidants may activate intracellular proteases (directly or indirectly) to catalyze the indiscriminate degradation of undamaged proteins has not been discounted. Armed with the knowledge that dityrosine is a specific product of protein oxidation, we undertook a series of experiments to test the hypothesis that oxidized proteins undergo selective intracellular degradation. Our results demonstrate that dityrosine is produced in the hemoglobin molecule when red blood cells are exposed to a continuous flux of hydrogen peroxide (H2O2). The dityrosine so produced is only released from the hemoglobin by proteolysis and is stable to prolonged incubation with cell extracts. Inhibitors of proteolysis have no effect on dityrosine production but do effectively prevent dityrosine release. Proteasome (the 670-kDa multicatalytic proteinase complex, that we have previously called macroxyproteinase or MOP (Pacifici, R. E., Salo, D. C., and Davies, K. J. A. (1989) Free Radical Biol. & Med. 7, 521-526; Salo, D. C., Pacifici, R. E., Lin, S. W., Giulivi, C., and Davies, K. J. A. (1990) J. Biol. Chem. 265, 11919-11927; Pacifici, R. E., and Davies, K. J. A. (1991) Gerontology 37, 166-180) appears responsible for dityrosine release during the selective degradation of oxidatively modified proteins in red blood cells and red cell extracts. We conclude that the elevated rates of proteolysis observed in response to oxidative stress do, indeed, reflect selective degradation of oxidatively modified (damaged) proteins. Despite a relatively low production rate, dityrosine has a high fluorometric quantum yield and is, of course, a specific product of protein oxidation. As an apparently stable metabolic end product, dityrosine may prove to be an extremely valuable (cellular or urinary) marker or index of organismal oxidative stress. PMID- 8473321 TI - Triacylglycerol synthesis by an sn-1,2(2,3)-diacylglycerol transacylase from rat intestinal microsomes. AB - A membrane-associated sn-1,2(2,3)-diacylglycerol transacylase activity was purified 550-fold from the microsomes of rat intestinal villus cells. The enzyme was solubilized with the zwitterionic detergent 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate and was isolated and purified by sequential chromatography on hydroxylapatite, an anion exchanger, Affi-Gel heparin and Cibacron blue A-agarose. SDS-polyacrylamide gel electrophoresis revealed two major closely migrating polypeptides of apparent molecular mass of 50 and 52 kDa. Incubation of the isolated enzyme with sn-1,2(2,3)dioleoyl-[2 3H]glycerol yielded trioleoyl[2-3H]glycerol and 2-oleoyl[2-3H]glycerol. The synthesis of triacylglycerols was independent of acyl-CoA, as indicated by the absence of incorporation of radioactivity from [1-14C]oleoyl-CoA into mono-, di-, or triacylglycerols under these conditions. The transacylase did not hydrolyze triacylglycerols readily and was not affected by the acyltransferase inhibitors, N-ethylmaleimide and 4,4'-diisothiocyanostilbene-2,2'-disulfonate, while the lipase/hydrolase inhibitors NaF, phenylmethylsulfonyl fluoride, and diethyl p nitrophenyl phosphate caused partial inactivation. The enzyme was specific toward 1(3)-positions of rac 1,2-diacylglycerols but did not utilize the -1,3 diacylglycerols or other neutral lipid esters effectively and was not capable of removing fatty acids from phosphatidylcholine or of transfer of fatty acids from X (unspecified enantiomer)-1,2-diacylglycerol to lysophosphatidylcholine. Since the diacylglycerol transacylation did not lead to accumulation of either sn-1,2- or sn-2,3-diacylglycerols during incubation with the racemates, it is concluded that both sn-1,2- and sn-2,3-s are utilized at similar rates. PMID- 8473320 TI - Properties and regulation of the cell cycle-specific NIMA protein kinase of Aspergillus nidulans. AB - NIMA is the protein product of the nimA gene of the filamentous fungus Aspergillus nidulans, required for progression of cells from G2 into mitosis. The protein kinase activity of NIMA, assayed by phosphorylation of beta-casein, varies during the nuclear division cycle, reaching a maximum in late G2 and M. To investigate the biochemical properties of this cell cycle-regulated protein kinase, we have expressed nimA cDNA that encodes full-length NIMA in Escherichia coli as a fusion product with glutathione S-transferase. Purified NIMA phosphorylated beta-casein, with a Km of 38 microM and Vmax of 156 nmol/min/mg. NIMA also demonstrated a Km of 69 microM for ATP. Both recombinant and cellular NIMA kinases behaved as oligomers on gel filtration chromatography, and their kinase activities were strongly inhibited by various salts. By using both protein and peptide substrates, NIMA demonstrated a serine/threonine-specific protein kinase activity. Cellular NIMA exists as a phosphoprotein, and bacterially expressed NIMA was also phosphorylated on multiple serine/threonine residues. Some of these phosphorylations appeared essential for NIMA activity as the enzyme could be dephosphorylated and inactivated in vitro by protein serine/threonine phosphatases. Use of a kinase-negative mutant of NIMA revealed that the NIMA enzyme undergoes autophosphorylation when expressed at high concentrations in bacteria. Taken together, these data suggest that cellular mechanisms may exist to regulate the phosphorylation state and activity of the NIMA protein kinase during the nuclear division cycle in A. nidulans. PMID- 8473322 TI - ADP induces inositol phosphate-independent intracellular Ca2+ mobilization in brain capillary endothelial cells. AB - The action of adenine and uracyl nucleotides on rat brain capillary endothelial cells was investigated. ATP, UTP, and adenosine 5'-O-(3-thiotrisphosphate) activated phospholipase C and induced large increases in [Ca2+]i. ADP had a different action. At low concentrations (< 10 microM), ADP induced the mobilization of a thapsigargin-sensitive intracellular Ca2+ store in the absence of measurable production of inositol phosphates. At larger concentrations (> 30 microM), ADP activated phospholipase C. The actions of ATP and ADP and of UTP and ADP were additive. Those of ATP and UTP were not. In the presence of ATP or UTP, the dose-response curve for ADP action on [Ca2+]i was monophasic and corresponded to the high affinity responses. Finally, we observed that ADP did not desensitize cells to the actions of ATP and UTP. In contrast, cross-desensitization of the actions of ATP and UTP were observed. It is concluded that two types of receptors account for the actions of nucleotides: (i) a nucleotide that recognizes ATP and UTP and that is positively coupled to phospholipase C; and (ii) an ADP-specific receptor that induces the mobilization of a thapsigargin-sensitive intracellular Ca2+ pool in a manner independent of the formation of inositol phosphates. PMID- 8473323 TI - Characterization of the human ADP-ribosylation factor 3 promoter. Transcriptional regulation of a TATA-less promoter. AB - The 5'-flanking region of the human ADP-ribosylation factor 3 gene contains the features of a housekeeping gene. It lacks a TATA or CAAT box, has several GC boxes within a highly GC-rich region, and utilizes multiple transcription initiation sites. The cis-acting elements involved in regulating expression of the gene were identified by transient transfections of IMR-32 neuroblastoma cells. Reporter plasmids were modified to facilitate construction of defined promoter deletions linked to chloramphenicol acetyltransferase or luciferase using ligation-independent cloning. Transfection analyses indicated that sequences within 58 base pairs of the transcription initiation site were necessary for full expression, in particular a sequence containing the 10-base pair palindrome TCTCGCGAGA. Electrophoretic mobility shift assays performed with IMR-32 nuclear extracts demonstrated that a DNA-binding protein, termed TLTF, bound to an oligonucleotide containing this palindrome. Competition experiments showed that mutations within the core of the palindrome abolished in vitro binding and that the same protein bound to a 5'-proximal sequence. Expression of the promoter containing a mutated palindrome was reduced dramatically, consistent with the conclusion that this region functions in vivo to control expression of the ARF3 gene. PMID- 8473324 TI - ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP ribosylation factor domain. AB - Clones referred to as ARD 1 were isolated from human and rat cDNA libraries. ARD 1 genes encode a putative 64-kDa protein that contains an 18-kDa ADP-ribosylation factor (ARF) domain at the carboxyl terminus and is much larger than the other monomeric approximately 20-kDa guanine nucleotide-binding ARF proteins thus far identified. ARD 1 mRNAs of 3.7 and 4.1 kilobases were detected in all rat tissues as well as in mouse and rabbit brain, human fibroblasts, and human neuroblastoma cells but not in HL-60 cells. Based on sequence identities, ARD 1 is highly conserved between rat and human. The ARF domain of ARD 1 contains the consensus sequences believed to be involved in guanine nucleotide binding, which are conserved in the ARFs and other GTP-binding proteins. Recombinant ARD 1 or the ARF domain of ARD 1, which lacks the 15 amino acids corresponding to the amino terminal regions of ARFs stimulated, in a GTP-dependent manner, cholera toxin ADP ribosyltransferase activity in the presence of 0.3% Tween 20. It had no effect in the presence of SDS, dimyristoylphosphatidylcholine/cholate, or cardiolipin. These observations are consistent with the conclusion that the amino-terminal region of ARF proteins is not required for activation of cholera toxin. In addition, the characteristic features of ARF proteins may be found as domains of larger mammalian proteins. PMID- 8473325 TI - Identification of a new cell adhesion motif in two homologous peptides from the COOH-terminal cell binding domain of human thrombospondin. AB - Thrombospondin-1 (TS1) contains at least four domains that support cell attachment. The COOH-terminal cell binding domain (CBD) was first identified with a monoclonal antibody against TS1 that blocked secretion-dependent platelet aggregation. Subsequently, this domain of TS1 has been found to bind a number of normal and transformed cells. We have localized attachment sites for human melanoma cells (G361) within the CBD to two noncontiguous 30-residue peptides designated C4 and C7 (Kosfeld, M. D., and Frazier, W. A. (1991) J. Biol. Chem. 267, 16230-16236). Here we report studies to define the active sequences within C4 and C7. An octapeptide, RFYVVMWK (4N1-1), from C4 and a pentapeptide, IRVVM (7N3-1), from C7 were found to support attachment of G361 melanomas, K562 erythroleukemia cells, HT1080 fibrosarcomas, C32 amelanotic melanomas, and endothelial cells. These peptides also inhibit the adhesion of cells to the recombinant CBD of TS1. The hexapeptide RFYVVM (4N1-2) also inhibits cell attachment. The inhibitory effect of combinations of C4- and C7-derived peptides is synergistic. The sequences 4N1-1 and 7N3-1 of TS1 share homology with two cell adhesive peptides from laminin (LM), LMF9 and LMPA22-2, respectively. These TS1 and LM peptides are interchangeable in inhibiting the adhesion of G361 cells to LM or TS1, suggesting a possible sharing of receptors by LM and TS1. K562 cells, however, bound only to TS1, and this binding was inhibited preferentially by the TS1 CBD peptides, indicating a receptor specific for TS1 which does not recognize LM. The active TS1 peptides are highly conserved among five species and four isoforms of TS1. Homologs of the TS1 peptides are found in tenascin, a matrix protein that shares several properties with TS1 and in factor VIII, alpha 2 macroglobulin, and von Willebrand factor. PMID- 8473326 TI - Membrane binding kinetics of factor VIII indicate a complex binding process. AB - Factor VIII functions as a component of the tenase enzyme complex upon phospholipid membranes. Factor VIII binds to phosphatidylserine-containing membranes and apparently provides high affinity binding sites for factor IXa upon these membranes. We have characterized the binding kinetics of human factor VIII with phosphatidylserine-containing membranes and directly compared the measured properties with those of factor V. The initial phase of association was evaluated in a stopped-flow apparatus by fluorescence energy transfer from aromatic residues in the protein to dansyl-labeled phosphatidylethanolamine in the vesicles. Association proceeded at an apparent second-order rate of 0.12 microM-1 s-1 for extruded phospholipid vesicles and 0.42 microM-1 s-1 for sonicated vesicles under pseudo-first-order conditions in which the phospholipid concentration determined the rate. Increased temperature resulted in more rapid association, and the effect decreased in the order extruded vesicles > sonicated vesicles > extruded vesicles of dioleoylphospholipids, indicating that the structure of the phospholipid membrane contributes to the activation energy of binding. The binding of fluorescein-labeled factor VIII to membranes supported on glass microspheres (lipospheres) was monitored by flow cytometry. Under conditions in which the factor VIII concentration determined the rate there was rapid initial association at 6.9 microM-1 s-1, accounting for half of the bound factor VIII, and a slower component of 0.87 microM-1 s-1, accounting for the other half. Likewise, the dissociation of factor VIII from liposphere membranes was biphasic with a faster component of 0.010 s-1 and a slower component of 0.0012 s-1. Rates of association and dissociation for factor V were similar to those for factor VIII and were biphasic. These results allow estimation of the size of the phospholipid sites that interact with factors VIII and V and suggest that both proteins bind to membranes via a multistep process in which rapid association is followed by a slower step yielding higher affinity binding. PMID- 8473327 TI - Cloning of type XVII collagen. Complementary and genomic DNA sequences of mouse 180-kilodalton bullous pemphigoid antigen (BPAG2) predict an interrupted collagenous domain, a transmembrane segment, and unusual features in the 5'-end of the gene and the 3'-untranslated region of the mRNA. AB - Thus far, 16 distinct vertebrate collagens (types I-XVI) have been delineated. In this study, we have cloned a mouse collagenous protein, the 180-kDa bullous pemphigoid antigen (BPAG2). Isolation of over-lapping clones, together with 5' and 3' rapid amplification of cDNA ends, allowed delineation of the entire coding sequence. The 5' and 3' ends of the mRNA transcripts were confirmed by primer extension and anchored reverse transcription polymerase chain reaction analyses. The deduced polypeptide contained 1,433 amino acids, including a collagenous domain that consisted of 13 separate segments. Computer analysis of the deduced amino acid sequence demonstrated the presence of a membrane-associated segment. Examination of the 5' end of the BPAG2 gene revealed that the 295-base pair (bp) exon 1 contained two segments of (T)13AA and TT(A)11, whereas exon 2 was shown to contain the translation initiation codon. The 3' end of the mRNA transcript identified two 6-bp inverted repeat sequences that could form a stem for a 30-bp hairpin loop followed by a series of U residues. Comparison of mouse and human BPAG2 sequences demonstrated 86% homology and the unit of evolutionary period of 4.2 million years. In summary, we have cloned full-length mouse BPAG2 cDNA sequences that encode a collagenous polypeptide. We propose that this polypeptide be designated as the alpha 1-chain of type XVII collagen. PMID- 8473328 TI - Molecular cloning and genomic organization of a gene for luciferin-binding protein from the dinoflagellate Gonyaulax polyedra. AB - The circadian expressed luciferin-binding protein (LBP) gene from the marine bioluminescent alga Gonyaulax polyedra represents the first dinoflagellate gene that has been cloned and sequenced at both cDNA and genomic levels. Starting with a fragment from the 3'-end of the LBP cDNA that was found by immunoscreening of a cDNA library, genomic clones were obtained by the inverse polymerase chain reaction technique. Full-length cDNA clones were selected by screening a cDNA library by plaque hybridizations and by polymerase chain reaction amplifications. The LBP sequence has a 2004-nucleotide open reading frame coding for a protein of 668 amino acids (approximately 75 kDa). The reading frame and identity of the clone were confirmed by the sequence of an octapeptide obtained from a purified fragment of CNBr-treated LBP. A variant LBP cDNA was found to differ in sequence by approximately 11% at the DNA level. The untranslated regions of the mRNA are 111 nucleotides (5'-untranslated region) and 158 nucleotides (3'-untranslated region) long, respectively. The LBP gene contains no introns and exhibits certain features not typical for a eukaryotic gene. Its promoter does not include the typical TATA box within approximately 50 nucleotides upstream of the transcription start site, and the usual poly(A+) signal (AAUAAA) is not present on the end of the LBP mRNA. The copy number of the gene is very high (approximately 1000 copies/cell). However, the universal genetic code and conserved positions relevant for the translational apparatus are maintained. PMID- 8473329 TI - RNR-1, a nuclear receptor in the NGFI-B/Nur77 family that is rapidly induced in regenerating liver. AB - Liver regeneration following partial hepatectomy provides one of the few systems for analysis of mitogenesis in the fully developed, intact animal. Immediate early growth response genes, induced in the absence of prior protein synthesis, play an important regulatory role in the regenerative process. During screening of a subtracted cDNA library of immediate-early genes induced during liver regeneration, a novel member of the thyroid/steroid receptor superfamily, RNR-1 (regenerating liver nuclear receptor), was identified. This gene is not expressed in quiescent liver but is rapidly induced following partial hepatectomy and is specific to hepatic growth as it is not induced in other mitogen-treated cells. RNR-1 is also expressed in brain. A full-length cDNA clone of RNR-1 encodes a 66 kDa, 597-amino acid protein as verified by in vitro translation in reticulocyte lysate. RNR-1 is highly homologous to r-NGFI-B/m-Nur77 particularly in the DNA binding (94%) and putative ligand binding (59%) domains. Using a mobility shift assay, we have shown that RNR-1 specifically binds to the NGFI-B DNA half-site and forms a complex very similar in size to the Nur77 complex, suggesting that RNR-1 also may bind as a monomer. Consistent with this finding, the A box region important in mediating half-site binding is 100% conserved between r-NGFI-B/m Nur77. Both RNR-1 and Nur77 strongly transactivate a reporter driven by a consensus r-NGFI-B/Nur77 binding site, and their effect together is additive. As both the RNR-1 and r-NGFI/m-nur77 genes are induced during liver regeneration, it is very possible that RNR-1 acts concomitantly with r-NGFI/m-Nur77 in regulating the expression of delayed-early genes during liver regeneration. PMID- 8473330 TI - An enhancer for transcription of collagen IV genes is activated by F9 cell differentiation. AB - Expression of collagen IV genes is developmentally regulated and cell type specific. To identify transcriptional control elements for the mouse alpha 2(IV) collagen gene, several promoter constructs were transiently transfected into mouse PYS-2 (parietal yolk sac) cells. Within the 5.5-kb (kilobase) upstream and 8.5-kb downstream sequences from the transcription start site, we have identified several regulatory active regions. Here, we report characterization of the most proximal 0.3-kb enhancer found at 4.5-kb upstream of the alpha 2(IV) collagen gene. This enhancer is transcriptionally active in cells that make collagen IV such as PYS-2 cells and differentiated F9 cells, but has little if any activity in cells that do not make collagen IV including NIH 3T3 cells and undifferentiated F9 embryonal carcinoma stem cells. This enhancer, linked to the herpes simplex virus TK gene promoter, confers a cell type-specific and differentiation-induced expression on the TK gene as well. Mutational and 5' and 3' deletion analysis demonstrate that this enhancer activity requires two identical response elements (GAACAAT) present in the 0.3-kb enhancer sequence. In gel shift assay, the GAACAAT element forms a complex that is specific for cells that make collagen IV. PMID- 8473331 TI - Association of heterogeneous nuclear ribonucleoprotein A1 and C proteins with reiterated AUUUA sequences. AB - Post-transcriptional regulatory mechanisms have been shown to play a major role in gene expression in eukaryotic cells. The presence of a reiterated pentamer (AUUUA) in the 3'-untranslated region (UTR) of mRNAs encoding lymphokines, cytokines, transcription factors, and proto-oncogenes has been shown to be associated with rapid turnover and translation attenuation. Cytoplasmic proteins (70, 50, 43, 36, and 25 kDa) capable of specifically binding to RNAs containing these AU-rich sequences were identified in human peripheral blood T lymphocytes. Levels of the 36-kDa protein were markedly increased following transcriptional, but not translational inhibition, a feature recently reported for hnRNP A1, a protein of comparable mass. Antibodies directed against heterogeneous nuclear ribonucleoproteins (hnRNPs) A1 and C immunoprecipitated 36- and 43-kDa proteins that had bound the AUUUA-rich region contained in the 3'-UTR of granulocyte macrophage colony-stimulating factor mRNA. Recombinant hnRNP A1 was shown to preferentially bind to RNAs containing AUUUA sequences in a specific manner, and displayed comparable patterns to the 36-kDa AU-specific binding proteins following partial proteolysis. These data identify for the first time hnRNP A1 and C as cytoplasmic proteins in human lymphocytes that are capable of specifically associating with reiterated AUUUA sequences present in the 3'-UTR of labile mRNAs. As such, they may play a role as trans-acting factors in the modulation of cytoplasmic mRNA turnover and translation, in addition to their previously characterized roles as pre-mRNA binding proteins involved in nuclear mRNA processing. PMID- 8473332 TI - Cloning, expression, and characterization of Cryptococcus neoformans dihydrofolate reductase. AB - The Cryptococcus neoformans dihydrofolate reductase (DHFR) gene has been isolated from cDNA and genomic DNA libraries. The 690-base pair coding sequence codes for a 25,152-Da protein, which is the largest monofunctional DHFR yet reported. The gene contains two introns, and several putative regulatory sequences have been identified. The coding sequence was placed in a pUC-based expression vector, which expresses C. neoformans DHFR in Escherichia coli at a level of about 5% of the total soluble extract. The expressed DHFR was purified to homogeneity by methotrexate-Sepharose affinity chromatography, followed by anion exchange chromatography on Q-Sepharose. On SDS-polyacrylamide gel electrophoresis, the purified enzyme migrates as a single protein with apparent mass of 28 kDa. The molecular weight, as determined by electrospray mass spectral analysis, and the amino-terminal sequence are in accord with what was predicted from the DNA sequence. Steady state kinetic parameters, effects of pH, salts, and inhibition constants of several anti-folates have been determined. PMID- 8473333 TI - A basis for differentiating among the multiple human Mu-glutathione S transferases and molecular cloning of brain GSTM5. AB - Specific cDNA probes and antisera were employed to interpret genetic polymorphisms of human Mu-class glutathione S-transferases and to provide a basis for identifying individual forms in human tissues. A cDNA probe that cross hybridized with various human and rodent Mu-glutathione S-transferase transcripts, hybridized with at least three discrete components by Northern analysis of RNA from human tissue. The smallest (1.3 kb) transcript was identified as the one that encodes GSTM3-3 subunits. A form designated GSTM5, was cloned from a human brain cDNA library and its sequence determined. The open reading frame of GSTM5 shared a high degree of homology with the sequences of other Mu-class glutathione S-transferases, but its 846-nucleotide 3'-noncoding region was unique and considerably larger than that of any of the other Mu forms. Specific synthetic peptide antigens were utilized to distinguish among Mu-class glutathione S-transferases in different tissues of representative individuals. The primary hepatic transcript was that encoding GSTM1-1 with much lesser amounts of GSTM3-3, but livers were devoid of GSTM2-2, and GSTM5-5. Immunoblots confirmed that null-phenotype individuals lacked the GSTM1 gene rather than its GSTM2 homologue that is nearly identical in its exon sequences. The null phenotype therefore was conspicuous in liver, where GSTM1-1 ordinarily was the predominant Mu transcript, but brain and testis contained all four forms. A general strategy was devised to distinguish among and assign primary structures to individual glutathione S-transferases from human tissue. PMID- 8473334 TI - Biosynthesis of human fibrinogen. Subunit interactions and potential intermediates in the assembly. AB - Stable transfected baby hamster kidney (BHK) cells expressing human alpha, beta, and gamma fibrinogen chains together, in various combinations of any two, or individually, were established. Several types of subunit interactions were observed in the intracellular extracts of the transfected BHK cell lines as well as in Hep G2 cells. These included: 1) formation of alpha gamma dimers linked by a disulfide bond(s), 2) formation of beta gamma dimers linked by a disulfide bond(s), 3) formation of alpha beta gamma half-molecules linked by disulfide bonds, and 4) formation of mature fibrinogen, which was also secreted into the cell culture medium. Analysis of the chain composition confirmed the stoichiometry of the alpha gamma, beta gamma, and alpha beta gamma complexes. These data are consistent with the proposal that the alpha gamma and beta gamma dimers as well as the alpha beta gamma half-molecules are intermediates in the assembly and biosynthesis of fibrinogen. In contrast, disulfide-linked alpha beta complexes were not found in transfected BHK cells or in Hep G2 cells, suggesting that the formation of disulfide bonds between these two chains most likely occurs when alpha beta gamma half-molecules are formed from alpha gamma and/or beta gamma complexes and when alpha beta gamma half-molecules dimerize to generate the mature molecule. Dimers, trimers, and larger oligomers of each individual chain linked by disulfide bonds were also identified when each chain was expressed in the absence of the other two chains. Preferential formation of alpha gamma and beta gamma complexes, rather than oligomers of individual chains, suggested that the oligomers were less likely to be intermediates in the assembly of fibrinogen. A model for fibrinogen assembly is presented based on these results. PMID- 8473335 TI - Platelet-derived growth factor stimulates a biphasic mobilization of arachidonic acid in Swiss 3T3 cells. The role of phospholipase A2. AB - Stimulation of quiescent Swiss 3T3 cells with platelet-derived growth factor (PDGF) increased the initial rate of cytosolic phospholipase A2 activity by 95 +/ 6% over extracts from control cells. Cytosolic phospholipase A2 activity increased rapidly following PDGF treatment (near maximum stimulation by 2.5 min) and was dose-dependent (EC50 = 2 ng/ml). Epidermal growth factor, vasopressin, and phorbol 12,13-dibutyrate also increased cytosolic phospholipase A2 activity but did not produce a sustained mobilization of arachidonic acid in these cells. Detailed kinetic analysis of PDGF-induced arachidonic acid mobilization revealed a biphasic release of 3H radioactivity into the extracellular medium. A first, rapid phase, occurred within 15 min which, like the activation of cytosolic phospholipase A2 activity, was independent of de novo RNA and protein synthesis. After 20 min of stimulation, a second phase became evident which accounts for the majority of arachidonic acid mobilized by PDGF. This second phase was abolished in the presence of either cycloheximide or actinomycin D. Both inhibitors blocked the release of arachidonic acid rather than inhibiting cyclooxygenase activity and consequently prostaglandin E2 production. These findings demonstrate a biphasic mobilization of arachidonic acid in Swiss 3T3 cells by PDGF. Cytosolic phospholipase A2 activity could contribute to the rapid first phase but not the second major phase, which is dependent upon de novo protein synthesis. PMID- 8473336 TI - Structural analysis of the myoglobin reconstituted with iron porphine. AB - Sperm whale apomyoglobin was complexed with iron porphine to examine the influence of completely removed heme side chains on the entire molecular structure. Paramagnetic NMR peak from the proximal histidine of the deoxy protein ensured formation of the iron-histidine bond. Porphine pyrrole-proton NMR signals of the cyanmet and deoxy derivatives are unusually sharp single lines manifesting rapid heme rotation about the iron-histidine bond. X-ray crystallographic structure of the cyanmet derivative, determined with a final R factor of 0.21 for 11,808 independent reflections ranging from 7 to 1.8 A, was resolved at 1.8 A resolution. The result confirmed 1:1 coupling between apomyoglobin and iron porphine. The cyano ligand adopts a bent configuration with an Fe-C-N angle of 127 degrees and a Fe-CN distance of 1.89 A. The overall globin structure and side chain conformations are remarkably similar to those of native myoglobin despite intensive disruption of the original heme-globin interactions. The native apoprotein structure unexpectedly conserved even after iron porphine insertion demonstrates that the complex polypeptide fold of holomyoglobin is more inherent in the amino acid sequence than is generally believed. PMID- 8473337 TI - Interference by PR-bound RNA polymerase with PRM function in vitro. Modulation by the bacteriophage lambda cI protein. AB - Activation of the weak PRM promoter by cI protein is an essential process in the establishment of lysogeny. Much evidence has accumulated that cI protein binds cooperatively to the operators OR1 and OR2 and that protein at the OR2 site contacts RNA polymerase to facilitate open complex formation at the PRM promoter. We had shown previously in vitro that RNA polymerase situated at the nearby PR promoter could interfere with open complex formation at PRM and that an additional mechanism of PRM activation in vitro involved cI-mediated RNA polymerase exclusion from PR. Here we further characterize this second indirect mode of activation. We demonstrate the addition of cI and inactivation of the PR promoter activate open complex formation at PRM similarly over the temperature range from 37 to 20 degrees C in which the extent of activation decreases from 8- to 2-fold. We also show that the binding of cI protein to OR1 is sufficient to effect an increase in the rate of synthesis of abortive RNA products at PRM. This result is difficult to explain based on direct cI-RNA polymerase contacts alone but is readily interpreted in terms of our previously proposed model involving the exclusion of an interfering RNA polymerase from binding at PR. PMID- 8473338 TI - Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state. AB - Recently we reported the isolation of cDNAs for a number of genes that are differentially expressed between nonproliferating early (young) and late (senescent) population doubling level (PDL) WI-38 human, fetal lung-derived, fibroblast-like cells. We now demonstrate that one of these isolates, EPC-1 (early PDL cDNA-1), derives from an approximately 1.4-kilobase mRNA species that is expressed at a > or = 100-fold higher level in serum-starved, confluent, young versus similarly treated senescent WI-38 cells. Complete nucleotide sequence analysis of this cDNA confirms its identity with that of a cDNA encoding a secreted, retinal pigmented epithelium differentiation factor as well as similarity of the encoded protein with a number of mammalian serine protease inhibitors. We show that EPC-1 expression is associated with G0 growth arrest in WI-38 cells. The mRNA readily accumulates in density-arrested and/or serum starved young cells but not in log phase, low density young cells. In contrast, EPC-1 transcript abundance and expression of the encoded, secreted protein are both negligible in senescent WI-38 cells under all culture conditions tested. These findings support the hypothesis that senescent WI-38 cells exhibit a state of growth arrest fundamentally distinct from that of quiescent (G0) young cells. PMID- 8473339 TI - CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line. AB - The earliest biochemical event known to be associated with T cell receptor (TCR) engagement is the activation of a protein tyrosine kinase thought to be a member of the src family. Expression of CD45, the major receptor tyrosine phosphatase present on T cells, is required for efficient coupling between the TCR and its signaling machinery. One model to explain the role of CD45 in regulating TCR signaling is that the phosphatase dephosphorylates the regulatory C-terminal tyrosine of lck. In the present report we confirm the finding of a trimolecular complex containing CD45, lck, and a 34-kDa protein (p34) in the Jurkat T cell line. Additionally, we extend this work with the observation that specific in vitro kinase activity associated with CD45 requires the expression of lck in Jurkat-derived clones as does the in vivo phosphorylation of p34. The association between CD45 and lck is shown not to require the expression of or activation of the TCR. Finally, we demonstrate that even in the absence of lck p34 associates with CD45, implying a direct association between this molecule and the phosphatase. These data suggest strongly that lck is the relevant protein tyrosine kinase found in CD45 immunoprecipitates in the Jurkat T cell line and that there is an additional association between CD45 and p34 which does not require the presence of the protein tyrosine kinase. PMID- 8473340 TI - Inhibition of the copper incorporation into ceruloplasmin leads to the deficiency in serum ceruloplasmin activity in Long-Evans cinnamon mutant rat. AB - Although ceruloplasmin is known to be a copper-transporting protein, little is known about the biochemical mechanisms of copper incorporation into ceruloplasmin during the biosynthesis. We have examined various levels of ceruloplasmin biosynthesis in the Long-Evans Cinnamon (LEC) rat, which possesses a mutation causing the deficiency in serum ceruloplasmin activity associated with excess hepatic copper accumulation. Southern and Northern blot analyses revealed that the gene and mRNA encoding ceruloplasmin resided normally in LEC rat liver. Western blot analysis showed a normal level of ceruloplasmin in LEC rat serum. Following metabolic labeling of hepatocytes with 64Cu, no radioactive copper was detected in the ceruloplasmin fraction in LEC rat hepatocytes using Sephadex G-75 column chromatography, indicating that copper incorporation into ceruloplasmin is deficient in the LEC rat. Furthermore, LEC rat hepatocytes incubated with 64Cu also showed a reduction in the efficiency of copper transport from cytosolic to noncytosolic fractions and a reduced copper efflux from the hepatocytes, indicating that LEC rat hepatocytes possess an abnormality in copper metabolism. These results suggest that an abnormality of the copper delivery mechanism causes an inhibition of copper incorporation into the ceruloplasmin molecule in the liver, leading to the deficiency in serum ceruloplasmin activity in the LEC rat. In addition, this abnormality also seems to cause an inhibition of biliary copper excretion. The blocking of these two copper exclusion pathways is thought to lead to excess hepatic copper accumulation in the LEC rat. Thus, the LEC rat should be a good model for studying the biochemical process responsible for copper delivery. PMID- 8473341 TI - Conformational change and membrane association of the PutA protein are coincident with reduction of its FAD cofactor by proline. AB - The PutA protein is both the put repressor and a membrane-bound enzyme with proline and delta 1-pyrroline-5-carboxylate dehydrogenase activities. The conditions required for association of purified PutA protein with membrane vesicles suggested that a redox switching mechanism might determine the proportion of PutA protein functioning as a dehydrogenase (Wood, J. M. (1987) Proc. Natl. Acad. Sci. USA 84, 373-377). The FAD cofactor was released from the PutA protein with 1 M KBr at neutral pH. The apoprotein retained delta 1 pyrroline-5-carboxylate dehydrogenase and DNA binding but not proline dehydrogenase activity. Reconstitution with FAD fully restored proline dehydrogenase activity. Proline at a concentration of 0.11 mM caused half-maximal bleaching of the FAD in PutA. Chymotryptic digestion of the PutA protein in the presence and absence of proline demonstrated that the persistence of a 119-kDa protein fragment was characteristic of the reduced protein. Identical digestion patterns were obtained from the apoprotein in the presence and absence of proline. The quantity of the 119-kDa fragment produced varied with proline concentration, yielding a midpoint of 0.056 mM proline. The fraction of PutA protein associated with membrane vesicles was also a function of proline concentration, yielding a titration midpoint of 0.10 mM proline. Membrane binding was thus coincident with both flavin reduction and a change in protein conformation. PMID- 8473342 TI - Phenotypic analysis of proteinase A mutants. Implications for autoactivation and the maturation pathway of the vacuolar hydrolases of Saccharomyces cerevisiae. AB - We have isolated a number of mutants deficient in activity of the vacuolar hydrolase proteinase A (PrA). The mutations were sequenced and although they all map in the PEP4 gene, which encodes the precursor to PrA, three distinguishable phenotypes have surfaced. The properties of the pep4-7 missense mutant suggested that the activation of the precursor to proteinase A is due to an autocatalytic cleavage. PrA active site mutations were constructed and resulted in accumulation of PrA antigen in the inactive precursor form. Although protease B (PrB), another vacuolar hydrolase, is not required for the production of active PrA, the active form of PrA that accumulates in a strain lacking PrB is larger than that found in a strain containing active PrB. We have purified this larger form of PrA and determined that it bears 7 additional amino acids at its NH2 terminus. It has become apparent from all the studies performed on the maturation pathway of the vacuolar hydrolases that there is a great deal of redundancy built into the system. PMID- 8473343 TI - Structural and functional domains of the Drosophila ncd microtubule motor protein. AB - Nonclaret disjunctional (ncd) is a kinesin-related microtubule motor protein that is required for proper chromosome distribution in Drosophila. Despite its sequence similarity to kinesin heavy chain, ncd translocates with the opposite polarity as kinesin, toward microtubule minus ends. We have expressed different regions of the protein in bacteria and analyzed the proteins for function. Results indicate that ncd consists of three domains: a basic, proline-rich N terminal "tail," a central alpha-helical coiled-coil stalk, and a C-terminal motor domain. The ncd N terminus proteins bundle microtubules in motility assays and show ATP-independent binding to microtubules in solution. Truncated proteins, lacking the tail but containing the predicted motor domain and differing lengths of the stalk, did not support microtubule gliding in in vitro assays but showed microtubule-stimulated MgATPase activity in solution. Addition of a nonspecific N terminus to two of the truncated proteins restored directional gliding and rotation of microtubules in motility assays, demonstrating that these properties map to the predicted mechanochemical domain of ncd. Physical properties of the C terminus proteins indicate that the stalk region is important for dimerization and that the ncd protein probably exists and functions as a dimer. PMID- 8473344 TI - Dissociation of heparin-dependent thrombin and factor Xa inhibitory activities of antithrombin-III by mutations in the reactive site. AB - Antithrombin-III (AT-III) is a heparin-dependent inhibitor of thrombin and Factor Xa, two serine proteases that are crucial for blood coagulation. In order to assess whether it would be possible to target AT-III only towards Factor Xa, we replaced parts of the reactive site, or P region, of AT-III by sequences present in prothrombin, a substrate of Factor Xa in the coagulation cascade. We show that replacement of the P3 to P3' region generates the hypothesized phenotype. In fact, point mutation of the P1' site from Ser (present in AT-III) to Ile (present in prothrombin) is sufficient to dissociate heparin-dependent thrombin and Factor Xa inhibitory activities. Interestingly, a combined mutation at P3 and P3' brings about the same dissociation. We show that besides Ile, other amino acids at P1' can lead to the dissociation in inhibitory activity. Amino acids with small side chains (Gly, Ser, Ala, and Thr) have only a marginal effect on the inhibitory activity against either protease. However, larger residues at the P1' position abolish the heparin-dependent anti-thrombin activity, whereas the heparin dependent anti-Factor Xa activity is not at all or only moderately affected. These results can be rationalized by a comparison of the x-ray structure and a three-dimensional model of the S1' binding pockets of thrombin and Factor Xa, respectively. It appears that the S1' pocket of Factor Xa leaves much more space for the P1' residue of AT-III than the S1' pocket of thrombin. PMID- 8473345 TI - Polarized secretion of thrombospondin is opposite to thyroglobulin in thyroid epithelial cells. AB - In addition to thyroglobulin, primary thyrocytes secrete into the culture medium significant quantities of p500, a protein so named because of its M(r) > or = 500,000. Epithelial monolayers cultured on porous filters serve as a useful model system in which to study protein secretion. From these monolayers, thyroglobulin, the precursor in thyroid hormonogenesis, was released with apical predominance, while p500 was found mostly in the basolateral medium. Thyrocyte exposure to thyrotropin augmented selectively thyroglobulin but not p500 production. By contrast, exposure to cycloheximide actually augmented p500 production, a response observed for immediate-early proto-oncogenes. Using thyrocyte conditioned medium, the p500 protein was purified to homogeneity. Peptide sequencing of tryptic fragments of purified p500 showed identity to thrombospondin. Immunoprecipitation of thrombospondin from media bathing primary thyrocytes and the FRTL5 cell line quantitatively recovered p500, confirming its identity and indicating an epithelial origin. Gel filtration of secreted thrombospondin eluted at a high molecular weight, suggesting complexation with components of the extracellular matrix. Further, immunofluorescence showed cellular codistribution of thrombospondin and thyroglobulin, although thrombospondin exhibited predominantly an extracellular, basolateral deposition. It seems likely that thrombospondin production by thyrocytes plays a role in the growth or development of the thyroid epithelium. PMID- 8473346 TI - Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. AB - Prostaglandin endoperoxide synthase (PHS) catalyzes the committed step in the biosynthesis of prostaglandins and thromboxane. We recently observed dissociation of PHS activity and enzyme mass measured in an immunoassay of endothelial cells exposed to tumor necrosis factor. These data and observations by others suggested that endothelial cells express an alternate PHS. We now report the molecular cloning of human PHS type II from an endothelial cell cDNA library. The protein encoded by this cDNA shares 61% identity with the human PHS I. Southern analysis demonstrated a single copy of PHS II and we found a polymorphism in approximately 5% of the population. PHS II mapped to chromosome 1, in contrast to PHS I, which is on chromosome 9. The PHS II cDNA hybridized strongly to a 4.3-kilobase (kb) message from endothelial cells. Stimulation of the cells with tumor necrosis factor, phorbol 12-myristate 13-acetate, lipopolysaccharide, or interleukin-1 increased mRNA levels for PHS II, and this change correlated well with increased prostacyclin biosynthesis. Cycloheximide induced PHS II mRNA without a corresponding activity increase demonstrating that translation of the 4.3-kb message is required for increased prostacyclin biosynthesis. We conclude that expression of PHS II may have important pathophysiological effects in the vasculature. PMID- 8473347 TI - Fpg protein of Escherichia coli is a zinc finger protein whose cysteine residues have a structural and/or functional role. AB - The Fpg protein of Escherichia coli is a DNA repair enzyme with DNA glycosylase, abasic site nicking, and deoxyribose excising activities. Analysis of the amino acid sequence of this protein suggests that the Fpg protein is a zinc finger protein with a Cys-X2-Cys-X16-Cys-X2-Cys motif. Competition experiments show that the Fpg protein substitutes Cu(II), Cd(II), and Hg(II), metal ions classically associated with substitutions in zinc finger proteins. The Fpg protein activities are inhibited following the reaction with a Cys-specific reagent at low protein:reagent ratios, suggesting that these residues are important for the enzymatic activities. Site-directed mutagenesis was used to produce 6 mutant Fpg proteins with Cys-->Gly mutations. Substitution of the zinc in these proteins by 65Zn(II) indicates that all the proteins bind zinc, but the Zn(II) is not retained as strongly in the zinc finger mutants. The mutations in the Fpg protein outside the zinc finger consensus sequence do not eliminate the Fapy-DNA glycosylase and abasic site nicking. One of the Fpg mutant proteins outside the zinc finger has a reduced capacity to release deoxyribose from abasic sites. Cys- >Gly mutations in the zinc finger consensus sequence reduce all three aforementioned activities substantially. The purified Fpg proteins with Cys-->Gly mutations in the zinc finger consensus sequence do not incise DNA at abasic sites with the same efficiency nor mechanism as the native Fpg protein. The wild type Fpg protein and the Fpg proteins mutated outside the zinc finger sequence bind an oligonucleotide with a unique chemically reduced abasic site in a defined sequence as assayed by retention on nitrocellulose filters, whereas the mutant Fpg proteins within the zinc finger sequence do not bind to the same oligonucleotide. Therefore, the disruption of zinc coordination in the zinc finger of the Fpg protein is associated with decreased binding capacity to DNA as well as decreased enzymatic activities. PMID- 8473348 TI - Purification and characterization of a novel zinc-proteinase from cultures of Aeromonas hydrophila. AB - While searching for an enzyme capable of breaking epsilon-(gamma-Glu)-Lys isopeptide bonds cross-linking protein chains, we purified a metallo-proteinase which mimics the action of an isopeptidase on the gamma-chain dimers of cross linked fibrin. The enzyme is present in the growth medium of the bacterium Aeromonas hydrophila, isolated from the intestinal tract of the leech Hirudo medicinalis. It is a 19-kDa protein which specifically hydrolyzes the Gly-Ala peptide bond within the Gly-Gly-Ala sequence, located near the cross-link site in the gamma-chain dimer of fibrin. Substrate specificity studies with a number of synthetic peptides suggest that the enzyme prefers Gly-Gly or acetyl-Gly in the P2 and P1 positions, respectively (Schecter, I., and Berger, A. (1967) Biochem. Biophys. Res. Commun. 27, 157-162). Nonpolar amino acid residues seem to be favored in the P1' and P2' positions. The enzyme contains one atom of zinc and is inhibited by 1,10-phenanthroline, but not by EDTA. Iodoacetate, leupeptin, diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, pepstatin, and alpha 2-macroglobulin have no effect on enzyme activity. Disulfide reducing reagents, such as dithiothreitol or 2-mercaptoethanol, inactivate the enzyme completely. The partial amino-terminal sequence shows 46% identity with a zinc metallo proteinase from a strain of Lysobacter enzymogenes and 69% identity with the LasA protein from Pseudomonas aeruginosa. PMID- 8473349 TI - Interleukin-6 activates and regulates transcription factors of the interferon regulatory factor family in M1 cells. AB - Activation of (2'-5') A synthetase gene expression in interleukin-6 (IL-6) treated myeloleukemic M1 cells correlates with protein binding to the interferon response sequence enhancer (IRS). A new interferon response sequence complex, F6, is induced by IL-6 independently of interferon and is identified here as comprising the interferon regulatory factor-1 (IRF-1) and IRF-2, by use of specific antibodies in DNA mobility shift assays with probes containing IRF binding sites. IRF-1 and IRF-2 have, respectively, positive and negative transcriptional effects on interferon-beta and interferon-inducible genes. In the IL-6-treated M1or cells, IRF-1 binding is activated early and maximally at 1 h, whereas the onset of IRF-2 binding is delayed. In a cell variant M1res, where (2' 5') A synthetase is no more induced, IRF-2 binding is constitutive, and IRF-1 binding is not seen before or after IL-6 treatment. In sensitive M1or cells, IL-6 rapidly induces IRF-1 mRNA, but in M1res cells, IRF-1 mRNA is constitutively high and not changed by IL-6. IRF-2 mRNA levels are also constitutive and not inducible by IL-6 even in M1or cells. The dissociation between induction of mRNAs and of protein binding observed suggests that the activity of the IRF proteins is regulated by IL-6. Transcripts of a third member of the IRF gene family, ICSBP, encoding a protein known to act as repressor, were found to be strongly down regulated by IL-6. The rapid activation of IRF-1 and the modulation of the other transcription factors of this family may play a role in the early phase of IL-6 action on the M1 cells. PMID- 8473350 TI - Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11 beta), but the salt-sensitive hypertensive rat does not. AB - Molecular cloning of cytochrome P450(11 beta) cDNAs from the adrenal glands of Dahl's salt-sensitive hypertensive (DS) and salt-resistant normotensive (DR) rats was performed using a combined technique of the first strand cDNA synthesis by reverse transcriptase followed by polymerase chain reaction. The cDNA sequence of P450(11 beta)-DS was identical to that of wild type P450(11 beta). In contrast, the clone obtained from the DR rat contained six nucleotide substitutions causing five amino acid alterations (Arg-127-->Cys, Val-351-->Ala, Val-381-->Leu, Ile-384 ->Leu, and Val-443-->Met). When the two cDNAs were expressed in COS-7 cells and steroid conversion rates of the transformed cells were determined, a ratio of 18 hydroxylation to 11 beta-hydroxylation of 11-deoxycorticosterone by P450(11 beta) DS-expressed cells was 0.58, whereas that by P450(11 beta)-DR-expressed cells was 0.23. Plasma levels of 18-hydroxy-11-deoxycorticosterone and corticosterone (the 11 beta-hydroxylation product of 11-deoxycorticosterone) in DS and DR rats well reflected the steroidogenic activities of the two P450s. These results suggest that the characteristic plasma steroid level of the DR rat is caused by the mutations in P450(11 beta) gene and may act to maintain the normotensive blood pressure in this rat strain during sodium loading. PMID- 8473351 TI - Functional divergence of protein kinase C (PKC) family members. PKC gamma differs from PKC alpha and -beta II and nPKC epsilon in its competence to mediate-12-O tetradecanoyl phorbol 13-acetate (TPA)-responsive transcriptional activation through a TPA-response element. AB - We have established an assay system where overexpression of a specific protein kinase C (PKC) type caused by introduction of the respective cDNA results in the enhancement of a cell response: the transcriptional activation of a set of genes in response to PKC activators such as 12-O-tetradecanoylphorbol 13-acetate (TPA). When monitored by the expression of a reporter gene containing the chloramphenicol acetyltransferase gene fused downstream of a synthetic TPA response element (TRE) or a serum response element (SRE), the overexpression of cPKC alpha and -beta II or nPKC epsilon all resulted in the enhancement of transcriptional activation through both TRE and SRE. On the other hand, PKC gamma activates TRE only very weakly, although it activates SRE in a similar manner to the other PKC members examined. The overexpression of cPKC alpha and -beta II or nPKC epsilon, but not cPKC gamma, resulted in the enhanced expression of the endogenous c-jun gene, which contains TRE in the 5'-upstream, promoter region. The gel mobility shift assay showed that the activation of PKC gamma, as well as PKC alpha and -beta II and nPKC epsilon, causes the increase in TRE-binding proteins, suggesting that transcriptional activation through TRE requires an additional step, which is not activated by PKC gamma, such as a qualitative change in TRE-binding or in TRE-associating proteins. This finding provides not only a rationale to explain the presence of multiple PKC family members, but also permits the dissection of the complex cellular signaling cascade involving PKC family members. PMID- 8473352 TI - Isolation and characterization of rat CYP11B genes involved in late steps of mineralo- and glucocorticoid syntheses. AB - We isolated and characterized four forms of rat CYP11B genes, which were tentatively named CYP11B1, -B2, -B3, and -B4. Genomic Southern analyses indicated that the members of the rat CYP11B gene subfamily were confined to these four genes; among them, CYP11B1 and -B2 encoded steroid 11 beta-hydroxylase and aldosterone synthase, respectively, while CYP11B3 was a gene highly homologous to CYP11B1 without a known expression product. By being devoid of a region spanning two exons conserved in the other three, CYP11B4 was presumably a pseudogene. In the nucleotide sequences, CYP11B1, -B3, and -B4 showed 95-96 and 93-100% identities in the coding and 0.5-kilobase 5'-flanking regions, respectively. However, the homology between the nucleotide sequences of one of the three and CYP11B2 was rather low, about 90 and 50% in the coding and 0.5-kilobase 5' flanking regions, respectively. As a whole, CYP11B2 rather than CYP11B1, -B3, or B4 was more homologous to CYP11B genes of other animals such as cow and human. In transient transfection experiments using mouse adrenocortical Y1 cells and chloramphenicol acetyltransferase gene constructs, the 0.5-kilobase 5'-flanking region of CYP11B1 had a 4- and 10-fold higher promoter activity than the corresponding regions of CYP11B2 and -B3, respectively. The possible presence of a suppressive element(s) was noted in the upstream of the 0.5-kilobase region of CYP11B1. Although a variant of cAMP-responsive element, which was present in rat CYP11B2 and all known CYP11B genes of other animals, was modified in rat CYP11B1 and -B3 genes, dibutyryl cAMP stimulated all the promoter activities of the 5' flanking regions of the rat genes by 3-fold. PMID- 8473353 TI - Human eosinophil cytotoxicity-enhancing factor. Eosinophil-stimulating and dithiol reductase activities of biosynthetic (recombinant) species with COOH terminal deletions. AB - U937 cells produce eosinophil cytotoxicity-enhancing factor (ECEF) polypeptides of 14 and 10 kDa that have identical NH2-terminal amino acid sequences. The 10 kDa form has greater eosinophil-stimulating activity (half-maximal at > 20-fold lower concentration). We considered the hypothesis that there is a precursor product relationship between the 14- and 10-kDa species. Recombinant 14-kDa 104 amino acid ECEF (rECEF-104) had a slight stimulatory effect on eosinophil cytotoxic function at concentrations of 160 nM and above. In contrast, two species, rECEF-80 and rECEF-84, representing cleavage products of approximately 10 kDa had substantial statistically significant cytotoxicity-enhancing activity at concentrations as low as 10 pM. This evidence demonstrates the potential to generate the high-activity ECEF species by proteolytic cleavage of the 104-amino acid species. Another feature of this cytokine is the sequence from amino acids 31 to 34, which constitutes the conserved and active site of the enzyme thioredoxin. When tested for dithiol reductase enzymatic activity, rECEF-104 was active in a dose- and time-dependent manner, whereas the truncated forms of the molecule had no dithiol reductase activity. Thus the eosinophil-stimulating functions of the molecule do not correlate with its enzymatic activity. The evidence shows that the enzymatic activity is not essential for the initial interaction of ECEF with the eosinophil, and it suggests that the ECEF molecule functions by means of two discrete mechanisms. PMID- 8473354 TI - Transcriptional activation of the inducible nuclear receptor gene nur77 by nerve growth factor and membrane depolarization in PC12 cells. AB - nur77 is an immediate-early gene inducible by nerve growth factor or membrane depolarization in the rat pheochromocytoma cell line PC12 and by serum growth factors in fibroblasts. The nur77-encoded protein is a member of the steroid/thyroid hormone receptor superfamily and can act as a potent transcription activator. The induction of nur77 in PC12 cells is rapid and transient, with kinetics similar to those of the c-fos protooncogene. Induction does not require de novo protein synthesis. Whereas transcriptional activation of c-fos by nerve growth factor in PC12 cells requires a 20-base pair serum response element in its promoter, there is no such sequence in the nur77 promoter. To understand the mechanism for the activation of nur77, we have analyzed the inducibility of a series of transfected nur77 minigenes using an S1 nuclease protection assay. We identified the sequence 22-86 nucleotides upstream of the transcription start site as necessary and sufficient for nur77 induction by nerve growth factor and membrane depolarization in PC12 cells. Sequences farther upstream enhance the induction. Analysis of base substitution mutations allowed us to identify three sequence elements within this region that are essential for induction. These sequence elements include two copies of an AP1-like element and a GC-rich sequence. Unlike transcriptional activation of c-fos, the sequence requirements for the activation of nur77 by nerve growth factor and membrane depolarization cannot be readily separated. Taken together, our data suggest that activation of nur77 and c-fos by nerve growth factor occurs through different mechanisms in PC12 cells. PMID- 8473355 TI - Memories of a childhood pharmacy. PMID- 8473356 TI - Dry and photo-aged skin: manifestations and management. AB - A review is presented on the causes and management of dry and photo-aged skin. The causative factors discussed range from adverse weather conditions to serious dermatological disease. The potential use of moisturizers in certain clinical cutaneous disorders. The main types of skin moisturizers and anti-ageing substances currently available are reviewed with particular emphasis on the rationale behind their development. PMID- 8473357 TI - Vitamin therapy in cystic fibrosis--a review and rationale. AB - Vitamin supplements are routinely prescribed in cystic fibrosis, but published recommendations vary widely and there is little consistency in clinical practice. A review of the literature confirms that, while supplementation of the water soluble vitamins (including B12 and folate) is unnecessary in uncomplicated cystic fibrosis, deficiency of the fat-soluble vitamins can lead to clinical problems. Supplements of these vitamins should be ensured for all patients with cystic fibrosis, while sparing them the unnecessary inconvenience of taking other vitamin supplements except where these are specifically indicated. PMID- 8473358 TI - Effect of oral activated charcoal on propranolol pharmacokinetics following intravenous administration to rabbits. AB - The pharmacokinetics of propranolol following intravenous administration (1 mg/kg), with and without treatment with oral activated charcoal, was investigated in rabbits. In charcoal-treated rabbits a significant reduction in propranolol serum concentrations was observed compared to control animals. Charcoal treatment significantly reduced the half-life of elimination (16.6%) and the mean residence time (19%) of propranolol. A 17% increase in the systemic clearance and a 14% decrease in AUC were also noted. Charcoal administration did not significantly alter the volume of distribution (Vc' V(area) and Vss) or the apparent distribution half-life. A two-compartment model adequately described propranolol in control and treated rabbits. The results indicate that administration of oral activated charcoal enhances the systemic elimination of propranolol. This is presumably mediated by interruption of the enterohepatic circulation of propranolol by activated charcoal. PMID- 8473359 TI - Drug-induced thrombocytosis. AB - Thrombocytosis is generally defined as platelet counts greater than 400,000/mm3. Thrombocytosis can be either primary or secondary. Adrenalin was one of the first drugs noticed to cause platelet elevations, probably due to demargination of platelets in the pulmonary vasculature. Vinca alkaloids have the most convincing data to show that they can induce thrombocytosis through their thrombocyte stimulating properties. Miconazole has been implicated in causing thrombocytosis and has a documented case validated by drug rechallenge. Iron, predictably, can cause a transient thrombocytosis. The beta-lactam antibiotic data are very difficult to interpret due to the possibility of an acute-phase reaction in an infected patient being the cause of the thrombocytosis. PMID- 8473360 TI - Paracetamol poisoning and the kidney. AB - Nephrotoxicity is less common than hepatotoxicity in paracetamol overdose but renal tubular damage and acute renal failure occur even in the absence of hepatotoxicity. It is possible that antidotal therapy with agents such as N acetylcysteine may not prevent renal toxicity and, indeed, on the basis of animal work, may actually potentiate tubular damage. Careful clinical attention should be paid to renal function in patients poisoned with paracetamol. PMID- 8473361 TI - Estimation of population pharmacokinetics for carbamazepine in Malaysian patients using the OPT computer program. AB - We used OPT to estimate individual and population pharmacokinetics for carbamazepine (CBZ) in Malaysian epileptic patients attending our Neurology Clinic. We noted that plasma CBZ concentrations and clearances correlated poorly with daily doses and body weights respectively but we found the values for clearance, volumes of distribution, elimination rate constants and half lives to be in good agreement with earlier reports. We conclude that OPT is a simple yet useful program to derive individual and population pharmacokinetic parameters for CBZ for use in dosage adjustments. We also conclude that although the Malaysian population do not differ substantially in handling CBZ, available data for the pharmacokinetic parameters must be used cautiously in applying it to the therapeutic drug monitoring for CBZ in our patients. PMID- 8473362 TI - Treatment of nephrotic syndrome associated with idiopathic rapidly progressive glomerulonephritis and cyclosporin A. AB - Recent reports suggest that cyclosporin A is beneficial in inducing remission of idiopathic nephrotic syndrome. Nephrotic syndrome is seen in 10-30% of patients with rapidly progressive glomerulonephritis. We report a case of a 69-year-old man with nephrotic syndrome, associated with idiopathic rapidly progressive glomerulonephritis, who was treated initially with corticosteroid and cyclophosphamide. Three months later he developed thrombophlebitis and leucopenia and cyclophosphamide was suspended. Relapse of nephrotic syndrome associated with rapidly progressive glomerulonephritis developed and therapy with cyclosporin A was used with a good response. PMID- 8473363 TI - Digoxin pharmacokinetics in patients with high serum digoxin concentrations. AB - Digitalis intoxication is a frequent iatrogenic effect in patients on treatment with digoxin. In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml. A control group of patients was used as a reference whose population pharmacokinetic parameters obtained by a maximum likelihood method were: Vd = 542.92 +/- 274.53 (litre); Cl = 8.73 +/- 1.55 (litre/h) (mean +/- SD). Statistically significant differences (P < 0.001) were found between the mean Cl values in both groups of patients. The difference between the dose-level ratios established in both populations studied also proved to be significant (P < 0.001). Calculation of the optimum dose for each patient showed that the doses recommended in intoxicated patients should be three times lower than those used in the control population. A good correlation was found between the concentrations observed 24 h after administration and the mean concentrations observed at steady state predicted for both population groups. Multiple regression analysis showed that the variables with the greatest predictive value for clearance in intoxicated patients were age and renal function. The modifications observed in the pharmacokinetic behaviour and in the response to digoxin in this type of patient suggest systematic monitoring using pharmacokinetic and clinical criteria jointly. PMID- 8473364 TI - Stability of lorazepam diluted in bacteriostatic water for injection at two temperatures. AB - Lorazepam is commonly used to produce sedation in infants. As errors may occur with the measurement of small volumes of concentrated drugs, we studied the stability of lorazepam diluted from 4 mg/ml to 1 mg/ml in bacteriostatic water for injection at two temperatures. The diluted lorazepam was stored in 10 glass vials (five at 22 degrees C and five at 4 degrees C). Samples were collected at 0, 7, 14, 28, 42, 56, 70 and 91 days after storage at each temperature. Lorazepam was measured in duplicate from each of five vials (n = 10) at each temperature by a specific and stability-indicating high-performance liquid chromatographic (HPLC) method. After 7 days' storage, the mean lorazepam concentration was 88% of the original concentration at 22 degrees C, and 90% of the original concentration at 4 degrees C. After 2 weeks of storage, the mean lorazepam concentration was 42% of the original concentration at 22 degrees C, and 1.5% of the original concentration at 4 degrees C. Crystals appeared after 4 weeks of storage at 22 degrees C and after 2 weeks of storage at 4 degrees C. At 3 months the mean lorazepam concentration was 6.1% and 7.5% of the original concentration at 22 degrees C and 4 degrees C, respectively. Thus, lorazepam diluted in bacteriostatic water for injection and stored in glass vials is stable for less than 7 days at 22 degrees C and for 7 days at 4 degrees C. PMID- 8473365 TI - Strategies for non-insulin-dependent diabetes mellitus. PMID- 8473366 TI - Managing prostate cancer. Part II: Disseminated disease. AB - Each year in the United States, approximately 100,000 men are found to have prostate cancer. Of these, about half show evidence of bony metastases at the time of presentation. Each year, too, some 30,000 American men die of prostate cancer. Conceptually, the treatment of metastatic prostate cancer has changed little in the 50 years since Charles B. Huggins and Clarence V. Hodges discovered the hormone-dependent nature of prostate cancer cells. Still, as the years have passed, several therapeutic options have become available. For the most advanced cases, treatment centers on relief of urinary obstruction and amelioration of the pain of bony metastases, along with vigilance for the potentially disastrous sequelae of acute neurologic change due to spinal fractures. In Part I of this article, which appeared in the April 15 issue of Hospital Practice, we discussed the assessment and management of localized carcinoma of the prostate. In this part, the focus shifts to disseminated disease (Figure 1). We again present two cases representing distinctly different points on the spectrum of disease and discuss how management would proceed in each case. This strategy affords an opportunity to review the various available treatment options, with their advantages and drawbacks. PMID- 8473367 TI - Diagnosis and treatment of celiac sprue. AB - Celiac sprue, also termed celiac disease or gluten-sensitive enteropathy, is a chronic disease in which malabsorption of nutrients is caused by a characteristic, but nonspecific, lesion of the small-intestinal mucosa. The lesion is produced, through unclear mechanisms, by protein constituents of some cereal grains. Exclusion of wheat gluten and rye, barley, and oat prolamins from the diet results in a prompt improvement in absorption, along with reversion, toward normal, of the associated small-intestinal lesion. The spectrum of manifestations of celiac sprue is remarkably broad, but the severity of disease generally correlates with the length of small intestine that is damaged. When most or all of the small-intestinal mucosa is involved, symptoms are severe and malabsorption is generalized. In such patients, a diagnosis of celiac sprue is usually considered. When, on the other hand, the mucosal lesion is limited to the duodenum and proximal jejunum, overt gastrointestinal symptoms and steatorrhea may be absent. In those patients, clinical manifestations, if present at all, may reflect malabsorption of only one or two substances, notably iron and folate, that normally are absorbed somewhat selectively by the proximal intestine. Arriving at the correct diagnosis in such cases may be quite challenging. PMID- 8473368 TI - Electroconvulsive therapy in the elderly. PMID- 8473369 TI - The need for office-based precepting. PMID- 8473370 TI - Five cases in search of a diagnostician. PMID- 8473371 TI - Magnesium: deficiencies and therapeutic uses. AB - Hypomagnesemia, which may be difficult to diagnose, can complicate diabetes mellitus or a variety of cardiovascular diseases. In some patients, an infused multielectrolyte preparation is often the best solution. PMID- 8473372 TI - Colorimetric detection for PCR amplified HIV-1 DNA using magnetic beads. AB - A rapid and nonradioactive detection method for polymerase chain reaction (PCR) amplified HIV-1 DNA was developed using a colorimetric detection system. Hybridization between biotin-labeled amplified targets and digoxigenin-capture probes occurs in solution followed by efficient and rapid capture onto streptavidin-magnetic beads. The presence of the digoxigenin-capture probe hybridized with biotin-labeled targets is then detected by antidigoxigenin alkaline phosphatase conjugates using a colorimetric substrate. This approach is highly sensitive and can detect less than 10 HIV targets prior to PCR in approximately 50 min. PMID- 8473373 TI - Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies. AB - Idiopathic Addison's disease is a chronic organ-specific autoimmune disorder with a long subclinical period characterized only by the presence of adrenal autoantibodies (AA) with or without adrenal function failure. The aim of this longitudinal study was to evaluate the behavior of AA using, an indirect fluorescence method, and adrenal function in 20 AA-positive and 50 AA-negative patients screened by an investigation of a large population of organ-specific autoimmune disease patients without clinical Addison's disease. As controls, 100 normal age-matched subjects were tested only once. In the 20 AA-positive and 50 negative patients, AA and adrenal functional tests were evaluated every 4 months for 5 yr. The AA-positive patients were grouped into 5 adrenal functional stages, specifically: stage 0, normal adrenal function; stage 1, high PRA and low (or normal) aldosterone levels alone; stage 2, along with impaired cortisol response to ACTH, stage 3, along with increased ACTH levels; and stage 4, clinically overt Addison's disease. On the basis of the behavior of AA, the 20 positive patients were grouped as follows: group A, 11 patients with AA titer of 1:8 or higher at the first observation and persistently AA positive in subsequent observations, with titers ranging from 1:8 to 1:64; group B, 6 patients with initial AA titers of 1:8 or lower and AA disappearance in subsequent observations; and group C, 3 patients with AA titer of 1:32 or higher, undergoing corticosteroid therapy after the start of the study and showing AA disappearance in subsequent observations. With respect to adrenal function in group A, 2 patients initially in stage 1 and 1 patient initially in stage 2 did not progress to the upper stages, whereas 5 patients initially in stage 0 and 3 initially in stage 1 progressed subsequently to the upper stages, in 2 cases reaching overt clinical Addison's disease (stage 4). On the other hand, all of the patients of group B showed both a spontaneous disappearance of AA and recovery of adrenal function during the study span. Also, the 3 patients of group C showed disappearance of AA after corticosteroid therapy with recovery of adrenal function. None of the 50 patients who were initially AA negative became AA positive subsequently or showed impairment of adrenal function. We reached the following conclusions. 1) AA, even if present initially in some subjects without clinical Addison's disease, can subsequently disappear. 2) Restoration of adrenal function after disappearance of AA indicates that a spontaneous remission of subclinical adrenocortical failure can occur.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8473374 TI - Concanavalin A affinity chromatography of human serum gonadotropins: evidence for changes of carbohydrate structure in different clinical conditions. AB - We have studied the carbohydrate of circulating human gonadotropins (FSH and LH) in different clinical conditions using Concanavalin A (Con A) affinity chromatography. This technique permits separation of molecules differing in the extent of carbohydrate branching. The proportion of molecules that does not bind to Con A was greater in circulating FSH than in LH, reflecting a higher content of multiantennary and/or bisected biantennary complex carbohydrate structures in serum FSH. No significant difference in gonadotropin binding pattern to Con A was found between normal controls and patients with chronic uremia or gonadotropin secreting pituitary adenomas. On the contrary, sera from postmenopausal women and fetuses contained a greater proportion of FSH and LH that bound to Con A, indicating a shift from multiantennary and/or bisecting structures to hybrid and/or high mannose forms, i.e. to the secretion of less mature forms. International Reference Preparations, derived from pituitary extracts, were more retained on Con A than circulating hormones, suggesting that carbohydrate chains of the intrapituitary hormone stock are less mature than those present in the circulation. Less mature forms were also found in FSH, but not in LH, from normal controls after GnRH injection. Finally, a higher proportion of unbound forms, i.e. complex carbohydrate chains, was found in healthy subjects presenting with an immunologically anomalous variant of LH. In conclusion, the current data show that the hormonal status of the individual may differently affect carbohydrate branching of gonadotropins. Alteration in glycosylation is likely to be involved in masking at least one epitope specific for intact LH dimer, thus indicating that it may modulate the tertiary structure of glycoprotein hormones. PMID- 8473375 TI - Atrial natriuretic hormone: a paracrine or endocrine role within the human placenta? AB - There is evidence to suggest that the human placenta may synthesize atrial natriuretic hormone (ANH). To test this hypothesis we examined specimens of normal term placenta obtained at elective caesarean section for evidence of either storage or synthesis of this peptide. No immunocytochemical or ultrastructural evidence of ANH storage was found. RNA extracted from cultured cytotrophoblast cells, the chorionic or decidual plates, or from placental villi contained no ANH-encoding messenger RNA by Northern blot analysis. Polymerase chain reaction amplification of these RNA extracts using primers directed to the midportion of the ANH gene failed to demonstrate any evidence of ANH-encoding RNA. We conclude that ANH is neither stored nor synthesized within the normal term placenta, and thus a purely endocrine role for this peptide within the fetoplacental compartment is proposed. PMID- 8473376 TI - Oral gossypol in the treatment of metastatic adrenal cancer. AB - Medical treatment of metastatic adrenal cancer is largely unsuccessful and has considerable toxicity. We previously demonstrated the activity of the plant toxin gossypol against human adrenal cancers in nude mice. We therefore examined the efficacy and toxicity of oral gossypol as a treatment for adrenal cancer in humans. Twenty-one patients with metastatic adrenal cancer received oral gossypol at doses of 30-70 mg/day. Patients were monitored for side effects of gossypol, changes in hormone secretion, and tumor response. Eighteen patients completed at least 6 weeks of gossypol treatment. Three of these patients, whose tumors were refractory to other chemotherapeutic agents, had partial tumor responses (> or = 50% decrease in tumor volume) that lasted from several months to over 1 yr. One patient had a minor response followed by resection of her remaining disease, 1 patient had stable disease, and 13 patients had disease progression. Three patients died of their disease without receiving sufficient gossypol to achieve detectable drug levels, and were eliminated from the final analysis. The side effects of gossypol were generally well tolerated; the only serious side effect was abdominal ileus that resolved when the drug was temporarily withheld and restarted at a lower dose. We conclude that oral gossypol can be used relatively safely on an outpatient basis for the treatment of metastatic adrenal cancer. The response rate is similar to the other agents currently available for adrenal cancer, and responses were seen in patients who had failed other chemotherapeutic regimens. This study provides the first indication that gossypol may have activity against cancer in humans, suggesting the need for further investigation of gossypol as an antitumor agent. PMID- 8473377 TI - Thyrotropin-producing microadenoma associated with pituitary resistance to thyroid hormone. AB - A 21-yr-old female with hyperthyroidism is described. Though her serum-free T3 was 17.8 pmol/L and free T4 was 60.2 pmol/L, TSH was as high as 10.7 mU/L. TRH stimulated an increase in TSH from 10.7-91.7 mU/L. T3 administration in gradually increasing doses of 100, 200, and 400 mg/day resulted in gradual reduction in serum TSH. Cranial computed tomography and magnetic resonance imaging revealed a microadenoma of the pituitary gland. Histology of the surgical specimen showed a TSH-producing adenoma with TSH cell cluster islets and decreased numbers of TSH cells in the nonneoplastic pituitary. Cultured cells from the adenoma secreted TSH spontaneously and in response to TRH. This TRH-stimulated TSH secretion was suppressed by T3 in a dose-dependent manner. One year postoperatively, neither residual tumor nor recurrence were seen by computed tomography and magnetic resonance imaging. However TSH, as well as free T3 or T4, was still high and overresponsive to TRH. PMID- 8473378 TI - The effect of light on core body temperature is mediated by melatonin in women. AB - Acute exposure to bright light at night reduces the nocturnal decline of core body temperature (cBT) and inhibits melatonin secretion in men. Since inhibition of melatonin secretion by beta-adrenergic blockade reduces the nocturnal decline of cBT by 40% in women, experiments were performed to investigate whether the thermoregulatory effect of light is mediated by modifications of melatonin secretion in cycling women. Results show that the elevation of cBT induced by nocturnal exposure to bright light (3000 lux) can be reversed completely by circumventing the decline of serum melatonin levels with concurrent oral administration of melatonin. Our finding establishes melatonin as the mediator of the effect of light on cBT in women and provides a rationale for the use of orally administered melatonin as an aid in the reentrainment of the cBT rhythm in desynchronized conditions. PMID- 8473379 TI - Growth hormone induces insulin resistance in Laron dwarf cells via lactogenic receptors. AB - GH is the hormone primarily responsible for regulating body size within the genetic program. While GH has pleiotropic actions on cellular growth and metabolism, most of its effects are believed to be mediated by a single GH receptor. This receptor is not functional in tissues from patients with Laron dwarfism. We used human T-cell leukemia virus-immortalized T-lymphoblast cell lines from Laron dwarfs and normal individuals to examine the mechanism of GH induced insulin resistance at the cellular level. GH (5-500 micrograms/L) caused a profound decrease in the sensitivity of normal T-lymphoblasts in response to all insulin concentrations (P < 0.0001 vs. insulin alone); pretreatment with GH and GH receptor antibody significantly improved sensitivity to all concentrations of insulin (P = NS vs. insulin alone). Preincubation with GH and PRL receptor antibody was associated with partial improvement in insulin sensitivity (P = 0.004 vs. insulin alone). Thus, in normal T-cell lines, the major pathway of GH induced insulin resistance appears to be directed by the GH receptor, with a smaller effect mediated through the PRL receptor. While T-cell lines from Laron dwarfs do not respond to GH in clonal proliferation assays, GH (50 and 100 micrograms/L) caused profound insulin resistance in these cells (P = 0.008 and P < 0.0001, respectively, vs. insulin alone). GH receptor antibody did not abrogate this effect at any insulin concentration (P = NS vs. insulin alone), but there was partial restoration of insulin sensitivity when GH and PRL receptor antibody were coincubated (P = 0.0069 vs. insulin alone). Thus, in Laron T-cell lines, PRL and perhaps other lactogenic receptors appear to mediate GH-induced insulin resistance. The kinetics of GH-induced insulin resistance in Laron T-cells were also distinct from the pattern seen in normal T-cells, and unlike in normal cells, GH had no effect on insulin-like growth factor-I-induced clonal expansion of Laron T-cell lines (P = NS vs. insulin-like growth factor-I alone). These results provide evidence for an alternative pathway of GH action revealed in cells lacking classical growth responses to GH. PMID- 8473380 TI - Alterations in luteinizing hormone secretory activity in women with insulin dependent diabetes mellitus and secondary amenorrhea. AB - To investigate hypothalamic and/or pituitary abnormalities in women with poorly controlled insulin-dependent diabetes mellitus (IDDM) and secondary amenorrhea, we measured serum LH every 10 min for 24 h and for 2 additional h after the administration of exogenous GnRH in 8 women with IDDM and amenorrhea and compared these to data from 15 eumenorrheic nondiabetic women. LH pulses were characterized by the pulse detection algorithm Cluster, and secretory episodes were evaluated using the multiple parameter deconvolution procedure Deconv. Cluster analysis revealed fewer LH pulses per 24 h (14.3 +/- 1.2 vs. 19.9 +/- 0.6; P < 0.001; mean +/- SEM), a greater peak width (63 +/- 4.9 vs. 44 +/- 2.2 min; P < 0.01), and greater peak area (136 +/- 17 vs. 89 +/- 13 IU/L.min; P < 0.01) in the diabetic women. Analysis with Deconv revealed fewer LH secretory episodes per 24 h in the diabetic women (14.4 +/- 0.9 vs. 20.4 +/- 0.5; P < 0.001) and no statistical difference in LH half-lives. The IDDM women responded to a 10-micrograms GnRH bolus with LH pulses of larger total (51 +/- 15.9 vs. 15 +/- 1.4 IU/L; P < 0.01) and incremental (29 +/- 7.6 vs. 9 +/- 1.2; P < 0.001) amplitude. In summary, we observed that amenorrheic diabetic women have fewer LH pulses/secretory episodes than normal women. However, they respond well to exogenous GnRH, suggesting that compromise of the GnRH pulse generator, rather than pituitary dysfunction, is responsible for their menstrual dysfunction. PMID- 8473381 TI - Spontaneous growth hormone release in term infants: changes during the first four days of life. AB - Healthy term infants have higher umbilical cord GH levels compared to older infants and children. In the sheep, GH concentrations rapidly fall within an hour of birth; the physiology of GH release after parturition in the human term infant is less well known. The purpose of this study was to investigate spontaneous 12-h GH release in male and female term infants of varying postnatal ages. We studied 14 infants (7 males and 7 females). Subjects were divided into those studied earlier following delivery (28.2 +/- 3.4 h of age, mean +/- SE) and into those studied at a later time (74.8 +/- 3.5 h, P < 0.0005). The age at study was defined as the age (hours) when blood sampling began. There were eight infants studied at an early age (four males and four females) and six studied at a later age (three males and three females). Subjects were comparable with respect to gestational age, birth weight, and length; all were biochemically euthyroid. One infant was large for gestational age although his head circumference was in the normal range. Blood (0.1 mL) was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double-antibody RIA using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor I (IGF-I) was measured following separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences in GH characteristics were found between male and female subgroups in the early or late study groups. In subsequent analysis, the data for the males and females are combined. The GH pulse frequency per 12 h was greater in the earlier studied group, 5.1 +/- 0.9 (mean +/- SE) vs. 2.5 +/- 0.7 in the later group (P < 0.05). The maximal pulse amplitude was 47.1 +/- 7.9 micrograms/L in the early and 27.1 +/- 4.1 in the later studied group (P < 0.06). The incremental pulse amplitude was 26.4 +/- 3.4 micrograms/L in the early and 12.8 +/- 2.7 in the later group (P = 0.01). The pulse width was greater in the later studied group (202.8 +/- 71.1 min vs. 84.1 +/- 21.6, P < 0.06).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8473382 TI - Corticotropin-releasing hormone in baboon pregnancy. AB - During human pregnancy, plasma CRH immunoreactivity (CRH-IR) rises progressively, peaking during labor and falling after delivery. Among animal species, only higher primates have elevated CRH-IR during pregnancy. This study examines whether changes in plasma CRH-IR in the baboon (Papio hamadryas) are similar to those in the human. CRH-IR was determined by RIA in 16 baboons at different stages of gestation (44 samples) and in 3 males. Assays were performed on Vycor extracts of plasma and CRH-IR diluted in parallel to synthetic human (h) CRH-41 standard. Reverse phase high pressure liquid chromatography and size-exclusion chromatography with Sephadex G-50 showed that baboon CRH-IR eluted in a position similar to that of hCRH-41. Regression analysis revealed a cubic association between plasma CRH-IR and gestational age, with peak concentrations occurring at 60 days gestation (term = 182 days). Although greatly elevated concentrations persisted throughout pregnancy, concentrations in the first half (1-91 days) were significantly higher (mean +/- SEM, 1.9 +/- 0.3 nM/L; n = 27) than in the second half (92-182 days; 1.0 +/- 0.2 nM/L; n = 11; P < 0.003 by t test). CRH-IR fell to low levels by day 1 postpartum. The concentration of total cortisol in nonpregnant animals was 1370.9 +/- 134.9 nM/L (n = 5), which was similar to pregnancy levels (1346.3 +/- 356.1 nM/L; n = 28); there was no gestational age related pattern evident. Plasma corticosteroid-binding globulin was estimated by RIA, and plasma free cortisol was calculated to be 73 +/- 14 nM/L in pregnant animals and showed no gestational age-related changes. The mean progesterone concentration in the pregnant baboon was 12.5 +/- 2.2 nM/L (7-169 days; n = 27). There was no significant change in progesterone levels during the period of gestation studied; however, they were higher than nonpregnant levels. Baboon and human plasma (0.1 mL each) were incubated with [125I]Tyr-hCRH in Tris-HCl buffer (pH 7.5) and chromatographed with Sephadex G-75, using the same buffer. The radioactivity of fractions was determined, and no CRH-binding protein was identified in baboon plasma. This study indicates that gestational changes in CRH IR in the baboon are different from those observed in humans. There is a dissociation between maternal plasma CRH and cortisol. The apparent lack of bioactivity of baboon plasma CRH is not due to a circulating binding protein, which is absent in this species. PMID- 8473383 TI - Ingestion of androgenic-anabolic steroids induces mild thyroidal impairment in male body builders. AB - Self-administration of very high doses of androgenic anabolic steroids is common use in power athletes because of their favorable effect on performance. Since androgenic steroids decrease serum T4-binding globulin (TBG) concentrations dramatically, we were interested in the effects of this procedure on thyroid function: we performed TRH tests (200 micrograms Relefact, i.v.), with blood withdrawal before and for 180 min after injection, for determination, using RIA kits, of serum concentrations of total and free T4, total T3, TSH, and TBG in 13 young (20-29 yr old) male body builders with clinically normal thyroid glands, who were all in the same state of training. Five of these athletes admitted taking androgenic anabolic steroids at an average total dose of 1.2 g/week for at least 6 weeks before the tests. TBG, total T4, and total T3 were significantly (P < 0.001) decreased, whereas basal TSH and free T4 were not significantly different from the values of the other 8 without androgenic steroids. The maximum TSH increase after TRH administration (mean +/- SE, 16 -/+ 6 vs. 9 -/+ 4 mU/L; P < 0.05) was relatively increased, whereas the T3 response to TRH (0.61 -/+ 0.10 vs. 1.13 -/+ 0.13 nmol/L; P < 0.05) was relatively decreased in the group receiving androgens. The 5 patients taking androgens had significantly greater weight (114 vs. 90 kg; P < 0.01) and higher total cholesterol levels (6.3 -/+ 1.3 vs. 3.8 -/+ 0.3 mmol/L; P < 0.05) together with very low high density lipoprotein cholesterol levels (0.20 -/+ 0.03 vs. 1.03 -/+ 0.10; P < 0.001) than the controls. PRL levels were normal and similar in both groups. We conclude from our results that high dose androgenic anabolic steroid administration leads to a relative impairment (within the normal range) of thyroid function. Whether this is due to a direct thyroid hormone release (or synthesis?)-blocking effect of these steroids needs further investigation. PMID- 8473384 TI - Islet amyloid polypeptide-like immunoreactivity in human tissue and endocrine tumors. AB - We have detected islet amyloid polypeptide (IAPP)-like immunoreactivity (-LI) in human pancreas and in a range of endocrine tumors, including oat cell carcinoma of the lung and pancreatic tumours producing insulin, gastrin, glucagon, and vasoactive intestinal peptide. Gel permeation chromatography of the IAPP-LI revealed that, except in the carcinoid, more than 80% coeluted with synthetic human IAPP. The remaining immunoreactivity consisted of variable amounts of larger and smaller molecular forms. The concentration of IAPP-LI in the circulation of patients with diagnosed pancreatic endocrine tumors was not significantly elevated above normal fasting levels. IAPP is, therefore, produced by a range of endocrine tumors and may relate to the deposition of endocrine amyloid. PMID- 8473385 TI - Human plasma free activin and inhibin levels during the menstrual cycle. AB - The role of inhibin in gonadal function and reproduction has been confirmed by the measurement of plasma inhibin levels, but there has been no clinical data available on activin because of the lack of a good assay method. We measured plasma free activin levels during the normal menstrual cycle using a newly developed competitive protein binding assay with follistatin as the binding protein. Plasma inhibin levels were measured simultaneously using an alpha subunit N-terminal fragment RIA with recombinant inhibin as the reference standard. Four normal women, aged 23-29 years, were investigated by obtaining plasma at 3-day intervals. Plasma inhibin levels showed some variation during the follicular phase, but a parallel rise in inhibin and progesterone was observed during the luteal phase. These findings confirmed those of previous studies. In contrast, plasma free activin levels did not show any substantial changes during the menstrual cycle. This study suggests that activin has no endocrine role in modulating the pituitary-gonadal axis during the normal menstrual cycle, while changes of inhibin reflect cyclic gonadal function and indicate an endocrine role for this protein in modulating gonadal activity. PMID- 8473386 TI - Clinical review 44: Medullary thyroid carcinoma: recent progress. PMID- 8473387 TI - Peking Union Medical College Hospital, a palace of endocrine treasures. PMID- 8473388 TI - A new dimension on the induced release of growth hormone in obese subjects. PMID- 8473389 TI - Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. AB - GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state. PMID- 8473390 TI - X-chromosome-linked Kallmann's syndrome: pathology at the molecular level. PMID- 8473391 TI - Xp22.3 deletions in isolated familial Kallmann's syndrome. AB - Several familial cases of Kallmann's syndrome (KS) have been reported, among which the X-chromosome-linked mode of inheritance is the most frequent. The gene responsible for the X-linked KS has been localized to the terminal part of the X chromosome short arm (Xp22.3 region), immediately proximal to the steroid sulfatase gene responsible for X-linked ichthyosis. Large deletions of this region have been previously shown in patients affected with both X-linked ichthyosis and KS. We report here the search for Xp22.3 deletions in 20 unrelated males affected with isolated X-linked KS. Only 2 deletions were found using Southern blot analysis, indicating that large deletions are uncommon in patients affected with KS alone. Both deletions were shown to include the entire KAL gene responsible for X-linked KS. The patients carrying these deletions exhibit additional clinical anomalies, which are discussed: unilateral renal aplasia, unilateral absence of vas deferens, mirror movements, and sensory neural hearing loss. PMID- 8473392 TI - Assay of brain natriuretic peptide (BNP) in human plasma: evidence for high molecular weight BNP as a major plasma component in heart failure. AB - A RIA for human brain natriuretic peptide (BNP) was developed. Both BNP and atrial natriuretic peptide (ANP) were extracted from human plasma with Vycor glass powder (71% recovery for BNP). The assay had a minimum detection limit of 0.45 fmol/tube and an IC50 of 9 fmol/tube. The within-assay coefficients of variation were 11.4% at 4 pmol/L and 3.2% at 22 pmol/L, and the between-assay coefficient of variation was 11% at 24 pmol/L. There was no significant loss of immunoreactive (IR)-BNP in plasma samples stored at -80 C for 4 weeks. Low rates of labeled BNP and IR-BNP degradation occurred in EDTA plasma incubated at 37 C. The mean venous plasma IR-BNP (6.3 +/- 0.3 pmol/L) in normal subjects (n = 48) was significantly lower than plasma ANP (8.4 +/- 0.6 pmol/L). In contrast to ANP, IR-BNP did not increase when normotensive or hypertensive subjects changed from erect to supine posture. Markedly elevated levels were found in patients with congestive heart failure (mean IR-BNP, 87 +/- 11 pmol/L; ANP, 87 +/- 12 pmol/L; n = 35), recent myocardial infarction (mean IR-BNP, 60 +/- 9 pmol/L; ANP, 33 +/- 6 pmol/L; n = 7), and chronic renal failure. High pressure liquid chromatography of plasma extracts from heart failure subjects revealed both high (mol wt, 10,000) and low (mol wt, 4,000) mol wt IR-BNP. High mol wt BNP was the major component (mean ratio, 1.9:1) and was linearly correlated with low mol wt BNP (r = 0.99). HPLC of plasma extracts from three normal subjects receiving constant infusions of human BNP (2 pmol/kg.min) showed a single major peak eluting in the position of hBNP-32, with no evidence of high mol wt material. These results show that whereas marked elevations in BNP occur in circulatory disorders, a major (> 50%) and consistent contribution to immunoreactivity is due to precursor forms. Further, compared to ANP, there is no IR-BNP response to supine posture in normal and hypertensive subjects. PMID- 8473393 TI - Effects of calcitriol and phosphorus therapy on the growth of patients with X linked hypophosphatemia. AB - Patients with X-linked hypophosphatemic rickets exhibit clinically evident derangements that include bowed legs and short stature. Although contemporary treatment may result in healing of the rachitic/osteomalacic disorder and straightening of the lower extremities, therapy often does not stimulate growth. Whether such persistent short stature is related to the variable physical manifestations of the disease, the baseline biochemistries, and/or the biochemical response to treatment remains unknown. Therefore, we studied 12 children with X-linked hypophosphatemia to determine if their growth response to calcitriol/phosphorus therapy was dependent upon anthropomorphic characteristics and/or the pre- and posttreatment biochemistries. We observed that growth responsive and resistant youths exhibited similar serum calcium, phosphorus, and creatinine levels at presentation and during therapy. In addition, sexual development was indistinguishable in both groups and growth kinetics appeared independent of physical deformity. In contrast, growth resistant youths presented at less than the 5th percentile whereas growth responsive children were at the 15th percentile or greater. Thus, our data indicate that growth response to calcitriol/phosphate therapy is not a consequence of the biochemical response to therapy or physical deformities. Rather, the criterion that best predicts the growth response is the height percentile at the inception of therapy. PMID- 8473394 TI - Effects of different plasma glucose concentrations on lipolytic and ketogenic responsiveness to epinephrine in type I (insulin-dependent) diabetic subjects. AB - The effects of two different plasma glucose concentrations (5 and 10 mmol/L) on lipolysis and ketogenesis during baseline and in response to epinephrine infusion were evaluated in insulin-dependent diabetic patients. Each insulin-dependent diabetic subject was studied during euglycemia, hyperglycemia with hypoinsulinemia, and hyperglycemia with hyperinsulinemia. Total ketone body (TKB) concentrations were significantly higher in hyperglycemic-hypoinsulinemic diabetics than in hyperglycemic-hyperinsulinemic and normoglycemic diabetics. Hyperglycemic-hyperinsulinemics had higher TKB concentrations than euglycemic diabetics. During epinephrine infusion, the ketone body rate of appearance and concentration significantly increased in all groups. Plasma FFA concentrations were significantly higher in hyperglycemic-hypoinsulinemic diabetics than in the other groups. During epinephrine infusion, the plasma FFA rate of appearance and concentration significantly increased in all groups. The apparent fraction of FFA converted to ketones was increased by epinephrine in all groups, except in hyperglycemic-hyperinsulinemic diabetics. In conclusion, this study demonstrates that although insulin alone decreases FFA and TKB concentrations, it does not affect the fraction of FFA converted to ketones. If hyperinsulinemia is superimposed on hyperglycemia, there is both a reduction of ketogenesis capacity, compared to hyperglycemia alone, and a decrease in the apparent fraction of FFA converted to ketone bodies. PMID- 8473395 TI - The relationship between luteinizing hormone and estradiol secretion in female precocious puberty: evaluation by sensitive gonadotropin assays and the leuprolide stimulation test. AB - We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP. PMID- 8473396 TI - Familial short stature with very high levels of growth hormone binding protein. AB - We report a familial syndrome of short stature associated with partial GH resistance and very high levels of GH binding protein (GHBP). In three individuals of the same family, presenting with growth failure, high circulating GH levels, both basal and stimulated, were found. Insulin-like growth factor-1 plasma levels were either normal or in the low normal range. GH binding activity was extremely elevated in the plasma of the three subjects, with very high maximum binding capacity (30- to 110-fold higher than that of normal adult plasma) and normal binding affinity (5-7.4 x 10(8) M-1). The cause and the exact consequences of the very high level of plasma GHBP, resulting in a low proportion of free circulating GH, remain to be clarified. The short stature and the partial GH resistance are probably related to high GHBP levels. PMID- 8473397 TI - Turner syndrome adolescents receiving growth hormone are not osteopenic. AB - Deficits in bone mineral have been widely reported in Turner syndrome. The bone mineral status of 19 adolescents with Turner syndrome (16 receiving GH therapy) was evaluated by dual photon absorptiometry of the lumbar spine and whole body and compared with a normal female control group (n = 45) with the same mean age (14.3 yr). The conventional measurements of bone mass, bone mineral content (BMC = g), and bone mineral density (BMD = g/cm2), as well as bone mineral apparent density (BMAD = g/cm3), an expression of bone mineral adjusted for bone volume, were determined for both sites. Although mean BMC was decreased in Turner females, mean BMD and BMAD in the two groups were not significantly different. Analyzed in relation to chronologic age, bone age, height, and pubertal status, mean BMD and BMAD values in Turner subjects were equal to or greater than that of controls. BMD and BMAD were elevated in the Turner group vs. controls matched for height. In subjects with bone age less than or equal to 12.5 yr, mean spinal BMAD was unexpectedly greater in Turner patients compared with controls (0.148 +/- 0.011 vs. 0.134 +/- 0.013, P = 0.009). When data were analyzed by pubertal status, mean spinal BMD and BMAD in subjects with Tanner breast stages 1-2 were higher in the Turner group than in the controls (BMAD 0.146 +/- 0.011 vs. 0.132 +/- 0.015, P = 0.015). No differences were seen in mid- to late pubertal females. Bone mineral properties were additionally reassessed after a mean interval of 1.3 yr in 10 of the subjects with Turner syndrome. Percentage increases in mean follow-up spinal BMD and BMAD were greater in 5 subjects begun on estrogen replacement than in 5 untreated patients. We conclude that: 1) bone mineral values in adolescents with Turner syndrome on GH therapy are not abnormal, 2) lumbar bone mineral is greater in younger Turner adolescents matched with controls for bone age or pubertal status, a difference which could relate to GH therapy, and 3) estrogen therapy may augment bone mineral accretion in Turner syndrome, but early estrogen replacement cannot be justified on the basis of bone mineral status. PMID- 8473398 TI - The calciotropic hormone response to changes in serum calcium during exercise in female long distance runners. AB - The purpose of this study was to evaluate the effects of 45 min of submaximal running on calciotropic hormone levels in female long distance runners. Fourteen long distance runners and six sedentary controls (less than three exercise sessions per week) had bone mineral density (BMD) of the lumbar spine (L2-L4), femoral neck, and tibia measured by dual photon absorptiometry. All of the sedentary controls and eight runners (NormR) had BMD values within the normal range for women of their age. The remaining six runners had BMD L2-L4 measures greater than 1 SD below normal values and were classified as the low bone density group (LowR). Subjects were tested for their calciotropic hormone response to submaximal running using both an oral calcium load (dairy product), to induce a significant elevation in serum calcium, and no calcium load. In both exercise tests, serum calcium rose in NormR and LowR, with a greater increase induced by the oral calcium load. In NormR, the increase in serum calcium resulted in decreased PTH levels, with small increases in calcitonin levels. In contrast, LowR showed significant (P < 0.05) increases in PTH levels, with concurrent decreases in calcitonin levels. The changes in calciotropic hormone levels were shown to be significantly associated with BMD. Our results suggest that in well trained female runners with low spinal bone density, long distance running may aggravate this condition through the effect of exercise-related elevations of PTH on bone turnover. Alterations in the homeostatic control mechanisms for calcium during exercise should also be considered in the clinical assessment of female runners with spinal osteopenia. PMID- 8473399 TI - The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism. AB - 18-Hydroxycortisol and 18-oxocortisol have been isolated from the urine of patients with aldosterone producing adrenocortical adenomas, but not from those with idiopathic hyperaldosteronism associated with bilateral adrenal hyperplasia. These C-18 oxygenated cortisols are biosynthesized by the substitution of cortisol for the normal substrate, corticosterone, in the terminal oxidase system required for the biosynthesis of 18-hydroxycorticosterone and aldosterone. To make use of this biochemical difference between the two groups in the preoperative diagnosis of primary aldosteronism, we have developed and utilized a specific primary standard analytical method, stable isotope dilution mass fragmentography, for quantifying 18-hydroxycortisol and the tetrahydro metabolite of 18-oxocortisol in 24-h urine samples. The normal range by this technique of 4.6 +/- 1.8 micrograms/day tetrahydro 18-oxocortisol and 43 +/- 23 micrograms/day 18-hydroxycortisol in urine was lower and narrower than previous estimates using other methods. Excretion of the 18-oxocortisol metabolite ranged from 2-12 micrograms/day in bilateral hyperplasia and 17-1203 micrograms/day in typical adenomas. 18-Hydroxycortisol excretion similarly separated bilateral hyperplasia (23-59 micrograms/day) from typical adenomas (60-2750 micrograms/day). The cortisol C-18 oxidation pathway describes a unique steroidogenic mechanism in the aldosteronoma not present in idiopathic aldosteronism due to bilateral adrenal hyperplasia and as such provides a basis for the biochemical classification of primary aldosteronism and the differentiation of these two groups. This unique biochemistry was also observed in unilateral hyperplasia but not in the renin dependent aldosteronoma. PMID- 8473400 TI - More basic forms of both human follicle-stimulating hormone and luteinizing hormone in serum at midcycle compared with the follicular or luteal phase. AB - The purpose of this study was to compare the heterogeneity and median charge of FSH and LH in serum at different phases of the normal human menstrual cycle. Serum specimens were obtained during the follicular phase [9.0 +/- 1.9 (+/- SD) days before the midcycle], at the midcycle LH peak, and during the luteal phase (9.75 +/- 1.6 days after the midcycle) in 16 women with normal menstrual cycles. The 48 serum specimens were subjected to electrophoresis in 0.17% agarose suspension in 0.075 M veronal buffer at pH 8.6, using a column suitable for measuring the median charge of the isoforms of FSH and LH, expressed as median electrophoretic mobility. Four sera were also analyzed by use of a larger column, giving a high resolution. The FSH and LH activities were measured with a time resolved sandwich fluoroimmunoassay. The number of isoforms of both FSH and LH in each serum specimen analyzed by electrophoresis with high resolution was between 20-30. The median charge of the isoforms of FSH was less negative (P < 0.001) at the midcycle than in the follicular or luteal phase in all 16 women. The same was found for LH in 14 of 15 women. The median charge of FSH or LH in the follicular phase was not significantly different from that in the luteal phase of the cycle. We conclude that at least 20-30 isoforms of both FSH and LH circulate in blood during the menstrual cycle. More basic isoforms of both hormones appear in serum at midcycle than in the follicular or luteal phase. The difference is most likely due to a selective secretion from the pituitary of more basic forms of FSH and LH at midcycle. PMID- 8473401 TI - Diltiazem stimulates parathyroid hormone secretion in vivo whereas felodipine does not. AB - The impact of two calcium channel blockers of different structure, diltiazem and felodipine, on PTH secretion was studied under hyper- and hypocalcemic conditions. Six healthy volunteers were investigated before and after treatment with felodipine, then after treatment with diltiazem. Under each of these three conditions, they received first a calcium infusion (0.109 mmol/kg over 130 min). Blood was drawn every 5-10 min for measurements of Ca2+ and intact PTH concentrations, and urine was collected over the infusion periods for measurements of calcium and creatinine. Basal levels of Ca2+ and intact PTH concentrations were similar under the three conditions. During calcium infusion, Ca2+ increased linearly from 1.27 to 1.51 mmol/L during the control period. Based on the whole response curve, Ca2+/time, this rise was less marked (P < 0.002) during each of the calcium channel blocker periods than under control conditions, although the three values of urinary calcium excretion were similar. In addition, PTH secretion was less suppressed on diltiazem than on felodipine therapy or during the control period (P < 0.04). During EDTA infusion, Ca2+ decreased in a linear way from 1.27 to 1.07 mmol/L during the control period. Based on the whole response curve, Ca2+/time, this decrease was more marked during felodipine than during diltiazem treatment or in the control period (P < 0.001). Although Ca2+ concentrations did not differ between the control and diltiazem periods, PTH levels were 1.3-fold higher (P < 0.0001) during diltiazem, but similar in the control and felodipine periods. These data demonstrate that diltiazem, but not felodipine, stimulates PTH secretion in vivo in man, with a maximal effect observed under hypocalcemic conditions. PMID- 8473402 TI - Differential effects of glucose stimulation upon rapid pulses and ultradian oscillations of insulin secretion. AB - To determine the effect of glucose stimulation on the rapid 8- to 15-min pulses and the ultradian 80- to 170-min oscillations of insulin secretion, peripheral concentrations of glucose, insulin, and C-peptide were measured at 2-min intervals over 2 h (i.e. rapid experiments), at 15-min intervals over 8-20 h (i.e. ultradian experiments) in 17 normal subjects during saline infusion, or during constant glucose infusion at a rate of 3 mg/(kg.min) (i.e. low dose) or 6 mg/(kg.min) (i.e. high dose). In the ultradian experiments, insulin secretory rates (ISR) were calculated by deconvolution of the plasma C-peptide concentrations. Significant oscillations with 125- to 166-min periods were detected in all glucose and ISR profiles. The numbers of ISR oscillations per 24 h were similar during saline infusion and low and high dose glucose infusion. In contrast, the amplitude of the ISR peaks increased progressively from 14 +/- 1 pmol/min during saline infusion to 50 +/- 7 pmol/min and further to 97 +/- 9 pmol/min during low and high dose glucose infusions, respectively. When expressed as percent increment, the amplitude of the ISR oscillations increased significantly from 31 +/- 5% during saline infusion to 41 +/- 4% during low dose glucose infusion and 44 +/- 3% during high dose glucose infusion (P < 0.05). In all profiles obtained from the 2-min sampling experiments, rapid pulses of glucose, insulin, and C-peptide were apparent. The number of insulin pulses during saline and glucose infusions corresponded to a mean periodicity of 10 min. The amplitude of these rapid insulin pulses increased from 17.3 +/- 2.9 to 39.8 +/- 11.8 pmol/L (P < 0.01) in response to glucose. In contrast to the ultradian oscillations, the relative amplitude of the rapid insulin pulses decreased significantly from 28.8 +/- 3.4% during saline infusion to 13.6 +/- 1.6% during high dose glucose infusion (P < 0.01). Our findings demonstrate that the pancreatic response to glucose stimulation is different for the rapid pulses and the ultradian oscillations. When the rate of glucose stimulation is increased, the absolute amplitude of both the rapid pulses and the ultradian oscillations increases. However, when expressed as percent increment, the amplitude of the rapid pulses decreases during glucose stimulation, whereas the amplitude of the ultradian oscillations increases. These findings suggest that the two oscillatory modes have a different origin and physiological significance. PMID- 8473403 TI - Effect of premature birth and survival on hepatic thyroxine 5'-monodeiodinase activity in baboons. AB - Plasma thyroid hormones and hepatic 5'-monodeiodinase type I (5'-MDI) activity were measured in a primate model of premature birth and survival. When prematurely delivered at 140 days (term gestation is 184 days), infant baboons developed hyaline membrane disease, had no surge in T3 and T4, temporarily developed hypothyroxinemia, and had extremely low T3 concentrations during the first 40 h of life. After 4 days, both plasma T4 and T3 levels progressively increased, but were still considerably lower at 16 days compared to those in normal term infants. Hepatic 5'-MDI activity was measured in the presence of dithiothreitol in fetal, premature, and infant baboons. Fetal baboons at 140 and 161 days gestation had 80% less 5'-MDI activity than term infants, but at 178-180 days gestation, near term, fetal hepatic 5'-MDI activity increased to levels similar to those in young adults. Interruption of in utero development by premature birth resulted in no change in hepatic 5'-MDI activity after 24 h, but within 6 days after delivery, hepatic 5'-MDI had significantly increased to levels observed in fetal baboons near term. Kinetic analysis revealed that fetal and premature 5'-MDI had different maximum velocities and similar apparent Km values. There was no significant difference in hepatic total, protein, or nonprotein sulfhydryl groups between 1- and 10-day-old premature (140 days gestation) baboons. These results suggest that premature birth does not limit the postnatal maturation of hepatic 5'-MDI activity. PMID- 8473404 TI - Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells. AB - The presence and biochemical characteristics of human brain natriuretic peptide (hBNP) in the amniotic fluid at various gestational ages were investigated. The hBNP-like immunoreactivity (hBNP-LI) levels in amniotic fluid, determined by RIA, were 118.7 +/- 57.6 pmol/L (mean +/- SEM; n = 5) and 107.7 +/- 8.7 pmol/L (n = 9) in the first and second trimesters of pregnancy, respectively; it was significantly decreased to 28.4 +/- 5.1 pmol/L (n = 9) in the third trimester. However, human atrial natriuretic peptide-like immunoreactivity (hANP-LI) was not detected (< 0.3 pmol/L) in any of these samples. Northern blot analysis demonstrated hBNP mRNA in human amnion tissue. Moreover, cultured amnion cells secreted a significant amount of hBNP-LI (100-200 fmol/10(6) cells/day), but not hANP-LI, into the culture medium. The synthesis of hBNP in cultured amnion cells was further confirmed using the polymerase chain reaction. High performance gel permeation chromatography of hBNP-LI extracted from human amniotic fluid and the culture medium of amnion cells revealed that the predominant molecular form of hBNP-LI in both samples was the hBNP precursor, with an approximate mol wt of 12 kilodaltons. These findings indicate that hBNP is present in the human amniotic fluid, and that amnion cells synthesize hBNP and secrete it into the amniotic cavity. PMID- 8473405 TI - Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near physiological insulinotropic hormone and glucose concentrations. AB - Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1-(7-36) amide (GLP-1) are glucose-dependent insulinotropic gut hormones that may explain the greater insulin secretory response with oral compared to i.v. glucose (incretin effect). To study their individual and combined contributions, in eight healthy volunteers, on separate occasions, synthetic human GIP (1 pmol/kg.min) and/or GLP 1 (0.3 pmol/kg.min) or placebo were infused i.v. (-30 to 120 min), while at 0 min, a glucose infusion "isoglycemic" to the profile after an oral glucose load of 50 g/400 mL was started. After the administration of 50 g oral glucose, immunoreactive GIP rose several-fold to 337 +/- 43 pmol/L, while there was only a transient (10-30 min) and moderate increment in immunoreactive GLP-1 (from basal, 25-30, to 41 +/- 4 pmol/L). Isoglycemic i.v. glucose infusions led to smaller B cell responses (estimated incretin effect, 41 +/- 5%). With single infusions of GIP or GLP-1 (circulating concentrations, 464 +/- 73 and 54 +/- 3 pmol/L, respectively), B-cell responses were significantly augmented compared to i.v. glucose alone and were no longer significantly different from those after oral glucose. The combination of GIP and GLP-1 led to B-cell responses that were significantly higher than those with either hormone alone (additive mode of cooperation). Plasma GIP concentrations were similar after endogenous secretion (oral glucose) and i.v. infusion, while exogenously administered GLP-1 led to plasma levels that were maintained at an elevated level for a longer period during exogenous infusion than after stimulation by oral glucose. When, in seven volunteers, a lower dose (0.15 pmol/kg.min) of GLP-1 was infused during isoglycemic glucose infusion experiments only for the duration of elevated plasma levels in the oral glucose challenges (0-30 min), a significant, but transient, increment in insulin and C-peptide concentrations was observed, which was equivalent to 26 +/- 10% of the estimated incretin effect. Therefore, in conclusion, circulating GIP seems to make a major contribution to the incretin effect after oral glucose, and GLP-1 appears to mediate a smaller proportion. GIP and GLP-1 can interact in an additive manner in normal man. PMID- 8473406 TI - Origin and significance of plasma androsterone glucuronide levels: a parameter of adrenal androgen secretion and hepatic 5 alpha-reductase activity. AB - To evaluate the reliability of plasma androsterone glucuronide (ADTG) as a parameter of androgenicity at the target tissue level, we studied the origin of ADTG in women, by measuring the plasma conversion rate of different possible precursors as well as by measuring ADTG levels in ovariectomized women and women with Addison's disease. In women, ADTG levels reflect essentially adrenal androgen secretion, dehydroepiandrosterone sulfate (DHEAS) being the major precursor, accounting for 70%-80% of ADTG levels. As estimated from the ADTG/DHEAS ratio in hirsute women (increased peripheral 5 alpha-reductase) and hyperthyroid women (increased hepatic 5 alpha-reductase), it appears that hepatic 5 alpha-reductase is a major determinant of the conversion of precursors to plasma ADTG. In men, plasma testosterone and DHEAS appear to contribute to a comparable extent to plasma ADTG levels, as suggested by data obtained in orchidectomized men and men with Addison's disease. In accordance with the role of DHEAS as a precursor, plasma levels of ADTG decrease significantly with age in both men and women. Our data do not support the concept that plasma ADTG levels reflect primarily peripheral androgen formation. PMID- 8473407 TI - Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate. AB - Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/ 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children. PMID- 8473408 TI - Subnormal androgen and elevated progesterone levels in women treated for congenital virilizing 21-hydroxylase deficiency. AB - Clinical, anthropometric, and endocrine data were examined in 22 corticosteroid treated, prenatally virilized women with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and in 22 matched healthy controls. In view of the androgen excess, limited growth, and subfertility associated with CAH, the investigation focused on androgenic/anabolic status and circulating progesterone levels. CAH patients were shorter and had a significantly higher body mass index than the controls. One pregnancy was reported in the CAH group compared to 15 in the controls. Five of the CAH patients were judged as undersubstituted based on greatly elevated circulating levels of 17 alpha-hydroxyprogesterone. These five patients had elevated serum levels of progesterone (P) and testosterone (T) and elevated ratios between T and sex hormone-binding globulin, but subnormal levels of dehydroepiandrosterone (DHA) and its sulfate. The remaining 17 well substituted patients had elevated follicular phase levels of P, but subnormal levels of all androgens (4-androstene-3,17-dione, T, DHA, and DHA sulfate) and subnormal T/sex hormone-binding globulin ratios. Contrary to the apprehension that normally guides the treatment of CAH, well substituted patients may be considered hypoandrogenic rather than hyperandrogenic. The elevated levels of P may have a minipill-like effect, which may be one of the causes of the differences in fertility between salt-wasting and simple virilizing CAH. PMID- 8473409 TI - Growth hormone (GH) secretion from human lymphocytes is up-regulated by GH, but not affected by insulin-like growth factor-I. AB - Regulation of GH secretion from phytohemagglutinin (PHA)-stimulated lymphocytes was investigated in six normal subjects. Peripheral blood mononuclear cells were incubated with PHA (10 micrograms/mL) in the presence of various amounts of recombinant human GH (0-100 ng/L) and/or recombinant human insulin-like growth factor-I (0-1000 micrograms/L), and the secreted GH was measured by a highly sensitive enzyme immunoassay. PHA-stimulated lymphocytes secreted immunoreactive GH in all subjects (13.6 +/- 2.4 ng/L). Exogenous GH up-regulated the GH secretion in a dose-dependent manner, while IGF-I did not affect either basal GH secretion or the up-regulation by exogenous GH. These findings suggest a difference in the regulation of GH secretion between endocrine and immune systems. PMID- 8473410 TI - Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins. AB - To delineate the activity of the GnRH pulse generator during pubertal transition, 40 healthy girls 7-18 yr of age were studied. Ten were prepubertal (PP), 7 were in early puberty (EP), and 23 were in late puberty (LP, all postmenarcheal). Serum concentrations of LH and FSH were measured with immunofluorometric assays, which have a sensitivity about 100-fold that of RIA, in samples taken at 10-min intervals for 24 h during basal conditions, during Nal-Glu antagonist suppression, and in response to GnRH stimulation (10 micrograms). Serum levels of androstenedione, testosterone, and estradiol were measured with RIA. A pulsatile pattern of LH and FSH secretion was found in girls of all ages. PP girls had irregular LH pulses with low amplitudes during the daytime, but increased amplitude LH and FSH pulses were evident within 1 h after sleep-onset. Older PP girls had more regular and higher amplitude pulses throughout sleep than younger PP girls. The sleep-related LH and FSH pulses in PP girls were abolished with Nal Glu GnRH antagonist treatment, reflecting endogenous GnRH pulse activities. The PP group had the most pronounced amplification of LH secretion with sleep yielding a sleep-wake ratio of 4, which decreased to 2 in the EP group and to 1 in the LP group. The emergence of regular daytime LH pulses along with a further amplification of pulsatile activity during sleep was closely related to the onset of breast development. By the age of 16 yr, an LH secretory pattern characteristic of adult women in the early follicular phase, i.e. a decrease in LH concentration during sleep, was established. Mean 24-h LH concentrations increased 40-fold from PP to LP consequent to a 9-fold increase in pulse amplitude and a 4-fold increase in pulse number (both P < 0.0001). Mean FSH concentrations (24 h), which were 20-fold higher than corresponding LH concentrations in the PP group, increased only 3-fold from the PP to the LP group. FSH pulse secretion appears to be predominantly GnRH dependent in PP girls in contrast to girls after ovarian activation, as indicated by the increased FSH responses to both GnRH antagonist suppression and GnRH stimulation in the PP as compared to the EP and LP groups. We conclude that the GnRH pulse generator is functionally active in prepubertal girls with selective expression of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a greater increase in LH pulse amplitude than frequency.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8473411 TI - Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: a pharmacokinetic study. AB - Recombinant human GH (hGH) combined with a permeation enhancer for the nasal mucosa, sodium tauro-24,25-dihydrofusidate (STDHF), was administered intranasally (in) in six patients with classical GH deficiency. Three different doses were tested (0.2, 0.4, and 0.8 IU/kg BW). The concentration of STDHF was 1% in all doses. As a comparison, all patients received a sc injection of hGH (0.1 IU/kg BW). Blood samples were obtained at frequent intervals for up to 8 h (in doses) or 24 h (sc dose) and analyzed for the plasma concentration of hGH. All three i.n. doses gave a rapid increase in hGH with peak maxima (Cmax) at 20-30 min, and a decline to baseline within 2-3 h. In contrast, the sc dose resulted in a Cmax 2 3 h after the injection, followed by a plateau phase for 2-3 h. The baseline was reached 12-14 h after administration. The uptake [area under the curve (AUC)] was considerably lower for all three in doses, i.e. 1.6-3% of the AUC obtained with the sc dose. However, the Cmax varied between 5.7 +/- 1.4% (0.8 IU/kg BW) and 15.8 +/- 2.1% (0.4 IU/kg BW) of the maximal peak with the sc dose. Of the in doses, 0.4 IU/kg BW resulted in the highest AUC and Cmax. A self-rating protocol was also used to estimate nasal sensations for up to 2 h after dosing. All sensations (itching, burning, sneezing, and running of the nose) were transient and tolerable. This study demonstrates that hGH can be administered intranasally in combination with STDHF. The in dosing results in a plasma peak of hGH very similar to the physiological endogenous peak. No side-effects were noted, other than a transient nasal irritation. Therefore, the nasal route for hGH administration offers a more physiological and more convenient alternative to injections for the treatment of GH deficiency. PMID- 8473412 TI - Mitogenic action, regulation, and localization of insulin-like growth factors in the human fetal adrenal gland. AB - Polypeptide growth factors may play an important role in the regulation of human fetal adrenal cortical growth by mediating the tropic actions of ACTH. The abundance of mRNA encoding insulin-like growth factor-II (IGF-II) is high in the human fetal adrenal gland and is stimulated by ACTH in cultured fetal adrenal cortical cells. Therefore, we studied the mitogenic action, regulation, and localization of IGF-II and a closely related peptide, IGF-I, in primary cultures of human fetal adrenal cortical cells and whole human fetal adrenal glands. Recombinant human IGF-I and IGF-II stimulated proliferation of fetal adrenal cortical cells in a dose-dependent fashion (1-1000 ng/mL; 0.133-133 nM). At 1000 ng/mL (133 nM), both peptides increased cell number 1.8- to 2-fold. Combinations of IGF-I or -II (100 ng/mL; 13.3 nM) with basic fibroblast growth factor (bFGF; 0.1 ng/mL; 6 pM) or epidermal growth factor (EGF; 1.0 ng/mL; 0.17 nM) had a greater effect on proliferation than bFGF, EGF, or either of the IGFs alone, suggesting an additive interaction. IGF-II mRNA was detected in cultured adrenal cortical cells by in situ hybridization analysis, and its abundance was stimulated by ACTH. In contrast, IGF-I mRNA was not detected in cultured fetal zone cells and was not regulated by ACTH. In whole human fetal adrenal glands, IGF-II mRNA was detected in the definitive and fetal zones and in the capsule, whereas IGF-I mRNA was detected only in the capsule and not in the two cortical zones. Using Northern blot analysis, we found that mRNA encoding IGF-II was present in high abundance in fetal adrenal glands (16-22 weeks) and barely detectable in adult adrenals, whereas mRNA encoding IGF-I was present in very low abundance in the fetal adrenal, but was high in adult human adrenals. As IGF-II expression is high in the human fetal adrenal cortex and is regulated by ACTH, we propose that it is the dominant of the two IGFs regulating human fetal adrenal growth. The cooperative mitogenic effect of IGF-II with bFGF and EGF and the regulation of its expression by ACTH support the hypothesis that IGF-II may act as a mediator, in concert with bFGF and possibly EGF, of the tropic action of ACTH in regulating the rapid growth of the human fetal adrenal cortex during midgestation. PMID- 8473413 TI - Androstanediol glucuronide production in human liver, prostate, and skin. Evidence for the importance of the liver in 5 alpha-reduced androgen metabolism. AB - Androstanediol glucuronide (Adiol G) has been reported to be a marker of peripheral androgen metabolism and action. It consists of two isomers, Adiol 3-G and Adiol 17-G. Adiol G is formed from unconjugated precursors by the enzyme glucuronyl transferase. To determine the likely source of Adiol G formation in man, we developed a glucuronyl transferase assay and measured the activity of this enzyme in human liver, abdominal and scalp skin, and prostate. In human liver, glucuronyl transferase activity was linear with respect to time (up to 120 min) and tissue concentration (up to 1 mg/ml). Apparent Michaelis-Menten constant Km (micromolar) and maximum velocity (Vmax) (picomoles per mg/30 min) were 5.6 and 140 for dihydrotestosterone, 8.9 and 1300 for androstanediol, and 3.1 and 46 for androsterone, respectively. Conversion of androstanediol to Adiol G (/0.5 mg tissue.30 min) was 5.8-13.2%. Over 80% of the Adiol G formed in human liver was Adiol 17-G, similar to what has been previously found in human serum. Glucuronyl transferase activity was present at low levels in human prostate (conversion of androstanediol to Adiol G was 0.04-4.6%/50 mg tissue.120 min). Analogous conversion rates (/50 mg tissue.120 min) for human scalp skin were 0.2-0.4% and for human abdominal skin were 0.07-0.14%. Although dihydrotestosterone may be converted to androstanediol in peripheral tissues such as skin and prostate, our results suggest that the principal site of androgen conjugation to glucuronic acid is the liver. The present results cast doubt upon the role of androstanediol glucuronide as a specific marker of cutaneous androgen metabolism. PMID- 8473414 TI - Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients. AB - Circadian variations in serum TSH, especially its nocturnal rise, are often blunted in nonthyroidal illness. We analyzed TSH secretion in 15 diabetic patients (7 with type I and 8 with type II diabetes mellitus). Patients were evaluated when diabetes was poorly controlled (fasting blood glucose ranging from 13.7-19.2 mmol/L with absence of ketoacidosis) and after achieving glycemic control. Before correction of hyperglycemia, the nocturnal serum TSH peak (2230 0200 h) was abolished in 11 of 15 patients (73%); the mean (+/- SE) night TSH/morning TSH x 100 was 109.0 +/- 9.5 (range, 66.7-166.7) vs. a mean of 216.5 +/- 27.0 (range, 139.8-462.5) in normal controls. The mean morning TSH value in diabetics (1.9 +/- 0.4 mU/L) did not differ from that in normal age- and sex matched controls. The mean TSH increase after iv administration of TRH was only slightly reduced (8.4 +/- 1.2 mU/L pretreatment vs. 10.8 +/- 1.6 mU/L posttreatment), with the TRH test blunted in 3 cases. No differences were found between type I and type II patients. Correction of hyperglycemia was associated with the reappearance of a nocturnal TSH peak in all but 1 patient (mean TSH peak, 198.2 +/- 13.0; P = NS vs. controls). This change paralleled the normalization of serum total T3 and rT3, which were reduced and increased, respectively, when diabetes was poorly controlled. An inverse relationship was found between serum fructosamine levels and the nocturnal TSH peak, suggesting that metabolic decompensation accounts for the abolishment of the latter. PMID- 8473415 TI - Administration of an aromatase inhibitor during the late follicular phase of gonadotropin-treated cycles in rhesus monkeys: effects on follicle development, oocyte maturation, and subsequent luteal function. AB - Local modulation of follicular and gametogenic functions by ovarian androgens and estrogens in mammalian species has been proposed. This study examined the effects of elevated androgen/estrogen ratios during follicular maturation in vivo by inhibiting aromatase activity in rhesus monkeys. To obviate steroid feedback effects, gonadotropin-treated animals were used. Beginning at menses (day 1), animals received human (h) FSH (60 IU/day, im) on days 1-6, followed by hFSH plus hLH (60 IU/day, im) on days 7-9 to promote the growth of multiple follicles. Ovulatory maturation was induced by hCG (1000 IU, im) on day 10. On days 8-10, four animals received an aromatase inhibitor, 1,4,6-androstatrien-3,17-dione (ATD; 1-1.25 g, orally, twice/day), while five served as controls and received no further treatment. Within 8 h of ATD treatment, a 63% reduction in serum estradiol levels relative to control values was evident, which reached maximal suppression (84%) by day 10. A marked elevation (17-fold) in serum androstenedione and a lesser increase (2.6-fold) in serum testosterone occurred with aromatase inhibition, yielding androstenedione/estradiol (18.0) and testosterone/estradiol (1.9) ratios greater than those in controls (0.6 and 0.3, respectively). ATD treatment did not alter follicular diameters or the total number of follicles per animal (20 +/- 3) relative to control values (16 +/- 3). Of the total cohort classified, the proportion of oocytes collected at prophase I was greater (P < 0.05) after ATD treatment (31%) than in controls (11%). Completion of oocyte meiosis to metaphase II was retarded (P < 0.05) in ATD treated (4%) compared to control (26%) animals. Furthermore, the in vitro fertilization rate of metaphase II oocytes from ATD-treated animals (9%) was reduced (P < 0.05) relative to that in controls (25%). While basal progesterone production by luteinizing granulosa cells in vitro was similar between groups, the addition of hCG in vitro enhanced progesterone secretion by cells from ATD treated animals (3.1 +/- 0.3-fold over basal) to a greater extent (P = 0.05) than in controls (1.5 +/- 0.3-fold). Progesterone receptor was detected by immunocytochemistry in nuclei of luteinizing granulosa cells from ATD-treated animals as well as controls. Serum progesterone profiles and the length of the luteal phase were similar between groups. Thus, acute elevation of serum androgen/estrogen ratios in vivo during follicular maturation was detrimental to the gametogenic functions of the primate follicle, but did not alter follicular growth, events of early luteinization, or subsequent luteal function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8473416 TI - Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. AB - The purpose of this study was to investigate the roles of androgenic and estrogenic mechanisms in the stimulation of structural growth and plasma GH in male puberty. To resolve these two possible mechanisms, we compared the effect of two androgens in the treatment of constitutional delay in growth and adolescence: an aromatizable androgen, testosterone (T), and a nonaromatizable androgen, dihydrotestosterone (DHT). Nine adolescent males, Tanner stage 1 or 2, were studied before and during treatment with T enanthate (group A) or DHT heptanoate (group B). After 2.5 months of treatment, the height velocity (HV) was 12.6 +/- 2.8 cm/yr (n = 3) in group A and 8.9 +/- 1.7 cm/yr (n = 6) in group B, both within the range of peak HV for pubertal males. In group A, the integrated concentration of GH (ICGH) increased from 3.12 +/- 0.90 to 13.67 +/- 6.0 micrograms/L (P < 0.05), and plasma insulin-like growth factor-I (IGFI) increased from 126.7 +/- 2.5 to 350.3 +/- 20.3 micrograms/L (P < 0.01); plasma T increased from 0.8 +/- 0.5 to 33.8 +/- 11.0 nmol/L (P < 0.001), and the LH response to LHRH decreased from 27.6 +/- 10.7 to 5.9 +/- 2.5 IU/L (P = NS). In group B, ICGH decreased from 4.32 +/- 0.61 to 2.39 +/- 0.42 (P < 0.025), and IGF-I decreased from 218.3 +/- 39.2 to 184.0 +/- 15.8 (P = NS). Plasma T increased from 2.0 +/- 0.5 to 2.7 +/- 0.8 (P = NS), and the LH response to LHRH decreased from 45.7 +/- 14.5 to 10.7 +/- 5.8 (P < 0.05). To further evaluate the mechanism of the effect of DHT on plasma GH, seven male subjects with adolescent gynecomastia were treated with DHT heptanoate, and their responses were studied at 1 week and 3.5 months. ICGH decreased in conjunction with a decrease in the integrated T concentration (r = -0.77; P < 0.001) and to a slight degree with decreasing plasma estradiol (r = -0.39; P < 0.2). Plasma IGF-I did not show a significant change in the subjects with gynecomastia. Thus, the increase in GH at puberty in males appears to be due to an estrogen-dependent mechanism. The suppressive effect of DHT on GH secretion may be due to either suppression of estradiol production or a direct effect. Acceleration of HV into the peak pubertal range by DHT without an increase in plasma GH suggests that an increase in GH is not necessary for the pubertal growth spurt. PMID- 8473417 TI - Induction of a polarized micro-environment by human T cells and interferon-gamma in three-dimensional spheroid cultures of human endometrial epithelial cells. AB - Expression of human leukocyte antigen (HLA)-DR molecules and proliferation of epithelium in human endometrium are polarized. We have suggested that the induction of such a polarized micro-environment is T cell and interferon (IFN) gamma dependent. The present study was designed to demonstrate the induction of such a micro-environment around T cells and around the source of IFN-gamma. Spheroids reminiscent of endometrial glands were formed by allowing three dimensional aggregation of endometrial epithelial cells of a cloned HLA-DR negative endometrial carcinoma cell line (ECC1) over agarose. Both HLA-DR expression and inhibition of proliferation were found to be directly dependent on the dose of IFN-gamma that was allowed to diffuse in the agarose beneath the spheroids. To show that the interaction of the epithelial cells with activated T cells also induces HLA-DR molecules in a paracrine fashion in the epithelial cells, ECC1 spheroids were co-cultured with increasing numbers of allogeneic peripheral blood T cells for various time-intervals. T cells bound to the ECC1 cells, and became activated as indicated by the expression of interleukin (IL)-2 receptor and HLA-DR molecules. A focal HLA-DR expression became apparent in the ECC1 cells adjacent to the T cells. As the number of T cells added to spheroid cultures was increased, a concomitant increase in the number of HLA-DR positive ECC1 cells occurred and HLA-DR immunoreactivity was enhanced in each cell. There was a corresponding decrease in the proliferation of the ECC1 cells in T cell ECC1 spheroid co-cultures. Based on these data, we suggest that activation of T cells is associated with the induction of HLA-DR expression and inhibition of proliferation in a paracrine fashion in the epithelial cells and may be responsible for the creation of a polarized micro-environment in vivo. PMID- 8473418 TI - Effect of tamoxifen alone and in combination with RU 486 on the endometrium in the mid-luteal phase. AB - The effects of RU 486 combined with tamoxifen and tamoxifen alone on hormonal parameters and endometrial development at the time of implantation were studied. Measurements of cytosolic oestrogen and progesterone receptors in endometrium and placental protein 14 (PP14) in plasma were also included. Three dosage schedules were used: single oral dose of 40 mg tamoxifen alone and in combination with 200 mg RU 486, and 40 mg tamoxifen for three consecutive days starting on the first day after the luteinizing hormone (LH) surge. The combined treatment prolonged the luteal phase (P < 0.05) and increased the plasma levels of progesterone. A single dose of tamoxifen did not affect the bleeding pattern and plasma hormone levels, but raised plasma oestradiol and LH with the 3-day treatment. The endometrium was retarded after the combined and the 3-day treatment with tamoxifen. Concentrations of cytosolic progesterone receptors were higher after the combined therapy, but were unaffected after tamoxifen only. PP14 levels were higher (P < 0.05) after repeated tamoxifen doses than in controls, but were lower with combined treatment. Progesterone and oestrogen are evidently necessary for endometrial maturation during the secretory phase of the menstrual cycle. PP14 levels in plasma cannot be used for clinical assessments of endometrial function because high levels coincide with disturbed endometrial development. PMID- 8473419 TI - Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle. AB - The effects of continuous low dose mifepristone (RU 486) 10, 5 or 1 mg/day on the menstrual cycle were assessed in groups of five volunteers, who were treated for 30 days from the beginning of the cycle. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 22 29 of treatment were used to monitor the cycle. Pre- and post-treatment cycles presented a normal profile. During treatment, concentrations of RU 486 in plasma ranged from 65 nmol/l with 1 mg/day to 1000 nmol/l with 10 mg/day. With 10 or 5 mg/day, all treated cycles were prolonged as a result of arrested or slower follicular growth during treatment. Gonadotrophins, sex steroids and their urinary metabolites remained at early follicular phase levels throughout treatment, whereas androstenedione, prolactin and cortisol were unaffected. Follicular maturation resumed after discontinuation of treatment and several days later a luteinizing hormone surge followed by a luteal phase was observed in all cases. Ovulation was suppressed during treatment only in one of the five cycles treated with 1 mg/day. Endometrial maturation was disturbed by all doses. These data demonstrate a differential threshold of the follicle and the endometrium to mifepristone. This finding has potential application in the contraceptive field. PMID- 8473420 TI - Validation of the dual analyte assay of the oestrone:pregnanediol ratio in monitoring ovarian function. AB - The purpose of this study was to validate the dual analyte system (Boots Celltech Ltd, Slough, UK) as a marker of ovarian function. For this purpose the urinary profile of the ratio of oestrone-3-glucuronide to pregnanediol-3-glucuronide in urine (E13G/PD3G) was compared with plasma concentrations of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone from day 8-24 of the menstrual cycle in 23 women. Daily transvaginal ultrasound was also performed from day 8 of the cycle until sonographic evidence of follicular rupture. The ratio of urinary metabolites exhibited a maximum value close to ovulation. In the majority of cases this coincided with the day of LH peak, and was followed by follicular rupture within the next 24 h in 74% of cases. The assay gives a good marker of ovulation, however, it is unlikely to help in detecting the initiation of the fertile period or the quality of the menstrual cycle. PMID- 8473421 TI - A prospective study to evaluate the efficacy of modified swim-up preparation for male sex selection. AB - A previously published study reporting the use of a modified swim-up technique for sperm preparation prior to insemination which resulted in a high percentage of male births has been criticized for its lack of controls. The present prospective study was initiated to investigate further the efficacy of modified swim-up preparation for male sex-selection when applied in a properly defined control group. Our results showed that the proportion of males born in singleton pregnancies was approximately 50% in the group inseminated following sperm preparation with Percoll and in the control group with no sperm preparation compared with 88.5% in the group treated with the modified method of swim-up sperm preparation prior to insemination. This high rate of males in the group treated with modified swim-up was also observed in singleton pregnancies of women taking ovulation inducing drugs (primarily clomiphene citrate). This contrasts with previous publications in which a higher rate of females was found in clomiphene citrate patients using the albumin separation technique. How the mechanism of the swim-up procedure may result in a high male birth rate remains unclear. A high percentage of y enriched semen was found using fluorochrome quinacrine mustard staining but this procedure may falsely stain autosomal chromosomes. If analysis using sensitive DNA probes fails to confirm the y enrichment of the spermatozoa, one must hypothesize that the modified swim-up procedure damages the x-spermatozoa. PMID- 8473422 TI - Aetiology of congenital absence of vas deferens: genetic study of three generations. AB - Bilateral congenital absence of the vas deferens (CAVD) is a form of male sterility (found in otherwise normal men) of unknown aetiology. Because males with cystic fibrosis (CF) almost invariably have CAVD as well, we investigated the hypothesis that men with isolated CAVD might share a common genetic background with males with CF. Genetic testing for CF was carried out in three generations of subjects: 44 patients with CAVD and their wives, 24 of their parents, and 13 of their offspring generated by microsurgical epididymal sperm aspiration (MESA) and in-vitro fertilization (IVF). DNA extracted from peripheral lymphocytes was amplified by the polymerase chain reaction (PCR) and then analysed for 12 mutations in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene. Among 44 patients tested with CAVD, 26 (59%) were positive for at least one CF mutation, while the carrier frequency for CF mutations in the general population is only 4%. Four patients were found to be compound heterozygotes, three with genotypes Delta F-508/R117H, one with R553X/R117H. Among 24 parents tested, 15 (seven fathers, eight mothers) had sons with CAVD who were positive for CF mutations. Of these, nine (four fathers and five mothers) were found to be carriers for CF mutations. These four fathers, although carriers of CF mutations, were obviously fertile. Of the 13 offspring tested, six (three boys and three girls) had CF positive fathers. Of these, three (two girls and one boy) were found to be carriers for CF mutations. These MESA/IVF children are the first offspring to whom men with CAVD have been able to transmit CF mutations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473423 TI - Cytogenetic and morphological observations of single pronucleated human oocytes after in-vitro fertilization. AB - At 16-18 h after insemination, 5.5% of the inseminated oocytes displayed only one pronucleus. The incidence of single-pronucleated oocytes was not correlated with the age of the patient. Cytogenetic analysis of 41 embryos derived from single pronucleated oocytes revealed a haploid chromosome complement in 12.2%, a diploid chromosome complement in 80.5% and a triploid set in 7.3% of the embryos. In one diploid metaphase, a Y chromosome could be clearly demonstrated. A total of 312 single-pronucleated oocytes were evaluated twice (at 16-18 h and at 20-24 h after insemination). In 25% of the single-pronucleated oocytes a second pronucleus was observed 4-6 h later, suggesting asynchronous or delayed pronuclear formation. The cleavage of these embryos was similar to the cleavage of embryos with two pronuclei at the first evaluation. Parthenogenetic activation and asynchronous pronuclei may both be mechanisms leading to the morphological observation of a single pronucleus. In clinical practice, the second repeat observation of single pronucleated oocytes became part of the standard procedure. PMID- 8473424 TI - Lack of mutational alteration in the conserved regions of ZFY and SRY genes of 46,XY females with gonadal dysgenesis. AB - To further our understanding of the mechanism of action of regulatory and structural genes involved in human sex determination, we have examined three sex reversed 46,XY females and two of their normal fathers for any mutational alteration in ZFY and SRY genes, using polymerase chain reaction and single strand conformation polymorphism and by subsequent DNA sequencing. We could not find any mutation in the ZFY and SRY genes of these patients and their fathers. The results seem to suggest that although ZFY and SRY may be required for initiation of testis differentiation and male sex determination, sex-reversed females may predominantly result from alterations in genes either downstream or secondary to ZFY or SRY. PMID- 8473425 TI - Immaturity and chromosomal abnormalities in oocytes that fail to develop pronuclei following insemination in vitro. AB - A total of 293 oocytes that failed to develop pronuclei after insemination in vitro with apparently normal, fertile spermatozoa were obtained from 87 women undergoing therapeutic in-vitro fertilization. The oocytes were investigated cytogenetically to determine the incidence of immaturity and chromosomal abnormalities. Cytogenetic examination was possible in 81% of the preparations, in which immaturity and chromosomal abnormalities were present in 29.5 and 58.7% respectively. PMID- 8473426 TI - A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization. AB - The outcome of in-vitro fertilization and embryo transfer (IVF-ET) was compared in 76 patients with polycystic ovaries (PCO) diagnosed on pre-treatment ultrasound scan, and 76 control patients who had normal ovaries and were matched for age, cause of infertility and stimulation regimen. Despite receiving significantly less human menopausal gonadotrophin (HMG), patients with PCO, as compared with controls, had significantly higher serum oestradiol levels on the day of human chorionic gonadotrophin administration (5940 +/- 255 versus 4370 +/- 240 pmol/l, P < 0.001), developed more follicles (14.9 +/- 0.7 versus 9.8 +/- 0.6, P < 0.001) and produced more oocytes (9.3 +/- 0.6 versus 6.8 +/- 0.5, P = 0.003). However, fertilization rates were reduced in the PCO patients (52.8 +/- 3.4% versus 66.1 +/- 3.4%, P = 0.007). There was no significant difference in cleavage rates. The pregnancy rate/embryo transfer was 25.4% in the PCO group and 23.0% in the group with normal ovaries. There were three high order multiple pregnancies in the PCO group compared with none in the group with normal ovaries. Of the PCO patients, 10.5% developed moderate/severe ovarian hyperstimulation syndrome (OHSS) compared with none of the controls (P = 0.006). Patients with and without PCO undergoing IVF have comparable pregnancy and livebirth rates. However, it is important to diagnose PCO before ovarian stimulation is initiated as these patients are more likely to develop moderate or severe OHSS following IVF-ET. PMID- 8473427 TI - Comparative trial between an ultra-short and long protocol of luteinizing hormone releasing hormone agonist for ovarian stimulation in in-vitro fertilization. AB - A total of 312 patients with tubal infertility participated in a prospective randomized study comparing two regimens of ovarian stimulation with a luteinizing hormone-releasing hormone agonist (buserelin) and human menopausal gonadotrophin (HMG). Half of the patients were given an ultra-short treatment protocol when the agonist was administered on days 2, 3 and 4 of the stimulated cycles; the other half were given a long protocol when the agonist was administered from the mid luteal phase of the cycle preceding the treatment cycle. The mean number of HMG ampoules used per patient was significantly higher in the long protocol. No significant differences were found between the two groups in the incidence of cancelled cycles, failed oocyte recovery, mean number of oocytes recovered per patient, complete failure of fertilization and the fertilization and embryo cleavage rate. More patients undergoing the long protocol had supernumerary embryos cryopreserved and successful deliveries. PMID- 8473428 TI - Cervical leukocytosis and abnormal post-coital test: a diagnostic and therapeutic approach. AB - Inflammatory processes and cell-mediated immunological reactions in the cervix and vagina have been implicated as causal factors in some cases of infertility. This investigation examined whether cervical Papanicolaou (PAP) smears in combination with post-coital tests could reveal infertile patients with asymptomatic cervical leukocytosis. Women (n = 56) attending a hospital-based community infertility clinic were subjected to post-coital tests and simultaneous preparation of cervical PAP smears. Those women (n = 18) with both abnormal post coital tests and asymptomatic cervical leukocytosis, based on abnormally high numbers of leukocytes in the PAP smear, were randomly divided into two groups. One group (n = 10) received antibiotic therapy and the other (n = 8) received no therapy. In the treated group six women became pregnant within 3 months after treatment; none of the eight untreated patients became pregnant within the same period. These results suggest that cervical PAP smears, in cases with abnormal post-coital tests, are useful in detecting couples whose infertility may be due to simple, undetected, asymptomatic bacterial infections. PMID- 8473429 TI - The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study. AB - A cohort of 485 couples starting their first in-vitro fertilization (IVF) attempt between January, 1989 and February, 1991 inclusive, were followed until June 1, 1992. A total of 1086 treatment cycles were initiated (mean 2.2, range 1-6). Of these, 235 (21.8%) cycles were cancelled, giving a total of 851 embryo replacements (mean 1.7, range 1-5). After IVF treatment, 189 women have either delivered or have an ongoing pregnancy in the second or third trimester. This gives a baby take-home rate of 17.4% per started cycle and 22.2% per embryo replacement. For 91 (18.6%) of the couples, the treatment was abandoned prior to completion of the three scheduled IVF attempts and 57 (11.7%) of these had no completed IVF cycles. In the group of couples with reduced sperm quality, the delivery rate was significantly lower than that of the other groups. A total of 193 women had embryos cryopreserved in at least one IVF cycle; 124 of these women started a frozen embryo replacement cycle and 88 had at least one cycle with replacement of frozen/thawed embryos, resulting in 25 deliveries/ongoing pregnancies. Due to the Norwegian law on assisted procreation 65 (33.7%) of the women have had their frozen embryos thawed and discarded after 12 months of storage. The cryopreservation programme, with the limitations of the Norwegian law, gives a 5.2% increase in the baby take-home rate for women entering the IVF programme, an increase of 13.2% in the number of ongoing pregnancies/deliveries and an 11.6% increase in number of children/viable fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473430 TI - Acrosin activity in human spermatozoa in relation to semen quality and in-vitro fertilization. AB - Acrosin, a sperm proteinase released during acrosomal exocytosis, facilitates penetration through the oocyte vestments. The purpose of this investigation was to determine if a correlation exists between the acrosin activity of ejaculated human spermatozoa, before motility enrichment techniques, and in-vitro fertilization (IVF) success using selected (glass wool or swim-up) spermatozoa. Since all the oocytes were retrieved from women receiving exogenous hormonal stimulation and a mixed population of mature and immature oocytes were encountered, only cases with > or = 50% mature oocytes were analysed. Under these conditions, the acrosin activity was significantly greater (P < 0.01) in the ejaculates in which spermatozoa ultimately fertilized > or = 70% of the mature oocytes, than in the ejaculates in which spermatozoa ultimately fertilized < 70% of the mature oocytes. Furthermore, a strong correlation (r = 0.962, P = 0.0001) was detected between pre-IVF acrosin activity and subsequent high (> or = 70%) IVF success. Acrosin activity from normozoospermic and oligo-asthenozoospermic men was also compared and was significantly (P < 0.01) higher for the normozoospermic group. These data suggest that measurement of acrosin activity may be a valuable clinical laboratory assay for assessing the sperm fertilizing potential and that low acrosin activity is associated with abnormal semen characteristics. PMID- 8473431 TI - Lectin binding as a biological test in vitro for the prediction of functional activity of human spermatozoa. AB - Adequate acrosome reaction is one of the essential events that has to occur in successful mammalian fertilization. The purpose of the present study was to assess the acrosome reaction in human spermatozoa by means of iodine-labelled lectins concanavalin A and peanut agglutinin ([125I]Con A and [125I]PNA). Six sperm samples in the control (fertile) group were compared with 24 samples obtained from infertile patients. The acrosome reaction in both groups was induced in vitro by adding follicular fluid. Iodine-labelled lectins were bound to the sperm surface, and alteration in the binding capacity for [125I]PNA and [125I]Con A after induced acrosomal reaction was the main parameter for the prediction of acrosome reaction and fertilizing ability. It is hoped that with the availability of this test, in-vivo data may be accumulated. PMID- 8473432 TI - Development of embryos from natural cycle in-vitro fertilization: impact of medium type and female infertility factors. AB - Single embryos derived from natural cycle in-vitro fertilization (IVF) were graded during the pre-transfer culture period using morphological criteria. Most embryos developed well in culture with 96% showing continuing division and 68% showing good morphological appearance, although embryo quality tended to decline with an increased incidence of fragmentation and uneven cleavage as division proceeded. Both the pregnancy rate and the distribution of embryo grades were similar among four different culture media used, suggesting that choice of medium had little impact on outcome. In contrast, there were marked differences in pregnancy rate according to the type of infertility, which was not reflected in a decrease in embryo quality. However, although embryos from patients with tubal infertility implanted and formed viable pregnancies irrespective of morphological appearance, only 'good' quality embryos from patients with non-tubal (or 'unexplained') infertility were able to implant. Thus the appearance of the embryo derived from natural cycle IVF in women with unexplained infertility may be of clinical relevance. PMID- 8473433 TI - Requirement of preimplantation human embryos for extracellular calmodulin for development. AB - The objective of this study was to investigate the requirement for calmodulin in the cell division of the early human preimplantation embryo. Experiments using three agents capable of inhibiting calmodulin activity, N-(6-aminohexyl)-5-chloro 1-naphthalenesulphonamide (W7), W7 linked to agarose beads (W7-agarose) and calmodulin antibody, showed that W7 and calmodulin antibody arrested division of embryos in a dose-dependent manner. As W7 is able to penetrate the zona pellucida and enter the cells, calmodulin antibody can traverse the zona but not enter the cells and W7-agarose cannot traverse the zona, we have deduced that the calmodulin which appears relevant to embryo division may be both intracellular and intrazonal but not extrazonal. We conclude that calmodulin is specifically required for cell division in the early human preimplantation embryo and that the concentration of calmodulin surrounding the embryo within the zona is particularly important to embryo development. PMID- 8473434 TI - Steroid secretion by human early embryos in culture. AB - The ability of in-vitro fertilized human embryos to secrete oestradiol in culture in the presence of precursor androgen was demonstrated in four independent cultures. Varying amounts of oestradiol were detected and secretion was observed as early as days 5-8 post-fertilization. The pattern of human chorionic gonadotrophin secretion was similar to oestradiol secretion for individual embryos. In one additional culture, secretion of oestradiol and progesterone was observed. PMID- 8473435 TI - In-vitro development of in-vivo produced rhesus monkey morulae and blastocysts to hatched, attached, and post-attached blastocyst stages: morphology and early secretion of chorionic gonadotrophin. AB - The earliest time of secretion of chorionic gonadotrophin (CG) by primate embryos and its role during preimplantation development and implantation are not clearly determined. We cultured in-vivo fertilized/developed zona-intact, morphologically normal morulae (n = 11) and early blastocysts (n = 11), freshly recovered (by non surgical uterine flushing) on days 5 and 6 of pregnancy, respectively (day 0 = the day following LH surge), from non-superovulated naturally bred rhesus monkeys (Macaca mulatta). Embryos were cultured for a minimum of 24 days in dishes containing 1 ml of CMRL-1066 supplemented with 20% bovine fetal serum in a humidified atmosphere of 5% CO2 in air at 37 degrees C. The culture medium was changed every 48 h. The percentage of hatched blastocysts, developed from morulae and early blastocysts, was 90.9; elapsed times (mean +/- SEM) were 67.8 +/- 4.4 h (morula) and 37.8 +/- 3.6 h (blastocyst). The minimum number of Hoechst-stained cells/hatched blastocyst was 531. The mean diameter (+/- SEM) of cultured embryos increased from 180 microns at the beginning of culture to 374 +/- 28 and 450 +/- 19 microns at the fully expanded and hatched blastocyst stages, respectively. Hatched blastocysts continued to expand (maximum diameter: 1125 +/- 25 microns); after an additional 94-96 h they attached firmly to the serum-coated dishes and produced highly proliferating multinucleate trophectodermal cells, extending to a maximum diameter of 2-6 mm by 11-21 days of culture. Biologically active CG in embryo-grown, serial spent media samples was measured in a mouse Leydig cell bioassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473436 TI - Mouse embryo cleavage, metabolism and viability: role of medium composition. AB - The cleavage, metabolism and viability of mouse zygotes were assessed after culture in media of different ionic and metabolite composition. Medium with a high potassium concentration, characteristic of mammalian oviduct fluid, inhibited cleavage and blastocyst formation (P < 0.01). This inhibition was partially alleviated by the removal of phosphate, and subsequently abolished by supplementation with amino acids, vitamins, insulin, epidermal growth factor and transferrin (AVIET). Glucose uptake by cultured blastocysts, measured fluorimetrically, was not affected by the ionic or metabolite composition of the medium, but was significantly reduced by the inclusion of AVIET (P < 0.01). Lactate production was also significantly reduced in the presence of AVIET (P < 0.01). Calculations of metabolic activity revealed that embryos cultured in the presence of AVIET had a glycolytic activity similar to embryos developed in vivo. In contrast, embryos cultured in conventional embryo culture media exhibited an elevated glycolytic activity. Culturing embryos for 4 days in a reduced lactate concentration (4.79 mM), significantly increased fetal development after transfer, compared with embryos cultured in the concentration of lactate present in conventional embryo culture media (23.3 mM; P < 0.01). In contrast, when embryos were transferred on day 3 of culture, significantly more fetuses were obtained from embryos cultured in high levels of lactate (P < 0.01). Supplementation of medium with AVIET significantly increased resultant fetal weights after transfer (P < 0.05). This study demonstrates that different media are required to maintain embryo viability on successive days of culture, and highlights the potential limitations of employing simple salt solutions for the culture of preimplantation mammalian embryos. PMID- 8473437 TI - Preimplantation diagnosis of aneuploidy using fluorescent in-situ hybridization: evaluation using a chromosome 18-specific probe. AB - Fluorescent detection of in-situ hybridization (FISH) with a chromosome 18 specific probe (P5041 B.5 D18Z1) has been used to assess the use of this method for preimplantation diagnosis of aneuploidy. Interphase nuclei (n = 802) have been analysed from 59 normally fertilized embryos developing in vitro at the normal rate between days 2 and 7 postinsemination. The efficiency of hybridization in control cells, as assessed by the proportion with two signals in normal female lymphocytes was 88.9% (n = 353) and with three signals in a trisomic (48,XXX+18) fibroblast cell line 74.0% (n = 290). Fifty-four of the human embryos were considered to be diploid on the basis that the majority of nuclei had two signals. Some nuclei in these embryos had one or no signal, especially on day 2, and tetraploid nuclei were also widespread. Among the remaining five embryos, one 5-cell embryo on day 2 had three hybridization signals in 4/5 nuclei and was trisomic for chromosome 18, one 4-cell embryo on day 2 had only one signal in 4/4 nuclei and was monosomic, and the three other embryos were aneuploid mosaics and/or had multi-nucleated blastomeres. Analysis of the incidence of interphase nuclei with more or less than the diploid number of hybridization signals indicates that more than a single nucleus will be necessary for accurate preimplantation diagnosis of aneuploidy. PMID- 8473438 TI - Diagnosing sphingolipidoses in murine and human embryos. AB - The aim of this study was to diagnose lipid storage diseases in embryos at the preimplantation stage. Two parallel approaches were employed. Firstly, activities of several sphingolipid hydrolases were determined in extracts of murine embryos and also human oocytes and polyspermic embryos. Sensitive fluorescent or fluorogenic procedures provided indications that Tay-Sachs, Gaucher and Krabbe diseases might be diagnosed in one human blastomere, while for Niemann-Pick disease two might be required. Secondly, pyrene lipids were administered into murine embryos and their fluorescence was quantified by computerized imaging microscopy. As a model of Gaucher disease, the fluorescent substrate pyrene glucosylceramide was administered into murine embryos in the presence or absence of an inhibitor of the enzyme beta-glucosidase. Because of decreased degradation of the substrate in enzyme-inhibited cells, the fluorescence per blastomere was considerably greater relative to those which received no inhibitor. The results indicated that lipid storage diseases might be diagnosed in single human blastomeres at the preimplantation stage, obviating the need for pre-natal diagnosis and abortion of affected foetuses. PMID- 8473439 TI - Anti-endometrial and anti-endothelial auto-antibodies in women with endometriosis. AB - The present study investigates the specificity of anti-endometrial antibodies present in serum of women with endometriosis. A two colour indirect immuno histochemical method was used, so that the antigenic reactivity of endogenous immunoglobulins was blocked and specific anti-endometrial antibodies were readily distinguishable. Serum was collected from women with endometriosis, before and after 6 months of treatment, and from women without the disease. The reactivity of serum with uterine and ectopic endometrium from women with and without the disease was studied. The frequency of anti-endometrial antibodies in the serum of women with endometriosis was higher (P < 0.001) than in control sera. Most antibodies specifically reacted with glands in ectopic and uterine endometrium. Antibody reactivity was strongest with endometrium from control women, compared with uterine and ectopic endometrium from women with endometriosis (P < 0.01). A proportion of sera containing anti-endometrial antibodies also reacted with vascular endothelium. Binding was strongest to vessels in uterine and ectopic endometrium from women with endometriosis compared to endometrium from women without the disease (P < 0.01). The presence of anti-endometrial antibodies was associated with infertility. PMID- 8473440 TI - Endocrinology of in-vitro fertilization pregnancies during the first trimester. AB - The endocrine function of the corpus luteum and placenta and the inter relationships between ovarian steroids and the placental proteins in pregnancies achieved following ovarian stimulation, in-vitro fertilization and embryo transfer (IVF-ET) have been investigated. The serum concentrations of human chorionic gonadotrophin (HCG), Schwangerschaft protein-1 (SP-1), pregnancy associated plasma protein A (PAPP-A), progesterone and oestradiol were measured at weekly intervals between the 4th (ET plus 2 weeks) and 14th week of gestation in 86 pregnancies. The mean concentrations of the placental proteins and oestradiol were significantly higher in twin than in singleton pregnancies from as early as 5 weeks gestation, but the mean concentrations of progesterone were significantly higher only at the end of the first trimester. Ranking, as demonstrated by the presence of statistically significant correlations between serum levels of each substance analysed in week 13 with those of preceding weeks, was established for progesterone and SP-1 from the 5th week, for oestradiol and PAPP-A from the 7th week and for HCG from the 8th week of gestation. The presence of statistically significant correlations between each substance analysed suggests that the placenta becomes the dominant source of oestradiol from 8 weeks gestation and of progesterone not until 12 weeks gestation, and that the placental synthesis of HCG, SP-1, PAPP-A, oestradiol and progesterone appear to be linked. There were no statistically significant correlations between the serum concentrations of HCG and either progesterone or oestradiol until the production of each had become predominantly placental. PMID- 8473441 TI - Circulating placental protein 14: in the first trimester of spontaneous and IVF pregnancies. AB - Circulating placental protein 14 (PP14) levels were measured during the first trimester in three groups of pregnant women: (i) natural conception (n = 15); (ii) pituitary desensitization with buserelin and ovarian stimulation with human menopausal gonadotrophin (HMG) followed by in-vitro fertilization and embryo transfer (IVF-ET) (n = 15); and (iii) ovarian stimulation with clomiphene citrate and HMG, followed by IVF-ET (n = 16). A 7- to 8-fold increase in serum PP14 levels was observed in normal pregnancies between weeks 4 and 10. This increase was earlier and less marked in group (ii) and absent in group (iii). These findings support the concept that endometrial function is altered in pregnancies achieved following ovarian stimulation. Alternatively, if the ovary is an important source of PP14, then these data suggest that in contrast to ovarian synthesis of steroids and the peptide relaxin, ovarian stimulation results in an impairment of PP14 synthesis, and that this is most marked when clomiphene citrate has been used. PMID- 8473442 TI - Relationship of biochemical pregnancy to pre-ovulatory endometrial thickness and pattern in patients undergoing ovulation induction. AB - In order to assess the relationship between pre-ovulatory endometrial thickness and pattern and biochemical pregnancy, the pregnancy outcome was retrospectively analysed in 81 patients undergoing ovulation induction evaluated by vaginal ultrasound on the day of human chorionic gonadotrophin (HCG) administration or luteinizing hormone (LH) surge. Biochemical pregnancies occurred in 7/32 (21.9%) pregnancies when endometrial thickness was < 9 mm, compared to 0/49 when endometrial thickness was > or = 9 mm on the day of HCG administration or LH surge (P < 0.0025). Clinical abortions occurred in 5/32 (15.6%) pregnancies when endometrial thickness was 6-8 mm, compared to 6/49 (12.2%) when endometrial thickness was 6-8 mm (NS). Endometrial thickness was related to the cycle day of HCG or LH surge (r = 0.37, P < 0.001) but was unrelated to oestradiol level on the day of HCG administration or LH surge (r = 0.12). Biochemical pregnancies were related to endometrial pattern (r = -0.22, P = 0.02) but were unrelated to maternal age or previous abortions. Clinical abortions were related to age (r = 0.26, P = 0.01) and to previous abortion (r = 0.25, P = 0.013) but were unrelated to endometrial pattern. Neither biochemical pregnancy nor clinical abortion was related to oestradiol or LH levels on the day of HCG administration or LH surge. These findings suggest that the majority of biochemical pregnancies do not result from karyotypically abnormal embryos, as do clinical abortions. PMID- 8473443 TI - Ultrasound evidence for variability in the size and development of normal human embryos before the tenth post-insemination week after assisted reproductive technologies. AB - Differences in human chorionic gonadotrophin (HCG), average chorionic sac diameter, embryo/fetus crown-rump length and biparietal diameter were determined in 107 singleton pregnancies delivered after 34 weeks, whose post-insemination age was precisely known as a result of in-vitro fertilization (n = 28) or gamete intra-Fallopian transfer (n = 79). Crown-rump lengths were interpreted in relation to the developmental stage of the embryo. A 7-fold to 10-fold difference in HCG levels was observed on post-insemination days 13-16. A 2-fold to 3-fold difference occurred in average chorionic sac diameter on days 25-36. A 2-fold difference occurred in crown-rump length on seven of 10 days prior to day 44. Biparietal diameter differed by no more than 42% from day 57-68 and 20% after day 68. Chorionic sac diameter, crown-rump length, and biparietal diameter were also related to newborn weight. The results suggest firstly that marked differences occur in the rate of early human development, secondly, that the differences occur prior to day 27 when observable cardiac activity begins, and thirdly, that the differences are minimized after day 68 when the embryonic period of development is completed. PMID- 8473444 TI - Successful triplet pregnancy in a patient with a unicornuate uterus with a cavitary communicating rudimentary horn. AB - In a patient with primary infertility, ovulation was induced by monitored stimulation with human menopausal gonadotrophins (HMG) because of polycystic ovarian disease. Infertility work-up had shown a unicornuate uterus with a cavitary communicating rudimentary horn. The husband showed a varicocele-related moderate oligo-asthenoteratozoospermia. A triplet pregnancy occurred in a third HMG ovulation induction cycle combined with intra-uterine insemination of the husband's washed semen. The pregnancy was carefully monitored, and measures to prevent premature delivery were taken. Because of the patient's obvious discomfort in the presence of premature labour, Caesarean section was performed at 33 weeks gestation and three healthy infants were delivered. This is the first report of a successful triplet pregnancy in a women with a unicornuate uterus. The reproductive and obstetric outcome of this condition in general, and in the case of multiple pregnancy, is discussed. PMID- 8473445 TI - The techniques and complications of out-patient uterine washing in the assessment of endometrial function. AB - The complications of a consecutive series of 90 uterine washings performed among 52 women were studied. The amount of discomfort was significantly less than that of endometrial biopsy but greater than that of cervical smear or blood sampling. Incomplete recovery of fluid (< 8 ml from 10 ml flushing fluid) was reported in only 3% of cases. Vaginal bleeding, pelvic infection and delayed abdominal pain were not encountered. The techniques of uterine washing are simple and may have important implications in the study of endometrial function. PMID- 8473446 TI - Management of suboptimal sonographic endometrial patterns in patients undergoing in-vitro fertilization and embryo transfer. AB - A total of 816 women who underwent 1332 cycles of ovarian stimulation for in vitro fertilization and embryo transfer (IVF/ET) had sonographic assessments of the endometrium within 2 days of oocyte retrieval. Endometrial linings were classified on the basis of thickness and echogenicity, using a grading system described previously. Grades I and IIB ('poor') were associated with a 6% viable pregnancy rate (advanced beyond 12 weeks' gestation) compared with a 29% rate for Grade IIA ('optimal'). In a subset of 112 women with poor endometrial linings during natural cycles, eight out of 21 women (38%) under 40 years of age developed optimal linings following ovarian stimulation with menotrophins, while 19 out of 91 women (21%) aged 41-45 years converted to optimal linings. Twenty two out of 47 women (44%) who failed to develop optimal endometrial linings following ovarian stimulation converted to Grade IIA during subsequent cycles of exogenous oestrogen replacement. The financial, emotional, and physical burden associated with IVF/ET demands that patients with poor endometrial linings following ovarian stimulation with menotrophins be counselled with regard to either cancelling their cycles of treatment, or having their embryos cryopreserved for transfer to the uterus during a subsequent hormonal replacement cycle. PMID- 8473447 TI - Treatment with naltrexone in hypothalamic ovarian failure: induction of ovulation and pregnancy. AB - Sixty-six women suffering from various grades of hypothalamic ovarian failure were treated with the opiate antagonist naltrexone at doses ranging from 25 to 150 mg per day. This treatment resulted in complete normalization of the menstrual cycle in 49 of 66 patients, as indicated by the pattern of circulating levels of gonadotrophins and ovarian steroids. Five patients failed to respond, three of whom were suffering from primary hypothalamic amenorrhoea. In patients who responded to the administration of naltrexone, there was a dramatic increase in the amplitude and frequency of gonadotrophin pulses, reflecting disinhibition of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator. Eighteen pregnancies were achieved in 16 women who were also treated for infertility, resulting in a cumulative pregnancy rate closely resembling that of a normal population. There were only minor side-effects that could be attributed to the drug. These data demonstrate that chronic administration of an opiate antagonist will normalize ovarian function in women suffering from different grades of hypothalamic ovarian failure. The data therefore support the view that suppression of the activity of the hypothalamic pulse generator, that directs GnRH release, is mediated by endogenous opioids. Also, that hypothalamic ovarian failure is the consequence of an inappropriate increase in opioid tone impinging on neurons that release GnRH in a pulsatile manner into the pituitary portal circulation. PMID- 8473448 TI - Endocrine changes and clinical outcome after laparoscopic ovarian resection in women with polycystic ovaries. AB - Ovarian laparoscopic resection was applied to 23 sterile patients affected with polycystic ovarian disease (PCOD) resistant to different pharmacological treatments, in order to induce ovulation. After resection, 56% of the patients had spontaneous ovulatory cycles and 13 pregnancies arose. Ten of the pregnancies were spontaneous and three followed treatment with clomiphene. Hormone changes were assessed in 15 patients, including five with spontaneous menstruation but without ovulation and five with persistent amenorrhoea for 3 months after resection. A significant decrease in both androstenedione and testosterone levels occurred in all patients. These decreases were not related to the clinical results of resection. Luteinizing hormone (LH) did not vary greatly in any group after resection. Mean values and mean pulsatility of follicle stimulating hormone (FSH) increased significantly only in pregnant patients or those with spontaneous ovulatory cycles. The results of gonadotrophin-releasing hormone (GnRH) assays did not change after resection. The mechanisms involved in the resumption of cyclic function of the hypophyseal-ovarian axis after resection are discussed briefly. PMID- 8473449 TI - Sandostatin has no direct effect on ovarian steroidogenesis in vitro. AB - Rat granulosa and theca-interstitial cells from immature, oestradiol-treated rats were isolated and incubated for 144 h with follicle stimulating hormone (FSH), luteinizing hormone (LH), insulin alone or in combinations, and with two doses of sandostatin (10(-7) M and 10(-6) M per culture). Oestradiol and testosterone production by granulosa and theca-interstitial cells, respectively, was measured in culture media. The stimulatory effects of FSH alone and FSH with insulin but not insulin alone on oestradiol production by granulosa cells were observed. Similarly, increased testosterone concentrations after treatment with LH alone and LH with insulin but not insulin alone were found in media from theca interstitial cells. The addition of high or low doses of sandostatin to the cultures did not affect the production of oestradiol or testosterone. It was concluded that sandostatin does not exert any direct effect on ovarian steroidogenesis in vitro. PMID- 8473450 TI - Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study. AB - The effect of doubling the human menopausal gonadotrophin (HMG) dose in the same treatment cycle in which the ovarian response after 5 days of ovarian stimulation with 225 IU/day is 'low', has been evaluated in a prospective randomized study. Forty-six patients met the ultrasound and oestradiol criteria for enrollment in the study, one patient participated twice. In 22 patients treatment was continued with 225 IU HMG/day and in 25 patients the HMG dose was increased to 450 IU/day. No effect of doubling the HMG dose was found on the length of the ovarian stimulation, peak oestradiol values, number of follicles > or = 11 and > or = 14 mm in diameter respectively on ultrasound on the day of HCG administration, number of cancelled cycles, number of oocytes at follicular puncture and the number of patients with < or = 3 oocytes at retrieval. It is concluded that doubling the HMG dose in the course of an IVF treatment cycle is not effective in enhancing ovarian response in low responders. This is in accordance with current theories on follicular growth, which state that follicular recruitment occurs only in the late luteal and early follicular phase of the menstrual cycle. PMID- 8473451 TI - Is the measurement of oestradiol/progesterone ratios in the peri-implantation period of any value in predicting endometrial development? AB - To examine the value of the measurement of oestradiol/progesterone ratios in the peri-implantation period, three different types of cycle were studied; natural cycles (n = 13), cycles treated with anti-oestrogens (n = 19), and artificial cycles (n = 41) produced by six different hormone replacement regimens. Normal endometrial development was found to occur across a wide range of oestradiol/progesterone ratios. There was no significant correlation between the oestradiol/progesterone ratios and results of endometrial dating. The results suggest that oestradiol/progesterone ratios are of limited value in predicting endometrial development at the time of implantation. PMID- 8473452 TI - Impact of gonadotrophin dose on pre-embryo recovery and development in superovulated mice. AB - A dose-response analysis was performed by stimulating mice with Humegon, which contains approximately equal amounts of follicle stimulating hormone (FSH) and luteinizing hormone (LH). The effect of increasing stimulation was assessed by monitoring the number and developmental stages of pre-embryos flushed from the tubes, and the developmental potency of these pre-embryos after culturing for 72 h. Increasing the stimulation doses resulted in an increased recovery of 2-cell pre-embryos. A maximal plateau of 40-50 2-cell pre-embryos was reached after stimulation with 15-30 IU FSH/LH. Higher stimulation doses up to 50 IU FSH/LH showed no further increase in pre-embryo recovery. Increased stimulation doses did not affect the number of 1-cell pre-embryos or the number of pre-embryos which developed further than the 2-cell stage. An average of 88 +/- 1.7% of the flushed pre-embryos were 2-cell pre-embryos. The fraction of flushed pre-embryos which developed into blastocysts after 72 h of culturing was constant at all stimulation doses, with an average of 81 +/- 1.9%. A maximal plateau of 35-40 blastocysts was reached after stimulating with 15-30 IU FSH/LH. The group of pre embryos at less advanced developmental stages and the group of degenerated pre embryos showed a small but dose dependent increase in number. In conclusion, we found that increasing doses of Humegon resulted in an increased recovery of pre embryos capable of preimplantation development. This increased recovery occurred despite the high level of LH contained in this FSH/LH stimulation. PMID- 8473453 TI - A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception. AB - A prospective randomized study was conducted at the Family Planning Association of Hong Kong to compare the efficacy of the Yuzpe regimen and levonorgestrel (0.75 mg for two doses 12 h apart) in post-coital contraception. A total of 424 subjects were recruited into the Yuzpe group and 410 subjects into the levonorgestrel group; 77 subjects in the Yuzpe group and 79 subjects in the levonorgestrel group had further acts of intercourse during the treatment cycle. Fifteen pregnancies (3.5%) occurred in the Yuzpe group and 12 pregnancies (2.9%) in the levonorgestrel group. After excluding the patients who had further acts of intercourse, the failure rates in the Yuzpe group and the levonorgestrel group were 2.6 and 2.4% respectively. The incidence of nausea, vomiting and fatigue in the Yuzpe group was significantly higher than those in the levonorgestrel group. We conclude that levonorgestrel is an effective drug for post-coital contraception with a lower incidence of side-effects than the Yuzpe regimen. PMID- 8473454 TI - Improvement of clinical pregnancy rate and implantation rate of in-vitro fertilization-embryo transfer patients by using methylprednisone. AB - A prospective non-randomized study was undertaken to test whether immunosuppression improves implantation and pregnancy rates in an in-vitro fertilization-embryo transfer (IVF-ET) programme in patients with tubal factor infertility. Treatment involved ovarian stimulation, transvaginal oocyte retrieval, IVF-ET, and assessment of short-term administration of large doses of corticosteroids (60 mg of methyl-prednisone x 4 days). When compared to the group that did not receive immunosuppressive doses of methylprednisone (group A; mean age 31.85 +/- 4.09 years), those subjects who were treated (group A2) showed a statistically significant increase in pregnancy (P < 0.01) and take home baby rate (P < 0.01). Similar results were observed in subjects who received corticosteroids in their first IVF-ET attempt (group B; mean age 34.32 +/- 4.98 years). Our results suggest that immunosuppressive doses of corticosteroids administered for a short period of time to patients undergoing IVF-ET could significantly improve the implantation and pregnancy rates. Possible mechanisms of action of corticosteroids are proposed. PMID- 8473455 TI - Psychosocial impacts of infertility on Greek couples. AB - Psychosocial impacts of infertility were investigated in couples undergoing different treatment procedures in our clinic. Couples were interviewed in a semi structured way by a psychologist or a psychiatrist and responded to three specially structured questionnaires: the Life Events Scale, the Marlowe Crowne/Taylor Scale and the Side Effect Checklist. The data were analysed in terms of demographic characteristics as well as treatment procedure. The psychosocial, psychosexual and emotional outcomes of their infertility problem and Greek traditional culture laws are discussed. Stress has been identified in both sexes, depression mostly in women, while men showed a tendency towards repressed anxiety and thus a greater risk of psychosomatic illness, a finding supported by their response to the Side Effect Checklist. Women showed a high defensive anxiety and also reported numerous psychosomatic symptoms. These couples seem to have special needs and fears, both general and treatment specific. Very few of our couples would be considered as severely emotionally disturbed. Women seem to have more difficulties in social adjustment. Sexual dysfunction was reported by almost half of our subjects, although this was associated with a degree of deterioration in their marriage. Guilt feelings, particularly connected with previous abortions, seem to be torturing most women. Finally, both partners seem to have psychological problems irrespective of the one in whom the aetiological problem was found. Moreover, traditional rules seem to impose a special burden on people coming from rural areas. Our results strongly support the belief that infertile couples undergoing different treatments need psychological counselling and supportive psychotherapy. PMID- 8473456 TI - Characterization of abnormal one pronuclear human oocytes by morphology, cytogenetics and in-situ hybridization. AB - The morphology, chromosomal constitution and developmental capability of abnormal human oocytes (94/3500 oocytes; 2.7%) which after insemination exhibited only one pronucleus were examined. The majority of one pronuclear oocytes exhibited two or more distinct polar bodies. Dividing oocytes showed irregular chromosome distribution from haploid to diploid. Embryos resulting from abnormal oocytes displayed limited developmental potential. Many of them underwent fragmentation or were arrested at the 2- or 8-cell stage of development, and only some reached the morula or blastocyst state (11/35 oocytes). In approximately 45% (15/33) of examined oocytes, decondensed sperm heads or tiny nucleus-like structures were found in addition to a single nucleus. Chromosome Y was also detected in chromosomal preparations in approximately 10% of the oocytes by in-situ hybridization utilizing the human Y chromosome-specific DNA probe (DYZ3). These observations provided strong evidence that many of these oocytes originated from fertilized oocytes. The origin of the other one pronuclear oocytes could not be determined. Parthenogenetic activation of some oocytes cannot be excluded and other explanations concerning the origin of abnormal oocytes are discussed. PMID- 8473457 TI - Tumour necrosis factor alpha and interleukin 2 in normal and infected human seminal fluid. AB - The presence of cytokines such as the tumour necrosis factor alpha (TNF alpha) and interleukin 2 (IL2) in human spermatozoa is still to be defined. The aim of this study was to measure the concentration of both soluble factors in seminal fluid. Data from normal semen samples (n = 24) confirmed the presence of IL2 (258 +/- 84 fmol/ml corresponding to 953 +/- 369 fmol/total volume of ejaculate) and TNF alpha (62.2 +/- 16.4 fmol/ml corresponding to 231.3 +/- 86 fmol/total volume of ejaculate). A significant positive correlation (r = 0.59; P < 0.01) was observed between the TNF alpha and the IL2 concentrations. The concentrations of these cytokines were not related to sperm parameters. In contrast, IL2 concentrations (196.9 +/- 60.4 fmol/ml; 686.2 +/- 236.7 fmol/total volume of ejaculate) evaluated in 16 seminal fluids with identified bacterial agents were lower than in the control group, whereas TNF alpha concentrations (68.6 +/- 12.3 fmol/ml; 241.3 +/- 78.9 fmol/total volume of ejaculate) were not significantly different from the controls. Further studies are needed to determine the potential role of these cytokines in the physiology of semen and their usefulness as indicators of reproductive pathology. PMID- 8473458 TI - Acrosome reactivity in spermatozoa of different morphology in response to stimulation with follicular fluid. AB - The ability of the morphologically abnormal spermatozoon to undergo the processes necessary for fertilization is unknown; one of the essential processes is the acrosome reaction. In order to assess this, spermatozoa from 10 known fertile donors were incubated with either follicular fluid or Earle's medium containing 3 mg/ml bovine serum albumin at 37 degrees C for 6 h. The spermatozoa were then stained with 2% Trypan Blue prior to being fixed in glutaraldehyde and stained for the presence of the acrosomal cap using the triple stain. Fifty live spermatozoa in each of four morphological categories (normal head, large head, small head, abnormal neck or tail) were examined and the number of acrosome reacted spermatozoa determined. There was a significant difference between the morphological groups in the baseline number of acrosome-reacted spermatozoa, determined by examining sperm samples incubated in Earle's medium; however, the number of spermatozoa undergoing the acrosome reaction in response to stimulation with follicular fluid (i.e. the number of spermatozoa acrosome-reacted in follicular fluid minus the number acrosome-reacted in Earle's medium) was similar for all morphological groups. This suggests that abnormal sperm morphology did not affect the response of spermatozoa to activation of the acrosome reaction by exogenous stimuli. PMID- 8473459 TI - Ultrastructural observations on the entry of Chlamydia trachomatis into human spermatozoa. AB - Chlamydia trachomatis infections are an important problem in human reproduction and family planning. In this study, the significance of chlamydial infection in male infertility and artificial insemination has been investigated. Electron microscope observations on male ejaculates have revealed the presence of the elementary and reticulate body forms of C.trachomatis in spermatozoa. Furthermore, the entry of the elementary body into the human spermatozoon head has been demonstrated. After the passage of the infectious elementary body into the nucleus, all stages of reticulate body formation in the head of the spermatozoon were detected. According to ultrastructural findings, C.trachomatis not only adhered to but also penetrated into the tail structure. Thus two different functional and morphological forms of C.trachomatis can infect and be transmitted by spermatozoa and may cause infertility. PMID- 8473460 TI - Two pregnancies after in-vitro fertilization with spermatozoa from alloplastic spermatocoeles. AB - Two case reports describe successful in-vitro fertilization (IVF) of oocytes of two 28-year-old women with epididymal spermatozoa aspirated from alloplastic spermatocoeles of the husbands. Both men suffered from complete ejaculatory failure, which was caused by paraplegia in the first and by radical surgery of an embryonic carcinoma of the testis in the second. Motile spermatozoa were aspirated in the first case 4 months after implantation of the spermatocoele, and in the second at 1 month. For the first couple, IVF treatment led to a singleton pregnancy; the child has since been born. In the second couple, IVF treatment resulted in a twin pregnancy, with intra-uterine abortion of one gestational sac. The resulting singleton pregnancy is still ongoing. PMID- 8473461 TI - Synergistic effect of TEST--yolk buffer treatment and glass wool filtration of spermatozoa on the outcome of the hamster oocyte penetration assay. AB - Enhanced penetration of zona-free hamster oocytes occurs after spermatozoa have either been treated with TEST--yolk buffer or processed by glass wool filtration. The present study was conducted to determine if a synergistic effect on fertilizing ability could be achieved by combining these two treatments. Ejaculates (n = 16) were treated with TEST--yolk buffer (TYB) and divided into two aliquots. One aliquot was kept as control and the other aliquot was filtered through glass wool prior to the sperm penetration assay. The TYB--glass wool filtered spermatozoa penetrated a significantly higher percentage of oocytes than the TYB treated spermatozoa. PMID- 8473462 TI - Purification of a factor from human peritoneal fluid that is able to immobilize spermatozoa. AB - Human peritoneal fluid has been claimed to influence sperm motility. This report gives evidence for the presence in midcycle peritoneal fluid of a protein-bound, lipidic (hydrophobic) component able to immobilize spermatozoa as a function of time. This component was extracted from molecular weight-sieving and ion exchange/high pressure liquid chromatography (HPLC)-purified peritoneal fluid fractions by either chloroform/methanol or charcoal treatments; resuspension of the chloroform/methanol extract with BWW-buffer and subsequent testing on spermatozoa resulted in sperm immobilization. Sequential or step-down chromatographic procedures (molecular weight-sieving-->cation-exchange-->anion exchange HPLC separations of native peritoneal fluid) and extensive dialysis against double distilled water allowed the purification of the sperm immobilizing factor, as evidenced by the shorter incubation times necessary for sperm immobilization. Furthermore, the active fraction was found to immobilize spermatozoa without affecting its viability. Separation of the chloroform/methanol extracted immobilizing fraction on thin layer chromatography under conditions for phospholipid detection allowed the identification of a characteristic band which, after re-extraction, was found to be the sperm immobilizing substance. This factor does not contain choline, ethanolamine or serine. These results suggest that some lipidic peritoneal fluid components may influence sperm motility. PMID- 8473463 TI - The effect of three anti-oestrogen drugs on cervical mucus quality and in-vitro sperm-cervical mucus interaction in ovulatory women. AB - The anti-oestrogens, clomiphene citrate, tamoxifen and cyclofenil are commonly used in the treatment of female infertility. Their role in the management of anovulation is well established but there is continuing controversy about their relevance to other areas of management. We have studied the effects of each of these drugs on cervical mucus and sperm-cervical mucus interaction among 23 patients with unexplained infertility. Each patient received all three drugs in an alternative month treatment regime and in addition acted as her own control. The starting point in each patient was randomized. Luteinizing hormone (LH) and oestradiol were measured daily from day 10, and follicle scanning was also undertaken. Cervical mucus quality and sperm-cervical mucus interaction were studied on the day of onset of the LH surge. The use of clomiphene and tamoxifen resulted in a significant reduction in cervical mucus score and sperm-cervical mucus interaction as judged by the distance travelled by the vanguard spermatozoa. Cyclofenil had no effect on these parameters. PMID- 8473464 TI - Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy--a prospective study. AB - A prospective study was conducted on the incidence of intra-uterine pathology diagnosed by hysteroscopy in 147 women who underwent dilatation and sharp curettage due to spontaneous first trimester abortion. The diagnostic hysteroscopies were performed 4-6 weeks after the miscarriage, using CO2 as medium for uterine distention. In 38 patients (25.9%), uterine pathology was found, of whom 28 patients (19%) had intra-uterine adhesions (IUA). The incidence of IUA following only one abortion was 16.3% (16 out of 98 cases), all were of mild extent and filmy consistency, occupying less than one-quarter of the uterine cavity. The incidence of IUA after two abortions was 14% (3/21) but the incidence after three or more spontaneous abortions was significantly elevated (32%, 9/28), (P < 0.05, chi-square test). In addition, 58% of IUA diagnosed in the latter two groups were of a more severe extent. After a first miscarriage, occurrence of post-abortion IUA was not related to the serum oestrogen concentration on the day of curettage, nor was it related to any of the oestrogen treatment modalities used in this study. Although in most of these cases normal recovery of the endometrium was the rule, the high incidence of IUA diagnosed in this prospective study stresses the need for preventive treatment and close follow-up of patients after sharp curettage due to spontaneous abortion. Obviously oestrogen treatment alone did not prove to be effective and other treatment methods should be evaluated. The high incidence and severity of IUA in habitual aborters clearly justifies the performance of a diagnostic hysteroscopy as a standard evaluation. PMID- 8473465 TI - Transcervical falloposcopy: preliminary experience. AB - The new technique of endoluminal tubal exploration was evaluated by performing transcervical falloposcopy instead of chromoperturbation under control of concurrent laparoscopy. In this feasibility study, catheterization was performed with the use of either a transhysteroscopic or a free-hand tubal cannulation technique. A total of 66 patients were investigated for primary or secondary infertility with proximal and/or distal suspected tubal defects on the basis of prior hysterosalpingography; three patients were investigated for unruptured tubal pregnancy; two patients were investigated to localize the tip of the tubal embryo transfer catheter. Transcervical catheterization was successful in 110 of the 130 tubes (84.6%). Successful and informative falloposcopy was achieved in 30% of the 110 cannulated tubes. The transcervical free-hand cannulation technique was as effective as the transhysteroscopic approach. Recanalization of at least one tube was achieved in 83% of women with proximal obstruction. Tubal cannulation by the tubal embryo transfer catheter was confirmed by falloposcopy in the two cases where free-hand catheterization was used. This study confirms that it is possible to visualize the tubal lumen and demonstrates that the free hand cannulation technique is a simple and effective alternative to the transhysteroscopic approach. However, further progress in catheter technology has to be achieved in order to perform regularly successful transcervical falloposcopy in damaged tubes. PMID- 8473466 TI - Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata. AB - To determine whether pre-operative treatment with gonadotrophin-releasing hormone (GnRH) analogue may have a beneficial effect on surgery outcome, 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy (TAH), were randomly divided into a study group (n = 29) and a control group (n = 24). The study group of patients were treated by an i.m. injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery. The control group had no pre-operative treatment. Haemoglobin concentration and oestradiol, follicle stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery, and at surgery. The duration of surgery was shorter in the study group (49 versus 70 min in the hysterectomy group) and intra operative blood loss was less (208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies). Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery, and diminishing the intra-operative blood loss in surgery for fibroid uteri. Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri. PMID- 8473467 TI - Sperm/egg binding patterns and oocyte cytology in retrospective analysis of fertilization failure in vitro. AB - Failures of fertilization in in-vitro fertilization have been often linked to visually recognizable defects in spermatozoa, and occasionally to anti-sperm antibodies. However, some total failures and the frequent lack of fertilization in some eggs of normal appearance (partial failure) often remain unexplained. Simple evaluation of the configuration of sperm binding to the zona pellucida and of the oocyte features revealed by acetic alcohol fixation and lacmoid staining, may provide diagnostic clues in this respect. Among 25 cases of unanticipated total failure, this approach identified some men with normal semen analyses whose spermatozoa displayed either a total inability to bind to the zona or, after binding, an inability to intrude into the zona matrix. However, in 10 of these cases significant numbers of spermatozoa were bound to and intruded deep into the zona, a pattern consistent with the possibility of an egg defect, specifically a resistance to the passage of spermatozoa past the inner portion of the zona pellucida. Such a block also appeared to be the main cause of fertilization failure among 442 unfertilized eggs from 154 partial failure patients. As in the total failures, the inability of apparently competent spermatozoa to penetrate the zona was often associated with ooplasmic anomalies (refractile bodies, extra groups of chromosomes, chromatin rings or masses, one or more pronuclei with one or no polar bodies, and other occasional anomalies). These anomalies occurred in 79.4% of this unfertilized oocyte subset, in contrast to a 27.4% incidence in 238 oocytes not fertilized because of sperm defects. Simple retrospective assessment of sperm binding patterns and oocyte cytology can be a valuable complement to semen analysis in diagnosis of fertilization failure in vitro. PMID- 8473468 TI - Zona opening with 308 nm XeCl excimer laser improves fertilization by spermatozoa from long-term vasectomized mice. AB - Spermatozoa from long-term vasectomized mice have greatly reduced fertilizing ability in vivo and in vitro, which makes this a useful animal model for male factor infertility. The purpose of this study was to evaluate the 308 nm XeCl excimer laser for opening the zona pellucida to enhance the fertilization rate with spermatozoa from vasectomized males. Inseminating zona-intact (control) oocytes with 5 x 10(6) spermatozoa/ml resulted in only 6% fertilization and 33.3% development to the blastocyst stage; zona-opened oocytes showed significant improvement with 31.5% fertilization, 90% cleavage to the 2-cell stage, and 72.2% blastocyst formation. Out of the 130 oocytes in the experimental group, zona ablation was performed successfully on 127 and only three were damaged. These results suggest that laser micromanipulation for assisted fertilization potentially offers a simplified and precise method for mechanical zona cutting. PMID- 8473469 TI - Repeated sperm injection under the zona following initial fertilization failure. AB - When fertilization fails following micromanipulative under-zona insemination, it is possible to repeat the procedure adding more spermatozoa to achieve fertilization, embryonic development and pregnancy. We report on 18 human in vitro fertilization cycles where this approach was used. In nine cycles only late fertilized embryos were available for transfer, and these gave rise to two viable pregnancies (22.2% per transfer). In six cycles, where a mixture of late- and timely fertilized embryos were available for transfer, two viable pregnancies arose (33.3% per transfer). In three cycles no fertilization was achieved even after reinsemination by repeated under-zona insemination. PMID- 8473470 TI - Cytogenetic sexing of mouse embryos. AB - Cytogenetic sexing by means of chromosome C-banding was carried out in 1/2 and 2/4 biopsied mouse embryos. Chromosome spreads were obtained in 85.0% of 1/2 embryos and in 77.5% of 2/4-embryos. Sexing was accomplished in 30.0% of 1/2 embryos and 52.5% of 2/4-embryos, with a loss due to poor technique of 12.5 and 15.0% respectively. Transfer of sexed embryos resulted in a low implantation rate. The two live fetuses obtained were of the predicted sex. PMID- 8473471 TI - Expression of integrins by human trophoblast and differential adhesion to laminin or fibronectin. AB - The process of placental implantation involves a series of transformations of trophoblast from a single polarized epithelial layer resting on a basement membrane (villous trophoblast), to cellular aggregates (trophoblast columns) which ultimately disperse to invade uterine decidua as individual cells (interstitial trophoblast). Such tissue re-modelling is associated with changes in the constituents of the extracellular matrix and in the expression of matrix receptors by the cells, the most relevant being the family of integrins which bind to laminin and fibronectin. In this study we show, by immunohistology and flow cytometry, a gradual loss of laminin receptors with the concomitant acquisition of fibronectin receptors as trophoblast is transformed from the villous phenotype, through the cell columns, into the extravillous population. The pattern of staining for the alpha 5, alpha 6, beta 1 and beta 4 subunits indicates that the integrins expressed by trophoblast are predominantly the alpha 5 beta 1 and the alpha 6 beta 4 heterodimers. We have also shown that isolated trophoblast cells assume a flattened, sessile phenotype when cultured on laminin but exhibit a more spreading, motile morphology when plated on fibronectin. In addition, numerous multinucleated giant cells are observed on a fibronectin substrate. Our data suggest that the relative expression of laminin and fibronectin receptors may determine the morphology and behaviour of trophoblast during the process of implantation. PMID- 8473472 TI - Serum placental protein 14 concentrations in the first trimester of ovum donation pregnancies. AB - The concentration of the endometrial glycoprotein placental protein 14 (PP14) has been measured at weekly intervals during the first trimester in serum obtained from women who had become pregnant naturally (n = 15, all singleton) or following ovum donation (n = 16, 15 singleton and one twin) after ovarian failure (n = 13), Turner's syndrome (n = 2) or post-chemotherapy (n = 1). The concentration of PP14 failed to rise in ovum donation pregnancies, and was significantly reduced compared to the concentration in natural conceptions from 5 to 13 weeks gestation (P < 0.05-0.01). These findings demonstrate that the corpus luteum is essential for the normal increase in serum PP14 in the first trimester. Furthermore, they suggest that progesterone is not the major stimulus to PP14 synthesis in early pregnancy. PMID- 8473473 TI - Oocyte donation in menopausal women aged over 40 years. AB - In order to investigate the pregnancy potential of menopausal women over 40 years of age by use of donor eggs, we retrospectively analysed the results of our ovum donation programme. Forty-one clinical pregnancies were established in 134 recipient cycles. The recipients were divided into three age groups (40-43, 44-47 and > or = 48 years) in order to investigate the implantation rate with respect to age. The 30.6% pregnancy rate per embryo transfer cycle and 9.7% implantation rate per embryo appeared to be constant in all age groups studied. Fourteen pregnancies ended in miscarriage, there was one ectopic pregnancy and 25 healthy babies have been delivered. The oldest woman to deliver was 54 years of age. This report highlights the question of age limit for application of the new reproductive technologies, and especially of oocyte donation. PMID- 8473474 TI - Mifepristone (RU 486) induces embryo expulsion in first trimester non-developing pregnancies: a prospective randomized trial. AB - This study was designed to investigate the use of oral mifepristone (RU 486) for the induction of natural expulsion of concepti in women with spontaneously interrupted pregnancy in the first trimester. It consisted of a double-blind placebo-controlled study of mifepristone (600 mg) against placebo. A total of 46 women consulting for interrupted pregnancy were diagnosed at ultrasound with no clinical sign of miscarriage. Measurements were made of the occurrence of natural expulsion, the frequency of complete expulsion, the need for subsequent surgical evacuation, analgesia and the need for transfusion. Natural expulsion occurred within 5 days in 82% of patients receiving mifepristone treatment versus 8% of placebo-treated patients (P < 0.001). All patients experienced bleeding after RU 486 and two needed emergency aspiration for haemorrhagic expulsion. The treatment failed in four patients, who underwent evacuation under local anaesthesia. In the control group, 19 patients underwent evacuation under local (n = 10) or general (n = 9) anaesthesia. It was concluded that a standard oral pilot dose of 600 mg of mifepristone induces natural expulsion in 82% of women with non-developing first trimester intrauterine pregnancies. PMID- 8473475 TI - The high fertility of agonadal and amenorrhoeic women after oocyte donation. PMID- 8473476 TI - The high fertility of agonadal and amenorrhoeic women after oocyte donation. PMID- 8473477 TI - The fraud conviction of Cecil B. Jacobson. PMID- 8473478 TI - Treatment of severe male infertility with pure follicle-stimulating hormone (FSH): the need for a properly controlled multicentre trial. PMID- 8473479 TI - The power of negative thinking. PMID- 8473480 TI - Preventing antiphospholipid antibody-induced fetal loss: a new idea. PMID- 8473481 TI - Vitamin K nutrition and postmenopausal osteoporosis. PMID- 8473482 TI - Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits. AB - The effect of the antioxidant butylated hydroxytoluene (BHT) on the accumulation of intimal smooth muscle cells (SMC) and development of intimal thickening after balloon catheter injury of the aorta were studied in rabbits with dietary-induced hyperlipidemia. Two sets of New Zealand White rabbits (eight rabbits in each group) were fed either 0.25% cholesterol or 0.25% cholesterol/1% BHT for a total of 6 wk. Serum lipid levels did not differ between the two groups. 3 wk after the start of the study, a balloon injury of the aorta was performed, after which the rabbits were kept on their respective diets for another 3 wk. After this period of time, the rabbits were killed and their aortas were investigated. The BHT treated rabbits had only one fourth of the intimal thickness (P < 0.0001) and half the number of SMC/mm intima (P < 0.001), as compared to the rabbits fed only cholesterol. There was also a lower number of macrophages in the BHT-treated group. T lymphocytes were present in the intima of cholesterol-fed rabbits, whereas no such cells could be identified in the BHT-fed animals. There were significantly lower levels of autooxidation products of cholesterol (7 oxocholesterol, cholesterol-5,6-epoxide, and 7 beta-hydroxycholesterol) in the aortas of BHT-treated rabbits, P < 0.001. In conclusion, the antioxidant BHT effectively inhibited the accumulation of intimal SMC and the development of intimal thickening of the aorta in hypercholesterolemic rabbits after a balloon catheter-induced injury. These results indicate that antioxidants may modify intimal response to injury. PMID- 8473483 TI - Replication of Marburg virus in human endothelial cells. A possible mechanism for the development of viral hemorrhagic disease. AB - Marburg and Ebola virus, members of the family Filoviridae, cause a severe hemorrhagic disease in humans and primates. The disease is characterized as a pantropic virus infection often resulting in a fulminating shock associated with hemorrhage, and death. All known histological and pathophysiological parameters of the disease are not sufficient to explain the devastating symptoms. Previous studies suggested a nonspecific destruction of the endothelium as a possible mechanism. Concerning the important regulatory functions of the endothelium (blood pressure, anti-thrombogenicity, homeostasis), we examined Marburg virus replication in primary cultures of human endothelial cells and organ cultures of human umbilical cord veins. We show here that Marburg virus replicates in endothelial cells almost as well as in monkey kidney cells commonly used for virus propagation. Our data support the concept that the destruction of endothelial cells resulting from Marburg virus replication is a possible mechanism responsible for the hemorrhagic disease and the shock syndrome typical of this infection. PMID- 8473484 TI - Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. AB - The effect of human eosinophil major basic protein (MBP) as well as other eosinophil proteins, on binding of [3H]N-methyl-scopolamine ([3H]NMS: 1 x 10(-10) M) to muscarinic M2 receptors in heart membranes and M3 receptors in submandibular gland membranes was studied. MBP inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors. MBP also inhibited atropine induced dissociation of [3H]NMS-receptor complexes in a dose-dependent fashion, demonstrating that the interaction of MBP with the M2 muscarinic receptor is allosteric. This effect of MBP suggests that it may function as an endogenous allosteric inhibitor of agonist binding to the M2 muscarinic receptor. Inhibition of [3H]NMS binding by MBP was reversible by treatment with heparin, which binds and neutralizes MBP. Eosinophil peroxidase (EPO) also inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors and inhibited atropine-induced dissociation of [3H]NMS-receptor complexes. On a molar basis, EPO is less potent than MBP. Neither eosinophil cationic protein nor eosinophil-derived neurotoxin affected binding of [3H]NMS to M2 receptors. Thus both MBP and EPO are selective allosteric antagonists at M2 receptors. The effects of these proteins may be important causes of M2 receptor dysfunction and enhanced vagally mediated bronchoconstriction in asthma. PMID- 8473485 TI - Induction patterns of 70 genes during nine days after hepatectomy define the temporal course of liver regeneration. AB - Liver regeneration is an important process that allows for recovery from hepatic injuries caused by viruses, toxins, ischemia, surgery, and transplantation. Previously, we identified > 70 immediate-early genes induced in regenerating liver after hepatectomy, 41 of which were novel. While it is expected that the proteins encoded by these genes may have important roles in regulating progression through the G1 phase of the cell cycle during regeneration, we were surprised to note that many of these "early" genes are expressed for extended periods during the hepatic growth response. Here we define several patterns of expression of immediate-early, delayed-early, and liver-specific genes during the 9-d period after hepatectomy. One pattern of induction parallels the major growth period of the liver that ends at 60-72 h after hepatectomy. A second pattern has two peaks coincident with the first and second G1 phases of the two hepatic cell cycles. A third group, which includes liver-specific genes such as C/EBP alpha, shows maximal expression after the growth period. Although the peak in DNA synthesis in nonparenchymal cells occur 24 h later than in hepatocytes, most of the genes studied demonstrate similar induction in both cell types. This finding suggests that the G0/G1 transition occurs simultaneously in all cells in the liver, but that the G1 phase of nonparenchymal cells may be relatively prolonged. Finally, we examined the expression of > 70 genes in clinical settings that could induce liver regeneration, including after perfusion in a donor liver, hepatic ischemia, and fulminant hepatic failure. We found that a small number of early and liver-specific genes were selectively activated in human livers under these conditions, and we thereby provide a potential means of measuring the caliber of the regenerative response in clinical situations. PMID- 8473486 TI - Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver. AB - This study was designed to investigate the mechanism for ethanol-induced hepatic vasoconstriction in isolated perfused rat liver. Upon initiation of ethanol infusion into the portal vein at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phenomenon). Endothelin-1 antiserum significantly inhibited this ethanol-induced hepatic vasoconstriction by 45-80%. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, after the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phenomenon and sustained the vasoconstriction. This study supports the hypothesis that two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide, regulate hepatic vascular tone in the presence of ethanol. PMID- 8473487 TI - Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. AB - Plasma and whole-body turnover studies of human C-reactive protein (CRP), isolated from a single normal healthy donor and labeled with 125I, were undertaken in 8 healthy control subjects and 35 hospitalized patients including cases of rheumatoid arthritis, systemic lupus erythematosus, infections, and neoplasia. Plasma clearance of 125I-CRP closely approximated to a monoexponential function and was similar in the control and all patient groups. There was no evidence for accelerated clearance or catabolism of CRP in any of the diseases studied. The 19-h half-life was more rapid than that of most human plasma proteins studied previously, and the fractional catabolic rate was independent of the plasma CRP concentration. The synthesis rate of CRP is thus the only significant determinant of its plasma level, confirming the validity of serum CRP measurement as an objective index of disease activity in disorders associated with an acute-phase response. Approximately 90% of injected radioactivity was recovered in the urine after 7 d, and scintigraphic imaging studies with 123I labeled CRP in 10 patients with different focal pathology showed no significant localization of tracer. The functions of CRP are thus likely to be effected predominantly in the fluid phase rather than by major deposition at sites of tissue damage or inflammation. PMID- 8473488 TI - Vasodilator and constrictor actions of platelet-activating factor in the isolated microperfused afferent arteriole of the rabbit kidney. Role of endothelium derived relaxing factor/nitric oxide and cyclooxygenase products. AB - It has been suggested that platelet-activating factor (PAF) plays a prominent role in the control of glomerular hemodynamics in various physiological and pathological conditions. We examined the direct effect of PAF on rabbit glomerular afferent arterioles (Af-Arts) microperfused in vitro and tested whether endothelium-derived relaxing factor/nitric oxide (EDNO) and cyclooxygenase products are involved in its actions. In nanomolar concentrations PAF caused dose-dependent constriction of Af-Arts, with the maximum constriction being 34 +/- 10% at 4 x 10(-8) M (n = 9, P < 0.001). The constriction was blunted by cyclooxygenase inhibition (11 +/- 6%, n = 7, P < 0.05) but augmented by EDNO inhibition (76 +/- 14%, n = 8, P < 0.005). To study a possible vasodilator effect of PAF, Af-Arts were preconstricted with norepinephrine and increasing concentrations of PAF added to the lumen. At picomolar concentrations (lower than those that caused constriction), PAF produced dose-dependent vasodilation that was unaffected by cyclooxygenase inhibition but was abolished by EDNO synthesis inhibition. Both PAF-induced constriction and dilation of Af-Arts were blocked by a PAF receptor antagonist. This study demonstrates that PAF has a receptor mediated biphasic effect on rabbit Af-Arts, dilating them at low concentrations while constricting them at higher concentrations. Our results suggest that PAF's vasodilator action may be due to production of EDNO, while its constrictor action is mediated at least in part through cyclooxygenase products. PMID- 8473489 TI - N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes. AB - When rat hepatocytes were incubated with albumin complexed to the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), rather than to oleic acid (OA), the secretion of newly synthesized apoprotein B100 (apoB100) or B48 (apoB48) was reduced, despite stimulation of cellular triglyceride synthesis by all three fatty acids. When pulse-chase studies of apoB synthesis and secretion were performed in the presence of OA, EPA, or DHA, there were no significant changes in the initial synthetic rates of either apoB species. However, during the chase period, the total recovery of labeled apoB100 and apoB48 from the cell and medium was less in the n-3 fatty acid groups, so that by 150 min, approximately half as much labeled apoB was recovered as in the OA group. Overall, the decreased accumulation in medium of labeled apoB in the presence of EPA and DHA could be quantitatively accounted for by increased degradation of intracellular apoB. Thus, in the primary hepatocyte, apoB degradation is not constitutive, but can be regulated by n-3 fatty acids. PMID- 8473490 TI - Cytokine patterns in the pathogenesis of human leishmaniasis. AB - The host response to infection appears to be regulated by specific patterns of local cytokine production. In the mouse, resistance to many pathogens including Leishmania is associated with a TH1 cytokine profile, IL-2 and IFN-gamma; whereas susceptibility to infection is associated with production of TH2 cytokines, IL-4, IL-5, and IL-10. To determine the cytokine patterns of the local immune response to Leishmania infection in humans, we used the polymerase chain reaction to compare cytokine mRNAs in biopsy specimens of American cutaneous leishmaniasis. In localized cutaneous leishmaniasis and the Montenegro delayed-type hypersensitivity reaction, type 1 cytokine mRNAs such as IL-2, IFN-gamma, and lymphotoxin were relatively predominant. In the chronic and destructive mucocutaneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL-4 mRNA in lesions. These results suggest that clinical course of infection with Leishmania braziliensis in man is associated with specific local patterns of cytokine production. PMID- 8473491 TI - Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis. AB - We have identified a novel autoantibody reactive with all three classes of RNA polymerases, well-characterized nuclear enzymes, in sera from patients with systemic sclerosis (SSc). After incubation with [35S]methionine-labeled HeLa cell extracts, 14 of 275 SSc sera immunoprecipitated 12 or 14 proteins with similar molecular weights as those of several subunit proteins of eukaryotic RNA polymerases I, II, and III. Purified IgG from these two types of sera inhibited RNA transcription catalyzed by RNA polymerases I, II, and III in vitro. Immunoblot analysis using RNA polymerase-enriched fraction showed that the majority of these sera reacted with 42- or 25-kD protein. Anti-RNA polymerase antibody was highly specific to SSc, especially to diffuse cutaneous SSc. Clinical features associated with this antibody included a high frequency of heart and kidney involvement and a poor survival rate at 5 yr after first visit. These findings indicate that the autoantibody to three classes of RNA polymerases is a new marker for a unique subset of diffuse cutaneous SSc. PMID- 8473492 TI - Homologous upregulation of human arterial alpha-adrenergic responses by guanadrel. AB - The purpose of this study was to test the hypothesis that there is homologous upregulation of arterial alpha-adrenergic responsiveness during suppression of sympathetic nervous system (SNS) activity in humans. 10 subjects (19-28 yr) were studied during placebo and when SNS activity was suppressed by guanadrel. Changes in forearm blood flow (FABF) mediated by the intraarterial infusion of norepinephrine (NE), angiotensin II (AII), and phentolamine were measured by plethysmography. During guanadrel compared with placebo, plasma NE levels (1.28 +/- 0.09-0.85 +/- 0.06 nM; P = 0.0001) and the extra vascular NE release rate derived from [3H]NE kinetics were lower (7.1 +/- 0.7-4.0 +/- 0.2 nmol/min per m2; P = 0.0004), suggesting suppression of SNS activity. During guanadrel, there was increased sensitivity in the FABF response to NE (analysis of variance P = 0.03). In contrast, there was no difference in the FABF response to AII (analysis of variance P = 0.81), suggesting that the upregulation observed to NE was homologous. The increase in FABF during phentolamine was similar during guanadrel compared with placebo (guanadrel: 141 +/- 37 vs. placebo; 187 +/- 27% increase; P = 0.33), suggesting that there was at least partial compensation to maintain constant endogenous arterial alpha-adrenergic tone. We conclude that there is homologous upregulation of arterial alpha-adrenergic responsiveness in humans when SNS activity is suppressed by guanadrel. PMID- 8473493 TI - In vivo metabolism of a mutant form of apolipoprotein A-I, apo A-IMilano, associated with familial hypoalphalipoproteinemia. AB - Apo A-IMilano is a mutant form of apo A-I in which cysteine is substituted for arginine at amino acid 173. Subjects with apo A-IMilano are characterized by having low levels of plasma HDL cholesterol and apo A-I. To determine the kinetic etiology of the decreased plasma levels of the apo A-I in these individuals, normal and mutant apo A-I were isolated, radiolabeled with either 125I or 131I, and both types of apo A-I were simultaneously injected into two normal control subjects and two subjects heterozygous for apo A-IMilano. In the normal subjects, apo A-IMilano was catabolized more rapidly than the normal apo A-I (mean residence times of 5.11 d for normal apo A-I vs. 3.91 d for apo A-IMilano), clearly establishing that apo A-IMilano is kinetically abnormal and that it has a shortened residence time in plasma. In the two apo A-IMilano subjects, both types of apo A-I were catabolized more rapidly than normal (residence times ranging from 2.63 to 3.70 d) with normal total apo A-I production rates (mean of 10.3 vs. 10.4 mg/kg per d in the normal subjects). Therefore, in the subjects with apo A IMilano, the decreased apo A-I levels are caused by rapid catabolism of apo A-I and not to a decreased production rate, and the abnormal apo A-IMilano leads to the rapid catabolism of both the normal and mutant forms of apo A-I in the affected subjects. PMID- 8473494 TI - Differential effects of renin-angiotensin system blockade on atherogenesis in cholesterol-fed rabbits. AB - To investigate the mechanism by which angiotensin-converting enzyme (ACE) inhibition attenuates atherogenesis, we have studied the effects of a non sulfhydryl ACE inhibitor, enalapril, and an angiotensin receptor antagonist, SC 51316, in cholesterol-fed rabbits. After 3 mo of enalapril treatment (10 mg/kg per d, p.o.) the percent plaque areas in the thoracic aortas of treated animals were significantly reduced (controls: 86.8 +/- 3.5%; treated: 31.1 +/- 8%, P < 0.001). Aortic cholesterol content was also reduced (controls: 31.4 +/- 3.2 mg/g tissue; treated: 7.4 +/- 1.8 mg/g, P < 0.001). Enalapril had no significant effect on plasma lipid levels or conscious blood pressure. In a second study, the angiotensin II receptor antagonist SC-51316 was administered at a dose equivalent to enalapril at blocking angiotensin pressor effects in vivo (30 mg/kg per d, p.o.). Evaluation after 3 mo indicated no significant attenuation of aortic atherosclerosis. These results demonstrate that: (a) enalapril attenuates atherogenesis without affecting either blood pressure or plasma lipid levels; (b) antioxidant activity, found with sulfhydryl-containing ACE inhibitors, is not necessary for reducing plaque formation; and (c) the attenuation of atherogenesis by ACE inhibition may not be due to blockade of the renin-angiotensin system. Alternatively, one must consider the multiple effects of ACE inhibition on other hormone systems, such as bradykinin, or the possibility that alternate angiotensin II receptors may be involved in atherosclerosis. PMID- 8473495 TI - Negative transcriptional regulation of human interleukin 2 (IL-2) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT. AB - IL-2 gene transcription is affected by several nuclear proteins. We asked whether dexamethasone (Dex) and cyclosporin A (CsA) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter. Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays. Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT, but not of NF-kB and OCT-1/OAF, to their corresponding sites on the IL-2 gene promoter. To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression, we used transient DNA transfections. Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1, NF-AT, and NF-kB motifs. Dex inhibited the IL-2 promoter and the AP-1, but not the NF-AT and NF-kB plasmids. In contrast, CsA inhibited the IL-2 promoter and the NF-AT, but not the AP-1 and NF-kB plasmids. These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF AT. We propose that, while maximum inhibition may involve interaction with both transcription factors, AP-1 is the primary target of Dex. PMID- 8473496 TI - Dual Ca2+ requirement for optimal lipid peroxidation of low density lipoprotein by activated human monocytes. AB - The oxidative modification of LDL seems a key event in atherogenesis and may participate in inflammatory tissue injury. Our previous studies suggested that the process of LDL oxidation by activated human monocytes/macrophages required O2 and activity of intracellular lipoxygenase. Herein, we studied the mechanisms involved in this oxidative modification of LDL. In this study, we used the human monocytoid cell line U937 to examine the role of Ca2+ in U937 cell-mediated lipid peroxidation of LDL. U937 cells were activated by opsonized zymosan. Removal of Ca2+ from cell culture medium by EGTA inhibited U937 cell-mediated peroxidation of LDL lipids. Therefore, Ca2+ influx and mobilization were examined for their influence on U937 cell-mediated LDL lipid peroxidation. Ca2+ channel blockers nifedipine and verapamil blocked both Ca2+ influx and LDL lipid peroxidation by activated U937 cells. The inhibitory effects of nifedipine and verapamil were dose dependent. TMB-8 and ryanodine, agents known to prevent Ca2+ release from intracellular stores, also caused a dose-dependent inhibition of LDL lipid peroxidation by activated U937 cells while exhibiting no effect on Ca2+ influx. Thus, both Ca2+ influx through functional calcium channels and Ca2+ mobilization from intracellular stores participate in the oxidative modification of LDL by activated U937 cells. 45Ca2+ uptake experiments revealed profound Ca2+ influx during the early stages of U937 cell activation, however, the Ca2+ ionophore 4 bromo A23187 was unable to induce activation of U937 cells and peroxidation of LDL lipids. Release of intracellular Ca2+ by thapsigargin only caused a suboptimal peroxidation of LDL lipids. Our results indicate that although increases in intracellular Ca2+ levels provided by both influx and intracellular Ca2+ mobilization are required, other intracellular signals may be involved for optimal peroxidation of LDL lipids by activated human monocytes. PMID- 8473497 TI - Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit. AB - Angiotensin II (Ang II) resets the baroreflex control of heart rate to a higher blood pressure. This action is apparently mediated via Ang II receptors in the area postrema, but it is not known if these are of the AT1 or AT2 subtype. In the present study the effects of losartan, a selective AT1 receptor antagonist, and PD 123319, a selective AT2 antagonist, on the cardiac baroreflex response to Ang II were investigated in conscious rabbits with chronically implanted arterial and venous catheters. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside (2.6-25 micrograms/kg per min) and analyzed using a four-parameter logistic model to yield their upper and lower plateaus, arterial pressure at the midpoint of the heart rate range (BP50), and slope coefficient. From these four parameters, the gain and range of the baroreflex were calculated. Background intravenous infusion of Ang II at 10 ng/kg per min increased mean arterial pressure by 17 mmHg but did not change heart rate. Ang II shifted the baroreflex curve to the right as indicated by an increase in BP50 from 70.9 +/- 2.0 to 89.3 +/- 2.7 mmHg (P < 0.05), but did not change baroreflex gain significantly. Ang II did not alter the upper plateau of the baroreflex, but decreased the lower plateau from 119.4 +/- 10.3 to 73.6 +/- 11.5 beats per minute (bpm) (P < 0.05), extending the heart rate range by 52.5 bpm. Pretreatment with losartan completely abolished the pressor and cardiac baroreflex responses to Ang II. In contrast, PD 123319 had no effect on these responses. Administration of losartan alone to block endogenous Ang II shifted the baroreflex curve to the left as indicated by a decrease in BP50 from 71.2 +/- 2.7 to 64.7 +/- 2.5 mmHg (P < 0.05). These results demonstrate that the resetting of the baroreflex control of heart rate by Ang II is mediated by AT1 receptors, and that basal levels of endogenous Ang II exert a tonic action on the cardiac baroreflex to increase the setpoint around which the baroreflex regulates heart rate. PMID- 8473498 TI - Cloning of a virulence factor of Entamoeba histolytica. Pathogenic strains possess a unique cysteine proteinase gene. AB - Cysteine proteinases are hypothesized to be important virulence factors of Entamoeba histolytica, the causative agent of amebic dysentery and liver abscesses. The release of a histolytic cysteine proteinase from E. histolytica correlates with the pathogenicity of both axenic strains and recent clinical isolates as determined by clinical history of invasive disease, zymodeme analysis, and cytopathic effect. We now show that pathogenic isolates have a unique cysteine proteinase gene (ACP1). Two other cysteine proteinase genes (ACP2, ACP3) are 85% identical to each other and are present in both pathogenic and nonpathogenic isolates. ACP1 is only 35 and 45% identical in sequence to the two genes found in all isolates and is present on a distinct chromosome-size DNA fragment. Presence of the ACP1 gene correlates with increased proteinase expression and activity in pathogenic isolates as well as cytopathic effect on a fibroblast monolayer, an in vitro assay of virulence. Analysis of the predicted amino acid sequence of the ACP1 proteinase gene reveals homology with cysteine proteinases released by activated macrophages and invasive cancer cells, suggesting an evolutionarily conserved mechanism of tissue invasion. The observation that a histolytic cysteine proteinase gene is present only in pathogenic isolates of E. histolytica suggests that this aspect of virulence in amebiasis is genetically predetermined. PMID- 8473499 TI - Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans. AB - Lymphocytes, especially CD4+ T cells, are essential for clearance of the yeast like organism Cryptococcus neoformans from the infected host. The mechanism(s) by which the lymphocytes facilitate elimination of cryptococci has not been elucidated. It is generally thought, however, that lymphocytes reactive with C. neoformans indirectly function by production of lymphokines to enhance clearance of the organism by natural effector cells such as macrophages. In the present study, we assessed the ability of freshly isolated human lymphocytes to interact directly with C. neoformans and to limit the growth of the organism in vitro. We found that large granular lymphocytes (LGL) as well as T cells bound to cryptococcal cells when the lymphocytes were mixed with the cryptococcal cells at a 2:1 ratio. The physical binding interactions of the two lymphocyte populations were different. LGL attached to the cryptococcal cells by many microvilli; T lymphocytes associated with the yeast through broad areas of membrane attached to the cryptococcal cell surface. The two types of lymphocyte interactions did not result in phagocytosis but resulted in direct inhibition of cryptococcal growth, making these lymphocyte interactions with cryptococci distinctly different from interactions of monocytes with cryptococci. With the human natural killer (NK) cell line, NK 3.3, we confirmed that NK cells that were present in the LGL population were capable of limiting the growth of C. neoformans. Through immunoelectron microscopy, human CD3+ lymphocytes were seen attached to cryptococcal cells and by mass cytolysis, human CD3+ lymphocytes were shown to be responsible for inhibition of C. neoformans growth. The direct inhibitory interactions of NK cells and T lymphocytes with cryptococcal cells may be important means of host defense against this ubiquitous organism that frequently causes life-threatening disease in AIDS patients. PMID- 8473500 TI - Induction of cytokine expression by leukemia inhibitory factor. AB - Biological effects of cytokines are in part determined by their interactions in the regulation of cytokine production. This study analyzes the effects of leukemia inhibitory factor (LIF) on cytokine expression in different cell lineages. Recombinant human LIF increases levels of IL-1 beta, IL-6, and IL-8 mRNA in human articular chondrocytes as demonstrated by Northern blotting. These cytokine mRNAs are detectable as early as 1.3 h after stimulation and reach their maximum after 5 h. The LIF effects are dose dependent and of similar magnitude to those of IL-1. By metabolic labeling and immunoprecipitation it is shown that LIF induces synthesis and secretion of IL-6. IL-6 bioactivity in conditioned media, as measured by the B9 hybridoma proliferation assay, is increased by LIF. Effects of LIF on cytokine expression are not confined to connective tissue cells. By PCR it is shown that human blood monocytes express IL-6 mRNA after stimulation with LIF. An increase in IL-6 mRNA levels is detectable 2 h after stimulation, and this starts to decline by 5 h. The response is of shorter duration as compared with IL-1 beta. In addition to increased mRNA expression, LIF also stimulates release of biologically active IL-6 from blood monocytes. In synoviocytes and neuronal as well as epithelial cell lines, LIF increases IL-1 beta and IL-6 gene expression. In summary, LIF induces cytokine expression in a wide variety of tissues. These results suggest that through the induction of cytokines, LIF can modulate inflammation, immune responses, and connective tissue metabolism, and act as a pathogenetic mediator in different disease states. PMID- 8473501 TI - NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties. AB - Recent evidence suggests that sulfhydryl species can react with oxides of nitrogen under physiologic conditions and thereby stabilize endothelium-derived relaxing factor (EDRF) activity, but the presence of a specific in vivo thiol carrier for nitric oxide (NO) remains controversial. The single free sulfhydryl of serum albumin is the most abundant thiol species in plasma (approximately 0.5 mM) and is particularly reactive towards NO. To examine the potential role of serum albumin in endogenous nitric oxide metabolism, we synthesized S-nitroso-BSA (S-NO-BSA), a model S-nitroso-protein, and examined its effects on platelet function and coronary and systemic vascular tone in 16 mongrel dogs. Intravenous bolus S-NO-BSA markedly reduced mean arterial pressure in a dose-dependent manner and proved seven and a half-fold less potent than intravenous nitroglycerin and 10-fold less potent than intravenous S-nitroso-cysteine (half-maximal response of 75 nmol/kg compared to 10 and 7.5 nmol/kg, respectively; P < 0.05); when given by intravenous infusion (half-maximal response = 10 nmol/kg per min), however, S-NO BSA and nitroglycerin were equipotent. Intravenous bolus S-NO-BSA had a greater duration of action than either nitroglycerin or S-nitroso-cysteine and produced marked prolongation of the template bleeding time associated with dose-dependent inhibition of ex vivo platelet aggregation (half-maximal response approximately 70 nmol/kg). Intracoronary S-NO-BSA increased coronary blood flow (mean +/- SEM) less effectively than nitroprusside, acetylcholine, or S-nitroso-cysteine (165% +/- 24% vs. 315% +/- 82%, 483% +/- 55%, or 475% +/- 66%, respectively; P < 0.05) although with much longer duration of action. On a molar basis, S-nitroso cysteine proved more effective than S-nitroso-BSA, nitroprusside, or acetylcholine as an epicardial coronary vasodilator. Thus, serum albumin reacts with oxides of nitrogen to form a stable S-nitroso-thiol with properties reminiscent of authentic EDRF supporting the view that protein associated thiol may participate in the action and metabolism of EDRF. PMID- 8473502 TI - Fluid and electrolyte transport by cultured human airway epithelia. AB - An understanding of the fluid and electrolyte transport properties of any epithelium requires knowledge of the direction, rate, and regulation of fluid transport and the composition of the fluid. Although human airway epithelial likely play a key role in controlling the quantity and composition of the respiratory tract fluid, evidence for such a role is not available. To obtain such knowledge, we measured fluid and electrolyte transport by cultured human nasal epithelia. Under basal conditions we found that epithelia absorbed Na+ and fluid; both processes were inhibited by addition of amiloride to the mucosal surface. These data suggest that active Na+ absorption is responsible for fluid absorption. Interestingly, Na+ absorption was not accompanied by the net absorption of Cl-; some other anion accompanied Na+. The combination of cAMP agonists and mucosal amiloride stimulated the secretion of NaCl-rich fluid. But surprisingly, the response to cAMP agonists in the absence of amiloride showed substantial intersubject variability: cAMP stimulated fluid secretion across some epithelia, for others, cAMP stimulated fluid absorption. The explanation for the differences in response is uncertain, but we speculate that the magnitude of apical membrane Na+ conductance may modulate the direction of fluid transport in response to cAMP. We also found that airway epithelial secrete H+ and absorb K+ under basal conditions; both processes were inhibited by cAMP agonists. Because the H+/K(+)-ATPase inhibitor, SCH 28080, inhibited K+ absorption, an apical membrane H+/K(+)-ATPase may be at least partly responsible for K+ and H+ transport. However, H+/K+ exchange could not entirely account for the luminal acidification. The finding that cAMP agonists inhibited luminal acidification may be explained by the recent finding that cAMP increases apical HCO3- conductance. These results provide new insights into how the intact airway epithelium may modify the composition of the respiratory tract fluid. PMID- 8473503 TI - Diaphragm mechanics in dogs with unilateral emphysema. AB - We studied dogs with unilateral papain-induced emphysema to answer two questions: (1) Do emphysema lung-apposed hemidiaphragm (DiE) and normal lung-apposed hemidiaphragm (DiN) have equal capacities for lowering lung surface pressure? and (2) Are side-to-side differences in intrathoracic pressure the result of unequal force outputs by DiE and DiN or are they caused by differences in their mechanical efficiency as pressure generators? After the airways of the emphysematous and normal lungs were intubated with a dual lumen endotracheal tube, both phrenic nerves were maximally stimulated at rates between 1 and 50 Hz and the changes in airway occlusion pressure (delta PaoE,N) and diaphragm length (sonomicrometry) were recorded. In all animals, delta PaoN exceeded delta PaoE. Differences in pressure ranged from 1.2 +/- 0.6 cm H2O during a twitch to 6.0 +/- 2.9 cm H2O during a 50-Hz tetanus. Midcostal bundles of DiE shortened less than corresponding bundles of DiN, but both reached the same active length relative to their optimal lengths, which were measured in vitro. There was no significant difference in fiber type distribution, fiber cross-sectional area, or maximal isometric tetanic tensions among midcostal regions of DiE and DiN. We conclude that unilateral hyperinflation impairs the mechanical efficiency of the apposing hemidiaphragm as a pressure generator. PMID- 8473504 TI - Medium tonicity regulates expression of the Na(+)- and Cl(-)-dependent betaine transporter in Madin-Darby canine kidney cells by increasing transcription of the transporter gene. AB - Betaine is one of the major compatible osmolytes accumulated by kidney derived Madin-Darby canine kidney cells cultured in hypertonic medium. Betaine is accumulated by Na(+)- and Cl(-)-dependent uptake from the medium. To gain insight into the mechanism by which hypertonicity evokes an increase in the Vmax of the betaine transporter in Madin-Darby canine kidney cells, we measured the relative abundance of mRNA for the transporter in cells shifted to a hypertonic medium and found parallel increases in mRNA abundance and cotransporter activity. The increase in mRNA levels preceded the increase in transporter activity slightly. Transcription of the gene for the transporter rose rapidly and to the same relative extent as mRNA abundance in cells shifted to hypertonic medium, indicating that transcription of the gene for the cotransporter plays a major role in regulating the accumulation of betaine in response to hypertonicity. PMID- 8473506 TI - Sequence polymorphisms in the apolipoprotein (a) gene. Evidence for dissociation between apolipoprotein(a) size and plasma lipoprotein(a) levels. AB - Apolipoprotein(a) [apo(a)], an apolipoprotein unique to lipoprotein(a) [Lp(a)], is highly polymorphic in size. Previous studies have indicated that the size of the apo(a) gene tends to be inversely correlated with the plasma level of Lp(a). However, several exceptions to this general trend have been identified. Individuals with apo(a) alleles of identical size do not always have similar plasma concentrations of Lp(a). To determine if these differences in plasma Lp(a) concentrations were due to sequence variations in the apo(a) gene, we examined the sequences of apo(a) alleles in 23 individuals homozygous for same-sized apo(a) alleles. We identified four single-strand DNA conformation polymorphisms (SSCPs) in the apo(a) gene. Of the 23 homozygotes, 21 (91%) were heterozygous for at least one of the SSCPs. Analysis of a family in which a parent was homozygous for the same-sized apo(a) allele revealed that each allele, though identical size, segregated with different plasma concentrations of Lp(a). These studies indicate that the apo(a) gene is even more polymorphic in sequence than was previously appreciated, and that sequence variations at the apo(a) locus, other than the number of kringle 4 repeats, contribute to the plasma concentration of Lp(a). PMID- 8473505 TI - Bone marrow cells in X-linked agammaglobulinemia express pre-B-specific genes (lambda-like and V pre-B) and present immunoglobulin V-D-J gene usage strongly biased to a fetal-like repertoire. AB - Expression of Ig and Ig-related genes has been studied in bone marrow cells from two patients with severe form of X-linked agammaglobulinemia (XLA). Phenotypic analysis revealed the presence of pre-B cells, in the absence of mature B cell markers. The pre-B-specific genes, lambda-like and V pre-B, were normally transcribed. Sequence analysis of 48 distinct V-D-J cDNA clones directly derived from XLA bone marrow cells indicated that they had characteristics of an early fetal pre-B repertoire. All VH families were identified, with a strong bias in the gene usage: a few VH genes were largely overexpressed, either germline or slightly mutated; most genes had been located 3' of the VH locus and were also used in fetal liver (8-13 wk of gestation). Short D regions, (resulting from D-D fusion, making usage of all D genes in both orientations with utilization of the three reading frames), restricted N diversity, and a fetal JH usage pattern were also observed. Taken together, our data suggest that the XLA defect does not alter V-D-J rearrangements nor the expression of mu, lambda-like, and V pre-B transcripts and most likely results in a poor efficiency of some critical steps of the B cell maturation. PMID- 8473507 TI - Molecular basis for fibrinogen Dusart (A alpha 554 Arg-->Cys) and its association with abnormal fibrin polymerization and thrombophilia. AB - The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C-->T) in the A alpha-chain gene, resulting in the amino acid substitution A alpha 554 Arg-->Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen-albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (A alpha 554 Arg-->Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals. PMID- 8473508 TI - Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. AB - The interstices of the mammalian stratum corneum contain lipids in a system of continuous membrane bilayers critical for the epidermal permeability barrier. During the transition from inner to outer stratum corneum, the content of polar lipids including glucosylceramides, decreases while ceramide content increases. We investigated whether inhibition of glucosylceramide hydrolysis would alter epidermal permeability barrier function. Daily topical applications of bromoconduritol B epoxide (BrCBE) to intact murine skin selectively inhibited beta-glucocerebrosidase, increased glucosylceramide content of stratum corneum with ceramide content remaining largely unchanged, and caused a progressive, reversible decrease in barrier function. Histochemistry of inhibitor-treated epidermis revealed persistence of periodic acid-Schiff-positive staining in stratum corneum cell membranes, consistent with retention of hexose moieties. Electron microscopy of inhibitor-treated samples revealed no evidence of toxicity or changes in the epidermal lipid delivery system. However, immature membrane structures persisted in the intercellular spaces throughout the stratum corneum, with reappearance of mature membrane structures progressing outward from the lower stratum corneum upon termination of BrCBE. Finally, the induced barrier abnormality was not reversed by coapplications of ceramide. These data demonstrate that glucosylceramide hydrolysis is important in the formation of the epidermal permeability barrier, and suggest that accumulation of glucosylceramides in stratum corneum intercellular membrane domains leads to abnormal barrier function. PMID- 8473509 TI - Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice. AB - In humans, diets high in saturated fat and cholesterol raise HDL-cholesterol (HDL C) levels. To explore the mechanism, we have devised a mouse model that mimics the human situation. In this model, HuAITg and control mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal) high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets. The mice responded to increased dietary fat by increasing both HDL-C and apo A-I levels, with a greater increase in HDL-C levels. This was compatible with an increase in HDL size observed by nondenaturing gradient gel electrophoresis. Turnover studies with doubly labeled HDL showed that dietary fat both increase the transport rate (TR) and decreased the fractional catabolic rate of HDL cholesterol ester (CE) and apo A-I, with the largest effect on HDL CE TR. The latter suggested that dietary fat increases reverse cholesterol transport through the HDL pathway, perhaps as an adaptation to the metabolic load of a high fat diet. The increase in apo A-I TR by dietary fat was confirmed by experiments showing increased apo A I secretion from primary hepatocytes isolated from animals on the high fat diet. The increased apo A-I production was not associated with any increase in hepatic or intestinal apo A-I mRNA, suggesting that the mechanism of the dietary fat effect was posttranscriptional, involving either increased translatability of the apo A-I mRNA or less intracellular apo A-I degradation. The dietary fat-induced decrease in HDL CE and apo A-I fractional catabolic rate may have been caused by the increase in HDL particle size, as was suggested by our previous studies in humans. In summary, a mouse model has been developed and experiments performed to better understand the paradoxical HDL-raising effect of a high fat diet. PMID- 8473510 TI - Erythrocyte membrane proteins reactive with human (warm-reacting) anti-red cell autoantibodies. AB - Immunoglobulin G (IgG) autoantibodies of 20 patients with autoimmune hemolytic anemia (AHA) were used in immunoaffinity assays with surface-radioiodinated human red blood cells (RBCs), and detergent-solubilized products were analyzed by SDS PAGE/autoradiography. Four membrane proteins were identified as candidate autoantigens: a nonglycosylated polypeptide with an apparent molecular mass of 34 kD (p34) that was expressed in all available RBC phenotypes except Rhnull but differed consistently in apparent molecular mass from the 32-kD Rh(D) polypeptide co-isolated by IgG allo-anti-D; a heterogenous 37-55-kD glycoprotein, also deficient in Rhnull RBCs, which disappeared after deglycosylation by N-glycanase, with the appearance of a sharp, new approximately 31-kD band distinct from p34 and from Rh(D) polypeptide; a approximately 100-kD major membrane glycoprotein identified by immunoblotting as the band 3 anion transporter; and glycophorin A (GPA), also confirmed by immunoblotting. GP37-55 was not seen in the absence of p34, and both proteins are likely to be members of the Rh family. Indeed, a 34-kD polypeptide band and 37-55-kD poly-disperse "smear," isolated concurrently from the same labeled RBCs by IgG allo-anti-e, were indistinguishable from their autoantibody-isolated counterparts and may well be the same protein identified at different epitopes by the auto- and allo-antibodies. Individual AHA patients' autoantibodies isolated p34 and gp37-55, alone or in combination with band 3 (nine cases); strong band 3 alone (five cases); and combinations of band 3 with GPA (six cases). The autoantibodies of three additional patients whose AHA had been induced by alpha-methyldopa also isolated p34 and gp37-55. PMID- 8473511 TI - Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression. AB - The fourth component of the human complement system (C4) is coded for by two genes, C4A and C4B, located within the MHC. Null alleles of C4 (C4Q0) are defined by the absence of C4 protein in plasma. These null alleles are due either to large gene deletions or to nonexpression of the respective genes. In a previous study, evidence was obtained for nonexpressed defective genes at the C4A locus, and for gene conversion at the C4B locus. To further characterize the molecular basis of these non-expressed C4A genes, we selected nine pairs of PCR primers from flanking genomic intron sequences to amplify all 41 exons from individuals with a defective C4A gene. The amplified products were subjected to single stranded conformation polymorphism (SSCP) analysis to detect possible mutations. PCR products exhibiting a variation in the SSCP pattern were sequenced directly. In 10 of 12 individuals studied, we detected a 2-bp insertion in exon 29 leading to nonexpression due to the creation of a termination codon, which was observed in linkage to the haplotype HLA-B60-DR6 in seven cases. In one of the other two individuals without this mutation, evidence was obtained for gene conversion to the C4B isotype. The genetic basis of C4A nonexpression in the second individual is not yet known and will be subject to further analysis. PMID- 8473512 TI - Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. AB - Autoantibodies reacting with chromatin and its components, histones and DNA, are characteristic of the human autoimmune disease SLE and drug-induced lupus, but the mechanisms of their induction remain unknown. Serial serum samples collected over short intervals from lupus-prone MRL/MP-lpr/lpr and BXSB mice were tested by ELISA on chromatin and its substructures to characterize the initial autoimmune response to these antigens. Direct binding studies demonstrated that the early autoantibodies recognized discontinuous epitopes on native chromatin and the (H2A H2B)-DNA subnucleosome. As the immune response progressed, native DNA and other chromatin constituents generally became antigenic. Based on adsorption studies and IgG subclass restriction, antibodies to native DNA were more related to chromatin than to denatured DNA. The kinetics of autoantibody appearance and the Ig class distribution were similar to the kinetics and distribution seen in antibodies induced by immunization with an exogenous T-dependent antigen. These results are most consistent with the view that autoantibodies reacting with chromatin are generated by autoimmunization with chromatin, and antibodies to native DNA are a subset of the wide spectrum of antichromatin autoantibodies. PMID- 8473513 TI - IL-1-induced murine osteoblast IL-6 production is mediated by the type 1 IL-1 receptor and is increased by 1,25 dihydroxyvitamin D3. AB - IL-1-induced osteoblast IL-6 production represents one possible mechanism by which IL-1 augments bone resorption. In this report, we show that the murine osteoblastic cell line (MC3T3-E1) expresses type 1 IL-1 receptors based on 125I HrIL1 alpha binding, blocked by type 1 IL-1R antibodies (35F5), and analysis of MC3T3 RNA by reverse transcription (RT)-DNA amplification and Northern analysis. MC3T3 cells do not express detectable type 2 IL-1R mRNA by RT-DNA amplification. IL-1 induces (IL-1 ED50, 0.1 pM) IL-6 production through the type 1 IL-1R as 35F5 antibodies block IL-1-stimulated IL-6 production. Vitamin D3 increases IL-1R expression dose- and metabolite-dependently, with 1,25-(OH)2D3 having the greatest potency, and also enhances IL-1's capacity to stimulate IL-6 production at low IL-1 levels. Both IL-1 and 1,25-(OH)2D3 induce type 1 IL-1R and not type 2 IL-1R upregulation based on ligand binding and RT-DNA amplification. Increased IL 1R expression requires a 5-7-h treatment and is protein/RNA synthesis dependent. These observations imply that IL-1-induced IL-6 production in osteoblasts is mediated by type 1 IL-1Rs and that increased IL-1R expression could play a role in mediating IL-1-induced skeletal responses. PMID- 8473514 TI - Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A I in subjects with low levels of high density lipoprotein cholesterol. AB - Plasma levels of HDL apo A-I are reduced in individuals with low HDL cholesterol (HDL-C) concentrations as a result of increased fractional catabolic rates (FCRs). To determine the basis for the high apo A-I FCRs, seven subjects with low HDL-C levels (31.0 +/- 4.3 mg/dl) were compared with three subjects with high HDL C levels (72.0 +/- 4.5 mg/dl). Each subject received autologous HDL that was labeled directly by the iodine-monochloride method (whole-labeled) and autologous HDL that was labeled by exchange with homologous radiolabeled apo A-I (exchange labeled). Blood was obtained for 2 wk, specific activities determined, and FCRs (d-1 +/- SD) estimated. In every subject, whether in the low or high HDL-C group, the exchange-labeled FCR was greater than the whole-labeled FCR. The exchange labeled FCR was higher in the low HDL-C group (0.339 +/- 0.043) versus the high HDL-C group (0.234 +/- 0.047; P < 0.009). The whole-labeled FCR was also greater in the low HDL-C group (0.239 +/- 0.023) versus the high HDL-C group (0.161 +/- 0.064; P < 0.02). In addition, in both low and high HDL groups ultracentrifugation resulted in more radioactivity in d > 1.210 (as percentage of total plasma counts per minute) with the exchange-labeled tracer than with the whole-labeled tracer (12.55 +/- 4.95% vs. 1.02 +/- 0.38%; P < 0.003). With both HDL tracers, more radioactivity was found in d > 1.210 in the low versus the high HDL-C groups. When apo A-I catabolism was studied by perfusing isolated rabbit kidneys with whole-labeled HDL, there was twice as much accumulation (cpm/g cortex) of HDL apo A-I isolated from subjects with low HDL-C than from subjects with high HDL-C (P < 0.0025). Finally, HDL that had been isolated from subjects with high levels of HDL-C was triglyceride enriched and exposed to partially purified lipases before perfusion through kidneys. Threefold more apo A-I from modified HDL accumulated in the cortex compared with the unmodified preparation (P < 0.007). The results of these in vivo and ex vivo studies indicate that individuals with low HDL-C levels have more loosely bound, easily exchanged apo A I and that this exchangeable apo A-I is more readily cleared by the kidney. PMID- 8473515 TI - Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. AB - The p53 gene was analyzed in tumor specimens obtained from 52 patients with various types of carcinoma of the thyroid gland by a combined molecular and immunocytochemical approach. The histologic types included 37 well-differentiated papillary and follicular carcinomas, 8 poorly differentiated, and 7 undifferentiated carcinomas. The p53 gene was shown to be unaffected in all differentiated tumors by single-strand conformation polymorphism analysis. However, in two out of eight (25%) of poorly differentiated carcinomas and five out of seven (71%) undifferentiated carcinomas, p53 mutations were identified and subsequently characterized by DNA sequencing. One undifferentiated carcinoma displayed two areas with varying degrees of differentiation. The comparative analysis of the p53 gene, in both the more and the less differentiated area of this tumor, clearly showed that the p53 mutation was confined to the latter component of the tumor specimen. These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis. PMID- 8473516 TI - Dietary induced subclinical vitamin K deficiency in normal human subjects. AB - A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation. PMID- 8473517 TI - Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. AB - It has been previously shown that the level of circulating undercarboxylated osteocalcin (ucOC) is elevated in elderly women in comparison with young, healthy, premenopausal ones. To understand the mechanism of the increase in the ucOC in the elderly and to assess its potential consequences on bone fragility, we have measured ucOC in the sera of 195 elderly institutionalized women 70-101 yr of age. In 45 women (23%) serum ucOC was above the upper limit of the normal range for young women. The level of ucOC was negatively correlated with 25OHD (r = -0.32, P < 0.001) even after excluding the effect of age, parathyroid hormone (PTH), and creatinine by partial correlation (r = -0.24, P < 0.002). During an 18 mo follow-up, 15 women sustained a hip fracture and their baseline ucOC level was higher (P < 0.01) in women who subsequently sustained hip fracture than in the nonfracture group contrasting with no significant differences for serum calcium, phosphate, alkaline phosphatase, creatinine, PTH, 250HD, and total and carboxylated OC. The risk of hip fracture was increased in women with elevated ucOC (relative ratio 5.9, 99.9% Cl 1.5-22.7, P < 0.001). During 1 yr of calcium/vitamin D2 treatment, ucOC decreased (P < 0.05), especially in those with the initially increased values (from 2.22 +/- 0.35 to 1.41 +/- 0.29 ng/ml, P <0.005) contrasting with an increase in the placebo group (P < 0.05). In conclusion, the increase in ucOC in the elderly reflects not only some degree of vitamin K deficiency but also their poor vitamin D status, suggesting that vitamin D may be important, either directly or indirectly through its effect on bone turnover, for achieving a normal gamma-carboxylation of OC. The ucOC, but not conventional calcium metabolism parameters, predicts the subsequent risk of hip fracture, suggesting that serum ucOC reflects some changes in bone matrix associated with increased fragility. PMID- 8473518 TI - Bone morphogenetic protein expression in human atherosclerotic lesions. AB - Artery wall calcification associated with atherosclerosis frequently contains fully formed bone tissue including marrow. The cellular origin is not known. In this study, bone morphogenetic protein-2a, a potent factor for osteoblastic differentiation, was found to be expressed in calcified human atherosclerotic plaque. In addition, cells cultured from the aortic wall formed calcified nodules similar to those found in bone cell cultures and expressed bone morphogenetic protein-2a with prolonged culture. The predominant cells in these nodules had immunocytochemical features characteristic of microvascular pericytes that are capable of osteoblastic differentiation. Pericyte-like cells were also found by immunohistochemistry in the intima of bovine and human aorta. These findings suggest that arterial calcification is a regulated process similar to bone formation, possibly mediated by pericyte-like cells. PMID- 8473519 TI - Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney. AB - In situ hybridization was used to map cellular patterns of gene expression for facilitative glucose transporters (GTs) 1-5 in the developing and adult rat kidney. GT3 was not detected. GT1 mRNA was present in the proximal straight tubule (PST), distal nephron and collecting duct. GT2 mRNA was localized in both proximal convoluted and PST, while GT5 mRNA was detected only in the PST. GT4 mRNA and immunoreactivity were focally localized in the thick ascending limb of Henle's loop and were coexpressed with IGF-I. Thus, each of the four different isoforms demonstrated a distinct renal distribution, with GTs 1, 2, and 5 coexpressed in the PST. Renal GT1 and GT5 gene expression were unchanged throughout development, while GT2 was most abundant before weaning and GT4 was first detected after weaning. Only GT4 appeared to be hormonally regulated: It was decreased after hypophysectomy and increased after vasopressin treatment, but was not affected by 1 or 4 d of insulinopenic diabetes mellitus. The coexpression of GT4 and IGF-I in the thick ascending limb segment of the nephron suggests a novel autocrine/paracrine mechanism by which cells may control local fuel economy independently from that of the larger structure to which they belong and from the systemic hormonal milieu. PMID- 8473520 TI - Hereditary tyrosinemia type I. Self-induced correction of the fumarylacetoacetase defect. AB - Two Norwegian patients with chronic tyrosinemia type I showed > 50% residual fumarylacetoacetase activity in liver samples obtained during liver transplantation. The enzyme characteristics of both patients were comparable with those of a normal control. Immunohistochemistry on liver sections from these patients and from three other Norwegian tyrosinemia patients revealed a mosaicism of fumarylacetoacetase immunoreactivity corresponding completely or partly to some of the regenerating nodules. This appearance of enzyme protein is presumably induced by the disease process. The mechanism involved remains unclear and could be caused by a genetic alteration, regained translation of messenger RNA, or to enhanced stability of an abnormal enzyme. PMID- 8473521 TI - Recombinant platelet-derived growth factor B gene expression in porcine arteries induce intimal hyperplasia in vivo. AB - Platelet-derived growth factor (PDGF) B chain induces cell proliferation in vitro and is associated with arterial lesions that cause cardiovascular disease. However, it has been difficult to document the biological response to PDGF B gene expression in arteries in vivo. To determine the biologic effects of this growth factor in vivo, we have introduced an eukaryotic expression vector plasmid encoding recombinant PDGF B by direct gene transfer into porcine iliofemoral arteries using DNA liposome complexes. The presence of PDGF B plasmid DNA and expression of recombinant mRNA were confirmed by polymerase chain reaction analysis, and recombinant PDGF protein was demonstrated by immunohistochemistry. Intimal thickening was observed in porcine arteries 21 days following transfection with the recombinant PDGF B gene compared with arteries transduced with a control gene, E. coli beta-galactosidase. An eightfold increase in intimal to medial ratio was present in PDGF B gene transfected arteries compared with control transfected arteries (P = 0.001). This study suggests that expression of a recombinant PDGF B gene in vivo can play a role in the induction of intimal hyperplasia, which can lead to cardiovascular diseases. PMID- 8473522 TI - Suppression of food intake by apolipoprotein A-IV is mediated through the central nervous system in rats. AB - The aim of this experiment was to investigate whether the anorectic effect of apolipoprotein A-IV (apo A-IV) after lipid feeding is mediated via the central nervous system. Infusion of 0.5 micrograms of apo A-IV into the third ventricle failed to suppress food intake. Higher doses (1 micrograms or higher) of apo A-IV infused into the third ventricle inhibited food intake in a dose-dependent manner. In contrast, when apo A-I was infused into the third ventricle it had no effect on food intake. To further test the hypothesis that apo A-IV is an important factor controlling food intake, we administered goat anti-rat apo A-IV serum into the third ventricle of rats that were allowed food and water and lib. In all rats tested, this treatment resulted in enhanced food intake. In contrast, infusion of goat anti-rat apo A-IV serum failed to elicit such a response. Lastly, we determined the apo A-IV concentration in plasma and cerebrospinal fluid before and during active lipid absorption. Apo A-IV concentration in cerebrospinal fluid was about 1/20 that of plasma. Both serum and cerebrospinal fluid apo A-IV increased markedly as a result of feeding of lipid. In conclusion, we propose that apo A-IV may act centrally to control food intake. PMID- 8473523 TI - Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3. AB - Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS. PMID- 8473524 TI - Enhanced prostacyclin synthesis in endothelial cells by retrovirus-mediated transfer of prostaglandin H synthase cDNA. AB - A retroviral vector (BAG) was used to transfer human prostaglandin H synthase (PGHS-1) gene into a human endothelial cell line for enhancement of PGI2 synthesis. Cells infected with BAG containing PGHS-1 cDNA in the sense orientation relative to the retroviral promoter (PGHS(S)) expressed a 30-fold increase in mRNA but, due to a reading frame shift, did not show an increase in PGHS protein or in PGI2 synthesis, while those with PGHS-1 in reverse orientation relative to the viral promoter (PGHS(R)), produced a > 10-fold increase in PGHS mRNA over the control (169 +/- 22 vs 14.8 +/- 1.2 amol/micrograms RNA) with a concordant increase in PGHS protein (5.82 +/- 1.07 vs 0.23 +/- 0.04 ng/mg protein) and enzyme activity. Primer extension analysis of PGHS(R) revealed two transcription start sites located in the SV40 late promoter region adjacent to PGHS-1 cDNA. PGHS(R) cells produced a high basal PGI2 level which was increased by several-fold in response to stimulation by ionophore, arachidonic acid, and thrombin. Kinetic analysis revealed the PGI2 synthetic rate to be 14 ng/min-1 per million cells and t1/2 of PGI2 synthesis, 13.3 min. These findings indicate that transfer of PGHS-1 gene into vascular cells enhances PGI2 synthesis and may be a useful strategy for restoring thromboprotective property of damaged blood vessels. PMID- 8473525 TI - Prediction of the development of low birth weight preterm infants by a new neonatal medical index. AB - A new neonatal medical index (NMI) was used to predict the mental and motor development of low birth weight, preterm infants up to 3-years-old. The NMI is a summary score of only a few clinically salient items that are readily available on brief chart review. The sample consisted of 512 of 608 infants randomly assigned to the control group of the eight-site Infant Health and Development Program and on whom the complete set of developmental outcome measures was available. The developmental tests administered were the Bayley Scales at 12 and 24 months and the Stanford-Binet at 3 years. The findings indicated the NMI was predictive of later cognitive and motor development, and in infants born weighing less than 1500 g, the effects of neonatal medical complications continued to adversely influence these children's development to at least 3 years of age. In the heavier babies the developmental effects of sociodemographic factors predominated by 24 months and beyond. PMID- 8473526 TI - Cranial sonography and neurological examination at term and motor performance through 19 months of age. AB - This study examined the role of cranial sonography and neurological examination in the prediction of developmental progress during the first 19 months of life in extremely preterm infants. Forty-seven infants with mean birth weight 993 +/- 197 g and gestational age 27.9 +/- 1.9 weeks were studied. Each infant was classified as normal, suspect, or abnormal using cranial sonography and a structured neurological examination. Developmental outcome was assessed using the Infant Neurological International Battery (INFANIB) at 4, 8, and 14 months and the Rockford Infant Developmental Evaluation Skills (RIDES) at 19 months. Sonographic classification was the best predictor of outcome through 14 months, F(2.72) = 12.4, p < .001. The neurological examination predicted performance only at 4 months. No infant classified as normal on both examinations was abnormal on follow-up. Infants with suspect or abnormal neurological examinations had normal outcomes if their sonographic findings were normal. PMID- 8473527 TI - Correlates of psychological adjustment to pediatric physical disorders: a meta analytic review and comparison with existing models. AB - Thirty-eight studies of correlates of children's adjustment to physical disorders were reviewed in a meta-analysis and compared with existing models. Results indicate (1) considered collectively, disease/disability risk factors, parent/family risk factors, and child characteristics are significantly correlated with child adjustment although stressors (including socioeconomic status) are not; (2) disease/disability risk factors show significantly lower correlations than do parent/family or child characteristics; (3) child characteristics show the strongest correlation to adjustment, but these measures may be contaminated because items on some of these scales (e.g., self-concept, temperament) sometimes overlap with those on measures of total adjustment. With the exception of studies of disease severity, the number of studies meeting criteria for inclusion, with quantifiable correlates and measures of adjustment, was quite small. Inclusion of child, family/parent, social and medical risk/protective factors in future models is most appropriate, but greater emphasis needs to be placed on the child and family/parent characteristics. Greater attention also must be devoted to examining the interaction of risk/protective factors, including those that may be general and those that may be specific to a particular disability. PMID- 8473528 TI - Repeated social stress during pregnancy impairs neuromotor development of the primate infant. AB - Neuromotor responses were assessed in 90 infant squirrel monkeys born from normal and stressed pregnancies. Repeated psychological disturbance during pregnancy, evoked by disruption of the pregnant female's social relationships, significantly altered the performance of the young infant on a standardized battery of neuromotor tests. As compared with infants from undisturbed pregnancies, infants from chronically stressed pregnancies had poorer motor abilities, impaired balance reactions, and reduced postrotary nystagmus. They also had shorter attention spans and looking episodes during the administration of orientation items. In contrast, when only a single stressful period was imposed during midgestation, infants were not significantly different from control subjects. These findings indicate that sustained stress across pregnancy can have deleterious effects on fetal development, but a short period of stress, at least when restricted to midgestation, does not appear to adversely affect neuromotor responses of the young primate infant. PMID- 8473529 TI - Development in children's causal theories of their seizure disorders. AB - Despite the prevalence of seizure disorders in children, little is known about how youngsters with epilepsy understand the cause of their disorder. Fifty children and adolescents with idiopathic seizure disorders, between 5- and 16 years-old, were questioned about the etiology of seizure episodes and of seizure disorders, as well as their understanding of physical causality, general illness causality, and brain functioning. Responses were scored for their conceptual complexity according to scales paralleling Piaget's stages of cognitive development. Older children had more cognitively sophisticated concepts of epilepsy than did younger children. Overall, however, children scored significantly lower on questions about their seizure disorders than on questions assessing their understanding of physical causality, general illness causality, and brain functioning. Many children had misconceptions about seizure disorders and lacked disease-related information; only 41% of the children identified epilepsy as a disease involving the brain. These findings underline the need for including educational intervention in the comprehensive care of pediatric seizure disorders. PMID- 8473530 TI - In the eyes of the beholder: family and maternal influences on perceptions of adjustment of children with a chronic illness. AB - Investigation of the adjustment of children with a chronic illness has been complicated by an imprecise definition of adjustment, immense diversity in the kinds of chronic illnesses studied, and multiple instruments and sources of measurement of the child's behavior. In this study we have used a composite construct of adjustment, looked separately at reports from three separate observers of children's behavior, and limited our investigation to a few discrete types of illnesses. The investigation explores the contribution of selected characteristics of mothers and of families to children's adjustment as reported by children, their mothers, and their teachers. Family interactions were important to the psychological adjustment of all children (healthy or with a chronic illness and independent of age and socioeconomic status) as reported by all three observers. The mother's self-esteem and reported size of her social network were not associated with children's adjustment, but the mother's health locus of control beliefs interacted with the child's intelligence to predict children's adjustment. The pattern of these associations was different for different illness groups and for each of the three observers. PMID- 8473531 TI - Improved maintenance of plaque control by electrical toothbrushing in periodontitis patients with low compliance. AB - Patients showing low compliance with oral hygiene were selected from a population of patients referred for specialist treatment of periodontitis. The patients selected did not show an acceptable plaque control in spite of a prolonged training period. Plaque around 40% of the tooth surfaces, documented over a period of 4 to 40 months of frequent information and instructions, was found in 10 patients around the age of 40 years with a marked overrepresentation of men. Substitution of the ordinary toothbrush with an electrical toothbrush using the same working principles, resulted in a decreased plaque score of approximately 10% maintained over a considerable time period (12-36 months). A common complaint among the patients was that the oral hygiene procedures were time-consuming and cumbersome. They considered the electrical toothbrush as simple and time saving. Even if these possibilities were not investigated, merely the patients' positive attitude may have made the efforts of tooth cleaning including the proximal cleaning more tolerable, thus improving the compliance. Contributing to the improved compliance might also have been the electrical toothbrush per se. The cleaning technique allows the patient to concentrate on aiming the bristles at the gingival sulcus, while the brush makes the movements. In conclusion, it should be worthwhile recommending an electrical toothbrush with simple working technique to low compliant periodontitis patients restricting the recalls to twice a year. PMID- 8473532 TI - The effects of Acacia arabica gum on the in vitro growth and protease activities of periodontopathic bacteria. AB - The antibacterial activity of acacia gum was assessed using fresh isolates and reference strains of Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola. A fine aqueous suspension of gum was produced by sonication and then a soluble fraction isolated by centrifugation and membrane filtration. These preparations were incorporated into columbia agar at doubling concentrations. Growth of P. gingivalis and P. intermedia cultures on the agar was inhibited by whole gum sonicate at concentrations of 0.5-1.0% w/v. Both species showed reduced susceptibility when horse blood was present in the agar. The gum soluble fraction did not inhibit growth of any bacterial culture. The effect of acacia on bacterial proteases was examined with cell sonicates from log phase broth cultures. Enzyme activities were determined by fluorimetric assay with various synthetic peptide substrates. Most protease activities reduced in the presence of 0.5% w/v gum sonicate, with the trypsin-like activities of P. gingivalis and P. intermedia proving most sensitive. The gum soluble fraction was nearly always less inhibitory than the sonicate. The action of acacia gum against suspected periodontal pathogens and their enzymes suggests that it may be of clinical value. PMID- 8473533 TI - Comparability and discriminating power of 4 plaque quantifications. AB - This study was designed for analysis of the discriminating power of 4 different quantifications of supragingival plaque: (1) plaque wet weight (PWW); (2) the plaque index (PlI); (3) the PLQ index measuring the coronal extension of plaque; (4) the area % of stained plaque. Different quantities of plaque were produced by adding chlorhexidine acetate (CHX), hydrogen peroxide (H2O2), or sucrose to experimental chewing gums. Total mean scores of 12 subjects in each of 3 test groups revealed that chewing of CHX gum resulted in the lowest plaque scores with all 4 quantifications and that the highest scores were recorded for the PWW or PlI of the sucrose gum users. Chewing of the H2O2 gum produced as much plaque as the sucrose gum when evaluated according to the PLQ index and exceeded the sucrose gum scores when evaluated according to the area % index. The PWW discriminated best between low, medium and high plaque scores after chewing of both CHX, H2O2 and sucrose gums. PlI scores 1 and 3 remained stable whereas the frequency of PlI score 0 strongly decreased and that of score 2 strongly increased when going from gums producing low (CHX) and medium (H2O2) to large (sucrose) amounts of plaque. The PLQ index discriminated well between low and medium but poorly between medium and large amounts of plaque. The area % index functioned well when subjects with low (CHX) and medium (H2O2) plaque scores were subgrouped into those with < 30%, 30-70% or > 70% of their tooth surfaces covered with stained plaque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473534 TI - A comparison of methods to assess marginal bone height around endosseous implants. AB - 3 methods of measurements of marginal bone level on intra-oral radiographs of endosseous implants are described: measurements with a computerized image analysis system, with a magnifying-glass and with a digital sliding gauge. The accuracy of each of these methods was investigated and compared. The intra- and inter-observer error analysis showed that determining the precise bone height on the image is responsible for a large standard deviation for each method. It is concluded that measurements with a digital sliding gauge are preferable because it is easy to put into practice, and in addition, accuracy matches the accuracy of the other methods. PMID- 8473535 TI - Periodontal healing in teeth with periapical lesions. A clinical retrospective study. AB - The purpose of the present investigation was to compare clinical periodontal healing in periodontally involved teeth with and without pulpal pathosis. The investigation was conducted as a retrospective study on a consecutive referral population. The periapical conditions in endodontically involved single-rooted teeth from a selected patient sample were evaluated and correlated with their periodontal healing pattern. Multiple regression analysis of the registered variables showed that initial mean pocket depth and time elapsed after treatment significantly influenced change in pocket-depth. Non-surgical treatment of periodontal pockets exceeding 2.5 mm in teeth with horizontal marginal defects, over the observation period, showed significantly reduced mean pocket depth reduction in teeth with periapical pathology compared to teeth without periapical pathology. It was, furthermore, evident that proximal restorations, abutments for fixed bridges and root fillings with and without dowels did not significantly influence pocket depth reduction in the present material. It was concluded, based on the present results, that a root-canal infection, evident as a periapical radiolucency, if left untreated may in the long term perspective result in retarded or impaired periodontal healing following periodontal therapy and, consequently, should be given appropriate consideration when coordinating endodontic therapy and periodontal treatment. PMID- 8473536 TI - Meta-analysis of surgical versus non-surgical methods of treatment for periodontal disease. AB - A meta-analysis was performed on 5 randomized controlled trials comparing surgical with non-surgical treatment for periodontal disease. The specific procedures considered were the modified Widman flap compared with scaling and root planning or curettage with anesthesia. We chose the most consistently reported outcomes, pocket depth and attachment level, for analysis. At 1 year of follow-up, surgical treatment reduced pocket depth more than non-surgical for all initial levels of disease, but by 5 years, only the deepest initial pockets (> 7 mm) showed significant improvement over non-surgically treated teeth (0.51 mm reduction, p < 0.01). Attachment level showed significantly better early results for non-surgical treatment for less diseased teeth, but by 5 years, all significant differences had disappeared. We computed quality scores following a method described by Chalmers. The mean quality score for study data analysis and presentation was 0.37 +/- 0.009 and for the study protocol, the mean quality score was 0.19 +/- 0.002. We find that this meta-analysis supports findings relating response to therapy with initial level of disease severity. We also find that the choice of outcome measure influences the choice of therapy, with surgical therapy providing greater benefit for probing depth and non-surgical therapy providing greater benefit for attachment level. These results must be viewed, however, in light of the low quality scores of the evaluated studies and the potential for bias due to lack of binding, the small mean treatment differences, and the observer measurement variability. PMID- 8473537 TI - Periodontal disease in an Amish population. AB - Epidemiological studies of periodontal disease have attempted to focus on defined groups in which the variables thought to be responsible for disease could be controlled or more easily identified. This study documents periodontal disease parameters in a unique population of Amish farmers. A total of 371 Amish were contacted and 282 were examined in their homes giving a participation rate of 76%. Ages ranged from 18 to 79 years. Overall means for periodontal conditions were 1.54 mm for attachment loss, 2.63 mm for pocket depth, 0.17 for calculus, 0.63 for plaque and 0.61 for gingivitis. One dental examiner conducted all examinations. Prevalence of periodontal disease tended to be higher among males and increased with age. The majority of Amish examined had little evidence of destructive periodontal disease; about 3.4% of teeth examined had attachment loss of 6 mm or more. These findings indicate a modest level of periodontal disease among the Amish. It is of interest that this population does not generally seek routine dental care. Preliminary analyses of health behavior data collected indicate a lack of regular oral hygiene practices. It appears that the Amish may have protective factors which affect their level of disease. PMID- 8473538 TI - The plaque-removing efficacy of an oscillating/rotating toothbrush. A short-term study. AB - The purpose of the present study was to test the effectiveness of a new type of BRAUN electric toothbrush (D5) in comparison with the traditional BRAUN electric toothbrush (D3) and to a manual toothbrush (M). For this study, 60 dental students were selected who had no previous experience with the use of an electric toothbrush. The study consisted of 3 experiments. Prior to each experiment, all students were asked to abstain from all oral hygiene procedures for at least 24 h. In Exp I, the efficacy of toothbrushing was studied when one of the investigators brushed the teeth of the students. No toothpaste was used in this first part of the study. In Exp II, the efficacy of brushing was evaluated when the brushing was carried out by the students themselves. In Exp III, the efficacy of the brushing was studied after the students had received a professional instruction and oral prophylaxis. The available time for the brushing amounted to a total of 2 min per mouth. The amount of dental plaque was evaluated by means of the Silness and Loe plaque index at 6 sites around the tooth. Results showed in Exp I that both electric toothbrushes proved to remove significantly more plaque than the manual toothbrush (M 78%; D3 85%; D5 86%). In Exp II, no significant differences in plaque-removing efficacy were found between the 3 brushes (M 73%; D3 72%; D5 73%). In Exp III, the D5 proved to remove significantly more plaque than the other two brushes (M 77%; D3 77%; D5 83%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473539 TI - Effect of rinsing time on antiplaque-antigingivitis efficacy of listerine. AB - This double-blind, controlled clinical study compared the effectiveness of 30- and 60-s listerine rinses in both inhibiting the development of, and reducing existing, supragingival plaque and gingivitis, using an experimental gingivitis model. 94 subjects completed this study. For each subject, a modified gingival index, modified Quigley-Hein plaque index and Eastman interdental bleeding index were recorded at baseline and at 2 weeks. Following the baseline examinations, subjects received half-mouth prophylaxes, and began 2 x daily supervised rinsing either with listerine for 30 or 60 s or with a control mouthrinse for 30 s as their sole oral hygiene measure. Statistical analysis (ANCOVA) showed that both the 30- and 60-s listerine rinses were significantly (p < 0.01) more effective than the control in inhibiting and reducing plaque, gingivitis and gingival bleeding. Although 60-s rinses with listerine were significantly more effective (p < 0.01) than 30-s rinses in controlling plaque, the 2 rinse durations were similarly effective in controlling interdental bleeding and gingivitis. This study confirms the recommendation of 2x daily rinsing with listerine for 30 s as an effective regimen for gingivitis control. PMID- 8473540 TI - Gingival hyperplasia in renal allograft recipients receiving cyclosporin-A and calcium antagonists. AB - Although it is established that the immunosuppressant cyclosporin-A (CsA) and calcium antagonists [Nifedipine (Nif) and Diltiazem (Dz)] can independently induce gingival enlargement, little has been documented on the significance of the salivary CsA levels and the combined effect of CsA and a calcium antagonist upon gingival tissues. In the present cross-sectional investigation, clinical periodontal parameters and the pharmacologic profiles of CsA, Nif, and Dz were determined for 66 renal transplant recipients. Subjects were divided into the following groups: Group (Gp) 1: CsA [n = 18]; Gp 2: CsA + Nif [n = 15]; Gp 3: CsA + Dz [n = 12] and a negative Control Gp 4: azathioprine [n = 21]. A gingival enlargement score was assessed for each patient from study models using a hyperplastic index (HI). Pharmacologic profiles included CsA whole blood and whole saliva levels as measured by fluorescence polarization immunoassay. The HI scores between Gp 1, 2 and 3 were not significantly different. However, when compared with controls (Gp 4), there was a significant difference in HI and all individual groups (Gp 1, 2, 3) (p < 0.05). Gingival hyperplasia was only weakly related to plaque and calculus but was unrelated to CsA dose (mg/kg/day), duration of CsA therapy (months), CsA blood or saliva levels (ng/ml), or the concurrent administration of a Nif or Dz. Gingival enlargement was found to occur in 49% of subjects who were either on CsA or CsA and a calcium antagonist. It is concluded that CsA alone or in combination with a calcium antagonist caused a significant increase in gingival enlargement compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473541 TI - Prevention of transmission of resistant bacteria between periodontal sites during subgingival application of antibiotics. AB - This study was designed to investigate whether antibiotic resistant micro organisms are able to contaminate and survive on syringe tips used for subgingival deposition of antibiotics, and to test simple and effective means of disinfecting the syringe tip between applications. In the first part of the study, syringe tips used for application of Minocycline subgingival formula in 20 adult periodontitis patients were cultured for bacteria resistant to this drug before and after disinfecting them with ethanol. The results showed that 80% of the unwashed syringes were culture positive for minocycline resistant bacteria, whereas only 1 ethanol washed syringe tip was contaminated. In part II of the study, after dispensing minocycline periodontal formula in 20 patients, 10 of the syringe tips were washed with ethanol while 10 were left untreated. All syringes were stored in a refrigerator for 8 days, whereafter the tips were sampled for resistant bacteria. 20% of the unwashed tips were contaminated after 8 days incubation at 4 degrees C. None of the ethanol washed syringe tips were culture positive. We conclude that syringe tips may be contaminated with antibiotic resistant bacteria after dispensing the antibiotic in periodontal pockets. The transmission of these bacteria to other periodontal sites may be avoided by disinfecting the syringe tip with ethanol between applications. We have also shown that antibiotic resistant bacteria may survive on the syringe tip following 8 days storage in a refrigerator, suggesting that syringes used for subgingival deposition of an antibiotic should not be stored for reuse. PMID- 8473542 TI - Industry under siege. PMID- 8473543 TI - Cocaine abuse in North America: a milestone in history. AB - The euphoric effects of coca leaves have been known to mankind for thousands of years. Yet the first epidemic of cocaine use in America occurred during the late 19th century. Initially, there were no laws restricting the consumption or sale of cocaine. In fact, cocaine was freely available in drug stores, saloons, from mail-order vendors, and even in grocery stores. It is reported that one drug manufacturer, in 1885, was selling cocaine in 15 different forms, including cigarettes, cheroots, inhalants, cordials, crystals, and solutions. Many famous imported wines, such as "Vin Mariani," contained a mixture of wine and coca. For consumers on budgets, the wonder drug was available as Coca-Cola and dozens of other soda pops and pick-me-up drinks. One of them even had a simple and direct name, Dope. Soon enough, the ill effects of cocaine became apparent, and by the 1920s cocaine was the most feared of all illicit drugs. Most states began enacting laws against cocaine use. President William Taft proclaimed cocaine as Public Enemy No. 1, and in 1914 the Congress passed the Harrison act, which tightly regulated the distribution and sale of cocaine. By the late 1950s, cocaine use in the United States was simply considered a problem in the past. Unfortunately, the people who were aware of the nation's first cocaine epidemic gradually passed away, and America once again was ready for its fling with cocaine in the 1960s. Today, it is estimated that upwards of 50 million Americans, that is one in four, have used cocaine. In addition, another fifty thousand people use this substance for the first time each day. More than 6 million Americans use cocaine on a regular basis. Little wonder, then, that America as well as the other countries have declared a "War on Drugs." In this review, pharmacology of cocaine, major complications arising from its use, and efforts to curb its abuse are discussed. PMID- 8473544 TI - Teaching clinical pharmacology: a process of 'lifelong learning'. PMID- 8473545 TI - Immunopharmacology and adverse drug reactions. AB - Adverse drug reactions are common and troublesome complications of contemporary pharmacotherapy. Adverse drug reactions are frequently, and often incorrectly, referred to as "allergy". Although there are multiple mechanisms for adverse drug reactions, adverse drug reactions mediated by the immune system account for a disproportionate number of fatal and serious adverse reactions, and constitute a major clinical problem for patients and physicians. The immune system has evolved in multicellular organisms as a defence against infection. Interactions between drugs and the immune system occur as inadvertent consequences of the protective function of the immune system, with drug molecules or drug-carrier haptens being recognized as "non-self" by the immune system. The classical mechanisms for drug hypersensitivity described by Gell and Coombs (Types 1 to 4) include IgE mediated, cytotoxic, immune complex-mediated and delayed mechanism. These mechanisms provide elegant models for drug-immune interactions that can provide mechanistic explanations for events such as urticaria associated with penicillins. However, these mechanisms do not account for many of the immunologically mediated adverse reactions commonly encountered in clinical practice. Over the last two decades, there has been an increasing awareness of the importance of reactive drug metabolites and drug-protein interactions in the initiation of immunologic events mediating adverse drug reactions. Reactive drug metabolites may produce direct and profound effects on various functions of the immune system. Although some adverse reactions mediated by the immune system occur with equal frequency among adults and children, some of these reactions appear to be markedly more common among children than adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473546 TI - Hemofiltrability of histamine H2-receptor antagonist, nizatidine, and its metabolites in patients with renal failure. AB - To study if an H2-receptor antagonist, nizatidine, and its metabolites [N-2 monodesmethylnizatidine (N-2-MDMN) and nizatidine sulfoxide (nizatidine S-Ox)] would be removed by an arteriovenous hemofiltration, the authors measured their plasma concentrations and amounts recovered in ultrafiltrate during 11 sessions of an intermittent hemofiltration performed in seven patients with renal failure who were given an oral administration of nizatidine (150 mg). The concentrations of the parent drug and its metabolites in plasma and ultrafiltrate were determined with a high-performance liquid chromatography with ultraviolet absorbance detection. The mean (+/- standard deviation [SD]) amounts of nizatidine removed by the procedure performed at the mean ultrafiltration rate of 18 (range, 11-25) mL/min over the mean duration of 179 (60 to 300) minutes accounted for 1.9 +/- 1.4% of the dose administered. The corresponding values for N-2-MDMN and nizatidine S-Ox were 0.3 +/- 0.2% and 0.2 +/- 0.2% of the molar dose of nizatidine, respectively. There was a significant correlation between the filtration rate and the hemofiltration clearance of nizatidine (r = .94, P < .001) or its active metabolite, N-2-MDMN (r = 0.83, P < .01), indicating that the sieving coefficient (Sc), an index of filtration efficiency, for these compounds is largely constant (0.59 and 0.67 for nizatidine and N-2-MDMN, respectively) under the current hemofiltration conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473547 TI - Effect of concomitantly administered cimetidine or ranitidine on the pharmacokinetics of the 5-HT2-receptor antagonist ritanserin. AB - The effects of concurrent administration of either cimetidine 800 mg once daily or ranitidine 300 mg once daily on the single-dose pharmacokinetics of ritanserin 10 mg were investigated in an open, randomized three-way cross-over, controlled investigation in 9 healthy volunteers. Concurrent administration of cimetidine had no significant effect on the area under the plasma concentration-time curve of ritanserin compared with control experiments. The maximum plasma concentration of ritanserin was decreased significantly (105.0 +/- 9.2 versus 125.0 +/- 13.8 ng/mL; P = .0039), whereas time to reach maximal concentration (tmax) of ritanserin was only slightly but not significantly increased, if the subjects were pretreated with cimetidine. After concurrent ingestion of ranitidine, only a trend to a decrease in the maximum plasma concentration of ritanserin was observed. Time to achieve the maximum plasma concentration, terminal half-life of elimination, and the total area under the plasma concentration-time curve of ritanserin were not altered in comparison with control experiments. The results of the study show that concurrent treatment with cimetidine 800 mg once daily or ranitidine 300 mg once daily has no apparent effect on the systemically available amount of ritanserin after a single oral dose of 10 mg. Both H2-antagonists cause a significant (cimetidine) or borderline significant (ranitidine) decrease of the maximum plasma concentration of ritanserin and a slight but not significant increase in tmax (cimetidine). These effects are of minor clinical importance and seem most likely be due to a decrease of the rate of absorption of ritanserin during concurrent administration of cimetidine/ranitidine. PMID- 8473548 TI - High-calcium diet in spontaneously hypertensive rats: intervention with calcium antagonist verapamil. AB - A number of studies have shown an antihypertensive effect for high-calcium diets, but others have found no effect or, even a prohypertensive effect. Because of these disparate results, studies were conducted in spontaneously hypertensive rats (SHR) fed either a normal calcium diet (1.0% calcium) or a high-calcium diet (4.0% calcium) with or without verapamil HCl (50 mg/kg body weight) from ages 5 to 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured by indirect tail cuff method. During the analysis of the electrolytes and vasoactive hormones monitored in this study, it was found that rats fed high-calcium diet had significantly elevated serum ionized and total calcium and calcium excretion. Systolic blood pressure for the verapamil-normal calcium diet (week 5, 148 +/- 4 mm Hg; week 7, 162 +/- 4 mm Hg) did not differ significantly from that of normal calcium diet (week 5, 152 +/- 2 mm Hg; week 7, 160 +/- 1 mm Hg). The high-calcium diet potentiated the development of hypertension, i.e., SBP was (157 +/- 2 mm Hg) on the 5th week and (174 +/- 4 mm Hg) on the 7th week. Conversely, verapamil high calcium diet prevented the development of hypertension (week 5, SBP was 139 +/- 4 mm Hg; week 7, SBP was 146 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473549 TI - Antihypertensive action of heparin: role of the renin-angiotensin aldosterone system and prostaglandins. AB - Chronic subcutaneous administration of heparin consistently lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Groups of spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats were treated with subcutaneous heparin (700 U/d) for 6 weeks. Weekly determinations of systolic blood pressure (tail-cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins (PGs) (PGF2 alpha, PGI2), thromboxane A2, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II, and norepinephrine, were determined. As before, heparin produced a significant (P < .01) decrease in hematocrit in both SHRs and NWRs, but a parallel decrease in blood pressure was noted only in SHRs. A significant (P < .001) increase in plasma renin activity was found in heparin-treated SHRs and NWRs; however, a corresponding elevation of plasma aldosterone level was noted only in heparin treated NWR. Plasma aldosterone level significantly (P < .01) decreased in heparin-treated SHRs. Plasma PGs and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoconstrictor substances were essentially similar among the heparin-treated and control groups. These findings suggest that PGs or kallikrein have a slight or no role in determining the antihypertensive effect of heparin. Conversely, the results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism of heparin. PMID- 8473550 TI - Short- and long-term effects of spirapril on renal hemodynamics in patients with essential hypertension. AB - Sixteen essential hypertensive patients were entered into a protocol assessing the effect of Spirapril, an angiotensin-converting enzyme (ACE) inhibitor, on blood pressure, the renin-aldosterone system, and renal function. Specifically monitored before, during 6 weeks, and 6 months of Spirapril therapy were plasma renin activity, plasma aldosterone, serum ACE, the renal clearances of creatinine, inulin, and para-aminohippurate, and urinary albumin excretion. Blood pressure was well controlled. Spirapril stimulated plasma renin activity and suppressed ACE throughout the entire protocol. Renal clearances were unchanged. Renal vascular resistance was decreased. Urinary albumin excretion was decreased. The authors conclude that the ACE inhibitor, Spirapril, when used as an effective antihypertensive agent, preserves renal function, lowers renal vascular resistance, and decreases urinary albumin excretion. PMID- 8473551 TI - Pharmacokinetics of clentiazem after intravenous and oral administration in healthy subjects. AB - This study characterized the pharmacokinetics of clentiazem (CLZ) after a single intravenous bolus (IV) and oral (PO) dose in humans. Twenty-four healthy male subjects (28.5 +/- 5.2 years; 77 +/- 8.2 kg) received IV (20 mg) and PO (80 mg) doses of CLZ as part of a four-way, randomized, complete crossover study. Serial blood samples were drawn up to 48 hours after administration of the drug. Plasma samples were analyzed for CLZ and three metabolites by a high-pressure liquid chromatography method. The values (mean [CV, %]) for systemic clearance, volume of distribution at steady-state, and half-life of CLZ were 63.6 L/hour (23.5), 756.1 L (19.1), and 10.6 hours (33.1), respectively, after IV administration. The peak plasma CLZ concentration (Cmax) and time to Cmax were 37.0 ng/mL (38.7) and 3.7 hours (22.9), respectively, with a lag time after PO administration. The absolute bioavailability of PO CLZ was 45% (30.7). The ratio of area under the curve of N-desmethyl CLZ to that of CLZ increased from 0.15 (57.0) after IV to 0.60 (21.4) after PO administration, suggesting a significant first-pass effect. The mean residence time and mean absorption time of CLZ were 12.3 hours (24.3) and 3.1 hours (88.1), respectively. The plasma concentration-time data of CLZ can be described by either a one- or two-compartment pharmacokinetic model. PMID- 8473552 TI - Hypoglycemic and insulin response to a continuous intravenous infusion of CGP 35126 recombinant human insulin-like growth factor-I (rhIGF-I) in healthy males. AB - Recombinant human insulin-like growth factor-I (rhIGF-I) produced by expression in a yeast vector was evaluated in seven normal men to determine effects on plasma glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/hour. Each infusion lasted for 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (P > .05) from their pre-dose levels. Compared with the saline (control) infusion, serum glucose levels were statistically lower (P < .05) 2 hours into the rhIGF-I infusion. These lower glucose levels were maintained until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. This observation suggests that suppression of insulin levels may be due to secondary hypoglycemia rather than to a direct rhIGF I effect. This study demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic states. PMID- 8473553 TI - A phase I dose-ranging safety and pharmacokinetics study of a novel oral thromboxane synthase inhibitor, FCE 22, 178. AB - A 100- to 3200-mg dose range of FCE 22,178 was studied in this phase I single dose escalation safety/kinetics study. After oral administration, a rapid drug absorptive phase and a biexponential disposition profile were observed. Mean estimates of the terminal elimination half-life of FCE 22,178, over the doses studied, ranged from 7.6 to 14.4 hours. A disproportionate increase in both maximum peak plasma concentration (Cmax) and area under the curve (AUC0-infinity) was noticed for doses higher than 400 mg. Mean estimates of systemic clearance (CLs/F) over the 100- to 400-mg doses were 0.053 to 0.064 L/hour/kg, and were significantly higher for the three higher dose levels. This nonlinearity appears to be related to the changes in oral bioavailability. Estimates of distribution volume (Vd, lambda z/F) for FCE 22,178 increased from 0.75 L/kg at the 100-mg dose to 3.00 L/kg at the 3200-mg dose, and renal clearance (CLr) also increased with dose. Both observations may be related to an increase in free fraction of FCE 22,178 at higher doses. Urinary excretion of unchanged drug averaged < 10% for all dose levels. The urinary excretion of the glucuronide metabolite (M1) averaged 41 to 70% for doses up to 400 mg, but diminished to 13% at the 3200-mg dose. The disposition of M1 appeared to be formation-rate limited. In addition, the ratio of the formation to the disposition clearance for M1 was relatively stable and apparently dose independent. No drug-related adverse experiences were observed over the studied dose range after single doses at FCE 22,178. PMID- 8473554 TI - Effect of food and a monoglyceride emulsion formulation on danazol bioavailability. AB - The bioavailability of a single 100-mg dose of danazol delivered from the commercial formulation (hard gelatin capsule) and from an experimental lipid emulsion formulation of danazol was studied in 11 healthy female volunteers in both fed and fasted states. The emulsion formulation (fasted) increased bioavailability fourfold compared with the capsule (P = .0001); the difference, however, was not significant in the fed state. Food increased the bioavailability of the capsule formulation more than threefold over fasted administration (P = .0001). In a separate study of 12 female volunteers, single doses of the emulsion formulation of danazol administered with food demonstrated essentially dose proportional pharmacokinetics over the dose range studied (50-200 mg). The authors conclude that factors that increase the extent of solubilization lead to significant enhancement in the bioavailability of danazol. PMID- 8473555 TI - Rabies: a review. PMID- 8473557 TI - The enigma of the proliferative enteropathies: a review. PMID- 8473556 TI - Neurones in autonomic ganglia of normal horses contain phosphorylated neurofilaments. AB - Neurofilaments (NF) are composed of three polypeptides of differing molecular size, termed NF-L, NF-M and NF-H. The NF-H and, to a lesser degree, NF-M components are phosphorylated. In the majority of normal neurones, the location of phosphorylated NF is confined to neuronal processes, particularly the axon, and excluded from the perikaryon. Cell bodies of autonomic neurones of the rat do not contain phosphorylated NF. In many disease states, phosphorylated NF accumulate in the neuronal cell body and therefore in most circumstances their presence indicates abnormality. This paper reports that in at least two autonomic ganglia of normal horses (stellate and coeliomesenteric) the vast majority of neuronal perikarya immunostain strongly for phosphorylated NF. Pretreatment with alkaline phosphatase abolishes staining. PMID- 8473558 TI - The relationship of the canine acanthomatous epulis to ameloblastoma. AB - This paper compares the microscopic features and clinical behaviour of the acanthomatous epulis in dogs with those of ameloblastoma in human beings. The acanthomatous epulis has similar microscopic features to one histological variant of human ameloblastoma, the acanthomatous ameloblastoma. Moreover, its clinical behaviour is equivalent to that of intraosseous ameloblastoma in human beings, not of the human peripheral (extraosseous) ameloblastoma, as has been suggested. The stroma of acanthomatous epulides varies and does not always resemble periodontal ligament, a feature that in dogs has been used to distinguish them from ameloblastomas. It is concluded that the acanthomatous epulis (1) is an ameloblastoma, (2) arises from the gingival epithelium in some cases, but (3) may also arise intraosseously and then break out of bone. We recommend the term canine acanthomatous ameloblastoma as being appropriate for this lesion. PMID- 8473559 TI - Metastasis of a myxoid leiomyosarcoma via the renal and hepatic portal circulation in a sarus crane (Grus antigone). AB - A 12-year-old female sarus crane (Grus antigone) developed a recurrent proliferative lesion in the subcutaneous tissue of the tarsometatarsus, which failed to respond to medical and surgical therapy. The crane was killed and microscopic examination of the tissues taken at necropsy revealed a myxomatous, poorly-differentiated sarcoma with metastasis to the liver and kidney. Immunohistochemical staining for muscle actin, smooth muscle myosin and vimentin were positive, indicating that the primary and metastatic tumours were leiomyosarcomas. Location of the metastatic lesions in only the portal venous system of the liver and veins of the kidney indicated that the route of metastasis was the portal circulation via the ischiatic vein, caudal mesenteric vein and both the renal-portal shunt and hepatic portal vein. This is the first report of metastatic subcutaneous leiomyosarcoma in an avian species. PMID- 8473560 TI - Morphological and functional disturbances in pulmonary vascular endothelium following exposure of sheep to an "avirulent" strain of Pasteurella haemolytica. AB - Sheep were vaccinated with a live attenuated strain of Pasteurella haemolytica and killed 3 days later. Segments of main intrapulmonic artery and vein were removed for biophysical and scanning electron microscopic studies. In the pulmonary artery, vaccination with Pasteurella haemolytica caused an increase in the number of endothelial cell surface blebs and, in some cases, those blebs appeared to be splitting open, suggesting cell damage or irritation. There was a surprising lack of platelet adherence to the lesions, suggesting that an antiplatelet factor is released by the damaged endothelium. The endothelial dependent relaxant response to bradykinin was enhanced following vaccination. In the pulmonary vein, ultrastructural lesions similar to those in the artery were present in vaccinated animals. Bradykinin caused a contraction, an effect that was reduced following vaccination with Pasteurella haemolytica. These experiments demonstrate that a live, vaccine-derived strain of Pasteurella haemolytica causes both morphological and functional changes in the pulmonary vascular endothelium. PMID- 8473561 TI - Effects of Pasteurella multocida toxin on the osteoclast population of the rat. AB - Pasteurella multocida type D toxin is a peptide shown to induce severe atrophic rhinitis in the pig as the result of an increased osteoclastic resorption of the ventral nasal turbinates. In the present study, the effects of the toxin on the histological, cytochemical and ultrastructural features of the osteoclast population of the rat were examined. Pasteurella multocida toxin induced atrophy of the ventral and dorsal nasal turbinates and thinning of the nasal bones. The number and size of the long bone metaphyseal osteoclasts were significantly increased, but not the number of nuclei per cell. Osteoclasts of toxin-treated rats had more developed clear zones and ruffled borders than those of the controls and their cytoplasmic vacuoles were more abundant and larger. We concluded that P. multocida toxin stimulates bone resorption by osteoclasts in the rat by increasing resorption activity and by increasing their number. Its action is not limited to the nasal turbinates but occurs also in the other bones, such as the long bones. PMID- 8473562 TI - Pathology of experimental traumatic craniocerebral missile injury. AB - The neuropathological alterations in sheep associated with head wounds inflicted by a .22 calibre rifle are reported. Brain damage was manifest as a permanent haemorrhagic wound cavity produced by crushing and laceration of tissue during missile penetration, secondary tracks due to bone and bullet fragments, widely distributed stretch injuries to blood vessels, nerve fibres and neurons as a consequence of the radial forces of the temporary cavity which develops as a bullet penetrates tissue, marked subarachnoid and intraventricular haemorrhage, and distortion and displacement of the brain. PMID- 8473563 TI - Preliminary findings of alterations in serum alkaline phosphatase activity in chickens during coccidial infections. AB - Two-week-old broiler chickens were inoculated orally with various doses of avian Eimeria that infect different sections of the intestine. The coccidia used were E. acervulina (duodenum), E. maxima (jejunum), E. brunetti (ileum) and E. tenella (caecum). The measurements evaluated were weight gains, intestinal lesion scores and changes in serum alkaline phosphatase (SAP) activity 6 days after infection. SAP activity was inversely proportional to both oocyst dose and gross intestinal lesion score, and directly proportional to weight gains with infections of E. acervulina, E. maxima and E. tenella. However, no significant changes in the SAP activity were found in those birds infected with E. brunetti. Taken together, the data suggest that SAP activity may be a sensitive marker of the pathogenesis of certain coccidial infections, especially in the duodenum, jejunum and caecum, that may be used as an additional factor in evaluating coccidial control measures. PMID- 8473564 TI - Comparison of pathological signs of disease in specific-pathogen-free calves after inoculation of the respiratory tract with Ureaplasma diversum or Mycoplasma canis. AB - To confirm the pathogenic role of Ureaplasma diversum in respiratory disease of calves, we inoculated caesarean-delivered, colostrum-deprived calves intranasally with a dose of 10(7) colour-changing units (CCU) or endobronchially with a dose of 10(10) CCU. Clinical signs of respiratory disease were not observed, but in the endobronchially inoculated calves, thick cuffs of round cells surrounded the bronchi, bronchioli and blood vessels, and a lobular catarrhal pneumonia developed. It was concluded that the pathogenicity of U. diversum can be demonstrated after endobronchial but not after intranasal inoculation. Similar calves were inoculated endobronchially with a dose of 2 x 10(10) colony-forming units of Mycoplasma canis. Clinical signs of respiratory disease were not observed. At day 2 after inoculation, only slight pathological signs of respiratory disease were detected, and these disappeared at day 9. M. canis was not recovered from the lungs. Hence, M. canis could not be clearly identified as a pathogen in respiratory disease of calves. By comparing the results of the various experiments, we concluded that thin cuffs of round cells in the lungs can indicate mycoplasma infections, but that these are not necessarily pathognomonic. PMID- 8473565 TI - Spontaneous neoplasia in the ferret (Mustela putorius furo). AB - Thirteen spontaneous tumours in ferrets from two laboratory breeding colonies are described, including two types not previously reported in this species, namely, uterine teratoma and neurilemmoma. The literature on tumours in laboratory and domestic ferrets is comprehensively reviewed from the first reported case in 1950. Only 20 cases were reported from 1950 to 1979, nearly all from laboratory or zoological collections. In the following 10 years more than 170 further cases were reported, about half of them in domestic pet ferrets. A review of the limited literature on tumours in related species reveals substantial incidences in black-footed ferrets and ranch mink allowed to live out their lifespan, and isolated cases in polecats and at least eight other species of Mustelidae. PMID- 8473566 TI - Synthesis and distribution of atrial natriuretic peptide (ANP) in hearts from normal dogs and those with cardiac abnormalities. AB - The cardiac distribution of immunoreactive atrial natriuretic peptide (IR-ANP) and ANP-specific mRNA was studied in 35 normal dogs and 44 dogs with primary and secondary heart abnormalities. According to clinical and pathological findings the dogs were assigned to seven groups: Group 1, normal young dogs (< 12 months); Group 2, normal adult dogs (> 12 months); Group 3, low to moderate hypertrophy; Group 4, severe hypertrophy; Group 5, dilated cardiomyopathy; Group 6, renal failure with secondary left ventricular hypertrophy; and Group 7, other heart abnormalities. In comparison with hearts of normal dogs, the amount of IR-ANP and ANP-specific mRNA was reduced in the atria and increased in the ventricles of dogs with hypertrophy and cardiomyopathy. The immunoreactivity in normal canine atria was far lower than in control rats and hamsters. The pattern of ventricular immunoreactivity was faint and patchy. Only in a few ventricular localizations of three dogs of Group 5 and one dog of Group 6 was there a granular pattern suggesting the presence of secretory granules. A state of intense secretory stimulation in cardiomyopathy was indicated by electron microscopy. Due to its low concentration and localized pattern, however, IR-ANP does not seem to be a reliable marker for the presence of hypertrophic or cardiomyopathic changes in dogs. PMID- 8473567 TI - Spread and distribution of Coxiella burnetii in C57BL/6J (H-2b) and Balb/cJ (H 2d) mice after intraperitoneal infection. AB - Spread and distribution of Coxiella burnetii were investigated immunocytochemically and antigen dissemination was correlated with light microscopic alterations in Balb/cJ (H-2d) and C57BL/6J (H-2b) mice. Intraperitoneal inoculation of C. burnetii resulted in a self-limiting systemic infection. Gross findings consisted of hepatosplenomegaly and histological lesions were characterized by microabscesses and granulomas in numerous organs including spleen, liver, mesentery, bone marrow, lymph nodes, pancreas, heart and uterus. In addition, splenic lymphoid depletion, venous microthrombi and reduction of bone marrow cells were observed. Coxiella burnetii antigen was demonstrated immunocytochemically in the aforementioned organs, especially in spleen, liver and most of all in the bone marrow. Coxiella antigen was detected in macrophages, macrophage precursor cells, and occasionally endothelial cells. Numerous C. burnetii antigen-positive cells were observed between 5 and 12 days post-infection; thereafter, the amount of C. burnetii antigen decreased rapidly. Immunopositivity was detectable until 30 and 44 days post-infection in the bone marrow of Balb/cJ and C57BL/6J mice, respectively. Severity of histological lesions was associated with presence and clearance of C. burnetii antigen. Specific IgM antibodies were detected 4 days after infection and IgG seroconversion was noticed 7 to 10 days post-infection. Coxiella burnetii specific IgM and IgG antibodies were still present 150 days after infection. Significant strain-specific differences in the antibody response were not found. The findings demonstrate systemic spread of C. burnetii, especially to bone marrow, spleen and liver, and antigen distribution was closely correlated with the appearance and degree of histological lesions. PMID- 8473568 TI - Cycloheximide or nordihydroguaiaretic acid protects mice against the lethal and hepatocytolytic effects of a combined challenge with D-galactosamine and bacterial endotoxin. AB - Both cycloheximide and nordihydroguaiaretic acid protect mice against the fatalities and associated panlobular hepatocyte necrosis that follow a challenge with D-galactosamine and bacterial endotoxin. It is proposed that cycloheximide acts as an inhibitor of the endotoxin-induced activation of phospholipase A2, thereby inhibiting the synthesis of leukotrienes which is now known to be a prerequisite for tumour necrosis factor-alpha (TNF) biosynthesis, the latter cytokine being regarded as the terminal mediator of the fatal D-galactosamine and endotoxin-induced syndrome. Nordihydroguaiaretic acid protection is explained by its inhibition of lipoxygenase enzymes, and thus ultimately of TNF production in response to endotoxin. PMID- 8473569 TI - Cell shape changes induced by sulphate in the Cloudman mouse melanoma cell line. AB - The mechanism of cell shape changes and haematogenous translocations (metastases) in mouse malignant melanoma cells induced by phorbol esters and protein kinase C (PKC) is reported as adhesion "downregulation", exocytosis and motility. However, PKC activation also produces intracellular alkalinization, a causal factor in plasma membrane internalization, cell rounding and detachment that does not necessarily implicate specific cell adhesion downregulation. We show here that Cloudman mouse malignant melanoma cells can be induced to round up and detach with concomitant intracellular alkalinization by simple inorganic sulphate treatment, thereby suggesting an alternative explanation to the reported phenomena. PMID- 8473570 TI - Introduction to special section: theoretical developments in the cognitive psychotherapies. AB - The cognitive psychotherapies have developed and substantially differentiated since their inception in the 1950s. Six major themes in their theoretical development are discussed: (a) the differentiation of rationalist and constructivist therapies and metatheories of knowing; (b) the acknowledgement of social, biological, and embodiment processes in therapy; (c) the recognition of unconscious processes; (d) an increasing focus on self-organizing and self protective processes in life span personality development, with such processes being embedded in interpersonal and social system dynamics; (e) a shift toward different views of emotionality and the incorporation of experiential techniques; and (f) a synergistic involvement in the psychotherapy integration movement. The cognitive psychotherapies reflect remarkable activity, a point illustrated and elaborated in the articles that constitute this special section. PMID- 8473571 TI - Cognitive therapy: past, present, and future. AB - Proponents of cognitive therapy have striven to establish this approach as a mature system of psychotherapy for over 3 decades. The theoretical formulations have been enriched by clinical extrapolations from the neopsychoanalysts and experimental findings from cognitive psychology. The therapeutic strategies and techniques have been refined as a result of interaction with behavior therapy, which also influenced the emphasis on empirical testing of the theoretical formulations and the therapeutic applications. Outcome trials have demonstrated efficacy in a number of common disorders. New emphasis on the crucial importance of specific formulations (especially dysfunctional beliefs) has provided important clues to the treatment of a large number of other disorders. I conclude that cognitive therapy has fulfilled the criteria of a system of psychotherapy by providing a coherent, testable theory of personality, psychopathology, and therapeutic change; a teachable, testable set of therapeutic principles, strategies, and techniques that articulate with the theory; and a body of clinical and empirical data that support the theory and the efficacy of the theory. PMID- 8473572 TI - Reflections on rational-emotive therapy. PMID- 8473573 TI - Changing conceptions of cognitive behavior modification: retrospect and prospect. AB - A retrospective analysis of cognitive behavior modification reveals that 3 major metaphors have been offered to explain the role that cognitions play in behavior change. These metaphors include cognition as a form of conditioning, information processing, and, currently, narrative construction. The implications of using each of these metaphors are discussed. PMID- 8473574 TI - An appraisal of cognitive therapy. AB - This review describes the development of cognitive therapy (CT) for depression in the 1960s and 1970s and its application to diverse clinical populations. The question of how CT works, in terms of both active therapeutic ingredients and mechanisms of change within the individual, is addressed. The limitations of CT are discussed, as well as recent developments and modifications of the therapy that have evolved in response to these perceived limitations and that bring it closer to other therapy approaches. The review concludes with some directions for future research. PMID- 8473575 TI - An appraisal of rational-emotive therapy. AB - Albert Ellis's rational-emotive therapy (RET) is scrutinized on several conceptual and empirical grounds, including its reliance on constructive assessment and its ethical stance. Its professional impact thus far exceeds its scientific status. Opinion varies on how even to define irrational beliefs; 1 consequence is problems in assessing them. Meta-analytic reviews provide support for the general utility of RET, but more qualitative reviews question both the internal and external validity of much of the published research. Lacking are process studies that can shed light on the mechanisms of therapeutic change, a situation likely due to the complexity of RET and to a lack of consensus as well about its very definition. Perhaps more progress can be achieved by forsaking studies of RET as a package and shifting instead to examination of specific therapeutic tactics in particular circumstances. PMID- 8473576 TI - An appraisal of constructivist psychotherapies. AB - Predicated on a postmodern epistemology, constructivist theories emphasize the proactive, self-organizing features of human knowing and their implications for psychotherapy. This article outlines the potential contributions of 4 clinical lineages sharing a constructivist philosophy--personal construct theory, structural--developmental cognitive therapy, narrative reconstruction, and constructivist family therapy--and briefly reviews emerging trends in psychotherapy research compatible with this perspective. Although current constructivist approaches confront problems as well as prospects, they represent a growing force within psychotherapy, contributing to the sophistication of psychological theory, the diversification of clinical research, and the extension of therapeutic technique. PMID- 8473577 TI - Cognitive-behavioral therapies with youth: guiding theory, current status, and emerging developments. AB - This article begins with a brief description of the guiding theory behind cognitive-behavioral interventions with youth, such as a therapeutic posture, an important cognitive distinction, and a specific treatment goal. Next, on the basis of a review of the literature, the nature of cognitive functioning, the treatments, and the outcome of treatment studies are described and examined for (a) aggression, (b) anxiety, (c) depression, and (d) attention-deficit hyperactivity. Conclusions and emerging developments are provided. PMID- 8473578 TI - Cognitive therapy of anxiety disorders. AB - A review of studies of cognitive-behavioral therapy (CBT) for generalized anxiety disorder, panic disorder with and without agoraphobia, and social phobia indicates that CBT is consistently more effective than waiting-list and placebo control groups. In general, CBT has proved more beneficial than supportive therapy as well. Comparisons with active behavioral treatments provide more variable results. Converging evidence suggests that cognitive change may be a strong predictor of treatment outcome, but that such change may be produced by a number of therapeutic approaches. Pretest-posttest change with CBT is depicted in meta-analytic summary form for each disorder. PMID- 8473579 TI - Cognitive treatments for eating disorders. AB - Cognitive-behavioral therapy (CBT) is applicable to all eating disorders but has been most intensively studied in the treatment of bulimia nervosa (BN). CBT is designed to alter abnormal attitudes about body shape and weight, replace dysfunctional dieting with normal eating habits, and develop coping skills for resisting binge eating and purging. CBT is effective in reducing all core features of BN and shows good maintenance of therapeutic improvement. Although superior to therapy with antidepressant drugs, CBT has not been shown to be consistently superior to alternative psychological treatments. Different hypotheses about CBT's mechanisms of action are discussed. PMID- 8473580 TI - Cognitive therapy for depression: conceptual issues and clinical efficacy. AB - Cognitive therapy has emerged as 1 of the most promising psychosocial interventions for the treatment of depression. It appears to be at least the equal of alternative interventions (including pharmacotherapy) with respect to acute treatment. In addition, there are indications that it may reduce risk of symptom return after treatment termination. Nonetheless, design limitations reduce the certainty with which such conclusions can be drawn. Furthermore, tests of its efficacy have largely been limited to nonbipolar outpatient (or subclinical) samples. At this time, cognitive therapy is best considered a promising, but as yet not adequately tested, intervention for the treatment of depression. PMID- 8473581 TI - Long-term sequelae of childhood sexual abuse: perceived family environment, psychopathology, and dissociation. AB - In this study, 105 abused and nonabused women were examined for patterns of adult psychopathology associated with childhood sexual abuse and to test the extent to which these patterns are independent of other pathogenic properties of the family environment. Clinical and nonclinical Ss completed the Family Environment Scale, the Minnesota Multiphasic Personality Inventory (MMPI), the Rorschach, and the Stanford Hypnotic Susceptibility Scale. Greater nonspecific impairment among abused women may be a consequence, at least in part, of pathogenic family structure rather than sexual abuse per se. However, MMPI and Rorschach responses suggest sexual abuse may render victims especially vulnerable to specific disturbances i involving soma and self. Abuse was associated with greater use of dissociation, but covariance analysis revealed this effect to be accounted for by family pathology. There was no evidence that sexual trauma is associated with hypnotizability. PMID- 8473582 TI - Sexual abuse, family environment, and psychological symptoms: on the validity of statistical control. AB - M. R. Nash, T. L. Hulsey, M. C. Sexton, T. L. Harralson, and W. Lambert (1993) reported on the effects of controlling for family environment when studying sexual abuse sequelae. Sexual abuse history was associated with elevated Minnesota Multiphasic Personality Inventory and Rorschach scores in a sample of 105 women, but many of the reported differences disappeared when a Family Functioning Scale score was used as a covariate. The present article considers the findings of Nash et al. in terms of the theoretical and statistical constraints placed on analysis of covariance and other partializing procedures. Because family dysfunction is not always causally antecedent to sexual abuse, and given the quasi-experimental quality of most abuse research, the use of covariate techniques to test hypotheses about the causal role of family environment in the impacts of sexual abuse may be ill advised. Analyses of a 2,964-subject data set illustrate these concerns. PMID- 8473583 TI - Culturally tailored HIV-AIDS risk-reduction messages targeted to African-American urban women: impact on risk sensitization and risk reduction. AB - African-American women recruited from low-income housing projects in Chicago (N = 106) were randomly assigned to view 1 of 3 20-min videotapes: a standard public health service tape on prevention of acquired immunodeficiency syndrome (AIDS), the same public health service tape but matching presenter and participant ethnicity and sex, or a tape that included the same content but was framed in a context specifically intended to increase cultural relevance. Participants who viewed the tapes presented by African-American women were significantly more sensitized to AIDS and were more likely to have discussed AIDS with friends, to be tested for human immunodeficiency virus (HIV) antibodies during the follow-up interval, and to request condoms at follow-up. These results support the use of culturally sensitive AIDS prevention messages targeted to specific populations, particularly to promote HIV-antibody testing. PMID- 8473584 TI - Group cognitive-behavioral therapy and group interpersonal psychotherapy for the nonpurging bulimic individual: a controlled comparison. AB - This study evaluated the effectiveness of group cognitive-behavioral treatment (CBT) and group interpersonal psychotherapy (IPT) for binge eating. Fifty-six women with nonpurging bulimia were randomly assigned to 1 of 3 groups: CBT, IPT, or a wait-list control (WL). Treatment was administered in small groups that met for 16 weekly sessions. At posttreatment, both group CBT and group IPT treatment conditions showed significant improvement in reducing binge eating, whereas the WL condition did not. Binge eating remained significantly below baseline levels for both treatment conditions at 6-month and 1-year follow-ups. These data support the central role of both eating behavior and interpersonal factors in the understanding and treatment of bulimia. PMID- 8473585 TI - Comparing the process in psychodynamic and cognitive-behavioral therapies. AB - Archival records were used to compare the therapy process in 30 brief psychodynamic and 32 cognitive-behavioral therapies. Verbatim transcripts of 186 treatment sessions were rated with the Psychotherapy Process Q-set, designed to provide a standard language for the description of process. Results demonstrated that although some features were common to both treatments, there were important differences. Cognitive-behavioral therapy promoted control of negative affect through the use of intellect and rationality combined with vigorous encouragement, support, and reassurance from therapists. In psychodynamic psychotherapies, there was an emphasis on the evocation of affect, on bringing troublesome feelings into awareness, and on integrating current difficulties with previous life experience, using the therapist-patient relationship as a change agent. The clinical theoretical precepts underlying psychodynamic treatments received considerable support. In cognitive-behavioral therapies, there was evidence for the importance of developmental, as opposed to rationalist, intervention strategies for treatment outcome. PMID- 8473586 TI - Peer drug associations and emotional restraint: causes or consequences of adolescents' drug use? AB - A 3-wave longitudinal design was used to examine the relationships among emotional restraint, peer drug associations, and gateway drug use in a sample of 1,256 middle school students. Structural equation modeling was used to compare 3 models: (a) One model viewed drug use as a consequence of emotional restraint and peer variables; (b) 1 viewed drug use as a cause of restraint and peer variables, and (c) 1 included reciprocal effects. All 3 models fit the data fairly well. However, the reciprocal model fit the data significantly better than either of the others. Within this model, low emotional restraint was significantly related to subsequent increases in gateway drug use among boys. In contrast, peer drug models and peer pressure were not related to subsequent changes in gateway drug use. Changes in peer drug models were, however, predicted by previous levels of gateway drug use. PMID- 8473587 TI - Children in homeless families: risks to mental health and development. AB - This study examined the psychological adjustment of 159 homeless children in comparison with a sample of 62 low-income children living at home. In each group, ages ranged from 8 to 17 years. As expected, homeless children were found to have greater recent stress exposure than housed poor children, as well as more disrupted schooling and friendships. Child behavior problems were above normative levels for homeless children, particularly for antisocial behavior. Across the 2 samples, however, behavior problems were more related to parental distress, cumulative risk status, and recent adversity than to housing status or income. Results suggest that homeless children share many of the risks and problems of other American children being reared in poverty. PMID- 8473588 TI - Expectancy challenge and drinking reduction: experimental evidence for a mediational process. AB - Substantial correlational evidence supports a causal (mediational) interpretation of alcohol expectancy operation, but definitive support requires a true experimental test. Thus, moderately to heavily drinking male college students were randomly assigned to 1 of 3 conditions in a pre-post design: Expectancy challenge (designed to manipulate expectancy levels), "traditional" information, and assessment-only control. Expectancy challenge produced significant drinking decreases, compared with the other 2 groups. Decreases in measured expectancies paralleled drinking decreases in the challenge condition. Significant increases in alcohol knowledge in the traditional program were not associated with decreased drinking. These experimental findings support a causal (mediational) interpretation of expectancy operation. The implications for a cognitive (memory) model of expectancies and for prevention and intervention programs for problem drinking and alcoholism are discussed. PMID- 8473589 TI - Stress exposure and stress generation in children of depressed mothers. AB - Two hypotheses were tested: (a) One mechanism contributing to the high rate of disorder in children of women with affective disorders is elevated exposure to stressful events and conditions and (b) the children of depressed women, particularly women with unipolar depression, contribute to event occurrence because of increased interpersonal conflict. Life stress interview assessments were made at 6-month intervals for 3 years on 53 children of unipolar, bipolar, medically ill, and normal women. Both hypotheses were confirmed. Transactional models of risk and further studies of the interpersonal functioning of children at risk for depression are needed. PMID- 8473590 TI - Final year dental students' views on cross-infection precautions. AB - This study was undertaken to determine the influence that undergraduate training currently has on the formation of clinical management strategies for minimizing cross-infection, among final year dental students. A 10-page questionnaire was sent to final year dental students attending 15 of the UK's 16 dental schools. A response rate of 60.5% was obtained. A large proportion of the students said they would be prepared to treat a known HBV carrier (90.4%) or HIV carrier (84.3%); a much higher proportion than has previously been found among qualified dental personnel. However, only 55.6% of the students agreed with current recommendations that they ought to adopt a universal cross-infection policy. Nevertheless, most students agreed with recommendations that they ought to wear gloves (96.6%), eye protection (84.3%) and a surgical mask (62.6%). Disparity between some responses suggested that some final year dental students might not have a fully thought out cross-infection strategy. PMID- 8473592 TI - Fracture strength of all-porcelain, resin-bonded bridges after testing in an artificial oral environment. AB - Twenty all-porcelain In-Ceram bridges were resin bonded to natural teeth on a study model. Ten of the test specimens were fixed on abutments placed directly in resin, and 10 were supported by an artificial periodontal membrane. Incisal forces of physiological magnitude and direction were applied in three bridges of both groups (test samples) in an artificial oral environment (1250,000 cycles). The fracture strength of the six test and 14 control specimens was tested in a universal testing instrument and the rupture strength measured. There was no significant difference between the fracture strength of the test and control samples. The artificial periodontal membrane around the abutment teeth did not reduce the fracture strength of the In-Ceram bridges. PMID- 8473591 TI - A comparison of the shear bond strengths to a resin composite of two conventional and two resin-modified glass polyalkenoate (ionomer) cements. AB - The inability of resin composite to bond directly to dentine has compromised the clinical success of this restorative material. This problem may be overcome by the so-called laminate technique in which glass polyalkenoate cement is placed upon dentine and then covered with a resin composite. The cement both adheres to dentine and affords micromechanical attachment to the composite. The introduction of the resin-modified glass polyalkenoate cements (RMCs) offers the potential for chemical union between cement and composite. This investigation examined the shear bond strengths of P-50 resin composite to four glass polyalkenoate lining materials, with and without the application of an intermediate bonding agent (Scotchbond 2). Two of the cements were RMCs (Vitrebond, XR-Ionomer) and the others were conventional base materials (Baseline, Ketac-Bond). The bond between P-50 and Vitrebond with or without Scotchbond 2 was significantly (P < 0.01) stronger and more consistent (P < 0.05) than that observed for all other materials. The treatment of the conventional materials and XR-Ionomer with Scotchbond 2 significantly (P < 0.01) improved the bond strengths to P-50. It is concluded that Vitrebond formed the most favourable cement-resin composite bond and that the other materials studied should be used in conjunction with an effective intermediate bonding agent, such as Scotchbond 2. PMID- 8473593 TI - Change in pH during setting of polyelectrolyte dental cements. AB - The change in pH during setting has been studied for five different glass polyalkenoate (ionomer) cements and for two different zinc polycarboxylate cements using a flat-headed combination electrode on both the fresh cement and on a slurry of the set cement. The results show that the pH of the glass ionomers was slightly lower in the early stages of setting than was the pH of the zinc polycarboxylates and also that the pH of glass ionomers rises more slowly. For anhydrous cements (i.e. those formulated from dried polymer) pH was found to rise quicker than for hydrous cements (i.e. those prepared from aqueous solutions of polymer). Previous workers have assumed that anhydrous cements undergo slower rises in pH than hydrous ones. Our results clearly refute this assumption, and also suggest that the reported pulpal irritation associated with the use of anhydrous glass ionomers may be due to something other than low pH. PMID- 8473594 TI - Durability of restorations in primary molars. AB - Techniques used to restore carious primary molars have changed over the past decade as new adhesive materials have been developed. The most meaningful way of assessing the efficacy of a technique is by clinical trials. This article reviews the information concerning amalgam, composite and glass polyalkenoate (ionomer) cement as well as extracoronal restorations. Stainless steel/nickel chrome crowns provide the most durable restoration, often surviving until the tooth exfoliates. Class II amalgam restorations, whilst being prone to fracture, have been shown to survive about 3 years, a figure that improves with increasing age of the child and the use of local anaesthesia. Over the shorter term resin-based composites appear to be at least as durable as amalgam, particularly with respect to the maintenance of a good anatomical form. In contrast, when assessed at 6 years the failure rate of composite restorations is high, 62%, whereas the failure rate of amalgam restorations at 5 years is as low as 20%. Glass ionomer cements and cermets are alternative materials for use in the primary dentition. The reported success rate of 33% over 5 years for conventional glass ionomer cements is encouraging, however cermets appear to be less successful but have not been evaluated over the longer term. Glass ionomer cements provide a means of restoring primary molars with minimal amount of destruction of sound tooth tissue and reduced treatment time for the young patient, whilst the local fluoride release is also a potential advantage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473595 TI - Three-year follow-up of five posterior composites: in vivo wear. AB - The wear of five posterior composites at occlusal contact areas (OCA) and contact free occlusal areas (CFOA) was evaluated in Class II cavities over a 3-year period with an accurate 3D-measuring technique. A clinical evaluation was also performed. The ultrafine compact-filled composites (Willems et al., 1992) showed acceptable OCA-wear rates ranging from 110 to 149 microns after 3 years. This is very similar to the OCA-wear rate of human enamel on molars, which is about 122 microns after 3 years. The fine compact-filled composite had an unacceptable OCA wear value of 242 microns after 3 years. The ultrafine midway-filled composite showed an exceptionally high CFOA-wear value of 151 microns after 3 years, which gave the impression of it being gradually washed out of the cavity. Clinically, 70% of the restorations made with the ultrafine midway-filled composite showed excellent colour match after 3 years. For most of the compact-filled composites slightly opaque fillings were noted and 63% of the restorations made with one of these materials were clearly opaque. It can be concluded that the investigated ultrafine compact-filled composites can be considered as amalgam alternatives as far as their wear resistance is concerned. PMID- 8473596 TI - Three-year follow-up of five posterior composites: SEM study of differential wear. AB - Assessing the wear of both enamel and composite at a shared occlusal contact area offers the opportunity to determine the differential wear between enamel and composite on the same tooth. Differential wear measurements were carried out on five posterior composite materials with an accurate 3D-measuring technique. The distinct wear step between enamel and composite was visualized by means of scanning electron photomicrographs. Both investigated ultrafine midway-filled and fine compact-filled composites (Willems et al., 1992a) have a considerably higher differential wear value and are, therefore, less suitable for rehabilitation of posterior teeth than are the ultrafine compact-filled composites, which have, in this study, a very satisfactory differential wear rate and appear to be highly wear resistant materials suitable for use in stress-bearing areas. PMID- 8473597 TI - A SEM study of denture plaque and oral mucosa of denture-related stomatitis. AB - The aim of this study was to compare the morphology of denture plaque and adjacent palatal mucosa in five subjects with denture-related stomatitis and a control group of five healthy subjects. Scanning electron microscope examination of copper plate replicas, which preliminary studies established were superior to epoxy resin replicas, showed that there were no consistent differences between the morphology of denture plaque and adjacent mucosa in the denture-related stomatitis group and control group. In each, the surface of the denture plaque was composed predominantly of coccoid- and rod-shaped bacteria with only some yeast cells. The mucosa was largely devoid of microorganisms and individual epithelial cells were shedding from its surface. PMID- 8473598 TI - Copper plate replica SEM of developing dental plaque in monkeys (Macaca fascicularis). AB - The aim of the study was to examine the development of dental plaque in macaque monkeys (Macaca fascicularis). Copper plate replicas were constructed from impressions of the labial surface of one of the upper central incisor teeth after tooth cleaning and when plaque had accumulated for 12, 24 and 48 h in each of five animals. Scanning electron microscope examination of the replicas showed that bacteria were present on the tooth surface as scattered individual cells, which after 24 h had formed a continuous layer. Both coccoid and filamentous bacteria were visible in 48-hour-old plaque. Such a rapid accumulation of potentially periodontopathic dental plaque emphasizes the importance of regular and meticulous oral hygiene. PMID- 8473599 TI - Assessing dental patients for their risk of being carriers of a blood-borne virus: the views of final year dental students. AB - A questionnaire was sent to final year dental students in all but one of the dental schools in the UK in 1991. The response was 447 out of 739 (60.5%). The students were asked about how they intended to approach various aspects of patient care once they were qualified and in practice. Almost half (44%) said they would use a cross-infection policy in which precautions would be stepped up for 'risky' patients. This study was undertaken to determine what they think are factors which might identify a patient who is infected, or at risk of being infected, by either hepatitis B virus or the human immunodeficiency virus. Those who said they would take personal histories to determine a patient's risk (30%) seemed prepared to ask about experiences which have relatively low predictive value for infection (e.g. blood transfusions), yet are reluctant to ask more pertinent questions, i.e. those concerning sexual activity. Those who would attempt to assess patients' risk status without asking 'intrusive questions' (14%) seem to have differing views about what sort of observable factors would be useful in framing such an assessment. PMID- 8473600 TI - Control of insecticide resistance in laboratory populations of house fly (Diptera: Muscidae) by introduction of susceptibility genes. AB - We investigated the effects of immigration of individuals carrying susceptibility alleles on the level of resistance in populations of the house fly, Musca domestica L., selected for malathion resistance. Two types of males, WHO/IN males (homozygous for susceptibility genes) and A14-WHO males (heterozygous for the second chromosome) were released into the resistant populations in 1:9, 1:1, and 9:1 ratios of immigrant/resident males. In both experiments, we observed that increasing the ratio of immigrant to resident males from 1:9 to 9:1 caused an associated increase in mortality caused by malathion applications. Release of A14 WHO males was more effective in stopping the evolution of resistance in resistant populations than was release of WHO/IN males. Fitness parameters of resistant and susceptible strains were also compared. The WHO/IN strain had low viability and fecundity. R and A14-WHO males were longer-lived compared with WHO/IN males, although they did not differ in mating success. PMID- 8473601 TI - Biochemistry and genetics of thiodicarb resistance in the house fly (Diptera: Muscidae). AB - The biochemistry and genetics of thiodicarb resistance were studied in the house fly, Musca domestica L. Bioassays with several strains revealed that a thiodicarb resistant strain was also resistant to carbaryl and to several organophosphates. Bioassays with a thiodicarb-synergist combination showed that resistance was only partially blocked by use of a synergist, suggesting the presence of target site resistance. The inheritance of resistance to thiodicarb was studied through crosses of the resistant parent to a multimutant, susceptible strain. Bioassays of backcrosses and the F2 generation showed that the major gene(s) conferring resistance to thiodicarb were on chromosome II. Cholinesterase assays showed that the enzyme of the resistant strain was several times more resistant to inhibition by carbamates than the enzyme of a susceptible strain or a strain with only metabolic resistance to insecticides. The data indicate that resistance to thiodicarb in the house fly was mainly because of target site changes. In addition, metabolism may contribute to resistance. PMID- 8473602 TI - An insert earphone system for delivery of spectrally shaped signals for physiological studies. AB - Acoustic signals arriving at the eardrum in free-space carry directionally dependent temporal and spectral information resulting from the acoustical effects of the body, head, and external ear as well as from differences in the length of the sound path to each ear. Through analysis of the responses of single auditory neurons, the acoustical and neural mechanisms by which sounds in free-space are localized are being studied. The approach involves simulation of free-field signals at the two eardrums of a cat via earphones and a study of the neuronal responses to such a virtual acoustic space. This approach makes it possible to manipulate different stimulus parameters independently in order to examine their role in determining the spatial characteristics of neuronal response. This report describes an insert earphone system designed for the delivery of such simulated signals which are broadband transients having complex spectra that mimic the acoustic transfer function of the external ear for frequency components up to 30 kHz or more. PMID- 8473603 TI - Analyses of Mossbauer mechanical measurements indicate that the cochlea is mechanically active. AB - Using the results of Mossbauer measurements, mechanical activity in the cochlea was tested for by comparing the measured basilar membrane (BM) transverse velocity amplitude with that calculated for a lossless mechanically passive system, derived from the measured BM velocity phase. If the cochlea is considered to be a lossless mechanically passive system, then the transverse velocity amplitude can be calculated from the group velocity and the relative variation of stiffness along the BM. The group velocity can be derived from the Mossbauer phase measurements, and the relative variation of stiffness along the BM can be derived from the frequency map of the cochlea. Making some general assumptions, the actual transverse velocity amplitudes are then compared from the Mossbauer amplitude data with those derived from the Mossbauer phase data, to determine if there is a significant transverse velocity gain. This operation was performed on several sets of Mossbauer data. From Mossbauer data showing sharp tuning, differences were found of up to 40 dB between the actual transverse velocity amplitude and the calculated lossless passive transverse velocity amplitude derived from the phase data. Examination of the assumptions made during the calculation of the lossless passive transverse velocity amplitude showed that none could account for a 40-dB transverse velocity gain. Thus, it is concluded that this transverse velocity gain can only be accounted for by the contribution to the amplitude of the transverse BM velocity by mechanically active elements along the cochlear duct. From Mossbauer data showing much less sharp tuning, it was found that the actual transverse velocity amplitude was approximately equal to the calculated lossless passive transverse velocity amplitude, basal to the characteristic place. This result is attributed to the disabling of the mechanically active elements along the cochlear duct. Apical to the characteristic place, the actual transverse velocity amplitude is shown to behave in a manner that suggests that the effective damping increases markedly in this region. This increase in effective damping is not necessarily due to an increase in viscous damping but could be due to any mechanism removing energy from the BM traveling wave. As an example, this paper discusses how this effective damping could be accounted for the transfer of energy to another mode of vibration at the characteristic place. PMID- 8473604 TI - A life-sized physical model of the human cochlea with optical holographic readout. AB - A life-sized physical model of the human cochlea is demonstrated. The model consists of two fluid-filled chambers separated by a polymer membrane and connected through a small hole that serves the same functional purpose as the helicotrema. The dimensions of the two chambers were made identical to those of scala vestibuli and scala tympani in the real cochlea. The membrane's width and length are the same as the values measured for the biological basilar membranes, and its thickness is chosen to give it appropriate rigidity. A piezoelectric transducer drives the system via an elastic window (acting as the oval window) on one side of the scala vestibuli. The resulting vibration pattern on the basilar membrane is investigated with an optical novelty filter, with detection sensitivity of 0.3 A at 2 kHz with a 1-Hz bandwidth. The overall response of this model is found to be a good extrapolation of Bekesy's low-frequency data. However, the tuning curves of this model are not as sharp as those found by Rhode, Johnstone, and others from the in vivo measurements. Possible implications of these results are discussed. PMID- 8473605 TI - Temporary threshold and loudness shifts: frequency patterns and correlations. AB - Two experiments studied the frequency pattern of TLS (temporary loudness shift) as a function of the level and frequency of the fatiguing sound. In experiment 1, the fatiguing tones were intermittent 375-, 1500-, or 3000-Hz tones (10 s on/10 s off) at 75, 80, 85, 90, or 95 dB SPL. The TLS patterns were established for a continuous, 60-phon test tone at different frequencies presented simultaneously with the intermittent fatiguing tone. In experiment 2, a 1000-Hz exposure tone with an intermittency of 10 s on/20 s off was used with a continuous 60-dB test tone at different frequencies. In both experiments, the total exposure duration was 60 s; TLS was measured 5 s after the exposure ended. For the lowest two exposure levels, the TLS pattern had one peak centered on the exposure frequency. As the exposure level increased, a two-peak pattern became evident, with the second peak at higher test frequencies. This finding could be interpreted as psychoacoustical evidence for the double (passive and active) mode of displacement of the basilar membrane. In experiment 2, a TTS (temporary threshold shift) measurement after exposure to a 45-min, 1000-Hz tone at 90 dB was added to the TLS sessions. The correlations between maximum TTS after a 45-min exposure and the TLS obtained after a 60-s exposure were calculated for each of the exposure levels and test frequencies used in TLS measurements. The correlation reached as high as 0.9 for TLSs measured at 1120 Hz after a 90-dB exposure; it was smaller but significant for TLSs at the exposure frequency. Despite these correlations, differences in the overall patterns of TTS and TLS suggest that they stem from two different mechanisms. PMID- 8473606 TI - Effects of varying signal and noise levels on pure-tone frequency discrimination in humans and monkeys. AB - This study examined the effects of presenting various signal and noise levels on pure-tone frequency difference limens (FDLs) in humans and monkey. Signal levels for two frequencies of 500 Hz and 4 kHz were varied both in quiet and in noise. For the lower frequency of 500 Hz, the two species exhibited qualitatively divergent FDLs as level increased in quiet: FDLs decreased at high levels for humans, but increased for monkeys. In noise, differences between human and monkey FDLs were less pronounced. At 500 Hz, monkeys exhibited slightly lower FDLs in noise than in quiet. At the higher frequency of 4 kHz, under all conditions, FDLs for both species were qualitatively similar. Results are discussed in relation to (1) different use of "temporal" coding mechanisms by humans and monkeys at 500 Hz, and (2) similar use of "rate-place" coding mechanisms at 4 kHz. PMID- 8473607 TI - Effects of varying signal duration on pure-tone frequency discrimination in humans and monkeys. AB - This study examined the effects of varying signal duration and pulse repetition rate on pure tone frequency difference limens (FDLs) at 500 Hz and 4 kHz in humans and monkeys. Two experiments examined FDLs as a function of tone duration from 12-400 ms, using stimuli presented either with a constant pulse rate, or with a constant interstimulus interval. In both cases, at 500 Hz, human FDLs increased more than monkey FDLs as duration decreased from 400 to 12 ms. This effect resulted in monkey FDLs that were about 14 times larger than human FDLs at 400 ms, but only about 4 times larger at 12 ms. At 4 kHz, human and monkey FDLs showed more similar rates of increase as duration decreased. A third experiment examined FDLs at 500 Hz for a 100-ms tone as a function of pulse rate (1 per 250 2000 ms). Here, FDLs for humans and monkeys varied in a similar fashion, indicating that both species' sensitivity was similarly affected by manipulating temporal variables relating to memory load, rather than sensory coding. These data provide evidence that, at 500 Hz, humans have a qualitatively different pure tone frequency analyzing mechanism from monkeys, possibly based on better access to phase-locking mechanisms. PMID- 8473608 TI - Effect of spectral envelope smearing on speech reception. II. AB - This paper describes two experiments on the effect of reduced spectral contrast on the speech-reception threshold (SRT) for sentences in a background of interfering sound. Signal processing is performed by smoothing the envelope of the squared short-time fast Fourier transform by a convolution with a Gaussian shaped filter, and overlapping additions to reconstruct a continuous signal. In the first experiment the effect of reduced spectral contrast on the SRT for male speech is investigated and compared with previously obtained results for female speech [ter Keurs et al., J. Acoust. Soc. Am. 91, 2872-2880 (1992)]. Spectral energy is smeared over bandwidths of 1/8, 1/4, 1/3, 1/2, 1, 2, and 4 oct. The results show that, despite the differences in spectral pattern between male and female voices, the SRT in noise increases similarly for both voices for smearing bandwidths over 1/3 oct. In terms of the ripple density of the spectral envelope the results indicate that the range of lower spectral modulations, up to a limit of about 1.5 periods/oct, is sufficient for the intelligibility of speech in interfering sounds. In the second experiment the extent of the threshold difference between a speech masker and a noise masker is investigated for spectral smearing bandwidths of 1/2, 1, and 2 oct. The release from masking found for the speech masker relative to the (steady-state) noise masker decreases with spectral envelope smearing. PMID- 8473609 TI - Acoustic image representation of a point target in the bat Eptesicus fuscus: evidence for sensitivity to echo phase in bat sonar. AB - Echolocating bats, Eptesicus fuscus, were trained in two distinct behavioral tasks to investigate the images they perceive of a sonar point target. In the first task, bats were trained in a two-alternative forced-choice procedure to detect electronically simulated target echoes at a range of approximately 57 cm. Half of the trials in the detection task contained echoes from a stationary target (simulated by a fixed echo delay) and half contained echoes from a jittering target (simulated by an echo delay alternating between two time values over successive sonar emissions). In the second task, bats were trained in a two alternative forced-choice procedure to discriminate between electronically simulated stationary and jittering targets, centered about a range of 57 cm. Both target detection and target jitter discrimination performance were assessed as a function of jitter magnitude, with jitter values ranging from 0-60 microseconds (corresponding to a change in distance of 0 to 10.3 mm). In both detection and discrimination tasks, the bat's performance changed cyclically with the magnitude of echo jitter. Specifically, when the phase of the playback echoes was unchanged, performance levels were poorest at 0 and 30 microseconds, and when the phase of the echoes alternated by 180 deg from one to the next, performance levels were poorest at 15 and 40-50 microseconds. The results suggest that Eptesicus is sensitive to the phase reversal of echoes and thus have implications for assessing receiver models of echolocation. PMID- 8473610 TI - Detection of temporal gaps in sinusoids: effects of frequency and level. AB - Thresholds for the detection of gaps in sinusoidal signals were measured as a function of frequency (100-2000 Hz) and level (25-85 dB SPL) in 11 normally hearing subjects. The sinusoids were presented in a background noise intended to mask spectral splatter associated with the gap. In a separate experiment, auditory filter shapes and detection efficiency were estimated for the same 11 subjects using the notched-noise method, at center frequencies of 100, 200, 400, and 800 Hz. Gap thresholds varied only slightly with frequency over the range 400 2000 Hz, but increased markedly at 200 and 100 Hz. At all center frequencies, gap thresholds were almost invariant with level for levels above 55 dB SPL. Gap thresholds increased at low levels, reaching values about 50% greater than their asymptotic values at a sensation level of about 20 dB. The decrease in auditory filter bandwidth with decreasing center frequency does not seem sufficient to account for the increase in gap thresholds. Also, individual gap thresholds at a given center frequency were not significantly correlated with the bandwidth of the auditory filter at that center frequency, as would be expected if the auditory filter played a role in limiting gap detection. Detection efficiency decreased with decreasing center frequency. Individual differences in detection efficiency were significantly correlated with gap thresholds. However, changes in detection efficiency with frequency do not seem to be of the right form to account for the increase in gap thresholds at low frequencies. It seems likely that there is a central sliding temporal integrator which integrates over longer times at lower center frequencies. PMID- 8473611 TI - Detecting temporal asynchrony with asynchronous standards. AB - The ability of listeners to detect asynchrony in either the temporal onset or offset of individual components in a multicomponent complex was investigated. A standard stimulus was created having a simple kind of asynchrony by linearly delaying successive components of a complex stimulus. Additional asynchrony (the signal) was created by altering the temporal position of a single component of the complex relative to its temporal position in the standard. Asynchrony discrimination was measured for harmonic signals (experiment I) and for complexes in which the components were logarithmically spaced in frequency (experiment II). For the onset condition, asynchrony in either the harmonic or logarithmic complex greatly increased the difficulty in detecting the temporal asynchrony of a single component. For the offset condition, asynchrony discrimination was not greatly affected by asynchrony in the standard. PMID- 8473612 TI - Extracting dynamic parameters from speech movement data. AB - A quantitative characterization of articulatory movements, using the parameter values of a linear second-order dynamical system, was developed in order to compare classes of movements, in particular, classes defined by linguistic factors such as syllable position, stress, and vowel quality. Movements of the lower lip in utterances such as ['bibebib] and [babe'bab] were partitioned into sections ("windows") in two ways: at successive displacement peaks and valleys, and at the right edge of plateau regions around such extreme values. The linguistic factors affected natural frequency in similar ways regardless of whether damping ratio was permitted to vary or held fixed at one of several different values. Damping ratio was generally unaffected by the linguistic factors. For the most part, the type of partition or window did not affect the patterns of the results, with the exception of the closing gesture out of the reduced syllable. PMID- 8473613 TI - Production and perception of a novel, second-language phonetic contrast. AB - Four experiments, all of which focused on vowel duration, assessed Chinese subjects' production and perception of the contrast between /t/ and /d/ in the final position of English words. Vowel duration was measured in minimal pairs in the first experiment. The stimuli in natural-edited beat-bead and bat-bad continua in which vowel duration varied in 20-ms steps were then presented to native English and Chinese subjects in a forced-choice test, in an experiment using the method of adjustment, and in an imitation task. The non-natives who learned English in childhood closely resembled native speakers in all four experiments. Three groups of non-natives who had learned English as a second language in adulthood, on the other hand, differed from the native speakers. The late learners produced significantly longer vowels in words ending in /d/ than /t/. However, the late learners' vowel duration differences were much smaller than the native speakers', and were correlated significantly with degree of foreign accent in English. The late learners differed from the native speakers in several ways in the two perception experiments, and also in the imitation task. The pattern of significant and nonsignificant between-group differences, but not data for individual subjects, was consistent with the hypothesis that L2 (second language) production accuracy is limited by the adequacy of perceptual representations for sounds in the L2. PMID- 8473614 TI - Comment on "Temporal modulation transfer functions in patients with cochlear implants" [J. Acoust. Soc. Am. 91,2156-2164 (1992)]. PMID- 8473615 TI - Ratio of variance to mean of action potential counts for an auditory nerve fiber model with second-order refractory behavior. AB - Sequences of interval times were generated with the first- and second-order interval probability dependence proposed by Gaumond et al. [J. Neurophysiol. 48, 856-873 (1982)] to characterize cochlear nerve fiber spontaneous action potential (AP) sequences. The ratio F(T) of the variance to the mean of the count of APs in bins of T s was computed for the simulated sequences, and compared to the corresponding measure for cochlear nerve fiber data presented by Lowen and Teich [J. Acoust. Soc. Am. 92, 803-806 (1992)]. The simulations were generally consistent with the data in the range 15 < T < 100 ms. PMID- 8473616 TI - Alteration of central auditory processing of brief stimuli: a review and a neural model. AB - There is evidence that the manner in which the central auditory system processes transient signals can be altered by either of two seemingly unrelated experimental factors, namely, hearing loss, or the presence of a continuous tone of moderate intensity. In particular, altered processing of brief signals in the central auditory system is indicated by either: (i) lower (better) behaviorally measured thresholds for pulsate electrical stimulation of brain-stem auditory nuclei, or (ii) an increased amplitude of some components of the brain stem or cortical potentials evoked by brief acoustic stimuli. A simple two-neuron model which evolved from the above findings and related visual system phenomena was used to evaluate the effects produced by hearing loss or continuous tone. In the model, a "hearing loss" condition, which was represented by less spontaneous neural activity (and, hence, reduced inhibition) relative to a "normal hearing" condition, yielded both increased gain for steady-state stimuli and increased responsiveness for transient stimuli. Thus the model provides two possible, and simultaneously operable, explanations of reduced electrical stimulation thresholds and increased evoked potential amplitude: one based on increased steady-state gain and the other based on increased responsiveness to transient stimuli. A third condition, "normal hearing with a longer excitatory time constant," yielded effects that were similar to those produced by reduced inhibition, thereby suggesting a physiological basis for alteration of psychophysically measured time constants. PMID- 8473617 TI - Otoacoustic emissions from normal-hearing and hearing-impaired subjects: distortion product responses. AB - Distortion product otoacoustic emissions (DPOAE) were measured in normal-hearing and hearing-impaired human subjects. Analyses based on decision theory were used to evaluate DPOAE test performance. Specifically, relative operating characteristic (ROC) curves were constructed and the areas under these curves were used to estimate the extent to which normal and impaired ears could be correctly identified by these measures. DPOAE amplitude and DPOAE/noise measurements were able to distinguish between normal and impaired subjects at 4000, 8000, and, to a lesser extent, at 2000 Hz. The ability of these measures to distinguish between groups decreased, however, as frequency and audiometric criterion used to separate normal and hearing-impaired ears decreased. At 500 Hz, performance was no better than chance, regardless of the audiometric criterion for normal hearing. Cumulative distributions of misses (hearing-impaired ears incorrectly identified as normal hearing) and false alarms (normal-hearing ears identified as hearing impaired) were constructed and used to evaluate test performance for a range of hit rates (i.e., the percentage of correctly identified hearing-impaired ears). Depending on the desired hit rate, criterion values of -5 to -12 dB SPL for DPOAE amplitudes and 8 to 15 dB for DPOAE/noise accurately distinguished normal-hearing ears from those with thresholds greater than 20 dB HL for the two frequencies at which performance was best (4000 and 8000 Hz). It would appear that DPOAE measurements can be used to accurately identify the presence of high-frequency hearing loss, but are not accurate predictors of hearing status at lower frequencies, at least for the conditions of the present measurements. PMID- 8473618 TI - Intermodulation distortion (F2-F1) in inner hair cell and basilar membrane responses. AB - Round window (RW) recordings in guinea pigs show a large response at the frequency of the quadratic difference tone (QDT) at F2-F1 for high-frequency (> 8 kHz) tone pairs. The magnitude of the RW response is dependent on frequency and level of the primaries. The QDT cochlear microphonic produced is largest for primaries with a frequency separation of approximately 900 Hz. Its source is probably the local activity of hair cells in basal cochlear locations where the high-frequency tones interact. QDT measurements from locations inside the organ of Corti show that the magnitude of the QDT is largest in the inner hair cell (IHC) region and monotonically increases as the difference in the frequency of the primaries decreases. Measured as IHC intracellular ac receptor potential, the QDT appears to be the result of a mechanical stimulus to the cell rather than as an inherent property of the nonlinear transduction in the IHC. However, QDT of the same form is not evident in the velocity responses of the basilar membrane. These results suggest that the outer hair cells (OHC) produce a strong quadratic distortion product mechanical force to stimulate inner hair cells. This mechanical drive may not be present, or is a weak component, in basilar membrane motion. PMID- 8473619 TI - A comparison of N1 of the whole nerve action potential and wave i of the brain stem auditory evoked response in Mongolian gerbil. AB - The present study seeks to provide empirical support for the assumption that wave i of the gerbil brain-stem auditory evoked response (BAER) corresponds to N1 of the whole nerve action potential (WNAP) by comparing the latency and amplitude of BAER wave i and WNAP N1. Fourteen 3-month old gerbils were anesthetized with Nembutal and Urethane-Dial. Normothermia was maintained by a homeothermic blanket system. BAERs were recorded with Grass needle electrodes placed subdermally. The WNAP was recorded with a silver wire placed in the round window niche. WNAP and BAER were simultaneously recorded with a passband of 100-10,000 Hz. Responses consisted of 500 sweeps, and two responses were obtained for each condition. Clicks were 25-microseconds electrical pulses. Tonebursts were shaped with a Hanning window, with 1-ms rise and fall times. Toneburst frequencies included 1, 2, 4, 8, and 16 kHz. For each stimulus, responses were obtained at levels of 30, 50, 70, and 90 dB pSPL. SPL was measured near the entrance to the ear canal with an Etymotic ER-7C probe microphone. Dependent variables were the latency and amplitude of N1 of the WNAP and wave i of the BAER. The latencies of wave i and N1 were very similar. Mean (across animal) latencies of N1 and wave i were within 70 microseconds for all six stimuli (clicks, tonebursts) and all four levels. Latency/intensity function slopes for N1 and wave i were also very similar, with both dependent variables showing an increasing latency/intensity function slope with decreasing toneburst frequency. The N1/wave i amplitude ratio was computed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473620 TI - Binaural maximum length sequence auditory-evoked brain-stem responses in human adults. AB - This study compared monaural and binaural maximum length sequence auditory-evoked brain-stem responses (MLS ABRs) in normal hearing adults. The first experiment demonstrated that reliable binaural MLS ABRs could be recorded which were essentially the same as those recorded monaurally. The second experiment generalized this finding by assessing a range of intensities including threshold stimuli. ABR thresholds, wave V latency x intensity and amplitude x intensity functions, wave V latency and amplitude reproducibility, and waveform reproducibility were comparable for the monaural and binaural MLS ABRs with some minor qualifications. In the third experiment, comparability of monaural and binaural MLS ABRs was generalized to a range of rates from those used conventionally to rates far faster than possible with signal averaging. Again, there was little difference between the binaural and monaural MLS ABRs over the range of rates assessed. PMID- 8473621 TI - Audiometric and histological differences between the effects of continuous and impulsive noise exposures. AB - An experiment was designed to determine if, for equal SPL and power spectrum, the effects on hearing of high-kurtosis noise exposures and a Gaussian noise exposure are different and the extent to which any differences measured in terms of audiometric and histological variables are frequency specific. Three groups of chinchillas with 10 animals/group were exposed for 5 days at 90 dB SPL to one of three types of noise, each with the same power spectrum. The impulsiveness, defined by the kurtosis, and the region of the spectrum from which the impulsive components of the noise were created differed for two of the noises, while the third was a continuous Gaussian noise. The results show that the most impulsive noise produced up to 20 dB greater permanent threshold shift at the high frequencies than did the Gaussian noise exposure. However, these audiometric results were difficult to reconcile with the pattern of sensory cell losses that showed statistically significant larger losses of outer hair cells for the impulsive exposure in the 0.25-kHz region. When the impacts in a high-kurtosis noise were created from the energy in the 1- through 6-kHz region of the spectrum, the audiometric profile of hearing loss was similar to that produced by the Gaussian noise; however, inner hair cell losses were significantly greater in the 4-kHz octave band region of the cochlea. PMID- 8473622 TI - A maximum-likelihood method for estimating thresholds in a yes-no task. AB - A maximum-likelihood procedure for estimating threshold values in a yes-no task is presented. In computer simulations of this procedure, it is demonstrated that the variability of the threshold estimates is little affected by the density of the hypotheses tested for a fixed range, or by serious misestimates of the slope of the psychometric functions. The threshold value is also largely independent of the starting value of the signal. The standard deviation of the threshold estimates appears to decrease with the square root of the number of trials, with a 2- to 3-dB standard deviation possible if only 12 trials are used in the threshold estimates. Data are presented using human listeners tested on 5 days. Two threshold estimates, based on 12 trials, were made at each of the six audiometric frequencies on each day. The mean data appear sensible, and the standard deviation of the measured thresholds is about 3 dB. Using this procedure, it takes less than 3 min to measure the audiogram for a single ear. PMID- 8473623 TI - Comodulation masking release as a function of type of signal, gated or continuous masking, monaural or dichotic presentation of flanking bands, and center frequency. AB - Thresholds were measured for detecting a signal centered in a narrow-band noise (NBN) masker (on-frequency band, OFB), for the OFB alone, and with two flanking bands (FBs) added to the OFB, one centered above and one below the OFB. The FBs were either correlated with the OFB or were independent and were presented either to the same ear as the signal plus OFB (monaural condition) or to the opposite ear (dichotic condition). The OFB and FBs were either gated with the signal, or were presented continuously. Three signal types were used: a pure tone; an NBN uncorrelated with the OFB; and an NBN correlated with the OFB. The signal was centered at 0.5, 2, or 6 kHz. Comodulation masking release was estimated either as the difference between threshold with the OFB alone and with the OFB plus correlated FBs [CMR(R-C)], or as the difference between thresholds using correlated and uncorrelated FBs [CMR(U-C)]. Although there were marked individual differences, positive CMR(R-C) values were found in all conditions for all three signal types. CMR(U-C) values were often larger than those for CMR(R-C), reflecting the fact that the uncorrelated FBs tended to produce interference effects, especially for the gated maskers, and at 6 kHz. Values of CMR were larger and more consistent across subjects for continuous than for gated maskers. For continuous maskers, the values of CMR tended to be smallest for the correlated-NBN signal. Results are discussed in terms of available cues and in terms of perceptual grouping mechanisms. PMID- 8473624 TI - Source level discrimination by the lateral line system of the mottled sculpin, Cottus bairdi. AB - A conditioned feeding response of the mottled sculpin was used to measure level discrimination by the lateral line system as a function of source level, frequency, and distance. Level discrimination limens (LDLs) were determined with a 6-mm-diam, sinusoidally vibrating sphere placed in front of the trunk lateral line system at varying distances from the trunk of the fish. LDLs were relatively independent of frequency over most of the detection bandwidth, with mean values ranging from 5-6 dB from 10 to 50 Hz at a fish-to-source distance of 15 mm. The mean LDL at 100 Hz, near the upper end of the frequency range of the lateral line system was 8-9 dB at the same source distance. Mean LDLs at 10 and 20 dB above detection threshold were not significantly different, nor were mean LDLs at distances ranging from 7.5 to 30 mm for a 50-Hz, 10-dB SL source. The level encoding features of posterior lateral line fibers innervating the trunk were also determined from data previously collected under stimulus conditions nearly identical to those used for behavioral studies. Afferent fibers responded to level increments with increases in both spike rate and phase-locking over most of the conditions used in behavioral experiments. Although it was impossible to eliminate spike rate as a level-encoding mechanism at any stimulus condition, phase-locking appeared to be a strong candidate at low source levels and vibration frequencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473625 TI - Comparison of spectral and nonspectral frequency difference limens for human and nonhuman primates. AB - Difference limens for frequency were measured in normal-hearing human and nonhuman-primate (macaque) subjects. Stimuli were 1-kHz pure tones, containing both spectral and temporal cues, and 100-Hz sinusoidally amplitude modulated broadband noise (SAM noise), containing only temporal (nonspectral) cues. Subjects were tested for a minimum of 20 sessions and until difference limens were stable over time for each stimulus at each of several sensation levels. Difference limens for pure-tone stimuli showed almost no overlap between human and nonhuman-primate subjects. Difference limens for SAM-noise stimuli for human and nonhuman-primate subjects overlapped considerably. The correlations between performance for the pure-tone stimuli and performance for the SAM noise stimuli averaged 0.60. These data suggest that at least two factors influence pure-tone frequency discrimination. One factor is dependent on the presence of place mechanisms while the other factor, or group of factors, seems to influence both spectral and nonspectral frequency discrimination. PMID- 8473626 TI - Dichotic interference effects in gap detection. AB - Thresholds for detecting a temporal gap in a 20-Hz-wide band of noise (the target) were measured for the target alone, and in the presence of multiple 20-Hz wide flanking bands presented to the opposite ear. The flanking bands caused gap thresholds to increase, and this effect was greater at higher levels of the flanking bands. The impairment to gap detection was greater when the flanking bands were comodulated with the target (i.e., had the same envelope) than when they were not comodulated, except at very low and high levels of the flanking bands. A series of supplementary experiments was conducted to investigate why the difference between comodulated and noncomodulated bands was reduced at high levels. The results suggest that this was not due to inter-aural crosstalk. It may have been partly caused by: (1) a central masking effect that reduced the effective sensation level of the target band at high levels of the contralateral flanking bands; (2) reduced independence of the flanking bands owing to broadening of the auditory filters at high levels. The results are discussed in terms of perceptual grouping processes. PMID- 8473627 TI - Auditory and visual localization performance in a sequential discrimination task. AB - Four subjects were tested in a two-alternative, forced-choice, three down-one up adaptive paradigm in which two 200-ms signals were presented sequentially with a 200-ms interstimulus interval. The subject's task was to indicate whether the second stimulus was to the right or left of the first. Tests were conducted with 57 dB (A-weighted), 1.0-kHz high-pass noise, the minimum audible angle (MAA) task, and with lights emitting 620 nm at a luminance level of 200 mL, the minimum visible angle (MVA) task. Localization performance in the MAA task was equal to or better than that obtained in the MVA task for all regions of the frontal field with only one exception, presentations at 0 degrees azimuth. The implications of these results are discussed. PMID- 8473628 TI - Prewhitening for intelligibility gain in hearing aid arrays. AB - In this article, prewhitening multimicrophone data prior to use in an optimum spatial-filter preprocessor for a monaural hearing aid is considered. Considering preprocessor capabilities, interference signal spectral content and intelligibility, it is argued that prewhitening is advantageous. This advantage is illustrated via simulation of a head worn array. Also, an effective procedure for the design of (prewhitening) digital filters is presented. The effectiveness of this filter design technique is shown by presenting several prewhitening filter design examples. PMID- 8473629 TI - Speaking fundamental frequency, intensity, and rate of adventitiously profoundly hearing-impaired adult women. AB - No objective group data on speaking fundamental frequency (F0), intensity, or rate have been reported on the speech of adventitiously profoundly hearing impaired adult women. Results of the present study showed that F0 was significantly higher, intensity significantly greater, and speaking rate significantly slower for 12 adventitiously profoundly hearing-impaired adult women than for 20 normal-hearing control subjects of the same sex and approximate age. Based on these objective data, aural rehabilitation is recommended for the improvement and monitoring of speaking F0, intensity, and rate abnormalities in the adventitiously profoundly hearing impaired. PMID- 8473630 TI - FO gives voicing information even with unambiguous voice onset times. AB - The voiced/voiceless distinction for English utterance-initial stop consonants is primarily realized as differences in the voice onset time (VOT), which is largely signaled by the time between the stop burst and the onset of voicing. The voicing of stops has also been shown to affect the vowel's FO after release, with voiceless stops being associated with higher FO. When the VOT is ambiguous, these FO "perturbations" have been shown to affect voicing judgments. This is to be expected of what can be considered a redundant feature, that is, that it should carry a distinction in cases where the primary feature is neutralized. However, when the voicing judgments were made as quickly as possible, an inappropriate FO was found to slow response time even for unambiguous VOTs. This was true both of FO contours and level FO differences. These results reinforce the plausibility of tonogenesis, and they add further weight to the claim that listeners make full use of the signal given to them, even when overt labeling would seem to indicate otherwise. PMID- 8473631 TI - Adequacy of auditory models to predict human internal representation of speech sounds. AB - A long-standing question that arises when studying a particular auditory model is how to evaluate its performance. More precisely, it is of interest to evaluate to what extent the model representation can describe the actual human internal representation. Here, this question is addressed in the context of speech perception. That is, given a speech representation based on the auditory system, to what extent can it preserve phonetic information that is perceptually relevant? To answer this question, a diagnostic system has been developed that simulates the psychophysical procedure used in the standard Diagnostic-Rhyme Test (DRT). In the psychophysical procedure, the subject has all the cognitive information needed for the discrimination task, a priori. Hence, errors in discrimination are due mainly to inaccuracies in the auditory representation of the stimulus. In the simulation, the human observer is replaced by an array of recognizers, one for each pair of words in the DRT database. The recognizer used [Ghitza and Sondhi, J. Acoust. Soc. Am. Suppl. 1 87, S107 (1990)] was designed to keep errors due to the recognition procedure to a minimum, so that the overall detected errors are due mainly to inaccuracies in the front-end representation. The system provides detailed diagnostics that show the error distributions among six phonetically distinctive features. Results are given for the behavior of two speech analysis methods, a representation based on the auditory system and one based on the Fourier power spectrum, in quiet and in a noisy environment. These results are compared with psychophysical results for the same database. PMID- 8473632 TI - Passive acoustic localization of the Atlantic bottlenose dolphin using whistles and echolocation clicks. AB - A method for localization and tracking of calling marine mammals was tested under realistic field conditions that include noise, multipath, and arbitrarily located sensors. Experiments were performed in two locations using four and six hydrophones with captive Atlantic bottlenose dolphins (Tursiops truncatus). Acoustic signals from the animals were collected in the field using a digital acoustic data acquisition system. The data were then processed off-line to determine relative hydrophone positions and the animal locations. Accurate hydrophone position estimates are achieved by pinging sequentially from each hydrophone to all the others. A two-step least-squares algorithm is then used to determine sensor locations from the calibration data. Animal locations are determined by estimating the time differences of arrival of the dolphin signals at the different sensors. The peak of a matched filter output or the first cycle of the observed waveform is used to determine arrival time of an echolocation click. Cross correlation between hydrophones is used to determine inter-sensor time delays of whistles. Calculation of source location using the time difference of arrival measurements is done using a least-squares solution to minimize error. These preliminary experimental results based on a small set of data show that realistic trajectories for moving animals may be generated from consecutive location estimates. PMID- 8473633 TI - Multi-frequency transducer assembly for nonlinear ultrasonic measurements. PMID- 8473634 TI - Identification of extensive coronary artery disease in women by exercise single photon emission computed tomographic (SPECT) thallium imaging. AB - OBJECTIVES: The aim of this study was to examine the ability of exercise single photon emission computed tomographic (SPECT) thallium imaging to identify high risk women with left main or three-vessel coronary artery disease using a stepwise discriminant analysis. BACKGROUND: Previous studies have used statistical methods to identify high risk men with coronary artery disease. Only limited data are available in women. METHODS: Exercise SPECT thallium imaging and coronary arteriography were performed for evaluation of chest pain in 243 women. Group 1 comprised 58 women with left main or three-vessel coronary disease and group 2 comprised 185 women with no or one- or two-vessel disease. Stepwise discriminant analysis was used to determine predictors of left main or three vessel disease. RESULTS: On univariate analysis, women in group 1 were older (p < 0.03) and had a lower exercise work load (p < 0.02), lower exercise heart rate (p < 0.004), higher prevalence rate of diabetes mellitus (p < 0.0003) and more multivessel thallium abnormality (p < 0.0001) compared with women in group 2. On multivariate analysis, only multivessel thallium abnormality (F = 43) and exercise heart rate (F = 6) were independent predictors of left main or three vessel coronary disease. A model based on these two variables separated the women into three risk groups: 99 patients with 9%, 70 patients with 23% and 74 patients with 45% prevalence of left main or three-vessel disease (p < 0.0001). CONCLUSIONS: High risk women with left main or three-vessel coronary disease can be identified by exercise SPECT thallium imaging. PMID- 8473635 TI - Comparison in women versus men of composition of atherosclerotic plaques in native coronary arteries and in saphenous veins used as aortocoronary conduits. AB - OBJECTIVES: This study quantifies and compares the components of atherosclerotic plaques in native coronary arteries and in saphenous vein grafts used for aortocoronary bypass surgery in women versus those in men. BACKGROUND: Plaque composition has been described in various manifestations of fatal coronary artery disease and after the bypass operation, but no reports have investigated this composition according to gender. METHODS: A total of 979 5-mm segments of native coronary arteries and 842 5-mm segments of saphenous vein grafts were examined by computerized planimetric technique in 11 women and 11 men who were matched for survival time after the bypass operation. RESULTS: Comparison of the plaque components revealed that atherosclerotic plaques in women, compared with those in men, contained significantly more cellular fibrous tissue, both in native coronary arteries (mean 38% vs. 4%, p < 0.001) and in saphenous vein grafts (mean 70% vs. 36%, p < 0.05). In contrast, the proportion of dense fibrous tissue was significantly less in the atherosclerotic plaques of women than in those of men, both in native coronary arteries (mean 50% vs. 85%, p < 0.001) and in saphenous vein grafts (mean 25% vs. 57%, p < 0.05). CONCLUSIONS: Cellular fibrous tissue is often found at an early stage of plaque development, whereas dense fibrous tissue is a major component in later stages. Thus, the plaque composition of the native coronary arteries and saphenous venous conduits differed in men and women, with the plaques of the women appearing younger than those of the men. PMID- 8473636 TI - Sequential teboroxime imaging during and after balloon occlusion of a coronary artery. AB - OBJECTIVES: We sought to assess whether sequential teboroxime imaging can rapidly evaluate vessel patency and identify the coronary artery occluded in patients undergoing balloon occlusion of a coronary artery. BACKGROUND: Intravenous thrombolytic therapy results in successful reperfusion of the infarct-related artery in only 50% to 80% of cases. A noninvasive technique to serially evaluate coronary perfusion would identify patients who might benefit from other interventions such as emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or increased intensity of thrombolytic therapy. METHODS: Teboroxime scans were performed during balloon occlusion in 15 nonconsecutive patients undergoing angioplasty of a major coronary artery. Equivalent views were repeated after successful angioplasty. RESULTS: The mean time between balloon occlusion and reperfusion imaging was 1.6 +/- 0.6 h. The mean number of defects decreased significantly from 4.13 +/- 1.01 during balloon occlusion to 0.27 +/- 0.44 after reperfusion (p = 0.0006). There was a 30% decrease in the defect/normal zone count/pixel ratios during balloon occlusion and normalization of these ratios after reperfusion (p = 0.0006). The scans correctly identified all nine left anterior descending coronary artery occlusions and both right coronary artery occlusions. One of the four left circumflex coronary artery occlusions was incorrectly identified as a right coronary artery occlusion by scan criteria. Overall, the scans correctly identified the occluded artery 93% of the time (kappa = 0.88). The scan was 100% accurate for distinguishing occlusion of the left anterior descending coronary artery (n = 9) from occlusions of the left circumflex or right coronary artery (n = 6). CONCLUSIONS: We believe that this is the first clinical study to demonstrate that sequential planar imaging with teboroxime can 1) rapidly detect acute coronary artery occlusion and reperfusion, and 2) identify the occluded coronary artery. A trial comparing rapid sequential teboroxime imaging with coronary angiography in patients receiving thrombolytic therapy for acute myocardial infarction is warranted. PMID- 8473637 TI - The proper tool for the job. PMID- 8473638 TI - Adenosine thallium-201 is superior to exercise thallium-201 for detecting coronary artery disease in patients with left bundle branch block. AB - OBJECTIVES: We sought to assess the comparative diagnostic accuracy of adenosine versus exercise in conjunction with thallium-201 scintigraphy for the detection and localization of coronary artery disease in patients with left bundle branch block on the rest electrocardiogram (ECG). BACKGROUND: Patients with left bundle branch block on the rest ECG frequently have artifactual reversible septal perfusion defects on exercise thallium-201 scintigraphy. Adenosine thallium scintigraphy is a theoretically attractive alternative in these patients. METHODS: One hundred seventy-three consecutive patients with left bundle branch block were evaluated with either exercise thallium (n = 56) or adenosine thallium (n = 117) scintigraphy. The tomographic thallium images were interpreted visually with adjunctive quantitative analysis. Follow-up cardiac catheterization was performed in 31 of the 56 patients in the exercise thallium group and 42 of the 117 patients in the adenosine thallium group. RESULTS: Minor subjective side effects were noted in most patients in the adenosine thallium group (86%); atrioventricular block occurred in seven patients (6%). The overall predictive accuracy was 93% in the adenosine thallium group and 68% in the exercise thallium group (p = 0.01). The combined specificity for the detection of disease in the coronary arteries subtending the septum (the left anterior descending and right coronary arteries) was only 42% with exercise thallium scintigraphy versus 82% with adenosine thallium scintigraphy (p < 0.0002). CONCLUSIONS: Adenosine thallium imaging 1) was superior to exercise thallium imaging in the detection of coronary artery disease in patients with left bundle branch block; 2) obviated septal artifacts, thereby markedly improving the specificity in the left anterior descending and right coronary arteries; and 3) was safe in patients with left bundle branch block. PMID- 8473639 TI - Progression of coronary artery disease is dependent on anatomic location and diameter. The INTACT investigators. AB - OBJECTIVES: This study represents the first prospective, quantitative analysis of the association of progression of coronary atherosclerosis with anatomic site and diameter. BACKGROUND: The progressive course of coronary artery disease has been documented in many angiographic follow-up trials. METHODS: The data of 348 patients with coronary artery disease from the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) were reviewed. Standardized coronary angiograms were taken 3 years apart and were analyzed quantitatively. The coronary tree was subdivided into 25 segments. The progression of 1,063 preexisting coronary stenoses and the appearance of 247 newly formed stenoses was assessed in relation to the mean diameter of segments (< 2 mm, 2 to 3 mm, > 3 mm) and to their position in the coronary tree (proximal, mid, distal) and in the three major coronary arteries. RESULTS: Decreases in the minimal diameter of preexisting stenoses were largest in segments that were > 3 mm in diameter (mean +/- SD 0.23 +/- 0.5 mm vs. 0.10 +/- 0.4 mm and 0.02 +/- 0.3 mm, p < 0.001), in a proximal position (0.14 +/- 0.5 mm vs. 0.09 +/- 0.4 mm and 0.06 +/- 0.3 mm, p = 0.081) and in the right coronary artery (0.14 +/- 0.4 mm vs. 0.07 +/- 0.4 mm and 0.07 +/- 0.3 mm, p < 0.01). Changes in percent diameter stenosis of preexisting stenoses were lowest in segments that were < 2 mm in diameter and in a distal position (p = NS). The number of new stenoses/segment was lowest in segments that were < 2 mm in diameter (44 of 1,756 vs. 139 of 1,967 and 64 of 1,125, p < 0.001) and in a distal position (77 of 2,370 vs. 84 of 1,193 and 86 of 1,285, p < 0.001) and was highest in segments of the right coronary artery (100 of 1,546 vs. 66 of 1,496 and 72 of 1,492, p = 0.044). CONCLUSIONS: Progression of coronary artery disease occurs most frequently in coronary segments that are > 2 mm in diameter, in a proximal or midartery position and in the right coronary artery. PMID- 8473640 TI - Angina and persistent exercise thallium defects: independent risk factors in elective vascular surgery. AB - OBJECTIVES: In this study, we assessed the utility of exercise thallium-201 scintigraphy and other clinical factors in predicting perioperative cardiac complications in patients undergoing elective vascular surgery. BACKGROUND: The risk of cardiac complications among such patients is very high. METHODS: The study group comprised 116 men (mean age 67 years). Fifty patients (43%) had a history of coronary artery disease, including angina pectoris in 26 (22%), myocardial infarction in 32 (28%) and coronary artery bypass surgery in 19 (16%). RESULTS: There were a total of 22 perioperative myocardial infarctions (18.9%), including 2 cardiac deaths (1.7%). A significantly greater proportion (p < 0.05) of patients with than without perioperative complications had a history of coronary artery disease (77% vs. 35%), angina (59% vs. 14%), prior myocardial infarction (50% vs. 22%), abnormal electrocardiogram (68% vs. 40%) and abnormal exercise thallium test (75% vs. 47%). The patient group with complications also had a significantly lower mean rest ejection fraction (45 +/- 3% vs. 55 +/- 2%, p < 0.005). Independent predictors of complication, as determined by straight logistic regression, were angina and fixed thallium defects after exercise. CONCLUSIONS: Our data indicate that angina and the presence of fixed thallium defects after exercise are independent predictors of cardiac risk in patients undergoing elective vascular surgery. These findings are compatible with other studies showing that nonredistribution on standard 3- to 4-h delayed studies cannot exclude viable myocardium at risk. PMID- 8473641 TI - Assessment of perioperative risk: have we put the cart before the horse. PMID- 8473642 TI - Isovolumetric relaxation flow in patients with ischemic heart disease. AB - OBJECTIVES: The purpose of this study was to clarify the characteristics of flow during the isovolumetric relaxation period and to analyze the relation between these flow patterns and standard hemodynamic indexes. BACKGROUND: Outward motion of the left ventricle during the isovolumetric relaxation period has been observed by cineangiography. However, there is little information about blood flow during this period. METHODS: Seventy-nine patients with ischemic heart disease were examined by pulsed Doppler echocardiography and cardiac catheterization. All patients were classified into three groups according to the observed patterns of isovolumetric relaxation flow: group I (n = 41), flow directed toward the apex; group II (n = 21), flow directed toward the base, and group III (n = 17), low velocity flow (< 12 cm/s) without a dominant direction. Patients in group I were further classified into group Ia (n = 19) with normal ventriculograms and group Ib (n = 22) with asynergy. RESULTS: Left ventricular ejection fraction and negative first derivative of left ventricular pressure were significantly lower in group II (49 +/- 9% and 1,274 +/- 212 mm Hg/s, respectively) and group III (38 +/- 8% and 1,147 +/- 280 mm Hg/s, respectively) than in group Ia (68 +/- 7% and 1,727 +/- 358 mm Hg/s), each p < 0.01. Time constant was significantly prolonged in group II (49 +/- 6 ms) and group III (48 +/- 6 ms) compared with that in group Ia (41 +/- 6 ms), p < 0.05. On left ventriculography, patterns of outward wall motion during the isovolumetric relaxation period were associated with the patterns of isovolumetric relaxation flow. CONCLUSIONS: Changes in left ventricular relaxation are accompanied by alterations in isovolumetric relaxation flow. It is therefore useful to evaluate isovolumetric relaxation flow when investigating early diastolic ventricular function. PMID- 8473643 TI - Percutaneous transluminal coronary angioplasty in chronic coronary artery occlusion. AB - OBJECTIVES: This study was conducted to determine the procedural success rate, complication rate and long-term outcome of percutaneous transluminal coronary angioplasty in chronically occluded coronary arteries. BACKGROUND: Coronary angioplasty of chronically occluded vessels has a lower success rate than has angioplasty of nonoccluded vessels, but it is frequently considered safe because the target vessel is already occluded. The purpose of this study was to determine the reliability of these assumptions at our institution, with the objectives stated above. METHODS: We identified from the angioplasty data base at our institution 100 consecutive coronary angioplasty procedures performed between 1987 and 1991 for chronic total occlusion, defined as complete occlusion (Thrombolysis in Myocardial Infarction [TIMI] grades 0 and 1 flow) for > or = 3 months. The records of the 95 patients who underwent these procedures were reviewed to determine procedural outcome and medium-term results. RESULTS: Procedural success was obtained in 47 occluded vessels (47%). Significantly fewer successes were obtained in the right coronary artery (26.8%) than in either the left anterior descending (57.1%) or the left circumflex (45%) coronary artery (p < 0.05). A procedural failure without serious adverse consequences occurred in 45 procedures (45%), but in eight patients (right coronary artery in five, left anterior descending artery in three) attempted recanalization was complicated by extensive coronary dissection with acute myocardial ischemia, and one of these patients died. There were no emergency operations, but elective coronary artery bypass surgery was undertaken in 26 patients (in 3 after extensive dissection, in 7 after an apparently good result and in 16 in whom the procedure failed). At 12 months after the procedure, 64.1% of those with a procedural success were event free compared with 32.6% of those whose procedure was both unsuccessful and uncomplicated (p < 0.025) and 25% of those in whom it was unsuccessful and complicated by coronary dissection (p < 0.025). CONCLUSIONS: In this series of recanalization of chronically occluded coronary arteries, there was a low procedural success rate, particularly for the right coronary artery. However, when procedural success was obtained, the long-term outlook was good. The overall risk of coronary dissection was comparable to the risk in nonoccluded vessels but was particularly high in the right coronary artery (13%). PMID- 8473644 TI - Aspirin, but not heparin, suppresses the transient increase in thromboxane biosynthesis associated with cardiac catheterization or coronary angioplasty. AB - OBJECTIVES: We sought to study the dose dependence of in vivo suppression by aspirin of enhanced thromboxane biosynthesis in the setting of coronary angioplasty and to evaluate the effects of heparin and aspirin during cardiac catheterization. BACKGROUND: Percutaneous transluminal coronary angioplasty induces a controlled injury of the intima of the diseased arterial segment, with rapid deposition of platelets at the site of dilation. Thus, it provides a clinical model of intracoronary platelet activation. METHODS: The urinary excretion of a major enzymatic metabolite of thromboxane A2, 11-dehydro thromboxane B2, was measured in 57 patients with stable coronary artery disease undergoing cardiac catheterization (n = 28) or elective single-vessel percutaneous transluminal coronary angioplasty (n = 29). Three consecutive urine collections were obtained from all patients before during and after either procedure. Patients undergoing catheterization were treated with the following regimens: a) no aspirin for > or = 10 days and no heparin (n = 12); b) no aspirin for > or = 10 days but heparin, 10,000 IU, at the time of catheterization (n = 5); c) aspirin, 300 mg/day, for at least 5 days (n = 11). Patients undergoing coronary angioplasty were randomly assigned to short-term treatment with aspirin given as a) 75 mg/day for > or = 5 days before angioplasty (n = 11); b) 300 mg/day for > or = 3 days before angioplasty (n = 9); or c) 300 mg/day for > or = 3 days before angioplasty followed by 1,000 mg during angioplasty (n = 9). RESULTS: In patients undergoing catheterization, urinary 11-dehydro-thromboxane B2 excretion (pg/mg creatinine) increased from 563 +/- 481 (mean +/- SD) to 1,684 +/- 1,332 in the absence and from 620 +/- 191 to 1,588 +/- 597 in the presence of heparin. No increase was observed in the group receiving aspirin (from 240 +/- 141 to 215 +/- 115). In patients undergoing coronary angioplasty treated with aspirin, 75 mg/day, urinary 11-dehydro-thromboxane B2 averaged 180 +/- 112, 223 +/- 178 and 294 +/- 260, respectively, before, during and after the procedure. At 300 mg/day, the corresponding values were 185 +/- 48, 217 +/- 70 and 197 +/- 93. In patients also receiving aspirin, 1,000 mg, during angioplasty, 11-dehydro thromboxane B2 averaged 151 +/- 66, 138 +/- 43 and 133 +/- 77, respectively. CONCLUSIONS: Enhanced thromboxane biosynthesis associated with cardiac catheterization or coronary angioplasty can be largely suppressed by low dose aspirin. This finding is consistent with the view that this alteration reflects platelet activation. PMID- 8473645 TI - Restenosis after directional coronary atherectomy and balloon angioplasty: comparative analysis based on matched lesions. AB - OBJECTIVES: Late lumen narrowing after directional coronary atherectomy was assessed by quantitative coronary angiography and compared with that after balloon angioplasty. BACKGROUND: Directional coronary atherectomy has been introduced as an alternative technique for balloon angioplasty and may reduce the incidence of restenosis. METHODS: A prospectively collected consecutive series of 87 native coronary artery lesions successfully treated with atherectomy were matched with 87 coronary artery lesions selected from a consecutive series of lesions that had been successfully dilated by balloon angioplasty. Late angiographic analysis was performed in 158 lesions. The net gain index represents the ultimate gain in minimal lumen diameter at follow-up study, normalized for the vessel size. This index is the result of the relative gain attained during the procedure (the ratio of the change in minimal lumen diameter and reference diameter) and the relative loss observed during the follow-up period (the ratio of the change in minimal lumen diameter during the follow-up period and the reference diameter). RESULTS: Matching for clinical and angiographic variables resulted in two comparable groups with similar baseline stenosis characteristics. Atherectomy resulted in a more pronounced increase in minimal lumen diameter than did balloon angioplasty (mean +/- SD 1.17 +/- 0.29 to 2.44 +/- 0.42 mm vs. 1.21 +/- 0.38 to 2.00 +/- 0.36 mm, p < 0.001). However, this favorable immediate result was subsequently lost during late angiographic follow-up, so that the minimal lumen diameter at follow-up and the net gain index did not differ significantly between the two groups (1.76 +/- 0.62 vs. 1.77 +/- 0.59 mm, p = 0.93, and 0.18 +/- 0.19 vs. 0.17 +/- 0.17, p = 0.70). Consequently, the relative gain and relative loss were higher in the atherectomy group. For both techniques, the relative gain was linearly related to the relative loss but the slope of the regression line was steeper for atherectomy, suggesting that the relative loss in the atherectomy group is proportionally even larger for a given relative gain compared with that in the angioplasty group. CONCLUSIONS: In matched groups of patients, atherectomy induces a greater initial gain in minimal lumen diameter than does balloon angioplasty. However, the vascular wall injury induced by the device is of a different nature (debulking vs. dilating) that leads to more relative loss over the follow-up period in the atherectomy group. PMID- 8473646 TI - Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. AB - OBJECTIVE: This study evaluated the impact of early patency of the infarct related vessel on short-term mortality after thrombolysis for acute myocardial infarction. BACKGROUND: Different thrombolytic regimens for acute myocardial infarction proved to be equally effective in large scale mortality trials despite significant differences in their efficacy with respect to early infarct-related vessel patency as shown in smaller angiographic trials. METHODS: Patients from four German multicenter studies of thrombolysis in acute myocardial infarction were retrospectively evaluated. Of 939 patients with acute myocardial infarction (duration of symptoms < 6 h) treated with thrombolysis, 907 (96.6%) had an angiogram of the infarct-related artery 90 min after the initiation of thrombolytic therapy. The perfusion status was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study criteria. RESULTS: Complete reperfusion (TIMI grade 3) was found in 561 of 907 patients and partial reperfusion (TIMI grade 2) in 122 of 907. Overall, the in-hospital mortality rate was 4.6% (43 patients). In patients with complete reperfusion of the infarct related vessel, the mortality rate was only 2.7% versus 7.1% in patients with an occluded vessel at the 90-min angiogram. This difference was highly significant in univariate as well as in multivariate analysis. In patients with partial perfusion of the infarct vessel, the mortality rate was 6.6%. CONCLUSIONS: The early perfusion status of the infarct-related artery is an independent predictor of short-term survival. However, only complete early reperfusion is associated with a reduced in-hospital mortality rate whereas patients with partial perfusion (TIMI grade 2) have a short-term prognosis similar to that of patients with persistently occluded infarct vessels. Therefore, when used as a surrogate end point for mortality, only TIMI grade 3 perfusion of the infarct vessel should be interpreted as a treatment success of thrombolysis in acute myocardial infarction. PMID- 8473647 TI - Trickle down thrombolysis. PMID- 8473648 TI - Genesis of the Austin Flint murmur: relation to mitral inflow and aortic regurgitant flow dynamics. AB - OBJECTIVES: This study was designed to elucidate the genesis of the Austin Flint murmur. BACKGROUND: The Austin Flint murmur is an apical diastolic rumble associated with significant aortic regurgitation. The precise mechanism of the murmur remains unclear. METHODS: The relation between the Austin Flint murmur and mitral inflow and aortic regurgitant flow dynamics was evaluated nonivasively in 13 patients with moderate to severe aortic regurgitation and 15 control subjects using phonocardiographic and pulsed and color-coded Doppler echocardiographic techniques. The severity of aortic regurgitation was determined by color-coded Doppler echocardiography on the basis of the maximal distance of the regurgitant signal. RESULTS: The direction of aortic regurgitant flow was unrelated to the presence of the Austin Flint murmur. The severity of aortic regurgitation was greater in patients with than in those without this murmur. The peak mitral inflow velocity during early diastole (E) was significantly increased, and both peak mitral inflow velocity at atrial contraction (A) and the A/E ratio were significantly decreased in patients with the Austin Flint murmur compared with values in those without this murmur or in control subjects. However, the maximal amplitude of the Austin Flint murmur did not coincide temporally with the peak mitral inflow velocity. The murmur continued both after rapid mitral inflow had ended and during diastolic mitral regurgitation. CONCLUSIONS: The increased velocity of early diastolic mitral inflow in patients with the Austin Flint murmur is due to aortic regurgitation, but rapid mitral inflow is not an essential requirement for production of the murmur. In some cases, the Austin Flint murmur may be generated by aortic regurgitant flow alone. PMID- 8473649 TI - Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter-defibrillator therapy. AB - OBJECTIVES: This study was undertaken to characterize the outcome of survivors of ventricular fibrillation with no or minimal structural heart disease who received an implantable cardioverter-defibrillator. BACKGROUND: The prognosis among survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities remains unclear. Since the advent of implantable cardioverter defibrillators, this question takes on added importance. METHODS: This 10-center retrospective study provided information on 28 survivors of ventricular fibrillation (mean age 42 years) with minimal or no structural abnormalities who were treated with an implantable cardioverter-defibrillator. RESULTS: Ventricular tachyarrhythmias (polymorphic in all but one patient) were induced during baseline programmed stimulation in 39% of patients. During a median 30.6-month follow-up period after implantable cardioverter-defibrillator implantation, there were no cardiac deaths and two noncardiac deaths. Sixteen patients experienced 36 shock episodes (total 88 shocks). The majority of shocks were classified as "indeterminate"; one patient received 47 "spurious" shocks during one shock episode and each of four patients received one "appropriate" shock. Ventricular arrhythmias were not inducible in any of these latter four patients. CONCLUSIONS: Survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities receiving an implantable cardioverter-defibrillator have an excellent 3-year survival rate. The occurrence, albeit infrequent, of appropriate implantable cardioverter-defibrillator shocks in this group suggests that these patients have a potential risk of recurrent cardiac arrest whose fatal outcome may be avoided by implantable cardioverter-defibrillator therapy. PMID- 8473650 TI - Randomized controlled comparison of antitachycardia pacing algorithms for termination of ventricular tachycardia. AB - OBJECTIVES: This study compared the efficacy and safety of two antitachycardia pacing algorithms in the treatment of ventricular tachycardia. BACKGROUND: There is agreement that antitachycardia pacing should be adapted to tachycardia rate and be delivered in a burst, but the ideal pacing pattern is not well understood. Effective antitachycardia pacing burst patterns include those with a between burst decrement (SCAN) with or without an additional within-burst decrement (RAMP). METHODS: Prospective randomized crossover comparison of two antitachycardia pacing algorithms (RAMP vs. SCAN) on identical induced sustained ventricular tachycardias was performed. RESULTS: Sixty-five ventricular tachycardias (mean cycle length 364 +/- 74 ms) from 37 invasive studies performed in 29 patients were studied; 86% of patients had coronary artery disease and 72% were receiving antiarrhythmic therapy at the time of study. Of the 65 tachycardias, 40 were identical pairs and 25 were unpaired (including 8 with a > 30-ms difference in cycle length of induced ventricular tachycardia pairs). In the paired pacing trials, conversion to sinus rhythm occurred, respectively, in 85% of SCAN versus 90% of RAMP protocols (p = 0.63, power = 93%) and within 1.4 +/- 0.7 versus 1.7 +/- 1.1 attempts (p = 0.41). Discordance for pacing success was seen in three pairs. In unpaired trials, conversion to sinus rhythm occurred in 73% and 57%, respectively (p = 0.68, power = 88%). Tachycardia acceleration during pacing occurred in 7 (11%) of 65 attempts (5 SCAN, 2 RAMP). Acceleration in unpaired ventricular tachycardia trials was correlated with tachycardia cycle length. Failure to convert ventricular tachycardia was associated with a shorter tachycardia cycle length (p < 0.05). CONCLUSIONS: In the patients studied, adaptive antitachycardia pacing was safe and effective and, when successful, occurred within three attempts of an 8-beat adaptive burst algorithm. Changes in burst pattern did not affect pacing safety or efficacy. Antitachycardia pacing success was dependent on induced ventricular tachycardia cycle length. PMID- 8473651 TI - Value of signal-averaged electrocardiography, radionuclide ventriculography, Holter monitoring and clinical variables for prediction of arrhythmic events in survivors of acute myocardial infarction in the thrombolytic era. AB - OBJECTIVES: This study assessed the ability of signal-averaged electrocardiography, radionuclide ventriculography and Holter electrocardiographic (ECG) monitoring and clinical variables to identify patients at risk of serious arrhythmic events after myocardial infarction in the thrombolytic era. BACKGROUND: Most studies of signal-averaged electrocardiography, radionuclide ventriculography and Holter ECG monitoring in risk stratification after myocardial infarction preceded the introduction of thrombolytic therapy. METHODS: A consecutive series of 301 survivors of myocardial infarction, 205 (68%) of whom received thrombolytic agents, underwent signal-averaged electrocardiography (1st 48 h, day 6 and discharge), Holter ECG monitoring (days 6 to 7) and radionuclide left ventriculography (days 7 to 14). Median follow-up time was 1.03 years. RESULTS: Thirteen patients (4.3%) had an arrhythmic event (sudden death in 11, sustained ventricular tachyarrhythmia in 2). The 25-Hz high pass filtered signal-averaged ECG at discharge was 64% sensitive (95% confidence intervals [CI] 36% to 92%) and 81% specific (95% CI 76% to 86%). High grade ventricular ectopic activity on the Holter ECG was only 38% sensitive (95% CI 12% to 64%) and 74% specific (95% CI 71% to 77%). Left ventricular ejection fraction < 0.4 was the best test for prediction of arrhythmic events (sensitivity 75% [95% CI 50% to 100%] and specificity 81% [95% CI 76% to 85%]). In multivariate analysis, in rank order, digoxin therapy at discharge, an abnormal 25-Hz signal-averaged ECG before discharge, absence of angina before index infarction and previous infarction were predictive of arrhythmic events. With digoxin therapy excluded, ejection fraction was an independent predictor. Discriminant analysis identified a high risk group (12% of the study patients) with an event rate of 26%. CONCLUSIONS: The signal-averaged ECG and left ventricular ejection fraction are each independently predictive of arrhythmic events after myocardial infarction, but the Holter ECG is not. A combination of clinical and investigative variables, including the signal averaged ECG, best identifies patients at highest risk. PMID- 8473652 TI - Effects of procainamide on the signal-averaged electrocardiogram in relation to the results of programmed ventricular stimulation in patients with sustained monomorphic ventricular tachycardia. AB - OBJECTIVES: The aim of this study was to assess the ability of the signal averaged electrocardiogram (ECG) to predict the efficacy of procainamide. BACKGROUND: The main role of the signal-averaged ECG has been the identification of postinfarction patients at risk of sudden death. Prediction of the efficacy of antiarrhythmic drugs represents another potential clinical application of this technique. METHODS: The study examined the effects of procainamide on the time domain and spectral temporal analysis of the signal-averaged ECG in relation to the results of programmed ventricular stimulation studies in 31 patients with inducible sustained monomorphic ventricular tachycardia. RESULTS: Procainamide significantly prolonged the total and the initial QRS complex and low amplitude signal durations (mean +/- SD 135 +/- 30 vs. 161 +/- 46 ms, p < 0.0001; 87 +/- 16 vs. 98 +/- 20 ms, p < 0.0001, and 48 +/- 23 vs. 63 +/- 36 ms, p < 0.001, respectively) whereas the root-mean-square voltage of the total QRS complex and of the last 40 ms of the QRS complex was significantly reduced (mean +/- SD 112 +/- 36 vs. 87 +/- 36 microV, p < 0.0001; 21 +/- 19 vs. 13 +/- 12 microV, p < 0.002, respectively). The results of spectral temporal mapping of the signal averaged ECG were similar before and after procainamide administration. Procainamide prevented the inducibility of sustained ventricular tachycardia or prolonged the cycle length of ventricular tachycardia by > or = 100 ms in 16 patients (52%) (responders). The fractional prolongation of the total QRS duration was significantly greater in responders (26 +/- 15%) than in nonresponders (10 +/- 10%) (p < 0.002) and, when this prolongation was > or = 15%, identified responders with a sensitivity of 94%, a specificity of 87% and an overall predictive accuracy of 90%. CONCLUSIONS: The effects of procainamide on inducibility of ventricular tachycardia during programmed ventricular stimulation can be predicted by the degree of drug-induced prolongation of the signal averaged QRS complex. PMID- 8473653 TI - Effect on coronary artery anatomy of radiofrequency catheter ablation of atrial insertion sites of accessory pathways. AB - OBJECTIVES: The purpose of this study was to analyze the effects of radiofrequency catheter ablation of the atrial insertion site of accessory pathways on the angiographic appearance of coronary arteries. BACKGROUND: Radiofrequency catheter ablation of accessory pathways requires the application of energy to the endocardial surface of the atrioventricular groove adjacent to the major epicardial coronary arteries. A systematic analysis of the effect of radiofrequency ablation on coronary arteries has not previously been demonstrated. METHODS: Seventy consecutive patients with 76 accessory pathways (7 right free wall, 44 left free wall, 12 posteroseptal, 8 anteroseptal and 5 midseptal) were studied. Quantitative coronary angiography was performed before, immediately after and a mean of 69 +/- 42 days after radiofrequency catheter ablation. RESULTS: Coronary artery diameter adjacent to the ablating electrode was 2.6 +/- 0.9 mm before ablation, 2.7 +/- 0.9 mm immediately after ablation and 2.7 +/- 1.0 mm at the time of follow-up study. Angiographic findings were unchanged from baseline in 69 of 70 patients immediately after ablation and in all 70 patients at the time of follow-up study. CONCLUSIONS: Radiofrequency catheter ablation of the atrial insertion site of accessory pathways does not result in short-term angiographic changes in coronary artery anatomy. PMID- 8473654 TI - Effect of therapy with an angiotensin-converting enzyme inhibitor on hemodynamic and counterregulatory responses during continuous therapy with nitroglycerin. AB - OBJECTIVES: We sought to characterize the reflex counterregulatory responses throughout a 6-day period of continuous nitroglycerin therapy and to examine the effect of concurrent administration of a non-thiol angiotensin-converting enzyme inhibitor (benazepril) on the nature of those responses. BACKGROUND: Therapy with nitroglycerin has been shown to be associated with reflex counterregulatory responses. METHODS: Standing systolic blood pressure, hormonal responses, urinary sodium and hematocrit levels were monitored during 6 days of continuous transdermal nitroglycerin therapy in normal volunteers. Using a double-blind randomized parallel design, 11 subjects received placebo and 9 received benazepril. Hemodynamic responses to sublingual nitroglycerin administration were evaluated before and after sustained therapy with transdermal nitroglycerin. RESULTS: Attenuation of the hypotensive response to transdermal nitroglycerin was rapid in the group receiving placebo and the group receiving benazepril. There were no significant hormonal responses to transdermal nitroglycerin in either group, and sodium retention was modest and transient. Hematocrit levels decreased after transdermal nitroglycerin therapy and remained depressed for the duration of nitroglycerin therapy, a finding that suggests plasma volume expansion. Blood pressure responses to sublingual nitroglycerin in both groups were similar before and after continuous transdermal nitroglycerin therapy. CONCLUSIONS: These data suggest that plasma volume expansion plays a more important role than neurohormonal responses in the loss of nitrate effects during sustained therapy. That therapy with an angiotensin-converting enzyme inhibitor did not modify the hemodynamic responses to continuous nitroglycerin therapy supports this conclusion. Further investigation will be necessary to confirm whether therapy with an angiotensin-converting enzyme inhibitor has any role in the prevention of nitrate tolerance. PMID- 8473655 TI - Left ventricular diastolic dysfunction late after coarctation repair in childhood: influence of left ventricular hypertrophy. AB - OBJECTIVES: Left ventricular systolic and diastolic function were evaluated late after successful operation for aortic coarctation in childhood. BACKGROUND: Persistent arterial hypertension and left ventricular hypertrophy after coarctation repair might impair left ventricular function. METHODS: Biplane angiography and simultaneous high fidelity pressure measurements were performed in 12 patients 3 to 12 years postoperatively (residual pressure gradient 4 mm Hg). Eight patients were normotensive and four had borderline hypertension. Data at rest and after nitroprusside infusion (1.7 micrograms/kg per min) were evaluated and compared with data from 12 control subjects. RESULTS: Systolic left ventricular function (ejection fraction-end-systolic wall stress relation) was normal in all patients. However, left ventricular muscle mass (113 vs. 86 g/m2), right atrial pressure (5.2 vs. 1.9 mm Hg) and left ventricular end-diastolic pressure (16 vs. 11 mm Hg) were significantly higher in patients than in control subjects. There was a linear relation between muscle mass and left ventricular end-diastolic (r = 0.66, p < 0.001) or right atrial (r = 0.60, p < 0.01) pressure. Left ventricular relaxation and myocardial stiffness were normal. However, there was an upward shift of the diastolic pressure-volume curve when compared with control values, but this shift was reversed by the administration of nitroprusside. CONCLUSIONS: Systolic function is normal late after coarctation repair. However, diastolic function can be abnormal with an upward shift of the diastolic pressure-volume curve that is reversed by nitroprusside administration and is probably due to residual left ventricular hypertrophy. PMID- 8473656 TI - Selective pulmonary and systemic vasodilator effects of amrinone in children: new therapeutic implications. AB - OBJECTIVES: The present study was performed to determine the systemic and pulmonary hemodynamic effects of amrinone in infants and children with a cardiac left to right shunt to determine if there is a beneficial effect on the pathophysiology of this condition. BACKGROUND: Amrinone is a bipyridine derivative with inotropic and vasodilator effects that have not been systematically evaluated in the pediatric patient with increased pulmonary blood flow. METHODS: Nineteen patients (aged 2 months to 8.3 years) with one or more left to right shunts were evaluated during cardiac catheterization with direct hemodynamic measurements made before and 10 min (peak effect) after administration of a bolus injection of amrinone, 3 mg/kg body weight. The Fick method was used to calculate pulmonary and systemic blood flow, and resistances were then calculated. RESULTS: In group A, five patients with normal pulmonary artery pressure and resistance, amrinone significantly reduced mean pulmonary artery pressure by 19%, mean left atrial pressure by 39% and systemic vascular resistance by 17%. In group B, seven patients with pulmonary artery hypertension (mean pulmonary artery pressure > 20 mm Hg) and normal pulmonary vascular resistance (total pulmonary resistance < or = 3 Wood U.m2), amrinone significantly reduced the pulmonary artery pressure by 27%, systolic aortic pressure by 5%, mean aortic pressure by 12%, pulmonary arteriolar resistance by 36% and total pulmonary vascular resistance by 26%. In group C, seven patients with pulmonary artery hypertension (mean pulmonary artery pressure > 20 mm Hg) and elevated pulmonary vascular resistance (total pulmonary resistance > 3 Wood U.m2), amrinone significantly reduced the pulmonary arteriolar resistance by 49%, total pulmonary resistance by 47% and pulmonary arteriolar/systemic vascular resistance ratio by 45% and increased the heart rate by 15%. CONCLUSIONS: In children with a cardiac left to right shunt, amrinone 1) appears to have selective vasodilator effects depending on the pulmonary artery pressure and resistance, 2) has a beneficial hemodynamic effect in children with normal pulmonary artery pressure and resistance, and 3) may have a role in the treatment of patients with pulmonary artery hypertension without causing systemic hypotension. PMID- 8473657 TI - Cardiac teratogenesis of halogenated hydrocarbon-contaminated drinking water. AB - OBJECTIVES: The purpose of this study was to test the hypothesis that administration of trichloroethylene and dichloroethylene to pregnant rats during organogenesis would produce a significant fetal cardiac teratogenic effect. It was also hypothesized that administration of these compounds only before pregnancy would not be associated with fetal cardiac teratogenesis. BACKGROUND: Epidemiologic observations demonstrated an increased number of congenital cardiac defects in children whose mother resided in an area with drinking water contaminated by trichloroethylene and dichloroethylene. A prior provocative intrauterine exposure study in rats established a positive link between these contaminants and an increased number of fetal hearts with congenital cardiac defects. METHODS: Sprague-Dawley rats were given pure tap drinking water (control subjects) or water contaminated with high or low dose of trichloroethylene or dichloroethylene (experimental groups) during prepregnancy only, prepregnancy and pregnancy or during pregnancy alone. RESULTS: A total of 2,045 fetuses were examined. Trichloroethylene or dichloroethylene delivered exclusively in the period before pregnancy caused no increase in congenital cardiac malformations over the control level. Compared with the control group, rats exposed to these agents both before and during pregnancy, had a significantly greater number of fetuses with cogenital cardiac malformations. Trichloroethylene (high dose only) administered only during pregnancy produced a significant increase in cardiac defects. Other fetal variables, including noncardiac congenital abnormalities, showed no significant difference between control and treated groups. CONCLUSIONS: Trichloroethylene and dichloroethylene administered during organogenesis are cardiac, but not general, teratogens. The data indicate that these agents administered in drinking water to pregnant rats caused an increased number of congenital cardiac defects in rat fetuses. PMID- 8473658 TI - Heart disease and the environment. PMID- 8473659 TI - Estimation of right ventricular mass in normal subjects and in patients with primary pulmonary hypertension by nuclear magnetic resonance imaging. AB - OBJECTIVES: This study was designed to test the accuracy of nuclear magnetic resonance (NMR) imaging as a noninvasive technique for estimating right ventricular mass in normal subjects and in patients with primary pulmonary hypertension. BACKGROUND: An accurate means of noninvasively estimating right ventricular mass may allow better characterization of the degree of right-sided pressure or volume overload caused by underlying cardiac or pulmonary diseases. METHODS: End-diastolic short-axis electrocardiogram (ECG)-gated spin echo NMR images of the heart were obtained in vivo in 13 patients with primary pulmonary hypertension and 10 normal adult volunteers. Both right and left ventricular mass were computed by summing the myocardial slice volumes over all slices spanning the myocardium and multiplying by myocardial density. This technique of myocardial mass determination was verified by imaging 10 calf hearts and comparing the NMR-determined right and left myocardial mass with the actual mass determined by weighing the right and left ventricles. RESULTS: In the calf heart study, an excellent correlation was obtained between the directly measured ventricular mass and the NMR-calculated mass, for both the right and the left ventricle. Patients with primary pulmonary hypertension had an elevated right ventricular mass index compared with that of normal subjects (62.69 +/- 8.72 g/m2 vs. 23.32 +/- 1.36 g/m2, p < 0.0005). There was no significant difference in left ventricular mass index between the two groups. Both mean intraobserver and inter observer variability in myocardial mass determination were low. Linear regression analysis between right ventricular mass index and mean pulmonary artery pressure was significant (r = 0.75, p < 0.003). CONCLUSIONS: Electrocardiogram-gated spin echo NMR imaging of the heart may be used for quantitating right ventricular mass in normal subjects and in patients with primary pulmonary hypertension, in whom it may also provide an alternative noninvasive technique for estimating mean pulmonary artery pressure. PMID- 8473660 TI - Measurement accuracy of cardiac output in humans: indicator-dilution technique versus geometric analysis by ultrafast computed tomography. AB - OBJECTIVES: The aim of this study was to evaluate measurement accuracy of cardiac output in humans by comparing the indicator-dilution technique with geometric analysis by ultrafast computed tomography. BACKGROUND: Ultrafast computed tomography can be used to measure cardiac output by two methods. First, by scanning to obtain end-systolic and end-diastolic short-axis images of the ventricular cavities at sequential tomographic levels, the stroke volume and therefore the cardiac output can be calculated. Second, indicator-dilution theory (the Stewart-Hamilton equation) can be applied to measurements of the concentration of radiographic contrast in the blood pool after a bolus injection. The latter method has not been validated in humans. METHODS: The accuracy of the geometric method itself was first established by comparing left and right ventricular stroke volumes in 29 patients without valvular regurgitation or an intracardiac shunt, whose left and right ventricular stroke volumes should have been identical (group A). In a subset of 17 patients, the geometric method was compared with the indicator-dilution method (group B). RESULTS: Geometric analysis showed that the mean difference between left and right ventricular stroke volume was 1.8 +/- 7.3 ml, with a percentage SD of the differences of 9.3% (r = 0.9). Comparison wih indicator dilution-calculated cardiac output showed a mean difference of 0.079 +/- 1.22 liters/min, with a percent SD of the differences of 23.7% (r = 0.6). There was no improvement in this comparison with individual calibration of the scanner for each patient. CONCLUSIONS: The disparity found between data obtained with the geometric and indicator-dilution methods may be a result of the hemodynamic effects of contrast medium or it may suggest the possibility that some assumptions of indicator-dilution theory are not valid. PMID- 8473661 TI - Is the Watanabe heritable hyperlipidemic rabbit a suitable experimental model for percutaneous transluminal coronary angioplasty in humans? A light microscopic, immunohistochemical and ultrastructural study. AB - OBJECTIVES: This study was designed to assess an experimental model for the study of mechanisms that underlie restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND: The Watanabe heritable hyperlipidemic (WHHL) rabbit lacks the receptor for low density lipoproteins, produces atherosclerotic lesions very similar to those in humans and, therefore, could serve as a suitable model. METHODS: Percutaneous transluminal angioplasty was performed on the left subclavian artery of 10 homozygous rabbits. The animals were killed at a few hours or 3, 7, 14 or 28 days after the procedure. The artery was fixed by perfusion, and the site of angioplasty was examined by both light and electron microscopy with the use of conventional and immunohistochemical staining techniques. RESULTS: Angioplasty had caused a flap-like or dissecting tear into the media. At day 3, cells within the preexisting media adjacent to the injury had the ultrastructural characteristics of synthetic smooth muscle cells. At day 7, spindle cells at the site of injury stained either negative or very weakly positive with a marker for actin; ultrastructurally, these cells had the synthetic phenotype. At day 14, the spindle cells showed a mix of contractile and synthetic phenotypes. The surface was partially covered by endothelial cells. At day 28, the dominant cell type was the contractile smooth muscle cell and the surface was completely covered by endothelial cells. CONCLUSIONS: Both the injury and the response to injury after percutaneous transluminal angioplasty were almost identical to that seen in humans after coronary angioplasty. Thus, the WHHL rabbit appears to be an appropriate experimental model for use in further studies. PMID- 8473662 TI - Coronary circulation in dogs with an experimental decrease in aortic compliance. AB - OBJECTIVES: This study was designed to investigate the effects of decreased aortic compliance on the coronary circulation. BACKGROUND: A decrease in aortic compliance due to arteriosclerosis is observed in patients with coronary artery disease. However, the effects of decreased aortic compliance on the coronary circulation have not yet been investigated sufficiently. METHODS: Hemodynamics, subendocardial electrocardiogram (ECG), myocardial segmental length and myocardial blood flow were investigated in six dogs with aortic bandaging (bandaged group) and five dogs with a sham operation (control group) at rest and during pacing 4 weeks after surgery. RESULTS: Aortic compliance in the bandaged group was less than that in the control group (0.24 +/- 0.20 vs. 0.50 +/- 0.22 ml/mm Hg, p < 0.05). Pulse pressure and the tension-time index were significantly greater in the bandaged group than in the control group, but systemic vascular resistance was not altered significantly. The subendocardial/subepicardial flow ratio was lower in the bandaged group than in the control group (0.95 +/- 0.31 vs. 1.57 +/- 0.26, p < 0.05). In the region supplied by the left circumflex artery with a stenosis that was adjusted to eliminate reactive hyperemia, rapid atrial pacing (heart rate 200 beats/min) further decreased endocardial flow and the endocardial/epicardial flow ratio in the bandaged group. Moreover, both the reduction of segmental shortening and the ST elevation on the subendocardial ECG in the left circumflex-supplied region during pacing were greater in the bandaged group. CONCLUSIONS: These results indicate that decreased aortic compliance greatly increases the risk of subendocardial ischemia in the presence of coronary stenosis. PMID- 8473663 TI - Ultrasound enhancement of thrombolysis and reperfusion in vitro. AB - OBJECTIVES: The aims of this study were 1) to develop an in vitro flow system in which reperfusion mediated by ultrasound-accelerated thrombolysis could be studied, and 2) to test whether ultrasound-accelerated thrombolysis could hasten reperfusion in this system. BACKGROUND: Ultrasound has been shown to increase tissue plasminogen activator (t-PA)-induced thrombolysis in vitro as assessed by radioactive fibrinogen release from labeled clots and in an animal in vivo model. METHODS: To test whether reperfusion is accelerated, we created obstructive whole blood clots in an in vitro flow system. Four control clots were exposed to ultrasound only without any thrombolytic agent (group 1). Sixteen clots were exposed to continuous infusion of recombinant tissue-type plasminogen activator rt-PA and randomized to either continuous wave ultrasound exposure at a frequency of 0.5 MHz and an intensity of 8 W/cm2 (group 2) or to no ultrasound (group 3). Flow distal to the clot and the rate of release of radiolabeled fibrin products were used as an index of reperfusion and thrombolysis, respectively. Samples were obtained for measurements of lytic variables such as plasminogen, fibrinogen and rt-PA concentrations. RESULTS: Flow was significantly higher in the rt-PA-treated clots within 10 min of exposure to ultrasound than in those without such exposure (9.4 +/- 9.9% of maximal flow in group 2 vs. 0.5 +/- 1.5% in group 3, p < 0.05). The maximal difference in flow between groups 2 and 3 was achieved at 25 min (61.0 +/- 30.4% vs. 14.2 +/- 14.7%, p = 0.03). Thrombolysis was significantly higher after 15 min of ultrasound exposure (12.8 +/- 9.1% in the ultrasound treated group 2 vs. 4.0 +/- 3.9% in group 3, p < 0.05). The maximal difference between groups 2 and 3 occurred at 25 min (26.7 +/- 13.1% vs. 7.24 +/- 5.7%, p < 0.004). Neither flow nor clot lysis occurred in group 1. Plasminogen and fibrinogen concentrations and rt-PA antigen concentrations were consistent with those observed during fibrinolytic therapy in vivo. CONCLUSIONS: Continuous wave ultrasound at 0.5 MHz and an intensity of 8 W/cm2 accelerates rt-PA-induced thrombolysis and reperfusion in vitro. PMID- 8473664 TI - Low pressure radiofrequency balloon angioplasty: evaluation in porcine peripheral arteries. AB - OBJECTIVES: The purpose of this study was to evaluate the efficacy of radiofrequency-powered thermal balloon angioplasty in an in vivo porcine model. BACKGROUND: Various modes of thermal energy used adjunctively during balloon angioplasty have demonstrated the potential to enhance the results of acute lumen dilation. METHODS: In normal pigs, 75 peripheral arteries were dilated with a newly designed, radiofrequency-powered, thermal angioplasty balloon. All inflations were performed at 2-atm pressure for 85 s. Dilations were performed either with (hot) or without (cold) the application of heat. Lumen dimensions and vessel morphology were assessed with intravascular ultrasonography. At the end of each study, dilated arterial segments were harvested for histologic examination. RESULTS: Single cold balloon inflations resulted in a 12.7% increase in arterial cross-sectional area whereas single hot inflations resulted in a 22.9% increase (p < 0.03). Similarly, when multiple cold inflations were compared with multiple hot inflations, two, three and four sequential hot inflations resulted in a significantly greater increase in cross-sectional area than an equivalent number of cold inflations (p < 0.03). Histologic examination demonstrated a temperature dependent effect on the depth of medial necrosis and extent of arterial wall thinning (p < 0.001) as well as evidence for uniform alteration of elastic tissue fibers at temperatures of > or = 60 degrees C (p < 0.03). CONCLUSIONS: Low pressure radiofrequency thermal balloon angioplasty results in a greater increase in cross-sectional area in porcine peripheral arteries than does nonheated conventional balloon angioplasty. The pathologic basis for this enhanced dilation may be a temperature-dependent effect on medial necrosis, thinning of the arterial wall or alteration of vascular elastic fibers, alone or in combination. PMID- 8473665 TI - Coupling between regional myocardial oxygen consumption and contraction under altered preload and afterload. AB - OBJECTIVES: This study was designed to assess the relation between left ventricular regional myocardial oxygen consumption (VO2) and variables of regional myocardial contractile function under various loading conditions. BACKGROUND: Although the relation between global VO2 and global ventricular function has been extensively studied, the relation between regional VO2 and regional myocardial contraction is not fully understood. METHODS: Myocardial shortening (regional area shrinkage), regional work, regional total mechanical energy index and regional VO2 were measured under variously altered loading conditions in the isolated, blood-perfused dog left ventricle. Regional total mechanical energy per beat was quantified by wall tension-regional area area (TAA) by the analogy of left ventricular pressure-volume area. Left ventricular loading conditions were altered by changing end-diastolic volume and stroke volume with a servo pump as follows: 1) increased preload (increased end diastolic volume and stroke volume at a constant ejection fraction), 2) decreased afterload (increased stroke volume at a constant end-diastolic volume), 3) increased preload and afterload (increased end-diastolic volume at a constant stroke volume), and 4) altered mode of contraction (ejecting vs. isovolumetric contractions). RESULTS: During increased preload, all three variables correlated positively with regional VO2 (r = 0.78 to 1.00). During decreased afterload, the correlation was negative for area shrinkage (r = -0.65 to -0.91) and variable for regional work (r = -0.55 to 0.98) but positive and highly linear for TAA (r = 0.80 to 0.99). During increased preload and afterload, the correlation was again negative for area shrinkage (r = -0.77 to -0.97) but positive for regional work (r = 0.83 to 0.93) and TAA (r = 0.95 to 0.99). During altered mode of contraction, the correlation was insignificant for area shrinkage (r = 0.24 to 0.57) and moderate for regional work (r = 0.50 to 0.79), whereas again highly linear for TAA (r = 0.95 to 0.98). Thus, only TAA correlated closely with regional VO2 under any loading conditions. Furthermore, the slope and regional VO2 intercept of the regional VO2-TAA relation was remarkably consistent among the different hearts and loading conditions. CONCLUSIONS: We conclude that there is a tight coupling between regional VO2 and regional total mechanical energy represented by TAA regardless of left ventricular afterload and preload conditions. PMID- 8473666 TI - What does FACC mean to you? PMID- 8473667 TI - President's page: the prevention paradox. PMID- 8473668 TI - PR interval and heart size in the humpback whale. PMID- 8473669 TI - A major antigen of Alternaria alternata with potential for safe and effective immunotherapy. PMID- 8473670 TI - The effect of vacuum cleaners on the concentration and particle size distribution of airborne cat allergen. AB - BACKGROUND: Vacuum cleaners are essential for the removal of dust from the surface of carpets; however, they may also contribute to airborne dust both by leakage through the cleaner and disturbance of floor dust. METHODS: The present studies used established techniques for measuring airborne Fel d I to study the effects of vacuum cleaners on airborne cat allergen under laboratory conditions and in houses with cats. Nine different models were loaded with dust containing 50 mg Fel d I and run for 15 minutes in a laboratory room (volume approximately 18 m3). Leakage was expressed as the airborne concentration of allergen in nanograms per cubic meter. RESULTS: Cleaners incorporating a double-thickness dust bag either did not leak, that is, less than 0.4 ng Fel d I/m3 or had minor leakage approximately 5 ng/m3. Vacuum cleaners with single-thickness paper bags leaked more, that is, 15 to > 90 ng/m3 with the exception of the cleaner with an efficient outer bag. Detailed studies on a vacuum cleaner that leaked showed that placing dust in the bag, replacing the dust bag with a double-thickness bag, and placing an electrostatic filter over the exhaust reduced levels from greater than 90 ng/m3 to less than 2 ng/m3. Two water-filter vacuum cleaners each emitted cat allergen (up to > 100 ng/m3) with a mean of approximately 90% on particles less than 2.5 microns diameter. This emission could be almost completely controlled by taping electrostatic filter paper over the air outlet. CONCLUSIONS: In houses with cats, different models of vacuum cleaners could either reduce or increase total airborne allergen, and could also selectively increase certain particle sizes. These results suggest that cat allergen is a good model for studying the effectiveness of vacuum cleaners recommended to allergic patients. PMID- 8473671 TI - Trends in the prevalence of asthma hospitalization in the 5- to 14-year-old Michigan Medicaid population, 1980 to 1986. AB - BACKGROUND: Despite advances in therapy, morbidity and mortality rates as a result of pediatric asthma appear to have increased during the past decade. Epidemiologic evidence suggests that these increases disproportionately affected black children and the urban poor. METHODS: With use of data from the Medicaid Management Information System, we estimated the prevalence of asthma hospitalization in the 5- to 14-year-old Michigan Medicaid population for the period 1980 to 1986. RESULTS: Large increases were seen between 1980 and 1984, with leveling off or a slight decline thereafter. In 5- to 9-year-old children, the prevalence of asthma hospitalization increased from 2.3 per 1000 persons in 1980 to 4.5 per 1000 in 1984. Ten- to 14-year-old children demonstrated an increase of 2.2 per 1000 in 1980 to 3.2 per 1000 in 1984. Comparable trends occurred in all strata defined by age, race, residency, and gender. However, the largest increases were noted in urban black children, in which the rate more than doubled from 3.2 per 1000 in 1980 to 7.1 per 1000 in 1984. The adjusted relative risk for asthma hospitalization associated with being male was 1.6 (95% CI: 1.5, 1.7), with being black was 2.2 (95% CI: 2.1, 2.4), and with living in an urban county was 1.1 (95% CI: 1.04, 1.4). CONCLUSIONS: Within this relatively homogeneous low socioeconomic population, black race remained a strong predictor for asthma hospitalization, whereas urban residence was only minimally associated with this outcome. PMID- 8473672 TI - Mite asthma in childhood: a study of the relationship between exposure to house dust mites and disease activity. AB - BACKGROUND: Children with asthma are commonly sensitized to the house dust mite. METHODS: We took monthly measurements from July to December of the amount of mites in the mattresses of asthmatic children and correlated them with symptom score, pulmonary function, and airway hyperreactivity to methacholine. RESULTS: In spite of the high number of Dermatophagoides pteronyssinus throughout this period, symptom and treatment scores, as well as PC20 to methacholine, worsened during the months of September and October. CONCLUSIONS: It is concluded that when asthmatic children allergic to mites are exposed to high levels of mite allergen, the number of mites in the mattress dust no longer correlate with increased symptoms, and that other factors are more likely to be associated with exacerbation. PMID- 8473673 TI - Prepolymers of hexamethylene diisocyanate as a cause of occupational asthma. AB - BACKGROUND: Occupational asthma (OA) caused by products that contain hexamethylene diisocyanate (HDI) has been ascribed to the highly volatile monomer of HDI. Most two-component paints are now made up primarily of nonvolatile prepolymers of HDI (30% to 60%) with only trace amounts (< 0.1%) of the monomer. The respective role of the two chemical forms of HDI in causing OA has never been investigated. METHODS: Twenty workers who were consecutively referred for possible OA that resulted from exposure to spray paints underwent inhalation challenges on separate days with pure HDI monomer and the commercial formulation of HDI prepolymers to which they had been exposed at work. RESULTS: Specific inhalation challenges elicited a positive asthmatic reaction in 10 of the 20 subjects. Among these subjects, four had positive bronchial reactions (two early, one late, and one dual) to both the monomer and the prepolymers. Four other subjects had asthmatic reactions (two early, one late, and one dual) after exposure to the prepolymers but not after exposure to the monomer. The discordance in bronchial response elicited by the monomer and the prepolymers could not be due to differences in the level of baseline nonspecific bronchial reactivity or in HDI concentrations during the tests. One subject showed an atypical progressive reaction after exposure to the monomer but not after exposure to the prepolymer. In this case, the discordant response could be explained by differences in HDI concentration. CONCLUSION: These observations show that, although they are nonvolatile, the prepolymers of HDI can induce OA and that asthmatic reactions as a result of exposure to prepolymers but not the monomer is not a rare occurrence. PMID- 8473674 TI - The effects of season, climate, and air-conditioning on the prevalence of Dermatophagoides mite allergens in household dust. AB - BACKGROUND: Clinical evidence reveals a strong relationship between dust mite allergen levels and asthma. This study suggests the relative importance and interactions among factors that influence mite allergen levels in human dwellings. METHODS: Dermatophagoides pteronyssinus allergen (Der p I) and D. farinae allergen (Der f I) were measured in 536 dust samples collected from 424 homes across the United States. RESULTS: There were distinct seasonal fluctuations of Der p I and Der f I. Der p I rapidly increased to peak in July then gradually decreased through October. Der f I slowly rose to peak later, around September, before declining. Different climates in regions of the United States had no significant affect on the quantity of Der p I or Der f I. However, regional climate differences seemed to influence the prevalence of either D. pteronyssinus or D. farinae. Air-conditioning significantly reduced (p < 0.001) Der I mite allergens detected in the dust samples, and a tendency existed for Der f I to be higher than Der p I in air-conditioned homes. There was a significant (p < 0.01) interaction between air-conditioning and seasons. The most dramatic affect was observed during the summer months, the cooling season, from approximately May to September. CONCLUSIONS: These findings show that distinct seasonal fluctuations exist of D. pteronyssinus and D. farinae mite populations, and suggest that differences in the microclimate within homes may have a dramatic affect on Dermatophagoides mite populations. PMID- 8473675 TI - Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. AB - BACKGROUND: Allergic reactions to measles, mumps, and rubella (MMR) vaccine are rare; some have been attributed to allergy to trace quantities of egg proteins. We report a 17-year-old female who had an anaphylactic reaction to MMR vaccine. A primary vaccination with MMR at age 15 months had been uneventful. She is not allergic to eggs; however, ear and throat pruritus and tongue swelling develop after she eats gelatin. MMR vaccine contains gelatin as a stabilizer. METHODS AND RESULTS: Prick skin tests were positive to 1:10 wt/vol dilutions of MMR vaccine and gelatin but negative to egg. By immunoassay, her serum IgE antibodies were elevated to both MMR vaccine and gelatin, but not to isolated MMR antigens. IgE binding to the gelatin carrier could be inhibited in a dose-dependent fashion by addition of not only MMR vaccine but also gelatin from a variety of animal sources. Immunoblotting confirmed the presence of IgE antibodies to multiple gelatin components as well as to MMR vaccine components. CONCLUSIONS: We conclude that the patient has an anaphylactic sensitivity to gelatin, and that her anaphylaxis to MMR vaccine was caused by the gelatin component. This sensitivity may explain other cases of MMR anaphylaxis. PMID- 8473676 TI - Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma. AB - BACKGROUND: Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma. METHODS: In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone. RESULTS: All groups tolerated a considerable reduction in glucocorticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55% +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone. These reductions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups. The concentration of methacholine required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment group. Safety parameters including blood chemistry and hematology, adrenal function assessment; bone densitometry, and muscle strength testing, were not altered significantly. Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention. Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper. CONCLUSIONS: TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage. Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects. PMID- 8473677 TI - Influence of natural antigenic exposure on expiratory flows, methacholine responsiveness, and airway inflammation in mild allergic asthma. AB - BACKGROUND: This study looked at respiratory symptoms, peak expiratory flow rates (PEFRs), airway responsiveness to methacholine and inflammatory changes on bronchial biopsies, bronchial lavage (BL), and bronchoalveolar lavage (BAL) during natural antigenic exposure in nine subjects with pollen-sensitized seasonal asthma. METHODS: The subjects recorded daily symptoms of asthma, cough and rhinitis, and morning and evening PEFRs between January and September, during and out of the pollen exposure. Baseline forced expiratory volume in 1 second, forced vital capacity, and methacholine responsiveness were measured every 3 to 4 weeks. BAL, BL, and bronchial biopsies were performed in the pollen season at the initial increase of asthma symptoms and out of pollen exposure. RESULTS: At the time of bronchoscopy during the pollen season compared with out of season, asthmatic subjects had an increase in asthma symptom score (1.18 +/- 0.24/0.44 +/ 0.18, p < 0.05), a reduction of PEFR (407 +/- 23/442 +/- 20 L/min, p = 0.02), and a decrease in PC20 (1.15/1.48 mg/ml, p = 0.05). In asthmatic subjects, median BAL and BL cell counts and cell differentials during or out of antigenic exposure were similar, but BAL and BL eosinophils and metachromatic cells counts were always higher than in healthy subjects. In comparison with controls, biopsies obtained in asthmatic subjects showed airway lesions such as epithelial desquamation, squamous cell metaplasia, thickening of basal membrane, inflammatory cells (p < 0.05 for neutrophils), edema, and ciliary abnormalities. During pollen exposure, inflammatory signs increased, but this change was only significant for the extent of epithelial desquamation and neutrophil counts. No significant correlation was found between the intensity of airway inflammation and changes in airway responsiveness. CONCLUSIONS: In subjects with mild allergic asthma and pollen-induced asthma, seasonal antigenic exposure was associated with an increase in epithelial shedding and in the number of neutrophils on bronchial biopsies, suggesting a mild increase in baseline airway inflammation. However, these changes were not correlated with increases in airway responsiveness. PMID- 8473678 TI - Altered platelet function associated with the bronchial hyperresponsiveness accompanying nocturnal asthma. AB - BACKGROUND: Nocturnal awakening is a common feature of bronchial asthma, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether nocturnal awakening is associated with changes in platelet function with the use of a variety of markers of platelet activation. METHODS: Ten patients with a history of nocturnal asthma and 10 age- and sex-matched healthy control subjects were studied at 10:00 PM, 4:00 AM, and 10:00 AM on 2 consecutive days. The following parameters were tested: forced expiratory volume in 1 second (FEV1), log dose of methacholine inducing a 20% fall in FEV1, platelet count and volume, platelet aggregation induced by collagen or activating factor, and plasma and intraplatelet levels of beta-thromboglobulin and platelet factor 4. RESULTS: We have demonstrated that altered platelet function and platelet activation occurs at 4:00 AM in patients with nocturnal asthma and is associated with the maximum increases in bronchial reactivity. Such changes were not observed in 10 control subjects. Platelet dysfunction has been detected as a reduced aggregatory response of platelets to collagen and platelet activating factor such that up to 5 times more platelet activating factor and 1.5 times more collagen were required to elicit a threshold aggregatory response in asthmatic subjects when compared with control subjects; this difference was evident at all time points tested. Furthermore, at 4:00 AM there were significantly lower levels of intraplatelet beta-thromboglobulin corresponding to the maximum reduction in peak expiratory flow and to the maximal increase in bronchial responses to inhaled methacholine. CONCLUSIONS: These results suggest that platelet activation accompanies nocturnal asthma and further suggest that platelets may play a role in this common clinical condition. PMID- 8473679 TI - The effect of BAY u 3405, a thromboxane receptor antagonist, on prostaglandin D2 induced nasal blockage. AB - BACKGROUND: Nasal lavage and challenge studies in allergic rhinitis implicate prostaglandin (PG) D2 in the genesis of nasal blockage. PG D2 is known to act via at least two receptors, the thromboxane prostanoid receptor and the PG D2 prostanoid (DP) receptor; the lower airway effects are mediated chiefly by the TP receptor. The receptor involved in the genesis of PG D2-induced nasal blockage is unknown. BAY u 3405 is a potent selective competitive TP receptor antagonist, which inhibits the lower airway response to PG D2, and shifts the dose-response curve to the right by up to 16-fold. METHODS: The efficacy of a single oral dose of 20 mg of BAY u 3405 was examined in comparison with PG D2 nasal insufflation in a randomized, double-blind, placebo-controlled crossover study, with objective measurement of nasal resistance by active posterior rhinomanometry. RESULTS: BAY u 3405 afforded no protection against PG D2-induced nasal blockage. CONCLUSIONS: This suggests that PG D2-induced nasal blockage may be mediated by the DP receptor rather than the TP receptor and that TP receptor antagonists are unlikely to be of benefit in the treatment of allergic rhinitis. In vivo investigation with specific potent DP receptor antagonists is awaited. PMID- 8473680 TI - Ketotifen inhibits exacerbation of allergic airway hyperreactivity by racemic salbutamol in the guinea pig. AB - In passively sensitized anesthetized guinea pigs, intravenous infusion of low doses of antigen ovalbumin induced a marked increased responsivity of the airways to intravenous injection of leukotriene C4. Sustained infusion of racemic salbutamol intensified responses to leukotriene C4 both before and after infusion of ovalbumin. Hyperreactivity as a result of infusion of ovalbumin was inhibited by intraduodenal injection of either hydrocortisone or ketotifen at doses that did not diminish responses to leukotriene C4 in animals not exposed to antigen. Ketotifen, but not hydrocortisone, inhibited the enhanced hyperreactivity associated with infusion of racemic salbutamol. PMID- 8473681 TI - The role of 5-lipoxygenase products in preclinical models of asthma. AB - BACKGROUND: The action of 5-lipoxygenase on arachidonic acid generates potent inflammatory mediators that may contribute to the pathophysiology of asthma. METHODS: Using the potent and selective 5-lipoxygenase inhibitor BI-L-239, we have examined the role of 5-lipoxygenase products in three animal models of asthma. RESULTS: In vitro BI-L-239 inhibited 5-lipoxygenase product generation from human lung mast cells, alveolar macrophages, and peripheral blood leukocytes with a concentration that would provide 50% inhibition values of 28 to 340 nmol/L. A 36-fold selectivity for immunoreactive leukotriene C4 versus immunoreactive prostaglandin D2 inhibition was demonstrated in mast cells. In anesthetized cynomolgus monkeys, inhaled BI-L-239 provided dose-dependent inhibition of the inhaled Ascaris-induced immunoreactive leukotriene C4 release (maximum, 73%; bronchoalveolar lavage [BAL], 20 minutes), late-phase bronchoconstriction (maximum, 41%; +6 to 8 hours), and neutrophil infiltration (maximum, 63%; BAL, +8 hours). In conscious sheep, inhaled BI-L-239 provided dose dependent inhibition of the inhaled Ascaris-induced late-phase bronchoconstriction (maximum, 66%; +6 to 8 hours) and increase in airway responsiveness (maximum, 82%; carbachol, +24 hours). The acute bronchoconstriction was shortened, and neutrophil infiltration diminished (maximum, 61%; BAL, +8 hours) in this model. Finally in conscious actively sensitized guinea pigs pretreated with pyrilamine and indomethacin, inhaled BI-L 239 attenuated acute bronchoconstriction (maximum, 80%; +5 to 15 minutes), leukocyte infiltration (58%; BAL, +3 days) and increase in airway responsiveness (100%; methacholine, +3 days) induced by three alternate-day ovalbumin inhalations. CONCLUSIONS: In conclusion, results in these three animal models indicate that 5-lipoxygenase products may be major contributors to the bronchoconstriction (especially late phase), leukocyte infiltration, and airway hyperresponsiveness that characterize asthma. PMID- 8473682 TI - The effect of time and extraction buffers on residual protein and allergen content of extracts derived from four strains of Alternaria. AB - BACKGROUND: A series of studies was performed to identify optimal elution conditions for production of desired Alternaria allergens with simultaneous reduction of undesired ones. METHODS: Proteins and allergens from four strains of Alternaria extracted for differing time intervals and in different buffers were analyzed by one- and two-dimensional electrophoresis, as well as by immunoglobulin E enzyme-linked immunosorbent assay inhibition and immunoblotting. RESULTS: The amount of protein and carbohydrate released varied with each time interval but was consistent between buffers. Extracts from longer time intervals tended to contain more carbohydrate. Electrophoresis of the four strains demonstrated many similar proteins; however, the concentrations of these proteins showed considerable interstrain difference. Comparison of extraction times for single strains by immunoblotting showed that certain allergens are preferentially released during specific time intervals. Some allergens were seen to be most prevalent in a 24-hour extract, whereas others were most prevalent in a 1-hour extract. Two-dimensional electrophoresis resolved bands into discrete spots. The major shared elements of the four strains could be easily identified. The appearance and disappearance of individual protein elements with time was seen. CONCLUSIONS: Elution conditions have a significant impact on quantities of specific glycoproteins contained in extracts of Alternaria and must be controlled and optimized when such extracts are produced for allergen purification. PMID- 8473683 TI - Increased secretion of tumor necrosis factor-alpha, interleukin-1-beta, and interleukin-6 by alveolar macrophages from patients with sarcoidosis. AB - BACKGROUND: Alveolar macrophages from patients with sarcoidosis were analyzed for their ability to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1-beta), and interleukin-6 (IL-6). RESULTS: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrophages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL 6 only, whereas the constitutive release of IL-1-beta was similar as in healthy volunteers. In vitro stimulation of alveolar macrophages from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose dependent enhanced secretion of TNF-alpha, IL-1-beta, and IL-6. In a similar manner, with corresponding cells from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The data presented indicate that an increased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play a critical part in the pathogenesis of sarcoidosis. PMID- 8473685 TI - Rhinopharyngolaryngoscopy. Upper Airway Allergy Committee. PMID- 8473684 TI - Lol p I-induced IL-4 and IFN-gamma production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season. AB - The reciprocal effects of IL-4 and IFN-gamma on IgE synthesis have been well established. It has also been shown that these two lymphokines are secreted by different subsets of CD4+ T cells (TH1 and TH2), and that TH2 helper T lymphocytes could be involved in the pathophysiology of allergic diseases. But little is known about the effects of an allergen on the profile of lymphokine synthesis by human peripheral blood mononuclear cells (PBMCs) of allergic and nonallergic subjects. We studied the production of IL-4 and IFN-gamma by PBMCs of atopic and nonatopic donors after in vitro stimulation by the group 1 allergen from Lolium perenne pollen (Lol p I), during and out of the grass pollen season. On natural exposure to pollen, Lol p I-induced IL-4 production was observed only with atopic donors (6 of 8), whereas the synthesis of IFN-gamma was observed for all nonatopic donors (7 of 7) and most allergic patients (5 of 7). At the time of the study, higher amounts of IFN-gamma were produced by PBMCs of nonatopic donors than by PBMCs of atopic patients. Out of the pollen season the production of IL-4 was not observed either by atopic (n = 11) or by nonatopic subjects (n = 5). On the other hand, IFN-gamma was produced by PBMCs of most subjects (atopic, 10 of 11; nonatopic, 5 of 5), but at the time of the study no difference was observed between the two groups. These results show that Lol p I induces different profiles of IL-4 and IFN-gamma production by PBMCs of atopic and nonatopic subjects. In atopic subjects this profile of lymphokine synthesis is influenced by the natural exposure to pollen, which is in keeping with the seasonal rise of IgE antibodies. PMID- 8473686 TI - Comparisons of inflammatory responses in IgE-mediated and codeine-induced skin reactions. PMID- 8473687 TI - Gastrointestinal proliferation and aging. AB - The gastrointestinal tract represents an organ system that is characterized by rapid proliferation and by cells that demonstrate differentiation from immature stem cells to terminal differentiated mature cells. Aging gastrointestinal tissues illustrate markedly different phenomena from aged post-mitotic cells. Contrary to generally held prejudices, a state of hyperproliferation, not hypoproliferation, occurs in the epithelial cells of the stomach, the small intestine, and the large intestine of stable-fed, aged rodents when compared to young mature rodents. Furthermore, abnormalities of proliferative and differentiation responses become evident when gastrointestinal tissues are stimulated by injury, or by starvation and refeeding. We speculate that such changes in proliferation and differentiation expose aging gastrointestinal epithelial cells to genotoxic effects that may increase the susceptibility to gastrointestinal cancers. PMID- 8473688 TI - The effect of age on the synthesis of two heat shock proteins in the hsp70 family. AB - Hepatocytes isolated from male F344 rats were exposed to elevated temperatures (40 degrees C to 45 degrees C), and the incorporation of [35S]-L-methionine into proteins was measured from fluorograms of two-dimensional polyacrylamide gels. The synthesis of two proteins was induced by temperatures of 40 degrees C to 42.5 degrees C; however, 45 degrees C inhibited the synthesis of all proteins. Based on their apparent molecular weights and pI values and their recognition by a monoclonal antibody to the HSP70 gene family, the two proteins induced by hyperthermia were found to be the highly heat-inducible hsp70 and the constitutive hsc70. Because a heat shock of 42.5 degrees C for 30 minutes had very little effect on cell viability and induced the synthesis of hsp70 and hsc70, this heat shock was used to study the effect of age on the ability of hepatocytes to respond to the stress of hyperthermia. Neither hepatocytes isolated from young adult (5-7 months) nor old (25-27 months) rats synthesized detectable amounts of hsp70 when incubated at 37 degrees C. However, heat shock induced the synthesis of both hsp70 and hsc70 in hepatocytes isolated from young adult and old rats. The induction of hsp70 synthesis was significantly lower (37%) for hepatocytes isolated from old rats compared to hepatocytes isolated from young adult rats. However, neither the basal level nor the induced level of hsc70 synthesis changed significantly with age. Thus, aging resulted in a decrease in the ability of hepatocytes to synthesize hsp70 in response to hyperthermia; this effect, however, was specific for hsp70. PMID- 8473689 TI - Oxygen-dependent perturbation of life span and aging rate in the nematode. AB - The effects of atmospheric oxygen on the life span and aging rate of the nematode Caenorhabditis elegans were examined. The mean and maximum life spans of both the wild type and mev-1(kn1) mutant, whose cytoplasmic superoxide dismutase activity level is about half of the wild type, were increased and decreased under low and high concentrations of oxygen, respectively. The Gompertz component, a parameter of aging rate, of the wild type was smaller under 1% oxygen than under 2% or more oxygen. Further, the Gompertz component of the mutant increased with an increase in oxygen concentration. These effects of oxygen on the perturbation of life span and aging rate were more pronounced in the mev-1(kn1) mutant than in the wild type. The oxygen-dependent perturbation of life span and aging rate seems to be enhanced by a genetic defect of the mutant in antioxidant defense. A 1% oxygen exposure at the early phase of life span was ineffective for life span extension in the mutant, suggesting that the effect of oxygen concentrations on life span is not secondary to the effects of development and maturation. These results show that changes in oxygen concentration perturb aging rate, and hence oxygen is involved in the specification of life span of the nematode. PMID- 8473690 TI - Dietary restriction retards onset but not progression of leukemia in male F344 rats. AB - The objective of this study was to determine the effect of dietary restriction on the spontaneous occurrence and the progression of leukemia in male F344 rats. The analysis involved both sacrificed rats and those that died spontaneously. These rats had been either ad libitum fed (AL) or restricted to approximately 60% of the ad libitum intake (DR) from 6 weeks of age. Dietary restriction delayed spontaneous death due to this disease by delaying the occurrence of leukemia. However, dietary restriction did not retard its progression, i.e., the time between occurrence and death. PMID- 8473691 TI - Aging as a modulator of respiratory sinus arrhythmia. AB - Aging is associated with an accentuated shift toward sympathetic outflow. Evidence suggests that sympathetic and vagal-cardiac activity change reciprocally. If this hypothesis is correct, then aging would result in an attenuation of vagal-cardiac activity. The current cross-sectional investigation assessed the relationship between aging, vagal-cardiac activity, and arteriolar compliance (AC). Respiratory sinus arrhythmia (RSA) and finger plethysmography, noninvasive measures of vagal-cardiac activity and arteriolar compliance, respectively, were made on 70 normotensive male subjects (age range 15-81 years). Both RSA and AC decreased with age (r = .71 and .89, respectively, p < .001). Analysis of variance revealed significant differences between the six decade groups for RSA and AC (p < .05). These findings support the notion that there is an age-related loss of vagal-cardiac activity that could be partly explained by the loss of arteriolar compliance. These findings are consistent with the hypothesis that there is autonomic nervous system compensation of cardiovascular function in response to an age-related decrease in arteriolar compliance in a normotensive population. PMID- 8473692 TI - Development and validation of a physical performance instrument for the functionally impaired elderly: the Physical Disability Index (PDI). AB - Article describes development of the Physical Disability Index (PDI), an observer administered, performance-based instrument measuring physical disability in frail elderly persons without severe cognitive impairment. Sixty-five items in four subscales encompassing Range of Motion (ROM), Strength (STR), Balance (BAL), and Mobility (MOB) were measured. Subjects were randomly selected frail nursing home residents (N = 103) with a Folstein Mini-Mental State Exam (MMSE) score of > or = 11. Using correlation matrices, cluster analysis, and regression techniques, the scale was reduced to 54 items. All individual item values were standardized and aggregated into subscale and summary PDI scores, each with a range of 0-100. Test retest and interrater reliability were evaluated. Discriminant and convergent validity were established using MMSE, Physical Self-Maintenance Scale (PSMS), and Sickness Impact Profile-Physical Dimension (SIP-PD). PDI is a performance-based instrument that appears to discriminate among frail individuals with differing levels of physical function. Further testing is warranted in other populations of frail-elderly persons to ascertain its applicability and generalizability. PMID- 8473693 TI - Oral health status of the elderly in New England. AB - The New England Elders Dental Study (NEEDS) reports the prevalence, extent and severity of oral diseases and conditions among a representative sample of community-dwelling elders age 70 and older residing throughout the six New England states. In-home, full-mouth examinations were conducted by four calibrated dentists who used National Institute of Dental Research (NIDR) standardized disease measures plus additional diagnostic codes on all tooth surfaces. Only 37.6% of elders age 70 and older were edentulous, while dentate elders had a mean number of teeth per person ranging from 21.5 to 17.9 across age and gender cohorts. The prevalence of untreated coronal decay in elders with teeth was 28% in female elders and 34% in male elders. More than 90% of all elders with teeth had coronal fillings and 22% exhibited untreated root caries. Periodontal destruction was substantial, with 66% of dentate elders exhibiting moderate periodontal pockets (4-6 mm) while 21% exhibited severe periodontal pocketing (> 6 mm). Comparisons with national surveys suggest that periodontal disease prevalence and severity appear to have been underestimated in previous national studies of the elderly. Because of aging and tooth retention trends, the periodontal disease problem of the elderly may be increasing in the face of dentists' tendency to underdiagnose the periodontal diseases, legal constraints on dental hygienists to independently treat them, and inadequate funding for conservative nonsurgical therapies. PMID- 8473694 TI - Thermally-induced cutaneous vasodilatation in aging. AB - A decrease in heat-induced cutaneous vasodilatation has been implicated as the cause of increased heat stress in the elderly. We used laser Doppler techniques to study the skin blood flow response to local heat in 82 healthy volunteers. There were 39 young volunteers, mean age 29 +/- 1, and 43 elderly volunteers, mean age 76 +/- 1. There was minimal difference in skin blood flow at 35 degrees C between the two groups. In contrast, skin blood flow at 44 degrees C was significantly lower in the older subjects at nutritively perfused sites, such as the knee and elbow. However, there was no difference between the young and old groups in skin blood flow at the finger or toe pulp, sites with primarily arteriovenous anastomotic (AVA) flow. In the older subjects, the two components of skin blood flow, microvascular volume (VOL) and red blood cell velocity (VEL), were both decreased at 44 degrees C at nutritive sites, but not at AVA sites. Regression analysis demonstrated a linear fall in blood flow, VOL, and VEL with advancing age at nutritive sites at 44 degrees C. We conclude that thermally induced cutaneous blood flow is reduced in older persons at nutritive capillary sites, but not at AVA sites. PMID- 8473695 TI - The difference in stiffness of the active plantarflexors between young and elderly human females. AB - The purpose of this investigation was to determine the difference in the intrinsic stiffness of the active plantarflexor muscles between young and elderly human females, and to determine changes in this stiffness associated with a 6 week strengthening exercise program. Intrinsic muscle stiffness was determined by measuring the resistance in the first 62 milliseconds offered by the muscle to multiple single stretch trials at 20% to 60% of maximal isometric contraction. Stiffnesses were related to pre-stretch torque (K/PST) by a linear fit. The K/PST relationship of the elderly subjects exhibited a steeper slope, indicating a greater increase in stiffness with an increase in pre-stretch torque. The effect of testing subjects at identical relative, but different absolute pre-stretch torque levels precluded definitive conclusions on possible stiffness differences between the age groups. After the strengthening exercise program, the plantarflexors showed an increase in maximum produced torque, and a decrease in stiffness as well as a decrease in the slope of the K/PST relationship. PMID- 8473696 TI - Anticipatory postural adjustments in older adults: are changes in response characteristics due to changes in strategy? AB - The purpose of this study was to determine if (a) the aging process directly affects the ability to prepare postural adjustments in advance of voluntary movements, or (b) if aging leads to longer movement times which, in turn, lead to less need for advance preparation of the postural muscles. That is, is velocity a mediating variable between age and lack of postural preparation? Postural and prime mover muscle response characteristics of young (n = 16, age 27 +/- 5 years) and older (n = 16, age 71 +/- 8 years) adults were evaluated in an arm-raising paradigm across many arm movement velocity conditions. Older and young adults did not differ in arm movement velocities. Therefore, observed differences between age groups were directly related to the aging process. Muscle timing and sequencing were affected differentially between age groups depending upon which velocity condition was specified. Age-related differences were found in the timing of two postural muscles: in older subjects the contralateral erector spinae muscles were activated later, relative to the deltoid, than in younger subjects, with fewer older subjects showing preparatory activity. Also, older subjects showed more frequent activation of the quadriceps than young subjects. PMID- 8473697 TI - Life span changes in the verbal categorization of odors. AB - An odor description task was used to explore age-related change in odor perception based on 1.19 million U.S. and Canadian respondents (ages 10-90 years) to the National Geographic Smell Survey. Respondents sampled six microencapsulated odorants and selected 1 of 11 descriptors to characterize each smell. Four odors were characterized by strong consensus endorsement of a single descriptor. This consensus weakened with advancing age, and nonmodal descriptors were endorsed more frequently. Nonmodal responses were neither randomly selected, nor systematically biased across odors. Rather, they showed odor-specific patterns of change. Together, these results suggest a marked change in odor categorization across the life span. Odor descriptor profiles were used to generate age-specific multidimensional scaling maps. Stimulus configurations were stable from the third through fifth decades. Those from the sixth through ninth decades showed major displacements for two odors, and suggest that the sweet dimension of odor quality may be particularly variable with maturation. PMID- 8473698 TI - Prior knowledge and face recognition in a community-based sample of healthy, very old adults. AB - This experiment addressed the effects of prior knowledge on episodic face recognition in a community-based sample of healthy older adults from 75 to 96 years of age (N = 228). Subjects were presented with photographs of public Swedish individuals who attained their fame during the 1930s and 1940s, or during the 1980s. Results indicated an overall deterioration of face recognition performance across age. However, performance was higher with the dated than with the contemporary faces across the entire age range, suggesting that the ability to utilize prior knowledge in the context of face recognition is well preserved in very old age. Finally, a multiple regression analysis indicated that, among a variety of demographic, psychometric, and biological variables, age was the best predictor of face recognition performance. PMID- 8473699 TI - Item and relational processing in young and older adults. AB - The item and relational information framework of memory provided a methodology for an analytical approach to age differences in encoding and retrieval processes. Subjects were given related or unrelated words to sort or rate for pleasantness. Young adults performed better than older adults in free recall, but older adults were able to use both item and relational information as well as young adults. In a second experiment, subjects also sorted or rated a list composed of different numbers of category items. The pattern of free recall and cued recall scores indicated that item and relational information affected the memory performance of both age groups in a similar fashion. By examining memory in terms of item and relational information, it appears that older adults do not have difficulty combining two types of target information during encoding and that the information assists in recall of target items. PMID- 8473700 TI - Age differences in letter and color matching: selective attention or internal noise? AB - We tested healthy young and older adults on a letter-matching task that varied letter identity and letter color (Experiment 1) and on a color matching task that varied letter color and letter identity (Experiment 2). The goal of this investigation was to empirically disentangle the theoretical concepts of internal noise and selective attention. The results from Experiment 1 indicated that both young and older adults exhibited "fast-same" effects for reaction time and "false different" effects for errors, and older adults exhibited a relatively larger "false-different" effect. However, letter color did not affect performance. The data from Experiment 2 indicated that older adults, compared with young adults, evidenced greater interference from "different-similar" letter pairs than "different-dissimilar" letter pairs even though the task was color matching. These data suggest that older adults evidenced greater levels of internal noise, and that this factor may modulate age differences in selective attention. PMID- 8473701 TI - Conservation of energy, uncertainty reduction, and swift utilization of medical care among the elderly. AB - This study examined age differences in the timing of the decision to seek medical care. Two cohorts, one of middle-aged (40 to 55 years, n = 88) and one of older patients (65 and over, n = 80), who sought medical care when symptomatic were interviewed at the time of their visit. Age differences were examined with respect to total delay (the time from first noticing symptoms until calling for care), as well as its two constituent phases: appraisal delay (symptom onset until deciding one was ill) and illness delay (decision one was ill until calling for care). Older persons were expected to be more conserving of physical and psychic resources, and thus quicker in seeking care. The cohort effect was expected to be most visible for symptoms judged to be of uncertain seriousness. The delay results and ancillary findings on reasons given for delay are generally supportive of the hypotheses, with the caveat that the cohort difference also reflects higher levels of avoidance behavior by the middle-aged than by the older subjects. PMID- 8473702 TI - Automatic and effortful memory processes in depressed persons. AB - Clinical lore has held that depression results in memory dysfunction, particularly in older adults. Some believe that memory loss due to depression is indistinguishable from an organic dementia and label such dysfunction pseudodementia. Previous literature has inconclusively supported the relation between depression and memory deficits. This research assessed three groups of subjects: (a) 30 depressed patients, (b) 20 psychiatric controls, and (c) 30 normal controls. Dependent memory tasks were designed to vary along the automatic and effortful memory encoding continuum defined by Hasher and Zacks (1979). Two tasks were designed to be effortful (free recall and paired associates) and two tasks were designed to be automatic (memory for frequency and location). Contrary to predictions, depression was not related to memory deficits. However, post-hoc analyses indicated that psychiatric hospitalization and psychotropic medication had a greater negative impact on memory than did depression. As predicted, age resulted in effortful encoding deficits whereas age resulted in minimal deficits on the automatic tasks. There was no evidence of an interaction between depression and age that would be consistent with the descriptive label of pseudodementia. PMID- 8473703 TI - Pain and depression in the nursing home: corroborating results. AB - The relationship between depressed affect and pain was examined in secondary analysis of data on 408 nursing home residents. Also assessed were cognitive impairment, activities of daily living impairment, quality of social networks, and number of medical diagnoses. Analysis revealed that depressed residents were more likely to have pain, regardless of the presence of cognitive impairment. Multiple regression revealed that depressed affect was predicted by more pain, a greater number of medical diagnoses, and poor quality of the social network. These findings corroborate and extend those from a recent study of nursing home and congregate apartment residents (Parmelee et al., 1991). This corroboration and extension of findings occurred despite differences between the two studies with regard to characteristics of participants (this research included residents with all levels of cognitive impairment, and research by Parmelee et al. excluded those who were too disoriented to respond to questions), type of data collection employed (this research used ratings by professional caregivers whereas research by Parmelee et al. used self-report), and assessment instruments used to tap constructs. PMID- 8473704 TI - Evidence for a preretirement process among older male workers. AB - As part of a preretirement role-exit process, older workers could be expected to reinterpret their situations and report less favorable job attitudes as they approach retirement. Using 4-wave, 9-year (1978-1987) panel data on 1,365 nonretired male workers aged 50-69, attitudes about job tension and fatigue were examined along the dimension of self-reported proximity (time-left) to retirement. Results from pooled time-series analysis showed that men evaluated their jobs as more burdensome when drawing closer to a fixed age for retirement, regardless of age and other factors. This is evidence for a preretirement dynamic, and it encourages the notion that time-left at work organizes the experience of older workers. PMID- 8473705 TI - Poverty among older Americans: the plight of nonmetropolitan elders. AB - Elderly persons in nonmetropolitan areas are more likely to be poor than their metropolitan counterparts, and the gap between them increases with age. This study provides a comprehensive empirical comparison of the nature of income poverty among metropolitan (metro) and nonmetropolitan (nonmetro) elders. Drawing on the 1990 Current Population Survey, we document differences in poverty by age and for various demographic subgroups of the elderly population. These analyses show that poverty rates are higher among nonmetro elders for virtually all demographic subgroups. We estimate logistic regression models to predict the likelihood that elders are poor to separate the effects of population composition from those of nonmetro residence. We find that even after controlling for age, sex, race, marital status, and living arrangements, nonmetro elders are more likely to be poor than those in metro areas. PMID- 8473706 TI - Nativity, acculturation, and economic status: explanations of Asian American living arrangements in later life. AB - Using 1980 Census data, we examined the household and nonhousehold living arrangements for older, unmarried women of Japanese, Chinese, Filipino, and Korean descent, finding substantial variation across ethnic groups. We tested three hypotheses regarding the effects of acculturation, economic status, and nativity/immigration status. The results from our multivariate analyses show that Chinese-origin and Filipino-origin women who are less acculturated are more likely to live with others than those who are more acculturated. Members from each Asian American group who can afford independent living are more likely to purchase their privacy. The most consistent finding shows that older, unmarried Asian American women who have migrated to the United States since 1965 are more likely than similar native-born women to live in a complex household as compared to living alone. PMID- 8473707 TI - Who helps whom in older parent-child families. AB - While previous research has assumed that older persons who live with adult children do so because of their poverty or disability, some recent evidence suggests that many of these extended households primarily benefit the child. This article attempts to provide a better understanding of the relative contributions of parents and adult children who live together through detailed analysis of data from the Survey of Income and Program Participation (SIPP). We find unmarried children tend to benefit more from and contribute less to extended households than married children. Similarly, unmarried parents benefit more from living with children than married parents. Results of logistic regression show that financial need and need for assistance with activities of daily living wre important determinants of coresidence for both unmarried children and unmarried parents. Controlling need, racial and ethnic minorities were more likely to live in extended families than non-Hispanic Whites. PMID- 8473708 TI - Determining the pattern of community care: is coresidence more important than caregiver relationship? AB - Researchers have previously emphasized the importance of kinship tie to explaining the pattern of care received by a disabled elder. For example, it has been argued that spouses are a distinct group of caregivers, i.e., they provide more care with less help from others and experience more stress. However, based on the theory of primary group structures and functions, this study hypothesized that coresidence rather than the kinship tie is more important in determining the pattern of caregiving. When spouses are compared to other coresiding caregivers, patterns of informal care and use of formal services are similar. Variance in amounts of informal care is explained by elder gender and frailty level rather than by caregiver relationship. Similarly, level of frailty was the only important predictor of use of formal services. PMID- 8473709 TI - Joint impairment and self-reported disability in elderly persons. AB - Recent findings indicating that arthritis is a major contributor to disability in elderly persons are based on self-reported diagnostic information. We conducted physical examinations of the joints at baseline on 541 older persons. We then tested a multivariate model of total/generic disability which included respondent group, demographic and chronic disease variables (joint impairment and comorbid conditions), arthritis pain, and psychological status. Hierarchical multiple regression found that the model explained 55 percent (adjusted R2 = .55) of the variance in baseline disability with joint impairment accounting for 15 percent (change in R2 = .15) of the variance. When joint impairment was removed from the model, arthritis pain worked well as a surrogate. Together, these findings strongly support the importance of musculoskeletal disease in explaining disability in the elderly population. PMID- 8473710 TI - Expressions of individuality in cognitively impaired elders. Need for individual assessment and care. AB - 1. Cognitively impaired elders uniquely express their individuality (expressed selfness) despite the effects of the dementing process. 2. Recognizing and attending to expressed selfness has implications for planning nursing care both to meet specific needs and to support existing characteristics and behaviors. 3. With the multiple losses encountered in dementia, supporting expressed selfness accessible to the individual can enhance the quality of the individual's living experience. PMID- 8473711 TI - Cerumen impaction. Prevalence and detection in nursing homes. AB - 1. Many people, including health care professionals, believe that hearing loss is a normal part of aging and that little can be done to improve older adults' hearing. If the staff and physicians believe that hearing loss among nursing home residents is expected due to advanced age, then the likelihood of further evaluation of hearing impairments is minimal. 2. Hearing loss is a serious health problem among the elderly. Social isolation, depression, acting out inappropriately, and paranoia have been related to impaired hearing. Cerumen impaction is a reversible, frequently overlooked cause of a conductive hearing loss. 3. Twenty-five percent of nursing home residents were found to have impacted cerumen. One of the nursing homes in the study differed from the others because no residents had cerumen impaction. This was the only home that employed two nurses who had specialty preparation in gerontological nursing. If that home had been excluded, the impaction rate would have been 34%. PMID- 8473712 TI - Institutional policy: use of restraints in extended care and nursing homes. AB - 1. The percentage of patients restrained on these nursing home and extended care units was 32%, similar to that for other nursing home studies. 2. The archetypical restrained patient was older, new on the unit, had altered thought processes and a high potential for injury, and required extensive nursing care. Typically, the type of restraint a patient wore was a vest posey, on the day shift while in his room. 3. The most frequent rationale given by nurses for applying restraints was to prevent patient falls; however, half the time, this rationale was not charted. 4. Upon examining institutional restraint policy, nurses should be prepared to implement changes in documentation format, provide staff education regarding restraint use and alternatives available, institute a rehabilitative and restorative nursing care and fall prevention program, redesign the physical environment, and designate adequate resources for an effective diversion activity program. PMID- 8473713 TI - Understanding and applying research to your practice. PMID- 8473714 TI - Legal risks of nontraditional nursing care. PMID- 8473715 TI - Cognitively impaired elders. Using research findings to improve nursing care. AB - 1. Cognitive changes may be similar in people with Alzheimer's disease, but each person loses abilities differently, and each individual responds differently to interventions. 2. Assessment of cognitive function is needed in order to design appropriate interventions that will be specific in facilitating independence in cognitively impaired elders. 3. Research findings suggest that functional ability in cognitively impaired elders can be maximized by assessing cognitive abilities and using this information to tailor specific interventions that will facilitate independence. PMID- 8473716 TI - The effects of nefazodone, imipramine and placebo, alone and combined with alcohol, in normal subjects. AB - Nefazodone (200 mg, 400 mg/day) imipramine (150 mg/day) and placebo were administered to 12 normal, healthy volunteer subjects for a period of 8 days each. A measured dose of alcohol was consumed with the drug on day 8. A battery of physiological, psychomotor, cognitive and subjective tests was carried out before drug administration and 2 h after drug administration on days 1, 7, and 8. Nefazodone had little effect on heart rate and blood pressure whereas imipramine increased both heart rate and diastolic blood pressure. Nefazodone 400 mg impaired the critical flicker fusion threshold. Dose-dependent improvements in psychomotor performance (Gibson Spiral Maze) and complex memory performance (learning, pursuit rotor, and visual working memory) were produced by nefazodone while imipramine administration impaired performance on these tasks. Subjective changes in alertness and bodily symptoms were produced by all active compounds. While nefazodone failed to potentiate the sedative-hypnotic (depressant) effects of alcohol, imipramine tended to enhance them for psychomotor performance, memory assessments, and some subjective ratings. Thus, nefazodone, particularly at lower dose levels, causes less disruption of human performance than imipramine. This effect probably reflects the lack of anticholinergic activity of nefazodone. Also, nefazodone failed to potentiate the depressant effects of alcohol, perhaps because of its minimal alpha-blockade. PMID- 8473717 TI - Relationship between antidepressant response and plasma concentrations of fluoxetine and norfluoxetine. AB - The relationship between plasma concentration, clinical outcome and side-effects was examined in 23 patients with major depressive disorder (DSM-III-R) treated with fluoxetine. All patients received a fixed dose of 20 mg for 6 weeks. Good response was observed in 57% of patients, while 30% of patients had moderate responses after 6 weeks of treatment. Fluoxetine and norfluoxetine plasma concentrations were not significantly influenced by age and sex. At 6 weeks, plasma fluoxetine concentrations were not significantly different between responders and non-responders to treatment (82.2 +/- 59.6 micrograms/l vs. 84.7 +/- 6.7 micrograms/l) or those with or without side-effects (74.6 +/- 28.7 micrograms/l vs. 87.0 +/- 66.6 micrograms/l). Similarly, norfluoxetine concentrations were not significantly different for responders and non-responders (65.5 +/- 28.9 micrograms/l vs. 66.5 +/- 26.2 micrograms/l) or those with or without side-effects (66.6 +/- 14.4 micrograms/l vs. 61.5 +/- 33.6 micrograms/l). Plasma concentrations and clinical outcome were not related in a simple manner. Further studies are needed to evaluate the role of monitoring plasma fluoxetine/norfluoxetine concentrations as a routine procedure. PMID- 8473718 TI - A pharmacological comparison of citalopram, a bicyclic serotonin selective uptake inhibitor, with traditional tricyclic antidepressants. AB - Major depressive disorder is a very common and a very serious illness that not only disrupts the lives of the people with the condition but also the lives of their families. Effective identification and treatment of those with this disease would greatly improve the lives of a very sizeable proportion of the people of the world. Numerous drugs have been introduced since the 1950s that have proven to be useful in the therapy of major depressive disorder patients but these compounds typically have unwanted side effects due to their actions on many different aspects of brain function. Citalopram, one of the more recently developed antidepressant drugs, is a selective inhibitor of the transport of the neurotransmitter serotonin into nerve terminals and other cells that accumulate serotonin. Citalopram does not affect the uptake of other neurotransmitters nor does it have affinity for the receptors of any neurotransmitter. It is as effective therapeutically as the older antidepressants but it produces considerably fewer side effects than the traditional antidepressants such as amitriptyline. Citalopram appears to have minimal effects on the cardiovascular system and to be one of the few antidepressants to be eliminated to any extent by the kidneys. These characteristics may be an advantage in treating elderly patients with major depressive disorder, or those patients unable to tolerate the anti-cholinergic side effects of the traditional antidepressants. PMID- 8473719 TI - Differential effects of lorazepam and oxazepam on priming. AB - The effects of lorazepam (2 mg), oxazepam (30 mg) and placebo on performance in implicit and explicit memory tasks were compared in a double-blind, independent group study with 36 healthy volunteers. Both benzodiazepines (BZs) impaired performance on the explicit task (free recall). However, only lorazepam impaired performance of the implicit task (word-stem completion). A similar pattern of drug effects was observed on a secondary task which used different instructions at stimulus presentation. BZ effects on the explicit task were more associated with levels of sedation (indexed by finger tapping speed) than their effects on the implicit task. It is concluded that both BZs impair episodic memory but only lorazepam impairs priming. PMID- 8473720 TI - The effects of moclobemide on psychomotor performance and cognitive function. AB - Sixteen young male volunteers received single doses of moclobemide 200 mg, moclobemide 400 mg, amitriptyline 50 mg and placebo in a double-blind crossover study. Subjects then completed a test battery which is sensitive to the effects of psychoactive drugs at 1, 2, and 4 h post-dose. The test battery included tasks of choice reaction time, tracking, critical flicker fusion threshold and memory scanning. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). The results show that the positive internal control (amitriptyline) has a sedative effect in that it increased critical flicker fusion threshold, reaction time and tracking error. Moclobemide 400 mg increased reaction time in the tracking task but neither dose of moclobemide impaired psychomotor performance or cognitive ability in any of the other tests. PMID- 8473721 TI - The prolactin response to d- and l-fenfluramine and to d-amphetamine in human subjects. AB - Twelve normal male volunteers took part in a double-blind placebo-controlled study to measure the effects of d- and l-fenfluramine singly and in combination with d-amphetamine on plasma prolactin levels. Both isomers of fenfluramine were found to differ significantly in their effects from d-amphetamine, and from placebo, causing prolactin levels to rise. d-Fenfluramine produced the greatest change. There were minor differences between the level of activity of the two drugs when given in conjunction with d-amphetamine. d-Amphetamine produced a non significant reduction in prolactin secretion. The neurochemical basis for the experimental findings reported is considered, with special reference to the use of d-fenfluramine as a specific serotonergic probe. PMID- 8473722 TI - The loss of appetite during depression with melancholia: a qualitative and quantitative analysis. AB - The loss of appetite occurring severe depression was investigated with an experimental method comparing the eating behaviour of 12 melancholic inpatients to 12 matched normal controls. Food intake and appetite, divided into more basic components such as desire to eat, hunger, satiety, prospective food consumption and pleasure from eating, were monitored during a test meal. Patients ate less than controls, but the difference was not significant. The pattern resulting from the temporal tracking of the appetite ratings indicated that patients were disturbed at the beginning of the meal and showed a decreased desire to eat, hunger and prospective food consumption and an increased satiety and that their pleasure from eating was diminished. These findings suggest that the loss of appetite induced by melancholia follows a specific pattern. PMID- 8473723 TI - Seizures induced by combined levomepromazine-fluvoxamine treatment. AB - We report a case of combined levomepromazine-fluvoxamine treatment-induced seizures. It seems that combined treatment of fluvoxamine with phenothiazines may possess proconvulsive activity. PMID- 8473724 TI - Clozapine-lithium combined treatment and agranulocytosis. AB - A case report of clozapine-induced agranulocytosis in a patient treated concomitantly with lithium is reported. The possible role of lithium in the mechanism of clozapine myelosuppression is discussed. PMID- 8473725 TI - Psychosis following readministration of diethyl proprion: a possible role for kindling? AB - The case of an organic psychosis following the readministration of an amphetamine like anorexiant is described. Previous therapeutic use of the same drug 2 years earlier was without adverse effect. Similar phenomena have been reported with other drugs, and both behavioural sensitization and kindling are possible explanations. The latter, however, provides a parsimonious explanation, a therapeutic rationale, and brings together seemingly disparate laboratory and clinical phenomena. PMID- 8473726 TI - Class II-restricted presentation of a hen egg lysozyme determinant derived from endogenous antigen sequestered in the cytoplasm or endoplasmic reticulum of the antigen presenting cells. AB - A cDNA encoding a form of hen egg lysozyme (HEL) lacking a leader sequence and predicted to be localized in the cytoplasm, was transfected into MHC class II positive B lymphoma cells. Cytoplasmically expressed HEL (cytHEL) had a half-life of less than 5 min and did not react with HEL specific mAb suggesting non-native conformation. Cells expressing cytoplasmic HEL, as well as cells previously reported to express a low level of HEL retained in the endoplasmic reticulum (ERHEL), constitutively presented the HEL determinant encoded by residues 46-61 to a sensitive class II-restricted T hybridoma (3A9). Constitutive presentation of HEL determinants was not detectable in cytHEL or ERHEL transfectants using T hybridomas with lower sensitivity to exogenous Ag. Constitutive presentation of HEL46-61 derived from cytoplasmic HEL was demonstrable in multiple transfected clones and was most obvious when a CMV rather than SV40 promoter was used to express the cytHEL gene. The presentation of HEL46-61 by cytHEL transfectants was not due to HEL reuptake by bystander cells because there was no biochemical evidence of cytHEL shedding and cytHEL supernatants added to indicator APC did not result in HEL46-61 presentation. Constitutive presentation of endogenous HEL46-61 by the cytHEL and ERHEL transfectants was inhibited by chloroquine, and recovery of presentation of endogenous HEL was slower in cytHEL compared with ERHEL transfectants. The findings indicate that class II-restricted presentation of Ag retained in the cytoplasm or endoplasmic reticulum does take place but probably requires abundant levels of intracellular Ag and is easily disrupted by lysosomotropic agents. These pathways of presentation may be important when high levels of foreign endoplasmic reticulum-retained or cytoplasmic Ag are present (e.g., viral infection), and during the acquisition of self-tolerance by highly sensitive developing T cells. PMID- 8473727 TI - An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. AB - Langerhans cells (LC) are Ag-presenting cells required for induction of primary immune responses in skin. After activation by Ag, LC express increased levels of MHC class II Ag, exhibit increased accessory cell activity, and migrate to regional lymph nodes where they stimulate T cells. One of the earliest manifestations of LC activation is the accumulation of increased amounts of IL-1 beta mRNA in LC within 15 min after exposure to contact allergens in vivo. To determine if enhanced IL-1 beta production by LC could be causally linked to epicutaneous sensitization, we injected IL-1 beta intradermally into the ears of BALB/c mice and extracted total epidermal RNA 4 h later. A quantitative reverse transcriptase-polymerase chain reaction technique was used to compare changes in IL-1 alpha, IL-1 beta, macrophage inflammatory protein 2, IL-10, TNF-alpha, and 1 A alpha chain mRNA signals caused by intradermally-injected IL-1 beta to those caused by intradermal IL-1 alpha or TNF alpha, or by topical application of the contact allergen trinitrochlorobenzene (3% TNCB). Intradermal injection of 25 ng IL-1 beta resulted in 5-to 100-fold enhancement of mRNA signals for IL-1 alpha, IL-1 beta, MIP-2, IL-10, TNF alpha, and class II I-A alpha, mimicking the changes caused by allergen. In contrast, injection of equivalent amounts of IL-1 alpha or TNF alpha did not significantly alter the epidermal cytokine pattern. Simulating the effects of topically applied TNCB, intradermally-injected IL-1 beta (but not IL-1 alpha or TNF alpha) also caused enhancement of LC MHC class II expression. In addition, LC derived from IL-1 beta-injected skin were 2 to 3 times more potent accessory cells in an anti-CD3 proliferation assay than LC from IL-1 alpha or sham-injected skin. Finally, injection of hamster anti-mIL-1 beta mAb into the skin prior to TNCB treatment completely prevented sensitization to this allergen, although injections of similar amounts of hamster anti-mIL-1 alpha mAb or PBS were without effect. Taken together, our data indicate that dendritic cell derived IL-1 beta may be a critical molecule required for initiation of primary immune responses in skin. PMID- 8473728 TI - Aberrant induction of T cell tolerance in B cell suppressed mice. AB - Self-tolerance is the process by which the T cell repertoire develops without expressing self-reactive specificities. The mechanisms which functionally eliminate self-reactive T cells are clonal deletion and clonal inactivation, and both of these phenomena have been studied in T cell populations reactive to endogenous superantigens that are encoded by endogenous mouse mammary tumor proviruses (Mtv). The studies described here demonstrate that the kinetics of Etc 1 (encoded by the Mtv-9 open reading frame gene)-mediated deletion are much slower than that seen for Mls 1a (encoded by the Mtv-7 open reading frame), and that Etc-1-reactive T cells are present in the periphery up to 2 wk after birth. The deletion of peripheral Etc-1-reactive T cells late in ontogeny indicates an efficient mechanism of peripheral clonal deletion in these animals. The clonal deletion of Etc-1-reactive cells is abrogated in B cell-suppressed animals; however, clonal elimination of peripheral V beta 5+ or V beta 11+ (Etc-1 reactive) T cells can be induced when these mice are allowed to recover their B cell population after cessation of anti-mu treatment. Finally, we establish that peripheral Etc-1-reactive V beta 11+/CD4+ T cells remaining in B cell-suppressed and recovering animals are markedly less responsive to stimulation through the TCR than are control T cells. These data support the idea that peripheral self reactive T cells can be rendered tolerant by two mechanisms which may be temporally related. This model suggests that clonal hyporesponsiveness may be followed by clonal deletion. PMID- 8473729 TI - Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. I. Inhibition by RP-3 treatment of the priming and effector phases of delayed type hypersensitivity to sheep red blood cells in rats. AB - Recent studies on neutrophils have revealed that these cells produce various cytokines, and may be involved in regulation of the immune response. We examined whether neutrophils are involved in delayed type hypersensitivity (DTH) to SRBC in rats by selective depletion of in vivo neutrophils using a mAb designated RP 3. When the rats had been treated with RP-3 at the time of priming with SRBC, DTH to these cells was inhibited. Furthermore, RP-3 treatment was effective in inhibiting the effector phase of the DTH response to SRBC. When spleen cells from rats that had been treated with RP-3 at the time of immunization were used for local transfer of DTH, footpad swelling was significantly less than that induced by spleen cells from the RP-3-untreated immune rats. PMID- 8473730 TI - Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. II. Inhibition by RP-3 treatment of mononuclear leukocyte recruitment in delayed-type hypersensitivity to sheep red blood cells in rats. AB - We demonstrated in our previous paper that treatment of rats with RP-3, a mAb that depletes in vivo neutrophils selectively, resulted in inhibition of both the priming and effector phases of delayed type hypersensitivity (DTH) to SRBC. In order to clarify the mechanisms of this phenomenon, we examined the effect of RP 3 treatment on mononuclear leukocyte (MNL) recruitment in DTH. When rats had been treated with RP-3 at the time of Ag priming, MNL migration, which accompanies DTH, was inhibited. The prior infiltration of neutrophils was also partially required for MNL recruitment because migration was inhibited when the immune rats were treated with RP-3 at the time of DTH elicitation. PMID- 8473731 TI - Cross-linking of B cell receptor-related MB-1 molecule induces protein tyrosine phosphorylation in early B lineage cells. AB - Cross-linking of surface B cell Ag receptor (BCR) induces tyrosine phosphorylation of BCR-associated components through a receptor-mediated signal transmission pathway. B cell-specific mb-1 and B29 genes encode the alpha/beta components of the BCR-associated complex in mature sIgM+ B cells. Here, we studied the involvement of the mb-1 gene product, MB-1, in the BCR-related structure of immature B cells. Affinity-purified anti-MB-1 antibody coprecipitated mu chain/20-kDa/15-kDa proteins together with monomer MB-1 and Ig alpha/Ig-beta heterodimer components from digitonin lysates of the pre-B cell line 18.81. The monomer MB-1 and Ig-alpha in the pre-B cell line were shown to migrate with identical patterns in nonequilibrium pH gradient gel electrophoresis/SDS-PAGE. Western blot analysis showed that MB-1 protein is coprecipitated with mu chain from the pre-B cell line. We studied the tyrosine phosphorylation response of bone marrow B lineage cells as well as spleen B cells after cross-linking of BCR-related components with anti-mu, anti-kappa, and anti MB-1 antibodies. We identified the activation of tyrosine kinase by direct cross linking of MB-1 expressed on the surface of early B lineage cells. Anti-mu antibody stimulation induced the activation of tyrosine kinase in early (5- to 10 min) and late (30- to 120-min) responses in bone marrow early B lineage cells. Anti-MB-1 mAb (11-18-5) induced the late response exclusively but anti-kappa antibody induced only the early response. These results clearly indicate that MB 1 acts in the BCR-mediated signal transmission in early B lineage cells. To explore the molecular mechanism of protein tyrosine phosphorylation in bone marrow B lineage cells, we studied associated components of the BCR complex by using an in vitro kinase reaction and observed the phosphorylation of a 60-kDa protein in pre-B cell lines. The 60-kDa phosphoprotein coprecipitated with MB-1 and the BCR-related complex is very similar to the Src-type Fyn tyrosine kinase or a Fyn-related protein. PMID- 8473732 TI - Acquired resistance to superantigen-induced T cell shock. V beta selective T cell unresponsiveness unfolds directly from a transient state of hyperreactivity. AB - TCR V beta selective T cell activation and systemic release of T cell-derived lymphokines causing lethal shock in D-galactosamine (D-Gal)-sensitized mice depicts only one facet of in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB). An immediate second major aspect represents the induction of peripheral unresponsiveness in SEB-reactive V beta 8+ T cells. SEB causes in vivo within 4 h resistance to an otherwise lethal challenge with SEB plus D-Gal, as well as to a challenge with the heterologous ligand toxic shock syndrome toxin 1 plus D-Gal. Contrary to the first challenge, no serum-borne IL-2 and TNF are discernible during the second challenge. On the other hand, kinetic analyses in vitro of LN cells draining the site of the first in vivo challenge indicate that SEB-reactive T cells develop via a transient state of hyperreactivity into a profound state of ligand-specific unresponsiveness. Yet unresponsive V beta 8+ T cells express IL-2R and are responsive to the growth-promoting effect of IL-2. Cyclosporin A does not impair sequential induction of hyperreactivity and unresponsiveness with concomitant IL-2R expression, but effectively blocks systemic IL-2 and TNF release during the initial hyperreactive phase. Taken together, the in vitro data imply that ligand-specific hyperreactivity followed immediately by ligand-specific unresponsiveness represents a hallmark of in vivo challenge with the superantigen SEB. The in vivo data suggest the existence of additional suppressive elements masking the ligand specificity of the state of unresponsiveness induced by SEB. PMID- 8473733 TI - Profound deletion of mature T cells in vivo by chronic exposure to exogenous superantigen. AB - It has been noted previously that superantigens can under different circumstances stimulate activation, expansion, anergy, and/or deletion of reactive T cells in vivo and in vitro. Here, we present a detailed examination of the expansion and deletion of T cells in vivo in response to the superantigens staphylococcal enterotoxin A (SEA) in the B10.BR mouse. Mice were either acutely or chronically exposed to varying doses of SEA, and the relative level of T cells bearing SEA reactive V beta elements was followed over time in lymphocytes purified from peripheral blood, lymph nodes, mesenteric lymph nodes, and spleen. In most cases, an initial sharp rise in the proportion of reactive T cells was followed by a dramatic decline. Cells of the CD4+ and CD8+ lineages displayed subtle differences in their kinetics of activation and deletion, as well as their sensitivity to different doses of SEA. Furthermore, cells bearing either of two V beta elements previously characterized as SEA-reactive showed some differences in their responses to SEA treatment. Acute exposure usually caused the disappearance of only 50% to 70% of reactive T cells; however, chronic exposure to SEA caused almost complete deletion of target T cells. Deletion was evident even in animals treated with very low doses of SEA, doses that were too small to cause any apparent T cell proliferation. Thus, proliferation does not appear to be a prerequisite for peripheral deletion of T cells. PMID- 8473734 TI - Strain-dependent leakiness of mice with severe combined immune deficiency. AB - Mice with immunodeficiency provide an excellent in vivo model for cell transfer experiments. In this study, we compare the extent of immune deficiency of the original CB17 severe combined immune-deficient (SCID) mice with that of two other strains of immune-deficient mice, the recently developed C3H SCID mice and the beige/nude/X-linked immune-deficient (BNX) mice. Detectable levels of serum lg (higher than 0.4 microgram/ml) were found in 79% of CB17 SCID mice studied (n = 24) and in all BNX mice (n = 12); some leaky CB17 SCID mice had normal levels of Ig. In contrast, only 15% of C3H SCID mice (n = 61) had detectable serum lg; the highest Ig level in this strain was 9.6 micrograms/ml. Age had no effect on serum Ig concentrations of C3H SCID mice; in contrast, all old (> 1-year-old) CB17 SCID mice studied had detectable levels of serum Ig. Transfer of syngeneic, normal, neonatal thymocytes increased serum Ig of SCID mouse origin to near-normal levels in all CB17 SCID mice but had no effect on serum lg concentrations in C3H SCID mice. Treatment with anti-asialo-GM-1 antiserum to abrogate NK cell activity increased serum Ig levels in 37% of CB17 SCID mice but had no effect on Ig production in C3H SCID mice. Flow cytometric analysis failed to identify mature T or B cells in C3H SCID mice; in contrast, some leaky CB17 SCID mice had detectable numbers of T and B cells in the peritoneal cavity. After immunization with bacteriophage phi X 174, neither C3H nor CB17 SCID mice, including leaky mice, produced specific antibody to phage. In contrast, BNX mice produced small but significant amounts of anti-phage antibody. These results indicate that, of the three strains of immune-deficient mice, C3H SCID mice have the most severe immune defect. We predict that C3H SCID mice will be best suited for cell transfer experiments. PMID- 8473735 TI - Photoaffinity labeling of the T cell receptor on living cytotoxic T lymphocytes. AB - Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of an antigenic peptide with MHC class I molecules and the TCR on living cells. Two photoreactive derivatives of the H-2Kd (Kd) restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) were used. The first derivative contained an N-terminal photoreactive iodo, 4-azido salicyloyl (IASA) group and biotin on the TCR contact residue Lys259 [IASA YIPSAEK(biotin)I]. As previously described, this derivative selectively bound to and labeled the Kd molecule. The second photoreactive compound, the isomeric biotin-YIPSAEK(IASA)I, also efficiently bound to the Kd molecule, but failed to label this protein. A CTL clone derived from a mouse immunized with this derivative recognized this conjugate but not the parental P. berghei circumsporozoite peptide or the [IASA-YIPSAEK-(biotin)I] derivative in an Kd restricted manner. Incubation of the cloned CTL cells with biotin-YIPSAEK(IASA)I, but not its isomer, followed by UV irradiation resulted in photoaffinity labeling of the TCR-alpha chain that was dependent on the conjugate binding to the Kd molecule. The TCR labeling was partially inhibited by anti-LFA 1 and anti-ICAM1 mAb, but was increased by addition of beta 2m or soluble KdQ10. The exquisite labeling selectivity of the two photoprobes opens a new, direct approach to the molecular analysis of antigen presentation and recognition by living CTL. PMID- 8473736 TI - p21ras function is important for T cell antigen receptor and protein kinase C regulation of nuclear factor of activated T cells. AB - In T cells, signals initiated at the TCR, and in particular activation of protein kinase C (PKC), can activate the p21ras proteins. Triggering of the TCR and PKC is required for the efficient production of the T cell growth factor, IL-2. IL-2 gene transcription is controlled by a 275-bp enhancer that is known to contain binding sites for many transcription factors including the octamer family of proteins, NF kappa B, AP-1, and a T cell-specific factor, NFAT (nuclear factor of activated T cells). NFAT binds to a region of the IL-2 enhancer that has been defined as a TCR response element (ARRE-2), and is induced in response to increases in intracellular calcium, stimulation of PKC, or triggering of the TCR. To determine whether p21ras is involved in the signals that regulate NFAT, we examined the effect of expression of a constitutively active p21ras mutant, v-Ha ras, and a dominant inhibitory mutant of p21ras, c-Ha-ras(asn)17, on the induction of a NFAT-driven reporter gene (NFAT CAT) during T cell activation. The constitutively active Ras mutant could synergize with the calcium ionophore ionomycin to induce NFAT. In addition, expression of p21v-Ha-ras could enhance NFAT CAT induction in response to TCR and PKC agonists. The dominant inhibitory mutant of p21ras could prevent NFAT CAT expression in response to PKC or TCR triggering. These data show that Ras regulates NFAT, and that p21ras function is important for the TCR- and PKC-regulated pathways that regulate NFAT. PMID- 8473737 TI - Differential nuclear expression of enhancer A DNA-binding proteins in human first trimester trophoblast cells. AB - In order to investigate the possible molecular regulatory mechanisms that repress classical HLA class I and stimulate nonclassical HLA-G and E-class I gene transcription in human trophoblast cells, we searched for the nuclear expression of the enhancer A DNA-binding proteins of the KBF1/NF-KB/rel family. Using both purified extravillous cytotrophoblast and villous syncytiotrophoblast from first trimester human placenta, it appeared that members of this family were present in the cytotrophoblast and absent in the syncytiotrophoblast. First, using the double stranded enhancer A DNA nucleotidic sequence that contains the palindromic KB site, known to be the binding site of the p50 subunits of KBF1-NF-KB and c-rel factors, we demonstrated, by band-shift assay, that binding activity, inhibited by addition of anti-p50 polyclonal serum, was present in cytotrophoblast as well as control maternal decidual cells, embryonic fibroblasts, and the trophoblast derived JAR cell line. In contrast, this DNA-protein complex was undetectable in syncytiotrophoblast nuclear extracts. The specificity of this protein-DNA complex was further demonstrated by its disappearance upon competition with an excess of cold homologous nucleotidic competitor. Other nucleoprotein complexes were also detected in all nuclear extracts, including syncytiotrophoblast, that were competed out by an excess of cold enhancer A competitor DNA but were not affected by the addition of anti-p50 or anti-NF-KB sera, suggesting the presence of additional enhancer A-binding factors different from the KBF1/NF-KB/rel family. Second, using a Western immunoblot analysis, a doublet around 85 kDa was specifically stained by the same anti-p50 serum in cytotrophoblast, maternal decidual cells, embryonic fibroblasts, and the JAR nuclear extracts whereas no signal was obtained in syncytiotrophoblast. Finally, immunofluorescence cell staining using the same anti-p50 serum showed a positive staining in both cytoplasm and nucleus of cytotrophoblast and its absence in syncytiotrophoblast. We hypothesize that this enhancer A DNA-binding factor might represent the c-rel trans-acting factor, related to p50/KBF1/NF-KB proteins, and we discuss its possible relevance to the HLA class I transcription in human tissues. PMID- 8473738 TI - Isolation and characterization of a novel B cell activation gene. AB - Using subtractive cDNA cloning, we have isolated a series of cDNA clones that are differentially expressed between B and T lymphocytes. Whereas some of the isolated cDNA are from known B cell-specific genes, many of them represent previously uncharacterized genes. One of these unknown genes was denoted as BL34. Northern blot analysis performed with the BL34 cDNA revealed a 1.6-kb mRNA transcript that was present at low levels in RNA extracted from resting B lymphocytes, but whose expression was markedly increased in RNA prepared from mitogen-activated B cells. Similarly, RNA prepared from several B cell lines treated with phorbol myristate acetate (PMA) contained high levels of BL34 mRNA. In contrast, RNA from purified T cells treated with phytohemagglutinin and PMA had undetectable amounts of BL34 mRNA. In addition, high levels of BL34 mRNA were detected in RNA purified from PBMC of a patient with B cell acute lymphocytic leukemia. Southern blot analysis of human DNA from various tissues and cells lines demonstrated that BL34 is a single-copy gene without evidence of rearrangement. Two full length BL34 cDNA were sequenced, and an open reading frame of 588 bp was identified that was predicted to encode for a 196 amino acid protein. Searches of several protein data bases failed to find any homologous proteins. To directly analyze the expression of BL34 mRNA in lymphoid tissues in situ, hybridization studies with human tonsil tissue sections were performed. BL34 mRNA was detected in a portion of the cells in the germinal center region and adjacent to the mantle region. Further characterization of the BL34 gene and its protein should lead to insights to its role in B cell function and the consequences of its over-expression in acute lymphocytic leukemia. PMID- 8473739 TI - The role of viral enhancer "core" motif-related sequences in regulating T cell receptor-gamma and -delta gene expression. AB - T cells express clonally distributed alpha beta or gamma delta Ag receptor heterodimers. Transcriptional enhancers for the genes of all four subunits are active in both gamma delta and alpha beta T cells, but are less active or inactive in other cells. Conserved sequence motifs are present in all four enhancers, suggesting that common transcription factors regulate TCR gene expression. One of these motifs in the gamma 3 site of the TCR-gamma enhancer is similar to motifs found in several other lymphoid-specific and viral enhancers. This conserved "core" sequence is present in the enhancers of Moloney and SL3-3 murine leukemia viruses, important for transcription in T cells and in determining disease specificity. Here we characterize the gamma 3 site of the gamma enhancer and a corresponding homologous site, delta E3, of the TCR-delta enhancer. Our results suggest that the core site is critical for activity of the 200-bp gamma enhancer fragment and of the gamma 3 and delta E3 sites. Furthermore, we identify a nuclear factor in human T cell lines that specifically binds the core region in these and several other core-containing enhancers. This factor may be identical to or related to a purified bovine nuclear core binding factor that binds the core region of the Moloney murine leukemia virus enhancer, gamma 3 and delta E3 sites, suggesting that similar proteins regulate the TCR gamma, delta and Moloney murine leukemia virus enhancers. Other sequences in the gamma 3 site upstream of the core sequence are also critical for activity in T cells, suggesting that at least two different factors are required for functional activity of the gamma 3 site. PMID- 8473740 TI - Autoantibodies in Chagas' disease. An antibody cross-reactive with human and Trypanosoma cruzi ribosomal proteins. AB - Sera from 102 patients with chronic Chagas' disease were studied for the presence of autoantibodies to intracellular proteins and nucleic acids by three different methods. Only four sera had autoantibodies detected by indirect immunofluorescence on HEp-2 cells. All of the sera were negative for anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm and anti-RNP autoantibodies but 12 (12%) of the sera had low to moderate levels of anti-histone antibodies. When Chagas sera were tested for autoantibodies to a total HeLa cell extract by Western blotting, weak reactivity was observed in 31 sera. Despite significant heterogeneity in the protein Ag targeted by these sera, seven recognized a 23-kDa protein. Strong binding to this 23 kDa protein was observed in one-third of the sera when isolated ribosomes were used as source of Ag. In contrast, no autoreactivity was detected with ribosomal proteins P0, P1, and P2. These findings confirm the presence of autoantibodies in chronic Chagas' disease and indicate a remarkable restricted humoral immune response to human ribosomal proteins. Furthermore, affinity-isolated anti-23-kDa antibody cross-reacted with a Trypanosoma cruzi ribosomal protein of similar molecular weight. This molecular mimicry may be responsible for the apparent breakdown of self-tolerance resulting in tissue damage. Indeed, experiments demonstrating that immunization of mice and rabbit with T. cruzi ribosomes have been reported to induce myocarditis. PMID- 8473741 TI - IL-2 is necessary for the progression of leishmaniasis in susceptible murine hosts. AB - BALB/c mice are highly susceptible to disseminated infection with the intracellular protozoa Leishmania major. Progression of disease requires in vivo expansion of Th2 CD4+ lymphocytes and is reversed by treatment with anti-IL-4 monoclonal antibody. Inasmuch as IL-2 may be necessary for both the production of IL-4 and differentiation of Th2 cells, the possible contribution of IL-2 to progressive infection was examined. Four weekly injections of anti-IL-2 mAb (S4B6) cured more than 80% of BALB/c mice infected with L. major, as determined by diminished footpad swelling and decreased numbers of parasites in infected tissues. Multiple doses of S4B6 were necessary for benefit; a single dose given at the time of infection was ineffective. The anti-IL-2R mAb PC61 demonstrated a similar protective effect when administered twice weekly for 4 wk. Anti-IL-2 mediated cure of cutaneous leishmaniasis was associated with increased IFN-gamma and decreased IL-4 production by regional lymph node cells compared to untreated BALB/c mice with progressive illness. Both CD4+ and CD8+ T lymphocytes contributed to the increased expression of IFN-gamma mRNA in cured mice. These data suggest that levels of IL-2 suboptimal for Th2 expansion in vivo do not inhibit Th1 CD4+ and CD8+ T cell activation and IFN-gamma synthesis. Other cytokines or activation pathways that are either IL-2-independent or synergistic with low levels of IL-2 may account for the appearance of curative T cell responses during treatment with anti-IL-2 antibodies. PMID- 8473742 TI - Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic human filariasis. AB - A population of 164 adult individuals resident in an area endemic for Brugia malayi lymphatic filariasis has been studied for humoral immune responses to filarial parasites. Antibody levels to Ag extracted from adult worms were determined for each of the IgG subclasses, for IgM and for IgE. The dominant isotype of antifilarial antibody was IgG4, which represented 88% of total IgG in asymptomatic microfilaremics, most of whom possessed 100 to 1000 micrograms/ml of specific antibody of this subclass (geometric mean 762 micrograms/ml). Patients with chronic disease (elephantiasis), who were generally amicrofilaremic, had substantially higher levels of IgG1, IgG2, and IgG3, but a 3.4-fold lower geometric mean level of specific IgG4 (222 micrograms/ml) than asymptomatics with or without microfilaremia. In contrast, specific IgE antibody levels in cases of elephantiasis were on average 4.5 times higher than those found in the asymptomatic carrier state. The majority of microfilaremics were therefore typified by extremely high specific IgG4 concentrations and relatively low IgE reactivities, whereas clinical cases tended to show the reverse relationship. The possible roles of these isotypes and the implications of changing IgG4/IgE balances in disease are discussed. PMID- 8473743 TI - Ity influences the production of IFN-gamma by murine splenocytes stimulated in vitro with Salmonella typhimurium. AB - The Ity-Lsh-Bcg genetic locus in the mouse has been documented to confer innate resistance to at least three intracellular pathogens: Salmonella typhimurium, Leishmania donovani, and Mycobacterium. Expression of the resistance gene(s) results in a slower net growth of these pathogens in the reticuloendothelial system early postinfection. Although it is clear that the resident macrophages in resistant mice are functionally superior with regard to antimicrobial activity, the exact mechanism(s) underlying the control exerted by this gene is not understood. Using S. typhimurium infection as a model, we have examined the influence of this resistance gene(s) on the production of IFN-gamma, a cytokine known to play an important role in host-defense against several intracellular pathogens. We compared IFN-gamma production by splenocytes from resistant (Ity(r)) and sensitive (Ity(s)) inbred mouse strains after stimulation in vitro with S. typhimurium. Spleen cells from Ity(r) mouse strains produced significantly higher levels of IFN-gamma when compared to spleen cells obtained from Ity(s) mouse strains. Enhanced IFN-gamma production was not a generalized response to bacteria. Listeria monocytogenes induced comparable levels of IFN gamma production from both Ity(r) (CBA/J) and Ity(s) (C57BL/6) mice. Splenocytes from Ity congenic mouse strains displayed similar differences in the level of IFN gamma produced after S. typhimurium stimulation, with spleen cells from the Ity(r) strain producing significantly higher levels of IFN-gamma when compared to spleen cells from the Ity(s) strain. A requirement for adherent cells and/or adherent cell-derived factors has been documented for IFN-gamma production by S. typhimurium-stimulated splenocytes. Interestingly, supernatant from adherent cells obtained from Ity(r) mouse strains was found to induce the production of significantly higher levels of IFN-gamma when compared to adherent cell supernatant from Ity(s) strains. Nylon wool nonadherent cells from Ity(s) mouse strains produced high levels of IFN-gamma when exposed to supernatants obtained from adherent cells of Ity(r) mouse strains. In contrast, nylon wool nonadherent cells from Ity(r) mouse strains produced reduced levels of IFN-gamma when exposed to supernatant obtained from adherent cells of Ity(s) mouse strains. Thus, modulation of IFN-gamma production appears to be a function of the Ity(r) gene(s). This study documents for the first time that the Ity locus may play a role in controlling resistance to Salmonella infection by regulating IFN-gamma production by NK cells. PMID- 8473744 TI - Salmonella typhimurium induces IFN-gamma production in murine splenocytes. Role of natural killer cells and macrophages. AB - IFN-gamma is a cytokine known to play an important role in host defense against Salmonella typhimurium. The lymphoid cells required for in vitro production of IFN-gamma after S. typhimurium stimulation of mouse spleen cells was investigated. Spleen cells depleted of cells bearing NK1.1, asialo GM1, Thy 1.2, or CD5 resulted in a significant reduction in IFN-gamma production after stimulation with S. typhimurium. In contrast, Con A-induced IFN-gamma production was only slightly reduced after depletion of NK1.1- or asialo GM1-bearing cells. Spleen cells from SCID mice produced elevated levels of IFN-gamma after stimulation with S. typhimurium. IFN-gamma production by SCID spleen cells was dependent upon asialo GM1+ T cells, suggesting that NK cells were the cells producing IFN-gamma in response to S. typhimurium. Splenic adherent cells were required for optimal IFN-gamma production. However, direct contact between the adherent and nylon wool nonadherent (NWNA) cell populations was not essential. IFN-gamma production was observed when the adherent and NWNA cell populations were physically separated or when supernatant from S. typhimurium-stimulated adherent cells was added to NWNA cells. Optimal IFN-gamma production was dependent on the presence of TNF-alpha, inasmuch as addition of antibody to TNF alpha to spleen cell or NWNA cell cultures significantly reduced IFN-gamma production. However, addition of rTNF-alpha did not induce IFN-gamma production by NWNA cells. These findings document the existence of a T-independent mechanism for early IFN-gamma production in response to S. typhimurium, and show that TNF alpha is necessary but not sufficient for the production of IFN-gamma. PMID- 8473745 TI - Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor alpha. AB - Spleen cells from scid mice produce high levels of IFN-gamma when exposed to either live tachyzoites of Toxoplasma gondii or a soluble parasite extract. Small numbers of parasites are sufficient to stimulate this response, which is also induced by cell-free supernatants of cultured tachyzoites. The parasite molecules responsible for triggering IFN-gamma production are heat-labile but resistant to freezing and thawing. Depletion of NK cells or adherent cells from the splenocyte population abolishes the response. Moreover, cultured bone marrow-derived NK cells are stimulated by Toxoplasma to produce IFN-gamma, but only when supplemented with adherent peritoneal washout or thioglycollate-induced exudate cells. Supernatants of macrophages preincubated with T. gondii extract also induce IFN-gamma synthesis by cultured NK cells. Addition of neutralizing mAb against TNF-alpha abolishes the IFN-gamma response of scid spleen cells exposed to the parasite or of NK cells incubated with supernatants of adherent cells stimulated with T. gondii extract. Moreover, splenic adherent cells produce low levels of TNF-alpha in response to the parasite. Nevertheless, TNF-alpha alone is not sufficient to trigger IFN-gamma production from purified NK cell populations. These findings provide the first example of the stimulation of T-independent IFN gamma production by a protozoan. The ability of T. gondii to trigger this pathway may underlie its induction of strong IFN-gamma-dependent nonspecific and specific cell-mediated immunity. PMID- 8473746 TI - Regulation of expression of IL-1 receptor antagonist protein in human synovial and dermal fibroblasts. AB - The IL-1R antagonist protein (IRAP) is a competitive inhibitor of IL-1, which is predominantly synthesized by monocytes. We show that this molecule is also expressed in human synovial fibroblasts and dermal fibroblasts (CRL 1445). IRAP mRNA was regulated in a time- and dose-dependent manner by IL-1 alpha, TNF-alpha, LPS, and PMA. Maximal induction of IRAP mRNA was observed between 8 and 16 h after stimulation with IL-1 alpha (1 U/ml), TNF-alpha (10 U/ml), LPS (50 ng/ml), and PMA (10 ng/ml). Their relative efficacy was as follows: PMA > LPS > IL-1 alpha > TNF-alpha. Potentiation was observed when fibroblasts were treated with IL-1 alpha plus basic fibroblast growth factor and IL-1 alpha plus platelet derived growth factor-BB homodimer. Although LPS and PMA were the best inducers of IRAP mRNA, quantitation of the IRAP protein revealed that its synthesis and release were differentially regulated. Immunoprecipitation and SDS-PAGE of culture supernatant from LPS-treated cells and cell lysates of fibroblasts treated with LPS or PMA showed a single IRAP band with a molecular mass of approximately 22 kDa. Very little IRAP was detected in culture supernatants of cells treated with PMA. Quantitation of IRAP revealed that LPS induced the synthesis of secreted IRAP that was released, whereas the majority of the protein induced by PMA remained cell-associated. Reverse transcriptase-polymerase chain reaction amplification demonstrated that although LPS and PMA induced both transcripts, LPS preferentially induced secreted IRAP, whereas PMA differentially induced intracellular IRAP mRNA. Fibroblasts synthesize at least two different forms of IRAP depending on the inducing signal, and may regulate the inflammatory response by dampening the proinflammatory effects of IL-1 via a negative feedback mechanism with IRAP. The relative importance of fibroblast sIRAP vs intracellular IRAP in regulating the inflammatory response by the connective tissue remains to be determined. PMID- 8473747 TI - Anti-KCA-3, a monoclonal antibody reactive with a rat complement C3 receptor, distinguishes Kupffer cells from other macrophages. AB - A new mAb, designated anti-KCA-3, was developed against rat Kupffer cells. The reactivity of anti-KCA-3 was restricted to macrophages with preferential binding to Kupffer cells; only a few macrophages in the spleen, lymph nodes, lungs, and intestine stained with the antibody. A very small number of peritoneal resident and exudate macrophages reacted with the antibody and no reactivity was seen within the thymus, skin, heart, kidneys, brain, peripheral blood, and bone marrow. KCA-3 was expressed predominantly by the Kupffer cells in the periportal region rather than in the centrilobular region of the hepatic lobules. The cells in the portal tract did not stain with the antibody. The staining of the cytosmears and FACS analysis of the Kupffer cell fraction isolated from hepatic sinusoidal cells by centrifugal elutriation revealed that as many as 62% and 49% of the cells were stained with anti-KCA-3, respectively. Immunoelectron microscopic study of the liver indicated that expression of KCA-3 on Kupffer cells was limited to the plasma membrane facing the sinusoid rather than the space of Disse. Immunoprecipitation and SDS-PAGE analysis demonstrated KCA-3 to have a m.w. of approximately 50 kDa under both reducing and nonreducing conditions. After treatment of KCA-3 with N-glycanase, there was no significant change in the m.w., indicating KCA-3 was not highly glycosylated. C3b- and iC3b mediated rosette formation between Kupffer cells and sensitized SRBC was inhibited by the antibody, implying that KCA-3 functioned as a complement C3 receptor or complement receptor-associated molecule. Furthermore, KCA-3 was eluted from C3b-Sepharose but not HSA-Sepharose after incubation with Kupffer cell lysate, indicating that KCA-3 directly binds C3b. The cell distribution, ligand-binding specificity, and biochemical properties of the protein were found to be different from the complement C3 receptors previously described. Because OX42 (antibody reactive with the rat CR3 receptor) inhibited complement C3 mediated rosette formation with peritoneal resident macrophages but not with Kupffer cells, the findings suggest that C3-mediated binding to Kupffer cells and to peritoneal macrophages is mediated by two different receptors. We conclude that anti-KCA-3 recognizes a novel type of complement C3 receptor preferentially expressed on Kupffer cells. PMID- 8473748 TI - Picolinic acid, a catabolite of L-tryptophan, is a costimulus for the induction of reactive nitrogen intermediate production in murine macrophages. AB - In this study we investigated the effects of picolinic acid, a catabolite of L tryptophan, on the production of L-arginine-derived reactive nitrogen intermediates in the murine macrophage cell line ANA-1. ANA-1 macrophages did not produce nitrite (NO2-) constitutively, but accumulated detectable levels of NO2- on exposure to IFN-gamma. Picolinic acid, although ineffective by itself, augmented IFN-gamma-induced NO2- production. The activity of picolinic acid was evident at 1 mM and reached its maximum at 4 mM. Picolinic acid also augmented the IFN-gamma-dependent expression of TNF-alpha mRNA, but did not appreciably affect the secretion of the TNF-alpha protein. Neutralizing concentrations of anti-TNF mAb completely abrogated IFN-gamma- and IFN-gamma plus rTNF-alpha induced NO2- production in ANA-1 macrophages, but only decreased by approximately 50% the synergistic interaction between IFN-gamma and picolinic acid. Although IL 4 inhibited the expression of IFN-gamma plus picolinic acid-induced TNF-alpha mRNA and protein, it only partially suppressed picolinic acid-dependent NO2- production. Therefore, picolinic acid may affect NO2- production via both TNF alpha-dependent and TNF-alpha-independent pathways. Overall, this study suggests that amino acid catabolites may be important for the activation and the expression of effector functions by murine macrophages, and provides the first evidence of a possible connection between tryptophan and arginine metabolism. PMID- 8473749 TI - Complement factors H and I synthesized by B cell lines function to generate a growth factor activity from C3. AB - B lymphocytes and transformed B lymphoblastoid cell lines express CR2 (CD21, C3d/EBV-receptor) that is specific for C3 fragments generated by cleavage of C3b or spontaneously hydrolyzed native C3 (C3i) by the serum enzyme factor I and its cofactor, factor H. It had been shown previously that the Raji B cell line could be cultivated in serum-free medium supplemented with only transferrin and either OKB7 anti-CR2 mAb, C3d, or C3d-derived peptides containing the CR2 binding site. Because these agents appeared to function through ligation of CR2, it was unclear how native C3 could also serve as a growth factor, because C3 does not bind to CR2. It appeared possible that Raji cells might be able to use endogenous factors H and I to generate a CR2 ligand from C3, because previous studies had shown that Raji cells synthesized factor H and probably also synthesized factor I. PCR analysis was used to demonstrate factor I mRNA in Raji cells. Secretion of Raji cell factor I protein was confirmed by a sensitive mAb ELISA. Several B cell lines were examined for C3-dependent growth. Raji cells required both C3 (or OKB7) and transferrin for growth, whereas Wil-2 cells grew with transferrin alone and C3 enhanced the growth-promoting activity of transferrin. Two other B cell lines (Daudi and U698M), the T cell line 8402, and the U937 monocytoid cell line could not be sustained with transferrin plus C3. The C3-dependent growth of Raji cells was inhibited almost completely by either OX-23 anti-factor H or 052.11.3 anti-factor I mAb that also blocked the activity of serum-derived factor H or I, respectively. By contrast, there was no inhibition of growth by either OX-24 anti factor H or OX-21 anti-factor I mAb that did not block factors H and I activity. After the spontaneous hydrolysis of native C3 to C3i, it is hypothesized that Raji cells convert C3i to iC3i with endogenous factors H and I, and then this iC3i serves as a growth factor by binding to membrane CR2. PMID- 8473750 TI - Heterologous desensitization of the high affinity receptor for IgE (Fc epsilon R1) on RBL cells. AB - To study the properties of Fc epsilon RI desensitization induced by aggregation of that receptor, RBL cells were sensitized with a mixture of two different IgE mAb to create two different populations of IgE-receptor complexes. Cross-linking of one receptor population containing anti-dinitrophenyl (DNP) IgE with a bivalent Ag, 1-DNP-amino-12-biotinamidododecane)2-avidin ((DNP)2-avidin), results in desensitization of a subsequent response, both of the same receptor population (homologous desensitization) and of the second receptor population containing anti-5-dimethylaminonaphthalene-1-sulfonyl (dansyl) IgE (heterologous desensitization). The extent of heterologous desensitization is dependent on several parameters, including the concentration of both the first and the second Ag and the densities of the respective IgE populations. Heterologous desensitization of the Ca2+ response is more sensitive to the concentration of the second stimulus (dansyl-BSA) than heterologous desensitization of the degranulation response. AlF4-, which activates GTP-binding proteins, can effectively replace (DNP)2-avidin as the initial stimulant and desensitizing agent. Other agents that mobilize intracellular Ca2+ including thrombin and a Ca2+ ionophore are less effective at replacing (DNP)2-avidin. Because prestimulation with Ag does not desensitize subsequent responses to AlF4- or Ca2+ ionophore, it appears that signal transduction via Fc epsilon RI is impaired at an early step. Addition of monovalent DNP hapten within approximately 10 min after cross-linking by (DNP)2-avidin completely prevents the desensitization of the subsequent Ca2+ or degranulation response to dansyl-BSA. After longer times of incubation with DNP Ag, the DNP hapten becomes increasingly less effective at preventing the desensitization of the dansyl-BSA response, even though ongoing signal transduction by the DNP Ag is halted. These results suggest a form of cellular memory for the desensitized state. PMID- 8473751 TI - Diverse T cell receptor V beta gene usage in the central nervous system in experimental allergic encephalomyelitis. AB - The repertoire of TCR V beta genes transcribed and expressed within the central nervous system was determined in mice with experimental allergic encephalomyelitis. Disease was induced in (PL/J x SJL/)F1 mice by immunizing with myelin basic protein-acetylated peptide 1-11, and mice were sacrificed at intervals from day 3 postimmunization to 3 wk after recovery from disease. Transcription of V beta genes was determined by reverse transcriptase polymerase chain reaction on RNA extracted from spinal cord, and expression of the V beta gene products was detected by immunohistochemistry with mAb specific for various V beta proteins. Multiple V beta genes were found to be transcribed and expressed in the central nervous system starting 7 days after immunization, and continuing up to 3 wk after clinical recovery. Preferential utilization of a single TCR V beta gene was not detected in the central nervous system at any time in the course of disease. PMID- 8473752 TI - Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans. AB - TNF is effective in causing the regression of selected murine tumors when administered at high concentrations. Therapeutic levels in humans cannot be obtained systemically, however, because of dose-limiting toxicity. The development of immunotherapy with IL-2 and tumor-infiltrating lymphocytes (TIL), which can accumulate at tumor sites in some patients, and of efficient retroviral techniques for gene transfer into eukaryotic cells has allowed new therapeutic approaches using TNF. We have retrovirally transduced human TIL with the gene for TNF in an attempt to deliver high concentrations of TNF to the tumor site without dose-limiting systemic toxicity. Successful gene insertion was confirmed by Southern hybridization in 16 of 16 transduced and selected TIL cultures from 15 different patients, with an estimated 28 to 93% transduced cells within each culture. Transduced selected TIL cultures produced greater amounts of TNF, compared with nontransduced controls, in 11 of 16 cultures evaluated. However, overall production of TNF was > 30-fold lower, compared with a transduced and highly selected tumor cell line control (MEL-TNF). In addition, steady state levels of vector-derived transcript in nine of 10 transduced selected TIL cultures were < 14% of the amount seen in the MEL-TNF control line. In an attempt to increase TNF production, TIL were transduced with a mutated form of TNF containing the IFN-gamma signal peptide in place of the transmembranous region, to enhance secretion into the endoplasmic reticulum. By using this vector, TNF production increased by an average of fivefold. These studies demonstrate that TIL can be genetically modified to express and secrete a protein for use in targeted cancer therapy but that partial expression blockades exist that prevent maximal cytokine production by introduced genes in TIL. PMID- 8473753 TI - Superantigen can reactivate bacterial cell wall-induced arthritis. AB - Intravenous injection of toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus, can reactivate arthritis in a rat ankle joint that has been previously inflamed by injection of peptidoglycanpolysaccharide polymers isolated from the cell walls of group A streptococci. The severity and chronicity of this renewed arthritis is dose dependent and at higher doses (125 micrograms/kg) a prolonged joint inflammation with pannus formation and marginal erosion of cartilage and bone is induced after a single injection of TSST-1. Only modest synovial hyperplasia is induced in control ankle joints by systemic injection of TSST-1. Another superantigen, streptococcal pyrogenic exotoxin induces a much weaker, acute reactivation of arthritis that resolves by 2 days. Repeated injections of TSST-1 at 7-day intervals give the same undiminished pattern of joint response, but the joint swelling persists at a higher level with each succeeding injection. Cyclosporin A suppresses all phases of the recurrent arthritis, indicating that TSST-1 could be functioning through its property of a superantigen activating T lymphocytes. II-1 receptor antagonist and anti-TNF alpha neutralizing antibody, which reduce reactivation of arthritis by peptidoglycan-polysaccharide polymers, have no effect on reactivation by TSST-1. This experimental model provides a means to examine in vivo the possible role of superantigens in rheumatoid arthritis and related diseases, and to analyze the cellular and molecular pathways induced by this family of microbial products. PMID- 8473754 TI - lpr T cells are necessary for autoantibody production in lpr mice. AB - Mice homozygous for the gene Ipr develop a spectrum of autoantibodies closely resembling that of human SLE. Previous work has shown that the lpr defect must be expressed in the T cells that hyperproliferate and in the B cells that produce autoantibodies. Although autoantibody production in lpr mice requires T cells, it is not known whether these need to be lpr T cells. To ask whether normal (+/+) T cells can help lpr B cells produce autoantibodies, we have constructed chimeras containing mixtures of lpr-derived and normal-derived lymphoid cells, and have selectively eliminated the lpr-derived T cells by in vivo treatment with monoclonal anti-Thy-1 of the appropriate allotype. A mixture of T cell-depleted bone marrow from congenic strains of normal and lpr mice differentially marked by Ig H chain allotype and Thy-1 alleles was transferred into lethally irradiated lpr mice. The mice received weekly injections of either anti-Thy-1.2 to deplete specifically lpr T cells or an isotype-matched irrelevant control mAb. Absence of lpr-derived T cells in the experimental group was documented by immunofluorescence. In mice treated with control antibody, autoantibodies of Ipr origin were present in high titers, as determined by allotype-specific ELISA. In contrast, mice depleted of lpr-derived T cells had greatly reduced titers of antichromatin and rheumatoid factor. These mice also had increased levels of serum total IgM and IgG2a of +/+ origin. Parallel experiments were performed using a combination of two lpr marrow sources, also differentially marked by Ig H chain allotype and Thy-1 expression. Mice depleted of Thy-1.2-bearing T cells produced autoantibodies of both allotypes due to the presence of Thy-1.1-bearing T cells of Ipr origin. These data indicate that autoantibody production in lpr mice requires expression of the lpr gene in those T cells that provide help. PMID- 8473755 TI - Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. AB - To investigate the role of the class I MHC molecule HLA-B27 in the spondyloarthropathies, we produced rats transgenic for HLA-B27 and human beta 2 microglobulin. Of five lines bearing > 1 copy of each transgene and showing hemizygous expression of both transgenes, two (lines 21-4H and 33-3) developed spontaneous inflammatory disease that closely resembled B27-associated human disease. Two lines, 21-4L and 25-6, remained healthy even when homozygous for the transgene locus, whereas the 21-3 line, bearing the third highest transgene copy number, developed disease similar to that of the 21-4H and 33-3 lines only when homozygous for the transgene locus. The disease-prone lines showed higher expression of B27--thymic mRNA in utero, splenic mRNA by 5 days of age, and splenic cell surface protein by the time of disease onset--than the disease resistant lines. Disease susceptibility thus appeared to correlate with gene copy number and the quantity of B27 in lymphoid cells. The increase in the amount of B27 protein did not appear to be simply a consequence of the inflammatory disease because 1) there was no similar change in endogenous RT1 class I expression; 2) no alteration of B27 expression occurred in 21-4H rats with adjuvant-induced arthritis; 3) in rats with inflammatory disease transgenic for HLA-A2 and the 21 4H transgene locus, A2 expression was the same as in healthy rats transgenic for A2 but not B27; and 4) the transgenes in disease-prone and disease-resistant lines were equally susceptible to induction by IFN-gamma. Immunocytochemistry of the distal colon, an early site of inflammation, showed that the B27 Ag is expressed at high levels in cells of the lamina propria, but not at all in colonic epithelial cells. Taken together, the data suggest that the B27 transgene is expressed in a copy number dependent, position-independent manner in lymphoid tissue and that disease results from the expression of B27 above a critical threshold level. PMID- 8473756 TI - Increased IL-6 production and IL-6-mediated Ig secretion in murine host-vs-graft disease. AB - BALB/c mice neonatally injected with semiallogenic (A/J x BALB/c)F1 splenocytes develop a host-vs-graft (HVG) reaction between host T cells and donor B cells, resulting in hypergammaglobulinemia, splenomegaly, and increased serum levels of various autoantibodies. This syndrome is associated with a polyclonal activation of the donor-derived B cells. High serum levels of IL-6 were found in 4-wk-old mice undergoing HVG disease (mean +/- SEM, 132 +/- 93 as compared with 12 +/- 2 in control mice, p < 0.05). Also supernatants of spleen cell cultures from HVG mice contained increased levels of IL-6. In situ hybridization and cell depletion experiments demonstrated that host macrophages were responsible for this pathologic IL-6 secretion. The spontaneous in vitro production of autoreactive antibodies by donor B cells from HVG mice was further enhanced by adding human rIL-6, whereas addition of human rIL-1 beta, human rIL-2, murine rIL-4, murine rIL-5, or combinations of these cytokines had no effect. Finally, addition of blocking anti-IL-6 and anti-IL-6 receptor mAb markedly reduced hyper IgG1 production in cultures of spleen cells from HVG mice. These data suggest that an increased production of IL-6 by persistently stimulated host macrophages is involved in the activation of donor B cells leading to HVG disease. PMID- 8473757 TI - Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure. AB - Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis. PMID- 8473758 TI - Fluconazole resistance in Candida in patients with AIDS--a therapeutic approach. PMID- 8473759 TI - Candidaemia: risk factors in patients with cystic fibrosis who have totally implantable venous access systems. AB - Patients with cystic fibrosis who have totally implantable venous access devices often have other consequences of their multi-system disease which predispose them to catheter-associated systemic infection. We describe four episodes of fungaemia in three patients. Each case presented with persistent fever during an acute respiratory exacerbation. The four episodes were successfully treated, but removal of the venous access device was necessary in each case. Identified risk factors for systemic fungal injection were: combinations of a severe background respiratory deficiency; an acute respiratory exacerbation; malnutrition; repeated and frequent broad spectrum antibiotic therapy; parenteral nutrition; and diabetes mellitus. Unexplained fever in high risk patients with cystic fibrosis who have indwelling venous access systems should be treated empirically with antifungal agents while awaiting blood culture results. If fungaemia is confirmed the venous access device must be removed. Daily prophylactic fluconazole may prevent recurrences. PMID- 8473760 TI - Treatment of Candida albicans fungaemia with fluconazole. AB - Sixty-five patients with Candida albicans fungaemia, admitted to intensive care units, were treated intravenously with fluconazole. All patients had at least one blood culture which was positive for C. albicans. The first group of 34 consecutive patients received fluconazole at a dose of 5 mg/kg bodyweight/day and the subsequent 31 patients received 10 mg/kg/day. Thirty patients in each group were evaluated. The clinical response rate was 60% in the 5 mg/kg once daily group and 83% in the group which received 10 mg/kg/day. Eradication of C. albicans from the blood was achieved in all but two patients in the 5 mg/kg group and in all patients in the 10 mg/kg group. As regards other sites of infection, eradication was achieved in only nine of 25 cases from the 5 mg/kg group and in 11 of 23 cases from the 10 mg/kg group. Death related to fungal infection occurred in eight patients receiving 5 mg/kg/day and in one patient receiving 10 mg/kg/day. Fluconazole was reasonably well tolerated. Raised concentrations of liver enzymes were observed in 14 patients. Other adverse effects were fatigue, nausea, gastric pain, sleepiness and epileptic seizure. In conclusion, fluconazole at a dose of 10 mg/kg/day would seem to be an effective and safe drug for the management of C. albicans fungaemia. PMID- 8473761 TI - Application of the polymerase chain reaction to the diagnosis of human toxoplasmosis. AB - Toxoplasmosis may cause significant damage to the developing fetus and is a life threatening opportunistic infection in immunocompromised persons. Serological investigation is unreliable, while isolation of the parasite is time consuming and may lack sensitivity. We have developed a system for detecting Toxoplasma gondii based on the amplification of the P30 gene using sequential rounds of PCR and nested primers. The clinical value of this technique was assessed by the investigation of a range of tissues taken from pregnant women, fetuses, neonates, AIDS patients and organ graft recipients. The PCR assay produced more positive reactions than isolation of the parasite by means of cell culture or animal inoculation. Extended autoradiography was found to be more sensitive than stained agarose gels for detecting the PCR product. Systematic contamination of PCR reactions was avoided but it was not possible to exclude sporadic contamination in certain cases. Detection of specific DNA is of clinical value in the investigation of the pregnant woman in order to assess the risk of transplacental passage of infection and in the fetus and neonate to identify congenital toxoplasmosis. Even so, PCR findings must be interpreted with caution because of the risk of a sample being contaminated. PCR may be the investigation of choice when brain biopsy is performed on a patient with AIDS and when toxoplasmosis associated with bone marrow transplantation is suspected. PMID- 8473762 TI - Septic shock in critically ill patients: aetiology, management and outcome. AB - Over a period of 28 months, 45 episodes of septic shock from 83 episodes of bacteraemia were studied prospectively to evaluate their clinical profile, management and outcome. Thirty-six patients were studied, the overall incidence of septic shock being 54.2%. Gram-negative organisms accounted for 23 (51.1%) of such episodes, Gram-positive 17 (37.8%), and three episodes were polymicrobial (6.7%). The organisms isolated most frequently were Staphylococcus epidermidis (17.8%), Pseudomonas aeruginosa (13.3%), Escherichia coli and Klebsiella sp. (each 11.1%). Coagulation abnormalities were detected in 32 episodes (78%) and disseminated intravascular coagulation (DIC) occurred in 11 of these with high mortality. The most common underlying conditions were respiratory, hepatic and renal failures. The majority of these patients received crystalloids, colloids, vasopressor drugs and blood. Swan-Ganz catheters (SGC) were inserted on eight occasions, the majority of times indicating a hyperdynamic circulatory response. The overall mortality was 40%, despite aggressive management and intensive care. The most important factor in reducing mortality is early detection of bacteraemia and prompt management of these patients. PMID- 8473763 TI - Schistosomiasis in Leicester. AB - Twenty-two cases of schistosomiasis were diagnosed in the Infectious Diseases Unit in Leicester during a 5-year period. There were 11 cases of Schistosoma haematobium infection and three of S. mansoni infection. The schistosoma type in the remaining eight cases was uncertain. Fourteen asymptomatic family members of patients with proven schistosomiasis were screened and 6 (43%) had evidence of schistosomal infection. Seventeen (77%) of the patients were thought to have been infected in Malawi and all but one of these had swum in Lake Malawi. The study highlights the large proportion of cases who acquired infection in Malawi and emphasises the importance of family screening. PMID- 8473764 TI - Fatal disseminated adenovirus type 2 infection following bone marrow transplantation for Hurler's syndrome: a primary infection. AB - A 5-month-old girl given an allogeneic bone marrow transplant for Hurler's syndrome succumbed to fatal pneumonia 5 weeks after the transplant. Adenovirus type 2 was isolated from her urine before she died. Immunoperoxidase and electron microscopical studies of liver and lungs post mortem confirmed a disseminated adenovirus infection. The serological findings and the patient's young age suggested that the infection was a primary one. The importance of considering exogenous sources of adenovirus infection in bone marrow transplant recipients is discussed. PMID- 8473765 TI - Cardiac dysfunction in paediatric HIV infection. AB - A child under long term surveillance for vertically acquired HIV-I infection developed respiratory symptoms. Dilated cardiomyopathy was diagnosed. Clinical and echocardiographic assessment of six other children with symptomatic HIV disease showed no evidence of cardiac dysfunction. The exact prevalence of this complication in paediatric HIV infection is unknown, but the potential diagnostic difficulties are highlighted. PMID- 8473766 TI - Highly virulent Streptococcus pyogenes rheumatic pancarditis and fatal septicaemia with septic shock. PMID- 8473767 TI - Retained Hickman catheter cuff as a source of infection. AB - Two cases of Pseudomonas aeruginosa infection complicating retained subcutaneous Hickman catheter cuffs are described. Foreign body-associated Pseudomonas infection is unlikely to respond to treatment with antibiotics alone. We therefore recommend that the cuff is removed at the same time as the Hickman catheter is pulled out so as to prevent future infection. PMID- 8473768 TI - Disseminated blastomycosis masquerading as tuberculosis. AB - Two patients were mistakenly treated for several months for tuberculosis. Both had lung and vertebral involvement and one patient had superficial skin lesions as well. Blastomycosis was eventually confirmed by fungal culture, but only after both patients had deteriorated markedly; one died soon after treatment with amphotericin B was started. In Africa, blastomycosis is a relatively rare condition which can mimic tuberculosis; it is one of several infections which should be borne in mind when dealing with apparently non-responsive tuberculosis. PMID- 8473769 TI - Citrobacter diversus ventriculitis and brain abscesses in an adult. AB - A case of Citrobacter diversus brain abscesses following urinary infection in an adult is described. The patient was treated with surgical drainage, netilmicin and cefotaxime. Citrobacter species CNS infection is discussed. PMID- 8473770 TI - Primary amoebic meningo-encephalitis in southern Africa. AB - A fatal childhood case of confirmed primary amoebic meningo-encephalitis due to Naegleria fowleri is reported. This appears to be the first such case identified in southern Africa. The diagnosis and management of this unusual and lethal infection is discussed and attention is drawn to the possible danger of swimming in contaminated warm water. PMID- 8473771 TI - Haemophilus influenzae type b disease in north-west England. AB - A study was made in the north-west of England during 1989 in order to ascertain the incidence of serious Haemophilus influenzae infection, its short-term morbidity and certain characteristics of treatment. The incidence of culture proven infection was 28 per 100,000 children under 5 years of age. Case fatality was 3%, one of the deaths being in a 6-year-old child. Some of the information obtained will help to assess the cost-effectiveness of the new vaccine to be administered to children in the U.K. The mean length of stay in hospital for all cases was 10 days. Of a total of 87 patients, 20 (23%) were admitted to an intensive therapy unit while five were transferred from a district general hospital to a regional paediatric unit. The estimated average cost per episode of acute care was 2700 pounds. Antibiotic regimens varied considerably. PMID- 8473772 TI - Clenched fist actinomycosis in a penicillin-allergic female. PMID- 8473773 TI - Mycobacterium malmoense infection in an immunocompromised patient. PMID- 8473774 TI - Recurrent Mycobacterium bovis infection following a ferret bite. PMID- 8473775 TI - Rapid diagnosis of tuberculous meningitis. PMID- 8473776 TI - Enterovirulent Escherichia coli can cause bacteraemia in immunocompromised patients. PMID- 8473777 TI - Detection of verotoxin-producing strains of Escherichia coli. PMID- 8473778 TI - Serum albumin and other parameters in HIV infected intravenous drug users. PMID- 8473779 TI - [Evaluation of results following thymectomy in myasthenia gravis]. AB - Sixty-nine patients with generalized myasthenia gravis underwent thymectomy consecutively between 1980 and 1991 and were evaluated 1 month to 120 months after operation. Extended thymectomy was performed in 43 patients and other procedures in 26. The effect of thymectomy were as follows: 14.5% of the patients achieved complete remission (no symptoms, no medication), 73.9% showed improvement; in total 88.4% had palliation. The long-term changes of the remission rate at one and five years after operation were 11.5% and 19.2%, and showed a delayed remission. The long-term changes of the improvement and palliation rate were 55.7% and 67.2% at one year, 69.2% and 88.5% at five years after operation. There was significant difference in remission rate according to age at the time of operation and age of onset, but the response did not depend on sex, presence or absence of thymoma, preoperative duration of illness, Osserman's type and operative procedure. PMID- 8473780 TI - [Mechanisms of organ failure following cardiopulmonary bypass--preventive effects of Ca2+ blocker (nicardipine)]. AB - The causes of organ failure following cardiopulmonary bypass (CPB) were multi factorial. Damage was initiated by elastase which was released from activated granulocytes under conditions of significant reduction in the protease inhibitor level (p < 0.01). The increase in endothelin excretion observed during and after the CPB induced a further vasoconstrictive response in the microvasculature and accelerated ischemic cellular damage. Upon completion of the CPB, the elevation of the lysosomal enzyme beta-glucuronidase was influenced by the elastase and endothelin concentrations (r = 0.8 and r = 0.67 respectively). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D glucosaminidase and gamma-glutamyltranspeptidase), was affected by endothelin (r = 0.61, 0.75) and elastase concentrations (r = 0.74, 0.75) respectively. In the group treated with nicardipine during the CPB, an increase in beta-glucuronidase was significantly low (p < 0.01) and renal tubular damage was significantly reduced. Moreover, lesser elevation of the elastase level on arrival in the ICU was evidenced (p < 0.05). Thus we concluded that nicardipine inhibited the release of elastase from the activated neutrophils and prevented the vasoconstriction caused by the endothelin secretion. PMID- 8473781 TI - [Effectiveness of erythropoietin for cardiovascular surgery to prevent homologous blood transfusions]. AB - Erythropoietin (EPO) was used preoperatively in 109 cardiovascular surgery cases to prevent homologous blood transfusions. Operative procedures in all these cases were coronary artery bypass grafting in 80 cases, valve replacement in 14, and a few cases of aortic vascular replacement or others, aging about average 62 years and weighing about average 54 kg. EPO was administered concomitantly with oral iron sulfate in the following three different manners; 100 units per body weight daily intravenously, 300 U./B.W. twice in a week intravenously, and 600 U./B.W. once in a week subcutaneously. Autologous blood donations were also performed as long as the blood hemoglobin levels were over 12 (g/dl) and repeated until the date of operation, and these blood deposits were returned to each patient at the time of operation. The blood hemoglobin level had increased on average from 12.6 (+/- 1.5 SD) to 13.6 (+/- 1.2 SD) after 23 days (+/- 13 SD) administration of EPO, while autologous blood deposit of 536 ml (+/- 353 SD) was obtained. Homologous blood transfusions were unnecessary in 89% of all cases, especially good in 96.7% of the group with over 12 of hemoglobin level before EPO administration. However, it remained within 79.6% of those with lesser to 12, so there was still room for improvement in this anemic group. No adverse effects were recognized in all cases. It was concluded that preoperative use of EPO is efficient to promote autologous blood donation, and its application will be expanded to anemic cases. EPO could offer an excellent means of preventing homologous blood transfusion. Further study concerning the appropriate application of erythropoietin seems to be required. PMID- 8473782 TI - [Biventricular repair with a modified Glenn shunt for the hypoplastic right ventricle]. AB - Between 1982 and 1990, 14 patients with small right ventricle underwent biventricular repair with a modified Glenn shunt. The patients consisted of 8 cases of pulmonary atresia and intact ventricular septum, 2 with pulmonary stenosis and intact ventricular septum, 3 with tetralogy of Fallot, 1 with pulmonary atresia and straddling tricuspid valve. Nine patients had one or more prior preliminary palliative procedures. Repairs consisted of a modified Glenn shunt and closure of the intracardiac and extracardiac shunt, with right ventricular outflow reconstruction in 13, and pulmonary valvotomy in 1. In nine patients superior vena cava was not ligated. There was one operative death (7%). Preoperative RVEDV ranged from 19 to 70% of normal with a mean of 36.1% of normal. Preoperative pulmonary resistance ranged from 1.6 to 5.3 unit with a mean of 2.8 unit. Preoperative PA index ranged from 102 to 444 mm2/m2 with a mean of 234.3 mm2/m2. No patients died later. Follow-up 2 to 9 year after operation showed that 9 patients were in the New York Heart Association class I and 4 were in class II. Our experience shows that this procedure can be safely done for patients, who have hypoplastic right ventricle smaller than 40% of normal and are not candidate for Fontan procedure because of high pulmonary vascular resistance and inadequate size of pulmonary artery. In this procedure a modified Glenn shunt without ligation of SVC may effectively reduce the volume overload on the right ventricle. PMID- 8473783 TI - [Surgical repair of total anomalous pulmonary venous drainage--four adult cases of successful operation]. AB - We have experienced four adult cases of total anomalous pulmonary venous drainage (TAPVD). They were three females and one male, age between 18-51 with a mean of 33.8. In Darling's classification, they constituted of three cases of type Ia and one type IV. Cardiac catheterization revealed 1.71-5.93 with a mean of 3.92 in Qp/Qs and 0.34-0.49 with a mean of 0.38 in Pp/Ps. The pulmonary to systemic resistance ratio (Rp/Rs) was then calculated as 0.02-0.15 with a mean of 0.09. All cases showed short route type of drainage vein in pulmonary arteriography. None of them had stenosis or obstruction in the drainage veins. The operation was composed of anastomosis between the left atrium and the common pulmonary vein, closure of the atrial septal defect (ASD), and ligation of the drainage vein. Gersony-Malm's method was adopted in two cases and the posterior approach in two cases in anastomoses between the left atrium and the common pulmonary vein. Intraatrial approach combined with posterior approach was tried in a case with small left atrium. The mean size of ASD was 43 mm (35-55 mm) in diameter. Patch closure was performed in three cases. Important factors in survival for adult TAPVD are large ASD and short route type drainage vein without stenosis. All of four cases had good results. The operation method is variable and an easier approach must be adopted. PMID- 8473784 TI - [Cerebral renal and hepatic tissue blood flow during retrograde inferior vena caval perfusion--an experimental study in dogs]. AB - Cerebral tissue blood flow (CBF), renal tissue blood flow (RBF), hepatic tissue blood flow (HBF), and oxygen metabolism have been measured in 8 mongrel dogs which underwent hypothermic (20 degrees C) retrograde perfusion via the inferior vena cava (IVC). IVC perfusion was performed with aortic drainage and cross clamping of superior vena cava (SVC) at IVC pressures of 20 or 30 mmHg. CBF, RBF, and HBF at 30 mmHg of IVC pressure were 10.4 +/- 6.8, 11.4 +/- 5.5, and 19.2 +/- 11.3 mL/min/100 g. These values were 33%, 47%, and 64% of those observed with a cardiopulmonary bypass and flow rate of 1000 mL/min, and 77%, 112%, and 168% of those observed with retrograde cerebral perfusion via the both internal maxillary veins at 25 mmHg of SVC pressure. Oxygen consumption at this time was 3.78 +/- 1.77 mL/min. CBF, RBF, HBF, and oxygen consumption at 20 mmHg of IVC pressure were 7.7 +/- 4.8, 7.5 +/- 4.7, and 9.9 +/- 4.7 mL/min/100 g and 2.02 +/- 0.72 mL/min, respectively. As IVC pressure increased, CBF, RBF, HBF, and oxygen consumption increased. However, high IVC pressure by the retrograde perfusion was associated with high portal venous pressure, which would cause ascites. IVC perfusion can supply some amount of blood flow to the liver and kidney. It may therefore be advantageous to maintain proper IVC pressure to protect the abdominal organs during systemic arterial circulatory arrest under deep hypothermia. PMID- 8473785 TI - [Effect of intravenous recombinant human superoxide dismutase on reducing reperfusion injury]. AB - This study was performed to evaluate effects of recombinant human superoxide dismutase (r-hSOD) administered intravenously just prior to reperfusion on reduction of reperfusion injury by using regional left ventricular function recovery in quantitatively controlled reperfusion model. Mongrel dogs underwent 2 hours of left anterior coronary artery clamping followed by 30 minutes of partial reperfusion (25% of control flow) and 30 minutes of full reperfusion (full opening of occluder). Regional left ventricular functions: % segmental shortening (%SS), % active shortening (%AS) = systolic shortening/total shortening, were evaluated during reperfusion. Dogs were divided into 2 groups, Control group and SOD group: r-hSOD was administered 100,000 Unit/kg in bolus intravenously before reperfusion. Measured left ventricular segments were classified by temperature drop in thermography into the central (> or = 2 degrees C) and the marginal (< 2 degrees C) ischemic zones. In the central ischemic zone, the values of %SS before left anterior descending coronary artery clamping were 11% and 12% in Control and SOD groups, respectively. Just after occlusion of coronary artery, %SS dropped down to the range of -5% to -7% and kept the same level during ischemia. After partial reperfusion, there was no significant difference of %SS between Control and SOD groups, however, after full reperfusion, %SS of SOD group showed better improvement than that of Control group (p < 0.05). As for %AS in the central ischemic zones, the same tendency was present. In the marginal ischemic zone, the values of %SS went down when left anterior descending coronary artery was occluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473786 TI - [Surgical treatment of double orifice mitral valve in atrioventricular septal defect]. AB - Ten patients with double orifice mitral valve and atrioventricular septal defect (AVSD) were examined. There were four cases with incomplete type, three with intermediate type and three with complete type AVSD. All patients with incomplete type AVSD were doing well after the mitral cleft repair, Leaving the accessory orifice untouched. Various valve repair procedures and prosthetic valve replacement were performed in the patients with intermediate and complete types of AVSD with left-sided atrioventricular valve regurgitation. There were three operative deaths, which included one patient with the intermediate type and two with the complete type. All of them were one-month old babies and were operated on emergency. Their general operative findings were hypoplasia of the common atrioventricular valve leaflets, abnormal attachment of the chorda tendineae and papillary muscle dysplasia. These findings increased the difficulty of the valve plasty to control mitral regurgitation. PMID- 8473787 TI - [Composite valve graft replacement for aortic root aneurysm or dissection]. AB - Fifty four patients who had aneurysms (n = 35) or dissections (n = 19) associated with aortic regurgitation underwent the replacement of the ascending aorta and aortic valve by composite valve graft during 15-year period between September 1976 and December 1991. Of these, 49 (90.7%) patients had an annuloaortic ectasia and 26 (48.1%) had the Marfan syndrome. The methods of coronary artery reattachment to the graft were as follows: direct reattachment (original Bentall's technique) in 45 patients, aortic button technique (Carrel's patch technique) in 6, Cabrol's technique in 2 and Piehler's technique in 1 patients. Seven patients with a DeBakey type I dissection had concomitant replacement of the aortic arch with an aid of selective cerebral perfusion. The overall hospital mortality rate was 12.9%, and it has significantly decreased to 6.7% since we adopted a cold cardioplegia, preclotting the graft with albumin autoclave technique and coronary artery reattachment using conventional over-and-over and interrupted mattress sutures with pledgets during the last 10-years. The mean duration of follow-up period was 58.6 months. The actuarial survival rate at 10 years for all patients was 76.4%; for those with dissection, 78.4%; and for patients with Marfan syndrome, 70.4%. Reoperation for the prosthesis-related complications was necessary in only one patient, although operations on the remainder of aorta were required in 5 patients. Actuarial freedom from these operations at 10 years was 74.1%, but it was 69.3% for the subgroup with Marfan syndrome. The present data indicates that composite valve graft technique is an useful method for patients with aortic root aneurysms or dissections. PMID- 8473788 TI - [The significance of body weight measurement of esophageal cancer patients in intra- and postoperative fluid administration]. AB - We tried to clarify the intra- and postoperative pathological state in resected thoracic esophageal cancer patients and analyze the particularity of fluid administration by measuring body weight at certain time serially. We studied 26 resected thoracic esophageal cancer patients between September, 1989 and January, 1991 who underwent an operation through right thoracotomy prior to laparotomy at the same time, and all cases were under general anesthesia combined with epidural anesthesia. We measured body weight preoperatively, just after operation, on the first, second and third postoperative days by means of LIFTER (Ted Hoyer & Co. Inc), and also calculated water balance and measured pressures and cardiac output by Swan-Ganz catheter in 19 cases. As a result, change in body weight was remarkable in resected thoracic esophageal cancer patients intra- and postoperatively. The peak of weight gain was noticed and they gained about 3 kilograms in weight on the 1st postoperative day, while in circulation hypovolemia was found on the data by means of Swan-Ganz catheter. There was a high correlation between rate of change in weight (kg/hr) and water balance (ml/kg/hr) (r = 0.91). We calculated insensible loss by the difference between water balance and body weight. It was about 1.73 intraoperatively, 0 postoperatively, 0.35-0.5 ml/kg/hr on from the 1st through the 3rd postoperative day. It is concluded that body weight measurement is a very easy, precise and useful bedside technique in the intra- and postoperative fluid administration of esophageal cancer patients, because it is very important not only to understand the circulation volume but also to know the interstitial fluid change. PMID- 8473789 TI - [Participation of platelet activating factor in the pulmonary injury during cardiopulmonary bypass]. AB - Activations of leukocytes and platelets have been considered to be one of the major harmful factors related to Adult Respiratory Distress Syndrome (ARDS). As a hypothesis of the present study, similar events may exaggerate the post perfusion lung syndrome following the cardiopulmonary bypass (BPB). Since platelet activating factor (PAF) is a strong activator of leukocytes and platelets, we measured the kinetics of PAF level, number of leukocytes and platelets in 20 anesthetized dogs. beta-TG and PF4 were also measured in patients with organic heart disease before and after CPB. We also studied the preventive effects of PAF antagonist (CV-3988) on the postperfusion lung injury in dogs. The PAF activities increased twice 5 minutes after the beginning of CPB, then it was progressively increased to a level 4.5 times at the end of CPB. Circulating numbers of leukocytes and platelets depleted sharply after the CPB, and then decreased gradually. Such depletion was not modified by PAF antagonist, CV-3988. Accumulation of leukocytes at the pulmonary circulation, and the microscopic evidence of leukocyte sequestration in pulmonary capillary beds were noted in cases without PAF antagonist. Rapid increases of beta-TG and PF45 minutes after the beginning of CPB also showed that activation of platelets occurs immediately. Adhesion of activated leukocytes or platelets to the pulmonary capillary bed in dog cases may suggest the ensuring damage to the vascular beds by releasing free radicals, lysosomal enzymes, or other chemical mediators. Restriction of inflow rate of activated leukocytes to the lung or the heart before aortic clamping may attenuate harmful effects of leukocytes on the respiratory function related to the CPB. PMID- 8473790 TI - [A clinical trial of recombinant human superoxide dismutase for myocardial protection]. AB - This study explored the effect of recombinant human superoxide dismutase (rh-SOD) for the prevention of reperfusion injury and the myocardial protection in open heart surgery. Fifty one patients undergoing cardiac valve replacements were divided into the following four groups; group I (n = 14), 50 ml of saline was administered through the aortic root into the coronary artery a few minutes prior to reperfusion; group II (n = 14), rh-SOD (10000 U/kg) was administered as the same manner as the group I; group III (n = 13), rh-SOD (10000 U/kg) was administered into the cardiopulmonary circuit a few minutes prior to reperfusion; group IV (n = 10), rh-SOD (3000 U/kg) was administered as the same manner as the group III. They received continuous perfusion of cold blood and GIK solution every 30 minutes. Arterial blood samplings for Creatine phosphokinase MBisozyme (CPK-MB), alpha-hydroxy lactic acid dehydrogenase (HBDH), thiobarbituric acid reactive substance (TBA) were measured up to 24 hours after the reperfusion. CPK MB values at 12 and 24 hours after reperfusion, and HBDH value at 12 hours after the reperfusion in group II were significantly lower than those in group I. CPK MB and HBDH levels in group III were lower than group I without statistically significant differences. TBA levels in group II at 9 and 12 hours after the reperfusion were lower than these in group I. TBA levels were not statistically different in group I, III and IV. These results suggest that administration of rh SOD at the time of reperfusion may be required to prevent reperfusion injury in open heart surgery. PMID- 8473791 TI - [Surgical treatment of aortic valve regurgitation associated with Behcet's disease]. AB - We experienced a patient of aortic valve regurgitation associated with Behcet's disease. The patient underwent aortic valve replacement. There are 15 cases of valvular heart disease associated with Behcet's disease including this reported case. Patients often have perivalvular leakage after valve replacement because not only the aortic but also the surrounding aortic walls become inflamed from the effects of Behcet's disease. We treated our patient to prevent complication. The aortic valve was fixed from the outside of a 2/3 round aortic wall using a teflon strip. The operation was performed when the inflammatory signs and findings subsided, and an adrenal steroid was used after the operation. Satisfactory results were obtained, but since Behcet's disease is systemic progressive and chronic disease, strict observation of the patients and systemic controls of inflammation should be recommended continuously. PMID- 8473792 TI - [A case of T-cell type malignant lymphoma of the lung]. AB - A case of T-cell type malignant lymphoma of the lung was reported. A 69-year-old woman was referred to our institute because of an abnormal shadow on the chest roentgenogram. She was symptom-free, and physical examination showed no abnormalities. Her laboratory tests were within normal limits. The chest roentgenogram showed a well-defined, nodular density in the left lower lung field without air bronchogram. She underwent a left lower lobectomy and a mediastinal lymphnodes dissection. This disclosed an elastic hard nodule, 2 cm in diameter, without pleural invasion. Pathologically the tumor was diagnosed as malignant lymphoma of T-cell type without regional lymphnode involvement. She is doing well without any sings of recurrence for one year after the operation. PMID- 8473793 TI - [A case report of a chronic traumatic thoracic aneurysm]. AB - A successful experience of a case with chronic traumatic thoracic aneurysm is reported. A 51-year-old male patient had a history of a blunt chest trauma in a traffic accident one and a half year ago. He developed gradual hoarseness because of the recurrence nerve paralysis. Computed tomography and angiography revealed a saccular aneurysm at thoracic descending aorta. It was treated with direct closure of the tear under partial clamp of the aorta. His postoperative course was excellent. He is doing well two years after operation. PMID- 8473794 TI - [A case of mitral regurgitation caused by total rupture of the posterior papillary muscle after acute myocardial infarction]. AB - We observed a case of severe mitral regurgitation caused by total rupture of the posterior papillary muscle 13 days after acute myocardial infarction. The patient was a 76-year-old man who suddenly felt anterior chest pain. He was admitted to another hospital with the diagnosis of acute myocardial infarction. Electrocardiogram suggested a posterior infarction. He did well during the first 12 days of hospitalization, but at noon on the 13th day he developed anterior chest pain and dyspnea. Echocardiography demonstrated rupture of the posterior papillary muscle. He was subsequently transferred to our hospital with acute heart failure. He was initially treated with an intra-aortic balloon pump. Cardiac catheterization demonstrated 99% stenosis of segment 2 of the right coronary artery and mitral regurgitation, Sellers' stage IV. Intraoperative findings included total rupture of the posterior papillary muscle. Mitral valve replacement was performed using a Carbomedics prosthetic valve. The patient was discharged 53 days after surgery without heart failure or angina pectoris. This case represents the 6th successful operation of total papillary muscle rupture in Japan. PMID- 8473795 TI - [A case of the successful treatment of pulmonary artery pseudoaneurysm after PA banding]. AB - Pulmonary artery pseudoaneurysm after PA banding is a rare complication and its mortality is very high. The authors successfully operated on this sort of lesion. To our knowledge, this is the first successful case in Japanese literature. The second of twins was found to be suffering asplenia, dextro cardia, TAPVC, atrioventricular septal defect, corrected TGA and PDA. On the 19th day of life, increasingly pulmonary congestion forced us to operate. We performed PDA ligation, correction of TAPVC, together with extrathoracically adjustable PA banding. 5 months following this operation, spike fever and swelling of anterior thorax were noted. PA angiography was performed, and it showed that the pulmonary artery had been cut through by the band and a pseudoaneurysm had developed. The PA banding was removed and an end-to-end anastomosis of the PA was performed using cardiopulmonary bypass and deep hypothermia with surface cooling. The diameter of the PA anastomosis was designed to be one half that of her aorta. Staphylococcus aureus was cultured from the specimen of the PA band. It was thought to have contributed to the development of this aneurysm. The post operative course was uneventful. PMID- 8473796 TI - [Primary chondrosarcoma of the pulmonary artery]. AB - A 69-year-old woman who had progressive dyspnea, edema and oliguria was diagnosed as primary sarcoma arising in the pulmonary trunk by preoperative examination. She received thoracotomy and total resection of the tumor in the pulmonary trunk utilizing cardiopulmonary bypass. A microscopical examination revealed that the tumor had the features of the chondrosarcoma originating in the pulmonary artery. There have been very few reports on chondrosarcoma in the pulmonary artery. It is reported that the prognosis of the sarcoma in the pulmonary artery is less favorable, however, this case had uneventfully postoperative course and no signs of recurrence one year after operation. PMID- 8473797 TI - [Prosthetic valve endocarditis after double valve replacement]. AB - This is a report of a patient who underwent re-AVR due to prosthetic valve endocarditis after double valve replacement (MVR, AVR). A 54-year-old female was admitted to other hospital on April 14, 1990, because of high fever, progressive anemia, and cardiomegaly. The patient was hospitalized to our department urgently with the diagnosis of prosthetic valve endocarditis. Arterial blood culture grew methicillin-resistant Staphylococcus epidermidis. Echocardiography showed a vegetation at the disc of the mechanical valve in the mitral position, but we could not find any vegetation or thrombus there at the reoperation, and the aortic mechanical valve seemed to be intact. Signs of inflammation continued to be positive after reoperation. On the 33rd hospital day, a diastolic murmur was heard, and emergency cardiac catheterization was done. Detachment of the prosthetic aortic valve and rupture of the sinus of Valsalva due to mycotic aneurysm, and the dissection of the aorta had occurred. We performed re-AVR and replacement of the ascending aorta. The patient died of multiple organ failure following drug-induced hepatic failure. It is suggestive that we missed the prosthetic aortic valve endocarditis during the reoperation. Our thoughts and introspections on the echocardiographic diagnosis of the prosthetic valve endocarditis after double valve replacement were discussed. PMID- 8473798 TI - [Myxoma originating from right ventricle found incidentally with cardiac murmur- a case report of surgical treatment]. AB - We report a rare case of a 21-year-old male who had myxoma originating from septal band of the right ventricle. He was otherwise healthy young man without any associated symptom. His cardiac murmur was found incidentally upon routine health control mass examination. Subsequently, echocardiography and angiocardiography demonstrated a tumor occupying the right ventricular outflow tract and protruding into the main pulmonary artery in systolic phase. He was operated upon using extracorporeal circulation. By right ventriculotomy the tumor was resected together with septal tissue 5 mm around the stalk, which branched into the myocardium. Resected mass was 4 x 3.7 cm in size and 5 grams in weight. Because of the frozen section of the surgical stump was positive for tumor cells, additional resection of septal myocardium was carried out. The defect was closed using mattress sutures with dacron felt strips. His postoperative course was uneventful. Thirty-two months after the surgery, patient has no sign of recurrence. Right ventricular myxoma is uncommon with only 27 cases appearing in Japanese literature. In review of literature, we discussed the characteristics and management of the right ventricular myxoma. PMID- 8473799 TI - [Successful surgical management for chronic sternal osteomyelitis and anterior mediastinal abscess after double valve replacement by total sternectomy and pectoralis major muscle flaps]. AB - A 63-year-old woman underwent double (aortic and mitral) valve replacement in February, 1987. Thirty days later, purulent drainage developed at the sternotomy incision with high fever. Wound cultures revealed staphylococcus aureus. She was treated by local wound care with antibiotics. About one month later, she had a satisfactory wound healing. But three cutaneous fistulas with discharge emerged at the sternotomy incision in November (9 months later) and the cultures grew the same species. The fistulogram showed the communication between these tracts and the mediastinum. The diagnosis of chronic sternal osteomyelitis and anterior mediastinal abscess was made. At first the resection of the xiphoid process and the mediastinal drainage were carried out in March, 1988. Inspite of this procedure, she still had persistent purulent discharge. Then, en bloc excision of the infected sternum and the adjacent costal cartilage were performed in April. The defect was obliterated with the bilateral pectoralis major muscle flaps. After the radical operation, her wound was completely healed, even though the ventilatory support was needed for 24 days because of flail chest due to the anterior chest wall instability. Now she has been free from recurrence for four years. Total sternectomy and pectoralis major muscle plombage seem to be a very effective management in chronic sternal osteomyelitis. PMID- 8473800 TI - [A case of Behcet's disease associated with ascending aortitis and aortic regurgitations--surgical repair with Cabrol's method]. AB - This is the case report of a 52 years old female patient operated with Cabrol's method for the inflammatory lesion of the aortic root in Behcet's disease. The diagnosis of incomplete type of Behcet's disease had already been established 4 years ago and the patient had been taking regular check-up since then. About one year ago, newly developed cardiac murmur compatible with aortic regurgitation was detected and the patient was subsequently referred to us for the surgical repair. Although aortic valve replacement (AVR) was attempted first, Cabrol's method was lastly chosen, since inflammatory features on the surface of the ascending aorta associated with slight aortic annular dilatation were observed during the procedure and it was easily anticipated that these might induce postoperative paravalvular leakage and pseudoaneurysm, if AVR were performed. Two weeks after the surgery, the patient developed aphthous stomatitis associated with several other evidences of inflammatory recurrence, the steroid therapy was instituted with prednisolone. Post operative progress was uneventful and the patient has been completely well at the 6th month after the surgery. In conclusion, it is strongly recommended the Cabrol's method should be chosen to prevent post operative unfavourable complications, whenever any evidence of inflammation is observed around the aortic root area. PMID- 8473801 TI - [Two cases of Morgagni's hernia]. AB - Two cases of Morgagni's hernia comprising protrusion of the omentum alone are reported. The treated patients were 65- and 63-year-old obese women. They were referred to our hospital because of chest pain or vomiting accompanied by abnormal shadow in right cardiophrenic angle on chest roentgenogram. Computed tomogram (CT) demonstrated a mass of fat density behind the sternum for the both patients. The first patient was diagnosed as Morgagni's hernia by pneumoperitoneum, and surgical repair was done by the transabdominal approach. Magnetic resonance imaging (MRI) was carried out for the second patient, and showed intrathoracic mass lesion which was continuous with the subphrenic tissue. Although the second patient was diagnosed as mediastinal lipoma, median sternotomy revealed that the mass lesion was Morgagni's hernia. Postoperatively, both patients recovered uneventfully. The Morgagni's hernia has been reported to be about 3% of all diaphragmatic hernia. This disease may be discovered either because it causes respiratory or gastrointestinal complaints, or because an abnormal shadow in right cardiophrenic angle on a chest roentgenogram. If air filled structures are present in the hernia, a barium study will confirm the diagnosis. In a case with a hernia containing only omentum, the diagnosis is difficult. CT has been regarded as the procedure of choice by several authors. The coronal and sagittal views of MRI can demonstrate the relationship between the herniated structures and the diaphragm, heart, pericardium. We emphasize the role of MRI for the diagnosis of Morgagni's hernia. PMID- 8473802 TI - [Total arch replacement for dissecting aneurysm using permanent bypass to the supra-aortic branches and left-heart bypass]. AB - The patient was a 36-year-old women with Marfan syndrome who had received graft replacement of ascending aorta for Stanford-type A dissecting aneurysm two years ago. She was re-operated on for residual arch and descending aortic dissection. We have found that it was Simple and effective to perform total arch replacement by using permanent bypass to the three principal supra-aortic branches and left heart bypass. PMID- 8473803 TI - [A case report of surgical treatment for aortic valve papillary fibroelastoma]. AB - A 71-year-old woman was referred to our hospital for aortic valve replacement because of the vegetation of aortic valve. She had transient right arm weakness and aphasia in November 1991. On two-dimensional echocardiogram, she was found to have a mobile, pedunculated mass attached to the non-coronary cusp of the aortic valve. At operation, multiple frond-like tumor measuring 7*7 mm was found attached to the free-edge of the non-coronary cusp of the aortic valve. The aortic valve with this tumor was excised and replaced with a 21-mm Carpentier Edwards prosthesis. Microscopic sections revealed the typical findings of a papillary fibroelastoma. The patient's postoperative course was unremarkable. PMID- 8473804 TI - [Simultaneous cesarean section and mitral valve replacement for infective endocarditis during pregnancy--a case report]. AB - Infective endocarditis (IE) during pregnancy is uncommon. A 31-week-pregnant, 21 year-old woman suffered from severe mitral regurgitation caused by IE. She fell into heart failure and threatened abortion. Following to cesarean section, an emergent mitral valve replacement with a bioprosthetic valve was successfully performed. Her postoperative recovery was uneventful and she was discharged home 30 days after the operation. Her baby, however, died of intracranial hemorrhage caused by hypoxia 171 days after delivery. A strategy of simultaneous open heart surgery and cesarean section is recommended when emergent open heart surgery is inevitable for the treatment of cardiac diseases in cases with 24 and/or more weeks' gestation. PMID- 8473805 TI - [Pseudo-false aneurysm of the left ventricle perforated into the right ventricle- a case report]. AB - A case of pseudo-false aneurysm of the left ventricle perforated into the right ventricle was reported. The patient was 60-year-old male with acute inferior myocardial infarction. Echocardiography showed a thin wall cavity on the apex of the right ventricle. Communication between the left ventricle and the right ventricle was detected on pulsed Doppler echocardiography. Surgery revealed a pseudo-false aneurysm in the free wall of the right ventricle communicating to both ventricles. We emphasize the importance of preoperative morphological and hemodynamic evaluation with Doppler echocardiography in the case of post myocardial infarction ventricular septal perforation. PMID- 8473806 TI - [Injury of pulmonary artery and intrathoracic artery--a surgical case report]. AB - The patient was a 52-year-old man. Tube drainage was performed to the right traumatic hemothorax. Then, 2,000 ml of blood flowed out and bleeding stopped for a time. Four hours later after injury, massive bleeding occurred again. So emergency thoracotomy was performed and we found a laceration in the main pulmonary artery and injury of intrathoracic artery. Pulmonary artery disruption from blunt chest trauma is rare. Further discussion was made by reviewing the related literature. PMID- 8473807 TI - [Isolated iliac aneurysms. Sixty-seven cases in forty-eight patients]. AB - 77 pure iliac aneurysms where detected in a group of 48 patients along a period of 21 years, and represented 12.3% of all patients having aortic, iliac, or aorto iliac aneurysms. The study group comprised 42 men and 6 women, 48-86 years old (mean 67.8 years). The aneurysm was located on the right side in 51.9%, on left side in 48.1%. The affection of the common iliac arteries (70.1%) was more frequent than it was on the internal iliac arteries (18.2%), or in the external iliac arteries (11.7%). The diameter was from 2 to 10 cms. 44 patients out of 48 (91.6%) where symptomatic, and 15 presented a rupture syndrome (31.3%). 10 patients (20.8%) had a pulsating mass. The etiology was unknown in 8 cases (16.7%); 2 patients had a mycotic aneurysm (4.2%). The remaining 38 patients (79.1%) had an aneurysm of atheromatous origin. 5 arteritic patients (10.4%) did not have any cure for their aneurysm, because it was considered threatening for 4 of them. The fifth patient was not treated because the artery was so calcified that it could not be clamped. A lumbar sympathectomy on the same side of the lesion was realised, in addition to the peripheral surgical act for arteritis. One patient had an endoaneurysmorrhaphy, another had an exclusion by ligature section of the aneurysm. For the remaining 41 patients (83.1%) the aneurysms where flattened, and vascular continuity was re-established by a prosthesis. 7 patients (12%) decreased post-operatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473808 TI - [Buerger's disease and juvenile arteriopathy. Analysis and classification based on a series of 127 cases]. AB - The prevalence and even the existence of Buerger's disease or thromboangiitis obliterans (TAO) are still ill-defined. The analysis of a continuous series of 127 young patients with obstructive arterial disease of the lower limbs (mean follow-up 67.7 months, lost to follow-up 13.8%) allows the evaluation of the clinical, radiological and evolutive characteristics of the patients. The positive diagnosis of TAO relies upon the four usual criteria: onset of the disease before 40, no other vascular risk factor than smoking, popliteal or infra popliteal arterial lesions, migrant superficial thrombosis. The patients are classified in 4 groups: Group I: undisputed TAO, presence of all the criteria, 13 cases (10.2%). Group II: probable TAO, presence of three criteria (no history of superficial thrombophlebitis), 19 cases (14.9%). Group III: tobacco-related atheroma, presence of two criteria (age under 40, no other risk factor than smoking), supra-popliteal lesions, 17 cases (13.4%). Group IV: precocious atheroma, presence of one criterium (age under 40), other risk factors, indifferent level of the arterial lesions, 78 cases (61.4%). The statistical analysis relies upon the comparison of the mean values for measurable parameters (Student-Fisher), for frequencies and percentages (Chi 2 Yates-Fisher) and upon a step by step discriminant analysis between groups I and IV, groups I and II and groups III and IV. The level of significance is 5%. The analysis points to two fundamental results: There is no significant difference either between groups I and II or between groups III and IV. Groups I and IV are significantly different for a lot of clinical, radiological and evolutive criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473809 TI - [General principles of medical care of the diabetic foot]. AB - In diabetic patients the foot is the focal point of neurologic, arterial and infectious complications. Affections of the foot are generally synonymous with a diabetic trophic disorder: the risk of gangrene is 17 times greater in diabetics than in non diabetics. Trophic disorders can affect the functional prognosis when they lead to amputation with subsequent altered weight bearing. They can provoke worsening of a subjacent arteriopathy, until then partially or totally asymptomatic, when the excision wound lacks the hemodynamic capacity for healing because of the associated arteriopathy. They can also induce local, regional (cellulitis) or even general (septicemia) infectious complications. They have a major socio-economic effect, by the loss of quality of life, the inability to work, and the cost of hospital and general care they engender. Finally, they have to be experienced by the patient and the treating team as a failure since, in the majority of cases, they imply an insufficient a priori knowledge of the predisposing factors: arteriopathy of legs and neuropathy with loss of sensitivity depriving the patient of the pain alarm signal if cutaneous lesions develop, and a delay in the recognition of triggering factors represented by microtrauma caused by shoes, particularly burns, frostbite or infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473810 TI - [Medical treatment of diabetic arteriopathy]. AB - Medical care of arteriopathy of leg in a diabetic patient involves control of diabetes combined with a series of non specific measures applicable to all atheromatous arteriopathies. Allowance must be made for the often silent nature of the arterial lesion, explicable by the associated peripheral neuropathy and the site of the lesions, generally more distal or staged than in non diabetics. A stable blood sugar level must be obtained to provoke improvement in hemorrheologic parameters and to slow the atheromatous process. A dietary regimen is associated with oral hypoglycemic agents or insulin therapy, the latter systematically for trophic disorders, administered as multiple injections or by insulin pump until complete healing is obtained. Insulin therapy normalizes abnormal blood lipid levels secondary to an uncontrolled diabetes. Other vascular risk factors (primary hyperlipoproteinemia, hypertension, smoking) must be allowed for. Of major importance in these patients at risk are foot hygiene, prevention of local trauma and correction of plantar anomalies. Aggravating factors in patients with arteritis are diabetic neuropathy and foot deformities. Regular walking is encouraged. Drug therapy (oral or injectable vasoactive agents, platelet antiaggregants, prostacyclin, normal blood volume restoration) depends on the severity of the arteriopathy and any complications. Analgesics are often required in advanced stages. Local therapy and sometimes antibiotics are necessary for trophic disorders. The frequent asymptomatic character up to the stage of gangrene should not, because of the diabetic diathesis, induce a wait and see attitude, and revascularization by angioplasty or shunt operation should be envisaged. A frequent complication of sugar diabetes, arteriopathy of the leg should be diagnosed early before it is revealed by a gangrenous lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473811 TI - [Treatment of diabetic arteriopathy. Importance of transluminal angioplasty]. AB - Results are reported of a retrospective analysis of transluminal angioplasty (TLA) interventions in 20 diabetic patients, 16 men and 4 women, mean age 56 years (range 32 to 82 years), with 24 dilated lesions, 16 patients having insulin dependent diabetes. In 12 cases the lesions were at the intermittent claudication stage, trophic lesions being present in 8 cases. Stenotic lesions were iliac (12 cases), superficial femoral (2 cases), popliteal (6 cases) and tibial (4 cases). One patient developed an acute occlusion following popliteal-anterior tibial recanalization, the only direct complication of the angioplasty. Angiography showed immediate satisfactory results in 22 of the 24 dilated lesions. Functional and hemodynamic improvement was a constant finding in patients with intermittent claudication, trophic lesions being healed in 4 cases (50%) the other patient showing either no change or requiring an unavoidable amputation (2 cases). These overall findings suggest that at the intermittent claudication stage no differences exist in the results of TLA when compared with a non diabetic population; inversely, in the presence of trophic disorders, the local conditions (distal bed, infection, gangrene) interfere considerably in the course of the dilatation. Transluminal angioplasty should therefore be carried out as early as possible in diabetics; arteriography should be performed as soon as even minimal claudication appears and, a fortiori, even at the onset of a trophic lesion. PMID- 8473812 TI - [Foot equipment of diabetic arteriopathy]. AB - Surgical appliances have a place of choice in the care of the foot with trophic lesions in diabetics, after partial amputation and as a preventive measure when it is free from trophic disorders. The type of appliance will depend on the footwear and the possibility of wearing orthopedic soles, whatever the stage of the affection. For the foot free from trophic disorders the shoes should be wide fitting, in soft leather and of the seamless type. Made to measure shoes should be reserved for badly deformed feet. The soles should be molded in silicone or polyurethane to distribute weight bearing and to avoid it over zones at risk. Appliances for the foot with trophic lesions should allow the resumption of walking. If the lesions are too extensive an orthosis is performed or a specific type of slipper with molded soles is worn to avoid pressure on the wounds. After amputation of toes a silicone orthoplasty is used to fill the interdigital space to avoid deformity of the other toes. If a front of foot has been amputated a corrected silicone molded sole with false extremity is applied. For a back of foot amputation an orthoprosthesis is made, preferentially in silicone introductible in a regular high sided shoe. In order to fulfil its preventive or temporary role, the appliance should evolve with time and be followed up regularly with close collaboration between the diabetic specialist the podologist and the orthotist. PMID- 8473813 TI - [Angioscopy of lower limb arteries. History and technique, cost and practical information]. AB - The historical background to angioscopy shows that the principal successes recorded by its use result from the miniaturization of fibroscopes and the progress in video imaging. The first tentative use of angioscopy was by surgeons during operations carried out at about 1970, that of percutaneous angioscopy dating from 1984. The material used for diagnostic (fibroscope, cinecamera, video system, flushing pump) and interventional (fibroscope, clamps, Dormia cage, endoprostheses ... ) angioscopy is such that the basic equipment requires an outlay of about 150 to 200,000 francs. Percutaneous angioscopy implies the insertion of a catheter allowing flushing of the arterial lumen by means of a pressurized perfusion pump which, when reversed, is transformed into an aspirating pump for removal of the clot and/or atheromatous debris. The procedure is simple and does not expose to more complications than conventional arteriography. PMID- 8473814 TI - [Percutaneous diagnostic angioscopy. Primary lesions]. AB - Efficacy of percutaneous treatments of arterial affections requires the correct choice of indications, necessitating precise knowledge of elementary arterial lesions. Arterial endoscopy appears to be more specific than angiography for this use, since it allows direct vision in vivo of the lesion, a histopathologic approach compared with the non univocal images produced by angiography (for example, an arterial obstruction can result from varied causes). Different accidents to the endothelial surface can be observed: golden yellow atheromatous elevations on a straw yellow background, intimal flaps, mobile intra-luminal vegetations. Established atheromatous stenosis are smooth and regular, or on the contrary ulcerated and edged with irregular flaps capable of provoking an eccentric residual lumen. The vegetating atheromatous lesions may project into the lumen, often as calcified and thus pearly white scales adhering to the wall, or as larger occlusive lesions. When capable of being isolated, a thrombus often completes the stenosis: its recognition is therefore fundamental since its removal exposes the subjacent lesions to be treated. The fresh clot is coral shaped, bright red and mobile in the blood flow. Established clots are compact and greenish brown. At an advanced stage of atheroma the surface of the occluding clot is covered with a regular straw yellow endothelium. In the presence of a dissecting vessel the fibroscope may be introduced into the false channel, no longer showing typical endothelium but a coagulated mass interspersed with fibrous bands. Prosthetic stenosis result from either intimal hyperplasia or a suturing fault with plication. PMID- 8473815 TI - [Interventional angioscopy]. AB - Since 1987, routine angioscopic examination has been performed in 191 patients undergoing angioplasty, with interventions (196) after a 2 year surveillance period (55). Angioscopy allowed follow up "de visu" of the performance of angioplasty, details of its mechanism to be precise and under dilatation to be carried out. For femoral artery occlusions it allowed treatment "a la carte": conventional dilatation of vegetating atheroma, specific treatment of established thrombi (5) and abstention from therapy of atheroma covered by endothelium (3). It also enabled fresh thrombi complicating a stenosis or at the origin of a thrombus to be detected. The extraction technique employed (15) is described. It facilitated catheterization by directing the probe, enabled avoidance of bypassing of stenosis and flaps and of dissection or false introduction into collaterals (10). Directed biopsy could be carried out in inflammatory arteritis (7). Vegetating atheromatous lesions could be opened and extracted, facilitating subsequent dilatation and allowing an approach to removal of iliac artery obstructions without major risks of complications (13). Finally, after an ineffective dilatation or the presence of a dissection, it assisted making the decision to introduce a stent (9), the tolerance and outcome of these stents are described. Or the 196 patients considered suitable for angioplasty, our therapeutic conduct was modified by angioscopy in 58 cases (29%). Not simply a new diagnostic tool, it plays a role in interventional vascular techniques. PMID- 8473816 TI - [Arterial hypertension, vascular remodelling and atherosclerosis]. AB - Therapy of essential hypertension (HT) should not imply the simple lowering of blood pressure alone but also reduction of the trophic effects provoked on the vascular system. Regression of left ventricular hypertrophy must be combined with "remodelling" of the overall arterial network to adapt to the abnormal physical forces acting on the vascular wall. This adaptive process has both qualitative and functional effects with structural modifications of the large arterial trunks as well as the smaller arteries, provoking adverse effects once they increase vascular resistance and diminish large artery compliance. Additionally, they tend to induce chronicity of HT, particularly since at the crossroad of these pathologic processes exist anomalies of endothelial secretory function. Treatment of HT should therefore comprise care of the vascular system, inasmuch as common mechanisms of cellular hypertrophy and proliferation are found in uncomplicated hypertension and atherosclerosis. PMID- 8473817 TI - [Importance of venous angioplasty in the treatment of subclavian venous thrombosis due to thoraco-brachial outlet syndrome]. AB - A patient with subclavian vein thrombosis was treated successfully by transluminal angioplasty after initial inefficacy of thrombolytic agents. Although employed previously in the treatment of intrinsic and extrinsic subclavian vein stenosis with variable results, this technique has not been used up to the present for the acute phase of thrombosis. Because of the presence of a thoraco-brachial outlet syndrome, the procedure was completed by a first rib resection. A control phlebography in forced abduction at two month follow up showed excellent permeability of the subclavian vein. PMID- 8473818 TI - [Cutaneous hemangioma associated with eosinophilia]. AB - A patient with a cutaneous angioma developed an intravascular coagulation syndrome with a eosinophilic leukocytosis and multiple arterial and venous thromboses affecting the vital prognosis. The possible role of the eosinophilia in the mechanism of complications is discussed. Local modifications in the angioma are suggestive signs preceding the onset of general thrombotic complications, their severity contrasting with the simplicity of the secondary surgical excision of the angioma. PMID- 8473819 TI - [A rare cause of claudication in a young person: cystic adventitial degeneration of the popliteal artery. Case study]. AB - The authors report a new case of cystic adventitial disease of the popliteal artery in a 43 year old woman. It is a rare disease in young people which concern essentially the adventitium of the arterial wall. When echographic aspect mimics thrombosed aneurysm aspect, the diagnostic is done by arteriography. Two surgical technics are convenient: the adventitiotomy and the venous bypass. PMID- 8473820 TI - [Treatment of superficial varicose phlebitis]. AB - The usual physical activity of the patient must be preserved when treating phlebitis of superficial varicosities, maintenance of the ability to walk about being an essential factor for a favorable outcome. Local and general anti inflammatory treatment of the initial acute phase of inflammation for less than one week improves the comfort of the patient and facilitates the application of the indispensable compression. Ambulatory thrombectomy can rapidly relieve pain, decompress the varicosities, accelerate revascularization and reduce the risk of residual pigmentation. To be simple and useful this procedure must be carried out before the fibrous organization of the clot. Stasis is controlled by an elastic stocking or bandage, the latter being often more effective and better tolerated initially. Compression must be maintained until elimination of the responsible varicose vein. Surgery and anticoagulants of all types are not indicated for treatment of uncomplicated superficial thrombosis, being indicated only in case of an authentic extension to the deep venous network. Surgery should then be limited to a safety crossectomy, heparins being reserved strictly for often prolonged preventive therapy or for treatment of a deep phlebitis. PMID- 8473821 TI - [Is it necessary to operate on small abdominal aortic aneurysms?]. AB - The indication for surgical treatment of aneurysms of 5 cm diameter or larger is no longer the subject of much debate but the problem still arises for aneurysms equal to or less than 4 cm in diameter. This problem is a real one since epidemiologic studies have shown the frequency of aortic aneurysms to be about 45/100,000 in men and 20/100,000 in women. The incidence of rupture in these small aneurysms is null for some authors, such as Nevitt, for those of less than 5 cm, but Crawford reported an incidence of 9%. Exceptionally, rupture may occur in ectatic aortitis with weakened walls. Small aneurysms are generally kept under observation and not operated upon immediately. The increase in size varies between 21 and 40 mm according to the patient. Apart from the size of the aneurysm a further factor to be allowed for is the presence or absence of an intramural clot. In addition to the possible role it can play in the course of the aneurysm itself it may be the source of an emboli, which, after rupture, are the cause of the second symptomatology of aortic aneurysms. Indications for surgery of small aneurysms should be restricted to those with large intramural aneurysms, those with irregular morphology of a segment possibly the site of weakening of the wall which can be detected by a scan or NMR imaging, without forgetting certain sacciform aneurysms suggestive of a mycotic etiology and requiring surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473822 TI - Application of corrosion cast method for scanning electron microscopic observation of mouse embryo vasculature. AB - We described a method for making vascular corrosion casts of mouse embryos and applied it to study the vasculature of the whole body mouse embryo at 13.5 days (body length 9-11 mm) to 18.5 days (body length 18-23 mm), as well as that of its respective organs. The Mercox resin was perfused via the umbilical vessels using a special needle made by pulling the hematocrit tube (caliber 100-200 microns). The specimens were treated with 10% NaOH, rinsed, dried, coated with gold and observed under a scanning electron microscope. Visceral organs of a 13.5 day embryo were rather immature, but the liver vasculature was relatively well developed. In a 15.5 day embryo, the whole body vasculature was relatively well developed and the features of respective organs could be identified. In a 18.5 day embryo, almost all organs and extremities were well developed, but sensory organs in some parts showed immature development. PMID- 8473823 TI - An improved technique for observing both membranous organelles and cytoskeleton in saponin-extracted cells. AB - Detergent-extraction of soluble cytoplasmic proteins under low osmotic pressure induces severe morphological damage, particularly on membranous organelles, although this processing is often required to observe cytoskeletal elements in the cells. In the present study, the osmotic adjustment of the rinsing solution and fixative, which were used after the detergent-extraction using saponin, has greatly improved the ultrastructure of membranous organelles. This improved method allowed us to observe both cytoskeletal elements and the fine structure of membranous organelles by electron microscopy. PMID- 8473824 TI - Monoclonal antibody enhancement of FSH-induced uterine growth in snell dwarf mice. AB - The enhancing effect of bovine FSH monoclonal antibody (bFSH-MAb) on the gonadotrophic activity of FSH was investigated in dwarf mice using a uterine weight bioassay. Increasing doses of bovine FSH (NIH-FSH-B1; 3.3, 10 or 30 micrograms/day) were administered for 5 days to dwarf mice (groups of five) with or without administration of a bFSH-MAb preparation (USDA-bFSH-MC28; 100 micrograms protein/day) which at a dilution of 1:15,000 bound 50% of 125I labelled bFSH (USDA-bFSH-BP3). The bFSH, at the doses given, gave no increases in uterine weight; when, however, these doses were given with bFSH-MAb, significant (three- to four fold) increases in uterine weight resulted. PMID- 8473825 TI - Declining sperm counts in men--is there an endocrine cause? PMID- 8473826 TI - The role of thyroidal type-I iodothyronine deiodinase in tri-iodothyronine production by human and sheep thyrocytes in primary culture. AB - We have studied the origin of tri-iodothyronine (T3) secreted by human and sheep thyrocytes in primary culture and also the expression of type-I thyroidal iodothyronine deiodinase (ID-I) in the thyroid and liver of man and various other animals. Inhibitors of ID-I reduced T3 secretion from human but not sheep thyrocytes. In contrast, inhibitors of de-novo thyroid hormone synthesis reduced both thyroxine (T4) and T3 production in sheep thyrocytes, but had no effect on the T3 secreted by human thyrocytes. Human thyrocytes did not produce T4 under the culture conditions used, although some endogenous T4 was present in the cells following their isolation. Although thyrotrophin (TSH) stimulated T3 production in both human and sheep thyrocytes, iodine in the form of potassium iodide was only essential for T3 and T4 production by the sheep cells. Although 125I from Na125I was incorporated into T3 and T4 in TSH-stimulated sheep thyrocytes, no 125I incorporation into T3 or T4 was detected in TSH-stimulated human thyrocytes. Using activity measurements and affinity labelling, ID-I was present in the livers of all species studied, but ID-I could not be detected in thyroid tissue from cattle, pigs, sheep, goats, rabbits, deer or llamas. In contrast, thyroid tissue from man, mice, guinea-pigs and rats had significant ID-I activity and expressed an affinity-labelled protein with a molecular mass of approximately 28.1 kDa on SDS-PAGE. These data show that under the culture conditions used, sheep thyrocytes produced T3 by de-novo synthesis, whilst human thyrocytes produced T3 by deiodination of endogenous T4. We conclude that thyroidal ID-I shows marked species difference in its expression and that, in those species which express the enzyme (man, mice, guinea-pigs and rats, in this study), it appears that it may make an important contribution to thyroidal T3 production. PMID- 8473827 TI - Specificity studies of particulate binding sites for steroid hormones in subcellular fractions of the porcine corpus luteum. AB - We have studied the binding of a number of radiolabelled steroids and lipophilic substances to porcine corpus luteum (CL) particulate fractions. Following preincubation of CL homogenates with radiolabelled progesterone or pregnenolone prior to fractionation on continuous sucrose density gradients, a broad peak of binding was observed associated with a particulate fraction of buoyant density 1.05-1.10 g/cm3. Progesterone content also peaked at a similar buoyant density (1.06-1.12 g/cm3). Pretreatment of luteal homogenates with digitonin perturbed the buoyant density of the progesterone-binding particulate fraction to 1.10-1.14 g/cm3 and sharpened the binding peak. Progesterone content was also perturbed to a similar extent by digitonin pretreatment, without release of the steroid. Oestrogens were also sequestered by this fraction, but steroid precursors (cholesterol, cholesterol ester), corticosteroids (cortisol, corticosterone), sterol conjugates (oestrone sulphate, pregnanediol glucuronide) and other lipophilic substances (arachidonic acid, phospholipid, prostaglandins E1, E2 and F2 alpha) were not bound. Androgens were bound weakly by fractions from control gradients but, in the presence of digitonin, significant binding could be demonstrated. Radiolabelled steroids were shown to interact directly with luteal membrane fractions, rather than interacting first with cytosolic steroid receptors which then bound to membranes. Furthermore, [3H]progesterone was not bound by porcine granulosa cell particulate fractions. These observations suggest that this fraction may be involved in sequestration or packaging of progesterone for secretion by the luteal cell. PMID- 8473828 TI - Sex steroids affect glucocorticoid response to chronic inflammation and to interleukin-1. AB - The influence of gender and sex hormones upon both the hypothalamic-pituitary adrenal (HPA) axis and the immune and inflammatory responses is well recognized, but it is not clear to what extent the two effects are interdependent. We have investigated this interaction using a chronic inflammation model. Corticosterone levels were measured in mature BALB/c male and female mice, which were intact, sham-operated or gonadectomized. No significant differences were found between groups in baseline corticosterone, but systemic inflammation (cotton-induced granulomas) resulted in stimulation of the HPA axis in a reproducible pattern. Corticosterone levels were higher in sham-operated females than in males, but gonadectomy had opposing effects in the two genders, resulting in reduced levels in females but significantly increased levels in males. A similar pattern emerged after stimulation by ether exposure or injection of interleukin-1 beta. In the chronic inflammatory model, replacement of ovariectomized females with physiological levels of progesterone restored a response similar to that of intact females. Physiological levels of 5 alpha-dihydrotestosterone prevented the increase in corticosterone levels caused by castration in males and also resulted in reduced corticosterone levels in sham-operated females. Oestradiol treatment did not affect corticosterone levels. Release of interleukin-1 by peritoneal macrophages from intact and gonadectomized mice with chronic inflammation followed a similar pattern, females releasing more than males. These data suggest a complex inter-relationship between sex steroids, inflammatory stimuli and the HPA axis, such that females have a greater tendency than males to generate activating signals and in addition have a greater sensitivity to such factors. PMID- 8473829 TI - Effects of growth hormone and thyroxine on kidney insulin-like growth factor-I and renal growth in hypophysectomized rats. AB - The effects of treatment for 11 days with human growth hormone (hGH; 140 micrograms/day), thyroxine (T4; micrograms/day) and hGH+T4 on renal growth and content of insulin-like growth factor-I (IGF-I) in hypophysectomized rats have been compared with saline-treated hypophysectomized animals and intact control animals. Right kidney weight and kidney weight/body weight ratio remained low in the saline-treated group (313 +/- 9 mg vs 694 +/- 28 mg in controls on day 11, P < 0.001 and 3.4 +/- 0.12 x 10(-3) vs 4.2 +/- 0.10 x 10(-3), P < 0.005 respectively). In T4- and hGH-treated animals, kidney weight gain was similar (to 420 +/- 14 and 450 +/- 22 mg on day 11 respectively, P > 0.05), whilst the increase was greater in the group given hGH+T4 (to 572 +/- 34 mg, P < 0.001 compared with hGH- and T4-treated groups). The kidney weight/body weight ratio became normal in the T4- and hGH+T4-treated animals but remained low in the hGH treated group. The renal content of IGF-I was low in the saline-treated animals throughout the study (92 +/- 10 ng/g on day 11 vs 219 +/- 8 ng/g in control animals, P < 0.001), but increased to a maximum of 88% above baseline on day 1 in the group given T4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473830 TI - Liposome-mediated macrophage depletion: an experimental approach to study the role of testicular macrophages in the rat. AB - Liposome-entrapped dichloromethylene diphosphonate was injected locally into the right testes of adult rats. This treatment, which has been found to deplete resident macrophages in some other organs, reduced the number of testicular macrophages by at least 90%. Testicular weight and seminiferous tubule morphology were unaffected by liposome treatment. Leydig cell testosterone secretion gradually declined in the macrophage-depleted testes, and there was a compensatory increase in Leydig cell size and testosterone secretion in the contralateral saline-injected testes. These observations suggest that macrophages influence Leydig cell function locally. It is concluded that liposome-mediated depletion of testicular macrophages may serve as an experimental model with which to study the physiological role of these cells. PMID- 8473831 TI - The human chorionic gonadotrophin-induced inflammation-like response is enhanced in macrophage-depleted rat testes. AB - Liposome-entrapped dichloromethylene diphosphonate (Cl2MDP) was injected locally into the right testes of adult rats in order to deplete testicular macrophages. The number of testicular macrophages in the treated testes was reduced by at least 90% at 7 and 14 days after treatment. Unilaterally testicular macrophage depleted animals were treated with 100 IU human chorionic gonadotrophin (hCG) subcutaneously and the inflammatory response was compared in the macrophage depleted and intact contralateral testis. Four hours after hCG treatment, intratesticular testosterone was similarly increased in intact and macrophage depleted testes. In macrophage-depleted testes there was a large increase in the number of leukocytes in testicular blood vessels and numerous leukocytes had migrated into the interstitial tissue. This response was greater than in the intact contralateral testis. It was concluded that testicular macrophages are probably not the origin of the inflammatory mediator secreted in the rat testis after hCG treatment. On the contrary, it appears that testicular macrophages may secrete factors inhibiting hCG-induced testicular inflammation. PMID- 8473832 TI - Paracrine effects via the epidermal growth factor receptor in the rodent testis may be mediated by non-Leydig interstitial cells. AB - The epidermal growth factor (EGF) receptor is expressed in a wide variety of cell types and is known to be present in the testis of many species including man. In the present study, specific 125I-labelled EGF binding was observed in isolated interstitial cell preparations from both the intact and Leydig cell-depleted rat testis. It was demonstrated that the population of cells to which 125I-labelled EGF binds has a different buoyant density from either of the two adult Leydig cell populations, and remains unchanged in the absence of Leydig cells following in-vivo treatment with ethane dimethane sulphonate (EDS). Cells of this density (1.064 g/ml) identified by electron microscopy were fusiform mesenchymal cells, identical to those suggested by others to be able to differentiate into Leydig cells in vitro, i.e. Leydig cell precursors. In a culture system using two interstitial cell preparations of different buoyant densities from immature rats, both EGF and transforming growth factor-alpha (TGF-alpha) caused increased [3H]thymidine incorporation in the less dense cell preparation. TGF-alpha was more potent than EGF. EGF increased testosterone production in both fractions in amounts which could be related to the amount of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)-positive cells. This study demonstrated that rat Leydig cells (defined as those cells which bind 125I-labelled human chorionic gonadotrophin, have distinct buoyant densities, are 3 beta-HSD positive and are sensitive to EDS), do not bind 125I-labelled EGF. Rather, EGF binds to a mesenchymal cell without LH receptors which is resistant to EDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473833 TI - Serum and urinary concentrations of sex hormones and genital swelling during the menstrual cycle of the gibbon. AB - The relationship between sex hormone concentrations and female genital swelling during the menstrual cycle in the monogamous gibbon was comparable with that of polygamous female primates, such as the chimpanzee, which live in multimale groups and have larger swellings. The data, therefore, support the hypothesis proposed by C. R. Carpenter more than 50 years ago, that the gibbon's genital swelling, like that of other female primates, reflects basic physiological processes associated with progress of the menstrual cycle. Genital swelling increased during the follicular phase with increasing concentrations of oestradiol and oestrone glucuronide, reached maximal swelling in association with the mid-cycle peaks in the oestrogens and LH and began detumescence with the initial increases in progesterone during the luteal phase. The data also suggest that the menstrual cycle of the gibbon is shorter than previously reported, since cycles of 19-22 days exhibited hormone patterns that are consistent with ovulation. The genital swelling of the female gibbon is a useful marker for monitoring progress of the menstrual cycle and the presumptive time of ovulation. PMID- 8473834 TI - The 11 beta-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats. AB - Steroid-metabolizing enzymes modulate the effects of androgens on brain differentiation and function, but no similar enzymatic system has been demonstrated for adrenocorticosteroids which exert feedback control on the hypothalamus. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) rapidly metabolizes physiological glucocorticoids (corticosterone, cortisol) to inactive products, thereby regulating glucocorticoid access to peripheral mineralocorticoid and glucocorticoid receptors in a site-specific manner. Using in-situ hybridization, we found expression of 11 beta-OHSD mRNA in neurones of the hypothalamic paraventricular nucleus (PVN) where corticotrophin-releasing factor-41 (CRF-41) is synthesized and from where it is released into hypophysial portal blood. Administration of glycyrrhetinic acid (GE), a potent 11 beta-OHSD inhibitor, decreased CRF-41 release into hypophysial portal blood in the presence of unchanged circulating glucocorticoid levels, suggesting that 11 beta-OHSD regulates the effective corticosterone feedback signal to CRF-41 neurones. These effects of GE were not observed in adrenalectomized animals, demonstrating dependence on adrenal products. In contrast, GE led to two- to threefold increases in arginine vasopressin and oxytocin release into portal blood, effects also dependent upon intact adrenal glands. These results suggest that 11 beta OHSD in the PVN, and possibly other sites, may represent a novel and important control point of corticosteroid feedback on CRF-41 release in vivo. PMID- 8473835 TI - The action of LH-releasing hormone and five analogues on oestradiol, oxytocin and vasopressin secretion by bovine granulosa cells in culture. AB - The release of oxytocin, arginine-8-vasopressin and oestradiol-17 beta by bovine granulosa cells in culture was analysed either with or without LH-releasing hormone (LHRH), its agonists (cyclo [Pro1DPhe6] LHRH and des 1-3, 10[DAla6] LHRH) or antagonists ([DPhe2DPhe6] LHRH, [DPhe2DPhe(NH2)6] LHRH or cyclo [Pro1DPhe2DPhe6] LHRH). All preparations used stimulated granulosa oxytocin and oestradiol secretion. Vasopressin release was significantly increased after all treatments with LHRH antagonists, but not after LHRH or its agonists. Our observations demonstrated a direct influence of LHRH and its analogues on the secretion of oestrogen and nonapeptide hormones by bovine granulosa cells. A comparison of the effects of LHRH, its agonists and antagonists suggests that the action of these peptides at the hypophysial and ovarian level is relatively independent. PMID- 8473836 TI - Serum levels of adrenal androgens up to adrenarche in Peruvian children living at sea level and at high altitude. AB - Serum levels of adrenal androgens were measured in children of both sexes living at sea level and at high altitude using a cross-sectional design. The levels were compared in relation to age at each altitude (150 m and 3400 m above sea level), and the first significant increase in mean levels compared with values at preceding ages was assessed and defined as adrenarche. A total of 118 boys and 95 girls aged 6-12 years living at low altitude and 95 boys and 104 girls aged 7-15 years living at high altitude, all of them attending public schools, were studied. Serum dehydroepiandrosterone, dehydroepiandrosterone sulphate and androstenedione were measured by radioimmunoassay and height and weight by standard anthropometric techniques. There were two significant increases in serum levels of adrenal androgens, the first observed in children between 6 and 8 years at sea level, and between 7 and 9 years at high altitude, and the second in children between 10 and 12 years at sea level and between 12 and 15 years at high altitude. Serum adrenal androgen levels increased earlier in children at sea level than at high altitude. It is concluded that adrenarche occurs later at high altitude than at sea level. PMID- 8473837 TI - Contextual processing of multidimensional and unidimensional auditory stimuli. AB - Stimulus context (the distribution of stimulus values) can strongly affect both perception and judgment. In 14 experiments, the method of magnitude estimation revealed 2 fundamentally different kinds of context effect in loudness. An assimilative effect dominated when stimuli varied unidimensionally (in intensity only). But a contrasting, or adaptation-like, effect dominated when stimuli varied multidimensionally (in frequency and intensity). In Experiment 15, direct loudness comparison revealed a potent, adaptational process specific to the signal frequency. Taken together, these and other results are compatible with the view that loudness perception and judgment reflect the net outcome of 2 different contextual processes: a relatively early (though probably not peripheral) process of perceptual adaptation and a later process of response-dependent assimilation. PMID- 8473838 TI - Common factors in the identification of an assortment of brief everyday sounds. AB - Acoustic, ecological, perceptual and cognitive factors that are common in the identification of 41 brief, varied sounds were evaluated. In Experiment 1, identification time and accuracy, causal uncertainty values, and spectral and temporal properties of the sounds were obtained. Experiment 2 was a survey to obtain ecological frequency counts. Experiment 3 solicited perceptual-cognitive ratings. Factor analyses of spectral parameters and perceptual-cognitive ratings were performed. Identification time and causal uncertainty are highly interrelated, and both are related to ecological frequency and the presence of harmonics and similar spectral bursts. Experiments 4 and 5 used a priming paradigm to verify correlational relationships between identification time and causal uncertainty and to assess the effect of sound typicality. Results support a hybrid approach for theories of everyday sound identification. PMID- 8473839 TI - Phonetic coherence in duplex perception: effects of acoustic differences and lexical status. AB - A modified version of duplex perception was used to investigate the nature of perceptual organization of speech. Ss were asked to identify stimuli in which a third-formant transition was presented to 1 ear and a full syllable (base) was presented to the other ear. Phonetic integration occurred even when the spectral composition or onset frequency of the isolated transition was varied relative to the base. However, when onset asynchronies were added to spectral differences, the isolated transition ceased to contribute to the syllable percept. Lexical status of the eventual phonetic percepts also influenced the phonetic integration of acoustic components into syllable percepts. These results suggest that combinations of low-level acoustic and phonetic differences between components and higher level lexical information interact to influence the grouping of acoustic components into phonetic percepts. PMID- 8473840 TI - Olfactory perception and olfactory imagery: a multidimensional analysis. AB - Whether a system of imagery for olfaction exists is currently an unsettled issue. Moreover, the dimensions underlying odor perception have eluded researchers for many years. Two experiments bearing on these issues are presented. In one experiment, a group of 32 undergraduates rated the similarity of pairs of 16 commonplace odorants (e.g., chocolate and leather) they perceived using scratch and sniff stimuli; in another, a different group of 44 undergraduates was asked to imagine and then rate the similarity of the same pairs of odors. Multidimensional scaling of the data suggests that three-dimensional solutions with similar stimulus dimensions, such as fruitiness, strength, and familiarity, underlied the ratings of both perceived and imagined odors. By finding that similar dimensions define the psychological space of both the imagery and the perception tasks, this study suggests that imagery does indeed exist for olfaction. PMID- 8473841 TI - Odor-intensity interaction in binary mixtures. AB - Four principles underlying odor summation in mixtures were examined on the bases of 10 Ss' magnitude estimates of 41 mixtures and their components (pyridine and DMDS). Thus, the overall intensity summation for mixtures are compared to self addition reflected by the power function for single substances: Hypoaddition is a characteristic of both. Compromise is found for 25% of the mixtures, but it is not inherent in the power function. No level dependency is found for mixtures, although it is in accordance with the power function. Asymmetrical summation exists for mixtures and is inconsistent with the power function. Therefore, the idea of a congruence in odor-intensity summation processes is rejected. The results also constitute a successful cross-validation of the angle alpha (99 degrees vs. 102 degrees) of the perceptual vector model reported by B. Berglund et al. (1973). PMID- 8473842 TI - Dual-task interference and the cerebral hemispheres. AB - It has been argued that dual-task interference is reduced when the two cerebral hemispheres can carry out the two tasks independently. Evidence for this idea has arisen from studies involving manipulations such as lateralized stimulation or response, or requiring mental operations believed to depend primarily on a particular hemisphere. However, these studies have typically involved a very limited degree of response uncertainty, which appears critical in producing the most extreme dual-task interference (the psychological refractory effect). Pairs of tasks with independent response uncertainty were examined, and various manipulations were used to promote hemispheric task separation. Dual-task interference was not modulated by these manipulations. It seems likely that response selection represents a central bottleneck, in the sense that this process cannot operate simultaneously and independently in the two hemispheres. PMID- 8473843 TI - What enumeration studies can show us about spatial attention: evidence for limited capacity preattentive processing. AB - Subitizing, the enumeration of 1-4 items, is rapid (40-120 ms/item) and accurate. Counting, the enumeration of 5 items or more, is slow (250-350 ms/item) and error prone. Why are small numbers of items enumerated differently from large numbers of items? It is suggested that subitizing relies on a preattentive mechanism. Ss could subitize heterogeneously sized multicontour items but not concentric multicontour items, which require attentional processing because preattentive gestalt processes misgroup contours from different items to form units. Similarly, Ss could subitize target items among distractors but only if the targets and distractors differed by a feature, a property derived through preattentive analysis. Thus, subitizing must rely on a mechanism that can handle a few items at once, which operates before attention but after preattentive operations of feature detection and grouping. PMID- 8473844 TI - The locus of inhibition in the priming of static objects: object token versus location. AB - The inhibition witnessed in the negative priming effect has been accounted for by positing an object file containing both identity and location information. In the present study, four experiments with 31 human subjects replicate the negative priming effect and, using new dual-target conditions where subjects respond to the target first perceived on a two-target forced-choice probe trial, suggest that location alone could account for the observed inhibition. Experiment 1 establishes an RT baseline for the new dual-target condition, whereas Experiments 2 and 3 replicate previously found single-target effects under dual-target conditions. Experiment 4 allows a concurrent determination of the inhibition accruing to both the target and distractor. The results are discussed relative to the likely existence of different kinds of inhibition which reveal themselves as a function of task demands. PMID- 8473845 TI - Skewed symmetry: a nonaccidental property used to perceive visual forms. AB - Mathematically, skewed symmetry is a nonaccidental property because it can be interpreted as bilateral symmetry in depth viewed from a nonorthogonal angle. To find out whether this is a useful property in the perception of visual forms, 4 experiments were designed in which the Ss had to determine whether 2 symmetric or random patterns were the same regardless of possible affine transformations between them. The results provided mixed evidence: Although there was always a large symmetry advantage, skewed symmetry was only perceived as bilateral symmetry in depth for dot patterns with higher order types of symmetry (Experiment 1), when the dots were connected to form closed polygons (Experiments 2 and 4), or when they were surrounded by a frame to enhance their planarity (Experiment 3). In other cases, Ss relied on local groupings on the basis of proximity or curvilinearity, which are qualitatively affine invariant. PMID- 8473846 TI - Dynamical constraints on pictorial action lines. AB - Pictorial action lines are an effective way of portraying movement in a static drawing. When such lines emanate from the backs of characters, they can give a sense of the path or style of movement. Seven experiments assessed whether photographic streak lines-lines that depict actual movement paths-can, in and of themselves, be informative about the act that produced them. Lines were produced as a darkly clad actor with point-lights attached to his major joints performed a number of actions in front of an open-lens camera. Completely naive Ss had little success identifying events in these photographs. Once Ss were told of the photographic technique, however, striking proficiency was achieved. Subtle distinctions (e.g., whether the movement was forward or backward or performed while wearing weights) were made for some of the events. Results are discussed in terms of various treatments of pictorial information. PMID- 8473847 TI - Coupling dynamics in interlimb coordination. AB - In 1:1 frequency locking, the interlimb phase difference phi is an order parameter quantifying the spatial-temporal organization of 2 rhythmic subsystems. Dynamical modeling and experimental analyses indicate that an intentional parameter phi psi (intended coordination mode, phi = 0 degrees or phi = 180 degrees) and 2 control parameters omega c (coupled frequency) and delta omega (difference between uncoupled eigen-frequencies) affect phi. An experiment was conducted on 1:1 frequency locking in which phi psi, omega c, and delta omega were manipulated using a paradigm in which a person swings hand-held pendulums. As delta omega deviated from 0, the observed phi deviated from the phi psi, indicating a displacement in the phi attractor point. The displacements were exaggerated by increasing omega c. The displacements were coordinated with a decrease in the stability of phi and with higher harmonics in power spectrum of phi. Implications of the results for modeling interlimb coordination are discussed. PMID- 8473848 TI - Production of polyrhythms. AB - Previous research has shown that there are strong constraints on the concurrent performance of nonharmonically related motor sequences such as polyrhythms. A model of polyrhythm production is proposed that involves a hierarchical timing system. The model assumes a single mechanism (a counter) for the timing and serial ordering of responses. Predictions derived from the model were tested in an experiment in which skilled (musically trained) and unskilled Ss attempted to reproduce polyrhythms of varying complexity. The results agreed with the model's predictions and showed that Ss adopted a hierarchical form of integrated motor organization in which movements of the slow hand were subordinate to movements of the fast hand. This strategy was consistent across S groups, polyrhythms, and hand arrangements. PMID- 8473849 TI - Intentionality in human gait control: modifying the frequency-to-amplitude relationship. AB - Tight frequency-to-amplitude relationships are observed in spontaneous human steady gait. If required, however, they can be modified. The following experiments were aimed at the processes underlying this flexibility, which forms the fundamental basis of the intentional adaptive capabilities of locomotion. In Experiment 1, Ss had to intentionally modify the frequency-to-amplitude relationship (leading to preferred or nonpreferred steady states). In Experiment 2, they had to temporarily perturbate the stride-frequency-to-amplitude relationship to intentionally shorten or lengthen 1 stride. Within the important constraints exerted by the head-arm-trunk system on leg movement, the results pointed out 2 main strategies that allow the S to intentionally adapt stride organization on-line: adjustment of the tonic properties of the oscillating leg to achieve nonpreferred steady states and phasic action to ensure temporary movement away from a steady state. PMID- 8473850 TI - Effects of sulfhydryl inhibitors on depolarizations-contraction coupling in frog skeletal muscle fibers. AB - We have studied the effects of the sulfhydryl reagents on contractile responses, using either electrically stimulated single muscle fibers or short muscle fibers that were voltage-clamped with a two-microelectrode voltage-clamp technique that allows the fiber tension in response to membrane depolarization to be recorded. The sulfhydryl inhibitors para-chloromercuribenzoic acid (PCMB) and parahydroximercuriphenyl sulfonic acid (PHMPS), at concentrations from 0.5 to 2 mM, cause loss of the contractile ability; however, before this effect is completed, they change the fiber contractile behavior in a complex way. After relatively short exposure to the compounds, < 20 min, before the fibers lose their contractile capacity, secondary tension responses may appear after electrically elicited twitches or tetani. After losing their ability to contract in response to electrical stimulation, the fibers maintain their capacity to develop caffeine contractures, even after prolonged periods (120 min) of exposure to PHMPS. In fibers under voltage-clamp conditions, contractility is also lost; however, before this happens, long-lasting (i.e., minutes) episodes of spontaneous contractile activity may occur with the membrane polarized at -100 mV. After more prolonged exposure (> 30 min), the responses to membrane depolarization are reduced and eventually disappear. The agent DTT at a concentration of 2 mM appears to protect the fibers from the effects of PCMB and PHMPS. Furthermore, after loss of the contractile responses by the action of PCMB or PHMPS, addition of 2 mM DTT causes recovery of tension development capacity. PMID- 8473851 TI - Anion modulation of taste responses in sodium-sensitive neurons of the hamster chorda tympani nerve. AB - Beidler's work in the 1950s showed that anions can strongly influence gustatory responses to sodium salts. We have demonstrated "anion inhibition" in the hamster by showing that the chorda tympani nerve responds more strongly to NaCl than to Na acetate over a wide range of concentrations. Iontophoretic presentation of Cl- and acetate to the anterior tongue elicited no response in the chorda tympani, suggesting that these anions are not directly stimulatory. Drugs (0.01, 1.0, and 100 microM anthracene-9-carboxylate, diphenylamine-2-carboxylate, 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonate, and furosemide) that interfere with movements of Cl- across epithelial cells were ineffective in altering chorda tympani responses to 0.03 M of either NaCl or Na acetate. Anion inhibition related to movements of anions across epithelial membranes therefore seems unlikely. The chorda tympani contains a population of nerve fibers highly selective for Na+ (N fibers) and another population sensitive to Na+ as well as other salts and acids (H fibers). We found that N fibers respond similarly to NaCl and Na acetate, with spiking activity increasing with increasing stimulus concentration (0.01-1.0 M). H fibers, however, respond more strongly to NaCl than to Na acetate. Furthermore, H fibers increase spiking with increases in NaCl concentration, but generally decrease their responses to increasing concentrations of Na acetate. It appears that anion inhibition applies to taste cells innervated by H fibers but not by N fibers. Taste cells innervated by N fibers use an apical Na+ channel, whereas those innervated by H fibers may use a paracellularly mediated, basolateral site of excitation. PMID- 8473852 TI - Primary structure, partial purification and regulation of key enzymes of the acetyl cycle of arginine biosynthesis in Bacillus stearothermophilus: dual function of ornithine acetyltransferase. AB - A 3.4 kb EcoRI fragment, cloned in E. coli, that carries part of a cluster of genes encoding arginine biosynthetic functions of the thermophilic bacterium Bacillus stearothermophilus, was sequenced on both strands. The sequence consists of a truncated argC gene, an argJ region encoding a polypeptide with both N acetylglutamate synthase and ornithine acetyltransferase activities, the argB gene and the N-terminal part of argD. The argB gene encodes a 258-amino-acid polypeptide with a deduced M(r) of 26918. A very high and thermostable N acetylglutamate 5-phosphotransferase activity was detected in extracts of E. coli arg B mutants transformed with the 3.4 kb fragment on a plasmid. A polypeptide band of M(r) 27,000 was detected by SDS-PAGE of heat-treated extract from such a strain. Both N-acetylglutamate synthase and ornithine acetyltransferase are encoded by the same 1290 bp open reading frame. The deduced sequence of 410 amino acids corresponds to a peptide of M(r) 43,349. The subcloned B. stearothermophilus argJ can complement a double argA argE E. coli mutant to prototrophy. Gel-filtration of a heat-treated extract of the complemented double mutant E. coli host showed that N-acetylglutamate synthase and ornithine acetyltransferase activities co-elute in a single peak corresponding to M(r) 110,000. Both activities were also heat-inactivated at the same temperature and strongly inhibited by ornithine. These results suggest that both activities can be ascribed to a single protein. PMID- 8473853 TI - Molecular and enzymological evidence for two classes of fumarase in Bacillus stearothermophilus (var. non-diastaticus). AB - The gene (fumABst) encoding an oxygen-labile fumarase of Bacillus stearothermophilus has been cloned and sequenced. The structural gene (1542 bp) encodes a product (FumABst) of M(r) 56,788 containing 514 amino acid residues. The amino acid sequence is 23% identical (37% similar) to FumA and FumB, the labile [4Fe-4S]-containing fumarases (Class I enzymes) of Escherichia coli. It exhibits no significant similarity to FumC and CitG, the stable fumarases (Class II enzymes) of E. coli and Bacillus subtilis (respectively). Enzymological studies indicated that FumABst resembles the iron-sulphur-containing fumarases in being dimeric (M(r) 2 x 58,500), oxygen labile and partially reactivated by Fe2+ plus DTT. The fumABst gene is the first gene encoding a Class I fumarase to be characterized in any organism other than E. coli. Enzymological and DNA hybridization studies further indicated that B. stearothermophilus resembles E. coli in containing an oxygen-stable fumarase (Class II enzyme). Sequence comparisons revealed significant similarities between the Class I fumarases and the products of adjacent open-reading frames (orfZ1 and orfZ2) located upstream of the macromolecular synthesis operon (rpsU-dnaG-rpoD) at 67 min in the E.coli linkage map. Located downstream of fumABst, there is an unidentified gene (orf2), which is homologous to the rhizobial nodB genes involved in the initiation of root nodule formation. PMID- 8473854 TI - Putrescine oxidase of Micrococcus rubens: primary structure and Escherichia coli. AB - The flavin adenine dinucleotide (FAD)-containing putrescine oxidase of Micrococcus rubens catalyses the oxidative deamination of putrescine. The amino acid sequences of the NH2-termini of the mature enzyme and lysyl-endopeptidase generated fragments were determined for preparation of synthetic oligonucleotides as hybridization probes for cloning. A 4.4 kb BamHI fragment which contained DNA sequences hybridizing to the probes was cloned in pUC19 in Escherichia coli. The nucleotide sequence together with the determined amino acid sequences revealed that this enzyme consists of 480 amino acids (M(r) 52,000) and contains an FAD binding consensus sequence at its NH2-terminal portion. In front of the transcriptional start point, which is 28 bases upstream of the initiation codon as determined by primer extension, -35 and -10 sequences similar to typical prokaryotic promoter consensus sequences are present. E. coli JM109 containing the putrescine oxidase gene just downstream of the lac promoter in pUC18 produced a large amount of this protein when grown at 37 degrees C but in the enzymically inactive form of inclusion bodies. However, cultivation of the recombinant E. coli cells at temperatures below 30 degrees C led to production of active enzyme (20 times as much as produced by the original M. rubens strain). PMID- 8473855 TI - Characterization of a calcium porter of Streptococcus pneumoniae involved in calcium regulation of growth and competence. AB - It is shown that Streptococcus pneumoniae possesses a Ca2+ transporter, sensitive to the amiloride derivative 2',4'-dimethylbenzamil (DMB), which is essential for grown at high Ca(2+)-concentrations, and which mediates the triggering by Ca2+ of competence for genetic transformation in the exponential phase and autolysis in the late exponential phase. DMB inhibited both Ca2+ transport and the Ca2+ response. Kinetic analysis of 45Ca2+ transport in ATP-depleted S. pneumoniae revealed an electrogenic influx sensitive to DMB. This transport was cooperative with respect to Ca2+ concentration, and exhibited a Hill coefficient (nH) of 2. In bacteria pre-loaded with 45Ca2+, a DMB-sensitive efflux could be triggered by an imposed Na+ gradient. The efflux kinetics showed the same cooperativity profile as Ca2+ concentration and a similar nH value to that of influx, suggesting a possible Na+/Ca2+ antiport. Cooperativity of transport was lowered (nH = 1) by a mutation that confers resistance to DMB and abolishes the Ca2+ response. These results demonstrate that DMB-sensitive Ca2+ transport is essential for growth and competence regulation. The role of the DMB-sensitive porter involved in Ca2+ circulation and in Ca2+ homeostasis and its possible regulation by competence factor are discussed. PMID- 8473856 TI - Further characterization of the assimilatory nitrate reductase from the yeast Candida nitratophila. AB - Nitrate reductase from the yeast Candida nitratophila was found to contain one molecule of cytochrome b557 and one atom of molybdenum per subunit. FAD/haem dependent diaphorase activity (haem domain) was associated with a 40 kDa tryptic fragment of the subunit. The 50 amino-terminal residues of this fragment were determined, and the sequence did not show significant similarity to deduced sequences of other nitrate reductases previously published. Increasing ionic strength in vitro had a stimulatory effect on enzymic activity via stimulation of the molybdenum-dependent terminal nitrate-reducing activity. Stimulation of activity by exogenous protein (bovine serum albumin or casein) also appeared to be an ionic effect. Stimulation of catalytic activity by phosphate was a separate effect. PMID- 8473857 TI - Purification and partial characterization of acid phosphatase from Candida lipolytica. AB - Non-specific acid phosphatase from Candida lipolytica cells was purified 111-fold by chromatography on DEAE-cellulose and gel filtration on Sephadex G-100 and Sepharose 4B. The enzyme is a glycoprotein containing 67% neutral sugars. The molecular mass of the highly purified acid phosphatase was found to be approximately 95 kDa by both SDS-PAGE and gel filtration. The pH and temperature optima were 5.8 and 55 degrees C, respectively. The enzyme was stable at pH values between 3.5 and 5.5 and at temperatures up to 60 degrees C. The purified phosphatase had a Km value of 3.64 mM for p-nitrophenyl phosphate and showed broad substrate specificity. PMID- 8473858 TI - Investigation of a killer strain of Zygosaccharomyces bailii. AB - The yeast Zygosaccharomyces bailii strain 412 was found to liberate a killer toxin (KT412) lethal to sensitive strains of Saccharomyces cerevisiae and Candida glabrata. Culture supernatants of the killer strain were concentrated by ultrafiltration and the extracellular protein was purified by gel filtration and ion-exchange chromatography. Gel filtration and SDS-PAGE of the electrophoretically homogeneous killer protein indicated an apparent molecular mass of 10 kDa. The killer toxin KT412 is probably not glycosylated since it did not show any detectable carbohydrate structures. KT412 was bound to sensitive but not to resistant yeast cells. The mannan, and not the glucan, fraction of the cell wall of the sensitive yeast was the primary target for the killer toxin binding. The killer strain Z. bailii 412 contained three double-stranded RNA plasmids of 1.9, 2.9 and 4.0 kb. Curing by cycloheximide resulted in the concomitant loss of killer activity and the 1.9 kb dsRNA species that is therefore regarded as equivalent to the killer-toxin-coding M-plasmids of S. cerevisiae. PMID- 8473859 TI - Saccharomyces cerevisiae has an inducible response to menadione which differs from that to hydrogen peroxide. AB - Exponential phase cells of Saccharomyces cerevisiae treated with the superoxide free-radical generating agent menadione (MD; 0.2 mM) for 60 min adapted to become resistant to the lethal effects of a higher concentration of MD (4 mM). Inhibition of protein synthesis by treatment with cycloheximide totally prevented the adaptation to MD, indicating that this is an inducible response completely dependent on protein synthesis; this differs from the situation with peroxide in which only some of the adaptive response is cycloheximide-sensitive. Cells subjected to heat shock (23 to 37 degrees C) or treatment with hydrogen peroxide (H2O2; 0.2 mM, 60 min) became more resistant to 4 mM-MD; however, MD pretreatment did not induce any thermotolerance or resistance to peroxide. These differences between the response to MD and H2O2 were reflected in the results of L [35S]methionine labelling studies. Using one-dimensional electrophoresis, only one polypeptide (60 kDa) was seen to be induced by 0.2 mM-MD and this was also induced by heat shock but not peroxide stress. With heat shock or peroxide treatment the induction of at least 10 polypeptides was detected using this approach. Using an isogenic petite strain, it was found that functional mitochondria were needed for conferring full resistance to MD, but that induction of the adaptive response was not dependent on mitochondrial function. PMID- 8473860 TI - Properties of genes involved in the control of isocitrate lyase production in Aspergillus nidulans. AB - The interaction between genes of Aspergillus nidulans conferring constitutive synthesis of isocitrate lyase (iclc A and iclcB) and fluoroacetate resistance (facB) has been investigated. Although facB mutants are unable to induce the glyoxylate cycle enzyme isocitrate lyase in response to acetate as sole carbon source, this phenotype was suppressed in recombinants of the type iclc;facB. The iclcA and iclcB mutations do not alter significantly the activities of eight enzymes of intermediary metabolism assayed. We conclude that the iclc genes are probably bona fide isocitrate lyase regulatory genes. PMID- 8473861 TI - Evaluation of a strategy for identifying nodulation competitiveness genes in Rhizobium leguminosarum biovar phaseoli. AB - Rhizobium leguminosarum biovar phaseoli strain KIM5s is consistently much more competitive than strain CE3 in nodulation of beans (Phaseolus vulgaris L.) in the laboratory and in the field. To identify genes that contribute to the competitiveness of KIM5s, we transferred a cosmid library containing KIM5s DNA into CE3 and applied the transconjugants to bean plants to allow the plants to enrich for those with enhanced nodulation competitiveness. The nodule isolates were then applied to plants for further enrichment. Of 75 isolates from nodules sampled after the two enrichments, 9 were more competitive than CE3. For example, when outnumbered in the inocula 40-fold by a reference strain, these nine strains typically occupied 15-40% of the nodules compared with 0-3% for CE3. However, when these strains were cured of the cosmids, they remained highly competitive, demonstrating that the enhanced competitiveness of the strains was not associated with the cosmids. We found no evidence for cosmid insertion into the chromosome or for cosmid-induced genetic changes in these cured strains. We found some evidence suggesting that their altered competitiveness was due to spontaneous genetic changes that did not involve the cosmids. Although these highly competitive variants remain genetically uncharacterized, they may provide insight into bacterial traits that contribute to, or detract from, successful nodulation competitiveness. PMID- 8473862 TI - A comparison of the multiple alleles of xylS carried by TOL plasmids pWW53 and pDK1 and its implications for their evolutionary relationship. AB - Both of the independently isolated TOL plasmids pWW53 and pDK1 contain multiple regions homologous to the xylS regulatory gene of the archetypal TOL plasmid pWW0. The three homologues on pWW53 vary in the extent of their homology to xylSpWW0, xylS1pWW53 is 99% identical to xylSpWW0 and is located relative to the single copy of xylRpWW53 in exactly the same way as xylS and xylR on pWW0. The DNA sequence of xylS3pWW53 is 87% identical to the xylSpWW0 sequence within the coding region but the non-coding DNA upstream is not homologous. There is a frame shift change at the end of the coding region which causes the C terminus of XylS3pWW53 to be extended by an additional 10 amino acids relative to XylSpWW0. xylS2pWW53 is anomalous and appears to encode a truncated pseudogene lacking the first 525 bases found in the other xylS genes. Evidence is presented to show that both xylS1pWW53 and xylS3pWW53 act as regulators of meta pathway operons. Plasmid pDK1 carries two homologues of xylS. xylS1pDK1 is functional and is a hybrid gene: its 5' end and the upstream sequences are highly homologous to both xylS1pWW53 and xylSpWW0, whereas its 3' end is identical to xylS3pWW53. The sequence of xylS2pDK1 is identical to that of the anomalous truncated xylS2pWW53. Comparison of the organization and the restriction maps of the xyl catabolic operons on pDK1 and pWW53, together with the nucleotide sequences presented here, indicates that the catabolic DNA on pDK1 has derived from a replicon on which the xyl genes are organized similarly to pWW53 and that a genetic rearrangement has taken place involving a reciprocal recombination internal to two of its xylS homologues. PMID- 8473863 TI - Cloning and sequencing of the gene which encodes the highly inducible acetamidase of Mycobacterium smegmatis. AB - The acetamidase of Mycobacterium smegmatis NCTC 8159 was purified, and the sequences of its amino-terminus and of two peptides obtained by proteolysis of the protein were obtained. A DNA fragment including the amidase structural gene was cloned in Escherichia coli, using oligonucleotide probes designed on the basis of the peptide sequences and a codon usage table calculated from published sequences of nine protein-antigen-encoding genes of the Mycobacterium tuberculosis complex. Sequence analysis of the cloned DNA revealed that the amidase gene encoded 406 amino acid residues. The nucleotide sequence close to and upstream of the amidase gene contained a probable ribosome-binding site but no identifiable promoter sequences. Three additional potential open-reading frames were found upstream of and very close to the amidase gene, with consensus '-35' and '-10' promoter sites between the first and second of these. It is hoped that the highly inducible expression of the acetamidase gene can be exploited to allow regulated expression of other genes cloned in mycobacteria. PMID- 8473864 TI - Characterization of two different types of resistance genes among producers of fortimicin-group antibiotics. AB - Fortimicin-A (FTM-A; astromicin)-resistance genes (fmr genes) isolated from six producers of the FTM-group of antibiotics were analysed. These genes could be classified into two types by the resistance profiles to aminoglycoside antibiotics and by their DNA homologies. Three genes, fmrT from the istamycin producer Streptomyces tenjimariensis ATCC 31603, fmrS from the sannamycin producer Streptomyces sannanensis IFO 14239 and fmrH from the sporaricin producer Saccharopolyspora hirsuta ATCC 20501, conferred resistance to FTM-A, kanamycin (Km) and neomycin B (Nm-B), but not to gentamicin (Gm). The other three genes, fmrO from the FTM-A producer Micromonospora olivasterospora ATCC 21819, fmrM from the antibiotic SF-2052 producer Micromonospora sp. SF-2098 (ATCC 31580) and fmrD from the dactimicin producer Dactylosporangium matsuzakiense ATCC 31570, conferred resistance to FTM-A, Km and Gm, but not to Nm-B. No DNA homology was detected between the two types of the resistance genes in Southern-blot analysis. The present results revealed that, in spite of the similarity of their biosynthesis genes, there are at least two different types of resistance genes among the FTM-group antibiotic producers. PMID- 8473865 TI - A macrolide-lincosamide-streptogramin B resistance determinant from Bacillus anthracis 590: cloning and expression of ermJ. AB - The inducible macrolide-lincosamide-streptogramin B resistance determinant, ermJ, from Bacillus anthracis 590 was cloned in Escherichia coli CSH26. The DNA sequence of ermJ was similar to that of ermK or ermD from B. licheniformis, suggesting that ermK-like genes have been distributed in Bacillus strains by transposition. Expression of ermJ was achieved in a B. subtilis minicell system, and the rRNA methyltransferase product of ermJ was purified. The molecular mass of the enzyme was 58 kDa, and it was concluded to be a homodimer. Its biochemical characteristics were different from those of ermC methyltransferase. PMID- 8473866 TI - Cell-surface location of Listeria-specific protein p60--detection of Listeria cells by indirect immunofluorescence. AB - A specific polyclonal antiserum was prepared against a gel-purified 60 kDa extracellular protein of Listeria monocytogenes ATCC 19111 corresponding to protein p60 previously detected in culture broths of L. monocytogenes strains Mackaness and EGD [Kuhn, M. & Goebel, W. (1989), Infection and Immunity 57, 55 61]. Indirect immunogold labelling combined with transmission electron microscopy and high-resolution scanning electron microscopy were used to investigate the location and distribution of p60 on the bacterial cell surface. In bacteria grown to the early stationary phase about 25% of the extracellular protein was estimated to be associated with the cell surface. The anti-p60 antiserum proved to be Listeria-specific. In an indirect immunofluorescence test the antiserum reacted with Listeria strains representing all species and different serotypes, except L. seeligeri, L. welshimeri, L. grayi and L. murrayi. No immunological cross-reactions were observed with 27 strains of bacteria from 16 other genera. The value of the anti-p60 antiserum in developing a diagnostic assay for Listeria cells in environmental samples and foods is discussed. PMID- 8473867 TI - Similarity in the EDTA-soluble antigens of Clostridium chauvoei and C. septicum. AB - The EDTA-soluble antigens were prepared from whole cells of six strains of Clostridium chauvoei and five strains of C. septicum and were compared by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis. SDS-PAGE profiles of the 11 strains were nearly identical, although there were slight variations in molecular mass in adjacent bands. In immunoblot analysis with two antisera against C. chauvoei and three against C. septicum, the antigens of all strains tested reacted with all five antisera and there were no differences in reactivities to the same antiserum between homologous and heterologous antigens. In an immunoblot reacted with a single antiserum, band patterns of 10 of the 11 strains were quite similar. After cross-absorption, antisera to both species lost most of their reactivities not only to heterologous antigens but also to homologous antigens. These results indicate that the two species share many common antigens and that there is a marked similarity in the antigenic properties of EDTA-soluble material. PMID- 8473868 TI - Calcium- and mucin-binding proteins of staphylococci. AB - The association of staphylococci with the mucus gel that overlays the mucosa of the respiratory tract may lead to clearance of cocci or, in certain conditions such as cystic fibrosis (CF), to colonization. In the present study, a quantitative radioassay was used to study the effect of Ca2+, which is elevated in CF sputa, on the adhesion of 3H-labelled Staphylococcus aureus to submaxillary gland mucin immobilized in MaxiSorp 96-well, break-apart modules. Ca2+ significantly enhanced the adhesion of S. aureus (five strains) and Staphylococcus epidermidis (four strains). The reaction was specific because adhesion was not enhanced in the presence of Mg2+, Ca(2+) + EGTA (a Ca2+ chelator) or protamine and was not attributable to hydrophobicity of the test strains. Staphylococcal adhesion was significantly (P < or = 0.005) blocked in the presence of highly sialated and sulphated reagents, which suggests that Ca2+ binds to the sialic acid and sulphate residues of immobilized mucin. The Ca(2+) binding sites on the surface of S. aureus were trypsin-sensitive; in addition, 125I-labelled solubilized S. aureus surface proteins reacted with immobilized mucin in a direct binding assay, and the reaction was significantly enhanced by Ca2+. Autoradiography demonstrated that 45Ca bound directly to two polypeptides (M(r) 170,000 and 150,000) of solubilized staphylococcal surface proteins separated by SDS-PAGE, and that 125I-labelled mucin bound directly to three staphylococcal polypeptides (M(r) 40,000, 35,000, and 29,000). These results suggest that S. aureus adhesion to mucin is mediated by at least two mechanisms: via Ca(2+)-binding surface proteins in the presence of Ca2+ and via mucin-binding surface proteins unrelated to Ca2+. PMID- 8473869 TI - Fusion of the genes encoding Escherichia coli heat-stable enterotoxin b (STb) and the maltose-binding protein to obtain mature STb enterotoxin. AB - The heat-stable enterotoxin b gene (estB) of Escherichia coli was fused to the gene for maltose-binding protein (malE). The estB gene was cloned into the pMAL-p vector using PCR. The construct consists of the signal sequence of maltose binding protein, which directs the export of the fusion protein to the periplasm, and the maltose-binding protein fused to the STb polypeptide. A sequence encoding a factor Xa cleavage site is present between malE and estB. The fused genes are controlled by Ptac, a strong inducible promoter. Following IPTG induction, the recombinant strain expressed a 47 kDa protein, which was easily purified from osmotic shock fluid by using preparative electrophoresis and electroelution. Cleavage of the fusion protein with factor Xa generated the maltose-binding protein (42 kDa) and a polypeptide of approximately 5 kDa, corresponding to the molecular mass of mature STb. A monospecific polyclonal rabbit antiserum raised against purified STb reacted in immunoblot with the fusion protein and the cleaved-off peptide. A positive response was observed when testing the osmotic shock fluid containing the fusion protein in a rat intestinal loop assay. On average, 3-4 mg of MBP-STb protein was recovered per litre of induced recombinant strain. PMID- 8473870 TI - Cloning, characterization and sequencing of two haemagglutinin genes from Eikenella corrodens. AB - Eikenella corrodens is emerging as an important human pathogen, in both extra oral and periodontal infections. From a clone bank of Eikenella corrodens chromosomal DNA produced in Escherichia coli JM109, twenty-two clones expressed Eikenella antigens and of these, two expressed functional haemagglutinins. By virtue of different restriction maps and a lack of homology by Southern hybridization, the two cloned fragments encoding the two haemagglutinins have been shown to be distinct. Maxicell analysis revealed that clone 1, carrying plasmid pVKR201, produces three Eikenella proteins, one of 31.5 kDa and two of approximately 14 kDa each. Expression of each of the proteins appears to be under the control of an Eikenella promoter(s). Clone 2, carrying plasmid pVKR301, produces two proteins, one of 93 kDa and the second of 17 kDa. Expression of both of these proteins in E. coli requires the lac promoter in the vector. By preparing a series of subclones and testing each by maxicell analysis and for haemagglutination activity, a functional map of the insert of clone 1 was deduced and the 31.5 kDa polypeptide identified as the haemagglutinin. Using similar methods, the 17 kDa protein was found to be the haemagglutinin of clone 2. The nucleotide sequences of both haemagglutinin genes were determined and are presented. Computer analysis revealed no homology between the two haemagglutinins, and no homology to any previously sequenced proteins. These are the first genes of this genus to be cloned and sequenced. PMID- 8473871 TI - Cloning and sequencing of two type 4 (N-methylphenylalanine) pilin genes from Eikenella corrodens. AB - Eikenella corrodens is a Gram-negative microaerophilic rod which is gaining recognition as an important human pathogen. We have previously reported the cloning and expression in Escherichia coli of a 3.6 kb Eik. corrodens genomic DNA fragment which encodes a 31.5 kDa haemagglutinin. Maxicell analysis revealed that this fragment also encodes two proteins of approximately 14 kDa. Nucleotide sequencing of the 2.2 kb fragment upstream of the haemagglutinin gene revealed two open reading frames with strong homology to genes encoding pilin subunit proteins of the type 4 or N-methylphenylalanine class. The two pilin genes, ecpA and ecpB, are complete and are expressed in E. coli. Southern analysis of ten additional Eik. corrodens strains revealed that all possess fragments homologous to ecpA. These data represent the first molecular evidence for pili in E. corrodens. PMID- 8473872 TI - Women and alcohol: use and abuse. AB - National surveys of the quantity/frequency of drinking, conducted over the last half century, show that the percentage of nonabstaining women has remained at about 60%. Although male/female differences in drinking are smaller than they were a generation ago, this appears to relate primarily to drinking by young adults. Study of social attitudes toward male and female intoxication has consistently indicated more disapproval of female intoxication. Alcoholism in women has a complex etiology that includes biological factors, positive family history, difficulties in impulse control, depression, and drinking by significant others in the social environment. Male/female differences in patterns and consequences of alcoholic behavior are summarized, as are differences among alcoholic women with earlier or later onset. PMID- 8473873 TI - The role of obstetric complications in schizophrenia. AB - The importance of obstetric complications in sporadic and familial psychoses was analyzed in 43 schizophrenic and 28 chronic schizoaffective patients. Patients and first-degree relatives were diagnosed using Research Diagnostic Criteria and the best-estimate procedure. Mothers of patients were interviewed for histories of pregnancy and obstetric complications in their offspring. Patients had more often suffered perinatal complications (42%) than their siblings (29%). The risk for obstetric complications and secondary cases of psychosis was enhanced in relatives of patients with a history of obstetric complications. Siblings with obstetric complications had a low incidence of psychoses; therefore, obstetric complications could not explain the occurrence of secondary cases of psychosis in siblings. Patients with familial psychoses had a higher incidence of obstetric complications than did sporadic cases (without reaching statistical significance). There was no inverse relationship between the history of obstetric complications in patients and the morbid risk of first-degree relatives for psychoses. The familial versus sporadic distinction revealed no subgroups where obstetric complications were of special relevance. PMID- 8473874 TI - Substance abuse in schizophrenia: service utilization and costs. AB - Utilization and cost of institutional and outpatient services were prospectively measured over 1 year for three groups of schizophrenic patients: current substance abusers, past substance abusers, and those without a history of substance abuse. Current abusers had significantly greater utilization and cost of institutional (hospital and jail) services. Current abusers also had greater utilization of emergency services. There were no significant differences between the groups in utilization and cost of other services, including psychosocial rehabilitation, outpatient treatment (case management, psychotherapy, and psychiatric visits), and housing supports. The implications for developing cost effective treatments for dually diagnosed individuals are discussed. PMID- 8473875 TI - Stability in backward masking performance in schizophrenics, affectively disturbed patients, and normal subjects. AB - The purpose of the present longitudinal study was to investigate the stability of backward masking performance in schizophrenics and nonschizophrenic psychotic patients. Twenty-two schizophrenics, eight nonschizophrenics, and 14 normal controls were tested three times, with an interval of 1 year between each test session. A standard stimulus duration procedure was used. The relative onset intervals between the target and the mask was 16.5 msec or 33 msec. A no mask condition was presented before the two masking conditions. Results showed that masking performance is a stable phenomenon, for both psychiatric groups and for normal controls. Significant differences were found between schizophrenics and the normal controls, but not between the two psychiatric groups. Vulnerability to masking stimuli as a specific characteristic for schizophrenics is, thus, not supported in the present study. The results suggest that backward masking deficit is an enduring feature of psychotic disturbances. PMID- 8473876 TI - The Defense Style Questionnaire. AB - The Defense Style Questionnaire has proven of interest as the first questionnaire to reliably describe defense styles. The 72-item DSM-III-R-labeled Defense Style Questionnaire was administered to 388 controls and 324 patients. Eight statistical and two a priori criteria were used in choosing two items to represent each of the 20 defenses. A new 40-item Defense Style Questionnaire is published together with normative and reliability data on a normal population, patients with anxiety disorders, and child-abusing parents. The scores are unaffected by the sex of the respondent, but the endorsement of immature defense styles decreases with age. PMID- 8473877 TI - Long-term mental sequelae of political imprisonment in East Germany. AB - This paper presents an assessment of the long-term mental sequelae of prolonged stress due to political persecution and imprisonment in the German Democratic Republic. Fifty-five former political prisoners with enduring psychiatric disorders were examined retrospectively in an exploratory study. The patients' experiences before, during, and after imprisonment were investigated using a semistructured interview. Psychopathological symptoms were assessed on clinical and self-rating scales; diagnostic classification was conducted according to DSM III-R. The patients had experienced serious trauma, including psychological torture, long-term imprisonment, and solitary confinement. We diagnosed a characteristic syndrome involving symptoms of depression and anxiety with vegetative complaints and increased arousal. In 35 (64%) patients, the symptoms persisted over an extended period without improvement. This syndrome resembles psychiatric disorders found after other forms of political persecution. It may be concluded that prolonged individually experienced political stress situations, even if they are not life-threatening, may have long-term mental sequelae. PMID- 8473878 TI - Prospective pilot study of survivors of torture and organized violence: examining the existential dilemma. PMID- 8473879 TI - Psychometric discrimination between anxiety and depression. PMID- 8473880 TI - Haem-peptide-protein interactions: Part 5. The haem undecapeptide microperoxidase 11 (Fe3+MP-11)/human serum albumin (HSA) reaction in aqueous methanolic solution. A simple system demonstrating the effect of hydrophobicity on ligand release from a ligand-protein complex. AB - Previous studies of the interaction of the haem undecapeptide (MP-11) with lipidated human serum albumin in aqueous solution have been extended to a range of MeOH/H2O solution compositions. It is demonstrated that the kinetic mechanism for the interaction does not change from a simple second- and first-order reversible scheme as XMeOH is increased, however while k1--the association rate constant is essentially invariant with XMeOH, K-1 increases some 600-fold over the range studied. The result is interpreted in terms of increased solvational stabilization of MP-11 and transition state as XMeOH increases and it is noted that the system provides a simple demonstration of the effect of hydrophobicity on facilitating transported ligand release from ligand/carrier protein molecules. PMID- 8473881 TI - The transport of aluminum and water across the rat small intestine. AB - Aluminum transport across the epithelium of the rat small intestine has been investigated to determine factors affecting its absorption and its effect on the transport of other substances across the membrane. The intestines were attached to a perfusion apparatus and perfused with Krebs-Ringer-bicarbonate buffer containing aluminum. The transport of aluminum and buffer ions across the small intestine were measured. Phosphate transport was found to be the most satisfactory marker for viability. It is impossible to accurately measure the aluminum transport across a biological membrane unless the aluminum concentration of the solution is stable over the period of measurement. Hence, the solutions were stabilized with citrate ions which made them stable over a period of at least two hours. The velocity of transport of aluminum across the epithelium increased steadily and only became constant after about one hour. The steady state value of 0.12 micrograms atom of Al/hr/mg dry tissue compares well with that reported in the literature for stable aluminum solutions. Aluminum inhibited the transport of water across the membrane, but the inhibition took about two hours to reach a steady state of about 50% of the control value. This indicates that aluminum-containing medications and foods are able to interfere with the absorption of nutrients from the gut. Aluminum salts may therefore be useful to prevent rapid dehydration in the treatment of certain diseases such as cholera. PMID- 8473882 TI - Cytotoxic and cytostatic activity of copper(II) complexes. Importance of the speciation for the correct interpretation of the in vitro biological results. AB - The cytotoxicity of some copper(II) compounds against the mouse cancer cell line B16, murine L929, human KB cells, and fibroblasts was investigated. All the copper(II) systems tested were shown to have pronounced toxicity against transformed cells and a cytostatic effect against untransformed cells, i.e., human fibroblasts. A careful speciation of the actual in vitro conditions reveals that copper(II) is essentially present as mixed complexes formed with the amino acids of the culture medium, [Cu(glutamine)(histidine)] being the main species. It was found that the cytotoxic activity is related to the amount of copper(II) contained in the tested compounds. PMID- 8473883 TI - The inhibition of corrinoid-catalyzed oxidation of mercaptoethanol by methyl iodide: mechanistic implications. AB - The cobalamin coenzymes (5'-deoxyadenosyl- and methylcobalamin) and their cobinamide counterparts (5'-deoxyadenosyl- and methylcobinamide) catalyze the oxidation of 2-mercaptoethanol to its disulfide with hydrogen peroxide formation under aerobic conditions. The reactions are blocked by methyl iodide. Inhibition by methyl iodide is apparently due to the formation of the trans dialkyl corrinoids: methyl(adenosyl)cobalamin, dimethylcobalamin, methyl(adenosyl)cobinamide, and dimethylcobinamide, respectively. When the reaction system is illuminated with visible light, inhibition is released and a dramatic enhancement in the rate of oxygen consumption occurs. For reactions catalyzed by adenosyl- and methylcobalamin and then inhibited by methyl iodide, the rates observed during photolysis approach those obtained with aquacobalamin. For reactions catalyzed by adenosyl- and methylcobinamide and then inhibited by methyl iodide, the rates observed during photlysis approach those obtained with diaquacobinamide. Thus, both trans axial carbon-cobalt bonds in the putative dialkyl corrinoid are homolyzed during photolysis. In contrast to these results, the catalysis of the aerobic oxidation of 2-mercaptoethanol by aquacobalamin is only weakly inhibited by methyl iodide. This observation suggests that aquacob(II)alamin is produced during the catalysis of this reaction. Superoxide, the anticipated product of the reaction between aquacob(II)alamin and dioxygen, is formed during aquacobalamin-catalyzed 2-mercaptoethanol oxidation since superoxide dismutase decreases the rate of oxygen consumption by 50%. However, the enzyme has no effect on oxygen uptake during reactions catalyzed by cobalamin coenzymes and their cobinamide counterparts. These corrinoid catalysts apparently transfer two electrons to dioxygen from cobalt(I) intermediates formed during the reactions. Nitrogenous bases inhibit corrinoid-catalyzed thiol oxidation by competing with 2-mercaptoethanol for axial-ligand coordination sites on the catalyst. In contrast to the inhibition observed with methyl iodide, visible light has no effect on the inhibition obtained with nitrogenous bases. PMID- 8473884 TI - Some potential antitumor 2,2'-dipyridylamine Pt(II)/Pd(II) complexes with amino acids: their synthesis, spectroscopy, DNA binding, and cytotoxic studies. AB - Four new palladium(II) and platinum(II) complexes of formula [M(dipy)(AA)]+ (where dipy is 2,2'-dipyridylamine, AA is an anion of glycine or L-alanine, and M is Pd(II) or Pt(II)) have been synthesized and characterized with amino acids binding as bidentate ligands. These complexes are 1:1 electrolyte in conductivity water. Of the above four complexes, the two L-alanine complexes show ID50 values against P388 lymphocytic leukemia cells lower than cis diamminedichloroplatinum(II), whereas the two glycine complexes show ID50 values higher than cisplatin. The interaction of calf thymus DNA with the above complexes shows significant spectral changes in the presence of [Pt(dipy)(gly)]Cl, [Pd(dipy)(ala)]Cl, and [Pt(dipy)(ala)]Cl and the mode of binding between these complexes and DNA seems to be noncovalent. PMID- 8473885 TI - Cortical pyramidal neurone loss may cause glutamatergic hypoactivity and cognitive impairment in Alzheimer's disease: investigative and therapeutic perspectives. PMID- 8473886 TI - Differential effects of a phorbol ester on carboxypeptidase E in cultured astrocytes and AtT-20 cells, a neuroendocrine cell line. AB - Cultured astrocytes have been shown to secrete various neuropeptides and the neuropeptide processing enzyme, carboxypeptidase E (CPE). The secretion of CPE enzymatic activity from astrocytes has been shown previously to be increased approximately twofold by treatment with tetradecanoylphorbol 13-acetate (TPA), a phorbol ester. In this study, metabolic labeling with [35S]Met was utilized to examine the effect of TPA on the biosynthesis of CPE protein in cultured astrocytes and in AtT-20 cells, a pituitary-derived cell line. Treatment of astrocytes with 0.1 micrograms/ml TPA for 24 h caused an 80% increase in the level of radiolabeled CPE in both the media and the cells, indicating that the synthesis of CPE was stimulated by the TPA. AtT-20 cells also secreted more radiolabeled CPE in response to TPA, but this increase was offset by a proportional decrease in the cellular level of radiolabeled CPE, and synthesis of CPE was not stimulated in this cell line. Northern blot analysis demonstrated that 0.1 micrograms/ml TPA elevated CPE mRNA by approximately 50% in cultured astrocytes but not in AtT-20 cells. Quantitative in situ hybridization studies demonstrated that the TPA-induced increase in CPE mRNA expression was largely due to increases in the number of cells expressing CPE mRNA, although for astrocytes from some brain regions the average level of CPE mRNA per cell was also elevated by TPA. These results suggest that astrocytes can be induced to express CPE, which is consistent with a role for astrocytes in intercellular signaling. PMID- 8473887 TI - Ammonium injection induces an N-methyl-D-aspartate receptor-mediated proteolysis of the microtubule-associated protein MAP-2. AB - We have shown previously that chronic hyperammonemia increases, in brain, the polymerization of microtubules that is regulated mainly by the level and state of phosphorylation of microtubule-associated protein 2 (MAP-2). Activation of the N methyl-D-aspartate (NMDA) receptor dephosphorylates MAP-2. Because we have found that acute ammonia toxicity is mediated by the NMDA receptor, we have tested the effect of high ammonia levels on MAP-2 in brain. Microtubules isolated from rats injected intraperitoneally with 6 mmol/kg ammonium acetate showed a marked decrease of MAP-2. Also, the amount of MAP-2 in brain homogenates, determined by immunoblotting, was markedly reduced, presumably by proteolysis. The content of MAP-2 was decreased by approximately 75% 1-2 h after ammonium injection and returned to normal values after 4 h. Proteolysis of MAP-2 was prevented completely by injection of 2 mg/kg MK-801, a specific antagonist of the NMDA receptor, suggesting that proteolysis is mediated by activation of this receptor. L-Carnitine, which protects rats against ammonia toxicity, also prevented MAP-2 degradation. Because activation of the NMDA receptor increases [Ca2+]i, we determined whether rat brain contains a Ca(2+)-dependent protease that selectively degrades MAP-2. We show that there is a cytosolic Ca(2+)-dependent protease that degrades MAP-2, but not other brain proteins. The protease has been identified tentatively as calpain I, for it is inhibited by a specific inhibitor of this protease. Our results suggest that ammonium injection activates the NMDA receptor, leading to an increase in [Ca2+]i, which activates calpain I. This, in turn, selectively degrades MAP-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473888 TI - CBP-18, a Ca(2+)-binding protein in rat brain: tissue distribution and localization. AB - The distribution of a novel calcium-binding protein with a molecular mass of 18 kDa (CBP-18) in the rat brain was studied by means of biochemical methods and immunohistochemistry on cryostat-sectioned tissue and compared with staining patterns of parvalbumin on adjacent sections. The biochemical analysis revealed high levels of CPB-18 in cortex and cerebellum, low levels in the lungs, and undetectable levels in all other tissues tested. Immunohistochemically, the polyclonal rabbit-derived antibody for CPB-18 showed selective affinity with periglomerular cells and dendrites in the olfactory bulb. Distinct immunostaining of scattered cells and their proximal dendrites was found in the anterior olfactory nuclei and in the perirhinal and entorhinal cortex. Strong staining of neuropil with recognizable but diffusely outlined cells was observed in the retrosplenial cortex, central amygdala, hippocampal rudiment, septum, area preoptica, hypothalamus, colliculus superior, and parabrachial nuclei. The cerebellum showed strong neuropil staining of both the molecular and the granule cell layer. Less intense neuropil staining and a few scattered cells were found in the neocortex, the remaining basal forebrain, and in the entire brainstem. Immunoreactivity was barely detectable or missing in the striatum, the hippocampus, the thalamus, and in the colliculus inferior. Thus, CPB-18 shows a unique staining pattern in the CNS, different from all other Ca(2+)-binding proteins studied so far. PMID- 8473889 TI - Beta-amyloid protein precursor and tau mRNA levels versus beta-amyloid plaque and neurofibrillary tangles in the aged human brain. AB - To learn whether or not the levels of beta-amyloid protein precursor (APP) and tau mRNAs are related to the formation of beta-amyloid and neurofibrillary tangles, we quantified these mRNA levels in three cortical regions of 38 aged human brains, which were examined immunocytochemically for beta-amyloid and tangles. Marked individual variabilities were noted in APP and tau mRNA levels among elderly individuals. The mean APP mRNA level was slightly reduced in the beta-amyloid plaque (+2) group, but not in the plaque (+) group, compared to the plaque (-) group. Some brains in the plaque (-) group showed increased APP expression, the extent of which was not seen in the plaque (+) or (+2) group. The differences in the mean tau mRNA levels were not statistically significant among the tangle (-), (+), and (+2) groups. These results show that beta-protein and tau deposition do not accompany increased expression of the APP and tau genes, respectively, and thus suggest that factors other than gene expression may be at work in the progression of beta-amyloid and/or tangle formation in the aged human brain. PMID- 8473890 TI - Ethanol-induced aspartate and taurine release from primary astrocyte cultures. AB - Exposure of primary astrocyte cultures to isosmotic ethanol from 10-100 mM led to both swelling of the cells and release of [3H]taurine and D-[3H]aspartate. Exposure to hyperosmotic ethanol, in the same concentration range, caused neither swelling nor release. Release was inhibited by the anion transport blocker L 644,711, already shown to inhibit amino acid release evoked by hypoosmotic or high-potassium medium, conditions that also cause astrocytic swelling. Ethanol induced release generally showed a decline in response to successive exposures to ethanol, and release was not dependent on extracellular calcium. Thus, the characteristics of swelling-induced release of amino acids by isosmotic ethanol seem to correspond to those of swelling-induced release from astrocytes due to exposure to hypotonic or high-K+ media. We discuss whether such effects may contribute to CNS damage after head injury and stroke. PMID- 8473891 TI - YM-09151-2 but not l-sulpiride induces transient dopamine release in rat striatum via a tetrodotoxin-insensitive mechanism. AB - The effects of the selective dopamine D2 receptor antagonists YM-09151-2 and l sulpiride on the in vivo release of dopamine (DA), L-3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in rat striatum were investigated. The drugs were injected into the striatum through a microinjection needle attached to a dialysis probe. YM-09151-2 (0.1 or 1.0 microgram/0.5 microliter) injected into the striatum produced a dramatic rapid-onset transient increase in striatal DA release in a dose-dependent manner. However, the DA increase induced by l sulpiride (15 or 75 ng/0.5 microliter) was small and of slower onset. An increase of DOPAC levels by YM-09151-2 was biphasic: The first peak occurred at 40 min, followed by a delayed-onset gradual increase. Slower-onset gradual increases were also found in DOPAC levels after l-sulpiride injection and in HVA levels after injections of both YM-09151-2 and l-sulpiride. The infusion of tetrodotoxin (TTX; 2 microM) revealed two different types of DA release mechanisms: The rapid-onset transient DA release induced by YM-09151-2 was TTX insensitive, whereas the slower-onset DA release induced by l-sulpiride was TTX sensitive. Moreover, the rapid-onset transient DA release was Ca2+ independent and was not affected by pretreatment with l-sulpiride or nomifensine. Therefore, it is concluded that YM 09151-2 injected into the striatum produced a transient striatal DA release that is independent of D2 receptors and the action potential. PMID- 8473892 TI - Casein kinase II activity in the postischemic rat brain increases in brain regions resistant to ischemia and decreases in vulnerable areas. AB - Casein kinase II (CKII) is a protein kinase acting in the intracellular cascade of reactions activated by growth factor receptors, and that has a profound influence on cell proliferation and survival. In this investigation, we studied the changes in the activity and levels of CKII in the rat brain exposed to 10, 15 and 20 min of transient forebrain ischemia followed by variable periods of reperfusion. The cytosolic CKII activity decreased during reperfusion by approximately 30 and approximately 50% in the selectively vulnerable areas, striatum and the CA1 region of the hippocampus, respectively. In the resistant CA3 region of hippocampus and neocortex, the activity increased by approximately 20 and approximately 60%, respectively. The postischemic changes in CKII activity were dependent on the duration of the ischemic insult. The levels of CKII did not change after ischemia, suggesting that the enzyme is modulated by covalent modification or is interacting with an endogenous inhibitor/activator. Treatment of the cytosolic fraction from cortex of rats exposed to ischemia and 1 h of reperfusion with agarose-bound phosphatase decreased the activity of CKII to control levels, suggesting that CKII activation after ischemia involves a phosphorylation of the enzyme. The correlation between postischemic CKII activity and neuronal survival implies that preservation or activation of CKII activity may be important for neuronal survival after cerebral ischemia. PMID- 8473893 TI - Catecholamines are present in a synaptic-like microvesicle-enriched fraction from bovine adrenal medulla. AB - "Synaptic-like microvesicles" are present in all neuroendocrine cells and cell lines. Despite their resemblance to small synaptic vesicles of the CNS, a thorough biochemical characterization is lacking. Moreover, the subcellular distribution of synaptophysin, the most abundant integral membrane protein of small synaptic vesicles, in adrenal medulla is still controversial. Using gradient centrifugation, we were able to compare the distribution of several markers for small synaptic vesicles and chromaffin granules. Synaptophysin was found at a high density (1.16 g/ml), purifying away from dopamine beta hydroxylase and cytochrome b561. Both noradrenaline and adrenaline showed a parallel distribution with synaptophysin, suggesting their presence in synaptic like microvesicles. Experiments in the presence of tetrabenazine did not influence the catecholamine content. Additionally, tetrabenazine binding showed a consistent shoulder in the region of synaptophysin. [3H]Noradrenaline uptake was blocked by tetrabenazine, but not by desipramine. Also chromogranin A parallels the distribution of synaptophysin; however, a localization in the Golgi cannot be ruled out. Synaptophysin was shown to undergo very fast phosphorylation, together with another triplet protein of approximately 18 kDa. In contrast, the latter showed a rather bimodal distribution coinciding with synaptophysin and dopamine beta-hydroxylase. Immunoelectron microscopy of synaptic-like microvesicle fractions showed an intense labeling for synaptophysin on 60-90-nm organelles. Whereas abundant gold labeling for cytochrome b561 was found over the entire surface of chromaffin granules, synaptophysin labeling was encountered mostly on vesicles adsorbed to granules. We conclude that catecholamines might be stored in synaptic-like microvesicles of the chromaffin cell. PMID- 8473894 TI - Opioid peptides in the rabbit carotid body: identification and evidence for co utilization and interactions with dopamine. AB - The rabbit carotid body is a catecholaminergic organ that contains dopamine and norepinephrine in a proportion of nearly 5:1. Chronic (15 days) carotid sinus nerve denervation or superior cervical ganglionectomy did not modify the carotid body dopamine content (5-6 nmol/mg of protein, equivalent to 250 pmol per carotid body), but sympathectomy reduced by approximately 50% the norepinephrine content. The carotid body has also a very high content of opioid activity (250 equivalent pmol of Leu-enkephalin/mg of protein) as measured by a radioreceptor assay that detects preferentially delta-opioid activity. In the carotid body the degree of opioid posttranslational processing to low-molecular-weight peptides (mostly Leu- and Met-enkephalin) is nearly 80%. HPLC identification of opioid peptides revealed that the sequences of Met- and Leu-enkephalin were in a proportion of nearly 6:1, indicating that the main opioid precursor in the carotid body is proenkephalin A. Chronic denervations of the carotid body did not modify the levels or the degree of opioid precursor processing. Acute hypoxic exposure of the animals (8% O2 in N2; 3 h) resulted in a parallel decrease of dopamine and opioid activity, without any change in the degree of opioid processing. Norepinephrine levels were not affected by hypoxia. These findings suggest corelease of dopamine and opioids during natural hypoxic stimulation. In agreement with the analytical data, [D-Ala2, D-Leu5]enkephalin, but not [D-Ala2,N Me-Phe4,Gly5-ol]-enkephalin, reduced the in vitro release of dopamine induced by low PO2, a high external K+ concentration, and dinitrophenol. Naloxone augmented the release response elicited by low PO2 stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473895 TI - Effects of chronic hypoxia on opioid peptide and catecholamine levels and on the release of dopamine in the rabbit carotid body. AB - Carotid body catecholamine and opioid levels were measured in rabbits exposed for 8 days to an atmosphere of 11% O2 in N2 (PO2 of approximately 80 mm Hg) and during an identical period of recovery, i.e., after 8 days of returning to the control normoxic atmosphere. Carotid bodies show a decrease in dopamine content at day 2. Thereafter, the levels of this biogenic amine increase progressively to peak at day 10, that is, 2 days after returning to a normoxic atmosphere. Finally, dopamine levels start to decrease and reach prehypoxic control levels at day 16, that is, after 8 days of recovery. In contrast, levels of native opioid peptides remain unchanged during the whole duration of the experiment, except for a decrease at day 2 of the hypoxic exposure. Levels of total opioid peptides are also below control values at day 2 of hypoxia, increase above control values on returning to a normoxic atmosphere (maximal levels at days 10-12), and later decrease to reach prehypoxic levels at day 16. As a result of these changes the ratios of dopamine to opioid levels show a progressive increase from day 0 to day 10 of the experiment and then return to control prehypoxic values. Carotid bodies isolated from animals that have been exposed to hypoxia for 8 days synthesize [3H]dopamine from its natural precursor [3H]tyrosine at a rate of 175 pmol/mg of protein/h, which is about double the rate of synthesis found in the carotid bodies of control animals and those allowed to recover for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473896 TI - Cellular localization of transforming growth factor-alpha mRNA in rat forebrain. AB - The cellular localization of transforming growth factor-alpha (TGF alpha) mRNA in juvenile and adult rat forebrain was examined using in situ hybridization with a 35S-labeled cRNA probe. TGF alpha cRNA-labeled neuronal perikarya were distributed across many forebrain regions including the olfactory bulb, caudate putamen, nucleus accumbens, olfactory tubercle, ventral pallidum, amygdala, hippocampal stratum granulosum and CA3 stratum pyramidale, and piriform, entorhinal, and retrosplenial cortices. TGF alpha cRNA-hybridizing cells were also localized to several thalamic nuclei and to the suprachiasmatic, dorsomedial, and ventromedial nuclei of the hypothalamus. In addition, labeled cells were present in regions of white matter including the corpus callosum, anterior commissure, internal and external capsules, optic tract, and lateral olfactory tract. Thus, both neurons and glia appear to synthesize TGF alpha in normal brain. Hybridization densities were greater in neuronal fields at 2 weeks of age compared with the adult, suggesting a role for TGF alpha in the development of several forebrain systems. Our results demonstrating the prominent and wide-spread expression of TGF alpha mRNA in forebrain, combined with the extremely low abundance of epidermal growth factor mRNA in brain, support the argument that TGF alpha is the principal endogenous ligand for the epidermal growth factor receptor in normal brain. PMID- 8473897 TI - Methamphetamine-induced dopamine overflow and injury to striatal dopamine terminals: attenuation by dopamine D1 or D2 antagonists. AB - Pharmacological blockade of either D1 or D2 dopamine (DA) receptors prevents damage of striatal DA terminals by repeated doses of methamphetamine (m-AMPH). Because the substantial DA overflow produced by multiple m-AMPH treatments appears to contribute to the subsequent injury, we have investigated the effects of blockade of D1 or D2 receptors on m-AMPH-induced DA efflux using in vivo microdialysis. Four treatments with m-AMPH (4 mg/kg, s.c., 2-h intervals) produced large increases in striatal DA overflow, with particularly marked overflow (10 times the basal values) following the fourth injection. Administered by themselves, four injections of the D1 antagonist SCH 23390 or the D2 antagonist eticlopride (0.5 mg/kg, i.p., 2-h intervals) significantly increased striatal DA overflow. However, treatment with either SCH 23390 or eticlopride 15 min before each of four m-AMPH injections attenuated the marked DA peak otherwise seen after the fourth m-AMPH injection. These effects on DA overflow were related to subsequent DA depletions. Although our m-AMPH regimen produced a 54% reduction in striatal DA tissue content 1 week later, pretreatments with either the D1 or the D2 antagonist completely prevented subsequent DA content depletions. Furthermore, the DA content of striatal tissue remaining 1 week after m-AMPH treatment was significantly correlated with the magnitude of the cumulative DA overflow during the m-AMPH treatment (r = -0.69). Thus, the extensive DA overflow seen during neurotoxic regimens of m-AMPH appears critical to the subsequent neurotoxicity, and the neuroprotective action of DA receptor antagonists seems to result from their attenuation of stimulant-induced DA overflow. PMID- 8473898 TI - Characterization of tritiated noradrenaline release from the rat preoptic area with microdialysis in vivo. AB - Present techniques are unable to provide a sensitive and accurate index of noradrenergic activity in the rat preoptic area. In this study, we have examined the brainstem A1 noradrenergic input to the preoptic area using a new technique whereby [3H]noradrenaline is preloaded into the preoptic area and release of radioactivity from this region is measured subsequently using microdialysis in vivo. Electrical stimulation of the ipsilateral A1 area for 20 min at 5, 10, and 15 Hz evoked significant increases in dialysate radioactivity that were repeatable and frequency-dependent. After removal of calcium from the perfusion medium, basal release of radioactivity was markedly reduced and the effect of A1 stimulation abolished. Changing to a 100 mM K+ medium evoked an increase in the release of radioactivity that was sixfold greater than that seen after A1 stimulation. Separation of the dialysate with HPLC showed that 33% of the increase in measured radioactivity after A1 stimulation was directly attributable to [3H]noradrenaline and the remainder to the metabolites vanillylmandelic acid, 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylglycol. In contrast, the increase in radioactivity after K+ depolarization was due almost completely to [3H]noradrenaline. Addition of 10 microM clonidine to the perfusion medium markedly reduced basal release of radioactivity, but had no effect on evoked release following A1 stimulation. Conversely, perfusion with 10 microM yohimbine had no effect on basal release, but significantly increased evoked release after A1 stimulation. These results now provide a characterization of noradrenergic activity in the preoptic area and indicate the importance of the A1 noradrenergic input to this region. The technique of measuring radioactivity with microdialysis after preloading with [3H]noradrenaline provides a relatively simple, sensitive index of noradrenergic activity in vivo with good temporal resolution. PMID- 8473899 TI - Elevated stimulatory and reduced inhibitory G protein alpha subunits in cerebellar cortex of patients with dominantly inherited olivopontocerebellar atrophy. AB - Although guanine nucleotide binding proteins (G proteins) are one of the critical components of signal transduction units for various membrane receptor-mediated responses, little information is available regarding their status in brain of patients with neurodegenerative illnesses. We measured the immunoreactivity of G protein subunits (Gs alpha, Gi alpha, Go alpha, Gq/11 alpha, and G beta) in autopsied cerebellar and cerebral cortices of 10 end-stage patients with dominantly inherited olivopontocerebellar atrophy (OPCA) who all had severe loss of Purkinje cell neurons and climbing fiber afferents in cerebellar cortex. Compared with the controls, the long-form Gs alpha (52-kDa species) immunoreactivity was significantly elevated by 52% (p < 0.01) in the cerebellar cortex of the OPCA patients, whereas the Gi1 alpha concentration was reduced by 35% (p < 0.02). No statistically significant differences were observed for Go alpha, Gi2 alpha, G beta 1, G beta 2, or Gq/11 alpha in cerebellar cortex or for any G protein subunit in the two examined cerebral cortical subdivisions (frontal and occipital). The cerebellar Gs alpha elevation could represent a compensatory response (e.g., sprouting, reactive synaptogenesis) by the remaining cerebellar neurons (granule cells?) to neuronal damage but also might contribute to the degenerative process, as suggested by the ability of Gs alpha, in some experimental preparations, to promote calcium flux. Further studies will be required to determine the actual functional consequences of the G protein changes in OPCA and whether the elevated Gs alpha is specific to OPCA cerebellum, because of its unique cellular pattern of morphological damage, or is found in brain of patients with other progressive neurodegenerative disorders. PMID- 8473900 TI - Regulation of protein kinase C activity by sensory deprivation in the olfactory and visual systems. AB - Environmental regulation of sensory function has provided an important model of plastic mechanisms mediating neural information processing. To define potential commonalities in information processing in different systems, we investigated molecular changes elicited by sensory deprivation in the developing rat olfactory and visual systems. Protein kinase C (PKC), an intracellular messenger implicated in synaptic plasticity and memory, was analyzed. Initial, developmental studies indicated that PKC activity in the soluble and particulate fractions of the olfactory bulb increased three- to fourfold from birth to 3 months of age. Unilateral olfactory deprivation prevented the developmental increase in both soluble and particulate PKC activities in the ipsilateral olfactory bulb and piriform cortex, the second-order relay. Phorbol ester binding localized PKC to intrinsic neuronal populations and their dendrites in the control and deprived bulbs. Moreover, PKC was similarly lower in the visual cortex of dark-reared rats than in light-reared controls. The changes in PKC were region specific, as activity was unchanged by either treatment in the parietal cortex, a control area that does not process primary olfactory or visual information. Our results suggest that the important intracellular messenger, PKC, is similarly regulated in entirely different sensory systems by different environmental stimuli. Consequently, different sensory systems may use common molecular mechanisms to process information. PMID- 8473901 TI - Complex interactions among second messenger pathways, steroid hormones, and protooncogenes of the Fos and Jun families converge in the regulation of the nerve growth factor gene. AB - Regulation of the expression of the nerve growth factor (NGF) gene has been reported previously to be mediated via the protooncogene c-fos. Activation of the protein kinase C pathway and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has also been reported to increase the pool of NGF transcripts in L929 fibroblasts. Here we show that activation of the cyclic AMP second messenger pathway antagonized the effect of phorbol 12-myristate 13-acetate (PMA) or serum on NGF synthesis, whereas it enhanced that of 1,25(OH)2D3. A positive effect was also observed when serum, PMA, and 1,25(OH)2D3 were added together, but dexamethasone reduced this enhancement. There was no close correlation between the increase in c-fos mRNA and that in NGF mRNA, suggesting that expression of the c-fos protooncogene is not necessarily followed by induction of the NGF gene. Rather, these two genes are simultaneously, and not sequentially, induced after forskolin treatment. It appears that regulation of the NGF gene depends on a repertoire of multiple regulatory AP-1 complexes arising from activation of the second messenger pathways. This suggests that NGF gene expression is under the control of a complex interplay among second messenger pathways, protooncogenes, and steroid hormones such as 1,25(OH)2D3 and glucocorticoids. PMID- 8473902 TI - Developmental changes in expression of a 60-kDa somatostatin receptor immunoreactivity in the rat brain. AB - The neuropeptide somatostatin (SRIF) exerts several important physiological actions in the adult CNS through interactions with membrane-bound receptors. SRIF expression is developmentally regulated and this regulation is most apparent in the cerebellum, where SRIF immunoreactivity is expressed at early postnatal ages and then disappears toward adulthood. The transitory nature of SRIF expression at a time of major changes in cerebellum suggests that this peptide may have a role in cerebellar development. To further investigate the role of the SRIF transmitter system during development, we have examined the levels of expression of SRIF receptors in the developing rat brain by immunoblotting using antiserum selective for a 60-kDa brain SRIF receptor. In whole rat brain, SRIF receptor immunoreactivity first appears at embryonic day 13 (E13), is elevated at E16, increases at birth, peaks at early postnatal ages, and then gradually declines with age. No apparent changes in size of the receptor occur with age. No consistent changes in levels of SRIF receptor immunoreactivity are detected from early postnatal ages to adulthood in the hippocampus, cerebral cortex, and striatum, but levels gradually decline in the hypothalamus. In contrast, SRIF receptor immunoreactivity is expressed transiently in cerebellum. SRIF receptor immunoreactivity is detectable in cerebellum at E16, increases in levels at birth, is apparent from postnatal day 3 to postnatal day 8, and then disappears. The transitory nature of SRIF receptor expression in cerebellum is unique and parallels the expression of SRIF immunoreactivity in this brain region. These findings support the hypothesis that SRIF has a role in cerebellar development. PMID- 8473903 TI - Effect of chronic estradiol and progesterone treatments of ovariectomized rats on brain dopamine uptake sites. AB - Dopamine released from brain nerve terminals is mainly removed from the synaptic cleft by an uptake mechanism. Despite their functional importance, modulation of the dopamine uptake sites is still not well known. Steroid hormones were shown to modulate brain dopamine transmission. The aim of this study was thus to investigate in ovariectomized rats the effects of 17 beta-estradiol and progesterone treatments on brain dopamine uptake sites. Treatments consisted of 17 beta-estradiol (10 micrograms/0.2 ml), progesterone (0.72 mg/0.2 ml), 17 beta estradiol + progesterone, or the vehicle (0.3% gelatin in saline solution) twice daily for 2 weeks. The steroid treatments left the affinity of [3H]GBR 12935 binding to striatal homogenates unchanged (ovariectomized rats, 0.823 +/- 0.028 nM), whereas the density was increased by these steroids alone or in combination to a similar extent of 16-23%. Chronic treatment of ovariectomized rats with 17 beta-estradiol, progesterone, or their combination increased to the same extent and uniformly [3H]-GBR 12935 binding in the striatum as measured by autoradiography; the increase was similar in the substantia nigra pars compacta, whereas no steroid effect was observed in the nucleus accumbens and in the substantia nigra pars reticulata. In summary, chronic exposure to 17 beta estradiol and/or progesterone increased dopamine uptake site density in the nigrostriatal dopaminergic system, whereas the nucleus accumbens and the substantia nigra pars reticulata were unaffected. PMID- 8473904 TI - Locally synthesized phosphatidylcholine, but not protein, undergoes rapid retrograde axonal transport in the rat sciatic nerve. AB - Retrograde axonal transport of phosphatidylcholine in the sciatic nerve has been demonstrated only after injection of lipid precursors into the cell body region. We now report, however, that after microinjection (1 microliter) of [methyl 3H]choline chloride into the rat sciatic nerve (35-40 mm distal to the L4 and L5 dorsal root ganglia), time-dependent accumulation of 3H-labeled material occurred in dorsal root ganglia ipsilateral, but not contralateral, to the injection site. The level of radioactivity in the ipsilateral dorsal root ganglia was minimal at 2 h after isotope injection but was significantly increased at 7, 24, 48, and 72 h after intraneural isotope injection (n = 3-8 per time point); at these time points, all of the radiolabel in the chloroform/methanol extract of the ipsilateral dorsal root ganglia was present in phosphatidylcholine. The radioactivity in the water-soluble fraction did not show a time-dependent accumulation in the ipsilateral dorsal root ganglia as compared with the contralateral DRGs, ruling out transport or diffusion of precursor molecules. In addition, colchicine injection into the sciatic nerve proximal to the isotope injection site prevented the accumulation of radiolabel in the ipsilateral dorsal root ganglia. Therefore, this time-dependent accumulation of radiolabeled phosphatidylcholine in the ipsilateral dorsal root ganglia is most likely due to retrograde axonal transport of locally synthesized phospholipid material. Moreover, 24 h after injection of both [3H]choline and [35S]-methionine into the sciatic nerve, the ipsilateral/contralateral ratio of radiolabel was 11.7 for 3H but only 1.1 for 35S, indicating that only locally synthesized choline phospholipids, but not protein, were retrogradely transported. PMID- 8473905 TI - Nine residues influence the binding of alpha-bungarotoxin in alpha-subunit region 185-200 of human muscle acetylcholine receptor. AB - Identification of residues in the skeletal muscle nicotinic acetylcholine receptor (AChR) that bind snake venom alpha-neurotoxin antagonists of acetylcholine [e.g., alpha-bungarotoxin (alpha-BTx)] provides structural information about the neurotransmitter binding region of the receptor. Using synthetic peptides of the human AChR alpha-subunit region 177-208, we previously localized a pharmacologically specific binding site for alpha-BTx in segment 185 199. To define in more detail the residues that influence the binding of alpha BTx to this region, we prepared 16 peptide analogues of the alpha-subunit segment 185-200, with the amino acid L-alanine sequentially replacing each native amino acid. Circular dichroism spectroscopy did not reveal changes in the secondary structure of the peptides except for the analogue in which Pro194 was substituted with alanine. This implies that any change in alpha-BTx binding could be attributed to replacement of the native residue's side chain by alanine's methyl group, rather than to a change in the structure of the peptide. The influence of each substitution with alanine was determined by comparing the analogue to the parental sequence alpha 185-200 in solution-phase competition with native human AChR for binding of 125I-labeled alpha-BTx. The binding of alpha-BTx by analogue peptides with alanine substituted for Tyr190, Cys192, or Cys193 was greatly diminished. Binding of alpha-BTx to peptides containing alanine replacements at Val188, Thr189, Pro194, Asp195, or Tyr198 was also reduced significantly (p < 0.003). An unanticipated finding was that substitution of alanine for Ser191 significantly increased alpha-BTx binding (p < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473906 TI - Rat brain glyceraldehyde-3-phosphate dehydrogenase interacts with the recombinant cytoplasmic domain of Alzheimer's beta-amyloid precursor protein. AB - Abundant senile plaques are a histological hallmark in the brain of Alzheimer's disease patients. Such plaques consist of, among many other constituents, aggregated beta A4 amyloid peptide. This peptide is derived from an amyloid precursor protein (APP) by irregular proteolytic processing and is considered to be involved in the development of Alzheimer's disease. To study possible interactions of brain proteins with beta A4 amyloid or other fragments of APP, beta A4 amyloid and beta A4 amyloid extended to the C-terminus of APP were recombinantly produced as fusion proteins termed "Amy" and "AmyC," respectively. Using Amy and AmyC affinity chromatography, a 35-kDa protein from rat brain was isolated that bound tightly to AmyC but not to Amy, thus indicating an interaction of the protein with the C-terminus of APP. This 35-kDa protein was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Binding of GAPDH to AmyC but not to Amy was confirmed by gel filtration. Although AmyC slightly reduced the Vmax of GAPDH, the same reduction was observed in the presence of Amy. These findings suggest that the interaction of the cytoplasmic domain of APP with GAPDH is unlikely to influence directly the rate of glycolysis but may serve another function. PMID- 8473907 TI - Difference in the effectiveness of Ca2+ to evoke catecholamine secretion between adrenaline- and noradrenaline-containing cells of bovine adrenal medulla. AB - Differential adrenaline (Ad) and noradrenaline (NA) secretions evoked by secretagogues were investigated using digitonin-permeabilized adrenal chromaffin cells, cultured adrenal chromaffin cells, and perfused adrenal glands of the ox. In digitonin-permeabilized cells, Ca2+ (0.8-160 microM) caused a concentration dependent increase in catecholamine secretion, which was characterized by a predominance of NA over Ad secretion. Acetylcholine (10-1,000 microM), high K+ (14-56 mM), and bradykinin (0.1-1,000 nM) all were confirmed to induce the release of more NA than Ad at all concentrations used. There was no apparent difference in the ratios of NA/Ad between Ca(2+)-induced catecholamine secretion from digitonin-permeabilized cells and those induced by secretagogues from cultured cells. Qualitatively the same result was obtained in the secretory responses to acetylcholine and high K+ in perfused adrenal glands. These results indicate that the effectiveness of Ca2+ for catecholamine secretion is higher in the secretory apparatus of NA cells than in that of Ad cells of the bovine adrenal medulla. This may be one of the reasons why the secretagogues cause a predominance of NA secretion over Ad secretion in the bovine adrenal medulla. PMID- 8473908 TI - The chronic administration of nicotine induces cytochrome P450 in rat brain. AB - The objective of these studies was to determine whether chronic administration of nicotine altered the cytochrome P450 (P450) monooxygenase system in rat brain. Male Sprague-Dawley rats received injections of nicotine bitartrate (1.76 mg/kg, s.c., twice daily for 10 days), and total cytochrome P450 content, the activity of NADPH-cytochrome c reductase, and the activities and relative abundance of P4502B1 and P4502B2 (P4502B1/2) were determined in microsomal fractions from rat brain. The content of P450 increased significantly (p < 0.02) in all brain regions examined from nicotine-injected rats; the largest increase (208% of control) was in frontal cortex and the smallest increase (122% of control) in cerebellum. The activity of NADPH-cytochrome c reductase was unaltered by nicotine administration. Benzyloxyresorufin O-dealkylase (BROD) and pentoxyresorufin O-dealkylase (PROD) activities, mediated by P4502B1/2, increased significantly (p < 0.02) following nicotine administration; the largest increase (213-227% of control) was in frontal cortex. Western blots of microsomal proteins indicated that the increase in enzymatic activity was associated with an increase in content of P4502B1/2 immunoreactive proteins. In contrast to brain, total P450 content, activities of NADPH-cytochrome c reductase, BROD, and PROD, and levels of P4502B1/2 immunoreactive proteins in liver were unaffected by chronic nicotine administration. Results indicate that chronic nicotine administration regulates the expression of P4502B1/2 in brain and that at the dose schedule used this effect occurs without a demonstrable effect on the hepatic P450 monooxygenase system. PMID- 8473909 TI - Angiotensin II type 1 receptor mRNA levels in the brains of normotensive and spontaneously hypertensive rats. AB - The type 1 angiotensin II (AII) receptor (AT1-R) has been implicated in the physiological actions mediated by AII in the brain. In view of the reported hyperactivity of the brain AII system in the spontaneously hypertensive rat (SHR), we compared the expression of AT1-R mRNAs in the brains of normotensive [Wistar Kyoto (WKY)] and SHR animals. Northern blot analysis showed about three- and approximately 20-fold increases in the levels of AT1-R mRNAs from the hypothalamus and brainstem areas, respectively, of the SHR compared with the WKY rat brain. This was attributable to greater levels of both AT1A- and AT1B-R mRNA subtypes in these areas from the SHR. These observations suggest that increased AII receptor levels in SHR brain may, in part, be a result of increased expression of the AT1-R gene. PMID- 8473910 TI - Identification of the cationic amino acid transporter (System y+) of the rat blood-brain barrier. AB - Cationic amino acids are transported from blood into brain by a saturable carrier at the blood-brain barrier (BBB). The transport properties of this carrier were examined in the rat using an in situ brain perfusion technique. Influx into brain via this system was found to be sodium independent and followed Michaelis-Menten kinetics with half-saturation constants (Km) of 50-100 microM and maximal transport rates of 22-26 nmol/min/g for L-lysine, L-arginine, and L-ornithine. The kinetic properties matched that of System y+, the sodium-independent cationic amino acid transporter, the cDNA for which has been cloned from the mouse. To determine if the cloned receptor is expressed at the BBB, we assayed RNA from rat cerebral microvessels and choroid plexus for the presence of the cloned transporter mRNA by RNase protection. The mRNA was present in both cerebral microvessels and choroid plexus and was enriched in microvessels 38-fold as compared with whole brain. The results indicate that System y+ is present at the BBB and that its mRNA is more densely expressed at cerebral microvessels than in whole brain. PMID- 8473911 TI - Age-dependent impairment of mitochondrial function in primate brain. AB - It has been hypothesized that some of the functional impairments associated with aging are the result of increasing oxidative damage to mitochondrial DNA that produces defects in oxidative phosphorylation. To test this hypothesis, we examined the enzymes that catalyze oxidative phosphorylation in crude mitochondrial preparations from frontoparietal cortex of 20 rhesus monkeys (5-34 years old). Samples were assayed for complex I, complex II-III, complex IV, complex V, and citrate synthase activities. When enzyme activities were corrected for citrate synthase activities (to account for variable degrees of mitochondrial enrichment), linear regression analysis demonstrated a significant negative correlation of the activities of complex I (p < 0.002) and complex IV (p < 0.03) with age but no significant change in complex II-III or complex V activities. Relative to animals 6.9 +/- 0.9 years old (n = 7), the citrate synthase-corrected activity of complex I was reduced by 17% in animals 22.5 +/- 0.9 years old (n = 6) (p < 0.05) and by 22% in animals 30.7 +/- 0.9 years old (n = 7) (p < 0.01). Similar age-related reductions in the activities of complexes I and IV were obtained when enzyme activities were corrected for complex II-III activity. These findings show an age-associated progressive impairment of mitochondrial complex I and complex IV activities in cerebral cortices of primates. PMID- 8473912 TI - The N-methyl-D-aspartate antagonist MK-801 fails to protect dopaminergic neurons from 1-methyl-4-phenylpyridinium toxicity in vitro. AB - Recent reports suggest that NMDA receptor antagonists when administered in vivo can protect dopaminergic neurons from the toxic actions of MPP+. In the present study the possible neuro-protective effects against MPP+ toxicity of the noncompetitive NMDA receptor antagonist MK-801 was studied in primary cultures of fetal rat mesencephalic dopamine neurons. MK-801 failed to protect dopaminergic neurons from MPP+ toxicity at concentrations that completely block NMDA-induced toxicity of these same neurons. In contrast to work carried out in cerebellar granule cells, MPP+ toxicity of mesencephalic dopamine neurons was unaffected by preexposure to subtoxic concentrations of either NMDA or cycloheximide. Our findings suggest that the toxic effects of MPP+ on dopaminergic neurons are not mediated through a direct interaction with the NMDA subtype of glutamate receptor. PMID- 8473913 TI - Neuromelanin and nigrostriatal dopamine neuron degeneration. PMID- 8473914 TI - Phospholipase D in chromaffin cells? PMID- 8473915 TI - Conformations of large cycloalkanes: cyclooctadecane, cyclononadecane and cycloicosane. AB - The conformations of cyclooctadecane, cyclononadecane, and cycloicosane were generated by a stochastic program that works in conjunction with MM2. The shapes of the rings are analyzed in terms of previous work by Dale and others, and in terms of distributions of energies, torsion angle distributions, and torsion angle sequences. A new shape element called the 'nick' has been discovered, and it seems to be increasingly important with 18-membered and larger rings. Previously suggested relationships between ring size and energy distribution were observed, and a geometrical explanation is provided for the relative distributions of stable conformations in 16-, 18-, and 20-membered rings. PMID- 8473916 TI - GenStar: a method for de novo drug design. AB - A novel method, which we call GenStar, has been developed to suggest chemically reasonable structures which fill the active sites of enzymes. The proposed molecules provide good steric contact with the enzyme and exist in low-energy conformations. These structures are composed entirely of sp3 carbons which are grown sequentially, but which can also branch or form rings. User-selected enzyme seed atoms may be used to determine the area in which structure generation begins. Alternatively, GenStar may begin with a predocked 'inhibitor core' from which atoms are grown. For each new atom generated by the program, several hundred candidate positions representing a range of reasonable bond lengths, bond angles, and torsion angles are considered. Each of these candidates is scored, based on a simple enzyme contact model. The selected position is chosen at random from among the highest scoring cases. Duplicate structures may be removed using a variety of criteria. The compounds may be energy minimized and displayed using standard modeling programs. Also, it is possible to analyze the collection of all structures created by GenStar and locate binding motifs for common fragments such as benzene and naphthylene. Tests of the method using HIV protease, FK506 binding protein (FKBP-12) and human carbonic anhydrase (HCA-II) demonstrated that structures similar to known potent inhibitors may be generated with GenStar. PMID- 8473917 TI - FOUNDATION: a program to retrieve all possible structures containing a user defined minimum number of matching query elements from three-dimensional databases. AB - A program is described that searches three-dimensional, structural databases, given a user-defined query, in order to retrieve all structures that contain any combination of a user-specified minimum number of matching elements. Queries consist of three-dimensional coordinates of atoms and/or bonds. Numerous query constraints are described which allow the investigator to define the chemical nature of the desired structures as well as the environment within which these structures must reside. They include: (1) Bonded vs. isolated atom distinction; (2) Atom type designation; (3) Definition of subsets with occupancy specification (>, =, < X atoms); (4) RMS-fit; (5) Active site volume accessibility of atoms linking query elements; (6) Number, atom type, and cyclic structure constraints for atoms linking pharmacophoric elements; (7) Automatic error boundary adjustment--ad infinitum constraint. To illustrate the capabilities of this program, queries based on the crystal structure of a thermolysin-inhibitor complex were tested against a subset of the Cambridge Crystallographic Database. Several compounds were returned which satisfied various aspects of the query, including fitting within the active site. Combination of segments of compounds which satisfy partial queries should provide a method for generating unique compounds with affinity for sites of known three-dimensional structure. PMID- 8473918 TI - Chiral chromatography and multivariate quantitative structure-property relationships of benzimidazole sulphoxides. AB - Various benzimidazole sulphoxides were chirally resolved employing an amylase based chiral stationary phase. The structure-property relationships of these compounds were investigated using calculated physicochemical properties, molecular modelling and multivariate statistical techniques. A data set of 254 molecular descriptors was used to represent the series of compounds. Analysis of the data set using principal components analysis and non-linear mapping suggested that the separation factor of each enantiomeric pair was associated with nine molecular properties and, in particular, molar refractivity of the Z substituent and the partial charge of atom 6. The separation factor of a sulphoxide not used in the analysis was well predicted thus suggesting that these models may be used to generalize. PMID- 8473919 TI - Nonlinear dependence in comparative molecular field analysis. AB - The applicability of the comparative molecular field analysis (CoMFA) approach to describe the nonlinear dependence of biological activity on lipophilicity in 3D quantitative structure-activity relationships (QSAR) has been demonstrated. The results indicate that the CoMFA approach is appropriate for describing nonlinear effects in 3D QSAR studies. PMID- 8473920 TI - Society of Nuclear Medicine. Proceedings of the 40th annual meeting. Toronto, Canada, June 8-11, 1993. Abstracts. PMID- 8473921 TI - The chief nurse officer as a board member: an overview. PMID- 8473922 TI - Nurse extenders. PMID- 8473923 TI - Delegation and the dilemma of the democratic ideal. PMID- 8473924 TI - An ethical nursing practice model. AB - Providing a framework within which nurses may practice is a challenge for nursing executives. The national emphasis on ethical issues and decision making provides a compelling argument for incorporating such concepts into practice models. The author discusses a nursing practice model based on five ethical principles that are applied to all aspects of nursing practice. PMID- 8473925 TI - Pediatric hotline. Meeting community needs while conserving healthcare dollars. AB - Faced with the challenge of providing cost effective services, administrators at the Hospital for Sick Children in Toronto, Canada recognized an opportunity to reduce unnecessary emergency visits. A telephone hotline was established to provide parents with reassurance and treatment guidelines that allowed them to care for their children at home. PMID- 8473926 TI - Incorporating nursing assistive personnel into a nursing professional practice model. AB - A pilot project evaluated the effect of incorporating nursing assistive personnel (NAP) into the existing nursing professional practice model at a tertiary care university medical center. A plan to use permanent, unit-based NAP was developed, implemented, and evaluated. Among the findings were a redistribution of selected nursing activities and conditions enhancing the integration of NAP to fulfill nonprofessional tasks and thus support the work of the registered nurse. PMID- 8473927 TI - Retaining registered nurses in rural community hospitals. AB - In rural practice settings where the task of recruiting new employees is exceedingly difficult, the first step in surviving the nursing shortage should begin with maintaining existing resources. Based on a survey of 2,488 staff registered nurses working in rural community hospitals, the authors compare personal, demographic, and practice characteristics of nurses by their self reported intentions to stay in their present positions. Specific areas of job dissatisfaction that best distinguish those who anticipate leaving in 1 year from those committed to remaining in their present job for 5 years or more are identified. PMID- 8473928 TI - The Albrecht nursing model for home healthcare: predictors of health status outcomes in working adults. AB - The health profile of American adults is heavily influenced by lifestyle behaviors. Therefore, working adults have a unique opportunity to take personal action to decrease their risk of cancer, heart disease, and other chronic illnesses and to improve their health status outcomes. Health status outcomes of working adults were evaluated through this quantitative study. Four structural variables (demographics, psychologic status, social status, and economic status), two modifying variables (access and cost), and three process variables (preventive care, including exercise/nutrition/stress management; client involvement; and family involvement) were examined as to their relationship to health status outcomes (client perception of health, amount of exercise, body mass index, and percent body fat). Results support the importance of the variables in the Albrecht nursing model in explaining health status outcomes in working adults. These factors may therefore be suitable targets for interventions to encourage healthy lifestyle behaviors at home. Nursing administrators, occupational health nurses, and home health nurses can use these findings to guide effective planning for wellness programs in the home and work setting. PMID- 8473930 TI - Child care problems of nurses. PMID- 8473929 TI - Decreased rehospitalization costs through intermittent nursing visits to nursing home patients. AB - This study determined if visits by a nurse to patients in contract nursing homes would reduce the cost of patient returns to the discharging medical center. The authors discuss an approach that reduced readmissions and emergency room visits, producing a net savings of $70,394.90. PMID- 8473931 TI - Computer simulations of the differentiated pay structure model. AB - The differentiated pay structure (DPS) model determines a nurse's base pay on the basis of education, position, and expertise level, adjusting that base for part time employment, differentials for nonbusiness hours, and single payment bonuses to reward longevity. Using computer simulations, the model was tested with data from two urban hospitals. The findings show that the model can be applied in a manner that is acceptable in terms of budget. By using the DPS model, administration can compensate for those objective employee behaviors that employers value the most. PMID- 8473932 TI - Is there a difference between an RN and an LPN? PMID- 8473933 TI - Patient-focused care service models and nursing: perils and possibilities. PMID- 8473934 TI - Ethics survey results. PMID- 8473935 TI - Work sampling and professional nurses. PMID- 8473936 TI - Successful implementation of computer systems: a planned organizational change approach. PMID- 8473937 TI - Increasing managers' visibility. PMID- 8473938 TI - Merit raises: are we paying for performance? PMID- 8473939 TI - Determinants of hospital length of stay. AB - An example of the inefficiency of cost-based reimbursement is that wide variations were observed between hospitals and between regions in the cost of treating similar diagnoses, with no apparent differences in quality. To correct these variations, the Tax Equity and Fiscal Responsibility Act and its concomitant prospective payment system based on DRGs was implemented. However, wide variations continued to exist among hospitals and regions in the United States. The attempt by the medical profession to refine the prospective payment system by severity adjustments has received lukewarm support. The work by Halloran et al on the relationship between nursing diagnosis and length of stay shows some promise. Studies on nursing intensity have produced mixed results. Recently, the Prospective Payment Assessment Commission decided to discontinue efforts to develop nursing intensity adjustments for DRG weights. Additionally, institutional characteristics, except for discharge planning programs, and patient characteristics have exhibited mixed results in attempts to explain hospital length of stay. Concern over continuing variations that DRGs and their proposed adjustments have been unable to correct led to the formation of the Agency for Healthcare Policy and Research, which was brought about by the Omnibus Budget Reconciliation Act of 1989. This agency seems to believe that practice patterns offer the greatest hope of reducing excessive hospital lengths of stay and concomitant costs. PMID- 8473940 TI - Building on the past to challenge the future. AB - The Council on Graduate Education for Administration in Nursing (CGEAN) was established to further the development and improvement of graduate education for administration in nursing. The Council seeks to identify the nature and direction of education for administration in nursing in various healthcare systems, providing guidelines for programs offering administration. A major goal of CGEAN is facilitating dialogue between nursing service administrators and graduate level educators who are engaged in teaching and research related to administration in nursing. This column, sponsored by members of the Council, will analyze and respond to position statements and trends related to the delivery of health services and graduate education for administrators in nursing. PMID- 8473941 TI - Designing for the future. AB - The American Organization of Nurse Executives (AONE) is the national organization of nurse executives and nurse managers. AONE provides leadership, professional development, advocacy, and research to advance nursing practice and patient care, promote nursing leadership excellence, and shape healthcare public policy. This column, written by officers and executive staff members of AONE, raises issues and discusses trends of importance to nursing administrators. PMID- 8473942 TI - Nursing department strategy, planning, and performance in rural hospitals. AB - Do strategic planning and nursing department strategies explain major differences in hospital performance? Answers to this question surfaced in a study of nursing directors of rural New Mexico hospitals. The results indicate that managerial strategies, cost-control strategies, and strategic planning by the nursing department explain differences in net income and operating margin. These results imply that nursing directors can take an active role in influencing the strategic direction and fiscal achievements of rural hospitals. PMID- 8473943 TI - Collaborating to develop a community-based health service for rural homeless persons. AB - In the current healthcare environment, public health nursing administrators are called on to create and manage programs and services while reducing cost and improving access. Public health science provides a framework on which to base program planning and management. Using this approach, the authors describe the establishment of a health services center to meet an identified gap in service to homeless persons in a rural area. PMID- 8473944 TI - Facilitating innovation at the nursing unit level through cultural assessment, Part 1: How to keep management ideas from falling on deaf ears. AB - The early hopes and expectations of organizational culture often fail to materialize because the nature of organizational culture is not understood. This article describes what culture is, explains where culture comes from, and analyzes the variety of subcultures that can exist in healthcare organizations. In so doing it explores why managerial ideas for change are not automatically implemented by organizational members. The importance of assessing a group's culture before implementing change is discussed. Tools for assessing the work group culture of a nursing unit are presented. Part 2 (May 1993) will describe a five-step process to strengthen the forces that drive cultural change and overcome forces that resist innovation. PMID- 8473945 TI - The organizational culture. Implications for nursing service. AB - Research has established positive links between a constructive culture, the morale and retention of employees, and the decreased mortality of patients. Given these important variables and their ties to organizational culture, it is important to understand the culture of nursing service. Even more important are the implications that the culture provides for development of strategies to enhance the service. For these reasons, this study assessed the organizational culture of seven acute care hospitals to provide a background for discussion of the implications and strategies to enhance service. PMID- 8473946 TI - Development and evaluation of a research-based management intervention. A recognition protocol. AB - Recognition of work has been positively related to job satisfaction and retention of nurses in the research literature. The authors describe the development of a research-based management intervention to provide recognition, implementation of the intervention by head nurses, and the evaluation of the outcomes. PMID- 8473947 TI - Simultaneous discrimination of the spatial frequency and contrast of periodic stimuli. AB - Discrimination thresholds for spatial frequency and contrast were measured as a function of (1) the spatial-frequency bandwidth of the stimuli, (2) the reference contrast of the stimuli, and (3) whether the observer knew on which dimension, spatial frequency or contrast, the stimuli would differ. Relative bandwidth was manipulated by a one-dimensional Gaussian window and varied from 0.25 to 2.0 octaves. The results of two different tasks were compared. In a single-judgment task the observer knew on which dimension the stimuli would differ, and discrimination thresholds were measured in a standard two-interval forced-choice staircase procedure. In a dual-judgment task the dimension on which the stimuli differed varied from trial to trial. In this task the observer made two judgments on each trial in a modified two-interval forced-choice procedure: (1) on which dimension the stimuli differed and (2) in which interval the stimulus with the higher spatial frequency or contrast appeared. Thresholds were measured by five interleaved staircases for five reference contrast levels that varied from 0.02 to 0.32. Thresholds for both spatial frequency and contrast increased with increasing stimulus bandwidth and decreased with increasing stimulus contrast. Thresholds were, on average, 1.8 times higher in the dual-judgment task than in the single-judgment task, independent of the stimulus contrast and the bandwidth. A stimulus-uncertainty model is described that accounts for the difference between thresholds in the single- and the dual-judgment tasks. PMID- 8473948 TI - [Studies on otolaryngeal Chlamydia trachomatis infection province (a case report and seroepidemiological study)]. AB - Recently, chlamydial infection patterns have undergone considerable change. Chlamydia trachomatis has, in particular, been described as a major cause of sexually transmitted diseases. Because of the more liberal attitude concerning sexual life-styles and behavior patterns, the oral cavity and pharynx has been increasingly becoming a site of infection for many sexually transmitted diseases. In the otolaryngeal region, because of oro-genital sexual relations, C. trachomatis infection is presently attracting a great deal of attention. The authors report a case of pharyngitis and cervical lymphadenitis due to C. trachomatis infection contracted from oral sexual activity. Initially, this was suspected to be a case of malignant lymphoma, but histological studies in biopsy specimens of the epipharynx and cervical lymph nodes revealed no malignant cells. Serum antibody titers against mycoplasma and a number of viruses were not elevated while those against C. trachomatis were, based on results of the microplate immunofluorescence antibody technique. C. trachomatis antigen was demonstrated in pharyngeal scrapings by an isolation method and direct immunofluorescence test. In addition, inclusion bodies of C. trachomatis were demonstrated in biopsy specimens from the lateral funiculus of the pharynx by direct immunofluorescence test using a MicroTrak. The authors studied the seroepidemiology of chlamydial infection in healthy controls, patients with acute respiratory infection and patients with inflammation or infection in the otolaryngeal region. Among adult patients with otolaryngeal inflammation, the carrier rate for C. trachomatis specific antibodies was higher than in other groups. In females, especially, the carrier rate for C. trachomatis specific antibodies was very high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473949 TI - [Relationship between cervical osteophytes and globus sensation--a study based on altered swallowing function]. AB - The swallowing function of ten patients showing marked cervical osteophytes were studied by double contrast pharyngogram and manometric examinations. In five cases in which the pharyngeal clearance was B type according to Shuzaki's classification, a significant increase in the maximal swallowing pressure value on the oral side ipsilateral to the osteophytes was often observed. In five cases in which the pharyngeal clearance showed A + A' type (marked impairment), the frequency of significantly decreased maximal swallowing pressure on the oral side ipsilateral to the osteophytes and abnormal waveforms of the swallowing pressure were high. However, no definite correlation was noted between these changes in swallowing function and osteophyte site. Therefore, there are two possible outcomes of the changes in swallowing function caused by cervical osteophytes: one is a compensatory increase in pharyngeal constriction aimed at maintaining relatively good pharyngeal clearance, the other is impaired pharyngeal constriction and the pharyngeal clearance. These changes in swallowing function would impact on globus sensation. PMID- 8473950 TI - [Case report of a foreign body in the nasal cavity: experimental research on limited damage]. AB - We report here a case of serious nasal cavity tissue damage caused by a foreign substance, specifically, a button-shaped battery. The patient was a three-year old boy who inserted a button-shaped battery into his left nasal cavity. On examination, we found necrosis of the nasal mucosa, cartilage and bone. In addition, the nasal cavity structure was severely damaged. In a follow-up experiment, we inserted a similar button-shaped battery, pre-soaked in a salt solution, into a rabbit's nasal cavity and measured daily changes in PH and discharge over time. In addition, we assessed how much nasal cavity tissue was damaged in a pathological specimen. We found that the chief factor mediating tissue damage, among those we tried, was strong base production with low voltage discharge. Under these conditions the nasal cavity is damaged in a short time. PMID- 8473951 TI - [Cochlear immune injury following direct antigen challenge to the endolymphatic sac]. AB - Following direct KLH antigen challenge to the endolymphatic sac (e. sac) in guinea pigs, degeneration of the cochlea was examined histologically by light microscopy. Degeneration was seen in 21 out of 140 animals presensitized systemically from day 1 to 5 weeks post secondary KLH challenge to the e. sac. Degeneration of the organ of Corti, stria vascularis and spiral ganglion cells was seen from day 1 in 19, 17 and 7 animals, respectively. There was no increase in these degenerative processes during the time course. In the period from day 1 to day 4, severe bleeding in the perilymphatic space occurred simultaneously with cochlear deterioration. Three animals showed perilymphatic fibrosis which was noted after the first week post KLH secondary challenge. In contrast, animals primarily challenged with KLH (locally administered to the e. sac) showed no cochlear degeneration. These results suggest that a locally mounted immune response in the e. sac can cause direct immune injury to cochlear tissues. PMID- 8473952 TI - [The localization and the function of carbonic anhydrase in the inner ear]. AB - Carbonic anhydrase (CA) is distributed in a wide variety of animal cells and tissues, especially in cells and tissues involved in rapid exchange or transport of protons, bicarbonate, or other ions. Although localization of this enzyme and its physiological roles in the inner ear have been investigated extensively, full clarification has yet to be achieved. We have conducted a histochemical investigation of CA localization in the inner ear of the guinea pig by Hansson's method, with emphasis on improved fixation. The histochemical reaction for CA activity is localized in the outer and inner hair cells of the organ of Corti, Deiters' cells or nerve endings, inner pillar cells, Boettcher's cells, stria vascularis, spiral ligament, vasculo-epithelial zone and spiral ganglion cells. The physiological roles of CA in the inner ear, particularly in relation to the production or absorption of endolymph, are discussed in this report. PMID- 8473953 TI - [Clinical study of children with nasal allergy]. AB - Possible factors influencing nasal allergy in children were studied using a questionnaire and allergic examination including eosinophil count of nasal discharge, IgE RAST score to house dust and provocation test. We investigated three groups of children according to the results of allergic examinations. The negative group, the equivocal group and the definite group, respectively, consisted of 40, 49 and 107 children. We found the prediction value of definite group with eosinophil count of nasal discharge, IgE-RAST score and provocation test to house dust were respectively 77.0, 89.2 and 78.1%. Bottle feeding and history of asthma bronchiale occurred more frequently in the definite group. These observations provide epidemiologic and clinical bases for further investigations of children with nasal allergy. PMID- 8473954 TI - [A case of superficial siderosis of the central nervous system with total deafness]. AB - Superficial siderosis of the central nervous system (SSCN) in a disease characterized by chronic deposition of hemosiderin in the leptomeninges, subpial tissue, spinal cord, and cranial nerves. Previously the diagnosis of SSCN could only be made at autopsy or during a neurosurgical procedure. Now, however, a diagnosis of SSCN can be made non-invasively by magnetic resonance imaging (MRI). We present the case of a 50-year-old male with SSCN accompanied by bilateral sensorineural hearing loss which gradually progressed to total deafness over a seven year period. This patient also had associated bilateral caloric weakness with episodes of severe recurrent headaches over the two preceding years. The deafness and gait disturbance, which were his chief complaints, were followed by other neurological manifestations including pyramidal tract signs, anosmia, and ageusia. High-field MRI on T-2 weighted images of the CNS showed diffuse marginal hypointensity of the cerebrum, brain stem, and cerebellum. Atrophy of the cerebellum and brain stem was also apparent. Low signal intensity along the proximal segment of the acoustic nerve and the facial nerve was noted from the cistern to the internal auditory canal. Neither bilateral transtympanic promontory nor round window electrical stimulation elicited any sound sensation. In this case it was thought that the acoustic nerve alone or both the acoustic nerve and the cochlea were affected by this disease. Consequently, cochlear implantation was not indicated. The source of bleeding into the subarachnoid space could not be detected despite thorough examination. This diagnosis will be made only by physicians who are aware of this rare entity and have knowledge of the characteristic clinical pathology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473955 TI - [Psycho-physiological study by contingent negative variation (CNV) in otolaryngological diseases]. AB - Contingent negative variations (CNV) were recorded in patients with tinnitus (N = 20), abnormal sensations of the pharynx and larynx (ASPL) (N = 26) and Meniere's disease (N = 19), and compared with those of healthy adults (N = 20) in order to investigate the characteristics of their information processing mechanisms in the brain. Patients were also subjected to psychological tests: Depression Score and the Cornell Medical Index test. CNV (an event-related potential) is a slow negative cortical potential shift and can be recorded during two stimuli presented at a constant interval under conditions in which the subjects are told to press a key as quickly as possible upon an imperative stimulus (S2) following a warning stimulus (S1). S1 was a 1kHz tone burst of 300 msec duration at a level of 85dB HL. S2 was a light flash. The interstimulus (S1-S2) interval was set at 2 seconds. The CNV can be divided into three components, early, middle, and late, according to latency. Statistical analysis of CNV amplitudes of the three components showed the following differences between groups. In tinnitus patients, the mean amplitudes of both the early and middle component were significantly greater than those in healthy adults (P < 0.05). In ASPL patients, the mean amplitudes of the middle component were significantly greater than those in healthy adults (P < 0.05). In Meniere's disease, the mean amplitudes of both the middle and late component were significantly greater than those in healthy adults (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473956 TI - [Autonomic nervous function of vertiginous patients--assessment by spectral analysis of heart rate variability]. AB - Autonomic nervous function in 68 vertiginous patients and 33 controls was studied using power spectral analysis of heart rate variability. First, a system was developed which computes the power spectral density (PSD) of beat-to-beat heart intervals using a continuous non-invasive finger blood pressure recording obtained with the FINAPRESS device. A fast-Fourier transform algorithm was used to compute the PSD. In frequencies up to 0.5 Hz, the PSD of heart rate variability contains three major components: a low frequency (P1), a middle frequency (P2) and a high frequency (P3). Each component was normalized by dividing the absolute values by total power (T), and then used as an index of each component. Second, the effects of passive tilt, respiratory frequency and specific pharmacological sympathetic or parasympathetic blockade on the indices of these components were evaluated in the control group. The following results were obtained. 1. During passive tilt, the normalized power of P2 was increased, whereas that of P3 was decreased. 2. The peak frequency of P3 was consistent with the frequency of respiration. 3. Sympathetic blockade decreased the normalized power of P2, whereas parasympathetic blockade decreased the normalized power of P3. From these results, I concluded that the normalized power of P2 and P3 are quantitative markers of sympathetic and vagal nervous activities, respectively. Third, the results of spectral analysis in patients were compared with those in controls. The following characteristics of autonomic nervous function in vertiginous patients were noted. 1. The normalized power of P3 in patients was lower than that in controls, suggesting that parasympathetic nervous activity at rest was suppressed in patients. 2. The increase of normalized power of P2 with passive tilt was suppressed in patients, suggesting suppression of sympathetic response to passive tilt. 3. In patients with Meniere's disease, during the active period of vertigo attacks, the normalized power of P2, which is an index of sympathetic activity, was higher than that in the intervals between vertigo attacks. Fourth, with caloric stimulation in the control group, an increase of the normalized power of P2 was observed during or after the stimulation, which suggests that vestibular stimulation increases sympathetic activity. I therefore suggest the following: 1. Decreased parasympathetic activity and suppression of sympathetic response were present in the vertiginous patients. 2. Sympathetic activity was increased by vertigo attacks in the patients with Meniere's disease. PMID- 8473957 TI - [Studies on the morphology and strength of the tympanic membrane after experimental myringotomy]. AB - The tympanic membrane is a biomembrane made of thin vibrant material. The tension and strength of the tympanic membrane rely mainly on the radial fibers in the lamina propria. Experimental myringotomy by linear incisions were made at right angles to the radial fiber bundles in the tympanic membrane of 54 guinea pigs. The healing process was observed chronologically by light, polarized light and electron microscopy for two years. The mechanical strength of recovery of the tympanic membranes were then studied using a microtension tester developed by our laboratory. The tensile direction was parallel to the radial fiber bundles of the tympanic membrane, and the tensile rate was 1 x 10(-3) m/sec. 1. Light microscopic observation showed that the radial fiber bundles did not reconstruct continuously even after two years. Polarized light microscopic observation showed that parts of the linear incision of the tympanic membrane contained polarized fibers in place of the normal radial fibers. Transmission electron microscopic observation of the tympanic membranes after four months showed that the radial fibers were cut off sharply, but that the lamina propria had regenerated with different fibers. Several fibroblasts were also observed. Scanning electron microscopic observation through the auditory canal after two years showed that thick masses of scar adhered to the site of the experimental incision of the tympanic membrane. This scar was composed of several layers of collagen fibers. The area of scar adhesion was also observed on the membrane facing the tympanic cavity, but it was thinner than the scars on the meatal side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473958 TI - [Practical hearing compensation and an assessment of hearing effect in patients with profound hearing loss using hearing aids]. AB - This investigation was carried out to study practical hearing compensation with hearing aids and the correlation between subjective evaluation (questionnaire survey) and objective evaluation (speech perception test) as an assessment of hearing aid effect in patients with profound hearing loss. 1. Forty-nine patients with hearing levels of 90dB or more (23 men and 26 women) were examined. Their mean and median hearing levels were 105.9dB (standard deviation: 10.4dB) and 106.3dB, respectively. The patients ranged in age from 18 to 74, with a mean age of 47.4. 2. Subjective evaluation was carried out by a questionnaire survey in which the patients chose one of 4 or 5 graded categories in 10 different hearing conditions, and three items of "satisfactory", "uneasiness" and "effectiveness". Speech sound discrimination ability for vowels and monosyllables, and speech intelligibility of words and sentences, were evaluated in audition only (A), vision only (V) and a combination of both (A + V), totaling 12 conditions with hearing aids as the objective evaluation using video tapes materials. 3. The subjective evaluation revealed that 60% of patients with hearing loss of 90-110dB understood "one to one conversation in a quiet place". Speech perception was poorer in "conversation in a noisy place" than in "conversation in a quiet place". Speech perception became poorer in the order of "one to one", "to a few people", and "to many people". For subjective feeling, 56.4% answered "satisfactory", and for hearing aid effectiveness, 78.7% answered "effective". 4. In the objective evaluation, the rates of correct answers were 19.6% in A and 46.3% in A + V for monosyllables, 19.8% in A and 43.4% in A + V for words, and 29.5% in A and 60.0% in A+V for sentences. 5. There were significant correlations (p < 0.001) between subjective evaluation of "in a quiet place and one to one conversation" (among other conditions) and objective evaluations of monosyllables, and word and sentence recognition, mostly in A and A + V. These results suggest that hearing compensation by hearing aids can be evaluated objectively in patients with profound hearing loss when word and sentence recognition tests are performed in addition to the monosyllable recognition test, and it is more practical if vision is examined in addition to hearing for speech perception in patients with profound hearing loss. PMID- 8473959 TI - [Immunohistochemical study of proteoglycans and collagens in the mouse cochlear duct]. AB - Immunohistochemical studies of proteoglycans and collagens (type I and type IV) in the cochlear duct, and of the effects of cisplatin (CDDP), were performed. In cells of the organ of Corti and in the middle layer of the stria vascularis, heparan sulfate proteoglycan (HSPG) and collagens (type I and IV) or collagen like substances were found. HSPG in these locations appeared to play important roles in the production of auditory sense. The tectorial membrane contained HSPG and collagens (type I and IV). However, no data supporting the concept that elements of the tectorial membrane are derived from interdental cells was obtained. In the basilar membrane, no HSPG, chondroitin sulfate (Chs), or collagens (type I and IV) were detected. The unique structures containing these substances reacted strongly with anti-HS (heparan sulfate), anti-HSPG-CP (core protein) and anti-collagen (type I and IV) antibodies that developed in the middle layer of the stria vascularis after the administration of CDDP. However, no change was observed in the tectorial membrane, the spiral prominence, the basilar membrane, or the spiral limbus. The decrease in HSPG in cells of the organ of Corti, and the changes in the stria vascularis, may help solve the well known contradiction between the severity of morphological damage and of the hardness of hearing. PMID- 8473960 TI - [Clinical anatomy of the trachea and esophagus]. PMID- 8473961 TI - Feigning schizophrenic disorders on the MMPI-2: detection of coached simulators. AB - The Minnesota Multiphasic Personality Inventory (MMPI) and, more recently, its revised version (the MMPI-2) have represented the "gold standard" in the psychometric assessment of malingering and other response styles. In this study, we provide a stringent test of the MMPI-2 validity indices and their ability to detect feigned schizophrenia in four groups of simulators (n = 72). Simulators were randomly assigned to one of four conditions: (a) coached on symptoms of schizophrenia, (b) coached on strategies for the detection of fakers, (c) coached on both symptoms and strategies, or (d) uncoached. Simulators were compared to subjects responding under an honest condition (n = 13) and a comparison group of schizophrenic inpatients (n = 37). We found knowledge of strategies alone allowed many simulators (i.e., one third or more, depending on the validity indices) to elude detection. In contrast, knowledge of the disorder appeared less useful to simulators in avoiding detection. Coaching on both strategies and symptoms was not as effective as strategies alone. Consistent with previous studies, uncoached simulators were detected with moderately high levels of accuracy. PMID- 8473962 TI - Use of the MMPI to assess the construct validity of the revised Social Anhedonia Scale as an index of schizotypy. AB - We evaluated the construct validity of the revised Social Anhedonia Scale (SAS; Mishlove & Chapman, 1985) through an examination of the Minnesota Multiphasic Personality Inventory (MMPI) profiles produced by extreme scorers on the SAS. The MMPI classification strategy employed by Moldin, Gottesman, and Erlenmeyer Kimling (1987) was used to group profiles with regard to their specificity to schizophrenia spectrum disorders. Of 1,124 college students, 58 females and 60 males had elevated SAS scores. Thirty-five percent of the males and 24.14% of the females produced MMPI profiles within the Moldin et al. classification scheme. Another 27.59% of females and 23.33% of males had profiles that are sometimes associated with schizotypal attributes. Thus, 41.67% of high-SAS males and 48.28% of high-SAS females have MMPI profiles that are unlikely to be associated with a heightened risk for schizophrenia. Because only a subset of socially anhedonic subjects produced schizophrenia spectrum MMPI profiles, it appears that the SAS, in isolation, should not be used to identify individuals at risk for schizophrenia. The revised SAS, like its predecessor, does not appear uniquely related to the schizophrenia spectrum. Unlike Mishlove and Chapman (1985), we did not find a gender difference among subjects. PMID- 8473963 TI - The MMPI and the MCMI in the evaluation of narcissism in a clinical sample. AB - Narcissistic and nonnarcissistic groups of psychiatric patients (n = 35 in each group) were formed on the basis of a criterion comprised of clinical judgment and scores on the Narcissistic Personality Inventory and compared on the Minnesota Multiphasic Personality Inventory (MMPI) and the Millon Clinical Multiaxial Inventory (MCMI) profiles and on six special narcissism scales. Significant profile differences between narcissists and nonnarcissists were obtained on the MMPI and MCMI. Four of the six narcissism scales produced significant differences between the two groups. PMID- 8473964 TI - The psychometric assessment of alcoholism in forensic groups: the MacAndrew scale and response bias. AB - Although the MacAndrew Alcoholism scale is the most widely used Minnesota Multiphasic Personality Inventory (MMPI) measure of vulnerability to alcohol abuse, its accuracy has not been studied in patients intrinsically motivated to exaggerate or minimize psychopathology. We examined the usefulness of the MAC in predicting alcohol abuse in a forensic clinical sample. Results indicate the MAC (a) was not more effective than direct inquiry in this group, (b) scores were correlated negatively with minimization and positively with exaggeration for subjects with histories of alcohol abuse, (c) offered advantages over direct inquiry both in screening for alcohol history (sensitivity) and in confirming it (specificity), and (d) scores were only moderately more accurate in valid than in minimized or exaggerated MMPI protocols. The results suggest that clinicians should use the MAC cautiously, particularly when they suspect motivation to minimize psychopathology. PMID- 8473965 TI - A profile of personality for a Russian sample: as indicated by the Comrey Personality Scales. AB - The purpose of our study was to present a personality profile, based on data from the Comrey Personality Scales (CPS), for a diverse, Russian sample. The CPS was administered to 457 subjects drawn from convenience samples throughout St. Petersburg, Russia. In Part 1 of the study, the structure of the Russian sample's personality was identified. Data from the CPS were factor analyzed. Findings showed strong support for the generalizability of Comrey's (1970) eight-factor personality taxonomy to this sample. The CPS's factors derived from the Russians were compared and found to be similar in structure to samples derived from American, Australian, Brazilian, Israeli, Italian, and New Zealand samples. In Part 2, mean differences on the CPS's scales between the Russian sample and the American sample were assessed. Results showed that although the structure of the Russians' personality was similar to that of the Americans' personality, significant differences in the elevation of scale scores did exist. For example, as a whole, the Russians tended to be more defensive, lethargic, egocentric, and unstable. Contrary to popular expectations, however, the Russians were not more conforming. PMID- 8473966 TI - Discriminant validity of the Inventory to Diagnose Depression. AB - Measures of depression and anxiety correlate highly with one another. It has been hypothesized that this shared variance partly reflects poor discriminant validity, which could be improved by linking item content more closely to diagnostic criteria. We tested this speculation by comparing the Inventory to Diagnose Depression (Zimmerman, Coryell, Corenthal, & Wilson, 1986), developed to correspond with diagnostic criteria for major depression, with the Beck Depression Inventory (Beck, Rush, Shaw, & Emery, 1979) in terms of discriminant validity. These measures correlated more strongly with each other than with anxiety but did not differ in their relations with anxiety. PMID- 8473967 TI - Bipolarity in Jungian type theory and the Myers-Briggs Type Indicator. AB - The standard form of the Myers-Briggs Type Indicator (MBTI; Myers & McCaulley, 1985) was constructed to measure introversion/extroversion, sensing/intuiting, and thinking/feeling as single, bipolar dimensions. We tested this assumption of bipolarity with a Likert form of the MBTI that allowed for the independent assessment of each attitude and function. A total of 106 female and 59 male undergraduate and graduate students completed the standard and Likert MBTI forms approximately 3 weeks apart. Evidence for the bipolarity of the introversion/extroversion dimension was weak, and findings did not support the bipolarity of the sensing/intuiting or thinking/feeling dimensions. Results provide evidence that high negative correlations within MBTI dimensions are an artifact of its forced-choice format. Implications of the findings for typology measurement are discussed. PMID- 8473968 TI - The factor structure of the Rorschach for adolescent inpatients. AB - The factor structure of the Rorschach inkblot test was examined using a sample of 268 adolescent inpatients (including 105 with conduct disorders and 105 with depressive disorders). An initial analysis found a four-factor solution for both the conduct-disordered and depressive-disordered groups. However, examination of the factor patterns suggested that these groups did not yield significantly different factor structures. Thus, for the final analysis all inpatients were combined, and a single three-factor solution was found. These factors were substantively similar to the initial analysis and were interpreted as consisting of (a) struggles with affective expression, (b) general psychological health, and (c) perceptual organization. PMID- 8473969 TI - The use of the Rorschach to differentiate unipolar and bipolar disorders. AB - We compared the Rorschach performance (using the Comprehensive System; Exner, 1986) of 29 unipolar depressed, 15 bipolar depressed, and 18 bipolar manic inpatient subjects (N = 62) classified on the basis of the Research Diagnostic Criteria (RDC; Spitzer, Endicott, & Robbins, 1985). The three main groups differed from one another on a variety of variables, especially those related to ideation and information processing. One finding of particular importance was that bipolar depressed subjects, like bipolar manic and unlike unipolar depressed subjects, showed a high level of cognitive slippage. These results suggest that the Rorschach possesses utility in the differential diagnosis of affective disorders. PMID- 8473970 TI - A Rorschach study of narcissism, defense, and aggression in borderline, narcissistic, and cluster C personality disorders. AB - We examined the differences between narcissism, mode of defense, and level of aggression on the Rorschach. We also investigated differences in borderline, narcissistic, and Cluster C personality disorders by examining responses to Rorschach content variables. The Lerner Defense Scale (P. Lerner & H. Lerner, 1980), the aggressive content section of the Holt (1977) method for assessing primary process manifestations, a modified version of Exner's (1986a) Egocentricity Index, Wagner's (1965) exhibitionistic M score, and grandiosity were scored on the Rorschach protocols of 17 borderline, 17 narcissistic, and 17 Cluster C personality disorders. Borderlines were found to employ primitive defensive structures to a greater degree and severity, show more intense and overall aggression as well as more responses on the three forms of aggression in the Holt method, and have higher levels of grandiosity. Narcissists evinced significantly higher levels of egocentricity than borderlines and higher levels of idealization than the Cluster C group. Convergent validity was found on the measures of defense and aggression, which showed a strong relationship between primitive aggression and primitive defense. PMID- 8473971 TI - Validity of the Children's Picture-Frustration Study: a social-cognitive perspective. AB - We used three studies to examine the validity of hostility scores from the Children's Form of the Picture-Frustration (P-F) Study in the context of Dodge's (1986) social information-processing model of aggression. Dodge's theory states that frustration results in retaliatory aggression only if the frustrated individual attributes hostile intent to the frustrator. Further, differences between aggressive and nonaggressive children in retaliatory aggression are more likely when the frustrator's intent is ambiguous than when the frustrator's intent is clear. In Study 1, items on the Children's P-F Study were rated by 237 children according to how mean they believed the frustrator in each item was. Results showed that items varied significantly in the amount of hostility portrayed. On the basis of these ratings, items were divided into those in which the intent was hostile, nonhostile, or ambiguous. In Studies 2 and 3, we tested Dodge's theory that differences between aggressive and nonaggressive children would be revealed on those items in which the frustrator's intention is ambiguous. In both studies, teacher's ratings of children's retaliatory aggression correlated significantly with the scale comprised of the ambiguous items but not with the scales comprised of the hostile or nonhostile items. The results provide further support to Dodge's theory of aggression and to the use of the Children's P-F Study within a social-cognitive perspective. PMID- 8473972 TI - Clinical correlates of MMPI depression scales. AB - We investigated whether Scale 2 (Depression [D]) and the Wiggins Content Scale of Depression (DEP) of the Minnesota Multiphasic Personality Inventory (MMPI) have different clinical correlates when only one of these two scales is elevated. According, a group of patients who elevated DEP higher than Scale 2 (DEP > 2) were compared with a group of patients who elevated Scale 2 higher than DEP (2 > DEP). The patients with DEP > 2 were rated as being less severe than the patients with 2 > DEP on the following Brief Psychiatric Rating Scales: Somatic Concern (SOM), Emotional Withdrawal (WDRA), Depressive Mood (DEP), and Blunted Affect (AFF). The patients with DEP > 2 were rated as more severe on Excitement (EXC). The patients with DEP > 2 were more likely to receive the Axis I diagnoses of: bipolar disorder, manic, and alcohol abuse. Schizophrenia was equally probable for patients in the two groups. It appears that these two MMPI scales of depression have different clinical correlates when either one scale or the other is elevated. PMID- 8473973 TI - Screening for maladjustment in college students: an application of receiver operating characteristic curve to MMPI scales. AB - The ability of two scales derived from the Minnesota Multiphasic Personality Inventory (MMPI) to identify emotional maladjustment in a college setting was examined. The scales were the College Maladjustment scale (Mt) developed by Kleinmuntz (1961) and the Health Opinion Survey based Emotional Disorder scale (Ed). Emotional maladjustment was defined by criteria established in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987) and assessed through a computerized Diagnostic Interview Schedule. Subjects were 94 female and 62 male students, 51 of whom (33%) met criteria for at least one DSM-III-R disorder. Substance use disorders were most frequent (13.5%), followed by anxiety disorders (11.5%) and depressive disorders (7.1%). Both Mt and Ed had no relationship to substance use disorders but were moderately related to nonsubstance use maladjustment (r approximately .47); receiver operating characteristic (ROC) analysis was employed, and Mt and Ed proved to be a fair-to-good indicator of nonsubstance use maladjustment. Types of decision errors are discussed, and tables provide information concerning predictive accuracy across the entire range of scores. PMID- 8473974 TI - Content overlap inflates the relation between negative cognition and dysphoria. AB - We investigated whether the presence of items assessing negative cognition on the Beck Depression Inventory (BDI) inflates the relation between BDI scores and measures of negative cognition. In four student samples, we examined the relation between measures of self-esteem, dysfunctional attitudes, control beliefs, perceived social support, and BDI scores calculated with and without negative cognition items. There were significant reductions in the strength of the relations between self-esteem, dysfunctional attitudes, and BDI scores when overlapping content was removed. Moreover, this was not due to the increase in error variance resulting from reducing the number of items on the BDI. Although the magnitude decreased, the relation between negative cognition and dysphoria remained significant in all comparisons even when overlapping content was removed. Thus, although content overlap appears to inflate the relation between some measures of negative cognition and dysphoria, it cannot completely account for their relation. PMID- 8473975 TI - How do individuals remember their past statements? AB - It was hypothesized that when it is difficult for people to remember what they said previously, they may use their sense of familiarity with a statement to determine whether it is one they expressed. In 3 experiments, Ss were asked to state whether they had witnessed certain objects in a previous slide presentation; they responded aloud with experimentally mandated statements. The familiarity of target statements was varied, independent of whether they were expressed, through extraneous presentations of the pertinent objects. Later, Ss tried to determine whether (Experiments 1 and 2), or how frequently (Experiment 3), they expressed the target statements. Results supported the hypothesis: Ss were more likely to remember making statements concerning the more familiar objects than the less familiar objects. PMID- 8473976 TI - Effect of temporal perspective on subjective confidence. AB - Four studies examined whether people tend to lose confidence in their prospects for success the closer they are to the "moment of truth." Study 1 found that students think they will do better on their midterm exams when asked on the 1st day of class than when asked on the day of the exam. Studies 2 and 4 replicated this finding under controlled conditions. Study 3 demonstrated that the same effect holds retrospectively: People are more confident that they would have performed well at a task long after the time to perform has passed. Data are presented indicating that these results stem from a tendency for people to feel more "accountable" for their assessments, and thus focus less on the causes of success and more on the causes of failure, as the time to perform approaches. Implications for the experience of regret are discussed. PMID- 8473977 TI - Effects of social support and conflict on adolescent children of alcoholic and nonalcoholic fathers. AB - Studies of positive and negative social ties usually are done in isolation of each other, precluding an understanding of their relative contributions to psychological functioning. This research evaluated the effects of adolescents' conflict with and social support from key relationships (parents, siblings, and best friends) on adolescents' self-esteem, substance use, and externalizing symptoms. Ss were 296 adolescents and their parents; 145 families had alcoholic fathers, and 151 had nonalcoholic parents. Support and conflict provided by each network member showed only a mild negative correlation. Support from parents, but not siblings or best friends, was related to adolescents' reports of substance use and externalizing. Conflict with parents was consistently related to externalizing behaviors. There was no evidence that conflict within a relationship neutralizes the effectiveness of the support it provides. PMID- 8473978 TI - Dysphoria and decision making: limited information use for evaluations of multiattribute targets. AB - The hypothesis was that dysphoric relative to nondysphoric individuals use less available, relevant information in decision making because of reduced attentional resources. Dysphoric and nondysphoric Ss evaluated 70 jobs, each of which was described in terms of 5 dimensions (e.g., friendliness of co-workers); there were 5 possible values for each dimension. In both studies, dysphoric relative to nondysphoric Ss used a smaller subset of information, yet did not simplify what information was used and did not combine the information in a more simple manner. The limited information use was not due to dysphoric Ss' systematically ignoring certain dimensions and was evident in both initial and final portions of the task. Dysphoric Ss spent as much time and reported using as much information and investing as much effort as nondysphoric Ss. Reported effort alone was related to actual information use. PMID- 8473979 TI - Gender-related traits and gender ideology: evidence for a multifactorial theory. AB - Male (n = 95) and female (n = 221) college students were given 2 measures of gender-related personality traits, the Bem Sex-Role Inventory (BSRI) and the Personal Attributes Questionnaire, and 3 measures of sex role attitudes. Correlations between the personality and the attitude measures were traced to responses to the pair of negatively correlated BSRI items, masculine and feminine, thus confirming a multifactorial approach to gender, as opposed to a unifactorial gender schema theory. PMID- 8473980 TI - Depression and the impression-formation continuum: piecemeal processing despite the availability of category information. AB - A study explored depressed-nondepressed differences in impression formation. From S. T. Fiske and S. L. Neuberg's (1990) model of impression formation, mildly depressed perceivers were hypothesized to engage in more piecemeal processing when forming an impression of a target other, even when nondepressed perceivers would typically use less effortful, categorical processing. With an idiographic technique designed by M. Pavelchak (1989), depressed Ss were shown to use trait attributes in evaluating a person, even when induced to categorize the individual. Nondepressed Ss relied on category information when available, replicating Pavelchak's study. Depressed Ss' results are interpreted as arising from a motivation to engage in effortful analysis of social information, stemming from feelings of lack of control over life events. PMID- 8473981 TI - Integrating bottom-up and top-down theories of subjective well-being: the case of health. AB - As a means of integrating bottom-up and top-down theories of subjective well being (SWB), a framework was proposed that, in part, posits that both objective life circumstances and global personality dimensions indirectly affect SWB through their effects on the interpretation of life circumstances. This proposition was tested both cross-sectionally and longitudinally among a sample of approximately 375 men and women. Personality was operationalized in terms of the dispositional trait negative affectivity (NA), and the life circumstance investigated was health. Strong support was obtained for the hypothesized indirect effects of NA and objective health on SWB. Implications of the integrative framework for the study of SWB are discussed. PMID- 8473982 TI - Memory for positive versus negative life events: theories for the differences between happy and unhappy persons. AB - Three studies examined the following hypotheses for the relation of subjective well-being (SWB) with memory for positive versus negative life events: (a) differences in retrieval mood, (b) the incidence of positive and negative events, (c) the interpretation of events, and (d) frequency of rehearsal. In Studies 1 (n = 420) and 2 (n = 94), the partial correlation of retrieval mood with recall, controlling for SWB, was trivial, suggesting that mood had little or no effect on recall. Endorsement frequencies of positive minus negative concrete events and interpretive events on checklists in Studies 2 and 3 each correlated with SWB (ps < .001), suggesting that both incidence and interpretation contributed to the recall differences. In Study 3, the recall of 55 Ss from Study 2 was retested after an 11-month interval. The lack of an interaction between SWB and recall change suggested that rehearsal did not contribute to the recall differences. PMID- 8473983 TI - The idiographic nature of human personality: examples of the idiographic self concept. AB - Arguments are made for the practical and theoretical merits of idiographic approaches to personality. In addition, it is argued that idiographic approaches to personality afford levels of prediction that cannot be provided by nomothetic analyses, and 2 studies of the role of self-investment in interpersonal perception are presented in support of this position. Finally, in contrast to previous arguments for idiographic approaches, it is suggested that idiographic approaches to personality can provide special insight into universal patterns of human personality. PMID- 8473984 TI - Fibrin sealant adhesive systems: a review of their chemistry, material properties and clinical applications. AB - Fibrin sealants (FS) are the most successful tissue adhesives to date. They have many advantages over adhesive technologies such as cyanoacrylates and marine adhesives in terms of biocompatibility, biodegradation and hemostasis. There are several commercial products in Europe but none in the United States due to the current regulatory stance against pooled plasma blood products. Blood banks and interested investigators have implemented single- and patient autologous-donor production methods with some success. This article will review the history of FS research and development and describe the chemistry of fibrin(ogen) and the production of commercial and research products. Fibrin sealant and purified fibrin characterization is compared and contrasted. The material and adhesive properties are described, and a survey of the clinical applications in which FS has been used is included as well. PMID- 8473985 TI - Physical properties and testing methods for PTFE cardiovascular patches. AB - Patching after endarterectomy, especially carotid artery surgery, is a common procedure to repair and close the surgical site. Both synthetic and natural materials can be used, but saphenous vein is preferred due to its greater long term patency. In situations where it is not possible to use the saphenous vein, both Dacron and expanded polytetrafluoroethylene (ePTFE) patches have been used successfully. Expanded PTFE patches are readily available, soft and pliable, have excellent biocompatibility and do not require preclotting prior to implantation. Comparison of two types of ePTFE patches versus natural vessel show that they have more than adequate properties for their intended use. PMID- 8473986 TI - Surface micromorphology and cellular interactions. AB - Contact guidance induced by the topographical properties of the underlying substratum is of great importance in morphogenesis and also influences the interaction of tissue cells with implanted material. A large body of evidence has accumulated since the first detection of this phenomenon in 1910. Several major hypotheses have been developed to explain the observed cell behaviour. The technological progress enabled researchers to produce pure substrata with a defined and controlled surface microgeometry. Based on these specimens, it could be demonstrated that cytoskeletal structures and receptors forming focal adhesions most likely are involved in contact guidance. In a study using human gingival fibroblasts, the reaction of these cells to a regular surface microstructure of 1 micron pitch and 1 micron depth was tested. After two days on the microstructured samples, all the cells showed a strong alignment to the topography of the surface. Transmission electron microscopy revealed that the cells either bridged the grooves or conformed to the surface structures. The latter confirms earlier investigations with porous subcutaneous implants, where the inflammatory reaction and the formation of a fibrous tissue capsule was reduced due to enhanced tissue adhesion. PMID- 8473987 TI - Protein adsorption--effect of external lubricants at the interface. AB - Upon exposure to blood, rapid adsorption of proteins is the initial event at the contacting surface, followed by the adhesion of platelets and other blood components. Surfaces absorbing albumin appear to possess antithrombotic character in discouraging adhesion of platelets. Therefore, for the development of a blood contacting device, the interfacial events are extremely important and need serious investigation. We have attempted to observe the variations in competitive adsorption of fibrinogen and albumin onto the polyetherurethane urea (PEUU) surface in the presence of external lubricant, such as calcium stearate and silicone fluid coating. It seems, in the presence of such mediators, that fibrinogen adsorption is increased relatively with reduction in albumin at the surface. PMID- 8473988 TI - Role of soft tissue structures as an etiology of hallux limitus. AB - The authors establish common mechanical criteria for structures that can adversely affect dorsiflexion of the hallux, examine soft tissue anatomical structures around the first metatarsophalangeal joint that meet the established standards, and propose alternative methods of approaching the deformity surgically. PMID- 8473989 TI - Shin muscle activity and sports surfaces. An electromyographic study. AB - Twelve human subjects were studied to determine the effect of three different floor surfaces on the medial shin musculature during stationary running. Electromyographic equipment, gated by an accelerometer affixed to the subject's shin, was used to separate the impact (eccentric) phase from the propulsive (concentric) phase of each running step. Excessive eccentric muscle activity has been associated with increased muscle damage, and recent investigations have linked medial tibial shin pain with actual structural damage to the muscle fascial attachments to the posteromedial aspect of the tibia. Therefore, this study tends to verify the previous assumption that running on hard, noncompliant sport surfaces would predispose running and dancing athletes to shin muscle damage and resultant pain. PMID- 8473990 TI - New nonfusion procedure for talocalcaneal coalitions with a fixed heel valgus. AB - The authors present a case of bilateral middle facet talocalcaneal coalitions with peroneal spasm producing a fixed valgus heel. They introduce a corrective procedure used at the Fountain Valley Regional Hospital and Medical Center and discuss its application in podiatric surgery. Correction included resection of the synostosis and lateral opening wedge heterogenous bone graft in the calcaneus to redistribute the body's weight on the heel and centralized over the axis of the subtalar joint. PMID- 8473991 TI - Navicular drop as a composite measure of excessive pronation. AB - The measure of navicular drop has been used as an indicator of pronation at the foot. It is defined as the distance the navicular tuberosity moves in standing, as the subtalar joint is allowed to move from its neutral position to a relaxed position. The purposes of this study were to test the reliability of a method to measure navicular drop and to assess the relationships among measures of forefoot to rearfoot position, subtalar joint neutral position, and navicular drop. The results support traditional biomechanical theory but indicate that other factors contribute significantly to navicular drop. PMID- 8473992 TI - Anatomical basis for congenital deformities of the lower extremities. Part III. The foot and ankle. AB - The human foot has been characterized as a miracle of engineering and mechanical efficiency. It is a complex organ, both physiologically and structurally. The authors present a study of the foot and ankle with emphasis on the anatomy of midterm fetuses as revealed by cryomicrotomy. PMID- 8473993 TI - Retrospective study of fifth metatarsal fractures. AB - On the basis of the authors' results in treating avulsion fractures of the tuberosity, immobilization in a short leg weightbearing cast for 4 weeks is the preferred treatment. If still symptomatic at 4 weeks, some patients may require further immobilization for an additional 1 to 3 weeks. Rarely do these patients require surgery. In patients with these types of fractures, no angulation or displacement deformity was seen on x-rays, so open reduction was not warranted. Although the study does not strongly support the view that delayed healing of Jones fractures is associated with weightbearing cast treatment, the authors still tend to recommend treatment with a short leg nonweightbearing plaster cast for 6 weeks. Patients may not tolerate such treatment for this amount of time. To encourage better patient compliance, a minimum of 3 to 4 weeks in a nonweightbearing cast followed by 3 weeks in a weightbearing cast is recommended. Although open reduction was indicated in a few cases, all patients with Jones fractures, aged 20, 22, 24, 24, and 27 years, declined that option. Specifically, one patient had a delayed union of the Jones-type fracture (Fig. 4). In spite of being young and athletic, and thus at high risk for refracture, he decided against open reduction internal fixation and opted for prolonged casting. PMID- 8473994 TI - Principles of wound healing and growth factor considerations. AB - This review examines some of the important principles in wound repair and significant considerations for the use of growth factors. Moisture provides a positive influence on the mechanical and hormonal aspects of wounds. Atraumatic closure of surgical wounds and postoperative care and the types of wound closure are discussed. Cellular proliferation and migration in wounds are central features regarding growth factors. PMID- 8473995 TI - Neurilemoma presenting as a painless mass on the dorsum of the foot. AB - The neurilemoma is a benign neoplasm of Schwann's cells arising from the sheath of a nerve. This neoplasm most commonly originates from the flexor surface of the body. An unusual presentation of a neurilemoma on the extensor surface of the foot was described. The treatment plan was explained, and pathologic characteristics were outlined. Trauma as a possible etiology was also described. PMID- 8473996 TI - Case of the amazing radiographs. PMID- 8473997 TI - Evaluation of the stereoisomers of deprenyl for amphetamine-like discriminative stimulus effects in rats. AB - The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, is a phenylalkylamine derivative which is metabolized in part to l methamphetamine and l-amphetamine. As the clinical use of amphetamine-like psychostimulants is limited by their potential for abuse, we evaluated l-deprenyl for amphetamine-like discriminative stimulus effects over a range of experimental conditions. Male Fisher rats were trained under a 5-response, fixed-ratio schedule of stimulus-shock termination or a 10-response, fixed-ratio schedule of food-presentation to discriminate between d-amphetamine (1.0 mg/kg i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to l-amphetamine (1.0-2.0 mg/kg), d-deprenyl (10.0-17.0 mg/kg) and l deprenyl (17.0 and 30.0 mg/kg) under both the food-presentation and stimulus shock termination schedules, and increases in responding on the lever appropriate to d-amphetamine were dose-dependent. The dose-effect functions for l amphetamine, l-deprenyl and d-deprenyl were shifted slightly to the left under the stimulus-shock termination schedule compared to the food-presentation schedule. When l-deprenyl (3.0 or 5.6 mg/kg i.p.) was given 30 min before d amphetamine it produced a small shift to the left in the dose-effect function for d-amphetamine under the food-presentation schedule. l-Deprenyl produced clear generalization to the d-amphetamine stimulus only at very high doses of 17.0 to 30.0 mg/kg, doses about 10-fold higher than those that have a selective action on MAO-B vs. MAO-A and which start to have marked rate decreasing actions on food reinforced responding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8473998 TI - Monoamine oxidase-A inhibitors and dopamine metabolism in rat caudatus: evidence that an increased cytosolic level of dopamine displaces reversible monoamine oxidase-A inhibitors in vivo. AB - The effects of reversible inhibitors of monoamine oxidase-A (moclobemide, Ro 41 1049, both 20 mg/kg, i.p., and brofaromine, 10 mg/kg, i.p.) on the outflow of dopamine (DA) and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) as well as of 5-hydroxyindoleacetic acid was investigated by trans-striatal microdialysis in rats. These drugs markedly increased the level of DA in the dialysis fluid by 100% of basal values and concomitantly reduced the output of 3,4-dihydroxy-phenylacetic acid and homovanillic acid by 90%. The presence of tetrodotoxin in the perfusion fluid decreased the basal DA outflow and virtually abolished the rise in DA efflux after moclobemide administration. On the other hand, tetrodotoxin did not counteract the DA outflow induced by Ro 4 1284 (1 mg/kg, i.p.), a tetrabenazine derivative which rapidly releases DA from vesicles and causes a massive increase in the concentration of extravesicular amine. The injection of Ro 4-1284 30 min after moclobemide, brofaromine or Ro 41 1049 induced a 6-fold increase in DA outflow, which was accompanied by a transient increase in 3,4-dihydroxyphenylacetic acid levels. This latter effect was more marked for moclobemide than for the other two reversible inhibitors tested and was not observed in rats given the irreversible inhibitor clorgyline (5 mg/kg, i.p.). These results support the view that a large increase in the concentration of endogenous substrates in the cytosol might displace reversible monoamine oxidase-A inhibitors from the enzyme active sites. Therefore, the microdialysis technique seems to be a reliable in vivo method for assessing the degree of reversibility of monoamine oxidase inhibitors. PMID- 8473999 TI - In vitro and ex vivo inhibitory effects of L- and D-enantiomers of NG-nitro arginine on endothelium-dependent relaxation of rat aorta. AB - The in vitro and ex vivo inhibitory effects of NG-nitro-L-arginine (L-NNA) and NG nitro-D-arginine (D-NNA) on endothelium-dependent relaxations were studied in rat aortic rings. L-NNA (3 x 10(-7) to 3 x 10(-5) M) but not D-NNA (3 x 10(-6) to 3 x 10(-4) M) induced contraction of resting aortic rings and potentiated phenylephrine-induced contraction in a concentration-dependent manner. In phenylephrine-preconstricted aortic rings, L-NNA (3 x 10(-7) to 3 x 10(-5) M) and D-NNA (3 x 10(-6) to 3 x 10(-4) M) concentration-dependently inhibited the relaxation response to acetylcholine (ACh) with similar efficacies and IC50 values of 10(-6) and 3.9 x 10(-5) M, respectively. In addition, both L-NNA (3 x 10(-5) M) and D-NNA (3 x 10(-4) M) almost totally inhibited the relaxation of preconstricted rings by the calcium ionophore A 23187. The inhibitory effects of L- and D-NNA remained for at least 4 hr after the preparations were washed out. Neither the inhibitory effects of L- and D-NNA on ACh-induced relaxation nor the ACh-induced relaxation itself were affected by pretreatment with indomethacin. However, pretreatment (10 min) or post-treatment (1 hr later) with L-Arg (10(-3) M) completely prevented or markedly reversed the inhibitory effects of L- and D NNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474000 TI - Effects of drugs of abuse and cholinergic agents on delayed matching-to-sample responding in the squirrel monkey. AB - To study how drugs may disrupt short-term memory function, squirrel monkeys were trained to respond under a titrating delayed matching-to-sample schedule of reinforcement. Monkeys could respond on each of three keys in an operant chamber. At the start of each trial, the 30th response on the center key illuminated each of the side keys, one of which matched the stimulus presented on the center key (simultaneous matching). A response to the correct (matching) side key turned off all stimuli and initiated a delay, the length of which varied as a function of ongoing performance. After the delay, stimuli were randomly presented on two of the three keys. A response to the key which matched the color on the center key before the delay resulted in delivery of a food pellet (delayed matching). Incorrect simultaneous or delayed matching responses initiated a timeout. Under this procedure, diazepam and scopolamine decreased delayed matching accuracy at one or more doses that did not significantly decrease mean delay values, but only scopolamine decreased matching accuracy at a dose that did not significantly decrease response rates. Cocaine decreased mean delay values after the highest dose without affecting matching accuracy. Pentobarbital and methylscopolamine decreased matching accuracy and mean and maximum delay values after the highest doses. Nicotine and phencyclidine produced small decreases in delayed matching accuracy without affecting mean and maximum delay values. Caffeine, morphine, physostigmine and neostigmine did not alter matching performance even after doses that markedly decreased rates of responding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474001 TI - Acute opioid dependence in the cardiovascular system of the spinal rat. AB - This article analyzes and characterizes the early development of opioid dependence in the cardiovascular system of the spinal rat. The main part of the study deals with changes in mean arterial pressure and heart rate induced by naloxone (NLX) in spinal rats pretreated with single doses of morphine. The results show that the cardiovascular system of the spinal rat is highly sensitive to the abstinence-precipitating actions of NLX after a single dose of morphine. Dose-response curves for precipitated abstinence evaluated as changes in mean arterial pressure and heart rate show a gradual increase in maximum followed by a progressive shift to the left as dependence progresses. Cardiovascular abstinence is mostly mediated by catecholaminergic systems. NLX also precipitates noncardiovascular signs of abstinence. Interestingly, morphine-free spinal rats gave some abstinence-like responses to NLX, probably because of endogenous release of opioids. The spinal rat seems to be a valuable system for a rapid quantitative pharmacological characterization of the abstinence-precipitating actions of opioid antagonists and for the study of the changes that occur during the acute development of opioid dependence. PMID- 8474002 TI - Reversal of gallium arsenide-induced suppression of the antibody-forming cell response by vehicle supernatants. II. Nature and identification of reversing factors. AB - Previous studies have demonstrated that several immunological events which are T cell mediated are significantly suppressed by a single exposure to gallium arsenide (GaAs). In addition, in the in vitro-generated antibody-forming cell (AFC) response supernatants from vehicle (VH) cultures were able to time dependently reverse suppression induced by either in vivo (200 mg/kg) or in vitro (50 microM) exposure to GaAs. The present studies were designed to determine the nature and identification of the reversing factors present in VH supernatants. VH supernatants (25-100%) were able to dose-dependently reverse suppression of the AFC response (from 45% suppression to 48% enhancement of the VH response) induced by GaAs exposure (200 mg/kg). Concentration of 24-hr VH supernatants and treatment with proteinases revealed that the reversing factors were protein in nature with a molecular weight between 5,000 and 50,000 Da. This molecular weight range encompasses many of the lymphokines known to be necessary for the generation of an immune response. In antibody cultures exposed either in vivo or in vitro to VH or GaAs, HT-2 bioassay and antigen capture enzyme-linked immunosorbent assays demonstrated that GaAs exposure alters production of interleukin (IL)-2, IL-4, IL-5 and IL-6. Interestingly, the alterations in lymphokine production differed between the exposure regimes. Direct addition of IL-2 to antibody cultures resulted in a dose-dependent (6.25-50 ng/ml) reversal of GaAs-induced suppression (in vivo exposure) and was also dependent on the concentration of GaAs (50-200 mg/kg). IL-4 suppressed the VH AFC response and failed to reverse GaAs suppression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474003 TI - Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: II. Effect of pertussis and cholera toxins. AB - The injection of 1 microgram of pertussis toxin, which inactivates Gi/o proteins, in the rat dorsal raphe nearly abolished the responsiveness of serotonin (5-HT) neurons to microiontophoretic applications of 5-HT and selective 5-HT1A agonist 8 hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) without altering their responsiveness to of gamma-aminobutyric acid (GABA). In contrast, the injection of 1 microgram of cholera toxin, which causes an activation of Gs proteins, did not alter the responsiveness of 5-HT neurons to 5-HT, 8-OH-DPAT or GABA. Such in situ injection of either toxin in the dorsal hippocampus decreased by about 90% the responsiveness of CA3 pyramidal neurons to microiontophoretic applications onto their cell body of 5-HT and 8-OH-DPAT, but not of GABA. The effectiveness of the stimulation of the ascending 5-HT pathway in suppressing the firing activity of the same neurons, which results from the release of 5-HT at the level of their dendritic tree, was also markedly decreased in the cholera toxin-treated rats, but intriguingly not in the pertussis toxin-treated rats. These results indicate that, on 5-HT neurons, the somato-dendritic 5-HT1A autoreceptor is coupled to Gi/o, but insensitive to the persistent activation of Gs proteins. In the CA3 region of the hippocampus, there would be two subsets of postsynaptic 5-HT1A receptors on the pyramidal neurons: those apposed to 5-HT terminals on their dendritic tree (denoted intrasynaptic) and those located on their cell body (denoted extrasynaptic). The former are cholera toxin sensitive, whereas the latter are sensitive to both pertussis and cholera toxins. PMID- 8474004 TI - Characterization of vascular postsynaptic neuropeptide Y receptor function and regulation. 1. NPY-induced constriction in isolated rat femoral artery rings is mediated by both Y1 and Y2 receptors: evidence from benextramine protection studies. AB - Neuropeptide Y (NPY), a potent pressor agent and vasoconstrictor, is thought to contribute to the sympathetically mediated postsynaptic regulation of blood pressure primarily through activation of vascular Y1 rather than Y2 NPY receptors. However, data are available that conflict with this conclusion. In this article, the relative roles of postsynaptic Y1 and Y2 receptors as mediators of direct NPY-induced isolated rat femoral artery ring vasoconstriction were evaluated through use of selective Y1 and Y2 agonists, [Leu31, Pro34]NPY ([Leu, Pro]NPY) and NPY13-36 [NPY(13-36)], respectively, and the NPY receptor antagonist benextramine (BXT). NPY, [Leu, Pro]NPY and NPY(13-36) were equipotent as vasoconstrictors, and constriction induced by each peptide, but not by the calcium channel agonist BAY K 8644 (BAY), was almost completely blocked by 10 microM BXT. Each of the three peptides also induced self- and cross desensitization and protection from BXT blockade, except that [Leu, Pro]NPY neither desensitized nor protected NPY(13-36)-associated responses. NPY also failed to protect [Leu, Pro]NPY- and NPY(13-36)-elicited constriction, and NPY(13 36) failed to provide self-protection, from BXT blockade. However, in these instances, as opposed to the [Leu, Pro]NPY-NPY(13-36) cross-protection experiments, the occurrence of protection was probably masked by the relatively large magnitude of desensitization concurrently induced by the protecting peptide. Taken together, the present findings suggest that NPY-induced rat femoral artery vasoconstriction is mediated by separate, BXT-sensitive, postsynaptic Y1 ([Leu, Pro]NPY-activated) and Y2 [NPY(13-36)-activated] receptors. PMID- 8474005 TI - Effects of quinapril, a new angiotensin-converting enzyme inhibitor, on vasoconstrictor activity in the isolated, perfused mesenteric vasculature of hypertensive rats. AB - Previously, we had reported that 7-day administration of the angiotensin converting enzyme inhibitor quinapril markedly reduced electrically evoked pressor responses in the isolated, perfused mesenteric vascular bed of the spontaneously hypertensive rat (SHR). In the present study, we investigated the possibility that quinapril alters postsynaptic vasoconstrictor activity to a variety of vasoconstrictive agents. Quinapril (10 mg/kg/day), administered orally to SHR for 7 days, significantly reduced the potency and the maximal vasopressor response to phenylephrine (2.5-fold and 40%, respectively) and the maximal response to serotonin (50%) compared with the responses from vehicle treated SHR. In contrast, quinapril had no significant effect on the pressor responses to KCl or phorbol ester. Furthermore, an equipotent antihypertensive dose of hydralazine (5 mg/kg/day, p.o., for 7 days) exerted no inhibitory effect on the pressor responses elicited by phenylephrine, KCl phorbol ester, but significantly reduced the maximal response to serotonin. In addition, vasopressor responses to phenylephrine were not affected by an acute (i.e., 75 min) infusion of quinaprilat, the active metabolite of quinapril. The results suggest that 7-day quinapril administration, and not acute treatment, reduces alpha 1 adrenoceptor and S2-serotonergic receptor-mediated vasoconstriction. However, quinapril did not reduce the vasoconstrictor responses induced by KCl or phorbol ester, indicating that those pressor responses that are due to depolarization or protein kinase C activation are, in part, independent of angiotensin-converting enzyme inhibition. This inhibition of vascular alpha 1 adrenoceptor and S2-serotonergic receptor pressor activity may underlie, in part, the long-term antihypertensive activity of quinapril in the SHR. PMID- 8474006 TI - Mechanism of the bradycardia produced in the cat by the anticholinesterase neostigmine. AB - Neostigmine evoked bradycardia in vagotomized, propranolol-treated cats. Heart rate decreased by 50% with 0.4 +/- 0.2 mg/kg (mean +/- S.D.) i.v. of neostigmine. The bradycardia was attenuated after acetylcholine (ACh) depletion in the cardiac parasympathetic pathway suggesting ACh release within this pathway was involved. The bradycardia was unchanged after preganglionic terminal degeneration suggesting ACh release was from cardiac ganglion cells. Edrophonium produced a much weaker bradycardia suggesting the anticholinesterase effect of neostigmine may not produce the bradycardia. The neostigmine-induced bradycardia was blocked by systemic atropine (ED50, 0.005 +/- 0.001 mg/kg), pancuronium bromide (ED50, 0.033 +/- 0.021 mg/kg), pirenzepine (ED50, 74.7 +/- 7.9 micrograms/kg), hexamethonium (ED50, 8.3 +/- 1.6 mg/kg) and d-tubocurarine (ED50, 8.6 +/- 3.0 micrograms/kg). The doses of hexamethonium and d-tubocurarine that blocked the neostigmine-induced bradycardia were significantly higher than required for blocking the bradycardia produced by vagus nerve stimulation. Hexamethonium (60 mg/kg i.v.) had no effect on the bradycardia produced by the muscarinic agonist methacholine (100-300 micrograms/kg/min i.v.). The dose of pirenzepine that blocked the neostigmine-induced bradycardia was lower than required for blocking the bradycardia produced by vagus nerve stimulation. McN-A-343 ([4-hydroxy-2 butynyl]-1-trimethyl ammonium m-chlorocarbanilate chloride) (1 mg/kg i.v.) did not produce bradycardia. These observations suggest neostigmine evokes bradycardia by activation of ACh receptors on cardiac ganglion cells producing ACh release and activation of cardiac M2 receptors. The low sensitivity of the neostigmine-induced bradycardia to pirenzepine, and the failure of McN-A-343 to evoke bradycardia, suggest the receptor on cardiac ganglion cells is not an M1 type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474007 TI - (+-)-N6-endonorbornan-2-yl-9-methyladenine (N-0861) and its enantiomers: selective antagonists of A1-adenosine receptors in guinea pig isolated atria. AB - Adenosine and its metabolically stable analog 5'-N-ethylcarbox-amidoadenosine (NECA) induce negative inotropic, chronotropic and dromotrpic actions in the heart through activation of A1-adenosine receptors and relaxation of vascular smooth muscle through activation of A2-adenosine receptors. In vitro studies were carried out in order to determine the potency of the antagonist (+-)-N6 endonorbornan-2-yl-9-methyladenine (N-0861) and its two component enantiomers, WRC-0006(+) and WRC-0007(-), at the A1 receptors in the guinea pig atria and the A2 receptors in the guinea pig aorta. N-0861 competitively antagonized the negative inotropic responses induced by NECA in the eletrically paced left atrium (pKB = 6.24) and the negative chronotropic responses induced by NECA in the spontaneously beating right atrium (pKB = 6.29). WRC-0007 was 4-fold more potent (pKB = 6.51) than WRC-0006 (pKB = 5.86) at antagonizing the A1-adenosine receptors in the guinea pig left atrium. N-0861, WRC-0007 and WRC-0006 at high concentrations (> 3 x 10(-5) M) produced direct relaxations of the guinea pig aorta that masked to a small extent the A2 receptor antagonism by these compounds. The affinities of the antagonists for the A2 receptor in the aorta were calculated using the method of pharmacological resultant analysis. N-0861 was 47-fold less potent at the A2 receptor (pKB = 4.57) than it was at the A1 receptor. WRC-0006 was 2-fold more potent (pKB = 4.81) than WRC-0007 (pKB = 4.52) at the A2-adenosine receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474008 TI - Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. AB - Although a receptor exists for cannabinoid drugs, it is uncertain which pharmacological actions this receptor mediates. This structure-activity relationship investigation was initiated to determine which effects might correspond to binding affinity for the cannabinoid receptor, as well as to explore the binding requirements of this site. The ability of nearly 60 cannabinoids to displace [3H]CP-55,940 [(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-4-[3-hydroxy propyl] cyclohexan-1-ol] was determined before establishing correlations between receptor affinity and in vivo pharmacological potency. Analysis of [3H]CP-55,940 binding indicated a Hill coefficient of 0.97, a Bmax of 499 pM (3.3 pmol/mg of protein) and an apparent Kd of 924 pM. Closer inspection indicated the binding assay exhibited "zone B" characteristics, and use of correction equations indicated a true Kd for CP-55,940 of 675 pM. The structure activity relationship indicated the importance of side chain structure to high affinity binding, with the most potent analogs (K1 < 10 nM) possessing either a dimethylheptyl side-chain, a similarly complex branched side chain or a halogen substituent at the 5' position. Comparative analysis of K1 values to in vivo potency in a mouse model indicated a high degree of correlation between parameters for the depression of spontaneous locomotor activity (r = 0.91) and for the production of antinociception (r = 0.90), hypothermia (r = 0.89) and catalepsy (r = 0.85). Similarly high correlations were demonstrated between binding affinity and in vivo potency in both the rat drug discrimination model (r = 0.81) and for psychotomimetic activity in humans (r = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474009 TI - GM1 ganglioside treatment of focal ischemia: a dose-response and microdialysis study. AB - The efficacy of GM1 ganglioside treatment in stroke was studied in a permanent middle cerebral artery occlusion model in the rat. A dose-dependent attenuation of infarct size at 24 hr was documented with the maximum effective dose halving the volume of the experimental stroke. Delayed administration at 5 min, but not 15 min, after vessel occlusion was as effective as preocclusion drug administration. Morphologic sparing was confined to the cortical penumbra; no protection in the ischemic core was found. Morphologically salvaged cortex was also metabolically preserved as demonstrated by quantitative measurement of glucose utilization. In vivo microdialysis demonstrated an attenuation of ischemic-induced glutamate release in the cortex with GM1 administration but no effect was found in the caudate. Hypotension did not occur even with doubling of the maximally effective dose of GM1. Accordingly, GM1 may be a safe and effective treatment for stroke. PMID- 8474010 TI - 2-Phenylethoxy-9-methyladenine: an adenosine receptor antagonist that discriminates between A2 adenosine receptors in the aorta and the coronary vessels from the guinea pig. AB - Substituting a methyl group for the ribose moiety of N6-substituted adenosines that are selective agonists at the adenosine A1 receptor creates antagonists that are A1-selective. Inasmuch as 2-phenylethoxyadenosine is a selective agonist for the adenosine A2 receptor, 2-phenylethoxy-9-methyl-adenine (PEMA) was synthesized and tested as a potential adenosine A2 receptor antagonist. In guinea pig hearts, PEMA antagonized with the same potency (pKB approximately 6.1) the A1-mediated negative dromotropic and inotropic actions and the A2-mediated coronary vasoactivity of the nonselective adenosine receptor agonist 5'-N ethylcarboxamidoadenosine (NECA). PEMA at concentrations up to 30 microM did not antagonize the NECA-induced relaxations in guinea pig aortic rings. At concentrations exceeding 10 microM, PEMA caused xanthine-insensitive relaxations of both the aorta and the coronary vessels. Pharmacological resultant analysis revealed A2 receptor antagonism by PEMA in the guinea pig aorta (pKB = 5.2). The nonselective adenosine receptor antagonist 8-p-sulfophenyl-theophylline antagonized NECA responses in all four assays with equal potency (pKB approximately 5.7). Thus, PEMA does not discriminate between A2 receptors in the coronary vessels and A1 receptors in the atria of the guinea pig, but it is 10 fold more potent at antagonizing the A2 receptor in coronaries than the A2 receptors in the aorta. The data suggest that the A2 receptors in the coronary vasculature may be of the A2a subtype, whereas those in the aorta may be of the A2b subtype. PMID- 8474011 TI - N-aralkyl derivatives of 1-aminobenzotriazole as potent isozyme-selective mechanism-based inhibitors of rabbit pulmonary cytochrome P450 in vivo. AB - Two N-aralkylated (N-benzyl-and N-alpha-methylbenzyl-) derivatives of 1 aminobenzotriazole, a mechanism-based inhibitor of cytochrome P450 with low isozyme selectivity, were previously shown to be potent and isozyme-selective suicide substrates for rabbit and guinea pig pulmonary P450 in vitro (Mathews and Bend, 1986; Woodcroft et al., 1990). These three compounds were compared as inhibitors in vivo after i.v. administration to rabbits treated with the cytochrome P450 inducers beta-naphthoflavone or phenobarbital. By 1 hr after administration of N-alpha-methylbenzyl-1-aminobenzotriazole (1 mumol/kg), 80% of P450 2Bs-catalyzed benzphetamine N-demethylation in lung of beta-naphthoflavone treated rabbits was inactivated and about 35% of P450 was lost without inhibition of P450 1A1-catalyzed activity; at a dose of 10 or 100 mumol/kg, this compound totally inactivated pulmonary P450 2Bs activity while exerting minimal effects on benzphetamine N-demethylation activity (< 20% inhibition) in liver of beta naphthoflavone-treated rabbits. N-benzyl-1-aminobenzotriazole was also an isozyme and tissue-selective inhibitor of pulmonary P450 2Bs in vivo. Relatively high doses (100 mumol/kg) of these compounds were compared in phenobarbital-induced rabbits. Virtually all (> or = 95%) of pulmonary P450 2Bs-dependent activity was inhibited by the two N-aralkylated compounds (vs. 50% for 1-aminobenzotriazole). At this dose, about 25% of hepatic P450 was destroyed by all three compounds, whereas 1-aminobenzotriazole and its N-benzyl and N-alpha-methylbenzyl derivatives inactivated 20, 50 and 85% of hepatic P450 2Bs-selective benzphetamine N-demethylation activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474012 TI - Expression of ganglia-type nicotinic acetylcholine receptors and nicotinic ligand binding sites by cells of the IMR-32 human neuroblastoma clonal line. AB - Studies were conducted to ascertain whether cells of the IMR-32 human neuroblastoma clone express ligand binding sites and functional responsiveness attributable to ganglia-type nicotinic acetylcholine receptors (nAChR) and/or neuronal/nicotinic alpha-bungarotoxin binding sites. Some comparative studies were conducted using cells of other clonal lines, including BC3H-1 mouse muscle line cells that are known to express muscle-type nAChR. Two classes of specific binding sites for 3H-labeled acetylcholine ([3H]ACh) and a single class of high affinity, specific 125I-labeled alpha-bungarotoxin binding sites are expressed on membrane fractions prepared from IMR-32 cells. Radioligand binding to these sites on IMR-32 cells is relatively insensitive to blockade by the muscle-type nAChR selective inhibitors, succinyldicholine and decamethonium, indicating that they are distinct from muscle-type nAChR. [3H]ACh binding to its sites on IMR-32 cell membranes is insensitive to blockade by alpha-bungarotoxin, indicating that IMR 32 cell [3H]ACh and 125I-labeled alpha-bungarotoxin binding sites also can be distinguished. Functional nAChR ion channels of the ganglia-type are expressed by IMR-32 cells, as assessed by the abilities of nicotinic agonists to stimulate 86Rb+ efflux, the relatively higher sensitivity of those responses to blockade by mecamylamine than by d-tubocurarine, and the inability of alpha-bungarotoxin to antagonize nAChR function. These results are consistent with expression by IMR-32 cells of functional ganglia-type nAChR that correlate with high affinity [3H]ACh binding sites as well as expression of a distinct class of neuronal/nicotinic alpha-bungarotoxin binding sites that have a ganglia-type pharmacology. PMID- 8474013 TI - Antiproliferative and endothelium-dependent vasodilator properties of 1,3-dihydro 3-p-chlorophenyl-7-hydroxy-6-methyl-furo-(3,4c) pyridine hydrochloride (cicletanine). AB - The vasodilator and antiproliferative actions of 1,3-dihydro-3-p-chlorophenyl-7 hydroxy-6-methyl-furo-(3,4c) pyridine hydrochloride (cicletanine) were studied on mesenteric resistance arteries and cultured mesenteric artery myocytes of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Cicletanine (20-200 microM) induced relaxation of endothelium-intact mesenteric resistance arteries of SHR and WKY precontracted with norepinephrine. No difference in sensitivity was observed (SHR IC50 = 77 +/- 12 microM vs. 83.3 +/- 7.4 microM for WKY, N.S.). Endothelial denudation of WKY vessels significantly attenuated the relaxing action of cicletanine (IC50 + endo = 83 +/- 7.4 microM vs. IC50 - endo = 135 +/- 9.7 microM; P < .001) and had a similar, but nonsignificant effect on SHR (IC50 + endo = 77 +/- 12 microM vs. IC50 - endo = 117 +/- 14.5 microM; P = .065). Preincubation of endothelium-intact vessels with nitro-L-arginine methyl ester significantly attenuated cicletanine-induced relaxation in WKY, but not SHR vessels; 0.1 mM Ba++ had a similar effect. Preincubation with 3 microM indomethacin was without effect on relaxation of vessels of either strain. Cicletanine (100-1000 microM) inhibited proliferation of cultured superior mesenteric artery muscle cells growing in the presence of either 10% (SHR IC50 = 440 +/- 24 microM vs. 517 +/- 12 microM for WKY; P < .05) or 2% fetal bovine serum. This antiproliferative action was fully reversible, partially inhibited by indomethacin in SHR myocytes and was associated with a decrease in [3H]thymidine uptake in both strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474014 TI - Epidermal growth factor and transforming growth factor-alpha directly inhibit parietal cell function through a similar mechanism. AB - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are naturally occurring peptides which are present throughout the gastrointestinal tract and are capable of inhibiting gastric acid secretion. Although previous studies have suggested that TGF-alpha may serve as an autocrine factor regulating parietal cell function, the cellular mechanisms by which it exerts its inhibitory action have not been fully elucidated. In addition, no systematic comparison has been undertaken of the effects of EGF and TGF-alpha on parietal cell function. The aims of the present studies were to compare the actions of EGF and TGF-alpha on basal and stimulated acid secretion by isolated rabbit parietal cells and to elucidate the intracellular mechanisms by which these growth factors inhibit acid secretion stimulated by agents that activate the adenylate cyclase and cyclic AMP second messenger system. Although EGF and TGF-alpha did not alter basal parietal cell function, they both inhibited histamine-stimulated [14C]aminopyrine accumulation in a identical time- and dose dependent fashion. The maximal effect of approximately 40% inhibition for histamine-stimulated action was achieved with concentrations of 10(-6) M for both EGF and TGF-alpha. The inhibitory effect of EGF and TGF-alpha appeared to be at the postreceptor level as neither growth factor significantly altered binding of histamine to its receptor (H2) on parietal cells. Consistent with this postulated mechanism of action, both EGF and TGF-alpha dose-dependently inhibited forskolin stimulated aminopyrine uptake with IC50 similar to those required for inhibiting the stimulatory effect of histamine. Of note, neither growth factor inhibited parietal cell activity stimulated by dibutyryl cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474015 TI - Chronic physical activity alters hepatobiliary excretory function in rats. AB - Recent studies have indicated that exercise causes alterations in the biotransformation of some xenobiotics and the clearances of antipyrine and [14C]aminopyrine. The present study has investigated whether chronic voluntary physical activity alters hepatobiliary excretory function by comparing the clearance and biliary excretion of model substrates for each of four carrier mediated transport systems (anion, uncharged, bile acid and cation; n = 8 for each chemical in each group) in active and inactive female rats. The active rats had access to running wheels and voluntarily ran 11.2 +/- 0.68 km/day. The active rats were fed ad libitum, and ate 37% more food than weight-matched, restricted fed sedentary control rats. Basal bile flow was 34% higher in active rats than in inactive rats, and excretion of bile acids, cholesterol and phospholipid were also increased. The biliary excretion and biliary clearance of the anion, indocyanine green, were elevated in active rats, although total clearance and serum concentrations were not different due to decreased non-biliary clearance. Serum elimination and total clearance of the uncharged substrate, ouabain, were elevated in the active rats, due entirely to increased nonbiliary clearance. Total clearance of the bile acid, taurocholate, was higher in active rats due to an increased biliary clearance. In contrast, there were no differences in either the biliary excretion or clearances of the cation, procainamide ethobromide, between the two groups of rats. Finally, no differences in volume of distribution or elimination half-life were noted between inactive and active rats for any of the substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474016 TI - Pharmacological characterization of the renovascular P2 purinergic receptors. AB - Isolated rat kidneys, perfused at a constant flow with a nonrecirculated medium, were used to investigate the effects of P2 purinergic receptor agonists on renal vascular resistance. A potent P2y agonist, 2-methylthio ATP, dilated the kidney in a concentration-dependent manner, a response that was similar to that elicited by acetylcholine. The vasodilator responses to 2-methylthio ATP and to acetylcholine were nearly abolished by N omega-nitro-/-arginine methyl ester, an antagonist of nitric oxide formation by endothelial cells. A potent P2x agonist, alpha, beta-methylene ATP, constricted the kidney in a concentration-dependent manner, and the effect was potentiated by N omega-nitro-/-arginine methyl ester. This latter finding suggests that alpha,beta-methylene ATP activates P2y receptors, but with such a low potency that any tendency for vasodilation is masked by the predominant P2x receptor-induced constriction. Collectively, the results indicate the renal vasculature can either constrict or dilate in response to P2 purinergic receptor agonists, depending upon which subclass of receptor is activated, P2x (constrict) or P2y (dilate). Furthermore, the P2y receptor-induced vasodilation appears to be mediated by endothelial cell nitric oxide formation. PMID- 8474017 TI - Role of nitric oxide in neurogenic vasodilation of porcine cerebral artery. AB - A superfusion bioassay cascade, with porcine pial arteries as donor tissues and rabbit aortic rings as detector tissues, was used to examine the role of nitric oxide (NO) in cerebral nonadrenergic, noncholinergic neurogenic vasodilation. All arteries were mechanically denuded of endothelium. In the presence of atropine (1 microM) and guanethedine (0.3 microM), transmural nerve stimulation (TNS) of cerebral arteries (CA) resulted in a frequency-dependent relaxation of phenylephrine-precontracted aortic rings. Relaxation was abolished by tetrodotoxin (2 microM) superfused onto and by cold-storage denervation of CA, suggesting that a vasodilating factor (VF) of neuronal origin in CA was released upon TNS. The VF-induced relaxation was inhibited by NW-nitro-L-arginine (0.3 mM) superfused onto CA. This inhibition was reversed by L-arginine (0.3 mM) but not D arginine (0.3 mM). Exogenously applied NO onto CA also induced dilations of aortic rings in a concentration-dependent manner. The VF- and NO-induced dilations, which were abolished by hemoglobin (0.3 microM), and enhanced by superoxide dismutase (30 U/ml), declined to the same extent with similar time courses from the first to the second aortic ring. These findings indicate that VF and NO possess a similar labile nature and half-life, suggesting that VF is NO or a related substance. Identical frequency-response curves of TNS (2-16 Hz) and concentration-response curves of NO (10-1000 nM) further suggest that < 1000 nM of NO was released from CA upon TNS at the maximal frequency used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474018 TI - Barbiturate anesthetics depress the resting K+ conductance of myocardium. AB - The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ramp command potentials from -120 to +60 mV at a rate of 20 mV/sec revealed that 30 microM thiopental also depressed the delayed outward K+ current by 25 +/- 4% (n = 4). Examination of other barbiturates revealed that the potency in the suppression of IK1 was related to the octanol/water partition coefficient, suggesting a lipophilic site of action. Utilizing guinea pig ventricular myocytes, we observed a similar level of IK1 depression with thiopental, however the rates of onset and recovery were considerably slower than with frog atrial myocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474019 TI - Serotonin-facilitated dopamine release in vivo: pharmacological characterization. AB - The receptor specificity of serotonin (5-HT) agonist-induced facilitation of dopamine (DA) release was assessed by using in vivo microdialysis. The 5-HT receptor selective agonists RU 24969 [5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl) 1H indole succinate], 2-methylserotonin maleate, 5-methoxytryptamine HCl, 8 hydroxy-2-(di-n-propylamino) tetralin hydrobromide and 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane HCl were perfused through probes located in the anterior lateral striata of chloral hydrate-anesthetized rats. The agonists increased extraneuronal levels of DA in a dose-dependent manner, suggesting receptor selectivity in the order of 5-HT1b > 5-HT4 >> 5-HT2 = 5-HT1a. Coperfusion of the 5-HT1 antagonist pindolol with RU 24969 reduced the efficacy of RU 24969. The 5-HT2 antagonist ritanserin (6-[2-[4[bis(4 fluorophenyl)methylene]-1-piperadinyl]- ethyl]-7-methyl-5H-thiazolo[3,2 a]pyrimidin-5-one) did not antagonize the effect of either 5-HT or 1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane HCl on DA levels. MDL 72222 (3-tropanyl 3,5-dichlorobenzoate) and ICS 205930 (3-tropanyl-indole-3-carboxylate), both 5 HT3 antagonists, decreased the efficacy of 5-HT. The partial 5-HT4 antagonist ICS 205930 reduced DA released by perfusion of the 5-HT1/2/4 agonist 5 methoxytryptamine HCl. Coperfusion of antagonists with agonists indicated involvement of 5-HT1 and 5-HT3 receptors and a lack of involvement of 5-HT2 receptors in the 5-HT-induced facilitation of DA release. Determination of the role of 5-HT4 receptors will require additional work with more selective ligands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474020 TI - Inhibition and induction of cytochrome P450 isoenzymes in rat lung. AB - The O-dealkylation of pentoxyresorufin, a substrate for P450 2B1, was decreased in lung microsomes from rats dosed with O,O,S-trimethylphosphorodithioate, O,O,O trimethylphosphorothioate, bromophos, fenitrothion, p-xylene and 2,4-dichloro-(6 phenylphonoxy)ethylamine. This activity was decreased by antibodies to P450 2B1 but unaffected by antibodies to P450 1A1 or 4B1. This reduction reflected both inactivation and destruction of P450 2B1; destruction of this protein was particularly marked after bromophos and fenitrothion. Pyrazole was the only compound in this study to induce the O-dealkylation of pentoxyresorufin. None of these compounds altered the rate of ethoxyresorufin O-dealkylation, an indicator of P450 1A1 activity, but this activity was induced greatly by both Aroclor and beta-naphthoflavone, p-Xylene was the only compound to decrease P450 4B1 activity, as determined by the N-hydroxylation of 2-aminofluorene. In the liver, bromophos, fenitrothion, p-xylene and 2,4-dichloro-(6-phenylphonoxy)ethylamine all had marked effects on the O-dealkylation of ethoxyresorufin and pentoxyresorufin but, at the dose used, O,O,O-trimethylphosphorothioate and O,O,S trimethylphosphorodithioate had minimal effects in this tissue. Thus, both O,O,O trimethylphosphorothioate and O,O,S-trimethylphosphorodithioate are exquisitely selective inhibitors of pulmonary P450 2B1 activity. Their use, together with pyrazole, will facilitate future studies of the pulmonary activation of toxins by P450 2B1. PMID- 8474021 TI - Mitochondrial and glycolytic dysfunction in lethal injury to hepatocytes by t butylhydroperoxide: protection by fructose, cyclosporin A and trifluoperazine. AB - In isolated mitochondria, t-butylhydroperoxide (t-BuOOH) and other pro-oxidants cause a permeability transition characterized by increased permeability to small ions, swelling and loss of membrane potential. Cyclosporin A and trifluoperazine inhibit this permeability transition. Here, we investigated the role of the mitochondrial permeability transition in lethal cellular injury from t-BuOOH. Hepatocytes from fasted rats were isolated by collagenase perfusion, and cell viability was assessed by propidium iodide fluorescence. t-BuOOH caused dose- and time-dependent cell killing. Fructose, a substrate for glycolytic ATP formation, protected at lower (< or = 100 microM), but not at higher concentrations of t BuOOH. In fructose-treated cells, oligomycin (10 micrograms/ml) delayed cell killing after 100 to 300 microM t-BuOOH, whereas cyclosporin A (0.5 microM) plus trifluoperazine (5 microM) even more potently reduced lethal injury. In hepatocyte suspensions, 100 microM t-BuOOH caused mitochondrial depolarization as determined by release of rhodamine 123. Cyclosporin A plus trifluoperazine in the presence of fructose substantially reduced release of rhodamine 123. Similarly, in single cultured hepatocytes viewed by laser scanning confocal microscopy, t BuOOH caused leakage of rhodamine 123 from mitochondria, an event which preceded cell death and which was delayed by fructose in combination with cyclosporin A plus trifluoperazine. At 1 mM, t-BuOOH inhibited glycolysis, and fructose in combination with either oligomycin or cyclosporin A plus trifluoperazine had only a short-lived protective effect. In conclusion, t-BuOOH toxicity was progressive with increasing dosages. At low t-BuOOH (< or = 50 microM), mitochondrial ATP synthetic capacity was inhibited, but not uncoupled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474022 TI - Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. AB - Kinetic and inhibitor studies using cDNA-expressed enzymes and human liver microsomes have characterized the specificity of a range of cytochrome P450 (CYP) 1A substrate and inhibitor probes towards the two isoforms comprising this subfamily. Expressed CYP1A1 and CYP1A2 both catalyzed the O-deethylation of phenacetin, although the apparent Km was about 4-fold lower for CYP1A2 (25 vs. 108 microM). Phenacetin O-deethylation exhibited biphasic kinetics in human liver microsomes, and the apparent Km for the high-affinity component (9 +/- 6 microM) was consistent with the involvement of CYP1A2 in this reaction. The prototypic CYP1A xenobiotic inhibitor and substrate probes alpha-naphthoflavone, ellipticine, 7-ethoxycoumarin and 7-ethoxyresorufin all inhibited CYP1A1- and CYP1A2-mediated phenacetin O-deethylation as well as the high-affinity component of human liver phenacetin O-deethylase activity. alpha-Naphthoflavone and 7 ethoxycoumarin were, however, approximately 10-fold more potent as inhibitors of CYP1A2 than CYP1A1. Other putative human CYP1A xenobiotic substrates and inhibitors, including caffeine, 5- and 8-methoxypsoralen, nifedipine, paraxanthine, propranolol and theophylline similarly inhibited CYP1A1- and 1A2 catalyzed phenacetin O-deethylation and the high-affinity human liver phenacetin O-deethylase. In contrast, the monoclonal antibody MAb 1-7-1, raised against 3 methylcholanthrene-inducible rat cytochromes 450, almost abolished CYP1A1 mediated phenacetin O-deethylation, but had no effect on human liver microsomal- or CYP1A2-catalyzed phenacetin dealkylation. Together with previous data, the results indicate that the majority of human CYP1A xenobiotic inhibitor and substrate probes are nonspecific in their recognition of CYP1A1 and CYP1A2, although selectivity is apparent for some compounds. PMID- 8474023 TI - Plasma stability and pharmacokinetics of radiolabeled deferoxamine-biotin derivatives. AB - The extraordinary high affinity of biotin for streptavidin may be exploited in a two-step in vivo approach for delivering radiolabeled biotin derivatives suitable for imaging and therapy to lesion-bound streptavidin-conjugated monoclonal antibodies. Compared to the use of directly radiolabeled monoclonal antibodies, the two-step approach is desirable because of the fast renal clearance of radiobiotin, which reduces in vivo background levels and radiation dose. Deferoxamine binds with high-affinity trivalent metals useful for imaging and radiotherapy. Three deferoxaminebiotin derivatives were synthesized, radiolabeled and their stabilities tested in vitro in dog plasma and in vivo in the dog by an avidin binding assay and high-performance liquid chromatography. Defero desaminolysyl-biotin (DLB) was unstable, with immediate degradation evident. A plasma enzyme, biotinidase, converts biocytin to biotin. DLB closely resembles biocytin, and analysis of the urine and plasma suggested rapid degradation of DLB to biotin and desaminolsyl-deferoxamine. Defero-biotin, a direct conjugate of deferoxamine and biotin, was similarly tested and found to be more stable. Defero acetyl-cysteinyl-biotin contains a carboxyl group adjacent to the amide bond cleavage site of biotinidase. In vitro at 24 hr in plasma, defero-acetyl cysteinyl-biotin was 87% stable, compared to 45% and 15% for defero-biotin and DLB, respectively. The pharmacokinetics of the three derivatives were similar, with 80% of the injected doses found in the urine at 6 hr; however, only defero acetyl-cysteinyl-biotin was present as the intact moiety. PMID- 8474024 TI - Induction of tolerance to crotoxin in mice. AB - Crotoxin, the major toxic component from the venom of Crotalus durissus terrificus is a potent neurotoxin (LD50, i.p., mice, 0.09 mg/kg) which possesses phospholipase A2 activity and causes a blockade of neuromuscular transmission. In this article, we show that mice injected daily with progressively increasing doses of crotoxin develop tolerance to the lethal action of this toxin. Treated mice tolerated daily doses of crotoxin 20- to 35-fold higher than the original LD50 without the characteristic signs of toxicity. Studies on the isolated phrenic nerve-diaphragm preparation in vitro from control (crotoxin-naive) mice showed that the exposure to 2 to 10 micrograms/ml crotoxin in the bath produced complete transmission blockade in 120 to 150 min. Conversely, the preparations from crotoxin-treated mice required crotoxin concentrations in the range of 17.5 to 100 micrograms/ml to produce complete neuromuscular block, being virtually insensitive during 200 min of exposure to 5 to 10 micrograms/ml crotoxin. Phrenic nerve-diaphragm preparations of control (crotoxin-naive) and crotoxin-treated mice did not show significant differences in sensitivity to the blocking action of carbamylcholine, suggesting that induction of tolerance to crotoxin is likely a presynaptic event. PMID- 8474025 TI - Muscarinic m2 receptors in cerebellar granule cell cultures from rat: mechanism of short-term desensitization. AB - Cerebellar granule cell cultures of rat express only muscarinic m2 and m3 receptor subtypes and exhibit the pharmacological profile of muscarinic m2 receptors that couple to guanine nucleotide binding proteins to inhibit adenylyl cyclase. In vivo pretreatment with muscarinic agonists desensitizes the muscarinic m2 receptor with 50% complete desensitization within 15 to 20 min. After a 1-hr pretreatment with a maximal concentration of carbachol (short-term desensitization), m2 receptor responsiveness reappeared after a 1-hr treatment of cultures with atropine. However, after a 6-hr pretreatment with carbachol (long term desensitization), m2 receptor responsiveness did not reappear after 1-hr treatment with atropine. Short-term desensitization was homologous for the m2 receptor because treatment of cultures with carbachol did not alter gamma aminobutyric acidB receptor-mediated inhibition of adenylyl cyclase. Muscarinic m2 receptor desensitization was not mimicked by the addition of analogs of cyclic AMP, cyclic GMP or diacylglycerol to the cultures. The agonist-induced desensitization was not blocked by a cyclic AMP analog, 8-(4-chlorophenylthio) cyclic AMP. Pretreatment with antisense oligodeoxynucleotides against the mRNA encoding beta adrenergic receptor kinase attenuated the desensitization by carbachol (100 microM, 1 hr) of m2 receptors. Irreversible labeling of muscarinic m2 and m3 receptors with [3H]propylbenzilycholine mustard followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis produced a loss of the muscarinic m2 receptor (66-kDa protein), but not the muscarinic m3 receptor (92 kDa protein). We suspect that the short-term desensitization results from the phosphorylation of the muscarinic m2 receptor followed by loss of receptor from the plasma membrane. PMID- 8474026 TI - Characterization of a decrease in muscarinic m2 mRNA in cerebellar granule cells by carbachol. AB - Studies involving carbachol (100 microM) treatment of cerebellar granule cells for 1, 3, 6, 9, 12 and 24 hr show a decrease in the mRNA encoding for the muscarinic m2 receptor. The response was transient, decreasing m2 mRNA by 25 to 50% in 6 and 9 hr, respectively. The data presented in this work were quantified by ribonuclease protection assay, using a [32P]-cRNA probe corresponding to nucleotide +1138 to 1650 of the rat m2 muscarinic receptor. Because cerebellar granule cells express muscarinic m2 and m3 receptors, we tested whether the carbachol-mediated decrease in m2 mRNA resulted from a homologous or heterologous activation of muscarinic receptors. At a 1 microM concentration, methoctramine specifically blocked the muscarinic m2 receptor and reversed carbachol's action. These data suggested that carbachol acts via a possible homologous activation of muscarinic m2 receptors. The half-life of the receptor mRNA measured in the presence of actinomycin D with and without carbachol were similar. Because carbachol treatments decrease the steady-state levels of m2 mRNA without changing the half-life of the message, we suggest that a carbachol treatment induces a decrease in the transcription of the gene for the muscarinic m2 receptor. PMID- 8474027 TI - Thromboxane A2 stimulated signal transduction in vascular smooth muscle. AB - Thromboxane A2 (TXA2) is a potent, labile vasoconstrictor which stimulates vessel contraction through vascular smooth muscle TXA2 receptors differing from those in platelets. We studied TXA2-stimulated events in cultured adult rat aortic smooth muscle cells. The stable TXA2 mimetic (15S)-hydroxy-11 alpha,9 alpha (epoxymethano)prosta-5Z, 13E-dienoic acid (U46619) competed for TXA2 agonist binding to vascular smooth muscle cells with an IC50 of 10 +/- 1 nM. In fura-2 loaded cells, U46619 increased free cytosolic Ca++ concentration with an EC50 of 49 +/- 14 nM. The increase in free cytosolic Ca++ was rapid, transient and independent of extracellular Ca++ or Ca++ antagonists and thus was due to release from intracellular stores. U46619-mediated Ca++ release was temporally associated with phosphorylation of myosin light chains, increased accumulation of 1,4,5 inositol trisphosphate (EC50 = 32 +/- 4 nM) and cytoplasmic acidification from pH 7.06 +/- 0.01 to 7.00 +/- 0.02 (P = .02). Ca++ release was 53% attenuated by the phospholipase C inhibitor, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17 yl]amino]hexyl]-1H- pyrrole-2,5-dione. In rat aortic rings U46619 caused TXA2 receptor-mediated contractions (EC50 of 28 +/- 2 nM) which were not attenuated by removal of extracellular Ca++ from the superfusion buffer. Together, these results suggest that agonist occupation of TXA2 receptors produces vascular smooth muscle contraction through initial activation of phospholipase C with production of 1,4,5-inositol phosphate, release of intracellular calcium stores and phosphorylation of myosin light chains associated with cellular acidification, presumably via activation of Ca++ ATPase. PMID- 8474028 TI - Effects of a novel calcium antagonist, S-(+)-methyl-4,7-dihydro-3-isobutyl-6- methyl-4-(3-nitrophenyl)thieno[2,3-b]pyridine-5-carboxylate (S-312-d), on ischemic amino acid release and neuronal injury in stroke-prone spontaneously hypertensive rats. AB - The effects of a novel dihydrothienopyridine Ca antagonist S-(+)-methyl-4,7 dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)-thieno [2,3-b]pyridine-5 carboxylate (S-312-d), on the amount of amino acid release during cerebral ischemia and delayed neuronal death in the hippocampal CA1 region of stroke-prone spontaneously hypertensive rats were studied and compared with those of nimodipine. The released amino acids were measured by high-performance liquid chromatography after microdialysis. Cerebral ischemia was produced by occlusion of the bilateral common carotid arteries for 20 min. Intraduodenal administration of 0.3 mg/kg of S-312-d at 60 min before the carotid occlusion significantly decreased the ischemic release of glutamate and taurine, but did not influence their basal release. However, nimodipine did not inhibit the ischemic glutamate release even at a dose of 10 mg/kg. Similar peripheral hemodynamic effects were observed before and during bilateral carotid occlusion in groups treated with S 312-d or nimodipine. During the carotid occlusion, almost no cerebral blood flow was observed in either group. Therefore, the inhibitory effect of S-312-d on ischemic amino acid release probably arises from its potent direct action on neuronal cells. The neuronal cell densities of the CA1 subfield at 7 days after 20-min bilateral carotid occlusion significantly decreased in the vehicle-control group compared with the sham-operated group. Intraperitoneal administration of 0.1 mg/kg of S-312-d at 60 min before ischemia prevented the decrease of neuronal cell density compared with the vehicle control. These results show that S-312-d can offer marked neuronal protective effects against ischemic injury. PMID- 8474029 TI - Behavioral effects of pentobarbital, lorazepam, ethanol and chlorpromazine substitution in pentobarbital-dependent baboons. AB - Baboons were given continuous intragastric infusions of 100 mg/kg/day of pentobarbital before and during these experiments. The baboons responded under a fixed-ratio (FR) 30-response schedule of food presentation from 10:00 A.M. of one day to 8:00 A.M. of the next day. Terminating pentobarbital administration (i.e., substituting water for pentobarbital) from 8:00 A.M. of one day to 8:00 A.M. of the next day produced large decreases in the number of pellets earned. Repeated 24-h terminations of pentobarbital administration at 1-week intervals produced similar decreases in the pellets earned. In another experiment, the effects of terminating pentobarbital administration for several days were examined. The number of pellets earned decreased within 2 h of terminating pentobarbital administration was maximally suppressed during the first day, and recovered over 3 to 5 days. When different doses of pentobarbital were substituted for 24 h, the disruption of responding seen after pentobarbital termination was attenuated in a dose-dependent manner. In another experiment, the effects of substituting lorazepam, ethanol or chlorpromazine for pentobarbital for 24 h were examined. Lorazepam produced a dose-dependent attenuation of the effects of pentobarbital termination, whereas ethanol did not. Chlorpromazine did not attenuate the effects of pentobarbital termination in two of the three baboons tested, and produced erratic results in the third. PMID- 8474030 TI - Induction of cytochrome P450 2B1 in rat liver by the aromatase inhibitor aminoglutethimide. AB - Aminoglutethimide (AG) is an inhibitor of P450 aromatase and is in clinical use for the treatment of estrogen-dependent breast cancer in postmenopausal women. AG produces adrenal insufficiency by inhibition of the adrenal P450 cholesterol side chain cleavage enzyme, but a number of serious pharmacokinetic interactions have been reported between AG and coadministered drugs. The present study was undertaken in the rat to assess the modulatory capacity of AG toward P450 enzyme activities in vitro and in vivo and to identify the P450 subject to such effects. In vivo administration of AG produced a dose-related increase in activities attributable to the hepatic P450 enzyme 2B1. Thus, AG administration (25 and 50 mg/kg, i.p., on 3 consecutive days) resulted in 85 and 100% increases in testosterone 16 beta-hydroxylation and 3.3- and 7.4-fold increases in 7 pentylresorufin O-depentylation (both mediated by P450 2B1) in rat liver; at a dose of 5 mg/kg, no effect on these activities was noted. In addition, microsomes from rats administered high-dose AG catalyzed increased rates of androst-4-ene 3,17-dione 16 beta-hydroxylation (from 0.72 +/- 0.10 nmol/min/mg in control to 3.51 +/- 0.47 nmol/min/mg protein). These findings were confirmed by direct immunoquantification of P450 2B1 in hepatic microsomes, by which it was found that the content of the enzyme in control fractions (2.4 +/- 0.7 micrograms/mg microsomal protein) was increased 2.9- and 6.5-fold by the respective doses of AG. In contrast, there was no evidence for increases in two other similarly inducible proteins, P450 3A or P450 2C6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474031 TI - Mechanism of putrescine transport in human pulmonary artery endothelial cells. AB - Effective lung repair requires optimal replication of critical cell populations in the lung. Endogenous polyamines such as putrescine, spermidine and spermine play important roles in cell proliferation and differentiation, and may arise due to intracellular synthesis or transport into the cell. To determine the mechanism of polyamine transport in lung endothelial cells, the uptake of putrescine in human pulmonary artery endothelial cells was examined. Putrescine (7 nM) uptake into the cells approached equilibrium at 1 hr and was inhibited by methylglyoxal bis(guanylhydrazone). Kinetic studies revealed that uptake occurred via both a high- and low-affinity system. The effect of several amines (700 microM) on the 15-min uptake of putrescine was examined and a rank order of inhibition was determined: methylglyoxal bis(guanylhydrazone) > putrescine > spermine > spermidine > gentamicin > mepiperphenidol. alpha-Aminoisobutyric acid, a prototype system A amino acid, and tetraethylammonium, an organic cation, had no effect. N-ethylmaleimide inhibited transport 71%, whereas dinitrophenol did not. A reduction in temperature from 37 degrees C to 5 degrees C resulted in a 42% decrease in putrescine transport. Additionally, removing fetal bovine serum from the uptake medium reduced transport 38%. These data indicate that human pulmonary artery endothelial cells possess a specific transport system for polyamines. An improved understanding of this pathway in pulmonary endothelial cells may permit development of strategies to facilitate growth and repair of this critical cell population. PMID- 8474032 TI - Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: I. Effect of spiperone. AB - The i.v. administration of the 5-hydroxytryptamine (5-HT)1A antagonist spiperone (1 mg/kg) antagonized the suppressant effect of microiontophoretic applications of 5-HT and of the selective 5-HT1A agonist 8-OH-DPAT on the firing activity of the rat dorsal raphe 5-HT neurons. In contrast, the same dose of spiperone did not alter the responsiveness to microiontophoretic applications of 5-HT and 8-OH DPAT of pyramidal neurons in the CA3 region of the hippocampus, therefore indicating that spiperone does not act as a classical antagonist at these postsynaptic 5-HT1A receptors. After two daily injections of spiperone (5 mg/kg, i.p.) and a third one immediately before the experiment, the responsiveness of CA3 pyramidal neurons to 5-HT applied by microiontophoresis and to that released by the electrical stimulation of the ascending 5-HT pathway was markedly reduced. After 24, but not 12 or 48 h after a single injection of spiperone (5 mg/kg, i.p.), the responsiveness to exogenous and endogenous 5-HT was decreased. Smaller doses (1 and 2.5 mg/kg, i.p.) were ineffective. Haloperidol and ketanserin (5 mg/kg, i.p., 24 h before the experiment) were ineffective in blocking the responsiveness of CA3 pyramidal neurons to 5-HT, thereby demonstrating that the dopamine D2 and 5-HT2 properties of spiperone could not account for the attenuated responsiveness of the hippocampus neurons to 5-HT. Methiothepin (5 mg/kg, i.p., 24 h before recording), as for spiperone, antagonized the suppressant effect of 5-HT applied by microiontophoresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474033 TI - Morphine-induced alterations in thymocyte subpopulations of B6C3F1 mice. AB - Morphine has been reported to possess immunosuppressive actions in both in vitro as well as in vivo assays of immune function. Our work in female B6C3F1 mice, surgically implanted with a 75-mg time release morphine pellet, has confirmed previous reports of a rapid loss in the cellularity of the spleen and thymus. To evaluate the effect of morphine on the subpopulations of cells in the thymus, two color fluorescence flow cytometry studies were performed. Fluorescently conjugated monoclonal antibodies specific for the murine cell surface CD4 and CD8 markers were used to identify the four major subpopulations of thymocytes. These studies indicated that morphine pellet-implanted mice suffered a loss in each of the four thymocyte subpopulations in comparison to placebo-implanted mice. However, the loss (> 90%) in the important CD4+/CD8+ subpopulation of immature thymocytes greatly exceeded that which was observed for any other subpopulation. Kinetic studies of morphine's effect on the thymocyte subpopulations revealed that the maximal depletion of the CD4+/CD8+ cells occurs approximately 4 days after pellet implantation. Thymocyte cell populations recovered by 14 days, with an increase above placebo for the double positive cells. Naltrexone administration blocked thymic alterations, suggesting that these immunologic consequences of morphine may be mediated through an opiate receptor. Measurements in thymocytes from morphine pellet-implanted mice showed an increased level of DNA fragmentation, whereas in vitro exposure to morphine (1-100 microM) produced no such increases. This suggests morphine may be working indirectly to induce apoptosis of immature thymocytes. PMID- 8474034 TI - Respiratory control of sympathetic nerve activity during naloxone-precipitated morphine withdrawal in rats. AB - In this study, we describe and compare the changes in phrenic nerve discharge and vasomotor sympathetic output produced by 1) acute administration of morphine in naive rats and 2) naloxone-precipitated withdrawal in morphine-dependent rats. Lumbar or splanchnic sympathetic nerve discharge and phrenic nerve discharge were recorded along with mean arterial pressure and end-expiratory CO2 in vagotomized, urethane-anesthetized, paralyzed and artificially ventilated rats. Acute injection of morphine (1 and 5 mg/kg, i.v.) reduced resting mean arterial pressure, resting phrenic nerve discharge amplitude, the sympathetic baroreflex and the central respiratory drive of sympathetic nerve discharge. Subsequent administration of naloxone (1 mg/kg) reversed all cardiorespiratory effects of morphine and produced an overshoot, suggesting acute withdrawal. Morphine dependent rats displayed a prolonged central inspiratory phase and a higher threshold for apnea. Naloxone-induced withdrawal was associated with an increase of mean arterial pressure and phrenic nerve discharge amplitude and a large reduction in the inspiratory phase. Withdrawal produced three distinct effects on sympathetic nerve discharge: 1) sensitization of the baroreflex, 2) large increase in the central respiratory drive and 3) selective increase in a respiratory-independent component of the splanchnic sympathetic outflow. It is concluded that the increase in central respiratory drive is a significant component of the sympathoactivation associated with naloxone-induced withdrawal. PMID- 8474035 TI - Comparative action of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs on intestinal motility and nociception in rats. AB - Central (i.c.v.) effects of D-Tyr-D-Leu-[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(1DME)Y8Fa] and D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(3D)Y8Fa], synthetic analogs of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 on intestinal myoelectric activity and nociception were studied and compared to that of D-Ala2-Met5-enkephalinamide in rats. The duration of disruption of intestinal migrating myoelectric complexes, induced by p.o. administration of a test meal was significantly shortened (P < .01) by (1DME)Y8Fa and (3D)Y8Fa (8, 40 and 80 micrograms/kg) and D Ala2-Met5-enkephalinamide (40 and 80 micrograms/kg). The coadministration of any two of these drugs, at doses of nonmeasurable effect when given alone (2 micrograms/kg), has also reduced the duration (P < .01) of the postprandial intestinal motor profile. Both separate and combined effects of drugs were antagonized by naloxone (1 mg/kg s.c.). In contrast, in the tail-flick test, analgesia induced by D-Ala2-Met5-enkephalinamide (40 micrograms/kg i.c.v.) was blocked by (1DME)Y8Fa, (3D)Y8Fa (8 micrograms/kg) and naloxone (1 mg/kg s.c.). The coadministration of (1DME)Y8Fa and (3D)Y8Fa at doses of no proper effect when given alone (8 micrograms/kg) has significantly (P < .01) reduced the latency time. This effect was not blocked by naloxone (1 mg/kg s.c.). It is concluded that the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs, (1DME)Y8Fa and (3D)Y8Fa, when given i.c.v. exert effects similar to opiate agonists and antagonists on intestinal myoelectrical activity and on nociception, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474036 TI - Steady as a rock: does the steady state represent cognitive fossilization? AB - A study was performed in which data were obtained from adults and children with respect to their control of the inflexional morphology of the Spanish verbal system. Results indicate that adults have inferior knowledge of the paradigm compared to the children. Based on the types of errors committed, it is argued that linguistic knowledge may be more an ability to analogize correctly than to follow (unconscious) rules. Implications for GB (Government and Binding) theory and first and second language acquisition are discussed. PMID- 8474037 TI - [Role of MRI in the diagnosis of kidney cancer]. AB - The recent technical developments in magnetic resonance imaging (MRI) and the use of paramagnetic contrast media (gadolinium compounds) have considerably improved the performances of MRI for the detection and characterization of renal tumors. MRI does not have specific merits for the diagnosis of the typical form of cancer, nor for the detection of small kidney tumors, both being mainly based on computed tomography (CT). On the other hand, it can be used for the diagnosis of atypical forms of cancers (small, hypovascular, cystic or hemorrhagic cancers) which raise problems of differential diagnosis with some pseudotumoral lesions, complex cysts and benign tumors. Its complementarity to CT for the characterization of an atypical mass results from the signal information it provides, from a better contrast resolution, and from the possibility to make sections in all planes of space. Except for angiomyolipoma, which has a fatty content, there is no really specific MR criterion as present to evidence benign renal tumors. Concerning regional extension, CT remains the primary technique of choice, as it allows studying the limits of the tumor, the renal compartment ans its walls, the renal vein and the inferior vena cava, the neighboring organs and the contralateral kidney all together. Its findings allow defining the indications of MRI, which, as a complementary exploration, is often decisive to assess venous invasion. PMID- 8474038 TI - [Consumers of imaging tests]. PMID- 8474039 TI - [Surgery of hepatic metastases]. PMID- 8474040 TI - [MRI techniques applied to the diagnosis of hepatic tumors]. AB - We know that the contrast of MR images can be better than that of CT scans. In the spin echo mode, sequences with long TR and long TE provide great contrast, while, conversely, sequences with short TR and TE produce images with a greater anatomical fidelity. This dual performance, a notion that had never been expressed as explicitly in imaging, has led to distinguishing between the roles of MRI for detection and tissue characterization (diagnosis and nature). While the choice of an appropriate sequence for characterization has apparently been made immediately with a modulation of T2 weighting, the selection of a detection sequence is less easy. The number of parameters involved (signal-to-noise and contrast-to-noise ratios, spatial resolution, artifacts, imaging time) and the compromise arrangements needed to take them into account explain the lack of consensus as to the optimal sequence for detection. Instead of becoming simpler with time, the issue is increasingly complex, as now fast imaging has been developed in addition to conventional spin echo imaging, and may even supersede it. PMID- 8474041 TI - [Radiology and health economics in the USA]. PMID- 8474042 TI - [Neurocysticercosis of spinal manifestation. Apropos of a case]. AB - A case of spinal extramedullary cysticercosis with location in basal cisterns is reported. It was revealed by a severe sciatalgia and studied with MR imaging which is precious for the diagnosis and the follow-up. Cerebral cisternal arachnoiditis is the main problem in this racemose form where long medical treatment is necessary. PMID- 8474043 TI - [Pseudo-tumoral circumscribed myositis ossificans of the thoracic wall. Contribution of ultrasonography, x-ray computed tomography and MRI]. AB - The authors report the main clinical and radiographic aspects of a circumscribed myositis ossificans in a 5 year old child located in the thoracic wall, near the sternum, stimulating a malignant tumor. CT scan was more contributive than MRI, both for diagnosis and survey, because it shows better the progressive peripheral calcification typical of the lesion. PMID- 8474044 TI - [Mammographic aspects of Aschoff's proliferative centres]. AB - The pseudotumoral feature of radial scar cause considerable diagnostic problems mammographically and at the extemporaneous examination. From a series of 28 cases, the authors confront their experience with classical mammographic data and emphasize: the difficulty in analysing the central area of the radiating structure, the possibility of glandular retraction, the relationship between spicules and radiolucent linear structures. These radiological criterias do not allow us to affirm the diagnosis. Extraction with histological examination of the operatory fragment is the only attitude. PMID- 8474045 TI - [Role of x-ray computed tomography in the follow-up of the course of Hodgkin's disease]. AB - Fourteen files of patients having had Hodgkin's disease have been analyzed retrospectively to assess the justification of systematic surveillance after complete remission has been achieved. The data of successive CT exams, compared with the findings of clinical and biological studies performed on the same dates, confirm the primordial role of imaging, since computed tomography was predictive for 7 of 18 events (14 relapses and 4 second progressions). The occurrence of subphrenic recurrence in 3 cases for which the initial site was mediastinal leads to discussing the merits of a yearly thoraco-abdomino-pelvic examination during the two years following complete remission. PMID- 8474046 TI - Dental health among homebound elderly. AB - Currently, little is known about the oral health status, perceived oral health needs, or the extent of dental utilization among community-dwelling, functionally dependent elderly. The purpose of this study was to describe the dental health of functionally dependent elderly living at home and receiving community-based support services. The functional limitations experienced by these elderly living at home are comparable to functional limitations experienced by institutionalized elderly and these limitations impact on oral hygiene and access to dental care. Oral examinations and questionnaires were completed on 50 clients of an urban social service agency. Subjects had a mean of 8.8 teeth/person, with 44 percent completely edentulous. Two subgroups identified from the questionnaire--those who perceived themselves homebound (n = 30) and those who did not (n = 20), did not differ by age, gender, education level, or race. Respondents reported being homebound an average of 4.5 (+/- 2.9) years. The mean decayed, filled teeth for the perceived homebound group was 5.1, and 7.3 for the group that did not perceive themselves as homebound, with both groups averaging less than of one tooth/person with active root decay. Health care and social policy agendas must address the changing scope of oral health needs and limited access to dental care experienced by an aging population retaining more of their natural dentition. PMID- 8474047 TI - A half-century of community water fluoridation in the United States: review and commentary. AB - The nearly 50-year history of community water fluoridation is reviewed with the major emphasis on the benefits and safety of fluoridation. Other aspects of water fluoridation also described include the apparent reduction in measurable fluoridation benefits because of the abundance of other fluoride sources, the diffusion of fluoridation effects into fluoride-deficient communities, preeruptive and posteruptive effects, technical and cost aspects, sociopolitical and legal issues that affect the successful fluoridation of communities, and alternatives to community water fluoridation. The majority of studies have evaluated the effectiveness of water fluoridation on the permanent teeth of children, while there are fewer studies on deciduous teeth and in adults; the relationship between fluoride ingestion and bone health needs further clarification; the sociopolitical issues of fluoridation need to be better understood. PMID- 8474048 TI - Putting teeth in national health care reform. PMID- 8474050 TI - Resolution on community water fluoridation. PMID- 8474049 TI - Oral health care for the underserved in the 1990s: the HRSA perspective. PMID- 8474051 TI - Periodontal attachment loss in independently living older adults in Ontario, Canada. AB - This paper describes the periodontal disease experience of a community-dwelling population aged 50 years and older, living in four communities in Ontario, Canada. The periodontal status of this population was assessed using attachment loss and the extent and severity index. Attachment loss was measured at two sites on each tooth using a pressure-sensitive periodontal probe. Complete periodontal data were obtained on 624 subjects. The mean number of sites per subject was 37.9. In line with recent US studies, the diagnostic threshold for a diseased or previously diseased site was set at 2 mm of loss. The overall mean attachment loss was 2.95 mm, with 19.7 percent of subjects having an overall mean attachment loss of 4.00 mm or more. The proportion of sites examined with loss of attachment of 2 mm or more was 77 percent. The severity of disease, defined as the average distance between the base of the sulcus or pocket and a point 1.00 mm apical to the cemento-enamel junction in sites with loss of 2 mm or more was 2.44 mm. These data indicate that the extent and severity of disease in this population were greater than that reported by some recent studies in the US. Taken together, the results of these studies suggest that there is some variation in the periodontal disease experience of population subgroups across North America. PMID- 8474052 TI - Position statement on community water fluoridation. PMID- 8474053 TI - Interim policy statement on national health care reform. PMID- 8474054 TI - Autoantibodies to nuclear lamins and to intermediate filament proteins: natural, pathologic or pathogenic? PMID- 8474055 TI - The biology and clinical consequences of articular hypermobility. PMID- 8474056 TI - Hypothesis: cartilage catabolic cofactors in human arthritis. AB - Cartilage degradation in rheumatoid arthritis (RA) and osteoarthritis (OA) is commonly thought to be mediated by interleukin 1 (IL-1) and tumor necrosis factor (TNF). However, recent new evidence suggests that IL-1 and TNF on their own do not mediate all the cartilage changes seen in RA and OA. We propose that cartilage degradation is mediated by a complex network of cytokines, including IL 1, TNF and at least one cofactor present in synovial fluid. PMID- 8474057 TI - Effective treatment of mice with type II collagen induced arthritis with lethal irradiation and bone marrow transplantation. AB - We examined the effects of irradiation followed by bone marrow transplantation (BMT) on type II collagen induced arthritis (CIA) in mice. Either before or after the onset of arthritis, the mice were irradiated at levels lethal to cells, then given bone marrow cells from normal syngeneic or allogeneic mice. The BMT, especially allogeneic BMT, blocked the induction of CIA when administered before the onset of arthritis. When administered after CIA had begun, progression of the arthritis was significantly suppressed by allogeneic BMT. PMID- 8474058 TI - Methotrexate inhibits proliferation but not interleukin 1 stimulated secretory activities of cultured human synovial fibroblasts. AB - The effect of methotrexate (MTX) on proliferation and on interleukin 1 stimulated secretory activities of human synovial fibroblasts in culture was investigated. MTX caused a dose dependent inhibition of growth over the concentration range 0.07-2.2 microM with a half-maximal effect at 0.37 microM. INhibition was competitively relieved by coaddition of leucovorin. Cell growth was fully restored after MTX pretreatment of 24 h but not after 48 h, even on subsequent leucovorin addition. Cell viability was unaffected by MTX treatment. MTX had no effect on interleukin 1 stimulated production of prostaglandin E, hyaluronic acid and collagenase. Our results raise the possibility that one of the mechanisms contributing to the therapeutic effects of MTX in patients with rheumatoid arthritis may involve modulation of synovial fibroblast growth. PMID- 8474059 TI - Quantitative microfocal radiography detects changes in erosion area in patients with early rheumatoid arthritis treated with myocrisine. AB - Patients with early rheumatoid arthritis (RA) were randomly divided into those receiving gold early (n = 13) or 6 months later (n = 10). They were followed 6 monthly over 18 months. Mean erosion area in gold and delayed gold, measured from macroradiographs, was comparable at baseline and increased significantly over the first 6 months. In the second 6 months, gold showed no increase and delayed gold an insignificant increase. By the third 6 months both groups showed a decrease. On comparing the second 6 months of gold therapy in gold and delayed gold with a group of patients with RA of similar disease duration (n = 34) not receiving gold, a lower proportion (p < 0.005) had erosion area progression and a higher proportion (p < 0.001) erosion repair. PMID- 8474060 TI - Immunogenetics of familial rheumatoid arthritis: a study of 41 multicase families. AB - HLA haplotypes were studied in 41 unrelated families from North India with multiple cases of rheumatoid arthritis. Affected sibpairs shared parental HLA haplotypes more often than expected (chi 2 = 13.6) according to Mendelian segregation. Using the method of sibpair ratio, nonrandom segregation of parental haplotypes was observed among affected sibs. HLA-DR4 was observed in 70% of the probands while among DR4 negative probands, DR10 occurred more frequently. However no specific haplotypic association with the disease was observed in these families. PMID- 8474061 TI - Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. AB - Interleukin 6 (IL-6) appears to be a potential mediator of inflammation that may contribute to the pathogenesis of joint inflammation in RA. Anti-IL-6 monoclonal antibodies (Mab) may represent a new tool in RA treatment. Five patients with RA, after previous anti-CD4 therapy (B-F5) without antimouse immunization were included in our open pilot study. The anti-IL-6 Mab (B-E8, IgG1) was given intravenously (10 mg/day) for 10 consecutive days in hospital. No side effects were noted. Clinical and biological (C-reactive protein) improvement appeared during the treatment period. However improvement was transitory (mean: 2 months). Unexpectedly serum IL-6 levels increased in 4 patients with this treatment that seemed to have antiinflammatory effects. Further studies are required to evaluate the real benefit and the mode of action of this Mab. PMID- 8474062 TI - Is there an interaction between low doses of corticosteroids and methotrexate in patients with rheumatoid arthritis? A pharmacokinetic study in 33 patients. AB - A study of methotrexate (MTX) pharmacokinetics with and without prednisolone was performed in 33 patients with rheumatoid arthritis. Ten mg im MTX were given on Day 0; patients were divided into 3 groups of 11 persons: Group 1: no corticosteroid; Group 2: prednisolone 15 mg/day per os from D -3 on; Group 3: patients continuing longterm prednisolone treatment (15 mg/day). Groups 1 and 2 were randomized. MTX plasma concentrations were measured at T 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h using fluorescence polarization immunoassay (TDx Abbott). There was no difference between MTX pharmacokinetics of Groups 1 and 2. Area under the curve (AUC), Cmax and residual concentration at 24th h were higher, while total body and renal MTX clearances were lower in Group 3 vs Groups 1 and 2. Only the differences in AUC and total clearance were significant (p < 0.01 and p < 0.05). Tmax and terminal half-life did not differ. Our data suggest a possible influence of prednisolone on MTX pharmacokinetics in longstanding steroid treated patients. The pharmacological processes that might be involved are discussed. PMID- 8474063 TI - Dicyanogold (I) is a common human metabolite of different gold drugs. AB - Gold based drugs and their metabolites have been characterized using reversed phase, ion pairing chromatography with an inductively coupled plasma mass spectrometer as an element specific detector. For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking auranofin and in patients taking solganol. This represents the first identification of a specific gold metabolite in biological fluids taken from patients undergoing gold therapy and the first evidence that different gold drugs have common metabolites. PMID- 8474064 TI - Eosinophilia-myalgia syndrome in patients ingesting a single source of L tryptophan. AB - OBJECTIVE: To estimate the attack rate for eosinophilia-myalgia syndrome and to identify potential risk factors for illness among patients attending a New York City medical clinic, who purchased L-tryptophan containing products produced exclusively by Showa Denko K.K. METHODS: A case-control design was used. Cases and controls purchased L-tryptophan containing products at the medical clinic from July 1, 1989--December 1, 1989. All case-patients identified with illness onset during the study period were included. Controls were selected by a systematic sample of the 683 purchasers of L-tryptophan attending the same clinic. RESULTS: Twelve (2.2%) of an estimated 553 L-tryptophan users were case patients. Multivariate analysis suggested that lot 2 use (adjusted odds ratio [OR] = 35.9), concomitant use of chromium (adjusted OR = 12.3), and concomitant use of pyridoxine (adjusted OR = 5.8) were associated with the development of illness. Chemical analysis of tablets corresponding to the 3 Showa Denko K.K. lots ingested by study participants showed that lot 2 had the highest concentration of ethylidenebis (L-tryptophan), a proposed causative agent or marker for a causative agent in the eosinophilia-myalgia syndrome. CONCLUSIONS: Information from our study of persons exposed to implicated L-tryptophan supports the role for a contaminant as the causative agent in the eosinophilia-myalgia syndrome and identifies possible cofactors that deserve further study. PMID- 8474065 TI - Digital subtraction sialography of the parotid glands in primary Sjogren's syndrome. AB - Digital subtraction sialography of the parotid glands was performed in 34 patients with primary Sjogren's syndrome (SS) and 78 patients suspected of having primary SS in whom the diagnosis could be excluded (NON-SS). The following sialographic features were found more frequently in the patients with primary SS than in the NON-SS patients: a sparse overall branching pattern of the ducts, progressive widening and irregularity of the duct walls, disappearance of a homogeneous parenchyma blush and the occurrence of peripheral acinar dilations. The most discriminating findings between the 2 patient groups were the presence of acinar dilations and the disappearance of the homogeneous parenchyma blush. The sensitivity and specificity of the presence of acinar dilatations were 79 and 95%, respectively. Both the sensitivity and specificity of the presence of an irregular or absent parenchyma blush were 91%. The concurrent finding of acinar dilatations and an irregular or absent parenchyma blush had a sensitivity of 77% and a specificity of 95%. We conclude that digital subtraction sialography is a useful adjunctive diagnostic procedure for primary SS. PMID- 8474066 TI - Avascular necrosis of bone and antiphospholipid antibodies in systemic lupus erythematosus. AB - Of a total of 800 patients with systemic lupus erythematosus, 37 were found to have developed avascular necrosis of bone (4.6%). Routine radiological screening of all joints was not performed and these 37 represented symptomatic patients only. Twenty-seven of these were positive for antiphospholipid antibodies (aPL) (73%). Both aPL positive and aPL negative patients had received large doses of oral steroids. The frequency of vasculitis and livedo reticularis, as well as arterial thrombosis was higher in the aPL positive group, but this did not reach statistical significance, perhaps because of the small numbers of patients involved. Although the difference in the frequency of thrombocytopenia was more marked in the aPL positive group (p < 0.08), once again, this was not statistically significant at the 5% level. Since the prevalence of aPL positivity in the general lupus population is about 30-40%, the presence of the aPL may be associated with an increased tendency to develop avascular necrosis. This is supported by recent reports of avascular necrosis occurring in patients with primary antiphospholipid syndrome in the absence of previous steroid administration. PMID- 8474067 TI - Familial systemic lupus erythematosus characterized by digital ischemia. AB - We describe a family in which 3 members each developed systemic lupus erythematosus complicated by ischemic vasculopathy. The calendar years and patient ages of disease onset and the clinical courses were remarkably similar for all 3 patients, although their genotypes were not. The potential contributions of heredity and environment to the concordance of disease expression in this family are discussed. PMID- 8474068 TI - Lymphocytes from the site of disease suggest adenovirus is one cause of persistent or recurrent inflammatory arthritis. AB - The assessment of synovial lymphocyte reactivity to adenovirus antigen stimulation was undertaken in patients with persistent or recurrent inflammatory arthritis. The 3H-thymidine uptake procedure was employed, incorporating multiple microbiological antigens. Five patients were found with repeated maximal responses to adenovirus antigen; in one of these adenovirus nucleotide sequences were present in a synovial biopsy specimen. It is concluded that adenovirus may be one cause of persistent or recurrent inflammatory arthritis. PMID- 8474069 TI - 19th century spondyloarthropathy independent of socioeconomic status: lack of skeletal collection bias. AB - The representativeness of skeletal populations for characterization of the nature and frequency of disease could be questioned, as the bias of acquisition is often unclear. Examination of 2 proximate early 19th century cemetery populations, discordant for socioeconomic status, revealed indistinguishable character and frequency of spondyloarthropathy. Joint involvement, number and symmetry of joint erosions and fusion and skeletal distribution were indistinguishable in the 2 populations. It would appear that socioeconomic status does not bias skeletal populations, at least with respect to diseases for which no effective treatment was available. PMID- 8474070 TI - Decreased bone mineral density in HLA-B27 positive members of a family with osteogenesis imperfecta. AB - We describe a family in which several members had osteogenesis imperfecta (OI) and/or were positive for HLA-B27. The proband, who had ankylosing spondylitis and OI, had severe osteoporosis with fractures continuing to occur in the late teens. Bone mineral density measurements in 5 family members and the proband, revealed more severe osteoporosis in those with positive HLA-B27. PMID- 8474071 TI - Synovial type (group II) phospholipase A2 in cartilage. AB - Phospholipase A2 (PLA2) was produced in E. coli by a recombinant technique using a synthetic gene coding for PLA2 found in synovial fluid (SF) of patients suffering from rheumatoid arthritis (RA). Polyclonal antibodies were produced against the recombinant synovial type PLA2 (syn-PLA2) in a rabbit. The IgG fraction of the antiserum was isolated and the specificity was tested by immunoblotting. The antiserum detected a protein with an apparent molecular weight of 15 kDa in extracts of cartilage, but did not react with PLA2 isolated from human pancreas or ascitic fluid. In immunohistochemistry, the anti-syn-PLA2 antibody decorated chondrocytes and matrix of articular, laryngeal and auricular cartilage, but did not decorate synovial tissue or its contained inflammatory cells in RA or other human tissues tested (pancreas, liver, thyroid, tonsil, lung, nasal polyp, skin, placenta, myometrium, bone). The results show that syn PLA2 is present both in articular and extraarticular cartilage and support the view that PLA2 found in SF might originate from chondrocytes, and not from synovial lining or inflammatory cells. PMID- 8474072 TI - The relationship of obesity, fat distribution and osteoarthritis in women in the general population: the Chingford Study. AB - One thousand and three women aged 45-64 from the Chingford general population survey were studied cross sectionally to find the effect of quantity and distribution of body fat on the prevalence of radiologically confirmed osteoarthritis (OA) in the knee, carpometacarpal (CMC), distal interphalangeal (DIP), and proximal interphalangeal (PIP) joints. Obesity was classified as the upper tertile of body mass index (BMI kg/m2); the boundaries of the middle tertile were 23.4 and 26.4 kg/m2. The age adjusted odds ratio (OR) [and 95% confidence interval (CI)] of radiographic OA at the knee comparing the high and low tertile of BMI was 6.17 (3.26-11.71) and for bilateral knee radiographic OA was 17.99 (6.25-51.73). Comparing the middle and low tertile of BMI, the odds ratio for radiographic OA knee was 2.86 (1.44-5.68). For other joints the association between BMI and radiographic OA was less strong; the OR at CMC was 1.71 (1.05-2.78), at DIP was 1.52 (0.90-2.57), and at PIP was 1.23 (0.52-2.91). For all joints except PIP these OR increased if the diagnostic criteria included knee pain for at least a month, clinically evident swelling at the DIP or PIP, and pain or tenderness at the CMC. Recalled weight at age 20 years, or recalled maximum weight improved prediction of radiographic OA from current BMI, but measurement of fat distribution from circumference of waist, hip and thigh did not. Our results confirm that excess body weight is a powerful predictor of OA of the knee in middle aged women, and a modest predictor of DIP and CMC OA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474073 TI - Mechanisms of cartilage degradation in inflammatory arthritis: interaction between chondrocytes and immunoglobulin G. AB - A possible role for immune complexes in the degradation of cartilage (rheumatoid arthritis and antigen induced arthritis) has been modelled in vitro by studying interactions between cultured bovine chondrocytes and monomeric (M) or heat aggregated (HA) IgG. Concentrations of IgG used were within the range of values reported in the synovial fluids of rheumatoid joints. ELISA and rosetting assays revealed Fc receptor mediated binding of MIgG and HAIgG to chondrocytes that had been cultured, but not to freshly isolated cells. Both forms of IgG stimulated the production of metalloprotease, but only HAIgG boosted generation of superoxide anion and reduced proteoglycan synthesis. HAIgG also stimulated cells to produce immunoreactive interleukin 1 although no biological activity was apparent. It is concluded that the equivalent behavior of chondrocytes in vivo, triggered by immune complexes, could contribute or lead directly to matrix degradation. PMID- 8474074 TI - A comparative study of clinical signs in fibromyalgia/fibrositis syndrome, healthy and exercising subjects. AB - Pain threshold to pressure, skinfold tenderness, reactive skin hyperemia and tissue compliance were assessed in 60 subjects with fibromyalgia (FS) and 60 pain free [total control, (TC)] subjects comprising 30 normal controls (NC) and 30 exercising fit (FC) subjects. Pain threshold was significantly lower in FS than in TC (p = < 0.001) and NC (P = < 0.001). Skinfold tenderness was present in 95% of FS and 33% of the NC but was absent in all FC. In patients this tenderness was present both in painful and nonpainful sites, and when positive was significantly (P = < 0.001) more painful than in controls. Reactive skin hyperemia to pressure was significantly (p = < 0.001) increased in patients with FS compared to TC, but not to NC. Tissue compliance at trapezius, thoracic and lumbar locations was significantly (p = < 0.001) lower in patients than in any other controls. The fit subjects significantly differed from the unfit for pain threshold (p = < 0.001), reactive skin hyperemia (p = < 0.001), tissue compliance at right trapezius (p = < 0.001) and right thoracic (p = < 0.001) levels, and for the skinfold test (p = < 0.01). These 4 clinical signs could differentiate patients from controls with a mean accuracy of 86%. Our study indicates that there are clinical signs, apart from the tender points, which are abnormal in FS that appear to be useful as objective signs in the assessment of patients with FS, whether for diagnostic, therapeutic or research purposes. PMID- 8474075 TI - Performance of scored palpation, a point count, and dolorimetry in assessing unsuspected nonarticular tenderness. AB - Nonarticular tenderness was measured in 152 patients, 51 with rheumatoid arthritis, 50 with psoriatic arthritis, and 51 with human immunodeficiency virus infection. Three methods for assessing tenderness were used: a 14-site point count, scored tenderness at 10 sites (6 fibrositic and 4 control), and dolorimetry at the same 10 sites. The data from the 3 separate measures were converted into a common scale of standard deviation units for further analysis. There were strong correlations among the 3 measures. In particular, the scored tenderness at just 6 fibrositic sites provided as much information about the presence and severity of widespread tenderness as the other 2, more complex measures. At the interface between nontender and tender, the 2 methods based on palpation were significantly more sensitive to differences among individuals, than was dolorimetry. However, the palpation scales used did not evaluate different degrees of nontenderness. In 102 of the 152 subjects, there were 842 sites scored zero by palpation, and which showed widely different thresholds of tenderness by dolorimetry, significantly associated with diagnosis and sex. For screening and epidemiological purposes, scored tenderness at a limited number of accessible sites may be adequate and feasible, using the 18 point count of the new standard criteria as a gold standard for confirmation. For the assessment of generally acting factors affecting tenderness, dolorimetry is currently superior. PMID- 8474076 TI - Patient preferences for nonsteroidal antiinflammatory drug related gastrointestinal complications and their prophylaxis. AB - We conducted a pilot study examining the relative preferences for various nonsteroidal antiinflammatory drug associated adverse gastrointestinal events and misoprostol prophylaxis for these events. Thirty patients with rheumatoid arthritis volunteered to participate. A trained nurse interviewer administered the structured pretested interview. Respondents rated 18 hypothetical health states on a category rating scale with anchors at 0 (immediate death) and 100 (full health for life). Linear contrasts were created to test the null hypotheses of equal preferences, using t tests for correlated means. Our results suggest that respondents place a high value on the avoidance of (in order of decreasing importance) surgery, hospitalization, prophylaxis induced diarrhea and uncomplicated ulcer requiring outpatient treatment. The avoidance of ulcer symptoms (primarily dyspepsia) and the inconvenience of an additional medication taken 4 times daily (in the absence of diarrhea) appeared to be substantially less important from these patients' perspective. Further work is underway to confirm these preliminary findings. PMID- 8474077 TI - Assessment of nonarticular tenderness and prevalence of fibromyalgia in children. AB - Fibromyalgia syndrome (FS) is most common in midlife, but may be seen at any age. Its prevalence and assessment of tenderness in healthy children is not known. We assessed 338 healthy schoolchildren for tenderness thresholds and prevalence of FS. In all children a point count of 18 tender points (TP) was conducted by thumb palpation and tenderness of some of the TP sites as well as control point sites was further assessed using a Chatillon dolorimeter. All children and their parents were questioned about the presence of widespread pain or aching. Children were considered to have FS if they met the American College of Rheumatology (ACR) criteria for diagnosis of FS. Of the 338 children, 21 (6.2%) had FS. Thresholds of tenderness of 9 TP were 5.0 (1.2) (kg) [mean (standard deviation)] for boys vs 3.6 (0.8) (kg) for girls (p < 0.001). Thresholds of tenderness of the control point sites were 7.1 (1.4) (kg) for boys vs 5.5 (1.1) (kg) for girls (p < 0.001). Thresholds of tenderness of TP and control points in the children with FS were 2.5 (0.4) (kg) and 4.2 (0.5) (kg) vs 4.5 (1.2) (kg) and 6.6 (1.4) (kg) respectively in the children without FS (p < 0.001). We suggest that FS is common in the pediatric age group. Boys have lower tenderness than girls; children with FS have lower thresholds for tenderness both at control and TP compared to the subjects without FS. PMID- 8474078 TI - Joint hypermobility in pediatric practice--a review. AB - It has been well established that joint hypermobility may predispose children to the development of joint pain. Joint hypermobility represents an extreme variation of normal joint mobility with no underlying connective tissue diseases. Its prevalence among children varies from series to series. Evidence that there are differences between races and sexes exist. Joint hypermobility diminishes markedly throughout childhood and then more slowly during adult life. Although quantitative measurements in the assessment of joint hypermobility have been described, the criteria defined by Carter and Bird are preferred. Any subject who is able to perform 3 or more of the 5 maneuvers devised by these criteria was considered to have joint hypermobility. The mechanism in which joint symptoms develop is not well understood. Excessive motion or inappropriate physical activities that hyperextend the joint capsule, the ligaments and soft tissue constituent causing injury. These injuries are manifested by pain. The clinical features, prognosis and relevance to pediatric practice are discussed. PMID- 8474079 TI - Narcolepsy in systemic lupus erythematosus. AB - A 30-year-old woman, diagnosed as having systemic lupus erythematosus at the age of 18, presented with excessive sleepiness and cataplectic attacks. Sleep laboratory findings were consistent with narcolepsy. To the best of our knowledge an association between these 2 diseases has never been reported. The unrelated course of narcolepsy and lupus symptoms in our patient suggests a lack of common pathogenetic mechanisms and this association is more likely explained by genetic factors. PMID- 8474080 TI - Systemic lupus erythematosus and chronic intestinal pseudoobstruction. AB - We describe the first case of a patient with systemic lupus erythematosus in which clinical and radiological features, small bowel manometry and histological studies were consistent with the diagnosis of chronic intestinal pseudoobstruction. Our patient developed a fatal form of lupus with cerebral angiitis and tubulointerstitial lupus nephritis, with no sign of progressive systemic sclerosis or dermatopolymyositis. Postmortem examination confirmed the presence of an extensive fibrotic process in the muscularis layers, whereas the muscularis mucosae and the innervation of the digestive wall were spared. PMID- 8474081 TI - Diphosphonate bone scan in an unusual case of rhabdomyolysis: a report and literature review. AB - We describe a patient with bilobar pneumonia and acute renal failure, whose unusual skeletal muscle uptake on technetium methylenediphosphonate bone scan led to the diagnosis of rhabdomyolysis. The clinical and serologic findings were most consistent with Legionnaires' disease. Radioisotope scanning may occasionally be useful in the diagnosis and management of muscle disease, particularly myositis and rhabdomyolysis. PMID- 8474082 TI - Diffuse chondrolytic arthritis in sickle cell disease. AB - A young black man with sickle cell disease with recurrent painful vasoocclusive crises developed at 16 years of age a rapid disabling polyarticular chondrolysis leading to a bilateral hip arthroplasty in 1 year. Light microscopy showed erosion and chondrocyte loss with deep clones in the cartilage and congested vessels with extravasation of red blood cells and mononuclear cells in the synovium. Electron microscopy of the synovium disclosed partially occluded blood vessels and phagocytic cells containing red blood cell debris and crystalline hemoglobin-like material. These observations suggest a role for the phagocytic cells in the joint destruction. PMID- 8474083 TI - Late onset peripheral seronegative spondyloarthropathy: report of two additional cases. AB - Two more cases of late onset peripheral seronegative spondyloarthropathy (SpA) are reported. Like the patients reported by Dubost and Sauvezie, they had extensive pitting edema of the lower limbs, constitutional symptoms, elevated erythrocyte sedimentation rate and minimal involvement of the axial skeleton with marked signs of diffuse idiopathic skeletal hyperstosis. PMID- 8474084 TI - Multiple atypical bone involvement in sarcoidosis. AB - We describe a patient with right paratracheal and left hilar lymph nodes detected by chance on chest radiography that followed a spontaneous remission. However, a few months later she complained of multiple scalp nodules. Skull roentgenogram and computerized tomogram scan showed multiple osteolytic lesions with increased uptake in bone and gallium scans. Lytic lesions were also detected in her right mandibular bone and right clavicle. Noncaseating granulomas were demonstrated in skull and cervical lymph node biopsies. PMID- 8474085 TI - Aortic insufficiency and recurrent valve prosthesis dehiscence in MAGIC syndrome. AB - We describe a case of mouth and genital ulcers with inflamed cartilage (nasal and ear chondritis) (MAGIC syndrome). Our case was complicated by repeated aortic prosthetic valve dehiscence and femoral false aneurysm. The condition was resolved by treatment with corticosteroids and azathioprine. PMID- 8474086 TI - Drug allergy in Chinese patients with systemic lupus erythematosus. PMID- 8474087 TI - IgG antiphospholipid autoantibody in normal human sera is reactive against bromelain treated human erythrocytes. PMID- 8474088 TI - Responsiveness of outcome measures in rheumatoid arthritis trials. PMID- 8474089 TI - Role of erythropoietin in the anemia of chronic disorders. PMID- 8474090 TI - Outcome in rheumatoid arthritis. PMID- 8474091 TI - Sjogren's syndrome and acute suppurative parotitis. PMID- 8474092 TI - Juvenile systemic sclerosis. PMID- 8474093 TI - Magnetic resonance imaging is normal in the iliac crest pain syndrome. PMID- 8474094 TI - More on tender shins. PMID- 8474095 TI - Lack of antineutrophil cytoplasmic antibodies as marker for giant cell arteritis. PMID- 8474096 TI - On knee signs, a temperate response. PMID- 8474097 TI - Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56lck. AB - A study was undertaken to prepare inhibitors of the lymphocyte protein-tyrosine kinase p56lck. Using the known p56lck inhibitor 3,4-dihydroxy-alpha cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained mimetics in which the phenyl ring and vinyl side chain of the cinnamamide are locked into a coplanar orientation. Such planarity was rationalized to be an important determinant for binding within a putative flat, cleftlike catalytic cavity. Bicyclic analogues were prepared using the naphthalene, quinoline, isoquinoline, and 2-iminochromene ring systems and examined for their ability to inhibit autophosphorylation of immunopurified p56lck. The most potent analogues were methyl 7,8-dihydroxyisoquinoline-3 carboxylate (12) (IC50 = 0.2 microM) and 7,8-dihydroxyisoquinoline-3-carboxamide (13) (IC50 = 0.5 microM). Inhibition by 12 was not competitive with respect to ATP. These compounds may represent important new structural motifs for the development of p56lck inhibitors. PMID- 8474098 TI - Structure-activity relationships from molecular similarity matrices. AB - An alternative method for determining structure-activity correlations is presented. Ligand molecules are described using data matrices derived from the results of N by N (each molecule compared to every other) molecular similarity calculations. The matrices were analyzed using a neural network pattern recognition technique and partial least squares statistics, with the results obtained compared to those achieved using comparative molecular field analysis (CoMFA). The molecular series used in the study comprised 31 steroids. The resultant pattern recognition analysis showed clustering of compounds with high, intermediate, and low affinity into separate regions of the neuron output plots. The cross-validated correlation coefficients obtained from statistical analyses of the matrices against steroid binding data compared well with those achieved using CoMFA. These results show that data matrices derived from molecular similarity calculations can provide the basis for rapid elucidation of both qualitative and quantitative structure-activity relationships. PMID- 8474099 TI - Verapamil analogues with restricted molecular flexibility: synthesis and pharmacological evaluation of the four isomers of alpha-[1-[3-[N-[1- [2-(3,4 dimethoxyphenyl)ethyl]]-N-methylamino]cyclohexyl]]-alpha- isopropyl-3,4 dimethoxybenzene-acetonitrile. AB - The synthesis and pharmacological activities of the four isomeric racemates of alpha-[1-[3-[N-[1-[2-(3,4-dimethoxyphenyl)ethyl]]-N- methylamino]cyclohexyl]] alpha-isopropyl-3,4-dimethoxybenzene-acetoni trile are reported (2a-d). The compounds are verapamil analogues with restricted molecular flexibility designed to gather information on the active conformation(s) of the parent drug. The relative stereochemistry of the four racemates was established by X-ray crystallography and by 1H NMR spectroscopy; conformational analysis was supported by theoretical calculations. Negative inotropic and chronotropic activities were evaluated on guinea pig atria, while vasodilatory activity on smooth muscle was tested on guinea pig aortic strips. Binding studies on cat ventricles were performed using (-)-[N-methyl-3H]desmethoxyverapamil (D888) as a reference ligand. The results seem to support the hypothesis that cardiac depressant and vasorelaxant activities are due to different conformations of the verapamil molecule. PMID- 8474100 TI - Inactivation of monoamine oxidase B by analogues of the anticonvulsant agent milacemide (2-(n-pentylamino)acetamide). AB - Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine oxidase B (MAO B). The carboxylic acid was neither a substrate nor an inactivator. The trifluoromethyl compound was not soluble in buffer even when organic cosolvents were added, so it could not be tested. All of the other compounds were both substrates and time-dependent irreversible inactivators of MAO B. A plot of the logarithm of kcat/k(inact) (a measure of the efficiency of the inactivators) versus sigma I (Figure 1) shows a linear free energy relationship between the inactivator efficiency and the electron-withdrawing ability of the substituent. As the electron-withdrawing ability increases, the partition ratio decreases indicating that inactivation is becoming more efficient relative to substrate turnover to product. Milacemide was the least efficient of the compounds tested; the nitrile 2 was the most efficient. PMID- 8474101 TI - Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides. AB - A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor. PMID- 8474102 TI - Studies directed toward the design of orally active renin inhibitors. 2. Development of the efficacious, bioavailable renin inhibitor (2S)-2-benzyl-3- [[(1-methylpiperazin-4-yl)sulfonyl]propionyl]-3-thiazol-4-yl-L-alanine amide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (A-72517). AB - Employing a set of empirical guidelines for the design of well-absorbed renin inhibitors, we have followed two strategies to improve potency while maintaining bioavailability. One process involved incorporation of an extended N-terminal residue bearing a weakly basic substituent and is exemplified by compound 25. The other approach centered on the inclusion of an N-terminal sulfonamide and culminated in the discovery of inhibitor 32 (A-72517). Both 25 and 32 showed excellent bioavailability in the rat and ferret (> 25%) and, while subject to hepatic elimination in the monkey, were efficacious in this species. PMID- 8474103 TI - Potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme identified in rat lung. AB - Two structurally distinct series of potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme (ECE) activity identified in the rat lung have been developed. Pepstatin A, which potently inhibits the rat lung ECE, served as the basis for the first series. Alternatively, selected renin inhibitors containing the dihydroxyethylene moiety were shown to be inhibitors of rat lung activity. Subsequent modifications improved inhibition of the rat lung ECE while eliminating renin activity. Both series of ECE inhibitors demonstrated a range of selectivity over Cathepsin D. Water-solubilizing moieties were appended onto selected compounds to facilitate in vivo testing. Partial reduction of the pressor response to exogenously administered Big ET-1 was observed with selected rat lung ECE inhibitors. PMID- 8474104 TI - A trans-platinum complex showing higher antitumor activity than the cis congeners. PMID- 8474105 TI - Age at onset in Huntington's disease and methylation at D4S95. AB - Age at onset in Huntington's disease (HD) is variable and is influenced by parental sex, paternal age, and genetic background. Several recent models have tried to explain this variable expressivity by invoking parental imprinting and related aspects of epigenetic inheritance. Some of these mechanisms may result in variable DNA methylation at or near the HD gene. We show here that methylation at D4S95, a locus tightly linked to the HD gene, is highly variable. A comparison between patients with early onset HD, late onset HD, and normal controls showed no significant correlation between methylation and age at onset. However, we found a significant association of the age of the patient with demethylation at D4S95. Older persons tend to have lower levels of methylation at this locus. This observation is of interest with regard to studies that show an effect of paternal age, or more generally of 'ageing genes', on age at onset in HD. PMID- 8474106 TI - Alternative splicing of dystrophin mRNA complicates carrier determination: report of a DMD family. AB - Carrier determination is important for genetic counselling in DMD/BMD families. The detection of altered PCR amplified dystrophin mRNA fragments owing to deletions, insertions, or point mutations has increased the possibilities of carrier determination. However, problems may occur because of alternative splicing events. Here we present a family with a DMD patient characterised by a deletion of exons 45 to 54. At the mRNA level we detected a corresponding altered fragment which served for carrier determination. The mother and the sister of the patient showed the same altered dystrophin mRNA fragment as the patient and are therefore carriers. In the mother two additional altered dystrophin mRNA fragments were detectable, obviously resulting from alternative splicing in the normal allele. The grandmother and two other related females of the patient possess only the normal mRNA fragment. In a further female we detected an altered fragment owing to an mRNA deletion of exon 44. This fragment is created either by alternative splicing or a new mutation. Therefore, the carrier status of this female is still ambiguous indicating problems in carrier determination by the method of dystrophin mRNA analysis. PMID- 8474107 TI - Refining the genetic location of the gene for X linked hydrocephalus within Xq28. AB - The most common inherited form of hydrocephalus, X linked hydrocephalus (HSAS), is characterised by mental retardation, adducted thumbs, and spastic paraplegia. Genetic analysis has mapped the locus for HSAS to subchromosomal band Xq28 within a region of approximately 2 megabases of DNA. In order to refine the location of the disease gene we have conducted genetic linkage analysis with Xq28 marker loci in four additional HSAS families. A lod score of 4.26 with polymorphic marker DXS52 (St14) confirms the linkage of HSAS to Xq28. Identification of a recombination event between the HSAS gene and Xq28 loci F8C and DXS605 (2-19) reduces the size of the interval likely to contain the disease locus to about 1.5 megabases, the distance between DXS605 and DXS52. The locus for neural cell adhesion molecule, L1CAM, maps within this interval and therefore represents a candidate gene for HSAS. PMID- 8474108 TI - Hereditary anaemias in Portugal: epidemiology, public health significance, and control. AB - A countrywide prospective study aimed at establishing the prevalence of the haemoglobinopathy genes in the Portuguese population was carried out by screening 15,208 randomly selected blood samples from young males. This male based survey provided the opportunity of assessing simultaneously the prevalence of the red cell enzyme glucose-6-phosphate dehydrogenase (G6PD) deficiency, thus giving a picture of these important hereditary anaemias in Portugal. The results showed a low average frequency of beta thalassaemia (0.45%) and haemoglobin S (0.32%) carriers as well as G6PD deficiency (0.51%). However, these disorders are unevenly distributed throughout the country with a higher prevalence in some areas, mainly in the south. The relationship of this pattern of haemoglobinopathies to the known haplotypes linked to beta thalassaemia and sickle cell disease, relevant historical events, and local selective pressure was investigated. Hb D and Hb J are the commonest other structural variants. The implemented programme for control of these hereditary anaemias is described. PMID- 8474109 TI - Hypohidrotic ectodermal dysplasia, central nervous system malformation, and distinct facial features: confirmation of a distinct entity? AB - Internal hydrocephalus with partial hypoplasia of the cerebellum was observed in a severely mentally retarded boy who showed signs of ectodermal dysplasia. Diagnostic considerations are discussed. Reports of the triad mental retardation CNS malformation-ectodermal dysplasia are rare. In 1989 we reported a case with these signs that shows a striking facial similarity to the case presented here. PMID- 8474110 TI - Usher syndrome type I associated with bronchiectasis and immotile nasal cilia in two brothers. AB - Usher syndrome type I is an autosomal recessive disease characterised by congenital sensorineural deafness, involvement of the vestibular system, and progressive visual loss owing to retinitis pigmentosa. Here we report the association of this disease with bronchiectasis, chronic sinusitis, and reduced nasal mucociliary clearance in two sibs and we suggest Usher syndrome type I could be a primary ciliary disorder. PMID- 8474111 TI - Parental consanguinity in the blepharophimosis, heart defect, hypothyroidism, mental retardation syndrome (Young-Simpson syndrome). AB - In 1987 Young and Simpson reported a child with hypothyroidism, congenital heart disease, severe mental retardation, and striking facial dysmorphism. Two subsequent reports have described patients sharing some of the features of their case, although in both there were enough discordant features to make it uncertain that the same entity was being described. Here we present a female infant with virtually identical features to Young and Simpson's original case. Her Caucasian parents are first cousins, raising the possibility of autosomal recessive inheritance of this new syndrome. PMID- 8474112 TI - Aphasia, deafness, or mental retardation. PMID- 8474113 TI - Sex differences in the location of a spina bifida lesion. PMID- 8474114 TI - Immunotherapy of sepsis. PMID- 8474115 TI - Characterisation of a Helicobacter pylori phage (HP1). AB - The infection of two Helicobacter pylori strains with a phage-containing supernate of the lysogenic H. pylori strain IMMi 290/89 resulted in a lytic cycle and propagation of phage HP1. In negatively-stained preparations, the empty phage heads measured 55-60 nm in diameter and mature heads measured 50 nm. The flexible, striated phage tail was c. 170 nm in length and 9.5 nm in diameter. The phage showed a mean density of 1.40 g/cm3 in sucrose-density gradients and contained double-stranded DNA c. 22,000 bp in length. PMID- 8474116 TI - The role of thymine starvation in the expression of type IV plasmid-encoded trimethoprim-resistant dihydrofolate reductase. AB - Hyperproduction of the type IV plasmid-encoded dihydrofolate reductase was studied in Escherichia coli J62-2 (pUK1123). Hyperproduction of the enzyme was shown to occur not simply as a response to a given concentration of trimethoprim but also to the presence of thymidine in the medium. Before hyperproduction occurred the bacteria began to elongate and die, thus showing the symptoms of thymine starvation. Hyperproduction also required the presence of L-methionine, adenine and glycine, suggesting that the elevated production of the enzyme was a response to the ability of trimethoprim to starve the cell of thymine metabolites. PMID- 8474117 TI - The induction of trimethoprim resistance encoded by the type IV dihydrofolate reductase gene. AB - The effect of plasmid pUK1123, which confers low level resistance to trimethoprim when tested on solid minimal medium, but also no resistance when tested on IsoSensitest agar, was investigated in liquid media. The growth of Escherichia coli J62-2, harbouring pUK1123, was unaffected in liquid minimal medium containing trimethoprim 10 mg/L. However, in IsoSensitest broth, exposure to this drug concentration resulted in bacteriostasis. After an initial delay, resistance to trimethoprim was induced in IsoSensitest broth containing trimethoprim 10 mg/L, by the imposition of thymine starvation. This response was immediately reversible when trimethoprim was removed, confirming that resistance resulted from induction rather than selection of resistant mutants. PMID- 8474118 TI - Immunoglobulin-A detection and the investigation of clinical toxoplasmosis. AB - Current serological methods for the investigation of Toxoplasma gondii infection are unreliable for the diagnosis of congenital disease, reactivated infection associated with the acquired immune deficiency syndrome (AIDS), or the determination of the date of onset of infection. An enzyme-linked immunosorbent assay (ELISA) and an immunosorbent agglutination assay (ISAGA) were developed for the detection of toxoplasma-specific immunoglobulin-A (IgA) and used to investigate patients in these three categories. The IgA ISAGA and IgA ELISA were found to be reproducible and specific tests. The IgA ISAGA demonstrated enhanced sensitivity. Measurement of IgA in patients with toxoplasma-associated lymphadenopathy of known duration and AIDS patients with toxoplasma infection was of limited value. Detection of specific IgA by ISAGA was more sensitive than conventional methods for the diagnosis of congenital toxoplasmosis. We recommend the investigation of infant sera with IgA ISAGA. IgA estimation is not indicated in other clinical situations. PMID- 8474119 TI - Characteristics of an avirulent Campylobacter jejuni strain and its virulence enhanced variants. AB - The virulence of Campylobacter jejuni for 11-day-old chick embryos is associated with the ability to invade the chorio-allantoic membrane, to resist phagocytosis and to survive and proliferate in vivo. The pathogenicity of a well characterised avirulent C. jejuni strain was enhanced by passaging it intravenously and chorio allantoically through chick embryos. The resulting isogenic variants had greatly increased ability to survive in vivo. In this study, the morphological and cell surface characteristics of the avirulent parental strain were compared with those of the more virulent variants to determine whether pathogenicity was associated with one or more cell-surface constituents. Changes associated with the increased virulence of the two variants included alterations in cultural and cellular morphology, loss of flagella, expression of a new outer-membrane protein, alterations in cell-surface carbohydrates and decreases in cell-surface hydrophobicity. PMID- 8474120 TI - Maternal mortality in Mississippi: 1987-1991. AB - OBJECTIVE: To characterize the maternal mortality in the state of Mississippi for 1987-1991 and compare the maternal mortality from 1977-1986 with that of the last 5 years. STUDY DESIGN: Factors associated with maternal mortality were obtained from death certificates, replies to questionnaires, medical records, and autopsy reports. RESULTS: The maternal mortality rate in Mississippi for 1987-1991 (14.1/100,000) was not significantly different than for 1977-1986 (11.8/1000,000; P = 0.45). Over the last 5 years there was an increased incidence of direct obstetric deaths (50% vs 73%). During 1987-1991, toxemia as a cause of death for parturients decreased, while hemorrhage as a cause of maternal death increased. There was a rise in the incidence of patient related factors which were avoidable and which led to several deaths during 1987-1991. CONCLUSION: The state's maternal mortality rate remains stable. Improved patient and health care provider's education are necessary to further decrease the incidence of maternal death in Mississippi. PMID- 8474121 TI - Unsuspected arterial injury. PMID- 8474122 TI - Mississippi State Board of Medical Licensure annual report July 1, 1991 through June 30, 1992. PMID- 8474124 TI - Energetics of ionic contracture in rat-heart papillary muscles. AB - Energy dissipation and the bearing of tension during ionic contracture in myocardium may not result from one and the same process. To test this, comparative indirect and direct microcalorimetry determinations were made in non perfused tissue-cell preparations under optimal oxygenation conditions (right papillary muscles, high-pO2 superfusion, 30 degrees C) before, during and after exposure to low-Na, high-K solutions. Over a 15-min contracture plus 45-min recovery cycle, both heat production rate (E), and the indirectly determined heat production rate (EO2) which is oxygen uptake multiplied by the overall energetic equivalent of O2 for nutrient oxidations, were constantly larger than basal rates. The two 60-min time integrals of this increase in metabolic rate were equal [30.3 +/- 3.7 and 31.0 +/- 3.9 (SE) J/g muscle wet weight (n = 9) for E and EO2 respectively]. During contracture however, E exceeded EO2 by 24% (4.7 +/- 1.7 J/g), and during the recovery period EO2 exceeded E by 21% (5.4 +/- 2.6 J/g). Whereas oxidative recovery of the energy lost by the preparation during 15-min contractures was complete, after longer contractures recovery did not occur or was incomplete. In keeping with the now prevalent idea that ion--namely Ca- transport activities are maintained foremost among cellular ATP-dependent processes and consume significant amounts of energy, the present finding that in a 15-min ionic contracture myocardium incurs not only some, but the maximum oxygen debt still compatible with complete oxidative recovery suggests that contracture tension is maintained at low energy cost, essentially by slow-cycling or "rigor" bridges as in hypoxic contractures, whereas heat is mainly related to intracellular calcium homeostasis. PMID- 8474123 TI - Selective activation of cardiac angiotensinogen gene expression in post infarction ventricular remodeling in the rat. AB - Recent studies in both experimental animals and man have demonstrated the unique efficacy of converting enzyme inhibitors to prevent or attenuate ventricular remodeling after myocardial infarction. Concomitantly, evidence for a trophic role of the renin-angiotensin system (RAS), as well as for the existence of an intracardiac tissue-resident RAS, has been presented, raising the question whether altered regulation of this cardiac RAS may be associated with the process of ventricular remodeling. We conducted the present study to examine whether cardiac angiotensinogen gene expression is altered after myocardial infarction. Experiments were performed in rats 5 and 25 days after ligation of the left coronary artery or sham operation. Coronary artery ligation resulted in relative infarct sizes averaging 29% and 36% of total left ventricular mass at 5 and 25 days and in marked elevations of left ventricular end-diastolic pressure (LVEDP). Angiotensinogen mRNA levels, measured by solution hybridization assay and confirmed in a second, independent experimental group by RNAse protection assay, were significantly elevated in the non-infarcted portion of the left ventricle at 5 days after infarction when compared to the sham group (22.1 + 3.3 vs. 13.4 +/- 2.0 fg/microgram total RNA; ratio of densitometric absorbance for angiotensinogen/beta-actin: 0.356 +/- 0.041 vs. 0.156 +/- 0.02), and showed a significant correlation with infarct size (r = 0.93). At 25 days, angiotensinogen gene expression had returned to control values. Similarly, no significant differences in angiotensinogen mRNA levels between animals with and without infarction were found in other cardiac tissues (atria, right ventricle). Plasma renin activity was significantly increased over baseline in the infarct group at 5, but not at 25 days. Our results demonstrate that acute hemodynamic embarrassment early after LV infarction is associated with augmented angiotensinogen gene expression. The potential significance of this finding is discussed. PMID- 8474125 TI - The time course of myocardial glycogenolysis stimulated by glucagon. AB - The rate of glycogenolysis was measured using 13C-NMR in vivo in the rat heart following a glucagon bolus. Glycogen that had just been synthesized during a 50 min infusion of D-[1-13C]glucose and insulin was degraded at a rate of 2.5 mumol/min/g wet wt following a 250 micrograms bolus of glucagon. If a second 50 min infusion of unlabelled glucose followed the D-[-13C]glucose, the rate of mobilization of the labelled glycogen following glucagon was slower (0.52 mumol/min/g wet wt), indicating that the labeled glycogen was less accessible to the activated phosphorylase. Glycogen phosphorylase a (GPa) activity was measured in hearts freeze-clamped at intervals after the glucagon bolus. Activity rose rapidly to 6-fold basal and then returned to basal over 20-30 min (t1/2 decay of phosphorylase activity = 5.1 min). This time course paralleled the exponential fall in heart glycogen which followed glucagon (t1/2 = 4.3 min). Throughout the post-glucagon period the activity of phosphorylase exceeded the rate of glycogenolysis. These findings suggest that the activity of the phosphorylated form of glycogen phosphorylase (GPa) is an important but not the sole determinant of glycogen breakdown in the heart after a glucagon bolus. PMID- 8474126 TI - Alteration of cardiac collagen phenotypes in hypertensive hypertrophy: role of blood pressure. AB - The myocardium contains a fibrillar collagen matrix that consists primarily of type I and type III collagens. There is a marked alteration in the ratio and amount of collagen phenotypes in myocardial hypertrophy due to pressure overload. The purpose of the present study is (1) to study the effect of antihypertensive therapy on collagen phenotypes, if instituted before development of hypertension in spontaneously hypertensive rat (SHR), and continued into adult life and (2) to study the effects of dissociation of hypertension from hypertrophy, on collagen phenotypes in SHRs. The present study shows the effect of two antihypertensive drugs, hydralazine and captopril, on collagen phenotypes in SHRs. Both hydralazine and captopril effectively controlled blood pressure in SHRs, but only captopril regressed hypertrophy and corrected the altered distribution of myocardial collagen phenotypes I and III. Untreated SHRs had a collagen type I:III ratio of 10.19 +/- 0.27, compared with that of 6.41 +/- 0.30 in normotensive WKY (P < 0.001). Captopril-treated SHRs had a collagen type I:III ratio of 6.75 +/- 0.37, which did not differ significantly from that in normotensive WKY. Hydralazine-treated SHRs had a collagen I:III ratio of 10.07 +/ 0.39, which is similar to the ratio in untreated SHRs. In normotensive rats, neither captopril nor hydralazine significantly altered collagen content or the ratio of type I:III collagen. Thus captopril, an angiotensin converting enzyme inhibitor, not only regressed hypertrophy but also reversed the altered distribution of type I and type III collagen whereas hydralazine which effectively controlled blood pressure, did not regress hypertrophy and did not correct the altered distribution in collagen phenotypes. These studies suggest that alteration of collagen phenotypes during hypertensive hypertrophy is independent of blood pressure control and myocardial mass. PMID- 8474127 TI - Screening mammography: the other side of the coin. PMID- 8474128 TI - Managed care: Medicaid--a special case. PMID- 8474129 TI - A reformed health-care system: new paradigm centered on prevention. PMID- 8474130 TI - Delay between onset of chest pain and arrival to the coronary care unit among minority and disadvantaged patients. AB - Prehospital delay is an important cause of out-of-hospital coronary mortality. To determine the effects of decision time delay in a patient population comprised mainly of blacks and the underprivileged, 74 consecutive patients with acute chest pain necessitating admission to the coronary care unit in a large urban hospital were studied. Delay time from onset of chest pain to the decision to seek medical care was markedly prolonged in patients with myocardial infarction (n = 24; mean time: 11.3 +/- 18 hours) as well as in patients with chest pain who did not develop myocardial infarction (n = 50; mean time: 20.5 +/- 26 hours). In addition, transfer time from the emergency room to the coronary care unit was likewise unduly long (mean time: 4 +/- 3.8 and 4.1 +/- 6 hours for patients with and without myocardial infarction, respectively). This study documents a significant delay in the decision time among patients with low socioeconomic status, mostly inner-city blacks, and in the transfer time from emergency room to the critical care unit in a large public hospital. These findings must be taken into consideration when planning strategies to improve the health-care delivery system to blacks and the underprivileged and further lend support to the practice of initiating thrombolytic therapy in the emergency room. PMID- 8474131 TI - Imaging the hepatic lymphatics: experimental studies in swine. AB - Magnetic resonance (MR) imaging augmented with 3-D MR reconstruction provides an excellent display of the soft tissues and surface anatomy of the human body. The excellent anatomical detail of MR images makes this radiographic modality an ideal tool to teach anatomy to all health-care professionals. Previous studies of the lung and liver in swine revealed that the hepatic lymphatics communicated with the visceral pleural lymphatics via the so-called pulmonary ligament, which appears as a sheet of visceral pleura containing lymphatics and small blood vessels in the swine model. A review of the surgical operative reports at the UCLA School of Medicine revealed that the hepatic lymphatics are not connected or even ligated during hepatic resections and transplantations. Therefore, the authors hypothesized that the unattached lymphatics may be a cause of postoperative complications and that interruption of these important lymphatic pathways may specifically result in immediate ascites and right pleural effusions. Cannulation of the hepatic lymphatics is proposed as a method to reduce postoperative complications. The purpose of this research is to demonstrate the visual and radiographic display of the hepatic lymphatics in a swine model and to provide a means to teach anatomical-pathological correlation. PMID- 8474132 TI - A chronicle of racism. PMID- 8474133 TI - The effects of prenatal care utilization and maternal risk factors on pregnancy outcome between Mexican Americans and non-Hispanic whites. AB - This study evaluates the effects of prenatal care classification and levels of maternal risk status on pregnancy outcomes in Mexican Americans and non-Hispanic whites in Arizona. All live birth certificates from 1986 and 1987 were reviewed yielding a total population of 101,206 (26,827 Mexican Americans). The adequacy of prenatal care was evaluated based on an index that includes six prenatal care groups. Two levels of maternal risk status (low and high) were defined based on a series of maternal risk factors. Overall, Mexican Americans had a greater proportion of maternal risk factors and a greater proportion of mothers with inadequate or no prenatal care compared with non-Hispanic whites. Prematurity and macrosomia were more prevalent than low birthweight in Mexican Americans. Low risk status and adequate prenatal care regardless of ethnicity were found to be associated with a lower prevalence of low birthweight and preterm delivery. Whites, however, had a greater variation in the prevalence of low birthweight associated with changes in prenatal care utilization and maternal risk status compared with Mexican Americans. Finally, logistic regression analysis showed an independent effect of prenatal care, maternal risk status, maternal age, and maternal birthplace in predicting the overall low birthweight rate in Mexican Americans. The implications of these results are discussed relative to the usefulness of prenatal care as a health-care intervention in Mexican Americans. PMID- 8474134 TI - Shielding at the egress of a 23 mV linear accelerator. AB - Radiation shielding is required in radiotherapy accelerators to limit the dose equivalent rate from x-rays produced at the target in all directions except that of the useful forward directed beam. Calculations were made in terms of weekly workload of 50,000 cGy delivered to the isocenter per 5-day week, treating 25 patients per day at 400 cGy per patient. It is desirable to reduce the total exposure at the maze door below 30 Rem (0.30 Sv)/wk assuming full-time occupancy. The maze was designed to reduce the neutron dose to an acceptable level by slowing the neutrons to thermal velocities and then absorbing them in a low Z material in the egress. PMID- 8474135 TI - Distribution of lipoprotein phenotypes, cholesterol, and lipids in inner-city blacks. AB - Lipoprotein phenotypes total cholesterol, high-density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels were obtained from blood samples of 189 patients attending the Drew Hamilton Clinic in Central Harlem, New York, between 1987 and 1988. The study population ranged in age from 7 to 88 years; 135 of the patients were females and 54 were males. A difference in distribution of lipoprotein phenotypes was observed compared with the general population of the United States. Sixty-seven percent of blacks in this study were Type IIA compared with an estimated 10% of the general US population. Differences also were observed for blacks versus the general US population for Type IV (24% versus 45%), Type IIB (9% versus 40%), and Type V (0% versus 5%). Types I and III were rare in both groups (0% versus < 1%). The increased frequency of Type IIA among this predominantly black inner-city population may have implications for treatment strategies and prognostic value for predicting the risk of coronary heart disease. PMID- 8474136 TI - A review of the etiology of breast cancer. AB - It is important that physicians be aware of the current theories on the etiology of breast cancer. This article reviews some of the more probable etiologic factors of breast cancer. PMID- 8474137 TI - An abnormal gallbladder presenting as a huge, rounded photon-deficient area in radionuclide hepatobiliary imaging. AB - Tc-99m DISIDA hepatobiliary imaging was used to evaluate a hemophiliac patient presenting with symptoms of acute cholecystitis and gastrointestinal bleeding. There was nonvisualization of this abnormal gallbladder even on 6 1/2-hour delayed DISIDA images. Instead, a huge photon-deficient area was seen in the gallbladder fossa. Ultrasound and computed tomography findings were consistent with an enlarged gallbladder filled with blood. PMID- 8474138 TI - Listeria-associated pericarditis in an AIDS patient. AB - Listeria monocytogenes is a pathogenic, facultative intracellular gram-positive rod, generally seen in cell-mediated immunocompromised states. In acquired immunodeficiency syndrome (AIDS), it most commonly presents as bacteremia or meningitis. An association with pericarditis has not been described previously in this group of patients. This article describes a case of pericarditis secondary to listeriosis involving a focal pancarditis and necrosis of the A-V node with subsequent refractory ventricular tachyarrhythmias in an immunodeficient patient presenting with altered mental status. Infectious etiologies should be considered for "benign" appearing pericardial effusions in AIDS patients and the diagnosis of listeriosis excluded in the presence of "diphtheroid-like" organisms. PMID- 8474139 TI - Nightmares. AB - Nightmares are unpleasant or frightening dreams that occur sporadically in virtually all children. The peak incidence occurs between 3 and 6 years of age. Developmental, genetic, psychological, and organic factors have been identified as causes of nightmares. Nightmares usually occur in the middle of the night or in the early morning when rapid eye movement sleep is more common. The content of the nightmare almost always involves a specific danger to the child. On awakening, the child is fully alert, may be easily calmed or comforted, and can usually recall the details of the nightmare. Sporadic nightmares are common in children and require reassurance only. If nightmares are frequent and persistent, a psychological evaluation of the child and family is indicated. PMID- 8474140 TI - Molecular biology of vertebrate learning: is c-fos a new beginning? AB - An elevated expression of c-fos nuclear protooncogene (immediate early gene) has been shown repeatedly to correlate with long-term neuronal responses. This paper reviews recent data suggesting that neuronal plasticity, including learning and memory formation, may involve c-fos expression as well. On the basis of biological functions of the Fos protein, well known to be a component of a transcription factor, AP-1, (activator protein 1) a hypothesis suggesting a role of transcription factors in the integration of information during learning processes is proposed. PMID- 8474141 TI - Migrated fetal astrocytes modulate nerve growth factor expression in host nucleus gracilis of the medulla after grafting in third cervical hindlimb dorsal columns of the spinal cord. AB - Nerve growth factor (NGF) immunoreactivity in the nucleus gracilis of the medulla was quantitated for 90 days after aspiration of the C3 spinal hindlimb dorsal columns of 36 adult rats. Half the lesioned animals were a lesion-only group. The remaining lesioned animals received an immediate graft of two 1.0-mm pieces of 14 day gestation fetal rat cervical spinal cord (prelabeled with Phaseolus vulgaris leucoagglutinin) into the aspiration pocket (graft group). There were 3 normal controls. Groups of animals were analyzed at 7, 14, 21, 30, 60, and 90 days. At 90 days, NGF immunoreactivity was significantly elevated in the nucleus gracilis of lesion-only animals. This increase in NGF immunoreactivity was augmented in glial end-feet surrounding neurons and was also observed in the cytoplasm of astrocytes and some neurons. Previous experiments have shown that the cluster neurons of the nucleus gracilis undergo atrophy at this time with a concomitant decrease in hindlimb placement. NGF immunoreactivity (90 days) in grafted animals, however, was significantly less than in lesion-only animals (P < 0.05) but remained significantly elevated above control animals (P < 0.05). Unlike in lesion-only animals, there were no NGF positive neurons in the nucleus gracilis of grafted animals. Previous experiments have shown that astrocytes from fetal spinal cord grafts migrate to the nucleus gracilis, maintain cluster neuron cell size, and improve hindlimb placement at 90 days. The present data indicate that modulation of detrimental increases in NGF appeared to be a mechanism by which migrated fetal astrocytes can be used as a system for cell therapy. PMID- 8474142 TI - Oligodendrocyte proteoglycans: modulation by cell-substratum adhesion. AB - The signals that trigger the cytodifferentiation of oligodendrocytes (OLGs) are largely unknown. Using as a model system cultures of pure OLGs, we have shown that adhesion to a substratum initiates myelinogenesis (Yim SH, Szuchet S, Polak PE, J Biol Chem 261:11808-11815, 1986). It was of interest to investigate whether components such as proteoglycans (PGs) play any role in the biology of OLGs as it pertains to myelinogenesis. We set out to determine first, whether OLGs carry PGs; second, the nature of the association of these components with OLG plasma membrane; and third, if and how these PGs are modulated by OLG-substratum interaction. We compared the expression and characteristics of PGs extracted with different solvents from nonattached (B3.f) and attached (B3.fA) OLGs. B3.f and B3.fA OLG cultures were labeled with carrier-free 35SO4(2-) in serum-free medium. After removing excess label, OLGs were treated with heparin to extract susceptible components. Pellets were then exposed to 1% Triton X-100 plus 0.1 M NaCl and subsequently to 4 M guanidine-HCl plus 0.5 M NaCl. Solutions containing extracted material were characterized by size-exclusion chromatography, SDS-PAGE, and enzymatic degradation. Herein we report that (1) OLGs display [35S]PGs on their surface within 24 hr of substratum adhesion, and (2) these PGs can be operationally classified as peripheral and integral. We further show that the peripheral PGs are of high and intermediate size as assessed by size-exclusion chromatography and are segregated within the plasma membrane in such a way that the species with intermediate mass are extracted while OLGs remain adhered, whereas the high-molecular-weight species are only extracted after OLGs have been detached. Heparin also dislodges a number of sulfated proteins/Gps. Only a single class--high molecular weight--of integral PGs was identified; this PG requires guanidine-HCl for extraction. All PGs belong to the heparan sulfate class as evidenced by their degradation with heparitinase and their lack of susceptibility to chondroitinase ABC. The common theme of our findings is that these macromolecules have basal levels of expression in the nonadhered OLGs but undergo an adhesion-induced enhancement in their syntheses. We postulate that these PGs (1) play a role in OLG-substratum adhesion and hence myelinogenesis, and (2) may be determinants in establishing OLG polarity. Such polarization is the first overt sign of OLG functional differentiation and occurs prior to any morphological differentiation, e.g., extension of processes does not occur until 48 hr later when the plasma membrane is already polarized. PMID- 8474143 TI - A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina. AB - In the vertebrate retina, the retinal pigment epithelium (RPE) performs specific functions critical to the normal process of vision. Although some of these functions are well documented, molecular data are still scarce. Using the RPE specific monoclonal antibody RPE9, raised against human RPE cells, we have identified a novel 65 kD protein, conserved in mammals, birds, and frogs. This RPE-specific protein was found to be nonglycosylated. It was most effectively solubilized in the presence of detergent suggesting that it is associated with the RPE cell membranes. Its partitioning in the detergent phase of Triton X-114 and its solubilization in 0.75 M and 1.0 M KCl suggest that it interacts with the membrane either through a polypeptide anchor or charged amino acids. Cell fractionation by differential solubilization and differential centrifugation demonstrated that the protein was preferentially associated with the microsomal membrane fraction, where it is the major protein. Developmental expression of this 65 kD protein was examined in neonatal rats. Morphologically well differentiated RPE cells did not express the 65 kD protein at birth. However, expression was detectable at postnatal day 4, that is, one to two days before the photoreceptors develop their outer segments, suggesting that the expression of the 65 kD protein may be coordinated with other developmental events in the intact retina. This is further supported by the fact that RPE cells in confluent culture lose the expression of this protein within two weeks, while they maintain their characteristic epithelial morphology. Because of its specificity, its evolutionary conservation, and its timing of expression, it is possible that this protein may be involved in one of the key roles of RPE and as such is an important molecular marker for RPE differentiation. PMID- 8474144 TI - Localization of neprilysin (EC 3.4.24.11) mRNA in rat brain by in situ hybridization. AB - The distribution of the messenger RNA (mRNA) coding for neprilysin (EC 3.4.24.11) has been studied by in situ hybridization in the adult rat brain. A markedly heterogenous distribution among various brain regions was found. A strong signal was observed in the glomerular layer of the olfactory bulb, the olfactory tubercle, the caudate putamen, the habenular, anterior pretectal, interpeduncular, red, dorso tegmental, pontine, and vestibular nuclei, the mammillary bodies, the Purkinje cells, and the choroid plexus of the fourth ventricle. A large number of areas such as the cortex, the dentate gyrus, the hippocampus, the medial terminal nucleus of the accessory tract, the accumbens and the arcuate nuclei, the superior and inferior colliculi, and a few regions in the thalamus at the mesencephalic level exhibited a moderate or low signal of hybridization. The majority of these regions are also known to contain the neprilysin protein. On the other hand, the globus pallidus, the substantia nigra, and the central gray matter, which show a high or a moderate amount of neprilysin, did not contain any neprilysin mRNA. Comparison of the regional distribution of neprilysin mRNA with that of its translation product provides insight into neprilysin neuronal pathways in the central nervous system. PMID- 8474145 TI - Transient increases in neuropeptide Y-like immunoreactivity in dentate hilar neurons following fimbria/fornix transection. AB - Neurons containing neuropeptide Y (NPY) are numerous in those hippocampal regions that receive septal and monoaminergic afferents. To assess the role of these afferents in the expression of NPY in hippocampal neurons, the number and distribution of perikarya with NPY-like immunoreactivity (NPY-LI) was examined quantitatively in the dentate gyrus of adult male rats following unilateral transection of the right fimbria/fornix. In unlesioned rats, immunoperoxidase labeling for the antibody to NPY was detected mostly in fibers and only a few perikarya in the dentate gyrus. Following fornix transections, the number of detectable NPY-containing neurons in the hilus of the dentate gyrus ipsilateral to the lesion increased at 3 days post-lesion (dpl), peaked at 6 and 9 dpl, then returned to basal levels at 14 dpl and 1 and 6 months post-lesion. This elevation followed a rostral to caudal gradient. No apparent changes were found in the distribution of NPY-labeled neurons at any post-lesion interval studied. Moreover, no significant changes at any of the post-lesion times were found in the number or distribution of neurons with NPY-LI in the hilus of sham lesioned (i.e., ablations of the cortex and anterior hippocampal formation sparing the fornix) rats. The observed increases in the number of hippocampal neurons containing detectable NPY suggests that the cellular levels of this peptide are dependent on pathways travelling through the fornix. The rapid and transient increases in NPY are not due exclusively to changes in cholinergic pathways but may involve changes in other pathways within the fornix or even indirect neurotrophic effects. PMID- 8474146 TI - Perinatal morphine treatment inhibits pruning effect and regeneration of serotoninergic pathways following neonatal 5,7-HT lesions. AB - Lesion of the serotoninergic system in neonate rats is an ideal model for assessing the activity of chemical substances capable of affecting neuronal plasticity and regeneration (Jonsson et al., Dev Brain Res 16: 171-180, 1984). Treatment of newborn rats within 6 hr from birth with the selective neurotoxin 5,7-dihydroxytryptamine causes degeneration of the most distal serotoninergic axons. In our experimental conditions we have observed that after such neurotoxic treatment there is spinal cord denervation, which is particularly remarkable in the lumbar segment. This degenerative event is followed by gradual regeneration of the lesioned axons, with good reinnervation of the entire cord within 8 weeks. The degeneration-regeneration process is correlated with a transient hyperinnervation of the pons-medulla and hypothalamus by the short collaterals (pruning effect), as evidenced by increased serotonin content. Perinatal morphine exposure markedly impairs serotonin regeneration in the spinal cord. In addition, opiate treated rats are more susceptible to lesions, as shown by the neurotoxin induced denervation of the cortex, pons-medulla, and hypothalamus, which does not occur in lesioned controls. Therefore, our observations suggest that perinatal exposure to morphine affects the plasticity and regeneration of the developing serotoninergic system by increasing its susceptibility to neurotoxic lesions and reducing its regenerative capacity. PMID- 8474147 TI - Phospholipid and phospholipid fatty acid composition of mixed murine spinal cord neuronal cultures. AB - The phospholipid and phospholipid fatty acid compositions of mixed murine spinal cord neuronal cultures are reported. The phospholipid composition was primarily comprised of ethanolamine glycerophospholipids (44.8%) and choline glycerophospholipids (43.5%). Plasmalogens made up 29.1% of the ethanolamine glycerophospholipids (13.0% of the total phospholipids) and 4.5% of the choline glycerophospholipids (1.9% of the total phospholipids). Other phospholipids ranged from 2.9% for sphingomyelin to 1.0% for phosphatidylinositol 4-phosphate. The fatty acid compositions of the ethanolamine glycerophospholipids, choline glycerophospholipids, phosphatidylserine, and phosphatidylinositol were also determined. The choline glycerophospholipids were the most saturated and contained the smallest amount of polyunsaturated fatty acids. The ethanolamine glycerophospholipids were the most unsaturated and contained the highest amount of polyunsaturated fatty acids. The phospholipids contained minimal amounts of 20:3 n-9 (Mead acid) and are not considered polyunsaturated fatty acid deficient. Thus, for the mixed neuronal spinal cord cultures, the phospholipid fatty acid compositions were not polyunsaturated fatty acid deficient and contained a large amount of polyenoic fatty acids of both the n-3 and n-6 series. PMID- 8474148 TI - The protective effect of 4-hydroxy-2-methyl-N-[2-(tetrazol-5-yl)- phenyl]-2H-1, 2 benzothiazine-3-carboxamide-1, 1-dioxide monosodium salt (HX-1920) on cisplatin induced toxicity in rats. AB - The protective effect of 4-hydroxy-2-methyl-N-[2-(tetrazol-5-yl)-phenyl]-2H-1, 2 benzothiazine-3-carboxamide-1, 1-dioxide monosodium salt (HX-1920) on the nephrotoxicity of cisplatin was studied in rats. Effects of HX-1920 on antitumor activity and emesis induced by cisplatin were also examined using mice and ferrets, respectively. All 10 rats injected with both HX-1920 and LD50 of cisplatin survived for 14 days. After 24 hr, co-administration of HX-1920 significantly increased the urinary excretion of cisplatin in rats. HX-1920 also significantly inhibited the cisplatin-induced elevation of urinary N-acetyl-beta D-glucosaminidase, blood urea nitrogen and plasma creatinine concentrations in rats. HX-1920 had no effect on the number of white blood cell. HX-1920 tended to reduce the emesis induced by cisplatin in ferrets. Furthermore, there was no difference in the survival curve between the cisplatin group and the HX-1920 plus cisplatin group in mice inoculated with P 388 leukemia cells. Thus, HX-1920 did not modify the antitumor activity of cisplatin. These results suggest that HX 1920 has a protective effect on the nephrotoxicity of cisplatin without inhibiting its antitumor activity. PMID- 8474149 TI - Effects of prenatal aluminum treatment on development and behavior in the rat. AB - Developmental and behavioral effects of aluminum administration were studied in THA rats. To three groups of pregnant rats were administered single dose of 0, 900 or 1,800 mg/kg of aluminum chloride on the day 15 of gestation by gavage. Significant differences were observed between the aluminum treated offspring and controls in terms of body weight, timing of pinna detachment and eye opening, and appearances of auditory startle. Slower learning acquisition was observed in treated groups. The longer latency and more rearings in the open field test were observed in 1,800 mg/kg treated females. These results suggest that single dose of aluminum chloride during prenatal period affects the development and behavior in rats. PMID- 8474150 TI - Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert butylphenol) in rats. 2. Uncoupling effect on oxidative phosphorylation of liver mitochondria. AB - Effects of 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) on hepatic mitochondrial oxidative phosphorylation in vitro, and on hepatic peroxisomal enzymes activities and microsomal mixed-function oxidase activities were studied. 1. A low concentration of MBEBP, less than 50 microM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100 microM, acted as a respiratory inhibitor. Therefore, MBEBP was found to act as an uncoupler of oxidative phosphorylation in rat liver mitochondria. 2. MBEBP significantly decreased peroxisomal enzymes, cyanide insensitive palmitoyl-CoA oxidizing activity and catalase activity in the livers of rats fed 0.2, 1.0 or 5.0% MBEBP for 4 weeks. 3. In microsomal enzyme assay, NADPH cytochrome c reductase activity was significantly increased, however, cytochrome P-450, cytochrome b5 levels, aminopyrine N-demethylase and benzo [a] pyrene hydroxylase activities were not significantly increased in the livers of rats fed 1.0 or 5.0% MBEBP for 4 weeks. The weight loss and the decrease of serum triglyceride level observed in the MBEBP-treated rats seemed to be caused by its uncoupling effects, which might also be the cause of the testicular damage induced by MBEBP. PMID- 8474151 TI - Hormonal disregulation mechanism in the rat thyroid tumor induced by diniconazole. AB - To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2,4-dichlorophenyl)- 4,4-dimethyl 2-(1,2,4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1,000, or 2,000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T4) and free T4 levels at and above 1,000 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2,000 ppm concurrently with liver weight and hepatic UDP glucuronyltransferase (UDP-GT) increases at and above 1,000 ppm. No changes were observed in serum triiodothyronine (T3) and free T3 levels. Increase in thyroid uptake of 125I and organification of 125I in the thyroid at 2,000 ppm and thyroid follicular cell hyperplasia at and above 1,000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T4 and free T4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased 125I uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans. PMID- 8474152 TI - Isolation and genetic characterization of ethanol-resistant reovirus mutants. AB - To better understand the mechanism(s) by which viruses respond to chemical or physical treatments, we isolated a series of mutant strains of reovirus type 3 Dearing that exhibit increased ethanol resistance. Following exposure to 33% ethanol for 20 min, the parental strain exhibited a 5 log10 decrease in infectivity. The mutant strains, however, exhibited a 2 to 3 log10 decrease in titer following identical treatment. Through the use of reassortant viruses, we mapped this increased ethanol resistance mutation to the M2 gene segment, which encodes a major outer capsid protein, mu1C. Sequence analysis of mutant M2 genes revealed that six of seven unique mutants possessed single-point mutations in this gene. In addition, the change in six of seven mutants caused a predicted amino acid change in a 35-amino-acid region of the gene product between amino acids 425 and 459. The identification of ethanol resistance mutations within a discrete region of this outer capsid protein identifies that portion of the protein as important in reovirus stability. The presence of viral particles possessing altered stability also suggests that subpopulations of viruses may possess altered environmental stability, which, in turn, could affect viral transmission. PMID- 8474153 TI - Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant. AB - Simian immunodeficiency virus (SIV) induces an immunodeficiency syndrome similar to human AIDS. Although the disease course of SIV-induced immunodeficiency is generally measured in months to years, a disease syndrome that results in death in 5 to 14 days has been described in pig-tailed macaques infected with the SIVsmmPBj (PBj) strain. The purpose of this study was to derive an acutely lethal PBj molecular clone in order to study viral genes involved in pathogenesis. Six infectious molecular clones were generated; acutely fatal disease was induced by experimental inoculation of pig-tailed macaques with virus stocks derived from either of two clones, PBj6.6 or PBj14.6. Molecular chimeras were constructed by exchange of regions of the genome of PBj6.6 and a nonlethal, related clone, SIVsmH4. Only a chimera expressing the PBj genome under the control of a SIVsmH4 long terminal repeat induced death soon after inoculation. These studies suggest that multiple viral genes of PBj are critical for development of acute disease. More specifically, the env gene but not the long terminal repeat PBj was required for acute disease induction; however env must act in concert with another gene(s) of the PBj genome. PMID- 8474154 TI - Sequence and characterization of the major early phosphoprotein p32 of African swine fever virus. AB - The gene encoding protein p32, the most abundant and immunogenic protein induced by African swine fever virus at early times of infection, has been mapped in the EcoRI C' fragment of the genome of the Vero cell-adapted virus strain BA71V. Sequencing analysis has shown the existence of an open reading frame, named C'204L, encoding 204 amino acids. The protein is phosphorylated in serine residues located in the 115 N-terminal amino acids and was phosphorylated when expressed in cells infected with a vaccinia virus recombinant. Protein p32 is not glycosylated in spite of the presence of two putative N-glycosylation sites in the deduced amino acid sequence of the polypeptide. Immunofluorescence experiments have shown that the protein is localized in the cytoplasm of infected cells and not in the plasma membrane. In addition, the protein has been found in the soluble fraction and not in microsomes from BA71V-infected Vero cells. Low levels of the protein have been detected in the medium from infected swine macrophages, which probably corresponds to nonspecific release of cytoplasmic proteins. The protein encoded by other virus isolates shows different electrophoretic mobilities, indicating variability of p32. PMID- 8474155 TI - Dominant negative mutants of human T-cell leukemia virus type I Rex and human immunodeficiency virus type 1 Rev fail to multimerize in vivo. AB - Human T-cell leukemia virus type I (HTLV-I) Rex and human immunodeficiency virus type 1 (HIV-1) Rev are essential gene products required for the replication of these two pathogenic human retroviruses. Both Rex and Rev act at a posttranscriptional level by binding to highly structured RNA-response elements, the Rex-response element in HTLV-I and the Rev-response element in HIV-1. Using a sensitive in vivo assay of protein-protein interaction, we now demonstrate that the HTLV-I Rex and HIV-1 Rev proteins readily form homomultimeric complexes in the absence of their cognate RNA-response elements yet fail to form heteromultimeric complexes with each other. Dominant negative mutations have been identified in both the rex and rev genes which presumably specify a critical activation or effector domain in each of these viral transactivators. Surprisingly, these dominant negative mutants of Rex and Rev fail to interact in vivo. These findings raise the possibility that the binding of nonfunctional monomers rather than functional multimers underlies the transdominant phenotype of these Rex and Rev mutants. Further, it seems likely that the assembly of functional and stable multimers of Rex and Rev in vivo may depend not only on the intrinsic multimerization domains of these proteins but also on the binding of a bridging cellular cofactor to the related activation domains present in each viral transactivator. PMID- 8474156 TI - A poxvirus-encoded uracil DNA glycosylase is essential for virus viability. AB - Infection of cultured mammalian cells with the Leporipoxvirus Shope fibroma virus (SFV) causes the induction of a novel uracil DNA glycosylase activity in the cytoplasms of the infected cells. The induction of this activity, early in infection, correlates with the early expression of the SFV BamHI D6R open reading frame which possesses significant protein sequence similarity to eukaryotic and prokaryotic uracil DNA glycosylases. The SFV BamHI D6R open reading frame and the homologous HindIII D4R open reading frame from the Orthopoxvirus vaccinia virus were cloned under the regulation of a phage T7 promoter and expressed in Escherichia coli as insoluble high-molecular-weight aggregates. During electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, the E. coli expressed proteins migrate with an apparent molecular mass of 25 kDa. The insoluble protein aggregate generated by expression in E. coli was solubilized in urea and, following a subsequent refolding step, displayed the ability to excise uracil residues from double-stranded plasmid DNA substrates, with the subsequent formation of apyrimidinic sites. The viral enzyme, like all other characterized uracil DNA glycosylases, is active in the presence of high concentrations of EDTA, is substrate inhibited by uracil, and does not display any endonuclease activity. Attempts to inactivate the HindIII D4R gene of vaccinia virus by targeted insertion of a dominant xanthine-guanine phosphoribosyltransferase selection marker or direct insertion of a frame-shifted oligonucleotide were uniformly unsuccessful demonstrating that, unlike the uracil DNA glycosylase described for herpesviruses, the poxvirus enzyme is essential for virus viability. PMID- 8474157 TI - Sequence, transcriptional mapping, and overexpression of p47, a baculovirus gene regulating late gene expression. AB - A 2.8-kb region of the Autographa californica nuclear polyhedrosis virus genome was sequenced and found to contain an open reading frame (p47) which was capable of rescuing a previously characterized temperature-sensitive mutant, ts317 (S. Partington, H. Yu, A. Lu, and E. B. Carstens, Virology 157:91-102, 1990). Transcriptional mapping demonstrated that an early 4.2-kb RNA encoded the p47 open reading frame and probably overlapped the 39K delayed-early gene. The p47 open reading frame was cloned behind the polyhedrin promoter in a baculovirus transfer plasmid, which was then used to prepare a recombinant baculovirus overexpressing the p47 polypeptide. The overexpressed polypeptide was used to prepare p47-specific monoclonal antibodies. These antibodies detected a polypeptide of 47 kDa in A. californica nuclear polyhedrosis virus-infected cells, demonstrating that p47 is expressed as an authentic viral product. The p47 gene product was localized to the nucleus of infected cells, supporting the hypothesis that it is involved in regulating viral transcription at late times postinfection. PMID- 8474158 TI - Functional motifs of delta antigen essential for RNA binding and replication of hepatitis delta virus. AB - The functions of delta antigens (HDAgs) in the replication of hepatitis delta virus (HDV) have been identified previously. The small HDAg acts as a transactivator, whereas the large HDAg has a negative effect on replication. To understand the molecular mechanisms involved in the control of HDV replication, we have established a replication system in Huh-7 cells by cotransfecting a monomeric cDNA genome of HDV and a plasmid encoding the small HDAg. We demonstrate that a leucine repeat in the middle domain of the small HDAg is involved in binding to the HDV genome and transactivation of HDV replication. When the leucine repeat was disrupted by a substitution of valine for leucine at position 115, both RNA-binding and transactivation activity of the small HDAg were abolished. In contrast, the binding and transactivation activities were not affected when Leu-37 and Leu-44 of the small HDAg were replaced by valines. In addition, small and large HDAgs can interact with each other to form protein complexes in vitro. The complex formation that may lead to the trans-dominant negative regulation of large HDAg in HDV replication is mediated by a cryptic signal located between amino acid residues 35 and 65 other than the putative N terminal leucine zipper motif. Furthermore, an extra 21-amino-acid extension near the N terminus converts the small HDAg into a pseudo-large HDAg with negative regulation activity of HDV replication even though the extreme C-terminal residue is unchanged. PMID- 8474159 TI - Basic amino acids flanking the zinc finger of Moloney murine leukemia virus nucleocapsid protein NCp10 are critical for virus infectivity. AB - Nucleocapsid (NC) protein NCp10 of Moloney murine leukemia virus is encoded by the 3' domain of gag and contains a zinc finger surrounded by basic amino acids. During virion assembly, NC protein is necessary for core formation and the NC zinc finger is required for the packaging of the genomic RNA dimer. In vitro NCp10 has RNA-binding and -annealing activities critical for virus infectivity, since NCp10 promotes dimerization of viral RNA containing the Psi packaging element and annealing of replication primer tRNA(Pro) to the initiation site of reverse transcription (primer-binding site). To investigate the role of the basic amino acids flanking the NCp10 zinc finger, neutral residues were substituted for the basic amino acids and the effects of these mutations in vivo on virus assembly and infectivity and in vitro on the RNA-annealing activity of NCp10 were analyzed. Here we report that the substitution of 1 or 2 neutral amino acids for the basic residues did not impair the production of mature virions but that infectivity was either moderately or strongly attenuated. When more than 2 basic residues were replaced by neutral amino acids, viruses were poorly infectious because of a severe defect in genomic RNA dimer packaging and initiation of reverse transcription. In vitro NCp10-derived peptides with similar mutations were chemically synthesized and were found to be either fully or partially active or completely inactive. These data indicate that the basic residues flanking the zinc finger of NCp10 are required for the production of infectious Moloney murine leukemia virus virions. PMID- 8474160 TI - Site-directed mutations in the Sindbis virus E2 glycoprotein identify palmitoylation sites and affect virus budding. AB - The assembly and budding of Sindbis virus, a prototypic member of the alphavirus subgroup in the family Togaviridae, requires a specific interaction between the nucleocapsid core and the membrane-embedded glycoproteins E1 and E2. These glycoproteins are modified posttranslationally by the addition of palmitic acid, and inhibitors of acylation interfere with this budding process (M.J. Schlesinger and C. Malfer, J. Biol. Chem. 257:9887-9890, 1982). This report describes the use of site-directed mutagenesis to identify two of the acylation sites in the E2 glycoprotein as the cysteines near the carboxyl terminus of the protein which is oriented to the cytoplasmic domain of this type 1 transmembrane protein. Additional mutations were made at two prolines within a hydrophobic sequence of E2 that is highly conserved among several alphaviruses, and the mutant viruses were aberrant in assembly and particle formation. These data support earlier studies indicating that the native structure of the cytoplasmic domain of E2 is essential for proper assembly of this enveloped virus. PMID- 8474161 TI - A transcription initiation site for the hepatitis B virus X gene is directed by the promoter-binding protein. AB - Recent studies have demonstrated the transacting function of the X gene product of hepatitis B virus. However, little information is available on the regulation of X gene expression. In this report, we first investigate a cellular factor regulating X gene transcription by DNA transfection, using the human hepatoma cell line HuH-7, which is permissive for HBV replication as well as X mRNA transcription. A sequence-specific cellular factor was found to bind to the promoter region upstream of the first ATG (nucleotide [nt] 1248) of the X open reading frame. DNase I footprinting analysis showed the binding sequence of this factor to be situated between nt 1097 and 1119, where an 8-bp palindrome structure resides. S1 nuclease analysis of X gene transcripts demonstrated the binding site to be adjacent to two major start sites (nt 1117 and 1125) of X mRNA. Second, we demonstrate that introduction of a mutation into the binding site gives rise to a loss of the binding with a concomitant shift of the transcription start site of X mRNA beyond the 8-bp palindrome structure, causing it to become more heterogeneous. Thus, the promoter-binding protein appears to be involved in directing the transcription initiation site of the X gene toward the downstream region of the X promoter when X protein is produced from X mRNA. PMID- 8474162 TI - Human immunodeficiency virus type 1 envelope gp120 is cleaved after incubation with recombinant soluble CD4. AB - Human immunodeficiency virus type 1 (HIV-1) infects human CD4+ cells by a high affinity interaction between its envelope glycoprotein gp120 and the CD4 molecule on the cell surface. Subsequent virus entry into the cells involves other steps, one of which could be cleavage of the gp120 followed by virus-cell fusion. The envelope gp120 is highly variable among different HIV-1 isolates, but conserved amino acid sequence motifs that contain potential proteolytic cleavage sites can be found. Following incubation with a soluble form of CD4, we demonstrate that gp120 of highly purified HIV-1 preparations is, without addition of exogenous proteinase, cleaved most likely in the V3 loop, yielding two proteins of 50 and 70 kDa. The extent of gp120 proteolysis is HIV-1 strain dependent and correlates with the recombinant soluble CD4 sensitivity to neutralization of the particular strain. The origin of the proteolytic activity in the virus preparations remains unclear. The results support the hypothesis that cleavage of gp120 is required for HIV infection of cells. PMID- 8474163 TI - Effects of baculovirus infection on IE1-mediated foreign gene expression in stably transformed insect cells. AB - Previously, we produced transformed insect cell lines that can express a selected foreign protein constitutively, in the absence of baculovirus infection (D. L. Jarvis, J. G. W. Fleming, G. R. Kovacs, M. D. Summers, and L. A. Guarino, Bio/Technology 8:950-955, 1990). These cells contain stably integrated copies of chimeric genes consisting of the promoter from an immediate-early baculovirus gene, IE1, and the sequences encoding either human tissue plasminogen activator or Escherichia coli beta-galactosidase. Transcription of the integrated genes in these cells is specifically controlled by the IE1 promoter. The purpose of this study was to determine how baculovirus infection influences IE1-mediated foreign protein production by these stably transformed insect cell lines. The results showed that viral infection transiently stimulated and then strongly inhibited the production of both tissue plasminogen activator, a secreted protein, and beta galactosidase, an intracellular protein. These effects reflected virus-induced changes in the steady-state levels of RNA produced by the integrated genes. Transient assays showed that expression of the viral IEN gene alone could account for the increased levels of RNA observed early in infection. The precise mechanism accounting for the decreased levels of RNA observed later in infection was not determined. However, we obtained evidence that the native IE1 promoter remains active throughout infection, which suggested indirectly that the integrated IE1 promoter is transcriptionally inactivated at late times of baculovirus infection. Thus, the same promoter behaved quite differently late in infection, depending on its local environment. Neither methylation nor degradation appeared to be responsible for inactivating IE1-mediated expression of the integrated genes. The significance of these results with respect to the baculovirus-host interaction and the practical applications of stably transformed insect cell lines are discussed. PMID- 8474164 TI - A Friend virus mutant that overcomes Fv-2rr host resistance encodes a small glycoprotein that dimerizes, is processed to cell surfaces, and specifically activates erythropoietin receptors. AB - The env gene of Friend spleen focus-forming virus (SFFV) encodes a membrane glycoprotein (gp55) that is inefficiently (3 to 5%) processed from the rough endoplasmic reticulum to form a larger dimeric plasma membrane derivative (gp55p). Moreover, the SFFV env glycoprotein associates with erythropoietin receptors (EpoR) to cause proliferation of infected erythroblasts [J.-P. Li, A. D. D'Andrea, H. F. Lodish, and D. Baltimore, Nature (London) 343:762-764, 1990]. Interestingly, the mitogenic effect of SFFV is blocked in mice homozygous for the Fv-2r resistance gene, but mutant SFFVs can overcome this resistance. Recent evidence suggested that these mutants contain partial env deletions that truncate the membrane-proximal extracellular domain of the encoded glycoproteins (M. H. Majumdar, C.-L. Cho, M. T. Fox, K. L. Eckner, S. Kozak, D. Kabat, and R. W. Geib, J. Virol. 66:3652-3660, 1992). Mutant BB6, which encodes a gp42 glycoprotein that has a large deletion in this domain, causes erythroblastosis in DBA/2 (Fv-2s) as well as in congenic D2.R (Fv-2r) mice. Analogous to gp55, gp42 is processed inefficiently as a disulfide-bonded dimer to form cell surface gp42p. Retroviral vectors with SFFV and BB6 env genes have no effect on interleukin 3-dependent BaF3 hematopoietic cells, but they cause growth factor independency of BaF3/EpoR cells, a derivative that contains recombinant EpoR. After binding 125I-Epo to surface EpoR on these factor-independent cells and adding the covalent cross linking reagent disuccinimidyl suberate, complexes that had immunological properties and sizes demonstrating that they consisted of 125I-Epo-gp55p and 125I Epo-gp42p were isolated from cell lysates. Contrary to a previous report, SFFV or BB6 env glycoproteins did not promiscuously activate other members of the EpoR superfamily. Although the related env glycoproteins encoded by dualtropic murine leukemia viruses formed detectable complexes with EpoR, strong mitogenic signalling did not ensue. Our results indicate that the SFFV and BB6 env glycoproteins specifically activate EpoR; they help to define the glycoprotein properties important for its functions; and they strongly suggest that the Fv-2 leukemia control gene encodes an EpoR-associated regulatory factor. PMID- 8474165 TI - Comparison of DNA binding and integration half-site selection by avian myeloblastosis virus integrase. AB - Insertion of the linear retrovirus DNA genome into the host DNA by the virus encoded integrase (IN) is essential for efficient replication. We devised an efficient virus-like DNA plasmid integration assay which mimics the standard oligonucleotide assay for integration. It permitted us to study, by electron microscopy and sequence analysis, insertion of a single long terminal repeat terminus (LTR half-site) of one plasmid into another linearized plasmid. The reaction was catalyzed by purified avian myeloblastosis virus IN in the presence of Mg2+. The recombinant molecules were easily visualized and quantitated by agarose gel electrophoresis. Agarose gel-purified recombinants could be genetically selected by transformation of ligated recombinants into Escherichia coli HB101 cells. Electron microscopy also permitted the identification and localization of IN-DNA complexes on the virus-like substrate in the absence of the joining reaction. Intramolecular and intermolecular DNA looping by IN was visualized. Although IN preferentially bound to AT-rich regions in the absence of the joining reaction, there was a bias towards GC-rich regions for the joining reaction. Alignment of 70 target site sequences 5' of the LTR half-site insertions with 68 target sites previously identified for the concerted insertion of both LTR termini (LTR full-site reaction) indicated similar GC inflection patterns with both insertional events. Comparison of the data suggested that IN recognized only half of the target sequences necessary for integration with the LTR half-site reaction. PMID- 8474166 TI - Competition between baculovirus polyhedrin and p10 gene expression during infection of insect cells. AB - Polyhedrin and p10 genes are expressed concurrently during the late stage of infection. To determine whether any competition occurs between these two genes at a transcriptional and/or translational level, a series of Autographa californica nuclear polyhedrosis recombinant viruses with deletions of promoter and coding sequences of the p10 or polyhedrin gene was constructed. Two modified baculoviruses with only one of the very late promoters, single late-promoter viruses AcSLP10 and AcSLP33, were made. The polyhedrin gene was used as a reporter gene to allow direct comparison between p10 and polyhedrin-driven expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and [35S]methionine labeling experiments showed that polyhedrin synthesis is enhanced in cells infected with baculoviruses carrying only one very late promoter. However, this enhancement is more significant when the polyhedrin gene is located in its natural site. Dot blot hybridization experiments carried out with total cytoplasmic RNA showed that deletion of the p10 promoter resulted in an increase of mRNAs derived from the polyhedrin promoter. In contrast, no increase of p10-promoted mRNA was detected when the polyhedrin gene promoter was deleted. PMID- 8474167 TI - Relating structure to function in the hepatitis delta virus antigen. AB - Hepatitis delta virus expresses two forms of a single protein, the small (delta Ag-S) and large (delta Ag-L) antigens, which are identical except for an additional 19 residues present at the C terminus of delta Ag-L. While delta Ag-S is required to promote genome replication, delta Ag-L potently inhibits this process and also facilitates packaging of the viral genome by envelope proteins of the helper virus (hepatitis B virus). Regions within the antigens responsible for nuclear localization, RNA binding, and dimerization have been identified, yet it is not clear how these particular activities contribute to the ultimate replication and packaging phenotypes. Here we report the following findings. (i) Although the removal of the nuclear localization signal from either antigen resulted in significant cytoplasmic accumulation, both proteins still had access to the nucleus. As a consequence, no functional defect was observed with either mutant. (ii) The RNA-binding domain, although necessary for delta Ag-S function, could be deleted from delta Ag-L without compromising its ability to either inhibit replication or promote packaging. (iii) In contrast, the coiled-coil dimerization domain was required for both the activation of replication by delta Ag-S and the inhibition of replication by delta Ag-L. This region, with an additional 20 amino acids C-terminal to it, was necessary and sufficient to potently inhibit replication by interacting with the small antigen. (iv) The packaging property of delta Ag-L required a C-terminal Pro/Gly-rich region which is hypothesized to interact with the hepatitis B virus envelope proteins during the assembly process. PMID- 8474168 TI - Simian immunodeficiency virus RNA is efficiently encapsidated by human immunodeficiency virus type 1 particles. AB - Packaging of retroviral RNA is attained through the specific recognition of a cis acting encapsidation site (located near the 5' end of the viral RNA) by components of the Gag precursor protein. Human immunodeficiency virus type 1 (HIV 1) and simian immunodeficiency virus (SIV) are two lentiviruses that lack apparent sequence similarity in their putative encapsidation regions. We used SIV vectors to determine whether HIV-1 particles can recognize the SIV encapsidation site and functionally propagate SIV nucleic acid. SIV nucleic acid was replicated by HIV-1 proteins. Thus, efficient lentivirus pseudotyping can take place at the RNA level. Direct examination of the RNA contents of virus particles indicated that encapsidation of this heterologous RNA is efficient. Characterization of deletion mutants in the untranslated leader region of SIV RNA indicates that only a very short region at the 5' end of the SIV RNA is needed for packaging. Comparison of this region with the corresponding region of HIV-1 reveals that both are marked by secondary structures that are likely to be similar. Thus, it is likely that a similar higher-order RNA structure is required for encapsidation. PMID- 8474169 TI - Complement-mediated binding of naturally glycosylated and glycosylation-modified human immunodeficiency virus type 1 to human CR2 (CD21). AB - Particulate glycoproteins lacking sialic acid, such as desialylated enveloped viruses, readily activate complement through the alternative pathway. Human immunodeficiency virus type 1 (HIV-1) contains two heavily glycosylated and partially sialylated envelope glycoproteins: a surface gp120 and a transmembrane gp41. The abilities of naturally glycosylated HIV-1 and glycosylation-modified HIV-1 to interact with the complement system were examined with a biological assay which measured the binding of whole virus particles to cells expressing CR2 (CD21), the complement receptor found naturally in abundance on follicular dendritic cells and immature B cells. HIV-1 IIIB was synthesized in the presence or absence of the mannosidase II inhibitor, swainsonine, to give rise to high mannose-type, nonsialylated, nonfucosylated carbohydrate moieties. The virus also was treated with neuraminidase or endo-beta-galactosidase to remove terminal sialic acids. An enzyme immunoassay specific for HIV-1 p24 core protein was used to quantitate the amount of virus bound to cell surfaces. Virus particles incubated with 1:3-diluted, fresh HIV-1-negative human serum as a source of complement readily bound to MT-2 (CD4+ CR2+) and Raji-3 (CD4- CR2+) cells but not to CEM (CD4+ CR2-) cells, suggesting that the virus bound to CR2 independently of CD4. Compared with heat-inactivated or C3-deficient sera, fresh complement increased binding by as much as 62 times for naturally glycosylated virus, and 5 times more than this for glycosylation-modified virus. Similar observations were made with freshly isolated, non-mitogen-stimulated peripheral blood mononuclear cells. Additional evidence that HIV-1 bound to CR2 independently of CD4 was provided by the fact that binding was blocked by monoclonal antibody OKB7 (anti CR2) but not by OKT4a (anti-CD4). Also, the virus bound to transfected K562 cells (CD4-) which expressed recombinant human CR2 but did not bind to untransfected K562 cells. Results obtained with complement component-deficient sera indicated that binding required the alternative complement pathway. Raji-3 and transfected K562 cells could not be infected with HIV-1 in the presence of complement, suggesting that utilization of CR2 as a receptor in the absence of CD4 does not allow virus entry. The demonstration of CR2 as a receptor for HIV-1 in the presence of complement, together with the ability to enhance binding by desialylation, provides new insights into mechanisms of HIV-1-induced immunity and immunopathogenesis. PMID- 8474170 TI - Flock house virus: down-regulation of subgenomic RNA3 synthesis does not involve coat protein and is targeted to synthesis of its positive strand. AB - Flock house virus is a small insect virus with a bipartite RNA genome consisting of RNA1 and RNA2. RNA3 is a subgenomic element encoded by RNA1, the genomic segment required for viral RNA synthesis (T. M. Gallagher, P. D. Friesen, and R. R. Rueckert, J. Virol. 46:481-489, 1983). Synthesis of RNA3 is strongly inhibited by RNA2, the gene for viral coat protein. Evidence that coat protein is not the regulatory element was obtained by using a defective interfering RNA2 which was messenger inactive. It was also found that RNA2 selectively down-regulated synthesis of positive-strand RNA3 but not of its complementary negative strand. cDNA-generated RNA2 transcripts, carrying four extra nonviral bases at the 3' end, failed to repress synthesis of RNA3 but recovered this activity after a single passage in Drosophila cells in the presence of RNA1, suggesting that down regulation of RNA3 synthesis is controlled by competition with RNA2 for viral replicase. PMID- 8474171 TI - Analysis of the evolution and variation of the human influenza A virus nucleoprotein gene from 1933 to 1990. AB - This study examined the evolution and variation of the human influenza virus nucleoprotein gene from the earliest isolates to the present. Phylogenetic reconstruction of the most parsimonious evolutionary path connecting 49 nucleoprotein sequences yielded a single lineage. The average calculated rate of mutation was 3.6 nucleotide substitutions per year (2.3 x 10(-3) substitutions per site per year). Thirty-two percent of these mutations resulted in amino acid substitutions, and the remainder were silent mutations. Analysis of virus isolates from China and elsewhere showed no significant differences in their rate of evolution, genetic diversity, or mean survival time. The nearly constant rate of change was maintained through the two antigenic shifts, and there were no obvious changes in the number or types of mutations associated with the changes in the surface proteins. A detailed comparison of the changes that have occurred on the main evolutionary path with those that have occurred on the side branches of the phylogenetic tree was made. This showed that while 35% of the mutations on the side branches resulted in amino acid changes, only 21% of those on the main path affected the protein sequence. These results suggest that although the rate of change of the human influenza virus nucleoprotein is much higher than that previously described for avian influenza viruses, there are measurable constraints on the evolution of the surviving virus lineage. Comparison of the nucleoproteins of virus isolates adapted to chicken embryos with the nucleoproteins of those grown only in MDCK cells revealed no consistent differences between the virus pairs. Thus, although the nucleoprotein is known to be critical for host specificity, its adaptation to growth in eggs apparently involves no immediate selective pressures, such as are found with hemagglutinin. PMID- 8474172 TI - Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. AB - Changes were introduced into conserved amino acids within the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein. The effect of these changes on the structure and function of the HIV-1 envelope glycoproteins was examined. The gp41 glycoprotein contains an amino-terminal fusion peptide (residues 512 to 527) and a disulfide loop near the middle of the extracellular domain (residues 598 to 604). Mutations affecting the hydrophobic sequences between these two regions resulted in two phenotypes. Some changes in amino acids 528 to 562 resulted in a loss of the noncovalent association between gp41 and the gp120 exterior glycoprotein. Amino acid changes in other parts of the gp41 glycoprotein (residues 608 and 628) also resulted in subunit dissociation. Some changes affecting amino acids 568 to 596 resulted in envelope glycoproteins partially or completely defective in mediating membrane fusion. Syncytium formation was more sensitive than virus entry to these changes. Changes in several amino acids from 647 to 675 resulted in higher-than-wild-type syncytium-forming ability. One of these amino acid changes affecting tryptophan 666 resulted in escape from neutralization by an anti-gp41 human monoclonal antibody, 2F5. These results contribute to an understanding of the functional regions of the HIV-1 gp41 ectodomain. PMID- 8474173 TI - Use of recombinant baculoviruses in synthesis of morphologically distinct viruslike particles of flock house virus, a nodavirus. AB - Flock house virus (FHV) is a small icosahedral insect virus of the family Nodaviridae. Its genome consists of two messenger-sense RNA molecules, both of which are encapsidated in the same particle. RNA1 (3.1 kb) encodes proteins required for viral RNA replication; RNA2 (1.4 kb) encodes protein alpha (43 kDa), the precursor of the coat protein. When Spodoptera frugiperda cells were infected with a recombinant baculovirus containing a cDNA copy of RNA2, coat protein alpha assembled into viruslike precursor particles (provirions) that matured normally by autocatalytic cleavage of protein alpha into polypeptide chains beta (38 kDa) and gamma (5 kDa). The particles were morphologically indistinguishable from authentic FHV and contained RNA derived from the coat protein message. These results showed that RNA1 was required neither for virion assembly nor for maturation of provirions. Expression of mutants in which Asn-363 at the beta gamma cleavage site of protein alpha was replaced by either aspartate, threonine, or alanine resulted in assembly of particles that were cleavage defective. For two of the mutants, unusual structural features were observed after preparation for electron microscopy. Particles containing Asp at position 363 were labile and showed a strong tendency to break into half-shells. Particles in which Asn-363 was replaced by Ala displayed a distinct hole in an otherwise complete shell. The third mutant, containing Thr at position 363, was indistinguishable in morphology from authentic FHV. PMID- 8474174 TI - Elimination of L-A double-stranded RNA virus of Saccharomyces cerevisiae by expression of gag and gag-pol from an L-A cDNA clone. AB - We report that expression of a nearly full-length cDNA clone of the L-A double stranded RNA virus causes virus loss in a wild-type strain of Saccharomyces cerevisiae. We show that in this system exclusion of the L-A virus is independent of the presence of the packaging site or of cis sites for replication and transcription and completely dependent on expression of functional recombinant gag and gag-pol fusion protein. Thus, this exclusion is not explained in terms of overexpression of packaging signals. Mutation of the chromosomal SKI2 gene, known to repress the copy number of double-stranded RNA cytoplasmic replicons of S. cerevisiae, nearly eliminates the exclusion. We suggest that exclusion is due to competition by proteins expressed from the plasmid for a possibly limiting cellular factor. Our hypotheses on exclusion of L-A proteins may also apply to resistance to plant viruses produced by expression of viral replicases in transgenic plants. PMID- 8474175 TI - Assembly-defective point mutants of the human immunodeficiency virus type 1 Gag precursor phenotypically expressed in recombinant baculovirus-infected cells. AB - Two substitution mutants of the human immunodeficiency virus type 1 gag gene product were isolated after nitrous acid mutagenesis of a recombinant baculovirus expressing a non-N-myristylated, p6-deleted Gag precursor (Pr49). Both mutants failed to assemble intracellular Gag virus-like particles, as does the parental recombinant, and therefore expressed a self-assembly defective (Sad) phenotype in insect cells. The mutations consisted of nonconservative changes involving highly conserved hydrophobic residues in the p24 domain, Leu to Pro at position 268 (L268P) and Leu to Ser at amino acid 322 (L322S). Experimental data suggested that the two mutated residues belonged to functionally different regions of the Gag precursor. (i) A partial complementation effect between the two mutants for Gag precursor assembly was observed in coinfection experiments. (ii) The two mutations showed different phenotypes when placed in the N-myristylated context, of which only the L268P mutation abolished extracellular budding and release of Gag particles at the plasma membrane. Both L268P and L322S mutants had a trans dominant negative effect on the intracellular assembly of a non-N-myristylated, full-length (Pr55) Gag precursor expressed by a coinfecting recombinant. None of the mutants, however, showed any detectable effect in trans on membrane targeting and budding of the coexpressed N-myristylated wild-type Gag precursor. PMID- 8474176 TI - Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein increases env incorporation into particles and fusogenicity and infectivity. AB - Growth of macaque simian immunodeficiency virus (SIVmac) in certain cloned human T-cell lines, such as HUT.78, selects for isolates containing a premature stop codon within the cytoplasmic domain of the transmembrane envelope glycoprotein. In contrast, propagation of virus in macaques or in their cultured T cells favors replication of virus containing the full-length envelope glycoprotein. To elucidate the causes of this phenomenon, we used a human immunodeficiency virus pseudotyping system to assess the effects on infectivity of the cytoplasmic domains of envelope glycoproteins obtained from SIVmac1A11 and SIVmac239. These envelopes contain truncated and full-length cytoplasmic domains, respectively. By analyzing human immunodeficiency virus particles containing selectable genes pseudotyped with each glycoprotein or with chimeric derivatives, we found that truncation of the cytoplasmic domain resulted in a significant advantage in viral entry into HUT.78 T cells and CD4+ U87.MG glial cells. Truncation of the cytoplasmic domain significantly enhanced both envelope density on particles and envelope-mediated cell-to-cell fusion. It is likely that one or both of these effects contribute to the observed differences in infectivity and to the selection of virions with short cytoplasmic tails in human T cells. PMID- 8474177 TI - The RRE of human immunodeficiency virus type 1 contributes to cell-type-specific viral tropism. AB - As part of a general program investigating the mechanism of the Rev axis of human immunodeficiency virus type 1 (HIV-1) autoregulation, a series of proviral HIV-1 mutants which differ from the parental HXB2 strain at selected positions within the RRE were constructed. All of the mutations were designed to perturb the RRE by introducing local helix disruptions without altering the coding potential of the overlapping envelope open reading frame. Viral replication in various cell types was monitored by a cell supernatant reverse transcriptase assay and Northern (RNA blot) analysis. All proviral RRE mutants displayed at least some impairment in replication. However, the relative impairment varied drastically among the various cell types tested. This suggests that the RRE may contribute to cell-type-specific viral tropism. PMID- 8474178 TI - Sequences downstream of the RNA initiation site regulate human T-cell lymphotropic virus type I basal gene expression. AB - Sequences which control basal human T-cell lymphotropic virus type I (HTLV-I) transcription probably play an important role in initiation and maintenance of virus replication. We have identified and analyzed a 45-nucleotide sequence (downstream regulatory element 1 [DRE 1]) at the boundary of the R/U5 region of the long terminal repeat which is required for HTLV-I basal transcription. The basal promoter strength of constructs that contained deletions in the R/U5 region of the HTLV-I long terminal repeat were analyzed by chloramphenicol acetyltransferase assays following transfection of Jurkat T cells. We consistently observed a 10-fold decrease in basal promoter activity when sequences between +202 to +246 were deleted. By reverse transcriptase polymerase chain reaction RNA analysis, we confirmed that the drop in chloramphenicol acetyltransferase activity was paralleled by a decrease in the level of steady state RNA. DRE 1 did not affect the level of Tax1 transactivation. Using a gel shift assay, we have purified a highly enriched fraction that could specifically bind DRE 1. This DNA affinity column fraction contained four detectable proteins on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis: p37, p50, p60, and p100. The affinity column fraction stimulated HTLV-I transcription approximately 12-fold in vitro. No effect was observed with the human immunodeficiency virus or adenovirus major late promoters. Following renaturation of the proteins isolated from an SDS-containing gel, p37, but not the other protein fractions, was able to specifically bind to DRE 1. PMID- 8474179 TI - The NF-kappa B binding site is necessary for efficient replication of simian immunodeficiency virus of macaques in primary macrophages but not in T cells in vitro. AB - We demonstrate here that the nuclear factor-kappa B (NF-kappa B) binding site in the simian immunodeficiency virus (SIVmac) long terminal repeat is essential for efficient virus replication in primary alveolar macrophages but dispensable for efficient replication in primary T cells. Mutation of the NF-kappa B site does not seriously impair replication of a T-cell-tropic SIVmac239 or a macrophagetropic SIVmacEm* in peripheral blood lymphocytes or established CD4+ cell lines; however, mutation of the NF-kappa B site prevents efficient SIVmacEm* replication in primary alveolar macrophages. These data suggest that efficient replication in primary macrophages requires both envelope and long terminal repeat determinants. PMID- 8474180 TI - Cellular immune response to hog cholera virus (HCV): T cells of immune pigs proliferate in vitro upon stimulation with live HCV, but the E1 envelope glycoprotein is not a major T-cell antigen. AB - T-cell responses of pigs to hog cholera virus (HCV) have reportedly been absent or difficult to detect. Therefore, little is known about cellular immunity to HCV. In this study, we used an attenuated strain of pseudorabies virus expressing the envelope glycoprotein E1 of HCV and purified recombinant E1 to examine whether the E1 protein is a target antigen recognized by the T cells of HCV immune pigs. We were unable to identify the E1 protein as a major target antigen recognized by the T cells of HCV-immune animals. However, such cells proliferated in vitro upon stimulation with viable HCV antigen. The lymphoproliferative response to HCV was strictly time and dose dependent and could be induced upon stimulation by live but not by UV light-inactivated HCV. Depletion studies demonstrated that lymphoproliferation depended on the presence of CD2+CD8bright+ lymphocytes, but CD2+CD4+ cells also contributed to the lymphoproliferative response. The primary lymphoproliferative response in animals inoculated with 10(7) 50% tissue culture infective doses of strain Brescia 2.1.1 was stronger than that observed in animals inoculated with 10(3) 50% tissue culture infective doses of the Cedipest strain. A remarkable finding was the increase in non antigen-specific lymphoproliferation upon inoculation of the animals with HCV strains. This immunological phenomenon may mask a specific T-cell response to the virus. PMID- 8474181 TI - Identification of an amino acid that defines the fusogenicity of mumps virus. AB - Recombinant cDNA clones representing the fusion (F) and hemagglutinin neuraminidase (HN) proteins of two mumps virus strains different in fusogenicity were constructed. Upon transfection of COS7 cells, extensive cell fusion was observed only when cells expressed the F protein of the fusing strain together with the HN protein derived from either strain. Mutational analyses further showed that the amino acid at position 195 of the F protein plays a critical role in determining the extent of cell fusion induced by mumps virus, since replacement of Ser-195 by Tyr significantly reduced the fusion inducibility of otherwise fusion-competent F protein. PMID- 8474182 TI - Dilute passage promotes expression of genetic and phenotypic variants of human immunodeficiency virus type 1 in cell culture. AB - We have studied the extent of genetic and phenotypic diversification of human immunodeficiency virus type 1 (HIV-1) upon 15 serial passages of clonal viral populations in MT-4 cell cultures. Several genetic and phenotypic modifications previously noted during evolution of HIV-1 in infected humans were also observed upon passages of the virus in cell culture. Notably, the transition from non syncytium-inducing to syncytium-inducing phenotype (previously observed during disease progression) and fixation of amino acid substitutions at the main antigenic loop V3 of gp120 were observed in the course of replication of the virus in MT-4 cell cultures in the absence of immune selection. Interestingly, most genetic and phenotypic alterations occurred upon passage of the virus at a low multiplicity of infection (0.001 infectious particles per cell) rather than at a higher multiplicity of infection (0.1 infectious particles per cell). The degree of genetic diversification attained by HIV-1, estimated by the RNase A mismatch cleavage method and by nucleotide sequencing, is of about 0.03% of genomic sites mutated after 15 serial passages. This value is not significantly different from previous estimates for foot-and-mouth disease virus when subjected to a similar process and analysis. We conclude that several genetic and phenotypic modifications of HIV-1 previously observed in vivo occur also in the constant environment provided by a cell culture system. Dilute passage promotes in a highly significant way the expression of deviant HIV-1 genomes. PMID- 8474183 TI - Induction of the cell cycle in baby rat kidney cells by adenovirus type 5 E1A in the absence of E1B and a possible influence of p53. AB - From previous studies on the induction of DNA synthesis in quiescent primary baby rat kidney cells by adenovirus type 5 (Ad5) E1A deletion mutants, we concluded that induction is prevented only when cellular proteins p300 and pRb are both uncomplexed with E1A (J.A. Howe, J.S. Mymryk, C. Egan, P.E. Branton, and S.T. Bayley, Proc. Natl. Acad. Sci. USA 87:5883-5887, 1990). We have now examined induction by these same mutants in virus lacking the E1B region, so that cellular p53 was no longer complexed to the E1B 55-kDa protein. E1A mutants that fail to bind pRb induced DNA synthesis at a significantly lower level in Ad5 lacking E1B than in Ad5 containing E1B. Apparently, therefore, uncomplexed p53 can partially replace p300 in cooperating with pRb to suppress DNA synthesis in baby rat kidney cells. PMID- 8474184 TI - Crystallization of viruslike particles assembled from flock house virus coat protein expressed in a baculovirus system. AB - Flock house virus coat protein expressed in a baculovirus system spontaneously assembles into viruslike particles, which undergo an autocatalytic postassembly cleavage equivalent to that of the native virus. Mutations of the asparagine at the Asn/Ala cleavage site result in assembly of provirion-like particles that are cleavage defective. Crystals of the mutant provirions have been grown, and they diffract X rays beyond 3.3-A (0.33-nm) resolution. The crystals are monoclinic space group P2(1) (a = 464.8 A [46.48 nm]; b = 333.9 A [33.39 nm]; c = 325.2 A [32.52 nm]; beta = 91.9 degrees) with two provirion-like particles per unit cell. Thus, it should be possible to determine the high-resolution structure of the provirion, which will be compared with the crystal structure of the mature authentic virion. This collation should provide mechanistic detail for understanding the cleavage event. Moreover, this demonstrates that the baculovirus expression system displays sufficient fidelity to permit crystallographic analysis of the assembly process of biological macromolecules. PMID- 8474185 TI - Gene therapy for brain tumors in trials, correction of inherited disorders a hope. PMID- 8474186 TI - Novel therapies dominate American Cancer Society's 35th Annual Science Writers Seminar. PMID- 8474187 TI - For AIDS treatment, vaccines, now think genes. PMID- 8474188 TI - From the Centers for Disease Control and Prevention. Update: multistate outbreak of Escherichia coli O157:H7 infections from hamburgers--Western United States, 1992-1993. PMID- 8474189 TI - The myth of the abortion trauma syndrome revisited. PMID- 8474190 TI - The myth of the abortion trauma syndrome revisited. PMID- 8474191 TI - The myth of the abortion trauma syndrome revisited. PMID- 8474192 TI - Parental consent for abortion. PMID- 8474193 TI - Parental consent for abortion. PMID- 8474194 TI - Abortion mortality trends. PMID- 8474195 TI - Motor vehicles or firearms: which takes a heavier toll? PMID- 8474196 TI - Smoking cessation and risk of stroke in women. PMID- 8474197 TI - Smoking cessation and risk of stroke in women. PMID- 8474198 TI - Smoking cessation and risk of stroke in women. PMID- 8474199 TI - Smoking cessation and risk of stroke in women. PMID- 8474200 TI - An outbreak of diarrhea and hemolytic uremic syndrome from Escherichia coli O157:H7 in fresh-pressed apple cider. AB - OBJECTIVE: Escherichia coli O157:H7 causes hemorrhagic colitis and the hemolytic uremic syndrome. In the fall of 1991, an outbreak of E coli O157:H7 infections in southeastern Massachusetts provided an opportunity to identify transmission by a seemingly unlikely vehicle. DESIGN: Case-control study to determine the vehicle of infection. New England cider producers were surveyed to assess production practices and determined the survival time of E coli O157:H7 organisms in apple cider. RESULTS: Illness was significantly associated with drinking one brand of apple cider. Thirteen (72%) of 18 patients but only 16 (33%) of 49 controls reported drinking apple cider in the week before illness began (odds ratio [OR], 8.3; 95% confidence interval [CI], 1.8 to 39.7). Among those who drank cider, 12 (92%) of 13 patients compared with two (13%) of 16 controls drank cider from cider mill A (lower 95% CI, 2.9; P < .01). This mill pressed cider in a manner similar to that used by other small cider producers: apples were not washed, cider was not pasteurized, and no preservatives were added. In the laboratory, E coli O157:H7 organisms survived for 20 days in unpreserved refrigerated apple cider. Addition of sodium benzoate 0.1% reduced survival to less than 7 days. CONCLUSIONS: Fresh-pressed, unpreserved apple cider can transmit E coli O157:H7 organisms, which cause severe infections. Risk of transmission can be reduced by washing and brushing apples before pressing, and preserving cider with sodium benzoate. Consumers can reduce their risk by only drinking cider made from apples that have been washed and brushed. PMID- 8474202 TI - Association of tuberculosis infection with increased time in or admission to the New York City jail system. AB - OBJECTIVE: To establish the association between time spent in jail or number of jail admissions and development of tuberculosis in a cohort of inmates incarcerated without evidence of tuberculosis infection on entry. DESIGN: Nested case-control design within a prospective cohort. A cohort of 2636 tuberculin skin test-negative inmates incarcerated in 1985 was matched against the Tuberculosis Registry of New York City. Each case of tuberculosis reported prior to May 15, 1992, was assigned to three randomly selected controls from the cohort. We determined time spent in jail by reviewing the computer records of the New York City Inmate Information System. Conditional logistic regression modeling was performed to establish the association of jail time with the development of tuberculosis. SETTING: New York City Jail. RESULTS: Sixty inmates developed tuberculosis by May 15, 1992. Eighty-five percent of these had pulmonary tuberculosis. Univariate analysis identified the number of jail admissions (P = .02), age greater than or equal to 30 years (P = .001), and assignment to a methadone detoxification unit (P = .001) as significant in predicting tuberculosis. Multivariate modeling identified these same variables and jail time as significant. One year of jail time increased the odds of tuberculosis to 2.2 (95% confidence interval, 1.1 to 4.4). CONCLUSION: The demonstrated association between jail time or jail admissions and development of tuberculosis suggests that the New York City jail system may be an important amplification point in the ongoing tuberculosis epidemic, deserving significant public health attention. PMID- 8474201 TI - A controlled trial of HA-1A in a canine model of gram-negative septic shock. AB - OBJECTIVE: To investigate the therapeutic efficacy and microbiological and physiological effects of a human IgM monoclonal antibody (HA-1A) directed against the lipid A component of endotoxin in a canine model of sepsis that simulates the cardiovascular abnormalities of human septic shock. DESIGN: Blinded, placebo controlled 28-day trial. INTERVENTIONS: Purpose-bred beagles were implanted with an intraperitoneal clot infected with Escherichia coli O111:B4. At clot placement, animals received HA-1A (10 mg.kg-1), control human IgM antibody (10 mg.kg-1), or control human serum albumin intravenously. All animals were given antibiotic and fluid therapy. MEASURES: Survival and microbiological and physiological events. RESULTS: Only two (15%) of 13 animals in the HA-1A group, compared with eight (57%) of 14 control animals (combined control human IgM antibody and control human serum albumin groups) (P = .05), survived 28 days. At 24 hours, the HA-1A group had lower mean arterial pressure (P = .04) and cardiac index (P = .004) and higher lactate levels (P = .05) compared with the combined controls group. In addition, these parameters in the HA-1A group were significantly more predictive of death. The HA-1A and combined-controls groups had similar significant increases in the level of endotoxemia and bacteremia. Studies of toxic effects showed no harmful effects of control human IgM antibody in infected animals or HA-1A in non-infected animals. CONCLUSION: In a canine model of E coli sepsis, HA-1A did not alter levels of bacteremia or endotoxemia and actually decreased survival. If these data are relevant to human septic shock, HA-1A therapy should be limited until the conditions under which this monoclonal antibody has beneficial or deleterious effects are more completely defined. PMID- 8474203 TI - The nation's changing blood supply system. PMID- 8474204 TI - Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac) AB - OBJECTIVE: To compare pregnancy outcome following first-trimester fluoxetine (Prozac) exposure with pregnancy outcome in two matched control groups. Fluoxetine is a new antidepressant used by many young women. Currently, no published data exist on its safety in pregnancy. DESIGN: We prospectively collected and followed up 128 pregnant women exposed to a mean daily dose of 25.8 mg (+/- 13 mg) of fluoxetine during the first trimester and compared pregnancy outcome with two matched groups of women exposed during the first trimester of pregnancy to either nonteratogens or tricyclic antidepressants. RESULTS: Rates of major malformations were comparable within the three groups and did not exceed those expected in the general population. Women treated with fluoxetine had a tendency for increased risk for miscarriage when compared with women exposed to nonteratogens (relative risk, 1.9; 95% confidence interval, 0.92 to 3.92). The rate of miscarriages in the fluoxetine group was comparable with the tricyclic group (13.5% and 12.2% vs 6.8% in the nonteratogens). CONCLUSIONS: Our study suggests that the use of fluoxetine during embryogenesis is not associated with an increased risk of major malformations. Women exposed to both fluoxetine and tricyclic antidepressants tended to report higher rates of miscarriage; further studies will be needed to confirm this observation and to separate the effects of the psychiatric condition from the associated drugs. Long-term studies will be warranted to rule out potential developmental teratology of fluoxetine, which affects a central nervous system neurotransmitter. PMID- 8474205 TI - Planned Parenthood v Casey. The impact of the new undue burden standard on reproductive health care. AB - The recent US Supreme Court decision in Planned Parenthood v Casey, by changing the legal standard by which restrictions on abortion are evaluated, will have a profound effect on access to reproductive health care in the United States. This article reviews the Pennsylvania antiabortion restrictions at issue in Casey and discusses the ways in which the new constitutional standard fundamentally weakens the legal protections previously afforded women and physicians in the 1973 case, Roe v Wade. While the majority opinion reaffirmed a woman's right to choose an abortion, the opinion opens the door to a multitude of new restrictive abortion laws, which diminish, and in some cases completely block, a woman's ability to exercise that right. The effect of weakened legal protection will fall most heavily on young, poor, minority, and rural women, who will be unable to overcome obstacles imposed by mandatory waiting periods, biased counseling, and parental notification requirements. The restrictions are also likely to exacerbate the shortage of physicians providing abortion services by making the procedure more costly and the providers' jobs more dangerous. Finally, the medical community can help to ensure women access to comprehensive and competent reproductive health care. PMID- 8474206 TI - The emergence of Escherichia coli O157:H7 infection in the United States. The changing epidemiology of foodborne disease. PMID- 8474207 TI - The search for a magic bullet to fight sepsis. PMID- 8474208 TI - The future of medicine. PMID- 8474209 TI - The future of world health. PMID- 8474210 TI - The future of US public health. PMID- 8474211 TI - Blood transfusion--a potential source of HIV/AIDS spread. PMID- 8474212 TI - Significance of thyroid microsomal antibody in Graves' disease. AB - Thyroid microsomal antibody (MsAb) was estimated in 48 patients with Graves' disease (15 newly diagnosed, 15 on drugs for about 4 weeks and 18 euthyroid with drug treatment) and twenty age and sex matched controls. The diagnosis of Graves' disease (GD) was based on clinical history, physical examination and thyroid function tests, viz. 131I uptake, thyroid scintigram and serum T3, T4 and TSH levels. MSAb was positive in 93.3% of newly diagnosed as well as hyperthyroid GD patients on drugs. Eighty-three percent euthyroid GD patients and 20% normal controls also showed MSAb positivity. The titres of newly diagnosed patients were significantly raised (P < 0.05) than those of euthyroid patients and controls indicating the diagnostic as well as prognostic significance of MSAb in Graves' disease. PMID- 8474213 TI - Acupuncture vs carbamazepine in trigeminal neuralgia. PMID- 8474214 TI - Childhood acute respiratory infection in Pakistan. PMID- 8474215 TI - Prevalence and pattern of HIV infection in Karachi. AB - Two thousand seven hundred and seventy six subjects comprising 844 high risk and 1932 low risk group were screened for HIV antibodies by ELISA and western blot. Eight subjects from high risk group were HIV positive. They included three prisoners, two sexually promiscuous, two seafarers and one recipient of blood. The highest prevalence of the infection was found in sexually promiscuous group (5.40% +/- 7.40) followed by prisoners (1.64% +/- 1.87), multitransfused patients (1.0% +/- 1.96) and seafarers (0.66% +/- 0.93). No case of HIV infection was found in low risk population group, however, one pregnant women had p24 and p55 antibodies on western blot. PMID- 8474216 TI - The blue rubber bleb syndrome. PMID- 8474217 TI - Intussusception in an infant caused by aberrant pancreas. PMID- 8474218 TI - Cysticercosis in a Muslim woman. PMID- 8474219 TI - Clinical and endocrine features of ultrasound diagnosed polycystic ovary patients: the correlation between ovarian volume and androgen activity. AB - One hundred and twenty five patients with polycystic ovaries on ultrasonography and 17 controls with normal ovaries on ultrasound and regular ovulary cycles underwent clinical and endocrine evaluation. Of 125 ultrasound-diagnosed polycystic ovary patients (PCO) 49.6% complained about hirsutism, 55.2% had menstrual disturbances (46.4% oligomenorrhea, 8.8% amenorrhea), 23.2% had normal but irregular cycles and 50.4% had infertility. PCO patients had significantly higher mean serum LH, testosterone, androstenedione and DHEAS levels and higher mean ovarian volume compared with the control group. Sixty seven percent of PCO patients had enlarged ovaries and significantly higher mean serum LH, testosterone, androstenedione and DHEAS levels, compared with the PCO patients who had ovarian volume within normal range. There was a significant positive correlation between ovarian volume and serum LH, testosterone, androstenedione, DHEAS levels. Hirsutism, oligomenorrhea, irregular cycles were equally present in patients with normal ovarian volume and enlarged ovaries. These results illustrate the importance of ovarian volume measurement as an indicator of androgen production in PCO patients. PMID- 8474220 TI - Merits of posterior lumbotomy approach to the upper urinary tract. AB - Posterior lumbotomy incision is anatomically the most straightforward approach to the kidney and the upper ureter. A brief description of the operative technique is followed by a report of the author's experience with this approach in 38 operations on the upper urinary tract. The access provided was judged to be adequate in 35 (92%) patients although twelve patients (31.5%) required upward extension of the incision for the access to become adequate. Thirty-three patients (87%) were mobile and did not require analgesia by third postoperative day. Average hospital stay was 6 days. Complications occurred in seven patients (21%). There was no hospital mortality. This incision is recommended for relatively simple operations of upper urinary tract like pyelolithotomy and ureterolithotomy. PMID- 8474221 TI - Bioburden and theoretical sterility dose calculation for radiation sterilization of surgical cotton and bandages. AB - The initial bioburden, count of colony forming unit (CFU) was determined on the locally manufactured non-sterilized surgical cotton and bandages. In all 489 tests were conducted on 163 cotton samples and 246 tests on 82 bandage samples. The surgical cotton showed an average of 198 microbes with a maxima of 287 and minima 94 whereas bandages showed an average of 179 microbes with a maxima of 268 and minima of 89. In the 20% samples subjected to identification no anaerobic microorganism was isolated while the aerobic microorganisms isolated were all bacilli. The sterilization dose (SD) for sterility assurance level (SAL) of 10( 6) was 2.23 Mrads and 2.21 Mrads, whereas the device verification dose (DVD) was 0.6 and 0.59 Mrads for cotton and bandages respectively as calculated by the method proposed by the Sterilization Standard Committee, Association of Advancement of Medical Instrumentation (AAMI). PMID- 8474222 TI - [Aging and intestinal flora]. PMID- 8474223 TI - [Senile dementia]. PMID- 8474224 TI - [Immunological study on Alzheimer's disease using anti-beta-protein monoclonal antibodies]. AB - Monoclonal antibodies (TB1 & TB2), which were obtained by immunization of 24 amino acids in BALB/c mice, bound specifically to the amyloid senile plaque and amyloid-angiopathic lesions of brain tissues of patients with Alzheimer's disease (AD) or with senile dementia of Alzheimer type (SDAT), and strongly reacted with the 1st part (Asp-Ala-Glu-Phe-Arg-His-Asp) of beta-protein. Western blotting and two-dimensional immunoelectrophoresis of cerebrospinal fluid (CSF) and serum revealed bands of 125 and 20 kilodaltons. The positive frequency of 125 and 20 KD bands detected by two-dimensional immunoelectrophoresis was higher in the serum of AD and SDAT patients (12 cases) than in that of normal control patients. ELISA employing various anti-amyloid precursor protein (APP) antibodies was performed using the extract of the human neuroblastoma cell line (NB39) which produces APP. In the near future, we hope to measure APP in CSF and sera from patients with Alzheimer's disease. PMID- 8474225 TI - [Effect of aging on sensitivity of blood pressure to salt]. AB - We investigated the correlation between aging and sensitivity of blood pressure to salt. 88 non-treated essential hypertensives were divided into four groups: less than 40 years old (n = 20), 40-49 years old (n = 20), 50-59 years old (n = 39), and greater than 60 years old (n = 11). Changes of blood pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine (PNE), and plasma epinephrine (PE) due to salt load were compared among four groups. Salt sensitivity of blood pressure was increased with aging, and there was a positive correlation between them (r = 0.30, p < 0.01). Decrement of PRA due to salt load was decreased with aging, and there was a negative correlation between them (r = -0.35, p < 0.05). PCA and PNE were suppressed by salt load, and the decrement degrees did not change with age. PE did not change by salt load. We conclude that salt sensitivity is increased with age in essential hypertensives, and renin-angiotensin system might be involved in it. PMID- 8474226 TI - [Prevalence, rate of correct clinical diagnosis and mortality of cancer in 4,894 elderly autopsy cases]. AB - The prevalence, rate of correct clinical diagnosis and mortality of cancer were analyzed in 4,894 consecutive autopsies at the Tokyo Metropolitan Geriatric Hospital from 1972 to 1990. average age and standard deviation of patients was 78.1 +/- 9.1 years. Cancer was found in 45.5% of patients of 60 years and over, and in 49.1% in men and 41.9% in women (p < 0.001). Cancer prevalence decreased with advance in age; 50.0% in the sixties, 47.9% in the seventies, 43.2% in the eighties and 39.3% in the nineties and over. Multiple cancer was found in approximately 12% of patients of 70 years and over. The top three cancer incidences were gastric cancer, 15.0%, lung cancer, 10.7% and colon cancer, 5.9% in both genders. In men, prostate cancer was next common, followed in orderly hepatic cancer, esophageal cancer, gall bladder-bile duct cancer, pancreas cancer, renal cancer and urinary bladder cancer. In women, the following order of frequency was gall bladder-bile duct cancer, uterus cancer, pancreas cancer, hepatic cancer, breast cancer, thyroid cancer, esophageal cancer, renal cancer and urinary bladder cancer. The prevalence of gastric cancer, lung cancer, hepatic cancer and esophageal cancer was significantly higher in men, while that of gall bladder-bile duct cancer was higher in women. The age-related tendencies varied among cancers of different organs. Gastric cancer increased up to the sixties in men and up to the seventies in women and leveled off after those ages. Lung cancer revealed peak prevalence in the sixties and seventies and decreased after the age of eighty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474227 TI - [Gastric emptying in elderly patients with cerebral vascular diseases and the effect of trimebutine]. AB - The authors investigated gastric emptying in 18 elderly patients with cerebral vascular diseases using the acetaminophen method. Subjects were divided into 2 groups according to their levels of daily activity. One group consisted of 10 comatose patients (71-92 years old), the other consisted of 8 patients (74-95 years old) who could walk by themselves. We also investigated gastric emptying in 6 comatose patients (38-83 years old) because of other diseases such as amyotrophic lateral sclerosis and in 11 elder controls (75-95 years old). In elderly controls, the acetaminophen concentration at 45 minutes was 9.08 +/- 1.71 micrograms/ml. In comatose patients due to cerebral vascular diseases, the concentration was 3.89 +/- 1.60 micrograms/ml, which showed significantly delayed gastric emptying (p < 0.05). In patients with cerebral vascular diseases who could walk, the concentration was 6.51 +/- 0.99 micrograms/ml. In comatose patients by another diseases, the concentration was 5.82 +/- 1.13 micrograms/ml. We suspected that delayed gastric emptying is related to the comatose state. Trimebutine significantly (p < 0.01) improved gastric emptying in comatose patients with cerebral vascular diseases. PMID- 8474228 TI - [Concentrations of multiple neurochemicals in the cerebrospinal fluid of patients with senile dementia and the relationship to alpha 1-antichymotrypsin]. AB - The authors investigated the concentrations of multiple neurochemicals (6 kinds of catecholaminergic and 5 kinds of indolaminergic substances) in the lumbar cerebrospinal fluid (CSF) of patients with and without senile dementia (13 Alzheimer type (AD), 7 vascular type (VD), 11 Parkinson's disease (PD) and 9 non demented controls (C)) by means of a neurochemical analyzing system (Neurochem, ESA). By means of the enzyme-linked immunosorbent assay (ELISA), we also determined the concentration of alpha 1-antichymotrypsin (ACT) in the CSF, which may be a possible diagnostic biochemical marker of the senile dementia of Alzheimer type. ACT in CSF was significantly higher in the AD group. It correlated negatively with Hasegawa's dementia scale (HDS) significantly. It also correlated negatively with the concentration of HVA significantly and showed tendency to correlate with the concentrations of dopamine and the ratio of kynurenine and tryptophan (KYN/TRP). Each dementia group showed characteristic concentration patterns of neurochemicals (DA, HVA, MHPG/NE, KYN/TRP, and 5-HIAA/5 HT). Our approach may provide a new quantitative method to diagnose geriatric neuropsychological diseases as well as senile dementia. PMID- 8474229 TI - [Clinical evaluation of finger blood pressure measurement devices for home-use]. AB - We evaluated the accuracy of two types of finger blood pressure (BP) measurement devices for home-use (EW276 H, NATIONAL Ltd. and HEM 804F, OMRON Ltd.) by comparing BP values with upper-arm BP measured with a standard mercury column sphygmomanometer in 28 elderly subjects (13 Hypertensives and 15 normotensives). The correlation coefficient of systolic BP value and that obtained by each method was R2 = 0.5 for EW 276H and R2 = 0.6 for HEM 804F. The higher the systolic BP, the greater was the difference between the upper-arm and finger BP values. The magnitude of the difference between finger and upper-arm values for systolic BP did not correlate with pulse wave velocity. An underestimation of the finger BP device in systolic BP was 23.8 mmHg in hypertensives and 7.6 mmHg in normotensives for the EW 276H, and 15.3 and 3.5 mmHg, respectively for the HEM 804F. This study demonstrated a large difference between the finger BP value measured with the home-use devices and upper-arm BP value measured with a standard mercury sphygmonanometer in elderly hypertensive patients. The difference may be due not only to atherosclerotic change, but also to methodological factors related to finger BP measurement. PMID- 8474230 TI - [A case of megaloblastic anemia with abnormally high urine level of beta aminoisobutyric acid]. AB - A 78-year-old man was admitted to our hospital with anemia and jaundice. Hematological studies revealed hyperchromic macrocytic anemia, and biochemical studies revealed findings of hemolysis. The folic acid level was low and megaloblasts were observed in the bone marrow. From these findings, the patient was diagnosed as having megaloblastic anemia due to folic acid deficiency. This patient had been a heavy alcohol drinker in the habit of drinking alcohol without meals. He began to eat regular meals in the hospital, and the anemia and jaundice improved gradually. Since liver cirrhosis was suspected, amino acid analysis of the urine was performed, and abnormal excretion of beta-amino-isobutyric acid (BAIB) was found. According to the amount of BAIB excreted, the Japanese population can be divided into low and high BAIB excretors comprising 65% and 36%, respectively. BAIB is also considered to reflect dissimilation of thymine. The present patient was included in the high excretion group because of the abnormally high urine level of BAIB, which was considered to be caused by ineffective hematopoiesis in the bone marrow as a result of his megaloblastic anemia. For this reason, dissimilation of thymine was considered to have been active in this patient. PMID- 8474231 TI - [Effective treatment by bifemelane hydrochloride for emotional incontinence and regional blood flow in patient with cerebral infarction]. AB - The authors report that bifermerane hydrochloride treatment improved emotional incontinence in patient with cerebral infarction. Before and after bifermerane hydrochloride treatment, 99mTc-HM PAO single photon emission CT (SPECT) was performed. After treatment, regional cerebral blood flows (CBF) in frontal lobe area increased selectively. These findings suggest that emotional incontinence and decreased CBF of the frontal lobe area were closely associated in this case. PMID- 8474232 TI - [Hyper- nd- hyponatremia in aged subjects]. PMID- 8474233 TI - Flow-cytometric characterization of cardiac allograft-infiltrating cells following MHC class I antigen pretreatment in the mouse. AB - Changes in the graft-infiltrating cell population (GIC) induced by Class I MHC pretreatment were characterized using flow cytometric analysis. C3H mice received 10(7) EL4 cells intravenously 14 days prior to transplant with C57BL/10 (H-2b) hearts. Transplanted hearts were removed from six recipients in both groups at 4, 6, 9, 12, 15, and 21 days after transplantation. GICs were harvested and incubated with FITC-conjugated Lyt-1 and Lyt-2 and phycoerythrin-conjugated L3T4 monoclonal antibodies. The proportion of GICs which were Lyt-1, L3T4, or Lyt-2 positive was similar in both control and pretreated groups at all times posttransplant, and all three cell populations exhibited similar changes over the course of the study in both groups. At Post-transplant Day (PTD) 9, there were significantly more double-staining cells (L3T4+, Lyt2+) in the pretreated group than in the control group (8.58 +/- 2.49% vs 4.36 +/- 1.32%, P < 0.05). By PTD 15, the double-staining cells had increased in pretreated mice to 17.46 +/- 4.36% of the total GICs (P < 0.05). The percentage of GICs in EL4-pretreated mice which were Lyt-1- was significantly higher at all time points than the percentage of L3T4- or Lyt-2- cells, whereas in the control, these cell populations were equivalent, implying that in pretreated mice, cells are present which are L3T4+ or Lyt2+ but Lyt-1-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474234 TI - Glutathione depletion alters hepatocellular high-energy phosphate metabolism. AB - Oxygen free radicals have recently been implicated as a major cause of tissue injury in critically ill patients. Glutathione (GSH) is a potent endogenous antioxidant that may be important in minimizing oxidant-induced organ damage. However, this tripeptide is depleted during severe illness. In order to determine the effect of GSH depletion on hepatic high-energy phosphate metabolism, in vivo 31P magnetic resonance spectroscopy was used to measure phosphate ratios in male Wistar rats given 1 ml/kg of diethylmaleate (DEM), an agent that binds and thus depletes tissue GSH, or corn oil vehicle intraperitoneally. Spectra of the liver were obtained in noninjected animals (baseline, n = 15) and in rats 2 and 24 hr after the intraperitoneal injection of DEM (n = 20) or corn oil (control, n = 20). These spectra were used to measure hepatocellular pH, phosphomonoester to ATP (PME/ATP), and phosphodiester to ATP ratios, measures of hepatocellular damage; and the inorganic phosphate (Pi)/ATP ratio, a measure of energy status. In addition, tissue GSH, phosphofructokinase, citrate synthase, and beta-OH-acyl Co-A dehydrogenase activities as well as hepatocellular ATP were measured in vitro in representative liver samples. Hepatic GSH levels were maximally depressed by 85% 2 hr after the injection of DEM (6.94 +/- 0.34 vs 0.94 +/- 0.22 microM/g wet wt, baseline vs 2 degrees DEM). This was associated with a marked increase in the PME/ATP and Pi/ATP ratios by 25 and 33%, respectively, and both ratios were significantly correlated with the severity of hepatic GSH depletion (r = 0.63, P < 0.001 and r = 0.42, P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474235 TI - Durability of the in situ bypass following modification of abnormal vein segment. AB - Modification procedures performed during in situ bypass grafting to correct an injured or inadequate saphenous vein segment result in a significant increase in the incidence of vein graft complications in the follow-up period. Modification procedures were performed in 96 in situ saphenous vein bypasses and consisted of primary closure (n = 28), vein patch angioplasty (n = 31), or resection and/or replacement (n = 37). At 4 years primary patency was 54%, secondary patency was 73%, and limb salvage was 89%. The incidence of subsequent vein graft stenosis and revision or graft failure was similar for grafts requiring vein patch angioplasty (7 of 31, 23%), primary repair (9 of 28, 32%), and resection and/or replacement (16 of 37, 43%) (p not equal to ns). Only 4 bypass revisions were performed for stenosis at the site of the original modification procedure. The type of vein graft repair did not significantly affect the primary patency at 18 months (primary closure, 65%, vein patch angioplasty, 66%, and resection and/or replacement, 58%) or the secondary patency at 30 months (primary closure, 80%, vein patch angioplasty, 90%, and resection and/or replacement, 77%). Modified autogenous conduits maintain patency and limb salvage but are prone to develop graft complications in the follow-up period. PMID- 8474236 TI - Effect of fibrin glue and opsite on open wounds in DB/DB mice. AB - Fibrin glue is a hemostatic and adhesive agent that has been used for many years in Europe. It is made by the simultaneous mixing of concentrated fibrinogen complex and bovine thrombin reconstituted in a solution of calcium chloride. Upon mixing, the final stages of the coagulation cascade are mimicked, resulting in formation of a fibrin clot. Fibrin is vital in wound healing because the network formed in the wound acts not only as a hemostatic barrier but also as a scaffold for migrating cells. In this study, fibrin glue (60 mg/ml) was applied on 6-mm diameter circular full-thickness wounds in homozygous, genetically diabetic mice. Results showed delayed wound closure as compared to paired control wounds. Dilution of the protein concentration of fibrin glue to 1 mg/ml resulted in higher histological scores compared to those for wounds treated with 60 mg/ml fibrin glue. Finally, the application of an adherent semipermeable dressing (Opsite) over the wound per se resulted in delayed wound closure. Delayed closure may be due either to mechanical obstruction to the migration or proliferation of cells that actively participate in the wound healing process, mechanical inhibition of wound contraction, or both. PMID- 8474237 TI - The ipsilateral organization of the afferent nerves to the stomach. AB - In previous nerve tracing studies we found evidence that the efferent gastric vagus nerves supplying the anterior gastric wall had a regional organization. The first part of this study aimed to determine whether vagus afferent nerve cells supplying the stomach have a regional organization; an ipsilateral pattern of innervation was found. Next, selective blockade of the afferent nerves was performed and verified by axonal tracing. Animals with afferent blockade were stressed to determine the effect of afferent nerve blockade on the gastric stress response. After selective blockade of afferent vagus nerves to the anterior gastric wall in rats, water-immersion stress was then applied. The part of the gastric wall with afferent nerve blockade had fewer acute gastric lesions than control animals or the contralateral side of the stomach after 24 hr of stress. This study supports the hypothesis that afferent as well as efferent vagus nerves have an ipsilateral arrangement. Afferent nerve blockade of the left vagus nerve protected the anterior wall of the stomach against stress ulceration. PMID- 8474238 TI - Functional evaluation of intrathoracic versus extrathoracic skeletal muscle ventricles. AB - Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 10 dogs. In Group I (n = 5), SMVs were left in an extrathoracic position on the chest wall. In Group II (n = 5), SMVs were placed within the chest cavity. After a 3- to 4-week vascular delay period, SMVs were electrically preconditioned with 2 Hz continuous stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock circulation system, and function was evaluated under differing conditions of preload and afterload. SMVs in Group II were significantly more compliant, as demonstrated by the end diastolic pressure volume relationship, than those in Group I (P < 0.01). SMVs in Group II were also capable of generating greater stroke work than those in Group I (P < 0.05). SMVs in Group II were also capable of greater stroke work than those in Group I at physiologic preloads (P < 0.05). These findings suggest that SMVs placed in an intrathoracic position exhibit better diastolic and systolic function. PMID- 8474239 TI - Influence of the timing of blood transfusion on experimental tumor growth. AB - Blood transfusion prior to renal transplantation improves subsequent renal allograft survival, and some experimental studies have shown that allogeneic transfusion significantly increases growth of subsequently transplanted tumors. The aim of the present study was to examine the influence of the timing of transfusion on tumor growth. Six experiments were performed, each with different intervals between blood transfusion and inoculation of mice with an immunogenic B16 melanoma cell line. Each experiment contained three groups of C57 BL/6J mice which received intravenously normal saline, syngeneic blood, or allogeneic blood. Allogeneic transfusion 7 and 10 days before, but not at the time of, tumor inoculation produced a significant increase in tumor growth. Allogeneic transfusion within the first 10 days after tumor inoculation was associated with larger and heavier tumors than those observed in animals treated with saline or syngeneic blood, although the differences were not always statistically significant. Multiple transfusions after tumor inoculation and transfusions in animals bearing well-established tumors significantly increased tumor growth. The study shows that growth of a transplantable immunogenic murine tumor can be increased by prior allogeneic transfusion and, perhaps more importantly, by allogeneic transfusions given after the tumor has become established. PMID- 8474240 TI - Effect of varying days of tissue plasminogen activator therapy on the prevention of postsurgical adhesions in a rabbit model. AB - The depression of focal fibrinolytic activity in mesothelial or serosal tissues which results from a surgical ischemic insult can lead to the formation of permanent fibrinous adhesions. To assess the time course for the prevention of adhesion formation by recombinant tissue plasminogen activator (rt-PA), infusions of rt-PA were administered to rabbits every 12 hr for a total of 1, 2, 4, or 8 days. Animals in each rt-PA treatment group received a total cumulative dose of 16 mg. Control animals received saline with the same corresponding dosing regimens as the treated groups. Prior to dosing, all animals had a devascularizing injury to the uterine horns performed bilaterally by bipolar cauterization of the uterine mesenteric vascular arcade below the horns. A catheter was then placed from a subcutaneous port to the intraperitoneal space. rt-PA, or saline, was instilled intraperitoneally via the subcutaneous port. Adhesions were scored at the second laparotomy by assessing the percentage of the involvement of the uterine horns in adhesions. Mean score for adhesion formation in each placebo group was 35 to 40%. Mean score (+/- standard error of the mean) for rt-PA after 1 day of therapy was 13.1% +/- 3.89; after 2 days of therapy, 6.3% +/- 1.57; after 4 days of therapy, 3.8% +/- 1.57; and after 8 days of therapy, 6.9% +/- 2.3 (P < 0.01 compared to the control grouped mean for each day of treatment).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474242 TI - Practice merging economics. PMID- 8474241 TI - Maturational differences in hepatic microhemodynamics in rats. AB - Age-related changes in the hepatic microcirculation may contribute to the increased susceptibility of the immature liver to microvascular injury. We quantified sinusoidal and acinar diameters, sinusoidal red cell velocities (VRBC), and sinusoidal volume flows to characterize microhemodynamics of weanling and adult rat livers with and without hepatic artery (HA) ligation using intravital fluorescence videomicroscopy. Despite a 20% faster heart rate and a nearly 20% lower mean arterial and portal vein pressure in weanling rats relative to those in the adults, weanling periportal and pericentral sinusoidal velocities were approximately 30 and 25% faster, respectively, than those in adults. Furthermore, the HA was found to contribute more to maintenance of sinusoidal VRBC in the immature liver as demonstrated by a significant decrease in both periportal and pericentral VRBC following HA ligation. HA ligation had no effect on VRBC of either zone in adults. Zonal volume flow (HA intact), however, was maintained independent of age. These results suggest a lower extrasinusoidal resistance in the weanling. The 25% shorter acinar diameter that we found in weanling livers likely contributes to a lower extrasinusoidal resistance by allowing a higher ratio of inflow vessels to volume of tissue. Shorter sinusoidal pathways in weanling livers also decreases sinusoidal resistance 1.3-fold relative to that in the adult, countering the approximately 1.5 times increase in resistance due to the smaller caliber of sinusoidal vessels so that overall sinusoidal resistance is not age-dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474243 TI - Anabolic steroid abuse and tooth size-arch dimensions in the rat. AB - Anabolic steroids are misused by adolescents and adults to increase muscle mass and improve appearance and athletic performance. Since anabolics strongly enhance protein synthesis, it was speculated that alterations in tooth size and arch length could occur. This study quantified the effects of the anabolic steroid nandrolone phenpropionate on these parameters in a rat model. The steroid significantly increased mandibular arch length. No difference in mesiodistal dimensions of the molars occurred. In consequence, the increased arch dimensions combined with unaltered tooth size may result in dental spacing and/or other malocclusions. PMID- 8474244 TI - The elastic and anelastic behavior of elastomeric impression materials. PMID- 8474245 TI - Ludwig's angina: historical perspective. PMID- 8474246 TI - Genetic response of microbes to extreme challenges. AB - Bacteria are capable of surviving in a wide range of seemingly impossible situations. In the main part this is because very large numbers of individual cells are involved, so that even very rare mutations will occur often enough to solve most acute problems and permit growth. But in addition, bacteria have evolved in an environment that has fluctuated so often in the past that they may have evolved a group of "last ditch" mechanisms to meet these challenges. These include developing a metabolically inactive state; activating previously evolved, but silent genes; increasing rates of mutation under dire condition; and favoring movement of exogenous and endogenous genetic elements. Some of these processes can function to make it appear that directed "Lamarckian" mutations have occurred. Together these survival mechanisms constitute the "catastrophe insurance" of the cells. PMID- 8474247 TI - Computer simulation of tumour cell invasion by a stochastic growth model. AB - The structure and function of biological systems are considered to be closely related. The present study addresses the question of how histological patterns of tumours are related to specific functional properties of the tumour cells. A mathematical model was developed, which facilitates the simulation of tumour growth and invasion by computer. The degree of cell division, migration and death can be interactively set and the simulation results can be observed on the screen. Additionally, these basic functional properties of a particular cell can be influenced by autocrine and paracrine factors. The study shows that the resulting morphological patterns closely depend on the preset functional properties of the tumour cells. Furthermore, each autocrine or paracrine factor, or combinations of these factors, induce peculiar modifications of the tumour pattern. These results provide evidence that histological tumour patterns reflect functional properties of the tumour cells and their interaction with the micro environment. Qualitative and quantitative comparison of real tumour specimens with patterns simulated by computer may thus provide a logical base for a functional interpretation of static histological images. PMID- 8474248 TI - Unequal cell division as a driving force during differentiation. AB - Unequal cell division, leading to daughter cells of different sizes, is a common event during development. We have formulated a model that shows how different cell sizes can lead to significant differences in the expression of an activator gene. The model is based on well-known aspects of the regulation of gene expression, specifically the existence of multiple regulatory sites, positive autoregulation, and the short half-life of regulatory proteins. Thus the daughter cells may follow distinct differentiation pathways even if there were no localized determinants in the mother cell. PMID- 8474249 TI - Cellular automata approaches to biological modeling. AB - We review a number of biologically motivated cellular automata (CA) that arise in models of excitable and oscillatory media, in developmental biology, in neurobiology, and in population biology. We suggest technical and theoretical arguments that permit greater speed and enhanced realism, and apply these to several classical examples of pattern formation. We also describe CA that arise in models for fibroblast aggregation, branching networks, trail following, and neuronal maps. PMID- 8474250 TI - Typogenetics: an artificial genetic system. AB - Cellular automata are now used to model various natural phenomena. In particular, they provide a logical universe in which artificial cells can be embedded in the form of propagating virtual automata. In this paper, we propose a molecular automaton which is an attempt to implement the "molecular logic of the living state" in an artificial biochemistry. This automaton is an artificial genetic system composed of two classes of interacting artificial molecules. It was shown to be self-replicating and to possess features that are analogous to those of the postulated prebiotic molecular systems. PMID- 8474251 TI - On the mechanism of long chain fatty acid transport in cardiomyocytes as facilitated by cytoplasmic fatty acid-binding protein. AB - Fatty acid-binding protein (FABP) is abundantly present in the cytoplasm of the cardiomyocyte, i.e. the cell which causes the contractile activity of the heart. Although FABP is thought to act as an intracellular long chain fatty acid (FA) carrier, definite experimental proof on this putative function has yet to be obtained. In the present study, experimental results from several authors were combined in an attempt to elucidate the precise physiological function of heart type FABP in cardiac FA transport. It was calculated that, under normal conditions, the major part of FA in the cardiomyocyte is dissolved in lipid bilayers and that the presence of FABP in the heart enhances the aqueous solubility of FA more than 700-fold despite the fact that only a minor part (< 2%) of the total FABP content is then complexed with FA. Moreover, it is shown that, as a result of the enhanced cytoplasmic solubility, the FA flux from sarcolemma (the cellular membrane of the cardiomyocyte) to mitochondria is increased at least 17-fold in the presence of physiological amounts of FABP compared with the hypothetical situation in which FABP is absent. These calculations indicate the involvement of FABP in the transport of FA from the sarcolemma to those mitochondria lying in the innermost region of the cardiomyocyte. The extent to which FABP facilitates FA trafficking through the cytoplasm of the cardiomyocyte under physiological circumstances remains, however, to be established. PMID- 8474252 TI - An hypothesis for the periodicity of smallpox epidemics as revealed by time series analysis. AB - Parish registers have been studied by time series analysis to detect smallpox epidemics in England during 1600-1800. Confirmatory evidence was provided by the seasonality of child mortality. A 5-year cycle in smallpox epidemics was detected in medium-sized, rural towns. Consideration of the mathematics of the dynamics of viral diseases suggests that the true interepidemic period where smallpox is endemic should be 2-3 years and it is concluded that, in the towns studied, the disease was not endemic but that the oscillations were established by 5-year cycles of periods of famine associated with high wheat prices. The cross correlation function between the two cycles shows zero lag and the input-output function shows significant coherence. Another epidemic follows only when a sufficient density of susceptibles has been established by births, so that the cycles become phase-locked. It is predicted that smallpox (i) was endemic in London and other large cities, with 2-3 year epidemics, (ii) was epidemic with a 5-year oscillation in rural towns, (iii) did not reach epidemic proportions in scattered communities. PMID- 8474253 TI - Does HIV "piggyback" on CD4-like surface proteins of sperm, viruses, and bacteria? Implications for co-transmission, cellular tropism and the induction of autoimmunity in AIDS. AB - Coinfections of human immunodeficiency virus (HIV), EBV, and HTLV or sperm proteins act synergistically to enhance infectivity and replication and expand cellular tropism. While some aspects of these synergisms are understood, others are not. We have found that membrane or surface proteins of CMV, HTLV, EBV and sperm proteins share large regions of similarity with the CD4 protein of T-helper lymphocytes. Since HIV uses CD4 as a receptor, it may bind to CD4 homologues on CMV, HTLV, EBV or sperm proteins. HIV could then "piggyback" with these viruses into cells with which it normally has no tropism. Similarly, HIV may expand the cellular tropism of CMV, or EBV. Such a piggyback mechanism may provide insight into the formation or presentation of CD4-like antigens from CMV, HTLV, EBV and sperm proteins with class II MHC-like antigens on HIV (gp160 and Nef proteins) and may break immunological tolerance, inducing the autoimmunity observed against both CD4+ and class II MHC+ T cells in AIDS patients. PMID- 8474254 TI - In vitro movement of actin filaments over myosin: role of actin and related problems. PMID- 8474255 TI - Determination of neuronal number and process surface area in organotypic cultures: a stereological approach. AB - Preparation of nervous tissue as an organotypic culture permits examination of nervous system development and interactions between neurons and with their environment. In order to evaluate the statistical significance of morphological changes, it is necessary to quantify tissue populations and parameters. Recent advances in stereology facilitate the gathering of morphometric data, while eliminating sources of error associated with traditional methods. Unfortunately, the new stereology has been perceived as complex and, therefore, has been slow to gain acceptance within neuroscience investigations in general and in vitro applications in particular. Here, we present a detailed application of the new, unbiased stereology to organotypic hippocampal cultures. These methods allow assessment of neuronal survival and morphological plasticity to culture conditions with increasing culture age. Neuronal number was assessed from point sampled intercepts of cells sampled without bias by the selector procedure in vertical sections through hippocampal cultures. Surface area was estimated from profile intersects of neuronal processes with a cycloid array. The reference volume was determined by the Cavalieri method; this permitted expression of results as absolute values rather than as component densities. The importance of absolute values to valid interpretation of quantitative data is demonstrated by the results for neuronal number. The methods applied here provide a powerful approach to quantitation of organotypic cultures, and represent an important extension of qualitative studies of cultured nervous tissue. PMID- 8474256 TI - A one-step immunohistochemical method for detection of blood-brain barrier disturbances for immunoglobulins in lesioned rat brain with special reference to false-positive labelling in immunohistochemistry. AB - Disturbances of the blood-brain barrier (BBB) following brain lesions lead to extravasation of serum proteins that can be detected by immunohistochemical methods in tissue sections. Here, extravasated immunoglobulins were visualized by a 1-step technique using rabbit anti-rat immunoglobulins conjugated to horseradish peroxidase (HRP). This method is associated with a lower background staining than the conventional 3-step peroxidase-antiperoxidase (PAP) technique using rabbit antibodies against rat whole-serum proteins or immunoglobulins (IgG). Further tests using a direct conjugate of rabbit anti-rat immunoglobulins to fluorescein isothiocyanate (FITC) showed usefulness of the approach for fluorescence microscopy. Additional experiments showed that antibodies directed against mouse immunoglobulins as used for detection of mouse monoclonal antibodies can cross-react with extravasated rat immunoglobulins. Therefore, immunohistochemical studies on lesioned rat brain should routinely include a visualization of areas containing extravasated serum proteins including immunoglobulins. PMID- 8474257 TI - A tactile stimulator for studying motion processing in the somatic sensory system of primates. AB - A tactile stimulator was built for studying motion processing in the somatic sensory system of primates. This stimulator is used for assessing the responses of neurons of the somatic sensory system to stimuli moving in any traverse distance (range: 2-20 mm), with a variety of velocities (range: 4-120 mm/s), forces (range: 0-60 gf), and in any scanning direction. The stimulator is highly automated and can be used in combined psychophysical and neurophysiological studies in humans and in behaving monkeys. PMID- 8474258 TI - A low-cost VGA-based visual stimulus generation and control system. AB - A flexible visual stimulus system has been developed for neuroscience research that uses low-cost and widely available personal computer hardware. The system has many advantages over those that rely upon traditional optical and mechanical methods, including size, flexibility and spatiotemporal resolution. The system is designed around an IBM-compatible personal computer, equipped with a VGA graphics card and a VGA monitor or projector. A set of assembly language routines has been developed for the setup and control of the graphics hardware so that images are generated and then moved with single pixel/single frame resolution. Two variations of this system are described. One version enables a stimulus on the display monitor to be imaged directly on the retina in vitro during spike recordings; the other variant back-projects an image onto a tangential screen for in vivo testing in the awake animal. Using the latter approach, the image can be positioned on the retina as the eye continues to move. PMID- 8474259 TI - Reduced compartmental models of neocortical pyramidal cells. AB - Model neurons composed of hundreds of compartments are currently used for studying phenomena at the level of the single cell. Large network simulations require a simplified model of a single neuron that retains the electrotonic and synaptic integrative properties of the real cell. We introduce a method for reducing the number of compartments of neocortical pyramidal neuron models (from 400 to 8-9 compartments) through a simple collapsing method based on conserving the axial resistance rather than on the surface area of the dendritic tree. The reduced models retain the general morphology of the pyramidal cells on which they are based, allowing accurate positioning of synaptic inputs and ionic conductances on individual model cells, as well as construction of spatially accurate network models. The reduced models run significantly faster than the full models, yet faithfully reproduce their electrical responses. PMID- 8474260 TI - Correction for the influence of background muscle activity on stretch reflex amplitudes. AB - Background muscle activity (BGR) exerts a strong influence on stretch reflex amplitudes. While it is considered important to correct for this influence, which method best able to eliminate the effects of BGR remains unknown. We have therefore compared one previously described and one novel correction method which respectively consisted of calculating (1) the difference between reflex amplitude and BGR, and (2) the ratio of reflex amplitude to BGR. These correction methods were evaluated in a group of 23 healthy individuals. BGR and stretch reflexes were recorded from the gastrocnemius muscle of standing subjects who received sudden toe-up perturbations of a supporting platform upon which they were standing. Calculation of differences markedly reduced the influence of BGR on stretch reflex amplitudes in most, although not all, subjects. Calculation of ratios failed to correct for BGR in most subjects and caused a net increase in the influence of BGR on stretch reflex amplitudes. Because both correction methods insufficiently corrected for BGR in normal subjects, we introduce the use of analysis of covariance (ANCOVA) to reliably remove the influence of BGR on stretch reflex amplitudes. The use of ANCOVA is exemplified by showing that stretch reflex amplitudes are enhanced in patients with Parkinson's disease even if the influence of high BGR is completely taken into account. PMID- 8474261 TI - Real-time imaging of neurons retrogradely and anterogradely labelled with calcium sensitive dyes. AB - Membrane-impermeant calcium indicator dyes were used to retrogradely label dorsal root ganglia, spinal motoneurons and interneurons in the spinal cord of the chick embryo. The dyes were also used to label anterogradely primary afferent axons in the spinal cord and synaptic endings in the ciliary ganglion. Labelled neurons were imaged using digital videomicroscopy. Motoneurons and dorsal root ganglion cells exhibited a frequency-dependent change in fluorescence during antidromic stimulation. Single antidromic stimuli resulted in fluorescence transients that could be resolved in individual cells in real time. In addition, fluorescence changes could be recorded in motoneurons during episodes of bursting generated by rhythmic synaptic inputs from premotor networks. Stimulus-induced fluorescence signals were also detected in axons and synaptic endings labelled anterogradely. Optical signals were largely abolished in the absence of extracellular calcium. The results show that calcium changes can now be measured in identified populations of neurons and presynaptic terminals. The strong dependence of these signals on impulse activity suggests that the technique will be useful for monitoring the activity of identified neuronal populations. The calcium-dependent fluorescence signal probably results from cytosolic dye derived from diffusion which may limit the technique to situations in which the dye can be applied close (< 1 cm) to cell bodies. PMID- 8474262 TI - Mayo legal department. PMID- 8474263 TI - Multidimensional visualization in echocardiography: an introduction. AB - X-ray films depict three-dimensional objects as shadows in a two-dimensional plane; thus, objects become superimposed. Computed tomography and other types of tomographic imaging, such as ultrasonography, acquire two-dimensional images of a material property within a thin slice. Sequential adjacent two-dimensional tomograms can be used to construct three-dimensional displays of objects. Visualization, a field of computer science, enables scientists to measure image attributes (extraction of features), identify features (classification), separate objects from one another (segmentation), and produce comprehensible, information dense images from three-dimensional data sets (rendering). A three-dimensional rendering of the heart can be used to represent only one component of the heart, such as the atrial septum or the ventricular chamber, and can be shaded or colored to enhance comprehension. Three-dimensional images rendered sequentially over time result in a dynamic four-dimensional display. This report describes multidimensional visualization of objects and tissues and specifically discusses examples from echocardiography. PMID- 8474264 TI - Three- and four-dimensional cardiovascular ultrasound imaging: a new era for echocardiography. AB - Three-dimensional and four-dimensional ultrasonography were pioneered in the 1960s yet have been used little clinically. Only recently have advances in cardiovascular ultrasound equipment and in digital image storage, manipulation, and display techniques made three- and four-dimensional imaging clinically feasible. In this report, we review the historical development of these technologies during 3 decades to their culmination in current state-of-the-art technology. Examples of such multidimensional images are presented, with special emphasis on clinical applications. Although several limitations persist, three dimensional cardiovascular ultrasonography seems likely to enhance imaging of the heart and vessels in a manner similar to the advent of two-dimensional echocardiography in the M-mode era. Clinician-scientists will soon be able to extract an object, such as the heart, from the body electronically for the purpose of anatomic, functional, and histologic analysis without adverse effect on the patient. PMID- 8474265 TI - Urolithiasis in pediatric patients. AB - Urolithiasis in pediatric patients has been perceived as uncommon, and the appropriate evaluation and management have been controversial. To determine the clinical characteristics, types of stone problems, and outcomes of pediatric patients with urolithiasis encountered in a referral center, we retrospectively assessed 221 patients (113 girls and 108 boys) with urolithiasis examined at the Mayo Clinic between 1965 and 1987. The median age at onset of symptoms was 11 6/12 years among the female patients and 10 6/12 years among the male patients. Analysis of stone constituents in 122 patients showed the proportion of calcium oxalate (44.7%), calcium phosphate (23.6%), and cystine (8.1%) stones to be similar in all age-groups. Overall, struvite stones were found in 17.1% and uric acid stones in 1.6% of patients. Conditions that predisposed to metabolic urolithiasis were identified in 115 patients (52%). Hypercalciuria was confirmed in 49 of 145 patients (33.8%) and hyperoxaluria in 25 of 124 (20.2%). Eight of 96 patients had hyperuricosuria, and 5 of 54 had hypocitraturia. Forty-one patients (18.6%) had infection-related stones. Of 66 patients with structural anomalies of the genitourinary tract, 24 (36%) had metabolic abnormalities and 26 (39%) had chronic infection. Among patients with chronic infection, 29% had metabolic abnormalities. Of the 221 patients, 148 (67%) had two or more stones during a mean follow-up of 59 months. Among 140 patients with 12 months or more of follow up, metabolic activity was present in 31 (22.1%) at the time of most recent examination. Overall, 166 of 221 children (75.1%) were found to have factors that predisposed to urolithiasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474266 TI - Phlebotomy--a minimalist approach. AB - For each patient, laboratories usually collect more blood than is needed for specific determinations. We reviewed the amount of blood collected for laboratory measurements for an entire hospital stay of 113 patients admitted during a 1-week period to a medical ward or to a medical intensive-care unit in our tertiary-care facility. The amount of blood obtained was also compared with the minimal amount needed for analysis for 18 of the most frequently ordered laboratory tests in our facility. For routine collections, a mean of 45 times the required volume of specimen (range, 2 to 102 times) was obtained. For optimal utilization of laboratory services, both the positive and the negative consequences of testing must be thoughtfully considered. Two potential adverse effects of withdrawal of blood for laboratory determinations are iatrogenic anemia and infection. Moreover, the cost of care is increased with additional analyses. Practical strategies for decreasing the amount of blood collected include an increased awareness of ordering practices, a thorough knowledge of the volume of blood needed for each laboratory test, experienced phlebotomy personnel, storage of blood specimens for potential subsequent use, and communication of accurate minimal volumes needed for specific measurements. PMID- 8474267 TI - The differential diagnosis of orbital calcification as detected on computed tomographic scans. AB - We reviewed 350 orbital computed tomographic scans to determine the frequency, significance, and differential diagnosis of calcified lesions. Of 171 suitable scans that fulfilled the study criteria, 37 (22%) showed calcific densities. The most common intraocular lesion that contained calcium was retinoblastoma, and the most frequently calcified extraocular masses were vascular lesions (hemangioma, lymphangioma, and varix). We describe two orbital tumors--metastatic colonic carcinoma and primary orbital malignant melanoma--that previously have not been reported as having calcification. The presence of calcification within lesions of the lacrimal gland fossa usually, but not always, portends malignant disease. PMID- 8474268 TI - Sir Bernard Katz--winner of Nobel Prize in physiology or medicine. PMID- 8474269 TI - Liver biopsy diagnosis of homozygous hemochromatosis: a diagnostic algorithm. AB - The diagnosis of homozygous hemochromatosis (HH) should be based on appropriate findings on liver biopsy specimens. In cases with equivocal morphologic features, quantitative tissue iron determination and calculation of the hepatic iron index generally enable one to distinguish HH from other types of hepatic iron overload. In this article, we describe a diagnostic algorithm that is designed to avoid diagnostic errors because of histologic misinterpretation or erroneous, usually false-negative, chemical iron studies. The algorithm also delineates a cost effective method of using quantitative tissue iron analysis. Diagnostic biopsy features of uncomplicated HH include (1) hemosiderosis that involves primarily hepatocytes, with or without inactive cirrhosis, and (2) a tissue iron index of 1.9 or higher. Findings such as prominent fatty changes or lymphocytic piecemeal necrosis indicate the presence of HH in conjunction with another complicating condition or secondary iron overload in the absence of HH. PMID- 8474270 TI - Digital embolization from plaque-related thrombus in the thoracic aorta: identification with transesophageal echocardiography and resolution with warfarin therapy. AB - A 71-year-old man had painful blue toes after an episode of protracted vomiting. Abdominal, cardiac, and transesophageal ultrasound studies were performed before angiography was considered. A large mobile mass in the proximal descending thoracic aorta, which suggested thrombus, was identified by transesophageal echocardiography. With no further evaluation, anticoagulant therapy with heparin and warfarin was initiated. Three months later, repeated transesophageal echocardiography demonstrated only a tiny vestige of the plaque-related mass. The pain and discoloration of the toes resolved completely. The advantages and disadvantages of the various diagnostic and therapeutic approaches to peripheral embolization are discussed. PMID- 8474271 TI - Clinical manifestations of lung cancer. AB - The initial clinical manifestations of lung cancer are diverse and may occur with or without symptoms. Manifestations of pulmonary malignant lesions are produced by local growth or invasion, metastatic disease, or paraneoplastic processes. Patterns of local invasion such as Pancoast's syndrome or the superior vena cava syndrome are relatively uncommon but well recognized. Metastatic lung cancer can involve almost any anatomic area by hematogenous, lymphatic, or, occasionally, interalveolar dissemination. Complications related to malnutrition, infection, electrolyte disturbances, and coexisting diseases influence the initial manifestations. Although individual tumor cell types are associated with characteristic features, no constellation of findings is pathognomonic for a specific histologic variant. Because successful treatment of pulmonary carcinoma depends on early detection, awareness of the typical clinical manifestations is important. PMID- 8474272 TI - Paraneoplastic syndromes associated with lung cancer. AB - Paraneoplastic phenomena associated with primary lung cancer have diverse initial manifestations and epitomize the systemic nature of human malignant disease. The spectrum of clinical features in patients with paraneoplastic syndromes ranges from mild systemic or cutaneous disease to hypercoagulability and severe neuromyopathic disorders. Although the diagnosis is often one of exclusion, an improved understanding of the pathogenesis involved in some of these syndromes has provided another means of recognizing the disorders and perhaps treating the affected patients. Proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators such as hormones and hormone-like peptides, cytokines, and antibodies. In this update, we review the potential mechanisms, diagnosis, and treatment of paraneoplastic syndromes associated with lung cancer. PMID- 8474273 TI - Diagnostic tests for lung cancer. AB - The goals of diagnostic testing in patients with suspected lung cancer are to establish the diagnosis and to determine the stage of the disease so that appropriate therapy can be initiated. Unless a patient has hemoptysis, fever, or a change in cough as an initial manifestation, resectable lung cancer will seldom be diagnosed on the basis of the history. Screening tests--particularly chest roentgenography--have usually identified the abnormality. The managing physician should then select diagnostic procedures that are associated with low risk and that will provide further diagnostic and staging information. A biopsy will almost always be necessary before definitive therapy can be planned. In many cases, a single procedure--for example, a needle biopsy of a hepatic lesion or biopsy of a supraclavicular lymph node--will provide a definitive diagnosis and establish the stage of the disease. The roles of cytology, histopathologic examination, radiologic studies, and various types of biopsy in the diagnosis of lung cancer are reviewed in this report. PMID- 8474274 TI - High-resolution computed tomography for obliterative bronchiolitis. PMID- 8474275 TI - Three-dimensional echocardiographic reconstruction: from "ice-pick" view to virtual reality. PMID- 8474276 TI - Importance of metabolic contributions to urolithiasis in pediatric patients. PMID- 8474277 TI - [Epidemiology of traveler's diarrhea in Spanish tourists travelling in developing countries]. AB - BACKGROUND: Travellers' diarrhea (TD) is the most frequent problem in travellers going to the developing countries. This paper analyses the prevalence of the syndrome by geographical areas as well as the risk factors in 2209 Spanish travellers to 3 continents. METHODS: Epidemiological data were gathered through a personnel interview filled by the travellers during their return trip. Those were introduce in a DbaseIII plus computer program and were evaluated through the Epi Info program. RESULTS: The overall prevalence of TD found was 41%. The Indian subcontinent, the Middle East and Moghreb countries showed a higher prevalence of TD. Trekkers and people on boat cruises (Nile and Amazon) had the highest prevalence of TD. The consumption of non-carbonic drinks and ice creams was significantly associated to TD. Travellers with previous gastrointestinal illnesses suffered more TD than others. CONCLUSIONS: Despite the fact that Spain in considered an area of intermediate risk for TD we found no significant differences in the prevalence of TD in Spanish travellers when compared with other published series from developed countries. PMID- 8474278 TI - [Clinical efficacy and tolerance to acarbose in the treatment of non-insulin dependent diabetic patients]. AB - BACKGROUND: Acarbose is a pseudotetrasacaride which reversibly and competitively inhibits the intestinal alpha-glycosidases leading to a decrease in the increase of postprandial glycemia. METHODS: A multicentric double-blind clinical trial (8 centers), controlled versus placebo, crossover and randomized was carried out in 90 non insulin dependent diabetic patients under treatment with diet or with diet and sulphonilureas. During the first three months of the trial the patients received placebo or acarbose randomly. Following one months of wash-out with placebo the patients received the inverse medication for 3 more months. During the first month of each phase the patients received 3 x 50 mg/day of acarbose or placebo and the following 2 months 3 x 100 mg/day. RESULTS: Upon comparison of the two treatments significant statistical differences were observed in HbA1 (p = 0.0115) and in postprandial glycemia (p = 0.0001). There were differences, although not significant, in the levels of triglycerides, cholesterol, fasting glycemia, and postprandial insulinemia. Episodes of hypoglycemia appeared in 12 patients and 57 patients referred undesirable gastrointestinal effects. CONCLUSIONS: The results of this trial indicate that acarbose may be useful in the treatment of non insulindependent diabetic patients since it significantly reduces the amount of postprandial glycemia and HbA1. PMID- 8474279 TI - [Prospective payment per case and length of stay at coordinated private hospitals]. AB - BACKGROUND: In 1991 the Valencian Health Service (SVS) introduced a system of prospective payment per process to reimburse some surgical interventions to coordinated private hospitals which, until then, had invoiced by retrospective payment per hospital stay. The impact of this change on the mean length of stay in seven groups of surgical interventions is evaluated. METHODS: Retrospective analysis of the mean stay of 2025 admissions in private hospitals coordinated under both systems of payment (payment per process 66%, October 91 to February 92; payment by stay 64%, March 91 to February 92) for seven groups of surgical procedures: cataract surgery, cholecystectomy, hernioraphy, prostate resection, tonsillectomy-adenoidectomy, varicose vein and proctologic procedures was carried out. RESULTS: Mean hospital stay decreased (mean = 5.4 days; p < 0.001) in all the groups reimbursed under PRP (from 72% in proctologic conditions to 43% for adenoidectomy-tonsillectomy) avoiding 8727 stays. The coinciding period under both systems demonstrated a decrease of mean hospital stay similar to the total period. CONCLUSIONS: The coordinated hospitals demonstrated a surprisingly rapid capacity to modify their organizative behaviour or influence the styles of clinical practice or both to adopt the patterns of length of stay which optimize profits according to the system of payment used by the SVS. PMID- 8474280 TI - [Rehabilitation in rheumatism. Purpose and reality]. PMID- 8474281 TI - [Indications for surgery in lumbar herniated disk]. PMID- 8474282 TI - [Unilateral lung transplantation: the first 2 cases. Group of Lung Transplantation of the University General Hospital of the Vall d'Hebron]. AB - Since 1983 unilateral lung transplantation has become a clinical reality. The initial experience of the Hospital General Universitario de la Vall d'Hebron is presented with the description of the two first unipulmonary transplants. The first was a 20 year-old woman with idiopathic pulmonary fibrosis in whom a left unipulmonary transplant was carried out and who, at present is at home following the 23rd postoperative month. The second case was a 27 year-old man with pneumoconiosis who, at 12 months following the left lung transplantation, carries on a normal life. Among the complications observed, the presence of pneumonitis by cytomegalovirus in both patients is of note. Stenosis and partial dehiscence of the bronchial suture in the first patient and isolation of syncitial respiratory virus in the second patient were also observed. The effort and integration into a normal life style of the second patient is excellent. In contrast, the first patient presents an important postoperative functional deterioration secondary to her complications. The present study demonstrates that unipulmonary transplantations is a reality in Spain which must be considered by all respiratory disease specialists in their daily clinical practise. PMID- 8474283 TI - [Treatment of chronic persistent severe asthma: role of methotrexate]. PMID- 8474284 TI - [New trends in the definition and diagnostic criteria of polycystic ovary syndrome]. PMID- 8474285 TI - [Fulminant meningococcemia treated with antiendotoxin IgM monoclonal antibodies (HA-1A)]. PMID- 8474286 TI - [POEMS syndrome with recurrent and multiple involvement of cranial nerves]. PMID- 8474287 TI - [The health-care and economic importance of the mean hospital stay]. PMID- 8474288 TI - [Thymoma and muscular involvement. Differential diagnosis between polymyositis and myasthenia gravis]. PMID- 8474289 TI - [Unusual presentation of Streptococcus bovis endocarditis]. PMID- 8474290 TI - [Vertebral osteomyelitis caused by Streptococcus agalactiae]. PMID- 8474291 TI - [Pancreatic pseudocysts after blunt abdominal trauma]. AB - Pancreatic pseudocyst caused by trauma is rare. Only in 5 of 98 patients on whom we operated between 1977 and 1991 for pancreatic pseudocyst were we able to detect previous blunt abdominal trauma. In a 4-year-old girl just a slight abdominal trauma had given rise to a cyst, while in 2 other patients (aged 9 and 26 years) pancreatitis occurred after trauma that was treated medically. Two patients had to undergo laparotomy immediately after suffering serious abdominal blunt injury. Diagnosis was established sonographically, except in one case, in which a large cyst was determined to originate from the pancreas, but only intraoperatively. The time-span between trauma and treatment of the pseudocyst ranged from 3 months to 1 year. Thus, continuous percutaneous suction, which is basically considered a promising therapy for cysts in their early stages of development, was obviously not feasible in our patients. We therefore carried out cysto-jejunostomy with formation of a Roux-en-Y jejunum loop. At follow up 1-10 years after operation, all patients were asymptomatic and no cyst formation could be detected sonographically. PMID- 8474292 TI - [100 years of Braun anastomosis]. AB - Although in his time a well-known and high esteemed surgeon, the data of Heinrich Braun's life are nearly forgotten, but his (now 100 year old) description of enteroanastomosis as a routine addition to gastroenterostomia made his name immortal. The author himself was not too enthusiastic about his idea, because he applied the new technique only to a few patients suffering from inoperable cancer. Apparently he never thought of the possibility nor expected the great success of the combination with the Billroth II operation as it is practised nowadays. PMID- 8474293 TI - [Extended resection of liver metastases in colorectal cancer]. AB - Over a 10-year period, 166 patients underwent liver resection with curative intent for colorectal secondaries. These included 23 (13.8%) with metastases invading to adjacent organs. Diaphragm (n = 9), major omentum (n = 5), portal vein/inferior vena cava (n = 3), gallbladder/extrahepatic biliary system (n = 3), right adrenal gland (n = 2), and lymph nodes of the hepatoduodenal ligament (n = 1) were resected en bloc together with the metastases. Operative mortality was 4.3% (1/23 patients). Intraoperative findings and the pathologist's report led to the performance of R0 resection in 14 patients, and microscopic residual disease after R1 resection was found in 7 patients; in 2 cases macroscopically visible tumour had to be left behind. Median survival for all patients was 14 months and was significantly less favourable than in patients who had undergone resection of metastases confined to the liver (P = 0.011, long-rank test). The median recurrence-free interval was 6.8 months (P = 0.11). Obviously, patients who had undergone R0 resection and whose CEA serum levels returned to normal after operation benefited the most, and among these a median survival of 17 months was recorded. It is concluded that in patients with liver metastases from colorectal cancer, invasion of the metastases to adjacent organs has significant implications for the prognosis, even if the metastases are resected. It is important to detect this situation preoperatively, to avoid subjecting patients to a treatment that offers little benefit. PMID- 8474294 TI - [Radioimmunoscintimetry for intraoperative lymph node diagnosis in colorectal cancer]. AB - In a prospective study 32 patients with primary colorectal carcinomas were studied by means of radioimmunoscintigraphy with the anti-carcinoembryonic antigen monoclonal antibody BW 431/26 labelled with either 131I (group 1, n = 17) or 99Tc (group 2, n = 15). Scintigraphy of the resected specimen was used as a model for intraoperative radioimmunoscintimetry, and all positive lymph nodes were marked during the investigation. The results were compared with the data yielded by preoperative investigations (CT, MR, endosonography) and checked by histology and immunohistochemistry. The analysis (sensitivity, specificity) included: type of investigation, time interval from antigen application, type of radionuclide, size of lymph nodes investigated, and serum level of CEA. 131I Scintigraphy of the resected specimen gave the best results in the detection of lymph node metastases (sensitivity 1, specificity 0.57) and was superior to all other diagnostic procedures. When the investigation was performed 6-8 days after administration of the antibody the specificity improved to 1. The best results (sensitivity 1, specificity 0.91) were achieved in small (< 1 cm) lymph node metastases. A good correlation between scintigraphic diagnosis and immunohistochemical CEA detection was confirmed. Serum levels of CEA had no influence on the scintigraphic results. We conclude that intraoperative radioimmunodetection of lymph node metastases may improve the radicality in the resection of colorectal tumors. The best results are achieved with 131I-labelling and with application of the antibody 6-8 days before the operation. PMID- 8474295 TI - [Surgical therapy of secondary hyperparathyroidism after kidney transplantation]. AB - Between April 1986 and January 1992, a total of 22 patients with chronic renal failure were operated on for secondary hyperparathyroidism after kidney transplantation, and 21 of these patients were normocalcemic postoperatively. In 1 patient three reductions of autotransplanted parathyroid tissue were performed and this patient was still hypercalcemic postoperatively, with a serum calcium of 2.65 mmol/l. The renal function was not impaired by parathyroidectomy. In 9 of the 22 patients subtotal parathyroidectomy was indicated within 4 months after renal transplantation because of serum calcium levels over 3.0 mmol/l or severe clinical symptoms. Subtotal parathyroidectomy is indicated in patients with secondary hyperparathyroidism after renal transplantation with a serum calcium over 3.0 mmol/l and severe clinical symptoms and also in patients with slightly elevated serum calcium levels after an observation period of up to 12 months. PMID- 8474296 TI - [Do nicotine and alcohol abuse effect the occurrence of postoperative bacterial infections?]. AB - In a prospective study we evaluated patients with diagnoses of (1) inguinal hernia (n = 57), (2) gall bladder stones (n = 80), and (3) carcinoma of the colon (n = 76). The whole group included 213 patients who underwent clean, clean contaminated or contaminated operations. All wound infections and postoperative bacterial infections such as pneumonia or urinary infection, were recorded. The patients were asked for risk factors at the time of hospitalization: 7.1% of all patients admitted an intake of alcohol of more than 60 g/day, and 15.6% of the patients smoked more than 20 cigarettes/day. We found a four times higher risk of postoperative infection for patients with an intake of more than 60 g alcohol/day. The rate of infection for smokers of more than 20 cigarettes/day is twice as high as for non-smokers or persons who smoke fewer than 20 cigarettes/day. PMID- 8474297 TI - [Therapy of advanced stomach cancer: multivisceral or multimodal?]. PMID- 8474298 TI - [Orthotopic liver transplantation in the rat]. PMID- 8474299 TI - [Orthotopic liver transplantation with arterial re-anastomosis in the rat--a detailed description of technique and analysis of possible errors]. AB - Liver transplantation (LTX) in the rat is a frequently used transplantation model. In the present study we give a detailed description of the suture technique for all anastomoses, except the bile duct, with arterialization of the transplanted liver over an aortoceliac segment to the recipient's aorta. Using this technique, we finally achieved survival rates of 80%. During the development stages, the main cause of death was an exceedingly long anhepatic time (> 20 min); later on, complications occurred only from insufficient anastomoses. The advantage of the suture technique over the cuff technique is that a more physiological anastomosis is obtained with less trauma to the recipient when using rearterialization. Despite the complicated suture technique, the anhepatic time can be well reduced to below 20 min. PMID- 8474300 TI - [Clinical and functional results of abdominal rectopexy using different fixation principles]. AB - We report our results with abdominal rectopexy (modified Ripstein procedure, Ripstein/Corman) without resection of the colon in 63 patients using lyophylized dura-strips, Vicryl gauze or Dexon gauze, as the underlying fixation material for the mobilized rectum, presacral fascia and fixation suture material. Forty-five of 64 patients (71.4%) were reevaluated by proctoscopic examination and questioning; the mean follow-up time was 52.5 months (range 3-136 months). Postoperative mortality due to the method was 0%; the mortality was 1.6% (n = 1/63) in general for the first postoperative 30-day period as a result of cardiac complications. There were three complications (4.7%) the durating operation. Postoperative morbidity was 25.4% (16/63); infectious complications occurred in 12.7% (8/63) of cases, with one case of spontaneous closure of a pelvicutaneous fistula after intraoperative injury to the rectal wall. Full-thickness rectal prolapse appeared after rectopexy in 4.4% (2/45) (dura material alone) and mucosal prolapse was seen in 15.5% (7/45) of the follow-up group. Constipation was reduced by 28.6% (18/63) to 22.2% during the follow-up. Seventeen of 28 patients (60.7%) with incontinence showed an improvement; total continence was registered in 35.7% (10/28). The increase in continence as a result of abdominal rectopexy was significant (Wilcoxon, P = 0.05). The special aspects of being in an older age group, having a long history of procidentia, the number of deliveries, the length of the preoperative incontinence period all showed no influence on the postoperative degree of continence (Spearman's rank correlation). In 7/15 cases with persisting incontinence after rectopexy, postanal repair (Parks) was efficient in 7/7 cases leading to total or partial continence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474301 TI - [Value of abdominal rectopexy in obstructive disorders of defecation. A prospective study using a defecation index, manometry and radiology]. AB - A prospective clinical, manometric, electromyographic and radiological study was conducted to judge the degree of success achieved with anterior-posterior rectopexy in 18 female patients suffering from obstructed defecation and varying degrees of incontinence. Prior to being operated on, 6 of the patients showed symptoms of intussusception, 4 an internal prolapse of the anterior rectum wall, and 5 a rectocele at least 2 cm in size; all of them had significant perianal descent. The main aim of this study was more precise definition of the pre- and postoperative bowel evacuation using a defecation index. This study shows that obstructed defecation is significantly associated with a lasting feeling of needing to defecate after evacuation, a sensation of incomplete evacuation, perianal pain and necessity for manual support during defecation. The patients had a mean age of 62 (range, 38-78) years. All underwent anterior-posterior rectopexy (Ivalon or Vicryl) with posterior pelvic repair of the puborectalis muscle. In 2 patients rectopexy was combined with sigmoidectomy, in 11 cases, with left hemicolectomy, and in 2, with subtotal colectomy. The median follow-up was 40.8 months (range, 6-66 months). Postoperatively anorectal manometry showed a significant increase in the resting anal pressure and the maximum voluntary pressure (P = 0.05). Continence was improved in 10 patients (55%), 7 (39%) of whom regained normal continence. No significant change in pelvic descent or anorectal angle was observed. Only 8 patients reported a complete evacuation of the rectum postoperatively. PMID- 8474302 TI - [Order in the chaos of classifications of erosions of the gastric mucosa]. PMID- 8474303 TI - [Thyrotropin releasing hormone: functions and importance in the gastrointestinal tract and pancreas]. AB - Thyrotropin-Releasing Hormone (TRH) was found in the last years to be localised also in the gastrointestinal tract and specially in endocrine pancreas. In the present review the results from studies concerning the function and the perspective of a clinical application of TRH in gastrointestinal diseases shall be presented. PMID- 8474304 TI - [Treatment of intraperitoneal abscess--ultrasound controlled percutaneous or surgical drainage?]. AB - In a retrospective study the effectiveness of ultrasound guided percutaneous drainage (n = 36) was compared with that of surgery (n = 38) in the treatment of intraperitoneal abscesses. The treatment was successful in 95% while 5% of the patients in both groups died from progressive septic shock; one complication in each group occurred. There is a significant difference in terms of hospital stay (18 vs. 26 days) that favor the percutaneous treatment. PMID- 8474305 TI - [How frequent is the diagnosis of GI metastasis in an endoscopic patient sample in general internal medicine clinics> Results of a questionnaire survey of 34 medical clinics]. AB - With the aim of analysing the frequency of gastrointestinal (GI) metastases identified by endoscopic procedures, a survey was conducted by questionnaire, which was completed by 34 of 127 medical departments. Peritoneal carcinosis and direct tumor extension were disregarded. One GI metastasis (duodenum) was verified among 3477 upper GI tract endoscopies. Primary site was cutaneous melanoma. In another case metastatic origin is discussed (esophagus). Considering the average frequency of 102 upper GI tract endoscopies performed by the collaborating centers, one case of gastroduodenal metastasis could be expected every 17 (34) months in these institutions. 1634 examinations of the colon and rectum did not reveal any metastatic tumor growth. A longterm study is planned to provide further statistically reliable prevalence data. PMID- 8474306 TI - [Spontaneous rupture of an umbilical hernia in decompensated liver cirrhosis]. AB - The case of a spontaneous rupture of an umbilical hernia of a 52 year old patient, secondary to cirrhosis of the liver, is described as a rare complication of portal hypertension with massive ascites. Additionally a survey of the literature is given. PMID- 8474307 TI - [Cerebral vasculitis in Crohn disease]. AB - Central nervous system vasculitis in Crohn's disease. A 36-years old man was referred to the hospital because of severe headache, vertigo and right sided combined motor-sensory hemiparesis. There was a history of Crohn's disease with an acute exacerbation only two months ago. Magnetic resonance imaging detected a vascular lesion of the left brainstem and serologic investigations revealed circulating immunocomplexes and p-antineutrophil cytoplasmic autoantibodies (p ANCA). Further investigations care no evidence of arteriosclerotic cerebrovascular disease. These findings therefore suggest that cerebral vasculitis secondary to Crohn's disease was the underlying cause of this focal neurologic deficit. PMID- 8474308 TI - Hypolipidemic effects of nicotinic acid in patients with familial defective apolipoprotein B-100. AB - Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which an amino acid substitution in apolipoprotein B-100 results in low-density lipoprotein (LDL) particles that bind poorly to the LDL receptor and accumulate in plasma. Patients with FDB described to date have been heterozygous for this disorder, and their plasma contains both normal and defective-binding LDL particles. We have evaluated the hypocholesterolemic effects of nicotinic acid (3 g/d) in four patients with FDB, and compared the response to that of nine patients with heterozygous familial hypercholesterolemia (FH). Concentrations of LDL decreased by 24% in patients with FDB and by 14% in patients with FH. These results support the view that drugs which reduce LDL synthesis may be particularly effective in the treatment of patients with FDB. PMID- 8474309 TI - Age-related changes in hepatic and splenic insulin receptors and serum insulin and glucose levels in inbred mice. AB - Inbred mice of strains A/J, DBA/1J, and SJL/J were housed and aged in our animal colony, and parameters of carbohydrate metabolism were assessed at various ages. The patterns of age-related change were both organ- and strain-specific. Age related changes in two of the strains were associated with relative carbohydrate intolerance. Common to all three strains was a biphasic pattern of change in hepatic insulin receptor number, with a decrease in early life and a return to earlier levels late in life. In both A/J and DBA/1J mice, there was a sharp increase in serum insulin level (twofold to 9.7-fold) that corresponded to the decrease in hepatic insulin receptors and was associated with hyperglycemia; no significant change in serum insulin or glucose levels was seen in SJL/J mice, despite a similar biphasic pattern in hepatic insulin receptor concentration. Age related changes in splenic insulin receptors resembled changes in the liver in A/J and SJL/J mice, ie, there were synchronous biphasic age-related patterns. This was not the case in the spleens of DBA/1J mice, in which we did not observe age-related changes. There was no change in insulin receptor affinity with age, nor was there any difference in affinity between tissues or mouse strains. The pattern of change in hepatic insulin receptors and serum insulin levels was more complex than has been previously recognized. We do not know the mechanisms responsible for this complex pattern, but it must involve at least two discrete age-related events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474310 TI - Comparison of the continuously calculated fractional splanchnic extraction of insulin with its fractional disappearance using a new double-tracer technique. AB - These studies were designed to calculate the fractional disappearance rate (FDR) and splanchnic extraction of insulin in response to an exogenous (intraperitoneal) input of insulin. A double-tracer technique using insulin tritiated on both the A1 and B1 positions was introduced for the measurement of hepatic extraction. The A1 tracer, not previously characterized in vivo, was compared in terms of its kinetics with H3-B1-insulin and unlabeled insulin. The metabolic clearance rates (MCR) of the three insulins were identical, as were the decay curves of the two tracers. To measure splanchnic insulin extraction, one tracer was infused systemically to evaluate the FDR of insulin, and the second was infused into the splanchnic circulation (superior mesenteric artery) and its peripheral appearance was calculated. Splanchnic extraction was determined from the difference between this rate of appearance and the rate of infusion of the mesenteric tracer. After intraperitoneal insulin injection, insulin levels increased to peaks of 549 +/- 93 microU/mL (portal vein) and 473 +/- 99 microU/mL (inferior vena cava) and decreased to basal levels over 3 hours. The FDR decreased from 0.295 +/- 0.051 min-1 to 0.125 +/- 0.026 min-1, and splanchnic extraction decreased from 0.534 +/- 0.06 to 0.232 +/- 0.088. The latter returned to near-basal values more rapidly than did the FDR. In conclusion, the kinetics of insulin both in and out of the steady state have been shown to be nonlinear through physiological insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474311 TI - The effects of lactate loading on alanine and glucose metabolism in the conscious dog. AB - The effect of lactate per se on alanine and glucose metabolism was studied in five overnight-fasted conscious dogs. Somatostatin was infused to inhibit endogenous pancreatic insulin and glucagon release and the hormones were replaced intraportally at basal rates. Saline (n = 5) or lactate (at 25 and 50 mumol.kg 1.min-1 for 90 minutes each) was infused, and blood samples were taken during the last 30 minutes of each 90-minute period. Insulin, epinephrine, norepinephrine, and cortisol levels remained unchanged during saline or lactate infusion. Glucagon level decreased slightly during lactate (94 +/- 7 to 74 +/- 9 and 79 +/- 8 pg/mL) and saline (91 +/- 8 to 90 +/- 4 and 81 +/- 11 pg/mL) infusions. There were no significant changes in lactate or alanine levels or net hepatic balances with saline infusion. Blood lactate level increased from 657 +/- 74 to 1,718 +/- 126 and 3,300 +/- 321 mumol/L (both P < .05) during the low- and high-lactate infusion periods, respectively. The liver produced lactate during the control (5.57 +/- 2.92 mumol.kg-1 x min-1) and low-lactate infusion (1.75 +/- 2.58 mumol.kg-1 x min-1) periods, but consumed lactate (3.89 +/- 3.31 mumol.kg-1 x min -1; P < .05) during the high-lactate infusion period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474312 TI - Catabolism of low-density lipoprotein is altered in experimental chronic renal failure. AB - Catabolism of low-density lipoprotein is altered in experimental chronic renal failure. In patients with chronic renal failure, cardiovascular disease accounts for a significant proportion of all deaths. Several factors contribute to the "accelerated" atherosclerosis in this population, including hyperlipidemia, the pathogenesis of which is multifactorial. We investigated low-density lipoprotein (LDL) metabolism in a remnant model of chronic renal failure in the guinea pig. After one and two-thirds nephrectomy, creatinine clearance decreased to one-sixth normal. Plasma cholesterol and triglyceride (TG) levels increased with induction of renal failure. Analysis of lipoprotein composition disclosed significant TG enrichment of both uremic very-low-density lipoprotein (VLDL) and uremic LDL compared with control lipoproteins. Plasma clearance of homologous LDL was evaluated in turnover studies in control and uremic guinea pigs. To discriminate between differences in catabolism related to the uremic lipoprotein particle and to the uremic host milieu, a crossover protocol was used comparing the fractional catabolic rate (FCR) after simultaneous injection into control and uremic animals of 125I-control LDL and 131I-uremic LDL. The FCR of native LDL was slower in uremic animals than in controls. In addition, FCR of uremic LDL was significantly less than that of control LDL in both groups. Degradation studies in cultured fibroblasts indicated substantially reduced degradation of uremic LDL compared with control LDL. These results suggest dual abnormalities of LDL catabolism in renal failure that are not only related to alterations in clearance mechanisms in the uremic environment, but also suggest important functional differences in the LDL particle itself isolated from uremic animals. PMID- 8474313 TI - Coexistence of increased levels of adiposity, insulin, and blood pressure in a young adult cohort with elevated very-low-density lipoprotein cholesterol: the Bogalusa Heart Study. AB - Clustering and interrelationships of elevated levels (> 75th percentile) of adiposity, insulin, blood pressure, and very-low-density lipoprotein cholesterol (VLDL-C) were examined in a selected subset (n = 89) of a young adult cohort aged 18 to 26 years, whose childhood (ages 10 to 18 years) VLDL-C and/or low-density lipoprotein cholesterol (LDL-C) levels were in the upper or lower percentiles of the distribution. Among the young adults with elevated VLDL-C and LDL-C levels, 23% had increased adiposity and systolic blood pressure, 17% had increased insulin levels and systolic blood pressure, 17% had increased insulin levels and adiposity, and 13% had increased insulin levels, adiposity, and systolic blood pressure; corresponding values among those with elevated VLDL-C and normal (< 75th percentile) LDL-C levels were 29%, 18%, 24%, and 18%. As adults, the group with elevated VLDL-C and LDL-C levels had increased adiposity (P = .02) and systolic blood pressure (P = .002) in comparison to those with normal VLDL-C and LDL-C levels, whereas the group with elevated VLDL-C and normal LDL-C levels had increased fasting plasma insulin levels (P = .05) and systolic blood pressure (P = .007). These 89 individuals had undergone a glucose tolerance test during childhood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474314 TI - Aerobic versus strength training for risk factor intervention in middle-aged men at high risk for coronary heart disease. AB - To compare the effects of strength training (ST) to those of aerobic training (AT) for coronary heart disease (CHD) risk factor intervention, we studied 37 previously untrained males (aged 50 +/- 9 years, mean +/- SD) before and after 20 weeks of either ST (N = 14), AT (walk/jog, N = 13), or no exercise (inactive controls, N = 10). Lipoprotein and lipid profiles, blood pressure, and glucose and insulin responses to an oral glucose tolerance test (OGTT) were assessed before and after the training period in all three groups. The ST program produced significant reductions in plasma glucose levels at 60, 90, and 120 minutes (P < .05) after glucose ingestion, whereas the AT program resulted in significant reductions only at 90 and 120 minutes (P < .05). ST also decreased insulin levels during fasting (P < .05) and at 90 and 120 minutes (P < .01) after glucose ingestion. AT decreased insulin levels at 90 and 120 minutes (P < .01) after glucose ingestion. Both training programs reduced the total area under the glucose tolerance curve for glucose (both P < .05) and insulin (both P < .05), but there were no significant differences in these changes between the two groups. None of the glucose or insulin values were significantly altered in the control group. There were no significant changes in lipoprotein and lipid profiles or blood pressure in any of the three groups. These results suggest that ST and AT have comparable effects on risk factors for CHD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474315 TI - Growth hormone treatment after abdominal surgery decreased carbohydrate oxidation and increased fat oxidation in patients with total parenteral nutrition. AB - Patients undergoing elective abdominal surgery were double-blindly randomized for treatment with growth hormone (GH) 24 IU (n = 9) or placebo (n = 10) the first 5 postoperative days while receiving total parenteral nutrition (nitrogen, 5.7 +/- .1 g/m2; energy, 1,018 +/- 12 kcal/m2, ie, 125% +/- .7% of basal metabolic rate [BMR]). Carbohydrate and fat metabolism were evaluated from indirect calorimetry, daily blood samples, and forearm substrate-flux studies. Hormone levels in plasma or blood were also determined. GH decreased carbohydrate oxidation, increased fat oxidation, and increased resting energy expenditure (REE). Free fatty acids (FFA), glycerol, and beta-hydroxybutyrate (beta-OH-B) levels increased in both arterial and venous plasma, and forearm release of FFA and glycerol increased. GH, insulin-like growth factor 1 (IGF-1), and glucagon levels in venous blood were also increased in GH-treated patients. Thus, GH induced mobilization and utilization of fat, and fat was preferred to glucose for energy requirements in patients after abdominal surgery with nutritional support. PMID- 8474316 TI - Exercise tolerance is lower in type I diabetics compared with normal young men. AB - The present investigation was conducted to study metabolic and hormonal responses to prolonged exercise to exhaustion in insulin-dependent diabetic subjects. Sixteen healthy subjects (control) and 15 diabetics with no-insulin administration for 12 hours were studied. They were submitted to short-term exercise to exhaustion on a cycle ergometer at 55% to 60% of maximum oxygen consumption (VO2max). Exercise tolerance was significantly lower in diabetic subjects (66 +/- 6.7 v 117 +/- 9.4 minutes), and glucose concentration was significantly higher in these subjects. At exhaustion, only diabetic subjects showed a significant decrease in glycemia (142 +/- 20 v 111 +/- 16 mg/dL). Lactate concentration increased significantly during exercise up to 30 minutes, but at exhaustion only control subjects showed a reduction. No significant difference in free fatty acid (FFA) concentrations was observed between the groups during a 30-minute exercise period; however, at exhaustion levels were significantly higher in control subjects. Prolactin and C-peptide concentrations were significantly lower in diabetic subjects, whereas glucagon concentration was higher. No significant differences between the groups were observed for cortisol and growth hormone (GH) concentrations. We conclude that (1) diabetic subjects show reduced exercise tolerance when no insulin is administered for 12 hours, and (2) exercise to exhaustion reduces serum glucose concentrations in insulin dependent diabetics. PMID- 8474317 TI - In vivo administration of interleukin-1 alpha induces muscle proteolysis in normal and adrenalectomized rats. AB - The effect on muscle protein turnover of recombinant interleukin-1 alpha (rIL-1 alpha), 300 micrograms/kg body weight (BW) administered intraperitoneally (IP) in three divided doses over 18 hours, was studied in rats. Protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein, and total and myofibrillar protein breakdown rates were determined by measuring release of tyrosine and 3-methylhistidine, respectively, in incubated extensor digitorum longus muscles. To assess the role of glucocorticoids in rIL-1 alpha related metabolic alterations, plasma levels of corticosterone following rIL-1 alpha injection and the effect of rIL-1 alpha on muscle protein breakdown in adrenalectomized and sham-adrenalectomized rats were determined. Total and myofibrillar protein breakdown rates were increased by 45% and 167%, respectively, following treatment of normal rats with rIL-1 alpha; muscle protein synthesis was not altered by the cytokine. Plasma corticosterone levels were markedly elevated following rIL-1 alpha injection, with a maximal level occurring at 30 minutes. However, administration of rIL-1 alpha resulted in increased total and myofibrillar protein breakdown rates in both adrenalectomized and sham adrenalectomized rats. The results suggest that increased muscle proteolysis following administration of rIL-1 alpha is independent of glucocorticoids. PMID- 8474318 TI - Dose-dependency of the glycemic response to starch-rich meals in non-insulin dependent diabetic subjects: studies with varying amounts of white rice. AB - The study objective was to determine the dose-response relationships between postprandial blood glucose, insulin, and glucagon responses and the amount of starch ingested in non-insulin-dependent diabetic (NIDDM) subjects. Three test meals were served in random order with a 7-day interval. Mixed meals of 23, 46, and 69 g (raw weight) parboiled white rice containing approximately 20, 40, and 60 g available carbohydrate were served cooked with 167 g meat sauce on 3 separate days. Patients ingested the meals after a 12-hour fast. Clear-cut dose response relationships between the amount of starch ingested and postprandial peak blood glucose values (R = .99), glucose response areas (R = .99), and insulin response areas (R = .98) were found. Glucose response areas to meals of 20, 40, and 60 g carbohydrate as white rice differed significantly (P < .05) at 139 +/- 58, 285 +/- 86, and 453 +/- 113 mmol/L x 280 min, respectively. Insulin response areas to meals of 23 g rice (11.382 +/- 2,220 pmol/L x 240 min) were significantly lower compared with response areas to 46 g rice (18.138 +/- 3,522 pmol/L x 240 min) and 69 g rice (21.312 +/- 2,970 pmol/L x 240 min), with the latter two values being similar. Glucagon response areas showed an inverse pattern to glucose response areas, reaching 3,450 +/- 823, 2,715 +/- 651, and 2,168 +/- 553 pmol/L x 240 min, but differences did not reach statistical significance. PMID- 8474319 TI - Beneficial effects of acarbose in the atherosclerosis-prone JCR:LA-corpulent rat. AB - The JCR:LA-corpulent rat is a strain exhibiting marked obesity and metabolic derangements characterized by hyperlipidemia due to hypersecretion of very-low density lipoprotein (VLDL) and severe insulin resistance. The corpulent male rats spontaneously develop atherosclerosis and ischemic myocardial lesions. Male corpulent rats were treated with acarbose in the presence and absence of sugar supplemented diets. The acarbose-treated rats had lower body weights at 3 months of age with unaltered food consumption, and a similar effect was seen with a high fructose diet. Fasting insulin concentrations were decreased significantly in acarbose-treated animals at both 3 and 9 months of age, and the rate of plasma glucose disappearance increased at 3 months of age. Acarbose treatment did not affect whole-serum triglyceride concentrations, but there were modest decreases in cholesterol levels. Sugar-supplemented diets caused no significant changes in insulin or glucose concentrations, and caused small increases in nonesterified cholesterol only. Fructose- but not sucrose-supplemented diets were associated with a significantly decreased frequency of old scarred myocardial lesions. The frequency of occurrence of such lesions was also decreased by acarbose treatment. This effect of acarbose treatment may reflect improvement in insulin and glucose metabolism in treated rats. The decrease in myocardial lesions in fructose-fed rats may be secondary to increased carbohydrate metabolism via the pathways leading from fructose to triglyceride. PMID- 8474320 TI - Effect of glucose, insulin, and hypertonicity on atrial natriuretic peptide levels in man. AB - To determine the effects of hyperglycemia and hyperinsulinemia on atrial natriuretic peptide (ANP) levels in man, we studied normotensive nondiabetic volunteers (aged 25 to 63 years) during infusion of insulin and/or 20% dextrose (glucose clamp technique) to achieve three different states of "glycemia/hyperinsulinemia," as follows: (1) euglycemia for 2 hours during infusion of insulin (80 mU.m-2.min-1), resulting in plasma insulin levels of approximately 1,200 pmol/L (n = 9); (2) moderate stable hyperglycemia at a level of 11 mmol/L (198 mg/dL) for 2 hours, with infusion of glucagon-like peptide-1 (7 37) amide (GLP-1) during the second hour, which increased endogenous insulin responses to approximately 2,100 pmol/L (n = 9); and (3) marked stable hyperglycemia at a level of 18.5 mmol/L (330 mg/dL) for 2 hours, with endogenous insulin responses of approximately 720 pmol/L (n = 9). In addition, six patients with non-insulin-dependent diabetes mellitus were studied with the GLP-1 protocol at a hyperglycemic level of 14.5 mmol/L (261 mg/dL). In normal subjects, plasma ANP levels increased significantly from 3.0 +/- 0.4 to 4.6 +/- 0.8 pmol/L during marked hyperglycemia, but did not change during euglycemia or moderate hyperglycemia despite higher insulin levels (P < .01, ANOVA). Sodium excretion rates were also highest during the marked hyperglycemic study (125 +/- 14 v 91 +/ 7 v 74 +/- 10 mumol/min, P < .05, marked v moderate hyperglycemia v euglycemia). In diabetic subjects, ANP levels increased significantly from 12.5 +/- 4.1 to 21.1 +/- 5.0 pmol/L during hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474321 TI - Mechanisms of high-density lipoprotein reduction after probucol treatment: changes in plasma cholesterol esterification/transfer and lipase activities. AB - Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] -32%), HDL2-C (-65%), HDL3-C (-22%), apolipoprotein (apo)A-I (-27%), and apo A-II (-11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (-7%), LPL (+4%), and HL (-7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL2-C, and apo A-I levels (r = -.63, -.52, and -.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG) enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma. PMID- 8474322 TI - Relationships between lipoprotein(a), lipids, apolipoproteins, basal and stimulated fibrinolytic regulators, and D-dimer. AB - In 191 newly referred hyperlipidemic patients, our specific aim was to assess relationships between levels of lipoprotein(a) [Lp(a)], lipids, apolipoproteins, regulators of basal and stimulated fibrinolytic activity, and D-dimer, a measure of in vivo fibrinolysis. Lp(a) levels correlated with none of the measures of basal fibrinolytic regulators or D-dimer. In 25 patients, levels of stimulated regulators of fibrinolytic activity and D-dimer were measured after 10-minute cuff venous occlusion. Lp(a) levels again correlated with none of the stimulated regulators of fibrinolytic activity or D-dimer. However, both basal and stimulated levels of fibrinolytic regulators and D-dimer were closely related to other major risk factors for coronary heart disease (CHD) including triglyceride, apolipoprotein (apo) A1, apo B, Quetelet index (QI), and sex. By stepwise regression in 191 patients, the following standardized partial regression coefficients were significant (P < or = .05), and model R2 and P values were as follows: basal tissue plasminogen activator (tPA) with apo B-.18, with time .17, with QI -.28, R2 = 17%, P < or = .0001; basal plasminogen activator inhibitor (PAI) with apo B..25, with time -.15, with QI .17, R2 = 14%, P < or = .0001; basal alpha 2-antiplasmin with apo A1.14, with apo B.24, with QI.17, with sex .30, R2 = 25%, P < .0001; basal plasminogen with A1.15, with apo B.21, with QI.17, with sex.17, R2 = 15%, P < or = .0001; basal fibrinogen with Lp(a).17, with QI.21, with sex.26, R2 = 14%, P < or = .0001; D-dimer with sex.15, R2 = 21%, P < or = .048. Given the absence of any relationship between Lp(a) levels and inhibition or stimulation of fibrinolysis regulators or D-dimer either in the basal or stimulated state, we postulate that Lp(a)'s major atherogenic effects are mediated by mechanisms other than reduction of fibrinolysis stimulation or in vivo fibrinolysis. PMID- 8474323 TI - Hypoalphalipoproteinemia: postprandial response of subjects with preprandial normotriglyceridemia and hypertriglyceridemia to various diets. AB - The effect of a single oral fat meal (60 g fat/m2 body surface area) enriched in either saturated (SFA) or polyunsaturated ([PUFA] omega-6 or omega-3) fatty acids on postprandial lipoprotein levels was studied in four men with primary hypoalphalipoproteinemia (HP) and in four age- and sex-matched controls. Vitamin A was included in the meal to label intestinally derived triglyceride-rich particles (TRP) with retinyl palmitate (RP). The HP subjects were either mildly hypertriglyceridemic (group A) or normotriglyceridemic (group B) and were phenotyped for post-heparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and apolipoprotein (apo) E isoforms. Postprandial total plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and RP and TG concentrations in the chylomicron (Sf > 1,000) and nonchylomicron (Sf > 1,000) fractions were evaluated for 24 hours after the meal. At each time point, HDL composition and size and apolipoprotein distributions were also measured. Following the SFA meal, HP subjects had maximal plasma TG levels at 8 hours (4 hours in controls) with a slow return to baseline levels at 12 to 24 hours (8 to 12 hours for controls). In contrast, after the omega-6 meal plasma TG levels decreased in group A subjects, while group B subjects and controls showed only a small increase. The results after the omega-6 meal were intermediate between the SFA and the omega-3 meal. When compared with group B, subjects in group A showed higher levels of RP-associated TRP, slower clearance rates, 30% to 50% lower fasting LPL activity, and 1.5-fold to twofold higher fasting plasma apo C-III levels. The major preprandial HDL subclass in HP subjects was HDL3, which showed a relative decrease in cholesterol esters (CE) and an increase in TG levels following the SFA meal. After the omega-3 meal, HDL of group A subjects showed a decrease in TG, a reciprocal increase in CE, and either no changes or minor changes in phospholipid (PL) and free-cholesterol (FC) levels. The results show that HP subjects with mild preprandial hypertriglyceridemia respond to a single fat meal differently than subjects with normotriglyceridemia, and that this difference is the result of HP in addition to other factors such as low LPL and HTGL activities, high plasma apo C-III levels, and apo E2 phenotype. PMID- 8474324 TI - Checklist for the methods section of dietary investigations. PMID- 8474325 TI - Ketone and lactate metabolism: an exchange of conclusions. PMID- 8474326 TI - Ketone and lactate metabolism: an exchange of conclusions. PMID- 8474327 TI - In-frame gene fusion. PMID- 8474328 TI - Gene expression in cell-free system on preparative scale. PMID- 8474329 TI - Cell-free expression vector: use of insect virus translational initiation signal for in vitro gene expression. PMID- 8474330 TI - Cell-free expression of large collections of cDNA clones using positive-selection lambda phage vectors. PMID- 8474331 TI - Site-specific mutagenesis in plasmids: a gapped circle method. PMID- 8474332 TI - Polymerase chain reaction-based point mutagenesis protocol. PMID- 8474333 TI - High-level secretion of heterologous proteins by Bacillus brevis. PMID- 8474334 TI - Gene splicing by overlap extension. PMID- 8474335 TI - Chemical cleavage of mismatch to detect mutations. PMID- 8474336 TI - Vector pPLEX for expression of nonfusion polypeptides in Escherichia coli. PMID- 8474337 TI - Expression and screening in yeast of genes mutagenized in vitro. PMID- 8474338 TI - Screening of complementary DNA library using radiolabeled antigen. PMID- 8474340 TI - Rapid colony hybridization on Whatman 541 paper using oligonucleotide probes. PMID- 8474339 TI - Alternatives to X-galactopyranoside in screening recombinant clones based on pUC derived plasmid vectors. PMID- 8474341 TI - Detection of DNA in Southern blots with chemiluminescence. AB - The chemiluminescent detection methods described in this chapter have been successfully applied to the detection of plasmid DNA and genomic DNA in Southern and sequencing protocols. The high sensitivity and the simplicity of AMPPD are instrumental in making the chemiluminescent detection of DNA successful in hybridization assays. This detection technique has also been used to detect DNA in dot blots and in situ hybridization experiments as well as proteins in enzyme linked immunosorbent assays (ELISAs) and Western blots. PMID- 8474342 TI - Picogram detection of stable dye-DNA intercalation complexes with two-color laser excited confocal fluorescence gel scanner. AB - The stable complexes between highly fluorescent, polyfunctional intercalators and dsDNA can be used to detect dsDNA in agarose gels at picogram levels and for multicolor detection of multiplexed dsDNA fragments. Development of additional DNA-binding fluorophores with appropriate spectroscopic properties will expand the range of applications. In principle, the DNA-dye intercalation complexes represent a more sensitive alternative to an established approach to fluorescent labeling and detection of restriction fragments by ligation to single-stranded short oligonucleotides labeled with different fluorochromes, followed by separation on denaturing polyacrylamide gels. The latter technique gives near single-base resolution up to 400 bases and the ability to quantitate fragment size up to 2000 bases, and has been successfully applied to cosmid mapping. Detection of DNA fragments as intercalation complexes requires that the separations be performed on agarose gels under nondenaturing conditions. Such conditions have been used for extensive mapping of yeast cosmids with postelectrophoresis staining with ethidium bromide. For the patterns on agarose gels, the magnitude of the "error window," which specifies how similar two fragments must be before the corresponding fragments in different digests are paired, was reported to be strongly size dependent. The error window was expanded by a factor of 1.3 for fragments from 400 to 600 bp, 1.2 for fragments from 600 to 800 bp, and 1.1 for fragments from 800 to 1000 bp. Moreover, it was necessary to introduce corrections for systematic differences between size estimates taken from two different gels. For the multiplexing procedure described here, the size estimates for fragments from 600 bp to over 23 kbp were in close agreement with actual sizes as determined from DNA sequence (Table I), and certainly within the error windows given above. The multiplexing procedure should also minimize errors introduced by gel-to-gel variations in mobility, because the standard and unknowns are always run in the same lanes. Kohara et al. established a physical map of almost the entire Escherichia coli chromosome by analysis of a large genomic library. In this case, partial restriction digests were used to generate patterns of fragments and the mapping was performed by agarose gel electrophoresis. The disadvantage of this approach is that fewer fragments are generated. However, this is compensated for by the fact that partial digests reveal the order of the fragments produced and thus greatly increase the amount of information relevant to the question of overlap between different DNA fragments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8474343 TI - Alginate as matrix support for yeast artificial chromosome cloning. PMID- 8474344 TI - Genome walking by single specific primer-polymerase chain reaction. PMID- 8474345 TI - Application of electroporation in recombinant DNA technology. PMID- 8474346 TI - Stable high-level gene expression in mammalian cells by T7 phage RNA polymerase. PMID- 8474347 TI - Transformation of intact yeast cells by electroporation. PMID- 8474348 TI - Optimizing the biolistic process for different biological applications. AB - The biolistic process is still rapidly evolving. We do not anticipate further major improvements in biolistic apparatus. There will probably still be further major improvements in particles, DNA coating, and vectors, as well as significant further advances in understanding of biological determinants of cell penetration and survival. The technology has currently reached the point at which it can be readily and reliably used for a wide range of applications. Given the information presented in this chapter, new applications can be optimized fairly readily. PMID- 8474349 TI - Chloroplast transformation in Chlamydomonas. PMID- 8474350 TI - Foreign gene expression in chloroplasts of higher plants mediated by tungsten particle bombardment. PMID- 8474351 TI - Generation and analysis of vaccinia virus recombinants. PMID- 8474352 TI - Gene transfer into primary and established mammalian cell lines with lipopolyamine-coated DNA. PMID- 8474354 TI - Molecular basis of cancer: oncogenes and tumor suppressor genes. PMID- 8474353 TI - Overproduction of proteins using expression-cassette polymerase chain reaction. PMID- 8474355 TI - Efficient adsorption of lysostaphin on bacterial cells of lysostaphin-resistant Staphylococcus aureus mutant. AB - A simple and efficient method for the purification of staphylolytic endopeptidase (lysostaphin) contained in culture supernatant of Staphylococcus simulans biovar staphylolyticus strain by adsorption of the enzyme on bacterial cells of lysostaphin-resistant S. aureus mutant was successfully devised. Lysostaphin was sufficiently absorbed on the heat-killed mutant cells derived from S. aureus Cowan I and efficiently eluted by 3 M KSCN. Enzyme preparation obtained by a single procedure of the affinity purification was pure enough for practical use. The yield of the enzyme was 25 mg from 1 liter culture and recovery rate was 64%. PMID- 8474356 TI - Applications of polymerase chain reaction for identification of dengue viruses isolated from patient sera. AB - A simple and sensitive procedure of reverse transcriptase polymerase chain reaction (RT-PCR) was developed previously such that all 4 serotypes of dengue viruses could be detected and their serotypes identified simultaneously in a single-step procedure. In this study we compared the RT-PCR with a conventional immunoperoxidase (PAP) staining method for the identification of dengue viruses currently isolated from patient sera. Sixty-six sera taken from dengue hemorrhagic fever (DHF) patients were subjected to virus isolation by inoculating onto C6/36 cell cultures. Screening for the presence of dengue viruses in culture fluids was done after 7 days of incubation by PAP staining using hyperimmune rabbit anti-dengue virus antibody as the primary reagent. Dengue viruses in positive cultures were further identified for their serotypes by PAP using type specific monoclonal antibodies (MAb) and by RT-PCR. Thirty-two out of the 66 serum specimens tested (48.5%) were positive for dengue viruses. Of these, 5 were type 1 (DEN-1), 25 were type 2 (DEN-2) and 2 contained both DEN-1 and DEN-2. All cultures that were positive by PAP method were also positive by RT-PCR and vice versa. Thus, the results obtained by RT-PCR were in good agreement with those by PAP. It is important to point out that while all 5 DEN-1 isolates reacted readily with the MAb 1F1, only 2 of them could be identified by the MAb 15F3. Our data suggest that antigenic variation among DEN-1 isolates occur frequently and this should be taken into consideration in the selection of appropriate type-specific MAb for serotyping of dengue viruses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474357 TI - Suppression of ADCC by immune complexes formed in vitro in Mycobacterium leprae infected mice. AB - Antibody-dependent cellular cytotoxicity (ADCC) was assessed in mice infected experimentally with Mycobacterium leprae and injected simultaneously with in vitro-formed immune complexes (IC). Significant decrease in the ADCC function was observed in animals given IC at zero day (0dIC) and 3 months (3mIC) post inoculation with M. leprae, when ADCC activity was assessed at 3, 6 and 9 months period. From the data obtained we believe that ADCC is suppressed by IC formed in vitro. PMID- 8474358 TI - Cholera toxin (choleragen)-polymorphonuclear leukocyte interactions: effect on migration in vitro and Fc gamma R-dependent phagocytic and bactericidal activity. AB - PMNL leukocytosis is a feature common to many types of infectious and inflammatory diseases. How PMNL are recruited to tissues is not yet clear although it is a question that has considerable clinical importance. We investigated the function of PMNL which migrated through an artificial barrier (Chinese hamster ovary (CHO) cells, collagen and nylon cloth membrane) subjected to CT or choleragenoid treatment toward plain medium (the same RPMI in the upper and lower chamber) or medium containing chemotactic factor (fMLP or LPS or ZAS). CT treatment significantly (P < 0.01) reduced the Fc gamma R expression on the surface of PMNL. The PMNL functions, namely, migration, phagocytic activity and intracellular killing of staphylococci, also have been reduced significantly (P < 0.01). Fc gamma R expression and some functions of PMNL that migrate to chemoattractants were reduced, irrespective of the presence or absence of CT; however, the inhibitory effect of CT on PMNL function was observed only when PMNL migrate to the lower chamber without chemotactic factor. On the other hand choleragenoid treatment of CHO cells did not have any significant influence on PMNL function and Fc gamma R expression. In conclusion, our experiments demonstrate that CT reduces EAFc rosetting and the Fc gamma R-dependent phagocytic and bactericidal activity of bovine blood PMNL. PMID- 8474359 TI - Inhibitory effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) on germination of Bacillus cereus T spores. AB - Effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB 8), a calcium antagonist, on germination of Bacillus cereus T spores induced by L alanine and inosine was investigated. TMB-8 had no effect on the germination of heat-activated spores, whereas it inhibited that of nonactivated spores. The TMB 8 inhibitory effect was antagonized competitively by inosine, but not by L alanine. Addition of Ca2+ reversed the inhibitory effect of TMB-8 in a dose related fashion. Based on the results, a role of inosine and a site(s) for inhibitory action of TMB-8 in the process leading to the germination of nonactivated spores were discussed. PMID- 8474360 TI - Effects of cytochalasins B and D on Staphylococcus aureus adherence to and ingestion by mouse renal cells from primary culture. AB - Cytochalasin B (CB) and cytochalasin D (CD), inhibitors of microfilament function of host cell, were examined for their effects on Staphylococcus aureus Cowan I adherence to and ingestion by several types of the hyperosmolarity-tolerant (HOT) cells obtained from primary culture of mouse kidney. Staphylococcal adherence to the HOT cells with epithelial appearance was extraordinarily enhanced by the treatment of those cells with both 5 micrograms/ml of CB and CD. In particular, staphylococci adhered to the periphery rather than the center of each cytochalasin-treated cell. Staphylococcal ingestion by all types of the HOT cells was markedly inhibited by CD in spite of the enhanced adherence. Contrary to our expectation, inhibition by CB was incomplete, and the enhanced adherence of staphylococci to CB-treated cells resulted in the enhanced ingestion. PMID- 8474361 TI - Fibronectin-binding proteins of a human oral spirochete Treponema denticola. AB - Major polypeptides from a human oral spirochete Treponema denticola ATCC 33520 were examined to demonstrate their ability to bind to human plasma fibronectin by immunoblot analysis. Of three main polypeptides separated on sodium dodecyl sulfate polyacrylamide gels 53,000-daltons (53-kDa) and 72-kDa surface antigenic proteins and a 38-kDa axial flagellar protein showed the ability to bind to fibronectin, suggesting that fibronectin on host cells can mediate cytoadherence of T. denticola by its binding to the surface proteins or the exposed 38-kDa axial flagellar protein. PMID- 8474362 TI - Protective activity of antisera against isolates of Borrelia burgdorferi from various geographical origins. AB - Antisera from rabbits immunized with two Japanese strains of Borrelia burgdorferi, HP3 an isolate from Ixodes persulcatus and HO14 an isolate from I. ovatus, or the European strain P/Bi isolated from human cerebrospinal fluid (CSF) did not passively protect hamsters from challenge with the infectious strain 297, a North American isolate from patient CSF. Antisera to strains 297 and B31, a North American isolate from I. dammini, however, provided protective effect to challenge with strain 297. Immune mice sera in the presence of homologous B. burgdorferi antigen induced the production of oxygen intermediates from mouse peritoneal exudate cells. Heterologous B. burgdorferi antigen had no effect. These results suggest that antigenic properties of Japanese strains are different from those of North American and European isolates. PMID- 8474363 TI - Genetic transformation in Helicobacter pylori. AB - Genetic transformation in Helicobacter pylori was investigated by using its chromosomal and plasmid DNAs. Six out of the eight strains exhibited the natural competence for incorporation of H. pylori chromosomal DNA, and all the strains incorporated the donor DNA efficiently by washing and concentrating the cells with a glycerol solution. The much higher frequency of transformation was obtained in each strain by means of electroporation. Electroporation experiments were also conducted by use of the recombinant DNAs consisting of the H. pylori and Escherichia coli plasmids as the donors, and the occurrence of the homologous recombination was demonstrated between the incoming H. pylori plasmid-derived region and the corresponding region of the originally residing plasmid in H. pylori. PMID- 8474364 TI - Quality assurance of hospital transfusion practice. PMID- 8474365 TI - Monash University Centre for Rural Health. PMID- 8474366 TI - The International Association of Bioethics. PMID- 8474367 TI - Child homicide--the extreme of child abuse. AB - OBJECTIVE: To review cases of fatal child abuse, looking for any characteristic features of these cases. DESIGN AND SETTING: A case review of all childhood deaths at The Children's Hospital, Camperdown, between January 1976 and December 1990. Cases with a definite diagnosis of child abuse were extracted. Cases where there was only a suspicion of child abuse as the cause of death were not included. SUBJECTS: Seventeen cases of fatal child abuse were reviewed with emphasis on autopsy findings and sociological data. RESULTS: All children who died were less than three years of age; nine were under one year. Seventy-six per cent died from head injury and 24% from asphyxia or strangulation. In addition to their fatal injuries, 41% had multiple bruises on the trunk and limbs. Thirty five per cent had evidence of previous physical abuse. CONCLUSIONS: The commonest age for fatal child abuse is the first year of life. When physical abuse occurs in children under three years, and particularly under one year, a thorough assessment, follow-up and institution of appropriate supportive services are essential, as the abuse may be an early warning of a subsequent fatal episode of abuse. The introduction of a process of review of child deaths may increase awareness of and help prevent fatal child abuse. PMID- 8474368 TI - Preoperative autologous blood donation. Linkage of the public and private hospital sectors. AB - OBJECTIVE: To evaluate the safety and efficacy of a preoperative autologous blood donation (PABD) program with liberal patient exclusion criteria. DESIGN: Prospective patient accrual from September 1990 to May 1992. SETTING: A PABD program in a public tertiary care hospital linked with a specialist orthopaedic practice in a private hospital. PATIENTS: One hundred and twenty patients consecutively scheduled for orthopaedic surgery were referred for PABD. There were 77 women (median age, 63 years) and 43 men (median age, 62 years). One-third of patients were 70 or more years old. Coexistent medical disease, mainly cardiovascular, was present in 46% of patients and 3% were excluded because of coexisting morbidity. Total hip or total knee replacement was performed in a private hospital with intraoperative or postoperative blood salvage in 37% of the patients. OUTCOME MEASURES: Adverse effects of PABD, autologous blood collected and used and homologous blood transfused. RESULTS: One hundred and sixteen patients donated 267 units of autologous blood. In 70 patients undergoing total hip replacement, 78% donated three and 20% donated two units, with 95% of autologous blood being used. In 38 patients undergoing total knee replacement, 42% donated two units and 55% donated one unit, with 87% of autologous blood being transfused. Seventy-eight per cent of all patients only received autologous blood. In the remaining patients, homologous blood use was confined to two units or less in 80%. Hypotensive episodes associated with phlebotomy occurred in 3% of patients, and 13% of patients had preoperative haemoglobin levels ranging from 85 100 g/L without adverse clinical effects. CONCLUSION: A hospital-based PABD program with less strict patient exclusion criteria does not prejudice the clinical status of the donors. Its linkage to private hospitals can significantly reduce the use of homologous blood in selected elective surgery. PMID- 8474369 TI - Improving general practitioner involvement in urban hospitals. Departments or divisions of general practice. AB - OBJECTIVE: To discover what measures have been taken in urban Australian hospitals to involve general practitioners (GPs) in public hospital services. DESIGN: A descriptive study. Data were collected by postal survey. SETTING: Hospitals in urban areas. MAIN OUTCOME MEASURES: Appointment of GP affiliates or associates, existence of departments or divisions of general practice, appointed GP liaison positions and formal arrangements for GP shared care and discharge planning. RESULTS: Ninety-five of 102 hospitals (93%) responded to a postal survey. Sixty-five per cent of respondent hospitals had appointed GP affiliates or associates, 32% had a division or department of general practice and 41% had a designated GP liaison position. Forty per cent had formal GP shared care programs and 14% had formal GP involvement in discharge planning. CONCLUSION: There was a high level of adoption of measures to involve GPs in urban hospitals. However, only a minority of hospitals had comprehensive measures in place and sufficient support for this to occur. PMID- 8474370 TI - Assessment and selection of patients for day surgery in a public hospital. AB - OBJECTIVE: To describe methods used for adult patient assessment and selection for day case surgery at a major Australian teaching hospital. DESIGN: A prospective analysis of assessment data and information from the unit's computerised database. PATIENTS AND SETTING: Five thousand day patients consecutively admitted to the Day Surgical Unit, Royal Adelaide Hospital. MAIN OUTCOME MEASURES: The proportion of patients assessed only by trained nursing assessment staff was determined and compared with that for patients requiring additional anaesthetic assessment before surgery. The percentage of patients requiring preoperative investigations was established. Unanticipated hospital admission rates were calculated for surgical, anaesthesia-related and social reasons. RESULTS: After initial screening by a trained assessment nurse, 46% of patients required additional review by an anaesthetist before the day of surgery. The remaining 54% were assessed by an anaesthetist on the day of surgery. Preoperative investigations were ordered by anaesthetists in 8.5% of all day patients. The assessment methods outlined resulted in a 1.28% rate of unanticipated hospital admissions. This admission rate was mostly caused by complications of surgery (0.94%). Only 0.12% of patients were admitted for anaesthesia-related reasons and 0.14% were admitted for social reasons. CONCLUSIONS: This cost-effective system allows suitable patients and procedures to be identified, with a satisfactory unanticipated hospital admission rate. Satisfactory assessment also results in short preoperative waiting periods, fewer cancellations, reduced postoperative problems and more satisfied patients. The development of an efficient assessment system is aided by the use of a dedicated day surgery area with experienced nursing staff, the use of a comprehensive patient questionnaire and coordination by experienced day surgery anaesthetists. PMID- 8474371 TI - Rheumatic fever and chronic rheumatic heart disease in Yarrabah aboriginal community, north Queensland. Establishment of a prophylactic program. AB - OBJECTIVE: To establish a program for the prevention of rheumatic fever and rheumatic heart disease in a semi-isolated Aboriginal community in far north Queensland and to test its efficacy. DESIGN: A prevalence study of acute rheumatic fever and chronic rheumatic heart disease was conducted in the community in 1985 and subjects with possible acute rheumatic fever were assessed. A prophylactic antibiotic program was instituted. Records were kept of the prevalence of acute rheumatic fever for six years after the 1985 survey. A second survey of the community was held in 1991 to detect chronic rheumatic carditis resulting from undetected acute rheumatic fever. SETTING: The Yarrabah Aboriginal community in north Queensland (latitude 17 degrees S). The program was conducted by the Yarrabah Health Team, a part of the North Queensland Aboriginal Health Division. PARTICIPANTS: The whole Yarrabah community (population 1250) was invited to participate. In 1985, after the completion of an educational program, 89% of the community cooperated in the survey. There was no educational program before the 1991 survey and the compliance rate was much lower. Importantly, however, 87% of the vulnerable group (4-16 year olds) were examined. INTERVENTIONS: After the 1985 survey, all community members aged 4-16 years had throat swabs taken three times each year. Those with swabs showing Group A streptococci were treated; their contacts were also swabbed and treated if Group A streptococci were found. RESULTS: Before the institution of the swabbing program there were four new cases of acute rheumatic fever each year in the Yarrabah community. In the six years after the program was introduced only one case of acute rheumatic fever occurred. This was at a time when swabbing had temporarily lapsed for a three-month period. CONCLUSIONS: These results support the use of a prophylactic antibiotic program in Aboriginal communities as a cost effective and efficient method for the prevention of rheumatic fever. The cooperation of the community is an integral part of its success and this can be obtained by community education. PMID- 8474372 TI - A cost-utility approach to the use of 5-fluorouracil and levamisole as adjuvant chemotherapy for Dukes' C colonic carcinoma. AB - OBJECTIVE: To perform an economic evaluation of the joint use of 5-fluorouracil and levamisole as adjuvant chemotherapy in patients with fully resected Dukes' Stage C carcinoma of the colon, compared with resection and no chemotherapy. The evaluation was prompted by a study (N Engl J Med 1990; 322: 352-358) which recommended a new treatment standard for colon cancer: a 52-week course of fluorouracil, with levamisole every second week, as adjuvant chemotherapy. This recommendation raised several concerns, particularly about the quality of life of patients undergoing such a long course of chemotherapy and the costs to the health care system. METHODS: The cost of the surgery plus chemotherapy was estimated and compared with the cost of surgery alone. Descriptions of quality of life were developed from interviews with patients and health professionals, and the time trade off technique was then used to derive utility weights from a small sample (16) which were used to adjust length of life to reflect quality, in terms of a "quality adjusted life year" (QALY). RESULTS: Chemotherapy increases the total cost of treating a patient with colon cancer by $7000, from $6000 to $13,000. Incorporating quality of life reduced the extra benefit gained from the chemotherapy from 2.4 life years to 0.4 QALYs. Thus the result is a cost of $17,500 to achieve an extra QALY from this particular treatment. CONCLUSIONS: The results of this analysis are only tentative, as the quality of life descriptions were not measured over time but from a cross-sectional survey of patients, and the valuations of health states were derived from a small sample. However, we believe them to be indicative, and conclude that it is perhaps more appropriate for the use of chemotherapy to be an option rather than standard treatment until further research on these aspects is complete. PMID- 8474373 TI - It is HIV: immediate and long-term plans. PMID- 8474374 TI - The rational use of the HIV antibody test. AB - The clinical skills of the medical profession can be used to identify unsuspected HIV infection in a cost-effective way. However, other strategies are needed to optimise the detection of HIV infection and achieve the benefits to patients and the community that result from detection. PMID- 8474375 TI - Liability for failure to diagnose HIV infection and AIDS. AB - In the United States a patient has sued a doctor for failing to diagnose AIDS, resulting in a two-year delay before correct diagnosis and treatment. At least one similar case has been commenced in Australia and more are likely. The time has come when courts in this country are likely to find that failure to diagnose symptoms of HIV infection and AIDS will constitute negligence. PMID- 8474376 TI - Locum in Alice Springs. PMID- 8474377 TI - An outbreak of serotype 1 Streptococcus pneumoniae infection in central Australia. AB - An outbreak of serotype 1 Streptococcus pneumoniae infection involving both adults and children occurred in central Australia during the winter months of 1991. Eighteen patients, mainly Aboriginal men, presented with culture-positive serotype 1 bacteraemic pneumonia. In this group, 11 of 12 adults for whom medical records were available were alcohol dependent. Thirteen children who were separately studied were hospitalised with acute lower respiratory tract infection: none had bacteraemia but all had upper airway colonisation by type 1 pneumococci. Antibiotics taken by 8 of the 13 children before admission to hospital may have compromised the isolation of type 1 pneumococci from blood cultures. Since the availability of antibiotics, epidemic pneumococcal infection is infrequent and has not been reported in Australia. In three outbreaks of type 1 disease recorded elsewhere crowding and alcoholism were identified as contributory factors. In the 16 month period before this outbreak none of 162 strains of pneumococci isolated from blood (32 strains) and nasopharyngeal secretions (130 strains) from Aborigines with acute lower respiratory tract infection and meningitis in the Alice Springs region were serotype 1 organisms. PMID- 8474378 TI - Renal artery stenosis: current diagnosis and treatment. AB - OBJECTIVE: To provide an overview of the current approaches to management of renovascular disease. DATA SOURCES: A literature review was performed and key references are provided relating to diagnostic tests, particularly captopril renography and renal duplex scanning. Options for treatment are reviewed from published series to December 1991. We also draw on the experience of our own Unit. STUDY SELECTION: Data and opinions from five general reviews of renovascular disease, 10 articles on diagnostic tests and five articles relating to therapeutic approaches are summarised. CONCLUSION: There is no simple screening test for renovascular hypertension that can be applied to an unselected population of hypertensive subjects. The diagnosis depends on judicious use of non-invasive screening tests in those subjects in whom one suspects, on clinical grounds, that there may be an underlying renovascular lesion. Captopril renography and duplex scanning of renal arteries are the most reliable non invasive screening tests. A team approach with collaboration of hypertension specialist/vascular physician, vascular surgeon and experienced interventional radiologist is important for rational management and we would emphasise the importance of audit procedures. PMID- 8474379 TI - Anabolic steroid abuse and cardiac death. AB - OBJECTIVE: To examine the relationship between anabolic steroid abuse and cardiac death. We report the first two cases in Australia. They are the only reported cases in which the anabolic steroid oxymesterone has been detected. This compound has never been approved for use in Australia. CLINICAL FEATURES: Two footballers, aged 18 and 24, sustained fatal cardiac arrests while at training sessions. Both were considered fit and healthy. OUTCOME: Autopsy revealed features of a hypertrophic cardiomyopathy in the 18-year-old; the 24-year-old had findings of a myocarditis. In both cases the coronary arteries were normal and there was no evidence of coronary thrombosis. Urine in both subjects contained the anabolic steroid oxymesterone. CONCLUSIONS: There are limited clinical uses for anabolic steroids but they are widely abused by athletes in attempts to alter lean body mass and strength. Acute non-fatal myocardial infarction was first reported in 1988 and fatal myocardial infarction in 1990. While a causal relationship is hard to prove, it is possible that the anabolic steroid contributed to the increase in cardiac size in the first subject and may have increased his responsiveness to catecholamines causing an arrhythmogenic event. In the second, the inflammatory changes could have provided the focus for an arrhythmia. It would appear that anabolic steroid abuse should be considered in any athlete presenting with an acute vascular event. PMID- 8474380 TI - DNA diagnostic tests: presymptomatic and prenatal. PMID- 8474381 TI - Planning bedside teaching--2. Preparation before entering the wards. PMID- 8474382 TI - Indoor air quality and sick buildings. PMID- 8474383 TI - Laparoscopic vasectomy. PMID- 8474384 TI - Passive immunisation against hepatitis C infection. PMID- 8474385 TI - Infection and dysuria in women. PMID- 8474386 TI - Effectiveness of campaigns to increase Pap smear screening. PMID- 8474387 TI - Patterns of elder abuse. PMID- 8474388 TI - Modern methods of searching the medical literature. PMID- 8474389 TI - Modern methods of searching the medical literature. PMID- 8474390 TI - Research problems in general practice. PMID- 8474391 TI - Perineal cleansing and individual sterilised packs are not necessary for collecting midstream urine specimens. PMID- 8474392 TI - Mycoplasma hominis pneumonia. PMID- 8474393 TI - The psychoses, schizophrenia and the dementias: a continuum of liability? PMID- 8474394 TI - Pulmonary angiography in a non-teaching hospital over a 12-year period. PMID- 8474395 TI - Operative assessment and postoperative care in acutely ill patients. PMID- 8474396 TI - Haemorrhage after fine-needle aspiration biopsy of an hepatic haemangioma. PMID- 8474397 TI - Retropubic extraperitoneal endoscopy. PMID- 8474398 TI - Desflurane--a new volatile anesthetic. PMID- 8474399 TI - [Behavior of the R-amplitude in ergometric and pharmacologic stress in comparison with coronary morphologic findings in patients with coronary heart disease]. AB - The cause of R-wave amplitude changes in the ECG under load remain unknown. One of the possible aetiological factors is myocardial ischaemia. The aim of the present study was to investigate possible relationships between amplitude changes and transient myocardial ischaemia. In this retrospective study, 89 patients (74 men, 15 women) were investigated. The results of exercise ECG, a dipyridamole test and coronary angiography were available for all patients participating. The patients were divided into four groups (group I: patients with relevant coronary stenosis [n = 46], group II: patients with no relevant coronary stenoses [n = 43], group III: patients with pathological results in all three procedures [n = 29], and group IV: patients with unremarkable findings in all three investigations [n = 14] and the R-wave amplitude changes in various phases of ergometry and dipyridamole provocation were measured. All four groups showed a significance decrease in R-wave amplitude at maximum provocation as compared with baseline values. A qualitative analysis of the amplitude changes indicated a tendency for them to be dependent on the severity of coronary stenosis. A quantitative analysis, however, revealed no significant correlations between the R-wave amplitude and ST segment changes or angiographic findings. This means that R-wave changes during an exercise ECG or a dipyridamole test do not permit us to distinguish between patients with or those without coronary artery stenosis. Changes in the R-wave amplitude observed under loading must be due to factors other than myocardial ischaemia. PMID- 8474400 TI - [Can nuclear magnetic resonance tomography supplement and expand splenic diagnosis in malignant systemic diseases? Comparison of nuclear magnetic resonance tomography, ultrasound and computerized tomography findings]. AB - Can magnetic resonance imaging supplement or expand the diagnostic evaluation of the spleen in malignant systemic disease? A comparison of magnetic resonance imaging, ultrasonography and computed tomography. PMID- 8474401 TI - [Comparative study of the pharmacokinetics of amitriptyline oxide and trimipramine after single administration in healthy male probands and patients with renal failure]. AB - The pharmacokinetics of the antidepressants amitriptyline oxide and trimipramine and their major metabolites amitriptyline, nor-triptyline and desmethyltrimipramine, were studied in twelve healthy male subjects (aged from 22 to 62 years) and twelve patients (aged from 25 to 73 years) with severe renal impairment (glomerular filtration rate < 10 ml/min). Oral single doses of 60 mg amitriptyline oxide and 50 mg trimipramine, separated by a washout period, were administered to all study participants. Blood and urine samples were collected up to 120 hours after administration. For trimipramine and desmethyltrimipramine, a new HPLC method was developed. The "Fischer Somatic and Undesired Effects Check List" was used for the assessment of adverse events. The mean plasma half-life and AUC of amitriptyline oxide and its metabolites were significantly higher in patients than in healthy adults. For trimipramine the AUC was significantly higher in patients. The plasma half-life of trimipramine was longer in patients, but statistically not significant. The maximum plasma concentrations for both drugs and metabolites were at an average distinctly higher in patients. Clearance rate of amitroptylinoxide and trimipramine also differed between the two groups. Correlating with these results a high incidence and a longer persistence (in most cases > 12 hours) and more pronounced adverse effects were noted in the patient group, whereas in volunteers adverse events were only observed up to approximately eight hours. PMID- 8474402 TI - [Long-term effects of low dosage fish oil on serum lipids and lipoproteins]. AB - In a prospective and double-blind study, the long-term effects of low dose fish oil on serum lipids and lipoproteins was tested in patients with normal or moderately elevated serum lipids and compared to the effects of olive oil. The compliance to the study medication was evaluated by analysis of serum fatty acids and proved to be very good. Dietary supplementation with 9 g fish oil, respective 3.15 g n-3 fatty acids per day over one year resulted in a decrease of serum triglycerides by 26% and increase of HDL-cholesterol by 26%. Treatment with 9 g olive oil resulted in an 18% increase of HDL-cholesterol. There was no effect on serum-triglyceride levels. PMID- 8474403 TI - [Increased plasma endothelin concentrations in patients after liver transplantation and in liver cirrhosis]. AB - Endothelin, one of the most potent vasoconstrictors known today, is released by the vascular endothelium. Patients after liver transplantation and patients with liver cirrhosis show significantly higher plasma endothelin concentrations and significantly reduced results in the quantitative liver function tests (ICG-HL, GEC, Lidocaine-HL, MEGX) compared with healthy control persons. The plasma endothelin concentrations were better correlated with the more liver bloodflow dependent function tests (ICG-HL, Lidocaine-HL) than with the more metabolic capacity dependent function tests (GEC, MEGX). As cyclosporine A in vitro can increase the liberation of endothelin, we conclude that in patients after liver transplantation an endothelin mediated cyclosporine induced hepatotoxicity might be the reason for the demonstrated association. PMID- 8474404 TI - [Clinical importance of colony stimulating factors]. PMID- 8474405 TI - [3d generation cephalosporins: clinico-infectiologic evaluation after 10 years]. PMID- 8474406 TI - [Phytotherapy, an alternative?]. PMID- 8474407 TI - [Phytotherapy]. PMID- 8474408 TI - Ureaplasma urealyticum and its role in neonatal lung disease. AB - Ureaplasma urealyticum, a species of mycoplasma organisms, is a sexually transmitted organism which can cause a pneumonia in premature neonates. Ureaplasma urealyticum infection in the neonate occurs secondary to maternal transmission of the organism to the neonate. Recent studies show very low birth weight neonates with Ureaplasma urealyticum pneumonia are approximately two times more likely to develop chronic lung disease. Clinically Ureaplasma urealyticum pneumonia presents in a premature neonate and is often coexistent with hyaline membrane disease, leukopenia, thrombocytopenia, and continued respiratory distress without identification of a causative organism. Diagnosis is generally by tracheal aspirate or spinal fluid culture. Ureaplasma urealyticum requires specific culture media to grow, and recovery of the organism can take several weeks. Clinical management of the infant includes administration of erythromycin and meticulous pulmonary toilet. A case study which represents the typical presentation of Ureaplasma urealyticum pneumonia is included. PMID- 8474409 TI - Reconciliation and healing for mothers through skin-to-skin contact provided in an American tertiary level intensive care nursery. AB - Feasibility and safety of skin-to-skin contact through the Kangaroo method of care in a modern American tertiary intensive care was studied, as well as effects of this innovative care on mother's emotional reactions. Eight mother infant dyads participated in skin-to-skin contact a minimum of 4 hours each day for six days per week during a period of three consecutive weeks. The cognitive adaptation framework was used to identify themes in maternal responses. During the first week, mothers were preoccupied with childbirth events in attempts to understand their sense of loss and victimization. During the second week, maternal emotions intensified and manifested in fears for the baby's well-being and a need to discuss negative and positive emotional reactions to having a premature and sick baby. All mothers requested respite time from skin-to-skin contact, so they could deal with their emotional crises. By the third week, mothers had an increased sense of meaning, mastery, and self-esteem about what had happened to themselves and their infants. Themes of reconciliation and healing occurred when mothers placed their infant skin-to-skin in the Kangaroo position over the three consecutive weeks that this type of nursing care was experienced. PMID- 8474410 TI - Prevention of childhood diseases through vaccination. AB - Many childhood diseases can be prevented by proper immunization. The purpose of this article is to provide information about the risks and benefits associated with vaccines used in the United States for children under one year of age. Vaccines can be made from live or killed organisms and can stimulate both local and systemic immunity. The immunization schedule recommended by the American Academy of Pediatrics is presented. Information about the use of routine vaccines, their risks and the diseases they prevent, is presented. Vaccines included are diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae, influenza viruses and hepatitis B. Research is ongoing to develop new vaccines and improve those currently in use. PMID- 8474411 TI - The drug-exposed mother and infant: a regional center experience. AB - Drug-exposed mothers and infants continue to challenge maternal and infant health care resources. The woman who abuses drugs may have a complex social history and high resistance to change. Drug use may be intergenerational and long-standing. Although cocaine may be a drug of choice, there is often polydrug abuse, complicating the assessment of the newborn who may be suffering from an overall unstable intrauterine environment due to poor general health and lack of nutrition, inadequate prenatal care, and risk of exposure to contaminants from street drugs and of infection, including Hepatitis B and HIV. Infants must be thoroughly assessed and treated as any newborn at risk. Drug screening and child welfare issues are discussed. Hepatitis B immunization is recommended. Ongoing assessment of the infant and intervention techniques are described. Since many drug-exposed infants go home with their mothers, an integrated plan of care for mother and infant may contribute to a therapeutic relationship, facilitate maternal attachment behaviors, and motivate maternal rehabilitation. For nurses caring for these demanding families, burnout prevention and self-care strategies are discussed. PMID- 8474412 TI - Communicating compassion: the nursing way. PMID- 8474413 TI - Neonatal nursing in Finland. PMID- 8474414 TI - 24-hour urine collection device for low birth weight infants. PMID- 8474415 TI - Evaluation of cardiac size on the neonatal chest x-ray. AB - Cardiac size is only one parameter in the evaluation of the cardiovascular system on the neonatal chest x-ray examination. More specific information will be given in future columns when specific cardiac defects are discussed. It was our intention to present a few basic principles of x-ray interpretation before proceeding to the radiologic evaluation of specific disease states. In the next few columns we will discuss x-ray findings in infants with respiratory diseases. Hyaline membrane disease will be discussed in the next issue. PMID- 8474416 TI - Measuring the behavior of high-risk infants. PMID- 8474417 TI - Providing learning experiences for student education in the NICU. PMID- 8474418 TI - Sodium polystyrene sulfonate (Kayexalate). PMID- 8474419 TI - Chlamydia in the neonate. AB - Chlamydia trachomatis infections are the most prevalent of all sexually transmitted diseases and can be transmitted to the neonate during the birth process. Neonatal chlamydial infections include inclusion conjunctivitis and chlamydial pneumonia. These infections cause no reported mortality but are associated with a high incidence of morbidity in the newborn. Nursing care is vitally important in prevention, early detection, and management of neonates with chlamydial infections. A knowledge of Chlamydia, its risk factors, clinical manifestations, diagnosis, and treatment will assure an improved outcome for the entire neonatal population. PMID- 8474420 TI - Compendium of animal rabies control, 1993. National Association of State Public Health Veterinarians, Inc. AB - The purpose of this Compendium is to provide rabies information to veterinarians, public health officials, and others concerned with rabies control. These recommendations serve as the basis for animal rabies control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies control program. This document is reviewed annually and revised as necessary. Immunization procedure recommendations are contained in Part I; all animal rabies vaccines licensed by the United States Department of Agriculture (USDA) and marketed in the United States are listed in Part II; Part III details the principles of rabies control. PMID- 8474421 TI - Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence. PMID- 8474422 TI - Populations at risk from air pollution--United States, 1991. PMID- 8474423 TI - Nutrition and mortality assessment--southern Sudan, March 1993. AB - During the last 5 years of Sudan's decade-long civil war, increased fighting and food shortages in southern Sudan have led to displacement of large numbers of persons. In late 1992, the United Nations (UN), the government of Sudan, and factions of the Sudanese People's Liberation Army negotiated increased access for delivery of relief aid to civilians in southern Sudan. To assist in the targeting of food and other relief aid, CDC and the U.S. Agency for International Development's Office of Foreign Disaster Assistance conducted rapid assessments of nutritional status (children aged < 5 years) and mortality (persons of all ages) during March 7-19, 1993, at four sites in three states: Ame (Eastern Equatoria), Ayod and Kongor (Upper Nile), and Akon (Bahr el Ghazal) (Figure 1). This report summarizes findings of the assessments. PMID- 8474424 TI - Impact of the expanded AIDS surveillance case definition on AIDS case reporting- United States, first quarter, 1993. AB - On January 1, 1993, the acquired immunodeficiency syndrome (AIDS) surveillance case definition for adolescents and adults was expanded beyond the surveillance definition published in 1987 (1) to include all human immunodeficiency virus (HIV)-infected persons with severe immunosuppression (< 200 CD4+ T lymphocytes/microL or a CD4+ T-lymphocyte percentage of total lymphocytes of < 14), pulmonary tuberculosis (TB), recurrent pneumonia, or invasive cervical cancer. This report reviews AIDS surveillance reports CDC received from local, state, and territorial health departments during the first quarter of 1993 and summarizes the impact of the changes in the AIDS surveillance case definition. PMID- 8474425 TI - Update: dracunculiasis eradication--Nigeria, 1992. AB - The reported incidence of dracunculiasis (i.e., Guinea worm disease) in Nigeria declined substantially during 1992--the fourth consecutive year in which reports of known cases declined. This report summarizes dracunculiasis surveillance data for Nigeria and describes progress toward eradication of this disease. PMID- 8474426 TI - Linking multiple data sources in fetal alcohol syndrome surveillance--Alaska. AB - Although fetal alcohol syndrome (FAS) is a major preventable cause of mental retardation in the United States (1), surveillance for this problem is subject to at least five constraints: difficulty in identifying the syndrome at birth (2); the subjective nature of the diagnosis; variability in the severity and type of conditions associated with FAS; age-specific variations in the expression of the phenotype; and the lack of specificity in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for FAS. Previous studies have documented high rates of FAS among American Indians and Alaskan Natives (ANs) (3,4). To better ascertain cases of FAS in Alaska and to determine the prevalence of this problem among ANs, the Alaska Department of Health and Social Services (ADHSS), the Indian Health Service (IHS), and CDC linked and analyzed data from state sources (i.e., birth and death certificates and Medicaid claims), an IHS case file, and a private pediatric practice case file. This report summarizes the findings from this analysis and presents a preliminary minimum FAS prevalence rate for ANs. PMID- 8474427 TI - Surveillance for and comparison of birth defect prevalences in two geographic areas--United States, 1983-88. AB - PROBLEM/CONDITION: CDC and a number of states have developed surveillance systems to monitor the birth prevalence of major defects. REPORTING PERIOD COVERED: This report covers birth defects surveillance in Metropolitan Atlanta, Georgia and selected jurisdictions in California for the years 1983-1988. DESCRIPTION OF SYSTEM: The California Birth Defects Monitoring Program and the Metropolitan Atlanta Congenital Defects Program are two population based surveillance systems that employ similar data collection methods. The prevalence estimates for 44 diagnostic categories are based on data from 1983 to 1988 for 639,837 births in California and 152,970 births in metropolitan Atlanta. The prevalences in the two areas are compared adjusting for race, sex and maternal age using Poisson regression. RESULTS: Regional differences in the prevalence of aortic stenosis, fetal alcohol syndrome, hip dislocation/dysplasia, microcephalus, obstruction of the kidney/ureter, and scoliosis/lordosis may be attributable to general diagnostic variability. However, differences in the prevalences of arm/hand limb reduction, encephalocele, spina bifida, or trisomy 21 (Down Syndrome) are probably not attributable to differences in ascertainment because these defects are relatively easy to diagnose. INTERPRETATION: Regional differences in prenatal diagnosis and pregnancy termination may affect prevalences of trisomy 21 and spina bifida. However, the reason for differences in arm/hand limb reduction is unknown, but may be related to variability in environmental exposure, heterogeneity in gene pool, or random variation. ACTIONS TAKEN: Because of the similarities of these data bases, several collaborative studies are being implemented. In particular, the differences in the birth prevalence of spina bifida and Down Syndrome will focus attention on the impact of prenatal diagnosis. PMID- 8474428 TI - Influenza--United States, 1988-89. AB - PROBLEM/CONDITION: CDC monitors the emergence and spread of new influenza virus variants and the impact of influenza on morbidity and mortality annually from October through May. REPORTING PERIOD COVERED: This report covers United States influenza surveillance conducted from October 1988 through May 1989. DESCRIPTION OF SYSTEM: Weekly reports from the vital statistics offices of 121 cities provided an index of influenza's impact on mortality; 58 WHO collaborating laboratories reported weekly identification of influenza viruses; weekly morbidity reports were received both from the state and territorial epidemiologists and from 153 sentinel family practice physicians. Nonsystematic reports of outbreaks and unusual illnesses were received throughout the year. RESULTS: During the 1988-89 influenza season, influenza A (H1N1) and B viruses were identified in the United States with essentially equal frequency overall, although both regional and temporal patterns of predominance shifted over the course of the season. Throughout the season increases in the indices of influenza morbidity in regions where influenza B predominated. Only 7% of identified viruses were influenza A (H3N2), but not isolations of this subtype increased as the season waned and it subsequently predominated during the 1989-90 season. During the 1988-89 season outbreaks in nursing homes were reported in association with influenza B and A (H3N2), but not influenza A (H1N1). INTERPRETATION: The alternating temporal and geographic predominance of influenza strains A (H1N1) and B during the 1988-89 season emphasizes the importance of continual attention to regional viral strain surveillance, since amantadine is effective only for treatment and prophylaxis of influenza A. ACTIONS TAKEN: Weekly interim analyses of surveillance data produced throughout the season allow physicians and public health officials to make informed choices regarding appropriate use of amantadine. CDC's annual surveillance allows the observed viral variants to be assessed as candidates for inclusion as components in vaccines used in subsequent influenza seasons. PMID- 8474429 TI - Production and characterization of antibodies specific for the imidazoline receptor protein. AB - Polyclonal antibodies were raised in rabbits against a 70-kDa ligand-binding protein of the imidazoline receptor purified from solubilized bovine adrenal chromaffin cell membranes by ligand affinity chromatography. The antibodies labeled a single protein (approximately 70 kDa) in Western blots of bovine adrenal chromaffin cell membranes, inhibited 40% of specific [3H]idazoxan binding to imidazoline receptors in chromaffin cell membranes, and specifically immunoprecipitated 75% of all imidazoline-binding activity of solubilized chromaffin cell membrane proteins. The antibodies specifically immunostained heterogeneous subsets of cultured bovine chromaffin cells. They stained subpopulations of chromaffin cells of rat adrenal medulla but not the cells of adrenal cortex. We conclude that the antibodies recognize with high specificity and selectivity a approximately 70-kDa binding protein associated with or representing the imidazoline receptor that is expressed in mammalian species. Highly specific antibodies against the imidazoline receptor protein will permit mapping of the distribution of imidazoline receptors in brain and periphery and also may be useful as probes in cloning genes encoding the imidazoline receptors. PMID- 8474430 TI - Identification of residues important for ligand binding to the human 5 hydroxytryptamine1A serotonin receptor. AB - The functional significance of the conserved amino acids within transmembrane regions II and VII of the human 5-hydroxytryptamine (5-HT)1A receptor was analyzed by oligonucleotide-directed mutagenesis followed by transient expression of the mutated receptor genes in COS-1 cells. The substitution of a conserved asparagine at position 396 (transmembrane region VII) with either alanine, phenylalanine, or valine resulted in a receptor that did not bind the 5-HT1A agonist 8-hydroxy-2-(di-n-[3H]propylamino)tetralin. In contrast, replacement of Asn396 with glutamine did not affect agonist binding. In addition, serine residues at positions 391 and 393 (transmembrane domain VII) were changed to alanine. Changing the less conserved Ser391 to alanine had no effect on ligand binding. However, replacement of the conserved Ser393 with alanine reduced ligand binding by 86%. Replacement of a conserved aspartate at position 82 (transmembrane region II) with alanine also produced a receptor without detectable agonist binding. Protein immunoblotting detected receptor protein of approximately 51 kDa in both wild-type and mutant receptor-expressing cells, indicating that these mutations probably did not affect expression or processing of the protein. Importantly, the sequence of the human 5-HT1A receptor described in this paper differs from the published sequence [Nature (Lond.) 329:75-79 (1987)] in transmembrane region IV. The present sequence encodes a protein of 422 amino acids, instead of the 421-amino acid protein that has been described previously [Nature (Lond.) 329:75-79 (1987)], and has a change in the sequence in transmembrane region IV from ... RPRAL ... to ... RRAAA ..., which corresponds to the published sequence [J. Biol. Chem. 265:5825-5832 (1990)] of the rat 5-HT1A receptor. Moreover, conversion of the transmembrane region IV sequence of the present clone to that of the published sequence by site-directed mutagenesis abolished ligand binding to the receptor. PMID- 8474431 TI - Regulation of thymidylate synthase in human colon cancer cells treated with 5 fluorouracil and interferon-gamma. AB - The effects of fluorouracil (5-FU) and interferon-gamma (IFN-gamma) on the regulation of thymidylate synthase (TS) gene expression were investigated in the human colon cancer H630 cell line. By Western immunoblot analysis, TS protein levels in H630 cells were increased 3-, 5.5-, 5-, and 2.5-fold after 8-, 16-, 24 , and 36-hr exposure to 1 microM 5-FU, respectively. When H630 cells were exposed to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, increases in TS protein up to 5.5-fold were observed. A 24-hr exposure to 1 microM 5-FU resulted in a 4.5-fold increase in the level of TS protein, whereas in 5-FU/IFN-gamma treated cells TS protein was increased by only 1.8-fold, compared with control cells. IFN-gamma treatment alone did not affect TS protein levels, relative to control. Northern blot analysis revealed no changes in TS mRNA levels when H630 cells were exposed either to 1 microM 5-FU for 8-36 hr, to varying concentrations of 5-FU (0.3-10 microM) for 24 hr, or to the combination of 5-FU and IFN-gamma. Pulse-labeling studies with [35S]methionine demonstrated a 3.5-fold increase in net synthesis of TS in cells treated with 1 microM 5-FU, whereas the level of newly synthesized TS increased only 1.5-fold in cells treated with 5-FU/IFN gamma, compared with control cells. Pulse-chase studies revealed that the half lives of TS protein in control and 5-FU-treated cells were equivalent. These findings demonstrate that the increase in TS protein after 5-FU exposure and the subsequent inhibitory effect of IFN-gamma on TS protein expression are both regulated at the post-transcriptional level. PMID- 8474432 TI - [3H]PD 140376: a novel and highly selective antagonist radioligand for the cholecystokininB/gastrin receptor in guinea pig cerebral cortex and gastric mucosa. AB - The specific binding characteristics of the novel cholecystokinin (CCK)B/gastrin receptor-selective peptoid antagonist radioligand [3H]PD 140376 were investigated using membrane homogenates prepared from guinea pig cerebral cerebral cortex and gastric fundic mucosa. [3H]PD 140376 (0.01-10 nM) bound to both cerebral cortex and gastric gland homogenates with comparable high affinity (Kd, 0.1-0.2 nM) and to an apparent single population of sites with Bmax values of 119 and 296 fmol/mg of protein, respectively. The level of specific binding, defined as that displaced by unlabeled CCK sulfated octapeptide, was routinely between 60 and 70% in the cortex and between 50 and 60% in the fundic mucosa. Pharmacological characterization of the [3H]PD 140376-labeled binding sites with a series of agonist and antagonist ligands selective for each of the CCK receptor subtypes demonstrated, in both preparations, an affinity profile consistent with that of the CCKB/gastrin receptor. However, Hill slopes for the competition curves for the unlabeled agonist ligands against specific [3H]PD 140376 binding were significantly less than unity, whereas those for the antagonist ligands, including unlabeled PD 140376, were close to unity. The affinity and Hill slope for PD 140376 and the related CCKB/gastrin antagonist CI-988 were unaffected by the presence of the nonhydrolyzable GTP analogue guanylyl-5'-imidodiphosphate. In contrast, guanylyl-5'-imidodiphosphate caused a characteristic decrease in affinity and an increase in the Hill slopes towards unity for the agonist ligands CCK sulfated octapeptide and pentagastrin. The binding characteristics of unlabeled PD 140376 were also unaffected by the presence of the monovalent cation sodium. In conclusion, the present study has demonstrated that [3H]PD 140376 is the most potent and selective antagonist radioligand yet described for the characterization of CCKB/gastrin receptors in the central and peripheral nervous systems. PMID- 8474433 TI - Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. AB - The synthetic estrogen ethinylestradiol is extensively eliminated as glucuronide metabolites in humans, but the UDP-glucuronosyltransferases (UGTs) catalyzing this reaction have not been identified. Therefore, ethinylestradiol was tested as a substrate for cloned human UGTs stably expressed in V79 cell lines. Two cloned expressed human enzymes, a bilirubin UGT and a phenol UGT, were observed to catalyze the glucuronidation of ethinylestradiol. High performance liquid chromatographic analysis of the products formed revealed that the expressed bilirubin UGT specifically produced ethinylestradiol-3-glucuronide. In human liver microsomes the ratio of 3-glucuronide/17-glucuronide was 97:3. Subsequent study of the cloned expressed enzymes and human liver microsomes from Crigler Najjar patients by kinetic analysis and by substrate inhibition strongly indicated that a human liver bilirubin UGT was largely responsible for glucuronidation of ethinylestradiol. These results may provide an explanation for jaundice caused by ethinylestradiol in certain susceptible individuals. PMID- 8474434 TI - Proto-oncogene FosB: the amino terminus encodes a regulatory function required for transformation. AB - Overexpression of some members of the Fos gene family, including FosB, leads to transformation of established rodent fibroblasts. We have previously shown that transformation by FosB requires the presence of a C-terminal transcriptional activation domain. We now report that transformation by FosB also requires an intact DNA-binding domain composed of the functionally bipartite basic region and leucine zipper as well as sequences present in the N terminus that serve a regulatory function. Deletion of the N-terminal sequences results in proteins impaired in transcriptional activation and transformation. This region does not itself function as a transcriptional activation domain but instead regulates the transactivation functions present in the FosB-Jun complex. The requirement for this N-terminal region can be abolished by the presence of a strong constitutive activation domain. The primary sequence of the region that we have defined is highly conserved in the Fos family of proteins, suggesting functional conservation. PMID- 8474435 TI - In vitro definition of the yeast RNA polymerase I enhancer. AB - In vitro conditions are reported under which an EcoRI-HpaI fragment of the Saccharomyces cerevisiae ribosomal gene spacer will enhance transcription from an adjacent RNA polymerase I promoter. Enhancement is largely independent of orientation and distance and is proportional to copy number. Mapping experiments reveal that two separate regions of the EcoRI-HpaI fragment are independently capable of promoter stimulation. These regions appear to correspond to elements which have been shown by previous workers to cause enhancement in vivo. Using the detergent Sarkosyl to limit the number of rounds of transcription from each promoter, we found that the degree of enhancement is similar whether one or many rounds of transcription occur. This finding supports a model in which the enhancer increases the number of stable promoter complexes but does not alter the loading of polymerase on an active promoter. Once the stable promoter complex is formed, the enhancer can be physically severed from the promoter with no loss of enhancement. Likewise, the upstream activation region of the promoter can be severed from the core promoter domain once the stable complex has been formed. These results are interpreted to mean that the enhancer functions only to assist stable complex formation and, once that is accomplished, the enhancer is dispensable. PMID- 8474436 TI - Conservation between human and fungal squalene synthetases: similarities in structure, function, and regulation. AB - Squalene synthetase (farnesyl diphosphate:farnesyl diphosphate farnesyltransferase; EC 2.5.1.21) is thought to represent a major control point of isoprene and sterol biosynthesis in eukaryotes. We demonstrate structural and functional conservation between the enzymes from humans, a budding yeast (Saccharomyces cerevisiae), and a fission yeast (Schizosaccharomyces pombe). The amino acid sequences of the human and S. pombe proteins deduced from cloned cDNAs were compared to those of the known S. cerevisiae protein. All are predicted to encode C-terminal membrane-spanning proteins of approximately 50 kDa with similar hydropathy profiles. Extensive sequence conservation exists in regions of the enzyme proposed to interact with its prenyl substrates (i.e., two farnesyl diphosphate molecules). Many of the highly conserved regions are also present in phytoene and prephytoene diphosphate synthetases, enzymes which catalyze prenyl substrate condensation reactions analogous to that of squalene synthetase. Expression of cDNA clones encoding S. pombe or hybrid human-S. cerevisiae squalene synthetases reversed the ergosterol requirement of S. cerevisiae cells bearing ERG9 gene disruptions, showing that these enzymes can functionally replace the S. cerevisiae enzyme. Inhibition of sterol synthesis in S. cerevisiae and S. pombe cells or in cultured human fibroblasts by treatment with the 3 hydroxy-3-methylglutaryl coenzyme A reductase inhibitor lovastatin resulted in elevated levels of squalene synthetase mRNA in all three cell types. PMID- 8474437 TI - Functional analysis of a stable transcription arrest site in the first intron of the murine adenosine deaminase gene. AB - Transcription arrest plays a role in regulating the expression of a number of genes, including the murine adenosine deaminase (ADA) gene. We have previously identified two prominent arrest sites at the 5' end of the ADA gene: one in the first exon and one in the first intron (J. W. Innis and R. E. Kellems, Mol. Cell. Biol. 11:5398-5409, 1991). Here we report the functional characterization of the intron 1 arrest site, located 137 to 145 nucleotides downstream of the cap site. We have determined, using gel filtration, that the intron 1 arrest site is a stable RNA polymerase II pause site and that the transcription elongation factor SII promotes read-through at this site. Additionally, the sequence determinants for the pause are located within a 37-bp fragment encompassing this site (+123 to +158) and can direct transcription arrest in an orientation-dependent manner in the context of the ADA and adenovirus major late promoters. Specific point mutations in this region increase or decrease the relative pausing efficiency. We also show that the sequence determinants for transcription arrest can function when placed an additional 104 bp downstream of their natural position. PMID- 8474438 TI - NAB2: a yeast nuclear polyadenylated RNA-binding protein essential for cell viability. AB - A variety of nuclear ribonucleoproteins are believed to associate directly with nascent RNA polymerase II transcripts and remain associated during subsequent nuclear RNA processing reactions, including pre-mRNA polyadenylation and splicing as well as nucleocytoplasmic mRNA transport. To investigate the functions of these proteins by using a combined biochemical and genetic approach, we have isolated nuclear polyadenylated RNA-binding (NAB) proteins from Saccharomyces cerevisiae. Living yeast cells were irradiated with UV light to covalently cross link proteins intimately associated with RNA in vivo. Polyadenylated RNAs were then selectively purified, and the covalent RNA-protein complexes were used to elicit antibodies in mice. Both monoclonal and polyclonal antibodies which detect a variety of NAB proteins were prepared. Here we characterize one of these proteins, NAB2. NAB2 is one of the major proteins associated with nuclear polyadenylated RNA in vivo, as detected by UV light-induced cross-linking. Cellular immunofluorescence, using both monoclonal and polyclonal antibodies, demonstrates that the NAB2 protein is localized within the nucleus. The deduced primary structure of NAB2 indicates that it is composed of at least two distinct types of RNA-binding motifs: (i) an RGG box recently described in a variety of heterogeneous nuclear RNA-, pre-rRNA-, mRNA-, and small nucleolar RNA-binding proteins and (ii) CCCH motif repeats related to the zinc-binding motifs of the largest subunit of RNA polymerases I, II, and III. In vitro RNA homopolymer/single-stranded DNA binding studies indicate that although both the RGG box and CCCH motifs bind poly(G), poly(U), and single-stranded DNA, the CCCH motifs also bind to poly(A). NAB2 is located on chromosome VII within a cluster of ribonucleoprotein genes, and its expression is essential for cell growth. PMID- 8474439 TI - Multiple regulatory elements contribute differentially to muscle creatine kinase enhancer activity in skeletal and cardiac muscle. AB - We have used transient transfections in MM14 skeletal muscle cells, newborn rat primary ventricular myocardiocytes, and nonmuscle cells to characterize regulatory elements of the mouse muscle creatine kinase (MCK) gene. Deletion analysis of MCK 5'-flanking sequence reveals a striated muscle-specific, positive regulatory region between -1256 and -1020. A 206-bp fragment from this region acts as a skeletal muscle enhancer and confers orientation-dependent activity in myocardiocytes. A 110-bp enhancer subfragment confers high-level expression in skeletal myocytes but is inactive in myocardiocytes, indicating that skeletal and cardiac muscle MCK regulatory sites are distinguishable. To further delineate muscle regulatory sequences, we tested six sites within the MCK enhancer for their functional importance. Mutations at five sites decrease expression in skeletal muscle, cardiac muscle, and nonmuscle cells. Mutations at two of these sites, Left E box and MEF2, cause similar decreases in all three cell types. Mutations at three sites have larger effects in muscle than nonmuscle cells; an A/T-rich site mutation has a pronounced effect in both striated muscle types, mutations at the MEF1 (Right E-box) site are relatively specific to expression in skeletal muscle, and mutations at the CArG site are relatively specific to expression in cardiac muscle. Changes at the AP2 site tend to increase expression in muscle cells but decrease it in nonmuscle cells. In contrast to reports involving cotransfection of 10T1/2 cells with plasmids expressing the myogenic determination factor MyoD, we show that the skeletal myocyte activity of multimerized MEF1 sites is 30-fold lower than that of the 206-bp enhancer. Thus, MyoD binding sites alone are not sufficient for high-level expression in skeletal myocytes containing endogenous levels of MyoD and other myogenic determination factors. PMID- 8474440 TI - Zebra fish myc family and max genes: differential expression and oncogenic activity throughout vertebrate evolution. AB - To gain insight into the role of Myc family oncoproteins and their associated protein Max in vertebrate growth and development, we sought to identify homologs in the zebra fish (Brachydanio rerio). A combination of a polymerase chain reaction-based cloning strategy and low-stringency hybridization screening allowed for the isolation of zebra fish c-, N-, and L-myc and max genes; subsequent structural characterization showed a high degree of conservation in regions that encode motifs of known functional significance. On the functional level, zebra fish Max, like its mammalian counterpart, served to suppress the transformation activity of mouse c-Myc in rat embryo fibroblasts. In addition, the zebra fish c-myc gene proved capable of cooperating with an activated H-ras to effect the malignant transformation of mammalian cells, albeit with diminished potency compared with mouse c-myc. With respect to their roles in normal developing tissues, the differential temporal and spatial patterns of steady state mRNA expression observed for each zebra fish myc family member suggest unique functions for L-myc in early embryogenesis, for N-myc in establishment and growth of early organ systems, and for c-myc in increasingly differentiated tissues. Furthermore, significant alterations in the steady-state expression of zebra fish myc family genes concomitant with relatively constant max expression support the emerging model of regulation of Myc function in cellular growth and differentiation. PMID- 8474441 TI - Characterization of cytokine LD78 gene promoters: positive and negative transcriptional factors bind to a negative regulatory element common to LD78, interleukin-3, and granulocyte-macrophage colony-stimulating factor gene promoters. AB - Cytokine LD78 is a human counterpart of the mouse macrophage inflammatory protein 1 alpha/hematopoietic stem cell inhibitor. Promoters of the LD78 alpha and LD78 beta genes showed similar inducible activities in two leukemic cell lines, K562 and Jurkat, but the induction mechanisms differed between the two cell lines. Further characterization of the LD78 alpha promoter indicated that multiple positive and negative regulatory elements are present, some of which are differentially required for induction and repression of the promoter activity in different cells. One of the negative regulatory elements, ICK-1, functioned in both cell lines in the absence and presence of stimulation and was shown to be a recognition site for positive and negative transcriptional factors. This ICK-1 element contained a direct repeat, and similar repeats were also found in the negative regulatory elements of hematopoietic growth factor interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoters. Nuclear extracts from K562 and Jurkat cells formed several protein-DNA complexes with the LD78 alpha ICK-1 element, one of which was also observed with the IL-3 and GM-CSF ICK-1 elements. Results from in vivo and in vitro analyses suggested that the protein forming this complex functions as a negative factor. The binding affinity of this protein, ICK-1A, to the LD78 alpha ICK-1 element was low and was significantly affected by the incubation temperature and the salt concentration in the binding buffer. ICK-1B, another protein bound specifically by the LD78 alpha ICK-1 element, was shown to be a positive factor important for induction of the promoter. These results suggested that ICK-1A plays an important role in balanced expression of LD78, IL-3, and GM-CSF during hematopoietic cell growth and differentiation. PMID- 8474442 TI - (CT)n (GA)n repeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26 gene. AB - Previous analysis of the hsp26 gene of Drosophila melanogaster has shown that in addition to the TATA box and the proximal and distal heat shock elements (HSEs) (centered at -59 and -340, relative to the start site of transcription), a segment of (CT)n repeats at -135 to -85 is required for full heat shock inducibility (R.L. Glaser, G.H. Thomas, E.S. Siegfried, S.C.R. Elgin, and J.T. Lis, J. Mol. Biol. 211:751-761, 1990). This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) sites (Q. Lu, L.L. Wallrath, B.D. Allan, R.L. Glaser, J.T. Lis, and S.C.R. Elgin, J. Mol. Biol. 225:985-998, 1992). Inspection of the sequences upstream of hsp26 has revealed an additional (CT)n element at -347 to -341, adjacent to the distal HSE. We have analyzed the contribution of this distal (CT)n element (-347 to -341), the proximal (CT)n element (-135 to -85), and the two HSEs both to the formation of the chromatin structure and to heat shock inducibility. hsp26 constructs containing site-directed mutations, deletions, substitutions, or rearrangements of these sequence elements have been fused in frame to the Escherichia coli lacZ gene and reintroduced into the D. melanogaster genome by P element-mediated germ line transformation. Chromatin structure of the transgenes was analyzed (prior to gene activation) by DNase I or restriction enzyme treatment of isolated nuclei, and heat-inducible expression was monitored by measuring beta-galactosidase activity. The results indicate that mutations, deletions, or substitutions of either the distal or the proximal (CT)n element affect the chromatin structure and heat-inducible expression of the transgenes. These (CT)n repeats are associated with a nonhistone protein(s) in vivo and are bound by a purified Drosophila protein, the GAGA factor, in vitro. In contrast, the HSEs are required for heat-inducible expression but play only a minor role in establishing the chromatin structure of the transgenes. Previous analysis indicates that prior to heat shock, these HSEs appear to be free of protein. Our results suggest that GAGA factor, an abundant protein factor required for normal expression of many Drosophila genes, and heat shock factor, a specific transcription factor activated upon heat shock, play distinct roles in gene regulation: the GAGA factor establishes and/or maintains the DH sites prior to heat shock induction, while the activated heat shock factor recognizes and binds HSEs located within the DH sites to trigger transcription. PMID- 8474443 TI - In Xenopus laevis, the product of a developmentally regulated mRNA is structurally and functionally homologous to a Saccharomyces cerevisiae protein involved in translation fidelity. AB - We have performed a differential screen of a Xenopus egg cDNA library and selected two clones (Cl1 and Cl2) corresponding to mRNA which are specifically adenylated and recruited into polysomes after fertilization. Sequence analysis of Cl1 reveals that the corresponding protein is 67.5% identical (83% similar) to the product of the Saccharomyces cerevisiae SUP45 (also called SUP1 or SAL4) gene. This gene, when mutated, is an omnipotent suppressor of nonsense codons. When expressed in a sup45 mutant, the Xenopus Cl1 cDNA was able to suppress sup45 related phenotypes, showing that the structural homology reflects a functional homology. Our discovery of a structural and functional homolog in Xenopus cells implies that the function of SUP45 is not restricted to lower eukaryotes and that the SUP45 protein may perform a crucial cellular function in higher eukaryotes. PMID- 8474444 TI - Yeast ribosomal protein L1 is required for the stability of newly synthesized 5S rRNA and the assembly of 60S ribosomal subunits. AB - Ribosomal protein L1 from Saccharomyces cerevisiae binds 5S rRNA and can be released from intact 60S ribosomal subunits as an L1-5S ribonucleoprotein (RNP) particle. To understand the nature of the interaction between L1 and 5S rRNA and to assess the role of L1 in ribosome assembly and function, we cloned the RPL1 gene encoding L1. We have shown that RPL1 is an essential single-copy gene. A conditional null mutant in which the only copy of RPL1 is under control of the repressible GAL1 promoter was constructed. Depletion of L1 causes instability of newly synthesized 5S rRNA in vivo. Cells depleted of L1 no longer assemble 60S ribosomal subunits, indicating that L1 is required for assembly of stable 60S ribosomal subunits but not 40S ribosomal subunits. An L1-5S RNP particle not associated with ribosomal particles was detected by coimmunoprecipitation of L1 and 5S rRNA. This pool of L1-5S RNP remained stable even upon cessation of 60S ribosomal subunit assembly by depletion of another ribosomal protein, L16. Preliminary results suggest that transcription of RPL1 is not autogenously regulated by L1. PMID- 8474445 TI - Action of spontaneously produced beta interferon in differentiation of embryonal carcinoma cells through an autoinduction mechanism. AB - In the current study, we have addressed the role of interferons (IFNs) in controlling the differentiation of pluripotent P19 embryonal carcinoma (EC) cells. Blocking IFN activity in the culture medium of differentiating cells with antibodies leads to a strong decrease in the degree of differentiation. The antibodies are active for a relatively short time. During this time, IFN-beta mRNA can be detected in the differentiating cells, as can increases of IFN stimulation response element-binding activity and NF-KB. The timing of IFN action also coincides with the accumulation of cytoplasmic double-stranded RNA (dsRNA) and with a drop in dsRNA unwindase-modificase activity. A model for the involvement of autoinduction of IFN by intracellular dsRNA in the control of differentiation in this system is presented. PMID- 8474446 TI - Mechanism of c-myc regulation by c-Myb in different cell lineages. AB - Activation of the murine c-myc promoter by murine c-Myb protein was examined in several cell lines by using a transient expression system in which Myb expression vectors activate the c-myc promoter linked to a chloramphenicol acetyltransferase reporter gene or a genomic beta-globin gene. S1 nuclease protection analyses confirmed that the induction of c-myc by c-Myb was transcriptional and affected both P1 and P2 start sites in a murine T-cell line, EL4, and a myelomonocytic line, WEHI-3. Mutational analyses of the c-myc promoter revealed that two distinct regions could confer Myb responsiveness in two T-cell lines, a distal site upstream of P1 and a proximal site within the first noncoding exon. In contrast, only the proximal site was required for other cell lineages examined. Five separate Myb-binding sites were located in this proximal site and found to be important for c-Myb trans activation. DNA binding was necessary for c-myc activation, as shown by the loss of function associated with mutation of Myb's DNA-binding domain and by trans-dominant repressor activity of the DNA binding, trans-activation-defective mutant. The involvement of additional protein factors was addressed by inhibiting protein synthesis with cycloheximide in a conditional expression system in which the activity of presynthesized Myb was under the control of estrogen. These experiments indicate that de novo synthesis of additional proteins was not necessary for c-myc trans activation. Together these data reveal two cell lineage-dependent pathways by which c-Myb regulates c-myc; however, both pathways are mechanistically indistinguishable in that direct DNA binding by Myb is required for activating c-myc whereas neither de novo protein synthesis nor other labile proteins are necessary. PMID- 8474447 TI - Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis. AB - Casein kinase I is an acidotropic protein kinase class that is widely distributed among eukaryotic cell types. In the yeast Saccharomyces cerevisiae, the casein kinase I isoform encoded by the gene pair YCK1 and YCK2 is a 60- to 62-kDa membrane-associated form. The Yck proteins perform functions essential for growth and division; either alone supports growth, but loss of function of both is lethal. We report here that casein kinase I-like activity is associated with a soluble Yck2-beta-galactosidase fusion protein in vitro and that thermolabile protein kinase activity is exhibited by a protein encoded by fusion of a temperature-sensitive yck2 allele with lacZ. Cells carrying the yck2-2ts allele arrest at restrictive temperature with multiple, elongated buds containing multiple nuclei. This phenotype suggests that the essential functions of the Yck proteins include roles in bud morphogenesis, possibly in control of cell growth polarity, and in cytokinesis or cell separation. Further, a genetic relationship between the yck2ts allele and deletion of CDC55 indicates that the function of Yck phosphorylation may be related to that of protein phosphatase 2A activity. PMID- 8474448 TI - The product of the EMS1 gene, amplified and overexpressed in human carcinomas, is homologous to a v-src substrate and is located in cell-substratum contact sites. AB - We have previously identified two genes (EMS1 and PRAD1/cyclin D1) in the chromosome 11q13 region that are frequently coamplified and overexpressed in human breast cancer and in squamous cell carcinomas of the head and neck (E. Schuuring, E. Verhoeven, W.J. Mooi, and R.J.A.M. Michalides, Oncogene 7:355-361, 1992). We now report on the characterization of the 80/85-kDa protein that is encoded by the EMS1 gene. Amino acid sequence comparison shows a high homology (85%) to a chicken protein that was recently identified as a substrate for the src oncogene (H. Wu, A.B. Reynolds, S.B. Kanner, R.R. Vines, and J.T. Parsons, Mol. Cell. Biol. 11:5113-5124, 1991). Immunocytochemistry reveals that in epithelial cells, the human EMS1 protein is localized mainly in the cytoplasm and, to a very low extent, in protruding leading lamellae of the cell. However, in carcinoma cells that constitutively overexpress the protein as a result of amplification of the EMS1 gene, the protein, except in cytoplasm, accumulates in the podosome-like adherens junctions associated with the cell-substratum contact sites. The protein was not found in intercellular adherens junctions. Our findings, and the previously reported observations in src-transformed chicken embryo fibroblasts, suggest that the EMS1 protein is involved in regulating the interactions between components of adherens-type junctions. Since amplification of the 11q13 region has been associated with an enhanced invasive potential of these tumors, overexpression and concomitant accumulation of the EMS1 protein in the cell-substratum contact sites might, therefore, contribute to the invasive potential of these tumor cells. PMID- 8474449 TI - Cell cycle regulation of the yeast Cdc7 protein kinase by association with the Dbf4 protein. AB - Yeast Cdc7 protein kinase and Dbf4 protein are both required for the initiation of DNA replication at the G1/S phase boundary of the mitotic cell cycle. Cdc7 kinase function is stage-specific in the cell cycle, but total Cdc7 protein levels remained unchanged. Therefore, regulation of Cdc7 function appears to be the result of posttranslational modification. In this study, we have attempted to elucidate the mechanism responsible for achieving this specific execution point of Cdc7. Cdc7 kinase activity was shown to be maximal at the G1/S boundary by using either cultures synchronized with alpha factor or Cdc- mutants or with inhibitors of DNA synthesis or mitosis. Therefore, Cdc7 kinase is regulated by a posttranslational mechanism that ensures maximal Cdc7 activity at the G1/S boundary, which is consistent with Cdc7 function in the cell cycle. This cell cycle-dependent regulation could be the result of association with the Dbf4 protein. In this study, the Dbf4 protein was shown to be required for Cdc7 kinase activity in that Cdc7 kinase activity is thermolabile in vitro when extracts prepared from a temperature-sensitive dbf4 mutant grown under permissive conditions are used. In vitro reconstitution assays, in addition to employment of the two-hybrid system for protein-protein interactions, have demonstrated that the Cdc7 and Dbf4 proteins interact both in vitro and in vivo. A suppressor mutation, bob1-1, which can bypass deletion mutations in both cdc7 and dbf4 was isolated. However, the bob1-1 mutation cannot bypass all events in G1 phase because it fails to suppress temperature-sensitive cdc4 or cdc28 mutations. This indicates that the Cdc7 and Dbf4 proteins act at a common point in the cell cycle. Therefore, because of the common point of function for the two proteins and the fact that the Dbf4 protein is essential for Cdc7 function, we propose that Dbf4 may represent a cyclin-like molecule specific for the activation of Cdc7 kinase. PMID- 8474450 TI - An octamer motif contributes to the expression of the retinoic acid-regulated zinc finger gene Rex-1 (Zfp-42) in F9 teratocarcinoma cells. AB - The message for the zinc finger gene Rex-1 (Zfp-42) is expressed in undifferentiated murine F9 teratocarcinoma cells and embryonic stem cells. Expression of Rex-1 is reduced at the transcriptional level when F9 cells are induced by the addition of retinoic acid (RA) to differentiate. We have isolated genomic DNA for the Rex-1 gene (Zfp-42), characterized the gene's structure, and mapped the gene to mouse chromosome 8. Promoter elements contributing to the regulation of the Rex-1 promoter in F9 cells have been identified. A region required for Rex-1 promoter activity in F9 stem cells contains an octamer motif (ATTTGCAT) which is a binding site for octamer transcription factor members of the POU domain family of DNA-binding proteins. Rex-1 reporter plasmids including this octamer site also exhibited reduced expression in F9 cells treated with RA. Thus, the octamer motif is a regulatory element required for the activity of the Rex-1 promoter in F9 stem cells, and this motif contributes to the negative regulation by RA of the transcription of the Rex-1 gene. As an initial confirmation of the in vivo relevance of the isolated fragment, a larger Rex-1 promoter fragment, also containing the octamer site, was able to promote expression of the bacterial lacZ gene in mouse embryos at the morula stage. PMID- 8474451 TI - Mouse beta-globin DNA-binding protein B1 is identical to a proto-oncogene, the transcription factor Spi-1/PU.1, and is restricted in expression to hematopoietic cells and the testis. AB - The hematopoietic-specific DNA-binding protein B1 binds to the DNA consensus sequence AAAGRGGAARYG located twice in intervening sequence 2 of both of the mouse beta-globin genes (D. L. Galson and D.E. Housman, Mol. Cell. Biol. 8:381 392, 1988). B1 was cloned by expression of a murine erythroleukemia (MEL) cell cDNA library in transfected COS cells and screening by electrophoretic mobility shift analysis. B1 is identical to the proto-oncogene Spi-1/PU.1 (Spi-1), an ets family member. Protein-DNA contacts are shown to resemble those of the helix-turn helix homeodomain proteins. By Northern (RNA) analysis, we found that Spi-1 mRNA is present at low levels during murine CFU-E maturation and is at least 20-fold higher in uninduced MEL, a transformed proerythroblast-like cell line which contains an activating/transforming insertion of spleen focus-forming virus at the Spi-1 locus. Dimethyl sulfoxide-induced MEL cell differentiation decreases Spi-1 mRNA to approximately 20% of the uninduced level before commitment occurs. In addition to erythroid cells, Spi-1 mRNA is present in B cells, myelomonocytes, and mast cells but not in T cells and nonhematopoietic cell types. In situ hybridization demonstrated Spi-1 mRNA expression in bone marrow, spleen, interstitial nonhepatocytes of the liver, and interstitial nontubular cells of the testis. The Spi-1 locus was mapped on human chromosome 11 to the same interval as ACP2 (lysosomal acid phosphatase), between the anonymous DNA markers D11S33 and D11S14. This region has not yet been found to be associated with a human malignancy. PMID- 8474452 TI - Cloning and characterization of R-PTP-kappa, a new member of the receptor protein tyrosine phosphatase family with a proteolytically cleaved cellular adhesion molecule-like extracellular region. AB - We describe a new member of the receptor protein tyrosine phosphatase family, R PTP-kappa, cDNA cloning predicts that R-PTP-kappa is synthesized from a precursor protein of 1,457 amino acids. Its intracellular domain displays the classical tandemly repeated protein tyrosine phosphatase homology, separated from the transmembrane segment by an uncharacteristically large juxta-membrane region. The extracellular domain of the R-PTP-kappa precursor protein contains an immunoglobulin-like domain and four fibronectin type III-like repeats, preceded by a signal peptide and a region of about 150 amino acids with similarity to the Xenopus A5 antigen, a putative neuronal recognition molecule (S. Takagi, T. Hsrata, K. Agata, M. Mochii, G. Eguchi, and H. Fujisawa, Neuron 7:295-307, 1991). Antibodies directed against the intra- and extracellular domains reveal that the R-PTP-kappa precursor protein undergoes proteolytic processing, following which both cleavage products remain associated. By site-directed mutagenesis, the likely cleavage site was shown to be a consensus sequence for cleavage by the processing endopeptidase furin, located in the fourth fibronectin type III-like repeat. In situ hybridization analysis indicates that expression of R-PTP-kappa in the central nervous system is developmentally regulated, with highest expression seen in actively developing areas and, in the adult, in areas capable of developmental plasticity such as the hippocampal formation and cerebral cortex. The mouse R-PTP-kappa gene maps to chromosome 10, at approximately 21 centimorgans from the centromere. PMID- 8474453 TI - Tissue-specific expression of human CD4 in transgenic mice. AB - The gene for the human CD4 glycoprotein, which serves as the receptor for human immunodeficiency virus type 1, along with approximately 23 kb of sequence upstream of the translational start site, was cloned. The ability of 5' flanking sequences to direct tissue-specific expression was tested in cell culture and in transgenic mice. A 5' flanking region of 6 kb was able to direct transcription of the CD4 gene in NIH 3T3 cells but did not result in detectable expression in the murine T-cell line EL4 or in four lines of transgenic mice. A larger 5' flanking region of approximately 23 kb directed high-level CD4 transcription in the murine T-cell line EL4 and in three independent lines of transgenic mice. Human CD4 expression in all tissues analyzed was tightly correlated with murine CD4 expression; the highest levels of human CD4 RNA expression were found in the thymus and spleen, with relatively low levels detected in other tissues. Expression of human CD4 protein in peripheral blood mononuclear cells was examined by flow cytometry in these transgenic animals and found to be restricted to the murine CD4+ subset of lymphocytes. Human CD4 protein, detected with an anti-human CD4 monoclonal antibody, was present on the surface of 45 to 50% of the peripheral blood mononuclear cells from all transgenic lines. PMID- 8474454 TI - A U5 small nuclear ribonucleoprotein particle protein involved only in the second step of pre-mRNA splicing in Saccharomyces cerevisiae. AB - The PRP18 gene, which had been identified in a screen for pre-mRNA splicing mutants in Saccharomyces cerevisiae, has been cloned and sequenced. Yeast strains bearing only a disrupted copy of PRP18 are temperature sensitive for growth; even at a low temperature, they grow extremely slowly and do not splice pre-mRNA efficiently. This unusual temperature sensitivity can be reproduced in vitro; extracts immunodepleted of PRP18 are temperature sensitive for the second step of splicing. The PRP18 protein has been overexpressed in active form in Escherichia coli and has been purified to near homogeneity. Antibodies directed against PRP18 precipitate the U4/U5/U6 small nuclear ribonucleoprotein particle (snRNP) from yeast extracts. From extracts depleted of the U6 small nuclear RNA (snRNA), the U4 and U5 snRNAs can be immunoprecipitated, while no snRNAs can be precipitated from extracts depleted of the U5 snRNA. PRP18 therefore appears to be primarily associated with the U5 snRNP. The antibodies against PRP18 inhibit the second step of pre-mRNA splicing in vitro. Together, these results imply that the U5 snRNP plays a role in the second step of splicing and suggest a model for the action of PRP18. PMID- 8474455 TI - Localization of a bidirectional DNA replication origin in the native locus and in episomally amplified murine adenosine deaminase loci. AB - Gene amplification is frequently mediated by the initial production of acentric, autonomously replicating extrachromosomal elements. The 4,000 extrachromosomal copies of the mouse adenosine deaminase (ADA) amplicon in B-1/50 cells initiate their replication remarkably synchronously in early S phase and at approximately the same time as the single-copy chromosomal locus from which they were derived. The abundance of ADA sequences and favorable replication timing characteristics in this system led us to determine whether DNA replication initiates in ADA episomes within a preferred region and whether this region is the same as that used at the corresponding chromosomal locus prior to amplification. This study reports the detection and localization of a discrete set of DNA fragments in the ADA amplicon which label soon after release of synchronized B-1/50 cells into S phase. A switch in template strand complementarity of Okazaki fragments, indicative of the initiation of bidirectional DNA replication, was found to lie within the same region. This putative replication origin is located approximately 28.5 kbp upstream of the 5' end of the ADA gene. The same region initiated DNA replication in the single-copy ADA locus of the parental cells. These analyses provide the first evidence that the replication of episomal intermediates involved in gene amplification initiates within a preferred region and that the same region is used to initiate DNA synthesis within the native locus. PMID- 8474456 TI - Both LyF-1 and an Ets protein interact with a critical promoter element in the murine terminal transferase gene. AB - Terminal deoxynucleotidyltransferase (TdT) is a template-independent DNA polymerase that is expressed transiently during the earliest stages of B- and T cell ontogeny. Previously, we characterized the promoter for the murine TdT gene and identified a novel DNA-binding protein, called LyF-1, that interacts with a DNA sequence element found to be critical for transcriptional activity in lymphoid cell lines. Here, we present a more detailed analysis of this 30-bp control element, called the TdT D' element, which is centered approximately 60 bp upstream of the transcription start site. We found that both the murine and human D' elements are recognized by multiple proteins, including LyF-1 and at least two Ets family proteins, Ets-1 and Fli-1. Additional protein-DNA interactions were identified through studies using unfractionated nuclear extracts, in which the D' element was apparently incorporated into a multiprotein complex, possibly containing an Ets protein as a core component. By analyzing a series of substitution mutations, two adjacent binding sites for LyF-1 were identified in the murine D' element, with the Ets protein binding site closely coinciding with the proximal, lower-affinity LyF-1 site. Transient transfection analysis with these mutations revealed that only a 10-bp region, containing precisely the Ets and proximal LyF-1 binding sites, was needed for D' activity. These results suggest an important role for an Ets family protein in the expression of the TdT gene. The role of LyF-1 is less clear; it might act in conjunction with the Ets protein bound at the D' element or it might be unnecessary for D' activity. PMID- 8474457 TI - Modulation of exon skipping and inclusion by heterogeneous nuclear ribonucleoprotein A1 and pre-mRNA splicing factor SF2/ASF. AB - The essential splicing factor SF2/ASF and the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) modulate alternative splicing in vitro of pre mRNAs that contain 5' splice sites of comparable strengths competing for a common 3' splice site. Using natural and model pre-mRNAs, we have examined whether the ratio of SF2/ASF to hnRNP A1 also regulates other modes of alternative splicing in vitro. We found that an excess of SF2/ASF effectively prevents inappropriate exon skipping and also influences the selection of mutually exclusive tissue specific exons in natural beta-tropomyosin pre-mRNA. In contrast, an excess of hnRNP A1 does not cause inappropriate exon skipping in natural constitutively or alternatively spliced pre-mRNAs. Although hnRNP A1 can promote alternative exon skipping, this effect is not universal and is dependent, e.g., on the size of the internal alternative exon and on the strength of the polypyrimidine tract in the preceding intron. With appropriate alternative exons, an excess of SF2/ASF promotes exon inclusion, whereas an excess of hnRNP A1 causes exon skipping. We propose that in some cases the ratio of SF2/ASF to hnRNP A1 may play a role in regulating alternative splicing by exon inclusion or skipping through the antagonistic effects of these proteins on alternative splice site selection. PMID- 8474458 TI - Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif. AB - We report characterization of several domains within the 5' flanking region of the olfactory marker protein (OMP) gene that may participate in regulating transcription of this and other olfactory neuron-specific genes. Analysis by electrophoretic mobility shift assay and DNase I footprinting identifies two regions that contain a novel sequence motif. Interactions between this motif and nuclear proteins were detected only with nuclear protein extracts derived from olfactory neuroepithelium, and this activity is more abundant in olfactory epithelium enriched in immature neurons. We have designated a factor(s) involved in this binding as Olf-1. The Olf-1-binding motif consensus sequence was defined as TCCCC(A/T)NGGAG. Studies with transgenic mice indicate that a 0.3-kb fragment of the OMP gene containing one Olf-1 motif is sufficient for olfactory tissue specific expression of the reporter gene. Some of the other identified sequence motifs also interact specifically with olfactory nuclear protein extracts. We propose that Olf-1 is a novel, olfactory neuron-specific trans-acting factor involved in the cell-specific expression of OMP. PMID- 8474459 TI - Architecture of a yeast U6 RNA gene promoter. AB - The promoters of vertebrate and yeast U6 small nuclear RNA genes are structurally dissimilar, although both are recognized by RNA polymerase III. Vertebrate U6 RNA genes have exclusively upstream promoters, while the U6 RNA gene from the yeast Saccharomyces cerevisiae (SNR6) has internal and downstream promoter elements that match the tRNA gene intragenic A- and B-block elements, respectively. Substitution of the SNR6 A or B block greatly diminished U6 RNA accumulation in vivo, and a subcellular extract competent for RNA polymerase III transcription generated nearly identical DNase I protection patterns over the SNR6 downstream B block and a tRNA gene intragenic B block. We conclude that the SNR6 promoter is functionally similar to tRNA gene promoters, although the effects of extragenic deletion mutations suggest that the downstream location of the SNR6 B block imposes unique positional constraints on its function. Both vertebrate and yeast U6 RNA genes have an upstream TATA box element not normally found in tRNA genes. Substitution of the SNR6 TATA box altered the site of transcription initiation in vivo, while substitution of sequences further upstream had no effect on SNR6 transcription. We present a model for the SNR6 transcription complex that explains these results in terms of their effects on the binding of transcription initiation factor TFIIIB. PMID- 8474460 TI - Positive and negative modulation of Jun action by thyroid hormone receptor at a unique AP1 site. AB - We have characterized the putative AP1 site in the backbone of pUC plasmids and found unique regulatory effects. The site, which mapped to a 19-bp region around nucleotide 37, conferred transcriptional activation by Jun or Jun/Fos that was boosted up to fivefold by unliganded thyroid hormone receptor (TR). Thyroid hormone changed potentiation of the Jun response by TR into repression. Although the plasmid sequence is a near-perfect consensus AP1 site, the perfect consensus AP1 site from the human collagenase promoter did not show the same effects. Deletion of the ligand binding domain of the TR eliminated the ability of the receptor to boost Jun activity, and deletion, mutation, or changes in specificity of the DNA binding domain eliminated both its ability to potentiate Jun activity and repress with hormone. In vitro Jun/Fos complexes bound the operative plasmid fragment, and the presence of TR interfered very little with Jun/Fos binding activity. Protein interaction studies in the absence of DNA showed that TR bound Jun protein in solution either in the presence or in the absence of hormone. These observations suggest a mechanism for synergy and repression by TR through modulation of Jun activity: positive when TR is unliganded, and negative when hormone is bound. They also suggest that the presence of the plasmid element can confound studies of the regulation of linked promoters. PMID- 8474461 TI - Expression of the transcriptional activator LAC9 (KlGAL4) in Kluyveromyces lactis is controlled by autoregulation. AB - The concentration of the transcriptional activator LAC9 (KlGAL4) of Kluyveromyces lactis is moderately regulated by the carbon source as is the case for GAL4, its homolog in Saccharomyces cerevisiae. Expression of the LAC9 gene is induced about twofold in galactose. This induction is due to autoregulation. The LAC9 gene product binds to a low-affinity binding site in the LAC9 promoter and moderately activates transcription in response to galactose above a basal level. As for the LAC9-controlled metabolic genes, induction of LAC9 is inhibited in the presence of glucose. This inhibition of induction is a prerequisite for glucose repression of the lactose-galactose metabolic pathway. On the other hand, induced LAC9 levels are required for optimal growth on galactose, since mutating the LAC9 binding site in the LAC9 promoter resulted in poor growth and reduced expression of LAC9-controlled genes. Thus, in addition to the GAL80-dependent regulation by protein-protein interaction, the regulation of LAC9 gene expression is an important parameter in determining carbon source control of the LAC-GAL regulon. Although the mode of control is different, the pattern of LAC9 gene regulation resembles that of the S. cerevisiae GAL4 gene, being lower in glucose and glucose galactose than in galactose. PMID- 8474462 TI - The ADP/ATP carrier is the 32-kilodalton receptor for an NH2-terminally myristylated src peptide but not for pp60src polypeptide. AB - Membrane binding of pp60src is initiated via its myristylated NH2 terminus. To identify a candidate pp60src docking protein or receptor in the membrane, a radiolabelled peptide corresponding to the pp60src NH2-terminal membrane binding domain was cross-linked to fibroblast membranes and found to specifically label a 32-kDa protein. This protein was purified by appending an affinity tag to the peptide probe so that the cross-linked complex could be isolated via affinity chromatography. Microsequencing indicated that the 32-kDa protein was the mitochondrial ADP/ATP carrier (AAC). This result was further confirmed by the ability of an antibody to the AAC to immunoprecipitate the cross-linked complex, by the ability of certain inhibitors of the AAC to block cross-linking, and by membrane fractionation to show that complex formation occurred essentially exclusively in the mitochondrial fraction. While the AAC bound the myristyl-src peptide in a specific manner both in vitro and in vivo, its localization to the inner membrane of the mitochondrion precludes its being a pp60src binding protein. An analysis of pp60v-src binding in vitro was consistent with this expectation. Thus, use of a myristyl-src peptide revealed an unexpected and previously unidentified binding capacity of the AAC, most likely related to the ability of long-chain fatty acyl coenzyme As to serve as AAC inhibitors. The amphipathic nature of the pp60src NH2 terminus suggests alternative strategies for uncovering pp60src membrane binding species. PMID- 8474463 TI - Overexpression of Myc suppresses CCAAT transcription factor/nuclear factor 1 dependent promoters in vivo. AB - Overexpression of Myc in cells can suppress the transcription of specific genes. Because several of these genes have common transcriptional regulatory elements, we investigated the possibility that this effect of Myc is mediated through a specific transcription factor. In vitro DNA-binding assays detect only one form of CCAAT transcription factor/nuclear factor 1 (CTF/NF-1) in quiescent 3T3-L1 cells. By contrast, quiescent 3T3-L1 cells that stably overexpress either c-Myc or N-Myc contain at least three forms of CTF/NF-1. Biochemical characterization of the various CTF/NF-1 forms showed that they have the same native molecular weight but differ in charge density. The more negatively charged CTF/NF-1 forms present in Myc-overexpressing cells are converted into that found in normal cells by treatment with acid phosphatase, suggesting that they represent a more phosphorylated form of the CTF/NF-1 protein. The various CTF/NF-1 forms have a similar DNA-binding affinity. Transfection experiments demonstrated that transcription from CTF/NF-1-dependent promoters is specifically suppressed in cells that stably overexpress c-Myc. This effect requires CTF/NF-1 binding. CTF/NF-1-dependent promoter activity is also suppressed in 3T3-L1 cells during active growth (relative to the quiescent state). Interestingly, actively growing 3T3-L1 cells contain forms of CTF/NF-1 similar to those in quiescent cells that stably overexpress c-Myc. Thus, the CTF/NF-1 forms present in cells that express high amounts of c-Myc correlate with a lower transcription rate of CTF/NF-1 dependent promoters in vivo. Our results provide a basis for the suppression of specific gene transcription by c-Myc. PMID- 8474465 TI - [Treatment of secondary infections in symptomatic HIV-infections in childhood]. AB - Treatment of secondary infections in HIV infected children represents a problem of increasing importance in several children's hospitals. As it is unlikely that the AIDS-problem will be solved by itself within the next years it seems reasonable to summarize our current knowledge about opportunistic infections in order to establish standards for therapy. We will mainly focus on microorganisms endemic in Germany. PMID- 8474464 TI - The orphan receptor Rev-ErbA alpha activates transcription via a novel response element. AB - Rev-ErbA alpha (Rev-Erb) is a nuclear hormone receptor-related protein encoded on the opposite strand of the alpha-thyroid hormone receptor (TR) gene. This unusual genomic arrangement may have a regulatory role, but the conservation of human and rodent Rev-Erb amino acid sequences suggests that the protein itself has an important function, potentially as a sequence-specific transcriptional regulator. However, despite its relationship to the TR, Rev-Erb bound poorly to TR binding sites. To determine its DNA-binding specificity in an unbiased manner, Rev-Erb was synthesized in Escherichia coli, purified, and used to select specific binding-sites from libraries of random double-stranded DNA sequences. We found that Rev-Erb binds to a unique site consisting of a specific 5-bp A/T-rich sequence adjacent to a TR half-site. Rev-Erb contacts this entire asymmetric 11 bp sequence, which is the longest nonrepetitive element specifically recognized by a member of the thyroid/steroid hormone receptor superfamily, and mutations in either the A/T-rich or TR half-site regions abolished specific binding. The binding specificity of wild-type Rev-Erb was nearly identical to that of C- and N terminally truncated forms. This binding was not enhanced by retinoid X receptor, TR, or other nuclear proteins, none of which formed heterodimers with Rev-Erb. Rev-Erb also appeared to bind to the selected site as a monomer. Furthermore, Rev Erb activates transcription through this binding site even in the absence of exogenous ligand. Thus, Rev-Erb is a transcriptional activator whose properties differ dramatically from those of classical nuclear hormone receptors, including the TR encoded on the opposite strand of the same genomic locus. PMID- 8474466 TI - [Chronic metabolic alkalosis in a newborn infant caused by congenital chloride diarrhea]. AB - The case of a female preterm infant (gestational age 36 weeks) is described, who presented with abdominal distension, diarrhoea, dehydration and metabolic alkalosis at the fifth day of life. After different diagnostic tests had been performed, congenital chloride diarrhoea was suspected and chloride supplementation was started. However, this diagnosis could not be confirmed, until the measurement of electrolytes in faeces had been improved. Then, we found the typically elevated fecal chloride concentration (130-153 mmol/l) which exceeded the sum of the fecal concentration of sodium (64-90 mmol/l) and potassium (28-35 mmol/l). The chloride supplementation was increased to 6 mmol/kg/d NaCl and 2 mmol/kg/d KCl. The most recent examination at the age of 1 year revealed the girl to be in good clinical condition, with normal growth and psychomotor-development and with no evidence of renal impairment. PMID- 8474467 TI - [Complete trisomy 22]. AB - In a 2 6/12-years-old girl a complete trisomy 22 was verified with the G-banding (CTG-technique). She presented with Pierre-Robin-Sequence, cardiac and renal malformations, craniofacial dysmorphia and psychomotoric retardation as it often occurs in trisomy 22. Additionally, we observed tonic-clonic seizures, remarkable dumbles on both elbows and a clavicular anomaly. PMID- 8474468 TI - [Early infantile malignant osteopetrosis. Experiences with drug therapy]. AB - The autosomal recessive form of osteopetrosis becomes manifest in early infancy and often is lethal during the first decade of life. In an infant diagnosed at the age of eight weeks, a therapy with Calcitriol (Rocaltrol) was initiated with the intention to stimulate the osteoclast activity and to improve the bone marrow insufficiency. During therapy, a massive diarrhoea has been observed as potential and previously undescribed side effect of Calcitriol. Therefore the therapy had to be discontinued. A simultaneous trial with Ca-depleted diet did not show any effect. In the absence of a suitable donor, a bone-marrow transplantation could not be performed. The patient died at the age of five month. PMID- 8474469 TI - [Hemolytic-uremic syndrome in pneumococcal meningitis and infection. Importance of T-transformation]. AB - A 4 month old girl developed a severe hemolytic uremic syndrome (HUS) following pneumococcal sepsis and meningitis. As a result of the hemolytic anemia and thrombocytopenia with associated gastrointestinal bleeding several red blood cell and thrombocyte transfusions became necessary. No plasma was transfused to the patient and all cellular blood components to be transfused were washed thoroughly in order to avoid the administration of eventually dangerous donor anti-T antibodies. Continuous peritoneal dialysis was performed for 23 days until sufficient spontaneous urine production was resumed. From the start of increased hemolysis T-transformation of the patient's red blood cells could be shown; bacterial neuraminidase was proven in the patient's serum, which could be neutralized in vitro by a commercial intravenous IgG preparation. The direct Coombs-Test was negative and no significant amounts of anti-T antibodies were detectable in the patient's serum at any stage of the disease. Our observation suggest that the T-transformation itself has caused the increased hemolysis and not an antigen-antibody (T-anti-T) reaction. In cases of HUS und proven T transformation, intravenous IgG preparations should be tried therapeutically to inhibit the bacterial neuraminidase. PMID- 8474470 TI - [Early detection of critical aortic isthmus stenosis in the neonate]. AB - Between 1985 and 1992 7 newborns with critical coarctation of the aorta were referred with clinical signs of beginning or manifest cardio-vascular shock and subsequently underwent a primary operative correction. All of the children were noticed by their parents as having unspecific clinical symptoms such as poor feeding and tachypnoea. The aim of our clinical effort should be to detect all newborns with critical coarctation of the aorta before manifestation of a cardiogenic shock, i.e. before the complete closure of the ductus arteriosus. This might be possible with a careful clinical examination of the cardio-vascular system between the 3rd and 4th day of life and the correct interpretation of unspecific early symptoms. PMID- 8474471 TI - [Intermediate results of a multicenter study in long-term management of HIV exposed and infected children]. AB - AIM OF THE STUDY: In most cases (about 80%) the HIV-infection of children is acquired during pregnancy or birth. Therefore peculiarities for diagnostic procedures and in the natural course of the disease can be expected if compared to AIDS acquired at adult age. Further interesting questions are the frequency of the (vertical) transmission from the infected mother to the child, the influence of mother- and/or child-related factors as well as the method of delivery on this transmission frequency. METHODS: In order to answer these questions the children of HIV-infected mothers since April 1, 1988 have been examined virologically, immunologically and clinically since birth by 6 study centers according to a standard protocol. The pregnancy data of the mothers have been documented, according to uniform criteria. Pre- or perinatally infected children not known to be antibody-positive at birth have been separately analysed. RESULTS: The frequency of pre/perinatal transmission from the mother to the child is 15.3%, the elective caesarean section seems to lower the transmission rate. Mother and/or infant related cofactors of the transmission could not be defined. In comparison to the control groups of the intrauterine HIV-exposed but not infected children, at birth the HIV-infected children were clinically and immunologically not ill. During their first months some of the infected children had a significant increase of serum IgG. Oral candidiasis, chronic recurrent diarrhoea and bacterial infections are indicator symptoms of beginning HIV-disease. The Minimum-AIDS-Prevalence in the child's first year is 24%. The relatively late AIDS manifestation (3.7 years) and the average value of 28 months of survival in retrospective observed children were a remarkable result. CONCLUSION: In general, the course of an HIV-infection in children of HIV-positive women in Germany seems to be comparable to results in other countries. The frequency of transmission from mother to child is relatively low (15.3%) and is an important result for maternity care. The caesarean section should be considered. The course of pregnancy must be examined more subtly in order to find out the still unclear causes of transmission. The Minimum-AIDS-Prevalence of 24% and the frequency of HIV-related signs and symptoms of 29% in the child's first year make it necessary to observe these children rather closely during this time. PMID- 8474472 TI - [Prevalence of drugs in meconium]. AB - BACKGROUND: The number of newborn infants with symptoms suggesting drug withdrawal is increasing. As only part of prenatally exposed infants show typical drug withdrawal, and drug-use reported by addicted mothers is often unreliable the prevalence of neonates that were exposed to illicit drugs before birth is unknown. The purpose of this study was to evaluate prospectively the prevalence of drugs in meconium and to define risk factors for intrauterine drug exposure. METHODS: During a period of 4 months meconium was collected twice in 420 nonselected newborn infants. Meconium was analysed with a modified test developed for toxicology screening in urine. Information on pre- and postnatal risk factors including drug-use during pregnancy was obtained. RESULTS: Among 415 mothers four reported illicit drug use and ten licit drug use during late pregnancy. In all these infants meconium drug test was positive. After exclusion of these infants and of five second twins 401 infants with negative drug history remained. 45 of them (11%) had one or two drugs in the meconium: opiate 17x, amphetamine 16x, barbiturate 15x, benzodiazepine 3x, cannabinoid 2x, cocaine 1x (in 9 infants two substances were detected). None was positive for LSD or phencyclidine. The infants with positive drug tests had the following risks compared to those with negative tests: prematurity (odds ratio 2.3, 95% confidence interval 1.3-4.3). Microcephaly or macrocephaly (2.0:1.01-4.1), Apgar-Score below 5 at 1 min (2.4:1.5-5.4), Apgar score below 7 at 10 min (4.0: 1.6-9.9), mother academic (2.8:1.2-6.2). CONCLUSIONS: Newborn infants may have been exposed to illicit drugs in utero even if their mothers deny drug use and even if they do not show withdrawal symptoms. Prematurely born infants and infants with problems in postnatal adaptation have an increased risk of having been exposed to drugs. PMID- 8474473 TI - [Is homeopathy a false doctrine?]. AB - We realize that it is virtually impossible to persuade the convinced practitioners of any of the pseudo-scientific beliefs. Therefore, it is our aim to support those fellow workers and interested laymen, intimidated by the contentions of homeopaths by providing them with relevant facts to counter the mostly absurd claims put forward by practitioners of alternative medicine. 1. The rule of "similarity" is based on incorrect assumptions. 2. Dilution = Dilution A dilution is neither a "potentization" nor a "dynamization" nor an "energyzation". All these expressions are not based on carefully defined notions or concepts but are merely literal creations of homeopaths. It is well known that the "Urtinktur" in addition to producing desired effects possesses a substantial number of undesired side effects. The reader might wonder why only the beneficial effects would be amplified ("potentiated") while all other side effects would happen to be attenuated ("diluted"). 3. The only evidence all practitioners of pseudo medicine can muster to prove the efficacy of their methods are occasional healings following pseudo-medical treatment. PMID- 8474474 TI - [Comments on the contribution by E. Rugo and U. Wahn. In vitro studies of residual allergen activity of hydrolysate nutrition]. PMID- 8474475 TI - [Sizes and body proportions of abused children]. PMID- 8474476 TI - [Procedure in ingestion of batteries]. PMID- 8474477 TI - [Bronchial asthma]. PMID- 8474478 TI - PET study on striatal dopamine D2 receptor changes during the progression of early Parkinson's disease. AB - [11C]Raclopride uptake to dopamine D2 receptors was investigated with positron emission tomography (PET) in patients with early Parkinson's disease at the time of the diagnosis and after a half-year interval. During this progressive period of the disease, the patients received no antiparkinsonian medication. The upregulation of striatal D2 receptors, which was seen in all patients already at the time of the diagnosis, persisted. Although the patients initially showed unilateral disease, they had developed bilateral symptoms by the time of the second PET scan, but the disease was still asymmetric. The present results show that the relative increase in [11C]raclopride uptake in the striatum contralateral to the symptoms as compared with the opposite striatum will be preserved even during the progression of the disease, provided that the symptoms show clear-cut asymmetry. PMID- 8474479 TI - Does tolerance develop to levodopa? Comparison of 2- and 21-H levodopa infusions. AB - To determine if acute tolerance to levodopa develops, we compared the response to 2- and 21-h levodopa infusions with the rate adjusted during the long infusion to yield the same plasma concentration as at the end of the 2-h infusion. The duration of response after discontinuing the long infusions was briefer than after discontinuing the short infusion, suggesting the development of tolerance. Furthermore, dyskinesia severity was greater during long infusions. We conclude that continuous dopaminergic stimulation with levodopa may not offer optimal control of parkinsonism in patients with response fluctuations. PMID- 8474480 TI - Effect of adding the D1 agonist CY 208-243 to chronic bromocriptine treatment. I: Evaluation of motor parameters in relation to striatal catecholamine content and dopamine receptors. AB - A group of four cynomolgus monkeys previously rendered parkinsonian by the toxin 1-methyl-4-phenyl,1,2,3,6-tetrahydropyridine (MPTP) were observed in locomotion cages equipped with photocells during four periods of 7 days during which they received saline or two doses of the D1 agonist CY 208-243. The larger dose of 0.5 mg/kg produced a significant increase in locomotion in three of four animals. A second group of eight monkeys also previously rendered parkinsonian by MPTP and having received no other treatment were given a daily treatment of bromocriptine 1.66 mg/kg orally daily during 4 weeks. In four of the animals, after a week on bromocriptine alone, the D1 agonist CY 208-243 was added in increasing doses of 0.05, 0.1, and 0.5 mg/kg. The motor response as measured by locomotion, hand dexterity, and a disability score improved progressively at least in some of the animals on bromocriptine alone. The addition of CY 208-243 produced a more striking improvement of all three parameters, which appeared to be dose dependent. Biochemical analysis of the brain of these animals plus one control and one MPTP untreated monkey showed a > 90% loss of dopamine in the striatum in six of the eight treated monkeys. Both D2 and D1 dopamine receptors were increased in density by denervation, but both treatments abolished this increase for the D2 receptors while increasing the affinity of the D1 receptors. PMID- 8474481 TI - Sympathetic skin response and R-R interval variation in Parkinson's disease. AB - We investigated autonomic function in patients with idiopathic Parkinson's disease (PD) by measuring sympathetic skin response (SSR) and R-R interval variation (RRIV). Sixty-two PD patients and 62 age-matched normal subjects were recruited. Abnormal SSR was noted in nine (14.5%) PD patients, including three in Stage II, three in Stage III, and three in Stage IV, but not in Stage I patients or normal subjects. Four of these nine patients had postural hypotension. Abnormal SSR was correlated with duration of illness and impotence. In PD patients, abnormal SSR may be due to intermediolateral column dysfunction. After logarithmic transformation and age adjustment, 19 (31.6%) of 60 PD patients had abnormal RRIV during rest and deep breathing. Abnormal RRIV was not related to staging or duration of illness. Patients with constipation had significantly lower RRIV, indicating parasympathetic dysfunction. RRIV was not affected by acute or chronic L-dopa treatment. The agreement between RRIV and SSR in PD patients was poor (kappa = -0.07). It appears that abnormal SSR, but not RRIV, may be associated with more autonomic disturbances in PD patients. PMID- 8474482 TI - Apomorphine test for dopaminergic responsiveness: a dose assessment study. AB - The clinical diagnosis of idiopathic Parkinson's disease (IPD) remains difficult and is supported by a favorable response to levodopa, while failure to respond represents an exclusion criterion. Recently, the response to subcutaneous apomorphine has been suggested as a tool in predicting levodopa responsiveness in parkinsonian syndromes. We administered apomorphine at doses of 10, 50, and 100 micrograms/kg subcutaneously against placebo over two consecutive days in 37 patients with parkinsonism and evaluated the motor response for 90 min after each dose. Subsequently, we compared the motor response with the follow-up response to levodopa therapy and to a final diagnosis. Twenty-seven patients of 37 showed a positive response to apomorphine, and 10 had a negative response. All positive responses to the apomorphine test were obtained with 50 or 100 micrograms/kg doses. Because of the high frequency of side effects with the dose of 100 micrograms/kg, 50 micrograms/kg seems more useful. After an adequate period of levodopa/carbidopa therapy (12-month follow-up), 29 patients improved; 25 of these had demonstrated a positive response to the apomorphine test. The final diagnosis of IPD, made on the basis of an exhaustive clinical and neuroradiological evaluation and on the response to chronic levodopa therapy, was in good agreement with the response to the apomorphine test (predictivity of diagnosis, 86.4%). Our data indicate that subcutaneous apomorphine at the dose of 50 micrograms/kg is a useful tool in the differential diagnosis of parkinsonian syndromes. PMID- 8474483 TI - Subcutaneous apomorphine in Parkinson's disease: response to chronic administration for up to five years. AB - Subcutaneous apomorphine, administered by continuous waking-day infusion with boluses, or by repeated intermittent injection, was given to 71 parkinsonian patients with severe refractory levodopa related on-off fluctuations for 1-5 years. A mean reduction in daily off period time of approximately 50% was maintained, and the incidence of neuropsychiatric toxicity remained low on long term follow-up. No clinically significant tolerance or loss of therapeutic effect was seen, although increasingly severe on-phase dyskinesias and postural instability marred the long-term therapeutic response in many patients. Despite these drawbacks, apomorphine, when combined with the peripheral dopamine receptor agonist domperidone, represents a significant therapeutic advance in the management of late-stage Parkinson's disease and should certainly be considered before experimental implantation procedures. PMID- 8474484 TI - Nocturnal akathisia in Parkinson's disease: treatment with clozapine. AB - We present the results obtained using low doses of clozapine (mean dose 26.4 mg at bedtime) in the treatment of nocturnal akathisia in nine patients with Parkinson's disease for a mean period of 12.5 months. The results were excellent in all the patients. Furthermore, three patients experienced a remarkable improvement in rest tremor and in five patients the confusional state that accompanied the akathisia also disappeared. No serious side-effects were observed. We believe that clozapine is a very useful drug for the relief of nocturnal akathisia in parkinsonian subjects. PMID- 8474485 TI - Cocaine-related movement disorders. AB - We describe four patients, two with Tourette's syndrome, one with the combination of idiopathic dystonia and essential-like tremor, and one with tardive dystonia, who noted marked exacerbation of their movement disorders after exposure to cocaine. These patients provide support for the hypothesis that dopaminergic preponderance plays an important role in the pathogenesis of certain hyperkinetic movement disorders. Cocaine should be regarded as an important cause or precipitant of hyperkinetic movement disorders. PMID- 8474486 TI - Tremor due to stroke. AB - We report on four patients with unilateral tremor stemming from cerebrovascular accidents. In two patients with proven lesions of the thalamus, the tremor was irregular and, in addition, there was dystonic posturing of the affected arm. Tremor and dystonic posturing had appeared after the stroke. In the other two patients tremor had occurred immediately at the onset of the stroke and lasted only a few days. The tremors were of small amplitude and high frequency, and lesions could not be found on CT or MRI in these two patients. None of our patients showed signs of the so-called rubral tremor. PMID- 8474487 TI - Assessment of adaptive functioning in Huntington's disease. AB - The Huntington's Disease Activities of Daily Living (HD-ADL) scale is a 17-item informant-completed instrument for rating adaptive functioning in Huntington's disease (HD) patients. To assess the reliability and clinical correlates of the HD-ADL, it was administered along with the Mini-Mental State Exam (MMSE) and Quantified Neurological Exam (QNE) to 93 HD patients. The HD-ADL has high internal consistency (coefficient alpha = 0.91). Principal components factor analysis of the HD-ADL revealed four factors (General Functioning, Domestic Activities, Home Upkeep, and Family Relationships) accounting for 72% of the total variance. MMSE score, motor impairment score, and duration of disease were the best predictors of HD-ADL score. Similar results were obtained in an independent replication sample of patients. The HD-ADL scores correlate with Shoulson and Fahn's total functional capacity (TFC) index (r = -0.89). The HD-ADL scale is a reliable and valid instrument for assessing adaptive function in HD patients. PMID- 8474488 TI - Benign neonatal sleep myoclonus: clinical features and video-polygraphic recordings. AB - Benign neonatal sleep myoclonus is a syndrome characterized by the occurrence of repetitive myoclonic jerks of the extremities exclusively during non-rapid eye movement sleep in the early life of healthy newborns. No etiological factors are present. The onset is within the first 15 days of life with spontaneous disappearance within 3-4 months. These myoclonic events are commonly diagnosed as epileptic seizures. We observed 12 newborns with this clinical pattern; the follow-up ranges from 12 to 60 months. Long-term videopolygraphic electroencephalographic (EEG) monitoring demonstrated normal EEG activity, thus confirming that these unusual events were nonepileptic. PMID- 8474489 TI - Reflex blepharospasm associated with bilateral basal ganglia lesion. AB - A patient with a bilateral striatal lesion secondary to anoxia presented reflex blepharospasm associated with parkinsonism and dystonia in the limbs. The blink reflex excitability curve was enhanced and the R-2 response prolonged as in patients with essential blepharospasm. The findings in this patient support the notion that blepharospasm may be secondary to basal ganglia dysfunction through abnormal facilitation of reticular formation neurons controlling facial nucleus motoneuron excitability. PMID- 8474490 TI - Adult onset myoclonic Huntington's disease. AB - A patient with adult onset Huntington's disease (HD) and prominent action myoclonus is described. Neither epileptiform activity nor electroencephalography (EEG) correlates of the movements was found. Unlike the case with most (nonmyoclonic) HD patients, centro-parietal components of somatosensory evoked potentials (SEPs) were well defined and a clear V2 response was found. Treatment with valproic acid greatly reduced myoclonus suggesting that the gamma aminobutyric acid (GABA) system might be involved in the pathophysiology of myoclonus in HD. PMID- 8474491 TI - A case of posttraumatic tremor treated by chronic stimulation of the thalamus. PMID- 8474492 TI - MR imaging findings of tremors associated with lesions in cerebellar outflow tracts: report of two cases. AB - Two cases with severe tremors were studied by means of electromyograms using surface electrodes and also by magnetic resonance (MR) imaging. The first case was associated with multiple sclerosis and demonstrated a severe postural cerebellar tremor and an alternate activation of antagonist muscles in the right arm. The second case, with hemorrhage in the brainstem, demonstrated a severe tremor at rest and mixed synchronous and alternating activation of antagonist muscles in the left forearm. MR imaging studies localized lesions possibly responsible for these tremors. In the first case a lesion was located in the superior cerebellar peduncle just under the decussation, and in the second case a lesion was found between the red nucleus and the thalamus, with possible involvement of both the cerebellothalamic and nigrostriatal pathways. The first case accords with the theory that a lesion located in the dentate nucleus and its projection can cause severe postural cerebellar tremor. The lesion demonstrated in the second case may be responsible for "cerebellar tremor at rest" or "static (resting) cerebellar tremor." PMID- 8474493 TI - Basal ganglia infarction as a possible cause of cervical dystonia. AB - Cervical dystonia (CD) is usually an idiopathic disorder that results in abnormal movements and painful postures of the neck. Although symptomatic CD caused by focal CNS lesions has been described in the literature, it is an exceedingly rare phenomenon. We report two women who had an abrupt onset of CD at the ages of 39 and 68 years. Each patient had rotation of the head to the right and was found to have a lacunar infarction in the left putamen on magnetic resonance imaging scan. The abrupt onset of symptoms and appropriate location and laterality of the cerebral lesions suggest an etiologic link between the infarctions and the patients' CD. These cases are the first reports of CD possibly caused by basal ganglia infarction. PMID- 8474494 TI - Postneuroleptic laryngeal dyskinesias: a cause of upper airway obstructive syndrome improved by local injections of botulinum toxin. AB - We report a case of laryngeal dyskinesia resulting in severe rest and exercise dyspnea. A 51-year-old man treated for 2 years with flupentixol, an incisive neuroleptic, developed severe dyspnea due to intermittent, rhythmic, and dystonic movements of the vocal cords and upper airway. Local injections of botulinum toxin resulted in spectacular regression of laryngeal spasms and major improvement in breathing. This case emphasizes the risk of upper respiratory dyskinesias associated with neuroleptic treatment and shows the feasibility of a new local treatment in this life-threatening disorder. PMID- 8474495 TI - Familial idiopathic strio-pallido-dentate calcifications with late onset extrapyramidal syndrome. AB - A family with autosomal dominant inheritance of idiopathic strio-pallidodentate calcifications and late onset of extrapyramidal symptoms is reported. Clinical features consisted of parkinsonism in one member and postural tremor in two. Depression and dysarthria were present in all cases. All symptomatic members showed a peculiar biochemical abnormality consisting of reduced 25-OH vitamin D3 with normal levels of 1,25(OH)2 vitamin D3, suggesting an inborn error of Vitamin D metabolism. The biochemical, clinical, and genetic pattern of this family distinguishes this syndrome from the larger group of secondary familial basal ganglia calcifications. PMID- 8474496 TI - Ataxia without telangiectasia. AB - Ataxia telangiectasia (AT) is an autosomal recessive hereditary disorder characterized by onset in infancy or childhood of a cerebellar and later extrapyramidal disorder associated with telangiectasias and an immune deficit. Only a handful of cases have been described in which the features were not stereotypic. This report describes a case that is classic except for the absence of telangiectasias through age 17. This and other cases suggest that a new, more inclusive term be used to describe the syndrome of ataxia with immune deficit until the genetic abnormalities in these disorders become identifiable. PMID- 8474497 TI - Function of dopamine receptors in young-onset Parkinson's disease: prolactin response. AB - The basal levels of prolactin (PRL) and their changes after i.v. thyrotropin releasing hormone (TRH) administration after bromocriptine (BCT) pretreatment (BCT/TRH test) were monitored in 12 patients with young-onset Parkinson's disease (PD) (before 40 years of age) and 10 patients with older-onset PD (after 40 years of age), as well as in two groups of healthy subjects (10 persons in each), age matched with older-onset (control A) and young-onset (control B) parkinsonians. The basal PRL levels were normal in both groups of patients. When given after BCT, TRH induced a significantly lower PRL increase in older-onset parkinsonians than in controls. This response was even more blunted in young-onset patients, being significantly more attenuated than in older-onset PD patients. PMID- 8474498 TI - Stereotyped hand clasping: an unusual tardive movement disorder. AB - We report an 83-year-old woman with vascular parkinsonism who presented with stereotyped rhythmical hand-clasping movements after 18 months exposure to neuroleptics. Although stereotypical rhythmical orolinguomasticatory and limb movements are the most common tardive dyskinesia in the elderly, we feel this woman's hand clasping represents another unusual expression of a tardive movement disorder. PMID- 8474499 TI - Myoclonus and tremor induced acutely by administration of tumor necrosis factor in a patient with Ehlers-Danlos syndrome. PMID- 8474500 TI - Spasmodic torticollis in multiple sclerosis: significance of an upper cervical spinal cord lesion. PMID- 8474501 TI - Effect of L-dopa on oculogyric crises in a case of dopa-responsive dystonia. PMID- 8474502 TI - Acute and long-term response to apomorphine in cranial dystonia. PMID- 8474503 TI - Unilateral blepharospasm stemming from a thalamomesencephalic lesion. PMID- 8474504 TI - Acetazolamide therapy of menstrual-related fluctuations in Parkinson's disease. PMID- 8474505 TI - Paroxysmal stimulus-sensitive spasmodic torticollis. PMID- 8474506 TI - Hemiplegic dystonia associated with regional cortical dysplasia (pachygyria). PMID- 8474507 TI - A patient with a resting tremor and a lacunar infarction at the border between the thalamus and the internal capsule. PMID- 8474508 TI - Persistent parkinsonism and tardive dyskinesia induced by clebopride. PMID- 8474509 TI - Unilateral pallidal lesion after acute disulfiram intoxication: a clinical and magnetic resonance study. PMID- 8474510 TI - Cessation of writer's cramp after stroke. PMID- 8474511 TI - Baltic myoclonus and Crohn's disease. PMID- 8474512 TI - The development of sex typing in middle childhood. AB - The present study examined the development of sex typing during middle childhood, using a sample of 558 children aged 5-12 years. The purpose of the study was to provide information about the developmental course and stability of various aspects of sex typing during this period and to examine the relative contributions of cognitive and environmental factors to sex-role development. Multiple measures of sex typing were obtained, including indices of personal preference, knowledge of stereotypes, and flexibility in the domains of activities, occupations, and traits. We also collected information about the child's cognitive maturity, exposure to sex-typed models at home, and socioeconomic status. Results supported the need for an integrative theory of sex role development, incorporating factors emphasized by cognitive-developmental, schematic-processing, and social learning theories. Knowledge of stereotypes, flexibility, and sex-typed personal preferences all increased with age during middle childhood. There were also individual differences in sex typing that were stable over a 1-year period. Distinct "cognitive" and "affective" aspects of sex typing were identified using a principal components analysis. Cognitive elements (flexibility and knowledge of stereotypes) were largely a function of the child's cognitive maturity level, although social-environmental factors such as father's presence in the home also had some effect. Affective elements (sex-typed preferences for activities, occupations, and peers), on the other hand, were related more consistently to sex typing of the home environment. Children whose mothers frequently modeled "reversed" sex-role behaviors (i.e., traditionally "masculine" household and child-care tasks) were less sex typed in their own preferences. However, cognitive factors were also important, in that children who believed gender stereotypes to be flexible were less sex typed in their choices of activities, occupations, and peers. In sum, both cognitive maturation and socialization experiences contribute to the development of sex typing during middle childhood. Potential practical implications of these findings, as well as implications for stereotyping in other social domains such as race and ethnicity, are discussed. PMID- 8474513 TI - Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. AB - BACKGROUND: Although tests for occult blood in the feces are widely used to screen for colorectal cancers, there is no conclusive evidence that they reduce mortality from this cause. We evaluated a fecal occult-blood test in a randomized trial and documented its effectiveness. METHODS: We randomly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year, to screening every two years, or to a control group. Participants who were screened submitted six guaiac-impregnated paper slides with two smears from each of three consecutive stools. About 83 percent of the slides were rehydrated. Participants who tested positive underwent a diagnostic evaluation that included colonoscopy. Vital status was ascertained for all study participants during 13 years of follow-up. A committee determined causes of death. A single pathologist determined the stage of each tissue specimen. Differences in mortality from colorectal cancer, the primary study end point, were monitored with the sequential log-rank statistic. RESULTS: The 13-year cumulative mortality per 1000 from colorectal cancer was 5.88 in the annually screened group (95 percent confidence interval, 4.61 to 7.15), 8.33 in the biennially screened group (95 percent confidence interval, 6.82 to 9.84), and 8.83 in the control group (95 percent confidence interval, 7.26 to 10.40). The rate in the annually screened group, but not in the biennially screened group, was significantly lower than that in the control group. Reduced mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer. CONCLUSIONS: Annual fecal occult-blood testing with rehydration of the samples decreased the 13-year cumulative mortality from colorectal cancer by 33 percent. PMID- 8474514 TI - Out-of-hospital transcutaneous pacing by emergency medical technicians in patients with asystolic cardiac arrest. AB - BACKGROUND: Transcutaneous cardiac pacemakers generate electrical stimuli that pace the heart through external electrodes that adhere to the chest wall. Transcutaneous pacing has been useful in some patients with bradycardia, but its efficacy in patients with asystole and full cardiac arrest has been limited, possibly because of delays in the initiation of pacing. We studied the efficacy of early transcutaneous pacing in patients with out-of-hospital asystolic cardiac arrest. METHODS: For three years we provided transcutaneous pacemakers to about half the fire districts in a large emergency-medical-services system (the intervention group). In these districts, we authorized emergency medical technicians (EMTs) to begin transcutaneous pacing in patients with cardiac arrest and primary asystole or post-defibrillation asystole. Pacing was done as early as possible, before endotracheal intubation or intravenous medication. EMTs in the other fire districts (the control group) treated similar patients with basic cardiopulmonary resuscitation but without transcutaneous pacing. RESULTS: The EMTs in the intervention group initiated transcutaneous pacing in 112 of the 278 patients with primary asystole. Of these patients, 22 (8 percent) were admitted to the hospital, and 11 (4 percent) were discharged. Among the 259 patients treated by the EMTs in the control group, 21 (8 percent) were admitted to the hospital, and 5 (2 percent) were discharged. The two groups did not differ significantly with respect to the rate of hospital admission or survival. Survival after early pacing for post-defibrillation asystole was no better than survival after pacing for primary asystole. CONCLUSIONS: Transcutaneous pacing appears to offer no benefit in patients with asystolic cardiac arrest, even when it is performed as early as possible by EMTs in the field. Our data suggest that the widespread implementation of early transcutaneous pacing for out-of-hospital asystolic cardiac arrest would be ineffective. PMID- 8474515 TI - Recent advances in pulmonary medicine (1). PMID- 8474516 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 19-1993. A 39-year-old man with bilateral renal masses a few months after treatment for Hodgkin's disease, stage IIA. PMID- 8474517 TI - Colorectal cancer screening comes of age. PMID- 8474518 TI - Antimicrobial prophylaxis after tick bites. PMID- 8474519 TI - Antimicrobial prophylaxis after tick bites. PMID- 8474520 TI - Antimicrobial prophylaxis after tick bites. PMID- 8474521 TI - Childhood immunizations. PMID- 8474522 TI - Childhood immunizations. PMID- 8474523 TI - Childhood immunizations. PMID- 8474524 TI - Noninvasive prediction of pulmonary-capillary wedge pressure. PMID- 8474525 TI - Noninvasive prediction of pulmonary-capillary wedge pressure. PMID- 8474526 TI - Bronchial hyperresponsiveness in heart failure. PMID- 8474527 TI - Novel gifts from pharmaceutical companies. PMID- 8474528 TI - Retained needle fragments and digital dissection. PMID- 8474529 TI - Ultrastructural study of Cryptococcus neoformans by quick-freezing and deep etching method. AB - The three-dimensional ultrastructure of Cryptococcus neoformans was studied by quick-freezing and deep-etching (QF-DE) method. C. neoformans, strain CDC551, was cultured on agar. The viable yeast cells (10(7) cells) were inoculated into each mouse from the tail vein. Three weeks after the inoculation, the brains of the mice were perfused with fixatives, quickly frozen, freeze-fractured, deeply etched and rotary shadowed with platinum and carbon. In addition, the viable cells of C. neoformans on agar were picked up and quickly frozen, and replica membranes were prepared as described above. The ultrastructure of C. neoformans was three-dimensionally demonstrated by the QF-DE method. The capsule was composed of fine meshworks of microfibrils (10-13 nm in diameter), which were directly attached to the cell walls. The capsule of the in vivo yeasts (yeast cells in the brain lesion) was thicker than that of the in vitro yeasts (yeast cells on agar culture). At the outer part of the cell wall, a particle accumulating layer was observed. This layer in vivo was thicker than that in vitro. Occasionally, the yeast cells were ingested by phagocytes in the mouse brain. Although the cytoplasm of such yeast cells was destroyed, the capsular meshworks were well preserved. The ultrastructure of the capsule was the same both in cultured and phagocytized yeasts in the cystic lesions of the brains. This lack of morphological changes of the capsular meshworks suggests that they are resistant to the digestion by phagocytes. This stability of capsular structures may provide one of the important pathogenic factors in cystic lesions by C. neoformans. PMID- 8474530 TI - Two bacteria causing farmer's lung: fine structure of Thermoactinomyces vulgaris and Saccharopolyspora rectivirgula. AB - The fine structure of Thermoactinomyces vulgaris and Saccharopolyspora rectivirgula is described by transmission electron microscopy. These two bacteria are the most common microbes causing farmer's lung. The fine structure of hyphae, germination of endospores and the details of conidial wall layers of T. vulgaris, as well as the fine structure of septate hypha and globose, polygonal conidia of S. rectivirgula are described. The conidial wall of T. vulgaris consisted of an inner multilayered spore coat, intermediate spore coat and outer spore coat. The findings are important for the investigations to find fragments of these bacteria in the lungs of exposed patients and experimental animals. PMID- 8474531 TI - Dialysable leukocyte extracts modify the course of experimental paracoccidioidomycosis in the Syrian hamster. AB - The effect of dialysable leukocyte extracts (DLE) obtained from hamsters immunized with Paracoccidioides brasiliensis (immune DLE) and from non-immunized hamsters (non-immune DLE) was studied in hamsters inoculated with P. brasiliensis by the intratesticular route. Treatment with immune or non-immune DLE was started during the third week of infection and was repeated at 7, 11, 15 and 19 weeks. A group of untreated infected animals was used as control. Animals were submitted to the delayed hypersensitivity skin test to P. brasiliensis antigen (PbAg) in vivo and assayed in vitro by the macrophage migration inhibition test in the presence of Phytohemagglutinin (PHA) and PbAg and by immunodiffusion for specific antibody. The animals were sacrificed at 4, 8, 12, 16 and 20 weeks. The morphology and extension of the lesions were studied at the inoculation site, and in lymph nodes, lungs, liver, spleen and kidneys. In contrast to the controls, animals treated with both DLEs maintained a positive cell-mediated immune response throughout the experiment and developed less extensive infection with a significantly lower number of fungi in the lesions. The results suggest that immune and non-immune DLE preparations modified the evolution of experimental paracoccidioidomycosis with equal efficiency. This similarity may be explained by the immunoregulatory activities of both extracts. PMID- 8474532 TI - Characterization of functional responses in A9 cells transfected with cloned rat 5-HT1C receptors. AB - Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp and calcium recording techniques. Stimulation of 5-HT1C receptors evoked outward currents clamped at -50 mV. The outward currents were reduced when GTP was excluded from the intracellular recording solution or when GDP-beta-S was added. 8-Bromo cyclic AMP (5 mmol/l) neither produced an effect per se nor affected the 5-HT-induced outward current in A9 cells, thus excluding cAMP as a second messenger involved in 5-HT1C receptor activation. Phorbol myristic acetate (PMA; 10 mumol/l) did not affect the electrical activity of the transfected A9 cells but reduced the 5-HT-induced current amplitude to 71 +/- 9% of the control value (n = 12). This indicates that activation of protein kinase C does not play a direct role in the 5-HT-induced response in these cells. The 5-HT induced currents mainly involved potassium ions, although a small contribution of chloride ions was also observed. The 5-HT induced current was inhibited by the K+ channel blocking agents tetraethylammonium (1 mmol/l), apamin (0,5 mumol/l) and 4-aminopyridine (5 mmol/l). The 5-HT-induced currents recorded at -50 mV were unaffected by removal of extracellular calcium, but inclusion of the calcium chelator BAPTA (5 mmol/l) in the intracellular solutions abolished the current. Measurement with the calcium indicator Fluo-3 revealed a 5-HT-induced increase in intracellular calcium which was not affected by removal of extracellular calcium but declined after repeated stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474533 TI - Heterogeneity of 5-HT receptor subtypes in isolated human femoral and saphenous veins. AB - Changes in tension were monitored isometrically on helical strips from both femoral and saphenous human veins obtained during autopsy and during surgical removal of varicose veins respectively. Both venous tissues contracted in response to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and 8 hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). While 5-HT was about 2 times more potent in saphenous (pD2 = 7.35) than in femoral veins (pD2 = 7.04), 5-CT stimulated the saphenous vein (pD2 = 7.62) at about 20 times lower concentrations than were required for stimulation of the femoral vein (pD2 = 6.27). 8-OH-DPAT induced venoconstriction only when used at very high concentrations and pD2 values could not be determined. These data suggested different subtypes and/or distribution of 5-HT receptors in both venous preparations. Further evidence for this was obtained by the observation that spiperone (a 5-HT receptor blocker with high affinity for 5-HT2 and 5-HT1A sites) produced a parallel shift to the right of the 5-HT curve in femoral veins but elicited a biphasic displacement of the 5 HT curve in saphenous veins. In the femoral vein, spiperone showed a pA2 value of 9.20 +/- 0.08, statistically not different from that calculated for the spiperone sensitive 5-HT effect in saphenous vein (pA2 = 9.14 +/- 0.08). The results suggest that regional variations in the distribution of 5-HT receptor subtypes do exist, human femoral veins possessing mainly 5-HT2 receptors whereas in human saphenous veins both 5-HT1-like and 5-HT2 receptors are present. PMID- 8474534 TI - Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine. AB - The effects of agonists and antagonists of 5-hydroxytryptamine (5-HT) receptors on the release of endogenous 5-HT from enterochromaffin cells were studied in the vascularly perfused isolated guinea-pig small intestine. The experiments were done in the presence of tetrodotoxin in order to exclude a neuronally mediated influence on 5-HT release. The 5-HT3 receptor agonist 2-methyl-5-HT increased 5 HT release, and this effect was antagonized by 1 nmol/l tropisetron. Nanomolar concentrations of tropisetron, MDL 72,222 and granisetron decreased 5-HT release. Ondansetron (0.1 and 1 mumol/l) did not modify 5-HT release. 5-Methoxytryptamine, BIMU8 and cisapride concentration-dependently inhibited 5-HT release. BIMU8 was more potent than 5-methoxytryptamine. Micromolar concentrations of tropisetron (1 and 10 mumol/l) enhanced the release, whilst methiothepine (0.1 mumol/l) did not affect the release of 5-HT. The results suggest that enterochromaffin cells of the guinea-pig ileum do not contain 5-HT1 and 5-HT2 receptors, but are endowed with 5-HT3 and 5-HT4 autoreceptors. Activation of the 5-HT3 receptors triggers a positive feedback mechanism leading to an increase of 5-HT release. The 5-HT3 receptors on the enterochromaffin cell differ from neuronal 5-HT3 receptors on guinea-pig myenteric plexus by their high affinity for tropisetron and MDL 72,222, and their very low affinity for ondansetron. Stimulation of 5-HT4 receptors causes inhibition of release; the inhibitory 5-HT4 receptor mechanism appears to predominate. PMID- 8474535 TI - Different effects of 1-methyl-4-phenyl-pyridinium (MPP+) on monoamine oxidase of dopaminergic terminals in caudate nucleus slices from pigmented and from albino rabbits. AB - Slices of caudate nucleus from pigmented and from albino rabbits were preincubated in vitro for 24 h with different concentrations of the neurotoxic compound MPP+. Subsequently, endogenous dopamine (DA) in the slices was determined by HPLC. MPP+ (1 and 3.2 mumol/l) was more effective in diminishing DA levels in caudate nucleus slices from albino than in slices from pigmented rabbits. Following 24 h pretreatment with MPP+, the accumulation of [3H]-DA in caudate nucleus slices from pigmented rabbits was either enhanced (at 0.32 mumol/l, 1 mumol/l and 3.2 mumol/l MPP+) or reduced (at 32 mumol/l MPP+). In contrast, MPP+ did not enhance the accumulation of [3H]-DA in caudate nucleus tissue from albino rabbits and was more potent in reducing the [3H]-DA content in slices from albino than in slices from pigmented rabbits. When the selective type A monoamine oxidase (MAO) inhibitor clorgyline was present during pre-incubation, but not when the selective type B MAO inhibitor deprenyl was, the concentration response curve for MPP+ with caudate nucleus slices from pigmented rabbits was similar to that obtained with slices from albino rabbits. Clorgyline and deprenyl did not change the effects of MPP+ in caudate nucleus slices from albino rabbits. These findings are compatible with the hypothesis that the MAO within dopaminergic terminals in the caudate nucleus of pigmented, but not of albino, rabbits is of type A since MAO-A is preferentially inhibited by MPP+. In line with this hypothesis, the accumulation of the preferential MAO-A substrate [3H]-5 HT in caudate nucleus slices from pigmented rabbits was about 39% lower than that in slices from albino rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474536 TI - The part played by catechol-O-methyltransferase in the plasma kinetics of 3,4 dihydroxyphenylglycol and 3,4-dihydroxyphenylalanine in the anaesthetized rabbit. AB - The present study, carried out in anaesthetized rabbits, aimed at determining the effects of catechol-O-methytransferase (COMT) inhibition on the plasma kinetics of infused 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxyphenylalanine (DOPA) as well as on endogenous plasma noradrenaline, DOPEG, DOPA and 3-methoxy-4 hydroxyphenylglycol (MOPEG). The plasma kinetics of infused MOPEG were also evaluated. To block the function of COMT, 3,4-dihydroxy-4'-methyl-5 nitrobenzophenone (Ro 40-7592) was given intravenously. Dose-finding experiments, in which the drug-induced fall in endogenous plasma MOPEG was used to quantify COMT inhibition, indicated that a Ro 40-7592 dose of 3 mg/kg followed by 1.5 mg/kg every 30 min was sufficient to obtain a virtually complete inhibition of COMT. More than 150 min of COMT inhibition were required for endogenous MOPEG to disappear from plasma, since the plasma half-life of MOPEG was 54 min. COMT inhibition produced marked increases in the plasma levels of endogenous DOPA (1.7 fold) and DOPEG (3.9-fold) and did not alter endogenous plasma noradrenaline. The results concerning the effect of COMT inhibition on the plasma kinetics of infused DOPA and DOPEG were as follows: the plasma clearance of DOPA was not altered, whereas that of DOPEG fell by 41%; the plasma half-life of DOPA increased from 4.9 to 13.0 min and that of DOPEG from 4.8 to 31.0 min; there was an increase in the volume of distribution of DOPA (2 to 3-fold) and DOPEG (4 to 5 fold).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474537 TI - Effects of catechol-O-methyltransferase inhibition on the plasma clearance of noradrenaline and the formation of 3,4-dihydroxyphenylglycol in the rabbit. AB - The purpose of this study was to elucidate the finding of Friedgen et al. (1993 b) that catechol-O-methyltransferase (COMT) inhibition is much more effective in increasing the plasma concentration of endogenous dihydroxyphenylglycol (DOPEG) than in increasing the plasma concentration of infused DOPEG. To this end, reserpine-pretreated rabbits were anaesthetized and infused with noradrenaline and/or DOPEG, and the plasma clearances of infused noradrenaline (ClNA) and DOPEG (ClDOPEG) as well as the plasma DOPEG response to noradrenaline infusion [as reflected by the ratio of the steady-state increase in plasma DOPEG (delta DOPEG) to that in plasma noradrenaline (delta NA)] were determined before and after blockade of neuronal uptake by desipramine. Experiments were carried out either under control conditions or after COMT inhibition by i.v. administration of 3,4 dihydroxy-4'-methyl-5-nitrobenzophenone (Ro 40-7592). On the assumption that rates of neuronal noradrenaline uptake equal steady-state rates of neuronal DOPEG formation, the desipramine-sensitive components of ClNA and delta DOPEG/delta NA were used to estimate the apparent plasma clearance of DOPEG formed intraneuronally (Clf-DOPEG) in response to noradrenaline infusion. ClNA was 83.6 ml kg-1 min-1 in the absence and 48.1 ml kg-1 min-1 in the presence of desipramine. Neither the former nor the latter value was altered after COMT inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474538 TI - Release and disposition of 3H-noradrenaline in the saphenous vein of neonate and adult dogs. AB - Release of 3H-noradrenaline and formation of 3H-metabolites were studied in the saphenous vein of newborn (mean age, 18 h) and adult dogs. Vein strips were incubated with 0.23 mumol/l of 3H-noradrenaline during 1 h and washed out for 110 min; thereafter, the perifusion fluid was collected in 5-min samples. Electrical stimulation was applied at 120 min (1 Hz, 2 ms, 100 V, for 5 min). In some experiments the tissues were preincubated with 1 mmol/l pargyline (to inhibit monoamine oxidase). In these experiments, 12 mumol/l cocaine (to inhibit uptake1), 41 mumol/l hydrocortisone (to reduce uptake2) and 50 mumol/l U-0521 (to inhibit COMT) were present during the perifusion. 3H-noradrenaline, 3H-DOPEG, 3H NMN, 3H-DOMA and 3H-OMDA were separated by column chromatography. The noradrenaline content of the tissue was estimated by HPLC followed by electrochemical detection. A morphological study was also carried out by light and electron microscopy. The endogenous noradrenaline content of the saphenous vein was 4.3 times higher in adults than in neonates. The number of varicosities was similar in adults and newborns but the number of vesicles per varicosity profile was 5 times higher in adults. Hence, the endogenous noradrenaline content per vesicle was about the same in adults and newborns. The accumulation of 3H noradrenaline per vesicle was about 5 times higher in newborns than in adults. On the other hand, the vein wall media of neonates was about 3 times thinner than that of adults. The evoked fractional release of tritium was about 10 times higher in neonates than in adults, whether the inactivation pathways were blocked or not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474539 TI - Characterization of the angiotensin II-receptor subtype in the longitudinal smooth muscle of the rat portal vein. AB - The purpose of the present study was to identify the angiotensin II-receptor subtype involved in the enhancement of the amplitude of the phasic contractions by angiotensin II in the isolated rat portal vein preparation. At an extracellular Ca2+ concentration of 0.9 mmol/l and a K+ concentration of 4 mmol/l, angiotensin II induced concentration-dependent increases in the amplitude of the phasic contractions. The enhancement of phasic contraction amplitude caused by angiotensin II was not significantly altered by pretreatment of the rat portal vein with indomethacin 10(-5) mol/l or nitro-L-arginine 10(-4) mol/l, indicating that neither prostaglandins nor the endothelium derived-relaxing factor (NO) are involved. Losartan (DuP 753), a nonpeptide selective AT1-receptor antagonist, concentration-dependently shifted the concentration-response curve for the effect of angiotensin II on the amplitude of the contractions to the right, without reducing the maximal response (pA2 = 8.6, slope = 0.98), thus suggesting competitive antagonism at the level of AT1-receptors. By contrast, PD 123,177, a nonpeptide selective AT2-receptor antagonist, even at 10(-5) mol/l, caused no significant change of the phasic myogenic response to angiotensin II, indicating the absence of AT2-receptor involvement. Dithiothreitol, a disulfide reducing agent which is known to inactivate AT1-receptors in various tissues, markedly inhibited (3 mmol/l) or even abolished (5 mmol/l) the contractile response of the rat portal vein to angiotensin II, supporting the conclusion that these receptors can be classified as AT1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474541 TI - [A hide-and-seek kind of disorder]. PMID- 8474540 TI - N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis, decreases noradrenaline outflow in rat isolated perfused mesenteric vasculature. AB - In the isolated perfused rat mesenteric vasculature with intestine attached N omega-nitro-L-arginine (L-NNA) (30 mumol/l), an inhibitor of nitric oxide (NO) synthesis from L-arginine, did not alter spontaneous noradrenaline outflow. Transmural field stimulation (2-10 Hz) caused a frequency-dependent increase in noradrenaline outflow. The evoked overflow was reduced by L-NNA. L-Arginine (0.3 mmol/l) attenuated the inhibition of noradrenaline overflow by L-NNA. These results suggest that NO increases the release of noradrenaline in rat mesenteric vasculature. PMID- 8474542 TI - [Treatment with estrogens and the risk of gallstone formation]. PMID- 8474543 TI - [Should the testing policy for the prevention of HIV infections in patients and in health care personnel be changed?]. PMID- 8474544 TI - [AIDS and HIV infection as occupational disease]. PMID- 8474545 TI - [Iatrogenic HIV infection]. PMID- 8474546 TI - [Chronic functional constipation in children]. PMID- 8474547 TI - [The consent discussion for organ donation]. PMID- 8474548 TI - [Constipation in childhood; evaluation of a diagnostic-therapeutic protocol]. AB - In 87 children with constipation an assessment was made of the causes, and of the effect of treatment. Two subdivisions were made, one by age (< 3 years and > or = 3 years) and the second into 'own' or 'referred' patients. For the 59 own children a diagnostic-therapeutic protocol was used, the three-phase protocol. For children over 3 years (n = 29) this policy consists in the first phase of anamnesis, physical examination, diet and oral and/or rectal laxatives. In the second phase, toilet training is administered in combination with diet and oral laxatives. The third phase comprises continuation of the diet and tapering off of the laxatives. If no improvement is seen, supplementary examination is carried out. In the group of own patients younger than 3 years, supplementary examination is already carried out during the first phase. Functional constipation was diagnosed in 69% and 98%, respectively, of the 36 patients under 3 years and the 51 over 3 years. Hirschsprung's disease was diagnosed in 14% and 2%, respectively. In the children > or = 3 years with functional constipation the three-phase policy was successful in 86% with a mean duration of the treatment of 9.5 months. The efficiency of diagnostic examination of children over 3 years appears to be low, justifying the proposed three-phase policy. In children under 3 years, on the other hand, limited laboratory examination is necessary during the first phase. Examination for the presence of Hirschsprung's disease, by means of rectal biopsy or anorectal manometry is indicated if the treatment during the first phase is unsuccessful. PMID- 8474549 TI - [Chronic constipation in children; good results of biofeedback training as supplementary therapy]. AB - In two children with refractory constipation biofeedback training was successfully used as a supplementary therapy. In this treatment, a balloon tied to the end of the catheter is inserted into the rectum and inflated with ever decreasing amounts of air, so as to increase rectal sensibility. In addition, the defaecation pattern is displayed on a monitor. The child learns to control contraction and relaxation of the musculature involved in defaecation. PMID- 8474550 TI - [Controversies in preventive health care. II. Preconception and prenatal care]. PMID- 8474551 TI - [The prevention of recurrent erysipelas]. PMID- 8474552 TI - [Benefit of antibiotics in acute sore throat]. PMID- 8474553 TI - [Wrong questions, erroneous answers; an absurd choice]. PMID- 8474554 TI - Age- and seizure-related changes in noradrenaline and dopamine in several brain regions of epileptic El mice. AB - Noradrenaline (NA) and dopamine (DA) levels in six brain regions of stimulated and nonstimulated El (El[s] and El[ns]) mice and their maternal ddY mice were determined at various ages and various times after a convulsion. The NA levels in the striatum and hippocampus of 12-week-old El[s] and El[ns] mice were lower than in ddY mice, and remained lower in 23-week-old El[s] mice, but not in El[ns] mice. DA levels were lower in the striatum of El[s] mice than in El[ns] and ddY mice at 16 and 23 weeks of age. NA levels decreased during seizure in the striatum and hippocampus of El[s] mice, and returned to preconvulsive levels 1 hr after convulsion in the striatum and 30 min in the hippocampus. DA levels in the striatum of El[s] mice decreased during convulsion and increased from 1 to 10 min after convulsion. These changes suggest that the NAergic systems in the striatum and hippocampus and the DAergic system in the striatum have important roles in relation to seizure susceptibility in El mice. PMID- 8474555 TI - The two catalytic components of the 2-oxoglutarate dehydrogenase complex in rat cerebral synaptic and nonsynaptic mitochondria: comparison of the response to in vitro treatment with ammonia, hyperammonemia, and hepatic encephalopathy. AB - The effects of in vitro treatment with ammonium chloride, hepatic encephalopathy (HE) due to thioacetamide (TAA) induced liver failure and chronic hyperammonemia produced by i.p. administration of ammonium acetate on the two components of the multienzyme 2-oxoglutarate dehydrogenase complex (OGDH): 2-oxoglutarate decarboxylase (E1) and lipoamide dehydrogenase (E3), were examined in synaptic and nonsynaptic mitochondria from rat brain. With regard to E1 the response to ammonium ions in vitro (3 mM NH4Cl) was observed in nonsynaptic mitochondria only and was manifested by a 21% decrease of Vmax and a 35% decrease of Km for 2 oxoglutarate (2-OG). By contrast, both in vivo conditions primarily affected the synaptic mitochondrial E1: TAA-induced HE produced an 84% increase of Vmax and a 38% increase of Km for 2-OG. Hyperammonemia elevated Vmax of E1 by 110% and Km for 2-OG by 30%. HE produced no effect at all in nonsynaptic mitochondria while hyperammonemia produced a 35% increase of Vmax and a 30% increase of Km for 2-OG of E1. Both in vivo conditions produced a 20% increase of E3 activity in synaptic mitochondria, but no effect at all in nonsynaptic mitochondria. The preferential sensitivity of E1 to ammonium chloride in vitro in nonsynaptic mitochondria and hyperammonemic conditions in vivo in synaptic mitochondria may play a crucial role in the compartmentation of OGDH responses under analogous conditions. These results confirm the intrinsic differences between the OGDH properties in the synaptic and nonsynaptic brain compartments. PMID- 8474556 TI - Regulation of phosphate-activated glutaminase (PAG) by glutamate analogues. AB - The ability of structural analogues of glutamate (GLU) to modulate phosphate activated glutaminase (PAG) was assessed in the present series of studies. A number of GLU receptor agonists and antagonists were tested for their ability to inhibit synaptosomal PAG activity. PAG activity was determined by measuring GLU formation from 0.5 mM glutamine (GLN) in the presence of 10 mM phosphate. GLU analogues at 5-10 mM were found to significantly inhibit PAG activity. It was determined that PAG inhibition occurred regardless of whether the GLU analogues were receptor agonists or antagonists, however, PAG inhibition was influenced by analogue chain length, isomeric form and substituent substitution. The glutamate uptake blockers, dihydrokainic acid and DL-threo-beta-hydroxyaspartic acid were relatively weak inhibitors of PAG (< 25% inhibition) as were the receptor agonists, ibotenic acid and (+-)cis-2,3-piperidine-dicarboxylic acid. Other GLU analogues produced inhibition of PAG in the range of 40-70%. PAG inhibition by GLU analogues did not appear to differ substantially among the brain regions evaluated (cortex, striatum and hippocampus). The endogenous amino acids, glycine, taurine and N-acetylaspartic acid, also significantly inhibited PAG activity in the 5-10 mM range. The noncompetitive NMDA antagonists, (+)MK801 and ketamine, at a concentration of 5 mM, significantly stimulated PAG activity 1.5-2 fold over control values. The activation of PAG by (+)MK801 was dose-related, stereoselective and appeared to result from a synergistic interaction with phosphate to enhance substrate (GLN) binding to PAG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474557 TI - Neurons respond to hyposmotic conditions by an increase in intracellular free calcium. AB - The effect of hyposmotic conditions on the concentration of intracellular free calcium ([Ca2+]i) was studied in cultured cerebellar granule cells and cerebral cortical neurons after loading of the cells with the fluorescent Ca2+ chelator Fluo-3. It was found that in both types of neurons exposure to media with a decrease in osmolarity of 20 to 50% of the osmolarity in the isosmotic medium (320 mOsm) led to a dose dependent increase in [Ca2+]i with a time course showing the highest value at the earliest measured time point, i.e. 40 s after exposure to the hyposmotic media and a subsequent decline towards the basal level during the following 320 s. The response in the cortical neurons was larger than in the granule cells but both types of neurons exhibited a similar increase in [Ca2+]i after exposure to 50 mM K+ which was of the same magnitude as the increase in [Ca2+]i observed in the cortical neurons exposed for 40 s to a medium with a 50% reduction in osmolarity. In both types of neurons the blocker of voltage gated Ca2+ channels verapamil had no effect on the hyposmolarity induced increase in [Ca2+]i. On the contrary, this increase in [Ca2+]i was dependent upon external calcium and could be inhibited partly or completely by the inorganic blockers of Ca2+ channels Mg2+ and La3+. Dantrolene which prevents release of Ca2+ from internal stores had no effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474558 TI - Depletion of polyamines prevents the neurotrophic activity of the GABA-agonist THIP in cultured rat cerebellar granule cells. AB - Effects of polyamine depletion by alpha-difluoromethylornithine (DFMO) were studied on the GABA-agonist mediated enhancement of the morphological development of cultured rat cerebellar granule cells. An increase in the number of neurite extending cells and in the cytoplasmic density of organelles relevant for protein synthesis was observed upon culturing in the presence of 4,5,6,7-tetrahydro isoxazole[5,4-c]pyridin-3-ol (THIP) for 4 days. The intracellular concentrations of putrescine, spermidine, and spermine in these cultures were similar to the concentrations of the polyamines observed in cultures grown in a plain culture medium for 1, 2, 3 or 4 days, respectively. Upon culturing in the simultaneous presence of THIP and DFMO, the concentrations of putrescine and spermadine were reduced to less than 20% of the levels in the controls. This depletion was associated with a severely impaired morphological development of the granule cell cultures. Thus, the number of neurite extending cells was reduced to 50% of the number in the control cultures upon culturing in the presence of DFMO alone or in combination with THIP. Moreover, the THIP mediated increase in the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus and different types of vesicles was prevented by the exposure to DFMO. PMID- 8474559 TI - Transport of L-lactate by cultured rat brain astrocytes. AB - Several reports indicate that lactate can serve as an energy substrate for the brain. The rate of oxidation of this substrate by cultured rat brain astrocytes was 3-fold higher than the rate with glucose, suggesting that lactate can serve as an energy source for these cells. Since transport into the astrocytes may play an important role in regulating nutrient use by individuals types of brain cells, we investigated the uptake of L-[U-14C]lactate by primary cultures of rat brain astrocytes. Measurement of the net uptake suggested two carrier-mediated mechanisms and an Eadie-Hofstee type plot of the data supported this conclusion revealing 2 Km values of 0.49 and 11.38 mM and Vmax values of 16.55 and 173.84 nmol/min/mg protein, respectively. The rate of uptake was temperature dependent and was 3-fold higher at pH 6.2 than at 7.4, but was 50% less at pH 8.2. Although the lactate uptake carrier systems in astrocytes appeared to be labile when incubated in phosphate buffered saline for 20 minutes, the uptake process exhibited an accelerative exchange mechanism. In addition, lactate uptake was altered by several metabolic inhibitors and effectors. Potassium cyanide and alpha-cyano-4-hydroxycinnamate inhibited lactate uptake, but mersalyl had little or no effect. Phenylpyruvate, alpha-ketoisocaproate, and 3-hydroxybutyrate at 5 and 10 mM greatly attenuated the rate of lactate uptake. These results suggest that the availability of lactate as an energy source is regulated in part by a biphasic transport system in primary astrocytes. PMID- 8474560 TI - Modulation of a neuronal calmodulin mRNA species in the rat brain stem by reserpine. AB - Reserpine evokes transsynaptic impulse activity by depleting catecholaminergic neurotransmitters in the rat brain. Previous studies suggest a relationship between catecholaminergic activity and calmodulin concentration. In this report we employ Northern blot analysis to examine the effect of a single subcutaneous injection of reserpine on levels of calmodulin mRNA species which are preferentially expressed in neurons of the rat brain. Regional differences in mRNA levels were also investigated by in situ hybridization and drug-induced changes were noted particularly in specific regions of the rat brain stem. The riboprobe used in the in situ hybridization study recognized a 4.0 kilobase neuronal calmodulin mRNA species (NGB1), which was derived from the rat CaM1 gene. A calmodulin radio-immunoassay was utilized to demonstrate a drug-induced increased in calmodulin protein levels in a region which included the brain stem. PMID- 8474561 TI - Spontaneous and evoked release of [3H]taurine from a P2 subcellular fraction of the rat retina. AB - The effects of spontaneous and evoked [3H]taurine release from a P2 fraction prepared from rat retinas were studied. The P2 fraction was preloaded with [3H]taurine under conditions of high-affinity uptake and then examined for [3H]taurine efflux utilizing superfusion techniques. Exposure of the P2 fraction to high K+ (56 mM) evoked a Ca(2+)-independent release of [3H]taurine. Li+ (56 mM) and veratridine (100 microM) had significantly less effect (8-15% and 15-30%, respectively) on releasing [3H]taurine compared to the K(+)-evoked release. 4 Aminopyridine (1 mM) had no effect on the release of [3H]taurine. The spontaneous release of [3H]taurine was also Ca(2+)-independent. When Na+ was omitted from the incubation medium K(+)-evoked [3H]taurine release was inhibited by approximately 40% at the first 5 minute depolarization period but was not affected at a second subsequent 5 minute depolarization period. The spontaneous release of [3H]taurine was inhibited by 60% in the absence of Na+. Substitution of Br- for Cl- had no effect on the release of either spontaneous or K(+)-evoked [3H]taurine release. However, substitution of the Cl- with acetate, isethionate, or gluconate decreased K(+)-evoked [3H]taurine release. Addition of taurine to the superfusion medium (homoexchange) resulted in no significant increase in [3H]taurine efflux. The taurine-transport inhibitor guanidinoethanesulfonic acid increased the spontaneous release of [3H]taurine by approximately 40%. These results suggest that the taurine release of [3H]taurine is not simply a reversal of the carrier mediated uptake system. It also appears that taurine is not released from vesicles within the synaptosomes but does not rule out the possibility that taurine is a neurotransmitter. The data involving chloride substitution with permeant and impermeant anions support the concept that the major portion of [3H]taurine release is due to an osmoregulatory action of taurine while depolarization accounts for only a small portion of [3H]taurine release. PMID- 8474563 TI - Stress protein synthesis and accumulation after traumatic injury of crayfish CNS. AB - By several days after a crush injury of crayfish CNS, the wound site heals. Changes in protein synthesis and accumulation occur at the lesion site and nearby. During the first few hours, synthesis of 35, 70, 90, and 150 kDa proteins is induced in the injured tissue. By one day, the relative amounts of 70-90 kDa proteins increase dramatically, particularly at the crush site and adjacent to it. The 70 kDa proteins, which are related to mammalian stress proteins (SPs), remain elevated for at least one month in the traumatized region or nearby. The crushed tissue contains an SP70 isoform not present in its uncrushed counterpart. These biochemical changes may reflect the cellular changes that accompany wound healing and/or a cellular stress response to compensate for the lesion. Since similar adaptations occur in the mammalian CNS, they may represent a phylogenetically conserved attempt to retard or repair CNS tissue deterioration. PMID- 8474564 TI - Specificity of calcium-activated neutral proteinase (CANP) inhibitors for human mu CANP and mCANP. AB - We investigated the relative inhibition of purified human mu CANP and mCANP by five cysteine proteinase inhibitors including N-acetyl-Leu-Leu-nor-leucinal (C-I) and N-acetyl-Leu-Leu-methioninal (C-II), calpeptin, E64, and leupeptin. Based on IC50 measurements, calpeptin and C-I were stronger inhibitors by one to two orders of magnitude than C-II, leupeptin or E64. None of the five inhibitors, however, exhibited greater specificity for human mu CANP or mCANP. These results indicate that, although the inhibition of a given cellular event by these compounds may suggest CANP involvement, effects on mu CANP cannot be discriminated from those on mCANP. PMID- 8474562 TI - Quantitative alterations of S-100 protein and neuron specific enolase in the rat nervous system after chronic 2,5-hexanedione exposure. AB - The regional changes in quantities of the glial S-100 protein and the neuron specific enolase in the rat nervous system have been studied after long-term exposure to 2,5-hexanedione. The wet weights of most of the examined nervous tissues were found to be reduced, with an extensive effect seen in the brain stem. Using dot immunobinding assays, the concentrations of S-100 were found to be increased in most of the examined tissues, but unaffected in the brain stem. The total amount of S-100 per tissue was markedly reduced in the brain stem. The content of neuron specific enolase was reduced only in the brain stem. Thus the effects of 2,5-hexanedione on the nervous system varied regionally. The brain stem was severely atrophied with a reduction of neuronal as well as of glial marker proteins. Other brain regions contained increased glial cell marker proteins as signs of progressive astroglial reactions. PMID- 8474565 TI - Special issue dedicated to Dr. Claude Baxter. PMID- 8474566 TI - Heterogeneous distribution of functionally important amino acids in brain areas of adult and aging humans. AB - The regional distribution of seven amino acids thought to have inhibitory neurotransmitter or neurotransmitter precursor function--GABA, glycine, taurine, serine, threonine, phenylalanine, and tyrosine--was determined in 52 discrete areas from brain of adult and old humans. Significant heterogeneity was found, with 3- to 16-fold differences in levels in the various regions analyzed. The patterns of distribution were somewhat different from those in the adult or old rat brain. Relatively few changes were seen in old brain. Heterogeneity in distribution has to be taken into account in assessing physiological changes in amino acid levels and metabolism. PMID- 8474567 TI - Taurine in toad brain and blood under different conditions of osmolality: an immunohistochemical study. AB - The concentrations of taurine in blood and brain regions of the toad Bufo boreas have been measured. Most of these values are considerably lower than those found in mammals. Using an antibody prepared against conjugated taurine, the distribution of taurine in three brain regions of the toad has been visualized. The possible osmoregulatory functions of taurine have been investigated by making toads hyper- or hypo-osmotic in vivo. Induction of hypoosmolality is accompanied by a massive taurine tide in blood plasma, but has no immediate effects upon the taurine concentrations in the brain areas studied. However, histochemical visualization indicates a marked redistribution of taurine between cellular components and extracellular space of brain tissues. This may indicate that taurine has an osmoregulatory function in brain tissue under hypo-osmotic conditions. Hyperosmolality results in no elevation of the taurine concentration in blood plasma of toads, but rather in a very gradual decline of total plasma taurine content over a prolonged time period. Histochemical studies reveal little change in frontal cortex after 1 hour but deeper staining of many neurons in optic lobe accompanied by greater staining in the extracellular fluid. By 3 hours there is a depletion of taurine from all compartments of cerebral cortex tissues. No evidence of any prolonged direct osmoregulatory role for taurine is indicated under hyperosmotic conditions. A possible indirect osmoregulatory function of taurine is discussed. PMID- 8474568 TI - Modulation by GABA of neuroplasticity in the central and peripheral nervous system. AB - Apart from being a prominent (inhibitory) neurotransmitter that is widely distributed in the central and peripheral nervous system, gamma-aminobutyric acid (GABA) has turned out to exert trophic actions. In this manner GABA may modulate the neuroplastic capacity of neurons and neuron-like cells under various conditions in situ and in vitro. In the superior cervical ganglion (SCG) of adult rat, GABA induces the formation of free postsynaptic-like densities on the dendrites of principal neurons and enables implanted foreign (cholinergic) nerves to establish functional synaptic contacts, even while preexisting connections of the preganglionic axons persist. Apart from postsynaptic effects, GABA inhibits acetylcholine release from preganglionic nerve terminals and changes, at least transiently, the neurochemical markers of cholinergic innervation (acetylcholinesterase and nicotinic receptors). In murine neuroblastoma cells in vitro, GABA induces electron microscopic changes, which are similar in principle to those seen in the SCG. Both neuroplastic effects of GABA, in situ and in vitro, could be mimicked by sodium bromide, a hyperpolarizing agent. In addition, evidence is available that GABA via A- and/or B-receptors may exert direct trophic actions. The regulation of both types of trophic actions (direct, receptor-mediated vs. indirect, bioelectric activity dependent) is discussed. PMID- 8474569 TI - The role of GABA during development of the outer retina in the rabbit. AB - Horizontal cells are among the first to mature in the neonatal mammalian retina and they are the first to establish the position of the outer synaptic layer which is subsequently formed by invading terminals of both rod and cone photoreceptors. During the period of cone synaptogenesis, horizontal cells transiently express the full complement of GABAergic properties (uptake, release, synthesis and storage of GABA); later during development of rod terminals, these properties are down-regulated. Given the reports of GABA's role in other developing neuronal systems (for review: 10), we have examined the effect that GABA, produced from horizontal cells, might have on photoreceptor maturation in rabbit retina. Results from our previous studies show that lesioning the horizontal cell with kainic acid in vivo leads to a displacement of cone photoreceptor cells and a disappearance of their synaptic terminals, while rod cells maintain their normal position and produce an overabundance of terminals. Similar effects are seen with the GABA-A receptor antagonists, picrotoxin and bicuculline. New evidence from 3H-thymidine studies suggests that the effects of kainic acid are specific and that cell division, migration and differentiation in other cell types do not appear to be affected. This body of work is summarized and possible mechanisms of action are suggested which could account for the apparent ability of GABA to help maintain the normal position of cone cell bodies and regulate cone synaptogenesis. PMID- 8474570 TI - Biochemical correlates to cortical dysplasia, gliosis, and astrocytoma infiltration in human epileptogenic cortex. AB - The study provides detailed biochemical correlates to the common histopathological diagnoses in epilepsy. A dot immunobinding procedure was used for quantification of NSE, GFA, S-100, NCAM, NF 68 and NF 200. The material consisted of samples from 48 patients either selected for surgical treatment of partial epilepsy or for disorders not related to epilepsy. The histopathological diagnosis of the epileptic cases was: MCD (mild cortical dysplasia, microdysgenesis), gliosis, astrocytoma, ganglioglioma, oligodendroglioma and single cases. The concentration in non-epileptic white matter, in per cent of that in grey matter was: NSE, 85; GFA, 175; S-100, 117; NCAM, 43; NF 68,227 and NF 200, 173. The concentration of NSE as well as of GFA was close to normal in the specimens of the MCD and gliosis groups and of one subgroup of the astrocytomas. There was a striking inverse relationship of the GFA vs the NSE concentrations in the whole material. The concentrations of S-100 showed no such inverse relationship to NSE levels. In all the epileptic groups, total NCAM was lower than 50% of that of the non-epileptic group. The mean NF 68 and NF 200 concentration in the gliosis and astrocytoma groups was 75% of that of the non epileptic group while the corresponding value for the MCD group was 50%. There was a positive correlation of immunochemically determined GFA and the histopathological gliosis score in the samples of epileptogenic cortex. There was no correlation between the concentration of GFA in the samples and the duration of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474571 TI - GABA metabolism in the substantia nigra, cortex, and hippocampus during status epilepticus. AB - The metabolism of GABA and other amino acids was studied in the substantia nigra, the hippocampus and the parietal cortex of rats following microinjections of GAMMA-vinyl-GABA during status epilepticus induced by lithium and pilocarpine. GABA metabolism showed striking regional variations. In controls, both GABA concentration and rate of GABA synthesis were highest in the substantia nigra and lowest in cortex, as expected. In substantia nigra, status epilepticus resulted in a 2 1/2 fold decline in the rate of GABA synthesis and in a 307% increase in the turnover time of the GABA pool. In hippocampus, the rate of GABA synthesis was not altered significantly, but the turnover time of the GABA pool was 284% of controls, and the size of that pool increased to 208% of controls. By contrast, in cortex, where seizure activity is limited in this model, the rate of GABA synthesis increased to 230% of controls while pool size and turnover time did not change. Aspartate concentration decreased in all three brain regions. These data suggest that the observed reduction of the rate of GABA synthesis in substantia nigra could play a key role in seizure spread in this model of status epilepticus. PMID- 8474572 TI - Effects of GABAmimetics on electrocorticographic spike discharges induced by guanidinoethanesulfonic acid (amidino-taurine) in the rat. AB - The effect of guanidinoethanesulfonic acid (GES) on rat electrocorticograms (ECoG) and the effects of gamma-aminobutyric acid (GABA) and GABA-agonists on the ECoG changes induced by GES were studied. Sporadic spike discharges began 2-5 min after 1 mumol GES/10 microliters on filter paper was applied to the pia mater of the left sensorimotor cortex; spike discharges extended to the opposite cerebral hemisphere 60 min after the onset of the ipsilateral spike discharges. The spike discharges with a frequency of 5-10 spikes/min lasted until the end of the 4 hour recording. The induced spike discharges were suppressed when the original GES soaked filter paper was replaced by one containing GES (1 mumol) supplement combined with taurine (1 mumol/10 microliters). GABA (1 mumol) and its receptor agonist, muscimol (10 nmol) and (3R)-(-)-4-amino-3-hydroxybutyric acid (1 mumol) also suppressed the GES-induced spike discharges when applied topically. Diazepam (DZP) (10 mg/kg) suppressed the GES-induced spike discharges 10 min after i.p. injection, but phenobarbital (20 mg/kg) increased the frequency and voltage of spike discharges 100 min following subcutaneous administration. Intraperitoneal injection of either valproate (200 mg/kg) or phenytoin (25 mg/kg), after the completion of the spike discharges, showed no effect. These findings suggest that neurotransmission or neuromodulatory effects of taurine participate in GES induced seizure activity, and that GABAA and DZP receptors may play a role in the mechanism that suppresses GES-induced seizures. PMID- 8474573 TI - Effects of inhibition of ornithine aminotransferase on thioacetamide-induced hepatogenic encephalopathy. AB - Repeated administration of thioacetamide (TAA) to CD1 mice produced hepatic failure and biochemical and behavioral effects characteristic of hepatogenic encephalopathy (HE). The symptoms in mice resembled those previously observed in rats after similar treatments. It is, however, obvious that both in rats and mice the severity of symptoms depends not only on dose and dosing schedule of TAA, but also on strain and body weight (age). Administration of 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase (OAT), significantly reduced mortality, and it ameliorated most of the TAA-induced pathologic symptoms, such as hypothermia, decreased locomotor and exploratory behavior, pathologic liver function and amino acid patterns. The most prominent biochemical consequence of 5FMOrn administration is the elevation of ornithine concentrations in tissues, including the brain, and in body fluids. Elevated ornithine concentrations are, therefore, the most likely basis for the therapeutic effects of 5FMOrn. In agreement with this notion is the enhancement of citrulline and urea formation. These findings and the observation that administration of ornithine in combination with a branched-chain 2-oxoacid ameliorated the pathologic symptoms of portal-systemic encephalopathy suggest inhibition of OAT in the treatment of this disease. The liver protective effect of 5FMOrn is not yet understood; the enhancement of regenerative processes is a likely explanation. PMID- 8474574 TI - Ethanol exerts differential effects on high affinity choline uptake in neuron enriched cultures from 8-day-old chick embryo cerebral hemispheres. AB - Neuronal-enriched cultures were prepared from 8-day-old chick embryo cerebral hemispheres and exposed to ethanol (50 mM) from day 4 to 8 in culture. At day 8, both control and ethanol-treated cultures were processed for [3H]choline uptake in situ. Uptake was performed on cultures containing either Na(+)-plus or Na(+) free (Li+) HEPES buffer. Total choline uptake as well as Na(+)-dependent and Na(+)-independent choline uptake were calculated. The Km and Vmax were calculated using the Lineweaver-Burke analysis. Our analysis of the data revealed that ethanol-treated cultures exhibited two values for Vmax, one similar to that found in control cultures and one significantly lower than controls. No differences were observed in Km values between control and ethanol-treated cultures. We interpret the low Vmax to represent a population of cholinergic neurons which have been arrested at an immature stage as a result of ethanol insult. PMID- 8474575 TI - Asymmetric distribution and down-regulation of the muscarinic acetylcholine receptor in rat cerebral cortex. AB - The distribution and down-regulation of the muscarinic acetylcholine receptor (mAChR) were studied in dissociated cells from right (RCC) and left (LCC) cerebral cortex. For this purpose [3H]quinuclidinyl benzilate (QNB) and [3H]pirenzepine (Pz), two muscarinic antagonists, were used. The mAChR binding sites detected with [3H]QNB were asymmetrically distributed between the two hemispheres, the majority being found in the RCC. Asymmetry was also evident in the distribution of the mAChR subtypes (M1 and M2) detected with [3H]Pz. Under basal conditions the RCC had roughly 50% more M1 subtype than the LCC. The pharmacological and kinetic parameters were similar for both antagonists in RCC and LCC, indicating that the observed lateralization was due to a different density of the receptor rather than to different kinetics of binding of the two radioligands. After sustained stimulation with the agonist carbamoylcholine, the receptor sites detected with [3H]Pz, i.e. the M1 subtype of mAChR, decreased at a higher rate in the RCC (44%) than in the LCC (25% of controls), demonstrating that the down-regulation process is more active in the right than in the left cortex, and thus implying that there is better coupling between the stimulated mAChR and its effector system in the former. PMID- 8474576 TI - Effect of acetyl-L-carnitine on extracellular amino acid levels in vivo in rat brain regions. AB - Acetyl-L-carnitine (ALCAR) was found to have beneficial effects in senile patients. In recent years many of its effects on the nervous system have been examined, but its mechanism(s) of action remains to be elucidated. We previously reported that it causes release of dopamine in the striatum. In the present paper we report that ALCAR, when administered at intracerebral sites via microdialysis, stimulates the release of amino acids in a concentration-dependent and regionally heterogeneous manner. The effect was strong in the striatum and cerebellum, less so in the frontal cortex, and weak in the thalamus. Seven amino acids were measured: the increase in the level of aspartate, glutamate, and taurine was substantial, and the increase in the level of glycine, serine, threonine, alanine, and glutamine in the microdialysate was minor. The stimulatory effect of ALCAR on the release of amino acids in the striatum was inhibited by the muscarinic antagonist atropine, but was not inhibited by the nicotinic antagonist mecamylamine. The effect of ALCAR on the levels of most of the amino acids tested was independent of the presence of Ca2+ in the perfusate. These results indicate that ALCAR, when administered intracerebrally at fairly high concentrations, can affect the level and the release not only of such neurotransmitters as acetylcholine and dopamine, but also of amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474577 TI - Blood-brain glucose transfer in the mouse. AB - The intracarotid injection method has been utilized to examine blood-brain barrier (BBB) glucose transport in normal mice, and after a 2-day fast. In anesthetized mice, cerebral blood flow (CBF) rates were reduced from 0.86 ml.min 1 x gm-1 in control to 0.80 ml.min-1 x gm-1 in fasted animals (p > 0.05). Brain Uptake Indices were significantly (p < 0.05) higher in fasted (plasma glucose = 4.7 mM) than control (plasma glucose = 6.5 mM) mice, while plasma glucose was significantly lower. The maximal velocity (Vmax) for glucose transport was 1562 +/- 303 nmoles.min-1 x g-1, and the half-saturation constant (Km =) 6.67 +/- 1.46 mM in normally fed mice. In fasted mice the Vmax was 2053 +/- 393 nmoles.min-1 x g-1 (p > 0.05), and the half-saturation constant (Km =) 7.40 +/- 1.60 mM (not significant, P > 0.05). A rabbit polyclonal antiserum to a synthetic peptide encoding the 13 C-terminal amino acids of the human erythrocyte glucose transporter (GLUT-1) immunocytochemically confirmed that the mouse brain capillary endothelial glucose transporter is a GLUT-1 transporter, and immunoreactivity was similar in brain endothelia from fed and fasted animals. In conclusion, after a 2-day fast in the mouse, we saw significant reductions in forebrain weight (7%), and plasma glucose levels (27%). Increased brain glucose extraction (25%, p < 0.05), and a 22% increase in the unsaturated permeability surface area product (p < 0.05) was also observed. PMID- 8474578 TI - Gangliosides in acetylcholine receptor-rich membranes from Torpedo marmorata and Discopyge tschudii. AB - The ganglioside composition of membranes enriched in nicotinic acetylcholine receptor (AChR) from the electric rays Discopyge tschudii and Torpedo marmorata has been determined, and compared to that of total electric organ. A ganglioside having the chromatographic mobility of GM2 constitutes the major ganglioside (approximately 60%) in total D. tschudii electric organ, followed by a component with the mobility of GD3 (approximately 10%), and a component running just below GD1a (about 12%). Minor constituents running as GM3 (2%) and as polysialogangliosides (comprising 8-15%) were also observed. Purified native membranes of D. tschudii and T. marmorata displayed a similar profile, except that they were richer in a GM1-like component, and the proportion of GM2-like gangliosides was lower than that in total electric organ. Using a 125I-cholera toxin overlay assay on neuraminidase-treated high-performance thin layer chromatograms, the presence of GM1, GD1a and trace amounts of GD1b and GT1 (or GQ) were detected in D. Tschudii total membranes. Immunocytochemical trechniques showed the co-localization of gangliosides GQ1c/GT1c/GP1c, recognized by the monoclonal antibody Q211, and the AChR at the ventral, innervated face of the electrocyte. PMID- 8474579 TI - Electroconvulsive shock does not modify striatal contents of dopamine in MPTP treated mice. AB - It has been suggested that the therapeutic response to electroconvulsive therapy in depressed patients could be mediated by functional changes in the dopaminergic pathways; a favorable response to electroconvulsive therapy was also observed recently in patients with Parkinson's disease. To study a possible interference of electroconvulsive shock in the course of MPTP-induced parkinsonism in rodents, we measured the striatal content of dopamine in MPTP-treated mice that received electroconvulsive shock at various intervals in the course of MPTP neurotoxicity. Our results showed no immediate or delayed differences in striatal dopamine content of animals that received MPTP and electroconvulsive shock when compared with animals that received only MPTP, thus suggesting that the strong biological effects of MPTP and electroconvulsive shock on the brain may follow different biochemical mechanisms. PMID- 8474580 TI - Modulation of potassium evoked secretory function in rat cerebellar slices measured by real time monitoring: evidence of a possible role for methylfolate in cerebral tissue. AB - The real time dynamics of K+ evoked neurosecretion in cerebellar slices has been monitored electrochemically. In the presence of 5-methyltetrahydrofolate a statistically significant diminution in secretory response occurs. Agonists to probe the pharmacological basis for this indicate it is not due to voltage sensitive Ca2+ channel blockade, nor does it show any similarity of effect with kainate, whose receptor is a putative binding site for 5-methyltetrahydrofolate. The method is fully validated, although no account is taken of individual molecular species. High performance liquid chromatography combined with off line microbiological assay could only detect 5-methyltetrahydrofolate in cerebrospinal fluid. We therefore discuss our findings in relation to possible cerebral roles for cerebrospinal fluid 5-methyltetrahydrofolate in the context of both membrane and transmitter related interactions. PMID- 8474581 TI - Radio-label and mass determinations of inositol 1,3,4,5-tetrakisphosphate formation in rat cerebral cortical slices: differential effects of myo-inositol. AB - To investigate the effects of increasing concentrations of myo-inositol (inositol) on receptor stimulated [3H]inositol polyphosphate formation in the absence of lithium, slices of rat cerebral cortex were incubated with various concentrations of [3H]inositol (1 to 30 microM). Carbachol stimulated formation of [3H]inositol trisphosphate (InsP3) and [3H]inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) increased several fold when the inositol concentration was increased reaching a plateau at approximately 12 microM inositol. Time course studies revealed that in the presence of low concentrations of inositol (1 microM), [3H]InsP3 and [3H]Ins(1,3,4,5)P4 formation in response to carbachol stimulation increased slowly over a 10 to 20 min time period, whereas in the presence of 4 and 12 microM inositol, carbachol stimulated [3H]InsP3 and [3H]Ins(1,3,4,5)P4 formation was rapid and essentially complete within 3 to 5 min after carbachol addition. Although the carbachol dose response in 12 microM inositol had a much greater maximal efficacy, there was no change in potency. Similar to the effects of carbachol on [3H]Ins(1,3,4,5)P4 formation from prelabeled phosphoinositides, muscarinic receptor stimulation increased Ins(1,3,4,5)P4 mass formation by seven fold. Furthermore, Li+ (8 mM) completely inhibited carbachol stimulated increases in Ins(1,3,4,5)P4 mass formation. In contrast to the effects of increasing inositol on carbachol stimulated formation of radiolabeled inositol phosphates, increasing inositol had no effect upon mass formation of Ins(1,3,4,5)P4. These results show that when measuring inositol polyphosphate formation by the radiolabeling technique in the absence of Li+, increasing the inositol concentration greatly increases the stimulated component of [3H]InsP3 and [3H]Ins(1,3,4,5)P4 formation. However, this inositol induced increase in agonist stimulated Ins(1,3,4,5)P4 formation is not reflected as an increase in mass formation. PMID- 8474582 TI - [Cerebral blood flow and oxygen metabolism: estimation by PET; with special respect to ischemic cerebrovascular disorders (series 4)]. PMID- 8474583 TI - [Vasospasm and its outcome after early surgery for ruptured cerebral aneurysms: changing pattern of its incidence and outcome during this 9-year period]. AB - The occurrence and outcome of vasospasm (VS) were analyzed in 240 patients who had aneurysm surgery within 7 days of a hemorrhage during 9-year period (1981 89). Occurrence of VS was evaluated by the appearance of ischemic symptoms, (A) with or (B) without CT evidence of infarcts. The surgical outcome was assessed by the Glasgow Outcome Scale 6 months postoperatively. The results in the first and the latter halves of the period were compared. The overall incidence of VS (A+B) was 34.8% (A: 23.5%, B: 11.3%) and 33.6% (A: 15.2%, B: 18.4%) in the first and the latter halves, respectively. Thus, VS leading to infarction showed a tendency to decrease in the latter half of the period, though the overall incidence of VS itself was almost identical in both the first and second halves of the period. The results were also analyzed according to preoperative grading based on the Glasgow Coma Scale (GCS). The tendency toward decreased severity of VS in the latter term was most remarkable in patients with GCS total scores between 14 and 13. The decreased incidence of severe VS proved to be reflected in decreased mortality and in increased rate of good outcome in the latter half of the period. In order to confirm whether the results obtained in our clinic are universal, we applied the same analysis for control groups in four cooperative double-blind clinical trials performed during this period in Japan. The study again showed that the rate of infarction has decreased significantly over the decade, resulting in the improved surgical outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474584 TI - [Usefulness and limitation of MR imaging and MR angiography in diagnosis of juvenile moyamoya disease]. AB - Magnetic resonance (MR) images and MR angiograms (MRA) were studied in 20 childhood cases of moyamoya disease. Both MRI and MRA successfully demonstrated moyamoya vessels in the basal ganglia in all cases, with a positive but not definite correlation to the conventional angiographic findings. MRI depicted the stenotic and occlusive lesions of the carotid fork and horizontal portion of the middle cerebral artery effectively. MRA demonstrated some lesions which even MRI failed to prove, but it tended to overestimate the lesions. Post-operative state of collateral flow and the patency of EC-IC bypass graft could be evaluated as accurately with MRA as with conventional angiography, although MRA was limited in spatial resolution and evaluation of flow direction. In conclusion, MRI and MRA were considered to be useful in the diagnosis of moyamoya disease in stage 3 and 4, but less effective in the evaluation of its angiographical stage. PMID- 8474585 TI - [Clinical application of calculation software of the four rules of arithmetic on computed tomography]. AB - Calculation program software of the four rules of arithmetic in computed tomography (CT) has been introduced for clinical purposes since 1990. Evaluation of hemodynamic reserve and cerebral autoregulation can be calculated using this software in ischemic cerebrovascular diseases and delayed cerebral vasospasm after ruptured intracranial aneurysms. Eight hemodynamic maps can be entered and calculation based on the four rules of arithmetic can be performed between them and shown visually. For example, delta CBF [CBF after administration of acetazolamide (B)-CBF before its administration(A)] and % CBF [(B - A)/A x 100] maps are useful in evaluation of the capacity of hemodynamic reserve in ischemic cerebrovascular diseases. And delta CBF [CBF before induced hypertension using intravenous dopamine administration (B)-CBF during induced hypertension (A)] and % CBF [(B - A)/A x 100] also can be used in evaluation of cerebral autoregulation and decision concerning indication of the need for induced hypertension during the period of delayed cerebral vasospasm after subarachnoid hemorrhage. PMID- 8474587 TI - [Effects of the cervical spinal cord stimulation on persistent vegetative syndrome: experimental and clinical study]. AB - Influence of spinal cord stimulation (SCS) on electroencephalograms (EEGs) and intracerebral neurotransmitters were studied in cats, and clinical usefulness of the stimulation was reviewed in patients with vegetative syndrome. Cat spinal cords were transdurally stimulated at the second cervical spine for two hours with a pulse width of 1.0 milliseconds, a frequency of 200 Hz and an amplitude ranging from 10 to 15 volts. EEGs were recorded at the frontal epidural space and neurotransmitters in the frontal cortex, such as acetylcholine (ACh), 5 hydroxyindoleacetic acid (5-HIAA), aspartate, glutamate and gamma-aminobutyric acid (GABA), were measured by an in vivo microdialysis method. The background activities of the EEGs were increased by 2 Hz after the SCS. The ACh content increased to 320% three hours after initiation of the SCS, although the other four neurotransmitters did not show any change. Epidural SCS at the upper cervical level was applied to 15 vegetative patients for the amelioration of their vegetative state. Eleven of the 15 patients were treated later than three months after the onset of vegetative state and the other four within three months. Three of the 11 patients treated late and one of the four treated early escaped from the vegetative state (good group). Some clinical improvements were observed in four cases (fair group), two of whom were treated late and the other treated early. The other seven patients showed no improvement (no change group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474586 TI - [MR findings in traumatic cerebrospinal fluid leakage with special reference to indications of the need for dural repair]. AB - Eleven cases of traumatic cerebrospinal fluid (CSF) leakage (8 cases of rhinorrhea and 3 cases of otorrhea) were reviewed to discuss magnetic resonance (MR) findings and surgical indications of the need for dural repair. Five patients had delayed onset of CSF rhinorrhea, 12 to 66 days (mean 28 days) after the trauma, and in the remaining 6 patients (3 rhinorrhea and 3 otorrhea) CSF leakage was noted on admission. MR study was carried out within 7 days after the onset of CSF leakage using a 0.5 tesla imager. In 7 cases of rhinorrhea, MR images demonstrated brain herniation into the ethmoid or frontal sinuses and the dural defects were repaired with the vascularized periosteum flap taken from the frontal bone or the fascia lata. In the operations, brain parenchyma was found to be plugged into the fracture line as MR images showed, and also to adhere to the margin of dural fistula. In the remaining 4 patients (without the MR findings of brain herniation into the paranasal sinuses) spontaneous cessation of CSF leakage occurred and their clinical course was good. Spontaneous cessation of CSF leakage in these cases may suggest the complete healing of the lacerated dura. However, in cases with the brain herniated into the paranasal sinuses CSF leakage may not be observed, and natural healing of the dural defect cannot be expected. Therefore, such brain herniation indicates the absolute need for dural repair even if CSF leakage is not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474588 TI - [Markedly dilated cervical carotid arteries in a patient with a ruptured aneurysm of the anterior communicating artery: a case report]. AB - We reported a case of ruptured aneurysm of the anterior communicating artery with marked dilatation of bilateral cervical carotid arteries. A 38 year old female suffered a subarachnoid hemorrhage. Angiography on admission revealed markedly dilated cervical carotid arteries with smooth lumen and a few segmental areas with mild constrictions in their entire course up to the carotid canals (their maximal sagittal diameters exceeded those of a cervical vertebral body). A saccular aneurysm was also seen at the junction of right A1, A2, and Acom. External carotid arteries were normal in size. Vertebral arteries were not examined because of failures of selective cannulation. The patient was operated upon and trapping of Acom was performed. During the operation, no definite arteriosclerotic changes were identified in the intracranial arteries. Histopathological examination of the surgical specimens revealed marked hyperplasia of the smooth muscle of the tunica media with intact internal elastic lamina both in a superficial temporal artery and a middle meningeal artery. During the operation, pneumothorax developed due to the rupture of bullae in the right lung. Past history of this patient disclosed hypertension noted a few years previously, and frequent severe bruises following minor trauma. Repeated angiography performed three months after the operation disclosed unchanged dilatation of the cervical carotid arteries as well as mild intraluminal irregularities in the proximal one third of the left renal artery. This patient died of pneumonia one year after the operation, but autopsy was not permitted. Possible diagnosis of this patient was discussed, with particular emphasis on fibromuscular dysplasia and Ehlers-Danlos type IV (arterial, ecchymotic, or Sack Barabas type).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474589 TI - [Eighth cranial neuritis difficult to differentiate from intracanalicular acoustic neurinoma on MRI: case report]. AB - A patient with an enhancing, completely intracanalicular mass on MRI was presented. He had noticed progressive hearing loss in the left ear with tinnitus. Neurological examination revealed no abnormality except decreased hearing in the left ear. There were no other cranial nerve or cerebellar signs. An audiogram revealed profound hearing loss on the left ear with no ability of speech discrimination. Brainstem auditory evoked response was absent on the left. MRI enhanced with gadolinium-DTPA demonstrated an intracanalicular enhancing lesion on the left which was presumed to be an intracanalicular acoustic neurinoma. The patient underwent a left suboccipital craniectomy. The eighth cranial nerve appeared normal in the cerebellopontine angle cistern, and was swollen and discolored in the internal auditory canal. It was removed piecemeal. The patient remained deaf in the left ear postoperatively. Histopathologically, the lesion consisted of edematous nerve fiber and inflammatory cells, but no tumor cell was present within the specimen. The patient was diagnosed as having neuritis. The clinical time course of symptoms in our patient was not unusual for an acoustic neurinoma. It seems that the distinction between an intracanalicular acoustic neurinoma and other lesions cannot be made on basis of MR imaging alone. All available imaging modalities should be considered before a definitive surgical procedure is undertaken. PMID- 8474590 TI - [A case of endodermal sinus tumor in the basal ganglia associated with Down's syndrome]. AB - A case of Down's syndrome accompanied by endodermal sinus tumor of the left basal ganglia is reported. She was referred to us because of right hemiparesis. A CT scan showed a calcified mass in the left basal ganglia, which was well enhanced on contrast CT. Emergency removal of the tumor was performed because of its rapid growth, intratumoral hemorrhage, and acute hydrocephalus. The histological diagnosis established after surgery was endodermal sinus tumor. Alphafetoprotein positive cells were seen in the resected tumor by light microscopy. Postoperative irradiation was very effective, and the high level of serum alphafetoprotein decreased during the course of irradiation. The residual tumor, enhanced on contrast CT, was treated by administration of cisplatin and etoposide after irradiation. Cases of malignant tumors other than leukemia, which are associated with Down's syndrome, are extremely rate. To our knowledge, including three cases of germ cell tumor, there have been only nine cases of brain tumors associated with Down's syndrome reported previously. PMID- 8474591 TI - [Fibromuscular dysplasia with an internal carotid artery web on the angiograms]. AB - A 58-year-old woman experienced a transient right-sided hemianopsia. She also had difficulty finding words and trouble naming parts of objects. On admission, three days later, there were no signs of residual neurological deficit. Laboratory studies showed findings of neither diabetes mellitus, hypertension nor cardiac disease. Her serum cholesterol level was normal. No bruit was heard over the head and neck. Preoperative angiograms showed a discrete web (septum) at the left internal carotid origin (Fig. 2). 123I-IMP SPECT revealed a decreased areas of perfusion mainly in the left middle cerebral artery distribution (Fig. 3A). A reconstructive operation was performed. A firm discrete nonatherosclerotic ridge (septum) protruding into the vessel lumen was resected. Microscopic examination of the surgical specimen demonstrated intimal fibroplasia, a rare subtype of fibromuscular dysplasia (FMD). Postoperatively, hypoperfused areas in SPECT were improved (Fig. 3B). The patient has been free of symptoms to the present time (for about one year). In addition to the rarity of the lesion, the available data suggest that web-like subtype of FMD is apt to be associated with an increase in the risk of hemodynamic compromise and thromboembolism. Surgical therapy is recommended, especially for symptomatic patients. PMID- 8474592 TI - [An experience of dissecting cerebral aneurysm of the anterior cerebral artery]. AB - Intracranial dissecting aneurysms have been reported occasionally in recent years. However, excluding dissecting aneurysms which extend from the proximal intracranial carotid artery, dissecting aneurysms arising merely in ACA are found only rarely. We are reporting here a case of a 42 year-old gentleman who did not present any particular causative etiology such as trauma or other basic diseases causing arteritis. Our patient is the 8th case, as far as we could find in the literature, in which the dissection of the arterial wall originated at the ACA. The patient was thought to have a tiny saccular aneurysm at the A 1-2 junction of the right ACA associated with vasospasm in the distal ACA on the angiogram. The patient had motor weakness on the left side and headache as well as a low density area in the territory of the ACA on the CT scan. A craniotomy was performed verifying the aneurysm to be dissecting in type without any sign of recent subarachnoid hemorrhage in the surrounding structures. No aggressive surgical treatment such as trapping of the aneurysm was done because the collateral blood circulation in that territory of the distal right ACA seemed to be poor and the patient no longer had neurological deficit at the time of operation. The patient was treated successfully with antiplatelet therapy. On the follow-up angiogram performed 3.5 months after the onset of the illness, we noted the disappearance of the abnormal angiographical findings of the dissecting aneurysm and distal arterial narrowing (pearl and string sign).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474593 TI - [A juvenile male prolactinoma: a case report]. AB - Male prolactinomas often become voluminous and invasive, and also show higher serum prolactin levels due to delay of diagnosis. We experienced a case of prolactinoma in a 15-year-old boy. He was admitted with a complaint of visual disturbance. CT and MRI showed intra- and suprasellar mass with a ring enhancement and niveau formation suggesting intratumoral hemorrhage. By the right subfrontotemporal approach, subtotal tumor removal was performed, and intratumoral hemorrhage was identified. Histological examination confirmed the existence of chromophobe adenoma and, furthermore, immunohistochemical study revealed the existence of a prolactinoma. The size of the tumor gradually diminished with the administration of bromocriptine, and serum prolactin levels returned to normal value during the postoperative course. Among all cases of prolactinomas reported in previous medical literature only 23 cases of patients under 20 years old have been reported. The authors analysed our case of prolactinoma along with other infrequent cases where intratumoral hemorrhage was especially noticeable. PMID- 8474594 TI - [Cavernous angioma in the cerebellopontine angle: a case report]. AB - A rare case of cavernous angioma (CA) in the cerebellopontine angle (CPA) is reported. A 60-year-old female suffered from a right progressive sensorineural hearing loss and a successive right facial paresis over 2 years. A small mass was detected in her right CPA on CT scans. Both T1- and T2-weighted MR images demonstrated an intracanalicular lesion protruding into the CPA as being hyperintense. A small red colored lobulated tumor involving the 7th and 8th cranial nerves was found in the CPA through the suboccipital approach. The tumor contained multiple small hematomas in various stages. Biopsy with evacuation of these hematomas was selected to avoid damaging the cranial nerves. Histological examination of the specimen disclosed it as CA. Postoperatively her facial paresis improved slightly, but her hearing loss remained unchanged. Discussions were carried out concerning clinical and neuroradiological features of CA in the internal auditory canal and CPA. The present case and a previously reported 17 cases were the subjects under discussion. PMID- 8474595 TI - [A case of penetrating head injury caused by nail-gun]. AB - A rare case of penetrating head injury caused by a nail-gun was described. A 24 year-old male was admitted to our hospital due to head injury. He had handled a nail-gun at a construction site. On admission the patient was fully conscious with no neurological defects. A small wound was observed at the left front temporal region. Skull films showed a large nail embedded in the skull cavity. A computed tomographic (CT) scan, changing level of window, demonstrated intracerebral hematoma, fragment of skull bone and nail. Cerebral angiography (CAG) showed extravasation at the left frontal region. Emergency operation was performed and his recovery was uneventful. Twenty-two craniocerebral injuries caused by nail-guns have been reported in world medical literature but this was the first report in Japan. The characteristics of craniocerebral nail-gun injuries were less damage and better prognosis compared with gunshot injuries. However intracranial infection and vascular injury were possible lethal complications. In this case, preoperative examination, such as CT scan and CAG was valuable and the early operation for the sake of safety was very effective. PMID- 8474596 TI - Third international symposium on amyotrophic lateral sclerosis/motor neuron disease (Solihull, Birmingham, England. November 2-4 1992). PMID- 8474597 TI - Early central nervous system changes in human immunodeficiency virus (HIV) infection. AB - Early HIV infection of the CNS, as demonstrated by cerebrospinal fluid studies, seems relatively common. However most HIV carriers remain neurologically unimpaired during the incubation period. A few psychometric, radiological, and electrophysiological studies suggest that neurological abnormalities are present at early stages of HIV infection; the findings of these studies are controversial and until recently, they have not been supported by neuropathological data. Early brain changes, including leptomeningitis and vasculitis with myelin pallor and gliosis of the deep white matter are probably secondary to vascular inflammation and opening of the blood-brain barrier. Such conclusions are drawn from the examination of brains of asymptomatic HIV-positive individuals who died from unnatural causes, and of rare cases with acute fatal encephalopathy revealing HIV infection. In addition, early experimental simian immunodeficiency virus infection and feline immunodeficiency virus encephalopathy have demonstrated similar changes to those in man. Although small amounts of viral genome were detected by PCR in a few cases, the early changes in the human brain do not seem to result from a productive HIV infection of the CNS, as seen in HIV encephalitis. The occurrence of a usually asymptomatic and transient immunopathological reaction coinciding with early HIV infection of the nervous system appears to be more likely. PMID- 8474598 TI - Blood-nerve barrier: ultrastructural and endothelial surface charge alterations following nerve crush. AB - Nerve crush results in an enhanced vascular permeability of the endoneurial vessels distal to the lesion. Vascular permeability at the blood-nerve barrier (BNB) to serum proteins is influenced by many factors, including anionic surface charge, endothelial vesicular transcytosis and the presence or absence of fenestrated vessels. Using mice and rats, the present ultrastructural investigation examined the effect of nerve crush (axonotmesis) on: (1) the distribution of endothelial anionic sites and (2) the appearance of fenestrations in endoneurial vessels after 4 and 14 day intervals as demonstrated with cationic probes. Transient anionic fenestrations developed in a minority of mouse endoneurial vessels in 4-day crushed nerves, but were not found in 14-day crushed nerves of mice nor in crushed nerves of rats. The known increase in the permeability of endoneurial vessels in rats and mice was not associated with reduced luminal labelling with cationic ferritin at physiological pH. At pH 2.0 the labelling of glycocalyx moieties (such as sialic acid) with cationic colloidal gold was disrupted in some epi- and endoneurial vessels of 4-day rats, but in a greater proportion after 14 days. The enhanced permeability of the BNB during degeneration and regeneration is related to the formation of anionic fenestrations in endoneurial vessels of mice and to the reduced and uneven distribution of endothelial glycocalyx moieties that are anionic at pH 2.0 in rats. PMID- 8474600 TI - Adaptation of tibial nerve myelinated fibre parameters to reduced limb length caused by irradiation. AB - Irradiation of a rat hind limb at 15 days of age caused marked shortening of the limb, with a consequent reduction in nerve length. The tibial nerves of the irradiated limbs were examined qualitatively and quantitatively, and compared with the unirradiated nerve. There was no evidence of fibre degeneration and only very occasional myelin abnormalities. Myelinated fibre numbers were very slightly reduced, possibly due to irradiation effects on small myelinated fibres. Internodal lengths were reduced in proportion to limb length. Mean axon diameters were slightly increased, and myelin sheath thickness reduced. This experimental model provides a new method of altering nerve fibre parameters without surgical intervention. PMID- 8474599 TI - Progressive degeneration of motor nerve terminals in GAD mutant mouse with hereditary sensory axonopathy. AB - The evolution of motor nerve degeneration was examined in gracile axonal dystrophy (GAD) mutant mice, which develop initial sensory ataxia and subsequent motor paresis. Using the anterior gracilis (AG) muscle, which is innervated at two discrete and well-separated endplate zones, we demonstrated that axonal degeneration occurred first at motor nerve terminals in the distal endplate zone, and then extended gradually from the distal to the more proximal parts of affected axons in the intra-muscular nerve trunk. In contrast to the degeneration in the distal zone, active degeneration was less marked in the proximal endplate zone and, furthermore, most terminal axons had begun to produce regenerating sprouts. Ventral horn cells were histologically normal, even at advanced stages. These results indicate that, as previously observed in sensory nerves, dying back degeneration progresses later in the lower motor neuron system, even within one muscle. The mechanism(s) influencing the activation of axonal regeneration are discussed. This mutant mouse will be a useful model for the study of regenerating phenomena in dying back degeneration of genetically compromised motor neurons, as well as for the study of the pathogenesis of hereditary sensory and motor neuropathies in man. PMID- 8474601 TI - Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat. AB - The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death. PMID- 8474602 TI - Neural tube defects in the parietal region of human embryos: failure to close or closure-reopening? AB - This is a follow-up study to earlier investigations on neural tube defects (NTD) in the Kyoto collection of human embryos. It includes an extensive examination of abnormal embryos which have been photographed and serially sectioned following routine histological preparation. Two new types of NTD are described in the parietal region (the roof of the third ventricle) which had previously been overlooked. These anomalies were found most commonly in embryos at the developmental period. Carnegie stage [CS] 16-23 (embryonic days 38-52). Hypotheses are advanced regarding the genesis of NTD and whether encephaloceles and NTD are part of a spectrum of malformation. This study also reinforces evidence that the occurrence of NTD is significantly higher in the embryonic period than at birth. Animal studies, using the guinea-pig are discussed with regard to the investigation of hypotheses put forward to explain the genesis of NTD. PMID- 8474603 TI - A four-layered 'lissencephalic' cortex induced by prenatal X-irradiation in the rat. AB - A four-layered cortex is produced in the dorsal region of the rat brain, after 200 cGy X-irradiation at embryonic day 16. The layer 1 is the molecular layer; layer 2 is the upper cellular layer which is in continuity with normal layers V and VI in the lateral cortex; layer 3 is a sparsely cellular layer; and layer 4 is the inner cellular layer which is composed of neurons normally committed to the upper cortical layers. This failure of neuroblast migration to the upper layers is associated with reduced numbers, and morphological abnormalities, of radial glial cells in the dorsal cortex. This further supports the idea that abnormal interactions between neuroblasts and radial glial cells result in abnormal migratory patterns. Since a similar four-layered organization is found in human lissencephaly type I, the present results bring new data that can serve our better understanding of human cortical malformations. PMID- 8474604 TI - Zn-binding globulin in human fetal brain and liver: a marker for passive blood/CSF transfer of protein. AB - The presence of Zn-binding globulin (ZnbG) during human fetal development was studied in cerebrospinal fluid (CSF) and plasma with immunodiffusion methods and in brain, CSF, plasma and liver using immunocytochemical methods. At the earliest stages examined with immunocytochemistry (5-6 weeks gestation) no staining for ZnbG was visible in liver, plasma, CSF or brain. However, the primitive mesenchyme exhibited a prominent staining reaction. In late embryonic and early fetal stages, staining for the protein was most prominent in the spinal cord, brain stem and diencephalon and in the choroid plexuses and marginal and subplate zones in the telencephalon. At the cellular level, synaptic strata and territories were most strongly stained. The distribution of ZnbG in the early developing central nervous system suggests that this protein may be involved in the initial establishment of CNS circuitry. Embryonic brain was positive for ZnbG well before the protein could be detected in CSF, plasma or liver. The early occurrence of ZnbG in brain tissue prior to its presence in liver or plasma also suggests that the protein is synthesized in early fetal brain. At the time when CSF first became positive (17 weeks gestation), the brain staining had largely disappeared. ZnbG in plasma increased throughout gestation to reach 2.6 +/- 0.4 mg/100 ml at term and subsequently increased to an adult value of 6.8 +/- 1.5 mg/100 ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474605 TI - Brown-Vialetto-Van Laere syndrome. AB - The clinical and pathological findings of a male with the Brown-Vialetto-Van Laere syndrome are described. This rare and fatal affection of the nervous system involves mainly the brain stem with the prominent and early manifestation of sensorineural deafness. Increased awareness and documentation of this disorder has added information on the mode of inheritance. PMID- 8474606 TI - Neurocytoma/lipoma (neurolipocytoma) of the cerebellum. AB - We describe a unique tumour that was removed from the posterior fossa of a woman aged 50 years. It was characterized histologically by bland, oval cells with fibrillary cytoplasm and by small groups of lipocytes. Immunocytochemical studies demonstrated expression of synaptophysin, neuron specific enolase and PGP 9.5, but a few cells also expressed glial fibrillary acidic protein and desmin. The combination of neuroectodermal and mesodermal features in this tumour is discussed in relation to primitive neuroectodermal tumours and neurocytoma. PMID- 8474607 TI - Electroencephalographic and neuroimaging findings in neonates undergoing extracorporeal membrane oxygenation. AB - Electroencephalograms (EEGs) were recorded on 36 infants who were treated with arteriovenous extracorporeal membrane oxygenation (ECMO) between 1986 and 1989. Twelve of 36 infants had EEGs prior to and during ECMO. Twenty-one infants who met ECMO criteria but were treated with mechanical ventilation only served as a comparison (COMP) group. Electrographic seizures occurred in 7 of the 36 (19%) ECMO patients and in 3 of the 21 (14%) COMP patients. Five of 7 ECMO infants had electrographic status epilepticus. Three infants developed electrographic seizures during ECMO in association with an acute cerebral injury. These patients did not have significant hemispheric predominance in the origin of electrographic seizures (2 right, 3 left and 2 bilateral). Repetitive or periodic discharges (RPD) with frequencies between 0.5 and 5 Hz were seen after starting therapy in 23 of the 36 (64%) ECMO patients and 15 of the 21 (71%) of the COMP group. Only in the ECMO patients did RPD arise significantly more frequently from the right hemisphere (13 right, 4 left and 6 bilateral; p = 0.015). Neuroimaging studies showed evidence of ischemic lesion in 8 of the 36 (22%) ECMO patients with significantly right-sided predominance (5 right, 1 left and 2 bilateral; p = .05). Cerebellar hemorrhages occurred in 3 ECMO patients. Ischemic lesions occurred in 3 of the 21 (14%) COMP patients, all occurring on the left side. In the ECMO group, severe outcome or death was significantly associated with the presence of electrographic seizures, status epilepticus, and suppression-burst pattern (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474608 TI - Effect of the hypoxanthine/xanthine oxidase system on dopamine outflow from rat striatal synaptosomes. AB - The effect of the oxygen radical generating system, hypoxanthine/xanthine oxidase (Hx/XOD), on the spontaneous and potassium-stimulated outflow of the neurotransmitter dopamine (DA) from rat striatal synaptosomes was studied. The efficacy of some radical scavengers was also tested. DA outflow was measured by incubation of [3H]-DA prelabeled synaptosomes (P2) in Krebs-Ringer buffer, containing either normal or depolarizing K+ concentrations. The reactions were terminated by filtration of the synaptosomes through Sartorius filters. Hx/XOD increased the spontaneous DA outflow in a dose and time dependent manner. The reduction found in synaptosomal DA content could be explained by disturbances of DA uptake or reuptake. The K+ stimulated outflow was not altered by the lower doses of Hx/XOD, whereas, when very high doses of Hx/XOD were used, the K+ stimulated DA outflow was decreased. High doses of Hx/XOD may deplete the synaptosomal DA releasable pool, leaving little DA available for extra-stimulated outflow by high concentrations of K+. The K(+)-stimulated outflow of DA is a less sensitive process against radical attack than the spontaneous release of DA. A protective action of catalase, but no effect of superoxide dismutase was demonstrated in these experiments. PMID- 8474609 TI - Ultrasound measurement of quadriceps muscle in the first year of life. Normal values and application to spinal muscular atrophy. AB - Using real-time ultrasound imaging normal values were obtained for quadriceps muscle thickness and subcutaneous tissue depth in the first year of life from 120 normal infants. These values were corrected for weight and height by introduction of a "correcting factor". In addition, a "modified muscle index" was calculated by multiplying the ratio of muscle to subcutaneous tissue thickness with the correcting factor and showed a steady increase from birth (mean 2.1) to the end of the first year (mean 4.8). The study of 12 patients with spinal muscular atrophy type I (SMA I) revealed that 9 out of 12 SMA I patients failed to reach the 3rd percentile for the muscle to subcutaneous tissue ratio and 10 out of 12 were well below the 3rd percentile for the modified muscle index due to their muscle atrophy. Only the two youngest SMA I patients aged 4 and 6 weeks reached values on the 3rd percentile. In contrast, 10 patients with myopathy and one patient with holoprosencephaly showed values within the normal percentiles even in the presence of severe clinical muscle weakness and signs of atrophy on muscle histology. In the differential diagnosis of early onset myopathy, atrophy of the quadriceps muscle during the first months of life in the absence of markedly increased echodensity seems to be a pathognomonic finding for SMA. PMID- 8474610 TI - MRI of the head in the evaluation of microcephaly. AB - Fifty-five patients with microcephaly (head circumference < -2SD) were identified. The 55 patients were divided into two groups, consisting of group 1 (34 cases) in which genetic causes were considered primary, and group 2 (21 cases) in which intrauterine and/or postnatal acquired factors were thought to be responsible. MRI abnormalities were present in 80% of the total series: 68 and 100% in groups 1 and 2, respectively. In group 1, migration abnormalities were the most prominent and mental retardation was the major neurological handicap, while in group 2, hydranencephaly and infarction secondary to brain circulatory derangements were the most frequently observed abnormalities, with severe multiple handicaps such as cerebral palsy, epilepsy and mental retardation seen. Head MRI was considered indispensable in the investigation of the causes of microcephaly and in determining the neurological prognosis of affected patients. PMID- 8474611 TI - Regional cerebral blood-flow measured by HMPAO and SPECT in a 5-year-old boy with Landau-Kleffner syndrome. AB - We present a 5-year-old boy with Landau-Kleffner syndrome, whose clinical manifestations were very similar to cases previously reported in the literature. CT and MRI scan failed to document any morphological abnormalities of his brain. However, high resolution rCBF imaging by HMPAO and SPECT demonstrated relatively low-flow areas in the left middle frontal gyrus and the right mesiotemporal/hippocampal region corresponding to the localization of EEG changes. PMID- 8474612 TI - Carbohydrate-deficient glycoprotein (CDG) syndrome--a new variant, type III. PMID- 8474613 TI - Functional hemispherectomy in children. AB - Functional hemispherectomy, indicated for the control of pharmacologically refractory seizures, has been used at the Montreal Neurological Hospital since 1974. We have used this technique in 18 children suffering from intractable seizures secondary to conditions such as infantile hemiplegia, chronic encephalitis, head trauma, cerebrovascular accident, brain dysplasia and Sturge Weber angiomatosis. None has developed superficial cerebral hemosiderosis often seen following the classical anatomical hemispherectomy. Eighty-two per cent (82%) of patients have been seizure-free since hospital discharge while another 11.5% have had at least 80% reduction in their seizure frequency. Most patients have shown an improvement in their intellectual capacity and sociability. PMID- 8474614 TI - Sex differences in the maturation of sleep/wake patterns in high risk for SIDS infants. AB - Male and female high risk for SIDS infants were compared with a group of rigorously matched controls in sleep/wake variables during the peak period for SIDS, i.e., 2-4 mos. Continuous 24-72 hr. in-hospital recordings yielded data based on 3,792 hrs. of electrophysiological activity. The data show that risk male infants fail to demonstrate an increase in wakefulness with age and reveal a lag in the maturation of REM sleep compared to controls and female risk infants during the critical age for SIDS. Significant sex differences within the first six months of life are of particular importance because of the consistently reported higher incidence of SIDS in males than females. An immature sleep/wake organization which occurs differentially in male high risk for SIDS infants suggests that a CNS functional disorder is present selectively in male infants as a precursor to SIDS. The greater susceptibility of male infants to SIDS emphasizes the importance of these data based on unique long-term recordings. PMID- 8474615 TI - Stereoselective actions of the isomers of metitepine at 5-HT1D receptors in the guinea pig brain. AB - The present studies examined the relative antagonist potencies of the optical isomers of the 5-HT receptor antagonist metitepine at the 5-HT1D binding site labelled by the novel radioligand serotonin-O-carboxymethylglycyl [125]iodotyrosinamide ([125I]GTI), and at the terminal 5-HT autoreceptor in guinea pig frontal cortex, a proposed model of 5-HT1D receptor activation. The pharmacological specificity of the [125I]GTI binding site in guinea pig frontal cortex was similar to previously published studies in the bovine cortical 5-HT1D recognition site labelled with [3H]5-HT. The (+) isomer of metitepine displaced [125I]GTI binding with a lower affinity (64 nM) than did the (-) isomer (18 nM), which was equiactive with the racemic mixture. The (-) isomer of metitepine was more effective than the (+) isomer at attenuating the inhibitory effects of 5-HT and sumatriptan at the guinea pig terminal 5-HT autoreceptor; the apparent pA2 of the (-) isomer was 8.0 (sumatriptan) and 7.7 (5-HT) while the apparent pA2 of the (+) isomer was 7.1 (sumatriptan) and 6.8 (5-HT). The (-) isomer was more effective than the (+) isomer at enhancing stimulated [3H]5-HT release. These findings support the identification of the guinea pig 5-HT terminal autoreceptor as a 5-HT1D receptor and reinforce the species homology between the 5-HT1B and 5 HT1D receptors. PMID- 8474616 TI - Brainstem serotonin receptors in the guinea pig: implications for myoclonus. AB - The brainstem is the locus of serotonin (5-HT)-mediated myoclonus in the guinea pig, which is induced by 5-hydroxy-L-tryptophan (L-5-HTP) and indole but not piperazine 5-HT receptor agonists. As an initial step in testing the hypothesis that one 5-HT receptor subtype mediates this effect, we measured seven 5-HT receptor binding sites and the 5-HT uptake site in guinea pig brainstem and compared them to the rat. In guinea pig brainstem, the rank order of binding site density was: 5-HT transporter site >> 5-HT1D > antagonist-labeled 5-HT2 > 5-HT1A, 5-HT1C > 5-HT1E > agonist-labeled 5-HT2 binding site. There were fewer 5-HT1A and 5-HT1C binding sites and 5-HT uptake sites in guinea pig than rat brainstem, more 5-HT1D and antagonist-labeled 5-HT2 sites, but the differences were 2-fold or less. The major species difference was that 5-HT1B sites were virtually undetectable in guinea pig brainstem. Limited competition experiments with related 5-HT receptor subtype-selective agonists and antagonists suggested that the sites in guinea pig brainstem conformed to those described in the rat. 5-HT agonist and antagonist dose-threshold and dose maximum-effect data from guinea pig myoclonus in vivo were compared with receptor affinities at each receptor site in vitro from the literature. No convincing correlation between myoclonus and one particular 5-HT site was found. These data indicate the presence of a full complement of 5-HT receptor binding site subtypes in guinea pig brainstem with some species differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474617 TI - Social interaction and elevated plus-maze tests: changes in release and uptake of 5-HT and GABA. AB - Changes in release and uptake of [3H]5-HT and [14C]GABA were compared in slices taken from the hippocampus and frontal cortex of rats, left undisturbed in their home-cages, or exposed for 5 min to the elevated plus-maze or social interaction tests of anxiety. Exposure to the plus-maze decreased cortical GABA function (shown by decreased release) and increased hippocampal 5-HT function (shown by increased K(+)-evoked release but more markedly by decreased uptake). Compared with undisturbed home cage controls, only the high light, familiar condition of the social interaction test resulted in a significant increase in K(+)-evoked release of both [3H]5-HT and [14C]GABA from the hippocampus. All four social interaction test conditions resulted in increases in cortical uptake of [3H]5-HT and all but the high light, unfamiliar condition increased cortical uptake of [14C]GABA. Analysing the two factors manipulated in the social interaction test, unfamiliarity with the test arena resulted in increased uptake of hippocampal [3H]5-HT and decreased cortical [14C]GABA, whereas an increase in the level of light decreased the cortical uptake of [14C]GABA. The results show that changes in presynaptic function occur rapidly in response to a brief exposure to animal tests of anxiety. However, only the increased hippocampal release of 5-HT is likely to be causally linked to anxiety and the results show that this cannot be the sole explanation. PMID- 8474618 TI - Subchronic treatment with morphine inhibits the hypertension induced by isolation stress in the rat. AB - As preliminary evidence for the implication of opioids in the increase in blood pressure due to the stress of brief social deprivation, hypertension has been shown to be antagonized by acute administration of opiate receptor blockers. As a further evidence of involvement of opioids in the hypertensive response to this type of stress, cross-tolerance ought to be capable of being demonstrated in isolated animals, treated with an opiate. When rats were treated subchronically with morphine in the drinking water throughout the isolation period (1-15 days), readings of blood pressure did not show any variation, as compared to group housed control rats. However, 7 days after withdrawal of morphine readings of arterial pressure in the isolated rats increased above the levels of the group housed control animals. These findings support the idea that an endogenous opioid system is implicated in the induction of readings of high blood pressure due to the stress of social deprivation. PMID- 8474619 TI - Effect of stobadine on lipid peroxidation and phospholipids in rabbit spinal cord after ischaemia. AB - Stobadine, a drug with the pyridoindol structure, was compared with thiopental and pentobarbital for its ability to inhibit stimulated peroxidation in homogenates of spinal cord in vitro. The antioxidative capacity of the drug exceeded that of barbiturates more than 100-fold. Stobadine was also shown to inhibit the increase in formation of TBA-RS in homogenates of rabbit spinal cord, subjected to 20 min ischaemia, to the level comparable with controls. Administration of the drug (6 mg kg-1) to animals 5 min before 20 min ischaemia had no effect on level of lipid peroxidation products in the spinal cord; however, it slowed down stimulated Fe(2+)-dependent peroxidation after in vitro incubation of the homogenates and increased the concentration of phosphatidylserine and ethanolamine plasmalogens, as compared with non-treated animals. Application of stobadine 2 min before the release of an aortic occlusion increased the antiradical capacity in homogenates of spinal cord and revealed an ameliorating effect on the composition of phospholipids. PMID- 8474620 TI - Effect of 4-phenyl-1,2,3,4-tetrahydroisoquinoline on ambulation induced by injection of methamphetamine into the nucleus accumbens in rats. AB - 4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) has previously been shown to have antagonistic properties to methamphetamine in the spinal cord. Administration of 4-PTIQ (5 mg/kg, s.c.) reduced the ambulation induced by methamphetamine (0.5 mg/kg, s.c.) in rats. Methamphetamine (3 micrograms), injected unilaterally into the nucleus accumbens, increased ambulation. Alone, 4 PTIQ (10 micrograms) failed to elicit ambulation; however, it inhibited the methamphetamine-induced increase in ambulation. The alpha 1-antagonist prazosin (0.5 micrograms) or the beta-antagonist propranolol (3 micrograms) showed no effect on ambulation induced by methamphetamine. Haloperidol (5 ng), which possesses strong dopamine-blocking activity, abolished the ambulation induced by methamphetamine. The drug 4-PTIQ had weak affinity for dopamine D1 and D2 receptors. These results support the possibility that the inhibitory effects of 4 PTIQ on the ambulation-stimulating effects of methamphetamine, are due to blocking of the dopamine-releasing effect of methamphetamine but not due to dopamine blocking effects. PMID- 8474621 TI - Protective effect of flunarizine and nifedipine alone and in combination with anticonvulsant drugs against PTZ-induced seizures in mice. AB - The anticonvulsant effect of flunarizine has been compared to that of nifedipine in the pentylenetetrazole (PTZ)-induced seizure incidence/latency test and the PTZ seizure threshold test in mice. Nifedipine was found to have anticonvulsant activity in both models but flunarizine only had an anticonvulsant effect in the PTZ seizure incidence/latency test. Interactions with commonly used anti epileptic drugs were also examined. In both models, the anticonvulsant effects of small doses or carbamazepine and phenytoin were enhanced by flunarizine and the effects of small doses of ethosuximide were enhanced by nifedipine. The effects of large doses of the anti-epileptic drugs were not further enhanced by either flunarizine or nifedipine. It is possible that these findings in mice are relevant to the variability of the responses to calcium antagonists as add-on therapy for epilepsy in man. PMID- 8474622 TI - Effects of acute and subchronic administration of ritanserin on the social behaviour of mice. AB - The effects of ritanserin on the behaviour of adult male CD1 mice were examined after acute intraperitoneal injection (0.1, 0.3 and 0.6 mg/kg) and after administration for 12-15 days in the drinking fluid at 1.6 mg/l (0.32 mg/kg daily) and 3.1 mg/l (0.7 mg/kg daily). The behaviour of each mouse was examined by ethological procedures during 5 min social encounters with an untreated partner in an aversive situation, an unfamiliar neutral cage, and in a familiar situation, the animal's home cage. Behaviour also was monitored for 5 min in the light-dark box. In the acute studies, behavioural observations commenced at 30 min after injection. In the home cage, ritanserin significantly increased social investigation during social encounters and reduced exploratory activity at all doses tested, after both acute and subchronic administration. In the neutral cage, acutely administered ritanserin increased social investigation and reduced non-social activity at all dose levels. Effects were maximal at 0.3 mg/kg, and at this dose it also increased aggression. In the neutral cage after subchronic administration, ritanserin at both dose levels increased aggression, digging and investigation of the substrate and occurrence of the social act, "attend", while reducing the time spent in non-social exploration. Ritanserin did not affect behaviour in the light-dark box. The significance of these findings relative to the anxiolytic and antidepressant effects of ritanserin is discussed. PMID- 8474623 TI - Partial 6-hydroxydopamine-induced lesions and haloperidol-induced catalepsy. AB - Rats with partial (36%) 6-hydroxydopamine-induced lesions of the striatal dopamine system or sham-lesioned controls were tested for duration of catalepsy after 1.0, 2.0 and 4.0 mg/kg haloperidol. Thereafter, half of each group was given haloperidol (2.0 mg/kg) chronically for 84 days. The cataleptic responses to the 3 doses were tested again on days 13-15 and 74-76 of the chronic injections. Animals that were lesioned and treated with haloperidol chronically had longer durations of catalepsy at the first two dose-response determinations. At the third dose-response determination, there were no differences among the 4 groups. Additionally, all groups displayed an increase in duration of catalepsy at the second and third dose-response determinations, relative to the first. The increase in haloperidol-induced duration of catalepsy in the lesioned group suggests that lower levels of dopamine in the striatum may potentiate extrapyramidal side-effects. PMID- 8474624 TI - Responses of neurons in bed nucleus of the stria terminalis to microiontophoretically applied morphine, norepinephrine and acetylcholine. AB - The bed nucleus of the stria terminalis is a basal forebrain nucleus that receives inputs from limbic system nuclei and sends projections to several hypothalamic and brainstem nuclei, proposed to be involved in the physiological response to stressors. The bed nucleus of the stria terminalis also receives norepinephrine- (NE), acetylcholine- (ACh) and opiate-containing projections. The objectives of this experiment were to examine the effects of microiontophoretically applied ACh, NE and morphine sulfate (M) on neurons of the bed nucleus in urethane-anesthetized rats and to determine the degree to which these systems interact on individual neurons. Acetylcholine was excitatory in 43% of the neurons and NE was inhibitory in 70%. Morphine however, elicited two distinct types of response--excitation in 24% of the neurons and inhibition in 28%. Each of these effects was current-dependent and monophasic. Since 77% of neurons of the bed nucleus responded to two or more of the drugs used in this experiment, statistical analysis was used to determine correlations between responses to each of these drugs. This analysis showed that neurons that responded to M with excitation also responded to ACh with excitation, while neurons that responded to M with inhibition, were nonresponsive to ACh. No correlation was found between NE and either M or ACh. Thus, this experiment demonstrated the possible effects of noradrenergic, cholinergic and opioid innervation on firing rates of neurons of the bed nucleus of the stria terminalis and may explain the roles these neurotransmitters play in modulating the response to stress. PMID- 8474625 TI - Calcium-dependent release of norepinephrine from permeabilized PC12 cells is inhibited by approximately 48 and approximately 112 kDa fragments of botulinum neurotoxin type E. AB - Permeabilized PC12 cells exhibit a Ca(2+)-stimulated norepinephrine secretory pathway which is sensitive to botulinum neurotoxin serotypes A, B and E [Lomneth R., Martin T.F.J. and DasGupta B. R. (1991) J. Neurochem. 57: 1413-1421]. Two novel amino terminal fragments of the 150 kDa neurotoxin serotype E (approximately 112 and 48 kDa), produced by digestion with pepsin, were tested in permeabilized PC12 cells. The intracellular inhibitory activity of the approximately 112 kDa amino terminal fragment, like that of the 150 kDa neurotoxin, was progressively enhanced after trypsinization and dithiothreitol reduction. The approximately 50 kDa C-terminal half of the heavy chain therefore does not contribute to the enhancement of inhibitory activity. The approximately 48 kDa amino terminal light chain-like fragment completely inhibited release of norepinephrine, with an IC50 = 500 pM (more potent than the light chain isolated after digestion with trypsin) not requiring reduction with dithiothreitol. These results clarify the molecular basis of activation of neurotoxin by trypsin and dithiothreitol. PMID- 8474626 TI - Cholinesterase inhibitor effects on extracellular acetylcholine in rat striatum. AB - The effects of inhibition of cholinesterase on levels of extracellular acetylcholine in the striatum of freely moving rats, were investigated with a microdialysis technique. Acetylcholine could not be detected under basal conditions. However, local administration of the cholinesterase inhibitors neostigmine, physostigmine or heptyl-physostigmine through the dialysis probe elevated acetylcholine above the detection limit. Complex interactions between the effects of local and systemic cholinesterase inhibitors were observed. Whereas systemic administration of physostigmine or heptylphysostigmine alone increased the extracellular concentration of acetylcholine, they also caused acetylcholine to fall below baseline levels, which had been established by perfusing physostigmine through the microdialysis probe. These studies demonstrate the ability of local inhibition of cholinesterase to affect the observation of effects of systemically-administered drugs. PMID- 8474627 TI - Synergism between the antinociceptive effects of intrathecal midazolam and fentanyl on both A delta and C somatosympathetic reflexes. AB - The interaction between the antinociceptive effects of fentanyl and midazolam, administered intrathecally (i.t.), was examined in dogs. Midazolam 1 mg (i.t) depressed the A delta and C fibre mediated somatosympathetic reflexes to 68.3 and 85.2% of control values and then reduced the subsequent doses of fentanyl (i.t.) required to abolish these reflexes by 50%. After midazolam (1 mg, i.t.) the ED values for fentanyl were markedly less than the theoretical predicted additive values. This indicates synergism between the effects of fentanyl and midazolam. PMID- 8474629 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 8474628 TI - Effects of indeloxazine on hippocampal CA1 pyramidal cell damage following transient cerebral ischemia in the gerbil. AB - The effects of indeloxazine on the ischemia-induced death of hippocampal CA1 pyramidal cells following transient cerebral ischemia were examined in the mongolian gerbil. Increased survival of CA1 pyramidal cells was demonstrated in animals pre- and post-treated with indeloxazine. Increased survival of CA1 pyramidal cells was, however, not demonstrated in animals post-treated but not pre-treated with indeloxazine. A previous study has demonstrated that indeloxazine increases the glucose and adenosine triphosphate (ATP) contents in the brain probably through an enhanced capability of oxidative phosphorylation. It has been reported that increases in the glucose and ATP contents in the brain before ischemia delay the onset of massive ionic fluxes during ischemia. The delay in onset of this ionic event may help to protect these cells from death. The present data suggest that energy state before ischemia may play an important role in the protective effect of indeloxazine. PMID- 8474630 TI - Influence of oxytocin on nociception and morphine antinociception. AB - In the hot plate test the intracerebroventricular (i.c.v.) injection of oxytocin produced a significant decrease in nociception, starting from the dose of 1 microgram/rat. A comparable effect was obtained with 10-200 times higher intraperitoneal (i.p.) doses. The i.c.v. injection of the oxytocin antagonist d(CH2)5-Tyr(Me)-[Orn8]-vasotocin, while having no influence per se, completely prevented the antinociceptive effect of an equal i.c.v. dose of oxytocin. The antinociceptive effect of oxytocin was also prevented by naltrexone, and oxytocin caused a small but significant increase of the antinociceptive effect of morphine and of its duration. These data indicate that pharmacological amounts of oxytocin produce antinociception, that occurs through the activation of oxytocin receptors; endogenous opioid systems seem to be involved altogether. PMID- 8474631 TI - Characterization of the release and metabolism of delta sleep-inducing peptide (DSIP) in the rat brain. AB - In the present study, we examined whether delta sleep-inducing peptide (DSIP) was (1) secreted from neurons on depolarization and (2) degraded by membrane associated peptidases. Incubation of DSIP with rat brain membrane resulted in the degradation of DSIP with liberation of tryptophan, an N-terminal amino acid of DSIP. Bestatin and puromycin, aminopeptidase inhibitors, significantly inhibited the degradation of DSIP and release of tryptophan. The releases of immunoreactive DSIP-like substance (irDSIP) from rat brain slices and synaptosomes were significantly stimulated by high K(+)-evoked depolarization. The released irDSIP was coeluted with native DSIP on gel filtration chromatography. High K(+)-evoked release of irDSIP did not show extracellular Ca(2+)-dependency. This Ca(2+) independency suggests that the secretory pathway of DSIP may be different from that of other neurotransmitters. These results demonstrate that DSIP is released from nerve endings on depolarization and inactivated by membrane-associated puromycin-sensitive aminopeptidase. Therefore, DSIP may serve as a neuropeptide like material in the central nervous systems. PMID- 8474632 TI - Increased release of immunoreactive CCK-8 by electroacupuncture and enhancement of electroacupuncture analgesia by CCK-B antagonist in rat spinal cord. AB - Cholecystokinin octapeptide (CCK-8) in CNS has been shown to function as a neuropeptide with potent anti-opioid activity. It hinders opioid analgesia and facilitates opioid tolerance. The present study showed that electroacupuncture (EA) stimulation produced a marked increase of the CCK-8 immunoreactivity (ir) in the perfusate of the rat spinal cord. The increase of CCK-8-ir was most marked in response to EA of 100 Hz and 15 Hz, and less marked in response to EA of 2 Hz. Since CCK-8 has been shown to possess potent anti-opioid activity at the spinal level, blockade of the spinal CCK effect would be expected to potentiate EA induced analgesia which is known to be opioid-mediated. Intrathecal (i.t.) administration of CCK-B antagonist L-365,260 per se did not affect tail flick latency (TFL) to any significant extent, yet it potentiated EA induced analgesia in a dose- and frequency-dependent manner. The potentiation was most marked at a dose range of 2.5-5.0 ng (i.t.) and at a frequency rank order of 100 Hz > 15 Hz > 2 Hz. The results suggest that an increased release of CCK-8 following EA may limit the effect of opioid peptides, and that the CCK-B receptor mediates the anti-opioid effect of CCK-8 in rat spinal cord. PMID- 8474633 TI - Evidence for a role of noradrenergic neurons in the increase in concentration of preprocholecystokinin-mRNA after cerebral cortex injury in rats. AB - A knife cut injuring the meninges and the upper layers of rat neocortex transiently increases the levels of preprocholecystokinin-mRNA in the whole ipsilateral cortex. 48 h after the injury, the rise in gene expression was reduced by the edema-induced increase in tissue pressure which develops after the trauma. The beta-adrenoceptor antagonists alprenolol (4 mg/kg) and propranolol (1 mg/kg), given i.m. 30 min prior to the injury, reduced the increase by 75.6 and 100%, respectively. In contrast, blockade of alpha-adrenoceptors as well as of dopamine and serotonin receptors by respective antagonists did not affect the injury-induced increase in levels of preprocholecystokinin-mRNA. These results suggest that noradrenergic neurons can contribute via stimulation of beta adrenoceptors to the initiation of the injury-induced increase in preprocholecystokinin gene expression. PMID- 8474634 TI - Effects of calcitonin gene-related peptide on the rabbit electroretinogram. AB - In order to better understand the role of Calcitonin gene-related peptide (CGRP) in mammalian retina, the dose related effects of human CGRP (hCGRP) on rabbit electroretinogram (ERG) were examined in the present study. CGRP was administered intraocularly in doses of 0.1, 1.0 and 10.0 micrograms. ERG A- and B-wave as well as oscillatory potentials (P1, P2, P3 and P4) were recorded. The highest dose of CGRP (10.0 micrograms) significantly increased the amplitudes of the A-wave and OP components (P1, P2, P3 and P4) produced by relatively high stimulus intensity. The same dose of the peptide also enhanced B-wave amplitude at all intensities studied. The effects of the intermediate dose of CGRP (1.0 microgram) on the B wave amplitudes were dependent on stimulus intensities. B-wave amplitudes at high stimulus intensities were not affected by 1.0 microgram of CGRP but were significantly increased with relatively lower stimulus intensities. The amplitudes of P3, one of OP components, were significantly increased. However, amplitudes of A-wave and other OP components (P1, P2 and P4) were not affected by 1.0 microgram CGRP. The lowest dose of the peptide (0.1 microgram) did not affect any amplitudes of ERG components. Implicit times of A-wave, B-wave and OP components were not significantly affected by the different doses of CGRP. Taken together, these results indicate that CGRP may play a functional role in modulating retinal responses to photic stimulation. PMID- 8474635 TI - Acute cocaine treatment decreases oxytocin levels in the rat hippocampus. AB - We examined the effects of an acute cocaine treatment on oxytocin levels in the whole hippocampus, ventral tegmental area (VTA) and amygdala in ovariectomized rats pretreated with 10 micrograms estradiol benzoate. Cocaine treatment significantly reduced oxytocin levels both in picograms/area and picograms/mg wet weight in the hippocampus but had no significant effect on levels in the VTA and amygdala. These data represent the first evidence for the reduction of oxytocin levels as a result of an acute cocaine treatment. PMID- 8474636 TI - Effect of paraventricular injection of neuropeptide Y on milk and water intake of preweanling rats. AB - This study investigated the effect of paraventricular nucleus (PVN) injection of neuropeptide Y (NPY) on milk and water intake of 2- and 15-day-old sated rats. On the day prior to testing, rat pups were removed from their mothers and implanted with a cannula directed unilaterally at the PVN. On the following day, each pup was implanted with an intra-oral cannula for oral infusion of milk or water that could be swallowed or rejected. Following a 1-hour period fo satiation, each pup received a PVN injection of saline or a single dose of NPY (23.5-235.0 pmol). Milk or water intake was then assessed in a 1-hour test period. Injection of NPY into the PVN enhanced milk and water intake equally at 2 days of age. At 15 days, NPY produced a significantly greater enhancement of milk than water intake. These findings, which are similar to those observed previously with PVN injections of norepinephrine (NE), suggest that: (1) NPY receptors in the PVN, like alpha 2 noradrenergic receptors, are functional very early in the postnatal development of the rat; (2) NPY, in addition to its orexigenic effect, produces a small but significant dipsogenic effect; and (3) NPY may function cooperatively with NE in the PVN to stimulate feeding and drinking beginning at a very early age. PMID- 8474637 TI - Pressure autoregulation is intact after arteriovenous malformation resection. AB - The loss of autoregulatory control of cerebral perfusion to changes in perfusion pressure in tissue remote from an arteriovenous malformation (AVM) has been proposed as the mechanism underlying "normal perfusion pressure breakthrough." This study is the first direct test of this mechanism. Studies were performed during the resection of moderate to large AVMs in 25 patients undergoing 28 procedures under isoflurane anesthesia. Cerebral blood flow (CBF) was measured (xenon-133 method) in the hemisphere adjacent to the nidus before resection after dural exposure (pre), after AVM removal before dural closure at spontaneous systemic blood pressure (post), and, finally, with the mean arterial pressure increased by 20 mm Hg, using phenylephrine (post-BP). AVM resection resulted in a significant enhancement of perfusion in the adjacent hemisphere (30 +/- 2 vs. 25 +/- 1 ml/100g/min, P < 0.01), but no further increase of CBF occurred during increased perfusion pressure (30 +/- 2 ml/100g/min). One patient suffered a postoperative hemorrhage and another developed intraoperative brain swelling during the course of the resection that necessitated staging the procedure. These two patients had the highest increases in CBF, but intact pressure autoregulation. Preserved autoregulation to increased mean arterial pressure after resection does not support a hemodynamic mechanism for the observed increase in CBF from before the resection to after the resection. Pathological events, however, do appear to be related to increases in hemispheric perfusion. PMID- 8474638 TI - Surgical treatment of thalamic arteriovenous malformations. AB - The microsurgical excision of arteriovenous malformations located in the thalamic region in eight patients is reported. Six were located in the posterior aspect of the thalamus and two were located in the anterior. Hemorrhage occurred in all of the cases. Hemiparesis, hemianesthesia, and consciousness disturbance were the most typical clinical features. The supine position with the anterior transcallosal approach was used for anterior dorsal lesions, and the sitting position with the posterior interhemispheric approach was used for posterior dorsal lesions. Total removal was confirmed by angiography in seven patients, and incomplete removal was noted in one patient. There was one death in this group of patients. Memory disturbance was the most common postoperative complication. This complication showed considerable improvement with time. Other complications included homonymous hemianopsia (three patients), hemisensory loss (six patients), and transient hemiparesis (one patient). All survivors (seven patients) were able to return to their occupation after surgery. The vascular input, the location of the malformation, and clinical history are the contributory factors concerning operability. With the modern neurosurgical and anesthesiological facilities, surgical removal of thalamic malformations in selected cases is advisable. PMID- 8474639 TI - Subcortical cerebral hemorrhage with reference to vascular malformations and hypertension as causes of hemorrhage. AB - The authors have reviewed 80 cases of subcortical cerebral hemorrhage, in all of which intraoperative examinations during craniotomy or autopsies were performed. Cases involving trauma and aneurysm were excluded from the study. The diagnosis of subcortical hemorrhage was made by plain computed tomography in all cases. The most common cause of hemorrhage was vascular malformation (68%; 56 cases), in 20 (36%) of which angiographically occult vascular malformations were noted. Hypertension was present in 23 (29%) of 80 cases but was the cause of hemorrhage in only 9 cases (11%). Hypertension was present in 6 (30%) of 20 angiographically occult vascular malformations, all of which were in patients under 65 years. In 12 (75%) of 16 cases of angiographically occult vascular malformations, prolonged high-dose delayed-contrast computed tomography and magnetic resonance imaging were able to provide definite diagnostic information. We recommend that patients with subcortical cerebral hemorrhage, especially those under age 65, with or without hypertension, be carefully examined by prolonged high-dose delayed contrast computed tomography and magnetic resonance imaging for the presence of angiographically occult vascular malformations causing hemorrhage. PMID- 8474640 TI - Clinical studies of de novo aneurysms. AB - Although multiple cerebral aneurysms ae well recognized, a new aneurysm has only rarely been documented after successful treatment for an aneurysm elsewhere. In our consecutive series of 986 patients with intracranial saccular arterial aneurysm collected from 1975 to 1990, nine patients who had previously unverified (hence, de novo) intracranial aneurysms and ruptures at intervals of 4 to 7.5 years after clipping of an initial aneurysm are presented here. All nine had undergone successful treatment of a previous aneurysm; preoperative and postoperative angiography showed not only successful clipping of the first aneurysm but also no incidence of multiple aneurysms. These patients had suffered from hypertension before their second admission. Seven of the nine patients were treated surgically. All patients had experienced angiographical or symptomatic vasospasm after the first subarachnoid hemorrhage. In the second admission however, seven patients who underwent the surgery for a new aneurysm suffered from no vasospasm in spite of the prominent second subarachnoid hemorrhage. Two of the nine patients died of primary brain damage due to the hemorrhage and underwent necropsy. A histological study of a new aneurysm demonstrated the same findings as that of a usual saccular aneurysm. This clinical study of our patients suggests that it is important to control blood pressure for protection against a new aneurysm formation. PMID- 8474641 TI - Cocaine-induced aneurysmal rupture: an emergent negative factor in the natural history of intracranial aneurysms? AB - Recent statistics from the National Institute on Drug Abuse indicate that cocaine abuse continues to be a significant public health problem. Between 1988 and 1990 at Grady Memorial Hospital in metropolitan Atlanta, Georgia, we identified 12 patients in whom subarachnoid hemorrhage was temporally related to cocaine abuse. All 12 patients had underlying cerebral aneurysms that had ruptured. Currently, the incidence of ruptured intracranial aneurysms in patients with cocaine-induced subarachnoid hemorrhage is 84.9% (mean age, 31.1 years; overall mortality, 60.5%). Hypertension is the likely precursive factor in cocaine-induced aneurysmal rupture. Cocaine abuse appears to be a significant negative factor in the natural history of cerebral aneurysms, especially in young adults. We review the epidemiology of cocaine-induced subarachnoid hemorrhage and its effects on the cerebral circulation, and suggest guidelines for patient management. PMID- 8474642 TI - Surgical treatment of moyamoya disease: operative technique for encephalo-duro arterio-myo-synangiosis, its follow-up, clinical results, and angiograms. AB - Moyamoya syndrome is defined as the development of collateral anastomosis pathways at the base of the brain, associated with chronic progressive stenosis of the carotid fork. Both reconstructive vascular surgery and conservative strategies are used to treat this syndrome, but the latter cannot prevent the disease from progressing. We describe the procedure of encephalo-duro-arterio-myo synangiosis (EDAMS), and report the results in 17 patients (28 sides) who underwent EDAMS. The clinical symptoms of moyamoya disease include transient ischemic attacks, reversible ischemic neurological deficits, stroke, seizures, Gerstmann's syndrome, involuntary movements, or mental retardation resulting from the lack of cerebral blood flow. The clinical results of EDAMS were poor in one patient, fair in two, good in five, excellent in eight, and fair on one side and excellent on the other side in one patient. Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in patients undergoing EDAMS. PMID- 8474643 TI - The significance of subarachnoid hemorrhage after penetrating craniocerebral injury: correlations with angiography and outcome in a civilian population. AB - Certain clinical factors are considered to have an effect on patient outcome after penetrating missile injury. These include bilateral hemispheric injury, ventricular hemorrhage, intracerebral hemorrhage, mass effect, and missile or bony fragmentation. The relationship of subarachnoid hemorrhage (SAH) after penetrating craniocerebral injury and outcome is unknown. In addition, controversy exists regarding the role of angiography and the incidence of traumatic intracranial aneurysm in this population. Finally, can we assume that the incidence of traumatic intracranial aneurysm is equal in military and civilian populations, given the absence of penetrating shrapnel injury in civilian populations? Now that computed tomography has supplanted angiography as the primary diagnostic modality, increasing vigilance on the part of the physician and examination of angiography in high-risk patients should allow for enhanced outcome. We evaluated 100 patients with a diagnosis of cerebral gunshot wound over a 12-month period. All patients were evaluated neurologically at the time of admission and had imaging studies. Thirty-one patients with radiological evidence of SAH on computed tomography underwent angiography. Angiograms were limited to the side of the injury in patients with single-lobe or unilateral multilobe injuries and were bilateral in patients with bilateral hemispheric involvement. One intracranial aneurysm (3.2%) was documented and treated surgically. In those patients who died within 48 hours of admission, 68% had SAH as compared with only 17% of those surviving. Outcome was based upon neurological evaluation at the time of discharge and at the time of clinical follow-up at 3 and 6 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474644 TI - Sigmoid sinus thrombosis after closed head injury in children. AB - In the literature, clinical descriptions of sigmoid sinus thrombosis occurring after closed head injury in children are rare. One to 5 days after trauma to the back of the head, five children (aged 1 to 7 yr) presented with gait ataxia, vomiting, and headache. Trauma was mild in four children. Computed tomography of all the children, performed within 5 days after the injury, showed focal hyperdensity in the region of the left sigmoid sinus. Four children had extra axial hyperdense collections along the left transverse sinus, and three had skull fractures adjacent to the left sigmoid sinus. Magnetic resonance imaging (MRI) of all the children, performed 2 to 6 days after injury, showed left sigmoid-sinus thrombosis and decreased flow or thrombosis within the lateral third of the left transverse sinus. All the children had MRI scans 4 to 6 weeks after their diagnosis and were followed up for 1 to 12 months. In four children whose symptoms subsided completely within 2 to 10 weeks, MRI showed recanalization of the sigmoid sinus within 4 to 6 weeks after injury. In one child whose symptoms resolved after 6 months, sigmoid-sinus thrombosis persisted with the formation of collateral flow. We conclude that traumatic sigmoid-sinus thrombosis should be suspected when a child has persistent or delayed gait ataxia and vomiting after injury to the back of the head. Computed tomography characteristically demonstrated focal hyperdensity within the sigmoid sinus that we term the dense sigmoid-sinus sign. Because the sinus recanalized and the symptoms subsided in most children within 6 weeks, we conclude that prophylactic medical or surgical intervention is not indicated. PMID- 8474645 TI - Multimodality monitoring as a guide to treatment of intracranial hypertension after severe brain injury. AB - Transcranial doppler measurements of blood flow velocity in the middle cerebral artery were made during treatment of raised intracranial pressure (ICP) in 22 patients with severe brain injury. Twenty patients also had continuous measurement of arterial and jugular bulb venous oxygen saturation (SJO2). The transcranial Doppler parameters studied included both mean flow velocity and pulsatility index (PI). Successful treatment was defined as a reduction of ICP to less than 20 mm Hg with improvement or preservation of cerebral perfusion pressure (CPP) above 60 mm Hg. Successful therapy was associated with a significant rise in SJO2 and reduction of cerebral arteriovenous oxygen content difference (AVDO2) and PI only when the pretreatment CPP was less than 60 mm Hg. An increase in CPP beyond 70 mm Hg did not further improve cerebral oxygen delivery and PI, suggesting that autoregulation became a factor above this CPP threshold. Treatment failure during administration of hypnotic drugs resulted in a reduction in arterial pressure, CPP, SJO2, and mean velocity and in an increase in PI and AVDO2, despite a decrease in ICP. CPP is the most important parameter to monitor during ICP therapy. It should be maintained above 70 mm Hg in patients with severe brain injury. PMID- 8474646 TI - Supratentorial low-grade astrocytomas in adults. AB - One hundred seventy-nine adult patients with supratentorial low-grade astrocytomas were treated during a 10-year period. Retrospectively, a series of nine factors were evaluated with simple and multivariate analysis to determine their importance in predicting length of survival. Four appear highly significant (P < 0.005): age, preoperative Karnofsky Performance Scale score, histological grade, and type of surgical removal. Eighty percent of patients with total removal were alive at 5 years compared with 50% with incomplete surgery and 45% with biopsy. For the group under study, the mean time for recurrence was 52 months. For patients surviving for more than 1 year, the chance of being recurrence free went from 75% at 3 years to 25% at 10 years. Among the entire population, the influence of radiotherapy was not obvious: 65% of patients were alive at 5 years without radiotherapy compared with 55% with radiotherapy. A significant difference appeared only for patients older than 40, with incomplete removal (P < 0.05); this difference did not apply to younger patients. The need for postoperative radiotherapy in all patients with subtotal removal, irrespective of their age, has not been demonstrated by this study. PMID- 8474647 TI - Delayed computed tomography contrast enhancement patterns in biopsy proven cases. AB - After a stereotactic brain biopsy of intracranial lesions, many neurosurgeons routinely obtain a noncontrast computed tomographic scan to rule out hemorrhage. We have observed there is often a significant delayed contrast enhancement on this postoperative scan, and the pattern of this enhancement frequently differs from the preoperative pattern. To assess these changes and to determine if they are related to lesion pathology or other clinical factors, the pre- and postoperative scans of 89 patients who underwent stereotactic biopsies were reviewed. Despite an average time delay of 153 minutes between scans, 81% of the lesions enhanced similarly or better on the postbiopsy image. One lesion enhanced only on the postoperative image, and in two cases, new lesions were seen postoperatively. Ring and other enhancing lesions tended to fill in with time, becoming homogeneous. The area of contrast enhancement increased in 83%. The borders of the lesions tended to become less sharp with time. No patterns of delayed enhancement, which give histologically definitive diagnostic information, were found. The tendency toward an increased area of contrast enhancement with time suggests that computed tomographic scans taken at the time of contrast injection may not show the true extent of the lesion. For patients undergoing computed tomography-guided stereotactic biopsies or radiosurgery of poorly enhancing lesions, the localization scan might be delayed after the administration of contrast medium to improve resolution and target selection. PMID- 8474648 TI - Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy. AB - We examined the relationship of preoperative unilateral memory function and quantitative hippocampal histology in patients undergoing anterior temporal lobectomy for the treatment of complex partial seizures. Recognition memory (objects, words, figures) was assessed preoperatively for each hemisphere by the intracarotid amobarbital procedure in 23 patients (mean age at the time of operation, 30.2 yr; standard deviation, 9.2; mean age at the time of seizure onset, 12.3 yr; standard deviation, 8.6) without tumor. Memory scores were the total number of items recognized, adjusted for guessing. Histological examination of the anterior 20 to 30 mm of hippocampal tissue was accomplished in all patients. The degree of unilateral memory impairment ipsilateral to the seizure focus was significantly correlated with decreased neuronal density in the hilar (r = 0.66, P < 0.001) and dentate granule (r = 0.61, P < 0.002) regions, but not in the CA1 (r = 0.10, P = not significant) or CA2-3 (r = 0.35, P = not significant) regions. Memory performance with the contralateral hemisphere was not significantly correlated with ipsilateral hippocampal densities. These data support the role of the hippocampus in human memory and show further evidence of hippocampal subfield specificity in the relationship between memory performance and neuronal cell loss. Further studies of the dentate granule and hilar regions in relation to human memory are warranted. PMID- 8474649 TI - Stereotactic percutaneous lumbar discectomy. AB - Sixty-nine patients with documented and contained disc herniations underwent percutaneous discectomy. The procedure was carried out with a new stereotactic device mounted on the floor and positioned over the computed tomographic scanner. In each instance, this device provided accurate insertion of the needle and localization of the aspiration probe (Nucleotome) within the appropriate area of the disc. Aspiration of the herniated nucleus pulposus was accomplished in every patient, and no complications were encountered. PMID- 8474650 TI - Biomechanical effects of laminectomy on thoracic spine stability. AB - Thoracic columns (T1-L1 levels) from 15 fresh human cadavers were used to quantify alterations in the biomechanical response after laminectomy. Eight specimens were tested intact (Group I); the remaining seven preparations were tested after two-level laminectomy (Group II) at the midheight of the column. All specimens were fixed at the proximal and distal ends and loaded until failure. Force and deformation were collected by use of a data acquisition system. Failure of the Group I specimens included compressive fractures with or without posterior element distractions, generally at the midheight of the column. Group II preparations failed at the superior aspect of laminectomy or at a level above laminectomy, suggesting an increased load sharing. Biomechanical responses of the Group II preparations were significantly different (P < 0.05) from those of the Group I specimens at deformations from the physiological to the failure range. In addition, failure forces for Group II preparations were significantly lower (P < 0.001) than for Group I specimens. The stiffness and energy-absorbing capacities of the laminectomized specimens were also significantly different (P < 0.05) from those of the intact columns. In contrast, the deflections at failure for the two groups were not statistically different, suggesting that the human thoracic spine is deformation sensitive. Our data demonstrate that a two-level laminectomy decreases the strength and stability of the thoracic spine throughout the loading range. Although this is not a practical concern with an otherwise intact vertebral column, laminectomy, when other abnormalities such as vertebral fracture, tumor, or infection exist, may require stabilization by fusion and instrumentation. PMID- 8474651 TI - Significance of the rate of systemic change in blood pressure on the short-term autoregulatory response in normotensive and spontaneously hypertensive rats. AB - Cerebral autoregulation, the physiological regulatory mechanism that maintains a constant cerebral blood flow (CBF) over wide ranges of arterial blood pressure, was investigated in normotensive and spontaneously hypertensive rats by means of laser-Doppler flowmetry. Systemic arterial hypertension was produced at rates ranging from 0.02 mm Hg/second to 11 mm Hg/second by constant infusion of epinephrine and norepinephrine. Systemic arterial hypotension was produced at rates ranging from -0.03 mm Hg/second to -12 mm Hg/second, either by bleeding the animals into a reservoir or by compressing the abdomen. In those cases with a low rate of change in systemic arterial blood pressure (SABP), the measurements lasted for 5 +/- 2 minutes, and in those with a high rate of change in SABP, measurements lasted for 40 +/- 30 seconds. The purpose was to record the time of onset and course of autoregulation in the basal ganglia in response to slow or rapid changes in SABP. CBF in the basal gray matter remained at baseline values (i.e., autoregulation was functioning) if the rate of increase of SABP did not exceed a critical value (0.10 mm Hg/second in the normotensive rats; 0.35 mm Hg/second in the spontaneously hypertensive rats). When hypertension was produced at faster rates, CBF followed arterial blood pressure passively, and no autoregulatory response was observed for 2 +/- 1 minutes. Hypotension did not change the baseline CBF when it was not produced at a rate faster than -0.4 mm Hg/second in normotensive rats and -0.15 mm Hg/second in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474652 TI - Nonmuscle arterial constriction after subarachnoid hemorrhage: role of growth factors derived from platelets. AB - Recent studies have shown that myofibroblasts cultured from spastic arteries after subarachnoid hemorrhage (SAH) can produce contractile forces and that cerebrospinal fluid obtained from SAH patients accelerates this contraction. Myofibroblast-populated collagen lattices were used to evaluate the roles of polypeptide growth factors considered to be released from intraluminal accumulated platelets. The myofibroblasts, obtained at autopsy from human cerebral arteries of victims of vasospasm, caused contractile forces by compacting collagen fibrils in the matrix. Transforming growth factor beta 1 (TGF beta 1) and platelet-derived growth factors aa and bb (PDGFaa and PDGFbb) accelerated this contraction in a dose-dependent manner. In the presence of TGF beta 1 at 1 or 10 ng/ml, PDGFaa at 10 ng/ml, or PDGFbb at 10 ng/ml, lattice areas were reduced to 69.5 +/- 1.9% (mean +/- standard deviation) (P < 0.001), 63.3 +/- 0.4% (P < 0.001), 66.5 +/- 3.0% (P < 0.01), or 74.4 +/- 1.7% (P < 0.01) of the control on Day 6, respectively. The combination of subthreshold doses of TGF-beta 1 and PDGFaa created a stimulatory effect that appeared to act synergistically. Furthermore, myofibroblast-populated collagen lattices made with cells preincubated with TGF-beta 1 showed more rapid compaction with or without the presence of stimulants such as post-SAH cerebrospinal fluid. These results suggest that, in addition to other possible factors in the post-SAH cerebrospinal fluid, growth factors derived from accumulated platelets may play an important role in arterial constriction caused by nonmuscle components after SAH, by single or multiple mechanisms. PMID- 8474653 TI - Risks of anticoagulation therapy after experimental corticectomy in the rat. AB - To determine the optimal postoperative interval after which heparin therapy can be safely initiated, a rat model for experimental craniotomy and corticectomy was developed. In 50 rats (100 lesions), heparin therapy was initiated 1, 2, 3, 5, or 7 days after standardized bilateral frontal corticectomy and was continued for 7 days. Intraperitoneally administered heparin, 75 to 100 U/kg.h, was continuously given to maintain the activated partial thromboplastin time in one of two ranges: therapeutic (1.5-3 times control) or supratherapeutic (> 3 times control). The size of intracranial hemorrhage was determined from coronal brain sections by automated image analysis. No significant hemorrhage was observed in control (saline infusion) animals or in rats receiving therapeutic doses of heparin beginning more than 24 hours after surgery. Small (10-50 mm3) and large (> 50 mm3) hemorrhages were frequent at all intervals up to 5 days in animals with supratherapeutic activated partial thromboplastin time (P < 0.01). Judicious heparin therapy may be safely initiated at 48 hours after craniotomy and corticectomy in rats, whereas supratherapeutic anticoagulation is associated with intracranial hemorrhage at intervals of up to 5 days. PMID- 8474654 TI - Prevention of postoperative intracerebral hemorrhage with topical recombinant factor XIII in the rat. AB - Factor XIII is an endogenous clotting factor that retards thrombus degradation by cross-linking fibrin. To determine the efficacy of Factor XIII as a topical clot stabilizing agent in preventing postoperative hemorrhage associated with coagulopathy, a rat model of experimental craniotomy and standardized bilateral frontal corticectomy was developed. In 25 rats (50 lesions), recombinant human Factor XIII or placebo solution was topically applied to corticectomy cavities after hemostasis was achieved; each animal served as its own control. In 20 rats, heparin sulfate (100 U/kg.h) was initiated intraperitoneally 3 days after surgery and was continually administered by an Alzet pump for 7 days, compared with a control group of 5 rats receiving saline intraperitoneally. The volume of intracranial hemorrhage was quantitatively determined from coronal sections by use of automated image analysis. Large (> 50 mm3) intracerebral hemorrhages were significantly more frequent in placebo (60%)- compared with recombinant Factor XIII (15%)-treated lesions (P < 0.01) in animals receiving heparin. The topical application of clot-stabilizing agents such as Factor XIII may reduce the risk of postoperative intracranial hemorrhage, especially in high-risk patients with coagulopathy. PMID- 8474655 TI - Meningiomas. AB - This article reviews the recent literature on the pathogenesis and pathology of meningiomas, contemporary techniques of surgical resection, and new nonsurgical treatments, including radiation and hormone therapy. Factors predisposing to meningioma formation include female sex, previous ionizing radiation, and Type 2 neurofibromatosis. The first factor may act through the expression of sex hormone receptors, especially the progesterone receptor, in these tumors; the other two probably act by causing a deletion on Chromosome 22. The pathological classifications of meningiomas include the traditional division into histological subtypes and the World Health Organization classification that selects characteristics that may lead to recurrence. There is an increasing emphasis on proliferative indices and other characteristics that may predict aggressive behavior in these tumors. On computed tomography, meningiomas are enhancing, well marginated, dural-based lesions that may have considerable surrounding edema; the cause of the edema is uncertain but may result from secretory products of the tumor. Magnetic resonance imaging with enhancement will demonstrate these lesions accurately and can be used for three-dimensional reconstruction as well. Computed tomography and magnetic resonance imaging have largely replaced angiography in the preoperative diagnosis of meningiomas, but angiographic embolization may be a useful operative adjunct. Although meningioma surgery is sometimes thought of as benign and curative, the reported surgical mortality rate is as high as 14.3% and the reported 10-year survival rate after surgery varies from 43 to 77%. Surgery has advanced most in the management of suprasellar, cavernous sinus, clivus, tentorial, and posterior fossa meningiomas, because new approaches and a better understanding of anatomy have allowed more radical resection. There is still substantial morbidity associated with surgery in these regions, however, and the long-term recurrence rates are still unknown for these new radical techniques. For convexity, parasagittal, lateral sphenoid wing, and olfactory groove meningiomas, complete resection should be the goal and operative morbidity appears to be low. There is a high recurrence rate after surgery. With apparent total removal, the recurrence rate varies from 9 to 20% at 10 years, with subtotal resection varying from 18.4 to 50%. The degree of resection appears to be most important in recurrence, but histopathological features are also important. Recently, radiation therapy has been recognized as a useful adjunct to surgery, and with radiosurgical techniques may become more important in the future. Antiprogesterone therapy appears to have had some success as well, and it or other hormonal therapy may be another future option for residual or recurrent meningiomas. PMID- 8474656 TI - Symptomatic intradural adrenal adenoma of the spinal nerve root: report of two cases. AB - The second and third cases of an adrenal adenoma involving the intraspinal space, a rare location for a lesion that occurs rather commonly at a variety of extraneural sites, are reported. The first patient, a 16-year-old girl with a 3 month history of radicular pain, was found to have an intradural, extramedullary mass arising on a spinal nerve root. Its resection resulted in cure. The second patient, a 63-year-old woman with a 10-month history of low back pain with radiation to both lower extremities, had a similar mass arising from one of the nerve roots of the cauda equina. In both cases, ultrastructural examination of these demarcated, oncocytic, lipid-rich lesions demonstrated abundant smooth endoplasmic reticulum and mitochondria with tubular cristae. The presence of steroidogenic enzymes was noted on immunohistochemical examination. The literature is reviewed, as is the differential diagnosis of these rare lesions. PMID- 8474657 TI - Parasellar epidural hydatid cysts. AB - We report two rare cases of parasellar epidural hydatid cysts. Among the 64 patients with intracranial hydatid cysts we have treated in the past 20 years, only these two cases were located epidurally. Because the location and the computed tomographic characteristics were so different from the other cysts, the preoperative diagnosis was difficult to make. We were unable to remove the cysts without rupturing them because they were tightly surrounded. Both patients underwent surgery twice because of a recurrence. The treatment of this kind of case requires further discussion. PMID- 8474658 TI - Hearing impairment resulting from a pineal region meningioma. AB - Because of extensive interconnections within the auditory pathways, hearing impairment from a central origin is rare. We describe a patient with a large pineal region meningioma in whom hearing loss was the predominant symptom. The patient promptly recovered hearing after the surgical removal of the tumor. The mechanism of this phenomenon is discussed. PMID- 8474659 TI - Quadraparesis after a shunting procedure in a case of cervical spinal neurinoma associated with hydrocephalus: case report. AB - The authors report a rare case of cervical spinal neurinoma in a patient who presented with symptoms originating from hydrocephalus. Her symptoms improved after a ventriculoperitoneal shunt was inserted, although progressive quadraparesis appeared when she began to walk. Magnetic resonance imaging revealed a cervical tumor. When it was removed, the patient's quadraparesis improved. Associated spinal tumors should be considered in the treatment of hydrocephalus of unknown origin. PMID- 8474660 TI - Thiamine-deficient encephalopathy in association with aneurysmal subarachnoid hemorrhage: a case report. AB - An alcoholic man who was admitted with an acute onset of neck pain and confusion was diagnosed as suffering from a subarachnoid hemorrhage after rupture of an anterior communicating artery aneurysm. Additionally, he showed a bilateral 6th nerve palsy of variable extent. The postoperative course was complicated by pulmonary edema and adult respiratory distress syndrome. He died on Day 28 after admission. At autopsy, surprisingly, the concomitant diagnosis of acute thiamine deficient encephalopathy was made. Thiamine had been given only in minimal amounts during hospitalization. We describe the striking clinicopathological features of this previously undocumented case and consider the relationship between the two central nervous diseases. PMID- 8474661 TI - Fastigial pressor response observed during an operation on a patient with cerebellar bleeding--an anatomical review and clinical significance. AB - The fastigial pressor response (FPR) consists of an abrupt rise in blood pressure and tachycardia with hyperpneic response. The FPR is an important sign in posterior fossa surgery for respiration in postoperative patients. The authors experienced a distinct pressor, tachycardiac, and hyperpneic response elicited when controlling bleeding using a bipolar coagulator forceps at the subfastigial white matter in a 72-year-old man with cerebellar hemorrhage. This response was confirmed by bipolar electrodes, which produced a weak current under deeper anesthesia by increasing the concentration of enflurane. The postoperative course of this patient was uneventful. A FPR was suggested to be mediated by axons passing between the nucleus fastigii and the fourth ventricle. These commissural fibers mediating the FPR were suggested to be countercurrent efferent pathways from both sides of the nucleus parabrachialis lateralis, located at the dorsolateral corner of the rostral pons. The authors conclude that the partial destruction of the subfastigial commissural fiber bundle did not result in permanent respiratory deficit. Fatal respiratory disturbance might be anatomically suggested by completely cutting off this fiber bundle. PMID- 8474662 TI - Correlation of contralateral stenosis and intraoperative electroencephalogram change with risk of stroke during carotid endarterectomy. PMID- 8474663 TI - Intramedullary cavernous angiomas of the spinal cord: clinical presentation, pathological features, and surgical management. PMID- 8474664 TI - Intracavernous cavernous hemangioma: an unpublished but reported case. PMID- 8474665 TI - The education of a neurosurgeon: the two cultures revisited. PMID- 8474666 TI - [Clinical use of cerebral elastance and intracranial dynamics measurements]. AB - The treatment of Intracranial Pressure (ICP) requires not only the determination of the pressure but also some kind of estimate of the relationship between intracranial volume and actual pressure. The measurement of the Pressure Volume Index (PVI) offers a quantitative assessment of such a relationship, provided that the measurement is safe and accurate. In 98 comatose patients admitted to the Intensive Care Unit for the treatment of head injury or subarachnoid hemorrhage the ICP was continuously recorded using ventricular or subdural catheters. In 68 patients the PVI was measured using the bolus technique every 12 hours; the intracranial dynamics was assessed according to Marmarou's equations. The preliminary part of the work reviewed the methodology: the interobserver variability was studied and the differences between the PVI data obtained through addition or withdrawal of fluid were determined. The data obtained by different observers did not differ substantially, due to the clear establishment of rules for the measurement. The PVI data obtained withdrawing fluid were lower than the data produced adding volume but the mean PVI calculated after 6 bolus changes of the intraventricular volume reached a good correlation coefficient (> 0.8) with all the measurements. After that the clinical use of the PVI was tested. The patients with a PVI lower than 15 ml showed an increased risk of developing intracranial hypertension in the first 72 hours after trauma of SAH. The group of patients with an intracranial compliance lower than 0.5 had a mortality rate of 27.3%, compared with the rate of 14.3% showed by the patients with a greater Compliance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474667 TI - [Transcranial Doppler in the diagnosis of brain death]. AB - The delay in the diagnosis of brain death represents a cause of deficiency of organs for transplant. In this prospective study we evaluate the role of Doppler sonography, to investigate typical velocimetric profiles of brain death, and to evaluate the delay between finding the typical profiles and diagnosis expressed according to law. In this ongoing study, we evaluated 32 patients affected from serious primitive intracranial diseases (Glasgow Coma Scale < or = 7). Of the 32 patients examined, 18 underwent or still remained in brain death. All the patients showed typical profiles, classified in 3 fundamental types. Start of monitoring, according to the current law, showed a delay from 12 to 27 hours. The authors conclude that Transcranial Doppler and Doppler c.w. represent an early and sensitive technique, rightly to include in the procedure of the diagnosis of brain death. PMID- 8474668 TI - [Multiple organ system failure: analysis of oximetry parameters among survivors and non-survivors]. AB - The authors have studied the relationship between SvO2 and many parameters of oxygenation in MOSF patients specially in surviving patients and not surviving ones. They found that there is a close correlation between SvO2 and CI in the survivors indicates that, in these patients, we can increase cardiac activity to improve the cellular demand. PMID- 8474669 TI - [Rationalization of transfusional therapy in elective surgery. Our experience]. AB - The paper reports the authors' experience regarding the rationalisation of transfusional therapy. The high risks of infection or damage to the immune system have highlighted the need to review the approach used by the anesthetist, surgeon or hematologist resulting in major cultural changes and the development of methods for the use of autologous blood. The study was carried out by comparing 2 similar periods of surgical activity in which the sole variant was the different attitude of the anesthetist who utilised blood transfusion on the basis of pre, intra and postoperative hematocrit values; in addition, the Authors report the results obtained in a group of patients enrolled for EIN. They observed that by using simple rationalisation a 30% saving, equivalent to 101 blood units, was achieved; EIN was performed in 20 patients out of the 32 enrolled with an effective 20% saving equivalent to 40 units; calculating the theoretical saving which could be obtained by total EIN and rationalisation, a saving of as much as 58% equivalent to 198 units could be achieved. Even if many aspects still require definition, good rationalisation, even using simple techniques, coupled with the availability of autologous blood certainly makes blood transfusion safer and less expensive. PMID- 8474670 TI - [Validity of computer simulation in closed circuit anesthesia]. AB - Developing a computer program to simulate the uptake, distribution, and elimination of inhalational anesthetics allow the anesthesiologist to address specific problems, but intense skills are required to translate the involved process first into a set of mathematical equations and then into a satisfactory computer program. The first step is facilitated by solutions offered in the literature. The second step by personal computer program now currently available as Gus, this program simulates anesthetic uptake and distribution using a numerical model with 12 compartments. Transport of anesthetic agents among the compartment occurs via convection of gas and blood during discrete iteration of the simulation. As initial clinical validation of the linear 12 compartment basic model the current study examined the predictive performance in 20 patients by comparing quantitatively the predicted and the measured alveolar concentration time profiles after achievement of end tidal concentration of isoflurane (C-alv%) injected into a heated chamber (75 degrees) and then transported in closed circuit system during mechanical ventilation. With regard to the use of isoflurane 20 patients were adequately anesthetized with only 88 ml of liquid isoflurane and that is the same in simulation achieved by computer. PMID- 8474671 TI - [The major nerve trunks are not the primary action site of intravenous regional anesthesia]. AB - In a patient suffering from a deep penetrating wound of the left forearm and radial nerve injury, the administration of intravenous regional anesthesia (IVRA) was followed by prompt analgesia of the whole arm while intense pain could still be elicited by stimulating radial nerve stump. Complete radial nerve block was present 10 min later confirming that initial blockade of nerve terminals substantially contributes to IVRA and suggesting that a 10 min delay is indicated for optimal analgesia after IVRA whenever a major nerve injury is suspected. PMID- 8474672 TI - [Buprenorphine as preanesthetic medication in peridural anesthesia]. AB - Buprenorphine was used as a preanesthetic drug for peridural anaesthesia. The aim of the study was therefore to evaluate the sedative/anxiolitic activity of this drug as compared to prometazine and diazepam. Two hundred male patients, divided into two groups (A and B), who were to undergo urological surgery under peripheral anesthesia, were included in the study: L2/L3 or L3/L4 epidural block. The group A patients were premedicated with buprenorphine; the group B patients received traditional anesthetic. The following factors were evaluated: the course of the AP and CF, the state of intraoperative sedation, the presence of side effects and data obtained, elaborated with a statistical test constructed to compare the percentages in two independent samples. There were no statistically significant variations of the AP and CF in the two groups. Additional sedatives were administered to 56.2% of the patients in group B and to only 27.1% in group A, premedicated with buprenorphine. Thirty seven percent of the group A patients and 10% of the group B patients presented preoperative nausea. The authors believe that the buprenorphine/atrophine association should be encouraged for pre anesthesia when operations in peridural anesthesia are to be conducted, as it provides a state of constant sedation, avoiding rather ineffective pharmacological mixtures. PMID- 8474673 TI - [Short version of the pain questionnaire: influence of age on the choice of terms]. AB - We proposed the QUID to 1148 persons divided into 5 groups and we looked for diversity in the choice of terms in relation to age and sex. The purpose was to elaborate one or more short versions of QUID to meet in a specified way, the requirements of simplicity, flexibility and specificity that came out from pain practice. PMID- 8474674 TI - [Group of study SIAARTI of anesthesia and recovery for neurosurgery and neurology. Present and future]. AB - The authors present the results of a survey of anesthesiologists members of the "SIAARTI (Societa Italiana di Anestesia, Analgesia, Rianimazione e Terapia Intensiva) Committee for anesthesia and critical care in neurosurgery and neurology". Among the aims of the survey, was to evaluate when the interest in neuroscience of the members of this group started, and the clinical work dedicated to neuroanesthesia and critical care. At present, the group has grown to 143 members. In the questionnaire 105 members indicated the topic discussed for the medical degree thesis, and 87 indicated the thesis discussed for the board in anesthesia. As emerged from the topic of the thesis discussed for the medical degree, in 47% of the responders the interest in anesthesia began during the college. Of this, 6% chose a topic in neuroanesthesia and critical care. During the residency, the interest in neuroscience increased to 33%, that is 32 out of 97 responders discussed a thesis in neuroanesthesia and critical care. Forty-eight per cent of the members performs clinical work "exclusively" in neuroanesthesia, while 39% does it "mainly", and only 13% works in neurosurgery "fiftfully". PMID- 8474675 TI - [Spinal activity and brain death]. PMID- 8474676 TI - [Intensive medicine in a metropolitan area. An epidemiologic study. Multicenter Italian Group of Research in Intensive Therapy (GIRTI)]. AB - This report is an epidemiological study concerning the description of intensive care medicine in North Italy. 2710 patients were enrolled in 1988 in 14 ICU. Mean admission SAPS was 12.0 +/- 0.1 point, TISS 29.9 +/- 0.2 points; ICU stay 9.1 +/- 0.2 days; ICU mortality 23% and hospital mortality 30.4%. The higher stay and mortality were recorded in patients suffering from chronic illness; mortality was significantly related to the severity of the clinical condition and the main diagnosis at the ICU admission. PMID- 8474677 TI - [Acute voluntary poisoning with propafenone. A clinical case]. AB - Propaphenone hydrochloride in an antiarrhythmic which belongs to class 1C. In recent years it has been widely used in clinical medicine, mainly in the treatment of hyperkinetic arrhythmia. Given the enormous quantity of the medication taken, the description of the case seemed opportune as well as that of the clinical manifestations and electrocardiographic modifications linked to the parmakinetic and electrophysiological characteristics. PMID- 8474678 TI - [Peridural anesthesia for cesarean section in a patient with inoperable cerebral angioma]. AB - Anaesthesia for caesarean section in patients with cerebral artero-venous malformations (CAVM) is a controversial matter. We describe a case of a primiparus woman with an inoperable CAVM delivered by CS under epidural anaesthesia. Epidural anaesthesia can be a valid alternative to general anaesthesia as it provides excellent analgesia allowing an accurate assessment of the neurological conditions of the mother and avoiding opioids and/or hypotensive drugs, potentially dangerous to the foetus, to blunt the hypertensive response to intubation. The accidental dural puncture is to be avoided with extra-careful technique. The epidural injection must be made either very slowly or with an incremental technique to avoid any increase in intracranial pressure. Hypotension must be corrected promptly to maintain cerebral perfusion pressure. PMID- 8474679 TI - Neurogenesis persists in the subependymal layer of the adult mouse brain. AB - Neurogenesis of olfactory bulb granule cells is known to persist in adult rats where, in some strains, the bulbs grow throughout life. In mice, bulb growth ceases early in adulthood and here we ask if granule cell neurogenesis persists after the bulbs have stopped growing. By injecting adult mice with bromodeoxyuridine (BrdU) and allowing short and long survival times, we found that new cells form in the subependymal layer and that they migrate subsequently into the olfactory bulbs where they acquire the nuclear morphology of granule cells and express neuron-specific markers. Using [3H]thymidine, we found that most of these adult-generated granule neurons persist within the bulbs for at least 16 weeks. This shows the persistence of neurogenesis and neuronal migration in adult animals in which the olfactory bulbs have stopped growing. PMID- 8474680 TI - Selective release of serotonin by endogenous alkaloids, 1-methyl-6,7-dihydroxy 1,2,3,4-tetrahydroisoquinolines, (R)- and (S)salsolinol, in the rat striatum; in vivo microdialysis study. AB - Dopamine-derived 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines, (R)- and (S)salsolinol, released an enormous amount of serotonin in the rat striatum; the concentration of serotonin increased from undetectable level to 2.53 +/- 0.12 and 3.69 +/- 0.01 microM after perfusion of (R)- and (S)salsolinol, respectively. Salsolinols increased extracellular dopamine level, but to a much lesser degree than serotonin. Other naturally occurring isoquinolines with catechol structure released serotonin and dopamine, but salsolinols were the most potent and selective releaser of serotonin. Serotonin release by salsolinols may be involved in some psychiatric symptoms in L-DOPA therapy or alcoholism. PMID- 8474681 TI - Investigating the role of anaesthetics on the rostral ventromedial medulla: implications for a GABAergic link between ON and OFF cells. AB - Two classes of cells in the rostral ventromedial medulla (RVM), ON and OFF, are important in the descending modulation of noxious input. It is thought that these two cell classes communicate, at a local level, with each other to control the RVM's descending modulation. Systemic morphine was given to rats anaesthetized with either pentobarbital (a GABA agonist) or with ketamine (a non-competitive NMDA receptor antagonist) and xylazine. The spiking activity of the ON and OFF cells was recorded. The typical ON cell inhibition by morphine was observed in rats under both anaesthetics. However, the OFF cell excitatory response to morphine was seen in the ketamine but not in the pentobarbital-anaesthetized animals. The implications for a GABAergic connection between these two classes of cells are discussed. PMID- 8474682 TI - Ischemic neocortical protection with U74006F--a dose-response curve. AB - A dose-response curve for the lipid peroxidation inhibitor U74006F was established in a rat forebrain ischemia model. Transient forebrain ischemia was induced by bilateral carotid occlusion plus controlled hypotension (50 mmHg) for 10 min. U74006F was administered at doses of 0.3, 1, 3, 7, or 10 mg/kg 30 min prior to ischemia. Control animals received vehicle (0.02 M citrate buffer in 0.8% NaCl). Brains were perfusion-fixed on day 7 post-ischemia for histopathological examination. For both the hippocampus and striatum, neuronal injury was not significantly different between groups. Within the neocortex ischemic neuronal injury was significantly less (P < 0.05) in the 7 mg/kg U74006F treated group compared to the control, 1 mg/kg, or 3 mg/kg U74006F-treated groups. PMID- 8474683 TI - Quinolinic acid lesion of the striatum induces impairment in spatial learning and motor performance in rats. AB - Injection of quinolinic acid (QA) into the striatum of rats is known to produce neuropathological and neurochemical alterations similar to those observed in Huntington's disease (HD). One clinical feature of HD patients is cognitive impairment. Two weeks after stereotaxic injection of either QA (240 nmol) or solvent in rats spatial learning was tested in the Morris water maze. QA lesioned animals required more time to find the hidden platform. The swim speed was reduced in all trials compared to the controls. The swim distance itself was longer and the amount of swim distance along the side wall was significantly higher in QA lesioned rats. The present results suggest that QA lesion of the striatum leads to deficit in motor performance and in spatial learning. PMID- 8474684 TI - Postnatal development of vasoactive intestinal polypeptide-containing neurons in the visual cortex of normal and dark-reared rats. AB - The effects of dark rearing on the distribution and density of vasoactive intestinal polypeptide (VIP)-containing neurons in the visual cortical areas (17, 18 and 18a) of rats during postnatal development were examined immunohistochemically. Two groups of Wistar rats, one reared under normal lighting conditions and the other in complete darkness from birth, were used. VIP neurons showed a fairly similar distribution in the three visual areas, being predominantly present in layers II and III. Their pattern of development was found to be similar in the normal and dark-reared animals and was characterized by a marked increase from postnatal day (P) 7 to P21, followed by a gradual diminution to 24-31% of peak densities. Counts of labeled neurons at all ages examined showed that their density was similar in both groups at P7 and P14, but progressively greater in dark-reared animals from P21 and thereafter, so that they only fell to 38-43% of peak densities. Thus, by 60 days of age densities of VIP-labeled neurons in areas 17, 18 and 18a in dark-reared rats were 57%, 49% and 51% higher than in the corresponding areas of the age-matched control rats. These results indicate that the normal decline in the numbers of VIP neurons is not so marked under the conditions of dark rearing. PMID- 8474685 TI - Properties of single Na(+)-activated K+ channels in cultured central neurons of the chick embryo. AB - Na(+)-activated K+ channels (IK[Na]) of cultured chick brainstem neurons do not run down following excision of inside-out patches, but this occurs within seconds to minutes in cultured chick olfactory bulb neurons. IK[Na] channels of chick brainstem neurons exhibit a main conductance state of 95-105 pS, and also express multiple sub-conductance states. These channels have complex kinetics, with multiple closed and main conductance states. The average lifetime of the main conductance state is not dependent on the Na+ concentration used to activate the channels. PMID- 8474686 TI - Beta A4 protein deposition in familial Alzheimer's disease with the mutation in codon 717 of the beta A4 amyloid precursor protein gene and sporadic Alzheimer's disease. AB - Beta A4 protein immunoreactivity in the neocortex and hippocampus of familial Alzheimer's disease (AD) including the case with the beta A4 amyloid precursor protein (APP) gene mutation in codon 717 (APP717 Val-->Ile) and sporadic cases of AD is described. A semi-automatic image analysis system was used to quantify beta A4 protein load in the isocortex of the frontal and temporal lobes and in subfields of the hippocampus. Immunoreactivity was measured in ten cases of sporadic AD and in five cases of familial AD including one in which the APP717 Val-->Ile mutation was present. Beta A4 protein load, as measured by square microns of immunoreactivity per square millimetre of cortex, was similar in the frontal and temporal isocortex in both sporadic and familial AD. There was greater variation in beta A4 protein load in subfields of the hippocampus but these differences were not significant between sporadic and familial cases. In the case with the APP717 Val-->Ile mutation. Beta A4 protein load in isocortex was greater than the mean for familial and sporadic cases of AD but less than the most severe cases of beta A4 protein deposition which were found in sporadic AD. In addition, the case with the APP717 Val-->Ile mutation has the same cytoskeletal pathology as sporadic cases of AD. The mechanism by which normal and mutant APP is processed to produce amyloidogenic fragments remains to be determined. PMID- 8474687 TI - Evidence for the localization of haemopexin immunoreactivity in neurones in the human brain. AB - Haemopexin is a 60 kDa serum glycoprotein responsible for the transport of haem to tissues such as liver, by receptor-mediated endocytosis, in an analogous manner to the iron transport protein transferrin, with recycling of intact haemopexin. The immunocytochemical distribution of haemopexin has been investigated, using a monospecific polyclonal antiserum to human haemopexin, in human brain. Neurones in all the brain regions studied showed immunostaining of the soma, axons and dendrites. A few scattered glial cells exhibited positive immunostaining. Oligodendrocytes and choroid plexus epithelial cells lacked haemopexin immunoreactivity. Thus, haemopexin is present within neurones and we propose that this protein may play an important role in haem transport for neuronal iron homeostasis. PMID- 8474688 TI - Afferent and efferent connections of the thalamic eminence in the axolotl, Ambystoma mexicanum. AB - Afferent and efferent connections of the thalamic eminence of the axolotl were determined using the fluorescent compound DiI as a tracer. The thalamic eminence is connected reciprocally with a number of telencephalic and diencephalic areas, particularly with the medial pallium, the amygdala and the preoptic region. Efferent connections are widespread throughout the ipsilateral diencephalon. These findings are discussed in relation to the homology of this nucleus, especially its homologue in agnathan brains. PMID- 8474689 TI - Coexistence of c-Fos and glucocorticoid receptor immunoreactivities in the CRF immunoreactive neurons of the paraventricular hypothalamic nucleus of the rat after acute immobilization stress. AB - By means of triple immunofluorescence procedures the codistribution and coexistence of glucocorticoid receptor (GR), c-Fos and corticotropin-releasing factor (CRF) immunoreactive (IR) nerve cell profiles have been analyzed within the paraventricular hypothalamic nucleus at various rostrocaudal levels following acute immobilization stress (2 h) in the male rat. One population of CRF IR neurons is shown to contain both nuclear GR and c-Fos immunoreactivities following the stress, while another contains GR immunoreactivity alone. These results indicate heterogeneities among parvocellular CRF paraventricular hypothalamic nerve cell populations in the response to acute immobilization stress. PMID- 8474690 TI - Rats do not experience cortical or hippocampal spreading depression as aversive. AB - Cortical spreading depression (SD) may produce some symptoms of the aura of classical migraine but it is less probable that it can account for the headache. The aversiveness of SD was examined in unanesthetized rats. In Exp. 1, rats with implanted cortical cannulae were confined in the dark compartment of the step through apparatus and repeated waves of SD were elicited in one hemisphere. After two such training sessions the rats did not evince passive avoidance of the compartment associated with cortical SD. In Exp. 2, thirsty rats with implanted hippocampal electrodes were trained to drink from two different spouts A and B. Hippocampal SD was elicited when the animal was drinking from spout A but not from spout B. Drinking was interrupted shortly after appearance of the SD wave and gradually recovered over the subsequent 10 min, but up to ten spout A-SD pairings did not change the animal's preference for spout A. It is concluded that cortical or hippocampal SD has no immediate or delayed aversive consequences. PMID- 8474691 TI - Dissociation of HSP70 and HSC70 heat shock mRNA inductions as an early biochemical marker of ischemic neuronal death. AB - A significant dissociation of HSP70 and HSC70 heat shock mRNAs after a 10-min transient forebrain ischemia in gerbil was found only in the hippocampal CA1 neurons which eventually die after the initial ischemic insult, while other hippocampal neurons such as the dentate granule and the CA3 cells which survive ischemia expressed both mRNAs cooperatively. The dissociation was observed as early as after 8 h of reperfusion, a period far shorter than 3-4 days, when the cell death becomes pathologically evident. Thus, the dissociation may serve as a set of early biochemical markers for ischemic neuronal cell death. PMID- 8474692 TI - Alterations in vasopressin and oxytocin messenger RNA in the rat supraoptic nucleus during dehydration-rehydration evaluated by in situ hybridization and northern blotting. AB - Male rats were deprived of water for 5 days, and then given water ad libitum for 3, 7, 10 or 14 days. Plasma osmolarity returned to normal in less than 3 days, while pituitary vasopressin (AVP) and oxytocin (OXT) only returned to control levels after 14 days. Sections of the supraoptic nucleus (SON) were hybridized with 35S-labelled cDNA (OXT) or oligonucleotide (AVP) probes. Relative AVP and OXT mRNA contents were quantitated by counting the number of silver grains on a large standard area of the SON, then extrapolating this value to the volume of the whole SON (deduced from surface areas of all the sections). Dehydration significantly enlarged the volume of the SON (x 1.54) and increased the AVP and OXT mRNAcontent (x 2). During rehydration, both SON volume and density of silver grains were higher than normal for at least 7-10 days, although levels started to fall by day 3. The distribution of individual cells according to their silver grain densities remained unimodal during the dehydration-rehydration sequence with an extension, then a return to normal of the distribution range. Maximum sizes of AVP and OXT mRNAs on Northern blots of RNAs extracted from 5 pooled SONs were observed on dehydration day 5. The size of these species fell progressively, reaching control values by rehydration day 14. We conclude that during rehydration, at a time when most of the putative inducers of gene transcription are no longer activated, the peptidergic deficit was accompanied by an increased level of AVP and OXT mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474693 TI - Noxious mechanical stimulation of the hind paws of the anaesthetized rat fails to elicit release of immunoreactive beta-endorphin in the periaqueductal grey matter. AB - As a test of the hypothesis that an animal responds to a severe peripheral painful stimulus by a central release of beta-endorphin, antibody microprobes were inserted stereotactically into the midbrain of urethane anesthetized rats. These microprobes bore antibodies to beta-endorphin immobilized to their outer surfaces. While microprobes were in the brain for periods of 10 to 30 min either no stimulus was delivered or alligator clamps were applied to both hind paws. Microprobes were then incubated with 125I-beta-endorphin. Quantitative image analysis of microprobe autoradiographs showed no differences between the no stimulus and noxious-stimulus groups. Thus these experiments found no evidence for beta-endorphin release following a severe peripheral painful stimulus. PMID- 8474694 TI - Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats. AB - The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension. PMID- 8474695 TI - Projections from the commissural subnucleus of the solitary tract onto catecholamine cell groups of the ventrolateral medulla. AB - Efferent projections of the commissural subnucleus of the solitary tract (COM) to the ventrolateral medulla were studied in the cat using anterograde labeling with biocytin combined with dopamine beta-hydroxylase immunohistochemistry. COM neurons were observed to send their axons densely to the areas of distribution of respiration-related neurons in the ventrolateral medulla, e.g. ventral respiratory group, Botzinger complex. Axon terminals from COM neurons were further found in the areas of distribution of catecholamine neurons (C1 and A1 cell groups), that were distributed in the close vicinity of the reported respiration-related areas in the ventrolateral medulla. Putative synaptic contacts of axon terminals from COM neurons with catecholamine neurons were often observed in the C1 area. PMID- 8474696 TI - Reduced increase in plasma renin activity on water-deprivation in blind hereditary microphthalmic rats. AB - We compared the plasma renin activity (PRA) before and after 24-h water deprivation in blind hereditary microphthalmic rats and Donryu rats. In the congenitally blind rats with a morphologically abnormal suprachiasmatic nucleus (SCN), hypovolemia induced significantly less elevation of the PRA and significantly more increase in the hematocrit value than in normal rats. The changes after water-deprivation in the blind rats were quite similar to those reported in rats with SCN lesions. However, the free-running circadian rhythms persisted in these blind rats, whereas those in rats with SCN lesions were completely eliminated. Thus, it is likely that SCN cells are involved in regulation of the PRA, and that if this is the case these cells are different from those containing the circadian pacemaker. PMID- 8474697 TI - Alterations in mitochondrial branched-chain amino acid metabolism in brain in acute hyperammonemic states. AB - Production of 14CO2 and [14C]branched-chain keto acids (BCKA) was determined from [U-14C]branched-chain amino acids along with the activities of branched-chain amino acid transaminase (BCAA-T) and branched-chain keto acid dehydrogenase (BCKA DH) in mitochondria isolated from the cerebral cortex of normal and hyperammonemic rats. Results indicated that the production of CO2, but not of keto acids, was suppressed while the activities of BCAA-T and BCKA-DH were not adversely affected in the mitochondria of hyperammonemic rats. Suppression in the oxidation of BCAA in hyperammonemic states was found to be due to increased efflux of BCKA from mitochondria. PMID- 8474698 TI - Age-related changes in human muscarinic acetylcholine receptors measured by positron emission tomography. AB - The effects of age on the binding parameters of [11C]N- methyl-4 piperidylbenzilate ([11C]NMPB), a specific muscarinic cholinergic receptor ligand, were studied. Eighteen healthy male volunteers (18-75 years old) participated. Regional radioactivity in the brain was followed for 60 min by positron emission tomography (PET). Uptake of [11C]NMPB continuously increased in all brain areas with the exception of the cerebellum. For the quantification of receptor binding, a compartment model, in which radioactivity in the cerebellum was used as an input function, was used. The binding parameter, K3, of muscarinic acetylcholine receptors in eight brain regions (pons, hippocampus, frontal cortex, striatum, temporal cortex, thalamus, occipital cortex, parietal cortex) showed an age-related decrease of about 45% over the age range. PMID- 8474699 TI - Limited but evident protective effects of MK-801 and pentobarbital on neuronal damage following forebrain ischemia in the gerbil under normothermic conditions. AB - The purpose of this study was to examine the protective effects of an N-methyl-D aspartate receptor antagonist, MK-801, and pentobarbital against neuronal damage in a global ischemia model under controlled body temperature. Gerbils were subjected to 3 and 5 min of bilateral common carotid artery occlusion. MK-801 (1 and 5 mg/kg, i.p.), administered 30 min before ischemia, significantly attenuated the degeneration of hippocampal CA1 pyramidal cells after 3 min of ischemia in a dose dependent manner, but had no such effects after 5 min of ischemia. Pentobarbital (40 mg/kg, i.p.) also protected against CA1 damage after 3 min of ischemia but not after 5 min of ischemia. Thus, we confirmed the protective effects of these agents under normothermic conditions, although these effects were limited to shorter periods of ischemia. PMID- 8474700 TI - Variations in membrane potential trajectory of post-inspiratory neurons in the ventrolateral medulla of the cat. AB - In decerebrate cats, intracellular recordings were made in 124 expiratory neurons displaying either a plateau-phase of depolarization during post-inspiration or a steadily decrementing depolarization throughout expiration. Both groups consisted of vagal motoneurons and non-antidromically activated neurons. Five neurons were antidromically activated by both vagal and spinal cord stimuli. The pattern in membrane potential was changed from one type to another either spontaneously or experimentally. The present results suggest that the variable appearance of the membrane potential trajectory does not represent the different functional category of bulbar post-inspiratory neurons. PMID- 8474701 TI - Obesity and body fat distribution in New Zealanders: a pattern of coronary heart disease risk. AB - AIMS: To describe the prevalence of obesity and the body fat distribution of New Zealanders. To discuss this in the context of the coronary heart disease risk. METHODS: Body weight and height, body mass index (BMI), waist:hip ratio (WHR) and six skinfold measurements were determined for 3204 randomly selected New Zealanders who responded to an invitation to a health check (response rate 56%). RESULTS: In the study sample BMI generally increased with age. Fifty five percent of men and 38 per cent of women aged 18-64 had a BMI exceeding 25, and of these 13 per cent and 10 per cent were obese (BMI > 30). WHR was greater in men than in women of all ages, and a third of the men and a quarter of the women had values exceeding 0.9 and 0.8 respectively. Central skinfold measurements (subscapular, suprailiac and abdominal) were lowest in young men, but rose markedly with age and were similar to women above age 35. Limb skinfolds were lower in men. CONCLUSIONS: This survey indicates that a large percentage of New Zealanders are overweight or obese and their excess body fat tends to be centrally distributed, especially in men. Obesity is thus a significant health problem in New Zealand. PMID- 8474703 TI - Measuring consequence of disease. PMID- 8474702 TI - Methicillin resistant Staphylococcus aureus (MRSA) in New Zealand 1988-90. AB - AIMS: To survey methicillin-resistant Staphylococcus aureus (MRSA) in New Zealand during the three years 1988-90. METHODS: Isolates and accompanying epidemiological data referred and reported to the New Zealand Communicable Disease Centre were analysed. RESULTS: MRSA was isolated from 255 persons, 235 patients and 20 healthcare staff, over the three years. The majority (84%) of persons were, or were recent, hospital patients or staff. Among hospital patients, males and patients aged 0 to 14 years were more likely to have MRSA. While most (88%) of the 145 strains identified occurred sporadically, three caused large outbreaks each involving more than 20 people. A third of the strains originated overseas, most commonly Australia or one of the Pacific Islands. The rate of MRSA isolation was higher in the North Island than the South Island. Two thirds of the MRSA had only a low level of methicillin resistance and were not multiresistant. CONCLUSIONS: MRSA continues to be isolated only infrequently in New Zealand and has not become endemic in our hospitals. PMID- 8474704 TI - Hospital associated costs of treating patients with AIDS. AB - AIM: To determine the hospital associated costs of caring for patients with AIDS. METHOD: We reviewed the notes of all 40 patients with AIDS admitted to the Auckland Hospital infectious disease unit during 1988. We used the resource utilisation system (RUS) to determine costs. RESULTS: Costs were maximal in the month of diagnosis of AIDS (ca $3500/month), falling thereafter to ca $1000/month until they rose again in the last months of life. Total costs were dominated initially by inpatient costs but subsequently by the costs of medicines. CONCLUSION: The hospital costs associated with the care of AIDS patients are not spaced evenly throughout the illness. Extended life will not increase costs proportionately. PMID- 8474705 TI - Induction of labour with prostaglandin E2; a prospective audit. AB - AIMS: To perform a prospective audit of inductions of labour using prostaglandins to assess the protocols for induction in use at that time. METHODS: Data on 123 patients was obtained over a six-week period. Information regarding gestation, indication for induction and relevant details of labour and delivery were obtained. RESULTS: There were three (2.5%) patients with hyperstimulation and six (5%) with failed induction. Nulliparous patients with an unfavourable cervix had an increased caesarean section rate (29%) and a prolonged induction to delivery interval (mean: 27 hours). CONCLUSIONS: The protocols for induction of labour using prostaglandins presently in use appear to be safe although staff need to be well informed about the management of hyperstimulation should it occur. Further audit of indications for induction of labour and of the caesarean section rate is required. PMID- 8474706 TI - Prescribing for childhood asthma in the Wellington area: comparison with international guidelines. AB - AIMS: An international paediatric asthma consensus group has outlined the rational approach to the treatment of childhood asthma. We have examined the prescription of asthma treatment to children in Wellington to assess to what extent these guidelines have been adopted by general practitioners. METHODS: During the period 1 May-11 June 1991, the prescriptions for 228 asthmatic children, dispensed at 30 randomly selected pharmacies in the greater Wellington area, were reviewed. RESULTS: Eighty-four per cent of the children were prescribed beta 2 adrenoceptor agonists. Of these, 80% of those under five years, and 27% over five years of age, received these agents by the oral route. In almost half, these drugs were prescribed on a regular basis. Fifty-two per cent of patients were prescribed some form of antiinflammatory therapy (inhaled or oral steroids, ketotifen or sodium cromoglycate). Only 2% received sodium cromoglycate. CONCLUSION: Although approximately half of these children received some form of antiinflammatory therapy, the minimal use of sodium cromoglycate, and high frequency of regular scheduled beta 2 adrenoceptor agonist use, suggests that the guidelines for asthma management in children may not have been widely adopted by primary care physicians in Wellington. PMID- 8474707 TI - Complications of termination of pregnancy: a retrospective study of admissions to Christchurch Women's Hospital 1989 and 1990. AB - AIMS: To review the admissions to Christchurch Women's Hospital with complications of termination of pregnancy. To estimate complication rates from Christchurch institutions and compare this with the international literature. METHODS: Relevant admissions were recorded by admitting staff. The hospital notes were retrospectively analysed. The complication rates were estimated from Christchurch termination rates in the study period. RESULTS: In 1989 and 1990 there were 2879 terminations of pregnancy performed in Christchurch. There were 167 admissions with complications. There was an admission rate of 5.8% and a curettage rate of 4.8%, 2.9% were confirmed to have retained products of conception. 0.47% required laparoscopy or laparotomy, 0.1% required blood transfusion. There was an increased rate of complications after 14 weeks. CONCLUSION: Admission rates in Christchurch are similar to those in some studies, others suggest that with improved technique and ideal follow up assessment readmissions could be reduced. PMID- 8474708 TI - Slow acting antirheumatic drugs in rheumatoid arthritis. PMID- 8474709 TI - Emotional health, cancer and heart disease. PMID- 8474710 TI - Sexually transmitted diseases and HIV testing. PMID- 8474711 TI - Video game induced generalised epileptic convulsion. PMID- 8474712 TI - Meningococcal immunisation. PMID- 8474713 TI - Folic acid and neural tube defects. PMID- 8474714 TI - The value of cancer treatment. PMID- 8474715 TI - Milkers' chilblains. AB - AIM: To report on the clinical features, causative factors, management and preventive measures for chilblains of the hands occurring in milkers in the Waikato area of New Zealand. METHODS: A review was made of the case notes of all patients with milkers' chilblains seen in dermatological practice in Hamilton over a ten year period ending in 1991 and follow up interviews were made. RESULTS: Eleven milkers were seen with distinctive, at times disabling, seasonally-recurring chilblains of the hands. In most patients the chilblains had developed early in their milking careers. Difficulty was experienced by both the patients and their doctors in recognising the nature of their skin condition. Sunlight aggravation of the lesions was a feature. In most patients treatment of the presenting episode required time off work and in several patients significant scarring resulted. Three patients left dairying because of the chilblains. Those who continued received preventive advice but four patients had further lesions in subsequent years although these were mild. CONCLUSIONS: Milkers' chilblains are uncommon but some cases are misdiagnosed and milder cases may not present for medical attention. Morbidity can be significant. Preventive measures are helpful but their effect may be limited by the difficulty of wearing gloves for milking. The vasodilator nifedipine is suggested as a prophylactic therapy for these patients. PMID- 8474716 TI - Is it easy collecting ethnicity data in general practice? PMID- 8474717 TI - Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls. AB - AIMS: To investigate the possibility of a correlation between the percentage of nondiscocytic erythrocytes and muscle fatiguability in subjects with the symptom of chronic tiredness. METHODS: Sixty nine volunteers suffering from persisting or intermittent tiredness and 72 healthy controls provided 3-drop samples of venous blood for red cell shape analysis before and after inducing fatigue in the trigger finger muscles by repeatedly pulling the trigger of an antique revolver. Elapsed time and the number of pulls were recorded. A work index was calculated from the number of trigger pulls divided by the time in seconds then multiplied by the number of trigger pulls. RESULTS: Subjects with tiredness had fewer discoid cells (males 62.5% vs 69.2%, p = 0.029; females 65.8% vs 71.8%, p = 0.002) than controls. They also had fewer trigger pulls (males 62.3 vs 84.0, p = 0.003; females 29.5 vs 36.8, p = 0.042) and lower "work indices" (males 75.6 vs 104.7, p = 0.001; females 26.1 vs 39.6, p = 0.001) than controls at the first trigger pulling. After 5 minutes rest the number of trigger pulls for males was fewer than the controls (56.0 vs 64.2) but the difference was not significant, but the female values (24.3 vs 33.2) were significantly different (p = 0.008). Work indices for both sexes were significantly different from controls (males p = 0.020, females p = 0.001). CONCLUSIONS: The association of increased nondiscocytes and impaired muscle function could indicate a cause and effect relationship. This would be in agreement with the physiological concept of fatigue as a consequence of inadequate oxygen delivery. PMID- 8474718 TI - The management of peptic ulceration. PMID- 8474719 TI - Noninsulin dependent diabetes mellitus. PMID- 8474720 TI - Cancer rates. PMID- 8474721 TI - Direct antigen test for group A streptococcal pharyngitis. PMID- 8474722 TI - Suicide in New Zealand 1950-85. PMID- 8474723 TI - Fluoridation. PMID- 8474724 TI - Outcome of adults with acquired immunodeficiency syndrome in Auckland 1983-9. AB - AIMS: To assess the survival of Auckland residents diagnosed with AIDS between 1983 and 1989. METHODS: Retrospective case review RESULTS: Sixty nine Auckland residents were diagnosed with AIDS between 1983 and the end of 1989, and were cared for by the infectious disease unit, Auckland Hospital. The overall median survival was 289 days with 48% and 20% surviving at one and two years respectively. Survival was longer among those who were infected through homosexual contact, were younger, and not known to the infectious disease unit prior to the diagnosis of AIDS. Although survival was longer for those diagnosed in 1988 compared to earlier years, it was shorter again for those diagnosed in 1989. Pneumocystis carinii pneumonia, the AIDS defining condition in 63.8% of people, was found less frequently in 1989, and overall was associated with a longer survival than most of the other AIDS-defining diagnoses. A quarter of the people were not known to be infected with HIV prior to the AIDS-defining condition. CONCLUSION: In New Zealand, as in other countries, changes in treatment strategies of people with HIV infection may impinge on the survival of people with AIDS. PMID- 8474725 TI - Serum lipid levels in a New Zealand multicultural workforce. AB - AIMS: To examine ethnic variations in serum lipid levels and to determine whether lipids are related to lifestyle variables in a New Zealand multicultural workforce. METHODS: Fasting blood samples were collected from 5671 employed people for determination of serum total and HDL cholesterol, triglycerides, and LDL cholesterol. Individual exposures over the previous three months to smoking, alcohol, leisure time physical activity were recorded, and weight and height were measured to calculate body mass index (BMI). RESULTS: Maori and Pacific Islanders had lower age-adjusted total and LDL cholesterol levels than Europeans, and these differences were increased by controlling for BMI. In contrast, age-adjusted mean (SE) HDL cholesterol levels were also lower in Maori (men = 1.17 (0.02); women = 1.38 (0.03) mmol/L) and Pacific Islanders (men = 1.17 (0.01); women = 1.30 (0.02) mmol/L) compared with Europeans (men = 1.20 (0.01); women = 1.47 (0.01) mmol/L), but when BMI, smoking and other variables were controlled, levels were significantly higher in Maori and Pacific Islanders. With serum triglycerides, the pattern was not consistent in Maori and Pacific Islanders. Age-adjusted mean levels in Maori (men = 2.25 (0.07) mmol/L; women = 1.53(0.07) mmol/L) were significantly higher (p < 0.05) than in Pacific Islanders (men = 1.82 (0.06); women = 1.34(0.05) mmol/L) of the same sex. After controlling for BMI and other variables, triglyceride levels were also significantly lower in Pacific Islanders than in Europeans and Asians. BMI and smoking were positively associated with total and LDL cholesterol and triglycerides, and negatively with HDL cholesterol, after controlling for alcohol and physical activity. CONCLUSION: Lifestyle risk factors, particularly BMI and smoking, are strongly related to serum levels of all major lipids. Ethnic variations in coronary heart disease mortality rates in New Zealand are more consistent with ethnic variations in triglycerides than with variations in the other serum lipids. PMID- 8474726 TI - Attitudes to reducing violence towards women: punishment or prevention? AB - AIM: To investigate the attitudes of abused and nonabused women to reducing physical and sexual violence in the community. METHOD: A random community sample of 3000 women was surveyed by postal questionnaire as part of the Otago Women's Health Survey. Seventy three percent (n = 1663) of those under 65 replied. As well as demographic, mental health and abuse information, responses to the question "what steps would you like to see taken to reduce the incidence of sexual and physical harm to women and children?" were analysed. RESULTS: Education was the most favoured approach to reducing violence in the community, followed by increased punishment of the offender. Women who had experienced sexual abuse, particularly as children, were more likely to advocate measures other than punishment. Rural women, those without formal qualifications and those who were not abused were more likely to advocate increased punishment, or made no comment. CONCLUSION: The finding that victims of sexual assault were likely to report a preference for prevention over punishment highlights the importance of representing the views of the community which appear to be at variance with more extreme views publicized in the media. PMID- 8474727 TI - Radiofrequency ablation of anomalous cardiac pathways: initial experience. AB - AIM: To describe the initial experience of radiofrequency ablation of anomalous cardiac pathways in patients with supraventricular tachycardias. METHODS: A total of 10 patients with refractory supraventricular tachycardias mediated by anomalous cardiac pathways underwent electrophysiological assessment and attempted pathway ablation. RESULTS: Seven patients with left free wall atrioventricular pathways (two concealed) and two patients with dual atrioventricular nodal pathways had successful pathway ablations and have had no recurrence of arrhythmia. One patient with a concealed posteroseptal atrioventricular pathway was not able to be ablated. All patients tolerated the initial procedure well, but one developed pericarditis later. CONCLUSION: Radiofrequency ablation promises to be an important new technique for the management of patients with anomalous cardiac pathways and supraventricular tachycardias. Our initial experience has been favourable and comparable to other reported series with a high success rate and infrequent complications. PMID- 8474728 TI - Inequalities in health and redefining values. PMID- 8474729 TI - General practitioners acceptance of the validity of chronic fatigue syndrome as a diagnosis. AB - AIM: To identify whether general practitioners accept the validity of a diagnosis of chronic fatigue syndrome (CFS). METHOD: An anonymous questionnaire was sent out to 98 general practitioners in Otago. RESULTS: The clinical validity of chronic fatigue syndrome was accepted by 74 (90%); 57 believed they had sufficient knowledge about the condition to make a differential diagnosis; 72 indicated they had had patients with chronic fatigue syndrome in the past; 62 currently had patients; there is a minimum prevalence rate of 167/100,000 in the general practice population; 83 replies were received. CONCLUSION: The 90% acceptance rate of chronic fatigue syndrome as a clinically valid diagnosis suggests that amongst the Otago general practitioners the controversy had receded. The low numbers suggest that they are on the conservative end of the diagnostic spectrum. PMID- 8474730 TI - The results of tubal surgery in the treatment of infertility in Wellington 1986 90. AB - AIMS: To audit the outcome of tubal surgery performed in Wellington between 1986 90. To establish the appropriate indications for tubal surgery in terms of likely benefit. To compare benefit with other treatment modalities namely in vitro fertilisation. METHODS: Data obtained from hospital patient notes, theatre records and personal communication. RESULTS: There were 71 patients, 67 of whom had been adequately followed up. The total pregnancy rate was 41.8% with an overall term pregnancy rate of 29.8%. The success rate was highest with proximal tubal occlusion and worst for distal disease and endometriosis. CONCLUSION: The outcome of the audit is consistent with results worldwide. Tubal surgery allows for natural conception and more than one pregnancy can be conceived as a result. It should be considered the first line treatment for proximal tubal disease and fimbrial adhesions. In vitro fertilisation however should be offered to those with severe distal disease and severe endometriosis. PMID- 8474731 TI - The distribution of household expenditures on health care. AB - AIMS: To find out whether New Zealand household expenditures on health care services vary according to the income of the household. To compare expenditures on health care in 1987 with 1991. METHODS: Information about household income and expenditure on health services was obtained from the Department of Statistics annual household expenditure and income surveys for the 1987 and 1991 financial years. Four categories of health expenditure were examined: general practitioner fees, dental fees, optician and optometrist fees, and spending on all health services combined. RESULTS: Spending on health care is unequally distributed across income groups. In particular, the highest income households spend six times as much on dental care as the lowest income households. The difference between high and low income households in the amount spent on all health services was greater in 1991 than in 1987. In 1991 high income households spent 3.6 times as much on health services as low income households, compared with three times as much in 1987. CONCLUSIONS: High income households spend substantially more on health care than do low income households. Households appear to assign a higher priority to medical care than dental care, although this may reflect the lack of any state subsidy on adult dental care. PMID- 8474732 TI - Intrathecal baclofen for the management of severe spasticity. PMID- 8474733 TI - Medicine at the fringes. AB - Until the new Act is in operation, and assuming it has strong and clear sections covering competence, the Medical Council of New Zealand is left with the need to manage unorthodoxy as a form of misconduct unless there is a mental health problem. Charges of misconduct unless there is a mental health problem. Charges of misconduct may arise of there is: harm to patients inadequate information and consent including false representation of the theoretical base of diagnostic method or management, or the training of the doctor, short cuts in the standard methods of diagnosis with the use of unproven and unrecognised methods, treatment programmes that are inappropriate, unjustified, unproven or unsupported by a substantial body of opinion, or that omit consideration if orthodox methods. exploitation in terms of securing patients, financial gain and inadequate aftercare. PMID- 8474735 TI - Cot death. PMID- 8474734 TI - Guidelines for detection and management of dyslipidaemia. Scientific Committee of the National Heart Foundation of New Zealand. PMID- 8474736 TI - Health reforms. PMID- 8474737 TI - New Zealand Multiple Birth Association. PMID- 8474738 TI - ACC and the carpal tunnel syndrome. PMID- 8474739 TI - Occupational asthma. PMID- 8474740 TI - Cholesterol lowering trials and the theory of atherosclerosis. PMID- 8474741 TI - AIDS 1992. PMID- 8474742 TI - Medical Practitioners Disciplinary Committee: inadequate antenatal management. PMID- 8474743 TI - Hospital mergers may threaten access to tubal ligations. PMID- 8474744 TI - Liability issues for trauma nurses. PMID- 8474745 TI - Informed consent: cautious, calculated candor. PMID- 8474746 TI - Technology: nursing the system. A nursing management minimum data set. PMID- 8474747 TI - Health reform: the shape of things to come. AB - To understand the various legislative initiatives at state and national levels, one must know what questions to ask and what issues are raised by each question. The questions are: (1) How much shall we reform the system? (2) How quickly shall we reform the system? (3) How shall we fund the system? and (4) How shall we organize or reorganize the system? If the complex issues these questions raise are dealt with quickly, boldly and fairly, meaningful health reform will be passed in 1993 and phased in over the next five to seven years. PMID- 8474748 TI - Measuring variations in nursing care per DRG. AB - A state nurses' association, a state department of health and a consulting agency collaborate annually in a special nursing study to develop appropriate measures of the relative variation in nursing care associated with each DRG. This activity provides a mechanism for professional nurses and the nursing profession to have direct input into a state's reimbursement methodology. This methodology is unique in the nation and may serve as an important prototype for nurses in other states who are seeking recognition of nursing care and services in the DRG reimbursement system. PMID- 8474749 TI - Clinical pathway development: the Overlake Model. AB - Overlake Hospital Medical Center has developed a multi-faceted Care Management Model to improve clinical and fiscal outcomes for selected patient populations. The Clinical Pathway Component of this model has been applied to high-volume, high-loss DRG groups. Success of the program can be attributed to the unique multidisciplinary problem solving approach, team building and a focus beyond the inpatient hospital stay. PMID- 8474750 TI - Salary compression of nursing managers. AB - An American Hospital Association survey has shown that rapid escalation of staff nurse salaries and benefits, in the wake of local and national shortages, has pushed clinical wage structures beyond those that determine the salaries of nurse managers and administrators. This leads to difficulty both in recruitment and retention of these key personnel. In this hospital, attrition of nurse managers into clinical positions has ceased. Their approach makes nurse managers eligible for differentials in addition to a modest economic incentive for assumption of managerial responsibilities. PMID- 8474751 TI - Toward successful compliance with JCAHO standard NC.1. AB - Recommendations resulting from a JCAHO survey can be a true blessing as they force nursing departments to assess critically their professional practice and documentation systems. Systematic preparation, begun at least two years prior to the survey, includes Nursing Administration, a Nursing Documentation Task Force and all staff nurses. Educational consultants assigned to each unit bring nurses up-to-date on nursing process and nursing diagnosis. Mock surveys and cross training in chart review prepare staff nurses for confident participation in the accreditation process. PMID- 8474752 TI - Of mythspinners and mapmakers: 21st century managers. AB - The entire character of human experience is unfolding within an epochal change event as civilization shifts away from the Industrial Age. The U.S. healthcare system, rocked by the same dizzying rate of change, will play a pivotal role in the emergence of a new social contract. The coming transformation will require a revolutionary change in leadership style: the nursing manager really becomes a change agent--challenging, questioning the status-quo and creating an atmosphere where self-directed activities, workplace partnerships and shared clinical outcomes become the norm. PMID- 8474753 TI - Alliance for destiny: education and practice. AB - As the whole context of nursing continues to change radically in the face of unmet societal needs, nothing short of total revolution will suffice. Nurses must take control of nursing practice and be critical of the nation's inadequate "sick care" system in order to effect sweeping changes in the scope, availability and efficacy of healthcare in the U.S. To do this requires an acknowledgment that true nursing education cannot exist without nursing practice. The transformation of curriculum must center on caring, which characterizes what nurses really do in a medically dominated system focused exclusively on curing. PMID- 8474754 TI - Selecting an information system. AB - Use of new technology can improve productivity without compromising staff nurse time at the bedside. At Borgess Medical Center an interdisciplinary committee co chaired by nurses analyzed the information system and documentation procedures and developed a plan approved by administration. This resulted in establishment of both a sophisticated point-of-care system and an ongoing patient care informatics committee to further coordinate automation throughout the hospital. PMID- 8474755 TI - Resource management education: an imaginative approach. AB - "Outcomes," a resource management game, promotes case management philosophies and strategies. This unique approach to teaching offsets the nurses' fear of change by learning in a relaxed environment. PMID- 8474756 TI - When push comes to shove... PMID- 8474757 TI - Productivity presented graphically. AB - Tools used in collecting data on nursing workload focus on standards of care, time and motion studies and patient care requirements. Since no one tool can measure adequately the work of nursing, the number of personnel required to fill patient needs is difficult to determine. Thus, a tool with long-term predictive ability can be valuable in assisting nursing administrators to determine staffing requirements. Any nursing department with a computerized database which can produce variance can develop long-term graphical representations of staffing like that described in this paper. PMID- 8474758 TI - Managing humor: when is it funny--and when is it not? AB - A survey of Canadian hospital nurses revealed they differentiate among situations in which humor would improve staff working relations. This intimates humor may be suitable for reducing nursing stress in some situations but not others. PMID- 8474759 TI - Prediction and early diagnosis of preterm labor: a critical review. PMID- 8474760 TI - [The prevention of congenital developmental anomalies in rats]. AB - Preventive administration of Eleutherococcus XXX extract during prenatal and pre embryonic periods of development prevents embryotoxic effect of subsequent treatment of pregnant rats with ethanol and sodium salicylate. Eleutherococcus abolishes embryotoxic and teratogenic effects of ethanol manifested against the background of experimental syndrome of iron deficit in pregnant females. Mechanism of its antiteratogenic action is probably based on stimulation of cell detoxification mechanisms, increase in energy potential of cells, as well as on stabilization of structural and functional state of cell membranes. PMID- 8474761 TI - [An ultrastructural analysis of the cells of the outer root sheath of the hair follicles in mice of the wellhaarig mutant strain]. AB - Ultrastructure of cells of the outer root sheath (ORS) of the guard hair follicles from the dorsal part of the body of 12-day old we/we and +/+ mice was studied. Changes observed in the ultrastructure of ORS cells in mutant mice included greater vacuolization of the cytoplasm and damaged structure of mitochondria accompanied by the absence of crisis. Many cells of the ORS outer layer in hair follicles of we/we and +/+ mice showed electron-dense outgrowths oriented axo-proximally which suggests their possible involvement in transportation of the hair, by contraction of these outgrowths, to the skin surface. Possible mechanisms of hair growth in view of these data are discussed. PMID- 8474762 TI - [Gametogenesis and zygote and ookinete formation in some haemoproteid species (Haemosporidia: Haemoproteidae) of birds in vitro]. AB - Observations were made through examination of thin blood films which were prepared at appropriate intervals from citrated fresh blood of infected birds. The comparative description of gametogenesis, zygote and ookinete formation of Haemoproteus tartakovskyi, H. belopolskyi, H. fringillae, H. pallidus under the light microscope is given for the first time. This process has a general pattern for all investigated haemoproteid species. It is shown that macrogametocyte has been transformed directly to macrogamete without forming a residual body, as it was noted by Desser (1972) for H. (= Parahaemoproteus) velans. The most informative signs, which can be used for haemoproteid systematics, were determined. Among them microgamete length, zygote structure, morphological features of developing ookinete as well as the rate of ookinete formation can be pointed out first of all. H. pallidus microgametes are twice shorter than H. tartakovskyi, H. belopolskyi, H. fringillae ones. A large clear vacuole is formed in zygote of H. fringillae only. The majority of diagnostic features has the developing ookinetes. On the basis of ookinetes morphology the investigated species of haemoproteids can be determined easily. There were clear differences between haemoproteid species on the rate of ookinete formation. The ookinetes of H. belopolskyi and H. fringillae are formed for about 12 times more slowly than H. pallidus ones, and for about 6 times more rapidly than H. tartakovskyi ones. The peculiarities of gametogenesis, zygote and ookinete formation under the stable conditions in vitro can be used as usefull additional signs for determination of haemoproteid species. PMID- 8474763 TI - [The surface of cysts and excysted metacercariae of Opisthorchis felineus studied by scanning electron microscopy]. AB - The structure of cysts of metacercariae of O. felineus has been analyzed. The cyst structure appears to have folds, pores and spherical formations providing for larval homeostasis. On the tegument of metacercariae thorns are arranged in staggered order. They represent 3 to 6 finger-shaped structures. The thorns and tegument excreta are secreted. On the surface of the parasite there are single and group sensory cupola-shaped and conoid papillae which make a chain around the mouth sucker. Polymorphism is revealed in the opisthorchis metacercariae structure. PMID- 8474764 TI - [The effect of lower cestodes (Pseudophyllidea) on the vital activity of 2-year old grass carp]. PMID- 8474765 TI - [The occurrence of unusual chaetotaxy in III--IV instar larvae of blood-sucking mosquitoes from the genus Aedes]. AB - Larval material on the Aedes mosquitoes of the complex punctor (Far East expeditions in 1976-1980) was compared to material preserved in the Zoological Institute, Academy of Sciences of Russia. 6 types of aberrations (presence absence of accessory hairs on the surface of siphon, their parity, etc.) were found. The individual variability and absence of diagnostic validity of these accessory hairs are suggested. PMID- 8474766 TI - [The antigenic properties of the larvae of Oedemagena tarandi (Hypodermatidae)]. PMID- 8474767 TI - [Diphyllobothrium skriabini sp. n. (Cestoda: Diphyllobothriidae)--a parasite of the bearded seal (Erignathus barbatus Erx.)]. AB - A new species of cestodes is described from the intestine of Erignathus barbatus Erx. The species differs from the other members of the genus in the shape of scolex, the character of strobilation and in many other characters. Data are given on its morphological variability in different waters: the Greenland and East Siberian Seas, the Bering Strait. Two subspecies, D. s. europeum and D. s. asiaticum, are erected. The species is named in honour of Professor A. S. Skriabin, one of the most outstanding workers in the field of helminthology of marine mammals. PMID- 8474768 TI - [The distribution of Lernaea cyprinacea (Copepoda: Lernaeidae) in a crucian carp population]. AB - Differences in the infection with copepods and the character of distribution of occurrence frequencies of Lernaea in crucian carp depending on the body length and sex of the latter are shown. The lowest infection rate with copepods was recorded for fishes with body length 8-11 cm as compared to specimens with body length 12-18 and 18.5-34 cm. The two latter groups did not differ from each other in this index. In males and females whose body length is 8-11 cm as well as in females with body length 12-34 cm the occurrence frequencies of Lernaea are satisfactorily described by the negative binomial distribution curve. In males with body length 12-18 cm the occurrence frequencies of copepods are approximated by the binomial distribution curve. On the basis of obtained data it was concluded that fishes with a small body length as well as Carassius males and females with a greater body length represent three distinct host groups which differ in their part of maintaining the number of Lernaea of the host group. PMID- 8474769 TI - Diagnosis and treatment of discogenic low back pain. AB - Low back pain (LBP) is very prevalent in the general population. Treatment of nonradicular back pain, in the absence of deformity, continues to be controversial. Recently, anatomic dissections, magnetic resonance imaging studies, and the use of provocative discograms (pain-related response during the injection similar to the typical pattern of pain reported prior to the procedure) have contributed to our understanding of the etiology of discogenic back pain. Various techniques of spine fusion, with and without instrumentation, have altered the natural history of LBP unresponsive to conservative treatment. This review discusses the etiology and diagnosis of discogenic back pain and the treatment options available to the spine surgeon. PMID- 8474770 TI - Diagnostic imaging of childhood spinal infection. AB - Intervertebral disk space infection is common in children and has certain clinical and imaging characteristics. Until recently, the diagnosis has largely depended on plain roentgenography and/or radionuclide imaging. This article emphasizes the role of cross-sectional imaging, including computed tomography and magnetic resonance imaging in the evaluation of childhood spinal infections. PMID- 8474771 TI - The comprehensive diagnosis of spinal pain. A new psychodiagnostic instrument. AB - The psychological assessment of patients suffering back pain has become a standard part of comprehensive diagnostic protocol and an accepted responsibility of the clinical practitioner. This is for good reason, since research confirms the value of psychological evaluation to clinical diagnosis, treatment planning, and the outcomes of both medical and surgical treatment. However, the traditional psychological tests developed for use with psychiatric patients and in mental health settings are not appropriate for nonpsychiatric orthopaedic patients with back pain. However, a psychometric instrument has recently been developed for use with patients in pain. The Post-Traumatic Personality Profile (P-3) is a 48-item, multiple-choice, paper-and-pencil instrument that takes only 15 to 20 minutes. This article discusses the psychometric properties of the P-3 and presents a typical test interpretation. PMID- 8474772 TI - Ruptures of the proximal biceps tendon in middle-aged patients. AB - Treatment of ruptures of the proximal biceps tendon has been based on clinical observations, with little objective data to substantiate treatment guidelines. Evaluation of 25 patients (all > 40 years of age) at an average of 7.9 years after injury found few objective or subjective differences between those treated nonoperatively and those treated operatively. Only 1 patient (treated nonoperatively) was dissatisfied with the result, and her dissatisfaction was with a cosmetic defect. Objective manual muscle testing and Cybex II (Cybex Corporation, Ronkonkoma, New York) evaluation of 19 patients found no significant differences in supination or elbow flexion strength in the two groups. PMID- 8474773 TI - Ipsilateral fractures of the femoral neck and shaft. AB - The management of ipsilateral fractures of the femoral neck and shaft has proved to be a challenge to the orthopaedist. Most major institutions have treatment protocols that emphasize early rigid stabilization of the femoral-neck fracture to minimize the incidence of avascular necrosis of the femoral head. Since 1985, the authors' protocol has been to reduce and stabilize the femoral-neck fracture anatomically, followed by treatment of the femoral-shaft fracture. In 1990, we began treating this segmental fracture pattern with reconstruction nails. This study reviews the cases of 11 patients treated at the Medical College of Georgia Hospital from November 1985 to March 1992. Nine of the 11 underwent surgery within 12 hours of injury; 4 of these patients were treated with reconstruction nails. The mean follow-up was 2 years. Seven of the 11 had a good functional outcome, whereas 4 had a fair outcome. The results indicate that patients with ipsilateral fractures of the femoral neck and shaft can obtain good results when early (< 12 hours) rigid anatomic stabilization of the femoral neck is performed. The authors recommend utilizing a reconstruction nail for stabilizing this dual fracture whenever possible. PMID- 8474774 TI - Combined modality treatment for tumoral calcinosis. AB - Tumoral calcinosis is a rare syndrome marked by periarticular and intramuscular calcifications. We present the case of a 13-year-old black girl who has received treatment since age 2 for tumoral calcinosis with bilateral shoulder involvement. PMID- 8474775 TI - Osteochondritis dissecans of the knee in an adult with Stickler syndrome. AB - A 35-year-old man with hereditary progressive arthro-ophthalmopathy (Stickler syndrome) was treated for osteochondritis dissecans of the knee. As has been described in families with this autosomal-dominant connective-tissue disorder, phenotypic variation was present in his family; the patient's primary manifestations of the syndrome were ocular, but his brother had significant joint involvement. Osteochondritis dissecans of the knee may be a component of the arthrosis in this syndrome, but in the current case, the occurrence might have been coincidental. Stickler syndrome can be manifested by multiple musculoskeletal abnormalities, often early in life, and may be mistaken for several other diseases. PMID- 8474776 TI - Slipped disc. PMID- 8474777 TI - A 67-year-old woman with pain and tenderness in the left long finger. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenographic examinations are presented along with the final histologic and differential diagnoses. PMID- 8474778 TI - The use of staples in hand surgery. AB - Staples can be used in a variety of surgical procedures on the hand. They provide excellent retraction of skin flaps for which sutures would normally be placed, and their use often decreases the need for manual retraction. PMID- 8474779 TI - Fibular transport in conjunction with Hoffman external fixation of the tibia. AB - Tibiofibular synostosis is a salvage procedure commonly used for difficult nonunions of the tibia. It may be carried out by means of transfixion screws, a bone graft, or fibular transfer using Ilizarov (Smith and Nephews Richards, Memphis, Tennessee) or Monticelli-Spinelli (Howmedica Inc, Rutherford, New Jersey) devices. This paper describes fibular transfer employing the Hoffmann external fixator, which is commonly used in the management of tibial fractures or nonunions. PMID- 8474780 TI - Facilitating difficult catheter passage. AB - Passage of a flexible catheter into a septic flexor tendon sheath can be difficult and time consuming because of the catheter's pliability. This article discusses a technique for converting the flexible catheter into a semirigid stylet. PMID- 8474781 TI - Ontogeny of epithelial modulation of airway smooth muscle function in the guinea pig. AB - The purpose of this study was to investigate the ontogeny of guinea pig airway smooth muscle (ASM) responses and the epithelial modulation of these responses. Paired tracheal rings from fetal, newborn, and adult guinea pigs were studied. One of each pair was denuded of airway epithelium (AE) by gentle rubbing. Isometric tension was measured in rings mounted in organ baths filled with Krebs' solution. Cumulative dose-response curves were generated by adding either acetylcholine (ACh) or histamine over a concentration range of 10(-8)-10(-4) M. Significant agent-specific, age-related differences in maximal contraction were seen for both ACh and histamine in intact tissues (Ach: for fetus 66.7 +/- 6.2 x 10(-2) g/mg wet wt, for newborn 51.4 +/- 6.2, for adult 29.3 +/- 2.6; histamine: for fetus 46.1 +/- 5.1, for newborn 72.9 +/- 6.0, for adult 25.3 +/- 3.2). Similar differences in sensitivity to both agents were observed (EC50 with ACh: for fetus 0.80 +/- 0.11 x 10(-6) M; for newborn 0.85 +/- 0.26 x 10(-6) M; for adult 1.7 +/- 0.20 x 10(-6) M; EC50 with histamine; for fetus 1.88 +/- 0.50 x 10( 6) M; for newborn 1.34 +/- 0.16 x 10(-6) M; for adult 3.78 +/- 0.75 x 10(-6) M). Removal of AE caused a significant decrease in maximal responses to ACh in fetal tissue, a smaller, insignificant one for newborn and a nonsignificant alteration for adult tissues. Age-related sensitivity difference was abolished with removal of AE to ACh but not to histamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474782 TI - Nebulized steroid therapy in bronchopulmonary dysplasia. AB - The effect of inhaled beclomethasone dipropionate (BEC) was studied in seven infants between 7 and 18 months of age with glucocorticoid-dependent bronchopulmonary dysplasia. Oral glucocorticoid therapy, pulmonary function, growth, daily caloric consumption, blood pressure, blood sugar, blood gases, and immunoglobulins were monitored for 3 months before (control period) and 3 months after (intervention period) instituting inhaled beclomethasone dipropionate (25 micrograms/kg/day divided tid) delivered by Pulmoaide with a DeVilbiss nebulizer. Acute BEC inhalation produced no change in pulmonary function. During BEC treatment, oral glucocorticoid therapy was decreased in all infants, stopped in four infants within 3 months and in the other three infants in 4-5 months. Within 1 month of inhaled BEC the rate of linear growth and weight increased markedly (2.2 +/- 1.8 vs 6.4 +/- 2.4 cm/month - mean +/- SD and 9.3 +/- 6.5 vs 18.2 +/- 7.4 g/day, respectively without change in average daily caloric consumption (113 +/- 16 vs. 110 +/- 15 cal/kg/day). Immunoglobulins also significantly increased during BEC therapy (IgG(Total) 246 +/- 74 vs 463 +/- 111 mg/dL). Pulmonary function revealed moderate obstructive pulmonary disease before BEC. After 3 months of BEC inhalation no significant change occurred although respiratory system resistance decreased and the flow at 25% of tidal volume to peak flow ratio increased more than predicted by intersession variability. In no infant did pulmonary function decline after BEC, nor were any apparent adverse effects noted in this small group of patients. In conclusion, inhaled BEC was effective in decreasing oral glucocorticoid therapy and in modifying glucocorticoid-induced growth suppression in a very small, highly select group of infants with bronchopulmonary dysplasia. PMID- 8474783 TI - Evaluation of pulmonary functions during pressure-limited manual ventilation in preterm neonates. AB - Manual ventilation (MAV) or handbagging is a frequent and often life-saving procedure for neonates; however, few studies allow for an objective evaluation of techniques or possible risks. We compared parameters of ventilation and pulmonary mechanics obtained during routine pressure-limited MAV to those obtained during spontaneous breathing (SPB) in the same infant at approximately the same time. We selected 20 preterm neonates in the recovery phase of respiratory distress syndrome who received periodic MAV and were capable of optimum spontaneous minute ventilation (> 300 mL/kg/min). During MAV compared to SPB we measured higher tidal volume (8.1 +/- 0.5 SE vs. 5.4 +/- 0.4 SE mL/kg, P < 0.001), lower total pulmonary compliance (0.65 +/- 0.05 vs. 1.16 +/- 0.11 SE mL/cmH2O, P < 0.001), end-inspiratory compliance, higher pulmonary resistance (121 +/- 11 vs. 61 +/- 7 SE cmH2O/L/s, P < 0.001) and higher peak inspiratory airflow (2.8 +/- 0.2 vs. 1.6 +/- 0.1 L/s, P < 0.001). Inspiratory time (Ti) was consistently longer during MAV (0.49 +/- 0.02 vs. 0.36 +/- 0.02 SE, P < 0.001) such that during MAV the difference between actual Ti and minimal effective Ti (fivefold inspiratory time constant) was larger (0.29 +/- 0.03 vs. 0.13 +/- 0.03 s, P < 0.05). Our study suggests that operator-dependent ventilatory variables such as tidal volume, inspiratory time, frequency, and airflow need to be further evaluated in order to develop standardized guidelines for the safe administration of MAV. Until then the ventilator used for brief or augmented ventilatory support is a reasonable alternative to administering MAV by inconsistent standards. PMID- 8474784 TI - Late-onset miliary pneumonitis after near drowning. AB - We report a 7-year-old pediatric patient with an apparently self-limiting, subacute miliary pneumonitis that occurred 6 weeks after a near-drowning accident in shallow, muddy water. After biopsy, histological examination revealed aspirated foreign bodies (algae and pollen grains) in the affected lung areas and a foreign body reaction in the form of a granulomatous inflammation. The lack of any detectable infectious agents suggested a causative role of these aspirated algae and pollen grains in the development of lung disease. PMID- 8474785 TI - International consensus on the management of pediatric asthma: a summary statement. PMID- 8474786 TI - On exogenous surfactant therapy. PMID- 8474787 TI - Effects of air pollution on the respiratory tract of children. AB - The effects of air pollution on pulmonary function and respiratory status was evaluated in 1,626 school aged children from a European Alpine region. Based on measurements of SO2, NO2, and O3 as well as infrared imaging and lichen mapping, three zones of exposure were defined. Results of standardized respiratory questionnaires, medical examinations, and lung function tests were compared among the children in the three different exposure zones. After controlling for age, sex, height, socioeconomic status, and exposure to environmental tobacco smoking, areas of increased SO2 and NO2 as well as areas of increased ozone (max. half hourly mean value, 146 ppb) were significantly associated with decrements of forced expiratory volume in 1 s (FEV1) and flow rates at 50 and 75% of vital capacity (FEF50, FEF75). In addition, areas with increased ozone had a higher prevalence of asthma In all regions, maternal smoking was associated with reduced expiratory flow rates and increased prevalence of asthma. The results provide evidence that outdoor pollution and exposure to passive smoking are risk factors for childhood respiratory health. PMID- 8474788 TI - Pulmonary function between 6 and 18 years of age. AB - Pulmonary function of children aged 6-18 years is described based on 82,462 annual measurements of forced vital capacity (FVC), forced expired volume in 1 second (FEV1), and forced expiratory flow between 25% and 75% of FVC (FEF25-75%) from 11,630 white children and 989 black children. Median height, FVC, FEV1, FEV1/FVC, and FEF25-75% for each 3 months of age are compared among race and sex subgroups. Race- and sex-specific percentile distributions of FVC, FEV1, FEV1/FVC, and FEF25-75% are presented for each centimeter of height (growth curves). For the same height, boys have greater lung function values than girls, and whites have greater ones than blacks. Lung function increases linearly with age until the adolescent growth spurt at about age 10 years in girls and 12 in boys. The pulmonary function vs. height relationship shifts with age during adolescence. Thus, a single equation or the pulmonary function-height growth chart alone does not completely describe growth during the complex adolescent period. Nevertheless, race- and sex-specific growth curves of pulmonary function vs. height make it easy to display and evaluate repeated measures of pulmonary function for an individual child. Race-, sex-, and age-specific regression equations based on height are provided, which permit the evaluation of growth during adolescence with improved accuracy and, more importantly, in comparison with previous observations for the same child. PMID- 8474789 TI - The effect of age on bronchodilator responsiveness. AB - The relationship between age and bronchodilator responsiveness (BDR) in children has not been studied using objective parameters. The aim of this study was to seek such a relationship in young asthmatic children using dose-response curves (DRC). Fourteen asthmatic subjects (age 3-9 years) with a forced expiratory volume in 1 sec (FEV1) less than 80% predicted were studied after being trained to use a spirometer reliably. Each subject completed a DRC by inhaling 5 doses of salbutamol (albuterol) at 15 min intervals until a cumulative total of 6.84 mg of salbutamol had been administered. FEV1, forced vital capacity (FVC), and forced expiratory flow at mid vital capacity (FEF25-75) were measured before and after each nebulization. In addition, arterial oxygen saturation (SaO2) and heart rate (HR) were measured in some of the subjects. All lung function parameters, SaO2 and HR increased significantly between baseline and completion of the DRC. A significant age effect on BDR was detected in FEV1 and FVC, with older children showing a greater response than young ones. The response had plateaued after the maximum dose in the younger but not in the older children. These findings suggest that the level of response to a bronchodilator increases significantly with increasing age in young asthmatics. PMID- 8474790 TI - American Academy of Pediatrics Vitamin K Ad Hoc Task Force: Controversies concerning vitamin K and the newborn. PMID- 8474791 TI - American Academy of Pediatrics Committee on Early Childhood, Adoption, and Dependent Care: Developmental issues in foster care for children. PMID- 8474792 TI - American Academy of Pediatrics Committee on Substance Abuse: Role of the pediatrician in prevention and management of substance abuse. PMID- 8474793 TI - American Academy of Pediatrics Committee on Infectious Diseases: Vitamin A treatment of measles. PMID- 8474794 TI - Lactic acid and breast-feeding. PMID- 8474795 TI - Pediatric poisoning hazards. PMID- 8474796 TI - Sepsis and jaundice. PMID- 8474797 TI - Stewart smiled. PMID- 8474798 TI - Stewart smiled. PMID- 8474799 TI - Twins and HIV. PMID- 8474801 TI - A call for help. PMID- 8474800 TI - HIV and smooth muscle tumors. PMID- 8474802 TI - Acetaminophen hepatotoxicity after a prolonged ingestion. PMID- 8474803 TI - Cost-effectiveness of screening and cryotherapy for threshold retinopathy of prematurity. AB - BACKGROUND: Retinopathy of prematurity (ROP) is the leading cause of blindness among premature infants. A recent National Eye Institute-sponsored prospective, multicenter trial investigating the use of cryotherapy for treatment of ROP demonstrates a significant reduction in blindness and low vision for patients with sight-threatening (stage 3+) ROP. METHOD: A microsimulation model is presented to determine the cost-effectiveness of cryotherapy for ROP. Simulations are performed for three subpopulations of premature infants with birth weights 500 through 749 g, 750 through 999 g, and 1000 through 1249 g, and for three screening strategies--weekly, biweekly, and monthly. RESULTS: Appropriately timed screening for and treatment of ROP is predicted to result in a gain of 3899 to 4648 quality-adjusted-life-years and a net governmental budgetary savings of $38.3 to $64.9 million for each annual US birth cohort of 28,321 premature infants (500 through 1249 g). The cost per quality-adjusted-life-year gained is $2488 to $6045, depending on different screening strategies. CONCLUSIONS: Of greatest importance is the finding that properly timed screening and treatment for ROP is not only cost saving but may save approximately 320 infants per year from a lifetime of blindness. PMID- 8474804 TI - Exclusive breast-feeding for at least 4 months protects against otitis media. AB - OBJECTIVE: This study was designed to assess the relation of exclusive breast feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life. METHODS: Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables. RESULTS: Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered. CONCLUSION: These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media. PMID- 8474805 TI - Factors associated with condom use by sexually active male adolescents at risk for sexually transmitted disease. AB - OBJECTIVE: The purpose of this study was to identify the predictors of condom use in a population of male adolescents at risk for sexually transmitted diseases (STDs). DESIGN: Cross-sectional cohort study. SETTING: Clinical sites (school based, adolescent and STD clinics) providing reproductive health care to male adolescents in a midwestern city. PARTICIPANTS: One hundred sixteen male adolescents 15 to 19 years of age were enrolled consecutively. OUTCOME MEASURES: Subjects completed a multi-instrument questionnaire examining sexual behaviors, attitudes, and beliefs about STDs and condoms, cognitive maturity, and health risk behaviors; urethral specimens were cultured for Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: The median age was 17; 31% were white and 69% were African-American. Thirty-seven percent had urethral infections: 21% were infected with C trachomatis, 11% with N gonorrhoeae, and 5% with both organisms. More than 60% reported some experience with condoms and 23% reported condom use at last coitus. Consistent with the Health Belief Model, condom use for STD prevention was less likely among those reporting other health risk behaviors (odds ratio [OR] = 0.53; 95% confidence interval [CI] = 0.36 to 0.78; P < .001) and more STD risk behaviors (OR = 0.65; CI = 0.45 to 0.96; P = .03). Adolescents who were more highly motivated (OR = 1.58; CI = 1.09 to 2.30; P = .02) and who were more positive about condoms (OR = 1.83; CI = 1.25 to 2.68; P < .001) were more likely to report condom use for contraception. Adolescents using condoms for acquired immunodeficiency syndrome (AIDS) protection engaged in fewer behavioral (OR = .62; CI = 0.42 to 0.92; P = .02) and STD risks (OR = .67; CI = 0.45 to 0.99; P = .04). Three specific reasons for condom use were highly predictive of condom use at last intercourse: STD prevention (OR = 8.9; CI = 3.13 to 25.4; P < .001), birth control (OR = 2.1; CI = 1.05 to 4.25; P = .03), and AIDS prevention (OR = 2.4; CI = 1.05 to 5.42; P = .03). CONCLUSION: Condom use among adolescent males is influenced by perceived benefit, namely prevention of pregnancy & avoidance of STDs including AIDS. Nonuse is associated with other risk-taking behavior. PMID- 8474806 TI - Prevention of progression to severe obesity in a group of obese schoolchildren treated with family therapy. AB - STUDY OBJECTIVE: To evaluate the effect of family therapy on childhood obesity. DESIGN: Clinical trial. One year follow-up. SETTING: Referral from school after screening. PARTICIPANTS: Of 1774 children (aged 10 to 11), screened for obesity, 44 obese children were divided into two treatment groups. In an untreated control group of 50 obese children, screened in the same manner, body mass index (BMI) values were recorded twice, at 10 to 11 and at 14 years of age. INTERVENTION: Both treatment groups received comparable dietary counseling and medical checkups for a period of 14 to 18 months, while one of the groups also received family therapy. RESULTS: At the 1-year follow-up, when the children were 14 years of age, intention-to-treat analyses were made of the weight and height data for 39 of 44 children in the two treatment groups and for 48 of the 50 control children. The increase of BMI in the family therapy group was less than in the conventional treatment group at the end of treatment, and less than in the control group (P = .04 and P = .02, respectively). Moreover, mean BMI was significantly lower in the family therapy group than in the control group (P < .05), and the family therapy group also had fewer children with BMI > 30 than the control group (P = .02). The reduction of triceps, subscapular, and suprailiac skinfold thicknesses, expressed as percentages of the initial values, was significantly greater in the family therapy group than in the conventional treatment group (P = .03, P = .005 and P = .002, respectively), and their physical fitness was significantly better (P < .05). CONCLUSIONS: Family therapy seems to be effective in preventing progression to severe obesity during adolescence if the treatment starts at 10 to 11 years of age. PMID- 8474807 TI - Child day care, smoking by caregivers, and lower respiratory tract illness in the first 3 years of life. Group Health Medical Associates. AB - BACKGROUND: Day-care attendance has been associated with an increased risk of hospitalization for lower respiratory tract illnesses (LRIs). This study examines, in a health maintenance organization population of children, the associations between child day care and the occurrence of LRIs in the first 3 years of life. Smoking by caregivers and a possible protective effect of longer day-care enrollment in relation to LRIs are also addressed. METHODS: Information on day-care arrangements was elicited from 1006 parents of infants for five age intervals in the first 3 years of life: birth through 3 months, 4 to 6 months, 6 to 12 months, 1 to 2 years, and 2 to 3 years. Data on LRIs in the first 3 years of life were recorded by pediatricians at the time of the acute illnesses. RESULTS: After controlling for other risk factors, the presence of three or more unrelated children in the care setting was associated with significant risks of LRI of up to twofold or more from 4 months of age to 3 years. Type of care setting was not a significant risk factor during this time period. In the third year of life, the risk of wheezing LRI in the presence of a smoking caregiver was more than threefold for those in another residential home setting. No significant protective effect against LRIs in the third year of life associated with longer prior day-care enrollment was demonstrated. CONCLUSION: The presence of three or more unrelated children in the care setting and the presence of a smoking caregiver were significant independent risk factors for LRIs during the first 3 years of life. Prolonged day-care did not protect against LRIs in the third year of life. PMID- 8474808 TI - Smoking and the sudden infant death syndrome. AB - OBJECTIVE: Maternal smoking has been shown to be a risk factor for sudden infant death syndrome (SIDS). The effect of smoking by the father and other household members has not previously been examined. METHODS: A large nationwide case control study. Four hundred eighty-five SIDS deaths in the postneonatal age group were compared with 1800 control infants. RESULTS: Infants of mothers who smoked during pregnancy had a 4.09 (95% confidence interval [CI] = 3.28, 5.11) greater risk of death than infants of mothers who did not smoke. Infants of mothers who smoked postnatally also had an increased risk of SIDS compared with infants of nonsmokers and, furthermore, the risk increased with increasing levels of maternal smoking. Smoking by the father and other household members increased the risk (odds ratio [OR] = 2.41, 95% CI = 1.92, 3.02 and OR = 1.54, 95% CI = 1.20, 1.99, respectively). Smoking by the father increased the risk of SIDS if the mother smoked, but had no effect if she did not smoke. In analyses controlled for a wide range of potential confounders, smoking by the mother and father was still significantly associated with an increased risk of SIDS. CONCLUSION: Passive tobacco smoking is causally related to SIDS. PMID- 8474809 TI - Increases in crash involvement and fatalities among motor vehicle occupants younger than 5 years old. AB - OBJECTIVE: To determine whether increased exposure as car occupants could be a major contributor to increases observed in deaths of young children in car crashes. DESIGN AND SETTING: Crash data from police reports for Maryland, Michigan, Pennsylvania, and Washington for various years from 1982 through 1990 were examined to compare annual age mix of injured and uninjured occupants in crashes involving at least two passenger vehicles. Aggregate national data from the Fatal Accident Reporting System were also examined over the same time period and compared to population estimates for children younger than 5 years old to assess temporal trends in number of occupants in this age group who were involved in motor vehicle crashes in which a fatality occurred in fatal crashes and the number of them killed in passenger vehicles. RESULTS: In regression analyses for each state, the number of car occupants younger than 5 involved in crashes increased during the years studied; their percentage among nondriver occupants involved also increased. At a national level, similar analyses showed increases in the number of occupants younger than 5 involved in crashes in which a fatality occurred. CONCLUSIONS: Despite overall increases in the use of restraint devices (ie, both child safety seats and adult restraints), fatalities among restrained children have increased. Given that exposures to crash environments are increasing, clinicians need be aware of the importance of child restraints as a means of reducing the likelihood of injury. PMID- 8474810 TI - Cost-effectiveness analysis of bicycle helmet subsidies in a defined population. AB - OBJECTIVE: To examine the potential effects of bicycle safety helmet cost subsidy on bicycle head injury rates and costs. DESIGN: Using empiric data on the incidence and costs of bicycle injuries to children, we examined the hypothetical effects of various bicycle helmet subsidies in a cost-effectiveness analysis. A hypothetical cohort of 100,000 5- through 9-year-olds was followed for 5 years after helmet cost subsidization. Sensitivity analyses were done of three different levels of safety helmet subsidy ($5, $10, $15), three discount rates (2%, 4%, 6%), 10 levels of safety helmet use ranging from 10% to 100%, and the occurrence or nonoccurrence of catastrophic head injuries. PATIENTS: Forty-three children 5 through 9 years of age and 27 children 10 through 14 years of age with head injuries due to bicycling were identified through emergency department surveillance of a population of 29,533. SETTING: Group Health Cooperative of Puget Sound, a large health maintenance organization. OUTCOME MEASURES: Bicycle head injuries prevented and the savings or costs associated with various subsidy, safety helmet use, and discount rates. RESULTS: Hypothetically, an increase in bicycle helmet use rates to 40% to 50% due to subsidies of $5 or $10 prevents 564 to 840 head injuries in a cohort of 100,000 5- through 9-year-olds over 5 years. Under these conditions and a 2% discount rate, cost savings ranging from $189,207 to $427,808 will result when catastrophic head injuries are included in the analysis. CONCLUSION: Subsidization of bicycle safety helmets to achieve a cost of $14 to $20 per helmet and use rates of 40% to 50% will likely prove cost effective. Empirical evidence from a Seattle campaign suggests that such helmet use rates are achievable. PMID- 8474811 TI - Evaluation of two iron-fortified, milk-based formulas during infancy. AB - OBJECTIVE: Compare milk-based, iron-fortified formulas containing 7.4 and 12.7 mg/L iron and breast-feeding during the first year of life. DESIGN: Partially randomized, double-blind trial: non-breast-fed infants randomly assigned to receive one of two coded formulas, identical except for iron content; infants discontinuing breast-feeding between 1 and 8 weeks of age randomly assigned to a formula late-start group. SETTING: Five general community pediatric practices in Missouri, Indiana, Illinois, and Pennsylvania. PARTICIPANTS: Sample of 347 healthy, term infants, enrolled within 1 week after birth; 172 included in statistical analyses. OUTCOME MEASURES: Length, weight, and indicators of formula intolerance recorded at clinic visits; formula consumption, bowel movements, stool consistency, and other tolerance indicators recorded by parents on daily and weekly report forms; hemoglobin, hematocrit, and serum ferritin, iron zinc, and copper measured at 6 and 12 months. RESULTS: No significant differences between formula-fed groups in growth, attrition, formula consumption, bowel movements, hematocrit, hemoglobin level, and serum iron, zinc, and copper levels (P > .05); first 6-month weight and length changes of the breast-fed group significantly less than in both formula-fed groups (P < .008); serum ferritin level of the formula-fed, high-iron group significantly higher than that of the low-iron and breast-fed groups (P < .008), although all groups' values were normal; no apparent differences between formula groups in formula tolerance and stool characteristics but data were not analyzed statistically. CONCLUSIONS: Milk based formulas containing either 7.4 or 12.7 mg/L iron support normal growth and iron status of healthy, term, normally fed infants during the first year and both are well tolerated and accepted. PMID- 8474812 TI - New postnatal growth grids for very low birth weight infants. AB - OBJECTIVE: To generate contemporary postnatal growth curves for hospitalized very low birth weight infants. DESIGN: Retrospective survey. SETTING: Tertiary intensive care nursery. PATIENTS: All surviving singleton, appropriate-for gestational age infants with birth weight < or = 1500 g, born January 1, 1987, to May 31, 1991, who did not develop necrotizing enterocolitis (N = 205). MEASUREMENTS AND RESULTS: Macronutrient intakes and body weights were recorded daily, with crown-heel length and occipital-frontal head circumference recorded weekly up to 105 days of age or hospital discharge, whichever occurred first. Growth curves were generated for four birth weight ranges: 501 through 750, 751 through 1000, 1001 through 1250, and 1251 through 1500 g. Compared to previously published growth curves, the current infants regained birth weight more quickly and exhibited larger average daily weight gains. These differences were most apparent in infants of lowest birth weight. CONCLUSIONS: The "premature growth grid" constructed by Dancis et al more than 40 years ago may no longer be a useful standard of early postnatal growth for present-day very low birth weight, appropriate-for-gestational-age infants. The new weight curves are a more accurate reflection of current in-hospital growth trends, especially for infants weighing < or = 1000 g at birth. PMID- 8474813 TI - Families on the move and children's health care. AB - OBJECTIVE: To evaluate the relationship of family moves to children's health care use. DESIGN: Analyses of data from the 1988 National Health Interview Survey of Child Health (NHIS-CH). This survey uses a multisite probability cluster technique to achieve nationally representative estimates of health and demographic characteristics of the US civilian population. PARTICIPANTS: 17,110 US children and their families who took part in the 1988 NHIS-CH. MEASUREMENTS: The 1988 NHIS-CH collected health and demographic data including family mobility information on 17,110 US children and their families. This study analyzed the relationship of number of family moves to reporting a regular site for preventive pediatric health care services, a regular site for pediatric sick care, and routine use of emergency departments when a child was sick. RESULTS: Overall, 8% of US children were reported to lack a regular site for preventive care services, 7% a site for sick care, and 3% routinely used an emergency department for sick care. However, 14% of children who had moved three or more times lacked a regular site for preventive care and 10% lacked a regular site for sick care, compared to only 3% of children who had never moved. Children who had moved more than twice were three times as likely to lack a regular site for preventive or sick care and 1.6 times as likely to use an emergency department for sick care, as were children who had never moved. CONCLUSIONS: Families with increased mobility are more likely to lack a regular site for both preventive and sick care and to use emergency departments when their children become ill. PMID- 8474814 TI - Risk factors and outcomes for failure to thrive in low birth weight preterm infants. AB - OBJECTIVE: To determine the epidemiology, clinical characteristics, and outcomes for low birth weight (LBW) infants with growth deficiency, or failure to thrive (FTT, the term commonly used by pediatric providers to describe growth deficiency or faltering in early childhood). DESIGN: Three-year prospective cohort study with matched case-control study of outcomes. SETTING: Eight large university hospital sites throughout the United States. SAMPLE: 914 LBW infants inborn at the sites and meeting study criteria. RESULTS: FTT was a common condition in this cohort, with 180 (19.7%) of 914 LBW infants meeting case criteria by 30 months. New cases of FTT peaked at 8 months gestation-corrected age. In addition to expected differences in growth between infants with and without FTT, infants with FTT had lower developmental indices and less stimulating home environments. At 36 months, FTT infants had lower IQ scores and were much smaller than infants without FTT. CONCLUSIONS: Growth deficiency, or FTT, is a common clinical condition for those involved in the follow-up care of LBW infants. Worse cognitive and growth outcomes were observed for those meeting the restrictive case criteria employed in this study. More than 80% of the cases in this LBW cohort did not involve any chronic medical disorders, but several biological and environmental differences were found between those who developed FTT and those who did not. PMID- 8474815 TI - Tracking of serum cholesterol and lipoprotein levels from the first year of life. AB - OBJECTIVE: To examine the development of tracking of serum cholesterol concentration from birth to childhood. DESIGN: In a longitudinal study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193); at 2 (n = 192), 4 (n = 192), 6 (n = 190), 7.5 (n = 118), 9 (n = 188), and 12 months (n = 196); and at 5 years of age (n = 162). Concentrations of cholesterol--very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein-2 (HDL2), and HDL3--were determined at 2, 6, 9, and 12 months (n = 36) and at 5 years (n = 162). RESULTS: The correlation coefficients of total cholesterol levels during the first year of life with the level at 5 years of age were as follows: at birth .04, at 2 months .36 (P < .001), at 4 months .26 (P < .001), at 6 months .28 (P < .001), at 7.5 months .25 (P < .001), at 9 months .35 (P < .001), and at 12 months .48 (P < .001). The correlation for exclusively breast-fed children between 6 months and 5 years of age was r = .37, P < .001, while that for children receiving partially breast milk, formula, or solid foods was r = .12, P = not significant (NS), and between 9 months and 5 years r = .38, P < .01, and r = .28, P < .05, respectively. The correlation coefficients of the lipoprotein levels between ages 12 months and 5 years were as follows: low-density lipoprotein cholesterol .58 (P < .001), total HDL cholesterol .30 (P < .05), HDL2 cholesterol .34 (P < .05), HDL3 cholesterol .17 (P = NS), very-low-density lipoprotein cholesterol .24 (P = NS), total triglyceride .37 (P < .05), and triglyceride-very-low-density lipoprotein .37 (P < .05). Of the children whose total serum cholesterol level was above the 90th percentile at birth, or at 2, 4, 6, 7.5, 9, or 12 months, 6%, 35%, 29%, 30%, 31%, 33%, and 45%, respectively, were above the 90th percentile at 5 years of age. In retrospect, 45% of the children whose serum cholesterol level was above the 90th percentile at 5 years were above the 90th percentile at the age of 12 months and 80% were in the highest quartile. CONCLUSIONS: The results indicate that tracking of serum cholesterol concentration during the first year of life is stronger when examining children who are receiving a relatively homogenous diet, such as exclusive breast-feeding, and weaker as children are weaned to formula and solid foods. After the weaning process is completed, children's relative serum cholesterol levels have become established and the tracking of serum cholesterol is of the same magnitude as for older children and adolescents. PMID- 8474816 TI - Dietary approaches for reducing fat intake of preschool-age children. AB - STUDY OBJECTIVE: The present study was conducted to determine the effects of applying different fat reduction strategies to the overall nutrient profile of diets for preschool-age children. DESIGN: Computer modeling techniques were used to modify the diets of children (ages 2 through 3 and 4 through 5 years old) to meet contemporary dietary recommendations (< 30% of calories from total fat, < 10% from saturated fatty acids, and < 300 mg of cholesterol daily). Fat reduction strategies were applied to a 1-week menu that included preschoolers' favorite foods. Strategies applied were replacing high-fat meat exchanges with lean meat exchanges (+/- three high-fat meat exchanges per week), replacing higher fat milks with skim milk, replacing high-fat meat exchanges with medium-fat meat exchanges, using fat-modified products, using low-fat preparation techniques, and added fat. All diets were made isocaloric after modifications were applied. RESULTS: It is more difficult to meet all recommendations for the 2- and 3-year old children. Use of skim milk is the simplest strategy to use for the 4- and 5 year-old children, although other single strategies are effective. CONCLUSIONS: When multiple strategies are effected. Some diets are very low in fat (< 20% of calories) and potentially inadequate in energy and nutrients. It is important that caregivers know the appropriate foods to choose when modifying fat in children's diets to ensure meeting energy and nutrient requirements. PMID- 8474817 TI - Infants of less than 1250 grams birth weight at Groote Schuur Hospital: outcome at 1 and 2 years of age. AB - A prospective 2-year follow-up study of infants with birth weights of less than 1250 g was undertaken at Groote Schuur Hospital Neonatal Intensive Care Unit. For a 12-month period beginning July 1988, all live infants born at Groote Schuur Hospital or referred to the Neonatal Intensive Care Unit were included in the study cohort. The aim of the study was to document the morbidity, mortality, and neurodevelopmental outcome of these infants to 2 years of age. Of 235 liveborn infants, 143 (61%) survived to discharge. One hundred twenty-six infants were born weighing less than 1000 g; 42% survived to discharge. One hundred nine infants weighed 1000 g or more at birth, and 83% survived to discharge. Better survival was documented for infants whose mothers attended antenatal care, who weighed more than 900 g, and who were of greater than 30 weeks' gestation. Eleven infants died in the first 6 months after discharge. One hundred six infants (83% of survivors) underwent Griffiths developmental testing and clinical assessment at 1 year of age. Ninety-six (91%) of these survivors were seen and tested at 2 years of age. Of the 106 infants assessed at 1 year of age, 6 infants had cerebral palsy, 6 were globally developmentally delayed without signs of cerebral palsy, and 1 infant showed significant motor delay with a normal developmental quotient. At 2 years of age 1 additional infant had cerebral palsy and 9 more infants are likely to be mentally retarded. At 2 years of age the major handicap rate was, therefore, 22%. Sixty-nine percent of surviving infants, and all but 1 of the infants with cerebral palsy, were underweight for gestational age at birth. There was a tendency for these underweight-for-gestational-age infants to score less well at 2 years of age. Infants who received ventilation and infants with a birth weight of less than 1000 g were not found to score less well than other infants in the cohort. PMID- 8474818 TI - Birth weight and illness severity: independent predictors of neonatal mortality. AB - BACKGROUND: Low birth weight is a major determinant of neonatal mortality. Yet birth weight, even in conjunction with other demographic markers, is inadequate to explain the large variations in neonatal mortality between intensive care units. This variation probably reflects differences in admission severity. The authors have recently developed the Score for Neonatal Acute Physiology (SNAP), an illness severity index specific for neonatal intensive care, and demonstrated illness severity to be a major determinant of neonatal mortality. OBJECTIVE: To define the relative contributions of birth weight and illness severity to the risk of neonatal mortality and to identify other significant independent risk factors. METHODS: Logistic regression was used to analyze data from a cohort of 1621 consecutive admissions to three neonatal intensive care units (92 deaths), to test six alternative predictive models. The best logistic model was then used to develop a simple additive clinical score, the SNAP Perinatal Extension (SNAP PE). RESULTS: These analyses demonstrated that birth weight and illness severity are powerful independent predictors across a broad range of birth weights and that their effects are additive. Below 750 g, there is an interaction between birth weight and SNAP. Other factors that showed independent predictive power were low Apgar score at 5 minutes and small size for gestational age. Separate derivation and test samples were used to demonstrate that the SNAP-PE is comparable to the best logistic model and has a sensitivity and specificity superior to either birth weight or SNAP alone (receiver-operator characteristic area .92 +/- .02) as well as excellent goodness of fit. CONCLUSION: This simplified clinical score provides accurate mortality risk estimates for application in a broad array of clinical and research settings. PMID- 8474819 TI - Effectiveness of iron-fortified infant cereal in prevention of iron deficiency anemia. AB - BACKGROUND: Iron deficiency continues to be a common problem among infants throughout the world. Iron-fortified formula is effective in preventing iron deficiency but the benefit of iron-fortified cereal is controversial. METHODS: We compared iron-fortified rice cereal to unfortified rice cereal in infants who were exclusively breast-fed for more than 4 months and to iron-fortified formula in infants who were weaned to formula before 4 months of age. The design was double blind in respect to the presence or absence of fortification iron in the cereal or formula and included 515 infants who were followed on the protocol from 4 to 15 months of age. Rice cereal was fortified with 55 mg of electrolytic iron per 100 g of dry cereal and infant formula with 12 mg of ferrous sulfate per 100 g of dry powder, levels approximating those in use in the United States. Measures of iron status were obtained at 8, 12, and 15 months. Infants with hemoglobin levels of < 105 g/L were excluded from the study and treated. RESULTS: Consumption of cereal reached plateaus at means of about 30 g/d after 6 months of age in the formula-fed groups and 26 g/d after 8 months in the breast-fed groups; these amounts are higher than the 19-g/d mean intake by the 73% of infants who consume such cereal in the United States. Among infants weaned to formula before 4 months, the cumulative percentages of infants excluded for anemia by 15 months were 8%, 24%, and 4%, respectively, in the fortified cereal, unfortified cereal and formula, and fortified formula groups (P < .01 unfortified vs either fortified group; the difference between the two fortified groups was not significant). In infants breast-fed for more than 4 months, the corresponding values were 13% and 27%, respectively, in the fortified and unfortified cereal groups (P < .05). Mean hemoglobin level and other iron status measures were in accord with these findings. CONCLUSION: Iron-fortified infant rice cereal can contribute substantially to preventing iron deficiency anemia. PMID- 8474820 TI - Intraoperative anaphylaxis to latex. PMID- 8474821 TI - Screening urine of 3-week-old newborns: lack of association between sudden infant death syndrome and some metabolic disorders. PMID- 8474822 TI - Leber's hereditary optic neuropathy as a cause of severe visual loss in childhood. PMID- 8474823 TI - Spectrum of limb disruption defects associated with chorionic villus sampling. PMID- 8474824 TI - A simplified behavioral treatment for trichotillomania: report of two cases. PMID- 8474825 TI - Arginase deficiency presenting as cerebral palsy. PMID- 8474826 TI - Inhalational nitric oxide therapy for persistent pulmonary hypertension of the newborn. PMID- 8474827 TI - Diagnosing and treating health: bright futures. PMID- 8474828 TI - Multiple reflections. PMID- 8474829 TI - A comparison of self-adaptation and cross-adaptation to odorants presented singly and in mixtures. AB - Fifteen subjects made 450 judgments each by the method of magnitude estimation of dimethyl disulfide and hydrogen sulfide after prior exposure to various mixtures of them. Exposure to the same odorant clearly affected the perceived intensity of it (self-adaptation). By contrast, exposure to the other odorant showed at best a small effect (cross-adaptation). Consistent with this, adaptation to a mixture of the test odorant and another odorant is proportional to the amount of the test odorant in the mixture, and does not exceed that of self-adaptation. These results indicate that olfactory adaptation is specific and that the sense of smell is more robust than generally assumed. PMID- 8474830 TI - Accuracy and consistency of absolute pitch. AB - The accuracy and consistency of absolute pitch (AP) judgments have been measured on three subjects in two longitudinal studies separated by twenty years. The drifts and cyclical variations observed in the earlier study still persisted, and an investigation of two other subjects, one of whom was first studied forty years ago, suggests that they might undergo similar cyclical variations in their pitch perception. Pitch judgments also varied during the day. The detailed observations of these nonrandom fluctuations have been used to determine a value for the underlying consistency of the AP estimates. When the effects of the daytime variations and longer-term drifts were removed, the values for this consistency, as measured by the standard deviation, were calculated to be 3.1, 3.4, 3.7, 4.4, and 4.5 Hz for the five subjects. When an oscillator was used to produce the estimate, the consistency of the judgments was observed to depend on the accuracy of those judgments. PMID- 8474831 TI - Action categories and the perception of biological motion. AB - Johansson filmed walkers and runners in a dark room with lights attached to their main joints and demonstrated that such moving light spots were perceived as human movements. To extend this finding the detection and recognition of Johansson displays of different kinds of movements under three light-spot conditions were studied to determine how human actions are perceived on the basis of biological motion information. Locomotory, instrumental, and social actions were presented in each condition, namely in normal Johansson (light attached to joints), inter joint (light attached between joints), and upside-down Johansson. Subjects' verbal responses and recognition times were measured. Locomotory actions were recognised better and faster than social and instrumental actions. Furthermore, biological motions were recognised much better and faster when the light-spot displays were presented in the normal orientation rather than upside down. Recognition rate was only slightly impaired under the inter-joint condition. It is argued that the perceptual analysis of actions and movements starts primarily on an intermediate level of action coding and comprises more than just the similarity of movement patterns or simple structures. Additionally, coding of dynamic phase relations and semantic coding take place at very early stages of the processing of biological motion. Implications of these results for computer vision, perceptual models, and mental representations are discussed. PMID- 8474832 TI - Perceived rigidity and nonrigidity in the kinetic depth effect. AB - Stroboscopic simulations of three-dimensional rotating rigid structures can be perceived as highly nonrigid. To investigate this nonrigidity effect a sequence of either three (experiment 2 and 3) or thirty six frames (experiment 4) was used, each consisting of a set of dots with location on the horizontal axis corresponding to the parallel projection of a nominally defined helix. Observers were asked to judge the angle of rotation of eighty helices defined by the factorial combination of eight phase (phi) values (ie difference between the sinusoidal path of one dot and its neighbours) and ten different angular displacement values (alpha). When in each static frame the dots can be organized into curved dotted line (small values of phi), the perceived 3-D helices are highly nonrigid. But when shape information is not available in each static frame (high values of phi), the helices are perceived as rigid and rotation judgement is possible providing that alpha < 15 degrees. It appears that at small values of phi observers fail to recover the rigid structure of the helices since the input to the structure from the motion process may be distorted. PMID- 8474833 TI - Comparison of nine methods of indicating the direction to objects: data from blind adults. AB - Nine methods of indicating the direction to object locations were tested on twenty blind adult subjects. The task was to indicate the location of active auditory targets distributed in a semicircle with a 1.7 m radius around the subject. Target location, practice, and feedback were systematically varied for each method. The greatest accuracy and lowest variability were found for pointing methods that used body parts (directing the nose at the target, facing it with the chest, and pointing with the index finger) and extensions of body parts (pointing with a hand-held cane or with a short stick). Two less accurate methods involved rotating a dial. The least accurate methods involved drawing and a verbal description in terms of clockface labels. Method interacted significantly with target location, and with individual differences. In general, the body-part and extension method were affected less than other methods by target location and individual differences. The findings suggest that a pointing response that uses body part or an extension of a body part is the best choice for experimental or diagnostic measurement of object location by blind subjects. Differences between the results of this study of blind subjects and auditory localization accuracy in sighted subjects are discussed, and the implications for spatial processing in the blind are considered. PMID- 8474834 TI - The effect of linear vection on manual aiming at memorized directions of stationary targets. AB - Stationary observers were required to aim manually at either a straight-ahead, or a lateral, immobile target (0 degrees and 20 degrees of eccentricity, respectively). First, they aimed at a perceptually present target. Second, they aimed at the memorized direction of the target. Third, they aimed at the memorized direction of the target after a 4 s period of forward sagittal vection. The comparisons of the post-vection versus ante-vection aimings at the memorized direction of the targets reflect an illusory increase in the eccentricity of the lateral target, and no change in the direction of the straight-ahead target. These results objectivate the idea that forward sagittal vection (a particular case of linear vection) corresponds to an illusion of self-displacement, ie an illusory change of body place through space. PMID- 8474835 TI - Is a perceived shape based on its retinal image? AB - Although the processing of phenomenal shape might be supposed to begin at an early stage, with the shape of the retinal image of an object, it is possible that it does not begin until a later stage at which the locations of the parts of the object have been perceived. Such perceived locations are based on a compensation or constancy mechanism that takes account of eye position. Ordinarily these two possible bases of shape perception--retinal image and perceived location--are confounded. To separate them the parts of a shape were presented sequentially, during which time the eyes were in motion. The eye movement did not alter phenomenal locations of the parts vis-a-vis one another but did yield an entirely different composite retinal image of the parts. Another method employed was to change the location of each sequentially presented part with respect to a displacing frame of reference. By and large the results indicate that the composite shape perceived is based on the perceived location of the parts of the object with respect to one another, rather than on the composite retinal image. PMID- 8474836 TI - The Pulfrich pendulum phenomenon in stereoblind subjects. AB - The Pulfrich pendulum phenomenon, in which a pendulum swinging in the frontoparallel plane appears to swing in an ellipse when a neutral density filter is placed over one eye of the observer, was investigated in stereoblind subjects. It was found that such subjects can report the presence of the Pulfrich effect although they fail to fuse random-dot stereograms and fail to exhibit interocular transfer of the movement aftereffect. These findings suggest that 'stereoblind' subjects must retain some residual binocular mechanism for depth perception. Three possibilities are considered: (i) the stereoblind may be able to utilise contiguous temporal disparities as a cue for depth in the Pulfrich effect; (ii) they may retain some residual binocularity, sufficient to reveal the Pulfrich effect but not for other more demanding tasks for the binocular mechanisms; and (iii) they may retain some coarse magnocellular pathway disparity mechanism having lost their high-acuity parvocellular disparity system. There is little evidence to support any of these hypotheses, but the third shows promise. PMID- 8474837 TI - Visual recognition in the peripheral field: letters versus symbols and adults versus children. AB - The plot of the form-resolving field (FRF) was obtained by tachistoscopically presenting two figures in each stimulus, one in the center of gaze and the other in the peripheral field. The figures in the periphery were placed at various eccentricities in different presentations. The ensuing plot of average letter recognition as a function of eccentricity is the FRF. Only the horizontal components of the FRFs were used in the comparisons. Three sets of figures were used as stimuli: regular-size letters, large-size letters, and symbols. Three groups of subjects were compared: adult ordinary readers, reading children, and pre-reading-age children. The last were tested with symbols only. In letter recognition, the FRFs for young and adult ordinary readers are similar and fall off monotonically and symmetrically with eccentricity, hence conforming with the first Aubert-Foerster law (1857). However, the FRFs tested with symbols are narrower than those tested with letters of the same sizes and stroke widths, which is not in accordance with the first Aubert-Foerster law. In addition, the FRFs of symbols are different for each subject group. It is suggested that recognition in the peripheral field is not determined by visual acuity alone; rather, it is further confined or determined by the visual strategy employed to accomplish the task, and its associated distribution of lateral masking. PMID- 8474838 TI - Time estimation methods--do they influence prospective duration estimates? AB - The validity of an attentional model of prospective time estimation was tested in three experiments. In the first experiment two variables were manipulated: (1) nontemporal information processing load during the estimated interval, and (2) time estimation method, ie production of time simultaneously with the performance of a second task, or reproduction of time immediately upon termination of a task whose duration has to be measured. As predicted, a positive relationship between produced time length and information processing load demanded by a simultaneous task, and a negative relationship between reproduced time length and information processing load during the estimated interval, were found. The results were replicated in a second experiment in which verbal estimates of time were also measured and the objective duration of the estimated interval was varied. The pattern of results obtained for verbal estimates was similar to that obtained for reproduced ones. The results of a third experiment indicated that produced and reproduced times were positively correlated with clock time. The results are interpreted as supporting an attentional model of prospective time estimation. PMID- 8474839 TI - Rocking the role of universities. PMID- 8474840 TI - Sex discrimination: how do we tell the difference between male and female faces? AB - People are remarkably accurate (approaching ceiling) at deciding whether faces are male or female, even when cues from hair style, makeup, and facial hair are minimised. Experiments designed to explore the perceptual basis of our ability to categorise the sex of faces are reported. Subjects were considerably less accurate when asked to judge the sex of three-dimensional (3-D) representations of faces obtained by laser-scanning, compared with a condition where photographs were taken with hair concealed and eyes closed. This suggests that cues from features such as eyebrows, and skin texture, play an important role in decision making. Performance with the laser-scanned heads remained quite high with 3/4 view faces, where the 3-D shape of the face should be easiest to see, suggesting that the 3-D structure of the face is a further source of information contributing to the classification of its sex. Performance at judging the sex from photographs (with hair concealed) was disrupted if the photographs were inverted, which implies that the superficial cues contributing to the decision are not processed in a purely 'local' way. Performance was also disrupted if the faces were shown in photographic negatives, which is consistent with the use of 3 D information, since negation probably operates by disrupting the computation of shape from shading. In 3-D, the 'average' male face differs from the 'average' female face by having a more protuberant nose/brow and more prominent chin/jaw. The effects of manipulating the shapes of the noses and chins of the laser scanned heads were assessed and significant effects of such manipulations on the apparent masculinity or femininity of the heads were revealed. It appears that our ability to make this most basic of facial categorisations may be multiply determined by a combination of 2-D, 3-D, and textural cues and their interrelationships. PMID- 8474841 TI - What's the difference between men and women? Evidence from facial measurement. AB - Human subjects are able to identify the sex of faces with very high accuracy. Using photographs of adults in which hair was concealed by a swimming cap, subjects performed with 96% accuracy. Previous work has identified a number of dimensions on which the faces of men and women differ. An attempt to combine these dimensions into a single function to classify male and female faces reliably is described. Photographs were taken of 91 male and 88 female faces in full face and profile. These were measured in several ways: (i) simple distances between key points in the pictures; (ii) ratios and angles formed between key points in the pictures; (iii) three-dimensional (3-D) distances derived by combination of full-face and profile photographs. Discriminant function analysis showed that the best discriminators were derived from simple distance measurements in the full face (85% accuracy with 12 variables) and 3-D distances (85% accuracy with 6 variables). Combining measures taken from the picture plane with those derived in 3-D produced a discriminator approaching human performance (94% accuracy with 16 variables). Performance of the discriminant function was compared with that of human perceivers and found to be correlated, but far from perfectly. The difficulty of deriving a reliable function to distinguish between the sexes is discussed with reference to the development of automatic face processing programs in machine vision. It is argued that such systems will need to incorporate an understanding of the stimuli if they are to be effective. PMID- 8474842 TI - Visual size invariance does not apply to geometric angle and speed of rotation. AB - The ability of humans to visually estimate geometric angle and speed of rotation was examined as a function of the spatial scale of the stimuli. Both properties are objectively invariant at different spatial scales, but the results of experiments show that the judgement of acute geometric angles as well as that of speed of rotation varies strongly and monotonically with the scale of presentation. If the image is magnified, the perceived geometric angle and the perceived speed of rotation increase. If the image is reduced in size, they decrease. This result imposes strong constraints on perceptual theories. PMID- 8474843 TI - A general correspondence approach to apparent motion. AB - A general framework is considered for how different features of image parts determine the perceived direction of apparent motion between these parts as a function of their internalized feature weights. It is shown how the compatibility and constraints between pairwise part correspondences also play important roles in the types of perceived motion between parts; this process is modelled via a multivariate constraint-satisfaction procedure. PMID- 8474844 TI - Directional bias in the perception of translating patterns. AB - Recent findings suggest that the visual system is biased by its past stimulation to detect one direction of motion over others. Three experiments were designed to investigate whether this bias is mediated by the direction or by the velocity of the past stimulation, and whether this bias is offset by contradictory pattern or depth information. Observers were presented with two solid or random-dot patterns that moved across a display screen in antiphase. As the two patterns reached the center of the screen, they became superimposed in such a way that their subsequent directions were ambiguous. Results from experiment 1 showed that the probability of perceiving these patterns as continuing to move in the same directions was significantly greater when they moved at a constant velocity than when they moved at a variable velocity. Results from experiments 2 and 3 revealed that this directional bias was reversed only gradually as an increasing amount of contradictory pattern information was introduced, but that this reversal was quite abrupt when a relatively small amount of contradictory depth information was introduced. Collectively, these results suggest that a directional bias in the perception of moving patterns is mediated not only by the direction of the previous stimulation, but also by the velocity of that stimulation. Moreover, the analyses of pattern and motion information appear relatively independent during the early stages of visual processing, but the analyses of depth and motion information appear considerably more interdependent. PMID- 8474845 TI - The perception of 3-D rotation from translating sine-wave lines: the reverse of the barber-pole illusion. AB - An ambiguous moving pattern which gives rise to the reverse of the barber-pole illusion is reported. When vertical sine-wave lines translate, vertically and endlessly, on a two-dimensional (2-D) plane, one can perceive rotating three dimensional (3-D) helixes without the impression of translation. With a single sine-wave line, 3-D rotation was seen for about half the exposure period. With three sine-wave lines shifted in phase by 120 degrees, this illusion easily arose when one fixated a point near the endpoints of the lines, which moved horizontally and sinusoidally along the imaginary upper edge of the screen. When 3-D rotation was seen, the sine-wave lines which were intersecting on a 2-D display were perceptually decomposed into pairs of lines separated in depth. On fixating a point at the center of the figure, vertical translation was mainly seen. Foveal viewing of the horizontal sine movement of the endpoints of the lines produces the impression of 3-D rotation and the impression appears to provide some specific information towards solving the aperture problem and towards reconstructing the whole figure as such. PMID- 8474846 TI - The role of depth stratification in the solution of the aperture problem. AB - When a plaid pattern composed of a stationary vertical grating and a horizontally drifting diagonal grating is shown behind a circular aperture, the pattern appears to move coherently in a vertical direction. When the bars of the stationary grating are narrower than those of the moving grating, only the latter is seen to move, in a direction orthogonal to its orientation (ie diagonal); but when the bars of the stationary grating are wider than those of the moving grating, vertical motion of the whole plaid predominates. It is argued that, in the absence of occlusion information, the motion of a plaid within an aperture depends on the unambiguous displacement of inner line terminators at the crossings of the two gratings. Relative motion and differences in bar width between the two gratings provide information about which set of bars is in front of the other. When these sources of information are consistent with each other, separation of the two gratings in depth occurs: inner line terminators no longer perceptually exist and the direction of motion becomes determined only by terminators at the edges, which causes a shift from vertical to orthogonal motion. Differences in luminance also provide (asymmetrical) information about depth relationships: when darker bars occlude lighter bars, the probability of orthogonal motion increases as a function of the difference in luminance, whereas when lighter bars are over darker bars, vertical motion prevails. PMID- 8474847 TI - The role of parts and spatial relations in object identification. AB - An investigation of the role of parts and their spatial relations in object identification is reported. At the most general level, two important results were obtained. First, proper spatial relations among components of an object are critical for easy identification. When parts were scrambled on the page, naming times and error rates increased. And, second, the way an object is divided into parts (parsed) affects identification only under the most impoverished viewing conditions. When subjects had as little as 1 s (and sometimes as little as 200 ms) to view an object, the way objects were divided into parts had no effect on naming times or accuracy. There was no hint of an interaction between type of parse and how parts were arranged on the page. This pattern of effects supports theories that suggest that objects typically are recognized without being parsed into parts. The findings are in agreement with theories suggesting that object features (not specifically related to parts) are matched directly with such features stored in long-term memory, with the constraint that the features of a single object are seen from a single viewpoint. PMID- 8474848 TI - Fast and slow blockades of the inward-rectifier K+ channel by external divalent cations in guinea-pig cardiac myocytes. AB - The present patch-clamp study shows that external Mg2+, Ca2+ and Sr2+ decrease the unit amplitude of inward current through the inward-rectifier K+ channel in a concentration-dependent manner. Sr2+ produces a voltage-dependent flickering block as well, and the fractional electrical distance between the external orifice and the Sr2+ binding site (delta) is 0.73. The decrease of unit amplitude is reversible and voltage independent while it does not increase the noise level on the open-channel current. Unit current decreased by Mg2+ or Ca2+ has a longer mean open time, which is inversely proportional to the unit amplitude. External Mg2+ does not decrease the amplitude of unit outward current. A surface potential shift, measured using voltage-dependent Cs+ block (delta = 1.60), failed to explain the current decrease. Therefore, we conclude that (1) the external divalent cations cause an extremely fast channel block, which appears as a decreased amplitude of the unit current on the recording system; (2) the blocking site (fast site) is present near the external orifice of the channel, and it is separate from the blocking site (slow site) to which Cs+ and Sr2+ bind. PMID- 8474849 TI - Demonstration of a novel apamin-insensitive calcium-activated K+ channel in mouse pancreatic B cells. AB - The whole-cell configuration of the patch-clamp technique was used to characterize the biophysical and pharmacological properties of an oscillating K(+)-current that can be induced by intracellular application of GTP[gamma S] in mouse pancreatic B cells (Ammala et al. 1991). These K+ conductance changes are evoked by periodic increases in the cytoplasmic Ca2+ concentration ([Ca2+]i) and transiently repolarize the B cell, thus inhibiting action-potential firing and giving rise to a bursting pattern. GTP[gamma S]-evoked oscillations in K+ conductance were reversibly suppressed by a high (300 microM) concentration of carbamylcholine. By contrast, alpha 2-adrenoreceptor stimulation by 20 microM clonidine did not interfere with the oscillatory behaviour but evoked a small sustained outward current. At 0 mV membrane potential, the oscillating K(+) current elicited by GTP[gamma S] was highly sensitive to extracellular tetraethylammonium (TEA; 70% block by 1 mM). The TEA-resistant component, which carried approximately 80% of the current at -40 mV, was affected neither by apamin (1 microM) nor by tolbutamide (500 microM). The current evoked by internal GTP[gamma S] was highly selective for K+, as demonstrated by a 51-mV change in the reversal potential for a sevenfold change in [K+]o. Stationary fluctuation analysis indicated a unitary conductance of 0.5 pS when measured with symmetric (approximately 140 mM) KCl solutions. The estimated single-channel conductance with physiological ionic gradients is 0.1 pS. The results indicate the existence of a novel Ca(2+)-gated K+ conductance in pancreatic B cells. Activation of this K+ current may contribute to the generation of the oscillatory electrical activity characterizing the B cell at intermediate glucose concentrations. PMID- 8474850 TI - Excess divalent cations activate Ca(2+)-mobilizing receptors in pancreatic acinar cells. AB - In single, enzymatically dissociated, rat pancreatic acinar cells, external application of excess divalent cations (Ca2+, Sr2+, Ba2+, Ni2+ and Mg2+ over 50 mM) induced Ca(2+)-dependent current responses monitored with the whole-cell recording technique. Inclusion of either EGTA, heparin or GDP[beta S] in the internal solution or treatment of acinar cells with a phorbol ester abolished the divalent-cation-induced responses. In contrast, internal inositol trisphosphate (InsP3) or GTP[gamma S] potentiated the responses. The results indicate that excess divalent cations activate membrane surface receptors or receptor/effector complexes, thereby inducing InsP3-mediated Ca2+ mobilization. The mechanism may be due to modulation of the receptors by changes in electrical profile through indirect action of divalent cations on membrane surface charges, i.e. neutralization of anionic charges. This proposal was supported by the evidence that the trivalent cation, La3+, and the polyvalent cation, protamine, both at much lower concentrations, could induce Ca(2+)-dependent responses, which were abolished by internal application of heparin, GDP[ beta S] or a high concentration of EGTA or by protein kinase C activation with a phorbol ester. PMID- 8474851 TI - Regulation and possible physiological role of the Ca(2+)-dependent K+ channel of cortical collecting ducts of the rat. AB - In the luminal membrane of rat cortical collecting duct (CCD) a big Ca(2+) dependent and a small Ca(2+)-independent K+ channel have been described. Whereas the latter most likely is responsible for the K+ secretion in this nephron segment, the function of the large-conductance K+ channel is unknown. The regulation of this channel and its possible physiological role were examined with the conventional cell-free and the cell-attached nystatin patch-clamp techniques. Patch-clamp recordings were obtained from the luminal membrane of isolated perfused CCD segments and from freshly isolated CCD cells. Intracellular calcium was measured using the calcium-sensitive dye fura-2. The large-conductance K+ channel was strongly voltage- and calcium-dependent. At 3 mumol/l cytosolic Ca2+ activity it was half-maximally activated. At 1 mmol/l it was neither regulated by cytosolic pH nor by ATP. At 1 mumol/l Ca2+ activity the open probability (Po) of this channel was pH-dependent. At pH 7.0 Po was decreased to 4 +/- 2% (n = 9) and at pH 8.5 it was increased to 425 +/- 52% (n = 9) of the control. At this low Ca2+ activity the Po of the channel was reduced by 1 mmol/l ATP to 8 +/- 4% (n = 6). Cell swelling activated the large-conductance K+ channel (n = 14) and hyperpolarized the membrane potential of the cells by 9 +/- 1 mV (n = 23). Intracellular Ca2+ activity increased after hypotonic stress. This increase depended on the extracellular Ca2+ activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474852 TI - Na(+)-dependent biotin transport into brush-border membrane vesicles from human kidney cortex. AB - Renal reabsorption of biotin was investigated in human kidney by means of the isolated brush-border membrane vesicle technique. Biotin uptake into the vesicles was sodium-dependent producing a typical overshoot when incubated under sodium gradient conditions (external concentration greater than internal). This effect was not observed in the presence of gradients of KCl, LiCl or choline-chloride, nor in the absence of any salt. Using the K+/valinomycin voltage-clamp method biotin uptake remained uninfluenced, i.e. was electroneutral, whereas glucose uptake (which is known to be electrogenic in kidney of other species) was greatly increased. When biotin transport was investigated as a function of external sodium concentration a stoichiometic coupling factor of 1 for the Na(+)-biotin- cotransport was determined. Increasing the biotin concentration in the incubation medium up to 200 mumol/l led to saturation with the kinetic parameters of 31 mumol/l for the apparent Michaelis constant and 82 nmol g protein-1 30 s-1 for the maximal transport rate. Uptake was not saturable in the concentration range of 0.001-1 mumol/l. Inhibition of the biotin uptake (25 mumol/l) was observed in the presence of 250 mumol/l dethiobiotin, bisnorbiotin, thioctic acid, and probenecid, whereas biocytin, propionic acid, lactic acid, succinic acid, citric acid, ascorbic acid, primidone and carbamazepine had no effect. We conclude that renal biotin reabsorption in human kidney is specifically sodium-dependent, saturable and electroneutral. It therefore fulfills the requirements for a secondary active carrier-mediated transport system. The results suggest that biocytin is not an inhibitor of renal biotin reabsorption. PMID- 8474853 TI - Role of microtubules in the adaptive response to low phosphate of Na/Pi cotransport in opossum kidney cells. AB - The role of microtubules and actin microfilaments in adaptive changes of the apical Na-dependent transport of phosphate (Pi) was investigated in opossum kidney (OK) cells. Up-regulation of Na/Pi cotransport was achieved by incubating OK cells in a medium containing 0.1 mM Pi; down-regulation of Na/Pi cotransport was provoked by refeeding adapted cells with 2 mM Pi. Up-regulation of Na/Pi cotransport was found to be inhibited by approximately 50% after a pretreatment of the cells with the microtubule disrupting agents nocodozole and colchicine; indirect immunofluorescence indicated complete depolymerization of the microtubular network. No inhibition of the adaptive response was observed after treatment of the cells with cytochalasin B to depolymerize actin microfilaments. In adapted cells, depolymerization of microtubules by nocodozole led to a reversibility of Na/Pi cotransport similar to that observed after refeeding adapted cells with 2 mM Pi. No effects of the microtubule disrupting drugs were observed on Na/L-glutamic acid transport. Depolymerization of microtubules did not prevent parathyroid-hormone-mediated inhibition of Na/Pi cotransport. It is concluded that microtubules are (at least in part) involved in the correct insertion of newly synthesized apical Na/Pi cotransport systems and that microtubules are not involved in the internalization of Na/Pi cotransport systems. PMID- 8474854 TI - Intracellular pH in renal tubules in situ: single-cell measurements by confocal laserscan microscopy. AB - Confocal laserscan microscopy with a dual-excitation device was used to record intracellular pH (pHi) regulation in rat proximal convoluted tubules microperfused in vivo. Cells were loaded with the pH-sensitive, fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Single cells could be distinguished within the tubules and separate measurements were possible. Application of an NH4Cl pulse by peritubular perfusion caused an immediate increase in intracellular pH. Intraluminal injection of NH4Cl led to a slower increase in intracellular pH. In both cases, cessation of perfusion led to an immediate acidification. Peritubular perfusion with 300 microM 4,4' diisothiocanatodihydrostilbene-2,2'-disulphonic acid (H2DIDS) caused an intracellular alkalinisation. Microperfusion, pH-sensitive dyes and confocal laserscan microscopy provide a new non-invasive method to measure intracellular pH effectively in individual cells of near-surface structures of the intact kidney. PMID- 8474855 TI - The Na(+)-dependence of Na(+)-activated K(+)-channels (IK(Na)) in guinea pig ventricular myocytes, is different in excised inside/out patches and cell attached patches. AB - Single Na(+)-activated K(+)-channels were recorded from intact guinea-pig ventricular myocytes perfused with Ca-free, Mg-free Tyrode, to increase [Na+]i. The activity of these channels increases with the time of perfusion with this solution and decreases when the bathing sodium is reduced. The activity of the Na(+)-activated K(+)-channel is greater in the cell attached patches than from excised cell free patches, at the same [Na+]. It is suggested that this K+ channel is significantly active in intact cells within the physiological range of [Na]i. PMID- 8474856 TI - Lymphocyte subsets recirculate from blood to lymph at different rates in conscious sheep. AB - Lymphocytes migrate and recirculate continuously between blood and lymph. The current study compared the migratory properties of lymphocyte subsets by labelling lymphocyte surface antigens and analysing simultaneous samples of mesenteric lymph, systemic arterial blood and mesenteric venous blood from conscious sheep. The lymphocyte output in lymph averaged 5.33 +/- 0.89 x 10(6) min-1 (lymph flow rate of 92 +/- 13 microliters min-1, lymphocyte count 61.9 +/- 10.7 x 10(9) l-1, n = 10) and the proportion of cells which carried the CD4 antigen (CD4+) was considerably higher in lymph (46 +/- 3%) than in arterial blood (23 +/- 2%; p < 0.01, n = 9). This increase was paralleled by a small but statistically significant decrease in the percentage of CD4+ cells in mesenteric venous blood (20 +/- 2%), as compared with systemic arterial blood (26 +/- 2%; p < 0.05, n = 6), which is consistent with the hypothesis that CD4+ cells migrate out of the blood vessels, and recirculate through the lymphatics, more readily than other lymphocyte subsets. PMID- 8474857 TI - Fast K channels are more sensitive to riluzole than slow K channels in myelinated nerve fibre. AB - The effects of 1-500 microM riluzole, a novel psychotropic agent, were studied on the nodal K current of isolated nerve fibres of the frog. When added to the external solution, the substance rapidly and reversibly inhibited slow, fast 1 and fast 2 K components of the tail K current. The concentrations of riluzole inducing half maximum reduction of slow, fast 1 and fast 2 K conductances were 413 microM, 24 microM and 21 microM respectively. It is concluded that the substance is about 20 times more effective in blocking fast than slow K channels. PMID- 8474858 TI - [CT evaluation of the pelvic cavity after total cystectomy]. AB - CT scans were performed 40 times in 28 postcystectomy patients to identify the type and location of tumor recurrence. Sixteen patients showed tumor recurrence. Patients without recurrence showed a complete symmetric pelvis and a thin string that looked like an operation scar. Cutaneous ureterostomy showed small tube-like structures, and ileal conduit looked like herniation of the ileum. Cases with recurrent tumors were divided into 3 patterns, 1) pelvic abscess recurrence, 2) anterior abdominal wall thickening, 3) pelvic lateral wall thickening, and combinations of these types. The abscess-recurrence type often showed air within the mass or a fuzzy contour that could not be differentiated from true inflammatory abscess. Anterior abdominal wall thickening was usually accompanied with abscess-type recurrence and appeared as thickening of the operation scar. Lateral wall thickening was usually seen at the site of the obturator internus muscle or obturator node. Patients without recurrence had no complaints except for two who had ileus. All patients with recurrence except one had complaints of pain, abnormal secretion, or a palpable mass. Because all patients with recurrence already had a relatively large tumor at the time of CT, routine follow up CT is recommended even if the patient has no complaints. PMID- 8474859 TI - [Avascular necrosis of the femoral head: staging by MR imaging]. AB - Magnetic resonance (MR) images and conventional radiographs were compared in 142 hips with avascular necrosis, and a staging system for the disease based on MR imaging was developed. MR images were classified into three patterns: class I: a band of low signal intensity, class II: an area of low signal intensity with internal spot (s) of high signal, and class III: an area of low signal intensity without internal spots of high signal. Most MR class I lesions were in radiographic stage I (normal) or II (sclerotic or cystic changes without collapse). Most MR class II lesions were in radiographic stage III (segmental collapse), and most MR class III lesions were in stage III or IV (secondary degenerative changes). The MR image classification was closely correlated with radiographic staging (p < 0.01, using chi square test). We considered that this classification closely reflected the different stages of the disease according to the histopathology of the bone marrow. PMID- 8474860 TI - [Reappraisal of the clinical usefulness of transabdominal ultrasonography for advanced colon cancer--a study of tumor detection]. AB - We evaluated the detectability of colon cancer by using transabdominal ultrasonography (US). Fifty-three cases of proven advanced colon cancer were examined in this study. Screening by US was carried out in 27 of 53 cases and US was performed in all cases after the definite diagnosis. Lesions of the colon were examined by using a 3.5 MHz convex and 5 MHz or 7.5 MHz linear probe (Yokogawa RT-2800, RT-4600). Localized hypertrophy of the irregular wall of more than 10 mm or massive tumor without the normal layered structure was defined as colon cancer on US. The rate of detection by screening test was 52%. The detection rate by US after definite diagnosis was 75%. A high detection rate was obtained in cases with a tumor diameter of more than 4 cm. Eight of 13 cases which were not detected by the screening test were visualized by US after definite diagnosis. US examination is useful for the detection of certain extended lesions of colon cancer. With technical improvements of the examination method, it is considered that cancer in the gastrointestinal tract may be discovered early on screening tests using US. PMID- 8474861 TI - [Sequential MR images of the uterus after Gd-DTPA injection--studies of normal volunteers and uterine endometrial malignant tumors]. AB - To investigate the sequential changes in signal intensity (SI) of normal and abnormal uteri, T1 WIs were taken repeatedly after the injection of Gd-DTPA. Six volunteers and 19 patients with known uterine body malignancy (18 carcinomas, one carcinosarcoma) were examined. The results in volunteers were as follows. In the secretory phase, SI of the endometrium was stronger in the late images than in the early ones, whereas in the proliferative phase, SI was stronger in the early images. SI of the myometrium decreased rapidly and there were no differences in SI between menstrual phases. In 17 of 18 endometrial carcinomas, the tumors showed hypointensity relative to the myometrium, and the contrast between the tumor and the myometrium was better in the early images. In the remaining two cases, the tumor showed hyperintensity and the contrast was better in the late images. After the injection of Gd-DTPA, the endometrium appeared differently according to the menstrual cycle in normal volunteers, and the appearance of uterine structures and endometrial malignant tumors changed sequentially. These findings must be kept in mind when evaluating uterine diseases by Gd-DTPA enhanced MRI. PMID- 8474862 TI - [CT findings of diffuse pleural disease--alteration of pleura and extrapleural fat]. AB - This is a comprehensive study on the usefulness of CT in the evaluation of diffuse pleural diseases in 114 patients. Alterations of the pleura and extrapleural fat were analyzed. The pleural changes were classified into five groups: no thickening (group 1), focal thickening (group 2), diffuse smooth thickening (group 3), diffuse nodular thickening less than 10 mm (group 4), diffuse nodular thickening more than 10 mm (group 5), CT findings of group 1 were mostly found in patients with transudatory effusion; group 2 in all patients with asbestosis; group 3 in those with empyema; and group 4 and 5 in those with malignant pleural diseases. In some cases with malignant pleural diseases and asbestosis, mediastinal and/or fissural thickening was present. Circumferential pleural thickening (pleural rind) was only seen in malignant pleural diseases. Pleural calcification was present in chronic empyema and asbestosis. Increased thickness of the extrapleural fat was seen in malignant pleural diseases and empyema, but homogeneous increased attenuation of the extrapleural fat might be a specific finding in acute empyema. The author concludes that CT is useful in the evaluation of pleural changes and alterations of extrapleural fat with diffuse pleural diseases, particularly in the pattern recognition based on CT classification. PMID- 8474863 TI - [The assessment of tumor blood flow factors using dynamic CT--a comparison with positron emission tomography]. AB - The dynamic computed tomography (CT) was performed by using rapid-sequence scanning following an intravenous bolus injection of contrast material. Time density curve was applied for Gamma variate curve fitting and CT attenuation values were applied for two compartment model. The value of 1/CM, k1 and k2 were defined as the blood flow factors in this study. The inhalation of C15O2 using positron emission tomography (PET) can be useful for determining regional tumor blood flow (rBF). CT and PET were performed in twelve patients. The diagnosis was malignant lymphoma in four, and others; two liver metastasis, one focal nodular hyperplasia of the liver, one dermatofibrosarcoma, one hepatocellular carcinoma, one malignant melanoma, one malignant meningioma, one bone metastasis. The correlations among rBF, 1/CM, and k1 were good, and better correlations were obtained among tumor blood flow factors and rBF in the case of the tumors which existed far from air way and/or had low blood flow. The distance from air way effected both the value of rBF and tumor blood flow factors. Both the distance from air way and pathology caused conflicting results between rBF and tumor blood flow factors. Dynamic CT was particularly useful for evaluated the blood flow of tumors that had contact with air way. PMID- 8474864 TI - [Radiotherapy for vulvar cancer]. AB - Fifteen patients who had primary vulvar cancer treated with radiotherapy as an initial treatment at Hyogo Medical Center for Adults and Hyogo Cancer Center from January 1971 to December 1990 are presented. Two patients were stage 0, one stage I, three stage II and nine stage III. Nine patients received electron irradiation with or without interstitial irradiation and intracavitary vaginal irradiation. Five patients received megavoltage X-ray irradiation using AP/PA parallel opposed fields including the pelvic nodes and perineum followed by boost irradiation of electrons, interstitial irradiation and intracavitary vaginal irradiation. The total dose delivered to the primary tumor ranged from 50 to 100 Gy (73 Gy on average). The actuarial 5-year survival rate of the patients was 43.6%. Complete regression (CR) was achieved in 60% of the patients. However, CR was not achieved in any of five patients with palpable inguinal nodes. In contrast, all the patients who had tumors of less than 2 cm in diameter achieved CR. Five of nine CR cases relapsed. First sites of failure were vagina, groin and vulvar region. Recurrence occurred more than four years after treatment in three cases. Necrosis occurred in five of nine CR cases. PMID- 8474865 TI - [Discarding medical images and its evaluation]. AB - Following a survey of our filing system, the period of storage of medical images was generally limited to ten years, a system which was put into execution in 1990. Film jackets older than ten years are discarded every year, except for those registered for permanent storage. Fourteen thousand jackets (6.5% of total) have been registered for permanent storage. A follow-up survey has been performed to evaluate this system. The survey focused mainly on the frequency of re-issue of film jackets, and the rate of access to jackets. Discarded jackets now number about 50,000, a reduction of 20%. A total of 405 jackets were re-issued in a year due to the re-examination of patients whose jackets had been discarded. The annual number of re-called jackets from the repository outside our hospital was about 2,200 (about 500 of them were for research work), which corresponded to 1.5% of the patients re-examined in the radiology department. The new filing system has been well integrated into the hospital daily routine. Information cost was calculated as a function of access rate to the stored information, and the concept of "cost-of-information" was proposed as a measure of cost analysis of an information system. PMID- 8474866 TI - [Carbon beam irradiation of monolayer cells]. AB - This study was performed to determine the biological effect of carbon beams on mammalian cells (HeLa, RMUG), in comparison with 200 KVp X-rays. Carbon beams were generated by the Riken Ring Cyclotron. An increase in the relative biological effect (RBE) was observed in both cell lines as the LET of the carbon beam increased between 20 and 80 keV/microns. The RBE depended on the size of the irradiation dose at the higher LET region, and increasing the dose from 0.8 Gy to 3.2 Gy decreased the RBE from 2.9 to 2.7. The survival curves of cells irradiated with 20 keV/microns carbon beams showed an initial shoulder. When RMUG was irradiated at 4 Gy with 200 KVp X-rays, the recovery rate between two split doses (6 hour interval) was 1.7. RMUG irradiated with 20 keV/microns carbon beams (4 Gy) showed a recovery rate of 1.4. Recovery between split dose irradiation was observed with both X-ray and carbon beam irradiation; however, the recovery rate was lower with carbon beams. Cells irradiated with LET higher than 40 keV/microns did not show recovery between split doses. PMID- 8474868 TI - Simple technique for placement of Palmaz stent. PMID- 8474867 TI - [The correlation between the rise of tumor temperature during hyperthermia treatment and tumor blood flow measured by dynamic CT and 15 O gas-positron emission tomography]. AB - This study was designed to determine the correlation between the rise of tumor temperature during hyperthermia treatment and the blood flow of the tumors measured by dynamic CT (DCT) and 15Ogas-positron emission tomography. In this report, we observed 20 patients with malignant tumors which underwent hyperthermia treatment. In each case, the temperature of the tumor was monitored with a photofiber sensor. DCT's and 15Ogas-positron emission tomographies were applied before the hyperthermia treatment. During the DCT, the tumor blood flow of each tumor was estimated by by analyzing the time-dependent activity curve after a bolus injection. During the 15Ogas-positron emission tomography, the tumor blood flow was estimated by the C15O2-steady-state method. The value of the tumor blood flow estimated by DCT were proportional to those calculated by the 15Ogas-positron emission tomography. These values were inversely proportional to the rise of the temperature of the tumors during hyperthermia treatment. Our results imply that DCT as well as the 15Ogas-positron emission tomography can be used for the prediction of the tumor temperature rise during the hyperthermia treatment. PMID- 8474869 TI - [Evaluation of EC-IC bypass flow by MR angiography using the presaturation technique]. AB - MR angiography studies using the presaturation technique were performed in 7 patients who had received extra-intracranial (EC-IC) bypass surgery. With presaturation on the bypass vessels, disappearance of intracranial vascular signals suggests bypass effect. In our studies, good bypass effect was shown in 3 cases and poor effect in 2 cases, which correlates well to concurrent angiography. In two cases, bypass effect was shown only in a few cortical branches of MCA, but angiography confirmed recanalization of occluded internal carotid artery in one case, and growth of large network of transdural anastomoses in the other. PMID- 8474871 TI - What can just one nurse do? PMID- 8474870 TI - [A study of transsplenic CO2 gas enhanced portal angioechography]. AB - Transsplenic CO2 gas enhanced portal angioechography was examined. The spleen of three dogs was punctured by 23 gauge needle with two side holes. From 5 ml to 20 ml of CO2 gas was injected into the splenic vein via the splenic parenchyma, and elevation of echo level of the liver was observed. Hematoma was not seen at the site of puncture. Good image was obtained in the case of 5 ml CO2 injection. In one dog with pseudotumor in the liver, the hyperechoic tumor changed into negative enhanced nodule after CO2 gas enhancement. Transsplenic CO2 gas enhanced portal angioechography is thought to be useful to evaluate hepatic tumors. PMID- 8474872 TI - Health care reform: one view of the future. PMID- 8474873 TI - Nursing research with African American and Hispanic people: guidelines for action. AB - In this article we have noted some of the conceptual and methodologic issues and challenges involved in conducting research with two ethnic/racial populations. In addition, we raised questions and gave recommendations to provide nurse researchers with guides as to how they might conceptualize and conduct and critique research with two groups. While this is not a strict blueprint, it is hoped that the guidelines and recommendations will serve as a focal point about which continued discourse and critical thinking about conducting research with members of ethnically/racially diverse groups may occur. The complex issues presented are not unique to nursing. Researchers from various disciplines have enumerated similar issues and, in turn, have been critical of research findings with samples of ethnic/racial groups. While a cadre of nurse researchers has begun to accept the challenge and to struggle with issues, more--much more--is needed. Conducting research with racial/ethnic minority populations in general, and African American and Hispanic peoples in particular, is necessary if nursing is to fulfill its societal mandate. Historically the scientific base for nursing practice has been described as being deficient in areas associated with cultural diversity. Few studies with deliberate cross-cultural or multicultural foci exist. According to Stevenson, laws of health and nursing must be constructed from research conducted with people of multiple cultures so that generalizations about health are valid representations of existing realities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474874 TI - Laying claim to caring: nursing and the language of training, 1915-1937. PMID- 8474875 TI - Returning to work after childbirth: considerations for health policy. PMID- 8474876 TI - Nursing theory in perspective. PMID- 8474878 TI - Nursing Times open learning programme. M6: managing the process of providing care. Part (iii): Using appropriate resources (continuing education credit). PMID- 8474877 TI - Violence as a nursing priority: policy implications. AAN Expert Panel on Violence. PMID- 8474879 TI - Study reveals isolation and strain in HIV/AIDS workers. PMID- 8474880 TI - Animal rites. PMID- 8474881 TI - Trust betrayed. PMID- 8474882 TI - A private matter. PMID- 8474883 TI - Ticket to ride. PMID- 8474884 TI - Market forces. PMID- 8474885 TI - Goodwill or hard sell? PMID- 8474886 TI - Conflicting interests? PMID- 8474887 TI - Understanding anti-emetics. PMID- 8474888 TI - Safety net. PMID- 8474890 TI - Behavioural challenge. PMID- 8474889 TI - He, she or it? PMID- 8474891 TI - Systems of life. The nervous system. 6. PMID- 8474892 TI - The journal of infection control nursing. Auditing problems. PMID- 8474894 TI - Management module. M7: evaluation. Part (ii): The practice of evaluation. PMID- 8474893 TI - The journal of infection control nursing. Supply-side support. PMID- 8474895 TI - Confidentiality paramount in occupational health department. PMID- 8474896 TI - Tact urged on gender change. PMID- 8474897 TI - Vital support. PMID- 8474898 TI - Choice in childbirth. PMID- 8474899 TI - Rebel Rowden. Interview by Andrew Cole. PMID- 8474901 TI - Body politic. Reviews review. PMID- 8474900 TI - Voice of concern. PMID- 8474902 TI - Community Care Act. We have lift off!. Interview by John Gilbert. PMID- 8474903 TI - Community Care Act. United in uncertainty. PMID- 8474904 TI - Ward organization. Beating time. PMID- 8474905 TI - Professional development. The chosen few. PMID- 8474906 TI - Insignificant others? PMID- 8474907 TI - Teamwork. Joint account. PMID- 8474908 TI - Live issues--a practical response. PMID- 8474909 TI - Patient education. Achieving patient compliance. PMID- 8474910 TI - Wound care. Healing the whole person. PMID- 8474911 TI - Wound care. Basing care on research. PMID- 8474912 TI - Wound care. Preventing infection. PMID- 8474913 TI - Wound care. Using air fluidised therapy. PMID- 8474914 TI - Wound care. Comparative benefits. PMID- 8474916 TI - Dangerous world. PMID- 8474915 TI - What makes the marketplace such a good template for NHS? PMID- 8474917 TI - Regional cuts. PMID- 8474918 TI - Moores' code. Interview by Daloni Carlisle. PMID- 8474919 TI - Qualified excess? PMID- 8474920 TI - Patient's Charter--charting progress. PMID- 8474922 TI - Patient's Charter--power to the people? PMID- 8474921 TI - Patient's Charter--name-check. PMID- 8474923 TI - Making sense of mini-tracheostomy. PMID- 8474924 TI - Infection control. Born in the USSR. PMID- 8474925 TI - Live issues--invested interest. PMID- 8474926 TI - Live issues--a healthy balance. PMID- 8474927 TI - Accident prevention--safe as houses. PMID- 8474929 TI - At home with stoma care. PMID- 8474928 TI - Nursing development units. Division of labor. PMID- 8474930 TI - Stoma care--what can I eat? PMID- 8474931 TI - On the road--driving a hard bargain. PMID- 8474932 TI - On the road--policy decisions. PMID- 8474933 TI - Therapeutic decisions: assessing clinical fit. AB - Quality health care has been defined as the maximization of desired outcomes while minimizing undesirable consequences. Therefore, the optimal antimicrobial agent for a given clinical condition will be one that is the most rapidly effective, produces the least patient discomfort, results in minimal disruption of the patient's or hospital flora, and causes minimal dissatisfaction with the treatment program and its attendant costs. The clinical utility of antimicrobials is generally judged on the basis of in vitro activity, kinetic disposition, resistance trends, safety, and cost. Fluoroquinolones possess characteristics in each of these areas; for example, broad, potent gram-negative spectrum coupled with excellent oral absorption and tissue penetration, and relative safety and reduced cost compared with parenteral therapy. Drawbacks include the emergence of resistance among certain bacteria, particularly staphylococci and Pseudomonas aeruginosa, drug interactions that may compromise efficacy, and greater cost than other potentially useful oral antimicrobial agents. Indications for the agents' use can be categorized as appropriate (gram-negative osteomyelitis, complicated urinary tract infection, prostatitis, certain sexually transmitted diseases, bacterial gastroenteritis), potential (gastrointestinal tract decontamination in granulocytopenic patients, exacerbations of chronic obstructive pulmonary disease, nosocomial pneumonia and bacteremia, eradication of certain bacterial carrier states), or inappropriate (community-acquired pulmonary infections, especially aspiration pneumonitis, serious gram-positive infections, uncomplicated urinary tract infection, surgical prophylaxis except prostatic surgery). Gram-negative osteomyelitis serves as a model to demonstrate the fluoroquinolones as agents for quality health care. Current and future investigations should focus on the cost effectiveness and cost utility of the agents. PMID- 8474934 TI - Drug-drug interactions with fluoroquinolones. AB - Antimicrobials of the fluoroquinolone class are involved in a number of clinically important drug-drug interactions. Many of these interactions occur with all the available agents and exhibit little interpatient variability. In contrast, others occur only with specific fluoroquinolones and their extent varies markedly among subjects. The oral absorption of all fluoroquinolones is significantly impaired when coadministered with aluminum- and magnesium containing antacids and sucralfate, as well as with other metal cations such as calcium and iron. Concomitant use of these agents, even when dosed several hours apart, should be avoided. Enoxacin and ciprofloxacin impair the hepatic metabolism of theophylline and caffeine, leading to significantly increased serum concentrations. Ofloxacin and lomefloxacin have only minimal effects on xanthine metabolism. Case reports suggest that concomitant administration of several fluoroquinolones and warfarin, a drug that is also highly metabolized by the liver, leads to increased hypoprothrombinemic effects; prospective studies, however, failed to confirm this interaction. Clinicians must be aware of these and other potential drug-drug interactions with fluoroquinolones for optimal use of the agents. PMID- 8474935 TI - Maximizing patient outcomes of antiinfective therapy. AB - Drug treatment of infectious disease requires consideration of both short- and long-term therapy. Although in most settings patients receive antimicrobials for acute events, long-term management of certain infections with drugs that delay progression of the disease adds a new facet to pharmacotherapy. In the past, broad questions regarding efficacy were posed: a drug was evaluated as either effective or not effective for a particular disorder. The actual question is, in whom is a given drug at a given dosage effective? Antibiotic control, restriction, and pharmacokinetic dosing programs have been useful, but they are reactive as opposed to proactive. The expensive products of biotechnology and the availability of oral drugs with activity exceeding that of parenteral antimicrobials require a more expanded scope of clinical pharmacy practice where patients are identified for these therapies prospectively using statistical models based on disease and other readily identified factors. Predictor variables for patient outcomes such as retreatment with other antibiotics, rehospitalization, toxicity, and mortality following the use of new drugs should be identified. Maximizing these outcome measurements will involve strategies that integrate epidemiology and statistical modeling techniques with principles of pharmaceutical care. PMID- 8474936 TI - Pharmacokinetic considerations in quinolone therapy. AB - It is advisable to switch patients from parenteral to oral therapy as soon as practical. High volumes of distribution, coupled with relatively low protein binding, indicate that the quinolones are widely distributed outside extracellular fluid. Interactions with aluminum- or magnesium-containing antacids may be avoided by administering the antacids at least 2 hours after quinolone dosing. Some quinolones with high bioavailability (e.g., ofloxacin) are absorbed as reliably and completely after oral administration as when given parenterally, and dosage adjustments for these agents are unnecessary after sequential therapy. Treatment strategies may differ according to the route of drug elimination, and dosage adjustments are required in patients with renal failure who receive quinolones excreted primarily by the kidneys. Theophylline interactions may be more problematic in patients given quinolones that are primarily metabolized by the liver. Quinolones, which have concentration-dependent killing and a long postantibiotic effect, should be administered in the highest tolerated dosage. A method to assess the relative antibacterial efficacy of the quinolones uses the ratio of the Cmax:MIC90 of the organism, compared with a ratio derived from the NCCLS breakpoints for susceptibility. PMID- 8474937 TI - Prescribing considerations in fluoroquinolone therapy. AB - Comparative trials have shown that the new oral fluoroquinolones are as effective as parenteral cephalosporins and other broad-spectrum agents in treating infections of the urinary tract, lower respiratory tract, and skin and skin structure caused by most gram-negative and selected gram-positive pathogens. The agents are also effective in the treatment of prostatitis and osteomyelitis. Sequential parenteral to oral therapy has also proved useful, even in patients who are severely ill and are in intensive care units. This allows patients to be transferred out of intensive care earlier, reduces hospital stay and pharmacy costs, and improves quality of life. Because of the high bioavailability (> 95%) of ofloxacin, oral and parenteral doses are identical. PMID- 8474938 TI - Diagnosis and treatment of community-acquired and hospital-acquired pneumonia. AB - The older drugs used to treat pneumonia may still be useful in self-limiting infections. Newer antibiotics--augmented penicillins, trimethoprim sulfamethoxazole, third-generation cephalosporins, and others--are quite effective, but resistance can be a problem, and some patients cannot tolerate the adverse events associated with these agents. The fluoroquinolones are effective in treating pneumonia because of their broad spectra of activity against gram negative and gram-positive organisms, including Streptococcus pneumoniae and Haemophilus influenzae. They are rapidly and nearly completely absorbed after oral administration; bioavailability ranges up to 100% for ofloxacin and lomefloxacin. Concentrations attained in lung tissues and sputum generally exceed the minimum inhibitory concentrations for the most common respiratory tract pathogens. The quinolones are also well tolerated; most adverse events are mild and do not lead to discontinuation of therapy. Ciprofloxacin and ofloxacin are available in parenteral as well as oral formulations. The high bioavailability of oral ofloxacin (> 95%) allows a patient to be started on the parenteral form in the hospital and continued taking the oral form at home with no loss of efficacy, but with reduced costs and improved quality of life. PMID- 8474939 TI - Urinary tract infections in the elderly. AB - Urinary tract infection (UTI) is the most common infectious disease of the elderly and is especially prevalent in debilitated, institutionalized older individuals. Unlike UTI in younger women, which tends to be related to frequency of sexual intercourse and is uncomplicated, in the elderly it is more difficult to treat and its pathogenesis is related to abnormal bladder function, bladder outlet obstruction, vaginal and urethral atrophy, use of long-term indwelling catheters, and puddling related to bed rest. The spectrum of organisms causing infection relates to the ecology of the patients' environments; those residing in nursing homes and especially with permanent indwelling catheters tend to have a greater variety of pathogenic organisms, many of which may be relatively antibiotic resistant. Short-course antibiotic therapy is less effective in older patients, and relapse or recurrence is more common regardless of the duration of treatment. Asymptomatic bacteriuria is common in older patients with abnormal bladder function. The clinical significance of asymptomatic bacteriuria generally is minor, and treatment is not beneficial. PMID- 8474940 TI - Developing drug use evaluation criteria for parenteral fluoroquinolones. AB - The basic tenet of pharmaceutical care asserts that the delivery of optimal, cost effective pharmacotherapy can be best achieved by identifying, resolving, and preventing drug-related problems. Drug use evaluation (DUE) is one of the primary tools used to achieve these ends. Fluoroquinolone antimicrobials meet Joint Commission criteria for targeting for DUE: the drugs are used in populations at high risk for adverse drug reactions, quality assurance or infection control committees target them for DUE, the drugs are costly, they may be suspected or known to be used inappropriately, and they are prescribed frequently. Outside this supplement, no published DUE criteria for parenteral fluoroquinolones currently exist. Suggested criteria include use in patients who would otherwise be candidates for oral fluoroquinolone therapy (for which published criteria exist) but who cannot use the oral route of administration due to gastrointestinal conditions predisposing to malabsorption or unavailability of the oral route; for severe infections due to gram-negative pathogens; as a replacement for aminoglycosides when ototoxicity or nephrotoxicity is a substantial risk; targeting to resistant pathogens (i.e., not as empiric therapy); and targeting to therapeutic use only (not for prophylaxis). The DUE process is crucial for ensuring safe, effective, appropriate, and economical drug therapy. It is an effective mechanism for evaluating the use of new agents and as an educational tool for clinicians in the postmarketing period. PMID- 8474941 TI - Criteria for the use of intravenous ofloxacin in hospitalized adult patients: drug use evaluation guidelines. PMID- 8474943 TI - The digital revolution and patient self-empowerment. PMID- 8474942 TI - Pharmaceutical care and specialty practice. AB - The practice of pharmaceutical care is a possible goal for all pharmacists' professional maturation. Six issues exist in which pharmaceutical care may represent a radical departure from some contemporary clinical practices. Because no profession is capable of providing pharmaceutical care singlehandedly at an acceptable level of quality, it is necessary to construct systems that organize the necessary variety of professionals and patients for managing drug therapy. In such a system, pharmacists can organize specialty practice around a strong general practice of pharmacy that is able to coordinate drug therapy and manage for outcomes, organize around the practice of medicine as if pharmacy were a medical specialty, or merge into the organization of a hospital or other healthcare organization. PMID- 8474944 TI - The effect of training staff in office-based smoking cessation counseling. AB - A role for office staff members in smoking cessation counseling has recently been recognized and encouraged. We studied the impact of physician-staff team training in office-based smoking cessation counseling on staff members in 35 practices in Raleigh, North Carolina. Staff members who attended an educational meeting were compared with two groups: other staff members in their practices who did not attend the meeting and staff in other practices in which no one attended the meeting. Baseline attitudes toward and participation in smoking cessation activities were not significantly different among the three groups. Four months after the training, staff who had personally attended the meeting reported greater involvement in counseling activities than either of the two comparison groups. Attitudes toward involvement in counseling activities did not change significantly over the study period. Training staff members in office-based smoking cessation counseling may be a useful step toward increasing staff participation in these activities. PMID- 8474945 TI - Patient and physician perceptions of their relationship and patient satisfaction: a study of chronic disease management. AB - This study investigated patient and physician perceptions of their relationship and examined how their perceptions related to patient satisfaction. Data are based on 134 patient-physician interactions. Study participants included 12 physicians (five women and seven men) and 134 male patients with a diagnosis of diabetes mellitus being seen on an outpatient basis. Information on patient and physician demographics, patient's metabolic control and functional status and time spent in the interaction were also collected. Results revealed that patients with lower levels of education were most satisfied and that physicians who viewed the relationship as a patient-physician partnership had more satisfied patients than those who viewed the relationship as physician controlled. Findings also indicated that physicians' gender and number of years in practice were not related to patient satisfaction. Practical implications include: (1) increasing attention to physician's perceptions of his or her relationship with individual patients and (2) exposing newly trained physicians to partnership types of relationships, if future research confirms these findings in chronic disease management. PMID- 8474946 TI - Promoting preventive care with patient-held minirecords: a review. AB - Although patient involvement is essential for the success of all types of preventive care, patient involvement in clinical prevention has been limited. Patient-held minirecords have recently received support from public health authorities, providers and the public as a means to improve patient involvement in preventive care for adults. This paper reviews the history and current developments in patient-held minirecord use for preventive care. METHODS: A literature review was performed using sources obtained from electronically searching the Medline database from 1966 to the present and using reference lists to obtain secondary sources. The author's collection of privately and governmentally produced minirecords was also utilized. FINDINGS: Patient-held minirecords have been widely and successfully employed to improve preventive care for children, particularly with regard to immunizations. They have not been widely used to promote adult preventive care. Several clinical trials have found that their use can lead to improved preventive care for the general adult population. Potential advantages of patient-held minirecords include: improved performance rates of preventive care, improved continuity of preventive care, low cost and improved practice promotion for prevention-oriented providers. Potential barriers to the use of patient-held minirecords include: the traditional power relationship of physicians and patients, physicians' reticence to share records with patients and time and effort costs. The optimal characteristics of a patient held minirecord for adult preventive care remain to be delineated by research and evaluation. SIGNIFICANCE: A patient-held minirecord is an inexpensive, practical intervention that can help build patient involvement and improve the quality of preventive care for adults as well as children. PMID- 8474947 TI - Idiopathic hydropericardium as a cause of death of a preterm neonate. AB - We report a case of a very premature infant who died on day 17 of life because of clinically unsuspected cardiac tamponade due to a pericardial effusion with no gross or microscopic features of myocardial inflammation or perforation. The pericardial effusion probably accumulated for 8 days prior to his death, as evidenced by chest X-ray films. The only relevant microscopic finding was a prominent pericardial and myocardial interstitial edema. Although Staphylococcus epidermidis line sepsis, central venous catheter trauma, hypoalbuminemia, anemia, and heart failure could be possible contributory factors, no definitive cause of the pericardial effusion was found and the etiology of this condition remains obscure. PMID- 8474948 TI - Antenatal cerebral necrosis in monochorionic twins. AB - Antenatal cerebral white matter necrosis occurs relatively frequently in monochorionic twins, particularly when one twin has died in utero or in the twin twin transfusion syndrome. A case of antenatal cerebral necrosis in both of liveborn monochorionic twins is presented. It is proposed that placental artery to-artery or vein-to-vein anastomoses may predispose twin fetuses to hemodynamic instability. Fluctuations in blood pressure or blood volume may then result in cerebral necrosis, without requiring the death of one twin or transfer of a blood borne factor from one twin to the other. PMID- 8474949 TI - Metastasizing cervical teratoma of the fetus. AB - We present one case with a metastasizing cervical teratoma in a newborn infant who died of respiratory failure due to extensive cervical tumor masses and multiple pulmonary tumor metastases. This case provides evidence that very rarely malignant behavior may occur in congenital cervical teratomas, the prenatal diagnosis of which may be important for any further therapeutic management. PMID- 8474950 TI - Limb reduction defects--autopsy study. AB - We present a case-control study of limb reduction defects taken from autopsy material of the Pathology Department of the University of Athens from the year 1986 to 1990. During this period 1725 perinatal autopsies were performed, in which 34 neonates were found to have had a limb reduction defect (LRD) (1.97%). The cases were divided into five subgroups: transverse, intercalary longitudinal, split, and multiple types of LRD. Of all the cases, 44.17% involved the upper limb, 41.17% the lower limb, and 14.70% both. Coexisting nonlimb malformations were found in 17 cases (50%), 5 with recognized syndromes and 12 with other associated defects. Risk factors correlated with LRD were found to be low birth weight (2500 g or less) and threatened abortion. PMID- 8474951 TI - Gastroesophageal reflux and sudden infant death syndrome. AB - The possible role of gastroesophageal reflux in the pathogenesis of the sudden infant death syndrome (SIDS) has not yet been clearly defined, although it does appear that infants with significant reflux are at greater risk of respiratory complications. A study was undertaken to characterize more precisely the histological features of esophageal mucosa taken from a series of infants who died of SIDS to determine the range of changes present. Full-length strips of mucosa were examined microscopically for reflux-related changes of basal layer hyperplasia, papillary elongation, and intraepithelial eosinophilia. Eight infants (21%) showed changes considered diagnostic of reflux esophagitis, 17 infants (45%) showed minor nondiagnostic changes, and 13 infants (34%) showed no histologic abnormalities. These findings demonstrate considerable morphological heterogeneity in a group of infants presenting with sudden and unexpected death. The absence of, or presence of only very minor, pathological alterations within the esophageal mucosae of 79% of infants suggests that reflux of a degree sufficient to cause diagnostic histologic changes is found in only a minority of infants presenting with SIDS. PMID- 8474952 TI - Histological investigations into the relationship between low birth weight and spontaneous bowel damage in the neonatal piglet. AB - Experimental models for the study of neonatal necrotizing enterocolitis (NEC) using the small for gestational age (SGA), viable, term-delivered piglet have recently been described. A spontaneous model, especially of the early phases of NEC, has not been reported. Pig litters usually include one or two lethally or sublethally SGA "runted" piglets culled from the litters by breeders. We have examined four groups of piglets: group A, SGA, lethally runted animals who died spontaneously before 12 h postpartum; group B, SGA, sublethally runted animals, showing some signs of vitality and left alive for 24 h before culling; group C, appropriate for gestation age (AGA) animals subjected to hypoxia and hyperviscosity known to induce NEC-like lesions; and group D, AGA control animals. Acute, multiorgan pathology common to pre- and dysmature neonates was seen in groups A and B. Animals in group B also showed evidence of early postnatal complications such as urinary tract infection and diffuse pulmonary damage. All animals of groups A and B showed unequivocal early changes in the distal ileum, with mucosal and submucosal necrosis, suggestive of ischemic injury. One animal in group B had developed mural necrosis involving the whole of the submucosa. No similar changes were seen in control group D animals. The very SGA, lethally and sublethally runted, spontaneously term-delivered piglet offers sufficient spontaneous early NEC-like changes for studies of the early pathogenesis of this condition. PMID- 8474953 TI - Intrathyroidal parathyroid. AB - Fifty-eight human fetal thyroid glands obtained at autopsy were systematically studied for the presence of intrathyroidal parathyroid tissue. The latter was found in 13 thyroid lobes from 12 fetuses. It was located in a subcapsular position in 9 of 58 cases and lying deep in thyroid tissue in 4 of 58. Our findings suggest that intrathyroidal parathyroid tissue is not such a rare finding and should always be considered especially for the clinical and surgical management of patients with primary hyperparathyroidism due to parathyroid hyperplasia. PMID- 8474954 TI - Polymerase chain reaction facilitates archival autopsy studies of sickle cell disease. AB - Archival autopsy studies of sickle cell disease have often been hampered by inadequate documentation of the genotype. Although the polymerase chain reaction (PCR) has been applied to the prenatal diagnosis of sickle cell disease, its use has not been reported in archival studies of sickle cell disease. In this study, DNAs from formalin-fixed, paraffin-embedded archival tissues were amplified by PCR and analyzed by dot-blot hybridization using allele-specific oligonucleotides. These S and C genotypes for 9 of 10 archival specimens studied blindly were correctly identified by PCR. The tenth specimen consistently failed to amplify by PCR, yielding no result. These data demonstrate the utility of PCR for retrospective identification of the genotype of sickle cell disease. This application of PCR will significantly expand the number of autopsy cases suitable for retrospective studies of the morbidity and mortality of sickle cell disease. PMID- 8474955 TI - Contemporary approaches toward understanding the pathogenesis of Hirschsprung disease. AB - Hirschsprung disease (HD), or congenital aganglionosis coli, is a birth defect with heterogeneous causes. In an effort to understand the molecular and cellular bases for this disorder, researchers have investigated enteric neurodevelopment in normal animals and compared these findings with observations of inbred animal strains that develop aganglionosis coli due to mutations at specific genetic loci. Recent technological advances, including use of retroviral and fluorescent lineage makers, immunohistochemical probes, and transgenic mice, have provided insights into the origins, behavior, and properties of enteric neuroblasts. Experiments with mutant murine embryos indicate that aganglionosis coli results from primary failure of neural crest-derived neuroblasts to colonize the distal colon. In at least one model, impaired colonization by neuroblasts may be secondary to environmental defects restricted to colonic mesenchyme. The discovery that human piebald trait, a hereditary disorder with a high incidence of HD, is caused by mutations in a growth factor receptor highlights the importance of regulatory intercellular interactions between nonneuroblastic mesenchyme and neuroblasts during normal development of the enteric nervous system. These observations, coupled with advances in molecular genetics, set the stage for dramatic progress in this field of research in the near future. PMID- 8474956 TI - Nonimmune hydrops fetalis, hydramnios, microcephaly, and intracranial meningeal hemangioendothelioma. AB - Necropsy findings in a male stillborn at 31 weeks gestational age included nonimmune hydrops, hydramnios, and microcephaly secondary to a hemangioendotheliomatous malformation at the tentorium. The vascular lesion was composed by large and small tortuous endothelium-lined vessels and leiomuscular septa. The lesion is thought to be related to the more frequent arteriovenous malformation of the vein of Galen. PMID- 8474957 TI - Can methylmercury present in fish affect human health? PMID- 8474958 TI - The effects of cyclic imides on lipid absorption from the intestine and on bile lipids and bile acids of Sprague Dawley rats. AB - The cyclic imides, o-(N-phthalimido)acetophenone, 2,3-dihydrophthazine-1,4-dione and N(4-methyl phenyl)diphenimide, were evaluated for their effects on bile lipids, bile acids, small intestinal absorption of cholesterol and cholic acid and liver and small intestinal enzyme activities involved in lipid metabolism. The agent at 20 mg/kg/day orally elevated rat bile excretion of lipids, e.g. cholesterol and phospholipids, and increased the bile flow rate. These agents altered the composition of the bile acids, but there was no significant increase in lithocholic acid which is most lithogenic in rats. The three agents did decrease cholesterol and cholic acid absorption from isolated in situ intestinal duodenum loops in the presence of drug. Hepatic and small intestinal mucosa enzyme activities, e.g. ATP-dependent citrate lyase, acyl CoA cholesterol acyl transferase, cholesterol-7-alpha hydroxylase, sn-glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase, and lipoprotein lipase were reduced. However, the cyclic imides did not accelerate HMG-CoA reductase activity, the regulatory enzyme for cholesterol synthesis, in a manner which would accelerate biliary cholesterol excretion. There was no evidence of hepatic cell damage afforded by the drugs based on clinical chemistry values which would induce alterations in bile acid concentrations after treatment of the rat. PMID- 8474959 TI - Anti-ulcer activity of carbenoxolone and ISF 3401 on PGE2 release in rat gastric mucosa. AB - We have investigated the ability of carbenoxolone and ISF 3041, a new carbenoxolone derivative, to protect the rat gastric and intestinal mucosa against lesions induced by acetylsalicyclic acid (ASA) and indomethacin. Moreover, we determined the capacity of the rat gastric mucosa to release PGE2 both in vitro and ex vivo, in the presence or absence of carbenoxolone or its analogs. These compounds are effective against lesions induced by ASA and intestinal damage induced by indomethacin. The amount of PGE2 obtained from incubated rat gastric mucosal pieces by in vitro and ex vivo indicate that carbenoxolone and ISF 3401 cause a concentration related increase of PGE2 with exception of the highest concentration. Increased prostaglandin content of gastric mucosa can partly explain the gastric and intestinal protection of these compounds and additional mechanisms could be involved in this action. PMID- 8474960 TI - The inhibition of platelet aggregation by activated macrophages is blocked by dexamethasone. AB - The effect of dexamethasone on the ability of activated J774 macrophages to inhibit platelet aggregation was investigated. After 24h incubation with lipopolysaccharide and gamma-interferon, J774 cells generated large amounts of nitric oxide and inhibited platelet aggregation. Incubation of the cells with dexamethasone (0.01-10 microM) caused a concentration-dependent inhibition of both the NO2- production and the anti-aggregating activity of the cells. The inhibitory effect of dexamethasone was blocked by the glucocorticoid antagonist RU 38486. These data suggested that the protective effect of glucocorticoids in endotoxin-induced hypotension and their immunosuppressive action may both depend, at least in part, on the inhibition by these steroids of the induction of the nitric oxide synthase. PMID- 8474961 TI - Effects of drugs used in the therapy of detrusor hyperactivity on the volume induced contractions of the rat urinary bladder. AB - In this study we examined the effects of the drugs most commonly utilized in the therapy of overactive detrusor, on the volume-induced contractions of rat urinary bladder. Anticholinergics such as propantheline bromide and emepronium bromide, as well as oxybutynin decreased the amplitude of the voiding contractions after intravenous (i.v.) administration in a dose-dependent way. These anticholinergics, on the other hand, generally increased the frequency of the contractions. Nifedipine dose-dependently reduced the amplitude of the contractions. Flavoxate induced a dose-related decrease in the frequency without effects on the amplitude of the peaks. Its main metabolite 3-methylflavone-8 carboxylic acid (MFCA) was inactive after i.v. administration. Terodiline was active on the amplitude and apparently on the frequency of the voiding contractions. The alpha-adrenoceptor antagonist prazosin, as well as indomethacin, inhibited only the frequency of the voiding contractions. All the drugs active in reducing the frequency of the voiding contractions after i.v. administration, proved effective also after intracerebroventricular (i.c.v.) injection. The model of the volume-induced contractions of rat urinary bladder, seems to be a useful tool to evaluate in vivo the effects of a compound on the bladder, allowing the possibility of distinguishing among antimuscarinics and calcium antagonists, which peripherally decrease bladder contractility, and other drugs inducing a decrease in the frequency of the voiding reflex acting on the micturition centre(s) in the central nervous system (CNS). PMID- 8474962 TI - Picroliv protects against aflatoxin B1 acute hepatotoxicity in rats. AB - The hepatoprotective activity of Picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, has been investigated by studying the protection of biochemical and histological changes induced in livers of rats given single oral doses (7 mg/kg) of aflatoxin B1. Administration of aflatoxin B1 resulted in a significant increase in 5'-nucleotidase, r-glutamyl transpeptidase, acid ribonuclease, total lipids, cholesterol and lipid peroxides in liver and transaminases, alkaline phosphatase and bilirubin in serum. However, the activity of glucose 6-phosphatase and levels of cytochrome P450, cytochrome b5, DNA, RNA, proteins and glycogen in liver and total proteins in serum decreased. The liver histology showed ballooned hepatocytes, degeneration, microvesicular fat, focal necrosis, bile duct hyperplasia and proliferation of oval and spindle cells in portal tracts. When Picroliv (25 mg/kg x 7 days) was given to aflatoxin B1 toxicated rats, the majority of the biochemical and histological changes were significantly protected. The findings indicate a hepatoprotective activity of Picroliv against aflatoxin B1 toxicity in rats. PMID- 8474963 TI - Temazepam: pharmacological profile of a benzodiazepine and new trends in its clinical application. PMID- 8474964 TI - Polymorphism of debrisoquine and mephenytoin hydroxylation among Estonians. AB - Debrisoquine and S-mephenytoin hydroxylation polymorphisms were studied in 156 unrelated native Estonians. The hydroxylation phenotypes were assessed by coadministration of mephenytoin with debrisoquine or dextromethorphan. The frequency of the poor metaboliser phenotype of debrisoquine/dextromethorphan was 4.5% (95% confidence interval 1.2-7.8%), and that of mephenytoin was 3.9% (95% confidence interval 0.9-6.9%) among Estonians, which is very similar to what has been reported in other Caucasian populations. PMID- 8474965 TI - Toxicity of vitamin D analogues in rats fed diets with standard or low calcium contents. AB - Sprague-Dawley rats were fed either a standard diet with 0.9/0.7% Ca/P or a semisynthetic low-calcium diet with 0.5/0.4% Ca/P and treated orally for 28 days with 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3], a synthetic analogue of the physiologically active form of vitamin D3, 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], at dose levels of 0.2 and 2.0 micrograms kg/day. The high dose caused severe hypercalcaemia with retarded growth, nephrosis, and structural bone changes in rats fed the standard diet. The same dose caused only slight hypercalcaemia without growth retardation or bone changes, and only minimally affected the kidneys in rats fed the low-calcium diet. Hypercalcaemia with less pronounced pathological changes was found in the standard diet low-dose rats, whereas no hypercalcemia or pathological changes were found in the low-calcium diet low-dose group. The rats fed the low-calcium diet tolerated 1 alpha(OH)D3 at dose levels up to 10 times higher than rats on the standard diet. The use of diets low in calcium and low in phosphorus will thus allow the administration of higher dosages of vitamin D compounds without causing hypercalcaemia. This may permit a better evaluation of the pharmacologic and toxic effects not directly associated with the calcium-regulating properties of vitamin D metabolites and analogues. PMID- 8474966 TI - Tolerance to hexobarbital induced by short-term treatments with diazepam and tested with an EEG-threshold test in male rats. AB - Male Mol: SPRD rats were treated with 5 or 20 mg/kg of diazepam for 4 days. The treatment was repeated at two different ages. Diazepam was either dissolved in Intralipid (KABI, Sweden) or dispersed in gummi arabicum. Tolerance induced by the treatment was tested with an EEG-threshold technique where hexobarbital was infused intravenously on day 1, 4, 7 and 14 of the abstinence. The threshold was the dose of hexobarbital needed to induce a burst suppression of 1 sec. or more (silent second). After the first diazepam treatment significant increase in the hexobarbital threshold doses were recorded in all but one of the diazepam treated groups. The pattern varied depending on dose, age and solvent. After the second treatment tolerance was seen only when diazepam had been dissolved in Intralipid. Short term treatment with diazepam can induce cross-tolerance to hexobarbital which probably is due to an increased excitation (physical dependence) in abstinence after treatment with diazepam. PMID- 8474967 TI - Defective neutrophil function in workers occupationally exposed to lead. AB - Chemotaxis and nitroblue tetrazolium reduction were measured in peripheral blood neutrophils of workers occupationally exposed to lead. These two neutrophil functions were significantly reduced, as compared to controls, even in those workers with blood lead levels and urinary delta-aminolevulinic acid (ALA-U) concentrations below the currently accepted biological limit values of 60 micrograms/dl and 6 mg/l, respectively. The immunosuppressive effects of relatively low level lead absorption suggests that immune dysfunction may be a sensitive indicator of lead exposure. PMID- 8474968 TI - Metabolism of prednisone in kidney transplanted patients with necrosis of the femoral head. AB - Interindividual variation of the metabolism of prednisolone and of the susceptibility to glucocorticoids might be possible factors contributing to the development of osteonecrosis after renal allotransplantation. As this aspect has not been properly investigated previously, we compared, in the present study, the metabolism of total and free prednisolone in 6 renal allotransplanted patients who subsequently developed osteonecrosis of the femoral head and the metabolism of 6 matched controls, who did not develop osteonecrosis. There was no difference in age, bodyweight, total serum protein or albumin, or in liver or renal function. The baseline cortisol was 54 +/- 23 micrograms in patients with necrosis, and 102 +/- 53 micrograms/l in patients without necrosis (n.s.). Likewise there was no difference in the peak concentration of prednisolone (420 +/- 43 vs. 394 +/- 42 micrograms/l, n.s.), the bioavailability (0.57 +/- 0.09 vs. 0.61 +/- 0.05, n.s.) or in the apparent volume of distribution at steady state (Vdss, 0.37 +/- 0.09 vs. 0.37 +/- 0.04 l/kg, n.s.). The clearance of prednisolone in patients with osteonecrosis was 33% lower (0.79 +/- 0.11 vs. 1.18 +/- 0.13 ml/min./kg b.wt., P < 0.05) and t1/2 was correspondingly 33% longer (246 +/- 18 min. vs. 184 +/- 15 min., P < 0.05) than in patients without osteonecrosis. However, there was no difference in the apparent volume of distribution of free prednisolone (2.07 +/- 0.36 vs. 1.69 +/- 0.28 l/kg, n.s.), in the t1/2 (152 +/- 30 vs. 107 +/- 20 min., n.s.), or in the clearance (7.33 +/- 2.12 vs. 7.82 +/- 1.18 ml/min./kg) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474969 TI - 2-Naphthol metabolism and metabolite transport in the isolated guinea pig mucosa: further evidence for compartmentation of intestinal drug metabolism. AB - As an extension of a previous study on the metabolism of 14C-1-naphthol (1-N) by the isolated guinea pig mucosa (Sund & Lauterbach 1986), the isomeric compound 2 naphthol (2-N, 50-130 nmol/ml) has now been examined. 14C-Labelled drug was added to the luminal or contraluminal fluid bathing the two sides of jejunal or colonic mucosal sheets in a symmetrical set up. After aerobic incubation for 45 min. at 37 degrees, the fluid compartments and the tissue were analysed for parent drug and metabolites. Like 1-N 2-N was transformed into its sulphate and glucuronide. In the jejunum, 2-N was more extensively sulphated than 1-N, whereas in the colon the metabolite profiles (sulphate:glucuronide ratio) of the two isomers were similar. Generally, the metabolism rate of 2-N, its metabolite profile and metabolite transport pattern (lumen: blood distribution ratio) as well as the tissue accumulation of parent drug and metabolites, depended on the side of drug administration and on the tissue studied. Thus, changing the drug administration had a pronounced impact on the jejunal metabolism and transport, but caused only minor effects in the colon. In summary, this study emphasizes that drug metabolism and metabolite transport differ in the small and large intestine. The data further support the hypothesis that jejunal drug metabolism takes place in two compartments, of which the most active one is accessible from the lumen side and the other from the blood side. The possibility that colonic drug metabolism may also involve compartmentation should be considered although the present study provided very little evidence for this. PMID- 8474970 TI - Increase in antioxidant activity in procainamide-treated rats. AB - Recent studies suggest that in vivo procainamide oxidation underlies induction of autoimmunity by this drug. Since drug metabolism may be accompanied by generation of reactive oxygen species, plasma and liver thiobarbituric acid reacting substances (TBARS), activity of erythrocyte and liver superoxide dismutase, catalase, selenium-dependent glutathione peroxidase (Se-GPX), and plasma antioxidant activity in procainamide treated rats were evaluated. Procainamide administration increased liver lipid peroxide levels, intensified the activity of liver catalase and erythrocyte superoxide dismutase, as well as plasma antioxidant activity. The remaining biochemical parameters in the treated rats were within control values, except for the decreased erythrocyte catalase activity. We conclude, that the increased activity of free radicals observed in the treated rats could contribute to the development of procainamide induced side effects. PMID- 8474971 TI - Recirculating, retrograde heart perfusion according to the Langendorff method for evaluation of MTG--methyl-2-tetradecylglycidate, McNeil 3716--cardiomyopathy. AB - Recirculating, retrograde heart perfusion according to the Langendorff method was used in an attempt to further elucidate the cardiotoxicity of methyl-2 tetradecylglycidate (McNeil 3716, MTG) and the eccentric hypertrophy elicited by the compound. In subchronic experiments female rats were exposed to MTG 2 x 10 mg/kg and 2 x 25 mg/kg per day for 4 weeks. At various times hearts were perfused ex vivo for up to 2 hr with either 5 mmolar glucose or 0.5 mmolar palmitate as substrate. Substrate uptake (glucose or palmitate) and enzyme release (LDH-lactic dehydrogenase or CPK-creatine-phosphate kinase) were assessed during perfusion. Biochemical analysis (ATP, ADP, AMP, c-AMP, CP, creatine, pyruvate, lactate, glucose-6-phosphate, glycogen, phospholipids, triglycerides and non-esterified fatty acids) were done in hearts before (drug effect) and after perfusion (stress of perfusion). Besides changes in energy metabolism and high-energy phosphate production, as observed in previous experiments (Bachmann et al. 1984) massive changes were seen in energy reserves in heart tissue (ATP, CP, glycogen, phospholipids and triglycerides). As expected, MTG led to significant increases also in non-esterified fatty acids content in hearts. PMID- 8474972 TI - The relative importance of mutagens and carcinogens in the diet. AB - Known mutagens and carcinogens in the diet were compiled and the risk of cancer was estimated on the basis of average exposure levels in Switzerland and carcinogenic potencies from rodent bioassays. The analysis showed that, except for alcohol, the sum of all known dietary carcinogens could only explain a few percent of the cancer deaths attributed by epidemiologists to dietary factors. The discrepancy was explained by a "carcinogenicity" of excess macronutrients. This hypothesis was based on an evaluation of dietary restriction experiments in rats and mice, where a dramatic reducing effect on spontaneous tumour formation was seen. From these experiments, a "carcinogenic potency" was deduced for food in excess (TD50 approximately 16 g/kg per day). Overnutrition in Switzerland was converted into excess food intake and the cancer risk estimated on the basis of the TD50 value. The resulting risk of 60,000 cases per one million lives would allow to explain by overnutrition almost all "diet-related" cancer deaths in humans. PMID- 8474973 TI - Carcinogenicity and drinking water. AB - Water is a powerful solvent that readily dissolves many natural and synthetic substances from the environment (e.g. inorganic salts, humic acids and pesticide residues). The processes of purification, disinfection and preparation and storage necessary to provide and distribute drinking water may introduce further chemicals, including some used for these purposes and others derived by interaction between them and the compounds of natural origin. The composition of drinking water, therefore, is complex and varies between sites and with the seasons. Modern technology is employed to minimise the amounts of many of these substances, but some may persist, including derivatives generated by halogenation and ozonation for disinfection. Some of the substances are genotoxic in the laboratory and a few are proven experimental carcinogens--all at much higher concentrations than those normally found in a drinking water supply. Many ecological and epidemiological surveys have been done to compare the occurrence of various types of tumour in man with exposure to different types of drinking, but no consistent or reliable association has been found. There are serious and probably irremediable methodological weaknesses in these attempts, because of the difficulty of defining the nature of the waters consumed over a major part of life, and the variable composition of waters. The surveys do not permit even a realistic assessment of the upper confidence limit of the exclusion of the risk. Thus, although there is some experimental indication of the possible presence of carcinogenic substances in most or all drinking waters, and of how they are formed, the concentrations are very low and there is no realistic evidence that they have caused harm to man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474974 TI - Cancer-protective factors in fruits and vegetables: biochemical and biological background. AB - Cancer-protective factors are present in several fruits, vegetables and commonly used spices and herbs. They can be divided into several different groups, based on their chemical structure, e.g. polyphenols, thiols, carotenoids and retinoids, carbohydrates, trace metals, terpenes, tocopherols and degradation products of glucosinolates (i.e. isothiocyanates, indoles and dithiothiols) and others. Among each of these groups of compounds are substances, which may exert their cancer protective action by more than one biochemical mechanism. The biochemical processes of carcinogenesis are still not known in detail and probably varies with the cancer disease in question. Accordingly, the description of the biochemical backgrounds for the actions of cancer-protective factors must be based on a simplified model of the process of carcinogenesis. The model used in this presentation is a generalised initiation-promotion-conversion model, in which initiators are thought to be directly or indirectly genotoxic, promoters are visualised as substances capable of inferring a growth advantage on initiated cells and converters are believed to be genotoxic, e.g. mutagens, clastogens, recombinogens or the like. Experimental evidence for the mechanisms of action of cancer-protective agents in fruits and vegetables that protect against initiation include the scavenging effects of polyphenols on activated mutagens and carcinogens, the quenching of singlet oxygen and radicals by carotenoids, the antioxidant effects of many compounds including ascorbic acid and polyphenols, the inhibition of activating enzymes by some flavonols and tannins, the induction of oxidation- and of conjugation (protective) enzymes by indoles, isothiocyanates and dithiothiones, the shielding of sensitive structures by some polyphenols and the stimulation of DNA-repair exerted by sulphur-containing compounds. Mechanisms at the biochemical level in anti-promotion include the antioxidant effects of carotenoids and the membrane stabilizing effects reported with polyphenols, the inhibition of proteases caused by compounds from soybeans, the stimulation of immune responses seen with carotenoids and ascorbic acid and the inhibition of ornithine decarboxylase by polyphenols and carotenoids. A few inhibitors of conversion have been identified experimentally, and it can be argued on a theoretical basis, that many inhibitors of initiation should also be efficient against conversion. The mechanisms of anticarcinogenic substances in fruits and vegetables are discussed in the light of cancer prevention and inhibition. PMID- 8474975 TI - Issues and controversies surrounding qualitative strategies for identifying and forecasting cancer causing agents in the human environment. AB - Certain chemicals, mixtures of chemicals, exposure circumstances, life-styles and personal or cultural habits, occupations, viruses, living conditions, and physical agents have been causally associated with cancers in humans. Most however are not considered potentially carcinogenic, and the proportion of 'agents' eventually identified to cause cancer is projected to be relatively low. Current methods to identify carcinogenic potential of chemicals rely largely on short-term in vitro and in vivo tests, mid- & long-term in vivo assays, molecular mechanisms, epidemiological investigations, and structural-activity-effect relationships. Thus, the scientific and public health communities must continue to utilize available means and concomitantly strive to develop newer methods and tools to more easily, quickly, cheaply, and reliably identify carcinogens in the human milieu. Since adequate human studies are typically absent, the most useful method for identifying potential human carcinogens continues to be long-term carcinogenesis experiments. Agents identified as causing cancers in humans have been shown to cause cancer in animals, and this knowledge, together with similarities in mechanisms of carcinogenesis across species, led to the scientific logic and public health strategy that chemicals shown clearly to be carcinogenic in animals should be considered as being likely and anticipated to present cancer risks to humans. The quest of hazard identification efforts is cancer prevention, largely by reducing or eliminating exposures to chemicals that cause cancer and other diseases. PMID- 8474976 TI - General preventive measures against carcinogenic exposure in the external environment. AB - Different measures are used to prevent unacceptable carcinogenic exposure from different sources in the external environment, be it accumulated carcinogens from previous pollution, exposure related to life-style, and exposure related to living standards and the organization of the community as a whole. A precondition for goal-directed prevention is knowledge of exposures to carcinogens and measures to minimize or substitute carcinogens in products and in emissions. One of the most significant sources of carcinogens in the outdoor air in many Western countries is the traffic, especially diesel-powered vehicles. Necessary preventive measures include restriction of carcinogenic exhaust from the individual vehicle, plans for the community to diminish transportation needs, as well as to changing the usual behaviour of the individual. Unlike exposure to carcinogens in the surrounding air, exposure to accumulated carcinogens in ground water and in soil at polluted sites may be diminished by the pattern of use. International aspects are involved in for instance minimizing the risk of getting skin cancer from sunlight. Besides protecting vulnerable individuals there should be a global preservation of the ozone layer. Lowering the risk of long transported air pollution, like radioactivity from accidents at nuclear power stations, demands international efforts to increase safety measures and information about accidents. PMID- 8474977 TI - On the substitution for carcinogens in the working environment. AB - The ultimate solution in prevention of occupational cancer risks would be to remove carcinogens from the working environment. Elimination of carcinogenic substances can be achieved by replacement of the carcinogen with non carcinogen(s) having the same functionality, or by using a different process that produces adequate results without the use of carcinogenic agents. This paper presents selected methods and tools, which have been used for substitution purposes in practice. These are: 1. a strategy for substitution, 2. a tool for creating ideas on how to substitute, 3. a software package, SUBTEC, for solving some technical and industrial hygiene problems, and 4. a proposal for a strategy to deal with organizational and psychological barriers encountered when changes are to be introduced. PMID- 8474978 TI - Dietary guidelines and food recommendations in Denmark. Nordic Committee of Foods, Nordic Council of Ministers, National Research Council, Denmark. AB - In Denmark the official dietary guidelines and food recommendations are expressed in the Five Dietary advices and the Danish food circle. Such guidelines are entirely different from recommendations on nutrient intakes, which are expressed in terms of exact values and established through a more formal procedure. Some of the most fundamental principles for food recommendations given to the public are that they are perceived as consistent and based on a firm consensus, and that their relevance and translation into practical action is obvious to the public. When the situation in Denmark is compared to these principles the main issue turns out to be neither lack of consistency in recommendations issued by government agencies and voluntary health organisations, nor is it lack of consensus among the experts about the fundamental messages of the guidelines. A more important problem is that the public does not distinguish between formal recommendations from authorized sources, and a variety of advices from other sources as well as non-formal comments from individual scientists. A cause of serious concern is the fact that the Danish public seems to lack a realistic picture of what the dietary guidelines imply in terms of foods. A number of contradictions is built into the process of communicating dietary recommendations effectively to the public. These can only be solved if the process is planned on a long-term basis. PMID- 8474979 TI - Some ethical considerations and the status of dietary advice. AB - Dietary guide-lines are currently given to whole populations whether the recipients have asked for it or not, and this raises ethical and practical problems. If we have not been asked for advice, what right do we have to tell people what they "ought" to eat? Are we sufficiently sure of the benefits of following our advice? Could we, in fact, be wrong about it? Are we sure of the absence of "side effects" of our advice? If not, are we sure that the balance between risk and benefit is favourable? Might our advice, in fact, do more harm than good? Would it not be better to restrict our advice to those at high risk of diet- related cancer? These issues are all discussed. Furthermore, the conclusions from the European Cancer Prevention (ECP) symposium and workshop on public education on diet and cancer are presented. The major conclusion is that the concept of general guide-lines should be abandoned in favour of guide-lines targeted to specific groups. In addition, it is concluded that the recent evidence had led to considerable confusion regarding dietary fibre and cancer, and also regarding dietary fat and cancer. The recent evidence strengthens the association between high intake of fresh fruit and vegetables and low risk of cancers at a number of sites. PMID- 8474980 TI - Legislation by the European Community on carcinogens. AB - A brief overview is given of the legislation in the European Community concerning the classification and labelling, marketing and use, occupational exposure, etc. of carcinogenic agents. This includes data on the regulation of 739 agents which have been evaluated for carcinogenicity by the International Agency for Research on Cancer and/or the European Community. These data have been collected in a computerized data base. Although no comprehensive evaluation of the legislation is attempted, it is suggested that a number of carcinogenic agents still need attention, and that the labelling requirements should be supplemented with more restrictive legislation. PMID- 8474981 TI - Regulating carcinogenic risks from foodstuffs: present Danish approaches. AB - The aim of the present Danish regulatory toxicological efforts is to identify and eliminate human carcinogens introduced in the human food supply directly or indirectly through the activity of man. The efforts are directed towards food additives, contaminants and food itself, both individual food items and dietary habits. The overall goal is to bring down the incidence of cancer. The scientific rationale for achieving this goal is discussed based upon recent knowledge. It is suggested that more scientific efforts should be directed towards determining the qualitative and quantitative role of the natural food constituents in human cancer causation. PMID- 8474982 TI - Report from the working group on cancer and the non-occupational environment. PMID- 8474983 TI - Report from the working group on occupational cancer. PMID- 8474984 TI - Report from the working group on diet and cancer. PMID- 8474985 TI - Mechanistic modelling and risk assessment. AB - Risk Assessment in the United States has been rapidly changing over the last few years. The historical methods and endpoints by which risk estimates were derived are gradually being replaced by newer methods and a broader spectrum of endpoints. For carcinogenic risk assessment, there is movement from the routinely used "linearized multistage model" for low dose risk estimation to methodology which is more deeply rooted in carcinogenic mechanisms and which allows the incorporation of additional data into the estimation of risks in a direct, quantitative fashion. There is also a determined effort under way to develop methods for assessing risks from exposure based on other endpoints such as effects on the immune system and the reproductive system. This paper briefly discusses some of the statistical and mathematical issues which will play important roles in determining the utility and precision of these new methods for estimating risks from environmental exposures. PMID- 8474986 TI - The concept of multifactorial etiology of cancer. AB - The concept of causes is not just for professional philosophers to discuss. The epidemiologists also have to clarify how the concept is used since its meaning has profound implications for understanding basic measures of exposure-disease association. The concept of cause also has importance when designing a study or when analyzing epidemiological data. The paper describes the components cause model and its relationship with the mechanism of disease action. A measure of interaction is also presented which is based upon the components cause model. The common sense concept of causes also plays a fundamental role for the success of a health preventive programme according to the Health Belief Model. The component cause model may clarify causal patterns in situations when only a few of the exposed get the disease which the programme tends to prevent. PMID- 8474987 TI - Occurrence of carcinogens in the external environment: epidemiological investigations. AB - The variation in cancer incidence between European populations indicates that at least 50% of the cancer incidence in Denmark may be attributable to environmental factors, including factors related to living conditions and lifestyle, and, hence, in principle are avoidable. Based on data from epidemiological studies of cancer causes, it is estimated that 30-40% of the total cancer burden in Denmark could be prevented by application of already available knowledge. Epidemiological studies of cancer occurrence in relation to arsenic in drinking-water, chlorination of drinking-water, nitrates in drinking-water and ambient air pollution are briefly reviewed. Although the causal associations between these factors and cancer in humans are hypothetical and unproven, the available data allow a rough calculation of the maximum proportion of cancer cases which possibly can be caused by these factors. At most, a few percent of the total cancer incidence is attributable to these external environmental factors. PMID- 8474988 TI - Cancer etiology: agents causally associated with human cancer. AB - Cancer is a multifactorial and multistage process, the exact mechanisms of which are still only partially known. However, even in the absence of a complete understanding of the process of carcinogenesis, we have been able to identify several factors which modify the risk of tumour development in humans. These include both endogenous and environmental factors, ranging from exposure to a single identified chemical to the occupations we follow in order to make our living. Cancer prevention strategies may differ in different parts of the world. In Europe, lung cancer is responsible for about one fourth of all cancer deaths and most of it could be prevented by eliminating tobacco smoking. Other exposures that can be controlled include occupational exposures to agents known to cause cancer at sites such as lung, bladder, paranasal sinuses, leukaemia, lymphoma and liver, as well as exposure to sunlight, known to be associated with both non melanocytic and melanocytic skin cancer. Liver cancer is a common cancer in other regions of the world where hepatitis B virus (HBV) infection is endemic; in these areas, fungal contamination of food is also common. While immunization against HBV may be the method of choice in the long run, reduction of exposure to aflatoxins might be a more useful intermediate goal in primary prevention because of the strong interaction between hepatitis B and aflatoxin exposure on liver cancer risk. To date, few chemical agents have been proved to be of etiological relevance to cancer in humans at sites such as the breast (with the exception of oestrogenic hormones), ovary, colon-rectum and prostate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8474989 TI - Chemical carcinogens in the environment: risk assessment for the environment. AB - The high priority of chemical carcinogens in environmental monitoring programmes is primarily due to a fear of a human exposure to these chemicals. Diseases like cancer are, however, also observed in indigenous populations of e.g. fish and shellfish, although these effects in general are rare events in the environment. High levels of carcinogens seem to be required for an influence on the prevalence of cancer, and an influence has almost exclusively been detected on the prevalence of liver tumours in populations of bottom-dwelling fish. The most important ecological aspect of chemical carcinogens in the environment may be the genotoxic potential of the carcinogens. Induced mutations may result in effects on survival or growth of the exposed organisms. In germ cells induced mutations are transmitted to future generations, resulting in an anthropogenic increase in the background mutation rate. The structure and function of the ecosystem is in the long run somehow determined by the background mutation rate which raises the question whether an increase in the mutation rate is advantageous or disadvantageous from a population and evolutionary point of view. To date experimental knowledge is hardly available even on the type of changes to be expected. PMID- 8474990 TI - Risk assessment for people exposed from different environments. AB - After the identification of the hazardous intrinsic properties of a carcinogen an attempt is made to estimate, if possible, the potency of the carcinogenic effect. For the evaluation it is, furthermore, of interest to know the genotoxic properties of the chemical. The next step would be to try to estimate the potential exposure for people in different environments. This could be intake from use of it as an additive in food or occurrence as a contaminant in food, drinking water, soil or air. The air exposure might come from contaminants in the working environment, in-door air or ambient air. The outcome of the hazard and exposure assessments would not be the only factors in a risk assessment or suggested limit values. Other factors might be the political-administrative background coming from different legal systems, even in the same country, which might apply different safety ambitions. This might result in the application of different risk levels (1:1 million, 1:10 million) or different safety factors, if that approach is used for non-genotoxic animal carcinogens. PMID- 8474991 TI - Airborne carcinogens. AB - Air pollution has been recognized as a cancer risk for many years. More than 2,800 different chemicals have been identified in the air or emission sources. Only about 10% of these chemicals have been evaluated in bioassays for genetic or carcinogenic effects. Hydrocarbons, nitrogen-containing organics, and halogenated organics account for nearly 60% of the airborne chemicals that have been studied in long term animal cancer bioassays or short-term genetic bioassays. The sources that emit the highest number of these potentially carcinogenic chemicals are sources involving combustion (e.g., tobacco smoke, automobile exhaust, and coal combustion). Quantitative estimates of the risk of airborne carcinogens in outdoor air consistently show that polycyclic organic matter (POM) from products of incomplete combustion (PICs) make the largest single contribution to human cancer risk. Although the POM emissions from various air pollution sources are chemically similar and induce cancer by a similar genotoxic mechanism, the cancer risk per unit of exposure of these emissions may vary by several orders of magnitude. Among these combustion sources motor vehicle emissions account for the greatest cancer risk in outdoor air. Environmental tobacco smoke (ETS) and radon are the major sources of cancer risk from indoor exposures. There are, however, many uncertainties in identifying the important airborne carcinogens and quantitating the human cancer risk of air pollution. One important uncertainty is the role of atmospheric transformation products in human cancer. PMID- 8474992 TI - Cancer and ionizing radiation. AB - The carcinogenic effects of ionizing radiation are well documented at high doses and high dose rates. The Danish population has always been exposed to ionizing radiation from natural sources. In this century exposures from man-made sources especially in the medical field have added to the overall exposure of the population. Excluding medical exposures and exposures in the working environment the exposures of an individual member of the Danish population are essentially coming from natural sources especially from radon in dwellings. On average these sources give an annual effective dose equivalent of 3 mSv. A risk assessment using the latest information on the carcinogenic effects of ionizing radiation indicate that these radiation sources could give rise to 300 lung cancer deaths (radon) and 250 fatal cancers (other sources) each year in Denmark. PMID- 8474993 TI - Cancer and UV-radiation. AB - Solar radiation is a well documented risk factor in melanoma and non melanocytic skin cancer (i.e. basal cell and squamous cell carcinoma). It has been suspected to play a role also for lip cancer and for eye melanoma. Primary prevention should include advises to the public about sensible sun exposure. Results of such efforts will be apparent only in a long term perspective. PMID- 8474994 TI - Carcinogenic chemicals in the occupational environment. AB - A survey of occupational carcinogens by the Institute of Occupational Health, Finland shows that more than 100,000 workers are exposed to carcinogenic substances. The most common exposures are silica, wood dust, tobacco smoke and lead compounds. Based on biological monitoring of workers over the years it appears that overall lead exposure has decreased but exposure to styrene, trichloroethylene and tetrachloroethylene has decreased only slightly or remained constant. The biological monitoring data are based on samples sent by the workplaces on their initiative presenting no scientifically selected sampling. Thus due caution is needed in the interpretation of the trends. PMID- 8474995 TI - Availability of data on humans potentially exposed to suspected carcinogens in the Danish working environment. AB - For the majority of suspected carcinogens only little or no human evidence exists, and in general on-going epidemiologic studies fail to address this fast growing group of chemicals. A survey based on a Danish occupational surveillance system concerning data on present and historical import, production and use of the 167 chemicals evaluated by the International Agency for Research on Cancer as possible or probable carcinogens, shows that about 110 of these chemicals are on the market in Denmark at present. Only 32 are used in industry in relatively large quantities. For some of these chemicals it is possible to identify clusters of companies, including historical cohorts of potentially exposed workers. Measurements of airborne pollutants are available for some few of the suspected carcinogens, indicating decreasing time trends and various levels in different industries. In spite of some limitations, this information on potential exposure has on ad hoc basis been linked to an existing cancer registry based occupational surveillance system, and various studies based on the total body of data are on going, as a preliminary approach to give at least some human evidence to some widespread animal carcinogens. PMID- 8474996 TI - Human biological monitoring of occupational genotoxic exposures. AB - Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e.g. the quantitation of identified DNA-adducts or substance unspecific as is the measurement of DNA repair. The sample material used for analysis must be well characterized and subject to uniform processing for comparison of the results. Confounding factors of smoking, age and sex must be well controlled for and the biomonitoring results should preferentially be linked with accurate ambient air monitoring. In persons occupationally exposed to styrene the endpoints of DNA-damage and DNA-repair in genetic monitoring are methods of choice in exposure situations above the current Danish (25 ppm) or Finnish (20 ppm) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors and confidentiality as well as ownership of the results. PMID- 8474997 TI - Cancer risk related to genetic polymorphisms in carcinogen metabolism and DNA repair. AB - Chemical carcinogenesis involves metabolism in the body of the carcinogen to the ultimate carcinogen and its interaction with DNA. There is considerable interindividual variation in the metabolic ability to activate as well as detoxify the carcinogens and in the ability to repair the carcinogen-DNA adducts. In many cases such differences occur as genetic polymorphisms and form the basis for variation in susceptibility to carcinogens and thereby to cancer risk. The activation mechanism is particularly related to the cytochromes P-450 (CYPs), and four of these are known to activate carcinogens: CYP1A1, CYP1A2, CYP2E1, and CYP3A4. Increased cancer risk has been related to polymorphisms in the CYPs and other activating enzymes. The DNA repair mechanisms show considerable complexity, and deficient repair mechanisms in certain human disorders are clearly related to increased cancer risk. Yet, there is no unambiguous epidemiological evidence available for cancer risk among individuals in general. In vivo methods have to be refined and developed for use in epidemiological studies. PMID- 8474998 TI - Biological evaluation of protein quality of sorghum as affected by insect infestation. AB - Protein quality of sorghum grains having 25, 50 and 75% infestation caused by mixed population of Trogoderma granarium Everts and Rhizopertha dominica Fabricius was biologically evaluated by rat growth and nitrogen balance studies. Feeding of diet containing insect infested sorghum grains (50 and 75%) resulted in marked decrease in food intake, protein intake, gain in body weight, food efficiency ratio, protein efficiency ratio, nitrogen consumption, nitrogen absorption, biological value, net protein utilization, dry matter digestibility, net protein retention and protein retention efficiency. These parameters showed negative association with insect infestation levels. However, 25% level of grain infestation did not affect these parameters significantly. PMID- 8474999 TI - Studies on some edible wild mushrooms from Nigeria: 1. Nutritional, teratogenic and toxic considerations. AB - The biological value of 5 mushrooms Chlorophyllum molybditis, Psathyrella atroumbonata, Termitomyces robustus, Termitomyces striatus and Volvariella esculenta from our collection of wild edible mushrooms were determined using weanling rats. C. molybditis supported rapid growth with PER (2.63) higher than the casein control (2.50). P. atroumbonata was average in biological performance (PER 1.50) while T. robustus and V. esculenta did not support growth at all. Rats on T. striatus dried at 60 degrees C for 48 h lost weight rapidly and showed pathological signs of toxicity by the second day. All rats on this diet died by the fourth day of the experiment. When the diet of T. striatus dried at 90 degrees C for about 8 h was fed, the rats gained weight marginally but all survived. Prolonged storage of T. striatus at 60 degrees C for 5-8 weeks also seemed to detoxify the poisonous component such that PER and NPR values were 0.8 and 2.0 respectively. 2 pairs each of adult rats fed C. molybditis and Tricholoma lobayensis diets for 10 days were mated. Rats of C. molybditis diet gave 5 and 6 litters each and only one of these litters seemed to have retarded growth. Rats on T. lobayensis diet did not produce any litters for 14 weeks but the female produced off-spring when mated with control male rats. PMID- 8475000 TI - Protein quality evaluation of amaranth in adult humans. AB - This study was carried out to determine the nutritional quality of the protein of amaranth grain submitted to extrusion and popping processes, using cheese protein as reference. For the biological evaluation, the short-term nitrogen balance index method was followed with 12 experimental adult male human subjects. A Latin square series 3 x 3 was used (three periods, three subjects) as an experimental design balanced to minimize residual effects by randomly ordering treatments, columns and rows. The study consisted of three periods of nine days each. The first period started by feeding all subjects a low nitrogen diet, followed by increases of the protein level every two days. The levels were 0.2, 0.4, 0.6/g protein/kg/day, keeping other nutritional elements constant and adequate, including calories, minerals and vitamins. All subjects received all their meals using as a source of protein extruded amaranth, popped amaranth or processed cheese. Water intake was kept at a rate of 0.8-1.0 ml per calories consumed. During the study, the subjects maintained regular physical activity. Amaranthus cruentus was utilized. The extruded amaranth was prepared with the Brady Crop Cooker under conditions previously established in other studies. The popped amaranth was prepared at a 250 degrees C temperature during 15-20 sec. The extruded and popped amaranths were provided as a sweet puree and, as all the other foods conforming the diets of each subject, they were weighed with 0.1 g of accuracy. Diet samples, as well as faeces and urine, were collected daily, which were ordered according to period and level of protein, conforming pools to determine their nitrogen content by the Kjeldahl method. True digestibility results of the protein were 101.4, 89.8 and 85.5% for cheese, extruded amaranth and popped amaranth, respectively. The statistical analysis according to the Tukey test showed that the true digestibility of the protein was the same for the two products of amaranth and different than the digestibility of cheese. Nitrogen balance index values from the equation between nitrogen intake and nitrogen retained, were 0.97, 0.86 and 0.79 for cheese, extruded amaranth and popped amaranth, respectively. The respective values between nitrogen absorbed and nitrogen retained were 0.97, 0.98 and 0.96. The Tukey test indicated that for NI to NR cheese was statistically different for the two amaranth products, which were similar between them. For the relationship NA to NR all values were statistically the same.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475001 TI - Chemical and nutritional evaluation of two amaranth (Amaranthus cruentus)-based infant formulas. AB - The objective of this study was to calculate, prepare and evaluate the Protein Efficiency Ratio (P.E.R.) and Net Protein Utilization (N.P.U.) of two infant formulas made with amaranth (Amaranthus cruentus). Both formulas were formulated to match a previously developed and tested soy-oats infant formula. No significant differences were found between the three formulas with respect to corrected Protein Efficiency Ratio (P.E.R.) and Net Protein Utilization (N.P.U.) values. Only the product made with the 1-R fraction of amaranth was found to have a significantly lower P.E.R. than casein. PMID- 8475002 TI - Effects of dry heat treatments to peanut kernels on the functional properties of the defatted meal. AB - Dry heat treatments at 140 degrees C for 20 min or 160 degrees C for 10 min of peanut kernels significantly improved protein solubility, water and oil absorptions, foaming capacity and stability, and least gelation concentration of the defatted meal. However, heat treatments at 160 degrees C for 30 min or more than 30 min period resulted in significant decrease in these properties. Such heat treatments significantly decreased the level of albumin and globulin fraction with concomitant increase in glutelin fraction in the meal. PMID- 8475003 TI - Protein and lysine digestibility and protein quality of cooked Filipino rice diets and milled rice in growing rats. AB - The protein quality of typical rice-based menu of Filipino preschool child and adult and cooked milled rice was assessed for true digestibility (TD), biological value (BV) and net protein utilization (NPU) in growing rats. Lysine and energy digestibilities were also determined. For the preschool child diet, TD was 88.8%, BV 90.0%, and NPU 79.9%. For the adult diet, TD was 87.3%, BV 86.6%, and NPU 75.5%, whereas cooked rice had 90.0% TD, 82.5% BV and 74.3% NPU. Lysine digestibility was 95.4% for preschool child diet, 95.7% for adult diet, and 100.0% for rice. Digestible energy was 91.3% for preschool child diet, 93.0% for adult diet, and 95.3% in rice. Amino acid scores were 100.0% for preschooler diet, 92.1% for adult diet, and 62.2% for rice. Protein quality based on amino acid score corrected for TD was 88.8% for preschool child diet. 80.4% for adult diet, and 56.0% for rice. If based on lysine digestibility instead of TD, protein quality would be 7.1% higher. PMID- 8475004 TI - Studies on the development of high-protein biscuits from composite flours. AB - Composite flours prepared from wheat, greengram, bengalgram and blackgram flours were studied for the preparation of biscuits. Protein content of biscuits increased as the level of the pulse flours increased. Wheat flour containing bengalgram and blackgram flours adversely affected the top grain, texture and colour of biscuits. Biscuits made with higher levels of bengalgram (more than 15%) were tough and difficult to break and required higher compression force. Addition of greengram flour did not significantly affect top grain, texture and colour of biscuits. The biscuits made from 15% greengram supplemented wheat flour scored the highest for flavour characteristics. Thickness, diameter and spread ratio of biscuits containing different levels of pulse flours were significantly different from control sample. Sensory evaluation scores showed that acceptable biscuits can be prepared from wheat flour supplemented with these pulse flours at a level of 15 percent. PMID- 8475005 TI - Protein, calcium, iron, and amino acid content of selected wild and domesticated cultivars of finger millet. AB - Two wild and eight domesticated cultivars of finger millet were analyzed to determine their proximate composition and calcium, iron, and amino acid content. Wide variations were observed in the protein (mean values ranged from 7.5 to 11.7%), calcium (376 to 515 mg/100 g), and iron (3.7 to 6.8 mg/100 g) content of the wild and domesticated cultivars. A wild progenitor of finger millet, E coracana subsp. africana was significantly higher in protein than four of the six domesticated accessions analyzed. The calcium and iron content of the wild progenitor was also significantly greater than that of two domesticated cultivars. The wild species was also found to be higher in lysine and five other essential amino acids. These results indicate that the nutritional value of finger millet may be significantly improved by selective crossbreeding of the cereal's wild and domesticated cultivars. PMID- 8475006 TI - Breast cancer screening practices among retirement community women. AB - BACKGROUND: The purposes of this study were (a) to learn more about the existing breast cancer screening practices of women age 65 and older and (b) to identify factors related to breast cancer screening. METHOD: A random sample of 752 women age 65 and older residing in independent living apartments in eight retirement communities was selected to participate in a survey of breast cancer screening practices and related factors. A total of 616 surveys were complete, yielding a response rate of 82%; of those, 571 of the surveys were administered by telephone, with the remaining 45 administered in person. RESULTS: Thirty-eight percent of the women reported having had a mammogram within the past year, 53% had a clinical breast exam, and 39% reported performing monthly breast self examination. The percentage of women reporting either annual clinical breast examinations or mammography decreased with increasing age. Results of a logistic regression analysis found that having discussed mammography with a physician, believing in the need for mammography, having no mammography-related concerns, and the combination of personal experience with breast cancer and having had a clinical breast examination in the past year were all independently related to having had a mammogram within the past year (P < 0.05). CONCLUSION: In order to increase older women's participation in screening, particularly in mammography, educational interventions need to be developed and directed both to older women and to their physicians. PMID- 8475007 TI - The effect of physician advice on exercise behavior. AB - BACKGROUND: Although sedentariness, a prevalent lifestyle, is recognized as a significant risk factor for coronary artery disease and other conditions, little is known about the effectiveness of prevention strategies in the primary care setting. This study examines the impact of brief, exercise advice-giving by family physicians. METHODS: During a 2-month baseline period, patients visiting their family physician and who were age 18 or older were queried about their exercise habits and attitudes and whether their physician had discussed exercise. During the following 2-month experimental phase, the same data were gathered, and half the physicians were trained to give brief exercise advice. All patients were followed for 1 month. Changes in exercise duration and frequency were the primary outcome measures. RESULTS: During baseline, a sizable portion of patients were given exercise advice. This was true also of control group patients during the experimental phase, although trained physicians gave advice almost twice as often. A comparison of the patients receiving advice with those not receiving advice revealed significant increases in exercise duration, but not frequency. Patient attitudes were responsive to exercise advice. CONCLUSION: Members of primary care, adult patient population will increase their duration of physical activity in response to physician advice to exercise. PMID- 8475008 TI - Oral contraceptive use and the occurrence of gallstone disease--a case-control study. AB - BACKGROUND: We evaluated the hypothesized transient effect of oral contraceptive use on the occurrence of gallstone disease in a case-control study. METHODS: The study comprised 82 acute cases, and 249 general population controls, 28 elective cases, and 106 radiodiagnosis controls. Risk-period-specific rate ratios were estimated by logistic regression analysis. RESULTS: During the first 5 years after any year of oral contraceptive use (0- to 5-year risk period) the rate ratio was 1.6 (90% confidence interval, 0.83-2.95), and for the 6- to 10- and 11- to 20-year risk periods, 1.2 (0.67-2.13) and 1.1 (0.69-1.65), respectively. Further evaluation showed substantial confounding by other risk factors. After these were controlled for, the rate ratios were 1.1, 1.8, and 1.0 for the respective risk periods. When oral contraceptive use had been started recently (within 5 years before diagnosis) the rate ratio was 4.8 (0.79-29.7); recent oral contraceptive use was not associated with gallstone disease if preceded by 6 or more years of oral contraceptive use (rate ratio 0.8 (0.15-4.55)). CONCLUSIONS: The results are consistent with a transient effect of oral contraceptive use that does not accumulate beyond 10 years of use. However, the substantial confounding effect in our study raises the question whether the present and previously reported estimates of the effect may be biased by confounding. PMID- 8475009 TI - Beneficial effects of sun exposure on cancer mortality. AB - For more than 50 years, there has been documentation in the medical literature suggesting that regular sun exposure is associated with substantial decreases in death rates from certain cancers and a decrease in overall cancer death rates. Recent research suggests that this is a causal relationship that acts through the body's vitamin D metabolic pathways. The studies reviewed here show that (a) sunlight activation is our most effective source of vitamin D; (b) regular sunlight/vitamin D "intake" inhibits growth of breast and colon cancer cells and is associated with substantial decreases in death rates from these cancers; (c) metabolites of vitamin D have induced leukemia and lymphoma cells to differentiate, prolonged survival of leukemic mice, and produced complete and partial clinical responses in lymphoma patients having high vitamin D metabolite receptor levels in tumor tissue; (d) sunlight has a paradoxical relationship with melanoma, in that severe sunburning initiates melanoma whereas long-term regular sun exposure inhibits melanoma; (e) frequent regular sun exposure acts to cause cancers that have a 0.3% death rate with 2,000 U.S. fatalities per year and acts to prevent cancers that have death rates from 20-65% with 138,000 U.S. fatalities per year; (f) there is support in the medical literature to suggest that the 17% increase in breast cancer incidence during the 1991-1992 year may be the result of the past decade of pervasive anti-sun advisories from respected authorities, coinciding with effective sunscreen availability; and (g) trends in the epidemiological literature suggest that approximately 30,000 U.S. cancer deaths yearly would be averted by the widespread public adoption of regular, moderate sunning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475010 TI - Targeting breast and cervical cancer screening to elderly poor black women: who will participate? The Harlem Study Team. AB - BACKGROUND: Factors associated with participation in breast and cervix cancer screening among elderly black women of low socioeconomic status were determined. METHODS: Data from a baseline cross-sectional random survey were used together with data on whether screening was subsequently completed or refused. The subjects were a random sample of women attending an urban public hospital primary care clinic for routine medical care with a birth year of 1924 or earlier. RESULTS: Among the 271 women in the study group, 70% completed screening. Stated intent was the strongest predictor of participation; women who intended to have both mammography and Pap testing were 2.7 times more likely to participate than those who intended to have neither test (95% confidence interval 1.4, 4.9; P < 0.01), controlling for age, insurance status, and level of chronic illness. Women who had more than three chronic illnesses were twice as likely to participate than those with three or fewer illnesses (95% confidence interval 1.1, 3.4 P < 0.02), controlling for the remaining variables. Other variables, including age, history of a recent screening examination, attitudes, or knowledge, were not related to participation. Stated intent was the only variable that predicted compliance with both mammography and Pap smear completion in separate regression models for the individual tests. CONCLUSION: A high proportion of elderly, socioeconomically disadvantaged black women will participate in cancer screening when it is offered in a primary care setting. Further research on behavioral intentions should be conducted to refine interventions designed to enhance the use of early cancer detection among vulnerable population groups. PMID- 8475011 TI - Impact of a breast cancer screening community intervention. AB - BACKGROUND: Efforts to detect breast cancer in its early stages are necessary to reduce breast cancer-associated mortality. This study evaluated the impact of a multicomponent intervention implemented between 1987 and 1990 to increase a community's utilization of breast cancer screening by women over 50 years of age. METHODS: The study used a pretest/post-test two-community design, with one community assigned as the intervention community and the other as the comparison. The intervention consisted of a comprehensive physician involvement component and a community education effort. To assess the overall impact of the interventions, we measured women's participation in screening via random digit dial telephone surveys at three time points, each approximately 18 months apart. RESULTS: Over the course of the study, there were dramatic improvements in breast cancer screening participation in both communities. However, the intervention city showed more improvement in selected variables than did the comparison community in the early phases of the project between baseline and midpoint. These included increased advice by physicians to have mammograms, increased awareness that screening is necessary in the absence of symptoms, increased awareness that many women over 50 have mammograms, decreased perception of barriers to clinical breast exam, and an increase in the proportion of women having a clinical breast exam. In addition, significantly fewer women in the intervention city than in the comparison city reported never having had a mammogram at midpoint. CONCLUSIONS: The findings demonstrate limited impact of a community intervention during a period of increasing adoption of mammography screening, in part, due to this rapidly rising secular trend. Additionally, increased activities in the comparison community were documented. Therefore, as incidence of screening increases, targeted activities aimed at population subgroups are warranted, and evaluation designs need to include multiple comparison groups or broader geographic random samples. PMID- 8475012 TI - Educational attainment and coronary heart disease risk: the Framingham Offspring Study. AB - BACKGROUND: Efforts to control the continuing epidemic of coronary heart disease in the United States have been successful according to certain criteria, such as mortality, but by others, such as morbidity, the picture is less clear. Documenting whether various subgroups of the population have adopted healthier lifestyles that are likely to reduce coronary heart disease risk is essential to understanding the status of the epidemic and, most importantly, to formulating prevention and health education strategies that will ameliorate its effects. METHODS: The Framingham Offspring Study cohort participated in extensive health screening protocols to determine their cardiovascular risk. The 2,846 men and women who were between the ages of 25 and 64 years and who reported their educational attainment level are the subject of this report. RESULTS: Both body mass index and cigarette smoking showed inverse relationships to educational attainment among both men and women, while reported vigorous leisure time physical activity showed a positive relationship to educational attainment. However, fitness levels as assessed by treadmill duration were directly related to educational attainment only the women. With the exception of total plasma cholesterol among women, all coronary heart disease risk factors had most adverse levels in the least educated study participants. CONCLUSIONS: This study indicates that most components of the coronary heart disease risk profile show adverse levels in individuals with low educational attainment. PMID- 8475013 TI - Knowledge, attitudes, and personal practices regarding prevention and early detection of cancer. AB - METHODS: To determine population knowledge, attitudes, and personal practices regarding prevention and early detection of cancer, random population samples of 25- to 74-year-old men and women in six various-sized communities in three upper midwestern states (N = 4,915) were administered surveys and interviews during 1987-1989. RESULTS: Four-fifths of respondents believed cancer to be preventable. Knowledge of warning signs/symptoms of cancer and of leading causes of cancer, however, was low. Over 95% of women had had a Papanicolaou smear and a clinical breast exam or had performed a breast self-exam; 65.7% of those ages 50-65 years had had a mammogram. Among men and women ages 50-65 years, 77% had had a digital rectal exam; 52.5%, a fecal occult blood test; and 48.3%, a sigmoidoscopy. CONCLUSIONS: Conditions are favorable for an increase in mammography, including favorable attitudes toward cancer prevention, strong consensus among policy making organizations regarding guidelines for obtaining mammograms, and high levels of adherence to these recommendations by women who have had at least their first mammogram. Challenges now include acceptance of these guidelines by physicians, mammogram affordability/availability, and demonstration of efficacious, cost-effective, and reliable colorectal/prostate cancer screening tests. PMID- 8475014 TI - Health practices and disability: some evidence from Alameda County. AB - With greater longevity people are increasingly concerned about how to avoid disability during their longer lives. Policy decisions concerning ways to extend health as well as life have become part of the nation's health agenda. Opportunity to examine that issue has arisen in the Alameda County Human Population Laboratory. Earlier studies there established seven health practices as risk factors for higher mortality: excessive alcohol consumption, smoking cigarettes, being obese, sleeping fewer or more than 7-8 hours, having very little physical activity, eating between meals, and not eating breakfast. Observation now reveals that, taking into account age, gender, physical health status, and social network index in 1965, the occurrence of disability was only about one-half as great among the cohort survivors in 1974 who reported good health practices in 1965 as among those with poor health practices; those with an intermediate level of health practices experienced about two-thirds the relative disability risk of those with poor health practices. Essentially similar relationships prevailed for the 1982/1983 survivors of the original (1965) cohort who, upon requestioning, had been found to be without disability in 1974. PMID- 8475015 TI - Physician-based diet counseling for cholesterol reduction: current practices, determinants, and strategies for improvement. AB - BACKGROUND: Physicians face increasing pressure to counsel their hypercholesterolemic patients about diet. To design effective physician-based treatment programs, a better understanding of current dietary counseling practice and its determinants is needed. METHODS: Using a survey previously tested for reliability and validity, we examined the relationship of dietary knowledge, attitudes, beliefs, organizational barriers, and treatment practices for cholesterol management among 60 resident and attending physicians practicing in the general medicine clinic of a university medical center that serves primarily rural and disadvantaged patients. The survey was administered in October of 1988 prior to the release of the National Cholesterol Education Program Guidelines. RESULTS: The response rate was 100%. Ninety-two percent of physicians surveyed believe that dietary treatment effectively lowers cholesterol and 68% feel responsible for providing such therapy. However, most (72%) feel ill-prepared to give diet counseling, lack confidence in their ability to help patients make meaningful dietary changes (95%), and cite organizational barriers, such as limited time (72%) or inadequate educational materials (47%). Physicians were more likely to report behaviorally focused diet counseling practices if they felt prepared to counsel (r = 0.42, P < 0.001), were confident in their counseling skills (r = 0.39, P < 0.01), or reported personally following a prudent diet (r = 0.36, P < 0.01). We discuss the implications of these findings and how they should guide the design of physician-based dietary interventions for cholesterol reduction. PMID- 8475016 TI - [Heat inactivation kinetics of solubilized and immobilized immunoglobulins G]. AB - The kinetics of thermoinactivation of rabbit antibodies against cortisol (Anti COR, 60-82 degrees), sheep antibodies against rabbit immunoglobulins (AB, 65-77 degrees) in water solution and of AB covalently linked to activated polystyrene beads (PSB-AB, 60-77 degrees) was studied by indirect and direct ELISA methods using peroxidase-cortisol or peroxidase-rabbit immunoglobulin conjugates to detect immunocomplexes for PSB-AB. High stability of ABs and their stabilization after immobilization on PSB are shown. The Eact values and thermodynamic activation parameters of immunoglobulins thermolysis delta H*, delta S* and delta G* were calculated from Arrhenius plots of the effective inactivation rate constants versus temperature and compared with the corresponding characteristics for other proteins. PMID- 8475017 TI - [Biosynthesis of bovine growth hormone in Escherichia coli DH1 cells and its purification on a pilot scale]. AB - The biosynthesis of the bovine growth hormone (BGH) in E. coli DH1 cells containing the plasmid pbGH(1-119)ptrp was studied. It was found that BGH accumulated in the cytoplasm of bacterial cells as optically dense granules that can be isolated by low-speed centrifugation. A fraction of purified protein granules was used for further purification of BGH. A purified BGH preparation contained two polypeptides with molecular weights of 18,000 and 22,000 D. The state of plasmid was investigated during cultivation and storage of the culture. PMID- 8475018 TI - [Characteristics of lipids of microbial origin with regard to triglyceride composition and comparison of them to plant oils]. AB - The triacylglycerol composition of lipids isolated from the yeasts Candida guilliermondii and C. humicola and of food vegetable oils was investigated by HPLC. The triacylglycerol composition of samples was compared using the program "Nearest neighbour" and by plotting images with the help of the software package STATGRAPHICS. The methods used allow us to conclude that microbial lipids are rather promising. PMID- 8475019 TI - [Phase equilibria in water-defatted milk proteins-carboxymethylcellulose sodium salt systems]. AB - Phase equilibria in water mixtures of skimmed milk with sodium salt of carboxymethylcellulose (CMC) was studied using two degrees of CMC polymerization (500 and 200) and substitution (0.8 and 0.5). The increase of the polymerization degree from 200 to 500 resulted in a higher protein yield in the protein phase, while the decrease of the substitution degree from 0.8 to 0.5 caused a noticeable decrease of asymmetry of phase diagrams. The phase separation was accompanied by ion exchange: potassium and calcium ions were mainly found in the protein phase. The highest yield of milk protein into the protein phase was 85% at a CMC concentration of 0.7%. The main protein component of the polysaccharide phase was alpha-lactalbumin. PMID- 8475020 TI - [Fungal tremorogens]. AB - Fungi capable of producing tremorgenic secondary metabolites represent species from taxonomically diverse and unrelated groups. These fungi are capable of contaminating a variety of agricultural commodities such as faragas, corn, silage, etc. Various animal diseases suspected or known to be caused by fungal tremorgens are paspalum staggers, ryegrass staggers, corn staggers, and Bermuda grass tremors. Other syndromes with probable involvement of fungal tremorgens were associated with corn silage contaminated with Aspergillus fumigatus and beer, cream cheese, a hamburger, and walnuts contaminated with Penicillium crustosum. The tremorgens involved in these syndromes (with the exception of the moldy silage) although produced by diversely unrelated fungi, contain the same basis biologically active chemical nucleus derived from geranylgeraniol and tryptophan. In some cases, such as A. flavus and Claviceps paspali, the tremorgens appear to be associated exclusively with the sclerotial stage (ergot). PMID- 8475021 TI - [Ergot alkaloids and alkaloids from other endophytes, responsible for causing toxic syndrome in cattle after eating contaminated grass]. AB - Different signs of ergotism in livestock associated with animals consuming feed grains and pasture grasses infected by Clavicipitaceae (e.g. Balansia spp. and Acremonium spp.) have been considered. Endophyte-infected tall fescue causes the damage to livestock, and its toxicity and ryegrass in livestock are associated with ergopeptide alkaloid ergovaline and indole-isoprenoid lolitrems produced by A. coenophialum and A. lolii. The role of another compound attendant to endophyte infected fescue such as peramine and loline alkaloid is discussed. Concentration of alkaloids depends upon the season and the period of growing plant-host. The advantages and the problems of endophyte-grass mutualistic symbiosis in pasture conditions are considered. The perspective of genetic manipulation of grass and fungus to produce endophyte-infected grasses with stress and insect deterences without affecting ruminant health. PMID- 8475022 TI - [Tremorogenic mycotoxicosis caused by the fungi Aspergillus clavatus, clinical features, pathomorphology, and isolation of metabolites]. AB - Tremorgenic mycotoxicosis of the fungus Aspergillus clavatus growing on malt sprouts under natural and laboratory conditions has been studied. The clinical aspect and pathomorphology of the diseases were investigated and a pure culture A. clavatus was isolated. Three schemes of cultivation of A. clavatus in laboratory conditions were tested to obtain tremorgens. The scheme of cultivation in thermostat at 37 degrees for 7 days and then at 30 degrees C for 10 days and at 22 degrees for 17 days afterwards was found to be optimal. A metabolite close to alkaloids by its physico-chemical characteristics was isolated from the fungus studied. PMID- 8475023 TI - [The effect of elymoclavine and its derivatives on various enzymes of the gastrointestinal tract]. AB - The influence of elymoclavine, elymoclavine hydrochloride, elymoclavine hydrobromide, 2-bromelymoclavine, 2-bromelymoclavine hydrobromide on the initial rater of enzymatic hydrolysis of cytidine-2',3'-monophosphate by RNase A and of N alpha-benzoyl-DL-tyrosine-p-nitroanilide by alpha-chymotrypsin has been investigated. It is shown that all the compounds have the features of various types of inhibitors of RNase A and alpha-chymotrypsin with the exception of elymoclavine which shows all features of a catalytic activator of RNase A. PMID- 8475024 TI - [Propagation of toxigenic fungi and mycotoxins in various grains]. AB - The frequency of occurrence and toxigenicity of various strains of Aspergillus flavus (663 stairs) and of Fusarium spp. (459 strains) isolated from grain of various crops from four grain-producing areas were studied. The analysis of mycotoxins in 1038 grain samples (wheat, rye, rice and corn) and in 58 samples of sun flower seeds collected from commercial batches showed that aflatoxins B1 and G1, deoxynivalenol, and zearalenone are the basic microbial contaminants of grain, while toxin T-2 and diacetoxyscirpenol were found much more rarely. Ochratoxin A, penicillic and kojic acids were found only in several samples. The occurrence of the mycotoxins and contamination levels depended on grain-producing areas. The risk of mycotoxins invasion in grains was greater in southern humid regions of Russia, Kazakhstan and Uzbekistan. PMID- 8475025 TI - [Arthrobacter proteinase and its effect on fibrin thrombi]. AB - Arthrobacteria are producers of proteolytic enzymes. Optimal cultivation conditions were determined for Arthrobacter luteus and the mineral composition of the culture medium providing active synthesis of proteinase was optimized. The proteinase was isolated from the culture liquid of Arthrobacter luteus using preparative ion-exchange chromatography on a carboxyl cation exchange resin KMT. The enzyme was homogeneous according to gel chromatography on Sephadex G-200 and had a molecular weight of 24 kD. The fibrinolytic activity of the proteinase is comparable with that of trypsin. PMID- 8475026 TI - Identification of Schistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro. AB - Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained from S. haematobium-infected patients and sex- and age matched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples form 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84,000, 63,000, 57,000, 55,000, 40,000, 30,000, and 28,000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evoke in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine. PMID- 8475027 TI - Expression of members of the heat-shock protein 70 family in the exoerythrocytic stages of Plasmodium berghei and Plasmodium falciparum. AB - Exoerythrocytic stages of Plasmodium berghei cultured in HepG2-A16 hepatoma cells and those of P. falciparum in human hepatocytes transplanted under the kidney capsule of CB-17/ICr scid/scid mice were used to evaluate expression of heat shock-related stress proteins. Although undetectable in the sporozoites, the expression of proteins similar in sequence of a heat-shock protein of 70 kDa and a glucose-regulated protein of 78 kDa was markedly induced in the hepatic stages of malaria parasites. Expression of these proteins in the exoerythrocytic stages of the malaria parasite warrants a systematic evaluation of their potential role in eliciting cellular immune responses directed against infected hepatocytes. PMID- 8475028 TI - Effect of various digestive enzymes on the interaction of Toxoplasma gondii with macrophages. AB - The participation of resident, elicited, and activated macrophage surface components during internalization of tachyzoites of Toxoplasma gondii was analyzed using neuraminidase, phospholipase C, trypsin, protease, and hyaluronidase. Treatment of these macrophages with neuraminidase from Vibrio cholerae, phospholipase C from Bacillus cereus and Clostridium perfringens, protease, and hyaluronidase prior to their interaction with parasites increased the penetration of host cells by T. gondii. Incubation of macrophages with trypsin significantly inhibited the uptake of parasites. Our findings confirm previous observations that treatment of the macrophages with cytochalasin D under conditions that completely block the typical phagocytic process partially inhibits infection of the cells by T. gondii. The results of simultaneous treatment of the macrophages with enzymes and cytochalasin D suggested that the observed enhancement of cell infection by treatment with neuraminidase and hyaluronidase was attributable to a classic phagocytic process, whereas that obtained using phospholipase resulted from active penetration. PMID- 8475029 TI - Pathologic effects of Sphaerospora dicentrarchi Sitja-Bobadilla and Alvarez Pellitero, 1992 and S. testicularis Sitja-Bobadilla and Alvarez-Pellitero, 1990 (Myxosporea: Bivalvulida) parasitic in the Mediterranean sea bass Dicentrarchus labrax L. (Teleostei: Serranidae) and the cell-mediated immune reaction: a light and electron microscopy study. AB - In the present study, the pathogenic effects of Sphaerospora dicentrarchi and S. testicularis, histozoic and coelozoic myxosporean parasites of the Mediterranean sea bass Dicentrarchus labrax L., respectively, are described. The infection caused by the latter, which usually invades the testes and neighboring tissues, is considered to represent parasitic castration. S. dicentrarchi seems to be harmless except in massive infections, which probably result in organic disfunctions. The cellular host reaction generated by S. testicularis depends on the location of the parasite and is more intense than that produced by S. dicentrarchi. In both sphaerosporoses, macrophages, granulocytes, lymphocytes, plasmacytes, and fibroblast-like cells are involved. The role of the different immune cells is discussed. PMID- 8475030 TI - Echinostoma trivolvis: mating behavior of adults raised in hamsters. AB - Echinostoma trivolvis adults grown in golden hamsters were treated in vitro with [3H]-tyrosine to label sperm and transplanted to uninfected hamsters alone or with four to six unlabeled adults. After 4-5 days, worms were recovered, processed for autoradiography, and observed for silver grains over their seminal receptacles. Of 11 worms transplanted singly, 6 (55%) self-inseminated. In multiple-worm situations, 7 of 12 (58%) labeled worms self-inseminated, and in the process the 12 labeled worms inseminated only 5 of 35 (14%) possible unlabeled worms. E. trivolvis adults self-inseminated when isolated and both self and cross-inseminated in groups, suggesting an unrestricted mating pattern. These results were compared with the mating patterns of other digenetic trematodes. PMID- 8475031 TI - Cloning and sequencing of a cDNA fragment from Plasmodium chabaudi chabaudi that contains repetitive sequences coding for a potentially lysine-rich aspartic acid rich protein. AB - Screening of a cDNA library (prepared in lambda gt11) of the blood stages of Plasmodium chabaudi chabaudi (AS) with immune serum has revealed an antigen the elicits a strong antibody response in infected mice. The clone (clone 6) expressing that antigen contains a 0.7 kb insert and produces a beta galactosidase fusion protein of about 150 kDa. In Western blot analysis performed on parasite extracts, monoclonal antibodies and polyclonal sera prepared against the fusion protein revealed that the fusion protein contains part of a malarial protein of 93 kDa. Northern hybridization with clone 6 insert as probe detected a plasmodial RNA of about 3.2 kb, which could well code for a protein of this size. The insert hybridized to a single EcoRI fragment and a single HindIII fragment in genomic Southern blotting, suggesting that the gene is present in one copy in the P. chabaudi genome. The DNA sequence of clone 6 insert predicts a hydrophilic, acidic polypeptide consisting of seven repeats of 23-34 amino acids rich in lysine (24%) and aspartic acid (17.5%). PMID- 8475032 TI - Interaction between trophozoites of Entamoeba histolytica and the human intestinal cell line HT-29 in the presence or absence of leukocytes. AB - Studies on the interaction between trophozoites of Entamoeba histolytica of pathogenic or non-pathogenic origin and epithelial cells of the human intestine can contribute to the understanding of the pathogenesis of invasive amoebiasis. We have examined the interaction of virulent E. histolytica with the human colonic carcinoma cell line HT-29. Differentiated HT-29 cells are comparable to the mucosa cells to which E. histolytica attaches physiologically. Adherence between E. histolytica trophozoites and HT-29 cells was effectively inhibited by glycoconjugates containing galactose, indicating the importance of the 170-kDa lectin of E. histolytica in binding to intestinal cells. Adherence was not significantly inhibited by glycoconjugates containing N-acetyl-glucosamine, indicating that the 220-kDa lectin of E. histolytica is not involved in binding to HT-29 cells. The destruction of HT-29 cells by pathogenic E. histolytica was dependent on adherence. The destruction was enhanced when polymorphonuclear granulocytes were added to the E. histolytica trophozoites. PMID- 8475033 TI - Effects of microtubule inhibitors on protein synthesis in Plasmodium falciparum. AB - At low concentrations, both isomers of tubulozole (C, T) inhibit Plasmodium falciparum but only tubulozole C inhibits mammalian cells. Since tubulozole C prevents polymerization of mammalian tubulin whereas tubulozole T does not, the antimalarial action of tubulozoles may not involve microtubules. The present study concerns the inhibition of parasite protein synthesis by the tubulozoles. While tubulozoles took 3-4 h to kill parasites in erythrocytic culture, they inhibited protein synthesis within 10 min. The concentrations of the drug required were, however, too high for this to account for their antimalarial action. The microtubule inhibitor colcemid inhibited protein synthesis rapidly and at relevant concentrations, but vinblastine did not inhibit protein synthesis. Tubulozole T and colcemid inhibited protein synthesis posttranscriptionally since they had little effect on RNA synthesis. Analysis of labelled parasite proteins by two-dimensional gel electrophoresis showed that while it inhibited synthesis of most proteins to the same degree, tubulozole T super-inhibited the synthesis of certain proteins. This may cause its antimalarial effect at low concentrations. PMID- 8475034 TI - Expression of sequences related to c-myc in Entamoeba. AB - The evolutionarily conserved proto-oncogene c-myc is involved in both proliferation and differentiation processes of higher eukaryotic cells. We report here the identification and characterization of sequences homologous to c-myc in different Entamoeba species using a fragment of the mammalian c-myc gene as a probe. This probe hybridized with fragments of 3.5 and 3.4 kilobases (kb) in E. histolytica HindIII of EcoRI digested DNA. In E. invadens it recognized fragments of 3.1 and 2.8 kb, and in Laredo strain (reported as E. moshkovskii by Clark and Diamond in 1991) the probe hybridized with fragments of 17 kb. The c-myc probe identified transcripts of 3.3 and 1.5 kb in E. histolytica, transcripts of 1.8 and 1.3 kb in Laredo strain, and transcripts of 3.7, 1.8, 1.5 and 1.1 kb in E. invadens. Antibodies against a highly conserved region of the c-myc protein recognized in E. histolytica polypeptides of 35, 40, and 60 kDa. The expression of the 60 kDa polypeptide was temperature-inducible in Laredo strain. In E. invadens a 110 kDa strong band was detected by the antibodies. Surprisingly, E. invadens myc-like sequences and proteins showed greater homology to mammalian c myc gene and proteins. Expression of proteins antigenically related to c-myc varied according to the cell cycle phase of E. histolytica. These proteins peaked during D, G1, and S phases and declined during G2. PMID- 8475035 TI - Phagocytosis and proteinase activity are not related to pathogenicity of E. histolytica. AB - To examine the relationship between phagocytosis, proteinase activity and pathogenicity of axenically grown trophozoites of E. histolytica strain HM-1:IMSS four different cultures were used: (1) a culture preserved in our laboratory for over 4 years, which lost its pathogenicity 3 years ago; (2) a culture passaged several times through hamster liver, which lost its pathogenicity recently; (3) a highly virulent culture supplied by another laboratory; and (4) amebas recovered from hamster liver abscesses caused by culture 3. Phagocytosis was measured as erythrophagocytosis. Proteinase activity was determined on azocasein. Pathogenicity was defined as the capacity to cause liver abscesses in hamsters. A negative correlation was found between phagocytic activity and pathogenicity, since amebas unable to cause liver abscesses had the highest phagocytic activity, whereas those recovered from liver abscesses had the lowest phagocytic activity. The percent of phagocytic amebas showed wide variations through a 2-month observation period, with no change in amebic pathogenicity. No correlation was found between the level of proteinase activity and pathogenicity. It is concluded that neither phagocytosis nor proteinase activity is an adequate marker of amebic pathogenicity. PMID- 8475036 TI - Circulating stable antigens at higher levels down-regulate antibody responses to Plasmodium falciparum. AB - A study involving 169 schoolchildren (5-14 years old) living in Manarintsoa near Antananarivo (Madagascar, East Africa) was performed during the seasonal malaria transmission period. For the whole population examined, the prevalence of Plasmodium falciparum and the rates of spleen enlargement and of circulating stable antigen (S-Ag) were found to be 60.9%, 71.7%, and 46.8%, respectively. The prevalence of IgG antibody to RESA (ring-infected erythrocyte surface antigen) was 42.7% and that of IgG and IgM antibodies to E-Ag (exoantigens) was 44.9% and 2.9%, respectively. The positive rates for IgG and IgM antibodies to Som-Ag (somatic antigen) were 48.5% and 5.9%, respectively. Concerning S-Ag, no significant relationship was observed for parasitemia, spleen size, age, or IgM antibody responses to exoantigens (E-Ag) or to somatic antigen (Som-Ag). Levels of S-Ag were found to be related to IgG antibodies to E-Ag. Our results suggest that S-Ag at low levels may participate in the mechanisms involved in the development of the IgG antibody responses to E-Ag and to Som-Ag, whereas at a comparative population level, higher quantities of S-Ag down-regulate antibody responses to P. falciparum. The data we obtained were compared with those gathered in another malaria mesoendemic area (Bobo-Dioulasso, Burkina Faso, West Africa), where lower levels of S-Ag were found. PMID- 8475037 TI - Proteinases resistant to sodium dodecyl sulfate-induced autoproteolysis of Entamoeba histolytica HK9 trophozoites. PMID- 8475038 TI - Inhibition of Glossina morsitans midgut trypsin activity by D-glucosamine. AB - The effect of the amino sugar D-glucosamine on trypsin in crude midgut homogenates of Glossina morsitans morsitans was studied in vitro. The results showed that the midgut trypsin was specifically and competitively inhibited by D Glucosamine. Glucose, fructose, mannose, inositol, galactose, galactosamine, N acetyl-D-glucosamine, and methyl-alpha-D-glucosamine were ineffective as inhibitors, even at concentrations exceeding 600 mM. D-glucosamine also had a similar inhibitory effect on bovine pancreatic trypsin. In both cases, the inhibition was incomplete as shown by nonlinear Dixon plots. The Michaelis and inhibition constants estimated for the midgut trypsin were 41 +/- 2 microM and 68 +/- 3 mM, respectively. These results suggest that the susceptibility of tsetse flies to trypanosome infection, which is associated with high midgut glucosamine levels, could be due to inhibition of trypsin or trypsin-like enzymes by this sugar. PMID- 8475039 TI - Species and strain differentiation of Eimeria spp. of the domestic fowl using DNA polymorphisms amplified by arbitrary primers. AB - Eimeria spp. from the domestic fowl were examined for genetic relatedness by the random amplified polymorphic DNA (RAPD) assay. Nine different oligonucleotide decamers with arbitrary DNA sequences were tested as primers to amplify DNA from six Eimeria species infecting chickens. Two strains each of E. acervulina and E. tenella were used. Depending on the species/strain-primer combination, between 1 and 12 DNA segments ranging in size from 0.16 to 4.95 kb were amplified. The two strains of E. acervulina showed minor and major differences in their amplified DNA patterns, giving a similarity coefficient of 61%. The two strains of E. tenella seemed to be more closely related, yielding a similarity coefficient of 98%. The differences observed between species were greater than those found between strains with every primer used, indicating that the RADP assay could be a useful tool for the study of relationships among these coccidia. The results obtained in this study also indicate the presence of unique, species-specific, amplified DNA segments that could be exploited to identify Eimeria species of the chicken. PMID- 8475040 TI - Molecular astrology: the case of the Myb DNA binding domain. PMID- 8475041 TI - Computer modelling of enzyme catalysed reaction mechanisms. PMID- 8475042 TI - Engineering cysteine mutants to obtain crystallographic phases with a cutinase from Fusarium solani pisi. AB - Cutinases are extracellular enzymes involved in the disruption of cutine, an insoluble polyester which covers the surface of plants. They belong to a class of serine esterases that are able to hydrolyse fatty acid esters and emulsified triglycerides as efficiently as lipases, but without displaying interfacial activation. Classical crystallographic methods for obtaining heavy-atom derivatives failed, so the cutinase structure has been solved exclusively by the multiple isomorphous replacement method using four Hg derivatives obtained from mutants S4C, S92C, S120C and S129C. Two of these derivatives behaved as expected: (i) the cys mutant of the catalytic Ser S120C, located at the surface of the active site pocket, leads to a good derivative; and (ii) the Hg atom of the derivative obtained with the S92C mutant is completely accessible to the solvent and occupies two alternative positions--consequently a poor derivative results. In contrast, two mutants show an unexpected behaviour: (i) the Hg atom in the S129C mutant was completely buried 10 A below the protein surface and yielded the best derivative; and (ii) a poor quality derivative was obtained with the S4C mutant. Cys 4 belongs to the disordered propeptide 1-16. The Cys 4 bound Hg atom is located in front of the Asp58 side chain, but neither Cys4 nor parts of the propeptide are clearly visible in the electron density maps of the derivative structure. PMID- 8475043 TI - Stabilization of lysozyme by the introduction of Gly-Pro sequence. AB - Three mutant lysozymes where the Asp101-Gly102 sequence of lysozyme was converted to Asp101-Pro102, Gly101-Pro102 and Pro101-Gly102 were prepared to investigate the effect of proline residues on the stabilization of proteins. The free energy changes of lysozymes for the unfolding in aqueous solution at pH 5.5 and 35 degrees C were 10.0, 10.1, 11.0 and 7.7 kcal/mol for wild type, Asp101Pro102, Gly101Pro102 and Pro101Gly102 lysozyme respectively. When the energy level in the unfolded state of wild type lysozyme was fixed at a standard level, the energy levels in the folded state of Asp101Pro102 and Pro101Gly102 lysozymes were found to be higher than that of wild type lysozyme on the basis of delta GD(H2O) and entropy losses of their polypeptide chains in the unfolded state. The presence of some strain in the folded state of these lysozymes was supported by both the calculation of conformational energy for a trans-L-prolyl residue [Schimmel, P.R. and Flory, P.J. (1968) J. Mol. Biol., 34, 105-120] and the analysis of structures of energy-minimized mutant lysozymes. Therefore, it is concluded that the formation of the Gly-Pro sequence is effective in avoiding possible strain in the folded state of a protein caused by the introduction of proline residue(s). PMID- 8475044 TI - Characterization of the DNA binding domain of the mouse IRF-2 protein. AB - The DNA binding domain of the interferon regulatory factor-2 protein (IRF-2) has been produced and characterized. alpha-chymotrypsin digestion of the purified IRF 2 protein bound to a synthetic binding site yields a peptide fragment of 14 K in molecular weight. N-terminal analysis of this peptide fragment showed that its sequence is the same as that of the intact IRF-2. A peptide fragment of approximately 14 K, IRF-2(113), which corresponds to the N-terminal 113 amino acids of the intact IRF-2 protein, has been expressed in a functional form in Escherichia coli. The first methionine was processed during the expression and the purified IRF-2(113) thus contains 112 amino acids. DNase I footprinting and gel retardation assaying showed that IRF-2(113) binds to a synthetic DNA having the consensus binding site and to the upstream regulatory sequence of the IFN beta gene as intact IRF-2 does. These results showed that this peptide fragment, IRF-2(113), may be a good material for investigation of the DNA binding domain of IRF-2 and of the DNA-protein interaction. PMID- 8475045 TI - Lysines 72, 80 and 213 and aspartic acid 210 of the Lactococcus lactis LacR repressor are involved in the response to the inducer tagatose-6-phosphate leading to induction of lac operon expression. AB - Site-directed mutagenesis of the Lactococcus lactis lacR gene was performed to identify residues in the LacR repressor that are involved in the induction of lacABCDFEGX operon expression by tagatose-6-phosphate. A putative inducer binding domain located near the C-terminus was previously postulated based on homology studies with the Escherichia coli DeoR family of repressors, which all have a phosphorylated sugar as inducer. Residues within this domain and lysine residues that are charge conserved in the DeoR family were changed into alanine or arginine. The production of the LacR mutants K72A, K80A, K80R, D210A, K213A and K213R in the LacR-deficient L.lactis strain NZ3015 resulted in repressed phospho beta-galactosidase (LacG) activities and decreased growth rates on lactose. Gel mobility shift assays showed that the complex between a DNA fragment carrying the lac operators and LacR mutants K72A, K80A, K213A and D210A did not dissociate in the presence of tagatose-6-phosphate, in contrast to wild type LacR. Other mutations (K62A/K63A, K72R, K73A, K73R, T212A, F214R, R216R and R216K) exhibited no gross effects on inducer response. The results strongly suggest that the lysines at positions 72, 80 and 213 and aspartic acid at position 210 are involved in the induction of lac operon expression by tagatose-6-phosphate. PMID- 8475046 TI - Engineering cytochrome P-450cam to increase the stereospecificity and coupling of aliphatic hydroxylation. AB - Site-directed mutants were constructed in cytochrome P-450cam to re-engineer the stereochemistry and coupling of ethylbenzene hydroxylation. The reaction with wild-type (WT) enzyme produces one regioisomer 1-phenylethanol with 5% reduced nicotinamide adenine deoxyribonucleic acid to product conversion of and a ratio of 73:27 for the R and S enantiomers respectively. Ethylbenzene was modeled into the active site of WT P-450cam in a rigid mode and oriented to optimize either pro-R or pro-S hydrogen abstraction. Residues T101, T185 and V247 make extensive contacts with the substrate in the static complexes and were therefore chosen for site-directed mutagenesis. Single mutants T101M, V247A and V247M are more stereospecific producing 89, 87 and 82% (R)-1-phenylethanol respectively. The coupling of the reaction is doubled for the single mutants T185L, T185F and V247M. In an effort to engineer increased stereospecificity and coupling into a single catalyst the T101M, T185F and V247M mutants were combined in a multiple mutant of P-450cam. This protein hydroxylates ethylbenzene resulting in an R:S ratio of 87:13 for the 1-phenylethanols and 13% coupling of reducing equivalents to product. The catalytic stereospecificity and stoichiometry with T101M--T185F- V247M does not represent a summation of the changes observed for the single mutants. A portion of the individual effects on substrate recognition produced by the single substitutions is either eliminated or degenerate within the triple mutant. PMID- 8475047 TI - Expression of functional papain precursor in Saccharomyces cerevisiae: rapid screening of mutants. AB - A microbial expression system for the study of the cysteine protease papain has been developed as a more useful alternative to the insect cell/baculovirus expression system we have previously used. A synthetic papain precursor (propapain) gene was expressed in the yeast Saccharomyces cerevisiae under the control of the alpha-factor promoter. Efficient expression required fusion of the propapain sequence with the yeast alpha-factor prepro region and a yeast host cell defective in the synthesis of vacuolar proteases. Surprisingly, the glycosylated form of the inactive papain precursor is not secreted, but accumulates within the yeast cell. Complete conversion of the intracellular zymogen into active mature papain could be achieved in vitro. Purified recombinant papain produced by the yeast system has kinetic characteristics similar to those of the natural enzyme. An advantage of the yeast expression system over the baculovirus/insect cell system is that we can perform mutagenesis and screening of papain mutants very efficiently. We have set up a 'one-tube' screening procedure for the simultaneous characterization of numerous mutants of the papain precursor. Yeast cells are grown and lysed in microtiter plate wells and the released papain precursor is then activated to mature papain. This assay allows easy discrimination between proteins with close to wild type properties and proteins that are not functional. We have applied this assay to investigate the spectrum of amino acids which are tolerated at Asn175 of papain using two independently derived libraries of mutants at this position. Many amino acid substitutions at this position are not accepted; only the reintroduction of Asn restored normal function. PMID- 8475048 TI - Overexpression and purification of avian ovomucoid third domains in Escherichia coli. AB - Genetic engineering studies of ovomucoid domains have been hindered by the lack of an efficient procedure for overproducing this protein. The novel scheme presented here has led to the isolation of chicken ovomucoid third domain (OMCHI3) at a level of 22 mg pure protein/l Escherichia coli culture medium. The gene coding for OMCHI3 was fused to the 3' end of the gene encoding staphylococcal nuclease (SNase). Expression of the chimeric gene was placed under control of the strong transcription and translation signals of the phage T7 promoter. Upon isopropyl-beta-D-galactopyranoside induction, the cells harboring the target plasmid efficiently overproduced the protein (30% of the total soluble protein). The 56-residue fragment corresponding to OMCHI3 was then liberated by cyanogen bromide (CNBr) cleavage at a genetically engineered methionine residue located at the nuclease--OMCHI3 junction (OMCHI3 lacks an internal methionine). SDS--PAGE, enzyme inhibition studies and NMR spectroscopy all indicated that the recombinant OMCHI3 has properties identical to those of OMCHI3 isolated from its natural source. The expression system was easily adapted for the production of [98% U 15N] OMCHI3. The expression vector was mutated for overexpression of turkey ovomucoid third domain (OMTKY3), which differs from OMCHI3 by three amino acid substitutions. Since many other avian ovomucoid domains also lack methionine residues, this approach should be suitable for large-scale production and isotope labeling of homologous proteinase inhibitors with a variety of inhibitory specificities. PMID- 8475049 TI - Agrobacterium gene transfer: progress on a "poor man's vector" for maize. PMID- 8475050 TI - Nuclear magnetic resonance imaging and spectroscopy of human brain function. AB - The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral vasculature has allowed measurements of regional cerebral blood volume (rCBV), which are activity dependent. Subsequent investigations linked the MR relaxation properties of brain tissue to blood oxygenation levels which are also modulated by consumption and blood flow (rCBF). These methods have allowed mapping of brain activity in human visual and motor cortex as well as in areas of the frontal lobe involved in language. The methods have high enough spatial and temporal sensitivity to be used in individual subjects. MR spectroscopy of proton and carbon-13 nuclei has been used to measure rates of glucose transport and metabolism in the human brain. The steady-state measurements of brain glucose concentrations can be used to monitor the glycolytic flux, whereas subsequent glucose metabolism--i.e., the flux into the cerebral glutamate pool--can be used to measure tricarboxylic acid cycle flux. Under visual stimulation the concentration of lactate in the visual cortex has been shown to increase by MR spectroscopy. This increase is compatible with an increase of anaerobic glycolysis under these conditions as earlier proposed from positron emission tomography studies. It is shown how MR spectroscopy can extend this understanding of brain metabolism. PMID- 8475051 TI - Strategies to protect crop plants against viruses: pathogen-derived resistance blossoms. AB - Since 1986, the ability to confer resistance against an otherwise devastating virus by introducing a single pathogen-derived or virus-targeted sequence into the DNA of a potential host plant has had a marked influence on much of the research effort, focus, and short-term objectives of plant virologists throughout the world. The vast literature on coat protein-mediated protection, for example, attests to our fascination for unraveling fundamental molecular mechanism(s), our (vain) search for a unifying hypothesis, our pragmatic interest in commercially exploitable opportunities for crop protection, and our ingenuity in manipulating transgene constructions to broaden their utility and reduce real or perceived environmental risk issues. Other single dominant, pathogen-derived plant resistance genes have recently been discovered from a wide variety of viruses and are operative in an ever-increasing range of plant species. Additional candidates seem limited only by the effort invested in experimentation and by our ingenuity and imagination. This review attempts to consider, in a critical way, the current state of the art, some exceptions, and some proposed rules. The final impression, from all the case evidence considered, is that normal virus replication requires a subtle blend of host- and virus-coded proteins, present in critical relative concentrations and at specific times and places. Any unregulated superimposition of interfering protein or nucleic acid species can, therefore, result in an apparently virus-resistant plant phenotype. PMID- 8475052 TI - Cell-specific regulation of apoptosis by designed enediynes. AB - The naturally occurring enediyne antibiotics are a unique class of antitumor drugs that combine reactive enediynes with additional structural features conferring affinity for DNA. Dynemicin A, in which an enediyne core is attached to an anthraquinone group capable of DNA intercalation, readily cleaves double stranded DNA. This activity is thought to be the basis of its potent antitumor cytotoxicity. To investigate cell-specific mechanisms of cytotoxicity in the absence of DNA affinity, we have synthesized a variety of dynemicin-like enediynes that lack the anthraquinone moiety. We have found that the cytotoxicity of these compounds is dependent on their chemical instability and their enantiomeric form. Their selective toxicity results from a potent induction of apoptosis primarily in human leukemic cells. A group of synthetic enediynes were designed to be highly stable. These compounds were found to inhibit apoptotic cell death. This inhibition was observed in competition with the chemically unstable enediynes, including dynemicin and calicheamicin. The stable synthetic enediynes could also block the apoptotic morphology induced by unrelated cytotoxic agents such as cycloheximide, actinomycin D, and ultraviolet radiation. The results suggest that the cellular target(s) of synthetic enediynes may play a central role in regulating programmed cell death; a specific receptor-ligand interaction is proposed. PMID- 8475053 TI - T7 RNA polymerase mutants with altered promoter specificities. AB - The amino acid at position 748 in T7 RNA polymerase (RNAP) functions to discriminate base pairs at positions -10 and -11 in the promoter. We have constructed a series of T7 RNAP mutants having all possible amino acid substitutions at this position. Surprisingly, most (13/19) substitutions result in active RNAPs, and many of these exhibit altered promoter specificities. Identification of mutant RNAPs with altered specificities expands the repertoire of highly specific phage RNAPs that are available for use in phage RNAP-based transcription systems and highlights the complexity of sequence-specific DNA recognition. PMID- 8475054 TI - Identification and characterization of a nuclease activity specific for G4 tetrastranded DNA. AB - We have identified a nuclease activity that is specific for G4 tetrastranded DNA. This activity, found in a partially purified fraction for a yeast telomere binding protein, binds to DNA molecules with G4 tetrastranded structure, regardless of their nucleotide sequences, and cleaves the DNA in a neighboring single-stranded region 5' to the G4 structure. Competition with various G4-DNA molecules inhibits the cleavage reaction, suggesting that this nuclease activity is specific for G4 tetrastranded DNA. The existence of this enzymatic activity that reacts with G4 DNAs but not with single-stranded or Watson-Crick duplex DNAs suggests that tetrastranded DNA may have a distinct biological function in vivo. PMID- 8475055 TI - Osteocalcin gene promoter-binding factors are tissue-specific nuclear matrix components. AB - The nuclear matrix appears to play an important role in developmental gene expression during osteoblast differentiation. To better understand this role, we examined nuclear matrix DNA-binding proteins that are sequence-specific and interact with the osteocalcin gene promoter. Multiple protein-DNA interactions involving two distinct nuclear matrix proteins occur within the 5' regulatory sequences (nt -640 to -430). One of these proteins, NMP-1, is a ubiquitous, cell growth-regulated protein that is related to the transcription factor ATF and resides in both the nuclear matrix and the nonmatrix nuclear compartment. The other protein, NMP-2, is a cell type-specific, 38-kDa promoter factor that recognizes binding sites resembling the consensus site for the CCAAT/enhancer binding protein C/EBP and is localized exclusively on the nuclear matrix. NMP-1 and NMP-2 each interact with two nuclear matrix protein-binding elements. These elements are present near key regulatory sites of the osteocalcin gene promoter, such as the principal steroid hormone (vitamin D)-responsive sequences. Binding in this region of the osteocalcin gene promoter suggests transient associations with the nuclear matrix that are distinct from the stable interactions of matrix attachment regions. Our results are consistent with involvement of the nuclear matrix in concentrating and/or localizing transcription factors that mediate the basal and steroid hormone responsiveness of osteocalcin gene transcription. PMID- 8475057 TI - Dating the genetic bottleneck of the African cheetah. AB - The cheetah is unusual among fields in exhibiting near genetic uniformity at a variety of loci previously screened to measure population genetic diversity. It has been hypothesized that a demographic crash or population bottleneck in the recent history of the species is causal to the observed monomorphic profiles for nuclear coding loci. The timing of a bottleneck is difficult to assess, but certain aspects of the cheetah's natural history suggest it may have occurred near the end of the last ice age (late Pleistocene, approximately 10,000 years ago), when a remarkable extinction of large vertebrates occurred on several continents. To further define the timing of such a bottleneck, the character of genetic diversity for two rapidly evolving DNA sequences, mitochondrial DNA and hypervariable minisatellite loci, was examined. Moderate levels of genetic diversity were observed for both of these indices in surveys of two cheetah subspecies, one from South Africa and one from East Africa. Back calculation from the extent of accumulation of DNA diversity based on observed mutation rates for VNTR (variable number of tandem repeats) loci and mitochondrial DNA supports a hypothesis of an ancient Pleistocene bottleneck that rendered the cheetah depauperate in genetic variation for nuclear coding loci but would allow sufficient time for partial reconstitution of more rapidly evolving genomic DNA segments. PMID- 8475056 TI - Differentiation-dependent activation of interferon-stimulated gene factors and transcription factor NF-kappa B in mouse embryonal carcinoma cells. AB - We have recently shown that the adenovirus E1A gene products block interferon alpha-induced signal transduction and transcription factor NF-kappa B-mediated gene induction. Here we report that the same responses are also blocked in undifferentiated F9 teratocarcinoma cells. The block was removed upon cellular differentiation and regained upon the introduction of viral E1A into the differentiated cells. In undifferentiated cells, interferon-beta failed to induce the transcription of interferon-responsive genes because of a lack of activation of the cognate trans-acting factors. As a result, in these cells, virus replication was not inhibited by interferon. Similarly, in undifferentiated but not in differentiated F9 cells, tumor necrosis factor alpha failed to stimulate NF-kappa B-mediated transcription of a reporter gene because of a failure in the activation of NF-kappa B trans-acting factor. These results suggest that a cellular E1A-like activity, present in undifferentiated F9 cells, and adenoviral E1A use similar mechanisms for repressing the expression of specific cellular genes. PMID- 8475058 TI - Lethal thalassemia after insertional disruption of the mouse major adult beta globin gene. AB - Thalassemias are hereditary anemias caused by mutations that disturb the normal 1:1 balance of alpha- and beta-globin chains that form hemoglobin. We have disrupted the major adult beta-globin gene (b1) in mouse embryonic stem cells by using homologous recombination to insert selectable sequences into the gene. Mice homozygous for this insertional disruption of the b1 gene (Hbbth-2/Hbbth-2) are severely anemic and die perinatally. In contrast, approximately 60% of mice homozygous for deletion of the same gene (Hbbth-1/Hbbth-1) survive to adulthood and are much less anemic [Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Goldberg, S. Z., Anderson, W. F., Barnett, L. B. & Lewis, S. E. (1983) Cell 34, 1043-1052]. These different phenotypes have implications for the control of beta-globin gene expression. PMID- 8475059 TI - Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells. AB - The only known component of the infectious prion is a posttranslationally modified protein known as the scrapie isoform of the prion protein, PrPSc. Upon limited proteolysis, a protease-resistant fragment designated PrP 27-30 is formed. Using in vitro mutagenesis, we examined the role of the N and C termini in the formation of PrPSc in persistently infected, mouse neuroblastoma (ScN2a) cells. Neither deletion of amino acids 23-88, which are also removed by proteinase K in the formation of PrP 27-30, nor deletion of the five octapeptide repeats within this region altered synthesis of PrPSc. Elongation of PrP with one, two, four, or six octapeptide repeats in addition to the five found in wild type PrP did not alter the synthesis of PrPSc. Truncation of the C terminus was accomplished by substituting a translation stop codon for the predicted glycosylinositol phospholipid (GPI) anchor-attachment signal corresponding to amino acids 231-254. Expression of this C-terminal PrP mutant in ScN2a cells produced PrPSc that appeared to lack a GPI anchor. We conclude that neither the GPI anchor nor the N-terminal 66 amino acids are required for the synthesis of PrPSc as measured by the acquisition of limited resistance to proteinase K digestion. Whether these truncated or elongated PrP molecules are competent to participate in the formation of infectious prions remains to be established. PMID- 8475060 TI - Calcium influx mediated by the Escherichia coli heat-stable enterotoxin B (STB). AB - The heat-stable enterotoxin B (STB) of Escherichia coli is a 48-amino acid extracellular peptide that induces rapid fluid accumulation in animal intestinal models. Unlike other E. coli enterotoxins that elicit cAMP or cGMP responses in the gut [heat-labile toxin (LT) and heat-stable toxin A (STA), respectively], STB induces fluid loss by an undefined mechanism that is independent of cyclic nucleotide elevation. Here we studied the effects of STB on intracellular calcium concentration ([Ca2+]i), another known mediator of intestinal ion and fluid movement. Ca2+ and pH measurements were performed on different cell types including Madin-Darby canine kidney (MDCK), HT-29/C1 intestinal epithelial cells, and primary rat pituitary cells. Ca2+ and pH determinations were performed by simultaneous real-time fluorescence imaging at four emission wavelengths. This allowed dual imaging of the Ca(2+)- and pH-specific ratio dyes (indo-1 and SNARF 1, respectively). STB treatment induced a dose-dependent increase in [Ca2+]i with virtually no effect on internal pH in all of the cell types tested. STB-mediated [Ca2+]i elevation was not inhibited by drugs that block voltage-gated Ca2+ channels including nitrendipine, verapamil (L-type), omega-conotoxin (N-type), and Ni2+ (T-type). The increase in [Ca2+]i was dependent on a source of extracellular Ca2+ and was not affected by prior treatment of MDCK cells with thapsigargin or cyclopiazonic acid, agents that deplete and block internal Ca2+ stores. In contrast to these results, somatostatin and pertussis toxin pretreatment of MDCK cells completely blocked the STB-induced increase in [Ca2+]i. Taken together, these data suggest that STB opens a GTP-binding regulatory protein-linked receptor-operated Ca2+ channel in the plasma membrane. The nature of the STB-sensitive Ca2+ channel is presently under investigation. PMID- 8475061 TI - Assembly of a functional replication complex without ATP hydrolysis: a direct interaction of bacteriophage T4 gp45 with T4 DNA polymerase. AB - The seven-protein bacteriophage T4 DNA replication complex can be manipulated in vitro to study mechanistic aspects of the elongation phase of DNA replication. Under physiological conditions, the processivity of DNA synthesis catalyzed by the T4 polymerase (gp43) is greatly increased by the interaction of this enzyme with its accessory proteins (gp44/62 and gp45) and the T4 single-stranded DNA binding protein (gp32). The assembly of this T4 holoenzyme requires hydrolysis of ATP by the gp44/62 complex. We demonstrate here that processive T4 holoenzyme like DNA synthesis can be obtained without hydrolysis of ATP by simply adding gp45 to the T4 DNA polymerase at extremely high concentrations, effectively bypassing the ATPase subunits (gp44/62) of the accessory protein complex. The amount of gp45 required for the gp43-gp45 heteroassociation event is reduced by addition of the macromolecular crowding agent polyethylene glycol (PEG) as well as gp32. A chromatographic strategy involving PEG has been used to demonstrate the gp43-gp45 interaction. These results suggest that gp45 is ultimately responsible for increasing the processivity of DNA synthesis via a direct and functionally significant interaction with the T4 DNA polymerase. A corollary to this notion is that the specific role of the gp44/62 complex is to catalytically link gp45 to gp43. PMID- 8475062 TI - Clonal ordering of 17p and 5q allelic losses in Barrett dysplasia and adenocarcinoma. AB - Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus. PMID- 8475063 TI - A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7. AB - The pathogenesis of vascular disease is unclear, but genetic factors play an important role. In this study we performed linkage analyses in two families with supravalvular aortic stenosis, an inherited vascular disorder that causes narrowing of major arteries and may lead to cardiac overload and failure. DNA markers on the long arm of chromosome 7 (D7S371, D7S395, D7S448, and ELN) were linked to supravalvular aortic stenosis in both families with a combined logarithm of likelihood for linkage (lod score) of 5.9 at the ELN locus. These findings indicate that a gene for supravalvular aortic stenosis is located in the same chromosomal subunit as elastin, which becomes a candidate for the disease gene. PMID- 8475064 TI - CD22 associates with the human surface IgM-B-cell antigen receptor complex. AB - The B-cell surface molecule CD22, when cross-linked, modulates signaling through the surface IgM (sIgM)-B-cell receptor (BCR) complex. Here we analyzed the basis of this interaction between CD22 and the human sIgM complex. After lysis of B cells or B-cell lines in digitonin, CD22 coimmunoprecipitated a kinase activity that in vitro-phosphorylated two polypeptides of 150 and 130 kDa on tyrosine residues. By immunoblot analysis with a rabbit anti-serum specific for a synthetic peptide of CD22, we found these proteins to be CD22 itself. Furthermore, the phosphorylated 150-kDa CD22 was found in the sIgM-BCR complex maintained by digitonin, along with Ig alpha/mb-1, Ig beta/B29, and a 75-kDa polypeptide precipitated by an antiserum specific to protein-tyrosine kinase PTK72. CD22 is likely to be an important signaling partner in the sIgM-BCR complex since it is very rapidly and strikingly phosphorylated after sIgM is cross-linked and since it contains the antigen recognition homology I (ARHI) motif, present in other antigen receptor molecules. PMID- 8475066 TI - Direction of handedness linked to hereditary asymmetry of a sensory system. AB - Studies on the role of heredity in the transmission of handedness in nonhuman mammals have, so far, led to the isolation of mouse strains that differed in the lateralized versus ambidextrous use of the forepaw in a food-retrieval task (strength of paw preference). Here we report that left versus right use of the forepaw (direction of paw preference) is associated with a genetically expressed structural asymmetry of a sensory system, the whisker-to-barrel pathway. Mice that express whisker pad asymmetry of a direction that corresponds with the asymmetry for which they were bred demonstrate an opposite shift in the distribution of handedness: a right or left dominance of the whisker pad predicts a high proportion of left-handers or right-handers, respectively. Is an altered brain circuit--that is, a consequence of the asymmetry of the whisker pad- associated with a change in the circuitry that governs handedness? Or, alternatively, are there two gene sets responsible for the phenomena that we report--one that causes "whiskeredness" and another that causes handedness? PMID- 8475065 TI - Beta-arrestin and arrestin are recognized by autoantibodies in sera from multiple sclerosis patients. AB - Multiple sclerosis (MS), one of the most common chronic neurologic diseases, is characterized by the presence of multiple plaques of demyelination throughout the central nervous system. Although the etiology of the disease has not been established, it is believed to involve autoimmune mechanisms. We have examined sera from patients with MS for the presence of antibodies to antigens from brain and retina. Immunoblot analysis of soluble fraction of proteins from bovine brain revealed a prominent band at 45 kDa stained with sera of 8-14 patients with MS. In two patients with MS, serum antibody titers during relapse were higher compared with those when the patients were in remission. These antibodies were undetectable in cerebrospinal fluid of our MS patients and additionally were absent in sera of patients with other neurological diseases and normal control subjects. Furthermore, immunoblot analysis of the soluble fraction from bovine retinal rod outer segments revealed a prominent protein band at 48 kDa stained with MS sera. This antigen was purified to homogeneity from bovine retinal outer segments and identified as arrestin. Additionally, sera from MS patients reacted with purified beta-arrestin 1, a 45-kDa protein homologous to arrestin that is found in various tissues. Using limited proteolysis of arrestin and a competitive ELISA test with a synthetic peptide, we identified the recognition site(s) for antibodies in sera of MS patients at a dominant immunogenic site on arrestin located at the C-terminal region of the molecule. We suggest that the presence of circulating antibodies reactive with beta-arrestin or arrestin may be related to the course of MS progression. PMID- 8475067 TI - Precursor polyprotein for multiple neuropeptides secreted from the suboesophageal ganglion of the silkworm Bombyx mori: characterization of the cDNA encoding the diapause hormone precursor and identification of additional peptides. AB - Peptidergic neurons, which serve as source of various endocrine neuropeptides, were identified in the suboesophageal ganglion (SG) and brain of insects. In the silkworm Bombyx mori, SG is known to secrete two neuropeptides, diapause hormone (DH) responsible for induction of embryonic diapause and pheromone biosynthesis activating neuropeptide, which share a pentapeptide amide, Phe-Xaa-Pro-Arg-Leu NH2 (Xaa = Gly or Ser), at the C terminus. We have isolated cDNA clones for DH from the cDNA library of SG by using oligonucleotide probes. The molecular characterization of the cDNA reveals that the mRNA encodes an open reading frame consisting of 192 aa residues in which the 24-aa DH peptide is localized at the N terminal region just after the signal peptide. A homology search proposed that the cDNA encodes pheromone biosynthesis-activating neuropeptide and three other neuropeptides [alpha-, beta-, and gamma-SG neuropeptide (SGNP)] in the region following DH, all of which are flanked by possible tryptic cleavage sites and share the Phe-Xaa-Pro-Arg-Leu-Gly sequence at the C terminus. Northern hybridization analysis clearly showed that the gene expression was limited to SG. We chemically synthesized alpha-, beta-, and gamma-SGNP and used them to identify components in extracts of SG and to examine biological functions, alpha- and gamma-SGNP were identified in extracts of SG, and the synthetic beta- and gamma SGNP expressed weak DH activity. These results indicate that DH, along with four other neuropeptides, is generated from a common precursor polyprotein that is encoded by a single mRNA transcribed in neurosecretory cells of SG. PMID- 8475069 TI - The alpha aneurism: a structural motif revealed in an insertion mutant of staphylococcal nuclease. AB - The x-ray crystal structure of a mutant of staphylococcal nuclease that contains a single glycine residue inserted in the C-terminal alpha-helix has been solved to 1.67 A resolution and refined to a crystallographic R value of 0.170. This inserted glycine residue is accommodated in the alpha-helix by formation of a previously uncharacterized bulge, which we term the alpha aneurism. A conformational search of known protein structures has identified the alpha aneurism in a number of protein families, including the histocompatibility antigens and hemoglobins. PMID- 8475068 TI - Sp-1 binds promoter elements regulated by the RB protein and Sp-1-mediated transcription is stimulated by RB coexpression. AB - The retinoblastoma (RB) protein is implicated in transcriptional regulation of at least five cellular genes, including c-fos, c-myc, and transforming growth factor beta 1. Cotransfection of RB and truncated promoter constructs has defined a discrete element (retinoblastoma control element; RCE) within the promoters of each of these genes as being necessary for RB-mediated transcription control. Previously, we have shown that RCEs form protein-DNA complexes in vitro with three heretofore unidentified nuclear proteins and mutation of their DNA-binding site within the c-fos RCE results in an abrogation of RCE-dependent transcription in vivo. Here, we demonstrate that one of the nuclear proteins that binds the c fos, c-myc, and transforming growth factor beta 1 RCEs in vitro is Sp-1 and that Sp-1 stimulates RCE-dependent transcription in vivo. Moreover, we show that Sp-1 mediated transcription is stimulated by the transient coexpression of RB protein. We conclude from these observations that RB may regulate transcription in part by virtue of its ability to functionally interact with Sp-1. PMID- 8475070 TI - Separation between cytosolic calcium and secretion in chromaffin cells superfused with calcium ramps. AB - This paper describes experiments in which cytosolic Ca2+ concentrations ([Ca2+]i) and catecholamine release were measured in two populations of chromaffin cells stimulated with a solution enriched in K+ (100 mM). Once depolarized, external Ca2+ or Ba2+ ions were offered to cells either as a single 2.5 mM step or as a ramp that linearly increased the concentration from 0 to 2.5 mM over a 10-min period. A clear separation between the changes of the [Ca2+]i and the time course of secretion was observed. Specifically, secretion and [Ca2+]i rose in parallel when a Ca2+ step was used to reach a peak in a few seconds; however, while secretion declined to the basal level, [Ca2+]i remained elevated at a plateau of 400 nM. With a Ca2+ ramp, only a transient small peak of secretion was observed, yet the [Ca2+]i remained elevated throughout the 10-min stimulation period. The separation between secretion and [Ca2+]i was observed even when voltage-dependent Ca2+ channels were expected to remain open (mild depolarization in the presence of 1 microM Bay K 8644). By using Ba2+ steps or ramps, sustained noninactivating secretory responses were obtained. The results suggest that the rate and extent of secretion are not a simple function of the [Ca2+]i at a given time; they are compatible with the following conclusions: (i) A steep extracellular-to-cytosolic Ca2+ gradient is required to produce a sharp increase in the [Ca2+]i at exocytotic sites capable of evoking a fast but transient secretory response. (ii) As a result of Cai(2+)-dependent inactivation of Ca2+ channels, those high [Ca2+]i are possible only at early times after cell depolarization. (iii) The Cai(2+)-dependent supply of storage granules to the secretory machinery cooperates with the supply of Ca2+ through Ca2+ channels to regulate the rate and extent of secretion. PMID- 8475071 TI - Acquired multicellular-mediated resistance to alkylating agents in cancer. AB - EMT-6 murine mammary tumor sublines highly resistant to cyclophosphamide, cis diamminedichloro-platinum(II), or N,N',N"-triethylenethiophosphoramide were generated in vivo by sequential treatment of tumor-bearing mice with the respective drugs. Previous studies demonstrated the drug-resistant phenotypes of the sublines were not expressed in vitro when the cells were grown as monolayer cultures. We now show that expression of drug resistance--including patterns of cross-drug resistance observed in vivo--can be fully recapitulated in vitro when the cells are grown under in vivo-like, three-dimensional conditions--namely, as multicellular tumor spheroids. Moreover, the spheroids generated from all of the drug-resistant sublines manifested a much more compact structure. Immediate drug sensitivity testing of single cells released by trypsin treatment from compact drug-resistant spheroids revealed that such cells lost much of their drug resistant properties. The results suggest a possible mechanism of acquired drug resistance in tumors based on the response of a cell population (i.e., multicellular or tissue resistance) as opposed to classic (uni)cellular resistance mechanisms. PMID- 8475072 TI - Inhibition of rate of tumor growth by creatine and cyclocreatine. AB - Growth rate inhibition of subcutaneously implanted tumors results from feeding rats and athymic nude mice diets containing 1% cyclocreatine or 1%, 2%, 5%, or 10% creatine. The tumors studied included rat mammary tumors (Ac33tc in Lewis female rats and 13762A in Fischer 344 female rats), rat sarcoma MCI in Lewis male rats, and tumors resulting from the injection of two human neuroblastoma cell lines, IMR-5 and CHP-134, in athymic nude mice. Inhibition was observed regardless of the time experimental diets were administered, either at the time of tumor implantation or after the appearance of palpable tumors. For mammary tumor Ac33tc, the growth inhibition during 24 days after the implantation was approximately 50% for both 1% cyclocreatine and 1% creatine, and inhibition increased as creatine was increased from 2% to 10% of the diet. For the other rat mammary tumor (13762A), there was approximately 35% inhibition by both 1% cyclocreatine and 2% creatine. In the case of the MCI sarcoma, the inhibitory effect appeared more pronounced at earlier periods of growth, ranging from 26% to 41% for 1% cyclocreatine and from 30% to 53% for 1% creatine; there was no significant difference in growth rate between the tumors in the rats fed 1% and 5% creatine. The growth rate of tumors in athymic nude mice, produced by implantation of the human neuroblastoma IMR-5 cell line, appeared somewhat more effectively inhibited by 1% cyclocreatine than by 1% creatine, and 5% creatine feeding was most effective. For the CHP-134 cell line, 33% inhibition was observed for the 1% cyclocreatine diet and 71% for the 5% creatine diet. In several experiments, a delay in appearance of tumors was observed in animals on the experimental diets. In occasional experiments, neither additive inhibited tumor growth rate for the rat tumors or the athymic mouse tumors. PMID- 8475073 TI - Data base analysis of protein expression patterns during T-cell ontogeny and activation. AB - We have developed a data base of lymphoid proteins detectable by two-dimensional polyacrylamide gel electrophoresis. The data base contains two-dimensional patterns and derived information pertaining to polypeptide constituents of unstimulated and stimulated mature T cells and immature thymocytes, single-cell derived T- and B-cell clones, leukemia cells, and lymphoid cell lines. Using this data base, we have compared the protein constituents of mature T cells and immature thymocytes before and after mitotic stimulation. A subset of polypeptides that are induced in mature T cells following mitotic stimulation were found to be constitutively expressed in immature thymocytes. Other polypeptides exhibited differences in their expression between mature and immature thymocytes in a manner unrelated to proliferation. The identity of several constitutively expressed or mitotically induced proteins in lymphoid cells was established by microsequencing. These initial findings point to significant differences in the molecular pathways leading to proliferation between mature and immature T cells. The construction of this database should facilitate further studies of lymphoid differentiation and function. PMID- 8475074 TI - The p53 protein is an unusually shaped tetramer that binds directly to DNA. AB - We have analyzed the size and structure of native immunopurified human p53 protein. By using a combination of chemical crosslinking, gel filtration chromatography, and zonal velocity gradient centrifugation, we have determined that the predominant form of p53 in such preparations is a tetramer. The behavior of purified p53 in gels and sucrose gradients implies that the protein has an extended shape. Wild-type p53 has been shown to bind specifically to sites in cellular and viral DNA. We show in this study by Southwestern ligand blotting and by analysis of DNA-bound crosslinked p53 that p53 monomers, dimers, and tetramers can bind directly to DNA. PMID- 8475075 TI - Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization. AB - Cyclophilin is a binding protein for the immunosuppressive drug cyclosporin A and is also an enzyme with peptidyl-prolyl cis-trans isomerase activity. The crystal structure of cyclophilin A complexed with the substrate Ala-Pro has been determined and refined to an R factor of 0.196 at 1.64-A resolution. The structure shows that only the cis form of Ala-Pro binds cyclophilin A despite the fact that Ala-Pro has an equilibrium majority of the trans form in solution. Simulation of the cis-trans isomerization in an ESV10 graphics system suggests a solvent-assisted mechanism in which first the peptidyl-prolyl bond is desolvated at the ground state by binding to the hydrophobic pocket of the active site, and later the intermediate state is stabilized by a hydrogen bond between the carbonyl oxygen of the amide bond and a bound water molecule. PMID- 8475076 TI - Odor-induced increases in c-fos mRNA expression reveal an anatomical "unit" for odor processing in olfactory bulb. AB - Expression of the immediate-early gene c-fos was used to evaluate the coordinate activation of olfactory bulb neurons by brief exposure to specific odors in the alert rat. In situ hybridization to c-fos mRNA was compared to regional increases in 2-deoxy-D-[14C]glucose incorporation in an adjacent section analysis. Levels of c-fos mRNA in olfactory bulb were high in rats recently removed from their home cage but were low in animals placed in a relatively odor-free chamber for 30 min. Presentation of specific odors to alert rats for as little as 5 min increased c-fos mRNA in radially distributed neuronal ensembles that spanned the lamina of the main olfactory bulb. The complementary RNA (cRNA)-labeled neuronal collectives consisted of cells in the glomerular layer that precisely defined the borders of individual glomeruli and underlying tufted, mitral, and granule cells. The activated fields were much broader in the granule cell layer than in the overlying glomerular layer and thus exhibited a flask-like, as opposed to a columnar, contour. The bulbar distribution of cRNA-labeled cell arrays differed with different odors and, in the glomerular layer, corresponded to focal regions of high 2-deoxy-D-[14C]glucose uptake. Administration of the noncompetitive N methyl-D-aspartate receptor antagonist MK801 did not attenuate the odor induction of c-fos but, instead, increased c-fos mRNA levels throughout the bulb. We propose that the neuronal ensembles expressing increased c-fos mRNA with odor stimulation represent principal functional units of sensory processing in the main olfactory bulb of the behaving rat. PMID- 8475077 TI - Z-DNA binding protein from chicken blood nuclei. AB - A protein (Z alpha) that appears to be highly specific for the left-handed Z-DNA conformer has been identified in chicken blood nuclear extracts. Z alpha activity is measured in a band-shift assay by using a radioactive probe consisting of a (dC-dG)35 oligomer that has 50% of the deoxycytosines replaced with 5 bromodeoxycytosine. In the presence of 10 mM Mg2+, the probe converts to the Z DNA conformation and is bound by Z alpha. The binding of Z alpha to the radioactive probe is specifically blocked by competition with linear poly(dC-dG) stabilized in the Z-DNA form by chemical bromination but not by B-form poly(dC dG) or boiled salmon-sperm DNA. In addition, the binding activity of Z alpha is competitively blocked by supercoiled plasmids containing a Z-DNA insert but not by either the linearized plasmid or by an equivalent amount of the parental supercoiled plasmid without the Z-DNA-forming insert. Z alpha can be crosslinked to the 32P-labeled brominated probe with UV light, allowing us to estimate that the minimal molecular mass of Z alpha is 39 kDa. PMID- 8475078 TI - The nucleotide in position 32 of the tRNA anticodon loop determines ability of anticodon UCC to discriminate among glycine codons. AB - We have investigated the influence of structures in the tRNA anticodon loop and stem on the ability of the anticodon to discriminate among codons. We had previously shown that anticodon UCC, when placed in the structural context of tRNA(Gly1) from Escherichia coli, discriminated efficiently between the glycine codons, as required by the wobble rules. Thus, this anticodon read GGA and GGG but did not read GGU and GGC, whereas in mycoplasma tRNA(Gly), the same anticodon did not discriminate among the glycine codons. We have now determined the reading properties of three constructions based on tRNA(Gly1) containing the anticodon UCC in different structural contexts. In one of these constructs, tRNA(Gly1-ASL), the anticodon loop and stem are the same as in mycoplasma tRNA(Gly). The second construct, tRNA(Gly1-AS), has an anticodon stem identical with the mycoplasma tRNA(Gly), whereas in the last construct, tRNA(Gly1-C32), the only difference from tRNA(Gly1)(UCC) is that the uridine in position 32 of the anticodon loop has been replaced by cytidine. These constructs were tested for ability to read glycine codons in an in vitro protein-synthesizing system that allowed us to monitor separately the reading of each codon. We found that the anticodon UCC, when present in tRNA(Gly1-AS), discriminated among the glycine codons, whereas in the constructs tRNA(Gly1-ASL) and tRNA(Gly1-C32), the same anticodon had lost its ability to discriminate--i.e., it behaved as in mycoplasma tRNA(Gly). These results strongly suggest that nt 32 of the anticodon loop of tRNA(Gly1)(UCC) decisively influences the reading properties of the anticodon UCC. PMID- 8475079 TI - Regulated expression of an insulin-responsive glucose transporter (GLUT4) minigene in 3T3-L1 adipocytes and transgenic mice. AB - Preliminary studies showed that up to 7 kb of 5' flanking sequence of the insulin responsive glucose transporter (GLUT4) gene are insufficient to mediate differentiation-induced reporter gene expression in mouse 3T3-L1 preadipocytes. To locate the regulatory element(s) responsible for this function, a minigene containing the entire GLUT4 gene with substantial 5' and 3' flanking sequence and a short segment of foreign DNA (for transcript identification) was constructed and transfected into mice and 3T3-L1 preadipocytes at relatively low copy number. In transgenic mice the GLUT4 minigene exhibited a pattern of tissue-specific expression similar, but not identical, to that of the endogenous gene. In 3T3-L1 cells expression of minigene mRNA occurred upon differentiation into adipocytes, with kinetics virtually identical to that of endogenous GLUT4 mRNA. In both cultured adipocytes and transgenic mice, the level of expression of the minigene was low relative to that of the endogenous gene. Treatment of minigene transfected 3T3-L1 adipocytes with 8-bromo-cAMP, which represses transcription of the endogenous GLUT4 gene, also repressed expression of the GLUT4 minigene. However, insulin, which down-regulates transcription of the endogenous GLUT4 gene, failed to normally down-regulate expression of the GLUT4 minigene. These findings indicate that the cis-acting elements required for directing tissue specific expression (in heart, skeletal muscle, and brown adipose tissue), differentiation-induced activation of transcription, and cAMP-induced repression of transcription are located within the 14-kb GLUT4 minigene. However, the cis elements necessary for maximal tissue-specific expression and for insulin-induced down-regulation of expression are not located in the minigene. PMID- 8475080 TI - Signal sequence region of mitochondrial precursor proteins binds to mitochondrial import receptor. AB - An integral mitochondrial membrane protein (p32) of yeast has previously been molecularly cloned and sequenced and suggested to function as a mitochondrial import receptor. However, this protein has also been proposed to function as phosphate translocator [Guerin, B., Bukusoglu, C., Rakotomanana, F. & Wohlrab, H. (1990) J. Biol. Chem. 265, 19736-19741; Phelps, A., Schobert, C.T. & Wohlrab, H. (1991) Biochemistry 30, 248-252]. Here we have purified p32 after expression of its gene in Escherichia coli and assayed its ability to bind to various preproteins containing signal sequences for protein translocation into mitochondria, chloroplasts, or the endoplasmic reticulum. Our data suggest that p32 contains a binding site specific for the signal sequence region of mitochondrial preproteins. These data are consistent with the previous assignment of p32 as an import receptor and are discussed with regard to the apparently conflicting assignment of this protein as phosphate translocator. PMID- 8475081 TI - Rapid kinetics of mismatch repair of heteroduplex DNA that is formed during recombination in yeast. AB - Homothallic switching of yeast mating type (MAT) genes is a highly efficient gene conversion process initiated by a double-strand break. The use of a galactose inducible HO endonuclease gene has made it possible to analyze the synchronous progression of molecular intermediates during recombination. When MATa switches to MAT alpha, a 3' single-stranded end of HO-cleaved MAT DNA invades the homologous donor, HML alpha, and initiates copying of new DNA sequences. These early steps of recombination can be detected by PCR amplification. When recombination is initiated in a strain carrying the MATa-stk T-->A base pair substitution mutation located 8 bp to the right of the HO endonuclease cleavage site, the stk mutation is frequently included in heteroduplex DNA formed between MAT and HML and undergoes mismatch correction. We have followed the kinetics of mismatch repair of the stk mutation by determining the DNA sequence of the PCR amplified early intermediates of recombination. Mismatch correction of heteroduplex DNA is quite rapid (t1/2 = 6-10 min) compared to the 60 min required to complete repair of the double-strand break. Mismatch repair occurs soon after the 3'-ended MAT-stk strand invades HML and forms heteroduplex DNA. Moreover, nearly all the correction events are restorations, in which the invading MAT-stk strand is corrected to the genotype of the resident HML donor. This rapid restoration ensures that the net result will be a gene conversion at the MAT locus. Rapid and preferential mismatch repair of heteroduplex DNA has important implications in understanding meiotic recombination. PMID- 8475082 TI - A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. AB - The mammalian Y chromosome carries the SRY gene, which determines testis formation. Here we review data on individuals who are XX but exhibit male characteristics: some have SRY; others do not. We have analyzed three families containing more than one such individual and show that these individuals lack SRY. Pedigree analysis leads to the hypothesis that they carry recessive mutations (in a gene termed Z) that allow expression of male characteristics. We propose that wild-type Z product is a negative regulator of male sex determination and is functional in wild-type females. In males, SRY product represses or otherwise negatively regulates Z and thereby allows male sex determination. This hypothesis can also explain other types of sex reversal in mammals, in particular, XY females containing SRY. Some of these individuals may have mutations at the Z locus rendering them insensitive to SRY. Recessive mutations (such as the polled mutation of goats) leading to sex reversal are known in a variety of animals and might be used to map and ultimately clone the human Z gene. PMID- 8475083 TI - The role of "indirect" recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice. AB - In vitro studies have revealed several pathways by which T cells can respond to alloantigens, including CD4+ direct responses to allogeneic class II antigens, CD8+ direct responses to allogeneic class I antigens, and CD4+ "indirect" responses to peptides of alloantigens presented in association with responder class II molecules. In vivo studies of skin graft rejection, however, have so far provided clear evidence for the contribution of only the two direct pathways and not for indirect recognition. We have used major histocompatibility complex class II-deficient mice as donors to test the role of indirect recognition in rejection of skin grafts. Class II-deficient skin was always rejected without delay by normal recipients. Removal of recipient CD8+ cells (to leave the animals dependent on CD4+ function) or depletion of recipient CD4+ cells revealed that CD4+ cells were usually involved and sometimes absolutely required in this rapid rejection. Since the donor grafts lacked class II antigens, the CD4+ cells must have recognized donor antigens presented in association with recipient class II molecules. These results therefore indicate that indirect recognition can initiate rapid skin graft rejection. PMID- 8475084 TI - The two motility systems of Myxococcus xanthus show different selective advantages on various surfaces. AB - Myxococcus xanthus, a bacterium that forms fruiting bodies, moves by gliding motility utilizing dual motility systems that differ both genetically and morphologically [system A, having at least 21 genetic loci and moving mainly single cells, and system S, having at least 10 genetic loci and moving groups (rafts) of cells] [Hodgkin, J. & Kaiser, D. (1979) Mol. Gen. Genet. 172, 177 191]. In this study, we found that A- and S-gliding-motility systems have different selective advantages on surfaces containing different concentrations of agar. We observed that colonies of A+S- cells (A-motile cells) swarmed better than A-S+ cells (S-motile cells) on relatively firm and dry surfaces (e.g., 1.5% agar). In contrast, colonies of A-S+ cells swarmed much better than A+S- cells on soft and wet surfaces (e.g., 0.3% agar). Individual A-motile cells moved at a rate of 2-4 microns/min on 1.5% agar but they barely moved on 0.3% agar (< 0.5 microns/min); in contrast S-motile cells moved 3-5 times faster on 0.3% agar than on 1.5% agar. Wild-type cells with both A- and S-motility systems were able to move well over a wide range of surfaces. These results suggest that dual motility systems enable the myxobacteria to adapt to a variety of physiological and ecological environments and show similarities in function to the dual motility systems of flagellated bacteria such as Vibrio spp. PMID- 8475085 TI - Role of nitric oxide in interleukin 2-induced corticotropin-releasing factor release from incubated hypothalami. AB - Stimulation of corticotropin-releasing factor (CRF) release from the hypothalamus by interleukin 2 (IL-2) was recently demonstrated. Cytokines induce nitric oxide synthase (NOS), an enzyme that converts L-arginine into L-citrulline and nitric oxide (NO). NO is believed to be responsible for the cytotoxic action of these agents. The constitutive form of NOS occurs in neurons in the central nervous system and NO appears to play a neurotransmitter role in cerebellar and hippocampal function. We explored the probability that IL-2 and synaptic transmitters might release CRF via NO. The effects of L-arginine, the substrate for NOS, and NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, on IL-2-induced CRF release were studied using mediobasal hypothalami (MBHs) incubated in vitro in Krebs-Ringer bicarbonate buffer. L-Arginine did not alter basal and IL-2-induced CRF release after 30 min of incubation but significantly elevated both basal and IL-2-induced CRF release when MBHs were incubated 30 min longer, presumably because the endogenous substrate had been depleted after the initial 30-min incubation period. In 30-min incubations, both carbachol, an acetylcholineomimetic drug, and norepinephrine stimulated CRF release. There was an additive effect of incubation of the MBHs in the presence of carbachol (10(-7) M) and IL-2 (10(-13) M). On the other hand, coincubation of MBHs with norepinephrine (10(-6) M) and IL-2 (10(-13) M) did not produce any additive effect. Addition of NMMA, an inhibitor of NOS, at 1 or 3 x 10(-4) M completely suppressed IL-2-induced release of CRF as well as that caused by IL-2 plus carbachol. In contrast, the release of CRF induced by norepinephrine was not blocked by 3 x 10(-4) M NMMA. The data indicate that IL-2 can activate constitutive NOS leading to increased NO release, which activates CRF release. It appears that NO is also involved in the release of CRF induced by carbachol but not by norepinephrine. PMID- 8475086 TI - Baculovirus expression of the maize mitochondrial protein URF13 confers insecticidal activity in cell cultures and larvae. AB - The URF13 protein, which is encoded by the mitochondrial gene T-urf13, is responsible for cytoplasmic male sterility and pathotoxin sensitivity in the Texas male-sterile cytoplasm (cms-T) of maize. Mitochondrial sensitivity to two host-specific fungal toxins (T toxins) is mediated by the interaction of URF13 and T toxins to form pores in the inner mitochondrial membrane. A carbamate insecticide, methomyl, mimics the effects of T toxins on isolated cms-T mitochondria. URF13 was expressed in Spodoptera frugiperda (fall army-worm) cells (Sf9) in culture and in Trichoplusia ni (cabbage looper) larvae with a baculovirus vector. In insect cells, URF13 forms oligomeric structures in the membrane and confers T toxin or methomyl sensitivity. Adding T toxin or methomyl to Sf9 cells producing URF13 causes permeabilization of plasma membranes. In addition, URF13 is toxic to insect cells grown in culture without T toxins or methomyl; even a T-toxin-insensitive mutant form of URF13 is lethal to cell cultures. Baculoviruses expressing URF13 are lethal to T. ni larvae, at times postinjection comparable to those obtained by injecting a baculovirus expressing an insect neurotoxin. This result suggests that URF13 could be useful as a biological control agent for insect pests. Our data indicate that URF13 has two independent mechanisms for toxicity, one that is mediated by T toxin and methomyl and one that is independent of these toxins. Similarly, male sterility and toxin sensitivity in cms-T maize may be due to independent mechanisms. PMID- 8475087 TI - Evidence for interstrand quadruplex formation in the dimerization of human immunodeficiency virus 1 genomic RNA. AB - Retroviruses package two homologous single-stranded RNA genomes within a gag protein-RNA complex. In mature virion particles, the two RNA strands are thought to associate primarily through direct RNA-RNA interactions, although the structural basis for this stable association is unknown. We now report that a 127 nucleotide (nt) HIV-1NL4-3 RNA fragment (positions 732-858) encompassing the 5' end of the gag gene dimerizes spontaneously under high ionic strength conditions in the absence of any protein cofactor. The HIV-1 RNA dimer is dramatically and specifically stabilized by the monovalent cation potassium. Thermal dissociation of the dimer occurs at 80 degrees C in 100 mM K+ (5 mM Mg2+) but at significantly lower temperatures in the presence of either smaller or larger monovalent cations (100 mM Li+, 40 degrees C; 100 mM Na+, 55 degrees C; 100 mM Cs+, 30 degrees C). Deletion analyses of the 3' end of the 127-nt fragment reveal that an HIV-1 RNA fragment as short as 94 nt (732-825) can dimerize spontaneously, but a further 9 base deletion of the purine-rich sequence, GGGGGAGAA from positions 817 through 825, eliminates dimerization. These experimental results support a model in which HIV-1 RNA dimerizes by forming an interstrand quadruple helix stabilized by guanine (and/or purine)-base tetrads in analogy to the well-known dimerization of telomeric DNA. We speculate that this structure may also mediate the association of genomic HIV-1 RNA in vivo, revealing how RNA itself can achieve the self recognition required for subsequent genetic recombination. PMID- 8475088 TI - Calmodulin-binding domain of recombinant erythrocyte beta-adducin. AB - Adducin is a 200-kDa heterodimeric protein of the cortical cytoskeleton of mammalian erythrocytes. Analogs are also abundant in brain and several other tissues. In vitro, adducin bundles F-actin and enhances the binding of spectrin to actin. Previous studies have established that the beta subunit of adducin binds calmodulin (CaM) in a Ca(2+)-dependent fashion with intermediate affinity (approximately 200 nM) and that this activity is destroyed by proteolysis. We have confirmed the trypsin sensitivity of CaM binding by beta-adducin and the existence of a 38- to 39-kDa protease-resistant core. Calpain I digestion generates a larger core fragment (49 kDa) that is also devoid of CaM-binding activity. Use of recombinant beta-adducin peptides generated from partial cDNA clones identified strong CaM-binding activity within the protease-sensitive domain in residues 425-461: KQQKEKTRWLNTPNTYLRVNVADEVQRNMGSPRPKTT in single letter amino acid codes. This region of the molecule is highly conserved between mouse, rat, and human and shares structural features with CaM-binding sequences in other proteins. Multiple flanking PEST sequences (sequences rich in proline, glutamic acid, serine, and threonine residues that enhance proteolytic sensitivity) may contribute to the protease sensitivity of this region. Consensus sequences for phosphorylation by cAMP-dependent kinases and by protein kinase C (or CaM-dependent kinase) are also found within or near this CaM-binding domain. Collectively, these data suggest a structural basis for the regulation of adducin by Ca(2+)-dependent CaM binding and possibly by covalent phosphorylation and calpain I-mediated proteolysis as well. PMID- 8475089 TI - Mapping cis-acting defects in promoters of transcriptionally silent DQA2, DQB2, and DOB genes. AB - Defects in promoters of the nonexpressed DQA2, DQB2, and DOB genes from the class II major histo-compatibility complex were mapped by placing Z and X boxes of these silent genes into a synthetic DRA promoter. These conserved upstream sequences confer B-cell-specific and gamma-interferon-inducible expression to the DRA gene. Since DRA promoters containing the X box from the DQA2 gene and Z boxes from DQA2, DQB2, and DOB genes were neither expressed constitutively in B cells nor inducible by gamma interferon in fibroblastic cells, these conserved upstream sequences are implicated in the transcriptional defects of these silent genes. PMID- 8475090 TI - Genetic selection for crescent formation yields mouse strain with rapidly progressive glomerulonephritis and small vessel vasculitis. AB - We have established a recombinant inbred strain of mouse named spontaneous crescentic glomerulonephritis-forming mouse/Kinjoh or SCG/Kj. Mice of this strain spontaneously develop rapidly progressive glomerulonephritis. This strain of mice was derived from (BXSB/Mp x MRL/Mp-lpr/lpr)F1 hybrid mice by brother x sister mating coupled with repeated histopathologic selection for breeding of mice whose parents had the highest frequency of crescent formation in the kidneys. In this strain of mice, nephritis appears earlier and is more rapidly progressive than in any other murine model of systemic lupus erythematosus. Histopathologically, the characteristic renal lesions in the mice of this strain express a most dramatic form of crescentic glomerulonephritis. The lesions in the kidneys show only slight fine granular immune deposits along the glomerular basement membrane associated with remarkable extraglomerular proliferation and hemorrhage in Bowman's space. Although selection was not based on vasculitis, mice of this strain also exhibit a high incidence of necrotizing vasculitis. These vascular lesions involve primarily small arteries and arterioles and many organs and tissues but spare the kidneys. Thus this form of vasculitis has been found to be correlated with the crescentic form of glomerulonephritis but not with lymphoid hyperplasia of the spleen. We conclude that, in this strain of mouse, the rapidly progressive glomerulonephritis is genetically restricted and that this genetic restriction is firmly linked to that responsible for the vasculitis. PMID- 8475092 TI - Highly sensitive object location in tissue models with linear in-phase and anti phase multi-element optical arrays in one and two dimensions. AB - Based upon previous observations of low-frequency photon diffusion waves within highly scattering tissue, this paper explores the "near-field" phenomena of such waves of approximately 10-cm wavelength with 200-MHz phase modulation equipment. Multiple-element source arrays consist of laser diode sources modulated at 180 degrees out of phase with respect to the other sources. The diffusing waves originating from the out-of-phase sources give, in the midplane, an amplitude null and a sharp phase transition. These may be observed in a highly scattering intralipid medium simulating the breast or brain (0.5% intralipid), 3-5 cm from the transmitting laser diodes. In the plane containing the array, there is a high sensitivity for a small volume of a hidden absorber (indocyanine green) deep within a highly scattering medium; 20 pmol in a volume of 70 microliters can be detected. Two-dimensional arrays consisting of four or more elements in two orthogonal planes give sensitivity on both axes similar to the one-dimensional array. Measurements show that in the presence of a light-absorbing object, the amplitude null and the interference plane becomes a curved surface which is deflected toward the heterogeneity. The degree of deflection is related to the volume and the absorption characteristics of the heterogeneity and provides detection of the heterogeneity, and thereby may provide localization information for the detection of small tumors within the human breast, or stroke volumes, aneurysms, and tumors in the human brain. PMID- 8475091 TI - Identification, by protein sequencing and gene transfection, of sgp-60 as the murine homologue of CD48. AB - We have recently described a murine lymphocyte protein, provisionally termed sgp 60, which is expressed on virtually all lymphocytes of both T- and B-cell origin. A hamster monoclonal antibody to sgp-60 can inhibit interleukin-2 (IL-2) production, IL-2-receptor expression, and T-cell proliferation, events normally observed after stimulation of T cells with an antibody to the T-cell receptor/CD3 complex or with the lectin concanavalin A. Our previous studies did not reveal the molecular nature of the sgp-60 antigen. Purification of sgp-60 and protein sequencing demonstrate that sgp-60 is identical to the CD48 antigen, a ligand for the CD2 antigen, which is also called Blast-1 in humans, BCM1 in mice, and OX-45 in rats. The identity of sgp-60 and CD48 was independently confirmed in gene transfection experiments. The anti-sgp-60 monoclonal antibody was selectively reactive with COS-7 cells transfected with a BCM1 cDNA clone but not with Kb transfected controls. The results of the present report, together with our previous functional studies, may have implications for the role of CD2 and CD48 in murine T-cell activation. PMID- 8475093 TI - Molecular evidence that the spiny mouse (Acomys) is more closely related to gerbils (Gerbillinae) than to true mice (Murinae). AB - Spiny mice of the genus Acomys traditionally have been classified as members of the Murinae, a subfamily of rodents that also includes rats and mice with which spiny mice share a complex set of morphological characters, including a unique molar pattern. The origin and evolution of this molar pattern, documented by many fossils from Southern Asia, support the hypothesis of the monophyly of Acomys and all other Murinae. This view has been challenged by immunological studies that have suggested that Acomys is as distantly related to mice (Mus) as are other subfamilies (e.g., hamsters: Cricetinae) of the muroid rodents. We present molecular evidence derived from DNA.DNA hybridization data that indicate that the spiny mouse Acomys and two African genera of Murinae, Uranomys and Lophuromys, constitute a monophyletic clade, a view that was recently suggested on the basis of dental characters. However, our DNA.DNA hybridization data also indicate that the spiny mice (Acomys) are more closely related to gerbils (Gerbillinae) than to the true mice and rats (Murinae) with which they have been classified. Because Acomys and the brush-furred mice Uranomys and Lophuromys share no derived morphological characters with the Gerbillinae, their murine morphology must have evolved by convergence, including the molar pattern previously considered to support the monophyly of the Murinae. PMID- 8475094 TI - Structure of the human 3-methyladenine DNA glycosylase gene and localization close to the 16p telomere. AB - We recently reported the presence of four genes lying between the human alpha globin gene cluster and the telomere of the short arm of chromosome 16 (16p). We now report that one of these genes encodes 3-methyladenine DNA glycosylase, an enzyme important in the repair of DNA after damage by alkylating agents. The gene comprises five exons, representation of which differs in independently isolated cDNA clones. Although the gene is widely expressed, the abundance of its mRNA is considerably higher in a colon adenocarcinoma cell line (HT29) than in other cell lines that were tested. The major positive erythroid-specific regulatory element controlling alpha-globin gene expression lies equidistant between the promoters of the alpha-globin genes and the 3-methyladenine DNA glycosylase gene. Interestingly, in contrast to the alpha-globin genes, expression of the 3 methyladenine DNA glycosylase gene is not influenced by the regulatory element in the human erythroleukemia cell line K562. PMID- 8475095 TI - Enzymatic modification of plasma low density lipoproteins in rabbits: a potential treatment for hypercholesterolemia. AB - Phospholipase A2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels. PMID- 8475096 TI - Cloning of cDNA encoding Drosophila poly(ADP-ribose) polymerase: leucine zipper in the auto-modification domain. AB - We have isolated cDNA clones for a Drosophila poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) by screening a lambda gt11 cDNA library with a Drosophila partial cDNA fragment. The Drosophila PARP probe was obtained by the polymerase chain reaction with heterologous primers deduced from conserved amino acids in the mammalian, chicken, amphibian, and fish sequences. The Drosophila PARP mRNA is 3.2 kb in length and is expressed in the early stages of development. The PARP protein of 994 amino acids contains two zinc-finger motifs and an NAD-binding motif, which are conserved among different species. Interestingly, the heptad leucine repeat in an alpha-helix was found in Drosophila PARP. Alignments of the auto-modification domains of various species showed the repeated hydrophobic amino acids on the same face of the helix that make the coiled-coil configuration in the mammalian and chicken sequences. The presence of a leucine-zipper motif in the auto-modification domain suggests that this motif might be responsible for protein-protein interaction between PARP and physiological acceptors. PARP may have novel functions, possibly involving its homo- and/or heterodimerization with other nuclear leucine-zipper proteins and its regulation by ADP-ribosylation. PMID- 8475097 TI - Synthesis of a gene for sensory rhodopsin I and its functional expression in Halobacterium halobium. AB - We have designed, synthesized, and expressed in Halobacterium halobium a gene encoding sensory rhodopsin I (SR-I). The gene has been optimized for cassette mutagenesis by incorporating 30 unique restriction sites with uniform spacing throughout the 720-bp coding region. For expression, the coding region was placed downstream of the promoter and translation initiation region of the bacterioopsin gene on a selectable vector. This construct encodes SR-I with an extended N terminus that includes the 13-amino acid leader sequence and the 8-amino acid N terminus of bacterioopsin. To obtain a SR-I- H. halobium strain for expressing the synthetic gene, we used homologous recombination to delete the chromosomal gene encoding SR-I, sopI. The deletion strain was transformed with the synthetic sopI expression vector. Using antibody directed against the C-terminal region of SR-I, we detected in transformant membranes a protein with the electrophoretic mobility expected for SR-I with a processed N-terminal extension. The synthetic gene product was functionally identical to SR-I. Its flash-induced absorption difference spectrum and photochemical reaction cycle in membrane envelope vesicles were characteristic of SR-I. The protein fully restored phototaxis responses in the deletion strain. PMID- 8475098 TI - Inhibition of gene expression by triple helix-directed DNA cross-linking at specific sites. AB - Synthetic oligodeoxynucleotides represent promising tools for gene inhibition in live systems. Triple helix-forming oligonucleotides, which bind to double stranded DNA, are of special interest since they are targeted to the gene itself rather than to its mRNA product, as in the antisense strategy. Triple helix forming oligonucleotides can be coupled to DNA-modifying agents and used to introduce modifications in the DNA target in a highly sequence-specific manner. We have recently designed psoralen-oligonucleotide conjugates, which, upon binding to double-stranded DNA sequences via triple helix formation, may be cross linked in vitro to both strands of the DNA following UV irradiation. A psoralen oligonucleotide conjugate was targeted to the promoter of the alpha subunit of the interleukin 2 receptor (IL-2R alpha) gene. The triple helix site overlaps the binding site for the transcription factor NF-kappa B, which activates transcription from the IL-2R alpha promoter. After UV irradiation, the oligonucleotide conjugate becomes cross-linked to the target site and inhibits transcription of reporter plasmids transfected in live cells. Inhibition is observed when UV-induced cross-linking occurs both in vitro (before transfection) and in vivo (after transfection). We directly demonstrate that this inhibitory effect is due to triple helix formation at the target site, since a mutant of the promoter, to which oligonucleotide binding was inhibited, was not affected by the psoralen-oligonucleotide conjugate after UV irradiation. In addition, we demonstrate that site-specific cross-linking upstream of the promoter has no effect on transcription. PMID- 8475099 TI - Oxygen regulation of nifA transcription in vitro. AB - In Rhizobium meliloti, transcription of the key nitrogen-fixation regulatory genes nifA and fixK is induced in response to microaerobiosis through the action of the FixL and FixJ proteins. These two proteins are sensor and regulator homologues, respectively, of a large family of bacterial two-component systems involved in sensing and responding to environmental changes. A soluble, truncated form of the membrane protein FixL, FixL*, has been shown to be a hemoprotein that phosphorylates and dephosphorylates FixJ in response to oxygen tension. Here we use an in vitro transcription system to prove that FixJ is a transcriptional activator of both nifA and fixK and that phosphorylation of FixJ markedly increases its activity. Phosphorylation was achieved either by preincubating FixJ with FixL* and ATP or by exposing FixJ to the inorganic phospho donor ammonium hydrogen phosphoramidate. Both FixJ and FixJ-phosphate formed heparin-resistant complexes under the assay conditions used. Lastly, we were able to show that anaerobiosis, in the presence of FixL* and ATP, greatly stimulates FixJ activity at the nifA promoter with either Escherichia coli or R. meliloti RNA polymerase. This use of atmospheric oxygen to control nifA transcription in vitro represents a reconstitution of a bacterial two-component signal transduction system in its entirety, from effector to ultimate target, by the use of purified components. PMID- 8475100 TI - Heterogeneity of the principal sigma factor in Escherichia coli: the rpoS gene product, sigma 38, is a second principal sigma factor of RNA polymerase in stationary-phase Escherichia coli. AB - The rpoS gene of Escherichia coli encodes a putative RNA polymerase sigma factor that is considered to be the central regulator of gene expression in stationary phase. The gene product (sigma 38) was overproduced using the cloned rpoS gene and purified to homogeneity. Reconstituted RNA polymerase holoenzyme (E sigma 38) was found to recognize in vitro a number of typical sigma 70-type promoters, including the lacUV5 and trp promoters. Some, however, were recognized exclusively or preferentially by E sigma 70, whereas at least one, fic, was favored by E sigma 38. Thus E. coli promoters can be classified into three groups: the first group is recognized by E sigma 70 and E sigma 38, but the second and third groups are recognized substantially by either E sigma 70 or E sigma 38 alone. In contrast to other minor sigma factors, sigma 38 shares a set of amino acid sequences common among the principal sigma factors of eubacteria and is therefore a member of the RpoD-related protein family. The intracellular level of sigma 38 was demonstrated to increase in vivo upon entry into stationary phase. These results together indicate that sigma 38 is a second principal sigma factor in stationary-phase E. coli. PMID- 8475101 TI - Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine 14 and tyrosine-15. AB - Recent evidence has suggested that human cyclin-dependent kinase 2 (CDK2) is an essential regulator of cell cycle progression through S phase. CDK2 is known to complex with at least two distinct human cyclins, E and A. The kinase activity of these complexes peaks in G1 and S phase, respectively. The vertebrate CDC2/cyclin B1 complex is an essential regulator of the onset of mitosis and is inhibited by phosphorylation of CDC2 on Thr-14 and Tyr-15. In vitro, CDC2/cyclin B1 is activated by treatment with the members of the Cdc25 family of phosphatases. We found that, like CDC2, CDK2 is also phosphorylated on Thr-14 and Tyr-15 and that treatment of cyclin A or cyclin E immunoprecipitates with bacterially expressed Cdc25M2 (the mouse homolog of human CDC25B) increased the histone H1 kinase activity of these immune complexes 5- to 10-fold. Tryptic peptide mapping demonstrated that Cdc25M2 treatment of cyclin A or cyclin B1 immune complexes resulted in the specific dephosphorylation of Thr-14 and Tyr-15 on CDK2 or CDC2, respectively. Thus, we have confirmed that Cdc25 family members comprise a class of dual-specificity phosphatases. Furthermore, our data suggest that the phosphorylation and dephosphorylation of CDKs on Thr-14 and Tyr-15 may regulate not only the G2/M transition but also other transitions in the cell cycle and that individual cdc25 family members may regulate distinct cell cycle checkpoints. PMID- 8475102 TI - Transcription factor E2F binds DNA as a heterodimer. AB - E2F is a mammalian transcription factor that appears to play an important role in cell cycle control. DNA affinity column-purified E2F from HeLa cells reproducibly exhibits multiple protein bands when analyzed by SDS/PAGE. After electrophoretic purification, electroelution, and refolding of the individual protein components, the E2F DNA binding activity of the individual proteins was poor. However, upon mixing the individual components together, a dramatic (100- to 1000-fold) increase in specific DNA binding activity was observed. The five protein bands isolated can be separated into two groups based on apparent molecular mass. Optimal reconstitution of activity requires one of the two proteins found in the group of larger molecular mass (approximately 60 kDa) and one of the three proteins in the smaller-sized group (approximately 50 kDa). The reconstituted heterodimer is identical to authentic affinity-purified E2F by three criteria: DNA-binding specificity, DNA pattern, and binding to the retinoblastoma gene product. A recently cloned protein with E2F-like activity, RBP3/E2F-1, is related to the protein components of the group of larger molecular mass, as determined by Western blot analysis and reconstitution experiments. These data suggest that E2F, like many other transcription factors, binds DNA as an oligomeric complex composed of at least two distinct proteins. PMID- 8475103 TI - VirA, the plant-signal receptor, is responsible for the Ti plasmid-specific transfer of DNA to maize by Agrobacterium. AB - Agrobacteria exhibit marked Ti (tumor-inducing)/Ri (root-inducing) plasmid specificity in their interaction with the Gramineae. In this study, we have used the technique of "agroinfection," in which Agrobacterium-mediated delivery of viral genomes into plants is detected by the development of viral disease symptoms, to identify the region of the Ti plasmid which is responsible for the major differences seen in the ability of nopaline- vs. octopine-type Ti plasmids to transfer maize streak virus (MSV) DNA to maize. Introduction of fragments of the C58 (nopaline-type) Ti plasmid into strains containing an octopine-type Ti plasmid showed that a fragment containing the nopaline-type virA locus was able to complement these normally non-agroinfectious strains to high levels of MSV DNA transfer. Octopine-type virA mutant strains that express vir genes at high levels in the absence of the plant inducing compound acetosyringone also efficiently transferred MSV DNA. These findings imply a functional difference between the virA gene products encoded by octopine- and nopaline-type Ti plasmids which has a profound effect on their ability to mediate DNA transfer to maize. PMID- 8475104 TI - Temporal regulation of cyclin A-p107 and p33cdk2 complexes binding to a human thymidine kinase promoter element important for G1-S phase transcriptional regulation. AB - The cyclins are an extensive family of proteins whose cell cycle-dependent synthesis is postulated to control multiple events during the cell cycle. The synthesis of A-type cyclins begins at the start of S phase. In mammalian cells, association with the cdc-type kinases suggests that cyclin A complexes are important for DNA replication and regulating other DNA-bound substrates required for S phase. We report here that a 25-bp promoter element previously shown to be important for the G1-S activation of the human thymidine kinase (htk) promoter in growth-stimulated cells is a cellular target of cyclin A and the p33cdk2 complexes. Though the p33cdk2 and other nuclear factor complexes exhibit constitutive binding to the htk G1-S regulatory domain, the binding activity of a cyclin A/p107 protein complex is greatly enhanced when the cells enter S phase, correlating with the increase in the tk mRNA levels and the replication of DNA. The binding activity of the cyclin A complex is maintained throughout S phase. Mutation of the DNA sequences on either half of the 25-bp protein binding site results in the loss of its ability to compete efficiently in vitro for the htk complexes, including that of cyclin A-containing complex. The loss of high affinity binding for the htk complexes also substantially reduces the S-phase regulation of the htk promoter in vivo. Our results support the hypothesis that a cyclin A complex, in association with the p33cdk2 kinase, mediates the S-phase regulated transcription of the htk promoter in growth-stimulated cells. PMID- 8475105 TI - Brain structures and life-span in primate species. AB - In haplorhine primates, when the effect of body weight is removed, brain weight is correlated with maximum recorded life-span. In this paper we have analyzed the relationships between volumes of specific brain structures and life-span. When the effect of body weight is removed, the volumes of many brain structures are significantly, positively correlated with maximum recorded life-span. However, the volumes of the medulla and most first-order sensory structures do not correlate with life-span. The cerebellum is the brain structure that best correlates with life-span. Parts of the cerebellum are particularly vulnerable to age-related loss of mass in humans. For another measure of the life cycle, female reproductive age, a similar set of brain structures is significantly, positively correlated (again with the exceptions of the medulla and most first-order sensory structures). There are some differences between the structures correlated for life-span and female reproductive age. For example, the hippocampus and lateral geniculate nucleus correlate with female reproductive age but do not correlate with life-span. In strepsirhine primates, when the effect of body weight is removed, total brain weight does not significantly correlate with either life span or female reproductive age. However, the volumes of some brain structures in strepsirhines do correlate with these life-cycle parameters. The centromedial complex of the amygdala is the only structure to correlate with life-span in both strepsirhine and haplorhine primates. This structure participates in the regulation of blood pressure and in the stress response, which may be key factors governing life-span. PMID- 8475106 TI - Platelet factor 4 binds to interleukin 8 receptors and activates neutrophils when its N terminus is modified with Glu-Leu-Arg. AB - Amino acid deletion and mutagenesis experiments have indicated that the sequences Glu-Leu-Arg (ELR) preceding the first cysteine at the N terminus of interleukin 8 (IL-8) is required for receptor binding and neutrophil activation. Platelet factor 4 (PF4) is structurally related to IL-8 (35% sequence identity) but lacks the N-terminal ELR sequence and comparable effects on neutrophils. We introduced the ELR sequence at the N terminus of PF4 and found that the modified protein was a potent neutrophil activator and attractant. On the other hand, when the ELR sequence was introduced into the corresponding positions of two other proteins related to IL-8, gamma-interferon-inducible protein IP10 and monocyte chemoattractant protein 1, neither of them acquired neutrophil-activating properties, indicating that besides ELR additional structural determinants of IL 8 and PF4 are important for binding to IL-8 receptors. The conservation of these binding determinants suggests that PF4 may have evolved from a neutrophil activating protein. PMID- 8475108 TI - Chirality of DNA supercoiling assigned by scanning force microscopy. AB - Reproducible images of pBR322 plasmid molecules have been recorded by scanning force microscopy under 1-propanol. Most of the plasmids were found in a coiled state. The supercoiled molecules of our samples look like branched or unbranched interwound superhelixes. This is consistent with available electron microscopy data on circular DNA molecules. By applying a stratigraphic analysis which takes advantage of the height information contained in the scanning force microscopy images, it is possible to assign the chirality of the local supercoiling of the individual molecules. PMID- 8475107 TI - Structure-based inhibitor design by using protein models for the development of antiparasitic agents. AB - The lack of an experimentally determined structure of a target protein frequently limits the application of structure-based drug design methods. In an effort to overcome this limitation, we have investigated the use of computer model-built structures for the identification of previously unknown inhibitors of enzymes from two major protease families, serine and cysteine proteases. We have successfully used our model-built structures to identify computationally and to confirm experimentally the activity of nonpeptidic inhibitors directed against important enzymes in the schistosome [2-(4-methoxybenzoyl)-1-naphthoic acid, Ki = 3 microM] and malaria (oxalic bis[(2-hydroxy-1-naphthylmethylene)hydrazide], IC50 = 6 microM) parasite life cycles. PMID- 8475109 TI - Proliferation, differentiation, and long-term culture of primary hippocampal neurons. AB - Primary embryonic hippocampal neurons can develop morphologically and functionally in culture but do not survive more than a few weeks. It has been reported that basic fibroblast growth factor (bFGF) promotes the survival of and neurite elongation from fetal hippocampal neurons. We report that bFGF, in a dose dependent manner, can induce the survival (50 pg to 1 ng/ml) and proliferation (10-20 ng/ml) of embryonic hippocampal progenitor neurons in vitro. In serum-free medium containing high concentrations of bFGF, neurons not only proliferated (4 day doubling time) and differentiated morphologically but also could be passaged and grown as continuous cell lines. The neuronal nature of the proliferating cells was positively established by immunostaining with several different neuron specific markers and by detailed ultrastructural analyses. The proliferative effect of bFGF was used to generate nearly pure neuronal cell cultures that can be passaged, frozen, thawed, and cultured again. Neurons have been maintained > 5 months in culture. The ability to establish long-term primary neuronal cultures offers the possibility that clonal lines of distinct neuronal cell types may be isolated from specific areas of the central nervous system. Such long-term neuronal cultures should prove valuable in studying neurons at the individual cell level and also in exploring interactions between neurons in vitro. The observed dose dependence raises the possibility that cell survival and proliferation in vivo may be influenced by different levels of bFGF. PMID- 8475110 TI - Adaptation to alcoholic fermentation in Drosophila: a parallel selection imposed by environmental ethanol and acetic acid. AB - Besides ethanol, acetic acid is produced in naturally fermenting sweet resources and is a significant environmental stress for fruit-breeding Drosophila populations and species. Although not related to the presence of an active alcohol dehydrogenase, adult acetic acid tolerance was found to correlate with ethanol tolerance when sensitive (Afrotropical) and resistant (European) natural populations of Drosophila melanogaster were compared. The same correlation was found when comparing various Drosophila species. Tolerance to acetic acid also correlated with the tolerance to longer aliphatic acids of three, four, or five carbons but did not correlate with the tolerance to inorganic acids (i.e., hydrochloric and sulfuric acids). These observations suggest that acetic acid is detoxified by the conversion of acetate into acetyl-CoA, a metabolic step also involved in ethanol detoxification. Future investigations on the adaptation of Drosophila to fermenting resources should consider selective effects of both ethanol and acetic acid. PMID- 8475111 TI - Male-specific expression of mouse sex-limited protein requires growth hormone, not testosterone. AB - Sex-limited protein (Slp), an isoform of mouse complement component C4, is expressed predominantly in liver and nearly exclusively in sexually mature males or testosterone-treated females. It is encoded by a gene (C4-Slp) whose hormonal dependence has been attributed to an androgen-responsive transcriptional enhancer introduced accidentally, alongside the C4-Slp promoter, in the guise of the 5' long terminal repeat of an ancient retrovirus. We demonstrate that the pronounced rise of C4-Slp mRNA promoted by androgens in the liver is due to nuclear factors acting at a transcriptional stage. Curiously, hypophysectomized animals of either sex fail to express the gene and are refractory to testosterone. However, gene expression at male levels is restored even more promptly by injections of growth hormone alone. Additionally, animals carrying an ubiquitously expressed human growth hormone transgene lack C4-Slp mRNA and are insensitive to testosterone treatment. That growth hormone is sufficient to induce expression in a manner independent of androgen-receptor activity is shown by the hormonal treatment of Tfm mice. These androgen receptor-defective animals lack C4-Slp mRNA, which however can be fully induced by growth hormone injections. We conclude that the sexual dimorphism of C4-Slp expression employs liver nuclear mediators distinct from those directly instructed by androgens and is brought about by the intermittent rise of growth hormone, dictated by testosterone. PMID- 8475112 TI - Antibody-mediated protection in mice with lethal intracerebral Cryptococcus neoformans infection. AB - The fungus Cryptococcus neoformans is an important opportunistic pathogen for patients with AIDS. C. neoformans infections frequently involve the brain and are often fatal. In the setting of AIDS C. neoformans infections are incurable and new treatment strategies are urgently needed. Passive administration of antibody is a potential therapeutic option for the prevention and treatment of C. neoformans. The IgG1 murine monoclonal antibody 2H1 to the capsular polysaccharide of C. neoformans was studied for its ability to modify the course of lethal intracerebral cryptococcal infection in mice. Intraperitoneal administration of antibody 2H1 resulted in small, yet significant, prolongations in the average survival of mice given intracerebral infection and reduced the number of C. neoformans colonies in brain tissue. Histopathological examination of brain tissues revealed a diffuse cryptococcal meningitis with fewer organisms in the brains of mice that received antibody 2H1 than in the control group. Thus, systemic administration of a monoclonal antibody can modify the course of lethal intracerebral C. neoformans infection in mice by prolonging survival and decreasing fungal burden in brain tissues. PMID- 8475113 TI - Reactive oxygen species and neutrophil respiratory burst cytochrome b558 are produced by kidney glomerular cells in passive Heymann nephritis. AB - Reactive oxygen species (ROS) have been implicated in the production of glomerular damage in passive Heymann nephritis (PHN), an experimental form of membranous nephropathy with neutrophil-independent proteinuria. Immunohistochemistry with monoclonal antibodies specific for cytochrome b558 (a major component of the oxidoreductase complex of the respiratory burst in stimulated neutrophilic granulocytes) showed that this enzyme is localized within visceral glomerular epithelial cells (GECs) in a dense, granular pattern in rats with PHN and proteinuria. By immunoelectron-microscopy, the cytochrome was found in membrane vesicles within the GEC and also extracellularly on the GEC membranes facing the glomerular basement membrane (GBM). By immunoblotting, cytochrome b558 was detected in highest concentration in lysates of isolated glomeruli from proteinuric rats. By contrast, only traces were found in normal glomeruli by immunohistochemistry. Depletion of complement abolished the expression of the cytochrome. Using an ultrastructural cerium-H2O2 histochemistry technique, the functional activity of the glomerular ROS-generating system was demonstrated exclusively in proteinuric PHN, where H2O2 was found in highest concentration within the GBM. These results provide evidence that in rats with PHN and proteinuria, the GECs express and externalize respiratory-burst enzymes that generate ROS in a manner similar to neutrophilic granulocytes, which could then lead to glomerular damage. PMID- 8475114 TI - Cloning and expression of heparinase I gene from Flavobacterium heparinum. AB - Heparinases, enzymes that cleave heparin and heparin sulfate, are implicated in physiological and pathological functions ranging from wound healing to tumor metastasis and are useful in deheparinization therapies. We report the cloning of the heparinase I (EC 4.2.2.7) gene from Flavobacterium heparinum using PCR. Two degenerate oligonucleotides, based on the amino acid sequences derived from tryptic peptides of purified heparinase, were used to generate a 600-bp probe by PCR amplification using Flavobacterium genomic DNA as the template. This probe was used to screen a Flavobacterium genomic DNA library in pUC18. The open reading frame of heparinase I is 1152 bp in length, encoding a precursor protein of 43.8 kDa. Eleven of the tryptic peptides (approximately 35% of the total amino acids) mapped onto the open reading frame. The amino acid sequence reveals a consensus heparin binding domain and a 21-residue leader peptide with a characteristic Ala-(Xaa)-Ala cleavage site. Recombinant heparinase was expressed in Escherichia coli as a soluble protein, using the T7 polymerase pET expression system. The recombinant heparinase cleavage of heparin was identical to that of native heparinase. PMID- 8475115 TI - Lipid modifications of G proteins: alpha subunits are palmitoylated. AB - A small number of membrane-associated proteins are reversibly and covalently modified with palmitic acid. Palmitoylation of G-protein alpha and beta subunits was assessed by metabolic labeling of subunits expressed in simian COS cells or insect Sf9 cells. The fatty acid was incorporated into all of the alpha subunits examined (alpha s, alpha o, alpha i1, alpha i2, alpha i3, alpha z, and alpha q), including those that are also myristoylated (alpha o, alpha i, and alpha z). Palmitate was released by treatment with base, suggesting attachment to the protein through a thioester or ester bond. Limited tryptic digestion of activated alpha o and alpha s resulted in release of the amino-terminal portions of the proteins and radioactive palmitate. These data are consistent with palmitoylation of the proteins near their amino termini, most likely on Cys-3. Reversible acylation of G-protein alpha subunits may provide an additional mechanism for regulation of signal transduction. PMID- 8475116 TI - Two cell-density domains within the Myxococcus xanthus fruiting body. AB - Myxococcus xanthus, one of the simplest of multicellular organisms, develops into an organized, multicellular aggregate, called a fruiting body. Examination of the internal structure of the nascent fruiting body showed it to consist of a hemispherical outer domain of densely packed and ordered cells. Inside this dense shell is an inner domain of less ordered cells at 3-fold lower cell density. Single cells move in a bidirectional stream in the outer domain, orbiting the fruiting body throughout development, whereas in the inner domain, cell movement ceases as the fruiting body matures. The fruiting body thus consists of two domains, distinguished from each other by differential cell density, cell arrangements, and cell movements. PMID- 8475117 TI - Immunoglobulin heavy chain enhancer is located near or in an initiation zone of chromosomal DNA replication. AB - In several animal viruses, enhancers have been implicated in both DNA replication and transcriptional activation. The linkage of the two mechanisms appears intimate, in that common DNA binding factors can be shared. The immunoglobulin heavy chain (Igh) intronic [heavy chain joining region (JH)-mu chain constant region (C mu)] enhancer (E mu) is required for tissue-specific transcription of Igh genes and is essential for somatic recombination of diversity (D) and J segments. We show here that E mu is located at or near an origin of chromosomal DNA replication, which is more active in B lymphocytes than fibroblasts. E mu does not fulfill two criteria demonstrated for some cellular origins. E mu can initiate but not maintain autonomous replicating activity in B cells. E mu is unable to impart early replication timing to a transfected VDJ-C mu Igh locus in B cells. Instead we propose that E mu-associated ori activity contributes to tissue-specific Igh expression through local effects on chromatin structure leading to subsequent accessibility of transcription and/or recombination factors for the enhancer. PMID- 8475118 TI - Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6. AB - Pertussis toxin (PTX) is the primary component responsible for eliciting the majority of biological activities associated with Bordetella pertussis, including the induction of several tissue-adjuvant models of organ-specific autoimmune disease. PTX, when administered in vivo, enhances vascular permeability, which is made manifest by a concomitant increase in sensitivity to a variety of agents and treatments affecting the vascular bed. One such agent is histamine, and the response to PTX, as measured by hypersensitivity following vasoactive amine challenge, is genetically controlled by the Bphs locus. Susceptibility to the induction of both experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) in mice is associated with, and in the latter case linked to, a susceptible allele at this locus. We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8). This region also contains a number of loci of immunologic relevance including Igk, Ly-2, Ly-3, Il-5r, Ly-35, Ly-4, and Tnfr-2. PMID- 8475119 TI - Replacement of germ-line epsilon promoter by gene targeting alters control of immunoglobulin heavy chain class switching. AB - Recent work has shown that the ability of cytokines to direct immunoglobulin heavy chain class-switch recombination to particular heavy chain constant (C) region (CH) genes correlates with the induction of specific germ-line CH transcripts. To test the role of germ-line transcripts in class switching, we have used homologous recombination to mutate the immunoglobulin heavy chain locus of the 18.81A20 murine pre-B-cell line. In the parent cell line, the combination of interleukin-4 (IL-4) and lipopolysaccharide (LPS) induces germ-line epsilon locus transcription prior to class switching to epsilon. The heavy chain locus of the mutated cell line contains the immunoglobulin heavy chain enhancer and variable region gene promoter in place of the LPS/IL-4-responsive germ-line epsilon promoter. The mutant cell line constitutively transcribes the epsilon locus in the absence of IL-4. Strikingly, the mutant cell line also switches to epsilon in the absence of IL-4. This result demonstrates that, at least in the 18.81A20 cell line, germ-line epsilon transcription plays a direct role in class switching to the epsilon locus. In addition, the ability to change the pattern of class switching by altering transcriptional activity indicates that transcription of germ-line CH is mechanistically important in regulation of class switching. PMID- 8475120 TI - Dystrophin protects the sarcolemma from stresses developed during muscle contraction. AB - The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse. PMID- 8475121 TI - Probability model for molecular recognition in biological receptor repertoires: significance to the olfactory system. AB - A generalized phenomenological model is presented for stereospecific recognition between biological receptors and their ligands. We ask what is the distribution of binding constants psi(K) between an arbitrary ligand and members of a large receptor repertoire, such as immunoglobulins or olfactory receptors. For binding surfaces with B potential subsite and S different types of subsite configurations, the number of successful elementary interactions obeys a binomial distribution. The discrete probability function psi(K) is then derived with assumptions on alpha, the free energy contribution per elementary interaction. The functional form of psi(K) may be universal, although the parameter values could vary for different ligand types. An estimate of the parameter values of psi(K) for iodovanillin, an analog of odorants and immunological haptens, is obtained by equilibrium dialysis experiments with nonimmune antibodies. Based on a simple relationship, predicted by the model, between the size of a receptor repertoire and its average maximal affinity toward an arbitrary ligand, the size of the olfactory receptor repertoire (Nolf) is calculated as 300-1000, in very good agreement with recent molecular biological studies. A very similar estimate, Nolf = 500, is independently derived by relating a theoretical distribution of maxima for psi(K) with published human olfactory threshold variations. The present model also has implications to the question of olfactory coding and to the analysis of specific anosmias, genetic deficits in perceiving particular odorants. More generally, the proposed model provides a better understanding of ligand specificity in biological receptors and could help in understanding their evolution. PMID- 8475122 TI - Human immunoglobulin heavy-chain minilocus recombination in transgenic mice: gene segment use in mu and gamma transcripts. AB - We (N.L. and L.D.T.) have introduced a human heavy-chain minilocus into mice transgenically. Constructs contain 2 heavy-chain variable (VH; psi VH3-105 and VH5-251), 10 diversity (D), 6 heavy-chain joining (JH), and either constant (C)mu or C mu and C gamma gene segments. Several founder lines were established and studied before immunization. Seventy heavy-chain transcripts were cloned and sequenced from murine splenic B lymphocytes, and gene-segment use was assessed before and after class-switching. In general, the repertoire was "fetal" in appearance with little evidence of somatic mutation in any gene segment. The two VH gene segments were found rearranged to mu- and gamma-chain C segments, with a preference of VH5-251. We observed a preponderance of the most-J-proximal D gene (DHQ52) segments among the mu transcripts (44%). The JH gene-segment use mimics most patterns seen in human antibodies. Diversification in CDR3 was extensive and included clear examples of D inversions and D-D fusions. These data suggest that a human immunoglobulin minilocus can undergo recombinatorial processes in a manner analogous to that seen in the human fetal/preimmune repertoire. This model, in addition to providing a potential source of human monoclonal antibodies, is ideal for the study of further questions concerning immunoglobulin gene-segment recombination. PMID- 8475123 TI - Activated estrogen receptor mediates growth arrest and differentiation of a neuroblastoma cell line. AB - Several reports demonstrate estrogen receptor involvement in specific brain functions. In addition, estrogen receptors are expressed at early stages of brain development, suggesting that estrogens or related molecules may play an instructive role in the differentiation of specific brain areas. The lack of model systems in which these phenomena could be studied prompted us to develop a neuroblastoma cell line expressing the estrogen receptor. The cell line expresses the hormone receptor at levels compatible with a physiological activity. The activated estrogen receptor is capable of blocking proliferation of the cells without exerting toxic effects. Following growth arrest, the cells display a neuron-like morphology and express tau and synaptophysin, two proteins synthesized in differentiating neurons. The cell line generated will provide a valuable model system for molecular and biochemical studies of the activity of estrogens in neural-derived cells. PMID- 8475124 TI - Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. AB - We have used two-dimensional 1H NMR spectroscopy to study the conformation of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG) in solution. This is one of a series of thrombin-binding DNA aptamers with a consensus 15-base sequence that was recently isolated and shown to inhibit thrombin-catalyzed fibrin clot formation in vitro [Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. H. & Toole, J. J. (1992) Nature (London) 355, 564-566]. The oligonucleotide forms a unimolecular DNA quadruplex consisting of two G-quartets connected by two TT loops and one TGT loop. A potential T.T bp is formed between the two TT loops across the diagonal of the top G-quartet. Thus, all of the invariant bases in the consensus sequence are base-paired. This aptamer structure was determined by NMR and illustrates that this molecule forms a specific folded structure. Knowledge of this structure may be used in the further development of oligonucleotide-based thrombin inhibitors. PMID- 8475125 TI - CTX genetic element encodes a site-specific recombination system and an intestinal colonization factor. AB - In Vibrio cholerae, the genes encoding cholera toxin (ctxAB) are located on a segment of DNA (termed the "core" region) that is flanked by two or more copies of a repeated sequence called RS1. Together these DNA units comprise the CTX genetic element. Evidence presented here suggests that RS1 sequences encode a site-specific recombination system, which allows integration of a suicide plasmid carrying RS1 into an 18-base-pair sequence (attRS1) located on the chromosome of nontoxigenic V. cholerae strains. Strains of V. cholerae with large deletions removing attRS1 and the entire CTX genetic element no longer undergo site specific recombination with the RS1 sequence. Additionally, these deletion strains show a defect in intestinal colonization. Recombination experiments localize the gene responsible for enhancing colonization to a portion of the core region of the CTX element. The identified gene encodes a peptide that is highly similar in amino acid sequence to the flexible pilin of Aeromonas hydrophila. These results have important implications in the construction of stable, live attenuated cholera vaccines. PMID- 8475126 TI - Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice. AB - Lethally irradiated mice reconstituted with bone marrow expressing P210 BCR-ABL can develop myeloproliferative syndromes that resemble the initial phase of human chronic myelogenous leukemia (CML). Mice that develop the CML-like syndrome can be segregated into two groups based on the latency with which the granulocytic disease appears--early onset (< 20 weeks) and late onset (> 20 weeks). Only cells from mice exhibiting the late-onset CML-like syndrome can efficiently propagate the disease when transplanted into sublethally irradiated syngeneic recipients. Mice engrafted with late-onset murine CML cells develop a range of hematopoietic disorders that originate from multipotent stem cells. The chronic granulocytic hyperplasia can be propagated by serial transplantation into secondary and tertiary recipient mice. The majority of transplanted mice succumb to acute myeloid and B- and T-lymphoid leukemias. These data support the idea that late onset murine CML originates from a multipotent progenitor cell with a high replicating capacity. The inability to transplant the disease from mice developing the early-onset CML-like syndrome suggests that this disorder may originate from more differentiated progenitor cells with limited replication capacity that have undergone clonal expansion but are not immortalized. Although both early- and late-onset CML-like syndromes exhibit granulocytic hyperplasia, these disorders represent distinct diseases that appear to originate from different hematopoietic cell types. The late-onset CML-like disease and transfer to secondary recipients provides a useful murine model with features of the chronic and acute phases of human CML. PMID- 8475127 TI - Structure and evolutionary implications of a "cysteine-rich" Campoletis sonorensis polydnavirus gene family. AB - For successful parasitization, the female Campoletis sonorensis endoparasitic wasp injects a polydnavirus into its host, Heliothis virescens, during oviposition. Viral gene expression induces immunosuppression and alters development of the host. We report here that three abundantly expressed genes, VHv1.1, WHv1.0, and WHv1.6, describes a polydnavirus "cysteine-rich" gene family which may be important in inducing these host manifestations. These genes have a similar primary gene structure and their proteins contain cysteine motifs characteristic of snail ion-channel ligands, the omega-conotoxins. Like the omega conotoxins, the intercysteine amino acid residues are hypervariable with only three identical amino acids in all motifs. The conservation of this domain in the three viral genes may reflect an important functional role for these viral proteins in the parasitization of H. virescens. The three genes also contain introns similar in sequence at comparable positions in their 5' untranslated leaders and coding sequences. VHv1.1 contains two cysteine motifs, and each motif is interrupted by an intron at the same position as in the cysteine motifs of WHv1.0 and WHv1.6. Intron 2 sequences of WHv1.0 and WHv1.6 are 92% identical, while the immediately flanking exon sequences encoding the cysteine motifs are only 76% identical. This provides an example of nuclear pre-mRNA introns which are more conserved than flanking exons among members of a gene family. PMID- 8475128 TI - Cognition-activated low-frequency modulation of light absorption in human brain. AB - Animal model studies indicate light-absorption changes of the exposed animal brain in response to visual stimulation. Here we report observations of red-light absorbance changes, attributable to repetitive blood concentration changes in response to stimulation in the human brain frontal region by a cognitive process. These responses are observed as low-frequency recurrence of changes by Fourier transform analysis and are attributed to blood concentration change stimulated by the increased metabolic rate of brain tissue in cognitive function. A simple, portable dual wavelength spectrophotometer was attached noninvasively to the human forehead to measure the low frequency and power spectra of fluctuations of absorbances attributed to variations of brain blood concentration in the frontal region. The responses are associated with brain activity in responses to problem solving of analogies presented visually that require an associative function in the frontal region. The method of subtraction of test -rest Fourier transforms minimizes the arterial pulse frequency contributions and identifies specific frequencies--for example, 0.8, 1.6, 1.8 Hz in 24 of 28 tests of nine individuals (85%). Tests in which no increased brain activity was elicited (rest-rest) showed small differences. It is concluded that low-frequency recurrences of brain activity linked to blood concentration increases can be detected in human subjects with an optical device of potentially for simplified tests of cognitive function in the 0- to 3-Hz region and with modifications for wider band recordings in localized tissue volumes by time-resolved spectroscopy. PMID- 8475129 TI - Tetrahydrobiopterin and cytokines. AB - Biosynthesis of tetrahydrobiopterin starts from guanosine triphosphate by the action of guanosine triphosphate cyclohydrolase I, which yields the first intermediate, 7,8-dihydroneopterin triphosphate. This compound is then converted by subsequent enzymes, 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase, to tetrahydrobiopterin, the biologically active metabolite. Cytokines such as gamma-interferon or tumor necrosis factor-alpha strongly stimulate the activity of guanosine triphosphate cyclohydrolase I in murine and human cells, yielding a potentiation of intracellular tetrahydrobiopterin concentrations. In human cells, particularly in human monocytes and macrophages, the low activity of 6-pyruvoyl tetrahydropterin synthase leads to the additional accumulation of neopterin derivatives, which leak from the cells after dephosphorylation and are found increased in body fluids of humans with diseases challenging cell-mediated immunity. A functional role for the stimulation of tetrahydrobiopterin biosynthesis by cytokines is the formation of a limiting cofactor required for the enzymatic conversion of L-arginine to citrulline and nitric oxide. PMID- 8475130 TI - Persistent left ventricular dysfunction after cocaine treatment in rabbits. AB - The present study was undertaken to determine whether the diminished cardiac performance associated with cocaine administration persists after the drug has been eliminated from the body. Cocaine (5 or 10 mg/kg iv) was administered to conscious (n = 7) or pentobarbital-anesthetized (n = 7) rabbits, respectively. Seven conscious and seven anesthetized control rabbits received the saline vehicle. Two and one-half hours later, the hearts were removed from the animals and perfused under cocaine-free conditions. Left ventricular (LV) contractility was evaluated by plotting steady-state LV systolic and diastolic pressures as a function of LV end-diastolic volume (preload). LV systolic performance was diminished in a dose-related manner in hearts isolated from cocaine-treated rabbits, but was statistically different from control only at the higher cocaine dose (P < 0.05). In a second set of experiments, hearts (n = 6) were isolated, and their LV function was evaluated before, during, and after cocaine exposure. In these experiments, cocaine was added to the perfusate in increments to produce concentrations of 5, 10, and 15 mg/liter. After LV function was evaluated at the highest cocaine dose, cocaine-free perfusion conditions were restored, and LV function was reevaluated. In these experiments, cocaine produced a dose-dependent decrease in LV function that readily reversed when cocaine-free perfusion was reinstated. We conclude that cocaine diminishes LV contractility, and that the diminished cardiac performance may not readily reverse after in vivo exposure. Moreover, the rapid restoration of cardiac performance after exposure to cocaine in vitro suggests that the mechanism operating in vivo involves more than a simple direct action on the myocyte. Catecholamine cardiotoxicity does not appear to be a primary factor. PMID- 8475132 TI - Prolactin binds to human endometrial fibroblasts and inhibits mitogenicity of an endometrial carcinoma extract. AB - Uterine endometrial carcinoma has been reported to synthesize and secrete a putative peptide mitogen that elicits a potent proliferative response in endometrial fibroblasts. The extract from endometrial carcinoma stimulated [3H]thymidine incorporation into human endometrial fibroblasts in a dose dependent manner. Concomitant exposure of the fibroblasts to prolactin (PRL) led to a remarkable inhibition of the extract-stimulated mitogenic activity of the fibroblasts. This inhibition was dependent on PRL dose, and maximal effect occurred at 1 microM of PRL. PRL (10 nM) suppressed an apparent maximal activity of the extract by 50%, and the half-maximal stimulated effect of the extract on thymidine incorporation was observed at the same concentration in the absence or presence of PRL. This noncompetitive manner may imply that PRL acts at a stage after the interaction of the mitogen in the extract with the specific receptor for mitogen. When the fibroblasts were first exposed to the extract for 12 hr and then to PRL, PRL suppressed the mitogenic activity with no lag. The rapid growth inhibitory effect of PRL was mimicked by prostaglandin E1, but the combination of both types of ligand was not additive in the inhibitory action on growth. PRL and prostaglandin E1 may inhibit a similar mitogenic signaling cascade. Specific receptor sites for PRL were detected in the endometrial fibroblasts, showing high binding affinity (Kd = 16.1 nM) and low binding capacity (Bmax = 1.59 pmol/mg protein). Treatment of the fibroblasts with the endometrial carcinoma extract induced no changes in the level of PRL receptor, excluding the possibility that PRL competes for the binding sites with the mitogen. These findings would suggest that PRL may block the mitogenic activity of the fibroblasts stimulated by the endometrial carcinoma-derived mitogen via a PRL receptor-mediated mechanism, perhaps prostaglandin production. PMID- 8475131 TI - Exposure of platelet fibrinogen receptors by zinc ions: role of protein kinase C. AB - Previous studies demonstrated that Zn2+ at a concentration of 50 microM increases the number of fibrinogen receptors exposed on ADP-stimulated platelets and that higher concentrations of Zn2+ induce platelet aggregation that appears to be mediated by receptors associated with the glycoprotein IIb/IIIa complex. The purpose of this study was to identify the mechanism by which Zn2+ modulates exposure of fibrinogen receptors on the surface of human washed platelets. We determined that Zn2+ (300-800 microM)-induced platelet aggregation that was not accompanied by the release of [14C]serotonin was not blocked by ADP scavenging enzymes and 5'-p-fluorosulfonylbenzoyl-adenosine, an affinity label for ADP binding sites, but it was inhibited by disintegrins, staurosporine, and EDTA. Zn2+ (50-200 microM) showed a synergistic effect on platelet aggregation and platelet release caused by ADP and N,N,N',N'-tetrakis(2 pyridylmethyl)ethylenediamine, a Zn2+ chelator, and inhibited ADP-induced platelet aggregation that was reversed by Zn2+ (50 microM). Zn2+ (200 microM) increased the number of fibrinogen binding sites and the affinity of albolabrin (a disintegrin isolated from Trimeresurus albolabris snake venom that has been shown to bind to the fibrinogen receptor) on ADP-activated platelets. On the other hand, Zn2+ (100-800 microM) did not increase fibrinogen binding to the purified receptor. Incubation of platelets with Zn2+ (200 microM) resulted in the phosphorylation of a 47-kDa protein that was blocked by staurosporine, an inhibitor of protein kinase C. In conclusion, Zn2+ ions activate protein kinase C and enhance fibrinogen receptor exposure on the surface of platelets stimulated by ADP. PMID- 8475133 TI - Differential effects of glycosylated and nonglycosylated prolactin on islet cell division and insulin secretion. AB - A growing body of evidence suggests that prolactin (PRL) is a potent regulator of the structure and function of the islets of Langerhans, but PRL is a polymorphic hormone that exists in several molecular forms. Therefore, it is important to know whether glycosylated PRL, a major structural variant of the hormone in several species, has an effect different from that of the nonglycosylated PRL on islet function. This in vitro study examined the differential effects of glycosylated and nonglycosylated porcine PRL on cell division and insulin secretion from neonatal rat islets, and compared these results with those produced by homologous rat PRL. The nonglycosylated porcine PRL produced modest stimulation of cell division and insulin secretion from rat islets, but glycosylated porcine PRL had no significant effects. The stimulations produced by nonglycosylated porcine PRL were much weaker in comparison to those produced by the homologous rat PRL. The results show differential effects of the two structural variants of porcine PRL on rat islet function. Although these findings must be confirmed in a homologous system, the results present the possibility that the structural form of the PRL molecule available to the islet tissue may be crucial for its normal functioning. PMID- 8475134 TI - Calories, cell proliferation, and proviral expression in autoimmunity and cancer. PMID- 8475135 TI - Legionella pneumophila induced tumor necrosis factor production in permissive versus nonpermissive macrophages. AB - The ability of an opportunistic intracellular bacterial pathogen, Legionella pneumophila, to induce tumor necrosis factor (TNF) in macrophages from susceptible A/J or resistant BDF1 and BALB/c mice was determined. Cultures of peritoneal elicited macrophages from these mouse strains produced TNF in response to the Legionella. The TNF levels produced by the macrophages stimulated with either heat-killed Legionella vaccine or lipopolysaccharide were similar and dose dependent, although the amount of TNF produced by macrophages from permissive A/J mice was 2- to 4-fold higher than that produced by macrophages from the nonpermissive mice. Similar differences in TNF levels occurred when macrophages from either permissive or non-permissive mice were infected with viable Legionella. The TNF levels produced by the A/J mouse macrophages increased as a function of time after infection, with a peak of activity on Day 1 or 2, depending upon the initial concentration of the bacteria. Infection of the A/J mouse macrophages with avirulent Legionella resulted in induced levels comparable to those induced by a virulent strain. Although it is widely believed that TNF production by mouse macrophages is related to resistance to infections, the results of this study did not show a relationship between TNF production by macrophages in vitro and resistance versus susceptibility of the macrophage donor mouse strain to Legionella infection. PMID- 8475136 TI - Magnetic resonance imaging and morphometric quantitation of cartilage histology after chronic infusion of interleukin 1 in rabbit knees. AB - Cartilage pathology in rabbit knees was monitored by noninvasive magnetic resonance imaging (MRI) and evaluated using morphometric histologic measurements. Infusion of rabbit knees with the cytokine interleukin 1 induces cartilage degradation and inflammation. A miniosmotic pump was implanted subcutaneously to deliver interleukin 1 through a polyethylene catheter inserted into the rabbit knee. Rabbit knees were imaged using MRI and prepared for histologic examination at 5 and 12 days after chronic infusion of interleukin 1. MRI obtained 0.7-mm sections for three-dimensional reconstruction of cartilage image. Cartilage deterioration near the site of infusion was visible on MRI. MRI measurements indicated a reduction in cartilage thickness. Histology revealed a loss of staining of cartilage matrix proteoglycan, synovial hypertrophy, and perichondral bone resorption. Morphometric analysis of cartilage histology indicated a reduction in both cellularity (chondrocytes/m mu 2 area) and cell to matrix area ratio. These observations suggest that a loss of proteoglycan, an early event in cartilage degeneration, can be detected by MRI. PMID- 8475137 TI - Factors affecting secretory protein production in primary cultures of rat hepatocytes. AB - Previous studies suggest that protein synthesis in the liver may be influenced by alterations in hepatic proteolysis and gluconeogenesis. Since proteolysis and gluconeogenesis are accelerated in acute stress states (especially when associated with nutrient deprivation), these alterations may substantially affect hepatic protein synthesis, the integrity of which is important for host survival. In the present study, we have investigated albumin secretion and glucose production in primary cultures of rat hepatocytes in response to nutrient limiting conditions, including amino acid depletion, proteolysis inhibition, and augmented gluconeogenesis. In nonlimiting nutrient culture medium containing 10 times the normal plasma amino acid concentrations, hepatocytes produced 8.05 +/- 1.62 micrograms/plate-hr of albumin. Short-term (5 hr) inhibition of cellular protein degradation with the lysosomal protease inhibitor leupeptin did not influence albumin production, but caused a profound reduction (17-41%) when amino acid supply was reduced to the physiologic range (1.5-0.5 times, respectively). This indicates the need for active proteolysis for the maintenance of secretory protein production during nutrient limitation. Similarly, leupeptin inhibited glucose production by 22-30% at physiologic (1.5 times and 0.5 times, respectively) amino acid concentrations. Additionally, hepatocyte glucose production could be augmented 168% by epinephrine (2 microM) in 10 times medium, but this response was markedly depressed by leupeptin. Similar catecholamine mediated effects, but of a smaller magnitude, were noted at lower medium amino acid concentrations. These findings indicate that hepatocyte albumin and glucose production are associated with the common factor of active cellular proteolysis, probably through the regulation of amino acid supply. However, protein synthesis exhibits a higher priority, since stimulated hepatocyte glucose production did not substantially alter albumin secretion. PMID- 8475138 TI - Uptake and utilization of DL-5-[methyl-14C] tetrahydropteroylmonoglutamate by cultured cytotrophoblasts associated with neural tube defects. AB - A significant advance in the primary prevention of neural tube defects (NTD) is the recent finding that the periconceptional supplementation with folate has a 72% preventive effect against recurrence of NTD. However, failure of folate supplements to prevent all recurrences supports the multifactorial causation hypothesis, with inherited components exerting their influence, possibly through defects of storage, transport, or metabolism of folate. We have assessed the kinetics of DL-5-[methyl-14C]tetrahydropteroylmonoglutamate ([14C]MTHF) uptake and incorporation into the nucleic acid and protein pools by NTD-associated and control trophoblasts cultured in a medium lacking thymidine and other DNA precursors. We report a significant initial "lag" in the rate of incorporation of 14C label into the nucleic acid pool in NTD-associated trophoblasts. This we attribute to a defect in the de novo pathway of folate metabolism and its associated pathways, including the pathway for methionine synthesis, although the rate of incorporation of 14C label into the protein pool was not significantly different from that of the control cells. We discuss the possible pathways involved in the transfer of the label from the methyl group of [14C]MTHF to the nucleic acid pool, and argue that a slightly (but significantly) reduced rate of uptake into the NTD-associated cells is a reflection of the lag in incorporation into the nucleic acid pool. It is concluded that in the absence of thymidine, most of the NTD-associated trophoblasts require a longer period than controls to adjust to utilization of [14C]MTHF for synthesis of DNA, a period that could be crucial for completion of neural tube embryogenesis. We suggest that these findings could offer a way to a marker for risk of NTD. PMID- 8475139 TI - Uptake of ketone bodies in perfused hindquarter and kidney of starved, thyrotoxic, and diabetic rats. AB - To elucidate the peripheral disposal of ketone bodies in hyperketonemia accompanied with starvation, hyperthyroidism, or diabetes mellitus, the uptake of acetoacetic acid (AcAc) and beta-hydroxybutyrate (BOHB) was investigated in the perfused hindquarter and kidney of starved, thyrotoxic, and diabetic rats. Thyrotoxicity was induced by daily subcutaneous injection of thyroxine (100 micrograms/kg/day) for 7 days, and diabetes mellitus was induced by intraperitoneal streptozotocin (50 mg/kg) injection. Plasma concentration of AcAc and BOHB was significantly higher in starved, thyrotoxic, and diabetic rats than in controls. The hindquarter or kidney of rats was perfused with synthetic medium containing 0.2 or 1.5 mM AcAc or BOHB for 30 min at a flow rate of 0.5 ml/g muscle wt/min or 3.2-3.5 ml/kidney/min, respectively. In perfused hindquarter, the uptake of AcAc and BOHB was significantly reduced in starved and diabetic rats, but not in thyrotoxic rats. In perfused kidney, the uptake of AcAc and BOHB was not significantly different between the experimental and control rats. These results suggest that in starvation or diabetes mellitus, disposal of AcAc and BOHB was impaired in the hindquarter but not in the kidney, and that disposal of AcAc and BOHB by hindquarter and kidney was not impaired in thyrotoxic rats. PMID- 8475140 TI - Strain-dependent differences in vertebral bone mass, serum osteocalcin, and calcitonin in calcium-replete and -deficient mice. AB - The effects of dietary calcium intake on vertebral bone mass, composition, and turnover (calcium deposition and resorption) were determined in 10- and 14-week old C57BL/6 (small) and SENCAR (large) mice. Total vertebral mass, percent ash, calcium, magnesium, and phosphorus were higher in SENCAR mice than in C57BL/6 mice at 10 weeks of age and after being fed 0.02% or 0.6% dietary calcium for 4 additional weeks. Relative calcium deposition was higher in C57BL/6 than in SENCAR mice, while relative calcium resorption was similar in both strains. The rate of resorption was higher in mice fed 0.02% dietary calcium than in those fed 0.6% dietary calcium. Thus, C57BL/6 mice gained vertebral calcium, while it remained unchanged or declined in SENCAR mice under conditions of both calcium depletion and calcium repletion. Serum osteocalcin (an index of bone formation) was higher in C57BL/6 mice than in SENCAR mice. Mathematically significant correlations between osteocalcin levels and vertebral calcium resorption and the net vertebral calcium loss were observed only in SENCAR mice. The serum calcitonin concentration was correlated with the amount of vertebral calcium resorbed in SENCAR mice, but not in C57BL/6 mice. Thus, vertebral resorption and formation are more tightly coupled in 10- to 14-week-old SENCAR mice than in C57BL/6 mice. In addition, remodeling appears to dominate vertebral calcium dynamics in SENCAR mice, while growth dominates in C57BL/6 mice during this period. Rodents have frequently been dismissed as potential models of bone aging based on the expectation that continued growth, rather than remodeling, dominates skeletal dynamics. These data clearly demonstrate that increases in body mass ("growth") are not invariably associated with continued vertebral growth. In this murine model, both heredity and dietary calcium intake modulate vertebral bone mass, turnover dynamics, and composition at sexual maturity. These differences in the development and regulation of vertebral bone mass in small C57BL/6 and large SENCAR mice suggest that animal, as well as clinical, models provide useful insights into the cellular and hormonal mechanisms of somatotype-dependent vertebral growth. PMID- 8475141 TI - Effects of casein and soy protein on accumulation of cholesterol and dolichol in rat liver. AB - A diet containing 15% (w/w) fat and 20% (w/w) of either casein (CAS) or soy protein (SOY) was fed to 4-week-old rats for a period of 18 months. The effects of these dietary proteins on the accumulation of cholesterol and dolichol in livers were studied. After 1 month, the amount of liver cholesterol was about 5 mg/g of liver. After an additional 5 months of feeding, there was a slight decrease in cholesterol per gram of liver (3.6 mg/g of liver in CAS-fed rats and 2.6 mg/g of liver in SOY-fed rats). However, after 18 months, there were a remarkable increase (7.5 mg/g of liver) in CAS-fed rats and only a slight increase in SOY-fed rats. The proportions of liver cholesterol ester in rats fed the CAS diet were 60-70% of the total cholesterol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 70%, of cholesterol ester. The amounts of liver dolichol in rats fed the CAS and SOY diets after feeding for 18 months were 60 micrograms and 47 micrograms of liver, respectively. There was a 1.5-fold increase in both diets for a period of 18 months. The proportions of liver dolichyl fatty ester in rats fed the CAS diet were 35-40% of the total dolichol during the experimental period, but in the case of the SOY diet, only rats fed the diet for 1 month showed a high level, 36%, of dolichyl fatty ester. The proportions of dolichol ester in rats fed the SOY diet were 25-30% after 6 and 18 months of feeding. These observations indicated that the SOY diet depresses the accumulation of both liver dolichol and cholesterol. PMID- 8475142 TI - An investigation of hydrocolloids. PMID- 8475143 TI - State of the art of wound care. A survey of wound management practice in nursing homes. PMID- 8475144 TI - Tariff anomalies prevent appropriate care. PMID- 8475145 TI - A sensitive response without discrimination. Drug misuse in children and adolescents. AB - 1. Increasing numbers of children are becoming dependent on substances. 2. Although the Children Act 1989 gives children the right to refuse treatment, nurses must take steps to gain their trust and confidence. 3. Staff, working with children who misuse drugs need support and guidance. 4. Recommendations are set out which aim to enable health professionals to respect clients' confidentiality and to meet the requirements of the UKCC Code of Conduct. PMID- 8475146 TI - A positive response to an adverse reaction. Diagnosis and management of food intolerance in children. AB - 1. Food intolerance is a reproducible abnormal reaction to food or food components which is not psychologically based. 2. It is straightforward to identify immediate hypersensitivity, but delayed reactions (4-27 hours) are more difficult. 3. The main foods causing reactions are wheat, milk, chicken, eggs, fish and shellfish, but any food can cause a reaction in a sensitised individual. 4. The solution to the problem relies on identification of the causative food(s) and its total elimination from the diet. PMID- 8475147 TI - Are we meeting clients' needs? Nursing audit in continence care. AB - 1. It is becoming increasingly more important to measure processes and outcomes of care. 2. Clients' needs, expectations and satisfaction should be measured as part of continence care. 3. Locally developed tools produce a high level of enthusiasm and commitment. PMID- 8475148 TI - An investigative approach. An overview of randomised controlled trials of alternating pressure supports. AB - 1. Large-celled alternating pressure mattresses are more effective than small celled mattresses in preventing pressure necrosis. 2. Mattresses must be sufficiently robust not to break down in use. 3. Clinical trials are often faulty and therefore need to be read carefully. 4. Control regimens must be fully described. PMID- 8475149 TI - How do we keep in time? Understanding human circadian rhythms. AB - 1. Circadian rhythms tend to have a periodicity of 20-28 hours. Physiological variables such as body temperature, blood pressure, and intraocular pressure show fluctuations over each 24-hour period. 2. Circadian rhythms have an endogenous component produced by a 'clock' inside the body, and an exogenous component produced by our rhythmic lifestyle and environment. 3. An understanding of circadian rhythmicity is relevant to nurses, as variations in physiological parameters may have implications for patient care and treatment. 4. Discussion of circadian rhythmicity and its implications should be included in Project 2000 courses to increase understanding of how we 'keep time'. PMID- 8475150 TI - Osteopathy--an aid to the healing process. AB - 1. Osteopaths deal primarily with the dysfunction of joints and the resulting effects. 2. Osteopaths believe that the body is able to heal itself and that their role is to aid this process. 3. Spinal dysfunction has wide-ranging effects on all bodily systems. 4. Osteopaths use a wide variety of techniques, not just supposedly painful manipulations, and treat both spinal and non-spinal problems. PMID- 8475151 TI - A drama of growth and recognition. Drama in therapy with abused children. AB - 1. Psychodrama is a form of psychotherapy which uses drama as its main medium. 2. It has four main stages: warm-up, action, sharing and re-integration. Each stage has therapeutic elements in its own right. 3. Psychodrama is adaptable to a variety of settings and situations. 4. It has various forms, such as sociodrama and monodrama, and is separate from drama therapy, which centres on metaphor and its relationship with drama, although the two can often be used in partnership. PMID- 8475152 TI - An open approach to a delicate subject: management of diabetes-related sexual problems. AB - 1. Diabetes nurse specialists need to help people with diabetes towards better sexual health. 2. Management of a change in practice takes time, and nurses need support and encouragement to effect this. 3. A survey was devised to encourage nurses to identify their feelings about diabetes-related impotence. 4. An open approach is required to enable people with diabetes to speak freely about their impotence. PMID- 8475153 TI - A bridge from hospital to home. The role of the community liaison neonatal nurse. AB - 1. Community liaison neonatal nurses (CLNN) play an invaluable role in preparing parents for the early discharge of preterm babies. 2. The CLNN role enables babies to be discharged who would normally remain in hospital for months. 3. Preterm babies generally thrive at home, gaining weight and receiving the necessary stimuli for development. 4. CLNNs can help relieve parent anxiety and stress as well as avoid high hospital readmission rates. PMID- 8475154 TI - Reap the benefits of a cooperative approach. Understanding interdisciplinary teamwork. AB - 1. For a variety of people, teamwork is effective for nursing interaction. 2. Teamwork can benefit patients and staff if careful planning of team policies is undertaken. 3. Teamwork requires agreed values, aims and objectives together with commitment of members. 4. Lack of commitment to teamwork reduces quality care, is wasteful of resources and contradicts the UKCC Code of Professional Conduct. PMID- 8475155 TI - Private grief but a shared experience. PMID- 8475156 TI - [Synthesis and biological activity of 1,5-diaryl-3-alkylamino-4-carboxymethyl-2,5 dihydropyrrol-2-ones and 1,5-diaryl-4-carboxymethyltetrahydropyrrol-2,3-diones]. AB - By interaction of alpha-ketoglutaric acid with Schiff bases 1,5-diaryl-3 arylamino-4-carboxymethyl-2,5-dihydropyrrol-2-ones 1 were obtained. Hydrolysis of the latter, carried out with hydrochloride acid gave 1,5-diaryl-3-hydroxy-4 carboxymethyl-2,5-dihydropyrrol-2-ones 2. On treatment of 2 with aryl-amines the starting compounds 1 were yielded. All compounds were tested for their antiphlogistic activity. PMID- 8475157 TI - Hypolipidemic activity of 1-acyl- and 1,2-diacyl-3,5-pyrazolidinediones. AB - A series of substituted 1-acyl- and 1,2-diacyl-3,5-pyrazolidinediones were found to have hypolipidemic properties lowering both serum cholesterol and triglyceride levels in rodents. For optimal activity of the pyrazolidinediones, both nitrogen atoms of the ring needed to be substituted preferentially with MeCO groups. This compound lowered rat VLDL but did not elevate HDL cholesterol content. PMID- 8475158 TI - White beeswax microspheres: a comparative in vitro evaluation of cumulative release of the anticancer agents fluorouracil and ftorafur. AB - White beeswax microspheres were investigated as a vehicle for the controlled release of anticancer agents. The in vitro diffusion of fluorouracil (1) and its prodrug ftorafur (2) was studied. The transfer rate constants from simulated gastro-intestinal juices to simulated plasma, throughout artificial wall lipid membranes, were defined. The constant's values suggested that the two drugs are poorly absorbed from stomach and main absorption occurred in the intestinal tract. Microspheres of 1 and 2 were prepared by a meltable dispersion of white beeswax and a wetting agent. The method is simple, inexpensive, rapid and reproducible. The drug release from the prepared microspheres was evaluated in vitro. More than 95% of the isolated microspheres were of particle size range 100 425 microns. The average drug content was 4%. Drug dissolution was greatly retarded as a result of microsphere formation. PMID- 8475159 TI - Synthesis and in vitro antimicrobial activities of some 4-acetylantipyrine N2-(3 substituted-4-phenylthiazoline-2-ylidene)hydrazone derivatives. PMID- 8475160 TI - Photooxygenation of some potentially skin-photosensitizing hydroxyfurocoumarins. Part 2: Xanthotoxol and bergaptol. PMID- 8475161 TI - [Determination of hydroxyprogesterone caproate in serum with HPLC]. PMID- 8475162 TI - [Acute toxicity in the "yeast test" of thalidomide, taglutimide and supidimide]. PMID- 8475163 TI - [The combination of epirubicin with d-verapamil and/or tamoxifen in cell cultures]. PMID- 8475164 TI - Study of local anaesthetics. Part 101: Correlation between k' and values of surface and infiltration anaesthesia activity. PMID- 8475165 TI - Hydroxyproline content in chick embryos following the intraamniotical injection of ibuprofen. PMID- 8475166 TI - Pharmacological actions of a new procyanidin polymer from Pistacia lentiscus L. PMID- 8475167 TI - Reactions of 5-aryl-furan-2,3-diones with acylmethylenetriphenylphosphoranes: synthesis and biological activity of 3(2H)-furanone derivatives. AB - The Wittig reaction of 5-aryl-furan-2,3-diones 1 with acylmethylenetriphenylphosphoranes 2 conducted by heating under reflux in benzene solutions, proceeded regiospecifically to afford 2-acylmethylene-5-aryl-3(2H) furanones 5 in good yields. When the starting compounds 1 and 2 were allowed to react at room temperature, the stable intermediate 5-aryl-2-hydroxy-2 triphenylphosphoranylidenemethyl-3(2H)-furanone s 15 were yielded. The latter adducts underwent triphenylphosphine oxide elimination on heating to form the same olefins 5. The structural assignments of the synthesized compounds were made on the basis of their spectral data and X-ray analysis for 5a. Some of the compounds obtained exhibit antimicrobial activity and one compound of the 3(2H) furanone series exhibited anticonvulsant activity. PMID- 8475168 TI - Vascular derived growth factors: cell biology, pathophysiology, and pharmacology. PMID- 8475169 TI - Caffeine as an analgesic adjuvant: a review of pharmacology and mechanisms of action. PMID- 8475170 TI - Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical pharmacology. PMID- 8475171 TI - Modulation and dynamics of phase properties in phospholipid mixtures detected by Laurdan fluorescence. AB - Steady-state and dynamic fluorescence properties of 6-lauroyl-2 dimethylaminonaphthalene (Laurdan) have been used to ascertain the coexistence of separate phase domains and their dynamic properties in phospholipid vesicles composed of different mole ratios of dilauroyl- and dipalmitoyl phosphatidylcholine (DLPC and DPPC, respectively). The recently introduced generalized polarization together with time-resolved emission spectra have been utilized for detecting changes. The results indicate the coexistence of phospholipid phase domains in vesicle compositions in the range between 30 mol% and 70 mol% DPPC in DLPC. Below and above these concentrations a homogeneous phase is observed, with averaged properties. In the case of coexisting phase domains, the properties of each individual phase are largely influenced by the presence of the other phase. Implications on fluctuations between the coexisting phases and on the size and shape of domains are discussed. PMID- 8475172 TI - Use of sensitized fluorescence for the study of the exchange of subunits in protein aggregates. AB - The exchange of subunits between oligomer protein particles depends upon a cycle of dissociations and associations. To examine the dynamics of these cycles we have employed two methods based on the transfer of excitation energy between fluorochromes attached to different subunits of protein oligomers, at various temperatures and pressures. In the heterotransfer method, identical solutions independently labeled with two different fluorophores, donor D and acceptor A, are mixed. The fluorescence spectrum permits the determination of the subunit exchange by the increase in A and decrease in D fluorescence as mixed AD oligomers are formed. In the homotransfer method the aggregates are labeled with fluorescein to the extent that, ideally, each subunit carries a fluorophore. The emission is strongly depolarized because sufficiently often it takes place after a transfer to a fluorophore oriented differently from the one originally excited. Both dissociation and subunit exchange with unlabeled material result in an increase in polarization and can be independently determined by the homotransfer method. Both homo- and heterotransfer have been employed in the study of the effect of temperature on the stability of the aggregates and the relation between the rate of dissociation and the rate of exchange when dissociation of oligomers is induced by hydrostatic pressure. PMID- 8475173 TI - Fluorescence investigations of albumin from patients with familial dysalbuminemic hyperthyroxinemia. AB - Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant syndrome in which clinically euthyroid patients have elevated total thyroxine levels. These high serum thyroxine levels are traceable to altered binding of thyroxine to the patient's albumin. Albumin from FDH patients and normal volunteers have been purified. Reverse-phase and ion-exchange high performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis on the FDH-human serum albumin (HSA) samples show a single band that comigrates with normal HSA. In both protein solutions the intrinsic fluorescence, upon 280 nm excitation, is predominantly due to the single tryptophan residue. The quantum yield of this intrinsic fluorescence in the FDH-HSA solutions is, however, reduced relative to that of HSA. Furthermore, the "average" lifetime value of the tryptophan emission in the FDH-HSA sample is less than that of normal HSA, consistent with its reduced quantum yield. The binding of thyroxine to both albumins effectively quenches the tryptophan emission probably via a nonradiative energy transfer mechanism. Time-resolved data suggest that the albumin from the dysalbuminemic patients is actually an approximately equimolar mixture of normal HSA and FDH-HSA indicative of heterologous expression. Quenching of the intrinsic HSA and FDH-HSA fluorescence by serial additions of thyroxine showed enhanced quenching of FDH-HSA relative to HSA at any T4 to albumin mole ratio, therefore supporting earlier reports of increased thyroxine affinity to FDH-HSA. PMID- 8475174 TI - Lipid phases in renal brush border membranes revealed by Laurdan fluorescence. AB - Steady-state fluorescence properties of 6-dodecanoyl-2-dimethylaminonapththalene (Laurdan) have been used to determine the coexistence of separate lipid-phase domains in apical brush border membrane vesicles isolated from the rat renal cortex. The temperature dependence of generalized polarization has been utilized to quantitate the lipid phases. Finally, the effect of cholesterol enrichment on these parameters has been studied. The results indicate the coexistence of lipid phase domains in brush border membranes based on the values of the generalized polarization and assuming that the membrane state can be described by coexistence of gel and liquid crystalline state. At 37 degrees C, approximately 19-32% of the brush border membrane lipids are in the gel phase, and cholesterol enrichment causes a further concentration-dependent increase in the gel phase of brush border membrane lipids. PMID- 8475175 TI - Interaction of the peptide hormone adrenocorticotropin, ACTH(1-24), with a membrane model system: a fluorescence study. AB - The peptide hormone adrenocorticotropin and a related peptide were studied in solution and in interaction with a model system of membranes (small unilamellar vesicles of dipalmitoylphosphatidylcholine and 17% dimyristoylphosphatidylglycerol) via fluorescence spectroscopy. In aqueous solution, intramolecular distances between the fluorescent residues R(Tyr2-Trp9) = 9.2 A and R(Trp9-Tyr23) > or = 18 A were obtained, in agreement with molecular models. Interaction of the peptide with the negatively charged membrane is evident from the alteration of the Trp photophysical parameters (quantum yield, fluorescence spectra and anisotropy), with a partition constant between the lipidic and aqueous phase of Kp = 1-2 x 10(3). The existence of two populations of Trp in the membrane, which are distinctly accessed by acrylamide, was concluded from the tryptophan fluorescence quenching study; the two fractions are located near the membrane interface as inferred from its fluorescence quenching by the 5-doxylstearate and 16-doxylstearate lipophilic quenchers. This result is further supported by energy transfer experiments to the 3-(9-anthroyloxyl)stearic acid and 12-(9-anthroyloxyl)stearic acid probes. PMID- 8475176 TI - Use of Laurdan fluorescence in studying plasma membrane organization of polymorphonuclear leukocytes during the respiratory burst. AB - The changes in plasma membrane polarity of polymorphonuclear leukocytes (PMN) during the activation of the respiratory burst were investigated by measuring the steady-state fluorescence emission spectra of 2-dimethylamino(6-lauroyl) naphthalene (Laurdan), which is known to be incorporated at the hydrophobic hydrophilic interface of the bilayer, displaying spectral sensitivity to the polarity of its surroundings. Laurdan shows a marked steady-state emission blue shift in nonpolar solvents, with respect to polar solvents. Our results show a blue shift of the fluorescence emission spectra of Laurdan during activation of PMN with phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine. These results suggest that the activation of the respiratory burst of PMN is accompanied by a decrease in polarity in the hydrophobic-hydrophilic interface of the plasma membrane. PMID- 8475177 TI - Detection of radical ion intermediates in flavin-photosensitized pyrimidine dimer splitting. AB - Photosensitized splitting of cis-syn- and trans-syn-1,3-dimethyluracil dimers by 2',3',4',5'-tetraacetylriboflavin in acetonitrile containing a trace of perchloric acid was studied by laser flash photolysis. Protonation of the flavin prior to excitation resulted in excited singlet and triplet states that abstracted an electron from the dimers and yielded the protonated flavin radical (FlH2.+), which was detected by absorption spectroscopy. Electron abstraction by the excited singlet state predominated over abstraction by the triplet state. Approximately one-third to one-half of the excited states quenched by the trans syn dimer yielded FlH2.+, the balance presumably undergoing back electron transfer within the geminate radical ion pair generated by the initial electron transfer. A covalently linked dimer-flavin exhibited very inefficient flavin radical ion formation, consistent with the known low efficiency of dimer splitting in this system. These results constitute the first identification of a flavin radical ion intermediate in photosensitized pyrimidine dimer splitting. PMID- 8475178 TI - Influence of the peptide bond on the singlet molecular oxygen-mediated (O2[1 delta g]) photooxidation of histidine and methionine dipeptides. A kinetic study. AB - The dye-sensitized photooxidation of L-histidine (His) and L-methionine (Met) and their simplest dipeptides with glycine (Gly) (His-Gly, Gly-His Gly-Met) and Met methyl ester (Met-ME) mediated by singlet molecular oxygen (O2[1 delta g]) was studied. The overall rate constants in acetonitrile-H2O (kt) for O2(1 delta g) quenching were measured by time-resolved phosphorescence detection. In H2O a competitive kinetic method was employed. In both solvents the reactive rate constants (kr) were determined to discriminate between the overall and physical contributions to the quenching. The kinetic and mechanistic aspects of the interaction are discussed. For His-Gly, the peptide bond has practically no effect on the kinetics of photooxidation. For Gly-His the overall rate constant is much higher than that for His and His-Gly, in both H2O and acetonitrile-H2O. The main contribution to kt (for Gly-His) is the physical quenching of O2(1 delta g). In water the kt/kr ratio for free His and His-Gly is 1.0, reaching a value of 2.0 in the organic solvent-H2O mixture. The rates of -NH2 loss upon sensitized photooxidation in all cases parallel the trend of kr values. The main results for the His series indicate that: (1) a polar environment favors autoprotection (i.e. an increase in the contribution of physical quenching) against photodynamic effects; (2) only the rate constant for reactive interaction with O2(1 delta g) does not depend on the location of the peptide bond involving His. For Met derivatives the kt values are higher in both solvents than that for free Met.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475179 TI - The effect of mercuric ions on the excited states of DNA-intercalated ethidium bromide. AB - The first excited triplet state of DNA-intercalated ethidium bromide is produced with a quantum yield of 0.01 +/- 0.002 on irradiation at 532 nm. A difference extinction coefficient of 1.5 +/- 0.2 x 10(3) m2 mol-1 is measured for the triplet state at 380 nm. Mercuric ions quench the first excited singlet state of DNA-intercalated ethidium bromide via induced spin orbit coupling to give an increased yield of ethidium triplet states. The same mercuric ion that quenches the singlet state then quenches the triplet state, via the same mechanism, with a rate constant of ca 3.5 x 10(3) s-1. An upper limit for the rate of detachment of Hg2+ from its binding site in DNA may be fixed at ca 10(3) s-1. PMID- 8475180 TI - Spectroscopic properties of potential sensitizers for new photodynamic therapy start mechanisms via two-step excited electronic states. AB - Three substituted tetraazaporphyrins, octa-(4-tert-butylphenyl) tetrapyrazinoporphyrazine, tetra-(4-tert-butyl)phthalocyanine and tetra-(4-tert butyl)phthalocyanatomagnesium(t4-PcMg), were spectroscopically checked in solutions and liposomes with respect to suitability as potential sensitizers of a possible new start mechanism for photodynamic therapy (PDT) from a stepwise excited higher singlet state. This PDT start mechanism was recently proposed to overcome the problem of O2 (1delta2)-caused cutaneous phototoxicity in PDT. By means of absorption and fluorescence measurements as well as nonlinear absorption investigation, transient spectroscopy and lasing experiments, compound t4-PcMg was found to have the most appropriate properties: Based on a high fluorescence quantum yield (phiF1 = 0.84) and a very low crossing to the triplet (phiISC = 0.05), two higher excited states can be effectively populated both by two stepwise absorption transitions at 674nm consecutive absorption transitions at 684 and and 710 nm. Moreover, t4-PcMg incorporates into liposomes very well with spectroscopic properties similar to those in solution. PMID- 8475181 TI - Photophysical properties of 3,3'-dialkylthiacarbocyanine dyes in homogeneous solution. AB - The photophysical properties of 3,3'-dialkylthiacarbocyanine iodides and chlorides were measured in various solvents. It was found that photoisomerization and fluorescence are the major contributors to the deactivation of the excited singlet state; intersystem crossing occurs with only a very low efficiency. In ethanol, a triplet yield of 0.004 and a singlet oxygen quantum yield of 0.002 were determined. The photophysical parameters of these dyes are not substantially influenced by the length of the alkyl chain or the size of the halide counterion. The substitution of an ethyl with an octadecyl-chain only slightly hinders photoisomerization, and the replacement of the chloride with an iodide reduces only marginally the fluorescence lifetimes and fluorescence quantum yields in chloroform. A significant external heavy-atom effect is observed using dibromoethane as a solvent: triplet and singlet oxygen yields increase 7-10-fold, and the triplet lifetime decreases from 55 microseconds to 15 microseconds. PMID- 8475182 TI - Time-gated fluorescence imaging for the diagnosis of tumors in a murine model. AB - A system for time-gated fluorescence imaging was used to perform measurements on tumor-bearing mice treated with hematoporphyrin derivative (HpD). The aim of the study was to define the potential of this technique in the diagnosis of tumors by taking advantage of the long fluorescence lifetime of the exogenous dye with respect to the decay times of the natural fluorescence. After the administration of three different drug doses (5, 10 and 25 mg/kg body weight), fluorescence images were acquired at various uptake times (from 2 h to 10 d), to determine the best instrumental conditions and experimental procedure for the detection of tumors in the murine model considered. The optimal fluorescence contrast between the tumor area and the surrounding healthy tissue was found at 12 h after the administration of either 5 or 10 mg/kg HpD and was anticipated at 8 h for the highest drug dose. In this optimum condition, the tumor region could be identified even after the injection of 5 mg/kg HpD. A better fluorescence contrast was always obtained in 15 ns-delayed images with respect to synchronous ones. PMID- 8475183 TI - Involvement of drug-derived peroxides in the phototoxicity of naproxen and tiaprofenic acid. AB - Photodegradation of naproxen and tiaprofenic acid in aqueous buffered solutions leads to decarboxylated products with ethyl, 1-hydroxyethyl and/or acetyl side chains. The photomixtures obtained in the presence of oxygen were clearly more toxic to cultured hepatocytes than those obtained under anaerobic conditions. This effect was more noticeable in the case of naproxen. Based on the composition of the oxygenated photomixtures and the relative toxicity of the different photoproducts, it is possible to account for most of the observed toxicity in the case of tiaprofenic acid but not in the case of naproxen. This is explained as a result of the presence of drug-derived peroxidic species in the photomixtures and their contribution to the observed toxicity. Peroxides were determined by the peroxidase-catalyzed oxidation of dichlorodihydrofluorescein to its fluorescent analog. The amount of peroxides present in naproxen photomixtures was much higher than in the case of tiaprofenic acid. A dose-dependent depletion of intracellular glutathione was observed when hepatocytes were incubated with peroxide-containing naproxen photomixtures. This effect was prevented by the addition of catalase or N-acetylcysteine to the culture medium. PMID- 8475184 TI - The unusual UVA-dependent antiviral properties of the furoisocoumarin, coriandrin. AB - The novel furoisocoumarin, coriandrin, which was found recently to possess an interesting combination of photobiological properties, was investigated for antiviral activity in the presence and absence of UVA (long-wavelength ultraviolet radiation). In contrast to results obtained with other antiviral furocoumarins, such as 8-MOP (8-methoxypsoralen), coriandrin was much more phototoxic to the RNA-virus Sindbis virus than to the DNA-virus murine cytomegalovirus, although both viruses were substantially more sensitive to this compound than they were to 8-MOP. Human immunodeficiency virus, HIV-1, was also susceptible to coriandrin + UVA. Another unexpected finding was that viruses without membranes were completely resistant to coriandrin. This suggests that a membrane component was a target for the compound. The antiviral activity of coriadrin was profoundly inhibited by serum components in the reaction mixtures, which suggests that the compound may have a strong affinity for certain protein or lipid materials, although maximal interference was only obtained when all components of the reaction mixture, virus, coriandrin and serum, were irradiated simultaneously. Thus it appears that coriandrin has unusual antiviral properties that would not be predicted from its chemical similarity to furocoumarins. PMID- 8475185 TI - Benzo- and tetrahydrobenzo-psoralen congeners: DNA binding and photobiological properties. AB - Four new benzo- and tetrahydrobenzo-psoralens have been examined in their reversible interaction toward DNA and in their DNA-photobinding properties. These compounds were also examined for their ability to produce singlet oxygen and in vivo skin photosensitization reaction. Fluorescence and equilibrium dialysis measurements show that the complexation ability of benzoderivatives is remarkably high. Binding is less effective in the case of the tetrahydrocongeners. All compounds photoreact quite effectively to DNA. The photoadducts were obtained by enzymatic hydrolysis of drug-modified DNA and were characterized by high performance liquid chromatographic elution techniques. The 3,4 position represents the unique photoreactive site for benzopsoralens. Denaturation renaturation experiments confirm that the benzoderivatives are purely monofunctional, while the tetrahydrocongeners form interstrand cross-links, even though to a remarkably lesser extent than 8-methoxypsoralen (8-MOP). The new compounds, in the presence of long-wavelength ultraviolet radiation, are very moderately effective in forming reactive oxygen species; they are ineffective in promoting oxidation of tyrosine and 3-(3,4-dihydroxyphenyl)alanine to dopachrome and melanin. Skin photosensitizing experiments on guinea pigs indicate that benzo and tetrahydrobenzopsoralen derivatives are almost devoid of any phototoxic effects. Thus, this class of compounds appears to be interesting for the development of new, less phototoxic chemotherapeutic agents that interact with DNA better than 8-MOP. PMID- 8475186 TI - An ultraviolet radiation action spectrum for immediate pigment darkening. AB - The wavelength dependence for immediate pigment darkening (IPD) was investigated by exposing the midback skin of volunteers to a series of incremental fluences of narrow waveband radiation isolated by band-pass filters in the 310-400 nm region. The threshold IPD fluence for each waveband was determined by visual assessment of the skin responses immediately after each exposure. The action spectrum, constructed from the mean threshold fluences, was broad and extended from 320 nm to 400 nm with a peak at around 340 nm. No IPD could be evoked at 310 nm, even after erythemogenic fluences. The spectrum was similar in each of the three skin types investigated (III, IV, V). The broad nature of the action spectrum within the UVA region suggests that IPD may serve as an alternative endpoint for measuring photoprotection against these wavelengths. PMID- 8475187 TI - DNA nicking by ultraviolet radiation is enhanced in the presence of iron and of oxygen. AB - Double-stranded covalently closed circular supercoiled DNA (ccc DNA) from plasmid pUK 9 was irradiated in vitro at defined wavelengths in the UV region (290, 313 and 365 nm). The nicking was monitored by electrophoresis on agarose gels, ethidium staining and densitometric quantitation of supercoiled and relaxed moieties. At the explored wavelengths, the dose required for introducing one nick per million phosphodiester bonds diminishes with increased concentration of added ferric iron, whereas the effect of cupric iron is practically negligible. Adding metal chelators or bubbling argon prior to the irradiation results in a dramatic increase in the dose required for introducing one nick per million phosphodiester bonds. Taken together, these results seem to indicate that iron and oxygen play a role as cofactors in the UV-induced nicking of ccc DNA in vitro. PMID- 8475188 TI - Seasonal trends in erythemal and carcinogenic ultraviolet radiation at mid southern latitudes 1989-1991. AB - A network of solar carcinogenic/erythemal ultraviolet radiometers has been established in New Zealand. Daily integrated irradiances of this biologically harmful ultraviolet radiation for 1989, 1990 and 1991 are reported from radiometers located at Wellington (41 degrees S) and Christchurch (43.5 degrees S) and for 1990 and 1991 from the Auckland (37 degrees S) radiometer. Although the monitoring program has not been running sufficiently long to discern any long term changes in levels of solar ultraviolet radiation, shorter term trends are apparent, which are attributed to a seasonal cycle in levels of ozone at midlatitudes and changes in atmospheric aerosols. PMID- 8475189 TI - Determining the optimal dose of Photofrin in miniswine atherosclerotic plaque. AB - The purpose of this study was to determine the lowest dose of Photofrin (P) that would produce a 3:1 or greater ratio between atherosclerotic (AS) and control arterial walls. Aortoiliac AS was created in 24 Yucatan miniswine by a combination of balloon endothelial injury and 2% cholesterol and 15% lard diet for 7 weeks. Arteriography was then performed to demonstrate AS lesions. Following this, swine were given intravenously P in one of the following single dosages: 2.5, 1.0 or 0.5 mg/kg. Twenty-four hours later, swine were sacrificed and aortoiliac and control carotid artery segments removed and photographed with ultraviolet light to differentiate fluorescent from nonfluorescent areas. Arterial specimens were submitted for histologic analysis and chemical extraction for determination of fluorescence using a spectrofluorometer. Tissue concentration (ng/g tissue) of P from AS vessels were: Group I, 130.4 +/- 82.7; Group II, 10.0 +/- 1.2; and Group III, 9.1 +/- 0.6, respectively (P < 0.05). Ratios of P concentration in AS: control vessels were: Group I, 8.1 +/- 13.7; Group II, 1.1 +/- 0.2; and Group III, 0.9 +/- 0.1, respectively (P < 0.05). These results demonstrated that a P dose of 2.5 mg/kg provided at least a 3:1 ratio between AS: control artery wall. PMID- 8475190 TI - Molecular changes during the photooxidation of alpha-crystallin in the presence of uroporphyrin. AB - Singlet oxygen reacts preferentially with three amino acids in proteins, His, Trp and Met. In order to study the specific molecular events that result from such oxidations, calf alpha-crystallin was photooxidized in the presence of uroporphyrin and the reactions were investigated by high performance liquid chromatography peptide mapping using a photodiode array detector followed by fast atom bombardment mass spectrometry (FAB-MS). From these studies, the following conclusions can be inferred: (1) Upon photooxidation residue Met-68 of the B chain is oxidized to Met sulfoxide, whereas residue Trp-60 remains intact. (2) Two of the 16 His residues in alpha-crystallin are photooxidized with an apparent pKa of ca 7.0 (3) FAB-MS analysis suggests that residue Lys-166 close to the C terminal end of the A chain forms a cross-link with the His-7 residue close to the N-terminal end of the A chain. This may be either an inter- or intramolecular cross-link. PMID- 8475191 TI - Photon emission by bacteria challenged with phenylacetaldehyde. A possible distinction between gram-positive and gram-negative bacteria. AB - With all bacteria tested, addition of phenylacetaldehyde leads to light emission. The latter is markedly stronger with gram-negative bacteria, presumably because they possess a thinner wall and an extra external lipophilic membrane. Consistent with this explanation, the bactericidal effect of phenylacetaldehyde is also stronger with gram-negative bacteria. The spectrum of the emitted light shows maximal emission in the 500 nm region and is very similar to that observed when a protein (bovine serum albumin), free amino acids or isopropylamine reacts with phenylacetaldehyde. PMID- 8475192 TI - Laser-light induced chromosome aberrations in Chinese hamster cells. AB - Wild-type Chinese hamster cells CHO K1 and their radiosensitive mutant xrs5 were irradiated at 308 nm, using light pulses of a XeCl excimer laser with total energy fluences of 0.1 kJ/m2 to 4.08 kJ/m2. Chromosome-type and chromatid-type chromosome aberrations have been observed at pulse irradiances of 2.5 x 10(7) W/m2 and 1.7 x 10(8) W/m2, indicating that in mammalian cells DNA double-strand breaks occur already in this irradiance range. The results obtained with laser irradiation are compared with X-ray irradiation. PMID- 8475193 TI - Action spectra for the trans to cis photoisomerisation of urocanic acid in vitro and in mouse skin. AB - Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex. PMID- 8475194 TI - Endothelins: multifunctional renal peptides. PMID- 8475195 TI - Cardiovascular regulatory mechanisms in advanced age. PMID- 8475196 TI - Cognitive neuropsychiatry? PMID- 8475197 TI - A prospective study of delirium in elderly patients admitted to a psychiatric hospital. AB - Seventy consecutive elderly patients meeting the DSM-III criteria for non-alcohol delirium were examined during the acute stage and followed to four years later. The mean age of the patients at the beginning of the index admission was 74.8 +/- 6.4 years. The most common aetiologies for delirium were stroke, infections and metabolic disorders. Coexistent structural brain disease predisposing to delirium was found in 57 cases (81%). During the index admission, the cognitive dysfunction associated with delirium ameliorated significantly (mean +/- S.D. Mini Mental State Examination score 9.7 +/- 6.6 at admission and 13.9 +/- 7.2 at discharge, P < 0.001), but during the follow-up period of four years progression of the basic central nervous system disease was observed together with declining cognition and deteriorating functions of daily living. Four patients died during the index admission and 42 patients during the follow-up period. In decreased patients there was a statistically significant connection between the levels of cognitive functioning and functions of daily living at the end of the index admission and the life span after delirium. PMID- 8475198 TI - Emotional distress and fatigue in coronary heart disease: the Global Mood Scale (GMS). AB - Evidence indicates that emotional distress has a long-term impact on morbidity and mortality in patients with coronary heart disease (CHD), and that symptoms of depression, fatigue, and reduced energy may identify high-risk patients. This study was designed to: (1) devise a sound and practical measure of emotional distress in CHD patients; (2) examine the relationship between emotional distress and fatigue following CHD; and (3) examine changes in emotional distress as a function of cardiac rehabilitation. A sample of 478 men with CHD (mean age = 57.8 +/- 8.7 y) filled out questionnaires 3-6 weeks following a myocardial infarction (N = 110), bypass surgery (N = 302), or coronary angioplasty (N = 66). Statistical analyses of 56 Dutch mood terms were used to produce the 20-item Global Mood Scale (GMS) which measures negative affect (characterized by fatigue and malaise), as well as positive affect (characterized by energy and sociability), in patients with CHD. The GMS was found to be a reliable scale (alpha > 0.90; r > 0.55 over a 3-month period), and correlations with existing measures of emotional functioning and self-deception indicated its convergent and discriminant validity. Most importantly, fatigue was not related to cardiorespiratory fitness in a subset of 140 patients, but clearly was associated with negative affect. Consistent with the self-efficacy model, scores on the GMS mood scales improved significantly as a function of rehabilitation (P < 0.0001). Although symptoms of emotional distress are easily explained away by situational factors, previous research suggests that failure to recognize the clinical significance of these symptoms in CHD patients may result in the delay of much needed intervention. The current findings suggest that the GMS is a theoretically and psychometrically sound measure of emotional distress in CHD patients, and that this scale is sufficiently sensitive to assess change. PMID- 8475199 TI - Acting on delusion: a review. AB - The paper reviews the link between delusional beliefs and behaviour. The literature pertaining to the link between normal beliefs and behaviour is briefly examined, emphasizing the predominance of psychological and philosophical contributions to the topic. The psychiatric literature describing actions consequent upon delusional beliefs is then reviewed. In conclusion, those aspects of psychosis, distinct from delusional beliefs themselves, which may affect the likelihood of a given belief being acted upon, are discussed. PMID- 8475200 TI - Parasuicide: features of repetition and the implications for intervention. PMID- 8475201 TI - Parental 'affectionless control' as an antecedent to adult depression: a risk factor refined. AB - It has been well established that individuals with a history of depression report their parents as being less caring and more overprotective of them than do controls. 'Affectionless control' in childhood has thus been proposed as a risk factor for depression. Evidence is presented from a logistic regression analysis of data from a volunteer community sample that lack of care rather than over protection is the primary risk factor. No evidence for an interaction effect of low care and over-protection was found. PMID- 8475202 TI - Aetiology of anxiety and depressive disorders in an inner-city population. 1. Early adversity. AB - A survey of an inner-city population of working-class and single mothers is described and the prevalence of anxiety and depression reported using two related diagnostic schemes, Bedford College caseness and DSM-III-R. This acts as an introduction to an analysis which indicates that adverse experiences in childhood and adolescence (involving parental indifference, and sexual and physical abuse) considerably raise risk of both depression and anxiety conditions (with the exception of mild agoraphobia and simple phobia) in adult life. PMID- 8475203 TI - Aetiology of anxiety and depressive disorders in an inner-city population. 2. Comorbidity and adversity. AB - An earlier paper documented that adverse experiences in childhood and adolescence considerably raise risk of both depressive and anxiety conditions (with the exception of mild agoraphobia and simple phobia) in adult life. This paper deals with the same inner-city women with children at home. Consideration of adverse experiences throughout adulthood as a whole (excluding the period just before onset) particularly involving major prior losses suggests that rather different aetiological processes may be involved. Depression appears to be often linked to experiences of major loss in adulthood as a whole and to be particularly susceptible to shortcomings in the quality of ongoing social support. For anxiety only early adverse experiences appeared to be critical. (However, the onset of both conditions is often provoked by a severely threatening event in the most recent period--particularly 'loss' in depression, and 'danger' in anxiety.) Finally the critical role of early experience for both anxiety and depression explains to a considerable extent why they so often occur together; and social factors not studied in the present enquiry may account for some of the remaining unexplained comorbidity. PMID- 8475204 TI - Psychiatric disorders in relation to medical illness among patients of a general medical out-patient clinic. AB - In many patients clinical care in general medical settings is complicated by the presence of psychiatric disorders in addition to the presenting physical symptoms. In the present study the prevalence and type of psychiatric disorders was assessed in relation to the medical diagnostic findings in a general internal medicine out-patient clinic. The Present State Examination, a standardized psychiatric interview, was used to detect psychiatric disorders in 191 newly referred patients. Psychiatric disorders were found to be particularly prevalent among patients with medically ill-explained or unexplained symptoms. The prevalence of psychiatric disorders was 15% for patients with a medical explanation for their presenting symptom, 45% for patients with ill-explained and 38% for those with unexplained symptoms. Approximately 40% of the patients with psychiatric disorders met DSM-III-R criteria for somatization disorder or hypochondriasis, suggesting that these disorders contributed in particular to general medical out-patient referrals. PMID- 8475205 TI - An early Dutch study of deja vu experiences. AB - In 1904 and 1906, Heymans reported the results of two prospective questionnaire surveys on deja vu experiences and depersonalization in a sample of mainly students. Deja vu experiences appeared to be more frequent than episodes of depersonalization. Emotional sensitivity, unstable mood fluctuations, apathetic episodes and irregular working rhythm emerged as predisposing personality traits. With the exception of the working rhythm, these traits were more prominent among the respondents with episodes of depersonalization than among those with deja vu experiences. Heymans inferred that these findings supported his hypothesis that deja vu experiences and depersonalization both resulted from the diminishing or disappearance of a sense of familiarity due to a momentary reduction of psychological energy. A re-analysis of Heymans' data partly confirmed his findings and conclusions as to the predisposing factors. The authors conclude that his studies and his hypothesis have been hitherto undervalued and would deserve more attention. PMID- 8475206 TI - Detection of eating disorders in a small rural town: an epidemiological study. AB - The occurrence of eating disorders among 517 school girls (11 to 20 years of age) in a small rural Italian town was studied using a three-stage prospective procedure. The screening stage was aimed at defining risk and sub-risk groups. One year later, the risk group (N = 44) and a random sample of the sub-risk (N = 25) and of the screen-negative group (N = 32) were interviewed to detect cases of anorexia/bulimia nervosa. The case registers of four hospitals over a period of 3 years were investigated to detect any additional cases that may have been overlooked in the survey. A minimum point prevalence rate of 1.30% clinical anorexia nervosa, 1.30% sub-clinical anorexia nervosa and 0.87% sub-clinical bulimia nervosa was found for age 15 and above. No case of clinical bulimia nervosa was detected. For age 15 and below no clinical or sub-clinical cases were found. All cases of (sub-)clinical eating disorder initially belonged to the predefined sub-risk and risk groups. Because of the low positive predictive value of any single risk factor, this study shows that early case detection can be improved by using multiple risk indices. In this rural area the prevalence was as high as in metropolitan or urban areas. Urban-rural differences should be assessed in further studies. PMID- 8475207 TI - The ability of trainee general practitioners to identify psychological distress among their patients. AB - It is argued that a general practitioner's ability to make accurate ratings of psychological distress is partly determined by the rate at which patients emit cues that are indicative of such distress. This study addresses the behaviours of doctors which influence the rates at which patients emit such cues. Consultations were videotaped involving six General Practice Vocational Trainees, three of them poor, and three of them able identifiers of emotional illness. Consultations were selected so that each trainee was rated interviewing 4 patients with low GHQ scores, and 4 patients with high scores. Behaviours are described which lead to increased cue emission and which are also practised more frequently by able identifiers, while other behaviours reduce cue emission and are practised less frequently by them. Another set of behaviours is no more frequent among the able identifiers, but when practised by able identifiers is associated with increased cue emission by the patients, and when practised by poor identifiers with unaltered or decreased cue emission. Interviews that are 'patient-led' are associated with increased rates of cue emission, while those that are 'doctor led' are associated with lower rates. The implications of these findings for training doctors working in general medical settings are discussed. PMID- 8475208 TI - Influences upon attendance at out-patient facilities--the contribution of linear logistic modelling. AB - The research on attendance at out-patient psychiatric facilities has produced conflicting evidence that provides little guidance for the practitioner. It is suggested that inadequate data exploration could explain some of the discrepant findings. Analyses of multi-way tables using linear-logistic models were undertaken to demonstrate patterns of association that cannot be revealed through the use of simple chi-square tests on two-way contingency tables. The variables chosen for these analyses were those that have produced conflicting findings in the literature on children's attendance at child guidance facilities. PMID- 8475209 TI - Rehabilitation and staffing levels in a 'new look' hospital-hostel. AB - The present study examined the utility of a new hospital-hostel with low staffing levels. Results showed that the hostel was able to maintain 9 of the 10 initially transferred patients and has been able to provide some improvements in their quality of life. However, unlike highly staffed hospital-hostels, it was not able to decrease patients' disabilities. Implications of this are discussed in relation to staffing levels and practices. PMID- 8475210 TI - Some psychometric properties of the CAMCOG. AB - The CAMCOG, the cognitive section of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), was administered twice to 53 patients with a clinical diagnosis ranging from no dementia to severe dementia. The stability of the total CAMCOG score was high (0.97). Patients with less than moderate dementia were differentiated well by the total score and by subscales with a range of more than 8 points, except when education was low or age was higher than 78. Because performance on most (sub)scales is modified by age and education level, stratified norms are desirable. Only the Praxis subscale, and specifically performance on drawing tasks, appeared to be influenced by depression. PMID- 8475211 TI - The role of the practice nurse in the management of depression in general practice: treatment adherence to antidepressant medication. AB - This pilot study demonstrated the feasibility of providing practice nurse support as an adjunct to standard general practitioner treatment to patients with depressive disorders prescribed antidepressant medication. With respect to the measures used and pilot study objectives identified, there were no statistically significant differences between the study groups in treatment adherence to the prescription of antidepressant medication or in the incidence and severity of adverse events to medication. Large-scale randomized controlled trials are in progress to assess the effectiveness of practice nurse interventions in the management of depressive illness in general practice. PMID- 8475212 TI - The Research Unit of the Servizio di Psicologia Medica at the Institute of Psychiatry of the University of Verona, 1980-1991. PMID- 8475213 TI - A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11. AB - We report the results of a collaborative linkage study using 12 polymorphic markers (9 loci) from the long arm of chromosome 11, and 24 families multiply affected with schizophrenia and other closely related disorders. This region is of interest because several families have been reported in which balanced translocations involving 11q apparently co-segregate with psychotic illness. In addition, the dopamine D2 receptor, porphobilinogen deaminase, and tyrosinase genes map within the region studied and may be aetiologically involved in schizophrenia. We have primarily analysed genotypic data by the LOD score method using a range of single gene models. In order to minimize error due to mis specification of genetic parameters we have analysed data from markers at candidate gene loci by the non-parametric extended sib-pair method in addition to the LOD score method. Our results suggest that most of the region can be excluded from containing a gene of major effect in the aetiology of this disease. PMID- 8475214 TI - A computerized magnetic resonance imaging study of corpus callosum morphology in schizophrenia. AB - The hypothesis tested was that, in schizophrenia, corpus callosum size would be reduced, particularly in the region responsible for communication between both temporal lobes. This is supported by knowledge of: (a) anatomical homotopicity and functional specialization of fibres within the corpus callosum; (b) evidence linking structural and functional deficits of the corpus callosum and left temporal lobe with schizophrenia; and (c) that temporal lobe neuronal fibres pass through the middle region of the corpus callosum. Brain area and corpus callosum areas, widths and length were measured on mid-sagittal MRI scans using a computer outlining method. Scans from 30 schizophrenics and 44 normal subjects were compared. Mid-sagittal brain area, corpus callosum area, length and anterior widths were reduced in the schizophrenic group compared with controls. A significant area difference between schizophrenics and controls was seen in the mid-corpus callosum which communicates between the temporal lobes, including the superior temporal gyri. In schizophrenics, corpus callosum area reduction was not accounted for by brain area shrinkage alone. Differences between the two groups were accounted for by comparisons between males only. These findings support the hypothesis and the possibility that localized abnormalities of bilaterally connected brain regions might have secondary effects on their homotopically distributed fibres within the corpus callosum. PMID- 8475215 TI - Growth hormone and physiological responses to clonidine in depression. AB - Clonidine (1.3 micrograms/kg) was administered to 62 control and 55 depressed patients free of psychoactive drugs for at least 7 days and fasted overnight. Growth hormone (GH), pulse, blood pressure and sedation were measured every 15 min for 1 h before and 2 h after clonidine infusion. GH response did not differ significantly between control and depressed subjects overall or when divided by sex. The systolic hypotensive and sedative responses were blunted in depressed subjects compared with controls; these effects appeared to be secondary to residual antidepressant drugs since the differences were only significant for those depressed subjects with short drug-free intervals. No differences between depressed subjects and controls were seen in diastolic hypotensive or bradycardic responses and no differences in GH, cardiovascular or sedative responses were found between endogenous and non-endogenous depressed subjects. PMID- 8475216 TI - Memory for visuospatial patterns in Alzheimer's disease. AB - Immediate memory for visuospatial information was assessed in patients affected by Alzheimer-type dementia but with unimpaired visuo-perceptual functions. Patients were given two tasks: one was a traditional visuospatial memory task (Corsi's block tapping test), the second explored specifically immediate memory for visuospatial patterns. The experiment was conducted in two parallel groups of patients in Italy and the United States, each with its own appropriate sample of normal control subjects. Results showed a specific deficit of visual working memory in demented patients, even in a task in which control subjects achieved error-free performance. These data are interpreted in the light of the Working Memory Model, and suggest that in dementia the functions of the Visuospatial Scratchpad, unlike the functions of the verbal subsystems, may be impaired. PMID- 8475217 TI - The biology of autism. PMID- 8475218 TI - Learning and memory in monozygotic twins discordant for schizophrenia. AB - Learning and memory were assessed in 24 monozygotic (MZ) pairs of individuals discordant for schizophrenia or delusional disorder and seven normal pairs of MZ twins. On declarative memory tasks, the affected group displayed a pattern that might best be characterized as dysmnesic in that they performed significantly worse than the discordant unaffected group on story recall, paired associated learning, and visual recall of designs, but they learned over time, had relatively preserved recognition memory, and did not show profoundly accelerated rates of forgetting. Effortful, volitional retrieval from the lexicon, measured by verbal fluency, was also compromised in the affected group. On the other hand, procedural learning of the motor skill in a pursuit rotor task was relatively intact in the affected group. Comparisons of the normal group and unaffected group indicated that the latter group had very mild impairments in some aspects of episodic memory, namely, immediate and delayed recall of stories and delayed recall of designs. It is highly unlikely that the impairments observed in the affected group can be attributed to differences in genome, family environment, socioeconomic circumstance, or educational opportunity, as all of these were controlled by the twin paradigm. Rather, the impairments appear to be related to the intercession of disease. The neuropsychological profile is consistent with frontal lobe and medial temporal lobe dysfunction, as noted in this sample as well as other samples of schizophrenic singletons. Significant correlations between many measures of memory and global level of social and vocational functioning within the discordant group were also found. Thus difficulties in rapidly acquiring new information and propitiously retrieving old information may burden patients with schizophrenia in many of the transactions of everyday life. PMID- 8475219 TI - Working memory in clinical depression: an experimental study. AB - This study compared clinically depressed subjects with normal controls on a range of working memory tasks. The findings suggested the articulatory loop and visuospatial sketch pad components of working memory to be unimpaired in depression. On a range of clinical tasks likely to involve central executive function, depressed subjects showed impairment only on some tasks. PMID- 8475220 TI - Neuropsychological evidence of reductions on left frontal tests with hypnosis. AB - Individuals with high and low susceptibility to hypnosis were compared in a baseline condition and after instructions of hypnosis on tests of anterior left and right hemispheric functions--word fluency to letter categories, word fluency to semantic categories, design fluency and bilateral finger tapping dexterity. With hypnosis high susceptibles showed a reduction in word generation to letter categories, no significant change in word generation to semantic categories, an improvement in design fluency, and bilateral reductions in finger tapping dexterity. Low susceptibles showed the opposite changes except for the improvement in design fluency. These results, together with correlational results, were interpreted as evidence of central inhibitory processes, particularly of the left hemisphere, in response to instructions of hypnosis in high susceptibles. PMID- 8475221 TI - Psychoneuroendocrinology on the move. PMID- 8475222 TI - Cortisol reaction in success and failure condition in endogenous depressed patients and controls. AB - The authors studied differences in cortisol response to controllable and uncontrollable stress and its relationship to Seligman's theory of learned helplessness in hospitalized unipolar depressed patients (11 nontreated, acutely depressed; 11 treated patients) and 11 age and sex matched controls hospitalized for traumatic surgery. Control and lack of control were achieved by induction of success and failure in a simple number addition test and applied in balanced order on 2 consecutive days. Saliva cortisol samples were collected before and after the test. No group differences in baseline cortisol levels were observed. Cortisol increased after uncontrollable and decreased after controllable stress in control patients, whereas cortisol decreased after both conditions in the acutely depressed group and less so in the treated group, although they were as emotionally upset after failure as controls. Thus, the normally observed ability of the neuroendocrine system to discriminate between controllable and uncontrollable stress deteriorates with increasing severity of depression. PMID- 8475223 TI - Oral contraceptives and the dexamethasone suppression test. AB - Among other confounding factors, the influence of the intake of estrogen containing oral contraceptives on the dexamethasone suppression test (DST) results has never been specifically studied. Therefore, we performed 1 mg DSTs in 14 healthy women taking oral contraceptives and 14 age-matched women taking no oral contraceptives. Mean 0800h basal total cortisol was significantly higher among the women taking contraceptives than in the control group, whereas mean free cortisol did not significantly differ. At 1600h following DST, no significant difference existed between the two groups. Two subjects taking contraceptives and one control subject were considered DST nonsuppressors. These results confirm the powerful influence of oral contraceptives on basal total cortisol levels but suggest a lack of significant influence on DST results. PMID- 8475224 TI - Effect of chronic bromocriptine treatment on psychological profile of patients with PRL-secreting pituitary adenomas. AB - Hyperprolactinaemic patients are characterized by an altered psychological profile, positively modified by the administration of dopaminergic drugs. This would suggest that the same neurochemical disorder is responsible for both hyperprolactinaemia and abnormal psychological profile in these patients. To identify depression, anxiety, and aggressiveness, nine women affected by prolactin (PRL)-secreting pituitary adenomas were studied before and after 6 and 12 mo of bromocriptine therapy, by the use of different psychometric tests (Mean Minnesota Multiphasic Personality Inventory [MMPI], State-Trait Anxiety Inventory [STAI], and State and Trait Aggressiveness Scale [STAS]). As a group, the patients did not show any depressive, anxious, or aggressive tendencies. Furthermore, no significant modifications were observed during dopaminergic treatment. Patients bearing PRL adenomas seem to be characterized by a dopaminergic background different from that found in functional hyperprolactinaemia. This hypothesis could explain the different psychological configuration and behavior in response to the administration of dopaminergic compounds. PMID- 8475225 TI - Effect of regularity of exposure to chronic immobilization stress on the circadian pattern of pituitary adrenal hormones, growth hormone, and thyroid stimulating hormone in the adult male rat. AB - Circadian variation of serum levels of adrenocorticotropin hormone (ACTH), corticosterone, growth hormone (GH), and thyroid-stimulating hormone (TSH) were studied in three groups of adult male rats exposed to chronic intermittent immobilization stress (IMO) for 2 hr daily under different schedules. IMO resulted in reduced food intake, body weight loss, and increased adrenal weight. ACTH levels were not affected but corticosterone levels were increased in all IMO rats as compared to control ones during the diurnal phase of the circadian cycle. IMO decreased serum GH and TSH levels but the circadian pattern of secretion was influenced in a complex way depending on the specific pattern of daily exposure to IMO. Differences observed between the IMO groups were not caused by differences in food intake because its circadian rhythm was very similar in all IMO groups. These results suggest that regularity of exposure to immobilization alters in a complex fashion circadian GH and TSH rhythms. PMID- 8475226 TI - Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women. AB - The aim of this study was to analyze the effects of delta sleep-inducing peptide (DSIP) on growth hormone (GH) and prolactin (PRL) secretion in eight healthy women with normal cycles (aged 17-36 years). GH and PRL secretion was studied in five women after DSIP (25 micrograms/kg bw IV over 30 min), arginine chlorhydrate (0.5 g/kg bw IV over 30 min) and simultaneous DSIP plus arginine chlorhydrate administration. In three other women the circadian rhythm of GH and PRL was studied during DSIP (25 micrograms/kg bw from 2130h to 2230h) and placebo IV infusion. Serum GH and PRL levels were normal under basal conditions and no effects were noted after the infusion of DSIP. The GH and PRL circadian rhythm was not modified by DSIP administration. DSIP did not influence GH and PRL responsiveness to arginine chlorhydrate. We found that at dosages which are known to modify ECG patterns, DSIP is unable to modify spontaneous or arginine chlorhydrate-induced GH and PRL secretion. PMID- 8475227 TI - Perimenstrual complaints in women complaining of PMS, menorrhagia, and dysmenorrhea: toward a dismantling of the premenstrual syndrome. AB - Four groups of women were compared in terms of their perimenstrual symptoms, reported menstrual blood loss and period pain, and neuroticism scores: three patient groups were referred to a Gynaecology Outpatient Clinic because of menorrhagia (N = 101), PMS (N = 104), dysmenorrhea (N = 56), and a control group (N = 105). The three patient groups showed considerable overlap in a number of symptoms. This has led us to postulate three factors contributing to perimenstrual complaints: a) a 'timing factor' linked to the ovarian cycle; b) a 'menstruation factor,' associated with the buildup of the endometrium and its shedding; and c) a 'vulnerability factor,' one aspect of which, 'neuroticism,' was measured in this study. Depressive symptoms, which were the most important in leading women to seek help for their PMS, were related to all three factors. Depressive mood changes seemed to be linked to the 'timing factor' but were noticeably worse and more prolonged in women with high neuroticism, heavy bleeding, or severe pain. One premenstrual symptom, food craving, was of considerable interest. This was weakly related to neuroticism, not apparently affected by the 'menstruation factor' and differed in severity between those in the PMS group and the other three groups. It is potentially relevant that both carbohydrate craving and depression are linked to serotonergic changes in the brain, which may prove to be particularly marked in the late luteal phase. PMID- 8475228 TI - Case report: recurrent pseudocyesis in a male patient with psychosis, intermittent hyponatremia, and polydipsia. AB - This report describes a case of recurrent pseudocyesis in a man with psychosis, intermittent hyponatremia, and polydipsia. The pseudocyesis was documented on three separate occasions coinciding with bouts of acute hyponatremia and rapid weight gain stemming from ingestion of large amounts of water. In contrast, no pseudocyesis was elicited during intervening normonatremic states. Abdominal distention, neuropsychological deterioration, and worsening of psychosis during acute hyponatremia are considered as contributing factors to the pseudocyesis. PMID- 8475229 TI - Aerobic exercise and the placebo effect: a controlled study. AB - An experiment was conducted with 48 healthy young adults engaged in a supervised 10-week exercise program to determine whether a placebo effect is involved within the exercise-psychological enhancement connection. Based on an expectancy modification procedure, one-half of the subjects were led to believe that their program was specifically designed to improve psychological well-being (experimental condition) whereas no such intervention was made with the second half (control condition). Expectations for psychological benefits and aerobic capacity (VO2max) were measured before and after completion of the program. Self esteem, as the indicator of psychological well-being, was measured on four specific occasions: at the beginning, after the fourth and seventh weeks, and upon completion of the training program. The results showed similar significant increases in fitness levels in both conditions. Moreover, self-esteem was significantly improved over time in the experimental but not in the control condition. These findings provide evidence to support the notion that exercise may enhance psychological well-being via a strong placebo effect. Implications of the results with regard to exercise prescription are discussed. PMID- 8475230 TI - Dependence between apolipoprotein E phenotypes and temperament in children, adolescents, and young adults. AB - The association of apolipoprotein E (apoE) polymorphism with temperament and Type A behavior was studied in 1577 randomly selected healthy children, adolescents, and young adults during a follow-up period of 9 years. Temperament was correlated with apoE phenotypes. Motor activity, even hyperactivity, in childhood and mental vitality in adolescence and young adulthood increased significantly with the apoE phenotypes in the order of E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4. However, global Type A behavior was not associated with the order of apoE phenotypes. The findings suggest the importance of additional studies on genetic factor and temperament. PMID- 8475231 TI - Psychosocial factors associated with cardiovascular reactivity in older adults. AB - This study examined associations of psychosocial factors with cardiovascular reactivity in two groups of men and women--spouse caregivers of individuals with Alzheimer's disease (M age = 69.4 N = 82) and controls (M age = 68.5, N = 78) group-matched for age and gender. Cardiovascular responses to an emotional task (speech sample about one's spouse) yielded higher systolic and diastolic blood pressures (SBP, DBP) than a spoken cognitive task, which in turn yielded higher BPs and heart rate (HR) than the baseline rest period. HR was greater in response to the two tasks than in response to the baseline period, but it did not differ across tasks. Regression models of SBP, DBP, and HR reactivity in response to the two tasks demonstrated that after controlling for hypertension and gender, combinations of hostility, anger expression, avoidance coping, Type A behavior and Expressed Emotion (criticism) explained more reactivity in response to the emotional (8-12%) than the cognitive task (4-7%). Caregivers were more reactive than controls only if they were hypertensive. Psychosocial factors may be as important in explaining reactivity in older adults as in younger adults. PMID- 8475232 TI - Psychophysiological responses to exercise in type A/B men. AB - Previous research concerning physical exercise has yielded mixed results with regard to the possible influence of the Type A behavior pattern (TABP) on ratings of perceived exertion. However, almost all studies have been performed in the confined space of a laboratory. Few have studied the influence of an individual's behavior pattern outdoors in the field where most everyday exercise takes place. Hence, the present study compared three groups of subjects: one group with pronounced TABP, one showing very little TABP, and finally one intermediate group exhibiting an average level of Type A behavior. The results indicate that there are distinct and statistically significant differences between the groups. Type A individuals underestimate their degree of perceived exertion at comparable levels of heart rate. Thus, an individual's behavior pattern ought to be considered when ratings of perceived exertion are used to quantify exercise intensity. PMID- 8475233 TI - Type A behavior, tension, and ambulatory cardiovascular reactivity in workers exposed to noise stress. AB - Recent negative findings regarding differences in blood pressure (BP) and heart rate (HR) reactivity at work between Type A and Type B workers may stem from the failure to note the stressors to which they were exposed. In this naturalistic study, an objective work stressor--varying levels of ambient noise--was individually monitored among 123 normotensive males. We examined the relationship of Type A behavior (assessed by the Thurstone Temperament Schedule) to ambulatory BP and HR reactivity under high and low noise conditions. We also tested the hypothesized mediating function of tension arousal. Results of multiple regression analyses indicated that when workers were exposed to high noise levels (> or = 80 dB(A)), Type A behavior was positively related to diastolic BP (p = 0.029) and HR reactivity (p = 0.0001), even after adjusting for clinic values, time of measurement, worker activities, and body position during measurement. When the same workers were exposed to low noise levels, the results were not significant. This suggests that noise constitutes a stressor for Type A individuals, and highlights the importance of noting the actual stressor-exposure condition. In addition, Type A individuals reported high tension, noted concurrently with the ambulatory measurements. Tension arousal was also related to BP and HR reactivity. Adding the tension variable to the above regressions weakened the relationship between Type A behavior and BP and HR reactivity. Thus, the tension experienced by Type A workers exposed to noise stress may have served as a mediator of cardiovascular reactivity. PMID- 8475234 TI - Cynical hostility and cardiovascular reactivity during self-disclosure. AB - Recent research suggests that hostility might contribute to the development of coronary heart disease (CHD) and other illnesses. One potential mechanism linking hostility and health is exaggerated physiological reactivity to social stressors. Given that mistrust and suspiciousness are closely related to this trait, the self-disclosure of personal information regarding a stressful experience may elicit heightened reactivity in hostile persons. To evaluate this hypothesis, undergraduate men (N = 60) classified as high or low on the Cook and Medley Hostility (Ho) Scale were randomly assigned to either a self-disclosure or a nondisclosure condition. Consistent with prediction, among subjects participating in the self-disclosure discussion task, hostile individuals displayed significantly greater blood pressure reactivity compared with subjects low in hostility. These results support the psychophysiological reactivity model of hostility and health, and underscore the potential importance of social context in the psychosomatic process. PMID- 8475235 TI - Hostility and differences between clinic, self-determined, and ambulatory blood pressure. AB - This study examined the role of personality factors in differences between three methods of assessing blood pressure (clinic, self, ambulatory) in 45 patients with mild hypertension. The data were obtained after the patients were withdrawn from antihypertensive medications and had achieved stable clinic diastolic blood pressure levels of 95 to 110 mm Hg, averaged over three visits in 2 to 4 weeks. Significant differences were obtained in systolic blood pressure (SBP) and diastolic blood pressure (DBP) as a function of method of assessment. These differences in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were associated with individual differences in the total score and several subscales of the Buss-Durkee Hostility Inventory (Assault, Resentment, Guilt), but not in anxiety, depression, or other characteristics. High hostile subjects had consistently high blood pressure values in both clinic, self, and ambulatory recordings. Low hostile subjects were significantly lower in self-recorded blood pressure readings taken at home and in ambulatory recordings, compared with clinic values. Implications of these findings for "white coat hypertension" are discussed. PMID- 8475236 TI - Psychiatric education improves internists' knowledge: a three-year randomized, controlled evaluation. AB - Trainees were randomized into four groups: (1) control; (2) consult; (3) liaison; or (4) consult-plus-liaison to evaluate the psychiatric knowledge gained after two different training programs for primary care residents. Consult was a 1-month rotation on the Psychiatry Consultation Service. Liaison consisted of 31-hour workshops over 1 year. Consult-plus-Liaison refers to both training programs, experienced in consecutive years. An oral examination was administered before and after training. The analysis of variance and tests of simple effects revealed significant training effects for both groups. The effect size of training was greater for residents exposed to both programs, compared with either one alone. The two different training programs were both effective in improving the psychiatric knowledge of primary care residents and exposure to both programs proved superior to either one alone. PMID- 8475237 TI - Psychiatric symptoms in systemic lupus erythematosus: an update. AB - Twenty-one studies on the prevalence and type of psychiatric symptoms in systemic lupus erythematosus (SLE) are reviewed and evaluated. Substantial differences in prevalence of psychiatric symptoms in SLE-patients (from 17%-71%) have been reported. Of the investigated methodological aspects, differences in assessment techniques appeared to be the main source of the variability in findings. Although various types of psychiatric symptoms have been observed, depression is most frequently reported. There was no consistent relationship between the occurrence of psychiatric symptoms and other symptoms of SLE. However, the data suggest an association with (the patient's perception of) illness severity and with the experience of psychosocial stressors. Studies applying control groups (patients with other chronic diseases (e.g., rheumatoid arthritis) showed striking similarities between both patient groups with respect to prevalence and type of psychiatric symptoms. There is some evidence, however, indicating that a small proportion of the psychiatric symptomatology, in particular psychosis, is related to neurological dysfunction in SLE. PMID- 8475238 TI - Quality standards in the NHS. PMID- 8475239 TI - Orthoptic screening for three- and four-year-olds. PMID- 8475240 TI - Measles outbreak in Fife: which MMR policy? AB - The introduction of measles, mumps and rubella vaccine (MMR) into the United Kingdom childhood immunisation schedule has resulted in a substantial reduction in the incidence of all three diseases. None the less, there have recently been outbreaks of measles in parts of the country which have a record of high MMR uptake among young children. In these outbreaks it is mainly older children who have been affected. This report documents such an outbreak in Fife, an area with a very high MMR uptake among two-year-old children (96%). The current policy of giving MMR vaccine only once to children at 15 months of age may not be sufficient to enable the United Kingdom to achieve the WHO target of measles elimination by the year 2000. Other possible strategies to achieve this objective are discussed. PMID- 8475241 TI - Guidelines for local research ethics committees: distinguishing between patient and population research in the Multicentre Research Project. AB - A multicentre population research study was undertaken, involving ethical approval from 28 local research ethics committees. The major problems encountered were delays, which fell into three categories: requests to complete separate application forms, delay in processing applications and additional requests for patient and consultant consent. We examine these sources of delay in the context of the recently published DoH guidelines for local research ethics committees. Our findings reveal that there is not only an absence of adequate guidelines for multicentre research studies but that the new guidelines for local research ethics committees fail to distinguish between patient research and the population study. PMID- 8475242 TI - Car occupant restraint use in Fife: an observational study. AB - Today road traffic accidents pose a major public health problem with a significant number of deaths and injuries among drivers and passengers of all ages. As part of road safety strategy in Fife the Health Board and Regional Council have carried out an observational study of 7,885 occupants in 4,292 cars to determine the extent of appropriate restraint use in the region. Overall restraint use for urban and non-urban sites was found to be 80%. In car drivers restraint use was 94%. Passengers in all rear seat positions were observed to have a significantly lower level of restraint use, 33% overall compared with 92% overall in the front (chi 2 2,827.9, P << 0.001), with usage of restraint declining with increasing age. Particular problems noted were: the much lower use of restraint among children travelling to and from school, the use of restraint inappropriate to children's age, and the significantly lower level of restraint among taxi drivers and their passengers compared with other cars (chi 2 114.9, P << 0.001). These findings have implications for the promotion of restraint use for all car occupants. PMID- 8475243 TI - Routine or selective school entry medicals: a review of current literature. AB - A review of recent literature on school entry medicals (SEMs) assessed whether selective medicals were as effective and/or cheaper than routine medicals. Data were compared with prospective data from the author's 'patch' on a one-year cohort of routine SEMs. Routine medicals showed that 40-50% of school entrants had health problems but selective systems detected fewer. Districts with high morbidity were less able to detect problems early but effective child health surveillance was not related to the number of new problems at SEM. Selection did not reduce costs and could increase costs in deprived areas. The SEM is an opportunity for health education which is valued by parents. On present evidence, selection for medicals at school entry cannot be recommended. PMID- 8475244 TI - Survey of the opinions of general practitioners about health services in a rural setting. AB - OBJECTIVES: Using a tested survey protocol, to obtain under comparable circumstances the opinions and subjective assessments of general practitioners regarding health care services in a contrasting rural health district, to obtain indications of those services which, by reason of the opinions of general practitioners in relation to their quantity and quality, might benefit from further enquiry or even detailed assessment and, as in the previous survey, to facilitate the close working with general practitioners without which population based needs assessment and further enquiry and research into the development of healthcare services will be handicapped. DESIGN: A postal questionnaire survey of all general practitioners in the health district. SETTING: North Lincolnshire health district. SUBJECTS: One hundred and forty eight general practitioners, of whom 104 responded, two by letter only. MAIN OUTCOME MEASURES: Scores of quantity and of quality for 24 hospital services and 32 community services. The frequency with which services were identified as a priority for improvement, and written comments about the services surveyed. RESULTS: Most services were thought by general practitioners to be adequate or better in both quantity and quality, involving a surprising degree of agreement. In only six of the 56 services were these considered by more than 50% of the doctors responding to be inadequate or grossly inadequate in quantity, and in only eight services were these found by more than 15% of doctors to be poor or very poor in quality. Complaints about quantity of service were more frequent than complaints about quality of service, and community services received more complaints from general practitioners about both quality and quantity than the hospital services. The services most general practitioners wanted improved were orthopaedics, psychiatry, physiotherapy and chiropody. CONCLUSIONS: This survey confirmed the suitability of the postal questionnaire for assessing the impressions of general practitioners about both the quantity and quality of services available in their support. Consistent agreement between general practitioners about the services surveyed parallel a comparable survey undertaken in a largely urban area, showing close similarities with the results of this survey with only relatively minor local variations. The results provide pointers for health needs assessment of key services. PMID- 8475245 TI - Assessment of the effectiveness of primary health care interventions in the control of three intestinal nematode infections in rural communities. AB - In a 30 months' longitudinal study, primary health care intervention was effective in reducing the prevalence of three common intestinal nematode infections (Ascaris lumbricoides, Trichuris trichiura and Necator americanus) in three communities. This was achieved by training school leavers and auxiliary aides as microscopists, health inspectors and field assistants and deploying them to provide screening, surveillance, environmental sanitation, and mass-expulsion chemotherapy (MEC). Post-control surveillance confirmed that the prevalence of these infections had been greatly reduced. The prevalence of Ascaris lumbricoides had declined from 49.3% (pre-intervention) to 10.5% (post-intervention). Hookworm had fallen from 31.4% (pre-intervention) to 4.1% (post-intervention) and whipworm from 40.7% (pre-intervention) to 6.5% (post-intervention). Overall percentage decreases of 78.7%, 86.9% and 84.0% were recorded for Ascaris lumbricoides, Necator americanus and Trichuris trichiura respectively. The initial decline in prevalence was due to the MEC campaign, but the improved sanitation and health education presumably reduced the reinfection rate. If the entire population participated, periodic repetition of the mass expulsion therapy campaign at appropriate intervals combined with continued attention to environmental hygiene and prolonged health education could bring these infections under control within a few years. PMID- 8475246 TI - A case-control study of congenital hip dislocation. AB - In this study we have investigated various epidemiological factors which may be related to congenital dislocation of the hip (CDH). Eighty-one cases born during the period 1st January 1988 to 31st August 1990, with four matched controls per case, were identified from consultants' records held at the Queen's Medical Centre and City Hospital, Nottingham. One hundred and twenty-four subjects who were referred to a new Hip Instability Clinic with suspected CDH, but not diagnosed or treated for CDH, were also included as a third group. Information about the mother's pregnancy, previous medical history and family history was collected from obstetric records kept at the two hospitals. Multigravidae and similarly multiparous women had a statistically significantly reduced risk of having a baby with CDH. The relative risks were 0.55 (95% confidence interval 0.33, 0.93) and 0.53 (95% confidence interval 0.31, 0.91) respectively. The method of delivery was also of importance. Babies born by Caesarean section or in breech position had an increased risk of CDH which was statistically significant. Using addition clinical information obtained from subjects attending the Hip Instability Clinic we also found that cases were more likely to have a family history of CDH than subjects who were screened for CDH but found to be normal. PMID- 8475247 TI - A mathematical formalism describing the yield of radiation-induced single- and double-strand DNA breaks, and its dependence on radiation quality. AB - The purpose of this paper is to describe mathematically the observed dependence of the number of DNA single-strand breaks (SSBs) per unit dose on radiation quality (e.g., LET) by invoking the concept of matrix saturation (i.e., the fact that a nucleotide can be the site of one SSB only and therefore further local energy deposition is wasted), and to show that, based on this, one obtains a characteristic variation of the yield of DNA double-strand breaks with variation of LET, in qualitative agreement with certain experimental determinations. The formalism developed here makes use of methodology from the field of integral geometry, introduced by Kellerer [Radiat. Prot. Dosim. 31, 9-16, 1990] in microdosimetry. PMID- 8475248 TI - Evidence for induction of DNA double-strand breaks at paired radical sites. AB - Isolated plasmid pBR322 DNA was irradiated in the gas explosion apparatus in the presence of 10 mmol dm-3 GSH. By varying the time of the oxygen shot relative to the 5-ns pulse of electrons, the chemical repair kinetics of the oxygen-dependent free-radical precursors of DNA single- and double-strand breaks (SSBs and DSBs) can be determined. The first-order repair rate of the SSB precursors was 1370 s-1 in comparison to 2900 s-1 for DSB precursors. Under these conditions the oxygen enhancement ratio for SSBs was 3.0 in comparison to 7.5 for DSBs. This twofold difference in chemical repair rate may be interpreted on the basis of the free radical precursor of a DSB consisting of two radicals, one on either strand of the DNA. With the chemical repair of one or other of these radicals by hydrogen atom donation from GSH, a DSB is not produced. This process will occur at twice the rate of the chemical repair of an SSB precursor consisting of a single radical. These data are consistent with the concept that DSBs are formed at the sites of clustered energy depositions with the production of a paired radical. PMID- 8475249 TI - Comments on the distribution of clonogens in irradiated tumors. PMID- 8475250 TI - On the radiation-acoustic effect in radiobiology. PMID- 8475251 TI - Potentiation of photodynamic therapy by mitomycin C in cultured human colon adenocarcinoma cells. AB - The effects of photodynamic therapy (PDT) alone and in combination with Mitomycin C (MMC) on WiDr cells, a human colon adenocarcinoma cell line, were investigated. The addition of MMC increased the cytotoxicity of PDT. The presence of MMC resulted in a reduction or a removal of the shoulder of the PDT survival curves as well as an increase in their slopes. Increasing with the concentrations of MMC from 0.01 to 0.025 micrograms/ml, the cytotoxic effects of the two treatments changed from additivity to supra-additivity as judged by comparing dose-response curves for each treatment alone with survival curves after combination therapy and by isobologram analysis. The cytotoxicity of MMC could also be enhanced by a practically nontoxic treatment of PDT (8% cell inactivation). The cytotoxicities of MMC and PDT in combination were found to be dependent on the sequence of the two treatments. When MMC (> or = 0.02 micrograms/ml) and Photofrin II were given simultaneously for 16 h and then followed by irradiation, the combination was found to be more effective than when MMC was given to the cells immediately after PDT and kept in the medium for 16 h. Possible mechanisms of the combination effects of PDT and MMC are discussed briefly. PMID- 8475252 TI - Sequential analysis of the pathogenesis of plutonium-induced pulmonary neoplasms in the rat: morphology, morphometry, and cytokinetics. AB - Light microscopy, morphometry, and cytokinetic techniques were used to examine the dynamics of plutonium-induced pulmonary proliferative lesions and neoplasms in rats at several intervals to 450 days after inhalation exposure to aerosols of 239PuO2. Maximal increases in alveolar and bronchiolar epithelial cell labeling were seen at 30 days; decreasing subsequently, the levels remained elevated above control indices. Focal proliferative epithelial lesions developed in the lung by 180 days and before the onset of pulmonary neoplasms. Pulmonary neoplasms, predominantly adenocarcinomas and squamous cell carcinomas, were initially observed at 308 days. The proliferative lesions progressed through a succession of morphological changes leading to the development of neoplasms. The volume density (fraction) and epithelial surface area of foci of alveolar epithelial hyperplasia increased progressively between 180 and 450 days after exposure, in contrast to the other proliferative lesions. We conclude that plutonium-induced pulmonary neoplasms develop through a succession of focal proliferative lesions that represent developmental preneoplastic lesions. Progressive increases in volume and epithelial surface area of the alveolar epithelial hyperplasias suggest that they may be more at risk for neoplastic transformation than the other histological types of proliferative foci. PMID- 8475253 TI - A study of radiation necrosis and edema in the canine brain using positron emission tomography and magnetic resonance imaging. AB - Radiation injury, a major hazard of central nervous system (CNS) radiotherapy, was investigated using sequential studies with positron emission tomography (PET) and magnetic resonance imaging (MRI) in beagle dogs with both helium and neon-ion hemibrain irradiation. All dogs receiving 7.5-11 Gy of neon showed no signs of radiation injury to 3 years after irradiation. Dogs receiving > or = 13 Gy neon or helium succumbed to radiation necrosis and died 21-32 weeks after irradiation. The findings of imaging studies for all dogs who succumbed to radiation necrosis were normal until 3-6 weeks before death. Sequential studies were performed using 0.5 T MRI spin-echo and inversion recovery imaging sequences, and high-resolution (2-3 mm) PET with 18F deoxyglucose and 82Rb. The same axial slices (within 1-2 mm) were imaged repeatedly (weekly) after irradiation until death. The earliest CNS changes were seen as decreased metabolic activity in the cortex of the irradiated hemisphere with PET or an increase in signal intensity in the periventricular white matter on T2-weighted spin-echo imaging on MRI. From the time this increase in signal intensity was first observed, T1 and T2 values increased steadily in both the gray and white matter until death. The changes in white matter were consistently greater than those in gray matter. The results of PET, MRI, and histopathological examinations support the theory that both cellular and vascular mechanisms are involved in radiation necrosis. PMID- 8475254 TI - Differential response of the permeability of the rat liver canalicular membrane to sucrose and mannitol following in vivo acute single and multiple exposures to microwave radiation (2.45 GHz) and radiant-energy thermal stress. AB - Both acute and chronic exposures to microwave radiation altered the function of the rat canalicular membrane. A single acute exposure to microwave radiation [80 mW/cm2, 2.45 GHz, continuous wave, 30 min exposure (SAR approximately equal to 72 W/kg)] or a matched radiant-energy thermal load, both designed to raise core body temperature approximately 3 degrees C, decreased the permeability of the canalicular membrane of male Sprague-Dawley rats to sucrose. The change in canalicular membrane permeability was demonstrated by a significant increase in the percentage of [3H]sucrose recovered in bile following its administration by a segmented retrograde intrabiliary injection. Similar acute exposures to microwave and radiant-energy thermal sources produced no significant alterations in canalicular membrane permeability to [14C]mannitol. In both acute exposure protocols, a rapidly reversible increase in bile flow rate was observed. Four exposures (30 min/day x 4 days) to either microwave radiation (80 mW/cm2) or a matched radiant-energy thermal load resulted in a significant depression in bile flow rate at normothermic temperatures. Animals receiving multiple exposures to microwave radiation had significant decreases in canalicular membrane permeability to both [3H]sucrose and [14C]mannitol, while similar exposure to radiant-energy thermal load alone altered canalicular membrane permeability to [3H]sucrose. An examination of the hepatic clearance of sucrose and mannitol following acute microwave exposure demonstrated no significant differences. Thus acute single exposure to microwave and radiant-energy thermal loads produced similar alterations in canalicular membrane permeability. Conversely, multiple exposures produced nonreversible changes in bile flow rate and canalicular membrane permeability, with microwave exposure producing greater alterations in the function of the canalicular membrane than an equivalent radiant-energy thermal load. PMID- 8475255 TI - Temporal modulation of TGF-beta 1 and beta-actin gene expression in pig skin and muscular fibrosis after ionizing radiation. AB - Although radiation-induced fibrosis has long been characterized by excess fibroblast proliferation and extracellular matrix deposition, the origin of cell activation in these complications of radiotherapy or radiation accidents is still controversial. The present work was designed to test the hypothesis that the abnormal production of TGF-beta 1 in irradiated tissues results in continuous signals for tissue repair and long-term cell activation. We examined gene expression of this growth factor in a well-characterized pig model of radiation induced fibrosis, using Northern-blot and slot-blot hybridizations and indirect immunofluorescence. We found that the TGF-beta 1 mRNA level was increased 19-fold in the irradiated skin during the early erythematous phase, which started 3 weeks after irradiation. During the later phases of fibrosis, from 6 to 12 months after irradiation, the TGF-beta 1 gene was highly expressed in the repaired skin and the underlying muscular fibrotic tissue, with 10- and 8-fold maximal increases, respectively. In addition, we found that the beta-actin mRNA level was increased in the fibrotic tissue. Immunostaining for TGF-beta 1 revealed the presence of the protein in endothelial cells of capillaries, in myofibroblasts, and in the collagenous matrix of the fibrotic tissue. These results suggest that TGF-beta 1 may be one of the key cytokines involved in the cascade of events that leads to radiation-induced fibrosis, at both early and late stages. PMID- 8475256 TI - On the equivalent dose for Auger electron emitters. AB - Radionuclides that emit Auger electrons are widely used in nuclear medicine (e.g., 99mTc, 123I, 201Tl) and biomedical research (e.g., 51Cr, 125I), and they are present in the environment (e.g., 40K, 55Fe). Depending on the subcellular distribution of the radionuclide, the biological effects caused by tissue incorporated Auger emitters can be as severe as those from high-LET alpha particles. However, the recently adopted recommendations of the International Commission on Radiological Protection (ICRP) provide no guidance with regard to calculating the equivalent dose for these radionuclides. The present work, using spermatogenesis in mouse testis as the experimental model, shows that the lethality of the prolific Auger emitter 125I is linearly dependent on the fraction of the radioactivity in the organ that is bound to DNA. This suggests that the equivalent dose for Auger emitters may have a similar linear dependence. Accordingly, a formalism for calculating the equivalent dose for Auger emitters is advanced within the ICRP framework. PMID- 8475257 TI - Effects of in vivo heart irradiation on myocardial energy metabolism in rats. AB - To investigate the effect of in vivo heart irradiation on myocardial energy metabolism, we measured myocardial adenosine nucleotide concentrations and mitochondrial oxygen consumption in left ventricular tissue of rats 0-16 months after local heart irradiation (20 Gy). At 24 h and 2 months no difference in myocardial adenosine nucleotide concentration was apparent between irradiated and control hearts. The total myocardial adenosine nucleotide concentrations in irradiated hearts compared to those of nonirradiated controls tended to be lower from 4 months onward. The rate of oxidative energy production (state 3 respiration) in irradiated hearts was significantly reduced compared with that of age-matched controls from 2 months onward. Moreover, as a result of aging, a time dependent decrease in the rate of oxidative energy production was observed in both irradiated and control hearts (P < 0.001). The respiratory control index (RCI = oxygen consumption in state 3/oxygen consumption in state 4) in irradiated hearts was not different from the RCI measured in age-matched control animals. During the period of study the RCI diminished significantly with age in both groups (P < 0.005). The number of oxygen atoms used per molecule of ADP phosphorylated (P/O ratio) was not influenced by the irradiation. The P/O ratio for the NAD(+)-linked substrates remained unchanged at a value of about 3 during the period studied. At 6 months after irradiation activities of myocardial enzymes such as lactate dehydrogenase, creatine kinase, citrate synthase, and cytochrome c oxidase were reduced. The reduction in myocardial energy production and the changes in energy supplies provide a mechanism to explain impaired contractility after local heart irradiation. PMID- 8475258 TI - Amelioration of radiation nephropathy in rats by dexamethasone treatment after irradiation. AB - The effect of 20 Gy intraoperative bilateral local kidney irradiation was compared in rats treated after irradiation with dexamethasone and untreated rats. Ninety days after irradiation, body weights, WBC, RBC, hematocrit, and renal function (plasma urea nitrogen concentration and retention of ethylenediaminetetraacetic acid) were measured. The animals were then sacrificed and the kidneys were analyzed for water and hydroxyproline content and examined histologically. Local kidney irradiation reduced animal growth, prevented renal growth, decreased renal mass and renal function, and increased the water and hydroxyproline content of the kidneys. Histopathological examination revealed glomerular damage (atrophy, decreased RBC and endothelial cells, increased mesangial matrix), tubular damage (epithelial denudation, congestion with hyalin casts), and increased concentration of interstitial cells. Dexamethasone treatment significantly ameliorated the effects of kidney irradiation on body weights, renal mass, renal function, and the development of anemia. Dexamethasone had no effect on radiation-induced edema or fibrosis as measured by the water and hydroxyproline content of the kidneys. Dexamethasone-treated irradiated kidneys had significantly less damage to the glomeruli and tubules. The results suggest that dexamethasone is cytoprotective and prevents the destruction of the nephron. PMID- 8475259 TI - Depth-dose equivalent relationship for cosmic rays at various solar minima. AB - Galactic cosmic rays (GCR) pose a serious radiation hazard for long-duration missions. In designing a lunar habitat or a Mars transfer vehicle, the radiation exposure determines the shielding thickness, and hence the weight of spacecraft. In designing a habitat one has to focus on the worst-case radiation flux and its uncertainties. Using the spherically symmetric diffusion theory of the solar modulation of GCR, and data on the differential energy spectra of hydrogen, helium, oxygen, and iron from 1965 to 1989, it has been shown that the flux is determined by the diffusion parameter which is a function of the time in the solar cycle. This analysis also showed that the fluxes in the 1954 and 1976-1977 solar minima were similar and higher than those in 1965. In this paper, we have extended the spherical solar modulation theory back to 1954. These results show that the 1954-1955 GCR flux was nearly the same as that from 1976 to 1977 and that the 1965 flux values were nearly the same as those in 1986. Using this theory we have obtained the GCR spectra for all the nuclei and calculated the depth dose as a function of aluminum thickness. Using the ICRP 26 value for the quality factor, and the 1976-1977 spectra, it is shown that the shielding required to stay below 0.5 Sv is 17.5(-3)+8 g cm-2 of aluminum, and 9(-1.5)+5 g cm-2 to stay below 0.6 Sv. The calculated dose equivalent using the ICRP 60 values for quality factors is about 15% higher than that calculated using the ICRP 26 value. However, the errors on the quality factor itself may be substantial and are not taken into account. PMID- 8475260 TI - A longitudinal study of growth and development of stature among prenatally exposed atomic bomb survivors. AB - Growth retardation due to exposure to the atomic bomb has been evaluated using repeated measurements of stature from 10 to 18 years of age. A highly significant growth retardation due to the DS86 uterine dose was observed in all trimesters combined and in the first and second trimesters of pregnancy. In the first trimester, all parameter estimates based on a linear (L) or linear-quadratic (L Q) dose-response relationship were negative in relation to the DS86 uterine dose. The positive dose estimate in the second trimester is small and close to the control level. Statistically significant difference was determined by a multivariate test statistic examining whether or not a set of two- or three parameter estimates including a constant term related to an L or L-Q dose response relationship was different from zero. A radiation-related growth retardation was demonstrable as a longitudinal result of the repeated measurements of stature. The dose effect in the third trimester was not significant under either the L or the L-Q model. The relationship between birth weights and repeated measurements of stature in adolescence is discussed based on the results obtained by a growth curve analysis. PMID- 8475261 TI - Radiology and the law, with an emphasis on interventional radiology. PMID- 8475262 TI - Another look at the radiology relative value scale. PMID- 8475263 TI - Radiology relative value scale, physician payment reform, and the U.S. health care policy agenda. PMID- 8475264 TI - Flat adenomas: what you can't see can hurt you. PMID- 8475265 TI - Pediatric radiology: flexibility, viability, credibility, and opportunity. PMID- 8475266 TI - Patient-focused care: radiology department beware. PMID- 8475267 TI - The radiology relative value scale: its development and implications. AB - In a proactive response to federal government cost-containment pressures, the radiology profession, under the leadership of the American College of Radiology (ACR), in 1988 developed a relative value scale (RVS) for radiologic procedures. Like earlier radiology RVSs, its relative values reflected the physician work and practice costs involved in each procedure. The RVS was constructed by using (a) three types of data (magnitude estimation, charges, and practice costs) obtained by means of surveys and (b) expert consensus panels involving participants from all fields and many organizations in radiology. The RVS was accepted, essentially in toto, by Medicare. Subsequently, the RVS has required much work to correct errors by Medicare and the insurers that administer it, to improve procedure codes, and to develop codes and relative values for new procedures. By moving proactively, radiology preserved fee-for-service against a major threat, reduced payment cuts from those that seemed to be impending, and gained a unique degree of control over its payments. However, the new payment system is complex and does not reward efficacy, cost-effectiveness, or quality. PMID- 8475268 TI - Dynamic contrast-enhanced CT of the liver: comparison of contrast medium injection rates and uniphasic and biphasic injection protocols. AB - To determine the effect of contrast medium injection rate and biphasic versus uniphasic bolus on hepatic parenchymal enhancement at computed tomography (CT), 105 patients were randomized into four protocols. Hepatic and aortic enhancement curves were measured for each protocol. The optimal scanning interval (the duration between onset of a desired hepatic enhancement threshold and decline of enhancement below the threshold or onset of the equilibrium phase) and contrast enhancement index (CEI) (area under the hepatic enhancement curve above a desired threshold during the nonequilibrium phase) were the primary determinants of merit. Measurements were performed at hepatic enhancement thresholds between 10 and 60 HU. At most thresholds of hepatic enhancement, optimal scanning intervals were significantly longer and CEIs were significantly higher for the biphasic protocols than for the uniphasic protocols (P < .03). A biphasic injection with a high initial flow rate produces high peak contrast enhancement but delayed onset of equilibrium and thus provides a longer optimal scanning interval. PMID- 8475269 TI - Interstitial hyperthermia of colorectal liver metastases with a US-guided Nd-YAG laser with a diffuser tip: a pilot clinical study. AB - Ultrasound (US)-guided interstitial hyperthermia performed with the neodymium yttrium aluminum garnet laser with a diffuser tip involves placement of a laser fiber in solid tissue followed by irradiation from within the center of the tumor to be treated. The authors previously described the development of a US-guided technique that permits simultaneous interstitial laser irradiation and temperature measurements, with real-time US monitoring. With the use of a dedicated diffuser tip modification of the bare laser fiber, it has proved possible to produce spherical coagulations with a diameter comparable to that of liver metastases of clinical relevance. This technique was used in 11 patients with 16 colorectal liver metastases, 12 of which were radically ablated. Real time US and interstitial temperature monitoring during treatment had a positive predictive value of 86% and negative predictive value of 100% in judging the final result. The technique is feasible, effective, and safe, but the effect on patient survival must be tested in future randomized clinical studies. PMID- 8475270 TI - Hepatic metastases: interstitial laser photocoagulation with real-time US monitoring and dynamic CT evaluation of treatment. AB - Fifty-five liver metastases in 21 patients were treated with interstitial laser photocoagulation (ILP). Tumors were irradiated with a neodymium yttrium aluminum garnet laser via optical fibers passed through 19-gauge needles inserted under ultrasound (US) guidance. Heating of the tumor was evident at real-time US as an expanding and coalescing echogenic zone around the needle tips. After ILP, dynamic computed tomography (CT) showed laser-induced necrosis as a new area of nonenhancement. Necrosis of tumor volume was more than 50% in 82% (45 of 55) of the tumors, and 100% necrosis was achieved in 38% (21 of 55). Metastases smaller than 4 cm in diameter were treated more effectively and required fewer treatment sessions than did those larger than 4 cm. Complications were minor and included severe pain in four cases, persistent pain for up to 10 days in 11 cases, and asymptomatic subcapsular hematoma (four cases) and pleural effusion (six cases) seen with CT. ILP is safe and effective for liver tumor destruction, and US and CT are useful in different aspects of treatment monitoring. PMID- 8475271 TI - Self-localization in US of appendicitis: an addition to graded compression. AB - Graded-compression ultrasound (US) of the right lower quadrant (RLQ) has been a valuable addition to the diagnostic evaluation of acute appendicitis. In an effort to expedite the sonographic evaluation and improve diagnostic accuracy, a method of self-localization was added to the standard graded-compression examination. A total of 236 patients with signs of appendicitis were studied. Eighty-five percent (121 of 142) of the patients with proved appendicitis were able to decisively self-localize their pain. Of the patients without appendicitis who still had significant disease in the RLQ, 88% (29 of 33) were able to self localize their pain, with an accuracy rate of 86% for significant disease. Among patients without significant disease, only 15% (nine of 61) self-localized their pain. This "sonographic self-localization sign" reduced the time of the examination and was a valuable addition to standard graded-compression US of the appendix. PMID- 8475272 TI - Gastrocolic fistulas: the increasing role of aspirin. AB - Eight patients had gastrocolic fistulas depicted on barium studies at the authors' hospital during a 10-year period between 1982 and 1992. Seven of those patients (88%) had benign disease, including aspirin-induced gastric ulcers of the greater curvature (n = 4), granulomatous colitis (n = 1), tuberculosis (n = 1), and a penetrating anastomotic ulcer after partial gastrectomy (n = 1). The remaining patient had a malignant gastrocolic fistula caused by carcinoma of the transverse colon. Two patients (25%) experienced classic symptoms of gastrocolic fistulas (ie, feculent vomiting or foul-smelling eructations), but the other six (75%) experienced abdominal pain or other nonspecific clinical findings. In the four patients who were taking aspirin, upper gastrointestinal examinations revealed giant penetrating ulcers of the greater curvature that communicated with the superior border of the transverse colon via a fistula. Three of these patients exhibited marked clinical improvement after conservative medical treatment and did not need surgery. This experience suggests that aspirin-induced gastric ulcers of the greater curvature have become a more common cause of gastrocolic fistulas than is carcinoma of the stomach or transverse colon. PMID- 8475273 TI - Gastric and esophageal varices: 20-MHz transnasal endoluminal US. AB - To image esophageal and gastric varices qualitatively and to measure esophageal varices quantitatively, 29 patients with portal hypertension underwent transnasal esophageal and gastric ultrasonography (US). Twenty-three patients underwent standard endoscopy. Endoluminal US demonstrated the varices as anechoic areas with communications in the submucosal, periesophageal, and perigastric regions, as well as ascites visualized through the gastric wall. Interobserver variation between two investigators for measurements of the largest esophageal varix in each patient was r value of .99 for diameter, r value of .99 for cross-sectional surface area, and r value of .98 for circumference. Endoscopy for evaluation of gastric varices had a sensitivity of 48% and a specificity of 50% and for evaluation of esophageal varices had a sensitivity of 94% and a specificity of 17%. Periesophageal and perigastric varices could not be visualized at endoscopy. Transnasal esophageal US, a new imaging technique with which to detect and measure esophageal varices, is a more sensitive modality than endoscopy for the detection of gastric varices. PMID- 8475274 TI - Colorectal adenomas: inflammatory changes that simulate malignancy after laser coagulation--evaluation with transrectal US. AB - To evaluate the assumption that inflammatory changes in the rectal wall after treatment of colorectal adenoma with photocoagulation may simulate malignant infiltration, the findings were reviewed in 23 follow-up examinations performed with transrectal ultrasound (TRUS) in 17 patients with benign adenoma. Special attention was given to the appearance of the wall layers underneath the adenoma. After partial coagulation, changes in the colorectal wall were usually seen on TRUS scans obtained early in follow-up; sometimes the thickened muscle layer had an irregular outer margin. In three of the 13 early examinations, lesions mimicked malignancy. To correlate these findings with histologic proof, an experimental study was performed: Colorectal specimens from pigs were examined with ultrasound (US) and microscopy. The abnormal sonographic appearance of specimens on US scans was caused by an inflammatory reaction in the deep wall layers; concomitant serositis appeared to be responsible for the malignancy mimicking irregular outer margin. In screening for malignancy in colorectal adenoma, TRUS may cause overstaging during the first 6 weeks after polypectomy or after a session of laser treatment and should be avoided. PMID- 8475275 TI - CT findings after percutaneous biliary procedures. AB - A prospective study was performed to determine the frequency, type, and extent of abnormalities depicted with computed tomography (CT) after percutaneous biliary procedures (PBPs). Abdominal CT scans were obtained 24-72 hours after the PBP in 31 consecutive cases in 29 patients. Fifteen abnormalities were proved with CT in 14 patients (45%), as follows: subcapsular hematoma (two patients), subcapsular or perihepatic fluid collection (three patients), intrahepatic hematoma (three patients), nonspecific intrahepatic fluid collection (three patients), subcutaneous hematoma at the puncture site (one patient), free intraperitoneal air (one patient), intraperitoneal collection of contrast material (one patient), and inadvertent transxiphoid catheter tract (one patient). Only five of these patients had clinically apparent post-PBP complications that could be explained with CT findings. The 14 patients with positive CT findings required more needle passes (mean, 8.3 vs 4.6) during the PBP, had a difficult PBP more often (five patients [36%] vs four patients [27%]), and had more frequent placement of an internal-external drain (nine patients [64%]) than those with negative findings (eight patients [53%]). Positive findings on CT scans are common after a PBP and often are not associated with clinical symptoms. PMID- 8475276 TI - Minute nonpolypoid adenomas of the colon depicted with barium enema examination. AB - To evaluate the usefulness of barium enema examination for detection of small nonpolypoid adenomas, the barium enema study findings were reviewed in patients with flat or depressed adenomas of the colon 3-5 mm in diameter that had been initially found during colonoscopy and that had been diagnosed as adenomas at histologic analysis. Eleven of the 21 nonpolypoid adenomas were depicted on radiographs; they tended to be located on the left side of the colon. The 10 other lesions were not detected retrospectively on barium enema radiographs. The radiographic findings in the depicted lesions included smooth, round, radiolucent areas; in seven of these lesions, round or irregular barium flecks were also seen. The radiolucent areas were attributed either to slightly elevated growth of adenomas or to surrounding hyperplasia of nonneoplastic glands; the central barium fleck seemed to conform to depressed areas within adenomas. Barium enema examination can demonstrate nonpolypoid adenomas of the colon, even though colonoscopy seems superior to barium enema examination for detection of these lesions. PMID- 8475277 TI - Abdominal staging of thoracic Hodgkin disease: CT-lymphangiography-Ga-67 scanning correlation. AB - A retrospective study was performed to assess whether lymphangiography and gallium-67 scanning were complementary to computed tomography (CT) in abdominal staging of disease in 94 patients with early-stage thoracic Hodgkin disease. In 51 patients with surgical or follow-up correlation, the spleen was involved in 16% (n = 8), the spleen and lymph nodes in 22% (n = 11), and only lymph nodes in 2% (n = 1). In these 51 patients, none of the imaging modalities had greater than 50% sensitivity for the detection of nodal involvement. The overall accuracy was similar (71%-82%) for each modality. Analysis of subgroups of patients with lymph nodes measuring less than 10 mm, 10-19 mm, or 20 mm or greater at CT revealed that lymphangiography and gallium scanning added little to the positive or negative predictive values of CT. The sensitivity of CT for detection of splenic disease was 11% (two of 19). On the basis of surgical or follow-up correlation in 51 patients, the authors conclude that lymphangiography and gallium scanning offer minimal or no complementary benefit. PMID- 8475278 TI - Upper inferior vena caval anastomotic stenosis in liver transplant recipients: Doppler US diagnosis. AB - Ultrasound (US) is routinely used as a screening tool for liver transplant dysfunction. Its use in the detection of significant vascular complications of liver transplantation such as thrombosis or stenosis of the hepatic artery and portal vein is well recognized. Its role in the detection of anastomotic stenosis of the inferior vena cava (IVC) has not been defined. The authors present US findings in five patients with such stenosis. The gray-scale and Doppler findings in all cases consisted of loss of normal hepatic vein and IVC periodicity. Some studies also showed distention of the hepatic veins and IVC and a high-velocity jet at the anastomosis, and in one case the stenosis was visualized with color Doppler US. While there are other causes of absent periodicity in the hepatic veins, this finding in the appropriate clinical setting may be a sensitive indicator of upper IVC anastomotic stenosis. PMID- 8475279 TI - Hepatic artery: effect of a meal in healthy persons and transplant recipients. AB - Thirty healthy volunteers and 12 liver allograft recipients (two with cirrhotic changes seen at microscopy) were given a standard meal. Doppler sonography of the right and left hepatic arteries, the superior mesenteric artery, and the portal vein was performed. The change in hepatic arterial resistance was evaluated with the resistive index (RI). After the standard meal, portal venous flow increased in both the healthy volunteers and allograft recipients (more so in the latter group). Superior mesenteric arterial RI decreased in all subjects. A postprandial increase in hepatic arterial RI, likely reflecting constriction of the hepatic artery, was seen in both groups. It was absent in the two patients with recurrent transplant cirrhosis. These results show the importance of examining hepatic arterial flow in the fasting subject, since high resistance after a meal may be falsely interpreted as a sign of disease. Absence of a postprandial change in resistance of the hepatic artery could signal abnormal liver function. PMID- 8475280 TI - Survey of reproductive health among female MR workers. AB - Epidemiologic data were obtained to evaluate potential risks from exposure to the static and time-varying magnetic fields used in magnetic resonance (MR) imaging. A questionnaire sent to women workers in more than 90% of clinical MR facilities in the United States addressed menstrual-reproductive experiences, work activities, and potential confounders (eg, age, smoking, alcohol use). In 1,915 completed questionnaires, 1,421 pregnancies were reported: 280 occurred in an MR worker (technologist or nurse), 894 in an employee in another job, 54 in a student, and 193 in homemakers. Comparing MR-worker pregnancies with those occurring in employees at other jobs, a relative risk ratio of 1.27 (95% confidence interval [CI], 0.92-1.77) was found for spontaneous abortions; for conception taking more than 12 months, 0.90 (CI, 0.54-1.51); for delivery before 39 weeks, 1.19 (CI, 0.76-1.88); for birth weight below 5.5 lb (2.5 kg), 1.01 (CI, 0.50-2.04); and for male gender of the offspring, 0.99 (CI, 0.80-1.22). Adjustment for maternal age, smoking, and alcohol use also failed to markedly change any of the associations. These results suggest that there is not a substantial increase in these common adverse reproductive outcomes. PMID- 8475281 TI - Coronary arteries: three-dimensional MR imaging with fat saturation and magnetization transfer contrast. AB - Magnetic resonance imaging of the coronary arteries is a particularly difficult task because of the small size of the vessels and the motion of the heart during the cardiac and respiratory cycles. The authors developed a non-breath-hold three dimensional (3D) technique to accomplish this goal. Imaging was performed with voxel sizes of 1.50-4.50 mm3. This allows for excellent multiplanar reconstruction to view the coronary arteries from any angle. The short echo time usually makes blood isointense with surrounding tissue since inflow enhancement is weak with a thick-slab 3D method. This problem is overcome by applying fat saturation and magnetization transfer contrast techniques to suppress the signals of fat and myocardium surrounding the coronary arteries. Respiratory motion artifacts are reduced by taking four acquisitions and averaging the data. The authors acquired the first 3-10 cm of both the left and right coronary arteries in most cases in 7-10 minutes with single slab coverage. Acquisition of multiple slabs should further increase the length of coverage of the coronary arteries. Further improvements will occur when respiratory gating is used. PMID- 8475282 TI - Phase-contrast cine MR angiography in chronic liver disease. AB - Thirty-one patients with portal venous hypertension underwent phase-contrast cine magnetic resonance (MR) angiography to validate the technique for assessment of main portal vein patency and blood flow direction. Correlative findings from Doppler ultrasonography, conventional angiography, and surgery were acquired in 30, 17, and 16 patients, respectively. Findings from MR angiography correlated well with those of the other methods for determining portal vein patency and flow direction. The main portal vein was patent in 29 patients and was thrombosed in two patients at MR angiography. With the use of a 40-mm slab projection acquisition that required 5 minutes, the splenic and superior mesenteric veins, as well as extensive varices (when present), were seen in the majority of cases. Phase-contrast cine MR angiography is an accurate method of rapidly assessing morphologic characteristics, patency, and flow direction of the portal venous system and thus is a useful method for evaluating the condition of patients with chronic liver disease. PMID- 8475283 TI - Creation of transjugular intrahepatic portosystemic shunts with the wallstent endoprosthesis: results in 100 patients. AB - One hundred patients underwent transjugular intrahepatic portosystemic shunt (TIPS) creation for variceal bleeding (n = 94), intractable ascites (n = 3), hepatorenal syndrome (n = 2), and preoperative portal decompression (n = 1). Shunts were completed in 96 patients. Portal vein pressure was reduced from 34.5 mm Hg +/- 7.6 (standard deviation) to 24.5 mm Hg +/- 6.2; the residual portal vein-hepatic vein gradient was 10.4 mm Hg +/- 0.9. Acute variceal bleeding was controlled in 29 of 30 patients. Of the 96 patients who underwent successful TIPS creation, 26 have died and 22 have undergone liver transplantation; the remaining 48 patients have survived an average of 7.6 months. Variceal bleeding recurred in 10 patients. Fifteen patients developed shunt stenosis (n = 6) or occlusion (n = 9). Patency was reestablished in eight of the nine occluded shunts. Seventeen patients developed new or worsened encephalopathy. The authors conclude that TIPS creation is an effective and reliable means of lowering portal pressure and controlling variceal bleeding, particularly in patients with acute variceal bleeding unresponsive to sclerotherapy and patients with chronic variceal bleeding before liver transplantation. PMID- 8475284 TI - Inversion-recovery fast spin-echo MR imaging: efficacy in the evaluation of head and neck lesions. AB - To compare the efficacies of fast spin-echo (FSE) and inversion-recovery FSE (IRFSE) magnetic resonance (MR) imaging in evaluating head and neck disorders, the authors evaluated 46 lesions in 23 consecutive patients. Twenty-seven lesions were related to neoplasms; 19 lesions resulted from infectious, allergic, or radiation-induced inflammation. Conventional T1-weighted, FSE, and IRFSE images were obtained in all patients. The FSE and IRFSE images were qualitatively compared in an unblinded manner for conspicuity of lesion margins and extent. IRFSE imaging improved conspicuity of 22 lesions (48%) and showed equal conspicuity of 18 (39%). IRFSE imaging proved most useful for small lesions with long T2 relaxation times that were surrounded by fat. IRFSE imaging improved visibility of small optic nerve gliomas, salivary gland inflammation, peripheral nerve tumors, and small lymph nodes. Early changes secondary to spread of tumor across fascial planes were also well visualized with IRFSE sequences. In six lesions (13%) that did not have long T2 relaxation times, the FSE images provided better conspicuity. The authors conclude that by improving conspicuity of small lesions adjacent to or surrounded by fat, IRFSE sequences can supplement FSE sequences in imaging the head and neck. PMID- 8475285 TI - Epidural hematoma of the lumbar spine: 18 surgically confirmed cases. AB - The authors report 18 cases of surgically proved spontaneous epidural hematoma of the lumbar spine. The clinical findings in spontaneous epidural hematoma were identical to those in acute disk herniation. Underlying disk abnormalities were common; the majority of hematomas (14 of 18, 78%) were associated with small concomitant disk herniations or underlying annular tears. The magnetic resonance imaging and computed tomographic findings were similar to those in extruded/free fragment disk herniation. The strong coincidence between epidural hematoma and underlying disk disruption (annular tear or herniation) leads the authors to postulate that spontaneous epidural hematoma results from tearing of fragile epidural veins lying adjacent to the displaced anulus or nucleus. PMID- 8475286 TI - Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. AB - To define altered metabolites in the brain of patients with probable Alzheimer disease (AD) of two brain regions, localized in vivo hydrogen-1 magnetic resonance (MR) spectroscopy was performed with a short echo time (30 msec) in 11 elderly patients and 10 healthy age-matched subjects. The patients had mild to moderate dementia, assessed with standard neuropsychological tests. Two abnormalities in the patients' cerebral cortex were defined: When compared with healthy subjects, the patients showed a 22% increase (P = .005) (approximately equal to 1.5 mmol/kg) in myo-inositol (MI) and an 11% decrease (P = .005) in residues of N-acetyl (NA), a putative neuronal marker. The elevation of MI in patients with mild to moderate AD suggests that abnormalities in the inositol polyphosphate messenger pathway occur early in the natural history of AD. The combination of high MI and low NA at examination with H-1 MR spectroscopy shows promise as an early diagnostic test for AD. PMID- 8475287 TI - Contrast-enhanced transcranial Doppler US with a new transpulmonary echo contrast agent based on saccharide microparticles. AB - The purpose of this first patient study (phase II) was to evaluate the clinical usefulness of a new echo contrast agent at transcranial Doppler ultrasonography (US). Twenty patients were selected from a group of 242 patients undergoing conventional transcranial Doppler US who had low (n = 18) or absent (n = 2) Doppler signals from the middle cerebral artery (MCA). The extent and duration of Doppler signal increase was measured in 30 MCAs and in 14 basilar arteries following the intravenous injection of a transpulmonary galactose microparticle suspension (SH U 508 A) at three concentrations (200, 300, and 400 mg/mL). Doppler waveform analysis became possible in 93% (28 of 30) of the MCAs following injection. The maximal increase in average Doppler signal intensity (11 dB at 200 mg/mL, 15 dB at 300 mg/mL, and 17 dB at 400 mg/mL) and the increase in average duration of the signal enhancement (163 seconds at 200 mg/mL, 219 seconds at 300 mg/mL, and 240 seconds at 400 mg/mL) depended on contrast agent concentration. Doppler waveform analysis became possible in 79% (11 of 14) of the basilar arteries. The intravenous injection of this new echo contrast agent markedly increases Doppler signal intensity in patients with nondiagnostic results at conventional Doppler US. PMID- 8475288 TI - Sacral meningeal cysts: evaluation with MR imaging. AB - It is often difficult for the radiologist to determine if a given sacral meningeal cyst is causing symptoms. Radiographic criteria for identifying cysts likely to be symptomatic are needed. Using conventional magnetic resonance (MR) imaging along with a specifically designed flow-sensitive sequence, the authors characterized 24 cysts (19 patients) with respect to diameter and communication with the subarachnoid space. They found no significant difference in size between symptomatic and asymptomatic cysts (P > .05) but did observe a clear-cut disparity in the context of communication: Five of five asymptomatic cysts were shown to communicate on MR flow studies, while seven of seven symptomatic cysts were not shown to communicate. The authors propose that flow-sensitive MR imaging is useful in differentiating communicating from noncommunicating sacral meningeal cysts and that this information may be of value in classifying these lesions as more or less likely to be symptomatic. PMID- 8475289 TI - Cerebral perfusion in children: detection with dynamic contrast-enhanced T2* weighted MR images. AB - Cerebral perfusion dynamics were assessed with dynamic contrast material-enhanced T2*-weighted magnetic resonance (MR) imaging in 33 subjects aged 3-20 years. Group A (n = 20) had sickle cell anemia without clinical evidence of cerebrovascular disease. Group B (n = 13) consisted of 12 patients with cerebrovascular disease and homozygous sickle cell anemia and one patient without that anemia. All subjects underwent conventional MR imaging and a dynamic study in which a spoiled gradient-echo pulse sequence was used to generate images (acquisition time, 2.5 seconds) during injection of a compact bolus of gadopentetate dimeglumine (0.1 mmol/kg). For qualitative analysis, the dynamic images were displayed in cine mode. Group A demonstrated symmetric sequential region patterns of loss of signal intensity within 10 seconds of injection. Group B exhibited signal loss asymmetries that corresponded to cerebrovascular lesions on conventional MR images. Quantitative analysis enabled estimation of hemodynamic parameters, including relative cerebral blood volume, relative cerebral blood flow, and mean transit time. This method of assessment of cerebral perfusion dynamics complements conventional MR imaging. PMID- 8475290 TI - Joint effusion in children with an irritable hip: US diagnosis and aspiration. AB - Ninety-six children with an irritable hip possibly representing septic arthritis underwent clinical and laboratory evaluation, radiography, and ultrasonography (US). Forty had normal US scans; none were later shown to have septic arthritis, although three had osteomyelitis. Fifty-six children had effusion at US. Thirty one of these underwent US-guided aspiration, two unsuccessfully. On the basis of results of aspirate analysis, 15 of these 31 patients underwent surgical drainage, and septic arthritis was diagnosed in all 15. The mean peripheral white blood cell (WBC) count was not significantly higher in patients with septic arthritis (n = 21) than in patients with toxic synovitis (n = 24) (P = .44). However, the erythrocyte sedimentation rate and synovial fluid WBC count were significantly greater in those with septic arthritis than in those with toxic synovitis (P = .002 and P < .0001, respectively). Clinical evaluation, radiographs, and sonograms together determined the need for US-guided aspiration. US-guided aspiration allowed selection of only those with septic arthritis for operative drainage and shortened that procedure. Negative sonograms allow exclusion of septic arthritis but not osteomyelitis. PMID- 8475291 TI - "Recall" pneumonitis: adriamycin potentiation of radiation pneumonitis in two children. AB - The radiographic findings in two children with acute "recall" pneumonitis, associated with administration of Adriamycin (doxorubicin hydrochloride) and actinomycin D at variable intervals after local radiation therapy, were presented to emphasize the unique radiographic appearance and clinical course. A 10-year old girl underwent radiation therapy 9 weeks after completing an initial cycle of chemotherapy. Within hours of the resumption of chemotherapy, she was in clinical respiratory distress. Chest radiography showed a well-defined area of alveolar consolidation in the periphery of the right lung corresponding to the area of radiation. Shortness of breath and right chest rales developed in a 15-year-old boy within 12 hours of the resumption of chemotherapy 6 weeks after radiation therapy was completed. Chest radiography showed an alveolar infiltrate extending from the apex to the base of the right lung corresponding to the area of radiation. Symptoms may be confused with an infectious pathogenesis; thus, knowledge of the history of radiation therapy and the radiation port is important in initiating treatment with steroids rather than antibiotics. PMID- 8475292 TI - Prospective evaluation of patients with suspected hip fracture and indeterminate radiographs: use of T1-weighted MR images. AB - To assess the diagnostic efficacy of T1-weighted magnetic resonance (MR) images when findings on radiographs of the hip are indeterminate, 20 patients with suspected hip fracture and indeterminate radiographs were prospectively evaluated. MR imaging was performed with surface coil technique; one coronal T1 weighted (repetition time msec/echo time msec = 400/19) MR image was obtained. The total charge for the examination was $448 (compared with the following usual charges: radionuclide bone scan, $455; tomography, $299; and computed tomography, $797). When MR imaging and clinical outcome were used as the standard of reference, the prospective accuracy of MR imaging in diagnosis of the presence or absence of hip fracture was 100% (20 correct diagnoses). All MR studies were diagnostic. Of the 13 patients with fracture (eight with trochanteric and five with subcapital fracture), 10 patients (77%) underwent surgery and three patients (23%) received conservative treatment. T1-weighted MR images can enable diagnosis or exclusion of hip fracture whenever radiographs are indeterminate. The imaging time is approximately 7 minutes, and the cost of the examination can be made competitive with costs of other advanced imaging examinations. PMID- 8475293 TI - Abnormalities of articular cartilage in the knee: analysis of available MR techniques. AB - In an attempt to improve the detection of chondral abnormalities with magnetic resonance imaging, a fat-suppressed three-dimensional gradient-recalled acquisition in the steady state (GRASS) and spoiled GRASS (SPGR) sequence was optimized by study of five cadaveric knee specimens. Results with this optimized sequence then were compared with results with three spin-echo (T1-, proton density-, and T2-weighted) and two three-dimensional gradient-recalled echo sequences (GRASS and non-fat-suppressed SPGR) in the assessment of naturally occurring abnormalities of the patellofemoral compartment in 10 cadaveric knees. Results with the optimized fat-suppressed SPGR sequence were significantly better (P < .02) than results with the other five sequences and had a sensitivity of 96%, a specificity of 95%, and an accuracy of 95%. In addition, normal cartilage consistently appeared as a trilaminar structure with the fat-suppressed SPGR sequence, a feature that appeared to help in identification of chondral lesions. PMID- 8475294 TI - Hooked acromion: prevalence on MR images of painful shoulders. AB - An association between the morphology of the acromion and the occurrence of rotator cuff tear (RCT) has been suggested by findings at both pathologic examination and routine radiography. As a tomographic technique, magnetic resonance (MR) assessment of acromial shape may be more accurate than routine radiography. The authors studied acromial morphology on sagittal oblique MR images of a control population (47 shoulders), of patients with isolated impingement (30 shoulders), and of patients with full-thickness RCTs (34 shoulders) to assess the association of acromial shape with disorders of the rotator cuff. Acromions were classified as flat (type 1), smoothly curved (type 2), or hooked (type 3). Data were collected by two observers, blinded to clinical and surgical information, who acted in consensus. Patients with RCT had a significantly increased prevalence of type 3 acromions compared with control patients (62% vs 13%, P < .001). Type 3 acromions tended to be more prevalent in the group with impingement (30%, P = .17). There was no significant difference in the distribution of acromion types among control patients with respect to age or gender. PMID- 8475295 TI - Intravertebral vacuum cleft: changes in content after supine positioning. AB - Sequential radiographic and magnetic resonance (MR) imaging examinations were performed in nine patients with an intravertebral vacuum cleft indicative of avascular necrosis. Progressive changes in the content of the cleft occurred within an hour after the patients were placed in a supine position. Initially, the cleft showed a gaslike pattern during extension of the spine, with a radiolucent band on radiographs and a signal void on MR images. Later, the vacuum phenomenon disappeared on radiographs, and a fluidlike high-signal-intensity pattern appeared on T2- or T2*-weighted MR images, suggestive of a slow fluid inflow within the intravertebral cleft. Because the recognition of a vacuum cleft in a collapsed vertebral body helps avoid confusion with malignancy or infection, it is important to search for this in examinations performed immediately after supine positioning. PMID- 8475296 TI - Multicentric fibromatosis with metaphyseal dysplasia. AB - A new association between multicentric fibromatosis and a bone dysplasia is reported. Three patients are described, each of whom had multicentric fibromatosis of the lower extremity and a skeletal dysplasia. One of the patients had dysplastic changes restricted to the involved extremity. The other two had dysplastic changes of all the long bones. The dysplasia consisted predominantly of undertubulation reminiscent of the findings seen in Pyle disease. No clinical or radiographic abnormalities of the marrow were found in any of these patients. It is believed that this association represents mesenchyme that is predisposed to develop both dysplastic bone changes and tumor. PMID- 8475297 TI - MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. AB - An investigative study was undertaken to determine the potential for a new magnetic resonance (MR) imaging technique, RODEO (rotating delivery of excitation off resonance), for use as a diagnostic imaging tool for the breast. The RODEO technique provides fat suppression with T1 weighting and is ideal for gadolinium enhanced breast imaging. It is a short repetition time, steady-state sequence for high-resolution three-dimensional acquisitions and provides a clinically efficient imaging time of approximately 5 minutes for 128 sections. Imaging findings were correlated with serially sectioned pathologic specimens in 30 breasts with 47 malignant and 27 benign lesions. MR imaging had a sensitivity of 94% and a specificity of 37%. MR imaging depicted additional cancers not seen at mammography in 11 of the 30 patients (37%). The lesions not seen at mammography varied in size from 3 mm to 12 cm. RODEO MR imaging may be used to improve diagnosis of breast cancer in patients with mammographically dense breasts or silicone implants/injections and to stage disease in patients who are candidates for lumpectomy. PMID- 8475298 TI - Preoperative needle localization in the breast: utility of local anesthesia. AB - Eighty-nine consecutive patients undergoing needle localization at two facilities were alternately assigned to "local-anesthesia" (n = 46) and "no-local anesthesia" (n = 43) groups. Those in the local-anesthesia group received 1-2 mL lidocaine hydrochloride 1% subcutaneously at the expected site of insertion of the localizing needle. All patients were asked to rate the level of pain they experienced from the procedure as a whole by using a 10-cm horizontal visual analog pain scale. Data about patient age, menopausal and menstrual status, average daily caffeine intake, and whether the patients considered mammography to be a painful procedure were collected. Patients who did not receive local anesthesia had a lower mean pain score (2.52) than those who did (3.27, P = .18). Premenopausal patients in the second half of their menstrual cycle at the time of the procedure had a significantly higher pain score than those in the first half (3.54 vs. 1.70, P = .05). Patients who considered mammography a painful procedure reported a higher level of pain than those who did not (3.79 vs 2.38, P = .012). There was no relationship between age, caffeine intake, or menopausal status and pain experienced. PMID- 8475299 TI - US-guided automated large-core breast biopsy. AB - To evaluate the efficacy of ultrasound (US)-guided automated large-core percutaneous needle breast biopsy, biopsy of 181 ultrasonographically suspicious breast lesions was performed by using a long-throw biopsy gun and 14-gauge needles with continuous US guidance. A "freehand" technique with either 5.0- or 7.5-MHz linear-array transducers was used. Needle core diagnoses were compared with surgical diagnoses in the 49 lesions subsequently surgically excised. The remaining 132 cases were followed for 12-36 months. Agreement between needle-core and surgical diagnoses in the 49 lesions was 100%. This group included 34 cancers (28 infiltrating ductal, two mucinous, one mixed infiltrating ductal and lobular, and one each of intraductal, infiltrating lobular, and tubular carcinoma). To date, no cancers have been found in the other 132 cases. The procedure time averaged 20 minutes, and no complications occurred. With an accuracy approaching that of excisional biopsy, US-guided needle core biopsy provides an alternative to surgery. PMID- 8475300 TI - Pulmonary nodules: detection with thick-section spiral CT versus conventional CT. AB - Spiral volumetric computed tomography (CT) with single breath-hold technique was compared with conventional sequential CT in 39 patients. The spiral CT protocol consisted of a 10 mm/sec table feed during a 24-second breath hold at 145 mA, with reconstruction of images at 10-mm intervals; one (n = 21) or two (n = 18) sequences were necessary to screen the complete lung. Conventional CT was performed with a 1-second scan time, 145 mA, and contiguous 10-mm-thick sections. In the 39 patients studied with each technique, no lung nodule was detected in three, two had a single nodule, and 29 had multiple nodules. Two patients with normal findings at chest radiography and three with a solitary pulmonary nodule at conventional CT had multiple nodules at spiral CT. Mean number of nodules per patient was significantly higher with spiral versus conventional CT (18 +/- 4.5 vs 12.6 +/- 3.2 [mean +/- standard error of the mean], P = .01) as were the number of nodules less than 5 mm in diameter per patient (12.7 +/- 3.7 vs 8.4 +/- 2.3, P < .05) and 5-10 mm in diameter (2.9 +/- 0.9 vs 2.4 +/- 0.8, P < .05). Respiratory motion artifacts were never observed with spiral CT although they were present on four conventional CT scans. PMID- 8475301 TI - Improved parameters for unsharp mask filtering of digital chest radiographs. AB - Observer performance with four unsharp mask filtering algorithms for storage phosphor chest radiographs was compared with that with conventional screen-film radiographs in the detection of three types of simulated lung disease: nodules, fine lines, and micronodule clusters. Previously studied parameter sets (small [1.4-mm] and medium [5-mm] filter masks) and two new parameter sets (large [2.5 cm] and ultralarge [7-cm] masks) were compared by means of receiver operating characteristic analysis. With medium and small masks, nodule detection was inferior to that achieved with other modes. Use of ultralarge masks decreased the detection of lines compared with detection with conventional screen-film radiographs. Although detection of micronodule clusters was worse with digital images than with conventional screen-film radiographs, results with large and ultralarge masks were better than with small masks. Overall, filtering with large masks was best suited for simultaneously matching linear, nodular, and micronodular structures. These results suggest that lesion-specific processing of digital chest images is not necessary. PMID- 8475302 TI - Interpretation of subtle interstitial lung abnormalities: conventional versus storage phosphor radiography. AB - To evaluate the reliability of storage phosphor radiography (SR) in diagnosis of subtle interstitial lung abnormalities, the differences among radiologists in interpreting conventional screen-film radiographs and full-size and minified SR images obtained in 80 patients were studied. Forty patients had subtle interstitial lung abnormalities and 40 had no lung abnormalities. Seven chest radiologists and seven residents evaluated the images by using a five-point presence of abnormality scale. Results were evaluated with receiver operating characteristic technique. For all observers, no significant differences were observed among the three image types. For the chest radiologists, significant differences were observed between conventional radiographs and the two SR formats (P < .01). Furthermore, perceptual accuracy was best with conventional radiographs evaluated by chest radiologists. Overall performance with SR and conventional radiography was identical for diagnosis of abnormalities, but detection performance was significantly dependent on observer experience (P < .01 for chest radiologists and P > .01 for residents). For chest radiologists, critically important information may be lost with commercially available SR. PMID- 8475303 TI - Carcinomatous solitary pulmonary nodules: evaluation of the tumor-bronchi relationship with thin-section CT. AB - To investigate the value of computed tomography (CT) for depicting the relationship between carcinomatous solitary pulmonary nodules and the bronchial tree and predicting the results of various bronchoscopic biopsy techniques, the authors retrospectively reviewed CT scans from 27 consecutive patients with solitary pulmonary nodules associated with a positive bronchus sign. All patients underwent bronchoscopy and transbronchial biopsy. Macroscopic demonstration of the tumor-bronchi relationship was obtained in 18 patients. Five basic types of tumor-bronchus relationships were identified with CT: (a) bronchus cut off by the tumor, (b) bronchus contained within the tumor, (c) bronchus compressed by the tumor, (d) thickening and smooth narrowing of the bronchus leading to the tumor, and (e) thickening and irregular narrowing of the bronchus leading to the tumor. The diagnostic yield of transbronchial forceps biopsy and bronchial brushing was significantly higher in nodules characterized by a cut-off or contained bronchus. Transbronchial needle aspiration was performed in six patients, and results were positive in five, all of whom had a compressed or thickened bronchus. These results confirm that yield of transbronchial biopsy is determined by the type of tumor-bronchus relationship and the biopsy technique performed. PMID- 8475304 TI - Incomplete interlobar fissures: bronchovascular analysis with CT. AB - Thin-section computed tomographic scans of both lungs in 154 patients, including seven cadavers, with lung cancer (n = 37), diffuse (n = 32) or inflammatory (n = 30) lung disease, other proved or suspected disease (n = 23), or healthy lungs (n = 32) were analyzed to determine the frequency of incomplete interlobar fissure (IIF). An IIF was defined as a discontinuous linear shadow that remained in contact with the chest wall. An IIF was found in 128 of 154 right lungs (83.1%) and 77 of 154 left lungs (50.0%). Some bronchovascular structures crossed or passed through two contiguous lobes in the fused area. The most common bronchovascular structure associated with an IIF was a pulmonary vein; this association was found in 87 right lungs (56.5%) and 20 left lungs (13.0%). An IIF was traversed by a pulmonary artery in only seven right lungs and 13 left lungs or by a bronchus in only three lungs. It is concluded that recognition of an IIF might improve understanding of the spread of pulmonary disease. PMID- 8475305 TI - Retrograde catheterization of the ureter without cystoscopic assistance: preliminary experience. AB - Standard angiographic techniques were applied to fluoroscopically directed retrograde guide wire or catheter placement into the distal ureter without cystoscopic assistance. The procedure was successful in five of the seven initial attempts, with no complications. Retrograde pyelography and stent placement were accomplished for a benign posttraumatic ureteral stricture, a proximal ureteral calculus, and three malignant ureteral strictures. Percutaneous nephrostomy was obviated in all successful cases. Fluoroscopy time averaged less than 3 minutes. Mild intravenous sedation was used, and the procedure was well tolerated. This initial experience suggests that this method may be useful for a variety of endourologic procedures, as well as for routine retrograde pyelography. PMID- 8475306 TI - Placement of a wire mesh prosthesis in the external urinary sphincter of men with spinal cord injuries. AB - The authors report their experience with an intraurethral prosthetic stent as an alternative treatment for detrusor-external urethral sphincter dyssynergia (DESD). A sphincter prosthesis was inserted into the membranous urethra of 25 men with spinal cord injuries, DESD, and elevated voiding pressure. Bladder voiding pressure decreased from 87 cm H2O +/- 23 to 27 cm H2O +/- 11 in 12 months (P < .001). There was a significant decrease in residual urine volume 12 months after prosthesis placement, from 122 mL +/- 77 to 33 mL +/- 19 (P < .01); bladder capacity remained relatively unchanged, from 174 mL +/- 84 to 230 mL +/- 92 (P < .57). No deleterious effects were seen in renal or erectile function. Migration of three prostheses occurred 1 day to 6 weeks after insertion. One additional complication, pyelonephritis, occurred in a patient with preexisting vesicoureteral reflux, necessitating reimplantation of bilateral ureters. The intraurethral wire mesh prosthesis, with its simplicity of placement and minimal associated morbidity, offers a potential alternative to external sphincterotomy. PMID- 8475307 TI - Transurethral balloon dilation of the external urinary sphincter: effectiveness in spinal cord-injured men with detrusor-external urethral sphincter dyssynergia. AB - The authors investigated balloon dilation as a minimally invasive alternative to transurethral external sphincterotomy for the treatment of detrusor-external urethral sphincter dyssynergia (DESD). Seventeen spinal cord-injured men with voiding pressures greater than 60 cm H2O underwent balloon dilation of the external sphincter to 90 F at 4 atm of pressure for 10 minutes. The mean voiding pressures before and 12 months after dilation were 83 cm H2O +/- 35 and 37 cm H2O +/- 15, respectively (P = .008). There was a significant decrease in residual urine volume, from 163 mL +/- 162 to 68 mL +/- 59 (P = .05), whereas bladder capacity remained relatively unchanged at 253 mL +/- 181 and 230 mL +/- 97 (P = .30). Complications included one case of postoperative bleeding necessitating transfusion, two treatment failures, and one bulbous urethral stricture. Fourteen of the 17 patients (82%) now void without the aid of an indwelling catheter or alternative therapy. Balloon dilation has no detrimental effect on erectile function and may improve fertility. PMID- 8475308 TI - Abnormal renovascular impedance in patients with hepatic cirrhosis: detection with duplex US. AB - The purpose of this study was to determine whether duplex ultrasound (US) can allow detection of early impairment of renal function in patients with hepatic cirrhosis. The authors calculated the pulsatility index (PI) and resistive index (RI) by using duplex US in 17 patients with cirrhosis and ascites but with normal renal function (group A), in 16 patients with cirrhosis but no ascites (group B), in 20 with chronic hepatitis (group C), in six with peritoneal carcinomatosis (group D), and in 16 healthy control subjects (group E). All patients had normal renal function on the basis of blood urea nitrogen and serum creatinine values. PI and RI were higher (P < .001) in group A patients than in others. Cirrhotic patients with ascites had renal vasoconstriction even in the absence of clinically apparent renal impairment and full-blown hepatorenal syndrome. Impaired renal perfusion plays a key role in sodium and fluid accumulation in patients with liver disease. On the basis of these results, duplex US is useful in pathophysiologic and clinical studies in such patients. PMID- 8475309 TI - Interpretation of CT studies: single-screen workstation versus film alternator. AB - A prototype single-screen workstation with a 2,048 x 2,560-pixel high-brightness monitor, 0.11-second image display time, and simple ergonomic design was compared to a conventional horizontal film alternator in diagnostic interpretation of chest computed tomography (CT) studies. Four radiologists used either the workstation or film alternator in interpretation of studies obtained in 10 patients. A counterbalanced within-subject repeated measures experimental design was used. Response times were analyzed for both methods of interpretation. Grades of excellent, acceptable, and unacceptable were assigned by a blinded "grader" to reports of the radiologists. The average time needed for an interpretation at the workstation was 5.65 minutes. No interpretations were graded unacceptable. Retrospective power analysis showed that 16 observers rather than four would have been required to show that use of the workstation was faster than the alternator. With this 95% confidence interval, the workstation interpretation time is clinically equivalent to that with the alternator. These data show that this type of workstation has practical application in interpretation of CT, magnetic resonance imaging, and ultrasound studies. PMID- 8475310 TI - Crohn disease: prone-angled compression view in radiographic evaluation. AB - A prone-angled compression radiographic view was compared with traditional radiographs in 17 patients with suspected Crohn disease. The angled view was clearly superior to the posteroanterior view in visualization of disease in the terminal ileum and small bowel and was superior to spot radiographs in six of 10 patients with disease in the small bowel. This view can be a valuable adjunct when small bowel loops overlap in the pelvic area. PMID- 8475311 TI - A complication involving a braided hook-wire localization device. AB - At the authors' institution, needle localization of breast lesions with a braided hook wire involves the wire being cut 1-2 cm from the point of entry before dissection, to avoid contamination of the sterile field with the nonsterile portion of wire. During dissection, the wire is brought through the skin into the area of dissection. In one patient, fragments of wire filaments were left within the breast. Braided hook wires must be cut cleanly, the cut surface should be wiped before dissection, and the surgical area should be cleansed before closure. PMID- 8475312 TI - Cine scintigraphy for gastrointestinal bleeding. PMID- 8475313 TI - Is it possible to diagnose a tear at arthrography or MR imaging? PMID- 8475314 TI - Guide-wire-directed detachable balloons. PMID- 8475315 TI - Identification of atypical skin calcifications. PMID- 8475316 TI - Pharmacokinetic aspects of antidepressant treatment in the elderly. AB - 1. Physiological and metabolic changes with ageing may affect the pharmacokinetics of antidepressant drugs. 2. Pharmacokinetic parameters following single doses of antidepressants in the elderly tend to be altered compared with younger subjects. 3. Elimination half-life tends to be prolonged for most antidepressant drugs in the elderly due to decreased clearance and increased volume of distribution. 4. Steady-state plasma concentrations tend to be increased in elderly patients. 5. Inter-individual differences usually account for the majority of the variance in kinetic parameters rather than an effect of ageing per se. 6. The increased propensity for side effects in the elderly is probably due to pharmacodynamic rather than pharmacokinetic alterations with age. PMID- 8475317 TI - Genetic models in the study of alcoholism and substance abuse mechanisms. AB - 1. Vulnerability to substance abuse is an important emerging issue. Some related factors are the relationship between propensity to self-administer a drug and neurosensitivity to that drug; similarities and differences between various models of drug seeking behavior; and the commonality of drug-seeking behavior across drugs and genotypes, that is, whether reinforcement from and abuse of alcohol and other drugs define variations within a single behavioral phenomenon, or whether reinforcement and abuse must be individually defined for each substance involved. 2. Findings related to these issues are now being obtained from the areas of pharmacogenetics and operant drug self-administration. 3. The results indicate that reinforcement from alcohol and other drugs is only moderately related to preference for alcohol and other drugs. In addition, neurosensitivity to drugs appears to have little influence on whether that drug will come to serve as a positive reinforcer for any given individual or animal. Indeed, the critical factor appears to be the individual organism's innate propensity to find a particular drug reinforcing. 4. Initial findings also show that genotypic patterns of reinforcement from ethanol appear to correlate highly with patterns of reinforcement from cocaine and opiates. 5. From these findings it is concluded that there exist important genetic determinants of drug reinforced behavior; reinforcement is an important and independent effect of several psychoactive drugs; and drug seeking behaviors maintained by ethanol, cocaine and opiates may have at least some common biological determinants. PMID- 8475318 TI - Digital period analysis of EEG in depression: periodicity, coherence, and interhemispheric relationships during sleep. AB - 1. Interhemispheric EEG differences were compared between 12 symptomatic depressed outpatients, 12 asymptomatic patients and 12 normal controls during two consecutive nights in the Sleep Study Unit. 2. EEG was quantified using digital period analysis (DPA), a time-domain analysis of successive polarity changes (zero-cross) and instances of zero slope (first derivative), yielding percent time in each frequency band. 3. The degree of hemispheric asymmetry (L-R) was computed for delta, beta and theta percentages from REM, Stage 2 and Slow-Wave (SW) sleep. 4. Normals showed small asymmetries throughout sleep with largest differences in SW, with no consistent relationship between right and left activity and sleep stage. 5. Both depressed groups showed largest asymmetries in REM sleep, with significantly more beta, theta and delta in the right hemisphere consistently. None of the 24 depressed patients showed greater left hemisphere activity throughout sleep. PMID- 8475319 TI - 3H-spiperone binding capacity in mononuclear cells: a family study. AB - 1. A family study was carried out using a putative biological vulnerability trait in families of schizophrenics and schizoaffective indexprobands to investigate, if the clinical phenotype and a biological marker for schizophrenia are cosegregating within families. 2. The binding capacity of the dopamine antagonist spiperone to mononuclear cells was investigated in 21 indexprobands and a total of 147 first and second degree relatives. 3. Increased binding capacity could be found in 17 indexprobands and in their affected relatives, independently from clinical diagnosis and in 22% of their normal relatives. 4. No increased binding capacity was found in 4 indexprobands and in their affected relatives and not n any of the unaffected relatives. These results indicate, that increased spiperone binding may cosegregate with the risk for functional psychoses and that families, loaded with psychiatric disturbances may be distinguished on a biological basis. PMID- 8475320 TI - Interleukin-1 alpha and interleukin-2 in cerebrospinal fluid of schizophrenic subjects. AB - 1. It has been postulated that the interrelated processes of neurodegeneration, neuroplasticity, and neuroimmunological abnormalities may play a role in the pathophysiology of schizophrenia. Since, interleukins are produced in the central nervous system and have cytokine and growth promoting properties, they are an obvious choice to consider in these neural processes. 2. Cerebrospinal fluid obtained from schizophrenic patients, on and off medications, and from normal controls was assayed for interleukin-1 alpha (IL-1 alpha) and interleukin-2 (IL 2) using a sensitive enzyme-linked immunoassay. 3. IL-1 alpha concentration were below the detection limits of the assay in both controls and schizophrenics. 4. IL-2 levels were under 1 ng/ml CSF in nearly all subjects. There was no significant difference in IL-2 levels between medicated and medication-free schizophrenics or when patients were compared to controls. PMID- 8475321 TI - Abnormal lateralization in finger tapping and overt aggressive behavior. AB - 1. The relationship between abnormal cerebral lateralization and overt aggressive behavior was examined in 41 violent psychiatric patients in a maximum-security hospital. 2. Cerebral lateralization was measured using the Finger Oscillation Test from the Halstead-Reitan Neuropsychological Battery, and aggressive behavior was measured during a six-month period of hospitalization using the Overt Aggression Scale. 3. Patients with the most abnormal pattern of lateralization exhibited the highest frequency as well as the highest severity of overt aggressive behavior. This pattern could not be explained by the influence of age, race, IQ, history of head trauma, brain damage, or psychiatric diagnosis. History of seizures, alcohol abuse, and drug abuse, however, were found to be intervening variables in the lateralization-aggression link. Once their influence was removed using analysis of covariance, there was no relationship between lateralization and aggression. 4. The results suggest that it is unlikely that there is a direct causal relationship between abnormal lateralization and aggressive behavior. PMID- 8475322 TI - Amnestic effects of triazolam and other hypnotics. AB - 1. The effects of a number of hypnotics were compared to a range of results collected for triazolam on objective measures of CNS sedation (critical flicker fusion) and short-term memory function (memory scanning). 2. Assessments taken after the drugs had been administered but prior to the onset of sleep showed that in comparison to placebo most of the compounds were effective sedatives and this correlated highly (r = 0.734, p < 0.04) with amnestic effects found at the same time, suggesting that general CNS sedation is a major component of anterograde amnesia. 3. Residual effects assessed the morning after the hypnotics had been used showed a similar relationship (r = 0.896, p < 0.005). 4. The distribution of results indicates that 0.25 mg triazolam has an acute amnestic profile which is similar to other hypnotics, but possesses a distinct lack of residual effects. PMID- 8475323 TI - The detection of age-related decrease of dopamine D1, D2 and serotonin 5-HT2 receptors in living human brain. AB - 1. Using positron emission tomography and 11C-N-methylspiperone and 11C- SCH23390, dopamine D1 and D2 receptors, and serotonin 5-HT2 receptors in human brain were evaluated in living healthy age different subjects. 2. Dynamic analysis of PET data indicated that these receptor binding abilities decreased with aging in healthy humans. PMID- 8475324 TI - Alprazolam in panic disorder: a retrospective analysis. AB - 1. The charts of 78 panic disorder outpatients treated with alprazolam (mean dose 4.30 mg/day, mean duration 31.9 months) were reviewed for demographics, past history (including substance abuse and major depression), and evidence of alprazolam abuse. In addition, the patients were evaluated by Clinical Global Index for improvement at last contact. 2. Moderate to significant recovery was found in 77% of patients. Major depression was seen in 41%. Depressed patients were more likely to have coexisting agoraphobia and a past history of alcohol abuse than non-depressives. 3. There was no DSM-III-R anxiolytic abuse, but 12% showed unauthorized use of the alprazolam. These subjects were three times more likely to have a history of drug abuse than non-misusers. 4. These results indicate that alprazolam is effective in the long-term treatment of panic disorder, but that prolonged management may be required. Further, the data raise concerns about use in panic patients with substance abuse histories. PMID- 8475325 TI - Relation between long-lasting amounts of excitatory amino acid and its neuronal uptake system in cultured cerebellar granule cells under hypoglycemia. AB - 1. Basal release of amino acids (Glu, Gln, Gly and Tau) in cultures of rat cerebellar granule cells was detected at 3 days in vitro (DIV). The amounts of Gln and Gly released increased according to days of culture. Moreover, the amounts of Glu in a glia poor culture of granule cells tended to be higher than those in glia rich cultured cells, while Gln, Gly and Tau concentrations were lower in glia poor cells than in glia rich cells. 2. After depolarization induced by high KCl, amounts of all measured amino acids significantly rose to more than 1.5 times their basal values. The increased values obtained in a glia rich culture of granule cells were higher than those in a glia poor culture of cells throughout all cultured days. 3. Under deprivation of glucose, most concentrations of amino acids in the medium, especially Gln concentration, increased by 50 mM KCl were lower than those seen under normal conditions. Such lesser efflux examined under hypoglycemia was much more clearly recognized in glia rich cultures than in glia poor cultures. However, the amounts of Glu at 10 and 14 DIV, and also Gly and Tau amounts at 10 DIV were significantly higher than those seen in the cultures of glia poor cells under normal conditions. 4. The dosage of 10 microM Glu-induced [Ca2+]i accumulation was inhibited by several different types of Ca antagonists and scopolamine. Meanwhile, the dosages of the tested drugs, except for scopolamine, required for blocking Glu-induced [Ca2+]i accumulation under hypoglycemia were less than those required under normal conditions. These results suggest that neuronal death induced hypoglycemia might be caused by the dysfunction of the neuronal, but not glial, Glu uptake system, and that some Ca antagonists might be useful in preventing the neuronal death caused by hypoglycemia. PMID- 8475326 TI - Effects of thyroid state on preference for and sensitivity to ethanol in Fischer 344 rats. AB - 1. It has been reported by several groups that thyroid status can alter ethanol preference in rats. However, results using different methods and different strains of rats have not been consistent. 2. In this study, thyroidectomy or T4 augmentation was used to produce hypothyroidism or hyperthyroidism, respectively, in adult male Fischer-344 rats. 3. Preference for weak solutions (4 or 5%) of ethanol or tap water and ethanol-induced sedation and hypothermia were compared in hypothyroid, hyperthyroid and euthyroid rats. 4. No significant differences in preference indices (the ratios of ethanol to total liquid consumed) among the three groups were observed; however, for ethanol to contribute a greater portion of total calories ingested by hypothyroid rats than by euthyroid or hyperthyroid rats. 5. The duration of sleep resulting from a single i.p. injection of 2.5 mg/kg ethanol was increased (by 34%) in hyperthyroid rats and decreased (by 16%) in hypothyroid rats compared to euthyroid controls. Only the effect of hyperthyroidism was significant at the 0.05 level. 6. Colonic temperatures differed with thyroid state (hyperthyroid > euthyroid > hypothyroid) but the decrease produced by ethanol did not differ by thyroid state. 7. Observed differences in ethanol-induced sedation are consistent with differences in brain TRH levels and effects on neurotransmitter systems associated with different thyroid states. PMID- 8475327 TI - Use of Edinburgh Postnatal Depression Scale in a North American population. AB - 1. The authors mailed the Edinburgh Post-natal Depression Scale to 308 women at six weeks postpartum. 2. It was completed and return by 185 women (60.0%). 3. Thirty-two of them (17.4%) scored 12 and above, the threshold reported to identify most women with postpartum depressive disorder. PMID- 8475328 TI - [Structure and expression of actin genes]. PMID- 8475329 TI - [Construction of helical structure by lipids and related compounds]. PMID- 8475330 TI - [Observation of biological materials by STM/AFM--principles and present status of applications]. PMID- 8475331 TI - [Antisense strategies come of age]. PMID- 8475332 TI - [A protease having a lectin-like domain: structure and function of rarobacter protease I, a yeast-lytic enzyme]. PMID- 8475333 TI - [Detection of RNA packaging signal of HIV-1 and its application for a novel AIDS therapy]. PMID- 8475334 TI - [Colorectal cancer. A study of 133 surgical cases]. AB - The author studied the medical records of 133 patients who underwent surgery for adenocarcinoma of the colon or rectum in the Metropolitan Hospital Complex Arnulfo Arias Madrid from June 1972 to July 1992. In 9 (6.7%) the tumor was staged as Dukes A, in 49 (36.8%) as Dukes B; in 60 (43.1%) as Dukes C and in 10 (16.7%) as Dukes D. The anatomical location of the tumor was the cecum in 9 (6.7%), the ascending colon in 3 (2.3%), the sigmoid colon in 44 (33%) and the rectum in 41 (31.6%). Of the rectal carcinomas 24 (58.5%) were in the inferior one third, 10 (24.3) were in the middle and 7 (17%) in the superior third. It is evident that nearly two thirds of the tumors were within reach of the digital rectal examination of the sigmoidoscopic examination. The parents ranged from 21 to 89 years of age and their median age was 63 years. 73 patients were women and 60 were men. 60.5% of the women and 39.5% of the men had carcinoma of the colon. The sexual prevalence of carcinoma of the rectum was different: 5% were in men and 43% were in women. 2.2% of the tumors were synchronous and 4% were metachronous. The author discusses the number, type and indications for the surgical procedures used. There were no perioperative deaths. The 5 year survival for adenocarcinomas of the colon was 100% for those patients with tumors staged as Dukes A, 78.5% for the Dukes B, 61.1% for the Dukes C and 0% for those staged as Dukes D. For the rectal adenocarcinomas the 5 year survival was 100% for those patients with tumors in Stage Dukes A, 57.1%, for those in Dukes B, 33.3 for those in Dukes C and 0% in those in Dukes D. These results indicate that these patients are seen in an advanced stage and point to the urgent need to make the diagnosis in early, curable stages. The low incidence of tumors in stage Dukes A indicates an indifference of the patients and/or the doctors to the symptoms and signs of this disease. The most frequent symptoms, in descending order were: bleeding on defecation (all types), change in bowel habits (diarrhea or constipation), abdominal pains, tenesmus and anemia (with its different clinical manifestations). Other symptoms were a palapable abdominal mass, feces with bloody mucus and rectal prolapse on defecation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475335 TI - [10 years of nosocomial infections at the Santo Tomas Hospital]. AB - The incidence of nosocomial urinary tract infections (UTI) in the medical services of Santo Tomas Hospital from 1980 to 1985 was 56% in Neurology Section, 73% in cardiology and 74% in nephrology. These percentages declined, with epidemiological surveillance, to 21%, 31% and 53% respectively, for the period between 1986 and 1990. In the surgical services the incidence of nosocomial UTI was 85% in urology and 15% in general surgery, from 1980 to 1985. The incidence remained unchanged in urology (81%) and general surgery (17%) despite epidemiological surveillance, but decreased in neurosurgery (from 55% to 37%) for the period between 1986 and 1990. Between 1985 and 1990, Staphyloccocus aureus was the most frequently isolated bacterium from surgical wounds (34%) and from patients with intravenous catheters (23%). Pseudomonas aeruginosa was the most frequently isolated bacterium in nosocomial UTI (26%) and respiratory tract infections (45%) and in patients with nosocomial septicemia, it was a species of Klebsiella. PMID- 8475336 TI - [Familial calculous cholecystopathy]. AB - The history and laboratory examination of the parents of six families with a history of biliary showed that five mothers and one father had cholelithiasis. Two of the mothers also had exogenous obesity and diabetes mellitus, and one mother also had lipid abnormalities. Among the 21 children of the same families, one son had cholelithiasis; 5 children (4 women and one man) had cholelithiasis and exogenous obesity; 10 (9 women and one man) had cholelithiasis, exogenous obesity and diabetes mellitus; two (one man and one woman) had cholelithiasis, exogenous obesity and lipid abnormalities; one son had cholelithiasis and diabetes mellitus, and one son had cholelithiasis and lipid abnormality. Among the 18 grandchildren of these families, 3 (2 women and one man) had cholelithiasis; 5 granddaughters had cholelithiasis and exogenous obesity; 2 grandsons had cholelithiasis, exogenous obesity and diabetes mellitus; 2 grandsons had cholelithiasis and lipid abnormality; one grandson had cholelithiasis, diabetes mellitus and hyperuricemia; one grandson had cholelithiasis, exogenous obesity, lipid abnormalities and hyperuricemia, and one grandson had exogenous obesity and diabetes mellitus. Finally, of the greatgrandchildren, one girl had cholelithiasis. PMID- 8475337 TI - [Evaluation of 4 immunobiochemical/molecular methods for the identification of Trypanosoma cruzi and Trypanosoma rangeli strains]. AB - In American man can be infected with two trypanosomes: Trypanosoma cruzi, the etiological agent of Chagas' disease and Trypanosoma rangeli, a suspected nonpathogenic parasite. In this communication are presented 4 methods in order to improve the current knowledge about the specific identification of these parasites. Using the SDS-PAGE technique it was possible to differentiate between T. rangeli. and T. cruzi based in at less 4 protein bands with a relative molecular weights of 93, 77-73, 63 and 54-52 KDa. These polypeptides were found only in T. rangeli electrophoretic profiles. An ELISA test showed that the antigenic composition found in the enzyme cisteine proteinase (cruzipain) is specific for T. cruzi epimastigotes. Antigenic analysis by Western blot assay, proved that T. rangeli and not T. cruzi present antigenic bands with a Mr of 142, 63, 54, 51, 49, 43, 39 and 24 KDa. Finally, using the Southern blot procedure, it was confirmed that SAPA, a DNA sequence originally identified in the T. cruzi, genome, is absent in T. rangeli nuclear DNA. These initial observations revealed that it is possible to identify both parasites using the described methods, however further works are required to clarify the biochemical, immunological and molecular relationship between T. rangeli and T. cruzi. PMID- 8475338 TI - [Choledochal cysts. Review and presentation of 2 girls with perforated cyst]. AB - The clinical record is reported of two female girls, 4 1/2 and 5 1/2 years old, who were reported in 1988 at the Children's Hospital in this City with diagnosis of perforated Cholodochal supurated cyst and who were asymptomatic when they left the hospital. It is mentioned that another four patients had been operated in the same hospital, between 1981 and 1987, with choledochal cyst diagnosis. PMID- 8475339 TI - [Bioessay with brine Artemia to predict antibacterial and pharmacologic activity]. AB - The Brine Shrimp Test (BST) is a simple and inexpensive method to test cytotoxity, to biodirect phytochemical fractionation of natural products and as a predictor for antitumor and pesticidal activity. In this work, the BST test, an antibacterial test and the rat hippocratic screening test were used on 25 plant extracts and fractions, to evaluate the correlation, if any, between the BST and the others. Preliminary results show that the BST is not a predictor of antibacterial activity nor the hippocratic screening test. PMID- 8475340 TI - [First report in Panama on Nerocila californica Schioedte and Meinert 1881 (Isopoda: Cymothoidea) in Sciaenops ocellatus (L) (Pisces: Sciaenidae)]. AB - One juvenile specimen of the isopod Nerocila californica (acuminata form) was found on the skin of a cage-raised red drum, Sciaenops ocellatus, in Aguadulce, Cocle Province. This finding is the first report of the occurrence of Nerocila californica as ectoparasitic of fishes on the Pacific side of the Republic of Panama. PMID- 8475341 TI - [Vasovagal syncope: the value of tilt-table testing in the evaluation of loss of consciousness]. AB - Syncope, an eminently frequent syndrome, has multiple and varied causes. Its diagnosis is important in view of the poor prognosis of cardiac syncopes and also of the morbidity and discomfort associated with the other etiologies. Unfortunately, the cause eludes us in half the patients so that a clear prognosis and effective therapy can be given to only a few patients. Tilt-table testing, alone or with isoproterenol, is now considered as a noninvasive, sensitive and specific method for identifying patients predisposed to vaso-vagal syncope, a major cause of syncope of unknown origin. Tilt-table testing also helps in tracking many pathologies contributing to syncopes. In the absence of a universal treatment of vasovagal syncope, tilt-table testing has revealed itself as a contributory guide to the best possible treatment. PMID- 8475344 TI - [Linear opacities in the abdomen]. PMID- 8475343 TI - [Renal transplantation at the Free University of Brussels]. AB - From the data collected in 1,041 renal transplantations performed at the Universite Libre de Bruxelles between 1965 and 1992, the time-evolution of the results is described. At 5 year, patient's survival rate increased from 37% during the 1965-69 period to 95% since 1985 whereas total graft survival rate, which was only 13% during the 1965-69 period, reaches 65% at the present time. Among the factors responsible for the progress in the results since 1980, immunosuppressive therapy is the strongest: the best results are currently obtained by the use of triple therapy associating corticosteroids, azathioprine and cyclosporine, combined or not with the prophylactic administration of OKT3 monoclonal antibody. Future development of new immunosuppressive protocols, more specific and more potent, is emphasised, as well as the need to promote transplantation from a living related donor to meet the current shortage of organs. PMID- 8475342 TI - [Neonatal abstinence syndrome: current and future aspects]. AB - Pregnant heroin-addicted women constitute a major social problem that should not be ignored. Newborns may develop a neonatal abstinence syndrome (NAS). They present with behavioural troubles running a typical clinical course. The level of severity of NAS will be accurately determined, leading to definition of the most appropriate therapy. The best therapeutic formula appears to be paregoric elixir, mixed with phenobarbital if necessary. Least severe cases can be easily controlled by appropriate surrounding conditions. Pharmacological as well as physiopathological effects of opiates are described. Little is known about the long-term effects of opiate exposure; they apparently include frequent instrumental troubles. At the present time, the rapid intervention of a multidisciplinary team is recommended, taking charge of the mothers who should receive methadone in progressively tapering doses. PMID- 8475345 TI - [Erroneous parallels]. PMID- 8475346 TI - [The concept of ergotherapy: joint protection and remedial device]. AB - Joint protection is an important, unfortunately often neglected method of treatment for various rheumatological conditions. With theoretical and practical working methods, the occupational therapist conveys valuable information regarding the successful treatment of threatening joint deformity and efficient pain reduction. PMID- 8475347 TI - [Understanding of and coping possibilities in chronic rheumatoid arthritis in a family setting]. AB - Results of a Swiss study dealing with the coping potential of patients suffering from rheumatoid arthritis and their family members are presented. Patients and their families have their own understanding of rheumatic disease which must be respected by the physicians. Whereas women are prone to suffer in a passive manner, men more often tend to be more heroic. It is recommendable to counsel occasionally family members of rheumatic patients to diminish stress and to give precise informations to protect from over-responsibility. PMID- 8475348 TI - [Modern rheumatism surgery: prospects, hazards, results]. AB - The conservative management of rheumatoid arthritis (RA) the value of which is a symptomatic or at best a pathogenetic one, has failed to achieve a decisive breakthrough in the past 25 years. By contrast the orthopedic-surgical management of RA has proved able to rehabilitate patients who would otherwise gradually lose their independence. The close cooperation between rheumatologists and orthopedists in specific rheumatoid arthritis centers and the recruitment of specially trained therapeutic teams have boosted the recent progress in this field. However, the main responsibility for the patient continues to lie with the rheumatologist. Operative procedures are only considered when despite a well conducted conservative treatment signs of progressive articular destruction appear; they do not interrupt the conservative management, but are a completion of it. The art of the rheumatology-surgeon reveals itself in his ability to set up a clear-cut therapeutic plan with priorities. In particularly complex cases the indication will require a team discussion, which includes the occupational therapist who has previously assessed the patient's handicap in the performance of ADL and will be centered around the patient, whose motivation is of crucial importance to the success of our efforts. Throughout the many years of active practice and by performing thousands of operations--preventive (e. g. synovectomies) as well as reconstructive ones (e. g. arthroplasties)--we have gained a vast experience in different operative procedures, which we have come to divide into three categories. Whenever possible we start with an operation regarded as particularly promising, thus overcoming the patient's understandably reserved attitude towards surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475349 TI - [Value of physiotherapy in chronic rheumatoid arthritis]. AB - The main reasons for the importance of physiotherapy in treatment of rheumatoid arthritis are the biomechanical and neurophysiological factors, influencing not only joint function but also trophism. The dependence of the mechanical structural differentiation of all parts of the joint from the regular practical usage, which is clinically obvious and can be pathophysiologically explained, enables us to use successfully all types of functional therapies. The treatment principle of calisthenics and ergotherapy must always again be derived from the therapy-relevant principles of joint physiology: the requirement of normal joint sensory; physiological instability; continuous activity for nutrition and structural differentiation; taking into consideration receptor sensitization during arthralgia; therapeutic usage of regeneration potency within its limits; and to avoid the unphysiological of an arthritis. The sketchy presentation of the hand's biomechanic lets us recognize easily the generation and prophylactics of the most important deformities: the so-called zig-zag deformities--button hole, swan neck, scoliosis of the hand, the subluxation, particularly those towards palmar, and the radial deviation of the carpus. In praxis we are searching for stabile joint positions, and we try to avoid lax joint positions to transmit force; also we are looking for early recognition of subluxations resp. deformities to train the joints, to fight reflex-dystrophic after-pain, the usage of orthotic devices, and finally treatment resp. prophylactics of contractures. Also part of physiotherapy are supporting and accompanying passive physiotherapeutic measures, therapeutic sport and handling of chronic states of pain. The sense and importance of all three supporting each other therapeutic concepts, will also be pointed out. PMID- 8475350 TI - [Diagnosis and therapy of Lyme arthritis]. AB - Several distinct patterns of rheumatic manifestations can be seen throughout the course of Lyme borreliosis: intermittent and migratory musculoskeletal pain without objective findings, intermittent arthritis, chronic erosive arthritis, and joint deformities under affected skin in acrodermatitis chronica atrophicans. Commonly, Lyme arthritis is a late disease manifestation. A clinical history of extra-articular disease manifestations is the most reliable key to Lyme arthritis. However, arthritis often occurs without antecedent early-disease manifestations. The diagnostic significance of serological findings suggesting Lyme arthritis must be considered carefully with regard to the typical clinical features of Lyme arthritis and its potential differential diagnoses. Otherwise, Lyme arthritis will be frequently over-diagnosed. Lyme arthritis can be cured with antibiotics. However, treatment failures occur with any of the hitherto recommended regimens. PMID- 8475351 TI - [Acute-stage para- and tetraplegia]. AB - A quarter of a century ago, in October 1964, the first spinal cord injury center in Switzerland was opened at Geneva University Hospital. At that time all para- and tetraplegics were classified as "high-risk" patients. Early mortality, covering the initial four weeks following trauma, was still around 15%. The available resources for diagnostic assessment were limited to clinical examination and neuroradiological assessment (subsequently improved by the introduction of tomography and gas myelography). A great many patients suffered a deteriorated neurological level due to inadequate, multiple transfers between hospitals. Most patients who are paralyzed following a road-traffic accident show severe polytrauma. Their chances of survival and functional recovery have greatly improved in recent years due to efficient emergency transport by helicopter, admission to an intensive care unit (respiratory therapy, prophylactic anticoagulation, gastrointestinal cytoprotection, prevention of pressure sores, etc.) and a comprehensive medico-surgical team approach (orthopedic surgeons, neurosurgeons, ICU specialists, internists, etc.). Evaluation of the spine and spinal cord by NMR and CT scan allows precise assessment of the extent of CNS damage and provides additional guide-lines regarding efficient surgical reposition and spinal fusion. Ongoing experimental research in neurophysiology and neurobiochemistry of the brain and spinal cord is presently yielding some interesting results which hold out new hopes for functional recovery in some specific types of incomplete spinal cord trauma. PMID- 8475352 TI - Pathophysiological alterations in the central nervous system due to trauma. AB - Neurotrauma is the largest cause of death and severe disability in young adults. In this review, the pathophysiological processes which damage the brain and spinal cord, both acutely, and hours to days after injury, are discussed. Secondary, delayed damage is the major cause of bad outcome in at least 40% of patients, with severe head injury. Diffuse damage to axons, hypoxic-ischaemic damage to neurons and astrocytes, contusions, intracranial haematomas, and brain swelling are discussed. The prospect for improving outcome by pharmacological therapy, and the current status of head injury trials are presented. PMID- 8475353 TI - [Role of isotope methods in the evaluation of cardiac function in intensive care]. AB - Radioisotopic cardiac investigation techniques still have a limited role in intensive care units, mainly due to cumbersome traditional equipment, even if in some cases favourable local circumstances exist, such as the proximity of a nuclear medicine unit or the availability of a mobile gamma camera. Nevertheless, nuclear techniques show a number of interesting features, mainly related to the fact that measurements of cardiac chamber volumes and of their variations can be directly derived from activity counts, without any geometrical hypothesis as it is necessary for other methods such as contrast angiography or echocardiography. The whole cardiac cycle (its systolic part as well as its diastolic part) can therefore be evaluated. In addition, since the blood pool labelling remains stable for a long period after a single tracer injection, continuous monitoring of critically ill patients becomes possible. In this case it is no longer the gamma camera imaging system which may be used but rather a very sensitive miniature detector associated with a computerized data acquisition system, allowing beat-by-beat assessment of cardiac activity. The development of this device raises specific problems related to detection geometry, elimination of extracardiac background and stability of the probe positioning on the patient's thorax, but it is clear that such a system merits its place in an intensive care unit in the near future. PMID- 8475354 TI - Imaging strategies in the detection and evaluation of ARDS. AB - Considerable evidence has accumulated indicating that the chest radiograph is the most reliable imaging technique to evaluate the severity of lung edema in patients with established ARDS. Recently, the radiographic approach has been validated by direct comparison of an x-ray score of edema with the densitometric analysis of lung CT scan images. CT scanning may prove useful in quantitating the amount of residual healthy lung and in evaluating the effectiveness of PEEP in patients with acute respiratory failure. The application of CT scanning in these patients should be further expanded. Special effort should be made to evaluate unanesthetized, spontaneously breathing patients and to correlate CT quantitative data with the simultaneous analysis of portable chest radiographs in order to enhance the physician's ability to extract valuable, physiologic information from the chest film in critically ill patients. In order to improve the survival rate of patients with ARDS, methods are needed which detect ARDS at its earliest clinical stage. A number of radioisotopic techniques have been developed, based on the evaluation of the leakiness of the alveolar-capillary barrier either from the vascular or from the airspace side. Clearance of aerosolized DTPA from airspaces, although extremely sensitive, is not specific for ARDS in as much as factors other than lung injury may equally affect the rate of DTPA clearance from the lung. External detection of transvascular protein flux may serve as noninvasive means to assess the integrity of the lung microvascular endothelial barrier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475355 TI - [Imaging in blunt abdominal trauma]. AB - Sonography has largely replaced peritoneal lavage in the initial evaluation of blunt abdominal trauma. Computed tomography is the imaging modality of choice for further evaluation of hemodynamically stable patients. It can be used effectively to visualize multiple injuries in various anatomic regions in one single study. CT is particularly helpful in detecting intra- or retroperitoneal hemorrhage and in defining the extent of injuries to the spleen, the liver, and the kidneys. Traumatic injuries to the pancreas, bowel, and mesentery can be assessed. Angiography plays a major role in the diagnosis and therapeutic embolization of exsanguinating hemorrhage associated with pelvic fractures. PMID- 8475356 TI - Treatment of septic shock with antibodies to tumour necrosis factor. AB - The high mortality associated with septic shock has prompted intensive study of the pathophysiological basis of this syndrome in an effort to better understand the processes that lead to tissue injury. One important outcome of this work has been the recognition that the cytokine tumour necrosis factor (TNF) is an important mediator of endotoxin-induced lethality. Accordingly, studies were done which showed that antibodies to TNF could protect animals from death in a variety of model systems, and based on these findings, clinical studies were initiated. This paper reviews the present status of clinical trials of anti-TNF in sepsis. These antibodies appear to be safe, and preliminary experience suggests that they may be effective in some patients with the sepsis syndrome. A final assessment of efficacy must await the large, placebo-controlled trials that are now in progress. PMID- 8475357 TI - [Hemodynamic improvement during therapy using the intravascular oxygenator (IVOX)]. AB - The intravascular oxygenator (IVOX) is a new device which is implanted in the vena cava sup. and inf. where it oxygenates the blood and removes CO2. We report on its successful use in a young patient with severe pneumonia. This 21-year-old female was admitted to hospital with acute respiratory distress due to pneumococcal pneumonia and sepsis following chickenpox. Considering the rapidly progressive course with severe hypoxia and shock, PaO2/PaCO2 values of 6.5/6.4 kPa on mechanical ventilation with an FiO2 of 1.0 and a PEEP of 13 mbar, we decided to implant an intravascular oxygenator. Besides rapid improvement of oxygenation, we observed remarkable recovery of cardiovascular function such as an increase in mean arterial pressure and mixed-venous saturation, while the dose of vasopressors could be decreased. The intravascular oxygenator was removed without problems after 29 days of continuous use, when pulmonary function allowed an FiO2 of 0.45. The patient was discharged from the intensive care unit after 99 days in a good neurological and stable cardiovascular state. PMID- 8475358 TI - [Unexpectedly prolonged thrombin time]. AB - The thrombin time assay is able to detect abnormalities of the terminal phase of plasmatic coagulation. The differential diagnosis of thrombin time prolongation includes (1) inhibition of the added thrombin by exogenous heparin or endogenous heparin-like anticoagulant, seldom by acquired antibovine thrombin antibodies, (2) qualitative fibrinogen disorders (congenital and acquired dysfibrinogemia, (3) quantitative fibrinogen disorders (hypo- and afibrinogenemia), and (4) delayed fibrin polymerization due to fibrin/fibrinogen degradation products, paraproteins or seldom acquired antibodies against fibrinogen. PMID- 8475359 TI - [Closure of patent ductus arteriosus using interventional catheterization]. AB - Percutaneous closure of patent ductus arteriosus can be performed with the Rashkind technique. This procedure has been performed in 16 patients in Geneva since 1989. The age of the patients varied from 2 to 44 years (4 boys, 7 girls, and 5 women). Pulmonary hypertension was present in only 1 child. A 12 mm Rashkind umbrella was used in 11 patients with ductus of < or = 4 mm inner diameter, while a 17 mm umbrella was used in 5 cases for larger ducts. Ductus closure was carried out through a transvenous femoral approach in 15 cases, while in 1 patient a transarterial approach was employed because of impossibility of passing the ductus from the pulmonary artery. There was neither mortality nor morbidity in this series. The aortography performed just after device placement showed total ductus occlusion in 8 patients and partial closure in 8 others. The follow-up by color Doppler showed disappearance of the residual shunt in 4 of these 8 patients. Prophylaxis of bacterial endocarditis is therefore no longer necessary in 13 patients with complete ductus closure. Our experience with this technique confirms its efficacy and the possibility it offers of avoiding thoracotomy in the vast majority of patients with a patent ductus arteriosus. Further miniaturization of the device and delivery system should make it applicable in the neonatal period. PMID- 8475360 TI - [Long-term effect of amiodarone therapy following myocardial infarct in patients with complex ventricular arrhythmias]. AB - In the BASIS study, an improvement in 1 year survival of patients with asymptomatic complex ventricular arrhythmias with low-dose amiodarone was shown in comparison with an untreated control group. To assess whether this beneficial effect would last for a longer follow-up despite discontinuation of amiodarone therapy after one year, we assessed long-term survival and mode of death in the 91 survivors of the first year in the amiodarone treatment group and the 99 survivors in the control group by phone calls to private physicians, patients and hospitals. During a median follow-up of 72 (55-125) months, 184/193 patients (95%) could be reached. Causes of death during the follow-up were sudden (6 vs 14), non-sudden cardiac (8 vs 9), non cardiac (5 vs 9) and unknown (7 vs 6) in patients initially treated with amiodarone versus the control group respectively. The probability of death after 84 months was 30% in the amiodarone group and 45% in the control group, and was significantly lower in amiodarone treated patients with respect to all deaths (p = 0.024) as well as cardiac deaths (p = 0.027). This mortality reduction was only due to amiodarone treatment during the first year after the index infarction, whereas the survival curves did not differ significantly during the late follow-up. Thus, the risk of cardiac death is low after the first year after myocardial infarction and may not justify continued antiarrhythmic therapy in patients with initially complex asymptomatic ventricular arrhythmias. PMID- 8475361 TI - [Prenatal diagnosis of arrhythmias and associated congenital cardiac abnormalities using ultrasonography]. AB - Cardiac arrhythmias are one of the most frequent indications for a 2D and Doppler fetal echocardiographic assessment (DE). If accompanied by a non-immune fetal hydrops, arrhythmias (A) involve an increased risk of intrauterine death. Some A and mainly the bradyarrhythmias (BA) can be the first sign of major cardiac malformation (CM). In a series of 404 pregnancies between week 17 and 40 of gestation (mean 27.6 weeks), a Doppler echocardiography was carried out; in 137 (35%) fetuses (F) this examination was based on the indication of arrhythmia. 33 (24.2%) of these fetuses showed a cardiac malformation. Bradyarrhythmias were found in 20 F; 5 had a complete AV-block including, 4 with an important cardiac abnormality (TU, complete AV-canal, corr. TGV). SVT's and auricular flutters (AF) made transplacental treatment necessary in 4 fetuses (1 AF, 3 SVT); they had no major cardiac malformation. PAC's were present in 59 pregnancies of which several had minor or major anomalies. Doppler echocardiography served to define the arrhythmia and the structural cardiac malformation, but also to follow transplacental treatment. These investigations have allowed us to schedule delivery under neonatal surveillance. After birth, 5 neonates had to be treated for persistent dysrhythmia (5 SVT, 2 complete AB-blocks), and 10 for a major cardiac malformation. PMID- 8475362 TI - [Acetylsalicylic acid-induced generalized pustulosis]. AB - We report the case of a 55-year-old patient with recurrent episodes of generalized pustulosis and febrile temperatures. Histological examination revealed subcorneal and spongiform pustules. After a 4 years' course acute exanthematous generalized pustulosis, induced by acetylsalicylic acid was diagnosed. Clinical features, differential diagnosis and causative agents of this rare drug reaction are discussed. PMID- 8475363 TI - [Oxygen therapy and prematurity: lessons from the past]. AB - The history of oxygen therapy in the newborn clearly demonstrates the importance of the methodology used in clinical research. It has revealed the tragic mistakes which haunt every clinician confronted with pathology of unknown etiology. It has allowed us to determine the relative strength of the methods used in the search for various etiologies: passive or active observation, retrospective or prospective study and prospective randomized controlled trial. In addition, history has illustrated the danger of utilization of statistical tests in the absence of controlled interventions. The aim of this paper is to familiarize the practising physician with the basic concepts of epidemiology. This should allow him to be a better judge of the quality of recommendations made by "authorities". In the future, clinical epidemiology should be an essential part of medical training. PMID- 8475364 TI - [Concerning:"Moderate Paget's disease treated with pamidronate (ADP): experience in 43 patients with a single 60 mg perfusion of various duration of 1-to-24 hours" by D. Thiebaud at al. (Schweiz. med. Wschr. 1992; 122:1889-1894)]. PMID- 8475365 TI - Determination of chromium in blood and serum: evaluation of quality control procedures and estimation of reference values in Danish subjects. AB - This paper describes analytical methods to estimate environmental and occupational exposure levels of chromium in blood and serum by Zeeman atomic absorption spectrometry. Also reported is an internal quality control procedure involving a combination of an online quality control and subsequent statistical evaluation of the quality control results to evaluate the performance of the analytical methods. The solubilization of the blood by the proteinase Subtilisin A resulted in a recovery of chromium of 106 +/- 4.5%; the uncertainty was approximately 10% at a chromium level of 1 microgram l-1. The detection limit (LOD) for chromium in serum was 0.17 micrograms l-1 and 0.20 micrograms l-1 for chromium in blood. The LODs were sufficiently low for the determination of chromium in a large fraction of reference populations not occupationally exposed. The present study indicates that reference values for chromium in blood and serum are low but within the range in recent investigations, i.e. 0.04-0.35 micrograms l-1 in serum and 0.12-0.34 micrograms l-1 in human whole blood. The fraction of reference values below LOD was between 0.45 and 0.57 for chromium in serum and blood. Consequently, the reference populations were described by distribution free one-sided tolerance intervals and the precision of the estimation of the tolerance intervals was expressed as coverage intervals. The 95% one-sided tolerance limit calculated for chromium in serum was 0.60 micrograms l-1 with the coverage interval (95 +/- 4.8) percent at a probability of 0.95. Thus, the probability was 0.975 that the tolerance interval covers at least 90.2% of the distribution. In addition, the probability was 0.025 that the tolerance interval covers more than 99.8% of the population. It was only possible to calculate the 90% tolerance interval for chromium in blood with the coverage interval at 0.90 probability. The one-sided tolerance interval for chromium in blood was 0.37 micrograms l-1 with the coverage interval (90 +/- 9.9) percent at a probability of 0.90. PMID- 8475366 TI - Dietary intake of copper, chromium and zinc in Tarragona Province, Spain. AB - The dietary intake of copper, chromium, and zinc from foods in Tarragona Province (NE Spain) was determined by means of two different methods: the total diet study and the duplicate diet study. In the total diet study, a total of 375 food samples were analyzed, whereas duplicates of food consumed weekly by 20 families were analyzed for copper, chromium and zinc concentrations. Pulses were the group with the highest levels of the three elements; vegetables and fruits which are basic items in the 'Mediterranean diet', contained low concentrations of these metals. Total intakes of copper, chromium and zinc were 1156.3, 124.6 and 7522.9 micrograms day-1, respectively. On the other hand, the total intake of the elements obtained through the duplicate diet study was 1119.8 micrograms day-1 for copper, 129.0 micrograms day-1 for chromium, and 6800.1 micrograms day-1 for zinc. The daily intake of copper and zinc by the population of Tarragona Province is lower than the usually recommended values, while the intake of chromium is closer to those values. PMID- 8475367 TI - Leaded windows as a source of lead within homes. AB - Corrosion of 'cames', i.e., the lead binding or decorative strips in leaded windows, is a significant, but previously unreported source of lead within older homes. Surfaces close to the leaded windows are highly contaminated with lead but the content of lead in dust diminishes rapidly within the first 2 m away from the window and is minimal after 3 m. The dust near the window was identified, using X ray diffraction, as mainly composed of basic lead carbonate. Condensation water on leaded windows contains appreciable lead whereas for unleaded windows it is negligible. The exterior surface of unleaded windows contains more lead than the interior surface but the converse is true for leaded windows. A laboratory simulation suggested that corrosion by window condensate was likely to be the principal mechanism by which lead entered the home environment. PMID- 8475368 TI - Contributions of risk factors to elevated blood and dentine lead levels in preschool children. PMID- 8475369 TI - Analysis of chlorophenoxy acids and other acidic contaminants in food crops. AB - Several chlorophenoxy acids and chlorinated phenols were determined by means of gas chromatography in contaminated samples of cereals. Extraction of plant matrix with acetone/water mixture followed by alkaline hydrolysis was proved to be suitable for isolation of both free and conjugated residues. The use of pentafluorobenzyl bromide for volatilization of analytes, despite of enhanced ECD response, cannot be recommended for routine analysis. Methylation with either methanol/sulphuric acid or methanol/BF3 reagent can substitute diazomethane-based esterification procedure. Mass fragmentography provided the highest selectivity of detection, moreover good sensitivity--5 ppb--was achieved in this way. Even methyl derivatives of monochlorinated analytes could be, contrary to GC/ECD analysis, quantitated at this level. PMID- 8475370 TI - Pesticide residues in food in Switzerland. AB - Every year, official Swiss laboratories are involved in the analysis of about 8000 food commodities in the context of pesticide residue surveys. Between 90 to 100 different active ingredients are found normally in total foodstuffs analysed and more than 6% of the investigated samples have a contamination level exceeding the federal tolerance limits. No real improvement in what concerns the quality of food with respect to pesticide contamination has been observed these last years. PMID- 8475371 TI - Study of multi-residue methods for the determination of selected pesticides in groundwater. AB - A study of different multi-residue methods for the determination of pesticides in groundwater samples was made by comparing several extraction procedures which included liquid-liquid partitioning and solid-phase extraction. The effect of extraction conditions, such as organic solvent, volume ratio, addition of NaCl and pH, were studied. Recoveries, detection and determination limits, as well as precision of the procedures for several replicates were obtained. The pesticides studied were selected taking into account their application on citrus groves in the Plana of Castellon (Spain). These compounds included organochlorine pesticides (lindane, dicofol, chlorfenson and tetradifon), organophosphorous (dimethoate, fenitrothion and methidathion) and phenoxyacid herbicides (MCPA and 2,4-D). Analysis were carried out by high resolution gas chromatography using a dual detection system (ECD and NPD), as well as by high performance liquid chromatography (HPLC) with UV detection. This procedure was applied to several groundwater samples from Castellon province (Spain). PMID- 8475372 TI - Determination of phenoxyacid herbicides in drinking water at the ppt-level by liquid chromatography and on-line selective preconcentration. AB - On-line precolumn sample handling using an anion-exchanger is applied to preconcentrate phenoxyacid herbicides in aqueous samples prior to their LC separation. Since direct percolation of large sample volumes through the ion exchanger has to be avoided owing to the high content of inorganic anions in natural waters, a two-step preconcentration is carried out: phenoxyacids are concentrated in their neutral (acidic) form by percolation of natural samples at pH 1 first through a precolumn packed with the copolymer-based PRP-1 sorbent. Then, the PRP-1 precolumn is coupled on-line with a second one packed with the anion-exchanger and 3 ml of deionised water with 35% of acetonitrile allows the phenoxyacids to be desorbed from the PRP-1 sorbent and reconcentrated on the anion-exchanger in their ionic form. The content of the anion-exchanger is analysed on-line by coupling with a C18 analytical column and elution is made with a water-acetonitrile gradient. Detection limits in drinking water from a 500 ml sample are between 15 and 35 ng/l (ppt) and identity of phenoxyacids is reinforced by the fact that analytes are preconcentrated by the anion-exchanger. This methodology can be fully automated. PMID- 8475373 TI - Mutagenic and carcinogenic pesticides used in the agricultural environment of Gaza Strip. AB - More than 100 metric tons of formulated pesticides (about 75 pesticides) are used annually in Gaza Strip. It was found that 19 of these pesticides, that have been used, are internationally suspended, cancelled and banned pesticides. About 1100 cases of cancer have been registered in Gaza Strip (1979-1983). The distribution of cancer types among those patients are lymphoma and hematological malignancy, breast, head and neck, gastrointestinal malignancy, reproductive system, urinary system, soft tissue tumors, brain tumors and others. Consequently, the introduction and heavy use of pesticides and other toxic substances in the Gaza Strip environment is suspected to correlate with the growing incidence of cancer and other abnormalities in the nation. Precise determination of the effects of chronic exposure is, therefore, urgently needed. PMID- 8475374 TI - Direct injection into the HPLC column for monitoring the behaviour of xenobiotics in biological media. II. Behaviour of cymoxanil in fungus and locust and of E destruxin in locust. AB - Multidimensional chromatographies (MDC) implying either a single column with an unique packing designed for providing several separation modes such as internal surface reversed-phase (ISRP), or C1 large pores particles, or multi-column switching technique using the previous supports as guard columns, allow fast and easy direct monitoring of pesticides into plant or animal biological media. In such a way, the comparative study of the agricultural fungicide cymoxanil in two strains of Botrytis cinerea of different sensitivities gave concordant conclusions with the previous work using radiolabelled cymoxanil and TLC. Moreover, as a comparison, a study of the metabolism of this xenobiotic was also followed in animal biological fluids likely to contain peptidases. In locust or lobster haemolymph, an unusual isomerization into a cyclic compound was thus demonstrated accompanying the classical peptidase-depending metabolism generally observed in plants. The same chromatographic approaches were tested and compared for monitoring the metabolism of the natural insecticide toxin E-destruxin in insects. A detoxication process leading to the less toxic E-diol destruxin was evidenced in the organs or haemolymph of the locust Locusta migratoria chosen as a model of non-target insects. PMID- 8475375 TI - The use of biological methods for pesticide monitoring. AB - Since it has been recognized that analytical surveillance of surface waters for pesticides is very expensive, time consuming and does not allow a complete characterization of all parent compounds and their metabolites, it is proposed to employ aquatic organisms for screening water samples on the basis of their toxicity. Toxic effects on target organisms should indicate the occurrence of specific classes of pesticides, in this way helping the analyst in the choice of analytical procedures. This approach was tentatively applied to river Po waters (Italy) in order to evaluate the contribution of different classes of pesticides to global river pollution. PMID- 8475376 TI - Optimization of a monoclonal antibody-based enzyme immunoassay for the detection of terbuthylazine. AB - The application of immunoassays in pesticide residue analysis is of increasing interest due to the sensitivity, simple handling and fast throughput of samples. For a wide application of these assays, a sufficient supply of standardized antibodies over a long period of time is necessary. The monoclonal antibody technology is solving this problem with an increasing number of cell lines which produce antibodies against different pesticides. Hybridomas were produced by cell fusion of spleen cells from mice immunized with dichloroatrazine conjugated to bovine serum albumin and mouse myeloma cells (PAI-B3 Ag8I). After screening with a competitive enzyme immunoassay, a monoclonal antibody that was specific for terbuthylazine and was produced by a permanent hybridoma cell line was selected for immunoassay development and optimization. For this purpose, an antigen- and antibody-immobilized ELISA technique was improved by varying the test parameters. Comparing both methods, the latter turned out to be superior (50% binding = 0.8 microgram/l, detection limit = 0.14 microgram/l). PMID- 8475377 TI - DNA fingerprinting report. PMID- 8475378 TI - DNA fingerprinting report. PMID- 8475379 TI - Drug companies join forces in search for AIDS therapy. PMID- 8475380 TI - NIH budget. A new kind of earmarking. PMID- 8475381 TI - PCR enzyme patent challenged. PMID- 8475382 TI - Secrets of secretion revealed. PMID- 8475383 TI - Molecular basis for specific recognition of both RNA and DNA by a zinc finger protein. AB - Transcription factor IIIA (TFIIIA) from Xenopus oocytes binds both the internal control region of the 5S ribosomal RNA genes and the 5S RNA transcript itself. The nucleic acid binding domain of TFIIIA contains nine tandemly repeated zinc finger motifs. A series of precisely truncated forms of this protein have been constructed and assayed for 5S RNA and DNA binding. Different sets of zinc fingers were found to be responsible for high affinity interactions with RNA and with DNA. These results explain how a single protein can exhibit equal affinities for these two very different nucleic acids. PMID- 8475384 TI - Knotting of a DNA chain during ring closure. AB - The formation of knotted species on random ring closure of two DNAs that are 5.6 kilobase pairs (kbp) and 8.6 kbp in length was measured, and these data were used to calculate the effective DNA helix diameter as a function of sodium ion and magnesium ion concentration. In the presence of more than 50 mM magnesium ion, interactions between DNA segments appear to be attractive rather than repulsive. The free energy of formation of relaxed trefoil and figure-eight DNA knots and of supercoiled trefoil DNA knots was also evaluated. PMID- 8475385 TI - Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta. AB - Transforming growth factor-beta (TGF-beta) is a naturally occurring growth inhibitory polypeptide that arrests the cell cycle in middle to late G1 phase. Cells treated with TGF-beta contained normal amounts of cyclin E and cyclin dependent protein kinase 2 (Cdk2) but failed to stably assemble cyclin E-Cdk2 complexes or accumulate cyclin E-associated kinase activity. Moreover, G1 phase extracts from TGF-beta-treated cells did not support activation of endogenous cyclin-dependent protein kinases by exogenous cyclins. These effects of TGF-beta, which correlated with the inhibition of retinoblastoma protein phosphorylation, suggest that mammalian G1 cyclin-dependent kinases, like their counterparts in yeast, are targets for negative regulators of the cell cycle. PMID- 8475386 TI - Regulation of TCR signaling by CD45 lacking transmembrane and extracellular domains. AB - The CD45 protein is a transmembrane tyrosine phosphatase that is required for normal T cell receptor (TCR)-mediated signaling. A chimeric complementary DNA encoding the intracellular enzymatically active portion of murine CD45 preceded by a short amino-terminal sequence from p60c-src was transfected into CD45- T cells. Expression of this chimeric protein corrected most of the TCR signaling abnormalities observed in the absence of CD45, including TCR-mediated enhancement of tyrosine kinase activity and Ca2+ flux. Thus, the enzymatically active intracellular portion of CD45 is sufficient to allow TCR transmembrane signaling. PMID- 8475387 TI - Rescue of signaling by a chimeric protein containing the cytoplasmic domain of CD45. AB - Surface expression of the CD45 tyrosine phosphatase is essential for the T cell antigen receptor (TCR) to couple optimally with its second messenger pathways. CD45 may be required to dephosphorylate a TCR-activated protein tyrosine kinase, which then transduces an activation signal from the TCR. A chimeric molecule that contained extracellular and transmembrane sequences from an allele of a major histocompatibility class I molecule and cytoplasmic sequences of CD45 restored TCR signaling in a CD45-deficient mutant T cell line. Thus, expression of the complex extracellular domain of CD45 is not required for the TCR to couple to its signaling machinery. PMID- 8475388 TI - [Structure, physiology and physiopathology of the ureter]. AB - The function of the ureter is to transport urine from the renal pelvis toward the bladder and to protect the renal parenchyma from distally generated backflow and back pressure. The ureter manifests peristaltic activity and can adapt its mechanical characteristics to diuresis amount. The changes in ureteral function resulting from obstruction are dependent on the degree and duration of obstruction. Even the rate of urine flow, the mechanical and anatomic properties of the ureter, the nature of disease process and the age of the patient influence the response of the ureter to obstruction. It is the purpose of this report to correlate the anatomic and physiologic properties of the ureter with normal and pathologic clinical situations. PMID- 8475389 TI - [Ureteral malformations in the adult]. AB - Ureteral malformations that concern adults are very few. The aim of this review is to value the real clinical incidence and to illustrate etiology, diagnosis and therapeutical management advised in the literature. PMID- 8475390 TI - [Ureteritis]. AB - We relate our experience about ureteritis, especially non specific ureteritis. The traumatic, radiation ureteritis will be discussed in others chapters. Most cases of ureteritis are infective, and may be due to any of the organism normally found in urinary tract infections, particularly Escherichia Coli, staphylococci, streptococci, enterococci, proteus and pyocyaneus. It is really primary, but it usually ascending from an associated cystitis, descending from pyelonephritis, or due to direct spread from and adjacent inflammatory lesion such as appendicitis or salpingitis. The infection may also reach the ureter by lymphatic spread, particularly from the prostate and seminal vesicles. Any associated abnormalities of the ureter, such as stricture, megaloureter, ureterocele, and so on, will naturally predispose to infective ureteritis. As ureteritis is rarely primary, the first step in treatment must be toward the elucidation and cure of any underlying lesion. Thus calculi, cystitis, pyelitis, and so on, will need appropriate therapy, and this in itself will considerably improve or cure the ureteritis, and specially in the more acute cases. In the chronic cases with stricture formation, dilation or even excision of the stenosed portion may be required. For the treatment of the strictures we want emphasize the role of the ureteral stenting thinking its use is necessary to preserve the renal function. PMID- 8475391 TI - [Primary ureteral neoplasia]. AB - From 1983 to 1992, 29 patients with primitive ureteral tumors have been recovered in our department. All the tumors were urothelial. Urography, spontaneous and selective urinary cytology, retrograde ureteropyelography permitted a correct diagnosis in 86% of them. Ureteroscopy is not performed routinely but only when conventional radiology is doubtful or a conservative treatment can be proposed. Controlled trials on endoscopic therapy of ureteral tumours are very few and even if our results are encouraging we believe that this therapeutic option is effective and safe only in selected case and nephroureterectomy is the treatment of choice. PMID- 8475392 TI - [Controversies on the subject of traumatic lesions of the ureter]. AB - The injuries to the ureter, whether from external trauma or iatrogenic, are rare. Some problems are common to this type of pathology, independently from the causes of injuries. It is necessary a prompt diagnosis of the lesion to avoid the urinar leakage, the infection and the fibrosis of the ureteral's stumps. If the diagnosis is not prompt, the clinical pattern may be silent for some days; after, many complications will arise up: sepsis, urinomas and fistulas. When the lesion is incomplete, and there is no devascularization, the urine drainage alone, positioned above the level of the lesion, is indicated for spontaneous repairing. When the ureteral tissue loss is extensive, it is not enough a simple anastomosis between the ureteral's stumps; in these cases is necessary a more complex repair surgery or ureteral substitution. PMID- 8475393 TI - [Ureteral complications in the treatment of gynecologic diseases]. AB - Ureteral injuries are an uncommon complication after gynecological procedures. The Authors consider separately direct lesions during surgery and those following radiotherapy. For both these situations preventive criteria, which permit a lower incidence in ureteral injuries, are considered. Early diagnosis and intraoperative repair are the most important tool for surgical lesions while the exact stage of neoplasm and N.E.D. status are fundamental for lesions resulting from radiation therapy. In our opinion, best treatment of stable lesions is surgery, while endourology is not usually a definitive treatment and has only a temporary and palliative role. PMID- 8475394 TI - [The ureter in urinary diversion]. AB - Ureteral pathology is reviewed in 297 urinary diversions, which were performed consecutively in our Department, in the last 9 years. Either cutaneous or intestinal anastomosis stricture was the most common complication. Our attempts to cure definitely this problem by endourological techniques were unsatisfactory. So the Authors conclude that surgery is usually the best option. PMID- 8475395 TI - [Controversies concerning the treatment of ureteral complications following kidney transplantation]. AB - The ureteral complications after renal transplantation are urine leakage, stenosis and vesicoureteral reflux. The treatment is influenced by immunosuppression and difficult surgery (for bleeding and fibrosis). We report 8 cases with ureteral complication after renal transplantation. Stenosis were present in 5 cases: we performed ureterocystoneostomy by Politano-Leadbetter technique in 4 and pyelocystoanastomosis in 1. Vesicoureteral reflux were present in 3 cases: we preformed ureterocystoneostomy by Politano-Leadbetter technique in 2 and endoscopic infiltration with teflon of ureterovesical junction in 1. At present all patients have a normal renal function and absence of urinary tract infection. PMID- 8475396 TI - [Idiopathic retroperitoneal fibrosis]. AB - Idiopathic retroperitoneal fibrosis is generally held to be uncommon. Its etiology is unknown. The disease continues to present with early bilateral ureteric involvement. Nowadays imaging techniques permit so a timely diagnosis to preserve and reduce renal damage. The optimum method of management is still controversial. Controversies on pharmacological, endourological and surgical treatment are debated. The advantages of various types of surgery are reviewed. In the urological department of the Civic Hospital in Brescia from February 1984 to June 1992, 87 patients (6 females and 2 males) with IRP were observed. Surgical treatment was combined with corticosteroids in 6 patients. Ureterolysis was performed with omental wrapping in 5 patients, with ureteric intraperitonealisation in 2 other ones. In the last case an ileal loop replacement was performed. In 5 out of 8 patients the ureteral stricture was resected and a termino-terminal anastomosis was necessary. Long-term follow-up is satisfactory. The authors conclude that omental wrapping is the safest method of choice. PMID- 8475397 TI - [The value of sonography in ruptures of the rotator cuff]. AB - In 375 patients ultrasonography of the rotator cuff was carried out before operation. All the patients underwent acromioplasty, either alone or with additional repair of a full-thickness tear. The ultrasound findings were then compared with the intraoperative findings. Two hundred and seventy-two tears of the rotator cuff were seen on ultrasonography, and in 262 cases this was confirmed at operation. In 103 patients no rupture was diagnosed by ultrasound, but in 26 of these cases a full-thickness tear was detected on operation. These figures yield sensitivity of 91%, specificity of 89% and accuracy of 90%; the positive predictive value was 96%, the negative predictive value 75%. In most cases of incorrect evaluation the size of the tears was underestimated by ultrasonography. PMID- 8475398 TI - [Nuclear magnetic tomography in shoulder dislocation]. AB - Sixty-two patients with anterior shoulder dislocations were examined by magnetic resonance imaging (MRI). After a primary dislocation, 30 patients showed 23 (77%) tears of the glenoid labrum, 13 (45%) anterior-inferior separation of the capsula, 24 (83%) Hill-Sachs lesions, 6 fractures of the greater tuberosity and 4 glenoid rim fractures. Thirty-two patients with recurrent shoulder dislocation had 14 (44%) tears and 15 (47%) defects of the glenoid labrum, 16 (50%) anterior inferior separation of the capsula, 28 (88%) Hill-Sachs lesions and 3 glenoid rim fractures. MRI permits complete non-invasive documentation of glenohumeral instability if joint effusion is present. In the absence of joint effusion, diagnostic accuracy can be improved by application of a contrast medium. PMID- 8475399 TI - [Passive stabilizers of the glenohumeral joint. A biomechanical study]. AB - Passive glenohumeral joint stability was tested in ten cadaveric shoulder specimens, before and after venting of the intra-articular space. Force displacement diagrams were measured with anterior, posterior and inferior excursion, in the neutral position, in 90 degrees of abduction and in a combination of 90 degrees of abduction and 90 degrees of external rotation. Displacement at 50 N prior to venting averaged 11.17 +/- 6.48 mm posteriorly, 7.15 +/- 5.51 mm anteriorly and 3.41 +/- 3.73 mm inferiorly. Venting of the joint increased displacement by 47% anteriorly, 49% posteriorly and 61% inferiorly. In addition, mathematical model calculation was used to estimate the destabilizing force present at the glenohumeral joint capsule during physiological arm motion. This force approximated 970 N, clearly more than passive stabilizers alone can provide. It is therefore assumed that in addition to passive glenohumeral joint stabilization, significant active forces are effective during arm motion. PMID- 8475400 TI - [Blood supply to the cervical spinal cord and possible therapeutic consequences in cervical spinal cord injuries]. AB - The study was designed to demonstrate the blood supply to the cervical cord through radicular branches and was carried out in 23 human cadavers into which preparations were injected by the intra-articular route. One corrosion cast of the head and neck showed extravertebral anastomotic pathways. After removal of the vertebral bodies and discs from C1 to D3, the anterior spinal artery and radicular branches were identified and dissected back to their origins from the vertebral, deep or ascending cervical arteries. Twelve preparations had only one or two radicular branches reaching the cervical spinal cord. If there is traumatic compression of an ascending branch a high risk of ischaemic damage to cranial areas of the spinal cord arises. The blood supply to the cervical enlargement of the spinal cord was provided by branches of the deep cervical artery in eight preparations, but only in one by branches of the vertebral artery. We therefore plead for decompression of the anterior spinal artery and the spinal cord and for sufficient arterial blood pressure, and give our reason for these demands. PMID- 8475401 TI - [The course of intracranial pressure during respirator weaning after severe craniocerebral trauma]. AB - To analyze the characteristics of hemodynamic parameters and cerebral dynamics, the courses of intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP) and PaCO2 were analyzed retrospectively in 29 patients with severe head injury, comparing periods before and after the ventilatory mode was changed from controlled mechanical ventilation to spontaneous breathing with continuous positive airway pressure. Measurements were done before and after changing of the ventilation. Patients were allocated either to group I (n = 22, ICP remained stable: 18 +/- 2 mm Hg in both periods of observation) or group II (n = 7, ICP increased from 25 +/- 3 mm Hg to 33 +/- 4 mm Hg, P < 0.05). While changes of MAP did not reach significant levels in either group, concomitant changes in CCP appeared in group II (67 +/- 2 mm Hg to 60 +/- 2 mm Hg). Based on the observation of relatively high incidence of ICP increases and deterioration of CPP during weaning from ventilator, it is recommended that continuous ICP monitoring should be continued. PMID- 8475402 TI - [Repeated routine determination of pulmonary microvascular permeability after polytrauma]. AB - We present a technique to measure pulmonary microvascular permeability for albumin in patients with multiple trauma by means of bronchoalveolar lavage (BAL). Routine laboratory tests for the analysis of BAL fluids are used. The results were clinically validated in 10 healthy volunteers and 12 patients with multiple trauma in a first prospective study. Additionally, another 11 severely traumatized and 24 less traumatized patients were evaluated in a second prospective study. Normal values (> 0.09 +/- 0.02), posttraumatic physiological ranges (< 0.35), and a "high risk" range (> 0.5) for pulmonary microvascular permeability for albumin were developed. There was a high correlation between the first posttraumatic values of pulmonary microvascular permeability and the required duration of intensive care treatment (r = 0.81), the duration of continuous mandatory ventilation (r = 0.78) and the mean lung injury score by Murray (r = 0.76). We conclude that the presented method is harmless and useful to describe the post-traumatic course of pulmonary microvascular permeability. PMID- 8475403 TI - [Rupture of the anterior cruciate ligament. Current status of treatment]. AB - This article summarizes the present knowledge on the diagnosis of and treatment rationales for ruptures of the anterior cruciate ligament (ACL) of the knee. There is an increasing incidence of this injury due to the high number of persons involved in dynamic sports. The most significant diagnostic criterion is a positive pivot shift associated with a pathological anterior translation of the tibia in slight flexion of the knee. Instrumented testing of the knee is becoming increasing important and is standard in follow-up studies. A survey of the literature at present delineates very clearly the importance of an intact ACL for homeostasis of the knee. Loss of this structure leads to a high incidence of secondary meniscus tears with consecutive osteoarthritis of the knee. All valid studies also indicate an involuntary decrease of activity in the patients after loss of the ACL. Risk factors for early decompensation of the knee are a young age, high activity level, rupture of the collateral ligaments, congenital laxity, varus morphotype and high initial laxity. Primary repair of the ACL is possible, but results in stable ligament healing in only a limited percentage of cases. Reconstruction of the ACL with a free patellar tendon graft has become the standard procedure for many surgeons. ACL reconstruction can be performed either arthroscopically or through a "miniarthrotomy" with comparable results. Augmented repair or reconstruction using autologous flexor tendons is an alternative in certain cases. Augmentation with allogeneic material and the use of tendon allografts are still experimental and should be restricted to centers that can perform strict follow-up studies. The rehabilitation program after implantation of a patellar tendon graft can be accelerated markedly without endangering joint stability. Crutches are necessary only for the first 2-3 weeks. The success rate in terms of objective stability with an autologous patellar tendon graft is high, although specific disadvantages such as chronic patellar pain and a risk for loss of motion must be considered. PMID- 8475404 TI - [Pediatric femoral shaft fracture in the 6-14 year age group. A retrospective therapy comparison between conservative treatment, plate osteosynthesis and external stabilization]. AB - The optimal choice between operative and conservative therapy in the treatment of femur shaft fractures in school age children remains controversial. Between 1985 and 1991, 34 children aged 6-14 years were treated in our institution for fractures of the femoral shaft: 8 were treated conservatively with traction, while 10 underwent plate fixation and 15 external fixation. The 34 cases were analyzed retrospectively. In the conservatively treated group a plate osteosynthesis become necessary in 2 patients because of delayed union and fracture malalignment. Hospitalization was the longest in these children, although their concomitant injuries were the least extensive. In the group with plating there were no serious complications but open surgery is needed for two major operations for insertion and removal. The average time on crutches after plate fixation was 56 days. In the group treated by external fixation four secondary plate osteosyntheses were performed, two at an early stage because of unacceptable fracture malalignment and two others because of fracture instability after removal of the fixateur. The stay in hospital was the shortest in this group. The 11 children who had been completely managed by external fixation achieved walking without crutches in the shortest time, viz. 15 days after the operation on average. The average time to removal of the fixateur was 67 days. Review was possible in 27 of the 28 children who had been completely managed by the initial treatment method. All had unlimited hip and knee motion. Two children in the conservative treatment group were seen on radiographical examination to have a varus angulation of more than 10 degrees. In the plate and fixator group no malalignment was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475405 TI - Targeted drug delivery. PMID- 8475406 TI - Clinical pharmacokinetics and pharmacodynamics of anticancer drugs in children. AB - Pharmacokinetic variability in children with cancer is substantial and confounds drawing conclusions regarding optimal therapy based only on dose-response relationships. Careful pharmacokinetic studies performed during drug development in conjunction with an assessment of patient characteristics, such as age, renal and hepatic function, and concomitant therapy, is essential for defining those factors that may alter drug disposition. By integrating pharmacokinetic studies with measures of efficacy and toxicity, a pharmacodynamic framework can be established for guiding therapy to minimize differences in systemic exposure among subpopulations of patients (eg, impaired renal function and neonates). In selected instances when pharmacokinetic variability cannot be predicted by patient covariates, the potential for individualizing dosages based on patient specific pharmacokinetic parameters is now a clinically feasible option. The need for and benefits of incorporating such strategies into routine therapy represents an exciting area for further clinical research. PMID- 8475407 TI - Regional chemotherapy. PMID- 8475408 TI - Individualizing dosing of cancer chemotherapy. PMID- 8475409 TI - Cancer pharmacology in the elderly. PMID- 8475410 TI - Cellular pharmacodynamics of anticancer drugs. PMID- 8475411 TI - Drug resistance modulation in the laboratory and the clinic. PMID- 8475412 TI - Interactions of chemotherapy and radiation. PMID- 8475413 TI - Chemotherapy drug interactions with biological agents. PMID- 8475414 TI - New horizons in our understanding of the spinal physiology and pharmacology of pain processing. AB - Advances in the management of pain are predicated on the development of our understanding of the underlying systems. This report briefly reviews the peripheral and central substrates that define several mechanisms whereby peripheral mechanical, thermal, and chemical stimuli are encoded. Of particular interest is the growing appreciation of the changes in spinal function that occur with peripheral nerve injury and with repetitive small afferent input. These changes may serve to provide insight into a variety of pain states that are refractory to conventional management approaches. PMID- 8475415 TI - Interpretation of research results. PMID- 8475416 TI - Interpoint squared distance as a measure of spatial clustering. AB - The expectation and variance for the mean interpoint squared distance are presented. In order to evaluate these expressions it is necessary to calculate the moments of a bivariate uniform distribution defined over an arbitrary polygon. Expressions for these moments are presented, allowing the mean interpoint squared distance to be used as a measure of spatial clustering. The distribution and power of this test statistic is explored on the unit square, and the spatial distribution of 11 cases of non-Hodgkin's lymphoma is investigated to illustrate an application of the approach. PMID- 8475417 TI - Reporting by parents of longstanding illness in their adolescent children. AB - Parents' proxy reports of longstanding illness in their 15 year children are compared with the young people's own reports, both overall and between different reporting contexts; mother alone, father alone and both parents together. Parents over-report longstanding, but not limiting longstanding, illness in comparison to self report. There is no evidence of differential over-reporting by reporting context, but a number of differences are found in the likelihood of disagreement between these reporting contexts. The gender of the young person influences the relationship between proxy and self reports. PMID- 8475418 TI - Enhancing appropriate drug use: the contribution of herbal medicine promotion. A case study in rural Thailand. AB - The article presents the results of an exploratory study conducted in Thailand in 1988, comparing the results of two approaches to encourage the use of herbal medicine as a safe and cheap alternative to pharmaceuticals. The study included one government programme using a clinic-oriented approach and one non governmental programme using a community-oriented approach. Drug use in response to illness episodes was surveyed among households in two villages covered by each programme and hospital out-patient prescription records were sampled. Herbal medicines were used to treat 14.8% and 14.0% of the illness-episodes in the villages taking part in the clinic-oriented programme and to treat 62.1% and 29.7% of the episodes in the villages covered by the community-oriented programme. Herbs are mostly used after a prior treatment with pharmaceuticals has failed. Only 12.4% of out-patient prescriptions from the hospital in the government programme included herbal drugs, compared to 47.3% of prescriptions from the hospital in the non-governmental programme. The results of the study suggest that a community-oriented approach can most effectively influence the pattern of drug use in self-care. Complementary to the community-oriented approach, the government should support efforts to change the prescribing attitude of physicians and include training in traditional medicine in medical curricula. PMID- 8475419 TI - Negotiating autism: relations between parents and treatment staff. AB - This study examines the relationship between parents of autistic children and the treatment centre staff at a state autistic association. There are three main points of disagreement between parents and staff including: the prospect of a cure, the nature of the child's affection, and the uniqueness of the child and how this is related to the possibility of institutionalisation. The nature of these disagreements, and the means by which they are negotiated, are examined and discussed. PMID- 8475420 TI - The impact of childhood living conditions on illness and mortality in adulthood. AB - The aim was to explore the relationships between indicators of economic and social problems in childhood on the one hand and illness and mortality in adulthood on the other. In 1968 a representative sample of the Swedish population born 1906-1951 were interviewed about their childhood living conditions, among other things. Four indicators of adverse childhood living conditions were included. Two of these reflect economic circumstances (economic hardship; a large family, defined as four or more siblings), and two reflect social conditions (broken family; conflicts in the family). In 1981, 13 years later, this sample was re-interviewed. This allows for illness in 1981 to be related to reports of childhood conditions given in 1968. A follow-up of mortality for the period 1981 1984 was also conducted. When one controls for age, sex and father's social class, those exposed to economic as well as social problems during childhood are found to have a considerably higher risk of being ill as adults. Of the four factors analysed, conflicts in the family during upbringing is that most strongly related to illness later in life, as well as with mortality. Having a broken family, and, to some extent, economic hardship during childhood, are also clearly associated with illness later in life. These results also hold true when all four factors are included simultaneously in the model, and remain relatively unchanged when controlling for mental illness in 1968.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475421 TI - Socioeconomic disadvantage and child morbidity: an Australian longitudinal study. AB - While an extensive body of literature has demonstrated an association between socioeconomic status and child mortality, there have been relatively few papers which discuss the impact of socioeconomic inequality on child morbidity. This absence of data is partly attributable to methodological problems (need for large samples, the difficulty of assessing morbidity) and partly to the absence of relevant official health statistics. This paper reports results from the Mater University of Queensland Study of Pregnancy (MUSP) and its outcomes. The sample comprises 8556 consecutive pregnancies, of which over 90% were followed up to birth. Of those mothers giving birth, approx. 70% of children were successfully given a health assessment five years after the birth (mothers report of the child's health using a set of standard indicators). The results indicate a consistent pattern with the children of the most socioeconomically disadvantaged mothers manifesting the worst health. Thus children living in socioeconomic disadvantage have a higher rate of health service utilisation, more chronic health problems and poorer dental health. The paper discusses some social policies for redressing these inequalities. PMID- 8475422 TI - Breastfeeding and weaning in a poor urban neighborhood in Cairo, Egypt: maternal beliefs and perceptions. AB - Maternal beliefs and perceptions about breastfeeding and weaning were investigated in a series of in-depth, open-ended interviews with 20 mothers of infants aged 2-12 months in a poor neighborhood of metropolitan Cairo during July September 1990. The traditional pattern of breastfeeding well into or through the second year of life is changing rapidly, although essentially all mothers still wish to breastfeed and do so at least initially. Beliefs and behaviors reported varied somewhat by rural/urban origins of the mother herself, but exhibited consensus on many issues. The ability to breastfeed successfully is perceived to be a blessing, and to require maturity, patience and a sense of responsibility. The quantity and quality of breast milk are believed to be influenced by a wide variety of factors including the childs age and individual characteristics, the psychological and physical state of the mother, and her diet. Mothers reported a number of behaviors that are perceived to influence the quality of breast milk including changes in their diet when the infant was ill and behaviors designed to optimize the humoral qualities (hot/cold, light/heavy) of the milk. Supplementation with sugar water beings very early, and gradual introduction of other foods generally is begun soon after 40 days of age. Mixed formula and breastfeeding is commonly perceived to increase the nutritional quality of the childs diet. Weaning is ideally related to developmental milestones (walking, complete dentition) but often occurs early due to a variety of factors including maternal illness, desire for another pregnancy, and perceptions that breast milk may be inadequate. Weaning is perceived to be a difficult and dangerous transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475423 TI - Property rights and payment to patients for cell lines derived from human tissues: an economic analysis. AB - The increasing potential for commercial applications in biotechnology has given rise to new legal and ethical questions with regard to ownership of human tissue. As the potential value of human cells and tissue has risen, so have donors' calls for a share in the profits. However, in a recent California ruling (John Moore vs the Regents of the University of California), the court once again held to its traditional position that individuals do not hold property rights in their own tissue and cells. We will show that, in the rare case where tissue value may be determined prospectively, a one-time payment (and, hence granting a property right) is efficient. Moore is such a case. In general, however, the transactions costs of granting full property rights to donors of tissue and cells outweigh the benefits of such a change in policy. PMID- 8475424 TI - Social inequality in health--the role of the healthy worker effect. AB - Current occupational status is frequently used as an indicator of position in the socioeconomic structure in analyses of health inequalities. People outside the work-force are thereby ignored. One may hypothesize that due to a 'healthy worker effect' economically active people are a positively selected health group and that health-related exits from the labour marked are concentrated among low socioeconomic groups. One may therefore expect that this system of classification will show artificially small differences in health between socioeconomic groups. Analyses of material from a nation-wide representative survey and a complete set of mortality statistics confirm these expectations. When previously employed are included among currently employed, the differentials in health between the extreme groups in the occupational hierarchy widen. The system of classification has only a moderate impact on the main conclusion regarding men. For women, however, the conclusion depends more heavily on how they are classified. If one relies only on current occupation, small or inconsistent patterns emerge. Inclusion of previously employed has the effect of showing that low status women suffer from poorer health than high status women. This applies to several measures of health, i.e. morbidity, restricted activity and mortality. PMID- 8475425 TI - Construction of a socio-economic index to facilitate analysis of health data in developing countries. AB - In order to plan, implement and monitor health interventions for the most deprived sector of the population, it is necessary to identify socioeconomic groups at risk. Multiple Correspondence Analysis was used to construct a socio economic index based on data collected from a sample of 2698 households in South West district of the Ugandan Republic in 1988. This study is a part of the baseline survey done by the Government of Uganda in collaboration with UNICEF. Its aim was to reduce the incidence of death of children below 5 years from diarrhea. Two factorial axes, representing respectively the socio-cultural and the anthropological conditions, explained more than 80% of the total variability. Among the 11 variables employed the most useful in characterizing the socio economic classification were: father's occupation, parent's literacy, father's professional position and ownership of a radio. A classification in 7 levels was obtained. The first two levels are characterized as professionals and civil servants. The bottom two levels include households where both parents are illiterate and where father's primary activity is agricultural at a subsistence level. The three middle levels represent a transitional situation. In order to classify the family into the different levels, the other related variables, such as father's professional position or ownership of radio or father's religion or presence of latrine proved to be very useful. A flow chart which identifies which level a household belongs to was constructed. A general and valid observation is that families classified into the last two levels (6 and 7) constituted the population at risk for health conditions. PMID- 8475426 TI - Health effects of discontinuities in female employment and marital status. AB - The discontinuities that characterize women's work histories are also a factor in women's marital histories. Family obligations and childbearing contribute to women's unique employment histories, which include intermittent labor force participation and mobility between employers. While research has increasingly focussed on the effect of labor force participation on women's health, little attention has been given to the effect of the consistency or the stability of labor force participation on health. The purpose of this paper is to examine 15 years of employment histories and marital status changes among a cohort of women and to determine the cumulative effect of these histories on subsequent morbidity and self-reported health. The cohort of 556 women examined in this study were interviewed as part of a household interview survey completed in 1970-71, and resurveyed via a mail-out questionnaire, in 1985-86. Medical record data for the full 15 years of the study have been linked with the survey data. The findings suggest that work discontinuities and marital status discontinuities are unrelated to morbidity during the study period. However, two or more changes in marital status are related to poor self-reported health at follow-up. PMID- 8475427 TI - Medical slang and its functions. AB - Medical slang is analyzed in the developmental perspective of the physician's career. More than 300 terms gathered by ethnographic methods are classified by social categories: (1) the setting--various types of hospitals and facilities, (2) the players--care-givers and care-receivers, (3) the social processes- patient admission, diagnosis, treatment and discharge, and (4) death and dying. Slang usage generally begins during the third year of medical school when students rotate among clinical services and peaks during the internship year. Male and female clinicians are similar in slang usage. Five psychosocial functions of medical slang are discussed. PMID- 8475428 TI - Health needs, demand for health services and expenditure across social groups in Italy: an empirical investigation. AB - The shortage of empirical studies on socio-economic factors influencing demand for health care and inequalities across social groups is dramatic in the case of Italy. The present study aims at discussing these issues, although its results are to be considered mainly methodological, given the small dimension of the sample (n = 807). A survey was carried out in a 'qualitative' sample of 9 Local Health Units of different Italian regions. Attention was paid to report every 'illness episode', considered as a cause of demand for health services, within the reference period (4 weeks) in order to properly link health needs with utilization of health services and relative expenditure. The assessment of health status across social groups, using 4 different indicators, shows the weakest social groups as the most vulnerable. The same groups report higher per capita health services uses and expenditures than their morbidity conditions would require. Assuming equity to be defined as 'equal use for equal need' a particular use-need ratio is developed (i.e. health services used per illness episode) able to capture the 'intensity' of health services use and expenditure per need. The 'over-equity' towards the less favoured groups is interpreted as a possible accomplishment of the N.H.S. fundative goals. A structural model of determinants of health services utilization, carried out through the LISREL technique (R2 = 0.36), confirms the irrelevance of the social variables with respect to need variables. PMID- 8475429 TI - Deep venous thrombosis after spinal surgery. AB - Eighty-six consecutive patients undergoing spinal surgery were studied with preoperative and postoperative compression ultrasonography of the lower extremities to identify acute deep venous thrombosis. Compression stockings were the only method of prophylaxis. Postoperative deep venous thrombosis developed in five patients (6%). Serial ultrasound scanning revealed propagation of the thrombus proximal to the knee in one patient, who was the only patient to be anticoagulated. There were no statistically significant differences in the incidence of deep venous thrombosis compared to the type of procedure, age, sex, length of operation, or duration of bed rest. In conclusion, deep venous thrombosis distal to the inguinal ligament is unusual after spinal surgery. Given the potential complications of anticoagulation, we recommend only mechanical prophylaxis. PMID- 8475430 TI - Nonoperative treatment in burst fractures of the lumbar spine (L2-L5) without neurologic deficits. AB - A retrospective review of 20 patients treated nonoperatively for burst fractures of the lumbar spine (L2-L5) was performed. All patients were neurologically intact at the time of injury. Follow-up averaged 3.9 years with a range of 2.1 to 9.1 years. Fourteen patients were men and six were women. The average age at injury was 35.8 years (8-67 years). Sixty-five percent of the injuries were the result of motor vehicle accidents and 35% falls from height. Fifty-five percent were two-column injuries and 45% three-column injuries. Kyphotic deformity averaged 8 at injury (-7 to 30) and 9.6 at follow-up (-8 to 33). Computed tomography scans were performed in nine patients during evaluation of injury. Spinal canal compromise averaged 40% (18-75%). Eighteen patients (90%) were considered to have a good to excellent functional outcome, whereas two patients had a fair outcome. No patient had a poor outcome. In no patient did neurologic deterioration or symptomatic spinal stenosis develop. Twenty-five percent of patients had no back pain, 70% mild back pain, and 5% moderate back pain. No patient was totally incapacitated by pain. Of those employed, all returned to full-time work. Nonoperative treatment should be considered as an alternative in the treatment of lumbar burst fractures (L2-L5) in patients presenting without initial neurologic deficits. PMID- 8475431 TI - Optoelectronic evaluation of trunk deformity in scoliosis. AB - In this study, truncal deformity in patients with scoliosis was evaluated by circumferential scanning using an optoelectronic device (Optronic Torsograph, Anima Corp., Tokyo, Japan). This device generates cross-sectional skin surface topography at 10 axial levels to provide a three-dimensional representation of truncal shape. Ninety-three patients with suspected idiopathic scoliosis were evaluated with conventional Cobb measurements, and their parameters were computed using the device's measurements. The geometric cross-sectional indexes correlated poorly with the Cobb angle and were highly variable during repeated measurements. The optoelectronic device's angle, a measure of centroid curvature, correlated highly with the Cobb angle for primary spinal curves. The highest correlation was observed in thoracolumbar curves. This optoelectronic device has clinical relevance as a method for further scoliosis screening and monitoring the progression of spinal curvature in a patient. PMID- 8475432 TI - Spinal involvement in children and adolescents with Gaucher disease. AB - Nineteen patients with type I Gaucher disease with spinal involvement first diagnosed during childhood, were followed for 2 to 24 years (average 9 years), and their clinical and radiologic history reviewed. Patients presented with three types of pain: mild pain that was defined as nonspecific, severe pain due to bone crisis, and pain associated with vertebral collapse. Collapse of vertebra occurred gradually anywhere along the thoraco-lumbar spine, and usually more than one vertebra was involved. In three patients, rectangular collapse was noted. Six patients suffered from central vertebra collapse, and two from anterior wedge compression. Further vertebral collapse with signs of root and cord compression developed in three patients as they grew. Awareness to the possibility of progressive vertebral collapse and periodic follow-up might prevent severe complications. PMID- 8475433 TI - Progressive scoliosis with vertebral rotation after lumbar intervertebral disc herniation in a 10-year-old girl. AB - A case report of a 10-year old girl with a herniated disc is presented. The most significant symptoms were progressive scoliosis with a flat back and paravertebral muscle spasm. An absent H reflex on the left and an increased latency of the somatosensory-evoked potentials of the left posterior tibial nerve were found. The computed tomographic scan of the lumbar spine showed a large central left-sided disc protrusion at the L5-S1 level. Our case presents the youngest patient with documented intervertebral disc herniation and the only one with severe scoliosis and vertebral rotation. The curve was not structural because it improved with surgery and an orthosis was not necessary. PMID- 8475434 TI - Congenital anomaly of the second cervical vertebra predisposing to progressive cervical myelopathy. A case report. AB - The authors describe a previously unreported constellation of developmental anomalies of the C2 vertebra, which predisposed to the development of cervical myelopathy in a young patient. The embryology of the vertebral column is reviewed briefly, and the origin of each anomaly of the C2 vertebra is traced to one of the two early stages in development as follows: 1) the formation of the mesenchymal vertebra or 2) its induction to cartilage. This case emphasizes the importance of congenital stenosis in the development of cervical myelopathy in young patients. The outcome is favorable when it is treated aggressively. PMID- 8475435 TI - Mechanical process and growth cartilages. Essential factors in the progression of scoliosis. AB - This study showed that the worsening of scoliosis was the result of a mechanical phenomenon. The key feature in this mechanical process was the finding that cuneal deformation affects only part of the vertebral body. The onset of scoliotic curvature occurred as a result of intervertebral motions. However, the worsening was essentially caused by deformation of the vertebral bodies. After the onset of scoliosis, the orientations of the vertebrae were modified in all three planes, and as a result, the spine became mechanically unstable. As a result of this mechanical instability, intervertebral pressures no longer were distributed equally but were concentrated at the junction of the growth cartilages of the vertebral body, near the pedicle on the concave side. Osseous growth was perturbed in this area, the vertebra became deformed, and the vertebral body became wedge shaped. These cuneal deformations resulted in a relative change of position between adjacent vertebral bodies and led to a worsening of the scoliotic curve without involving any articular motion. This phenomenon occurred mostly in the apical region because of the geometric shape of the curvature. PMID- 8475436 TI - Neuromorphometric changes in the ventral spinal roots in a scoliotic animal. AB - The morphologic changes were investigated in the ventral and dorsal spinal nerve roots in a strain of white leghorn chickens that genetically was predisposed to have idiopathic scoliosis. In the ventral spinal roots in chickens with scoliotic curves, small myelinated fibers were increased in number and appeared in clusters. The number of small fibers did not correlate with the degree or the duration of the deformity. In 8 of the 15 chickens of the genetic scoliotic strain that did not have spinal curves, changes in the myelinated fibers, similar to those in chickens with scoliotic curves, were seen. These findings suggest that abnormalities in the myelinated fibers of the ventral spinal nerve roots may be the primary genetic lesion that, with variable penetrance, influences the development of scoliosis. PMID- 8475437 TI - The migration of a Harrington rod after cervical fusion. AB - A patient was treated for an anterior dislocation of C4 on C5 with an open reduction and Harrington rod hook fixation. The compression rod dislodged and migrated through the foramen magnum into the cerebellum 4 years later. This case represents an unusual complication of Harrington rod instrumentation in the cervical spine. PMID- 8475438 TI - The effect of multilevel laminectomy on the cervical spine of growing cats. An experimental study. AB - This experiment was undertaken to observe the effect of multilevel laminectomy on the cervical spine of growing cats. Wide cervical laminectomy was done from C3 to C6 on 24 immature cats and 24 mature cats. Cervical kyphosis gradually developed in the growing cats postoperatively after 4 months; normal cervical curves were maintained in the mature cats. Corporal subluxation at the kyphotic segment was detected postoperatively after 4 months, but the characteristic wedge-shaped deformity of the vertebral body of the swan-neck deformity was not detected using serial radiographs during the 12-month observation period. Histologically, there was no evidence of thinning or early fusion of the anterior part of the physis throughout the observation period. Post-laminectomy kyphosis developed as the result of forward subluxation of vertebral bodies because of the destabilizing surgery. PMID- 8475439 TI - The effects of quadriceps fatigue on the technique of lifting. AB - A biomechanical analysis was performed of lifting before and after fatiguing the quadriceps muscles. The hypothesis tested was that when the quadriceps muscles were fatigued the lifter would change lifting technique from more of a squat (leg) lift to more of a stoop (back) lift to decrease the demand on the quadriceps muscles. The hypothesis was broadly supported, and three variables changed significantly with fatigue: trunk angular velocity, which increased, and knee moment integral and hip angles, which both decreased. These changes are all consistent with a change from more of a squat toward a stoop technique. The fact that the technique of lifting changes with quadriceps muscle fatigue underlines the importance of the physiologic condition of these muscles and suggests that rehabilitation of low-back-injured workers should include the quadriceps muscles. The amount of work performed should be controlled to avoid the development of local muscle fatigue and subsequent changes in performance. PMID- 8475440 TI - The effect of imposed leg length difference on pelvic bone symmetry. AB - This study was designed to examine the effect of varying degrees of imposed leg length difference on symmetry of the innominate bones in healthy college women with relatively equal leg lengths. Subjects' leg length was determined by clinical and roentgenographic procedures. Position of the innominate bones with and without lifts under one foot was measured with respect to the transverse plane using the Waterloo Spatial Motion and Recording Technique (WATSMART; Northern Digital, Inc., Waterloo, Ontario, Canada), which allows very high spatial resolution. Our results show that posterior innominate bone rotation occurs on the side of the lengthened limb, and anterior rotation occurs on the shorter limb. The amount of pelvic obliquity increased in an approximately linear fashion as the leg length difference was increased from 2/8 to 7/8 inch. Some individual differences were evident. PMID- 8475441 TI - Percutaneous biopsy in the anterior thoracic spine. AB - Over a 24-month period, seven patients have undergone nine diagnostic closed percutaneous biopsies of thoracic vertebral body lesions. Seven of the nine biopsies were performed using the Craig trephine biopsy set. All seven biopsies provided diagnostic material. Two biopsies were performed with 22-gauge needles and aspiration technique. One provided diagnostic material. The only complication was a small pneumothorax that spontaneously resolved. Current editions of orthopedic texts give mixed recommendations as to the route of vertebral body biopsy in the thoracic spine. Most recommend open rather than percutaneous biopsy, particularly above T10. Review of current orthopedic literature, however, reveals overwhelming support for the use of closed biopsy techniques as the procedure of choice for tissue diagnosis of thoracic vertebral body lesions. As in this limited series, the reported positive biopsy ratio is high and the complication rate acceptably low. PMID- 8475442 TI - Magnetic resonance imaging evaluation of the spine with metal implants. General safety and superior imaging with titanium. AB - We studied the cases of 15 patients who underwent postoperative magnetic resonance imaging evaluation after being treated with metal spinal implants. Spine stabilization was required in traumatic injuries for eight patients, cancer destruction in four patients, late cervical subluxation in one patient, spondylosis in one patient, and spondylolisthesis in one patient. A variety of stainless steel and titanium spinal implants were used. The images were evaluated for spinal and implant positioning and artifact production. Both stainless steel and titanium implants were imaged safely and there was no evidence of implant migration of local tissue-heating effect. The titanium spinal implants allowed postoperative spine imaging without the significant image distortion characteristic of the stainless steel implants. The stainless steel implants created significant artifact that impaired the usefulness of the magnetic resonance imaging evaluation. PMID- 8475443 TI - Closed reduction of traumatic cervical spine dislocation using traction weights up to 140 pounds. AB - The purpose of this study was to demonstrate that Gardner-Wells skull tong traction up to 140 lb was both safe and effective in reducing dislocation, without fractures, of facet joints involving the C4-C7 vertebral bodies when applied by experienced practitioners in a spinal cord injury center under close scrutiny. Twenty-four awake patients were selected for the study (age range, 16 82 years). These patients were evaluated for the number of millimeters (7-17 mm) of dislocation as measured from the posterior aspect of the superior vertebral body to the posterior aspect of the inferior vertebral body at the level of injury. The maximum weight required to produce the reduction of the facet joints and the time from the onset of traction were recorded. The patients' neurologic status was monitored before traction, after each increment in weight applied, and after reduction. Careful examination of motor function and sensation was done and recorded at each interval. The 24 patients with cervical spine dislocation of the facet joints underwent successful reduction with traction weights (range, 10-140 lb). Seventeen patients required weights of more than 50 lb. The traction procedures lasted for a period of 8-187 minutes per procedure. Worsening neurologic status did not occur in any of the patients involved in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475444 TI - Dysphagia complications in ankylosing spinal hyperostosis and ossification of the posterior longitudinal ligament. Roentgenographic findings of the developmental process of cervical osteophytes causing dysphagia. AB - This is the first report of the process of formulation of a cervical osteophyte causing dysphagia. The patient had ankylosing spinal hyperostosis and OPLL and was followed radiographically for a long time before the onset of dysphagia. The radiological observation suggested that dysphagia was produced when the immobile part of the esophagus was compressed by the anterior projecting cervical osteophyte. The immobility of the esophagus is an important factor in determining whether dysphagia occurs. Another possible contributing factor to dysphagia in this patient was the ossification of the cervical anterior and posterior longitudinal ligaments. The OPLL affected intervertebral segmental motion and induced the formation of anterior projecting cervical osteophytes. PMID- 8475445 TI - Automated percutaneous lumbar discectomy as treatment for lumbar disc disruption. PMID- 8475446 TI - Spinal tuberculosis with translational instability. PMID- 8475447 TI - Chronic spontaneous cervical epidural hematoma. Report of a case presenting with only radicular symptoms. PMID- 8475448 TI - Bilateral traumatic L4 pedicular fractures in a healthy male athlete. A case report. PMID- 8475449 TI - Magnetic resonance demonstration of the cervical spine after anterior discectomy using acrylic cement. PMID- 8475450 TI - The effect of lower limb ischemia on somatosensory evoked potentials during spinal surgery. Report of two cases and review of the literature. PMID- 8475452 TI - Awards and recognition in science: a distortion of reality. PMID- 8475451 TI - Comments on the direction of blood flow in the central placental vessel in the rat. PMID- 8475453 TI - Blueprint for the prevention of birth defects in the year 2000. PMID- 8475454 TI - Occurrence of embryotoxicity in mouse embryos following in utero exposure to 2' deoxycoformycin (pentostatin). AB - Previous investigations had shown that i.p. injection of 2'-deoxycoformycin (dCF; pentostatin; 5 mg/kg) on either E7 or E8 into pregnant mice results in a 61-81% resorption rate at E17. The incidence of visible gross malformations among the surviving conceptuses was exceptionally low (3%) at the time of necropsy on E17 and was unrelated to dCF dose (Knudsen et al., Teratology, 40:5-626, '89; Teratology, 45:91-103, '92). These findings demonstrated the embryotoxicity of dCF but provided no clues as to the site(s) of dCF action. To define the lesion site(s), we have now examined embryos at 72 h (E10), 96 h (E11), and 120 h (E12) following administration of a highly embryotoxic dose of 5 mg dCF/kg to dams on E7. Deoxycoformycin caused multiple abnormalities and growth retardation, and the temporal sequence between maximal abnormal embryo incidence and resorption frequency was established. The quantitative data show that the maximal occurrence of abnormal embryos on E10 (71%) was followed by a maximal resorption rate on E12 (78%). There was a strong correlation (r = -0.82; P < 0.05) between the rapid decline of percent abnormal embryos over E10-E12 and the simultaneous increase in resorption rate, with linear regression analysis showing nearly equal but opposite slopes (-31.2% vs. +35.8% per gestational day, respectively). This suggests that one or more of the abnormalities seen at E10 is associated with the death and resorption of the embryo at E12. The dCF treatment perturbed a wide spectrum of developmental events, including neural tube closure, craniofacial and limb development, turning of the embryo, and growth retardation. None of the individual abnormalities, however, can quantitatively account for the high percentage of dead and resorbed embryos. Therefore, the specific cause of dCF induced embryolethality is not clear. There is evidence both for direct dCF toxicity at specific embryonic sites as well as for a generalized retardation in the rate of development. PMID- 8475455 TI - Comparative teratogenicity and metabolism of all-trans retinoic acid, all-trans retinoyl beta-glucose, and all-trans retinoyl beta-glucuronide in pregnant Sprague-Dawley rats. AB - When single large equimolar doses (0.38-0.41 mmol/kg BW) of all-trans retinoic acid (RA), all-trans retinoyl beta-glucose (RBGL), and all-trans retinoyl beta glucuronide (RBG) are administered orally in oil on day 8.5 of pregnancy to Sprague-Dawley rats, RA and RBGL proved highly teratogenic, whereas RBG was not. Indeed, fetuses from RBG-treated dams were 16% heavier (P < 0.01) than control fetuses. After dosing with RA and RBGL, RA appeared in large amounts within 0.5 h in the maternal plasma and within 1.0 h in the embryo. In contrast, orally administered RBG seemed to be absorbed much more slowly, to be converted very slowly to RA, and not to accumulate either as RBG or as RA in the embryo. When incubated in vitro with embryos and attached membranes, however, both all-trans RBG and all-trans RA were partially converted to 13-cis RA. The nonteratogenicity of RBG, in contrast to RA, seems to be due to a much slower rate of GI absorption, a slow rate of hydrolysis to RA, a limited passage from the maternal circulation into the embryo, and a lower inherent toxicity. PMID- 8475456 TI - Importance of early exposure to 13-cis retinoic acid to induce teratogenicity in the cynomolgus monkey. AB - The teratogenic potential of 13-cis retinoic acid (13-cis RA) was further assessed in cynomolgus macaques (Macaca fascicularis) following exposure to two different regimens during the preorganogenic period to determine the influence of time of treatment on the 13-cis RA malformation syndrome established previously (Hummler et al., Teratology, 42:263-272, 1990). In experiment (Exp) 1, 13-cis RA was orally administered once daily (2.5 mg/kg) on gestational day (GD) 16-25 and twice daily (2 x 2.5 mg/kg) on GD 26-27. In Exp 2, the same oral dose was administered once daily on GD 10-20 and twice daily on GD 21-24. Although the ear was affected at about the same incidence (6/9, 67%) in Exp 1 as previously reported, the defects were less severe. Except for hypoplastic vermis of the cerebellum (2/9, 22%), no other defects were seen. In Exp 2, the teratogenic effects of 13-cis RA on the craniofacial skeleton (1/9, 11%), external ear (5/9, 56%), and heart (2/9, 22%) were similar to that reported by Hummler et al.; however, no thymus or cerebellar malformations were observed. Analysis of the three different treatments (GD 16-27 in Exp 1, GD 10-24 in Exp 2, and GD 10-27 in Hummler et al.) suggests that the sensitive periods in the macaque are 1) craniofacial skeleton and heart GD 10-24, 2) thymus and cerebellum > GD 24, and 3) external ear GD 16-24, although the defects are less severe following the shorter exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475457 TI - Omphalocele and gastroschisis: a collaborative study of five Italian congenital malformation registries. AB - During 1984-1989, 116 cases of omphalocele and 42 cases of gastroschisis were detected among 736,760 consecutive births in the area covered by five Italian congenital malformation registries. The prevalence rate was 1.6 per 10,000 for omphalocele and 0.6 per 10,000 for gastroschisis. Three additional cases were detected among spontaneous abortions, giving a total of 117 cases of omphalocele and 44 of gastroschisis. No variations in prevalence rates were observed among registries. A cluster of omphalocele was found in 1989 in Firenze. All cases were sporadic except for one infant with two sibs with Beckwith-Wiedemann syndrome. A predominance of male infants was observed for both defects. This study confirms the very young maternal age for isolated gastroschisis as compared to that for omphalocele and controls. Birth weight and the percentage of small-for-date is different among isolated gastroschisis, omphalocele and controls. Associated anomalies occurred in 45 cases of omphalocele and 11 cases of gastroschisis. Our data confirm the association of omphalocele with trisomies 13 and 18. Twelve cases of omphalocele and gastroschisis with associated limb defects were classified as limb body wall complex. The possible differences in etiopathology between omphalocele and gastroschisis, both isolated and associated, are discussed. PMID- 8475458 TI - Development of in vitro fertilized mouse embryos exposed to ethanol during the preimplantation period: accelerated embryogenesis at subtoxic levels. AB - This study examined the effects of ethanol (EtOH) on mouse preimplantation development using an in vitro culture method. Embryos at the 1-cell, 2-cell, or 4 cell stage were exposed for 24 h to medium containing EtOH, then further cultured without EtOH to determine their ability to form blastocysts and to eventually hatch from the zona pellucida. EtOH exposure either arrested or enhanced normal development, depending on dose and embryonic stage of exposure. Exposure of 1 cell and 2-cell embryos to 1.6% (w/v) EtOH decreased blastocyst formation and hatching, and exposure of 1-cell embryos to 0.4% EtOH inhibited their development. At 0.1%, EtOH had an opposite effect, causing an increase in the percent blastocyst formation of treated 1-cell and 2-cell embryos. Neither inhibition nor stimulation of blastocyst formation occurred in 4-cell embryos exposed to 0.1-1.6% EtOH. Using an in vitro outgrowth model of implantation, embryos that reached the blastocyst stage were further tested for their ability to produce differentiated trophoblast cells. Blastocysts previously exposed to 0.1% EtOH during the 1-cell stage appeared to form adhesive trophoblasts earlier than control embryos, indicating that EtOH exposure can induce precocious differentiation of the trophoblast cells. The EtOH treated blastocysts contained significantly more cells than control blastocysts. These results indicate that EtOH can alter preimplantation development by either inhibiting or accelerating cell growth and differentiation. PMID- 8475459 TI - Renal dysplasia, megalocystis, and sirenomelia in four siblings. AB - First degree relatives of infants with bilateral renal agenesis or dysplasia have an increased risk of renal abnormalities including renal agenesis. We report a family in which four successive offspring exhibited a previously undescribed combination of congenital lethal renal disorders: bilateral renal dysplasia, megalocystis secondary to urethral obstruction and, sirenomelia with associated renal agenesis. PMID- 8475460 TI - Intermittent pattern of neural tube closure in two strains of mice. AB - Development of the neural tube is often described as a continuous process that begins in the cervical region of the embryo and proceeds both rostrally and caudally. Examination of neural tube closure in the cranial region of LM/Bc and SWV/Bc mice revealed an intermittent pattern with four distinct areas of closure. Closure I begins at the level of somites 1-3 and proceeds bidirectionally. Closure II is initiated at the prosencephalic-mesencephalic border and also proceeds bidirectionally. Closure III is unidirectional, beginning adjacent to the stomodeum and proceeding caudally to meet closure II. Finally, closure IV takes place over the rhombencephalon where it meets closure II to complete rostral neural tube closure. In these two strains of mice anterior neural tube closure progressed as somite number increased. However, the SWV strain required a longer gestational time to develop equal numbers of somites and therefore to complete closure. In light of the intermittent pattern of closure observed in mice, the development of the rostral nervous system in other mammals, including humans, should be reconsidered. PMID- 8475461 TI - The developmental toxicity of inhaled methanol in the CD-1 mouse, with quantitative dose-response modeling for estimation of benchmark doses. AB - The developmental toxicity of the alternative motor vehicle fuel methanol was assessed in mice by the inhalation route. Pregnant CD-1 mice were exposed to 1,000, 2,000, 5,000, 7,500, 10,000, or 15,000 ppm methanol for 7 hr/day on days 6 15 of gestation. Sham-exposed controls were exposed to filtered air under similar conditions. Additional control groups were left in their home cages either unhandled or food-deprived for 7 hr/day to match the food deprivation experienced by the exposed mice. Dams were observed twice daily and weighed on alternate days during the exposure period. Blood methanol concentrations were determined in some mice on gestation days 6, 10, and 15. On day 17, the remaining mice were weighed and killed and the gravid uteri removed. Implantation sites, live and dead fetuses and resorptions were counted, fetuses were examined externally and weighed as a litter. Half of each litter was examined for skeletal morphology and the other half of each litter was examined for internal soft tissue anomalies. One dam died in each of the 7,500, 10,000, and 15,000 ppm methanol exposure groups, but no dose-response relationship was evident for maternal death. The sham-exposed and food-deprived controls as well as all methanol exposed dams gained less weight than did unexposed dams fed ad libitum, but methanol did not exacerbate this effect. Significant increases in the incidence of exencephaly and cleft palate were observed at 5,000 ppm and above, increased embryo/fetal death at 7,500 ppm and above (including an increasing incidence of full-litter resorptions), and reduced fetal weight at 10,000 ppm and above. A dose-related increase in cervical ribs or ossification sites lateral to the seventh cervical vertebra was significant at 2,000 ppm and above. Thus, the NOAEL for the developmental toxicity in this study was 1,000 ppm. A log-logistic dose response model was applied to the incidence data for exencephaly, cleft palate, resorption and cervical rib, and maximum likelihood estimates (MLEs) and benchmark dosages (BDs, the lower 95% confidence interval of the MLEs) corresponding to 1% and 5% added risk above background were calculated. The MLE for 5% added combined risk of having either exencephaly or cleft palate or being resorbed was 3667 ppm, and the corresponding BD was 3,078 ppm. For cervical rib, the 5% added risk values for the MLE and BD were 824 and 305 ppm, respectively. The BDs for 1% added risk were 1915 ppm for exencephaly, cleft palate or resorption, and 58 ppm for cervical rib.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475462 TI - Developmental toxicity of caffeine in the larvae of Xenopus laevis. AB - To examine the developmental toxicity of caffeine, Xenopus larvae just after hatching, were continuously exposed to 100-2,000 mg/L caffeine for 48 hours. Caffeine interfered with development of Xenopus larvae at a concentration of 100 mg/L and above in a concentration-dependent manner. Characteristic external abnormalities, such as shortened body with wavy fins, were observed, the severity of which was clearly concentration dependent. These larvae were frequently accompanied by abnormal body flexure and edema in the fin. Light microscopy revealed that exposure to caffeine induced severe damage in the myotome and neural tube, and at higher concentrations, the epidermal tissue was also affected. Myoblasts showed wide intercellular spaces, and their cytoplasm lost uniform staining. Ultrastructural studies of myoblasts revealed distinct myofibril disorganization and degeneration, and mitochondrial alterations. In the neural tube, cells at the dorsal part of tube showed wide intercellular spaces and some of them were segregated to the peripheral region. Furthermore, vacuole like structures of various sizes appeared in the white matter. The outer layer of epithelial cells in the epidermis were vacuolated and swollen. With regard to the pathogenesis of myofibril damage, caffeine appeared to cause a disturbance of intracellular calcium regulation, by releasing calcium ions from the sarcoplasmic reticulum, and the mitochondrial changes observed in myotomal cells were considered to be reflective of this increased intracellular calcium ion levels. It is speculated that caffeine interferes with cell adhesion in the myotome and neural tube by affecting calcium ion regulation. PMID- 8475463 TI - Embryotoxic effects of chlorobutanol in cultured mouse embryos. AB - Chlorobutanol (CB) is a commonly used preservative which is added to numerous pharmaceutical preparations, and it is the active ingredient in certain oral sedatives and topical anesthetics. Chlorobutanol has demonstrated adverse effects in adult tissues, but CB has not been previously investigated for its effect on the developing whole embryo. The method of whole-embryo culture was used in this study to expose mouse embryos during two stages of organogenesis to CB at final concentrations of 0 (control), 10, 25, 50, 100, and 200 micrograms/ml. Embryos were evaluated for heart rate (HR), malformations, and somite number, and embryos and visceral yolk sacs (VYSs) were assayed for total protein content as a measure of overall growth. Neurulating (3-6 somite) embryos were malformed and growth retarded by exposure to CB concentrations > or = 25 micrograms/ml, with decreased VYS growth at > or = 50 micrograms/ml and decreased HR at > or = 100 micrograms/ml CB. Early limb-bud stage (20-25 somite) embryos were malformed at CB concentrations > or = 50 micrograms/ml and growth retarded at > or = 100 micrograms/ml, with decreased VYS growth at 200 micrograms/ml and decreased HR at > or = 100 micrograms/ml CB. Thus, CB produces dysmorphogenesis in mouse embryos in vitro, and neurulating embryos are somewhat less sensitive than early limb-bud stage embryos. The concentrations of CB that interfere with normal embryonic development are within the range of human blood levels measured following multiple doses of CB. Preparations containing CB should be used with caution during pregnancy, particularly when repeated dosing may allow accumulation of CB to potentially embryotoxic levels. PMID- 8475465 TI - Young maternal age and smoking during pregnancy as risk factors for gastroschisis. AB - Three maternal risk factors (maternal age, cigarette smoking, and infant's month of birth) have been reported to be associated with fetal gastroschisis. In order to study these risk factors further, a prospective population-based study was designed, using 62,103 consecutive second-trimester singleton pregnancies enrolling in a maternal serum alpha-fetoprotein screening program between January 1, 1980 and April 30, 1989. Gastroschisis occurred in 21 of those pregnancies. Pregnancies in women younger than 20 years of age were at 7.3 times greater odds for being affected with gastroschisis than pregnancies in women aged 25 or older (95% confidence interval 2.4 to 22). For pregnant women aged 20 to 24 years, the odds were 1.9 times greater (95% confidence interval 0.7 to 5.0). Pregnant women who smoked cigarettes were at 2.1 times greater odds than non-smokers (95% confidence interval 0.9 to 4.8). When these smoking data were combined with smoking data from two other published studies, the consensus odds ratio was 1.6 (95% confidence interval 1.2 to 2.2). Infant's month of birth was not associated with gastroschisis. Evidence from the present study and other published studies clearly establishes a greater risk for fetal gastroschisis in pregnant women younger than age 20, even after adjustment for smoking status. Cigarette smoking also appears to be a risk factor, when data from this and two previously published studies are combined. PMID- 8475464 TI - The role of oxygenation in embryotoxic mechanisms of three bioreducible agents. AB - Many xenobiotics used in the treatment of hypoxic pathogens and tumors require reductive bioactivation under anaerobic conditions for maximal effectiveness and/or toxicity. A number of agents of this type have been shown to be teratogenic in vitro and/or in vivo. Early conceptuses may be vulnerable to these agents because they exist in a relatively anaerobic environment and have the capacity to perform reductive metabolism. It has been hypothesized that the single electron redox potential of bioreducible agents plays a dominant role in the capacity to induce anomalies. We examined the in vitro embryotoxicity in rats of three bioreducible drugs of similar redox potential under normoxic and hypoxic conditions as well as the capacity of those drugs to redox cycle and to damage DNA in embryonic tissue. Adriamycin, mitomycin C, and niridazole were shown to have differential embryotoxic responses in vitro to altered oxygenation. Studies of the bases of drug action showed (1) Adriamycin induces DNA strand breaks at concentrations that correlate well with embryolethality; (2) Mitomycin C does not induce strand breaks, but its dysmorphogenicity is increased by hypoxia; and (3) Niridazole does not produce DNA damage but appears to induce asymmetric malformations by depleting embryonic oxygen through redox cycling. Together the studies show that dysmorphogenic and embryolethal effects may result from separate mechanisms and that oxygenation plays an important role in those mechanisms. PMID- 8475466 TI - Skeletal development following heat exposure in the rat. AB - The effects of gestation day (GD) 10 heat exposure in the rat were studied to determine the temperature-response relationship for the induction of skeletal and other defects. Conscious pregnant rats (Experiment 1) were exposed to various temperatures in a warm air chamber. Body temperature was measured using a rectal probe, and these measurements were confirmed as representing core body temperature in separate animals using telemetric procedures. Those animals whose core body temperature was raised to 41-41.9 degrees C had over 90% malformed pups (examined at postnatal day (PND) 3), and a 25% reduction in the percent of live pups per litter. Animals whose temperature was raised to 39.2-40.9 degrees C had a low incidence of pups with similar types of malformations. The primary types of malformations were of the axial skeleton, consisting of fusions and other abnormalities of the ribs and vertebral elements, and a decrease in the total number of ribs and centra. The acute maternal effects of these temperature increases were signs of heat exhaustion during and 1-2 hr after exposure, but there were no permanent changes in weight gain or other signs. When temperatures were raised to > or = 42 degrees C, all maternal animals died. In a second study (Experiment 2), pregnant rats (from a different supplier) were anesthetized to determine the effect of reducing maternal stress and were exposed to heat as in Experiment 1. Those animals whose core body temperature was raised to 42-42.5 degrees C for 5 min had pups with similar responses to those in Experiment 1 at 41-41.9 degrees C, although the reduction in litter size was not as great. Animals whose temperature was raised to 41 degrees C had a much lower incidence of pups with similar defects, and animals whose temperature was raised to 43 degrees C did not survive. A more detailed analysis of the skeletal defects in Experiment 2 showed rib and vertebral malformations that appear to be related to the stage of somite development at the time of exposure. PMID- 8475467 TI - Embryonic development in vitro following short-duration exposure to heat. AB - Gestation day (GD) 10 rat embryos (10-12 somites) were exposed in vitro for 10 to 25 minutes at 42 or 43 degrees C and evaluated 24 hrs later for alterations in growth and specific morphological parameters, using a modified Brown-Fabro (Brown and Fabro: Teratology, 24:65-78, '81) scoring system that allowed evaluation of development relative to gestational age. At 42 degrees C, crown-rump length appeared to be particularly sensitive, responding to only 10 mins exposure. A 15 min exposure resulted in decreased total protein, somite number and morphological score. No system was uniquely sensitive, since all parameters demonstrated some degree of response. Rather, systems affected were those that would be developing most rapidly at this time in gestation. At 43 degrees C, all of the parameters measured were affected by a 10-min exposure. These results demonstrate alterations in vitro after much shorter exposure periods than previously reported on GD10, which may be due, in part, to the use of a modified scoring system that permitted the evaluation of graded individual end point changes relative to gestational age. The response patterns demonstrated a clear temperature- and exposure duration-dependency, with a shift from a more shallow duration-response curve to a more dramatic inhibition of development as temperature increased from 42 degrees C to 43 degrees C. PMID- 8475468 TI - [Substitute drug treatments with methadone]. AB - Methadone maintenance treatment for patients with opiate addiction, started in the Canton of Basel in 1980, today includes more than 600 patients, with a marked increase since 1987 due to a change in inclusion criteria following the spreading of HIV infections. Data from 500 patients, gathered in 1991/92 on sociodemographic and treatment characteristics, emphasize the long-term aspect of the methadone maintenance treatment and the necessity of an intensive psychosocial treatment. PMID- 8475469 TI - [The Basel dependence study]. AB - In a survey of 177 patients of several outpatient departments and private practices in the area of Basel there were 23% with a dependence syndrome according to the diagnostic guidelines of ICD-10. Sedatives and hypnotics were the mostly mentioned psychotropic substances in this group. In a second survey six to twelve months later 80% of the initial study group were reassessed, focusing on referrals of the patients with a dependence syndrome to institutions specialized for the treatment of addiction. In most cases these patients were still treated at the previous institution; there were only a few referrals. Improvements concerning the increase of the referral rate to competent specialized institutions for patients with addiction seems possible by implementation of a decentralized consultation liaison service for outpatient departments, hospitals and also private practitioners in a mobile form. PMID- 8475470 TI - [EMG abnormalities in REM sleep of addicted patients]. AB - EMG abnormalities such as short muscle twitches and marked increase of muscle tone can be identified during REM sleep. We compared the polysomnographic parameters of ten alcoholic patients who were sober and medication-free for at least four weeks, five methadone-substituted politoxicomanic patients (MSP) and ten healthy control patients. The alcoholics and the MSP showed significantly more twitches than the control patients, and the MSP had significantly more tonus increase than the alcoholics and the controlled. The polysomnographic measures differed significantly between the groups in sleep architecture. The alcoholics had significantly less slow-wave sleep (SWS) and more REM sleep, the MSP had a longer REM latency and more of stage 2. Dividing all subjects along the median of the two EMG abnormalities, the group which showed a high number of twitches had significantly less SWS with a compensatory increase of stage 2. The two EMG measures, which were scored additionally, may provide a useful additional information in the differentiation of sleep disturbances in alcoholic and methadone-substituted patients. The interaction between the occurrence of these EMG abnormalities and the other polysomnographic measures in our study needs further clarification. PMID- 8475471 TI - [Beta-carbolines (harman/norharman) are increased in heroin dependent patients]. AB - Endogenous substances resulting from interactions between alcohol and possibly opioid metabolites and neurotransmitters (dopamine, indolamines) are mediators of the pathochemical process towards dependence. Beta-carbolines are increased in alcoholics and--according to our own results--in heroin-addicts. Still unclear is the impact of other psychopathological disturbances like states of anxiety or depression; unclear is also, if it has to be interpreted as state, trait or residual marker of the dependence syndrome. PMID- 8475472 TI - [Acamprosate--a stabilizing factor in long-term withdrawal of alcoholic patients]. AB - In a one-year double-blind-treatment study with acamprosat (six months with and six months without substance) the efficiency of this new medicament could be proved. The number of relapses in the treatment group was significantly lower during the first 30 days with a trend to further 150 days. The substance caused very few side effects. PMID- 8475473 TI - [The importance of work and unemployment for the long-term outcome and rehabilitation of drug dependent patients]. AB - Physicians generally have to deal with therapy and less with rehabilitation of diseases. Employment and the necessary capacity and skills are to be focused on therapeutically in every second drug addict or alcoholic. The continuation of work is an important aim of secondary and tertiary prevention. Some general psychosocial aspects concerning this topic are discussed. PMID- 8475474 TI - [Drugs and violence]. AB - The physician is confronted with victims of drug-related violence in emergency situations, especially in excitations (cocaine) or alcohol-induced intoxications. Moreover, the topic of drug-related violence should not only engage criminologists, specialists in legal and forensic medicine, but also every doctor because of the implications concerning interactions of drugs and society in which the medical profession ist deeply involved. PMID- 8475475 TI - [Future prospects in treatment of drug dependent patients]. AB - During the last 25 years, an important evolution in therapeutic-rehabilitative strategies for drug addicts was observed. Many inputs came from social pedagogics. Great demands are again put on the medical profession in relation to AIDS and substitution programs. In the future the engagement of the medical profession will be required more again, particularly the psychosocial competence of doctors as well as the medical-biological research. PMID- 8475476 TI - Studies on the pharmacokinetics and pharmacodynamics of recombinant hirudin (rHV2 Lys 47) after intravenous and subcutaneous administration in dogs. AB - In recent years, the pharmacological and biochemical characterization of hirudins has taken a major upswing due to the availability of this natural polypeptide in recombinant form. Despite this, the current knowledge on the pharmacokinetics and pharmacodynamics of recombinant hirudin (rH) appears to be incomplete. The present study was designed to investigate the relationship between plasma concentrations of rH with corresponding antithrombin responses after intravenous (i.v.) and subcutaneous (s.c.) administration in dogs. Four male, Mongrel dogs were each injected with an i.v. (bolus) dose (1 mg/kg) of one specific variant of rH, i.e. rH with a lysine residue in position 47 (rHV2-Lys 47). The dogs were injected with a s.c. dose (1 mg/kg) of rHV2-Lys 47 after one week. After each dose, blood was collected at different time intervals, plasma separated and stored at -70 degrees C. Plasma concentrations of rHV2-Lys 47 were determined using an enzyme-linked immunosorbent assay (ELISA) method and pharmacokinetic parameters were determined using standard non-compartmental methods. The ex vivo antithrombin activity of the drug was measured using activated partial thromboplastin time (APTT), calcium-thrombin time (Ca++TT) and a chromogenic anti IIa assay. The results from this study indicate that the pharmacokinetic behavior of rHV2-Lys 47 is strongly influenced by the route of administration. In all three functional assays used, a significant correlation was obtained after i.v. administration between plasma concentrations and corresponding responses over the time period of the study when compared to s.c. administration. The results are indicative of a probable structural and functional modification of this rH variant after s.c. administration which may be responsible for the altered pharmacokinetics and pharmacodynamics after s.c. dosing. PMID- 8475477 TI - Relationship of plasminogen activator inhibitor-1 with plasma insulin, glucose, triglyceride and cholesterol in Chinese patients with diabetes. AB - Plasminogen activator inhibitor-1 (PAI) activity, plasma insulin, glucose, cholesterol and triglyceride (TG) concentrations were determined in 32 Chinese diabetic patients (mean age 61.4 yr) and 41 healthy controls (mean age 64.5 yr) to establish the relationships between these parameters. Insulin, glucose, cholesterol and triglyceride levels were significantly higher in the diabetics, whereas no significant difference of PAI activity was noted between groups. PAI activity was not affected by the increase of plasma insulin, cholesterol, TG or glucose. We have shown that PAI activity in Chinese diabetics was not affected by the common pathologic changes found in diabetes. This might be one of the reasons why fibrinolytic activity is not impaired in Chinese diabetics. PMID- 8475478 TI - Effects of annexin V on the activity of the anticoagulant proteins C and S. AB - The effects of annexin V on the anticoagulant activity of activated protein C (APC) and protein S were examined. Although annexin V did not influence the amidolytic potential of APC, it inhibited both APC and protein S function in a factor Va inactivation assay. Competition experiments demonstrated that annexin V inhibits protein S binding to phospholipid vesicles in a dose-dependent manner. These results demonstrate that annexin V effectively interferes with the anticoagulant arm of the hemostatic system. PMID- 8475479 TI - High levels of histidine-rich glycoprotein and thrombotic diathesis. Report of two unrelated families. AB - Two new families with history of thrombosis and high levels of histidine-rich glycoprotein (HRG) are described. The propositus of family 1 died of massive pulmonary embolism at age 34. Among his relatives, the mother and the maternal grandmother had suffered from deep and superficial vein thrombosis in their youth. A maternal aunt had several episodes of superficial vein thrombosis (SVT). High levels of HRG were found in the mother, three siblings and two nephews. In the second family, the proposita suffered from spontaneous deep vein thrombosis (DVT) at age 24. The paternal grandmother and a paternal aunt had several episodes of SVT and DVT. Also in this family, high levels of HRG cosegregated with thrombotic symptoms. These new families confirm that genetically transmitted high levels of HRG could be associated to familial and juvenile thrombophilia. PMID- 8475480 TI - The effect of a long-acting recombinant hirudin (PEG-hirudin) on experimental disseminated intravascular coagulation (DIC) in rabbits. AB - Reproducible disseminated intravascular coagulation in rabbits was provoked by two intravenous injections 24 hours apart of endotoxin from Salmonella enteritidis. There were mild symptoms of DIC before the second injection which considerably increased thereafter. In detail there was a sharp drop of the platelet count and a considerable diminution of Antithrombin III, of Protein C, Plasminogen and Antiplasmin as well as an appearance of fibrin monomer complexes and an increase of the aPTT. When PEG-hirudin in a single dose of 1 mg/kg BW was given simultaneously with the second injection of endotoxin the following alterations were observed: The drop of the platelet count and of the activities of Antithrombin III, Protein C, Plasminogen and Antiplasmin was significantly less pronounced. The fibrin monomer complexes were lower and the aPTT was less prolonged. The thrombin time, however, as a sign of a direct action of hirudin on thrombin was considerably more prolonged than in the controls. The combined effect of these alterations strongly points in the direction of a favourable influence of PEG-hirudin on the course of DIC. It is of special interest that 6 h after the intravenous injection of PEG-hirudin its full effect on the thrombin time was still detectable. This is apparently due to a longer half-life in circulation of PEG-hirudin than of natural hirudin. PMID- 8475481 TI - Effects of Policosanol on platelet aggregation in rats. AB - Policosanol is the trivial name of a mixture of high molecular weight alcohols isolated from sugar cane, wherein octacosanol is the main component. The effects of Policosanol treatment on rat platelet aggregation were studied. Depending on the dose, Policosanol (5-20 mg/kg, perorally) inhibited the decrease in circulating platelet counts and collagen-induced malondialdehyde concentration in plasma. In rat clotted whole blood thromboxane B2 formation was inhibited by Policosanol (25 mg/kg). Policosanol (50-200 mg/kg, single doses) inhibited ADP induced platelet aggregation in platelet-rich plasma, while lower doses (25 mg/kg) did not change responses to ADP significantly. However, rats treated with this dose (25 mg/kg) for 4 weeks showed a significant inhibition of platelet aggregation in PRP when a submaximal ADP concentrations was administered. PMID- 8475482 TI - Histidine-rich glycoprotein changes during pregnancy in a woman with genetically transmitted high levels of the protein and thrombotic diathesis. PMID- 8475483 TI - [Ethical aspects of keeping companion animals, an empirical and normative analysis]. PMID- 8475484 TI - [Talking about this and that]. PMID- 8475485 TI - [Various aspects and experiences relating to the current control of Newcastle disease]. PMID- 8475486 TI - [Cat flu vaccine with Chlamydia psittaci]. PMID- 8475487 TI - [Effectiveness of kennel cough vaccines]. PMID- 8475488 TI - A fast PCR-SSP method for HLA-DQ generic typing. PMID- 8475489 TI - A novel diabetes-susceptibility HLA haplotype is present in the Croatian population. PMID- 8475490 TI - B*1401 encodes the B64 antigen: the B64 and B65 splits of B14 differ only at residue 11, a buried amino acid. PMID- 8475491 TI - Genes for insulin-dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) of African-Americans. AB - Mapping the MHC-associated susceptibility and resistance factors for insulin dependent diabetes mellitus (IDDM) has been difficult due to the strong linkage disequilibrium within the HLA-DR-DQ region. Previous analyses have suggested that the study of IDDM-associated haplotypes in different races might be useful for identifying the responsible genes. We have performed complete HLA class II genotyping to study susceptibility and resistance to IDDM in 34 randomly selected African-American IDDM patients and 69 ethnically-matched controls. IDDM patients showed highly significant increases of DRB1*0301, DRB1*0401, DRB1*0405, DQA1*0301, DQA1*0302, DQB1*0201 and DQB1*0302. Analysis of DQA1-DQB1 associations showed that DQA1*03 combined with both DQB1*0201 and DQB1*0302 gave the highest odds ratio, suggesting a synergistic effect due to formation of heterodimers encoded both in cis and in trans. Among the subsets of DR4, only DRB1*0401 and DRB1*0405 were increased in diabetic patients. Interestingly, DQB1*0602 and DQB1*0301, which have previously been thought to encode resistance factors in Caucasians, were not significantly decreased and, after removal of known susceptibility haplotypes, were found to have essentially identical frequencies in patients and controls. PMID- 8475492 TI - Structural diversity in the HLA-A10 family of alleles: correlations with serology. AB - The HLA-A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well-defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA-A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the alpha 1 helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475493 TI - A comparative study of HLA-DRB1 typing by standard serology and hybridization of non-radioactive sequence-specific oligonucleotide probes to PCR-amplified DNA. AB - A double-blind study was carried out to evaluate the relative performance and reliability of the PCR/SSOP assay compared to conventional serological typing in identifying HLA-DR alleles. A total of 268 consecutive samples were entered into the study. In 14 (5.2%) of the cases, HLA-DR serology could not be performed due to poor cell viability, while in seven (2.6%) of the cases, PCR/SSOP typing could not be performed due to poor amplification or to contamination with exogenous DNA. Among samples that were successfully typed by both methods, serologic typing correctly identified 455/465 (97.9%) DR antigens, while PCR/SSOP correctly identified 464/465 (99.8%) DR alleles (p = 0.0117, McNemar's test). The majority of discrepancies in serologic typing resulted from a lack of discriminative alloantisera to identify DR6 or DR103. For the overall sample set (N = 268), serology provided accurate results in 244 (91.0%) cases, while PCR/SSOP provided accurate results in 260 (97.0%) cases (p = 0.0037). The results of this study demonstrate that PCR/SSOP typing for HLA-DRB1 alleles provides results that are equal to or surpass serological typing for HLA-DR antigens. In addition, the PCR/SSOP approach offers the advantages of better reagent availability, lower cost, more rapid turn-around time, and greater accuracy, all of which would warrant its use as an HLA typing method of choice. PMID- 8475494 TI - Transcription analysis of non-HLA genes within or flanking the class II region in a B-cell line from an HLA-SCID patient. PMID- 8475495 TI - A new HLA-DR4 allele with a DR11 alpha-helix sequence. PMID- 8475496 TI - Teratogenic phase specificity of butyl benzyl phthalate in rats. AB - Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0.6, 0.75 or 1.0 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. While treatment with BBP on days 7-9 or 13-15 at doses of 0.75 and 1.0 g/kg was significantly teratogenic, no evidence of teratogenicity was detected when BBP was given on days 10-12. The incidence of malformed fetuses was proportional to the dose of BBP. Treatment on days 7-9 with BBP at doses of 0.75 g/kg and above caused a significant increase in the number of skeletal malformations, such as fusion of the cervical vertebral arches and deformity of the thoracic vertebrae, but neither external nor internal malformations. Treatment on days 13-15 with two higher doses of BBP resulted in a significantly increased incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The highest incidence of malformed fetuses occurred after treatment with BBP on days 13-15. It could be concluded that the susceptibility to the teratogenicity of BBP varies with the developmental stage at the time of administration. PMID- 8475497 TI - Strain differences in the response of Fischer 344 and Sprague-Dawley rats to monocrotaline induced pulmonary vascular disease. AB - The pyrrolizidine alkaloid (PA) monocrotaline (MCT) is thought to be activated in the liver to monocrotaline pyrrole (MCTP) which is then transported to the lungs where it causes a pulmonary vascular syndrome characterized by elevated pulmonary artery pressure and right ventricular hypertrophy. We have found that, as opposed to Sprague-Dawley (SD) rats, Fischer 344 (F344) strain rats are resistant to the ventricular hypertrophy and pressure changes induced by MCT. To determine whether this strain difference might be related to differences in hepatic activation of MCT to MCTP, we compared the response of SD and F344 rats to treatment with MCT or MCTP. We determined right ventricular pressure and ventricular weight ratios with each treatment for each strain. We also compared subjective lesion scores of histopathologic changes characteristic of MCT pneumotoxicity. Sprague-Dawley rats treated with either MCT or MCTP had elevated right ventricular pressures (Control 13 +/- 1 mmH2O, MCTP 29 +/- 3 mmH2O, MCT 24 +/- 2 mmH2O) and increased right ventricular weight ratio (RV/LV + S) of 0.30 +/- 0.01 (Control), 0.44 +/- 0.05 (MCTP), 0.44 +/- 0.02 (MCT). Histopathologic evaluation demonstrated that significant alveolar septal fibrosis, edema and type II cell hypertrophy was induced by both PAs in both rat strains but that F344 rats had significantly less vascular medial hypertrophy and adventitial inflammation than SD rats. MCTP treated SD rats had similar vascular and parenchymal alterations as those treated with MCT but with a lesser inflammatory component. We conclude that the strain differences in cardiac and pulmonary vascular responses to MCT also occur with MCTP treatment. This, combined with the similarity in alveolar parenchymal response to both PAs in both strains, suggests that these differences are related to the pulmonary vascular response rather than differences in hepatic metabolism. PMID- 8475498 TI - Protection against paraquat-induced toxicity with sulfite or thiosulfate in mice. AB - The toxicity of the herbicide paraquat in mice, measured by the single dose LD50 after 7 days, was significantly decreased by coinjection of thiosulfite (1 g/kg; one time per day for 3 days) or sulfite (0.2 g/kg; one time per day for 3 days). However, the toxicity of paraquat was not changed by coinjection of sulfate (1 g/kg; one time per day for 3 days). The body weight of mice was significantly decreased by paraquat treatment (30 mg/kg, i.p.). However, the decrease of body weight was abolished by coinjection of thiosulfate or sulfite but not by coinjection of sulfate. On the other hand, paraquat significantly decreased reduced glutathione contents in liver. The depletion of the glutathione contents was also abolished by coinjection of thiosulfate or sulfite but not by coinjection of sulfate. These results suggest that the preventive effect against paraquat-induced toxicity with thiosulfate or sulfite may involve the glutathione dependent detoxication in mice. PMID- 8475499 TI - Extrarenal and direct renal actions of atractyloside contribute to its acute nephrotoxicity in pentobarbital-anesthetized dogs. AB - Acute extrarenal and renal changes were noted following the intravenous administration of atractyloside (ATR) (12.97 and 32.40 mumol/kg) to spontaneously respiring, pentobarbital-anesthetized dogs. Severe hypoglycemia, respiratory depression and hypoxemia developed within 2 h. These extrarenal changes were accompanied by adverse changes in renal function, ultrastructural damage to S1, S2 and S3 cells of the proximal tubule and to thick ascending limb cells and an impaired ability of the kidneys to respond to a known diuretic--ethacrynic acid (EA). Mechanical ventilation of ATR-treated pentobarbital-anesthetized dogs circumvented the development of hypoxemia and all but eliminated the toxicity to S3 and thick ascending limb cells, thereby establishing that ATR's extrarenal actions contributed to its nephrotoxicity. On the other hand, direct renal actions of ATR were evident following its administration into the renal artery; certain important extrarenal effects were minimized, while adverse changes in renal function and ultrastructure of S1 and S2 cells were noted primarily in the ipsilateral kidney. The high degree of variability associated with ATR's systemic toxicity was confirmed and a similar degree of variability in its renal toxicity was established. Our results emphasize the importance of evaluating the extrarenal effects produced by any toxicant when determining its nephrotoxic potential. PMID- 8475500 TI - Examination of the structure-toxicity relationships of L-cysteine-S-conjugates of halogenated alkenes and their corresponding mercapturic acids in rat renal tissue slices. AB - Rat kidney slices were produced using a modified version of a mechanical tissue slicer. The slices were incubated with various concentrations of L-cysteine conjugates and mercapturic acids of halogenated alkenes in a submersion incubation system. The slices showed a time- and concentration-dependent toxicity to the nephrotoxic conjugates. The five L-cysteine conjugates tested: S-(1,2 dichlorovinyl)-L-cysteine (1,2-DCVC), S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(1-chloro-1,2,2-trifluoroethyl)-L-cysteine (CTFEC), S-(1,1-dichloro-2,2 difluoroethyl)-L-cysteine (DCDFEC) and S-(1,1-dibromo-2,2-difluoroethyl)-L cysteine (DBDFEC) were more toxic compared to the corresponding mercapturic acids. Comparing the in vitro toxicity data with the in vivo data for the same compounds results in similar ranking for the relative nephrotoxicity of the conjugates. PMID- 8475501 TI - Reduction of hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is due to decreased mRNA levels. AB - We have previously shown that the rate of hepatic gluconeogenesis is reduced in TCDD-treated rats and that this decrease in carbohydrate production is associated with a dose-dependent reduction of the activity of PEPCK, the rate limiting enzyme of gluconeogenesis. This derailment of glucose metabolism has been suggested to be the critical lesion in acute TCDD toxicity. To further elucidate the mechanism of decreased PEPCK activity we performed Northern blot analyses using a cDNA probe complementary to a portion of the mRNA coding for PEPCK. We have demonstrated that 4 and 8 days after TCDD treatment (125 micrograms/kg, p.o.) liver PEPCK mRNA in Sprague-Dawley rats was decreased to very low levels as compared to vehicle-treated and pair-fed control animals. This decline of PEPCK mRNA was paralleled by decreased levels of PEPCK protein, as revealed by Western blot analyses and was accompanied by a reduction in the enzymatic activity of PEPCK. These results indicate that the decrease of PEPCK activity by TCDD is most likely the result of decreased expression of the PEPCK gene. These together with previous results also suggest that many of the physiological responses occurring in TCDD-treated animals (reduced feed intake, decreased insulin, increased corticosterone, increased glucagon and cAMP levels) which would normally stimulate PEPCK gene expression, are ineffective. Furthermore tryptophan 2,3 dioxygenase (TdO) activity, which is regulated in a very similar fashion to PEPCK activity, is also reduced after TCDD treatment, suggesting a common mechanism by which TCDD alters the regulation of these enzymes. P-450 1A1 mRNA and related EROD activity were maximally induced under the conditions of these experiments and represent a positive control for TCDD-related alterations of gene expression. However, because of differences in the dose-response characteristics of TCDD induced reduction of PEPCK activity and induction of EROD activity an involvement of the Ah receptor in the reduction of PEPCK activity cannot be postulated. PMID- 8475502 TI - Assessment of genotoxicity of two anti-parkinsonian drugs (selegiline hydrochloride and bromocriptine mesylate) in vivo in mouse bone marrow cells. AB - Selegiline hydrochloride (1-deprenyl) and bromocriptine mesylate (2-bromo-alpha ergocryptine) are two drugs that have shown considerable promise in the treatment of Parkinson's disease. The in vivo mouse bone marrow micronucleus assay was used to examine their clastogenic and cytotoxic potential in human clinical dose range. Our results indicate that both drugs failed to induce significant number of micronuclei and were not cytotoxic at any of the doses tested, in vivo in mouse bone marrow cells, at doses as high as 16-times the clinical dose used in humans. PMID- 8475503 TI - Production of polyclonal antibodies against 1,1'-ethyliden bis[L-tryptophan] (EBT), a potential contaminant causing eosinophilia-myalgia syndrome (EMS). AB - Eosinophilia-myalgia syndrome (EMS) is thought to be caused by the intake of contaminated L-tryptophan products. 1,1'-Ethyliden bis[L-tryptophan] (EBT) is one of the contaminants in the L-tryptophan products and is thought to be a possible cause of EMS. In the present study we report that anti-EBT antibodies are generated by immunizing rabbits with the low molecular weight substance, EBT (molecular weight 434). These antibodies may be available tools for elucidating the mechanisms responsible for the outbreak and/or development of EMS. PMID- 8475504 TI - The effects of chronic lead exposure on reactivity to frustrative nonreward in rats. AB - Prior to straight runway training two groups of rats received lead exposure (500 ppm via the drinking water) for 106 days. Two additional groups of animals received access to plain tap water. An 80-trial runway acquisition phase followed an initial 60-day fluid exposure phase. During acquisition one lead-exposed group and one water-exposed group received 50% partial reinforcement training, while the remaining animals received continuous reinforcement training. An 80-trial extinction phase immediately followed acquisition. Acquisition results were characterized by superior performance by the continuous reinforcement animals. The partial reinforcement animals took significantly longer to extinguish the alleyway response than did the continuous reinforcement animals. Moreover, the lead-exposed, partial reinforcement animals took longer to extinguish in the goal section of the runway than did the water-exposed, partial reinforcement animals. Conversely, the lead-exposed, continuously reinforced animals displayed significantly more rapid goal-measure extinction than did the water-exposed, continuously reinforced animals. When interpreted by the classic frustration theory [1,2], these latter two findings are supportive of a heightened emotional reaction being promulgated by lead exposure. PMID- 8475505 TI - Zinc protection against cadmium-induced destruction of the monolayer of cultured vascular endothelial cells. AB - The effect of zinc on the destruction of vascular endothelial cell monolayer caused by cadmium was investigated using bovine aortic endothelial cells in a culture system. It was histologically revealed that cadmium-induced de endothelialized area formation was markedly prevented by zinc. Zinc prevented cadmium-induced detachment of [3H]thymidine-labeled endothelial cells from the monolayer. Although cadmium increased the activity of lactate dehydrogenase in the medium, a marker of nonspecific cell damage, zinc markedly suppressed it. On the other hand, zinc significantly prevented cadmium-induced decrease in the incorporation of [3H]thymidine into the acid-insoluble fraction of the growing cells. From these results, it was suggested that impairment of the endothelial cell monolayer caused by cadmium is protected by zinc; this protection was postulated to be due to both a reduction of the cell detachment caused by cadmium induced nonspecific cell damage and a decrease in cadmium inhibition of the cell proliferation which would help the repair of de-endothelialized areas. PMID- 8475506 TI - Allylamine enhances c-Ha-ras protooncogene expression in rat aortic smooth muscle cells. AB - Studies were conducted to evaluate the mechanisms involved in the deregulation of proliferative control induced by allylamine (AAM) in rat aortic smooth muscle cells (SMCs). Subcultured SMCs from animals treated with AAM (70 mg/kg) or tap water for 20 days were processed for measurements of [3H]thymidine incorporation and c-Ha-ras mRNA levels. Pre-confluent AAM cells stimulated with 10% fetal bovine serum exhibited enhanced mitogenic responsiveness relative to control cells. Decreased [3H]thymidine incorporation was observed in post-confluent cultures of both cell types relative to pre-confluent counterparts. A 5-fold increase in c-Ha-ras transcript levels was observed in pre-confluent/cycling cultures of AAM cells relative to controls. C-Ha-ras expression was markedly reduced in post-confluent cultures of both cell types as compared to pre confluent counterparts. No difference between control and AAM cells was observed during G1-synchronization of pre- or post-confluent cultures. These results suggest that the enhanced proliferative capacity induced by AAM is associated with alterations in cell cycle-related expression of the c-Ha-ras protooncogene. PMID- 8475507 TI - Selenium lethality: role of glutathione and metallothionein. AB - Male Sprague-Dawley rats (200-300 g) were pretreated (i.p.) with diethylmaleate (DEM; 3.1 mmol/kg) or propylene glycol (PG). After 1 h, three PG and three DEM groups received saline or sodium selenite (Se: 0.8 or 1.6 mg/kg) i.p. Eighty to one hundred percent mortality occurred within 3 h after Se in DEM-pretreated groups. Except for one PG and one DEM group, which were sacrificed after 1 h, the remaining groups received saline or Se (1.6 mg/kg) 25 h after pretreatment. No mortality occurred within 3 h after Se. Liver and kidney GSH decreased at 1 h, while liver MT increased at 28 h. The changes are related to Se-induced lethality. PMID- 8475508 TI - Prophylactic effect of methylprednisolone against cisplatin-induced nephrotoxicity in rats. AB - Male Sprague-Dawley rats were intravenously injected with 6.5 mg/kg of cisplatin combined with a subcutaneous methylprednisolone (MP) injection to study the prophylactic effects of steroid hormone on cisplatin-induced nephrotoxicity. In Expt. 1, the rats were injected twice with either 10, 20 or 50 mg/kg of MP4 and 0 h prior to the cisplatin injection and in Expt. 2, they were given a single injection of 100 mg/kg of MP either 24, 4, 2 or 0 h prior to the cisplatin injection. In Expt. 1, elevations of the BUN and serum creatinine levels caused by the cisplatin were dose-dependently inhibited by the administration of MP. In the second experiment, BUN and serum creatinine levels in rats which were pretreated with MP 4 or 2 h prior to the cisplatin injection were significantly lower than those in rats which received cisplatin alone. Our preliminary results suggest that pretreatment with MP is an effective means of protection against cisplatin-induced nephrotoxicity. PMID- 8475509 TI - Subcellular and gel chromatographic distribution of manganese in the mouse brain: relation to the chemical form of chronically-ingested manganese. AB - The subcellular distribution of manganese and the binding characteristics of manganese to protein in the mouse brain were examined on G-75 Sephadex gel columns. Four manganese compounds were included at 2 g/kg in each food eaten by ddY mice for 12 months. The cerebral cortex manganese concentrations in the virtually insoluble manganese compounds were significantly higher than those in the control group. The brain striatal subcellular distribution and gel chromatographic profiles of manganese were similar among the divalent manganese compounds. On the contrary, the behaviour of MnO2 was little different from the divalent manganese compounds. There was more manganese associated with fast migrating ligands in the striatal cytosol of the manganese-exposed group than in the control groups. PMID- 8475510 TI - Three generation toxicity study of butylated hydroxytoluene administered to mice. AB - Butylated hydroxytoluene (BHT) was administered to mice, from 5 weeks of age of the F0 generation to the weaning of the F2 generation, in the diet at levels of 0 (control), 0.015, 0.045, 0.135, and 0.405%, and some reproductive and neurobehavioural parameters were measured. There was no consistent significant effect on number of litters, litter size, and litter weight at birth for each generation. The body weight of the pups of the 0.015% BHT group was increased at birth and during the lactation period for each generation. In the F2 generation, the body weights of the pups of other treatment groups were increased during the lactation period, particularly at postnatal day (PND) 21. In the neurobehavioural parameters, a few parameters were increased in treatment groups; i.e., surface righting at PND 7 in the F1 generation, surface righting at PND 4 and negative geotaxis at PND 7 in the F2 generation. The dose levels of BHT in this study showed little adverse effect on reproductive and neurobehavioural parameters on mice. PMID- 8475511 TI - Induction of hepatic polyamines by di(2-ethylhexyl)phthalate in rats. AB - Wistar male albino rats, weighting 125-150 g, were administered di(2 ethylhexyl)phthalate (DEHP) orally at 250, 500, 1000 and 2000 mg/kg body weight diluted in groundnut oil consecutively for 14 days. Spermidine and spermine of the livers were separated by thin-layer chromatography and quantitatively estimated by spectrofluorometry. DEHP exposure led to a significant increase in the absolute and relative weights of the liver at the 1000 and 2000 mg/kg dose levels. Spermidine and spermine levels were induced significantly in a dose dependent manner. The increase in spermidine was greater as compared to that of spermine. Our results manifest that DEHP significantly induces the levels of hepatic polyamines. PMID- 8475512 TI - Effect of protein kinase-C inhibitor on estradiol-induced deoxyribonucleic acid synthesis in rats. AB - Effect of polymyxin B (PMB, protein kinase C inhibitor) on estradiol-induced thymidine incorporation into uterine DNA was studied in ovariectomized rats. Administration of estradiol to ovariectomized rats enhanced thymidine incorporation to uterine DNA 15-fold. Pretreatment of rats with PMB 1 hour before the administration of estradiol had a dose-dependent inhibitory effect on estradiol induced response. PMB had no effect on the basal levels of thymidine incorporation. The inhibitory effect of PMB was also observed with prostaglandin F2 alpha (PGF2 alpha)-induced thymidine incorporation. Time-course experiments indicate that PMB was effective in alleviating estradiol-induced response when administered 1 hour before or 5 minutes after estradiol administration. However, PMB did not antagonize estradiol-induced response when administered at 2, 4, 8, and 12 hours after estradiol administration. Polymyxin E (PME), which differs from PMB by one conservative amino acid substitution in the ring structure and is devoid of PKC activation, did not decrease estradiol- or PGE2 alpha-enhanced thymidine incorporation. It is concluded that estradiol-induced protein kinase-C activation may play a role in the stimulation of thymidine incorporation into uterine DNA and that this effect occurs within the first 2 hours of estradiol administration. PMID- 8475513 TI - Synthesis and biochemical studies of estrone sulfatase inhibitors. AB - The synthesis and biochemical evaluation of estrone sulfatase inhibitors are described. Inhibitors were designed through modifications of the substrate estrone sulfate. An in vitro assay using the microsomal fraction isolated from human term placenta was used to evaluate sulfatase inhibitory activity. All the inhibitors (except sulfonyl chloride analog) exhibited low inhibitory activities in the screening assay. Sulfonyl chloride analog is a strong inhibitor, which caused 91.5% inhibition of the enzymatic activity at 300 microM. PMID- 8475514 TI - 3 alpha-hydroxy-5 alpha-pregnan-20-one is the only active anesthetic steroid in anesthetized mouse brain. AB - It was demonstrated that the anesthetic steroid 3 alpha-hydroxy-5 alpha-pregnan 20-one mediates the loss of the righting response (LRR) in mice, in contrast to its metabolites, which are formed in vivo. To reach these conclusions, it was necessary to quantitate levels for 3 alpha-hydroxy-5 alpha-pregnan-20-one and its metabolites at the time of LRR. Methods were used that blocked the production of essentially all of the metabolites. Chromatography of brain extracts by thin layer chromatography and high-performance liquid chromatography after anesthesia with 3 alpha-hydroxy-5 alpha-[3H]pregnan-20-one showed only a single peak that corresponded to 3 alpha-hydroxy-5 alpha-[3H]pregnan-20-one. PMID- 8475515 TI - Steroids 51. An improved synthesis of ORG 2058 and the synthesis of [3H]ORG 2058. AB - 16 alpha-Ethyl-21-hydroxy-19-norpregn-4-ene-3,20-dione (ORG 2058) is a ligand widely used in progesterone receptor assays. An improved synthesis of the compound is reported, starting from norethisterone acetate. The preparation of the tritiated radioligand [3H]ORG 2058 is also described. PMID- 8475516 TI - Synthesis of potential C27-intermediates in bile acid biosynthesis and their deuterium-labeled analogs. AB - In connection with studies of alternative pathways in bile acid biosynthesis, potential intermediates in a pathway starting with 27-hydroxylation of cholesterol have been prepared in natural and deuterated forms. Established methods were used to prepare 27-hydroxycholesterol and 3 beta-hydroxy-5 cholestenoic acid. Clemmensen reduction of kryptogenin in unlabeled and deuterated solvents yielded 27-hydroxy-cholesterol and 16-oxo-5-cholestene-3 beta,27-diol, which were separated by adsorption chromatography on Unisil. The labeled 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid derived from it consisted of molecules with seven (50%), six (20%), and eight (20%) deuterium atoms, and unlabeled molecules were not detected. The acetates of 27 hydroxycholesterol and methyl 3 beta-hydroxy-5-cholestenoate were 7 alpha hydroxylated in a copper-catalyzed reaction with tert-butylperbenzoate, and the products were purified by chromatography on Unisil. The 7 beta-epimers were obtained as side products. Labeled 3 beta,7 alpha-dihydroxy-5-cholenoic acid was prepared in the same way from 3 beta-hydroxy-5-[2,2,4,4,23-2H5]-cholenoic acid. The 3-oxo-delta 4 analogs of the 3 beta-hydroxy-delta 5 compounds were prepared by oxidation with cholesterol oxidase. The labeled products had the same isotopic composition as the starting materials. Gas chromatographic retention indices and mass spectral characteristics of the trimethylsilyl ether derivatives of the neutral steroids and the methylated acids are given for all compounds. PMID- 8475517 TI - Sex-specific response of bone cells to gonadal steroids: modulation in perinatally androgenized females and in testicular feminized male rats. AB - We have found previously that rat diaphyseal bone in vivo, as well as rat embryo calvaria cells in culture, show a sex-specific response to gonadal steroids in stimulation of creatine kinase (CK)-specific activity, and the rate of [3H]thymidine incorporation into DNA; male-derived cells responded only to testosterone or to dihydrotestosterone (DHT), whereas female-derived cells were stimulated exclusively by estradiol (E2). In this study, we tested whether developmental hormone manipulation could alter this sex specificity. We showed that diaphyseal bone of prenatally or neonatally androgenized female rats responds to a single injection of either E2 (5 micrograms/rat) or DHT (50 micrograms/rat) at 3-4 weeks postandrogenization. This response of androgenized female diaphyseal bone to androgen gradually declines; 3 months posttreatment, diaphyseal bone no longer responds to DHT and reverts to its original sex specificity. Rat embryo calvaria cell cultures prepared from female fetuses androgenized in utero showed the same lack of hormonal specificity, that is, the cells responded to both E2 (30 nM) or DHT (300 nM). Cells derived from the male siblings of the prenatally androgenized rats were not affected and responded only to DHT. In contrast to experiments in utero, in vitro administration of testosterone (1 microM) or E2 (1 microM) to calvaria cells from female embryos failed to cause the cells to respond to DHT. Androgen receptor-deficient (Tfm) male rats, which have approximately 10% of the normal response to androgens, also showed a response to both testosterone and E2 in comparison to their normal male siblings, whose bones responded only to androgens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475518 TI - New delta 8- and delta 8(14)-5 alpha,6 alpha-epoxysterols from the marine sponge Spongia officinalis. AB - Six new delta 8- and delta 8(14)-5 alpha,6 alpha-epoxysterols (1-6) have been isolated from a collection of the Mediterranean sponge Spongia officinalis. The structures of the new metabolites, isolated as diacetate derivatives, have been determined by spectral analyses and an x-ray diffraction experiment performed on the diacetyl derivative of 1. PMID- 8475519 TI - An improved synthesis of 18-norandrost-4-ene-3,17-dione. AB - We describe the synthesis of 13 beta- and 13 alpha-H-18-nor-androst-4-ene-3,17 dione (1a and 1b) from 18-hydroxyprogesterone (18-->20) hemiketal, via the 18 acetoxy-17 beta-hydroxyandrost-4-en-3-one formed by a modified Baeyer-Villiger reaction. Saponification of 18-acetoxyandrost-4-ene-3,17-dione with sonication, then retroaldolization in the presence of a formaldehyde trap, methone, afforded the mixture of 1a and 1b with 80% yield in a "one-pot" procedure and at room temperature. This yield was greatly improved, compared with the already published procedure. PMID- 8475520 TI - Sexual networking in provincial Thailand. AB - Thailand is currently experiencing a major HIV epidemic, spread primarily through heterosexual contact. Patronage of prostitutes is relatively common. In-depth, open-ended interviews were conducted in a Central Thai province with a purposive sample of 181 urban men who had had sexual relations with at least two different women during the prior year. Additional qualitative information is provided by interviews with 50 women. The most common network pattern for men was a combination of commercial and noncommercial sexual relationships. Men reported that they commonly used condoms when they engaged in sex with prostitutes, but condom use was lowest for men who were the most frequent patrons. In noncommercial, nonmarital relationships, men screen partners for risk rather than practice safe sex, and condom use is generally low. Persons involved in noncommercial sexual networks are largely unaware that their partner may link them to a larger network of sexual contacts and associated risks of HIV infection. Men who have both commercial and noncommercial sexual partners can be found throughout the social strata. A program that focuses only on the closed commercial sex network will address only partially the real risk situations. PMID- 8475521 TI - Human rights and reproductive choice. AB - A central challenge in developing reproductive health strategies is giving real meaning to the right of couples and individuals to determine, freely and responsibly, the number and spacing of their children. This article places the right of reproductive choice in legal and historical contexts, highlights salient issues that arise in trying to formulate international standards for its enforcement, and examines two particularly thorny issues: the tension between demographic priorities and reproductive choice and the tension between international standards and local custom/religion. The article calls on health professionals to participate actively in the elaboration of reproductive rights, both through their immediate work in the health-care field and through involvement in the international policymaking process that will take place in three upcoming international conferences. PMID- 8475522 TI - Population policy in South Africa. AB - This report examines the current state and likely future directions of population policy in South Africa with particular reference to family planning activities set against the background of apartheid and its demise. In the apartheid era, population policy was perceived by most blacks as an instrument for the control of their number and movements. Recently, policy has been adjusted by the national Population Development Program in response to the changing sociopolitical situations in the country. A national post-apartheid population policy is likely to retain many of the components of this new program. However, a future nonracist and democratic society would probably invite a review of population activities in the country and raise wider issues concerning rationales, organization, and strategies for the delivery of family planning in South Africa. PMID- 8475523 TI - The client's view of high-quality care in Santiago, Chile. AB - The meaning of quality of care for the women who receive reproductive health services at a family planning and maternal and infant care clinic in Santiago, Chile, was examined to describe the clinic's service from the women's point of view. A participatory research project with the staff of the clinic was conducted. The central part of that study, reported here, consisted of interviews with 60 of the 330 women who came to the clinic during two weeks in June 1991. The women defined high quality of care as "being treated like a human being." Among specific elements of care they identified were cleanliness, promptness and availability of service, time made available for consultation, learning opportunities for themselves and their partners, and cordial treatment. Clients' view of quality of care must be supplemented by professional judgments about how well services meet clients' needs. But the client's view is determinant if improvements are to result in greater acceptance and sustained use of the services offered. The issues identified by the clients involve only minor costs for the clinic. PMID- 8475525 TI - Why do projections of the cost of family planning differ so widely? PMID- 8475524 TI - Sexual activity, family life education, and contraceptive practice among young adults in Banjul, The Gambia. AB - This report presents results from a 1986-87 two-stage probability sample survey of 2,507 young men and women aged 14-24 living in the Greater Banjul region of The Gambia. Although premarital sexual activity was common and began at an early age, lack of knowledge and limited access to modern contraceptives were obstacles to the use of family planning. Of all ever sexually active single persons, only 21 percent of the young women and 7 percent of the young men had practiced contraception at the time of first intercourse. Almost half of the sexually active young adults had ever used contraceptives, with oral contraceptives and condoms being the methods most widely known and used. Results of logistic regression analyses show that attendance at family life education lectures in school had significant positive relationships to both knowledge and use of contraceptives among the young people surveyed. The study presents encouraging evidence that acceptance of modern contraceptive use is beginning to take hold among young people in urban Banjul. PMID- 8475526 TI - Peru 1991/1992: results from the Demographic and Health Survey. PMID- 8475527 TI - Suicide prediction revisited. AB - Data from a 1983 prospective study of suicide in a cohort of 4800 psychiatric inpatients were reanalyzed using logistic regression, which is more appropriate for a binary outcome. The results were the same as in the previous study: too few of the subsequent suicides were identified and there were too many false positives to make this procedure useful. Several additional "artificial" logistic regression analyses were done: one series randomly removed increasing numbers of nonsuicide cases to increase the base rates; another series added an increasingly powerful hypothetical "test." Both of these maneuvers helped, but fell well short of perfection. PMID- 8475528 TI - Dysfunctional attitudes and suicidal ideation in psychiatric outpatients. AB - To determine if specific sets of dysfunctional attitudes were related to suicidal ideation, the 100-item Dysfunctional Attitude Scale (DAS) was administered to 908 psychiatric outpatients along with the Beck Depression Inventory (BDI), Hopelessness Scale (BHS), Self-Concept Test (BST), and Scale for Suicide Ideation (SSI). The SSI was used to classify the outpatients into 97 (10.7%) suicide ideators and 811 (89.3%) nonideators, and the DAS was scored for nine subscales described by Beck, Brown, Steer, and Weissman (1991). None of the DAS subscales discriminated the ideators and nonideators or was significantly related to SSI total scores of the suicide ideators after controlling for sex, age, diagnosis of a mood or panic disorder, comorbidity, presence of a personality disorder, a history of a past suicide attempt, the BDI, the BHS, and the BST. The contributions of sets of dysfunctional attitudes for identifying and explaining suicidal ideation were overshadowed by a history of a past suicide attempt and hopelessness. PMID- 8475529 TI - Narcissistic crises of aging and suicidal despair. AB - After reviewing some of the dangers inherent in oversimplifying the nature of suicide for public education purposes, a model (the "wedding-cake model") of elderly suicide is outlined. This model is derived from a community-based psychological autopsy study. It is hypothesized that elderly persons who die by suicide have a lifelong character fault that remains invisible until aging life changes force the issue into the open. PMID- 8475530 TI - Suicide causation: pies, paths, and pointless polemics. AB - Most people readily agree that suicide is caused by a complex web of many different factors. However, for many people the concept of a single event resulting from the combined effect of a constellation of different factors (multiple causation) is imperfectly understood. Unfortunately, a naive understanding of multiple causation can lead to needless arguments about what "really" causes suicide, and pointless debate about the "right" point for preventive intervention. In this paper, I review several simple conceptual models of multiple causation as they relate to suicide prevention. I suggest that a more explicit understanding of the nature of multiple causation has the potential to obviate some of these misguided arguments and to facilitate cooperative prevention efforts among person who choose to apply their energies at different points in the causal chain of suicide. PMID- 8475531 TI - Factor composition of the Suicide Intent Scale. AB - An exploratory analysis of the Suicide Intent Scale was performed on a sample of 98 psychiatric inpatients who had made suicide attempts. The factor analysis was performed using a method for polychotomous data, and resulted in a two-factor solution. The Lethal Intent factor contained items pertaining to the subjective level of lethal intent, while the Planning factor contained items largely related to objective planning for the attempt. Preliminary analysis of these factors suggest that the Suicide Intent Scale can be used to evaluate two separate aspects of suicidal behavior. PMID- 8475532 TI - Adolescent suicidal risk: psychological, problem solving, and environmental factors. AB - This study examined the life stress and problem-solving interactional model of suicide proposed by Clum, Patsiokas, and Luscomb (1979). Thirty-three hospitalized suicidal adolescents were compared with 21 adolescents hospitalized for other psychiatric problems and with 89 controls. The assessment battery was composed of psychological measures, problem-solving measures, and environmental and family measures. The discriminant analyses revealed that the suicide group could be discriminated from the psychiatric control group but not from the high school control group. Unexpectedly, life stresses did not contribute to the identification of current suicide risk. The results suggest the importance of assessing suicide risk at the time of admission to minimize any subsequent changes in the risk group. PMID- 8475533 TI - Dreams and suicide. AB - The dreams of suicidal patients are contrasted to those of nonsuicidal, depressed patients. The dreams of suicidal patients often reveal wishes for revenge, punishment, reunion, fusion, and rebirth. Confusions between the patient's body and that of others are suggested by the dreams of some suicidal patients. Dreams in suicidal individuals may portray disintegration of the self (self-state dreams). The phenomenon of transparency in suicidal dreams is discussed as it pertains to Rorschach studies. PMID- 8475534 TI - The media and suicide: a nonadditive model, 1968-1980. AB - Unlike previous work, the present investigation tests a nonadditive model of the suggestion/imitation. Suicide stories are predicted to have the greatest effect on suicide in times of high suicidogenic conditions. The latter are measured in terms of unemployment. Data on the American monthly suicide rate are analyzed using Cochrane Orcutt techniques. While support was found for the nonadditive model based on an interaction effect between media stories and the rate of unemployment, it did not prove more powerful than an additive model. Future work is needed, however, for a systematic testing of the nonadditive thesis. PMID- 8475535 TI - Suicide in mental disorder. PMID- 8475536 TI - Suicide deaths in males during morning hours. PMID- 8475537 TI - Enhancement of allograft survival by combination RS-61443 and DUP-785 therapy. AB - Current maintenance immunosuppressive therapy consists of cyclosporine in combination with prednisone and azathioprine. Unfortunately these agents are associated with significant side effects resulting in post-transplant morbidity and mortality. Therefore, the search for new immunosuppressive agents is essential, not only to improve the results after organ transplantation but equally important to reduce morbidity. Recently two new antiproliferative drugs, RS-61443 (RS) and DUP-785 (DUP), have become available. RS (mycophenolate mefotil), a semisynthetic derivative of mycophenolic acid, inhibits purine de novo synthesis by noncompetitively and reversibly inhibiting inosine monophosphate dehydrogenase. DUP (brequinar sodium) inhibits pyrimidine synthesis by reversibly inhibiting dehydroorotate dehydrogenase. We evaluated subtherapeutic combination RS and DUP therapy in the rat (ACI-->LEW) heterotopic heart allograft model. Median graft survival with no treatment, RS (20 mg/kg/day), DUP 3 mg/kg (3x /week), or DUP 6 mg/kg (3x/week) was 6.5, 11.5, 9.5 and 14.5, respectively. Median graft survival with combination therapy (RS 20 mg/kg, DUP 6 or 3 mg/kg 3x/week) was 133 days and 121 days, respectively. Furthermore, mean survival following cessation of all therapy at 100 days posttransplant was dramatically prolonged to 65.7 +/- 43.8 days in animals receiving combination therapy (RS 20 mg/kg/day, DUP 6 mg/kg 3x/week). Despite the potent immunosuppressive activity, recipients treated with combination therapy demonstrated no side effects and gained body weight during the treatment. To determine if low-dose combination therapy was effective in reversing ongoing rejection, treatment was delayed until the 5th postoperative day. Four of 5 recipients (80%) receiving RS monotherapy (60 mg/kg/day), 5 of 5 recipients (100%) receiving DUP monotherapy (12 mg/kg/day), and 4 of 5 grafts (80%) receiving combination therapy (RS 40 mg/kg/day and DUP 6 mg/kg/day) survived over 21 days. Our results demonstrated that combination therapy significantly prolonged graft survival, and that the progression of advanced rejection was halted immediately. RS and DUP combination may provide a potent immunosuppressive therapy in clinical transplantation. PMID- 8475538 TI - Prolongation of canine intestinal allograft survival with RS-61443, cyclosporine, and prednisone. AB - The efficacy of RS-61443 and cyclosporine utilized either alone or in combination was assessed in both a segmental heterotopic and total orthotopic canine intestinal transplant model. Twenty-eight dogs underwent segmental (150-cm) heterotopic intestinal transplants and five dogs total orthotopic transplants. Five heterotopic groups were compared: group 1, no immunosuppression; group 2, cyclosporine and prednisone; group 3, RS-61443, cyclosporine and prednisone; group 4, RS-61443 and prednisone; and group 5, RS-61443 and subtherapeutic cyclosporine. Group 3 animals achieved a median survival of 136 days, while the median survivals of groups 1, 2, 4, and 5 were < or = 10 days (P < .001). Twenty deaths in groups 1 through 5 were secondary to allograft rejection, two were due to infection, and two were unexplained. Four animals in group 3 were sacrificed, one at 83 days due to diarrhea and weight loss and three at the termination of the study. The median survival of five dogs undergoing total orthotopic transplantation (group 6) was 27.0 days and was significantly longer than groups 1, 4, and 5 (P < .01). No dog in this group had intestinal rejection--however, four were sacrificed due to weight loss and one died of malnutrition. The combination of RS-61443 and cyclosporine significantly prolonged intestinal allograft survival in both the heterotopic and orthotopic transplant models. Clinically, this combination may be promising for both combined liver-intestinal and isolated intestinal transplantation. PMID- 8475539 TI - Prolonging discordant xenograft survival with anticomplement reagents K76COOH and FUT175. AB - The guinea pig heart, when transplanted into the rat heterotopically, is rejected within 30 min via activation of the alternative complement pathway. Natural antibody does not contribute to rejection. This xenotransplantation model was used to assess the effect of anti-complement reagents on discordant xenograft survival. In vivo administration of K76COOH (K76) to rats induced only slight suppression of factors B and D and a marked decrease of C3, leading to the depression of ACH50 (reflecting the potency of the alternative pathway). On the other hand, FUT175 (FUT) reduced C3 activity by about 80% and inhibited factor B activity nearly 100% < 1 hr after the administration, but inhibited factor D activity only marginally. FUT abrogated ACH50 for > 6 hr. Of note, the xenograft beating time was prolonged approximately 3 times by FUT but not by K76, suggesting that direct inhibition of plasma serine protease factor B results in the complete suppression of ACH50 and graft survival. The administration of both K76 and FUT resulted in the longest graft survival, but the effects of these reagents were abolished by additional antigraft antibody. Anticomplement reagents that block factor B and C3 are therefore effective for prolongation of discordant xenograft survival when the graft rejection is associated with the complement alternative pathway. PMID- 8475540 TI - Treatment of severe diabetes mellitus for more than one year using a vascularized hybrid artificial pancreas. AB - We report the successful application of a hybrid artificial pancreas device for the treatment of severe diabetes mellitus induced by total pancreatectomy in two dogs. Control of the blood sugar was achieved for more than 1 year in these two animals without any immunosuppressive therapy. Although exogenous insulin was required therapy. Although exogenous insulin was required during the latter part of the study period, removal of the devices resulted in a rapid increase in the fasting blood sugar levels and the exogenous insulin requirements (P < 0.001 versus weeks 1-52 in both dogs). Metabolic studies, postexplant in vitro studies, and histologic analyses confirmed islet cell survival and insulin production by the devices. This hybrid artificial pancreas has a clear clinical potential for islet cell transplantation without immunosuppression. PMID- 8475541 TI - Islet allograft, islet xenograft, and skin allograft survival in CD8+ T lymphocyte-deficient mice. AB - Despite extensive study, the immunologic mechanisms mediating allograft rejection have not been completely defined. In the current study, we evaluated the T cell subsets important in islet allograft, skin allograft, and islet xenograft rejection using a genetically engineered line of mice deficient in beta 2 microglobulin expression. Because these mice lack cell surface MHC class I expression, they are deficient in T cells of the CD8 subset (class I-restricted cytotoxic T cells). Pancreatic islet allografts transplanted to CD8+ T cell deficient recipients showed prolonged survival compared with controls. No prolongation was observed in the survival of pancreatic islet xenografts or in the survival of skin allografts transplanted to the CD8+ T cell--deficient hosts. We conclude that CD8+ T cells play a prominent role in islet allograft, but not islet xenograft or skin allograft, rejection in mice. PMID- 8475542 TI - Nonhuman primate responses to murine and humanized OKT4A. AB - A nonhuman primate antimurine response (MAMA) has been observed in 17 cynomolgus renal allograft recipients of murine OKT 4A. Neither cyclosporine, nor total lymphoid irradiation, nor donor bone marrow preparation inhibited this antixenogeneic response. In an attempt to alter the antimurine basis of the response, a humanized chimeric OKT4A (IgG4) containing the entire variable portion of the murine OKT4A and a humanized CDR grafted OKT4A mAb sharing only the Complementarity Determining Region from the murine OKT4A, were administered to 8 cynomolgus allograft recipients. MAMA was detected in each recipient. In contrast to sera from recipients of murine OKT4A, sera from recipients of humanized OKT4A displayed no reactivity to other murine mAbs. MAMA specificity did not assay constant (C) region differences between the murine and humanized mAb; however, C region homology in humans should preclude a human antimouse antibody (HAMA) to the Fc portion of a humanized mAb. Furthermore, cynomolgus recipient serum levels of the humanized OKT4A mAb were maintained (> 1 microgram/ml) for a longer period than following treatment with murine OKT4A (murine < 12 days versus between 12 and 24 days for the humanized). If the HAMA response to humanized mAb in future clinical trials, were to be predictably anti idiotypic, then the opportunity for treatment with sequential mAbs of differing idiotypes would be retained. Moreover, these current studies also suggest that humanized construction may influence the duration of therapeutic mAb levels. Thus, anti-idiotypic reactivity may not be as consequential to the clinical administration of humanized mAb to allograft recipients. PMID- 8475543 TI - Livers from fasted rats acquire resistance to warm and cold ischemia injury. AB - Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold ischemia. In fact, the livers appeared to be better able to tolerate ischemia when obtained from fasted rats. Thus donor nutritional status may be an important factor for outcome of liver transplantation. Livers from fasted donors may be capable of tolerating long-term preservation better than livers from fed donors. PMID- 8475544 TI - Assessment of purine metabolism in human renal transplantation. AB - Cortical levels of nucleotides and their degradation products from 42 transplanted human kidneys have been studied. Biopsies were performed during renal harvesting just before cooling, at the end of cold storage, and following reinstallment of renal blood circulation. ATP levels fell, and AMP and degradation products (inosine monophosphate [IMP], inosine, adenosine, and hypoxanthine) increased during cold storage and returned to near-normal values 30 min after recirculation. The major degradation product found was hypoxanthine, indicating very poor xanthine oxidase activity in human kidneys. The sum of adenine nucleotides (ATP+ADP+AMP) did not significantly decrease after cold storage, but adenylate energy charge (ATP+1/2ADP/ATP+ADP+AMP) was reduced to half, being recovered in implanted kidneys. The sum of adenine nucleotides was significantly reduced after implantation. The rate of acute tubular necrosis was higher in kidneys preserved for more than 30 hr. Kidneys with acute tubular necrosis had significantly lower levels of the total pool of adenine nucleotides at reperfusion, but there was no correlation between incidence of acute tubular necrosis and ATP or other metabolite levels in the kidneys before or during cold preservation. The success of human kidney transplantation does not seem to depend only on the pool of residual nucleotides at the end of cold storage but on other factors that determine the ability of the cell to recover a normal energy state after reperfusion. PMID- 8475545 TI - A rat fatty liver transplant model. AB - A rat model of fatty liver transplantation has been developed to study primary nonfunction in fatty liver grafts. ACI rats were fed with a diet deficient in choline and methionine for 7, 14, 28, and 42 days. Fat content in the pretransplant livers was examined by gas chromatography and histology. The main constituent of the fatty droplets was determined to be triglyceride. The triglyceride concentration reached a maximum by day 14 and remained constant for an additional 28 days. Histology revealed an absence of necrosis in 14- and 28 day fatty livers but scattered hepatocytic necrosis and inflammation in 42-day fatty livers. After being given cold (UW stored, 4 degrees C) or warm (37 degrees C) ischemia, the fatty liver was orthotopically transplanted into normal ACI rats. The one-week survival of fatty liver grafts after 6, 12, 18, and 24 hr cold preservation was 5/5, 5/6, 3/8, 0/6 for 14-day fatty liver and 5/5, 4/6, 0/8, 0/6 for 42-day fatty livers. The survival of normal liver grafts was 5/5, 6/6, 5/9, 2/8, respectively. Increased survival rate was correlated with the absence of hepatocytic necrosis. The survival after 15 and 30 min warm ischemia prior to transplant was 5/5, 2/6 for normal liver grafts and 4/7, 0/6 for 28-day fatty liver graft, respectively. Fatty livers were less resistant to damage induced by cold or warm ischemia. PMID- 8475546 TI - The effect of immunosuppression on pre-existing cancers. AB - This study of 939 pre-existing malignancies that occurred in 913 renal transplant recipients showed that in 823 patients the tumors were treated prior to or at transplantation, in 78 after transplantation, at an unspecified time in 20, while 18 received no treatment. Of patients treated pretransplantation 185 (22%) developed recurrences posttransplantation. Low recurrence rates (0-10%) occurred with incidentally discovered renal tumors; lymphomas; and testicular, uterine cervical, and thyroid carcinomas. Intermediate recurrence rates (11-25%) occurred with carcinomas of the uterine body; Wilms' tumors; and carcinomas of the colon, prostate, and breast. High recurrence rates (> or = 26%) occurred with carcinomas of the bladder, sarcomas, malignant melanomas, symptomatic renal carcinomas, nonmelanomatous skin cancers, and myelomas. Overall 53% of 185 recurrences occurred in patients treated 0-24 months pretransplantation, 34% in patients treated 25-60 months pretransplantation, and 13% in patients treated > 60 months pretransplantation. Of 78 patients whose cancers were first treated after transplantation, 27% developed recurrences. However, 63% did not do so in follow ups averaging 53 months. A two-year waiting period between treatment of cancer and transplantation is justified for most neoplasms except for incidentally discovered renal carcinomas, in situ carcinomas, and possibly focal neoplasms (a small single focus), low-grade bladder cancers, and basal cell skin cancers. In these cases no waiting period is necessary. On the other hand, a waiting period > 2 years is necessary for most malignant melanomas, breast carcinomas, and colorectal carcinomas. Conflicting data are presented as to whether immunosuppression affects growth of existing tumor cells but most of the evidence suggests acceleration of neoplastic growth. PMID- 8475547 TI - A randomized, prospective, double-blinded trial of cyclosporine vs. OG37-325 in cadaveric renal transplantation--a preliminary report. AB - The efficacy of cyclosporine is documented, but it has side effects that are troublesome. Another compound, OG37-325, has been identified that appears to have similar efficacy, but less nephrotoxicity. This study was designed to address the benefits and toxicities of cyclosporine and OG37-325 in a prospective, randomized, double-blinded trial in cadaveric renal transplant recipients. The preliminary results demonstrate similar outcomes in terms of patient and graft survival, but suggest less nephrotoxicity in the OG37-325-treated patients. Longer follow-up will delineate the utility of OG37-325 in solid-organ transplantation. PMID- 8475548 TI - Risk factors for chronic rejection in renal allograft recipients. AB - Chronic rejection is a major barrier to long-term renal allograft survival. Cyclosporine, though effective at reducing graft loss to acute rejection, has had little impact on the incidence of chronic rejection. Between June 2, 1986 and January 22, 1991, 587 kidney-alone transplants (566 patients) were performed, and had been entered into our renal transplant database and had at least 1 year of follow-up: 103 with biopsy-proven chronic rejection (37 living-related donor, 66 cadaver) and 484 without chronic rejection (236 LRD 248 CAD). The 5-year patient survival was 84% for recipients with biopsy-proven chronic rejection vs. 89% without (P = .08). The 5-year graft survival was 31% for recipients with biopsy proven chronic rejection vs. 81% without (P < .0001). Using multivariate analysis, we determined the impact on the incidence of chronic rejection of these variables: transplant number, age at transplant (< 18 years, 18 to 50 years, > 50 years), gender, human leukocyte antigen matching, peak and transplant panel reactive antibody, acute rejection episodes, infections (including cytomegalovirus, viral, and bacterial), donor age, and CsA dosage at 1 year (< 5 mg/kg vs. > or = 5 mg/kg). Logistic regression models were fit to the data using a forward stepwise selection procedure. In this analysis, risk factors included an acute rejection episode (P < .001), CsA dosage < 5 mg/kg/day at 1 year (P = .007), infection (P = .023), female gender (P = .042), and retransplant (P = .103). Individual analyses were done for CAD and LRD recipients. For both groups, important variables were acute rejection, infection, CsA dosage at 1 year, and age at transplant. In conclusion, acute rejection, CsA dosage < 5 mg/kg/day at 1 year, and infection are the major risk factors for the development of chronic rejection, suggesting that chronic rejection may be the result of inadequate immunosuppression (acute rejection episodes and low CsA dosage) or the production of inflammatory cytokines (infections). PMID- 8475549 TI - Half-life and risk factors for kidney transplant outcome--importance of death with function. AB - Transplant center outcome is being increasingly scrutinized, so it is critical to have a consistent approach to data analysis. Standard practice has been to include death with function as a graft loss. But doing so may obscure other important risk factors and make it difficult to compare centers. To document this data analysis problem, we studied half-life and risk factors for long-term graft survival in 2230 kidney transplant recipients who had > or = 1 year of function. Four separate Cox regression analyses were done, differing in how death with function is considered: death with function considered a graft loss (analysis 1); all deaths censored (analysis 2); definitively non-transplant-related deaths censored, i.e., deaths from infection, malignancy, or cardiac problems analyzed as a graft loss (analysis 3); and definitively non-transplant-related as well as cardiac deaths censored (analysis 4). For each analysis, variables included immunosuppressive protocol, age at transplant, donor source, diabetes, gender, transplant number (primary vs. retransplant), and HLA ABDR mismatches (0 vs. > or = 1 mismatch). There were important differences in risk factors, depending on how death with function is considered. For example, when all deaths are considered a graft loss, age > 50, cadaver donor source, diabetes, retransplantation, and > 0 antigen mismatch were found to be risk factors for long-term graft survival. However, when all deaths are censored, age > 50, cadaver donor source, retransplantation, and diabetes were no longer risk factors. In fact, age > 50 was associated with significantly better graft survival when all deaths are censored (analysis 2), suggesting that the increased graft loss seen in these patients is nonimmunologic. Similarly, t1/2 is markedly different for different patient subgroups depending on how death with function is considered. For example, nondiabetic living donor (non-HLA-identical) recipients > 50 have a t1/2 of 9 +/- 1 years when death with function is considered a graft loss; for the same group, t1/2 is 62 +/- 28 years when death with function is considered. For diabetic patients < or = 50, when death with function is considered a graft loss, t1/2 is 9 +/- 0.9 years for living donor recipients and 7 +/- 0.7 years for cadaver donor recipients. For the same patients, when death with function is censored, t1/2 is 27 +/- 4 years for living donor recipients and 24 +/- 4 years for cadaver donor recipients. Our analysis suggests that death with function needs to be considered in analyzing kidney transplant outcomes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475550 TI - Frequency of kidney rejection in diabetic patients undergoing simultaneous kidney and pancreatic islet cell transplantation. AB - An increased frequency of kidney rejection has been reported in diabetic patients who have simultaneous pancreas and kidney transplantation compared with patients who have a kidney transplant alone. Kidney graft outcome is similar in the two groups. The mechanism for increased kidney graft rejection with a simultaneous pancreas graft is not clear. It is ascribed to the immunogenicity of the exocrine pancreas that initiates migration of activated cells from the peripheral blood that are entrapped in the kidney. Since the volume of the transplanted tissue is less in islet transplantation (usually < 2 ml) than in pancreas transplantation, one might not expect an increased frequency of kidney rejection in islet cell recipients. We looked at biopsy-proven kidney rejection episodes in patients who had combined kidney and islet transplants and compared this with the frequency of rejection in diabetic and nondiabetic patients who underwent a kidney transplant alone under the same immunosuppression. Diabetic patients who had kidney islet transplants (n = 9) had a higher frequency of rejection (100%) compared with diabetic patients (n = 107, 55.1%) and nondiabetic patients (n = 327, 65%) who had a kidney transplant alone. The 1-year graft and patient survival rates were not different among the groups. Although the number of patients is small, it would appear that transplantation of a low volume of islet cells with high purity can lead to an increased frequency of kidney rejection. This is unlikely to be explained solely on the basis of fewer antigen matches in these recipients but may reflect the inherent immunogenicity of the purified islet preparations. Alternatively, there may be an effect of their direct infusion into the portal vein. PMID- 8475551 TI - Tumor necrosis factor alpha in human kidney transplant rejection--analysis by in situ hybridization. AB - Macrophagic infiltration and necrosis of rejected kidney transplants represent two pejorative patterns. It has been assumed that the macrophagic toxicity is mediated partly by secretion of tumor necrosis factor alpha. On the other hand, TNF is also involved in many inflammatory and immunological phenomena. We thus evaluated the expression of TNF mRNA by in situ hybridization in 6 rejected kidney transplants using a radiolabeled TNF-c DNA probe. Then the synthesis of TNF alpha protein was studied by immunohistochemistry using an anti-TNF alpha antibody. In severely rejected kidney grafts, TNF mRNA is expressed in some monomorphic infiltrating cells, mostly located in the deepest part of the cortex and around the tubes. These cells do not bind other probes, such as dopa decarboxylase DNA or preproenkephalin RNA. They are also recognized by a monoclonal antibody directed against TNF alpha. What is more, this antibody binds with some glomerular endothelial and tubular epithelial cells that do not express TNF mRNA. These cells are likely target cells for TNF. In the normal kidney, there are no cells expressing TNF-alpha mRNA. PMID- 8475552 TI - Renal transplantation following immunoadsorption in highly sensitized recipients. AB - Five highly sensitized patients, with panel reactivity greater than 80% for 1.75 5 years, were treated by extracorporeal staphylococcal protein-A immunoadsorption, prednisolone, and cyclophosphamide. The five patients underwent treatment of 18-40 (mean 31) liters of plasma, respectively in 4-7 (mean 5.6) sessions. This reduced the titer of cytotoxic antibodies to sensitizing antigens to < 1/8 in all cases and abolished reactivity to crossreacting antigens. Two patients required retreatment following resynthesis of cytotoxic antibodies. All five patients have been transplanted, and four of these now have stable serum creatinines of 168 mumol/L at 34 months, 208 mumol/L at 29 months, 96 mumol/L at 5 months, and 125 mumol/L at 3 months posttransplantation. One patient had primary graft dysfunction due to acute tubular necrosis; the kidney was removed after eight weeks and showed cortical necrosis without evidence of acute rejection. PMID- 8475553 TI - Steroid withdrawal from long-term immunosuppression in liver allograft recipients. AB - Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication. PMID- 8475554 TI - Complement activation during liver transplantation. AB - Twelve patients with end-stage liver disease undergoing liver transplantation were studied regarding complement activation and formation of anaphylatoxins (C3a and C5a) and terminal C5b-9 complement complexes (TCC) after reperfusion of the grafted liver. Blood samples for complement variables (C1INH, C3, C4, C5, C3a, C5a, and TCC) were drawn preoperatively, before the anhepatic phase, 1 min before, and 2, 15, and 60 min after the start of reperfusion of the grafted liver. Activation of complement was observed during the operation. The C1INH, C3, C4, and C5 plasma concentrations decreased during the entire operation while the anaphylatoxin C3a and the terminal C5b-9 complement complex increased after the reperfusion of the grafted liver. Activation of complement with the formation of biologically active substances like anaphylatoxins and terminal C5b-9 complement complexes may be one explanation for circulatory complications often seen in patients undergoing orthotopic liver transplantation. PMID- 8475555 TI - Hepatic retransplantation in New England--a regional experience and survival model. AB - Hepatic retransplantation (reTx) offers the only alternative to death for patients who have failed primary hepatic transplantation (PTx). Assuming a finite number of donor organs, reTx also denies the chance of survival for some patients awaiting PTx. The impact of reTx on overall survival (i.e., the survival of all candidates for transplantation) must therefore be clarified. Between 1983 and 1991, 651 patients from the New England Organ Bank underwent liver transplantation, and 73 reTx were performed in 71 patients (11% reTx rate). The 1 year actuarial survival for reTx (48%) was significantly less than for PTx (70%, P < 0.05). This survival varied, dependent on the interval of time following PTx in which the reTx was performed (0-3 days, 57% survival; 4-30 days, 24%; 30-365 days, 54%; and > 365 days, 83%). Patients on the regional waiting list had an 18% mortality rate while awaiting transplantation. These results were incorporated into a mathematical model describing survival as a function of reTx rate, assuming a limited supply of donor livers. ReTx improves the 1-year survival rate for patients undergoing PTx but decreases overall survival (survival of all candidates) for liver transplantation. In the current era of persistently insufficient donor numbers, strategies based on minimizing the use of reTx, especially in the case of patients in whom chances of success are minimal, will result in the best overall rate of patient survival. PMID- 8475556 TI - Risk factors for primary dysfunction after liver transplantation--a multivariate analysis. AB - In a retrospective analysis on 323 orthotopic liver transplant procedures performed between July 1984 and October 1991 the incidence of two forms of primary dysfunction (PDF) of the liver: primary nonfunction (PNF), and initial poor function (IPF) were studied. The incidence of PDF was 22% (73/323) with 6% PNF (20/323) and 16% IPF (53/323), while 78% (250/323) had immediate function (IF). Occurrence of both IPF and PNF resulted in a higher graft failure rate (P < 0.001), retransplantation rate (P < 0.001), and patient mortality (P < 0.003) within the first three months after OLTx. Univariate analyses of donor and recipient factors and their influence on PDF demonstrated that longer donor hospitalization (> 3 days), older donor age (> 49 years), extended preservation times (> 18 hr), and fatty changes in the donor liver biopsy, as well as reduced size livers, younger recipient age, and renal insufficiency prior to OLTx, significantly affected the incidence of IPF and PNF. Multivariate analysis of potential risk factors showed that reduced-size liver (P = 0.0001), fatty changes on donor liver biopsy (P = 0.001), older donor age (P = 0.009), retransplantation (P = 0.01), renal insufficiency (P = 0.02), and prolonged cold ischemia times (P = 0.02) were independently associated with a higher incidence of IPF and PNF. No statistical correlation was found between PDF and etiology of ESLD, nutritional status of the recipient, UNOS status, and Child-Pugh classification in this study. We conclude that PNF and IPF are both separate clinical entities that have a significant effect on outcome after OLTx. Routine donor liver biopsies are recommended to decrease the rate of IPF and PNF. The combination of risk factors shown to be significant for PDF should be avoided--and, if that is not possible, the only variable that can be controlled, the preservation time, should be kept as short as possible. PMID- 8475557 TI - Probable antibody-mediated failure of two sequential ABO-compatible hepatic allografts in a single recipient. AB - Two sequential ABO-compatible orthotopic liver allografts failed, despite excellent initial posttransplant function, in a patient with preformed donor specific alloantibodies. There was no evidence of cell-mediated rejection. Retrospective crossmatching of recipient serum, obtained immediately prior to the first transplant, revealed the presence of lymphocytotoxic antibodies directed against donor class I HLA B17, at a titer of greater than 1:32,768. Similarly, lymphocytotoxic antibodies directed against the second donor's class I HLA A2 phenotype were detected on retrospective crossmatching utilizing both the three wash Amos technique (TWA-CDC), and the anti-human immunoglobulin augmented technique (AHG-CDC), at a titer of greater than 1:32,768. Anti-class I specific alloantibodies were eluted from both failed liver grafts at titers of 1:256. The hepatic necrosis in zones 3 and 2 that were observed on histologic examination, and the profound refractory consumptive thrombocytopenia subsequent to each transplant may have been the result of antibody-mediated rejection by preformed lymphocytotoxic antibodies. Despite the liver's remarkable capacity to withstand antibody-mediated injury, primary humoral rejection following ABO compatible liver transplantation may occur if extremely high titers of performed allospecific lymphocytotoxic antibodies are present. PMID- 8475558 TI - Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation. AB - Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization. PMID- 8475559 TI - Right phrenic nerve injury in orthotopic liver transplantation. AB - Right hemidiaphragm paralysis has been previously documented in patients after orthotopic liver transplantation (OLT) and it may contribute to the development of postoperative pulmonary problems. It has been postulated that a crush injury to the right phrenic nerve during OLT is the cause of dysfunction of the right hemidiaphragm. To assess the incidence and effect of right phrenic nerve injury after OLT, we prospectively studied 48 adult liver recipients. Twelve patients who underwent liver resection (LR), in whom the suprahepatic vena cava was not clamped, were used as a comparison group. Diaphragm excursion by ultrasound and pulmonary function were performed preoperatively and postoperatively; transcutaneous phrenic nerve conduction studies were performed postoperatively. Right phrenic nerve injury and hemidiaphragm paralysis occurred in 79% and 38% of the liver recipients but not after LR. Conduction along the right phrenic nerve was absent in 53% and reduced in another 26%. Left phrenic nerve conduction and left hemidiaphragm excursion were normal in both liver recipients and the patients who had LR. Liver recipients with no conduction in the right phrenic nerve had a significantly greater decrease in vital capacity in the supine position (29 +/- 9.8%) compared with those with some conduction (14 +/- 6.9%, P < 0.001). However, neither the time on the ventilator nor the hospital stay was significantly different in the latter two groups. Complete recovery of phrenic nerve conduction and diaphragm function took until nine months in some patients. Right phrenic nerve injury is common after OLT and it is the cause of right hemidiaphragm dysfunction. PMID- 8475560 TI - Hepatic lidocaine metabolism and complications of cirrhosis. Implications for assessing patient priority for hepatic transplantation. AB - The number of patients awaiting hepatic transplantation continues to exceed organ donation. As a result, many liver transplant candidates will develop life threatening complications of their liver disease and not survive the pretransplant waiting period. Recent studies have demonstrated that hepatic lidocaine metabolism into monoethylglycinexylidide (MEG-X) can predict pretransplant survival. The present study was performed to determine if MEG-X could also predict pretransplant complications and thereby be useful in stratifying persons being evaluated for hepatic transplantation. A total of 57 patients with biopsy-proven cirrhosis underwent MEG-X testing. Of 57 patients, 30 (53%) developed life-threatening complications of their liver disease--i.e., variceal bleeding, grade II hepatic encephalopathy or worse, and spontaneous bacterial peritonitis. MEG-X values were greater in persons without complications of liver disease than in persons with complications (25.7 +/- 2.9 versus 14.7 +/- 1.4 ng/ml, respectively). No patients with MEG-X greater than 30 ng/ml developed a major complication. No significant difference in any of the standard liver function tests existed between persons who developed complications and patients who did not. In this group of 57 patients, 4 (7%) died from complications of cirrhosis. Mean MEG-X for patients who died (5.5 +/- 1.6 ng/ml) was significantly less (P < 0.05) than observed for other patient groups. All patients who died had MEG-X values below 10 ng/ml. This suggests that MEG-X testing could be an extremely useful test in the evaluation of patients for hepatic transplantation by identifying persons at increased risk for developing complications of chronic liver disease. PMID- 8475561 TI - Prolongation of cardiac xenograft survival by depletion of complement. AB - Complement (C) activation is thought to be critical for the hyperacute rejection of xenografts. We investigated the role of C in the rejection of discordant cardiac xenografts by studying outcome in recipients depleted of C, using a highly purified form of cobra venom factor (CVF) in both a small (guinea pig [GP] to-rat) and large (pig-to-baboon) animal model. A single dose of 30 or 60 units CVF given i.v. to rats completely abrogated hemolytic C activity for up to 72 hr. The lack of hemolytic C activity correlated with nearly undetectable serum levels of C3. Doses of 30 U/kg daily or 60 U/kg every other day over a 7-day period sustained C depletion without morbidity or mortality. Rats receiving GP cardiac xenografts during CVF therapy had significantly prolonged xenograft survival (88 +/- 10 hr in CVF-treated rats vs. 18.6 +/- 7.2 min in control rats, P < 0.001). Rats that rejected GP xenografts at 4 days posttransplant had higher levels of anti-GP antibodies than control rats, without hemolytic C activity at rejection. This rise in xenoreactive Ig reflected an increase in circulating IgG and IgM against GP antigens recognized before transplantation. Histologic analysis of GP cardiac xenografts taken from CVF-treated rats revealed leukocyte and monocyte margination along blood vessels, beginning at 12 hr posttransplant. Progressive cell infiltration, interstitial hemorrhage, and necrosis were observed over the next 72 hr. Rejected GP xenografts showed diffuse deposition of IgM and fibrin within blood vessels but no evidence of C3 deposition. A nonspecific pattern of IgG deposition was noted. CVF was tested in baboons. Complete C depletion was achieved with a dose of 60 U/kg, and was not associated with any morbidity or mortality. Xenotransplantation of a pig heart was performed in one baboon receiving CVF, 60 U/kg/day, for 2 consecutive days. Xenograft survival was prolonged to 68 hr, compared with 90 +/- 30 min in control baboons. Lack of hemolytic activity was noted during engraftment and at rejection. Histology showed evidence of vascular rejection. Immunopathology showed diffuse deposition of IgM, fibrin, and C4, and absence of C3 or membrane attack complex. We conclude that highly purified CVF can achieve marked C depletion with minimal morbidity and no associated fatalities. CVF alone can significantly prolong discordant cardiac xenograft survival. In the GP-to-rat model, the improvement in graft survival achieved with CVF was better than with conventional immunosuppression or isolated acute antibody depletion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475562 TI - Prolonged survival of rat orthotopic liver allografts after intrathymic inoculation of donor-strain cells. AB - Permanent donor-specific tolerance to tissue or organ allografts can be readily achieved without immunosuppression by administration of donor lymphohematopoietic cells to neonatal rodents. In adult recipients, however, induction of transplantation tolerance by this strategy generally requires intensive cytoablative conditioning of the recipient. We have now demonstrated that intrathymic inoculation of donor bone marrow or hepatic cells in conjunction with a single dose of antilymphocyte serum is effective in prolonging survival of DA rat orthotopic liver allografts in LEW strain recipients, which ordinarily rapidly reject such transplants. The unresponsive state achieved is donor specific, as evidenced by the failure of intrathymic inocula of third-party WF cells to promote survival of LEW recipients of orthotopic DA liver allografts. Moreover, intravenous administration of the donor cells fails to extend liver allograft survival, demonstrating that the inoculum must be present in the thymus to promote unresponsiveness. Established DA liver allografts induced a state of systemic tolerance in LEW hosts, allowing their subsequent acceptance of donor strain skin allografts. We hypothesize that the unresponsive state achieved by intrathymic inoculation of donor cells may result from the deletion or functional inactivation of alloreactive clones in a thymus bearing donor alloantigens. In this regard, cells of the macrophage/dendritic lineage (descendants of the bone marrow inoculum or hepatic Kupffer cells) may play a critical role by promoting thymic microchimerism and exerting modulatory effect on T cell development. PMID- 8475564 TI - Do donor cells function as veto cells in the induction and maintenance of tolerance across an MHC disparity in mixed lymphoid radiation chimeras? AB - Mixed lymphoid chimeras can be established across H-2b-->H-2d by injection of C57BL/6J (B-6) donor bone marrow cells into BALB/c hosts conditioned by sublethal irradiation, 235 cGy x3. These chimeras are specifically tolerant to both donor and host alloantigens. Tolerance cannot be broken even by injection of 4 x 10(8) normal BALB/c spleen cells (SC), suggesting a suppressor mechanism. In contrast to conventional suppression, however, in which suppressors are syngeneic to the cells they suppress, tolerance can be transferred only by cells of the allogeneic donor allotype (1,2). Thy 1+ cell depletion eliminates the capacity of the donor population to transfer tolerance and markedly reduces the capacity of B-6 BMC to induce tolerance (3). In the present studies spleen cells from tolerant chimeras (CSC), when coinjected in a 1:1 ratio, reduced the high GVHD mortality induced in irradiated H-2d/b F1 hybrids by injection of 2 x 10(7) normal BALB/c SC alone (P < .01). When coinjected at a 5:1 ratio CSC eliminated the GVHD mortality and weight loss induced by 5 x 10(6) BALB/c SC (P < .01). Depletion of B-6 cells from CSC removed their capacity to inhibit the GVHD induced by normal BALB/c SC. In contrast to conventional suppression, which requires the continued presence of suppressor cells, the BALB/c cells isolated from CSC, although unable to inhibit the GVHD of normal BALB/c SC, remained nonreactive against the H-2b allotype for a prolonged period following depletion of the B-6 cells. This prolonged response reduction dependent upon some interaction with allogeneic donor cells--which, in turn, are specifically nonreactive to host antigens--is compatible with a veto mechanism. PMID- 8475563 TI - Induction of donor-specific tolerance to cardiac but not skin or renal allografts by intrathymic injection of splenocyte alloantigen. AB - We have recently found that donor-specific tolerance to a cardiac allograft can be achieved after the intrathymic (i.t.) injection of donor splenocytes and a single intraperitoneal injection of rabbit antirat lymphocyte serum. The present study evaluated whether the tolerance induced by splenocytes injected i.t. could also prevent the rejection of kidney and skin allografts. Male Buffalo (RT1b) rats were given 25 x 10(6) fully MHC-mismatched unfractionated Lewis (RT1l) splenocytes by i.t. injection plus 1 ml of ALS i.p. and 21 days later underwent a Lewis heterotopic cardiac, orthotopic renal, or skin transplant. Lewis i.t. injection induced a donor-specific tolerance with indefinite cardiac allograft survival (> 153.1 days) in 88% of the recipients without the need for further immunosuppression, while renal and skin allograft survival was prolonged (kidney 14.8 days vs. control 7.8 days; skin 11.6 days vs. control 9.2 days) but were still rejected. Buffalo recipients with a long-surviving Lewis cardiac allograft after Lewis i.t. injection were still able to reject a third-party heterotopic ACI (RT1a) cardiac allograft in normal time (7.0 days), but did not reject a second Lewis cardiac allograft (> 100.0 days). In contrast, however, Buffalo recipients with long-surviving Lewis cardiac allografts did reject a Lewis skin allograft in normal time (10.0 days) and a Lewis renal allograft in a prolonged manner (17.6 days) without causing the rejection of the Lewis cardiac allografts. These data support the important role tissue-specific non-MHC antigens may play in the rejection of kidney and skin allografts. PMID- 8475565 TI - The mechanism of unresponsiveness to allografts induced by rapamycin and rapamycin/cyclosporine treatment in rats. AB - The mechanisms by which rapamycin (RAPA) and/or cyclosporine induce unresponsiveness to allografts were investigated in a rat model. Buffalo (BUF, RT 1b) heart allografts were rejected by Wistar-Furth (WFu, RT-1u) recipients at a mean survival time (MST) of 6.5 +/- 0.5 days. A 14-day course of RAPA (0.8 mg/kg) delivered intravenously by an osmotic pump prolonged BUF allograft survival to 76.1 +/- 23.4 days (P < 0.001). Adoptive transfer of 30-50 x 10(6) spleen and lymph node T cells that had been isolated on day 40 postgrafting from CsA- or RAPA/CsA-treated hosts into lightly irradiated (6 Gray) secondary WFu recipients prolonged BUF graft survival from 9.8 +/- 1.2 to 29.2 +/- 11.0 (P < 0.01) and 58.2 +/- 38.9 days (P < 0.004), respectively. T cells transferred from animals treated with RAPA alone failed to prolong graft survival. In contrast, sera isolated on day 40 postgrafting from WFu primary hosts treated with RAPA alone or with the RAPA/CsA combination, but not with CsA alone, extended the survival of BUF hearts: 3 ml serum from RAPA-treated hosts prolonged BUF heart survival to 76.6 +/- 31.3 days (P < 0.002) and from RAPA/CsA-treated hosts to 47.1 +/- 12.8 days (P < 0.001). The effect of serum was immunologically specific: it did not prolong the survival of third-party outbred Sprague Dawley heart allografts. Although the IgM fraction (0.2 mg) purified from the serum of RAPA-treated recipients was ineffective (10.6 +/- 0.8 days; NS), an equal amount of the IgG fraction significantly (P < 0.002) prolonged BUF heart allograft survival to 26 days (n = 4). Thus, hosts treated with RAPA or a RAPA/CsA combination develop IgG antibodies that mediate the unresponsive state toward allogeneic heart allografts. PMID- 8475566 TI - The synergistic interactions in vitro and in vivo of brequinar sodium with cyclosporine or rapamycin alone and in triple combination. AB - The rigorous median-effect analysis was used to assess the interactions between cyclosporine and drugs that inhibit nucleotide synthesis pathways. Using in vitro proliferation assays wherein human lymphocytes were triggered by phytohemagglutin, anti-CD3 monoclonal antibody, or mixed lymphocyte reactions, CsA was shown to display additive interactions with 6-mercaptopurine (6-MP), mizorbine (MZB), and mycophenolic acid (MPA), and a synergistic interaction with brequinar (BQR). In the in vitro assays, BQR contributed a further synergistic effect to the double-drug combination CsA/rapamycin (RAPA). Of the four inhibitors of nucleotide synthesis pathways, only BQR noncompetitively inhibited IL-2-stimulated proliferation of the CTLL-2 cell line. Using the in vivo assay of heterotopic Buffalo (BUF, RT-1b) cardiac allografts in Wistar-Furth (WFu, RT-1u) hosts, oral administration of BQR displayed about 100% bioavailability--which, like the bolus intravenous (i.v.) mode, was eight-fold more effective than continuous i.v. infusions. Furthermore median-effect analysis of serial amounts of orally administered BQR demonstrated that it contributes synergistically to the immunosuppressive effects of intravenously delivered CsA/RAPA (0.5/0.01 mg/kg/day). The degree of synergism was proportionate to the extent of the immunosuppression. These findings document the potency of the CsA/RAPA/BQR triple drug combination and suggest that the synergistic effects may permit dose reductions of each component, thereby mitigating toxicities resulting from the large amounts of individual agents necessary to achieve allo-unresponsiveness. PMID- 8475567 TI - Evidence for a nonclassical pathway of graft rejection involving interleukin 5 and eosinophils. AB - The role of IL-5 and eosinophils in allograft rejection was studied in human liver allograft recipients. Liver allograft biopsies were analyzed for intragraft IL-5 gene expression, and the percentages of eosinophils and plasma cells within the portal infiltrate as well as peripheral eosinophil levels were determined. The majority of allografts with evidence of rejection had concomitant IL-5 mRNA and eosinophilia, while no resolving or nonrejecting allografts had simultaneous IL-5 mRNA and eosinophilia. In fact, rejecting liver allografts that contain IL-5 mRNA and eosinophils also contain infiltrating cells that produce the cytotoxic mediator major basic protein. In contrast, intragraft plasma cell and peripheral eosinophil levels did not correlate with the histopathologic status of the allograft. Cyclosporine and FK506 had similar effects on the frequency of IL-5 gene expression in rejecting and nonrejecting allografts. However, OKT3 appeared to profoundly modulate IL-5 gene expression, since 0 of 11 biopsies obtained during OKT3 treatment for rejection contained IL-5 transcripts. These observations raise the possibility of a cellular pathway of liver allograft rejection mediated by IL-5-activated eosinophils. PMID- 8475568 TI - Alloantigen-dependent endothelial phenotype and lymphokine mRNA expression in rejecting murine cardiac allografts. AB - Recent studies suggest that graft microvascular endothelia may play an important role in the regulation of rejection. Alloantigen-dependent changes in microvascular endothelial phenotype may be associated with differences in infiltrate function in allografts vs. isografts, as reflected in alloantigen specific CTL accumulation and cytokine production. To correlate cytokine production with differences in microvascular endothelial phenotype during allograft inflammation, we used PCR to identify cytokine mRNAs isolated from pooled cardiac isografts and allografts on days 1, 3, and 5 after transplantation. Graft microvascular endothelia express an inflamed phenotype associated with wound healing and the repair of tissue damage due to mechanical trauma, ischemia, and/or reperfusion injury--i.e., high levels of ICAM-1 expression and MECA-32 mAb reactivity. By day 1 in both isografts and allografts, mRNAs for the cytokines IL1 alpha, IL6, TNF, LT, and TGF beta are upregulated or induced. By the third day in cardiac allografts, an antigen-dependent endothelial phenotype is expressed, characterized by the presence of cell surface VCAM-1. Concomitantly, mRNAs for the lymphokines IL2 and IFN gamma are detected, followed by IL4 mRNA by day 5. The expression of VCAM-1 by allograft endothelia may influence the inflammatory process, by physically recruiting specific T cell subpopulations into the response and/or by delivering additional signals to the infiltrating cells. Eventually, these and other regulatory events occurring at these early times initiate a process that later results in alloreactive tissue destruction. PMID- 8475569 TI - The human antiporcine cellular repertoire. In vitro studies of acquired and innate cellular responsiveness. AB - Discordant xenogeneic transplantation offers a potentially unlimited source of donor organs from easily bred, nonendangered, physiologically compatible animals, but has been limited by the inevitable occurrence of hyperacute rejection (HAR). The potential existence of cell-mediated discordant graft rejection has remained obscured by HAR, and hence is incompletely understood. To define the cellular elements capable of recognition of and subsequent response against discordant tissue in a clinically applicable species combination, we have studied the in vitro interaction of human peripheral blood lymphocytes against 3 porcine B lymphoblastoid cell lines and 6 primary porcine endothelial cell populations. PBL from all individuals tested (n = 10) proliferated in response to culture for 72 hr in xenogeneic mixed lymphocyte culture (XMLC) with cell lines expressing porcine MHC (SLA) class II antigens, while endothelial cultures lacking SLA class II generally failed to evoke a response. The proliferative response to class II positive cells was attenuated by addition of anti-SLA class II antibody but not by anti-SLA class I antibody. Two endothelial populations expressing class II stimulated an inhibitable proliferative response. The magnitude of the short-term proliferative xenogeneic response was similar to that evoked by fully mismatched allogeneic human B lymphoblastoid stimulators. Additionally, extended XMLC was performed with PBL from 3 individuals. All populations responded with continued proliferation when repeatedly stimulated by porcine cells. This was characterized not only by T cell growth, but by prominent NK cell growth as well. Elucidation of the TCR V beta chain usage patterns by semiquantitative PCR documented selection of TCR transcripts from gene family V beta 2 in each group, complemented by a heterogeneous mixture of other transcripts including V beta 17.1, 20.1, and 6.1, suggesting that direct human TCR binding of porcine cells occurs, and that it is likely to be an individualistic response complemented by a more homogeneous NK response. A 51Cr release assay was utilized to demonstrate that unprimed PBL could also lyse porcine target cells. This cytotoxic response was maintained despite the complete removal of T cells, suggesting that porcine directed NK cell activity is present prior to the maturation of any T cell response. Cytolysis was also demonstrated in serum-free medium and thus was not mediated solely by antibody-dependent cellular cytotoxicity. Chinese hamster ovary cells transfected with the human T cell receptor accessory molecule CD4 were used to study the ability of this molecule to stabilize the interaction between the human TCR and SLA class II.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475570 TI - Use of donor beta 2-microglobulin-deficient transgenic mouse liver cells for isografts, allografts, and xenografts. AB - Donor graft major histocompatibility complex class I antigens are targets for both allogeneic and xenogeneic rejection. Mice homozygous for beta 2 microglobulin gene disruption express reduced amounts of surface MHC class I antigens. Liver cells from such mutant mice were transplanted into isogeneic, allogeneic, and xenogeneic recipients to evaluate the potential of these animals as transplant donors. The survival of allografts of transgenic 129 mouse liver cells in 15 immunocompetent and histoincompatible mouse recipients (BALB/c, D1.C) was only slightly improved 30 days after transplantation relative to normal 129 mouse allografts. These results could be attributable: (1) to host natural killer cell-mediated lysis of donor MHC class I antigen-deficient cells; (2) to donor liver cell MHC class I determinants that are reduced but not eliminated serving as rejection targets; (3) to the plentiful host supply of serum beta 2 microglobulin reconstituting the graft and restoring donor MHC class I. Culture studies confirmed the ability of exogenous human and bovine beta 2-microglobulin to restore rapidly MHC class I antigen expression on transgenic cells. Because cell surface exchange of beta 2-microglobulin is less efficient between species with divergent beta 2-microglobulin sequences, the survival of transgenic 129 mouse liver cells in guinea pig (60% beta 2-microglobulin identity) and Xenopus (34% beta 2-microglobulin identity) hosts was investigated. Significant prolongation of MHC class I antigen-deficient liver cell xenografts was apparently only in Xenopus hosts. Furthermore, transplants of transgenic 129 mouse liver cells into isogeneic normal 129 mouse recipients showed evidence of rejection in seven of nine recipients, suggesting that transgenic donor cells also may be susceptible to lysis by host natural killer cells. PMID- 8475571 TI - Low-dose rapamycin potentiates the effects of subtherapeutic doses of cyclosporine to prolong renal allograft survival in the mongrel canine model. PMID- 8475572 TI - 31P magnetic resonance spectroscopy of the isolated human donor liver- feasibility in routine clinical practice and preliminary findings. PMID- 8475573 TI - Regeneration of the native liver after heterotopic liver transplantation for fulminant hepatic failure. PMID- 8475574 TI - Five-to-seven-day kidney preservation with aspirin and furegrelate. PMID- 8475575 TI - Evidence that thyroxine (T-4) is effective as a hemodynamic rescue agent in management of organ donors. PMID- 8475576 TI - Physiological models of orthotopic liver transplantation in the rat. PMID- 8475577 TI - [The independent variability of different karyotypic characteristics during the spontaneous neoplastic evolution of mouse embryo fibroblasts]. AB - The dynamics of some karyotype characteristics throughout the spontaneous neoplastic evolution of embryonal fibroblasts of different mouse strains was studied using a differential staining of chromosomes. The independent variability of chromosome modal numbers, the number of polyploid cells in the cell line, the number of chromosomal rearrangements within one cell, the activity of formation of different types of chromosomal rearrangements and the activity of interactions of the homologous chromosomes in 15 studied cell lines were revealed. Possible levels of variability regulations of different karyotype characteristics are discussed. PMID- 8475578 TI - [The cytodifferentiation of the rat spinal cord and neocortical neural elements when implanted into a peripheral nerve]. AB - Using electron microscopy, a study was made of the dynamics of development of the cerebral cortex and spinal cord in 14-day-old rat embryos implanted into the sciatic nerve of mature rats. It is shown that the implanted neural elements of the cortex and spinal cord survive for 8 months and differentiate from neuroepithelial cells and neuroblasts into young and mature neurons. In addition, the synaptogenesis and myelination were studied. Mature synapses in implants of the spinal cord were detected in 14 days, and in implants of the cortex in 21 days. The spinal cord and cortex implants displayed the first myelinated axons in 21 and 30 days, resp. Implants of the fetal spinal cord became mature earlier than the cortex implants. It has been stated that the processes of synaptogenesis and myelination in implants continue longer than in situ. PMID- 8475579 TI - [A possible pathway for mitogenic signal transmission during the contact stimulation of the multiplication of cultured cells]. AB - Cultured cells of the Japanese quail embryo were labeled with 3H-glucosamine, fixed, suspended and inoculated into built-up cultures of the homologous cells. The transfer of insoluble components of labeled cell surface into the cells of underlaying cell sheet was revealed. A decrease in the cell incubation temperature up to 4 degrees C blocks the process. The exchange of cell surface sites between contacting cells seems to be one of the possible ways of information transmission from one cell into another during contact regulation of cell proliferation. PMID- 8475580 TI - [The participation of endonuclease in the formation of extrachromosomal DNA and the possible mechanisms of the occurrence of gene amplification]. AB - We examined the extrachromosomal DNA (exDNA, Hirt fraction) in ethidium bromide sensitive and resistant cells of line L929. The exDNA amount is greater in the latter. The amount of exDNA in L929 cells makes 0.19% of the total cellular DNA; the exDNA amounts in cells, resistant to 5 and 50 micrograms/ml ethidium bromide are 0.22 and 0.33%, resp. Using labelling by BudR, it is shown that approximately 16% exDNA in L cells constituted amplified sequences to be excreting to the culture medium. The Zn-independent endogenous nuclease is activated in the resistant cells. The treatment with cycloheximide (50 micrograms/ml) resulted in the increase in the exDNA amount and in the activation of Zn-independent endonuclease. The data obtained suggested that the activation of Zn-independent endonuclease may lead to the increase in the exDNA amount and determine presumably a high rate of cell adaptability to environmental conditions. PMID- 8475581 TI - [The oxidative phosphorylation system of BHK-21 cells in suspension cultivation]. AB - The state of the oxidative phosphorylation system in intact and digitonin-treated BHK-21 cells in the lag-, logarithmic and stationary growth phases has been studied. It is shown that during the growth of cell culture the rates of oxygen uptake and the extent of coupling of oxidation and phosphorylation change significantly. PMID- 8475582 TI - [Extraordinary dangerous psychiatric patients]. PMID- 8475583 TI - [Decrees of dangerousness]. AB - According to the Danish Civil Commitment Law, very dangerous psychotic patients can be transferred from a general psychiatric department to the only psychiatric maximum security institution in Denmark. Denmark passed a new Mental Health Act in 1989, and according to this "decrees of dangerousness" are issued by the Ministry of Justice, followed by a court hearing. The Ministry of Justice asks the Danish Medico-Legal Council for a statement in all such cases. The number of patients who are transferred to the Maximum Security Institution according to these rules has increased greatly, the average number per year in the seventies being two to three patients, while in 1990, 11 patients were transferred. In the period 1985 to 1990, 39 cases concerning "decrees of dangerousness" were submitted to the Medico Legal Council. The Council did not find the conditions fulfilled in five cases, one case was invalidated by the court, and in two cases the requests were withdrawn. The increase in the number of "decrees of dangerousness" was equally divided between younger patients, i.e. up to 29 years old, the average duration of illness being about three years and elderly patients, i.e. 30 years or older the average duration of illness in this group being about 13 years. The majority of the patients suffered from schizophrenia. Among the younger patients, 11 of 18 had alcohol and/or drug abuse, which was only seen among three of the 21 elderly patients. Drug abuse increases the risk of dangerous behaviour among schizophrenics, and drug abuse among younger schizophrenics might be part of the explanation for the increasing number of "decrees of dangerousness".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475584 TI - [Syphilis meets AIDS. Syphilis seen in relation to the AIDS epidemic--a review]. AB - The incidence of syphilis in Denmark has changed within the last ten years. From being a relatively common disease at the end of the 1970's and beginning of the 1980's, the incidence has fallen considerably. It is assumed that the change is connected with the emergence of AIDS and the resulting increase in information and attention to sexually transmitted diseases. In the USA, after a fall in the beginning of the 1980's, the incidence of syphilis has risen markedly, particularly among heterosexual coloured people in large cities. Recently, there have been some reports claiming atypical syphilis in patients with HIV-infection. To date there are no controlled investigations to corroborate this notion. Seronegative syphilis or delayed seropositivity has been reported in certain immunosuppressed AIDS patients. Otherwise the syphilis serology of HIV-infected patients does not seem to differ essentially from HIV-negative patients. All patients with HIV infection should be counselled about syphilis and offered a test for syphilis, just as patients with syphilis should be encouraged to be tested for HIV antibody after informed consent. PMID- 8475585 TI - [Barrett esophagus]. AB - Barrett's oesophagus is a complication of chronic gastrooesophageal reflux disease and occurs in eight percent of patients with reflux symptoms. The diagnosis is made by endoscopy with biopsy. Dysplasia and early adenocarcinoma may involve only very small irregular areas of the oesophageal mucosal surface. Biopsies should therefore be taken from each quadrant at 1-2 cm intervals. The prevalence of dysplasia is about five to 16 percent, while the prevalence rate of oesophageal adenocarcinoma ranges from nought to ten percent and the incidence is one case per 87 patients years. No consensus concerning the treatment strategy for patients with metaplasia and low grade dysplasia has been achieved, because there is no conclusive proof as yet that screening programmes reduce the mortality from adenocarcinoma. Patients with high grade dysplasia should be controlled with endoscopy and biopsies every sixth month. Flow cytometry seems to be able to identify a subset of patients with an increased risk of oesophageal adenocarcinoma. PMID- 8475586 TI - [WR in patients with secondary syphilis and HIV infection]. AB - In recent years, there have been sporadic reports of aberrant manifestations of syphilis and a changed syphilis serology in AIDS patients, which might indicate difficulties in diagnosing the infection and monitoring the response to penicillin treatment. Six male patients aged 25 to 42 years with asymptomatic HIV infection and secondary syphilis were retrospectively compared with a control group of seven HIV-negative males aged 26 to 52 years with secondary syphilis. All patients presented with macular-papular exanthema of secondary syphilis; in all cases it was also their first episode of the disease. The median WR titre was 13 (range 11 to 20) in syphilis patients with HIV and nine (8 to 14) in the control group (p = 0.1). The median time until WR was found non-reactive after penicillin was four months (3 to 16) and five months (3 to 9), respectively (p = 0.8). Thus, in this small series there was no statistically significant difference in the WR-titres of asymptomatic HIV positive and HIV negative patients with secondary syphilis, although there was a tendency towards initially higher WR titre in the HIV group, as reported by others. PMID- 8475587 TI - [Complications of second-look surgery for ovarian cancer]. AB - All complications were registered in 139 consecutive second-look operations for ovarian cancer. Forty-one complications were registered in 33 patients, none lethal. The most frequent complications were anaemia requiring blood-transfusion (10.7%) and acute cystitis (4.3%). Other complications were seen with frequencies between 0.7 to 2.8 percent. No differences with respect to complications were found between patients with residual tumour versus those without, nor between patients where only biopsies were taken versus those who had organs removed. Although the patients were in clinical complete remission, 53% were found to have residual disease at second-look operation. PMID- 8475588 TI - [Duodenal cancer--illustrated by 5 cases, with special consideration to symptomatology, diagnosis and treatment]. AB - Over a period of 30 months we have seen five patients with duodenal cancer (four adenocarcinomas and one carcinoid-tumour). All patients are presented with a brief history of vague and non-specific symptoms. Diagnosis was established by endoscopy and biopsies. In one case, a Whipple's procedure was performed, and the patient is without evidence of tumour recurrence eight months later. Three patients could only be offered palliative surgery, of these, one is still alive two years after the operation, one (the patient with a carcinoid tumour) died three months postoperatively, and the third has only just recently been operated. The fifth patient died ten days after the diagnosis was confirmed, without any specific treatment. The different diagnostic methods available as well as the treatment and prognosis of duodenal cancer are discussed. We conclude that: 1) despite improved diagnostic procedures, the diagnosis of duodenal cancer is still difficult and delayed due to vague and non-specific symptoms, 2) the diagnostic procedure is endoscopy and biopsy. 3) the treatment is surgery and 4) the prognosis is poor in the majority of patients. PMID- 8475589 TI - [The MMR vaccination: no effect of feedback of vaccination scores in general practice]. AB - The purpose of this study was to assess the effect of graphic feed-back of vaccination scores (VS) for vaccination against measles, mumps and rubella (MMR) at the age of 15 months among practices in a Danish county. The study was designed as an intervention study, comparing VS for each practice with VS for the other practices in the county. The feed-back was evaluated qualitatively by use of a postal questionnaire. A majority of the 73 responding practices welcomed the graphic feed-back, regarded it as easily understood and requested similar information on an annual basis in the future. In 13 (18%) of the practices, the calculated VS was lower than the doctors had expected. The most frequent explanation for this discrepancy, given by 4 practices, was incorrect registration of the vaccination. Twenty-one percent of the practices had taken action to improve their performance after receiving the feed-back, but there was no significant improvement in VS in this group. In practices with low VS (< 70%) before intervention, there was no significant change in VS. The total VS for all practices in the county was 89% before and 88% after intervention. In conclusion, the feed-back had no observable effect on VS. Registration errors may explain why some practices had low VS. Feed-back with performance indicators may have better quantitative effect if accompanied by qualitative measures. PMID- 8475590 TI - [The role of hospital management in quality assurance activities at Danish hospitals]. AB - Quality assurance (QA) has been a main topic of debate within the Danish health care system over the last few years. In order to study the effects of this debate we conducted a survey of QA activities in all hospitals. This article is concerned with the role of the central hospital management in QA. Thirty-nine percent (forty-one) of hospital managements returned the questionnaire. Thirty two managements had initiated QA work in their hospitals, especially on topics concerning health care personnel, administration and organisation. Twenty-four managements had created goals for quality, only rarely were the goals followed up by quantitative methods. Seven managements had a special budget for QA activities. Those hospital managements who have initiated QA in their hospitals have selected key topics in order to facilitate the implementation of QA. PMID- 8475591 TI - [The role of hospital personnel in quality assurance activities at Danish hospitals]. AB - Over the last few years there has been considerable activity concerning quality assurance (QA) in health care. In order to investigate the actual consequences, we mailed a questionnaire to all Danish hospital managements, asking them to distribute it to leading doctors and nurses. 349 questionnaires from 51 hospitals were returned. The questionnaire was concerned with QA-activities, topics and methods, organisational aspects and attitudes amongst the professionals. Forty eight percent of all hospitals, evenly distributed over all hospital and department categories, were represented in the survey. Fifty percent of respondents were doctors, 40% nurses. Eighty-seven percent had started quality assurance activities, typically clinically oriented research where doctors were concerned, and typically projects concerning communication with patients when initiated by nurses. Both groups had many projects concerning personnel policy, especially educational aspects. 3% of the activities were concerned with patient satisfaction. Knowledge of quality assurance principles was not yet widespread among the professionals, but 87% expressed positive attitudes. There is a need to define the concept of QA and to spread knowledge of QA-methods, if a systematic approach to QA is to be implemented. PMID- 8475592 TI - [Lateral ligament ruptures of the ankle joint in young athletes]. AB - Treatment of lateral ligament rupture of the ankle has previously been primarily surgical. Immobilisation in a plaster cast has recently become more usual, and gradually this treatment is partially being replaced by immobilisation in adhesive elastic bandage. Operation of younger, athletic patients with large ruptures is, however, still recommended. It is inexpedient to operate these patients. They will be delayed for several weeks in their return to sport. PMID- 8475593 TI - [Low density lipoprotein (LDL) receptor-related protein internalizes and degrades uPA-PA1 complexes and is essential for embryo implantation]. PMID- 8475594 TI - [Local treatment of aphthae]. PMID- 8475595 TI - [Syphilis and contact tracing in the USA]. PMID- 8475596 TI - SPECTRA: a system for processing electron images of crystals. AB - SPECTRA is a program system that combines well tested and familiar algorithms and advanced graphics tools for (i) the display and indexing of the Fourier transform of images of crystalline specimens, (ii) refinement of the reciprocal lattice, (iii) output of amplitudes and phases of reflections and (iv) lattice distortion correction through cross-correlation map analysis. Because of the ease of identifying and indexing reflections, the user can include many reflections for reciprocal lattice refinement, leading to more accurate lattice determination. Automatic indexing is much faster than entering indices by hand, with less operator error. The user can run the procedure that corrects for lattice distortions with either standard parameters or storable parameters tailored to a particular specimen. SPECTRA's primary function is as a control program which acts as an interface between existing programs and the user. It was written in C with routines for the display, user interface and peak list search. Communication between the separate processes that make up SPECTRA is via the UNIX pipe mechanism and command files, the latter so that users may run, test or replace them or even run them as stand-alone programs outside this system. PMID- 8475597 TI - Cryo-crinkling: what happens to carbon films on copper grids at low temperature. AB - A study of the surface flatness of carbon films on copper grids used for cryo electron microscopy has been carried out using a Hitachi S-900 low-voltage SEM. Dramatic changes in flatness were observed after cooling from room temperature to -170 degrees C. The changes were similar both for carbon films that had been floated from a mica surface and for those initially deposited on the surface of plastic films. Results demonstrate that films prepared on copper grids that appear flat at room temperature become extensively, but reversibly, puckered at 170 degrees C. The linear thermal expansion coefficient (alpha) for copper is 16.2 x 10(-6)/degrees C and the puckering can be explained by assuming that the coefficient for amorphous carbon is substantially less. Measurements on grids made of titanium, molybdenum and tungsten (coefficients 8.5, 5 and 4.5 x 10( 6)/degrees C, respectively) showed significantly less puckering. PMID- 8475598 TI - Thickness determination of biological thin sections by multiple-least-squares fitting of the carbon K-edge in the electron energy-loss spectrum. AB - We show that the local thickness of biological thin sections can be measured by fitting the electron energy-loss spectrum of the plurally scattered carbon K edge, and that such measurements are consistent with the results obtained by a conventional method based on the relationship t/lambda alpha ln(It/I0). The new method allows the simultaneous measurement and/or mapping of both local thickness and core-level excitations (e.g. Ca L-edge) in this energy range (280-400 eV) without requiring the measurement of the zero-loss and the valence/plasmon excitations. PMID- 8475600 TI - Collection of papers dedicated to Professor Elmar Zeitler on the occasion of his 65th birthday. PMID- 8475601 TI - Measurement of low calcium concentrations in cryosectioned cells by parallel-EELS mapping. AB - Electron energy loss spectroscopy (EELS) in the scanning transmission electron microscope provides a high sensitivity for microanalysis of certain important biological elements such as calcium whose physiological concentrations in cells are rather low. Application of parallel-EELS mapping to the analysis of freeze dried cryosections of rapidly frozen tissue provides a means of detecting small amounts of calcium in structures with diameter approximately 50 nm. Detector pattern noise due to channel gain variations can be reduced by acquiring difference spectra at each pixel. By segmenting nitrogen maps that reflect the structure through the protein distribution it is possible to sum spectra from specific compartments. These are then processed by fitting reference spectra for the Ca L23-edge and the carbon background. It has been found that useful data can be collected at 100 keV beam energy from freeze-dried cryosections of cerebellar cortex cut to nominal thickness of 100 nm. The analysis results in a sensitivity of +/- 0.4 mmol Ca/kg dry weight with a total acquisition time of 400 s, a significant improvement over that achievable with energy-dispersive X-ray spectroscopy. PMID- 8475599 TI - Use of radial density plots to calibrate image magnification for frozen-hydrated specimens. AB - Accurate magnification calibration for transmission electron microscopy is best achieved with the use of appropriate standards and an objective calibration technique. We have developed a reliable method for calibrating the magnification of images from frozen-hydrated specimens. Invariant features in radial density plots of a standard are compared with the corresponding features in a "defocused" X-ray model of the same standard. Defocused X-ray models were generated to mimic the conditions of cryo-electron microscopy. The technique is demonstrated with polyoma virus, which was used as an internal standard to calibrate micrographs of bovine papilloma virus type 1 and bacteriophage phi X174. Calibrations of the micrographs were estimated to be accurate to 0.35%-0.5%. Accurate scaling of a three-dimensional structure allows additional calibrations to be made with radial density plots computed from two- or three-dimensional data. PMID- 8475602 TI - Concentration evaluation of chromatin in unstained resin-embedded sections by means of low-dose ratio-contrast imaging in STEM. AB - Quantitative STEM with the imaging mode of ratio-contrast was investigated in order to evaluate the local concentration of DNA in situ for different kinds of DNA plasms in terms of intracellular packing densities (p.d.). The ability of ratio imaging to suppress thickness variations provided the basis to use unstained sections from cryofixed and freeze-substituted material. The DNA p.d. within the nucleoid of E. coli was determined to be about 100 mg ml-1. Quantitative data concerning the p.d. of DNA in condensed eukaryotic chromatin assuming equal amounts of DNA and protein were evaluated for the first time: approximately 400 mg ml-1 chromatin which corresponds to 200 mg ml-1 DNA. The p.d. of DNA in chromosomes from the dinoflagellate Amphidinium carterae, a eukaryote devoid of histones and with only small relative amounts of histone-like protein, was also found to be of the order of 200 mg ml-1. The highest p.d. of DNA was measured for the head of the bacteriophage T4 with more than 800 mg ml-1, in fair agreement with previous calculations. The results provide further support for a condensation mode of low protein chromatins that involves a liquid crystalline organization of the DNA filaments. PMID- 8475603 TI - Flopping polypeptide chains and Suleika's subtle imperfections: analysis of variations in the electron micrograph of a purple membrane crystal. AB - Patch averaging, a method of data analysis combining correlation averaging with multivariate statistical analysis, was applied to a high-resolution image of a purple membrane thin crystal. The observed variational patterns fall in two categories: non-crystallographic, related to small electron-optical distortions of the microscope, and crystallographic, conceivably related to variations in the locations of flexible segments of the polypeptide chain on the surface of the membrane. PMID- 8475604 TI - Prospects for using an IVEM with a FEG for imaging macromolecules towards atomic resolution. AB - Specimen preparation and imaging techniques for biological macromolecules have been improved to the point where attention to the electron-optical imaging conditions becomes a significant factor for achieving high resolution. A field emission gun (FEG) can provide an illumination source with a better spatial and temporal coherence suitable for imaging near atomic resolution. Our computational analysis of carbon film images taken between Scherzer focus and 1.1 microns underfocus (20x Scherzer focus) with the Hitachi 200 kV microscope with a cold field emission gun shows detectable contrast beyond 3.5 A resolution. In biological imaging, a large defocus is often used to optimize the low-resolution contrast in order to facilitate the subsequent steps in computer reconstruction. An intermediate-voltage electron microscope (IVEM) would optimize the contrast at high resolution by reducing the temporal coherent effects. In theory, the IVEM would give a greater depth of field so that large macromolecular assemblies such as viruses and cellular structures can be interpreted and reconstructed reliably using the projection approximation. These experimental and theoretical considerations provide a rationale for designing a future IVEM with a FEG suitable for biological macromolecule imaging close to atomic resolution. PMID- 8475605 TI - Size of the export channel in the flagellar filament of Salmonella typhimurium. AB - The size of the putative export channel in the bacterial flagellar filament appears small (25 A) in studies done by electron microscopy but large (60 A) in studies done by X-ray diffraction. We have undertaken additional studies by electron microscopy to examine some of the possible causes of the difference. A comparison of three-dimensional image reconstructions of native and reconstituted filaments rules out the presence or absence of flagellin monomers in the export channel as the source of the variation in apparent channel size. The channel seen in reconstructions from both kinds of filaments is 25 A in diameter. The difference in the previous studies is more probably a result of artifacts introduced in either the X-ray or the electron microscopical methodology. Comparisons of three-dimensional reconstructions from images of filaments embedded in various stains (anionic, cationic and neutral) and in ice, taken at a range of defocuses, rule out the two most likely sources of artifact in electron microscopy (i.e., staining artifacts and defocus phase contrast). Based on these studies we suggest that the channel seen in the image reconstructions is free of exported flagellin monomers, that its true diameter is about 25 A, and, therefore, that the flagellin monomer must be unfolded to pass along it. PMID- 8475606 TI - [Urinary diversion: pathophysiological principles]. PMID- 8475607 TI - [Diagnostic evaluation of acute scrotum--testicular perfusion scintigraphy]. AB - The method of and the results obtained with testicular scintigraphy in the differential diagnosis of acute scrotal pain are described. Both sensitivity and specificity were found to be high and in excess of 90%. Misinterpretation of findings is rare and is seldom reported except in case reports. Normal findings usually genuinely reflect absence of disease, and only in the case of suboptimal imaging conditions they might correspond to a false-negative finding in the presence of acute torsion. Chronic torsion may be missed on scintigraphy because of intermediate normalization of arterial perfusion at the time of the investigation. Missed torsion presents a characteristic activity pattern. The halo sign is a proven sign of avitality of the testicle. Orchitis and epididymitis are correlated with hyperperfusion and hyperaemia and are reliably diagnosed by scanning. When testicular scintigraphy is needed immediate availability is essential. In a nuclear medicine department with standard equipment, the investigation can be started within 5 min; it takes about 15 min to perform and the findings can be evaluated within another 5 min. Acute testicular torsion that has already been reliably diagnosed by clinical examination is not an indication for testicular perfusion scintigraphy. This diagnostic procedure is, however, valuable if the clinical findings are equivocal and, especially, if a conservative treatment is planned. PMID- 8475608 TI - [Immunoscintigraphy in inflammatory and malignant diseases. anti-leukocyte and anti-tumor antibodies]. AB - Antibody-labelled granulocytes, antigranulocyte antibodies and radiolabelled immunoglobulin can reliably visualize foci of infection; their use in urologic inflammatory disorders is rare. In the diagnosis of urologic tumours anti-CEA immunoscintigraphy of urinary bladder cancer seems to be superior to conventional imaging techniques in sensitivity and specificity. Experience with immunoscintigraphy in non-seminomatous germ cell tumours and prostate cancer are limited; immunoscintigraphy of renal cell cancer is still in the experimental stage in clinical medicine. PMID- 8475609 TI - [Follow-up after kidney transplantation. Sequential functional scintigraphy with technetium-99m-DTPA or technetium-99m-MAG3]. AB - Complications following renal transplantation are associated with transplant dysfunction; their frequency and the nonspecificity of clinical symptoms underscore the importance of choosing the correct diagnostic procedure. Sequential function scintigraphy with technetium-99m-MAG3 is noninvasive and facilitates the diagnosis of different types of organ rejection, of drug-induced malfunction and of surgical complications. PMID- 8475610 TI - [Nuclear medicine diagnosis of adrenal gland diseases]. AB - Localization procedures are required in adrenal diseases after biochemical confirmation of hormonal excess. Whereas computed tomography, ultrasound and--in rare cases--also magnetic resonance are needed to image the morphological abnormalities and the anatomy of neighbouring structures, adrenocortical and adrenomedullary scintigraphy is dependent on a functioning adrenal gland. Adrenocortical scintigraphy has the advantage of being able to differentiate between unilateral adenoma and bilateral hyperplasia in patients with primary hyperaldosteronism. It is of minor significance in patients with Cushing's syndrome or hyperandrogenism. In patients with catecholamine-producing tumours scintigraphy with radioiodine-labelled meta-iodobenzylguanidine (MIBG) may detect intra- and extra-adrenal, uni- and bilateral or multilocular, benign and malignant lesions. In patients with malignant but inoperable phaeochromocytoma, therapy with high doses of MIBG may improve clinical symptoms and reduce tumour volume. PMID- 8475611 TI - [Diagnosis of urine transport disorders. Diuresis renography]. AB - Congenital urinary tract malformations are frequently the cause of urinary transport disturbances. However, not all the malformations or obstructions presenting sonographically as hydronephrosis have to be treated surgically. The Whitaker test, an invasive diagnostic procedure to establish the urodynamic relevance of an obstruction, does not provide a reliable estimate of prognosis; spontaneous cures in cases of obstruction have been reported. Diuresis renography offers several advantages as compared with the Whitaker test, for example a more physiological basis, less observer dependency, better reproducibility and--last but not least--non-invasiveness. However, diuresis renography has to be carried out according to a strictly standardized protocol. Sufficient hydration (20 mg/kg body weight) and bladder catheterization (to rule our reflectory transport disturbances) are mandatory. Today, 123I-OIH or 99mTc-MAG3 are the radiopharmaceuticals of choice; the activity for children has to be reduced in relation to body surface. To stimulate diuresis, furosemide (0.5-1 mg/kg of body weight) has to be given. For the evaluation of diuresis renography, sequential scintigrams as well as functional curves have to be used. It is strongly recommended that diuresis renography be combined with clearance determinations separately for the two kidneys. The interpretation of diuresis renography should not rely only on quantitative curve parameters but--above all--on visual analysis of the functional curves. However, in cases of proven obstruction, diuresis renography--like the Whitaker test--cannot accurately predict the prognosis in any individual case. If renal function is normal and there is no difference between the left and the right kidney, a wait-and-see attitude seems to be justified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475612 TI - [Combined ultrasound and roentgen localization in ESWL. Initial clinical experiences]. AB - Interdisciplinary use of extracorporeal shock-wave lithotripsy with sonographic or fluoroscopic guidance has become a routine procedure in clinical practice, for both urolithiasis and cholecystolithiasis. Therefore, newly developed systems with combined locating devices are gaining in importance. A primary sonographically guided lithotripter was extended by a mobile X-ray system. The results were compared with those obtained with a first-generation lithotripter. The results show that sufficient disintegration of stones throughout the urinary tract is possible with both systems. The retreatment rate with both lithotripters was 30% when stone size was comparable. No essential differences in treatment time, shockwave energy and pain were found. The easy localisation of radiolucent stones, convenient positioning of the patient and successful localisation of ureteral stones near to the spine are advantages of the MPL 9000 X. On the other hand, the technically simpler fluoroscopy system and greater ease of electrode changing are advantages of the HM3 Lithotripter. Altogether, differences in the application of the two systems are slight and insignificant except in special cases. PMID- 8475613 TI - ["Single potential analysis of cavernous electric activity" (SPACE). Findings before and after surgical dissection of the cavernous nerves within the scope of radical prostatectomy]. AB - Single potential analysis of cavernous electric activity (SPACE) is said to give information on the integrity of the central and peripheral parts of the autonomic nervous system insofar as it is involved in erectile function. A total of 30 patients who underwent radical prostatectomy with simultaneous severance of the cavernous nerves as treatment for locally advanced cancer were investigated by SPACE before and after the operation. The findings were compared to the those recorded on two different dates in 20 age-matched men who had not undergone surgery and in whom there was no evidence of any lesion of the autonomic nervous system. Even in this control group, few reproducible results were found. Nevertheless, with reference to the items "number of wedges" (i.e. monophasic elements with amplitudes of 25-100 microV) and "maximum amplitudes" of SPACE potentials there was a more than change correlation of the values on the two test dates, which was not found in the prostatectomy group. Although this difference between the two groups investigated was statistically significant, these findings cannot be interpreted as an effect of autonomic denervation of the cavernous bodies. This is attributed to the fact that the postoperative results in the prostatectomy group were more similar to the findings in the control group than to the preoperative measurements taken while the autonomic innervation was still intact. Therefore, our investigations lead us to conclude that routine application of SPACE as a direct check on the integrity of the autonomic nerve fibres involved in erectile dysfunction is not justified at present. PMID- 8475614 TI - [Autotransplantation of the kidney. Indications and results]. AB - Renal autotransplantation is an established but rarely used therapy in cases of renal vessel lesions, tumours of the kidney and ureter, long-distance ureter lesions, complex nephrolithiasis and retroperitoneal fibrosis. The indications and results of renal autotransplantation are discussed using three case reports and compared to the literature. In cases of central intrarenal tumours and aneurysms of the kidney, autotransplantation is indispensible in order to save the organ. For long-distance ureter lesions as well as for retroperitoneal fibrosis, autotransplantation of the kidney gives excellent results. In difficult clinical situations ileum segment interposition is an alternative treatment. PMID- 8475615 TI - [Quantitative nuclear medicine kidney diagnosis with kidney tubule traversing radioisotopes]. AB - In modern nuclear medicine, renal function scintigraphy has been improved and its range of applications extended by the development of new radiopharmaceuticals (iodine-123-hippuran, technetium-99m-MAG3) combining the properties of short half life, favourable radiation energy and high renal clearance. Three significant advantages recommend the use of scintigraphic methods: 1. Being non-invasive and non-nephrotoxic, the examinations do not affect the patient. The radiation exposure the patient is subjected to is about the same as with a comparable X-ray investigation or, with respect to the reproductive glands, even lower. Allergic reactions do not occur. 2. In contrast to the situation with other imaging methods, the functional defect itself (and not only secondary changes in the morphology) can mostly be detected. Not only diffuse alterations, but also defined functional lesions of a small part of a kidney, can be diagnosed. 3. Various renal parameters can be calculated more accurately than with any other routine clinical method. The radioisotopic methods discussed yield reliable results with excellent reproducibility concerning glomerular filtration rate, effective renal plasma flow, side-to-side functional ratio, renal perfusion, and urine drainage. Most of these parameters can be obtained by means of a single investigation. These radioisotopic methods make it possible to detect or exclude a wide range of functional lesions of the kidneys and the urinary tract, which are often due to non-specific symptoms. In addition, they allow answers to highly specific clinical and scientific questions in nephrology and urology. PMID- 8475616 TI - [Nuclear medicine diagnosis and therapy in urology. Diagnosis of bone metastases]. AB - Bone scintigraphy with 99mtechnetium-labelled polyphosphonates is the most sensitive test for early detection of skeletal metastases. Bone metastases are a major factor in prognosis and have a considerable influence on the therapy selected. In patients with prostate cancer, we recommend routine bone scintigraphy in the initial staging. Follow-up bone scans are indicated whenever a patient develops pain, an elevated level of acid phosphatase, or a rise in prostate specific antigen (PSA). Routine bone scans are not necessary for the initial staging of patients with renal cell carcinomas, bladder carcinomas and testicular tumours. Scans should be routinely performed, however, in patients with bone pain or elevated alkaline phosphatase or when radiological findings are inconclusive. Bone scanning is necessary in patients with neuroblastoma, both for the initial diagnosis and during follow-up in all cases with known skeletal involvement. In addition, bone scintigraphy should be performed in cases of recurrent or suspected malignant phaeochromocytoma as a complement to scintigraphy with iodine-123- or iodine-131-MIBG, respectively. Even though skeletal scintigraphy is a very sensitive test, it lacks specificity. This can be compensated, however, by careful interpretation of the scan in the light of the patient's history and the clinical findings. As a positive side-effect, bone scanning--especially in the form of multiphase scintigraphy--may detect renal abnormalities, concurrent diseases or complications in the upper or lower urinary tract. If scintigraphic findings are doubtful, plain film radiographs are required or, in selected cases, bone biopsy must be performed. PMID- 8475617 TI - [Biochemical and physiologic properties of strains of Propionibacterium acnes isolated from the rumen of calves and lambs]. AB - Nineteen strains of Propionibacterium acnes isolated from the rumen wall of calves and lambs were subjected to examinations. Their biochemical characteristics and antibiotic resistance were evaluated while 10 strains were sensitive to all tested antibiotics. Urease activity was recorded in 20% of the examined strains with the mean value 3.42 +/- 0.97 nkat/ml/h. Proteolytic activity was observed in all the examined strains. The mean value of lactate dehydrogenase activity was 4.96 +/- 1.01 nkat/ml. The production of volatile fatty acids in the course of glucose fermentation was also tested. On the basis of the values of adherence index the strains were evaluated as medium adherent with affinity to rumen epithelial cells. PMID- 8475618 TI - Isolation and functional studies on feline bone marrow derived macrophages. AB - In this report, we describe an in vitro culture method for feline bone marrow cells, which yields large numbers of quiescent macrophages after 14 days of culture. The bulk of the cultured cell population consists of macrophages as assessed by morphology, macrophage specific cytochemistry, and phagocytosis. The remaining cells were lymphocytes, bone marrow stromal cells, fibroblasts and occasional polymorphonuclear leukocytes. While resting cells produced no detectable interleukin 1, stimulation with lipopolysaccharide (LPS) induced the production of biologically active interleukin 1. After 6 h LPS stimulation, mRNA for tumor necrosis factor alpha and interleukin 1 beta was detectable. The absence of mRNA in unstimulated cells indicates cultured macrophages were not activated until stimulated by LPS or plastic adherence. This approach provides a useful means to measure potential modulatory effects by virus infections or other agents upon feline macrophage gene expression. PMID- 8475619 TI - Effects of hypothyroidism with treatment of an anti-thyroid drug, propylthiouracil on immune responses in chickens. AB - The effect of a wide range of doses of propylthiouracil (PTU, 0.01-5%) on the immune responses of young male chickens was examined. One-day-old chickens were rendered hypothyroid by PTU supplemented in the feed for 4 weeks. At all doses PTU treatment caused a significant dose-related reduction in body weight (except at 0.01%) and in relative lymphoid organ weights. Skin response to phytohemagglutinin (PHA) was significantly greater in the chickens treated with low doses of PTU (0.01-0.1%) and significantly less in the chickens treated with high doses of PTU (1.5-5%) than that in control chickens. Number of splenic plaque forming cells (PFC) to sheep red blood cells (SRBC) was significantly increased in the chickens treated with low doses of PTU. Concentrations of serum 3,3',5-triiodothyronine (T3) and thyroxin (T4) were significantly lower in the chickens treated with all doses of PTU. Addition of T3 to the feed supplemented with 0.01% PTU replaced the serum T3 concentration and reduced the skin response to PHA and the number of the splenic PFC. These data confirm our previous observations that a low dose of PTU enhances and a high dose suppresses the immune responses of young male chickens. PMID- 8475620 TI - In vitro and ex vivo responses of bovine lymphocytes to hypodermin C, an enzyme secreted by Hypoderma lineatum (insect oestridae). AB - The aim of this work was to determine if Hypodermin C (HC), an enzyme secreted by Hypoderma spp. larvae during their migration, is able to depress the lymphocyte response to mitogens and antigens. HC, when added to the lymphocyte culture, was able to influence the response of naive-calf lymphocytes to phytohemagglutinin. Secondly, injections of HC to uninfested and previously-infested cattle did not modify the proliferative response of the lymphocytes of these animals to mitogens. Thirdly, injections of HC to infested cattle did not negatively influence the specific humoral and cellular responses. PMID- 8475621 TI - An analysis of 38 cases of low-grade cerebral astrocytoma in adults. AB - We retrospectively reviewed 38 cases of low-grade non-pilocytic astrocytoma diagnosed at the Charleston Area Medical Center between 1957 and 1987. All patients underwent craniotomy (total resection in 8 and subtotal in 24) or stereotactic needle biopsy (6 patients). Twenty-eight patients (74%) received radiotherapy, 25 of whom received > or = 5,000 cGy. The median survival of all patients was 46 months and nine patients (24%) survived > or = 5 years. Patients under age 40 had a longer survival than those age 40 or older (59 months vs. 30.5 months, p < .05). There was no significant difference in mean survival between those who received and those who did not receive radiotherapy after incomplete surgical resection (49 months vs. 53 months, p = 1.00). Of the 29 deaths, 15 were due to malignant transformation to a high-grade glioma and 12 to recurrent low grade glioma. Since the role of radiotherapy is unclear, it is important that patients with low-grade glioma participate in clinical trials. PMID- 8475622 TI - Indications for carotid endarterectomy. AB - Stroke is a major health problem in the United States. Carotid endarterectomy has been performed to prevent stroke in symptomatic and asymptomatic patients with carotid atherosclerosis. The rationale for this approach has been questioned recently and several studies were begun to determine the proper role of surgery. The initial results from studies of symptomatic patients demonstrate that surgery is urgently indicated if stenosis is at least 70%, but not if it is less than 30%. Patients with intermediate amounts of stenosis are still being evaluated. Early evidence suggests that surgery is not indicated for asymptomatic patients, but two major trials are still in progress. Surgeons performing this procedure must demonstrate low perioperative morbidity and mortality. In addition, the use of ultrasound as a screening procedure is being re-evaluated. We suggest rapid referral and evaluation of symptomatic patients with angiography, and treatment of asymptomatic patients with aspirin. PMID- 8475623 TI - Nd:YAG laser surgery of venous malformations. AB - Venous malformations are prevalent in the head and neck. These anomalies are difficult to eradicate by conventional methods due to excessive bleeding and imprecise excision. This article details how the success rate for treating low flow venous malformations was 100% in 24 patients who underwent Nd:YAG surgery. PMID- 8475624 TI - Making sense. PMID- 8475625 TI - If elective abortion is not wrong, nothing is wrong. PMID- 8475626 TI - [Diabetes mellitus and carbohydrate metabolism in primary hyperparathyroidism]. AB - It is generally known that patients with primary hyperparathyroidism (pHPT) feature disturbances in carbohydrate metabolism and hypertension. The incidence and prevalence of frank diabetes mellitus is significantly increased in these patients. The etiology and pathogenesis of the vascular and metabolic aberrations in this condition are still unclear. Glucose intolerance in pHPT is characterized by severe insulin resistance associated with pancreatic beta cell hypersecretion of insulin. Hypercalcemia is thought to be mainly responsible for the impaired glucose metabolism. However, several studies demonstrated that hypophosphatemia can also induce insulin hypersecretion and impair peripheral glucose uptake. Hypertension in primary hyperparathyroidism is mainly attributed to hypercalcemia. However, high peripheral insulin levels are also proposed to contribute to the development of essential hypertension and hyperinsulinemia per se is regarded as an important independent cardiovascular risk factor. After parathyroidectomy and decrease of the calcium levels to within the normal range, the blood pressure levels of the patients with pHPT normalised very quickly, whereas normalization of the high peripheral insulin levels was only found in a subgroup of patients. Thus, hypercalcemia seems to be mainly responsible for hypertension in primary hyperparathyroidism. Another important, yet unresolved issue is the question as to whether or to which extent the disturbances in glucose homeostasis are reversible after surgical correction of pHPT. At an early stage of the disease, insulin resistance and insulin hypersecretion are fully reversible after parathyroidectomy, whereas in patients with long-standing primary hyperparathyroidism and severely impaired glucose tolerance the metabolic disturbances will only partially improve. These results argue for improved screening to identify asymptomatic patients with primary hyperparathyroidism and for early surgical intervention in this disease. PMID- 8475627 TI - [Serum magnesium, serum potassium and arrhythmia profile in patients with acute myocardial infarct]. AB - In 176 patients with acute myocardial infarction (AMI) serum magnesium concentration (MGK) and serum potassium concentration (KK) were analysed during the first 48 hours after AMI. The patients rhythm was continuously recorded. In a subgroup of 70 patients a signal averaging-ECG was performed. 4.5% of the patients had a low, 55.7% a normal and 39.8% a high MGK. 14.8% of the patients had a low, 80.1% a normal and 5.1% a high KK. Ventricular arrhythmias > or = Lown IV b were found in 25% of the patients with low MGK, in 38.8% with normal and in 52.9% with high MGK. 50% of the patients with low, 62.2% with normal and 61.3% with high MGK had late potentials. There was no relation between hypomagnesemia and ventricular arrhythmias as between hypomagnesemia and late potentials. Thus, hypomagnesemia in AMI patients is rare and does not correlate with ventricular arrhythmia or delayed ventricular potentials. PMID- 8475628 TI - Bone mineralization and plasma concentrations of electrolytes in healthy subjects after exposure to hypokinesia and hyperhydration. AB - The objective of this investigation was to determine bone mineralization and concentrations of electrolytes in blood plasma of physically conditioned volunteers after exposure to hypokinesia (decreased number of steps/day) and daily hyperhydration. The studies were performed on 30 physically conditioned volunteers (mean VO2 max 67 ml/kg-1 x min-1 age range 19-24 years) after exposure to 364 days of hypokinesia (HK). Prior to their exposure to HK all volunteers were long-distance runners who covered on average 10,000 steps per day. All subjects were divided into three equal groups: the 1st group was subjected to HK and consumed daily fluid and salt supplements (water 26 ml/kg body weight and sodium chloride 0.16 g/kg body weight), the 2nd group submitted to pure HK, and the 3rd group continued to engage in long-distance running and served as control. For the hypokinetic effect the 1st and 2nd group of volunteers were restricted to an average of 1000 steps/day. After exposure to HK the changes in bone mineralization and blood plasma concentrations of magnesium and calcium were determined. In hyperhydrated volunteers bone mineralization increased and content of electrolytes in blood plasma decreased, while in hypokinetic volunteers the electrolyte levels increased significantly and bone mineralization decreased significantly. It was concluded that daily fluid an salt supplementation may be used to attenuate changes in bone mineralization and blood plasma concentrations of electrolytes induced by prolonged restriction of motor activity of highly trained athletes. PMID- 8475629 TI - [Measuring drinking water fluoridation in Vorarlberg]. AB - A pilot study was undertaken in Vorarlberg to determine the concentration of fluoride ions in drinking water. The results showed that 91.3% of the population was supplied by drinking water containing under 0.3 ppm fluoride and the remaining 8.7% by drinking water containing 0.3-0.6 ppm fluoride. Hence, the fluoride concentration was too low to prevent caries in all areas of Vorarlberg. Exogenous fluoridation of the drinking water or table salt in all districts of Vorarlberg is discussed. Measurements are planned for the whole of Austria, which may lead to a general recommendation for fluoridation of the water or salt nationwide. PMID- 8475630 TI - [Anaphylactic reaction in streptokinase therapy]. AB - Streptokinase is used worldwide as thrombolytic agent. Indications are deep vein thrombosis, arterial thrombosis and embolism, arteriovenous cannula occlusions, acute coronary artery thrombosis, and acute renal vein thrombosis. The major drawback in comparison with other thrombolytic drugs is its antigenicity. Allergic reactions have been reported but the underlying mechanisms have not yet been fully elucidated. A 58 year-old man with acute myocardial infarction developed an anaphylactic reaction immediately after commencement of streptokinase infusion, although immunological laboratory findings were not affected. The patient had no history of prior exposure to streptokinase, infections with streptococci, or chronic allergic reactions. 2 months after streptokinase therapy increased plasma levels were detected of specific IgG antibodies to streptokinase. The levels of specific IgE antibodies to streptokinase and other anti-streptococcal antibodies were within the normal range. A prick test performed 4 months later with 100 I.U. streptokinase was unremarkable. The problems of such allergic reactions are discussed on the basis of this case report and a review of the literature. PMID- 8475631 TI - [Etiology and pathogenesis of type I diabetes]. AB - A large body of evidence supports the hypothesis that type I diabetes is an autoimmune disease. The development of type I diabetes can conceptually be divided in three stages: 1. genetic susceptibility, 2. pretype I diabetes with beginning beta-cell destruction and insulitis, and 3. clinical overt type I diabetes. During stage 2, an unknown "triggering event" leads to inflammation and active autoimmunity towards beta cells. In this chapter, recent developments concerning genetics and environmental factors, pathogenic mechanisms, prediction, and immunotherapy of type I diabetes will be reviewed. PMID- 8475632 TI - [Metabolic syndrome--bridge to type II diabetes]. AB - The metabolic syndrome (syndrome X) is characterized by elevated insulin levels, obesity of the android type, disturbed lipid metabolism with increased triglycerides (VLDL elevated, HDL decreased) and an association with hypertension. The cause of this syndrome appears to be an insulin resistance of the skeletal muscle. The molecular mechanism leading to skeletal muscle insulin resistance is not understood, however an abnormality of signal transduction from the insulin receptor to glycogen synthase is suggested. It is believed that this syndrome represents a potentially prediabetic situation. Furthermore it is believed that this syndrome gives rise to cardiovascular complications in certain predisposed populations. PMID- 8475633 TI - [Educating the diabetic patient as a basis for therapy]. AB - Since the late 1970's, diabetes therapy has been revolutionized and, in fact, new treatment strategies have been initiated by patient education and the resulting self-monitoring of the patient. The modern management of the chronic lifelong disease diabetes mellitus not only requires the prescription of the appropriate nutritional and pharmacologic regimen by the physician, but also intensive education and counselling of the patient. It is the diabetic himself who ultimately has to secure the treatment as given by the physician in daily life and--in so doing--has to provide a great deal of self-care and self-control. Meeting the individual treatment goal is largely dependent upon the cooperation and motivation of the patient, with the physician as both the sympathetic and critical counterpart. Today, education is the indispensible prerequisite for the limited well-being and health of diabetics and, at this end, education is equal to therapy. PMID- 8475634 TI - [Nutritional therapy in diabetes mellitus]. AB - Most aspects of the nutritional therapy of diabetes mellitus apply equally to IDDM and NIDDM patients and are also appropriate for people with high risk of cardiovascular diseases. A restriction of energy, a reduction of saturated fatty acids as well as of alcoholic drinks and simple sugars are the most important measures. This modification of nutritional intake together with increased fibre consumption is not only appropriate to avoid hyperglycaemia in diabetic patients but has also its benefits in patients presenting with the metabolic syndrome (possible reduction of hyperinsulinaemia, hypertension and hyperlipoproteinaemia). Diabetic patients should have regular screening for microalbuminuria. At first signs of an early stage of nephropathy patients should be advised to restrict their protein intake. About 50% of daily energy intake should be derived from carbohydrates and fat intake should be no more than 35% of total energy (saturated fatty acids less than 10% of energy). Carbohydrate exchange units are usually not necessary in NIDDM patients. In addition diabetes specialty foods are not an essential part of the nutritional therapy. The success of the nutritional therapy in diabetic patients is substantially dependent upon qualified counselling and education of the patients by the physician (as far as possible with the assistance of a dietitian). PMID- 8475635 TI - [Differential therapy with oral antidiabetic drugs]. AB - The more than 3 million type II diabetics in Germany constitute a true therapeutic challenge. Type II diabetes mellitus is part of the so-called metabolic syndrome characterized by the problem of insulin resistance/hyperinsulinemia. Treatment of type II diabetes aims at reducing insulin resistance. Oral antidiabetic management must be based on diabetic diet, in conjunction--if needed--with monotherapy with acarbose or metformin. Only after exhausting these principles of management, acarbose or metformin may be combined with sulfonylurea. Primary monotherapy with insulinotropically acting sulfonylureas is, in most cases, no longer appropriate as we are learning more about the pathophysiology of metabolic syndrome. PMID- 8475636 TI - [Combination therapy of oral antidiabetic drugs with insulin]. AB - The treatment of type II diabetes should not only concentrate on blood glucose levels but also should take symptoms like insulin resistance, hyperinsulinemia, low HDL-cholesterol, high VLDL, and systemic hypertension into consideration. These symptoms are well described by the metabolic syndrome and are known to be risk factors of macroangiopathy. In obese type II diabetic patients weight loss by caloric restriction is the most essential therapeutic step. Retarding intestinal carbohydrate uptake glucosidase-inhibitors are able to lower postprandial blood glucose levels without stimulating insulin secretion. The biguanide metformin is suitable to diminish peripheral insulin resistance, gluconeogenesis, and intestinal glucose absorption on cellular mechanisms others than betacytotropic effects. In non obese type II diabetic patients sulfonylureas are advantageous because of meal related stimulation of endogenous insulin which runs the physiological way with first pass through the liver. Therefore, sulfonylurea treatment should be continued when secondary failure indicates the need for exogenous insulin. In accordance with the course of type II diabetes in secondary failure insulin should be added to sulfonylureas in as small amounts as possible to ameliorate poor metabolic control. Thus iatrogenic hyperinsulinemia and resulting insulin resistance can be largely avoided. If there is any long term benefit when different oral antidiabetic agents are administered together with insulin has to be evaluated in further clinical studies. PMID- 8475637 TI - [Reliable and new aspects of insulin therapy]. AB - New findings concerning the dynamic of insulin secretion, insulin action and pharmacokinetics of insulin preparations have caused a complete change of insulin therapy in diabetes mellitus (basis-bolus-concept). At the same time, the discrepancy between insulin substitution and physiologic conditions becomes evident. Even the use of human insulin or the development of insulin-pens and pumps does not influence that fact. From the beginning of insulin therapy till now the subcutaneous injection of insulin is the safest and easiest way of application. By means of modified insulins (bioengineering) the physico-chemical process of insulin resorption could be elucidated in the last 4 years. In clinical experiments the intraperitoneal and nasal insulin administration is tested extensively. In the field of the intensified insulin therapy including near normoglycemic therapeutic goals the awareness of hypoglycemia is of particular importance. PMID- 8475638 TI - [Diabetic microangiopathy]. AB - On the whole, diabetic microangiopathy can be understood as the clinical renal retinal syndrome. About 10% of all diabetics die of end-stage renal failure, more frequent in IDDM. With an incidence of 14% diabetic retinopathy is one of the major causes of blindness in adulthood. In the non-proliferative state, the pathological changes are limited to the retina, whereas the alterations affect both retina and vitreous in the proliferative state. Photocoagulation is the treatment of choice. If photocoagulatory treatment is not possible because of cataract, vitreous surgery (pars-plana vitrectomy) could improve visual prognosis. The clinical features hypertension, proteinuria and finally renal failure define the term "diabetic nephropathy". The increased intraglomerular pressure is the main pathological alteration of incipient nephropathy. Microalbuminuria essentially determines the prognosis: in IDDM it concerns the incidence of a manifest nephropathy, in NIDDM the excessively increased incidence of cardiovascular mortality. Sonographically, the kidneys are large with bright and wide parenchyma. Along with the development of end-stage renal disease the kidney size diminishes. According to Mogensen, nephropathy is divided into five stages: Stage 1, the early stage, is defined by hypertrophy and hyperfiltration. Stage 2 shows incipient structural changes without any clinical findings. Stage 3 is characterised by persistent microalbuminuria. Stage 4 leads to increasing renal failure and stage 5 to end-stage renal disease and the necessity of dialysis treatment. Incipient nephropathy demands a strict treatment of both hypertension and diabetes. In the meantime, ACE inhibitors are the treatment of choice. In case of dialysis treatment continuous ambulant peritoneal dialysis (CAPD) is usually preferred. PMID- 8475639 TI - [Macroangiopathy in diabetes mellitus]. AB - Although there is no evidence of effectiveness of interventional trials concerning macroangiopathy in diabetes mellitus, the focus of primary prophylaxis is based on the treatment of risk factors and optimal adjustment of metabolic parameters. This should contain the prophylaxis of the diabetic foot (foot care, teaching, pressure bearing) in the neuro-ischaemic risk patient. In the secondary prophylaxis acetylsalicylic acid has been proven as effective in the cerebral, cardial, and peripheral vascular regions in different dosages. The aim of the symptomatic therapy is the improvement of the peripheral vascular disease symptoms, which could mean an improvement of the pain-free walking distance or the avoidance of an extremity-threatening ischaemic syndrome. The therapeutic range includes a structured exercise programme, conservative medical treatment, catheter procedures, and bypass surgery as well as amputation. The different procedures are mainly dependent on the general condition of the in many cases multimorbid patients, the clinical stage, the psychological burden and the angiologic status. There should be always an interdisciplinary discussion, which helps to find the right therapeutic decision. All the therapeutic activities should be seen under the guideline of an improvement in the quality of life. PMID- 8475640 TI - [Hypertension and diabetes mellitus]. AB - Numerous surveys have shown that in industrial countries diabetic subjects develop hypertension more frequently than non-diabetic persons. In fact, three typical hypertension forms in these patients can be discerned: essential, renal, and isolated systolic hypertension. In type 2-diabetes (NIDDM) hypertension can be seen in close association with obesity, glucose intolerance, lipid changes, and insulin resistance within the framework of the metabolic syndrome. The increased incidence of hypertension in type 1-diabetes (IDDM) is a result of development of diabetic nephropathy. In the elderly type 2-diabetics particularly frequently isolated systolic hypertension is present which reflects increased arterial stiffness and loss of vascular distensibility. In hypertension progression of both macrovascular disease and microangiopathy is increased whereby interaction of hyperglycemia and hypertension seems to be the main risk factor. In most hypertensive diabetic patients drugs will be necessary to lower blood pressure in a therapeutical range. There are several effective substances available which should be prescribed individually according to the needs and accompanying conditions in these patients. PMID- 8475641 TI - [Autonomic neuropathies in diabetes mellitus: diagnosis--therapy--risks]. AB - Autonomic neuropathy is a complication of diabetes which is observed in about 20% of all patients. This complication is often not adequately diagnosed. Neuropathy is a syndrome of various diseases that is classified according to the organs involved in the clinical picture. For the diagnosis of autonomic neuropathy besides the careful examination of the patient (metabolic and neurologic status, diabetic complications) a number of specific tests are available i.e. cardiovascular reflex tests and some other organ-specific tests. The review attempts to give an update of the presently used diagnostic approaches. As far as the therapy of all forms of neuropathy is concerned the careful control of blood glucose of the diabetic patient is still the only therapy which counteracts specifically the pathogenesis of autonomic neuropathy. There is however a number of drugs available which are useful for symptomatic therapy. Their effectiveness is discussed in this review. There is no doubt that diabetic autonomic neuropathies will have consequences for long-term prognosis and quality of life. PMID- 8475642 TI - Interrelations between electrical and biochemical processes in ischemic porcine livers at low temperature. AB - Recently it has been shown that during liver ischemia at 25 degrees C the presence of glycogen, by supporting glycolytic supply, not only retards ATP decay but also leads to a corresponding delay of the rise of the electrical impedance of the ischemic organ. A sudden rise of impedance during ischemia is supposed to indicate the closure of gap junctions. Although similar effects on energy state do exist at low temperature, the impact of glycogen on the electrical impedance under storage conditions has still to be evaluated. Therefore, in a model with protected porcine livers, we examined the intraischemic effects of a preischemic glucose and potassium feeding on impedance changes, lactate production and ATP content at a storing temperature of 5 degrees C. Impedance was measured both in the low frequency alpha- and the higher frequency beta-dispersion range. In addition, the same parameters were determined in a group of unprotected livers. In this group all animals had received glucose and potassium orally prior to ischemia. Whereas in case of preischemic glucose feeding the rise of impedance in the range of the beta-dispersion (e.g. 5kHz) roughly coincided with the exhaustion of ATP, the corresponding impedance changes in the protected group without a glucose premedication only occurred when glycolysis had already stopped and ATP had reached basal values for some hours. In contrast, in the alpha dispersion range the impedance changes in the latter group just began at the time when ATP became exhausted and lactate production ceased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475643 TI - [Computer systems in gastroenterologic endoscopy. An analysis of current availability on the Austrian market]. AB - Five systems for computerized documentation (ADAM-Fujinon, ENDOBASE-Olympus, MEDASYS-Pentax, MEPAS-Fritsch & Jirak, OPTAMED-Krotlinger) are compared in their different functions: configuration of system, software, communication, structure of program, user guidance, data-protection, data back-up, patient registration, preparation for examination, terminology setup, report generation, image filing, statistic, system adjustments, costs. This paper should be a help in buying a computer-aided system. All systems fulfil the three basic requirements for a computer-aided documentation in gastrointestinal endoscopy: database, image filing, report generation. Actually none of the programs can be favoured. Peculiarities, weakness and strength of the different programs are discussed. The principle of the scoring-method in choosing a system is explained. PMID- 8475644 TI - Inflamed pancreatic pseudocyst: optimization of pseudocyst fluid culture technique. AB - A serious complication of pancreatitis, inflamed pseudocyst is associated with considerable morbidity and relatively high mortality rate. In this study chronic pancreatic pseudocyst fluid was cultured by the conventional method as well as by a method of bedside inoculation of blood culture bottles with pseudocyst fluid. The conventional method grew bacteria in only 26 (65%) of 40 patients with chronic pancreatic pseudocyst, whereas the blood culture bottles grew bacteria in 38 (95%) patients (p < 0.001). The blood culture bottle method also resulted in more rapid detection of bacterial growth (p < 0.001). Inoculation of pseudocyst fluid into the blood culture method seems more sensitive than the conventional method in detecting inflamed pancreatic pseudocyst probably due to the low pseudocyst concentration of bacteria observed in this study. PMID- 8475645 TI - [Obstructive jaundice after granade splinter injury 49 years ago]. AB - The present case report describes a 69 year old man who was admitted because of severe pain in the right upper abdomen by condition after a Billroth II resection of the stomach and a obstructive icterus. The reason was a common bile duct stone with a central shell splinter. Due to purulent cholangitis with inflammatory stenosis of the distal ductus choledochus endoscopic removal of the stone was only successful in repeated attempts. PMID- 8475646 TI - [Blind loop of the large intestine--bypass enteropathy or diversion colitis?]. AB - Investigating three patients with longstanding diarrhoea, severe abdominal bloating and cramps revealed an exclusion of the right hemicolon in all patients and additionally of the terminal ileum in one of them. The anastomosis of the ileo-colic bypass, performed decades ago due to complicated appendicitis, was stenotic in two of them. Because a classical blind-loop-syndrome could not be proven, the functional disorder is described as a clinical entity characterized by signs of bypass-enteropathy and diversion-colitis. The importance of the radiological examination for diagnosis and therapy-planing is emphasized, because endoscopically and histologically Crohn's disease might be suspected. The surgical reintegration of the bowel into the orthograde continuity of the intestinal tract is recommended as the causative treatment. Symptoms disappear completely and patients win normal health even after some decades, because the morphological signs of inflammation are reversible and bowel function is not lost during the exclusion. PMID- 8475647 TI - [Physiologic regulation of gastric acid secretion]. AB - Physiological regulatory mechanisms of gastric acid secretion are the basis for all those studies which attempt to analyze the pathophysiological role of acid secretion. The major stimulus of parietal cell function is food intake which acts via activation of cephalic-vagal and gastric mechanisms. Cephalic phase of acid secretion is augmented predominantly by acetylcholine and gastrin while histamine is of major importance during the gastric phase. A contribution of neuropeptides located in the ex- and intrinsic nervous system such as enkephalin, beta endorphin, gastrin-releasing peptide and neuromedin C ist most likely, however, their exact physiological role remains to be determined especially in man. Following maximal acid secretion parietal cell function is turned down which is paralleled by the decrease of intragastric pH. The mechanisms responsible for this effect originate in the stomach and small intestine. In contrast to the stimulatory factors the physiologically relevant inhibitors of acid secretion are less well known. Hormones such as somatostatin, glucagon-like peptide-1 (7-36) NH2 and peptide YY are presumably of importance. The role of secretin, GIP, CCK and neurotensin is somewhat more controversial and remains to be examined in greater detail in humans. Especially the synergistic action of gastrointestinal hormones is virtually unknown. The increasing knowledge of the complex regulatory mechanisms in the stomach should result in new perspectives for the pathogenesis of peptic ulcer disease. PMID- 8475648 TI - [Nitric oxide (NO): a new, endogenous protective mechanism in gastrointestinal mucosa?]. PMID- 8475649 TI - [Use of sclerotherapy in patients with esophageal varices. Guidelines of the German Society of Digestive and Metabolic Diseases]. PMID- 8475650 TI - [Reproducibility of the signal-averaged, high-pass filtered electrocardiogram]. AB - In order to test the reproducibility of the signal-averaged electrocardiogram (SAECG) using Simson's method (high-pass filter cutoff frequency 25 Hz, orthogonal leads, recording of 133 s per lead), 121 patients were examined. In all patients, two signal-averaged ECGs were performed on the first day of the study immediately after each other, using identical electrode position. In a subgroup of 47 patients, the same procedure was repeated 3 days later. There was no difference between the mean values of conventionally calculated averaging parameters (heart rate, QRS-duration, root-mean-square voltage in the terminal 40 ms of the highly amplified and filtered QRS-complex [V40], the low amplitude signal duration under 40 microV in the terminal portion of the QRS-complex [LAS], total root-mean-square voltage of the QRS-complex), both with regard to immediate and short-term reproducibility. Thus, conventionally calculated averaging parameters are well reproducible. PMID- 8475651 TI - [Therapy of ventricular tachyarrhythmia with implantable cardioverters/defibrillators--mortality and complications using epicardial electrodes]. AB - Technical improvements of third generation implantable cardioverter defibrillators (ICD) like antitachycardia pacing modalities lead to an extended use of ICDs, not only in patients with aborted sudden cardiac death, but also in patients with hemodynamically tolerable ventricular tachycardia. In addition, anticipated results of current prospective studies might indicate the prophylactic use of ICDs in patients with high risk for sudden cardiac death, but without documented ventricular tachyarrhythmias. This report reviews mortality and complications associated with the ICDs with epicardial defibrillation leads. Mortality is separated in cardiac death, sudden cardiac, arrhythmogenic "not so sudden" cardiac death, and overall mortality. Pulmonary complications and infections are related to the underlying disease and the surgical procedure. Device- and lead-related complications, high defibrillation thresholds, pacemaker interactions, inappropriate shocks, arrhythmic effects, syncope, and psychosocial problems are reported, respectively. PMID- 8475652 TI - [Diagnostic value of intravascular ultrasound diagnosis in peripheral arteriosclerotic blood vessel changes]. AB - Intravascular ultrasound is an adjunct for the diagnosis of atherosclerotic peripheral vessels. In this in-vitro study, 69 segments of human peripheral arteries were fixed in formalin, examined with intravascular ultrasound and pathomorphologically evaluated. Sensitivity, specificity, both positive and negative predictive value and accuracy of intravascular ultrasound for the detection of irregular lumen contours, intraarterial structures and intimal thickening were determined for each of four quadrants. Sonographic features (echogeneity, homogeneity, shadowing of echoes) were compared to the architecture of lesions. Intravascular ultrasound detected regular (normal) lumen contours with high specificity (96.5%), a sensitivity of 65.0%, and an accuracy of 88.4%; intraluminal structures were detected with a sensitivity of 88.6%, a specificity of 97.8%, and an accuracy of 96.4%. Most atherosclerotic lesions could be localized with a sensitivity of 86.1%, a specificity of 99.1%, and an accuracy of 86.9%. Slight intimal thickening was detectable with a sensitivity of 85.9%, a specificity of 87.8%, and an accuracy of 86.2%. Comparison of sonographic features and the pathomorphological architecture of atherosclerotic lesions revealed that fibrous, atheromatous, and complex lesions without calcification did not show shadowing of echoes. The majority of fibrous or atheromatous lesions presented with homogeneous echoes; these lesions showed hypo-, hyper- and normodense echoes. The homogeneity of echoes did not help to identify the different components of combined atherosclerotic lesions. Thus, intravascular ultrasound is able to detect irregular lumen contours, intraluminal structures, and intimal thickening, but further sonographic criteria are needed to identify the architectural structure of combined lesions. PMID- 8475653 TI - [Detection of pacemaker electrode infection using intravascular ultrasound]. AB - The case of a 60-year-old man who developed fever 14 months after last implantation of a DDD pacemaker system is reported. Though staphylococcus epidermidis could be identified in several blood cultures, transthoracic and transesophageal echocardiograms and scintigraphy with antibodies to human leucocytes could not identify any focus of infection. The percutaneous intravascular and intracavitary ultrasound examination clearly demonstrated a vegetation within the subclavian vein, being attached to the ventricular lead; within that segment of the vein the atrial lead showed a small hyperdense structure. Further vegetations along the leads within the right atrium and ventricle could be ruled out. Subsequent removal of the pacemaker system caused resolution of the signs of inflammation. PMID- 8475654 TI - [Limitation of Doppler echocardiography in evaluation of aortic valve prostheses]]. AB - Doppler echocardiography has been widely used as a noninvasive method to evaluate valvular heart diseases. However, the diagnostic impact of Doppler echocardiography in the evaluation of prosthetic valves is discussed controversially. Reasons are, on one hand, the high variabilities of transvalvular gradients observed for normal prosthetic devices and, on the other hand, results of experimental in vitro studies demonstrating an impressive discrepancy between Doppler-echocardiographic and invasive measurements of the transvalvular gradients in prosthetic valves. In a prospective study, we evaluated 11 out of 335 patients after aortic valve replacement who demonstrated an elevated transvalvular gradient over the prosthetic valve. Eight patients had a St. Jude medical prosthesis (19-23 mm), two patients had a Medtronic Hall prosthesis, and one patient a Bjork-Shiley prosthesis. The maximal instantaneous gradient measured by Doppler-echocardiography was 74 +/- 15 mmHg, the mean gradient was 47 +/- 12 mmHg. The prosthetic orifice area calculated by the continuity equation using the left ventricular outflow tract diameter was 0.86 +/ 0.25 cm2, and that calculated by using the prosthetic ring diameter was 0.98 +/- 0.23 cm2. None of the patients had a severe aortic valve regurgitation. All patients were clinically asymptomatic. Transesophageal echocardiography and x-ray showed a normal prosthetic function. Angiographic examination performed in seven patients showed a peak-to-peak gradient of 26 +/- 9 mmHg, and demonstrated a marked discrepancy between Doppler-echocardiographic and invasive results. These results confirm the clinical limitations of Doppler echocardiography to distinguish between normal and disturbed prosthetic function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475655 TI - [Follow-up angiography after balloon dilatation of aortic isthmus stenoses in adults]. AB - Between May 1985 and April 1991, 30 patients (seven females and 23 males) 14 to 54 years old (median, 25 years) underwent balloon angioplasty for unoperated native (n = 26) or recurrent postoperative (n = 4) coarctation of the aorta. 28/30 patients had systemic hypertension (RR > 140/90 mmHg). Dilatation of the stenotic segment could be achieved in 28/30 patients. The residual pressure gradient was > 30 mmHg in six patients. In 2/4 patients with recurrent coarctation the balloon had ruptured, while dilatation was successful in the other two patients. The mean diameter of the stenotic segment increased from 5.8 +/- 2.7 mm to 11.9 +/- 2.5 mm and the peak pressure gradient decreased from 61 +/ 18 mmHg to 20 +/- 13 mmHg. Complications were a small hemorrhagic pleural effusion in one patient and a groin hematoma in another patient. Clinical follow up studies with retrograde catheterization of the aorta and angiography were performed in all 28 patients with dilated coarctation, 6 months to 6 years after the procedure, representing a total follow-up time of 72 (average, 2.6) patient years. Multiple follow-up studies (n = 2-4) were performed in 17/28 patients. In one patient the first angiogram revealed aneurysm formation while a small bulge was seen in two others. Intra-aortic pressure measurements revealed a peak gradient of < 30 mmHg in 24/28 patients with a mean of 14 +/- 10 mmHg. The blood pressure was normal in 23/28 patients. In the other five patients whose pressure gradients were 7, 30, 30, 35, and 60 mmHg moderate hypertension persisted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475656 TI - [Ambulatory blood pressure monitoring: significance of blood pressure variability for progression of heart hypertrophy]. AB - It is known that ambulatory blood-pressure monitoring gives a better prediction of target organ damage and prognosis than clinical blood pressure. Many studies have found a closer correlation for ambulatory blood pressure with left ventricular hypertrophy than clinical blood pressure. One question that is discussed controversely is whether the variability of blood pressure is also a determinant of target organ damage independent of the average level. In 52 patients with elevated casual blood pressure a 24-h ambulatory blood-pressure measurement (Space Labs 90202) was performed and left ventricular hypertrophy was evaluated by M-mode echocardiography. The following parameters of blood pressure variability were calculated from the profiles: the standard deviation of the mean value, the variation coefficient and the parameter of variability as proposed by Schachinger et al. Furthermore a Fourier analysis of the blood pressure data was performed to quantify blood pressure variability. We found no statistically significant correlation between blood pressure variability and left ventricular mass. However, systolic and diastolic blood pressure level showed a significant correlation with left ventricular hypertrophy (r = 0.45 and r = 0.49, p < 0.05). Thus, blood pressure variability as calculated from the ambulatory, non-invasive blood pressure monitoring is a poor predictor for secondary damage of the heart. PMID- 8475657 TI - [Diagnostic blood flow changes in the outflow tract of the left ventricle. A Doppler echocardiography study of arterial hypertension]. AB - In patients with arterial hypertension we analyzed left ventricular filling by pulsed wave (PW) Doppler in the left ventricular inflow and outflow tract (LVIT and LVOT resp.). Separately, we determined the optimal position of flow analysis within the LVOT. We investigated 20 normals (N) and 37 patients with hypertension present for more than 1 year and consistently above 160/95 mm Hg. There was no evidence of other diseases. Echocardiographic signs of left ventricular hypertrophy were present in 20 (H1) and absent in 17 patients (H2). The mean age was 50 years in all groups. We analyzed the velocities (V) and velocity time integrals (F) of the E- and A-waves, respectively, as well as their ratios [E wave (Ve,Fe), A-wave (Va,Fa), Ve/Va, Fe/Fa]. In the LVOT, we determined the end diastolic A*-wave (A-wave propagated from LVIT to LVOT) and the S-wave (systolic flow) [A*-wave (Va*,Fa*), S-wave (Vs,Fs), Va*/Vs, Fa*/Fs]. Altered flow patterns were detected more sensitively in the LVOT as compared to the LVIT, even without detectable hypertrophy: In the LVIT Va was significantly different in H1 as compared to N (0.62 +/- 0.15 m/s in H1 vs. 0.52 +/- 0.13 m/s in N; p < 0.05), while H2 and N were comparable. For Ve/Va the same results were obtained (0.97 +/ 0.33 in H1 vs. 1.29 +/- 0.40 in N; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475658 TI - [Consensus conference "Therapy of chronic heart insufficiency" inaugurated by the Munich Collegium for Therapy Research e.V. together with the German Society for Cardiovascular Research]. PMID- 8475659 TI - [The functional bases for the formation of sensory system interaction in ontogeny]. AB - The study of the mechanisms of the intersensory interaction and its development in the postnatal ontogenesis. The first proved evidence of participation of the intracortical inhibition mechanisms in the processes of heterosensory interaction on the cortical level. The study of formation in kittens of the heterosensory interaction on the neurons of the sensorimotor cortex area has established the correlation of the process with the interconnected maturing of the afferent entries to this cortex area, and the system of intracortical inhibition. Correlation was established between the time of development of the heterosensory interactions on neurons of the sensorimotor cortex area in ontogenesis and the age period when injury of the sensorimotor cortex destroys the ability of animals to produce a conditioned reflex to a complex heteromodal signal in case of inhibiting reactions to its components. Discussion of the problem of input of the cortical level to the process of heterosensory interaction in different phases of ontogenesis. PMID- 8475660 TI - [Evolutionary physiology and related sciences]. AB - A brief historical review of development of the evolutionary physiology as an independent discipline. Description of the problems and methodology of the evolutionary physiology in the historical perspective. Interrelation of the evolutionary physiology and the related physiological and biological disciplines, specific features of the evolutionary physiology as an independent research discipline. The proceedings of 10 workshops on the evolutionary physiology, and the national and international bibliographic publications on evolution of the organic world are used to demonstrate the structure and the changes in time of the thematic spectrum explored by the evolutionary physiology. PMID- 8475661 TI - [The problem of the stability of living systems and its evolutionary and morphofunctional bases]. AB - Stability of the living matter is not only a morphological problem, but also a physiological-behavioral problem. Analysis of data accumulated in this field is the topic of this study. Contradicting the existing assumptions, it has shown that the taxonomic stability is not a casuistic phenomenon, but an important independent and widespread law of evolution providing for conservation without modification of the structures and functions for sometimes tens and hundreds millions of years. This is the first publication of the concept of the material substratum of this phenomenon. The study has established that the stability of the orders of mammals persisting despite the variability of the somatic organs in many representatives, and conservation of this separation even in case of transition into the aquatic habitat are due to the regulating mechanism represented by the nervous system of animals and man. This is, in particular, reflected in the specific structural and physiological mechanisms on the subcortical and cortical levels (visual system and neocortex). The study questions the concept of the origin of mammals from a single root of primary insectivorous ancestors on the basis of the discovered cytoarchitectural differences in the visual system and neocortex, and also the most recent paleontological data. In view of that the author emphasizes the independent principle of cytoarchitectural organization of the above brain formations in each order, and their stable separation during the established paleontological history. This phenomenon is interpreted as a major evidence of the principle of stability in the evolution process. PMID- 8475662 TI - [The role of macrophages during the formation of regulatory connections between the immune, nervous and endocrine systems in the course of an immune response]. AB - The study explores the current understanding of the role of macrophages in the process of formation of the regulatory relations in the immune, nervous, and endocrine systems during the immune reactions. Discussion of the effects of the factors of macrophagal origin on the afferent section of the nervous system, on production of neuromediators of the sympathetic and parasympathetic sections of the vegetative nervous system, on production of neuropeptides and the functional activity of adrenals, and of the influence of the neuroendocrine system on the mononuclear phagocytes. Discussion of the role of macrophages in the intersystem regulation of the immune reaction. PMID- 8475663 TI - [Prof. B. P. Babkin, scientist and humanist of Russia and Canada]. PMID- 8475664 TI - [Rheumatism, Zipperlein and Pfotengram: therapy of rheumatic diseases in the course of time]. PMID- 8475665 TI - [Indications, problems and results of dynamic compression spondylodesis in rheumatic atlanto-axial instability]. AB - 37 patients suffering from rheumatoid atlanto-axial dislocation underwent operations with the dynamic compression spondylodesis from 1982 until 1990 at the Department of Neurosurgery of the University Hospital of Giessen and Essen. They were examined with an average of 2 years after the operation. The clinical and radiological follow up and the complications are reported. Because of the results the indication of the surgical treatment was modified. In the case of an extended peridental inflammatory pannus with osteolysis of the dens and vertical dislocation of the axis a occipito-cervical fusion is indicated. PMID- 8475667 TI - Combined interferon alfa-2a and cytosine arabinoside as first-line treatment for chronic myeloid leukemia. AB - Thirty patients with chronic myeloid leukemia in chronic phase and less than 1 year from diagnosis were treated with a combination of interferon alfa-2a (IFN) 9 million units daily continuously and intermittent low-dose cytosine arabinoside (Ara-C) 20 mg/m2 daily for 21 days every 42 days. The leukemia was controlled initially with hydroxyurea prior to commencing IFN and Ara-C. The treatment was continued for at least 12 months after which time nonresponders were withdrawn from the trial and responders continued on IFN alone. The median duration of follow-up is 14 months (range 10-53 months). Hematological response was assessed by clinical and laboratory parameters and cytogenetic response was assessed by regular bone marrow chromosome analysis. A complete hematological response occurred in 28/30 patients (93%). A complete cytogenetic response (no detectable Philadelphia chromosome-positive metaphases) was present on at least one occasion in 9/30 (30%), a partial cytogenetic response (between 1 and 34% Philadelphia chromosome-positive metaphases) in 7/30 (23%) and a minor response in 4/30 (13%), giving an overall cytogenetic response rate of 67%. Significant side effects included mucositis, nausea, cytopenia and depression. Side effects could be managed by dose reduction or temporary cessation and were tolerable in most patients, but in 1 patient this led to withdrawal from the trial due to severe depression. Two patients have transformed, 1 to acute lymphoblastic leukemia and 1 to accelerated phase. Two patients have died after exiting the study, both from complications of allogeneic bone marrow transplantation. In conclusion, these results are superior to the results using IFN alone and indicate the need for a randomized study. PMID- 8475666 TI - [Joint loose bodies in both upper ankle joints in neural muscular atrophy of the Charcot-Marie-Tooth-Hoffmann type (hereditary motor sensory neuropathy I)]. AB - A case is reported in which a patient with Charcot-Marie-Tooth-Hoffmann disease (HMSN I) complained about bilateral ankle pain, stiffness and swelling. Radiologically multiple loose bodies in both ankle joints were detectable. The etiology of loose bodies or secondary chondromatosis is still unclear. Different reasons are discussed. Regarding the case reported on here we discuss possible etiological connections and pathophysiological pathways that may explain influence of Charcot-Marie-Tooth-Hoffmann disease (hereditary motor sensory neuropathy I) on the development of loose bodies at both ankle joints. PMID- 8475669 TI - The role of all-trans-retinoic acid in the treatment of acute promyelocytic leukemia. AB - All-trans-retinoic acid (ATRA) has demonstrated in vivo and in vitro that it could differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA yields complete remission (CR) rates of approximately 90% in newly diagnosed and first relapsing APL, in APL resistant to one or two courses of chemotherapy, whereas patients in second and subsequent remissions often have only partial remissions. The use of ATRA in APL is associated with two major drawbacks: (1) the risk of rapidly rising leukocyte counts, leading to the 'retinoic acid syndrome' which may be fatal if the increase in leukocytes is not reversed and (2) almost universal relapse, if no intensive chemotherapy is administered after CR achievement. Preliminary results, however, suggest that ATRA followed by intensive chemotherapy has improved the outcome of newly diagnosed APL, by slightly increasing the CR rate but also by reducing the risk of relapse, as compared to chemotherapy alone. PMID- 8475668 TI - Interleukin-2 +/- lymphocytes as consolidative immunotherapy after autologous bone marrow transplantation for hematologic malignancies. AB - Patients who undergo autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies experience a high relapse rate. Therapy with interleukin 2 (IL-2) +/- lymphokine-activated killer (LAK) cells has induced clinical responses in some patients with advanced malignant lymphoma (ML) or acute myelogenous leukemia (AML). It is postulated that IL-2 +/- LAK cells represents a potentially non-cross-resistant therapeutic modality which might prevent or delay relapses if used as consolidative immunotherapy after ABMT, at a time of minimal residual disease. Therefore, we first studied the reconstitution of IL-2 responsive LAK precursor cells after ABMT and found them in the circulation as early as 3 weeks after ABMT. A phase Ib clinical trial was then performed which identified a tolerable IL-2 regimen which could be administered early after ABMT and which could induce immunomodulatory effects. We then initiated a clinical trial to determine the feasibility of generating and administering autologous LAK cells using this IL-2 regimen after ABMT for 16 patients with ML. The results show that IL-2+LAK therapy early after ABMT is feasible but is more toxic than IL 2 alone. Patients with AML on the phase I IL-2 trial and with ML on the IL-2+LAK protocol were evaluated for tumor status. Of 8 patients with AML in first relapse or at a later stage who underwent ABMT and received IL-2, 2 have relapsed, while 6 remain in complete remission 26+ to 40+ (median 28+) months after ABMT. Of 16 patients with ML considered at high risk for relapse who were treated with ABMT+IL-2+LAK, 5 have relapsed, while 11 remain in complete remission at 6+ to 21+ (median 10+) months after ABMT. The results in both trials are quite encouraging and appear to be better than those in nonrandomized historical controls at our institution. Prospectively randomized trials of IL-2 versus no IL 2 after ABMT in such patients are being initiated to assess definitively the effect, if any, on the relapse rate. PMID- 8475670 TI - Roferon-A in combination with Tigason in cutaneous T-cell lymphomas. AB - In cutaneous T-cell lymphomas (CTCL; mycosis fungoides and Sezary syndrome), the standard therapies tend to be effective but not curative. Single drug therapy with either interferon-alpha or retinoids shows a response rate of about 45%. In this article, we report the results obtained in the treatment of CTCL with a combined therapy. To date, four clinical studies have been carried out using a combination of low doses of interferon-alpha and retinoids for treatment in the early stages of CTCL. The mechanism of action of this combination therapy is unknown. PMID- 8475671 TI - Use of interferon alfa-2a to treat hematologic relapse of chronic myelogenous leukemia after bone marrow transplantation. AB - The use of recombinant human alpha interferon (IFN) to treat relapse of chronic myelogenous leukemia (CML) in chronic phase after bone marrow transplantation (BMT) was studied in a prospective trial. Relapse was defined as > 90% metaphases containing the Philadelphia chromosome (Ph) and hematologic abnormalities consistent with chronic phase CML. In the initial 18 patients, all received allogeneic marrow, 17 from a related donor, 1 from an unrelated donor. Only 1 patient received T-depleted marrow initially. Three patients had relapsed after second BMT. IFN was started at 3 x 10(6) IU/m2/day and escalated to the maximum tolerated dose or to a maximum of 6 x 10(6) IU/m2/day. Elevated white blood counts and platelet counts were controlled in 14 of 16 and 6 of 6 patients, respectively. Six patients (33%) have had a complete disappearance of the Ph (cytogenetic complete response) and 2 have had a partial response (cytogenetic partial response < 35% Ph+ metaphases but > 0%) on at least one sample. Six patients had no significant response after 9-12 months and 4 patients developed clinical accelerated phase or blast crisis after 3-6 months. IFN controlled the blood counts in 75% of patients. Of 4 patients with a sex marker, the Ph- population was of donor origin in 3 and of host origin in 1. Clonal cytogenetic abnormalities other than the Ph were present in 13 patients and did not predict for lack of response to IFN. IFN effectively produces hematologic control in the majority of patients and suppresses the Ph clone in up to one third. A trial of IFN treatment in an earlier stage of relapse is indicated. PMID- 8475672 TI - [On the 70th birthday of Prof. Dr. Rudolf Hofer]. PMID- 8475673 TI - [Beta-carotene, vitamin A and carrier proteins in thyroid diseases]. AB - The conversion of beta-carotene (provitamin A) to 2 molecules of vitamin A (retinol) is accelerated by thyroxine and hyperthyroidism, respectively. The characteristic yellow tint of the skin in hypothyroidism is due to hyper-beta carotenemia. Both in hyper- and hypothyroidism in a retinol deficiency has been observed in literature. In a series of 36 patients (16 hyper-, 8 hypo-, and 12 euthyroid) serum samples were analyzed for retinol and beta-carotene levels (high pressure liquid chromatography) as well as retinol binding protein (radial immune diffusion), prealbumin (nephelometry), and serum zinc values (atomic absorption spectrometry) were established. The beta-carotene serum level in the hypothyroid group (mean 1.1 microgram/ml) was significantly higher (p < 0.05) in relation to euthyroid controls (0.6 microgram/ml), the hyperthyroid group showed significantly lower values (0.3 microgram/ml). RBP and prealbumin concentrations were significantly lower (p < 0.05) in hyperthyroid as against eu- and hypothyroid patients. Surprisingly, in all 3 groups the retinol levels were not significantly different, although the hyperthyroid group was slightly lower (0.6 microgram/ml) than the mean value of 0.7 micrograms/ml in the other groups. A vitamin A and protein rich food, customary in Central Europe, seems to rule out any vitamin A deficiency both in hyper- and hypothyroidism. However, the beta carotene values are significantly higher in hypothyroidism, while in hyperthyroidism they were lower. As intrahepatic zinc content plays an important role in the synthesis of RBP and its secretion together with retinol, we also analyzed this component: The serum zinc levels in hyperthyroid patients were clearly higher (79.1 micrograms/dl) than in the hypothyroid group with 57 micrograms/dl (p < 0.05). PMID- 8475674 TI - [TBG isoforms in the course of hyperthyroidism]. AB - In 7 hyperthyroid patients on the one hand thyroxine-binding globulin (TBG) was determined by commercially available radioimmunoassay and on the other hand TBG isovariants were established by means of isoelectric focusing. For assessment blood samples were taken upon admittance to our hospital and 2 and 4 weeks thereafter, respectively, during antithyroid drug treatment. A comparative series of 10 euthyroid subjects were equally evaluated. Both groups showed no significant differences of TBG values at onset and in the course of antithyroid treatment. However, TBG isovariants showed significant decreases in anionic bands (pH 4.25 to 4.45) whereas a significant increase in cathodic bands (pH 4.55 to 4.65) at onset of treatment compared to the euthyroid control group could be observed. During the course of antithyroid treatment the values of TBG-isobands reversed reaching the pattern of normal group. In contrast to the recent research by Hashizume et al. we observed no reduction in TBG level in hyperthyroid patients although a significant shift in the TBG isovariants could be established. Due to the antithyroid treatment prescribed, the TBG isovariants finally reached the normal pattern of euthyroid controls. PMID- 8475675 TI - [Modification of maximal binding capacity and radio-T3/T4 distribution by carbamazepine and diclofenac]. AB - Marked changes in plasma thyroid function parameters due to medication have been described in literature. We, therefore, studied the influence of routine administration of carbamazepine and diclofenac upon the radio T3/T4 distribution to specific thyroid transport proteins as well as their maximal binding capacity (MBC) for T4. Both drugs have been found to lead to changes in T3 and T4 distribution but not to any influence upon MBC. The parameters of thyroid function mostly revealed reduced FT3 and FT4 values while bTSH was affected only by carbamazepine administration. PMID- 8475676 TI - [Initial experiences using SPECT cameras with multiple detector heads]. AB - User acceptance testing of newly installed gamma cameras is mandatory in order to verify manufacturers' specifications and to ensure optimal image quality. Acceptance test procedures are widely standardized today and are carried out following commonly accepted test protocols. Two new triple head gamma cameras have been installed during the last year at the Department of Nuclear Medicine of the Vienna University Hospital. For acceptance testing of these cameras a modified and expanded version of the commonly used test protocol for single head SPECT systems has been employed. Details of the tests that have been carried out and a comparison of the results obtained for both cameras are presented. Furthermore, some specific problems that are encountered during acceptance testing of multiple head systems are discussed. In particular it has been noted that some important tests of intrinsic camera parameters cannot be carried out, which makes a complete verification of vendors' specifications impossible. In spite of these problems the acceptance test system for multiple head cameras presented in this work was sufficient for establishing proper working conditions for clinical use. PMID- 8475677 TI - [Iodine supply and struma in Austria]. AB - Austria is an iodine deficient area as are most parts of Europe. Goiters were always a natural phenomenon. In 1924 goiter prevalence in school children was 45 to 47% and a first attempt was made with iodized salt. This iodized salt (5 mg NaI/kg salt) was not used widely and goiter prevalence remained unchanged for decades. Therefore, in 1963, salt iodized with 10 mg KI/kg was introduced by law in a semi-mandatory way: Non-iodized salt was allowed to be sold only by special request. Consequently, in 1982, 68% of the total salt sold was iodized salt, goiter prevalence dropped to 1.5% in first graders, hypothyroidism in newborns was 1:4,600 and cretinism disappeared. However, in 18 years old females, goiter prevalence was still 13%, and in adults up to 30%. Investigations in various regions of Austria showed that iodine supplementation was insufficient with a mean urinary excretion of 42 to 75 micrograms I/g Cr. Therefore the Austrian Society of Nuclear Medicine (ONG) demanded the raise of the iodine content of salt to 20 mg KI/kg. Finally, in 1990 a new law was issued by the Government following this proposal. In 1992, investigations were done in various regions of Austria demonstrating a normalized iodine excretion of 129 to 177 micrograms I/g Cr. Further prospective and retrospective studies will be done by the ONG. PMID- 8475678 TI - [Diagnosis of lung embolism]. AB - Although lung scanning has been performed for nearly 3 decades, the diagnosis of pulmonary embolism (PE) still remains problematic. Only about 20% of all autopsy proven cases of PE have been diagnosed during life time. Biello, and later authors of the PIOPED study defined 3 probability levels for perfusion/ventilation (inhalation) scan interpretation in comparison with pulmonary angiography: High probability (about 90% PE), indeterminate (27 to 50% PE) and low probability (about 5% PE). If the scan results are in the high and low probability group, the diagnostic procedure can be stopped. However, in the indeterminate group including 36 to 52% of all patients, diagnosis should be confirmed by pulmonary angiography. This diagnostic procedure is not well accepted by clinicians, only 0 to 15% of all patients suspected of PE undergo angiography. The diagnostic problem is more complicated due to the large amount of clinically silent PE (39 to 59% of all PE). The inclusion of the diagnosis of thrombosis ("thromboembolism") into the diagnosis of PE increases the pre-test probability for PE to 55 to 60% (= prevalence of PE in patients with deep vein thrombosis). According to Bayes' theorem, the post test probability then exceeds 95%. Without considering thrombosis, the pre-test probability is very low and therefore the post-test probability of a pathologic scan is markedly lower than 50%. PMID- 8475679 TI - [Primary and follow-up studies of patients with carcinoid metastases using indium 111 octreotide--rational use of Sandostatin]. AB - Carcinoids may express Somatostatin receptors. Therefore, a Somatostatin analogue, In-111 Octreotide (OctreoScan), was used for their demonstration. A total of 6 patients who presented with radiologically verified carcinoid metastases was examined. In order to control tumor progress, 4 of these patients were reexamined within a period of 3 to 11 months. All of the radiological findings were confirmed scintigraphically, except some small retroperitoneally located lymph nodes. The follow-up examinations of 2 patients revealed additional metastases by scintigraphy only. There were no false positive results. The results of OctreoScan scintigraphy may be used for predicting the success of receptor-specific therapies and therefore, permit the rational and efficient application of Sandostatin. PMID- 8475680 TI - [Immunoscintigraphy for detection of inflammatory perioperative foci]. AB - The aim of our study was to evaluate the clinical usefulness of a monoclonal antibody (MAB; BW 250/183; Behringwerke, Germany) in patients with suspected perioperative septic foci. The MAB is directed against the nonspecific crossreacting antigen (NCA 95) which has been found on the surface of human neutrophil granulocytes and which represents a murine immunoglobulin isotype of IgG1. Immunoscintigraphy was performed by labelling the MAB with 740 MBq (20mCi) Tc-99m. Data acquisition followed 4 and 18 to 24 hours after administration by a digital Anger camera (APEX 409A, Elscint). 53 patients were investigated (31 female, 22 male; average age 39 years), 4 patients were twice, 1 patient was 3 times evaluated, which results in a total of 59 studies. 45 patients experienced operation within 12 hours after our investigation, which resulted in 36 true positive, 5 true negative, 3 false negative, and 1 false positive findings. This means a sensitivity of 92%, and specificity of 83%. Immunoscintigraphy with granulocyte antibodies can be performed at any time, the preparation of the radiopharmaceutical is simple, the image quality is high; the obtained information concerning localization and size of perioperative septic infections permits the determination of the optimal point of time for surgical intervention. The accumulation of activity was visible as early as 4 hours post application. SPECT would enhance the diagnostic accuracy, but this technique cannot be applied in all such patients. PMID- 8475682 TI - [Iodine content of thyroid tissue in the Styrian population]. AB - The iodine concentration was determined in 89 thyroid tissue samples of post mortem examination material of thyroid healthy persons in dependency to the age. Before the 22nd week little iodine is stored in the fetal thyroid gland (median and range: 24 micrograms/g wet weight [0 to 27 micrograms/g]). From the 23rd week on the concentration is significantly higher (p = 0.004). There is a further increase of iodine concentration in the first 6 months of life, with a median concentration of 171 micrograms/g (75 to 808 micrograms/g). With a median of 599 micrograms/g (464 to 699 micrograms/g) the iodine concentration in the second year of life is comparable with that of adults (640 micrograms/g [218 to 2772 micrograms/g]). From the 60th year of life the median concentration is 462 micrograms/g (155 to 2100 micrograms/g), but this decrease is not statistically significant. Additionally the iodine concentration was determined in 7 topographically defined regions of 28 thyroid glands. The median iodine concentration did not differ in the 7 regions, but the iodine content in one and the same thyroid gland differed from region to region. Therefore in the healthy thyroid gland no regions exist, which have generally stored less iodine than others. However, no conclusion can be drawn from the iodine concentration of one biopsy to the whole iodine concentration of the organ. PMID- 8475681 TI - [Radiosynovectomy with dysprosium-165 iron hydroxide]. AB - Treatment of chronic rheumatoid synovitis (RS) is directed to control the inflammatory process causing pain and disability. Radiation synovectomy is suggested to be an alternative to surgical treatment, but its clinical use has been restricted because of significant leakage (> 10%) associated with the use of the standard radionuclide 90-Yttrium (used as 90-Yttrium silicate colloid) and because of its long physical half-life of 64 hours prolonging the patients' stay in the hospital. 165-Dysprosium possesses promising nuclear properties for the treatment of patients suffering from RS. The maximum soft tissue penetration of its beta-particles is 5.7 mm which is the range being necessary to penetrate the inflamed synovia. Using as carrier ferric hydroxide macroaggregates (DFH) 165-Dy is expected to minimize the cumulative radiation dose to non-target organs by its very low leakage. Animal studies were performed in 13 rats and 6 rabbits to obtain the rationale and safety data for its clinical evaluation. These studies revealed that 98.2 +/- 0.6% of the injected dose remained in the joint with a nontarget organ uptake of less than 0.1%. Clinical results were obtained from 8 patients with rheumatoid arthritis. 24 hours after injection scintigraphy was performed over the treated joint and the liver region revealing no detectable leakage of the injected activity from the joint. Blood pool activity was also assessed revealing a leakage of 0.02% of the dose injected in the knee 24 hours after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475683 TI - [Combined therapy with cyclosporin A and cortisone in endocrine Basedow endocrine orbitopathy: successful use in compressive optic neuropathy]. AB - This study reports our experience with a combined treatment with cyclosporin A (Cy A) and cortisone in patients with Graves' ophthalmopathy (GO), all of whom had compressive optic nerve disease (CON). The therapy was performed in 8 patients (6 females, age range: 40 to 76 years) with normal liver and kidney function and classical Graves' disease, except for 1 male, who had normal thyroid function and no detectable thyroid antibodies. 5 patients were euthyroid on methimazole, 2 patients were off thyrostatic treatment for 5 and 2 years. 3 patients have had high-dose cortisone (100 mg/die) treatment for GO before the study. Visual field defects were reported by the patients 1 week before start of therapy and evaluated by computerized visual field measurements (CVFM). The treatment consisted of Cy A in a dose which aimed at through levels between 100 and 300 ng/ml (RIA method) for 2 to 6 months and of methylprednisolone in a starting dose of 1 mg/kg body weight, tapered gradually to a maintenance dose of 10 mg/day for 6 to 12 months. CON disappeared completely in all patients. The thickening of affected eye muscles decreased in 5 patients, disappeared in 1 and remained unchanged in 2 patients. The shortest period for a measurable effect (either by echography or by CVFM, performed every week the first month and then every 3 months) was 1 week; the longest 1 month. The follow-up of the patients (range 6 months to 2.5 years) showed a relapse only in 1 patient. 2 patients were lost to follow-up 1 year after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475684 TI - Sleep in Parkinson's disease. AB - Two major sources of dissatisfaction with the quality of life among Parkinsonian patients are the "locomotor disability" and the "nature of their sleep". The main focus of research was directed towards the locomotor disability, but in the last two decades some progress has been made towards the understanding of sleep in PD patients. Sleep in Parkinson's disease is light and fragmented due to an increased skeletal muscle activity, disturbed breathing, impaired biological rhythm and REM-nonREM variations of the dopaminergic receptor sensitivity. PMID- 8475685 TI - Assessment of response fluctuations in Parkinson's disease by ambulatory wrist activity monitoring. AB - The aim of this study was to examine the influence of response fluctuations with dyskinesia on the 24-h motor activity pattern and measures of diurnal and nocturnal activity and immobility. Motor activity was recorded during 5 successive days in 5 patients with advanced Parkinson's disease (PD) suffering from severe response fluctuations with dyskinesia, as well as in 10 PD patients with a stable levodopa response and 10 healthy subjects. The 24-h motor activity pattern of the patients with response fluctuations provides insight into the relationship between the therapeutic regimen and 1) the frequency and duration of "on" and "off" periods, 2) the severity of the dyskinesias, and 3) the degree of sleep disruption. In accordance with the severity of their motor fluctuations, patients with response fluctuations showed a large intra- and interindividual variability of diurnal motor activity measures. Overall, the nocturnal motor activity measures in the patients with response fluctuations indicated a severely disturbed sleep when compared with the two control groups. Factors as simplicity and the potential to record unrestrained motor activity for several days continuously in all settings, make activity monitoring a welcomed acquisition in the assessment of response fluctuations in PD. PMID- 8475687 TI - Rising mortality from motor neurone disease: an explanation. AB - There is considerable debate about the increasing mortality from motor neurone disease (MND). However, examination of the relationship between increased life expectancy (through decreased general mortality) and increased mortality in both England and Wales and the United States indicates a close association between the two variables. Using a statistical model, defined sub-populations susceptible to MND can be identified in both countries. The size of such a sub-population has been estimated from the 1989 mortality data to be approximately 160,000 people in England and Wales. The proportion of this sub-population dying from MND has increased over the last 30 years, rather than, as previously, dying at an earlier age from other conditions. On this basis, deaths from MND are expected to increase by a further 20% in this sub-population between 1991-2021 because of continuing changes in life expectancy. MND is a condition made increasingly visible in mortality statistics through decreased general mortality, rather than one in which the underlying population at risk has substantially changed. Aetiological extrapolations from the data indicate that susceptibility to the disease is acquired early in life, and that it is unlikely, given the relative stability of the underlying sub-population, that either changed environmental circumstances or artifactual factors can account in themselves for the rise in mortality. PMID- 8475686 TI - Paired choice reaction tasks in patients with Parkinson's disease. AB - Simple reaction, single choice reaction, and paired choice reaction tasks were examined in 11 patients with Parkinson's disease (PD) and 12 controls. Subjects were given an auditory go/no-go signal in the single choice reaction task, and paired visual and auditory go/no-go signals in the paired choice reaction task. The response following the auditory go/no-go signal was analyzed. The reaction and movement times were prolonged in patients with PD. Differences between simple and choice reaction times in PD patients did not differ from those in control subjects. The difference in movement time between simple and paired choice reaction tasks in PD patients was longer than that in control subjects, although the difference between simple and single choice reaction tasks was not significant between PD and control subjects. Sequential choices of visual and auditory stimulation may disturb the motor activity in PD patients. PMID- 8475688 TI - IgG subclass deficiency in amyotrophic lateral sclerosis. AB - In order to get to clues about T-cell independent versus T-cell dependent immune mechanism in ALS, we measured IgG subclasses in 25 ALS-patients: 16 patients had deficiency of T-cell dependent expressed IgG1 or IgG3 or both with essentially normal levels of T-cell independent expressed IgG2 and IgG4. Ten of these patients had no prior treatment and five of these 10 had normal total IgG. Six patients had some immunosuppressive treatment before measurements of subclasses were done and all of them had deficiency of total IgG. Eight of 14 patients who underwent a d-xylose breath test, had evidence of small bowel overgrowth, which was confirmed by cultures of duodenal aspirate. IgG1 and IgG3 are T-cell dependent antibodies against protein antigens with close linkage on chromosome 14. The findings suggest a defect in the IgG subclass expression in ALS. PMID- 8475689 TI - Increased water self-diffusion in chronic plaques and in apparently normal white matter in patients with multiple sclerosis. AB - A new method for measurement of water self-diffusion compensating for zeroth and first order movements was used to study the apparent diffusion coefficient (ADC) in 15 patients with chronic multiple sclerosis (MS) and in two patients with acute MS. Ten healthy volunteers served as controls. A significantly higher ADC was found within chronic plaques compared to the apparently normal white matter of the chronic patients. The ADC was higher in the acute plaques compared to the chronic plaques. The ADC in apparently normal white matter of the chronic patients were significantly higher than in white matter of healthy volunteers. We hypothesize that an increase of the ADC in plaques may be related to an increase in the extracellular space due to oedema and demyelination. The increased ADC in apparently normal white matter suggests that there may be a change in the composition of the white matter of chronic MS patients, perhaps related to oedema and expanded extracellular space. PMID- 8475690 TI - Clinical neurological findings among metal degreasers exposed to chlorinated solvents. AB - Among industrial solvents in present use trichloroethylene belongs to those which have been the concern of most neurological and occupational investigations since the beginning of this century. Reports on a broad spectrum of neurotoxicity are however mostly based on case-studies and accidental circumstances. The object of this study was to examine clinical neurological manifestations after long-term exposure to degreasing solvents, mainly trichloroethylene. The population was 99 metal degreasers, the design a historical cohort study. The most marked finding was a highly significant dose-response relation between solvent exposure and motor dyscoordination--a finding that was retained after multivariate control of relevant confounders. Vibration thresholds increased by solvent exposure at bivariate level, but the multivariate analysis showed that age was explaining most of the increase. No significant cranial nerve dysfunction was found. PMID- 8475691 TI - Clinical outcome and brain MRI four years after carbon monoxide intoxication. AB - Brain damage from carbon monoxide intoxication has not been extensively studied with magnetic resonance imaging. We report the clinical outcome and brain magnetic resonance imaging in three individuals simultaneously exposed to toxic levels of carbon monoxide four years previously. Lesions are seen in multiple locations and do not correlate well with the clinical condition. PMID- 8475692 TI - Minor structural brain changes in young drug abusers. A magnetic resonance study. AB - Twenty-three drug abusers and seventeen controls underwent clinical neurological examinations and magnetic resonance imaging (MRI) of the brain. The drug abuse encompassed cannabis, inhalants, opiates, psychedelics, amphetamines, and cocaine but not necessarily all drugs in all persons. The drug abuse was always combined with heavy alcohol consumption. One drug abuser had abnormal neurological findings which consisted of lower limb ataxia and 3 others had mild imbalance. MRI examinations did not show differences in width of the third, fourth or lateral ventricles nor the diameter of the cerebral aqueduct but the drug abusers had significantly smaller vermes cerebelli compared to controls. White matter changes also occurred more often in the drug abuser group. These findings are not consistent with known side-effects of the narcotic drugs but more probably a result of very high alcohol consumptions in parallel with drug abuse. Alcohol is clearly a much more potent brain toxic agent than are the most commonly abused narcotic drugs. PMID- 8475693 TI - Importance of cerebral pan-angiography for detection of multiple aneurysms in patients with aneurysmal subarachnoid haemorrhage. AB - In the Danish Aneurysm Study 948 patients had a ruptured intracranial aneurysm (RA) revealed by cerebral angiography. Unilateral carotid angiography (UCA) with or without vertebral angiography (VA) demonstrated the RA in 206 patients, and 16 (7.8%) unruptured aneurysms (UA) were disclosed by UCA and 1 UA by VA. In 740 patients with at least bilateral carotid angiography (BCA) 164 UA (22.2%) were disclosed by BCA and 10 by VA. I.e. the number of UA demonstrated in patients with RA is not only doubled by BCA compared to ipsilateral UCA, but tripled demonstrating that an additional UA is more likely situated on the opposite side of the RA. Pan-angiography (or at least BCA) is therefore recommended in patients with RA. PMID- 8475694 TI - Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment. AB - Efficacy and tolerability of the new antiepileptic drug oxcarbazepine, was evaluated in a retrospective multicentre study. The records of all 947 epilepsy patients treated with oxcarbazepine in the eight participating centres from 1981 through 1990 were examined. The median daily dose of oxcarbazepine was 30 mg/kg in children, 18 mg/kg in adults, and 15 mg/kg in elderly patients, given b.i.d. or t.i.d. The mean plasma levels of the main active metabolite of oxcarbazepine was 88, 79, and 68 mumol/l in children, adults, and elderly, respectively. In patients shifted to oxcarbazepine treatment, seizure frequency was unchanged in 51-66%, 32-48% had a decrease, and 1-10% an increase in seizure frequency, considering the individual seizure types separately. Adverse events were reported in one third of patients, most frequently affecting the CNS (dizziness: 6%; sedation: 6%; fatigue: 6%). Rash was reported in 6% of patients, half of these patients had previously had an allergic reaction to carbamazepine. Hyponatremia was found in about a quarter of the patients from whom data were available. No congenital malformations were seen in nine live-born, first trimester oxcarbazepine-exposed children. PMID- 8475695 TI - The stereotactic biopsy diagnosis of focal intracerebral lesions in AIDS patients. AB - Focal intracerebral lesions were biopsied stereotactically in 23 adult HIV infected patients, the main indication for which was the failure to respond to anti-toxoplasma treatment. A cerebral disease was the initial or main complaint in 19 of them. In 22 of 25 stereotactic approaches, a clear-cut morphological diagnosis could be established (9 primary brain lymphoma, 7 necrotizing toxoplasma encephalitis, 5 progressive multifocal leukoencephalopathy, 1 HIV encephalitis, 3 unspecific tissue changes). In 7 of 8 deceased patients, autopsy confirmed the bioptical diagnosis. The high diagnostic yield was related to the strategy of the stereotactic method and the sample size (3 to 4 consecutive samples along the stereotactic track including the marginal zones, 1 cm long tissue cylinders). Formalin fixation and paraffin embedding of the samples provide the possibility of serial sections and special stainings (immunohistochemistry, in-situ hybridization) and kill the HIV. Stereotactic brain biopsy is a highly accurate diagnostic tool to ascertain the nature of focal intracerebral lesions in selected AIDS patients. PMID- 8475696 TI - Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome. AB - Water metabolism and the responses of the neurohypophysis to changes in plasma osmolality during the water loading and water deprivation tests were studied in nine patients with postviral fatigue syndrome (PVFS) and eight age and six matched healthy control subjects. Secretion of arginine-vasopressin (AVP) was erratic in these patients as shown by lack of correlation between serum and urine osmolality and the corresponding plasma AVP levels. Patients with PVFS had significantly low baseline arginine-vasopressin levels when compared with healthy subjects. Patients with PVFS as a group also showed evidence of increased total body water content. These results may be indicative of hypothalamic dysfunction in patients with PVFS. PMID- 8475697 TI - Gait disorders of multi-infarct dementia. CT and clinical correlation. AB - Twenty-five patients with various types of gait disorders of multi-infarct dementia (MID) were reported. The types of gait disorders consisted of lower body parkinsonism (LBP) plus ataxia (6 patients), LBP plus apraxia (5 patients), and a combination of LBP plus ataxia and apraxia (14 patients). Hypertension occurred in 23 (92%) of the 25 patients. Nevertheless, individual stroke risk factors and the locations of infarcts were not significantly different between the subgroups. Ventriculomegaly and "leuko-araiosis" as demonstrated by computed tomography occurred in more than 80% of patients in each subgroup. Atrophy of the superior vermis was seen in 16 (80%) of 20 patients with ataxia as compared to 2 (40%) of the 5 patients without ataxia (p < 0.005). These data suggest that LBP and apraxia of MID were probably determined by the presence of ventriculomegaly or leuko-araiosis or both, and the presence of ataxic component of gait disorder most probably indicates the presence of vermian atrophy. PMID- 8475698 TI - Localized cranial hyperostosis of meningiomas: a result of neoplastic enzymatic activity? AB - Cranial hyperostosis is a common secondary manifestation of intracranial meningiomas. This may occur with or without neoplastic invasion, apart or even remote from the growth. Alkaline phosphatase (AP) is one of many enzymes produced by meningiomas and is known to possess indirect ossifying properties. Meningiomatous cranial hyperostosis could possibly be mediated by a humoral mechanism. This hypothesis was tested using chemical and histochemical determination of the occurrence of the enzyme in a series of hyperostosing and non-hyperostosing meningiomas. In the hyperostosing type the content of AP was in average more than three times as high as in the non-hyperostosing type. The results thus are in favour of the induction hypothesis. PMID- 8475699 TI - Suprascapular neuropathy restricted to the infraspinatus muscle in volleyball players. AB - Six volleyball players developed weakness and atrophy of the infraspinatus muscle on the dominant side. Electromyography (EMG) disclosed denervation and motor unit loss restricted to the infraspinatus muscle, the supraspinatus and other shoulder muscles remaining normal. Infraspinatus neuropathy may occur as a professional hazard in volleyball players. A lesion of the suprascapular nerve at the spinoglenoid notch is implied. PMID- 8475700 TI - The role of signal transduction in the delayed necrosis of the hippocampal CA1 pyramidal cells following transient ischemia. AB - A short period of cerebral ischemia leads to necrosis of the hippocampal CA1 pyramidal cells. Until recently no mechanisms contributing to this selective vulnerability were known. During the last decade an increasing amount of research has been concentrated on identifying signs of disturbed signal transduction in these neurons after ischemia. The present thesis is a review of these studies with some emphasis on my own contributions to the field. Gerbil and rat models of transient global ischemia are the most frequently employed. In order to produce the selective necrosis the main arteries to the brain are occluded for 5-20 minutes. In the rat it is often also necessary to lower the blood pressure. It takes 2-7 days of recirculation before the CA1 pyramidal cells become necrotic. The studies show that the necrosis can be attenuated or aggravated by drugs acting as inhibitors or enhancers of signal transduction--also if administered shortly after ischemia. The necrosis can be similarly influenced by lesions of excitatory or inhibitory afferent neurons. The protective effect of the lesion however, can be due to the lesion-induced decrease in metabolism. During ischemia there is an increase in the extracellular concentration of several excitatory and inhibitory neurotransmitters as well as in intracellular second messengers. Some of the latter also show an increase during recirculation. In vitro autoradiographic studies of receptor proteins show either unchanged or diffusely distributed downregulation of the ligand binding to the various extra- and intracellular receptor proteins following ischemia and early recirculation. A second decrease is seen in the CA1 at the time of and probably secondary to the necrosis. The IP3 receptor decrease appears during the first minutes of recirculation and lasts for up to 14 days. The protective lesion of the excitatory afferents from CA3 also leads to a decrease in IP3 binding. The changes in receptor regulation are not accompanied by increased postischemic electrophysiological activity in the CA1. In vivo autoradiographic mapping of the regional cerebral metabolic rate of glucose show increased metabolism in the CA1 during the first hour of recirculation compared to the rest of the brain were it is depressed. This relative hypermetabolism is not seen if the CA1 has been deprived of its primary source of excitatory afferents. A later secondary increase seen in the more or less necrotic CA1 pyramidal cell layer is probably due to macrophage activity. In situ hybridization and immunohistochemical studies on the expression of c-fos mRNA and protein respectively has been used to depict neurons with increased activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8475701 TI - Visual functions in a Swedish population of dyslexic and normally reading children. AB - Eighty-six 9-year old dyslexic children were carefully matched to controls with regard to age, sex, class in school, and intelligence and thorough visual functions tests and eye examinations were performed. As a group the dyslexic pupils exhibited a lower distance as well as near visual acuity both with monocular and binocular viewing. Furthermore, the dyslexic pupils had a lower contrast sensitivity at the lower and higher spatial frequencies. These differences were all statistically significant. However, no statistically significant differences between the two groups could be observed regarding refractive errors or contrast sensitivity in the middle spatial frequency range. Although some eyes were amblyopic, any severe eye anomalies or diseases were not found in any of the investigated children. PMID- 8475702 TI - Oculomotor functions in a Swedish population of dyslexic and normally reading children. AB - Eighty-six nine-year-old dyslexic children were matched to control children with regard to age, sex, class in school, and intelligence. Orthoptic and eye movement analysis were performed on all children. It was concluded that the dyslexic pupils did not differ significantly from control children in terms of strabismus, accommodation, stereo acuity, vergence function or ocular dominance. Eye movement recordings did not show any qualitative differences between the groups in vergence dynamics during synoptophore investigations. PMID- 8475703 TI - Tonometry in the general practice setting (I): Tono-Pen compared to Goldman applanation tonometry. AB - Intraocular pressure was measured in 132 consecutive patients over the age of 20 in a general practice with two general practitioners (GP). Tono-Pen tonometry was compared to Goldmann applantation tonometry in a masked, randomized design. Also, agreement between Tono-Pen measurements by the GPs and the ophthalmologist was estimated. Both mean difference between Tono-Pen and Goldmann applantation measurements and mean differences between Tono-Pen readings made by GPs and ophthalmologist were less than 1 mmHg. Ninety-five percent limits of agreement between the two methods were approximately -4.5 mmHg and 5.5 mmHg, and between observers approximately -4 mmHg and 5 mmHg. The Tono-Pen was agreeable both to patients and physicians. The GPs made as accurate measurements as the ophthalmologist. The wide limits of agreement are clinically much more important than the small differences between means. Random variation was much greater than systematic variation. Wide limits of agreement will apply to all known methods of clinical tonometry. PMID- 8475704 TI - Tonometry in the general practice setting (II): Which cut-off point for referral- for which patients? AB - A tonometry study comparing Tono-Pen with Goldmann applanation tonometry in a general practice setting revealed four cases of ocular hypertension in 132 patients. Two of the 4 patients required further ophthalmological care after referral. None of these patients, but 4 patients with no ocular hypertension, would have been referred for follow-up if referral had been made on the basis of the single reading made by the general practitioner. Tonometry readings are subject to considerable random variation, and the implications for a cut-off policy in general practice is discussed. Associations between ocular hypertension and known risk factors are weak and offer limited help in selecting asymptomatic patients for measurement. Systematic screening should not be a routine. The cut off point should be kept low to avoid false reassurance of glaucoma patients, possibly as low as 17 mmHg. Multiple measurements may limit the number of referrals if the readings remain low. PMID- 8475705 TI - Elevated serum sialic acid in idiopathic acute iridocyclitis. AB - We measured the serum levels of sialic acid in 12 patients with idiopathic acute iridocyclitis and 18 normal controls. Sialic acid levels were significantly elevated in the patients with idiopathic acute iridocyclitis. Since animal studies have shown that intraocular inflammation alone cannot elevate serum level of sialic acid, the result of our study suggest that idiopathic acute iridocyclitis may be a multiorgan disease with systemic effects. PMID- 8475706 TI - Optic disc diameter influences the ability to detect glaucomatous disc damage. AB - We studied the influence of optic disc diameter on the diagnostic power of subjective disc evaluation of glaucoma. One hundred and thirteen colour disc photographs of 91 patients with primary open angle glaucoma and 174 photographs of 89 randomly selected normal subjects were studied. Five ophthalmologists independently classified all eyes as glaucomatous or normal by disc appearance using a masked forced choice design. Sensitivities and specificities varied strongly as a function of disc diameter. Overall sensitivity for recognizing glaucoma by disc inspection was 58% in small discs, 72% in the middle group and 85% in the group of large discs. These differences were significant, and the odds of recognizing a glaucomatous disc as such increased by a factor of 2.07 between each group. Overall specificity was 99.6% in small discs, 95% in the middle group, and 79% in large normal discs. Thus, larger discs were more likely to be classified as glaucomatous whether they were glaucomatous or not, while small discs were more likely to be classified as normal. PMID- 8475707 TI - A case of ocular brucellosis: importance of vitreous specimen. AB - Brucellosis is a rare cause of uveitis, seen more often in developing countries. We report a case of ocular brucellosis, where diagnosis was confirmed with a high Brucella agglutination titer in the vitreous specimen. The case was treated by pars plana vitrectomy and antibiotics. We believe that a vitreous specimen is very important in the diagnosis of ocular brucellosis. PMID- 8475708 TI - Mikulicz syndrome and disease: 2 case reports highlighting the difference. AB - We present 2 case reports highlighting the essential differences between Mikulicz syndrome and Mukulicz disease. A review of the literature appears to show some confusion over the terminology and we therefore also present an historical account of the evolution of the two terms and review their relative merits and relationship with other disorders. In conclusion, we would not advocate the use of the term Mikulicz syndrome and suggest that Mikulicz disease be replaced by the title 'Benign Lymphoepithelial Lesion'. PMID- 8475709 TI - The prevalence of diabetic retinopathy in northwest Spain. An epidemiological study of diabetic retinopathy in Galicia. I. AB - The prevalence of retinopathy was studied in a group of 1179 diabetic patients attending 11 diabetologic centres in Gallica (Northwest of Spain). The age of the patients was 61.7 +/- 13.8 years, 43.8% were males and 56.2% females. The patients had had diabetes from 8.4 +/- 7.5 years, 30.4% were being treated with insulin, and 69.6% with oral antihyperglycaemics. 16.1% were aged under 40 years at onset as against 83.9% aged over 40 years. The prevalence of retinopathy was 44.7, in the whole group. Stepwise multiple regression analysis identified treatment time since onset and age at onset as the factors affecting prevalence, which was 61.8% in the insulin-treated subgroup vs 37% among those treated with oral antihyperglycaemics (p < 0.0001). The prevalence of proliferative diabetic retinopathy was 5.8% in the whole group. PMID- 8475710 TI - The postnatal development of the oscillatory potentials of the electroretinogram V. Relation to the double peaked a-wave. AB - The postnatal development of the double peaked a-wave and its relation to the oscillatory potentials of the rat electroretinogram was studied. The split a-wave appeared one day later than the first oscillatory activity. The appearance and maturation of the positivity between the two a-waves (a-hump) was found to be similar to that of the first oscillatory potential, and the development of the second a-wave showed similarities to that of the second oscillatory potential. Thus, we conclude that the double peaked a-wave is closely related to the appearance of the two first oscillatory potential. Secondly, the division of the a-wave in the immature animal may be caused by the intrusion of the first oscillatory potential. Thirdly, the presence of a split a-wave before spontaneous opening of the lid seems to indicate a state of comparatively progressed maturity of neuronal adaptation. PMID- 8475711 TI - The proliferative response during regeneration of a ringshaped defect in the corneal epithelium. AB - The aim of the present study was to investigate the regenerative ability of the central corneal epithelium in an in vivo situation, as previous studies have been contradictory regarding the proliferative potential of these cells. Paracentral ringshaped defects were made in rat corneal epithelium, using filter paper soaked in n-heptanol. Cell counts, labelling indices and mitotic rates were measured in sections from the corneal and the adjacent conjunctival epithelium 12 and 28 h after the injury. The cell counts indicated that also central corneal epithelial cells migrate in the early phase of wound healing. No proliferative response was seen in the central corneal epithelium after 12 h. At 28 h both the peripheral and central corneal cells showed an enhanced labelling index, while the mitotic rate only was increased in the periphery. Different cell cycle times and different levels of differentiation of the cell population across the cornea may explain the delayed proliferative response in the central cornea. PMID- 8475712 TI - Cell kinetics of normal and healing rat corneal epithelium during organ culture. AB - Local epithelial proliferation in corneal, limbal, and conjunctival rat epithelium was investigated during organ culture of corneo-scleral shells, by relating the number of tritium labelled cells to the total number of cells (labelling index). The changes in labelling index after a mechanically induced central corneal abrasion were also studied. Local labelling indices were measured 2 h, 1, 2, 4 and 7 days after incubation. The average labelling index increased in un-abraded specimens 4-fold after 4 days of incubation, while the total number of cells only decreased 30-50%. In eyes with a central corneal abrasion the labelling index increased 10-fold in the surrounding epithelial cells after 1 day. The labelling index of the limbal and conjunctival epithelial cells increased to the same extent after 2 days of incubation. The finding of a reduced total number of cells and an increased cell proliferation in un-abraded eyes may be explained by increased loss of mature cells normally producing growth inhibitory substances (chalones). Alternatively, the culture medium may contain an excess of growth-stimulatory substances. The results also suggest that the proliferative response spreads in a centrifugal direction during in vitro healing of a central corneal abrasion. PMID- 8475713 TI - The effect of age on human corneal thickness. Statistical implications of power analysis. AB - The corneal thickness of 108 human subjects, ranging from 17 to 75 years of age, was measured using ultrasound pachometry. One central, four mid-peripheral and four peripheral corneal positions along the vertical and horizontal meridians were assessed using ultrasound pachometry. No significant differences were found in the thicknesses of the central, midperipheral or peripheral cornea with increasing age using analysis of variance. These results suggest that ageing has no significant effect on human corneal thickness between the ages of 16 to 75 years. However the high Type II error probability (beta = 0.90) suggests that 108 subjects (18 in each age group) were insufficient to adequately answer the question. Thus power analysis may help explain the conflicting reports available in literature. The diversity in data interpretation may be due to the statistically small sample sizes used in most studies. Power analysis shows that at least 80 subjects are needed in each age group (480 subjects in total) before a statistically reliable test of the null hypothesis is possible. This study emphasizes the importance of power analysis in calculating an adequate sample size. PMID- 8475714 TI - The effect of age on the edema response of the central and mid-peripheral cornea. AB - Corneal edema was induced by a 2-h closed-eye wear of a thick hydrogel contact lens. Corneal edema production and edema recovery responses were measured in the central and mid-peripheral (3 mm inferior) cornea of 10 younger (20.4 +/- 2.0 years) and 10 older (69.0 +/- 3.4 years) subjects using optical pachometry. The amount of edema produced was not significantly different between the two corneal locations nor between the two age groups. The edema recovery rates of the central and mid-peripheral cornea were not significantly different in either the younger or older group. The edema recovery rates at both corneal positions were significantly faster in the younger group than in the older group. The results of this study suggest that the mechanisms that control edema production and recovery in the inferior mid-peripheral cornea are similar to those previously described in central and temporal mid-peripheral locations. Ageing appears to influence the edema production and recovery mechanisms of both the central and mid-peripheral cornea in similar ways. PMID- 8475715 TI - Break-up time and lissamine green epithelial damage in 'office eye syndrome'. Six month and one-year follow-up investigations. AB - Break-up time and lissamine green epithelial damage were re-investigated among 90 office workers after six months in 60 and after one year in 73. There was fairly good correlation with a rank correlation of about 0.40 between both break-up time and lissamine green staining epithelial damage at the initial investigation and at the two re-investigations. All correlations were found highly statistically significant. The results indicate that the manifestation of dry eyes in office workers to a great extent is chronic and without seasonal variation, at least as long as the subject remains in the office environment. PMID- 8475716 TI - Further evaluation of a method used for investigation of toxic drug effects. Effect of gentamicin on rabbit corneal endothelium. AB - Further evaluation of a method suitable for investigation of toxic drug effect was performed. Rabbit corneas kept in organ culture were exposed to gentamicin for 24 h, and their weights were recorded. The weight increase observed in all specimens was significantly higher (p < 0.0001) in the corneas exposed to gentamicin 0.6 mg/ml (n = 7) than in the controls (n = 14). This was not the case for the corneas exposed to 0.3 mg/ml and 0.1 mg/ml. The accuracy of each weight recording was tested by repeated recordings. The standard deviation (SD) was less than 1%, and there was no significant difference between series performed by two different recorders. The reproducibility of the test was focused upon by calculating the SD of the control group, and by comparing the present results with the results of a control group in a recently published study (Medin 1992). The SD was approximately 2.8%, and no significant difference was found. PMID- 8475717 TI - Assessment of tear drainage by fluorescein dye disappearance test after experimental canalicular obstruction. AB - Controversy exists about the role of upper and lower canaliculi in tear drainage. Fluorescein dye disappearance test was used to evaluate tear drainage after experimental obstruction of upper, lower, neither or both canaliculi in 18 subjects by hydroxypropil cellulose rods. When both canaliculi were occluded marked impairment was noted in all subjects (p < 0.05). Monocanalicular obstruction (either upper or lower) generally resulted in minimal impairment in most of the cases. Only 11% of upper canalicular obstruction and 20% of lower canalicular obstruction resulted in marked impairment. There was no significant difference between upper and lower canalicular obstruction (p < 0.05). In this study it is concluded that both upper and lower canaliculus have equal importance in tear drainage. PMID- 8475718 TI - Evaluation of gray scale steps on Scheimpflug photographs. AB - A method for the calibration of gray scale density in a Scheimpflug photograph was established. Based on the result of statistical analysis, it was found that variability in the film emulsion was insignificant if the measuring area > or = 0.01 mm2. Each lens image should be calibrated with the reference gray scale in the same photograph. Photometric readings of the lens image was converted to gray scale levels. This conversion can be obtained from fitting photometric readings of the gray scale as a function of gray scale steps with a third order polynomial. Adopting this calibration procedure, 95% of estimated nuclear densities are within +/- 3-5% of the real value. PMID- 8475719 TI - On the Stiles-Crawford effect and ocular imagery. AB - To study the modifying effect on spherical aberration of the retinal directional sensitivity (the Stiles-Crawford effect), ocular imagery was simulated by computer ray-tracing in a phakic and a pseudophakic model eye. The Stiles Crawford effect was found to reduce the distance between the paraxial focus and the effective least blur focus. The modifying effect on spherical aberration was found to be insignificant for pupil sizes below 4 mm, and to increase in magnitude above this size. For an 8 mm pupil, the effective focus was found to move 0.3 mm and 0.2 mm toward the paraxial focus for the phakic and the pseudophakic eye, respectively. This corresponded to a shift of 1.0 D and 0.6 D in the spectacle plane, respectively. The modifying effect of the retinal directional sensitivity should be taken into account in the theory of ocular refraction and in objective keratometry and refractometry. PMID- 8475720 TI - The effect of topical steroid on postoperative corneal edema and endothelial cell loss after intracapsular cataract extraction. AB - In a prospective study of 89 patients the postoperative corneal edema and endothelial cell count was studied after cataract extraction. A double blind investigation was performed as the patients during the first 6 postoperative days were treated with three different types of eye-drops: Maxidex, Pred-Forte 1% or placebo, all containing Benzalkonium Chloride 0.004%. The content of steroid in Maxidex and Pred-Forte was equivalent. We found no significant difference in estimates of endothelial cells in the three groups postoperatively. Corneal edema was less in the two groups treated with steroid. There was no significant difference between the two postoperative groups (p > 0.05) treated with Maxidex and Pred-Forte. The group treated with Pred-Forte showed significantly less postoperative corneal edema, calculated as the graphical area represented by the increase of central corneal thickness (CCT) after operation. PMID- 8475721 TI - The ultrastructure of Elschnig's pearls in a pseudophakic eye. AB - The giant cells forming the Elschnig pearl mass after extracapsular cataract extraction are derived from lens epithelium. They are interconnected by gap junction and desmosome-like structures. They stain homogenously and show few organelles. Active autolysis was demonstrated in some regions. The ultrastructural features of the giant cells in this type of secondary cataract share many of the characteristics of fiber cells. Because of profound changes in the environment postoperatively, these cells have developed other shapes and characteristics than normal lens fiber cells. PMID- 8475722 TI - IOL power mislabelling. AB - Prompted by four cases of IOL power mislabelling, a method was developed which allowed the measurement of the IOL power using a keratometer. The principle of operation was to measure the curvature of the steepest surface of the IOL through a minus lens by which the size of the mires was brought into the measuring range of the keratometer. With this method the IOL power was checked in three random IOL samples from three companies. Although no large errors in IOL power labelling were encountered in these samples, the error of labelling was found to differ significantly between the companies. It was concluded, that poor manufacturing control of IOL power may add to the sources of error in IOL power prediction. PMID- 8475723 TI - Human vertical eye movement responses to earth horizontal pitch. AB - The vertical eye movements in humans produced in response to head-over-heels constant velocity pitch rotation about a horizontal axis resemble those from other species. At 60 degrees/s these are persistent and tend to have non reversing slow components that are compensatory to the direction of rotation. In most, but not all subjects, the slow component velocity was well characterized by a rapid build-up followed by an exponential decay to a non-zero baseline. Super imposed was a cyclic or modulation component whose frequency corresponded to the time for one revolution and whose maximum amplitude occurred during a specific head orientation. All response components (exponential decay, baseline and modulation) were larger during pitch backward compared to pitch forward runs. Decay time constants were shorter during the backward runs, thus, unlike left to right yaw axis rotation, pitch responses display significant asymmetries between paired forward and backward runs. PMID- 8475724 TI - Postural control and age. AB - We quantified the effect of vision, pressoreceptor function and proprioception on the postural stability at different ages. Altogether 212 healthy volunteers (ages from 6 to 90 years) were examined by using a computerised force platform. The sway velocity (SV) was measured with eyes open and eyes closed during quiet stance on a bare platform and a foam plastic covered surface. In addition, to study the proprioceptive system, pseudorandom vibration perturbation was applied on the calf muscles. The SV showed a U-shaped curve: the children and the oldest swayed most. Equilibrium was most stable around 50 years. The visual system was of most importance for balance control in the old. The children were sensitive of pressoreceptor and proprioceptive perturbation, indicating the importance of these systems for their postural control. PMID- 8475725 TI - Voluntary eye movement tests in patients with insulin-dependent diabetes mellitus. AB - Eye movement tests (saccade tests: reaction time, peak velocities and accuracy, and the eye tracking test) were studied in 53 insulin-dependent diabetic (IDDM) patients and 42 randomly selected non-diabetic control subjects, aged between 20 and 40 years. All subjects had central visual acuity of at least 0.1 in one eye, and none had ophthalmoplegia. The reaction time was longer and the accuracy decreased in the saccade test in diabetic patients as compared to control subjects. Peak velocities tended to be slower in diabetic patients, but no significant differences between diabetic and non-diabetic subjects were observed. The maximum eye movement velocities were reduced at all target velocities in diabetic patients as compared to control subjects. These findings can be explained on the basis of many potential disturbances in the central nervous system. Only the duration of diabetes had a clear association with maximum smooth pursuit eye movement velocities in the eye tracking test. Microvascular complications (retinopathy, nephropathy), autonomic neuropathy or metabolic control (high fasting blood glucose and glycated hemoglobin A1c) had no clear association with the results of eye movement tests. In conclusion, insulin dependent diabetes mellitus deteriorates the visuomotor responses. PMID- 8475726 TI - The otolithic organ in the developing chick embryo. Scanning electron microscopic study on the utricular macula. AB - The long and short axes of utricular maculae were measured to calculate growth curves using an ocular micrometer under stereomicroscope. The mean lengths of the long and short axes on the 6th incubation day were 0.06 mm and 0.05 mm, respectively. Thereafter: 1.00 mm and 0.74 mm on the 11th incubation day; 1.34 mm and 1.03 mm on the 15th incubation day; and on hatching 1.51 mm and 1.07 mm, respectively. The surface structure, particularly the otoconia and the sensory hairs of the utricular maculae, on the 4.5th incubation day to the 7th post hatching day of White Leghorn chicks were observed with a scanning electron microscope (SEM). A number of microvilli and primary cilium on the inner surface of the otocyst were found between the 4.5th and the 5th incubation day. Immature sensory hairs appeared on the 5th incubation day. The polarity of the sensory hairs became evident on and after the 9th incubation day. Mature sensory hairs were seen all over the utricular maculae between the 1st and the 3rd post hatching day. Mature sensory hairs were mainly seen near the striola, and immature ones peripherally. Then, the various forms in the maturation phase of sensory hairs were seen between the striola and the periphery. These arrangements suggest some process of maturity from the peripheral region to the central striola region. Immature otoconia were first seen on the 6th incubation day. Mature otoconia were recognized on and after the 11th incubation day, and they were observed on the whole surface of the utricular maculae. Global substances on the macula with a rough surface and spongy structure were observed suggesting otoconial precursors transforming themselves into otoconial crystals. PMID- 8475727 TI - Effects of electrical stimulation of the superior cervical ganglion on cochlear blood flow in guinea pig. AB - It has been proposed that cochlear blood flow (CBF) is controlled in part by the sympathetic nervous system. In the present study the effect of electrical stimulation of the superior cervical ganglion (SCG) on CBF in guinea pigs was investigated using laser Doppler flowmetry (LDF). Animals were anesthetized with diazepam and fentanyl and the SCG was exposed. A custom-designed bipolar cuff electrode was fixed around the ganglion and 1 ms biphasic current pulses were injected at 0.15 mA to 1.5 mA, 6 Hz. Bilateral CBF was monitored, while the ganglion was stimulated for 3 or 5 min before and after the ascending sympathetic trunk and nerve branches from SCG were sectioned. Electrical stimulation of 0.5 mA caused the ipsilateral CBF (CBFi) to decrease 11.7% +/- 1.3 from the baseline (BL), while the contralateral CBF (CBFc) increased slightly due to the change in systemic blood pressure (BP). A linear relation was observed between the level of current stimulation and evoked reduction in CBF. Cervical sympathetic trunk section (between the SCG and the middle cervical ganglion) did not influence the pattern or the amplitude of CBF change in response to electrical stimulation of SCG. Sectioning the efferent fibers of the medial inferior and medial superior branch of the SCG only minimally reduced the amplitude of the CBF decrease evoked by electrical stimulation. However, sectioning the superior lateral branch abolished this decrease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475728 TI - Cytotoxic effects on hair cells of guinea pig cochlea produced by pneumolysin, the thiol activated toxin of Streptococcus pneumoniae. AB - The cytolytic toxin, pneumolysin, from the gram positive bacterium, Streptococcus pneumoniae, when perfused through the scala tympani of the guinea pig cochlea reduced the amplitude of both the compound action potential and the cochlear microphonic potential. When the surface of the organ of Corti was examined by scanning electron microscopy, both inner and outer hair cells and supporting cells were found to be damaged. Inner hair cells and outer hair cells of row 3 were the most susceptible to damage by pneumolysin, followed by row 2 and then by row 1 of the outer hair cells. Damage to hair cells included disruption and splaying of stereocilia, loss of stereocilia and complete dissolution of hair bundles. Apical surfaces of hair cells and supporting cells were torn, pitted and cratered with shrinkage and tearing of cell boundaries. Within the dose range perfused (0.05-1 micrograms/microliters in a 10 microliters aliquot), the magnitude of the physiological and anatomical lesions was concentration dependent. The cytotoxic effects of pneumolysin reported here may be clinically significant factors in deafness caused by meningitis and otitis media in humans. PMID- 8475729 TI - The MRL-lpr/lpr mouse: a potential model of autoimmune inner ear disease. AB - Most attempts at developing a model of autoimmune inner ear disease have focused on the immunization of healthy animals with cochlear tissue. We have chosen an alternate route of studying this entity utilizing the MRL-lpr/lpr (Lupus) mouse, an animal known to spontaneously develop multisystemic, organ nonspecific autoimmune disease. We report on the auditory pathology found in animals at early stages of this systemic disease. At the onset of clinical signs of illness (cachexia, weight loss, lethargy) animals were sacrificed and their cochleas and kidney prepared for morphologic analysis. Significant pathology was seen in the MRL/lpr animals involving the basal and middle turns of the cochlea which could not be correlated with the presence or degree of glomerulonephritis. Findings included outer and inner haircell degeneration, strial edema and degeneration, and an acellular infiltrate in the tunnel of Corti. Cochlear pathology was not found in control animals. Thus, at early stages of systemic disease, MRL/lpr mice manifest significant cochlear pathology not seen in control animals. The implications of these results with regard to the pathogenesis of these lesions as well as their clinical relevance are discussed. PMID- 8475730 TI - Evidence of direct communication of bone marrow cells with the endolymphatic sac in experimental autoimmune labyrinthitis. AB - In experimental autoimmune labyrinthitis, we found that the guinea pigs sensitized with bovine inner ear antigen (IEAg) developed cellular infiltration within the endolymphatic sac (E. sac). In this study, we investigated the distribution of immune mediated cells within bony vascular channels. The channels, which are normally found around the E. sac, are tiny and contain few immune-mediated cells. In contrast, in guinea pigs sensitized with IEAg bony vascular channels were large and contained immune-mediated cells. We hypothesize that immune-mediated cells in these channels are the result of the immune response directed against inner ear antigen, and that some immune-mediated cells seen in the E. sac during inner ear inflammatory events have migrated from the adjacent bone marrow. PMID- 8475731 TI - Torsion of the human semicircular canals and its influence on their angular relationships. AB - We used a computer-aided three-dimensional reconstruction and measurement method to measure torsion of the the semicircular canals (SCCs) in 10 normal human temporal bones from 10 individuals (3 months to 76 years old). Torsion of each SCC was measured as the angle between the "standard line" (the line connecting the ampullated and nonampullated ends of the SCC) and the plane of greatest SCC torsion. Torsion was greatest for the anterior SCC (16.4 +/- 3.6 degrees), followed by the lateral SCC (9.5 +/- 6.7 degrees) and the posterior SCC (8.5 +/- 4.2 degrees). The angles between the overall plane described by each SCC and the other SCCs between the anterior and lateral, the anterior and posterior, and the posterior and lateral SCCs were also measured and were found to be 78.7 +/- 10.0, 107.9 +/- 5.5, and 87.3 +/- 6.9 degrees, respectively. Finally the angles between the torsion plane of each SCC and the others were measured and found to be 92.6 +/- 15.4, 95.8 +/- 11.2, and 90.9 +/- 8.3 degrees, respectively. These results indicate that on average torsion in the SCCs tend to bring the angle between pairs of SCCs close to a right angle. This tendency to have a right angle between SCCs is thought to promote optimal vestibular function. Speculation is offered regarding the etiology of the greater torsion of the anterior SCC. PMID- 8475732 TI - X-ray microanalytical determination of P, S and K concentrations in the gelatinous membrane of the utricle. AB - Electron probe X-ray microanalysis was used to determine the concentrations of P, S and K (Cp, CS, CK) in the gelatinous membrane of the mouse utricle. The otolithic membranes were plunge-frozen in liquid N2, freeze-dried and carbon coated. Quantitative analysis was carried out with an energy dispersive detector using the peak-to-background ratio method and different concentrations of KH2PO4 and K2SO4 salts dissolved in dextran solutions to calibrate the microprobe. P, S and K were measured and their concentrations plotted as bar graphs to study the frequency distributions. Regression analysis revealed a dependence between the concentrations of P and K (CK = 1454.10 - 2.83 CP, r = -0.68745, p < 0.05), and P and S (CS = 43.18 + 0.23 CP, r = 0.66949, p < 0.05); however, no correlation was found between CK and CP (r = -0.25424). The findings obtained in the present study show an inverse relationship between P and K ions, and direct relationship between P and S in the gelatinous membrane of the utricle. PMID- 8475733 TI - Bone tissue kinetics in the surgically disarticulated dog incus. AB - The incus of the right ear from 4 growing mongrel dogs was surgically disarticulated and left in the middle ear space. The external auditory canal was then filled with teflon paste and sutured. After 6 weeks (D-6 group) and 13 weeks (D-13 group) the animals were sacrificed. The right experimental incus and the left control one were embedded in methyl methacrylate and sectioned in single 50 microns-thick sections according to the principal axis of the two processes. On the microradiographs of each section we evaluated the thickness of the body and of both processes and the percentage area of the primary channels of the secondary osteons and that of the appositional bone tissue. The thickness of the body and of the two processes was more pronounced in all the experimental incuses, in which 6% (in D-6) and 8% (in D-13) of the total area were occupied by new appositional woven bone. In the body of the D-13 group, 9% of the pre existing bone was substituted by secondary osteons. The results indicate that the incus react to the variations of mechanical stimuli. PMID- 8475734 TI - Eustachian tube compliance in sniff-induced otitis media with effusion. A preliminary study. AB - Compliance and ventilatory functions of the eustachian tube (ET) were examined in 20 ears with sniff-induced otitis media with effusion (OME) and 16 ears with traumatic perforation of the eardrum (control) by the forced response test (FRT) including the compliance test, and by the inflation-deflation test. The tubal compliance showed no significant difference between two groups in the FRT. The inflation test revealed that the forced opening pressure was significantly lower in the sniff-induced OME group than in the controls. In the FRT, the active ventilatory dysfunction was also revealed to be significantly more common in the sniff-induced OME. These results suggested that most of the ETs with sniff induced OME seemed to have excessive patency and poor active opening ability, but may not be hypercompliant or "floppy". PMID- 8475735 TI - Secretory IgA-, IgG- and C3b-coated bacteria in the nasopharynx of otitis-prone and non-otitis-prone children. AB - The proportions of secretory IgA (SIgA)-, IgG- and C3b-coated bacteria obtained from a well-defined area on the posterior wall of the nasopharynx (NPH) close to the Eustachian tube were determined. Samples taken from 25 otitis-prone (OP) and 25 non-otitis-prone (NOP) children with normal serum levels of IgA and IgG were evaluated using an immunofluorescence assay. Both groups harboured significantly more nasopharyngeal bacteria coated with IgG than with SIgA (p < 0.001). The OP children had significantly fewer SIgA-coated bacteria (p < 0.05) but more C3b coated bacteria (p < 0.01) in the NPH than the NOP children had. No significant difference was noted between the two groups regarding IgG coating. The occurrence of Branhamella catarrhalis in the NHP was more pronounced in the OP group (p < 0.05). No significant differences in the occurrence of other middle ear pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus) or quantitative dominance of pathogens were noted between the two groups. Deficiency in SIgA coating of the nasopharyngeal bacteria may contribute to the otitis-prone condition. PMID- 8475736 TI - The relationship between nasal airway resistance and middle ear pressure in subjects with acute upper respiratory tract infection. AB - Middle ear pressure and nasal airway resistance were measured over 7 1/2h in 8 subjects (age 18-32) with symptomatic acute upper respiratory tract infection. The mean middle ear pressure was -13 +/- 1.5 daPa (s.e.m.) with a range between 65 to -140 daPa. The mean total nasal resistance was 0.4 +/- 0.02 Pa/cm3/s (s.e.m.) with a range between 0.20 to 1.28 Pa/cm3/s. Unilateral nasal airway resistance exhibited reciprocal fluctuations with a range between 0.18-3.60 Pa/cm3/s. The mean difference between the highest and lowest unilateral nasal resistance values for each subject was 1.48 +/- 0.22 Pa/cm3/s (n = 16). No correlation was found between unilateral nasal airway resistance and middle ear pressure. Total nasal airway resistance had an inverse correlation with middle ear pressure r = 0.32, r2 = 0.11, n = 176 (p < 0.001). The results indicate that the generation of a negative middle ear pressure in acute upper respiratory tract infection occurred in a manner consistent with intermittent obstruction of the Eustachian tube and gradual middle ear gas absorption. Rapid increases in middle ear pressure and the generation of a positive middle ear pressure were associated with nose blowing. No evidence was found to support the hypothesis that negative middle ear pressures are associated with sniffing. PMID- 8475737 TI - Acute frontal sinusitis: etiological factors and treatment outcome. AB - A retrospective analysis of patients with acute frontal sinusitis treated at Kuopio University Hospital between 1981 and 1990 was performed to define etiological factors, clinical course and response to treatment. The study comprised 91 patients, 67 men and 24 women, aged from 9 to 65 years with a mean age for men of 32 years and for women of 29 years. Thirty-nine patients (43%) had previously been suffering from seasonal or chronic rhinitis, which in 22 was allergic, in 15 vasomotoric and in 2 due to intolerance to acetylsalicylic acid. In one case there was a recent and in another an old nasal trauma. Forty-seven patients (52%) were hospitalized, the others treated as outpatients. All received medical treatment. In 49 patients (54%) there was contemporary maxillary sinusitis which was treated with irrigations. Nasal polyps were detected and removed in 18 patients (20%). Anterior ethmoidectomy was made in 11 patients (12%) and trephination of the diseased frontal sinus to avoid complications in 8 patients (9%). No complications occurred. In 5 patients (5%) acute frontal sinusitis recurred once and a chronic course was seen in another 5 patients of whom 3 had chronic allergic and one vasomotor rhinitis. PMID- 8475738 TI - Localization of site of obstruction in snorers and patients with obstructive sleep apnea syndrome: a comparison of fiberoptic nasopharyngoscopy and pressure measurements. AB - The site of obstruction in the upper aerodigestive tract in 20 snorers and/or patients with obstructive sleep apnea syndrome was determined by two methods: fiberoptic nasopharyngoscopy with the Muller manoeuvre and continuous, nocturnal pressure measurements in the upper aerodigestive tract supplemented with recording of O2 saturation and oro-nasal air-flow. Identical results were obtained by both methods in only 5 (25%) of the patients, whilst in 11 (55%) obstruction was recorded in the pharynx by the pressure method which could not be demonstrated by the Muller manoeuvre. The latter method is not sufficiently accurate and should no longer be used in the pre-treatment assessment of this group of patients. Measurement of pharyngeal pressure, O2 saturation and air-flow are recommended in the diagnostic work-up. PMID- 8475739 TI - Irradiation of rabbit submandibular glands. Histology and morphometry after 15 Gy. AB - Irradiation of rabbit submandibular glands with a single absorbed dose of 15 Gy caused tissue damage which persisted 4 and 10 months later. The injuries were studied by histology, measurement of gland weights and histomorphometry. Reduction of gland weight due to hypoplasia and missed weight gain were seen and the proportions of the three major intralobular compartments of the glands were altered being dependent on the interval between radiation exposure and observation time. The size of the lobules was reduced and extralobular fibrosis in the hilar region increased. The seromucous acini were partly atrophied, with successively changed architecture and reduced size of the granules. The serous tubules showed pronounced reduction of the granules at 4 months and a remarkable adenomatous regeneration at 10 months post irradiation. The striated ducts were almost unaffected during the observation time. Arteriolar changes were slight to moderate, and there was scarcely any capillary damage. The numbers of intra- and extralobular plasma cells were increased. PMID- 8475740 TI - T3N0 glottic carcinoma: DNA S-phase as a predictor of the outcome after radiotherapy. AB - In consecutive series of 326 laryngeal cancer patients, of 29 (9%) with stage T3N0 glottic carcinomas, 23 achieved complete local remission after curative radiotherapy and form the basis of the present investigation. Flow cytometry determinations of DNA-ploidy status and the S-phase fraction, and a "histopathological malignancy grading system" were evaluated as possible patient- and/or tumor-related predictors of local recurrence. Twelve patients (52%) were continuously disease-free after radiotherapy, whereas 10 (43%) manifested local recurrence, and one distant metastasis. The radiotherapy delivered to patients who later suffered from a local recurrence did not differ from those being continuously disease-free. The frequency of local recurrence was significantly correlated to patients whose primary tumours manifested a low S-phase fraction (p < 0.05). A low S-phase fraction may indicate slowly proliferating tumour-cells, which become more radioresistant on exposure to a series of fractionated doses, as their reassortment into sensitive phases will be proportionately slower. PMID- 8475741 TI - Tissue culture of the organ of Corti. AB - In 1975, Sobkowicz et al. (1) described long-term organotypic cultures of the organ of Corti of the newborn mouse. This paper provides detailed methods for dissection and maintenance of the isolated organ of Corti with its corresponding segment of spiral ganglion in culture. Descriptions and illustrations of cellular characteristics of the developing organ are carefully documented. The work is based on 19 years of experience and over one thousand cultures. Review of the literature and the application of the technique to research on the inner ear are provided. PMID- 8475742 TI - Dynamics of transcapillary fluid transfer and plasma volume during lower body negative pressure. AB - Lower body negative pressure (LBNP) is a stimulus frequently used to study reflex circulatory responses in humans. Studies have provided data on LBNP-induced blood pooling; however, the possibility that LBNP also might be associated with an important loss of plasma fluid has attracted little attention. Therefore this problem was analysed in male volunteers exposed to prolonged (10 min) high (70-75 mmHg) LBNP. Data on LBNP-induced blood pooling that were more reliable than in previous literature were also provided. LBNP caused early pooling of more than 870 ml of blood. Rapid filtration of plasma into the exposed tissues occurred throughout LBNP. The cumulative oedema in the legs and buttocks averaged as much as 460 ml, and additional quite large volumes of plasma apparently accumulated in other parts of the lower body. Concomitantly, there was compensatory absorption of extravascular fluid in the upper body. The net decrease in plasma volume (PV) was still large and averaged 491 +/- 29(SE) ml. Two aspects of the demonstrated process of transcapillary fluid fluxes and PV decline may be emphasized. Firstly, in conjunction with the primary large redistribution of intravascular volume, it certainly implies that LBNP is a potent stimulus as also indicated by a progressive increase in heart rate (HR) and a progressive decline in systolic pressure throughout experimental intervention. In fact, LBNP-induced circulatory stress clearly has bearings on the extreme hypovolaemic situation provided by the pressure-bottle haemorrhage technique used in animals. Secondly, it not only offers an interesting example of the dynamics of PV but appears to have more general validity with regard to states characterized by gravitational shifts of blood (hydrostatic load), like upright exercise and quiet standing. PMID- 8475743 TI - Lung to blood passage of albumin and a nonapeptide after intratracheal instillation in the young developing pig. AB - The passage via the lower respiratory tract of the macromolecule, bovine serum albumin (BSA, mol. wt = 67000) and the nonapeptide, 1-deaminocysteine-8-D arginine vasopressin (dDAVP, mol. wt = 1067), was assessed for 240 h after intratracheal instillation in young, developing pigs. The plasma levels of immunoreactive BSA increased with time, reaching a maximum between 36-86 h after instillation, and the main portion of BSA in plasma appeared intact, as assessed by crossed immunoelectrophoresis. The dDAVP levels reached a maximum after 1-3 h. The time to reach maximal plasma levels increased with the age of the pig for BSA, while no such effect was observed for dDAVP. The total lung passage, as calculated by dividing the area under the plasma level-time curve obtained after intratracheal instillation with that obtained after intravenous administration (elimination curve), showed no significant differences with age for BSA (21.8 +/- 9.0% in the newborn, 15.1 +/- 8.0% in the 2-day-old and 16.1 +/- 4.2% in the 70 day-old pigs). For dDAVP, a significant decrease in the total passage was obtained with age, from 74.6 +/- 9.4% in the newborn pigs to 44.1 +/- 13.3%, in the 2-day-old pigs (P < 0.001), and to 23.6 +/- 7.1% (P < 0.01) in the 70-day-old pigs. The study showed that the marker molecules, BSA and dDAVP, passed over the porcine lung into the blood circulation in high amounts, apparently inversely related to their molecular size. The total lung passage of dDAVP, but not that of BSA, was affected by changes with age, indicating that these two markers might traverse the lung epithelium via different routes that are differently affected during postnatal development. PMID- 8475744 TI - Morning increase in whole blood viscosity: a consequence of a homeostatic nocturnal haemodynamic pattern. AB - In a series of studies, we have shown that in non-human primates there is a consistent overnight fall in cardiac output and central venous pressure, and a rise in total peripheral resistance. This haemodynamic pattern is associated with a higher haematocrit level in the morning suggesting that these changes in the circulation are homeostatic adjustments to a nighttime fall in plasma volume. The present study was designed to test the hypothesis that in the morning whole blood viscosity also is higher. Whole blood viscosity was measured at shear rates of 450, 225, 90, 45, and 22.5 s-1 in each of six monkeys, on four occasions, at 2 week intervals, at 17.00 and 09.00 h the next morning. The average haematocrit was 4.2% higher in the morning than in the previous evening (P < 0.01). Viscosity decreased monotonically at progressively higher shear rates but was always significantly higher in the morning than in the evening (P < 0.01 at all shear rates). When viscosity was adjusted by covarying for haematocrit level, the morning/evening differences became non-significant. However, the morning/evening differences in linear trend of shear stress as a function of shear rate persisted. These findings add further support to our hypothesis that the nocturnal haemodynamic pattern in non-human primates is related to a reduction in plasma volume, and they also suggest that the morning rise in haematocrit is a major contributing factor to the elevated viscosity. PMID- 8475745 TI - Much more potent baroreflex sympathetic control of vascular resistance in the resting human limb than previously believed. AB - The concept that, in man, the sympathetic control of the resting limb vascular resistance is truly limited and thus strikingly different from animal species, was challenged in the present study. Analyses were performed in healthy male volunteers of reflex forearm vascular resistance changes evoked by lower body negative pressure (LBNP) ranging from low (15 mmHg) to high and barely tolerated (85 mmHg) levels. Graded LBNP was associated with graded increases in resistance. At high 85 mmHg LBNP the responses were pronounced with a rise in forearm resistance to no less than 120 mmHg ml-1 min 100 + ml soft tissue, on average, corresponding to a 377% increase above control. This drastic response seemed entirely neurogenic in origin and calculations, based on the likely assumption that a similar response occurred in all skeletal muscle and skin/(subcutaneous fat), showed that it permitted a marked increment in total systemic vascular resistance because of the fact that these tissues constitute so large a proportion of the body mass. The conclusion was reached that the studied tissues may serve as main targets for powerful homeostatic reflexes. It is also suggested, in contrast to current views, that the high-pressure arterial rather than the low-pressure cardio-pulmonary baroreceptors may be the main mediators of haemodynamically important vasoconstrictor responses. PMID- 8475746 TI - A search for arteriovenous anastomoses in human skin using ultrasound Doppler. AB - The possible existence of arteriovenous anastomoses (AVAs) in skin regions of the head and thorax has been investigated using the synchronous vasomotion of the AVAs. Simultaneous pairs of blood velocity recordings were made using pulsed, bidirectional Doppler ultrasound. In each pair of registrations, blood velocity was recorded in a reference artery supplying a skin area known to contain AVAs (the radial artery) together with one of four other arteries investigated, i.e. the facial artery, the angular artery, the temporal artery, and the cutaneous branches of the lateral thoracic artery. The typical large, regular fluctuations in blood velocities caused by synchronous vasomotion in the AVAs in the skin of the hand and fingers were observed invariably in the radial artery. Similar flow variations were found in the angular artery. The fluctuations in this and the radial artery were, in turn, found to be synchronous. However, we have not been able to find the flow pattern characteristic of AVA vasomotion in the temporal artery or in the cutaneous branches of the lateral thoracic artery. These results show that the skin area of the nose supplied by the angular artery contains AVAs. These AVAs partly may explain the important role of face skin in temperature regulation. These results also support the earlier assumptions that there are no or very few AVAs in the skin areas supplied by the temporal artery and the cutaneous branches of the lateral thoracic artery. PMID- 8475747 TI - Plasma potassium concentration and doppler blood flow during and following submaximal handgrip contractions. AB - The aim of the present study was to investigate the time-course of blood velocity in the forearm during and following isometric handgrip contractions and to reveal a possible temporal relationship between the circulatory response and venous effluent potassium concentration ([K]) not only during contractions but also during the post-exercise recovery period. Contractions of 15% maximal voluntary contraction (MVC) and 30% MVC with and without 3 min of arterial occlusion following the contractions were studied. All contractions induced a significant increase in venous plasma [K] from an average resting level of 4.0 to 5.0 mM during 15% MVC and 5.8 mM during 30% MVC. Blood velocity increased from a resting level of 0.07 to 0.22 m s-1 and 0.36 m s-1 during 15% and 30% MVC, respectively. MVC of 30% always elicited a larger blood velocity and [K] response than 15% MVC. Following the contractions hyperaemia was elicited. Recovery of the local blood velocity was markedly slower than the K recovery, since [K] remained significantly above resting level for only 25 s following 15% MVC and 45 s following 30% MVC, while blood velocity remained elevated for 2 min and more than 7 min following 15 and 30% MVC, respectively. Further, a larger hyperaemia following the occlusion was elicited as compared to the contraction without occlusion, in spite of [K] being lower immediately after the occlusion period than immediately after the contraction. Finally, [K] decreased below resting level in the recovery period while the blood velocity remained elevated. Therefore, the present study showed that the venous plasma [K] is not causally related to the prolonged post-exercise hyperaemia. The skin temperature remained unchanged during the contractions, while during the recovery period the skin temperature increased for several minutes. The major part of the temperature increase was likely to be due to conductance of heart from muscles to skin surface as a consequence of muscle hyperaemia. PMID- 8475748 TI - Association of breathing movements to the variability of heart rate and blood pressure in foetal lambs. AB - Heart rate (HR) variability and arterial blood pressure (BP) variability were analysed as functions of foetal breathing movements (FBMs) by means of power spectral analysis in seven foetal lambs during the third trimester of gestation. No evidence of FBM-related changes, either in mean HR, mean systolic or diastolic arterial pressures, were found. Mean arterial pulse pressure, HR variability, and BP variability increased during FBMs. The increase in BP variability occurred at frequencies higher than 0.35 Hz, i.e. those of FBMs. The increase in HR variability occurred at 0.07-1.0 Hz, i.e. at every frequency band except the lowest one. Thus, the increase in HR variability was not frequency-specifically related to FBMs. During FBMs the periodic variability of HR at frequencies > 0.35 Hz was only 10% of total HR variability. We suggest that the FBM-related changes of BP variability may be mediated by direct peripheral, hydraulic mechanisms. HR changes involve autonomic control systems: the vagal component of baroreflex seems to be relatively insensitive, whereas the very slow vasomotor component of HR variability is dominant. PMID- 8475749 TI - Functional and biochemical effects of a K(+)-ionophore on the isolated perfused rat heart. AB - Valinomycin, a K(+)-specific ionophore, influenced function and metabolism of isolated perfused rat hearts in a dose-dependent fashion. At a concentration of 0.05 micrograms ml-1 in perfusion fluid a 50% reduction of heart rate (HR) and a 90% reduction in max dP/dt were observed. These effects were paralleled by a substantial decrease of myocardial energy charge from about 0.80 to 0.20. A 2.5 fold increase in tissue lactate concentration indicated an increased rate of glycolytic activity. Low ATP combined with high ADP and AMP levels as found in these valinomycin-treated hearts is known to promote phosphofructokinase activity and may explain the elevated lactate levels. A significant increase in the concentrations of adenosine, IMP and inosine was observed as well. PMID- 8475750 TI - An age-related type IIB to IIX myosin heavy chain switching in rat skeletal muscle. AB - A novel fast-twitch motor unit type, called the IIX-myosin heavy chain (MHC) motor unit, identified by the glycogen depletion technique together with a series of monoclonal antibodies (mAbs) specific for MHCs, has been isolated recently in the rat tibialis anterior muscle. In young animals, this unit has physiological, biochemical and morphometrical properties which separate it from the IIA- and IIB MHC motor units. In old age, on the other hand, the IIX-MHC units display physiological, biochemical and morphometrical properties resembling the IIB-MHC motor units. Based on these results it was proposed that a transition from IIB to IIX motor units occurs during ageing. In an attempt to clarify this point, the MHC composition was identified by 6% SDS-PAGE and immunoblotting analysis, using specific mAbs antibodies, in the same fast-twitch tibialis anterior muscles in young (3-6 months, n = 9) and old (20-24 months, n = 16) rats from which the single motor units had been identified previously. The IIX-MHC comigrates together with the IIA-MHC band in 6% SDS-PAGE and only two MHC bands are observed in the rat tibialis anterior muscle, i.e. the IIA-IIX- and IIB-MHC bands. A significant increase (P < 0.001) in the average relative amount of the IIA-IIX MHC was observed in the old (45 +/- 17%) as compared to the young (23 +/- 4%) animals, accompanied by a corresponding decrease in IIB-MHC content. It was demonstrated in immunoblotting analysis that only trace amounts of IIA-MHC were detectable in the IIA-IIX-MHC band in both young and old TA muscles, indicating a substantial increase in the IIX-MHC content in old age. Thus, the present results together with previous observations at the motor unit level strongly support an age-related motor unit transition from type IIB- to IIX-MHC. PMID- 8475751 TI - Gross efficiency of muscular work during step exercise at -15 degrees C and 21 degrees C. AB - In an effort to assess the effect of ambient temperature on the gross efficiency (Effg) of step exercise 12 subjects performed a modified step test either at -15 degrees C or 21 degrees C ascending to three different heights (corresponding to light, moderate and heavy work), for 20 min each with a frequency of 18 steps min 1. Heart rate (HR), rectal temperature, skin temperatures and heat flux from skin were continuously measured. Oxygen consumption was measured during the last 5 min of each step height and perceptions of thermal sensation were recorded. The results indicate that, while using conventional clothing adequate in these temperatures, Effg is altered in a contradictory manner. At -15 degrees C Effg increased with increasing work load, whereas at 21 degrees C it decreased when the work load increased. The highest Effg (heavy work at -15 degrees C and light work at 21 degrees C) values are reflected as rather similar rectal temperatures. (37.4-37.7 degrees C) and identical mean skin temperatures (32.8 degrees C) as well as the same (slightly warm) thermal sensation of the legs. At -15 degrees C the lowest Effg in light work was probably due to the need to warm up the muscles. At 21 degrees C, on the contrary, the activation of heat dissipation systems was probably responsible for the lowest Effg in heavy work. PMID- 8475752 TI - Relationship between blood buffering properties, erythrocyte pH and water content, in gray seals (Halichoerus grypus). AB - The separated plasma of gray seals (Halichoerus grypus) has an unusually high non bicarbonate buffering capacity (beta NB = d[HCO3-]/dpH = -21 Slykes; Slyke = mmol l-1 pH unit-1). To examine whether this represents a trait of mammalian carnivora, or is related instead to deep diving, we examined blood from dog and killer whale, respectively. The beta NB of separated plasma of dog was typically low (-4 to -8 Slykes), as in other mammals, whereas that of the whale (-13.5 Slykes), while significantly higher than dog, was not nearly as high as in seal. As one would theoretically predict of a blood system with exceptionally high extracellular buffering and functional anion exchange across the erythrocyte membrane, there was little difference in the buffer slope between true plasma and whole blood of seal. This appears to be a novel pattern of CO2 carriage in mammals. Erythrocyte ion concentrations were similar to other mammalian carnivora, with intracellular sodium concentration being high and potassium low. The red cell water content was unaffected by changes in oxygen saturation and tended to decrease when extracellular pH decreased below 7.4. Apart from the comparatively elevated Bohr factor, -0.518 as a function of extracellular pH and 0.550 as a function of red blood cell pH, the blood oxygen binding properties were similar to terrestrial mammals of similar size. PMID- 8475753 TI - Muscle vitamin E levels following acute submaximal exercise in female rats. PMID- 8475754 TI - Sequential changes in the splanchnic circulation during continuous endotoxin infusion in sedated sheep: evidence for a selective increase of hepatic artery blood flow and loss of the hepatic arterial buffer response. AB - On-line recording of the sequential changes in systemic, pulmonary, mesenteric, hepatic and renal circulations during onset of endotoxaemia and at 24 h of established hyperdynamic sepsis were evaluated in seven chronically instrumented and sedated sheep receiving a continuous intravenous infusion of Escherichia coli endotoxin (20 ng min-1 kg-1). A transient and significant (P < 0.05) pulmonary arterial vaso-constriction was noted after 13 +/- 4 min, and was followed immediately by a simultaneous significant decrease of coeliac trunk, superior mesenteric artery, and portal vein blood flow to below 50% of baseline values. The superior mesenteric artery and portal vein blood flows partially recovered pre-endotoxin levels to 69 and 75% of baseline, respectively, after 70 min of endotoxin infusion. In contrast, the coeliac trunk blood flow remained reduced for a more prolonged period of time, but then completely recovered baseline values at 100 min. The response of the hepatic artery was biphasic, and consisted of a transient (5-10 min) vasoconstriction at 40 min followed by transitory increase of hepatic artery blood flow reaching a maximum of 921% of baseline values at 102 min. Contrasting with the early changes observed in mesenteric vascular resistances mostly unrelated to systemic haemodynamics, the response of the renal vasculature appeared to be more dependent on changes of renal perfusion pressure. A follow-up at 24 h revealed that the continuous intravenous infusion of endotoxin reproduced some of the most characteristic features of human sepsis with increased cardiac output and decreased vascular resistances of all vascular beds. We conclude that hepatic artery blood flow is selectively and considerably increased in early endotoxaemia in sheep independently of changes in portal vein blood flow, suggesting a disregulation of the physiologic hepatic arterial buffer response, most probably secondary to an increased liver oxygen demand required for phagocytosis, transport, and digestion of the the sudden overload of bacterial endotoxins. PMID- 8475755 TI - Vascular characteristics influence the aortic ultrasound Doppler signal: computer and hydraulic model simulations. AB - There is an increasing demand for non-invasive methods for the assessment of left ventricular function. Ultrasound Doppler methods are promising, and the early systolic flow velocity signal immediately distal to the aortic valve has been used clinically for this purpose. However, the signal is influenced not only by left ventricular ejection but also by systemic vascular characteristics. Their relative contribution to the time-velocity signal has not been analysed in depth previously. A theoretical analysis, based on a three-element Windkessel model, neglecting peripheral outflow in early systole and assuming linear pressure rise, was therefore tested in computer and hydraulic model simulations where peripheral outflow was included. Significant changes in early aortic flow velocity parameters were found when vascular characteristics were altered. As predicted by the theory, with a standardized aortic valve area and aortic pressure change, the simulations confirmed that maximal flow velocity is related to compliance of the aorta and the large arteries, and that maximal acceleration is inversely related to the characteristic impedance of the aorta. Therefore, maximal velocity and acceleration can be used for assessment of left ventricular function only in situations where vascular characteristics can be considered relatively constant or where they can be estimated. PMID- 8475756 TI - Selective brain cooling in resting and exercising Norwegian reindeer (Rangifer tarandus tarandus). AB - The threshold body core temperature for selective brain cooling (SBC) as well as the slope of brain cooling were determined in three Norwegian reindeer (Rangifer tarandus tarandus) during rest and during exercise. Brain temperature was measured in the hypothalamus (Thypo) and blood temperature (Tblood) was measured either in the right carotid artery or in a few cases in the right atrium of the heart. During rest the animals were subjected to ramp-like increases of Tblood by means of a thermostatically controlled water circulated heat exchanger (HE) introduced into the rumen via a chronically implanted rumen cannula. During exercise the animals ran on a treadmill at a speed of between 5.5-8.0 km hr-1 and a slope of 13.5 degrees for periods of 30-60 min. The elevation of Tblood during both rest and exercise resulted in significant amounts of SBC. The mean threshold for SBC (Thypo = Tblood) during rest was 38.7 degrees C. The threshold for SBC was elevated significantly to 39.5 degrees C during exercise. The mean slope of SBC (increase of SBC per degree increase of Tblood) was 0.82 both during rest and exercise. PMID- 8475757 TI - Charge density of renal interstitium. AB - The charge density of renal interstitium was analysed from the volume of distribution of negative native albumin as compared with neutralized albumin, labelled with 125I and 131I, respectively. The experiments were conducted by infusing the two probes intravenously at a rate which kept the plasma concentrations stable. The concentration in renal hilar lymph, C(lymph)(t), will then obey the function C(lymph)(t) = C(lymph)(t infinity) (1-exp-Kt), where C(lymph)(t infinity) is the steady state concentration and K the time constant for passage of the tracer through the renal interstitium--the former is dependent on the permeability of the peritubular capillary membrane, whereas the time constant is inversely related to the interstitial distribution volume of the tracers. The lymph-to-plasma concentration ratio (L/P-ratio) of negative, native albumin was found to be lower than that of neutralized albumin, a finding suggesting that the peritubular capillary membrane is negatively charged. Regarding the interstitium, it was calculated from the respective time constants, K, that the interstitium/lymph concentration ratio of negative native albumin was 0.96 +/- 0.06 of that of neutralized albumin. This suggests the presence of negative fixed charges repelling negative native albumin. However, since the calculated charge density of -1.8 +/- 1.2 mEq l-1 was not significantly different from zero, it is concluded that the renal interstitium is uncharged. This does not, however, rule out the possibility that, for example, negative groups are fixed to the interstitial matrix, merely that the average fixed charge density of renal interstitial fluid is negligible. PMID- 8475758 TI - Endurance training increases skeletal muscle lactate transport. AB - Lactate accumulation in skeletal muscle is reduced after a period of endurance training. Explanations for this phenomena include the increased oxidative capacity of the muscle, a reduction in lactate production, and increased lactate clearance. Muscle membrane transport of lactate can be seen to be a fundamental aspect of such clearance, and transmembrane lactate flux may well be an important aspect of the training response in skeletal muscle. Therefore, the lactate transport capacity in skeletal muscle sarcolemmal membranes in endurance-trained and sedentary rats was investigated. Training consisted of 6 weeks of progressively increased treadmill exercise. Twenty-four hours before being killed, both the trained and sedentary animals completed a brief exercise bout. Studies of lactate transport (zero-trans) were conducted using highly purified sarcolemmal vesicles. When low concentrations of L-lactate (1 mM) were used a 59.4% increase in lactate transport was observed (P < 0.05). However, when a high concentration of lactate (50 mM) was used no change in lactate transport was found (P > 0.05). Several interpretations are possible for these observations: (1) that there is an alteration in the Km but not the Vmax of the lactate transport system in skeletal muscle membranes; and (2) that specific changes occur in selected isoforms of the lactate transport protein which may co-exist in muscle. PMID- 8475759 TI - Intravenous saline infusion in rat increases hyaluronan efflux in intestinal lymph by increasing lymph flow. AB - The output of hyaluronan in mesenteric lymph was studied in anaesthetized rats to allow estimation of the turnover rate. The duodenum/jejunum contained 45 micrograms of this glycosaminoglycan per g wet tissue weight. In fasted rats the concentration of hyaluronan in postnodal lymph averaged 15 micrograms ml-1 and the mean efflux was 2.1 micrograms h-1, corresponding to a daily removal of 10% of the intestinal hyaluronan content. An intravenously injected bolus of 0.9% saline 4 ml 100 g-1 followed by an infusion of the same amount per hour increased the hyaluronan concentration in lymph transiently to 22 micrograms ml-1. During the 8-h i.v. infusion the hyaluronan output remained five times above control due to the high lymph flow. Water and hyaluronan content of the small intestine remained unaltered despite the saline load, the maintained tissue level of hyaluronan suggests an increased rate of synthesis. PMID- 8475760 TI - Effect of allopurinol on myocardial purine release after total ischaemia in isolated rat heart. PMID- 8475761 TI - Blood plasma kinetics of arginine-vasopressin in camels. PMID- 8475762 TI - Neural representations for sensory-motor control, I: Head-centered 3-D target positions from opponent eye commands. AB - This article describes how corollary discharges from outflow eye movement commands can be transformed by two stages of opponent neural processing into a head-centered representation of 3-D target position. This representation implicitly defines a cyclopean coordinate system whose variables approximate the binocular vergence and spherical horizontal and vertical angles with respect to the observer's head. Various psychophysical data concerning binocular distance perception and reaching behavior are clarified by this representation. The representation provides a foundation for learning head-centered and body-centered invariant representations of both foveated and non-foveated 3-D target positions. It also enables a solution to be developed of the classical motor equivalence problem, whereby many different joint configurations of a redundant manipulator can all be used to realize a desired trajectory in 3-D space. PMID- 8475763 TI - On Fitts's and Hooke's laws: simple harmonic movement in upper-limb cyclical aiming. AB - Can discrete, single-shot movements and continuous, cyclical movements be reduced to a single concept? In the classical, computational approach to human motor behaviour, cyclical aimed movement has generally been considered to derive from discrete primitives through a concatenation mechanism. Much importance, accordingly, has been attached to discrete-movement paradigms and to techniques allowing the segmentation of continuous data. An alternative approach, suggested by the nonlinear dynamical systems theory, views discreteness as a limiting case of cyclicity. Although attempts have been made recently to account for discrete movements in dynamical terms, cyclical paradigms have been favoured. The concatenation interpretation of cyclical aimed movement is criticized on the ground that it implies a complete waste of mechanical energy once in every half cycle. Some kinematic data from a one-dimensional reciprocal (i.e., cyclical) aiming experiment are reported, suggesting that human subjects do save muscular efforts from one movement to the next in upper-limb cyclical aiming. The experiment demonstrated convergence on simple harmonic motion as aiming tolerance was increased, an outcome interpreted with reference to Hooke's law, in terms of the muscles' capability of storing potential, elastic energy across movement reversals. Not only is the concatenation concept problematic for understanding cyclical aimed movements, but the very reality of discrete movements is questionable too. It is pointed out that discrete motor acts of real life are composed of complete cycles, rather than half-cycles. PMID- 8475764 TI - Neuromotor noise and poor handwriting in children. AB - In this article Power Spectral Density Analysis of the velocity profile of handwriting tasks is applied to estimate movement noise in poor and proficient writers. It is hypothesized that poor writers are less effective in the inhibition of neuromotor noise. Evidence for this theory is found in an analysis of electronically sampled handwriting movements of 48 children from grade 2, 3 and 4 (mean ages 8, 9 and 10, resp.). Twenty-four were poor and 24 were good writers, as judged by their teachers. Subjects were matched on age, sex, handedness and educational level. They performed handwriting tasks consisting of simple garlands and arcades, or meaningless words built from the letters 'e', 'n' and 'm'. In the tasks stroke accuracy, size and rotational direction were systematically varied. The results reveal that movement times were not different between the two groups, but poor writers and good writers used different movement strategies. Movements of the less proficient children were larger and were produced with higher movement velocities. Power Spectral Density Analysis disclosed that handwriting movements of poor writers were substantially more noisy than those of proficient writers, with a consistent peaking of the noise energy in that region of the spectrum which is representative for neuromotor tremor. Also, poor writers were less successful in adapting the level of noise to increased accuracy demands of the tasks. The results support the view that deviant biomechanical strategies might be responsible for deficient motor performance. PMID- 8475765 TI - The role of proprioceptive information for the production of isometric forces and for handwriting tasks. AB - A patient showing a total loss of all the large sensory myelinated fibers but intact peripheral motor system produced simple isometric force pulses and more complex tasks like handwriting and drawing. Overall, the patient was able to perform the isometric force task with an accuracy that approached that of normal subjects. The writing tasks, however, proved to be more challenging. In absence of vision, the different forms and cursive trajectories forming letters (morphocinetic components) were preserved but their localization within the constraints of the graphic space (topocinetic components) were severely impaired. These results demonstrate that, in absence of visual information, proprioceptive information is necessary to calibrate the hand in space. PMID- 8475766 TI - Acquired agraphia caused by focal brain damage. AB - Motor and linguistic aspects of writing were evaluated in 31 subjects with focal damage in 1 of 3 regions of the left hemisphere: (1) dorsolateral frontal lobe sparing primary motor cortex (group FL), (2) parietal lobe (group PL), or (3) temporal lobe (group TL). A standard procedure was used to evaluate writing for grapheme formation, spatial arrangement, spelling, word selection, grammar, and perseveration. It was predicted that agraphia would be observed in all 3 groups, and that the most severe impairments would be associated with frontal lobe damage, particularly in aspects of writing dependent on sequencing (grapheme formation, spelling, and grammar). It was found that agraphia was common in all groups, particularly in the acute epoch, and that all groups showed considerable recovery of writing by the chronic epoch. Few differences were found between groups. However, the FL group was impaired on spelling and grammar relative to the PL group in the acute epoch and impaired on grammar relative to the TL group in the chronic epoch. The findings are consistent with the notion that writing relies on a distributed neuroanatomical network, which acts in concert to link fragments of visuomotor activity with component linguistic elements. PMID- 8475767 TI - Neurocomputing aspects in modelling cursive handwriting. AB - This paper describes a distributed modelling framework of the motor control processes that underly the planning of cursive handwriting. The model, that focuses on the hypothetical functions of the posterior parietal cortex combines a paradigm of self-organization (for building robust and coherent maps of the different motor spaces) with relaxation dynamics (for run-time incorporation of task constraints) and non-linear integration (for a smooth integration between via-points). PMID- 8475768 TI - A model for reaching control. AB - In this paper we propose that reaches are made to target postures which are selected by evaluating stored postures. Target postures are chosen by taking a weighted average of the stored postures, where the weights assigned to the stored postures depend on their effectiveness for the task. Movements from starting postures to target postures are achieved by reducing the distance, in joint space, between the two. The form of the movement depends on drive (assumed to decrease as less distance remains) and inertia. The model predicts the Power Law of learning, compensation for immobility of joints, changes in limb contributions depending on movement speed, asymmetric bell-shaped velocity profiles, velocity amplitude relations, Fitts' Law, and position-dependent variations in hand-path curvature. Planned extensions of the model may broaden its application-for example, to handwriting. PMID- 8475769 TI - Phonological and orthographic demands in the production of handwriting. AB - In an experimental handwriting task, with two parts, we varied the phonological and orthographic complexity of visually presented nonwords. Twelve adult subjects had to write these nonwords in shorthand as well as in Latin script. Phonological complexity was varied by presenting a nonword which included two identical vowel characters. These were either phonologically similar (simple condition) or phonologically different (complex condition). Orthographic complexity was varied by using nonwords which either have a graphemic format for shorthand that corresponds with the graphemic format that is applied for Latin script (simple condition) or a graphemic format for shorthand which is discrepant from the Latin script format (complex condition). It appeared that a higher degree of phonological and orthographic complexity led to a slower and less fluent performance in graphemes that preceded the actual locus of complexity of the nonword. Furthermore, complexity effects were by far the strongest under the production of shorthand. The results are interpreted from the point of view of a psychomotor theory of handwriting, which assumes that the spelling process of visually presented nonwords may follow a phonological or an orthographic (sublexical) route. The finding that orthographic complexity interferes with the production of a phonologically oriented task such as shorthand is interpreted as evidence in favour of an interactive transmission of information between these two processing routes. PMID- 8475770 TI - Does the production of letter strokes in handwriting benefit from vision? AB - In earlier studies the involvement of vision in handwriting was suggested by the finding that the production of a letter sequence in a condition without vision took more time and resulted in larger letter trajectories. The present study raises the question whether vision has an impact on the production of the individual up- and downstrokes constituting the letters. More specifically, the aim is to examine whether vision is employed either during the completion of a movement, or concurrent with the entire course of a stroke movement. Adult writers produced the letter sequence lelele under a no-vision and a vision condition, the latter serving as a base-line condition. It was found that movement time and trajectory size of acceleration and deceleration phases of a stroke movement increased under no vision, the magnitude of which depended on letter type. Letter e, with a smaller size and more frequently used in Dutch writing than letter l, was less affected by the no-vision condition. Although, close examination of downstrokes produced in later letter positions of the sequence revealed that the acceleration as compared to the deceleration phase took proportionally less time, the general finding was that increments in time and size proved to be equally distributed across entire stroke movements. PMID- 8475771 TI - Changes in motor planning during the acquisition of movement patterns in a continuous task. AB - Changes in the planning and execution of movements were studied as a function of practice on a continuous motor task. Twelve subjects learned to move a pen through a cut-out square and maze patterns with their eyes closed. Maze patterns consisted of six, eight, ten, or twelve segments that were connected by intersections. Task performance was studied during six blocks. Although the mazes could be traced continuously in a clockwise direction, selecting a wrong turn at an intersection resulted in coming to a dead end. Performance at intersections was analyzed by determining the number of correct (and incorrect) turns following mechanically forced stops and the number of correctly planned and executed turns without any halt. In addition, movement time and pause duration were analyzed. With practice an increase in the number of correctly executed turns indicated that subjects gradually learned to group segments into chunks of increasing size. It was found that up to eight segments could be organized and executed as a single unit. Finally, with practice a non-linear performance improvement was found, suggesting that the learning process proceeded through qualitatively different learning stages. It is concluded that within five minutes subjects gradually changed their movement strategy from a sequential, trial-and-error mode in which planning and execution occurred segment by segment, to a mode in which concurrent planning was realized, i.e. in which the planning of oncoming segments occurred concurrently with the execution of segments. PMID- 8475772 TI - Exploitation of elasticity as a biomechanical property in the production of graphic stroke sequences. AB - In the present study we report several findings which indicate that subjects exploit elasticity of muscles and tendons as a biomechanical property of the motor system in the execution of graphic stroke sequences. The drawing movements of 15 right-handed subjects were analyzed, who copied a geometrical pattern consisting of four line segments. Three of these segments were connected by an acute and an obtuse angle. A first analysis concerning stroke-direction preferences shows that subjects tended to produce final strokes in preferred movement directions and obeyed an end-state stability constraint. Subsequently, we analyzed the copying movements with respect to (1) pauses at acute and obtuse angles, (2) local deviations in angle size, and (3) size variations of the strokes surrounding the angles. The results reveal a higher incidence of pauses at obtuse than at acute angles. Furthermore, a local sharpening of angles was found which was most pronounced at obtuse angles. Finally, systematic size variations of the strokes surrounding the angles were found. The results are considered to reflect the functional use of elasticity during task performance. It is concluded that biomechanical properties of the motor system significantly influence higher-order preparatory processes involved in multi-trajectory control. PMID- 8475773 TI - Effects of lexicality and trigram frequency on handwriting production in children and adults. AB - Recent studies of handwriting have shown that linguistic variables, such as phonology or lexicality, influence various aspects of the production of letter sequences. Following a previous experiment, in which a facilitation effect of words over pseudowords has been documented both in children and in adults, an experiment is reported concerning the effect of lexicality and of trigram frequency on handwriting production at different levels of handwriting mastery. In this experiment, 8- to 12-year-old children and adults were asked to write words, pseudowords ending with a frequent trigram, and pseudowords ending with a nonfrequent trigram. Results show that in adults there is a facilitation effect of words over pseudowords and of frequent trigrams over nonfrequent trigrams. In children, no clear effect of lexicality or trigram frequency could be observed. Developmental trends show that major changes in children's handwriting occur between 8 and 10 years, whereas only minor modifications are observed between 10 and 12 years. PMID- 8475774 TI - Analysis of actual and mental movement times in graphic tasks. AB - This paper reports on a study of movement times and movement time variability of graphic gestures which were executed either physically or mentally. The results revealed that temporal parameters for actual as well as mental graphic movements in the same subject and for the same hand were very similar, irrespective of the writing amplitude. It is suggested that the programming of motor acts, whether they are physically executed or only virtually, share to a considerable extent the same timing mechanism. PMID- 8475775 TI - Evaluating the special role of time in the control of handwriting. AB - Claims that time has a special role in the control of writing and the specific claim that writing time is absolutely invariant across changes in writing size are evaluated in two experiments. The first examined writing time for 24 undergraduate subjects who produced the string eyleyl with the dominant hand or arm in blocked repetitions having different vertical size targets. These variations produced small but systematic changes in writing time. The second experiment explored whether the small range of writing-time variation observed in experiment 1 was due to structural or strategic limitations. This experiment showed, for four undergraduate subjects, that writing time can be varied precisely across a wide range (0.6 to 1.66 of 'normal') while maintaining shape and vertical size constant. Taken together, these experiments suggest that, although relative stroke timing is approximately maintained, absolute timing is not critical to writing. The limited range of writing times typically observed should, rather, be ascribed to a strategic gradient that, along with other influences, broadly defines preferred writing times. This paper also describes a new application of Generalized Procrustes Analysis of shape, and this procedure is applied to the trajectories generated in both experiments. Although several small failures are noted, these analyses generally confirmed previous claims that shape is invariant across changes in writing time, size, and writing with the hand versus the arm. This result is a necessary buttress to the conclusions just described. Shape variability was also assessed in these analyses. This variability soared as writing time was reduced from normal, but showed only a small, insignificant increase as writing time was increased from normal. There were also small, predictable changes in spatial variability across changes in size and effector. PMID- 8475776 TI - Generalized representation of handwriting: evidence of effector independence. AB - Previous analyses of writing data have provided qualitative evidence of temporal and spatial similarities across muscle effectors. In order to further explore the notion of effector independence in handwriting a single case study approach was adopted that employed quantitative analyses. A left-handed individual who lost his left hand and forearm in an automobile accident and wore a myoelectric arm was tested. After his accident he learned to write with the right hand developing this skill for 8 years. Once he was fitted with the myoelectric arm he began again to write with the left hand. Thus, the acquired writing patterns of both hands reflect two well-learned skills which utilize different muscle effectors. Wright's NAME-EQUATION paradigm (1990) was utilized which required the subject to write his name and the equation X + Y = Z with the dominant, non-dominant hand and the elbow of the dominant arm. A control subject was also tested. For the subject wearing a myoelectric arm (primary subject), kinematic and handwriting analysis revealed astonishing similarities between the different effectors tested. For the control subject, the obtained results showed that as the effectors changed so did the handwriting kinematics. The collective findings support the hypothesis that motor programs, the directives that guide skilled movement, can be generalized across different effectors, but only after considerable practice. PMID- 8475777 TI - Invariant properties between stroke features in handwriting. AB - A handwriting pattern is considered as a sequence of ballistic strokes. Replications of a pattern may be generated from a single, higher-level memory representation, acting as a motor program. Therefore, those stroke features which show the most invariant pattern are probably related to the parameters of the higher-level representation, whereas the more noisy features are probably related to the parameters derived at the lower levels (top-down hierarchy). This hierarchy of invariances can be revealed by the signal-to-noise ratio (SNR), the between-parameter correlations, and the between-condition correlations. Similarly, at the higher level a sequence of strokes may act as a unit from which individual strokes are derived (sequence hierarchy). This hierarchy of invariances can be revealed by the between-stroke correlation, which forms a weaker criterion than rescalability, which has been rejected mostly. Previous research showed that vertical stroke size has higher SNRs and higher between condition correlations than stroke duration or peak force, whereas the latter two features were also negatively correlated. This suggested that vertical stroke size is a higher-level parameter than the other two. The present research largely confirmed this top-down hierarchy and even for upstrokes and downstrokes separately. Downstrokes were more invariant than upstrokes in terms of vertical stroke size. However, contrary to the vertical stroke size, the horizontal stroke size was not invariant. Both vertical and horizontal sizes showed substantial between-stroke correlations. In contrast, the stroke durations did not show any between-stroke correlations. This suggests that stroke segmentation is reliable in spite of the discrete sampling of the handwriting movements. PMID- 8475778 TI - Looking at handwriting generation from a velocity control perspective. AB - This paper presents a model that explains the origin of the asymmetric bell shaped velocity profiles generally observed in handwriting and other rapid movements. Applying the central limit theorem to describe the converging behavior of a sequence of dependent neural and muscular networks, it is shown that velocity profiles can be described by log-normal curves. An analysis-by-synthesis experiment is reported to support the model and to specify its mathematical implementation. Practical implications of this approach are discussed at the end of the paper to provide an analytical definition of a stroke, to clarify the concept of fluency and to suggest a powerful method for segmenting complex movements, particularly cursive script. PMID- 8475779 TI - In vitro effect of ascorbic acid on neutrophil-endothelial cell interaction. AB - The effect of different concentrations (0.06, 0.6 and 6.0 mmol/L) of ascorbic acid on neutrophil-endothelial interaction was studied using an in vitro model of human umbilical cord vein endothelial cells and human neutrophils. The aim of the study was to determine changes in chemiluminescence response of neutrophils during adherence to endothelial cells. Because adherence of neutrophils to endothelial cells is an essential component in inflammatory processes leading to endothelial cell injury, the influence of ascorbic acid on adherence and endothelial cell injury have been investigated. Production of oxygen-derived metabolites, measured by chemiluminescence response of neutrophils, decreased significantly in the presence of 6 mmol/L ascorbic acid during coincubation of neutrophils and endothelial cells (p < 0.025). The adherence of neutrophils to endothelial cells was significantly decreased at a concentration of 6 mmol/L (p < 0.0005). The inhibition of neutrophil adherence to endothelial cells was correlated with a diminished neutrophil-mediated endothelial cell injury during incubation with 6 mmol/L ascorbic acid (p < 0.0005). The present results indicate that ascorbic acid might exert a protective effect on neutrophil-mediated endothelial cell injury by decreasing adherence of neutrophils to endothelial cells and by scavenging reactive oxygen metabolites. Moreover, the current investigation points to probable protective effect of ascorbic acid on oxidant mediated cell damage in diseases (e.g., Adult Respiratory Distress Syndrome). PMID- 8475780 TI - Determination of serum oxalate using peroxyoxalate chemiluminescence of free oxalic acid. AB - We describe a new sensitive and specific method for determination of oxalate in human serum. By using the chemiluminescence decay of monoperoxyoxalic acid very low concentrations of oxalate (200 nmol/L) can be determined. The mean serum oxalate level in apparently healthy controls was 14.5 +/- 8.5 mumol/L. Supplementation of ascorbic acid leads to an increase in serum oxalate level. While serum oxalate concentrations of calcium oxalate stone formers (x = 16.4 +/- 9.8 mumol/L) are not significantly different from the control group, an extreme increase of serum oxalate is evident in haemodialysis patients. The serum oxalate concentration decreased during dialysis treatment from 141.4 +/- 32.1 mumol/L to 36.4 +/- 12.7 mumol/L. PMID- 8475781 TI - Flow injection chemiluminescence study of acridinium ester stability and kinetics of decomposition. AB - Decomposition of phenyl acridinium-9-carboxylate is monitored using electrogenerated chemiluminescence in a flow system. The formation of the pseudobase from the acridinium ester [AE] is described by rate = k'1[AE] + k''1[AE][OH-]0.5, where k'1 = 0.020 +/- 0.006 s-1 and k''1 = 2.1 +/- 0.8 (L/mol) 0.5 s-1. Irreversible decomposition of the pseudobase is described by rate = k'2[AE][OH-], where k'2 = 20.1 +/- 3.8 (L/mol s). These kinetic equations, plus measurement of variation in emission intensity for constant acridinium ester concentration, are used to predict the resulting emission intensity v. pH behaviour given various contact times (in the 0.25 to 25 s range) for the acridinium ester to be in an alkaline solution prior to initiation of the chemiluminescence reaction. PMID- 8475782 TI - Separation of pH, dilution, ionic strength and chemical matrix effects for biological monitoring of urines with the Microtox test using nicotine, cotinine and reference urines. AB - The aim was to investigate the factors influencing light emission from Photobacterium phosphoreum in the Microtox test to interpret bioassay results for urine. Four reference urines were assessed as reference materials for the bioassay. Nicotine and cotinine were investigated as urinary markers for tobacco exposure. The optimum luminescence conditions were: 1.85%-3.25% NaCl, 0.33-0.58 mol/L ionic strength, and pH 5.8-6.7. Low pH values and high concentration of toxic trace metals were important factors in this study. Unexpected toxicity for a Standard Reference Material was attributed to zinc contamination. Nicotine and cotinine together exhibited antagonistic effects in 2% saline but this could not be observed in the urines because of substantial urine toxicity. Thus practical urinary biological monitoring with the Microtox test necessitates excretion of metabolites and compounds that are much more toxic than the urine components. Also, separation of the effects of physical factors like pH, ionic strength and dilution is essential before chemical toxicity effects can be assigned. This is the first report of Microtox EC50 values for nicotine and cotinine. The results have application to environmental samples since analyses are often uncontrolled relative to pH, ionic strength and dilution. PMID- 8475783 TI - [Significance exercise-induced ST elevation in patients with myocardial infarction]. AB - In 52 patients with previous myocardial infraction, 49 men and 3 women (mean age 56 +/- 7.1 years) the significance of ST-segment elevation during the stress test, was evaluated. Of the 52 patients 15 (29%) showed St-segment elevation and 37(71%), showed no alteration of the ST-segment. Extension of coronary disease, degree of obstruction, wall motion abnormalities and the presence of residual ischemia were evaluated by coronary angiography, technetium-99M pyrophosphate imaging and exercise TL-201 scintigraphy. From the results of the study one may conclude that, in patients with previous myocardial infraction exercise, ST segment elevation is a consequence of sub-occlusion of the left anterior descending coronary artery with severe ventricular dysfunction either in patients with one or multiple vessel disease. PMID- 8475784 TI - [Tomodensitometry and radioisotopic methods in the study of unilateral lung hyperlucencies of vascular origin]. AB - Among the causes of the radiological entity known as unilateral or total hyperlucent lung is the decreased blood flow in the lungs. Unilateral and total hyperlucent lung results, among other factors, from the decreased intrapulmonary blood flow. Classically, the diagnosis and haemodynamic evaluation of these situations were usually made through invasive methods: right heart catheterism to perform angiopneumography and pressure evaluations as well as oximetry at several levels of the vascular network, thoracic aortography eventually associated with selective arteriography to detect the abnormalities of the systemic thoracic circulation. In this context, the authors propose for the diagnosis and study of this pathology, a new non-invasive methodology. In order to achieve this propose, we studied 8 patients, all of them performed clinical and laboratory evaluations, chest chi-ray, electrocardiographic and functional respiratory exams, as well angiopneumography, thoracic aortography tomodensitometry including qualitative (to study the lung arterial vasculature) and quantitative (to evaluate CT density of each lung in Hounsefield unit and two radioisotopic tests, including a ventilation/perfusion study with 133 chi e and HAM-99mTc, through an original software--four parameter histograms allowing simultaneous information of ventilation and perfusion at the pixel level and estimation of the V/Q; the other is the pulmonary gating through which it is possible to identify and quantify the arterio-arterial shunts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475785 TI - [Medical research financing]. PMID- 8475786 TI - [Medical research in Portugal: the geniuses and the structures, the myths and common sense]. AB - There was recently a growth in the funds allocated directly to scientific programs and projects and in particular to infrastructures (buildings and large pieces of equipment). It is very likely that this investment will continue to grow as a result of the development policies of the EEC applied to its less developed members. The recent experience with the Science Program, the main factor in this evolution, has demonstrated that the bottleneck in our scientific development is at the level of the allocation of funds (management). Hence, the nonrealistic Regulations of the Program, the allocation of funds to ghost institutions and the inability to distribute the funds allocated to the Program. The Program was conceived based on problem oriented and not on research oriented strategies. In the case of medical research this choice is not supported by the recent history of research in this area or by the experience of countries such as the UK or the USA. Funding of medical research in this country should be based on the identification of a talented scientist with a good research program and on an inventory of the productivity, potentialities and needs of existing institutions. We should seek the support of foreign scientists and of Portuguese scientists living abroad for the technical evaluation of projects but they should not be asked to provide global strategies of investment in Portuguese science. PMID- 8475787 TI - [Errors in medicine]. AB - The author discusses the different kinds of errors that may be committed in clinical practice. The socioeconomic and professional factors that make doctors particularly vulnerable are briefly reviewed. PMID- 8475788 TI - [Superior mesenteric artery syndrome. Report of 2 clinical cases]. AB - The authors describe two cases of the superior mesenteric artery syndrome. The diagnosis was made by radiology and both were treated surgically. They emphasize the most relevant symptoms (epigastric pain and vomiting) and the characteristic radiological signs which permit the diagnosis (marked to-and-fro peristalsis in the duodenum with extrinsic compression of the third part and proximal dilatation ending abruptly). Although the conservative measures are sufficient in most cases, those presented in this paper, both needed surgery. PMID- 8475789 TI - Age- and gender-related changes in body composition in Japanese subjects. AB - Age-dependent changes in body composition, namely a decrease in bone mass and lean mass and a reciprocal increase in fat mass, are often observed in normal populations. The recent development of dual-energy x-ray absorptiometry (DXA) made it possible to analyze bone mineral content (BMC), fat mass (fat), and lean body mass (LBM) more precisely and easily. We measured BMC, fat, and LBM in Japanese subjects by DXA to describe the changes in body composition with aging in the Japanese population. A total of 34 female (aged 20-74) and 34 male (aged 18-78) volunteers were divided into three groups according to their age: young (18-22 years), middle-aged (39-48 years), and old (61-78 years). Mean values for body height (BH), body weight (BW), and body mass index (BMI) of the subjects were very similar to Japanese normative values. The BMI of the middle-aged group was the highest of all groups of both sexes. BMC decreased significantly with aging in females but not in males. A decrease in LBM and a reciprocal increase in fat were found between young and middle-aged males but not in females. The correlation between BMC and LBM tends to be greater in males than in females. On the other hand, the correlation between BMC and fat was greater in females than males. These results demonstrate the age- and gender-related difference in body components in Japanese subjects. DXA may be useful for the analysis of body composition in different age and sex groups. PMID- 8475790 TI - Expression of alpha v and beta 3 integrin subunits in rat osteoclasts in situ. AB - Recent findings suggest that the vitronectin receptor, a member of the integrin family, plays an important role in the attachment of osteoclasts to bone matrix. We report here the localization by in situ hybridization of the mRNA for the alpha and beta subunits of the vitronectin receptor in rat bone sections. To generate the rat-specific RNA probes used in this study, we cloned cDNA fragments of integrin chains alpha v, beta 3, and beta 5 by the polymerase chain reaction from rat cDNA. These fragments share 86-91% homology with the respective human sequences. In situ hybridization localized the alpha v and beta 3 mRNAs to regions undergoing extensive bone resorption. The histologic appearance and prestaining of bone sections for tartrate-resistant acid phosphatase (TRAP) indicated the presence of these mRNAs in osteoclasts. These observations support immunohistochemical findings that osteoclasts express high levels of the vitronectin receptor, confirm the identity of this receptor as integrin alpha v/beta 3, and suggest that osteoclasts may actively synthesize these molecules. PMID- 8475792 TI - Recombinant human transforming growth factor beta 1 modulates bone remodeling in a mineralizing bone organ culture. AB - TGF-beta 1 increases cell proliferation and collagen synthesis in osteoblast-like cells and bone organ cultures. However, the effects of TGF-beta 1 on bone resorption remain contradictory. Therefore, the exact role that this growth factor plays in the process of bone remodeling is still not clear. We studied the effects of recombinant human TGF-beta 1 (rhTGF-beta 1) on bone formation and resorption in a mineralizing bone organ culture system. Parietal bones from 20 day-old fetal rat calvariae were cultured up to 7 days in serum-free BGJb medium. They responded to a 1 day pulse or continuous treatment of rhTGF-beta 1 with dose dependent increases in dry weight, [3H]thymidine ([3H]TdR) incorporation, and collagen synthesis. In contrast, rhTGF-beta 1 reduced the calcium content of the bones. This is not due to increased bone resorption but rather to failure of calcium deposition. The following responses occurred at 1 nM rhTGF-beta 1. Dry weight was increased 25-50% after 6 days in culture. DNA synthesis was increased to a maximum at day 1, reaching twofold of the control level. Adding hydroxyurea at day 0 reduced [3H]TdR incorporation in rhTGF-beta 1 treated bones to 20% of the control and indomethacin abrogated the increase in [3H]TdR stimulated by rhTGF-beta 1 to the control level. Both treatments completely blocked the increase in dry weight induced by rhTGF-beta 1 at day 6. rhTGF-beta 1 stimulated collagen synthesis to reach its maximum at day 2, with a twofold increase in [3H]proline incorporation. Basal alkaline phosphatase activity fell continuously in culture, reaching 35% of day 0 level at day 6. Enzyme activity was not altered by rhTGF-beta 1. Morphologic observations by light and electron microscopy confirmed these findings. In summary, rhTGF-beta 1 altered bone remodeling by increasing organic components and decreasing calcification in a mineralizing bone organ culture system. PMID- 8475791 TI - Longitudinal study of bone mass in end-stage renal disease patients: effects of parathyroidectomy for renal osteodystrophy. AB - The effectiveness of parathyroidectomy (PTHX) for the control of secondary hyperparathyroidism was assessed in 46 adult end-stage renal disease (ESRD) patients whose bone mineral content at the midshaft and distal radius was measured using single-photon absorptiometry (SPA) every 6 months before and after the surgery. They were compared to 46 age-, race-, and sex-matched ESRD patient controls who had not undergone surgery but who had had at least five SPA studies at similar intervals. Presurgery midradius bone mass was significantly lower for PTHX patients compared to controls. Comparing changes in bone mass of PTHX patients across surgery to controls in comparable time periods showed that PTHX patients lost significantly less bone mass after surgery. Similar results were obtained when rates of change in bone mass were evaluated. When patient characteristics were examined, the effect of surgery was found to be diminished in elderly patients and in oophorectomized patients. It is concluded that PTHX can have a salutary effect on renal osteodystrophy in the appendicular skeleton, but factors other than bone mass also need to be considered in identifying those patients who will benefit from surgery. PMID- 8475793 TI - High-dose estrogen inhibits bone resorption and stimulates bone formation in the ovariectomized mouse. AB - In this study, we have investigated estrogen's capacity to regulate bone formation and resorption in the ovariectomized mouse, evaluating the dose and site dependence of estrogen action on bone modeling and remodeling surfaces. To quantitate bone resorption, the skeletons of fifty 8-week-old Swiss-Webster mice were prelabeled with [3H]tetracycline (3H-T) before initiation of treatment protocols. Ovariectomies (OVX) and sham surgeries were performed 3 days after the final 3H-T injection, and the animals were assigned to treatment groups and injected once per week for 4 weeks with one of the following doses of 17 beta estradiol (E2): sham/oil vehicle (SV), OVX/oil vehicle, OVX/50 micrograms E2, OVX/250 micrograms E2, and OVX/500 micrograms E2. To assess bone formation, fluorochrome labels were administered 9 and 2 days before sacrifice. At the conclusion of the 4 week protocol, the femora and thoracic vertebrae were removed to quantitate the levels of bone resorption based on the skeletal retention of 3H T. The tibiae were excised for histomorphometric evaluation of the proximal metaphyses and middiaphyses. Indicative of increased bone resorption, vehicle treated OVX animals had significantly reduced levels of 3H-T in femora and vertebrae compared to SV mice. This result was consistent with histomorphometric data showing a 49% decrease in cancellous bone area of the proximal tibiae in the OVX/oil-treated group. Treatment of OVX animals with 50 micrograms E2 was sufficient to maintain 3H-T levels in vertebrae at SV values, with higher E2 doeses leading to a dose-dependent increase in the retention of 3H-T at this site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475794 TI - Bone formation periods studied with triple tetracycline labels in women with postmenopausal osteoporosis. AB - In adult cancellous bone, cyclic remodeling occurs in discrete locations (BMUs, or basic multicellular units). Some aspects of these remodeling cycles are still not clear. Only about half the osteoid surface normally has tetracycline labels; the remainder is thought to be immature or in a resting phase. This study was designed to test the assumption that pauses occur during the bone formation periods. Iliac crest bone biopsies were performed in 84 women with postmenopausal osteoporosis. The subjects were given three tetracycline labels; the middle label had a distinctive color. The osteoid surface was 10 +/- 6% of the bone surface; the range was 0.6-24.4%. The mineralizing surface was 42 +/- 26% of the osteoid surface. Immature osteoid was 7.6 +/- 5.3% of the osteoid surface. There were no BMUs with the first and third tetracycline label but without the middle demeclocycline label. The expected length of double 1-3 label, based on an assumption that unlabeled mature osteoid was temporarily in a resting phase, was significantly higher than the observed length (68 +/- 77 microns/mm2 tissue area versus 0, p < 0.0001). The mean active formation period was 77 +/- 16 days calculated by standard methods but was only 55 +/- 26 days when calculated by label escape (p < 0.001). The correlation coefficient between these two methods was only modest (r = 0.27, p < 0.01). The failure to find any double 1-3 labels despite abundant triple labels provides strong evidence against the presence of pauses in bone mineralization between 3 and 34 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475795 TI - Bone mineral density and parameters of bone metabolism in patients with acromegaly. AB - To assess the effect of chronically elevated plasma growth hormone (GH) levels on bone metabolism and bone mineral density (BMD), 16 patients (10 females and 6 males) with a mean age of 49.1 +/- 13.2 years (range 33-68) with active acromegaly were studied and compared to a control group of 16 sex- and age matched subjects. BMD of the lumbar spine and two different sites of the proximal femur were measured by dual-energy x-ray absorptiometry (Norland XR-26). In the acromegalic patients the mean plasma GH concentration was 30.1 +/- 11.1 micrograms/liter, and the mean plasma somatomedin C (SMC) concentration was 6.5 +/- 1.5 U/liter. Mean serum osteocalcin (OC) levels (14.3 +/- 1.1 versus 7.2 +/- 0.4 ng/ml, p < 0.001) as well as the urinary hydroxyproline excretion (OHP; 8.8 +/- 1.4 versus 2.7 +/- 0.3 mg, p < 0.0001) were significantly higher in the acromegalic patients than in the control subjects. In the acromegalic patients BMD was significantly elevated in the two examined regions of the proximal femur, that is, the femoral neck (1.06 +/- 0.05 versus 0.86 +/- 0.03 g/cm2, p < 0.05) and Ward's triangle (0.92 +/- 0.06 versus 0.76 +/- 0.03 g/cm2, p < 0.02), whereas the BMD of the lumbar spine was not significantly different from that of control subjects. Among the patients with acromegaly a significant positive correlation between serum OC concentrations, on the one hand, and urinary OHP excretion (r = 0.7, p < 0.004) as well as BMD in the proximal femur (r = 0.64, p < 0.007), on the other hand, could be observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475796 TI - CGRP radioreceptor assay: a new diagnostic tool for medullary thyroid carcinoma. AB - The quantitative analysis of immunoreactive calcitonin (iCT) is the assay of choice for diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC). However, in a small percentage of patients with MTC or C cell hyperplasia (CCH), basal and stimulated iCT levels may not be significantly elevated. In these patients, calcitonin gene-related peptide (CGRP) radioreceptor assay (RRA) can be used complementary to immunoassay for CT (or katacalcin) for prompt diagnosis of MTC and CCH. CGRP RRA is a robust, rapid, sensitive, and specific determinant of "receptor-recognized" CGRP (RR-CGRP; intact molecule of CGRP) either in plasma or in tissue extracts. Plasma RR-CGRP levels rose > 100% 2-5 minutes after stimulation with intravenous pentagastrin (calcium or oral alcohol) (p < 0.001), whereas iCGRP levels were raised to a lesser degree (p < 0.01). In six patients who had a false positive iCT response after pentagastrin or had raised basal iCT levels measured with a two-site immunoradiometric assay, RR-CGRP showed only a minimal change. On the other hand, in patients with CCH (true positive, n = 8), iCT was increased by only 40% after pentagastrin but RR-CGRP levels rose by 140% (p < 0.001). No change in iCT or RR-CGRP levels in plasma were detected in healthy normal volunteers after administration of pentagastrin. Therefore, in addition to the plasma iCT levels, RR-CGRP would resolve some of the difficult diagnostic problems associated with MTC and likely improve the specificity and sensitivity of identifying CCH. PMID- 8475797 TI - Regulation of expression of the chondrocytic phenotype in a skeletal cell line (CFK2) in vitro. AB - We have examined in vitro the spontaneous and regulated expression of phenotypic characteristics associated with differentiated chondrocytes in an established skeletal cell line (CFK2) derived from fetal rat calvariae. Extended culture of CFK2 cells resulted in the appearance of glycosaminoglycans and type II collagen in the cell layer in association with the formation of focal nodes of cells. In addition, induction of mRNA-encoding link protein, cartilage-specific proteoglycan core protein, and thrombospondin was observed in the differentiated population (dCFK2 cells). The expression of these mRNAs was present for at least two passages after subculturing the dCFK2 cells. The dCFK2 cells also demonstrated enhanced parathyroid hormone (PTH)-stimulated adenylate cyclase activity. Proliferation of CFK2 cells was stimulated by the peptide regulatory factors EGF and PTH and inhibited by the steroidal agents dexamethasone and retinoic acid. EGF and retinoic acid inhibited the formation of cell foci and glycosaminoglycan deposition and the expression of mRNA-encoding link protein. In contrast, PTH and dexamethasone enhanced the formation of focal cellular nodes and augmented matrix deposition and link protein mRNA expression. These studies therefore show that the CFK2 cell line can serve as a nontransformed model of rat chondrocytic cells in which both induction and regulation of the expression of cartilaginous matrix components can be observed. This line thereby provides a unique renewable source of chondrocytic precursor cells and an excellent in vitro model for evaluating temporal and environmental control of chondrocyte differentiation and cartilage matrix production. PMID- 8475798 TI - Ultrastructural immunolocalization of noncollagenous (osteopontin and osteocalcin) and plasma (albumin and alpha 2HS-glycoprotein) proteins in rat bone. AB - The high-resolution, postembedding protein A-gold immunocytochemical technique was used to visualize the distribution of two noncollagenous bone proteins, osteopontin (OPN) and osteocalcin (OC), and two plasma proteins, alpha 2HS glycoprotein (alpha 2HS-GP) and albumin (ALB), in sections of Lowicryl K4M embedded rat tibial and alveolar bone. In the primary spongiosa of the metaphysis, a seam of organic material (lamina limitans) that labeled intensely with OPN and OC antibodies was observed at the bone/calcified cartilage interface just below the zone of vascular invasion of the growth plate. With deposition of bone matrix proper by osteoblasts in this region and its subsequent mineralization, extensive areas of bone were heavily labeled with anti-OPN, anti OC, and anti-alpha 2HS-GP antibodies, where the majority of gold particles were associated with amorphous, electron-dense patches of organic material throughout the mineralized bone. In the unmineralized osteoid, substantially less labeling was observed, and where occasional mineralization loci were dispersed throughout the osteoid layer, these sometimes showed a concentration of gold particles. ALB labeling, on the other hand, was moderate and generally diffuse throughout the mineralized bone matrix and the osteoid. In alveolar bone, labeling patterns were generally similar to those found in tibial bone. Particularly striking in alveolar bone, however, was an intense anti-OPN labeling of (1) the lamina limitans at cell-lined bone surfaces, including that surrounding cell processes and osteocytes, (2) cement (reversal, resting) lines, and (3) the perilacumar matrix of some osteocytes. In summary, these data suggest that certain plasma proteins, such as alpha 2HS-GP, interact with bone matrix proteins, such as OPN and OC, at sites of tissue mineralization and that the presence of OPN in mineralized bone and at bone surfaces (lamina limitans) and cement lines has a multifunctional role, including regulation of mineralization and mediation of cell dynamics during endochondral and intramembranous bone modeling and remodeling. PMID- 8475799 TI - Protein kinase C-activating domains of parathyroid hormone-related protein. AB - N-terminal fragments of PTH-related protein (PTHrP), PTHrP-(1-34), and PTHrP-(1 40) stimulated both adenylyl cyclase and a mechanism that increases membrane associated protein kinase C (PKC) activity in ROS 17/2 rat osteosarcoma cells. There were two peaks in the PKC response to the N-terminal PTHrP fragments: one peak was obtained with picomolar and the other with nanomolar PTHrP concentrations. The PKC-stimulating picomolar concentrations of the PTHrP fragments did not detectably stimulate adenylyl cyclase, but the nanomolar concentrations did. Since a similar two-peak response of PKC activity was obtained with PTHrP-(28-34), the single, N-terminal PKC activation domain of the PTHrP is in the same 28-34 region of the molecule as that of PTH despite this region having different primary amino acid sequences in the two hormones. Unlike PTH, PTHrP has a second PKC activation domain, as indicated by the ability of picomolar concentrations of the PTHrP-(107-111) fragment to stimulate maximally membrane-associated PKC activity in the osteosarcoma cells. PMID- 8475800 TI - Volume regulation of the brain tissue--a survey. AB - Though the brain bulk has been considered to be constant in several pressure homeostasis studies, the central nervous tissue may be responsible for the accommodation of extracerebral masses exceeding the volume regulation capacity of the cerebral blood and cerebrospinal fluid. Volume buffering of the nervous tissue may even be functioning in parallel, in conjunction with the "fluid" compartments. Of the existing volume regulatory models, the following are discussed: osmotic feedback (buffering) preventing major fluid shifts in osmotic or pressure disequilibrium at the blood brain barrier (BBB), and the 4 compartment model, which under steady-state conditions can be regarded as an analogue of systemic tissue volume regulation, i.e. secretion of fluid at the BBB, bulk flow of interstitial space fluid (ISF) in the brain and absorption via the cerebrospinal fluid (CSF). The most recent data are presented, confirming that accommodation of space occupation by the nervous tissue is achieved via shrinkage of the extracerebral fluid (ECF), while the cell volume remains relatively constant. These findings confirm Hakim's classical hypothesis, based on biomechanical considerations, that the brain behaves like a sponge. The data presented in this survey point to a more general hypothesis: the brain interstitial space can vary in volume according to physiological and pathological stress, within certain bounds this being a reversible process which does not affect brain function. The potential role of the central neuro-endocrine system in brain volume regulation is discussed. Vasopressin (AVP) and atriopeptin (ANP) probably, function within the brain via a paracrine mechanism, as physiological regulators of brain cell and ISF volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475801 TI - Penetration of fusidic acid into human brain tissue and cerebrospinal fluid. AB - Penetration of fusidic acid into brain tissue in six patients and cerebrospinal fluid in seven patients was determined. Tissue samples, taken during surgery revealed drug levels at about 7% of simultaneous serum concentrations. In contrast, cerebrospinal fluid concentrations were below 1% of serum levels. Since serum- and tissue levels of fusidic acid were far above the minimal inhibitory concentration (MICs) of staphylococci and streptococci, and since it has a long serum half-life of about 10 hours, it is a promising candidate for prophylaxis in neurosurgery. PMID- 8475803 TI - Selective angiography for early aneurysm detection in acute subarachnoid haemorrhage. AB - In a consecutive series of 312 surgical aneurysm cases more than 90% of the patients reached neurosurgical expertise within 48 hours from bleeding. Computed tomography permitted prediction of the assumed rupture site based on blood clot location in the majority (86%) of cases. This target vascular territory was usually investigated by selective angiography and in 9 out of 10 patients an aneurysm, ultimately shown to be the correct source of bleeding, was demonstrated. In 14% of the cases the source of bleeding could not be established thus calling for complete four vessel studies. It is concluded that limited angiographic studies are compatible with preserving a high surgical standard in cases unequivocally exhibiting a localizing clot pattern on the CT scan. Though suboptimal in a general sense, incomplete vascular studies, if four vessel angiography is not obtainable without delay or risk, should not delay earliest possible clipping of ruptured aneurysms to avoid the devastating effects of recurrent bleeds. PMID- 8475804 TI - Interest and necessity of combined neuroradiological and neurosurgical treatment in some cases of dural arterio-venous fistulae. AB - The authors report 3 observations of dural arterio-venous fistula cured by combined neuroradiological and neurosurgical intervention. In the first case, the shunt affected the left lateral sinus. Repeated embolizations failed whilst intracranial hypertension developed, as a consequence of flux in the opposite lateral sinus and in the sagittal sinus. Surgical intervention, consisting in isolation of the transverse sinus, led to complete cure, after a one month delay. In the second case, the shunt was adjacent to the sagittal sinus, right parietal, and had led to an intracerebral haematoma, by rupture of an arterialized cortical vein. Embolizations alone could not cure the fistula which therefore had to be excised. In the third case, the shunt was located in the falx, at the parieto occipital junction, and was responsible for arterialization of cerebral veins in the right parieto-occipital region. For this reason, after failure of endovascular treatment, the fistula was coagulated, with subsequent complete cure. These three cases illustrate the different types of drainage of such arterio-venous fistula, and their corresponding neurological symptoms and signs, complications and risks, that required a radical-not only clinical, but also anatomical-cure. This aim was achieved when embolizations were accompanied by direct surgical attack. PMID- 8475802 TI - Stereotactic aspiration of brain abscesses: is this the treatment of choice? AB - Despite a reduction in the mortality of patients with brain abscess since the introduction of the computed tomography (CT) scanner, controversy persists as to the preferred method of treatment for this condition. Eleven patients were treated by CT guided stereotactic aspiration of pus and appropriate antibiotic therapy. A total of 14 aspirations were performed. Ten abscesses were supratentorial and one was in the posterior fossa. In 9 patients a bacterial cause was identified while in 2 a fungus was identified. A good outcome was achieved in 7 patients but 3 patients died. Another elderly patient remains disabled at home. The deaths occurred in severely systemically ill patients with poor conscious levels on admission. Only one patient has epilepsy, controlled with anticonvulsants while another has not had further seizures since abscess treatment a year ago. Stereotactic aspiration should be considered the treatment of choice in all but the most superficial and largest cerebral abscesses, although the mortality of this condition in the severely ill remains high. PMID- 8475805 TI - Unruptured intracranial arteriovenous malformations with hereditary haemorrhagic telangiectasia. Neurosurgical treatment or not? AB - Clinical decision analysis is applied to treatment decisions for three patients with unruptured familial intracranial arteriovenous malformations (AVMs) in association with hereditary haemorrhagic telangiectasia (HHT). The grades of the AVMs--according to Spetzler--were 1-0-0 (two patients aged 12 and 14) and 2-0-1 (one patient aged 43). The AVM in one patient (graded 1-0-0) was operated on without sequelae. In the decision analysis, life expectancy is used as an outcome measure, with and without quality of life adjustment and discounting for time preference. It is concluded that neurosurgical treatment is the optimal strategy for all three patients. Because no conclusive data are available concerning the natural history and neurosurgical treatment of unruptured AVMs, we recommend the prospective application and testing of AVM grading systems. General treatment guidelines balancing the lifetime risk of haemorrhage, risk of incomplete extirpation and surgical mortality and morbidity are given. The analysis suggests that patients with low-graded AVMs which have not bled should be treated surgically, unless they are older than 60 years and have an increased risk of incomplete extirpation. PMID- 8475806 TI - "Z" flow hydrocephalus shunt, a new approach to the problem of hydrocephalus, the rationale behind its design and the initial results of pressure monitoring after "Z" flow shunt implantation. AB - The over-drainage of CSF after shunt implantation, particularly when the patient is in the vertical posture, is well documented. Problems associated with it are negative pressure syndrome (postural headache and postural irritability), abnormal skull size, craniosynostosis and subdural haematoma. The pressure gradient in the vertical position between the cranial cavity and the right atrium is 15 to 20 cm of water and between the cranial and peritoneal cavity it is 25 to 32 cm of water and both these are much higher than those needed for the optimum functioning of a conventional shunt. The need, therefore, has been for a self regulating device that can adjust itself to any change of posture from horizontal to vertical and vice versa and regulate the flow of CSF from the cranial cavity. "Z" Flow hydrocephalus shunt system has this in-built self-regulating mechanism to prevent over drainage of CSF and the resultant abnormal low pressure in the cranial cavity. The rationale behind the functioning of "Z" Flow hydrocephalus shunt system has been discussed, its design has been described and illustrated and the results of pressure monitoring after Z Flow shunt implantation in five adult patients have been detailed. As the opening pressures of the "Z" Flow shunt system are 15-29 cm of water, it has been found to prevent over-drainage of CSF and maintain intraventricular pressure within normal limits. PMID- 8475807 TI - Conservative management of epidural haematomas. Prospective study of 15 cases. AB - Conservative management of epidural haematoma (EDH) depends on a balance between expansion and resorption rate of the clot. 15 patients with EDH whose CT scans demonstrated a small EDH and were asymptomatic or with minor symptoms or with a delayed diagnosis were treated conservatively. The thickness of haematoma ranged between 4.9-40.8 mm. In two patients, the haematoma extended from the posterior fossa to the supratentorial region. In 7 patients, additional intracranial pathology was detected. None of the patients had neurological deterioration on follow up. The second CT was performed on second day at the earliest, in fourth week at the latest. We conclude that the patients with EDH who are neurologically stable during the first 24 hours after trauma, with small EDH and with minor or no symptoms or signs, might be candidates for conservative management. An absolute precondition for conservative management is close supervision of the patient. PMID- 8475808 TI - Intra-operative transluminal angioplasty of the supra-aortic vessels. AB - Intra-operative transluminal angioplasty of supra-aortic vessels was performed in 9 patients. All subjects had lesions which were considered difficult or impossible to operate upon. In 2 patients a proximal occlusion of the left subclavian artery was dilated. Seven subjects showed severe stenoses of the supra aortic vessels: common carotid artery: 1, internal carotid artery: 2, external carotid artery: 1, external carotid artery prosthetic graft: 1, brachiocephalic trunk: 1, vertebral artery: 1. All patients suffered from symptoms which corresponded to the site of the lesions in question. Intra-operative angioplasty was primarily successful in all 9 patients. Re-occlusion occurred within a few days in both patients who underwent angioplasty of the subclavian artery. Six of the seven subjects with stenotic lesions remained free of symptoms and of restenosis. In the case of dilatation of a prosthetic graft of the external carotid artery asymptomatic occlusion developed within 8 weeks. In selected cases intra-operative angioplasty is a potentially valuable alternative in the treatment of surgically inaccessible lesions of the supra-aortic vessels. PMID- 8475809 TI - Studies on supratentorial subdural bleeding using a porcine model. AB - A porcine model for an acute lethal arterial subdural bleeding in man is presented. Blood from the abdominal aorta was led via an electronic drop recorder into a collapsed intracranial subdural rubber balloon. Systemic arterial pressure (SAP), two intracranial pressures and 6 other vital parameters were monitored continuously in spontaneously breathing (n = 4) and mechanically ventilated (n = 4) pigs. In both animal groups bleeding caused an immediate rise in intracranial pressures (ICP) with transtentorial pressure gradients developing. As a result the cerebral perfusion pressures (CPP) decreased progressively, leading to an isoelectric EEG. In spontaneously breathing animals, the pressure changes resulted in apnoea within 2-4 minutes, irregularities in heart rhythm and in a marked rise in SAP (the Cushing reaction). A final collapse of all pressures occurred after 222 +/- 68 sec at a mean bleeding volume of 10.3 +/- 1.9 ml. In contrast, in mechanically ventilated animals, the course of bleeding was less dramatic. No change in cardiac rhythm or rise in SAP appeared despite a larger mean bleeding volume (12.0 +/- 1.6 ml). Instead, SAP slowly fell, reaching a level of approximately 40 mm Hg within 1 hour, while CPP concomitantly decreased from 120 mm Hg to 15 mm Hg. The findings in this and in a parallel study are explained in terms of the intracranial volume tolerance concept (Zwetnow et al. 1986). The beneficial effect of assisted ventilation on the course of subdural bleeding is multifactorial, involving both metabolic and mechanical mechanisms. PMID- 8475810 TI - Lipid peroxide level increase in experimental hydrocephalus. AB - The aetiology of incomplete adrenergic denervation and reduction in the number and caliber of the cerebral vessels in hydrocephalus is still obscure. Stretching of the blood vessels alone is far from explaining these major vascular changes. Previous studies have shown that increased lipid peroxidation produces toxic effects on vessels. This experimental study was designed to investigate the possible aetiology of vascular changes in hydrocephalic rats with special reference to lipid peroxidation. Hydrocephalus was induced by injecting 50 mg/Kg sterilized kaolin suspension into the cisterna magna in 10 rats (Group A). A sham operation was performed for Group B. After three weeks the rats were anaesthetized and perfused transcardially. The brains were dissected, and cut to visualize the degree of hydrocephalus. The arteries of the circle of Willis were removed for light microscopic examination and the brains were kept for the measurement of lipid peroxidation levels. Light microscopic studies of cerebral arteries in hydrocephalic rats revealed spastic vessels with folding and corrugation of the lamina elastica. The level of lipid peroxidation in group A (260 +/- 9.129 nmol TBAR/gr wet tissue) was significantly higher than that of group B (106 +/- 3.59 nmol TBAR/gr wet tissue). It is suggested that vascular changes observed in hydrocephalic rats may be due to the high level of lipid peroxidation, which in turn may be the consequence of ischaemia caused by the hydrocephalus related stretching of cerebral vessels. PMID- 8475811 TI - Experimental basilar artery spasm caused by autologous blood application: effects of clot removal and topical nicardipine. AB - In 24 albino New-Zealand rabbits spasm of the basilar artery was produced by local application of autologous blood. The effects of blood and blood clot removal or topical nicardipine, each alone and in combination of both methods, were studied and compared to untreated controls. As well clot removal alone as topical application of nicardipine without clot removal resulted in some, but statistically not significant, enlargement of the spastically narrowed basilar artery. Only the combination of both methods caused a significant vasodilatation, up to almost normal diameter range. PMID- 8475813 TI - Titanium Riechert head ring for MR stereotaxy. Technical note. AB - Magnetic Resonance has become the preferred neuro-imaging modality. To fully take advantage of the high anatomical resolution the Riechert stereotactic system was adapted for use in Magnetic Resonance Stereotaxy. The head ring which until recently was made of an aluminum alloy has been replaced by an unsegmented head ring of pure titanium without changing the dimensions and fixation mode. No significant misregistration due to eddy currents has been noticed. Minor distortion induced by the titanium head ring can be corrected mathematically. Thus the geometric information is limited only by the pixel resolution of the MR image. PMID- 8475812 TI - Degenerative changes in the internal elastic lamina relating to the development of saccular cerebral aneurysms in rats. AB - In order to investigate the developmental mechanism of saccular cerebral aneurysms, changes in the internal elastic lamina at the junction of the anterior cerebral artery and the olfactory artery were electronmicroscopically studied in 6 control and 6 experimental rats undergoing ligation of the left carotid artery and branches of both renal arteries. In the control group, spontaneous destructive changes occurred on the luminal side of the internal elastic lamina and progressed from the luminal towards the abluminal side as the elastic lamina advanced to the apex. Close to the apex, these changes invaded and disrupted the whole elastic lamina. The elastic lamina was replaced by sparsely lined up lumps of elastic tissue in the walls of early aneurysmal alterations, and was atrophied and disappeared totally in the walls of aneurysmal alterations that had reached an advanced stage. These spontaneous changes were in agreement with reports in the literature and our own previous investigations. From the findings in the experimental rats it becomes likely that the aneurysmal changes in the elastic lamina are exaggerated forms of the normal catabolic metabolism. Therefore its synthesis on the abluminal side no longer balances with the catabolism on the luminal side. It is strongly suggested that aneurysmal alterations progress from the luminal towards the abluminal side of arterial walls and that the lytic process of elastase might play a role in the degenerative changes in aneurysmal development. PMID- 8475814 TI - A ruler for depth measurements during stereotactic operations. A technical note. PMID- 8475815 TI - Lipoma of the cerebral cortex: case report. AB - The first clinically diagnosed and successfully operated case of a symptomatic lipoma involving the cerebral cortex is reported. The patient presented with severe headaches and recurring focal seizures with secondary generalization. Computer tomography scan and magnetic resonance imaging suggested a left frontoparietal lipoma. After undergoing a craniotomy and tumor excision, the patient has shown resolution of headaches and seizures at 1-year follow-up. Lipomas of the cerebral cortex should be excised if symptomatic and accessible. PMID- 8475817 TI - [Variables associated with psychosocial adaptation of chronic renal patients undergoing treatment]. AB - 101 patients being treated for end-stage renal failure were studied in order to get the variables that are involved with psychosocial adaptation. Stepwise logistic regression analysis was made using the psychosocial adaptation as a dependent variable, determined by the Axis V of the D.S.M-III. 40 patients were found socially-adapted and 61 were not. Nine variables were related with the psychosocial adaptation: marital status, religious belief, education level, occupation, means of transportation to get to the treatment center, self-image before the sickness, C factor of 16 PF, the age and the evaluation of treatment by the patient. From the statistical analysis and from the interpretation of sings and values of the related variables, the influence of them on the psychosocial adaptation was demonstrated. PMID- 8475816 TI - Randomized placebo-controlled trial of single-dose antibiotic prophylaxis with fusidic acid in neurosurgery. AB - In neurosurgery, the antibiotic prophylaxis of choice has not yet been determined. The ideal drug should have an appropriate antimicrobial spectrum and favourable pharmacokinetic properties. In addition it should be nontoxic and easy to apply. We therefore conducted in 90 patients a prospective, randomized, placebo-controlled, double-blind trial in clean neurosurgery at increased risk of wound infection using a single pre-operative dose of 500 mg fusidic acid. Fusidic acid is a steroid-like antibiotic with a serum half-life of about 10 hours and excellent activity against gram-positive bacteria, including methicillin resistant staphylococci. The neurosurgical infection rates for craniotomies, posterior fossa surgery and implantation of foreign bodies were 2.4% in the treatment group and 9.1% in the placebo group, respectively. This difference is statistically significant at a 95% confidence level. PMID- 8475818 TI - [Temporal stability of the anelasticoendosthymia index]. AB - The authors have researched the test-retest reliability for the Anelasticoendosthenia Index. Data show good correlations. The agreement for two evaluations (Kw = 0.89) and the success probability in 2nd evaluation respect first one (mu = 0.98) are good. PMID- 8475819 TI - [An electromagnetic problem]. AB - Induced psychotic disorder in infrequent. We report a case in which four members of the same family were affected. The bibliography is reviewed and certain etiological factors implicated in our case are discussed. PMID- 8475820 TI - [The Short-Form impairment index (SFII) in schizophrenic patients]. AB - The SFII (Short-Form Impairment Index, Horton and cols, 1986) was used to assess cognitive impairment in patients with DSM-III-R diagnosis of schizophrenia and its relationship to the positive and negative schizophrenic symptoms was studied. Two samples of DSM-III-R schizophrenic patients were studied. The first sample was composed of 30 consecutively inpatients admitted by recrudescence of their symptoms. The second was composed of 19 patients that were attending to a Day Psychiatric Hospital by recrudescence of their symptoms or by socio-familiar dysfunctions. The SFII included three subtest: the "Trail Making" Form B, and cubes and digit symbol from the WAIS, that were converted to typical scores adjusted to age (Reitan, 1973). The positive and negative schizophrenic symptoms were assessed by the Andreasen scales (SAPS y SANS). No differences in epidemiological variables were found between both samples. Higher cognitive impairment (lower SFII) and higher negative symptoms were significantly correlated in both samples. This result suggests that the SFII could be a good marker of cognitive functioning in schizophrenic patients in postacute samples and also in mixed schizophrenic patients (acute and defectual population). The SFII presented some limitations in our young samples derived from their age corrected values. PMID- 8475821 TI - [Rheumatoid arthritis: various psychosomatic aspects]. AB - The rheumatoid arthritis has been considered as a model for the psychosomatic approach in Medicine. The authors present a research in this perspective, trying to evaluate some psychological variables using appropriated rating scales: the self concept, the coping mechanisms and some symptoms like anxiety and depression. A group of diabetics insulin-dependents was the control group. PMID- 8475822 TI - [Extracellular matrix in the sclera]. PMID- 8475823 TI - [Cytotoxic effects of diclofenac sodium]. AB - The authors studied the cytotoxic effect of diclofenac sodium, a prostaglandin synthetic inhibitor, on Chang's cultured human conjunctival cells. Diclofenac sodium inhibited cell growth dose-dependently. Although cell growth was interrupted 12 hrs later by one minute of exposure to a 0.1% solution of diclofenac sodium, the cells began to grow again 24 hrs later. Twenty-four hours later, a one-minute exposure to a 0.1% solution of diclofenac sodium revealed no cytotoxic effects electron microscopically. The effect on the cell cycle of exposure to 0.1% diclofenac sodium was studied using a flow cytometer. Twelve hours after exposure to diclofenac sodium, DNA histograms showed a broader G1 peak, and increase in mitotic phase cells and dead cells with a low DNA content on the left of the G1 peak. 24 hrs later, the number of dead cells and DNA synthetic phase cells increased and mitotic cells gradually decreased, almost disappearing within 48 hrs. PMID- 8475824 TI - [Passive length-tension curves of extraocular muscles after botulinum toxin injection]. AB - Botulinum A toxin was injected into the superior rectus muscles of albino rabbits. Length-tension curves of detached superior rectus muscles were continuously measured with a length and tension measuring device developed by the author. The device consists of a strain gauge for measuring passive length tension, and a position encoder equipped with an eddy current motor. The passive load of the muscle injected with Botulinum A toxin was significantly less than that of control muscle a week after the injection, however, it was greater than that of control muscle in 2 or 3 weeks after the injection. The compliance of the treated muscle was significantly less than that of control muscle at 3 weeks after the injection. PMID- 8475825 TI - [Induction of prostaglandin E2 by interleukin 1 in human lens epithelial cells]. AB - The authors proposed the hypothesis that pseudophakic inflammation, including the fibrin reaction, may be caused by interleukin (IL)-1, IL-6, other cytokines and/or prostaglandins (PGs), synthesized by residual lens epithelial cells (LEC). In testing our hypothesis, we have already detected IL-1 alpha, IL-6 and PGE2 in the culture media of human LEC obtained by capsulotomy during cataract surgery. In this paper, we studied the time course of PGE2-synthesis and interaction between IL-1 and PGE2. PGE2 concentration was measured by radioimmunoassay in the culture media to which rabbit antihuman IL-1 polyclonal antibody was added after culture for 6 h, 1 day, 1, 2, 3, 4, 5 and 6 weeks. There was no increase of PGE2, whereas in the untreated control culture media significant increase of PGE2 was confirmed. The results show that the antihuman IL-1 polyclonal antibody suppressed PGE2-synthesis. Thus, IL-1 induces PGE2 synthesis in human LEC culture. PMID- 8475826 TI - [Adrenergic influence on the outflow facility and the ciliary muscle of enucleated bovine eyes]. AB - In an effort to understand the aqueous outflow mechanism, the author compared changes in the outflow facility with the response of ciliary muscle, using fresh bovine eyes. Neither epinephrine nor isoproterenol alone increased the outflow facility, regardless of their concentrations. However, theophylline, caffeine, isobutylmethylxanthine (IBMX), and other phosphodiesterase (PDE) inhibitors, increased facility in a dose-dependent manner. Epinephrine alone neither relaxed the tone nor inhibited the nerve-mediated contraction of bovine ciliary muscle. Theophylline and IBMX relaxed the tone and inhibited the nerve-mediated contraction, whereas N-ethylmaleimide, iodoacetamide and iodoacetic acid also inhibited the nerve-mediated contraction, and elevated the tone of the ciliary muscle. All PDE inhibitors tested increased the outflow facility and inhibited the nerve-mediated contractions of the ciliary muscle, however, the effect of such drugs on the ciliary muscle tone varied. These results suggest that PDE inhibition may increase the conventional outflow of aqueous humor. PDE inhibitors has much greater influence on and around the outflow channels, from the viewpoint of change of outflow facility and ciliary muscle contraction. PMID- 8475827 TI - [Participation of non-major histocompatibility complex gene in experimental autoimmune uveitis]. AB - It is known that the susceptibility of experimental autoimmune uveitis (EAU) is controlled by both major histocompatibility antigen complex (MHC) and non-MHC genes. In this report, we studied the role of non-MHC gene in the induction of EAU. LEW, WKAH, (LEW x WKAH) F1 and (LEW x WKAH) F2 rats were examined for their incidence and severity to develop EAU by immunization with bovine S-antigen (S Ag). We found that all LEW rats developed severe EAU within 2 weeks after immunization, but no WKAH rat did. Most F1 rats developed mild inflammation in 3 4 weeks after immunization. A quarter of F2 rats developed EAU within 2 weeks, half of them developed it in 3-6 weeks after immunization, and the others did not. These findings suggest that only one non-MHC gene controls the susceptibility to S-Ag induced EAU in rats. PMID- 8475828 TI - [Analysis of blood flow velocity of ophthalmic artery with color Doppler imaging. 1. Studies on normal human eyes]. AB - Color Doppler imaging was used to analyze the blood flow velocity of the ophthalmic artery (BVA) by measuring the pulse wave of flow velocity in the ophthalmic artery of normal subjects. Maximum systolic BVA (Vmax), minimum end diastolic BVA (Vmin), time-averaged BVA (Vmean), Pourcelot index (RI) and pulsatility index (PI) were determined using color Doppler imaging. The coefficients of reproducibility of Vmax, Vmin, Vmean, RI and PI were 10%, 9%, 15%, 4% and 14%, respectively, when analyzed twice at one-hour intervals. There was no significant difference between the values of the right eye and that of the left eye in each case. The averages of Vmax, Vmin, Vmean, RI and PI of 33 normal eyes were 25.4 +/- 7.6 cm/sec, 6.3 +/- 2.3 cm/sec 16.7 +/- 6.6 cm/sec, 0.75 +/- 0.052, 1.19 +/- 0.25 (mean +/- S.D.), respectively, Vmax, Vmin and Vmean decreased significantly with age (Vmax:linear correlation coefficient r = -0.65, p < 0.001; Vmin: r = -0.61, p < 0.001, r = -0.64, p < 0.001. RI did not change with age. PI increased significantly with age (r = 0.30, p < 0.05). PMID- 8475829 TI - [Effects of intraocular pressure on the optic nerve head in albino rabbits]. AB - The effects of intraocular pressure (IOP) on the blood flow in the laminar portion of the optic nerve head in adult albino rabbits were investigated employing the hydrogen clearance method. The blood flow volume at the normal IOP level of 15 mmHg was 119.0 +/- 25.0 ml/min/100 g (mean +/- S.D.). When the IOP was raised every 30 minutes from 5 mmHg to 15, 25, 35, 45 and 55 mmHg in a stepwise fashion, the mean blood flow volume at 5 mmHg was almost the same as the volume at 15 mmHg, but a significant linear decrease was observed at 35 mmHg or more. The decreased blood flow returned to the initial level when the raised IOP was restored to normal. When the IOP was raised to 55 mmHg, the optic nerve potential (ONP) amplitude decreased and the peak latency became gradually prolonged with time, and finally the ONP became almost impossible to measure after 30 minutes, before remarkable changes were noted on the electroretinogram. However, quick recovery of the ONP was recognized within 5 minutes after returning to a normal IOP level of 15 mmHg. These findings indicate that vascular changes might have an important effect on the optic nerve head function or action potential. PMID- 8475830 TI - [Spectral sensitivities on monochromatic backgrounds]. AB - The spectral sensitivities of cone mechanisms were measured on monochromatic backgrounds and the results were compared with the Stiles II-mechanism. Narrow band interference filters with dominant wavelengths of 430 nm and 700 nm were used for background light. The pattern of the spectral sensitivity curve on a 430 nm background with a retinal illuminance of 530 photopic trolands was similar to that of the Stiles II 5-mechanism (long wavelength-sensitive cones). The pattern of the spectral sensitivity curve on a 700 nm background with a retinal illuminance of 530 photopic trolands showed two peaks. The peak in the short wavelength region coincided with that of the short wavelength-sensitive cones and the peak in the middle and long wavelength regions coincided with the Stiles II 4 mechanism (middle wavelength-sensitive cones). As a result, it was suggested that this method is useful to investigate color information processing in both normal and color-defective observers. PMID- 8475831 TI - [Potential laser hazards to bystanders during photocoagulation]. AB - The authors measured reflected laser beams delivered by slit-lamp photocoagulator and binocular indirect ophthalmoscope laser delivery systems, to evaluate potential hazards to the eyes of bystanders. 514 nm laser beams were used; reflected laser beams were measured by a light power meter (Advantest: TQ8210). Reflected lasers were found to be hazardous at 1 meter from whitish tile when a 0.75 Watt laser beam was delivered by the binocular ophthalmoscope laser system, as in an operating room. At 1 meter from a wall in a photo-coagulating room for out-patients, the reflected laser beam was found to be well below hazardous levels. Reflections at 40 cm from a non-laser-coated Goldmann 3-mirror contact lens were 2.66 mW/cm2, which exceeds the exposure limits, when 0.3 W laser was delivered by the slit-lamp photocoagulator. This decreased 85-90% when the laser was reflected from a laser-coated lens. From the point of view of safety, it is recommended that laser surgeons replace non-laser-coated lenses with laser-coated ones. PMID- 8475832 TI - [Histopathology of corneal plaque in vernal keratoconjunctivitis]. AB - The author reported 2 cases of vernal keratoconjunctivitis with corneal plaque showing a white board-like appearance. Conventional medications were not effective in both cases and during the course of the disease corneal ulcer developed followed by formation of corneal plaque. After the plaque spontaneously peeled off, or were surgically removed, the ulcers of both cases healed. The histological specimens from the 2 cases were examined by light and electron microscopy. The plaques showed lamellae-like structures, and formed alternate accumulation of hyaline-like material and another amorphous material. No cell components, such as corneal epithelial cells, keratocytes, or fibroblasts, were found either on the surface of and within the plaques. The corneal epithelial cells and/or eosinophils, however, were found at the edge of the plaque. These findings may suggest that these corneal plaques were formed by repeated episodes of deposition and that corneal epithelial cells and eosinophils may have been involved. PMID- 8475833 TI - [Perimetric glare test and evaluation of intraocular lenses]. AB - Twelve normal control phakic eyes together with a number of other pseudophakic groups each consisting of 6 eyes were enrolled in this study of spatial and quantitative measurement of glare disabilities in the static visual field (Perimetric Glare Test) using an OCTOPUS 500E automated perimeter with an attached glare source. These groups were a 6 mm no hole lens group, a 6 mm 4 hole lens group, a 5.5 x 6.5 mm 2 hole lens group, a 5.0 x 6.0 mm no hole lens group and a diffractive multifocal group. Glare disabilities in the visual field were minimum in the control group. The 6 mm no hole lens group and the diffractive multifocal group showed no statistical significance compared the control group. Groups with the two types of ovoid lens and the 6 mm 4 hole lens group showed a statistically higher degree and a greater extent of glare disabilities in the static visual field than the control group. Careful selection of appropriate patients to receive implants of small efficient optic IOLs, such as IOLs with positioning holes and ovoid lenses, according to the preoperative pupil size under scotopic or mesopic condition and efficient lens optic size are important in order to reduce hole and edge glare. The diffractive multifocal IOLs group showed a slightly higher degree and a greater extent of glare than the control group and the 6 mm no hole monofocal lens group but the difference was very small and statistically insignificant. Therefore the effects of diffractive microstructure on glare disabilities were considered to be slight and clinically acceptable. PMID- 8475834 TI - [Analysis of the effect of PC-IOL implantation on intraocular pressure control in glaucoma eyes using the life-table method]. AB - Cataract extraction and posterior chamber intraocular lens (PC-IOL) implantation were carried out in 21 primary angle glaucoma (POAG) and 26 primary angle closure glaucoma (PACG) eyes in which preoperative intraocular pressure (IOP) was well controlled with medication. The postoperative IOP on the first postoperative day was significantly higher than the preoperative level in POAG eyes, while no significant difference was seen in PACG eyes. The postoperative IOP was significantly lower than the preoperative level at 3 and 6 months postoperatively in POAG eyes and at 1-12 months postoperatively in PACG eyes. Medication did not differ significantly pre- and postoperatively. In 64 +/- 11% (SE) of POAG and 63 +/- 15% of PACG the status of IOP control did not worsen at 2 years. Overall, 70% of the eyes the status of IOP control improved postoperatively, and this was maintained for 2 years in 44 +/- 12%. The present result implies that in primary glaucoma, PC-IOL implantation surgery does not need to be combined with glaucoma surgeries when the IOP was satisfactory controlled and the stage of disease was not advanced. PMID- 8475835 TI - [Glaucoma-like disc without increased intraocular pressure or visual field loss and early stage normal-tension glaucoma disc]. AB - The optic disc topography of 11 eyes of 11 glaucoma-like discs without increased intraocular pressure or visual field loss was compared with that of 11 eyes of 11 relative early stage normal-tension glaucomas. There were no statistically significant differences between the two groups in terms of optic disc parameters measured with a Rodenstock Optic Nerve Head Analyzer Plus, except that the inferior quadrant of the neuroretinal rim area of the normal-tension glaucoma discs was significantly smaller than that of the glaucoma-like discs. Also, in the Humphrey automated visual field, only the superior part of the Total Deviation score of normal-tension glaucoma eyes corresponding to the inferior disc changes was significantly lower than that of glaucoma-like discs. When the data of the two groups were pooled, the inferior quadrant of the neuroretinal rim area significantly correlated with the visual field loss in the group of eyes with a rim area smaller than 0.198 mm2. These results seem to suggest that some of the glaucoma-like discs might be early normal-tension glaucoma. PMID- 8475836 TI - [Clinical evaluation of UF-021 ophthalmic solution in glaucoma patients refractory to maximum tolerable therapy]. AB - UF-021 ophthalmic solution, a novel prostaglandin-related therapeutic agent for glaucoma, was additionally applied to the eyes in intractable cases of primary open angle glaucoma (14 cases, 21 eyes) and ocular hypertension (1 case, 2 eyes) in which intraocular pressure (IOP) had not been kept under satisfactory control even with combined drug therapy by conventional, existing anti-glaucoma agents including sympathetic beta-blockers. Decrease of IOP by UF-021 ophthalmic solution (0.12%) in the treated eyes was observed from not less than one month after the initial application by 3 mmHg and more in about 85%, and by 5 mmHg and more in about 76% of the enrolled patients, respectively. The IOP reduction induced by the additional application of UF-021 was sustained for more than 6 months, resulting in successful avoidance of surgical operations in many patients. When UF-021 ophthalmic solution was applied concurrently with various anti-glaucoma agents including carbonic anhydrase inhibitors, it caused no controversial side-effects and yielded therapeutic efficacy for a prolonged period. These findings suggest that UF-021 can yield IOP-reducing activity through a novel pharmacological mechanism different from other existing drugs. In conclusion, UF-021 ophthalmic solution is extremely useful for the treatment of glaucoma. PMID- 8475837 TI - [A five-year follow-up of the effect of postoperative 5-fluorouracil subconjunctival injections on the surgical outcome of trabeculectomy]. AB - The effects of postoperative subconjunctival 5-fluorouracil (5-FU) injections on the surgical outcomes of trabeculectomy were studied after a 5-year follow-up in 263 eyes of glaucoma patients by the life table analysis. The success probability (%) to maintain the postoperative intraocular pressure (IOP) less than 21 mmHg without medication was 58.2 for primary open angle glaucoma (POAG), 54.8 for secondary glaucoma (SG) and 27.8 for refractory glaucoma, that with or without medication was 92.5 for POAG, 87.4 for SG and 57.5 for refractory glaucoma. The success probability (%) to maintain the postoperative IOP less than 16 mmHg without medication was 55.2 for POAG, 49.8 for SG and 24.5 for refractory glaucoma, that with or without medication was 77.9 for POAG, 66.8 for SG and 26.9 for refractory glaucoma. In each type of glaucoma, the difference between the 5 FU treated and the control groups was highly significant (p < 0.01 or less, log rank test). Corneal epithelial defect was noted in 38.8%, but no late complications, for example, perforation or necrosis of sclera, were observed. These results indicate that we can use postoperative subconjunctival 5-FU without risk of serious complications. PMID- 8475838 TI - [The sub-classification of pre-proliferative diabetic retinopathy]. AB - The authors divided 155 eyes (106 cases) affected by pre-proliferative diabetic retinopathy into three sub-groups according to the severity of retinopathy and followed them for one year. The criteria for and numbers of eyes in each group were as follows; 1) mild type with soft exudate and without apparent non-perfused areas on fluorescein angiography (39 eyes). 2) moderate type with soft exudate and demonstrable non-perfused areas (103 eyes). 3) severe type with soft exudates, non-perfused areas and venous beading (13 eyes). The proportion undergoing photocoagulation was 23% in the mild type, 81% in the moderate type and 100% in the severe type. None of the eyes in the mild type underwent photocoagulation unless they advanced to a more severe type. Nine eyes of the mild type which progressed to moderate type during the follow-up period underwent focal photocoagulation. Panretinal photocoagulation was performed in 29% of moderate type eyes and 77% of severe type eyes. The courses of these three sub groups were analyzed after one year of follow up. The proportion developing proliferative retinopathy was 0% in mild type, 17% in moderate type and 46% in severe type. Based on the above results, we conclude that the sub-classification we propose in this paper can be applied in managing patients with pre proliferative diabetic retinopathy. PMID- 8475839 TI - [Proteoglycan abnormality in a nanophthalmos sclera]. AB - We examined a scleral specimen obtained from a nanophthalmos eye with uveal effusion at the surgery, using cuprolinic blue (CB) dye binding and electron microscopy. The nanophthalmic sclera was separated into two areas electron microscopically. One was an area composed of tightly packed collagen fibers, the other with irregularly arranged collagen fibers. In irregular areas, several abnormal findings, such as twisting or fraying, were detected in collagen fibers, which were surrounded by fine fibrous materials. Furthermore, CB-positive materials were fewer in number and less in size and electron density around the collagen fibers and in fine fibrous materials than in the normal eye. Since the nanophthalmic sclera in this study showed some abnormalities both in collagen fibers and in proteoglycans, we suggest that the function and/or interaction of both of these were abnormal, which might be related to the onset of uveal effusion. PMID- 8475840 TI - [Histological observations on the sclera in uveal effusion]. AB - The author performed sclerectomy in six cases of uveal effusion syndrome and examined the excised sclera histologically. From the findings of the sclera during the surgery and histological findings of the excised sclera, uveal effusion syndrome was divided into three groups: 1) nanophthalmos, 2) non nanophthalmos with hypertrophic sclera, 3) non-nanophthalmos with normal thick sclera. In all cases, glycosaminoglycans were found to be deposited around the scleral collagen fibers. In the nanophthalmic eyes (group 1) and non nanophthalmic eyes with the hypertrophic sclera (group 2), much glycosaminoglycans were demonstrated around the collagen bundles and enlarged the collagen bundle spaces. In these groups, sclerectomy procedures were successful and, based on the successful result of the operation, the cause of uveal effusion was considered to be disturbance of outflow of intraocular fluid through the hypertrophic sclera. In non-nanophthalmic eyes with normal thick sclera (group 3), few glycosaminoglycans was demonstrated around the collagen bundles with less abnormality, and sclerectomy procedure was not effective. In this group, the occurrence of uveal effusion was another cause but abnormal sclera. PMID- 8475841 TI - [A case of benign epithelioma of the ciliary body]. AB - A 34-year-old woman showed a partially pigmented, greyish-white mass at a position of 1 o'clock behind the iris of her left eye. The lens equator was compressed and focal opacity had developed. The adjacent ciliary processes and zonules were intact. Photocoagulation was not effective and dense cataract gradually developed, so we performed extracapsular cataract extraction and partial iridocyclectomy. The tumor was nonencapsulated, nodular and myxomatous in appearance, arising from the pars plicata. Histological examinations revealed that the tumor was composed of nonpigmented cells and a small number of pigmented cell clusters. The cells were arranged like cords or gland-like structure with intervening myxomatous, fibrillar, and partially hyalinous interstitium. There was no finding of malignancy. The tumor showed similar microscopic structure and findings of mucous stains of normal ciliary nonpigmented epithelium and internal basement membrane, so a diagnosis of benign epithelioma was made. PMID- 8475842 TI - Mepron for AIDS-related pneumonia. PMID- 8475843 TI - Dispensing biotechnology products. PMID- 8475844 TI - What is UNIX? PMID- 8475845 TI - A practical billing and payment plan for cognitive services. PMID- 8475846 TI - Dealing with stress on the job. AB - Pharmacists are urged to take an important first step toward effective stress management by considering five questions: How do you know if stress is a problem for you? What is causing most of your stress? Is your supervisor aware of the problem? How do you deal with stress? What can you do to reduce the impact of stress? Because uncontrolled job stress has been associated with serious negative consequences, pharmacists owe it to themselves to explore strategies that they can use to manage stress in their lives. PMID- 8475847 TI - Can a community pharmacist add value to prescriptions? PMID- 8475848 TI - Consumers' evaluation of value-added pharmacy services. AB - One proposal for community pharmacies to survive in an increasingly competitive market is to offer services that consumers want and need. This study examined the effects of such a value-added pharmacy services (VAPS) program implemented at 19 experimental pharmacies; another 16 pharmacies served as a control group. The study found that patrons of VAPS pharmacies received more pharmacy services and were more likely to report that the pharmacist talked to them about their medication than patrons of control pharmacies. This study demonstrates that a value-added services program can have an impact on pharmaceutical services. PMID- 8475849 TI - OBRA '90: turning a challenge into an opportunity. PMID- 8475850 TI - Antiacne products--no benzoyl peroxide. PMID- 8475851 TI - On-line continuing education. PMID- 8475852 TI - Getting information about biotechnology products. PMID- 8475853 TI - New drugs of 1992. PMID- 8475854 TI - FDA OTC advisory group needs practitioners. PMID- 8475855 TI - How to communicate with physicians. PMID- 8475856 TI - Improving your patient counseling skills. AB - This article has offered several suggestions to help begin the process of improving patient counseling skills. Recommendations for changing how to think about patient communication and for developing new communication skills were discussed. It would be comforting if the idea of improved patient counseling could be packaged in an easy-to-learn, three-step program. It would be convenient if learning patient counseling skills could be achieved by simply attending a lecture or reading an article. Programs and articles are good starting points, but improving patient counseling skills requires a good deal of motivation, knowledge, and practice. My sense from the feedback I have received, after working with pharmacy students and practitioners for almost 15 years, is that those prepared to commit themselves to a program of improvement have benefited personally and professionally. How quickly they developed their skills has varied, and the degree of effectiveness among them may be somewhat different; however, the ultimate issue is that they all were able to improve. PMID- 8475857 TI - Ethical decision making in pharmacy practice. PMID- 8475858 TI - PMA survey cites advances in AIDS research. PMID- 8475859 TI - Legislation needed for chains to change. PMID- 8475860 TI - Dose-related efficacy and bleeding complications of double-chain tissue plasminogen activator in acute myocardial infarction. The Wellcome Tissue Plasminogen Activator Study Group. AB - Although the efficacy of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double chain rt-PA subsequently used in the Third International Study of Infarct Survival, in a multicenter trial of 267 patients with evolving acute myocardial infarction assigned to receive 1 of 6 weight-adjusted doses. The primary end point was infarct vessel patency after 90 minutes of drug infusion. Patency was defined as Thrombolysis in Myocardial Infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatment assignment. Patency was present in 48% of patients receiving the lowest dose range and 78% of those receiving the highest, with an association between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt-PA infused (p = 0.003). Bleeding complications were primarily related to instrumentation; blood loss requiring transfusion or otherwise deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt-PA are associated both with increased efficacy and increased risk of serious bleeding complications. Weight-adjusted dosing may provide an optimal risk-benefit ratio for thrombolysis during acute myocardial infarction. PMID- 8475861 TI - Influence of reperfusion induced by thrombolytic treatment on natural history of left ventricular regional wall motion abnormality in acute myocardial infarction. AB - Although several studies have investigated left ventricular (LV) function after reperfusion interventions, it is still unclear whether benefits result from successful therapy or whether such benefits only reflect the natural history of a subgroup of patients with acute myocardial infarction (AMI). This study evaluates the unique effect of thrombolytic therapy on the natural history of regional LV wall motion dysfunction. One hundred seventy-six patients with AMI were studied: 82 patients (group A) underwent conventional treatment and 94 (group B) thrombolytic therapy. LV regional improvement, evaluated by changes in echo score between admission and predischarge examination, was present more frequently in group B (28%) than in group A (17%). Furthermore, improved patients in group B had higher admission echo scores (7.5 +/- 3.5 vs 6.3 +/- 3.1), a prevalence of anterior AMI (68 vs 30.1%) and a higher rate of coronary patency (92 vs 58% in patients who had no improvement). In group A patients the rate of coronary patency was similar in those who did (46.1%) and did not have (36.1%) improvement. Observations at 12 to 18 months showed similar data in group A patients and in group B patients without improvement, whereas a marginal additional improvement was observed in group B patients who had in-hospital improvement. These observations demonstrate that LV function recovery is more frequent and marked in treated than in untreated patients. Follow-up results suggest a prolonged beneficial effect of thrombolytic treatment on LV function. The highest rate of coronary patency in improved group B patients underline the role of reperfusion on natural history of LV dysfunction after AMI. PMID- 8475862 TI - Occurrence of hypotension during streptokinase infusion in suspected acute myocardial infarction, and its relation to prognosis and metoprolol therapy. AB - In all patients who received streptokinase infusion for strongly suspected acute myocardial infarction in 1 hospital during 1989 to 1990, the occurrence of hypotension during infusion is described and related to prognosis. In 54% of patients, the beta blocker metoprolol was simultaneously administered intravenously. The median systolic blood pressure (BP) before infusion was 135 mm Hg, and the median value for the lowest systolic BP recorded during infusion was 100 mm Hg (p < 0.001). A positive correlation between systolic BP before streptokinase and the lowest systolic BP during infusion was found (r = 0.53; p < 0.001). Among patients administered streptokinase and metoprolol, 23% had systolic BP < 90 mm Hg, and 12% had < 80 mm Hg at any time during infusion; corresponding values for patients administered streptokinase only were 47 and 30%, respectively. Patients with the lowest systolic BP < 80 mm Hg during infusion had a mortality during the first 2 weeks of 22 vs 11% for those with between 80 and 100 mm Hg, and 8% for those with > 100 mm Hg (p < 0.001). However, in a multivariate analysis the systolic BP before infusion rather than the lowest systolic BP during infusion was independently associated with death. It is concluded that although patients with low systolic BP during streptokinase infusion have a high mortality, the level of systolic BP before infusion is more strongly associated with the outcome. Simultaneous use of intravenous beta blockade does not increase the occurrence of hypotension during streptokinase infusion. PMID- 8475863 TI - Mechanism and significance of precordial ST-segment depression during inferior wall acute myocardial infarction associated with severe narrowing of the dominant right coronary artery. AB - The mechanism and significance of precordial ST depression during inferior wall acute myocardial infarction (AMI) is debated. This study assessed the location and extent of arterial perfusion distribution responsible for this electrocardiographic finding. Intracoronary thallium-201 was injected in 11 patients with 1-vessel right coronary disease to delineate perfusion distribution that was quantitated by a new angiographic distribution score. The angiographic score correlated with posterior (r = 0.84), posterolateral (r = 0.88) and total (r = 0.73) extent of intracoronary thallium distribution. The angiographic distribution score was related to electrocardiographic changes in 16 patients showing an inferior ST-segment elevation during angioplasty (7 with and 9 without precordial ST depression), of which 6 received intracoronary thallium injection. None had thallium distribution in the anterior or septal segment, but there was a trend toward a greater angiographic distribution score and posterior segment thallium score in patients with precordial ST depression. In another 77 patients with inferior wall AMI due to right coronary occlusion (24 with concomitant left anterior descending narrowing), precordial ST depression was present in 16 with and 31 without left anterior descending narrowing (p = NS). The angiographic distribution score was higher in those with than without precordial ST depression (0.59 +/- 0.10 vs 0.44 +/- 0.11, p < 0.001) in both patients with and without left anterior descending disease. The magnitude of both inferior ST elevation and precordial ST depression correlated with the angiographic distribution score, but only precordial ST depression was independently related in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475864 TI - Comparison of long-term outcome after acute myocardial infarction in patients never graduated from high school with that in more educated patients. Multicenter Investigation of the Limitation of Infarct Size (MILIS). AB - The clinical course of 363 patients with acute myocardial infarction who did not complete high school education was compared with that of 453 who completed at least high school. Both the in-hospital and 4-year mortality rates were markedly greater for the less educated than for the more educated patients (13 vs 5% [p < 0.001], and 36 vs 17% [p < 0.001]). Adverse baseline characteristics were partially responsible for the increased in-hospital (p = 0.059 after adjustment) and long-term (p = 0.024 after adjustment) mortality. The less educated patients were not as likely to quit smoking after acute myocardial infarction as were the more educated ones (38 vs 49%; p < 0.05). Patients who continued smoking had a greater mortality than did those who quit (24 vs 15% [p < 0.05] for less educated, and 10 vs 4% [p < 0.05] for better educated). Therefore, greater effort should be directed to smoking cessation among the high-risk group of less educated patients. However, the smoking continuation was responsible for only a small portion of the mortality difference, suggesting unidentified causes of mortality, such as lack of compliance with therapy and possible social isolation. Despite the high-risk status of the less educated patients, cardiac catheterization tended not to be performed as frequently as in the more educated patients after discharge from the hospital (16 vs 21%; p < 0.06 at 6 months). PMID- 8475865 TI - Comparison of magnetic resonance imaging studies with enzymatic indexes of myocardial necrosis for quantification of myocardial infarct size. AB - To evaluate the potential of gadolinium-diethylene triamine pentaacetic acid (DTPA)-enhanced magnetic resonance imaging (MRI) in the quantification of infarct size in patients with a first acute myocardial infarction, 24 patients with a first acute myocardial infarction were studied by electrocardiographic gated MRI at a mean of 4.3 days after the acute event. Multislice, single-phase, T1 weighted, spin-echo MRI in the true short-axis plane was performed 20 minutes after intravenous injection of gadolinium-DTPA (0.15 mmol/kg of body weight). Circumscript myocardial regions of increased signal intensity on gadolinium-DTPA enhanced images were considered to be infarcted. Infarct size (in g) was determined using Simpson's rule, and was compared with that based on cumulative release of alpha-hydroxybutyrate dehydrogenase activity in plasma and with peak creatine kinase-MB level in plasma. Infarct size quantified with MRI correlated well with "enzymatic" infarct size (in g equivalents) (y = 0.99 x + 0.71; r = 0.93; p = 0.0001) and peak creatine kinase-MB levels (r = 0.72; p = 0.002). It is concluded that gadolinium-DTPA-enhanced MRI enables accurate quantification of infarct size in patients with a first acute myocardial infarction. PMID- 8475866 TI - Effect of enhanced preload with head-out water immersion on exercise response in men with healed myocardial infarction. AB - Head-out water immersion shifts venous blood to the central vasculature and heart and subsequently increases cardiac preload. In healthy men, cardiac output and stroke volume are greater during upright leg cycle exercise in water than on land. Heart rate is similar during work loads < 50% of peak oxygen consumption but is decreased in water at higher work intensities. To determine if men with myocardial infarction (MI) show a similar response, 15 men with a documented MI exercised upright on a leg cycle ergometer on land and immersed in water (31 +/- 1 degree C) to the level of the shoulders. Heart rate, cardiac output (carbon dioxide rebreathing procedure) and oxygen consumption were measured at rest and at work loads corresponding to approximately 40, 60 and 75% of peak oxygen consumption in both environments. At rest, cardiac output and stroke volume were elevated (p < 0.05) in water. During exercise, heart rate, cardiac output and stroke volume did not differ between water and land. When subjects were given beta-blocking medications (n = 8) and subjects with exercise-induced ST-segment depression (n = 5) were separately excluded from the analysis, water immersion still did not significantly change exercise responses. These results suggest that MI alters the normal cardiac response to increased preload during exercise. The alteration may involve reduced myocardial compliance or near-complete use of the Frank-Starling reserve, or both, during land exercise. PMID- 8475867 TI - Does the myocardium become "stunned" after episodes of angina at rest, angina on effort, and coronary angioplasty? AB - To assess whether myocardial stunning occurs after brief periods of ischemia, global and regional ventricular function assessed by radionuclide angiography was studied in 52 patients. Patients were divided into 3 groups according to the type of ischemic episodes. Group 1 consisted of 15 patients studied before, during and after episodes of angina at rest. Seventeen patients studied immediately before and after coronary angioplasty constituted group 2. Group 3 consisted of 20 patients with stable angina studied before, during and after exercise-induced ischemia. Medical therapy was discontinued 48 hours before the study in all patients except those undergoing coronary angioplasty who were receiving diltiazem 180 mg/day. No difference in baseline ejection fraction was found between groups, whereas peak filling rate was statistically lower in group 3 patients. Evidence of left ventricular dysfunction during ischemia was seen in patients in groups 1 and 3, whereas transient ischemia was documented by ST segment displacement and/or typical chest pain during balloon inflation in group 2. Persistence of systolic or diastolic dysfunction was not observed in any of the 3 groups in the recovery phase after ischemia. In conclusion, transient ischemia caused either by a primary reduction in oxygen supply (angina at rest, coronary angioplasty) or by an increase in oxygen demand (angina on effort) did not reproduce the phenomenon of systolic and diastolic stunning observed in animal experiments, although in all patients the ischemia was of sufficient duration and severity to induce marked ventricular dysfunction. The search for stunned myocardium should be extended to other different clinical models characterized by prolonged ischemia such as unstable angina or myocardial infarction. PMID- 8475868 TI - Exercise thallium scintigraphy versus high-dose dipyridamole echocardiography testing for detection of asymptomatic restenosis in patients with positive exercise tests after coronary angioplasty. AB - The usefulness of high-dose (< or = 0.84 mg/kg over 10 minutes) dipyridamole echocardiography testing was compared with that of exercise thallium-201 scintigraphy in detecting restenosis (> 70% lumen reduction) in 50 asymptomatic patients with ST-segment depression during maximal exercise testing 3 months after successful coronary angioplasty. Dipyridamole echocardiography testing and exercise thallium scintigraphy showed a similar sensitivity (75 vs 83%; p = NS) and specificity (90 vs 84%; p = NS) for the detection of restenoses, which occurred in 12 patients. It is concluded that dipyridamole echocardiography testing is as accurate as exercise thallium testing for the noninvasive detection of severe restenosis in patients with exercise-induced asymptomatic ST-segment depression after successful angioplasty. Furthermore, the site, extent and severity of the thallium perfusion defects during exercise are correlated to those of the dyssynergy during dipyridamole echocardiography. PMID- 8475869 TI - Once-daily, extended-release gemfibrozil in patients with dyslipidemia. The Lopid SR Work Group I. AB - This randomized, parallel-group, multicenter clinical trial compared a newly developed, once-daily, extended-release formulation of gemfibrozil (Lopid SR) and gemfibrozil twice daily (Lopid) in terms of lipid-regulating effects and toxicity. Patients were men and women with elevations of low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol. The trial consisted of a 1-week screening period, an 8-week diet baseline period (Step One Diet), and a 24-week double-blind treatment period (extended-release gemfibrozil 1,200 mg once daily vs gemfibrozil 600 mg twice daily). At the end of the trial, the 2 treatment groups showed comparable improvements in all primary lipid factors: mean percent changes in triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were -32, +10 and -10% for extended release (n = 325) and -36, +11 and -10% for twice daily (n = 330). The 90% confidence interval for the relative difference between the treatment means fell within the equivalence bounds of +/- 35% for all 3 factors, demonstrating equivalence of efficacy. Adverse events were reported at low rates and were similarly distributed in frequency and intensity between treatment groups; they were preponderantly mild or moderate, and gastrointestinal effects were the most frequent. The once-daily formulation of gemfibrozil may afford better control of dyslipidemia through improved compliance by patients who have this asymptomatic disease. PMID- 8475870 TI - Comparison of frequency of aggravation of ventricular tachyarrhythmias after implantation of automatic defibrillators using epicardial versus nonthoracotomy lead systems. AB - The time of onset of 4,471 episodes of ventricular tachycardia (VT) or fibrillation (VF) in 40 of 65 patients with an implantable cardioverter defibrillator (ICD) with endocardial defibrillation electrodes (group 1) and in 53 of 123 with epicardial defibrillation electrodes (group 2) was analyzed to examine whether the incidence of VT/VF immediately after surgery is greater than during further follow up and whether the site of lead placement exerts an influence on the occurrence of these arrhythmias. Actuarial survival rates free of VT/VF were 77, 65, and 54% at 1, 3 and 6 months, respectively, for group 1, and 84, 66 and 52%, respectively, for group 2. The probability of VT/VF was increased only during the first week after surgery; in that week, 12.8% of all patients had VT/VF, without significant differences between groups 1 and 2. Until the end of the first month, this percentage increased to 23%, whereas only 12 to 15% of patients had VT/VF during subsequent months. In 19 patients with third generation devices capable of terminating tachycardias by overdrive pacing, 326 of 412 VT/VF episodes occurring in the first week after surgery were terminated by antitachycardia pacing, and only 86 had to be terminated by cardioversion or defibrillation. No postoperative exacerbation of inappropriate ICD therapies was observed in any group; 2 to 5% of patients per month received ICD therapies for atrial fibrillation or sinus tachycardia. Patients who received appropriate ICD therapies in the first week after surgery were at high risk of recurrence of VT/VF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475871 TI - Assessment of quality of life as observed from the baseline data of the Studies of Left Ventricular Dysfunction (SOLVD) trial quality-of-life substudy. AB - The improvement of aspects of a patient's quality of life may be as important as prolonging survival in evaluating clinical trials of heart failure. The purpose of this study was to analyze the psychometric properties of the baseline measures from the quality-of-life substudy from the Studies of Left Ventricular Dysfunction (SOLVD) trial. The measures included the 6-Minute Walk Test, Dyspnea Scale, Living with Heart Failure, Physical Limitations, Psychologic Distress and Health Perceptions, as reported by both patients and staff. Cognitive functioning, such as Vocabulary, Digit Span and Trails Making, was also assessed. Patients were classified as New York Heart Association class I (n = 158) versus II or III (n = 150). The internal consistencies (i.e., reliabilities) of the self report measures were high, except for the Health Perceptions of Class II or III patients. Reliability of the SOLVD quality-of-life battery was confirmed by significantly better life quality among New York Heart Association class I patients versus class II or III patients combined on the Walk Test, Physical Limitations, Dyspnea, Living with Heart Failure, Psychologic Distress and staff perceptions of patient health. In accordance with prior studies, the measures were uncorrelated with left ventricular ejection fraction. By demonstrating strong internal consistencies, reliability based on physician reports, and independence of ejection fraction levels, use of this quality-of-life assessment battery in this and other clinical trials of compromised ventricular functioning is supported. PMID- 8475872 TI - Rapid assessment of aortic regurgitation and left ventricular function using cine nuclear magnetic resonance imaging and the proximal convergence zone. AB - In patients with aortic regurgitation (AR), knowledge of the severity of AR, and the degree of left ventricular (LV) dysfunction are important for optimal management. Previous nuclear magnetic resonance (NMR) studies to assess these parameters used multiple tomographic planes that are time-consuming to obtain and analyze, and thus not cost-effective. In addition, these studies assessed the severity of AR by looking simply at the size of the regurgitant jet, a parameter that relates only poorly to regurgitant volume. The present study evaluates a rapid, single-plane, cine NMR approach (scan time < 10 minutes), and a new grading system for AR that is based on the presence, size and persistence of not only the regurgitant jet, but also the zone of proximal signal loss. Compared with color Doppler echocardiography (n = 42), the NMR approach detected AR with a specificity of 100% and a sensitivity of 95%. NMR regurgitant jet area correlated well with color Doppler regurgitant jet area (n = 20; r = 0.81; p < 0.01), but did not discriminate well between all grades of AR as compared with x-ray contrast aortography (n = 14). Using the new NMR grading criteria, AR grade by NMR was in accordance with aortographic grade in 12 patients, differing by only 1 grade in the remaining 2 patients. NMR grade was in accordance within 1 grade of Doppler in all patients compared (n = 20). LV volumes and ejection fraction using this single-plane approach correlated well with a previously validated, NMR biplane approach (r > 0.87; n = 18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8475873 TI - Comparison of active infective endocarditis involving a previously stenotic versus a previously nonstenotic aortic valve. AB - No previous studies, either clinical or morphologic, have compared findings in patients with active infective endocarditis (IE) involving a previously stenotic versus a previously nonstenotic aortic valve. Clinical and cardiac necropsy findings were analyzed in 96 patients with active IE involving the aortic valve. Of the 96 patients, 25 (26%) had active IE superimposed on a previously stenotic aortic valve and 71 (74%) on a previously nonstenotic aortic valve. The patients with stenotic aortic valves compared with those with nonstenotic aortic valves had significantly higher mean ages (61 vs 47 years), a higher percentage > 60 years of age (52 vs 24%), a higher percentage of men (92 vs 73%), a higher frequency of an absent or unknown predisposing factor to infection (68 vs 38%), a lower frequency of a precordial murmur of aortic regurgitation (44 vs 79%), a lower percent with a long duration (> 60 days) of signs and symptoms of active IE (4 vs 23%), a larger mean heart weight (594 vs 514 g), a higher percentage with aortic valve calcific deposits (100 vs 24%), and a higher frequency of associated ring abscess (84 vs 52%). Thus, active IE superimposed on a stenotic aortic valve differs in some features compared with active IE on a nonstenotic aortic valve. Because ring abscess is so common when active IE involves a stenotic aortic valve in adults, operative intervention at an early stage may be warranted. PMID- 8475874 TI - Morphologic basis for obstruction to right ventricular outflow in hypertrophic cardiomyopathy. AB - The mechanism by which obstruction to right ventricular (RV) outflow occurs in patients with hypertrophic cardiomyopathy (HC) is not well understood. To clarify this issue, 5 severely symptomatic patients (aged 18 to 55 years, mean 30) with HC and marked subpulmonic obstruction (basal peak systolic pressure gradients 60 to 118 mm Hg) were studied. Four patients also had obstruction to left ventricular outflow (maximal basal or provocable pressure gradient 12 to 110 mm Hg). The RV outflow obstruction in each patient resulted from greatly hypertrophied musculature comprised of crista supraventricularis, moderator band or trabeculae. Operative resection of portions of this muscle resulted in abolition or substantial reduction of the RV outflow gradient (to 0 to 11 mm Hg) in the 3 patients with both pre- and postoperative hemodynamic studies. The left ventricular wall and ventricular septum also were massively thickened (32 to 40 mm) in each patient. These findings support the view that marked RV outflow tract obstruction in patients with HC is due to greatly hypertrophied RV muscle, and that operative resection will relieve the outflow gradients and normalize RV systolic pressure. The muscular RV hypertrophy causing obstruction appeared to constitute a primary and excessive hypertrophic process involving both ventricles. PMID- 8475875 TI - Left ventricular wall tension and stress during exercise in athletes and sedentary men. AB - This investigation examines the hypothesis that hypertrophy attenuates wall stress during exercise, when left ventricular wall tension is highest and most likely to contribute to hypertrophy. Upright bicycle exercise was performed by 17 endurance-trained male athletes and 15 sedentary men. M-mode echocardiograms were obtained during submaximal exercise at predetermined heart rates. At all levels of exercise, at a matched heart rate, wall tension was higher in athletes than in sedentary subjects. In both groups, wall tension increased with exercise, then plateaued. Wall stress did not differ significantly in athletes and sedentary subjects at rest and at heart rates of 110 and 150 beats/min, although a difference was observed at a heart rate of 130 beats/min. Wall stress decreased in both athletes and sedentary subjects with exercise. In conclusion, left ventricular hypertrophy caused wall stress in athletes to be maintained at values similar to sedentary subjects during exercise as well as at rest. PMID- 8475876 TI - Usefulness of the impedance cardiogram to reflect left ventricular diastolic function. AB - The impedance diastolic waveforms, early O wave (zO) and late A wave (zA), were evaluated, and their relation to diastolic mitral flow patterns under changes in loading conditions was assessed. Eight normal subjects and 9 patients with Doppler evidence of delayed ventricular relaxation were studied with simultaneous transmitral Doppler flow and computerized, ensemble-averaged, impedance cardiography in the supine position. Thirty-degree, head-down and head-up tilt were performed to alter preload. Peak Doppler early diastolic velocity (E) and E integral were preload-dependent in both normal and abnormal groups (p < 0.003), but were not significantly different between patients and normal subjects. Peak Doppler late diastolic velocity (A) and A integral, although significantly different between groups (p < 0.001), did not vary significantly with tilt. E/A ratio was significantly different between groups in all positions (p < 0.006). Impedance zA was preload-dependent (p < 0.001) in both groups and significantly different between groups (p < 0.05). Impedance zO was also preload-dependent (p < 0.003), but not significantly different between groups. Impedance zO correlated with Doppler peak E (r = 0.64; p = 0.001). Impedance zA did not correlate with Doppler A. Impedance cardiography diastolic waveforms can be altered by position and may reflect changes in vena caval or pulmonary vein volume flow, or both. This technique, in combination with Doppler mitral flow patterns, may be useful in evaluating diastolic function. PMID- 8475877 TI - Effect of operator experience on outcome of radiofrequency catheter ablation of accessory pathways. PMID- 8475878 TI - Validity of the Minnesota Living with Heart Failure questionnaire as a measure of therapeutic response to enalapril or placebo. PMID- 8475879 TI - Coronary arterial patterns in double-outlet right ventricle. PMID- 8475880 TI - Ejection characteristics in primary pulmonary hypertension. PMID- 8475881 TI - Role of transesophageal echocardiography in diagnosis and management of central pulmonary artery thromboembolism. PMID- 8475882 TI - Effects of bilateral hystero-salpingo-oophorectomy on exercise-induced ST-segment abnormalities in young women. PMID- 8475883 TI - Validation study of a Doppler-tipped angiographic catheter for measurement of a coronary flow reserve. PMID- 8475884 TI - Thrombolytic therapy for acute myocardial infarction in a 110-year-old man. PMID- 8475885 TI - Temporary DDD pacing after surgically induced heart block. PMID- 8475886 TI - Successful management of labor and delivery in primary pulmonary hypertension. PMID- 8475887 TI - ISIS-3 and GISSI-2: no survival advantage with tissue plasminogen activator over streptokinase, but a significant excess of strokes with tissue plasminogen activator in both trials. PMID- 8475888 TI - Effects of the individual saturated fatty acids on serum lipids and lipoprotein concentrations. AB - A mixture of dietary saturated fatty acids raises the serum total cholesterol concentrations compared with a diet of isoenergetic amounts of carbohydrates. Saturated fatty acids are not all equally hypercholesterolemic: stearic acid (18:0) and saturated fatty acids with < 12 carbon atoms are thought not to raise serum cholesterol concentrations. This suggest that the cholesterol-raising properties of saturated fatty acids should be attributed solely to lauric acid (12:0), myristic acid (14:0), and palmitic acid (16:0). These three saturated fatty acids, however, may have different effects on serum total-cholesterol concentrations as well. Results from controlled dietary experiments suggest that lauric acid (12:0) is less, and myristic acid (14:0) probably more, hypercholesterolemic than palmitic acid (16:0). Effects of the different saturated fatty acids on the distribution of cholesterol over the various lipoproteins are largely unknown, but it is suggested that stearic acid lowers HDL cholesterol concentrations relative to other saturated fatty acids. At present, however, too many questions are unanswered to quantitate these differences. PMID- 8475889 TI - Lipid peroxidation: its mechanism, measurement, and significance. AB - An increased concentration of end products of lipid peroxidation is the evidence most frequently quoted for the involvement of free radicals in human disease. However, it is likely that increased oxidative damage occurs in most, if not all, human diseases and plays a significant pathological role in only some of them. For example, peroxidation appears to be important in atherosclerosis and in worsening the initial tissue injury caused by ischemic or traumatic brain damage. Oxidative stress can damage many biological molecules; indeed, proteins and DNA are often more significant targets of injury than are lipids, and lipid peroxidation often occurs late in the injury process. Many assays are available to measure lipid peroxidation, but no single assay is an accurate measure of the whole process. Application of simple diene-conjugate and thiobarbituric acid (TBA) assays to human tissues and body fluids can produce artifacts. An HPLC based TBA test can eliminate some of these artifacts. PMID- 8475890 TI - Apolipoprotein metabolism: a stable-isotope approach. AB - Lipids are the major fuel of the body. Efficient functioning as an energy source dictates that lipids must be transportable in the plasma from the point of synthesis and assembly to the storage depots and finally to the tissues to provide energy through oxidative metabolism. Complex lipid forms are transported through the plasma as lipoprotein particles. These particles, secreted from the intestine and liver, have nonpolar outer surface composed of cholesterol, phospholipids, and apolipoproteins. Apolipoproteins are essential for the production, secretion, and continued structural integrity of the various lipoprotein particles and thus play a pivotal role in the control mechanisms of lipid transport. Apolipoproteins regulate specific enzyme activities and modulate plasma lipoprotein clearance through receptor-mediated processes. Quantitative information regarding the rates of synthesis and catabolism of apolipoproteins is vital to an understanding of their metabolism in health and disease. General considerations are followed by a specific use of stable-isotope methodology to quantitative the rate of synthesis of very-low-density-lipoprotein apolipoprotein B-100 (VLDL apo B-100) in control and familial-combined-hyperlipidemic (FCHL) patients. PMID- 8475891 TI - The regulatory, informational, and immunomodulatory roles of fat fuels. AB - Fat oxidation provides a fuel for many tissues and it provides an important signal to decrease glucose utilization and oxidation in muscle and so conserve glucose for essential organs such as the brain. The control of fatty acid oxidation is achieved in part through its plasma concentrations, which may be precisely controlled by the triacylglycerol-fatty acid substrate cycle, which can also, if oxidation is taken into account, be viewed as a branch point in this important pathway. Branch points may provide precision in regulation if one of the fluxes at the branch is low compared with the other flux. Both branch points and substrate cycles are energetically expensive and may account for some of the increases in energy expenditure in conditions of injury, burns, and sepsis and in the postexercise condition. Fatty acids, through effects on plasma free tryptophan concentrations and hence 5-hydroxytryptamine concentrations in the brain, may play a role in central fatigue. Polyunsaturated fatty acids are claimed to have immunosuppressive properties. Work has been done to provide a biochemical analysis of how they might influence some functions of cells of the immune system. PMID- 8475892 TI - Free fatty acids and exercise. AB - Although the great explorers were well aware that eating fat was an efficient way to meet their large energy demand, it was not until some decades into this century that it could be demonstrated that lipids are metabolized directly by contracting skeletal muscles. The 1950s produced the first studies with [14C] tagged fatty acids (FAs), proving that fat is transported into the cell as FAs. An FA-transporting protein that is present in the sarcolemma and in the cytoplasma has been identified. For FA transport into the mitochondria, carnitine and carnitine transferase are needed. It is still unclear how the use of lipids as an energy source for the muscle during exercise is limited. The supply of free fatty acids (FFAs) far exceeds what is taken up by the muscle. Seldom more than 2 4% of the amount of FFAs delivered to an exercising limb is taken up by the muscles and only part of it is oxidized. Physical training induces changes that enhance the uptake of FAs by the contracting muscles, and a larger fraction of this uptake is oxidized, but it is not yet clear which mechanism is behind this adaptation. What is known is that this uptake occurs despite no elevation in the amount of FA supplied to the limb. PMID- 8475893 TI - Food quotient, respiratory quotient, and energy balance. AB - This paper reviews evidence that the macro-nutrient composition of the diet and the maintenance of energy balance are correlated. Intervention studies show that subjects lose weight on low-fat diets and gain weight on high-fat diets. Descriptive studies show that overweight subjects eat relatively more fat but have the same total energy intake as nonoverweight subjects. The body has a limited ability to oxidize fat compared with its ability to oxidize carbohydrate and protein. The conclusion is that becoming overweight can be prevented by reducing the fat content of the diet. Studies on nutrient utilization show a ready increase in carbohydrate oxidation whereas fat oxidation does not change after meals enriched with, respectively, carbohydrate or fat. However, in the long term, the respiratory quotient (RQ) is closer to the food quotient (FQ) for subjects eating high-fat diets than it is for subjects eating high-carbohydrate diets. For high-carbohydrate diets, the RQ is lower than is the FQ, indicating that subjects must mobilize body fat. This is supported by data on body weight loss in subjects changing from a standard maintenance diet to a low-fat diet, even while energy intake was increased with nearly 20%. Direct evidence for a higher energy expenditure for low-fat diets is not yet available. PMID- 8475894 TI - Energy balance or fat balance? AB - Under normal conditions, carbohydrate, protein, and alcohol are not converted to fat. Glycogen and protein stores are closely controlled, and increasing the intake of nonfat nutrients stimulates their oxidation rates proportionally. Thus, chronic imbalance between intake and oxidation of nonfat nutrients cannot lead to obesity. On the other hand, fat stores are not controlled and their capacity for expansion is enormous. Because an increase in fat intake does not stimulate fat oxidation, a positive fat balance results, which has the potential to become chronic. Obesity is therefore due to a long-standing positive fat balance, which may simply be due to a high-fat diet. The use of the fat-balance equation instead of the energy-balance equation adds another option for the treatment of obesity- that of changing the quality of the diet, ie, lowering the fat content. PMID- 8475895 TI - Dietary fat and the control of energy intake: evaluating the effects of fat on meal size and postmeal satiety. AB - Three separate experiments in lean subjects confirmed that a 1.52-MJ (362-kcal) carbohydrate supplement at breakfast suppressed appetite 90 min later but had no effect on a test meal given after 270 min. A 1.52-MJ (362-kcal) fat supplement produced no detectable action on measures of appetite at any time point. Therefore, fat and carbohydrate do not have identical effects on the appetite profile. In a further study in obese subjects, a novel experimental design was used to assess the satiating efficiency and compensatory response of fat. Eating from a range of either high-fat or high-carbohydrate foods, obese subjects voluntarily consumed twice as much energy from the fat items, thereby indicating a weak action of fat on satiation. In turn, this large intake of fat exerted a disproportionately weak effect on satiety. These studies suggest that the appetite-control system may have only weak inhibitory mechanisms to prevent the passive overconsumption of dietary fat. The results indicate how this action could induce a positive energy balance and lead to a gradual upward drift in body mass index. PMID- 8475896 TI - Cytotoxicity and genotoxicity of lipid-oxidation products. AB - The autoxidation of unsaturated lipids contained in oils, fats, and food and the endogenous oxidative degradation of membrane lipids by lipid peroxidation result in the formation of a very complex mixture of lipid hydroperoxides, chain cleavage products, and polymeric material. Experimental animal studies and biochemical investigations lend support to the hypothesis that lipid-oxidation products, ingested with food or produced endogenously, represent a health risk. The oral toxicity of oxidized lipids is unexpectedly low. Chronic uptake of large amounts of such materials increases tumor frequency and incidence of atherosclerosis in animals. 4-Hydroxynonenal, a chain-cleavage product resulting from omega 6 fatty acids, disturbs gap-junction communications in cultured endothelial cells and induces several genotoxic effects in hepatocytes and lymphocytes. Although the concentrations of the aldehyde needed to produce these effects are in the range expected to occur in vivo, their pathological significance is far from clear. Recent findings strongly suggest that in vivo modification of low-density lipoprotein by certain lipid-peroxidation products (eg, 4-hydroxynonenal and malonaldehyde) renders this lipoprotein more atherogenic and causes foam-cell formation. Proteins modified by 4-hydroxynonenal and malonaldehyde were detected by immunological techniques in atherosclerotic lesions. PMID- 8475897 TI - Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. AB - For the prolongation of life expectancy and reduction of ischemic heart disease (IHD) dietary guidelines generally recommend lowering saturated mammalian fat with partial replacement by vegetable oils and increasing generously vegetables, legumes, and fruits, which provide more essential antioxidants. Plasma antioxidants as assayed in epidemiological studies of complementary type (ie the cross-cultural MONICA Vitamin Substudy reevaluation considering the "Finland Factor", the Edinburgh Angina-Control Study, and the Basel Prospective Study) consistently revealed an increased risk of IHD (and stroke) at low plasma concentrations of antioxidants, with the rank order as follows: lipid standardized vitamin E >> carotene = vitamin C > vitamin A, independently of classical IHD risk factors. Decreasing IHD risk through nutrition may be possible when plasma concentrations have the following values: > 27.5-30.0 mumol vitamin E/L, 0.4-0.5 mumol carotene/L, 40-50 mumol vitamin C/L and 2.2-2.8 mumol vitamin A/L. Thus, previous prudent regimens may now be updated, aiming at an optimal status of all essential and synergistically linked antioxidants. PMID- 8475898 TI - Omega-3 fatty acids: essential fatty acids with important biological effects, and serum phospholipid fatty acids as markers of dietary omega 3-fatty acid intake. AB - Serum phospholipid eicosapentaenoic (PL-EPA) and docosahexaenoic acid (PL-DHA) concentrations are associated with the dietary intake of omega 3 fatty acids. PL EPA and PL-DHA concentrations measured 4 y apart in 211 diabetic patients were highly correlated, with Spearman correlation coefficients of 0.49 (p = 0.0001) and 0.64 (p = 0.0001), respectively. PL-DHA was positively associated with Bayley psychomotor and mental developmental indexes (PDI and MDI, respectively) in preterm infants. Using multiple-regression analysis, 64% (R2 = 0.639; p = 0.0001) of PDI variance was explained by 1/DHA and weight at 1 y, whereas 82% (R2 = 0.816; p = 0.0001) of MDI variance was explained by weight at 1 y, Apgar score, 1/DHA, and 1/EPA. 1/DHA was negatively correlated with PDI and MDI, whereas 1/EPA was positively correlated with MDI. The results suggest that infant formulas should contain preformed DHA, and that a too-high supply of EPA in addition to DHA might be harmful in preterm infants. PMID- 8475899 TI - Effects of supplementation with omega 3 long-chain polyunsaturated fatty acids on retinal and cortical development in premature infants. AB - Deficiency of omega 3 long-chain polyunsaturated fatty acids (LCPUFAs) in vertebrates produces subtle adverse effects on visual and neural function. Preterm infants 1) are deprived of vital intrauterine fat accretion during late pregnancy, 2) must rely solely on formula for fatty acid supplies if not breastfed, and 3) may have limited postnatal desaturase activity. In a study to evaluate the necessity of dietary omega 3 LCPUFAs, preterm infants were fed human milk, corn-oil-based formula (omega 3 fatty acid deficient), soy-oil-based formula (rich in precursor fatty acids), or marine-oil-supplemented formula (containing docosahexaenoic acid). At 36 and 57 wk postconception, the LCPUFA profiles in red blood cell lipids were nearly equivalent in the human-milk and marine-oil groups whereas the corn-oil group had markedly lower values for omega 3 fatty acids. Rod photoreceptor function was significantly less mature in the corn-oil group compared with the human-milk and marine-oil-enriched groups in early postnatal development (36 wk). The corn-oil group also had impaired visual acuity at both 36 and 57 wk. The potential benefit of omega 3 LCPUFA-enriched full-term formula is discussed. The study supports a role for omega 3 LCPUFAs as required nutrients for the optimal maturation of visual and cortical function in preterm infants. PMID- 8475900 TI - A tribute to Dr. Henry Rappaport. PMID- 8475901 TI - Immunophenotyping of lymphomas and leukemias in paraffin-embedded tissues. PMID- 8475902 TI - Flow-cytometric DNA analysis in the diagnosis and prognosis of lymphoma. PMID- 8475903 TI - The uses of molecular biology in hematopathology. Oncogenes as diagnostic markers in non-Hodgkin's malignant lymphoma. PMID- 8475904 TI - Reactive lymphadenopathies and atypical lymphoproliferative disorders. PMID- 8475905 TI - The lymphadenopathy of HIV infection. PMID- 8475906 TI - Malignant disorders of small lymphocytes. Small lymphocytic lymphoma, lymphoplasmacytic lymphoma, and chronic lymphocytic leukemia: their clinical and laboratory relationship. PMID- 8475907 TI - Lymphomas of follicles. Mantle cell and follicle center cell lymphomas. PMID- 8475908 TI - Monocytoid B-cell lymphoma. AB - Monocytoid B-cell lymphoma is a distinct clinicopathologic entity occurring primarily in the lymph nodes of elderly patients. Its unique features compared with other low-grade lymphomas are also its characteristic morphologic features. These are its rare leukemic conversion and infrequent bone marrow involvement, and its relatively common association with autoimmune disease. Although MBCL is believed to be a low-grade, indolent type of lymphoma, its progression to high grade lymphoma warrants close follow-up of patients. PMID- 8475909 TI - Peripheral T-cell lymphoma. Morphologic and immunologic observations. PMID- 8475910 TI - Unresolved issues concerning Hodgkin's disease and its relationship to non Hodgkin's lymphoma. PMID- 8475911 TI - Composite lymphoma and related disorders. AB - Lymphomas evolve over time, usually from the small-cell to the large-cell category, and from follicular histologic characteristics to diffuse architecture. The histologic characteristics of lymphomas may be discordant in patients with multiple sites of involvement. When different types of lymphomas are encountered in a single organ or tissue, they are designated as CLs in the Working Formulation of NHL. The most common CLs consist of different subsets of follicular center cell lymphomas, usually one with low-grade follicular histologic characteristics and another with diffuse architecture and/or more aggressive cytologic features. These lymphomas now are considered to represent different phases of clonal evolution rather than representing a coincidental simultaneous occurrence of two unrelated lymphomas. Whether B-cell large-cell lymphoma coexisting with another B-cell lymphoma, namely, the nodular variant of lymphocyte-predominant Hodgkin's disease, also represents clonal evolution requires further study. Composite lymphomas consisting of a B-cell lymphoma and a T-cell lymphoma are extremely rare. The histogenetic implications for a clonal relationship between component subsets in these and other equally rare combinations remain uncertain. The CLs should continue to be recognized because (1) the component morphologic subsets may have entirely different natural histories, requiring different treatment modalities although they may be clonally related; and (2) the study of such cases may provide us with information regarding the complex interrelationship of the lymphoid system and its clonal evolution. The morphologic definition for CL of the Working Formulation should continue to be used whenever possible, with addition of appropriate immunologic and/or molecular-genetic data. PMID- 8475912 TI - Mycosis fungoides. Diagnosis and pathogenesis. PMID- 8475913 TI - Reactive histiocytic disorders. PMID- 8475915 TI - Splenic lymphoid hyperplasias versus lymphomas/leukemias. A diagnostic guide. AB - An accurate diagnosis of a lymphoid infiltrate in the spleen is based on several essential factors. 1. The spleen must be well fixed and the sections of high technical quality. 2. The pathologist has to be congnizant of the predominant distributional features, whether primarily in the white or in the red pulp, of the various lymphoid infiltrates that result in splenomegaly. 3. A differential diagnostic scheme also should be based on the predominant histologic pattern and cell type. 4. Immunophenotypic and occasionally molecular genetic studies are imperative for refinement and verification of the histologic diagnosis. PMID- 8475914 TI - Extranodal lymphoid disorders. PMID- 8475916 TI - Chronic lymphoproliferative disorders involving blood and bone marrow. PMID- 8475917 TI - Immunophenotypic analysis of acute leukemia. PMID- 8475919 TI - Pathology in the 1990s. PMID- 8475918 TI - Issues in the pathology and diagnosis of the chronic myeloproliferative disorders and the myelodysplastic syndromes. AB - We have attempted to discuss some of the issues that interest pathologists who are involved in the diagnosis of CMPD and MDS. In most cases, correlation of the clinical findings with the findings in the blood and marrow will allow the morphologist to arrive at a proper diagnosis. Nevertheless, there will continue to be cases that are difficult to classify, or in which the clinical features are out of keeping with the morphologic features. These cases are challenging and thought-provoking, and the application of newer diagnostic techniques, such as molecular genetics, may provide important insights. PMID- 8475920 TI - The reformation of Medicare and its effect on pathology. AB - Medicare policies have gradually restricted the scope of pathologist services payable under the rules applicable to physician services. Recent changes applying relative value scales has provided an opportunity for national standardization of pathology codes, and has permitted the introduction of clinical pathology interpretations as compensable physician services. PMID- 8475922 TI - Collaborative strategies for survival. AB - Pathology and laboratory medicine face major challenges, including multiplying government regulations, increasing competition, decreasing reimbursement, and loss of directorial control. Other industries facing similar threats have found solutions in a variety of collaborative strategies. Several examples of laboratory collaboration and a template for evaluation of potential joint operations are presented. Successful strategies will make it easier to handle meddlesome regulations, increase productivity and decrease costs, allow pathologists to retain control, and make the laboratory more profitable and competitive. PMID- 8475921 TI - View from Washington. Reimbursement and regulatory trends. PMID- 8475923 TI - The impact of regulatory changes on medical technology. PMID- 8475924 TI - Facing managed care's challenge to pathology. PMID- 8475925 TI - The changing relationship between clinicians and the laboratory medicine specialist in the managed care era. AB - Largely because of increased health-care costs, a variety of managed-care programs have been developed, and payment plans based on capitation will probably predominate in the future. Capitated, per-case, or per diem payment plans alter the traditional independence of health-care providers from the payment system. In these systems, clinical laboratory use becomes a resource to be managed, rather than a neutral third party or a source of income. Under capitated payment systems, clinicians will be motivated to reevaluate their own clinical laboratory resource use. Successful laboratory medicine specialists will understand these trends as well as the impact of newer payment plans on the relationship between themselves and clinicians, and develop new strategies to work with clinical colleagues to effect change. PMID- 8475926 TI - Pathophysiology and diagnosis of gastroesophageal reflux disease. AB - The pathophysiology and diagnosis of gastroesophageal reflux disease (GERD) are discussed. GERD is a clinical syndrome involving the reflux of gastric contents into the esophagus. It is distinguished from the reflux that occurs normally in the general population. A low pressure exerted by the lower esophageal sphincter (LES) and inappropriate spontaneous relaxation of the LES may contribute to the development of GERD. Other possible contributory factors are increased intra abdominal pressure and impaired esophageal clearance. The amount and concentration of refluxed gastric acid, proteolytic enzymes, and bile acids are among the determinants of the extent of esophageal injury. Heartburn is a specific symptom of GERD. Other symptoms include coughing, wheezing, hoarseness, epigastric pain, and regurgitation. Upper-GI roentgenography, endoscopy, biopsy, 24-hour ambulatory pH monitoring, and esophageal manometry have been used to diagnose and evaluate the disease. The complications of GERD are strictures, hemorrhaging, perforation, aspiration, and Barrett esophagus. The causes of GERD are incompletely understood, but low LES pressure seems important. GERD may lead to serious complications. A broad array of diagnostic approaches is available. PMID- 8475927 TI - Susceptibility of low-density lipoprotein to oxidative modification. PMID- 8475928 TI - Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. AB - PURPOSE: To test whether low-density lipoprotein (LDL) from subjects with an atherogenic lipoprotein phenotype characterized by small, dense LDL (pattern B) demonstrates greater susceptibility to oxidative modification than LDL from subjects exhibiting primarily larger, more buoyant LDL particles (pattern A). PATIENTS AND METHODS: Measures of susceptibility to oxidative modification were compared in six density subfractions of LDL isolated from pattern A and pattern B subjects. Seven male and three female pattern A subjects and five male and two female pattern B subjects, classified on the basis of peak LDL particle size, were studied. Plasma lipid and lipoprotein levels, apolipoprotein B, mean LDL particle diameter, lag phase, and rate of oxidation after initiation of oxidation by copper sulfate were measured. RESULTS: The lag time, a measure of resistance to oxidative modification, was inversely related (p < 0.001) to LDL density in both groups of subjects, without an independent effect of phenotype. The fraction that had the major LDL peak had a shorter lag time (p < 0.05) in pattern B than in pattern A. Pattern B subjects also demonstrated an increased rate of oxidation (p < 0.005) in fraction 1, which includes remnants of triglyceride-rich lipoproteins. CONCLUSIONS: The increased atherogenic risk associated with the pattern B phenotype may result in part from increased concentrations of lipoprotein subpopulations that are relatively susceptible to oxidative modification. PMID- 8475929 TI - Risk of human immunodeficiency virus infection among emergency department workers. AB - PURPOSE: To estimate (1) the prevalence of human immunodeficiency virus (HIV) infection in emergency department (ED) patients, (2) the frequency of blood contact (BC) in ED workers (EDWs), (3) the efficacy of gloves in preventing BC, and (4) the risk of HIV infection in EDWs due to BC. PATIENTS AND METHODS: We conducted an 8-month study in three pairs of inner-city and suburban hospital EDs in high AIDS incidence areas in the United States. At each hospital, blood specimens from approximately 3,400 ED patients were tested for HIV antibody. Observers monitored BC and glove use by EDWs. RESULTS: HIV seroprevalence was 4.1 to 8.9 per 100 patient visits in the 3 inner-city EDs, 6.1 in 1 suburban ED, and 0.2 and 0.7 in the other 2 suburban EDs. The HIV infection status of 69% of the infected patients was unknown to ED staff. Seroprevalence rates were highest among patients aged 15 to 44 years, males, blacks and Hispanics, and patients with pneumonia. BC was observed in 379 (3.9%) of 9,793 procedures; 362 (95%) of the BCs were on skin, 11 (3%) were on mucous membranes, and 6 (2%) were percutaneous. Overall procedure-adjusted skin BC rates were 11.2 BCs per 100 procedures for ungloved workers and 1.3 for gloved EDWs (relative risk = 8.8; 95% confidence interval = 7.3 to 10.3). In the high HIV seroprevalence EDs studied, 1 in every 40 full-time ED physicians or nurses can expect an HIV-positive percutaneous BC annually; in the low HIV seroprevalence EDs studied, 1 in every 575. The annual occupational risk of HIV infection for an individual ED physician or nurse from performing procedures observed in this study is estimated as 0.008% to 0.026% (1 in 13,100 to 1 in 3,800) in a high HIV seroprevalence area and 0.0005% to 0.002% (1 in 187,000 to 1 in 55,000) in a low HIV seroprevalence area. CONCLUSIONS: In both inner-city and suburban EDs, patient HIV seroprevalence varies with patient demographics and clinical presentation; the infection status of most HIV-positive patients is unknown to ED staff. The risk to an EDW of occupationally acquiring HIV infection varies by ED location and the nature and frequency of BC; this risk can be reduced by adherence to universal precautions. PMID- 8475930 TI - Attempts to eradicate methicillin-resistant Staphylococcus aureus from a long term-care facility with the use of mupirocin ointment. AB - PURPOSE: To assess the impact of the use of mupirocin ointment on colonization, transmission, and infection with methicillin-resistant Staphylococcus aureus (MRSA) in a long-term-care facility. PATIENTS AND METHODS: All 321 residents of a Veterans Affairs long-term-care facility from June 1990 through June 1991 were studied for MRSA colonization and infection. MRSA-colonized patients received mupirocin ointment to nares in the first 7 months and to nares and wounds in the second 5 months. The effect of mupirocin use on MRSA colonization and infection was monitored. All S. aureus strains isolated were tested for the development of resistance to mupirocin. RESULTS: A total of 65 patients colonized with MRSA received mupirocin ointment. Mupirocin rapidly eliminated MRSA at the sites treated in most patients by the end of 1 week. Weekly maintenance mupirocin was not adequate to prevent recurrences--40% of patients had recurrence of MRSA. Overall, MRSA colonization in the facility, which was 22.7% +/- 1% prior to the use of mupirocin, did not change when mupirocin was used in nares only (22.2% +/- 2.1%), but did decrease to 11.5% +/- 1.8% when mupirocin was used in nares and wounds. Although colonization decreased, roommate-to-roommate transmission and MRSA infection rates, low to begin with, did not change when mupirocin was used. Mupirocin-resistant MRSA strains were isolated in 10.8% of patients. CONCLUSIONS: Mupirocin ointment is effective at decreasing colonization with MRSA. However, constant surveillance was required to identify patients colonized at admission or experiencing recurrence of MRSA during maintenance treatment. Long-term use of mupirocin selected for mupirocin-resistant MRSA strains. Mupirocin should be saved for use in outbreak situations, and not used over the long term in facilities with endemic MRSA colonization. PMID- 8475931 TI - Infarct site-related mortality in patients with recurrent myocardial infarction. SPRINT Study Group. AB - PURPOSE: The purpose of this study was to determine the effect of acute and old myocardial infarction (MI) sites on early (15 days) mortality in patients with a second MI. PATIENTS AND METHODS: Data are derived from the SPRINT 2 study population that included 1,161 consecutive patients with acute MI, aged 50 to 79 years, recruited from 14 coronary care units in Israel between November 1985 and July 1986. Two hundred twenty-six of these patients (19.5%) had a previous MI prior to the index acute MI. Sixty-two patients were excluded from the analysis either because the MI site was not of anterior or inferior location, or because of incomplete data. In the 164 (73%) remaining patients, acute and old MI locations were determined to be either anterior or inferior and were accordingly divided into 4 groups: acute anterior-old anterior (Group 1-23 patients); acute anterior-old inferior (Group 2-86 patients); acute inferior-old anterior (Group 3 34 patients); acute inferior-old inferior (Group 4-21 patients). RESULTS: Significant differences in clinical parameters among the four groups included a higher proportion of Q-wave MI (p = 0.04), severe congestive heart failure during admission (p = 0.04), and markedly elevated serum lactate dehydrogenase levels (p = 0.05) in Group 3. High-degree atrioventricular block (p = 0.001) and cardiogenic shock (p = 0.05) also developed more often in this group during hospitalization. Twenty-three patients (14%) died within 15 days. Death rates in the acute anterior (Group 1 plus Group 2) and the acute inferior (Group 3 plus Group 4) groups were 11% versus 20%, respectively (NS). However, death rate variability across the four groups was statistically significant (p = 0.018), with the highest mortality observed in Group 3 (old anterior-acute inferior MI 29%). Multivariate analysis identified acute inferior MI following old anterior MI as a strong independent predictor of early death (relative odds vis-a-vis other combinations 5.0, 95% confidence interval 1.5 to 16.6). CONCLUSION: This study identifies a subgroup of patients with acute inferior MI at high risk for early mortality. It is possible that such patients would benefit from early reperfusion therapy. PMID- 8475932 TI - Circadian variation and possible external triggers of onset of myocardial infarction. SPRINT Study Group. AB - PURPOSE: To determine whether a circadian pattern in onset of symptoms existed and possible external triggers were implicated in the precipitation of acute myocardial infarction (AMI). PATIENTS AND METHODS: One thousand eight hundred eighteen consecutive patients with AMI hospitalized in 14 of the 21 existing coronary care units in Israel during the study period were assessed. RESULTS: The frequency of onset of symptoms by 6-hour intervals showed a predominant morning peak (6 AM to noon) (32%, p < 0.01) in comparison with the other three 6-hour intervals of the day. The preponderance of the morning peak persisted for subgroup analysis by gender (males 32%, females 31%); age (less than or equal to 65 years--32%; greater than 65 years--33%); diabetes mellitus (present or absent, 32%). However, patients with peripheral vascular disease and those with stroke in the past had a predominant evening peak. Possible external triggers of onset of AMI were present in 10% of patients. Exceptional heavy physical work, violent quarrel at work or at home, and unusual mental stress were the three most frequent possible external triggers reported immediately before or within the 24 hours preceding pain onset. Patients with possible external triggers were more likely to be males (85%) and were somewhat but not significantly younger (63.1 years) in comparison with patients without external triggers (73% and 64.3 years respectively). CONCLUSIONS: In a large group of consecutive patients with AMI, a predominant cyclic morning peak of pain onset was found in comparison with the other hours of the day. Possible external triggers precipitating AMI were involved in a minority of cases, suggesting that endogenous changes occurring in the morning hours are generally responsible for the increased rate of myocardial infarction occurring after awakening. PMID- 8475933 TI - Genetic predisposition to hypertension facilitates blood pressure elevation in hemodialysis patients treated with erythropoietin. AB - PURPOSE: This study investigated the hypothesis that a genetic predisposition to hypertension is involved in the etiology of the elevation in blood pressure induced by human recombinant erythropoietin (rHuEPO). PATIENTS AND METHODS: Blood pressure changes after 10 weeks of treatment with rHuEPO were compared between 26 patients with a positive family history of hypertension and 27 with a negative family history. RESULTS: Mean blood pressure was significantly increased in patients with a positive family history of hypertension (+8.8 mm Hg, p < 0.001). In contrast, the change was not significant in those whose family history was negative (+1.8 mm Hg, not significant). The mean blood pressure of 14 of 26 patients with a positive family history of hypertension increased by more than 10%, whereas such an increase occurred in only 2 of 27 patients with a negative family history (p < 0.001). The two groups were similar in terms of the total dose of rHuEPO given, the degree to which their anemia improved, and their basal blood pressures. CONCLUSION: It appears that hemodialysis patients with a positive family history of hypertension are susceptible to developing hypertension during treatment with rHuEPO. PMID- 8475934 TI - Hemodynamic effects of altitude exposure and oxygen administration in chronic obstructive pulmonary disease. AB - PURPOSE: Cardiovascular events are the leading cause of death during air travel. Because patients with chronic obstructive pulmonary disease (COPD) develop severe hypoxemia at altitude, we sought to determine whether changes in systemic hemodynamics may contribute to health risks during hypobaric hypoxia. PATIENTS AND METHODS: We recorded radial artery catheter blood pressure, cardiac frequency, and cardiac ectopy in 18 men (aged 68 +/- 6 years, mean +/- SD) with severe COPD (forced expiratory volume in 1 second 0.97 L +/- 0.32 L) at sea level, after 45 minutes of steady-state hypobaric hypoxia at 2,438 m in a hypobaric chamber, and after oxygen supplementation at 2,438 m. RESULTS: Mean arterial pressure (mm Hg), systolic blood pressure (SBP), diastolic blood pressure, and pulsus paradoxus during acute hypobaric exposure did not differ from baseline. During oxygen supplementation, SBP declined (p = 0.028). Decreases in pulsus paradoxus and pulse pressure were noted on oxygen (p < 0.05). We found no changes in cardiac frequency. Cardiac ectopy was uncommon; for one subject, ectopy increased with hypobaric hypoxia and decreased with oxygen administration. CONCLUSION: Vasopressor responses to hypoxia do not add to the risk of air travel in patients with severe COPD. Supplemental oxygen may cause beneficial hemodynamic changes in patients with COPD during acute hypobaric exposure. PMID- 8475935 TI - Ulcer risk factors: interactions between Helicobacter pylori infection, nonsteroidal use, and age. AB - PURPOSE: To evaluate the influence of Helicobacter pylori, nonsteroidal anti inflammatory drug (NSAID) use, tobacco and alcohol use, age, gender, ethnic group, and the indication for endoscopy on the frequency of gastric and duodenal ulcers in patients referred for upper endoscopy. PATIENTS AND METHODS: One thousand eighty-eight consecutive patients without prior antrectomy or active bleeding at endoscopy who were able to provide a history were interviewed prior to endoscopy, and antral biopsies were performed for H. pylori at endoscopy. Variables were tested for univariate association with duodenal or gastric ulcer and those variables with p < 0.25 were included in the logistic regression model building. RESULTS: One hundred seven patients had duodenal ulcer, 97 had gastric ulcers, and 5 had both. Significant risk factors in the final model for duodenal ulcer were H. pylori, history of previous ulcer, male gender, bleeding, and pain at presentation (p < 0.001), whereas alcohol was associated with a decreased risk (p = 0.026). H. pylori presence (p = 0.011), aspirin use (p = 0.009), and bleeding (p = 0.012) were associated with gastric ulcer in the final model; esophageal symptoms were associated with decreased risk of gastric ulcer (p = 0.003). NSAID use was associated with gastric ulcers only in those over 55 (p < 0.05), especially whites, and in nonwhites without prior ulcer. There was no interaction between H. pylori and NSAIDs. CONCLUSIONS: H. pylori was associated with an increased risk of duodenal and gastric ulcers. Aspirin increases the risk for gastric ulcer in patients of all ages, whereas nonaspirin, nonsteroidal use increases the risk for gastric ulcers to varying degrees in patients over age 55, depending on race and history of ulcer. PMID- 8475936 TI - Effect of nifedipine on physiologic shunting and oxygenation in chronic obstructive pulmonary disease. AB - PURPOSE: To assess changes in physiologic shunting and oxygenation following short-term treatment with nifedipine in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease. PATIENTS AND METHODS: Changes in pulmonary vascular pressure, pulmonary vascular resistance, venous admixture, and systemic arterial oxygen tension following sublingual administration of 20 mg of nifedipine were studied in 18 patients (13 men, 5 women; mean age of 59.7 [SD 7.2] years) using Swan-Ganz catheterization. These patients had a mean peak expiratory flow rate of 112 (SD 27) L/min (mean 22.2 [SD 12.2]% of predicted value), mean forced expiratory volume in 1 second (FEV1) of 0.84 (SD 0.23) L (mean 31.2 [SD 8.5]% of predicted value), mean FEV1/forced vital capacity ratio of 31.6 (SD 4.5), and mean carbon monoxide diffusing capacity of 6.8 (SD 1.96) mmol/min/kPa. RESULTS: There was a significant decrease in mean pulmonary vascular resistance (562 to 371 dyne sec.cm-5) and a significant reduction in the mean pulmonary arterial pressure (mean 32.8 to 23.6 mm Hg). Pulmonary venous admixture, however, increased significantly from the baseline mean of 44.6% (SD 16.1) to a mean of 56% (SD 15.6), and the mean arterial oxygen tension decreased from 5.8 (SD 1.3) kPa to 4.5 (SD 0.8) kPa at 60 minutes following drug administration (p < 0.001). CONCLUSION: The role of nifedipine in the treatment of pulmonary hypertension secondary to chronic bronchitis may be limited because of its deleterious effect on venous admixture. PMID- 8475937 TI - Thyroid hormone resistance syndromes. AB - The thyroid hormone resistance syndromes are disorders in which the body's tissues are resistant to the effects of thyroid hormone. Generalized resistance to thyroid hormone (GRTH) is characterized by resistance in the pituitary gland and in most or all of the peripheral tissues. Affected individuals have elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid stimulating hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary resistance to thyroid hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues. Patients have elevated serum thyroid hormone levels and normal or elevated TSH levels and are clinically thyrotoxic. Therapy is usually necessary, but current choices are not completely satisfactory. Selective peripheral resistance to thyroid hormone (PerRTH) is characterized by resistance in peripheral tissues but not in the pituitary. The only patient thus far described had normal serum thyroid hormone and TSH levels but was clinically hypothyroid and improved with thyroid hormone administration. All of these disorders are probably more common than is generally recognized and are often misdiagnosed and inappropriately treated. GRTH, in most cases studied, results from a mutation in the thyroid hormone receptor beta gene causing an amino acid substitution in or a partial or complete deletion of the thyroid hormone-binding domain of the receptor. The causes of PRTH and PerRTH remain to be determined. PMID- 8475938 TI - Spontaneous splenic rupture complicating anticoagulant or thrombolytic therapy. AB - PURPOSE: To characterize the clinical course and outcomes of reported cases of splenic hemorrhage during thrombolytic or anticoagulant therapy. METHODS: The Medline, EMBASE (Excerpta Medica), BIOSIS, and SCISEARCH databases for English and foreign literature between 1966 and 1991 were searched. All reports of patients with documented splenic hemorrhage during anticoagulant therapy or thrombolytic therapy were reviewed. Foreign language manuscripts were translated into English. RESULTS: Seventeen cases of splenic hemorrhage associated with anticoagulant or thrombolytic therapy were found. In one case, there was minor antecedent trauma; in the remaining cases, hemorrhage was spontaneous. Mortality overall was 24% and was more likely in patients with splenic hemorrhage after thrombolytic therapy (50%) than in patients receiving long-term anticoagulants (9%). Splenectomy was performed in 12 of 13 survivors. CONCLUSIONS: Splenic hemorrhage associated with anticoagulant or thrombolytic therapy is a rare entity. It may be lethal, especially when associated with lytic therapy. Reversal of the anticoagulated or lytic state and emergent splenectomy are the treatment of choice. Splenic hemorrhage can mimic acute myocardial infarction and cardiogenic shock and must be considered when the condition of cardiac patients receiving lytic or anticoagulant drugs suddenly deteriorates. PMID- 8475939 TI - Net worth. PMID- 8475940 TI - Reversible parkinsonism and asymptomatic hypocalcemia with basal ganglia calcification from hypoparathyroidism 26 years after thyroid surgery. PMID- 8475941 TI - Strongyloides hyperinfection in patients coinfected with HTLV-I and S. stercoralis. PMID- 8475942 TI - Rhabdomyolysis and hypophosphatemia. PMID- 8475943 TI - Treatment of Wilson's disease with zinc XII: dose regimen requirements. AB - A considerable body of data is now available indicating the efficacy and lack of toxicity of zinc treatment of Wilson's disease. Dose-response studies have shown that regimens of 50 mg of elemental zinc 3 times a day (50 mg x 3), 25 mg x 3, and 50 mg x 2 are effective, but 25 mg x 2 and 50 mg x 1 are not adequately effective. These studies indicate that 75 mg a day is close to the minimally effective dose, but do not address the question of necessary dose frequency. In the current study, the authors have used the minimally effective daily dose, 75 mg, and studied this daily dose in regimens of 25 mg x 3, 37.5 mg x 2, and 75 mg x 1 in treatment of four patients with Wilson's disease. These data have been supplemented with additional data from 11 patients treated with 25 mg 3 times a day and with data from 2 patients treated with 75 mg once a day. Efficacy was evaluated by 10-day copper balance and absorption of orally administered 64copper. The findings indicate that a daily dose of 75 mg must be divided into at least two doses to be effective, and that the 64copper procedure is more sensitive to zinc dose than copper balance. PMID- 8475944 TI - Differential responses of human papillary and reticular fibroblasts to growth factors. AB - Differences in the responses to growth factors of normal fibroblasts and scleroderma fibroblasts have been demonstrated previously. Because human dermal fibroblasts are heterogeneous populations, whether known differences between papillary and reticular dermal fibroblasts could account for the noted differences between normal and scleroderma fibroblasts was investigated. Papillary dermal fibroblasts were grown from a dermatome section of normal skin from an adult donor. Reticular dermal fibroblasts were cultured from punch biopsy specimens taken from the same location. In vitro, papillary dermal fibroblasts proliferated more rapidly, had a higher mitotic index and reached greater density at confluence, confirming previous observations. The reticular dermal fibroblasts were more dendritic. Reticular dermal fibroblasts had higher rates of tritiated thymidine uptake and larger increases in mitotic index in response to isoforms of platelet-derived growth factor (PDGF). The characteristic response of scleroderma fibroblasts, potentiation of the mitogenicity of PDGF AA by transforming growth factor-beta (TGF-beta), was not observed in either cell type. Therefore, the phenotypic characteristics of scleroderma fibroblasts cannot be explained by an unusual admixture of papillary and reticular fibroblasts. PMID- 8475945 TI - Heparin-associated thrombocytopenia: a critical review and pooled analysis. AB - The purpose of this study is to determine the incidence of heparin-associated thrombocytopenia (HAT) for various subgroups of heparin exposed patients and the impact of study quality on the reported incidence. Articles were identified using a Medline search, a manual search of the Index Medicus, and a review of article references. Key data included heparin type, administration route, indication, treatment duration, outcome criteria, incidence, and platelet count reliability. The pooled incidence estimate in studies requiring a repeatedly abnormal platelet count was compared with estimates from studies not requiring a repeated platelet count. The results showed that there were no adequately designed studies to estimate the incidence of HAT-related thrombosis or hemorrhage. The pooled incidence of HAT in studies requiring a reproducibly lowered platelet count (< 100,000/microL) was 3/281 (1.1%) with intravenous porcine heparin and 4/140 (2.9%) with intravenous bovine heparin. This difference was not statistically significant. The incidence of HAT with intravenous bovine heparin was significantly lower in studies that required a repeated platelet count. The incidence of HAT with heparin administered subcutaneously was small (0%) and in those studies requiring a repeatedly abnormal platelet count, there was no difference between porcine and bovine heparin. The authors concluded that the incidence of HAT is < 3% with intravenous heparin and extremely low for subcutaneous heparin. Study quality may influence the reported incidence of HAT. PMID- 8475946 TI - Effects of enalapril on ventricular volumes and neurohumoral status after inferior wall myocardial infarction. AB - The activation of the sympathetic nervous system and the renin-angiotensin aldosterone system and its beneficial modification with the use of angiotensin converting enzyme inhibin after inferior wall myocardial infarction (MI) was evaluated. Fifty patients with acute inferior MI were randomly assigned to receive 5 mg per day of either enalapril or placebo after admission. Blood tests for neurohormone levels and echocardiograms were performed at initial examination and 4 weeks later. Baseline characteristics were similar in the two groups. Four weeks after randomization, patients treated with enalapril had lower end diastolic volume (146 +/- 29 vs 167 +/- 15 ml; p = 0.04), end-systolic volume (56 +/- 18 vs 107 +/- 17 ml; p = 0.03), serum norepinephrine levels (320 +/- 93 vs 465 +/- 77 pg/ml; p < 0.01), angiotensin II levels (18 +/- 6 vs 54 +/- 11 pg/ml; p < 0.01), and atrial natriuretic polypeptide levels (106 +/- 9 vs 122 +/- 17 pg/ml; p = 0.05) than patients given placebo. The incidence of heart failure after MI was also lower in this group (4% vs 16%; p = 0.009). Results show that there is early neurohumoral activation in the course of acute inferior wall MI. Enalapril reduces neurohumoral levels and preserves ventricular volumes. These effects were associated with a reduction in the incidence of heart failure 4 weeks after MI in these patients. PMID- 8475947 TI - Use of the Rand Structured Implicit Review Instrument for Quality of Care Assessment. AB - The Rand Structured Implicit Review Instrument is a 27-item instrument that rates process quality of care for patients with five common illnesses. This study reports on the use of this instrument for hospitalized patients with long lengths of stay. A total of 120 medical records were reviewed by multiple physician reviewers for patients discharged with congestive heart failure, acute myocardial infarction, and pneumonia. Mean inter-rater reliability was assessed for a subsample of six records by kappa score. A multiple regression analysis was used to estimate the relationship between process ratings for the quality of documentation, assessment, monitoring, and therapy and overall quality of care scores, controlled for physician judgments about patients' prognosis and selected patient characteristics. Each reviewer also evaluated the instrument. Mean kappa for trichotomized ratings of quality of care was 0.50. The majority of all quality of care ratings were in the good or very good range (77.5%). The full regression model, including process subscale quality ratings, prognostic items, and patient characteristics, accounted for 38% of the total variance in the quality of care ratings. Items measuring the quality of assessment (p < 0.0001), therapy (p < 0.02) and monitoring (p < 0.01) were significant. Physicians accepted the use of such a form moderately well. The Rand quality of care form shows consistency in rating overall quality of care and individual dimensions of quality. Achieving a high level of inter-rater reliability is difficult with implicit review. By focusing on specific areas of potentially deficient care, structured review instruments can improve clinical quality improvement efforts. PMID- 8475948 TI - Case report: gastric angiolipoma with chronic hemorrhage and severe anemia. AB - Lipomas are benign tumors that are common in other sites but rare in the stomach. They are usually submucosal and, when symptomatic, are most often accompanied by gastrointestinal hemorrhage. Angiolipoma is a not uncommon benign lipomatous neoplasm with a characteristic vascular component that almost exclusively occurs in the subcutaneous tissue. A case of gastrointestinal angiolipoma, which appears to be only the second one reported, is discussed. The patient, a 69-year-old man, presented with signs and symptoms of chronic hemorrhage and severe anemia (hemoglobin 6, hematocrit 19.9). The patient's condition was found to have resulted from ulceration of the gastric mucosa overlying a submucosal angiolipoma, and the anemia resolved after local surgical resection of the tumor. Electron microscopic studies supported the light microscopic diagnosis of angiolipoma. The absence of fibrin thrombi in this and other nonsubcutaneous angiolipomas and the possible significance of the vascularity of these tumors is discussed. The literature regarding gastric lipoma and angiolipoma is reviewed. PMID- 8475949 TI - Case report: pentamidine and polymorphic ventricular tachycardia revisited. AB - Pentamidine isethionate has been associated with ventricular tachyarrhythmias, including torsade de pointes. This article reports two cases of this complication and reviews all reported cases to date. Pentamidine-induced torsade de pointes may be related to serum magnesium levels and hypomagnesemia may synergistically induce torsade. Torsade de pointes occurred after an average of 10 days of treatment with pentamidine. In these patients, no other acute side effects of pentamidine were observed. Torsade de pointes can be treated when recognized early, possibly without discontinuation of pentamidine. When QTc interval prolongation is observed, early magnesium supplementation is advocated. PMID- 8475950 TI - Lead nephropathy, gout, and hypertension. AB - The EDTA (calcium disodium edetate) lead mobilization test revealed lead as the probable cause of renal disease in industrial lead workers and in patients with gout or essential hypertension. The data reviewed here demonstrate persistence of lead nephropathy in the contemporary scene despite the introduction of modern industrial and environmental exposure standards. Renal function and biopsy studies showed that lead nephropathy is a chronic tubulointerstitial renal disease with modest proteinuria which frequently presents with hyperuricemia, gout and hypertension. Only evaluation of body lead stores by either the EDTA lead mobilization test or by x-ray fluorescence is helpful in diagnosing lead nephropathy. While chelation therapy is safe and helpful in reversing early lead nephropathy, the best treatment is prevention. These studies further raise the possibility that chronic environmental lead poisoning and associated renal disease and hypertension may be a more widespread problem than suspected. Assessment of the true extent of chronic lead poisoning requires large scale epidemiological studies. PMID- 8475951 TI - Not to decide is to decide. PMID- 8475952 TI - Specialization in obstetrics and gynecology--changing standards. PMID- 8475953 TI - Bright seashells on the sand. AB - In obstetrics and gynecology residency education is a fixed prescription, whereas the world of practice leads physicians in diverse directions. Nonetheless, obstetrics and gynecology has so far resisted the proliferation of subspecialties. The future scope of our specialty will be defined by the changing healthcare needs of women. These will be driven by changing demographics and an emphasis on preventive and primary care. Residency education and, to a lesser extent, forms of practice will have to change to meet women's needs. PMID- 8475954 TI - Cystic fibrosis mutations in white and black Americans: an approach to identification of unknown mutations with implications for cystic fibrosis screening. AB - OBJECTIVE: We sought to define the frequency of common cystic fibrosis mutations in white and black American probands from our geographic region. STUDY DESIGN: Mutation analysis was performed for delta F508, G551D, G542X, R553X, S549N, an d N1303K. For probands with undetermined mutations single-stranded conformational polymorphism analysis was performed. RESULTS: Among 40 white subjects with cystic fibrosis 26 (65%) were homozygous for delta F508, 10 (25%) were heterozygous for delta F508 and another unknown mutation, and two were homozygous for unknown mutations. Among 10 black probands one was homozygous for delta F508, seven (70%) were heterozygous for delta F508 and another unknown mutation, and one was homozygous for unknown mutations. Single-stranded conformational polymorphism analysis for selected exons was performed for 11 probands with unknown mutations. One mutation was detected in a white proband. Sequencing of this exon showed the mutation to be Q493X. CONCLUSIONS: Thirty percent of white subjects and 80% of black subjects carried unknown mutations. In one family single-stranded conformational polymorphism was informative in identifying an undetermined cystic fibrosis mutation. PMID- 8475955 TI - Low-dose aspirin therapy to prevent preeclampsia. AB - OBJECTIVE: Our aim was to test the hypothesis that acetylsalicylate (aspirin) treatment reduces the incidence or severity of pregnancy-associated hypertension. STUDY DESIGN: Patients were nulliparous, healthy, and with a singleton gestation at between 20 and 22 weeks' gestation. A sample size of 600 patients was calculated on the basis of p < or = 0.05 and 90% power of observation. A 2-week placebo-controlled "run-in" was used to select compliant patients. Randomization occurred at 24 weeks, with 60 mg of aspirin or placebo treatment from randomization to delivery. RESULTS: Follow-up was maintained on 99% of the patients. The randomized patients had a 94% pill compliance index. At randomization, serum thromboxane medians were similar in both groups. Thromboxane B2 levels in the aspirin group decreased significantly from baseline at 29 to 31 weeks, 34 to 36 weeks, and at delivery as compared with an overall increase in the placebo group. Preeclampsia developed in five of 302 women (1.7%) who received aspirin versus 17 of 302 (5.6%) who received the placebo (p = 0.009). Preeclampsia was severe in one aspirin and in six placebo recipients (p = 0.06). CONCLUSION: Daily ingestion of 60 mg of aspirin beginning at 24 weeks' gestation significantly reduced the occurrence of preeclampsia. PMID- 8475956 TI - Maternal caffeine consumption and fetal behavior in normal third-trimester pregnancy. AB - OBJECTIVE: Our aim was to perform a longitudinal cohort study of 20 normal third trimester pregnancies to observe whether the level of long-term maternal caffeine ingestion influenced fetal behavior. STUDY DESIGN: By dietary history 10 normal pregnant women were categorized as "high" caffeine consumers (> 500 mg/day, group H) and 10 as "low" caffeine consumers (> 200 mg/day, group L). Between 30 and 40 weeks biweekly 2-hour continuous ultrasonographic observations of fetal heart rate; breathing activity; and eye, trunk, and extremity movements were conducted. Maternal caffeine levels were determined at each session, and fetal states were identified and their duration quantified. Data were compared by analysis of variance by means of repeated measures or t tests. RESULTS: When compared with group L fetuses, group H fetuses spent similar mean time in state 1F (quiet sleep), less mean time in state 2F (active sleep), and much greater mean time in state 4F (arousal). The mean time spent in no state decreased significantly in group L, was unchanged in group H, and was similar for both groups at term. Both groups had similar mean numbers of state changes at all gestational ages studied. Mean maternal serum caffeine levels in group H were always significantly higher than those in group L. CONCLUSION: Evolving fetal behavior may be influenced by the level of maternal caffeine consumption during the last trimester. PMID- 8475957 TI - Acute hemodynamic and respiratory effects of amniotic fluid embolism in the pregnant goat model. AB - OBJECTIVE: Our purpose was to determine the acute-phase central hemodynamic and respiratory effects of raw, filtered, filtered and boiled, and meconium containing amniotic fluid. STUDY DESIGN: Pregnant goats (Capra hircus) in the last one third of pregnancy were given freshly collected autologous amniotic fluid in a volume of 2.5 ml/kg of body weight. Observations were then made at 10, 30, 60, 120, and 180 minutes after amniotic fluid embolism. Pulmonary artery catheters and femoral artery lung water catheters were placed for specimen and data collection. RESULTS: Marked pressor responses were observed in both the pulmonary and systemic circulations with all amniotic fluid infusions. The pressor response was similar with raw, filtered, and filtered and boiled amniotic fluid. The pressor response seen with amniotic fluid containing meconium was significantly greater than that seen with the other forms. No significant effects were observed on cardiac or respiratory function except in the meconium group, where transient left ventricular dysfunction was accompanied by an acute increase in extravascular lung water and dysoxia. CONCLUSIONS: The Capra hircus model is appropriate for the further study of amniotic fluid embolism. The acute pressor effects are transient and involve both the systemic and pulmonary circulations. Left ventricular dysfunction and dysoxia were observed only with embolism of amniotic fluid containing meconium. PMID- 8475958 TI - The effect of growth factors on the proliferation of human endometrial stromal cells in culture. AB - OBJECTIVE: Development of ectopic implants of endometriosis is associated with both an inflammatory response by macrophages and endometrial stromal cell proliferation. Macrophages are capable of releasing a variety of inflammatory mediators, including growth factors. To assess the impact of such factors on endometrial tissue, we have studied the effects of recombinant growth factors, fibroblast growth factor, epidermal growth factor, transforming growth factor alpha, and inflammation mediators transforming growth factor-beta, and tumor necrosis factor-alpha on human endometrial stromal cell proliferation. STUDY DESIGN: Increasing concentrations of these compounds were added to cultures of primary, secondary, and long-term stromal cells and the cells were harvested at 24, 48, and 72 hours. RESULTS: Epidermal growth factor, transforming growth factor-alpha, transforming growth factor-beta, and fibroblast growth factor induced a statistically significant, dose-dependent increase in stromal cell thymidine uptake of 1.5- to fivefold. The cytokine tumor necrosis factor had no effect alone, but the combination of fibroblast growth factor and tumor necrosis factor had a synergistic effect, increasing cell proliferation 25% to 84% over fibroblast growth factor alone. CONCLUSION: The stromal cell response to a wide range of cell growth effectors and the potential of mediators like tumor necrosis factor-alpha to synergize suggest that such macrophage-secretory products may contribute to proliferation of endometrial implants in vivo. PMID- 8475959 TI - Gestational diabetes: predictors of subsequent disordered glucose metabolism. AB - OBJECTIVE: We tested the hypothesis that the development of abnormal glucose metabolism after gestational diabetes can be predicted readily by means of available clinical variables. STUDY DESIGN: Three hundred fifty nonpregnant former gestational diabetic women delivered during the previous 10 years underwent glucose tolerance tests. Variables including body mass index before the index pregnancy, pregnancy glucose tolerance test values, gestational diabetes treatment, complications, gestational age at diagnosis of gestational diabetes, and time elapsed since pregnancy were analyzed with logistic regression. RESULTS: Variables that distinguished subjects who later developed diabetes or impaired glucose tolerance included prepregnancy body mass index (28.5 +/- 7 versus 25 +/- 5 kg/m2, p < 0.001) and fasting glucose on the pregnant oral glucose tolerance test (109 +/- 20 vs 92 +/- 15 mg/dl, p < 0.001). Logistic results with these two variables plus time since the index pregnancy predict subsequent glucose tolerance test abnormality by the following equation: estimated risk = 1/[1 + e-( 10.37 + 0.04 (fasting plasma glucose) + 0.08 (body mass index) + 0.03 (months since delivery))]. CONCLUSION: The risk for subsequent glucose abnormality among individuals with previous gestational diabetes is quantifiable based on prepregnant body mass index and fasting plasma glucose during pregnancy. PMID- 8475960 TI - A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery. AB - OBJECTIVE: Our aim was to determine the relative efficacy and complications of low-dose heparin and intermittent pneumatic calf compression for the prevention of postoperative venous thrombosis in patients undergoing surgery for gynecologic malignancy. STUDY DESIGN: Randomized trial comparing 107 patients treated with low-dose heparin to 101 patients treated with intermittent pneumatic calf compression was performed. All patients were evaluated with iodine-125 fibrinogen scanning of the legs. Clinical and laboratory variables associated with bleeding complications were recorded prospectively. RESULTS: Venous thrombosis was diagnosed in seven patients receiving low-dose heparin and in four receiving intermittent pneumatic calf compression (p = 0.54). Low-dose heparin patients received more blood transfusions postoperatively (p = 0.02), had increased volume of retroperitoneal drainage (p = 0.02), and the activated partial thromboplastin time was more frequently prolonged (p = 0.001). CONCLUSIONS: Low-dose heparin and intermittent pneumatic calf compression provide similar reduction in reducing the incidence of postoperative venous thrombosis. However, low-dose heparin is more frequently associated with postoperative bleeding complications. PMID- 8475961 TI - Adaptive immune responses during murine pregnancy: pregnancy-induced regulation of lymphokine production by activated T lymphocytes. AB - OBJECTIVE: We hypothesized that the lymphokine production by splenocytes and decidual lymphocytes would be altered because of changes in immunoregulation during pregnancy. STUDY DESIGN: Splenocytes and decidual lymphocytes were isolated from syngeneic and allogeneic pregnant mice at different times of gestation. The lymphocytes (10(7) cells/ml) were stimulated with anti-CD3 antibody, and culture supernatants were assayed for several lymphokines, including interleukin-2, interferon-gamma, interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3. Statistical analysis was by analysis of variance or paired t test. RESULTS: Activated splenocytes produced significantly less interleukin-2 and more interleukin-4, interleukin-6, and interleukin-3 as murine pregnancy advanced. Production of interferon-gamma and granulocyte macrophage colony-stimulating factor by activated splenocytes peaked in the first 8 to 14 days of pregnancy. Stimulated decidual lymphocytes produced modest amounts of interleukin-6, granulocyte macrophage colony-stimulating factor, and interleukin-3 during pregnancy but no interleukin-2, interferon-gamma, or interleukin-4. Similar results were found for both syngeneic and allogeneic matings. CONCLUSIONS: Our findings indicate that splenocyte lymphokine production favors interleukin-4 production over interleukin 2 production. This finding suggests that antibody production would be enhanced and cytotoxic cellular immune responses inhibited during pregnancy. These changes occurred regardless of mating partner, suggesting that the specific antigenic stimulus during normal pregnancy does not regulate lymphokine production. Activated splenocytes and decidual lymphocytes were found to differ in their capacity to produce lymphokines, indicating that the decidua constitutes a distinct and unique immunologic microenvironment. PMID- 8475962 TI - The effect of acetaminophen on prostacyclin production in pregnant women. AB - OBJECTIVE: The purpose of this study was to determine if acetaminophen decreased prostacyclin production by endothelial cells in culture and by pregnant women. STUDY DESIGN: The effect of acetaminophen on endothelial cells in culture was determined by the addition of acetaminophen in concentrations of 10 and 100 micrograms/ml with comparison to control and indomethacin at 10 micrograms/ml. Prostacyclin production was estimated in 24 and thromboxane A2 production in six third-trimester pregnant women by measurement of excretion of urinary metabolites before and after ingestion of either 1000 mg of acetaminophen or placebo. RESULTS: Compared with control (549 +/- 61 pg/well, mean +/- SD), production of prostacyclin in vitro was significantly inhibited by acetaminophen at 10 micrograms/ml (321 +/- 25) and 100 micrograms/ml (257 +/- 14). This inhibition is similar to inhibition by 10 micrograms/ml of indomethacin (228 +/- 11). Excretion of prostacyclin metabolite was significantly lower after ingestion of acetaminophen (2233 +/- 446 vs 1246 +/- 199 pg/mg creatinine, mean +/- SEM) but unchanged after ingestion of placebo (1745 +/- 304 vs 1712 +/- 211). There was no difference in response between normal and hypertensive women, and there was no effect of acetaminophen on thromboxane metabolite excretion. CONCLUSION: Acetaminophen in typical oral doses results in reduced production of prostacyclin by endothelial cells in culture and in a reduction in prostacyclin, but not thromboxane, production in pregnant women. PMID- 8475963 TI - Alterations in vitamin D and calcium metabolism with magnesium sulfate treatment of preeclampsia. AB - OBJECTIVE: Our purpose was to determine the effects of magnesium sulfate therapy on preeclamptic women and their fetuses with regard to the hormones and ions involved with calcium homeostasis, including 1,25-dihydroxyvitamin D, 25 hydroxyvitamin D, parathyroid hormone, and calcium. STUDY DESIGN: The study group comprised 15 preeclamptic women at term treated with magnesium sulfate during labor. Controls were seven normal women in term labor. The hormones and ions were measured in maternal blood obtained at the onset of labor and at delivery and in umbilical venous (fetal) blood. RESULTS: Baseline maternal levels of 25 hydroxyvitamin D and parathyroid hormone were lower in preeclamptics than in controls. Magnesium infusion led to significant elevations in magnesium, 1,25 dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone levels and lowered calcium concentrations. Fetuses of treated subjects demonstrated reductions in serum total and ionized calcium and elevations of 1,25 dihydroxyvitamin D and parathyroid hormone. CONCLUSION: Magnesium sulfate infusion causes reductions in both maternal and fetal calcium levels. Both mother and fetus respond with increased 1,25-dihydroxyvitamin D and parathyroid hormone levels, which may prevent more severe maternal, fetal, and neonatal hypocalcemia. PMID- 8475964 TI - Transitional cell carcinoma of the ovary: a matched control study of advanced stage patients treated with cisplatin-based chemotherapy. AB - OBJECTIVE: The purpose of this study was to compare patients with advanced-stage transitional cell carcinoma of the ovary with those who had poorly differentiated serous carcinoma for surgical response and survival. STUDY DESIGN: Sixty-two patients with transitional cell carcinoma were identified through a retrospective review and were matched with serous carcinoma patients for stage and residual disease. All patients received cisplatin-based chemotherapy. End points selected for analysis were surgical response, progression-free survival time, and survival time. Univariate and multivariate regression analyses were also performed. RESULTS: The surgical complete response rate for patients with transitional cell carcinoma was 37%, compared with 11% for those with serous carcinoma (p < 0.001). The survival time was significantly longer for the patients with transitional cell carcinoma (median 52.3 vs 22.0 months) (p < 0.001). Multivariate analyses strengthened these findings. CONCLUSION: Transitional cell carcinoma of the ovary is significantly more chemosensitive and associated with a better prognosis than the more common serous carcinoma. PMID- 8475965 TI - Estrogen and interrupted progestin: a new concept for menopausal hormone replacement therapy. AB - OBJECTIVE: We tested a new hormone replacement formulation based on the hypothesis that interrupted administration of progestin in the presence of continuous estrogen would result in receptor up-regulation and resensitization of target tissues to both estrogen and progestin. As a result, symptom control might be possible with lower doses of steroids and in the absence of withdrawal bleeding. STUDY DESIGN: Forty postmenopausal women were entered in a 6-month pilot study, including an 18-month extension. They received piperazine estrone sulfate 0.75 mg daily. Norethindrone 0.35 mg daily was added in 3-day phases, alternating with progestin-free phases of 3 days. There was no steroid-free withdrawal period. We examined symptom control, bleeding patterns, endometrial protection, and lipid profiles in the women over the 24 months of the study. RESULTS: Hot flushes were completely eliminated in 76% of women, and 80% had no bleeding by 6 months. There were three dropouts. Thirty-three women elected to continue after the first 6 months and completed 24 months on therapy for a compliance rate of 82.5%. No endometrial hyperplasia was seen on serial biopsies, and no changes occurred in lipids except for a small but statistically significant decrease in high-density lipoproteins and triglycerides at 24 months. CONCLUSION: Our preliminary results of low bleeding rates, good symptom control, and endometrial protection suggest that hormone replacement with low-dose estrogen and interrupted progestin is effective and may lead to improved compliance in menopausal women. PMID- 8475966 TI - Maternal risk factors and their influence on fetal anthropometric measurements. AB - OBJECTIVE: Our purpose was to determine if and when maternal risk factors and fetal sex have an impact on specific fetal anthropometric measurements assessed by ultrasonography. STUDY DESIGN: Serial ultrasonographic examinations were performed on 1205 fetuses of indigent multiparous women who ultimately gave birth at term. Femur length, abdominal circumference, and head circumference measurements were obtained at mean gestational ages of 18, 25, 31, and 36 weeks, and an estimated fetal weight was calculated. At birth the infant was weighted and head circumference, abdominal circumference, femur length, and crown-heel length measurements were made. Regression analyses were used to determine the effect on each measurement of maternal race, height, body mass index, hypertension, weight gain, smoking, previous low birth weight, and fetal sex. RESULTS: Acting through their effect on head circumference, abdominal circumference, and fetal length, each of the risk factors and female sex were shown to have a negative effect on fetal weight. The timing of the impact, its magnitude, and the specific anthropometric measurement affected were different for each of the risk factors. CONCLUSIONS: The impact of maternal risk factors and fetal sex on estimated fetal weight has been demonstrated to occur first in specific gestational age windows and is mediated through effects on specific fetal anthropometric measurements. PMID- 8475967 TI - Deoxyribonucleic acid analysis facilitates the pretreatment identification of high-risk endometrial cancer patients. AB - OBJECTIVE: Our purpose was to assess the proficiency with which cytometrically determined deoxyribonucleic acid variables from pretreatment curettage specimens identify patients at high risk for extrauterine disease or posttreatment relapse. STUDY DESIGN: Flow cytometrically determined deoxyribonucleic acid ploidy, S phase fraction, deoxyribonucleic acid index, and proliferative index were assessed in 140 paraffin-embedded curettage specimens containing endometrial carcinoma. RESULTS: Although clinical staging identified only 19% of patients with advanced disease, 46% of surgical stages III and IV were aneuploid, 69% had an S-phase fraction > or = 9%, and 69% had a proliferative index > or = 14%. Documented recurrences and cancer-related deaths correlated with nondiploid patterns (29% of 140, 50% of recurrences, 54% of deaths), S-phase fraction > or = 9% (41% of 140, 67% of recurrences, 75% of deaths), and proliferative index > or = 14% (45% of 140, 73% of recurrences, 79% of deaths). Deoxyribonucleic acid index (< 1.5 vs > 1.5) provided additional stratification of aneuploid tumors (p < 0.01). Multivariate analysis identified the proliferative index as the most cogent independent prognostic factor (p < 0.01). CONCLUSION: Deoxyribonucleic acid ploidy and proliferative activity in pretreatment curettage specimens identified the majority of patients at high risk for extrauterine metastasis and relapses. PMID- 8475968 TI - Affinity labeling identifies histidine at the active site of human placental 3 beta-hydroxysteroid dehydrogenase and steroid 5-->4-ene-isomerase. AB - OBJECTIVE: Our aim was to determine if the multifunction enzyme, 3 beta hydroxysteroid dehydrogenase and steroid 5-->4-ene-isomerase has one or more active sites to effect dehydrogenase and isomerase activities. STUDY DESIGN: This steroid, which we have purified to homogeneity from human placental microsomes, was inactivated by the affinity labeling steroid, 2 alpha-bromo[2' 14C]acetoxyprogesterone. The amino acids that were radioalkylated in the absence and presence of the dehydrogenase substrate pregnenolone were identified. RESULTS: Pregnenolone completely abolished the inactivation of dehydrogenase. Histidine was localized in the active site of 3 beta-hydroxysteroid dehydrogenase because the radiolabel disappeared from enzyme inactivated in the presence of pregnenolone. Cysteine, a major radiolabeled product (80%) in the absence of pregnenolone, was decreased twofold in incubations that contained pregnenolone. Neither pregnenolone nor the isomerase substrate 5-androstene-3,17-dione protected isomerase from inactivation by the affinity alkylator. CONCLUSION: This observation contradicts coexisting, separate binding sites, one for each activity. Rather, a conformation shift around one binding region prompted by products of the dehydrogenase reaction may create the isomerase activity. PMID- 8475969 TI - Preterm birth prevention: where are we? AB - OBJECTIVE: The purpose of this study was to review the current approaches to preventing preterm delivery. STUDY DESIGN: The problem of preterm birth was assessed by reviewing the different components that play a role in preterm birth prevention, excluding infection, antibiotic treatment, and tocolytic treatment. RESULTS: Prevention of preterm labor must initially discriminate those at risk. Positive predictive values of various approaches are currently not adequate enough to warrant intervention. Prevention modalities, in part because of poor prediction, are mostly unproved. Accurate diagnoses of preterm labor remains difficult and confuses analyses of tocolytic agents. Cervicovaginal fetal fibronectin, perhaps in combination with cervical evaluation, shows promise. Early detection programs remain controversial, but most reviews indicate that daily patient contact with high-risk patients gives cause for some optimism. Antenatal maternal glucocorticoid treatment at specific gestational ages improves neonatal outcome. CONCLUSION: The incidence of preterm birth is rising in the country. However, improved definition of the various components of the problem has provided an improved understanding of the problem. There is a new continuing effort and a search for new and innovative ways to address this vexing national problem. PMID- 8475970 TI - Are physical activity and employment related to preterm birth and low birth weight? AB - OBJECTIVE: The purpose of this study was to review the validity of published studies that consider modifying physical activity during pregnancy to decrease preterm births and low birth weight. STUDY DESIGN: Presented is a critical review of extant literature, both case-control studies and studies of pregnant women followed up in cohort fashion. RESULTS: Studies both showing and not showing an association between employment and adverse outcome exist. However, no randomized trials have been reported. The most plausible associations exist for prolonged standing, long working hours, and lifting heavy objects. CONCLUSION: Until the biologic basis of parturition is known, definitive conclusions are probably not possible. Proposals to require pregnancy leave for all employees seem premature. However, physicians must be sensitive to dilemmas faced by some employees and encourage voluntary leave for those placed in positions characterized by occupational fatigue. PMID- 8475971 TI - Antibiotics in the treatment of preterm labor. AB - OBJECTIVE: Clinical evidence for a relationship between chorioamnionitis and the onset of preterm labor, supported by well developed biochemical models of that interaction, motivated a review of prospective, randomized trials of antibiotic use in its prevention. STUDY DESIGN: A literature search was made of antibiotic trials applied to women at risk for preterm labor and with a clinical diagnosis of preterm labor after premature preterm rupture of membranes. A review of two retrospective case-control studies conducted on pregnant women with positive cultures for Chlamydia trachomatis is also included. RESULTS AND CONCLUSION: Results of antibiotic use in women with preterm premature rupture of membranes supports significant prolongation of the interval from rupture of membranes to delivery and improvement and neonatal outcome in treated patients. PMID- 8475972 TI - Low target birth weight or growth retardation? Umbilical Doppler flow velocity waveforms and histometric analysis of fetoplacental vascular tree. AB - OBJECTIVE: The placental vascular architecture of small-for-gestational-age fetuses seems to have an impact on the flow patterns in the umbilical arteries. STUDY DESIGN: Blood flow velocity waveforms of the umbilical arteries were measured by Doppler ultrasonography in nine small-for-gestational-age fetuses with elevated systolic/diastolic ratios of the umbilical arteries, seven small for-gestational-age fetuses with normal flow patterns, and 14 appropriate-for gestational-age fetuses with normal flow patterns. After delivery histomorphometric placental investigations were performed. RESULTS: Reduced end diastolic flow velocities were significantly associated with both a reduction of vascularization within the terminal villi and adverse diffusion conditions, indicating insufficient functional maturity. The perfusion and diffusion capacity of small-for-gestational-age placentas with normal umbilical artery flow velocity waveforms was similar or even slightly better compared with the appropriate-for gestational-age control values. CONCLUSION: These data suggest that Doppler flow velocimetry in the umbilical arteries is predictive of a vascular lesion within the placentas of small-for-gestational-age fetuses. PMID- 8475973 TI - Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin. AB - OBJECTIVE: To study the effect of long-term treatment during gestation with heparin on the incidence of osteoporotic fractures and thromboembolic recurrence. STUDY DESIGN: Long-term subcutaneous prophylaxis with heparin twice daily in pregnancy was prescribed for 184 women, during a decade because of an increased risk of thromboembolism. The dosage of heparin was adjusted to anti-factor Xa activity or activated partial thromboplastin time and different regimens were given, depending on the risk of recurrence. RESULTS: For the total group the mean dosage of heparin ranged from 13,000 to 40,000 IU per 24 hours (mean 19,100 IU per 24 hours), and the average duration of treatment was 25 weeks. Symptomatic osteoporotic fractures of the spine occurred post partum in four women, for whom the mean dosage of heparin ranged from 15,000 to 30,000 IU per 24 hours (mean 24,500 IU per 24 hours), and the duration of treatment ranged from 7 to 27 weeks (mean 17 weeks). In spite of prophylaxis with heparin, thromboembolic complications occurred in five women. They had either nonsatisfactory concentrations of heparin according to our regimen or were later diagnosed as having a coagulation disorder known to increase the risk of thromboembolism. CONCLUSION: Osteoporotic vertebral fractures were found in 2.2% of the women, and a relationship to the amount of heparin was indicated, although fractures were not avoided during low-dose, short-term prophylaxis. Recurrence of thromboembolism occurred in 2.7% of the patients, but if a strict heparin adjustment had been performed, recurrence could probably have been prevented. PMID- 8475974 TI - Relationship of circadian rhythms of uterine activity with term and preterm delivery. AB - OBJECTIVE: Our aim was to document the presence or significance of circadian uterine activity rhythms in pregnant women who delivered at term and preterm. STUDY DESIGN: We measured uterine activity in 19 women divided into a control group (low risk for preterm labor, term delivery, n = 7), a group at high risk for preterm labor, term delivery (n = 6), and a group at high risk for preterm labor, preterm delivery (n = 6). Patients were hospitalized for 24 hours every 2 weeks from 26 weeks' gestation until delivery. Uterine activity was measured continuously by external tocodynamometer. RESULTS: Patients delivering at term demonstrated a nocturnal surge (4 to 7 AM) in uterine activity the last 80 days before delivery (p < 0.05, analysis of variance). Patients delivered preterm showed an initial nocturnal surge of uterine activity similar to those delivered at term, but this disappeared 24 days before delivery (p > 0.05, analysis of variance). CONCLUSION: Uterine activity nocturnal surges normally precede term delivery. These surges are lost in women who deliver prematurely. PMID- 8475975 TI - Effect of intravenous beta-sympathomimetic tocolysis on human fetal serum erythropoietin levels. AB - OBJECTIVE: The major stimulus for erythropoietin production is tissue hypoxia. We sought to investigate the relationship of beta-sympathomimetic administration for tocolysis and fetal serum erythropoietin. STUDY DESIGN: Umbilical cord blood was obtained from infants whose mothers received intravenous beta-sympathomimetic tocolysis and who were delivered at < or = 34 weeks' gestation. Serum erythropoietin was measured by radioimmunoassay. On the basis of the presumed 2- to 4-hour half-life of fetal erythropoietin, the infants were divided into two groups. In group 1 (n = 16) beta-sympathomimetic therapy was discontinued < 24 hours before delivery; in group 2 (n = 11) it was discontinued > or = 24 hours before delivery. RESULTS: Group 1 fetuses had significantly higher erythropoietin levels than did group 2 fetuses (37.3 vs 13.9 mU/ml, p = 0.02). The duration of beta-sympathomimetic tocolysis and the maximum infusion rate were not different. The two groups did not differ in gestational age, birth weight, route of delivery, presence of labor, or duration of first or second stage of labor. CONCLUSIONS: We speculate that intravenous beta-sympathomimetic tocolytic therapy stimulates fetal erythropoietin production by decreasing fetal oxygenation as a result of the reversible fetal metabolic effects of the tocolysis. These data suggest that beta-sympathomimetic tocolysis should be undertaken cautiously if fetal compromise is suspected, fetal well-being should be assessed carefully if tocolysis is undertaken, and treatment should be discontinued promptly if a clear benefit is not realized. PMID- 8475976 TI - Massive hydronephrosis mimicking theca lutein cysts in association with partial hydatidiform mole. AB - We present an unusual case of partial hydatidiform mole in which extensive, multiple cystic structures encompassing the entire right abdomen and pelvis, initially thought to represent theca lutein cysts, were subsequently shown to consist of massive unilateral right hydronephrosis. Percutaneous nephrostomy decompression bypassing the ureteropelvic obstruction revealed functional renal parenchyma. PMID- 8475977 TI - Malignant ventricular arrhythmias in eclampsia: a comparison of labetalol with dihydralazine. AB - OBJECTIVE: Our aim was to assess the impact of beta-adrenergic blockade during the peripartum period on the previously observed high incidence of ventricular arrhythmias in eclamptic parturients. STUDY DESIGN: An open, randomized comparison of intravenous labetalol versus dihydralazine was conducted in 40 eclamptic subjects in the peripartum period. Cardiac rhythm was assessed by blinded analysis of a 24-hour Holter record by means of the Lown classification of arrhythmias. RESULTS: There was a significantly higher incidence of serious ventricular arrhythmias in patients receiving dihydralazine (81%) than in those receiving labetalol (17%, p < 0.0001). Patients receiving labetalol showed a significant decrease in mean heart rate (p < 0.0001), whereas patients receiving dihydralazine showed a significant increase (p < 0.0001). CONCLUSION: The introduction of beta-adrenergic blockade into peripartum hypertensive management of eclampsia significantly reduced the incidence of dangerous ventricular arrhythmias. Myocardial oxygen supply/demand ratio may be improved by beta blockade. PMID- 8475978 TI - Trends in cesarean section use in California, 1983 to 1990. AB - OBJECTIVE: Our aim was to assess recent trends in cesarean section use in California. STUDY DESIGN: California discharge abstract data on hospital deliveries in 1983 through 1990 (379,759 to 587,508 annual deliveries) were used to analyze time trends by indication, age, race, and payment source. RESULTS: California cesarean section rates increased annually from 21.8% in 1983 to 25.0% in 1987 and then decreased to 22.7% by 1990. Similar patterns were noted for all age and race or ethnicity groups. Primary cesarean section rates increased from 15.2% in 1983 to 17.9% in 1987, then decreased to 16.2% by 1990. Declines in repeat cesarean section rates continued throughout 1983 through 1990, accelerating after 1987. For both primary and repeat cesarean section rates, time trends after mid-1987 were significantly different than those for 1983 to 1987. CONCLUSION: After increasing from 1983 to 1987, California cesarean section rates declined from 1988 to 1990. Existing payment source differences in cesarean section use increased in magnitude from 1983 to 1990, with privately insured women consistently having the highest cesarean section rates. PMID- 8475979 TI - Effect of early pregnancy on maternal regional cerebral blood flow. AB - OBJECTIVE: The purpose of this study was to assess the effect of early pregnancy on maternal regional cerebral blood flow. STUDY DESIGN: We studied 10 pregnant women at 7 to 19 weeks' gestation by the xenon 133 washout technique by means of single-photon emission computed tomography the day before the abortion was induced and then again at a mean of 42.8 days after the abortion. RESULTS: Blood flow in the cerebral hemispheres decreased after the abortion, with a decline of 8.1% (p < 0.001). Each regional decrease was as follows: 7.6% (p < 0.01) in the frontal lobe, 9.1% (p < 0.01) in the temporal lobe, 12.9% (p < 0.001) in the parietal lobe, 9.8% (p < 0.01) in the basal ganglia, and 16.7% (p < 0.001) in the cerebellum. There was no significant difference in blood flow in the occipital lobe before versus after the abortion. CONCLUSION: Maternal regional cerebral blood flow was increased in early pregnancy compared with the nonpregnant state, except in the occipital lobe. PMID- 8475980 TI - Intraobserver and interobserver variability of the amniotic fluid index. AB - OBJECTIVE: We assessed intraobserver and interobserver variations in the performance of the amniotic fluid index. STUDY DESIGN: A total of 34 women in the third trimester with intact membranes were examined twice by each of three examiners. The amniotic fluid index was measured once by each of the three examiners in order, then repeated by each examiner in the same order. Numeric displays on the video terminal screen were covered so that the examiners were blinded to actual measurement values. Results were recorded on hard copy for later data analysis. A senior investigator supervised all examinations to monitor consistency of technique. RESULTS: Overall, the coefficient of variation for amniotic fluid index measurements varied from 10.8% within examiners to 15.4% between examiners. Both between and within variation of absolute differences increased as the amniotic fluid index value increased, while the percent difference decreased. Simply repeating the test by the same examiner will decrease the coefficient of variation significantly. CONCLUSION: Although intraobserver and interobserver variability cannot be eliminated, its impact can be minimized by use of the same examiner for serial studies. PMID- 8475981 TI - Platelet-activating factor treatment of human spermatozoa enhances fertilization potential. AB - OBJECTIVE: The purpose of this study was to evaluate the effects of platelet activating factor treatment on human spermatozoa fertilizing capability, as assessed by the zona-free hamster penetration assay. STUDY DESIGN: Twenty-three semen specimens were divided into two groups on the basis of initial motile sperm count greater or less than 20 x 10(6)/ml. Each sample served as its own treatment control. Twice-washed spermatozoa were treated with 1 x 10(-7) mol/L of platelet activating factor before performing the sperm penetration assay. For the two groups the percent penetrations and penetration index were compared with the paired t test, and an independent t test was used to compare parameters between groups. RESULTS: Significant enhancement of both percent penetrations (p < 0.0001) and penetration index (p < 0.005) were noted on platelet-activating factor treatment in both groups. Enhancement of both indices were noted to be independent of initial motile sperm counts. CONCLUSION: Platelet-activating factor treatment of human spermatozoa may be of potential therapeutic value in certain cases of asthenospermia or fertilization failure in human in vitro fertilization. PMID- 8475982 TI - Transforming growth factor-beta 2 prevents preterm delivery induced by interleukin-1 alpha and tumor necrosis factor-alpha in the rabbit. AB - OBJECTIVES: The purpose of the study was to determine whether preterm parturition in the rabbit can be induced by intraamniotic injection of proinflammatory cytokines, interleukin-1 alpha and tumor necrosis factor-alpha, and whether transforming growth factor-beta 2, an inhibitor of the cytokine-induced prostaglandin synthesis, modifies the effect of these cytokines. STUDY DESIGN: New Zealand White rabbits were injected in each amniotic cavity on day 24 of gestation with one of the following: a combination of interleukin-1 alpha (150 ng) and tumor necrosis factor-alpha (1.25 micrograms), 50 ng of transforming growth factor-beta 2 concomitantly with interleukin-1 alpha and tumor necrosis factor-alpha, or vehicle. In the first study the animals were observed for signs of delivery until day 29 of gestation. In the second study the effect of transforming growth factor-beta 2 (50 ng/fetus) on the rate of premature delivery was evaluated. In the third study the concentrations of prostaglandin E2 and 13,14-dihydro-15-keto-prostaglandin F2 alpha were measured in the amniotic fluid on day 27 of gestation. The statistics used were Fisher's exact test, the chi 2 test, and the Mann-Whitney U test. RESULTS: Altogether 61 of 191 fetuses (32%) were born prematurely in the interleukin-1 alpha-tumor necrosis factor-alpha group, whereas only two of 161 fetuses (1.2%) (p = 0.0001) and one of 159 (0.6%) (p = 0.0001) were born prematurely in the interleukin-1 alpha-tumor necrosis factor-alpha-transforming growth factor-beta 2 group and in the control group, respectively. Of the 23 animals injected with interleukin-1 alpha and tumor necrosis factor-alpha, six (26%) delivered all of their fetuses prematurely versus none in the other groups (p = 0.02). None of the 88 fetuses in the transforming growth factor-beta 2 group were born prematurely. The prostaglandin E2 concentrations in the amniotic fluids were higher in the interleukin-1 alpha tumor necrosis factor-alpha group than in the interleukin-1 alpha-tumor necrosis factor-alpha-transforming growth factor-beta 2 group (p = 0.05) or in the control group (p = 0.02). CONCLUSIONS: Preterm parturition can be provoked in the rabbit by intraamniotic injections of interleukin-1 alpha and tumor necrosis factor alpha. Transforming growth factor-beta 2 prevents the cytokine-induced increase in premature delivery. PMID- 8475983 TI - Histocompatibility antigens and pregnancy outcome. PMID- 8475984 TI - Severe pregnancy-induced hypertension and blood pressure control during general anesthesia: nitroglycerin or opioids, the logical choice? PMID- 8475985 TI - Laparoscopic surgery: experiment or expedient? PMID- 8475986 TI - Colposcopy and rape. PMID- 8475987 TI - Middle cerebral artery flow velocity waveforms and fetal compromise. PMID- 8475988 TI - Hyperbaric oxygenation for necrotizing fasciitis. PMID- 8475989 TI - Psychological sequelae of childhood sexual abuse: relevant in subsequent pregnancy. PMID- 8475990 TI - CD44 and hyaluronan expression in human cutaneous scar fibroblasts. AB - Fibrotic disorders of skin and other organs are typically associated with an abnormal accumulation of extracellular matrix. This study focuses on a matrix constituent, hyaluronan-which is known to be altered in fibrotic disorders of skin- and on CD44, a cell adhesion molecule and putative receptor for hyaluronan. Tissue samples were obtained from biopsies of human normal skin, normal cutaneous scar; and hypertrophic cutaneous scar. After culturing, cells were studied by single- and double-labeling immunohistochemistry using the two anti-CD44 monoclonal antibodies, BU-52 and J173, and a biotinylated hyaluronan binding complex probe, b-HABR. Certain cultures were pretreated with Streptomyces hyaluronidase to assess the dependency of CD44 expression on the presence of endogenous hyaluronan. CD44 expression, both in the presence and the absence of exogenous hyaluronan, was quantitated by radioimmunobinding assay. Overall glycosaminoglycan synthesis and identification of hyaluronan were accomplished by precursor incorporation assays and by quantitative cellulose acetate electrophoresis. CD44 was found to be a normal human adult fibroblastic antigen whose expression is markedly increased for hypertrophic scar fibroblasts compared with normal skin fibroblasts. Although hyaluronan was found to be the predominant glycosaminoglycan constituent of the pericellular matrix for these fibroblasts, CD44 attachment to the cell surface is neither mediated by hyaluronan nor is the presence of hyaluronan a prerequisite for CD44 expression. Exogenous hyaluronan induced a decline in measurable CD44 expression for normal skin fibroblasts but not for hypertrophic scar fibroblasts. These observations are compatible with current understanding of the way cells manage the hyaluronan economy of the extracellular matrix and emphasize phenotypic heterogeneities between fibroblasts derived from normal versus scar tissues. PMID- 8475991 TI - A 34-kd protein with strong homology to ras-like proteins inhibits epidermal growth factor activity. AB - Epidermal growth factor (EGF) and its analog, transforming growth factor-alpha, are felt to be important in oncogenesis. When malignant rabbit fibroma virus infects RK-13 rabbit kidney cells, a 34-kd protein that inhibits the effects of EGF on certain target cell lines is produced. We have purified this protein using high-pressure liquid chromatography and gel electrophoresis. This purified protein abolishes EGF-induced cellular proliferation. It also causes the EGF receptor-bearing A431 carcinoma cell line to stop proliferating in vitro. This purified 34-kd EGF inhibitor (EGFI) redirects cellular protein phosphorylation in the presence or absence of EGF. Whereas EGF increases phosphorylation of cellular proteins in normal rat kidney cells, clone 49F, and A431 EGFI generally decreases it. Both EGF and EGFI cause increased protein production in A431 and normal rat kidney cells. The major species of protein synthesized by cells seem invariant to EGFI, with or without EGF. The partial protein sequence of two fragments of EGFI shows striking similarity to two ras like proteins. Possible means by which such a ras-like protein might inhibit EGF-induced cellular proliferation are discussed. Therefore, a purified 34-kd ras-like protein inhibits EGF-induced cellular proliferation and changes the targets for cellular protein phosphorylation. Studies are in progress to characterize this protein further, both structurally and functionally. PMID- 8475992 TI - Neoplasia of the ampulla of Vater. Ki-ras and p53 mutations. AB - Eleven tumors of the ampulla of Vater (5 stage IV and 2 stage II adenocarcinomas, 1 stage II papillary carcinoma, 1 neuroendocrine carcinoma, and 2 adenomas, one with foci of carcinoma) were examined for Ki-ras and p53 gene mutations by single strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA fragments. Ki-ras mutations were found in one adenocarcinoma and in the adenoma with foci of carcinoma, both involving mainly the intraduodenal bile duct component of the ampulla. Seven cases showed p53 gene mutations: four advanced-stage adenocarcinomas, the papillary carcinoma, the neuroendocrine carcinoma, and the adenoma with foci of carcinoma. Nuclear accumulation of p53 protein was immunohistochemically detected in the morphologically high-grade areas of the five cancers harboring a p53 gene missense point mutation. The adenomas, the two frame shift-mutated cancers, and the adenomatous and low-grade cancer areas of mutated carcinomas were immunohistochemically negative. Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla. PMID- 8475993 TI - Multiple tumor types appear in a transgenic mouse with the ras oncogene. AB - A transgenic mouse strain with the zeta-globin promoter and the vHa-ras oncogene develops an array of mesenchymal and epithelial neoplasms described here. The predominate mesenchymal tumors were dermal spindle cell tumors, which resembled malignant fibrous histiocytomas found in humans. They were associated with hepatosplenomegaly and developed beneath squamous papillomas. The hepatosplenomegaly was associated with infiltrates of cells that tended toward myelocytic or monocytic differentiation. Other epithelial tumors included keratoacanthomas and squamous cell carcinomas. Squamous cysts, some with squamous cell carcinomas, of the salivary glands and mammary carcinomas were also found. Odontogenic tumors, which sometimes differentiated into ameloblastomas, were one of the more unusual tumor types observed. Other, less frequent tumors were also noted. The tumors described here are a potentially valuable experimental resource that may lead to an understanding of malignant fibrous histiocytoma-like lesions, odontogenic tumors, and tumor progression. PMID- 8475994 TI - Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung. AB - The relationship of asbestos deposition in the lung to subsequent cell proliferation at the pleural surface is not clear. The present study examines DNA synthesis by various pulmonary cells, particularly those at the pleura after intratracheal injection of 0.1 mg crocidolite to mice using: 1) long fibers (> 20 mu), which are deposited in bronchiolar regions and induce fibrosis; 2) short fibers (< 1 mu), which reach alveoli but do not induce fibrosis. Mice also received 2 microCi/g tritiated thymidine 1 hour before death at intervals to 16 weeks. Short fibers induced only a small increase in labeling of bronchiolar epithelial and interstitial cells, which subsided by 5 days, when a small increase in labeled mesothelial and subpleural cells was seen. In contrast, long fibers damaged the bronchiolar epithelium and became incorporated into connective tissue. During regeneration, 12% of cells were labeled at 3 days and labeling was greater than controls to 4 weeks. Increased peribronchiolar labeling of fibroblasts and interstitial macrophages was seen around long fibers, and increased DNA synthesis by mesothelial and subpleural cells was found. Up to 2% of mesothelial cells were labeled 1 week after long fibers compared to near zero in controls. No long fibers were found at the pleura. Activation of interstitial macrophages in response to long crocidolite fibers is associated with fibroblast proliferation. It is now suggested that mesothelial cells may also be stimulated by cytokines from activated interstitial macrophages that diffuse across the interstitium, without requiring actual fiber translocation to the pleura. PMID- 8475995 TI - Suppression of local and systemic responses in streptococcal cell wall-induced acute inflammation of the air pouch by cyclosporine A. Comparison with the effects of two anti-inflammatory bis-benzimidazoles. AB - Injection of streptococcus group A cell wall-derived peptidoglycan polysaccharide into a subcutaneous air pouch causes local outpouring of neutrophils and macrophages and distant hemopoietic proliferation in spleen and bone marrow. Cyclosporine A (CyA) suppressed neutrophil accumulation and all cell lines of hemopoiesis. trans-1,2-Bis(5-amidino-2-benzimidazolyl)ethene (BBE) also interfered with neutrophil exudation, yet reduced only the erythroid component of the hemopoietic process. The ethane analogue of BBE, on the other hand, did not prevent neutrophil emigration, but held down splenic erythropoiesis and myelopoiesis. All three compounds stimulated streptococcus group A cell wall derived peptidoglycan polysaccharide uptake by pouch macrophages. CyA being the least active, BBE and its ethane analogue also produced a shift of wear-and-tear pigment from large numbers of small splenic macro-phages into small numbers of large macrophages. The pouch model is very useful in the study of anti inflammatory compounds and has furnished the first evidence of CyA interference with massive neutrophilic infiltration and with hemopoietic signals. PMID- 8475996 TI - Gingival mononuclear cells from chronic inflammatory periodontal tissues produce interleukin (IL)-5 and IL-6 but not IL-2 and IL-4. AB - A unique characteristic of the localized inflammatory tissue in the periodontium (e.g., adult periodontitis [AP]) is the accumulation of IgG (IgG1 > IgG2 > IgG3 > or = IgG4) followed by IgA plasma cells (IgA1 > IgA2). However, the exact molecular mechanisms contributing to these elevated B-cell responses at the local disease site are still unknown. Thus, this study has examined the production of cytokines of importance in B-cell responses, e.g., interleukin (IL)-2, IL-4, IL 5, and IL-6 by gingival mononuclear cells (GMC) isolated from patients in severe stages of AP. These cytokines were assessed at the protein and messenger (m)RNA levels to understand their importance for the observed increased B-cell responses present in these tissues. Among the four cytokines tested by respective cytokine specific, polymerase chain reaction and dot-blot hybridization, high levels of IL 5- and IL-6-specific mRNA were noted in GMC freshly isolated from AP patients. On the other hand, specific message for IL-2 and IL-4 were not present. Further, the analysis of culture supernatants of GMC also revealed that cells from AP patients spontaneously produced IL-5 and IL-6 but not IL-2 and IL-4. In contrast, when peripheral blood mononuclear cells isolated from the same patients were examined for these cytokines, no detectable levels of mRNA or secreted cytokines were noted. These results showed that GMC from localized inflammatory tissues in severe stages of AP possess a distinct cytokine profile represented by high levels of IL-5 and IL-6 mRNA expression and protein synthesis, whereas IL-2 and IL-4 were not detected. Further, this study supports the concept that AP is a localized inflammatory disease, because GMC from the inflamed tissue actively produce IL-5 and IL-6, whereas peripheral blood mononuclear cells from the same patients do not. PMID- 8475997 TI - Effects of interferon-gamma on primary cultures of human brain microvessel endothelial cells. AB - Primary cultures of human brain microvessel endothelial cells were used to study the effects of human recombinant interferon-gamma (IFN-gamma) on cerebral endothelium in vitro. Incubation of monolayers with various concentrations of IFN gamma (10 to 200 U/ml) for 12 to 96 hours induced surface expression of class II major histocompatibility complex (Ia) antigen in a time- and concentration dependent manner. In immunogold-stained cultures, labeling was observed as early as 12 hours, was maximal after 48 hours, and persisted at plateau levels in the continuous presence of the cytokine. Expression was blocked by coincubation with anti-IFN-gamma antibody and was reversed 4 days following removal of IFN-gamma from the culture media. Endothelial cells treated with IFN-gamma for 3 to 4 days became spindle-shaped, extensively overlapped, and frequently formed cellular whorls. These changes did not occur in the presence of anti-IFN-gamma antibody and reversed upon removal of IFN-gamma from the media. The morphological alterations were associated with increased permeability of confluent monolayers to macromolecules as compared with untreated cultures. The results of these studies indicate that human brain microvessel endothelial cells respond to in vitro cytokine stimulation by undergoing profound morphological, functional, and permeability changes. We conclude that cerebral endothelium may play an important role in the initiation and regulation of lymphocyte traffic across the blood brain barrier in inflammatory disorders of the human central nervous system. PMID- 8475998 TI - Reversibility of mild to moderate ischemic injuries in the isolated rat heart. A characterization by 31P-NMR and by physiological and ultrastructural indices. AB - We have studied cardiac function, metabolism, and ultrastructure during reperfusion after global ischemia of short duration (6 and 12 minutes) in isolated rat hearts. Our aim was to obtain more detailed information on the reversibility of changes following presumedly mild and moderate ischemic injuries by use of multiple time-based indices. In a modified Langendorff perfusion system, hearts were subjected to 24 minutes of control perfusion and 6 or 12 minutes of ischemia followed by 1.5 or 24 minutes of reperfusion. During the experiments we monitored left ventricular developed pressure (LVDP), heart rate, and coronary flow rate, and intracellular phosphocreatine (PCr), inorganic phosphate (P(i)), pH, and ATP by 31P nuclear magnetic resonance spectroscopy. The number of cells with sarcolemmal and nuclear injuries was counted. Our main findings during 24 minutes of reperfusion following 6 and 12 minutes of ischemia were 80% versus 53% recovery of LVDP at the end of reperfusion, an increased PCr, 80% versus 65% recovery of ATP, and a rapid versus slower recovery of pH. Ultrastructural examination revealed sarcolemmal and unclear abnormalities at the end of ischemia, these alterations being fully (rapidly versus more slowly) reversible during reperfusion. According to these findings, there was a dissociation between an essentially normal ultrastructure, and a depressed recovery of LVDP, reduced ATP, and an overshoot of PCr upon 24 minutes of reperfusion after 12 minutes of ischemia. This may indicate a postischemic dysfunction closely related to stunning. PMID- 8475999 TI - Influence of the estrous cycle on the development of upper genital tract pathology as a result of chlamydial infection in the guinea pig model of pelvic inflammatory disease. AB - Guinea pigs were infected intravaginally with the chlamydial agent of guinea pig inclusion conjunctivitis at varying times during the estrous cycle. Genital tract tissues were collected 30 days after infection and processed for histopathological analysis. No difference was seen in the course of lower genital tract infection. However, a significantly greater percentage of tissues from animals infected on day 11 of the cycle were found to have chronic inflammation and fibrosis in the mesosalpinx compared to those from animals infected on day 6 or day 16. In addition, a significantly greater percentage of oviduct tissues from day 11-infected guinea pigs had marked tubal dilatation when compared to oviducts from day 6-or day 16-infected animals. The increased incidence of pathological changes was also noted in the endocervix, uterine fundus, and uterine horns but not the exocervix. These data indicate that the time of the estrous cycle and the corresponding hormonal influences may be an important influence on the development of upper genital tract disease. PMID- 8476000 TI - Pathology and molecular diagnostics: issues of structure and organization. PMID- 8476001 TI - Geographic variation of six dermatoglyphic traits in Eurasia. AB - We describe the geographic variation patterns of six dermatoglyphic traits from 144 samples in Eurasia. The methods of analysis include computation of interpolated surfaces, one-dimensional and directional correlograms, correlations between all pairs of surfaces, and distances between correlograms. There are at least two, probably three, distinct and significant patterns of variation. 1) A general NW-SE trend for pattern intensity, the main line index, and frequency of hypothenar patterns. 2) A trend from the Middle East to the north and east for frequency of axial triradius and of accessory interdigital triradii. 3) A patchy pattern for frequency of the thenar-interdigital 1. The results are compatible with a diffusion process between Europe and the peoples of Northern Asia, and possibly with a radiation of populations from the Middle East. The hypothesis of diffusion processes is supported by substantial interpopulation correlations between dermatoglyphic traits that contrast sharply with largely negligible intralocality correlations. PMID- 8476002 TI - Temporal craniometric changes from the Jomon to the Modern period in western Japan. AB - Temporal changes in morphometric features of human cranial remains from the late Jomon period (1500 B.C.-300 B.C.) to the Modern period (1900-1950 A.D.) in western Japan are examined. The results of univariate and multivariate analysis indicate that the Yayoi people (300 B.C.-300 A.D.), characterized by high faces and tall stature, show morphological discontinuity with the earlier Jomon people, who exhibit lower faces and shorter stature. This discontinuity contrasts with the relatively continuous changes among populations after the Yayoi. Comparing these changes with those documented in the Kanto region of eastern Japan indicates there are significant regional differences in the degree and rate of transformation in certain cranial features, especially facial height, between the two regions. Differences in cranial shape between the two regions become apparent during the Yayoi period and these differences tend to diminish thereafter. The most plausible explanation for these observed changes is the introduction of new genes, coinciding with the arrival of new immigrants from the Asian continent in the northern Kyushu-Yamaguchi region at the beginning of the Yayoi period. Further testing of this hypothesis will be necessary before definitive conclusions can be reached regarding the appearance of modern Japanese. PMID- 8476003 TI - Human dental arch shape evaluated by euclidean-distance matrix analysis. AB - Form differences between biological structures can be evaluated using several approaches. When landmark data are available, a recently proposed method (euclidean-distance matrix analysis) seems to be able to differentiate between size and shape differences. This method also localizes those areas which differ most between the two structures. We have applied it to analyze the sexual dimorphism in dental arch form in a sample of 50 men and 45 women. Subjects ranged in age between 20 and 27 years, and had sound dentitions. Fourteen landmarks, corresponding to the centers of gravity (centroids) of the occlusal surfaces of all permanent teeth (right second molar to left second molar), were individualized on the dental casts of subjects. All the possible linear distances between pairs of teeth were computed, thus creating four mean form matrices (one for each arch within sex). Gender differences were tested by using euclidean distance matrix analysis. No significant differences were demonstrated in the shape of arches, while male arches proved to be slightly bigger than female arches. PMID- 8476004 TI - New method of three-dimensional analysis of bipedal locomotion for the study of displacements of the body and body-parts centers of mass in man and non-human primates: evolutionary framework. AB - The current biomechanical interpretation of the chimpanzee's bipedal walking argues that larger lateral and vertical displacements of the body center of mass occur in the chimpanzee's "side-to-side" gait than in the human striding gait. The evolutionary hypothesis underlying this study is the following: during the evolution of human bipedalism one of the necessary changes could have been the progressive reduction of these displacements of the body center of mass. In order to quantitatively test this hypothesis, it is necessary to obtain simultaneously the trajectories of the centers of mass of the whole body and of the different body parts. To solve this problem, a new method of three-dimensional analysis of walking, associated with a volumetric modelling of the body, has been developed based on finite-element modeling. An orthogonal synchrophotographic device yielding four synchronous pictures of the walking subject allows a qualitative analysis of the photographic sequences together with the results of their quantitative analysis. This method was applied to an adult man, a 3-year-old girl and a 9-year-old male chimpanzee. Our results suggest that the trajectory of the body center of mass of the human is distinguished from that of the chimpanzee not by a lower movement amplitude but by the synchronization of the transverse and vertical displacements into two periodic curves in phase with one another. The non-human primate uses its repertoire of arboreal movements in its bipedal terrestrial gait, provisionally referred to as a "rope-walker" gait. We show that the interpretation of a "side-to-side" gait is not applicable to the chimpanzee. We argue that similarly this interpretation and the initial hypothesis presuppose a basic symmetric structure of the gait, in relation to the sagittal plane of progression, similar to the human one. This lateral symmetry of the right and left displacements of the center of gravity, in phase with the right and left single supports of walking, is probably a very derived feature of the human gait. We suggest that low lateral and vertical displacements of the body center of mass are not indicative of a progressive bipedal gait and we discuss the new evolutionary implications of our results. PMID- 8476005 TI - Brief communication: gut morphology of Callithrix nigriceps and Saguinus labiatus from western Brazilian Amazonia. AB - Quantitative data on the gut proportions of the recently-described black-headed marmoset (Callithrix nigriceps) from western Brazilian Amazonian are presented. Like other marmosets, C. nigriceps exhibits a relatively large caecum and colon associated with adaptations for gummivory. The degree of gut specialisation recorded is greater than that for any other platyrrhine for which quantitative data are available. Gum was found in the stomach contents of all four individuals examined, although the fruit/seeds of as many as seven different plant taxa were also encountered, in addition to insects of six different orders. Gut proportions of two Saguinus labiatus from the same region were typical of the more frugivorous tamarins, and stomach contents included only fruit and insects. Relative gut proportions of both species were closely similar to those of congeners from the same region. PMID- 8476006 TI - Brief communication: measurement size, precision, and reliability in craniofacial anthropometry: bigger is better. AB - In this paper we examine the results of an intraobserver measurement error study involving 49 craniofacial variables that ranged in size from less than 1 cm to approximately 20 cm. Repeat measurements were taken on 10 male and 10 female adult subjects (19-59 years old). Our focus is on the relationship between measurement size and measurement error across the 49 variables. We found that the size of the variable showed no relationship with the magnitude of the error as measured by the technical error of measurement. When the error was expressed as a coefficient of relative variation (Malina et al.: Vital and Health Statistics, Series 11, No. 23. Washington, DC: US Department of Health and Human Services, 1973), this quantity was negatively associated with the size of the measurement. Conversely, reliability (Fleiss: The Design and Analysis of Experiments. New York: John Wiley & Sons, 1986) was positively correlated with measurement size. We did not find effects of scale (Marks et al.: Am. J. Epidemiol. 130:578-587, 1989) within the individual measurements. Thus, for the range of size of the craniofacial measurements in this study, measurement size must be added to the list of factors such as ease of locating landmarks, measurement technique, and systematic bias in the application of the technique that can affect precision and reliability in anthropometry. PMID- 8476007 TI - Squamosal suture of cranium KNM-WT 17000. PMID- 8476008 TI - Functional significance of an ossified mandibular symphysis: a reply. PMID- 8476009 TI - Technical note: on the measurement of direct vs. projected anthropometric lengths. PMID- 8476010 TI - Blockers of voltage-gated K channels inhibit proliferation of cultured brown fat cells. AB - Cultured brown fat cells have both voltage- and Ca(2+)-activated potassium channels. We tested whether potassium channel activity is necessary for brown fat proliferation by growing adipocytes and preadipocytes from neonatal rat brown fat in the presence of potassium channel blockers. Whole cell patch-clamp experiments showed that verapamil, nifedipine, and quinine block the voltage-gated potassium current (IK,V) with micromolar affinity. Ca(2+)-activated currents (IK,NE) could be activated by micromolar intracellular Ca2+ concentrations and were blocked by nanomolar concentrations of apamin. Both IK,V and IK,NE are blocked by millimolar concentrations of tetraethylammonium (TEA). Under standard culture conditions, the number of cells showing the multilocular morphology characteristic of brown fat cells doubled in 3-5 days. Continuous exposure to 100 nM norepinephrine had no effect on this process. Cell proliferation was inhibited by TEA, quinine, or verapamil. The inhibition was dose dependent, with concentrations for half-block of cell proliferation similar to the Kd values for block of IK,V. Apamin, which selectively blocks IK,NE, had no effect on cell growth. These results suggest that functional voltage-gated potassium channels, but not Ca(2+)-activated potassium channels, may be necessary for the normal proliferation of brown fat cells in culture. PMID- 8476011 TI - Unbiased estimates of quantal release parameters and spatial variation in the probability of neurosecretion. AB - A procedure was developed for dealing with two problems that have impeded the use of quantal parameters in studies of transmitter release. The first, involving temporal and spatial biasing in the estimates for the number of functional release sites (n) and probability of release (p), was addressed by reducing temporal variance experimentally and calculating the bias produced by spatial variance in p (var(s)p). The second, involving inaccuracies in the use of nerve evoked endplate potentials (EPPs), was circumvented by using only miniature EPPs (MEPPs). Intracellular recordings were made from isolated frog cutaneous pectoris, after decapitation and pithing of the animals, and the concentration of K+ ([K+]) was raised to 10 mM to increase the level of transmitter release. The number of quanta released (m) by the EPP was replaced by the number of MEPPs in a fixed time interval (bin), and 500 sequential bins used for each quantal estimate. With the use of 50-ms bins, estimates for var(s)p were consistently negative. This was due to too large a bin (and introduction of undetected temporal variance) because the use of smaller bins (5 ms) produced positive estimates of var(s)p. Increases in m, n, and p but not var(s)p were found in response to increases in [K+] or [Ca2+]/[Co2+]. La3+ (20 microM) produced increases in m and n, which peaked after 20 min and declined toward zero. There were also large increases in p and var(s)p, which peaked and declined only to initial control values. The increase in var(s)p was presumed to reflect La(3+) induced release of Ca2+ from intracellular organelles. The results suggest that this approach may be used to obtain unbiased estimates of n and p and that the estimates of var(s)p may be useful for studying Ca2+ release from intraterminal organelles. PMID- 8476012 TI - Stable expression of the cardiac sodium-calcium exchanger in CHO cells. AB - A line of Chinese hamster ovary (CHO) cells called CK1.4 was produced by transfection with the gene for the bovine cardiac Na(+)-Ca2+ exchanger. CK1.4 cells stably expressed substantial exchange activity and exchanger protein as shown by immunoprecipitation. Exchange activity was quantified as 45Ca2+ influx that depended on both increasing intracellular Na+ and lowering the concentration of external Na+. Replacing external Na+ with K+ slightly increased 45Ca2+ uptake by CK1.4 cells with basal Na+ and greatly increased 45Ca2+ uptake by Na(+)-loaded cells. Neither exchange activity nor exchanger protein was detected in the nontransfected parental line. By contrast to CK1.4 cells, replacing external Na+ with K+ decreased 45Ca2+ uptake in the nontransfected cells whether or not they were Na+ loaded. Changes in cytosolic free Ca2+ determined with fura-2 were consistent with the 45Ca2+ uptake data. Analysis of poly(A)(+)-RNA by Northern blot confirmed that CK1.4 cells, but not the parental line, expressed the exchanger. Expression of the exchanger was also observed in aortic myocytes and a renal epithelial cell line (LLC-MK2) but not in other lines of renal epithelial cells (MDCK, LLC-PK1) or human dermal fibroblasts. The cardiac exchanger produced substantial 45Ca2+ efflux from CK1.4 cells in response to hormone-evoked release of stored Ca2+. CK1.4 cells are an attractive model for studies of the regulation of the cardiac exchanger because they stably express sufficient exchanger for biochemical and immunological analysis. PMID- 8476013 TI - Functional expression of the rat anion exchanger AE2 in insect cells by a recombinant baculovirus. AB - We used baculovirus to transiently express a rat anion exchanger (AE2) in Spodoptera frugiperda (Sf9) insect cells. No detectable Cl(-)-HCO3- exchange activity was observed in wild type or sham-infected Sf9 cells, monitored using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, a pH-sensitive fluorescent dye. Functional expression of anion exchange activity in the AE2 recombinant baculovirus-infected cells was observed within the first day after infection and sustained over the next 3 days. The expressed AE2 anion exchange activity was Na+ independent and could be reversibly and irreversibly inhibited by the specific anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). The reversible inhibition was sensitive to the concentration of DIDS, with a half inhibition of 4 microM. These results indicate that the rat AE2 protein produced in the recombinant baculovirus-infected insect cells is inserted into the plasma membrane in a biologically active form that appears suitable for functional studies of AE2. PMID- 8476014 TI - Supernatant of endothelial cells exposed to laminar flow inhibits mesangial cell proliferation. AB - We investigated the effects of culture medium conditioned with endothelial cells exposed to hemodynamic shear forces on modulation of mesangial cell (MC) growth. Confluent monolayers of bovine aortic endothelial cells, grown in medium containing 10% fetal calf serum, were exposed to static or to laminar flow conditions for 24 h using a cone-and-plate device. Endothelial cell-conditioned medium was used to study the growth of bovine MC by [3H]thymidine uptake. The proliferative response of MC to fresh medium (containing 10% fetal calf serum) and to culture medium from endothelial cells under static flow [66.7 +/- 34.1 vs. 73.9 +/- 30.0 counts/min (cpm) x 10(-3)] was comparable. In contrast, medium conditioned with endothelial cells exposed to laminar shear stress of 8 dyn/cm2 almost completely abolished MC proliferation (5.8 +/- 6.9 cpm x 10(-3), P < 0.01). To establish whether this effect is due to endothelial cell production of a substance that inhibits MC proliferation or simply to metabolization of serum growth factors in the culture medium, we performed shear stress experiments using serum free medium and we added 10% fetal calf serum after shear exposure just before the proliferation assay. In this condition a significant antiproliferative effect of endothelial cell supernatant under laminar flow was obtained (27.7 +/- 23.4 vs. 68.8 +/- 45.8 cpm x 10(-3), laminar vs. static, P < 0.05), suggesting that endothelial cells under shear stress effectively produce a factor that inhibits MC proliferation. These results would suggest that local glomerular capillary blood flow could play a role in the regulation of MC mitogenesis. PMID- 8476015 TI - Transport of lactate and other monocarboxylates across mammalian plasma membranes. AB - Transport of L-lactate across the plasma membrane is of considerable importance to almost all mammalian cells. In most cells a specific H(+)-monocarboxylate cotransporter is largely responsible for this process; the capacity of this carrier is usually very high, to support the high rates of production or utilization of L-lactate. The best characterized H(+)-monocarboxylate transporter is that of the erythrocyte membrane, which transports L-lactate and a wide range of other aliphatic monocarboxylates, including pyruvate and the ketone bodies acetoacetate and beta-hydroxybutyrate. This carrier is inhibited by alpha cyanocinnamate derivatives and some stilbene disulfonates and has been identified as a protein of 35-50 kDa on the basis of purification and specific labeling experiments. Other cells possess similar alpha-cyanocinnamate-sensitive H(+) linked monocarboxylate transporters, but in some cases there are significant differences in the properties of these systems, sufficient to suggest the existence of a family of such carriers. In particular, cardiac muscle and tumor cells have transporters that differ in their Km values for certain substrates (including stereoselectivity for L- over D-lactate) and in their sensitivity to inhibitors. Mitochondria, bacteria, and yeast also possess H(+)-monocarboxylate transporters that share some properties in common with those in the mammalian plasma membrane but are adapted to their specific roles. However, there are distinct Na(+)-monocarboxylate cotransporters on the luminal surface of intestinal and kidney epithelia, which enable active uptake of lactate, pyruvate, and ketone bodies in these tissues. This article reviews the properties of these transport systems and their role in mammalian metabolism. PMID- 8476016 TI - Sorting and recycling efficiency of apical insulin binding sites during endocytosis in proximal tubule cells. AB - Intracellular traffic and recycling of apical insulin binding sites are examined in isolated, perfused proximal tubules. The endocytic binding sites were specific as revealed by 90% reduction in 125I-labeled insulin binding by 10(-5) M insulin. The traffic was followed by developing a chemical cross-linking method to covalently label the binding sites. Only 3% of cross-linked insulin-gold was transported to the lysosomes, reflecting high sorting and recycling efficiency. Correspondingly, only 4% of cross-linked 125I-insulin was degraded, and only 5% of the electron microscopy-autoradiographic grains was associated with lysosomes. No label was transferred to the Golgi apparatus; thus neither lysosomes nor Golgi apparatus is involved in the recycling. In contrast, approximately 40% of non cross-linked ligand was transferred to the lysosomes. Tubules first pretreated with cross-linker and then perfused with insulin-gold or 125I-labeled insulin like growth factor I revealed lysosomal accumulation and degradation at control levels. Thus the cross-linker does not interfere with membrane or protein processing. The study also provides evidence for a vesicular transtubular transport because insulin-gold was transcytosed to the basolateral part of the cells and to the intracellular spaces (0.5%). In contrast cross-linked label was never observed in intercellular spaces, suggesting sorting of apical binding sites, a mechanism contributing to maintenance of cell polarity. In conclusion, traffic, sorting, and recycling of binding sites take place with high efficiency. PMID- 8476017 TI - Endocytosis in proximal tubule cells involves a two-phase membrane-recycling pathway. AB - The aims of the present study were to examine the initial events of endocytosis with respect to migration, internalization, and recycling of protein binding sites on the luminal plasma membrane of genuine renal proximal tubule cells (not cultured cells), and in particular the sequential involvement of dense apical tubules (DAT). Isolated rabbit proximal tubules were first perfused at low temperature (9 degrees C) with insulin-gold to label the binding sites and then with disuccinimidyl suberate (DSS) for 20 min to covalently cross-link insulin gold and binding sites. The tubules were subsequently perfused for 4-30 min at 25 or 37 degrees C before fixation to follow the pathways of the binding sites. The present experimental approach allowed a temporal separation of the subcellular processes involved in endocytosis. The identity and organization of the different organelles were certified by serial sectioning of the experimental tubules. In tubules fixed directly at low temperature after cross-linking the label was located on the microvilli membranes and in plasma membrane invaginations. The labeling of microvilli decreased with time of perfusion at 25 degrees C in parallel with a simultaneous increase of labeling of invaginations, suggesting lateral migration of the binding sites. The invaginations pinched off from the surface to form endocytic vesicles. The binding sites were subsequently trafficked either to 1) tubular elongations from endocytic vesicles or small vacuoles, which again form DAT, or 2) in a later sequence trafficked to larger vacuoles, from which tubular elongations and DAT also form. The elongations formed the DAT that transported binding sites back to the luminal plasma membrane. Lysosomes and Golgi apparatus were not involved in membrane recycling. Thus the present study provides evidence for a two-phase recycling pathway of membrane proteins involved in endocytosis. PMID- 8476018 TI - Ca transport by plasma membrane and intracellular stores of gastric cells. AB - The relative Ca transport activities (i.e., of both pumps and leaks) of carbachol releasable intracellular stores and the basolateral plasma membrane of gastric parietal cells were studied using digital image processing of fura-2 fluorescence. Cells were treated with either carbachol (a cholinergic agonist) or thapsigargin (an inhibitor of microsomal Ca-adenosinetriphosphatase) or a combination of the two. Ca-free solutions were used to selectively investigate intracellular store release and plasma membrane pump activity, whereas Ca containing solutions were used to investigate Ca influx and refilling of the intracellular pool. In the resting cell depletion of the intracellular pool in Ca free solutions was 15-fold faster than control in the presence of thapsigargin, indicating the efficient (> 90%) recycling of leaked Ca by the store Ca pump. Stimulation with carbachol increased the rate of pool depletion by 70-fold, and this Ca flux out of the internal store was ten times larger than the flux across the plasma membrane. Thus the internal store has ten times greater fluxes (both leaks and pumps) than the plasma membrane during resting and stimulated conditions. After carbachol removal (i.e., reloading) the permeability of the internal store decreases, whereas increased influx across the plasma membrane persists until the store is refilled. Cytoplasmic Ca does not increase during refilling because the intracellular store pump operates eightfold faster than the plasma membrane pump, effectively sequestering Ca as quickly as it enters the cell. PMID- 8476019 TI - Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. AB - In ischemic organs, arachidonic acid (AA) metabolites and mostly prostaglandins (PGs) have been found to be released in high amounts. The mechanism for this AA metabolism activation and its physiological implications are not clear. Because endothelial cells are an important source of PGs and because they seem to be very rapidly affected by ischemia, we developed an in vitro model where human endothelial cells were submitted to hypoxia. An important specific activation of phospholipase A2 was observed during hypoxia, which was concomitant with a rise in cytosolic calcium concentration. Endothelial cells synthetize in normal conditions as a mean 1.42, 1.00, 7.69, and 26.92 ng/mg proteins of, respectively, PGE2, PGD2, PGF2 alpha, PGI2. An important increase of about five- to ninefold in the synthesis of the four PGs was observed during hypoxia, which followed the same kinetics as the PLA2 activation. This increase in PG synthesis was sensitive to cyclooxygenase inhibitors. During reoxygenation, PG synthesis decreased back to the basal level of resting cells, suggesting that cells were able to recover their homeostasis after hypoxia. These observations indicate that endothelial cells exposed to oxygen deprivation are a major source of PGs and could contribute to the high amounts of PG released in vivo in ischemic organs. PMID- 8476020 TI - Steroid hormone stimulation of Na+ transport in A6 cells is mediated via glucocorticoid receptors. AB - The A6 cell line derived from the toad kidney forms polarized, highly differentiated epithelial monolayers in culture and has been utilized as an experimental model for studying regulation of transepithelial Na+ transport by aldosterone. In the present study we evaluated the specific role(s) of glucocorticoid and mineralocorticoid receptors in mediating this enhanced electrogenic Na+ transport, which was measured experimentally as an increase in short-circuit current (Isc). Our data demonstrate that specific glucocorticoid agonists (100 nM), including RU 28362 and RU 26988, elicit "mineralocorticoid like" increases in Isc that are blocked by the glucocorticoid antagonist RU 38486 but are unaffected by mineralocorticoid antagonists including RU 28318 and RU 26752. The stimulatory effects of aldosterone (100 nM) were also blocked by RU 38486 and not by mineralocorticoid antagonists. These data extend earlier studies suggesting that in this cell line aldosterone mediates its physiological effects via binding with relatively low affinity (dissociation constant Kd congruent to 25-50 nM) to glucocorticoid receptors, despite the presence of apparently normal mineralocorticoid receptors. Our in vitro biochemical studies also demonstrate that A6 glucocorticoid receptor complexes can be thermally activated or transformed to DNA binding forms which exhibit altered elution profiles from anion-exchange resins. Thus, based on several criteria, these amphibian glucocorticoid receptors appear very similar to classical mammalian receptors and are capable of mediating all of the stimulatory effects of aldosterone on net Na+ transport. PMID- 8476021 TI - TNF-alpha induces endothelial cell F-actin depolymerization, new actin synthesis, and barrier dysfunction. AB - Tumor necrosis factor-alpha (TNF-alpha) influences pulmonary vascular endothelial barrier function in vitro. We studied whether recombinant TNF-alpha (rTNF-alpha) regulates endothelial barrier function through actin reorganization. Postconfluent bovine pulmonary artery endothelial cell monolayers were exposed to human rTNF-alpha (1,000 U/ml) and evaluated for 1) transendothelial [14C]albumin flux, 2) F-actin organization with fluorescence microscopy, 3) F-actin quantitation by spectrofluorometry, and 4) monomeric G-actin levels by the deoxyribonuclease I inhibition assay. rTNF-alpha induced increments in [14C]albumin flux (P < 0.04) and intercellular gap formation at > or = 2-6 h. During this same time, the endothelial F-actin pool decreased (P = 0.0064), with reciprocal increases in the G-actin pool (P < 0.0001). Prior F-actin stabilization with phallicidin protected against the rTNF-alpha-induced increments in G-actin (P < 0.002) as well as changes in barrier function (P < 0.01). Prior protein synthesis inhibition enhanced the rTNF-alpha-induced decrement in F-actin (P < 0.0001), blunted the G-actin increment (P < 0.002), and increased rTNF-alpha-induced changes in endothelial barrier function (P < 0.003). Therefore, rTNF-alpha induces pulmonary vascular endothelial F-actin depolymerization, intercellular gap formation, and barrier dysfunction. rTNF alpha also increased total actin (P < 0.02) and new actin synthesis (P < 0.002), which may be a compensatory endothelial cell response to rTNF-alpha-induced F actin depolymerization. PMID- 8476022 TI - Cytosolic free calcium regulation in response to acute changes in intracellular pH in vascular smooth muscle. AB - This study examined the mechanisms whereby alterations of intracellular pH (pHi) impact on free cytosolic calcium (Cai2+) in cultured rat aortic vascular smooth muscle cells (VSMC) assayed in the presence of HCO3/CO2. Rapid cell alkalinization, effected by the exposure to NH4Cl or removal of CO2 from the superfusate, produced a rapid increase in Cai2+. The rise in Cai2+ was markedly diminished when sarcoplasmic reticulum (SR) Ca2+ stores had been depleted by prior exposure to arginine vasopressin (AVP) in Ca(2+)-free media or when SR release and reuptake of Ca2+ were blocked by the addition of 3,4,5 trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), but was unaffected by the removal of external Ca2+ or inhibition of Ca2+ entry using NiCl2. Cell acidification also resulted in a rapid increase in Cai2+. This Cai2+ increase was most apparent when pHi was very low (< 6.6) and was unaffected by removal of external Ca2+ or NiCl2 addition. Unlike the effect of cell alkalinization, the increase in Cai2+ associated with cell acidification was not prevented by pretreatment with AVP or TMB-8. We conclude that, in cultured VSMC, acute intracellular alkalinization and, to a lesser extent, acidification result in release of Ca2+ from internal stores. Alkalinization increases Cai2+ by promoting its release from a store which is AVP and TMB-8 sensitive, most likely the SR. Cell acidification increases Cai2+ from an intracellular store(s) that is neither AVP nor TMB-8 sensitive. The increase in Cai2+ produced by cell acidification may be explained on the basis of cell buffering such that, as cytosolic H+ increases, it displaces Cai2+ from internal buffers with similar affinities for Ca2+ and H+. PMID- 8476023 TI - Cytosolic pH sensitivity of an expressed human NHE-1 Na(+)-H+ exchanger. AB - These studies examined the effects of protein kinase C activation and calmodulin inhibition on the amiloride-sensitive NHE-1 isoform of the Na(+)-H+ exchanger in defined host cells. Our objective was to define differences in the cellular regulatory responses using a specified isoform of the Na(+)-H+ exchanger. Suspended cells were loaded with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) and preacidified to a cytosolic pH of 6.2. Wild-type mouse Ltk- cells, human A-431 cells, and mutant mouse fibroblasts stably transfected with the human NHE-1 isoform (LAP+ cells) were examined to define the maximal rate of transport (Vmax) in response to 140 mM external Na+, the Hill stoichiometric coefficient, and the cytosolic pH at which the NHE-1 isoform was half-maximally stimulated (pH50). The mouse NHE-1 isoform had a greater affinity for cytosolic H+ than the human NHE-1 isoforms. Calmodulin antagonism with N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide reduced the Vmax and shifted the pH50 in the acidic direction, especially in the A-431 cells. Protein kinase C stimulation had a similar effect in A-431 cells and little effect in the wild-type (Ltk-) and transfected (LAP+) mouse cells. While the NHE-1 isoform contains several potential phosphorylation sites, the cellular milieu in which the isoform is expressed has an important effect on the modulation of NHE-1 activity. PMID- 8476024 TI - Extracellular ATP-induced regulation of epidermal growth factor signaling in cultured renal LLC-PK1 cells. AB - We investigated the effect of extracellular ATP on the interaction of epidermal growth factor (EGF) with its receptor in cultured renal epithelial cells, LLC PK1. Pretreatment with ATP, but not adenosine, inhibited the binding of 125I labeled EGF. The inhibition demonstrated by ATP resulted from a decrease in the affinity of EGF receptors for its ligand, with no change in the number of EGF receptors. Incubation of phorbol 12-myristate 13-acetate (PMA) for 30 min mimicked the ATP-mediated inhibition. On the other hand, prolonged pretreatment with PMA, which leads to disappearance of protein kinase C activity, reversed the inhibition. In addition, pretreatment with the protein kinase C inhibitor 1-(5 isoquinoline sulfonyl)-2-methylpiperazine prevented the ATP-mediated inhibition. ATP triggered an increase in inositol 1,4,5-trisphosphate levels and translocation of protein kinase C from cytosol to membranes, consist with the stimulation of phospholipase C and the activation of protein kinase C. These results demonstrate that extracellular ATP attenuates the ligand binding affinity of EGF receptor via the stimulation of phospholipase C, leading to the activation of protein kinase C in the LLC-PK1 cells. PMID- 8476025 TI - Protective effects of adenosine in the perfused rat heart: changes in metabolism and intracellular ion homeostasis. AB - Increased concentrations of intracellular H+, Na+, and Ca2+ have been observed during ischemia, and these ionic alterations have been correlated with several indexes of cell injury in a number of studies. Recently, adenosine was proposed to play a role in ischemic preconditioning, since adenosine antagonists block the protective effects of these brief intermittent periods of ischemia and reflow. In this study we evaluated the protective effects of adenosine (20 microM) on high energy phosphate metabolism, H+ and Ca2+ accumulation, and glycolytic rate during 30 min of no-flow ischemia. Adenosine was observed to slow the onset of contracture (7.0 +/- 0.9 min) and to improve left ventricular developed pressure (62 +/- 7% of initial) during reperfusion compared with untreated hearts (5.0 +/- 0.6 min and 18 +/- 5%, respectively). Intracellular Ca accumulation at the end of 30 min of ischemia was higher in the untreated (2,835 +/- 465 nM) than in the adenosine-treated (2,064 +/- 533 nM) hearts, while intracellular pH fell more in the untreated (5.85 +/- 0.17) than in the adenosine-treated hearts (6.27 +/- 0.16). Glycolytic rate and the rate of ATP decline were significantly attenuated in the adenosine-treated hearts during ischemia. Thus adenosine treatment slowed the rate of metabolism and delayed the accumulation of H+ and Ca2+ during ischemia, resulting in better recovery of function upon reflow. PMID- 8476026 TI - Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. AB - Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature. PMID- 8476027 TI - Estrogen-induced left ventricular chamber enlargement in ewes. AB - We studied the chronic effect of administration of a single large intramuscular dose of 17 beta-estradiol on left ventricular chamber size and output in the ewe. Fourteen oophorectomized ewes were successfully instrumented and studied, with measurements made of left ventricular, aortic, right and left atrial pressures, left ventricular stroke volume, and left ventricular minor axis dimension. Unanesthetized ewes were studied before and 1, 2, and 3 wk after intramuscular administration of 0.6 mg/kg 17 beta-estradiol (7 ewes) or 1.5 ml sesame oil placebo (7 ewes). Left ventricular end-diastolic pressure-end-diastolic dimension (LVEDP-EDD) and left ventricular end-diastolic pressure-stroke volume (LVEDP-SV) relationships were quantified during graded inferior vena caval occlusion and volume infusion. Left ventricular end-diastolic diameter was larger after estrogen but not after placebo administration. The LVEDP-EDD relationship shifted progressively rightward, indicating left ventricular chamber enlargement in the estrogen group but was unchanged in the placebo group. The plateau limb of the LVEDP-SV relationship in the estrogen group shifted up from a mean stroke volume of 77.1-89.5 ml/beat and did not change in the placebo group. We conclude that administration of a single large intramuscular dose of 17 beta-estradiol resulted in left ventricular chamber enlargement and increased stroke volume in the ewe. PMID- 8476028 TI - Whole body and splanchnic oxygen consumption and blood flow after oral ingestion of fructose or glucose. AB - The contribution of the splanchnic tissues to the initial 2-h rise in whole body energy expenditure after ingestion of glucose or fructose was examined in healthy subjects. Indirect calorimetry and catheter techniques were employed to determine pulmonary gas exchange, cardiac output, splanchnic blood flow, splanchnic oxygen uptake, and blood temperatures before and for 2 h after ingestion of 75 g of either fructose or glucose in water solution or of water only. Fructose ingestion was found to increase total oxygen uptake by an average of 9.5% above basal levels; the corresponding increase for glucose was 8.8% and for water only 2.5%. The respiratory exchange ratio increased from 0.84 in the basal state to 0.97 at 45 min after fructose ingestion and rose gradually after glucose to 0.86 after 120 min. The average 2-h thermic effect, expressed as percent of ingested energy, was 5.0% for fructose and 3.7% for glucose (not significant). Splanchnic oxygen consumption did not increase measurably after ingestion of either fructose or glucose. The arterial concentration of lactate rose, arterial pH fell, and PCO2 remained essentially unchanged after fructose ingestion. Glucose, but not fructose, elicited increases in cardiac output (28%) and splanchnic blood flow (56%). Fructose, but not glucose, increased arterial blood temperature significantly. It is concluded that both fructose and glucose-induced thermogenesis occurs exclusively in extrasplanchnic tissues. Compared with glucose, fructose ingestion is accompanied by a more marked rise in CO2 production, possibly reflecting an increased extrasplanchnic oxidation of lactate and an accumulation of heat in the body. PMID- 8476029 TI - Impact of conceptus mass on glucose disposal rate in pregnant women. AB - The impact of an increasing fetal and placental mass on maternal glucose disposal rate (GDR) was studied in 17 pregnant women. Eleven pregnancies were singleton pregnancies, five were twin and one was a triplet pregnancy. Both the maternal fasting glucose concentration [Glc] and the total fetal and placental weight (W) were significantly correlated with an increased maternal GDR. Glucose concentration and conceptus weight were interdependent. The multiple linear regression of glucose disposal rate on glucose concentration and total weight is given by GDR = -1.573 + 0.176W + 0.932[Glc] +/- 0.24, r2 = 0.52, P < 0.01. These data are utilized to estimate the glucose utilization rate of the human conceptus at a fasting glucose concentration of 3.9 mM with a range of 10-15 mg.kg-1.min-1. Maternal GDR increases with increasing glucose concentration at a rate similar to that reported for newborn infants, consistent with a high glucose utilization by the uterus. PMID- 8476030 TI - Role of cytosolic calcium in regulation of cytoskeletal gene expression by insulin. AB - Insulin and calcium ionophores rapidly stimulated transcription of the cytoskeletal beta- and gamma-actin genes in serum-deprived rat H4-II-E hepatoma cells. The calcium ionophore A23187 (1 microM) stimulated transcription of the beta-actin gene by 7.3-, 5.4-, and 2.6-fold and the gamma-actin gene by 5.9-, 5.6 , and 2.6-fold at 15, 30, and 60 min, respectively. Ionomycin (1 microM) similarly increased beta- and gamma-actin transcription. Insulin stimulated beta actin transcription 11.4-fold and gamma-actin 8.4-fold at 30 min. alpha-Tubulin transcription was induced by both insulin and calcium ionophores but to a lesser degree. The effects of A23187 or ionomycin together with insulin for 30 min were no greater than those of insulin alone. Insulin alone, however, did not significantly increase measurable intracellular calcium concentrations in fura-2 loaded cells. When cytosolic calcium was chelated using quin2 acetoxymethyl ester, the ability of A23187 to increase beta- and gamma-actin transcription was completely abolished, whereas insulin's ability to stimulate actin transcription was only partially inhibited. This suggests that the regulation of gene transcription by insulin may include calcium-dependent pathways but strongly implies that calcium-independent pathways are also utilized. PMID- 8476031 TI - Time of day of birth and absence of endocrine and uterine contractile activity rhythms in sheep. AB - To determine whether 24-h rhythms characterize hormone secretion and uterine activity in the pregnant sheep, blood samples were drawn every 1-4 h for 48 h from ewes and fetuses from day 120 of gestation to term. Repetitive 24-h rhythms were absent for cortisol, progesterone, and prolactin in maternal and fetal circulation and for hourly mean uterine contraction rate and amplitude. To test whether photoperiod or pineal melatonin contributes to the absence of rhythms, pineal-intact and pinealectomized ewes and their fetuses were studied in reverse photoperiod. Again, there was little evidence to suggest 24-h endocrine rhythms except for prolactin in two fetuses by cosinor analyses. Prolactin concentrations were increased in pinealectomized ewes and their fetuses. In the apparent absence of rhythms, 20 of 21 pineal-intact ewes gave birth at night; however, 6 out of 7 pinealectomized ewes gave birth during the day. Thus photoperiod and the maternal pineal gland profoundly influenced the time of day of birth in the absence of circadian endocrine or uterine activity rhythms. PMID- 8476032 TI - Postprandial plasma triacylglycerols in rats under alpha 1-adrenergic blockade. AB - The present studies evaluated the effect of prazosin, a selective alpha 1 adrenergic antagonist, on some metabolic determinants of triacylglycerol-rich lipoproteins. Plasma triacylglycerols (TG), TG secretion rate, TG removal rate, plasma insulin, and glucose were evaluated postprandially in animals fed a high sucrose meal. In the fasted state plasma TG, glucose, and insulin concentrations were minimally affected by prazosin. There was a significant postprandial elevation in plasma TG levels that was larger after ingestion of a meal containing corn oil than after intake of a fat-free meal. Prazosin totally blunted the postprandial elevation in plasma TG independently of the presence (P < 0.004) or absence of dietary fat (P < 0.01). In the postprandial phase after ingestion of a fat-free, high-sucrose meal, prazosin decreased the rate of secretion of TG into the circulation (-54%, P < 0.0003) and accelerated twofold the clearance of an injected fat emulsion (P < 0.02). The postprandial elevations in plasma insulin and glucose were significantly potentiated by administration of prazosin before intake of the fat-free meal. These results indicate that prazosin prevented the postprandial elevation in plasma TG that followed the ingestion of a high-sucrose meal. The results also demonstrate that the alpha 1-blocker exerted its action both by decreasing TG secretion and by increasing the rate of removal of circulating TG. PMID- 8476033 TI - Methods for assessment of the rate of onset and offset of insulin action during nonsteady state in humans. AB - Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52:215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU.kg-1 x min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187:15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within approximately 40 min (P < 0.01 vs. other methods). The hot-GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot GINF and variable-pV methods avoid non-steady-state error introduced by the fixed pV method and provide concordant assessments of the rate of onset and offset of insulin action. PMID- 8476034 TI - Hepatic and extrahepatic insulin action in humans: measurement in the absence of non-steady-state error. AB - The isotope dilution technique has been extensively used to assess insulin action in humans. To determine if nonsteady state (NSS) has led to erroneous estimates of hepatic and extrahepatic insulin sensitivity, we measured glucose turnover in healthy subjects during infusion of insulin at rates of 0.25, 0.6, and 2.0 mU.kg 1.min-1. Turnover was calculated using Steele's traditional NSS equations [fixed effective volume (pV) method] as well as with methods [radioactive infused glucose (hot-GINF) or variable pV] designed to minimize NSS error. In contrast to the fixed-pV method, both the hot-GINF and variable-pV methods indicated that several hours were required for suppression of hepatic glucose release at all insulin concentrations and that small increases in plasma insulin (approximately 100 pmol/l) had comparable effects on glucose disappearance and hepatic glucose release. Nevertheless, despite these differences, when turnover during the final hour of the insulin infusions was plotted vs. the prevailing insulin concentration, all three methods yielded similar insulin dose-response curves for suppression of hepatic glucose release. Thus despite previous errors in measurement of glucose turnover, the widely accepted belief that the human liver is exquisitely sensitive to small changes in insulin is correct. PMID- 8476035 TI - Effects of protein restriction and acute refeeding on leucine and lysine kinetics in young men. AB - To explore the effects of altered protein intake on the uptake and utilization of dietary amino acids in human subjects, six healthy male Massachusetts Institute of Technology students were studied during three dietary periods each of 9 days, with tracer infusion studies conducted on days 8 and 9. During one period the diet provided a generous protein intake (1.5 g.kg-1.day-1) and during the other two a low-protein intake (0.1 g.kg-1.day-1). Tracer infusions (fed state) were given while subjects received either a liquid formula, supplying the prior protein intake or (on day 9) a generous intake. Combinations of [2H3]Leu and [13C]Leu and of [15N]Lys and [2H4]Lys were given via continuous intravenous or intragastric infusion for 4 h to estimate leucine kinetics and the first-pass splanchnic uptake of tracer. Dietary-induced changes in leucine flux and oxidation were similar irrespective of the tracer and/or route of administration and sampled pool (leucine or KIC) used for calculation. Estimates of absolute changes in the rates of leucine disappearance via nonoxidative metabolism (protein synthesis) and of appearance via protein breakdown depended on the route of [13C]Leu administration. However, it appears that both altered rates of protein synthesis and breakdown contribute to the adaptations required in the body nitrogen economy when protein intakes are restricted and subsequently resupplied. From the intragastric [13C]Leu protocol, the first-pass splanchnic uptake of tracer was the same (approximately 30%) for generous, low-protein, and refed conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476036 TI - Lowering plasma free fatty acid levels improves insulin action in conscious pregnant rabbits. AB - Acute elevation in plasma free fatty acid (FFA) levels in nonpregnant rabbits simulates some aspects of insulin resistance observed in late pregnancy. The aim of this study was therefore to evaluate whether lowered FFA induced by nicotinic acid (NA) infusion can improve insulin action in pregnant rabbits. To assess insulin sensitivity we applied euglycemic hyperinsulinemic clamp without (control study) or with concomitant NA infusion (NA study; infusion started 150 min before the glucose clamp) in conscious virgin and pregnant rabbits after an 18-h fast. A primed constant infusion of [3-3H]glucose was used to measure total glucose disposal and hepatic glucose production. Hyperinsulinemia, in association with NA infusion (NA study) brings about a significantly greater stimulation of total glucose disposal in both pregnant (approximately 30%) and nonpregnant (approximately 35%) rabbits compared with the control study. A more pronounced inhibition of hepatic glucose production occurred in NA study in pregnant rabbits (approximately 30 vs. approximately 10%) but it did not reach a statistical significance, whereas there was a total inhibition in nonpregnant rabbits. We conclude that acute decrease in plasma FFA levels mainly improves insulin action at the site of glucose utilization. These results therefore suggest that elevated FFA would contribute to the peripheral insulin resistance in late pregnancy. PMID- 8476037 TI - Effects of muscle activity and fiber composition on glucose transport and GLUT-4. AB - We examined glucose uptake and GLUT-4 in rat muscles [soleus (Sol), plantaris (PL), extensor digitorum longus (EDL), tibialis anterior, and the red and white gastrocnemius (WG)]. In the normally innervated perfused rat hindlimb muscles the proportion of oxidative fibers was highly correlated with the muscle's insulin stimulated 3-O-methyl-D-glucose (3-MG) uptake (R2 = 0.78) and GLUT-4 content (r = 0.94). Insulin-stimulated 3-MG uptake and GLUT-4 were also highly correlated (R2 = 0.996). In 3-day denervated muscles, insulin-stimulated 3-MG uptake was reduced in all six muscles (-41 to -14.6%, P < 0.05), and GLUT-4 content was also reduced (-87.5 to -34.9%), except in the WG and EDL (P > 0.05). A very high correlation was observed between the decrements in GLUT-4 (%) and the decrements in 3-MG uptake (%; r = 0.99). The relatively greater loss in muscle activity (%) due to denervation in the Sol compared with the PL coincided with the reductions (%) in GLUT-4 and 3-MG uptake. These studies demonstrate that glucose uptake and GLUT-4 are regulated by insulin-independent means, namely the oxidative capacity of the muscle and the normal activity level of the muscle. PMID- 8476038 TI - Sleep-promoting effects of growth hormone-releasing hormone in normal men. AB - Growth hormone-releasing hormone (GHRH) promotes rapid-eye-movement (REM) and non REM sleep in animals, but there is little direct evidence for a hypnogenic action of GHRH in humans. In the present study, the possible somnogenic effects of intravenous bolus injections of a dose of GHRH eliciting physiological elevations of GH secretion in healthy young men were investigated. GHRH (0.3 micrograms/kg body wt) was given in early sleep [i.e., 1st slow-wave (SW) period], late sleep (i.e., 3rd REM period), and early sleep after sleep deprivation until 0400 h (i.e., 1st SW period). In the absence of sleep deprivation, injection of GHRH in early sleep did not modify SW sleep but increased REM sleep. GHRH administration in the third REM period was followed by a marked decrease of wake and an almost 10-fold increase in SW sleep. When GHRH was administered during the first SW period after sleep deprivation until 0400 h, the duration of wake decreased. Thus GHRH has sleep-promoting effects in young adults, particularly when given at a time of decreased sleep propensity. PMID- 8476039 TI - Contribution of muscle and liver to glucose-fatty acid cycle in humans. AB - To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin. Suppression of HGP by insulin was impaired by elevated plasma FFA levels. Furthermore, the increase in plasma FFA was associated with a 20% reduction in total glucose metabolism (P < 0.01), which was completely accounted for by a reduction in the rate of glucose oxidation. Although the fractional activity of GS was increased by insulin, elevation of plasma FFA had no influence on this key enzyme of glycogen synthesis. In addition, the activities of PDH and CPT were uninfluenced by the elevation of FFA, suggesting that oxidative processes in skeletal muscle were not a major target for the operative glucose fatty acid cycle under the current conditions. Taken together, the data indicate that the interaction between FFA and glucose metabolism also involves impaired suppression of HGP by insulin. PMID- 8476040 TI - Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats. AB - This study was carried out to analyze age-related changes on amino acid and insulin effects on muscle and liver protein synthesis. Conscious male rats, aged 12 (adult) and 24 (old) mo, were infused for 90 min with either saline, amino acids, or amino acids with insulin and glucose. Protein synthesis was measured during the last 15 min of infusion (flooding dose of valine with L-[2,3,4 3H]valine). Gastrocnemius protein mass was 29% lower in old rats than in adults. However, basal muscle absolute synthesis rates were unchanged with age, and fractional synthesis rates (FSR) were increased. Amino acids significantly stimulated muscle FSR to a similar extent (18-20%) in adult (P < 0.01) and old rats (P = 0.03 when variability introduced by muscle atrophy was taken into account by a variance-covariance analysis). Insulin did not elicit any additional effect. Liver protein synthesis did not change with age or in response to infusions. We conclude that, despite an age-related loss of muscle proteins, capacity of muscle protein synthesis to be stimulated is preserved with age. PMID- 8476041 TI - Carbonic anhydrase III in obese Zucker rats. AB - Proteins from 5- to 7-wk-old lean and obese Zucker rats were separated by one dimensional sodium dodecyl sulfate (SDS) and two-dimensional SDS-isoelectric focusing-polyacrylamide gel electrophoresis. Laser densitometry revealed an obesity-related decrease in the concentration of a 28-kDa cytosolic adipocyte protein, the most abundant protein in adipocytes from lean Zucker rats. Microsequencing revealed the identity of this protein to be carbonic anhydrase III (CA III). The identity and obesity-related decrease was further confirmed using isoform-specific antisera and CA III enzyme activity measurements made by 18O mass spectrometry. Immunoblotting studies also revealed that CA III is present in at least two charge isoforms in adipocytes. Our data indicate that lean Zucker rat adipocytes may represent the richest source of CA III in nature (24% of the cytosolic protein content). An obesity-related decrease in both the concentration and activity of CA III was observed in two lipogenic tissues, liver and white fat, but not in soleus muscle. Adipocyte CA III activity was no longer depressed when hyperinsulinemic obese rats were made insulin deficient by streptozotocin injection. This suggests that the obesity-related decrease in CA III may be related to the hyperinsulinemia as well as to the insulin hyperresponsiveness that adipocytes from obese Zucker rats of this age display. PMID- 8476042 TI - Alterations in hypothalamic NPY and CRF in anorexic tumor-bearing rats. AB - Regional hypothalamic concentrations of neuropeptide Y (NPY) and corticotropin releasing factor (CRF), respectively a stimulant and an inhibitor of feeding behavior, were investigated in hypothalamic nuclei in rats carrying the Yoshida sarcoma. Tumor-bearing rats (n = 10), non-tumor-bearing controls (n = 10), and food-restricted rats (n = 10), which did not carry tumors but were pair-fed to match the reduced food intake of the tumor-bearing group, were studied after 10 days. NPY concentrations in the arcuate nucleus (ARC, the main site of NPY synthesis) were significantly increased above controls (P < 0.01) in both tumor bearing and food-restricted groups. However, NPY concentrations in the paraventricular nucleus (PVN, an NPY-sensitive site of NPY release) showed opposing changes, with a 25% decrease (P = 0.052) in the tumor-bearing but a 48% increase (P < 0.01) in the food-restricted group. CRF concentrations in both the PVN and the ARC were significantly reduced (P < 0.01) in the food-restricted group, but remained close to control values in the tumor-bearing group (P not significant). Changes in hypothalamic appetite-regulating neuropeptides in cancer anorexia, which may result from the action of cytokines produced by a host defense response or the tumor itself, may account for reduced feeding. Such changes may include impaired activity of NPY or failure of CRF activity to be suppressed after underfeeding and weight loss. PMID- 8476043 TI - Energy metabolism and adenine nucleotide degradation in twitch-stimulated rat hindlimb during ischemia-reperfusion. AB - The purpose of this study was to characterize twitch tension and energy metabolism in ischemic, stimulated rat hindlimb to determine its suitability as a rapid time course model of ischemia-reperfusion injury. After 15 min equilibration, rat hindlimbs were stimulated (1-Hz twitches, 0.2 ms pulse duration, 15 V) for 5 min (control, n = 8). This twitch protocol was maintained throughout the ischemic and reperfusion periods. The control period was followed by 5, 20, or 40 min of ischemia (ligation of femoral artery and vein) or 40 min of ischemia with 0, 5, or 20 min of reperfusion (removal of ligature). The soleus [89% slow oxidative (SO)] and the white gastrocnemius [WG; 91% fast glycolytic (FG)] were analyzed for phosphocreatine (PCr), adenine nucleotides, glycogen, and glycolytic intermediates. Ischemia was characterized by progressive decreases in twitch tension, high-energy phosphagens, total adenine nucleotides (TAN), and glycogen. Also, energy metabolism was altered at a greater rate in WG than in soleus. Reperfusion resulted in a recovery in PCr and lactate, with little change in ATP, TAN, or glycogen. The inability to resynthesize adenine nucleotides and glycogen during reperfusion is characteristic of damaged skeletal muscle. The extent of the metabolic alterations in SO and FG muscles during twitch stimulation was comparable with previously reported noncontracting ischemia protocols of 2-4 and 4-7 h in length, respectively. The present study demonstrates that twitch stimulation of ischemic skeletal muscle is a useful model for inducing rapid metabolic changes and an ischemic insult comparable to prolonged noncontracting ischemia-reperfusion models. PMID- 8476044 TI - Dietary lysine requirement of young adult males determined by oxidation of L-[1 13C]phenylalanine. AB - Lysine requirement was determined in seven adult males by examining the effect of varying dietary lysine intake on phenylalanine flux and oxidation under dietary conditions of adequate energy and phenylalanine (14 mg.kg-1 x day-1) and excess tyrosine (40 mg.kg-1 x day-1). Phenylalanine flux was determined from primed, constant intravenous infusions of L-[1-13C]phenylalanine (1.2 mg.kg-1 x day-1) and L-[ring-2H5]phenylalanine (0.5 mg.kg-1 x day-1) and measurement of isotopic enrichments of phenylalanine in plasma. Phenylalanine flux was not affected by graded increases in dietary lysine intake or by the isotope infused. Mean phenylalanine conversion to tyrosine was low (3.4%) and not significantly affected by lysine intake. Phenylalanine oxidation, estimated from the rate of 13CO2 released in expired air during the infusion of L-[1-13C]phenylalanine, decreased linearly as lysine intake increased to a break point that was interpreted as the mean dietary lysine requirement (37 mg.kg-1 x day-1). At lysine intakes of > 37 mg.kg-1 x day-1 phenylalanine oxidation was low and constant. Plasma lysine concentrations supported this estimate of requirement. These data show that: 1) indicator amino acid oxidation can be used as a new method to determine amino acid requirements of humans and 2) the lysine requirement of adult males is three times greater than the World Health Organization recommendation of 12 mg.kg-1 x day-1. PMID- 8476045 TI - Type I collagen gene regulation and the molecular pathogenesis of cirrhosis. AB - Cirrhosis is characterized by an increased deposition of extracellular matrix proteins, including type I collagen. Type I collagen is a product of two genes, alpha 1(I) and alpha 2(I), which are generally coordinately regulated. Since expression of type I collagen genes is increased during cirrhosis, understanding the structure and function of the regulatory components of the type I collagen genes should provide insight into the molecular pathogenesis of cirrhosis. This review will analyze the collagen alpha 1(I) gene with respect to chromatin structure, DNA methylation, regulation by agonists, and DNA-protein interactions. PMID- 8476046 TI - Motor cycles with phase III in antrum are associated with high motilin levels and prolonged gallbladder emptying. AB - We examined the relationship of interdigestive gallbladder emptying with the different phases of the migrating motor complex (MMC) and with plasma levels of cholecystokinin (CCK) and motilin. In 10 volunteers 20 cycles of the MMC were recorded. In 11 cycles phase III occurred in antrum and duodenum (group 1). In nine cycles phase III was observed only in duodenum (group 2). In group 1 gallbladder emptying started at 30% of total cycle length and continued until the end of the cycle. Maximal gallbladder emptying was 33.3 +/- 3.3% (SE). In group 2 gallbladder emptying also started at 30% of total cycle length but ended at 60%. Maximal gallbladder emptying in this group was 24.3 +/- 3.1% (P < 0.05). Motilin levels were higher in group 1 than in group 2 during phase IIB (240.1 +/- 28.5 and 142.1 +/- 30.9 pg/ml, respectively, P < 0.05) and during phase III (210.8 +/- 24.3 and 93.5 +/- 12.5 pg/ml, respectively, P < 0.05). We conclude that: 1) phase III activities starting in the antrum are preceded by greater and prolonged gallbladder emptying, higher motilin levels, and higher intraduodenal bile acid concentrations than phase III activities starting in the duodenum and 2) no relationship between interdigestive gallbladder motility and CCK levels could be demonstrated. PMID- 8476047 TI - Prostaglandin E2 downregulates Kupffer cell production of IL-1 and IL-6 during hepatic regeneration. AB - The mammalian liver possesses the ability to regenerate to its original size after a 70% partial hepatectomy (PHx). The capacity of rat Kupffer cells (KC) isolated at specific intervals after PHx to produce interleukin (IL)-1, IL-6, and prostaglandin E2 (PGE2) in response to endotoxin [lipopolysaccharide (LPS)] stimulation was evaluated in standard RPMI 1640 (1,200 microM L-arginine) and arginine-depleted RPMI 1640 (< 10 microM L-arginine) media. Because KC function in an environment in which high arginase activity results in negligible L arginine levels, the 10 microM L-arginine RPMI 1640 was used to simulate the hepatic microenvironment. Regenerating liver KC 12-120 h after PHx responded to LPS with a significantly greater (P < 0.05) production of IL-1 and IL-6 in standard RPMI 1640. This enhancement of regenerating liver KC to produce IL-1 and IL-6 was increased (P < 0.05) by placing these same KC in 10 microM arginine RPMI 1640 culture media. During the same time period, regenerating liver KC produced significantly elevated (P < 0.01) PGE2, again with greater differences in the low arginine media. In vivo KC PGE2 blockade by indomethacin (5 mg/kg) significantly (P < 0.05) inhibited hepatic regeneration. When the cyclooxygenase inhibitor indomethacin (10 microM) was added to cultures, the production of PGE2 by KC was prevented, and in arginine-depleted cultures, IL-1 and IL-6 production was upregulated (P < 0.05). We conclude that during hepatic regeneration, KC IL-1 and IL-6 production is elevated and is controlled in an autoregulatory fashion by elevated KC PGE2 production. PMID- 8476048 TI - Reconstitution of intestinal Na(+)-phosphate cotransporter. AB - The rabbit intestinal brush-border membrane Na(+)-phosphate cotransporter was purified from sodium dodecyl sulfate (SDS)-brush-border membrane vesicles (BBMV) protein (SDS-treated Ca(2+)-precipitated BBMV) by a three-column chromatography protocol. The purification included a preparative scale chromatofocusing chromatography column over the pH range from 7.4 to 4 after solubilization in 3 [(3-cholamidopropyl)-diamethylammonia]-1-propanesulfonate (CHAPS), a chromatofocusing column over the pH range from 5.6 to 4 after solubilization in n octyl glucoside, and gel filtration chromatography on a Sephacryl S-200 column. Verification of Na(+)-phosphate cotransporter purification involved substrate affinities, substrate stoichiometry, and inhibitor sensitivity after proteoliposome reconstitution and SDS-polyacrylamide gel electrophoresis (PAGE). After gel filtration Na(+)-dependent phosphate uptake was 3,300-fold enriched compared with the cell homogenate. A single 130-kDa polypeptide was visualized by SDS-PAGE under reducing conditions using silver stain. The coenrichment of this 130-kDa polypeptide and proteoliposome reconstituted Na(+)-dependent phosphate uptake suggest that the intestinal brush-border membrane Na(+)-phosphate cotransporter has been purified and proteoliposome reconstituted. PMID- 8476050 TI - The computer as referee in the analysis of human small bowel motility. AB - The aim of this study was to determine whether visual analysis of graphic records of small bowel motility is a reliable method of discriminating pressure events caused by bowel wall contraction from those of extraenteric origin and to compare this method with computerized analysis. Each of six independent observers was supplied with the same pair of records of 1 h of fasting diurnal duodenojejunal motility, acquired with a 3-channel ambulant data-logging system; one record included many artifacts due to body movement while the other did not. The observers were asked to identify and classify pressure events and to measure the duration and amplitude of "true" contractions. A computer program for on-line analysis is described; the algorithm was designed to overcome the problems of a variable baseline and sudden changes in pressure due to body movements that are unavoidable in prolonged recording from the small bowel of ambulant subjects. For regular contractions (phase III of migrating motor complex) there was good agreement between observers but not for irregular contractions, particularly when movement artifacts were abundant. When the observers were asked to repeat the analysis 6 mo later, there was poor agreement with their original identification of irregular contractions and artifacts. There was, however, good agreement between the computer analysis, which was totally reproducible, and the median decisions of the observer group; this agreement supports the validity of our computer algorithm. We conclude that computer analysis is not merely a valuable ergonomic aid for analysis of large quantity of data acquired in prolonged ambulatory monitoring, but also that, even for brief recordings, it provides a standard of reproducibility unmatched by "expert" inspection. Visual analysis is unreliable and thus susceptible to subjective bias; this may, in part, account for conflicting reports of small bowel motility under similar conditions reported by different workers in our own and other laboratories. PMID- 8476049 TI - Intestinal permeability in allergic rats: nerve involvement in antigen-induced changes. AB - In vivo uptake of the probe 51Cr-labeled EDTA from the jejunum of egg albumin (EA)-sensitized rats was compared with controls at baseline and after intraluminal antigen challenge. Probe recovery in blood was 60-80% greater in sensitized animals during the baseline period, suggesting that sensitization resulted in increased intestinal permeability. Sensitized, but not control, rats demonstrated a 15-fold increase in 51Cr-EDTA uptake after intraluminal antigen; no change occurred with an unrelated protein. Macromolecular recovery was also enhanced in sensitized animals, since serum levels of immunoreactive EA were elevated 14-fold compared with controls. Antigen challenge was accompanied by biochemical (protease release) and morphological (reduced numbers) evidence of mast cell degranulation in sensitized rats. The neurotoxin tetrodotoxin (applied directly to ligated jejunal segments) inhibited EA-induced uptake of 51Cr-EDTA and antigen. In isolated jejunum from sensitized rats, tetrodotoxin reduced secretory responses to luminal, but not serosal, antigen. These results indicate that neural factors may influence the uptake of molecules from the gut lumen during intestinal anaphylaxis. PMID- 8476051 TI - Kainic acid injection into medullary raphe produces gastric lesions through the vagal system in rats. AB - There is little evidence of a role of nuclei in the brain stem, other than the dorsal motor nucleus of the vagus nerve in the medulla oblongata, in terms of central mechanisms for gastric ulcer formation. Recent reports suggest that the medullary raphe nuclei may be involved in the central regulation of gastric functions such as gastric acid secretion and motility. In the present study, we examined whether neurons in the nucleus raphe obscurus (NRO) played a significant role in the formation of gastric ulcers with the use of Sprague-Dawley rats. First, we determined whether excitation of the medullary raphe resulted in the development of gastric lesions. Chemical stimulation of neurons in the NRO by kainic acid produced gastric erosions within 4 h in 24-h fasted rats. Saline tested under the same conditions did not modify the integrity of the gastric mucosa. It was also demonstrated that kainic acid injection outside the raphe obscurus boundaries failed to develop gastric lesions. Next, we examined the effects of the vagal system on the gastric lesion formation induced by stimulation of the raphe nucleus. Bilateral gastric branch vagotomies completely prevented the development of the raphe nucleus-provoked gastric mucosal damage. All these results suggest, for the first time, that excitation of neurons in the medullary raphe obscurus induces gastric ulceration through vagal stimulation. PMID- 8476052 TI - Duodenal lipid inhibits gastric acid secretion by vagal, capsaicin-sensitive afferent pathways in rats. AB - Neural and endocrine pathways mediate the inhibitory effects of intestinal fat on gastric acid secretion. To study whether vagal and/or spinal afferent nerves contribute to the neural component of the enterogastric reflex, the sensory neurotoxin capsaicin was applied topically either to the vagus nerves bilaterally or to the celiac-superior mesenteric ganglia in rats with chronic gastric and duodenal fistulas. In lightly restrained, awake rats acid secretion was stimulated for 2 h by continuous intragastric perfusion with 8% peptone and was measured by extragastric titration to pH 5.5. Duodenal lipid perfusion (0-20%) during the 2nd h caused inhibition of peptone-stimulated acid output. Acid output was inhibited by 81% during 5% lipid perfusion of the duodenum and was restored after capsaicin treatment of the vagus nerves. In contrast, capsaicin treatment of the celiac ganglion did not alter the acid inhibitory response to any dose of intestinal lipid. Basal and maximum acid outputs were not significantly different among rats treated by either method with capsaicin. The neural component of the enterogastric reflex in awake rats is mediated in part by a capsaicin-sensitive, vagal-afferent neural reflex. PMID- 8476053 TI - Adenosine is a mediator of ethanol-induced gastric vasodilation in dogs. AB - The purpose of this study was to assess the role of histamine, adenosine, and prostaglandins as mediators of ethanol-induced gastric vasodilation. In an ex vivo segment of canine stomach, vasodilation occurred within the first minute of replacing luminal saline with ethanol (40% vol/vol). Ethanol caused vascular resistance to progressively decrease by approximately 53% compared with control values. In other experiments, intra-arterial infusion of histamine (300 ng/ml) or adenosine (30 micrograms/ml) to the gastric segment produced similar degrees of vasodilation as observed with ethanol. The response to these vasodilators could be markedly attenuated with specific antagonists of these substances (histamine: pyrilamine plus cimetidine; adenosine: 8-phenyltheophylline). In our final experiments, indomethacin or histamine- or adenosine-receptor antagonists were given before application of topical ethanol. Indomethacin or histamine antagonists had no significant effect on the time course or magnitude of ethanol induced vasodilation. In contrast, pretreatment with 8-phenyltheophylline significantly reduced changes in vascular resistance during exposure to luminal ethanol. These results suggest that locally released adenosine is an important mediator of ethanol-induced vasodilation in the canine stomach under these conditions. PMID- 8476054 TI - Continuous measurement of rat gastric blood flow using Doppler flowmeter. AB - We describe the use of pulsed Doppler flowmetry to permit continuous measurement of gastric blood flow in the anesthetized rat. The aims of this study were: 1) to assess the stability of blood flow during Doppler flowmetry; 2) to assess the ability of Doppler flowmetry to record rapid, transient blood flow changes; and 3) to validate Doppler flowmetry against an established blood flow measurement technique using labeled microspheres. Measurements over 3-h periods with a Doppler probe placed on the left gastric artery showed that there was an initial 30-min stabilization period; after this the mean percentage coefficient of variation, indicating intraindividual variability for blood flow, was < 10% for the remaining 150 min. The infusion of norepinephrine produced rapid, transient blood flow changes, including the typical "autoregulatory escape" and "postinfusion hyperemia," both of which were detected by Doppler flowmetry. The accuracy of pulsed Doppler flowmetry in measuring gastric blood flow was established by the demonstration of a highly significant agreement between blood flow measured by the Doppler flowmetry and microsphere techniques. These data indicate that pulsed Doppler flowmetry is an accurate method for the continuous measurement of left gastric artery blood flow in the rat. PMID- 8476055 TI - Different relationships between cellular ATP and hepatic uptake among taurocholate, cholate, and organic anions. AB - Effects of cellular ATP content on uptake of cholate (CA) and organic anions (OAs; dibromosulfophthalein and benzylpenicillin) by isolated rat hepatocytes were investigated and were compared with that on taurocholate (TCA). Within 5 min of exposure to metabolic inhibitors (MIs), cellular ATP content fell to less than one-fifth of the control value, and the initial velocity of the total uptake of CA, Na(+)-independent uptake of CA and TCA, and the uptake of the OAs dropped in parallel with the decrease in cellular ATP. Whereas for the total uptake of TCA, the initial uptake remained virtually unchanged for a 5-min incubation with the MIs; a significant decrease in uptake was observed only after longer incubation times. Under variously ATP-decreased conditions, the initial velocity of the total uptake of CA and OAs was demonstrated to have a saturable relation to cellular ATP content, irrespective of exposure time to MIs. A difference in the Na(+)-dependent uptake of TCA and CA was also observed in terms of the inhibitory effect of the organic anion pravastatin. That is, the inhibition by pravastatin was partial for TCA uptake but almost complete for CA uptake. These findings suggest the following. 1) The mechanism of Na(+)-dependent CA uptake is different from that of TCA. 2) The Na(+)-independent uptake of bile acids and organic anions may be driven either by ATP hydrolysis (primary active transport) or by an as yet unidentified ion gradient that dissipates more rapidly than the Na+ gradient. PMID- 8476056 TI - Gastrin and CCK activate phospholipase C and stimulate pepsinogen release by interacting with two distinct receptors. AB - Both gastrin and cholecystokinin (CCK) can stimulate pepsinogen release from chief cells, but controversy exists about the receptors or intracellular mediators involved. In the present study, we prepared isolated chief cells from guinea pig stomach (> 90% pure) to investigate the ability of gastrin and CCK to alter cell function. The COOH-terminal octapeptide of CCK (CCK-8) caused an eightfold increase in pepsinogen release (EC50, 54 nM). Both CCK-8 and gastrin increased inositol phosphates, with CCK-8 (1 microM) and gastrin (3 microM) causing a 40- and 14-fold increase in [3H]IP1, 10- and 6-fold for [3H]IP2, and 8- and 4-fold for [3H]IP3. CCK-8 caused a half-maximal increase in [3H]IP3 at 2 nM, and the dose-response curve was monophasic, whereas with gastrin the curve was biphasic, with an EC50 of the initial component (20% maximal) at 38 nM and the second component at 10 microM. L-364,718 (0.1 microM) inhibited the secondary increase seen with gastrin concentrations > 10 nM. The CCK-A-selective agonist A 71378 was 85-90% as efficacious as CCK-8 and was equally potent. With 0.1 microM L-364,718, A-71378 caused no increase in [3H]inositol phosphates until > 10 nM, whereas CCK-8 caused 15% of maximal increase at concentrations > 0.3 nM. Similar results were obtained with cytosolic calcium measured using fura-2 or on CCK-8- or gastrin-stimulated pepsinogen release. These results demonstrate that gastrin and CCK-8 can alter chief cell function by interacting with either a CCK-A or CCK B/gastrin receptor. Both receptors are coupled to phospholipase C and cause changes in inositol phosphates, cytosolic calcium, and pepsinogen release; however, the intracellular amplification differs between the two receptor subtypes. Activation by CCK-related peptides of the CCK-A receptor subtype accounts for 85-90% of the maximal changes in cellular function, and activation of the CCK-B/gastrin receptor accounts for 10-20% of maximal changes. PMID- 8476057 TI - Downregulation of neutral endopeptidase (EC 3.4.24.11) in the inflamed rat intestine. AB - Intestinal inflammation induced by the nematode Trichinella spiralis is accompanied by increased intestinal concentrations of substance P, a mediator of inflammation and a stimulant of smooth muscle contraction, and by intestinal hypermotility. The expression of neutral endopeptidase (NEP), a cell surface enzyme that degrades substance P in the extracellular fluid, was examined in the inflamed intestine. NEP enzymatic activity, measured by a fluorometric assay, was reduced by 84-fold in jejunal mucosa-circular muscle and by 12-fold in jejunal longitudinal muscle-myenteric plexus within 6 days after infection with T. spiralis. The downregulation was unaffected by treatment with betamethasone and was still observed in athymic animals. NEP protein levels, examined by Western blotting, confirmed the loss of NEP from inflamed tissue. The specific activity for degradation of substance P was reduced by sixfold in jejunal mucosa-circular muscle and by twofold in jejunal longitudinal muscle-myenteric plexus of rats infected with T. spiralis compared with uninfected controls. Thus the downregulation of NEP resulted in reduced substance P degradation, which may contribute to functional abnormalities of the inflamed intestine. PMID- 8476058 TI - pH-dependent nonlysosomal proteolysis contributes to lethal anoxic injury of rat hepatocytes. AB - Our aim was to test the hypothesis that pH-dependent nonlysosomal proteolysis is a key mechanism culminating in lethal anoxic injury of rat hepatocytes. Although lysosomal proteolysis was suppressed during anoxia, total nonlysosomal proteolysis was increased twofold compared with aerobic controls. Extracellular acidosis inhibited total nonlysosomal proteolysis and improved cell survival during anoxia. Indeed, we found a direct highly significant linear relationship between cell death and total nonlysosomal proteolysis as modulated by changes in the extracellular pH (r = 0.99, P < 0.01). Glycolytic generation of ATP from fructose during anoxia suppressed total nonlysosomal proteolysis and improved cell survival. An increase in a pH-dependent calpain-like protease activity was also identified during anoxia, but calpain-like protease activity only accounted for 16% of total nonlysosomal protease activity. In addition, the calpain protease inhibitor Cbz-Leu-Leu-Tyr-CHN2 only partially protected against cell killing despite complete inhibition of calpain-like protease activity. These data suggest that pH-dependent total nonlysosomal proteolysis contributes to lethal cell injury during anoxia. However, calpain protease activity only partially contributes to total nonlysosomal protease activity and cell death. PMID- 8476059 TI - Asialoglycoprotein receptor mRNAs are expressed in most extrahepatic rat tissues during development. AB - The expression of an asialoglycoprotein receptor, comprised of a major (R-1) and minor (R-2/3) component, was characterized in various rat tissues during postnatal development. Two R-1 mRNA subspecies were identified in the liver by Northern blots. The 1.4-kb form, which was the predominant subspecies in the liver, was detected in small amounts only in the stomach and kidney. The 1.7-kb mRNA, however, was present in all extrahepatic tissues examined. R-1 mRNA content in the liver increased by only 38% during the suckling period, but the extrahepatic R-1 mRNA had a dramatic biphasic developmental pattern with the highest levels at birth and after weaning. The R-2/3 mRNA was present as a single species on Northern blot in the liver and in a restricted number of extrahepatic tissues (salivary glands, ileum, and kidney) but was detected in most tissues by polymerase chain reaction. The R-2/3 mRNA content in the liver increased fourfold after birth but was consistently low in the other tissues. [57Co]cobalamin haptocorrin binding activity was present in all extrahepatic tissues examined, although only at a level 2-5% of hepatic binding. Binding affinities of the adult kidney brush-border membranes (1.9 x 10(9) M-1) and the adult liver plasma membranes (2.4 x 10(9) M-1) were comparable. On Western blot, < 4% of adult liver R-1 content and a relatively larger amount of R-2/3 were detected in all four extrahepatic tissues examined. Thus the low binding activity in extrahepatic tissues correlates with the presence of both receptor subunits, which are closely related to or identical with the hepatic receptor subunits. PMID- 8476060 TI - Effects of autonomic antagonists and growth factors on activity-mediated hyperplasia of rat parotid. AB - Administration of the autonomic antagonists atropine (1 mg/kg body wt), propranolol (2 mg/kg body wt), and phenoxybenzamine (2 mg/kg body wt) before the dietary change from all liquid to solid chow prevented an increase in uptake of [3H]thymidine into DNA of rat parotid gland associated with this dietary change. Administration of either the cholinergic antagonist alone or the adrenergic antagonists alone produced partial inhibition. The effects of complete autonomic blockade were not reversed when nerve growth factor (NGF) or epidermal growth factor (EGF) was given immediately after administration of antagonists. The effects of complete autonomic blockade were similar to those seen with surgical removal of the autonomic nerves to the parotid. The increased levels of beta 1-4 galactosyltransferase seen with the dietary change were not evident in rats given both muscarinic and adrenergic antagonists before the change to solid food nor did NGF or EGF reverse these inhibitory effects. Histological observation showed that the surgically denervated gland was morphologically less homogenous than the gland of rats given the antagonists and had infiltrating connective tissue. Nonetheless, with the reduced acinar cell pool, the [3H]thymidine uptake of the denervated parotid and that of antagonist-injected animals was similar. PMID- 8476061 TI - Hepatic intracellular pH during the prereplicative period following partial hepatectomy. AB - To investigate the hypothesis that the regenerating liver undergoes intracellular alkalinization during the prereplicative period, we measured intracellular pH (pHi) after partial hepatectomy in the rat. pHi was studied in livers from female Wistar rats perfused in situ with buffer containing HCO3-/CO2. The multiple indicator-dilution technique was used to determine pHi from the distribution volume of dimethyloxazolidine-2,4-dione (DMO). Perfusion conditions influenced pHi. There was a curvilinear relationship between pHi and flow rate and a linear relationship between pHi and temperature. Under equivalent perfusion conditions there were no significant differences between pHi in normal livers (7.27 +/- 0.02) and that following partial hepatectomy (7.27 +/- 0.03 at 0 h, 7.27 +/- 0.04 at 4 h, 7.28 +/- 0.03 at 8 h, and 7.31 +/- 0.02 at 24 h) or sham surgery (7.27 +/ 0.04 at 4 h, 7.33 +/- 0.08 at 24 h). Therefore intracellular alkalinization does not occur following partial hepatectomy and is unlikely to be a signal for regeneration. PMID- 8476062 TI - Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia. AB - The hypothesis that complement factors may be involved in the postischemic activation of Kupffer cells (KC) and polymorphonuclear neutrophils (PMN) was investigated in a model of hepatic ischemia (45 min) and reperfusion in male Fischer rats in vivo. Depletion of serum complement before ischemia resulted in a significant attenuation of the KC-induced oxidant stress (enhanced oxidation of plasma glutathione) and also prevented the accumulation of PMNs in the liver during the initial reperfusion period of 1 h. Complement activation through injection of cobra venom factor (CVF; 75 micrograms CVF/kg) also induced enhanced oxidation of plasma glutathione and accumulation of PMNs in the liver. Isolation of KC and PMNs from the liver 1 h after CVF treatment demonstrated a similar priming effect for stimulation with phorbol myristate acetate and opsonized zymosan as was observed in the postischemic liver. Complement-depleted animals and animals pretreated with the soluble human complement receptor type 1 (BRL 55730; 22.5 mg/kg) accumulated significantly less PMNs in the postischemic livers during longer reperfusion periods (24 h) and sustained significantly less injury. It is concluded that complement is involved in the induction of a KC-induced oxidant stress, the priming of KC and PMNs for enhanced reactive oxygen generation, and the continuous accumulation of PMNs in the liver during reperfusion. PMID- 8476063 TI - Adenine nucleotide degradation in ischemic rabbit lung tissue. AB - The aim of the study was to determine the pathways and site of adenosine triphosphate (ATP) catabolism during lung ischemia, which thus far are largely unknown. For this purpose we used the isolated rabbit lung. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 ml/kg), the deflated heart lung blocks were isolated, immersed in saline solution, and stored at 37 degrees C. In group I (normothermic ischemia; n = 6) tissue content of ATP decreased progressively from 9.42 +/- 0.58 mumol/g dry wt to 3.42 +/- 0.24 mumol/g dry wt after 30 min of ischemia and further to 0.51 mumol/g dry weight after 4 h. Hypoxanthine was the major catabolite (92% of the nucleoside and purine base fraction at 4 h ischemia). Adenosine did not accumulate (preischemic 0.08 +/- 0.02 mumol/g dry weight vs. 0.13 +/- 0.01 mumol/g dry weight; P > 0.05). AMP accumulated, but also inosine monophosphate (IMP), which was undetectable before ischemia, increased significantly during ischemia. To determine the breakdown pathway of AMP, 400 microM of the adenosine deaminase inhibitor EHNA was added to the flush solution in group II (n = 6). During ischemia, ATP breakdown was unaltered but adenosine became the major catabolite (2.8 times the concentration of hypoxanthine at 4 h ischemia). By pretreatment of the rabbits with the nucleoside transport inhibitor R 75231 (group III; n = 6) no effect was observed on the concentrations during ischemia of inosine and hypoxanthine and only a minor increase of adenosine was found. Cytochemical localization of nucleoside phosphorylase revealed activity predominantly in the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476064 TI - Effects of gastrin-releasing peptide and analogues on guinea pig nasal mucosal secretion. AB - The effects of gastrin-releasing peptide (GRP), bombesin, GRP-(1-16) and GRP-(21 27) on guinea pig nasal mucosal secretion were studied in vivo. GRP, bombesin, and GRP-(21-27) induced significant secretion of total protein, albumin, and alkaline phosphatase. GRP induced significant secretion at lower concentrations (10(-11) and 10(-10) M) than were required for bombesin and GRP-(21-27) (10(-7) M). GRP-(1-16) did not stimulate secretion, indicating that the COOH-terminal region of GRP contained the secretagogic principle. Capsaicin, a stimulant of nociceptive sensory nerves, stimulated GRP release into nasal secretions. These data suggest that GRP is present in guinea pig nasal mucosa and that the COOH terminal region of GRP may regulate mucosal macromolecule secretion. PMID- 8476065 TI - Characterization of L-arginine transport by pulmonary artery endothelial cells. AB - The transport of L-arginine by porcine pulmonary artery endothelial cells (PAECs) was characterized. Uptake of 50 microM L-arginine was time dependent and linear in the presence and absence of sodium, with approximately 70% of uptake occurring via a carrier-mediated Na(+)-independent process. Kinetic studies of saturable Na(+)-independent transport revealed two transport components: a high-affinity transporter [Michaelis constant (Km) = 304 +/- 23 microM, maximal transport velocity (Vmax) = 679 +/- 34 pmol.mg protein-1.30 s-1], and a low-affinity carrier (Km = 3.9 +/- 1.0 mM, Vmax = 2.8 +/- 0.7 nmol/mg protein-1.30 s-1). Saturable Na(+)-independent uptake of 50 microM L-arginine transport showed no significant variation in uptake between pH 6.0 and 8.0 and was blocked by the system y+ substrates L-arginine, L-homoarginine, L-lysine, and L-ornithine. Na(+) dependent L-arginine transport occurred via a single high-affinity system (Km = 62 +/- 3 microM, Vmax = 211 +/- 24 pmol.mg protein-1.30 s-1) which was significantly inhibited by L-arginine, L-lysine, L-ornithine, L-leucine, L alanine, L-cysteine, and L-glutamine, but not by 2-methylaminoisobutyric acid. Na(+)-dependent arginine uptake was pH and hormone insensitive, and lithium did not substitute effectively for sodium. These data are consistent with mediation of high-affinity arginine transport by PAECs via Na(+)-independent system y+ and Na(+)-dependent system BO,+. PMID- 8476066 TI - Cu,Zn superoxide dismutase in vascular cells: changes during cell cycling and exposure to hyperoxia. AB - Conditions that generate reactive oxygen species elevate Cu,Zn superoxidase dismutase (SOD) in endothelial cells (EC) concomitant with decreased cellular proliferation. The current studies were undertaken with both vascular EC and smooth muscle cells (SMC) to compare the influences of cellular proliferation with those of hyperoxia on induction of Cu,Zn SOD. To assess cell cycling alone, EC and SMC were growth arrested, then released from arrest. Cell cycling was monitored by [3H]thymidine incorporation, counts, and flow cytometry. SOD catalytic activity was measured spectrophotometrically and SOD protein by enzyme linked immunosorbent assay. A digoxigenin-labeled probe was used to quantify SOD mRNA by Northern analysis. EC reached the S phase of the cell cycle in 18 h and completed one cycle in 24-30 h, whereas SMC took 24-30 h to reach the S phase and 48 h to complete one cycle. Cu,Zn SOD mRNA for both EC and SMC was very low during the Go/G1 phase, peaked during the S phase, and then reverted to lower values as cells progressed through their cycles. Cu,Zn SOD activity and immunoprotein content showed corresponding changes to those of mRNA. Exposure to hyperoxia (95% O2) delayed the entry of released cells into the S phase of the cell cycle and blocked the cells in the S or G2 phase, but induced Cu,Zn SOD mRNA before the S phase and caused persistence of elevation of Cu,Zn SOD mRNA as cells progressed through their cycles. Exposure to hyperoxia also induced Cu,Zn SOD mRNA in growth-arrested cells within 24-48 h. Thus our studies support roles for both cells cycle dependency and reactive oxygen species in the induction of Cu,Zn SOD. PMID- 8476067 TI - Hydraulic conductivity of ischemic pulmonary venules. AB - We report the first determination of lung endothelial barrier properties in ischemic, nonreperfused microvessels. We quantified the endothelial barrier in terms of hydraulic conductivity (Lp) in single pulmonary venules (diameter 20-50 microns) of isolated blood perfused lungs (dog, rat), held at constant inflation pressure (5 cmH2O) with a gas mixture containing 21% oxygen. Lp were determined by our split-drop technique in which an oil drop is first microinjected into a venule and then split by microinjection of a protein solution. Lp was interpreted from measurements of the rate of oil drop movement. Baseline Lp recorded in the first 30 min of perfusion averaged 3.4 +/- 0.9 x 10(-7) ml/(cm2.s.cmH2O). Then, in two separate groups of venules in which we established 1.3 +/- 0.1 h and 3.4 +/- 0.8 h of ischemia, we determined Lp which were, respectively, 145 +/- 6.5 and 308 +/- 13% above baseline (P < 0.05). We conclude that ischemia alone, in the absence of reperfusion, significantly deteriorates the lung endothelial barrier. PMID- 8476068 TI - Cell surface carbohydrates modulate neutrophil adherence to alveolar type II cells in vitro. AB - We characterized the influence of phosphorylated sugars and cell surface sialic acids on the adherence of human polymorphonuclear leukocyte (PMN) to rat alveolar type II cell (ATII cells) and human-derived A549 cell monolayers in vitro. Percent adherence of radiolabeled polymorphonuclear leukocytes was assessed after incubating cells with the carbohydrates, enzymes, or lectins to be tested. Lactose-1-phosphate (Lact1P) and maltose-1-phosphate (Malt1P) (10 mM) inhibited adherence of PMN to ATII cells and A549 cells. Maximal inhibition followed treatment of both PMN and rat ATII cells and amounted to 85 +/- 7% with Lact1P and 92 +/- 3% with Malt1P. Inhibition was concentration dependent. Incubation of PMN with mannose-6-phosphate reduced adherence to rat ATII cells and A549 cells by 36 +/- 11 and 39 +/- 8%, respectively. Maximal concentrations of sugars did not alter cellular viability. Neuraminidase-induced desialilation of ATII cells increased adherence of PMN by 36 +/- 7% to rat ATII cells and by 86 +/- 18% to A549 cells. Masking of terminal sialic acids on rat ATH cells with Limulus polyphemus agglutinin (100 micrograms/ml) increased adherence by 50 +/- 2%. These results indicate that cell surface carbohydrates are involved in the regulation of the adhesive interaction between PMN and ATII cells in vitro. PMID- 8476069 TI - Interleukin-8: an important chemoattractant in sputum of patients with chronic inflammatory airway diseases. AB - Sputum from patients with cystic fibrosis, bronchiectasis, and chronic bronchitis contains neutrophils and neutrophil proteases, which have been implicated in the pathophysiology of mucus hypersecretion in airways. We asked whether interleukin 8 (IL-8), a potent neutrophil chemoattractant, might be involved in recruiting neutrophils into airways of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis. We found significant neutrophil chemotactic activity in sputum obtained from these patients. The IL-8 concentrations that we measured in sputum of patients with cystic fibrosis (7.1 +/- 1.0 x 10(-9) M, mean +/- SE), bronchiectasis (9.6 +/- 2.9 x 10(-9) M), and chronic bronchitis (2.8 +/- 1.0 x 10(-9) M) have been reported to cause significant chemotaxis in vitro and in airways in vivo, whereas concentrations measured in induced sputum from healthy subjects (1.1 +/- 0.3 x 10(-10) M) do not. A monoclonal antibody to IL-8 significantly inhibited the chemotactic activity in patients' sputum by 75-98%, but not in induced sputum from healthy subjects (9%). We conclude that IL-8 is an important chemotactic factor in sputum of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis, and we suggest that IL-8 accounts, at least in part, for neutrophil recruitment into airways of patients with these diseases. PMID- 8476070 TI - Pulmonary surfactant protein A stimulates chemotaxis of alveolar macrophage. AB - Pulmonary surfactant modulates several functions of alveolar macrophages including phagocytosis, killing, and chemotaxis. We hypothesized that the reported stimulatory effect of surfactant on macrophage migration was mediated by one of the surfactant proteins, SP-A. We found that macrophage migration was stimulated by SP-A in a concentration-dependent manner. A concentration of 105 micrograms SP-A/ml enhanced migration approximately 10-fold. Heat treatment or reduction and alkylation of SP-A reduced its stimulatory effect. A checker-board analysis showed that SP-A stimulated migration primarily by enhancing chemotaxis (directed movement) rather than chemokinesis (random movement). The interaction of SP-A with macrophages may be mediated at least partly by the collagen-like domain of SP-A. We speculate that SP-A may play a multifunctional role in regulating pulmonary immune response by stimulating multiple macrophage functions. PMID- 8476071 TI - Cholesterol, macrophages, and gene expression of TGF-beta 1 and fibronectin during nephrosis. AB - Hypercholesterolemia aggravates experimental progressive glomerular injury. Evidence suggests the infiltrating glomerular macrophage (M phi) is a potential effector mechanism for the noxious effects of hypercholesterolemia. Because transforming growth factor (TGF)-beta 1 is secreted by activated M phi s and also stimulates fibronectin production by glomerular cells, we evaluated the kinetics of gene expression for these moieties in glomeruli isolated from nephrotic rats at 3, 7, 11, and 42 days after the delivery of puromycin aminonucleoside (PA). We also assessed whether cholesterol feeding, which raises the glomerular M phi number, alters the glomerular mRNA levels for TGF-beta 1 and fibronectin. Glomerular mRNA levels for TGF-beta 1 and fibronectin in nephrotic rats exhibited a biphasic temporal pattern, decreasing significantly below control at 3 and 7 days after PA but increasing significantly at 11 and 42 days after PA. The upregulated gene expression for TGF-beta 1 and fibronectin at 11 days after PA temporally corresponded to the phase of mesangial M phi infiltration in this model. Cholesterol feeding to both normal and nephrotic rats significantly increased glomerular TGF-beta 1 and fibronectin mRNA levels at 11 days after PA. Immunohistochemical labeling for M phi s and intracellular TGF-beta 1 demonstrated both mesangial and cortical interstitial localization with the TGF beta1-positive cells possessing M phi nuclear morphology. These findings identify a novel interaction between hypercholesterolemia, augmented glomerular M phi accumulation, and upregulated glomerular TGF-beta 1 and fibronectin gene expression. These perturbations within the acutely injured glomerulus constitute an early pathobiological determinant for the later development of mesangial matrix expansion and glomerulosclerosis. PMID- 8476072 TI - Urea induces Egr-1 and c-fos expression in renal epithelial cells. AB - The membrane-permeant solute urea, in concentrations present in the mammalian renal medulla, increased expression at the mRNA level of two immediate-early gene (IEG) transcription factors, Egr-1 and c-fos, in a time- and dose-dependent fashion in confluent growth-suppressed Madin-Darby canine kidney (MDCK) cells. This upregulation occurred in the absence of both cytotoxicity and an inhibition of protein synthesis, two potential nonspecific inducers of IEG expression. These findings were of interest because we have previously shown that hyperosmotic stress induced by the functionally membrane-impermeant solute NaCl increased expression of these IEG, whereas hyperosmotic stress induced by the membrane permeant solute glycerol failed to do so. The urea-induced increase in Egr-1 mRNA expression was not secondary to enhanced message stability as determined by actinomycin D experiments and is therefore likely a consequence of urea-induced transcriptional activation. Augmented Egr-1 expression in response to urea treatment was also observed in another renal epithelial cell line, LLC-PK1, but not in other cell types examined. Therefore cells of renal epithelial origin may be uniquely capable of responding to hyperosmotic urea with increased expression of IEG transcription factors, and this increase is likely transcriptionally mediated. PMID- 8476073 TI - Urea selectively induces DNA synthesis in renal epithelial cells. AB - Hyperosmotic stress with the functionally impermeant solute NaCl has been shown by us and others to inhibit cell growth and DNA synthesis. Several lines of evidence suggest that urea, the other principal renal medullary solute, may exert a growth-promoting effect on renal epithelial cells. Among these is the finding that urea upregulates expression at the mRNA level of two growth-associated immediate-early genes, Egr-1 and c-fos. In the present study, urea, in concentrations characteristic of the renal medulla, increased [3H]thymidine incorporation approximately threefold in confluent, growth-suppressed Madin-Darby canine kidney (MDCK) cells, whereas another readily membrane-permeant solute, glycerol, did not. Urea also overcame the inhibitory effect of hyperosmotic NaCl on DNA synthesis. The urea-induced increase in [3H]thymidine incorporation was also evident in the renal epithelial LLC-PK1 cell line, but not in renal nonepithelial and epithelial nonrenal cell types examined. In addition, it was associated with a 15% increase in total DNA content measured fluorometrically at 24 h of treatment. There was, however, no associated increase in cell proliferation as measured by cell number, total protein content, or cell cycle distribution. Urea also failed to induce polyploidy or aneuploidy. Therefore cells of renal epithelial origin may be uniquely capable of responding to hyperosmotic urea with increased DNA synthesis through an undefined and potentially novel mechanism. PMID- 8476074 TI - Effects of anemia on morphology of rat renal cortex. AB - Information on morphological and functional effects of anemia in kidney is scarce, although this organ plays a major role in erythropoietin production, which is strongly stimulated in anemia. We undertook a morphological study of kidneys of anemic rats. Anemia was induced by X-irradiation and subsequent injection of a hemolytic drug. The most striking effects of anemia on renal morphology were damages in the proximal tubule and a volume increase of the peritubular space. These effects were evident only in the cortical labyrinth. Morphometry showed that the enlargement of the peritubular space reflected an increase of the volumes of both capillaries and interstitium. The structural changes in the cortical interstitium were associated with increased activity of the ecto-5'-nucleotidase in the fibroblasts. We suggest that hypoxia accounts for most of the observed alterations. The hypoxic proximal tubule might release the nucleotide AMP, which would be hydrolyzed to adenosine by the ecto-5' nucleotidase in the interstitium. Adenosine has been reported to trigger the synthesis of erythropoietin and the growth of blood capillaries. PMID- 8476075 TI - Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells. AB - The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes. PMID- 8476076 TI - Sex differences in control of renal outer medullary circulation in rats: role of prostaglandins. AB - A calibration technique was developed to quantify blood flow changes in the renal cortex and outer medulla in rats using platinum needle electrodes sensing partial pressure of locally generated hydrogen. Measurements were made in male and female rats to investigate sex differences in the humoral control and autoregulation of regional renal circulations. In males, both cortical and outer medullary blood flows were efficiently auto-regulated above an arterial pressure of 100 mmHg. The converting-enzyme inhibitor quinapril increased blood flow by 20% in both kidney zones, and inhibition of prostaglandin synthesis by indomethacin did not change the flow. In females, similar results were obtained only for the cortex; the medulla had a different response pattern. The blood flow was not autoregulated in the experimental pressure range up to 120 mmHg; quinapril did not change the flow, but indomethacin decreased the flow by 16% and at the same time restored its autoregulation capacity. We conclude that: 1) the medulla of female rats has a high basal level of vasodilator prostaglandins, which interferes with blood flow autoregulation in this kidney area, and 2) medullary flow in female rats is little affected by endogenous angiotensin. PMID- 8476077 TI - Maintenance of endothelin-induced renal arteriolar constriction in rats is cyclooxygenase dependent. AB - Influence of arachidonate cyclooxygenase (COX) products on endothelin (ET)-evoked renal vasoconstriction was assessed. In microperfused rat afferent (AA) and efferent arterioles (EA), indomethacin had no effects on the maximal contraction of both AA and EA by ET, but reduced the duration of ET-induced constriction in both arterioles. ET infusion to rats in vivo resulted in a selective increase in efferent but not afferent arteriolar resistance, leading to a dramatic increase in transcapillary hydraulic pressure difference. Glomerular filtration rate (GFR), which fell progressively during infusion of ET alone, was markedly preserved by COX inhibition, but not during selective thromboxane A2 antagonism. In isolated glomeruli, release of prostaglandin (PG) F2 alpha in response to 10( 6) mol/l ET exceeded that the PGE2 by a ratio of 3.2. Collectively, these data provide strong evidence that locally released COX products, possibly PGF2 alpha, play a key role in sustaining ET-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without affecting EA constriction in vivo, thereby resulting in a dramatic reversal of the effects of ET on GFR. PMID- 8476078 TI - Effect of hyperosmolality on production and mRNA expression of ET-1 in inner medullary collecting duct. AB - The effects of hyperosmolality on the production and mRNA expression of endothelin-1 (ET-1) in inner medullary collecting duct (IMCD) were examined in the present study. Osmolality in incubation media was changed from 290 to 490 or 690 mosmol/kgH2O by adding NaCl, urea, mannitol, or raffinose. A preliminary experiment was carried out using tubule suspension from the inner medulla. Hyperosmolality by NaCl stimulated ET-1 accumulation in rats (from 323.5 +/- 76.3 to 478.0 +/- 108.4 and 573.7 +/- 47.8 pg.mg protein-1 x 24 h-1 in 290, 490, and 690 mosmol/kgH2O, respectively) and rabbits. In contrast, hyperosmolality by urea markedly decreased ET-1 accumulation and hyperosmolality by mannitol showed no effect on it. We next examined whether hyperosmolality changes ET-1 mRNA. After incubation in isotonic or hypertonic solution for 6 h, ET-1 mRNA was determined using reverse transcription and polymerase chain reaction (PCR) in microdissected IMCD and glomerulus. Hyperosmolality by NaCl and raffinose significantly increased the PCR products of ET-1 mRNA in IMCD, whereas mannitol did not. The stimulatory effect of hyperosmolality by NaCl on ET-1 mRNA expression was not observed in glomerulus. Our data suggested a stimulatory effect of hyperosmolality on production and mRNA expression of ET-1 in IMCD but not in glomerulus. PMID- 8476079 TI - Effect of phosphorus restriction on renal response to oral and intravenous protein loads in rats. AB - Dietary phosphorus restriction ameliorates renal injury in rats. This may be due to changes in renal hemodynamics, including those factors associated with protein induced hyperfiltration. To test this, we measured inulin clearance (CIn), p aminohippuric acid clearance (CPAH), mean arterial blood pressure, and renal vascular resistance (RVR) 1 h before and 100 min after either oral gavage of 2 g bovine serum albumin or intravenous infusion of 5% glycine in female Sprague Dawley rats previously fed for 3-8 wk a 0.5% or a 0.1% phosphorus diet. Baseline CIn, CPAH, blood pressure, and RVR were similar. After albumin gavage, CIn rose 20% (P < 0.01) for the 0.5% phosphorus group but did not change for rats fed the 0.1% phosphorus diet. Other measured parameters, including plasma glucagon and renin activity, were not influenced by dietary phosphorus content. In contrast, during intravenous infusion of glycine, hyperfiltration was induced in phosphorus restricted rats. Thus dietary phosphorus restriction ablates oral protein but not intravenous amino acid-induced hyperfiltration, suggesting a gut-mediated mechanism for the former. These data highlight the potential importance of dietary phosphorus as a mediator of renal hemodynamics. PMID- 8476080 TI - Prostanoids promote pial arteriolar dilation and mask constriction to oxytocin in piglets. AB - We determined effects of oxytocin on piglet pial arterioles and the role of prostanoids in mediating arteriolar responses. Anesthetized piglets were equipped with closed cranial windows, and arteriolar diameter was measured using intravital microscopy. Pial arterioles were exposed to 10(-10) to 10(-4) M oxytocin. Cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2) and 6 ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were determined using radioimmunoassay. Baseline diameter was 110 +/- 4 microns and increased to 120 +/ 6 microns at 10(-8) M (9 +/- 3%, n = 20). CSF levels of PGE2 were 697 pg/ml during baseline and increased to 1,685 +/- 316 pg/ml during 10(-6) M, 2,243 +/- 327 pg/ml during 10(-5) M, and 2,941 +/- 500 pg/ml during 10(-4) (n = 6). CSF levels of 6-keto-PGF1 alpha were 354 +/- 73 pg/ml during baseline and increased to 734 +/- 168 pg/ml at 10(-5) M and to 836 +/- 167 pg/ml at 10(-4) M (n = 5). After inhibition of prostaglandin synthesis by indomethacin (5 mg/kg i.v.), oxytocin constricted at all doses, starting at 10(-10) M (5 +/- 2%) and continuing to constrict at 10(-4) M (24 +/- 2%, n = 14). We conclude that: 1) piglet pial arterioles respond to relatively low levels of oxytocin, 2) local presence and/or production of prostanoids promotes dilation, and 3) endogenous prostanoids prevent constriction of pial arterioles to oxytocin. Our results suggest that oxytocin could play a role in the regulation of cerebral hemodynamics. PMID- 8476081 TI - Initiation of cardiac hypertrophy in response to thyroxine is not limited by age. AB - We examined the role of age in the initiation of thyroxine-induced (T4) cardiac hypertrophy. T4 (0.4 mg/kg sc) was administered to prepubescent (2 mo), young adult (6 mo), and senescent (24 mo) Fischer 344 rats for 4 days. While significant increases in left ventricular (LV) mass and RNA/LV were evident at 4 days in all T4-treated groups, the elevation in RNA/LV occurred earlier (2 days) in the senescent group. A 0.2-mg/kg dose of T4 elevated RNA values within 24 h in senescent, but not in prepubescent, rats. LV norepinephrine levels were measured to determine whether it plays a role in this model of cardiac hypertrophy. When synthesis of this catecholamine was blocked with alpha-methyl-p-tyrosine, tissue levels fell significantly in all groups, and the decrement was similar in T4 treated and control rats in the two younger groups. We conclude that: 1) the initiation of T4-induced cardiac hypertrophy is not compromised in senescent rats, 2) hearts of senescent rats respond earlier and to a lower dose of T4 than young rats, and 3) the cardiac hypertrophy that occurs in hyperthyroidism is not due to enhanced levels of available cardiac norepinephrine. PMID- 8476082 TI - Effect of residual stress on transmural sarcomere length distributions in rat left ventricle. AB - It has been previously shown that the myocardium in the walls of the unloaded passive left ventricle (LV) is not stress free. To assess the functional significance of residual stress in the ventricular wall, we compared the transmural distributions of sarcomere length (SL) in specimens of rat LV myocardium fixed in the unloaded (residually stressed) and stress-free states. When a cross-sectional ring cut from the equatorial region of the freshly arrested rat hearts was cut radially to relieve residual stress, it sprang open into an arc with a mean opening angle of 45 +/- 15 degrees (SD) (n = 8). During immersion fixation in glutaraldehyde, the opening angle increased 9.3 +/- 7.1 degrees (SD) overall. SLs were measured at 16 equally spaced transmural locations from the free wall in the stress-free tissue sections and were compared with control measurements from adjacent cross-sectional rings in which residual stress had not been relieved. Average SL for the stress-free tissue (n = 11) was 1.84 +/ 0.05 (SD) microns and for the unloaded tissue was 1.83 +/- 0.06 (SD) microns. However, analysis of covariance on the pooled data showed that the transmural distributions were significantly different (P < 0.0001). Whereas SL was uniform across the wall in the stress-free state with a mean gradient of -0.014 +/- 0.044 (SD) microns/total wall thickness, there was a significant decrease (P = 0.001) in SL from epicardium to endocardium in the intact unloaded tissue [slope = 0.114 +/- 0.054 (SD) microns/total wall thickness].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476083 TI - Effects of neurotensin and neuropeptide Y on coronary circulation and myocardial function in dogs. AB - This study analyzed the effects of the neuropeptides, neurotensin, and human and porcine analogue, neuropeptide Y, in anesthetized open-chest dogs. The left anterior descending coronary artery was cannulated and perfused at constant pressure via a blood reservoir. Flow to the coronary cannula was measured by an electromagnetic flowmeter, and regional segment lengths were measured by sonomicrometer crystals. Neurotensin injected into the coronary cannula resulted in a dose-dependent increase of coronary flow; neuropeptide Y resulted in a decrease of coronary flow. Because these changes in flow were not explained by systemic hemodynamic effects or alterations in regional myocardial function, they were considered to be coronary dilatation or constriction. Coronary dilatation by neurotensin was not prevented by alpha- or beta-adrenoceptor blockade but was completely abolished by indomethacin or by lowering coronary perfusion pressure to 35 mmHg when depressed systolic segment shortening indicated myocardial ischemia. Coronary constriction by neuropeptides Y persisted at coronary perfusion pressure of 35 mmHg and was only attenuated by indomethacin. We conclude that in contrast to systemic effects, coronary vasodilatation by neurotensin is mediated by a prostanoid product of cyclooxygenase. Preactivation of the prostaglandin system may explain why neurotensin lost its coronary dilator effect during myocardial ischemia. Neuropeptide Y may elicit coronary constriction in addition to mechanic reduction of coronary flow resembling severe coronary stenosis. PMID- 8476084 TI - Cerebral blood flow responsivity to CO2 in anesthetized chronically diabetic dogs. AB - The effect of diabetes mellitus on the cerebrovascular response to CO2 is unclear. We examined the effects of diabetes on cerebral blood flow (CBF) and cerebral oxygen uptake (CMRO2) during CO2 alterations. Four groups of dogs were studied: nondiabetic, normoglycemic controls; non-diabetic acute hyperglycemia; diabetic (pancreatectomy) with high-dose insulin treatment to maintain blood glucose between 4.0 and 6.0 mM; and diabetic with low-dose insulin treatment to maintain blood glucose at 13.2 +/- 0.4 mM. Six weeks after either sham surgery or pancreatectomy, dogs were anesthetized with fentanyl (50 micrograms/kg) plus pentobarbital (10 mg/kg), and microsphere determinations of CBF were made during normo-, hypo-, and hypercapnia. On the day of the study, arterial glucose levels in the control, acute hyperglycemia, and high- and low-dose insulin diabetic groups were 4.0 +/- 0.3, 14.9 +/- 2.5, 3.3 +/- 0.8, and 13.3 +/- 0.7 mM, respectively, at control. The corresponding baseline CMRO2 levels were 2.8 +/- 0.2, 3.0 +/- 0.2, 4.1 +/- 0.4, and 4.0 +/- 0.3 ml O2.100 g-1 x min,1, and the values in both diabetic groups were higher than control. Normocapnic CBF in the acute hyperglycemia, high-dose insulin, and low-dose insulin groups was elevated from control (54 +/- 3, 50 +/- 3, 51 +/- 3 vs. 36 +/- 1 ml x 100 g-1 x min-1) and cerebrovascular resistance was lower (2.24 +/- 0.15, 2.51 +/- 0.14, 2.38 +/- 0.21 vs. 3.35 +/- 0.18 mmHg.ml-1 x 100 g.min). CBF responses to both hypercapnia and hypocapnia were similar among groups. Thus both acute hyperglycemia and diabetes decrease cerebrovascular resistance and increase CBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476085 TI - Effects of atrial fibrillation on left and right atrial dimensions, pressures, and compliances. AB - The effects of atrial fibrillation on left and right atrial dimensions, pressures, and compliances were examined in two groups of seven barbiturate anesthetized open-chest pigs. Atrial diameters and pressures were recorded during atrioventricular (AV) pace and thereafter during atrial fibrillation. Both rhythms were studied with constant ventricular rate after complete AV block. Left atrial maximal diameter, which appeared at the end of the atrial filling phase, decreased from 32.4 (28.9-36.7; median and 95% confidence interval) to 31.3 (28.4 35.7) mm after induction of atrial fibrillation. The right atrial maximal diameter also decreased, although not significantly. Atrial pressure at the peak of the v wave rose from 7.0 (5.5-8.5) to 9.6 (8.3-11.2) mmHg in the left atrium and from 5.0 (4.3-5.6) to 7.3 (6.2-8.7) mmHg in the right atrium. Left and right atrial chamber stiffness constants increased from 0.25 (0.19-0.48) to 0.41 (0.28 0.66) mm-1 and from 0.21 (0.11-0.31) to 0.33 (0.30-0.39) mm-1, respectively. Instantaneous diastolic atrial compliance decreased in both atria after induction of atrial fibrillation. Thus, during atrial fibrillation with regular ventricular rate, changes in atrial diameter, pressure, and compliance take place. PMID- 8476086 TI - Fluorescent properties of rat cardiac trabeculae microinjected with fura-2 salt. AB - We have measured force, sarcomere length, and Ca2+ during twitches in rat cardiac trabeculae. To avoid the difficulties associated with fura-2/acetoxymethyl ester (AM), fura-2 salt was iontophoretically microinjected into the preparation using a single impalement site; this is possible because fura-2 diffuses through the gap junctions between cells. By use of this method, the estimated peak of the [Ca2+] transient during a twitch was not statistically different at different sarcomere lengths: 875 +/- 92 nM at a sarcomere length of 2.15 microns vs. 905 +/ 67 nM at a sarcomere length of 1.65 microns (means +/- SD, n = 10). When trabeculae were loaded using fura-2/AM, the estimated peak of the [Ca2+] transient at a sarcomere length of 2.15 microns was 540 +/- 180 nM (means +/- SD, n = 5). The time course of the Ca2+ transients at different sarcomere lengths is qualitatively similar, but small systematic differences were observed during the relaxation period. On the other hand, the duration of twitch force increases dramatically as the muscle length is increased. As a result, when the trabeculae were held at short muscle lengths, the temporal relationship between force and the Ca2+ transient resembled the relationship between cell shortening and the Ca2+ transient measured in isolated myocytes. At longer lengths the temporal relationship between force and the Ca2+ transient more closely resembles that obtained in papillary muscles using aequorin. PMID- 8476087 TI - Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats. AB - To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition. PMID- 8476088 TI - Arteriolar endothelium-dependent vasodilation occurs during endotoxin shock. AB - Endotoxin shock has been reported to alter endothelial structure as well as function of large arteries from in vitro experiments. Cremaster muscle arteriolar dilator reactivity of pentobarbital-anesthetized rats was determined by videomicroscopy at control and 30, 90, 150, and 210 min after intravenous infusion of Escherichia coli endotoxin (6 mg/kg, 1-h period). The dilator response was tested by intra-arterial injections of 90 ng acetylcholine (ACh). At control A1, A2, and A3 arterioles dilated 45, 21, and 34%, respectively. Postendotoxin arterial pressure decreased progressively, the A1 arterioles constricted (P < 0.05), A2 diameters were unchanged and A3 diameters increased. Postendotoxin ACh dilations averaged 28, 23, and 25%. A1 dilation was significantly (P < 0.05) less than at control. Methylene blue (2.5 mg ia) attenuated the ACh response at control, but after endotoxin an intense downstream vasoconstriction resulted in stasis and reduced survival time occurred. Hydroquinone (HQ) partially blocked the responses to ACh postendotoxin. HQ significantly increased the survival time postendotoxin. It is evident postendotoxin that the endothelia of arterioles are functional and able to release nitric oxide (NO) throughout the entire survival period. The microvascular release of NO and the dilation response to ACh were substantially attenuated by methylene blue and HQ. The latter may block the more lethal effects of the inducible NO synthase. PMID- 8476089 TI - Effects of corticotropin-releasing factor on isolated rat heart activity. AB - We investigated effects of bolus administration of corticotropin-releasing factor (CRF) on parameters of cardiac activity in isolated working rat hearts. Effects at a dose of 5 micrograms of CRF were compared in hearts perfused with Krebs Henseleit solution, norepinephrine (NE, 10(-9) M), propranolol (3 x 10(-6) M), NG nitro-L-arginine (L-NNA, 3 x 10(-5) M), or indomethacin (3 x 10(-5) M). CRF increased coronary flow for > 30 min (P < 0.01) with maximum increases of 31.7%, suggesting a prolonged vasodilatory action of the peptide. CRF, in addition, induced transient (lasting < 10 min) increases in maximum aortic pressure and oxygen consumption (P < 0.01), suggesting an inotropic action of the peptide. Perfusions of NE and propranolol did not change the cardiac response to CRF. L NNA, inhibiting release of endothelium-derived relaxant factor (EDRF), and indomethacin diminished the vasodilatory response to CRF, as indicated by significantly shortened increases in coronary flow after CRF (P < 0.05). Indomethacin also enhanced peak increases in maximum aortic pressure after CRF (P < 0.01). The data confirm direct effects of CRF on cardiac activity. They also suggest that the mediation of coronary vasodilation by CRF involves the endothelial release of prostacyclin and EDRF. PMID- 8476090 TI - Recovery of myocardial function after repetitive episodes of reversible ischemia. AB - The question of whether recovery of regional myocardial function after repetitive, reversible ischemia differs from recovery after a single episode of myocardial ischemia remains controversial. Therefore, eight conscious dogs were instrumented with ultrasonic dimension transducers and left ventricular micromanometers. Each animal underwent (in random sequence, 72 h apart) a single 15-min left anterior descending coronary arterial (LAD) occlusion and two 15-min LAD occlusions separated by 1 h of reperfusion. The preload recruitable work area (PRWA; the area beneath the regional stroke work vs. end-diastolic length relationship) quantified regional myocardial performance. Repetitive ischemia significantly delayed recovery of PRWA over the first 24 h (P < 0.05). Although postischemic myocardial creep resolved rapidly after single occlusion, double occlusion prevented recovery of creep during the first 4 h of reperfusion. The recovery time course of PRWA paralleled the resolution of myocardial creep, suggesting that creep contributed significantly to delayed functional recovery and that myocardial "stunning" after repetitive ischemia may result in part from interaction between postischemic diastolic properties and systolic dysfunction. PMID- 8476091 TI - Endothelium-derived relaxing factor inhibits norepinephrine contraction of fetal guinea pig arteries. AB - As in the adult circulation, the endothelium may play an important role in determining fetal vascular tone. The purpose of this study was to determine the influence of the endothelium on norepinephrine- and phenylephrine-induced contraction of pulmonary and carotid arteries from near-term fetal guinea pigs. Isometric contractions of isolated rings to the cumulative addition of norepinephrine (10(-9)-10(-5) M) were measured before and after 1) endothelium removal, 2) NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) to inhibit endothelium derived relaxing factor (EDRF), 3) methylene blue (10(-5) M) to inhibit guanylate cyclase, 4) oxyhemoglobin (3 x 10(-6) M) to bind EDRF, and 5) indomethacin (10( 5) M) to inhibit cyclooxygenase. All treatment effects were measured in endothelium-intact segments. The maximal norepinephrine contraction of fetal pulmonary (40 +/- 8% KCl, n = 7) and carotid (13 +/- 7% KCl, n = 7) arteries was much less (P < 0.05) than the maximal contraction to 120 mM KCl. Treatments that inhibit the action of EDRF increased contraction of both fetal pulmonary and carotid arteries. L-NMMA also increased contraction to phenylephrine. Indomethacin had no effect on the contractile responses to norepinephrine of either artery. Thus EDRF inhibits alpha-adrenoceptor-stimulated contraction of fetal pulmonary and carotid arteries and may attenuate the constrictor responsiveness of the fetal circulation in vivo. PMID- 8476092 TI - Single delayed rectifier potassium channels from rabbit coronary artery myocytes. AB - Cell-attached patches from rabbit coronary artery single smooth muscle cells contained two distinct potassium channel types, namely a large conductance calcium-activated potassium channel and a smaller voltage-activated potassium channel representing the delayed rectifier (IK). When a physiological potassium ion gradient was used, the average slope conductance of single IK channels was 7.26 pS. The time course of activation measured from ensemble averages was well fit by a single exponential raised to the power of 2 and was voltage dependent. Experiments were then performed with potassium (140 mM) on both sides of the membrane to resolve single IK channel currents during deactivation. Ensemble averages of this activity were well described by a two-component exponential, and the time constants were voltage dependent. Mean open times were significantly shorter during deactivation than during activation. Closed time distributions typically had two components. These kinetic characteristics were used in testing various state models for voltage-dependent potassium channels. PMID- 8476093 TI - Effects of epoxyeicosatrienoic acids on isolated hearts and ventricular myocytes. AB - Effects of cytochrome P-450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETS; 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET), were examined in isolated guinea pig hearts and ventricular myocytes. Addition of 1-16 ng/ml EETs to normal isolated hearts produced no effects on contractility or coronary pressure. In hearts subjected to 60 min of low-flow ischemia, impairment of contractility and declines in heart rate and coronary perfusion pressure were similar in the presence or absence of 1 ng/ml EETs. However, in the presence of either 5,6- or 11,12-EET, recovery was delayed for the first 10 min only. No significant differences were found in any group regarding heart rate, coronary perfusion pressure, or energy metabolite content after 30 min of reperfusion. In myocytes, both 5,6- and 11,12-EET (100 pg/ml, 1.0 ng/ml, and 20 ng/ml) significantly increased cell shortening as well as intracellular calcium concentrations, whereas 8,9- or 14,15-EET was without effect on these parameters. These results describe for the first time the direct effects of various EETs on cardiac cell function as well as their ability to modulate some of the myocardial responses to postischemic reperfusion. The results suggest a potential role for these substances in the response of the heart to pathological insult. PMID- 8476094 TI - TNF-alpha release in endotoxemia contributes to neutrophil-dependent pulmonary edema. AB - We examined whether the generation of tumor necrosis factor (TNF-alpha) after lipopolysaccharide (LPS) challenge contributes to increases in lung vascular permeability and water content. Guinea pig lungs perfused at constant flow with Ringer-albumin solution (0.5 g/100 ml) were challenged for 120 min with LPS (Escherichia coli; final concentration 33 ng/ml; n = 5). Lung effluent samples were assayed for TNF-alpha activity using the modified L-929 fibroblast cytolytic assay. TNF-alpha concentrations increased in a time-dependent manner with a peak value of 100 +/- 20 pg/ml noted 90-120 min after LPS. Human neutrophils [polymorphonuclear leukocytes (PMN; 2 x 10(7)] added to the perfusion solution after endotoxin challenge (n = 5) produced a threefold increase in lung tissue myeloperoxidase (MPO) activity over control values. PMN, added after LPS and activated using phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M; n = 6), produced three- to sixfold increases in mean pulmonary arterial pressure (Ppa) and pulmonary capillary pressure (Pcap), wet weight-to-dry weight ratio (W/D), and the pulmonary capillary filtration coefficient (Kf,c) over control values (P < 0.05). Activation of PMN with PMA in non-LPS-challenged lungs produced only threefold increases in Ppa and Pcap and did not change W/D and Kf,c. Infusion of an anti-TNF-alpha antibody before the LPS challenge reduced by approximately 50% the increases in Ppa, Pcap, MPO content, Kf,c, and lung wet weight gain (P < 0.05). Therefore, endotoxin-induced TNF-alpha generation in lungs significantly contributes to pulmonary sequestration of PMN. Activation of the sequestered PMN increases pulmonary vascular permeability and tissue water content. PMID- 8476095 TI - Trauma-hemorrhage and resuscitation in the mouse: effects on cardiac output and organ blood flow. AB - Although mice are widely used for the study of immune consequences of hemorrhage, the changes of cardiac output (CO) and blood flow (BF) in response to trauma and hemorrhage in this species have not been well defined. To study this, nonheparinized C3H/HeN mice (n = 6 per group) underwent laparotomy (i.e., trauma induced), were bled to a mean arterial pressure of 35 mmHg, and maintained for 90 min by withdrawing more blood or returning Ringer lactate. The animals were then resuscitated with four times the volume of maximal bleedout in the form of Ringer lactate over 60 min. Sham-operated mice underwent the same procedure but were neither bled nor resuscitated. At the end of hemorrhage, 60 min postresuscitation, or corresponding time after sham operation, CO and BF were determined by radioactive microspheres. Results indicate that CO and BF decreased significantly at the end of hemorrhage. Resuscitation, however, restored CO and BF in various organs except the brain and skeletal muscle. Despite this, 9 of 16 mice died within 6 days postresuscitation, whereas none of sham mice died (n = 16 per group in this additional study). Therefore, we have developed a nonheparinized model of trauma-hemorrhage and resuscitation in mice that is associated with late mortality. Furthermore, the microsphere technique provides a reliable method for assessing CO and BF in mice. Thus it may be possible to study the correlation between cardiovascular and immunologic alterations under such conditions. PMID- 8476096 TI - Spontaneous contractions of isolated bat wing venules are inhibited by luminal flow. AB - The hypothesis that spontaneous contractions of bat wing venules could be modulated by luminal flow was tested. Single venules (114 +/- 5 microns diam) from the wings of anesthetized pallid bats were dissected, cannulated, and pressurized in vitro. A dual reservoir system was used to independently control luminal pressure and flow. In the absence of flow, and with pressure set to 10 cmH2O, all venules contracted spontaneously at rates between 20 and 40 cycles/min. Pressure elevation over the range of 3-10 cmH2O caused a rapid increase in contraction frequency and decrease in amplitude; pressure reduction caused a rapid decrease in contraction frequency and increase in amplitude. In contrast, initiation of flow resulted in a delayed and gradual reduction of contraction amplitude and/or frequency (sometimes to zero). The net effect of flow was to increase mean diameter and decrease the product of frequency x cross sectional area. Flow-induced inhibition of venular contraction was eliminated by endothelial denudation but persisted in the presence of NG-monomethyl-L-arginine (10(-4) M) or indomethacin (10(-5) M) in concentrations that blocked the effects of exogenously applied ATP or arachidonic acid, respectively. The flow-induced venular response also persisted in the presence of superoxide dismutase (55 U/ml). Denuded venules responded to flow when placed downstream (i.e., perfused in series) from venules with intact endothelium. These results indicate that luminal flow can modulate the contractile function of bat wing venules via release of a transferable substance from the endothelium. The exact nature of the substance is not yet known but it does not appear to be classical endothelium derived relaxing factor, a prostaglandin, or an oxygen radical. PMID- 8476097 TI - L-arginine analogues blunt prostaglandin-related dilation of arterioles. AB - The effects of arginine analogues, inhibitors of endothelium-derived nitric oxide synthesis, on dilation of arterioles in response to various vasoactive substances were studied. At 65 mmHg intravascular pressure, isolated arterioles of rat cremaster muscle developed tone spontaneously and achieved control diameters similar to those observed in vivo (84.1 +/- 2.0 microns vs. passive diameter: 161.3 +/- 3.4 microns). Acetylcholine (ACh, 5 x 10(-8) M), sodium nitroprusside (SNP, 5 x 10(-8) M), arachidonic acid (AA, 10(-7) M), prostaglandin E2 (PGE2, 10( 9) M), and adenosine (ADO, 10(-6) M) were added to the Krebs bicarbonate buffer solution, suffusing the vessels. The peak vasodilator effects of all agents were studied before and after the administration of various doses of N omega-nitro-L arginine (L-NNA; 10(-5), 10(-4), and 10(-3) M), which significantly reduced, in a dose-dependent manner, the basal diameter of arterioles by 3.6, 15.2, and 18.9%, respectively. The lowest concentration of L-NNA significantly inhibited arteriolar dilations to ACh by approximately 26%. Higher concentrations of L-NNA and N omega-monomethyl-L-arginine (L-NMMA; 10(-4) M) caused a further significant reduction in the dilation to ACh (to approximately 47%) and also significantly reduced dilator responses to AA and PGE2. In the presence of the highest concentration of L-NNA (10(-3) M), dilation to SNP and ADO were also significantly reduced. Removal of endothelium abolished dilation to ACh and AA but did not alter that to SNP, PGE2, or ADO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476098 TI - Acute resetting of the carotid sinus baroreflex by aortic depressor nerve stimulation. AB - The effect of prolonged aortic depressor nerve (ADN) stimulation on carotid sinus baroreflex regulation of arterial pressure (AP) and renal sympathetic nerve activity (RSNA) was examined in anesthetized rabbits. Ramp increases in carotid sinus pressure (CSP) were repeated before and after 5 min of bilateral ADN stimulation. One minute after ADN stimulation the curve relating AP to CSP had shifted up and to the right, characterized by significant increases (P < 0.05) in the maximum (91 +/- 2 to 101 +/- 3 mmHg; mean +/- SE), midpoint (118 +/- 7 to 125 +/- 8 mmHg CSP), and minimum (45 +/- 3 to 53 +/- 4 mmHg) of the AP reflex curve. There was a parallel shift downward of the curve relating RSNA to CSP, characterized by significant decreases in the maximum [100 +/- 0 to 66 +/- 8% of maximum control RSNA value (%max)], the range (90 +/- 2 to 59 +/- 8%max), and the gain (-1.0 +/- 0.2 to -0.5 +/- 0.1%max/mmHg) of the RSNA reflex curve. Values returned to control within 10 min of cessation of ADN stimulation. These results suggest that central neurons processing baroreflex information from one set of mechanoreceptors can be reset by convergent signals arising from another baroreceptor site. PMID- 8476099 TI - Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics. AB - We investigated the cerebral blood flow (CBF) response to somatosensory stimulation. Stimulation of neuronal activity was performed by deflection (2-3/s) of the mystacial vibrissae in rats over a period of 60 s, and regional cortical CBF was measured continuously in the contralateral somatosensory cortex with laser-Doppler flowmetry. CBF within the somatosensory cortex was studied through the parietal bone thinned to translucency (n = 7) or through a closed cranial window with the dura mater removed (n = 7). In addition, the differential effect of anesthetics (halothane-N2O, n = 5; thiobutabarbiturate, n = 5; and alpha chloralose, n = 7) on the CBF response to stimulation was investigated. After a rapid increase after stimulation onset (maximum reached within 2-3 s), CBF remained above baseline with a slight tendency to decrease despite continued stimulation. On termination of stimulation, CBF fell to near prestimulation values within 2-3 s. The following mean CBF responses above baseline during the 60-s stimulation period were obtained: halothane-N2O anesthesia, 25.4 +/- 5.9%; thiobutabarbiturate anesthesia, 10.6 +/- 2.4%; and alpha-chloralose anesthesia, 16.9 +/- 2.3 (through the translucent bone) and 16.2 +/- 2.9% (closed cranial window, dura removed). We conclude that coupling of CBF to neuronal function has a very high temporal resolution (< 3 s) and that whisker deflection in rats provides a physiological stimulus to study coupling with laser-Doppler flowmetry. PMID- 8476100 TI - Continuous assessment of hemodynamic control by complex demodulation of cardiovascular variability. AB - Usefulness of complex demodulation (CDM) in assessing the frequency components of cardiovascular variability was assessed and, subsequently, this technique was utilized to determine the time-dependent responses of the low-frequency (LF) and high-frequency (HF) amplitudes of heart rate and blood pressure variabilities during postural tilt. CDM provides the time-dependent changes in amplitude of a particular frequency component on a continuous basis. Analysis of simulated data showed that CDM has sufficient frequency resolution to separately measure LF and HF amplitudes with a time resolution < 15 s and that CDM is robust to alterations in the frequency of the components. Analysis of actual data during postural tilt test in 23 young healthy subjects demonstrated that the HF amplitude of heart rate, an index of cardiac parasympathetic tone, rapidly decayed with head-up tilt (P < 0.01) and increased quickly showing an overshoot with tilt back to the supine position (P < 0.01). The LF amplitude of blood pressure, an index of vasomotor sympathetic activity, showed marked rhythmic fluctuation at an interval of 48-100 s during head-up tilt (P < 0.01), synchronizing with similar fluctuation in the LF amplitude of heart rate (P < 0.01). These results suggest that CDM can be used to provide a continuous assessment of cardiovascular variability components and that the dynamic responses of autonomic circulatory control to upright posture result in a phasic modulation of LF amplitude. PMID- 8476101 TI - Near-wall excess of platelets induced by lateral migration of erythrocytes in flowing blood. AB - In this study we present experimental data on the inhomogeneous distribution of platelets in polyethylene tubes (200 microns diam) based on the inverse Fahraeus effect for platelets. It is shown that platelets are expelled toward the red blood cell-depleted marginal layer near the tube wall by mutual interaction with erythrocytes. By means of a straightforward model, the near-wall concentration of platelets could be estimated from measurements on the average tubular platelet concentration. The marginal layer originates from the hydrodynamic interaction of the deformable erythrocytes with the tube wall. If the tube diameter is large compared with the size of the erythrocytes, the lateral migration effects can effectively be scaled on the absolute distance between the erythrocytes and the tube wall. This results in the main conclusion that the near-wall concentration of platelets is significantly enhanced up to about seven times the average concentration, practically irrespective of the tube diameter in the range of 100 500 microns. Where comparable, the results of this study are in accordance with experimental data of other authors. PMID- 8476102 TI - Modulation of cerebral arterial tone by endothelium-derived relaxing factor. AB - This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT. PMID- 8476103 TI - Comparison of conduit vessel and resistance vessel reactivity: influence of intimal permeability. AB - Arterioles of hamster cheek pouches are less reactive to luminal application of small hydrophilic agents than to adventitial application. To explore possible longitudinal variations in response sidedness, we compared reactivity of isolated vessels from carotid arteries to first-order arterioles. Concentration-response curves for luminally or adventitially applied phenylephrine (PE) were constructed. Arterioles were 274-fold less responsive when PE was in luminal vs. adventitial responsiveness decreased as vessel diameters increased, from 24-fold in inferior saccular arteries to 18-fold in external maxillary arteries and, finally, to 3-fold in common carotid arteries. Differences in response to luminal or adventitial application of PE could be eliminated in arterioles by perfusion with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), which disrupts membrane integrity. Treatment with CHAPS also increased the transmural movement of sodium fluorescein across arteriolar vessel walls. We conclude that a diffusion barrier exists in arterial walls, that there is a longitudinal variation in this barrier as expressed by the differences in movement of small hydrophilic molecules from lumen to smooth muscle cell layers, and that the site of the barrier is likely to be at the endothelial cell membrane. PMID- 8476104 TI - Distribution, propagation, and coordination of contractile activity in lymphatics. AB - The propagation and coordination of lymphatic contractions were studied in the mesentery of the rat small intestine using in situ microscopic observation. Indexes of lymphatic diameter were simultaneously measured at two adjacent lymphangions in spontaneously contracting lymphatics (n = 51). Diameter index, contraction frequency, and the percentage of the intersegmental contractions that were propagated and coordinated (PP) were determined at both sites. The conduction velocity of the contractile activity and the percentage of the coordinated contractions that were propagated both antegrade to the direction of lymph flow and retrograde to the flow stream were determined. The results indicate that 1) 80-90% of the lymphatic contractions in the vessels we evaluated were propagated, 2) the wave of contractile activity propagated both centrally and peripherally, and 3) the conduction velocity of the contractile activity was approximately 4-8 mm/s. We tested the hypothesis that gap junctional communication is responsible for the coordination of the contractile event. To accomplish this, we used the gap junction blockers n-heptanol and oleic acid. PP was 90 +/- 4% under normal conditions and fell to a minimum value of 55 +/- 7% during the gap junction blockade. These results indicate that gap junctional communication played an important role in the propagation and coordination of contractions that occurred in spontaneously active lymphatics. PMID- 8476105 TI - Constrained optimization of ventricular efficiency in normal and failing hearts. AB - Optimal ventriculoarterial coupling, in terms of maximal energetic efficiency, was recently analyzed by analytic and experimental studies. Whereas for normal hearts the analytic predictions agreed well with measured data, failing hearts were found to operate remote from the predicted optimal conditions. An analysis of optimal coupling is developed in the present study, based on constrained optimization. The constraints are based on the concept that the system must comply with physiological requirements (restrictions) under all conditions. Optimization using the mean pressure as a constraint yielded results similar to the unconstrained case in the normal heart but different with the failing heart: in the failing heart the optimal arterial elastance was found to be larger than the ventricular elastance, whereas the opposite was predicted by the unconstrained optimization. If an additional constraint on the end-systolic pressure is used, a unique solution of the coupling state is obtained. The predicted coupling ratio was found to match published data from normal subjects and heart failure patients, where in the latter group it was found to be remote from the optimal efficiency state. An increase in ventricular contractility and reduction in afterload were shown to shift the nonoptimal coupling state toward the optimal one. This prediction complies with the use of inotropic agents and vasodilators as the mainstay of heart failure treatment. This study may provide a convenient framework of analysis for the assessment of the ventriculoarterial coupling and for the evaluation of the cardiovascular effects of specific drug treatments. PMID- 8476106 TI - Progressive feline pressure-overload: noninvasive assessment correlates with abnormalities in single cells. AB - Serial echocardiography and Doppler were used to monitor the progression of pressure-overload produced by banding the ascending aortas of young cats. The peak Doppler gradient across the band increased (as the animals grew in size) from 42 +/- 4.2 mmHg at 1 wk to 78 +/- 4.5 mmHg at 2-3 mos. Echocardiographic measurements of septal wall thickness increased significantly at 1 wk. Global ventricular function was unaltered in banded cats versus shams at each time point. However, in the subgroup of animals with an aortic-constricted area of < 0.025 cm2 at 1 wk, fractional shortening decreased by 40% at 2-3 mos. Contractile abnormalities were present in isolated myocytes from hypertrophied hearts. Mechanical function was more profoundly depressed in cells from hearts with echocardiographic evidence of ventricular decompensation. Echocardiographic and Doppler studies assessed cardiac size and function and identified indexes predictive of global and cellular myocardial dysfunction. The use of noninvasive techniques as a predictor of failure makes the feline model of progressive left ventricular pressure-overload useful for studies of cellular and molecular factors regulating not only the development of cardiac hypertrophy but also the transition from compensated hypertrophy to myocardial failure. PMID- 8476107 TI - Loss of cardiac myofibrils: mechanism of contractile deficits induced by taurine deficiency. AB - It is well established that taurine deficiency is associated with myocardial contractile dysfunction; however, the mechanism is unknown. As a follow-up to finding reduced force generation in taurine-depleted rat cardiac trabeculae, using either calcium or strontium activation, this study examined alterations in ventricular fine structure and contractile proteins in animals made taurine deficient by in vivo treatment with a taurine transport antagonist, guanidinoethane sulfonate. Observations of ventricular ultrastructure showed disordered contractile filaments and clear losses of myofibrillar bundles in association with taurine deficiency. Biochemical analyses of ventricular contractile proteins using polyacrylamide gel electrophoresis confirmed losses of the major sarcomeric proteins, myosin and actin. These findings provide a possible mechanism for the contractile deficits and cardiomyopathy described in taurine-deficient animals. PMID- 8476108 TI - Chemically induced hypotension increases PGE2 release and depresses macrophage antigen presentation. AB - Hemorrhagic shock causes severe depression of macrophage functions and is associated with increased susceptibility to sepsis. Because hemorrhagic shock and resuscitation encompasses several pathophysiological conditions, such as hypotension, low-flow conditions, hypoxia, and reperfusion injury, it remains unknown whether severe hypotension in the absence of blood loss has any adverse effects on macrophage functions. To study this, systemic arterial hypotension was induced in C3H/HeN mice for 15 min by intravenous infusion of sodium nitroprusside or ATP-MgCl2. Peritoneal macrophages (PM) was harvested 20 h later with lavage. Antigen presentation was measured by coculturing PM with the D10.G4.1 Th cell clone. Tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, and prostaglandin (PG) E2 levels in supernatants of PM stimulated with lipopolysaccharide were measured with bioassays or radioimmunoassay. Systemic arterial hypotension resulted in a significant decrease of PM capacity to present antigen. Although the release of TNF, IL-6, and IL-1 by PM was unaltered after hypotension, PGE2 release by PM was significantly elevated compared with the control group. These data indicate that chemically induced systemic arterial hypotension without blood loss leads to a depression of antigen presentation, which may be caused by elevated release of the immunosuppressive eicosanoid PGE2. PMID- 8476109 TI - Neurogenic control of renal function in response to graded nonhypotensive hemorrhage in conscious dogs. AB - The reflex control of plasma renin activity (PRA) and urinary sodium excretion (UNaV) was evaluated in 13 dogs instrumented for chronic study and maintained on a normal sodium intake (40 meq/day). Graded blood volume depletion of 14 (BVD1) and 21% (BVD2) of the estimated total blood volume was used to activate renal sympathetic nerve activity (RSNA), and experiments were conducted before and after bilateral renal denervation (DNX). In dogs with innervated kidneys, nonhypotensive BVD1 increased RSNA 40.9 +/- 10.9% (P < 0.05) above control. Blood volume depletion increased PRA from 1.95 +/- 0.52 to 3.5 +/- 0.57 ng.ml-1 x h-1 and decreased UNaV from 58.2 +/- 10.1 to 35.5 +/- 4.3 mu eq/min without changing renal blood flow or glomerular filtration rate. BVD2 failed to further activate RSNA (52.0 +/- 16.7%) but did increase PRA to 4.85 +/- 0.83 ng.ml-1 x h-1 and decreased UNaV to 17.9 +/- 2.7 mu eq/min. Renal DNX (n = 13) abolished both the PRA and antinatriuretic responses to BVD1 and BVD2. Thus volume-invoked reflex activation of RSNA, but not altered renal hemodynamics, mediates, activation of PRA and antinatriuresis. This neurogenic control of renal function may be critical to the rapid regulation of extracellular fluid volume, via alterations in urinary excretion. PMID- 8476110 TI - Glomerular hemodynamics in aortocaval fistula rats: role of renin-angiotensin system. AB - To investigate intrarenal hemodynamics of aortocaval, arteriovenous (AV)-fistula rats and the effect of angiotensin-converting-enzyme (ACE) inhibition, micropuncture studies were obtained before and after administration of quinapril (100 micrograms.kg-1 x min-1), an ACE inhibitor. AV fistula produced by needle multipuncture was characterized by elevated left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and increased left and right ventricular weights. Effective renal plasma flow was lower in AV-fistula rats, and single-nephron glomerular filtration rate (SNGFR) and plasma flow (SNPF) were reduced. Single-nephron filtration faction (SNFF), stop-flow pressure, and glomerular pressure (PG) were increased. The lower SNGFR and SNPF and higher PG and SNFF were associated with higher afferent and efferent arteriolar resistances (RA and RE) and lower ultrafiltration coefficient (Kf). LVEDP correlated positively with with RA, RE, and SNFF (all P < 0.01) and negatively with SNGFR (P < 0.05) and SNPF (P < 0.01). After quinapril these variables returned toward normal. Thus this method for producing AV fistula was useful in creating mild and moderately severe cardiac failure (CHF). Intrarenal hemodynamics of AV were characterized by increased PG and SNFF and lower SNGFR and SNPF associated with increased RA and RE and lower Kf and SNPF correlated and with severity of CHF. Restoration of intrarenal hemodynamics to or toward normal with quinapril supports an important pathophysiological role of renin-angiotensin system in this CHF. PMID- 8476111 TI - Mechanisms of acute hemoconcentration in bullfrogs in response to hypoxemia. AB - Three general mechanisms have been proposed to explain rapid increases in red blood cell concentration in vertebrates in response to hypoxia: spleen emptying, red blood cell swelling, and decreases in plasma volume. We have experimentally tested these potential mechanisms for the hemoconcentration of red blood cells associated with hypoxemia in cold (10 degrees C), submerged bullfrogs. The mean increase of hematocrit was approximately 1.4-fold (the increase was highly variable between individual frogs) when arterial oxygen saturation was reduced from 80% to 8% by lowering ambient O2 partial pressure (PO2). The largest response was seen when arterial oxygen saturation was below 33% (a saturation that is not unusual in submerged amphibians). There was no difference between hematocrit increases during hypoxemia in spleen-ligated compared with sham operated frogs submerged in hyperoxic, normoxic, and hypoxic water, suggesting that spleen emptying is not the primary mechanism. Increased hematocrit was not due to red blood cell swelling: mean corpuscular hemoglobin concentration increased slightly as hematocrit increased, indicating that red blood cells shrank slightly rather than swelling. Plasma volume, measured in a separate group of animals by dilution of 51Cr-labeled autologous red blood cells, decreased almost 50% during hypoxemia, closely correlated with a mean increase of 1.76-fold of hematocrit. We thus conclude that the hematocrit increase seen during hypoxemia in bullfrogs is caused by a loss of plasma volume. This has important implications for cardiovascular function, since blood viscosity, oxygen carrying capacity, and cardiac output are all affected by changes in plasma volume. PMID- 8476112 TI - Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney. AB - To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476113 TI - Regional adrenergic regulation of ion transport across the isolated porcine gallbladder. AB - The regional transport properties of the porcine gallbladder epithelium were studied using Ussing chambers in which tissues were bathed in porcine Ringer solution. Under basal conditions, tissues from the neck absorbed Na and Cl. Fundic tissues also absorbed Na, but net Cl transport was not different from zero. Serosal norepinephrine (NE; 0.1 microM) stimulated Na and Cl absorption in the neck but only Cl absorption in the fundus. The effects of NE on Na and Cl transport were blocked by pretreatment with yohimbine, suggesting that alpha 2 adrenoceptors mediate the transport-related actions of this neurotransmitter. Serosal isoproterenol (0.1 microM) produced a tetrodotoxin-insensitive, propranolol-sensitive increase in the short-circuit current (Isc) in fundic tissues but not in tissues from the neck. The beta 2-adrenergic agonist salbutamol produced a response similar to that of isoproterenol. However, the beta 1-adrenergic agonist dobutamine had no effect. Isoproterenol was 5.8-fold more potent than salbutamol in increasing the Isc. A possible explanation for the regional effects of beta-agonists is that beta-adrenoceptors are localized to epithelial cells in the fundic region. These results and results obtained previously suggest regional differences in basal Na and Cl transport across the porcine gallbladder epithelium and that both alpha 2- and beta 2-adrenoceptors act to regulate ion transport in this tissue. PMID- 8476114 TI - Restricted food access and light-dark: impact of conflicting zeitgebers on circadian rhythms of the rabbit. AB - Free-running circadian rhythms of rabbits were exposed to a 11:55-11:55-h light dark (LD) schedule. After complete entrainment (63 +/- 22 days), the predominantly nocturnally active rabbits were exposed to an additional zeitgeber, restricted food access (RF), which was imposed during the light period. In five animals RF had the same period (T) as the LD cycle (23:50 h), and in five other animals TRF was 24:10 h. At a period of 23:50 h for both zeitgebers, the rhythms of four animals were stably entrained to RF, while in one animal a component of the rhythm broke away from RF and entrained to the LD zeitgeber. In animals exposed to zeitgebers of different periods most of the activity rhythm also entrained to RF, but 20 +/- 7% of the activity entrained to the LD zeitgeber. The light-entrained activity component merged with the RF component when the zeitgebers crossed, and decomposition occurred when the phase difference exceeded 4-6 h. The results indicate that two circadian oscillator systems exist in the rabbit, one entrained by light-dark cycles and the other by feeding-fasting cycles. Both exert common control over a number of overt behavioral rhythms. PMID- 8476115 TI - Effects of estrogen on gluconeogenesis and related parameters in male rainbow trout. AB - To investigate the effects of estrogen, the hormone responsible for vitellogenesis, on gluconeogenesis, male rainbow trout were implanted with 17 beta-estradiol or given a sham procedure. Plasma glucose concentration in estrogenized fish was 50% of the control fish (6.4 mM). Glucose synthesis from physiological concentrations of alanine was 0.08 mumol.g cells-1 x h-1 compared with 0.20 mumol.g cells-1 x h-1 in control fish; synthesis from physiological concentrations of lactate was reduced by over 50% (0.88 vs. 0.36 mumol.g cells-1 x h-1) in implanted fish. Gluconeogenesis from 5 mM lactate was also significantly depressed in implanted fish. Oxidation of alanine, serine, and lactate was not significantly affected by estrogen implantation. The maximum clearance velocity of a key enzyme negatively regulating gluconeogenesis, pyruvate kinase, was 3.03 mumol.g cells-1 x h-1 in estrogen (E2) implanted fish compared with 7.83 mumol.g cells-1 x h-1 in control fish. No significant differences in plasma insulin or glucagon were found in the two groups. We conclude that estrogen depresses gluconeogenesis and that this reduction contributes to the lower plasma glucose concentration seen in vitellogenic trout. PMID- 8476116 TI - Organ specificity of the dopamine1 receptor/adenylyl cyclase coupling defect in spontaneously hypertensive rats. AB - The coupling between the dopamine1 (DA1) receptor and the G protein/adenylyl cyclase (AC) enzyme complex is defective in the proximal convoluted tubule (PCT) of 20-wk-old spontaneously hypertensive rats (SHRs). Because this coupling defect could have been due to desensitization secondary to elevated renal dopamine levels in the adult animal, we studied the interaction between DA1 receptors and AC in PCT of rats as early as 3 wk of age, a time when renal dopamine levels are similar in SHRs and their normotensive controls (Wistar-Kyoto rats, WKYs). Maximum receptor density did not change with age and was similar in WKYs and SHRs in all the age groups studied (3, 8, and 20 wk). Basal-, forskolin-, and guanyl nucleotide-stimulated AC activities were also similar in WKYs and SHRs and did not change with age. However, the DA1 agonist-stimulated AC activity was greater in WKYs than in SHRs and increased with age in WKYs but not in SHRs. Moreover, the ability of a nonhydrolyzable analogue of GTP, Gpp(NH)p, to enhance DA1 agonist (SND-919-C12, 1 microM)-stimulated AC activity increased with age in WKY but not in SHRs. To determine if the defect noted in the PCT of SHRs is due to a defective D1A receptor gene, parallel studies were performed in the striatum, since this receptor is expressed predominantly in the latter tissue. In contrast to the results in PCT, radioligand binding and AC studies in striatum revealed no differences between WKYs and SHRs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476117 TI - The effect of a low essential fatty acid diet on hibernation in marmots. AB - We investigated the effect of an essential fatty acid (EFA)-deficient diet on hibernation patterns in yellow-bellied marmots (Marmota flaviventris). Fatty acid (FA) analysis of white adipose tissue (WAT) from animals maintained for 2 mo on the EFA-deficient diet suggested that little or no EFAs were present in the gonadal or omental fat depots. Hibernation about lengths of the EFA-deficient animals were significantly shorter (P < 0.01) than control animals. Stated another way, these animals aroused twice as frequently compared with control animals and used more energy to survive winter. Analysis of WAT composition and blood samples revealed that animals were highly lipolytic during winter. Furthermore, the release of FAs was not random: linoleate (cis-9,cis-12 octadecadienoic acid; 18:2, a diene EFA) was significantly (P < 0.05) under represented in venous outflow from the gonadal WAT pad based on the percentage of this species in WAT. The concentration of saturated FAs was higher than that predicted from the WAT-FA composition. We conclude that linoleate is preferentially retained within WAT and that concentrations of this EFA may influence hibernation behavior. Thus EFAs may have a thermoregulatory role in hibernation in addition to their role as essential precursors for physiologically important lipids after hibernation is over. PMID- 8476118 TI - Changes in extracellular [K+] and [Ca2+] induced by anoxia in neonatal rabbit medulla. AB - Ion-selective microelectrodes were used to record levels of extracellular K+ and Ca2+ concentrations ([K+]o and [Ca2+]o, respectively) and the changes evoked by anoxia in the medulla of anesthetized ventilated newborn rabbits, 1-14 days of age. Resting levels of [K+]o showed significant decline with increasing age. The mean initial level of [K+]o was 6.5 +/- 0.3 mM for the 1st neonatal wk and 5.1 +/ 0.4 mM for the 2nd wk. Brief periods of N2 inhalation (1-3 min) induced reversible increases in [K+]o that were smaller with progression of maturity. The duration of the initial increase (phase I) in [K+]o was twofold greater during the 1st wk than the 2nd wk. At the maximal steady-state level of change (phase III), [K+]o increased by 1.8 +/- 0.2 mM during wk 1 and by 0.9 +/- 0.1 mM during wk 2. Large transient bursts of increase were frequently observed during both early and recovery phases of the sustained [K+]o accumulation. Resting levels of [Ca2+]o also showed age dependence. The mean values during early neonatal days 1 3, compared with days 7-10, were 3.7 +/- 0.3 and 2.4 +/- 0.6 mM, respectively. Anoxia evoked multiphasic decreases in [Ca2+]o that were largest in the youngest pups. Early transient falls of 0.5 +/- 0.1 mM occurred at times similar to those for the earliest increases of [K+]o and negative focal potentials; larger decreases (0.9 +/- 0.2 mM) were recorded after reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476119 TI - Functional adaptation of different rat skeletal muscles to weightlessness. AB - The adaptation to weightlessness of two postural muscles, the slow soleus (SOL) and the fast gastrocnemius lateralis (GL), and a fast muscle used in movements, the extensor digitorum longus (EDL), was studied on five adult Wistar rats. The animals exposed to 14-day spaceflight aboard COSMOS 2044, designated as flight (F), were compared with synchronous (S) animals. The experiments were performed on single skinned fibers whose functional properties were studied. After weightlessness, the SOL exhibited two populations of fibers according to their Sr2+ affinities: 40% remained slow (Fs) and 60% acquired fast-type properties (Ff). Both S and F GL and EDL showed a single distributed population of fast fibers. SOL fibers atrophied insofar as they showed a significant reduction in fiber diameter and absolute maximal tension Po (mg) but not in Po expressed in kg/cm2. GL fibers showed no change in fiber diameter but a decrease in Po in mg and kg/cm2. EDL fibers were not atrophied by weightlessness. The tension/Ca concentration relationships of the Ff SOL and F GL fibers were shifted to the right, indicating a decrease in their Ca2+ affinity. An increase in the contraction kinetics was described for the SOL fibers after weightlessness, whereas no significant modification was found for the GL and EDL. Collectively, the data suggested that the adaptive changes subsequent to weightlessness were more dependent on the muscle function than on the fiber type, since both postural SOL and GL were modified. PMID- 8476120 TI - Immunochemical characterization and localization of endothelin ETB receptor. AB - A highly specific antiserum was raised against purified bovine endothelin ETB receptor and used to determine the tissue distribution of the receptor subtype ETB and to localize the receptor immunohistochemically in the kidney, adrenal gland, lung, cerebellum, and pituitary gland whose functions are known to be under strong influence of endothelin. The antiserum raised in a rabbit specifically recognized the receptor band on Western blot analysis of membrane proteins. Furthermore, it immunoprecipitated only ETB, establishing its ETB specificity. By determination of the percentage of the total number of the endothelin receptors that is immunoprecipitable with the antiserum, the amounts of the ETB relative to those of the ET receptors were found to vary from tissue to tissue: lung (70%), cerebellum (55%), pituitary gland (50%), kidney (25%), adrenal gland (10%), and testis (< 2%). This means that, in the lung, ET is the major form, whereas in the testis, ETA is predominant, comprising >95% of the receptors. Immunohistochemical examination of tissue sections revealed endothelium localization of the ETB endothelin receptor. PMID- 8476121 TI - Cardiovascular change and hypothalamic norepinephrine release in response to environmental stress. AB - The major objective of this study was to compare the magnitude and duration of cardiovascular (CV) responses to acute environmental stresses with the associated patterns of noradrenergic activity in the paraventricular nucleus (PVN) and posterior nucleus (PH) of the hypothalamus. Simultaneous microdialysis samples of extracellular norepinephrine (NE) were collected at 5-min intervals from PVN and PH and the CV responses were recorded before, during, and for 15 min after acute shaker (cage oscillation) stress or inhalation of ether vapor in freely moving rats. Five minutes of shaker stress, 60 and 150 cycles/min, elicited pressor responses coupled with increases in dialysate NE from both PVN and PH in a frequency-dependent manner. Tachycardia occurred at 150 but not 60 cycles/min. Ten minutes after 60 cycles/min and 15 min after 150 cycles/min, NE efflux in PH was still increased, whereas in PVN it returned to control as had arterial pressure and heart rate. Ether vapor elicited a transient CV response but a continuing efflux of NE in PH and PVN. Urethan anesthesia raised baseline values of dialysate NE in PH and PVN but significantly attenuated cardiovascular and dialysate NE responses to shaker stress. We conclude that acute environmental stress simultaneously elicits CV responses and the efflux of NE from PVN and PH but, during or after stress, CV values may return to control levels while NE efflux remains elevated in PVN and/or PH. PMID- 8476122 TI - Water uptake in stimulated cat skeletal muscle. AB - Isolated vasodilated cat hindlimb skeletal muscles were perfused at constant flow and stimulated at 4 Hz for 2-4 min in three studies. Water uptake rates were measured gravimetrically or calculated from venous protein concentration changes. Venous plasma sodium, potassium, chloride, and osmolality were also measured. Maximum water uptake rates averaged 1.8 +/- 0.2 (SE) ml.min-1 x 100 g-1, reaching twice that in some experiments. Water uptake continued after stimulation had ceased. Constant-flow perfusion maintained a constant capillary pressure that was corroborated by measurements of arterial and venous perfusate pressures. Water uptake rate was not influenced by hematocrit but was highly correlated with plasma flow rate. The evidence strongly suggests that small-molecule osmotic pressure was the primary pressure causing the transcapillary water flux. Venous plasma sodium and chloride concentrations increased almost as much as protein (108 and 87% of the protein increase, respectively), as would be expected when water fluxes are driven by small-molecule osmotic pressure. Peak potassium efflux averaged 36 +/- 3 mu eq.min-1 x 100 g-1, but potassium did not contribute significantly to the osmotic gradient. PMID- 8476123 TI - Mismatch between lipid mobilization and oxidation: glycerol kinetics in running African goats. AB - Glycerol kinetics and total fatty acid (FA) oxidation of trained African pygmy goats were measured by continuous infusion of [2-3H]glycerol and indirect calorimetry during treadmill exercise at 40, 60, and 85% maximal O2 consumption (VO2max). Our main goals were 1) to determine whether rates of FA mobilization and utilization are eventually matched as exercise intensity increases, thereby minimizing reesterification to supply more FA to working muscles, and 2) to test the hypothesis that lipolytic rate is proportional to aerobic capacity by comparing low-aerobic goats with published values from highly aerobic dogs and humans. Mean rate of glycerol release in the circulation (Ra glycerol) was 3.83 +/- 0.11 at rest, 7.69 +/- 0.88 at 40% VO2max, reached a maximum of 15.32 +/- 0.95 at 60% VO2max, and returned to 10.53 +/- 0.76 mumol.kg-1 x min-1 at 85% VO2max. Lipolytic rate did not match total FA oxidation, implying that Ra glycerol cannot be used as an index of FA utilization, even during intense exercise. A large fraction of total FA released by lipolysis was reesterified at 60 and 85% VO2max, showing that FA mobilization does not limit whole animal FA oxidation at these intensities. Comparing goat, dog, and human responses reveals that mammalian lipolytic rate is scaled with aerobic capacity. High- and low aerobic species exercising at the same %VO2max mobilize FA in exact proportion with their metabolic rate, suggesting that the relative contribution of FA to total energy provision is independent of VO2max. PMID- 8476124 TI - Membrane properties of organum vasculosum lamina terminalis neurons recorded in vitro. AB - Intracellular recordings of organum vasculosum lamina terminalis (OVLT) neurons were obtained from superfused explants of rat hypothalamus. Most (32 of 34) OVLT neurons displayed a low threshold spike response during depolarizing pulses applied from holding membrane potentials negative to -70 mV. In 17 of 34 cells, electrical stimulation of the supraoptic nucleus area evoked antidromic responses. In 20 of the 34 cells, 8 of which were antidromically driven, identical stimuli also revealed either excitatory (n = 12) or inhibitory (n = 5) or mixed (n = 3) postsynaptic potentials. Axonal projections to the ipsilateral supraoptic nucleus were confirmed afterwards using reconstruction of Lucifer yellow-filled cells. A 10-40 mosmol/kgH2O increase in the osmolality of the superfusion media by addition of NaCl or mannitol prompted a membrane depolarization of 2-10 mV in each of nine OVLT neurons tested. These results indicate that OVLT neurons project to the supraoptic nucleus and possess intrinsic properties capable of influencing their excitability. Because neurons in OVLT depolarize consequent to elevations in media osmolality, the OVLT may provide a means by which hyperosmotic stimuli influence neuroendocrine function. PMID- 8476125 TI - Effect of chronic electrical stimulation on GLUT-4 protein content in fast-twitch muscle. AB - Insulin- and contraction-stimulated skeletal muscle glucose transport is governed largely by the GLUT-4 isoform of the glucose transporter. Recently, it has been demonstrated that denervated muscle has decreased GLUT-4 protein content, suggesting that regulation of GLUT-4 protein is related to neuromuscular activity. However, until now the effects of the opposite situation, enhanced neuromuscular activity, could only be speculated on from exercise training studies. In the present investigation the effect of chronic low-frequency electrical stimulation (10 Hz, 8 h/day) on GLUT-4 protein content and citrate synthase activity was determined in the predominantly fast-twitch plantaris. Chronic electrical stimulation enhanced GLUT-4 protein content and citrate synthase activity in the muscles stimulated for 10-20 days. Electrical stimulation lasting 30-40 days resulted in no further enhancement of GLUT-4 protein content while citrate synthase activity continued to increase. Further prolongation of electrical stimulation (60-90 days) resulted in a plateauing of citrate synthase activity. The results suggest that increased neuromuscular activity can act independently of systemic changes to increase total GLUT-4 protein content. They also suggest that both GLUT-4 protein content and citrate synthase activity are positively related to increased neuromuscular activity but that their rates of increase differ substantially. PMID- 8476126 TI - Object relations issues in the treatment of the preoedipal character. AB - It was through tolerance of Ms. D.'s infantile rage (i.e., rage against reality and its limits) that the analyst was able to open up a dialogue with the patient that could lead to a developmental mourning process. The same was true for the borderline character, Ms. A.! The interpersonal dialogue between analyst and analysand, which had both empathic and interpretive functions, allowed Ms. D. to reactivate her capacities for an intrapsychic dialectic gained during infancy. In her case, as well as in that of Ms. A., the initiation of an internal dialectic allowed for a mourning process to unfold. It is proposed that this internal dialectic is evidence of the existence of the psychic structure necessary to promote both mourning and the mutuality of interpersonal dialogue. The inability to mourn, generally seen in narcissistic and borderline characters, can be seen, therefore, not only as a failure in psychic structure formation, but also as a failure in psychic structure function that is due to intrapsychic defense. PMID- 8476127 TI - Understanding chronic bulimia: a four psychologies approach. PMID- 8476128 TI - A psychoanalytic view of cross-cultural passages. PMID- 8476129 TI - The horror reaction and its importance. PMID- 8476130 TI - Women and men in conversation: normal or neurotic? PMID- 8476131 TI - Creativity and psychosis in scientific research. PMID- 8476132 TI - Freud, three operas, and the affair with Minna Bernays: a reply to O'Brien's interpretation of operatic allusions. PMID- 8476133 TI - [Long-term evaluation of spinal cord electric stimulation in peripheral vascular disease]. AB - We reported an study about the Electric Medullar Stimulation on Peripheral Vascular Pathology, in cases of critical Ischaemia of lower limbs. Short-time and longtime results are exposed. Arteriopathies included into the study were: arteriosclerosis, "mixed arteriopathy and TAO". Examination was made by Doppler Ultrasonography. PMID- 8476134 TI - [Importance of the evaluation of cerebral vasoreactive capacity in the indication for carotid endarterectomy]. AB - In order to evaluate the outcome of endarterectomy, we estimated the cerebral vasoreactive capacity in 3 main patient groups with carotid artery disease: A. occlusion, B. high-grade, and C. low-grade carotid stenosis. The results showed that certain proportion of patients with reduced CVC can be distinguished in the each investigated groups, indicating thus, those patients in whom endarterectomy can benefit. Our study provides evidence that acetazolamide test with TCD measuring may be used to assess the CVC before and after endarterectomy. Carotid endarterectomy improves CVC in patients who had compromised cerebral perfusion reserve before operation. We suggest that the endarterectomy can also benefit in the patients with carotid occlusion and low grade stenosis if CVC is estimated. PMID- 8476135 TI - [Hemodynamic bases for the automatized quantification of the degree of obstruction in peripheral arteries in diabetic patients]. AB - In order to improve the early diagnosis of arterial occlusions, we tried to establish the basis of an automatized system that allowed the study of the hemodynamic features of diabetic patients in the different stadii of their disease. Fifty-four patients with Diabetes Mellitus Type II were included in the study. In all of them, arterial flow curves were carried out at different levels: femoral, popliteal, pedia and tibial posterior arteries of both lower limbs. In the distal arteries of patients with hemodynamic injury, normal values of Maximal Systolic Velocity (Max A), Maximal Diastolic Velocity (Max D), Peurcelot's resistance (PR), pulsatility index (PI) and spectral band (SB), were found. PMID- 8476136 TI - [Renal duplex: clinical usefulness]. AB - It is the purpose of this report to focus attention on the clinical usefulness of Renal Duplex for the diagnosis of patients with vasculo-renal diseases in terms of: 1. Accuracy of Duplex/Angiography in the measurement of the renal stenosis degree. 2. Correlationship between Duplex ans Isotopic Renogram with respect to the study of the parenchyma's perfusion. 3. The effect of the inhibitors of the conversor enzyme (Captopril) on the Doppler signal of the parenchyma, comparing it with the results from the captopril test about the peripheral plasmatic renin activity and the isotopic renogram, in patients with vasculo-renal HTA. Results obtains by Duplex and Angiography were compared in 92 renal arteries from 46 patients. For both technics, three degrees of stenosis were established: 0-59%, 60-99% and occlusion. The Duplex technique identified 49/54 stenosis < 60%, 28/33 stenosis > 60% and 5/5 occlusions (Kappa 0.8). Sensibility and specificity of Duplex for the diagnosis of stenosis > 60% were, respectively, 89.5% and 90.7%; with an exactness of 90.2%. The angiographies showed stenosis > 60% in 23 patients with HTA (diastolic pressures > 100 mmHg). In all of the patients, a measurement of the plasmatic renin activity, an isotopic renogram and a Doppler of the interlobar arteries basal and post-captopril, were performed. The correlationship between Duplex and isotopic renogram with respect to the measurement of the relative renal perfusion was statistically significant (r = 0.91; p < 0.0001). The captopril test for renin and isotopic renogram were positives for 5 patients (4 with unilateral stenosis an 1 with bilateral stenosis). All of them showed severe stenosis (> 80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476137 TI - [Long-term course of arterial traumatisms in children. Analysis of 31 cases]. AB - Thirty children, 17 boys and 13 girls, with 31 arterial traumatisms, were studied. The follow-up period ranged from 4 to 166 months. The purpose of this study was to analyze the long term results. The etiology in 19 cases was accidental (61.3%) and iatrogenic in 12 (38.7%). Upper limbs were affected in 15 cases, lower limbs in 13. The arterial traumatism affected the supra-aortic truncus in 2 patients and the renal artery in one other. Arteriographies were carried out in 7 cases (22.6%). Twenty-three patients (74.2%) underwent surgical procedures. The rest of the patients were managed conservatively. No amputations were needed. Three patients died by no vascular causes. The long-term results were good in terms of permeability and absence of major sequels. We conclude that IAT (Infantile Arterial Traumatisms) are potentially graves; therefore an early diagnosis and a specialized care of patients, without rigid protocols of management, are needed. The uncertain prognosis of IAT obligate to a clinical follow-up. PMID- 8476138 TI - [Complete reconstructions without intermediate anastomoses]. AB - Results from 9 complete reconstructions without intermediate anastomosis (8 patients) are presented. In five cases a by-pass from femoral artery to the contralateral popliteal (infra or supra-rotuliar) arterial prosthesis was performed. In other case a by-pass from the aorta artery to the third popliteal section was placed. Other by-pass was performed from the branches of an axillo bifemoral by-pass to the third popliteal section. The last case was an axillo-bi popliteal by-pass. All the patients presented a severe ischemia (III and IV Fontaine stadii). Eight millimeter PTFE grafts were used. The distal anastomosis should always be performed in vessels with a low distal resistance. PMID- 8476139 TI - Safety and efficacy of total thyroidectomy for differentiated thyroid carcinoma: a 20-year review. AB - Controversy continues to exist regarding the optimal extent of resection for differentiated thyroid carcinoma (DTC). Subtotal thyroidectomy has been advocated by some authors in expectation of lower complication rates, while others advocate total thyroidectomy to achieve better cure rates. To examine this issue, the medical records of 124 patients who underwent total thyroidectomy for DTC were retrospectively reviewed. Total thyroidectomy was the initial procedure in 115 patients, while nine patients had complete thyroidectomy following some type of subtotal resection. Concomitant procedures were performed in 47 patients. Ninety papillary, 20 mixed papillary-follicular variant, one Hurthle cell type, and 13 follicular carcinomas were performed. Tumors were bilateral or multicentric in 40 patients, with metastases present in one-third of patients at the same time of initial operation. Permanent hypoparathyroidism developed in two patients, and permanent ipsilateral recurrent laryngeal nerve palsy occurred in one patient, for an overall significant complication rate of 2.4 per cent. Tumor recurrence was noted at a mean of 19 months postoperatively in 14 patients. Ninety-six patients received adjuvant postoperative radioiodine therapy to ablate residual functioning thyroid tissue or suspected metastases. We conclude that total thyroidectomy as treatment for differentiated thyroid carcinoma carries a low rate of morbidity, treats occult contralateral disease, and should facilitate radioiodine scanning and ablation of residual functioning thyroid tissue or metastatic disease. PMID- 8476140 TI - Bilateral neck exploration for primary hyperparathyroidism. AB - Controversy about the operative approach for primary hyperparathyroidism has prompted a review of our operative experience since 1980. We treated 73 patients with primary hyperparathyroidism during this 10-year period, all of whom underwent bilateral neck exploration in which the surgeons attempted to locate all parathyroid tissue. Thirty-eight patients (52%) were found to have a solitary adenoma, while 35 (48%) patients had multiple gland pathology. There were two cases of persistent hypercalcemia because of a synchronous parathyroid hormone secreting malignancy in one patient and aberrant fifth gland adenoma in the other patient. Without bilateral neck exploration, about one-half of the patients in our series would not have been cured of primary hyperparathyroidism. Because of the high incidence of multiple parathyroid gland involvement, we conclude that thorough bilateral neck exploration must be considered the goal for surgical treatment of primary hyperparathyroidism. PMID- 8476141 TI - Cause and current management of reoperative hyperparathyroidism. AB - We reviewed 137 cases of hyperparathyroidism followed for 6-72 months to determine the reasons for failure and to outline the successful management of reoperative hyperparathyroidism. Of 127 patients treated initially at Thomas Jefferson University Hospital, three required reoperation (2.4%) and 10 were referred with recurrent or persistent hyperparathyroidism. Reasons for failure were a missed gland in eight cases (62%), an ectopic gland in two cases (15%), supernumerary glands in two cases (15%), and malignant degeneration of an autotransplant in one case (8%). One patient had shortterm hypoparathyroidism requiring vitamin D supplementation (5.6%), but there were no injuries to the recurrent laryngeal nerves. We conclude that adequate knowledge of the location of normal and ectopic glands with meticulous search will reduce most reoperations, and, with identification of all four glands and routine cervical thymectomy in multigland disease, the rate should be less than 5 per cent. Patients requiring reoperation should undergo noninvasive localization studies and, if equivocal, selective venous sampling for parathyroid hormone. The major complication rate should be less than 10 per cent. PMID- 8476142 TI - Management of patients diagnosed as acute intestinal obstruction secondary to adhesions. AB - In an attempt to define an optimal strategy for managing small bowel obstruction secondary to adhesions, we reviewed 116 such cases encompassing a 5-year period at Hackensack Medical Center. Ninety-five patients underwent a trial of nonoperative treatment with a 35 per cent failure rate necessitating operation. This result was not influenced by the type of enteral tube used for decompression or predictable on the basis of initial clinical or laboratory findings. Significant complications occurred in those patients delayed more than 48 hours. The classic signs were poor indicators of strangulation. Patients with small bowel obstruction secondary to adhesions should be operated upon early (within 24 hours) but may be treated nonoperatively for 24 to 48 hours, provided that no signs of strangulation are present or develop. Failure to show improvement during this 48-hour period requires immediate operative intervention. The group as a whole would have benefited if early operation were done routinely. PMID- 8476143 TI - Shotgun wounds to the abdomen. AB - In 1963 Sherman and Parrish (Sherman RT, Parrish RA. Management of shotgun Injuries: A Review of 152 Cases. J Trauma 1963;3:76-86) classified shotgun wounds into three types based upon distance and penetration. Because distances are often unknown, we redefined Sherman's groups by pellet scatter. Type I patients had > 25 cm of scatter, Type II had < 25 cm but > 10 cm, and Type III had < 10 cm. Seventy-one abdominal shotgun wound patients were admitted over 8 years. Eight tangential wounds were managed by local wound care. Of the remaining 63, 27 were Type I, 10 were Type II, and 26 Type III. Two Type II and six Type III patients died within 24 hours. All required laparotomy. Nine of the Type I patients required laparotomy; eight had peritoneal signs and one had progressive abdominal tenderness, hypotension, and intra-abdominal pellets. Eighteen Type I patients without peritoneal signs were observed without complications. Type III patients suffered more vascular injuries and presented more frequently with hypotension than Type II patients. Of the patients surviving greater than 24 hours, Type IIIs received more transfusions and stayed longer in the intensive care unit and hospital than Type IIs. They also suffered more complications than Type IIs. Seven Type III patients required complicated reconstruction of the abdominal wall. Classification of abdominal shotgun injuries using pellet spread is a more useful system in determining patient management and prognosis compared to systems based on distance. Type II and III abdominal shotgun injuries require laparotomy, debridement of soft tissue injuries and frequently reconstruction of abdominal wall defects. Type I injuries can be managed effectively using signs of peritoneal irritation or progressive abdominal tenderness as the best indicator of the need for operation. PMID- 8476144 TI - Nonmalignant ectopic thyroid tissue. AB - Benign ectopic thyroid tissue is a rare entity. The etiology is related to the embryological development and maturation of the thyroid gland. It is important to consider metastatic thyroid carcinoma when ectopic thyroid tissue is identified. We present two cases of nonmalignant ectopic thyroid tissue. PMID- 8476145 TI - Acute acalculous cholecystitis following open heart surgery. AB - We undertook a retrospective study designed to ascertain the frequency of acute acalculous cholecystitis (AAC) following open heart surgery. In the study period 1982-1990, 22 of 6393 patients following open heart surgery were recognized to have developed AAC, an incidence of 0.34%. The majority of patients (16/22) presented within the first postoperative week. Vague right upper quadrant physical findings, nonspecific changes in the liver function chemistries and unexplained sepsis frequently led to radiologic evaluations. Ultrasonography was the most valuable radiologic study, with a diagnosis sensitivity of 82%. Technetium cholescintography can serve as a useful adjunct when interpreted in the context of other clinical findings. Cholecystectomy was performed in 20 patients and cholecystostomy in two. Nine (41%) patients had gangrenous gallbladders with frank perforation in two. A specific preoperative diagnosis was made in 19 patients (86%). Fifteen patients survived for a mortality rate of 32%. In 12 of 15 survivors (80%), the diagnosis of AAC was established and laparotomy performed within 48 hours of first clinical suspicion. Gangrene and perforation were seen in 87% of patients in whom surgery was delayed. AAC is a life threatening condition especially in critically ill patients. Experience suggests that early diagnosis and operative intervention are the key elements of treatment. Delay of operative management on the grounds of recent cardiac surgery is not justified. PMID- 8476146 TI - The role of endoscopic retrograde cholangiopancreatography: sphincterotomy versus common bile duct exploration as a primary technique in the management of choledocholithiasis. AB - 253 patients underwent diagnostic or therapeutic intervention for a presumed diagnosis of choledocholithiasis. In 104 (mean age, 60 years) the diagnosis was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) or common bile duct exploration (CBDE). Of this group, 70 patients first underwent a total of 102 attempts at endoscopic sphincterotomy (ERCP-S). Success (clearing the common duct of stones) was achieved in 43 patients (61%), though an average of 1.5 ERCP S/patient was required (maximum of four per patient). Of the 27 in whom ERCP-S failed, 20 went on to CBDE, which was successful in 18. Significant morbidity occurred in 12 (17%) ERCP-S patients, including hemorrhage. There were no deaths. Of the 34 patients who first underwent CBDE, 30 were cleared of common duct stones (88%). ERCP-S was subsequently employed to retrieve retained stones in three patients. Significant morbidity was documented in three (9%). No patients required perioperative blood transfusion. There were no deaths. While there is, as expected, a lower initial success rate with ERCP-S than with CBDE, the fact that ERCP-S is a less invasive procedure than is CBDE justifies its preferential utilization. However, patients must be informed that successful ERCP-S may require multiple visits to the endoscopy suite. Furthermore, the morbid consequences of ERCP-S, particularly hemorrhage, cannot be understated. PMID- 8476147 TI - Laparoscopic hernia repair: a preliminary report. AB - Advances in laparoscopic technique have provided the opportunity to perform preperitoneal herniorrhaphy and potentially avoid the morbidity associated with open techniques. From January 1991 to May 1992, two primary surgeons repaired 63 inguinal hernias (42 indirect, 20 direct, 1 femoral) on 48 patients using a standardized laparoscopic technique. The hernia defect was visualized laparoscopically, and the peritoneum anterior to the defect was incised. The hernia sac was dissected from the inguinal canal. The hernia defect was then loosely packed with rolled 1 x 6-inch polypropylene mesh (average number of rolls used was 3.4). A sheet of polypropylene mesh (average 5 x 8 cm) was then placed over the mesh rolls and the hernia defect and anchored with an endostapler. The peritoneum was closed over the mesh sheet with standard laparoscopic clips. There were 44 males and 4 females in the study group. The mean age was 55 years (range, 17-89 years). The mean follow-up was 5.8 months (range, 1-12 months). Thirty three patients underwent unilateral hernia repair, and 15 patients underwent bilateral hernia repair. Clinically unsuspected contralateral hernias were identified at the time of laparoscopy in seven patients. The mean duration of surgery was 118 minutes (range, 80-165 minutes) for bilateral hernia repair, and 70 minutes (range, 45-100 minutes) for unilateral hernia repair. All patients with laparoscopic hernia repairs were treated on a same-day or less-than-24-hour in-hospital stay. Complications were designated as minor, moderate, or severe. There were 14 minor complications, which included subcutaneous hematomas at the trocar site, scrotal ecchymosis, groin swelling emphysema, and testicular asymmetry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476148 TI - Delayed repair of congenital diaphragmatic hernia. AB - Early reports of improved survival in newborns with congenital diaphragmatic hernias (CDH) utilizing extracorporeal membrane oxygenation (ECMO) and/or a delayed repair (DR) approach have been tempered by recent failures to document such an improvement. We have used ECMO to salvage emergently repaired patients with CDH since January 1984. From January 1990 to January 1991, we treated 16 CDH patients with mechanical ventilation and other supportive techniques until persistent pulmonary hypertension of the newborn resolved. We compared this DR group to 19 patients emergently repaired from February 1987 to December 1989. Of the 19 emergently repaired patients, 16 had a best post ductal (BPD) PO2 > 50 mm Hg. Eight patients survived (42 per cent of all and 50 per cent of those with a BPD PO2 > 50). Thirteen required ECMO and six of these survived. Five of six ECMO survivors had significant ECMO complications, and ECMO was "inappropriately" performed on three of six nonsurvivors. Of the 16 DR patients, nine achieved a BPD PO2 > 50 mm Hg and seven survived (44 per cent of all and 78 per cent of those with a BPD PO2 > 50). Seven required ECMO and four of these survived. All survivors in both groups had a BPD PO2 > 90 mm Hg. Delayed repair did not improve survival statistics for CDH with early respiratory distress at our hospital but it has allowed stratification of potential survivors, fewer inappropriate ECMO cannulations, and many fewer ECMO complications. PMID- 8476149 TI - Retroperitoneal hematoma following femoral arterial catheterization: a serious and often fatal complication. AB - Retroperitoneal hematoma (RPH) following cardiac catheterization is an infrequent (0.15% incidence) but morbid complication. During a 13-month study period, 11 patients with a significant RPH requiring operative intervention were identified. The mean transfusion requirement was 8.7 units, with two deaths as a consequence of their RPH. Adjunctive cardiac procedures included percutaneous transluminal coronary angioplasty (five), stent placement (one), and thrombolysis (two). Two patients had RPH following aortography. Suspicion of RPH was most frequently prompted by a falling hematocrit (73%), with hypovolemic shock (systolic blood pressure < 90) in 64%. Lower quadrant or flank pain occurred in four patients. Lower extremity pain occurred in five patients due to femoral nerve compression. Of six patients with a preoperative femoral nerve palsy, complete resolution occurred in four cases. RPH following femoral arterial puncture is a cause of significant morbidity, particularly in the anticoagulated patient. Postcatheterization anticoagulation and high arterial puncture were the principal risk factors (p < 0.001). Early recognition is essential and should be prompted by a falling hematocrit, lower abdominal pain, or neurological changes in the lower extremity. There should be a low threshold for performing abdominopelvic CT scans in such patients. Management of RPH must be individualized: 1) patients with neurological deficits in the ipsilateral extremity require urgent decompression of the hematoma, 2) anticoagulation should be stopped or minimized, 3) hematoma progression by serial CT necessitates surgical evacuation and repair of the arterial puncture site. PMID- 8476150 TI - The medical legal implications of following mammographic breast masses. AB - Delay in breast cancer diagnosis continues to account for the highest percentage of medical malpractice cases in the United States. A retrospective, computer aided study was undertaken to investigate a number of parameters used in making medical-legal decisions in missed breast cancer cases. Over a 5-year period, 435 women with invasive breast cancers were registered at the Comprehensive University Breast Cancer Center. A close correlation between mammographic and final histologic size was verified (R = 0.74). In 5-mm increments, starting with a 1.0-mm tumor, there was an increasing percentage of positive nodes identified with increasing size of the tumor. Major percentage increases in frequency of positive nodes were noted at tumor sizes of 11 and 21 mm. This corresponded to an increasing number of recurrences and a decreasing 5-year disease-free survival (DFS) between consecutive 5-mm increments, although the differences were not significant. A multivariate regression analysis confirmed that the most important predictor of DFS was lymph node status (p = 0.0046) and not tumor size. After adjusting for lymph node status, tumor size was not significant. It is concluded that a period of observation, in which a breast cancer may increase in size is not substandard care since tumor size, after accounting for lymph node status is not significant at predicting DFS. PMID- 8476151 TI - Fournier's gangrene: historic (1764-1978) versus contemporary (1979-1988) differences in etiology and clinical importance. AB - Experience with 11 cases of Fournier's gangrene during the decade 1979-1988, prompted this review of the English language literature to determine whether there have been changes in demography, etiology, and outcome, as compared to cases dating to 1763. All cases were evaluated according to age, sex, bacteriology, etiology, and outcome. In the decade 1979-1988, 449 cases were reported. The average age of the patients was 49.8 years; with 14 per cent occurring in females. Synergistic polymicrobial infections were present in all cases. The most commonly reported etiologies were colorectal (33%), idiopathic (26%), and genitourinary (21%). Mortality associated with colorectal etiology was highest (33%, p < 0.05). Female mortality (49%) was not significantly greater than male mortality (17%), when obstetrical etiology was excluded. Overall mortality was 22%. Comparison with 386 cases of Fournier's gangrene reported between 1763 and 1978 reveals that the mean age of patients remains relatively low, and males continue to predominate. The pathophysiologic aspects of this disease appear similar in both sexes. The mortality rate from colorectal sources is significantly greater than from other common causes. Neither the introduction of antibiotics nor the development of newer ones has reduced mortality significantly. In spite of newer diagnostic techniques, the etiology remains unclear in over one-fourth of cases. PMID- 8476152 TI - The spleen and its vasculature in pancreatitis: CT findings. AB - The spleen and its vasculature are susceptible to damage from pancreatic inflammatory exudates. Fourteen patients were identified who demonstrated splenic or splenic vascular involvement from pancreatitis on computed tomography. Findings included intra- and perisplenic inflammatory fluid collections (n = 6), acute splenic hematomas (n = 3), splenic infarction (n = 1), splenic artery pseudoaneurysm (n = 1), and splenic vein thrombosis (n = 6). Eight of the 14 patients went on to urgent interventions including percutaneous catheter drainage (n = 2) and transcatheter embolotherapy (n = 6) based on the CT findings. PMID- 8476153 TI - Primary leiomyosarcoma of the greater omentum: case report and review of the literature. AB - Omental leiomyosarcomas are rare intra-abdominal tumors. This report describes a case of primary leiomyosarcoma of the greater omentum discovered on abdominal CT scan. The mass was removed via laparotomy and an omentectomy performed. At 2 years postoperatively there is no sign of tumor recurrence or metastasis. PMID- 8476154 TI - Necrotizing fasciitis secondary to discoid lupus erythematosus. AB - Necrotizing fasciitis (NF) is an uncommon, but devastating, disease with a significant morbidity and mortality, unchanged in the last several decades. This case report is the first successful management of a patient with NF secondary to discoid lupus erythematosus. A review of the literature describes current concepts of etiology, pathophysiology, diagnosis, and treatment of NF. This case report represents a growing class of patients at increased risk of NF due to iatrogenic immune compromise. PMID- 8476155 TI - Comparison of continuous single layer polypropylene anastomosis with double layer and stapled anastomoses in elective colon resections. AB - The documented leak rate of the continuous single layer polypropylene (CSLP) anastomosis in elective colon resection is 0-6 per cent. It is more cost effective than stapling (S), and should be faster and easier to perform than the double-layer (DL) technique. However, there have been no reported series comparing the outcome of the CSLP anastomosis with the DL and S techniques. We reviewed the charts of 100 patients with elective colon resections. Eighty-four had data sufficient for analysis. There were 44 CSLP, 21 DL, and 19 S. The groups were comparable with respect to 12 preoperative variables. Proportionately more large-small bowel anastomoses were performed in the S group, and no patient in the S group was actively taking steroids. Clinical outcome was assessed. All leaks were clinically apparent and documented with contrast enema or laparotomy. The leak rate for the CSLP was 6.8 per cent (3/44). Two of the three patients with leaks were taking steroids. There were two leaks in the DL group (9.5%), one of which was taking steroids, and no leaks in the S group. The difference in leak rate between the three groups was not statistically significant. The average cost for CSLP at our institution is $4.00 compared with $8.00 and $35.00 for the DL and S, respectively. We conclude that the CSLP is a reasonable and safe alternative to DL and S anastomoses. PMID- 8476156 TI - Primary papillary thyroid carcinoma presenting as cervical lymphadenopathy: the operative approach to the "lateral aberrant thyroid". AB - In contrast to a few follicles arranged in a wedge-shaped segment at the periphery of a lymph node, a significant amount of thyroid tissue in a cervical lymph node is considered evidence of metastatic thyroid carcinoma. In a consecutive series of 243 patients with papillary carcinomas, 52 presented with lateral cervical masses that proved to be lymph nodes with metastatic thyroid carcinoma, in the absence of readily palpable thyroid nodularity. The metastatic disease was demonstrated by excisional biopsy in 40 patients and fine needle aspiration cytology in 12 patients. Thirty-two (of the 52) underwent further diagnostic work-up, consisting of radionuclide scintigraphy and ultrasonography, with the demonstration of abnormalities consistent with a thyroid neoplasm in 75 per cent (24/32) of these patients. The remaining 20 patients had no additional studies except for chemical thyroid function evaluation. The operative treatment in all 52 patients was total thyroidectomy and unilateral or bilateral modified neck dissections, when extensive cervical adenopathy was encountered. Papillary thyroid carcinoma, ranging in size from 2 to 14 mm, was found in the lobe ipsilateral to the presenting cervical node metastasis, in all specimens. In addition, contralateral cervical lymph node metastases were found in five (10%) of these patients, with no evidence of thyroid carcinoma in the corresponding thyroid lobe. With a mean follow-up period of 9 years, all patients are alive with no evidence of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476157 TI - Recurrent hyperparathyroidism due to parathyroid autografts: incidence, presentation, and management. AB - Recurrent hyperparathyroidism (HPT) occurs in a small percentage of patients undergoing parathyroidectomy for primary HPT and is usually due to inadequate excision of hyperfunctioning parathyroid tissue in the neck, a missed ectopic and hyperplastic parathyroid, or, less commonly, parathyroid carcinoma and parathyroid autografts. In order to determine the incidence, clinical characteristics, and outcome of patients with recurrent HPT due to parathyroid autografts, we reviewed our experience with 604 consecutive patients operated on for primary HPT between 1965 and 1989. One hundred of these patients received parathyroid autografts consisting of portions of one or more parathyroid glands. Three patients with autografts, placed in the sternocleidomastoid muscle, developed recurrent HPT due to their autografts for an incidence of 3 per cent. Recurrent disease was diagnosed between 62 and 113 months with an average of 89 months. The autotransplants in all three of these patients were from hyperplastic or adenomatous parathyroid tissue. Two patients had a history of neck irradiation. Preoperative thallium scans accurately localized the hyperfunctioning parathyroid tissue in all three patients. At operation, the hyperfunctioning autografts had grown into a discrete mass with a single vascular pedicle and were resected. Histologic examination disclosed either hyperplastic or adenomatous tissue, and corresponded to the histology and location of the original tissue transplanted in each case. Follow-up ranges from 12 to 67 months, with an average of 48 months. All patients remain cured and none require oral calcium supplementation. We conclude that graft-dependent recurrent HPT is due to the autotransplantation of hyperplastic or adenomatous parathyroid tissue and that thallium scanning is instrumental for diagnosis and localization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476158 TI - Anastamoses and bifurcations of the recurrent laryngeal nerve--report of 1177 nerves visualized. AB - One thousand seventy-seven recurrent laryngeal nerves were observed in 719 patients. Seven hundred forty-seven nerves bifurcated or trifurcated over 0.5 cm inferior to the cricoid cartilage (63%). Of these, 170 patients had bilateral nerve bifurcations. Thirty-nine per cent of the patients had bilateral bifurcations when one side bifurcated. Eleven patients had direct laryngeal nerves, two of which bifurcated. Five of these 11 patients also had a recurrent and direct laryngeal nerve. Seven patients had recurrent laryngeal nerves, all on the right side, receiving branches directly from the vagus nerve 6-14 cm from the cricoid. Damage to any filaments to or from the recurrent laryngeal nerve can cause vocal cord paralysis. Damage to branches to the esophagus from the recurrent laryngeal nerve can cause dysphagia. PMID- 8476159 TI - Management of pulmonary blastoma in children. AB - Pulmonary blastoma is a rare neoplasm, accounting for 0.5 per cent of all primary malignant pulmonary tumors. The clinical features, radiologic findings, and management of five children with pulmonary blastoma are described. The female/male ratio was 4:1. Mean age at presentation was 34 months, with a mean duration of symptoms of 1.8 months. Fever and cough were the most common symptoms. Opacification of the right lung field with mediastinal shift to the left was the predominant roentgenologic feature. The tumor involved the right chest in all patients. Thoracotomy was performed in all patients to establish the diagnosis. Two patients underwent complete resection at the initial operation, an incomplete resection was performed in one patient. Delayed complete resection was performed in another patient. All the patients received combination chemotherapy and one patient also received radiotherapy for primary disease. Two patients with histologic and immunohistochemical evidence of striated muscle differentiation were treated as rhabdomyosarcomas. Both these patients have survived for 24 and 67 months after diagnosis. The tumor recurred in three patients. Recurrence was treated with a combination of surgery, chemotherapy, and radiotherapy. Overall disease-free survival rate was 40 per cent. Long-term follow-up and additional patients are required to provide prognostic information. PMID- 8476160 TI - Peliosis of the spleen: a rare cause of spontaneous splenic rupture with surgical implications. AB - Peliosis is a rare entity, formerly seen almost exclusively at autopsy, which most commonly involves the liver and less frequently the spleen. We present the sixth reported case of splenic peliosis discovered at surgical exploration and discuss the relevant findings and background of this condition, which may become an important issue for the surgeon. PMID- 8476161 TI - Pneumothorax in AIDS patients: operative management. AB - Acquired immunodeficiency syndrome (AIDS) is a devastating disease. Pneumocystis carinii pneumonia (PCP) is a major clinical manifestation of AIDS. A 2-year experience with eight operations for PCP-associated pneumothorax in seven AIDS patients was reviewed. Initial treatment was tube thoracostomy in all cases. Operation was performed because of inability to expand the lung and/or persistent air-leak. Time from insertion of the initial chest tube to operation was 9-66 days (mean, 33 days). Pulmonary air leaks were closed with surgical staples and/or sutures. Chest tubes were removed 3-16 days after surgery (mean, 8.5 days). There were no cases of postoperative respiratory insufficiency and there were no deaths. Patients were discharged from the hospital 6-18 days after surgery (mean, 13 days). The postoperative hospital stay was substantially shorter than the preoperative period of nonoperative therapy (13 vs. 33 days). Follow-up is complete in six of the seven patients. Three patients died of AIDS 4 8 months after surgery (mean, 6 months). Three patients are alive 7-14 months after operation (mean, 11 months). Operative management of PCP-associated pneumothorax is effective and can be performed with low morbidity and mortality. We conclude that surgery should be considered as an early option in AIDS patients with PCP-associated pneumothorax. PMID- 8476162 TI - Endoscopic tattooing of the colon: clinical experience. AB - Nonpalpable lesions of the colon can be difficult to locate intraoperatively. We have demonstrated in an experimental study in dogs that the colon can be endoscopically "tattooed" by injecting dye through a flexible needle into the wall of the colon. At laparotomy, the resulting "tattoo" is then visible on the serosal surface of the bowel. This technique allows precise surgical localization of endoscopically identified lesions simply by visualizing the dye. Our initial clinical experience tattooing 15 colonic lesions in 12 patients is presented. In all patients, the endoscopically injected dye (1 per cent indocyanine green) was easily visualized on the serosal surface of the colon at surgery. The dye remained at the site of injection for at least 36 hours allowing tattooing to be performed the day before surgery. No significant complications were encountered with only one patient developing an inflammatory reaction at the site of injection. This experience demonstrates the clinical utility of endoscopic tattooing of the colon to permit accurate intraoperative localization of small or nonpalpable lesions. PMID- 8476163 TI - Ambulatory pH monitoring in the management of reflux. AB - Ambulatory pH monitoring is a useful tool in the diagnosis and treatment of different esophageal and pharyngeal complaints. We have studied its use in an office setting in 15 patients with suspected gastroesophageal reflux disease (GERD). The patients were monitored for at least 18 hours while wearing a two channel probe at home. Data obtained confirmed severe GERD in 6 patients and chest pain without GERD in 2 patients. Two patients continued to have symptoms in spite of appropriate therapy, while 2 untreated patients had symptoms of GERD with normal pH studies. We feel this technique is relatively safe and cost effective and causes minimal disruption of the patient's life-style, while enabling the physician to monitor therapy and help achieve a good therapeutic outcome. PMID- 8476164 TI - Auricular cartilage grafts in laryngotracheal reconstruction. AB - Introduction of the anterior cricoid split (decompression) and laryngotracheal reconstruction with costal cartilage graft has resulted in the successful management of many cases of subglottic stenosis. However, the procedure does not allow uniform extubation, and laryngotracheal reconstruction with costal cartilage may be too aggressive for neonates. We have explored the use of autogenous auricular cartilage graft in laryngotracheal reconstruction. Its high rate of success and low morbidity have enabled us to expand the indications. We report our experience in 23 patients with auricular cartilage grafts. PMID- 8476165 TI - Stroboscopic videolaryngoscopy: a comparison of fiberscopic and telescopic documentation. AB - The clinical value of stroboscopic videolaryngoscopy (SVL) for the evaluation of laryngeal disorders has been emphasized. Some investigators advocate the use of a flexible fiberscope, while others recommend the use of a rigid telescope for SVL. In order to determine which procedure is more useful for clinical diagnosis, the senior author (E.Y.) performed both fiberscopic and telescopic SVL on 120 consecutive patients who complained of hoarseness. Equipment used included the Olympus ENF-P3 fiberscope, the Nagashima SFT-1 rigid telescope, the Nagashima LS 3A laryngostroboscope, and color video cameras. Our study indicated that stroboscopic images produced by telescopic SVL were superior to those from fiberscopic SVL in the majority of cases. The purpose of this paper is to compare fiberscopic and telescopic SVL, to evaluate the advantages and disadvantages of fiberscopic and telescopic SVL, and to present the authors' recommendations. PMID- 8476166 TI - Rigid bronchoscopy balloon catheter dilation for bronchial stenosis in infants. AB - Stenosis of the tracheobronchial tree can be a life-threatening problem. Management options for symptomatic stenosis include serial dilation, cryotherapy, laser resection, and open surgical correction. Recently, balloon angioplasty catheters have been used to dilate stenotic airway segments. The experience in infants is limited and has for the most part utilized guide wires and fluoroscopy for balloon placement. We present two infants with symptomatic bronchial stenosis who underwent endoscopic angioplasty balloon catheter dilation. Operative technique involved catheter placement under direct vision with a rigid bronchoscope. Catheters (6F) with 8-mm-diameter balloons were used. Balloon expansion was controlled with a hand-held manometer. Both infants demonstrated significant lumen size improvement intraoperatively and marked clinical improvement postoperatively, substantiated by endoscopy and radiographs. One infant has required one repeat dilation and has subsequently been asymptomatic. The other infant has had no further respiratory problems. Our technique, using a rigid bronchoscope with direct visualization of catheter placement, obviates the need for guide wires and C-arm fluoroscopy as previously described. Endoscopic placement enables direct visualization of balloon position, and fine adjustments are possible if further dilation is necessary. Rigid bronchoscopic balloon catheter dilation can be a successful technique for bronchial stenosis and should be considered prior to attempting more invasive surgical correction. PMID- 8476167 TI - Eighteenth Daniel C. Baker, JR, Memorial Lecture. Art and science of laryngeal photography. AB - Photography of the pharynx, larynx, and trachea has exercised the ingenuity of laryngologists and photographers for 100 years. There have been many successful methods. The most reliable and versatile modern system uses a 35-mm single frame, single lens reflex camera with Hopkins telescopes and a synchronized, automatic exposure, computer-controlled, remote electronic flash generator. The technique described, which has been used by the author for many years, not only allows excellent visualization and reliable documentation, but yields consistently reproducible photographs under all conditions. PMID- 8476168 TI - Teflon injection: pointers and pitfalls. AB - Our objective is to clarify the procedure used in a series of 335 cases of injection of paralyzed vocal cords. Over 29 years, questions have arisen about the procedure, mostly from trainees. They relate to timing, indications, method, and follow-up. Results of the procedure, when properly performed, have been highly successful. Where indications are appropriate, injection is usually uncomplicated, relatively safe, and done with minimum instrumentation. This is our response, in a question-and-answer format, to the most frequent queries. PMID- 8476169 TI - Pendred's syndrome. AB - Although 5% of all cases of congenital deafness are caused by Pendred's syndrome, there are few reports in the literature. Seven patients with Pendred's syndrome in three families living in the same village were detected. For that reason, the syndrome is reviewed in light of the literature. The sex distribution of the patients with Pendred's syndrome and their families was recorded. We tested for thyroxine, triiodothyronine, thyroid-stimulating hormone, triiodothyronine resin uptake, and perchlorate, and performed caloric testing. In one patient, subtotal thyroidectomy was performed. In the histopathologic study, a thyroid nodule filled with colloid was found. Chromosome studies showed no anomalies in any patient. Five of the patients were deaf-mutes. We observed that the parents were cousins in all three families. These families also had healthy children, and the existence of the syndrome in both sexes points to an autosomal recessive trait. PMID- 8476170 TI - Comparison of functional endoscopic sinus surgery under local and general anesthesia. AB - We present a retrospective comparison of intravenous sedation and general anesthesia techniques employed at New York University-Bellevue Medical Center for functional endoscopic sinus surgery. Some authors have stressed the use of local anesthesia with intravenous sedation in order to avoid complications and reduce blood loss. We have reviewed 232 patients who underwent 401 consecutive ethmoidectomies and maxillary antrostomies. Local anesthesia, employed in 64% of patients, carried an estimated blood loss of 23 mL per side. General anesthesia was associated with an average blood loss of 58 mL per side. The rate of operative complications for local anesthesia was 8.7% per patient, with a 1.6% rate of major complications per side. General anesthesia carried an overall complication rate of 2.4% per patient, with no major complications. General anesthesia is a relatively safe and viable option for endoscopic sinus surgery that in selected cases may be preferable to local anesthesia. PMID- 8476171 TI - Aerodynamic assessment of the speech of adults undergoing multichannel cochlear implantation. AB - This investigation was designed to evaluate the aerodynamic characteristics of the speech of adult multichannel cochlear implant (Nucleus, 21-channel) recipients. Five adults with an acquired profound sensorineural hearing loss were tested before implantation, immediately following implantation, and 3, 6, 9, and 12 months after implantation. A commercially available computerized pressure-flow instrumentation system was employed to assess the respiratory, laryngeal, velopharyngeal, and oral articulatory subsystems of speech of the implantees. The results of the investigation indicated 1) a slight increase in airflow rate values for sustained vowel /a/phonation after implantation, 2) a slight increase in duration of sustained vowel phonation from the preimplant period to the last postimplant period, 3) an increase in laryngeal airway resistance after implantation that resulted from a larger increase in estimated transglottal pressure than in transglottal airflow, 4) maintenance of normal velopharyngeal closure in oral-nasal contrastive contexts, and 5) slight increases in oral orifice area for fricative syllable utterances following implantation. Individual strategies for coordinated control of the speech mechanism appear to be potent variables to consider when assessing speech production. PMID- 8476172 TI - Angiolymphoid hyperplasia with eosinophilia (histiocytoid hemangioma): evaluation of treatment options. AB - Angiolymphoid hyperplasia with eosinophilia is an uncommon benign vascular proliferative lesion of unknown cause. In this report, a case is presented of a patient who was confirmed to be positive for human immunodeficiency virus and in whom the lesion had shown rapid accelerated growth. The case is used to illustrate a variety of therapeutic techniques and to evaluate the effectiveness of the various alternatives in the treatment of this unusual clinical problem. Long-term follow-up after radical excision of the tumor mass is presented. PMID- 8476173 TI - Effects of nasal allergen challenge on dynamic viscoelasticity of nasal mucus. AB - The effects of nasal provocation on the rheologic properties of nasal mucus were investigated in patients with allergic rhinitis provoked by house dust. The elastic modulus (G') and the dynamic viscosity (eta') of nasal mucus were determined by an oscillating sphere magnetic rheometer. Before and after the allergen challenge, G' increased, whereas eta' decreased with increasing oscillatory frequency; these findings indicate that the nasal mucus under these conditions is a non-newtonian fluid and has the cross-linked gel-like nature typical of mucus. Both G' and eta' values after nasal provocation were significantly lower than before. The values of G' and eta' after allergen challenge were in the optimal viscoelasticity range for mucociliary transport. PMID- 8476174 TI - Lymphoma of the sphenoid sinus presenting as an expansile mass. PMID- 8476175 TI - Peripheral epithelial odontogenic tumors. AB - Peripheral epithelial odontogenic tumors are the extraosseous equivalents of the much more often encountered central gnathic odontogenic tumors. The peripheral tumors arise in the mandibular or maxillary gingiva from the surface mucosa or dental lamina rests in the submucosa. Ameloblastoma is the most common histologic type. It, like all other peripheral epithelial odontogenic tumors, follows a benign, nonaggressive clinical course. PMID- 8476177 TI - Epidemiology and oral manifestations of HIV infection. PMID- 8476176 TI - Lengthening of congenital limb length discrepancy using callotasis: early experience of the Hospital for Sick Children. AB - Seventeen patients were reviewed after callotasis lengthening for congenital limb length discrepancy. The average age at lengthening was 10.8 years. Length discrepancy before lengthening ranged from 4.5 cm to 12 cm for the leg, and 24 mm to 30 mm for the forearm. At completion of the lengthening process, all but one patient had their discrepancy corrected successfully. The difficulties encountered were classified into problems, obstacles and complications. All patients suffered from superficial infection, but in only one case did this become a complication, resulting in a residual femoral discrepancy of 2 cm. Of the other three patients who suffered a complication, one fractured through the newly formed bone. The fracture was treated conservatively. In two further femoral lengthenings, the fixator had to be exchanged under general anaesthesia because it had reached its maximum excursion. Callotasis appears to be a safe and reliable method for correcting congenital limb length discrepancy in children. PMID- 8476178 TI - Surgical audit without autopsy: tales of the unexpected. AB - To establish our current practice and the potential value of the autopsy in general surgery, a retrospective review of general surgical autopsies was performed at one district general hospital from January 1989 to August 1991. There was considerable interconsultant variation in autopsy practice with a low 25% overall autopsy rate reflecting a low autopsy request rate. There were discrepancies between the clinical and pathological cause of death in 40 (63%) cases. There were important discrepancies which may have changed management in life in 18 (28%) autopsies, 7 (39%) of which were untreated visceral perforations. Autopsy is an important part of the surgical audit and will disclose considerable unsuspected pathology. Present autopsy rates are low and need to be improved. The unexpected finding of seven untreated visceral perforations requires further study. PMID- 8476179 TI - Strap muscles in thyroid surgery: to cut or not to cut? PMID- 8476180 TI - General surgeons' attitudes to the treatment and prevention of abdominal adhesions. AB - A questionnaire survey of general surgeons was undertaken to estimate the incidence of abdominal adhesions as a clinical problem and to establish current attitudes to the treatment of adhesional bowel obstruction and the prevention of adhesion formation. Replies were received from 362 of 416 surgeons (response rate 87%). In all, 76% (95% confidence limits, 72%-80%) of surgeons operate upon at least two patients each year with adhesional small bowel obstruction and 31% (26 36) operate upon more than five patients. More than five patients are admitted each year with suspected adhesional bowel obstruction by 64% (59-69) of surgeons and 35% (30-40) of surgeons found adhesions to be a problem during a non-adhesion related laparotomy in more than five patients each year. This represents an estimated annual incidence of between 12,000 and 14,000 adhesion-related clinical problems in the United Kingdom. A number of preventive measures, such as the wearing of starch-free gloves (78% of surgeons; 95% CL 74%-82%), peritoneal lavage (68%; 63-73) and placement of the omentum beneath the wound closure (90%; 87-93) are generally accepted, whereas routine wetting of swabs (39%; 34-44) and the role of non-essential adhesiolysis (49%; 44-54) are controversial. Routine small bowel plication (1%; 0-2) and intubation (2%; 0-5) are rarely used. This survey gives an indication of the large burden on patients and the health services caused by abdominal adhesions, and demonstrates surgeons' wide variety of approaches to both the treatment and prevention of adhesion formation. PMID- 8476181 TI - Gastrointestinal disruption and vertebral fracture associated with the use of seat belts. AB - Seat belts have been shown to be beneficial in reducing the type and severity of injuries sustained in road traffic accidents. The association of vertebral and visceral injuries, although previously described, is rare. This and various other confounding factors may make diagnosis of the visceral injury difficult. We describe four cases of combined vertebral and visceral injury caused by the use of seat belts. The pathogenesis of the injury and subsequent management are discussed. PMID- 8476182 TI - 'Diabetic tibial disease': the case for revascularisation. AB - Diabetic patients with critical ischaemia of the lower limb are frequently considered to have unreconstructable vascular disease. In the presence of a palpable popliteal pulse they are often labelled as having 'small vessel disease'. In nine patients (mean age 69 years) with 'diabetic tibial disease' and critical ischaemia we have avoided major amputation using short vein bypasses. All revascularisations remained patent at a mean follow-up of 32 months (range 12 60 months). Diabetic patients with critical ischaemia should at the very least undergo arteriography to ensure that the possibility of successful distal revascularisation is not feasible before amputation is performed. However, if arteriography fails to demonstrate patent distal vessels and limb salvage is considered practical, Doppler insonation of the tibial and pedal vessels should be performed. PMID- 8476183 TI - Fractures of the sternal body. PMID- 8476184 TI - Fractures of the sternal body. PMID- 8476185 TI - A prospective comparison of laparoscopic versus open cholecystectomy. PMID- 8476186 TI - A prospective comparison of laparoscopic versus open cholecystectomy. PMID- 8476187 TI - The value of water-soluble contrast radiology in the management of acute small bowel obstruction. PMID- 8476188 TI - The value of water-soluble contrast radiology in the management of acute small bowel obstruction. PMID- 8476189 TI - The NHS reforms so far. PMID- 8476191 TI - Breast disease and the general surgeon. II. Effect of audit on the referral of patients with breast problems. AB - OBJECTIVES: To determine the number of patients with breast problems referred to general surgical clinics in a district general hospital and to assess the effect of changes implemented following the previous study on waiting time, investigations performed, and management of the patients. DESIGN: Two prospective outpatient audits with patient details recorded on questionnaires by the medical staff. SETTING: The general surgical outpatient clinics of a single general surgical firm at Newbury District Hospital, Berkshire. PATIENTS: Those patients attending the above clinics during two 3-month periods, 1 October to 31 December 1989 (Study 1), and 16 April to 19 July 1990 (Study 2). RESULTS: Of new referrals, 25% were for a breast problem. The waiting time fell from a median of 22 days in Study 1 to 10 days in Study 2. There was no significant difference between the studies for the proportion of each type of investigation performed. Between 80% and 85% of new patients did not need admission for an operation; however, of those operations performed, 65% were for carcinoma. The number of patients diagnosed as having carcinoma was the same in the two studies. CONCLUSIONS: That 25% of new, and up to 40% of follow-up patients seen in a general surgical clinic have breast problems. Many patients do not regard their symptoms as worrying and will not attend early clinic appointments even if these are offered. Writing to patients and general practitioners with the results of investigations ensures quicker receipt of the diagnosis and treatment plan, and reduces follow-up attendance. Only 15-20% of new patients need admission for an operation, and carcinoma is found in only 13-17%. Open access to the clinics does not result in general practitioners referring patients unnecessarily with breast problems. PMID- 8476190 TI - Breast disease and the general surgeon. I. Referral of patients with breast problems. AB - OBJECTIVES: To determine the proportion of all new and follow-up patients referred to general surgical outpatient clinics with breast problems. To ascertain how long these patients wait for an appointment and how many require investigation or admission for operation. To review our management of patients with breast problems in the clinic and to determine the ratio of benign breast disease to malignancy. DESIGN: A 3-month prospective outpatient survey with patient details recorded on questionnaires completed by the medical staff. SETTING: The general surgical outpatient clinics of this firm at Battle Hospital, Reading, and Newbury District Hospital, Berkshire. PATIENTS: Those patients attending the above clinics during the 3-month period 1 October to 31 December 1989. RESULTS: In all, 693 new patients and 554 follow-up patients were seen. Of the new patients, 119, and of the follow-up patients 140 were seen for a breast complaint. At Battle Hospital 16% of all new patients presented with a breast problem, while at Newbury Hospital the figure was 24%. Of the follow-up patients at Battle Hospital, 23% were seen for a breast problem, and 41% at Newbury. The overall median waiting time for a new outpatient appointment was 21 days. No investigations were needed in 22% of the patients. The remaining 93 patients had investigations and a total of 70 mammograms and 53 fine needle aspirations for cytology were performed. The mean cost of investigations per patient investigated was estimated at 27 pounds. Of new patients, 58% were discharged from the clinic after a single consultation, and investigations as necessary. In 79% of the patients admitted for an operation, the decision to admit was made on the basis of the initial history and examination alone. Of new patients, 84% did not need admission and were managed in the clinic. In all, 14 breast carcinomas were diagnosed--12% of new patients with breast problems. CONCLUSIONS: The figures suggest that 24% of new patients and 41% of follow-up patients attending a general surgical clinic are seen for a breast problem. The waiting time for new appointments is unacceptably long. Most new patients do not require admission for an operation. Only 12% of new patients referred with a breast problem were found to have a carcinoma. PMID- 8476192 TI - Splenic cysts: changes in diagnosis, treatment and aetiological concepts. AB - Splenic cysts are generally considered as either true epidermoid cysts or false pseudocysts. The former are thought to be congenital while the latter are reputedly post-traumatic. However, a number of important features are common to both types of cysts and this classification may need revision. The recognition of the importance of the spleen, together with developments in imaging and operative surgery have led to significant changes in the management of splenic cysts. Accurate preoperative diagnosis and localisation together with increasing awareness of splenic conservation techniques should now ensure that, whenever possible, cysts can be eradicated without resort to total splenectomy. We present four patients who illustrate various aspects of this condition. PMID- 8476193 TI - The Angelchik prosthesis behaves as a fundoplication. AB - It is not known why the Angelchik prosthesis prevents gastro-oesophageal reflux. A review of 53 barium meal examinations in 39 patients with the prosthesis showed that in 43 examinations the prosthesis was below the diaphragm. In 38 of these a small knuckle of stomach had herniated through the prosthetic ring alongside the oesophagus, forming a small intra-abdominal para-oesophageal hernia. Radiological reflux occurred in only one patient with such a hernia. In the remaining five examinations where the prosthesis was correctly situated in the abdomen, there was no hernia within the prosthetic ring and reflux occurred in three. In ten examinations the prosthesis had migrated into the mediastinum. None of these showed a hernia and reflux occurred in eight. It is suggested that the Angelchik prosthesis results in the formation of a small para-oesophageal hernia within a loosely fitting ring within the abdomen and this is a requirement for the success of the Angelchik prosthesis. Radiographically the intra-abdominal para oesophageal hernia inside the prosthesis results in buttressing of the intra abdominal oesophagus in a manner similar to a fundoplication. PMID- 8476194 TI - The use of Coca-Cola in the management of bolus obstruction in benign oesophageal stricture. AB - Oesophageal stricture is a complication of oesophageal reflux and may itself be complicated by bolus obstruction. We reviewed the records of patients presenting with dysphagia and who were found to have benign oesophageal strictures. We studied the outcome of bolus obstruction in 13 episodes affecting eight patients. In six episodes Coca-Cola was administered on the day before endoscopy, and in all these patients the bolus had cleared. In seven episodes nothing was administered before endoscopy, and in all seven a bolus was evident at endoscopy. In five of these seven the bolus was removed piecemeal and in each of these instances the endoscope had to be passed between two and five times. In the remaining two instances the procedure was abandoned and the patients returned to the ward for the administration of Coca-Cola. At subsequent endoscopy these patients were found to be clear of any bolus. These results suggest that the administration of Coca-Cola (or other aerated drinks) may clear a bolus in the acutely obstructed oesophagus. PMID- 8476196 TI - Opportunities for research in surgical training. PMID- 8476195 TI - Surgical discharge summaries: improving the record. AB - The problem area of communication between hospital and general practitioners may potentially be improved by the advent of new information technology. The introduction of a regional computer database for general surgery allows the rapid automated production of discharge summaries and has provided us with the opportunity for auditing the quality of old and new styles of discharge communication. A total of 118 general practitioners were sent a postal questionnaire to establish their views on the relative importance of various aspects of patient information and management after discharge. A high response rate (97%) indicated the interest of general practitioners in this topic. The majority (73%) believed that summaries should be delayed no more than 3 days. The structured and shortened new format was preferred to the older style of discharge summary. The older format rarely arrived within an appropriate time and its content was often felt to be either inadequate (35%) or excessive (7%) compared with the new format (8% and 1%, respectively). The diagnosis, information given to the patient, clinic date, list of medications and investigations were considered the more important details in the summary. Improvements in the discharge information were suggested and have subsequently been incorporated in our discharge policy. The use of new information technology, intended to facilitate clinical audit, has improved our ability to generate prompt, well structured discharge summaries which are accepted by the general practitioners. PMID- 8476197 TI - The organisation of general surgery services in a population. PMID- 8476198 TI - Localization of the alpha 3 beta 1 integrin in some common epithelial tumors of the ovary and in normal equivalents. AB - Monoclonal antibodies (mAbs) against cultured human ovary carcinoma cells were produced. We obtained 7 mAbs which reacted diffusely with carcinoma of the ovary but only weakly with vessels and the surface epithelial layer of normal ovary. Biochemical characterization of these mAbs indicated that 3 out of 7 were specific for the alpha 3 chain of the Vla-3 integrin, a receptor for fibronectin, collagen and laminin. Using one of these mAbs, we have studied, by immunohistochemical methods, the distribution of alpha 3 beta 1 integrin in mucinous, serous and endometrioid cystoadenocarcinoma of the ovary and in their normal equivalent: endocervical, tubal and endometrial epithelia. The results show that alpha 3 beta 1 is present in cell-cell contact areas and more abundantly at the junction between epithelial cells and basement membrane in endocervical, tubal epithelia, in epithelium lining the cavity of the uterus and in surface epithelium of the ovary. However, endometrial glands showed only weak and fragmented positivity at the basal pole of the cells. 26 out of 31 ovarian cancers studied, expressed the alpha 3 beta 1 integrin. However, basal localization, typical of normal epithelia, is not prominent or disappears in tumors and is replaced by a more diffuse reaction with variable immunohistochemical staining of the neoplastic cells. Furthermore, a comparative analysis of the expression of alpha 3 beta 1 and its ligands, laminin (LM), fibronectin (FN) and collagen IV (Coll IV), demonstrated that basal polarization of Vla-3 was always correlated with the presence of laminin and Coll IV, intrinsic components of the basement membranes. PMID- 8476199 TI - Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. II. Synergism with combined chemotherapy action. AB - The growth inhibitory effects of a combined application of sodium ascorbate (Vitamin C) and 2-methyl-1,4-naphthoquinone (Vitamin K3) together with various chemotherapeutic agents has been examined on in vitro cultured human endometrial adenocarcinoma (AN3CA) cells. Combined vitamin treatment and chemotherapy in well defined conditions of cell confluence and at the dose levels applied result in a synergistic effect on growth inhibition. The combined vitamins when reaching their own synergistic cytotoxicity levels frequently obscure the additional synergistic effects attributable to the chemotherapeutic agents. Apart from the specific cytotoxic characteristics of the chemotherapeutic drugs examined, the formation of reactive oxygen radicals during treatment, possibly accentuated by less defined secondary mechanisms, appears essentially responsible for the observed stimulated cytotoxicity. PMID- 8476200 TI - Antimetastatic activity induced by Clostridium butyricum and characterization of effector cells. AB - The effects of a bacterial vaccine, heat-killed Clostridium butyricum MII 588 cells, on the metastasis of B16-F10 melanoma in BDF1 mice was investigated. The vaccine stimulated natural killer (NK) cell cytotoxic activity against YAC-1 target cells, which peaked at 72 hr after the pretreatment, whereas maximum macrophage cytotoxic activity was obtained on days 9 to 11. These stimulated cytotoxic activities were also observed in B16-F10 tumor-bearing BDF1 mice. The important role of stimulated NK cells and/or macrophage in the antimetastatic effect was confirmed using Anti-asialo GM1 antibody, whole body x-ray irradiation and carrageenan treatment. In addition, the vaccine could induce a high titer of interferon-gamma (IFN-gamma), an important lymphokine which may account for a significant portion of its antimetastatic activity. PMID- 8476201 TI - Chromosomal changes and correspondingly altered proto-oncogene expression in human gliomas. Value of combined cytogenetic and molecular genetic analysis. AB - A combined cytogenetic and molecular genetic study was performed to analyze seven primary brain tumors: one oligoastrocytoma WHO-grade II, one anaplastic astrocytoma grade III, one anaplastic astrocytoma grade III/IV and four glioblastomas by G-banding and RNA dot blotting. A normal karyotype was found in the oligoastrocytoma. One of the two anaplastic astrocytomas (male) contained cells with a normal karyotype and cells with a Y-chromosomal loss, and the other one showed structural abnormalities too complex for complete analysis in mostly polyploid cells. Two of the four glioblastomas had few and the other two multiple chromosomal changes such as +7, +20, -8, -9 del(9)(p21), -10, del(10)(q24), 13,14, del(17)(p21), -22, add(3)(q13), double minutes and marker chromosomes. Compared to normal brain, all tumors had an increased EGFr and both anaplastic astrocytomas as well as three glioblastomas a decreased H-ras expression. The two glioblastomas with multiple chromosomal changes showed increased EGFr, Ki-ras, myb, mos and myc, decreased H-ras and N-ras and unchanged levels of abl, src and sis. Both the cytogenetic and molecular genetic findings are compatible even in the case of chromosomal losses, where the genes on the remaining allele may be responsible for dominant gene regulation mechanisms which result in a protooncogene overexpression. Our findings indicate that, apart from proto oncogene overexpression, other mechanisms, e.g. tumor suppressor gene inactivation, are important for glial tumorigenesis. Karyotypic analysis makes it possible to search specifically for genetic events still unknown but arising from particular chromosomal changes. PMID- 8476202 TI - Detection of DNA polymerase-beta gene expression by competitive polymerase chain reaction in human ovarian carcinoma cells. AB - The reliability of the competitive polymerase chain reaction (competitive PCR) for the detection and quantitation of gene expression in small tumor samples was evaluated. DNA polymerase-beta gene expression was detected in human ovarian cancer cell lines displaying a different degree of cisplatin resistance. The level of DNA polymerase-beta cDNA in the resistant cell line was threefold that of the parental sensitive line. Our results indicate that competitive PCR is a reproducible and sensitive method to detect differences in gene expression in small samples and open the possibility of using this approach to detect DNA polymerase beta cDNA in small samples from clinical tumors. PMID- 8476203 TI - Complete regression of advanced liposarcoma of the anterior chest wall with interferon-alpha and tumor necrosis factor-alpha. AB - This paper reports a case of complete regression of a liposarcoma in a 62-year old Japanese man who, in August 1986, presented with a giant subcutaneous tumor of the right anterior chest wall. Local radiotherapy and conventional chemotherapy were initially performed; however, the tumor did not respond at all. He then received cytokine treatment (interferon-alpha and tumor necrosis factor alpha). Nineteen months after cytokine treatment, the mass disappeared totally. The patient has been in complete remission for five years without recurrence and with no additional treatment. This suggests that the use of interferon-alpha and tumor necrosis factor-alpha in combination may be an effective and promising modality for liposarcomas which are refractory to the conventional anticancer treatments. PMID- 8476204 TI - In vitro cytotoxicity and differential cellular sensitivity of new N-methyl and N propargyl urea and nitrosourea derivatives of diamino acids against sixty human NCI tumor cell lines. AB - The in vitro cytotoxicity and differential cellular sensitivity of a series of new N-methyl and N-propargyl urea and nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. These compounds have a level of cytotoxic activity comparable to BCNU, CCNU and Methyl-CCNU. In this series of diamino acid derivatives, the N-nitroso group does not seems to be essential to the in vitro activity of these compounds. The N Propargyl derivatives have shown significantly more differential cellular sensitivity than the N-Methyl derivatives. Hence, the N-Propargyl group seems to induce more cell line specificity in our compounds. Based on their in vitro cytotoxic activity and mostly their pattern of differential cellular sensitivity, two compounds described in this work have been selected by the NCI for further development. These compounds are currently being screened in animal models. PMID- 8476206 TI - Glyoxalase activities in human tumour cell lines in vitro. AB - The activities of glyoxalase I (EC 4.4.1.5) and glyoxalase II (EC 3.1.2.6) were measured in 3 human non-malignant and 28 tumour cell lines. The activity of glyoxalase I was in the range 321-8751 mUnits/mg of protein. The glyoxalase I/glyoxalase II activity ratio was in the range 7-147; glyoxalase I activity was always markedly greater than glyoxalase activity. There was no significant difference between glyoxalase activities in non-malignant and tumour cell lines. The activity of glyoxalase I was within and above the range found in normal human tissues and the activity of glyoxalase II was within the range and below that found in normal human tissues. PMID- 8476205 TI - Butyramide and monobutyrin: growth inhibitory and differentiating agents. AB - Butyramide and monobutyrin were chosen for study as neutral compounds that might exhibit some of the growth inhibitory and differentiating effects of butyrate. Inhibitory effects on DNA synthesis in hepatoma cells and on cellular proliferation in mouse erythroleukemia cells were observed. Induction of differentiation by butyramide and monobutyrin was seen in mouse erythroleukemia cells as monitored by increased synthesis of hemoglobin and H1 zero histone. Butyramide and monobutyrin were less effective inducers of hemoglobin synthesis than butyrate but their neutral character may offer an advantage in the induction of tumor cell differentiation. PMID- 8476207 TI - Ag-NORs related to flow cytometry, morphometry and prognosis in patients with pancreatic cancer. AB - The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and that the number of Ag-NORs predicts survival. PMID- 8476208 TI - Growth inhibitory activity of S12363, a novel vinca alkaloid derivative on human melanoma cell lines. AB - The growth inhibitory activity of S12363, a new antineoplastic agent which belongs to the vinca alkaloid group incorporating an amino-phosphonate (bioester of valine), was studied on six human melanoma cell lines with different phenotypic characteristics and in vitro growth rates. S12363 was compared with vinblastine (VBL), vincristine (VCR) and vindesine (VDS) using the MTT assay. Inhibition was time- and dose-dependent. Overall, IC50 values ranged from 24 6770nM and 4.6-11.6 nM for the reference drugs and for S12363 respectively, after exposure for 1 hr. All the vinca alkaloids were more active when cells were exposed continuously for 72 hrs, inhibition by S12363 was greater than the reference drugs (p < 0.05 in 15/18 comparisons). The activities of VDS and S12363 were also compared using the clonogenic assay. IC50 values ranged from 45-500 nM and 17-75 nM respectively. On a molar basis, S12363 was significantly more active than VDS (ANOVA p < 0.0001). The shape of the cell survival curve obtained with S12363 was exponential, whereas that of VDS was of the exponential-plateau type. Furthermore, survival with higher concentrations of S12363 was inversely related to cells seeded. Cell cycle analysis showed these compounds to block cells in G2+M after exposure to their respective IC50 concentrations for 1 hr. This effect was obtained using a lower S12363 concentration. In summary, S12363 proved to be 18-83 times more active than the reference drugs in the MTT and 3-11 times more active than VDS in the clonogenic assay. Its high potency and dissimilar cell survival profile indicate that this compound possesses different biological properties, and therefore merits further in vivo evaluation. PMID- 8476209 TI - Role of N-linked glycosylation in cell-cycle progression and initiation of DNA synthesis in tumor-transformed human fibroblasts. AB - In this study we show that proliferation of cycling tumor-transformed human fibroblasts (line 90VAV1) is blocked specifically in G1 by HMG CoA reductase inhibition. This inhibition also resulted in a drastic depression of N-linked glycosylation, measured as incorporation of radioactive glucosamine into acid insoluble material. Following addition of mevalonate to cells arrested by HMG CoA reductase inhibitors, the depression of N-linked glycosylation was overcome and the cells initiated DNA synthesis. However, if the mevalonate-induced increase in protein glycosylation was prevented, due to addition of tunicamycin (an inhibitor of N-linked glycosylation), the cells were not able to proliferate. If instead tunicamycin was added 4 h after the addition of mevalonate, the cells synthesized DNA normally. Upon addition of tunicamycin, to cycling cells the progression through G1 was blocked in a similar way to that following HMG CoA reductase inhibition. Taken together, our data provide strong evidence for involvement of N linked glycosylation in the mevalonate-controlled cell cycle progression and growth activation of tumor-transformed human fibroblasts. PMID- 8476210 TI - Creation of ultra-rare restriction sites in intact eucaryotic chromosomes mediated by bacterial methylases: an approach to sequencing and analyzing tumor and normal genomes. AB - The limited restriction of eucaryotic chromosomes would facilitate our understanding of the aberrant genomes of genetic diseases and cancer. We have described methods for methylating eucaryotic chromosomes embedded in agarose plugs. We now describe how Cla I methylase can be utilized in a methylation dependent restriction cleavage with Dpn I to restrict eucaryotic genomes into a limited number of fragments. We have restricted the genomes of Saccharomyces cerevisiae at four sites and cleaved the three chromosomes of Schizosaccharomyces pombe into eleven fragments. Unlike the recently published methodologies using DNA sequences inserted into procaryotic and eucaryotic genomes, the methodologies described here use unaltered eucaryotic genomes for highly limited restriction. This methodology has applications in speeding, simplifying, and reducing the cost of sequencing the human genome. PMID- 8476211 TI - NK cells from mammary tumor bearing mice do not exert natural killer activity but function as antibody dependent cellular cytotoxicity effectors. AB - We have previously found that natural killer (NK) activity is profoundly decreased in BALB/c mice bearing large mammary tumors. Kinetic studies showed that after 14 days of tumor implantation a reduction of 25-40% of NK cytotoxicity can be observed and by 21 days only very low levels of NK reactivity can be detected in the spleens of tumor bearers. Phenotypic analyses of the splenic NK cells of tumor bearing mice revealed that they have similar density, granularity and comparable levels of NK 2.1 antigen on their surfaces as compared to NK cells from normal mice. However, in tumor bearers there was a shift from a high surface asialo GM1-bearing NK population to low-density surface asialo GM1-positive bearing cells. Phenotypically characterized NK cells were quantitated to test the possibility that splenic NK cells from tumor bearers migrated to other organs and were therefore at lower levels in the spleen. No significant differences were observed in the percentages of NK cells from spleens from normal and tumor bearing mice. Using single cell conjugate assays it was found that there was no impairment in the capacity of NK from tumor bearers to bind the NK-sensitive Yac 1 cells, however, this event did not result in lysis of the target cells. To elucidate whether the lytic machinery of the tumor bearers' NK cells was inactivated, their capacity to effect antibody dependent cellular cytotoxicity (ADCC) was evaluated. In contrast to the results observed when NK activity was evaluated, NK cells from tumor bearing mice exerted higher levels of ADCC than their normal counterparts and they had a higher expression of Fc receptors on their surfaces. These results suggest that the depression of NK activity observed in tumor bearing mice occurs at a triggering step that is not necessary for the activation of the NK effectors via the Fc receptor and that no major impairment of the lytic machinery occurs during mammary tumorigenesis. PMID- 8476212 TI - Disillusionments and hopes in the field of biological response modifiers. AB - A number of new approaches are currently being investigated throughout the world which aim at the better simulation of immunoregulation by different BRM's. However it must be accepted that a remarkable difference exists between the positive results obtained with BRM's in experimental tumor systems and current clinical experiences. It is suggested that the treatment of preneoplastic lesions and immunoprevention of cancer could be a more rational aim for the application of BRM's than the treatment of advanced neoplastic diseases. This hypothesis is based primarily on the theoretical understanding of the immune system as a biological mechanism whose "natural" function is to eliminate "minimal deviation" cells when they occur as regular biological events during cell multiplication. BRM's should be considered first of all as bioregulators for the maintenance and restoration of cellular and tissue homeostasis. PMID- 8476213 TI - Influence of preoperative performance status on survival time of patients with advanced gastric cancer following noncurative resection. AB - The relationship between preoperative performance status (PS) and the survival time of 152 patients with gastric cancer was determined following macroscopic noncurative resection and postoperative chemotherapy. There were no preoperative differences in laboratory data between the patients who led a normal life or those with a fully ambulatory performance status (PS 0 or 1) and those who were often bedridden (PS 2 or 3). Neither was there any difference between the groups with regard to clinicopathological factors. The doses of drugs prescribed were lower for patients with PS 2-3. There was no difference in the occurrence of drug toxicity between the groups. The patients with PS 0-1 had a significantly longer survival time than did those with PS 2-3 (P < 0.05). PS, a factor more easily measured than the stage of disease at the time of admission, correlates with survival time. We interpret our findings to mean that for patients with gastric cancer who are symptom-free or who are ambulatory with symptoms, clinical trials of drugs may prolong survival time. PMID- 8476214 TI - Relative activities of thymidylate synthetase and thymidine kinase in human mammary tumours. AB - Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High activities of TS and TK have been observed in rapidly proliferating tissues. In the present study, both enzyme activities were measured in 8 specimens of normal mammary tissues, 12 fibroadenomas and 10 adenocarcinomas in the human breast. The average activities of TS in fibroadenomas and adenocarcinomas were approximately 5- and 7-fold that in normal mammary tissues, respectively. The average activities of TK in fibroadenomas and adenocarcinomas were 4- and 14-fold that in normal mammary tissues, respectively. Thus, DNA synthesis in benign and malignant mammary tumors may be relatively predominant in de novo and salvage pathways, respectively. PMID- 8476215 TI - Effects of OK-432 on in vitro secondary responses of the non-adherent cells to IL 2 and OK-432 in cancer patients without tumor burden. AB - We examined the effect of OK-432 intracutaneous injection on the in vitro responses of non-adherent cells to IL-2 and OK-432, along with changes in lymphocyte subpopulations, in early cancer patients who underwent surgery. We found that 1) repeated injections of OK-432 resulted in an enhancement of LAK activity, the peak of which was seen between 7 and 10 days after the first administration, 2) this augmentation of LAK activity was not associated with changes in lymphocyte subpopulations CD8+ CD11- and CD8+ CD11+ phenotypes, and 3) the cytotoxic activity of lymphocytes stimulated in vitro with OK-432 did not show a definite change in specific pattern after in vitro OK-432 treatment. These findings indicate that repeated injections of OK-432 over a period of a week effectively enhanced LAK activity. PMID- 8476216 TI - Effects of thaliblastine on cytotoxicity and DNA damage in drug-sensitive and resistant rat ovarian tumor cells treated with cisplatin. AB - Combination effects of cisplatin (DDP) and thaliblastine (TBL) in DDP-sensitive (0-342) and -resistant (0-342/DDP) rat ovarian tumor cells were investigated. TBL alone, at either 40 or 80 micrograms/ml, exerted higher cytotoxicity in the DDP resistant 0-342/DDP cells than in the parental sensitive 0-342 cells in growth inhibition assay (% inhibitions: 12.5 and 42.8 in 0-342 cells vs. 37.5 and 66.1 in 0-342/DDP cells, at 40 and 80 micrograms/ml of TBL, respectively). TBL at 40 micrograms/ml showed an additive effect with DDP in the sensitive cells, while a synergistic cytotoxicity was observed in the resistant subline when the two drugs were used in combination, as exhibited by either % inhibition or cell viability. At 80 micrograms/ml of TBL, however, the combination effects were less than additive (infraadditive) in both lines, but still this treatment was more cytotoxic in 0-342/DDP cells. Alkaline elution assay showed that DDP induced higher DNA interstrand crosslings (ISCL) in 0-342 cells, while TBL produced DNA single strand breaks (SSB) in a dose-dependent manner in the resistant line but not in the sensitive cells. Combination of these two compounds resulted in a dramatic increase of DNA-SSB in 0-342/DDP cells. It is tentatively concluded that TBL might have some potential in combination with DDP to conquer the resistance in clinical use, which may result from its selective SSB-inducing activity in the resistant cells. PMID- 8476217 TI - Growth inhibitory substances in human breast cyst fluid. AB - Women who have breast cysts with intracystic Na/K < 3 may have a higher risk of breast cancer than those with intracystic Na/K > 3. Low/undetectable concentrations of TNF alpha and IL-4, both of which have been shown to inhibit growth of human breast cancer cell lines, were found in the majority of breast cyst fluid samples. Intracystic oestradiol concentrations were significantly higher in the low electrolyte ratio group than in the high electrolyte ratio group. Imbalance between growth stimulatory and growth inhibitory substances in cystic breast disease may be an explanation for the higher risk of breast cancer particularly in the low electrolyte ratio group. PMID- 8476218 TI - Heterogenic properties of clonal cell lines derived from canine mammary carcinomas and sensitivity to tamoxifen and doxorubicin. AB - Five clonal cell lines were established from each of 3 cell lines derived from 3 primary malignant canine mammary tumors. The clonal lines in each series were compared with one another and to the respective parent cell line with regard to cellular morphology, growth on plastic, cloning efficiency (CE) and colony sizes in soft agar, estrogen and progesterone receptor (ER, PR) status, and response to tamoxifen or doxorubicin in clonogenic assays. The most remarkable differences observed among the cell lines were in CE, colony sizes, and sensitivity to doxorubicin. The clonal line which contained measurable ER, had a shift in colony size distribution to smaller colonies when exposed to tamoxifen or tamoxifen with estradiol that may have been estrogen-receptor mediated. PMID- 8476219 TI - Influence of syngeneic (anti-idiotypic) antibody responses on biodistribution and tumour localisation of murine monoclonal antibodies and fragments. AB - Balb/c mice were immunised with three different syngeneic monoclonal antibodies (Mabs). Following injection of radiolabelled Mabs into mice with anti-antibody responses they were cleared from the circulation, predominantly to the liver, due to the formation of immune complexes. Anti-antibody titres as low as 1/100 were virtually as effective as 1/3,000 in perturbing biodistribution of Mabs. There were no effects against isotype matched control Mabs. There was a much lesser effect against Fab or F (ab')2 of one Mab, although these did form immune complexes in the circulation of immune mice. With Fab of another Mab its blood survival was actually prolonged, due to immune complex formation. With this Fab, although blood survival was prolonged, localisation into human tumour xenografts expressing its target antigen in Nude mice was reduced by pre-treatment with immune serum. These studies show that syngeneic (anti-idiotypic) responses have a detrimental effect on the pharmacokinetics of Mabs, but with more diverse effects on their fragments. With fragments the indication is that even when biodistribution is not grossly perturbed, tumour recognition may still be restricted. PMID- 8476220 TI - An analysis of vincristine-resistance in BHK cells pretreated with 1-beta-D arabinofuranosylcytosine. AB - As with SV40-transformed BHK cells (1), pretreatment of BHK cells with 1-beta-D arabinofuranosylcytosine (araC) very markedly enhanced the resistance frequency to N-phosphonoacetyl-L-aspartate (PALA) but only modestly increased the resistance frequency to vincristine (VCR). AraC pretreatment of cells that already had moderate VCR-resistance again only modestly enhanced the resistance frequency at a higher VCR concentration. By contrast, delaying the addition of VCR to BHK cells by 7-24 hours after pretreatment with araC increased the enhancement of VCR-resistance frequency to a level comparable to the enhancement of PALA-resistance frequency. VCR-resistant clones isolated without or after araC pretreatment were analysed for amplification of the multidrug resistance (mdr) gene. One of four clones isolated by single-step selection with no araC pretreatment and four of six clones isolated after araC pretreatment showed amplification of the mdr gene. All VCR-resistant clones tested were cross resistant to actinomycin D and VCR-resistance was inhibited by treatment with verapamil. PMID- 8476221 TI - Human lung and bladder carcinoma tumors as compared to their adjacent normal tissue have elevated AP-1 activity associated with the retinoblastoma gene promoter. AB - Examination of the nucleotide sequence of the retinoblastoma (Rb) promoter revealed the presence of a DNA region highly homologous to the recognition site for the cellular transcription factor AP-1. A pair of complementary oligonucleotides containing the AP-1 site was synthesized and used in gel retardation assays to determine the role of the AP-1 protein in the regulation of the Rb gene expression. Using nuclear extracts from Hela cells as well as from lung and bladder tumors, we found specific binding of the AP-1 protein to this oligonucleotide. This binding is elevated in Hela cells, in 10/13 lung and 3/8 bladder tumors as compared to adjacent normal tissue. These results suggest that AP-1 could be implicated in Rb gene transcriptional regulation through its interaction with the AP-1 binding site of the Rb gene promoter. PMID- 8476222 TI - Antiplasmid and carcinogenic molecular orbitals of benz[c]acridine and related compounds. AB - Effect of K- and L- molecular orbital regions on expression of antiplasmid and carcinogenic activity was studied with various benz[c]acridine derivatives, tricyclic compounds (acridine orange, phenothiazines) and dibenzoazepine (imipramine). Antiplasmid compounds showed the out-of-phase of molecular orbital in the L-region. On the other hand, mutagenic and carcinogenic compounds showed the out-of-phase in the L-region, and their energy was accumulated in the K region of the molecular orbitals. The present study suggests that the molecular orbitals responsible for the expression of antiplasmid and carcinogenic effects might be basically different. PMID- 8476223 TI - Postgastrectomy anticancer chemotherapy for stage IV gastric cancer equally tolerable for patients under and over age 65. AB - We compared the survival time and drug toxicity between patients with stage IV gastric cancer who were over and under 65 years. All had undergone gastric resection followed by treatment with mitomycin C and a fluorinated pyrimidine. There were no differences in prognostic factors or doses of drugs prescribed between the two groups, nor were there differences in survival rates or toxicities. As advanced chronological age is not sufficient justification to limit or withhold treatment with anticancer drugs, postoperative chemotherapy should be designed for patients with gastric cancer, regardless of age. PMID- 8476224 TI - 5'-Nor-anhydrovinblastine (Navelbine) has an anti-invasive effect on MO4 mouse fibrosarcoma cells in vitro and in vivo. AB - 5'-nor-anhydrovinblastine (Navelbine) is a hemisynthetic Vinca alkaloid for which a selectivity for mitotic microtubules has been demonstrated. In previous studies, we have demonstrated an anti-invasive effect of other Vinca alkaloids. Here the results of in vitro and in vivo assays concerning the effect of 5'-nor anhydrovinblastine on growth and invasion of MO4 cells are presented. It is demonstrated that at cytostatic concentrations, 5'-nor-anhydrovinblastine also has an anti-invasive effect. PMID- 8476225 TI - Modulation of biological responses of normal human mononuclear cells by antiestrogens. AB - The effect of three non-steroidal antiestrogens, Tamoxifen, Toremifene and ICI 164, 384, on various aspects of the immune response was studied in cultures of normal peripheral mononuclear blood cells. The drugs differ somewhat in their effect on the functions tested (pokeweed mitogen-induced immunoglobulin synthesis and cell proliferation, mixed lymphocyte reaction, Interleukin 2 (IL 2) synthesis, IL 2 receptor expression and Tumor Necrosis Factor (TNF alpha) synthesis). However, all three are immunosuppressive. On the other hand, ICI 164, 384 and Tamoxifen were stimulatory for TNF alpha production by adherent cells which may prove as an additional feature in antiestrogen treatment. PMID- 8476226 TI - Evaluation of S12363, a novel vinca alkaloid drug in the treatment of advanced malignant melanoma. A phase II study. AB - We conducted a phase II study with the new vinca alkaloid derivative S12363 in ten patients with metastatic malignant melanoma. Six patients had been pre treated with other cytotoxic agents and all had received Vindesine. Four patients had no prior systemic treatment before entry into the study. S12363 was well tolerated subjectively, the main toxicity being haematological. Despite encouraging in vitro observations, no objective responses to S12363 have been documented in these patients with the doses and schedule used in this study. S12363 appears to have no clinically useful activity in metastatic malignant melanoma. PMID- 8476227 TI - Chemoprevention by indomethacin of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder tumors. AB - The effects of indomethacin on the development of N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBn)-induced urinary bladder tumors were evaluated in male BDF mice. Preliminary feeding studies revealed that the highest non-toxic dose of indomethacin was 15 mg/kg of AIN-76A diet; thus, dose levels of 15 and 7.5 mg/kg of diet were selected to determine the chemopreventive efficacy of this agent. Diet supplementation with indomethacin was initiated when the mice were 49 days old and continued for the duration of the study. Starting one week after indomethacin treatment, OH-BBN was administered 1x/week for eight weeks. Upon termination of the study (180 days after the initial carcinogen administration), all tumors in the urinary bladder were removed and classified histologically. Mice receiving carcinogen and no indomethacin supplementation had a 24% incidence of urinary bladder tumors; mice receiving 7.5 mg/kg and 15 mg of indomethacin had a 5% and 0% incidence of urinary bladder tumors, respectively. The significant reduction of OH-BBN-induced urinary bladder tumors by indomethacin is consistent with previous suggestions that prostaglandin synthesis inhibitors are effective inhibitors of carcinogenesis. PMID- 8476228 TI - Antitumor activity and interleukin-1 induction by tannins. AB - The relationships between structures, antitumor activities and interleukin-1 (IL 1) induction by fifteen tannins were studies. When tannins (10 mg/kg) were intraperitoneally injected into mice once, 4 days before intraperitoneal inoculation of S-180 cells, tellimagrandin II, rugosin A, hirtellin B, oenothein B and oenothein A, which have only tellimagrandins I or II units in their molecules, had significant antitumor activity. Although casuarictin and its related tannins were ineffective, agrimonin, which is a dimer, had a strong effect, as previously reported. On the other hand, monomeric ellagitannins such as tellimagrandins I and II, rugosin A and casuarictin also increased IL-1 beta production from human peripheral macrophages in vitro by 2-fold over the non stimulated basal production and oligomeric ellagitannins with strong antitumor activity more potently stimulated the IL-1 beta induction. Other tannins having no antitumor activity induced less IL-beta. This study indicates that oligomeric ellagitannins, which consist of tellimagrandin I or II, casuarictin or their related structure units, have antitumor activity and induce IL-1 beta. PMID- 8476229 TI - Cytotoxic activity of fusaric acid on human adenocarcinoma cells in tissue culture. AB - When cultured human normal WI-38 fibroblasts were exposed to 500 microM fusaric acid (5-butylpicolinic acid), cell proliferation ceases. The majority of the WI 38 cells remained in a quiescent G1(G0) state and viable for approximately 30 to 48 h. The effect of fusaric acid on WI-38 cell growth was slowly reversible after removal of the agent from the culture media. In contrast, within 24 h of exposure to 500 microM fusaric acid, most of the human colon adenocarcinoma LoVo cells were blocked at random in the cell cycle and approximately 80% of the cells were dead after 30 h. Three additional human colorectal adenocarcinoma cell lines, denoted SW48, SW480, and SW742, were also sensitive to the inhibitory and cytotoxic effects of fusaric acid. Of all the cell lines tested, the human mammary adenocarcinoma cell line MDA-MB-468 was the most sensitive to the growth inhibitory and cytotoxic effects of fusaric acid. Further experiments with MDA-MB 468 cells demonstrated that fusaric acid is a potent inhibitor of DNA synthesis. Fusaric acid also inhibited the growth of human epidermoid carcinoma KB cells and showed cytotoxic actions for this cell line but its effects on cell viability were not as pronounced. The results presented here indicate that fusaric acid has potent anti-proliferative activity in vitro on various normal and cancer cell lines and suggest that it exhibits some cytotoxic specificity for growing and confluent colorectal adenocarcinoma and mammary adenocarcinoma cell lines. PMID- 8476230 TI - Pharmacokinetic studies of chloroethylnitrosocarbamoyl-amino acid derivatives in vivo and in vitro. AB - The in vitro chemosensitivity of MAC 15A ascites cells to CNC-alanylalanine and CNC-glycinemethylamide was assessed using a clonogenic assay system. In vitro stability studies and in vivo pharmacokinetics were performed using a reversed phase HPLC technique. Initial concentrations of CNC-alanylalanine and CNC glycinemethylamide of 5.2 micrograms ml-1 and 3.2 micrograms ml-1 respectively, were required for a 70% reduction in colony formation of MAC 15A cells in vitro. The concentrations of active alkylating species generated were calculated from the drug half-lives in tissue culture medium. On this basis, a 70% cell kill was achieved by equivalent concentrations of 10.8 microM CNC-alanylalanine and 10.6 microM CNC-glycinemethylamide. Analysis of drug levels following intraperitoneal administration revealed that CNC-alanylalanine was cleared more slowly from the peritoneal cavity producing a greater drug concentration at the site of the ascitic MAC 15A tumour. These results suggested that the superior activity of CNC alanylalanine over CNC-glycinemethylamide against MAC 15A in vivo could be attributed mainly to differences in the pharmacokinetic behaviour of the two drugs following intraperitoneal administration and that CNC-alanylalanine might have a role in the treatment of local peritoneal disease. PMID- 8476231 TI - Influence of acetylsalicylic acid on antibody-dependent cellular cytotoxicity (ADCC) of peritoneal macrophages. AB - Very recent evidence indicates that, in addition to its already known analgesic, anti-inflammatory, antipyretic, and platelet-aggregation-inhibiting properties, acetylsalicylic acid (ASA) exerts a positive influence on the immune system. Therefore, its action on murine peritoneal macrophages was investigated in the present study. Various ASA concentrations (50-200 micrograms/ml) failed to have any stimulating or inhibiting effect on antibody-dependent cellular cytotoxicity (ADCC) and on the binding capacity of macrophages from various levels of activation against SW 707 tumor cells. Furthermore, no time dependence of the stimulation was observed over a period of up to 48 hrs. These results suggest that the reported positive effect of ASA on the immune system, manifested by increased production of interleukins and interferon, is due to an interaction of macrophages and lymphocytes and not to a direct increase in macrophage activity. PMID- 8476232 TI - Interactions between oestradiol and danazol on the growth of gastrointestinal tumour cells. AB - The gastrointestinal tumour cell lines, MKN45G and C146 possessed oestrogen receptors (ER) of affinities 1.8 x 10(-8) and 5.2 x 10(-9) M respectively. C146 and MKN45G had enhanced proliferation in the presence of oestradiol (10(-8) and 10(-10) M). Fifty-six percent (5/9) of primary gastric and colorectal tumours had their proliferation enhanced by oestradiol. The anti-steroidal drug, danazol, inhibited the basal growth of MKN45G (10 micrograms ml-1 45% of the untreated control), C146 (10 and 5 micrograms ml-1, 20 and 48% of control, respectively) and 3/9 GI primary tumours (10 micrograms ml-1). Danazol competed with 3 [H] Oestradiol for binding to ER on MKN45G and C146, at concentrations from 10 to 1 micrograms ml-1. PMID- 8476233 TI - Antibiotic therapy for chronic infection of pseudomonas in the lung. AB - Chronic Pseudomonas aeruginosa lung infection is an endobronchiolitis characterized by the microcolony mode of growth (biofilm). Early colonization is treated with oral ciprofloxacin combined with colistin inhalation. Chronic infection is treated with "maintenance chemotherapy" consisting of beta-lactam antibiotics and tobramycin intravenously in combination with colistin inhalation four times yearly. PMID- 8476234 TI - Pathogenesis and pathophysiology of bacterial meningitis. AB - Despite the availability of bactericidal antibiotics with potent in vitro activity against the major meningeal pathogens, the morbidity and mortality from bacterial meningitis remains unacceptably high. Animal models have proven to be extremely valuable in the study of the pathogenesis and pathophysiology of bacterial meningitis, with the hopes of providing new information that may lead to an improved outcome from this disorder. Bacterial meningitis usually begins with nasopharyngeal colonization by a new organism, followed by invasion and bacteremia. Subsequently there is central nervous system invasion, although the exact site and mechanism of meningeal invasion are unknown. The generation of an intense subarachnoid space inflammatory response, induced by release of bacterial virulence factors and/or inflammatory cytokines, contributes to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema, increased intracranial pressure, and alterations of cerebral blood flow. Attenuation of this inflammatory response (e.g. by co-administration of antiinflammatory agents) may diminish many of these pathophysiologic consequences of meningitis, and perhaps improve morbidity and mortality from this disorder. PMID- 8476235 TI - Role of bacterial cytotoxins in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. AB - Bacterial cytotoxins, which are produced by Shigella dysenteriae 1 and certain E. coli serotypes, kill mammalian cells by inhibiting protein synthesis. They have been related to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, probably by initial insult to vascular endothelial cells. This insight opened new avenues of research and possible interventions. PMID- 8476236 TI - Role of insulin resistance in human disease (syndrome X): an expanded definition. AB - Resistance to insulin-mediated glucose uptake is characteristic of individuals with impaired glucose intolerance or non-insulin-dependent diabetes, and it also occurs commonly in patients with high blood pressure. The physiological response to a decrease in insulin-mediated glucose uptake is an increase in insulin secretion, and as long as a state of compensatory hyperinsulinemia can be maintained, frank decompensation of glucose tolerance can be prevented. However, it is likely that the defect in insulin action and/or the associated hyperinsulinemia will lead to an increase in plasma triglyceride and a decrease in high density lipoprotein-cholesterol concentration, and high blood pressure. It seems likely that the cluster of changes associated with resistance to insulin mediated glucose uptake comprise a syndrome, which plays an important role in the etiology and clinical course of patients with non-insulin-dependent diabetes, high blood pressure, and coronary heart disease. PMID- 8476237 TI - Nonatheromatous arterial thrombosis. AB - In contrast to venous thrombi, which are caused primarily by reduced blood flow and are composed predominantly of fibrin and red cells, arterial thrombi characteristically result from elevated shear stress at sites of vascular injury and are composed predominantly of platelets. Arterial thrombosis is therefore typically caused by abnormalities of platelets and/or the vessel wall. Disorders characterized by a propensity to arterial thrombosis due primarily to abnormalities of platelets include the myeloproliferative disorders, those due to vessel wall abnormalities include homocystinuria and the inflammatory vasculopathies, while those probably due to a combination of platelet and vessel wall abnormalities include heparin-associated thrombocytopenia and thrombosis and the antiphospholipid antibody syndrome. PMID- 8476238 TI - Physiologic role of the normal pericardium. AB - Because of the characteristics of the parietal pericardial tissue, the intact pericardial sac has a limited reserve volume, becoming relatively non-compliant when the heart volume is at the high end of the normal physiologic range. Pericardial restraint of the heart is best considered as a contact force. Measured with flattened balloons, the magnitude of pericardial contact pressure is probably several mmHg less than right atrial pressure. The diastolic pressure volume relationship of the right ventricle, and to a lesser degree of the left ventricle, shifts downward following pericardiectomy. In dogs, the pericardium has been shown to limit maximal cardiac output. Some disease states associated with a rapid increase in total heart volume, including subacute mitral regurgitation and right ventricular infarction, demonstrate an increased pericardial influence on cardiac filling. PMID- 8476239 TI - Primary repair and autotransplantation of cardiac valves. AB - The aortic valve is a beautifully designed and balanced structure with precise opening and closing mechanisms. Its design probably cannot be improved upon by man-made mechanical devices, no matter how ingenious. It is logical to use human valves as replacements because of their superior structural configuration. Their chief difficulties are in the troubles of the learning curve of the surgeon to achieve a competent mechanism and the hazard of infection. The pulmonary autograft or translocation of the pulmonary valve to the aortic position offers many advantages, and the long-term results are good. Conservative repair and reconstruction of the aortic valve are increasing in popularity but have a relatively limited application. The mitral valve has a less precise and more adjustable type of mechanism and generous leaflet coaptation. These features make it more amenable to repair, as demonstrated in the clinical series of the technique. Repair is clearly preferable to replacement at present. The tricuspid valve is eminently suitable for reconstruction, but late results are not very good. The disappointing outcome, however, reflects more the severity of underlying cardiac pathology than the effectiveness of the repair. PMID- 8476240 TI - Epidermolysis bullosa. AB - Epidermolysis bullosa is a group of genetically determined diseases characterized by abnormal fragility of the skin and mucosa. In this chapter, we review current thinking about classification, pathogenesis, and molecular genetics, and we discuss management guidelines. PMID- 8476241 TI - Management of primary hyperparathyroidism. AB - Primary hyperparathyroidism is a common disease that can be accurately diagnosed and effectively treated in most patients. The diagnosis is established by a persistent elevation of serum calcium and parathyroid hormone and by clinical evaluation. Surgery is the appropriate treatment, and preoperative localization procedures are seldom indicated. Selected patients with mild disease may be followed by procedures devised to identify deterioration of skeletal, neurological, and renal function. The accurate diagnosis and effective treatment of primary hyperparathyroidism are rewarding clinical experiences for the endocrinologist and surgeon. PMID- 8476242 TI - Prognostic factors and therapeutic decisions in axillary node-negative breast cancer. AB - The incidence of node-negative breast cancer is increasing, and it is becoming a more commonly encountered clinical problem. Prognostic factors such as tumor size, histopathological characteristics, receptor status, proliferative markers, biochemical alterations, and gene abnormalities can be useful in assessing the risk of cancer recurrence after primary local therapy. By accurately assessing the risk of recurrence, informed decisions can be made about whether or not to treat with adjuvant systemic therapy. PMID- 8476243 TI - Chronic inflammatory demyelinating polyradiculoneuropathy. AB - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represents an important acquired condition characterized by progressive, symmetrical, proximal and distal weakness. Muscle stretch reflexes are depressed and sensory loss is variable. Patients may have mild to severe weakness and may require assisted ambulation or wheelchairs. Rarely do patients require respiratory support. Laboratory features include nerve conduction changes and nerve biopsy pathology indicative of demyelination. Cerebrospinal fluid protein is characteristically elevated without pleocytosis. The condition is responsive to immunosuppressive therapy, especially prednisone and plasmapheresis (plasma exchange). CIDP frequently follows a chronic or relapsing course. PMID- 8476244 TI - Primary sclerosing cholangitis. AB - Primary sclerosing cholangitis (PSC) is an inflammatory disease of unknown etiology. It affects the biliary system and is characterized by fibrosis and progressive obliteration of extrahepatic and intrahepatic bile ducts. Its frequent coexistence with antibody-mediated diseases, certain human leukocyte antigens, and altered lymphocyte mechanisms suggests a strong autoimmune and genetic etiology. Other conditions such as recurrent cholangitis, acquired immunodeficiency syndrome, previous bile duct surgery, bile duct anomalies, or biliary stone disease may result in similar clinical patterns and radiologic profiles. PSC can be asymptomatic and slowly progressive over years, or it may develop rapidly with an inexorable progression to cirrhosis and portal hypertension. Clinical and biochemical abnormalities may suggest PSC, but it is the characteristic radiological pattern that secures the diagnosis. Once viewed as a rare entity, the widespread use of radiological and endoscopic methods have increased physician awareness. There is no successful medical treatment for PSC. While traditional surgical approaches have been directed at the relief of cholangitis and biliary obstruction, liver transplantation has emerged as definitive therapy for patients with PSC complicated by cirrhosis or recurrent bouts of cholangitis. PMID- 8476245 TI - Anti-inflammatory therapy for asthma. AB - Asthma is now recognized to be a chronic inflammatory disease of the airways, involving mast cells, eosinophils, and T lymphocytes. Treatment of asthma should therefore be based on anti-inflammatory agents rather than bronchodilators. Choices include inhaled corticosteroids, which are highly effective in all patients, and cromolyn sodium and nedocromil sodium, which are effective in patients with mild asthma. It is likely that the earlier and more widespread use of anti-inflammatory drugs will reduce the unacceptably high morbidity and mortality of asthma and prevent irreversible chronic airflow obstruction in patients with severe disease. PMID- 8476246 TI - Recombinant erythropoietin. AB - Erythropoietin is the only hematopoietic growth factor that behaves like a hormone. Produced in the kidneys and the liver, erythropoietin interacts with erythroid progenitor cells in the bone marrow to promote their proliferation and maintain their viability. Erythropoietin production is regulated at the level of its gene by tissue oxygenation; hypoxia or anemia stimulates erythropoietin production, and erythrocytosis suppresses it, but never completely. The plasma erythropoietin concentration reflects erythropoietin production and can be used to define erythropoietin-deficient states in which anemia may be amenable to correction by administration of recombinant human erythropoietin. PMID- 8476247 TI - Bone marrow transplantation for Hodgkin's disease and lymphoma. AB - The treatment of patients with high-dose chemotherapy and autologous transplantation for recurrent or high-risk lymphomas has greatly expanded over the past few years. With the use of new supportive care measures such as newer antibiotics and hematopoietic growth factors, the morbidity and mortality rate associated with this therapy have diminished. This in turn has allowed successful use of the therapy earlier in the disease course, with resultant increases in disease-free survival rates. Future trials will strive to utilize new therapies and supportive care measures to improve on the results even further. PMID- 8476248 TI - Diagnosis and treatment of osteoporosis. AB - Osteoporotic bone fractures are a significant public health problem resulting in substantial morbidity and for those who suffer a hip fracture, a significant one year mortality. Bone densitometry provides an important measure of fracture risk and the newer techniques are useful in the management of individuals with osteoporosis. Estrogen administration will preserve bone mass in postmenopausal women, and the optimal intake of calcium and vitamin D is being evaluated. Newer agents such as calcitonin and bisphosphonates may provide potent therapies for preventing bone loss. This review focuses on bone densitometry as a diagnostic tool and on the use of therapeutic agents for osteoporosis. PMID- 8476249 TI - Cellular mechanisms of acute ischemic injury in the kidney. AB - Hypoxic injury to tubular cells represents an early event in acute renal failure. Although important advances have been made in the understanding of hypoxic injury at the cellular level (e.g. loss of cell polarity, production of free radicals, calcium entry, and the activation of genes for protection or regeneration), the basic mechanisms responsible for organ failure remain elusive. The renal medulla, working on the brink of anoxia and being the site of concentration for many toxins, may be an important target for the synergistic events of hypoperfusion and nephrotoxic exposure that often precede human acute renal failure. PMID- 8476250 TI - Neuromodulation techniques for medically refractory chronic pain. AB - Advances in our knowledge of the physiology of pain transmission and modulation have created new surgical options for the control of chronic pain. The pain modulation network can be activated by administration of spinal opiates or by electrical stimulation of the nervous system with transcutaneous, peripheral nerve, spinal cord, and deep brain stimulation. The theoretical basis and the clinical applications of neurostimulation for the treatment of medically intractable chronic pain are reviewed. PMID- 8476251 TI - Control of brain volume during hyperosmolar and hypoosmolar conditions. AB - The brain is particularly vulnerable to disturbances of body fluid osmolality. Studies in animals indicate that brain adaptation to osmotic stresses is a very complex process involving transient changes in water content and sustained changes in electrolyte and organic osmolyte contents. Appreciation of the nature of the adaptation process enables a better understanding of the marked variations in neurological sequelae that characterize hyper- and hypoosmolar states and provides a basis for more rational therapy. PMID- 8476252 TI - Diabetic nephropathy: pathogenesis and treatment. AB - Diabetic nephropathy is a leading cause of end-stage renal disease. Recently, there have been developments in understanding the role of risk factors and pathogenetic features such as genetic predisposition, systemic and intraglomerular hypertension, the effects of glycemic control, glomerular hypertrophy, and basic biochemical alterations in cellular metabolism, as well as correlations in morphology and function. These are reflected in newer approaches to preventive and palliative therapy. PMID- 8476253 TI - Laparoscopic therapy of cholelithiasis. AB - Laparoscopic cholecystectomy has emerged as the treatment of choice for symptomatic cholecystolithiasis. Results will improve and complications rates decrease as surgeons gain experience in the method. New developments will permit a complete laparoscopic approach to cholelithiasis. PMID- 8476254 TI - Malignant melanoma. AB - Malignant melanoma is the most rapidly increasing cancer in Caucasians throughout the world. The increased incidence is due to greater sun exposure arising from changes in clothing habits and life-styles over the past fifty years. Most melanomas arise in preexisting moles in sun-exposed sites and may spread rapidly via the vascular system if not detected and removed early. Treatment of disseminated disease is unsatisfactory, with most patients dying of refractory brain metastases. PMID- 8476255 TI - Interleukin-2 receptor-directed therapies: antibody-or cytokine-based targeting molecules. AB - With the exception of certain hematologic malignancies, the high affinity interleukin-2 (IL-2) receptor is only transiently expressed during the brief antigen-triggered proliferative burst of lymphocytes. Hence, we wondered whether administration of anti-IL-2 receptor (IL-2R) monoclonal antibody (mAb) or chimeric IL-2 toxins would provide a utilitarian way to achieve immunosuppression aimed directly at activated lymphocytes, or whether this approach could be used to treat IL-2R+ leukemia/lymphoma. Studies in preclinical autoimmune and transplant models indicate that this approach can be effective. The results of open, uncontrolled studies provide preliminary evidence that a chimeric IL-2 toxin is well tolerated at doses that may induce improvement in patients with IL 2R+ leukemia/lymphoma, as well as in patients with refractory rheumatoid arthritis or new-onset diabetes mellitus. PMID- 8476256 TI - Special aspects of neuropsychiatric illness in women: with a focus on depression. AB - Many depressive disorders predominate in women. Other psychiatric disorders more prevalent in women than men often occur concomitantly with depression. A variety of these disorders show a premenstrual patterning of symptoms and are responsive to antidepressants. Migraine headaches are also more common in women, show a premenstrual patterning, and are responsive to antidepressants. Other neuropsychiatric and endocrine-related disorders predominating in women are discussed in this review. Greater attention to the special aspects of neuropsychiatric disorders in women may improve diagnosis and treatment. PMID- 8476257 TI - Atherosclerosis regression, plaque disruption, and cardiovascular events: a rationale for lipid lowering in coronary artery disease. AB - In the Familial Atherosclerosis Treatment Study (FATS), the reduction in clinical events (75%) far outweighed the modest frequency and magnitude of lesion regression observed among those receiving intensive lipid-lowering therapy. To understand this result, the disruptive changes in plaque that trigger clinical events (cardiac death, myocardial infarction, unstable angina) are described. Data are presented in support of the idea that the clinical benefits of lipid lowering therapy are best explained by stabilization, by depletion of lipid, of the "dangerous" subpopulation of lipid-rich plaques that are often associated with only mild or moderate coronary narrowing. PMID- 8476258 TI - Prophylactic antibiotics in surgery. AB - Prophylactic antibiotics can decrease the incidence of postoperative wound infections in indicated procedures. The accepted indications for administering prophylactic antibiotics have been clean-contaminated procedures and prosthesis insertion, but new indications are evolving that consider wound contamination together with anesthetic risk and relative duration of the operation. A prophylactic antibiotic is chosen on the basis of its activity against endogenous flora likely to be encountered, its toxicity, and its cost, in that order. Potent antibiotics used for serious infections are generally not used for prophylaxis. A maximum dose of a prophylactic antibiotic is given preoperatively so that effective tissue concentration is present at and after the time of incision. In the absence of infection, antibiotics should not be continued beyond the operative day. Regimens for specific procedures are discussed. PMID- 8476259 TI - The diagnosis and treatment of panic disorder. AB - Panic attacks and panic disorder often first present in the emergency room or to the family practitioner. The presentation and differential diagnosis of this disabling disorder are described in this review, together with the etiology and health effects of the syndrome. Both medication and psychological treatments are described, as are the indications, side effects, and expected outcome for each therapy alone and in combination. PMID- 8476260 TI - Endothelial dysfunction in coronary artery disease. AB - The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle cells. Monoaminooxidase deactivates catecholamines and serotonin. Angiotensin converting enzyme transforms angiotensin I into angiotensin II and breaks down bradykinin into inactive products. Nitric oxide is a potent vasodilator and inhibitor of platelet function that under most circumstances is released together with prostacyclin, which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin 1, thromboxane A2, and endoperoxides. Endothelium-derived growth inhibitors include heparin (sulfates) and transforming growth factor beta 1, while basic fibroblast growth factors and platelet-derived growth factor and possibly endothelin promote proliferation. Because of its strategic anatomic position, the endothelium is a primary target for injuries and cardiovascular risk factors. In particular, aging, low density lipoproteins, hypertension, diabetes, and ischemia alter endothelium function. In arterial coronary bypass grafts, the release of nitric oxide is more pronounced than in vein grafts. Alterations of endothelial function may contribute to vasospasm, thrombus formation, and vascular proliferation and in turn myocardial ischemia, all common events in patients with coronary artery disease. PMID- 8476261 TI - Aging--causes and defenses. AB - Recent studies have shown that chromosomes shorten as cells divide and become senescent. Also, deletions in mitochondrial DNA increase markedly with advancing age, presumably secondary to damage from oxygen radicals. Since host defenses against environmental factors also become attenuated, the molecular damage associated with aging may increasingly perturb normal homeostasis and increase the susceptibility to disease and disability. Such age-associated dysfunctions can be targeted and interrupted. PMID- 8476262 TI - Current approaches in the treatment of Parkinson's disease. AB - Treatment options for patients with Parkinson's disease have rapidly expanded in the last five years. They now include pharmacologic therapies designed not only to improve parkinsonian symptoms, but also to prevent disease progression. In addition, neurosurgical options and other novel treatment strategies are being developed and may become clinically useful in the next decade. This chapter addresses current and evolving Parkinson's disease medications, future surgical interventions, and specific strategies for maximizing patient motor abilities. PMID- 8476263 TI - Idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis kills half of its victims within five years of diagnosis. Currently available treatment regimens are disappointing, and the incidence of the disease appears to be increasing. Newer techniques of imaging coupled with laboratory advances in molecular and cellular biology may produce new strategies for modulating the disease process. This article explores new approaches to the diagnosis and management of idiopathic pulmonary fibrosis. PMID- 8476264 TI - Antioncogenes and human cancer. AB - Multiple genetic lesions are thought to transform a normal cell into a malignant one, and both dominant and recessive genetic effects have been identified in this process. Antioncogenes (or tumor suppressor genes) act in a recessive manner, in which both maternal and paternal alleles need to be inactivated to abrogate normal function. The identification of these lesions is giving us insight into the regulatory pathways in the cell and may translate into future improvements in prevention, diagnosis, prognosis, and therapy of human cancer. PMID- 8476265 TI - Angioplasty for acute coronary syndromes. AB - The acute ischemic syndromes (unstable angina and acute myocardial infarction) are often treated with percutaneous transluminal coronary angioplasty. Angioplasty should be considered in patients with unstable angina refractory to medical therapy and in those with evidence for ischemia after medical stabilization. Direct or primary angioplasty is indicated in patients with acute myocardial infarction with contraindications to thrombolytic therapy and is a reasonable alternative even in those eligible for thrombolytics. While there is no role for immediate angioplasty of a patent infarct-related artery following thrombolysis, rescue angioplasty of persistently occluded arteries may be beneficial, although further studies are needed. PMID- 8476267 TI - Diagnosis and treatment of obsessive compulsive disorder. AB - Obsessive compulsive disorder (OCD) is a common anxiety disorder that appears to be due to a disturbance in central serotonergic functioning. Drugs, such as clomipramine, that inhibit neuronal reuptake of serotonin are effective in treating OCD. Behavioral therapy techniques are also effective. PMID- 8476266 TI - Methods, successes, and failures of smoking cessation programs. AB - Addictive and conditioning processes interact to make cigarette smoking a common, lethal behavior that is highly resistant to change. In addition to addiction and conditioning, smoking is maintained by a wide range of forces, ranging from social modeling and advertising to the politics and economics of international trade. Parallel to this wide range of causes of smoking, interventions to encourage smoking cessation range from simple information and suggestions to smoking cessation classes, to nicotine replacement, to community or national campaigns that promote nonsmoking. Clinicians can make contributions throughout this range of activities, from the consulting room to political advocacy. While no one of these is highly successful on its own, together they have prompted almost 50% of smokers to quit, an impressive accomplishment. PMID- 8476268 TI - Serum transferrin receptor. AB - The transferrin receptor plays a critical role in iron metabolism by precisely controlling the flow of transferrin iron into body cells. A soluble truncated form of the receptor can be detected in human serum using sensitive immunoassays, and the initial clinical experience with this new measurement indicates that it reflects the total body mass of tissue receptor. Serum receptor levels rise significantly with tissue iron deficiency and the heightened demand for iron associated with expansion of the erythroid marrow. The serum receptor provides a quantitative measure of functional iron deficiency and distinguishes the associated anemia from that of chronic disease. If iron deficiency is excluded, the serum receptor provides a quantitative measure of total erythropoiesis that is more sensitive and less invasive than bone marrow examination currently used to assess red cell precursor mass. Performed in conjunction with serum ferritin measurements, the serum receptor will be useful in establishing the true prevalence of iron deficiency anemia in population studies. PMID- 8476269 TI - Utility of gene rearrangements in lymphoid malignancies. AB - Molecular genetic study of lymphoid neoplasms by Southern blotting or polymerase chain reaction permits the ready detection of gene rearrangements. Clonal rearrangements of immunoglobulin and T-cell receptor genes identify neoplasms of B- and T-cell lineage, respectively. Additionally, lymphoma-specific chromosome translocations involving oncogenes are detected with the same molecular techniques. Probes are currently available to study the c-myc translocations of Burkitt's lymphoma, the bcl-2 translocations of follicular lymphomas, and the bcl 1 translocations of centrocytic lymphoma. PMID- 8476270 TI - The biology of the eosinophilic leukocyte. AB - The eosinophil is characterized by specific cytoplasmic granules that contain a series of cationic toxins able to kill many targets, including helminths, protozoa, bacteria, and other cells. In bronchial asthma, considerable evidence exists that the eosinophil releases granule proteins, especially the major basic protein (MBP), which in turn mediate tissue abnormalities. Among eosinophil activating factors, IL-5 has been associated with helminth infection and hypersensitivity diseases and would appear to be an attractive target for pharmacological intervention. PMID- 8476271 TI - Scaphocephaly in a prehistoric skeleton from Harappa, Pakistan. AB - Irregularities of cranial suture closure resulting in scaphocephaly are documented for a number of prehistoric and historic human populations of the eastern and western hemispheres, but what may be the first recorded case from southern Asia appeared during the 1987 archaeological field season at the Indus Valley Civilization site of Harappa, Pakistan. The female specimen with this condition also exhibits indicators of developmental abnormalities in the postcranial skeleton. These features are discussed in the context of assessing anatomical and ontogenetical relationships of craniostenostic eccentricities with abnormalities of facial, dental and postcranial regions of the skeletons of scaphocephalic individuals. PMID- 8476272 TI - Odontometry of Lithuanian paleopopulations. AB - In 3443 teeth of 418 adults (224 males, 194 females) from Lithuanian crania of the 1st and 2nd millennia A.D., vestibulolingual (VL) and mesiodistal (MD) diameters of each tooth were measured on the right side. The samples showed a marked stability during the millennia, measurements being typical for a mesodontic population. Definite sexual dimorphism of teeth measurements was established. A method for sex estimation from dental measurements is proposed. PMID- 8476273 TI - Age estimation from teeth using soft X-ray findings. AB - Soft X-ray photos of 68 premolars and 98 molars from 102 males and 64 females were taken to measure the length (mm) of the corona (CL) and the length of coronal pulp cavity (CPCL). Then the coronal index CI = CPCL x 100/CL after Ikeda et al. (1985) was computed for each tooth and regressed on the actual age of the individuals to obtain equations that allow estimation of age in unknown bodies and isolated teeth. The correlation coefficients ranged from -0.73 (female molars) to -0.89 (female premolars). No significant differences were observed in age estimation using sex-specific equations. PMID- 8476274 TI - Polymorphism of properdin factor B (Bf) in some Italian populations. AB - In order to contribute to the definition of a map of the distribution of Bf polymorphism in Italy, we typed numerous population samples (for a total of 2033 individuals) from several regions of Italy: provinces of Bologna, Potenza and Matera, middle Sangro valley (Chieti) and northern, central and southern Sardinia. A new method was used which consisted of cellulose acetate electrophoresis followed by immunofixation and staining with Coomassie blue. The results obtained highlight marked differences in the distribution of Bf phenotypes and allele frequencies in Italy. To be noted in particular are the relatively high incidence of the Bf*S allele and the low incidence of Bf*F in Potenza and the significantly different pattern of the Sardinian samples compared to those from mainland Italy. This may be due to the low incidence in Sardinia of the Bf*S allele and above all to the exceptionally high frequency of the Bf*F1 variant. PMID- 8476275 TI - Directional and fluctuating asymmetry in the palmar interdigital ridge-counts. AB - Directional and fluctuating asymmetry of the palmar interdigital ridge-counts (c d, b-c and a-b) was evaluated using a sample of 1186 male and 1042 female Germans. The c-d and b-c ridge-counts show higher right side values while the a-b count shows a higher left side value. Sex differences in asymmetry are significant, females exhibiting larger left values than males for all three counts. Directional asymmetries of the different areas exhibit weak negative correlations. Fluctuating asymmetry (magnitude of L-R) is highest for the c-d count, followed by the a-b. Both c-d and a-b ridge-counts exhibit a significant quadratic relationship between magnitude of L-R and R+L, but b-c does not. The quadratic relationship shows that individuals with extreme phenotypes are more asymmetrical than those closer to the mean. This in turn may be interpreted to mean that fluctuating asymmetry is a reflection of developmental stability. PMID- 8476276 TI - Arm folding, hand clasping and dermatoglyphic asymmetry in Bulgarians. AB - Arm folding and hand clasping have been analysed in 2100 Bulgarians, 1050 of either sex. In both traits, significant preponderance of the left type over the right one was revealed. Also, in both traits the excess of the left type is more pronounced in females but this sexual heterogeneity is significant only in the arm folding. Examination of the possible association between arm folding and hand clasping showed the independence between both asymmetries. On the other hand, the comparison between both sexes concerning distributions of the four possible combinations of types revealed statistically significant sexual dimorphism in this respect. Two kinds of dermatoglyphic asymmetry, directional and relative, have been investigated and comparisons have been made between right and left claspers and between right and left folders, each sex separately and finger-by finger. Although statistically significant differences are not numerous, they have been discussed from the point of view of the importance of relationships between functional and morphological asymmetries. PMID- 8476277 TI - [The upper hearing limit. A study of its dependence on age and sex with consideration of endogenous and exogenous factors]. AB - In order to determine the upper limit of the audible frequency range as well as its age-dependency we have examined 198 persons whose ages varied from 3 to 90 years of which 111 were women. To correct for potential errors that might occur due to other factors which may differ from the age only, an additional 28 variables have been recorded besides the measurement of high-tone perception. The hearing experiment was based on the monaural exposition of a monofrequent test signal. Its frequency was continuously varied whereas the sound pressure level was kept as constant as possible. The results show a strong dependency of upper frequency limit at a given sound level with the age and some sex-differences. All the rest of possibly interfering variables (i.e. noise-exposition or ototoxic drugs) remained below the threshold of statistical significance. The approximately linear relationship between the age and the ability of high frequency perception shows a more pronounced and earlier loss of sensitivity (to high frequencies) in males than in females. PMID- 8476278 TI - Effects of acetate, propionate, and butyrate on the thermophilic anaerobic degradation of propionate by methanogenic sludge and defined cultures. AB - The effects of acetate, propionate, and butyrate on the anaerobic thermophilic conversion of propionate by methanogenic sludge and by enriched propionate oxidizing bacteria in syntrophy with Methanobacterium thermoautotrophicum delta H were studied. The methanogenic sludge was cultivated in an upflow anaerobic sludge bed (UASB) reactor fed with propionate (35 mM) as the sole substrate for a period of 80 days. Propionate degradation was shown to be severely inhibited by the addition of 50 mM acetate to the influent of the UASB reactor. The inhibitory effect remained even when the acetate concentration in the effluent was below the level of detection. Recovery of propionate oxidation occurred only when acetate was omitted from the influent medium. Propionate degradation by the methanogenic sludge in the UASB reactor was not affected by the addition of an equimolar concentration (35 mM) of butyrate to the influent. However, butyrate had a strong inhibitory effect on the growth of the propionate-oxidizing enrichment culture. In that case, the conversion of propionate was almost completely inhibited at a butyrate concentration of 10 mM. However, addition of a butyrate-oxidizing enrichment culture abolished the inhibitory effect, and propionate oxidation was even stimulated. All experiments were conducted at pH 7.0 to 7.7. The thermophilic syntrophic culture showed a sensitivity to acetate and propionate similar to that of mesophilic cultures described in the literature. Additions of butyrate or acetate to the propionate medium had no effect on the hydrogen partial pressure in the biogas of an UASB reactor, nor was the hydrogen partial pressure in propionate-degrading cultures affected by the two acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476279 TI - Ecological and genetic analysis of copper and streptomycin resistance in Pseudomonas syringae pv. syringae. AB - Strains of Pseudomonas syringae pv. syringae resistant to copper, streptomycin, or both compounds were recovered from symptomless and diseased tissue of four woody hosts in three nurseries in Oklahoma. In strains resistant to copper and streptomycin (Cur Smr), resistance to both compounds was cotransferred with a single plasmid which was either 68, 190, or 220 kilobase pairs (kb). All Cus Smr strains contained a 68-kb conjugative plasmid. Cur Sms strains contained one plasmid which varied in size from 60 to 73 kb. All conjugative plasmids which transferred streptomycin resistance contained sequences homologous to the strA and strB Smr genes from the broad-host-range plasmid RSF1010. The Smr determinant was subsequently cloned from a 68-kb Cur Smr plasmid designated pPSR1. A restriction map detailing the organization of the homologous Smr genes from pPSR1 and RSF1010 and cloned Smr genes from P. syringae pv. papulans and Xanthomonas campestris pv. vesicatoria revealed the conservation of all sites studied. The Cur genes cloned from P. syringae pv. tomato PT23 and X. campestris pv. vesicatoria XV10 did not hybridize to the Cur plasmids identified in the present study, indicating that copper resistance in these P. syringae pv. syringae strains may be conferred by a distinct genetic determinant. PMID- 8476280 TI - Biodegradation and biotransformation of groundwater pollutant mixtures by Mycobacterium vaccae. AB - Mycobacterium vaccae can catabolize a number of major groundwater pollutants. When added singly, acetone, cyclohexane, styrene, benzene, ethylbenzene, propylbenzene, dioxane, and 1,2-dichloroethylene can be catabolized by M. vaccae. Catabolism of a number of these chemicals was monitored by gas-chromatographic analysis. Gas-chromatographic analysis indicated that the products of benzene degradation are phenol and hydroquinone. The products of chlorobenzene and ethylbenzene degradation are 4-chlorophenol and 4-ethylphenol. The extent that some compounds were catabolized when present as mixtures was also investigated. When toluene and benzene were present concomitantly, toluene was catabolized and benzene oxidation was delayed. Although toluene promoted the degradation of styrene, a lower rate of toluene degradation occurred when styrene was present. Both 4-chlorophenol and 4-ethylphenol had an antagonistic effect on the ability of M. vaccae to degrade other aromatic compounds. Studies with [14C]benzene indicated that M. vaccae can mineralize small amounts of this compound. These results suggest that components in mixtures may have a positive or a negative effect on the rates of biodegradation of other pollutants. PMID- 8476281 TI - Elimination of Escherichia coli O157:H7 in meats by gamma irradiation. AB - Undercooked and raw meat has been linked to outbreaks of hemorrhagic diarrhea due to the presence of Escherichia coli O157:H7; therefore, treatment with ionizing radiation was investigated as a potential method for the elimination of this organism. Response-surface methods were used to study the effects of irradiation dose (0 to 2.0 kGy), temperature (-20 to +20 degrees C), and atmosphere (air and vacuum) on E. coli O157:H7 in mechanically deboned chicken meat. Differences in irradiation dose and temperature significantly affected the results. Ninety percent of the viable E. coli in chicken meat was eliminated by doses of 0.27 kGy at +5 degrees C and 0.42 kGy at -5 degrees C. Small, but significant, differences in radiation resistance by E. coli were found when finely ground lean beef rather than chicken was the substrate. Unlike nonirradiated samples, no measurable verotoxin was found in finely ground lean beef which had been inoculated with 10(4.8) CFU of E. coli O157:H7 per g, irradiated at a minimum dose of 1.5 kGy, and temperature abused at 35 degrees C for 20 h. Irradiation is an effective method to control this food-borne pathogen. PMID- 8476282 TI - Role of growth phase and ethanol in freeze-thaw stress resistance of Saccharomyces cerevisiae. AB - The freeze-thaw tolerance of Saccharomyces cerevisiae was examined throughout growth in aerobic batch culture. Minimum tolerance to rapid freezing (immersion in liquid nitrogen; cooling rate, approximately 200 degrees C min-1) was associated with respirofermentative (exponential) growth on glucose. However, maximum tolerance occurred not during the stationary phase but during active respiratory growth on ethanol accumulated during respirofermentative growth on glucose. The peak in tolerance occurred several hours after entry into the respiratory growth phase and did not correspond to a transient accumulation of trehalose which occurred at the point of glucose exhaustion. Substitution of ethanol with other carbon sources which permit high levels of respiration (acetate and galactose) also induced high freeze-thaw tolerance, and the peak did not occur in cells shifted directly from fermentative growth to starvation conditions or in two respiratorily incompetent mutants. These results imply a direct link with respiration, rather than exhaustion of glucose. The role of ethanol as a cryoprotectant per se was also investigated, and under conditions of rapid freezing (cooling rate, approximately 200 degrees C min-1), ethanol demonstrated a significant cryoprotective effect. Under the same freezing conditions, glycerol had little effect at high concentrations and acted as a cryosensitizer at low concentrations. Conversely, under slow-freezing conditions (step freezing at -20, -70, and then -196 degrees C; initial cooling rate, approximately 3 degrees C min-1), glycerol acted as a cryoprotectant while ethanol lost this ability. Ethanol may thus have two effects on the cryotolerance of baker's yeast, as a respirable carbon source and as a cryoprotectant under rapid-freezing conditions. PMID- 8476283 TI - Biodegradation of a synthetic lubricant by Micrococcus roseus. AB - A bacterium that was able to utilize Emkarate 1550 (E1550), a synthetic lubricant ester, as the sole source of carbon was isolated. The isolate was tentatively identified as Micrococcus roseus. The components of the E1550 ester, octanoate, decanoate, and 1,1,1-tris(hydroxymethyl)propane (TMP), were detected in the culture medium of cells growing on the ester. The TMP tertiary alcohol accumulated during growth and was not utilized by this isolate. The detection of the components of the ester in the supernatant of cultures indicated that one of the first steps in its degradation was cleavage of the ester bonds. Esterase activity was significantly enhanced in cells grown on E1550 compared with esterase activity measured in cells grown on acetate. PMID- 8476284 TI - Dynamics, spread, and persistence of a single genotype of Pseudomonas syringae relative to those of its conspecifics on populations of snap bean leaflets. AB - A rifampin-resistant strain of Pseudomonas syringae (R10) was introduced onto bean plants grown in field plots to examine the processes of growth, spread, and survival of a single genotype relative to the dynamics of its conspecifics on populations of individual leaflets. R10 was applied to four plots (400, 200, 100, and 50 m2), each of which was centered in a quadrant of a bean field (90 by 90 m). Population sizes of the species P. syringae and of R10 were determined on each of 25 individual leaflets collected from the largest plot (A) at approximately weekly intervals during a 10-week period following application. The spread of R10 from all plots was monitored by leaf imprinting of individual leaflets collected at sites along four transects, each of which bisected two of the plots. The introduced strain was a dominant component of the species for about 5 weeks postinoculation on leaflets from plot A. Although the population sizes of R10 remained at about 5.0 to 5.5 log10 CFU per leaflet, the strain became a progressively minor component of the species as the population sizes of its conspecifics continued to increase during the latter part of the growing season. In general, a positive correlation was found for the population sizes of R10 and its conspecifics on individual leaflets collected throughout the growing season. This result suggests that large numbers of R10 early in the growing season did not exclude the colonization of bean leaflets by its conspecifics. It is apparent that the species pool comprised genotypes that were more fit than R10 under the conditions that prevailed during the latter part of the growing season. By 6 weeks postinoculation, R10 was detected at all sites sampled within the unsprayed areas of the field. However, it was present as a minor component of the species. The persistence of R10 throughout the winter and into the following growing season was monitored in plot A, which was plowed and replanted with wheat in the fall. R10 was detected on some of the samples (wheat seedlings or soil) taken at approximately monthly intervals from November to June of the following year. In June, the field was plowed and replanted with beans. We could not detect R10 on emerging bean seedlings in plot A. The results demonstrate that the successful spread and persistence of an introduced bacterium do not necessarily lead to the establishment of large populations of the bacterium in adjacent untreated areas or on its host plant in subsequent growing seasons. PMID- 8476285 TI - Microbial production of D-malate from maleate. AB - To produce D-malate from maleate by a microbial reaction, we screened a number of maleate-utilizing microorganisms for enzyme activity by an intact cell system. The strain which showed the best productivity among the 440 strains tested was identified taxonomically as Arthrobacter sp. strain MCI2612. The optical purity of the malate produced by this strain was 100% D type. The culture and reaction conditions for the production were studied for this strain. Addition of amino acids such as L-proline, L-histidine, and L-arginine to the culture medium promoted the formation of reaction activity as well as cell growth. Under optimum conditions, 87 g of D-malate per liter was produced in 20 h. The yield was 72 mol%. PMID- 8476286 TI - Cloning of a novel cryIC-type gene from a strain of Bacillus thuringiensis subsp. galleriae. AB - A novel cryIC-type gene was isolated from a strain of Bacillus thuringiensis subsp. galleriae. A new polymerase chain reaction (PCR) technique with a set of several oligonucleotide primer pairs specific to the cryIC gene was used to screen a number of B. thuringiensis strains. PCR amplified several DNA fragments ranging from 100 bp to 1 kb for B. thuringiensis strains containing a cryIC gene. PCR fragments amplified from the Bacillus thuringiensis subsp. galleriae HD29 DNA differed from the fragments amplified from other cryIC-containing strains, indicating strain HD29 contained a novel cryIC-type gene. To isolate crystal genes homologous to cryIC, an HD29 gene library was probed with a 984-bp fragment of the amino-terminal coding region of the cryIC gene cloned from Bacillus thuringiensis subsp. aizawai HD229. A putative toxin gene was isolated from a phage that hybridized strongly to the cryIC probe. Translation of the putative toxin DNA sequence revealed an open reading frame of 1,176 amino acids whose predicted molecular mass was 132.8 kDa. Comparisons of the toxin gene sequence with sequences of other cry genes indicated that this gene is a subclass of cryIC. We propose to designate this gene cryIC(b). In Escherichia coli, the cryIC(b) gene produced a protein of approximately 130 kDa toxic to Spodoptera exigua and Trichoplusia ni. PMID- 8476287 TI - Rapid isolation and sequencing of purified plasmid DNA from Bacillus subtilis. AB - We report two methods for isolation of plasmid DNA from the gram-positive bacterium Bacillus subtilis. The protoplast alkaline lysis procedure was developed for general use, and the protoplast alkaline lysis magic procedure was developed for isolation of DNA for sequencing. Both procedures yielded large amounts of high-quality DNA in less than 1 h, while current protocols require 4 to 7 h to perform and give lower yields and quality. Plasmid DNA was obtained from strains containing either high- or low-copy-number plasmids. In addition, the procedures were easily adapted to yield large amounts of plasmid DNA suitable for sequencing from another gram-positive organism, Staphylococcus aureus. Further, we demonstrated that neither chloramphenicol, used for plasmid selection, nor the mutation recE4 reduced plasmid DNA yield from the strains we examined. PMID- 8476288 TI - Detection of Xanthomonas campestris pv. citri by the polymerase chain reaction method. AB - pFL1 is a pUC9 derivative that contains a 572-bp EcoRI insert cloned from plasmid DNA of Xanthomonas campestris pv. citri XC62. The nucleotide sequence of pFL1 was determined, and the sequence information was used to design primers for application of the polymerase chain reaction (PCR) to the detection of X. campestris pv. citri, the causal agent of citrus bacterial canker disease. Seven 18-bp oligonucleotide primers were designed and tested with DNA from X. campestris pv. citri strains and other strains of X. campestris associated with Citrus spp. as templates in the PCR. Four primer pairs directed the amplification of target DNA from X. campestris pv. citri strains but not from strains of X. campestris associated with a different disease, citrus bacterial spot. Primer pair 2-3 directed the specific amplification of target DNA from pathotype A but not other pathotypes of X. campestris pv. citri. A pH 9.0 buffer that contained 1% Triton X-100 and 0.1% gelatin was absolutely required for the successful amplification of the target DNA, which was 61% G+C. Limits of detection after amplification and gel electrophoresis were 25 pg of purified target DNA and about 10 cells when Southern blots were made after gel electrophoresis and probed with biotinylated pFL1. This level of detection represents an increase in sensitivity of about 100-fold over that of dot blotting with the same hybridization probe. PCR products of the expected sizes were amplified from DNA extracted from 7-month old lesions from which viable bacteria could not be isolated. These products were confirmed to be specific for X. campestris pv. citri by Southern blotting. This PCR-based detection protocol will be a useful addition to current methods of detection of this pathogen, which is currently the target of international quarantine measures. PMID- 8476289 TI - Purification of Pseudomonas putida acyl coenzyme A ligase active with a range of aliphatic and aromatic substrates. AB - Acyl coenzyme A (acyl-CoA) ligase (acyl-CoA synthetase [ACoAS]) from Pseudomonas putida U was purified to homogeneity (252-fold) after this bacterium was grown in a chemically defined medium containing octanoic acid as the sole carbon source. The enzyme, which has a mass of 67 kDa, showed maximal activity at 40 degrees C in 10 mM K2PO4H-NaPO4H2 buffer (pH 7.0) containing 20% (wt/vol) glycerol. Under these conditions, ACoAS showed hyperbolic behavior against acetate, CoA, and ATP; the Kms calculated for these substrates were 4.0, 0.7, and 5.2 mM, respectively. Acyl-CoA ligase recognizes several aliphatic molecules (acetic, propionic, butyric, valeric, hexanoic, heptanoic, and octanoic acids) as substrates, as well as some aromatic compounds (phenylacetic and phenoxyacetic acids). The broad substrate specificity of ACoAS from P. putida was confirmed by coupling it with acyl-CoA:6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum to study the formation of several penicillins. PMID- 8476290 TI - Influence of alternative electron acceptors on the anaerobic biodegradability of chlorinated phenols and benzoic acids. AB - Nitrate, sulfate, and carbonate were used as electron acceptors to examine the anaerobic biodegradability of chlorinated aromatic compounds in estuarine and freshwater sediments. The respective denitrifying, sulfidogenic, and methanogenic enrichment cultures were established on each of the monochlorinated phenol and monochlorinated benzoic acid isomers, using sediment from the upper (freshwater) and lower (estuarine) Hudson River and the East River (estuarine) as source materials. Utilization of each chlorophenol and chlorobenzoate isomer was observed under at least one reducing condition; however, no single reducing condition permitted the metabolism of all six compounds tested. The anaerobic biodegradation of the chlorophenols and chlorobenzoates depended on the electron acceptor available and on the position of the chlorine substituent. In general, similar activities were observed under the different reducing conditions in both the freshwater and estuarine sediments. Under denitrifying conditions, degradation of 3- and 4-chlorobenzoate was accompanied by nitrate loss corresponding reasonably to the stoichiometric values expected for complete oxidation of the chlorobenzoate to CO2. Under sulfidogenic conditions, 3- and 4 chlorobenzoate, but not 2-chlorobenzoate, and all three monochlorophenol isomers were utilized, while under methanogenic conditions all compounds except 4 chlorobenzoate were metabolized. Given that the pattern of activity appears different for these chlorinated compounds under each reducing condition, their biodegradability appears to be more a function of the presence of competent microbial populations than one of inherent molecular structure. PMID- 8476291 TI - Some characteristics of a proteinase from a thermophilic Bacillus sp. expressed in Escherichia coli: comparison with the native enzyme and its processing in E. coli and in vitro. AB - Proteinase Ak.1 was produced during the stationary phase of Bacillus sp. Ak.1 cultures. It is a serine proteinase with a pI of 4.0, and the molecular mass was estimated to be 36.9 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme was stable at 60 and 70 degrees C, with half-lives of 13 h and 19 min at 80 and 90 degrees C, respectively. Maximum proteolytic activity was observed at pH 7.5 with azocasein as a substrate, and the enzyme also cleaved the endoproteinase substrate Suc-Ala-Ala-Pro-Phe-NH-Np (succinyl-alanyl-alanyl-prolyl-phenylalanine p-nitroanalide). Major cleavage sites of the insulin B chain were identified as Leu-15-Tyr-16, Gln-4-His-5, and Glu-13-Ala-14. The proteinase gene was cloned in Escherichia coli, and expression of the active enzyme was detected in the extracellular medium at 75 degrees C. The enzyme is expressed in E. coli as an inactive proproteinase at 37 degrees C and is converted to the mature enzyme by heating the cell-free media to 60 degrees C or above. The proproteinase was purified to homogeneity and had a pI of 4.3 and a molecular mass of 45 kDa. The NH2-terminal sequence was Ala-Ser-Asn-Asp Gly-Val-Glu-, showing the exact signal peptide cleavage point. Heating the proenzyme resulted in the production of active proteinase with an NH2-terminal sequence identical to that of the native enzyme. The characteristics of the cloned proteinase were identical to those of the native enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476292 TI - Exopolysaccharide production in biofilms: substratum activation of alginate gene expression by Pseudomonas aeruginosa. AB - Reporter gene technology was employed to detect the activity of an alginate promoter of Pseudomonas aeruginosa when the organism was grown as a biofilm on a Teflon mesh substratum and as planktonic cells in liquid medium. Alginate biosynthetic activity was determined with a mucoid cell line derived from a cystic fibrosis isolate and containing an alginate algC promoter fused to a lacZ reporter gene. Reporter activity was demonstrated with chromogenic and fluorogenic substrates for beta-galactosidase. Expression of algC was shown to be upregulated in biofilm cells compared with planktonic cells in liquid medium. Gene up-expression correlated with alginate biosynthesis as measured by Fourier transform infrared spectroscopy, uronic acid accumulation, and alginate-specific enzyme-linked immunosorbent assay. The algC promoter was shown to have maximum activity in planktonic cultures during the late lag and early log phases of the cell growth cycle. During a time course experiment, biofilm algC activity exceeded planktonic activity except during the period immediately following inoculation into fresh medium. In continuous-culture experiments, conversion of lacZ substrate was demonstrated microscopically in individual cells by epifluorescence microscopy. PMID- 8476293 TI - Enhanced mineralization of polychlorinated biphenyls in soil inoculated with chlorobenzoate-degrading bacteria. AB - An Altamont soil containing no measurable population of chlorobenzoate utilizers was examined for the potential to enhance polychlorinated biphenyl (PCB) mineralization by inoculation with chlorobenzoate utilizers, a biphenyl utilizer, combinations of the two physiological types, and chlorobiphenyl-mineralizing transconjugants. Biphenyl was added to all soils, and biodegradation of 14C Aroclor 1242 was assessed by disappearance of that substance and by production of 14CO2. Mineralization of PCBs was consistently greatest (up to 25.5%) in soils inoculated with chlorobenzoate degraders alone. Mineralization was significantly lower in soils receiving all other treatments: PCB cometabolizer (10.7%); chlorobiphenyl mineralizers (8.7 and 14.9%); and mixed inocula of PCB cometabolizers and chlorobenzoate utilizers (11.4 and 18.0%). However, all inoculated soils had higher mineralization than did the uninoculated control (3.1%). PCB disappearance followed trends similar to that observed with the mineralization data, with the greatest degradation occurring in soils inoculated with the chlorobenzoate-degrading strains Pseudomonas aeruginosa JB2 and Pseudomonas putida P111 alone. While the mechanism by which the introduction of chlorobenzoate degraders alone enhanced biodegradation of PCBs could not be elucidated, the possibility that chlorobenzoate inoculants acquired the ability to metabolize biphenyl and possibly PCBs was explored. When strain JB2, which does not utilize biphenyl, was inoculated into soil containing biphenyl and Aroclor 1242, the frequency of isolates able to utilize biphenyl and 2,5 dichlorobenzoate increased progressively with time from 3.3 to 44.4% between 15 and 48 days, respectively. Since this soil contained no measurable level of chlorobenzoate utilizers yet did contain a population of biphenyl utilizers, the possibility of genetic transfer between the latter group and strain JB2 cannot be excluded. PMID- 8476294 TI - Testing of some assumptions about biodegradability in soil as measured by carbon dioxide evolution. AB - Conversion to CO2 upon incubation in aerobic soil is one of the standard test procedures to assess biodegradability. It may be measured with unlabeled test compounds in biometer flasks. In this case, the background CO2 evolution by unamended soil is subtracted from the CO2 evolution by the amended soil and the resulting net CO2 evolution becomes the measure of biodegradation. Alternately, 14CO2 release from radiocarbon substrates is measured to assess biodegradability. Both approaches measure ultimate (complete) biodegradation and bypass the theoretical and technical limitations of residue analysis. This report examines the underlying assumptions that, except for carbon content, conversion percentage to CO2 is relatively independent of chemical composition, that CO2 production is proportional to the amount of added test compound, and that the background CO2 evolution of the soil is not influenced by the test substance. Work with unlabeled and radiolabeled substrates proved the first two assumptions to be essentially correct. However, more than half of net CO2 production may represent the mineralization of biomass and soil organic matter, some of it unrelated to the test compound. The soil microbial community in its nongrowing steady state appears to convert a much lower percentage of a radiocarbon substrate to 14CO2 than a growing soil community that responds to a substantial substrate addition. These findings may help to improve test methods and may aid in the interpretation of test results. PMID- 8476295 TI - Degradation of poly(3-hydroxyoctanoic acid) [P(3HO)] by bacteria: purification and properties of a P(3HO) depolymerase from Pseudomonas fluorescens GK13. AB - Twenty-five gram-negative bacteria and one gram-positive bacterium capable of growing on poly(3-hydroxyoctanoic acid) [P(3HO)] as the sole source of carbon and energy were isolated from various soils, lake water, and activated sludge. Most of the isolates degraded only P(3HO) and copolymers of medium-chain-length (MCL) hydroxyalkanoic acids (HA). Except for the gram-positive strain, which was able to hydrolyze P(3HO) and poly(3-hydroxybutyric acid) [P(3HB)], no isolate was able to degrade polymers of short-chain-length HA, such as P(3HB) or poly(3 hydroxyvalerate) [P(3HV)]. All strains utilized a large variety of monomeric substrates for growth. All gram-negative strains, but not the gram-positive strain, accumulated poly(hydroxyalkanoic acids) (PHA), consisting of MCL HA, if they were cultivated under accumulation conditions. One strain, which was identified as Pseudomonas fluorescens GK13 (biovar V), was selected and the extracellular P(3HO) depolymerase of this strain was purified from the culture medium of P(3HO)-grown cells by chromatography with Octyl-Sepharose CL4B and by gel filtration with Superose 12. The relative molecular weights of the native and sodium dodecyl sulfate-treated enzymes were 48,000 and 25,000, respectively. The purified enzyme hydrolyzed P(3HO), copolymers of MCL HA, and para-nitrophenyl esters of fatty acids. P(3HB), P(3HV), and characteristic substrates for lipases, such as Tween 80 or triolein, were not hydrolyzed. The P(3HO) depolymerase of P. fluorescens GK13 was insensitive to phenylmethylsulfonyl fluoride and dithioerythritol, unlike other PHA depolymerases. The dimeric ester of 3 hydroxyoctanoic acid was identified as the main product of enzymatic hydrolysis of P(3HO).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476296 TI - Biodegradability and mechanical properties of poly-(beta-hydroxybutyrate-co-beta hydroxyvalerate)-starch blends. AB - Wheat starch granules and poly-(beta-hydroxybutyrate-co-beta-hydroxyvalerate) [P(HB-co-HV), (19.1 mol% HV)] were blended at 160 degrees C. Increasing the starch content from 0 to 50% (wt/wt) decreased the tensile strength of P(HB-co HV) from 18 MPa to 8 MPa and diminished flexibility as Young's modulus increased from 1,525 MPa to 2,498 MPa, but overall mechanical properties of the polymer remained in a useful range. A mixed microbial culture required more than 20 days to degrade 150-microns-thick samples of 100% P(HB-co-HV), whereas samples containing 50% (wt/wt) starch disappeared in fewer than 8 days. Starch granules degraded before P(HB-co-HV) did. Aerobic degradation proceeded more rapidly than anaerobic degradation. PMID- 8476297 TI - Expression and secretion of Bacillus amyloliquefaciens alpha-amylase by using the yeast pheromone alpha-factor promoter and leader sequence in Saccharomyces cerevisiae. AB - Replacement of the regulatory and secretory signals of the alpha-amylase gene (AMY) from Bacillus amylolique-faciens with the complete yeast pheromone alpha factor prepro region (MF alpha 1p) resulted in increased levels of extracellular alpha-amylase production in Saccharomyces cerevisiae. However, the removal of the (Glu-Ala)2 peptide from the MF alpha 1 spacer region (Lys-Arg-Glu-Ala-Glu-Ala) yielded decreased levels of extracellular alpha-amylase. PMID- 8476298 TI - Rapid identification of bacteria on the basis of polymerase chain reaction amplified ribosomal DNA spacer polymorphisms. AB - To facilitate genus and species level identification of a broad range of bacteria without the requirement of presumptive identification, we have developed a unified set of primers and polymerase chain reaction conditions to amplify spacer regions between the 16S and 23S genes in the prokaryotic rRNA genetic loci. Spacer regions within these loci show a significant level of length and sequence polymorphism across both genus and species lines. A generic pair of priming sequences was selected for the amplification of these polymorphisms from highly conserved sequences in the 16S and 23S genes occurring adjacent to these polymorphic regions. This single set of primers and reaction conditions was used for the amplification of 16S-23S spacer regions for over 300 strains of bacteria belonging to eight genera and 28 species or serotypes, including Listeria, Staphylococcus, and Salmonella species and additional species related to these pathogenic organisms. When the spacer amplification products were resolved by electrophoresis, the resulting patterns could be used to distinguish all of the species of bacteria within the test group. Unique elements in the amplification product patterns generally clustered at the species level, although some genus specific characteristics were also observed. On the basis of the results obtained with our test group of 300 bacterial strains, amplification of the 16S-23S ribosomal spacer region is a suitable process for generating a data base for use in a polymerase chain reaction-based identification method, which can be comprehensively applied to the bacterial kingdom. PMID- 8476299 TI - Secondary metabolites resulting from degradation of PR toxin by Penicillium roqueforti. AB - PR toxin is a secondary metabolite of the fungus Penicillium roqueforti. It is lethal to rats, mice, and cats. Usually, the amount of PR toxin in the culture medium decreases from its maximum on day 15 to zero within 3 to 4 days. We found that two were secondary metabolites produced in the culture medium of this fungus while the production of PR toxin was decreasing. We isolated and purified the two compounds in pure and colorless crystalline form. On the basis of elemental analysis and mass, 1H and 13C nuclear magnetic resonance, infrared, and UV spectroscopies, the two compounds were identified as PR-imine (C17H21O5N) and PR amide (C17H21O6N). The structures of both compounds and of PR toxin (C17H20O6) were closely related, and the peak production of PR toxin appeared earlier than those of PR-imine and PR-amide. Moreover, PR toxin was transformed to PR-imine when PR toxin was incubated with the culture medium on a given culture day. Thus, we propose that PR toxin is degraded into PR-imine and PR-amide in the culture medium of P. roqueforti. PMID- 8476300 TI - Colonization of broiler chickens by waterborne Campylobacter jejuni. AB - Chickens on a broiler farm in southern England were found to be colonized with Campylobacter jejuni of a single serotype, Lior 1 Penner 4. The farm was the sole supplier of a local slaughterhouse associated with a campylobacter outbreak in 1984 caused by this serotype. The serotype persisted on the farm for at least 18 months after the outbreak; its prevalence in the human population served by the farm remained high until it disappeared from the farm in 1986. The possible sources and routes of transmission of C. jejuni to the broilers on the farm were investigated. The results showed that vertical transmission, feed, litter, small mammals, and environmental or airborne cross-contamination between sheds or successive crops could be excluded as persistent sources of C. jejuni. The predominant source of C. jejuni on the farm was shown to be the water supply. Direct microscopy and fluorescent antibody methods revealed presumptive campylobacters throughout the farm's water system. Campylobacter-free chickens raised in an animal house and given water from the farm supply became colonized with the serotype of C. jejuni endemic on the farm (Lior 1 Penner 4). An intervention program based on water chlorination, shed drinking system cleaning and disinfection, and withdrawal of furazolidone from feed reduced the proportion of birds colonized with campylobacter from 81 to 7% and was associated with a 1,000- to 10,000-fold reduction in campylobacters recoverable from the carcasses. Two months after the end of the intervention program colonization of the birds returned to high levels (84%), indicating that there was a temporal association between intervention and reduced colonization with C. jejuni. Investigations continue to establish the general applicability of these findings. PMID- 8476301 TI - Quality of community drinking water and the occurrence of late adverse pregnancy outcomes. AB - The relationship between community drinking water quality and the occurrence of late adverse pregnancy outcomes was investigated by conducting a case-control study among women who delivered infants during August 1977 through March 1980 at Brigham and Women's Hospital in Massachusetts. The water quality indices were compared among 1,039 congenital anomaly cases, 77 stillbirth cases, 55 neonatal death cases, and 1,177 controls. Trace element levels were gathered from routine analyses of public water supplies from the communities in which the women resided during pregnancy. It was observed that, after adjustment for confounding, the frequency of stillbirths was increased for women exposed to chlorinated surface water (OR 2.6 95% CI 0.9-7.5) and for women exposed to detectable lead levels (OR 2.1; 95% CI 0.6-7.2); the frequency of cardiovascular defects was increased relative to detectable lead levels (OR 2.2, 95% CI 0.9-5.7); and the frequency of central nervous system defects was increased relative to the highest tertile of potassium (OR 6.3, 95% CI 1.1-37.3). The frequency of ear, face, and neck anomalies was increased in relation to detectable silver levels (OR 3.3, 95% CI 0.9-12.2), but the frequency decreased relative to high potassium levels (OR 0.2, 95% CI 0.1-0.7). The frequency of neonatal deaths was decreased relative to detectable fluoride levels (OR 0.4, 95% CI 0.2-1.0), and the frequency of musculoskeletal defects was decreased relative to detectable chromium levels (OR 0.4, 95% CI 0.2-1.0). The majority of these associations were not stable statistically. Further research is needed to corroborate these findings. PMID- 8476302 TI - Exposure misclassification due to residential mobility during pregnancy in epidemiologic investigations of congenital malformations. AB - This study addressed the question of how maternal migration between conception and birth affects estimates of risk in studies of congenital malformations when movement is related to the exposure. For example, in studying the potential association between proximity to a chemical waste site and the occurrence of birth defects, incorrect inferences might be drawn if maternal residence at birth was used as a surrogate for exposure at conception in the case when a significant amount of media attention influenced some women to move away from the site after becoming pregnant. A simple statistical model is proposed that defines the distance to a fixed exposure point measured at birth as a function of the distance to the point measured at conception, the probability of movement, the direction of movement, and the distance moved. Bias is the difference between the expected results when distance is measured at birth versus conception. The amount of bias can be substantial for movement patterns that may be likely to occur. This simplified model was used in an effort to explore and better understand the relationships between maternal migration and risk. PMID- 8476303 TI - Hepatitis A epidemics from utility sewage in Ocoee, Florida. AB - The 1988-1989 hepatitis A epidemic in the Palms section of Ocoee, Florida, followed sewage overflows and involved 39 cases and a fetal death. Of the 18 index cases (i.e., the first hepatitis illness in a household), each had a history of contact with sewage-contaminated stormwater and no other known contact with the infection. Illnesses varied from mild to severe; 20 people reported that diarrhea, abdominal pain, varying degrees of ascites, and other symptoms continued for 2 y after the initial illness. Health injuries up to 20 y of lost life, measured by CEA-Clinical Epidemiological AnalysisSM, were found. Public records of rainfall and sewage flows provide evidence of massive stormwater entry into the utility system, which periodically appears to have flushed sewage from the utility lift station into residential areas. PMID- 8476304 TI - Lead and child development. PMID- 8476305 TI - Lead and child development. PMID- 8476307 TI - Bronchial responsiveness to methacholine in swine confinement building workers. AB - Bronchial responsiveness to methacholine was measured in 60 swine confinement building workers selected from 461 subjects who participated in a recent epidemiologic survey on the respiratory impact of exposure to this environment. Subjects were divided into the following four groups: group 1, asymptomatic with normal spirometry (n = 16); group 2, asymptomatic with forced expiratory volume in one second/forced vital capacity (FEV1.0/FVC) < 95% predicted (n = 17); group 3, presence of chronic bronchitis with normal respiratory function (n = 13); and group 4, both symptomatic and FEV1.0/FVC < 95% predicted (n = 14). Each subject answered a questionnaire and had a physical examination, PA and lateral chest films, lung volumes and DLCO measurements, and a methacholine bronchoprovocation test. Ages were similar in each group. Physical examination, chest x-rays, and DLCO were normal in all subjects. Values of total lung capacity (TLC) for subjects in group 4 were higher than those of subjects in group 3, and respiratory volume (RV) values of group 4 subjects were higher than those found for all other groups. The provocation dose of methacholine (PC20) was lower for group 4, and the number of subjects with PC20 < 16 mg/ml was greater in this group than in the other groups. We conclude that only swine confinement building workers with both symptoms of chronic bronchitis and abnormal spirometry have an increased bronchial responsiveness to methacholine; however, it is uncertain whether the bronchial responsiveness demonstrated is directly related to the subjects' employment. PMID- 8476306 TI - Lung cancer: a prospective study of smoking, occupation, and nutrient intake. AB - A cohort study of lung cancer was conducted among 7,961 Japanese-American men who were interviewed and examined during 1965-1968. Information was collected about their smoking history, occupation, and nutrient intake. After 22 y, 227 incident cases of lung cancer were identified. Cigarette smoking significantly increased lung cancer risk. The relative risk (RR) was 3.1 for past smokers and 11.4 for current smokers, compared with never smokers. We separated lung cancer cases according to histological type, and it was found that current smokers had a RRs of 16.0 for squamous/small-cell carcinoma and 6.8 for adenocarcinoma of the lung. Unskilled manual workers had a significantly higher risk (RR = 1.5; 95% confidence interval, 1.1-2.2) for lung cancer than workers who were engaged in nonmanual occupations. There was no association between lung cancer and the 24-h intake of total calories, protein, fat, dietary cholesterol, carbohydrates, and alcohol, but this may have resulted from the limitations of a 24-h dietary questionnaire. PMID- 8476308 TI - Paraquat poisoning in southern Mexico: a report of 25 cases. AB - Paraquat is a bipyridyl herbicide used world-wide. Although accidental and deliberate ingestions of lethal doses have been reported from many countries, no case has ever been described in Mexico. The authors report on 25 cases of Paraquat poisoning in the state of Chiapas, Mexico, that occurred between 1988 and 1990. Eighty percent of the cases were men, and 64% of the cases died. Alcohol intoxication or suicidal intent were factors at the time of Paraquat ingestion in 75% of the cases. The majority of cases had learned to use Paraquat from a friend; none had been instructed by a professional. Eighty percent of cases did not know the dilution for the proper use of the herbicide, and none kept the herbicide in its original container. Attention to the law, redesign of the Paraquat packaging, and educational efforts directed at populations at risk might reduce the occurrence of poisoning in this region. PMID- 8476309 TI - Toxicological and immune findings in workers exposed to pentachlorophenol (PCP). AB - Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls. PCP concentrations were determined in plasma and urine of all subjects. Lymphocyte subsets of CD3-, CD4-, and CD8 positive cells were evaluated, and the proliferative response of peripheral blood mononuclear cells (PBM) to mitogens was assessed. The results suggested the absence of major laboratory and clinical signs of PCP-dependent immune deficiency. A weak effect of long-term exposure to PCP on the functional immune response could not be ruled out because of the finding of a decreased response to 5% PHA in the high-exposure group. A weak effect against hepatocyte membrane was evidenced by the finding of raised serum concentration of glycocholic, taurodeoxycholic, and glycochenodeoxycholic acids in subjects directly exposed to PCP for more than 10 y. PMID- 8476310 TI - A case-control study of carcinomas of the nose and paranasal sinuses in the woolen textile manufacturing industry. AB - A population-based case-control study was conducted in Biella, which is located in northwestern Italy, to investigate the reported association between sinonasal carcinomas and woolen fabrics production. The study included 33 cases diagnosed during 1976-1988 (14 adenocarcinomas, 11 epidermoid carcinomas, 3 other specified carcinomas, 1 unspecified carcinoma, and 4 cases without histologic confirmation) and 131 controls. No association was found with smoking. As reported previously, excess risks were observed in wood and furniture workers (odds ratio [OR] = 4.4, 95% confidence interval [95% CI] = 1.41-13.4) and in the leather industry (OR = 3.5, 95% CI = 0.6-20.3). Odds ratios in the wood and furniture industry were 22.0 (95% CI = 4.4-124.0) for adenocarcinomas and 0.9 (95% CI = 0.4-8.3) for epidermoid carcinomas. No association was found with the woolen textile or garment industries (OR = 0.8, 95% CI = 0.2-2.8), nor with farming, construction, metal works, and transport. Odds ratios for the textile industry did not vary with length of exposure or histologic type. Power for detecting an odds ratio of 3.0 at the 95% level of significance was 40%. PMID- 8476312 TI - Positive connectedness in the psychiatric nurse-patient relationship. AB - Positive connectedness in the psychiatric nurse-patient relationship is believed to enhance the effectiveness of the therapeutic relationship. The psychiatric nurse's experience of connectedness to patients is examined in this study, and factors contributing to the development of a positive connectedness are explored using structured interviews. PMID- 8476311 TI - Environmental exposure and lifestyle predictors of lead, cadmium, PCB, and DDT levels in Great Lakes fish eaters. AB - A previously characterized cohort of 115 Great Lakes fish eaters and 95 non-fish eating regional controls was reexamined in 1989. Levels of blood lead and cadmium and serum PCB and DDT were measured. Lifestyle characteristics, including recent and historic fish consumption, were evaluated as predictors of contaminant levels using multivariate regression analysis. Significantly elevated serum PCB and DDT levels were observed in fish eaters, compared with controls. Historic fish consumption, rather than recent consumption, was identified as the primary predictor of current serum levels. Mean blood lead and cadmium were also significantly higher in fish eaters than in controls. However, the primary predictors of lead and cadmium were behavioral exposures--specifically smoking and self-reported occupational and recreational exposure-rather than fish consumption. These findings illustrate the importance of evaluating a variety of possible sources when investigating human exposure to environmental contaminants. PMID- 8476313 TI - Nursing diagnoses for psychiatric patients in China. AB - This report describes the development of a preliminary Chinese psychiatric classification system with nine categories and 211 separate diagnoses, and the corresponding diagnostic interview that enables psychiatric nurses in China to systematically assess the presence or absence of the various diagnoses. Using this interview with 30 representative inpatients, the authors identified 152 of the 211 (72%) diagnoses. On average, each patient was given 26 different nursing diagnoses. The interrater reliability of the four nurses who independently coded the diagnostic interview for these 30 patients was excellent: in over 77% of the identified diagnoses the generalized kappa was greater than 0.75. These findings show that further work on this classification of nursing diagnoses is warranted. PMID- 8476314 TI - Nursing staff and patient perceptions of the ward atmosphere in a maximum security forensic hospital. AB - The purpose of this study is to describe the factors influencing nursing staff and patients' perceptions of the ward atmosphere in a maximum security forensic hospital. The study used the Ward Atmosphere Scale to identify specific factors. Findings indicate that structure and compliance with ward routine and behavioral standards are the most important factors in perceptions of the ward atmosphere. Also, despite the emphasis on security and the ever-present potential for violence, nursing staff were able to maintain a therapeutic ward atmosphere. PMID- 8476315 TI - Social factors and depression in late life. AB - Depression is a common mental health problem facing the elderly that is often overlooked and subsequently untreated by health care professionals. Recognition of the problem can be aided by knowledge of the causes or at least the factors associated with it. Identification of specific social factors has important implications for geropsychiatric nursing practice, education, and research. The major social factors associated with depression in late life are reviewed. The contributions of social factors to the onset, course, and duration of depression are presented. Future research directions are also discussed. PMID- 8476316 TI - Is there life after suicide? The systemic belief approach for "survivors" of suicide. AB - Following suicide of a loved one the lives of survivors can be plagued with anger, sadness, shame, guilt, health problems, and agonizing questions. This report presents the Systemic Belief approach to assisting survivors. A case example illustrates the influence beliefs have on survivors' lives. Constraining beliefs are challenged and facilitative beliefs are coevolved through the healing impact of family systems nursing interventions such as therapeutic letters, interventive questions, rituals, and reflecting teams. PMID- 8476317 TI - [Critical review of the bibliographic references of "Archivos Espanoles de Urologia"]. AB - Due to the lack of Spanish journals or publications with a rather strong "impact", which is basically determined by the number of times a publication is cited, we attempted to corroborate the widely held view that very little reference is made to the Spanish literature. On analyzing all the articles published in "Archivos Espanoles de Urologia" during 1990 (182 articles with a total of 3,324 references), we found that only 13.61% of the references were from Spanish journals, books or Congresses held in Spain, which dropped to 10.3% if the books or communications delivered at meetings are excluded. Approximately 30% of the articles did not have a single reference from a Spanish publication. Furthermore, the articles submitted by foreigners rarely included any reference from the Spanish literature. Finally, the Journal of Urology (USA), which accounted for over 20% of the references, was the most cited. PMID- 8476318 TI - [Renal oncocytoma]. AB - We report on three cases of renal oncocytoma that had been diagnosed and treated between 1986 and 1991. We underscore the difficulty in making the differential diagnosis from a renal adenocarcinoma and its higher incidence. Anatomopathological studies undertaken retrospectively have contributed further insight into its histological features and have shown it to be less uncommon. PMID- 8476319 TI - [Verrucous carcinoma of the penis: our caseload]. AB - Verrucous carcinoma, a tumor that encompasses approximately 5% of all penile neoformations, is a variant of squamous cell carcinoma which is benign and has a peculiar histological behaviour. We report on three patients aged 57, 80 and 84 years with this tumor type who underwent surgery (circumcision in one case and partial penectomy in the remaining two cases). The literature is briefly reviewed and the epidemiological, clinical, diagnostic and therapeutic aspects are discussed. PMID- 8476320 TI - [Distal urethral obstruction in girls: a diagnosis to keep in mind]. AB - Although obstruction of the distal urethra is uncommon in the female, it should not be discarded if the patient is a young girl who consults for symptoms as diverse as enuresis, frequency and urgency, urinary infections, etc. Such a case is reported herein. The patient underwent internal urethrotomy which resolved the obstruction and eliminated the symptoms. PMID- 8476321 TI - [Post-vasectomy semen in 313 males. Statistical analysis, medical aspects, legal implications]. AB - The results of semen examination in 313 vasectomized males are presented. A quantitative analysis of the semen samples was performed according to the WHO criteria and the centrifugate of the entire ejaculate was studied. At the first semen examination, which was performed three months after the procedure, the sperm count per ml was negative in 210 patients (83.7%), positive (all non-motile and dead) in 41 (16.3%). Sixty-two patients did not send a sample. Those cases with a positive first examination had a regular examination every two months. At five months 90.8% of these cases had a negative count per ml. 3.6% of the patients required 7-10 months to have a negative count. It took longer for the older patients to have a negative count, the difference being statistically significant with respect to the younger patients. Examination of the centrifugate revealed spermatozoa in 24.3% of the samples with a negative sperm count per ml, although these were all non-motile and dead, except for one case who had motile spermatozoa at 3 months. There were no pregnancies or revasectomies. Some legal aspects relative to patient examination and follow-up are discussed. PMID- 8476322 TI - [Experience with the determination of LDH-X in seminal plasma as diagnostic and prognostic factor in varicocele]. AB - We studied the biochemical and functional properties of semen to evidence markers of diseases concerning fertility. We examined LDH especially isoenzyme LDHx in semen of patients with varicocele, diagnosed by clinical evaluation and doppler velocimetry. The existence of this enzyme is closely associated with active spermatogenesis. In conditions of testicular disease as in varicocele, a major diffusion of LDHx into the seminal plasma may occur as a reaction of the seminiferous epithelium. We evaluated 50 patients (10 normospermic patients, 20 affected by varicocele, 9 azoospermic patients, 11 oligo-astenospermic patients). We observed that the LDHx concentration in seminal plasma is proportional to the severity of the clinical damage. The follow up after spermatic vein ligation of the patients affected by varicocele demonstrated that these patients improved to the normal clinical parameters, associated to a decrease of the concentration of LDHx values. PMID- 8476323 TI - [Hydraulic dilatation of urethral stenosis controlled with ultrasonography. A new approach]. AB - The present study describes the ultrasound control of water dilatation for urethral stenosis. In our view, the door is open to future developments of water dilatation protocols for urethral strictures. PMID- 8476324 TI - [Renal adenocarcinoma in the isthmus of a horseshoe kidney]. AB - A case of renal adenocarcinoma localized to the isthmus of a horseshoe kidney is described. We underscore the importance of complementary US and/or CT to urography to study the acquired pathologies of the horseshoe kidney because the pyelocaliceal distribution of these kidneys may not facilitate correct identification of certain space occupying lesions. The angiographic study is considered essential for planning surgery for this type of lesion. PMID- 8476325 TI - [Angioma of the glans, report of 2 cases]. AB - We present two cases of angioma of the glans penis and we reviewed this disease entity from a clinical and therapeutic points of view, classically understood as a proliferative process of a malformative nature. However, both cases that are described can be interpreted as true vascular tumors of a benign nature. PMID- 8476326 TI - [Spontaneous extravasation of urine at the pyelo-caliceal level. Spontaneous urinomas]. AB - We present two cases of spontaneous rupture of the excretory tract within the context of reno-ureteral colic due to lithiasis. We comment on the etiopathogenic aspects and underscore the need for emergency evaluation in patients with very severe nephric colic and/or symptoms of peritoneal irritation (ileus, abdominal guarding), and temporary urinary diversion must be performed via nephrostomy as a palliative procedure for the symptoms and to avoid complications. PMID- 8476327 TI - [Transitional cell neoplasm of the bladder in childhood: presentation of a clinical case]. AB - A case of urothelial carcinoma of the bladder in a 13-year-old boy is reported. As observed in the literature, it is an extremely rare condition in children. The importance of gross or microscopic hematuria, which is often the only sign of this condition, is underscored. The authors comment on the possible follow-up modalities in relation with the characteristics of this tumor type in young patients. Although it is more invasive (anesthesia, trauma) than US or urinary cytology, cystoscopy is more precise. Because recurrence is extremely rare, it can be performed once a year. PMID- 8476328 TI - [Trigeminal neuralgia. First manifestation of adenocarcinoma of the prostate]. AB - We report a case of adenocarcinoma of the prostate that had been incidentally discovered during patient evaluation for trigeminal nerve neuralgia refractory to treatment. Analysis revealed the underlying cause of neuralgia was tumor metastasis to the mandible, which had caused irritation of the fifth nerve. The patient was treated with complete androgenic block and his symptoms improved simultaneously with partial remission of metastasis. PMID- 8476329 TI - [Spontaneous rupture of excretory tract caused by calculous impact]. AB - Herein we describe a case of spontaneous rupture of the fornix with urinary extravasation, an uncommon urological condition arising from a sudden increase of intraluminal pressure due to a calculus in the terminal ureter. The etiopathogenesis, follow-up and therapeutic approach are discussed. PMID- 8476330 TI - [Tumor growth fraction and its relationship with morphology of transitional carcinoma of the bladder]. AB - Papillary transitional cell carcinoma of the bladder (PTCCB) is characterized by a high recurrence rate with infiltration of bladder wall and surrounding tissues. The outcome is poor in 10-20% of the cases and these cannot be detected by conventional methods. Different methods have been utilized to identify this high risk patient group, such as the tumor growth factor (TGF). This is obtained with the KI-67 antibody, which identifies a nuclear protein in the cells in the active cellular cycle (G1, G2, S and mitosis). TGF represents the percentage of KI-67 positive tumor cells. The aims of the present study were: 1) to determine the correlation of the histological features and TGF in PTCCB; 2) to determine the percentage, if any, of superficial low grade lesions with a high TGF. Thirty-one transurethral biopsies of patients with PTCCB were analyzed to determine the histological grade (following the criteria described by Ash), wall infiltration (according to the IUAC criteria) and TGF (using the PAP technique). The study revealed 16 (52%) were low grade and 15 (48%) were high grade tumors, 20 (64.5%) were superficial (PTa-PT1), 9 (29%) were deep (PT1-PT4) and the degree of wall infiltration could not be determined in two cases. Of the 20 superficial tumors, 15 (75%) had a low (0-15%) and 5 (25%) had a high (> or = 16%) TGF. The 9 cases with deep infiltration of the bladder wall (PT2-PT4) had a high TGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476331 TI - Modulith SL20--development and clinical experience. AB - A third generation lithotripter was developed incorporating the advantages of high disintegrative efficacy, anaesthesia-free treatment, combined sonographic and fluoroscopic localization system as well as a multifunctional table for interdisciplinary use. The shock wave generator consists of a cylindrical-shaped electromagnetic coil with a paraboloid reflector. The waves are coupled by means of a water cushion and an impedance adapted foil in which the patient is comfortably positioned. Stones are localized by an in-line ultrasound probe or fluoroscopically by the integrated C-arm. Preclinical trials using the in-vitro stone model demonstrated the superior disintegrative capacity. The in-vivo animal studies evaluated the dose-dependent and reversible kidney trauma, which was comparable to that induced by other lithotripters. The clinical evaluation of the Modulith SL since 1988 was divided into three phases with different technical equipment. It was indicated that sonographic stone localization enables treatment of nearly all kidney stones and 12% of the ureteric calculi. As preference was given to in situ disintegration of all ureteral stones, X-ray targeting became necessary. By increasing the generator voltage in the third phase together with advanced experience, the disintegration rate (94%) was improved. The number of auxiliary measures after ESWL (11%) and treatment time (average 39 min) was decreased. Eighty-eight percent of our patients were stone-free at follow-up. The experience demonstrated that this lithotripter is also easy to handle for gallbladder stones and highly effective (82%) in treatment of endoscopically non extractable bile duct stones. PMID- 8476332 TI - Patterns of sexuality in a high-risk sample: results from a survey of new intakes at a county jail. AB - Described the sexual habits and behaviors in a sample of individuals thought to be at high risk for infection with the AIDS virus. The sample is drawn from new arrestees at a county jail in the San Francisco Bay Area. Results indicate that the individuals in this sample are very sexually active: The majority began their sexual activities at a young age; most are currently in a primary relationship; and a large proportion report having had two or more sexual partners in the last 12 months. Furthermore, for the most part, the patterns of sexual behavior reported by respondents did not differ on the basis of gender. Although it was true that men tended to initiate intercourse at an earlier age than women, men and women did not differ with respect to the numbers of sexual partners reported in the last year, frequency of vaginal intercourse, frequency of anal intercourse, or in the distribution of sexual risk-taking. Overall, women in this sample are very much like men in terms of their sexual behavior. PMID- 8476333 TI - Ambiguous stimuli: sex is in the eye of the beholder. AB - It is usually assumed that sexual material is easily identifiable by its content. The present study investigated whether subjects could be led to interpret ambiguous material as sexual or not via simple instructions. Thematically ambiguous written text was presented to 269 subjects. The principal independent variable was the content of advance information. Advance information was designed to suggest that the accompanying text had either a sexual or a nonsexual theme. After reading the story and completing an intervening task, subjects completed recall and recognition tasks based on the text. These data were used to determine the theme or story interpretation given by subjects. The information contained in the advance organizers influenced subjects' memories for and interpretations of the ambiguous story. When the story was preceded by introductory information that suggested sexual content, subjects tended to attribute sexual meaning to the story. Other subjects attributed a nonsexual meaning to the same text when it was preceded by nonsexual information. Findings suggest that under certain conditions, sex is in the "eye of the beholder." PMID- 8476334 TI - Orgasm in the postoperative transsexual. AB - The dearth of information regarding organism in postoperative transsexuals prompted the authors to study its prevalence. The sample consisted of 14 male-to female (M-F) and 9 female-to-male (F-M) postoperative transsexuals. The relationship of orgasm to sexual and general satisfaction was explored via a specially designed questionnaire. Orgastic capacity declined in the M-F group and increased in the (F-M) group. Despite the decrease in orgasm in the M-F group, satisfaction with sex and general satisfaction with the results of surgery were high in both groups. General satisfaction of 86% replicates other studies. Frequency of sex increased by 75% in the M-F group and by 100% in the F-M group. A phalloplasty does not appear to be a critical factor in orgasm or in sexual satisfaction. The general conclusion is reached that it is possible to change one's body image and sexual identity and be sexually satisfied despite inadequate sexual functioning. PMID- 8476335 TI - A factor analysis of the Klein sexual orientation grid in two disparate samples. AB - Many researchers interested in sexual orientation can be separated into two camps: The "lumpers," who try to reduce sexual classifications to as small a number of categories as possible, and the "splitters," who try to show differences among groups and individuals that make classification schemes increasingly difficult and/or intricate. We report factor analyses of the Klein Grid (a questionnaire with 21 sexual orientation items) to see how many factors emerge in two samples of strikingly different origins. In both samples, the first factor to emerge loaded substantially on all of the Klein Grid's 21 items. This factor accounted for a majority of the variance. In both samples, a second, correlated factor emerged which indexed a separation between most of the items and those having to do with social and/or emotional preferences. In both samples, a third correlated factor also emerged, but this factor differed between the two populations: one refined the social/emotional distinction and the other distinguished ideal behavior from past and current behavior. We conclude on the basis of our analysis that both the lumpers and the splitters are correct. PMID- 8476336 TI - Gender differences in masturbation and the relation of masturbation experience in preadolescence and/or early adolescence to sexual behavior and sexual adjustment in young adulthood. AB - A comparison of male and female masturbation practices was undertaken in a sample of university students to determine if the long-standing finding that young adult men in this country masturbate more than young adult women was still evident in the 1980s. Despite the efforts in the past quarter century to encourage women in our society to take greater responsibility for their own bodies and their own sexuality and to engage in more sexual self-exploration and self-stimulation, results show that women continue to masturbate much less than men. Twice as many men as women had ever masturbated and the men who masturbated did so three times more frequently during early adolescence and young adulthood than the women who masturbated during these same age periods. A second purpose of this study was to determine whether having masturbation experience during preadolescence and/or early adolescence was related to intercourse experience, sexual satisfaction, sexual arousal, or sexual difficulties in relationships during young adulthood. No such linkage was observed, suggesting that early masturbation experience is neither beneficial nor harmful to sexual adjustment in young adulthood. PMID- 8476337 TI - Effects of antihypertensive drugs atenolol and nifedipine on sexual function in older men: a placebo-controlled, crossover study. AB - Investigated the adverse sexual effects of two antihypertensive drugs, atenolol and slow-release nifedipine, in a placebo-controlled, randomized, crossover study. Subjects were 16 older men (mean age = 66.6 years, SEM = 1.4) with mild to moderate hypertension. Subjects completed daily self-reports on 13 measures of sexuality: frequency of desire, coitus, noncoital partner sex, masturbation, morning erections, spontaneous erections, orgasms in coitus and masturbation, firmness of morning, masturbatory and coital erections, and subjective pleasure in coitus and masturbation. Except for a significant decrease in masturbatory erectile firmness with nifedipine therapy, variables did not differ between the two drug treatments or between either drug and placebo. Although the sample was relatively small, small differences between treatment means suggest that these antihypertensive agents are fairly benign relative to sexual function in men. PMID- 8476338 TI - Palatal and mandibular arch morphology in 47,XYY men and in other sex-chromosome anomalies. AB - Dimensions of the maxilla and mandible were studied in 47,XYY men and their first degree male relatives, and the results compared with similar studies of other sex chromosome anomalies. An extra Y chromosome in 47,XYY men caused an increase in palatal growth transversely and anteroposteriorly and in mandibular arch length anteroposteriorly compared to normal men. Palatal height and mandibular width were smaller with this chromosome pattern. Increase in the number of sex chromosomes is associated with changes in palatal and mandibular arch dimensions, more often an increase than a decrease. The findings support earlier observations that the palate becomes shallower with the addition of an X chromosome. It is also apparent that the influence of X and Y chromosomes differs, at least regarding the magnitude of metric changes. PMID- 8476339 TI - The effect of different strontium concentrations on the efficacy of chlorhexidine fluoride-strontium gel in preventing enamel softening in vitro. AB - The effects were compared of strontium concentrations of 0, 15, 50 and 250 parts/10(6) in chlorhexidine(0.20%)-fluoride(0.16%) gel in preventing the softening of bovine enamel during bacterial fermentation. Fresh Streptococcus sobrinus cells were suspended in a buffer solution (pH 6.0) with 3.3% sucrose and centrifuged as a plaque-like layer on the top of enamel slabs covered with 10 microliters gel. AFter 24 h incubation, the pH fall of the fluid was significantly smaller in all test groups than in the placebo group. Strontium seemed to have an inhibitory effect on the pH fall. All test gels significantly prevented softening and dissolution of enamel during bacterial fermentation, which was directly related to strontium concentration. The amounts of calcium and phosphorus in the cells and fluid after incubation were the smallest in the group with 250 parts/10(6) strontium. In a second experiment without bacteria, new enamel slabs were covered with 10 microliters gel containing chlorhexidine and NaF with 0 and 250 parts/10(6) strontium to study the protective effect of strontium. After 24 h gel treatment, each enamel slab was dissolved in 1 ml 0.1 M lactic acid, pH 5.0, for 2 h. Significantly less calcium and phosphorus were dissolved from the enamel in both test groups than in the control and placebo groups. However, the placebo gel also prevented calcium and phosphorus dissolution significantly. These results suggest that the addition of strontium to chlorhexidine-fluoride gel improves the ability of this combination to prevent caries-like enamel softening. The inhibition of bacterial acid production by the strontium-containing gel may explain this enhanced protection of enamel. PMID- 8476340 TI - Digastric muscle response as a function of knowledge of the task to be performed. AB - Whether the motor programme executed by the digastric muscles during a forceful bite is modified according to a subject's expectation that the resistance between the teeth will change was investigated. There were two experimental conditions: (1) tracking a ramp (drawn on an oscilloscope screen) by biting (isometrically) on a force transducer and holding it at 120 N, and (2) tracking the same ramp with a sudden unloading at 100 N. There were two groups of experiments: (1) control experiments in which subjects underwent a sudden and unexpected unloading of the jaw, and (2) experiments in which subjects were previously informed whether or not there was to be an unloading. In all experiments the subjects co contracted their digastric muscles during the bite as compared to the state at rest. The subjects' responses fell into the three different types: (i) those who varied the level of tonic digastric activity only as a function of the experimental condition, (ii) those who co-contracted the digastric muscles at the same time as the masseter muscles, and (iii) those who changed the contraction pattern of the digastric muscles as a function of the experimental condition. If modulation of the digastric muscles occurred this is a 'feedforward' strategy mainly based on immediate past performance. PMID- 8476341 TI - Glossopharyngeal-hypoglossal nerve reflex of the frog in metamorphosis. AB - In adult frogs, a reflex discharge is elicited from the hypoglossal nerve by mechanical and chemical stimuli to the centre of the tongue surface and electrical stimuli to the glossopharyngeal nerve innervating tongue. However, there has been no report concerning the embryological stage at which this reflex develops. The metamorphosis of a frog is divided into three parts, premetamorphic, metamorphic and climax stage. In the climax stage, the forelimbs are lengthened and the tail gradually shortened. The glossopharyngeal-hypoglossal nerve reflex arose in the early climax stage, during which the tongue appeared on the floor of the mouth. At this stage, the conduction velocities of the first compound action potential of the glossopharyngeal and hypoglossal nerves were about 8.7 and 9.3 m/s, respectively. The latency of the reflex was long, especially the central latency. The response of the glossopharyngeal nerve and the reflex discharge from the hypoglossal nerve upon mechanical stimulation of the tongue were smaller in the tadpole than in the adult frog. As metamorphosis proceeded, the conduction velocity of these nerves increased; the latency shortened, especially the central latency; the reflex response to mechanical stimulus increased. These results suggest that, although the glossopharyngeal hypoglossal nerve reflex is developed in the early climax stage, it is completed only in the adult frog. Therefore, adult frogs living mainly on land may reject and swallow prey by this reflective tongue movement. PMID- 8476342 TI - Cariogenic potential of pooled plaque fluid from exposed root surfaces in humans. AB - The composition of pooled plaque fluid from exposed root surfaces of five population samples was determined before and at selected times (3, 7 and 15 min) after a 5 and 10% sucrose rinse. Subjects were 45-65 yr old, had exposed, sound root surfaces, and were grouped according to root caries status [caries-free (CF), no root caries history; caries-positive (CP), recorded root caries experience]. Samples were obtained only from the sound surfaces of the CF and CP subjects after overnight fasting. Plaque samples from each subgroup were pooled under mineral oil and maintained on ice. Plaque fluid was then isolated by centrifugation and analysed for organic acids and inorganic ions (ion chromatography), and pH (microelectrodes). From these data, the degree of saturation [DS(TM)] in plaque fluid with respect to tooth mineral (TM) was calculated. Before exposure to sucrose, plaque fluids from the CF and the CP subgroups had similar ionic compositions. These fluids were also found to be supersaturated with respect to tooth mineral. After exposure to sucrose, a rapid decrease in plaque fluid pH was observed, which corresponded primarily to lactic acid production. For all times examined, mean pH and DS(TM) values were lower and lactic acid concentrations were higher in the CP than the CF samples. Lower values of DS(TM) suggest that plaque fluid from CP subjects had a measurably greater cariogenic potential. Calcium concentrations also increased significantly and to comparable levels in all plaque fluid samples after sucrose exposure, despite lower acid production in CF samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476343 TI - A thin bite-force transducer with three-dimensional capabilities reveals a consistent change in bite-force direction during human jaw-muscle endurance tests. AB - The construction of a 2 mm-thick bite-force transducer, capable of measuring the magnitude and direction of a bite force in three dimensions, is described. The transducer is programmed to display the properties of a bite force on a computer monitor. A preliminary study was designed to test its performance. This took the form of endurance tests on three human subjects: the test was repeated on one subject. The direction of a sustained maximum incisal bite force was monitored while subjects clenched for as long as possible on the transducer. The initial bite force was directed about 10-15 degrees forward of the vertical. During the test the magnitude of the bite force was kept roughly constant but, for all four tests, its direction gradually changed until at the failure point it was nearly vertical. The consistency of the results suggests that the transducer is sufficiently accurate to be a useful tool for studying human jaw mechanics. PMID- 8476344 TI - Retardation of mouse odontoblast differentiation by heparin in vitro. AB - The effect of heparin was studied histologically and immunohistochemically. Tooth germs from 15-day-old mouse embryos were cultured with or without heparin. After 6 days of culture in control medium, mesenchymal cells underlying the inner enamel epithelium had differentiated into odontoblasts and secreted predentine. In medium with heparin, mesenchymal cells were undifferentiated. In medium with other glycosaminoglycans such as chondroitin sulphate, dermatan sulphate or hyaluronate, tooth germs were similar to those in control medium, as were those in medium with heparin-Sepharose absorbed serum. After 12 days of culture in the heparin medium, mesenchymal cells in some cusps had differentiated into odontoblasts and secreted predentine but in other cusps remained undifferentiated. Immunohistochemically, exogenous heparin did not prevent the deposition of type IV collagen, laminin and fibronectin in the basement membrane and extracellular matrix. These results suggest that exogenous heparin retards differentiation of odontoblasts but not by disruption of the basement membrane nor inactivation of heparin-binding growth factors present in serum. PMID- 8476345 TI - A comparison between sieving and optical scanning for the determination of particle size distributions obtained by mastication in man. AB - Mixtures of particles of different sizes, as obtained after chewing, were analysed. Coarse, medium and fine mixtures of particles of an artificial (Optosil) test food were used. Mixtures of Optosil particles of known form and size (half-cubes) were used to validate the analytical methods. The results of both methods were described by particle size distributions based on the volume of the particles. Complete agreement between methods was found for the mixtures of half-cubes. In order to determine the median particle size by volume from the results of optical scanning an assumption on the form of the chewed particles had to be made. Using the assumption that, on average, the particles resemble spheres a slight overestimate of the median particle size was obtained for scanning as compared to sieving. It can be concluded that, although different aspects of the fragmented particles are measured, sieving and optical scanning are both adequate methods for quantifying mixtures of chewed food particles and yield similar results for the degree of particle size reduction. PMID- 8476346 TI - A comparison between data analysis methods concerning particle size distributions obtained by mastication in man. AB - Three mixtures of chewed food particles (coarse, medium and fine) were quantified by measuring the particle sizes with an optical scanning device. The particle sizes were described by three different particle-size distributions: a cumulative volume, a volume and a number distribution. The median particle size was determined from each of the distribution functions. Suitability for characterizing a mixture of chewed food particles was tested, showing that the median particle size as obtained from a cumulative volume (or weight) distribution should be preferred. It was shown to be the most sensitive measure for characterizing mixtures of chewed food. PMID- 8476347 TI - Diverse firing properties of single motor units in the inner and outer portions of the guinea pig anterior digastric muscle. AB - Microwire recordings from the histochemically heterogeneous inner compartment of the guinea pig anterior digastric muscle (ADG) revealed tonic firing of single motor units, which were spontaneously active and could also be recruited following orofacial afferent stimulation and during rhythmic jaw movements (RJM). As units with tonic firing were not observed in the homogeneously fast-twitch outer ADG, the tonic units were classified as slow-twitch motor units. Irregular patterns of motor-unit firing at variable frequencies were observed after orofacial stimulation and during RJM in the outer and inner compartments. The irregular firing pattern of units in the fast-twitch outer compartment was characterized by shorter and less variable bursts than that of units in the heterogeneous inner compartment. A phasic, centrally driven firing pattern was observed during RJM in outer and inner ADG units. The firing frequency of some of these units was modulated during the rhythmical bursts. It is suggested that, as in limb muscles, functionally specialized ADG motor units are recruited in an orderly sequence, starting with spontaneously active, slow-twitch units in the inner compartment, continuing with fast-twitch units recruited upon enhancement of the synaptic drive (as in the case of orofacial stimulation), and ending with massive, rhythmical recruitment of slow- and fast-twitch units during RJM. PMID- 8476348 TI - Comparative cephalometric analysis in patients with X-chromosome aneuploidy. AB - The influence of abnormal sex-chromosome constitution on cranial growth, shape and position of the craniofacial structures was analysed. Reduced cranial growth was found in women with Turner's syndrome (45 XO chromosome constitution) and in men with Klinefelter's syndrome (47 XXY chromosome constitution). Lack of or an extra X chromosome produced opposite effects on cranial-base flexion, jaw displacement and maxillary and mandibular inclination to the anterior cranial base. An extra X chromosome affected deviation in sagittal jaw relation while lack of an X chromosome influenced mandibular shape. PMID- 8476349 TI - Effects of retinol on the temporal expression of transforming growth factor-alpha mRNA in the embryonic mouse mandible. AB - Development of the mouse embryonic mandible from days 9 to 14 involves tissue interactions in the formation of bone, cartilage, salivary glands and teeth. Growth factors may play an important role in these interactions. Epidermal growth factor (EGF) mRNA expression has been characterized and its presence has been shown to be necessary for odontogenesis. In addition, retinol alters the pattern of dental lamina formation; this effect is correlated with an alteration of the expression of the mRNA for this mitogen (EGF). Transforming growth factor-alpha (TGF alpha) mRNA expression has now been characterized by polymerase chain reaction for this entire period of development (days 9-14). Although the mRNA is present at the same time as EGF (days 9 and 10 only), retinol does not alter the expression of this mitogen as it does EGF. This suggests that retinoids may act to control the proliferative pattern of the dental lamina through EGF expression and not TGF alpha expression, although mRNAs for both mitogens are present at the same time. PMID- 8476350 TI - Frequency selectivity in noise-damaged cochleas. AB - Measures of auditory threshold and masked threshold were obtained at six audiometric test frequencies along with cochleograms on a total population of 363 noise-exposed chinchillas. Seventy animals were chosen from this sample and were separated into five relatively homogeneous groups based upon the amount of permanent threshold shift and sensory cell losses the animals incurred. Tuning curve (TC) metrics were compared to the mean preexposure TC metrics for each group and to the reference preexposure TC metrics obtained from the sample of 363 animals. These data show that in animals with relatively little hearing loss changes in TC metrics can provide evidence for noise-induced sensory cell losses and that the low frequency slope of the TC is a sensitive index of trauma. PMID- 8476351 TI - Progressive hearing loss in hard-of-hearing children. AB - A group of 92 children with bilateral sensorineural hearing loss has been followed up over a period of up to 15 years from the time that an initial reliable audiogram was obtained. This group was studied in order to determine the frequency of occurrence of progressive hearing loss and the relationship of the progressive to the presumed etiology of hearing loss. Progression of hearing loss was demonstrated in 21 children out of the 92 children studied. This progression of hearing loss was either bilateral or unilateral, and no evident relationship could be found between the presumed etiology of hearing loss and its progressivity. PMID- 8476352 TI - Structure of perceived handicap in middle-aged males with noise-induced hearing loss, with and without tinnitus. AB - By using a modified stepwise regression analysis technique, the structure of self perceived handicap and tinnitus annoyance in 89 males with noise-induced hearing loss was described. Handicap was related to three clusters of variables, reflecting individual, environmental, and socioeconomic aspects, and 60% of the variance in self-perceived handicap was explained by the representatives of these clusters: i.e. 'acceptance of hearing problems', 'social support related to tinnitus' and 'years of education'. Tinnitus had no impact of its own on self perceived handicap and only a modest portion (36%) of the variance in tinnitus annoyance was explained by 'sleep disturbance' and 'auditory perceptual difficulties'. PMID- 8476353 TI - Test-retest variability of the auditory brainstem response to bone-conducted clicks in newborn infants. AB - The variability of the auditory brainstem response (ABR) to bone- and air conducted clicks was investigated utilizing a test-retest paradigm with 20 normal full-term newborn infants. ABRs to bone-conducted clicks at 15 and 30 dB nHL and air-conducted clicks at 30 dB nHL were obtained. The delivery of the bone conducted signal was controlled. ABR wave V latencies were measured from each test-retest stimulus condition. The results indicated no statistically significant difference in test-retest variability of ABR wave V latencies or amplitudes between bone- and air-conducted clicks. ABRs to bone-conducted clicks, under controlled clinical conditions, are as reproducible and reliable as ABRs to air-conducted clicks in newborn infants. PMID- 8476354 TI - Normal infant and adult auditory brainstem responses to bone-conducted tones. AB - Auditory brainstem responses (ABRs) were recorded to 500- and 2000-Hz bone conducted (BC) tones from normal infants and adults. Infant ABR thresholds for the 500-Hz BC tones are significantly lower than their thresholds to 2000-Hz BC tones. Infant wave V latencies to 500-Hz BC tones are significantly shorter than those of adults, whereas infant and adult responses to 2000-Hz BC tones are similar in latency, suggesting that the effective intensity of the BC tones may be 9-17 dB greater for infants than for adults. A marked asymmetry between the ipsilaterally and contralaterally recorded wave V is seen for infant responses to 500- and 2000-Hz tones at all intensities; this asymmetry is not as evident in adults, except near threshold. PMID- 8476355 TI - Resistance to synthetic pyrethroids in South Australian populations of sheep lice (Bovicola ovis). AB - Lice were collected from 71 flocks detected as infested at market inspection in 1990 and 1991, from 16 flocks where resistance was suspected and from 31 flocks from Kangaroo Island. Susceptibility to cypermethrin was measured by a treated surface technique and survival of lice at 5 ppm or greater was taken as an indication of resistance. The prevalence of resistance was 34% in louse populations from the market inspection sample, 50% in flocks in which resistance was suspected and 68% in flocks from Kangaroo Island. Most resistance factors were in the range 1 to 20 although one louse population with a resistance factor of 91 was found on Kangaroo Island. PMID- 8476356 TI - Evaluation of an ultrasonic Doppler probe for pregnancy diagnosis in cattle. AB - The use of an ultrasonic Doppler probe for pregnancy diagnosis was evaluated. Data from the examination of 1115 cattle were analysed. Comparison of the probe with manual rectal palpation by an experienced clinician yielded a sensitivity of 92.8 +/- 1.6% (+/- 95% confidence interval) and a specificity of 75.8 +/- 7.4%. This level of accuracy was found to be insufficient to recommend the probe be used by farmers for the diagnosis of pregnancy. PMID- 8476357 TI - The surgical correction of a deviated anterior maxilla in a horse. AB - The surgical correction of facial deformities of the horse have rarely been undertaken. The surgical and medical management of submucous clefting of the anterior maxilla in a young colt is described. PMID- 8476358 TI - Intestinal parasites in dogs from an aboriginal community in New South Wales. PMID- 8476359 TI - Survival by sheep body lice (Bovicola ovis) after plunge dipping in synthetic pyrethroid lousicides. PMID- 8476360 TI - Diagnosis of highly pathogenic avian influenza in chickens: Bendigo 1992. PMID- 8476361 TI - Early history of veterinary education in Victoria. PMID- 8476362 TI - The threat of rabies introduction and establishment in Australia. PMID- 8476363 TI - Polymerase chain reaction and other laboratory techniques in the diagnosis of long incubation rabies in Australia. AB - Blood and post-mortem tissues from a 10-years-old girl were submitted to the Australian Animal Health Laboratory. Clinical signs and histopathological lesions had suggested a diagnosis of rabies, but, an unusually long incubation period of at least 5 years did not encourage such a diagnosis. Serological examinations by the rapid fluorescent focus inhibition test revealed a dramatic increase in rabies virus-neutralising antibody during the 10-day period of hospitalisation. The results of a fluorescent antibody test on brain smears, and an immunoperoxidase test on formalin-fixed sections of brain were also consistent with a diagnosis of rabies. Attempts to isolate virus were unsuccessful. Polymerase chain reactions (PCRs) were conducted on a 10% suspension of a post mortem sample from the patient's brain, using primers based on the published sequence of the Pasteur virus strain of rabies virus. 413 and 513 bp fragments from the nucleoprotein gene and a 403 bp fragment from the glycoprotein gene were amplified. Subsequent sequencing of these fragments, and comparison with equivalent regions of known rabies viruses, confirmed that the fragments originated from a virus belonging to the rabies virus serotype. This case demonstrated the advantage of using a range of laboratory techniques to obtain a definitive diagnosis. In particular, a PCR-based test may allow a diagnosis, even in the face of conditions that preclude virus isolation such as apparently occurred in this case. Finally, this case demonstrated that an unusually long incubation period should not discourage a tentative clinical diagnosis of rabies. PMID- 8476364 TI - The incidence and severity of intercarpal ligament damage in the equine carpus. AB - The arthroscopic findings in 104 intercarpal joints in 76 horses were reviewed to determine the incidence and severity of changes in the medial intercarpal ligament. Damage to the intercarpal ligament was observed in 43 joints in 35 horses, ranging from mild fraying of the edges of the ligament to complete disruption of all fibres. This represented an incidence of 41% of joints being affected. In 9 joints examined arthroscopically primarily as a further diagnostic procedure, ligament damage was evident in all cases. In horses undergoing arthroscopic surgery primarily for the treatment of osteochondral chip or slab fractures, there was some correlation between the severity of articular cartilage damage and the presence of ligament damage. PMID- 8476365 TI - Restriction-endonuclease analysis of Australian isolates of Leptospira interrogans serovar hardjo from cattle with agalactia and abortion. AB - Polyacrylamide gel electrophoresis and agarose gel electrophoresis were used to resolve restriction endonuclease digests of 20 Australian Isolates of Leptospira interrogans cultured from urine samples of cattle with agalactia and abortion. The restriction endonuclease profiles of 19 isolates closely matched the profiles of L interrogans serovar hardjo subtype hardjobovis reference strains. The remaining isolate had a different restriction profile from subtype hardjobovis and subtype hardjoprajitno reference strains and was serologically identified as serovar pomona. Silver staining of polyacrylamide gels gave enhanced resolution of restriction fragments compared with the traditional method of ethidium bromide staining of agarose gels. PMID- 8476366 TI - Body fluid alterations during head-down bed rest in men at moderate altitude. AB - To determine the effects of hypoxia on fluid balance responses to simulated zero gravity, measurements were made in six subjects (acclimatized to 5,400 ft; 1,646 m) before and during -5 degrees continuous head-down bed rest (HDBR) over 8 d at 10,678 ft. The same subjects were studied again at this altitude without HDBR as a control (CON) using a cross-over design. During this time, they maintained normal upright day-time activities, sleeping in the horizontal position at night. Fluid balance changes during HDBR in hypoxia were more pronounced than similar measurements previously reported from HDBR studies at sea level. Plasma volume loss (-19% on day 6) was slightly greater and the diuresis and natriuresis were doubled in magnitude as compared to previous studies in normoxia and sustained for 4 d during hypoxia. These changes were associated with an immediate, but transient rise in plasma atrial natriuretic peptide (ANP) to day 4 of 140% in HDBR and 41% in CON (p < 0.005), followed by a decline towards baseline. Differences were less striking between HDBR and CON for plasma antidiuretic hormone and aldosterone, which were transiently reduced by HDBR. Plasma catecholamines showed a similar pattern to ANP (+122%) in both HDBR and CON, suggesting that elevated ANP and catecholamines together accounted for the enhanced fluid shifts with HDBR during hypoxia. PMID- 8476367 TI - Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia. AB - To determine the effects of hypoxia on physiological responses to simulated zero gravity, cardiopulmonary and fluid balance measurements were made in 6 subjects (acclimatized to 5,400 ft) before and during 5 degrees head-down bed rest (HDBR) over 8 d at 10,678 ft and a second time at this altitude as controls (CON). The VO2max increased by 9% after CON, but fell 3% after HDBR (p < 0.05). This reduction in work capacity during HDBR could be accounted for by inactivity. The heart rate response to a head-up tilt was greatly enhanced following HDBR, while mean blood pressure was lower. No significant negative impact of HDBR was noted on the ability to acclimatize to hypoxia in terms of pulmonary mechanics, gas exchange, circulatory or mental function measurements. No evidence of pulmonary interstitial edema or congestion was noted during HDBR at the lower PIO2 and blood rheology properties were not negatively altered. Symptoms of altitude illness were more prevalent, but not marked, during HDBR and arterial blood gases and oxygenation were not seriously effected by simulated microgravity. Declines in base excess with altitude were similar in both conditions. The study demonstrated a minimal effect of HDBR on the ability to adjust to this level of hypoxia. PMID- 8476368 TI - Effects of 28-day isolation (ESA-ISEMSI'90) on blood pressure and blood volume regulating hormones. AB - The aim of this study was to determine what effects social isolation and confinement stress had on the volume regulating hormones. In six healthy male subjects, during a 28-d isolation and confinement study (ESA-ISEMSI'90), hematocrit, blood pressure and resting heart rate, plasma cortisol, renin, aldosterone, arginine vasopressin levels besides the electrolyte (Na+, K+) balance and plasma creatinine were measured. During the confinement, an elevated systolic blood pressure (p < 0.01) was observed together with an increase in MHPG corresponding to an elevated mental work load. The pattern displayed by volume regulating hormones (increased values for renin, aldosterone (p < 0.05) and arginine vasopressin) was not only characteristic of confinement stress but also reflected changes in the water and electrolyte metabolism. The increased creatinine levels seen throughout the study were regarded as consequences of hypohydration, and an enhanced muscular catabolism due to reduced physical activity. A similar pattern of hormone modifications was obtained in a head down tilt of the same duration, indicating that some of the described modifications are probably related to isolation and confinement stress. PMID- 8476369 TI - Changes in body fluid compartments during hypohydration and rehydration in heat acclimated tropical subjects. AB - Body fluid compartments at different levels of graded hypohydration and partial rehydration were determined using radiotracers in 28 heat-acclimated, male volunteers from tropical regions of India, in hot dry conditions in a climatic chamber. These subjects were hypohydrated to varying degrees (i.e., 1%, 2%, 3%, and 4% body mass deficit) by moderate work in hot conditions in a climatic chamber maintained at 45 degrees C dry bulb temperature and 30% relative humidity. Rehydration study was carried out only in those subjects who were hypohydrated to 3% and 4% body mass and who were brought back to 2% level of hypohydration by receiving a calculated amount of water. Up to the 2% level of hypohydration, a major contribution towards sweat loss was observed from the interstitial fluid (ISF) compartment. At higher levels of hypohydration, no further significant loss from ISF was seen, though significant losses in intracellular fluid (ICF) and plasma volume (PV) were apparent. The present study also found that at the 4% hypohydration level, a maximum fluid contribution was met by the ICF compartment. Significant increases observed in sweat K+ at 3 and 4% also indicate the ICF mobilization, which is rich in K+ ions. On partial rehydration, the ISF compartment held the repletion fluid in excess, and was found to be enough to restore sweat rate to euhydration level. This study clearly indicates that sudorific gain is achieved with partial restoration alone in subjects hypohydrated to 3 and 4% levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476370 TI - Postural stabilization on a moving platform oscillating at high frequencies. AB - The effect of a fore-aft oscillating platform on postural stability was studied in nine healthy volunteers. The force platform technique was used with automatic analysis that evaluated the position of the center point of force as a function of time. The duration of stimulation lasted 90 s and the perturbation frequencies ranged from 8 to 24 Hz, and were given at constant rms acceleration of 4 m/s2. When compared with a vibration-free baseline stance, horizontal vibration of the platform caused significantly worse postural stability in all subjects. Test frequencies of 8 and 10 Hz produced greater sway velocities than perturbation at frequencies of 14 and 16 Hz. The results indicate that horizontal perturbation of the support surface leads to postural instability that is frequency-dependent. PMID- 8476371 TI - Muscle mitochondrial density after exhaustive exercise in dogs: prolonged restricted activity and retraining. AB - The effect of exhaustive treadmill exercise on mitochondrial density (MD) and ultrastructural changes in quadriceps femoris muscle was studied in 7 normal, healthy, male mongrel dogs (2-4 years, 15-20 kg) before and after restricted activity (RA) (2 months for 5 dogs, 5 months for 2 dogs), and following a subsequent 2-month exercise retraining period (2-months group). Mean (+/- S.E.) time to exhaustion in the 2-month group decreased from 177 +/- 11 min before to 90 +/- 16 min (delta = -49%, p < 0.05) after RA; retraining increased tolerance to 219 +/- 36 min (delta = +24%, p < 0.05) above the pre-RA and 143% (p < 0.05) above the post-RA time. Post-RA exhaustion time in the 5-months group was 25 and 45 min (35 +/- 10 min). Muscle samples taken after RA showed abnormalities indicative of degeneration, which were reversed by retraining. Resting MD decreased (p < 0.05) from a control level of 27.8% to 14.7% (2 months) and 16.3% (5 months), and was restored to 27.1% (NS) after retraining. Exhaustive exercise caused an increase in MD under control conditions and after RA, but not following retraining. Disruption of mitochondria after exercise was evident after 5-months confinement. Factors causing mitochondrial changes and eventually their disruption during exercise after restricted activity are not related as much to the state of fatigue as to the pre-exercise quality of the muscle modified by disease or training. PMID- 8476372 TI - Alcoholism and treatment in airline aviators: one company's results. AB - Airline transport pilots are at risk for alcoholism, although prevalence statistics are not known. (Alcoholism is used to mean alcohol dependence as defined in DSM-III-R.) Whether their prevalence of alcoholism is consistent with that of the general population's, less, or possibly enhanced by psychological vulnerabilities, is considered. However, the development and implementation of this job-based, peer-oriented alcohol treatment can be an asset to pilot career progression and airline pilot retention. According to a retrospective analysis of identified aviators, 87% of alcoholic pilots of this major airline returned to flight duties after substance abuse treatment. Relapse occurred in 13% of those accepting treatment. Early identification and treatment of the substance-abusing aviator can be enhanced by encouraging teamwork between pilots, union, airline management, flight surgeons, and employee assistance program professionals. PMID- 8476373 TI - Unregulated self-medication in an ambulatory surgery population. AB - The objective of this study was to determine whether unregulated self-medication in an ambulatory surgery population was a significant problem in terms of the incidence and nature of drugs detected. We asked 67 consecutive patients who presented for elective ambulatory surgery at a university medical center to volunteer for serum and urine testing with the assurance of confidentiality. All patients denied nonprescription drug use. Initial testing was for amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine (PCP), tetrahydrocannabinol (THC) and alcohol. Of the 64 patients who agreed to be tested, 16 patients tested positive for at least one of the above substances; 4 patients demonstrated residua of 2 or 3 substances. No distinctive characteristic of those with evidence of drug use could be identified. We believe that the 25% of patients who tested positive in this group is a conservative estimate of possible unrecognized drug use. We have demonstrated a significant incidence of substance abuse in the ambulatory surgery environment. These findings have serious safety implications, and a higher awareness of possible nonprescription drug use in this environment is needed in medical and support personnel. PMID- 8476374 TI - Bibliographic guide to publications in aerospace medicine and related topics. AB - This bibliographic guide is a comprehensive listing of international publications (books) in Clinical Aerospace Medicine, Operational Aerospace Medicine, Aerospace Physiology, Environmental Medicine/Physiology, Diving Medicine/Physiology, Aerospace Human Factors, as well as other important topics directly or indirectly related to aerospace medicine. This guide will be useful as a primary source of consultation for bibliographic information; especially to those colleagues who are in their formative years, and to those who do not have easy access to computer-aided literature search systems. This bibliographic guide does not constitute a recommendation or an endorsement of any of the publications listed herein and the merits or limitations of each publication should be judged by the reader. PMID- 8476375 TI - Cases from the aerospace medicine residents' teaching file. Case #53. Retained renal calculi. PMID- 8476376 TI - A survey of blood lipid levels of airline pilot applicants. PMID- 8476377 TI - Chronic effects of trimipramine, an antidepressant, on hippocampal synaptic plasticity. AB - The effects of trimipramine (TRIM), an antidepressant agent, on both the induction and the maintenance of long-term potentiation (LTP) was investigated in area CA1 of hippocampal slice preparations. Chronic administration (7-9 days) of TRIM in rat caused a large reduction in the magnitude of LTP induced by a theta burst stimulation (TBS) paradigm. Results indicate that the reduction of LTP produced by trimipramine does not seem to result from major changes in the physiological properties of the slice preparations. First, paired-pulse facilitation was not impaired following the drug administration suggesting that transmitter release was not modified in TRIM-treated slices. Second, the burst responses evoked by high-frequency stimulation exhibited the typical buildup of depolarization, which is due to both a reduction of IPSPs and the activation of NMDA receptors. Finally, the treatment did not change the amount of short-term potentiation induced by TBS nor did it modify the component of excitatory postsynaptic potentials (EPSPs) mediated by the activation of NMDA receptors, suggesting that the NMDA receptor functions remained intact in TRIM-treated slices. Taken together the present data suggest that the loss of LTP maintenance in TRIM-treated animals is more likely the result of the disruption by trimipramine of cellular processes that follow LTP induction. In addition, the results provide evidence for a possible correlation between the reduction in LTP expression and learning deficits produced by chronic administration of trimipramine. PMID- 8476378 TI - Continuous recognition of spatial and nonspatial stimuli in hippocampal-lesioned rats. AB - The present experiments compared the performance of hippocampal-lesioned rats to control rats on a spatial continuous recognition task and an analogous nonspatial task with similar processing demands. Daily sessions for Experiment 1 involved sequential presentation of individual arms on a 12-arm radial maze. Each arm contained a Froot Loop reinforcement the first time it was presented, and latency to traverse the arm was measured. A subset of the arms were repeated, but did not contain reinforcement. Repeated arms were presented with lags ranging from 0 to 6 (0 to 6 different arm presentations occurred between the first and the repeated presentation). Difference scores were computed by subtracting the latency on first presentations from the latency on repeated presentations, and these scores were high in all rats prior to surgery, with a decreasing function across lag. There were no differences in performance following cortical control or sham surgery. However, there was a total deficit in performance following large electrolytic lesions of the hippocampus. The second experiment employed the same continuous recognition memory procedure, but used three-dimensional visual objects (toys, junk items, etc., in various shapes, sizes, and textures) as stimuli on a flat runway. As in Experiment 1, the stimuli were presented successively and latency to run to and move the object was measured. Objects were repeated with lags ranging from 0 to 4. Performance on this task following surgery did not differ from performance prior to surgery for either the control group or the hippocampal lesion group. These results provide support for Kesner's attribute model of hippocampal function in that the hippocampus is assumed to mediate data-based memory for spatial locations, but not three-dimensional visual objects. PMID- 8476379 TI - Social condition affects the courtship behavior of male ring doves with posterior medial hypothalamic lesions. AB - Following bilateral lesions to the posterior medial hypothalamus (homologue of the mammalian ventromedial nucleus), adult male ring doves regain full courtship behavior and the ability to stimulate female egg-laying when housed continuously with females. Males with PMH lesions housed singly and only tested periodically with females continue to show deficits in courtship. These findings suggest that the social environment present in adulthood itself can directly influence recovery from brain lesions. They also demonstrate the importance of PMH in the mediation of male ring dove courtship behavior. PMID- 8476380 TI - Spontaneously hypertensive rats (SHR) readily learn to vary but not repeat instrumental responses. AB - When spontaneously hypertensive rats (SHR) and Wystar-Kyoto normotensive control rats (WKY) were rewarded in a 12-arm radial maze (Experiment 1), the SHRs varied their arm choices more, making fewer repetition errors than the WKYs. Similarly when rewards depended on variable sequences of responses on two levers in an operant chamber (Experiment 2), SHRs' sequences were more variable than those of WKYs. A requirement for response variability was then combined with a requirement to repeat selected responses in the radial maze (Experiment 3) and operant chamber (Experiment 4). WKYs learned to repeat more readily than the SHRs, whereas SHRs varied more readily. Thus, when subjects had to repeat responses, SHRs were at a disadvantage, but when variability was adaptive, SHRs excelled. The high variability of SHRs, together with their difficulty in learning to repeat, may have parallels in children diagnosed with attention deficit disorder with hyperactivity (ADDH). PMID- 8476381 TI - Alterations to the pattern of ultrasonic calling after prenatal exposure to aluminium sulfate. AB - Pregnant CBA mice were exposed to aluminium sulfate at a dose of 200 mg/kg body wt injected intraperitoneally during Days 10 to 13 of gestation. We used a variety of ethological measures, which have been shown to be sensitive indicators of toxicants, to assess effects on the mother and the behavioral development of pups. Prenatal aluminium resulted in a reduction in the rate of ultrasonic calling by pups accompanied by a shift in the timing of peak calling; treated pups exhibited decreased growth and delays in neurobehavioral development. The treatment received by a pup's foster mother was also found to influence development. We recommend ultrasonic calling as a sensitive measure in studies of behavioral teratogenicity. PMID- 8476382 TI - D-cycloserine attenuates scopolamine-induced learning and memory deficits in rats. AB - The muscarinic antagonist scopolamine (SCOP; 1.0 mg/kg, ip) impaired both the acquisition of a learning task in the Morris water maze (MWM) and choice accuracy in the T-maze reinforced alternation procedure in rats. Acetylcholinesterase inhibitors (AChEIs) have been shown to attenuate these deficits. D-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine site on the N methyl-D-aspartate (NMDA) receptor complex, was investigated for its effects on SCOP-induced dementia in the MWM and T-maze paradigms. Combined administration of SCOP and DCS (3.0, 10.0, or 30.0 mg/kg, ip; 30 min pretreat) significantly reversed SCOP-induced deficits in the T-maze as measured by percentage correct choices. In addition, DCS (3.0 or 10.0 mg/kg, ip) significantly attenuated SCOP induced deficits in the MWM as measured by latency to find the submerged platform. For comparison, the long-acting acetylcholinesterase inhibitor galanthamine (GAL) was tested in the T-maze (1.25, 2.5, or 5.0 mg/kg, ip) and the MWM (2.5 or 5.0 mg/kg, ip). GAL attenuated SCOP-induced deficits in both learning and memory models similar to DCS. These data suggest that the strychnine insensitive partial glycine agonist, D-cycloserine, may be efficacious in disease states of central cholinergic hypofunction such as Alzheimer's disease. PMID- 8476383 TI - The depth profile of electrically induced tectal sustained potential shift responses in the goldfish (Carassius auratus). AB - Tectal sustained potential shifts (SPSs) were recorded in response to electrical stimulation of the tectal surface in immobilized goldfish using saline-filled glass microelectrodes. The peak amplitudes of surface recorded SPS responses were negative, this negativity declining with increasing tectal depth, reversing in polarity at a depth of ca. 350 microns and subsequently increasing in positivity. These opposing SPS polarities are attributed to field potentials generated by the source and sink of extracellular K+ ([K+]e) redistribution through a functional syncitium of radially connected glia. PMID- 8476384 TI - Effect of the tail ganglion on swimming activity in the leech. AB - In the medicinal leech, Hirudo medicinalis, isolated segmental nerve cords are capable of generating swimming activity. The role played by the head and tail ganglia in regulating the expression of swimming activity by the segmental nerve cord was evaluated by comparing swimming activity in nerve cord preparations with and without the head and tail ganglia attached. Several swim properties were examined, including length of induced swim episodes, ability to initiate swim episodes, swim cycle period, and phase. We found that, in general, the presence of the tail ganglion attached to isolated nerve cords countered the effects produced by the head ganglion on swimming activity. Moreover, we observed that the tail ganglion itself provides excitatory drive to the swim generating system. Thus, the inputs from the head and tail ganglia influence significantly the expression of swimming activity. PMID- 8476385 TI - A role for hippocampus in the utilization of hunger signals. AB - The hippocampus is generally regarded as an important anatomical substrate for learning and memory (e.g., Eichenbaum, Otto, & Cohen, Behavioral and Neural Biology, 57, 2-36, 1992; Squire, Psychological Review, 99, 195-231, 1992). In the present research, we provide evidence that the hippocampus is also involved with another function--utilization of hunger state signals. Rats with selective ibotenate lesions of the hippocampus were found to be impaired in their ability to discriminate between the interoceptive sensory consequences of food deprivation and satiation. At the same time the ability of these rats to discriminate between different exteroceptive cues was unaffected. These results suggest that deficits in discriminative performance were specific to interoceptive state stimuli. In addition, hippocampal-damaged rats also seemed unable to use their food deprivation stimuli as signals to engage in normal feeding behavior. Our results argue that although the hippocampus may be important for learning and memory processes, it also deserves consideration as a neural substrate for the regulation of food intake and perhaps other functions which involve interoceptive signals. PMID- 8476386 TI - Memory expression is blocked by the infusion of CNQX into the hippocampus and/or the amygdala up to 20 days after training. AB - Bilateral infusion of CNQX (0.5 microgram) into the amygdala and the dorsal hippocampus prior to a retention test blocked the expression of step-down inhibitory avoidance in rats 6, 13, or 20 days after training. Retention test performance recovered 90 min after the infusions. Pretest intrahippocampal CNQX (0.5 microgram) blocked the expression of habituation to a novel environment measured 20 days after training. The data suggest that memory expression depends on non-NMDA receptor-mediated mechanisms, perhaps the expression of LTP, up to at least 20 days after acquisition. These mechanisms operate in the hippocampus in both tasks and in the amygdala in the avoidance task. PMID- 8476387 TI - Chronic administration of alcohol in the developing rat: expression of functional tolerance and alcohol olfactory aversions. AB - Three experiments were designed to evaluate the acquisition and expression of tolerance to ethanol in preweanling rats. Administrations were begun on Postnatal Day 13 (PD13) and continued, on alternating days, through PD23. Following either three or five administrations of a 2.5 g/kg dose of ethanol, animals expressed tolerance to the motor-impairing consequences of acute ethanol, as measured through attenuated latencies to perform a righting reflex. However, no tolerance was evident when it was assessed through the hypothermic response to ethanol delivery (Experiment 1). The results of subsequent experiments suggested that this tolerance was not due to lower levels of ethanol in the blood and brain of the chronically exposed subjects (Experiment 2) nor to the development of behavioral tolerance, such as learning to perform the motor task in the presence of intoxication (Experiment 3). Additional tests determined that tolerance level did not alter the infant rats' ability to learn about the orosensory cues associated with ethanol delivery. Specifically, tests confirmed previous studies that an aversion to ethanol odor was formed as a result of the chronic administration procedure, presumably due to the animals associating the orosensory properties of eliminated ethanol during intoxication with the aversive consequences of this state. These results provide evidence that tolerance can develop in the preweanling rat, and that at least one measure (righting reflex) can be used to assess its development early in life. PMID- 8476388 TI - A test of the equal-environment assumption in twin studies of psychiatric illness. AB - The traditional twin method is predicated on the equal-environment assumption (EEA)--that monozygotic (MZ) and dizygotic (DZ) twins are equally correlated in their exposure to environmental events of etiologic importance for the trait under study. In 1968, Scarr proposed a test of the EEA which examines the impact of phenotypic similarity in twins of perceived versus true zygosity. We apply this test for the EEA to five common psychiatric disorders (major depression, generalized anxiety disorder, phobia, bulimia, and alcoholism), as assessed by personal interview, in 1030 female-female twin pairs from the Virginia Twin Registry with known zygosity. We use a newly developed model-fitting approach which treats perceived zygosity as a form of specified familial environment. In 158 of the 1030 pairs (15.3%), one or both twins disagreed with the project assigned zygosity. Model fitting provided no evidence for a significant influence of perceived zygosity on twin resemblance for any of the five disorders. Although limited in power, these results support the validity of the EEA in twin studies of psychiatric disorders. PMID- 8476389 TI - Testing hypotheses about direction of causation using cross-sectional family data. AB - We review the conditions under which cross-sectional family data (e.g., data on twin pairs or adoptees and their adoptive and biological relatives) are informative about direction of causation. When two correlated traits have rather different modes of inheritance (e.g., family resemblance is determined largely by family background for one trait and by genetic factors for the other trait), cross-sectional family data will allow tests of strong unidirectional causal hypotheses (A and B are correlated "because of the causal influence of A on B" versus "because of the causal influence of B on A") and, under some conditions, also of the hypothesis of reciprocal causation. Possible sources of errors of inference are considered. Power analyses are reported which suggest that multiple indicator variables will be needed to ensure adequate power of rejecting false models in the presence of realistic levels of measurement error. These methods may prove useful in cases where conventional methods to establish causality, by intervention, by prospective study, or by measurement of instrumental variables, are unfeasible economically, ethically or practically. PMID- 8476390 TI - Analyzing twin resemblance in multisymptom data: genetic applications of a latent class model for symptoms of conduct disorder in juvenile boys. AB - A model based on the latent class model is developed for the effects of genes and environment on multivariate categorical data in twins. The model captures many essential features of dimensional and categorical conceptions of complex behavioral phenotypes and can include, as special cases, a variety of major locus models including those that allow for etiological heterogeneity, differential sensitivity of latent classes to measured covariates, and genotype x environment interaction (G x E). Many features of the model are illustrated by an application to ratings on eight items relating to conduct disorder selected from the Rutter Parent Questionnaire (RPQ). Mothers rated their 8- to 16-year-old male twin offspring [174 monozygotic (MZ) and 164 dizygotic (DZ) pairs]. The impact of age on the frequency of reported symptoms was relatively slight. Preliminary latent class analysis suggests that four classes are required to explain the reported behavioral profiles of the individual twins. A more detailed analysis of the pairwise response profiles reveals a significant association between twins for membership of latent classes and that the association is greater in MZ than DZ twins, suggesting that genetic factors played a significant role in class membership. Further analysis shows that the frequencies of MZ pairs discordant for membership of some latent classes are close to zero, while others are definitely not zero. One possible explanation of this finding is that the items reflect underlying etiological heterogeneity, with some response profiles reflecting genetic categories and others revealing a latent environmental risk factor. We explore two "four-class" models for etiological heterogeneity which make different assumptions about the way in which genes and environment interact to produce complex disease phenotypes. The first model allows for genetic heterogeneity that is expressed only in individuals exposed to a high-risk ("predisposing") environment. The second model allows the environment to differentiate two forms of the disorder in individuals of high genetic risk. The first model fits better than the second, but neither fits as well as the general model for four latent classes associated in twins. The results suggest that a single-locus/two-allele model cannot fit the data on these eight items even when we allow for etiological heterogeneity. The pattern of endorsement probabilities associated with each of the four classes precludes a simple "unidimensional" model for the latent process underlying variation in symptom profile in this population. The extension of the approach to larger pedigrees and to linkage analysis is briefly considered. PMID- 8476391 TI - Factors modulating preferences of female house mice for males differing in t complex genotype: role of t-complex genotype, genetic background, and estrous condition of females. AB - The present study investigates factors mediating odor and social preferences in female house mice (Muc domesticus) based on the t-complex genotype of males. Previous studies in this laboratory showed that females prefer the odors of wild type (+/+) males over those that carry lethal genes (+/t). The purpose of this study was to determine the genetic, hormonal, and environmental factors that regulate these preferences. The variables examined include t-complex genotype, genetic background, estrous condition of test females (+/+ or +/t), and genotype of the test female's parents. Results indicate that female preferences for +/+ males are dependent upon the t-complex genotype and estrous condition of test females. Only +/t females in estrus showed preferences for +/+ males. Estrous cycle condition effects were seen in both wild (+/+w5) and inbred (129 +/tw5)females. Homozygous females (+/+) and diestrous females of both genotypes did not demonstrate preferences for either +/+ or +/t males. PMID- 8476392 TI - Bi- and multivariate analyses of diallel crosses: a tool for the genetic dissection of neurobehavioral phenotypes. AB - The genetic-correlational approach provides a very powerful tool for the analysis of causal relationships between phenotypes. It appears to be particularly appropriate for investigating the functional organization of behavior and/or causal relationships between brain and behavior. A method for the bivariate analysis of diallel crosses that permits the estimation of correlations due to environmental effects, additive-genetic effects, and/or dominance deviations is described, together with a worked-out example stemming from a five times replicated 4 x 4 diallel cross between inbred mouse strains. The phenotypes chosen to illustrate the analysis were locomotor activity and rearing frequency in an open field. Large, positive additive-genetic and dominance correlations between these two phenotypes were obtained. This finding was replicated in another, independently executed, diallel cross. PMID- 8476393 TI - A maximum-likelihood model-fitting approach to conducting a Hayman analysis of diallel tables with complete or missing data. AB - A method is presented for conducting a Hayman analysis of non-replicated diallel tables using a maximum-likelihood (ML) model-fitting approach, rather than a traditional analysis of variance (ANOVA) approach. Hayman's linear model for a diallel analysis is used to generate a table of expected cell means. This table of expected cell means is fit to a table of observed cell means, and the fit is assessed using a chi-square value. Often data collected from diallel crosses fail to meet the underlying assumptions of ANOVA. The ML method makes no assumptions about equal cell sizes or homogeneity of variance. Thus, the ML method for diallel analysis provides some statistical advantages over ANOVA methods. The ML method also offers the advantage of having the ability to analyze diallels with missing cells. Using the ML method, incomplete diallel tables can be analyzed, and the partitioning of all the sources of variation in a diallel table is still accomplished from the remaining crosses. These advantages make the ML method an attractive approach for extracting the maximum amount of information from a diallel table. PMID- 8476394 TI - Bidirectional selection for female receptivity in Drosophila melanogaster. AB - A wild population of Drosophila melanogaster was subjected to selection for high and low female receptivity. Selection was only applied in females on the basis of the mating times observed in a 30-min period. We applied a selection paradigm that allowed us to conclude that females unmated after 30 min correspond to the truncated upper tail of the distribution underlying mating times. Selection was successful, with mean mating times of about 5 min for the high lines, 35 min for the low lines, and 12 min for the control. Receptivity of the selection lines remained steady after 42 generations of relaxed selection, suggesting a lack of natural selection on receptivity in laboratory conditions. We also found a clear relationship between high or low receptivity and high or low frequency of hybridization with D. simulans males, emphasizing the role of female receptivity in maintaining isolation with its sibling species D. simulans. PMID- 8476395 TI - Female song preference and the period gene in Drosophila. AB - Mutations at the period (per) locus in Drosophila melanogaster alter rhythmic components of the male courtship song. We have examined the mating speed of females homozygous for mutant per alleles when presented with artificial mutant songs. Mutant females retain a preference for wild-type over mutant songs, thus male song and female preference are probably under separate genetic control. In contrast, per-mutant females from an established laboratory stock which had been maintained for nearly two decades appear to have an enhanced response to the corresponding mutant song in that they no longer discriminate against mutant song. These results are discussed in terms of the "genetic coupling" and "coevolution" theories of complementarity between male and female components of communication system. PMID- 8476396 TI - Identification of stimuli that mediate experience-dependent modification of homosexual courtship in Drosophila melanogaster. AB - A naive, sexually mature D. melanogaster male tested with a young, sexually immature male will perform vigorous courtship, but the mature male will perform much less courtship if he is subsequently tested with a second young male. This phenomenon is called experience-dependent courtship modification (EDCM). We have shown that exposure to either or both of the two courtship-stimulating pheromones that immature males synthesize is sufficient to induce EDCM. PMID- 8476397 TI - The effect of anesthesia on the photoresponses of four sympatric species of Drosophila. AB - Five isofemale strains from each of four sympatric species, Drosophila immigrans, D. repleta, D. melanogaster, and D. affinis, were lightly anesthetized with ether, CO2, Flynap, or cold temperature. The photoresponse of each treatment group was measured in an open field and a Y-tube apparatus. Relative light values were compared with those of the unanesthetized control groups of each species, as well as among the different treatments themselves and among species. Significant differences between species were apparent for all treatments in the Y-tube and for all treatments except ether and CO2 in the open field. Response to anesthesia may differ between species due, in part, to their differing genotypes. Comparing treatment groups within species in the Y-tube design, all species except D. melanogaster showed significant differences between treatments. In the open field, only D. affinis was significantly affected. Particularly in the Y-tube, anesthetized flies generally differed significantly from the controls, indicating that the use of anesthesia during a behavioral study could cause deviations in behavior from that of normal unanesthetized flies. PMID- 8476398 TI - Putting the family back in the child. AB - As clinicians and scientists we see daily the close tie between parental competence and emotional functioning and how children succeed with many of life's stressors. Inadequate attention has been paid to the theoretical underpinnings of predicting children's emotional reactions to stress from a systems perspective. Longitudinal developmental studies of parental influence on children's ability to cope with life's frustrations, through reciprocal interactions and genetic predispositions, are mandatory. Theoretical frameworks are already developed which must be drawn on to derive the best predictions of when and how to involve our child patients with family support. The current essay will attempt to bridge family systems and social network theories to the understanding of children's coping with medical stressors. PMID- 8476399 TI - Reality monitoring in obsessive-compulsive disorder. AB - Individuals with obsessive-compulsive disorder (OCD) often doubt whether they have performed an action or merely imagined having performed it. Such doubts suggest that OCD patients may have deficits in reality monitoring--the ability to distinguish memories of doing from memories of imagined doing. We compared the reality monitoring abilities of OCD checkers, OCD noncheckers and normal control Ss. Although we found no evidence of reality monitoring deficits in OCD patients, they tended to express less confidence in their memories relative to control Ss. These findings suggest that obsessional doubt may reflect deficits in memory confidence rather than deficits in memory per se. PMID- 8476400 TI - Cognitive processes in social phobia. AB - Social phobics, anxious controls and non-patient controls took part in a brief videotaped conversation with a stooge in order to investigate the cognitive model of social phobia. Thoughts, behaviour, and attention during the conversation were assessed. Compared to the control groups, social phobics had more negative self evaluative thoughts, performed less well, and systematically underestimated their performance. There were no differences in attention between the three groups. Content analysis of thought sampling data from the conversation, and from three hypothetical situations, revealed that few of the negative thoughts reported by social phobics explicitly mentioned evaluation by other people. This suggests that social phobics may not closely monitor other people's responses in social situations and hence that their thoughts are not data driven. The results are discussed in relation to the cognitive model of social phobia and suggestions are made for improvements in the treatment of social phobia. PMID- 8476401 TI - Somatic symptoms and panic attacks: a retrospective study of learning experiences. AB - Individuals with panic attacks evaluate physical anxiety symptoms as dangerous and tend to respond to them with fear. In a retrospective questionnaire study, we explored childhood and adolescent learning experiences with respect to somatic symptoms of panickers. Compared to normal controls (N = 61), patients with panic disorder (N = 121), infrequent panickers (N = 86) and patients with other anxiety disorders (N = 38) reported more frequent instances prior to age 18 when they had experienced symptoms like dizziness, shortness of breath, palpitations or nausea, accompanied by special attention from their parents and instructions to restrain from strenuous or social activities. The differences were due to higher symptom frequencies in the anxiety groups. All anxiety groups reported more frequent uncontrolled behavior of their parents than controls. Patients with panic disorder and infrequent panickers reported that their parents had suffered more frequently from physical symptoms typical of anxiety than patients with other anxiety disorders or normal controls. Panickers, but not patients with other anxiety disorders, had observed sick-role behavior related to panic symptoms in their parents more often than controls. Panic attack Ss reported a higher number of household members suffering from chronic illnesses than controls and patients with other anxiety disorders. No group differences were found in the reported behavior of parents when Ss had colds. Overall, the results point to the role of severe illnesses and physical symptoms typical of anxiety in significant others in the history of Ss with panic attacks. These experiences during childhood and adolescence may contribute to their belief that physical symptoms are dangerous. In contrast, there was no specificity for panic with respect to the Ss' own physical symptoms or cold-related symptoms. PMID- 8476402 TI - Group cognitive-behavioral treatment of panic disorder. AB - The present study examined the efficacy of an 8-wk, cognitive-behavioral group treatment for panic disorder. Patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia were randomly assigned to treatment (N = 34) or delayed treatment control (N = 33). The treatment consisted of: (a) education and corrective information; (b) cognitive therapy; (c) training in diaphragmatic breathing; and (d) interoceptive exposure. At posttreatment, 85% of treated Ss were panic free, compared to 30% of controls. Treated Ss also showed clinically significant improvement on indices of anxiety, agoraphobia, depression and fear of fear. Recovery, as estimated conservatively by the attainment of normal levels of functioning on each of the major clinical dimensions of the disorder (i.e. panic, anxiety and avoidance), was achieved in 64% of the treated Ss and 9% of the controls. At the 6 month follow-up, 63% of the treated patients met criteria for recovery. These findings mirror those from recently-completed trials of individually-administered cognitive-behavioral treatment, and suggest that CBT is a viable alternative to pharmacotherapy in the treatment of panic disorder. PMID- 8476403 TI - Helpless behavior. AB - In the present research, we investigated helpless behavior and the responses it elicits from others. Study One used the act-frequency approach to develop a self report measure of prototypically helpless behaviors. In a sample of college students (n = 75), this measure was validated against ratings by others. Many of the prototypically helpless behaviors we identified were interpersonal in nature, implying that they entail dependency and perhaps manipulativeness. In Study Two, we asked young adult (n = 249) Ss how they responded to people who showed varying amounts of helplessness. The most frequent response was trying to help the helpless individual feel better. As the frequency of helpless behavior increased, people were less likely to try to make him or her feel better, less likely to go along with the helpless individual, more likely to become angry and more likely to ignore or avoid this individual. Implications of these results for applications of the learned helplessness model were discussed, in particular the need to be cautious in assuming that all instances of observed passivity are good examples of learned helplessness. PMID- 8476404 TI - Psychological aspects of irritable bowel syndrome: comparisons with inflammatory bowel disease and nonpatient controls. AB - Patients with irritable bowel syndrome (IBS) (n = 121) were compared to 46 patients with inflammatory bowel disease (IBD), and to 45 nonpatient controls on a variety of psychological tests and on symptomatology. The most consistent finding was the ordering of group psychological test means such that, on 11 of 14 measures, IBS patients scored higher than IBD patients, who in turn scored higher than the nonpatient controls. The two patient groups differed significantly only on measures of anxiety with the IBS patients scoring significantly higher on all three measures. IBS patients also reported significantly more severity of abdominal pain than the IBD patients; while IBD patients reported more episodes of diarrhea, they did not rate them as significantly more severe than did the IBS patients. Various other parameters of the IBS population are also explored and implications for treatment and future study are discussed. PMID- 8476405 TI - The revised Stroop color-naming task in social phobics. AB - Information processing was examined in a sample of social phobic individuals using a revised version of the Stroop color-naming task. In the first of two experiments, the response latencies of social phobics and matched community controls were compared when color-naming socially threatening words, physically threatening words and color words. Social phobics demonstrated greater response latencies regardless of type of stimulus word and additional interference in color-naming social threat words compared to the control group. The second experiment examined the cognitive structural change that has been hypothesized to accompany successful treatment of individuals with an anxiety disorder. Social phobics who were treated with cognitive-behavioral group therapy, phenelzine or pill placebo were classified as treatment responders or nonresponders, and their latencies to color-naming on the Stroop task were compared. Treatment responders showed a significant reduction in latencies to color-name social threat words (vs matched control words) while nonresponders did not. This effect was not demonstrated with color words or physically threatening words. Clinical implications and future research directions are discussed. PMID- 8476406 TI - Identification of trichotillomania cue profiles. AB - To explore the usefulness of emotional and environmental cues in distinguishing different patterns and potential subtypes of hair pulling in trichotillomania, we looked at the responses of 75 chronic hair pullers who had identified relevant cues for hair pulling from a 339 item list. Principal components analysis suggested two independent components which were important to hair pulling, one distinguished by negative affective states (NA), and the other by sedentary activities and contemplative attitudes (S). High NA scores were related to hair pulling which was the focus of the Ss' attention, as well as with increased prevalence of lifetime obsessive compulsive disorder, other anxiety disorders, current and past depression, and obsessive compulsive personality disorder. High SA scores were related to a history of major depression only. Weighted scores on these components may be useful in further elaborating the phenomenology of trichotillomania and designing appropriate treatment interventions. PMID- 8476407 TI - The role of worrisome thinking in the suppression of cardiovascular response to phobic imagery. AB - Speech-fearful subjects repeatedly imagined a phobic image while heart rate and subjective reports of fear were monitored. Subject groups differed according to the type of mental activity that preceded each image. One group thought about a relaxing situation (Relaxation) and one group engaged in worrisome thinking (General-Worry). Three other groups were pre-trained to worry during their pre image mentation periods with an emphasis on: (a) the thoughts; (b) the images; or (c) the affect experienced during worry. Cardiovascular effects occurred only on the first image presentation. Thought-Worry produced significantly less heart rate response than did Relaxation; the other worry conditions fell nonsignificantly between these two groups. Within-group correlations between heart rate response to the image and the reported predominance of thought relative to imagery during the preceding mentation period showed that: (a) greater worrisome thinking in General-Worry was related to less cardiovascular response; and (b) greater relaxed thinking in Relaxation was associated with greater cardiovascular response. These results support the hypothesis that it is the worrisome thinking aspect of worry that may inhibit the emotional processing of phobic material and that Gray's mismatch theory of anxiety elicitation may account for these effects. PMID- 8476408 TI - Outcome profiles in the treatment of unipolar depression. AB - Treatment efficacy is typically evaluated by examining group means and pre-post change scores. Although informative, such analyses may obscure individual or subgroup differences in response (outcome profiles). The present study used two different methods to define treatment outcome profiles--rationally-derived criteria (Frank et al., Archives of General Psychiatry 48, 851-855, 1991) and dynamic clustering--to evaluate four treatments of unipolar depression: behaviour therapy, amitriptyline, psychodynamic psychotherapy and relaxation training (attention placebo). The profiling methods yielded similar results. Regardless of treatment, the majority of patients displayed either a recovery or nonremission outcome profile, with relatively few instances of remission followed by a recurrence of depression. These findings challenge the view that any of the treatments are associated with a strong tendency to relapse, at least over the 3 month follow-up period. To further characterize the major outcome profiles, discriminant analysis was performed. Results indicated that recovery and nonremission profiles differed in that the latter was associated with a longer and more severe index episode and greater neuroticism. A number of variables, including family history of depression and therapists' prediction of outcome, failed to distinguish recovered from unremitted patients. PMID- 8476409 TI - Assessing reliable and clinically significant change in social phobia: validity of the social phobia and anxiety inventory. AB - The ability of the Social Phobia and Anxiety Inventory (SPAI) to measure change as a function of treatment for social phobia was assessed. In addition to determining treatment sensitivity of the SPAI, changes over the course of treatment were examined to determine if they were reliable and clinically significant. The results indicated that although a number of measures showed statistically significant change, only on the SPAI was that change reliable and clinically significant. The use of outcome measures that are reliable and clinically significant for social phobia as well as other disorders is discussed. PMID- 8476410 TI - Two novel tachykinin-related neuropeptides in the echiuroid worm, Urechis unicinctus. AB - Two novel neuropeptides, urechistachykinin I (H-Leu-Arg-Gln-Ser-Gln-Phe-Val-Gly Ser-Arg-NH2) and urechistachykinin II (H-Ala-Ala-Gly-Met-Gly-Phe-Phe-Gly-Ala-Arg NH2), were isolated from the ventral nerve cords of the echiuroid worm, Urechis unicinctus. These peptides showed a contractile action on the inner circular body wall muscle of the animal. Their amino acid sequences were found to be significantly homologous with those of the vertebrate and insect tachykinins. The urechistachykinins potentiated spontaneous rhythmic contractions of the cockroach hindgut. PMID- 8476411 TI - Heterologous expression of the serotonin 5-HT1A receptor in neural and non-neural cell lines. AB - Stable expression of neuronal receptors in cell lines of neural origin is important for studies of neurotransmitter mediated signal transduction. We have achieved this for the first time in three cell lines which are derived from various tissues of neural origin (hippocampus, HN2; chinese hamster brain explant, NCB-20; rat dorsal root ganglion, F-11). Following electroporation assisted transfer of a construct containing the hippocampal serotonin 5-HT1A receptor (5-HT1AR) DNA, one neural cell line, NG-108-15 (murine neuroblastoma x C6 glioma), failed to express the transfected activity, while three others as well as the non-neural CHO (chinese hamster ovary) cells expressed high levels of the receptor. Upon normalization to coexpressed human beta-hexosaminidase B activity, it was found that the human 5-HT1AR, which is normally concentrated in the hippocampus and at a lesser density in the brain, was expressed at the highest level (15.7 x 10(4) receptors/cell) in the HN2 followed by the NCB-20 (8.3 x 10(4) receptors/cell), F-11 (4.4 x 10(4) receptors/cell) and lastly the non-neuronal CHO (4.2 x 10(4) receptors/cell) cells. Ten-twelve days after passage, a striking increase in expression of the receptor was observed only in the cell lines of neural origin. By contrast, there was no appreciable increase in expression of the transfected 5-HT1AR in the non-neural CHO cells over time. This late increase in expression was eliminated in cells which had been maintained in low glucose (1 g/L) for the first two days after passage, thus establishing a vital role of glucose in expression of the transfected 5-HT1AR in cell lines of neural origin. In all cases the 5-HT1AR was negatively coupled to adenylate cyclase, as evidenced by an agonist mediated decrease in prostaglandin E1 stimulated cyclic AMP levels. PMID- 8476412 TI - Transactivation of cellular promoters by an integrated hepatitis B virus DNA. AB - A new Hepatitis B virus(HBV) DNA integrant clone DA2-6, isolated from a human hepatocellular carcinoma(HCC) genomic library, was tested for its ability to transactivate expression of other genes. DA2-6 consists of 3.7 kb flanking cellular sequences and an integrated 2.8 kb HBV DNA which covers the region of preS, S, and the 3' truncated X. Using a chloramphenicol acetyltransferase (CAT) assay, a number of cellular and viral promoters were transactivated by DA2-6, and the spectrum of transactivational effect was the same as that by the wild type X gene of the virus. Deletion mutant analyses indicated that the transactivation function of DA2-6 is expressed by the region that encodes a truncated X-cell fusion product. PMID- 8476413 TI - Onset of new catalytic activity in immobilized spores of Aspergillus ochraceus TS due to in situ germination: C17-C20 lysis accompanies 11 alpha-hydroxylation of steroid. AB - The change in product pattern during transformation of progesterone by calcium alginate entrapped spores of Aspergillus ochraceus TS (A. ochraceus TS) due to germination in situ is reported. While progesterone was transformed exclusively to its 11 alpha-hydroxy derivative by both free and immobilized spores of A. ochraceus TS, the latter germinated in situ by yeast extract furnished 11 alpha hydroxyprogesterone and C19 steroids during transformation under identical conditions. The characterization of metabolite(s) and the pathway proposed demonstrated that delta 1-dehydrogenation and lysis of C17-C20 bond are apparently two independent reactions. The change in product profile due to activation of immobilized spores is believed to be caused by accumulation of compatible solutes in the biocatalyst which had relatively low water content. PMID- 8476414 TI - The mitochondrial DNA mutation at 8993 associated with NARP slows the rate of ATP synthesis in isolated lymphoblast mitochondria. AB - Mitochondria were prepared from three lymphoblast cell lines from patients with high percentage copy numbers of the human mtDNA 8993 mutation and compared to those prepared from related and non-related control cell lines. Rates of ATP synthesis with pyruvate/malate, succinate/rotenone, ascorbate/N'N'N'N' tetramethyl phenylene diamine were reduced to 67%, 58% and 54% of the control rates, respectively. The backward reaction measured as oligomycin sensitive ATPase was reduced to an average of 42% of that in controls. This mutation which changes a conserved leucine to an arginine in the putative membrane proton channel of mitochondrial ATPase effectively reduces the overall rate of oxidative phosphorylation. PMID- 8476415 TI - Biochemical characterisation of the isolated Anc2 adenine nucleotide carrier from Saccharomyces cerevisiae mitochondria. AB - The yeast mitochondrial adenine nucleotide carrier isoform encoded by the ANC2 gene has been specifically expressed in a yeast strain disrupted for the two other genes, ANC1 and ANC3. Isolation of the carrier in a functional form was achieved by utilisation of a mixture of two detergents, dodecylmaltoside and Emulphogen. The intrinsic fluorescence of the Anc2 protein was specifically and rapidly enhanced upon addition of the transportable nucleotides ADP and ATP. Fluorescence enhancement was prevented or reversed by the addition of a stoichiometric amount of CATR. Addition of CATR alone elicited a dose-dependent decrease of fluorescence. The ANC2-specific yeast stain offers the means to study a single ADP/ATP carrier, with a well-defined amino acid sequence, suitable for analysis of substrate- or inhibitor-induced conformational changes. PMID- 8476416 TI - Enhancement of the stability and activity of aspartase by random and site directed mutagenesis. AB - Enzymatic generation of mutant libraries for random mutagenesis of aspartase gene from E. coli J2 was made. A mutant enzyme with 4-fold increase in aspartase activity was found. It is stable at pH7.5-9.0 (wild-type: pH7.0-8.0); heat stability and alpha-helicity are higher than those of the wild-type. By using site directed mutagenesis, the aspartase was activated by replacement of Lys-126 with an arginine residue. The mutation produced functional alterations without appreciable structure changes. The optimum pH for the mutant enzyme is 8.5. The stable pH range is 7.0-9.0. Heat stability is higher than that of the wild-type one. Activity of the mutant enzyme is about 5-fold as much as that of wild-type one. PMID- 8476417 TI - Occurrence of prenylated proteins in plant cells. AB - In this paper evidence is presented for the occurrence of prenylated proteins in plants. When spinach leaves were incubated in the presence of [3H]mevalonate non extractable lipids were found in the protein fraction after extraction with organic solvents. Alkaline hydrolysis liberated phytol, polyprenyl phosphates-11 15 and also, in contrast to animal cells, polyprenols-11-15. Complete removal of farnesol and geranylgeraniol required the cleavage of thioether linkages by iodomethane. The results indicate that several polyisoprenoid lipids in plant cells are covalently bound to proteins. So far a protein fraction dominated by one or more proteins in the 23 kDa region has been identified. PMID- 8476418 TI - Interleukin 3 promotes histamine synthesis in hematopoietic progenitors by increasing histidine decarboxylase mRNA expression. AB - Interleukin 3 (IL-3) is a potent stimulator of histamine production by cells from murine hematopoietic organs. We demonstrate herein that this phenomenon results from increased histidine decarboxylase (HDC: EC 4.1.1.22) activity in progenitor enriched bone marrow cells (around 5% of the total bone marrow) isolated from the low density layers of a discontinuous Ficoll gradient. HDC levels are markedly enhanced after a 24 h incubation with IL-3 while a 4 h exposure results only in a slight activation. It results from increased expression of the mRNA coding for HDC, as assessed by Northern blot analysis after a 24 h incubation with IL-3. At the same time point and after a 4 h stimulation, we have evaluated the percentage of cells in this population which express HDC mRNA in response to IL-3, using in situ hybridization with the antisense riboprobe. We have thus established that enhanced HDC mRNA expression occurs in a small immature subset representing from 5 to 8% of the progenitor-enriched bone marrow cells. PMID- 8476420 TI - Prediction of structurally conserved regions of D-specific hydroxy acid dehydrogenases by multiple alignment with formate dehydrogenase. AB - We propose a multiple alignment of the sequence of formate dehydrogenase with the D-specific 2-hydroxy acid dehydrogenases family. Structurally conserved regions are predicted for those sequences corresponding to important regions of the catalytic and the coenzyme binding domains defined from the known three dimensional structure of the formate dehydrogenase, namely the nicotinamide binding site (beta D to beta F) and the beta A-loop-alpha B region containing the typical glycine pattern of the adenosine binding site, the catalytic histidine/aspartic acid pair and an arginine probably involved in the interaction with the carboxyl group of the substrate. PMID- 8476419 TI - In vivo delivery of human alpha 1-antitrypsin gene to mouse hepatocytes by liposomes. AB - The pTG7101 plasmid containing the full length human alpha 1-Antitrypsin was encapsulated in large (142 +/- 15 nm of diameter) and small (54 +/- 11 nm of diameter) liposomes and administered i.v. to mice (80 ng/mouse). Control animals were treated with empty (small and large) liposomes plus free DNA and with the liposome solvent buffer. The immunohistochemical results on liver cryosections and cytophotometric analysis of hepatocyte chromophore absorbance, after peroxidase reaction, indicated that significant presence of immunoreactive human alpha 1-antitrypsin was present 7 days after mice treatment with encapsulated DNA in small liposomes but not when large liposomes were used. This effect was observed in a great number of liver parenchymal cells. These results agree with the observation that only small liposomes have easy access to hepatocytes and support the idea that small liposomes are appropriate vehicles for in vivo delivery of specific genetic material to liver parenchymal cells, with high efficiency. PMID- 8476421 TI - Expression of soluble and insoluble fibronectin in rat aorta: effects of angiotensin II and endothelin-1. AB - This study has investigated the influence of the vasoconstrictor peptides angiotensin II (Ang II) and endothelin-1 (ET-1) on fibronectin expression by vascular smooth muscle cells (VSMC). In confluent, quiescent cultures of VSMC, Ang II and ET-1 elevated fibronectin mRNA levels in a time- and dose-dependent fashion. ET-1 and Ang II also induced a time-dependent expression of immunoreactive fibronectin in cultures of aortic organoids, and for both peptides the fibronectin immunoreactivity was most prominent within those medial smooth muscle cell layers close to the vessel lumen. Immunoprecipitation of biosynthetically labelled fibronectin elaborated by cultured VSMC revealed a predominant expression of soluble fibronectin in response to Ang II, whereas for ET-1 the newly synthesized fibronectin was predominantly incorporated into the extracellular matrix deposit of the cells. These findings indicate that Ang II and ET-1 may exert disparate effects on smooth muscle cell phenotype and migration. PMID- 8476422 TI - Photoacoustic detection of photosensitized oxygenations in highly absorbing samples. AB - A photoacoustic (PA) study of the relaxation processes of the excited states of photosensitizers in the presence of oxygen and chemical acceptors is described. It has been predicted theoretically that the ratio of PA amplitudes with and without acceptor depends on two parameters alpha and beta, related to the sensitizer and to the acceptor properties, respectively. Experimental studies were carried out on solutions of hematoporphyrin IX and methylene blue. The addition of an acceptor, specific to the singlet oxygen, like tetramethyl ethylene or furfuryl alcohol, appears to decrease significantly the photoacoustic signal amplitude within the band of absorption. PMID- 8476423 TI - A chicken embryo model to study the growth of human uveal melanoma. AB - In vitro cultured human uveal and skin melanoma cells were injected into the chicken embryonal eye at a stage when the immune system was not yet mature. The melanoma cells were accepted as part of the organism by the host. Even single melanoma cells could be traced by morphological methods as well as by immunohistochemical markers, such as S100, HMB-45, NKI/C3 and HNK-1. We found tumors in 20 and 40 percent of the embryos injected with uveal melanoma and skin melanoma, respectively. The embryos did not exhibit abnormal development of the eye as a result of the microinjection and had a high survival rate (90 and 60%, respectively) during embryogenesis. With this model for uveal melanoma the growth and possibly the metastatic behavior of human uveal melanoma cells can be studied. PMID- 8476424 TI - HuMig: a new human member of the chemokine family of cytokines. AB - Characterization of lymphokine-activated genes in mouse macrophages led to the identification previously of Mumig, an interferon-gamma-inducible murine gene that encodes a member of the chemokine family of cytokines. The Mumig cDNA probe was used to screen a cDNA library prepared from cultures of the THP-1 human monocytic cell line that had been treated with interferon-gamma. This led to the identification of Humig, a new human member of the chemokine gene family. Humig is induced in THP-1 cells and in peripheral blood mononuclear cells by interferon gamma but not by interferon-alpha or by lipopolysaccharide. Analysis of mouse and human genomic DNAs suggested that the Mumig and Humig genes are true mouse-human homologues. The Humig mRNA encodes a predicted secreted HuMig protein of 103 residues, M(r) 11,725. PMID- 8476425 TI - Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells. AB - Two novel tyrosine kinase cDNAs were obtained from murine mast cells. These kinases, Emb and Emt, constitute a novel tyrosine kinase subfamily which may also include Tec, a kinase preferentially expressed in liver, and Dsrc28, a fruit fly kinase. Both lack hydrophobic stretches characteristic of the transmembrane domains found in growth factor receptor tyrosine kinases and carboxyl-terminal, negative regulatory tyrosine residue found in Src family kinases. In addition to the Src homology region 2 (SH2) and SH3 domains characteristic of the Src family kinases and other signaling molecules, Emb and Emt share a similar amino-terminal domain comprised mainly of two repeat segments. The emb 2.7-kb transcript was expressed in mast cells, myeloid cells and B lymphocytes while the emt 4.6-kb mRNA in mast cells, myeloid cells and T lymphocytes. The evidence for in vitro tyrosine kinase activity of Emb and Emt proteins is also provided. PMID- 8476426 TI - Survival of cancer patients on therapy with coenzyme Q10. AB - Over ca. 25 years, assays in animal models established the hematopoietic activities of coenzyme Q's in rhesus monkeys, rabbits, poultry, and children having kwashiorkor. Surprisingly, a virus was found to cause a deficiency of CoQ9. Patients with AIDS showed a-"striking"-clinical response to therapy with CoQ10. The macrophage potentiating activity of CoQ10 was recorded by the carbon clearance method. CoQ10 significantly increased the levels of IgG in patients. Eight new case histories of cancer patients plus two reported cases support the statement that therapy of cancer patients with CoQ10, which has no significant side effect, has allowed survival on an exploratory basis for periods of 5-15 years. These results now justify systematic protocols. PMID- 8476427 TI - Midkine, a novel neurotrophic factor, is present in senile plaques of Alzheimer disease. AB - An affinity purified antibody specific for midkine (MK) stained senile plaques in the brain of Alzheimer disease (AD) patients. After formic acid treatment, plaque staining was dramatically enhanced, and almost all beta-amyloid protein (BAP) deposits were also immunoreactive for MK. MK-immunoreactivity was not observed in normal cellular components nor in other pathological lesions including tangles in AD brain. Control brain sections were not immunoreactive for MK. The presence of MK in AD brain but not in control brain was confirmed by Western blotting. MK appears to be involved in the pathological process leading to senile plaque formation. PMID- 8476428 TI - A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat. AB - Recent advances in molecular biology have allowed the study of the candidate genes for essential hypertension. To identify the genes responsible for basal blood pressure in the spontaneously hypertensive rat strain, the rat model of genetic hypertension, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 progeny obtained from SHR and Wistar-Kyoto rats, a reference normotensive strain. Our investigation revealed that a locus on the chromosome 4 cosegregates with the blood pressure in SHR, especially at neuropeptide Y locus. The degree of cosegregation with all values of blood pressure without sodium loading was moderate but consistent. We propose that neuropeptide Y locus on chromosome 4 is a new candidate for the hypertensive effect in original SHR. PMID- 8476429 TI - Absence of 2'-deoxy-GTP in adult brain tubulin. AB - Nerve growth factor can stimulate incorporation of 2'-deoxy-GTP into the non exchangeable nucleotide sites in tubulin and cytoskeletal microtubules of PC12 pheochromocytoma cells and embryonic chick dorsal root ganglion neurons [J. M. Angelastro and D. L. Purich (1992) J. Biol. Chem. 267, 25685-25689]. We replaced and hydrolyzed exchangeable-site GTP and GDP in adult bovine brain tubulin by incubation with the non-hydrolyzable nucleotide analogue 5'-guanylyl methylenediphosphonate and alkaline phosphatase, thereby allowing us to analyze the non-exchangeable guanine nucleotides for GTP and dGTP. HPLC analysis reveals no evidence of dGTP in adult tubulin, suggesting further that the appearance of dGTP in tubulin and microtubules may be a characteristic of recently dividing neurons in response to nerve growth factor. PMID- 8476430 TI - Tumor necrosis factor-alpha increased the integrin alpha 2 beta 1 expression and cell attachment to type I collagen in human dermal fibroblasts. AB - Cell adhesion molecules of human dermal fibroblasts play an important role in the processes of wound healing. The effects of tumor necrosis factor- alpha (TNF) on the expression of integrin beta 1 subfamily in human dermal fibroblasts were examined. TNF preferentially induced the expression of alpha 2 beta 1 integrins, receptors for collagen and laminin, in a time and dose dependent manner. Cell attachment to type I collagen increased by the treatment with TNF. However, cell attachment to fibronectin and laminin was not increased. This TNF-induced cell attachment could be reduced significantly by anti-integrin alpha 2 beta 1 antibody. Antibodies against receptors other than alpha 2 beta 1 integrin did not significantly reduce cell attachment. These data suggest that the increased attachment of human dermal fibroblasts to type I collagen appears to be mediated predominantly through the augmentation of integrin alpha 2 beta 1 expression by TNF. PMID- 8476431 TI - Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2. AB - To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl2. SBC-3/Bcl2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3, with relative resistance values of 3.4, 7.6 and 5.7, respectively. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and taxol between SBC-3 and SBC-3/Bcl2. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC, in a concentration-dependent manner. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl2. Treatment with CDDP resulted in the same degree of DNA fragmentation in SBC-3 and SBC-3/Bcl2. These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis. PMID- 8476432 TI - A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line. AB - The polymerase chain reaction (PCR) was used to detect several forms of adenylyl cyclase (AC's) expressed in human erythroleukemia (HEL) cells. Degenerate oligonucleotide primers were synthesized based on the conserved sequences in the C2a area of the AC's. HEL cells were found to contain mRNA for type III and type VI AC. In addition, a novel AC message was identified. The cloned sequence, excluding primer areas, represented 69 amino acids with most similarity to rat AC's II and IV. Northern analysis of RNA from HEL cells demonstrated a 6.7 kilobase message. RNase protection assays revealed that in HEL cells the novel AC mRNA was dominant compared to types III and VI. Human embryonic kidney cells (HEK293) were also used a source of mRNA to synthesize cDNA for PCR reactions. The HEK293 cells were found to contain message corresponding to type II, III, VI AC as well as the novel AC message. The novel AC message was also detected in human brain tissue and was most abundant in the caudate, cerebellum and hippocampus. The smallest amount of novel AC mRNA in the tested brain tissue was found in the cortex. The mRNA for the novel AC was relatively abundant in human liver. PMID- 8476433 TI - Molecular basis of impaired pyruvate kinase isozyme conversion in erythroid cells: a single amino acid substitution near the active site and decreased mRNA content of the R-type PK. AB - Conversion of pyruvate kinase (PK) isozymes from M2- to R-PK has been observed during erythroid cell maturation. To understand this mechanism, we analyzed the PK gene of a R-PK deficient patient, in whose erythrocytes the M2-PK was persistently expressed. A point mutation, 1102 GTC-->TTC was identified in the R PK cDNA, and it caused a single amino acid substitution from 368Val-->Phe. The residue is very close to the 372nd Gln, the putative binding site of the monovalent cation (K+). The impaired K+ binding would cause the decreased affinity for phosphoenolpyruvate, consequently the variant PK may be extremely unstable. Although the proband's other PK allele did not have any structural change, the R-PK mRNA level in reticulocytes was decreased. These findings suggested that both the structural mutation near the active site and the decreased mRNA level of the R-PK were responsible for the disorder. PMID- 8476434 TI - Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice. AB - Mice given one of several widely consumed cola drinks in place of drinking water for up to 8 weeks developed significant levels of covalent liver DNA adducts in a time dependent manner, as measured by 32P-postlabeling. These adducts were not detected in mice given tap water or one of 3 non-cola beverages. Adducts chromatographically identical to those induced by cola drinks were detected in mice treated with extracts of nutmeg or mace, spices from the nutmeg tree (Myristica fragrans Houttuyn), or with myristicin (1-allyl-5-methoxy-3,4 methylenedioxybenzene), the major spice constituent of nutmeg. In addition, small amounts of adducts derived from the hepatocarcinogen safrole (1-allyl-3,4 methylenedioxybenzene), a minor constituent of nutmeg, were observed. Liver DNA adducts were also detected in fetal liver when pregnant mice were intubated with myristicin. Possible implications of these findings for human health are discussed. PMID- 8476435 TI - Expression of the dystrophin gene in cultured fibroblasts. AB - The dystrophin whose defect is responsible for Duchenne and Becker muscular dystrophies is present in muscle, brain and cerebellum. We describe here the detection of dystrophin in human cultured skin fibroblasts, L809 cells and murine 3T6 cell line. Dystrophin transcripts initiated at the muscle specific first exon can also be amplified by cDNA-PCR from various fibroblastic cells. The expression of the dystrophin gene in fibroblasts could account for some abnormalities observed in patient's fibroblast cultures. PMID- 8476436 TI - A potent anti-metastatic activity of tumor invasion-inhibiting factor-2 and albumin conjugate. AB - Tumor invasion-inhibiting factor-2 (IIF-2) peptide was chemically conjugated to albumin with 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide hydrochloride. The molar ratio of the covalently linked IIF-2 peptide and albumin in the purified conjugate was 1.4 +/- 0.4, as determined with a radioactive peptide. The conjugate inhibited the invasion of HT1080 and B16FE7 cells in vitro at 40- to 60 fold lower concentrations than IIF-2 peptide. Scatchard analysis of binding data demonstrated that the IIF-2-albumin conjugate bound to HT1080 and B16FE7 cells with Kd values of 240 and 340 nM, respectively. The conjugate suppressed the lung colonization of B16FE7 cells more effectively than the IIF-2 peptide in an experimental metastasis. These results indicate that the covalent linkage of the IIF-2 peptide to a carrier macromolecule provides a structure that enables this peptide to exhibit increased inhibitory action in cancer cell invasion and metastasis, and that IIF-2 exerts its inhibitory action on invasion by binding to a specific binding site on the tumor cell surface. PMID- 8476437 TI - On the purity of 3X-recrystallized bovine alpha-chymotrypsin. AB - The results of an electrospray-mass spectrometric analytical study of aqueous solutions of fifteen commercial samples of 3X-recrystallized bovine alpha chymotrypsin are presented and discussed. It was found that only six samples were predominantly alpha-chymotrypsin and that two samples contained no alpha chymotrypsin at all. The remaining seven samples were found to be mixtures of alpha-chymotrypsin with other chymotrypsins and, in some cases, neochymotrypsinogens. The majority of the results are rationalised in terms of previously postulated and/or observed products of proteolytic activation of bovine chymotrypsinogen A. However, evidence is also presented for the presence in many of the samples of three new serine proteases, of significantly lower molecular masses than alpha-chymotrypsin, which cannot at present be explained. The paper is concluded with a brief discussion of the implications of the analytical findings for enzymological studies. PMID- 8476438 TI - Protective role of hemopexin on heme-dependent lung oxidative stress. AB - Tert-butyl hydroperoxide (t-BOOH)-dependent chemiluminescence of perfused rat lungs increased by almost 500% upon addition of heme (from 297 +/- 28% to 1204 +/ 125% of control, p < 0.01 vs no heme). Preincubation with hemopexin significantly decreased the heme-stimulated chemiluminescence to 779 +/- 155% of control (p < 0.01) When hemopexin was replaced with rat albumin heme-stimulated chemiluminescence decreased to 1007 +/- 104% (not significantly different from results with heme alone). In vitro studies showed that hemopexin did not decrease chemiluminescence from bovine serum albumin oxidation (493 +/- 94% compared to 292 +/- 81% of control in the absence of hemopexin) and that the heme-hemopexin mixture also emitted light when exposed to t-BOOH (264 +/- 66% of control). These results suggest that hemopexin specifically inhibits some of the oxidative reactions catalyzed by free heme and may have a protect tissue oxidation in conditions in which heme release occurs (i.e., stroke). PMID- 8476440 TI - Adverse reproductive outcomes and occupational exposures among nurses: an investigation of multiple hazardous exposures. AB - 1. The increasing numbers of pregnant women and women of childbearing age who are employed and exposed to hazardous substances pose occupational health concerns. 2. The findings of this study indicate the importance of not minimizing concern about exposure to radiation. Radiation monitoring should be implemented to a greater extent, and methods to measure low dose chronic radiation exposure should be developed. 3. Synergy between the adverse reproductive effects from multiple workplace factors among nurses, including but not limited to radiation, video display terminal use, and chemotherapeutic agents, warrants further evaluation. PMID- 8476441 TI - Implementing a university campus wellness model. AB - 1. Using a model to plan the development of a wellness program may enhance program success. The wellness model could be used as a basic framework to implement a health promotion program at any worksite. 2. The University Wellness model depicts an individual in control and riding toward wellness. The six dimensions in the model represent a holistic view of the individual. These dimensions consider the physical, occupational, spiritual, social, intellectual, and emotional aspects of the person to illustrate how these factors impact on the wellness concept. 3. This model may apply and be of significance to other workplace situations to increase worker productivity and decrease employer costs. PMID- 8476439 TI - A system for studying the effect(s) of familial Alzheimer disease mutations on the processing of the beta-amyloid peptide precursor. AB - Three different point mutations have been observed in some familial Alzheimer's disease pedigrees at a unique valine, Val717, near the carboxyl end of the beta Amyloid Peptide Precursor (beta APP). The effects of these mutations on the processing and cellular functions of beta APP can best be determined in the absence of the normal form(s) of the protein. We have used targeted mRNA degradation by a trans-acting hammerhead ribozyme to cleave and inactivate beta APP expression in vitro. The consensus ribozyme cleavage site, 5'GUC decreases X3, matches the Val717 nucleotide sequence in beta APP mRNA. Introduction of FAD point mutations which change Val717 decrease the rate of ribozyme cleavage by more than three orders of magnitude. Thus, ribozyme targeting of this site should allow the study of protein processing in vivo. Furthermore, a ribozyme targeted to mutant beta APP mRNA (Val717-->Ile) cleaved the mutant sequence 300-fold faster than the normal sequence. This suggests that ribozymes might lower mutant beta APP mRNA levels in FAD cells. PMID- 8476442 TI - Managing crises and trauma in the workplace: how to respond and intervene. AB - 1. Health care, human resource, and employee assistance provider professionals must be aware of the impact of trauma in the workplace. 2. Critical Incident Stress (CIS) refers to the work and situations that emergency service professionals face on a regular basis. Trauma in the workplace refers to a work setting, such as an industrial accident, personal injury/illness, or crime taking place in a work setting. The death or injury of an employee outside of the workplace is also considered traumatic for employees. 3. Victims of witnesses of a traumatic incident, a violent crime, physical maltreatment, or sexual abuse may experience Posttraumatic Stress Disorder (PTSD). Individuals of all ages are vulnerable to PTSD. 4. Unresolved CIS or a workplace trauma may result in PTSD for the involved individuals if not handled appropriately. PMID- 8476443 TI - Occupational health nursing in Finland. AB - Occupational health nursing in Finland is based on activities stated by the Occupational Health Care Act. Moreover, the occupational health nurse provides services that are based on agreements between the employer and the occupational health center. Occupational health nursing emphasizes preventive measures, such as the clarification of health hazards and job related risk factors, the arrangement of health examinations, health education, and organization of first aid. Occupational health nurses in Finland participate in continuing education at least every 5 years. In 1991 the option of specializing in Occupational Health as a part of the Masters of Health Care program became available at universities. PMID- 8476444 TI - OSHA's new standard: exposure to bloodborne pathogens. AB - Most health care workers in the U.S. are covered by OSHA's new standard on bloodborne pathogens exposure. Individual states that have their own occupational agency must enact a Standard that is at least as strict. Key elements of the Standard include an exposure control plan, universal precautions, engineering controls that stress sharps safety, personal protective equipment, exposure evaluation and follow up, and training. Employers are required to offer the hepatitis B vaccine free of charge to employees. Employees who decline the vaccine must sign a declination form. An OSHA inspection for compliance with this Standard will include review of records, a workplace walk through, and interviews with employees. OSHA has already cited and fined some workplaces for not complying with the Standard. PMID- 8476446 TI - Hiring practices and the occupational health nurse manager. PMID- 8476445 TI - Evaluating a federal health and fitness program: indicators of improving health. PMID- 8476447 TI - All nurses need to use research findings to guide their practice. PMID- 8476448 TI - Diagnosis and misdiagnosis of poisoning with the cyanide precursor acetonitrile: nail polish remover or nail glue remover? AB - Accurate diagnosis of acetonitrile ingestion is critical to management. Often this involves differentiating nail polish remover (acetone) from nail glue remover (acetonitrile). Initial symptoms of acetonitrile ingestion are indistinguishable from those of acetone and common alcohols. However, acetonitrile is metabolized to cyanide, producing severe delayed toxicity. Acetonitrile produced increased serum osmolality and osmolal gap, but these findings are non-specific and normal values cannot rule out potentially fatal exposure. Acetone, but not acetonitrile, was detectable in urine or serum with Acetest tablets; both were unreactive with a ketone dipstick. Acetone and acetonitrile could be detected with routine gas chromatography methods for alcohols. Both substances had identical retention times on the widely used stationary phase, 5% Carbowax 20M on graphitized carbon, and with GasChrom 254. Three other systems afforded unique retention times, but acetonitrile was easily mistaken for ethanol in two. Physicians and laboratories must take care to avoid misdiagnosis of acetonitrile ingestion as exposure to acetone, ethanol or another alcohol. PMID- 8476449 TI - Reliability of prehospital rating scales for case severity and status change. AB - The purpose of this report is to determine the reliability and sensibility of the currently available prehospital rating scales by a prospective evaluation of ambulance call reports using generalizability methodology. Sequential samples of emergency call data from the Hamilton Base Hospital Paramedic program database were used to sample calls randomly for a two-phase study. Phase I and II used blinded ambulance call report forms presented to six rates during three sessions in each phase. Generalizability (reliability) coefficients were then generated to determine the degree of reliability for the scales in both phases of the study. The generalizability coefficients for all scales are substantial or excellent using the standards commonly applied to agreement statistics. The conclusion of the study is that all ambulance officers can use the prehospital scales reliably. The reliability of these general measures is one of the parameters that will allow us to evaluate where basic and advanced prehospital care have an impact on overall patient outcome. PMID- 8476450 TI - Diagnostic and therapeutic utility of flumazenil in comatose patients with drug overdose. AB - From July 1, 1990 and June 30, 1991, 61 unconscious patients with drug intoxication were prospectively enrolled into this study in order to evaluate the efficacy and safety of flumazenil in the management of this patient population. Flumazenil was injected intravenously as a 0.3-mg bolus in the first minute followed by 0.2-mg and 0.3-mg doses every minute until a total dose of 1 mg was given or until the patient responded. The Glasgow coma scale and a sedation-level scoring system were checked prior to and at 1, 5, and 30 minutes after the dose eliciting response or on completion of the full dose of flumazenil. The patients were divided into two groups based on their response to flumazenil: group 1, responders (N = 55), and group 2, nonresponders (N = 6). Eleven patients from group 1 allowed us to retrieve drug information from these patients once mental status had recovered and patients were treated accordingly. In two cases endotracheal intubation and artificial ventilation were rendered unnecessary by the use of flumazenil. No undesirable hemodynamic effects were noted after flumazenil injection in this study, although none of the patients overdosed on antidepressants. Flumazenil may serve as a useful diagnostic and therapeutic tool in the management of selected cases of drug-induced coma. PMID- 8476451 TI - An evaluation of automated defibrillation and manual defibrillation by emergency medical technicians in a rural setting. AB - We show that automated external defibrillation training of emergency medical technicians (EMTs) is less time consuming than manual defibrillation training, and hypothesize that both improve survival from sudden cardiac death. Data on 91 cardiac arrests over 27 months among five basic life support services was collected before EMT-defibrillation (EMT-D) training. Subsequently, seven BLS services were trained in EMT-D using either manual difibrillation or automated external defibrillation technology, and 55 sudden cardiac death patients were entered after training. Manual defibrillation required 11 more hours per student in initial training. Survival to hospital discharge improved from two of 91 patients (2.2%) in the series before EMT-D training to nine of 55 patients (16.4%) after EMT-D training (P = .001). Improved survival was correlated with shorter prehospital defibrillation times, 8.84 minutes, when EMTs performed defibrillation versus 16.3 minutes before training when EMTs awaited advanced life support defibrillation (P < .001). To enhance equipment familiarity we allowed EMTs to apply three-lead electrode monitors to all medical/cardiac patients during transport (surveillance). There were six emergency medical service-witnessed "surveillance" arrests and three arrests survived to hospital discharge (50% survival). This group represented 33% of all survivors in the series. We recommend automated external defibrillation training for EMTs. Improved survival in sudden cardiac death cases in well-run emergency medical service systems should result from EMT-D training. Finally, we recommend that routine "surveillance" of high-risk patients during transport by defibrillation capable EMTs be considered in EMT-D programs, rather than limiting EMT-D only to units capable of rapid "man-down" response. PMID- 8476452 TI - The efficacy and safety of a continuous albuterol protocol for the treatment of acute adult asthma attacks. AB - We performed a prospective study over a 6-month period to test the efficacy and safety of a continuous nebulized albuterol protocol for the treatment of acute adult asthma attacks. All patients 18 years or older presenting to the emergency department with acute asthma attacks were begun by the triage nurse on the protocol of three continuous albuterol (2.5 mg) nebulizer treatments. Pretreatment and posttreatment peak flow, respiratory rate, pulse, and blood pressure were documented and patients gave a pretreatment and posttreatment rating of the clinical severity of their attack using a (1 to 10) visual analog scale. In addition, all adverse effects were noted. Seventy-six patients were entered in the study. The average age was 44 years (range, 20 to 82 years). Pretreatment and posttreatment peak flow, respiratory rate, pulse, blood pressure, and clinical severity were compared using the paired t test. Patients showed statistically significant increases in peak flow (128 to 292; P < .0001) and statistically significant decreases in respiratory rate (27 to 20; P < .0001); pulse, 103 to 94 (P < .0001); clinical severity, 7.8/10 to 1.8/10 (P < .0001); and blood pressure, 141/82 to 132/77 (P < .001). Adverse effects were minimal. Two patients (2.6%) felt flushed, three patients (4%) felt jittery, and one patient (1.3%) had a sensation of palpitations. We conclude that a continuous nebulized albuterol protocol is both extremely efficacious and safe for the treatment of acute adult asthma attacks. PMID- 8476453 TI - The effect of scrubbing and irrigation with normal saline, povidone iodine, and cefazolin on wound bacterial counts in a guinea pig model. AB - This study examines the effects of povidone iodine, normal saline, and cefazolin alone and after scrubbing on bacterial counts in contaminated animal lacerations. Twelve albino guinea pigs each received four lacerations inoculated with a standard inoculum of Staphylococcus aureus. Twelve hours after inoculation, each wound was biopsied to ensure contamination and then either treated or left as an untreated control. One wound on each animal was an untreated control. The remaining three lacerations on six pigs were irrigated with cefazolin (CZ) solution, normal saline, or 1% (wt/vol) povidone iodine solution (PI). Three lacerations on another six pigs were treated with 20% poloxamer 188 scrub (scrub) alone, scrub followed by PI irrigation (SCR/PI), or scrub followed by CZ irrigation (SCR/CZ). Quantitative bacteriology was performed on tissue biopsies 2 hours (time 1), 7 hours (time 2), and 12 hours (time 3) after irrigation. Posttreatment counts for PI, CZ, and normal saline irrigation were not different from control or one another (P > .05). Bacterial counts for SCR/PI were significantly lower than control (P < .05) for all posttreatment biopsies (1.8 to 2.9 mean log(10) decrease). SCR/CZ was significantly lower than control (P < .05) at times 2 and 3 only (1.7 to 2.0 mean log(10) decrease). In this guinea pig model, cleansing 12-hour-old lacerations contaminated with S aureus using SCR/PI or SCR/CZ significantly reduced bacterial counts over 12 hours. PMID- 8476455 TI - The influence of perceived risk of exposure to human immunodeficiency virus on medical students' planned specialty choices. AB - The purpose of this report is to determine the influence of the acquired immunodeficiency syndrome (AIDS) epidemic on medical students' training and career plans through a prospective, anonymous self-administered survey of 10 Likert-scaled (1 strongly agree to 5 strongly disagree) responses to statements assessing attitude toward patients with human immunodeficiency virus (HIV), adequacy of knowledge and experience with HIV, and influence of HIV on career choices. The study was done at a major AIDS referral university teaching hospital. The participants were first- through fourth-year medical students in spring 1990. A 72% (of 451 students) response revealed that both surgery and emergency medicine were perceived as high risk of exposure specialties. Students indicated an overall willingness to care for HIV-positive patients (mean, 2.54) and a general adequacy of knowledge and experience (mean 2.54). The AIDS epidemic has had little influence for training, future career, and practice locations (mean, 4.06). Responses differed by class year. The later class years were more willing to care for HIV patients (P < .001) and indicated more knowledge and experience with HIV (P < .001). Influence on career, training and practice location choices were without class trend. In contrast to some studies, this group of medical students had relatively positive attitudes toward patients with HIV and were not particularly influenced by the AIDS epidemic regarding career choices. PMID- 8476454 TI - Resuscitation decision making by New Mexico emergency medical technicians. AB - The extent to which Emergency Medical Service personnel are placed in situations in which difficult cardiopulmonary resuscitation decisions must be made has been poorly explored. Further, it is not known whether this kind of decision making is troubling to emergency medical technicians. Although it is likely that emergency medical service systems handle withholding cardiopulmonary resuscitation in a variety of ways, the authors chose to examine a cross-section of New Mexico emergency medical technicians. Using a survey instrument, emergency medical technicians of all training levels, representing several emergency medical service systems around the state were asked how many times in their career they had been in a situation in which cardiopulmonary resuscitation had been withheld without a direct physician order. Of 310 individuals surveyed, 211 (66.8%) responded that this had occurred at least once. When asked whether they had been troubled by one of these situations, 86 of 211 (41%) individuals responded "yes." When a variety of demographic factors were evaluated, only training to the paramedic level was identified as being an independent predictor of those who were troubled (P = .019). Emergency medical technician training, protocols, and do not resuscitate programs may need to be expanded to give further guidance to prehospital personnel when making difficult resuscitation decisions. PMID- 8476456 TI - Nasal septal abscess: an unusual complication of nasal trauma. AB - Injuries to the nasal septum may occur as a result of injuries to the nose. A case of nasal septal abscess, an unusual complication of nasal trauma, is presented. The pathophysiology, clinical course, and treatment of this disorder are discussed. This case demonstrates the need for careful evaluation of the nasal septum in all cases of nasal trauma. PMID- 8476457 TI - Retropharyngeal abscess in an afebrile child. AB - A case of retropharyngeal abscess in a child is reported. The patient was nontoxic appearing, afebrile, and had minimal symptoms. The case is used to highlight the high index of suspicion that may be necessary to diagnose the condition. Diagnostic approaches, emergency treatment, and disposition of patients are discussed. PMID- 8476458 TI - Venous air embolism following orogenital sex during pregnancy. AB - Venous air embolism is an infrequent complication of pregnancy but may occur if air is blown into the vagina during orogenital sex. Air passes beneath the fetal membranes and into the circulation of the subplacental sinuses, invariably causing death to both mother and fetus within minutes. Reported is the case of a nonfatal air embolism following vaginal air insufflation in the 38th week of pregnancy. The hospital course was complicated by hypotension, metabolic acidosis, acute neurologic changes, and emergency caesarean section with eventual fetal demise. Clinical and laboratory abnormalities as well as treatment measures are discussed. Familiarity with this syndrome is essential if prompt and appropriate therapy is to be rendered. PMID- 8476459 TI - Cervical spine trauma in children: Part I. General concepts, normal anatomy, radiographic evaluation. PMID- 8476460 TI - Emergency cardiac pacing. PMID- 8476461 TI - Cases in electrocardiography. PMID- 8476462 TI - Ketamine dissociative sedation in pediatric emergency medical practice. PMID- 8476463 TI - The role of emergency medicine in a teaching hospital: decision making in an uncontrolled environment. PMID- 8476464 TI - Severe reaction to "natural testosterones": how safe are the ergogenic aids? PMID- 8476465 TI - Unusual complication of central venous catheterization. PMID- 8476466 TI - Blunt abdominal trauma due to a goat assault. PMID- 8476467 TI - Prolonged bradyasystole and seizures following intravenous adenosine for supraventricular tachycardia. PMID- 8476468 TI - Assessment of acute iron poisoning by laboratory and clinical observations. AB - A survey of medical records at a tertiary children's medical center was performed to determine whether selected laboratory and clinical observations and the serum iron concentration exceeding the total iron-binding capacity serve as indicators of acute iron poisoning. Patients were hospitalized for treatment of iron poisoning during January 1976 through June 1992. A total of 128 patients were identified; 92 met selection criteria and 65 had a serum iron concentration and total iron-binding capacity obtained simultaneously. The present study was unable to confirm that vomiting, diarrhea, leukocytosis, hyperglycemia, and radiopacities were associated with a serum iron concentration in excess of 300 micrograms/dL (54 mumol/L); only one observation, coma, was associated (P < .02) with a serum iron greater than 500 micrograms/dL (90 mumol/L). Coma, radiopacities, leukocytosis, and an elevated anion gap will be concurrently present (predictive value positive = 100%) when the serum iron concentration is greater than 500 micrograms/dL; moreover, they will be absent collectively (predictive value negative = 95%) when the serum iron concentration is below 500 micrograms/dL. Individually, these signs and symptoms have a low positive predictive value, but the absence of any one of these variables is likely to be associated with serum iron concentrations less than 500 micrograms/dL (predictive value negative > or = 93%). The ratio of serum iron concentration to the total iron-binding capacity was not associated with symptoms of systemic iron toxicity or presence of vin rose urine after parenteral deferoxamine administration. A serum iron concentration in excess of the total iron-binding capacity may not identify patients with serious iron poisoning. PMID- 8476469 TI - The ferning and nitrazine tests of amniotic fluid between 12 and 41 weeks gestation. AB - Most studies investigating the usefulness of ferning and nitrazine methods for detecting the presence of amniotic fluid following ruptured amniotic membranes have employed samples from vaginal pooling. Reported accuracies are 84 to 100% for the ferning test and 87 to 97% for the nitrazine test. Our study was designed to determine if these tests are applicable throughout gestation. Samples were obtained from amniocenteses between 14 and 42 weeks. Part I: Of 112 samples allowed to dry on a slide for 3 minutes only, 86.6% were ferning positive and 100% were nitrazine positive. Flame-drying increased the presence of ferning to 96.4%. Part II: 363 samples were allowed to dry completely for up to 10 minutes. All samples were ferning and nitrazine positive. Part III: 17 samples were tested for ferning and nitrazine at 1 hour, and again at 1 week. Sixty-six samples were tested within 1 week and again at 2 weeks. All samples remained ferning and nitrazine positive. Therefore optimal analysis of suspected amniotic fluid occurs when specimens are air-dried for 10 minutes. These tests may be reliably performed at gestations of 12 to 41 weeks. PMID- 8476470 TI - Sonographic measurement of the fetal iliac bone: growth and relation to femur length in assessment of gestational age. AB - Diagnostic ultrasonography has given us the opportunity to diagnose several congenital malformations in utero. Skeletal dysplasias is a heterogeneous group of disorders of the skeleton. Although disorders of bone growth are often diagnosed in utero, it is usually a general diagnosis because the exact syndrome cannot be specified. This is due to the fact that many anomalies of the skeleton have similar features. The wing of the iliac bone can be either affected or normal in skeletal dysplasias and its appearance may help in the differential diagnosis. This study was undertaken to establish values for the width of the iliac bone wing during normal gestations and thus enable us to use it in the evaluation of fetal growth and the recognition of specific congenital anomalies. PMID- 8476471 TI - Ultrasonic evaluation of kidney volume in term and preterm infants. AB - Kidney volume in relation to gestational age, birthweight, and height was determined in 121 infants, 58 females and 63 males, with gestational ages from 23 to 43 weeks (mean, 33.3) and birthweight from 430 to 4600 gm (mean, 1982 gm). The kidney volume was measured using a real-time linear computed ultrasound scanner, with a 5 MHz transducer. The renal volume was calculated from outer kidney diameters using the volume formula for an ellipsoid. In the infants studied, mean volume of the right kidney was 6.0 ml (range, 1.4 to 13.8 ml), and of the left kidney 6.6 ml (range 1.5, to 15.6 ml), with no significant difference. A highly significant correlation was found between the volume of both kidneys and either gestational age, or birthweight, or height, with r values ranging from 0.81 to 0.92. The best correlation was observed with birthweight. No significant difference was found between males and females. PMID- 8476472 TI - Is fetal blood sampling associated with increased beta-endorphin release into the fetal circulation? AB - This study was conducted to determine whether fetal blood sampling during the second trimester is associated with changes in circulating fetal beta-endorphin (BE) concentrations. We measured BE concentrations in 68 paired fetal and maternal blood samples obtained between 18 and 28 weeks' gestation. Patients were divided into a control group (n = 50), if the fetal blood samples were obtained by a single umbilical cord puncture, or multiple insertion group (n = 18), if multiple cord punctures were required to obtain a sample. The mean (+/- SE) fetal BE value for the multiple insertion group was significantly higher than BE levels from the control group (771.2 +/- 79.2 pg/ml versus 107.1 +/- 11.7 pg/ml; p < 0.001]. This elevation did not appear to be related to acidosis, since no differences in fetal umbilical pH were observed between the two groups. Fetal BE levels from the control but not from the multiple insertion group significantly correlated with maternal values (Spearman rank r = 0.59; p < 0.001 vs r = -0.08; p > 0.5). In neither group did fetal BE levels correlate with gestational age. These findings indicate that multiple cord punctures at the time of fetal blood sampling are associated with significant increases in BE release. Furthermore, although a maternal or placental contribution to steady state circulating fetal BE cannot be excluded, it would seem that the fetus itself is the primary source of elevated circulating BE levels following multiple cord punctures. PMID- 8476473 TI - Corticotropin-releasing hormone and cortisol in cord plasma in relation to gestational age, labor, and fetal distress. AB - Concentration of corticotropin-releasing hormone (CRH) has earlier been found to increase greatly in maternal plasma during the last trimester of normal pregnancy and even more in preeclampsia. This CRH is thought to be of placental origin, and it may stimulate maternal or fetal pituitary adrenal axis. We studied CRH in umbilical cord venous plasma in relation to gestation, labor, and fetal distress. There was a great maternal-to-fetal concentration difference in plasma CRH levels, a hundredfold at term pregnancy, suggesting that the placenta releases CRH mainly into the maternal rather than into the fetal circulation. Length of gestation or the mode of delivery did not affect CRH levels in cord plasma. Cord CRH levels were higher (median, 24.1, range, 14.2 to 67 pmol/liter) in six preterm infants with chronic fetal distress, born to mothers with severe preeclampsia and in nine infants born after premature rupture of membranes (median, 17.0, range, 7.65 to 53 pmol/liter), than in 12 preterm control infants born after uncomplicated pregnancy (median, 6.3 range, 1.0 to 27.5 pmol/liter). No significant correlation was found between CRH and cortisol levels in cord plasma. Increased cortisol levels in cord plasma were associated with spontaneous vaginal delivery but not with chronic fetal distress. These findings demonstrated that placental release of CRH into the fetal circulation may be increased in pregnancy complications with chronic fetal distress but failed to prove any relationship between placental CRH and fetal adrenal function. PMID- 8476474 TI - Doppler flowmeter-assessed circadian rhythms in neonatal cardiac function, family history, and intrauterine growth retardation. AB - This study examines the circadian variation of aortic blood flow velocity, acceleration, and distance of stroke, assessed every 4 hours for 24 hours by Doppler ultrasound in 88 human newborns. Groups 1 and 2 involve neonates with a negative family history of high blood pressure or myocardial infarction monitored during the first day or between the second and tenth days postpartum, respectively; groups 3 to 6 are 2- to 10-day-old babies with a positive family history of high blood pressure (group 3) or of myocardial infarction (group 4) or with a negative family history and intrauterine growth retardation (group 5) or born prematurely (group 6). Cosinor analyses demonstrate a circadian rhythm for all variables in groups 2 and 5 (p < 0.001), with overall high values occurring around 17:40. In group 2, a circadian rhythm remains demonstrable in boys and girls considered separately, and mostly so in arbitrary subgroups of different sizes, with only slight differences in rhythm parameters among them. These results show that, with relatively small samples, reproducible circadian rhythms of cardiac function can be detected shortly after birth in neonates with a negative family history of high blood pressure or myocardial infarction. PMID- 8476475 TI - Direct stimulation of urokinase, plasmin, and collagenase by meperidine: a possible mechanism for the ability of meperidine to enhance cervical effacement and dilation. AB - Current hypotheses suggest that the degradation of cervical collagen and elastin leads to cervical effacement and dilation during labor. The collagenolytic activity is thought to be initiated through the conversion of latent (pro)collagenase to active collagenase by the plasmin formed from plasminogen or by other proteases similarly formed from their inactive zymogens. We presently demonstrate that meperidine stimulates the activity of several enzymes in the proteolytic cascade leading toward proteolysis of connective tissue proteins. Meperidine in its therapeutic concentration range produces a 26% stimulation of urokinase activity on substrate S-2444, a 39% stimulation of plasmin activity on substrate S-2551, and a 33% stimulation of collagenase activity on 14C-labeled globin substrate. These direct effects on the enzyme activities are noted in vitro with the purified enzymes and were confirmed with several small molecular weight chromogenic substrates and with 14C-globin protein substrate. Oxytocin at levels found during active labor fails to stimulate the in vitro activity of purified urokinase, plasmin, collagenase, trypsin, or tissue-type plasminogen activator. The effect of meperidine on the proteolytic enzymes suggests that its ability to promote cervical effacement and distention during labor may be at least partially due to a meperidine-induced stimulation of cervical proteases. PMID- 8476476 TI - Obstetric and neonatal outcome in fetuses with absent end-diastolic velocities of the umbilical artery: a case-controlled study. AB - Absence of end-diastolic velocities (AEDV) is the most severe waveform abnormality detected by Doppler ultrasound examination of the umbilical artery. It is associated with fetal hypoxemia and acidemia. If AEDV predisposed to more neonatal complications, then it might be an indication for earlier delivery. This was investigated in 21 preterm fetuses with AEDV who were matched for gestational age at delivery with 21 with end-diastolic velocities. All fetuses were delivered electively before 36 weeks' gestation of mothers who were hypertensive. The fetal heart rate (FHR) variability, birthweight, and umbilical arterial blood pH were significantly lower in the AEDV group. However, the neonatal outcomes were similar except for less severe hyaline membrane disease and lower initial platelet counts in the AEDV group. At present, fetuses with umbilical arterial AEDV need not be delivered earlier than indicated by the FHR pattern, nor should neonatal management be altered on the basis of antenatal AEDV. PMID- 8476477 TI - Respiratory compliance assessed from chest expansion and inflation pressure in ventilated neonates. AB - We evaluated a bedside method of assessing respiratory compliance from chest expansion, which is judged by eye and classified into three tidal volume categories, and from the inflation pressure read on the respirator's manometer. Compliance assessed by this method was compared with the compliance measured by the injection technique in 45 randomly chosen newborns ventilated for various diseases. The compliance assessed from chest expansion and inflation pressure correlated significantly with the measured compliance (r = 0.86, p < 0.001). Interobserver reliability was acceptable for clinical practice and improved within 6 months of training (weighted kappa = 0.67 versus 0.86). Within ten individuals, changes of compliance assessed by this method were also significantly correlated with those of measured compliance (r = 0.85, p < 0.01). This method, termed "optical compliance," is instantaneously and always available for all patients on ventilators without any additional apparatus and thus might improve the assessment of respiratory function in routine care and emergency situations. PMID- 8476478 TI - Acid-base significance of meconium discovered prior to labor. AB - Although the significance of meconium in the amniotic fluid diagnosed during labor remains problematic, there is little information regarding the significance of meconium discovered prior to labor. The present study consisted of 40 term pregnancies with meconium found at amniocentesis for lung maturity (n = 7) or elective cesarean section (n = 33) and 40 uncomplicated, control pregnancies with clear amniotic fluid at elective cesarean section. The mean umbilical artery (UA) blood pH was 7.26 in the meconium group and 7.28 in the control group. Overall, the frequency of fetal acidemia (UA pH < 7.20) was 15% (6 of 40) of the infants in the meconium group versus 8% (3 of 40) in the control group (p = 0.24). All nine of these infants had a respiratory acidosis defined as a UA blood pH less than 7.20 with normal bicarbonate and elevated carbon dioxide pressure. Importantly, none of the neonates had metabolic acidemia and all had uncomplicated hospital courses. All of the pregnancies reported were promptly delivered because of meconium and we therefore cannot recommend nonintervention when meconium is diagnosed in the antepartum period. Meconium discovered prior to labor is not necessarily a marker of immediate or chronic fetal compromise. PMID- 8476479 TI - Placental chorioangioma: prenatal diagnosis and clinical significance. AB - We report the prenatal diagnosis of placental chorioangioma in a 32-week intrauterine pregnancy associated with polyhydramnios and enlarged fetal cardiac size that resulted in intrauterine fetal death. Ultrasound appearance, pathophysiology, and clinical significance of this entity are discussed. PMID- 8476480 TI - The frequency of hypoglycemia in full-term large and small for gestational age newborns. AB - Although various authors recommend screening for hypoglycemia in large for gestational age (LGA) and small for gestational age (SGA) newborns, the frequency of hypoglycemia in these infants, using a recent definition of hypoglycemia, and the proper duration of screening are not documented. We determined chromogen test strip blood glucose values at ages 1, 2, 3, 6, 12, 24, 36, and 48 hours in full term LGA and SGA infants whose mothers were not diabetic. Serum glucose determination was immediately done if a test strip reading was less than 40 mg/dl. Hypoglycemia was defined as a serum glucose less than 35 mg/dl at less than 3 hours of age, less than 40 mg/dl at 3 to 24 hours of age, and less than 45 mg/dl at more than 24 hours of age. The frequency of hypoglycemia in LGA infants was 8.1% (95% confidence interval [CI] 5.0 to 11.2%), and in SGA infants, 14.7% (95% CI 9.8 to 19.6%). The mean age at which hypoglycemia occurred was 2.9 hours (range, 0.8 to 8.5) in LGA infants, and 6.1 hours (range, 0.8 to 34.2) in SGA infants. There were no differences in other possible risk factors between the hypoglycemic and euglycemic infants except that in SGA infants meconium-stained amniotic fluid (40% vs 20%, p = .001), maternal preeclampsia (27% vs 8%, p = 0.0056), and male sex (29% vs 9%, p = 0.029) were more common in hypoglycemic than in euglycemic infants. These data suggest that screening for hypoglycemia in LGA infants whose mothers are not diabetic may be stopped after 12 hours, but should continue for 48 hours in SGA infants. PMID- 8476481 TI - The extremely low birthweight infant: the twenty-first century dilemma. AB - The survival rate of very low birthweight infants (weighing less than 1500 gm) has dramatically increased over the past two decades. Consequently, high-tech intensive care is offered to an increasing number of infants with borderline viability, previously considered as miscarriages. We reviewed the most recent literature on the results of intensive care used in the subgroup of extremely low birthweight infants, weighting less than 750 gm or 800 gm. Since definitions, management policies, and follow-up reports in this group of newborns are not consistent, the important statistical variables of incidence, mortality, and morbidity are incomplete and severely biased. In the past decade there was a growing tendency toward using a more active approach in caring for these infants. Most of the success is among the infants weighing 750 to 800 gm, with a survival rate in the range of 33 to 62%. However, the overall improvement in survival is small, with an extremely poor outlook for infants below 600 gm. The morbidity rate in the survivors is alarmingly high, reaching 70% and most common in infants with birthweight less than 600 gm. The available data show that virtually for every "healthy" surviving extremely low birthweight infant there is also at least one surviving child who is moderately to severely handicapped. The overall consequences and implications of high-tech care of these borderline viability infants, once considered as nonviable, are not necessarily improved over those of the former, less aggressive, approach. Since these results have grave consequences for the involved families and society, we urgently need to involve these parties more actively in decision making. PMID- 8476482 TI - Vasopressinase-altered vasopressin elevates arterial pressure in anesthetized rats. AB - Transient diabetes insipidus of pregnancy (TDIP) is associated with elevated activity of vasopressinase, a plasma enzyme that opens the vasopressin (AVP) ring to produce a linear peptide that we have named vasopressinase-altered vasopressin (VAV). VAV may play a role in the pathogenesis of the arterial hypertension associated with TDIP. We sought to determine if VAV elevates arterial pressure, the potency of VAV relative to that of AVP, and whether the peptide binds to the vascular AVP receptor. AVP was incubated with vasopressinase and VAV was separated from residual AVP by high-pressure liquid chromatography. Intravenous bolus administration of VAV or AVP to ganglionic blocked rats produced dose dependent increases in arterial pressure, with VAV demonstrating approximately 6000-fold lower potency than AVP. Vasopressin receptor blockade abolished the response to both AVP and VAV. These results suggests that high levels of VAV may contribute to the hypertension seen in TDIP. PMID- 8476483 TI - Acquired tracheoesophageal fistula in a premature infant. AB - A fatality from an acquired tracheoesophageal fistula (TEF) in a very low birthweight premature infant is presented. Neonatal tracheal and esophageal injuries related to endotracheal (ET) intubation are discussed. The infant had important risk factors for the development of subglottic stenosis: birthweight less than 1000 gm, prolonged positive pressure ventilation, and repeated ET intubation. The pathologic examination was consistent with acquired fistula formation resulting from a combination of preexisting subglottic stenosis and prolonged and repeated ET intubation. The recognition of clinical signs of an acquired TEF, as observed in our patient, followed by expeditious diagnostic testing may be lifesaving. PMID- 8476484 TI - Raised serum gravidin levels are associated with pregnancy-induced hypertension. AB - It has recently been reported that synthesis of the vasodilatory prostaglandin, prostacyclin, is decreased in human pregnancy-induced hypertension (PIH). Prostaglandin production is regulated mainly by the enzyme phospholipase A2. We report here that serum levels of a potent phospholipase A2 inhibitor (gravidin) were elevated during early pregnancy in women who later developed PIH compared with those who remained normotensive throughout pregnancy. It is suggested that high circulating levels of this potent phospholipase inhibitor may account for the reported decrease in prostacyclin synthesis and contribute to the development of pregnancy-induced hypertension. PMID- 8476485 TI - Survival in an infant with a prenatally diagnosed Meckel syndrome variant. AB - An infant with occipital encephalocele and unilateral multicystic kidney, diagnosed prenatally, was considered to have a variant of the Meckel syndrome (MS). This case is exceptional in that the infant was alive and healthy following surgical repair of the encephalocele, with normal function of the unaffected kidney, at age 5 months. Based on this experience, in fetuses or infants with MS, thorough evaluation of both kidneys is imperative prior to suggesting either termination of pregnancy, or withholding of life-sustaining medical treatment in infants already delivered. PMID- 8476486 TI - Prolonged survival of two anencephalic infants. AB - Two infants with anencephaly survived for 7 and 10 months without the need for prolonged assisted mechanical ventilation. One infant prospectively fulfilled all four criteria of the Medical Task Force on Anencephaly, making diagnosis almost certain. Prolonged survival of anencephalic infants is important not only to provide adequate counseling, but also for its relevance to organ transplantation. PMID- 8476487 TI - Thermoregulation of pregnant women during aerobic exercise on land and in the water. AB - Seven women in their 25th week of pregnancy exercised for 20 minutes on a cycle ergometer at 70% of their maximal heart rate on land and in the water (30 degrees C) to compare thermoregulatory responses. Rectal temperatures increased 0.5 +/- 0.1 degrees C during the land trial and only 0.2 +/- 0.1 degrees C during the water trial (p < 0.05). Mean body temperature rose 0.6 +/- 0.2 degrees C during the land trial, but declined -0.3 +/- 0.1 degrees C during the water trials (p < 0.05). Land exercise caused greater heat storage and sweat loss. The results suggest that normal pregnant women can maintain thermal balance during 20 minutes of exercise at 70% maximal heart rate, whether on land or in the water. Thus, for normal, average fit, pregnant women who wish to participate in a moderate exercise program, heat stress is probably not a major concern. PMID- 8476488 TI - General anesthesia for surgical repair of intracranial aneurysm in pregnancy: effects on fetal heart rate. AB - A 30-year-old nulliparous woman underwent surgery for a ruptured aneurysm of the left vertebral artery in gestational week 27. The fetal heart rate (FHR) was monitored continuously with an abdominal Doppler transducer. Anesthesia was induced with midazolam, fentanyl, and thiopental and maintained with fentanyl, isoflurane, and nitrous oxide 67% in oxygen. Surgery was performed under moderate hypotension (mean arterial pressure +/- 70 mmHg) and moderate hyperventilation (arterial carbon dioxide pressure +/- 33 mmHg). There was a complete disappearance of FHR variability without decelerations or bradycardia. In the night following surgery, the patient was sedated with large parenteral doses of midazolam and fentanyl. Despite this sedation, some FHR variability reappeared within 40 minutes after discontinuation of the inhalation anesthetics. After discontinuation of parenteral midazolam and fentanyl, normal FHR variability returned within 60 minutes. In week 41 of pregnancy, a healthy girl of 4015 gm was born. PMID- 8476489 TI - Mathematical modeling of fetal organ growth using the Rossavik growth model: II. Adrenal gland. AB - Growth of the fetal adrenal gland has been monitored by measurements of the circumference (AGC) and area (AGA) of the adrenal gland from 16 to 40 weeks menstrual age. Growth curves for these parameters have been determined using a Rossavik growth curve models [P = c(t)k + s(t)]. R2 values of 86.2 and 91.1% were obtained for AGC and AGA, respectively. Variability analysis indicated a progressive increase in variability with menstrual age for these two parameters. Variability data were used with the growth curve models to determine standard curves for AGC and AGA. These standard curves provide a superior means for evaluating the adrenal growth in the fetus and the fetal status in utero in high risk pregnancies. PMID- 8476490 TI - Building antibodies from their genes. PMID- 8476491 TI - [Expression of recombinant proteins in the milk of transgenic animals]. AB - The bulky production of recombinant proteins can be achieved by procaryotes or eucaryotes cells. Cells from higher eucaryotes may be required when proteins have to be modified post-transcriptionally (glycosylation phosphorylation, cleavage, folding...). Cells from higher vertebrates in culture are used to prepare proteins like human factor VIII and erythropoietin. The use of transgenic organism has been suggested to reach the same goal. Indeed a whole living organism allows a very potent amplification, the number of cells involved in the biosynthesis of the recombinant proteins being very numerous and in the best metabolic conditions. Biological fluids (blood, milk, insect hemolymph, egg white...) and possibly organs from transgenic animals are a priori the best sources of recombinant proteins. Blood is abundant and it is a by-product of slaughter house. Its composition is relatively complex and the circulating recombinant proteins may heavily alter health of animals. Milk is very abundant, its composition is relatively simple, it is poor in proteolytic enzymes and it can be collected easily. Hemolymph from insects is relatively scarce. Egg white will be a possible source of recombinant proteins, when transgenesis has become more accessible in birds. Organs from transgenic animals should be solicited only when a particular cell type is required for the biosynthesis of the recombinant proteins. Milk appears therefore, presently, as the best source of recombinant proteins from transgenic animals. About 15 public and private laboratories try to use these techniques. They consist in preparing vectors containing regulatory regions of one of the milk proteins genes and the coding part (cDNA or gene) of the corresponding proteins to be produced. The transfer of these gene constructs to mouse, rabbit, sheep, goat, pig, shows that these techniques are indeed very promising. A single protein, human alpha 1-antitrypsin produced in milk of transgenic sheep, has presently reached the preparation at an industrial scale. This method has two theoretical limitations: 1) some of the proteins secreted in milk may be not matured as their native counterparts. Experiments carried out so far (about 20 proteins has been produced at an experimental scale) indicate that the mammary cell is able to achieve glycosylation in a correct way; 2) a significant proportion of the recombinant proteins migrate from the alveolar compartment of the mammary gland to blood circulation and they can alter health of lactating animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8476492 TI - Viral inactivation and reduction in cellular blood products. AB - Even though the risks associated with the transfusion of blood products are lower than ever before, considerable efforts are being employed to improve the safety of the blood supply. Based upon available data, a six log (99.9999%) reduction in virus level from screened and tested blood components should significantly reduce or eliminate the risk of post-transfusion infection. The objective has been to identify "generic" methods, that is, one that would be applicable to all virus. For red cells, physical and chemical approaches have been studied; for platelets, the approaches have been limited to chemical. The physical methods include depletion of leukocytes by filtration, removal of plasma by washing, and viral inactivation by heat. Among the chemicals investigated to inactivate or help displace virus are ozone, detergents, and hypochlorous acid. Several photochemicals have also received intensive investigation: merocyanine 540, a benzoporphyrin derivative, aluminum phthalocyanine, and methylene blue. For platelets, photochemical inactivation methods using merocyanine 540, and two psoralen derivatives, 8-methoxypsoralen (8-MOP) and aminomethyl trimethyl psoralen (AMT), have also been studied. Approaches which include washing are not suitable. For the most part, either viral removal or inactivation has been insufficient, or red cell or platelet damage unacceptable. However, there are a few indications that at least inactivation of a specific virus, such as HIV, may be possible without major cell damage. These studies are in their early stages and significant work remains. If feasibility is clearly shown in vitro, it is likely that in vivo primate studies to demonstrate safety and efficacy will be required. PMID- 8476493 TI - [Industrial pasteurization of plasma and criteria of quality]. AB - The approach followed in the design of a large-scale pasteurization treatment (60 degrees C for 10 hours in the liquid state) of fresh frozen plasma is presented. Various aspects thought to influence the viral safety of such a product are discussed. They are based largely upon the fact that, although it is subjected to a specific viral inactivation treatment, this plasma does not benefit from any fractionation steps known to participate in the potential elimination of infectious agents during the manufacture of plasma derivatives. Consequently, the plasma is obtained from regular plasmapheresis donors, and the plasma donations used to make the pool must be negative for anti-HIV-1 and -2, anti-HCV, anti-HBc, anti-HTLV-1 and -2, HBs antigen and parvovirus B19 antigen, and have a normal level of ALT. The batch size is limited to 100 plasma units to limit the potential infectious risk associated with very large batches, especially if an infectious agent, resistant to pasteurization, is present. Pasteurization has been chosen for this procedure, as applied to plasma derivatives, has been shown to inactivate a broad spectrum of viruses, both enveloped and non-enveloped. The process is relatively simple. The frozen plasma units are opened, and the plasmas are mixed and thawed at 30 degrees C to avoid the formation of cryoprecipitate. The liquid plasma is transferred to a sterilized container and stabilizers are added. The mixture is then transferred to the pasteurization unit to be heat treated at 60 degrees C for at least 10 hours under gentle mixing. Following cooling, the mixture is ultrafiltered to eliminate the stabilizers and to concentrate the plasma pool to its initial volume. The plasma is sterile filtered, then dispensed into bottles and frozen. Virus validation of this pasteurization process, carried out by independent virology laboratories, have confirmed the ability of the process to inactivate more than 4 to 6 logs of non enveloped or enveloped, DNA or RNA, viruses, including HIV-1 and Sindbis virus, in less than 5 hours of heat-treatment. The biological characteristics of the pasteurized plasma include a good preservation (75 to 95%) of the activity of clotting factors, including FI, FV, FVIII, FXI, and FXIII, and protease inhibitors. The overall clottability of the plasma, as expressed by the APTT, is almost unchanged.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8476495 TI - [The behavior of Penicillium spores in air filters for automobile interiors. Testing of germination and propagation under static and dynamic test conditions using microscopic and microbiologic methods]. AB - Microbiological tests show, that 3-layer car-air filters (Polycarbonate microfiber type AF 901) are not a substrate for fungi frequently present in outdoor air. Microscopical investigations of the filter samples, which were exposed to Penicillium spores under static and dynamic conditions show no growth and no germination. The particles of dust which are trapped in the car-air filter, have no components with fungicidal effect, but include substances for inhibition of spore germination. In static model experiments (without air stream) already driven car-air filters were tested and fungal growth was obtained by very high concentrations of substrate and spores. On the other hand, however, in dynamic tests (with air stream) fungal growth cannot be detected, because the liquid humidity is absent. PMID- 8476494 TI - [Environmental medicine group diagnosis of children--studies from 1982 to 1990. Review]. AB - In the period of 1982-1990 a total of 5760 children (2893 boys, 2816 girls) were examined in the frame-work of the Clean Air Programme Rhine-Main: from the polluted Rhine-Main area 2511 children (Wiesbaden 1682, Frankfurt since 1985, 825), from the control areas 3153 children (Freiburg area 1937, Starnberg area 1316). Healthy children living in the industrialised Rhine-Main area exhibited alterations of the following parameters compared with healthy children living in the less polluted control areas: Long-term alterations, enlarged and fissured, rough palatine tonsils, palpably enlarged cervical and mandibular lymph nodes, Short-term alterations, erythrocyte count: from 1981-1988 relatively smaller numbers, from 1988-1990 equalized to the scatter range of controls, hemoglobin values: corresponding to erythrocyte counts, activity of lymphocyte nucleoli: increased until 1985, later on equalized, lymphocyte count: reduced, T8 suppressor cell count: decreased, chemiluminescence of granulocytes: increased, palatine tonsils: altered microbial contamination with contact germs, altered physiological resident flora, heavy metals (Pb, Cd) in hair: from 1982-1990 increased, then slowly reduced corresponding to the results of the ambient air analyses. These findings indicate an increased inclination for reaction of the healthy juvenile organism in the sense of biological adaptation to long-term stress, i.e. living for years in an area with air pollution, and are also in good agreement with the measuring values characterising the ambient air quality. PMID- 8476496 TI - Comparison of glass wool and glass powder methods for concentration of viruses from treated waste waters. AB - Enumeration of cultivable virus particle in sewage requires the samples to be concentrated. Two adsorption-elution methods, the glass wool cartridge method and the glass powder fluid layer method were compared. Firstly, it was demonstrated that virus could be readily recovered from the head, first 25 ml, of eluate of glass wool rather than from a reconcentration of the entire eluate, either by organic flocculation: 83% of positivity vs 44% respectively or double precipitation by PEG: 85% of positivity vs 61% respectively. Concentration on glass wool allowed the rescue of a greater number of positive samples (33/35) than on glass powder (16/35) as well as a higher mean titer of indigenous viruses, respectively 19 MPNCU/l vs 6 MPNCU/l (F1(34) = 36.02, P < 0.0001). Enteroviruses were the most frequently isolated viruses: found in 34/35 samples by either method, in 32/35 samples by glass wool, and in 14/35 samples by glass powder. Of the 12 enterovirus types identified by either method, a majority was Echovirus 6 (10 samples), Echovirus 11 (7 samples), Coxsackievirus B5 (4 samples) and also Coxsackievirus A7, A16, A21, B1, B6, Echovirus 1, 4, 12 and 19. Adenovirus types 1 and 5 were isolated from 4 samples by either method. PMID- 8476497 TI - Prevalence of Legionella species, serogroups, and monoclonal subgroups in hot water systems in south-eastern Germany. AB - To study the contamination of hot water systems in south-eastern Germany 75 houses were selected and water samples were collected from peripheral hot water taps, shower heads and in a few cases from central water storage tanks. A total of 661 water samples were cultured. 186 (27.7%) were positive for legionellae. In 68% of hospitals, 50% of outpatients departments, 58% of dental offices, 85% of public buildings and 65% of private households in large buildings legionellae could be isolated. Most samples contained legionellae in the range of 1-100 colony forming units (cfu) per ml, the highest concentration was 4000 cfu/ml. Isolated strains were typed using absorbed rabbit sera prepared against the ATCC type strains by the indirect immunofluorescence test. Legionella pneumophila serogroup 1, 2, 5, 6, and 10 strains were further subtyped using monoclonal antibodies. A total of 1548 colonies were serotyped. If the same species, serogroup and subtype in a given water system was considered to be the same strain, 77 different strains were isolated. 31 buildings contained one, 11 buildings two, 3 houses three and one building six different strains. 72 strains belonged to the species Legionella pneumophila and 5 strains were non-pneumophila species. Legionella pneumophila serogroups 1, 3, 6, and 10 were most frequently isolated with 22%, 14%, 16% and 18%, respectively. Among the serogroup 1 strains, the monoclonal subgroup Bellingham was the most commonly found. PMID- 8476498 TI - [Epidemic occurrences of multiresistant Acinetobacter baumannii strains in a neonatal intensive care unit]. AB - In a period of nine months (May 1991 to January 1992), 39 infants were colonized with Acinetobacter baumannii in a paediatric intensive care unit. Colonization was observed mainly in premature infants, weighing between 680 g and 2,000 g, who were artificially ventilated. Shortly after birth, A. baumannii was isolated regularly from tracheal washings, and less frequently from other material, such as gastric juice, catheter tips, and umbilical swabs. In older children or adults, the bacteria were found only in very low frequency. In the intensive care unit, A. baumannii could be isolated from tap water, sinks, water traps of the ventilation devices, the inner wall of incubators, and from the hands of medical personnel. Patients strains of A. baumannii, and those isolated monitoring the intensive care unit had an identical biochemical profile and a similar pattern of antimicrobial resistance, as well as a similar reaction in other typing methods. Anti-infective measures are discussed. PMID- 8476499 TI - The influence of culture conditions on the susceptibility of Salmonella typhimurium in the Salmonella mutagenicity test. AB - To determine the variability of tester strain susceptibility in the Salmonella mutagenicity assay and to optimize the culturing procedure we examined the influences of the overnight culture period (12-16 h), the use of an additional short-term culturing procedure (1-4 h) and the Salmonella density (cfu/plate) on the rate of revertants per plate. As tester strains we used Salmonella typhimurium TA97, TA98, TA100 and TA102. As shown previously for other microbial genotoxicity short-term tests (i.e. with Escherichia coli PQ37), we observed the highest susceptibility of the Salmonella strains, i.e. the highest amounts of revertants per plate, when using a 12 h overnight culture followed by a 2 h short term culturing procedure. We calibrated the bacterial count to 100 x 10(6) cfu per assay by photometric measurement (600 nm). Initially, we used 0-1 nmole 2,4,7 trinitro-9-fluorenone with S. typhimurium TA97, 0-15 nmole daunomycin with strain TA98, 0-25 nmole sodium azide with strain TA100 and 0-15 nmole methylmethanesulfonate with strain TA102 as reference compounds in the standard plate incorporation test. Subsequently, to evaluate the results of the culturing procedure variations we examined 22 well-known mutagenic and direct-acting (-S9 mix) compounds out of different chemical classes using both the standard and a modified culturing procedure. The comparison of these results showed a 64% (for 4 nitroquinoline-N-oxide) to 421% (for sodium azide) increased amount of revertants for the modified test protocol. PMID- 8476500 TI - [Biological safety investigation of the production of human insulin using genetically altered E. coli K-12 cells. 2. Plasmid transfer by mobilization and cointegrate formation under environmental conditions]. AB - Plasmid transfer by mobilization and cointegrate formation was tested with expression plasmids for human insulin in laboratory media and in river water samples. Plasmid pLIZP4 which carries a nic/bom sequence could only be mobilized after cloning of mobilization genes. Plasmid mobilization could be detected in laboratory media only, not in river water samples. The Nic/Bom plasmid pSW3 could be transferred by cointegrate formation in laboratory media at 30 degrees C and 37 degrees C, not at room temperature or in river water. The results allow the conclusion that no transfer of the plasmids pLIZP4 and pSW3 will take place by mobilization or cointegrate formation under environmental conditions. PMID- 8476502 TI - Peptide nucleic acids (PNAs): potential antisense and anti-gene agents. AB - The binding of peptide nucleic acids (PNAs) T10-LysNH2, T5CT4-LysNH2 and T2CT2CT4 LysNH2 to double-stranded DNA targets A10, A5GA4 and A2GA2GA4 was studied by nuclease S1 probing. It is found that the PNAs bind preferentially to their complementary targets, weaker to targets containing one mismatch and not to targets containing two mismatches. Using an RNA polymerase T3 in vitro transcription system, it is found that a PNA T10-LysNH2 bound downstream from the promoter causes transcription elongation arrest at the PNA binding site only when the PNA is bound to the template strand. Finally, it is shown that primer extension by Taq DNA polymerase on a single-stranded template is arrested at an occupied PNA T10 binding site. These results are discussed in relation to PNAs as potential anti-sense and anti-gene drugs. PMID- 8476503 TI - Stabilities of duplexes and triplexes of dA19 + dT19 with alternating methylphosphonate and phosphodiester linkages. AB - Results from UV thermal melting, polyacrylamide gel electrophoresis and circular dichroism (CD) experimetns are used to compare stabilities of complexes formed from 1:1 and 1:2 molar ratio mixtures of dA19 or dA*P19 (alternating phosphodiester and methylphosphonate linkages on the A chain) with dT19 or dT*P19 (alternating phosphodiester and methylphosphonate linkages on the T chain). Complexes formed from 1:1 and 1:2 molar ratio mixtures of dA*P19 with dT19 are more stable than the respective unmodified 'parent' complexes, but less stable than complexes of dA*19 (17 methylphosphonates on the A chain) + dT19. At 0.1 M Na+ complexes containing dT*P19 are less stable than those with dT19, yet more stable than complexes containing the highly modified dT*19 (17 methylphosphonates on the T chain). A value of 2.6 kcal/mol base triplets is calculated for delta H of dA19.2dT19-->dA19.dT19+dT19. PMID- 8476501 TI - Growth inhibition of human tumor cell lines by antisense oligonucleotides designed to inhibit p120 expression. AB - The human nucleolar antigen p120 was detected with an anti-p120 monoclonal antibody (MAbp120) in most human malignant tumors (Freeman et al., Cancer Research, 48, 1244-1251, 1988). Stable transfection of the sense p120 cDNA caused malignant transformation of NIH/3T3 cells in vitro, and the antisense p120 constructs markedly delayed the growth of these transformed cells (Perlaky et al., Cancer Research, 52, 428-436, 1992). Several p120 antisense phosphorothioate oligonucleotides designed to hybridize with different regions of the p120 sequence were screened on human tumor cell lines in vitro. Marked growth inhibition of HeLa, LOX and HRCC cell lines was found, particularly with antisense p120 oligonucleotide ISIS 3466 in combination with N-[1-(2,3 dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); oligonucleotide ISIS 3466 is complementary to a non-translated region at the 3' end of the molecule. Preliminary in vivo studies on human LOX ascites tumor in nude mice showed marked inhibitory effects on tumor growth by the antisense oligonucleotide ISIS 3466 in the presence of DOTMA when treated on alternate days. PMID- 8476504 TI - Delivery of antisense oligonucleotides by poly(L-lysine) conjugation and liposome encapsulation. PMID- 8476505 TI - Antiviral effect of TNF-alpha and IFN-gamma secreted from a CD8+ influenza virus specific CTL clone. AB - We observed that an influenza-specific cytotoxic T lymphocyte (CTL) clone (B7B7) stimulated with peptide-antigen could produce TNF-alpha and IFN-gamma simultaneously. The culture supernatant containing both TNF-alpha and IFN-gamma of antigen-stimulated CTL clone B7B7 significantly enhanced the lysis of influenza A/PR/8 virus-infected L-M2d6 cells or Meth A cells. Enhanced lysis of influenza virus-infected cells by the supernatants was inhibited by pretreatment of the supernatant with antimurine TNF-alpha antibody and antimurine IFN-gamma antibody. In addition to a single CTL clone, we observed that bulk-cultured CTLs were able to produce TNF and IFN when incubated with target cells. These results suggest that the protective mechanism mediated by TNF-alpha and IFN-gamma secreted from CTL may be possible in the course of an influenza infection. PMID- 8476506 TI - Antibodies to polymerized albumin in woodchuck hepatitis virus infection. AB - Polymerized human serum albumin may play a role in the entry of hepatitis B virus into hepatocytes, and antibodies to polyalbumin that frequently appear during acute hepatitis may aid the process of viral clearance. We developed an enzyme linked immunosorbent assay for antibodies to polymerized woodchuck albumin to enable us to evaluate further the role of these antibodies in an animal model system. Sera from 17 uninfected adult woodchucks and 8 newborns showed no binding to control plates coated with woodchuck transferrin, woodchuck albumin, or polymerized human serum albumin. One of 8 newborn animals demonstrated a significant antibody titer to polymerized woodchuck albumin, and 16 of 17 adults without evidence of prior woodchuck hepatitis virus infection had measurable serum antibody titers. Antibodies to polymerized woodchuck albumin could be adsorbed by prior incubation with the antigen. In 2 animals subjected to experimental infection, significant rises in polyalbumin antibody were seen. When 4 adult woodchucks were immunized with woodchuck polyalbumin, significant increases in antibody titer were observed in 2 of the 4 animals. Of the 4 immunized and 4 controls subsequently challenged with woodchuck hepatitis virus, 7 became viremic and all 8 developed antibody to woodchuck hepatitis virus core antigen. We conclude that naturally occurring antibodies to polymerized woodchuck albumin are observed in most adult woodchucks in the absence of woodchuck hepatitis virus infection and do not seem to confer immunity against infection with this virus. PMID- 8476507 TI - A comparison of human immunodeficiency virus (HIV) seropositivity and hepatitis B surface antigenemia (HBs Ag) among the same group of apparently healthy pregnant women in Lagos, Nigeria: a preliminary report. AB - Two hundred and fifty apparently healthy pregnant women attending the Obstetrics and Gynecology Clinic of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria were screened for a comparison of the prevalence of HIV seropositivity and hepatitis B surface antigenemia (HBs Ag) amongst them. The Karpas AIDS cell test for HIV seropositivity and Bioman Hepatitis test kits were used as described by the manufacturers. HIV seropositive cases were confirmed using the Western blot test. Results revealed that out of the 250 pregnant women screened, 2 (0.8%) and 11 (4.4%) were HIV-1 and HBs Ag seropositive, respectively. However, the same 2 pregnant women now constituting 2 (18.2%) of the 11 HBs Ag positive pregnant women were simultaneously HIV-1 seropositive. Antibody to HIV-2 was not recorded in all HIV seropositive cases. This is the first report on the simultaneous prevalence of HBs Ag and HIV seropositivity among apparently healthy pregnant women in Lagos, Nigeria. PMID- 8476509 TI - Perinatal transmission of hepatitis B virus in Senegal, west Africa. AB - We studied 152 healthy pregnant women and their 156 newborns for markers of hepatitis B virus (HBV) infection in Dakar, Senegal. Of these, 120 mothers (79%) had antibodies to the hepatitis B core antigen (anti-HBc), 21 (13.8%) were hepatitis B surface antigen (HBs Ag) positive, including 2/21 (9.5%) hepatitis B core-associated antigen (HBe Ag) positive and 1/21 (4.7%) HBV DNA positive. At birth, 11 (7%) infants were HBs Ag positive; 9/11 had an HBs Ag positive mother. Ten of these HBs Ag positive-born infants were investigated at 6-7 months: 5 were strongly HBs Ag positive and developed antibodies to HBs Ag, HBc Ag or HBe Ag; these 5 (3.2% of the total) probably became chronic carriers of HBV. The 5 others were HBs Ag negative and 4/5 did not develop antibodies against HBV Ag; HBs Ag positivity at birth was likely due to contamination of the mother's blood. Thirty one of the 145 HBs Ag negative-born infants were studied at 6-7 months and remained HBs Ag negative. However, 5 (16%) showed evidence of HBV infection occurring between 0 and 6 months, as shown by the development of antibodies to HBs Ag, HBc Ag, and/or HBe Ag. Despite the low prevalence of HBV DNA and HBe Ag in HBs Ag positive African mothers, this study shows the occurrence of perinatal transmission of HBV in West Africa, in contrast with previous studies. Perinatal HBV transmission could explain the HBV vaccination failure recently reported in children in Senegal. PMID- 8476508 TI - Diminished influenza A virus-specific MHC class I-restricted cytotoxic T lymphocyte activity among elderly persons. AB - Influenza A virus-specific MHC class I-restricted cytotoxic T lymphocyte (CTL) activities among young and elderly adults were compared. Peripheral blood lymphocytes from 10 young adults, (mean age 27 +/- 2.4 years) and elderly persons (mean age 71 +/- 1.6 years) were stimulated with influenza A/Taiwan/1/86 (H1N1) virus for 7 days and assayed for lytic activity against A/Taiwan, A/Shanghai (H3N2), and B/USSR virus-infected autologous target cells. Young adults exhibited significantly higher influenza A cross-reactive CTL activity against A/H1N1 and A/H3N2 target cells when compared to aged persons. This was true at all effector to-target cell ratios tested. Negligible lysis of B/USSR-infected target cells or nonautologous A/Taiwan-infected cells was observed. The number of leukocytes recovered per milliliter of blood was also significantly higher in young adults than in old donors; however, the percentage of CD45+ (common leukocyte antigen), CD3+ (T cells), CD4+ (T helper), and CD8+ (T cytotoxic/suppressor) as well as the CD4+/CD8+ ratios was similar in both groups. Depletion of cells with monoclonal antibodies indicated that the effector cells were CD8+ T cells. Serum neutralizing antibody (Nt Ab) titers were similar among young and elderly persons and there was no correlation between Nt Ab and CTL activity. These results demonstrate a reduced influenza virus-specific MHC class I-restricted CTL activity among elderly persons. The deficiency in this cell-mediated immune function may contribute to the morbidity and mortality from influenza virus infections in this population. PMID- 8476510 TI - Induction of antihemagglutinin antibodies by polyclonal antiidiotype antibodies. AB - Antiidiotypic antibodies can be envisioned as an alternative approach in the development of vaccines against influenza virus, which exhibits natural antigenic variations. In our work, we obtained two polyclonal cross-reactive anti-Id antibodies against PY102, VM113, and VM202 mAbs, which in turn are specific respectively for PR8 virus and laboratory-induced virus variants (PY102-V1 and VM113-V1). With these cross-reactive anti-Id antibodies, we were able to elicit anti-HA antibodies in mice. In comparing the anti-HA antibody response in animals injected with anti-Id antibodies to those immunized with PR8 influenza virus, we demonstrated that the HI titer was higher after virus immunization and that the PR8 virus boost was more efficient in this group. Our results showed that the polyclonal cross-reactive anti-Id antibodies were more efficient than the individual anti-Ids at eliciting responses. At the same time, we demonstrated that PR8-primed T cells, cultured with B cells from animals immunized with anti Id antibodies, were able to produce anti-PR8 antibodies subsequent to stimulation with influenza virus. PMID- 8476511 TI - Changes in the cytotoxic T-cell repertoire of HIV-1-infected individuals: relationship to disease progression. AB - The repertoire of antigen-specific receptors expressed on T lymphocytes is shaped by fixed genetic and variable environmental selective pressures. Recent technological advances have enabled the analysis of T-cell receptor (TCR) expression in the context of selective pressures arising through normal immune system development and also through pathological features of disease. The pathological features of acquired immune deficiency syndrome (AIDS) are reflected by selective depletion of particular T lymphocyte subsets and expansion of others. An important question concerning the immunopathogenesis of AIDS is whether or not the perturbation of the CD4+ and CD8+ T-cell subsets following infection with human immunodeficiency virus (HIV) is selective based on TCR variable (V) region gene expression. To address this question, we have functionally analyzed TCR V gene expression on CD8+ cytotoxic T lymphocytes from HIV-1-infected individuals. This was done using monoclonal antibodies against individual TCR V regions to trigger redirected cytolysis in 51Cr release assays. The percent specific lysis induced by each antibody functionally measures the representation of the TCR V region gene product it is specific for. Relative to non-HIV-infected controls and asymptomatic HIV-infected individuals with only moderate CD4 lymphocyte depletion, HIV-infected individuals with low CD4 lymphocyte counts exhibited skewed patterns of TCR V region representation. Therefore, the perturbation within the CD8+ cytotoxic T lymphocyte repertoire in HIV infection appears to be selective based on TCR V region usage, increasingly so as disease progresses. The TCR V genes affected varied between different HIV infected individuals and skewing detected in functional assays was not always apparent by flow cytometric analysis. These results suggest that HIV infection causes generalized effects on the T-cell repertoire, which are reflected in the relative TCR V gene representation of the CD8+ cytotoxic T lymphocyte population in peripheral blood. PMID- 8476512 TI - Fractals and foods. AB - Fractal geometry and related concepts have had only a very minor impact on food research. The very few reported food applications deal mainly with the characterization of the contours of agglomerated instant coffee particles, the surface morphology of treated starch particles, the microstructure of casein gels viewed as a product limited diffusion aggregation, and the jagged mechanical signatures of crunchy dry foods. Fractal geometry describes objects having morphological features that are scale invariant. A demonstration of the self similarity of fractal objects can be found in the familiar morphology of cauliflower and broccoli, both foods. Processes regulated by nonlinear dynamics can exhibit a chaotic behavior that has fractal characteristics. Examples are mixing of viscous fluids, turbulence, crystallization, agglomeration, diffusion, and possibly food spoilage. PMID- 8476513 TI - Effect of manufacturing factors, composition, and proteolysis on the functional characteristics of mozzarella cheese. AB - Shredding and melting characteristics are vital to the function of low-moisture Mozzarella cheeses that are used as ingredients for pizza and related foods. Newly manufactured Mozzarella melts to a tough, extremely elastic, and somewhat granular consistency with limited stretch that is unacceptable for pizza. However, during the first few weeks of refrigerated storage, a dramatic transformation occurs as the unmelted cheese becomes softer and the melted cheese becomes more viscous, less elastic, and highly stretchable. Thus, the cheese attains optimal functionality for pizza. Over longer periods, Mozzarella becomes excessively soft and fluid when melted and is no longer acceptable for pizza. Low moisture Mozzarella is correctly viewed as a cheese that requires aging. The functional characteristics of low-moisture Mozzarella are due initially to the chemical composition, including fat, moisture, NaCl, and mineral contents, and the structure of the paracasein curd matrix that is established during manufacture. Changes in functional characteristics during aging are directly related to proteolysis rate and possibly proteolytic specificity. Proteolysis during aging is influenced by manufacturing factors such as starter culture, coagulant, and stretching temperature, and possibly to indigenous proteases in the cheesemilk such as plasmin. PMID- 8476514 TI - [Safe handling of cytostatic agents]. PMID- 8476515 TI - [Nursing documentation: consensus in practice. Introduction]. PMID- 8476516 TI - [Nursing documentation: consensus in practice (1). Its application in stage 1: Mr. De Langen]. PMID- 8476517 TI - [Management of trauma caused by sexual assault and incest]. PMID- 8476518 TI - [The force of our product instead of the power of the hierarchy]. PMID- 8476519 TI - [WIP (Workgroup Infection Prevention), or: campaign against hospital infection. Infection control: knowing is one, doing is two. Interview by Toine de Graaf]. PMID- 8476520 TI - [Careless nursing care]. PMID- 8476521 TI - [Team work in the general psychiatric hospital]. PMID- 8476522 TI - [Medica 93: from high tech to BIG (Professions in Individual Health Care)]. PMID- 8476523 TI - [Pass it in, Pass it on: the nurse as 'Bellringer']. PMID- 8476524 TI - [Nursing documentation: Consensus in practice. Its application in stage 2: Jan]. PMID- 8476526 TI - [The why of nursing diagnosis]. PMID- 8476525 TI - ['Care about your Profession' or: towards greater self-assurance]. PMID- 8476527 TI - [Environment and care (9). Nuisance as a disturbance of health experience]. PMID- 8476528 TI - Acute phase response of rabbit to HgCl2 and CdCl2. AB - A variety of changes occur in the rabbit under metal stress which include the appearance of the acute phase protein, C-reactive protein in the serum and significant reduction in the serum titres of albumin and acetylcholinesterase. The phospholipid profile is positively correlated with the higher degree of tissue necrosis encountered in mercury treated rabbit. Cadmium and mercury treatments evoke a similar response pattern in rabbit differing only in the degree of change. PMID- 8476529 TI - Relationship between asthma and allergic antigens in rural houses. AB - Asthma is one of the most frequent and common diseases in China. It seriously threatens the health of the population. It is evident that mites present in rural houses may serve as an allergic antigen. In our survey, we have found several kinds of mites in farmers' houses in the northeastern part of China which have very close relation with asthmatic diseases. Investigations in rural houses further proved that the cause of asthma is certainly related with the allergic antigen of mites. The methods of prevention and control of mites are enumerated. PMID- 8476530 TI - Estimation of acute toxicity of ammonium sulphate to the fresh water catfish, Heteropneustes fossilis I. Analysis of LC50 values determined by various methods. AB - The acute toxic effects of ammonium sulphate to fresh-water catfish, Heteropneustes fossilis (H. fossilis) have been studied by determining LC50 values with 95% confidence limits, by the graphic method, the logistic method, the Spearman and Karber method and the trimmed Spearman-Karber method. The trimmed Spearman-Karber method was found the most ideal for ammonium salt toxicity test. The flaws in the trimmed Spearman-Karber method are also discussed. PMID- 8476531 TI - Ultrastructural study of moniliformin induced lesions of myocardium in rats and mice. AB - Effects of moniliformin on the ultrastructure of the myocardium of mice and rats were studied. Mice were given moniliformin orally at a dose of 29.46 mg.kg-1 the LD50. One h after dosing, lesions of the mitochondria of the myocardial cells were found which became more severe in 2 and 3 h. Ultrastructural lesions were also observed in the myofibrils and sarcolemma. Rats were given moniliformin orally at the dosage of 6 mg.kg-1 once daily for 56 d. Lesions of mitochondria and myofibrils were relatively mild. In the myocardiac specimens taken from the 21d post-toxin administration, lesions of the sarcolemma became more obvious. These moniliformin-induced lesions were similar to the ultrastructural changes in the myocardium of patients with Keshan disease. Our findings indicate that there may be a close and important relationship between moniliformin intoxication and Keshan disease. PMID- 8476532 TI - Estimation of acute toxicity of ammonium sulphate to the fresh-water catfish, Heteropneustes fossilis. II. A histopathological analysis of the epidermis. AB - The toxicity of 4000 ppm (96 h LC50 value) of the inorganic fertilizer ammonium sulphate on the epidermis of Heteropneustes fossilis (H. fossilis) at different intervals of time has been studied. The destruction induced by the ammonium salt is massive. Secretion of a copious amount of slime from the goblet mucous cells leading to the exhaustion and/or shedding and subsequent disappearance is perhaps the first reaction to the toxicity of the irritant. Later, the polygonal epithelial cells of the outermost layer show cyclic stages of necrosis and sloughing followed by their regeneration and repair. The contents of the club cells show enormous shrinkage and condensation with subsequent replacement of their areas with a hazy substance. In the earlier stages of exposure, regeneration takes place quickly, side by side with the degenerative changes at different stages of experimentation. Later after 8 to 10 d, the degenerative changes slow down and the epidermis appears identical to that of the normal skin. Goblet mucous cells also showed several cyclic increases followed by decreases in number and activity. PMID- 8476533 TI - Tissue distribution of [3H]-nicotine in rats. AB - This study was conducted in adult male Sprague--Dawley rats to determine the distribution of [3H]-nicotine in blood and tissues following a bolus injection and a constant infusion of pure nicotine. The animals were anesthetized and injected with either 0.5 ml of nicotine solution or given a constant infusion of the same nicotine solution with identical amounts of radioactive nicotine. After sacrifice, blood, brain, trachea, salivary gland, esophagus, lung, heart, liver, fundus, antrum, spleen, pancreas, duodenum, jejunum, ileum, cecum, colon, kidneys, adrenal gland, and testes were collected and measured for radioactivity by scintillation counting. The distribution of nicotine was found highest in kidneys by both routes of administration. Higher accumulations were also found in salivary and adrenal glands, fundus, antrum, duodenum, jejunum, ileum and colon. Retention of nicotine via constant infusion was significantly higher in esophagus, fundus antrum, spleen, cecum, pancreas, testes, heart and muscle when compared with bolus injection. Six-fold increase in retention of blood levels of nicotine were found with constant infusion. (P < 0.05). The results indicate that longer retention of nicotine occurs in blood and other specific tissues such as esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle via constant exposure. These data may implicate the predisposition of these tissues to pathologic manifestations. PMID- 8476534 TI - Human toxicosis caused by moldy rice contaminated with fusarium and T-2 toxin. AB - This is the first report on human toxicosis in China caused by moldy rice contaminated with Fusarium and T-2 toxin due to heavy rainfall during rice harvest season. One hundred and sixty-five persons ate the moldy rice and ninety seven persons fall ill of food poisoning. The incidence was 58.8% and latent period was 10-30 min. The chief symptoms were nausea, dizziness, vomiting, chills, abdominal distension, abdominal pain, thoracic stuffiness and diarrhea. The fungi isolated from the moldy rice were predominantly Fusarium heterosporum (F. heterosporum) and F. graminearum. T-2 toxin was found in these moldy rice and the highest level was 420 ppb. The chief causative agent of intoxication was T-2 toxin. PMID- 8476535 TI - Non-genotoxic carcinogens. Approaches to their risk assessment. AB - Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment. In turn, chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms. There were described in literature several simple, rapid and inexpensive short term tests to reasonably predict the genotoxic nature of chemicals but in contrast, there is no reliable test or battery of tests available to predict the carcinogenicity of non genotoxic compounds and this poses a major problem to their risk assessment. In addition, there are conflictive opinions about risk assessment needs for both classes of carcinogens. Some workers believe that for non-genotoxic carcinogens, thresholds for exposure can be drawn while others do not. In this review, the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs. PMID- 8476536 TI - Effects of intermediate metabolites of 37 xenobiotics on the catalytic activities of reconstituted cytochrome P-450IIB1 and P-450IA1 enzyme systems. AB - Direct effects of intermediate metabolites of 37 different xenobiotics on the catalytic activities of both reconstituted cytochrome P-450IIB1 and P-450IA1 enzyme systems were studied by determination of NADPH oxidation at various intervals after initiation of the reaction. The results showed that cytochrome P 450IIB1 isozyme was much more likely than cytochrome P-450IA1 isozyme to be attacked by the reactive intermediates formed by some xenobiotics with smaller molecular weight and lose its catalytic activities. These xenobiotics were carbon tetrachloride, chloroform, carbon disulfide, benzene, parathion, methylparathion, methyldursban and dimethylnitrosamine. In contrast, however, steadily increasing metabolic activities were observed towards benzo(a)pyrene, 3-methylcholanthrene and polychlorinated biphenyls in reconstituted cytochrome P-450IA1 enzyme system as the reaction time prolonged within 4 min. The method discussed in this paper could be used as a simple and convenient way to observe directly the autocatalytic destruction of P-450 enzymes by some chemical agents. PMID- 8476537 TI - Feeding supplemental iodine to adult mink; effect on thyroid hormones in adult and offspring. AB - We fed adult mink diets containing supplemental iodine, from 0 to 320 ppm, for one or seven months prior to breeding. Blood samples collected from the adults and their offspring (kits) at 4 wk post-partum were assayed for total thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and T4-binding indices. As expected T4 concentrations of the adult and kit mink varied inversely with the level of supplemental iodine. In addition, T3 and rT3 concentrations decreased gradually in kits from the long-term experiment in response to the increased dietary iodine of the dams. T3 concentrations of kits from dams fed iodine short term decreased markedly while rT3 concentrations were elevated greatly in response to increased dietary iodine of the dam. These decreases in hormone levels are due to serum iodine blocking the thyroid uptake of iodine and subsequent decrease of hormone synthesis. Excess iodine may also block the effect of thyroid stimulating hormone. The T4-binding indices of the adults, in general, were depressed, while the T4-binding indices of the kits were more variable. These effects are probably due to fluctuations in thyroglobulin. PMID- 8476538 TI - Effect of pesticides on growth of rhizobia and their host plants during symbiosis. AB - Effect of various pesticides (insecticides, fungicides and herbicides) has been studied on growth and efficiency of symbiotic properties of 3 fast growing Rhizobium sp. under green house conditions. The results revealed adverse effects on plant growth and nitrogen fixing capacity as measured by dry weight and total nitrogen content of plants infected with pesticide treated Rhizobium. Of the pesticides tested, herbicides were found to be more effective on the above parameters than the insecticides and fungicides. PMID- 8476539 TI - Relative abundance and the relationships between aniline, phenol and catechol degraders in fresh water. AB - Relative abundance and relationships between aniline, phenol and catechol degraders were investigated in unpolluted and polluted fresh waters in Osaka prefecture, Japan. Phenol and catechol degraders were found more frequently compared to aniline degraders. The results indicate that these degraders were more abundant in polluted waters than in unpolluted waters. Aniline degraders isolated from the Ina River water showed a higher capability of degrading catechol than phenol. Analysis on sequence homology among these three kinds of degraders indicated a possible relationship between aniline degraders and certain strains of both catechol and phenol degraders. PMID- 8476540 TI - Collateral axons of cholinergic pontine neurones projecting to midline, mediodorsal and parafascicular thalamic nuclei in the rat. AB - The organization of collateral axons projecting from neurones in the pontine laterodorsal tegmental nucleus (LDTg) has been examined using combinations of retrograde neuronal tracers with immunocytochemical markers for the acetylcholine synthesizing enzyme choline acetyltransferase (CHAT), focussing on projections to the midline, mediodorsal and parafascicular thalamic nuclei and the ventral tegmental area. 25-59% of LDTg neurones projecting to the mediodorsal nucleus provided collaterals to the midline nuclei. Virtually all (87-96%) of these double retrogradely labelled neurones appeared cholinergic. 9-18% of LDTg neurones projecting to the parafascicular nuclei also provided a collateral to the midline nuclei and 50-78% of these double retrogradely labelled neurones stained for CHAT. 26-29% of the single LDTg neurones which projected collaterals to both the mediodorsal and midline nuclei, were found to project a third collateral to the ventral tegmental area. These anatomical findings, taken together with functional evidence, suggest that cholinergic terminals arising from LDTg are involved in coordinating thalamic mechanisms of brain state control; and in regulating dopaminergic pathways, both directly and via the thalamus. PMID- 8476541 TI - Differential organization of synapses immunoreactive to phenylethanolamine-N methyltransferase or neuropeptide Y in the parvicellular compartments of the hypothalamic paraventricular nucleus of the rat. AB - The parvicellular compartments of the paraventricular nucleus of the hypothalamus (pPVN) contains particularly high concentrations of neuropeptide (NPY)-containing fibres of two main cellular origins including (i) neurons of the medulla oblongata, most of which co-store phenylethanolamine-N-methyltransferase (PNMT), the enzyme characterizing adrenergic neurons, and (ii) non-catecholaminergic neurons of the mediobasal hypothalamus. The aim of the present study is to compare the fine organization of the two types of axons terminating in the pPVN. Immunocytochemistry at light and electron microscope levels was used to study both the density and the ultrastructural organization of NPY- and PNMT immunoreactive fibres in the pPVN of animals bearing surgical lesions disrupting axonal pathways from the hindbrain or from the sublying mediobasal hypothalamus. The brainstem knife-cut induced a strong decrease (65%) in the numerical density of PNMT fibres innervating the pPVN, but was without significant effects on the density of NPY fibres. On the other hand, the hypothalamic knife-cut induced an 80% decrease in the density of NPY fibres within the PVN without affecting the number of PNMT fibres. The electron microscope study showed that in the control pPVN contralateral to the lesions, the majority (64%) of PNMT synapses were asymmetric axo-dendritic synapses, whereas the majority (67%) of NPY synapses form symmetric contacts with both dendrites and perikarya of the hypothalamic nucleus. By contrast, after a hypothalamic knife-cut, the majority (66%) of NPY synapses identified in the pPVN exhibited features of asymmetric synapses. These data indicate that the large majority of NPY-immunoreactive fibres detected within the pPVN arise from non-catecholaminergic neurons located in the mediobasal hypothalamus and mainly form symmetric synapses on neurons of the pPVN, whereas only a minority of them arise from hindbrain regions, and like PNMT fibres innervating this nucleus preferentially form asymmetric axo-dendritic synapses. PMID- 8476542 TI - Neuropeptides in the human celiac/superior mesenteric ganglionic complex: an immunohistochemical study. AB - The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), galanin (GAL) and enkephalins (ENK) is studied in the human celiac/superior mesenteric ganglionic complex of pre- and full-term newborns, and adult subjects by means of immunohistochemistry. The antisera used labelled nerve fibres and terminal-like networks for each examined peptide, as well as VIP- and SOM-positive postganglionic neurons. Differences in the relative amount and density of the structures immunoreactive to the various peptides were observed. Moreover, variations in the amount and type of labelled elements were appreciable for each peptide when specimens from subjects at perinatal and adult ages were compared. Double-labelling immunofluorescence for SP and each other peptide showed that co-localization with SP is very frequent for CGRP, moderate to scarce for GAL and SOM, and rare to absent for PHI, VIP and ENK. VIP-, ENK- and CGRP immunolabeled perikarya bearing the morphological features of the small intensely fluorescent (SIF) cells occurred in the organ. The presence of a paraganglion in one of the specimens examined allowed the detection of VIP- and ENK-positive cell bodies and VIP-, ENK-, SP- and GAL-like immunoreactive varicose nerve fibres in it. The results obtained provide substantial morphological data in support of the involvement of the examined peptides in the chemical interneuronal signalling in the human celiac/superior mesenteric ganglia. PMID- 8476544 TI - Primary care (another view) PMID- 8476543 TI - Allocating health care resources. The vexing case of rehabilitation. AB - The allocation of resources to rehabilitation is beset with many difficulties. Among them are the general crisis in the American health care system and the problem of how to make a case for the role of rehabilitation. Rehabilitation must be prepared to show how and why it is a good medical and social investment in relation to other needs. Rehabilitation has played a secondary role in the American health care system because of overemphasis on curative and life extending medicine. Rehabilitation must work to show that money invested in caring is as well spent as money aiming at the extension of life. It must also establish a fresh new vision of health care in general as well as illustrate where rehabilitation stands in a more integrated and coherent health care system. Improved quality of life, which rehabilitation can provide, is as important as saving and extending life. PMID- 8476545 TI - Physical medicine and rehabilitation. Trends in academic productivity. AB - Numerous authorities have emphasized the need for expanding the quantity and quality of physical medicine and rehabilitation (PM&R) research and academic productivity. Thus far, however, attempts to evaluate academic productivity have involved the manual sampling of relevant specialty journals. This approach greatly underestimates productivity. By conducting a computer-facilitated search for PM&R-related publications and then contacting the most academically prolific PM&R departments to verify the computer-generated data, it was found that computer search strategies more accurately estimate PM&R academic productivity. PM&R publication activity increased by 15% in the United States and 46% internationally over the period 1988 to 1990. At least 76% of the United States residency programs in PM&R had scientific publications over this period. With ever increasing emphasis placed on academic productivity, the trend of increasing productivity can only be expected to continue in the future. PMID- 8476546 TI - Geriatrics training in physical medicine and rehabilitation. AB - A survey was conducted to determine the level of training in geriatrics in physical medicine and rehabilitation (PM&R) residency training programs. Questionnaires were sent to 76 accredited programs in 1989 with a 63% (48/76) response rate. Results show that 49% of patients cared for by PM&R residents in inpatient settings are 65 years of age or older, and 42% of patients cared for in ambulatory settings are in the same age group. Of PM&R programs, 30% have physician faculty who are geriatric "specialists." PM&R residents have a significant exposure to elderly patients in the consultation role. Less exposure to elderly patients occurs in distinct geriatric rehabilitation and geriatric medicine programs or units. Among 10 medical specialties, PM&R programs compare well in terms of teaching about the topics and the personnel that are important in geriatrics. This is due in part to an obvious overlap between the content of rehabilitation medicine and that of geriatrics. Furthermore, there is moderate interest in PM&R in developing fellowship training in geriatric rehabilitation. The need for more academic faculty who are geriatric "specialists," as well as the need for increasing PM&R exposure to distinctly geriatric settings as a part of training, is apparent. PMID- 8476547 TI - Segmental v dermatomal somatosensory-evoked potentials. Normal intertrial variation and side-to-side comparison. AB - Although segmental and dermatomal somatosensory evoked potentials have been used in the diagnosis of lumbosacral radiculopathy, the unilateral or bilateral normal intertrial variation of these responses has not been investigated. Furthermore, there exists little consensus on how many sequential trials for a single nerve or dermatome are optimal and how to use the data generated from these trials. Without investigation of these basic parameters, determination of what constitutes a normal somatosensory-evoked potential (SEP) is difficult. In 29 normal subjects, the ipsilateral intertrial variations, arithmetic mean side-to side differences and maximum potential side-to-side differences with stimulation of the superficial peroneal sensory nerve, sural nerve and L5 and S1 dermatomes with respect to P1 and N1 latencies and peak-to-peak amplitudes were investigated. Considerable ipsilateral intertrial variation was observed and side to-side comparisons revealed a further increase in this inherent variation regarding the above measured parameters. The maximum potential side-to-side differences were even more remarkable than the mean side-to-side differences. For these results and others presented, a method of evaluating SEP parameters whereby the arithmetic mean of two sequential trials for both latency and amplitude is presented that attempts to minimize the normal, inherent variation. We also suggest an additional parameter with which to evaluate SEPs: the maximum side-to side latency difference. Only through the use of a consistent methodology can segmental or dermatomal SEPs be utilized in a reliable diagnostic manner. PMID- 8476548 TI - Performance profiles of the functional independence measure. AB - The functional independence measure (FIM) is used to determine the degree of disability that patients experience and the progress that they make through programs of medical rehabilitation. Rasch analysis is a statistical technique for constructing interval measures from ordinal data that was applied to derive FIM measures. The major factors that are taken into account to produce FIM measures are the relative difficulty in performance of FIM items and the ability of the persons tested. Our analyses showed the relative difficulties that patients experienced in performing items in the FIM. There were two dominant patterns of difficulty, one for motor FIM items and the other for cognitive FIM items. The patterns were consistent across impairment groups, although not identical. Of the motor items, eating and grooming were easiest whereas stair climbing, tub/shower transfers and locomotion were most difficult. Of the cognitive items, expression and comprehension were easiest and problem solving was the most difficult. The patterns of difficulty in performing FIM items are illustrated by analysis of the following impairment groups: for motor items, orthopedic conditions, stroke with left hemiparesis and spinal cord dysfunction; for cognitive items, orthopedic conditions, brain dysfunction, stroke with right hemiparesis and spinal cord dysfunction. By understanding patterns of difficulty in performing FIM items according to types of impairment and levels of function, clinicians may more precisely design treatment programs, use services and predict outcomes of medical rehabilitation. PMID- 8476550 TI - Drug-induced dystonia in a patient with C4 quadriplegia. Case report. AB - Prochlorperazine, a piperazine phenothiazine, is a commonly used anti-emetic that blocks dopamine receptors in the central nervous system. Prochlorperazine causes various extrapyramidal syndromes, with the incidence in the inpatient population estimated to be 0.5 to 0.8%. These side effects are typically manifested by motor dysfunction and easily observed on physical examination. We report the case of an 18-year-old male with C4 complete quadriplegia who developed an acute dystonic reaction isolated to the tongue during short-term treatment with prochlorperazine. This case demonstrates the importance of maintaining a high level of suspicion in the spinal cord population, considering that many key physical findings may be absent below the level of function. PMID- 8476549 TI - Rehabilitation medicine consultation in persons hospitalized with AIDS. An analysis of thirty cases. AB - This retrospective study outlines interventions taken as a result of rehabilitation medicine consultation in persons hospitalized with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The medical records of 30 persons with HIV infection consecutively referred for rehabilitation medicine consultation over a one-year period were reviewed. The sample was composed primarily of white, homosexual males with a mean age of 38.5 (SD, 8.5) years and a mean length of AIDS diagnosis of 14.6 (SD, 14.1) months. Rehabilitation medicine evaluation resulted in additional diagnoses in four cases (13.3%), prescriptions for new medications in 8 (26.7%), physical modalities/devices in 9 (30.0%) and referrals to occupational, physical and speech therapies in 26 (86.7%), 24 (80.0%) and 3 (10.0%) patients, respectively. Interventions were often directed toward deconditioning, painful peripheral neuropathy and fatigue. Mean survival after rehabilitation consultation was approximately 23 weeks. No intervention was novel or unusual suggesting that current knowledge is sufficient to manage much of the disability associated with HIV infection. This study concludes that rehabilitation medicine can contribute to the management of persons hospitalized with AIDS. Further research should address efficacy of intervention, fatigue as a source of disability and the value of early rehabilitation intervention. PMID- 8476552 TI - Regulatory aspects of modified release dosage forms: in vivo/in vitro correlations. PMID- 8476551 TI - Physiologic considerations in the determination of optimum interelectrode distance for the antidromic recording of compound sensory nerve action potentials. Commentary. PMID- 8476553 TI - [Microbiological validation of a film system for monitoring total aerobic bacteria on surfaces and laboratory garments in controlled areas]. AB - The microbiological control of the environment is a real issue inside the pharmaceutical production plants. Actually the most used methods are the Contact Plates and the Swabs. The purpose of this study is to evaluate the performance of a new "ready to use" method called Petrifilm SM (produced by 3M Laboratories). Petrifilm consists of a dry-rehydratable growth medium coated on a flexible film. Petrifilm is tested in comparison with Swabs and Contact Plates to monitor the microbiological pollution on labs surfaces and operator's overalls. The results obtained are comparable with the above mentioned methods, but with important advantages being less bulky, considerably time saving and highly reproducible. Hence, we think that Petrifilm S, can be successfully used instead of the other two more traditional methods. PMID- 8476555 TI - [The use of transgenic animals in the evaluation of the genotoxic properties of compost chemicals]. PMID- 8476554 TI - X-ray fluorescence determination of bromine traces in pharmaceutical formulations containing sodium diclofenac. AB - The X-ray fluorescence spectroscopy (XRF) on solid samples is applied to the organic bromine impurities assay on pharmaceutical formulations of sodium diclofenac (DCF). A wide range of Br contents (7-1564 ppm) in the tablets is obtained, depending on manufacturer source and batch preparation. As the impurities concern only the sodium diclofenac employed, and the presence of Br might be a toxicity index arising from the synthetic procedure, the assay of each DCF batch is suggested. PMID- 8476556 TI - [Biopharmaceutics and pharmacokinetics. 5. Distribution]. PMID- 8476557 TI - HLA and I. PMID- 8476558 TI - Defensins: antimicrobial and cytotoxic peptides of mammalian cells. AB - Defensins are antimicrobial and cytotoxic peptides that contain 29-35 amino acid residues, including six invariant cysteines whose intramolecular disulfide bonds cyclize and stabilize them in a complexly folded, triple-stranded beta-sheet configuration. Generated by the proteolytic processing of 93-95 amino acid precursor peptides, the constitute > 5% of the total cellular protein in human and rabbit neutrophils (polymorphonucleated neutrophils--PMN) and are also produced by rabbit lung macrophages and by mouse and rabbit small intestinal Paneth cells. Despite their prominence in rat PMN, defensins are not found in murine PMN. The antimicrobial spectrum of defensins includes gram positive and gram negative bacteria, mycobacteria, T. pallidum, many fungi, and some enveloped viruses. Defensins exert nonspecific cytotoxic activity against a wide range of normal and malignant targets, including cells resistant to TNF-alpha and NK cytolytic factor. They appear to kill mammalian target cells and microorganisms by a common mechanism, which involves initial electrostatic interactions with negatively charged target cell surface molecules (likely the head groups of polar membrane lipids), followed by insertion into the cell membranes which they permeabilize, forming voltage-regulated channels. In addition to their antimicrobial and cytotoxic properties, some defensins act as opsonins, while others inhibit protein kinase C, bind specifically to the ACTH receptor and block steroidogenesis or act as selective chemoattractants for monocytes. Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation, and cytotoxicity may be considerable for humans, even though it is unlikely to be revealed by experimentation with mice. PMID- 8476559 TI - Immunity to intracellular bacteria. AB - Intracellular bacteria are endowed with the capacity to survive and replicate inside mononuclear phagocytes (MP) and, sometimes, within certain other host cells. MP are potent effectors cells that are able to engulf and kill many bacterial invaders. Therefore, intracellular bacteria had to exploit potent evasion mechanisms that allow their survival in this hostile environment. At the early phase, natural killer cells activate antibacterial defense mechanisms. During intracellular persistence, microbial proteins are processed and presented, thus initiating T cell activation. By secreting interleukins, CD4 alpha/beta TH1 cells activate MP, converting them from a habitat to a potent effector cell; TH2 dependent activities seem to be of minor importance. Cytolytic CD8 T cells represent a further element of protection. In the case of Listeria monocytogenes, the gene products responsible for virulence and for the introduction of antigens into the MHC class I pathway are being characterized. Increasing evidence points to a role of gamma/delta T lymphocytes in antibacterial immunity, although their precise function remains to be elucidated. Protection in the host is a local event focussed on granulomatous lesions. MP accumulate at the site of microbial growth and become activated through the CD4 T cell-interleukin-MP axis. Lysis of incapacitated MP and other host cells by CD8 T cells allows release and subsequent uptake by more efficient phagocytes, thus contributing to host protection. At the same time, lysis of host cells promotes microbial dissemination and causes tissue injury, which represent pathogenic aspects of the same mechanism. Research on the immune response against intracellular bacteria not only helps us to better understand how the immune system deals with "viable antigens" in constant trans-mutation, it also forms the basis for the rational design of control measures for major health problems. PMID- 8476560 TI - Peptides naturally presented by MHC class I molecules. AB - MHC class I molecules are peptide receptors of stringent specificity which however still allow millions of different ligands. This is achieved by the following specificity characteristics summarized as allele specific peptide motifs: Peptides are of defined length, depending on the class I allele (either 8 or 9 residues; exceptions have been observed). Typically, 2 of the 8 or 9 positions are anchors that can only be occupied by a single amino acid residue, or by residues with closely related side chains. Location and characteristics of anchors vary with class I alleles. The C terminus of the peptide ligands is frequently an aliphatic or charged residue. Such allele-specific class I peptide ligand motifs, known so far for H-2Kd, Kb, Kk, Kkm1, Db, HLA-A*0201, A*0205, and B*2705, are useful to predict natural T cell epitopes. The latter can be determined by extraction from cells recognized by the T cell of interest. It is not known how the class I ligands are produced in the cell, although speculative models exist. The peptide specificity of class I molecules and experimental evidence indicate that T cells are tolerant to only a small fraction of the expressed genomic sequences and are not tolerant to the remainder. The function of class I molecules is to present a collection of self-peptide samples at the cell surface for surveillance by T cells. PMID- 8476561 TI - The IL-2 receptor complex: its structure, function, and target genes. AB - Proliferation of T lymphocytes is triggered by the interaction of IL-2 with its specific receptor following T lymphocyte activation. The receptor for IL-2 consists of at least three distinct subunits, the alpha chain (IL-2R alpha), the beta chain (IL-2R beta), and the gamma chain (IL-2R gamma). Although the role of IL-2R gamma in IL-2 signalling remains unclear, IL-2R beta is the subunit critical for receptor-mediated signalling. Because IL-2R beta lacks any apparent catalytic motifs, IL-2R beta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2R beta have revealed that at least two distinct cytoplasmic regions of IL-2R beta are involved in IL-2 induced cellular signalling. The "serine-rich" region of IL-2R beta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2R beta mutant cDNAs lacking a particular cytoplasmic region or regions were expressed in an IL-3-dependent mouse pro-B cell line (BAF B03). Meanwhile, another cytoplasmic region of IL-2R beta, the "acidic" region, is responsible for its physical association with an src-family protein tyrosine kinase (PTK), p56lck and is critical for activating the p56lck PTK following IL-2 stimulation. It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction. One pathway is linked to tyrosine phosphorylation events, mediated by a src family protein tyrosine kinase (PTK), and that pathway leads to the induction of the c-fos, c-jun, and other genes of this family. Another pathway leads to c-myc gene induction by an as yet unknown mechanism. We discuss the complex signalling machinery that links the cell surface receptor to the nuclear events. PMID- 8476562 TI - The molecular descent of the major histocompatibility complex. AB - In the last few years, more than 500 primate major histocompatibility complex (Mhc) genes or parts thereof have been sequenced. The extraordinary sequence information is used here to draw conclusions about the manner of Mhc evolution. The Mhc genes are found to evolve at a relatively slow rate with the regularity of a clock. It takes from 1 to 6 million years for a new mutation to be incorporated into an Mhc allele, and the mutation rate is comparable to that of most other primate genes. The nonsynonymous sites coding for the peptide-binding region (PBR) are under relatively weak positive selection pressure (selection coefficient of a few percent only); the nonsynonymous non-PBR sites are under moderate negative selection pressure. The positive pressure is probably provided by parasites and is responsible for the trans-species persistence of allelic lineages at functional Mhc loci for more than 40 million years. PMID- 8476563 TI - Differential regulation of murine T lymphocyte subsets. AB - Signaling pathways in T lymphocytes have been incompletely characterized. It is evident that differences exist among the T cell subsets. We have defined several distinct mechanisms that affect differentially the activities of murine T lymphocyte clones representing various CD4+ and CD8+ subsets: Interferon-gamma (IFN-gamma) inhibits proliferation of but not lymphokine production by TH2 cells. IL-10 inhibits antigen-presenting cell (APC)-induced lymphokine production by TH1 cells but not by TH2 cells. Murine TH1 and TH2 clones proliferate optimally in response to distinct APC populations. TH1 and TH2 clones utilize different TCR associated signaling pathways. High concentrations of antigen (or anti-TCR mAb) inhibit IL-2-induced proliferation (but not lymphokine production) by TH1 and cytolytic T lymphocyte (CTL) clones only. Exposure of TH1 clones (but not TH2 clones or CD8+ CTL clones) to IL-2 induces unresponsiveness to antigen. TH1 and TH2 clones as well as CD8+ clones can be cytolytic, but not all T cells use the same cytolytic mechanisms. CD4+ clones from some mouse strains are not cytolytic if they do not secrete IFN-gamma. Understanding the mechanisms that differentially regulate the various kinds of T cells, in addition to providing insights into the molecular events associated with activation of those subsets, should facilitate modulation of their activities in vivo, making it possible to influence favorably the outcome of disease processes. PMID- 8476564 TI - Gene therapy of the immune system. AB - Many applications of somatic gene therapy relate to the immune system. Several forms of inherited immunodeficiencies are candidates for treatment by gene transfer. Adenosine deaminase (ADA) deficiency causes a form of severe combined immunodeficiency. Stable gene transfer and expression of human ADA has now been obtained in hematopoietic stem cells of mice and, more recently, in large animals. The human ADA has also been introduced and expressed in the primitive human hematopoietic progenitor cells that initiate long-term bone marrow culture. Clinical trials of gene therapy for ADA deficiency have been initiated. The initial protocols were aimed at the correction of peripheral blood T lymphocytes, but recent strategies are attempting ADA gene transfer into peripheral blood or bone marrow stem cells. Other immunodeficiencies that may soon be amenable to somatic gene therapy include leukocyte adhesion deficiency and chronic granulomatous disease. Gene therapy may also be applied to the treatment of acquired disorders. In theory, the hematopoietic stem cells of a human immunodeficiency virus (HIV)-infected patient could be genetically modified and used to reconstitute an HIV-resistant hematopoietic system. Various strategies are currently being investigated to achieve this "intracellular immunization" against HIV. These include the transfer of genes encoding recombinant soluble CD4 molecules, suicide genes under the control of HIV-inducible promoter, and anti HIV ribozymes. Gene transfer could also be used in the treatment of cancer to increase the immune response of the host, to activate prodrugs specifically in tumors, or to protect normal tissues against the toxicities of conventional treatment. Recent progress in all of these applications of gene therapy is reviewed here. PMID- 8476565 TI - T cell-dependent B cell activation. AB - B cells obtain help from T cells in the antibody response by acting as antigen specific antigen presenting cells. A direct signal through binding of antigen to membrane Ig can enhance B cell antigen presentation and T-dependent B cell activation, but is not required for a productive interaction between a small resting B cell and a differentiated helper T cell. As a result of helper T cell recognition of antigen on the B cell surface, the T cell becomes activated and in turn activates the B cell. T cell help has two components: lymphokines which act as growth and differentiation factors for B cells, and additional signals which require cell contact and enable B cells to respond to lymphokines. Contact help activity is regulated like lymphokine synthesis and secretion. Because contact help activity is retained by fixed, activated helper T cells and plasma membranes prepared from activated T cells, contact help is likely to be owing to new proteins expressed as membrane-bound lymphokines or activation antigens on helper T cells. Once induced, contact help can be delivered to B cells independently of recognition of antigen/class II MHC. A newly identified activation antigen of helper T cells, a ligand for the B cell differentiation antigen, CD40, is a key component of contact help. The roles of other T and B cell membrane molecules in contact help are reviewed. PMID- 8476566 TI - Immunoglobulin class switch recombination. AB - A B lymphocyte that produces the immunoglobulin heavy (H) chain mu may switch to the production of another heavy chain class: gamma, epsilon, or alpha. Since the new heavy chain retains the original variable (V) region, antigenic specificity is maintained. The switch is accompanied by a large deletion of DNA at the heavy chain locus. To explain how this deletion is generated, three models have been proposed: recombination between homologs, unequal sister chromatid exchange, and looping out and deletion. While none of the predicted recombination products of the first two models have been found, both by-products of looping out--inversions and circular DNA--have been isolated. Thus looping out and deletion appears to be the appropriate model to explain the genetic events leading to the immunoglobulin heavy chain class switch. One requirement for switching may be transcription of the constant (C) region to which the cell switches. The switch rearrangement is catalyzed by a switch recombinase, and the isolation of the components of this putative enzyme system is in progress. Although the switch deletion is an accepted fact, the discussion is enlivened by scenarios for switching without DNA rearrangement; such suggestions include processing at the RNA level and trans splicing. PMID- 8476567 TI - The molecular basis of allorecognition. AB - Until recently it was generally assumed that the focus of T cell receptor recognition of allogeneic MHC molecules was the polymorphic regions on the molecule that differed between responder and stimulator. It is now clear that all T cell recognition, including self-tolerance and allorecognition, involves both the MHC molecule and its associated peptide ligand. Polymorphic residues located within the peptide binding groove of the MHC and inaccessible to the T cell receptor can profoundly affect selection and recognition of bound peptides. These peptide differences between histoincompatible individuals greatly amplify the antigenic impact of MHC polymorphism and result in the high frequency of alloreactive cells. Evidence for the role of peptides in allorecognition is reviewed. PMID- 8476568 TI - The biochemistry and cell biology of antigen processing and presentation. AB - T lymphocytes with alpha beta receptors recognize antigen in association with the polymorphic products of the class I and class II loci of the major histocompatibility complex (MHC). This presentation of antigen results from the intracellular generation of protein fragments, and the binding and transport to the cell surface of these peptides in stable association with the MHC class I and class II molecules. Each class of MHC molecule appears specialized for capture of peptides present in a particular intracellular compartment. We describe here the structural basis of peptide-MHC molecule interaction, the differences in biochemical behavior that focus the two classes of MHC molecules on peptides of distinct size and location, and the cell biology of MHC molecule transport, peptide generation, and intracellular movement. The importance of conformational changes accompanying peptide binding that affect subunit stability of MHC molecules, and the relationship between these changes and the handling of proteins by intracellular chaperones, are emphasized as key features in the operation of the class I and class II presentation pathways. PMID- 8476569 TI - Regulation of lymphocyte function by protein phosphorylation. AB - Variations in protein phosphorylation provide the predominant means of enzymatic regulation now known in biological systems, especially in the regulation of signal transduction from cell surface receptors. Analysis of these signaling pathways has proceeded especially rapidly in lymphocytes, in part because these cells can be isolated with relative ease and can in many cases be maintained in vitro for prolonged periods as clonal populations. During the past few years, both biochemical and genetic evidence has been adduced indicating that the antigen receptors of T and B lymphocytes associate functionally with nonreceptor protein tyrosine kinases. Similar data implicate protein tyrosine kinases in signaling from the CD4 and CD8 coreceptors and the beta chain of the IL-2 receptor. Protein serine/threonine kinases and several different phosphatases also participate in the intracellular propagation of antigen receptor-derived signals. Here we review the lymphocyte surface receptors that are believed to act by altering protein phosphorylation, the kinases and phosphatases that are believed to regulate signal transduction in lymphocytes, and the implications of these results for the broader study of cell signaling mechanisms. PMID- 8476570 TI - Immunological memory. AB - The past five or six years has seen a resurgence of interest in immunological memory. Areas in which important advances have been made of late or in which problems in understanding persist are covered here: (i) Selection of virgin B cells for entry into the peripheral pool. (ii) Expression of immunoglobulin isotypes and other markers on memory B cells. (iii) Development of memory B cells as a separate lineage from primary response B cells. (iv) Sites of production of memory B cells. (v) Signals that rescue mutating B cells in germinal centers, forming the basis of affinity selection, and programming further differentiation. (vi) The myriad markers of memory T cells, in particular CD45R isoforms. (vii) Selective migration pathways of memory T cells and its possible molecular basis. (viii) The lifespan of memory cells and factors that influence their long-term survival. The data accumulated during this period which have vastly increased our understanding of memory have at the same time highlighted unresolved problems that could block further progress in the field. The thorny question that we cannot at present answer is: How does a memory cell differ from an activated cell and, in the case of T cells, from an effector cell? The problem bears on the interpretation of any study that sets out to correlate memory phenotype with memory function. Immunologists may have donned an intellectual straitjacket in their search for the memory cell. PMID- 8476571 TI - Origin of murine B cell lineages. AB - Until recently, the hematopoietic stem cells (HSC) that appear early in ontogeny were thought to constitute a homogeneous, self-replenishing population whose developmental potential remains constant throughout the life of the animal. Studies reviewed here, however, demonstrated clear differences in the developmental potential of fetal and adult progenitor populations (including FACS sorted HSC). These studies, which chart the ability of various progenitor sources to reconstitute functionally distinct B cell populations, define three B cell lineages: B-1a cells (CD5 B cells), derived from progenitors that are present in fetal omentum and fetal liver but are largely absent from adult bone marrow; B-1b cells ("sister" population), derived from progenitors that are present in fetal omentum, fetal liver, and also in adult bone marrow; and conventional B cells, whose progenitors are missing from fetal omentum but are found in fetal liver and adult bone marrow. B-1a and B-1b cells share many properties, including self replenishment and feedback regulation of development. These B cell studies, in conjunction with evidence for a similar developmental switch for T cells and erythrocytes, suggest that evolution has created a "layered" immune system in which successive progenitors (HSC) reach predominance during development and give rise to differentiated cells (B, T, etc) responsible for progressively more complex immune functions. PMID- 8476572 TI - Transcriptional regulation of T cell receptor genes. AB - The diverse lineages of the mammalian hematopoietic system including both B and T lymphocytes are derived from a single mesodermal progenitor, the pluripotent bone marrow stem cell. The coordinate transcriptional regulation of sets of lineage specific genes is one of the important molecular mechanisms underlying hematopoietic lineage determination and differentiation. The immunoglobulin and T cell receptor (TCR) genes have been used as model systems to study lineage specific transcriptional regulation during lymphoid development. This review summarizes our current understanding of the regulation of TCR gene expression during thymocyte ontogeny. Expression of each of the TCR genes is controlled by T cell-specific transcriptional enhancers that bind partially overlapping sets of ubiquitous and lymphoid-specific transcription factors. These include members of both the ATF/CREB family of basic-leucine zipper proteins and the Ets protooncogene family, as well as the T cell-specific zinc finger transcription factor, GATA-3, and the T cell-specific high mobility group proteins TCF-1 and TCF-1 alpha/LEF-1. The identification of binding sites for these same transcription factors in a number of additional T cell-specific genes suggests that they may play important roles in the coordinate regulation of gene expression that specifies the development of the T cell lineages. Recent studies of the TCR alpha and gamma genes have suggested that negative regulatory elements of transcriptional silencers may also play an important role in controlling the lineage-specific expression of these genes. On going studies are designed to clarify the role of each of the TCR enhancer binding proteins in regulating T cell development in vivo, to more precisely define the interactions between the TCR enhancer binding proteins, and to elucidate the molecular mechanisms underlying transcriptional silencer activity. PMID- 8476573 TI - The molecular cell biology of interferon-gamma and its receptor. AB - The last ten years have seen an explosive growth in our understanding of IFN gamma. The cloning of the cDNAs for IFN gamma and its receptor have made available large amounts of highly purified recombinant IFN gamma and soluble IFN gamma receptor. In addition, highly specific neutralizing monoclonal antibodies have been generated to both of these proteins. Using these reagents, IFN gamma and the IFN gamma receptor have been characterized on a molecular basis. Structure-function studies carried out on these proteins have identified key molecular regions that are required for biologic activity. Moreover, a great deal is now known concerning the physiologic role that IFN gamma plays in vivo. In this review we focus on the new developments in the areas of IFN gamma biochemistry and biology and pay particular attention to the IFN gamma receptor and three aspects of IFN gamma biology that are of special interest to immunologists: host defense, inflammation, and autoimmunity. PMID- 8476574 TI - The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex. AB - Natural killer cells lyse tumor and virally infected cells in a specific manner that has not been molecularly characterized. Target cell expression of major histocompatibility complex (MHC) class I molecules is correlated with target cell resistance to natural killing. A mechanism to explain this observation is that NK cells may display two types of recognition and activation molecules that have opposing functions when bound to target cell ligands. One type of surface receptor such as the NKR-P1 molecule may activate NK activity whereas the other, represented by the mouse Ly-49 molecule, may engage target cell MHC molecules and inhibit cytotoxicity by transducing "negative" signals. NKR-P1 and Ly-49 are structurally related, and they are encoded by genetically linked loci in a chromosomal region, termed the NK gene complex (NKC), on distal mouse chromosome 6. Target cell susceptibility to natural killing may be dependent upon specific ligand-receptor interaction with these activating or inhibitory NKC-encoded molecules. PMID- 8476575 TI - Gamma/delta cells. AB - Before TCR rearrangements, T cell progenitors are committed not only to the alpha beta and gamma delta T cell lineage but also to various subsets of both lineages. In the mouse, distinct gamma delta T cell subsets can develop in the fetal thymus, the adult thymus, or independently of a thymus, probably in intestinal epithelia. The two subsets that develop in the fetal thymus home to and are maintained throughout adult life in the skin and the mucosa of the uterus, vagina, and tongue. They are monospecific. This unusual restriction in receptor repertoires is the result of severe limitations in the generation of diversity in the fetal progenitors of these subsets and the thymic selection. After birth, one gamma delta T cell subset appears in the blood, spleen, and lymph nodes and one in the intestinal epithelia. The receptor repertoires of these subsets are characterized by the preferential usage of particular V gamma gene segments and extensive junctional diversity. Several murine and human gamma delta T cell clones have been shown to recognize classical MHC class I and class II proteins or MHC class I-like proteins, and in very few cases the presented peptides are known. We suspect that the various murine gamma delta T cell subsets interact with different antigen presenting cells which utilize different antigen presenting proteins and reside in different tissues. The function of gamma delta T cells remains unknown. Preliminary results of experiments with gene knock out mice which lack either alpha beta T cells or gamma delta T cells or both suggest that gamma delta T cells do not function as helper cells in humoral immune responses but may complement alpha beta T cells in the defense against various microorganisms. PMID- 8476576 TI - T cell responses to pre-erythrocytic stages of malaria: role in protection and vaccine development against pre-erythrocytic stages. AB - Malaria remains a leading cause of human morbidity and mortality due to the inability of insecticides and chemotherapy/chemoprophylaxis to eliminate the vectors or disease caused by this protozoan parasite. In an effort to develop new methods of control, vaccines targeted to the various stages of the complex life cycle of Plasmodium have been developed. This review describes recent advances in the elucidation of cell-mediated immune mechanisms directed against sporozoites and liver stages of malaria parasites, their role in protection, and their relation to vaccine development. Recent data on the molecular basis of sporozoite liver cell interaction are presented, and these may provide new approaches for chemoprophylaxis and immunoprophylaxis. We describe the role of the circumsporozoite protein, the major sporozoite surface antigen, in sporozoite movement and as a target of humoral immunity. The recognition of the circumsporozoite protein by human T cells is reviewed with emphasis on cytotoxic T cells and immune resistance against the exo-erythrocytic stage of the parasite. Earlier concepts regarding the polymorphisms of the circumsporozoite protein, the immunological relevance of this polymorphism, and predictions regarding vaccine development are reevaluated on the basis of recent data from different malaria endemic areas. Non-CS sporozoite antigens and liver stage antigens are discussed as potential targets for immune intervention. Recent experimental approaches such as multiple antigen peptides, recombinant live vectors, and new more potent adjuvants are considered for the development of more effective malaria vaccine formulations. PMID- 8476577 TI - Endothelial-leukocyte adhesion molecules. AB - One decade ago, vascular endothelium was commonly considered a "non-stick" lining of blood vessels that functioned only to prevent blood coagulation and to separate the vascular space from tissues. By comparison to many other cell types, endothelial cells were thought to be less active, less complex, and less interesting. Since that time, research concerning the endothelium has expanded dramatically and produced a new image of the vascular lining as an active participant in a wide variety of pathophysiological processes, including inflammation and immunity. Nowhere has the excitement been more intense than in the study of the molecular mechanisms of leukocyte adhesion to endothelium. Recent efforts resulted in the identification, characterization, and cloning of multiple endothelial cell-surface glycoproteins that support adhesion through an interaction with specific ligands (or counter-receptors) on leukocytes. The selectins, two of which are found on endothelium and one on leukocytes, support adhesion through the recognition of carbohydrates. Endothelial members of the immunoglobulin superfamily including ICAM-1 and VCAM-1/INCAM-110 bind to leukocyte cell-surface integrins. In various combinations, these and other molecules support leukocyte adhesion to the vessel wall and extravasation, key steps in our response to infection and tissue injury. PMID- 8476578 TI - The role of autoantibodies in autoimmune disease. AB - In autoimmune diseases, autoantibodies may be the actual pathogenetic agents of the disease, the secondary consequences of tissue damage, or the harmless footprints of an etiologic agent. Establishing a pathogenetic role for autoantibodies requires that they meet stringent criteria. It appears that the location of the presumptive target antigen most critically influences the pathogenetic potential of autoantibodies. Autoantibodies directed against cell surface targets, such as hormone receptors, are clearly pathogenetic; those directed against extracellular targets, such as circulating molecules or extracellular matrix, may or may not cause any damage. Those apparently directed against intracellular targets are usually not pathogenetic unless it can be clearly demonstrated (a) that the antigen is released from within the cell so that it can bind onto a cell surface receptor or other extracellular location, such as proteinase 3; (b) that the antigen moves to an aberrant site on the cell surface, such as, perhaps, the small ribonucleoprotein antigen Ro; or (c) that a cross-reactive molecule, the actual target, such as the membrane ribosomal P-like protein, is at an accessible location. PMID- 8476579 TI - Effectiveness and safety of ofloxacin in chronic otitis media and chronic sinusitis in adult outpatients. AB - A multicentric study was conducted to evaluate the clinical efficacy and tolerance of ofloxacin in the treatment of chronic sinusitis and chronic otitis (CSOM) in outpatients. Two hundred milligrams of ofloxacin was administered twice a day orally for 12 days in 198 patients with chronic sinusitis and 215 patients with CSOM. Cultures for bacteriology were carried out before treatment. The spectrum of pathogens sensitive to ofloxacin included Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis and Haemophilus influenzae. Higher concentrations of ofloxacin were obtained at sites of infection than in serum. Favorable results were achieved clinically in 93.7% of chronic sinusitis cases and 93.9% of CSOM cases. Adverse effects occurred in only 4.1% of cases. These results support the use of ofloxacin as the drug of first choice in the treatment of chronic sinusitis and CSOM in adult outpatients. PMID- 8476580 TI - Granulation tissue concentrations of ofloxacin after oral administration in invasive external otitis. AB - Following the fourth dose of 400 mg orally administered ofloxacin, simultaneous external ear canal granulation tissue and serum ofloxacin concentrations were estimated in 15 patients with invasive external otitis. The granulation tissue concentration was 2.2 (range 1.17-4.34) times higher than the serum concentration and 3.73 (range 1.95-11.00) times higher than the MIC90 of ofloxacin against Pseudomonas aeruginosa. PMID- 8476581 TI - Clinical experiences with ofloxacin sequential therapy in chronic ear infections. AB - Quinolones are the drugs of first choice in therapy of chronic ear infections with multiresistant bacteria, especially because of their efficacy against various Pseudomonas species and their lack of ototoxicity. According to clinical experience, best results can be obtained after application of the sequential treatment schedule. To verify this, 61 patients with acute exacerbations of chronic ear infections were treated sequentially with ofloxacin. After a single dose of 400 mg ofloxacin intravenously, the treatment was continued orally with 400 mg once a day over 7 days. Microbiological and serological examination was performed just prior to and 1 week after treatment. Predominant bacteria isolated from the patients' ears were Pseudomonas aeruginosa, Staphylococcus aureus, Proteus spp. and Enterobacteriaceae spp. Following treatment, infections were cured in 23% of cases and 59% showed improvement. Eighteen percent of the cases were persistent, mainly due to epitympanic chronic otitis media, which was an indication for surgical intervention. In general, sequential therapy with ofloxacin revealed encouraging clinical results based on improved patient compliance with the treatment schedule recommended. PMID- 8476582 TI - Antibiotic treatment of sinusitis in general practice. A double-blind study comparing ofloxacin and erythromycin. AB - The present study compared ofloxacin and erythromycin in a double-blind study with parallel groups for clinical efficacy and the number and severity of adverse reactions in patients treated in general practice for acute or chronic sinusitis. All patients lived in medium-sized to large towns and rural districts in the northern and western parts of Sealand, Funen and eastern Jutland, Denmark. Three hundred and nineteen patients were enrolled in the study, of whom 280 were clinically evaluable. From this total number, 136 patients were treated with ofloxacin (31 males and 105 females) and 144 patients were treated with erythromycin (40 males and 104 females). Following administration of either ofloxacin 400 mg once daily or erythromycin 500 mg twice daily for 7-14 days, 94.9% of the ofloxacin-treated group and 94.4% of the erythromycin-treated group were cured of their infections. There was no difference in clinical efficacy. Complications occurred in 18 of 155 patients in the ofloxacin-treated group and 32 of 164 in the erythromycin-treated group (P < 0.05), corresponding to 27 and 45 symptoms respectively (P < 0.01). This difference in adverse reactions principally involved gastrointestinal symptoms, i.e. 19 in the ofloxacin-treated group and 41 in the erythromycin-treated group (P < 0.01). Present findings show that the two antibiotics are comparable as to clinical efficacy, but the frequency of adverse reactions is significantly higher in the erythromycin treated group due to the greater incidence of gastrointestinal adverse reactions. PMID- 8476583 TI - The microbiology of acute and chronic sinusitis and otitis media:a review. AB - There exists no real controversy about the role of aerobic bacteria in acute sinusitis and in acute otitis media. The "infernal trio" Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are by far the most common pathogens in these acute infections. On the contrary, there is still much debate about the normal flora of the paranasal sinuses and the middle ear, although there are some reports of the presence of anaerobes and aerobes in the majority of the normal paranasal sinuses. In chronic sinusitis bacteriological cultures show a greater variation than those in acute sinusitis. Nonetheless, it is demonstrated in most studies that besides the "infernal trio" additional bacteria are present, including anaerobes and gram negative bacteria. In otitis media with effusion (OME) we find the same bacteria as in acute otitis media (AOM) and a pathologic flora in the nasopharynx seems to be important for both AOM and OME. In chronic otitis cultures are nearly always positive and reveal Pseudomonas species, Klebsiella pneumoniae, Staphylococcus aureus, Proteus species and anaerobes. PMID- 8476584 TI - Concentrations of ofloxacin in ear and nasal tissues. AB - The results of two kinetic studies examining soft tissue, cartilage and bone after uptake of oral ofloxacin [administered as 200 mg twice daily (study I/nose) or 400 mg once daily (study II/ear)] show that antibiotic concentrations lie within the therapeutic range. Findings demonstrate that 400 mg ofloxacin daily is a compliance-enhancing and effective approach to the treatment of ENT-related infections, in particular those caused by problem organisms such as Pseudomonas aeruginosa. PMID- 8476585 TI - A rapid procedure for mRNA extraction from a large number of samples. PMID- 8476586 TI - "Easypreps": fast and easy plasmid minipreparation for analysis of recombinant clones in E. coli. PMID- 8476587 TI - Multiplexed minipreps for rapid screening of large numbers of recombinant DNA clones. PMID- 8476588 TI - Optimized PEG method for rapid plasmid DNA purification: high yield from "midi prep". PMID- 8476589 TI - Simplified isolation of chromosomal and plasmid DNA from yeasts. PMID- 8476590 TI - Simplified purification of single-stranded DNA for dideoxynucleotide chain termination DNA sequencing. PMID- 8476591 TI - A simplified method of extracting DNA from gradient-purified bacteriophage lambda. PMID- 8476592 TI - Cesium chloride or column preparation? An electron microscopical view of plasmid preparations. PMID- 8476593 TI - Importance of DNA quality for transfection efficiency. PMID- 8476594 TI - Rapid shuttle plasmid preparation from yeast cells by transfer to E. coli. PMID- 8476595 TI - Improving the efficiency of mutagenesis during oligonucleotide-directed in vitro mutagenesis. PMID- 8476596 TI - An internal indicator for alkaline denaturation of double-stranded DNA in dideoxy sequencing reactions. PMID- 8476597 TI - Enhanced chemiluminescence with catalyzed reporter deposition for increasing the sensitivity of western blotting. PMID- 8476598 TI - An inexpensive approach to ultracentrifugation of small volume suspensions. PMID- 8476599 TI - Three-base pair resolution of DNA fragments on agarose: application to delta F508 analysis in cystic fibrosis. PMID- 8476600 TI - Post-hybridization recovery of membrane filter-bound DNA for enzymatic DNA amplification. AB - We describe here a simple and rapid method for enzymatic DNA amplification using DNA template recovered from membrane filters previously used in hybridization analysis. This is done by first solubilizing membrane pieces carrying DNA of interest in dimethyl sulfoxide, followed by isopropanol precipitation and polymerase chain reaction amplification. The source of membrane-bound DNA successfully tested includes plasmid and human leukocyte DNA and DNA immobilized on bacterial colony filters and plaque lifts. The sensitivity of the procedure is such that DNA recovered from 0.5 microgram of filter-bound total human DNA was enough for PCR amplification of a 0.3-kb fragment. Our protocol will be useful for recycling of scarce DNA samples for cloning and sequencing purposes. PMID- 8476601 TI - Denaturing HPLC purification of tritylated oligonucleotides using tetraethylammonium hydroxide. AB - Purification of oligonucleotides by HPLC is limited by association between failure sequences and full-length oligonucleotide. We describe a protocol for denaturing purification of 5'-dimethoxytritylated oligonucleotides that ensures that separation of tritylated and non-tritylated species will not be complicated by strand association. Fully denaturing conditions are produced by the use of tetraethylammonium hydroxide, which is a basic reagent with ion-pairing properties similar to triethylammonium acetate. The method also includes two other convenient features: a) the option of loading the crude oligonucleotide without removing concentrated ammonium hydroxide and b) detritylation on the column with separation of dimethoxytrityl alcohol. PMID- 8476602 TI - Purification of epithelial-type transforming growth factor by micro-preparative electrophoresis chromatography. AB - The purification and recovery of biologically active epithelial-type transforming growth factor (TGFe) is described. In the final phase of purification, micropreparative electrophoretic chromatography was employed using a Tris-glycine sodium dodecyl sulfate buffer system in an automated instrument. Briefly, partially purified protein preparations were separated in 2.5 x 50 mm, 10% polyacrylamide gel in electrophoresis tubes installed in the apparatus, electrophoresed under constant current of 1.5 mA for 400 min and recovered by automated fractionation and collection of the eluant from the tube gel. Aliquots of the eluted fractions were assayed in a biological system using SW-13 cell growth stimulation as an indicator of the presence of biologically active TGFe. Using the above procedure, TGFe was purified to within 95% homogeneity as assessed by silver-stained sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 8476603 TI - Syringe safety modification for neat TFA delivery. PMID- 8476604 TI - Analysis of synthetic oligodeoxyribonucleotides by capillary gel electrophoresis and anion-exchange HPLC. AB - Polyacrylamide slab gel electrophoresis has been traditionally used for the analysis of synthetic oligodeoxyribonucleotides. As the demand for oligonucleotides of high purity has increased, a need for additional high resolution analytical techniques has arisen. This report describes the principles and application of capillary gel electrophoresis and high-performance liquid chromatography for the analysis of synthetic DNA varying in base composition and length. From the results of a series of comparative experiments, the relative advantages and disadvantages of each technique are discussed. PMID- 8476605 TI - Screening for point mutations by semi-automated DNA sequencing using sequenase and magnetic beads. AB - We have established an improved method for detecting point mutations by semi automated DNA sequencing of PCR fragments generated from genomic DNA. The method employs magnetic beads to create immobilized single-stranded DNA templates, and the sequencing reaction is performed with Sequenase. This method is superior to sequencing with Taq DNA polymerase because the uniform peak height with Sequenase makes heterozygosity easily detectable as double peaks that are half the normal height. Detection of heterozygosity by this method is illustrated by sequencing a 180-bp fragment of the human apolipoprotein B gene. This fragment contains codon 3500, where a point mutation (3500CGG-->CAG) is found in subjects with the autosomal dominant disease familial defective apolipoprotein B. The nonuniform peak height with Taq DNA polymerase makes it more difficult to detect heterozygosity. This is also illustrated by sequencing a 278-bp fragment of the low-density lipoprotein receptor gene. PMID- 8476606 TI - Plasmid rescue from transgenic mouse DNA using LacI repressor protein conjugated to magnetic beads. AB - A method for the efficient rescue of lac operator containing plasmids from transgenic mouse genomic DNA is described. The method is based on the high affinity of the LacI repressor protein for the lac operator sequence. Using the LacI repressor protein conjugated to magnetic beads, more than 95% of plasmid sequences could be purified from restriction enzyme digested genomic DNA. After circularization, the plasmids were introduced into Escherichia coli by means of electroporation. Since the plasmid was cloned into a bacteriophage lambda vector, the efficiency of plasmid rescue could easily be compared with in vitro packaging. Our results indicate that plasmid rescue is about 25 times more efficient. Application of this method should be especially useful with transgenic mouse models harboring LacZ plasmid shuttle vectors for studying spontaneous or induced mutations in vivo. PMID- 8476607 TI - Matrix effects in the derivatization of amino acids with naphthalene dicarboxaldehyde, 9-fluorenylmethyl chloroformate and phenylisothiocyanate. AB - Pre-column derivatizations of amino acids often present two major challenges: 1) automation, due to the multi-step manipulations for pH control, reagent addition, mixing and extraction, and 2) effect of matrices in the sample such as salts, buffers and surfactants. Both issues have been addressed in a previous publication on derivatization methods using 9-fluorenylmethyl chloroformate (FMOC) and phenylisothiocyanate (PITC). In this paper, a third method of derivatization, which has recently been developed and published, was studied to address the same issues. The derivatization reagent, naphthalene-2,3 dicarboxaldehyde (NDA), is a modification from o-phthalaldehyde (OPA) and yields more stable derivatives with high fluorescence efficiencies. An autosampler was programmed to mix amino acid samples with cyanide and NDA reagent, allow a programmed reaction time and finally inject onto the HPLC. To study sample matrix effects, amino acid samples were spiked with various concentrations of Tris-HCl, phenol, citrate, sulfosalicylic acid, sodium chloride and sodium dodecyl sulfate. The recoveries of amino acids in varied sample matrices were compared to pure amino acid standards. The matrix effects using the NDA method were similar to those using the FMOC method. Comparisons of all three methods (NDA, FMOC and PITC) are discussed and tabulated. PMID- 8476608 TI - Sample preparation for HPLC by Centricon ultrafiltration. AB - Peptides and other bioactive materials can be purified from complex biological sources by reverse-phase high-performance liquid chromatography (RP-HPLC), provided the mixture is suitably prepared before injection onto an HPLC system. Ultrafiltration offers a convenient and rapid sample preparation technique with numerous advantages over alternative methods such as conventional gel filtration chromatography. We demonstrate the use of ultrafiltration as an HPLC sample preparation step in the purification of peptides bound to class I major histocompatibility complex (MHC-I) membrane proteins. When ultrafiltration was performed with a Centricon-10 ultrafiltration device, peptides were efficiently separated from the alpha (45 kDa) and beta 2m (12 kDa) chains of MHC-I proteins and could be subjected to HPLC without further treatment. Furthermore, even samples as crude as whole cell lysates or supernatants could be prepared for HPLC in a single ultrafiltration step, affording a remarkably straightforward route to the purification of biologically important peptides. PMID- 8476609 TI - Circadian clock functions localized in xenopus retinal photoreceptors. AB - A circadian oscillator that regulates visual function is located somewhere within the vertebrate eye. To determine whether circadian rhythmicity is generated by retinal photoreceptors, we isolated and cultured photoreceptor layers from Xenopus retina. On average, 94% of the viable cells in these preparations were rod or cone photoreceptors. Photoreceptor layers produced melatonin rhythmically, with an average period of 24.3 hr, in constant darkness. The phase of the melatonin rhythm was reset by in vitro exposure of the photoreceptor layers to cycles of either light or quinpirole, a D2 dopamine receptor agonist. These data indicate that other parts of the eye are not necessary for generation or entrainment of retinal circadian melatonin rhythms and suggest that rod and/or cone photoreceptors are circadian clock cells. PMID- 8476610 TI - Circadian regulation of iodopsin gene expression in embryonic photoreceptors in retinal cell culture. AB - A circadian clock regulates a number of diverse physiological functions in the vertebrate eye. In this study, we show that mRNA for the red-sensitive cone pigment, iodopsin, fluctuates with a circadian rhythm in chicken retina. Transcript levels increase in the late afternoon just prior to the time of cone disc shedding. Furthermore, iodopsin mRNA levels are regulated similarly by a circadian oscillator in primary cultures of dispersed embryonic chick retina. Nuclear run-on experiments show that the circadian regulation of iodopsin transcript abundance occurs at the level of gene transcription. Our results provide a demonstration of clock-regulated gene expression in a vertebrate preparation maintained in cell culture. PMID- 8476611 TI - Molecular mechanisms of pain: serotonin1A receptor agonists trigger transactivation by c-fos of the prodynorphin gene in spinal cord neurons. AB - By using spinal cord neurons cultured in chemically defined medium, a double labeling procedure, and blockage with antisense oligonucleotides, we show that induction of c-fos and the subsequent transactivation of the prodynorphin gene are coupled events, triggered by serotonin1A receptor agonists. Addition of the specific 1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) to the culture, at concentrations similar to that needed for transactivation of the prodynorphin gene, also significantly increases cAMP levels. Furthermore, in rats depleted of serotonin by intrathecal administration of 5,7-dihydroxytryptamine, the induction of prodynorphin after noxious stimulation is dramatically decreased compared with the induction in sham-operated rats. These results suggest that the expression of the prodynorphin gene in spinal cord is under the control of the raphe-spinal efferents containing serotonin. PMID- 8476612 TI - Axotomy-induced neurofilament phosphorylation is inhibited in situ by microinjection of PKA and PKC inhibitors into identified lamprey neurons. AB - Close axotomy of identified lamprey neurons induces phosphorylation of somatodendritic neurofilaments (NFs), followed by ectopic regeneration of neurofilamentous sprouts from the dendrites. We used in situ intracellular microinjection to study the mechanism of axotomy-induced NF phosphorylation. We found that inhibitors of protein kinase C (PKC) and protein kinase A (PKA) block somatodendritic NF phosphorylation for up to 15 days when injected at the time of axotomy. Injection of PKA catalytic subunit, diacylglycerol, or okadaic acid induces somatodendritic NF phosphorylation in intact neurons with the same time course as close axotomy. These results suggest that transient activation of PKC, PKA, and/or serine phosphatase inhibition by axotomy triggers persistent intracellular changes that may be related to polarity loss in these neurons. PMID- 8476613 TI - Subcellular localization of tau mRNA in differentiating neuronal cell culture: implications for neuronal polarity. AB - A primary neuronal cell culture derived from whole brains of fetal rats was used to analyze the subcellular localization of tau mRNA, employing nonisotopic detection by in situ hybridization. The culture exhibited a developmental differentiation pattern previously described for neuronal cells in vivo; i.e., a transition from immature to mature tau isoforms as well as segregation of tau into the axons. Our results demonstrate that unlike tubulin mRNA, which is confined to cell bodies, or MAP2 mRNA, which extends into dendrites, tau mRNA was observed to enter the proximal portion of the axon. This sorting of tau mRNA might explain how the tau protein could be selectively delivered to the axon and could have important implications for the development of neuronal polarity. PMID- 8476614 TI - Opioid peptide modulation of Ca(2+)-dependent K+ and voltage-activated Ca2+ currents in bovine adrenal chromaffin cells. AB - Opioid peptides are abundantly expressed in the adrenal medulla, and there is evidence that they may be released presynaptically or as medullary paracrine agents. To assess the physiological relevance of these observations, we investigated opioid effects on ionic currents from cultured bovine adrenal chromaffin cells. Under whole-cell path-clamp conditions, opioid peptides, acting via a mu-type opioid receptor, strongly potentiated the large conductance Ca(2+) dependent K+ (BK) channel current. Opioids also inhibited voltage-activated Ca2+ currents. Application of opioid peptides to the extracellular face of outside-out patches also increased opening activity of single BK channels, suggestive of tight receptor-channel coupling. This potentiating effect on BK current, combined with the inhibition of Ca2+ current, indicates that opioids may have an inhibitory influence on secretory activity of the adrenal medulla. The widespread distribution of the BK channel class suggests that the significance of its modulation by opioids could also extend beyond the adrenal gland. PMID- 8476615 TI - Effect of lumbar epidural anesthesia on ventilatory response to hypercapnia in young and elderly patients. AB - STUDY OBJECTIVE: To examine the influence of age on resting ventilation, arterial blood gas tensions, and the ventilatory response to hypercapnia in lumbar epidural anesthesia. DESIGN: Clinical study using groups of young and elderly patients. SETTING: Surgical operation center of a university hospital. PATIENTS: Seven young (average age 39 years) and seven elderly (average age, 69 years) unpremedicated patients undergoing lower abdominal surgery. INTERVENTIONS: Patients were administered lumbar epidural anesthesia with 10 ml of 2% lidocaine. MEASUREMENTS AND MAIN RESULTS: Resting ventilation, arterial blood gas tensions, and ventilatory response to hypercapnia were measured before and 20 minutes after the block. Regarding the ventilatory response to hypercapnia, the mean slope of the hypercapnic response curve [change in minute ventilation (VE) divided by change in end-tidal partial pressure of carbon dioxide (PETCO2)] increased significantly following the epidural block, by 16% in the young patients and by 23% in the elderly patients, and the mean VE at a PETCO2 of 55 mmHg (VE55) also increased significantly, by 16% in the young subjects and by 26% in the older subjects. These changes in delta VE/delta PETCO2 and VE55 were statistically equivalent between the two age-groups. CONCLUSIONS: The effects of lumbar epidural anesthesia on resting ventilation, arterial blood gas tensions, and ventilatory response to hypercapnia were not affected by age. PMID- 8476616 TI - Improved postoperative analgesia with morphine added to axillary block solution. AB - STUDY OBJECTIVE: To determine whether the addition of morphine to the axillary block local anesthetic solution provides improved or prolonged postoperative analgesia. DESIGN: Prospective, randomized, double-blind clinical trial with 24 hour follow-up. SETTING: Ambulatory unit of a large academic referral center. PATIENTS: Consecutive healthy volunteers scheduled for elective upper extremity surgery. INTERVENTIONS: Patients in the treatment group (AX) were given intravenous (IV) saline and had morphine 0.1 mg/kg added to their axillary block solution. Control subjects (CT) received morphine 0.1 mg/kg IV and had saline added to their axillary block solution. All axillary blocks were performed using 0.55 ml/kg of 1.5% lidocaine with epinephrine 1:200,000. MEASUREMENTS AND MAIN RESULTS: During the first 24 hours after surgery, visual analog scale (VAS) scores, supplementary analgesic (oxycodone 5 mg with acetaminophen 500 mg) use, and complications were recorded. Both groups had similar VAS scores throughout the study. In the 24-hour postoperative study period, AX patients required approximately half as many doses (median, 2 doses; range, 0 to 7 doses of supplemental analgesic as CT patients (median, 4 doses; range, 0 to 12 doses). There were no major complications in either group. CONCLUSIONS: The addition of morphine 0.1 mg/kg to the local anesthetic axillary block solution provided improved postoperative analgesia without an increased frequency of side effects or major complications. PMID- 8476617 TI - Interpleural analgesia with bupivacaine following thoracotomy: ineffective results of a controlled study and pharmacokinetics. AB - STUDY OBJECTIVE: To evaluate intrapleural analgesia with bupivacaine following partial pulmonary resection and to determine pharmacokinetic parameters of bupivacaine with epinephrine. DESIGN: Prospective, randomized study. SETTING: Thoracic surgical clinic of a university-affiliated general hospital. PATIENTS: Eighteen consecutive patients (13 men, 5 women) scheduled for pulmonary surgery by posterolateral thoracotomy. INTERVENTIONS: Bupivacaine was administered through an intrapleural catheter as a bolus dose of either 40 ml of 0.25% bupivacaine with epinephrine (0.5 mg per 100 ml of solution) (n = 10) or 20 ml of 0.5% bupivacaine with epinephrine (0.5 mg per 100 ml of solution) (n = 8) up to three times daily for a maximum time of 4 days. MEASUREMENTS AND MAIN RESULTS: Subjective evaluation of pain was performed using the visual analog scale (VAS) before and after each injection by response to spontaneous pain, coughing, deep breathing, and incision palpation. Maximum peak concentration (C Max) and maximum time to reach the peak concentration (T Max) were assessed after the first and last injections. Although VAS pain score decreased significantly, pain relief was not sufficient. C Max and T Max after the first and last injections were not significantly different between the two groups. In each group, C Max after the last injection was significantly higher than after the first injection. CONCLUSIONS: Intrapleural analgesia conducted with 40 ml of 0.25% bupivacaine with epinephrine or 20 ml of 0.5% bupivacaine with epinephrine was insufficient for pain, despite high plasma bupivacaine concentration. PMID- 8476618 TI - A comparison of desflurane and isoflurane in prolonged surgery. AB - STUDY OBJECTIVE: To compare desflurane with isoflurane in several anesthetic situations. DESIGN: Intubating conditions, hemodynamic response to intubation, maintenance hemodynamics, and speed of recovery from desflurane and isoflurane anesthesia were evaluated. In addition, interaction with a muscle relaxant at low and high concentrations of the anesthetics were compared. SETTING: Thomas Jefferson University Hospital. PATIENTS: Thirty-two patients who received general anesthesia for lengthy, mostly orthopedic procedures. INTERVENTIONS: Immediately after induction with thiopental sodium, desflurane or isoflurane in nitrous oxide oxygen was administered via face mask. Anesthesia was deepened until end-tidal concentration reached 1.7 minimum alveolar concentration (MAC). The trachea was intubated without the aid of a muscle relaxant. Heart rate (HR) and blood pressure (BP) were recorded before and at 1, 2, 4, 5, and 10 minutes after intubation. Noninvasive cardiac output (CO) and systemic vascular resistance (SVR) were determined while the patient was awake, immediately before intubation, and at 5 and 10 minutes after intubation. Following intubation, the concentration of desflurane or isoflurane was lowered until the end-tidal concentration reached 0.65 MAC (low-MAC group), 1.25 MAC (high-MAC group), or 0 MAC (control group). Pancuronium bromide in 0.005 mg/kg doses was administered incrementally until T1 (first twitch of train-of-four) was depressed more than 90%. ED50 and ED95 for pancuronium with balanced anesthesia and for desflurane or isoflurane in low and high MACs, as well as speed of recovery, were determined. The time to responsiveness and awakening also was determined. MEASUREMENTS AND MAIN RESULTS: There was no significant difference between desflurane and isoflurane in intubating conditions or in BP or HR response to tracheal intubation. Both anesthetics increased HR significantly during induction. BP rose with desflurane at the preintubation point; other points showed no difference. A hyperdynamic response of increased HR and BP above 20% of baseline values was seen more frequently with desflurane (n = 7) than with isoflurane (n = 1). CO was elevated at all times after induction for low and high concentrations of both drugs, while SVR decreased over the same time with no significant difference between drugs. ED50 and ED95 for pancuronium were similar under desflurane and isoflurane at both low and high MAC, but they were significantly lower than under balanced anesthesia. Awakening times were similar for desflurane and isoflurane. CONCLUSIONS: Desflurane is similar to isoflurane in providing anesthesia for intubation and maintenance. Desflurane tends to increase HR and occasionally causes a hyperdynamic response during rapid deepening of anesthesia. It is very similar to isoflurane in its interaction with pancuronium. PMID- 8476619 TI - Continuous caudal anesthesia for inguinal hernia repair in former preterm infants. AB - STUDY OBJECTIVE: To determine the feasibility of continuous caudal anesthesia with 2-chloroprocaine in conscious former preterm infants undergoing inguinal hernia repair. DESIGN: Prospective study. SETTING: University-affiliated children's hospital. PATIENTS: Ten former preterm infants, ASA physical status II and III, who were 35 to 49.5 weeks postconceptional age at the time of surgery. INTERVENTIONS: Caudal anesthesia was administered via an indwelling catheter using a loading dose of 1 ml/kg (30 mg/kg) of 3% 2-chloroprocaine, followed by incremental doses of 0.3 ml/kg (9 mg/kg) to achieve a level of T4 to T2. The block was maintained by a minimum infusion rate of 30 mg/kg/hr (1 ml/kg/hr) of the same local anesthetic solution. MEASUREMENTS AND MAIN RESULTS: The mean cumulative dose of 2-chloroprocaine was 2.8 +/- 1.0 ml/kg/hr (84 +/- 30 mg/kg/hr) infused over a mean duration of 95 +/- 35 minutes. Serum cholinesterase concentration and plasma 2-chloroprocaine concentration were measured in five infants. CONCLUSIONS: Three percent 2-chloroprocaine can be used effectively for continuous caudal anesthesia in conscious, former preterm infants for inguinal hernia and penoscrotal surgical procedures lasting 85 to 170 minutes. PMID- 8476620 TI - Hemodynamic stability and patient satisfaction after anesthetic induction with thiopental sodium, ketamine, thiopental-fentanyl, and ketamine-fentanyl. AB - STUDY OBJECTIVE: To examine three commonly used anesthetic induction regimens (thiopental sodium, ketamine, and thiopental plus fentanyl) and one newly described regimen (ketamine plus fentanyl) with respect to hemodynamic stability and patient satisfaction. DESIGN: Randomized, double-blind study. SETTING: University-affiliated Veterans Administration Hospital. PATIENTS: Forty-eight ASA physical status I and II patients (47 males, 1 female) scheduled for surgery requiring general anesthesia. INTERVENTIONS: Patients were randomized to one of four groups to receive intravenous injections of thiopental 5 mg/kg (Group 1), ketamine 1.5 mg/kg (Group 2), thiopental 3 mg/kg plus fentanyl 4 to 6 micrograms/kg (Group 3), or ketamine 0.5 mg/kg plus fentanyl 4 to 6 micrograms/kg (Group 4) for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Heart rate (HR) and mean arterial pressure (MAP) were measured during anesthetic induction. Evaluation of patient satisfaction/dissatisfaction and pleasantness/unpleasantness by the Anesthesia Experience Rating (AER) was carried out the day following surgery. Groups 3 and 4 showed the least increase from their baseline values in both HR and MAP after tracheal intubation, but only Group 4 exhibited no statistically significant change in hemodynamic parameters after induction but before intubation (p < 0.05). AER showed a higher level of pleasantness in Group 3 as compared with Group 2 (p < 0.03) and higher levels of satisfaction in Groups 3 (p < 0.03) and 4 (p < 0.02) as compared with Group 2. CONCLUSION: The combination of ketamine plus fentanyl provides superior hemodynamic stability with excellent patient satisfaction. PMID- 8476621 TI - Ectasis and pallor of peripheral airways during mechanical ventilation. AB - STUDY OBJECTIVE: To evaluate morphologic changes in peripheral airways associated with positive-pressure ventilation (PPV). DESIGN: Single-blind study. SETTING: Intensive care unit of a university hospital. PATIENTS: Ten patients who required mechanical ventilation due to acute respiratory failure but had no history of prior pulmonary disease. INTERVENTIONS: Seventeen fiberoptic bronchoscopy procedures were performed using a fine fiberoptic bronchoscope of 1.8 mm outside diameter. MEASUREMENTS AND MAIN RESULTS: The main morphologic findings were pallor and ectasis. Increased secretions, pigmentation, and stenosis or collapse in peripheral airways also were observed. Patients with ectasis were more likely to have had prolonged mechanical ventilation (17 +/- 9 days) as compared with those patients without ectasis (9 +/- 5 days). CONCLUSION: The structural alterations in peripheral airways noted in patients on prolonged PPV suggest that barotrauma may be more widespread than previously recognized. PMID- 8476622 TI - Adult epiglottitis and postobstructive pulmonary edema in a patient with severe coronary artery disease. AB - Epiglottitis is a rare cause of upper airway obstruction that may lead to death in the adult. We report the case of a patient with severe coronary artery disease with adult epiglottitis who required emergency endotracheal intubation. Relief of the airway obstruction was followed by the development of postobstructive pulmonary edema. The literature is reviewed and the following recommendations are made: Patients with adult epiglottitis should be intubated in the presence of any respiratory signs or symptoms. All others should be observed in an intensive care unit with a skilled anesthesiologist available to carry out emergency endotracheal intubation. Inhalation induction with halothane in oxygen should be considered initially; failing that, rigid bronchoscopy, tracheostomy, or transtracheal ventilation should be available. Postobstructive pulmonary edema should be anticipated after relief of airway obstruction has occurred; it can be treated with fluid restriction, diuretics, and continuous positive airway pressure. PMID- 8476623 TI - Crawford W. Long: pioneer physician in anesthesia. AB - Crawford W. Long first used ether as an anesthetic on March 30, 1842. This article examines factors in his education and practice that prompted his discovery. Included in the discussion are some of the circumstances that caused Long to delay publication of his experience with ether, as well as the impact of the "ether controversy" on his life. PMID- 8476624 TI - High-cost, high-tech medicine: are we getting our money's worth? AB - Increasingly stringent fiscal restraints on the spending for health care, driven by the scarcity of health resources, has introduced a need to apply cost containment measures to nearly all aspects of medical care. Intelligent cost containment measures must include application of disciplined logic to the decision making process of when to use high-tech, high-cost interventions. Such decision making depends upon knowledge of the basic concepts of economic and cost benefit analyses, outcome (benefit) studies, and some principles of decision threshold analysis. These basic principles are reviewed, and the potential impact of application of strategies for cost containment in the operating room and the intensive care unit is discussed. PMID- 8476625 TI - Moving toward value-based anesthesia care. PMID- 8476626 TI - Coagulation studies in the preeclamptic parturient: a survey. AB - STUDY OBJECTIVE: To delineate current practice with regard to how coagulation status is evaluated before induction of regional anesthesia in the preeclamptic parturient, with the goal of defining appropriate testing. DESIGN: A confidential survey was mailed to the chairmen of all 113 anesthesiology residency training programs in the United States listed in the American Medical Association's American Medical Graduation Education guide, to be passed on to the director of obstetric anesthesia. SETTING: Academic institutions providing obstetric anesthesia services in the United States. INTERVENTIONS: Following the original study, there was no additional follow-up or intervention. MEASUREMENTS AND MAIN RESULTS: The 21-question survey explored institutional characteristics such as the number of deliveries, the use of regional anesthesia, and the laboratory tests required prior to placement of a regional anesthetic in the mildly or severely preeclamptic parturient under two degrees of operative urgency. In the 74 programs entered into the analysis, we found that regional anesthesia was used in the majority of cesarean sections and more than half of the vaginal deliveries. In an urgent situation, most of the programs required no test of coagulation status in the mild preeclamptic parturient and only a platelet count in the severe preeclamptic parturient. CONCLUSIONS: In the majority of academic programs in the United States, we found that the evaluation of coagulation status in the preeclamptic parturient was based primarily on a platelet count. A review of the literature supports this pattern of testing. PMID- 8476627 TI - Mechanisms of eosinophil recruitment. AB - As with other types of leukocytes, mechanisms that function to enable the recruitment of eosinophils into specific sites of immune reactions involve a complex and cumulative interplay of many molecules and pathways. No single chemoattractant is specific for eosinophils, but rather various chemoattractants active on eosinophils can also elicit migration of other specific cell types. Humoral mediators causing eosinophil migration include C5a and platelet activating factor, whereas cytokines active as eosinophil chemoattractants include interleukin (IL)-2, IL-3, IL-5, granulocyte/macrophage colony-stimulating factor, lymphocyte chemoattractant factor, and RANTES. Eosinophils utilize several pathways to adhere to vascular endothelial cells, including binding to intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). The lack of binding of neutrophils to VCAM-1 and the enhanced expression of VCAM-1 elicited by IL-4 contribute to preferential eosinophil accumulation. Eosinophil recruitment is dependent not only on ligands expressed on eosinophils and molecules inducible on endothelial cells but also on processes active during transendothelial migration and extravascular migration in the extracellular spaces. PMID- 8476628 TI - Pathogenesis of Pneumocystis carinii pneumonia. PMID- 8476629 TI - Enhanced secretion of immune-modulating cytokines by human lung fibroblasts during in vitro infection with Mycoplasma fermentans. AB - Fibroblasts may play an important role in the modulation of immune and inflammatory responses through elaboration of cytokines. To test this hypothesis, human lung fibroblasts were isolated from transbronchial biopsy specimens and assayed for production of interleukin-6 (IL-6) and granulocyte/macrophage colony stimulating factor (GM-CSF). The sources of fibroblasts included lung allografts, recipient lungs obtained at time of transplant, and normal lung tissue removed during tumor resection. During the course of these studies, several early-passage fibroblasts from transplant recipients were observed to contain mycoplasma (MP) like organisms as detected by extranuclear fluorescent staining with Hoechst 33258. Positive staining cultures were associated with isolation of Mycoplasma fermentans. IL-6 and GM-GSF as measured by ELISA were found to be elevated over 50-fold in conditioned medium from MP-infected fibroblasts as compared with noninfected lines. Treatment of cells with mycoplasma removal agent (MRA) eliminated extranuclear Hoechst fluorescence and significantly reduced the production of these cytokines. Tumor necrosis factor-beta (TNF-beta) induction of IL-6 and GM-CSF was amplified synergistically in infected cultures. No additional production of IL-6 or GM-CSF was observed in infected cultures treated with interferon-gamma (IFN-gamma) despite the ability of IFN-gamma to modestly induce IL-6 in uninfected cultures. Thus, in vitro infection of lung fibroblasts with MP represents a potent stimulus for the production of inflammatory cytokines and, therefore, necessitates rigorous control for these organisms in cell culture studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476630 TI - Cytokines contribute to airway dysfunction in antigen-challenged guinea pigs: inhibition of airway hyperreactivity, pulmonary eosinophil accumulation, and tumor necrosis factor generation by pretreatment with an interleukin-1 receptor antagonist. AB - The role of pro-inflammatory cytokines in an animal model of allergic lung disease was examined by use of an interleukin-1 receptor antagonist (IL-1ra) and a specific bioassay for tumor necrosis factor (TNF). Ovalbumin-sensitized guinea pigs exhibit a marked bronchial hyperreactivity (assessed by airway responsiveness to intravenous histamine) and pulmonary eosinophil accumulation (assessed by bronchoalveolar lavage) 24 h after challenge with aerosolized antigen. Exposure of animals to an aerosol of IL-1ra (50 micrograms over 30 min) immediately before antigen challenge resulted in a marked protection against bronchial hyperreactivity and pulmonary eosinophil accumulation compared with IL 1ra vehicle-pretreated animals. Additionally, we report for the first time generation of TNF bioactivity in the bronchoalveolar lavage of antigen-challenged animals, which was significantly reduced in animals exposed to aerosolized IL-1ra before challenge. These studies point to a key role for the cytokines IL-1 and possibly TNF in the pulmonary changes observed during allergic airway disease. PMID- 8476631 TI - Alveolar macrophage release of tumor necrosis factor during murine Pneumocystis carinii pneumonia. AB - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine produced principally by mononuclear cells, is released in response to a variety of pulmonary pathogens. We hypothesized that release of TNF in the lung is a normal part of the host response to intratracheal challenge with Pneumocystis carinii. To test this hypothesis, we measured TNF in bronchoalveolar lavage fluid (BALF) in normal and CD4-depleted mice at various intervals in acute and chronically infected animals. To assess the cell of origin and the control of TNF release in the lung, we measured mRNA for TNF by a competitive polymerase chain reaction and assessed the capacity of adherence-enriched cells to produce TNF in vitro in response to lipopolysaccharide. Our data demonstrate that TNF peaks at 3 h in both control and CD4-depleted mice after acute challenge with P. carinii and this increase in TNF precedes the influx of inflammatory cells into the lung. TNF levels in BALF return to undetectable levels by day 3. In chronically infected animals, there is a 5-fold increase in mRNA for TNF in adherent cells which is associated with an increased capacity to release TNF in vitro. These data suggest that TNF is a normal host response to P. carinii infection; however, there is no difference in acute TNF release between control animals that clear their infection and CD4-depleted animals that develop chronic infection. TNF is upregulated in chronically infected animals, but CD4 depletion results in the loss of additional host factors essential for resolution of this infection. PMID- 8476632 TI - Isolation and partial characterization of subpopulations of alveolar macrophages, granulocytes, and highly enriched interstitial macrophages from rat lung. AB - The contribution of interstitial macrophages (IM) to lung defense, homeostasis, and pathophysiology is for the most part unknown. Studies on this cell type are difficult because they are not readily accessible in large numbers or in high purity. In the present work, various nonenzymatic and enzymatic methods were compared with the aim of isolating and characterizing pure populations of lung IM. The results of our studies demonstrate that most procedures currently used to isolate IM yield subpopulations of alveolar macrophages (AM) or IM highly contaminated by AM and granulocytes. We found that lavage of the lung yielded only one half of the total AM present in the tissue. The remainder of the AM could only be obtained by extensive washing of cut and disaggregated lung tissue, which is considered by some investigators to be an effective procedure for IM isolation. According to our results, cells recovered by lavage and washing of cut and disaggregated lung tissue were morphologically and histochemically identical, were strongly positive for nonspecific esterase, highly phagocytic, and appeared to represent subpopulations of AM with apparently varying degrees of adherence to the alveolar walls. We also found that IM could be obtained in high purity by sequential digestion of the remaining lung tissue with 60 and 175 IU/ml of collagenase followed by selective adherence. Digestion of the tissue with 60 IU/ml of collagenase resulted in a highly enriched population of granulocytes and also reduced their contamination in the IM population. The resulting IM were distinct from AM by morphology and histochemistry. Like AM, these cells displayed Fc receptor-mediated phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476633 TI - Endothelin in human nasal mucosa. AB - Endothelin (ET), a potent vasoconstrictor and bronchoconstrictor peptide synthesized by endothelial and epithelial cells, was examined for its potential functions in human inferior turbinate nasal mucosal tissue by four techniques: (1) immunoreactive ET was localized in the mucosa by immunohistochemistry; (2) receptors for ET were identified by autoradiography employing [125I]ET; (3) ET-1 mRNA was localized by in situ hybridization; and (4) the secretory functions of ET were examined by the release of mucous and serous cell products after the addition of ET to human nasal turbinates in short-term cultures. Specific ET-1 immunoreactive material was found most extensively in small muscular arteries and in serous cells in submucosal glands. ET-1 was also found to a lower extent in the walls of venous sinusoids. [125I]ET-1 binding sites were localized by autoradiography to submucosal glands and to venous sinusoids and small muscular arterioles. mRNA for ET-1 was found most extensively in the venous sinusoids and to a lesser extent in small muscular arteries. In mucosal explant cultures, ET-1 and ET-2 stimulated lactoferrin and mucous glycoprotein release from serous and mucous cells, but ET-3 was inactive. The observations indicate that in the human nasal mucosa, ET is present in the vascular endothelium and the serous cells in submucosal glands and acts on glandular ET receptors to induce both serous and mucous cell secretion. It is also likely that ET plays a role in the regulation of vasomotor tone. PMID- 8476634 TI - Retinoic acid and calcium regulation of p53, transforming growth factor-beta 1, and transforming growth factor-alpha gene expression and growth in adenovirus 12 SV40-transformed human tracheal gland epithelial cells. AB - Vitamin A and calcium are important regulators of growth and differentiation of epithelial cells and are intimately involved in preneoplastic and neoplastic transformation. It has been proposed that their effects are mediated by autocrine/paracrine positive and negative regulators of growth. The objectives of this investigation were to examine the effects of all-trans retinoic acid (RA) and Ca2+ on cell proliferation, anchorage-independent growth (AIG), and on the expression of transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1 (TGF-beta 1), and p53 tumor suppressor genes in human tracheal gland epithelial (HTGE) cells immortalized by adenovirus 12-simian virus 40 (Ad12 SV40) hybrid. Cells exhibiting the transformed phenotype, AIG, were maintained in serum-free culture conditions. Calcium effects were examined at 0.15, 0.50, 1.0, and 2.0 mM concentrations. The effects of RA were determined with 10(-9), 10(-7), and 10(-6) M concentrations. Gene expression was examined by Northern and Western analyses. Ca2+ had no significant effect on cell proliferation, but it enhanced the expression of TGF-beta 1 gene and slightly inhibited p53 expression. Ca2+ had no effect on TGF-alpha. RA inhibited both cell proliferation and AIG growth, which was accompanied by enhanced expression of p53. RA had no significant effect on the expression of TGF-alpha and TGF-beta 1 genes. These results demonstrate that RA regulates growth of HTGE cells mainly by upregulating the p53 gene; Ca2+, which enhances TGF-beta 1 expression, had no effect on growth. PMID- 8476635 TI - Auto-induction of transforming growth factor-beta in human lung fibroblasts. AB - The type beta transforming growth factors (TGF-beta s) are a family of potent cytokines with diverse effects on proliferation, differentiation, turnover of extracellular matrix components, oncogene expression, and other aspects of cellular phenotype. Unlike lung fibroblasts of certain species, unstimulated human lung fibroblast lines produce little or no TGF-beta in culture. However, TGF-beta has been reported to autoregulate its own production in certain human tumor cells and in rodent cell lines. To test whether this phenomenon is operative in fibroblasts from normal human lung tissue, confluent cultures of IMR90 normal fetal lung fibroblasts were exposed to TGF-beta. Cultures were exposed briefly to purified TGF-beta 1 under serum-free conditions and secretion of newly synthesized TGF-beta over the ensuing 72 h was determined by immunoblotting and bioassays made specific with the use of neutralizing antibodies. Steady-state levels of mRNA for TGF-beta 1 were detected by Northern and slot blot hybridization analysis of total cellular RNA. The 2.5 kb TGF-beta 1 mRNA species rose within 1.5 h of exposure of IMR90 cells to TGF-beta 1 and reached maximal levels after 16 h. Increased levels of TGF-beta were detected in conditioned medium 9 h after the start of the exposure. Thereafter, TGF-beta continued to accumulate at an elevated rate (90 +/- 7 versus < or = 15 pg/10(6) cells/h in uninduced cells) for up to 72 h. As little as 1 ng/ml TGF-beta 1 auto induced TGF-beta secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476636 TI - Submucosal tissues modulate the bioelectric properties of airway epithelium. AB - Exposure of isolated canine tracheal epithelium to acetylcholine (Ach) increased transepithelial conductance (GT) and short-circuit current (ISC). Qualitatively different responses were obtained when the epithelium was studied as a part of an intact posterior tracheal membrane that contained smooth muscle. Ach decreased GT, did not affect ISC, and induced a 2-fold increase in measured tension. In these tissues, baseline GT was enhanced compared with that of isolated epithelium. Indomethacin inhibited the Ach-induced responses of isolated epithelium but did not alter the responses of intact airway tissue. The epithelial origin of these electrophysiologic responses was confirmed in experiments that showed that denudation of intact tracheal tissue greatly increased base-line GT, eliminated ISC, abolished the electrophysiologic response to Ach, and enhanced Ach-induced smooth muscle constriction. The qualitatively different responses to Ach of intact tracheal membrane and epithelium alone suggest that the behavior of airway epithelia in the whole animal may be significantly different from that observed in conventional in vitro studies of isolated epithelia. PMID- 8476638 TI - Display and perception of ultrasound images. PMID- 8476637 TI - Characterization and gene sequence of the precursor of elafin, an elastase specific inhibitor in bronchial secretions. AB - Human bronchial mucous secretions have been shown to contain inhibitors of serine proteinases secreted by neutrophils. The role of these inhibitors is probably to control the enzymes secreted in the airways and in the lung interstitium. Three of these inhibitors have been identified and characterized: alpha 1-proteinase inhibitor, mucus proteinase inhibitor, and elafin. The elafin molecule, a 6.0 kD inhibitor of serine proteinases shows homology with mucus proteinase inhibitor. We recently isolated both molecules in bronchial secretions. In this report, we present evidence for the existence of a precursor of the elafin molecule. We have cloned and sequenced the gene for this precursor and show that it is composed of three exons. The coding information for a 117 amino acid precursor protein of elafin (inclusive of the signal peptide) is contained in the first two exons. This was confirmed at the mRNA and protein levels. By Northern Blot analysis we detected a 800 bp long product, and by immunoaffinity we detected in sputum and in cultured epithelial cell supernatant (NCI-H322 cell line) a 12 kD protein species cross-reacting with anti-elafin IgG. The finding of possible cross linking function for the precursor in addition to its antiproteinase activity indicates a possible role for this molecule as a cross-linker agent in the extracellular matrix. PMID- 8476639 TI - Ultimate limits in ultrasound image resolution. PMID- 8476640 TI - Blood flow quantitation: waveform analysis, volume measurement, tumor flow, and the role of color imaging. PMID- 8476641 TI - Ultrasound picture archiving and communication systems. AB - In this chapter, we discussed the concept of PACS infrastructure and the methods of implementing an ultrasound PACS. An ultrasound PACS differs from other radiologic PACS modules in several aspects. First, ultrasound image acquisition requires the interaction from the operator to initiate the image capture process. Second, ultrasound display requires pseudocolor to show flow images. Third, ultrasound examinations include dynamic studies that generate many images in real time. The last feature is difficult to achieve even with current technology. One method is to explore video transmission, storage, and display technology. We have researched and implemented a fiber optic broadband video system for transmitting, archiving, and displaying CT and MR images in real-time. This system connects three CT and three MR scanners in three buildings including the CHS and the MP over a distance of about 2.5 km. We believe this technology can be extended for real-time video ultrasound image transmission, archiving, and display. PMID- 8476642 TI - Impact of safety considerations on ultrasound equipment design and use. PMID- 8476643 TI - Quality management of ultrasound diagnosis. PMID- 8476644 TI - Probes as used in cardiology with emphasis on transesophageal and intravascular applications. PMID- 8476645 TI - Ultrasound contrast agents. PMID- 8476646 TI - Advances in imaging techniques. PMID- 8476647 TI - Speckle reduction. PMID- 8476648 TI - Three-dimensional imaging. PMID- 8476649 TI - Needle guidance techniques. PMID- 8476650 TI - Techniques for color-flow imaging. PMID- 8476651 TI - [The pyramidal tract in man]. PMID- 8476652 TI - [SPECT (single photon emission computed tomography) findings in 4 cases of neuronal migration disorders]. AB - We report SPECT findings in four children with various types of neuronal migration disorders. SPECT of a patient with heterotopia showed a protrudent abnormal shadow into the centrum semiovale, the density of which was same as that of normal gray matter. The function and the metabolism of heterotopia appear same as those of the normal gray matter. SPECT of a patient with pachygyria showed decreased blood flow in the areas of thickened cortex. This finding seems to indicate hypofunction of those lesions. SPECT of a patient with hemimegalencephaly showed an increased blood flow in the ipsilateral hemisphere and decreased blood flow in the contra-lateral hemisphere. In the literature, increased contents of neuronal elements in the affected site and arterio-venous shunt with cardiac failure have been reported in hemimegalencephaly. These pathologies may be related to our SPECT findings. SPECT of a patient with cortical dysplasia showed extensive lesions of decreased blood flow which was more wide spread than abnormal lesions detected by MRI. SPECT may be more sensitive than MRI to detect cortical dysplasias. PMID- 8476653 TI - [Detection of codon 72 polymorphism of p53 gene from blood and loss of heterozygosity in brain tumors using polymerase chain reaction]. AB - p53 gene which is known as a tumor suppressor gene locates in chromosome 17p and has a polymorphism at codon 72 (Arginine CGC-->Proline CCC). In this study, we examined the frequency of polymorphism and of heterozygosity in Japanese, and the loss of p53 gene in brain tumor tissues of the patients with heterozygosity using a novel method. The frequencies of heterozygosity, arginine type, proline type were 43%, 42% and 15%, respectively. Heterozygosity was observed in 15 out of 32 patients with brain tumors and loss of heterozygosity (LOH) in these 15 cases was demonstrated in 40%. Although we are not certain whether LOH of p53 region is inevitable process of oncogenesis of some brain tumors, some false negative results may occur. This quick technique requires small amount of samples and no radioactive isotope, therefore, can be applied to detect mutation and LOH occurred in p53 region in terms of the genesis and progression of human neoplasms. PMID- 8476654 TI - [Brain injury induced by continuous infusion of endotoxin in rats--protective effects of methylprednisolone on intracerebral blood vessels]. AB - Hemorrhagic intracerebral lesions, analogous to multiple punctate hemorrhagic necrosis seen in the brain of human disseminated intravascular coagulation (DIC), can be induced in rats by continuous intravenous infusion of E. coli endotoxin lipopolysaccharide (ET) at 88.5 micrograms/hour. The occurrence of cerebral lesions increases with time of ET infusion initially, but levels off after 120 hours of the continuous administration. To investigate protective effects of methylprednisolone (MP) against intracerebral vascular injury, 122 male rats were divided into the basic endotoxemic rats without MP medication (Group 1), and MP medication of 0.2mg/kg body weight, 1.0mg/kg, 2.0mg/kg and 20.0mg/kg immediately before induction of endotoxemia (Groups 2-5), one dose of 20.0mg/kg MP at 48 hours and 2 doses at 48 and 72 hours after induction of endotoxemia (Groups 6-7), and 3 doses each of 2.0mg/kg, 20.0mg/kg and 100.0mg/kg MP for 3 days immediately before and at 24 and 48 hours after induction of endotoxemia (Groups 8-10). All surviving rats were autopsied after 120 hours of ET infusion and histologic sections were made. Multiple hemorrhagic intracerebral lesions developed in 83% (10/12) of Group 1 rats, whereas the frequency of brain lesions in Groups 4, 5, 8, 9 and 10 was significantly lower than that in Group 1 (p < 0.05). Electron microscopically, the frontal lobe cortex of Group 1 after 120 hours of ET infusion showed subendothelial dilatation containing macrophages, and perivascular accumulation of erythrocytes (diapedesis). In contrast, the frontal lobe cortex of Group 5 revealed no appreciable electron microscopic changes of intracerebral blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476655 TI - [Diagnosis of intracranial occlusive vascular disease and evaluation of extracranial-intracranial (EC/IC) arterial bypass using three-dimensional magnetic resonance angiography]. AB - The three-dimensional time-of-flight (TOF) magnetic resonance angiograms (MRA) were studied to evaluate its accuracy in the assessment of the intracranial carotid occlusive lesions, collateral circulation and also the patency of extracranial-intracranial (EC/IC) arterial bypass surgery. All occlusive lesions of the intracranial major arteries seen in conventional angiograms were revealed clearly with MRA. However MRA had its practical limitation in the evaluation of the leptomeningeal anastomosis (collateral circulation) probably due to the deterioration of contrast in its slow flow and saturation effect of the magnetization. In addition to that, MRA often exaggerated the severity of the stenotic lesions, mostly in severe cases. The post-operative state of collateral flow and the patency of EC/IC bypass could be evaluated as properly with MRA as with conventional angiography, although MRA was limited in spatial resolution and evaluation of flow direction. In conclusion, MRA was considered t be a reliable non-invasive modality as a screening examination for the evaluation of the carotid occlusive disease and as the follow-up study of the post-operative patients with EC/IC bypass surgery. PMID- 8476656 TI - [Experimental study on immunotherapy of meningeal gliomatosis with monoclonal antibody]. AB - Recently extension of malignant glioma to the spinal cord (meningeal gliomatosis: MG) has been described with increasing frequency as the advancement of the therapy for brain tumor. However, the study for clinicopathological features of MG has not been established and its therapy has still been difficult. We tried to produce experimental models of MG using nude mice and study experimental immunotherapy with human monoclonal antibody (CLN-IgG MoAb). U87-SC1 human glioma cells (5 x 10(5) in 20 microliters) were inoculated transcutaneously into the cisterna magna of BALB/c nu/nu mice using a 27-gage needle. Daily weights, neurological findings and survival time were examined. MRI scan was performed after neurological deterioration and histological examination was also performed after death. CLN-IgG MoAb was used for treatment and 15 nude mice which were inoculated with tumor cells into the cisterna magna (Day 0) were divided into three groups of 5 mice each. Group A was control group which received saline into the cisterna magna, Group B and C received 50 micrograms of CLN-IgG into the cisterna magna on Day 2 or Day 7 following inoculation of tumor cells. Efficacy of experimental immunotherapy was statistically evaluated by the difference of median survival time (MST) among three groups. All of the nude mice lost weight within 4 or 5 days after inoculation of tumor cells and developed paraplegia or tetraplegia with incontinence and died. MRI of the nude mice which showed neurological deteriorations revealed ventricular dilatation, infiltration of tumor cells to the spinal cord and spread of tumor cells into the subarachnoid space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476657 TI - [Central neurocytoma--report of a case]. AB - The authors present a case of central neurocytoma in a 23-year-old male with increased intracranial pressure syndrome. Computed tomographic (CT) scans and magnetic resonance images showed a large tumor mass with no evidence of calcification in the right lateral ventricle extending towards the third ventricle. A right transcortical-transventricular approach was performed and the tumor was totally removed. The postoperative course was uneventful and no further treatment was administered. CT shows no evidence of tumor recurrence after the six months from his surgery. Light microscopic findings suggested a diagnosis of oligodendroglioma. However, ultrastructural examinations demonstrated many dense core or clear vesicles, microtubules and synaptic like structures within the abundant cytoplasmic processes of the tumor cells which suggested neuronal differentiation. Immunohistochemical examinations showed the tumor cells to be positive for neuron-specific enolase, sporadically positive for synaptophysin, and negative for glial fibrillary acidic protein. The final histological diagnosis was central neurocytoma. Central neurocytoma was first described by Hassoun et al, in 1982. Since then, 96 cases have been reported in the literatures. Their clinicopathological features, neuroradiological findings and prognosis are discussed. PMID- 8476658 TI - [Forty-six-year-old woman with progressive external ophthalmoplegia and limb weakness]. AB - We report a 46-year-old female who presented progressive ophthalmoplegia and limb weakness. She was well until the age of 15 years when there was an onset of bilateral deafness. She became completely deaf by 20 years of age. She noted an onset of weakness in her legs when she was 27-years-old and of ptosis at 34 years of age. She was admitted to our hospital when she was 41-years-old. Neurological examination revealed near total ophthalmoplegia, bilateral ptosis, dysphagia, generalized muscle atrophy and weakness of approximately 4/5 degree, facial grimacing, athetotic movements in four limbs. Laboratory examinations revealed increase in blood lactate and pyruvate levels and diffuse low density change in the cerebral white matter in CT scans. She was thought to have a mitochondrial encephalomyopathy. She was discharged for follow-up, but her clinical course was that of a relentless deterioration. She was readmitted to our service in December 1989. She showed further progress in her weakness and muscle atrophy. Otherwise neurological examination was essentially similar to the previous one. Her cranial CT scans showed low density changes in striatum, thalamus and midbrain in addition to the white matter. Enzyme activities of the electron transport complexes revealed a moderate decrease in the succinatecytochrome c reductase activity, and the Southern blot analysis of mtDNA revealed multiple deletions in mitochondrial genomes. Two months after her admission, she developed bronchopneumonia, and expired on March 13th, 1990. Post-mortem examination revealed diffuse pallor of myeline in the cerebral white matter in K-B staining. A marked neuronal loss and gliosis were observed in putamen bilaterally. Skeletal muscles showed typical changes of mitochondrial myopathies with ragged-red fibers in Gomori-Trichrome staining, and crystalline inclusion bodies by electron microscopic observations. Some neurogenic atrophies were also seen. Oculomotor nuclei appeared intact. It was thought that she had an incomplete form of Kearns Sayre syndrome. The patient was discussed in a neurological CPC of the departments of Neurology and Pathology of Juntendo University School of Medicine. PMID- 8476659 TI - [Clinical subtypes of Parkinson's disease]. PMID- 8476660 TI - ["Pure akinesia" and progressive supranuclear palsy]. PMID- 8476661 TI - [Involuntary movement due to vascular lesion in the basal ganglia]. PMID- 8476662 TI - [Molecular genetic aspects of basal ganglia diseases]. PMID- 8476663 TI - [Neuropsychological investigation in multiple sclerosis]. AB - We studied neuropsychological performance in 10 patients with multiple sclerosis (MS). Neuropsychological test batteries consisted of Mini-Mental State Examination, Digist Span, Paired Associate Learning Test (PAL), Benton Visual Retention Test, Kohs Block-Design Test, Digit Symbol Subtest in WAIS, 'Kanahiroi" Test, Verbal Fluency and Wisconsin Card Sorting Test. In accordance with cerebral lesions on MRI, patients were divided into three groups. A: Multiple-confluent lesions, B: Discrete lesions, C: No lesion. In MS patients as a whole, performance of PAL, "Kanahiroi" Test and Verbal Fluency were significantly impaired compared with 10 age and education matched normal controls (p < 0.05), while other tests were not. In four out of five patients of A group, more than four neuropsychological tests showed below mean -2SD score of normal controls, whereas in patients of B and C group, less than three neuropsychological tests showed below -2SD score of normal controls. In conclusion, severity of cognitive impairment in patients with MS correlated with lesion extent on MRI. Patients with MS exhibited significant cognitive impairment on tasks of recent memory and mental processing speed. It is suggested that MS patients show the features of subcortical dementia. PMID- 8476664 TI - [SPECT evaluation of effect of cerebral vasodilator by the subtraction method using Tc-99m HMPAO]. AB - The effects of cerebral vasodilator are generally evaluated by observing whether the clinical improvement is applicable after the period of the drug administration. This report describes a novel approach to the evaluation for the effect of the drug using Tc-99m HMPAO. Consecutive brain Tc-99m HMPAO studies before and after a cerebral vasodilator, Ibudilast, administration were performed within 5 hours on 10 patients with cerebral infarction at chronic state. Five patients showed increased perfusion nearby the affected vascular territories after the po administration of Ibudilast. Significant changes in the brain perfusion pattern were determined using an image subtraction technique. This consecutive Tc-99m HMPAO subtraction SPECT technique seems to be useful for evaluating the therapeutic effect of cerebral vasodilator. This method can be performed within a short period of time, safely and sensibly. PMID- 8476665 TI - [A new operational method of functional neurosurgery combining micro-recording and MRI stereotaxy for the treatment of Parkinson's disease]. AB - We have developed a new operational method for stereotactic functional neurosurgery using MRI stereotaxy combined with microelectrode recording. MRI stereotaxy shows us the individual variations of thalamic configurations. The tentative target points were determined using the MRI stereotaxy assisted software system which revised the distortion of MRI images. Consequently, the accuracy and safety of the microelectrode recording were increased. This, in turn, increased the accuracy of stereotactic thalamotomy while producing encouraging operational outcomes. The effectiveness of stereotactic thalamotomy for Parkinson's disease was confirmed by these excellent operative results. The symptoms improved and the dosage of medications, including L-DOPA, decreased. Furthermore, our results indicate that the distributing area of deep sensory neurons in the thalamus extended more posteriorly and upward than previously expected. Therefore, the functional and anatomical similarity between the human and monkey thalamus was reaffirmed. In this report, based on the above data, we reevaluated the neural mechanism of tremor and the role of stereotactic functional neurosurgery for Parkinson's disease. PMID- 8476666 TI - [Correlation between induction of ischemic tolerance and expression of heat shock protein-70 in the rat hippocampus]. AB - We investigated the correlation between protection against ischemic neuronal damage by preconditioning with sublethal ischemia and the expression of heat shock protein-70 (HSP70). Three minutes of forebrain ischemia in the rat induced by four-vessel occlusion and 3 days of reperfusion was followed by 6, 8, and 10 minutes of ischemia. Seven days after the second ischemia, the brains were used for histology. Two hours, 1, 3, and 7 days after 3 or 6 minutes of ischemia, the brains were used for immunohistochemistry with an antibody raised against HSP70. Three minutes of ischemia produced no neuronal damage in the hippocampus. Six, 8, and 10 minutes of ischemia produced severe neuronal damage to CA1. However, CA1 neurons were preserved in animals subjected to 6 and 8 minutes of ischemia following preconditioning with 3 minutes of ischemia. Immunostaining showed that HSP70 was induced in the CA1 subfield 3 days after 3 minutes of ischemia. HSP70 was stained in the CA1, CA3, and CA4 subfields 1 and 3 days after 6 minutes of ischemia with or without preconditioning. However, HSP70 was also stained in CA1 2 hours and 7 days after 6 minutes of ischemia following preconditioning. These results strongly suggest that stress response induced by sublethal ischemia protects against ischemic neuronal damage. However, the protection was not seen when HSP70 synthesis was delayed. Presence of HSP70 during and immediately after ischemia may be critical for the protection against ischemic neuronal damage following preconditioning. PMID- 8476667 TI - [Two cases of well-known syndrome due to midbrain-brain stem hemorrhage--Weber's syndrome and one and a half syndrome]. AB - Two cases of well-known syndrome due to midbrain-brain stem hemorrhage without having a history of hypertension were reported. Case 1 is a 62-year-old female, presenting Weber's syndrome due to midbrain hemorrhage and diagnosed as Moyamoya disease angiographically. Case 2 is a 24-year-old-male, presenting One and a half syndrome due to brain stem hemorrhage from a brain stem cavernous angioma, which was diagnosed angiographically and by magnetic resonance imaging (MRI). Left hemiparesis seen in case 1 had improved by conservative therapy but no improvement could be obtained in the oculomotor nerve palsy. In case 2, hematoma was aspirated surgically for the purpose of decompression and his neurological symptoms improved markedly. Their pathogenesis and pathophysiology were also discussed. PMID- 8476668 TI - [Alcoholic cerebellar degeneration with pyramidal sign--in relation to alcoholic myelopathy]. AB - Two cases of alcoholic cerebellar degeneration with pyramidal sign were reported. Patient 1 with alcohol dependence syndrome was a 46-year-old woman. After the alcohol abuse of about eight years, she complained of gait disturbance. The gait disturbance progressively worsened in about two months and she could not ambulate freely by herself. Neurological examination revealed nystagmus, ataxic and spastic gait, slight weakness and spasticity of the lower extremities, hyperreflexia of the extremities, bilateral Babinski's signs, and incoordination of the lower extremities. Examination of liver function and serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis and dorsal part of the cerebellum. Though neurological signs slightly improved after the admission to our hospital and the abstinence from alcohol abuse, ataxic gait and hyperreflexia of the extremities have continued. Patient 2 was a 58-year-old man. He was a heavy drinker, but was not a patient with alcohol dependence syndrome. After the heavy drinking of about 40 years, he complained of gait disturbance. The gait disturbance had progressively worsened in about four months. Neurological examination revealed ataxic gait, hyperreflexia of the lower extremities, and bilateral Babinski's signs. Laboratory examination revealed slight liver dysfunction with minimal GPT and moderate gamma-GTP elevation. Examination of serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis. Though bilateral Babinski's signs disappeared after the abstinence from heavy drinking, ataxic gait and hyperreflexia of the lower extremities have continued. Alcoholic myelopathy without hepatic cirrhosis was rarely reported. In the relation of alcoholic cerebellar degeneration to alcoholic myelopathy, our cases are interesting and important. PMID- 8476669 TI - [Unusual CT and MRI appearance of the epidermoid tumor--a case report]. AB - We reported a case of epidermoid tumor with unusual findings on CT and MRI. A 41 year old woman was admitted because of headache. On admission she had no neurological deficits. CT revealed a lobular homogenous high-dense mass with a sharp margin in the mid-portion of the posterior fossa. The mass was shown as a low signal intensity on both T1- and T2-weighted MRI. An encapsulated mass containing "motor oil" like viscid fluid was removed by surgical operation. Histological examination revealed epidermoid cyst. CT-dense epidermoid tumor was discussed with referring to the literature. PMID- 8476670 TI - [A case of transtentorial upward herniation due to cerebellar infarction manifesting upward gaze palsy as an initial sign]. AB - Transtentorial upward herniation is a rare complication of cerebellar infarction and its development indicates an emergency and necessity of posterior cranial fossa decompression. A 63-year-old man with a history of myocardial infarction was admitted to the hospital complaining of sudden onset of vertigo and headache. Neurological examination revealed marked upward gaze palsy, right blepharoptosis, facial weakness, hearing loss on the left side and ataxia of the left upper and lower extremities. A few hours later, he rapidly lost consciousness and MRI revealed massive infarction in the left cerebellar hemisphere and transtentorial upward herniation. Immediate surgical decompression of the posterior cranial fossa was performed, thereafter patient gradually improved. This case suggests that upward gaze palsy is an important initial sign of transtentorial upward herniation with massive cerebellar infarction. PMID- 8476672 TI - The technical matter of product standards. PMID- 8476673 TI - Mike Grace talks to Geoff Garnett. PMID- 8476671 TI - [A 24-year-old man presenting Garcin syndrome and paraplegia]. AB - We report a 24-year-old man who presented unilateral multiple cranial nerve involvements followed by progressive paraplegia. The patient expired after developing DIC and pneumonia. Post-mortem examination revealed Ewing's sarcoma originated in the pubic bone with extensive metastases including the clivus which was responsible for his cranial nerve lesions. The patient was well until 24 years of age when he noted an onset of pain and a mass in the pubic region. The histology of the biopsy specimen of the tumor suggested Ewing's sarcoma. He was treated with chemotherapy and local radiation. A year after, he noted an onset of nuchal pain, difficulty in tongue movement, dysarthria, deafness in the left ear, and diplopia. On admission to our hospital in July 1990, neurological examination revealed an alert and intelligent Japanese male in no acute distress. The olfactory to the trigeminal nerves appeared intact. He showed complete abducens nerve palsy, facial weakness, mild deafness, and weakness of the soft palate, the sternocleidomastoid muscle and the tongue, all on the left side. The remainder of the neurological examination was unremarkable except for dysesthesia along the left C8 and Th1 dermatoms. Radiological examination revealed a 10 x 10 cm sclerotic mass in the public bone and a high signal mass lesion between the clivus and the pons in the T2-weighted MRI. His clinical course was complicated by acute paraplegia with anesthesia below the Th4 dermatom, DIC, and respiratory distress due to plural effusion. Post-mortem examination revealed a necrotic and hemorrhagic tumor in the pubic bone. The histology was consistent with Ewing's sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476674 TI - Putting the pilot scheme into practice. AB - If we accept that in the future audit is going to be a fact of life and the probability is that optional schemes will, in time, be replaced by compulsory participation, then input by general practitioners at this pilot stage should be a good investment for the future. PMID- 8476675 TI - 'A survey of disease changes observed on dental panoramic tomographs taken of patients attending a periodontology clinic'. PMID- 8476677 TI - 'Rampant caries--a new threat?'. PMID- 8476676 TI - 'Dentist provided the best third molar service'. PMID- 8476678 TI - Single dose instructions. PMID- 8476679 TI - 'Freedom of choice'. PMID- 8476680 TI - Specialist practice for minor oral surgery: a comparative audit of third molar surgery. AB - Cost efficiency of removing third molars in a practice specialising in minor oral surgery was compared to that of a hospital oral surgery department. A total of 100 patients treated in each locality were prospectively audited during the financial year 1989-90. Surgical complexity, waiting time, complications and patient satisfaction were compared. The hospital cases were costed individually and compared to fees received for the patients treated in the practice. The practice fees were also compared to average expenses as assessed by the Dental Rates Study Group Inland Revenue Enquiry. Patients were treated more promptly and at a lower cost in the specialist practice with no adverse effect on quality as assessed by complications and patient satisfaction. Surgical complexity was not a contraindication to practice treatment but some patients may be better treated in hospital because of medical or social circumstances. Patient charges for treatment carried out under General Dental Service regulations are a serious impediment to the viability of a specialist oral surgery practice. PMID- 8476681 TI - Complete denture prescription--an audit of performance. AB - The quality of clinical records obtained during the various stages of complete denture construction was assessed in a survey conducted in five large dental laboratories in 1989. The most common fault in approximately half of 188 upper and 158 lower impressions was overextension in the labial and buccal sulci. Of the 87 occlusal records examined, the rims indicated the intended incisal relationship in about 50% of cases. The border of the eventual denture was defined by the technician rather than by the dentist in most instances. The post dam was prescribed by the dentist in only 16% of the 50 trial dentures inspected. It is argued that a major cause of the lack of prescription is the level of the NHS fee, coupled with the fact that the laboratory expenses are deducted from that fee. PMID- 8476682 TI - Criterion based audit in prosthetic dentistry. AB - A criterion based retrospective audit into the provision of complete dentures in an undergraduate teaching programme has been produced. This consisted of a series of questions related to the treatment of the patient and the satisfaction or otherwise expressed about the treatment. The audit revealed where treatment had been successful according to the established criteria. It has been found that an audit of this nature is demanding of clinicians' time but does show where improvements can be made in patient management which will result in better health care. Clinical audit is now recognized as forming an important part of health care. It is applicable to all areas of dentistry, ie general dental practice, the community dental services and the hospital services, and to all specialities eg prosthetics, orthodontics etc. An audit programme needs careful planning and a pilot study is worthwhile to indicate areas of difficulty. This audit has been used in an undergraduate training programme, however, the process by which the audit has been assembled is an example of how an audit could be established in any area of dentistry, provided that the criteria are modified to make them relevant to the clinical speciality. PMID- 8476683 TI - The first 100 cases: a personal audit of orthodontic treatment assessed by the PAR (peer assessment rating) index. AB - The first 100 consecutively started cases treated by a specialist registrar in orthodontics were examined and pre- and post-study models were scored using the peer assessment rating (PAR) index. The PAR index proved both simple and reproducible to use: 92 cases had post-treatment records available, 91 patients registered a drop in PAR score, and one patient registered an increase. Of these 92 patients, 38 (41%) were greatly improved, 43 (47%) were improved, and 11 (12%) were made worse or no different (ie they failed to achieve a 30% drop in PAR score). Of the factors examined, only the appliance type used was significantly related to PAR score change. Of the 11 cases apparently made worse, individual examination revealed that four of these represented beneficial occlusal changes but due to limited treatment goals they did not register as improved using the PAR index according to previously agreed criteria. The PAR index measures 'good tooth position' which, although very important, is not the only factor in orthodontic treatment. The use of the PAR index to detect 'good' and 'bad' orthodontic treatment is not without problems. Its use in mixed dentition and adjunctive orthodontic treatments may not always be appropriate. PMID- 8476684 TI - What is BS5750? PMID- 8476685 TI - [The international in nursing. Nursing home with foreign nurses]. PMID- 8476686 TI - [The international in nursing. Health education crosses cultural barriers]. PMID- 8476687 TI - [The international in nursing. Swedish nursing education]. PMID- 8476688 TI - [The international in nursing. Master's Degree in the USA?]. PMID- 8476689 TI - [The international in nursing. Study trip to Canada]. PMID- 8476690 TI - [The international in nursing. When nurses are immigrants]. PMID- 8476691 TI - [The international in nursing. Minimum data-set for nursing]. PMID- 8476692 TI - [Prisoner inmates in the security department--observation and report]. PMID- 8476693 TI - [Meaningful and interesting work]. PMID- 8476694 TI - [Self-esteem--necessary for nursing competence!]. PMID- 8476696 TI - [Cetiprin tablets: a model preparation?]. PMID- 8476695 TI - [Home nursing--two nursing cultures in open health care]. PMID- 8476697 TI - [Work environment--why do things move so slowly in the health sector?]. PMID- 8476698 TI - [My childbirth experience]. PMID- 8476699 TI - [The international in nursing. Unequal cultures and traditions]. PMID- 8476700 TI - Synthesis and application of N,N-bis-(1-adamantyloxycarbonyl) amino acids. AB - The preparation of novel bis-(1-adamantyloxycarbonyl) amino acid derivatives has been undertaken and their properties studied. Among them, the p-nitrophenyl esters were subsequently applied to the stepwise synthesis of Leu-enkephalin. In the last coupling step, some hydantoin formation was encountered but it could be nearly completely overcome by working with more concentrated solution. The preparation of a tyrosine derivative presented special problems owing to the existence of the phenolic group in the precursor. The relative stability of 1 adamantyloxycarbonyl as N- and O-protecting groups was also studied. PMID- 8476702 TI - Prognostication in children with renal disease--with emphasis on IgA nephropathy. PMID- 8476701 TI - Follow-up of renal function and urinary protein excretion in childhood IgA nephropathy. AB - Renal haemodynamics and urinary protein excretion (UPE) were investigated in 36 patients with IgA nephropathy more than 3 years after renal biopsy (mean interval 6.3 +/- 0.5 years). At follow-up, 39% of patients had a reduced glomerular filtration rate (GFR) and 11% endstage renal failure. Twenty-five percent had albuminuria, and a further 25% microalbuminuria. All albuminuric patients had GFRs below the mean, and 78% of the albuminurics had a reduced GFR. However, non albuminurics also had decreased GFRs and GFR tended to fall with the duration of the disease in this group of patients. On comparing the histological changes in the biopsies with haemodynamic and UPE studies performed 6 years later, we found significant correlations between the extent of segmental glomerular sclerosis and GFR, effective renal plasma flow, urinary albumin and IgG excretion, respectively. Histological grading correlated with the same variables. Of the 4 uraemic patients, 2 were nephrotic at presentation, while the other 2 had a nephritic onset of disease and later developed heavy proteinuria. Three of their biopsies showed > or = 10% segmental glomerulosclerosis. Juvenile IgA nephropathy is not a harmless disease. Our results indicate that these children should be carefully monitored with adequate GFR measurements and urine protein analyses. PMID- 8476703 TI - Maintenance immunosuppression therapy and outcome of renal transplantation in North American children--a report of the North American Pediatric Renal Transplant Cooperative Study. AB - The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant, we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants. PMID- 8476704 TI - Correlation of ultrasound and renal scintigraphy in children with unilateral hydronephrosis in primary workup. AB - Ultrasound accurately detects hydronephrosis in infants and children, while nuclear medicine techniques quantify relative renal function in addition to characterizing the urodynamic relevance of hydronephrosis. This prospective study was undertaken to examine the relationship between ultrasound morphological findings and relative renal function, quantified with dynamic 99mtechnetium mercaptotriacetylglycine imaging, in the initial diagnostic workup of children with unilateral hydronephrosis. The ultrasound grade of hydronephrosis and relative renal function ipsilateral to the hydronephrosis were inversely related, indicating that with more severe hydronephrosis ultrasound fails to estimate the potential reduction of relative kidney function. Because renal function is not necessarily affected by hydronephrosis, renal scintigraphy is indicated to assess the functional status of hydronephrotic kidneys. PMID- 8476705 TI - IgG and IgA classes of anti-neutrophil cytoplasmic autoantibodies in a 13-year old girl with recurrent Henoch-Schonlein purpura. AB - We describe a 13-year-old girl with recurrent Henoch-Schonlein purpura whose symptoms were precipitated by upper respiratory tract infections. Her serum was positive for both IgG and IgA classes of anti-neutrophil cytoplasmic autoantibodies by immunofluorescence. The titers of both autoantibodies correlated with disease activity. The immunopathology underlying these findings is discussed. PMID- 8476706 TI - What is the current recommendation in the management of covert (significant) bacteriuria in infants and preschool children? PMID- 8476707 TI - Acute noncrescentic poststreptococcal glomerulonephritis presenting with pulmonary hemorrhage. AB - We report a child with acute poststreptococcal noncrescentic glomerulonephritis and pulmonary hemorrhage. This patient demonstrates that: (1) poststreptococcal noncrescentic glomerulonephritis in children can be associated with pulmonary hemorrhage, (2) an expeditious renal biopsy in patients with acute or rapidly progressive glomerulonephritis and pulmonary hemorrhage can establish an early diagnosis and provide timely guidance for treatment, and (3) although not proven by controlled studies, the intravenous administration of methylprednisolone in our patient may have been effective in the treatment of pulmonary hemorrhage. PMID- 8476708 TI - Persistent microscopic haematuria without proteinuria. PMID- 8476709 TI - Body growth in urinary tract malformations. AB - Body height and height velocity were analysed in 54 children with obstructive urinary tract malformations over a mean period of 8.7 years, using new auxological methods. At the time of diagnosis, 9% of patients had a height of more than 2 standard deviations below the normal mean. Mean relative height changed significantly from the first to the last observation, the standard deviation score (SDS) increasing from -0.16 to +0.36 in patients with hydronephrosis compared with normal children (P < 0.05) and from -0.63 to +0.02 SDS in those without hydronephrosis (P < 0.005). The pathogenesis of the described growth disturbance is not clear. Stepwise multiple regression analysis pointed to a possible link between the duration of antibiotic treatment and the recovery of growth capacity, but improved growth could not clearly be attributed to any medical or surgical treatment. The synchronized average growth velocity curve was similar to that of healthy children and showed a normal pubertal spurt. Final height and target height calculated from parents' height differed only slightly from that of the normal population. PMID- 8476710 TI - Alport's syndrome and hereditary motor and sensory neuropathy type I--an unfortunate coincidence. AB - A 15-year-old boy with Alport's syndrome and hereditary motor and sensory neuropathy type I is described. An association between hereditary motor and sensory neuropathy and a nephropathy has been reported in 12 cases in the literature. Although showing features in common with Alport's syndrome and with a familial tendency, these 12 cases are clinically and histologically distinct from our patient who is the unfortunate inheritor of two genetic disorders, one maternally and one paternally derived. Recognition of an association between nephropathy and neuropathy, although rare, is important. PMID- 8476711 TI - Hypercholesterolemia in children with cystinosis. AB - Ten children with cystinosis had their diet, serum creatinine, and total cholesterol (averaged in 6-month blocks and normalized by calculating a z score (TCz)] monitored for a mean of 5 years. The TCz scores were elevated in boys (P < 0.01) but not girls (P = 0.67). The boys had elevated TCz scores for 58% of their 29 pre-transplantation years of follow-up, rising as early as 1 year of age at a mean rate of 0.67 standard deviations per year. Cystinotic boys had higher TCz scores than children with other tubular disorders (P < 0.025). All 4 cystinotic boys who developed renal insufficiency had a rise in TCz scores at a rate greater than control children with comparable renal impairment. Two cystinotic boys received a renal transplant; subsequent TCz scores were markedly lower, but remained elevated. The nutritional status of cystinotic children deteriorates after 3 years of age: they have decreased fat stores, elevated TCz scores and consume high fat diets insufficient in total calories. In summary, cystinotic boys have marked, progressive hypercholesterolemia which improves after renal transplantation. PMID- 8476712 TI - Renal and biliary abnormalities in a new murine model of autosomal recessive polycystic kidney disease. AB - Current models of autosomal recessive polycystic kidney disease (ARPKD) fail to demonstrate biliary abnormalities in association with renal cysts. We therefore studied a new murine model of ARPKD in which dual renal tubular and biliary epithelial abnormalities are present. Affected homozygous animals typically die 1 month postnatally in renal failure with progressively enlarged kidneys. Renal cysts shift in site from inner cortical proximal tubules at birth to collecting tubules 20 days later, as determined by segment-specific lectin binding. Increased numbers of mitosis were demonstrated in proximal and collecting tubular cysts. In addition, epithelial hyperplasia was demonstrated morphometrically in the intra- and extrahepatic biliary tract of affected animals. The number of intrahepatic biliary epithelial cells was increased by 50% on postnatal day 5 and by 100% on postnatal day 25 (P < 0.01). Despite an increased frequency of "chaotic" portal areas in mice with renal cysts, no intrahepatic cysts or shape abnormalities of the biliary lumen were detected using biliary casts and morphometry. Additionally there was nonobstructive hyperplastic dilatation of the extrahepatic biliary tract which was linked in all animals to the presence of renal cysts. The hyperplastic abnormalities in both renal and biliary epithelium make this new mouse strain a good model for the study of the dual organ cellular pathophysiology of ARPKD. PMID- 8476713 TI - Growth of uremic infants on forced feeding regimens. AB - Infants born with congenital renal insufficiency generally grow poorly during the first years of life and incur a height deficit that is rarely regained. Actual energy and protein requirements have not been determined for these children. In 12 infants with creatinine clearances less than 70 ml/min per 1.73 m2, growth and nutrient intakes were monitored during the first 2 years of life. Forced feeding regimens after 3 months of age, including gastrostomy in 3 patients, were necessary to maintain energy intakes near 100% of the recommended dietary allowance (RDA). Protein intakes averaged in excess of 140% RDA. Linear growth did not correlate with either energy or protein intakes, suggesting that neither was a limiting factor to growth. Length velocity standard deviation score (LV SDS) did not correlate with degree of renal insufficiency at any age, but average LV-SDS did relate significantly and inversely to C-terminal parathyroid hormone (PTH) levels. Growth parameters, including LV-SDS and weight velocity SDS (WV SDS) were lowest at 6 months of age. Weight and length SDS followed with a maximum decline at 12 months of age. While weight for length SDS remained normal and WV-SDS showed recovery during the 2nd year, LV-SDS remained negative. Length SDS stabilized near--2 SDS. In summary, these data suggest that the major height deficit in infants with renal insufficiency is incurred during the first 6 months of life. Ponderal indices suggested that very early nutritional deficits may have been a primary contributor to subsequent height deficits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476714 TI - Aminoglycoside ototoxicity in pediatric patients receiving long-term peritoneal dialysis. AB - We evaluated 14 children on long-term peritoneal dialysis for ototoxicity associated with aminoglycoside (AG) therapy. Baseline evaluation of all patients and 7 controls included pure-tone audiometry (PTA) and click-evoked auditory brain stem response (ABR). Nine patients had repeat PTA and ABR evaluations and vestibular testing 1 year after study entry. Five patients had an additional assessment following intraperitoneal AG therapy. The baseline auditory function of the patients was significantly poorer than controls at 6.0 and 8.0 kHz by PTA (P < 0.05), whereas the results of ABR testing were not different. Of the 14 patients, 4 (28%) had hearing loss, 3 of whom had a history of intravenous AG therapy. In contrast, none of the patients who received intraperitoneal AG therapy only, or without a history of AG therapy, had hearing loss (P < 0.005). There was no evidence of progressive loss of hearing acuity with time or associated with intraperitoneal AG therapy. One patient had findings of vestibular dysfunction. We conclude that children receiving peritoneal dialysis are at risk of AG ototoxicity. While intraperitoneal administration of AG may be associated with less ototoxicity than intravenous administration, further study is necessary to verify this finding and close monitoring of AG levels remains mandatory irrespective of the route of administration. PTA rather than click evoked ABR appears to be the best indicator of abnormal hearing acuity in this population. PMID- 8476715 TI - Disodium ethylenediaminetetraacetate: adverse effects in dialyzed children. AB - The present report describes untoward effects of disodium ethylenediaminetetraacetate (EDTA) in three of six pediatric patients treated with continuous cycling peritoneal dialysis, in whom this agent was infused intravenously to lower serum ionized calcium levels during dynamic testing of parathyroid gland function. Patients developed an influenza-like syndrome characterized by fever rhinorrhea, cough, sneezing, and lacrimation. All symptoms disappeared within 24 h. A similar degree of hypocalcemia was induced with sodium citrate, an alternative hypocalcemic agent, in the same patients without side effects. Sodium citrate, rather than EDTA, should be used to induce hypocalcemia when assessing parathyroid gland dynamics in children with end-stage renal disease. PMID- 8476716 TI - Social support, family variables, and compliance in renal transplant children. AB - The relationship between family functioning, social support, and medication compliance in 32 renal transplant children and their parents was examined. Results indicated that children whose fathers gave more emotional support or were more informative were less compliant with azathioprine and cyclosporine (P < 0.05 for both). Children from families experiencing numerous stresses were also found to be less compliant with azathioprine (P < 0.05). Finally, compared with older children, younger children were found to be less compliant with cyclosporine (P < 0.005). Implications for predicting child adherence and for future research relating to compliance with multidrug regimens are discussed. PMID- 8476717 TI - Operating characteristics of pediatric continuous arteriovenous hemofiltration in an animal model. AB - Continuous arteriovenous hemofiltration (CAVH) is an increasingly popular technique in the care of critically ill children. The operating characteristics of the available circuits are largely unknown. Prior to introducing CAVH into our pediatric intensive care unit, we investigated the performance of three CAVH circuits: CAVH with postfilter dilution, CAVH with prefilter dilution (CAVHpre) and CAVH with dialysis counterflow. Using a neonatal lamb model, we measured filter blood flow (QB), ultrafiltrate rate (QU), arterial, venous and ultrafiltrate compartment pressures, oncotic pressure, plus urea levels in blood and ultrafiltrate fluid for the three CAVH circuit designs. Transmembrane pressure and urea clearance were calculated for various values of QB after varying a clamp on the arterial side of the circuit. The major finding, applicable to all circuits, was the wide variability of QB. Constant attention was required in order to obtain a consistent QB. Fluid clearance was effective with all three circuits. Urea clearance averaged 5-10 ml/min and was principally dependent on QU and independent of QB. The addition of dialysis counterflow did not increase urea clearance. The most convenient circuit we tested was CAVHpre, but the problem of unstable QB is common to all unpumped arteriovenous filtrate circuits. It is a major limiting factor in the practical application of this technology to critically ill children. PMID- 8476718 TI - Cerebral vasculitis in acute post-streptococcal glomerulonephritis. AB - Neurological complications in acute post-streptococcal glomerulonephritis (APSGN) have been traditionally attributed to hypertensive encephalopathy. A 9-year-old girl with biopsy-documented APSGN developed seizures at a time she was normotensive and biochemically well balanced. Computed tomography of her brain was consistent with vasculitis, a finding which was also clinically supported by apparent vasculitic involvement of other organ systems. All clinical, laboratory and radiological abnormalities resolved with recovery from the APSGN. We suggest that on rare occasions neurological complications in APSGN may result from involvement of the central nervous system in multiorgan transient vasculitis. PMID- 8476720 TI - Relapsing gross haematuria in Munchausen syndrome. AB - A 10-year-old female with relapsing gross haematuria and Munchausen syndrome is reported, emphasizing the rarity of this situation in children and the difficult diagnostic pathway. A careful personality study of the patient and family members is absolutely necessary in order to proceed with diagnosis and successful treatment. PMID- 8476719 TI - Treatment with a combination of low-density lipoprotein aphaeresis and pravastatin of a patient with drug-resistant nephrotic syndrome due to focal segmental glomerulosclerosis. AB - Results of recent animal studies have lent support to the hypothesis that hyperlipidaemia may contribute to renal injury. This report documents the case of a 15-year-old boy with drug-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FGS) who showed an improvement in renal function and proteinuria as a result of treatment with low-density lipoprotein aphaeresis (LDL A) combined with pravastatin. Although further work is required to determine the efficacy of lipid-lowering therapy in progressive glomerular disease in humans, the combination of LDL-A and pravastatin is likely be included in the choice of treatment modalities available for patients with drug-resistant nephrotic syndrome due to FGS. PMID- 8476721 TI - Masking of physicians in the Growth Failure in Children with Renal Diseases Clinical Trial. AB - Masking--hiding identities of treatments from the patient, physician and/or statistician--is a critical element in clinical trials. Wherever possible, masking is implemented to eliminate observational bias or systematic error. In this paper, general concepts of masking in clinical trials are examined. Specific masking procedures used in the "Growth Failure in Children with Renal Diseases" (GFRD) Clinical Trial are described. A method to evaluate the "success" of this masking procedure for physicians is introduced. For each randomized patient at each clinical center, the clinic director was asked to predict which treatment (1,25-dihydroxyvitamin D3 or dihydrotachysterol) was assigned. Results showed that 72% of responses initially indicated "absolutely no idea" of treatment. Additional analyses revealed that the number and percentage of "correct" guesses were essentially equal for the two treatment groups and that a patient's time on treatment did not affect the mask. We conclude that the mask of physicians in the GFRD Clinical Trial was well maintained. PMID- 8476722 TI - Management of primary hyperoxaluria: efficacy of oral citrate administration. AB - The prognosis of primary hyperoxaluria (PH) is not only related to endogenous oxalate production and the response (if any) to pyridoxine (in type I), but is greatly influenced by extrarenal factors like dehydration. The earlier the diagnosis of PH, the better the chances of improving the prognosis in individual patients. Measures to enhance the solubility of calcium oxalate are important. Besides ensuring at all times a generous fluid intake (> 2 l/m2), administration of alkali citrate (0.15 g/kg), which has not been advocated so far in PH, appears very promising. We studied the effect of sodium citrate in six patients with PH. Mean urinary citrate excretion (mmol/day per 1.73 m2) without oral citrate was very low (0.57) and rose to 2.49 with citrate administration. This was accompanied by a significant decrease in the calcium oxalate saturation (calculated by equil 2) from 11.7 to 6.9 (P < 0.05). Treatment in five patients over 10-36 months resulted in improved (1) or stabilized (4) renal function and reduced passage of stones. Additional measures include restriction of salt and of oxalate-rich food. We conclude that long-term administration of alkali citrate is beneficial in patients with PH. PMID- 8476723 TI - Should liver transplantation be performed before advanced renal insufficiency in primary hyperoxaluria type 1? AB - Primary hyperoxaluria type 1 (PH1) is a rare recessive autosomal inborn error of glyoxylate metabolism leading to oxalate retention, the first target of which is the kidney. The disease is caused by a defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase. Patients with pyridoxine-resistant forms of PH1 usually require organ replacement therapy, i.e. liver transplantation to supply the deficient enzyme and/or kidney transplantation to replace the affected organ. The current experience of the management of PH1 has emphasized two main points: (1) end-stage renal failure must be avoided since it increases dramatically the risk of systemic involvement, (2) the correction of oxalate overproduction and organ overload requires the removal of the host liver. Practical attitudes towards these ideas are difficult to assess and an individualized strategy is therefore required. Isolated kidney transplantation should be limited to adult patients with late-onset and a mild course of the disease. The present experience of combined liver-kidney transplantation was gained mainly in adult patients with severe systemic involvement; the 3-year patient survival rate recently increased to 82%. This figure might be improved if the procedure were performed earlier while the glomerular filtration rate (GFR) is above 25 ml/min per 1.73 m2. Isolated liver transplantation should be considered in carefully selected children with severe forms of pyridoxine resistance (PH1) before GFR has dropped to less than 30 ml/min per 1.73 m2; it seems to be indicated especially in the presence of a rapid decline of GFR in the preceding year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476724 TI - Human immunodeficiency virus nephropathy. AB - Varying components of the syndrome of human immunodeficiency virus nephropathy (HIVN) have been described, the most pertinent including proteinuria/nephrotic syndrome, progressive azotemia, normal blood pressure, enlarged and hyperechoic kidneys, rapid progression to end-stage renal disease (ESRD), and no response to treatment regimens. The diagnosis of HIVN requires identification of excessive proteinuria or albuminuria, determined by a total protein excretion on a timed urine collection or a high protein/creatinine ratio in a random specimen. Various pathological lesions have been found in HIVN. The lesion of focal and segmental sclerosis (FS/FSS) is most characteristic in adults and usually is associated with a rapid demise. FS/FSS also has been described in approximately one-half of the pediatric patients reported in the literature (31/64). Despite progression to ESRD, the clinical course in children with HIVN is less fulminant than in adults. Other reported histological findings include primarily mesangial hyperplasia as well as minimal change, focal necrotizing glomerulonephritis or lupus nephritis, and hemolytic uremic syndrome. In addition to glomerular pathology, interstitial findings of dilated tubules filled with a unique proteinaceous material, atrophied tubular epithelium, and interstitial cell infiltration are very common. On electron microscopy, most investigators have found tubuloreticular inclusion bodies in endothelial cells of glomerular capillaries. Treatment of patients who develop ESRD remains highly controversial. Most adult patients treated with hemodialysis have succumbed rapidly; peritoneal dialysis has been better tolerated. Transplantation in patients with HIV infection must be considered to be tentative, with reports of acceleration towards full blown acquired immunodeficiency syndrome in some and uneventful 5-year survival in others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476726 TI - A 6-year-old black boy with fever and gross hematuria. Acute pyelonephritis. PMID- 8476725 TI - Complement and glomerulonephritis--an update. AB - The complement (C) system in man and its relationship to disease has been the subject of intensive research. In this review, we update the information concerning the nature of the various C components, and present some of the similarities between structure and function of the C components and their respective genes. The clinical problems which are encountered in individuals with acquired C abnormalities and with a genetically determined deficiency of a single component provide helpful clues to understanding the affected patients and the possible functional importance of the particular deficient component. The steady progress in identifying both normal variants of C components and the gene defects which produce C deficiencies offers the prospect of correlating structure of the C components with possible pathogenic roles in disease. Genetically determined C abnormalities are more commonly recognized during childhood. An appreciation of the basic aspects of the C system is a helpful tool for the pediatric nephrologist. PMID- 8476727 TI - Normal serum uric acid concentrations for age and sex and incidence of renal hypouricaemia in Japanese school children. PMID- 8476728 TI - Indomethacin treatment in children with daytime frequency micturition. PMID- 8476729 TI - Normal levels of urinary brush border antigens and other tubular markers in children. PMID- 8476730 TI - The immunology of scabies. AB - Individuals with scabies react to bites by generating a cell-mediated immune response at the bite site. This elicits a very itchy papule that is often excoriated. Sometimes ulcerated papules, vasculitis, and nodules develop as a result of other immunologic reactions in skin. Immunologic reactions mediated by antibodies of the immunoglobulin G (IgG), IgM, and especially, IgE classes may also be involved. None of these reactions have been shown to eliminate all mites from the skin surface, but locally these reactions may prevent the epidemic multiplication of scabies' organisms on the skin surface, as observed in some patients with crusted scabies. PMID- 8476731 TI - Scabies research: another dimension. AB - The life cycle of canine scabies has been studied extensively. Currently studies are focusing on mite behavior, physiological requirements, host specificity, mite survival, and clinical complications of scabies. Investigations are giving insight into immunologic responses to infestation and cross-reactivity with house dust mites. A diagnostic blood test or vaccine may become a future reality, if a unique antibody response can be isolated. Can scabies transmit the human immunodeficiency virus (HIV)? This controversial area needs prompt definitive exploration. PMID- 8476732 TI - Delusions of parasitosis. AB - The fixed belief that one is infested with living organisms, in the absence of any objective evidence that such infestation exists, is termed "delusions of parasitosis." For most patients, this is a "monosymptomatic" disorder because there is no evidence of psychotic ideation in other areas of their lives. This overall normality of thought processes, together with exceptional strength of conviction regarding infestation, makes confirmation of a suspected diagnosis difficult. We want, and need, to be certain that a true infestation is not missed. This requires careful history taking, thorough examination of the skin, microscopic review of the material brought in by the patient and, occasionally, biopsy of lesions identified by the patient as "bite" sites. Establishment of a diagnosis is difficult enough, but it is even more difficult (usually impossible) to convince the patient that there are no "bugs" present. Attempts to have the patient visit a psychiatrist are virtually always rebuffed, leaving the clinician no choice but to begin therapy. Pimozide, a blocker of dopamine receptors, represents the pharmacological treatment of choice. The use of this drug is usually quite helpful, but relapse frequently occurs when treatment is stopped. For patients who will not take the drug, and for those who fail treatment, the best that can generally be achieved is the provision of a supportive environment. In such a setting, many of these patients eventually shift to a less troublesome chronic phase of their disease during which the delusion partially or even completely slips into the subconsciousness thus allowing for more normal daily functioning. PMID- 8476733 TI - Mite infestations other than scabies. AB - Scabies is clearly the primary medical problem involving mites. However, regionally, there is a broad variety of other dermatoses associated with mite exposure, which in some areas vastly exceed the incidence of scabies. Also, scabies is characterized by a cyclical occurrence that is unusual in other mite infestations and mite-associated dermatoses. Many of these have seasonal or regional characteristics, which will be discussed. The clinical aspects of mite infestation will primarily be dealt with, and the basic anatomy and biology of the mites will be ignored. PMID- 8476734 TI - Papular urticaria. AB - The diagnosis of papular urticaria has evolved over the years and has many synonyms. Its most common present day usage relates to a cutaneous reaction presumably from an apparent exposure to insects. The evolving science in this area is allowing a better understanding of potential sources including newer tools to look at antigens from insect proteins injected after bites from flying insects and some other environmental arthropods. Insight to etiology is important and can be partially determined by clinical history and clinical pattern of symptoms. The usual approach in practice is to treat symptomatically first while investigating etiologies. Increasing appreciation of the role of environmental mites and ectoparasites has allowed us more precision in diagnosis to specifically treat the cause. The primary challenge in therapy often relates to the achievement of the goal of symptom relief. This is often difficult because of the chronicity of the syndrome when the patient is seen by a specialist. Both the search for etiology and symptomatic relief often need to be aggressive to achieve the desired therapeutic benefit for the patient. PMID- 8476735 TI - Zoonoses of dermatological interest. AB - The zoonoses are those diseases transmitted from animals to humans. Although commonly thought to be infectious in origin such as scabies or dermatophytosis, inflammatory processes may also be zoonotic. Contact dermatitis may result from allergens being carried from animals to humans. Although the scabies mite is somewhat species specific, various mites sometimes have the opportunity of producing skin disease on man (ie, canine scabies, porcine scabies, and feline scabies [notoedric mange]); cheyletiellosis is caused by a similar mite, often found in rabbits. The index case of superficial fungal infections may be the household pet, whereas the cause of flea bite dermatitis (papular urticaria) may be the lack of an animal, resulting in the flea choosing a human for feeding. Understanding zoonotic skin diseases will improve the clinician's diagnostic skills. Both the human and animal patient will then receive more effective treatment in a quicker fashion. PMID- 8476736 TI - Scabies in AIDS. AB - Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) will be the most common disease triggering crusted (Norwegian) scabies. Scabies should be suspected in any atypical itching (or non) rash in HIV/AIDS patients. Attempt to prove the diagnosis by doing a skin scraping, or if negative, a skin biopsy. Unusual forms of scabies in HIV/AIDS can be divided into crusted scabies and atypical (exaggerated) scabies. Therapy requires the sequential use of scabicides, usually over a longer period than is required to clear an ordinary case of scabies. Compliance is a concern, and the scabicides are best administered under supervision whenever possible. Isolating the index patient and treating the environment of patients with crusted or atypical scabies is much more significant than in ordinary scabies. The transmission in hospitals of ordinary scabies from an index patient with crusted scabies to other patients, health care workers, etc, is common. Protective measures and early diagnosis and therapy are essential. PMID- 8476737 TI - Global health situation. V). Noncommunicable diseases, disability. PMID- 8476738 TI - Potentiation of the pressor response to stress by tolbutamide in dogs. AB - Tolbutamide has previously been shown to amplify the pressor effects of "exogenous" catecholamines in conscious dogs, possibly due to sensitization of the alpha 1-adrenoreceptor-mediated vasoconstriction. The objective of this study was to examine if tolbutamide also amplifies the pressor effects of "endogenous" catecholamines released during psychological stress (classical Pavlovian aversive conditioning). Experiments were conducted in beta-adrenoreceptor-blocked (propranolol, 1 mg/kg, i.v.) conscious dogs (n = 4) trained in classical aversive conditioning. Conditioning was accomplished by following a tone (CS+) with a 1/2 second shock; another tone (CS-) was not followed by any shock and served as control. With saline pretreatment, aversive conditioning (i.e., CS+) increased mean arterial pressure (MAP) only by approximately 4.7% when compared to CS-, whereas with tolbutamide (45 mg/kg, i.v.) pretreatment, the increase in MAP induced by CS+ beyond what was induced by the CS- (approximately 6.2%) was significantly (p < 0.05) larger than that with saline pretreatment. In isolated canine femoral arterial segments (n = 4), the vasoconstrictor effect of phenylephrine (an alpha 1-agonist) at 5 x 10(-6) M (which was the EC50 value) was amplified by 2 x 10(-2) M of tolbutamide from 54.0 +/- 2.0% to 66.9 +/- 2.1%. In conclusion, tolbutamide amplifies the pressor effects of "endogenous" catecholamines in conscious dogs, possibly by sensitization of the alpha 1 adrenoreceptor-mediated vasoconstriction. This mechanism of action is novel and has not been reported with other agents. PMID- 8476739 TI - Pavlovian conditioning in human skilled motor behavior. AB - The role of Pavlovian contingencies in human skilled motor behavior was investigated in three experiments by means of a new conditioning preparation. In Experiment 1 the present method was shown to be appropriate for the study of associative learning. Subjects who experienced a standard delay configuration performed significantly more conditioned responses than subjects who received either backward conditioning or random pairings. Stimulus generalization was shown to be slight in two additional groups. Subsequent experiments examined conditioning with multiple conditioned stimuli (CSs). In particular, in Experiment 2 some reciprocal overshadowing was demonstrated when two conditional stimuli (tone and vibration) were compounded. Experiment 3 investigated blocking. Blocking was less than expected, however. Subjects' perceptions of the stimuli and reaction time data suggest that a certain proportion had shifted their attention to the added element of the CS compound. Results are discussed in relation to other studies on Pavlovian learning in humans and animals, which are concerned with "stimulus selection." PMID- 8476740 TI - Effects of transient coronary artery occlusion on canine intrinsic cardiac neuronal activity. PMID- 8476741 TI - Acute versus chronic post-traumatic stress disorder. AB - A photographic lens and filter model is presented which outlines six steps between a person's perception of stressful life events and their possible eventual development of an illness. Persons developing acute post-traumatic stress disorder differ markedly in their processing of early steps in the model compared to those who go on to suffer from chronic post-traumatic stress disorder. Persons with the acute disorder, with high likelihood of recovery, generally have had enriching early life experiences, use psychological defenses to a moderate degree, and demonstrate ample coping capabilities. Those going on to the chronic disorder, who frequently don't recover, often report impoverished early life experiences, employ psychological defenses to an extreme degree, and show a paucity of coping skills. These differences are illustrated by histories from survivors of a terrorist bombing and by observations made by the author of returned prisoners of war and civilian hostages. PMID- 8476742 TI - Effects of transient coronary artery occlusion on canine intrinsic cardiac neuronal activity. AB - In order to further elucidate the regulatory function of canine epicardial neurons, the effects of transient coronary artery occlusion on their spontaneous activity was studied. Fifty-eight individual, spontaneously active units were identified by means of their action potential configurations in specific loci of atrial and ventricular epicardial fat of 10 anesthetized dogs. The activity of 49 of the units was modified by one minute of coronary artery occlusion. Twenty-four of the 49 responding units exhibited increased activity and 37 decreased activity during coronary artery occlusions. Activity changes were sometimes, but not always, associated with decreased left ventricular intramyocardial systolic pressure. During reperfusion, the activity of 6 units was increased compared to control levels, even though ventricular pressures remained the same. Following acute decentralization, 48% of previously active units generated spontaneous activity; the activity of 89% of these was altered during coronary artery occlusion despite the fact that overall cardiodynamics were unchanged. Following hexamethonium administration, the activity generated by 9 of 10 spontaneously active units was modified by coronary artery occlusion. It is concluded that transient coronary artery occlusion can modify the activity generated by intrinsic cardiac neurons, such modification involving central and peripheral neuronal interactions. PMID- 8476743 TI - A review of neuroendocrine and neurochemical changes associated with static and extremely low frequency electromagnetic field exposure. PMID- 8476744 TI - Hypothesis: the nasal fatigue reflex. AB - Natural selection results in adaptations. I suggest that unexplained fatigue may be an adaptive response to nasal impairment. For macrosmatic animals, intact olfaction is necessary to detect predators. In such animals, any reflex (e.g., fatigue) triggered by nasal dysfunction that limited exposure would offer great survival advantage. The "fatigued" animal would remain in its protected environment, unexposed to hungry carnivores, while the nose healed. In humans, clinical syndromes associated with unexplained fatigue (chronic fatigue syndrome, tension fatigue syndrome, allergic fatigue, neurasthenia, etc.) are characterized by symptoms that, in part, are nasal in origin. The older medical literature does describe the resolution of fatigue in neurasthenia after nasal treatments. Nasal reflexes in animals do cause significant systemic effects, including an inhibition of muscle action potentials that is, perhaps, analogous to the "heavy limbed" sensation of those with fatigue. Furthermore, reflexes similar to the one proposed do exist in humans: the diving reflex presumably served our amphibian ancestors well as an oxygen conserving technique with submersion, but serves no known useful function now. Other human nasopharyngeal reflexes with profound cardiovascular and systemic effects are well described but only occasionally studied. The proposed nasal fatigue reflex should be examined as a possible ancient adaptive response to nasal malfunction. PMID- 8476746 TI - Tissue-specific promoters regulate aromatase cytochrome P450 expression. AB - In the human, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory has indicated that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start-site. This promoter is not utilized in placenta but instead, the promoter used to drive aromatase expression in placenta is at least 40 kb upstream from the translational start-site. In addition, there is a minor promoter used in the expression of a small proportion of placental transcripts which is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues including placenta-related cells such as JEG-3 choriocarcinoma cells, hydatidiform moles, and other fetal tissues such as fetal liver. On the other hand, in adipose tissue expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5'-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start-site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical. PMID- 8476747 TI - Diverse mechanisms of control of aromatase gene expression. AB - The synthesis of estrogens from androgens is catalyzed by a microsomal cytochrome P450 termed aromatase (P450arom). The expression of this enzyme is highly regulated in both a developmental and cell-type specific fashion. We have chosen to examine the molecular basis of aromatase gene regulation by studying two models of aromatase expression: the Sebright bantam chicken and the R2C rat Leydig tumor cell line. In the first model, affected (Sebright) chickens express aromatase in many extragonadal tissues, while normal Leghorn chickens express aromatase only in the ovary and hypothalamus. Our studies have demonstrated that in normal chickens the site of transcription initiation is located approx. 147 nucleotides upstream of the initiator methionine. While Sebright animals also express aromatase mRNA initiated at an analogous initiation site in the ovary, a distinctive species of aromatase mRNA is also detected and is present in ovary and extragonadal tissues. This mRNA contains an identical coding sequence, but contains an alternatively spliced 5' noncoding exon that is derived from a distinctive promoter. The second model, the R2C Leydig tumor cell line, provides ample contrast. This cell line expresses high basal levels of aromatase (150-200 pmol/h/mg protein) that is suppressed with administration of 8 bromo cAMP or forskolin but the activity is not altered by glucocorticoids or epidermal growth factor treatment. Despite this distinctive pattern of regulation, at least three species of aromatase mRNA are detected in Northern blots, each of which is also detected in rat ovary. Primer extension and S1 nuclease assays indicate that both granulosa cells and R2C cells utilize a promoter that is located approx. 97 nucleotides upstream of the initiator methionine. These studies suggest that the "ovarian" promoter is evolutionarily conserved in both rats and chickens. These results further imply that the genetic mechanisms controlling the diversity of aromatase expression among tissues and among different species are likely to fall into two groups: those that employ distinctive promoters and alternative splicing and those that effect different patterns of regulation through a common ("ovarian") promoter. PMID- 8476748 TI - Structure-function studies of human aromatase. AB - Site-directed mutagenesis experiments have been carried out to determine the structure-function relationship of human aromatase. By sequence comparison, the region in aromatase that corresponds to the distal helix of cytochrome P-450cam has been identified to be Gln-298 to Val-313. Eight aromatase mutants with changes in this region, i.e. C299A, E302L, P308F, D309N, D309A, T310S, T310C, and S312C, have been generated using a mammalian cell stable-expression system. The results from site-directed mutagenesis studies indicate that the region containing Gln-298 to Val-313 is indeed a very important part of the active site of aromatase. The catalytic properties of P308F, D309N, and D309A have been examined in detail and are discussed. Active site-directed labeling is also an important approach to investigate the structure-function relationship of aromatase. HPLC-linked electrospray mass spectrometry is indicated as a useful technique for the characterization of active site-directed probe-modified enzyme. The mass spectral analysis of aromatase suggests that aromatase is glycosylated. PMID- 8476745 TI - The independent roles of diet and serum lipids in the 20th-century rise and decline of coronary heart disease mortality. AB - Risk factors are causally related to coronary heart disease (CHD), but in widely varying historic, geographic, socioeconomic, and individual relationships. Serum cholesterol is only one of many risk factors that, even when considered together in prospective studies, account for well under half of the CHD incidence. It is neither primarily regulated by the diet nor significantly related to it. Many findings discordant with widespread beliefs about a causal role of the diet in CHD are reviewed. It may be concluded that dietary fats are largely not responsible for relationships of serum cholesterol to CHD, or for its 20th century rise and decline. PMID- 8476749 TI - Steroidal inhibitors as chemical probes of the active site of aromatase. AB - Androstenedione analogs containing 7 alpha-substituents have proven to be potent inhibitors of aromatase in human placental microsomes, in MCF-7 mammary cell cultures, and in JAr choriocarcinoma cells. Recent investigations have focused on the use of mechanism-based inhibitors, such as 7 alpha-substituted 1,4 androstadienediones, to biochemically probe the active site of aromatase. Inhibition kinetics were determined under initial velocity conditions using purified human placental cytochrome P450arom protein in a reconstituted system. Derivatives of 1,4-androstadiene-3,17-dione and 1,4,6-androstatriene-3,17-dione exhibited high affinity in the purified enzyme system. 7 alpha-(4' Amino)phenylthio-1,4-androstadiene-3,17-dione, abbreviated 7 alpha-APTADD, demonstrated rapid time-dependent, first-order inactivation of reconstituted aromatase activity only in the presence of NADPH. The apparent Kinact for 7 alpha APTADD is 11.8 nM, the first-order rate of inactivation is 2.72 x 10(-3) sec-1, and the half-time of inactivation at infinite inhibitor concentration is 4.25 min. The values for the rate constant and half-time of inactivation are similar to those observed in the placental microsomal assay system. Further studies were performed with radioiodinated 7 alpha-(4'-iodo)phenylthio-1,4-androstadienedione, 7 alpha-IPTADD, and the reconstituted aromatase system. Incubations with [125I] 7 alpha-IPTADD were followed by protein precipitation, solvent extraction, and column chromatography. Analysis of the isolated cytochrome P450arom by gel electrophoresis and autoradiography demonstrated the presence of only one radioactive band, which corresponded to the protein staining band for cytochrome P450arom. HPLC radiochromatographic analysis of the isolated cytochrome P450aroM confirmed the presence of only one radioactive peak coeluting with the u.v. peak for cytochrome P450arom. Peptide mapping analysis by reverse-phase HPLC of digested inhibitor-cytochrome P450arom complex demonstrates that the radioactive inhibitor is covalently bound to a lipophilic fragment. In summary, these inhibitors produced enzyme-catalyzed inactivation of reconstituted aromatase activity, and radioiodinated 7 alpha-IP-TADD binds covalently to the cytochrome P450arom. PMID- 8476750 TI - Studies on the mechanism of aromatase and other cytochrome P450 mediated deformylation reactions. AB - Aromatase is a microsomal cytochrome P450 that converts androgens to estrogens by three sequential oxidations. The isolation of the 19-hydroxy and 19-oxo androgens suggests that the first two oxidations occur at the C19 carbon. However, the mechanism of the third oxidation, which results in C10--C19 bond cleavage, has not been determined. Two proposed mechanisms which remain viable involve either initial 1 beta-hydrogen atom abstraction or addition of the ferric peroxy anion from aromatase to the C19 aldehyde. Semiempirical molecular orbital calculations (AM1) were used to study potential reaction mechanisms initiated by initial 1 beta-hydrogen atom abstraction. Initially, the energetics of carbon--carbon bond cleavage of the keto and enol forms of C1-radicals were studied and were found to be energetically similar. A mechanism was proposed in which the 19-oxo intermediate is subject to initial nucleophilic attack by the protein. The geometry of the A-ring in the androgens is between that for the 1-radicals and estrogen, suggesting that some transition state stabilization for the homolytic cleavage reaction can occur. More recently, studies on liver microsomal cytochrome P450 mediated deformylation of xenobiotic aldehydes supports mechanisms involving an alkyl peroxy intermediate formed by addition of the ferric peroxy anion from aromatase to the C19 aldehyde. Although this intermediate could proceed through several different concerted or non-concerted pathways, one non-concerted pathway involves the heterolytic cleavage of the dioxygen bond resulting in an active oxygenating species (iron-oxene) and a diol. The diol could then undergo hydrogen atom abstraction followed by homolytic carbon--carbon bond cleavage as in the mechanisms modeled previously. When this cleavage was modeled for seven aldehydes, a good correlation with reported experimental aldehyde turnover numbers was obtained. However, when dialkoxy derivatives of the aldehydes are subject to microsomal metabolism, the rates of carbon-carbon cleavage products do not approach the rates of deformylation of the aldehyde analog. PMID- 8476751 TI - Mechanistic studies on aromatase and related C-C bond cleaving P-450 enzymes. AB - Some P-450 systems, notably aromatase and 14 alpha-demethylase catalyse not only the hydroxylate reaction but also the oxidation of an alcohol into a carbonyl compound as well as a C-C bond cleavage process. All these reactions occur at the same active site. A somewhat analogous situation is noted with 17 alpha hydroxylase-17,20-lyase that participates in hydroxylation as well as C-C bond cleavage process. The C-C bond cleavage reactions catalysed by the above enzymes conform to the general equation: [formula: see text] It is argued that all three types of reaction catalyzed by these enzymes may be viewed as variations on a common theme. In P-450 dependent hydroxylation the initially formed FeIII-O-O. species is converted into FeIII-O-OH and the heterolysis of the oxygen-oxygen bond of the latter then gives the oxo-derivative for which a number of canonical structures are possible; for example FeV = O<==>(+.)FeIV = O<==>FeIV-O.. One of these, FeIV-O. behaves like an alkoxyl radical and participates in hydrogen abstraction from C-H bond to produce FeIV-OH and carbon radical. The latter is then quenched by the delivery of hydroxyl radical from FeIV-OH. The latter species may thus be regarded as a carrier of hydroxyl radical. We have proposed that the C-C bond cleavage reaction occurs through the participation of the FeIII O-OH species that is trapped by the electrophilic property of the carbonyl compound giving a peroxide adduct that fragments to produce an acyl-carbon cleavage. Scientific developments leading up to this conclusion are considered. In the first author's views, "The study of mechanisms is not a scientific but a cultural activity. Mechanisms do not aim at an absolute truth but are intended to be a "running" commentary on the status of knowledge in a field. As the structural knowledge in a field advances Mechanisms evolve to take note of the new findings. Just as a constructive "running" commentary provides the stimulus for higher standards of performance, so Mechanisms call for better and firmer structural information from their practitioners". PMID- 8476752 TI - Mechanism of human placental aromatase: a new active site model. AB - Based on Akhtar's ferric peroxide mechanism and on recent studies in our own laboratory, we present a detailed proposal for aromatase action. This picture can account for the known stereochemical consequences at C-19 observed by others using isotopes of hydrogen and oxygen. The postulated process involves anchoring of the 19-hydroxymethyl and 19-oxo groups at the active site by a glutamate residue, which also serves to activate the 19-oxo group for attack by ferric peroxy species in the third oxidative step. PMID- 8476754 TI - A-ring bridged steroids as potent inhibitors of aromatase. AB - The design and syntheses of androstenedione derivatives with bridges spanning the 2,19-, 3,19-, 4,19- and 6, 19-positions are described. 2,19-Bridged compounds bearing hydroxyl groups on the two-carbon bridge (3a and 3b) were designed as stable carbon analogs of potential lactol intermediates in the enzymatic conversion of androgens to estrogens. Compounds 3a and 3b are competitive inhibitors of aromatase. Pyran 25 is a potent, time-dependent inhibitor of aromatase with partial NADPH dependence. These data suggest a mechanism of inhibition for 25 which involves both tight-binding competitive and mechanism based components, with the former predominating. The sulfur, amino, and all carbon analogs of pyran 25 were prepared. Thiopyran 36, piperidine 42 and the all carbon analog 47 are also time-dependent inhibitors of aromatase. Compound 47 is the most potent inhibitor and its time-dependent inhibition is not NADPH dependent. The kinetics of piperidine 42 suggest uncompetitive inhibition. PMID- 8476753 TI - A detailed molecular model for human aromatase. AB - Using a variety of techniques, including sequence alignment, secondary structure prediction, molecular mechanics and molecular dynamics, we have constructed a model for the three-dimensional structure of P-450arom (human aromatase) based on that of P-450cam, the only cytochrome P-450 enzyme for which the crystal structure is known. The predicted structure is found to be in good agreement with current experimental data; both direct, from site-directed mutagenesis studies, and indirect, from the consideration of the structures and activities of known substrates and inhibitors. PMID- 8476755 TI - Structure-activity relationships and binding model of novel aromatase inhibitors. AB - The use of aromatase inhibitors is an established therapy for oestrogen-dependent breast cancer in postmenopausal women. However, the sole commercially available aromatase inhibitor, aminoglutethimide, is not very selective. We have therefore developed fadrozole hydrochloride and CGS 20,267, which are both currently under clinical evaluation. This report will present an analysis of structure-activity relationships in the azole series of inhibitors and give an account of the further optimization of our development compounds, starting from CGS 20,267 over CGP 45,688 and leading to CGP 47,645, the most potent aromatase inhibitor in vivo reported to date. In addition, on the basis of comparisons of these azole-type inhibitors with the most potent steroidal inhibitors published in the literature, we propose a CAMM-generated model describing the relative binding modes of these two classes of compounds at the active site of the enzyme. PMID- 8476756 TI - Regulation of the rat aromatase gene in ovarian granulosa cells and R2C Leydig cells. AB - Aromatase cytochrome P450 is regulated in granulosa cells of ovarian follicles by the synergistic action of FSH and steroids. The effect of FSH can be mimicked by forskolin suggesting that transcription of the aromatase gene is regulated by cAMP. In contrast, aromatase is constitutively expressed in the rat R2C Leydig cells. To characterize the functional regions of the promoter in these two cell types, a fragment containing 534 bp of the aromatase promoter sequence and various deletion mutants were ligated to a reporter gene, chloramphenicol acetyl transferase and used in transient transfection assays. The results suggest that the region between -176 and -31 bp is essential both for cAMP regulation in granulosa cells and constitutive expression in R2C cells. Nuclear proteins from granulosa and R2C cells specifically bind the -176 fragment in an electrophoretic mobility shift assay. Binding was completed by an oligonucleotide (-90/-66 bp) containing a hexameric sequence, AGGTCA, which has been found in the promoters of other steroidogenic genes. These results suggest that cAMP regulation and constitutive expression of the rat aromatase promoter requires sequences between 176 and -31 bp, particularly the sequence AGGTCA at -82/.-77 and nuclear proteins binding to these sequences. PMID- 8476757 TI - Local regulation of primate granulosa cell aromatase activity. AB - Granulosa cells produce inhibin and activin, proteins implicated in the local regulation of preovulatory follicular development. To assess interactions among FSH, LH, inhibin and activin on primate granulosa cell aromatase activity, we studied primary granulosa cell cultures from the ovaries of the common marmoset (Callithrix jacchus), a monkey with an ovarian cycle similar in length to the human cycle. The distinctive action of activin was augmentation of gonadotropin responsive aromatase activity throughout antral follicular development. FSH stimulated aromatase activity in granulosa cells from immature follicles was augmented many fold by picomolar amounts of activin. In cell cultures from preovulatory follicles, the presence of activin stimulated basal aromatase activity in the absence of gonadotropin, as well as augmenting the action of LH. Thus, locally produced activin has the potential to modulate aromatase activity in developing ovarian follicles. By contrast, inhibin or inhibin alpha-subunit purified from bovine follicular fluid had minimal effects on aromatase activity. The only significant effect was slight suppression of FSH-inducible aromatase activity in granulosa cells from immature follicles at an inhibin concentration of 100 ng/ml. The finding that inhibin has a negligible effect on aromatase activity in granulosa cells from mature follicles suggests that it is unlikely to exert a physiologically significant influence on aromatase activity in vivo. However, evidence from other studies suggests that inhibin might affect aromatization indirectly through acting locally to modulate thecal androgen (aromatase substate) production. Therefore, both inhibin and activin have the potential to contribute at different levels to paracrine and autocrine regulation of follicular oestrogen synthesis. PMID- 8476758 TI - Interactions between FSH, estradiol-17 beta and transforming growth factor-beta regulate growth and differentiation in the rat gonad. AB - Estradiol-17 beta (E2) is a mitogen in vivo for the proliferation of granulosa cells in the rat ovary. E2 is synthesized by the preovulatory follicle through a series of gonadotrophin-dependent events: LH stimulates thecal cells to synthesize androgens (androstenedione and testosterone) which are substrates for FSH-induced aromatization to estrogens in granulosa cells. More recently, we have found that transforming growth factor-beta (TGF-beta) stimulates DNA synthesis in rat granulosa cells in vitro and this effect is augmented by FSH. Since E2 is a mitogen in vivo and TGF-beta is the only known growth factor to stimulate proliferation in vitro, the possible link between the actions of E2 and TGF-beta were examined. E2 stimulated the secretion of a TGF-beta-like factor by rat granulosa cells in culture, and with time DNA synthesis was stimulated. The mitogenic action of E2 was enhanced in the presence of FSH, and attenuated by a neutralizing antibody to TGF-beta. The latter observations have identified TGF beta as the "missing-link" in the mitogenic actions of E2 on rat granulosa cells. In addition to the growth-promoting actions of TGF-beta plus FSH, TGF-beta enhanced FSH-induced aromatase activity. Consequently, FSH plus TGF-beta stimulates both the proliferation and aromatization capacity of rat granulosa cells. We propose that interactions between FSH, E2 and TGF-beta lead to the exponential increase in serum E2 levels that occurs during the follicular phase of the cycle. Similarly, FSH stimulates the aromatization of exogenous androgens to estrogen by Sertoli cells isolated from immature rat testes, and there is a correlation between FSH-induced aromatization and mitotic activity. We have shown that FSH plus TGF-beta stimulates DNA synthesis in Sertoli cells. Since E2 increases the secretion of TGF-beta by Sertoli cells, interactions between FSH, E2 and TGF-beta may provide the mitogenic stimulus for Sertoli cells during the prepubertal period. In summary, our findings suggest that the estrogen-induced growth of rat granulosa cells is mediated through the production of TGF-beta, which acts as an autocrine regulator of proliferation. We also propose that the growth-promoting actions of FSH on Sertoli cells may depend upon a cascade series of events involving estrogens and TGF-beta. PMID- 8476759 TI - Regulation of the aromatase activity of human placental cytotrophoblasts by insulin, insulin-like growth factor-I, and -II. AB - Studies to be reviewed were stimulated by the clinical observation, albeit controversial, that diabetic pregnancy may be associated with lower serum oestrogen levels than nondiabetic pregnancy. Pregnant diabetic women are usually intensively treated with insulin to maintain euglycemia, frequently resulting in peripheral hyperinsulinemia. The placenta, which is the primary source of oestrogens during pregnancy, would be exposed to this elevation in circulating insulin levels. Similarly, insulin-like growth factors (IGFs), which are synthesized and secreted by placental tissues and could influence placental function in an autocrine or paracrine fashion, may be elevated in diabetic pregnancy. We will review studies, which show that (i) insulin, insulin-like growth factor-I (IGF-I), and -II inhibit the aromatase activity of human cytotrophoblasts, (ii) these peptides can inhibit aromatase by activation of their respective receptors, and (iii) the potency of IGF-II in suppressing aromatase greatly exceeds that of either insulin or IGF-I. Finally, evidence will be reviewed, which suggests that inositol-glycan mediators ('second messengers') serve as the signal transduction system for insulin's inhibition of aromatase activity. Hence, placental exposure to increased concentrations of insulin and/or IGFs in the pregnant diabetic woman may result in inhibition of aromatase activity and decreased serum oestrogen levels. PMID- 8476760 TI - Estrogen production by fetal rat gonads. AB - Aromatase activity in fetal rat testes and ovaries was demonstrated by the conversion of tritiated testosterone or 19-hydroxyandrostenedione into estrone and estradiol, which were identified and quantified by double isotopic dilution and recrystallization to constant specific activity. Testes formed mostly estradiol, ovaries mostly estrone. Aromatase activity was stimulated by cAMP in both the testes and ovaries as early as 17 days of fetal life. Stimulation by FSH was noted at this same stage in the testis, but not before 3-4 days after birth in the ovary. LH was without effect on aromatase activity in both kinds of gonads. Basal estrogen secretion was non-existent or undetectable in both the testes and ovaries in fetal stages. In the presence of cAMP and as early as 17 days of fetal life, the testes released estradiol, as early as 14 days the ovaries released estrone. Estrogen secretion was stimulated by LH and FSH at fetal stages in the testis and at infantile stages in the ovary. Responsiveness to gonadotrophins closely followed the appearance of the receptors. PMID- 8476761 TI - Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells. AB - Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided. PMID- 8476762 TI - Multiple functions of aromatase and the active site structure; aromatase is the placental estrogen 2-hydroxylase. AB - Androgen aromatase was found to also be estrogen 2-hydroxylase. The substrate specificity among androgens and estrogens and multiplicity of aromatase reactions were further studied. Through purification of human placental microsomal cytochrome P-450 by monoclonal antibody-based immunoaffinity chromatography and gradient elution on hydroxyapatite, aromatase and estradiol 2-hydroxylase activities were co-purified into a single band cytochrome P-450 with approx. 600 fold increase of both specific activities, while other cytochrome P-450 enzyme activities found in the microsomes were completely eliminated. The purified P-450 showed M(r) of 55 kDa, specific heme content of 12.9 +/- 2.6 nmol.mg-1 (+/- SD, n = 4), reconstituted aromatase activity of 111 +/- 19 nmol.min-1.mg-1 and estradiol 2-hydroxylase activity of 5.85 +/- 1.23 nmol.min-1.mg-1. We found no evidence for the existence of catechol estrogen synthetase without concomitant aromatase activity. The identity of the P-450 for the two different hormone synthetases was further confirmed by analysis of the two activities in the stable expression system in Chinese hamster ovarian cells transfected with human placental aromatase cDNA, pH beta-Aro. Kinetic analysis of estradiol 2 hydroxylation by the purified and reconstituted aromatase P-450 in 0.1 M phosphate buffer (pH 7.6) showed Km of 1.58 microM and Vmax of 8.9 nmol.min-1.mg 1. A significant shift of the optimum pH and Vmax, but not the Km, for placental estrogen 2-hydroxylase was observed between microsomal and purified preparations. Testosterone and androstenedione competitively inhibited estradiol 2 hydroxylation, and estrone and estradiol competitively inhibited aromatization of both testosterone and androstenedione. Estrone and estradiol showed Ki of 4.8 and 7.3 microM, respectively, for testosterone aromatization, and 5.0 and 8.1 microM, respectively, for androstenedione aromatization. Androstenedione and testosterone showed Ki of 0.32 and 0.61 microM, respectively, for estradiol 2-hydroxylation. Our studies showed that aromatase P-450 functions as estrogen 2-hydroxylase as well as androgen 19-, 1 beta-, and 2 beta-hydroxylase and aromatase. The results indicate that placental aromatase is responsible for the highly elevated levels of the catechol estrogen and 19-hydroxyandrogen during pregnancy. These results also indicate that the active site structure holds the steroid substrates to face their beta-side of the A-ring to the heme, tilted in such a way as to make the 2 position of estrogens and 19-, 1-, and 2-positions of androgens available for monooxygenation. PMID- 8476763 TI - Aromatase immunoreactivity in the rat brain: gonadectomy-sensitive hypothalamic neurons and an unresponsive "limbic ring" of the lateral septum-bed nucleus amygdala complex. AB - The aromatase (estrogen synthetase) enzyme catalyzes the conversion of androgens to estrogens in peripheral tissues, as well as in the brain. Our study aimed at comparing the brain distribution of aromatase-immunoreactive neurons in male and female, normal and gonadectomized rats. Light microscopic immunostaining was employed using a purified polyclonal antiserum raised against human placental aromatase. Two anatomically separate aromatase-immunoreactive neuronal systems were detected in the rat brain: A "limbic telencephalic" aromatase system was composed by a large population of labeled neurons in the lateral septal area, and by a continuous "ring" of neurons of the laterodorsal division of the bed nucleus of stria terminalis, central amygdaloid nucleus, stria terminalis, and the substantia inominata-ventral pallidum-fundus striati region. The other, "hypothalamic" aromatase system consisted of neurons scattered in a dorsolateral hypothalamic area including the paraventricular, lateral and dorsomedial hypothalamic nuclei, the subincertal nucleus as well as the zona incerta. In addition, a few axon-like processes (unresponsive to gonadectomy) were present in the preoptic-anterior hypothalamic complex, the ventral striatum, and midline thalamic regions. No sexual dimorphism was observed in the distribution or intensity of aromatase-immunostaining. However, 3 days, 2, 3, 8, 16, or 32 weeks after gonadectomy, aromatase-immunoreactive neurons disappeared from the hypothalamus, whereas they were still present in the limbic areas of both sexes. The results indicate the existence of two distinct estrogen-producing neuron systems in the rat brain: (1) a "limbic ring" of aromatase-labeled neurons of the lateral septum-bed nucleus-amygdala complex unresponsive to gonadectomy; and (2) a sex hormone-sensitive "hypothalamic" aromatase neuron system. PMID- 8476764 TI - Aromatase activity in the rat brain: hormonal regulation and sex differences. AB - The intracellular conversion of testosterone to estradiol by the aromatase enzyme complex is an important step in many of the central actions of testosterone. In rats, estrogen given alone, or in combination with dihydrotestosterone, mimics most of the behavioral effects of testosterone, whereas treatment with antiestrogens or aromatase inhibitors block facilitation of copulatory behavior by testosterone. We used a highly sensitive in vitro radiometric assay to analyze the distribution and regulation of brain aromatase activity. Studies using micropunch dissections revealed that the highest levels of aromatase activity are found in an interconnected group of sexually dimorphic nuclei which constitutes a neural circuit important in the control of male sexual behavior. Androgen regulated aromatase activity in many diencephalic nuclei, including the medial preoptic nucleus, but not in the medial and cortical nuclei of the amygdala. Additional genetic evidence for both androgen-dependent and -independent control of brain AA was obtained by studies of androgen-insensitive testicular-feminized rats. These observations suggest that critical differences in enzyme responsiveness are present in different brain areas. Within several nuclei, sex differences in aromatase induction correlated with differences in nuclear androgen receptor concentrations suggesting that neural responsiveness to testosterone is sexually differentiated. Estradiol and dihydrotestosterone acted synergistically to regulate aromatase activity in the preoptic area. In addition, time-course studies showed that estrogen treatment increased the duration of nuclear androgen receptor occupation in the preoptic area of male rats treated with dihydrotestosterone. These results suggest possible ways that estrogens and androgens may interact at the cellular level to regulate neural function and behavior. PMID- 8476765 TI - Aromatase: neuromodulator in the control of behavior. AB - Estrogens are required for both the organization of the brain in early development and adult behavior. Two approaches have been used in our laboratory to study the behavioral role of brain aromatase. First, brain metabolism of testosterone (T) has been related to behavior in the same individual using a well established neuroendocrine model, the ring dove, in which estradiol-17 beta (E2) has specific effects on brain mechanisms of male behavior. Aromatase in preoptic area (POA) (a) has a high activity (Vmax) and strong substrate binding affinity (Km < 5 nM), (b) is regulated by both androgens and estrogens, and the type of regulation differs according to brain area, (c) is influenced by products of an endogenous inactivating pathway, 5 beta-reduction; 5 beta-dihydrotestosterone and other 5 beta-reduced metabolites appear to be non-genomic regulators of the brain aromatase. Preoptic aromatase activity is also influenced by photoperiod and socio-sexual stimuli. The codistribution of regulated aromatase activity and estrogen receptor cells is found to be T-dependent. Our second approach has been to relate the aromatase system to developmental sex differences in brain structure and behavior of the Mongolian gerbil. Neonatal gerbil aromatase is relatively active in the POA, but has a weaker T substrate-binding affinity (Km = 30 nM) than the dove. T acting via its metabolite, E2, masculinizes the sexually dimorphic area of the hypothalamus; the differentiating effect is asymmetric. We suggest that the regulation of the brain aromatase system may be lateralized during steroid-sensitive periods of development. PMID- 8476766 TI - Brain aromatase and the control of male sexual behavior. AB - The activational effects of testosterone (T) on male copulatory behavior are mediated by its aromatization into estradiol. In quail, we have shown by stereotaxic implantation of steroids and metabolism inhibitors and by electrolytic lesions that the action of T and its aromatization take place in the sexually dimorphic medial preoptic nucleus (POM). The distribution and regulation of brain aromatase was studied in this species by product-formation assays measuring aromatase activity (AA) in microdissected brain regions and by immunocytochemistry (ICC). Aromatase-immunoreactive (ARO-ir) neurons were found in four brain regions: the POM, the septal region, the bed nucleus of the stria terminals (BNST) and the tuberal hypothalamus. ARO-ir cells actually outline the POM boundaries. ARO-ir material is found not only in the perikarya of neurons but also in the full extension of their cellular processes including the axons and the presynaptic boutons. This is confirmed at the light level by the demonstration of immunoreactive fibers and punctate structures in brain regions that are sometimes fairly distant from the closest ARO-ir cells. A lot of ARO-ir cells in the POM and BNST do not contain immunoreactive estrogen receptors (ER ir) as demonstrated by double label ICC. These morphological data suggest an unorthodox role for the enzyme or the locally formed estrogens. In parallel with copulatory behavior, the preoptic AA decreases after castration and is restored by T to levels seen in sexually mature males. This probably reflects a change in enzyme concentration rather than a modulation of the activity in a constant number of molecules since the maximum enzymatic velocity (Vmax) only is affected while the affinity (Km) remains unchanged. In addition, T increases the number of ARO-ir neurons in POM and other brain areas suggesting that the concentration of the antigen is actually increased. This probably involves the direct activation of aromatase transcription as demonstrated by RT-PCR studies showing that aromatase mRNA is increased following T treatment of castrates. These activating effects of T seem to result from a synergistic action of androgenic and estrogenic metabolites of the steroid. The anatomical substrate for these regulations remains unclear at present especially in POM where ARO-ir cells do not in general contain ER-ir while androgen receptors appear to be rare based on both [3H] dihydrotestosterone autoradiography and ICC. Transynaptic mechanisms of control may be considered. A modulation of brain aromatase by catecholamines is also suggested by a few pharmacological studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8476767 TI - Molecular and cellular physiology of aromatase in the brain and retina. AB - Due to exceptionally high brain aromatase activity, teleost fish are advantageous for studying neural aromatase regulation, localization, and physiology. To determine the molecular mechanism of enhanced expression, we have isolated, cloned and sequenced a 3 kb full-length aromatase cDNA from a goldfish (Carassius auratus) brain library using a human placental aromatase cDNA as probe. The deduced sequence of goldfish aromatase is 510 amino acids (predicted Mw, 58 kDa) with 69% overall sequence similarity, when compared to human placental aromatase, and higher homologies in presumptive functional domains. A major 3 kb mRNA species was abundant in brain and low or non-detectable in non-neural tissues, reflecting the order of enzyme activities. To determine the cellular basis of high enzyme activity in goldfish brain, a human placental aromatase antibody was used to immunolocalize labeled cells. This antibody immunoprecipitated a single 56 kDa in vitro translation product of goldfish brain poly(A+)RNA and revealed discrete clusters of intensely stained neurons, processes, and terminals concentrated in, but not limited to, reproductive brain centers. Close proximity of aromatase- and androgen receptor-positive neurons in certain regions provides anatomic evidence of a functional relationship between direct and indirect pathways of neural androgen action. Aromatase-positive neurons and fibers formed interconnected networks in novel loci (e.g. retina-->optic tract-->optic tectum), and catalytic activity was confirmed biochemically in these tissues, indicating that neuroestrogen may have a role in visual input and integration. Availability of goldfish-specific nucleotide and antibody probes will facilitate further studies using this model. PMID- 8476768 TI - Aromatase in the human testis. AB - Low levels of testicular estrogen synthesis have been reported in a number of species, but the cellular localization has not been unequivocally established. To study aromatase in the human testis, we have combined immunocytochemistry with direct measurement of enzyme activity in the testicular 6 microns cryosections. Thus, the functionality of the immunoreaction and its sensitivity can be assessed in quantitative terms. Testes were obtained from immediate autopsy from men aged 18-53 years, from surgery from two patients with prostatic cancer (67 and 74 years) and from two normal children aged 8 months and 3 years at autopsy. Benign testicular sex cord tumors were also examined from two unrelated patients aged 5 and 8 years with gynecomastia and diagnosed with Peutz-Jeghers syndrome. Our results consistently showed low to moderate staining intensity of immunoreactive aromatase in comparison to that of normal human placental cryosections. Immunoreactive aromatase was only present in the interstitial Leydig cells and absent from the Sertoli cells of all normal adult testes showing spermatogenesis. Aromatase activity correlated well with the intensity of the immunostain. However, there was no obvious relationship between the level of aromatase activity and increasing age. Generally higher levels were present in testes of young men (18-22 years). No immunostain in any cell type was detected in one 33 year-old patient with testicular cancer. In the testes of the two normal prepubertal boys, no immunostaining was observed. However, intensely stained Sertoli cells as well as high aromatase activity were observed in the testicular tumors of the patients with Peutz-Jeghers syndrome. Our results suggest that Leydig cells are the source of aromatase in normal men but that Sertoli cells may express this enzyme under abnormal conditions. The combined methods for measuring enzyme activity and immunoreactive aromatase are suitable for application to tissues expressing low levels of aromatase. PMID- 8476769 TI - Local aromatase activity in human breast tissues. AB - The presence of oestradiol in malignant breast cells is considered to be an important factor in the promotion of growth of the tumor. Therefore the regulation of the local high intra-tissue oestradiol concentrations, regardless of plasma concentrations, has been investigated. Experimental evidence suggests that in situ biosynthesis of oestrogens is at least partly responsible for the local accumulation of these steroids. In this paper we report further data on measurements in fatty and tumor tissues of local aromatase activities and of concentrations of substrates and products of this enzyme. Data are given on localization of aromatase and on steroid concentrations in tumors and in adipose tissues dissected from different quadrants of breasts with malignant tumors. In adipose tissues small variations in steroid concentrations in fatty tissues were found. No tumor-directed gradients in the adipose tissue-concentrations of the androgens dehydro-epiandrosterone, 5-androstene-3 beta, 17 beta-diol, 4 androstene-3,17-dione and testosterone and of the oestrogens oestradiol, oestrone and their sulfates could be detected. Furthermore no consistent pattern could be recognized in the aromatase activities in the fatty tissues dissected from tumor bearing and non-affected quadrants of the same breast. No correlations between aromatase activity measured in vitro and product concentrations in vivo were found. Therefore the mechanisms for regulation of the local oestradiol levels in breast tissues remain unknown. PMID- 8476770 TI - Prognostic significance of aromatase and estrone sulfatase enzymes in human breast cancer. AB - The aromatase and estrone sulfatase enzymes are important sources of local synthesis of biologically active estrogens in human breast cancer. Significant intratumoral aromatase activity was detected in 91/145 (63%) of tumors and estrone sulfatase was detected in 93/104 (89%) of tumors. There was no relationship between aromatase activity and tumor size, site, nodal status, menopausal status or estrogen receptor status. There was a significant correlation between the aromatase activity and histological grade, with an excess of aromatase-positive in the high grade tumors (P = 0.03). There was a marginally inverse correlation between the aromatase activity and time to relapse (P < 0.1), a significant correlation between aromatase activity and survival after relapse (P < 0.05) but not with overall survival (P > 0.1). Intratumoral estrone sulfatase activity was not significantly correlated to any putative prognostic factors, nor with time to relapse nor overall survival time. PMID- 8476771 TI - Control of aromatase activity in breast cancer cells: the role of cytokines and growth factors. AB - The aromatase complex has a key role in regulating oestrogen formation in normal and malignant breast tissues. Using dexamethasone-treated fibroblasts, derived from breast tumours, breast tumour cytosol and breast tumour-derived conditioned medium (CM) markedly stimulate aromatase activity. The cytokine, interleukin-6 (IL-6) has been identified as a factor present in CM which is capable of stimulating aromatase activity. To examine whether IL-6 may have a role in vivo in regulating breast tissue aromatase activity, IL-6 production and aromatase activity in breast tumour and adipose tissue from breast quadrants were examined. In 5/6 breasts examined so far, aromatase activity was highest in adipose tissue in the breast quadrant containing the tumour or on which the tumour impinged. There was a significant correlation (P < 0.05, Kendall's rank correlation) between IL-6 production and aromatase activity in these breast tissues. It is concluded that IL-6 may have an important role in regulating aromatase activity in breast tissues. PMID- 8476772 TI - Effect of androstenedione on growth of untransfected and aromatase-transfected MCF-7 cells in culture. AB - Aromatase is present in human breast tumors and in breast cancer cell lines suggesting the possibility of in-situ estrogen production via the androstenedione to estrone and estradiol pathway. However, proof of the biologic relevance of aromatase in breast cancer tissue requires the demonstration that this enzyme mediates biologic effects on cell proliferation. Accordingly, we studied the effects of the aromatase substrate, androstenedione, on the rate of proliferation of wild-type and aromatase-transfected MCF-7 breast cancer cells. Androstenedione did not increase cell growth in wild-type MCF-7 cells which contained relatively low aromatase activity and produced 4-fold more estrone than estradiol. In contrast, aromatase-transfected cells contained higher amounts of aromatase, produced predominantly estradiol, and responded to androstenedione with enhanced growth. An aromatase inhibitor fadrozole hydrochloride, blocked the proliferative effects of androstenedione providing evidence for the role of aromatase in this process. As further evidence of the requirement for aromatase, cells transfected with the neomycin resistance expression plasmid but lacking the aromatase cDNA did not respond to androstenedione. These studies provide evidence that aromatase may have a biologic role for in-situ synthesis of estrogens in breast cancer tissue. PMID- 8476773 TI - Biological characterization of A-ring steroids. AB - Hydroxylated 2,19-methylene-bridged androstenediones were designed as potential mimics of enzyme oxidized intermediates of androstenedione. These compounds exhibited competitive inhibition with low micromolar affinities for aromatase. These inhibitory constants (Ki values) were 10 times greater than the 2,19 methylene-bridged androstenedione constant (Ki = 35-70 nM). However, expansion of the 2,19-carbon bridge to ethylene increased aromatase affinity by 10-fold (Ki = 2 nM). Substitution of a methylene group with oxygen and sulfur in this expanded bridge resulted in Ki values of 7 and 20 nM, respectively. When the substituent was an NH group, the apparent inhibitory kinetics changed from competitive to uncompetitive. All of these analogs exhibited time-dependent inhibition of aromatase activity following preincubation of the inhibitor with human placental microsomes prior to measuring residual enzyme activity. Part of this inhibition was NADPH cofactor-dependent for the 2,19-methyleneoxy- but not for the 2,19 ethylene-bridged androstenedione. The time-dependent inhibition for these four analogs was very rapid since they exhibited tau 50 values, the t1/2 for enzyme inhibition at infinite inhibitor concentration, of 1 to 3 min. These A-ring bridged androstenedione analogs represent a novel series of potent steroidal aromatase inhibitors. The restrained A-ring bridge containing CH2, O, S, or NH could effectively coordinate with the heme of the P450 aromatase to allow the tight-binding affinities reflected by their nanomolar Ki values. PMID- 8476774 TI - Anti-tumor and endocrine effects of non-steroidal aromatase inhibitors on estrogen-dependent rat mammary tumors. AB - The non-steroidal aromatase inhibitor CGS 20,267, at maximally effective doses in non-tumor bearing adult female rats, elicits endocrine effects mimicking those seen after surgical ovariectomy and thus induces a "medical" ovariectomy. We now report on studies characterizing the anti-tumor and endocrine effects of three orally active non-steroidal aromatase inhibitors, CGS 20,267, CGP 45,688 and CGP 47,645, in adult female rats bearing estrogen-dependent DMBA-induced mammary tumors. Doses ranging from 3 to 3000 micrograms/kg were given by gavage once daily for 6 weeks. After 6 weeks of treatment, the ED50 for suppression of tumor volume was 10-30, 100 and 3-10 micrograms/kg for CGS 20,267, CGP 45,688 and CGP 47,645, respectively. The maximally effective dose for anti-tumor efficacy was 300, 1000 and 100 micrograms/kg for each of the three inhibitors, respectively. The observed potent anti-tumor efficacy was accompanied by potent endocrine effects. Thus, disruption of ovarian cyclicity (at maximal doses rats remained in constant diestrus) was observed in all animals from the 2nd or 3rd week of treatment to the end of the 6-week treatment period. Uterine weight, at the maximally effective doses for each of the three inhibitors, was suppressed to between 42 and 28% of pre-treatment levels. This suppression was similar to the suppression of uterine weight (27% of pre-treatment) seen after ovariectomy. Serum estradiol concentrations in rats treated with 300 micrograms/kg CGS 20,267 were significantly suppressed to 12% of pre-treatment levels and serum luteinizing hormone (LH) concentrations were elevated 3 to 4-fold over pre treatment levels. Thus the potent anti-tumor efficacy seen with each of the three non-steroidal aromatase inhibitors was accompanied in each case by a variety of endocrine effects corresponding to those seen after ovariectomy. PMID- 8476775 TI - Distribution of aromatase activity in cultured neurons and glia cells. AB - Aromatase plays a crucial role in the mechanism of action of testosterone in the central nervous system. Nevertheless, the exact cellular localization of this enzymatic complex within the different cell populations of the brain is still uncertain. In the experiments described here the presence of aromatase (assayed by the tritiated water method) has been evaluated in the two main cellular components of the brain: neurons and glia. Neurons, mixed glial cells, type 1 astrocytes, were obtained in cultures; oligodendrocytes were prepared by gradient ultracentrifugation. The results indicate that, among the different cells tested, only neurons possess a significant degree of aromatase activity, while the enzymatic activity is extremely low in mixed glial cell and in astrocyte preparations. Oligodendrocytes seem to be completely inactive in this respect. PMID- 8476776 TI - Action of endogenous steroid inhibitors of brain aromatase relative to fadrozole. AB - To study mechanisms of aromatase inhibition in brain cells, a highly effective non-steroidal aromatase inhibitor (Fadrozole; 4-[5,6,7,8-tetra-hydroimidazo- (1,5 a)-pyridin-5-yl] benzonitrile HCl; CGS 16949A) was compared with endogenous C-19 steroids, known to be formed in the preoptic area, which inhibit oestrogen formation. Using a sensitive in vitro tritiated water assay for aromatase activity in avian (dove) preoptic tissue, the order of potency, with testosterone as substrate was: Fadrozole (Ki < 1 x 10(-9) M) > 4-androstenedione > 5 alpha androstanedione > 5 alpha-dihydrotestosterone (Ki = 6 x 10(-8) M) > 5 beta androstanedione > 5 beta-dihydrotestosterone (Ki = 3.5 x 10(-7) M) > 5 alpha androstane-3 alpha,17 beta-diol (Ki = 5 x 10(-6) M) > 5 beta-androstane-3 beta,17 beta-diol. Five other steroids, 5 beta-androstane-3 alpha,17 beta-diol, 5 alpha androstane-3 beta,17 beta-diol, progesterone, oestradiol and oestrone, showed no inhibition at 10(-4) M. The kinetics indicate that endogenous C-19 steroids show similar competitive inhibition of the aromatase as Fadrozole. Mouse (BALB/c) preoptic aromatase was also inhibited by Fadrozole. We conclude that endogenous C 19 metabolites of testosterone are effective inhibitors of the brain aromatase, and suggest that they bind competitively at the same active site as Fadrozole. PMID- 8476777 TI - Competitive product inhibition of aromatase by natural estrogens. AB - In order to better understand the function of aromatase, we carried out kinetic analyses to assess the ability of natural estrogens, estrone (E1), estradiol (E2), 16 alpha-OHE1, and estriol (E3), to inhibit aromatization. Human placental microsomes (50 micrograms protein) were incubated for 5 min at 37 degrees C with [1 beta-3H]testosterone (1.24 x 10(3) dpm 3H/ng, 35-150 nM) or [1 beta-3H,4 14C]androstenedione (3.05 x 10(3) dpm 3H/ng, 3H/14C = 19.3, 7-65 nM) as substrate in the presence of NADPH, with and without natural estrogens as putative inhibitors. Aromatase activity was assessed by tritium released to water from the 1 beta-position of the substrates. Natural estrogens showed competitive product inhibition against androgen aromatization. The Ki of E1, E2, 16 alpha-OHE1, and E3 for testosterone aromatization was 1.5, 2.2, 95, and 162 microM, respectively, where the Km of aromatase was 61.8 +/- 2.0 nM (n = 5) for testosterone. The Ki of E1, E2, 16 alpha-OHE1, and E3 for androstenedione aromatization was 10.6, 5.5, 252, and 1182 microM, respectively, where the Km of aromatase was 35.4 +/- 4.1 nM (n = 4) for androstenedione. These results show that estrogen inhibit the process of androgen aromatization and indicate that natural estrogens regulate their own synthesis by the product inhibition mechanism in vivo. Since natural estrogen binds to the active site of human placental aromatase P-450 complex as competitive inhibitors, natural estrogens might be further metabolized by aromatase. This suggests that human placental estrogen 2-hydroxylase activity is catalyzed by the active site of aromatase cytochrome P-450 and also agrees with the fact that the level of catecholestrogens in maternal plasma increases during pregnancy. The relative affinities and concentration of androgens and estrogens would control estrogen and catecholestrogen biosynthesis by aromatase. PMID- 8476778 TI - Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women. AB - Aromatase activity, as well as steroid receptors, exists in nonfunctional ovarian tumors. Steroid receptor status has been reported to be related to prognosis in ovarian cancer patients. We determined aromatase activity and progesterone receptor (PR) and estrogen receptor (ER) levels in 43 ovarian tumors obtained from postmenopausal women. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%). Eighty-three percent (10/12) of mucinous cystadenoma tissues showed positive PR with high aromatase activity, while 93% (13/14) of malignant tumors showed negative PR and low aromatase activity. Aromatase activity was detected in 95% (20/21) of PR-positive tumors, being greater than in PR-negative tumors (P < 0.002). There was a positive correlation between aromatase activity and PR (rs = 0.49, P < 0.001). However, there was no correlation between aromatase activity and ER. In 17 patients (43%), the serum estradiol level was higher than 30 pg/ml and there was a positive correlation among estradiol, estrone, androstenedione and testosterone. However, serum steroid levels were not correlated with aromatase activity, PR or ER. Aminoglutethimide inhibited aromatase activity of benign and malignant ovarian tumors, uterine myoma, choriocarcinoma cells and purified human placental P 450arom in a similar manner. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful prognostic factor in ovarian cancers. PMID- 8476779 TI - Aromatase activity and the effect of estradiol and testosterone on DNA synthesis in endometrial carcinoma cell lines. AB - Human endometrial and breast carcinoma cell lines were examined for aromatase activity and the effects of sex steroids (estradiol and testosterone) on DNA synthesis. Aromatase activity was high (greater than 500 fmol/10(7) cells/24 h) in the cell lines MCF-7 and OMC-2, moderate (100-499 fmol/10(7) cells/24 h) in the cell lines HEC-59 and Ishikawa, and low (less than 100 fmol/10(7) cells/24 h) in the HHUA cell line. A substantial stimulation of DNA synthesis by estradiol (10(-9)M) was observed in cell lines HEC-59, OMC-2, and MCF-7, with an increase in [3H]thymidine uptake of over 250%. The Ishikawa cell line was stimulated moderately (115-249%). No estradiol-induced increase in DNA synthesis was observed in HHUA. Responsiveness of DNA synthesis to testosterone was observed in cell lines that showed the greatest response to estradiol, namely HEC-59, OMC-2, and MCF-7. Otherwise, estrogen-responsiveness did not always correlated with a significant aromatase activity. These data suggest that some but not all endometrial carcinomas may possess an aromatase-dependent growth stimulating system. PMID- 8476780 TI - Growth suppression of MCF-7 human breast cancer cells by aromatase inhibitors: a new system for aromatase inhibitor screening. AB - In our previous study we found that MCF-7 cells possess aromatase activity and stimulate estrogen receptor-mediated growth. The pathways through which androgens are converted to estrogens by aromatase and estrogens interact with estrogen receptors contribute significantly to growth stimulation. The administration of aromatase inhibitor results in suppression of growth stimulation by androgens. This system enabled us to assess directly the biological activities of aromatase inhibitors. Aromatase activity was inhibited in a dose-dependent manner by the addition of aminoglutethimide and CGS 16949A, competitive inhibitors, and of 14 alpha-hydroxy-4-androstene-3,6,17-trione and 4-hydroxy-androstenedione, mechanism based inhibitors. After preincubation with mechanism-based inhibitors, aromatase activity was significantly suppressed, whereas after preincubation with competitive inhibitors, it was adversely increased. These effects were concentration- and time-dependent. Preincubation with competitive inhibitors resulted in augmentation of subsequent androgen stimulation of thymidine incorporation, while preincubation with mechanism-based inhibitors resulted in diminished stimulation by subsequent androgen administration. These results suggest that in MCF-7 cells competitive inhibitors adversely induce aromatase and accelerate the subsequent androgen stimulation of DNA synthesis. Suicide inhibitors are more effective than competitive inhibitors. This system will be useful for aromatase inhibitor screening. PMID- 8476781 TI - MCF-7 human breast carcinomas in nude mice as a model for evaluating aromatase inhibitors. AB - While hormone-dependent, mammary tumors induced with carcinogens (DMBA or NMU) in intact rats have been used extensively for studying aromatase inhibitors, there is currently no suitable model to investigate their effects in human breast cancers in vivo. While hormone responsive tumors can be formed in the athymic mouse using human breast carcinoma MCF-7 cells, due to the low ovarian estrogen production, tumor growth is induced with estradiol supplementation. Thus, this model is unsuitable for studies of aromatase inhibitors. We have induced tumors without the need for estrogen supplementation by co-inoculating MCF-7 cells with Matrigel, a basement membrane preparation, into intact athymic mice. In one experiment, 45 days after inoculation, mice were assigned to the control group or 4-hydroxyandrostenedione (4-OHA) (1 mg/day s.c.) treatment for 52 days. Tumor volumes in the control mice increased 672%, whereas tumor volumes in the treated mice did not change significantly (178.9 +/- 16.2 to 336.6 +/- 120 mm3). In the second experiment, 55 days after inoculation, groups of mice were treated with the antiestrogen, tamoxifen (5 micrograms/day s.c.) or vehicle (controls). Tumor volumes in the control mice increased 325% in 58 days, whereas there was no significant change in tumor volume in the tamoxifen treated group (338.8 +/- 55.3 to 330.6 +/- 84.9 mm3). The results suggest that (1) the tumors resulting from MCF-7 cells co-inoculated with Matrigel are estrogen-dependent and (2) tamoxifen and 4-OHA were effective in suppressing growth of these tumors. The results suggest that this model should be useful for evaluating the effects of aromatase inhibitors and for comparing breast cancer treatments. PMID- 8476782 TI - Substituted 1-[benzofuran-2-yl)-phenylmethyl]-imidazoles as potent inhibitors of aromatase in vitro and in female rats in vivo. AB - Substituted 1-[(benzofuran-2-yl)-phenylmethyl]-imidazoles are a new class of potent aromatase inhibitor with in vitro IC50 values < 10 nM for certain members using human placental enzyme. At a dose of 2 mg/kg in PMSG-stimulated rats, selected compounds effectively reduce the oestradiol levels by 82-98%. PMID- 8476783 TI - Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats. AB - The antitumor effect of exemestane (FCE 24304), an irreversible aromatase inhibitor, given alone or in combination with tamoxifen, was investigated in rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. The compounds were given once daily, 6 days a week for 4 weeks. Exemestane, given at the dose of 20 mg/kg/day s.c., induced 26% complete (CR) and 18% partial (PR) tumor regressions, compared to 0% CR and 6% PR observed in controls. Tamoxifen, given at 1 mg/kg/day p.o., induced 16% CR and 13% PR. The combined treatment caused 41% CR and 16% PR, thus resulting in a higher antitumor effect than either single treatment. The appearance of new tumors was reduced by each single treatment and almost totally prevented by the combined treatment. Serum prolactin (PRL) levels, assayed 4 h after the last dose, were unchanged in the group treated with the combination, whereas tamoxifen alone caused a slight increase of serum PRL. These results indicate that estrogen deprivation through aromatase inhibition and estrogen receptor antagonism causes a better inhibition of DMBA-induced mammary tumors than either treatment modality alone. PMID- 8476784 TI - Org 33201: a new highly selective orally active aromatase inhibitor. AB - Org 33201 has been selected as a very potent aromatase inhibitor. The compound is an enantiomer of a SC2H5 substituted imidazoylethylphenalene. Org 33201 inhibited human aromatase activity for 50% at a concentration of 2.2 x 10(9) mol/l. More than 200-fold higher concentrations were needed for the inhibition of other cytochrome P-450 enzymes. In vivo the compound was active in rats (ED50 = 0.035 mg/kg) and dogs (1 mg/kg gave 70% inhibition) after oral administration. It can be concluded that Org 33201 is a potent and highly selective orally active aromatase inhibitor. PMID- 8476785 TI - The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. AB - The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Recent developments with imidazole compounds that inhibit aromatase activity suggest their clinical use as potent inhibitors of estrogen biosynthesis in postmenopausal breast cancer patients. In this Phase I, open-label, dose-range finding study, we examined the inhibitory potency of CGS 20267 on blood and urine levels of estradiol, estrone and estrone sulfate in 8 patients with metastatic breast cancer. Studies included evaluation of adrenal and thyroid function to look for evidence of general hydroxylase inhibition at dose levels effective for aromatase blockade. Patients were administered CGS 20267 at doses of 0.1 and 0.25 mg, once a day in ascending doses over a 12-week period. Preliminary data reveal that CGS 20267 elicits a striking suppression in plasma estradiol, estrone and estrone sulphate which was observed in some patients as quickly as within 24 h of the first dose. Estrogen suppression of over 90% was achieved within 2 weeks of therapy. No alterations in either baseline or ACTH (cortrosyn) stimulated cortisol and aldosterone levels were observed through the 12 weeks of therapy. In addition, 24 h urine sodium and potassium values were not appreciably altered during therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer and effectively reduces blood and urine estrogens to undetectable levels. PMID- 8476786 TI - Aminoglutethimide (AG) and hydrocortisone (HC) in bone metastases: a retrospective study. AB - The response rate in bone metastases in 57 patients treated with aminoglutethimide and hydrocortisone was retrospectively assessed. All the X-rays were reviewed by two senior radiologists. A response was observed in 23% of the patients, a stabilization in 32%. The survival was not different whether a response or stabilization was observed. Conversely, survival was significantly worse in patients who experienced a progressive disease. PMID- 8476787 TI - Festschrift in honor of the 60th birthday of Dr. Allan S. Hoffman: Part 1. PMID- 8476788 TI - Allan S. Hoffman--overview and appreciation. PMID- 8476789 TI - Introduction of amine groups on poly(ethylene) by plasma immobilization of a preadsorbed layer of decylamine hydrochloride. AB - In order to introduce amine groups on poly(ethylene) (PE) surface, PE surfaces were preadsorbed with decylamine hydrochloride (DA.HCl) and subsequently treated with an argon plasma. It was shown by XPS (X-ray Photoelectron Spectroscopy), that approximately half of the preadsorbed (mono)layer was immobilized and that a substantial part (60-70%) of the incorporated nitrogen containing groups were amine groups. The availability of the surface amine groups for reactions was investigated by applying a gas phase reaction with 4-trifluoromethylbenzaldehyde and by a reductive methylation reaction in aqueous solution with 14C formaldehyde. A maximal number of reactive amine groups was found after a plasma treatment time of 2 s. The reductive methylation reaction was used to estimate the surface concentration of amine groups resulting in a typical surface concentration of 1 x 10(-6) mol/m2 after a plasma treatment time of 2 s. PMID- 8476790 TI - Surface properties of RGD-peptide grafted polyurethane block copolymers: variable take-off angle and cold-stage ESCA studies. AB - Variable take-off angle and cold-stage ESCA measurements were utilized to analyze the surface composition of five polyurethane block copolymers. The polymers studied included a PTMO-polyurethane control, a carboxylated version of the control polyurethane, and three different peptide grafted (GRGESY, GRGDSY, and GRGDVY) polyurethanes. On dry samples the nitrogen signal detected using ESCA decreased with increasing take-off angle (i.e. as the specimen was probed closer to the surface) for all five polymers. This was believed to be due to the depletion of nitrogen-containing urethane hard segments at the surface. For all five polymers, the surface nitrogen concentration, associated with the hard segment, increased upon hydration. A greater increase of nitrogen concentration was observed for the peptide grafted polymers which suggests that grafting of the hydrophilic peptides to the polyurethane augments the hard segment enrichment at the surface upon hydration. Upon dehydration, the nitrogen concentration decreased for all five polymers suggesting migration of the more hydrophobic PTMO soft segment to the surface. In vitro endothelial cell adhesion showed an increase of cell attachment on prehydrated RGD-containing peptide grafted polyurethanes, but not on the other polymers. This result suggests an enhancement of peptide density at the aqueous interface, in good agreement with the ESCA studies. PMID- 8476791 TI - Mechanism of cytoplasmic calcium changes in platelets in contact with polystyrene and poly(acrylamide-co-methacrylic acid) surfaces. AB - Changes in cytoplasmic free calcium levels ([Ca2+]i) in platelets in contact with polystyrene (PSt) and poly(acrylamide-co-methacrylic acid) (PAAmMAc) particles were evaluated and results were compared with those from two representative biological calcium agonists; thrombin and calcium ionophore A23187. PSt particles stimulated a steep increase in cytoplasmic calcium levels in platelets as much as thrombin and A23187. Serratia protease-treated platelets showed a steep increase in [Ca2+]i by PSt particles, suggesting that PSt surfaces can initiate platelet activation independent of a glycoprotein Ib (GPIb)-mediated pathway. By contrast, dibucaine-treated platelets showed little increase in [Ca2+]i by PSt particles, indicating that microfilament assembly, including binding of GPIb with actin binding protein, should be required for platelet activation in contact with PSt surfaces. PAAmMAc particles induced little increase in cytoplasmic calcium levels in platelets. However, PAAmMAc particle-treated platelets demonstrated little response to thrombin in terms of an increase in [Ca2+]i and ATP release, suggesting the possibility that PAAmMAc surfaces may regulate [Ca2+]i by influencing platelet metabolism. Furthermore, sodium azide-treated platelets showed an increase in [Ca2+]i in platelets when contacting PAAmMAc particles, supporting the suggestion that PAAmMAc surfaces could regulate platelet functions. Fluorescence polarization measurements using 1,6-diphenyl-1,3,5 hexatriene-loaded platelets revealed that PAAmMAc particles increased membrane fluidity in platelets, which may be due to physicochemical interaction with PAAmMAc surfaces. PMID- 8476792 TI - Surface modification of polymeric biomaterials with poly(ethylene oxide), albumin, and heparin for reduced thrombogenicity. AB - Appropriate surface modification has significantly improved the blood compatibility of polymeric biomaterials. This article reviews methods of surface modification with water-soluble polymers, such as polyethylene oxide (PEO), albumin, and heparin. PEO is a synthetic, neutral, water-soluble polymer, while albumin and heparin are a natural globular protein and an anionic polysaccharide, respectively. When grafted onto the surface, all three macromolecules share a common feature to reduce thrombogenicity of biomaterials. The reduced thrombogenicity is due to the unique hydrodynamic properties of the grafted macromolecules. In aqueous medium, surface-bound water-soluble polymers are expected to be highly flexible and extend into the bulk solution. Biomaterials grafted with either PEO, albumin, or heparin are able to resist plasma protein adsorption and platelet adhesion predominantly by a steric repulsion mechanism. PMID- 8476793 TI - Cell-attachment activities of surface immobilized oligopeptides RGD, RGDS, RGDV, RGDT, and YIGSR toward five cell lines. AB - Tetrapeptides, Arg-Gly-Asp-Ser (RGDS), Arg-Gly-Asp-Val (RGDV), and Arg-Gly-Asp Thr (RGDT), respectively, appearing in the cell-attachment domains of fibronectin, vitronectin, and collagen, and pentapeptide Tyr-Ile-Gly-Ser-Arg (YIGSR) appearing in B1 chain of laminin, were synthesized by liquid-phase procedure. Bioactivities of RGD, RGDX (X = S, V and T), YIGSR, and YIGSR-NH2 as cell recognition determinants were investigated by cell-attachment test using these oligopeptides immobilized to ethylene-acrylic acid copolymer (PEA) film. The cell lines used were A431, NRK, CHO-K1, HeLa.S3, and RLC-16 cells. It was found that the residue X in RGDX plays an important role for cell-attachment activity of RGDX, and, regarding YIGSR, introduction of NH2 residue at the C terminal of the pentapeptide enhances the cell-attachment activity. PMID- 8476794 TI - Physico-chemical surface characterization of hyaluronic acid derivatives as a new class of biomaterials. AB - Three hyaluronic acid derivatives with different types and/or percentages of esterification, were analyzed by means of static contact angle measurements, SEM, ESCA, ATR/FT-IR, WAXS, DSC and TGA. The physico-chemical characterization of the three different samples, in both dry and wet state, was provided in terms of surface and bulk properties. ESCA and infrared analyses showed that the surface composition of all samples differs from that of the bulk. The hydrophilic hydrophobic character of the samples changed according to the chemical composition as shown by ESCA and contact angle measurements. Both infrared and contact angle measurements reveal that surface restructuring occurred upon hydration for all the samples and the greater the hydrophilic character of the sample, the greater and faster the restructuring phenomenon. A clear picture of the different types of chemical groups has been established at different depth for the three materials. PMID- 8476795 TI - Release behavior of bioactive agents from pH-sensitive hydrogels. AB - Controlled release systems of theophylline, proxyphylline and oxprenolol.HCl exhibiting modulated drug delivery were prepared by using pH-sensitive anionic copolymers of 2-hydroxyethyl methacrylate with acrylic acid or methacrylic acid. Drug release studies were carried out in simulated biological fluids. The initial drug release rates and the drug release mechanisms were dependent upon the pH and ionic strength of the buffer solution as well as its salt composition. Initial drug diffusion coefficients in these swelling-controlled release systems were calculated from the release curves; they were of the order of 10(-7) cm2/s and were dependent upon the degree of swelling. The drug release mechanism was non Fickian in all the dissolution media studied. Lowest release rates were observed for drug release from nonionized polymer networks in agreement with the relationship between ionization, swelling and drug release. PMID- 8476796 TI - Identification of proteins absorbed to hemodialyser membranes from heparinized plasma. AB - The protein layers formed during contact of plasma with hemodialysis membranes were studied. Dialysers having membranes of cellulose acetate (CA), saponified cellulose ester (SCE), cuprophane (CUP), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN) were used. Heparinized human plasma was recirculated through the dialysers for four hours. They were then rinsed and the proteins adsorbed to the membranes were eluted with 2% SDS. The yields of protein from the different membranes increased in the order: PMMA < CA < SCE < CUP < PAN. This is the probable order of increasing hydrophilicity. SDS-PAGE and Western blots were performed on the dialyser eluates. The blots were positive for most of the twenty proteins tested for. There were some interesting differences in adsorption patterns among the different membrane materials, notably for high molecular weight kininogen (HMWK), plasminogen and the C3 component of complement. HMWK was intact in the eluates from CA, CUP and SCE, whereas on PMMA and PAN there was evidence of cleavage, suggesting that activation of the contact phase of coagulation was more extensive on the latter two materials. Intact plasminogen was visible on all the blots. However, low molecular weight fragments were visible in the PAN eluates, suggesting activation of the fibrinolytic pathway. Low molecular weight fibrinogen fragments eluted from PAN membranes support this conclusion. C3 was visible in the blots obtained for all membrane materials, and the data suggest that complement is activated by all the membranes. A C3 fragment at about 30 kD (possibly C3d) was seen in the blots for the cellulosic membranes but not for PMMA or PAN. PMID- 8476797 TI - Properties controlling the diffusion and release of water-soluble solutes from poly(ethylene oxide) hydrogels. 1. Polymer composition. AB - This study examines the state of water-association with poly(ethylene oxide), as evidenced by diffusivity, in a series of crosslinked polyurethanes made from poly(ethylene glycols) of a range of molecular weights. As a subsidiary underpinning exercise the correlation of diffusivity with water content at relatively high levels of swelling (> 45%) using a variety of semi-empirical equations was analyzed. Three water-soluble compounds with similar molecular weights and which exhibit minimal interaction with the polymer, as shown by their partition coefficients, were chosen for this part of the research programme. These were proxyphylline, morphine hydrochloride and caffeine. The best statistical correlations of the data were obtained for plots of: (a) diffusivity against weight percent water; and (b) log diffusivity against the reciprocal of the weight percent of water in the hydrogels. Proxyphylline results for the high levels of swelling compositions were augmented with data from lower swelling compositions and a clear break in the slope of diffusivity against percentage of water in the swollen hydrogel was obtained. This indicated a change in the nature of the diffusion at this point. The probability of this transition point corresponding to a change for diffusion through water bound as trihydrate to diffusion in free water is discussed. PMID- 8476798 TI - The no-fault panacea? PMID- 8476799 TI - Pre-eclampsia and cytokine induced oxidative stress. PMID- 8476800 TI - Classifying perinatal death: experience from a regional survey. AB - OBJECTIVE: To examine problems encountered in classifying perinatal death using the systems proposed by Hey et al. (1986) and Cole et al. (1986). SUBJECTS: 451 deaths from a regional perinatal mortality survey of which 293 had a post mortem examination. METHODS: Documents from each death were reviewed by four assessors, one from each discipline, selected randomly from a pool of obstetricians, paediatricians, general practitioners and midwives. Each assessor classified the cause of death blind to the others. The degree of agreement between assessors was calculated for the full and shortened obstetric and fetal-neonatal classifications using the kappa statistic for inter-rater agreement. RESULTS: The kappa statistic, which is a measure of the proportion of agreement above chance, gave a value of 0.55 for the full obstetric classification and 0.58 for the full fetal and neonatal classification when all four assessors made an assignment. An assignment was omitted in 6.2%, but the kappa value of zero for these omissions suggested that this was a nonsystematic result due to random protocol violations. The grouped (shortened) classifications generated a higher kappa value of 0.62 for the nine point obstetric system and 0.67 for the six point fetal and neonatal (New Wigglesworth) system. Post mortem had little effect on agreement. The best agreement levels observed were for congenital anomaly. CONCLUSION: This survey highlighted the complexity of the 22 and 24 point classifications, the uneven distribution of deaths within their categories, and the variable levels of agreement between professionals classifying deaths, thus questioning the validity of individual maternity units of health districts generating local data in this degree of detail for comparative purposes in regional and national statistics. Grouping the original categories led to greater agreement particularly for the New Wigglesworth classification. The role of post mortems in clarifying the cause of fetal and neonatal death needs further investigation. PMID- 8476801 TI - Pregnancy after renal transplantation: 25 years experience in Spain. AB - OBJECTIVE: To study the outcome of pregnancy in renal transplant patients in Spain. DESIGN: A retrospective review based on two consecutive national inquiries. SETTING: Departments of Obstetrics and Gynaecology and Renal Transplant Units in Spain. SUBJECTS: Pregnant women who had renal transplants between 1965 and 1989. MAIN OUTCOME MEASURES: From the preliminary inquiry the frequencies of miscarriage, therapeutic abortion, preterm birth, fetal malformation, twins, stillbirths, neonatal deaths and loss of maternal renal function were recorded. The subsequent, more detailed inquiry provided additional information including donor type, previous rejection episodes and interval between rejection and pregnancy, previous creatinine level, previous hypertension and development of hypertension in pregnancy, developments during labour and delivery and the occurrence of intra uterine growth retardation and low birth weight. RESULTS: The preliminary inquiry yielded information about 133 pregnancies. The miscarriage rate was 10% and the therapeutic abortion rate was 16%. Of the 99 pregnancies that continued, 46% ended before term and 53% progressed to term. The perinatal mortality rate was 107.8 per 1000 and 4% of the infants had minor congenital malformations. The second inquiry yielded more detailed data about 66 pregnancies. There were no therapeutic abortions and 12% of the pregnancies ended in miscarriage. Among the 58 pregnancies that reached > or = 28 weeks gestation, preterm birth occurred in 28 (48%) and intra uterine growth retardation occurred in 17 (29%). Among 48 women with normal renal function before pregnancy, the perinatal mortality rate was 68 per 1000, the miscarriage rate was 8% and in 10 of these women (21%) renal function was impaired after pregnancy. In contrast, among 18 women with impaired renal function before pregnancy, the perinatal mortality rate was 142 per 1000, the miscarriage rate was 22% and in six of these women (33%) renal function deteriorated after the pregnancy. Impairment of renal function was most common in women with hypertension during pregnancy or with rejection episodes during the year before conception. CONCLUSIONS: Women with a renal transplant can have a successful pregnancy, but there are definite risks for both mother and fetus. Pregnancy should be discussed with the woman and encouraged only if there is good renal graft function. PMID- 8476802 TI - A randomised trial of 45 minutes and 15 minutes incremental oxytocin infusion regimes for the induction of labour in women of high parity. AB - OBJECTIVE: To investigate whether in women of high parity induction of labour using a regimen of intravenous oxytocin, increasing incrementally at 45 min intervals, is safer than one increasing at 15 min intervals. SETTING: University of Benin Teaching Hospital, Department of Obstetrics and Gynaecology, Benin City, Nigeria. DESIGN: Randomised controlled trial. SUBJECTS: Ninety women of parity 5 or more requiring induction of labour by infusion of oxytocin were randomly allocated to incremental increases at either 45 min intervals (experimental group) or 15 min intervals (control group). MAIN OUTCOME MEASURES: Mode of delivery; complications of labour and delivery (uterine rupture, precipitate labour, hyperstimulation, postpartum haemorrhage, perineal tears, puerperal pyrexia); number of days spent in hospital. RESULTS: The 45 min incremental regimen resulted in longer induction-delivery intervals (estimate of difference in population medians 2 h, 95% confidence interval (CI) 1-4 h); less precipitate labour (odds ratio (OR) 0.09, 95% CI 0.03-0.30); less uterine hyperstimulation (OR 0.23, 95% CI 0.09-0.59); and a reduced length of hospital stay (estimate of difference in population medians 3 days, 95% CI 2-5 days). With the 45 min interval regimen there was a reduction in the occurrence of uterine rupture, postpartum haemorrhage, perineal tears and puerperal pyrexia, but these differences did not reach statistical significance. CONCLUSION: For the induction of labour in women of high parity the infusion rate of oxytocin should be increased every 45 min rather than every 15 min until contractions occur three times in 10 min and this infusion rate of oxytocin is maintained until delivery. PMID- 8476803 TI - Randomised comparison of routine versus highly selective use of Doppler ultrasound in low risk pregnancies. AB - OBJECTIVE: To help answer the question: should Doppler ultrasound of the umbilical circulation be made available to all pregnant women as part of their routine antenatal care? DESIGN: A randomised trial. SETTING: St James's University Hospital, Leeds. SUBJECTS: 2025 low risk primigravid women. MAIN OUTCOME MEASURES: Obstetric intervention rates and short term neonatal morbidity. RESULTS: The incidence of abnormal Doppler was low (1.7%) with complete absence of end diastolic flow in only 0.3% of cases. No significant differences could be demonstrated between control and study women in any of the outcomes measured. CONCLUSION: This study did not demonstrate any benefit or harm from Doppler ultrasound as a routine screening test for all low risk women, whereas our previous studies have suggested that it is useful in high risk pregnancies. Any marginal returns on extending access to Doppler ultrasound from high risk to all women must be small. Since this test has excellent performance characteristics (sensitivity and specificity) for the prediction of fetal hypoxia and acidosis our results call into question the cost to benefit ratio of all tests designed to predict these outcomes in low risk women. PMID- 8476804 TI - Intra-observer and inter-observer reliability of the pulsatility index calculated from pulsed Doppler flow velocity waveforms in three fetal vessels. AB - OBJECTIVE: Study of the intra observer and inter observer reliability of the pulsatility index, calculated from pulsed Doppler recordings of three fetal vessels. DESIGN: Flow velocity waveforms (FVW) were recorded from the umbilical artery, the fetal descending aorta and the fetal internal carotid artery. Intra observer reliability was assessed in six fetuses; ten repeated measurements were performed by one observer. Inter-observer reliability was studied in 14 fetuses; two observers performed two repeated measurements in each fetus. SETTING: A tertiary referral hospital. SUBJECTS: High risk pregnancies with a gestational age ranging from 29 to 42 weeks. MAIN OUTCOME MEASURES: Analysis of variance with repeated measurements and a graphical method were used for data analysis. Intra observer repeatability was expressed as Intraclass Correlation Coefficient (IntraCC). Inter-observer agreement was expressed as Interclass Correlation Coefficient (InterCC). RESULTS: IntraCC for umbilical artery, descending aorta and internal carotid artery were 0.91, 0.78, and 0.54, respectively. InterCC values for these vessels were 0.39, 0.45 and 0.34, respectively. No systematic differences between the two observers except for the fetal descending aorta, were apparent. IntraCC decreased remarkable when fetuses with absent end diastolic velocities were excluded from the analysis. CONCLUSION: The pulsatility index (PI) used for fetal measurements has a poor reliability. This is of serious concern when clinical use of FVW measurements is considered as a diagnostic tool. PMID- 8476805 TI - Fetal cerebral Doppler in the recognition of fetal compromise. AB - OBJECTIVE: To establish reference ranges for the human fetal middle cerebral artery pulsatility index (MCA PI) for the local obstetric population, and to compare computerised antenatal fetal heart rate (FHR) analysis with the MCA PI as indicators of fetal compromise. DESIGN: Prospective data collection for selected patients. SETTING: High risk pregnancy unit of a teaching hospital. SUBJECTS: Group 1 consisted of 18 healthy women with uncomplicated singleton pregnancies. Group 2 consisted of 27 women admitted to the high risk pregnancy unit over a 9 month period with intrauterine growth retardation and other related problems; all these women were delivered by prelabour caesarean section. INTERVENTION: Serial Duplex sonography to determine fetal MCA PI in Groups 1 and 2. Serial FHR analysis using computerised numerical techniques in Group 2 only. MAIN OUTCOME MEASURES: Serial MCA PI values from 24 to 39 completed weeks of gestation in Group 1. Comparison of serial MCA PI values with FHR analysis in relation to fetal outcome in Group 2. RESULTS: In Group 1 the MCA PI diminished significantly as gestation advanced from 1.73 (SD 0.25) at 24 weeks to 1.38 (SD 0.26) at 39 weeks (P < 0.01). In Group 2 eleven babies were hypoxaemic at delivery: all had low MCA PI values while only nine had an abnormal FHR prior to delivery. CONCLUSION: In normal pregnancy, there is a fall in the fetal MCA PI with advancing gestation which probably reflects a decreasing vascular resistance to fetal cerebral blood flow. Hypoxaemia at delivery appeared to be better recognised by the fetal MCA flow velocity waveform than the FHR analysis. This increased sensitivity, however, was achieved at the expense of a reduced specificity. Larger studies are needed to confirm the findings of this preliminary investigation. PMID- 8476806 TI - Abnormal cervical cytology following large loop excision of the transformation zone: a case controlled study. AB - OBJECTIVES: To determine factors that may predict cytological outcome at 6 months following large loop excision of transformation zone (LLETZ) for cervical intra epithelial neoplasia (CIN) and to investigate the outcome in women with continuing cytological abnormality. DESIGN: Case controlled retrospective study. SETTING: Dudley Road Hospital, Birmingham and Midland Hospital for Women. SUBJECTS: Fifty-eight women with abnormal follow up cytology and a control group of 116 women. MAIN OUTCOME MEASURES: The relation between pretreatment and treatment factors and cytological outcome, and the relation between cytology and histology in women who had biopsies for persistent abnormal cytology. RESULTS: Univariate and stepwise logistic regression analysis showed that the number of sectors of atypical transformation zone (lesion size) and the excision margin status of the large loop excision specimen are of prognostic importance for the prediction of cytological abnormality at the 6 month follow up visit. Sixteen women have undergone further cervical biopsy. Of the five cases of persistent CIN, four had cytological changes showing moderate or severe dyskaryosis. Of the 11 women with koilocytosis or normal histology, 10 had mild dyskaryosis or borderline changes on their follow up cytology. CONCLUSION: Lesion size and excision margin status are important correlates of follow up cytology when treating patients for CIN with LLETZ. All women with abnormal cervical cytology at follow up should undergo colposcopic assessment. Excision biopsy is indicated if follow up cytology shows moderate or severe dyskaryosis, especially if still present 12 months after treatment. PMID- 8476807 TI - Is HIV infection associated with an increase in the prevalence of cervical neoplasia? AB - OBJECTIVE: To test the hypotheses: (1) that HIV infection predisposes to cervical intraepithelial neoplasia (CIN); (2) that this CIN is a result of HIV related immunosuppression; and (3) that this CIN is a result of immunosuppression causing increased expression of the potentially oncogenic viruses, human papilloma virus (HPV), Epstein Barr virus (EBV) and herpes simplex virus (HSV). DESIGN: A matched cross sectional study. SETTING: The Department of Gynaecological Oncology, The Samaritan Hospital, London; the Department of Genitourinary Medicine, St Mary's Hospital, London; and the Family Planning Clinic, Claremont Terrace, Glasgow. SUBJECTS: Fifty HIV seropositive women enrolled from the Genitourinary Medicine Department and the Drug Dependency Unit at St Mary's Hospital, London, and the Unit of Infectious Diseases at Ruchill Hospital, Glasgow. Forty-three HIV seronegative controls enrolled from the Department of Genitourinary Medicine at St Mary's Hospital, matched against 43 of the seropositive women for age, age at first intercourse, lifetime number of sexual partners, and smoking habit. MAIN OUTCOME MEASURES: Associations between CIN, as detected by cytology and histology, and HIV infection. Association was also sought between CIN and immunosuppression, as measured clinically by T4 cell number, beta-2-microglobulin and p24 antigen. Associations of these with: (1) HPV, as detected by Southern blot testing and the polymerase chain reaction; (2) EBV, as detected by Southern blot testing; and (3) HSV, as detected by tissue culture of endocervical swabs, was also studied. RESULTS: There was no significant difference in the prevalence of CIN or oncogenic viruses between HIV seropositive and seronegative women in the absence of immunosuppression. If the HIV infected women showed signs of immunosuppression, the prevalence of CIN was increased. No association was shown between detection of HPV, EBV and HSV and immunosuppression or CIN. CONCLUSION: HIV infection may only be associated with an increased risk of CIN when immunosuppression is present. PMID- 8476808 TI - Type III collagen content in the skin of postmenopausal women receiving oestradiol and testosterone implants. AB - OBJECTIVE: To investigate the effect of subcutaneous oestradiol and testosterone on the proportion of type III collagen in the skin of postmenopausal women. DESIGN: A cross sectional comparison. SETTING: Dulwich Hospital menopause clinic. SUBJECTS: Fourteen untreated women and 11 women who had received subcutaneous oestradiol and testosterone for a median 8.0 years (range 3-14). Ten of the untreated women received subcutaneous hormone implants and the effect on skin collagen was studied prospectively. MEASUREMENTS: The proportion of type III collagen in skin biopsies taken from the lateral aspect of the thigh. RESULTS: The median type III collagen content in the skin of the women who had received hormone replacement therapy (25.4%, range 21.4-30.2) was significantly higher (P < 0.01) than in the untreated women (19.6%, range 18.2-28.8). The proportion of type III collagen in the skin of 10 untreated women increased significantly (P < 0.01) from a median of 19.9% (range 18.2-23.9) to 22.4% (range 20.5-31.5) following 6 months of treatment with hormone implants. CONCLUSION: This study indicates an increase in the proportion of type III collagen in women receiving hormone replacement therapy. PMID- 8476809 TI - Laparoscopic ovarian diathermy: an effective treatment for anti-oestrogen resistant anovulatory infertility in women with the polycystic ovary syndrome. AB - OBJECTIVE: To determine the long term efficacy of laparoscopic ovarian diathermy in the management of refractory anovulatory infertility in women with the polycystic ovary syndrome. DESIGN: Open study of 50 women treated over a period of 3 years and 3 months, with follow up until 18 months after the last woman was treated. SETTING: Teaching Hospital. SUBJECTS: Fifty consecutive women with refractory anovulatory infertility (mean duration 5.3 (SD 3.5) years). All had been treated unsuccessfully with anti-oestrogens and more than half with gonadotrophins. INTERVENTIONS: Laparoscopic ovarian diathermy. MAIN OUTCOME MEASURES: Ovulatory cycles and pregnancies. RESULTS: Forty-three women (86%) ovulated following ovarian diathermy; the mean time to ovulation was 23 (SD 6.2) days. Three nonresponders ovulated following anti-oestrogen treatment to which they were previously resistant. Thirty-three women have conceived 58 pregnancies; 22 had no treatment other than ovarian diathermy prior to their first post operative conception; in seven an anti-oestrogen was given because of lengthening cycles; two were treated elsewhere with gonadotrophins without prior postdiathermy anti-oestrogen therapy and conceived; four had the operation repeated and two of these conceived. Twenty-six women conceived within the first 8 post-operative months. Forty-two pregnancies ended in the birth of normal live healthy babies, eight are ongoing and eight miscarried. Of the 22 women who had no pelvic abnormality other than polycystic ovaries, 19 (86%) have had one or more successful pregnancies. CONCLUSION: Laparoscopic ovarian diathermy is a very effective treatment for anti-oestrogen resistant anovulatory infertility in women with the polycystic ovary syndrome and should be considered as the next step in those who fail to respond to anti-oestrogen treatment. PMID- 8476810 TI - Adverse effects on sperm movement characteristics in women with minimal and mild endometriosis. AB - OBJECTIVE: To test the effect of peritoneal fluid from infertile women with minimal or mild endometriosis on sperm movement characteristics in comparison with fertile and infertile women with no endometriosis. DESIGN: A prospective observer-blind trial. SETTING: Academic infertility department. SUBJECTS: 57 women undergoing diagnostic laparoscopy or laparoscopic sterilisation. MAIN OUTCOME MEASURES: Changes in sperm movement characteristics in semen samples provided during routine infertility investigation or from sperm donors. Computer assisted semen analysis (CASA) performed using a Celltrack-S system. RESULTS: Significant reductions in linearity (P < 0.05), amplitude of lateral head displacement (P < 0.01), straight line velocity (P < 0.01), and curvilinear velocity (P < 0.01) (but not percentage motility) were observed. CONCLUSIONS: Peritoneal fluid from women with minimal or mild endometriosis adversely effects sperm movement characteristics in comparison to fertile women. PMID- 8476811 TI - Pressor, heart rate and plasma catecholamine responses to noradrenaline in pregnant and nonpregnant women. AB - OBJECTIVE: To study cardiovascular responses to noradrenaline during early pregnancy. DESIGN: Administration of incremental intravenous infusions of noradrenaline under basal conditions. SETTING: University Hospital, Nottingham. SUBJECTS: Nineteen women admitted for termination of pregnancy in first or second trimester and 18 nonpregnant women as control subjects. INTERVENTIONS: Recordings of blood pressure and heart rate responses during the infusion of noradrenaline. Blood samples taken before, during and after the infusion. MAIN OUTCOME MEASURES: Evoked responses of systolic and diastolic blood pressure and heart rate at steady state during the noradrenaline infusion. Plasma catecholamine concentrations measured by high performance liquid chromatography. RESULTS: There were no significant differences between the evoked pressor responses to noradrenaline in pregnancy compared to the nonpregnant state, but there was a lesser bradycardia in response to a standardised change in blood pressure. Neither basal plasma catecholamine concentrations nor those achieved during infusion of noradrenaline differed between pregnant and nonpregnant women. Thirty minutes after discontinuance of the infusion there was a persistent elevation of heart rate in all women, although plasma catecholamine concentrations had returned to basal levels. In pregnant women, systolic and diastolic blood pressures were also elevated at this time, compared to preinfusion levels. CONCLUSION: Cardiovascular regulatory mechanisms are altered in pregnancy with a diminution in the bradycardic response to a pressor challenge evoked by noradrenaline and a delayed recovery from that challenge. PMID- 8476812 TI - Cardiovascular autonomic reflexes in mid-pregnancy. AB - OBJECTIVE: To study the physiological responses to noninvasive cardiovascular autonomic function tests in normal pregnancy. DESIGN: Cardiovascular autonomic responses in 60 women at 22 to 29 weeks gestation and 62 nonpregnant women were investigated using the Valsalva manoeuvre as well as orthostatic, quiet breathing, deep breathing, and isometric handgrip tests. RESULTS: Compared with nonpregnant women, those who were pregnant showed significantly lower heart rate variability during normal breathing and a blunted tachycardic reaction to blowing during the Valsalva manoeuvre. The vagally controlled biphasic heart rate response to standing was also attenuated in the pregnant group. CONCLUSIONS: The cardiovascular responses were blunted in mid-pregnancy indicating a decrease in parasympathetic cardiovascular control. PMID- 8476813 TI - Supernumerary fallopian tubes. PMID- 8476814 TI - Spontaneous rupture of the uterine artery in pregnancy. PMID- 8476815 TI - Reversal of fetal benzodiazepine intoxication using flumazenil. PMID- 8476816 TI - Sensitivity of pocket Doppler fetal heart detectors in early pregnancy: a comparative study. PMID- 8476817 TI - Short term psychological outcome of surgical intervention for endometriosis. PMID- 8476818 TI - The House of Commons Health Committee Report on the Maternity Services. A personal view. PMID- 8476819 TI - Sweeping of the membranes is an effective method of induction of labour in prolonged pregnancy: a report of a randomised trial. PMID- 8476820 TI - Platelets in pregnancy induced hypertension. PMID- 8476821 TI - Do we need randomised trials of antenatal tests of fetal wellbeing? PMID- 8476822 TI - Platelets and pregnancy. PMID- 8476823 TI - A national survey to assess current use of computerised information systems in obstetrics. AB - OBJECTIVE: To ascertain the number and type of obstetric computer systems (OCS) in Great Britain, and to ascertain user satisfaction with these systems. DESIGN: A postal questionnaire was circulated to every consultant obstetrician in Great Britain at the beginning of 1992. MAIN OUTCOME MEASURES: Information was sought on the hardware, software and uses of obstetric computer systems. Satisfaction with, benefits and problems of the system were also assessed. RESULTS: There was an 87.5% response rate. Of the 264 units questioned, 100 units reported that they had a computer system. Sixty-five units used terminals connected to a mainframe or minicomputer and 17 used stand-alone personal computers (PCs). Local area networks (LANs) were used in 19 units and wide area network (WANs) in 22 units. Software varied from commercial turnkey systems to in-house systems. The quoted annual running cost ranged from 50 pounds to 48,000 pounds. Most units were satisfied with their system. Problems included slow operating times, unreliability, user unfriendliness, deficiencies in training and inadequate customer support services. CONCLUSIONS: Obstetric computer systems are now coming into widespread use. Despite problems, the use of such systems is likely to increase. This survey establishes a database for those units who are considering acquiring or changing their computer system for the purpose of audit or research. PMID- 8476824 TI - Memory loss during pregnancy. AB - OBJECTIVE: To investigate possible impairment of memory during pregnancy. DESIGN: The performance of pregnant women in a variety of tests of memory was compared to that of controls. SETTING: The Bristol Maternity Hospital. SUBJECTS: Forty-eight volunteer pregnant women attending for routine antenatal checks were compared to 19 nonpregnant controls. MAIN OUTCOME MEASURES: Subjectively perceived rating of memory impairment, objective measures of recall, recognition and priming memory. RESULTS: Pregnant and control groups were given a series of tests of memory at the end of which they were asked to rate their own memory at present compared to some weeks ago (when they were not pregnant). Of the pregnant women 39 out of 48 (81%) rated their current memory as being impaired; only three out of 19 (16%) of the control subjects did so. Objective tests revealed that the pregnant group was significantly impaired in the recall of lists of words, particularly when learning was incidental rather than explicit. The pregnant group was also significantly impaired in two measures of priming memory. No significant deficit was found in recognition. The deficits were found for both primigravid and multigravid women, and were present in all trimesters of pregnancy. CONCLUSIONS: The majority of women believe their memory to be impaired during pregnancy. Objectively, during pregnancy there is significant impairment of memory as tested by recall or by priming, but not by recognition. The pattern of memory loss differs from that of other amnesic conditions. Information imparted to pregnant patients may not be retained as well as might be expected. PMID- 8476825 TI - Retrospective analysis of platelet numbers and volumes in normal pregnancy and in pre-eclampsia. AB - OBJECTIVE: To determine the distribution of platelet volumes and numbers through pregnancy, and to compare these to changes in platelet volumes and numbers in women with pre-eclampsia. SUBJECTS: Four hundred twenty-eight women with normal pregnancy from whom four or more platelet measurements were available were identified. 74 women with pre-eclampsia (blood pressure > or = 140/90 mmHg, at least 0.5 g protein/24 h urine collection) from whom platelet measurements were available between 27 and 30 weeks of gestation were identified. RESULTS: Mean platelet volume and platelet number remained constant in normal pregnancies between the first trimester and the end of pregnancy. A persistent increase of > or = 0.8 fl (> or = 90th centile) in mean platelet volume was found in 14 out of 15 pre-eclamptic patients between 24 weeks and 38 weeks of gestation and in only 13 of 428 normal pregnant individuals. Platelet numbers were decreased by > or = 50 x 10(9)/l (i.e. to less than the 10th centile) in 12 of the 15 patients with pre-eclampsia. 10% of the normal pregnant population showed a similar decline in platelet numbers showing that changes in platelet numbers may be a less accurate assessment of the development of pre-eclampsia. CONCLUSION: We suggest that longitudinal determination of platelet volumes may be of use in identifying those women at risk of pre-eclampsia. PMID- 8476826 TI - Hypnosis: practical applications and theoretical considerations in normal labour. AB - OBJECTIVE: To assess the effects of hypnotherapy on the first and second stages of labour in a large group of pregnant women. DESIGN: A semi-prospective case control study in which women attending antenatal clinics were invited to undergo hypnotherapy. SUBJECTS: One hundred twenty-six primigravid women with 300 age matched controls, and 136 parous women having their second baby with 300 age matched controls. Only women who had spontaneous deliveries were included. SETTING: Aberdare District Maternity Unit, Mid Glamorgan, Wales. INTERVENTION: Six sessions of hypnotherapy given by a trained medical hypnotherapist during pregnancy. OUTCOME MEASURES: Analgesic requirements, duration of first and second stages of labour. RESULTS: The mean lengths of the first stage of labour in the primigravid women was 6.4 h after hypnosis and 9.3 h in the control group (P < 0.0001); the mean lengths of the second stage were 37 min and 50 min, respectively (P < 0.001). In the parous women the corresponding values were 5.3 h and 6.2 h (P < 0.01); and 24 and 22 min (ns). The use of analgesic agents was significantly reduced (P < 0.001) in both hypnotised groups compared with their controls. CONCLUSION: In addition to demonstrating the benefits of hypnotherapy, the study gives some insight into the relative proportions of mechanical and psychological components involved in the longer duration of labour in primigravid women. PMID- 8476827 TI - Prediction of fetal acidaemia in pregnancies complicated by maternal diabetes mellitus by biophysical profile scoring and fetal heart rate monitoring. AB - OBJECTIVE: To determine whether computer assisted fetal heart rate analysis or the biophysical profile score can provide noninvasive prediction of fetal acidaemia. DESIGN: Cross sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital School of Medicine, London. SUBJECTS: Forty-one women with pregnancies complicated by diabetes mellitus. INTERVENTIONS: Fetal heart rate (FHR) monitoring with computer assisted analysis, biophysical profile score (BPS) and cordocentesis for measurement of umbilical venous blood glucose concentration and blood gases, up to 24 h before delivery at 27 to 39 weeks gestation. RESULTS: The mean umbilical venous blood pH was significantly lower than the normal mean for gestation, and was below the 5th centile in 18 pregnancies, including all six cases where the mother had nephropathy and hypertension. The mean pO2 was not significantly different from the normal mean for gestation. There were significant associations between fetal acidaemia and both the BPS (r = 0.46, P < 0.01) and FHR variation (r = 0.42, P < 0.01). However, of the 12 acidaemic fetuses of non-nephropathic mothers, nine had normal BPS and six had normal FHR variation. CONCLUSIONS: In pregnancies complicated by maternal diabetes mellitus, BPS and FHR variation are of limited value in the prediction of fetal blood pH. PMID- 8476828 TI - Chirality in the umbilical cord. AB - OBJECT: To determine the chiral varieties of the vascular helix of the umbilical cord and find their normal proportions. DESIGN: Differences between the sexes were tested by a chi 2 test and the hypothesis that left-handed types occur in 50% of cases was tested using the binomial distribution. SETTING: United Arab Emirates. SUBJECT: Gulf Arab singletons from consecutive normal births, 100 male and 100 female. RESULTS: Left-handed helices predominate at 76.5%; right-handed contribute 15.5%; mixed forms, where both chiralities co-exist, were found in 6.5%; indeterminable chirality due to poor helix formation, or varices, reached 1.5%. A significant sex difference could not be established. Chiral generation, on genetic and mechanical-rotational hypotheses, is discussed. CONCLUSION: The chirality of the cord is easily determined and is the sole distinguishing feature of the cord. Chirality should be entered in the birth record and in pathological descriptions for whatever value it may have in relation to fetal, or postnatal, characteristics and morbidity. PMID- 8476829 TI - Randomised controlled trial comparing endometrial resection with abdominal hysterectomy for the surgical treatment of menorrhagia. AB - OBJECTIVE: To evaluate the effectiveness of endometrial resection as a surgical treatment for menorrhagia. DESIGN: Randomised controlled trial. SETTING: Gynaecology department at a teaching hospital. SUBJECTS: Two hundred women needing surgical treatment for menorrhagia between January 1990 and May 1991. After withdrawal of four women 97 underwent hysterectomy and 99 underwent endometrial resection. MAIN OUTCOME MEASURES: Patient satisfaction 4 months after surgery; post-operative complications; length of hospital stay; duration of time before return to work, normal daily activities and sexual intercourse; change in premenstrual symptoms. RESULTS: The difference in patient satisfaction between endometrial resection (84 out of 99) and abdominal hysterectomy (89 out of 95) just reached statistical significance in favour of abdominal hysterectomy at 4 months after surgery (difference = 9%, 95% confidence intervals (CI) 1.1%-17.5%). Post-operative morbidity, length of hospital stay and time taken to return to work, normal daily activities and sexual intercourse were significantly less in the endometrial resection group. However, the premenstrual symptoms of dysmenorrhoea, bloating and breast tenderness were less frequent after hysterectomy. CONCLUSION: In the short term, endometrial resection was almost as satisfactory as abdominal hysterectomy for the surgical treatment of menorrhagia, and was associated with less morbidity. However, even at 4 months after surgery, there was a failure rate of at least 10% in those in whom endometrial resection appeared complete. Longer term comparative studies are necessary before the widespread introduction of endometrial resection as an alternative to abdominal hysterectomy for the surgical treatment of menorrhagia. PMID- 8476830 TI - An economic evaluation of transcervical endometrial resection versus abdominal hysterectomy for the treatment of menorrhagia. AB - OBJECTIVE: To evaluate the relative health service cost of endometrial resection versus abdominal hysterectomy for the treatment of menorrhagia and the value women attach to their health state before and after surgery. DESIGN: A prospective economic evaluation running alongside a randomised controlled trial. SETTING: The gynaecology department of a teaching hospital. SUBJECTS: 200 women requiring surgical treatment of menorrhagia between January 1990 and May 1991; after withdrawals, 97 women underwent hysterectomy and 99 underwent endometrial resection. MAIN OUTCOME MEASURES: The total health service cost of managing women in the two arms of the trial until 4 months after their operation. The change in women's valuation of their health state a fortnight after and a minimum of 4 months after surgery relative to that 1 month prior to their operation. RESULTS: Total health service costs are significantly higher amongst abdominal hysterectomy patients (mean 1059.73 pounds) than amongst endometrial resection patients with a mean difference of 499.68 pounds (95% CI 432 pounds-567 pounds). This significant difference exists under alternative assumptions about the difference in lengths of stay in hospital between the two treatment groups and the hotel cost per in-patient day. On a scale of 0 to 100, relative to a month before surgery, there is a statistically significant difference in favour of endometrial resection between the two groups in the increase in value women attach to their health state at a fortnight after surgery (mean difference 11.2; 95% CI 0.6-21.7), but not at a minimum of 4 months after surgery (mean difference 7; 95% CI -17.4 to 3.4). CONCLUSIONS: On the basis of health service resource cost up to 4 months after surgery, endometrial resection has a cost advantage over abdominal hysterectomy. However, given the fact that a subgroup of women requires retreatment due to resection failure and that this study considers a relatively short period of follow up, the long term costs and benefits of endometrial resection need to be evaluated before widespread diffusion is justified. PMID- 8476831 TI - Flow cytometric studies of ploidy and proliferative indices in the Yorkshire trial of adjuvant progestogen treatment of endometrial cancer. AB - OBJECTIVE: To estimate whether flow cytometric indices provide independent measures of prognosis or predict response to prophylactic progestogens in endometrial cancer. DESIGN: Endometrial tumour specimens were retrieved and analysed by flow cytometry from 257 women who had been randomly allocated in a previous trial to receive prophylactic progestogen in addition to conventional therapy for endometrial carcinoma. SETTING: Fourteen district and two teaching hospitals in West Yorkshire. SUBJECTS: Women developing primary endometrial cancer between 1975 and 1983. MAIN OUTCOME MEASURES: Tumour ploidy status and proliferative indices and the relation of these to tumour stage and grade, to prognosis and to response to progestogens. RESULTS: Ploidy status and proliferative indices were related to tumour stage, grade and patient survival but were not independent predictors of survival. They did not predict patients who would respond to progestogens although there was a nonsignificant trend towards patients with diploid tumours surviving longer after progestogen treatment. CONCLUSIONS: Flow cytometry adds little to established prognostic indicators for endometrial cancer. PMID- 8476832 TI - Early discharge following vaginal hysterectomy. AB - OBJECTIVE: To assess the feasibility of discharging selected patients home within 72 h of vaginal hysterectomy. DESIGN: Women for whom vaginal hysterectomy was planned and who were invited to take part. Those who accepted were visited at home by a staff nurse experienced in gynaecology to assess home conditions and family support. If these were suitable, the general practitioner was informed and invited to comment. If the operation was uneventful women were discharged on the third post operative day and visited at home by the nurse until the seventh day. SETTING: Leeds Western Health Authority. MAIN OUTCOME MEASURES: The number of minor complications requiring treatment by the general practitioner, the readmission rate and the acceptability to the woman and her family. RESULTS: For 11 out of 61, home conditions proved unsuitable for early discharge. In six of the remaining 50, abdominal hysterectomy proved preferable to vaginal. Thirty women were discharged home on the third day after vaginal hysterectomy, five on the fourth and seven on the fifth. Two developed urinary tract infections, treated by their general practitioners. Two required readmission to hospital. Twenty-eight of 30 discharged on the third post operative day and nine of 12 discharged on the fourth or fifth post operative day were enthusiastic about the scheme. CONCLUSIONS: Early discharge following uncomplicated vaginal hysterectomy in selected patients appears to be a safe procedure, appreciated by the majority of women. Its adoption as a routine procedure would enable the surgical throughput in a unit to be maintained on a smaller bed complement. PMID- 8476833 TI - Does elective cryopreservation of all embryos from women at risk of ovarian hyperstimulation syndrome reduce the incidence of the condition? AB - OBJECTIVES: To analyse the incidence and factors associated with the ovarian hyperstimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk. DESIGN: Two hundred forty-one consecutive IVF/GIFT cycles from January to December 1989. SETTING: Specialist fertility unit, Manchester, UK. INTERVENTIONS: Pituitary suppression was effected by a daily subcutaneous injection of buserelin (500 micrograms) beginning 7 days before the expected menses. The ovarian stimulation was with variable amounts of human menopausal gonadotrophin. Ovulation was induced with 10,000 i.u. human chorionic gonadotrophin (hCG). From January to May (period A), gametes/embryos were replaced and 2000 i.u. hCG given, irrespective of the serum oestradiol (E2) concentration. From June to December (period B), all the embryos from women with an E2 > 3500 pg/ml on the day of ovulatory trigger were electively cryopreserved. MAIN OUTCOME MEASURES: Serum E2, features of moderate or severe OHS, clinical pregnancies. RESULTS: The OHS occurred in 10/105 (9.5%) and 12/136 (8.8%) cycles in periods A and B, respectively. Fewer women (6% versus 60%, P < 0.05) who had their embryos cryopreserved developed severe OHS compared with women with an E2 > 3500 pg/ml who became pregnant after gamete/embryo transfer in period A. The main factors associated with the development of OHS were serum E2 concentrations > 3500 pg/ml, whether gamete/embryos were replaced and the additional hCG given, the occurrence of a pregnancy and the presence of polycystic ovary disease. CONCLUSION: The elective cryopreservation of all embryos from women with high E2 levels reduced the severity, but not the incidence of symptomatic OHS. PMID- 8476834 TI - Findings on lipid peroxidation and antioxidant function in hypertensive complications of pregnancy. AB - OBJECTIVE: To assess lipid peroxidation and antioxidant function in hypertensive complications of pregnancy. DESIGN: Cross sectional study comparing pre-eclamptic and control patients. SETTING: Tampere University Hospital, Finland. SUBJECTS: Twenty healthy women with normal, uncomplicated pregnancy; 23 women with severe pre-eclampsia; 20 women with mild pre-eclampsia; and 13 women with pregnancy induced hypertension. MAIN OUTCOME MEASURES: Conjugated dienes; thiobarbituric acid--reactive material or malondialdehyde (MDA); fluorescent chromolipids (FCL); glutathione peroxidase (GSHPx); selenium; uric acid; and vitamin E. RESULTS: Lipid peroxidation assessed by the appearance of conjugated dienes and malondialdehyde was significantly increased in the hypertensive patients as compared with control patients. Lipid peroxidation products also showed high correlation to the level of blood pressure, but failed to show significant relation to the outcome of the fetus. The activities of erythrocyte and plasma glutathione peroxidase were increased in severe pre-eclampsia, and high levels of plasma or platelet glutathione peroxidase were found to have some association with fetal growth retardation or asphyxia. CONCLUSIONS: Our findings give support to those few studies considering lipid peroxidation as an important factor in the pathogenesis of pre-eclampsia. The rise in antioxidants is probably of compensatory nature responding to the increased peroxide load in pre-eclampsia and may reflect the severity of the disease. PMID- 8476835 TI - Fetal pleural effusion following maternal indomethacin therapy. PMID- 8476836 TI - Post partum haemorrhage secondary to Marfan's disease of the uterine vasculature. PMID- 8476837 TI - Indomethacin use to control gross polyhydramnios complicating triplet pregnancy. PMID- 8476838 TI - Percutaneous nephrostomies in women with cervical cancer. PMID- 8476839 TI - Combined laparoscopic and micro-laparotomy removal of benign cystic teratomata. PMID- 8476841 TI - Is obstetric and neonatal outcome worse in fetuses who fail to reach their own growth potential? PMID- 8476840 TI - Simplifying laparoscopic surgery for ectopic pregnancies. PMID- 8476842 TI - Genital tract infections associated with the intrauterine contraceptive device can be reduced by inserting the threads into the uterine cavity. PMID- 8476843 TI - Genital tract infections associated with the intrauterine contraceptive device can be reduced by inserting the threads into the uterine cavity. PMID- 8476844 TI - The cytological detection of persistent cervical intraepithelial neoplasia after local ablative treatment: a comparison of sampling devices. PMID- 8476845 TI - Solution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex: intercalation of the covalently attached benzo[a]pyrenyl ring into the helix and displacement of the modified deoxyguanosine. AB - This paper reports on the solution structure of the (+)-cis-anti-[BP]dG adduct positioned opposite dC in a DNA oligomer duplex which provides the first experimentally based solution structure of an intercalative complex of a polycyclic aromatic hydrocarbon covalently bound to the N2 of deoxyguanosine. The combined NMR-energy minimization computation studies were undertaken on the (+) cis-anti-[BP]dG adduct embedded in the same d(C5-[BP]G6-C7).d(G16-C17-G18) trinucleotide segment of the complementary 11-mer duplex studied previously with the stereoisomeric trans adducts. The exchangeable and nonexchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D2O solution. The solution structure of the (+)-cis-anti-[BP]dG-dC 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by upper and lower bounds deduced from NOESY data sets as restraints in energy minimization computations. The benzo[a]pyrene ring of [BP]dG6 is intercalated between intact Watson-Crick dC5.dG18 and dC7.dG16 base pairs in a right-handed DNA helix. The benzylic ring is in the minor groove while the pyrenyl ring sacks with flanking dC5 and dC7 bases on the same strand. The deoxyguanosine ring of [BP]dG6 is not Watson-Crick base paired but displaced into the minor groove with its plane parallel to the helix axis and stacks over the sugar ring of dC5. The dC17 base on the partner strand is displaced from the center of the helix toward the major groove by the intercalated benzo[a]pyrene ring. This intercalative structure of the (+)-cis-anti-[BP]dG-dC 11-mer duplex exhibits several unusually shifted proton resonances which can be readily accounted for by the ring current contributions of the deoxyguanosine and pyrenyl rings of the [BP]dG6 adduct. Several phosphorus resonances are shifted to low and high field of the unperturbed phosphorus spectral region and have been assigned to internucleotide phosphates centered about the [BP]dG6 modification site. These studies define the changes in the helix at the central trinucleotide segment needed to generate the intercalation site for the covalently bound (+)-cis-anti-[BP]dG adduct.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8476846 TI - Site-directed alterations to the geometry of the aspartate transcarbamoylase zinc domain: selective alteration to regulation by heterotropic ligands, isoelectric point, and stability in urea. AB - Structural aspects requisite for allosteric function in the regulatory chain of aspartate transcarbamoylase were explored by site-specific amino acid insertion or substitution within the zinc domain in the region of contact between the catalytic and regulatory chains. Amino acid substitution at two positions yielded enzymes which retained a maximum velocity similar to that of the wild-type enzyme but responded differently from the native enzyme in the presence of regulatory nucleoside triphosphates. A change of zinc coordinate amino acid C109 to histidine and a change of E119 to aspartic acid resulted in enzymes which demonstrated synergistic inhibition by CTP and UTP but not inhibition by CTP in either phosphate buffer or a morpholino-based tri-partate (TP) buffer at pH 7. At pH 8.3, where there is a higher proportion of T-state conformers in the native enzyme, the mutants diverged from their similar kinetic behavior. C109H remained an enzyme which was not inhibited by CTP but was still inhibited by CTP+UTP. E119D was inhibited by both CTP and CTP+UTP. Activation of the mutants by ATP was found to vary either with pH or with phosphate as a buffer component. C109H was activated by ATP in phosphate, while in TP at either pH 7 or 8.3 its activation by ATP was diminished or absent. E119D was activated by ATP in phosphate at pH 7 or in TP at pH 8.3, but not in TP at pH 7. In TP at pH 7, where neither mutant was activated by ATP, the S values and Hill coefficients of the unliganded mutant enzymes resembled those of the ATP-liganded wild-type enzyme. While neither mutation would be predicted to alter the net charge of the holoenzyme, differences in the isoelectric point of the mutants were observed if phosphate was present. This result suggests that the isoelectric point of aspartate transcarbamoylase is conformationally dependent and that the mutants exist in an altered conformation. In addition, the stabilities of both mutant holoenzymes were reduced substantially from those of the wild-type enzyme in 4 M urea. C109H was more stable at pH 8.25 in a Tris buffer; E119D was more stable at pH 7 in the phosphate buffer. Potential effects of these mutations on the active site chemistry and geometry are discussed. PMID- 8476847 TI - Molecular dynamics simulations of the unfolding of apomyoglobin in water. AB - Molecular dynamics simulations of apomyoglobin have been conducted in aqueous solution for 350 ps at 25 degrees C and for 500 ps in two different runs at 85 degrees C. The structures obtained at the higher temperature display properties similar to those of molten globules. Close agreement is obtained between the computed structural models and experimental data on the helical content of both native apomyoglobin and the low-pH unfolding intermediate. The results also suggest explanations for the surprising observations on the effects of mutations at the interface of the A, G, and H helices. Detailed analyses of the final structures and the unfolding pathways at high temperature clearly show that the most stable alpha-helical regions are those in contact with other helices. PMID- 8476848 TI - Complete nucleotide sequence of the antithrombin gene: evidence for homologous recombination causing thrombophilia. AB - Antithrombin is the principle regulator of thrombin and other blood coagulation proteinases. It is a member of the serpin family of proteinase inhibitors. The genomic sequence of the antithrombin locus has been completed, revealing a gene spanning 13,477 base pairs from the transcription start site to the poly(A) addition signal. Nine complete and one partial Alu repeat elements were identified within the introns of the gene, with all but one orientated in the reverse direction. Inherited deficiency of antithrombin is associated with a venous thrombotic tendency. Restriction fragment mapping of the antithrombin genes in an individual with type I antithrombin deficiency identified an intragenic deletion in one allele. Localization of the deletion breakpoints involved restriction analysis and direct sequencing of amplified DNA spanning the deletion site. The deletion removed 2761 base pairs, affecting exon 5 and flanking introns, with the deletion ends contained within the left components of two Alu elements. It is likely, therefore, that the deletion arose by homologous recombination between the two Alu elements. PMID- 8476849 TI - Transforming the Escherichia coli Trp repressor into a site-specific nuclease. AB - The Escherichia coli Trp repressor has been converted into an operator-specific nuclease by alkylating cysteine-49, inserted by site-directed mutagenesis, with 5 (iodoacetamido)-1,10-phenanthroline. In the presence of copper ion and thiol, high yields (> 50%) of double-stranded breaks of DNA are observed after a 20-min reaction. The high cleavage efficiency of this derivatized protein (Trp repressor E49C-OP) can be attributed to the proximity of cysteine-49 to the minor groove, the site of the C-1H of the deoxyribose and the target of the oxidative nuclease activity of (1,10-phenanthroline)copper. Since sequence position 49 is close to the protein's C2 dyad axis and adjacent to the minor groove, Trp repressor E49C OP reacts with the operator DNA near the binding site of this symmetry locus of the protein. The patterns of scission of the trpR, aroH, and trpEDCBA operators (a) confirm the orientation of the repressor to the operator predicted from the X ray study of a cocrystal (Otwinowski et al., 1988) and (b) support the model for tandem binding of the repressor to the trpR, aroH, and trpEDCBA operators based on DNase I footprinting and methylation interference (Kumamoto et al., 1987). There are one, two, and three binding sites for the repressor on the trpR, aroH, and trpEDCBA operators, respectively. In addition to providing a novel approach to studying the interactions of DNA binding proteins, 1,10-phenanthroline derivatized proteins such as Trp repressor E49C-OP may be useful as rare cutters in the analysis of high molecular weight DNAs, especially if their binding specificities can be altered. PMID- 8476850 TI - The acidic phosphoproteins from Saccharomyces cerevisiae ribosomes. NH2-terminal acetylation is a conserved difference between P1 and P2 proteins. AB - Isoelectrofocusing gels of acidic ribosomal proteins from most yeast strains reveal the presence of up to 10 bands which are the product of only 4 genes. The proteins have been characterized by NH2-terminal amino acid sequencing, specific antibodies, HPLC, and by taking advantage of acidic protein-defective yeast strains obtained by gene disruption methods. The four most basic proteins coincide with the phosphorylated and dephosphorylated forms of the YP2 proteins, YP2 alpha and YP2 beta, formerly named L44 and L45. Amino-terminal sequencing has shown that these two polypeptides have free amino-terminal ends starting at the first methionine residue. The bands defined earlier as L44' correspond to the phosphorylated and dephosphorylated processed forms of protein YB1 beta lacking the first eight amino acids. The formation of this truncated YP1 beta form seems to be stimulated by salt during protein extraction and is also favored by some modifications at the amino termini of the protein. On the other hand, the previously uncharacterized band, called Ax, corresponds to an NH2-terminal acetylated form of YP1 beta which starts at the serine in the second position of the nucleotide-derived sequence. Finally, the most acidic band is the phosphorylated product of the fourth acidic protein gene. This protein, called YP1 alpha, which is very poorly stained by silver and Coomassie blue, has not been characterized in detail previously. It is also monophosphorylated in the ribosome and, like YP1 beta, is present as an NH2-terminal acetylated form starting at the second serine residue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476851 TI - GC base sequence recognition by oligo(imidazolecarboxamide) and C-terminus modified analogues of distamycin deduced from circular dichroism, proton nuclear magnetic resonance, and methidiumpropylethylenediaminetetraacetate-iron(II) footprinting studies. AB - The DNA binding properties of a series of imidazole-containing and C-terminus modified analogues 4-7 of distamycin are described. These analogues contain one to four imidazole units, respectively. Data from the ethidium displacement assay showed that these compounds bind in the minor groove of DNA, with the relative order of binding constants of 6 (Im3) > 7 (Im4) > 5 (Im2) > 4 (Im1). The reduced binding constants of these compounds for poly(dA-dT) relative to distamycin, while they still interact strongly with poly(dG-dC), provided evidence of GC sequence acceptance. The preferences for GC-rich sequences by these compounds were established from a combination of circular dichroism (CD) titration, proton nuclear magnetic resonance (1H-NMR), and methidiumpropylethylenediaminetetraacetate-iron(II) [MPE.Fe-(II)] footprinting studies. In the CD studies, these compounds produced significantly larger DNA induced ligand bands with poly(dG-dC) than poly(dA-dT) at comparable ligand concentrations. 1H-NMR studies of the binding of 5 to d-[CATGGCCATG]2 provided further evidence of the recognition of GC sequences by these compounds, and suggested that the ligand was located on the underlined sequence in the minor groove with the C-terminus oriented over the T residue. MPE footprinting studies on a GC-rich BamHI/SalI fragment of pBR322 provided unambiguous evidence for the GC sequence selectivity for some of these compounds. Compounds 4 and 7 produced poor footprints on the gels; however, analogues 5 and 6 gave strong footprints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476852 TI - Mechanism of intercalation into the DNA double helix by ethidium. AB - The mechanism of intercalation into DNA double helices by ethidium has been analyzed by temperature-jump relaxation and stopped-flow measurements using fluorescence detection. Artifacts due to field- or flow-induced alignment have been eliminated by measurements under magic angle conditions; the theoretical basis for suppression of orientation effects resulting from external forces is given for the case of fluorescence measurements. Excluded site effects have been avoided by restriction to low degrees of binding. The temperature-jump relaxation observed for ethidium binding to DNA could be described by single exponentials under most conditions. The reciprocal time constants increased linearly with the DNA concentration, leading to association rate constants of 2.7 x 10(6) M-1 s-1 at 12 degrees C. These rate constants are virtually independent of the DNA chain length for samples with 200, 500, 4228, and 30,000 base pairs, showing that the rate is controlled by reaction and not by a diffusive process. At high DNA concentrations around 200 microM, an additional relaxation effect with an amplitude opposite to the main one is observed which is probably due to some conformational change of the DNA-ethidium complex. The results obtained by stopped-flow measurements are consistent with those from T-jump measurements, but owing to higher amplitudes and better signal to noise ratios, the stopped-flow data clearly require two exponentials for satisfactory representation. The reciprocal time constants for both processes increase linearly with the DNA concentration. The simplest mechanism consistent with this result involves parallel formation of two different complexes with a direct transfer of ethidium between the binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476853 TI - Structural and sequence elements required for the self-cleaving activity of the hepatitis delta virus ribozyme. AB - The hepatitis delta virus (HDV) is a subviral RNA that contains a self-cleaving activity that is similar to the ribozyme activity found in certain plant pathogens. However, the sequences surrounding the cleavage site are unrelated to the hammerhead or hairpin ribozyme motifs, and it is considered to be a distinct ribozyme type. We made site-specific changes within two regions of the smallest contiguous HDV sequence that has optimal activity and kinetically analyzed the data at different temperatures to determine the potential roles of the residues. We distinguish between those changes that affect the rate of catalysis and those that promote the formation of inactive structures. We find that nucleotides +45 to +72 downstream from the cleavage site, which can form a hairpin structure, are dispensable for catalytic activity but that they enhance the cleavage efficiency. Nucleotides +17 to +19 and +28 to +30 form Watson and Crick base pairs that are important for activity, but the actual sequence is not critical. In contrast, the nucleotides between +21 and +26 are important for activity, and they may be involved in significant tertiary interactions. PMID- 8476854 TI - Multiple protein-binding domains and functional cis-elements in the 5'-flanking region of the human pyruvate dehydrogenase alpha-subunit gene. AB - We have characterized the 5'-flanking region of the alpha-subunit gene of the human pyruvate dehydrogenase (E1). DNase I footprinting with rat liver nuclear extracts identified 7 major protein-binding domains termed P1 through P7 in a 796 base pair DNA fragment (base pairs -763 to +33). P1 through P4 are clustered in the -221/+33 region. These protein-binding domains contain several known consensus sequences such as a TATA box, CAAT box, Sp1, and CRE, which all have previously been implicated in the constitutive transcription of several genes. Oligonucleotide competition studies indicate that oligonucleotides specific for CTF/NF-1 and Sp1 displaced the nuclear proteins bound to the CAAT box (within P3) and an Sp1 site (within P4), respectively. Several other well-characterized and purified transactivators (c-Fos, c-Jun, C/EBP, AP-2, and Sp1) have been shown to bind to the -221/+33 region. Other elements located upstream of the -221/+33 region, which includes nuclease protection domains P5-P7, are required for enhanced promoter activity of the 796 bp sequence. Promoter activity was measured by transient expression of a chloramphenicol acetyltransferase gene ligated to deletion fragments of the 5'-flanking region. Crucial element(s) for promoter activity and complex DNA-nuclear protein interactions were confined within a region spanning -221/+33. This region also retained more than 75% of the promoter activity of the 796 bp sequence. Additionally, this promoter region shows characteristics of both facultative and housekeeping gene promoters, suggesting complex transcriptional regulation. PMID- 8476855 TI - Tests of a model for promoter recognition by T7 RNA polymerase: thymine methyl group contacts. AB - The DNA-dependent RNA polymerase from bacteriophage T7 is highly specific for a 17 base promoter sequence. Interactions between T7 RNA polymerase and its promoter DNA have been probed using modified oligonucleotides and a steady-state kinetic assay. The incorporation of deoxyuridine in place of thymidine at individual sites in the promoter sequence results in the replacement of an exocyclic methyl group by hydrogen (effectively removing the thymine methyl). This substitution has been placed individually at each of the thymines in the T7 consensus promoter. Many of these substitutions do not affect binding or catalysis; however, the thymine methyl group at position-6 is critical to recognition. The kinetic parameter Km increases approximately 10-fold while kcat is only slightly affected, suggesting that this thymine methyl is critical to binding specificity, but not to the kinetics of initiation. Two methyl groups near the start site on the template strand (at positions -1 and -3) also contribute to promoter specificity, while nearby methyl groups on the nontemplate strand do not. The implications of these results are discussed with respect to recent models for promoter binding. PMID- 8476856 TI - Identification of specific contacts in T3 RNA polymerase-promoter interactions: kinetic analysis using small synthetic promoters. AB - The T7, T3, and SP6 RNA polymerases recognize very similar, yet distinct, promoter sequences. The high homology among the promoter sequences suggests that differential promoter recognition must derive from relatively small changes in the protein. Steady-state kinetic analyses of transcription from the T3 consensus promoter and from promoters modified in the region critical to specific recognition reveal details concerning which functional groups contribute to this recognition. Modifications include base pair substitutions, single base substitutions (mismatches), and simple functional group modifications at unique sites in the promoter. The results show that T3 RNA polymerase recognizes the amino group on the nontemplate cytidine in the major groove at position -10, while the identity of the base on the template strand is less critical to binding. In contrast, recognition at position -11 allows a greater range of modifications and seems to have a more complex recognition. The results do not seem to be consistent with a single recognition contact at this position; however, some groups may be ruled out as simple recognition contacts. While major groove modifications weaken binding at positions -10 and -11, the removal of an exocyclic amino group from the minor groove at either position does not disrupt binding, further supporting a model for promoter recognition in which the enzyme binds to one face of closed duplex DNA in this region. The effects of these changes in the DNA structure on the kinetics of initiation are compared to complementary results from the T7 system. PMID- 8476857 TI - Kinetic analysis of T7 RNA polymerase transcription initiation from promoters containing single-stranded regions. AB - T7 RNA polymerase is highly specific for the initiation of transcription from a relatively small consensus promoter sequence. Previous footprinting studies suggested that the enzyme binds specifically to a fully closed duplex form of the promoter, recognizing functional groups along one face of the helix [Muller, D. K., Martin, C. T., & Coleman, J. E. (1989) Biochemistry 28, 3306-3313]. Steady state kinetic analysis of oligonucleotide-based promoters shows that removal of the nontemplate strand completely within the message region of the DNA (positions +1 through +5) results in no change in binding (as reflected in the parameter Km) and a 2-fold increase in kinetics (as reflected in kcat). Further deletion of the nontemplate strand as far upstream as position -4 has no effect on binding, and although deletion upstream through position -6 weakens binding, specific initiation continues at a high rate. The temperature dependence of the initiation kinetics shows a single apparent activation energy of approximately 26 kcal/mol for the fully duplex promoter. Similar measurements on the promoter lacking the nontemplate strand in the message region show that less than 10% of this barrier is related to melting of the downstream region of the promoter. These results lead us to revise the previous model for recognition to include specific binding to a form of the promoter which is duplex upstream of about position -6 and melted downstream through the start site. Within the melted region, the polymerase interacts significantly only with the template strand of the promoter DNA. PMID- 8476858 TI - Molecular mechanisms regulating the production of collagenase and TIMP in U937 cells: evidence for involvement of delayed transcriptional activation and enhanced mRNA stability. AB - We have used the human promonocyte-like U937 cell line as a model to study the regulation of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP) during mononuclear phagocyte development. Our results show that differentiation of U937 cells with exposure to 12-O-tetradecanoylphorbol 13 acetate (TPA) induces a temporally delayed (16-24 h) but marked increase in the biosynthesis and secretion of interstitial collagenase and TIMP. Similarly, steady-state mRNA levels for both proteins rose dramatically during the period of exposure, but again after considerable time delay (12-16 h). For interstitial collagenase, induction was transcriptionally regulated as demonstrated by nuclear run-on experiments, and required the synthesis of proteins as indicated by cycloheximide treatment. However, transcriptional activation of collagenase was never observed prior to 10-12 h; since c-fos is rapidly induced in U937 cells and largely disappears by 2 h (Mitchell et al., 1985), our data strongly suggest that collagenase induction in this system cannot be explained simply or entirely by an AP-1-dependent mechanism. Although TIMP steady-state mRNA levels also increased substantially with cellular differentiation, no transcription was detected by run on experiments. However, TPA exposure markedly prolonged the half-life of TIMP mRNA from 4 h to > 20 h. While cycloheximide treatment completely blocked TPA mediated induction of collagenase mRNA, it only marginally interfered with simultaneously induced TIMP mRNA levels. Our results demonstrate that differentiation of U937 monocytic cells is accompanied by markedly enhanced production of both interstitial collagenase and TIMP. However, there are multiple, and perhaps differing, molecular mechanisms regulating these responses. PMID- 8476859 TI - Cloning, sequencing, and expression in Escherichia coli of the gene coding for malate dehydrogenase of the extremely halophilic archaebacterium Haloarcula marismortui. AB - The gene coding for the enzyme malate dehydrogenase (MDH) of the extremely halophilic archaebacterium Haloarcula marismortui was isolated and sequenced. The enzyme is composed of 303 amino acids, and its molecular mass is 32,638 Da. The deduced amino acid sequence of the enzyme was found to be more similar to the sequence of L-lactate dehydrogenase (L-LDH) from various sources than to the sequence of other MDHs. The structural gene was cloned in the Escherichia coli expression vector pET11a, and large amounts of a soluble but inactive form of the enzyme were produced upon its induction. Activation of the enzyme was obtained by increasing the salt concentration to 3 M NaCl. The recombinant protein was purified to homogeneity and shown to be indistinguishable from the native enzyme isolated from halobacteria. These findings present the first example of the successful expression of a halobacterial gene coding for a soluble protein in Escherichia coli and its recovery as a functional enzyme. Site-directed mutagenesis was employed to modify Arg100 on the enzyme to Gln. This modification produced an enzyme that has considerably higher specificity for pyruvate (the substrate of L-LDH) than for oxaloacetate (the substrate of MDH). The mutation also caused a modification in the relative activities of the enzyme at different salt concentrations. The greater similarity of the amino acid sequence of the halobacterial MDH to that of L-LDHs than to that of MDHs sheds light on the molecular evolution of these enzymes. PMID- 8476860 TI - Three-state denaturation of DnaK induced by guanidine hydrochloride. Evidence for an expandable intermediate. AB - The denaturation of the heat shock protein DnaK induced by guanidine hydrochloride (Gdn-HCl) was investigated by circular dichroism, fluorescence, size-exclusion HPLC, and dynamic light scattering. DnaK unfolding takes place in two discrete steps. The midpoint (Cm) of the first transition (0.5 M) was shifted to higher denaturant concentrations (0.8 M) in the presence of Mg/ADP or Mg/ATP, whereas the second transition (Cm = 1.6 M) was unaffected by nucleotides. An intermediate state which continuously expands with increasing Gdn.HCl concentration was observed; its relation to molten globules is discussed. In addition, a direct correlation between molecular volume and ellipticity at 222 nm was found, regardless of the conformational state (native, intermediate, unfolded); the implications of these findings are discussed. The unfolding of DnaK is best explained by a hierarchical model of unfolding. PMID- 8476861 TI - Engineered disulfide bonds as probes of the folding pathway of barnase: increasing the stability of proteins against the rate of denaturation. AB - Disulfide bridges have been introduced into barnase to act as probes of folding. One disulfide (between residues 85 and 102) links two loops known to pack together early in the folding pathway. A second disulfide bond (between residues 43 and 80) links two elements of secondary structure known to pack together only after the rate-determining step of folding. The disulfide-bridged proteins are more stable than wild-type by 4.1 and 1.2 kcal mol-1, respectively. The kinetics of unfolding and refolding of the mutant proteins has been measured, and a comparison of the disulfide proteins and their corresponding dithiol forms has been made by use of thermodynamic cycles. These data have been used to construct folding profiles of the disulfide proteins. The disulfide bond engineered into the part of the protein that folds early confers stability upon the intermediate and transition states of folding. The protein with a disulfide bond connecting parts of the protein that fold late is not stabilized until the protein reaches its final folded form. Conversely, in the unfolding pathway, the rate of unfolding of this mutant is lowered considerably. This points to a method of decreasing the rate of denaturation of proteins that are used in medical and biotechnological applications: elements of structure that unfold in or before the rate-determining step of overall unfolding may be stabilized and so slow down the overall unfolding process. The barnase mutant linked between Cys 43 and Cys 80, for example, unfolds 20 times slower than wild-type and 170 times slower than the reduced protein. PMID- 8476862 TI - The activity of the tissue inhibitors of metalloproteinases is regulated by C terminal domain interactions: a kinetic analysis of the inhibition of gelatinase A. AB - The cloning and expression of the full-length tissue inhibitor of metalloproteinase 2 (TIMP-2), delta 187-194TIMP-2, and delta 128-194TIMP-2 and the purification of these inhibitors and a cleaved version of TIMP-2 lacking nine C-terminal amino acids (delta 186-194TIMP-2) are described. The mechanism of inhibition of gelatinase A by the TIMPs was investigated by comparing the kinetics of association of TIMP-1, TIMP-2, the C-terminal deletions, and the mutants of both TIMPs which consisted of the N-terminal domain only. The full length TIMPs inhibited gelatinase A rapidly with association constants of 3.2 x 10(6) M-1 s-1 for TIMP-1 and 2.1 x 10(7) M-1 s-1 for TIMP-2 at I = 0.2. The C terminal peptide of TIMP-2 is proposed to exist as an exposed "tail" responsible for binding to progelatinase A and for increasing the rate of inhibition of active gelatinase A through electrostatic interactions with the C-terminal domain of the enzyme. The C-terminal domains of both TIMP-1 and TIMP-2 participate in low-affinity interactions with the C-terminal domain of gelatinase A which increase the rate of association by a factor of about 100 in both cases. PMID- 8476863 TI - Direct evidence for the exploitation of an alpha-helix in the catalytic mechanism of triosephosphate isomerase. AB - In previous work, we have shown that the first (and, presumably, the second) pKa of the active-site histidine-95 in triosephosphate isomerase has been lowered by about 2 units [Lodi, P. J., & Knowles, J. R. (1991) Biochemistry 30, 6948-6956]. One reason for the perturbed pKa of this residue appears to be its location at the N-terminus of a short alpha-helix that runs from residues 95 to 102. Fortuitously, the residue at the C-terminus of this helix is also a histidine residue (histidine-103), and the existence of a histidine side chain at each end has allowed us directly to implicate the helix in the perturbation of the pKa value of histidine-95. 15N NMR titration studies of the native enzyme and 13C NMR titration studies of the denatured enzyme show that while the pKa of histidine-95 is lowered by a least 2 units in the folded versus the unfolded state, the pKa of histidine-103 is raised by about 0.6 unit on protein folding. These complementary effects on the pKa values of histidine-95 and histidine-103 suggest that the alpha-helix is indeed responsible for the perturbation of the pKa values. The larger effect on the pKa of histidine-95 is readily rationalized in terms of the local structure of the enzyme. The disparity in the perturbation for the two histidine side chains illustrates how an alpha-helix can be functionally utilized by proteins, directly to affect (as in the present case) the chemistry of catalysis by an enzyme. PMID- 8476864 TI - Analysis of enzyme specificity by multiple substrate kinetics. AB - Multiple approaches for screening large sets of compounds for a specific function are of growing interest. The use of substrate mixtures to characterize the specificity of enzymes has been limited so far to compounds with similar kinetic parameters, because the data were analyzed by applying the kinetics of two competing substrates. In this study we introduce a statistical method for the analysis of reactions with many competing substrates which makes use of the specific features of multiple substrate kinetics. It is assumed that the relative concentrations of all substrates in a mixture can be monitored by high performance liquid chromatography or a similar technique. Relative second-order rate constants, i.e., kcat/KM values, can be calculated for all substrates in the mixture from the resulting data set. The calculation uses the fact that there is a relationship between the concentrations of all pairs of substrates in the mixture. As a result, the precision of the calculated parameters is increased and the range of kinetic constants that can be obtained from one experiment is considerably expanded. Simulations demonstrate that the precision in the kinetic parameters increases with the number of substrates in the mixture. In fact, estimation of ratios of rate constants can be improved (or made possible) for substrates with order of magnitude differences in reactivity by adding "dummy" substrates with intermediate reactivities, even though the rate constants for dummy substrates are themselves of no intrinsic interest. PMID- 8476865 TI - Mapping the S' subsites of serine proteases using acyl transfer to mixtures of peptide nucleophiles. AB - We have developed a rapid and convenient procedure for the characterization of the S' subsite specificity of serine proteases. A mixture of peptide nucleophiles is incubated with the enzyme in the presence of excess of a specific ester substrate. The decrease in each nucleophile concentration is monitored by high performance liquid chromatography analysis of the dansylated mixture. Relative kinetic parameters for each nucleophile in the mixture are then calculated using a new statistical algorithm that relates all pairs of nucleophiles. As a first application, we investigated the S'1 subsite specificity of chymotrypsin, trypsin, and a recently described trypsin mutant, Tr-->Ch[S1 + L1 + L2] with chymotrypsin-like primary specificity [Hedstrom, L., Szilagyi, L., & Rutter, W. J. (1992) Science 255, 1249-1253]. For this purpose 21 peptide nucleophiles of the general structure H-Xaa-Ala-Ala-Ala-Ala-NH2 were prepared by multiple solid phase synthesis, where Xaa represents D-alanine, citrulline, and all natural amino acids except cysteine. Relative second-order rate constants for the enzyme catalyzed acyl transfer to these nucleophiles were determined over a range of 10(2). Chymotrypsin and trypsin have markedly different S'1 specificities. The order of preference in chymotrypsin-catalyzed acyl transfer reactions is positively charged > aliphatic > aromatic >> negatively charged, D-Ala, Pro P'1 side chain. Trypsin prefers hydrophobic residues, but like chymotrypsin aliphatic residues are better than aromatic residues in P'1 position. The S'1 specificity of the mutant Tr-->Ch[S1 + L1 + L2] is similar to the specificity of trypsin; however, P'1 aromatic residues have low reactivity characteristic of chymotrypsin. PMID- 8476867 TI - Pulmonary surfactant-associated protein SP-B has little effect on acyl chains in dipalmitoylphosphatidylcholine dispersions. AB - Synthetic human pulmonary surfactant-associated protein SP-B has been interacted with chain-perdeuterated dipalmitoylphosphatidylcholine (DPPC-d62) in aqueous dispersions, and the dispersions were investigated by magnetic resonance spectroscopy. The protein caused only small perturbations of the deuterium magnetic resonance spectra in the gel and liquid-crystal states. In an amount of 11% by weight in DPPC, it produced a small reduction in the magnitude of the first moments of the spectra in the gel and a small increase (approximately 5%) in their magnitude in the liquid crystal. In the liquid crystal the protein was observed to cause a similar effect on all portions of the acyl chain, as observed by its proportional shifting of splittings obtained from "dePaked" spectra. Using data from circular dichroism spectra, the protein was found to be about 45% alpha helical in methanol and in DPPC dispersions. alpha-Helical content was not significantly changed by the presence of 2 mM calcium or by the packing state of the acyl chains. The presence of the protein enhanced the adsorption rate of lipid into the air-water interface when dispersions of lipids or lipid plus SP-B were injected below the interface. The results could be consistent with the protein interacting with the lipid near the head groups or arranging itself around the edges of bilayer discs, or a combination of the two orientations. PMID- 8476866 TI - Effect of Na+ and nucleotide on the stability of solubilized Ca(2+)-free Ca ATPase from scallop sarcoplasmic reticulum. AB - In membranous scallop sarcoplasmic reticulum, the alkali metal cations Na+ and K+ and nucleotide together promote dimer formation by the Ca(2+)-free Ca-ATPase and stabilize the enzyme activity [Kalabokis, V. N., Bozzola, J. J., Castellani, L., & Hardwicke, P. M. D. (1991) J. Biol. Chem. 266, 22044-22050]. The dependence of stabilization of the Ca(2+)-free membranous scallop Ca-ATPase on Na+ concentration does not show saturation and may involve several superimposed effects. In order to assess the contribution of dimer toward stabilization, i.e., determine the relative importance of intra- and intermolecular effects on stabilization, the influence of varying Na+ concentration and nucleotide on the decay of enzyme activity of the Ca(2+)-free detergent-solubilized Ca-ATPase was studied. Loss of enzyme activity on removal of Ca2+ with EGTA was associated with loss of capacity for phosphorylation by ATP, a Ca(2+)-dependent function. Stabilization of the soluble Ca(2+)-free enzyme by Na+ showed major differences from that seen with the membranous enzyme. The extent of stabilization of the Ca(2+)-free soluble enzyme by Na+ showed clear saturation with increasing Na+ concentration. In contrast to the Ca(2+)-free membranous enzyme, which is inactivated at pH 7.0 with biphasic first-order kinetics, loss of enzymatic function by the solubilized Ca-ATPase at pH 6.92, 0 degrees C, followed monophasic first-order kinetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476868 TI - Properties of a high-potential flavin analogue and its use as an active site probe with clostridial flavodoxin. AB - The reduction potential of flavin bearing a methylsulfonyl moiety (MeSO2) in place of a methyl group at position 8 is increased by more than 150 mV as compared with normal flavin. This substitution is accompanied by a substantial increase in reactivity with various reductants, including NADH, and greatly (10(3)-fold) enhanced susceptibility toward nucleophilic attack by sulfite at N(5). 1,5-Dihydro-8-(methylsulfonyl)riboflavin exhibits two intense, well resolved absorption bands (lambda max = 310, 362 nm) in a region where most other reduced flavins exhibit weak, characterless absorption. This unusual spectrum is attributable to a shift of pi-electron density from the N(5) atom into the benzene ring. It is observed only with reduced flavins bearing a strongly electronegative substituent (MeSO2, CN) at the 8-position. The effect is abolished by replacing the hydrogen at N(5) with a bulky group, like sulfite, which interferes with sp2 hybridization at N(5). Reaction of 8-MeSO2-substituted flavins with thiols results in nucleophilic displacement of MeSO2- in a reaction that is about 10(3)-fold faster than an analogous nucleophilic displacement reaction observed with 8-halo-substituted flavins. The flavin ring acts as a redox switch in controlling electrophilicity at the 8-position, as judged by the fact that the displacement reactions are observed only with the oxidized flavins. Initial studies to evaluate 8-MeSO2-substituted flavins as active site probes were conducted with flavodoxin from Clostridium beijerinckii MP. 8-MeSO2FMN is rapidly bound to apoflavodoxin, accompanied by absorbance and fluorescence changes similar to those observed for FMN binding. 1,5-Dihydro-8-MeSO2FMN flavodoxin exhibits spectral properties (lambda max = 323, 382 nm) similar to those of the corresponding free flavin, except for a bathochromic shift due to a change in the polarity of the flavin environment. As judged by peak resolution and intensity, the spectral properties of 1,5-dihydro-FMN flavodoxin (lambda max = 311, 362 nm) appear to lie about midway between those observed for the free 1,5 dihydro forms of FMN versus 8-MeSO2FMN. This suggests that the protein environment may favor enhanced resonance delocalization of pi-electron density into the benzene ring of bound 1,5-dihydro-FMN, as compared with the free flavin. This hypothesis is consistent with previous NMR studies and with a proposal that electron transfer from reduced flavodoxin to other redox proteins occurs through this region of the ring. 8-MeSO2FMN bound to flavodoxin reacts readily with exogenous thiols but does not react with sulfite.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8476869 TI - Functionally important domains of the large hydrophilic loop of CP47 as probed by oligonucleotide-directed mutagenesis in Synechocystis sp. PCC 6803. AB - The chlorophyll a-binding protein CP47 serves as core antenna to photosystem II (PS II). The predicted topology of CP47 exhibits six membrane-spanning regions and a large hydrophilic loop (loop E) which roughly includes 200 residues (255 455) and is presumably exposed to the lumenal side of the thylakoid membrane. Several lines of experimental evidence suggest that loop E might be involved in binding or stabilizing functional manganese in the catalytic site of water oxidation or in interacting with the extrinsic PS II-O protein (the 33-kDa manganese-stabilizing protein). To scan loop E for functionally important domains, oligonucleotide-directed mutagenesis has been used to introduce deletions of 3-8 residues in conserved and charged regions of loop E. In addition, one single-site mutation of the only histidine present in loop E was created (H343L). Domains deleted in delta 1 (I265-F268), delta 2 (T271-K277), delta 4 (T304-L309), delta 5 (F311-N317), and delta 12 (D440-P447) are required for stable assembly of functional PS II complexes. Deletion of domains delta 3 (K277-E283) and delta 11 (R422-E428) significantly reduces the level of assembled PS II and impairs photoautotrophic growth and oxygen evolution. Deletion of domain delta 8 (A373-D380) enhances the susceptibility to photoinhibition. In contrast, deletion of domains delta 6 (G333-I336), delta 7 (K347-R352), delta 9 (V392-Q394), and delta 10 (D416-F420) and mutation of H343 to leucine do not seem to severly interrupt PS II structure and function, although all mutants exhibit a slightly decreased stability of PS II as compared to the wild type. Thus, selected domains of the large hydrophilic loop of CP47 are important for PS II structure and function. With respect to possible sites of interaction between loop E of CP47 and the extrinsic PS II-O protein, our results indicate that none of the deletions in the region from residue 330 to 420 (delta 6, delta 7, delta 8, delta 9, delta 10) completely interrupts a functional association of the manganese-stabilizing protein to PS II, although the binding characteristics might be changed in some cases. PMID- 8476870 TI - Structure-function relationship of a recombinant human galactoside-binding protein. AB - A galactoside-binding lectin (hL-31) containing a collagen-like sequence was identified in human tumor cells. It was found to be the homologue of the IgE binding protein, the macrophage cell-surface Mac-2 antigen, and the murine CBP35, RL-29, and mL-34 lectins. Here we report on the expression in Escherichia coli and functional analysis of recombinant hL-31 (rhL-31). The rhL-31 was purified in one step through an asialofetuin affinity column. The rhL-31 was reactive to anti lectin antibodies and retained its lactose-dependent hemagglutination of trypsin treated glutaraldehyde-fixed rabbit erythrocytes. The rhL-31 elutes from an affinity column as a 31-kDa monomer and undergoes homodimerization at relatively high protein concentrations, comparable to those used to mediate hemagglutination. Electron microscopy showed that the rhL-31 appears as a Y shaped structure. Lactoperoxidase-catalyzed iodination of murine tumor cell surface proteins followed by collagenase treatment revealed that the lectin is probably a peripheral membrane protein whereby both the amino and the carboxy termini are exposed on the outer cell membrane. These results point to the membrane disposition and orientation of the lectin and suggest a mechanism for a structure-function relationship of lectin activity. PMID- 8476871 TI - Mechanisms of mutation by oxidative DNA damage: reduced fidelity of mammalian DNA polymerase beta. AB - Reactive oxygen species, produced in cells by a variety of mechanisms, damage DNA and cause mutations. To characterize the types of mutations produced in mammalian cells, we copied DNA damaged by reactive oxygen species with mammalian DNA polymerase beta. Double-stranded circular M13mp2 DNA containing a 361-nucleotide single-stranded gap within the lacZ gene was damaged by aerobic incubation with Fe2+ and H2O2. The gap then was filled by purified recombinant rat DNA polymerase beta, and the DNA was transfected into Escherichia coli. Mutations within the nonessential lacZ gene for beta-galactosidase were identified by reduced alpha complementation. In this system, oxidative damage increased the mutation frequency within the target region by an average of 4.3-fold. At certain sites, the base substitution rate is nearly 300 times greater than would be expected to result from a random distribution of damage. The oxidatively induced mutations fall into two categories: those apparently caused by direct miscoding of modified DNA and those associated with enhanced misincorporation at prexisting polymerase specific hot spots. The latter group may be due to a conformational change in the DNA caused by oxidative modification and could be indicative of a novel mutagenic mechanism. PMID- 8476872 TI - Cholesterol screening in the adolescent. AB - Guidelines for screening populations for hypercholesterolemia are controversial. In pediatric patients, screening has been targeted to those with a family history of hypercholesterolemia or early myocardial infarction. Because specific guidelines for adolescents have not been developed, we undertook a study of cholesterol screening in 224 consecutive patients (mean age, 14.8 +/- 2.2 years; range, 11-20 years). In this study, 33 (14.7%) adolescents had levels above 185 mg/dL; 71 (32.7%) of the patients reported a positive family history for early myocardial infarction or elevated lipids. A positive family history obtained from the adolescent patient had a 36% sensitivity, 69% specificity, 17% positive predictive value, and an 87% negative predictive value compared with elevated cholesterol level. A positive history reported by the parent had a 65% sensitivity, 46% specificity, 16% positive predictive value, and an 89% negative predictive value. A positive family history obtained from either parent or adolescent had a 45% sensitivity, 69% specificity, 19% positive predicative value, and 89% negative predictive value. Family history by the adolescent was significantly different from parental history (p < 0.001). Family history is a poor predictor for cholesterol level in adolescents. PMID- 8476873 TI - A developmental approach to sexuality education: implications for medical practice. AB - Medical professionals are increasingly expected to address issues of sexuality and acquired immunodeficiency syndrome (AIDS) with young patients and their parents. Focus group interviews were conducted with parents (n = 43) and adolescents (n = 800) to determine the preferred physician role regarding families and sexual development. Parents believed that a physician was an appropriate expert to assist in preventing negative risk behaviors (e.g., drugs, alcohol, sexual intercourse) and emphasized the importance of the physician developing a comfortable relationship early on with parents and youth to allow for reciprocal dialogue about sensitive topics. Parents also commented that physicians generally appeared uncomfortable when discussing personal issues (viz., sexuality) and frequently lacked communication skills (e.g., use of open ended questions or statements) to foster conversation. Youth identified physicians as a logical source of information about sexuality but felt hesitant to ask questions that might prompt value-based discussion. Youth also expressed concern about confidentiality in the doctor-patient relationship. Adolescents desired physicians to be more "askable" than they are perceived to be. Guidelines are offered for strengthening office interactions and improving communication skills. PMID- 8476874 TI - A pilot study of AIDS education and counseling of high-risk adolescents in an office setting. AB - Little is known about interventions in office practices aimed toward reducing behaviors that put adolescents at risk for human immunodeficiency virus (HIV) acquisition. We therefore targeted a pilot study of HIV education and counseling to high-risk adolescents. Ninety adolescent patients (mean age, 17.6 +/- 2.0 years) were interviewed in a hospital-based adolescent clinic by two physicians and randomized to two groups: 1) a standard care group that was interviewed about high-risk behaviors at 0 and 2 months; and 2) an intervention group that was similarly interviewed but was also given a detailed discussion about HIV risks and prevention. At follow-up (mean, 2.6 +/- 0.8 months), 25% of patients reported less sexual activity (standard care, 32%; intervention, 18%) toward a trend. The reduction in mean number of partners per month was 0.4 +/- 0.9, (p = 0.0001). Fifty-four percent of the patients reported that they used condoms more often than previously with no significant difference between the two groups. Use of condoms ("always use") increased in both groups significantly (p = 0.03 standard care, p = 0.02 intervention). Use of condoms at last intercourse increased in the intervention group (37% to 42%, p = 0.03). In the interval, there were no significant differences between the groups in the number of newly diagnosed sexually transmitted diseases or in the number of patients seeking HIV testing. The number of patients stating that they shared needles decreased from 3 to 0. Both the intervention and standard care groups reported a reduction in high-risk behaviors that was temporally related to the discussion of this subject in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476875 TI - The SAPHO syndrome in a 16-year-old boy: coincidence of acne conglobata and osteoarthritis. AB - A 16-year-old boy developed arthritis and osteitis (anterior thoracic wall, ankle of left foot, spinal column) within 5 weeks of an exacerbation of acne. Both the local skin condition and the locomotory system improved after treatment, but sternocostoclavicular hyperostosis persisted. The syndrome of acne, pustulosis, hyperostosis, and osteitis (SAPHO syndrome) identified in 1987, represents an entity usually classified as one of the seronegative spondylarthrites close to ankylosing spondylarthritis and psoriatic arthritis. PMID- 8476876 TI - The four "R's"--the need for research in the schools. PMID- 8476877 TI - Substance use among adolescents with diabetes mellitus: preliminary findings. AB - Alcohol and drug use frequency was assessed by means of an anonymous, self administered questionnaire in 79 diabetic adolescents who attended a diabetic sleep away camp. More than half of the participants reported using tobacco or alcohol at least once and 12%-25% reported greater that five times use in their lifetime. The overall frequency of drug and alcohol use was less than the general adolescent population. A modified Michigan Alcohol Screening Test (MAST) was used to evaluate abnormal drinking patterns, and 40%-50% of 12- and 16-year-old campers had an abnormal score, indicating that almost one-quarter of diabetic teens drink dangerously. There was a high correlation between campers who use drugs or alcohol and a positive family history of alcohol or substance abuse. Few campers perceived alcohol or drug use to affect their diabetic control, and the majority believed their control to be good to excellent, thus demonstrating the impact of denial in diabetic adolescent substance use. Adolescent diabetic assessments should include a psychosocial history, with emphasis on patterns of substance use, family substance abuse, and use of the MAST to identify high-risk individuals. PMID- 8476878 TI - Changes in adolescents' knowledge and attitudes about AIDS over the course of the AIDS epidemic. AB - We compared AIDS-related attitudes of junior and senior high school students from 1988 to 1991 and across grade level to examine how effectively schools are addressing AIDS. Attitudes measured included knowledge and social anxiety about AIDS, as well as perceptions of vulnerability to HIV infection. Junior high school students (grades 7-9) were sampled three times, from 1989 to 1991. High school students (grades 10-12) were sampled four times, from 1988 to 1991. The 1991 junior high school sample had lower AIDS knowledge scores than the 1989 sample. Conversely, the 1991 high school sample had more accurate knowledge than earlier groups. With respect to grade level, 9th graders had more accurate knowledge than 7th and 8th graders, but knowledge did not increase from 10th through 12th grade. Anxiety about interacting with a person with AIDS and perceptions of vulnerability to HIV infection were unrelated to either sampling time or grade level. It is concluded that it will be important to redouble efforts to educate adolescents about AIDS and that particular attention needs to be paid to young adolescents. PMID- 8476879 TI - School-based clinic use and school performance. AB - School-based health clinics (SBCs) have been promoted as an innovative approach to providing adolescent health care. The present study examined the effect of a SBC on academic success. We studied the effect of clinic registration and use on students' absence, suspension, withdrawal, and graduation or promotion rates in an alternative high school for students who were not able to succeed in traditional educational programs. On average, these 322 high-risk students attended school only 56% of the time; 24% were suspended; and only 26% graduated or were promoted. The 189 (59%) students who were registered to use the clinic and the 159 (49%) who actually used the clinic were as likely to be absent or to be suspended as non-registered students. However, students who used the clinic were significantly more likely to stay in school, and to graduate or be promoted than students who were not registered for the clinic. This relationship was strongest for black males; those who used the clinic were nearly three times [odds ratio = 0.35; 95% confidence interval (CI) = (0.16-0.78)] more likely to stay in school than those who did not use the clinic. In multiple linear regression models predicting school performance, only clinic use and percent of enrolled days absent were significantly associated with graduation/promotion, and these two variables predicted 23% of the variance in promotion status. PMID- 8476880 TI - Parental response to identification of elevated blood pressure or cholesterol following school-based screening. AB - The objective of this study was to identify factors that influenced compliance with a recommendation for reevaluation of an elevated cholesterol or blood pressure level following a school-based screening examination. A questionnaire was developed and mailed to parents of 103 5th- through 8th-grade students who had received such a recommendation. A total of 72 usable questionnaires were returned. There were no significant physiologic, health, or demographic differences between the respondents and the nonrespondents. Of the respondents, 38 (53%) had their child's cholesterol or blood pressure level reevaluated. There were no differences in mean levels of total cholesterol or blood pressure between those reevaluated and those who were not. The factor most often associated with compliance was parents' reported concern about their children's health. Of note was the apparent lack of action by many physicians when presented with blood pressure and cholesterol values above recommended levels. Further study is needed to determine appropriate interventions to enhance compliance. PMID- 8476881 TI - Immunofluorescence of endomyocardial biopsy specimens: methods and interpretation. AB - On the basis of our experience with prospective observation of immunofluorescence microscopy in 5775 biopsy specimens from 335 consecutively followed heart transplant cases, we describe the immunofluorescent method in detail and the potential artifacts and method of interpretation of the findings. A strategy for use of the method on the basis of the experience of the authors is proposed. PMID- 8476882 TI - Laboratory-clinical correlates of time-associated lesions in the vascular immunopathology of human cardiac allografts. AB - Ninety cardiac allograft recipients were studied for clinical and functional parameters during a 40-month period. Baseline histologic and immunocytochemical data were obtained from donors' hearts before transplantation, and serial endomyocardial biopsy specimens were studied histologically for cellular infiltrates and immunocytochemically for complement and immunoglobulin deposits and for components of the hemostatic, fibrinolytic, and natural anticoagulant pathways. Results were grouped according to the time from transplantation: the first 3 months, 4 to 21 months, and 22 to 40 months. Each group was evaluated for most frequently obtained immunocytochemical findings and results relevant to clinical-laboratory cooperation in patient management. During the first 3 months, findings of biopsy specimens from allografts that subsequently were going to be problem cases revealed depleted tissue plasminogen activator in arteriolar smooth muscle cells, and recipient IgM that was deposited on donor endothelium of stable grafts was diminished or absent in unstable allografts. In addition, vascular deposits of activated complement components were identified in 50 of 70 allografts. From 4 through 21 months after transplantation, vascular deposits of complement rarely were identified (even in patients who previously had positive biopsy specimens), and the principal vascular lesion was fibrin deposits with impaired anticoagulant pathways and inadequate fibrinolysis, usually without associated cellular infiltrates. From 22 through 40 months after transplantation, the principal vascular lesion was graft-induced atherosclerosis. These immunocytochemically defined qualitative and quantitative changes in unstable or failing allografts form a time-related spectrum of lesions that encompasses the emerging diagnostic entity of vascular rejection. PMID- 8476883 TI - Vascular rejection in heart transplantation: clinical correlation, treatment options, and future considerations. AB - Vascular rejection injures the vascular endothelium in cardiac allografts in the absence of significant intramyocardial lymphocytic infiltration. When compared with cellular rejection, vascular rejection occurs earlier after transplantation, is more resistant to immunosuppressive augmentation, causes more allograft dysfunction, and is associated with a higher frequency of allograft loss. Between January 1990 and October 1992, acute hemodynamically significant vascular rejection developed in 13 of 170 patients (8%). Endomyocardial biopsy specimens revealed the typical findings of endothelial cell activation, immune complex deposition, and interstitial fibrin deposition in the absence of significant lymphocytic infiltration. All patients had clinical evidence of allograft dysfunction. In addition to high-dose corticosteroids, all patients received cyclophosphamide as an oral pulse for 4 days and underwent plasmapheresis for 3 consecutive days. Eight patients received OKT3 (n = 6) or antilymphoblast globulin (n = 2), and nine patients underwent systemic anticoagulation. Six patients required inotropic therapy for hemodynamic instability. Although one patient died during the initial episode, rejection resolved and left ventricular function returned to normal in 12 of 13 patients. However, vascular rejection recurred in three patients, two of whom subsequently died. Two other patients died during late follow-up because of noncompliance. Eight patients remain alive with normal allograft function and angiographically normal coronary arteries. Whereas the addition of cyclophosphamide and plasmapheresis may improve the outcome of vascular rejection, the results of treatment with currently available treatment modalities remain unacceptably poor. PMID- 8476884 TI - Role of humoral immunity in acute cardiac allograft dysfunction. AB - To elucidate the pathogenic mechanisms of acute allograft dysfunction that is not caused by acute cellular rejection, we have studied the clinical and immunopathologic characteristics of 11 heart transplant recipients who had acute allograft dysfunction in the absence of interstitial mononuclear cell infiltrates on endomyocardial biopsy samples. Six of eleven patients (54%) had a striking increase in levels of anti-HLA antibodies in close temporal proximity with the episode of acute allograft dysfunction. Cardiac allograft function improved in all patients with intensification of immunosuppression. PMID- 8476885 TI - Vascular rejection in heart transplant recipients. AB - Antibody medicated (vascular) rejection has recently been described in heart transplantation. We report our experience with vascular rejection in a series of 62 patients who did not receive perioperative lymphocyte antibody therapy. Sixty five rejections were reported, of which 58 (89%) were pure cellular; five (8%) had both cellular and vascular components, and two (3%) had only vascular rejection. Vascular rejection was very common in patients in whom hemodynamic compromise developed, and hemodynamic compromise was significantly more common in vascular than cellular rejection. Treatment for vascular rejection included plasmapheresis, intravenous methylprednisolone, and cyclophosphamide. Only one death occurred in this series, and that occurred in a patient with vascular rejection where the diagnosis and initiation of therapy were delayed. The role of vascular rejection in patients with hemodynamic compromise is discussed. PMID- 8476886 TI - Patients who die awaiting heart transplantation. AB - In the United States, heart donor availability has increasingly failed to keep pace with rising demand. Transplant data were obtained from the United Network for Organ Sharing for 1988, 1989, and 1990 and by survey of 50 heart transplantation centers, which performed 1932 transplantations between 1983 and 1989. According to the United Network for Organ Sharing, 512 patients on the waiting list died in 1988; 527, in 1989; 650, in 1990, and if present trends continue more than 800 will have died in 1991. Similar numbers of patients were inactivated or removed from the list each year. Only 49% of patients (1647 of 3390) on the heart transplant waiting list at some time in 1988 underwent the procedure in that year. For 1989 the figure fell to 42% (1630 of 3915 patients). Survey data revealed a threefold increase in the ratio of the number of patients who died/number of patients who underwent transplantation from 0.07 in 1983 to 0.21 in 1989 and in the ratio (number of patients who died+number of patients who were removed from the list)/number of patients who underwent transplantation from 0.12 in 1983 to 0.38 in 1989. The major causes of death among waiting patients were congestive heart failure (46%) and arrhythmia (29%). From 1983 to 1989, 55% (134 of 243) of those patients with documented urgency status died in the intensive care unit; 45% (109 of 243) died elsewhere. Waiting time for patients dying in the intensive care unit rose from 10.7 days in 1985 to 50.3 days in 1989; patients dying out of the intensive care unit waited 103.7 days in 1985 and 85.6 days in 1989. In conclusion, the number and proportion of potential recipients who die awaiting heart transplantation is increasing every year. Congestive heart failure and arrhythmia are the major causes of death, and similar numbers of patients die in and out of the intensive care unit. PMID- 8476887 TI - Prostaglandin E1-induced moderation of elevated pulmonary vascular resistance. Survival on waiting list and results of orthotopic heart transplantation. AB - Forty-three consecutive patients who were being treated with digitalis, angiotensin converting enzyme inhibitors, and diuretics were evaluated for orthotopic heart transplantation. After right heart catheterization in patients with more than 3 Wood units or with a mean pulmonary artery pressure higher than 30 mm Hg (n = 13; group 1), prostaglandin E1 (PGE1) therapy was initiated at a dosage of 5 ng/kg/min and was increased stepwise (mean maintenance dosage, 35 ng/kg/min) until side effects (joint pain, digital edema) occurred. After 6 days of PGE1 administration, dosage decreased stepwise. One week after PGE1 was stopped, right heart recatheterization was performed, and the patients were listed on the waiting list. Hemodynamic data significantly improved in PGE1 treated patients. Patients without pulmonary hypertension (group 2, n = 30) were put directly on the waiting list. No oversized or local donor was required for transplantation. Eight of 13 patients in group 1 underwent transplantation. The other five patients died while on the waiting list. In group 2, 15 patients underwent transplantation, and 15 patients died while on the waiting list. A prolonged mean survival time on the waiting list (6.0 versus 3.1 months, p < 0.005) was noticed in group 1. PGE1 was administered after orthotopic heart transplantation whenever indicated; no death was related to right ventricular failure in group 1. The results after orthotopic heart transplantation in patients treated with PGE1 were comparable to the control group. PGE1 therapy enabled us to perform orthotopic heart transplantation on patients with pulmonary hypertension at a comparable risk with normal heart transplant recipients. PMID- 8476888 TI - Pulmonary vasodilation after heart transplantation. A comparison among prostacyclin, sodium nitroprusside, and nitroglycerin on right ventricular function and pulmonary selectivity. AB - The aim of this study was to compare the effects of prostacyclin on central hemodynamics and right ventricular function to the more widely used vasodilators, sodium nitroprusside and nitroglycerin, and to investigate whether prostacyclin is more selective to the pulmonary vascular bed compared to sodium nitroprusside and nitroglycerin in patients after heart transplantation. Hemodynamic measurements were made after the operation in the intensive care unit with a pulmonary artery fast-response ejection fraction/volumetric thermodilution catheter. The aim was to maintain mean arterial pressure around 70 mm Hg with each drug. After a 10-minute infusion of each drug at a stable infusion rate, central hemodynamic variables and right ventricular end-diastolic volume, end systolic volume, and ejection fraction were measured or derived in triplicate. The average infusion rates of sodium nitroprusside, nitroglycerin, and prostacyclin were 3.3 +/- 1.7 micrograms/kg/min, 6.6 +/- 1.8 micrograms/kg/min, and 12.4 +/- 1.7 ng/kg/min, respectively. Cardiac output, stroke volume, right ventricular end-diastolic volume, and central filling pressures were highest for prostacyclin compared to both nitroglycerin and sodium nitroprusside. Pulmonary vascular resistance was lower for prostacyclin compared to nitroglycerin but was comparable to that of sodium nitroprusside. Systemic vascular resistance was lowest for prostacyclin compared to both sodium nitroprusside and nitroglycerin. The pulmonary vascular resistance/systemic vascular resistance ratio used as an index of pulmonary selectivity did not differ between the vasodilators. The right ventricular ejection fraction did not differ among the three drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476889 TI - Utilization of pediatric donors salvaged by cardiopulmonary resuscitation. AB - The efficacy of using infant donors with an extended cardiopulmonary resuscitation (CPR) history was investigated. Eight heart transplantations with donors who had no or minimal (less than 10 minutes) history of CPR (group A) and seven heart transplantations with donors with extended CPR history (35 to 125 minutes; mean, 59 minutes; group B) were compared for peak myosin levels after transplantation, and systolic and diastolic cardiac function in the first week after transplantation. All donor hearts had normal hemodynamics in the early postoperative period. No significant differences were found between the groups with regard to age of donors, age of recipients, donor heart ischemic time, and cardiac function in the first week after transplantation. In group B, peak myosin levels were 1.4, 4.6, 7.0, 11.3, 14.8, 20.2, and 21.3 ng/ml. These values were significantly (p < 0.05) higher than those in group A but represented only minimal myocardial damage when compared with the values in previous myocardial infarction studies. Although donors with a history of protracted CPR had higher efflux of myosin light chains perioperatively, hemodynamic recovery suggests that use of pediatric donor heart grafts after prolonged CPR is safe and efficacious. PMID- 8476890 TI - Reliable noninvasive rejection diagnosis after heart transplantation in childhood. AB - Rejection diagnosis was exclusively handled with noninvasive techniques in 16 children (mean age, 8.6 +/- 5.7 years; range, 0.9 to 15.2 years) over a total follow-up period of 18.3 patient years. No endomyocardial biopsies were performed. Intramyocardial electrogram recordings and echocardiographic investigations were used as two noninvasive techniques for rejection diagnosis. Daily noninvasive telemetric monitoring of the overnight intramyocardial electrogram was the major diagnostic guideline. The intramyocardial electrogram signal of the sleeping child was transmitted to a bedside receiver by an implanted telemetric pacemaker. The QRS amplitude was automatically analyzed and transferred to the in-hospital computer via a telephone modem connection. Rejection was diagnosed when QRS amplitude fell more than 8% below average baseline levels for 3 successive days, which was the indication for hospital admission. Medical antirejection treatment was instituted only if echocardiography showed impaired early diastolic left ventricular relaxation concomitant with a QRS-amplitude loss. The echocardiographic criterion was a prolongation of the parameter Te (Te is defined as the time span between onset of diastole and peak relaxation velocity of left ventricular wall) by more than 10 milliseconds compared to previous intraindividual values. Survival after a mean follow-up time of 13.7 months (range, 2 to 57 months) is 100%. A total of 22 rejection episodes were treated. During the first 6 postoperative months, the incidence of rejection requiring treatment was 1.4 episodes per patient. In patients at home, distant monitoring detected 13 episodes of a significant QRS amplitude drop, which led to hospital readmission. In eight children, echocardiography was likewise positive, and rejection treatment was instituted. One child with positive intramyocardial electrography received antirejection treatment because of clinical evidence of rejection, although echocardiography was negative. In three instances, systemic infection was associated with the QRS voltage loss. In one child a reason for QRS-complex reduction could not be identified. One rejection episode was treated on the grounds of clinical signs and positive echocardiography without a significant QRS-voltage drop. We conclude that distant noninvasive rejection monitoring based on meticulous application of the techniques described is a safe procedure. Daily monitoring of QRS amplitude in patients at home is an excellent safeguard against overlooking significant rejection episodes. This is of special importance in infants and children, in whom routine endomyocardial biopsy cannot be performed. Distant overnight monitoring minimizes psychosocial disturbance during follow-up after heart transplantation. PMID- 8476891 TI - Is cyclosporine toxic to the heart? AB - Cardiotoxicity caused by cyclosporine was studied in experimental rats by the uptake of radiopharmaceuticals (technetium 99m-labeled pyrophosphate and indium 111-labeled antimyosin) and histologic examination of heart tissues. A dose of 50 mg/kg (body weight) of cyclosporine and an equal volume of vehicle (cremophor-EL) were injected into the rats subcutaneously for 7 or 11 consecutive days. A statistically significant difference (p < 0.05) was noted between the uptake of the radiopharmaceuticals in the hearts of cyclosporine-treated rats compared to the control rats. For 99mTc pyrophosphate, the cardiac uptake ratios of cyclosporine-treated rats to control rats were 2.13 and 4.08 for 7-day and 11-day treatment periods, respectively. For 111In antimyosin, the ratios were greater than 2 for both 7-day and 11-day treatment periods. Histologically, vacuoles were found in single or focal groups of myocytes with interstitial edema in the hearts of cyclosporine-treated rats compared to the control rats. The results of both the uptake of the radiopharmaceuticals and the histologic evidence indicate cell injury in the hearts of cyclosporine-treated rats. Cyclosporine therefore seems to be toxic to the heart tissue. PMID- 8476892 TI - Does short-course induction with OKT3 improve outcome after heart transplantation? A randomized trial. AB - OKT3 is often used routinely for induction immunotherapy or selectively to avoid acute cyclosporine nephrotoxicity in heart transplant recipients at high risk for immediate postoperative kidney failure. It has not been shown in a randomized trial to be useful in patients at low risk for early kidney failure. We randomized 30 patients with a serum creatinine level of less than 1.4 mg/dl before heart transplantation to be treated with triple-drug immunotherapy with cyclosporine, which was started before surgery, (group 1) or to be treated with OKT3 for 4 to 6 days after surgery with oral cyclosporine, which was started between days 2 and 4, after renal function had stabilized (group 2). Follow-up for 6 months revealed no significant differences in the total number of rejection episodes, total number of infections, or in the serum creatinine level. Four patients in group 1 and five patients in group 2 have had no rejection. OKT3 showed a trend to delay time to first rejection (p = 0.10), as has been reported for the 14-day induction course of OKT3. A short course of OKT3 induction in heart transplant recipients at low risk for immediate postoperative kidney failure prolongs the time to first rejection for most patients but does not appear to reduce the total incidence of rejection in the first 6 months after heart transplantation. PMID- 8476893 TI - Urodilatin, a new therapy to prevent kidney failure after heart transplantation. AB - Kidney failure after heart transplantation still remains a crucial problem, especially when cyclosporine is used for early postoperative immunosuppressive therapy. To preserve good renal function during immunosuppression with cyclosporine, urodilatin (CDD/ANP-95-126), the kidney-born analogue to the circulating cardiac peptide hANP (CDD/ANP-99-126), was given for the first time as a long-term, low-dose infusion in addition to the usual drug therapy immediately after heart transplantation. From November 1990 to January 1992, 47 patients (44 men and three women; mean age, 51 years) were treated by a 20 ng/kg body weight/min infusion for 96 hours after heart transplantation. Renal function and hemodynamic parameters of these patients were compared with a group of 40 patients (34 male and six female; mean age, 50 years) as controls, who underwent heart transplantation from May 1990 to November 1991. Both groups did not differ significantly with respect to age, sex, indication for heart transplantation, and preoperative renal function. With urodilatin treatment, renal function was significantly improved with lower peak plasma creatinine (1.83 +/- 0.1 versus 2.47 +/- 0.19 mg/dl; p = 0.003), lower peak serum urea (118 +/- 7 versus 178.3 +/ 10.3 mg/dl; p = 0.0036) and absence of hemodialysis (0% versus 10%; p = 0.026). Additionally, adequate diuresis was maintained although furosemide was reduced by more than 50% (p = 0.005) on each day of urodilatin treatment. Mean central venous pressure was significantly lower (-2 mm Hg; p = 0.02) during application of urodilatin, despite reduction of vasodilator therapy with nitroglycerin by about 50% (p = 0.02). Because of the significantly improved renal function and beneficial hemodynamic effects, the recommendation is therefore to introduce urodilatin in the postoperative treatment protocol after heart transplantation. PMID- 8476894 TI - Vascular lesions in biopsy specimens devoid of cellular infiltrates: qualitative and quantitative immunocytochemical studies of human cardiac allografts. AB - Biopsy specimens from 80 cardiac allografts were studied immunocytochemically with nine antibodies selected to identify cellular, immunologic, and vascular aspects of rejection. Results from these experiments were converted to a numeric base and used to calculate rejection indexes for each of these aspects of rejection. Pretransplantation biopsy specimens of donor hearts were studied to determine normal values, and clinical, catheterization, and conventional biopsy findings were used to classify patients as stable or unstable. The standard deviation of cellular and immunologic reaction indexes were overlapping for stable and unstable patients, but the vascular indexes for these patient groups were significantly different, suggesting that vascular damage defines clinical instability in cardiac allograft recipients. To study the vascular index in the absence of cellular infiltrates, biopsy specimens from 80 allografted hearts were selected to represent 40 patients with cellular infiltrates and 40 patients devoid of infiltrates. The results of this analysis revealed no difference in the vascular index between hearts that contained or did not contain infiltrates; the spectrum of vascular damage between the groups ranged from trivial to severe, suggesting that vascular damage was not dependent on cellular infiltrates. Concluding that these were independent events was not possible, however, because none of the hearts continuously were devoid of cellular infiltrates. Two groups of patients with significantly different vascular indexes then were studied for a systemic manifestation of coagulation by measurement of their thrombin times. The group with low vascular index was found to have significantly prolonged thrombin times compared to the group with high vascular index, and a trend to less prolongation of thrombin times was observed in another group with high cellular index. The relation of these results with cardiac allograft vasculopathy is not established, but the results suggest hitherto unexplored roles for quantitative expressions of hemostasis, fibrinolysis, and anticoagulation in the pathophysiology of vascular disease in allografts. PMID- 8476895 TI - Identification of a subpopulation of reactive large granular mononuclear cells in allogeneic heart transplantation. AB - This study is designed to test the hypothesis that specific morphologic attributes of peripheral blood mononuclear cells, measurable by flow cytometry, are correlated with the timing and the intensity of allograft injury during the development of heart rejection. A pig model of major histocompatibility complex mismatched heterotopic heart transplantation with (n = 5) and without (n = 5) cyclosporine administration was monitored serially be telemetered electrocardiography and endomyocardial biopsies. Flow cytometric analysis of peripheral blood mononuclear cells revealed the emergence of a discrete subpopulation of peripheral blood mononuclear cells (7.8% +/- 1.0% and 8.5% +/- 0.9% before transplantation to 16.5% +/- 1.3% and 19.4% +/- 3.0% after transplantation in the untreated and the cyclosporine-treated groups, respectively, p < 0.05), exhibiting characteristic changes in forward and 90 degree light scatter, indicative of increased cell size and granularity, and possibly representing monocytes or large granular lymphocytes. Lymphocyte cell surface-marker studies indicated that 62% of these cells are DH59B+ (monocyte/granulocyte). Because intracellular free calcium is an important second messenger in lymphocyte activation we measured intracellular free calcium by flow cytometry using fluo-3. This subpopulation of cells was found to have similar intracellular free calcium when compared to normal-sized lymphocytes (104 +/- 7 nmol/L versus 101 +/- 5 nmol/L, respectively). We conclude that this lymphocyte subset detected by flow cytometry represents specifically reactive cells that are associated with incipient allograft rejection. PMID- 8476896 TI - Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System. AB - Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading systems have evolved. Most recently, the International Grading System was introduced in The Journal of Heart and Lung Transplantation. In this study the interobserver reproducibility of both the Stanford Classification and the International Grading System is evaluated using Kappa statistics. Three observers evaluated 168 endomyocardial biopsy specimens according to the Stanford Classification and 100 endomyocardial biopsy specimens according to the International Grading System. The evaluation was carried out blindly. Kappa values of 54.1% and 51.5%, respectively, were obtained, both significantly above zero but not optimal. In addition to the interobserver reproducibility analysis of the two grading systems, the International Grading System is discussed. In the original description of the grading system terms such as focal, multifocal, and aggressive infiltrates and myocyte damage and myocyte necrosis are used. These terms create some difficulties in understanding or interpreting the various grades. The main problem is to distinguish between grade 1A and grade 3A. Despite the difficulties, the grading system is easy to use, but a revision is needed. PMID- 8476897 TI - Gastrointestinal complications and endoscopic findings in heart transplant patients. AB - To determine the scope of gastrointestinal complications in heart transplant recipients, we examined the frequency and nature of gastrointestinal complications by reviewing the indications and findings of endoscopic and surgical procedures involving the gastrointestinal tract in 159 patients. All patients were treated with prednisone, azathioprine, and cyclosporine after transplantation. Sixty-seven patients (42%) had gastrointestinal symptoms significant enough to warrant either endoscopic, radiologic, or surgical procedures. Forty-seven patients (30%) underwent esophagogastroduodenoscopy or upper gastrointestinal roentgenography with a high frequency of esophagitis, gastritis, duodenitis, and gastroduodenal ulcers. Thirty-two patients (20%) underwent barium enema or endoscopic procedures of the lower gastrointestinal tract, with the most frequent findings being benign polyps and colitis. Opportunistic infections, especially with cytomegalovirus, were frequent and were only diagnosed by endoscopic procedures, indicating an advantage of endoscopy over barium studies in these patients. Twenty-three patients (15%) underwent surgical procedures for gastrointestinal complications with 2.5% mortality. Hence, significant gastrointestinal complications that are common in heart transplant recipients, can be safely managed surgically when surgical intervention is indicated. PMID- 8476898 TI - Ophthalmic complications after heart transplantation. AB - To ascertain the ophthalmic complications after heart transplantation, the authors reviewed 59 patients who had been referred to the ophthalmology department during a 4-year period and were subsequently followed for at least 1 year. Twenty-five patients (43%) were found to have lens changes in one or both eyes, which is typical of prolonged oral corticosteroid therapy. In three patients (5.2%) posterior subcapsular cataract formation progressed to a level where cataract surgery was required. In two patients (3.4%) cytomegalovirus retinitis developed within 6 months of the transplantation, and significant irreversible visual loss occurred. Retinal vascular changes were found in 22 patients (37.3%), including 18 patients with hypertensive retinopathy and one patient with background diabetic retinopathy. During the period of observation, a central retinal vein occlusion developed in one patient, an anterior ischemic optic neuropathy developed in one patient, and bilateral occipital lobe infarctions developed in one patient. Older patients and those with a longer survival time after transplantation were more likely to have ophthalmic complications (p = 0.04). Although these results indicate a low incidence of sight-threatening complications after heart transplantation, early referral of patients with visual symptoms is important. Those involved with the care of heart transplant patients should be aware of ocular complications secondary to immune suppression and underlying cardiovascular disease. PMID- 8476899 TI - Thromboxane A2 mediates reperfusion injury after heart preservation. AB - To assess the role of the eicosanoid thromboxane A2, a potent vasoconstrictor and platelet activator, in reperfusion injury after heart preservation, donor rats (n = 18) were anesthetized, and their hearts were rapidly excised, arrested with cardioplegic solution, and fitted with a left ventricular balloon. Seven hearts were subjected to 45 minutes of ischemia at 15 degrees C, simulating implantation, (group 1) during which the carotid and jugular vessels of support rats were cannulated for ex vivo blood reperfusion. Remaining hearts were preserved in 4 degrees C saline solution for 3 hours followed by 45 minutes at 15 degrees C (group 2, n = 11). Before reperfusion of group 2 hearts, support rats received either vehicle (group 2a, n = 6) or thromboxane A2 receptor antagonist SQ29548 (0.2 mg/kg) (group 2b, n = 5). After 1 hour of reperfusion, left ventricular peak-systolic pressure and end-diastolic pressure were measured in all hearts at incremental ventricular volumes. The slope of the peak-systolic pressure-volume relation and the volume-axis intercept of the end-diastolic pressure-volume relation were also measured. No significant differences were noted in mean peak-systolic pressure, at any left ventricular volume, nor slope of the peak-systolic pressure-volume relation between groups, indicating that neither preservation nor SQ29548 treatment affected systolic contractile performance in this model. Through all left ventricular volume, however, end diastolic pressure was significantly lower (p < 0.05) in group 2b compared to group 2a, and overall did not differ significantly from group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476900 TI - Functional recovery in rabbit heart after preservation with a blood cardioplegic solution and perfusion. AB - Thirty-five isolated rabbit hearts were subjected to 60 minutes of storage after cardiac arrest with high K+ crystalloid cardioplegic solution at 5 degrees C. They were divided into five groups (n = 7 per group) according to the preservative protocol: group I (simple immersion in 0 degrees C normal saline solution), group II (simple immersion in 30 degrees C blood cardioplegic solution), group III (immersion and perfusion in 30 degrees C blood cardioplegic solution), group IV (simple immersion in 10 degrees C blood cardioplegic solution), and group V (immersion and perfusion in 10 degrees C blood cardioplegic solution). After storage for 1 hour, cardiac function, tissue water content, and the number of hearts capable of ejecting against a 100 cm H2O column afterload were recorded and compared among the five groups. Cardiac function in group II was not different from group I. Aortic pulse pressure and left ventricular developed pressure were lower in group II than in group III, IV, or V. Aortic developed pressure was higher in groups III and V (p < 0.05). Tissue water content in group I was significantly higher than in groups II, III, and V (p < 0.05). All hearts in groups III and V could eject against a 100 cm H2O afterload after preservation (p < 0.05 versus groups I, II, and IV). Factorial analysis among the groups using blood cardioplegic solution showed that either hypothermia or perfusion alone or the combination was a protective factor in providing functional recovery of stored hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476902 TI - Activation of the alternative pathway of complement in hyperacute xenograft rejection of rabbit hearts by human blood. AB - Isolated rabbit hearts were perfused as autoperfusing working preparations with human blood to simulate discordant hyperacute xenograft rejection. Perfusion with unmodified human blood resulted in immediate thrombotic failure of the hearts. This process was initiated by immunoglobulin M heterophile human anti-rabbit antibody, mediated by the classic pathway of complement and platelet-activating factor, and effected by platelets. Prevention of this process resulted in organ damage by another process occurring at about 20 minutes. Removal of heterophile antibody from the perfusing blood had no effect on this second event, but specific inactivation of the alternative pathway of complement prevented its generation despite normal titers of antibody and normal classic pathway activity. Studies of the deposition of components of the human complement system on the endothelium of the xenoperfused hearts confirm a role for the alternative pathway of complement in xenograft rejection in this discordant species combination. PMID- 8476901 TI - Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart. AB - Traditionally, detection of heart rejection after heart transplantation is based on histologic grading of endomyocardial biopsy specimens. The value of magnetic resonance spectroscopy for determining heart rejection was assessed in rejecting and nonrejecting isografts and allografts using energy-rich phosphate spectroscopy. In 46 rats a heterotopic abdominal heart transplantation was performed, and animals were divided into the following groups: six isografts (no rejection), five untreated allografts (severe rejection), and 35 immunosuppressed allografts (mild to moderate rejection). One week after transplantation magnetic resonance spectroscopy was performed, and data were correlated to histologic findings (rejection grades according to Stanford and the New International Working Formulation classifications and relative volume of viable myocardium). Magnetic resonance spectroscopy allows detection of moderate to severe rejection with significant alterations in the energy-rich phosphates such as a decrease in the ratio of phosphocreatine/inorganic phosphate, phosphomonoester/inorganic phosphate, and beta-adenosine triphosphate/inorganic phosphate. A significant correlation was found between spectroscopic changes (phosphocreatine/inorganic phosphate) and histologic rejection (correlation coefficient r = 0.47, p < 0.005) and/or the amount of relative volume of viable myocardium and phosphocreatine/inorganic phosphate (r = 0.58) or beta-adenosine triphosphate/inorganic phosphate (r = 0.63), respectively. In conclusion magnetic resonance spectroscopy permits detection of moderate to severe degrees of heart rejection with a sensitivity of 85% and a specificity of 61%. Changes in the energy-rich phosphates correlate with the histologic grading of heart rejection and the relative volume of viable myocardium. Magnetic resonance spectroscopy appeared to be a valid technique for detecting myocardial rejection after heart transplantation in the reported experimental model. PMID- 8476903 TI - Single lung transplantation for cystic fibrosis: is it an option? Cystic Fibrosis Transplant Study Group. AB - A 15-year-old girl with end-stage lung disease from cystic fibrosis underwent a bilateral lung transplantation. Infarction of the left lung allograft required its removal on day 10. The patient went on to have an uneventful recovery except for a prolonged air leak from the right allograft of approximately 29 days. The left pleural cavity opacified with time with no clinical or radiologic evidence of empyema. The patient was discharged on day 35 in good condition. On a follow up examination 6 months after transplantation, she appeared to be functioning extremely well with a single lung allograft. This case report challenges the conventional wisdom that bilateral pneumonectomy and single lung transplantation are not an option to be considered for patients with cystic fibrosis or bronchiectasis. PMID- 8476904 TI - The role of transbronchial biopsies in the management of lung transplant recipients. AB - We examined the utility of the transbronchial biopsy in the management of 53 lung transplant patients. One hundred thirty-three protocol biopsies were performed to ascertain the frequency and nature of abnormalities in clinically stable or asymptomatic patients; 128 diagnostic biopsies were performed in clinically ill patients to assess the morphologic abnormalities before the institution of therapy, and 105 biopsies were performed to assess the response to therapy. Histologic evidence of acute rejection was found in 24% of the protocol biopsies, and infection was found in 17%. Twenty-five patients with grade 1 or grade 2 perivascular infiltrates in protocol biopsies did not receive antirejection therapy. Follow-up biopsy in these patients showed spontaneous resolution of the infiltrates in 19% and increased infiltrates in 6. Only two of these patients became clinically ill, representing "progression" to clinical rejection in only 8% of the nontreated patients. Forty percent of the biopsies performed to rule out acute rejection or infection had histologic features of acute rejection, and another 23% had features of infection. Treatment of patients with clinical and histologic evidence of rejection was associated with rapid resolution of clinical symptoms in nearly 90% of the patients, but follow-up biopsies showed residual infiltrates compatible with ongoing or resolving rejection in 52%. Despite repeat antirejection therapy in some patients, these infiltrates persisted for an average of 30 days after the diagnostic biopsy. Follow-up biopsies also showed asymptomatic infection, usually cytomegalovirus pneumonitis, which often persisted for weeks despite the lack of symptoms. Perivascular infiltrates compatible with acute rejection were also found in 38% of biopsy specimens with evidence of infection. These perivascular infiltrates resolved with antibiotic treatment alone in nearly 50% of the patients with these features. Although perivascular mononuclear cell infiltrates are the cardinal histologic feature of acute rejection, similar infiltrates occur in patients who apparently have infection alone and other patients who have both infection and rejection; infiltrates compatible with minimal, mild, and moderate acute rejection also occur in clinically asymptomatic patients. These histologic findings are a challenge to both the pathologists' and the clinicians' skills in the management of the lung transplant patient. PMID- 8476905 TI - Monocrotaline-induced pulmonary vascular disease after contralateral lung transplantation in the rat. AB - To test a hypothesis that reduction in pulmonary perfusion pressure and flow affect underlying vascular disease, pulmonary pathology was studied in monocrotaline-treated rats undergoing single lung transplantation. Inbred rats were treated with 40 mg/kg (group T1, n = 6) and 80 mg/kg of monocrotaline (group T2, n = 9), received a left lung isograft 2 and 4 weeks after medication, and were killed 4 and 6 weeks after single lung transplantation, respectively. For each group, rats receiving the same amount of monocrotaline (M1, M2) or vehicle (N1, N2) served as controls. Monocrotaline-treated rats developed pulmonary vascular disease and right heart failure, resulting in severe exercise intolerance in M1 or death in M2 unless single lung transplantation had been carried out. At death, pulmonary blood flow was directed toward the left lung isograft, and the retained right lung received a significantly reduced fraction of cardiac output. Right to left ventricular weight ratio was significantly reduced in both groups as compared to the respective control rats, suggesting reduced perfusion pressure. Although thickness of media in small pulmonary arteries (media/radius) was normal (34% +/- 4%) in the lung isografts, it was significantly increased in the contralateral lung (group T1, 45% +/- 5%; group T2, 48% +/- 3%), which was not significantly different from that of monocrotaline treated control rats, respectively (group M1, 47% +/- 7%; group M2, 49% +/- 6%). Although single lung transplantation reduced perfusion pressure and flow toward the monocrotaline-treated native lung, it failed to affect vascular morphology significantly. PMID- 8476906 TI - Surgical management of infective endocarditis after heart-lung transplantation. AB - Bacterial endocarditis after heart-lung transplantation has not been described. We report Staphylococcus aureus bacterial endocarditis in a 12-year-old boy after heart-lung transplantation. He was found to have an apparently free vegetation in his left ventricle, which was surgically removed. After a stormy postoperative period, he successfully recovered and remains well after 6 months. PMID- 8476907 TI - Serum cytokine levels in heart allograft recipients: correlation with findings on endomyocardial biopsy. AB - The ability to detect rejection of human cardiac allografts depends on endomyocardial biopsy diagnosis. Because cytokines are known to mediate allograft rejection events, we chose to examine serum levels of specific cytokines and receptors (interleukin-2 [IL-2], IL-2 receptor [IL-2R], and tumor necrosis factor alpha [TNF-alpha]) and to correlate those levels with findings on endomyocardial biopsy. Sequential sera samples from 23 cardiac allograft recipients were examined for the cytokine levels mentioned, and data correlated with findings on endomyocardial biopsy. Briefly, no statistically correlation of serum cytokine or receptor levels with the stage of allograft rejection was found. When sequential serum cytokine levels were determined in patients experiencing humoral and cellular allograft rejection events, the levels of TNF-alpha appeared to correlate well with endomyocardial biopsy findings. IL-2 and IL-2R levels in two patients who never experienced rejection were elevated on occasion, but TNF-alpha levels were always negative. In summary, measurement of serum cytokine (IL-2, IL 2R) levels in cardiac allograft recipients does not appear to correlate with findings on endomyocardial biopsy; however, elevated levels of TNF-alpha appear to predict more severe humoral allograft rejection episodes and may be helpful in this regard. PMID- 8476908 TI - Monitoring rejection in infants after heart transplantation. PMID- 8476909 TI - Two-year follow-up of a heart transplant patient being treated with cyclosporine and ketoconazole. PMID- 8476910 TI - Effect of oxidant exposure on monkey intestinal brush-border membrane. AB - This study looks at the effect of oxidant exposure on changes in structural components and functional properties of monkey intestinal brush-border membrane vesicles (BBMV). These membranes were found resistant to iron-dependent lipid peroxidation as judged by measurement of various parameters such as formation of malonaldehyde (MDA) and conjugated diene and depletion of total arachidonic acid, tocopherol and membrane-associated protein thiol groups. Free radicals generated by thermal decomposition of 2,2'-azobis(2-amidinopropane) dihydrochloride (ABAP) which does not require iron, were capable of inducing lipid peroxidation in this membrane. Fluorescence polarisation studies used to assess the physical state of the membrane lipids after exposure to various free radical generating systems showed that ABAP could decrease the fluidity of BBMV whereas other systems had no effect. Exposure of BBMV to ABAP or cumene hydroperoxide decreased the glucose and amino acid transport. BBMV had a high content of nonesterified fatty acids as part of the total lipids and removal of these free fatty acids by treatment with fatty acid free albumin made the membranes susceptible to iron-dependent peroxidation. These studies suggest that intestinal epithelial cell membranes are resistant to iron-dependent lipid peroxidation due to the presence of membrane associated free fatty acids. Possibly lipid peroxidation may play a less significant role in damage to these cells. PMID- 8476911 TI - Annexin I interactions with human neutrophil specific granules: fusogenicity and coaggregation with plasma membrane vesicles. AB - The interactions of annexin I with specific granules isolated from human neutrophils were investigated. Unfractionated cytosol induced Ca(2+)-dependent granule self-aggregation and fusion of granules with model phospholipid vesicles. High Ca2+ concentrations were required for these processes (500-600 microM for the half-maximal rate of granule self-aggregation; 100-200 microM for the half maximal rate of fusion with phospholipid vesicles). These activities were inhibited by a monoclonal antibody specific for annexin I and immunodepletion of cytosol by this antibody greatly reduced activity, implicating annexin I as the major mediator of these processes in neutrophil cytosol. The fact that the Ca2+ concentration dependences differed for different membranes suggests that specificity may be controlled by the type of intracellular membrane involved and the local Ca2+ concentration. Trypsin treatment of granules enhanced the rate of fusion of phospholipid vesicles with granules, suggesting that access to phospholipids in the granule membrane may be modulated by granule proteins or that a fusogenic protein factor in the granule membrane is activated by trypsin treatment. Coaggregation of specific granules with plasma membrane vesicles mediated by Ca2+ and annexin I was suggested by the fact that granules preincubated with Ca2+, cytosol and plasma membrane vesicles blocked the fusion of subsequently added phospholipid vesicles with the plasma membrane vesicles. These data suggest a role for annexin I as part of a multiprotein system involved in membrane-membrane contact necessary for exocytosis of specific granules in human neutrophils. PMID- 8476912 TI - Coupling of ligands to liposomes independently of solute entrapment: observations on the formed vesicles. AB - Bovine serum albumin (BSA), employed as a model ligand, was covalently linked (about 16% of the amount used) to small unilamellar vesicles (SUV) composed of phospholipid, cholesterol and N-(p-aminophenyl)stearylamide (APSA) (molar ratios 1:1:0.05). SUV with bound BSA were then used to generate dehydration-rehydration vesicles (DRV) in the presence of tetanus toxoid and/or carboxyfluorescein (CF). Nearly all of the SUV-bound BSA (about 15% of the original amount) was recovered in the multilamellar DRV formed, with a considerable proportion (42-62%) of the ligand becoming available on the outer bilayers. This apparent spatial reorientation of BSA within DRV also caused the entrapped toxoid to shift to some extent to the liposomal surface. There was no significant difference in the z average mean size between DRV with and without coupled BSA (543 and 555 nm diameter, respectively). Percent number diameter distribution data revealed that 71.2 (BSA-free) and 76.4% (BSA-containing DRV) of the vesicles had diameters of about 300-440 and 330-420 nm, respectively. However, in terms of percent mass diameter distribution, 69.5% (BSA-free) and 65.2% (BSA-containing DRV) of the mass was in vesicles with corresponding ranges of diameter of 1381-2975 and 1086 2840 nm. Vesicle size heterogeneity in both preparations was confirmed by freeze fracture electron microscopy which also indicated that structures with or without bound BSA, were mostly vesicular of the multilamellar type. Judging from CF latency values, ligand-bearing DRV were stable on incubation with blood plasma at 37 degrees C for 24 h. Stability was, however, reduced significantly when the amount of ligand bound was excessive. The present approach allows for the coupling of ligands to and the entrapment of antigens and other labile solutes in liposomes independently, thus avoiding potential damage of such solutes by the coupling reagents. PMID- 8476914 TI - Uptake and transport of fluorescent derivatives of dolichol in human fibroblasts. AB - We are using fluorescent derivatives to visualize the endocytic transport of dolichol intermediates from the cell surface to the lysosome, and to estimate their rate of turnover within the lysosome. Anthroyl dolichol and anthroyl [1 14C]dolichol were synthesized and purified by chromatography on silica and C18 Sep-Paks followed by high-performance liquid chromatography on C18. The successful synthesis of anthroyl polyisoprenoid alcohols was confirmed by the use of uv-visible spectrometry and by fluorescence spectrometry. The purified esters were taken up into Ham's media containing 10-30% fetal calf serum or alternatively reconstituted into phospholipid liposomes for delivery to human fibroblasts in culture. The uptake of fluorescent dolichol esters into the cells and into lysosomes was demonstrated using fluorescence microscopy. The localization of anthroyl dolichol in lysosomes was further documented by simultaneously labeling fibroblasts with anthroyl dolichol and FITC-dextran a recognized lysosomal marker. Fibroblasts generally showed several groupings (domains) of lysosomes, some were dually labeled while others were labeled exclusively with either anthroyl dolichol or FITC-dextran. Labeling with anthroyl dolichol was very slow relative to labeling of the same fibroblasts with FITC dextran suggesting that anthroyl dolichol acts as a labeling agent for intracellular membranes, particularly those of the lysosome while the dextran fluorescence is presumably of lysosolic origin. Several types of experiments were done with anthroyl [1-14C]dolichol to establish that the fluorescence seen in lysosomes represents anthroyl dolichol. Anthroyl dolichol appears to enter fibroblasts intact, since we were unable to recover any free [1-14C]dolichol from total lipid extracts of (i) media used for the uptake of anthroyl dolichol or (ii) the media removed from cells labelled for 42 h. In addition, attempts to hydrolyze anthroyl [1-14C]dolichol in vitro using whole fibroblast homogenates at pH 4.0 and 7.5 were unsuccessful, even though the fibroblasts expressed acid lipase activity using 4-methylumbelliferyl palmitate as substrate. PMID- 8476913 TI - Function of intracellular [Ca2+]i in exocytosis and transbilayer movement in human platelets surface-labeled with the fluorescent probe 1-(4 trimethylammonio)phenyl)-6-phenyl-1,3,5-hexatriene. AB - Ellipsometry indicated that 1-(4-(trimethylammonio)phenyl-6-phenylhexa-1,3,5 triene (TMA-DPH) bound to platelets in a reversible and saturable way. Accordingly, the fluorescence intensity (F) of a suspension of TMA-DPH-labeled platelets was described as a quantity, determined by the amount of TMA-DPH bound to the platelet surface. Most platelet activators elevated F to a degree that correlate well with the secretion of serotonin evoked by these activators. The increase in F levels reflected the increase in outer membrane surface area following exocytosis. However, activators that evoked prolonged (> 2.5 min) and strong (> 600 nM) elevations of cytosolic [Ca2+]i increased F to levels that were much higher than expected from the maximal increase in surface area due to exocytosis. This high increase in F was caused by inward transbilayer movement of TMA-DPH over the plasma membrane and the subsequent labeling of cytosolic membrane sides. The kinetics of exocytosis and changes in cytosolic [Ca2+]i were studied by stopped-flow mixing of platelets with agonist. Thrombin-induced exocytosis had a delay of only 3 s, which was shortened when external CaCl2 or ADP was present. This correlated well with a faster rise in [Ca2+]i in the presence of CaCl2 or ADP, indicating that exocytosis was linked in time to elevation of [Ca2+]i. By itself, ADP was unable to evoke exocytosis and it elicited a [Ca2+]i transient of much shorter duration than thrombin, but with similar maximum. We concluded that both exocytosis and transbilayer movement were associated with elevation of [Ca2+]i: exocytosis required a moderate, relatively prolonged rise and transbilayer movement was accompanied by a stronger rise of even longer duration. Influx of external Ca2+ was essential for transbilayer movement, but not for exocytosis. PMID- 8476915 TI - Na(+)-dependent and -independent uridine uptake in an established renal epithelial cell line, OK, from the opossum kidney. AB - The characteristics of Na(+)-dependent and Na(+)-independent uridine uptake at 22 degrees C were determined for monolayers of OK renal epithelial cells. The majority of uridine influx in subconfluent to early confluent (day 1 postconfluency) OK monolayers was mediated via a facilitated-diffusion pathway (apparent Km 160 +/- 41 microM, Vmax 610 +/- 100 pmol/mg protein per min). This system was inhibited with high affinity by nitrobenzylthioinosine (NBMPR) (IC50 value 1.5 nM) and by purine and pyrimidine nucleosides. Specific [3H]NBMPR binding sites were detected in OK monolayers (apparent Kd 0.67 +/- 0.25 nM, Bmax 90 +/- 19 fmol/mg protein) yielding a turnover number for the carrier of 112 uridine molecules/site per s at 22 degrees C. Na(+)-dependent uridine uptake was minor in subconfluent OK monolayers, but increased 8-fold with time after confluency reaching a stable plateau at 8 days postconfluency. Inhibition of Na(+)-dependent 1 microM uridine uptake by inosine, guanosine, adenosine and uridine was biphasic with approx. 40% of the total uptake inhibited with high affinity (IC50 value 2 to 14 microM). Concentrations of thymidine and cytidine up to 1 mM had no effect on Na(+)-dependent uridine uptake and no Na(+)-dependent thymidine influx by confluent OK monolayers was detected. Using cell monolayers grown on a permeable filter support, Na(+)-dependent uridine uptake occurred preferentially from the apical surface. This high affinity component of Na(+) dependent uridine uptake is suggested to represent the Na(+)-dependent purine preferring N1 nucleoside transporter. The Na+/uridine stoichiometry for this system was consistent with 1:1. The remaining component of Na(+)-dependent uridine uptake was inhibited by some nucleosides, such as guanosine and inosine, with low affinity (IC50 values of 0.6 to 5 mM). Other nucleosides showed little specific inhibition. We propose that this component of uridine uptake represents a mutated carrier that binds nucleosides but is defective in the translocation of permeant. PMID- 8476916 TI - Human immunodeficiency virus type 1 (HIV-1) fusion with model membranes: kinetic analysis and the role of lipid composition, pH and divalent cations. AB - The kinetics and extent of HIV-1 fusion with model membranes was studied. HIV-1 was labeled with octadecyl rhodamine B chloride, and fusion was monitored continuously as the dilution of the probe into target membranes. The results were analyzed by a mass action model which yielded good simulations and predictions for the kinetics and final extents of fluorescence increase. The model determined the percent of virions capable of fusing and rate constants of fusion, aggregation and dissociation. Ultrastructural analysis of the virus and reaction products by electron microscopy also provided evidence of HIV-1 fusion with membranes lacking CD4. HIV-1 fusion activity depends on the target membrane lipid composition according to the sequence: cardiolipin (CL) > > phosphatidylinositol > CL/dioleoylphosphatidylcholine (DOPC) (3:7), phosphatidic acid > phosphatidylserine (PS), PS/cholesterol (2:1) > PS/PC (1:1), PS/phosphatidylethanolamine (1:1) > DOPC, erythrocyte ghosts. Reduction of pH from 7.5 generally enhances the rate and extent of HIV-1 fusion. Physiologically relevant concentrations of calcium stimulate HIV-1 fusion with several liposome compositions and with erythrocyte ghost membranes. The fusion products of HIV-1 with liposomes consist of a single virus and several liposomes. The mass action analysis revealed that, compared to intact virions, the fusion products show a striking reduction in the fusion rate constant. Like influenza and Sendai viruses, HIV-1 fusion with membranes containing its own envelope glycoprotein(s) is strongly inhibited. Unlike these viruses, HIV-1 fusion is promoted by physiological levels of calcium. HIV-1 fusion with liposomes is qualitatively similar to simian immunodeficiency virus fusion. PMID- 8476917 TI - The effect of positive and negative pH-gradients on the stability of small unilamellar vesicles of negatively charged phospholipids. AB - The stability of small unilamellar vesicles (SUV) made from negatively-charged phosphatidate by ultrasonication or pH-jump has been investigated. As criteria for the vesicle stability are used: (I) the bilayer integrity as judged from the permeability of the fluorescent probe carboxyfluorescein (CF) and (II) the susceptibility of the phospholipid vesicles to fusion as judged by gel filtration and freeze-fracture electron microscopy. Egg phosphatidate SUV (PA-SUV) whose internal cavity is in equilibrium with the dispersion medium are strictly speaking thermodynamically unstable by these criteria. They may, however, be regarded as stable from a practical point of view. CF-release is observed with a half-time of 14 days and also some vesicle fusion, particularly at low temperature (4 degrees C). The small effects observed, e.g., the small tendency of the vesicles to undergo fusion is probably due to the high surface charge density of PA bilayers. A main finding of this work is that the same positive pH gradient which is used in the pH-jump method to drive the formation of SUV from large phosphatidic acid bilayer sheets has a stabilizing effect on the resulting PA-SUV. Stabilization is achieved by positive pH-gradients of about two pH-units or more with the pH of the external medium exceeding the pH of the vesicle cavity. Under these conditions, up to about 8 weeks no significant loss of entrapped CF and no fusion of SUV was observed both at 4 degrees C and room temperature. In contrast, a reverse or negative pH-gradient of several pH units applied to PA-SUV (with the external pH being lower than that of the vesicle cavity) destabilizes PA-SUV. Such a gradient can be shown to lead to a dramatic perturbation of the lipid bilayer packing as evident from a significant increase in CF permeability. The local perturbation of the phospholipid bilayer is accompanied by massive vesicle fusion which is prominent at low temperature (4 degrees C). PMID- 8476918 TI - Membrane heterogeneity in isolated rat hepatocytes and liver plasma membrane subfractions: a comparative study using DPH and its cationic derivative TMA-DPH. AB - The fluorescence decay of 1,6-diphenyl-1,3,5-hexatriene (DPH) and of 1-(4 trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) has been studied in hepatocytes isolated from rat liver and in isolated plasma membrane subfractions (cLPM, canalicular membranes and bLPM, basolateral membranes) using frequency domain fluorometry. The decay has been analyzed either by using a model of discrete exponential components or a model that assumes a continuous distribution of lifetime values in order to study different aspects of membrane heterogeneity. The results obtained by the two analyses are practically superimposable but the distributional approach allows an evaluation of membrane heterogeneity through the width of the distribution that has shown particularly significant differences when freshly hepatocytes are compared with in vitro aged hepatocytes. Moreover, the comparison of the distributional analysis of the two probes has shown in cLPM a tendency to higher values of the main lifetime component and a narrower distribution width with respect to bLPM. These results indicate changes of membrane domain organization that have been discussed in relation with the specific lipid composition that characterizes the two membrane subfractions. Our results indicate that frequency domain fluorometry may be used to study membrane heterogeneity in intact cells and isolated membranes. PMID- 8476919 TI - Targeting and delivery of bactericide to adsorbed oral bacteria by use of proteoliposomes. AB - Proteoliposomes having surface-bound succinylated concanavalin A (s-conA) have been prepared from a range of phospholipid mixtures by sonication (SUV) and reverse phase evaporation (REV) covering a range of size (weight-average diameter (dw)) from approx. 35 to 310 nm and weight-average number of protein molecules per liposomes (Pw) from approx. 50 to 3000. The targeting of the proteoliposomes to adsorbed biofilms of the bacteria Streptococcus sanguis and Streptococcus mutans has been assessed from the extent of inhibition of an enzyme-linked immunosorbent assay (ELISA) for bacterial cell surface antigens. The surface bound lectin enhances targeting relative to 'naked' liposomes of comparable concentration by factors of 2-50 depending on the liposomal lipid composition and Pw. The effect of the bactericide Triclosan on the thermal properties and permeability characteristics of liposomes has been studied. At and above a molar ratio of Triclosan to lipid of 0.6, Triclosan eliminates the gel to liquid crystalline phase transition in dipalmitoylphosphatidylcholine (DPPC) containing liposomes and increases the bilayer permeability of both liposomes and proteoliposomes to D-glucose. The proteoliposomes have been used to deliver Triclosan to S. sanguis biofilms and the inhibition of growth of the bacteria after treatment with liposomally delivered Triclosan has been determined using a microtitre plate re-growth assay and compared with growth inhibition by 'free' Triclosan. It is shown that for short exposure times (1 to 2 min) proteoliposomally delivered Triclosan is a more effective growth inhibitor than free Triclosan. The results are discussed in terms of the targeting, retention and subsequent release of Triclosan into the bacterial biofilms. PMID- 8476920 TI - Membrane potential determination in large unilamellar vesicles with hexakis(2 methoxyisobutylisonitrile)technetium(I). AB - The accumulation of the lipophilic cation hexakis (2 methoxyisobutylisonitrile)technetium (99mTc-MIBI) within large unilamellar vesicles made from egg phosphatidylcholine was examined as a function of time and membrane potential (Em). Equilibrium distribution occurred within minutes at 30 degrees C. The transmembrane distribution of Tc-MIBI was measured at Em = 0 mV and at a series of negative membrane potentials. The distribution of Tc-MIBI was in close agreement with the Nernst equation for passive distribution of a permeant ion across a bilayer, permitting the membrane potential to be predicted from Tc-MIBI distribution. In this respect, Tc-MIBI behaves similarly to other radioprobes of membrane potential, but with unique properties including high specific activity (10(9) Ci/mol), rapid kinetics of distribution, low potential independent binding, and short half-life (6.02 h). The results indicate a mechanism for tissue accumulation of Tc-MIBI in vivo that may in part account for its utility in clinical imaging of ischemic myocardium. PMID- 8476921 TI - Baclofen (beta-p-chlorophenyl-gamma-aminobutyric acid) transport across rat jejunum. AB - Intestinal transport of baclofen (beta-(p-chlorophenyl)-gamma-aminobutyric acid) in the rat has been examined in vitro. Influx of baclofen across the brush-border membrane (JmcBacl) and steady-state accumulation by everted segments of the intestine were measured. JmcBacl could be accounted for as the sum of a saturable process with a maximum rate of approx. 10-20 nmol cm-2 h-1 and a K1/2Bacl of approx. 0.3 mM and a diffusive contribution with a permeability of 0.073 cm h-1. JmcBacl was Na(+)- and Cl(-)-independent. The steady state distribution ratio between the intracellular space of the everted segments and incubation fluid was 1.0 +/- 0.1 (n = 12). Inhibition tests demonstrated that the Na(+)- and Cl(-) independent, passive, but saturable fraction of baclofen transport can not be mediated by any of the known amino acid carriers of the rat small intestine. Preliminary results suggests that qualitatively baclofen transport in guinea-pig and rabbit is also by facilitated transport. PMID- 8476922 TI - Mesophase formation by ceramides and cholesterol: a model for stratum corneum lipid packing? AB - Previous X-ray diffraction and electron microscopy experiments have suggested that there is an unusual double bilayer structure formed by stratum corneum lipids, with a lamellar spacing of about 131 A (White, S.H., Mirejovsky, D. and King, G.I. (1988) Biochemistry 27, 3725-3732; Hou, S.Y.E., Mitra, A.K., White, S.H., Menon, G.K., Ghadially, R. and Elias, P.M. (1991) J. Invest. Dermatol. 96, 215-223; Bouwstra, J.A., De Vries, M.A., Gouris, G.S., Bras, W., Brussee, J. and Ponec, M. (1991) J. Controlled Release 15, 209-220). Two contradictory models have been proposed for this structure. In the Downing model, used to explain electron microscopy observations, acylceramides are vital, acting as a 'lynch pin' and holding the lipid layers together (Swartzendruber, W.C., Kitko, D.J., Madison, K.C. and Downing, D.T. (1989) J. Invest. Dermatol. 92, 251-257). Alternatively, to explain X-ray diffraction results from intact corneum, protein intercallation into the lipid bilayers is suggested, since an electron dense region wider than can be accounted for by lipid headgroups alone, is required (Bouwstra, J.A., De Vries, M.A., Gouris, G.S., Bras, W., Brussee, J. and Ponec, M. (1991) J. Controlled Release 15, 209-220). Thus, existing models require the presence of either acylceramides or protein. We describe how a similar structure can be prepared in vitro using mixtures of cholesterol and ceramides. Cholesterol induces a novel double-bilayer structure in ceramides II, and IV. This result is in conflict with the existing literature which cites acylceramides, or protein as instrumental in maintaining the in vivo structure of the phase. Characterisation has been carried out using optical microscopy and synchrotron X-ray diffraction. PMID- 8476923 TI - Functional analysis of the promoters of the human CaMIII calmodulin gene and of the intronless gene coding for a calmodulin-like protein. AB - More than 1 kb of the 5'-flanking DNA of the human CaMIII calmodulin gene and of the calmodulin-like protein (CLP) gene have been sequenced. Notable features are the absence of a TATA-box and the presence of AGGGA elements in both upstream regions, the presence of several sequences with homology to known regulatory elements (cAMP-, retinoic acid- and interferon-responsive elements) in the CLP gene, and a high G + C-content and several putative Sp1-factor-binding sites in the CaMIII gene. 1 kb of the CaMIII upstream region was driving high-level growth hormone (hGH) reporter gene expression in human teratoma and monkey COS cells. Promoter activity dropped to about 30% and 10% when only 252 bp and 114 bp, respectively, of the CaMIII sequence were present. In contrast to the CaMIII promoter, the CLP gene upstream region was driving hGH expression only in human teratoma, but not in monkey COS cells. Addition of retinoic acid to the transfected cells had minimal effects on both promoters, leading to a 10-30% decrease of activity. The results show that the human CaMIII gene contains a strong and ubiquitously active promoter, whereas the promoter of the intronless CLP gene appears to be regulated in a cell-specific manner. PMID- 8476924 TI - Effects of N-terminal truncations upon chloroplast NADP-malate dehydrogenases from pea and spinach. AB - Using the purification procedure of Fickenscher and Scheibe (Biochim. Biophys. Acta 749 (1983), 249-254) and a modification of the method, we produced a series of NADP-MDH forms from spinach and pea-leaf extracts that were characterized by a stepwise shortening of the N-terminal sequences. Limited proteolysis of the enzymes resulted in the generation of even shorter forms. Immunoprecipitation of the NADP-MDH from crude extracts revealed that the sequences of the intact enzymes from pea, spinach and maize started at a position (Ser) identical with that established for the Sorghum enzyme (Cretin, C., et al. (1990) Eur. J. Biochem. 192, 299-303). Spinach NADP-MDH isolated by conventional methods was shown to represent the intact form. Thus, the kinetic, regulatory and structural properties of the various truncated forms could be compared with those of an intact form. Removal of 5 or 11 amino acids, as occurred during isolation of the pea NADP-MDH, was without any significant effect. The enzymes were all dimeric and still exhibited the characteristic redox-regulatory properties. However, removal of 31 and 37 amino acids using aminopeptidase K resulted in the formation of active monomers characterized by only slightly lowered affinities towards the substrates, a shift of their pH optimum from 8 to 7, the loss of oxaloacetate inhibition and an increased maximal velocity. Although these forms lacked most or all of the N-terminal extra-peptide, including the 2 cysteines involved in redox modification, they were still sensitive to the redox-potential. However, the low concentration of thiol required for immediate and complete restoration of any lost activity (40 mM beta-mercaptoethanol) suggested that this reaction might not be relevant for redox-regulation in vivo. PMID- 8476925 TI - Activation of the hydroxylase of sMMO from Methylococcus capsulatus (Bath) by hydrogen peroxide. AB - Hydrogen peroxide can activate the non-heme binuclear iron-containing hydroxylase of soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath) in the catalysis of oxidation of methane and other sMMO substrates. The reductase, protein B, O2 and NADH are normally required for catalytic activity, but can be replaced by H2O2 serving as the source of both oxygen and electrons for the reaction. Similar results have been observed in a different strain of MMO from Methylosinus trichosporium OB3b (Andersson, K.K., Froland, W.A., Lee, S.-K. and Lipscomb, J.D. (1991) New J. Chem. 15, 410-415). The Km,app for H2O2 was found to be 66 mM. Labelled oxygen experiments show that the oxygen atom in the product in the peroxide driven system is derived from H2O2 and not O2. Using C2-C5 alkanes and 2-butene as substrates it was shown that the product distribution differed in the complete sMMO and H2O2-driven systems, indicating that more than one pathway is available to the enzyme. Protein B, which is required for catalytic activity in the complete system, was found to be an inhibitor of the hydroxylase/H2O2 system. It was also observed that protein B not only affected the activity, but also the selectivity of carbon hydroxylation with 2-methylbutane as substrate. PMID- 8476926 TI - Kinetic studies on the reactions of separated a, b and c subunits of Panulirus interruptus deoxy-hemocyanin with hydrogen peroxide. AB - The kinetics of the H2O2 oxidation of separated a, b and c subunits (75 kDa, 657 amino acids) of the arthropod Panulirus interruptus hemocyanin (Hc), in the deoxy Cu(I)2 state, have been studied at 25 degrees C, I = 0.100 M (NaCl). Solutions of oxyHc provide small equilibrium amounts of the deoxy reactant deoxyHc + O2<- >oxyHc (K approx. 10(5) M-1). The reaction is of interest because H2O2 is one of the few molecules which is able to access the active site and oxidise deoxyHc to the metHc Cu(II)2 state. The reaction was studied at pH values in the range 6.8 9.6. Traces of Ca2+ (and other 2+ ions) are controlled by addition of EDTA (5 mM). With or without EDTA hexamer forms are present at the lower pH values. At pH > 8.3 and with EDTA added, a and b (3% sequence difference) give monomer forms. The hexamers are however retained at the higher pH values if Ca2+ (10 mM) is added. As in the corresponding studies of deoxyHc with O2, rate constants for subunit c (42% sequence differences) show no variation with pH and the hexamer is retained over the whole pH-range explored. Rate constants for the reactions of H2O2 with the different monomer and hexamer deoxyHc forms of a, b, and c are in the range 1-75 M-1 s-1. A mild pseudo-catalase activity of metHc leading to reformation of oxyHc also contributes to the reaction. PMID- 8476927 TI - Tyrosinatable and non-tyrosinatable tubulin subpopulations in rat muscle in comparison with those in brain. AB - Using immunobinding and enzymatic assays we determined in rat muscle extracts the proportion of tyrosinatable tubulin, that is, tubulin that participates in the tyrosination/detyrosination cycle. We found that in muscle, in contrast with nervous tissue, practically all tubulin molecules are tyrosinatable. In the case of rat brain the non-tyrosinatable tubulin pool accounts for about 50% of the tubulin. In addition, isolectrofocusing of 14C-tyrosinated tubulin from brain and muscle extracts revealed a different composition in tyrosinatable tubulin isotypes. One of the isotypes, which in muscle accounts for 86% of the 14C tyrosinated tubulin species, was detyrosinated by the action of tubulin carboxypeptidase faster than the rest of the 14C-tyrosinated tubulin isotypes taken in whole. In the case of brain extract, that isotype accounts for only 16% of the labeled tubulin. PMID- 8476928 TI - Expression in Escherichia coli of the 36 kDa domain of poly(ADP-ribose) polymerase and investigation of its DNA binding properties. AB - We have expressed in Escherichia coli the 36 kDa domain of the human poly(ADP ribose) polymerase. This polypeptide comprises the C-terminal part of the DNA binding domain, as well as the automodification region of the enzyme, but lacks the zinc-finger motifs of the N-terminal region and the C-terminal catalytic domain. By probing the crude E. coli protein extracts with radioactive DNA probes (South-Western blots), we have shown that the 36 kDa domain binds a DNA probe of 222 bp but does not bind a shorter probe of 66 bp. This interaction is stronger when the polypeptide is fused to the 55 kDa catalytic domain of the enzyme. PMID- 8476929 TI - Comparison of several new chromogenic galactosides as substrates for various beta D-galactosidases. AB - The kinetic characteristics of beta-galactosidases from bovine liver and testes, Escherichia coli, Aspergillus niger and Jack bean were studied using five newly developed colorimetric substrates. All the chromophores released by enzyme hydrolysis had high extinction coefficients in the visible region of the spectrum. Varying amounts of substrate inhibition were found with each of these substrates (VBzTM-Gal, VLM-Gal, VLPr-Gal, VQM-Gal and VQPr-Gal), but this was not a significant problem if the correct assay conditions were used. The substrates attached particularly tightly to the active centre of E. coli beta-D galactosidase resulting in low Km values. The data suggest that the chemical properties of the heterocyclic portion of the aglycone distant from the glycosidic oxygen do not affect the substrate specificity and the substrate inhibition can be attributed to interactions not involving the catalytic site. When the product of the maximum observed velocity (Vm) and the molar absorption coefficient is calculated for each substrate, the relative merits of the substrates for the assay of each enzyme can be assessed. The beta-D galactosidases from fungal and bacterial sources hydrolysed the substrates most efficiently, indicating that they may be of particular value in areas of molecular biology and biotechnology. PMID- 8476930 TI - Oxidized and Met358-->Leu mutated alpha 1-proteinase inhibitor as substrates of Pseudomonas aeruginosa elastase. AB - This paper investigates the catalytic activity of Pseudomonas aeruginosa elastase using the bait region of the alpha 1-proteinase inhibitor as a substrate. The bacterial enzyme cleaves the Pro357-Met358 bond of the wild-type inhibitor and the recombinant Met358 inhibitor and the Pro357-Leu358 bond of the recombinant Met358-->Leu inhibitor with kcat/Km values of 9 x 10(4) M-1 s-1, 1.4 x 10(5) M-1 s-1 and 3.5 x 10(5) M-1 s-1, respectively. In contrast, the N-chlorosuccinimide oxidized inhibitor (Met351 and Met358 = methionine sulfoxides) is cleaved at the Glu354-Ala355 position with a significantly lower rate (kcat/Km = 10(4) M-1 s-1). The pH optimum for the cleavage of the native, the oxidized, the Met358-->Leu mutated inhibitor, and 2-aminobenzoyl-Ala-Gly-Leu-Ala-4-nitrobenzylamide, a synthetic Pseudomonas elastase substrate are, 6.0, 7.0, 6.5 and 5.8, respectively. We conclude that P. aeruginosa elastase readily hydrolyzes substrates with P'1 methionine or alanine residues and that its pH optimum is not as alkaline as usually thought. PMID- 8476931 TI - Ligand affinities in mutant metmyoglobins. AB - Ligand binding to the wild-type and a series of mutant porcine myoglobins, expressed and purified from Escherichia coli cells, has been studied using UV-VIS absorption spectroscopy. The proximal pocket mutation, F7 Ser-->Leu (F7), causes an increased affinity for OH- and N3- binding to metmyoglobin. A hydrogen bond between the F7 serine residue and the imidazole side-chain of the proximal histidine has been removed by this mutation. It is suggested that this allows the imidazole group to reorientate, reducing the steric clash between itself and the haem pyrrole nitrogen atoms and leading to a shortening of the bond between the proximal histidine and the haem iron. Other conformational changes further away from the haem pocket have also been induced, but the mutant still crystallizes under the same conditions as for the wild-type protein. A series of distal pocket mutants, E11 Val-->Thr (VT), E7 His-->Val (HV) and a mutant with both of these substitutions (M2) all have greatly reduced the OH- and N3- binding affinity. These effects have been interpreted by considering several factors: the changed stability of the aquometmyoglobin form, hydrogen-bond formation between the ligand and the E7 residue, and electrostatic repulsion between the ligand and the E11 threonine residue. PMID- 8476932 TI - Characterization of yeast EF-1 alpha: non-conservation of post-translational modifications. AB - Elongation factor 1 alpha (EF-1 alpha) is an abundant cellular protein and its amino-acid sequence has been inferred from numerous organisms, including bacteria, archaebacteria, plants and animals. In large measure, it would appear that the overall structure has probably been maintained given the 33% identity and 56% similarity of Escherichia coli EF-Tu with human EF-1 alpha. Chemical sequencing of EF-Tu and EF-1 alpha has revealed that these proteins are post translationally modified. In order to assess the possible function of these modifications, we have chemically sequenced the EF-1 alpha from the lower eukaryote Saccharomyces cerevisiae (yeast). To our surprise, the methylation pattern of yeast EF-1 alpha was quite different from either rabbit or brine shrimp EF-1 alpha with only the trimethyllysine at position 79 conserved although the yeast protein is 81% identical to rabbit EF-1 alpha. A dimethyllysine was observed at position 316 which corresponds to a trimethyllysine in brine shrimp and rabbit EF-1 alpha. The other positions in yeast EF-1 alpha which were methylated were unrelated to the other six possible positions for modification observed in brine shrimp or rabbit EF-1 alpha. In addition, the unique glyceryl phosphorylethanolamine observed in mammalian EF-1 alpha and suspected in brine shrimp EF-1 alpha was not found in yeast EF-1 alpha. PMID- 8476933 TI - Molecular dynamics study of the stability of staphylococcal nuclease mutants: component analysis of the free energy difference of denaturation. AB - The stability of two mutants G88V (Gly-88-->Val) and A69T (Ala-69-->Thr) of staphylococcal nuclease was analyzed by molecular dynamics simulations. The calculated free energy differences of denaturation for G88V and A69T were -1.1 and -2.8 kcal/mol, respectively. These values are in good agreement with the experimental values. The free energy differences divided into electrostatic and van der Waals components were analyzed. These two mutants are mainly destabilized due to van der Waals interactions. There is little difference between the electrostatic contribution to the free energy change in the native state and that in the denatured state. In each mutant structure, a small cavity appears in the vicinity of the perturbed residue. It is suggested that intramolecular van der Waals interactions of the mutants are weaker than those of the wild-type. Furthermore, analyses of the contributions of each residue near the perturbed residue and of water to the free energy difference of denaturation suggest that the interaction between water and the perturbed residue plays a very important role in the stability of staphylococcal nuclease, and that a small hydrophobic core consisting of the three aromatic rings (Tyr-27, Phe-34, Phe-76) and the side chain of Met-32 is also important for the stability. PMID- 8476934 TI - Renaturation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides after denaturation in 4 M guanidine hydrochloride: kinetics of aggregation and reactivation. AB - In 4 M guanidine hydrochloride (GdnHCl), the dimeric enzyme glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides (G6PD) dissociated to subunits and was extensively unfolded. Rapid dilution of this high GdnHCl concentration allowed G6PD to partially renature, as measured by enzyme reactivation, to a level which depended on the conditions employed. The fraction of the enzyme which did not renature aggregated and precipitated out of solution, a process which could not be substantially prevented by stabilizing additives. Based on the enzyme concentration dependence of the reactivation yield and on a comparison of the aggregation and reactivation rates, it was determined that aggregation and reactivation compete kinetically for a partially-folded intermediate only very early in the process, during the rapid GdnHCl-dilution step. The kinetics of G6PD reactivation were sigmoidal, indicating that this process involves more than one rate-limiting reaction. The kinetics depended on enzyme concentration in a higher than first-order manner, indicating that association of subunits is one of the rate-limiting reactions. A renaturation mechanism compatible with these observations is described, which involves a bi-unimolecular (subunit association folding) reaction sequence, with rate constants equal to 2.19 microM-1 min-1 and 0.140 min-1, respectively. This mechanism involves an inactive, dimeric, G6PD folding intermediate, a species whose existence has recently been established by equilibrium denaturation experiments (Plomer, J.J. and Gafni, A. (1992) Biochim. Biophys. Acta 1122, 234-242). PMID- 8476935 TI - Immunologic evidence for three isoforms of AMP deaminase (AMPD) in mature skeletal muscle. AB - Four rabbit polyclonal antisera to purified AMP deaminase (AMPD) isozymes were used to precipitate homogenate AMPD activity from dissected gracilis, soleus and gastrocnemius muscles of the cat, rabbit, rat, mouse, Rhesus monkey, human and toad. The antisera were also tested against other unusual muscles: autonomically innervated striated muscle of the upper esophagus (UEM), skeletal muscle of patients with myo-AMPD deficiency and extraocular muscles (EOM) of humans and Rhesus monkeys. The reference antiserum, M, prepared against human psoas muscle AMPD, precipitated > 90% AMPD from all primate skeletal muscles tested, and from type-2 muscles of all mammals tested, but < 75% from cat and rodent soleus, toad gastrocnemius and primate UEM, EOM and myo-AMPD deficient muscles. Thus, a second isozyme was clearly indicated. Antibody B, against rat liver and kidney AMPD, had no effect with any muscle specimen. Antibody C, against rat heart AMPD, produced additive precipitation of AMPD from soleus of rat and mouse, while antibody E1, against human red cell (and heart) AMPD, produced additive AMPD precipitation from toad gastrocnemius, cat soleus and muscles of several AMPD-deficient humans. A second AMPD isozyme thus accounted for as much as 25% of total activity in some animal red muscles, but no more than 5% in human mixed muscles. At least one more isozyme is needed to account for muscle AMPD unreactive with all antibodies tested in rabbit soleus, toad gastrocnemius and primate UEM and EOM. A list is appended of the approximate AMPD activity in various human cells and tissues. PMID- 8476936 TI - Perspectives on linkage of primary health care and substance abuse treatment. PMID- 8476937 TI - Current pharmacotherapies for cocaine abuse: a review. AB - This article attempts to summarize the results of clinical trials on various pharmacotherapies for cocaine abuse described in the literature. A wide variety of drugs have been used for cocaine abuse. They include drugs for the treatment of coexisting psychiatric disorders, cocaine antagonists, dopamimetic agents, L dopa/carbidopa, the amino acids tyrosine and tryptophan, antidepressants, anticonvulsants, and antabuse-like drugs. Emphasis is placed throughout this review on how extensively each drug has been tested, how successful each drug has proven to be in treating cocaine abuse, and on which drugs require further investigation. PMID- 8476938 TI - 1990-1991 survey of pharmacotherapies used in the treatment of cocaine abuse. AB - In order to assess the usefulness of pharmacotherapeutic agents in cocaine treatment, all 3,631 physician members of the American Society of Addiction Medicine (ASAM) were surveyed. Five hundred and two physicians indicated use of pharmacotherapies, involving treatment experiences with approximately 79,760 patients for cocaine detoxification, and with 37,166 patients for cocaine abstinence maintenance. For both detoxification and abstinence maintenance, the four most commonly prescribed medications were amantadine, bromocriptine, desipramine, and l-tryptophan. As expected, these four medications were also the preferred treatment by a majority of physicians expressing any preference. Some relatively new medications are also being tried for the treatment of cocaine abuse, specifically carbamazepine, fluoxetine, and Tropamine. PMID- 8476940 TI - Public policy statement on the role of Medical Review Officers. PMID- 8476939 TI - General medical care and the addictions. PMID- 8476941 TI - Public policy statement, on addiction medicine and health insurance reform. PMID- 8476942 TI - Laboratory tests for rapid screening of drugs of abuse in the workplace: a review. AB - The use of rapid, on-site drug detection devices is reviewed. These tests permit the detection of various psychoactive substances in urine, and are easily used by nonskilled personnel. Saliva tests are available for detection of alcohol. These rapid tests have varying degrees of accuracy, and it is recommended that positive outcomes for all rapid tests be verified by standard laboratory procedures. The tests have potential use in the emergency room, doctor's office, drug treatment program, and the work place. When access to formal laboratory testing is limited by either time or location, an easily portable test can give critical information. A number of commercially available tests are reviewed for method, accuracy, advantages and disadvantages. Consequently, the interested practitioner should be able to find a suitable screening test from among the tests reviewed. PMID- 8476943 TI - Alcoholism in a coronary care unit population. AB - To estimate prospectively the concordance between diagnoses of alcoholism by a physician and by use of a questionnaire-type screening test in patients in a coronary care unit, we studied 608 patients admitted to a coronary care unit in a 5 1/2-month period. The results from the Self-Administered Alcoholism Screening Test (SAAST) were compared with the diagnoses by physicians recorded in the medical records for the same patients. A strong association (P < 0.001) existed between the clinicians' identification of an alcohol problem and the SAAST scores indicative of such a problem. However, 23 (4.2%) patients were identified as alcoholics by the SAAST but not by clinicians, and 16 (2.9%) patients were identified as alcoholics by clinicians but not by the SAAST. The SAAST was well accepted in this coronary care unit and can complement and extend the clinicians' impression, although each approach may identify some patients that the other will miss. Routine use of the SAAST in the coronary care unit or other hospital settings is feasible and, with appropriate clinician assessment and physician involvement, should yield more complete evaluation and case finding for alcoholism. PMID- 8476944 TI - Women at high risk of HIV infection from drug use. AB - The purpose of this project was to study women at high risk for contracting AIDS from intravenous drug use or from sexual contact with addicts. Characteristics of the population, differences between HIV+ and HIV- women, substance abuse in primary caretakers of this high risk population, and changes in drug use when learning of HIV status were investigated. Subjects were mothers at high risk for contracting HIV, whose children were referred to a pediatric AIDS clinic of a large urban hospital because of AIDS risk factors. HIV testing revealed that 27 women were HIV+ and 13 were HIV-. The most common source of infection reported by the HIV+ women was sexual contact (17 subjects), with the remainder reporting that they were unsure of the source or reported intravenous drug use as their source of infection. There were significant differences between HIV+ and HIV- mothers with regard to the presence and impact of substance abuse in their own primary caretakers before age 16. Substance abuse in the parents of subjects was apparently reflected in behaviors reflecting health risk in subsequent generations. Subjects did not report changes in AIDS risk behavior when informed of their own HIV status or that of their children. PMID- 8476945 TI - Protective and risk factors associated with drug use among Hispanic youth. AB - Analysis of data from a nationally representative sample of Hispanic youths age 12-17 and their parents was done to investigate the impact of a number of variables on youths' drug-using behavior. The significance of youth, household, and parental characteristics were tested using measures of youth drug use as dependent variables in regression models. Parents' attitudes and use of licit and illicit drugs were found to play an important role in their children's drug use behavior. The results also provide some support for the hypothesis that Hispanic children whose parents are more acculturated into American society are at higher risk of using drugs. Youths of Mexican origin, youths living outside large metropolitan areas, and females were found to be more likely to use drugs. The results provide supportive evidence that for drug prevention education programs to be effective with Hispanic youths, they must be family oriented. PMID- 8476946 TI - Barbarians at the gates. PMID- 8476947 TI - [The status of the direct magnifying x-ray technique in orthopedics]. AB - 22 patients suffering from different orthopaedic disease patterns were x-rayed with direct x-ray magnification with focus diameters between 0.012 and 0.100 mm. This yielded improved resolution of detail structures, especially in tumours and aseptic bone necroses. Due to the relatively low efficiency of the x-ray tube (conditioned by the physics of the x-ray equipment), however, exposure times of several seconds were required, and the voltage had to be higher than in conventional x-ray procedure. This resulted in lack of sharpness due to movement and to a loss in contrast. Hence, the clinical use of focus diameters below 0.1 mm does not seem to be meaningful. PMID- 8476948 TI - [CT arthrography of the shoulder joint]. AB - Double-contrast CT arthrography of the shoulder is an imaging modality of great diagnostic accuracy with regard to glenohumeral instabilities. The purpose of this study is to describe the technique of the method and to demonstrate normal and pathological conditions in detail. Finally, its diagnostic value compared to other imaging modalities is outlined. PMID- 8476949 TI - [A stress fracture following osteosarcoma in a child--differential diagnosis]. AB - 1 1/2 years following resection of an osteosarcoma of the right proximal fibula, pain and roentgenologic lesions of the right tibia at exactly the same level were first of all suspicious of tumour relapse. Analysis of the findings of conventional films revealed the diagnosis of stress fracture. PMID- 8476950 TI - [The infiltrating angiolipoma--a rare soft tissue tumor with a malignant appearance]. AB - Angiolipomas are rare benign soft tissue tumours that are mostly encapsulated by fibrous tissue. A case of an infiltrating angiolipoma with mixed vascularisation, not surrounded by a capsule, is described. Differentiation between lipoid degenerated fibromas, lipoid histiocytoses and haemangiomas is radiologically possible with an extensive security and enables an adequate choice of the surgical procedure. PMID- 8476951 TI - [An arteriovenous fistula following laminectomy--sonographic diagnosis]. AB - In a 36-year-old woman, 10 years after laminectomy, a tentative diagnosis of arteriovenous shunt between the right iliac artery and vein, a rare complication of this procedure, was made on the basis of ultrasonographic findings. The signs consisted of dilatation of the iliac vein and of the inferior vena cava, a vascular bruit and tactile fremitus in the abdomen. In addition, cardiac enlargement and slight tricuspid and mitral incompetence in the absence of cardiac insufficiency were noted. After angiographic verification of the diagnosis the anomaly was corrected surgically. PMID- 8476952 TI - [Pulmonary sequestration: use of MR-angiography]. AB - The confirmation of the diagnosis of intralobar pulmonary sequestration usually requires angiographic demonstration of the systemic arterial supply, and venous drainage. Magnetic resonance angiography (MR angiography) is a new, non-invasive imaging modality for examinations of the vasculature. In this report we describe its successful application in intralobar pulmonary sequestration demonstrating the feeding systemic artery, including its intrapulmonary branching, and the type of the venous return. PMID- 8476953 TI - [Bilateral pneumothorax, pneumomediastinum and pneumoperitoneum following unilateral percutaneous lung biopsy]. AB - Case report on a 53-year old male patient; after transthoracic resection of the oesophagus a unilateral percutaneous biopsy of a newly developed round focus of the lung led to a bilateral pneumothorax (as well as a pneumomediastinum and a pneumoperitoneum). After transthoracic surgery the described alterations have also to be taken into account as possible complications of a unilateral percutaneous lung-biopsy. PMID- 8476954 TI - [Minimal invasive surgery, maximum results]. PMID- 8476955 TI - [Injuries of the thoracic skeleton]. AB - Injuries of the thoracic skeleton are an important indicator of other, relevant traumatic changes after a polytrauma. Most fractures occur in the ribs, followed by fractures of the clavicle, the scapula and the sternum. Because of their high kinetic energy, car accidents are the main reason for thoracic fractures. The basic radiologic tool is the a.p. projection of the thorax in supine position; in addition, other conventional x-ray examinations or computed tomography are performed. Most thoracic fractures are treated conservatively, only in few cases (instability of the thorax, risk of pseudoarthrosis, incongruence of joint surfaces) surgical procedures are used. PMID- 8476956 TI - [Imaging of the normal anatomy of the hand using high resolution magnetic resonance tomography and surface coils]. AB - Magnetic resonance imaging can visualize the soft tissue and the bone marrow of the hand. High spatial resolution requires the use of a surface coil. Signal-to noise contrast was measured and compared for 3 different coils. Optimal results were obtained with a surface coil with a diameter of 8.5 cm. The wrist and the fingers of 10 volunteers each were examined. Images with a high spatial resolution and a good signal/noise contrast were obtained, enabling the delineation of small structures like Gynon's channel and the median nerve. PMID- 8476957 TI - [Clinical magnetic resonance spectroscopy: feasibility and methods using whole body tomographs]. AB - MR Spectroscopy offers the unique possibility of monitoring the metabolism of various organs non-invasively. Using examples of 1H and 31P MR spectra, experimental and commercially available techniques are presented and evaluated with regard to their potential clinical application. An example of a 1H human brain spectrum with a pathological lactate level illustrates the requirements for MRS examinations in terms of spatial and spectral resolution. STEAM, Spin-Echo, and Chemical Shift Resolved Imaging (CSI) techniques for 1H MRS are compared. In the field of 31P MRS, typical CSI spectra of the brain and liver are presented. First experimental results with a new double-oblique 3D-CSI technique for measurement of PCr/ATP ratios of different anatomical regions of the human heart are shown. The advantages of using double-resonance techniques for Nuclear Overhauser Enhancement (NOE) and decoupling are shown by the example of the phosphodiesters of the liver. The energy metabolism of skeletal muscle under exercise is resolved with 5 sec/spectrum, showing breakdown and synthesis of photocreatine (PCr) and inorganic phosphate (Pi). Appropriate instrumentation and technique are available to many clinics today; great interest now is directed towards the diagnostic value of MRS for certain indications. PMID- 8476958 TI - Factors associated with hepatitis B infection. AB - Men and women patients not previously immunized or tested, attending the Adelaide (South Australia) STD clinic from 1988-1991, were tested for hepatitis B infection, and potential risk factors detected by multiple logistic regression. Of 7055 men and 3425 women patients tested 811 (11.5%) men and 250 (7.3%) women were seropositive. Among men seropositivity was associated with being Asian (odds ratio (OR) = 14.5), being Aboriginal (OR = 2.2), homosexual behaviour (OR = 3.8), intravenous drug use (OR = 3.2) being over 24 (OR = 2.7), previous STD (OR = 1.8), being unemployed (OR = 1.3) and having sex outside the state in the past 3 months (OR = 1.3). Among women seropositivity was associated with being Asian (OR = 10.3), being Aboriginal (OR = 2.4), intravenous drug use (OR = 3.8), being over 24 (OR = 1.6) and having vaginal discharge or dysuria (OR = 1.4). Seropositivity was not independently associated with being a prostitute or having multiple sex partners in the past 3 months. Among seropositive individuals, risk factors were not readily identifiable for 15% of men and 43% of women. Univariate analysis may provide misleading indicators of risk factors because of the confounding influence of other factors, particularly intravenous drug use. In selective vaccination campaigns the target group should be determined on the basis of local circumstances. In South Australia this group should include men with an STD. The success of selective campaigns will be jeopardized by the failure to identify risk factors in many of those who become infected, and in such situations universal vaccination or widespread screening may be more appropriate strategies. PMID- 8476959 TI - Contraceptive practices in HIV seropositive females in Ireland. AB - A questionnaire was administered to a cohort of 130 HIV seropositive women attending the Department of Genitourinary Medicine, St James's Hospital, Dublin, in order to establish their current contraceptive practices. Forty (42%) of the sexually active women did not use reliable contraception; 55 (57%) used a method reliable in fertility control only, and 21 (22%) used a method reliable in terms of both partner and congenital transmission. The intravenous drug users were less likely to use reliable contraception, 9 (39%), in comparison to the heterosexual group 14 (70%), P < 0.05. The heterosexual group were more likely to use condoms consistently, 7 (35%) in comparison to one (4%) of intravenous drug users, P < 0.02. Nineteen children, 3 borne to heterosexual mothers and 16 borne to intravenous drug-using mothers were HIV seropositive after 18 months. PMID- 8476960 TI - Roxithromycin compared to doxycycline in the treatment of genital chlamydial infection and non-specific urethritis. AB - A single-blind randomized follow-up study was conducted to evaluate the efficacy and tolerance of roxithromycin 300 mg once a day compared to doxycycline 200 mg day 1 and 100 mg day 2-10 in the treatment of genital chlamydial infection in men and women and non-specific urethritis (NSU) in men. A total of 211 patients (200 men and 11 women) between 18 and 46 years were enrolled. The women were excluded from the efficacy analysis because of the low number, but were included in the tolerance analysis. The clinical (clearance of polymorphonuclear leucocytes in urethral smears) and bacteriological response was evaluated one and 11 days after the treatment. Of 113 included men with chlamydial infection, 105 (93%) and 96 (85%) were evaluable on respective follow-up visits and of 87 included men with NSU, 74 (85%) and 64 (74%) were evaluable one and 11 days after treatment, respectively. The bacteriological eradication rate immediately after the treatment in chlamydia positive patients was 92.7% and 100% for roxithromycin and doxycycline, respectively, and 91.8% and 100% at follow-up. The clinical cure rate of all evaluable patients was 83.1% and 80.7% for roxithromycin and doxycycline, respectively, one day after the treatment and 80.5% and 85.3% for the two drugs, respectively, 11 days after treatment. None of these observed differences was statistically significant. The diagnosis did not influence the clinical response rate with either drug. Probable and possible drug-related side effects were more common after doxycycline than after roxithromycin, 35% and 19% respectively (P = 0.0032).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476961 TI - Restricting personal behaviour: case studies on legal measures to prevent the spread of HIV. AB - People infected with HIV who persist in exposing others to infection through negligent, reckless, or criminal activity create a legal and ethical dilemma for public officials. Protection of the public health requires balancing the rights of infected people with the expectations of society. When reasonable efforts fail to obtain the voluntary cooperation of infected individuals, Colorado law permits health officers to restrict their behaviour. Since 1986, at least 20 people who were aware of their infection are known to have exposed others to HIV in Colorado Springs, Colorado. Restrictive measures have been initiated in 14 cases to date. Presented here is an overview of Colorado law, selected case studies, and a summary of its strengths and shortcomings. PMID- 8476963 TI - Investigation of haematospermia. PMID- 8476962 TI - Anonymized sero-survey of HIV in a genitourinary medicine clinic population. AB - An anonymized sero-survey of the prevalence of HIV antibody was performed at an inner city Genitourinary medicine clinic in Birmingham. In 1991 8686 patients undergoing routine serological syphilis tests were anonymously tested for HIV antibodies once during the year. Demographic information was recorded for each sample but they were otherwise unlinked. There were 31 samples which tested positive for anti-HIV 1 from this group compared with 13 diagnosed by concomitant voluntary named testing. Sero-prevalence rates of 0.17% for women and heterosexual men and 4.37% for homosexual/bisexual men were found. No drug users tested positive. The survey provided evidence of occult disease outside the recognized risk behaviour patterns of homosexual men and injecting drug users outside London. PMID- 8476964 TI - Is pediculosis pubis a recurrent disease in some men? PMID- 8476965 TI - Cervical neoplasia and sexually transmitted diseases among prostitutes in Oviedo, Spain. PMID- 8476966 TI - The incubation period of first episode genital herpes. PMID- 8476967 TI - Streptococci and the genital tract. AB - Streptococci of Lancefield Group B (GBS) are known to cause maternal sepsis and neonatal infection, whereas streptococci Lancefield Group A (GAS) cause vulvo vaginitis in both children and adults. Prevalence of SGB colonization of the lower genital tract of normal women is between 4-18%, with higher rates found in hospital personnel and delivery rooms. Such high carriage rates may be a significant factor in nosocomial transmission of GBS to neonates. Symptomatic infection is uncommon and usually secondary to other pathological states. Amnionitis is a complication of vaginal carriage of GBS and there is now evidence that chorioamnionitis is associated with pre-term labour and its attendant problems. GBS infection of the male genitalia has also been described. Intrapartum chemoprophylaxis has been shown to prevent early onset GBS disease of the neonate. Prevalence of GAS in the genital tract is lower than that for GBS, but is more likely to be symptomatic. The response to penicillin is usually prompt. Optimal drug regimens need to be determined, particularly for use in pregnancy. PMID- 8476968 TI - The role of aerosol pentamidine prophylaxis. AB - Pneumocystis carinii pneumonia (PCP) is the most frequent opportunistic infection in patients with AIDS, occurring in 80% and recurring in 50% of patients within 12 months of the first episode. Prophylaxis for PCP is recommended if the CD4+ cell count is < 200 x 10(6)/l or 20% of the total lymphocyte count, or after an episode of PCP. The most effective prophylactic agent currently is trimethoprim sulphamethoxazole and should be the drug of choice but alternatives such as aerosol pentamidine are being increasingly used for patients who cannot tolerate this combination or other oral preparations. If aerosol pentamidine is used and administered via a Respigard II Marquest nebulizer, the dosage should be higher than the currently recommended monthly dosage of 300 mg. PMID- 8476969 TI - A review and update on adult syphilis, with particular reference to its treatment. AB - Syphilis has become less common in Europe in the last decade, but has once again become a major problem in the USA, and remains so in many developing countries. Several treponemal genes have now been cloned and expressed in Escherichia coli, allowing study of treponemal proteins. The importance of cell mediated immunity in syphilis has been demonstrated in animal models. A diagnosis of syphilis is usually confirmed by dark-field microscopy or serological tests. Seroconversion may be delayed in HIV infected individuals. A positive reaginic test in cerebrospinal fluid (CSF) has a high specificity but low sensitivity in the diagnosis of neurosyphilis. Indeed, virulent treponemes can be identified in CSF samples which have negative reaginic tests, normal cell counts and protein levels. In the CSF, the FTA-Abs test has a high sensitivity but low specificity for neurosyphilis. Penicillin remains the treatment of choice for all stages of syphilis, although it penetrates the blood brain barrier poorly. Treatment with intramuscular benzathine penicillin 2.4 million units stat, or 600,000 units procaine penicillin daily does not produce treponemicidal levels within the CSF. However, the incidence of neurosyphilis is low in immunocompetent patients treated with such regimens during early syphilis. Acceptable alternatives in penicillin-allergic patients include ceftriaxone and doxycycline. Erythromycin is not recommended as it has produced unacceptably high rates of treatment failure. Recently, a strain of macrolide-resistant Treponema pallidum was isolated from a patient with secondary syphilis. For the treatment of neurosyphilis, treponemicidal levels of penicillin can be achieved in the CSF using 2.4 million units procaine penicillin daily with concurrent probenecid 500 mg 4 times a day, or an intravenous infusion of benzyl penicillin 12-24 million units daily. Early syphilis can be treated adequately over 10 days, but 21 to 28 days is appropriate for late syphilis. In HIV-infected patients syphilis may present atypically with initially negative serological tests. Treatment of early syphilis in HIV-positive patients has been associated with the early development of neurosyphilis. It is advisable to treat all patients co-infected with HIV with an antibiotic regimen that achieves adequate levels within the CSF. PMID- 8476970 TI - Case definitions for paediatric AIDS: the Zambian experience. AB - For the purpose of surveillance of the acquired immunodeficiency syndrome (AIDS) in developing countries, the World Health Organization (WHO) has recommended criteria for the clinical case definition of AIDS in adults and children. In a preliminary examination of children in Zambia a number of patients with obvious AIDS did not fit the published WHO case definition for paediatric AIDS. Based on this the Zambia National AIDS Surveillance Committee designed local criteria for the clinical case definition of paediatric AIDS. We compared the Zambian criteria with the WHO criteria for the diagnosis of paediatric AIDS by studying 134 consecutively admitted children to one of the paediatric wards at the University Teaching Hospital in Lusaka. Twenty-nine of the patients were HIV-1 seropositive and 105 were HIV-1 seronegative. Among the 29 HIV-seropositive patients, the Zambian criteria identified 23, and the WHO criteria identified 20 children as having AIDS. The 105 HIV-seronegative children were classified as having AIDS in 9 cases by the Zambian criteria and in 38 cases by the WHO criteria. These results give the Zambian criteria for the diagnosis of AIDS a sensitivity of 79.3%, a specificity of 91.4% and a positive predictive value of 86.8% compared to a sensitivity of 69%, specificity of 64% and a positive predictive value of 38% for the WHO criteria. The current WHO criteria are inadequate for the diagnosis of paediatric AIDS. The need to refine the WHO criteria for the diagnosis of paediatric AIDS is discussed. PMID- 8476971 TI - How often do condoms break or slip off in use? AB - Men attending 3 sexually transmissible disease clinics and a university health service in Sydney were given a questionnaire asking how many condoms they had used in the past year and how many broke during application or use or slipped off. Respondents were 544 men aged 18 to 54 years. Of these, 402 men reported using 13,691 condoms for vaginal or anal intercourse; 7.3% reportedly broke during application or use and 4.4% slipped off. Men having sex with men reported slightly higher slippage rates than those having sex with women. Breakage and slippage were unevenly distributed among the sample: a few men experienced very high failure rates. A volunteer subsample reported 3 months later on condoms supplied to them: 36 men used 529 condoms, of which 2.8% broke during application or use and 3.4% slipped off. Many of these failures pose no risk to the user, especially those occurring during application, as long as they are noticed at the time, but failure may discourage future use. Research is needed to identify user behaviours related to breakage. PMID- 8476973 TI - Determining the prevalence of neurosyphilis in a cohort co-infected with HIV. AB - A retrospective study of 767 HIV positive patients from a large urban public hospital, 238 of whom were co-infected with syphilis, was performed to determine the prevalence of neurosyphilis. A prevalence of 3% of neurosyphilis in the co infected cohort was demonstrated. The 7 cases of neurosyphilis ascertained were of the early stage variety, with cranial nerve involvement the predominant focal deficit. Of the 5 cases presenting after initial diagnosis and treatment of syphilis, 4 were felt to be inadequately treated. An overall prevalence of 1% (7/767) was determined for the entire HIV(+) cohort. The majority of the cases of syphilis (90%) were characterized as latent syphilis. Based on these findings, the authors recommend routine CSF examination in all patients who are HIV positive and who present with latent syphilis. Treatment regimens should be maximized in an effort to reduce the prevalence of neurosyphilis in such a co infected cohort. PMID- 8476972 TI - Sexual behaviour and use of the condom by men attending gay bars and clubs in Glasgow and Edinburgh. AB - How widespread are the safer forms of sexual behaviour reportedly adopted by male homosexuals in recent years? A questionnaire was completed by 173 and 83 gay men attending gay bars and clubs in Edinburgh and Glasgow respectively. Comparisons were made between those who reported using the condom (n = 137, [54%]) and those who did not (n = 119, [46%]). Sixty percent of respondents reported more than 5 partners during the previous year. Condom use was much less common among men with less than 5 years' experience as a practising homosexual. Less than one-fifth of respondents reported always using a condom during anal intercourse. Orogenital contact without a condom was reported by 84% of all respondents, and unprotected anal intercourse by 40%, (over 30% for those who used condoms). About one-third of condom users but only 14% of non-users thought they were at risk of catching HIV because of their sexual behaviour, although 80% of users and 70% of non-users said their lifestyles had been affected by the HIV epidemic. While there were some encouraging signs of behaviour change, unprotected anal sex is still widely practised. Gay bars and clubs represent important venues for conveying the safer sex message. PMID- 8476974 TI - A new method for analysis of heart rate variability: counting statistics of 1/f fluctuations. AB - 1/f fluctuations in heart rate are usually measured spectral analysis using Fast Fourier Transform. Here, we introduce a new method based on counting the number of QRS complexes in time intervals delta t of various length. For a 1/fb spectrum the variance of counts in delta t follows a power-law as delta t1+b. This method is applied to analyze long term fluctuations in heart rate variability in 10 healthy men. The results show periods of 1/f fluctuations with interpolated periods of white noise during night hours. PMID- 8476975 TI - Neural organization of the locomotive oscillator. AB - We study the relation of neural development, organization, and activity to behavior. We provide a model of the locomotive oscillator, a neural system supplying alternating stimulation to extensor and flexor muscles creating an oscillatory motion. We propose a protocol by which this neural system starting from unstructured, unconnected neural populations develops structure and function. The protocol is studied by both computer simulation and mathematical analysis. Our main results are 1. The locomotive oscillator self-organizes and maintains its organization, assuming certain properties of the neural populations. 2. Imperfections disturbing the functional adequacy of the neural populations may lead to the deterioration and disappearance of the oscillatory behavior. 3. The locomotive oscillator may fail to organize if the development is not staged in time. PMID- 8476976 TI - A neural network model for kindling of focal epilepsy: basic mechanism. AB - A simple neural network model is proposed for kindling--the phenomenon of generating epilepsy by means of repeated electrical stimulation. The model satisfies Dale's hypothesis, incorporates a Hebb-like learning rule and has low periodic activity in absence of shocks. Many of the experimental observations are reproduced and some new experiments are suggested. It is proposed that the main reason for kindling is the formation of a large number of excitatory synaptic connections due to learning. PMID- 8476977 TI - A neural model for nonassociative learning in a prototypical sensory-motor scheme: the landing reaction in flies. AB - Nonassociative learning is an important property of neural organization in both vertebrate and invertebrate species. In this paper we propose a neural model for nonassociative learning in a well studied prototypical sensory-motor scheme: the landing reaction of flies. The general structure of the model consists of sensory processing stages, a sensory-motor gate network, and motor control circuits. The paper concentrates on the sensory-motor gate network which has an agonist antagonist structure. Sensory inputs to this circuit are transduced by chemical messenger systems whose dynamics include depletion and replenishment terms. The resulting circuit is a gated dipole anatomy and we show that it gives a good account of nonassociative learning in the landing reaction of the fly. PMID- 8476978 TI - The relationship between smoothness and performance during the practice of a lower limb obstacle avoidance task. AB - The relationship between performance (movement time) and smoothness was examined as subjects (n = 8) practiced a simple lower limb obstacle avoidance task. Smoothness was quantified by endpoint 3D jerk-cost, partitioned into magnitudinal and directional components. Data were collected with two WATSMART cameras at a sampling rate of 200 Hz for three sets of two trial blocks, including trials 1, 2, 13, 14, 25, and 26. Ten practice trials were performed between blocks of recorded trials. A DLT method was used to reconstruct 3D position coordinates of the fifth metatarsal of the subject's right (dominant) foot, considered to be the endpoint. After the data were smoothed with a fourth order, zero lag Butterworth filter, the time period was normalized so that a comparison of jerk-cost could be made between trials. Very rapid decreases in both movement time and jerk-cost measures were followed by gradual decreases, indicating that the movement became smoother as performance improved. Correlation coefficients between movement time and the various components of jerk-cost ranged from 0.70 to 0.78, supporting the hypothesis that moving more smoothly enables a person to move more rapidly during an obstacle avoidance task. PMID- 8476979 TI - Oscillatory binocular system and temporal segmentation of stereoscopic depth surfaces. AB - A dynamical neural network model of binocular stereopsis is proposed to solve the problem of segmentation which remains ambiguous even when the problem of binocular correspondence is solved. Being compatible with the recent neurophysiological findings (Engel et al. 1991), the model assumes that neural cells show oscillatory activities and that segmentation into a coherent depth surface is coded by synchronization of activities. Employing appropriate constraints for segmentation, the present model shows proper segmentation of depth surfaces and also solves segmentational ambiguity caused by a gap. It is newly shown that binocularly-unmatched monocular cells are discriminated in temporal segmentation of monocular cells caused by recurrent interactions between monocular and binocular cells. Integrative interactions with the other visual components through temporal segmentation are also discussed. PMID- 8476980 TI - Rapid synchronization through fast threshold modulation. AB - Synchronization properties of locally coupled neural oscillators were investigated analytically and by computer simulation. When coupled in a manner that mimics excitatory chemical synapses, oscillators having more than one time scale (relaxation oscillators) are shown to approach synchrony using mechanisms very different from that of oscillators with a more sinusoidal waveform. The relaxation oscillators make critical use of fast modulations of their thresholds, leading to a rate of synchronization relatively independent of coupling strength within some basin of attraction; this rate is faster for oscillators that have conductance-based features than for neural caricatures such as the FitzHugh Nagumo equations that lack such features. Computer simulations of one-dimensional arrays show that oscillators in the relaxation regime synchronize much more rapidly than oscillators with the same equations whose parameters have been modulated to yield a more sinusoidal waveform. We present a heuristic explanation of this effect based on properties of the coupling mechanisms that can affect the way the synchronization scales with array length. These results suggest that the emergent synchronization behavior of oscillating neural networks can be dramatically influenced by the intrinsic properties of the network components. Possible implications for perceptual feature binding and attention are discussed. PMID- 8476981 TI - Presynaptic and postsynaptic competition in models for the development of neuromuscular connections. AB - In the establishment of connections between nerve and muscle there is an initial stage when each muscle fibre is innervated by several different motor axons. Withdrawal of connections then takes place until each fibre has contact from just a single axon. The evidence suggests that the withdrawal process involves competition between nerve terminals. We examine in formal models several types of competitive mechanism that have been proposed for this phenomenon. We show that a model which combines competition for a presynaptic resource with competition for a postsynaptic resource is superior to others. This model accounts for many anatomical and physiological findings and has a biologically plausible implementation. Intrinsic withdrawal appears to be a side effect of the competitive mechanism rather than a separate non-competitive feature. The model's capabilities are confirmed by theoretical analysis and full scale computer simulations. PMID- 8476982 TI - Constants underlying frequency changes in biological rhythmic movements. AB - When an animal increases or decreases the frequency of its limb motions, how should the transformation in timing be characterized? It has been hypothesized that the transformation is adiabatic, even though the biological conditions are nonconservative and non-rate-limited (Kugler and Turvey 1987). An adiabatic transformation requires that the rhythmic system's action (energy/frequency) and entropy production remain time-invariant throughout the transformation. The non conservative adiabatic hypothesis was evaluated through an experiment on human rhythmic hand movements. On each trial, a subject began at a prescribed frequency and then, over a 30 s interval, increased (or decreased) the frequency continuously at will. For each subject, on each increasing and decreasing trial, cycle kinetic energy was a linear function of cycle frequency with a negative energy intercept. By the adiabatic hypothesis, the slope of the function defines the constant action and the intercept defines the constant dissipation - changes in cycle frequency incur no changes in energy dissipated per cycle. Slopes and intercepts were correlated suggesting a common basis for the two constants, and the variety of cycle amplitude-cycle duration relations were in agreement with the nonmonotonic, nonlinear space-time function predicted by the hypothesis. The possibilities of addressing aspects of the data through (a) muscle modeled as a continuum of Kelvin bodies with a continuous relaxation spectrum, and (b) various classes of autonomous differential equations, were discussed. Most importantly, the discussion focused on the puzzling independence of energy cost and speed exhibited by locomoting animals differing in morphology, physiology, size, and taxa. It was suggested that the independence may reflect a very general principle - adiabatic transformability of biological movement systems. PMID- 8476983 TI - A model of the saccadic sensorimotor system of salamanders. AB - A model of the saccadic system of salamanders on the basis of electrophysiological and anatomical results is presented. The model includes centers found to be significant for the guidance of saccades in these comparatively simple vertebrates. In particular, these are the optic tectum, the bulbar reticular formation and the motor system. The latter consists of two pairs of neck-muscles, an epaxial and a hypaxial one driven by their respective motoneurons. The model includes a visual, a sensori-motor, and a motor level. At the sensory level, the retinal coordinates are transferred to the optic tectum to establish an orthogonal map of visual angles. A secondary visual map of the ipsilateral eye with a pointsymmetrical organization exists in addition. The premotor system of the tectum was modelled according to an ensemble-coding principle. Thus, local activation of the visual map results in recruitment of an appropriate number of tectal premotor units. Simulation of the model reproduces correct metric properties of salamander saccades under varying stimulus presentations. PMID- 8476984 TI - Bistability, switches and working memory in a two-neuron inhibitory-feedback model. AB - It was reported earlier that an inhibitory-feedback network inspired by neostriatal circuitry may exhibit a bistable character and spontaneous switching phenomenon within the neuronal activity. In the presence of noise and external excitation, a few local neurons switch "on" and generate streams of impulses while other neurons remain quiescent. In time, the existing "on" neurons spontaneously switch "off" and other neurons switch "on". In this paper we examine the nature of the bistability and switching phenomenon using a simple model consisting of two mutually inhibitory neurons. For nonspiking neuron model, described by a system of nonlinear differential equations, we present a simple bifurcation analysis, which follows the birth and annihilation of two stable fixed points when model parameters are varied. We show that both nonspiking and spiking models may have two stable states, but only spiking neurons exhibit switching. The mechanism of switching for model spiking neurons, described by an equivalent RC circuit with a number of currents, is analyzed using computer simulations. It is shown that switching can be described by a two-state Markov chain with one parameter, which depends on the set of model physiological parameters, such as duration of afterhyperpolarization (AHP), maximum and the time duration of inhibitory post-synaptic potentials (IPSP's) and amplitude of the neuron noise input. "On" and "off" states of the model can be rapidly changed by localized excitatory input and the network then sustains the pattern of "on" and "off" states. That is, such a network can be used as a programmable memory device.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8476985 TI - A diffusion model of a neuron and neural nets. AB - In the paper a diffusion model of a neuron is treated. A new, less restrictive than usually, condition of applicability of a diffusion model is presented. As a result the point-process-to-point-process model of a neuron is obtained, which produces an output signal of the same kind as the accepted input signals. PMID- 8476986 TI - A neural model of the dynamic activation of memory. AB - We study an Attractor Neural Network that stores natural concepts, organized in semantic classes. The concepts are represented by distributed patterns over a space of attributes, and are related by both semantic and episodic associations. While semantic relations are expressed through an hierarchical coding over the attribute space, episodic links are realized via specific synaptic projections. Due to dynamic thresholds expressing neuronal fatigue, the network's behavior is characterized by convergence toward the concept patterns on a short time scale, and by transitions between the various patterns on a longer time scale. In its baseline, undamaged state, the network manifests semantic, episodic, and random transitions, and demonstrates the phenomenon of priming. Modeling possible pathological changes, we have found that increasing the 'noise' level or the rate of neuronal fatigue decreases the frequency of semantic transitions. When neurons characterized by large synaptic connectivity are deleted, semantic transitions decay before the episodic ones, in accordance with the findings in patients with Alzheimer's disease. PMID- 8476988 TI - Cartilage mechanics and morphology, synovitis and proteoglycan fragments in rabbit joint fluid after prosthetic meniscal substitution. AB - The effects of meniscal substitution with a Dacron or Teflon prosthesis on rabbit knee-joint cartilage were studied by indentation tests, gross and histological inspection, analysis of proteoglycan fragments in joint fluid and an evaluation of synovial changes. Cartilage mechanics and cartilage morphology were similarly abnormal after meniscectomy and meniscal substitution. The elevated concentrations of proteoglycan fragments in joint fluid and the more severe synovial changes in joints with a meniscal substitute, as compared to meniscectomy, probably resulted from irritation of the artificial implant, but also reflected the remaining effects from the necessary bone drilling. In this short-term experiment, the use of an artificial meniscal substitute could not prevent cartilage degeneration after meniscectomy. PMID- 8476987 TI - Emergence of orientation selective simple cells simulated in deterministic and stochastic neural networks. AB - The processing of visual data in area 17 of the mammalian cortex is mainly performed by cells with receptive fields which are tuned to different orientations of input stimuli. The mechanisms underlying the emergence of receptive field properties of orientation selective cells are not well understood up to now. Recently, some models for the prenatal development of the receptive fields of orientation selective simple cells have been proposed, which emerge in neural networks trained by Hebb type unsupervised learning rules. These models, however, use different network architectures and are restricted to the case of identical input neurons. In this work, a biologically motivated neural network model with a general architecture is presented. It is trained with a Hebb type updating rule and with uncorrelated input. The input neurons are identified with retinal ganglion cells and exhibit mature Mexican hat type receptive fields. If the receptive fields of the input neurons have identical properties (deterministic model), a set of parameter domains is found, which characterize different kinds of receptive field maturation behaviour of the network. Results obtained by other authors with similar models are contained in this description as special cases. In addition, the more general and rarely investigated stochastic model, where random variations of the parameters describing the receptive fields of the input neurons occur, is investigated. A high sensitivity of the network against these random variations is obtained. In case of large variations of receptive field parameters of the ganglion cells, a qualitatively new kind of maturation behaviour appears. A significant part of the synaptic connections from ganglion cells to the cortical cell is removed and small simple cell receptive fields with only few lobes emerge. The stochastic model is found to provide a better description of the size, scatter and structure of receptive fields present in biological systems, than the deterministic model. PMID- 8476989 TI - TiN coating: surface characterization and haemocompatibility. AB - The left ventricular assist device under consideration is based on the principle of the Maillard-Wankel rotary pump. The construction materials must meet stringent requirements. Titanium nitride was chosen for its surface properties and graphite for its bulk characteristics. The purpose of this study was to characterize the chemical vapour deposition titanium nitride coating via morphology, roughness, crystallinity, chemical composition, to report and discuss the results of in vitro haemocompatibility tests (protein adsorption, platelet retention, haemolysis) and to discuss physico-chemical and biological results. This chemical vapour deposition titanium nitride coating is well tolerated by the blood despite its surface irregularities, and appears as a good candidate material after improvements. PMID- 8476990 TI - In vitro assessment of bacterial adhesion to Hydromer-coated cerebrospinal fluid shunts. AB - The adherence of five strains of Staphylococcus epidermidis and one strain of S. aureus to both untreated and Hydromer-coated silicone rubber cerebrospinal fluid shunts was studied in vitro using epifluorescent image analysis. All five strains of S. epidermidis showed similar levels of adherence to untreated shunts, whilst S. aureus adhered slightly better. The Hydromer coating, a hydrogel material which creates a hydrophilic layer on the shunt surface, was found to reduce bacterial adhesion levels by approximately 90% in the six strains of bacteria tested. Unfortunately, uniform coverage of the shunt surfaces (particularly internally) with Hydromer coating was not achieved during sample preparation. Bacterial adhesion levels in such areas were identical to untreated controls. This may pose problems in the in vivo use of Hydromer-coated shunts. PMID- 8476991 TI - Complement activation by polymethyl methacrylate minimized by end-point heparin attachment. AB - After intraocular lens implantation, despite good clinical results, many cataract patients develop a chronic uveitis, caused by an inflammatory response to the implant. One way to improve the biocompatibility of the intraocular lens is to modify the surface by end-point heparin attachment. This study shows that complement activation caused by poly(methyl methacrylate) can be diminished by end-point heparin attachment, as demonstrated by a significant reduction in the generation of C3a and fluid phase terminal complement complexes. It suggests that assessment of complement activation is a good indicator of the biocompatibility of intraocular lenses. PMID- 8476992 TI - Influence of block copolymers on the adsorption of plasma proteins to microspheres. AB - SDS-PAGE in combination with densitometry has been used to evaluate the adsorption of plasma and serum proteins to polystyrene microspheres (PS) coated with block copolymers of the poloxamer and poloxamine series. The protein resistant nature of coated PS was demonstrated for these systems when incubated in dilutions of plasma and serum. The total amount of protein and the type of proteins adsorbed were dependent on the plasma and serum incubation concentration used. At 0.3% serum concentrations the total amount of protein adsorbed was found to be related to the polyoxyethylene (PEO) chain length of the block copolymer, whilst at 0.3% or 50% plasma concentrations a relationship was shown between the polyoxypropylene (PPO) chain and the plasma protein adsorption for the range of block copolymers studied. Immunoblotting studies revealed the adsorption of immunoglobulin G, complement C3, transferrin and fibronectin to all microspheres previously incubated in 50% serum and plasma, whilst fibrinogen was also adsorbed after incubation in 50% plasma; with similar quantities of each protein adsorbed to PS and block copolymer-coated PS. PMID- 8476993 TI - Regulation by sulphonate groups of complement activation induced by hydroxymethyl groups on polystyrene surfaces. AB - Reducing the complement-activating capacity of a polymer surface is important in improving its blood compatibility. Polystyrene surfaces bearing hydroxymethyl (CH2OH) groups activate the alternative pathway of complement. This activation depends strongly on the density of the groups. Polystyrene surfaces bearing sulphonate (SO3-) groups adsorb proteins, resulting in an apparent activation. Polystyrene surfaces bearing both types of groups in close proportions are not activators in human serum, due to the adsorption of a protein of the alternative pathway, which has a protecting effect, not found when a polymer surface bearing hydroxyl groups is mixed in serum with another polymer surface bearing SO3- groups. In the presence of purified proteins of alternative pathway, C3 convertase activity can be created on each of these surfaces by deposition of C3b, but their susceptibility to inactivation by regulatory proteins H and I depends on the types of chemical groups present on the surface and whether the surfaces were passivated or not before C3b deposition. PMID- 8476994 TI - Soft tissue reaction to collagen-immobilized porous polyethylene: subcutaneous implantation in rats for 20 wk. AB - Collagen-immobilized porous polyethylene, in which the immobilization was through covalent bonding, and virgin porous polyethylene were implanted subcutaneously in rats from 1 to 20 wk. The results were the ingrowth of the connective tissue into collagen-immobilized porous polyethylene was rich and contained a low level of inflammatory cellular infiltration compared with that of virgin porous polyethylene. The material-tissue interface showed that the living body originated collagen fibres were firmly anchored into the immobilized collagen layer. These results suggested that covalent immobilization of collagen on to the biomaterial surface is useful in promoting the ingrowth of soft tissue and the tissue adhesion. PMID- 8476995 TI - Histopathological and immunological investigations of synthetic fibres and structures used in three prosthetic anterior cruciate ligaments: in vivo study in the rat. AB - Three types of prosthetic anterior cruciate ligaments were investigated by enzymatic and histological analysis of the tissue surrounding each implant and immunologically by a cytofluorometric analysis of T-cell populations in the peripheral blood of rats. Two of the prostheses had a braided construction, one made from polyester and the other from high performance polyethylene fibres. The third type also contained high performance polyethylene fibres, but had been manufactured in a knitted construction (Raschel high performance polyethylene). Five specimens from each prosthesis were implanted intraperitoneally in rats by a trocar for different periods of time up to 4 wk. A control group of rats underwent the surgery, but not the implant. No modification in peripheral T-cell populations was induced by the presence of any implant. Whilst the levels of acid phosphatase and esterase activity appeared to have increased slightly following implantation of any of the prostheses, such increases were not highly significant. Histologically, all three materials induced an intense acute inflammatory reaction at 3 d which gave way to a typical chronic response after 4 wk. The only major difference between the prostheses was that after 4 wk the polyester fibres exhibited less inflammation, and the surrounding tissue was more mature, more vascularized and more densely infiltrated with collagen than with the two high performance polyethylene implants. In conclusion, all three devices provided satisfactory biocompatibility in terms of cellular and healing response. PMID- 8476996 TI - Cell seeding in porous transplantation devices. AB - Porous laminated discs of 1.35 cm diameter and thickness of 0.5 cm fashioned from biodegradable polymers were used as scaffolds for the transplantation of isolated cell populations. The distribution of cells seeded in these devices via injection was modelled with a system of dyed polymeric microparticles. Optimization of parameters related to device design and surgical injection conditions was carried out to maximize the device volume effectively employed in cell transplantation. The area of distribution on the top surface of each device was determined by image analysis techniques and used as a measure of the spatial distribution of injected particles. For poly(L-lactic acid) devices of porosity of 0.83 and median pore diameter of 166 microns seeded with 6 microns beads under standard injection conditions, the average surface area of distribution was 44.45% (+/- 3.36%). The device pore size was found to be a crucial determinant of particle distribution, whilst particle size in the range of 1-10 microns was not found to be important for the devices tested. Application of these results to the seeding of hepatocyte suspensions was made. PMID- 8476997 TI - Imaging surfaces of hydrophilic contact lenses with the atomic force microscope. AB - Soft contact lens (SCL) surfaces were imaged with atomic force microscopy (AFM). High-resolution images of unworn SCL were obtained under nearly physiological medium. We present images of surfaces of collagen bandage lens under dry or aqueous conditions and of SCL of different water content and fabrication processes. Roughness parameters were determined. AFM studies of surfaces of SCL are expected to provide useful information on the hydrogel surfaces. PMID- 8476998 TI - Biocompatibility of polyoxymethylene (Delrin) in bone. AB - The bone tissue reaction to bulk polyoxymethylene (Delrin) was studied in eight adult albino rabbits followed for up to 5 months after insertion of implants into the tibial metaphyses. Each animal received two implants, one of pure Delrin, the other a 'mosaic' plug with alternating areas of commercially pure titanium and Delrin. At the passage through the cortex, a direct bone-Delrin contact was seen in more than half of the cases, but the contact was usually limited in extent. At the same time, in virtually all sections, a foreign-body reaction with macrophages and giant cells was prominent. It was concluded that bulk Delrin has inferior biocompatibility to titanium, and the advisability of using Delrin as a biomaterial for bone anchorage is questionable. PMID- 8476999 TI - Poly(L-lactide): a long-term degradation study in vivo. Part III. Analytical characterization. AB - Three poly(L-lactides) with different molecular weights were synthesized as solid blocks from the melt. Two batches were ground and small specimens were produced by injection moulding. The third block was processed by machining, yielding crystalline parts. All were implanted as small rods into the dorsal muscle of rats. The implants were recovered, weight loss was determined, and the samples analysed. The samples degraded very fast, reaching the same molecular weight level after 20 wk, then degraded simultaneously. Analysis showed differences depending on the solid state of the polymer. The differences in the degradation behaviour of the amorphous and crystalline samples can be explained by assuming a simple hydrolysis as the main degradation mechanism, affecting the whole polymer, if in an amorphous state, but only the amorphous domains in a crystalline polymer. PMID- 8477000 TI - Intramedullary nailing of the cortical bone osteotomies in rabbits with self reinforced poly-L-lactide rods manufactured by the fibrillation method. AB - Right femoral, cortical bone osteotomies of 42 rabbits were fixed with fibrillated, self-reinforced (SR) poly-L-lactide (PLLA) rods, 4.5 mm in diameter. Follow-up times were from 3 to 48 wk. None of the rods broke during this period. There was one non-union at three weeks and one non-union at 12 weeks. Radiographic, histologic, microradiographic and oxytetracyclic fluorescence studies showed normal healing. Shear load carrying capacity of the osteotomy plane was measured from 30 bone samples; the shear force at breaking increased during the follow-up time to 450 N, while the mean shear force of intact, left side control femurs was 440 N. Before shear tests of the bones, the SR-PLLA rods were taken away from the medullary cavities of the femurs. The rods were also tested mechanically. About 25% of the initial 136 MPa shear-strength of the rods was left after 24 wk. The results show that fibrillated SR-PLLA rods are strong enough to be used in intramedullary nailing of femoral cortical bone osteotomies in rabbits. PMID- 8477001 TI - Physical-mechanical effects of Nd:YAG laser on the surface of sound dental enamel. AB - Human dental enamel samples were irradiated using a 5 kHz Q-Switched Nd:YAG laser. An increase in Knoop microhardness and modification of the membrane permselectivity were detached. These results and the changes observed by SEM, can be connected with the fusion of the enamel surface. PMID- 8477002 TI - Elastin patches. PMID- 8477003 TI - Sources and role of iron in lipid peroxidation. PMID- 8477004 TI - Immunochemical detection of liver protein adducts of the nonsteroidal antiinflammatory drug diclofenac. AB - Serious idiosyncratic hepatic injury has been associated with the use of many nonsteroidal antiinflammatory drugs, including the widely prescribed agent diclofenac. In order to investigate the possibility that covalent protein adducts of reactive metabolites of diclofenac might be responsible for the hepatotoxicity produced by this drug, we have developed a polyclonal antibody that can recognize such adducts in tissues. Immunoblotting revealed that protein adducts of reactive metabolites of diclofenac of 50, 70, 110, and 140 kDa were formed in the livers of mice treated with diclofenac. In the future, it will be determined whether these adducts can cause hepatotoxicity by either a hypersensitivity or metabolic mechanism. Similar approaches may be used to study the protein adducts and mechanisms of hepatotoxicity of other nonsteroidal antiinflammatory drugs. PMID- 8477005 TI - Chemical characterization and toxicity of dihydro derivatives of nodularin and microcystin-LR, potent cyanobacterial cyclic peptide hepatotoxins. AB - Dihydro derivatives of nodularin (1) and microcystin-LR (4), potent cyclic peptide hepatotoxins isolated from Nodularia spumigena and Microcystis aeruginosa, respectively, were prepared by sodium borohydride reduction of the dehydroamino acid residues. The two stereoisomers of both dihydronodularin (2 and 3) and dihydromicrocystin-LR (5 and 6), isolated by reversed-phase HPLC, showed similar toxicity to each other [ip in mice, LD50 = 150 (2), 150 (3), 85 (5), and 100 (6) micrograms/kg]. The stereochemistries of the reduced amino acids obtained by acid hydrolysis of dihydronodularin and dihydromicrocystin-LR [respectively, alpha-(methylamino)butyric acid and N-methylalanine] were determined by GC on a permethylated beta-cyclodextrin capillary column as their trifluoroacetyl methyl ester derivatives. Authentic L- and DL-N-methylamino acids were prepared to compare directly with the natural amino acids. Deuterated derivatives were also prepared using sodium borodeuteride (98 atom % D), and the location (beta) and percentage (78-84%) of the deuterium incorporation were determined. PMID- 8477006 TI - Reaction of nontoxic, potentially chemopreventive purinethiols with a direct acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide. AB - Several nontoxic purinethiols have been shown to block the ability of the carcinogen 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) to bind covalently to DNA in Chinese hamster ovary cells. Two of these compounds also block BPDE-induced tumorigenesis in a two-stage mouse skin carcinogenesis model. The suggested mode of action of the purinethiols is through scavenging the electrophilic carcinogen by way of covalent reaction with the purinethiol. In the present work, we demonstrate that a series of five purinethiols (2,6-dithiopurine, thiopurinol, 6-thioxanthine, 2-mercaptopurine, and 9-methyl-6-mercaptopurine) react covalently in vitro with BPDE. The adducts formed have been characterized by UV-visible spectroscopy, solvent partitioning, and NMR spectroscopy; they result from addition of the thiol moiety at the 10 carbon of BPDE. Studies of the effects of Tris buffer and temperature on product ratios at completion of reaction indicate that the two major reaction pathways, hydrolysis of the epoxide and adduct formation, do not share a common rate determining step. This suggests that the reaction mechanism for adduct formation is through SN2 attack of the thiol moiety at the 10 position of BPDE. The activation energies for the reaction of 5-purinethiols with various combinations of substituents at the 2 and 6 positions are all very similar, implying closely similar transition states. For compounds with a low pKa (2,6-dithiopurine, 2 mercaptopurine, and 6-thioxanthine) the most important reactant at physiological pH is the thiolate anion. However, for compounds with pKa's above 8, the physiologically important reactions appear to be more complicated. PMID- 8477007 TI - N-nitroso-N-methylvinylamine: reaction of the epoxide with guanyl and adenyl moieties to yield adducts derived from both parts of the molecule. AB - N-Nitroso-N-methylvinylamine was synthesized and treated with dimethyldioxirane to produce 1-(N-nitrosomethylamino)oxirane. 1-(N-Nitrosomethylamino)oxirane had a t1/2 of < 5 s in buffer at neutral pH and 23 degrees C. This epoxide reacted with Ado to form 1,N6-etheno(epsilon-)Ado. It also reacted with DNA to form products arising from the oxirane portion of the molecule [N7-(2-oxoethyl)Gua,N2,3-epsilon Gua, and 1,N6-epsilon-dAdo] and the methyl group (N7-methylGua). NADPH-fortified rat liver microsomes oxidized N-nitroso-N-methylvinylamine to form 1,N6-epsilon Ado in the presence of Ado. Further, 1,N6-epsilon-Ado was also formed in microsomal incubations containing N-nitroso-N-methylethylamine, indicating that desaturation of the ethyl moiety occurs to form a vinyl group and then an epoxide. When NADPH-fortified microsomes were incubated with N-nitroso-N methylvinylamine, HCHO was formed, and when DNA was included in incubations, 1,N6 epsilon-dAdo and N7-methylGua were isolated from DNA. In the cases of both HCHO and N7-methylGua, product formation was similar to the levels seen with N-nitroso N,N-dimethylamine and N-nitroso-N-methylethylamine. PMID- 8477008 TI - Possible role of thioformamide as a proximate toxicant in the nephrotoxicity of thiabendazole and related thiazoles in glutathione-depleted mice: structure toxicity and metabolic studies. AB - In mice depleted of GSH by treatment with buthionine sulfoximine (BSO), thiabendazole (TBZ) causes renal injury characterized by an increase in serum urea nitrogen (SUN) concentration and by tubular necrosis. Previous studies have shown that TBZ requires metabolic activation before it produces nephrotoxicity and that the structure contributing to the toxicity of TBZ is the thiazole moiety of the molecule. TBZ and its thiazole analogues were examined for the ability to increase SUN concentration and serum alanine aminotransferase activity in GSH depleted mice. Unsubstituted thiazole and thiazoles with 4- and/or 5-, and no 2-, substituents caused marked increases in SUN concentration, suggesting nephrotoxicity. Furthermore, the nephrotoxic potency of these thiazoles decreased with the increasing number and bulk of the 4- and/or 5-substituents. On the other hand, the target organ (the kidney or liver) and the toxic potency of 4 methylthiazoles were markedly altered with the type of substituents at the 2 position. These observations and the known toxicity of thiono-sulfur compounds led us to the hypothesis that the nephrotoxic thiazoles, which lack 2 substituents, would undergo microsomal epoxidation of the C-4,5 double bond and, after being hydrolyzed, the resulting epoxide would then be decomposed to form thioformamide, a possibly toxic metabolite. Evidence for this hypothesis was provided by the results that thioformamide and tert-butylglyoxal as the accompanying fragment were identified as urinary metabolites in mice dosed with 4 tert-butylthiazole and that thioformamide caused a marked increase in SUN concentration when administered to mice in combination with BSO. PMID- 8477009 TI - Hepatic cytochrome P450 2B-type induction by ethyl/phenyl-substituted congeners of phenobarbital in the rat. AB - As part of an investigation of the structural requirements for the induction, by phenobarbital-type inducers, of a coordinate pleiotropic response consisting of increases in hepatic cytochrome P450 2B (P450 2B) activity, increases in other phase I and II enzyme activities, and liver hypertrophy, we have examined a series of analogues of phenobarbital in which the ethyl/phenyl substitution at the sp3 carbon of the parent molecule was kept constant while the heterocyclic portion of the molecule was modified. The induction of hepatic P450 2B protein and ethoxy-, pentoxy-, and (benzyloxy)resorufin O-dealkylation activities, and epoxide hydration activity and liver/body weight ratio increase were examined in male F344/NCr rats fed the various congeners for 14 days at doses equimolar to 500 ppm phenobarbital. Increases in the measured parameters were maximal in rats fed phenobarbital or 5-ethyl-5-phenylhydantoin. The responses to primidone or 2 ethyl-2-phenylsuccinimide were approximately 65% of maximal, while glutethimide yielded a response approximately 50% of maximal. Induction of this response in rats fed the ring-opened and decarboxylated analogues, (ethylphenylacetyl)urea and 2-ethyl-2-phenylmalonamide, were < 25% of maximal. 5-Ethyl-5 phenyloxazolidinedione caused minimal increases in the measured end points when administered at a dose equimolar to 500 ppm phenobarbital. The profound differences among the congeners in ability to induce P450 2B protein and associated catalytic activities were not due to differences in food consumption by the various groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477010 TI - Pharmacodynamics of cytochrome P450 2B induction by phenobarbital, 5-ethyl-5 phenylhydantoin, and 5-ethyl-5-phenyloxazolidinedione in the male rat liver or in cultured rat hepatocytes. AB - The pharmacodynamics of rat hepatic cytochrome P450 2B (P450 2B) induction by phenobarbital (PB) and two structural congeners, dl-5-ethyl-5-phenylhydantoin (EPH) and dl-5-ethyl-5-phenyloxazolidinedione (EPO), were investigated. The in vivo induction of P450 2B was probed in F344/NCr rats by measuring immunoreactive hepatic P450 2B1 protein and by assaying the hepatic 16 beta-hydroxylation of testosterone and O-dealkylation of (benzyloxy)- and pentoxyresorufin. The induction of (benzyloxy)resorufin O-dealkylation activity was also measured in adult rat hepatocyte cultures exposed to the three xenobiotics. The concentration of xenobiotic at the putative active site in the in vivo studies was approximated by measuring serum total xenobiotic levels, while in the hepatocyte culture studies, the nominal xenobiotic concentration in the culture medium was used. Concentration-dependent induction of P450 2B activities was observed in the in vivo and hepatocyte culture studies. The in vivo ED50 values for P450 2B induction were approximately 110, approximately 100, and approximately 3000 dietary ppm (14 days administration) for PB, EPH, and EPO, respectively. The in vivo EC50 values for P450 2B induction were approximately 9, approximately 6, and approximately 130 microM (total serum) for PB, EPH, and EPO, respectively. In cultured rat hepatocytes, the ED50 values for induction of (benzyloxy)resorufin O dealkylation activity were 14.5, 14.2, and 108 microM for PB, EPH, and EPO, respectively. These data indicate that pharmacodynamic results obtained with cultured hepatocytes represent a good qualitative and quantitative approximation of the in vivo hepatic responses in male rats caused by PB-type inducers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477011 TI - Investigation of the mechanistic basis of N,N-dimethylformamide toxicity. Metabolism of N,N-dimethylformamide and its deuterated isotopomers by cytochrome P450 2E1. AB - Dimethylformamide (DMF) is an industrial solvent with hepatotoxic properties. The toxicity of DMF has been associated with its metabolism to S-(N methylcarbamoyl)glutathione (SMG). The major urinary metabolite of DMF is N (hydroxymethyl)-N-methylformamide (HMMF). HMMF undergoes oxidation in the formyl moiety, possibly via the intermediacy of its hydrolysis product N-methylformamide (NMF), and the reactive intermediate thus generated reacts with glutathione to yield SMG. Experiments were conducted to elucidate enzymatic details of the metabolism of DMF. Generation of HMMF from DMF in microsomes from rats which had received acetone, an inducer of cytochrome P450 2E1, was increased by 175% over that observed in control microsomes. In liver microsomes from 4 humans the metabolism of DMF to HMMF was inhibited by a monospecific antibody against rat liver P450 2E1, and the metabolic rates were correlated with those of NMF to SMG, a process known to be mediated via P450 2E1. DMF was also metabolized by purified rat liver P450 2E1. The kinetic parameters which characterize the metabolism of DMF or its deuterated isotopomers to the respective HMMF isotopomers, of HMMF to SMG and of NMF to SMG in liver microsomes, were computed from Eadie-Hofstee plots. The affinity of DMF for the metabolizing enzyme in rat liver microsomes is considerably higher (apparent Km = 0.20 mM) than that of NMF (Km = 4.28 mM) or of HMMF (Km = 2.52 mM). The respective values observed with human microsomes are very similar. The apparent Km values for the N-methyl oxidation of N,N dimethyldeuterioformamide ([2H1]DMF) and N,N-bis(trideuteriomethyl)formamide ([2H6]DMF) in rat microsomes are 0.14 and 0.21 mM, respectively. The apparent Vmax for the oxidation of [2H1]DMF is similar to that computed for DMF, and the Vmax for [2H6]DMF is less than half of that computed for DMF. The kinetic deuterium isotope effect (KDIE) on DMF metabolism was determined in incubations with rat microsomes in three ways: (i) the noncompetitive intermolecular KDIE by the ratio of Vmax/Km for DMF to Vmax/Km for [2H6]DMF, (ii) the competitive intermolecular KDIE as the quotient of metabolic products HMMF to N (hydroxydideuteriomethyl)-N-(trideuteriomethyl)formamide in incubations of DMF together with [2H6]DMF, and (iii) the intramolecular KDIE as the quotient of the ratio of N-(hydroxymethyl)-N-(trideuteriomethyl)formamide to N (hydroxydideuteriomethyl)-N-methylformamide generated from N-(trideuteriomethyl) N-methylformamide ([2H3]DMF). The respective values were found to be (i) 2.4, (ii) 5.0, and (iii) 5.2. DMF inhibited the oxidation of NMF or HMMF to SMG.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477012 TI - Bihaptens with 5- and 6-methyl-substituted alkylcatechols and methylene lactone functional groups: tools for hapten (allergen or tolerogen)-protein interaction studies. AB - In order to investigate hapten-protein interactions in vivo, potential skin sensitizers 1-3, with two different haptenic ends, (a) a catechol, a 5 methylcatechol, and a 6-methylcatechol respectively, and (b) an alpha-methylene gamma-butyrolactone moiety, separated by a straight 10-carbon chain, have been prepared and used to sensitize guinea pigs. Related "monohapten lactones" 19-21, containing an electrophilic alpha-methylene-gamma-butyrolactone moiety connected to the protected catechol structures, and "monohapten catechols" 25-27, containing a reduced alpha-methyl-gamma-butyrolactone linked to the catechol, also have been prepared. Bihaptens 1 and 2 which were found to have very close biological activities appear to react with proteins through the catechol ring, indicating a low importance of the C-6 position in the binding of catechols with amino acids. In contrast, bihapten 3 was found to react through both the catechol and lactone ring. The influence of amino and thiol binding sites on the biological activity (allergy or tolerance) as well as the influence of the sensitizing method are discussed. PMID- 8477013 TI - Formation, characterization, and immunoreactivity of lysine thioamide adducts from fluorinated nephrotoxic cysteine conjugates in vitro and in vivo. AB - Fluorinated nephrotoxic cysteine conjugates undergo bioactivation via the beta lyase pathway to thionoacetyl fluorides (TAF), the putative reactive intermediates. The TAF derived from S-(1,1,2,2,-tetrafluoroethyl)-L-cysteine (TFEC) difluorothionoacetylates amine nucleophiles found in proteins and lipids. A specific antisera, raised against (trifluoroacetamido)lysine adducts formed in vivo after halothane treatment, has previously been used to localize TFEC-derived protein adducts immunohistochemically, and a good correlation between adduction and toxicity was demonstrated. Interestingly, thioamide formation is facilitated by acyl-transfer catalysts such as imidazoles and phenols. However, although putative lysine adducts have been reported to be formed from the related TAF derived from S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), protein adducts derived from CTFC metabolism have not been completely characterized. In the present investigation we characterize (chlorofluorothionacetamido)lysine (CFTAL) adduct formation during S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) metabolism, both in vitro and in vivo. Our data indicate that formation of CTFC derived lysine thioamides was not as dependent on nucleophilic catalysis as observed for TFEC, and this appears to be due to an apparent greater reactivity of the TAF resulting in a higher trapping efficiency in the absence of catalyst. Also, qualitative and quantitative differences in the structures and time course of CTFC versus TFEC adduct breakdown were observed. Antibodies raised against the halothane metabolite protein adduct (trifluoroacetamido)lysine cross-react with specific mitochondrial proteins from the kidneys of TFEC-treated rats. Using this antibody, we have found that the pattern of adducted proteins from TFEC- and CTFC treated Fischer rats was similar, but the intensity was considerably lower after treatment with equimolar concentrations of CTFC in vivo. PMID- 8477014 TI - Inhalation-based anesthetic techniques are the key to early extubation of the cardiac surgical patient. PMID- 8477015 TI - The effect of a cardiac surgical recovery area on the timing of extubation. AB - The anesthetic and postoperative management of cardiac surgical patients was modified to achieve an early return to spontaneous ventilation. A total of 278 patients were studied to determine the effect of this change. Patients in group I (n = 198) were managed in a cardiac surgical recovery area according to the new policy. Group II (n = 80) was a comparable group of patients operated upon before this change. The median duration of postoperative ventilation was reduced from 5 hours in group II to 1 hour in group I, and the time to extubation was reduced from 7 hours to 2 hours, respectively. There were no major postoperative complications resulting from this change. The factors that influence the duration of postoperative ventilation are discussed. PMID- 8477016 TI - Infusion of propofol versus midazolam for sedation in the intensive care unit following coronary artery surgery. AB - The use and the hemodynamic effects of propofol and midazolam were studied during titrated continuous infusions to deep sedation (sedation level 5: asleep, sluggish response to light glabellar tap or loud auditory stimulus) following coronary artery surgery. The drugs were compared in 30 ventilated patients in an open randomized study. The duration of infusion was approximately 570 minutes in both groups. After a loading dose of propofol (1 mg/kg) or midazolam (0.07 mg/kg), the infusion rates were 2.71 +/- 1.13 mg/kg/h and 0.092 +/- 0.028 mg/kg/h, respectively. An analgesic infusion of sufentanil was also given in both groups. In the midazolam group, to maintain the predetermined level of sedation, more frequent additional bolus doses (4.7 +/- 1.8; P < 0.001) and infusion rate adjustments (5.3 +/- 1.6; P < 0.001) were required than for similar sedation in the propofol group (2.3 +/- 1.0 bolus doses and 3.3 +/- 1.2 adjustments). The time from stopping sedation to patient responsiveness was 11 +/- 8 minutes in the propofol group and 72 +/- 70 minutes in the midazolam group (P < 0.001), and the time from stopping sedation to extubation was 250 +/- 135 minutes and 391 +/- 128 minutes (P < 0.014), respectively. Following the loading dose of propofol, there was a fall in blood pressure (BP) (mean from 80 +/- 11 mmHg to 67.5 +/- 10 mmHg; P < 0.05). After approximately 15 minutes, BP started to rise but remained below pretreatment level throughout sedation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477017 TI - Postoperative analgesia and sedation following pediatric cardiac surgery using a constant infusion of ketamine. AB - Constant rate infusions of ketamine supplemented with intermittent doses of midazolam were given postoperatively to 10 children in order to provide analgesia and sedation during mechanical ventilation after cardiac surgery as well as during weaning from the ventilator and during spontaneous breathing. The aims of the study were to determine the pharmacokinetics of ketamine and evaluate the suitability of ketamine as an analgesic and sedative in postoperative pediatric cardiac patients. The children were between one week and 30 months old. Five children were given 1 mg/kg/h of ketamine and five children had 2 mg/kg/h. Blood was sampled during infusion and up to 24 hours after infusion for plasma concentrations of ketamine and the main plasma metabolite, norketamine, which were determined by gas chromatography and were compared to the degree of sedation. The children were arousable when ketamine concentrations were below 1.0 to 1.5 micrograms/mL. Plasma ketamine concentrations at steady state were within a narrow range for each infusion regimen and the calculated pharmacokinetic parameters were similar. Mean plasma clearance of ketamine was 0.94 +/- 0.22 L/kg/h. The elimination half-life was 3.1 +/- 1.6 hours, but in some children late samples indicated an even longer elimination half-life. Norketamine did not reach a steady state, but at the end of the infusion, the mean plasma concentration was higher than that of ketamine. The elimination half-life of norketamine was estimated to be 6.0 +/- 1.8 hours. Both ketamine infusion regimens were supplemented with midazolam and provided similarly acceptable analgesia and sedation during mechanical ventilation and during and after weaning from the ventilator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477018 TI - Intrathecal morphine during thoracotomy, Part I: Effect on intraoperative enflurane requirements. AB - The ability of intrathecal morphine to reduce the anesthetic requirements during thoracotomy was investigated. Twenty-four patients scheduled for thoracic surgery were studied. Anesthesia was induced with thiamylal sodium, 4 mg/kg, fentanyl, 100 micrograms, and 100 mg of succinylcholine. Prior to skin incision, 12 patients received intrathecal injection of 12 micrograms/kg of preservative-free morphine sulfate (ITM), while the remaining 12 patients served as controls. The ITM was given undiluted at the L3-4 or L4-5 level. Anesthesia was maintained solely with enflurane, titrated to keep mean arterial pressure within 15% of the preoperative values. Vecuronium was given as required for relaxation. No additional narcotics were administered. Throughout the procedure, end-tidal (ET) enflurane concentration was recorded at 15-minute intervals from the mass spectrometer (Perkin Elmer). The intraoperative mean ET concentration of enflurane was significantly reduced in the ITM group beginning 1 hour after the injection (1.19 +/- .45% in the control group versus 0.73 +/- 0.08% in the ITM group). The enflurane requirements, expressed as percent end-tidal enflurane/hour, were significantly less in the ITM group for the duration of the procedure (0.8 +/- .17 v 1.08 +/- .22, respectively). In conclusion, when administered prior to skin incision for post-thoracotomy pain control, intrathecal morphine reduces intraoperative enflurane requirements. PMID- 8477019 TI - Intrathecal morphine during thoracotomy, Part II: Effect on postoperative meperidine requirements and pulmonary function tests. AB - The ability of intrathecal morphine (ITM) to reduce post-thoracotomy pain and meperidine requirements was investigated. Thirty adult patients scheduled for thoracic surgery were studied. Following induction with thiamylal sodium and succinylcholine, anesthesia was maintained with 100 micrograms of fentanyl, vecuronium, and enflurane. Prior to skin incision, 16 patients received intrathecal morphine, 12 micrograms/kg, injected at the L3-4 or L4-5 level. The other 14 patients were controls. Postoperatively, patients were evaluated for pain scores and the total doses of meperidine required over 24 hours. The patients in the ITM group required significantly less meperidine compared to the control group (59 +/- 68 v 167 +/- 97 mg, respectively) and had lower pain scores (1.4 +/- 1.1 v 2.4 +/- 0.9 mg, respectively). There were no serious side effects attributable to ITM. It is concluded that ITM is an effective adjunctive treatment for control of post-thoracotomy pain. PMID- 8477020 TI - Transesophageal two-dimensional echocardiographic analysis of right ventricular systolic performance indices during coronary artery bypass grafting. AB - Sixteen patients (aged 59 +/- 14 years) undergoing coronary artery bypass surgery were evaluated to delineate the intraoperative course of transesophageal echocardiographic right ventricular (RV) systolic performance indices. Pre induction data included thermodilution RV ejection fraction (RVEFTD), 0.43 +/- 0.13, RV end-diastolic volume index (EDVI), 110 +/- 33 mL/m2, cardiac index (CI), 3.4 +/- 1.0 L/min/m2, RV end-diastolic pressure (EDP), 7.1 +/- 4.2 mmHg, and mean pulmonary artery pressure (PAP), 21 +/- 6 mmHg. Eleven patients had significant right coronary artery (RCA) disease (> 70% occlusion). Five patients arrived with an ongoing nitroglycerin infusion (1 to 3 micrograms/kg/min), which was maintained intraoperatively. Echocardiographic measurements included longitudinal axis (LA) and short-axis (SA) planimetered area excursion fractions (2DLA and 2DSA, respectively) and LA maximal major and minor axis shortening fractions (max majorLA and max minorLA, respectively). Hemodynamic measurements included RVEFTD, EDVI, CI, EDP, and PAP. Measurements were determined following induction/endotracheal intubation, following sternotomy/pericardiotomy, and after cardiopulmonary bypass (CPB) with the chest open. All patients were maintained on vasodilator therapy post-CPB (nitroglycerin, 1 to 3 micrograms/kg/min [N = 16] and nitroprusside, 0.5 to 4.5 microgram/kg/min [N = 4]) post-CPB. Two patients received inotropic support (epinephrine, 0.2 to 0.3 microgram/kg/min). CPB was associated with significant decreases in max major axisLA and 2DLA (P < 0.05) as compared to measurements determined prior to CPB. Maximum major axisLA values pre CPB were 0.35 +/- 0.06 and 0.33 +/- 0.08 versus post-CPB values of 0.24 +/- 0.08.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477021 TI - The relationship between "normal" transesophageal color-flow Doppler-defined tricuspid regurgitation and thermodilution right ventricular ejection fraction measurements. AB - Twenty coronary artery revascularization patients, aged 58 +/- 15 years, were studied intraoperatively to define the impact of Doppler-defined tricuspid regurgitation on measurement of thermodilution right ventricular ejection fraction (50 msec response pulmonary artery catheter). Right ventricular function was also estimated using a measurement technique independent of flow patterns across the tricuspid valve (transesophageal two-dimensional echocardiographic 5.0 MHz phased-array transducer). Measurements included transverse plane long- and short-axis planimetered area ratio, respectively, and tricuspid annular plane systolic excursion ratio (ratio = end-diastolic minus end-systolic value divided by end-diastolic value). Data were expressed as thermodilution-echocardiographic gradients, ie, thermodilution ejection fraction minus long-axis planimetered area ratio, short-axis planimetered area ratio, and tricuspid annular plane systolic excursion ratio, respectively. Tricuspid regurgitation was quantified by color flow Doppler perimetry of maximal regurgitation jet area and analysis of transduced right atrial pressure waveform. Doppler estimates were expressed as absolute values and as a function of corresponding atrial area (tricuspid regurgitation index = planimetered jet area divided by right atrial area). Data were obtained following endotracheal intubation, sternotomy, pericardiotomy, cardiopulmonary bypass, and chest closure. Data were evaluated by regression analysis, with separate analyses performed for each time period. Profiles were unassociated with right atrial pressure waveform abnormalities. There was no significant relationship between thermodilution ejection fraction variance values and tricuspid regurgitation jet area or regurgitation index, respectively. In each measurement period, thermodilution-echocardiographic gradients were also unrelated to the tricuspid regurgitation estimates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477022 TI - Low risk of gastroesophageal injury associated with transesophageal echocardiography during cardiac surgery. AB - Transesophageal echocardiography (TEE) has increasingly been used in cardiology and cardiac surgery with few reported complications. This study was undertaken to determine whether TEE is associated with an increased incidence of gastroesophageal (GE) bleeding or postoperative GE symptoms of anorexia, dysphagia, or sore throat. Forty-one patients who underwent TEE during cardiac surgery and 40 control patients who underwent cardiac surgery without TEE were prospectively followed. In addition, a retrospective chart review of 200 patients who underwent TEE during cardiac surgery was also performed. The following information was derived from the patient interviews and chart reviews: (1) The development of both frank and occult upper gastrointestinal tract (UGI) bleeding; (2) the patient's preoperative anticoagulation status; and (3) the patient's subjective complaints of anorexia, dysphagia, or sore throat. The incidence of postoperative occult or frank UGI bleeding was not increased in the groups who underwent TEE. Additionally, the incidence of postoperative GE symptoms was comparable in the three groups. These findings are discussed in the context of reported complications associated with UGI endoscopy. Based on this analysis, recommendations for the safe performance of TEE have been provided. PMID- 8477023 TI - Percutaneous pericardiocentesis versus subxiphoid pericardiotomy in cardiac tamponade due to postoperative pericardial effusion. AB - In a retrospective study, 42 patients with acute cardiac tamponade due to pericardial effusion were evaluated following cardiac surgery, and the pericardial fluid was drained by one of two alternative methods: two-dimensional echocardiographic-guided pericardiocentesis (2D-echo) or subxiphoid surgical pericardiotomy. During the first period (from 1982 to 1986), one of the two methods was chosen by the treating physicians, whereas in the second period (from 1986 to 1991), 2D-echo-guided pericardiocentesis was the treatment of choice. Percutaneous pericardiocentesis was performed using local anesthesia in 29 patients. A Tuohy needle was inserted at the left xipho-costal junction and, when fluid was obtained, 6 mL of saline solution was injected during 2D-echo contrast monitoring, and a multiple-hole, 6F, 30-cm catheter was inserted by means of a guidewire and positioned into the posterior pericardium, as near as possible to the atrioventricular groove. Complete drainage of pericardial fluid by percutaneous pericardiocentesis was obtained in 26 patients (89%). This procedure also allowed the evacuation of posterior and loculated effusions. Complications included two right ventricular punctures, which were immediately recognized by 2D echo contrast and produced no serious consequences. Sixteen patients who underwent surgical pericardiotomy had complete evacuation of pericardial fluid without major complications (two of them suffered atrial arrhythmias during the procedure). The average amount of fluid drained, as well as the localization of the effusions, were the same for both groups. 2D-echo-guided pericardiocentesis was found to be a useful, safe, and simple technique. It can be used as an alternative treatment to subxiphoid pericardiotomy for cardiac tamponade due to postoperative pericardial effusions. PMID- 8477024 TI - Potential risks of high-dose epinephrine for resuscitation from ventricular fibrillation in a porcine model. AB - The arterial plasma concentrations and hemodynamic effects of epinephrine, 10 micrograms/kg, IV (group A, N = 8) and 50 micrograms/kg, IV (group B, N = 8) were compared in a porcine resuscitation model after 3 minutes of circulatory arrest induced by ventricular fibrillation. All animals in group A were successfully resuscitated after 4.9 +/- 2.8 minutes and 2.8 +/- 1.6 defibrillations. In group B, only 6 of 8 animals were successfully resuscitated after 6.3 +/- 1.1 minutes and 4.0 +/- 2.7 defibrillations (mean +/- SD). During CPR, cardiac output (CO), left ventricular systolic pressure (LVSP), and mean arterial pressure (MAP) were nearly identical in the groups. The hemodynamic situation during the first hour after restitution of spontaneous circulation in group B was characterized by a significantly higher heart rate, combined with significantly lower values for cardiac inotropy, CO, LVSP, and MAP compared to group A. Mean arterial peak epinephrine concentrations (group A 197 +/- 133 ng/mL, group B 1173 +/- 298 ng/mL) were approximately fivefold higher in group B. After resuscitation, plasma concentrations returned to baseline levels within 7 minutes in group A and 15 minutes in group B. Later hemodynamic differences between the groups are thereby attributed to a detrimental impact of high-dose epinephrine on the heart during resuscitation. PMID- 8477025 TI - Regional distensibility, chamber stiffness, and elastic stiffness constant in halothane and propofol anesthesia. AB - Nine mongrel dogs were acutely instrumented in order to investigate cardiac stiffness at end-diastole while left ventricular circumferential lengths were measured at two different sites (near-apical region and near-basal region). Two hundred mL of autologous blood were infused and then withdrawn to create different volume loading conditions. Four different anesthetic settings were tested: two concentrations (0.7% and 1.7%) of halothane, and two infusion rates (0.2 mg/min/kg, and 0.4 mg/min/kg) of propofol. Three parameters of cardiac stiffness were calculated: distensibility, chamber stiffness (Kp), and elastic stiffness constant (k). Chamber stiffness and elastic stiffness constant were smaller in the apical region than the basal region under halothane anesthesia at both the 0.7% and 1.7% concentrations. There were no regional differences in elastic stiffness constant (k) under propofol anesthesia at either infusion rate. However, Kp was smaller in the apical region at the low propofol infusion rate. There were no significant differences in Kp and k between the anesthetic agents, or with the increase in concentration of either agent. However, when both agent and concentration were taken into consideration, an increase in stiffness was observed with deepening halothane, but not propofol anesthesia. These results show that assessment of diastolic function must take into consideration both regional differences and the anesthetic agent, because the latter may alter such differences and, thus, alter diastolic function. PMID- 8477026 TI - Use of a modified van der Pol's oscillator to construct ventricular pressure volume relations. AB - Ventricular pressure-volume (PV) loops provide information about ventricular function. Methodologic constraints have limited derivation of PV loops to the laboratory. The present study addresses derivation of PV loops from a direct left ventricular pressure measurement and left ventricular volume derived from continuous cardiac output. The measurements were performed in vivo in intact, innervated, normal canine hearts. Data from a total of 5 dogs and 13 different cardiac work states were analyzed. A nonlinear oscillator, a van der Pol's oscillator, described the PV relationships. Comparison of left ventricular stroke work derived from the van der Pol's oscillator model with that obtained from ultrasound transducers sutured directly to the myocardium demonstrated a linear correlation, close to the identity line, with R2 = 0.90. Modelling of LV PV loops by this technique was similar to loops derived by experimental measurements. This technique could lead to increased clinical uses for PV relationships. PMID- 8477027 TI - Major obstruction of the right mainstem bronchus caused by placement of a right axillary roll. PMID- 8477028 TI - The use of high-frequency jet ventilation during post-lung transplantation surgery. PMID- 8477029 TI - Unusual central venous catheter placement in a patient with congenital heart disease. PMID- 8477030 TI - Severe neurologic injury following bidirectional Glenn shunt. PMID- 8477031 TI - Refractory postoperative torsades de pointes syndrome successfully treated with isoproterenol. PMID- 8477032 TI - Antihypertensive drug treatment in the perioperative period. PMID- 8477033 TI - Case 1--1993. Emergency use of cardiopulmonary bypass for resuscitation from CPR resistant cardiac arrest. PMID- 8477034 TI - Right ventricular ejection fraction catheter: toy or tool? Pro: a useful monitor. PMID- 8477035 TI - Right ventricular ejection fraction catheter: toy or tool? Con: a premature step. PMID- 8477036 TI - An unusual transesophageal echocardiogram. Atrial septal aneurysm with patent foramen ovale. PMID- 8477037 TI - Pulmonary artery catheterization after transesophageal echocardiography: what should the sequence be? PMID- 8477038 TI - Thoracic epidural analgesia for cardiac surgery. PMID- 8477039 TI - Catastrophic cardiopulmonary bypass accident. PMID- 8477040 TI - Comments on dynamic cardiomyoplasty. PMID- 8477041 TI - Atrio-ventricular groove rupture diagnosed by perioperative transesophageal echocardiography. PMID- 8477042 TI - Thumb in cheek? Sensory reorganization and perceptual plasticity after limb amputation. AB - We describe a patient who initially suffered from carpal tunnel syndrome that was alleviated by surgery. Subsequently, the patient's right arm was amputated and a phantom limb emerged. Stimuli applied to different areas of the face gave rise to sensations that were referred to the phantom by precise topographic mapping. This perceptual mapping of the (phantom) hand onto the face area modelled the form of prior pathology due to carpal tunnel syndrome. The findings have implications for the relief of phantom pain. PMID- 8477043 TI - Perception of neck rotation assessed by 'remembered saccades'. AB - A new technique for the assessment of cervical afferent function is described. It is based on the perception of trunk rotation around the earth-fixed head and assessed by the accuracy of eye saccades in the direction of trunk displacement. It was found that normal subjects were able to locate trunk position accurately (mean error 15%), independently of trunk displacement amplitude (10-40 degrees) or velocity (5-40 degrees s-1). It is concluded that normal man has accurate perception of trunk rotation and that neck-spinal afferents carry a tonic signal with efficient access to the ocular motor system. A patient with absent vestibular function showed identical results to those of normal subjects; this suggests that the enhancement of the cervico-ocular reflex observed in such patients is not mediated by an increase in neck-spinal afferent sensitivity. PMID- 8477044 TI - The sneeze: maturation of the reflex in kittens. AB - This is the first study to compare the influence of nasal afferent stimulation on inspiratory and expiratory muscle activity during sneezing, in kittens and adult cats. In kittens, we demonstrate that nasal afferent stimulation does not reinforce inspiratory activity prior to the expiratory thrust as it normally does in adult cats. These stimulations evoke an active expiration similar to but weaker than the expiratory thrusts observed under the same conditions during sneezing in adult cats. Sneezing can be elicited from three weeks of life. Among the different hypotheses discussed, the most likely explanation appears to be the immaturity of medullary respiratory connections. PMID- 8477045 TI - High frequency (60-90 Hz) oscillations in primary visual cortex of awake monkey. AB - It has been proposed that synchronized oscillations play a key role in perceptual feature linking and sensory integration. This idea was supported by the discovery of strongly synchronized stimulus-specific oscillations in the visual cortex of anaesthetized cats. The 'synchronization hypothesis' was controversial because in the visual cortex of awake monkeys either only weak or no oscillations were found. We have now recorded high amplitude synchronized oscillation at the level of spike activity and local field potential from the primary visual cortex of an awake monkey. The dominant frequencies (70-80 Hz) were considerably higher than those observed previously in cats and monkeys (30-50 Hz). However, stimulus specificities of the oscillations were comparable to and amplitudes even higher than those in cats. PMID- 8477046 TI - Responses to Ca2+ of two types of excitatory junctional potentials in cricket muscles. AB - Cricket (Gryllus bimaculatus) abdominal muscle 202 produced both small and large excitatory junctional potentials (EJPs) depending on the intensity of the stimulation to the nerve. Abdominal muscle 203 generated only small EJPs. The large EJPs, the threshold of which was always slightly higher than the small EJPs, were more sensitive to the Ca2+ concentration at which they were evoked and to concentration changes. There were no marked differences between the two muscles regarding the electrical properties of the muscle fibre membrane and the quantal size of the transmitter. The causes of the differences between the two types of EJPs in these muscles are discussed. PMID- 8477047 TI - Subtelencephalic visual discrimination in selected lines of Japanese quail. AB - We studied visual discrimination capabilities of the avian brain stem in genetic lines of Japanese quail artificially selected for unconditional approach preference for blue, red or an achromatic pattern stimulus. Complete telencephalectomy did not abolish approach behavior and visual discrimination. Our data indicate that visual feature extraction and motor coordination related to early approach preferences in birds may be mediated by brain stem and thalamic circuitries which do not require input from higher level visual and motor regions. PMID- 8477048 TI - Cortical astrocytosis in juvenile rhesus monkeys infected with simian immunodeficiency virus. AB - The pattern of expression of GFAP immunoreactivity in astrocytes of the juvenile rhesus monkey cortex was examined following infection with simian immunodeficiency virus (SIV). Blocks of cerebral cortex plus subjacent white matter from saline- and formalin-perfused brain were examined by peroxidase linked immunochemical and immunofluorescence staining of deparaffinized sections. Strong GFAP immunoreactivity was found in astrocytic cells in both uninfected and SIV-infected juvenile macaque in the subpial cerebral cortex and in subcortical white matter, where GFAP-positive cells were abundant. GFAP staining of cortical layers 2-6 on the other hand was weak or absent in three uninfected controls and one infected animal without cognitive impairment, but moderate to strong in animals productively infected with SIV that demonstrated cognitive and/or motor impairment. These data demonstrate a cortical locus of astrocytic activation in rhesus monkeys infected with primate immunodeficiency virus isolate SIVB670 which, like HIV-1 in man, causes motor/cognitive impairment as well as immunodeficiency disease. PMID- 8477049 TI - Inhibition of nitric oxide synthesis impairs autoregulation of local cerebral blood flow in the rat. AB - The effect of intravenous administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg kg-1), a specific inhibitor of nitric oxide (NO) synthesis, on the autoregulation of local cerebral blood flow (LCBF) was examined in the rat using the [14C]iodoantipyrine autoradiographic method. LCBF was significantly lower in various superficial regions such as the cerebral cortices and cerebellar cortex and in several deep brain regions in animals with haemorrhagic hypotension induced after L-NMMA infusion (the L-NMMA + HEM group) compared with animals without haemorrhagic hypotension after L-NMMA infusion (the L-NMMA group). The present findings suggest that NO synthesis may play a crucial role in the autoregulation of LCBF in response to a reduction in blood pressure in the cerebral cortices, cerebellar cortex and several deep brain regions. PMID- 8477050 TI - Muscarinic cholinoceptive reticular mechanisms and parabrachial neuron discharge: a novel experimental approach. AB - This study examined the hypothesis that cholinergic receptor mechanisms within the gigantocellular tegmental field (FTG) of the medial pontine reticular formation can cause state-dependent changes in the firing rates of parabrachial nuclear complex (PBNC) neurons. Using intact, unanesthetized cats, long-term recordings were obtained from single PBNC neurons following FTG administration of cholinergic agonists and antagonists. We show that the state-dependent decrease in PBNC cell discharge reported in this study can be attributed to muscarinic mechanisms within the FTG. Our pharmacological blocking results further suggest that diminished PBNC discharge was mediated by non-M1 muscarinic receptors in the FTG. This study demonstrates the usefulness of combining long-term neuronal recordings in the PBNC with multiple pharmacological manipulations within the FTG. PMID- 8477051 TI - Effect of streptozotocin-diabetes on the level of VIP mRNA in myenteric neurones. AB - The effect of streptozotocin-induced diabetes on the production of vasoactive intestinal polypeptide messenger RNA in the myenteric neurones of 8 weeks diabetic rat intestine was examined using in situ hybridization. Total ganglion cell number per length (mm) of tissue section was measured using NADH diaphorase histochemistry. Although ganglion cells were more numerous in the control preparations compared with diabetic samples, a significantly greater number of vasoactive intestinal polypeptide messenger RNA-containing cells was detected in the diabetic tissues. These observations suggest that there is either a decrease in the breakdown of vasoactive intestinal polypeptide messenger RNA or an increase in its synthesis in myenteric neurones of diabetic rat intestine. PMID- 8477052 TI - Ibogaine induces glial activation in parasagittal zones of the cerebellum. AB - Ibogaine, an indole alkaloid, has been proposed for treatment of drug addiction, yet its mechanism, site of action, and possible neurotoxicity have not been determined. Since neuronal injury is known to activate neurologlial cells, we investigated potential neurotoxic effects of this drug in rats by examining expression of specific glial markers. After treatment with ibogaine (100 mg kg-1 i.p.; 1-3 doses), we observed increased cytochemical markers in both microglia (OX-6, OX-42, W3/25) and astrocytes (GFAP), associated with striking morphologic changes in these cells. Activated glial cells were restricted to longitudinally oriented, parasagittal stripes within the vermis of cerebellar cortex. The ibogaine-induced activation of cerebellar glial cells is highly suggestive of neuronal degeneration, most likely of Purkinje cells. PMID- 8477053 TI - Interleukin-2 regulates monoamine and opioid peptide release from the hypothalamus. AB - The present study determined whether interleukin-2 (IL-2) and IL-2 receptors are present in the adult rat hypothalamus. In addition, we determined whether IL-2 is involved in the regulation of neurotransmitter release from hypothalamic slices. In the hypothalamus, the highest levels of endogenous IL-2 and IL-2 receptors were localized to the median eminence and arcuate nucleus. Application of exogenous IL-2 to hypothalamic slices produced significant decreases of potassium (25 mM)-evoked [3H]noradrenaline release (24%) without significantly affecting the evoked release of [14C]glutamate, [14C]5-hydroxytryptamine, [3H]dopamine or [3H] gamma-amino butyric acid. In addition, IL-2 increased the potassium-evoked release of methionine-enkephalin (by 78%) and beta-endorphin (by 38%) from hypothalamic slices without affecting the release of leucine-enkephalin. In contrast, the spontaneous release of neurotransmitters and neuropeptides was not affected by exogenous IL-2. Overall, the findings of this study suggest that hypothalamic IL-2 is an endogenous neurokine that may be of consequence to the regulation of hypothalamic function. PMID- 8477054 TI - MK-801 sensitizes rats to pilocarpine induced limbic seizures and status epilepticus. AB - High doses of pilocarpine are known to produce prolonged seizure activity in rats. Previous studies show that pretreatment with LiCl will sensitize rats to the convulsant effects of pilocarpine. Here we report that the anti-epileptogenic and anticonvulsant drug MK-801 (dizocilpine) paradoxically also sensitizes rats to pilocarpine induced limbic seizures and limbic status epilipticus (LSE). If rats were pretreated with MK-801, normally subconvulsive doses of pilocarpine rapidly produced LSE. LSE could be prevented by co-administration of either atropine or diazepam with MK-801. PMID- 8477055 TI - The cholinergic marker Chol-1 is selectively localized in nerve terminals. AB - The subcellular distribution of the cholinergic-specific gangliosidic Chol-1 antigens in rat brain has been compared with that of total ganglioside as a marker for neural plasma membranes, particle-bound choline acetyltransferase (ChAT) as a synaptosomal marker, and supernatant ChAT as a marker for neuronal perikaryal cytoplasm. Over 50% of brain Chol-1 was recovered in a synaptosome fraction prepared by a standard density-gradient method. The specific concentration of Chol-1 relative to protein or major gangliosides was also highest in the synaptosome fraction and low in a supernatant fraction which contained most of the neuronal plasma membrane fragments. ChAT was likewise mainly recovered in the synaptosome fraction but its relative concentration there was significantly less than that of Chol-1 (p < 0.01). PMID- 8477056 TI - Semantic process in kana word reading: activation studies with positron emission tomography. AB - Regional cerebral blood flow was measured by positron emission tomography to study changes during Japanese kana word or kana non-word reading tasks. The main cortical activation was observed bilaterally in the lateral and medial occipital gyri, and the left posterior inferior temporal area in both kana word and kana non-word tasks. In addition, the kana word task activated the right posterior inferior temporal area. Comparison of the mean regional cerebral blood flow increases revealed that the kana word task activated the left posterior inferior temporal area more than the kana non-word task, suggesting the role of the semantic process as well as the morphological one in this area. PMID- 8477057 TI - Opioid regulation of gonadotropin-releasing hormone gene expression in the male rat brain as studied by in situ hybridization. AB - It is well documented that gonadotropin-releasing hormone (GnRH) release is negatively regulated by opiates. In order to investigate the role of opiates in the regulation of GnRH gene expression in the rat brain, we studied the effects of chronic administration of the opioid drug morphine and an opiate receptor antagonist naloxone on GnRH mRNA levels as measured by in situ hybridization. Four-day treatment with morphine (40 mg kg day-2) produced a 44% decrease in the number of silver grains overlying GnRH neurones. Conversely, naloxone (4 mg kg day-2) also administered during 4 days increased by hybridization signal by 22%. The concomitant administration of morphine and naloxone completely prevented the effect of morphine on GnRH gene expression indicating the inhibitory influence of morphine is likely to be mediated by opioid receptors. The present data clearly indicate that opiates can inhibit not only the release of GnRH and consequently LH secretion but also the biosynthesis of the neuropeptide as evaluated by mRNA level measurements. PMID- 8477058 TI - Treatment of standard risk acute lymphoblastic leukemia in children with the Tokyo Children Cancer Study Group (TCCSG) L84-11 protocol in Japan. AB - During the period June 1984 through February 1989, 207 children, newly diagnosed with standard-risk acute lymphoblastic leukemia (ALL), were treated with the Tokyo Children Cancer Study Group L84-11 protocol. The patients were randomized into two regimen groups (S1 and S2). All patients received identical induction therapy with vincristine, prednisolone, and L-asparaginase. For central nervous system (CNS) prophylaxis, the patients in regimen S1 received cranial irradiation (18 Gy) and intrathecal chemotherapy starting at 5 weeks, while those in regimen S2 received this therapy starting at 24 weeks. Consolidation consisted of cyclic therapy with vincristine and dexamethasone, and then, after 128 weeks, with medium-dose methotrexate, CNS chemoprophylaxis, and dexamethasone. Regimen S2 employed early consolidation with three doses of medium-dose methotrexate and CNS chemoprophylaxis. The treatment duration was 3.5 years. Complete remission was achieved in 96.0% and 99.0% of the patients in regimens S1 and S2, respectively. Event-free survival (EFS) rates were 80.0 +/- 3.5% in total, 74.5 +/- 5.7% in regimen S1, and 85.1 +/- 5.7% in regimen S2 at a median follow-up of 42 months (< 85 months). There was no significant difference in the EFS between the two regimens. As compared with recently reported results of treatment for this disease, our protocol can yield similar EFS rates with mild toxicity. PMID- 8477059 TI - Re-analysis of prognosis in refractory anemia alone, with ring sideroblasts, and with excess of blasts. AB - Based on 473 primary cases of refractory anemia (RA), RA with ring sideroblasts (RARS), or with an excess of blasts (RAEB), new staging systems for overall survival, leukemic transformation, and nonleukemic death were developed. The reproducibility of these new staging systems, our former staging systems for leukemic transformation and nonleukemic death, and that for overall survival provided by Sanz et al. (Blood 1989;74:395-408), were estimated using a total of 132 patients with RA, RARS, or RAEB (test sample). The correlation of risk ratios of the test sample from our system and that of Sanz et al. was poor (tau = 0.24; Kendall rank correlation). Our risk ratio was a significant (p = 0.0012) continuous covariate of the Cox model life-table analysis in the test sample but that of Sanz et al. was not. The new and previous staging systems for leukemic transformation were highly similar (tau = 0.7) and risk ratios of both systems were significant in the test sample (p = 0.00046 and 0.0017, respectively). Based upon the new system, patients at high risk for leukemic transformation RA or RARS were identified as males, with bone marrow myeloblasts higher than 2.5%, abnormal granules in the granulocytes, and circulating erythroblasts. Their cumulative leukemic transformation rate exceeded 50% within 2 years from presentation. The new and previous systems for nonleukemic death were moderately correlated (tau = 0.47). The risk ratios of both systems were significant in the test sample (p = 0.00012 and 0.000024, respectively) but failed to stratify test sample patients into three distinct risk groups. In conclusion, our new staging systems for overall survival and leukemic transformation were reproducible in RA, RARS, or RAEB patients and will be useful especially in identifying high-risk patients with RA or RARS, who are considered to be at lower risk by the FAB classification. PMID- 8477060 TI - An infant with both autoimmune neutropenia and idiopathic thrombocytopenia with IgG2/IgA deficiency. AB - We report an infant with autoimmune neutropenia (AIN), idiopathic thrombocytopenia (ITP), and IgG2/IgA deficiency. The patient was referred to our hospital at 5 months of age because of epistaxis and generalized petechiae. Physical examination revealed moderate hepatosplenomegaly. A complete blood count revealed a platelet count of 2.0 x 10(3) cells/microliters, and a white cell count of 3,600 cells/microliters, with severe neutropenia (less than 1% bands and segmented cells). Neutrophils and platelets adhering to megakaryocytes were decreased in the bone marrow. Tests for serum neutrophil-binding IgG (NB-IgG) and platelet-associated IgG (PA-IgG) were positive. A diagnosis of both AIN and ITP was made and therapy with intact-type gamma-globulin and prednisolone was initiated. Improvement occurred, but was temporary. A lack of serum IgA and IgG2 was noted during the clinical course. The patient has not been susceptible to bacterial infections but has had a severe clinical course with rubella and chickenpox. PMID- 8477061 TI - MDR1 (multidrug resistance) gene expression in adult acute leukemia: correlations with blast phenotype. AB - Resistance to multiple chemotherapeutic agents is related to the production of P glycoprotein, a transmembrane drug efflux pump that is encoded by the multidrug resistance gene (MDR1). To detect low-level or heterogenous expression of the MDR1 gene in acute leukemia, we have developed sensitive, specific and semi quantitative protocols for measuring levels of MDR1 mRNA, based on the polymerase chain reaction. Using this assay, we screened blasts from 20 patients with untreated adult acute leukemia for evidence of MDR1 gene expression. The level of MDR1 mRNA was normalized to beta 2-microglobulin mRNA and was defined by reference to the highly resistant trimetrexate-selected leukemia cells MOLT 3/TMQ200 (1.80). MDR1 mRNA was observed in 14 out of 20 patients. Higher MDR1 mRNAs were observed in three patients with phenotypes of undifferentiated or minimally differentiated nonlymphocytic acute leukemia, as compared with other types of acute leukemia (0.98 vs. 0.25). In contrast, lower MDR1 mRNAs were found in five patients with acute promyelocytic leukemia, as compared with other types of acute leukemia (0.08 vs. 0.45). These findings suggest that MDR1 gene expression is correlated with the leucocyte differentiation stage of leukemia. MDR1 gene expression may, in part, explain the responsiveness to chemotherapy in these distinct subtypes of acute leukemia. PMID- 8477062 TI - Cutaneous granulocytic sarcoma at the exit site of Hickman indwelling venous catheter. AB - An unusual case of cutaneous granulocytic sarcoma (chloroma) developing at the exit site of a Hickman indwelling venous catheter in a patient with acute myelogenous leukemia (AML) is described. The possible role of the venous catheter in the development of this tumor at this unusual site is discussed. PMID- 8477063 TI - Macrophage colony-stimulating factor (M-CSF) enhances complement component C3 production by human monocytes/macrophages. AB - The third complement component, C3, is an important factor in the host defense mechanism in which monocytes/macrophages participate as the primary phagocytes. Monocytes/macrophages are the principal extrahepatic producers of C3, and this C3 production is thought to be regulated by several cytokines. In the present study, we demonstrated that human macrophage colony-stimulating factor (M-CSF) enhanced C3 production by human peripheral monocytes in serum-free culture. Analytical immunoblot and ELISA showed that the presence of M-CSF increased the production of intracellular pro-C3 and extracellular C3 for 24 h in a dose-dependent manner. To confirm the rapid effect of M-CSF on C3 production, we performed metabolic labeling of C3 with [35S]methionine. The production of [35S]C3 for the first 6 h in the presence of M-CSF was also increased as compared to that in the absence of M-CSF. In addition to the previously reported effects of M-CSF on monocytes/macrophages, such as the enhancement of C3 receptor expression and C3 receptor-mediated phagocytosis, we consider that the effects of M-CSF demonstrated in this study are of importance in the local immune system organization of C3 and monocytes/macrophages. PMID- 8477064 TI - A comparative study of CHOP versus MEVP (mitoxantrone, etoposide, vindesine, prednisolone) therapy for intermediate-grade and high-grade non-Hodgkin's lymphoma: a prospective randomized study. AB - To evaluate a new combination chemotherapy with mitoxantrone (MXT), etoposide (VP 16), vindesine (VDS), and prednisolone (MEVP therapy) as a front-line chemotherapy for non-Hodgkin's lymphoma (NHL), a prospective randomized study comparing this therapy (28 patients) with CHOP therapy (29 patients) was conducted in 57 patients with intermediate-grade or high-grade NHL with stages II IV. The MEVP therapy consisted of 10 mg/m2 of MXT intravenously on day 1, 2 mg/m2 of VDS intravenously on day 1, 200 mg/m2 of VP-16 orally on days 1-3, and 40 mg/m2 of prednisolone orally on days 1-5. This regimen was repeated every 3 weeks for up to 10 courses. Complete responses (CR) were achieved in 17 (63.0%) of the 27 evaluable patients treated with MEVP therapy, and in 20 (71.4%) of the 28 evaluable patients treated with CHOP therapy. Relapse-free survival rates and overall survival rates at 3 years were 58.8% and 46.4%, respectively, for the MEVP group and 70.0% and 54.0%, respectively, for the CHOP group. Granulocytopenia was more severer and associated infection episodes were more frequent in the MEVP group. MEVP therapy was effective as a front-line chemotherapy for intermediate- and high-grade NHL, although it was not superior to CHOP therapy in treatment effect and was not less toxic than CHOP. PMID- 8477065 TI - Ultrastructural analysis of a human megakaryocytic leukemia cell line (CMK11-5) in response to platelet agonists. AB - To further characterize the ultrastructure of the human megakaryocytic leukemia cell line, CMK, and its subclone CMK11-5, was observed. Stimulation with platelet agonists, ADP, thrombin, and collagen caused enlargement of vacuoles, projections of the cell surface, appearance of fibrous material in the enlarged vacuoles, and loss of alpha granules. We also found that horseradish peroxidase (HRP) incorporated into the granular structures of the cell could be transported out of the cell. The activation of CMK cells by platelet agonists indicates that human megakaryocytes may be activated in thrombotic states. CMK with particular megakaryocytic properties is a useful cell model for studying megakaryocytic function. PMID- 8477066 TI - An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-carboxyglutamic acid domain relevant to a thrombotic tendency. AB - Protein C Yonago is a dysfunctional protein C characterized by defective anticoagulant activity determined by a coagulation assay and normal amidolytic activity measured on a synthetic substrate S-2366 (Iijima et al., Thromb Res 1991;63:249-257). We have identified a single point mutation of C to G in codon 57 (CGG-->GGG) of the gene for protein C Yonago by genetic analysis utilizing the polymerase chain reaction. The mutation should have resulted in an amino acid substitution of Gly for Arg at position 15 of the light chain of mature protein C. No mutations were found in nucleotides spanning the putative gamma-carboxylase recognition site or gamma-carboxyglutamic acid residues of protein C. Protein C Yonago was non-reactive to monoclonal antibodies JTC-1 and -3 that solely recognized the calcium-dependent conformation of the gamma-carboxyglutamic acid domain. This indicated that the mutation had critically perturbed the highly conserved structure of the gamma-carboxyglutamic acid domain. Thus, the calcium dependent conformation required for the phospholipids binding to exert the physiological functions of protein C may not have been elicited normally in this abnormal protein C, resulting in defective generation of anticoagulant activities in plasma. Consequently, no anticoagulant activities may have been generated in vivo. PMID- 8477067 TI - [Signal characteristics of malignant and benign lesions in dynamic 2D-MRT of the breast]. AB - In a retrospective study of 400 dynamic MR examinations of the breast the signal/time ratio of 62 histopathologically correlated lesions (19 benign, 42 malignant) was evaluated. Points of evaluation were initial signal enhancement (1st and 2nd minute), post-initial signal appearance (2nd to 5th minute) and signal distribution (homogeneous, marginal). Based on these criteria, a point system was defined to help in the assessment of lesions in dynamic breast-MR imaging. The overall sensitivity of this method was 95.3%, the specificity to 89.5% and the accuracy to 93.5%. Pitfalls resulted in two cases of non-invasive carcinoma and in two patients with fibroadenoma. PMID- 8477068 TI - [MR tomographic functional analysis of the left ventricle]. AB - The following contribution presents a continuous MRT analysis of the contraction and relaxation processes of healthy left ventricles giving reference values for contraction and relaxation velocities. For the total ventricle we have Vsyst. r. total = 342 +/- 47% LVEDV/sec and Vdiast. r. total = 303 +/- 59% LVEDV/sec. In relation to the end-diastolic (tomographic) volume (EDSV) significantly greater changes in volume per unit of time were measured apically compared to basal (systolic: 411 +/- 89% EDSV/sec apical vs 261 +/- 35% EDSV/sec basal; diastolic: 810 +/- 145% EDSV/sec apical vs 245 +/- 70% EDSV/sec basal). Occurrence of the end-systolic minimal volumes of apical tomographic layers was delayed against the total ventricle by 22.4 +/- 7.9% t syst. Within the ventricle there was systolically a redistribution of the proportions of volume from apical to basal. PMID- 8477069 TI - [Detection of chronic recurrent pulmonary emboli using spiral-CT]. AB - Chronic recurrent pulmonary emboli may lead, in rare cases, to progressive pulmonary arterial hypertension which cannot be treated medically. These patients may be helped by bilateral pulmonary thrombendarterectomy. The value of spiral CT in the diagnosis of this condition was demonstrated in 31 patients. In 12 patients, thrombi could be shown to be the cause of the pulmonary arterial hypertension. Indirect criteria were vascular occlusions, changes in calibre and mural irregularities which were shown in varying degrees in all patients. In 22 of 31 patients there was non-homogeneity of perfusion with greater opacification of the perfused lung parenchyma. In 11 patients scars related to pleural surfaces were seen. Typical changes of right heart insufficiency (cardiomegaly, widened central pulmonary arteries) were shown in all patients by CT. PMID- 8477070 TI - [Invagination in adults]. AB - Intussusceptions in adults are rare. With the increasing use of sonography, CT and improved methods for examining the small bowel, they are now diagnosed more frequently before operation. If one considers the possibility, acute invaginations can be readily diagnosed by sonography or barium examination; the CT appearances are pathognomonic. In long-standing cases it may be difficult to separate the oedematous small bowel walls from each other. The "duck bill" narrowing is a sign of chronic invagination. PMID- 8477071 TI - A modified per os double contrast examination of the colon in the elderly. AB - A modified per os double contrast examination of the colon was used in 62 elderly patients in whom conventional barium enema had been unsuccessful. We created endogenous gas generation instead of air insufflation by per os administration of a special mixture containing barium sulfate, lactulose and gastrografin. Good quality double contrast images of the colon were obtained after 12 hours in 59 of the 62 patients. The sensitivity of the method was 100% in 6 patients suffering from carcinoma and in 15 patients suffering from diverticular disease. However, the method failed to demonstrate small solitary polyps in 5 patients and it was also negative in another 27 patients. 7 of these had negative endoscopy and in the remaining a definite diagnosis was not established by any other method. It seems that this method may become an alternative for investigation of suspected colonic pathology in the elderly patients with difficulty in retaining the barium enema. PMID- 8477072 TI - [Pancreatic metastases: sonographic and computed tomographic findings]. AB - We analysed sonographic (n = 19) and CT (n = 15) findings in 19 patients with intrapancreatic metastases (solitary: n = 8, multiple: n = 11) from solid tumours. The diagnosis was confirmed either histologically (n = 5) or by the follow-up showing decrease of the size of the lesion due to chemotherapy (n = 3) or progression without specific therapy (n = 11). Clinically or serologically organ-related symptoms were found in 5 cases, whereas the rest of the patients were free of symptoms. Sonographically the metastases appeared hypoechogeneic compared to normal pancreatic parenchyma. In 15 cases CT at the time of sonographic investigation demonstrated hypodense intrapancreatic lesions (8/15) or bulging of the organ contour without differences in density (2/15). In some patients (5/15) sonographically detected metastases measuring less than 2 cm were not discovered via CT. In a patient with known malignancy multiple intrapancreatic lesions must be considered as metastases. Differential diagnosis includes diffusely growing pancreatic carcinoma, haemorrhagic necrotising pancreatitis and focal infiltrates due to malignant lymphoma. PMID- 8477073 TI - [A liver tumor model in the rat suitable for experimental MRT]. AB - A malignant tumour was implanted in the livers of 205 rats in the context of an experimental MRT project. The implantation technique of the Novikoff hepatoma is described. Within 10 days of implantation a solitary one-centimetre intrahepatic tumour develops; it is a hypovascular tumour with an invasive periphery and central tumour necrosis. The tumour model is distinguished by a high success rate of 91.1% and is suitable for experimental MRT studies of liver tumours. PMID- 8477074 TI - [Magnetic resonance tomographic diagnosis of periarticular cystic space-occupying lesions in the knee joint]. AB - The MR images of the knee joint of 100 successively examined patients were evaluated in retrospect with regard to periarticular cystic lesions. There were 18 popliteal cysts, 8 meniscal cysts and 4 ganglion cysts. Localisation and internal structure of the lesions were of main importance in respect of differential diagnosis. All meniscal cysts were associated with horizontal meniscal tears. Spin-echo and 3D gradient-echo images did not enable differentiation because of signal intensity values. A spin-echo sequence with long repetition time in double-echo technique was best suited to assess the periarticular cystic lesions as well as the intraarticular pathological changes which were often concomitant. PMID- 8477075 TI - [Aneurysmal bone cyst or giant cell tumor. The value of x-ray diagnosis for differential diagnosis]. AB - Depending on analysis of radiographic morphology, location and patient's age of 72 aneurysmal bone cysts (ABC) and 47 giant cell tumours (GCT), the following criteria suggest an ABC with a high positive predictive value: location in the diaphysis (100%), in the shaft (92%), in the metaphysis or metadiaphysis (86%), patient younger than 17 years (97%) and growth rate grade Lodwick-IA (88%). GCT were selected via the following criteria: epimetaphyseal location (82%) and growth rate grade Lodwick-II (100%). In 14% of the cases, differential diagnosis between both entities is radiologically impossible. PMID- 8477076 TI - [Functional imaging of the brain using low dose gadolinium-DTPA and Turbo-FLASH sequences]. AB - A method for measuring regional blood volume and flow is described based on the reduced relaxation time following intravenous injection of Gd-DTPA. The optimal Gd dose and other parameters were first determined using turbo-flash sequences and a dilution phantom. A single maximum was found for a Gd-DTPA concentration of 4 mmol/l. Taking account of normal heart/time volumes and in order to stay below this arterial value Gd-DTPA was injected as a bolus at the rate of 1 mmol/sec. From the phantom measurements there appears to be a functional connection between measured signal intensity and Gd concentration. The method was applied to 15 patients with cerebral tumours, using altogether 26 perfusion examinations. The results from 4 patients are given as examples; in these, blood volume and flow were calculated for each pixel in a 128 x 128 matrix. It was found that the Gd DTPA injected is sufficient to be shown with certainty in the grey and white matter and that this is able to demonstrate pathological changes in a functional manner. Comparison with Gd-DTPA doses such as are used for morphological imaging (typically, 10 mmol corresponding to 0.1 mmol/kg body weight) has shown that doses above 1.6 mmol may lead to distortion of the concentration curves. PMID- 8477077 TI - [Dynamic cranial CT in ischemic cerebral lesions]. AB - 58 patients with recent transient or permanent neurologic deficits of with proven carotid stenoses were examined by dynamic CT at the level of the internal capsule. In the presence of cerebral infarcts there was marked delay in the time/density curve with reduced peaks. Abnormal perfusion could be demonstrated by early examinations before definite morphological changes were seen. With transient ischaemic attacks there were no significant changes in perfusion; in the presence of carotid stenoses the results were variable. The perfusion abnormalities in the hemispheres shown by dynamic cranial CT could be confirmed to some extent by 99mTc-HMPAO-SPECT. PMID- 8477078 TI - MRI of acoustic schwannoma: a retrospective study of 89 tumours. AB - Magnetic resonance imaging (MRI) is now considered the diagnostic study of choice for evaluation of patients with suspected acoustic schwannoma. This retrospective study of 118 MR examinations presents an analysis of the MR findings of 89 acoustic tumours in 86 patients. The method of examination included precontrast and gadolinium(Gd)-enhanced MRI in 72 and plain MRI in 14 patients. The common MR appearances of acoustic schwannomas were: on T1-weighted images (WI) isointense (36%) or slightly hypointense (64%) relative to the brainstem; intense and homogeneous contrast enhancement in 62%; the shape of the tumour was round or oval in 71%; the tumour was centred at/or located in the internal auditory canal (IAC) in 80%. The small acoustic schwannomas were mostly round or oval in shape and showed homogeneous signal intensity (SI) both before and after Gd. The larger acoustic tumours were more heterogeneous in morphology and SI. The significance of these and other signs, early diagnosis and differential diagnosis are discussed. PMID- 8477079 TI - [The importance of magnetic field strength in the MR diagnosis of multiple sclerosis: a comparison of 0.5 and 1.5 T]. AB - The value of magnetic resonance (MR) to establish the diagnosis of multiple sclerosis (MS) is well known. This study was undertaken to compare MR imaging of the brain of MS patients at high (1.5T) and mid (0.5T) field strength. 25 patients with MS underwent two consecutive MR studies within one hour, each consisting of axial proton density and T2-weighted spin-echo images. Lesions in the supratentorial white matter and corpus callosum and those in the brain stem and cerebellum were separately counted. At 1.5T significantly more lesions were seen than at 0.5T (p < 0.05). Although T2-weighted images at 1.5T added significant information compared to images obtained at 0.5T, in none of our 25 patients the diagnosis was missed at 0.5T. However, at 1.5T dissemination in space was better demonstrated, suggesting MR scanning with high field-units to be favourable in patients with clinically suspected MS. PMID- 8477080 TI - [Experiences in the use of video conferencing equipment in large auditoriums during clinical conferences]. PMID- 8477081 TI - [Erosion and bronchopleural fistula of an oleothorax caused by a TBC cavern]. PMID- 8477082 TI - [Subperiosteal osteoid osteoma--a rare cause of "unclear" wrist pain]. PMID- 8477083 TI - Olfactory neuroblastoma: radiological features. PMID- 8477084 TI - [Dissection of the vertebral artery. Demonstration in MRT]. PMID- 8477085 TI - [Doppler studies of soft tissues and bones. A new field for sonography?]. PMID- 8477086 TI - Age-related changes in the hemostatic system. AB - The increased incidence of arterial thromboembolism in the elderly has prompted investigation of age-related changes in the hemostatic system. Aging is associated with increased plasma levels of fibrinogen, factor VII and factor VIII, which have been shown to be risk factors for thrombotic disease in five large epidemiological studies. An increased responsiveness to different aggregating stimuli, elevated levels of beta-thromboglobulin and an increased production of thromboxane A2 were reported in the platelets of the elderly. These alterations are associated with modifications of platelet membrane lipid composition (namely an increase in the cholesterol/phospholipid ratio and a decrease in linoleic acid) with possible related changes in membrane fluidity. Moreover, a decrease in the number of platelet prostacyclin and thromboxane A2 receptors was observed with aging. Fibrinolytic activity is impaired in the elderly, probably due to an increase in plasminogen activator inhibitor 1. Interestingly, hypercoagulability has been demonstrated by an increase in the activation markers of the coagulation cascade (mainly fibrinopeptide A and prothrombin activation fragment F 1 + 2). Finally, clinical and experimental evidence suggests that endothelium could play a central role in hemostatic alterations which determine a thrombophilic state in the elderly. PMID- 8477087 TI - Clinical applications of immunoglobulin free light chain estimations. AB - The relevance of free light chain assays to diagnosis, staging, treatment and prognosis assessment in B-cell disorders (including myeloma, chronic lymphocytic leukaemia, and lymphoma), multiple sclerosis and diabetes is discussed and their actual and potential use is examined. PMID- 8477088 TI - Distribution of lecithin-cholesterol acyltransferase in normolipidemic and dyslipidemic plasma. AB - Plasma lecithin-cholesterol acyltransferase levels and cholesterol esterification rates have been reported to be different between normolipidemic and dyslipidemic subjects. Since apolipoprotein A-I is the presumed primary physiological activator of lecithin-cholesterol acyltransferase, the distribution of the enzyme among A-I-containing lipoprotein particles and A-I-free plasma in normolipidemic and dyslipidemic subjects was examined. A-I-containing lipoprotein particles with and without apolipoprotein A-II were isolated from plasma by immunoaffinity chromatography, and the lecithin-cholesterol acyltransferase mass in these particles and in the A-I-free plasma was quantified by radioimmunoassay. The plasma lecithin-cholesterol acyltransferase concentration was comparable between normolipidemic men (5.9 +/- 1.1 micrograms/ml, n = 15) and women (5.8 +/- 1.1 micrograms/ml, n = 19), with 71 +/- 8% located in particles without apolipoprotein A-II, 17.6 +/- 6% in particles containing A-II, and 12 +/- 6% in the A-I-free plasma. In patients with elevated cholesterol (n = 12), triglyceride (n = 10), and with renal failure (n = 15) plasma levels of the enzyme were significantly higher (6.7 +/- 1.2, 6.9 +/- 1.3, and 6.6 +/- 1.3 micrograms/ml, respectively) (P < 0.05). In all three patient groups, a higher proportion of the enzyme (27 +/- 12%, 33 +/- 12%, and 19 +/- 9%) was not apo A-I associated. This phenomenon was also observed in plasma samples after incubation at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477089 TI - Soluble interleukin-2 receptor in hairy-cell leukemia: a reliable marker of disease. AB - The CD25 molecule, which corresponds to the p55 alpha chain of the interleukin-2 receptor, is strongly expressed by neoplastic cells in hairy-cell leukemia and is released in large amounts in the soluble form which is detectable in serum. In order to assess the reliability of the soluble interleukin-2 receptor as a disease marker in the management of patients with hairy-cell leukemia, we investigated serum levels in 35 untreated patients and in 2 patients with the hairy-cell leukemia variant. In 21 of 35 patients soluble receptor levels were also monitored during and after recombinant interferon-alpha therapy. Clinical and hematological parameters were also assessed. Soluble interleukin-2 receptor levels were extremely high at the time of diagnosis in patients with typical hairy-cell leukemia [32,722 +/- 27,001 vs. 331 +/- 145 units/ml in controls (mean +/- SD)], but not in patients with the leukemia variant. A progressive decrease in soluble interleukin-2 receptor levels paralleled the clinical response to treatment, although normal values were never detected, even in patients who achieved an apparent complete remission. After recombinant interferon-alpha discontinuation, disease recurrence was accompanied by a progressive increase to pre-treatment soluble receptor levels. Overall, a close correlation was found between soluble interleukin-2 receptor values and total tumor burden (r = 0.84, P < 0.001). On the basis of these data, soluble interleukin-2 receptor should be regarded as a key marker in the management of patients with hairy-cell leukemia. PMID- 8477090 TI - Isotypes of human vaccinal antibodies to the Vi capsular polysaccharide of Salmonella typhi. AB - The immunoglobulin class and IgG subclass distribution of anti-Vi antibodies elicited by vaccination with a single injection of the purified polysaccharide or three injections of the inactivated whole cell typhoid vaccine was examined using an immunoenzymatic assay. The two vaccines induced antibody responses of similar magnitude and the predominant subclass of IgG antibodies was IgG1. PMID- 8477091 TI - Antibody-mediated neutropenia following bone marrow transplantation. AB - Unexpected neutropenia following allogeneic or autologous bone marrow transplantation may be caused by graft rejection, intrinsic stem cell failure, infection, graft-versus-host disease, relapse of the underlying neoplasm, or drug induced myelosuppression. Over the past decade an increasing number of reports have documented that the differential diagnosis also includes antibody-mediated neutropenia, a syndrome distinct from conventional graft rejection. In contrast to many of the other common causes of unexpected post-transplant neutropenia, antibody-mediated neutropenia usually responds well to treatment with corticosteroids, plasma exchange, intravenous immunoglobulin, splenectomy, or other similar measures. PMID- 8477093 TI - [Characteristics of day service center clients and their families based on their medical conditions]. AB - Clients utilizing day service centers in Hokkaido, and their families were surveyed for the purpose of analyzing present conditions of health, ADL level, family structure, motivation, activities, and changes in physical and psychosocial status. The average age of subjects was 76 years old with women generally being older than men. Most were living with their families. As to disease, cerebrovascular diseases were most common followed by hypertension and spinal-articulation diseases. Women had more hypertension problems compared to men who had more cerebrovascular conditions. Effectiveness of these day service programs were seen in the improvement of psychological functions. Persons with cerebrovascular disease had greater participation in functional rehabilitation training programs, and their ADL skills were improved. PMID- 8477092 TI - Serotonergic mechanisms are involved in the hemostatic action of erythropoietin in uremic patients. AB - Recombinant human erythropoietin was administered to 12 patients with end-stage renal failure on long-term hemodialysis. They responded to the therapy with a shortening of the prolonged bleeding time, starting from the 1st week of therapy, before a significant increase in hemoglobin concentration was achieved. We also observed an increase in the activity of tissue plasminogen activator and a decrease in the activity of its inhibitor. There were no changes in platelet count but a significant increase in blood and platelet serotonin concentration was found. The shortening of the prolonged bleeding time before the correction of the anemia correlated with the rise in blood and platelet serotonin concentration during erythropoietin therapy. We suggest the possible involvement of an serotonergic mechanism in the hemostatic action of recombinant human erythropoietin. PMID- 8477094 TI - [Effects of typhoon-caused power failure on medical care facilities]. AB - In the evening of September 27, Typhoon 19 passed Yamaguchi prefecture. The wind velocity exceeded anything that the local meteorological observatory has ever recorded so far in this area. When the typhoon was off shore near Yamaguchi prefecture, the gale brought down many electric-light poles around Hofu city with power failure in Hofu city continuing for more than a week. At the same time the total number of emergency patients in Hofu area was the most in the prefecture. Because the power failure continued for many days, there was more indirect damage attributable to this power failure than the damage related directly to the typhoon. The capacity of the emergency electric power generator equipment installed in the Central prefectural hospital in Hofu city is the largest in Yamaguchi prefecture. Even while electric power failed completely in the Hofu city area, treatment of most of the emergency patients at this hospital was possible. There is no hospital that has as large an electric generator as the Central hospital has. Had this typhoon hit in another area, the ensuring confusion which might have occurred at hospitals in that area would have put many patients in danger with the power failure in many hospitals. Power consumption needs in hospitals have increased over that expected on the time the hospital was built. Therefore, the electric power generators installed in hospitals are of the times very small and unable to cope with massive electrical outage. PMID- 8477095 TI - [A study on drinking and problem drinking in tuberculosis patients]. AB - Drinking and problem drinking were studied in 43 tuberculosis patients with the following results. The results of the KAST (Kurihama Alcoholism Screening Test) revealed that 10% of the patients were severe problem drinkers (diagnosed as alcohol dependent syndrome), 7% of the patients had drinking problems and 17% were potential problem drinkers. These percentages are higher than those of the general adult population. In the cases having higher KAST scores, the time between the onset of subjective symptoms and the first medical examination were long, but the time between the first medical examination and diagnosed tuberculosis was short. Severe tuberculosis patients showed higher KAST scores. It was assumed that tuberculosis patients who drink too heavily or are problem drinkers, were apt to put off consulting a physician, and as a result, the condition of tuberculosis would be more severe when they finally did see a physician. In the field of tuberculosis prevention and medical treatment, professionals should pay more attention to drinking and alcoholism. The need to stay sober is important in both preventing relapses and supporting recovery from tuberculosis. PMID- 8477096 TI - [Smoking habit of health professionals]. PMID- 8477097 TI - [An analysis of community mental health services at public health centers in the Tokyo metropolitan area--services for 727 new cases during 5 years in Bunkyo Ward]. AB - For an overview of the community mental health services at Public Health Centers (PHCs), cases were statistically analyzed from the aspect of 3 points: the situation of psychiatric treatment at initial contact (psychiatric treatment), the person who had been living with the case at first contact (living style) and the person who contacted the PHC first (first contact person). During approximately 5 years, 463 new cases contacted the 2 PHCs in Bunkyo-Ward for consultation. Among them, 132 were under psychiatric treatment, 324 under no treatment and 7 unknown. Additionally, 264 were found to be registered on official documents, some of whom received PHC services after being listed. The percentage of schizophrenic cases in the psychiatric treatment group at first contact were higher than in the non-treatment group. More cases with psychiatric treatment were visited by PHN than without treatment. There were great differences in the first contact person among the groups classified according to living style. Especially, in the non psychiatric group, the percentage of the first contact person being other than family and relative was higher in the group who had been living alone than any other groups. Percentages of personal interview of a case, consultation by a psychiatrist in PHCs, and visiting the home of a case were different among the groups classified by psychiatric treatment, living style and first contact person. However, no difference in services outcome (total number of contacts made by a cases, relatives of cases, and other related persons), or present service utilization (continuing, discontinued, completed) among the groups classified by psychiatric treatment, living style, and first contact person was seen. PMID- 8477098 TI - [Depressive states and their correlates in elderly people living in a rural community]. AB - In order to determine the prevalence of depressive symptomatology among the elderly in Japan, and examine relevant factor, a comprehensive survey was conducted. Subjects were 695 men and women aged 65 years and over in a rural village of Akita Prefecture. The Japanese version of the 20-item Center for Epidemiologic Studies Depression Scale (CES-D) was used as the measure of depressive symptomatology. The main results were as follows: 1. The score distribution was skewed to the right, more so than those in preceding studies from the United States. The prevalence of depression according to a CES-D cut point of 16 or greater was 5.3%. Neither age nor sex differences in prevalence were found. 2. Risk factors for circulatory disease such as blood pressure, ECG findings, chest X-P and blood components were not found to be related to CES-D score. Only the eye-ground change according to the Scheie's S classification was directly and significantly related to depression. 3. Those who had been treated for stroke over a year prior to the survey tended to have higher CES-D scores. Neither history of hypertension nor heart disease was associated with CES-D score. 4. Depression was more common among those who had experienced admission to hospitals over a year prior to the survey or who had suffered from hearing impairment or visual impairment. Low activities of daily living directly and significantly affected CES-D scores. PMID- 8477099 TI - [An epidemiological study of allergic conjunctivitis]. AB - An epidemiological study focusing on the home environment and lifestyle was conducted in order to analyze the differences between a group of patients with allergic conjunctivitis only and a group with other allergic diseases associated with allergic conjunctivitis. Subjects were five hundred and sixty-four patients who visited the Ophthalmologic Clinic of Tokai University Hospital during 1990, and for controls 200 households were randomly selected from an elementary school list in Yokohama city. RAST score was measured in 102 patients. A mailed questionnaire was sent to 240 patients chosen at random and to 200 controls. Sixty patients and 139 controls responded to the questionnaire. RAST score showed no statistical difference between patients with allergic conjunctivitis only and patients with other allergic diseases associated with allergic conjunctivitis. Analysis of associations between RAST score and seasonal symptoms, showed very strong positive reactions to pollens in patients with seasonal symptoms. On the other hand, in patients with constant symptoms during the year, reaction was very strong to house dust and mite. Epidemiological factors causally associated with allergic conjunctivitis were compared among the controls, patients with allergic conjunctivitis only (Group I), patients with other allergic diseases (Group II) and all patients (Group III). Compared to controls, Groups II and III had significantly higher prevalence of past history of skin itching and inflammatory symptoms (p < 0.05 and p < 0.01, respectively). Group II subjects showed more frequent use of carpets, when compared to the controls (p < 0.05). The use of Japanese mattress (futon) was more frequent in Group II and III than controls (p < 0.05 for both comparisons).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477100 TI - The prisoner's prisoner: the theme of voluntary imprisonment in the staff of correctional facilities. AB - The staff of correctional facilities voluntarily work in prisons. It seems plausible that the professionals, officers, and administrators engaged in such employment may have unconscious feelings of a desire or need for punishment. This topic does, in fact, appear common in the jokes and casual conversation in such facilities, perhaps indicating such an underlying theme. Indeed, those employees who were willing to discuss their experience in more depth corroborated the hypothesis. A sense of a need or desire for punishment in a staff's members may profoundly affect the prisoner's transference with the staff, and the staff's countertransference. These feelings may affect the many important decisions of correctional and clinical staff in prisons and related settings. PMID- 8477101 TI - Rule-Out and Rule-In scales for the M test for malingering: a cross-validation. AB - Previous research found the M test to have limited utility for the screening of malingering. Subsequently, Rogers et al. attempted to improve the test's discriminative ability by developing an alternative scoring procedure-Rule-In and Rule-Out scales. These scales showed promising results as a brief screener for malingering with hit rates as high as 95 percent. The present study cross validated their proposed decision rules, but found lower rates of classification accuracy. The most conservative decision rule (i.e., to maximize detection of malingerers) only identified 72.7 percent of the malingerers with a false positive rate of 50.8 percent. PMID- 8477102 TI - The validity of the M test in a residential forensic facility. AB - The validity of the M Test as a screening measure for malingering was assessed in a residential forensic treatment center. Clinically, malingering was recognized by the treatment staff as a significant problem among incompetent to proceed (ITP) defendants in this setting. A total of 79 ITP defendants completed the M Test under standard instructions. To assess the predictive validity of the M Test, its sensitivity and specificity were determined using three separate measures of malingering status. Using the original scoring procedure, the results provided estimates of sensitivity of 11, 31, and 29 percent and estimates of specificity of 67, 70, and 69 percent, respectively, for the three malingering status measures. A revised scoring procedure improved the sensitivity estimates to the statistically significant level of 86 percent for the malingering status measure that was defined as feigned or grossly exaggerated psychotic symptoms. The pattern of correlations between the M Test scales and a variety of other clinical measures suggested that, in this forensic treatment setting, the subject's pattern of responses to the M Test was primarily determined by the severity of cognitive impairment of that subject. PMID- 8477103 TI - Post-traumatic stress disorder and the law: critical review of the new frontier. AB - Since its debut in the psychiatric nomenclature in 1980, post-traumatic stress disorder (PTSD) has had a dramatic impact on criminal and civil jurisprudence. PTSD has created a cottage industry among both criminal and negligence attorneys and mental health practitioners. The diagnosis first achieved public notoriety when it was introduced as a new basis for the insanity defense. More recently "syndrome evidence" of the subtypes and variations of PTSD have encroached on the substantive criminal law of self-defense. In addition, the diagnosis may have an impact on such traditionally legal and factual determinations as the credibility of witnesses and may undermine conservative tort doctrine that attempts to cabin psychic injury. The emerging legal area of victims' rights has been strengthened and paradoxically divided by PTSD. Yet the newly defined disorder of PTSD has not borne such a heavy forensic burden easily. Indeed the diagnosis poses for psychiatry some of the very problems it supposedly solves for legal purposes, including the illusory objectivity of the causative traumatic event and the expert's dependence upon the victim's subjective and unverifiable reports of symptomatology for the diagnosis. PMID- 8477104 TI - Psychophysiologic testing for post-traumatic stress disorder: forensic psychiatric application. AB - The validity of the post-traumatic stress disorder (PTSD) diagnosis is limited by both the illusory objectivity of the traumatic event and the subjectivity of the ensuing syndrome. These limitations are especially problematic in the forensic setting. Psychophysiologic measurements may strengthen PTSD's forensic value by offering a more objective assessment technique for cases that find their way into the courtroom. Based upon the results of published research studies conducted in a range of military and civilian, PTSD and non-PTSD subjects, psychophysiologic data can provide evidence helping to establish or refute the presence of the DSM III-R PTSD arousal criteria, as well as aid psychiatric experts in estimating the probability of the disorder's presence in a given claimant. Psychophysiologic testing should be viewed as one component of a multimethod forensic psychiatric evaluation for PTSD. It is likely that it will soon be offered and, given current legal standards, admitted as evidence in civil and criminal litigation. PMID- 8477105 TI - An agenda for quality improvement in forensic mental health consultation. AB - Recent developments in quality assurance in health care have embraced the total quality management approach to industrial quality control. Setting a goal of "continuous quality improvement" for medical care, this approach features special attention to the process and systems of care provision. Applying this approach to the specialty of forensic mental health consultation yields a variety of potential ways of improving care, by articulating common problems in the consultation process that might respond to the total quality management approach. These problems include the setting of appropriate goals for forensic evaluation, and selecting cases for attention on the basis of those goals; determining appropriate standards for thoroughness and validity in the use of evaluation techniques; and establishing clear expectations regarding the provision of mental health services beyond the consultation process itself. Creating interdisciplinary teams at various levels of administration of trial courts and mental health agencies can provide contexts for reviewing cases, with the aim of discovering problems in these areas, educating professionals across boundaries about sources of problems, and developing clearer and more consistent standards of practice to reduce problems and improve quality of service. PMID- 8477106 TI - Appropriate short-term risk in psychiatry and the law. AB - Effective treatment decisions sometimes require substantial risk of short-term harm, which can be shown after-the-fact to have been preventable, thereby carrying some liability risk. To err on the side of short-term comfort or safety, however, may greatly increase the overall and long-term risks. For instance, to intrusively restrain a borderline patient from threatened acting out, may (1) fuel a regressive cycle that heightens future risk, (2) deprive the clinician of therapeutic leverage, and/or (3) so disrupt the treatment system that other patients unnecessarily suffer. Long-term thinking is not always convincing to judge or juror, because of less direct causal connections; hence, there is pressing need to develop rational criteria for when it should hold sway. Two competing trends of legal doctrine are relevant: risk-benefit analysis (utilitarian) and absolute values (absolutist). Presumptions of appropriate short term risk separately weigh five relevant factors, in interaction with one another: imminent safety, long-term risk, voluntariness of other agent, therapeutic boundaries, and social values. Forensic psychiatrists are advised to take a stronger stand in support of short-term risk, when needed to enhance long term safety and optimal standards of care. PMID- 8477107 TI - Multiple personality disorder: scientific and medicolegal issues. AB - Despite the intense study it has received since its inclusion in DSM-III, multiple personality disorder (MPD) largely remains an unvalidated construct. Definitional problems remain (there is not even agreement in the field as to whether a diagnosis of MPD truly means the existence of more than one personality), while the vagueness and liberality of existing criteria give the clinician little guidance in diagnosis. In forensic settings, diagnosis of MPD is even more problematic, since there is substantial evidence that the disorder cannot currently be phenomenologically distinguished from malingering. It also remains to be demonstrated that evaluators can determine whether alter personalities, if they exist, are truly unaware of each other, lack control over other alters' behavior, or are unable to know right from wrong. PMID- 8477108 TI - Indochinese patients in the civil commitment process. AB - This paper examines in detail the involvement of a group of Indochinese patients in the Oregon Civil Commitment process in the calendar years of 1985 and 1986. The authors found that there was no apparent difference in the rate of commitment as contrasted to the overall commitment rate of the general population. The results also indicated that there was heavy reliance on the Indochinese Psychiatric Program and staff to divert the involuntary Indochinese patients out of the commitment process. Furthermore, comparing the involuntary Indochinese patients to a randomly selected cohort of Indochinese patients hospitalized in the same period revealed no differences in demographic data, diagnosis, and treatment history except that the involuntary group was significantly younger and predominantly male. Finally, the follow-up study of the two cohorts showed high rates of hospitalization, noncompliance, and treatment drop-out. PMID- 8477109 TI - Excluding personality disorders from the insanity defense--a follow-up study. AB - Examining the effects of Oregon's statutory reform excluding personality disordered individuals from the insanity defense, we previously identified a study sample of insanity acquittees, each of whom was given a primary diagnosis of a personality disorder during subsequent evaluation at the state hospital. In the present study we explore the relationship between that diagnosis and the pretrial psychiatric diagnosis presented to the trial court. By reading the forensic mental health evaluations used at trial we found that 50 percent of our study sample of 34 personality disordered patients were diagnosed with psychotic disorders, affective disorders, retardation, and organic brain disorders. In addition to investigating the diagnosis offered as evidence at trial, we performed assessments of 38 mental health reports using published standards for forensic evaluation reports. We found compliance rates in the various categories ranged from 8 to 84 percent with a mean of 45 percent. We question the value of the mental health input to these trials, and believe that the data tend to validate past aspersions of forensic practice. PMID- 8477110 TI - Surgery for acid suppression in the 1990s. PMID- 8477111 TI - Acid suppression and the gastric flora. PMID- 8477112 TI - Postmarketing surveillance and the examination of the long-term safety of antiulcer drugs. PMID- 8477113 TI - Single-dose effect of enteric-coated aspirin on platelet function and thromboxane generation in middle-aged men. AB - OBJECTIVE: To evaluate the effect of a single dose of enteric-coated aspirin (ECA) in three different dosages on platelet function and thromboxane generation in middle-aged men. DESIGN AND METHODS: In a nonblind, nonplacebo-controlled, crossover study, a single dose of ECA (50, 250, or 1000 mg) was given in a tablet form to a group of healthy, middle-aged men. Ten subjects, aged 50-67 years, volunteered to participate in this study. Platelet functions including bleeding time, platelet aggregation, adenine nucleotides, beta-thromboglobulin, platelet factor 4, thromboxane generation, and aspirin measurement were determined. RESULTS: Before ECA ingestion, the intracellular adenine nucleotides (adenosine triphosphate, adenosine diphosphate) were decreased, and both beta thromboglobulin and platelet factor 4 were increased. These observations suggested that platelets were activated in vivo in middle-aged men. These findings returned to normal within 8 hours after the ingestion of ECA, and maintained normal for at least two days. Bleeding time was significantly prolonged at 8 and 24 hours compared with that before ingestion of ECA 1000 mg (p < 0.05). The generation of platelet thromboxane was maximally inhibited by approximately 40 percent in the samples 8 hours after ECA ingestion. Abnormal values of adenine nucleotides, beta-thromboglobulin, and platelet factor 4 returned to normal within 8 hours. Arachidonic acid-induced platelet aggregation was inhibited compared with that before treatment (p < 0.01) and the inhibitory effect was maintained for at least three days. Adenosine diphosphate- and epinephrine-induced aggregations were less inhibited than those induced by arachidonic acid. Inhibitory effects of ECA on platelet aggregation were dose dependent. CONCLUSIONS: Our study indicates that platelets are activated in middle-aged men and that a single dose of ECA 50 mg is safe and can inhibit thromboxane synthesis and platelet aggregation. These results suggest that a daily dose of ECA 50 mg may be useful for blocking platelet activation and preventing thrombosis. PMID- 8477114 TI - Subcutaneous absorption kinetics of two highly concentrated preparations of recombinant human growth hormone. AB - OBJECTIVE: The relative bioavailability of two highly concentrated (12 IU/ml) formulations of biosynthetic human growth hormone (GH) administered subcutaneously was compared. DESIGN: A randomized, crossover study. Conventional GH therapy was withdrawn 72 hours before each study period. There was a washout period of at least four weeks between the study periods. SETTING: Participants were recruited from an outpatient clinic and were hospitalized during the two study periods. PATIENTS: Fourteen GH-deficient patients (mean age 25.2 y, range 14-54). One patient was excluded from data analysis because of signs of endogenous GH secretion. INTERVENTIONS: At the start of each study period, GH 3 IU/m2 was injected subcutaneously. The two formulations, PenFill and PenSet, differ in the buffers used and in the relative content of mannitol and glycine. Serum profiles of GH were monitored frequently for 24 hours. Samples were taken every 30 minutes for 6 hours and then hourly. MAIN OUTCOME MEASURES: Bioavailability (F) and absorption dynamics of human GH were measured. The relative absorption fractions estimated from the areas under the individual serum concentration curves from 0 to 24 hours, and the observed time (Tmax) to reach the maximum concentration (Cmax) were determined. Short-term metabolic effects of GH on insulin-like growth factor (IGF-I), glucose, and insulin were determined. RESULTS: The geometric mean (SD) of F was 0.910 (1,236). The 90 percent confidence interval was 0.819-1.010. Mean (+/- SD) of Cmax was 12.65 +/- 5.89 and 12.58 +/- 4.40 ng/mL for PenFill and PenSet, respectively. Corresponding values for Tmax were 5.49 +/- 1.55 and 5.89 +/- 1.79 hours for PenFill and PenSet, respectively. There was a considerable interindividual variation, but the relative absorption fraction did not significantly differ from 1 (p = 0.13). Neither Cmax (p = 0.74) nor Tmax (p = 0.58) of the two formulations was significantly different. Injection of the two formulations induced similar increments in serum IFG-I (p = 0.48). Serum insulin and blood glucose concentrations were not significantly different. CONCLUSIONS: There is no significant difference between the absorption kinetics and short-term metabolic effects of these two highly concentrated formulations of biosynthetic GH. The two formulations are bioequivalent. PMID- 8477115 TI - Stability of famotidine in polyvinyl chloride minibags and polypropylene syringes and compatibility of famotidine with selected drugs. AB - OBJECTIVE: (1) to determine the stability of famotidine 200 micrograms/mL in admixtures with dextrose 5% injection (D5W) and NaCl 0.9% injection (NS) in polyvinyl chloride (PVC) minibags and polypropylene syringes, at room temperature (22 degrees C), protected and unprotected from light for 15 days; and (2) to evaluate the visual compatibility of famotidine with 34 selected drugs for four hours at room temperature. DESIGN: Concentration of famotidine samples was determined on day 0 and again on days 3, 6, 9, 12, and 15 by a stability indicating HPLC. Inspection for visual and pH changes was also performed at these time intervals. RESULTS: More than 95 percent of the day 0 famotidine concentration remained in all samples over the 15-day study period. During this period, all samples remained clear and colorless and no change in absorbance at 450 and 540 nm was observed. The pH of the samples also remained unchanged. Famotidine 2000 micrograms/mL was found to be compatible with 33 selected drugs; only furosemide was found to be incompatible. A white precipitate was observed when an equal volume of famotidine 2000 micrograms/mL in NS was mixed with furosemide 3000 micrograms/mL in D5W. The concentration of famotidine in the supernatant gradually decreased during the 4-hour study period. At 0.5, 1.0, 2.0, and 4.0 hours after mixture of famotidine with furosemide, famotidine concentrations were 97.5, 23.6, 21.7, and 17.2 percent of the initial famotidine concentration, respectively. CONCLUSIONS: Our results show that famotidine 200 micrograms/mL was stable in admixture with D5W and NS in PVC minibags and polypropylene syringes when these solutions were stored at room temperature, protected and unprotected from light for 15 days. Famotidine 2000 micrograms/mL in NS was compatible with 33 of the drugs, and was incompatible with furosemide. PMID- 8477116 TI - Fluconazole-cyclosporine interaction: a dose-dependent effect? AB - OBJECTIVE: To present cases supporting the hypothesis that fluconazole inhibition of cyclosporine metabolism is dose-dependent. DESIGN: Case reports. PATIENTS AND INTERVENTIONS: One renal-pancreatic transplant patient taking fluconazole 100 and 300 mg/d for 37 and 17 days, respectively; four bone marrow transplant recipients taking fluconazole 100 mg/d as antifungal prophylaxis and five other concurrent nonmatched recipients whose antifungal prophylactic agent is nystatin mouthwash. All of these patients underwent transplantation during the same period. RESULTS: There was a sharp rise in cyclosporine trough concentration (ng/mL), concentration:dose ratio (ng.mL-1/mg.kg-1), and serum creatinine concentration (mumol/L) in the renal-pancreatic transplantation patient taking fluconazole 300 mg/d. No such increase occurred at 100 mg/d. No significant alterations in cyclosporine concentration:dose ratio were seen in the patients undergoing bone marrow transplantation and receiving fluconazole 100 mg/d. CONCLUSIONS: The case of the renal-pancreatic transplantation patient shows a characteristic interaction profile, and it supports the hypothesis of a dose-dependent interaction between cyclosporine and fluconazole. Given the nephrotoxic potential of the immunosuppressant drug, dosage reduction and closer monitoring of cyclosporine concentrations and/or renal function in patients receiving fluconazole dosages greater than 200 mg/d must be considered. PMID- 8477117 TI - Excretion of bupropion in breast milk. AB - OBJECTIVE: To measure the excretion of bupropion and its metabolites in breast milk. A secondary objective was to determine whether the drug accumulated in the nursing infant. CASE SUMMARY: Milk and plasma samples were collected from a woman taking bupropion 300 mg/d in divided doses who was breastfeeding her 14-month-old son. A single plasma sample was collected from the infant. RESULTS: After a 100 mg dose, the peak bupropion breast milk concentration measured at two hours was 0.189 micrograms/mL. Milk-to-plasma ratios ranged from 2.51 to 8.58 over a six hour interval. Two of three metabolites also were measured in milk. Bupropion and its metabolites were not detected in the single plasma sample obtained from the infant. CONCLUSIONS: Bupropion accumulates in human breast milk in concentrations much higher than in maternal plasma. Two metabolites are also excreted into the milk. Neither bupropion nor its metabolites were detected in the infant's plasma, indicating that accumulation did not occur in this infant. PMID- 8477118 TI - Possible case of procainamide-induced intrahepatic cholestatic jaundice. AB - OBJECTIVE: To describe a possible case of procainamide-induced intrahepatic cholestatic jaundice that was recognized six weeks after the initiation of procainamide therapy and to summarize the five previously reported cases. CASE SUMMARY: A 77-year-old woman with a history of hypertension, insulin-dependent diabetes mellitus, temporal arteritis, and Wolff-Parkinson-White syndrome who had taken procainamide for six weeks presented to the hospital with disorientation and acute renal and hepatic dysfunction. In addition to disorientation, scleral icterus, and diffuse maculopapular rash, her physical examination was generally normal. There was no evidence of fever, nausea, vomiting, lymphadenopathy, or eosinophilia. Her liver enzyme concentrations increased significantly from baseline (beginning of procainamide therapy). Her N-acetylprocainamide (NAPA) concentration was elevated to 52 mg/L upon admission. Procainamide was discontinued and her NAPA concentration returned to within normal limits in two days. Diagnostic tests were performed to rule out active hepatitis, vasculitis, and liver malignancies. After procainamide was discontinued and prednisone treatment was started, she became more oriented and her liver enzyme concentrations slowly improved. DISCUSSION: Only five cases of procainamide induced liver abnormalities have been previously reported; these included granulomatous hepatitis and intrahepatic cholestasis. The mechanism for liver dysfunction is not known; however, it is proposed to be a delayed hypersensitivity reaction. Clinical hallmarks of hypersensitivity include fever, eosinophilia, rash, and lymphadenopathy; nausea and vomiting also may be present. Of the five reported cases, all experienced fever and only one experienced pruritus. No patients had eosinophilia or lymphadenopathy. Because of the temporal increase in liver enzyme concentrations after six weeks of procainamide therapy, we believe that this case represents another possible procainamide induced hypersensitivity reaction. CONCLUSIONS: Procainamide-induced liver dysfunction can occur from one day to six weeks after initiation of the drug and may subside one day to several weeks after discontinuation of therapy. Symptoms may include nausea, vomiting, rash, and fever. Liver enzyme concentrations are abnormal. It is important to recognize the possibility of such a reaction early so that procainamide therapy can be discontinued promptly to avoid further liver damage. PMID- 8477119 TI - Hepatotoxicity associated with cisplatin chemotherapy. AB - OBJECTIVE: To report a case of possible cisplatin-associated hepatotoxicity. CASE SUMMARY: A 69-year-old man received three cycles of cisplatin (100 mg/m2) and fluorouracil (1000 mg/m2/d for five days) for management of squamous cell carcinoma of the head and neck. Liver enzyme concentrations were within normal limits prior to each cycle of therapy but the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase concentrations increased on the second day of each cycle. The concentrations began to decline on day 3 of each course, despite continued fluorouracil administration, and returned to normal by day 10. The patient's antiemetic therapy included metoclopramide in cycle 1 and ondansetron in cycles 2 and 3, which may have contributed to the enzyme elevations. DISCUSSION: Case reports of cisplatin-associated hepatotoxicity are reviewed. An association between cisplatin administration and hepatotoxicity is proposed in this patient. CONCLUSIONS: This patient may have experienced cisplatin-induced liver damage. Metoclopramide and ondansetron may have contributed to this effect. PMID- 8477120 TI - Prevalence and descriptors of aspirin use as an antiplatelet agent in two New England communities. AB - OBJECTIVE: To determine the overall prevalence of aspirin use as an antiplatelet agent in a population-based sample of respondents between the ages of 18 and 64 years, and to describe their sociodemographic characteristics. DESIGN: Data were derived from five biennial cross-sectional household surveys conducted between 1981 and 1990 in two southeastern New England communities by the Pawtucket Heart Health Program. Individuals reporting aspirin use as an antiplatelet agent were identified using data from a structured medication interview. RESULTS: The prevalence of aspirin use per 1000 population was 2.5 (95 percent confidence interval [CI] 0.5, 4.4), 5.0 (95 percent CI 2.4, 7.6), 7.8 (95 percent CI 4.6, 11.0), 7.5 (95 percent CI 4.3, 10.6), and 11.8 (95 percent CI 7.1, 16.5) in the first through the fifth survey periods, respectively (p = 0.0002). The prevalence of aspirin use per 1000 men increased from 4.9 (95 percent CI 0.6, 9.1), 8.7 (95 percent CI 3.3, 14.1), 12.3 (95 percent CI 6.1, 18.5), 8.5 (95 percent CI 3.5, 13.5) to 23.2 (95 percent CI 13.4, 32.9) for the first through the fifth survey periods, respectively. The corresponding prevalence rates of aspirin use per 1000 women were 0.7 (95 percent CI 0, 2.1), 2.43 (95 percent CI 0.05, 4.80), 4.6 (95 percent CI 1.4, 7.8), 6.6 (95 percent CI 2.7, 10.6), and 2.7 (95 percent CI 0, 5.7). Both a gender trend (p = 0.0002) and a survey trend (p = 0.0001) were detected. A gender-survey interaction was not found. CONCLUSIONS: In this population, aspirin use was reported primarily by middle-aged men who had coexisting cardiovascular disease as indicated by concurrent medications. Aspirin use as antiplatelet therapy increased in the population-based samples of two New England communities over the past nine years, with slightly more than one percent of the respondents reporting its use in the fifth cross-sectional survey conducted in 1989-1990. This finding may reflect the publication of important clinical trials near the time the survey was performed and subsequent dissemination of the findings both in the professional and lay press. PMID- 8477122 TI - Naloxone and dementia. PMID- 8477121 TI - Reversible seizures and mental status changes in a dialysis patient on isoniazid preventive therapy. AB - OBJECTIVE: To report a case of reversible seizures and mental status changes in a dialysis patient given preventive isoniazid therapy. CASE SUMMARY: A 66-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) was given isoniazid prophylaxis following a purified protein derivative (PPD) reaction greater than 20 mm in duration. Oral administration of isoniazid 300 mg/d was started and four days later she was admitted to the hospital for confusion, lethargy, and focal seizures that began 24 hours after initiation of therapy. All medications were discontinued with the exception of oral pyridoxine 50 mg/d. Dialysis was withheld to determine if the seizures were medication induced rather than uremia related. Seizures and mental status changes were reversed with pyridoxine. Dialysis was restarted after the symptoms resolved. CONCLUSIONS: Preventive therapy against tuberculosis with isoniazid should be stressed throughout the medical community. Isoniazid has adverse effects including hepatitis and peripheral neuropathy (common) and convulsions (rare). Our experience suggests that additional supplementation with pyridoxine 50 mg/d should be given routinely to prevent adverse reactions in uremic patients. PMID- 8477123 TI - Medroxyprogesterone in osteoporosis. PMID- 8477124 TI - Nabumetone: a "nonacidic" nonsteroidal antiinflammatory drug. AB - OBJECTIVE: To review the pharmacology, pharmacokinetic disposition, dosage recommendations, adverse effects, drug interactions, and efficacy of nabumetone in patients with selected rheumatic disorders and soft-tissue injuries. DATA SOURCES: Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: antiinflammatory agents, nonsteroidal, nabumetone, rheumatoid arthritis (RA), and osteoarthritis (OA). Studies evaluating nabumetone reported in articles, abstracts, or proceedings involving human subjects were considered for inclusion. STUDY SELECTION: Special consideration was given to clinical studies using double-blind, randomized, parallel, controlled designs. Studies comparing the effectiveness and safety of nabumetone with placebo and other nonsteroidal antiinflammatory drugs (NSAIDs) were included. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed according to study design, sample size, and description of outcomes. DATA SYNTHESIS: Nabumetone is a nonacidic prodrug that is metabolized to an active nonsteroidal antiinflammatory moiety, 6-methoxy-2-naphthylacetic acid (6 MNA). 6-MNA is a structural analog of naproxen. Like naproxen and other NSAIDs, 6 MNA possesses analgesic, antipyretic, and antiinflammatory activity, 6-MNA has a prolonged elimination half-life, ranging from 17 to 74 hours, which allows for once-daily dosing. The efficacy of nabumetone for treating symptoms of RA and OA has been established in controlled clinical trials. Nabumetone also has been studied in ankylosing spondylitis and soft-tissue injuries. Adverse effects associated with nabumetone are similar to those associated with other NSAIDs. Gastrointestinal reactions occur most frequently in the form of abdominal pain or indigestion, nausea, or vomiting. Central nervous system adverse effects occur less frequently, and are followed in order of occurrence by rashes. CONCLUSIONS: Nabumetone is a prodrug metabolized to an active metabolite structurally related to naproxen. Studies have demonstrated the efficacy of nabumetone, but no advantages over the many other NSAIDs now available. PMID- 8477125 TI - Cetirizine: a new, nonsedating antihistamine. AB - OBJECTIVE: To introduce cetirizine, a nonsedating antihistamine, and discuss its mechanism of action, chemistry, clinical and comparative trials, and adverse effects. DATA SOURCES: An English-language literature search of MEDLINE was conducted. STUDY SELECTION: Human clinical trials were selected for evaluation. DATA SYNTHESIS: Cetirizine, an investigational agent and a potent histamine1 antagonist is a piperazine derivative and carboxylated metabolite of hydroxyzine. As a second-generation, nonsedating antihistamine, cetirizine is associated with fewer adverse effects compared with first-generation antihistamines. It appears to be at least as effective as the other nonsedating antihistamines in the treatment of allergic rhinitis, chronic idiopathic urticaria, and pollen-induced asthma. The recommended adult dosage of this agent is 5 or 10 mg/d. CONCLUSIONS: Clinical studies indicate that cetirizine may be more beneficial in some ways than other available agents. Two of these advantages are a rapid onset of action and a once-daily dosing regimen. Future postmarketing surveillance is warranted to further document these findings. PMID- 8477126 TI - Stroke prophylaxis: hypertension management and antithrombotic therapy. AB - OBJECTIVE: To review trials involving risk factor management and pharmacologic therapy for the prevention of stroke. DATA SOURCES: English-language literature published between 1966 and 1992 was analyzed; pertinent literature is reviewed. STUDY SELECTION: Studies that evaluated the impact of risk factor management on prevention of vascular events were selected. In addition, trials assessing the safety and efficacy of pharmacologic intervention in primary and secondary stroke prevention were evaluated. DATA EXTRACTION: Trials were evaluated for their ability to demonstrate a decrease in stroke occurrence. DATA SYNTHESIS: Various trials were analyzed in several categories. Studies evaluating risk factor management of hypertension and cardiogenic cerebral emboli were reviewed and recommendations made based on a consensus of these trials. The use of antiplatelet agents in stroke prevention was addressed by a review of pertinent trials and meta-analyses. CONCLUSIONS: The control of risk factors and the use of antiplatelet agents significantly reduces the risk of vascular events. Benefit from different therapies may be specific to certain patient populations and recommendations are made for these patients. PMID- 8477127 TI - Vancomycin pharmacokinetics in neonates and infants: a retrospective evaluation. AB - OBJECTIVE: To evaluate the frequency with which current loading and maintenance vancomycin dosages achieve target serum concentrations based on pharmacokinetic parameters obtained after the initial dose. Also, to identify the daily vancomycin dosage necessary to achieve target serum concentrations at steady state and to determine if any relationships exist between vancomycin pharmacokinetic parameters and various patient characteristics. SETTING: Neonatal intensive care unit (NICU) at Georgia Baptist Medical Center. PATIENTS/METHODS: Twenty-three infants with suspected or documented gram-positive infection who received intravenous vancomycin between July 1990 and November 1991 were included in this retrospective analysis. Gestational age range from 23 to 41 weeks and postconceptional age (PCA) at the time of the study ranged from 26 to 46 weeks. Vancomycin therapy was initiated with a loading dose of 15 mg/kg, followed by a maintenance dosage of 20-30 mg/kg/d, which was usually given as 10 mg/kg q8-12h. All vancomycin doses were administered using a syringe pump. Peak and trough serum concentrations were obtained following the first dose. Vancomycin pharmacokinetic parameters were determined using a one-compartment model. Infants receiving indomethacin within two weeks prior to study were analyzed separately (group 2, n = 4). All other infants were included in group 1 (n = 19). RESULTS: For group 1, vancomycin clearance (Cl), volume of distribution (Vd), and half life were (mean +/- 1 SD) 0.072 +/- 0.032 L/kg/h, 0.52 +/- 0.08 L/kg, and 5.6 +/- 1.6 hours, respectively. For both groups, loading doses provided 1-hour postinfusion peak concentrations of 25-35 mg/L in one of every two infants studied, whereas only three percent of initial maintenance doses were projected to provide desired peak and trough concentrations at steady-state. For group 1, the mean daily dosage necessary to provide target peak (25-35 mg/L) and trough (5 10 mg/L) concentrations at steady-state was larger than that initially prescribed (29.6 +/- 13.1 vs. 22.2 +/- 4.7 mg/kg/d). For group 2, the mean daily dosage required to achieve target peak and trough concentrations at steady-state was smaller than that initially prescribed (14.8 +/- 4.3 vs. 20.0 +/- 0.1 mg/kg/d) and was exactly half of that required for group 1. Excellent correlations were observed between PCA and vancomycin Cl (L/h) (r = 0.92; p < 0.0001), body weight and Vd(L) (r = 0.94; p < 0.0001), body weight and vancomycin Cl (L/h) (r = 0.85; p < 0.0001), PCA and Vd (L) (r = 0.89; p < 0.0001), and body surface area and Vd (L) (r = 0.93; p < 0.0001) for group 1. Moderate correlations were also noted between PCA and Cl relative to body weight (L/kg/h), postnatal age and Cl (L/kg/h), and PCA and vancomycin dosage requirements (mg/kg/d). No linear correlation was observed between any patient characteristic and Vd standardized for body weight. CONCLUSIONS: Our data demonstrate the need for a more accurate method of estimating initial vancomycin dosage requirements in this NICU population. Although some of the relationships revealed in this study could be used to determine vancomycin dosage for infants in the range of approximately 30 36 weeks PCA, we hesitate to suggest this approach presently because of the potential limitations of our study design. Further prospective study is needed to confirm these observations. In addition, further study is necessary to describe the time course of the interaction between vancomycin and indomethacin in infants with successful and unsuccessful closure of their patent ductus arteriosus. PMID- 8477128 TI - Prospective surveillance of imipenem/cilastatin use and associated seizures using a hospital information system. AB - OBJECTIVE: To develop computerized methods to monitor and recommend dosage changes for patients treated with excessive dosages of imipenem/cilastatin (I/C) and to determine the incidence of I/C-associated seizures in our patient population. DESIGN: Prospective observational and interventional study of all patients admitted to LDS Hospital and treated with I/C from May 1, 1987, through June 30, 1991. SETTING: LDS Hospital, Salt Lake City, UT, a 520-bed, tertiary care center associated with the University of Utah School of Medicine. PATIENTS: Using a hospital information system we developed computerized algorithms to identify and monitor patients receiving I/C. These algorithms screened the computer-stored medical records of all inpatient admissions for I/C prescription orders. Computer-decision support algorithms estimated the renal function of each I/C-treated patient and provided suggestions when dosages were determined to be excessive. Additional computer-generated alerts identified patients who were receiving anticonvulsants concomitantly with I/C or whose therapy reflected dosage changes in the previous 24 hours. A list of all I/C-treated patients with alerts was reviewed daily by a clinical pharmacist and prescribing physicians were contacted if the computer-generated suggestions were clinically relevant. MAIN OUTCOME MEASURE: The number and characterization of I/C-associated seizures. RESULTS: From May 1, 1987, through June 30, 1991, we prospectively monitored 107,600 patients of whom 1951 were treated with I/C. The following risk factors for I/C-associated seizures were observed in the I/C-treated population: CNS disease (6 percent), seizure disorders (0.6 percent), and abnormal renal function (70 percent). The observational and interventional methods employed in this study resulted in 79 percent of the patients receiving I/C dosages appropriate for their corresponding renal function. During the 50-month study period, we detected four seizures (0.20 percent) in the I/C-treated patients. All 4 patients were receiving I/C dosages that were excessive with respect to their renal function. CONCLUSIONS: Our rate of seizure (0.2 percent) was lower than the 1-2 percent rate reported in the literature despite the fact that more than 70 percent of the patients who received I/C had risk factors for seizure. We believe that appropriate dosing of I/C results in a low rate of associated seizures. Computer assisted monitoring of I/C dosages in relation to renal function resulted in a reduced incidence of seizures. PMID- 8477129 TI - Therapeutic drug monitoring in ambulatory care. AB - There is a growing emphasis on developing ambulatory care services in an attempt to minimize healthcare costs through preventive medicine and outpatient therapeutic management. This creates an environment that can greatly benefit from a pharmacist-managed ambulatory TDM service. The implementation of a pharmacist managed TDM service can improve patient care, contain the cost of healthcare, and enhance the education of pharmacy/medical students and physicians. The opportunity exists for further development of clinical pharmacy services to positively influence patient care in the ambulatory care setting. This development, however, may be hindered by inadequate reimbursement for services and lack of documentation to support the beneficial impact of clinical pharmacy services on patient outcome. Methods of documenting clinical pharmacists' interventions and outcome must be developed in order to obtain reimbursement for these services. PMID- 8477130 TI - Triazolam and nitrazepam use in elderly outpatients. AB - OBJECTIVE: To determine adverse reactions and effects on sleep among three groups of patients: those taking triazolam, those taking nitrazepam, and a control group. DESIGN: Telephone interviews. PATIENTS: Forty-seven patients taking triazolam, 36 taking nitrazepam, and 40 control patients. All study participants were outpatients over 60 years of age. RESULTS: The rate of awakening in the middle of sleep was not significantly different among patients taking triazolam (61.7 percent) and those taking nitrazepam (69.4 percent). Incidence of nocturia, the primary reason for awakening, was not significantly different between triazolam- (36.2 percent) and nitrazepam-taking patients (41.7 percent). The rate of having difficulty falling back to sleep was significantly different among triazolam (62.1 percent) and nitrazepam (8 percent), and triazolam and control (11.1 percent) groups (p < 0.01). No difference was evident, however, between nitrazepam and control groups. CONCLUSIONS: Patients taking nitrazepam have less difficulty returning to sleep compared with those who take triazolam. Thus, for elderly patients who awaken because of nocturia, nitrazepam may be more appropriate therapy. PMID- 8477131 TI - Treatment of idiopathic thrombocytopenic purpura using a dose of immunoglobulin based on lean body mass. PMID- 8477132 TI - Reversible renal insufficiency following ketorolac therapy. PMID- 8477134 TI - Outcome and income. PMID- 8477133 TI - Weight gain induced by long-term propranolol treatment. PMID- 8477135 TI - Gender differences in pain and cardiovascular responses to forearm ischemia. AB - OBJECTIVE: To examine gender-related differences in pain and cardiovascular responses to forearm ischemia. DESIGN: Forearm ischemia was produced by the submaximal effort tourniquet procedure. Participants performed 2 min of dynamic hand exercise at 30% maximum grip strength. Forearm ischemia was maintained until the report of ischemic pain tolerance or until 20 min elapsed. Arterial blood pressure, heart rate, and verbal reports of ischemic pain were assessed at 2 min intervals. SUBJECTS: Thirty four male and 33 female participants of similar age. RESULTS: The times to ischemic pain onset and ischemic pain tolerance were similar for both male and female participants. However, during the ischemic period, females reported ischemic pain to be more intense and of greater unpleasantness than male participants. The relative changes in arterial blood pressure and heart rate during the exercise and occlusion period were equivalent for both male and female participants. In contrast, arterial blood pressure responses during the postexercise ischemic period were gender-dependent. Arm ischemia evoked pressor responses in male participants and either a decrease or no change in arterial pressure in female participants. Changes in arterial pressure during the postexercise ischemic period were significantly and positively correlated with verbal measures of ischemic pain for male subjects but not for female subjects. CONCLUSIONS: The data demonstrated that gender influences both the sensory and the cardiovascular responses to a tonic noxious stressor. PMID- 8477136 TI - Pediatric PCA: the role of concurrent opioid infusions and nurse-controlled analgesia. AB - OBJECTIVES: We designed a clinical study to determine: a) the safety and efficacy of patient-controlled analgesia (PCA) therapy in children and adolescents undergoing major operations, b) if the use of a concurrent opioid infusion improved the efficacy of conventional PCA therapy, and c) if nurse control of the PCA device was a useful alternative in the intensive care unit (ICU) setting. DESIGN: Subjects were randomly assigned to receive morphine sulfate for postoperative pain relief via intermittent PCA boluses on demand or PCA plus a continuous infusion (PCA + CI). Children (n = 12) who were unable to use the PCA device because of inadequate development level or upper extremity weakness were assigned to a nurse-controlled analgesia (NCA) group. SETTING: In the ICU of a university-based pediatric teaching hospital. PATIENTS: Fifty-four children and adolescents underwent elective scoliosis surgery. INTERVENTIONS: The PCA devices were connected to the patient's i.v. catheter immediately after surgery. Morphine sulfate was administered on demand by either the patient or an ICU nurse for pain relief during the first 72 h after the operation. MAIN OUTCOME MEASURES: Pain scores were recorded simultaneously by both the nurse and the patient using standardized visual analog scales. Opioid analgesic usage, side effects, and therapeutic interventions were recorded by the ICU nurse. RESULTS: There were no differences between the PCA and PCA + CI groups with regard to morphine use, pain relief, side effects, or patient satisfaction. Nurses consistently underestimated their patient's level of pain, and children in the NCA groups received less morphine per kilogram than those who self-administered their own analgesic medication. CONCLUSIONS: Both PCA and NCA were safe and efficient methods of analgesic administration in the pediatric ICU setting. However, use of a concurrent opioid infusion with PCA therapy did not provide any clinically significant advantages over intermittent bolus doses of the analgesic medication after scoliosis surgery. For patients unable to use a conventional PCA device, NCA is an acceptable alternative for the management of acute pain in the ICU setting. PMID- 8477137 TI - The prediction of return to the workplace after Multidisciplinary Pain Center treatment. AB - The prediction of return to the workplace after Multidisciplinary Pain Center (MPC) treatment has become a major research area. To delineate the variables that predict this outcome, the authors reviewed 164 multidisciplinary variables studies. Of these, 79 addressed work as an outcome variable. Twenty-six studies attempted to identify patient variables predicting return to the workplace. These latter studies were critically inspected for eight methodological criteria: pain location, follow-up time interval, response percentage and follow-up method, return to work subcategorization, vocational movement, univariate vs. multivariate statistics, multi-colinearity and variance, and statistical treatment of dropouts. In addition, other disability studies besides those in the chronic pain area were reviewed for return to the workplace predictor variables. Of these 26 studies, only a few appeared to satisfy the criteria examined. In addition, many studies were in conflict with one another on whether a variable was predictive. The review of the nonchronic pain/disability prediction literature yielded a large number of potential predictors that related to the work area. It is unclear which variables or set of variables predict return to the workplace after MPC treatment. Chronic pain studies may be neglecting the work area as an important source of return to the workplace predictor variables. PMID- 8477138 TI - Pain-relevant support as a buffer from depression among chronic pain patients low in instrumental activity. AB - OBJECTIVE: This study examined the hypothesis that among chronic pain patients lacking participation in activities, perceived pain-relevant spousal support would act to compensate for a low level of social reinforcement and provide a buffer against depression. DESIGN: Hierarchical regression analyses were conducted to examine the relative and cumulative effects of support and activity, and their interactions, in the prediction of depression severity. SETTING: The study setting was a training and research oriented Veterans Administration Medical Center. PATIENTS: Participants were 105 married, male chronic pain patients evaluated for a comprehensive pain management program. MAIN OUTCOME MEASURE: Depression severity was measured by the Beck Depression Inventory. RESULTS: Three categories of activity, and perceived interference of pain accounted for significant proportions of the variance in depression severity scores beyond that accounted for by age and pain severity. Support was not predictive of depression. Interactions between interference and support, and between two of the specific activities and support added significantly to the prediction of depression. CONCLUSIONS: Results are consistent with a buffering model of social support in which perceived spousal support among chronic pain patients appears to moderate the potentially deleterious effects of a low level of activity. PMID- 8477139 TI - Behavioral management of chronic pain and excess disability: long-term follow-up of an outpatient program. AB - OBJECTIVE: To assess the overall efficiency of an outpatient behavioral rehabilitation program for excess disability and chronic pain and to describe the program staff, treatment components and outcomes in sufficient detail to facilitate comparison with similar programs. DESIGN: Eight-year follow-up study of patients referred and treated. SETTING: Outpatient primary care and multispecialty group medical practice. PATIENTS: 354 of 421 unselected patients referred for the behavioral management of excess disability, who completed the treatment program and participated in follow-up. INTERVENTIONS: 15-20 sessions of physical and occupational therapy, 5-10 sessions of biofeedback, and one or two family sessions all based upon behavioral techniques described by Fordyce and by Roberts. MAIN OUTCOME MEASURES: Questionnaires, including analog scales, administered before treatment and at 1, 6, 12, and 24 months posttreatment. RESULTS: Patients (n = 67) who dropped out did not differ systematically from those who participated (n = 354). The treatment program resulted in a marked and enduring reduction of pain, and a statistically and clinically significant improvement in patients' ability to function at work and in the home. Patients overwhelmingly endorsed the program. CONCLUSIONS: A brief, inexpensive, outpatient behavioral rehabilitation program for chronic pain and excess disability can achieve a clinically significant and lasting reduction of pain and improvement in function at work and at home. PMID- 8477140 TI - The effects of multidisciplinary pain management treatment on locus of control and pain beliefs in chronic non-terminal pain. AB - OBJECTIVE: To determine whether chronic pain patients' beliefs and attributions about pain control are amenable to change in a short-term inpatient multidisciplinary pain management program. DESIGN: Non-randomized consecutive sample with prospective, before-after treatment. SETTING: Pain-management, tertiary care center in a major U.S. city. PATIENTS: All adult patients (n = 50) who were treated in an inpatient multidisciplinary pain management center were contrasted with those of a control group of 46 adult patients who were treated in an outpatient pain center. OUTCOME MEASURES: Pain Locus of Control Scale, the Pain Beliefs and Perceptions Inventory, subjective pain intensity, and medication usage were measured before and after treatment. RESULTS: Statistically significant posttreatment changes were found for the treatment group, but not the control group. Patients who completed the inpatient pain management program reported significant decreases in subjective pain intensity despite discontinuation of narcotic analgesics. Patients in the treatment group showed an increased sense of personal control over their pain and substantial decreases in attributions of pain control to powerful others and chance. Patients in the treatment group also showed a significant reduction in their endorsement of the belief that their pain was a mysterious phenomenon. CONCLUSIONS: Chronic non terminal pain patients' beliefs about pain and attributions of pain control are amenable to change in a short-term inpatient multidisciplinary pain management program. These results suggest that an intensive multidisciplinary program involving psychotherapy might be more effective in treating chronic pain patients similar to those in this study than outpatient treatment without psychotherapy. PMID- 8477141 TI - Physical fitness in the management and prevention of chronic pain. PMID- 8477143 TI - Use of standardized notes on laser-printed labels for acute pain management rounds. PMID- 8477142 TI - Topical capsaicin and burning pain. PMID- 8477144 TI - In response to RSD article by Drs. Gibbons and Wilson. PMID- 8477145 TI - Postmenopausal breast cancer. Drug therapy in the 1990s. AB - In summarising current drug treatment strategies for postmenopausal women with breast cancer, it is essential to emphasise that we are dealing with a group of diseases that are treatable, and that appropriate treatment decisions will give longer disease-free intervals for patients with early breast cancer, and better control with better survival for patients with advanced (i.e. locally advanced and/or metastatic) disease. Women greater than 65 years of age have a predictably better response to hormone treatment versus women less than 65 years of age. Hormone treatment may, therefore, be considered as primary treatment or as adjuvant treatment after limited surgery. Hormone treatment is also the treatment of first choice for elderly patients with advanced disease. For middle-aged women (45 to 65 years of age), various patient factors are important in predicting the value of treatment. Estrogen receptor (ER) status is prognostic of survival irrespective of treatment. Patients with ER-positive disease have a better prognosis than those with ER-negative disease, both in the adjuvant setting and in the face of metastatic disease. This is because ER-positive tumours tend to grow slower. The availability of the serotonin type 3 (5-hydroxytryptamine;5-HT3) antagonists, which effectively control nausea and vomiting in most patients, make chemotherapy combinations more acceptable, and combination chemotherapy can more readily be considered as first treatment option both as adjuvant treatment and for treatment of advanced disease. For patients with organ metastases there is no doubt that combined chemotherapy treatment is indicated. PMID- 8477146 TI - Mental health in nursing homes. Perspectives on the use of medication. AB - Most elderly persons in nursing homes and residential care have mental disorders; up to 75% have dementia. Depression and behavioural problems are common. There are big differences between institutions in the proportion of residents prescribed psychotropic medication. A review of the literature suggests that antipsychotics and benzodiazepines are modestly effective in diminishing agitation in some dementing patients. Antidepressants may be underutilized, but clear guidelines about which depressed individuals should receive them are lacking. Attention should be given to ways of improving the environment within these homes, in order to relieve depression and anxiety, and to increase life satisfaction and self-esteem, before commencing psychotropic medication to deal with mental disturbances. Shortage of trained staff and inappropriate design of nursing homes are factors associated with behavioural disturbance in some cases. Special dementia care units are a desirable option for a minority of residents. Involvement of pharmacists and medical directors in monitoring effects, adverse side effects, possible interactions and appropriateness of medications in nursing homes is recommended. PMID- 8477147 TI - Drug-induced depression in the aged. What can be done? AB - Over 10% of medically ill elderly persons have concurrent major depression, and medical illness is the most influential stressor contributing to depression in old age. The contribution of prescribed medications to depression in the medically ill is poorly understood. Most information on drug-induced depression is derived from case reports; 43 classes of medications have been implicated, including reserpine, beta-blockers, levodopa, corticosteroids, and antipsychotics. However, large rigorously performed studies of some drugs, particularly antihypertensives, suggest that drug-induced depression is uncommon and idiosyncratic. There is no evidence that age is an independent risk factor for drug-induced depression. However, elderly persons are the largest consumers of prescribed drugs, and the burden of drug-induced depression is carried by the old. Because of the frequency of atypical presentations of mental disorders in the elderly, drug-induced depression is often misdiagnosed. Nevertheless, basic principles of geriatric medicine offer useful guidance to clinicians in evaluating the complex interrelationships between prescribed medications and depression. We recommend an approach that includes regular inquiry into the common symptoms of mood disorders, vigilance in assessing the contribution of drugs in their development, but scepticism in assessing a depressive episode as caused only by medication. PMID- 8477148 TI - Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer's type. AB - A multicentre, randomised, controlled study compared the efficacy of l-alpha glyceryl-phosphorylcholine (alpha GPC) and ST200 (acetyl-l-carnitine) among 126 patients with probable senile dementia of Alzheimer's type (SDAT) of mild to moderate degree. Efficacy was evaluated by means of behavioural scales and psychometric tests. The results showed significant improvements in most neuropsychological parameters in the alpha GPC recipients. Improvements also occurred in the ST200 recipients but to a lesser extent. Tolerability was good in both groups. These positive findings require replication in larger, double-blind, longitudinal studies coupling clinical and biological determinations. PMID- 8477151 TI - On the nomenclature and classification of anti-asthma drugs. PMID- 8477149 TI - Nicardipine. A review of its pharmacology and therapeutic efficacy in older patients. AB - Nicardipine is a second generation dihydropyridine calcium antagonist which selectively inhibits vascular smooth muscle contraction. In elderly patients, the drug has demonstrated clinical efficacy in the management of hypertension, angina pectoris and ischaemia-related cerebrovascular disease. In particular, nicardipine effectively controls blood pressure in elderly hypertensive patients with or without coexistent disease. In noncomparative trials, a regimen containing nicardipine has been associated with an improvement of symptoms in hypertensive patients with concurrent coronary artery, cerebrovascular or peripheral vascular disease, while in essentially 'healthy' elderly hypertensive patients, nicardipine monotherapy has resulted in improved indices of mobility and cognitive function. As yet, however, there is no evidence that nicardipine (and/or other calcium channel antagonists) decreases cardiovascular morbidity and mortality in elderly patients, as has been demonstrated for more established antihypertensive therapies, namely diuretics and/or beta-blockers. The pharmacokinetic properties of nicardipine in elderly hypertensive patients appear to be similar to those in younger patients. The main adverse events associated with nicardipine in the elderly are related to the vasodilator properties of the drug and include pedal oedema, headache and flushing. However, the drug does not exacerbate spontaneous postural hypotension in the elderly, nor does it adversely affect the coronary artery disease risk profile, even in patients with type II diabetes mellitus. In summary, widespread clinical experience in the elderly indicates that nicardipine monotherapy or a regimen containing nicardipine is useful for the treatment of hypertension, particularly in patients with coexistent coronary artery, cerebrovascular or peripheral vascular disease. Nicardipine monotherapy has also demonstrated efficacy in angina pectoris and shown promise in the management of ischaemia-related cerebrovascular diseases, notably subarachnoid haemorrhage. PMID- 8477150 TI - Can thiazide diuretics be recommended routinely to reduce hip fracture risk? PMID- 8477152 TI - Comparison of a phospholipid-based protein-free surfactant and a natural bovine surfactant (SURVANTA) during pressure and volume-controlled ventilation in an improved rabbit fetus model. AB - During pressure- or volume-controlled ventilation different surfactant preparations were compared in an improved rabbit fetus model. Based on a self designed software program, this model enables on-line registration of lung mechanics and heart rate in up to ten fetuses. Using a commercially available bovine lung surfactant (SURVANTA) as standard, we compared animals treated with a protein-free surfactant preparation containing only phospholipids, PL (dipalmitoylphosphatidylcholine:palmitoyloleoylphosphatidylglycerol++ +, DPPC:POPG 70:30) plus palmitic acid (PA) with an untreated ventilated control group. During pressure-controlled ventilation the insufflation pressure (IP) was decreased and increased stepwise with and without positive end-expiratory pressure (PEEP). SURVANTA was significantly more potent than PL plus PA and both differed significantly from the untreated controls. With additional PEEP the differences between SURVANTA and PL+PA disappeared but the differences to the controls were still present. We found that, with additional PEEP, active natural surfactants lead to ECG-irregularities, which indicates that PEEP influences pulmonary and cardiovascular function and compromises the benefits of surfactant therapy. Also during volume-controlled ventilation SURVANTA was superior to PL+PA and the untreated controls. In order to raise the level of activity of pure PL mixtures to that of natural bovine surfactants, we suggest that a surface active protein (probably SP-C) must be added to such mixtures. PMID- 8477153 TI - Inhibition of leukotriene synthesis: new therapy in asthma? PMID- 8477154 TI - Effect of cromakalim on KCl-, noradrenaline- and angiotensin II-induced contractions in the rat pulmonary artery. AB - The effect of cromakalim on vascular reactivity was studied in rat isolated pulmonary arterial strips. Cromakalim (0.1-1 microM) inhibited contractions induced by low (20-30 mM) KCl concentrations in a concentration-dependent manner. It had no effect on those elicited by 60-100 mM KCl. However, a higher concentration of cromakalim (10 microM) slightly decreased (-5 to -10%) KCl efficacy. Contractions induced by noradrenaline (NA, 0.01-1 microM) and angiotensin II (AII, 0.5-50 nM) were reduced by cromakalim (0.1-10 microM). The maximal response to NA and AII was decreased by 54 +/- 6.4% and 70 +/- 5.8% (n = 5), respectively, in the presence of 10 microM cromakalim. The inhibitory effect of cromakalim was not dependent on the presence of vascular endothelium. After blockade of calcium influx by verapamil (10 microM), cromakalim had no further effect on NA- and AII-induced contractions. Cromakalim (0.1-1 microM) had no effect on the amplitude of the transient contraction evoked by NA and AII in Ca(2+)-free solution. The inhibitory effect of cromakalim (1 microM) was reversed by glibenclamide (1-10 microM) and phentolamine (5-100 microM) which, however, did not alter the relaxant effect of verapamil (1 microM), papaverine (1 microM) or theophylline (1 mM). Contractions induced by NA and AII in the presence of tetraethylammonium (TEA, 10 mM) were also depressed by cromakalim. These results show that cromakalim is a potent anticonstrictor agent in the pulmonary circulation. As in other smooth muscles, its mechanism of action involves an interaction with potassium channels at the vascular smooth muscle cell membrane level. PMID- 8477155 TI - Relaxant effects of the potassium channel activators BRL 38227 and pinacidil on guinea-pig and human airway smooth muscle, and blockade of their effects by glibenclamide and BRL 31660. AB - The airways relaxant effects and mechanism of action of the potassium channel activators BRL 38227 and pinacidil have been compared in guinea-pig and human airways. BRL 38227 was a potent relaxant in guinea-pig isolated trachealis (IC50 = 4.9 x 10(-7) M against spontaneous tone) and human isolated bronchi (IC50 = 4.75 x 10(-7) M against histamine-induced tone) and was eight- and six-fold more potent respectively than pinacidil. The relaxant effects of both compounds were shown to be markedly attenuated by glibenclamide (10(-5) M) and BRL 31660 (10(-5) M), with the nature of the blockade being species/tissue dependent. Glibenclamide (20 mg/kg iv) also inhibited the protective effects of BRL 38227 (50 micrograms/kg iv) and pinacidil (500 micrograms/kg iv) on histamine-induced changes in airways resistance and dynamic compliance in the anaesthetized guinea pig, although the effects were short-lived. That both BRL 38227 and pinacidil owed their relaxant effects to potassium channel activation was supported by their ability to stimulate 42/43K efflux from guinea-pig trachealis preloaded with the radiotracer at concentrations of 10(-7) - 10(-5) M and 10(-5) M respectively. Pretreatment with either glibenclamide (10(-5) M) or BRL 31660 (10( 5) M) ablated the response to both compounds. These studies show that two mechanistically distinct potassium channel blockers, glibenclamide and BRL 31660, do not substantially differentiate between the actions of BRL 38227 and pinacidil, although differences do occur, particularly at high concentrations in vitro. PMID- 8477156 TI - Leukotrienes and histamine mediate IgE-dependent contractions of human bronchi: pharmacological evidence obtained with tissues from asthmatic and non-asthmatic subjects. AB - Isolated human bronchi were challenged with anti-human IgE or specific allergen. The mediators of allergic constriction were characterized by pharmacological interventions. Experiments were performed on more than 180 preparations obtained from 48 non-asthmatic subjects and on 44 bronchial preparations from six asthmatic subjects. Addition of antihistamines (mepyramine and metiamide) to the organ bath abolished the response to exogenous histamine, but failed to alter the dose-response relationship of the reaction to cumulative challenge with rising titres of anti-IgE. On the other hand, pretreatment with drugs which blocked the action (receptor antagonists FPL55712, L-648,051 and ICI 198,615) or formation (biosynthesis inhibitors: U-60,257 and MK886) of leukotrienes consistently resulted in clear-cut inhibition of the allergic constriction in bronchi from both asthmatic and non-asthmatic subjects. In the presence of the most effective inhibitors (ICI 198,615 and MK886), the response to anti-IgE was depressed by more than 60%. In contrast, the cyclooxygenase inhibitor indomethacin and the antagonist of platelet activating factor (PAF) WEB 2086, failed to alter the response, indicating that prostanoids and PAF do not mediate IgE-dependent constriction of human bronchi. After the leukotriene antagonist ICI 198,615 had rendered the bronchi insensitive to exogenous leukotrienes, the residual component of the contractile response to anti-IgE was completely abolished by addition of antihistamines. Similar abolition of the Schultz-Dale reaction in bronchi of two allergic asthmatic patients was noted when antihistamines were administered together with ICI 198,615 or MK886. In conclusion, the leukotrienes appear to be the major and singularly most important mediators of the contraction, whereas histamine accounts for its minor residual component. PMID- 8477157 TI - Lower body temperatures in infants delivered by caesarean section than in vaginally delivered infants. AB - Clinical experience suggests that infants delivered by caesarean section have difficulties maintaining normal body temperature during the first hours after birth. To test this hypothesis, body and skin temperatures were measured and compared in healthy full-term caesarean section and vaginally delivered newborn infants. The babies were studied during the first 90 min after birth. Axillary and skin temperatures were significantly higher in the vaginally delivered group than in infants delivered by caesarean section. Infants born by non-elective caesarean section were slightly warmer during the first 90 min after birth compared to infants born by elective caesarean section. There were no significant differences in temperatures between infants cared for in a cot as compared to those cared for in an incubator. An incubator creates a physical barrier between babies and parents and incubator care might cause parental anxiety. Thus the routine of putting healthy, full-term caesarean section infants in incubators can be abandoned from a thermoregulatory point of view. PMID- 8477158 TI - Antigen and antibody assays in the aetiological diagnosis of respiratory infection in children. AB - The diagnostic efficacy of two methods--demonstration of seroconversion in paired sera and detection of antigen in clinical specimens--was evaluated in 183 children with respiratory syncytial, parainfluenza or adenoviral, or pneumococcal respiratory tract infection. Viral infection was diagnosed in 46 (37%) of the 125 cases by antigen assay alone, in 36 (29%) by antibody assay alone and in 43 (34%) by both methods. In respiratory syncytial viral infections, antigen assays were more often positive than antibody assays; 80% of the cases were antigen positive and 63% solely antigen positive. In parainfluenza and adenoviral infections, antigen assays were not as useful; a positive result was seen in 59% and 44% of cases, respectively. Pneumococcal infection was diagnosed in 25 (30%) of the 84 cases by antigen assay alone, in 54 (64%) by antibody assay alone and in only 5 (6%) by both methods. Thus nearly all pneumococcal infections were diagnosed by only one method. The efficacy of antigen and antibody assay was clearly dependent on the age of the patients. In infants less than six months of age, nearly all (27 (90%)) of the 30 infections were diagnosed by antigen detection; 25 solely by antigen detection. In older patients, antigen and antibody assays supplemented each other. We conclude that antigen detection should be used as the primary method for the diagnosis of viral or pneumococcal respiratory tract infection. In infants, antigen detection is the only reliable method of microbial diagnosis. In addition, antigen detection is the method of rapid microbial diagnosis. In pneumococcal infections, the sensitivities of antigen detection methods are not sufficient; this is an important area for further research. PMID- 8477159 TI - Carnitine metabolites in infants with cystic fibrosis: a prospective study. AB - Acylcarnitine is low in cord blood in patients with cystic fibrosis, suggesting that fatty acid metabolism is disturbed in utero. Carnitine metabolites (total, free, short- and long-chain acylcarnitine) were measured prospectively in 23 newly diagnosed infants with cystic fibrosis treated with a carnitine-containing, predigested formula for 6-12 months. Total (p < 0.002), free (p < 0.004), and long-chain (p < 0.001) plasma concentrations of carnitines were significantly less than controls (n = 48) at diagnosis. Total and free concentrations were corrected with nutritional management, whereas short- and long-chain acylcarnitines remained unchanged. By three years of age all plasma concentrations of carnitine metabolites were significantly less than controls despite a carnitine-containing diet. Urinary carnitine metabolites were increased at diagnosis and follow-up. The physiological significance of these observations in cystic fibrosis is unknown, but could be compatible with disturbed regulatory control with resultant increased utilization. PMID- 8477160 TI - Magnetic resonance and the diagnosis of short stature of hypothalamic-hypophyseal origin. AB - Magnetic resonance imaging was performed in 23 patients with short stature (7 had multiple pituitary hormone defect, 11 had isolated growth hormone deficiency and 5 had normal variant short stature) to investigate if there is a relation between magnetic resonance findings and results of endocrine tests. Magnetic resonance imaging of patients with multiple pituitary hormone deficiency or with serious isolated growth hormone deficiency (growth hormone < 3 micrograms/l) revealed an interrupted pituitary stalk and ectopic neurohypophysis or a mass. In patients with less serious isolated growth hormone deficiency (growth hormone > 3 micrograms/l) or with normal variant short stature, the technique revealed a normal or hypoplastic hypophysis. Magnetic resonance appears to be a useful second-level diagnostic tool in defining the type of alteration in growth defects of endocrine origin. PMID- 8477161 TI - Coronary risk factors in children of parents with premature coronary artery disease. AB - In order to assess the value of family history of premature coronary artery disease as a criterion for coronary risk factor screening, a group of 53 children with such a family history was selected. We determined various coronary risk factors in these children in comparison to 33 controls. Statistically significant differences were observed in apoprotein concentrations but not in concentrations of lipids, lipoproteins or glucose, or in blood pressure or body mass index. The ratio between apoprotein B and apoprotein AI was the best discriminator between the two groups. The predictive value of family history is more reliable for detecting abnormal apoprotein ratio than for detection of hypercholesterolemia. We conclude that if abnormal apoprotein levels during childhood are found to be a valued predictor of premature coronary artery disease, then family history of premature coronary artery disease can be used to select children for determination and assessment of their coronary risk. PMID- 8477162 TI - Energy and nutrient intakes in congenital heart disease. AB - Children with congenital heart disease may have significant growth retardation, which in part may be caused by insufficient dietary intake. Data on energy and nutrient intake were collected using a 14-day dietary record by weighing, in 22 children with congenital heart disease (mean age 39 months, range 12-126 months), prior to corrective operation. When viewed in relation to actual weight, energy intake averaged 88% (SD 17%) of that recommended by the FAO/WHO/UNU. Energy intakes and weight SD scores were significantly correlated (r = 0.55, p < 0.01). Protein intake was generally high, and even sufficient to allow catch-up growth. The majority of the children did not meet the recommendations for iron, zinc, calcium, or vitamins D, E, C, B1 or B6. Parents should be advised to give their children vitamin/mineral supplements, and to supply extra energy to children with failure to thrive. PMID- 8477163 TI - Randomized trial of umbilical arterial catheter position: clinical outcome. AB - In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the "high" group and nine in the "low" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis. PMID- 8477164 TI - Cessation of smoking during pregnancy improves foetal growth and reduces infant morbidity in the neonatal period. A population-based prospective study. AB - All pregnant women in Uppsala county in 1987 were questioned on three different occasions about smoking habits, socio-demographic factors and obstetric history. After delivery, information was collected regarding their children. Twenty percent of the mothers continued to smoke during pregnancy, while 8% stopped smoking. The mean birth weight of infants of smokers was 3378 g and of non smokers 3589 g. The difference was significant (p < 0.001) and persisted after statistical adjustment for maternal age, parity and educational level. Perinatal morbidity (admission to the Department of Neonatology) was higher in the smoking group (11.4% versus 8.8%, p < 0.05). The proportion of infants with a birth weight less than 2500 g and that of small-for-gestational-age infants were 60% and 100% greater, respectively, in the smoking group. The mean birth weight and perinatal morbidity rate in infants of mothers who stopped smoking were almost identical to those in infants of non-smokers. Cessation of smoking improves foetal growth and perinatal health. PMID- 8477165 TI - Surfactant inhibition in experimental meconium aspiration. AB - Human meconium components were separated into a water-methanol soluble phase containing mainly proteins and bilirubin and a chloroform soluble phase containing free fatty acids, triglycerides and cholesterol. Various amounts of original meconium, the water-methanol soluble fraction or the chloroform soluble fraction were added to standard suspensions of porcine surfactant (Curosurf). In a pulsating-bubble or Wilhelmy-balance system, meconium and its subfractions inhibited surfactant activity, but the chloroform soluble fraction had the highest specific inhibitory activity. Original meconium in saline (130 or 65 mg/ml) was instilled into the airways of ventilated near-term newborn rabbits (dose 6 ml/kg). Lung-thorax compliance was reduced by 38% in animals aspirating the higher dose and by 27% in the low-dose group. Histological sections showed intra-alveolar accumulation of fine meconium particles in experimental animals, but no plugging of larger airways. We conclude that respiratory failure from meconium aspiration may be mediated, in part, by inactivation of surfactant. PMID- 8477166 TI - One-sided high-frequency oscillating ventilation in the treatment of neonatal unilateral pulmonary emphysema. AB - We describe a preterm infant (31 weeks' gestation) with unilateral pulmonary emphysema. Bronchoscopy showed no bronchial obstruction. After 20 days of right sided high-frequency oscillating ventilation, the emphysema in the left lung had completely resolved and the patient could be extubated. PMID- 8477167 TI - Early treatment with nasal continuous positive airway pressure in very low-birth weight infants. AB - During 1988 and 1989, a regional cohort of 81 infants with birth weights less than 1501 g were treated with oxygen only (n = 11), early continuous positive airway pressure (CPAP) (n = 68) or mechanical ventilation from birth (n = 2). We used an easily applicable lightweight CPAP system with nasal prongs and a gas jet supplemented with ventilator treatment if necessary, but with conservative criteria for ventilator treatment with tolerance of high PCO2. A total of 65 infants (80%) survived to discharge, 61 of whom were supported solely with CPAP or oxygen. Nineteen infants (26%) developed periventricular-intraventricular haemorrhage, but only 4 survivors (6%) developed prognostically significant bleedings grade 2-4. No survivors had bronchopulmonary dysplasia. Follow-up at 12 39 months of age revealed definite disabilities in 6 (10%) and suspected disabilities in 2 of 62 long-term survivors. The results suggest that treatment by early CPAP with nasal prongs with tolerance of high PCO2 may be effective and lenient in most infants more than 25 weeks' gestation. PMID- 8477168 TI - Chronic lung disease of preterm infants in Finland is not associated with Ureaplasma urealyticum colonization. AB - The occurrence of Ureaplasma urealyticum and Mycoplasma hominis in the airways and the association of these microorganisms with chronic lung disease was studied in preterm infants with a gestational age less than 30 weeks. Tracheal aspirates from 49 preterm infants were cultured; 14 (29%) infants were positive for U. urealyticum, and 1 (2%) was positive for M. hominis. Of the 16 patients who developed lung disease, 6 (38%) were positive for U. urealyticum, while the expected number of Ureaplasma-positive patients in this group, based on the overall incidence of Ureaplasma, was 4.6. On the other hand, 8 patients were positive for U. urealyticum but did not develop chronic lung disease, nor did samples taken from 10 patients with chronic lung disease show any Ureaplasma growth. From these data we conclude that colonization of the airways with U. urealyticum has no significant role in the development of chronic lung disease in preterm infants in the Finnish (Caucasian) population. PMID- 8477169 TI - Urinary malondialdehyde concentration in preterm neonates: is there a relationship to disease entities of neonatal intensive care? AB - In a retrospective study, urinary malondialdehyde concentration in 45 preterm neonates (25-35 weeks' gestation) during their first month of life was measured by HPLC. Urine was collected on different days of life as a 3-h sample. The frequency of urine collection and measurement varied between one (n = 22) and seven times (n = 8) per child. The study group was divided into three categories according to birth weight: low-birth-weight infants (LBW) (n = 16), very low birth-weight infants (VLBW) (n = 17) and extremely low-birth-weight infants (ELBW) (n = 12). Urinary malondialdehyde concentration was highest in the ELBW group: 1.15 (0.66, 2.12) mumol/l (median and quartiles) versus 0.58 (0.34, 1.18) mumol/l in the VLBW and 0.60 (0.40, 1.06) mumol/l in the LBW groups (ELBW versus VLBW, p < 0.005; ELBW versus LBW, p < 0.02). In oxygen-treated neonates, significantly higher malondialdehyde values were found compared to those without supplementary oxygen (0.89 (0.48, 1.74) versus 0.58 (0.32, 0.89) mumol/l; p < 0.005). Likewise, a higher malondialdehyde concentration was found in infants requiring mechanical ventilation (intermittent mandatory IMV or high frequency ventilation) compared to those breathing spontaneously (intermittent mandatory ventilation: 0.80 (0.42, 1.66); p > 0.05 and high frequency ventilation: 1.20 (0.83, 2.13); p < 0.001 versus 0.57 (0.33, 0.88) mumol/l). Malondialdehyde concentrations correlated significantly with FiO2 values of the individual patients (r = 0.22; p < 0.02). Comparing urinary malondialdehyde concentrations in infants with and without bronchopulmonary dysplasia, a significantly higher malondialdehyde concentration was found in the former group (0.96 (0.51, 2.07) versus 0.60 (0.32, 0.98) mumol/l; p < 0.005)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477170 TI - Children of alcoholic parents. PMID- 8477171 TI - Nasal continuous positive airway pressure: experiences with a new technical approach. PMID- 8477172 TI - No evidence for seasonality of congenital hypothyroidism in The Netherlands. PMID- 8477173 TI - Growth hormone hypersecretion in Sotos' syndrome? PMID- 8477174 TI - A case of Burkitt's lymphoma presenting with digital ischaemia. AB - Paraneoplastic syndromes are rare in paediatric oncology. This report describes a four-year-old Cantonese child whose sole presenting symptom was acrocyanosis who was found to have Burkitt's lymphoma in association with the presence of positive antinuclear antibodies, antineutrophil cytoplasmic antibodies, antiendothelial antibodies and elevated serum immunoglobulin G concentrations. Digital ischaemia has not been described as a presenting symptom of Burkitt's lymphoma, although this association has been reported in 25 patients with other malignancies. PMID- 8477175 TI - Cardiovascular responses to various autonomic tests in males and females. AB - The results of cardiovascular autonomic reflex tests on 224 healthy, randomly selected subjects were analysed to study possible sex differences in the autonomic responses. The heart rate response to the Valsalva manoeuvre (Valsalva ratio) was greater in females over 50 years than in males of the same age (1.58 +/- 0.34 vs. 1.44 +/- 0.30, p < 0.05). The heart rate response to deep breathing (E/I ratio) was higher in females under 50 years than in males under 50 years (1.37 +/- 0.17 vs. 1.34 +/- 0.18, p < 0.001). The diastolic blood pressure response to isometric handgrip was higher in males under 50 years than in females of the same age (p < 0.05). Although there were sex differences in the magnitude of the responses, the effect of age was similar in males and females and accelerated attenuation of the autonomic responses could not be demonstrated with increasing age. It can be concluded that significant sex differences exist in cardiovascular autonomic responses. The implication of such differences need consideration. PMID- 8477177 TI - Clinical autonomic research--looking back, and also ahead to 1993. PMID- 8477176 TI - Vascular and electromyographic responses evoked in forearm muscle by isometric contraction of the contralateral forearm. AB - There is controversy over whether isometric contraction of the forearm evokes vasoconstriction or vasodilatation in the muscles of the contralateral forearm. In the present study we have investigated in normal man, the effects of isometric contraction of one arm at 75, 50 and 25% maximum voluntary contraction (MVC) on arterial pressure, heart rate, blood flow and vascular resistance of the contralateral forearm and on electromyographic (EMG) activity recorded from that same arm with sensitive, surface electrodes. When EMG activity was not being recorded from the 'resting' arm, isometric contraction of the contralateral arm for 2 min evoked increases in arterial pressure and heart rate whose magnitudes were graded with % MVC and an increase in forearm blood flow and a decrease in forearm vascular resistance at 75, 50 and 25% MVC, indicating vasodilatation. Further experiments in which EMG activity was recorded from the 'resting' arm demonstrated that the decrease in forearm vascular resistance evoked by 75% MVC was associated with a substantial increase in EMG activity of the extensor and flexor muscles of that arm. By contrast, when forearm contraction was performed at 75% MVC whilst subjects viewed the EMG activity in the 'resting' arm on an oscilloscope and kept EMG activity minimal, vascular resistance increased in that arm, indicating vasoconstriction. Further, when subjects performed contraction at 25% MVC whilst showing minimal EMG activity in the contralateral arm, vascular resistance in that same arm increased (from 78 +/- 16 to 124 +/- 29 mmHg/ml/min/100 ml tissue). These results are discussed in relation to those of previous studies. We propose, that in normal man, isometric contraction of the forearm evokes primary vasoconstriction in the muscles of the contralateral forearm, but that this response may be overcome by muscle vasodilatation occurring secondary to unintended muscle contraction or as part of the alerting response to acute stress. PMID- 8477178 TI - Bronchodilator effects of oxitropium bromide, fenoterol, and their combination in normal subjects. AB - Oxitropium bromide is a quaternary anticholinergic compound based on the scopolamine molecule instead of atropine. The purpose of this study was to compare the bronchodilator effects of oxitropium, a beta 2-agonist fenoterol, and their combination, on basal bronchomotor tone in normal subjects. Partial flow volume curve (PEF25), was measured as an index representing bronchomotor tone. The cumulative dose-response curve of oxitropium bromide inhaled from a metered dose inhaler was determined in eleven normal subjects. Measurement of PEF25 was repeated every 1 h for 8 h after inhalation of oxitropium (200 micrograms), fenoterol (200 micrograms), their combination or placebo in six normal subjects in a randomized, single-blinded, placebo-controlled, cross-over manner. As the percentage increase in PEF25 by 200 micrograms of oxitropium (45 +/- 6%) was equivalent to nearly 80% of that by dose of 1,600 micrograms (58 +/- 8%), the dose of 200 micrograms is thought to be appropriate. The group mean percentage increase in the PEF25-time course curve was significantly greater after treatment with the combination than with placebo (p < 0.001) and fenoterol (p < 0.001) but not with oxitropium bromide, while the increase in PEF25 following the combination was significantly greater than that following oxitropium bromide after 2 and 3 h. These findings indicate that in normal subjects oxitropium has a powerful bronchodilator effect and that the addition of oxitropium to fenoterol caused greater bronchodilation in normal subjects. PMID- 8477179 TI - Double-blind placebo controlled randomized trial of indomethacin on urodynamic values measured by radionuclide imaging. AB - The effect of the prostaglandin synthetase inhibitor, indomethacin on urodynamic values measured by radionuclide imaging was studied in 17 men in a double-blind placebo controlled randomized trial. Measurements were made of voiding time, time for 50% emptying, average flow rate, ejection fraction, post-void residual urine volume, voided volume, and total bladder volume. Statistical analyses indicated no placebo-indomethacin differences between the two groups. Although prostaglandins are thought to contribute to the act of micturition by maintenance of bladder tone and contractility, our studies indicate that a standard dose of the prostaglandin inhibitor, indomethacin, did not affect the voiding component of bladder function. Patients need not discontinue prostaglandin inhibitors and other non-steroidal anti-inflammatory drugs with such effects prior to urodynamic testing. PMID- 8477180 TI - Comparison of the bronchodilator activities of oxitropium bromide, fenoterol, and their combination in patients with chronic obstructive pulmonary disease and bronchial asthma. AB - The effects of an antimuscarinic agent, oxitropium bromide (200 micrograms), a beta-2 adrenoceptor agonist, fenoterol (200 micrograms), and their combination, were compared in ten patients with chronic obstructive pulmonary disease and ten patients with bronchial asthma, in a placebo-controlled, single blind crossover trial. In patients with chronic obstructive pulmonary disease, oxitropium and fenoterol produced a significant and similar degree of bronchodilatation. The duration of the bronchodilator effect was 3 h after oxitropium and 4 h after fenoterol, respectively. The combination of oxitropium and fenoterol produced a significantly greater degree of bronchodilatation than either drug alone. The duration of bronchodilatation in combination was 7 h and was considerably longer than that of each drug alone. In patients with bronchial asthma, oxitropium and fenoterol also caused bronchodilatation. Their combination produced a significantly greater degree of bronchodilatation than when either drug was used. The duration of the bronchodilator effects were 5 h after oxitropium, 4 h after fenoterol and 5 h after the combination. We conclude that the combination of oxitropium and fenoterol causes greater bronchodilatation in patients with chronic obstructive pulmonary disease and bronchial asthma than when compared to each drug alone. In the former, the duration of bronchodilatation is additionally prolonged. These combination effects may be of value in the clinical management of these common respiratory disorders. PMID- 8477181 TI - The influence of aspirin on plasma and platelet catecholamine levels, and platelet function in normal man. AB - The aim of the study was to determine whether aspirin influences sympathoadrenal output in normal human subjects. Plasma and platelet adrenaline and noradrenaline levels were measured before and after chronic administration of oral aspirin (300 mg per day for 7 days). Catecholamine concentrations measured immediately following aspirin did not differ from control (pre-treatment) values. Platelet noradrenaline and plasma adrenaline levels were, however, significantly increased 2 weeks after cessation of treatment. Platelet TxB2 generation was significantly reduced following aspirin treatment indicating that platelet cyclooxygenase had been inhibited. Catecholamine concentrations did not correlate with TxB2 generation. In vitro platelet aggregation induced by ADP, adrenaline and collagen was reduced after aspirin providing additional confirmation of cyclooxygenase inhibition. However, the in vivo markers of platelet function, beta-TG and PF4 were unaffected. These data do not provide convincing evidence for an action of aspirin on sympathoadrenal outflow, either directly or via a prostaglandin (thromboxane) mediated effect, although this does not exclude a later, delayed effect. There was no evidence for interactions between thromboxane, catecholamine levels in plasma and platelets, and platelet function. PMID- 8477182 TI - Physical manoeuvres that reduce postural hypotension in autonomic failure. AB - A young female with autonomic failure is described. She successfully reduced the symptoms of orthostatic hypotension by application of physical manoeuvres like leg-crossing, bending forward and placing a foot on a chair. The beneficial effects of these manoeuvres can be explained by a small (10-15 mmHg) increase in mean arterial pressure to a level just sufficient to maintain adequate cerebral blood flow. The underlying common mechanism appears to be an increase of thoracic blood volume by translocation of blood from the vascular beds below the diaphragm to the chest. Instruction in these physical manoeuvres should be part of the management programme to reduce the disabilities arising from postural hypotension in patients with autonomic failure. PMID- 8477183 TI - Non-invasive continuous cardiovascular monitoring in the vasodepressor form of carotid sinus hypersensitivity--confirmation of its value. PMID- 8477184 TI - 1H and 15N resonance assignments and solution secondary structure of oxidized Desulfovibrio vulgaris flavodoxin determined by heteronuclear three-dimensional NMR spectroscopy. AB - Sequence-specific 1H and 15N resonance assignments have been made for all 145 non prolyl residues and for the flavin cofactor in oxidized Desulfovibrio vulgaris flavodoxin. Assignments were obtained by recording and analyzing 1H-15N heteronuclear three-dimensional NMR experiments on uniformly 15N-enriched protein, pH 6.5, at 300 K. Many of the side-chain resonances have also been assigned. Observed medium-and long-range NOEs, in combination with 3JNH alpha coupling constants and 1HN exchange data, indicate that the secondary structure consists of a five-stranded parallel beta-sheet and four alpha-helices, with a topology identical to that determined previously by X-ray crystallographic methods. One helix, which is distorted in the X-ray structure, is non-regular in solution as well. Several protein-flavin NOEs, which serve to dock the flavin ligand to its binding site, have also been identified. Based on fast-exchange into 2H2O, the 1HN3 proton of the isoalloxazine ring is solvent accessible and not strongly hydrogen-bonded in the flavin binding site, in contrast to what has been observed in several other flavodoxins. The resonance assignments presented here can form the basis for assigning single-site mutant flavodoxins and for correlating structural differences between wild-type and mutant flavodoxins with altered redox potentials. PMID- 8477185 TI - Sequence-specific 1H and 15N resonance assignments and secondary structure of GDP bound human c-Ha-Ras protein in solution. AB - All the backbone 1H and 15N magnetic resonances (except for Pro residues) of the GDP-bound form of a truncated human c-Ha-ras proto-oncogene product (171 amino acid residues, the Ras protein) were assigned by 15N-edited two-dimensional NMR experiments on selectively 15N-labeled Ras proteins in combination with three dimensional NMR experiments on the uniformly 15N-labeled protein. The sequence specific assignments were made on the basis of the nuclear Overhauser effect (NOE) connectivities of amide protons with preceding amide and/or C alpha protons. In addition to sequential NOEs, vicinal spin coupling constants for amide protons and C alpha protons and deuterium exchange rates of amide protons were used to characterize the secondary structure of the GDP-bound Ras protein; six beta stands and five helices were identified and the topology of these elements was determined. The secondary structure of the Ras protein in solution was mainly consistent with that in crystal as determined by X-ray analyses. The deuterium exchange rates of amide protons were examined to elucidate the dynamic properties of the secondary structure elements of the Ras protein in solution. In solution, the beta-sheet structure in the Ras protein is rigid, while the second helix (A66-R73) is much more flexible, and the first and fifth helices (S17-124 and V152-L171) are more rigid than other helices. Secondary structure elements at or near the ends of the effector-region loop were found to be much more flexible in solution than in the crystalline state. PMID- 8477186 TI - Amino acid type determination in the sequential assignment procedure of uniformly 13C/15N-enriched proteins. AB - Experiments and procedures are described that greatly alleviate the sequential assignment process of uniformly 13C/15N-enriched proteins by determining the type of amino acid from experiments that correlate side chain with backbone amide resonances. A recently proposed 3D NMR experiment, CBCA(CO)NH, correlates C alpha and C beta resonances to the backbone amide 1H and 15N resonances of the next residue (Grzesiek, S. and Bax, A. (1992) J. Am. Chem. Soc., 114, 6291-6293). An extension of this experiment is described which correlates the proton H beta and H alpha resonances to the amide 1H and 15N resonances of the next amino acid, and a detailed product operator description is given. A simple 2D-edited constant time HSQC experiment is described which rapidly identifies H beta and C beta resonances of aromatic or Asn/Asp residues. The extent to which combined knowledge of the C alpha and C beta chemical shift values determines the amino acid type is investigated, and it is demonstrated that the combined C alpha and C beta chemical shifts of three or four adjacent residues usually are sufficient for defining a unique position in the protein sequence. PMID- 8477187 TI - A general method for assigning NMR spectra of denatured proteins using 3D HC(CO)NH-TOCSY triple resonance experiments. AB - A general approach for assigning the resonances of uniformly 15N- and 13C-labeled proteins in their unfolded state is presented. The assignment approach takes advantage of the spectral dispersion of the amide nitrogen chemical shifts in denatured proteins by correlating side chain and backbone carbon and proton frequencies with the amide resonances of the same and adjacent residues. The 1H resonances of the individual amino acid spin systems are correlated with their intraresidue amide in a 3D 15N-edited 1H,1H-TOCSY-HSQC experiment, which allows the spin systems to be assigned to amino acid type. The spin systems are then linked to the adjacent i-1 spin system using the 3D H(C)(CO)NH-TOCSY experiment. Complete 13C assignments are obtained from the 3D (H)C(CO)NH-TOCSY experiment. Unlike other methods for assigning denatured proteins, this approach does not require previous knowledge of the native state assignments or specific interconversion rates between the native and denatured forms. The strategy is demonstrated by assigning the 1H, 13C, and 15N resonances of the FK506 binding protein denatured in 6.3 M urea. PMID- 8477188 TI - Contributions from hydration of carboxylate groups to the spectrum of water polypeptide proton-proton Overhauser effects in aqueous solution. AB - Nuclear Overhauser effects (NOE) were measured between water protons and protons of the glutamic acid side chain of the bicyclic decapeptide c-[Arg-Arg-Cys-Asn Ala-Glu-Ala-Cys-Lys-Gly] in aqueous solution. Positive NOEs were observed between the gamma CH2 group of Glu and the water resonance, with similar NOE intensities at pH 2.0 and pH 6.3 in both the laboratory frame and the rotating frame of reference. These results indicate that the residence times of the hydration water molecules near the side-chain methylene protons are shorter than 500 ps for both the charged form and the uncharged form of Glu, and hence comparable to the water residence times near uncharged amino acid side chains. Furthermore, this study shows that the acidic proton in protonated carboxylic acid groups is not likely to interfere with the observation of polypeptide-hydration water NOEs, which is in contrast to the hydroxyl protons of the side chains of serine, threonine and tyrosine. PMID- 8477189 TI - Detection of gene rearrangements in reactive lymphoid processes. AB - We report the immunohistologic and the genotypic analysis of lymph node biopsies from 23 cases of reactive processes, and two cases of atypical lymphoproliferations (AL). Clonal gene rearrangements were detected in 5 cases of proven reactive processes as well as in both AL, in which no signs of malignancy were detected during the phenotypic analysis. No patient, apart from the two AL cases, showed any progression to malignancy during a follow-up period of 28-43 months after the initial biopsy. PMID- 8477190 TI - Long-term treatment of chronic myelogenous leukemia with different interferons: results from three studies. AB - 131 patients with Philadelphia (Ph') chromosome positive chronic myelogenous leukemia (CML) were treated with interferon (IFN) alpha or a combination of IFN alpha and IFN gamma. In study, 1, 13 not pretreated and 41 pretreated patients, 48 in chronic phase disease, 6 in accelerated phase, received 4 x 10(6) U/m2 IFN alfa-2b initially. After achievement of hematologic remission, the individually minimum effective dose was used for maintenance. There was no response in acute phase disease. Of the 48 patients with chronic phase disease, 22 achieved a hematologic remission (HR), 13 a partial HR (PHR), and 13 did not respond (NR) to IFN. No major cytogenetic response occurred in these patients, but two patients achieved a major molecular response in Southern blots, whereas PCR tests were positive. In a further randomized study, CML patients without prior therapy were treated initially with 4 x 10(6) U/m2 IFN alpha alone (arm A) or in combination with 50 micrograms IFN gamma (arm B). For maintenance, the maximum tolerable dose of IFN alpha was given (up to 10 x 10(6) U/day). Thirteen patients in arm A (54%) and 14 (56%) patients in arm B achieved a HR, 7 patients (29%) in arm A and 6 patients (24%) in arm B a PHR. No response could be induced in 4 patients (17%) of arm A and 5 patients (21%) of arm B. Major cytogenetic responses were observed in 5 (20%) patients of arm A and 5 patients (20%) of arm B. Major molecular responses were observed in 3 patients of arm A and 5 patients of arm B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477191 TI - Increased risk of neurological relapse in acute lymphoblastic leukemias with high levels of cerebrospinal fluid thymidine kinase at diagnosis. AB - Cerebrospinal fluid thymidine kinase (CSF-TK) was measured at diagnosis in 62 patients with acute lymphoblastic leukemia (ALL) without initial neurological manifestations, who achieved a complete remission after chemotherapy. During the follow-up period, 10 patients developed central nervous system (CNS) involvement. At the onset of the disease mean CSF-TK levels in these subjects were found to be significantly higher than those observed in patients without subsequent CNS complications. In particular, 7/10 (70%) of these patients who presented CSF-TK levels above the upper limit of normal (1.4 U/microliters) had evidence of a neurological relapse, while 49/52 (94.2%) of subjects with presenting CSF-TK levels of up to 1.4 U/microliters did not develop a neurological leukemic disease (p < 0.00001). The white blood cell count at diagnosis was significantly increased, but not directly correlated to CSF-TK levels, in the group with CNS involvement, while age, serum thymidine kinase levels and lactic dehydrogenase, FAB classification or immunophenotype were not different in patients with or without neurological relapse. In conclusion, increased levels of CSF-TK at presentation correlate with a high risk of subsequent CNS involvement in patients with responsive ALL. PMID- 8477192 TI - Myelomonocytic antigens are rarely expressed on B-lymphocytic leukemia cells. AB - In the light of recent observations reporting that B-lymphocytic leukemia (B-CLL) cells may express a variety of myelomonocytic antigens, 28 patients with B-CLL and B-leukemic lymphocytic lymphoma were studied for the presence of these antigens using monoclonal antibodies to detect CD13, CD33, CD15 and CD14. Analysis of immunofluorescence (IF) was carried out by two procedures; one which employed the standard conventional method of gating used in our laboratory for flow cytometry, while the other procedure increased the sensitivity of the analysis, by moving the marker for IF to the left, so as to widen the gate to include more cells with low IF. Using the conventional methodology, the mean proportion of cells considered positive was less than 3% for any of the 4 markers studied. In only a few patients were 5% or more of the B-CLL cells positive for some of the markers studied (3 patients with 6.2-11.3% CD13+; 2 with 6.0-9.6% CD14+, and one with 11.8% CD15+ cells). No case had more than 2.5% + CD33+ cells. The second procedure with a wider gate to enhance sensitivity for less positive cells, increased the number of positive cells for any of the markers in only 4 patients. These results are contradictory to others reported recently, and some of the possible causes for this discrepancy are discussed. It is suggested that more useful data may be obtained if the level of staining intensity and patterns of positive staining are documented in the future. PMID- 8477193 TI - Functional differences of T cells in B-chronic lymphocytic leukemia. AB - B cell chronic lymphocytic leukemia (B-CLL) is a disease characterized by an accumulation of monoclonal lymphocytes of B cell origin. Although the neoplastic process involves the B lymphocyte compartment, phenotypic and functional defects within the T lymphocyte population implicate their possible role in the pathogenesis of the disease. We analyzed the functional and morphological integrity of T lymphocytes from the peripheral blood of 64 patients with B-CLL. The activation of B-CLL T cells after PHA stimulation was determined by measuring [3H]-thymidine incorporation, assessing cell numbers in parallel cultures, and by monitoring the lymphocyte subsets during 9 days of cultivation. Our results indicate the presence of three functionally different populations of T cells in the peripheral blood of B-CLL patients. We present evidence for an increased proliferative potential of T lymphocytes from a group of patients with B-CLL. PMID- 8477194 TI - Differentiation and growth modulation of myeloid leukemia cells by the protein kinase C activating agent bryostatin-1. AB - Bryostatin-1 (Bryo), a macrocyclic lactone of the sea water bryozoan Bugula neritina, is a potent activator of protein kinase C and was found to exhibit antineoplastic activity in several systems. We studied the effect of Bryo on differentiation and growth modulation of human myeloid leukemia cell lines and freshly explanted blood cells from patients with myeloid leukemia. Alterations at the molecular level and phenotypic changes triggered by Bryo were similar, but not identical, to those induced by phorbol esters. Bryo was able to inhibit cellular proliferation as evidenced by [3H]-thymidine uptake and induced morphological changes associated with monocytic differentiation. In studies using continuous cell lines, the glucocorticoid dexamethasone was unable to prevent the Bryo-induced growth inhibition or the induced phenotypic changes. However, in fresh myeloid blood cells dexamethasone attenuated these Bryo-triggered effects. Our own data taken together with reports from the literature reviewed here suggest the following conclusions: (i) Bryo, while lacking tumor promoting activity, is able to induce differentiation in maturation arrested leukemia cells; (ii) it exhibits selective antiproliferative properties in normal or malignant hematopoietic cells and supports growth of multipotent stem cells. These features might qualify Bryostatin-1 as a potential candidate for promising research and possibly for future clinical applications. PMID- 8477195 TI - Clinical spectrum of autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia. AB - Autoimmune haemolytic anaemia (AIHA) is a frequent complication of chronic lymphocytic leukaemia (CLL). The course of AIHA in CLL is quite variable and unpredictable. We report 9 patients who showed three distinct clinical patterns. Three patients had a single episode of AIHA which responded rapidly to oral prednisolone. Three others had a relapsing course often associated with a rising lymphocyte count which responded to a combination of prednisolone and cytotoxic drugs. The remaining three patients showed very little response to either form of treatment and continued to have haemolytic anaemia for the remainder of their lives. Development of AIHA did not appear to be associated with any particular stage of the disease and only patients with the third type of AIHA seemed to have a short survival. PMID- 8477196 TI - Pure red cell aplasia following ABO mismatched marrow transplantation for chronic lymphocytic leukemia: response to antithymocyte globulin. AB - Pure red cell aplasia was observed in a 28 year old woman following a major ABO mismatched allogeneic bone marrow transplant for chronic lymphocytic leukemia. No evidence of red blood cell production was observed for more than one year following transplant despite the absence of high isohemagglutinin titers. Treatment with antithymocyte globulin resulted in prompt restoration of reticulocytosis. Therapy with antithymocyte globulin should be considered in these instances when red cell aplasia follows mismatched allogeneic marrow transplantation. PMID- 8477197 TI - Serum erythropoietin and circulating BFU-E in patients with multiple myeloma and anaemia but without renal failure. AB - In 30 patients with multiple myeloma (MM) and mild to moderate anaemia (mean Hb 107 g/l, 95% confidence limit (CL) 102-113) but no evidence of renal failure (serum creatinine < 110 mumol/l), serum erythropoietin (EPO) showed significant inverse logarithmic correlation with the haemoglobin level (r = -0.57, p = 0.001). The observed/expected ratio of log-EPO in patients with MM (mean 0.96, CL 0.89-1.04) was similar to that of 119 subjects (mean 1.01, CL 0.96-1.05) with or without anaemia (mean Hb 116 g/L, CL 110-121) but without renal failure. The concentration of circulating erythroid progenitors (BFU-E) in 10 MM patients in plateau phase was significantly reduced (mean 0.70 x 10(5)/l of blood, CL 0.34 1.06) compared to that of 8 normal controls (mean 3.57, CL 1.60-5.55, p = 0.011) In vitro sensitivity of the BFU-E to EPO in the patients with MM was comparable to that of the normal controls. It appears that in MM there is an appropriate EPO response to anaemia but even in the plateau phase the number of circulating BFU-E is reduced, reflecting a degree of marrow failure. However, the progenitors are normally sensitive to EPO in such patients, and therapeutic doses of EPO may correct the anaemia by a pharmacological rather than a physiological effect. PMID- 8477198 TI - Erythroleukemia and myelodysplastic syndromes: an historical appraisal and a personal view. PMID- 8477199 TI - Chronic myelomonocytic leukaemia (CMML)--a myelodysplastic or myeloproliferative syndrome? AB - Chronic myelomonocytic leukaemia (CMML), a disorder belonging to the group of myelodysplastic syndromes, has a number of peculiar features which raise the question as to whether it should be considered a distinct entity in its own right. The problems associated with its classification and diagnosis are discussed in this report using all currently available tools from clinical data to molecular genetics, including morphology, histology, cellular biology and cytogenetics. Three groups of patients can be identified (isolated monocytosis with a mild degree of dysplasia, severe cytopenia and the most frequent type with proliferative symptoms dominating the clinical picture). The latter group is close to atypical chronic myeloid leukaemia and perhaps these two entities should be regarded as a single one. Classification of the disease is further complicated by the possibility of evolution from one subgroup into another one and by the finding that CMML can also arise as a disorder secondary to other myeloproliferative (MPS) or myelodysplastic (MDS) syndromes. No specific marker of the disease has been identified by cytogenetics or molecular biology. Due to all these facts, we believe that CMML should perhaps be viewed more pragmatically by considering the use of prognostic factors that could at least help to define different groups of patients who may require different therapeutic strategies. We conclude that CMML is a heterogeneous syndrome with features of both MPS and MDS, encompassing primary and secondary stem cell disorders and varying widely in its clinical presentation. This heterogeneity should stimulate the search for reliable predictors of evolution which would allow a better definition of CMML subtypes based on prognostic factors. PMID- 8477200 TI - Therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: possible use of interferon on the basis of some novel concepts. AB - Current understanding of molecular genetics enables the establishment of new categories based on pathogenesis. Philadelphia (Ph) chromosome-positive leukemia has been reclassified into two molecularly distinct subsets, and the leukemogenesis at the cell level might be linked to the molecular changes. Therefore, treatment for leukemia patients with Ph chromosome could be based on the molecular characteristics. In this review, we discuss the strategy of treating patients with Ph-positive acute lymphoblastic leukemia and the benefit of the combined modality of interferon and chemotherapy. PMID- 8477201 TI - Myelodysplasia, vasculitis and anti-neutrophil cytoplasm antibodies. AB - A cutaneous or systemic vasculitis occurs in myelodysplasia as well as in myeloproliferative and lymphoproliferative disorders. The most common lesion is a leucocytoclastic vasculitis, with neurological or joint involvement occurring less often. The vasculitis may appear contemporaneously with or precede the clinical onset of the blood dyscrasia. Occasionally the lesions respond dramatically to the use of steroids but in general, patients with vasculitis have a worse prognosis than those with uncomplicated myelodysplasia. Vasculitis and myelodysplasia appear together too often for the association to be coincidental and the vasculitis in most cases cannot be attributed to intercurrent infections, therapeutic agents or a pre-existing rheumatological disorder. While autoantibodies are frequently present in myelodysplasia, and ANA and anti neutrophil cytoplasm antibodies (ANCA) are found in other vasculitides, neither of these antibodies is associated with the vasculitis of myelodysplasia. There has however been one report of ANCA in Sweet's syndrome a non-vasculitic skin condition that also occurs in the myelodysplastic syndromes. PMID- 8477202 TI - Megakaryocytic ploidy in myelodysplastic syndromes. AB - The megakaryocytic ploidy was microfluorometrically measured in 12 normal controls and 15 myelodysplastic syndrome (MDS) patients using DAPI (4',6 diamidino-2-phenylindole) staining after destaining of the Wright-Giemsa (WG) stain. MDS patients had slightly more immature megakaryocytes when compared with normal controls. The megakaryocytic ploidy distribution had a peak at 16N in normal controls, at 8N in the 11 of the 15 MDS patients, and at 4N in the remaining 4 patients, which is suggestive of impaired polyploidization in MDS patients. In MDS, micromegakaryocytes were shown not to be immature but much more impaired in polyploidization than non-micromegakaryocytes. However, there was no difference in the megakaryocytic ploidy pattern among the type of the modification of Feinendegen' classification in each case for both the normal controls and the MDS patients, suggesting that the megakaryocytic ploidy is probably determined at the maturation level of the megakaryoblasts or the precursor cells. The study of megakaryocytic ploidy before and after therapy in the case of refractory anemia with excess of blasts might suggest that the remission of MDS patients might be qualitatively different from that seen in acute leukemia patients. Furthermore, the DNA histogram of the megakaryocytes from one of the two MDS patients obtained by the new method, which is able to determine the amount of DNA in the immunologically identified megakaryocytes microfluorometrically, using the monoclonal anti-glycoproteins IIb/IIIa antibody on bone marrow smears, showed a shift towards small ploidy compared with those defined on the basis of WG staining. This finding indicates that the micromegakaryocytes or the megakaryoblasts which could not be identified morphologically can be identified immunologically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477204 TI - Cisplatin-CBV with autologous bone marrow transplantation for relapsed Hodgkin's disease. AB - The use of high-dose cyclophosphamide, carmustine, and etoposide (CBV) with autologous bone marrow transplantation (ABMT) results in long-term disease-free survival of about 30% in patients with relapsed Hodgkin's disease. Laboratory and clinical data show that cisplatin is synergistic with etoposide and carmustine, with non-overlapping extramedullary toxicity. Twenty-one patients with relapsed Hodgkin's disease that had progressed after both MOPP-like and ABVD-like regimens were treated with CBV plus cisplatin (90 mg/m2) and ABMT. The CR rate was 55%; the three-year disease-free and overall survival were 29% and 38% respectively; these results are comparable to prior experience with CBV. Performance status was strongly correlated with achievement of CR, survival, and time to treatment failure. Nephrotoxicity was seen in 3 patients, and ototoxicity in 1 patient. Although cisplatin could be added to CBV with minimal additional toxicity, the results obtained in this small patient population were not better than those of the earlier regimen. A larger trial in patients not previously exposed to cisplatin may better define the role of its addition to CBV. PMID- 8477203 TI - The rationale of therapy with mitoxantrone in non-Hodgkin's lymphoma. The Non Hodgkin's Lymphoma Co-operative Study Group, (NHLCSG) Italy. AB - In order to evaluate the role of Mitoxantrone in the therapy of non-Hodgkin's lymphoma (NHL) (intermediate-high grade malignancy) a series of successive phase II-III studies were performed in a multicenter cooperative group. The first phase II study consisted of Mitoxantrone alone administered at 14 mg/m2 i.v. on day 1 and repeated every 3 weeks for six times. Fifteen refractory or relapsed patients (pts) entered the study, and an overall response of 54% (CR 4 pts, PR 4 pts) was obtained. 7 pts progressed or remained stable disease (NR). The second phase II consisted of Mitoxantrone in combination with Etoposide and Prednisone (VeMP). Twenty pts were treated and a complete remission (CR) of 50% with 1 partial remission (PR) were obtained with an overall response of 55%. The third phase II study consisted of 13 pts with refractory or relapsed disease treated with Mitoxantrone, Cis-platinum, Etoposide and Prednisone (CEMP); an overall response of 62% was obtained with an acceptable toxicity. This was not superior to other conventional salvage regimens. On this background a phase III study with VEMP (Etoposide, Cyclophosphamide, Mitoxantrone, Prednisone) was started as first line therapy for pts presenting one or more of following criteria: Performance Status (P.S.) 2-3, aggressive histology at stage I-IIE or advanced stage in old pts, low grade histology with B-symptoms stage in III-IV, age over 65 years. Until now 64 pts entered this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477205 TI - Is recombinant human erythropoietin treatment in myelodysplastic syndromes worthwhile? AB - It has been recently demonstrated that erythropoietin increases the haemoglobin levels in anemia secondary to chronic renal failure. Moreover some recent experiences also suggested a possible role in the treatment of MDS. From April 1990 to April 1992, 23 patients (16 males and 7 females, median age 63.5 years) affected with low risk myelodysplastic syndrome (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and transfusional requirement. All patients received high doses of rHuEPO (800 U/Kg weekly s.c. in 2-3 divided doses, for 3 months). A complete remission, defined as stable normalization of Hb level, was achieved in 1/23 patients. This patient had refractory anemia, by FAB criteria. A partial response, defined as stable increase of Hb levels > or = 1 g/dl and/or reduction of transfusional requirement > or = 50% lasting at least 3 months, was achieved in 7/23 patients. Patients with a partial response received rHuEPO at increased dosages (1200 U/Kg weekly s.c. 2-3 times): 1/7 achieved a complete response, 4/7 remained stable and 2/7 decreased to pre-therapy Hb value. These results suggest that rHuEPO may be a promising therapeutic tool for some MDS patients. PMID- 8477206 TI - Host tumor infiltrating lymphocytes in B cell non-Hodgkin's lymphomas. AB - Tumor-infiltrating T lymphocytes (TIL-T) were quantitated by three color flow cytometry in cell suspensions from excisional biopsy specimens of 43 B cell non Hodgkin's lymphomas (NHL) and 8 benign lymphoid hyperplasias (BLH) to identify potential differences in host T cell responses. We quantitated three TIL-T subsets: CD3+CD4+CD8- (helper-inducer), CD3+CD4-CD8+ (suppressor-cytotoxic) and CD3+CD25-HLADr+ (long term activated TIL-T) and compared them in three diagnostic groups: BLH, low grade B cell NHL (LG NHL) and intermediate-high grade B cell NHL (IG-HG NHL). The following results were obtained: Mean percentage +/- s.e. of activated TIL-T for BLH, LG-NHL and IG-HG NHL: 10.3 +/- 1.9, 23.2 +/- 4.6 and 38.8 +/- 9.5, respectively. Mean percentage +/- s.e. of suppressor-cytotoxic TIL T for same groups: 13.9 +/- 1.5, 14.9 +/- 1.9 and 34.4 +/- 4.5, respectively. Mean percentage +/- s.e. of helper-inducer TIL-T cells for the same groups was 38.2 +/- 12.7, 32.1 +/- 7.2 and 22.5 +/- 4.6, respectively. Helper/suppressor ratio +/- s.e. for same groups was 3.0 +/- 1.1, 2.4 +/- 0.6 and 1.3 +/- 0.4, respectively. Activated and suppressor-cytotoxic TIL-T percentage progressively increased from BLH toward IG-HG NHL. The percentage of these two TIL-T subsets were significantly higher in IG-HG NHL than in BLH and LG-NHL (P < 0.0007, 0.0002, 0.0001 and 0.0260 for the comparisons TIL-T in BLH vs IG-HG NHL and LG NHL vs IG-HG respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477207 TI - Cytolytic (TIA-1+) tumor infiltrating lymphocytes in B cell non-Hodgkin's lymphomas. SWOG Central Repository Members. AB - TIA-1 is a monoclonal antibody (mAb) that identifies cytolytic cells. We studied eleven B cell non-Hodgkin's lymphomas (NHL) of low grade, eleven B cell NHL of intermediate-high grade, and 10 benign lymphoid hyperplasias (BLH) to investigate potential differences in the number of host cytolytic tumor infiltrating lymphocytes (TILs). Frozen sections were immunostained with TIA-1 mAb and the number of immunoreactive cells (TIA-1+) per mm2 of tissue was quantitated within reactive or neoplastic lymphoid follicles or random areas of diffuse NHL. The number of TIA-1+ cells/mm2 was significantly higher in intermediate and high grade B cell NHL than in low grade NHL or BLH with means +/- se of 1377.8 +/- 173, 866.2 +/- 92.3 and 774.1 +/- 76.2, respectively (p < 0.0183 and p < 0.0125). There was no significant difference between BLH and low grade NHL. The increased number of TIA-1+ TILs in B cell NHL of intermediate and high grade suggests the possibility of a host cytolytic immune response versus the tumor. Paradoxically, B cell tumors of worst biological outcome contained more cytolytic TILs. Functional defects of host cytolytic TILs in NHL patients should be investigated in future studies. PMID- 8477208 TI - Treatment of extrahepatic portal venous obstruction. PMID- 8477209 TI - Amphotericin B in resistant kala-azar in Bihar. AB - BACKGROUND: During the recent epidemic of kala-azar in Bihar, we identified a group of patients who were unresponsive to the two commonly used drugs--sodium stibogluconate and pentamidine. We evaluated the use of amphotericin B in these patients because it has been shown to be active in experimental animals against amastigotes and promastigotes, it has been found to be useful in South American patients and is now recommended by the World Health Organization as a second line drug. METHODS: We selected 300 patients who were unresponsive to sodium stibogluconate and pentamidine (out of 500 patients with kala-azar confirmed by demonstration of Leishmania donovani bodies in their splenic aspirates). Amphotericin B was given in a dose of 1 mg/kg body weight on alternate days starting with 0.05 mg/kg body weight with daily increments till a 1 mg dose was reached. A total dose of 20 mg/kg was given initially and repeated if the parasites persisted. The investigations done before and after treatment were splenic or bone marrow aspiration, measurement of the spleen and liver size, body weight, total and differential white cell counts, haemoglobin level, total serum protein, blood urea, serum creatinine, serum potassium, blood sugar, serum alanine and aspartate transaminase, electrocardiography and a chest X-ray. The efficacy of treatment was assessed at the end of treatment and after 6 months of follow up. RESULTS: After treatment with amphotericin B, 298 (99%) of the patients had been cured of their disease as evidenced by the disappearance of fever, reduction of hepatosplenomegaly, clearance of the parasites from the spleen and bone marrow and an absence of relapse on 6 months of follow up. Two hundred and sixty-eight (89%) patients required 1 g of the drug, 24 (8%) required 1.5 g and 6 (2%) required 2 g. All patients had shivering and fever during the infusion. Two had a cardiac arrest from which they could not be revived. Other complications included anorexia, stomatitis, jaundice, hypokalaemia and a rise in blood urea. However, these were only mild and improved after treatment was stopped. CONCLUSION: Amphotericin B is an effective drug for patients with kala azar unresponsive to treatment with sodium stibogluconate and pentamidine, but it should be administered under close medical supervision. PMID- 8477210 TI - Community health awareness among recent medical graduates of Bombay. AB - BACKGROUND: Since Independence in 1947, the need for reorientation of our western style, hospital-based, urban-oriented medical education has been well recognized and much discussed but little action has been taken to make it more community based. Against a background of 40 years of debate, we conducted a study of 342 medical graduates commencing their internship training in one government and two municipal medical colleges to assess the effects of medical education on them. METHODS: A questionnaire was administered to examine recent interns' awareness of some aspects of community health, their perceptions of the concept of Primary Health Care and their knowledge of rational prescriptions for minor ailments and for major illnesses of public health importance. RESULTS: We found a lack of basic health information among recent medical graduates, an apathy towards matters of public health importance, and gaps in their knowledge of curative care and rational prescribing. CONCLUSION: We suggest that there is a need not only to effect changes in the curriculum but also to assess whether these changes might lead to the making of doctors more suited to work in our villages. PMID- 8477211 TI - Tropical pulmonary eosinophilia in an Orissa village. AB - BACKGROUND: Tropical pulmonary eosinophilia is usually seen in areas endemic for filariasis. It affects only a small proportion of the population at risk and microfilaria are rarely demonstrated in the peripheral blood. The actual prevalence of the tropical pulmonary eosinophilia syndrome has not been previously studied in an area endemic for filariasis. METHODS: We screened the population of a village in the Puri district of Orissa, where filarial infection is endemic, to determine the prevalence of tropical pulmonary eosinophilia by clinical examination measuring the absolute eosinophil counts, performing a chest X-ray and examining the stools for the presence of the parasite. Sera from symptomatic cases who had an eosinophil count above 2000 per cmm were further tested for filarial specific IgG and total IgE and the results compared with control sera obtained from 15 age- and sex-matched normal individuals. RESULTS: We were able to screen 1754 (91%) out of 1918 villagers who were more than 5 years old and found 69 cases who had typical clinical features of tropical pulmonary eosinophilia. Only 6 (0.34%) of these had eosinophil counts above 3000 per cmm and were considered to have the disease. Only 2 of the 6 had associated filarial lesions, one had microfilaraemia and 3 had typical chest X-ray changes. The mean (+/- SD) titres for filaria specific IgG (0.355 +/- 0.315 v. 0.120 +/- 0.092) and total IgE (0.455 +/- 0.316 v. 0.114 +/- 0.075) were significantly higher in cases with tropical pulmonary eosinophilia than in control subjects. The level of eosinophilia was related neither to the patients' immune status nor to the severity of the radiological lesions. All cases recovered after therapy with diethylcarbamazine. CONCLUSION: Tropical pulmonary eosinophilia is not uncommon in this community in Orissa where filariasis is endemic. However, the syndrome is rarely associated with clinical filarial lesions. PMID- 8477212 TI - Antibiotics in febrile neutropenia: a randomized prospective comparison of two combinations. AB - BACKGROUND: Problems of initial empirical antibiotic therapy in febrile neutropenia are further complicated by other factors such as cost and the pattern of infective organisms in a particular institution. We, therefore, conducted a randomized study comparing the efficacy of two sets of antibiotics which differed in their spectrum of action, availability and price. METHODS: Sixty episodes of febrile neutropenia in 40 patients who were not on any prophylactic antibiotics were randomized into one of two arms--cefotaxime and gentamicin or ciprofloxacin and gentamicin. Depending upon the response by 72 hours, they were crossed over to the other arm or continued with the same combination. Empirical antifungal therapy was added in those who did not become afebrile. RESULTS: Infection was documented either clinically, bacteriologically or radiologically in 42% of the febrile episodes. The commonest organism isolated was Klebsiella and the commonest organism producing bacteraemia was the Staphylococcus. The temperature was reduced to normal without cross-over in 53% of the febrile episodes with cefotaxime and gentamicin and in 60% with ciprofloxacin and gentamicin (p > 0.05). After cross-over the temperature came down in 30% of the episodes with cefotaxime and gentamicin (initial combination) and 40% with ciprofloxacin and gentamicin (initial combination; p > 0.05). The overall response rate without empirical antifungal therapy was 83% in the patients on cefotaxime and gentamicin (initial combination; p > 0.05). While both the arms of the study had a 100% response rate, there was no significant difference between the efficacy of the antibiotic combinations. The ciprofloxacin-gentamicin combination is one-third as expensive as cefotaxime-gentamicin and is more readily available. CONCLUSION: We recommend the use of ciprofloxacin and gentamicin as the initial drug combination and cefotaxime and gentamicin only when the former is not effective. PMID- 8477213 TI - The immunohistochemistry of solid tumours: potential problems for new laboratories. AB - Immunohistochemistry has become an important tool for tumour typing and has the potential to improve the histopathological diagnosis of neoplasms. However, the large number of publications on the different aspects of the technology are often contradictory. In many instances the immunochemical reactions may not be reproducible and can create problems in the diagnosis of certain tumours. The use of optimal materials and techniques enhance the sensitivity, specificity and reproducibility of these methods. In this article we discuss the common problems of tissue preparation, and antigenic variation, distribution and presentation. However, immunopathological diagnosis has to be accompanied by an in-depth and fundamental understanding of basic immunochemistry and diagnostic immunohistochemistry has to be interpreted in the context of a standard clinical and histopathological examination. PMID- 8477214 TI - Inhaled corticosteroids in childhood bronchial asthma. PMID- 8477215 TI - Standard-dose and high-dose epinephrine in cardiac arrest. PMID- 8477216 TI - 'Cannabis-induced psychosis' may obscure paranoid schizophrenia. PMID- 8477217 TI - Adverse drug interactions. PMID- 8477218 TI - The bioavailability of drugs. PMID- 8477219 TI - The Maharashtra Medical Council. PMID- 8477220 TI - Letter from Ethiopia. PMID- 8477221 TI - Organ transplants: time to buy and sell? PMID- 8477222 TI - Letter from Glasgow. PMID- 8477223 TI - The transplantation of human organs bill 1992. PMID- 8477224 TI - Scientific dishonesty in Indian Biomedical Research. PMID- 8477225 TI - Supreme court judgment on self-financing colleges. PMID- 8477226 TI - Prejudice against reservation. PMID- 8477227 TI - The tragedy of needless pain. PMID- 8477228 TI - Observing the brachial artery through a pressure cuff. AB - A technique is described which enables ultrasonic imaging of the brachial artery whilst pressure is applied via a pressure cuff. This involves a new instrument--a sphygmomanometer, which uses water as opposed to air as the pressure medium, in order to permit ultrasonic imaging through the cuff. The technique was found to be acceptable in the clinical setting, and gave a measurement of the systolic blood pressure which correlated with the conventional cuff measurement in eleven elderly subjects (r = 0.89, p < 0.001). The technique should have an important role to play in studying the origin of differences which occur between direct and indirect blood pressure measurements. PMID- 8477229 TI - Development of a neural network screening aid for diagnosing lower limb peripheral vascular disease from photoelectric plethysmography pulse waveforms. AB - An artificial neural network (ANN) was trained to classify photoelectric plethysmographic (PPG) pulse waveforms for the diagnosis of lower limb peripheral vascular disease (PVD). PPG pulses from the lower limbs, and pre- and post exercise Doppler ultrasound ankle to brachial systolic blood pressure ratio measurements were obtained from patients referred to a vascular investigation laboratory. A single PPG pulse from the big toe of each leg was processed and normalized, and used as input data to the ANN. The ANN outputs represented the diagnostic classifications (normal, significant PVD and major PVD) and the ANN was trained with the ankle to brachial pressure indices (ABPI). The ANN structure consisted of an input layer (50 neuron units from the PPG pulse input), a single hidden layer (15 neurons) and an output layer (3 neurons for the PVD diagnoses). The back-propagation learning algorithm was used to train the ANN for 500 epochs with a PPG training set of pulses from 100 legs. Test data for network assessment comprised pulses from a further 50 legs (20 normal and 30 PVD, of which 15 were categorized as having major disease). A network sensitivity of 93% and specificity of 85% was achieved with respect to the Doppler ABPI standard, giving a diagnostic accuracy of 90%. The results of this study indicate that a neural network can be trained to distinguish between PPG pulses from normal and diseased lower limb arteries. The simplicity of PPG measurement and neural network classification holds promise for the screening of lower limb arterial PVD. PMID- 8477230 TI - A comparison of methods for estimating left ventricular volumes from radionuclide ventriculography. AB - An accurate reproducible measurement of left ventricular volume is important in the evaluation of cardiac disease. Four methods of left ventricular volume measurement by radionuclide ventriculography have been compared and their reproducibility assessed in a patient group. The methods studied were a geometric method, a method based on count data alone and two methods which require a blood sample and an estimate of ventricular depth. The accuracy of absolute volumes is difficult to determine due to the lack of a 'gold standard'. The method using count data alone was found to give reproducible results. Volumes can be calculated quickly and easily from data acquired in a standard radionuclide ventriculogram. End systolic volumes calculated using this method clearly separated normal and abnormal patient groups. PMID- 8477231 TI - A system for monitoring temperature distribution in bed and its application to the assessment of body movement. AB - For the assessment of body movements during sleep, a system for monitoring the temperature in bed was developed. The system consists of 16 temperature sensors and a data logger with a memory card. Fifteen of the temperature sensors were arranged in line 6 cm apart on a flat cable. The temperatures at these 15 points in the bed, and the room temperature measured by the additional sensor, were stored on the memory card at predetermined intervals. The data were transferred into a microcomputer and analysed. Changes in posture and body movement were recognizable from the changes in the temperature profile, and well visualized using a three-dimensional display of the successive temperature profiles in the bed. The time of body movement was estimated from the derivative of the temperature profile. Comparison between this estimation and the video recording showed good agreement. The linear arrangement of the sensors provides a high resolution temperature profile during sleep. PMID- 8477232 TI - Digital fundus imaging using a scanning laser ophthalmoscope. AB - While many systemic diseases have ophthalmic manifestations with visible pathological features affecting the fundus, diabetic eye disease is of particular interest. There are many advantages in using digital image analysis to quantify the extent of retinal pathology in diabetes particularly to monitor its progression. However, the usual method of imaging involves photographing the retina using a fundus camera. Not only does this require that the photographs be digitized prior to analysis, but the resulting illumination across the image is non-uniform and this creates problems in digital image analysis. This paper describes the construction of a scanning laser ophthalmoscope interfaced to a computer, which has a number of significant advantages for digital retinal imaging. Firstly, it has better uniformity of illumination than the fundus camera and operates at much lower light levels. Secondly, it permits imaging at various wavelengths with no consequent degradation in image quality; in particular, the value of imaging at infrared wavelengths to give greater tissue penetration is demonstrated. Finally, by introducing the capability for confocal imaging, tomographic images can be taken, improving the perceptibility of features situated deep in the retina. Typical images are shown to demonstrate the potential of this instrument. PMID- 8477233 TI - Review of seven cardiac electrophysiology stimulators. AB - Seven cardiac electrophysiology stimulators from four manufacturers (Biotronik, Bloom, Digitimer and Medtronic) in common current use are reviewed. The stimulators differ in the features provided and the design adopted to achieve these features. The number of output channels ranges from one to four, the number of extra-stimuli available ranges from two to six, and these can be delivered as a variety of sequences. Some of the stimulators (Digitimer and Bloom) are modular while others (Biotronik and Medtronic 532 series) are of an integrated design comprising a single physical unit. The design of the Medtronic EP-2 has both integrated and modular characteristics. The features of the stimulators associated with input, output, control and the user interface are specifically reviewed. The features are also compared against the published recommendations of the American Heart Association. In addition, a summary of stimulator user comments from a number of electrophysiology centres is presented. All of the stimulators fulfil, or are close to fulfilling, basic electrophysiological requirements, but some provide more complex facilities such as would be required by specialist centres. PMID- 8477234 TI - The direct measurement of glomerular filtration rate from the continuous monitoring of DTPA clearance. AB - A method of measuring glomerular filtration rate is proposed, intended for use during gamma camera renography and involving the continuous monitoring of DTPA activity in blood, a single blood sample, and a urine collection. Data obtained from experiments using a CsI scintillation detector are presented and used to demonstrate the validity of the method. In a comparison with a direct measurement of renal clearance of DTPA the proposed method showed an average overestimate of 13% compared to an overestimate of 30% for an uncorrected single-compartment model calculation of filtration rate. Some limited data using a gamma camera to monitor the DTPA activity in blood are also presented. PMID- 8477235 TI - [Migration of cells from neocortical transplants]. PMID- 8477236 TI - [Preliminary results in the use of the binemic structure of human chromosomes]. PMID- 8477237 TI - [Primary structure of the triple block RNA genes of the Plantago asiatica mosaic virus]. PMID- 8477238 TI - [A phototested chemical sensor element based on a field transistor]. PMID- 8477239 TI - The magic of surgery. PMID- 8477240 TI - Intraoperative evoked potentials: an overview. AB - Over the past decade the application of neurophysiologic monitoring techniques has been a major factor in decreasing the incidence of neurologic dysfunction following orthopedic, vascular, and neurosurgical operations. This article focuses on the common neurophysiologic monitoring modalities and their basic intraoperative applications. PMID- 8477241 TI - Use of vasoconstrictors in anesthesia. AB - The increased use of local anesthetic procedures in the busy operating room (OR) environment both within a hospital setting and for outpatient procedures has made it increasingly important for all those who provide health care during the perioperative period to become familiar with these local anesthetic agents. The use of vasoconstrictor agents in combination with local anesthetic solutions is discussed, including their pharmacology, dosage, side effects, and contraindications to their use. Also noted are important anesthetic drug interactions with vasoconstrictor agents as they are used in combination with local anesthesia and general anesthetic agents. PMID- 8477242 TI - Regional anesthesia: considerations for the perioperative nurse. AB - Recent literature suggests that regional anesthesia can improve outcome and decrease hospital stay and costs. Through a better understanding of regional anesthesia, the perioperative nurse specialist can be an invaluable asset to both the patient and anesthesiologist. This article discusses the indications and limitations of the more common regional anesthetic techniques. PMID- 8477243 TI - Anesthetic considerations for neonatal and infant patients. AB - Selected topics in anesthesia that are intended to assist the perioperative nurse in caring for the neonate and infant during surgery are addressed in this article. Issues discussed include airway management, physiological differences between infants and adults, fluid management, and monitoring. PMID- 8477244 TI - Malignant hyperthermia: perioperative considerations. AB - In no situation is perioperative patient advocacy more important than when a smoothly running case is interrupted by an episode of malignant hyperthermia (MH). An understanding of the demographics, manifestations, and clinical interventions can enable the perioperative nurse to respond in an appropriate manner. PMID- 8477245 TI - General anesthesia: what the perioperative nurse needs to know. AB - General anesthesia represents a critical experience for the surgical patient. The implications of general anesthesia for perioperative nursing care are extensive and complex. The surgical patient's needs require the perioperative nurse to possess knowledge of the basic principles of general anesthesia and its complications. PMID- 8477246 TI - Conscious sedation: implications for perioperative nursing practice. AB - Administration of intravenous conscious sedation is one of the many issues facing perioperative nurses. This article explains in detail the implications conscious sedation holds for perioperative nurses. Topics covered include the use of pharmacological agents, nonpharmacological interventions, and acquisition of monitoring skills. PMID- 8477247 TI - Assistive personnel in the perioperative setting: changing the paradigm. PMID- 8477248 TI - Anesthesia pharmacology for general endotracheal anesthesia. AB - The multiple of pharmacological agents and the proliferation of new anesthetic drugs make it incumbent on the perioperative nurse to keep abreast of those areas of pharmacology that impact on their care of the surgical patient. This article provides relevant information about agents used in a general anesthetic technique. Included is the pharmacodynamics of induction agents, skeletal muscle relaxants, inhalation agents, and opioids. PMID- 8477249 TI - My orthopedic mentor. PMID- 8477250 TI - Industry's contribution to quality orthopedic care. AB - The orthopedic industry complies with strict manufacturing standards when producing orthopedic implants. Adherence to these standards assures the surgeon, nurse, and patient of the highest quality implants both in their material composition and in their manufacturing processes so that the maximum benefit can be achieved from the surgical procedure. PMID- 8477251 TI - Infection prevention and management in orthopedic surgery. AB - With all the technological advances made in orthopedic surgery over the years, infection remains the most prevalent postoperative complication. Nationwide figures from the American College of Surgeons demonstrate an infection rate in orthopedic surgery between 5% and 7% for clean cases. The minimum infection rate is 1%. The important principle to remember is that there is no substitute for strict adherence to standard, well-known aseptic surgical techniques for all surgical procedures. PMID- 8477252 TI - Postoperative care of the orthopedic patient. PMID- 8477253 TI - Malignancies of the musculoskeletal system. AB - Malignant bone tumors (sarcomas) are uncommon but diverse in presentation and biological behavior. Major advances in diagnostic imaging, histologic evaluation, operative strategies, and adjuvant therapies have contributed to limb-sparing surgical procedures and improved patient survival rates. PMID- 8477254 TI - Sports medicine: anterior cruciate ligament injuries. AB - Newer techniques in anterior cruciate ligament surgery and accelerated rehabilitation has significantly altered the recovery process as well as the degree of functional recovery and the long-term prognosis. In most cases full recovery can be expected within 6 to 12 months following injury. Although great emphasis is placed on rapid progress in physical therapy and rehabilitation, it is also important to provide the necessary emotional support during this period of disability and altered functional state. PMID- 8477255 TI - The shoulder: common clinical problems. AB - The diagnosis and management of shoulder pain presents a challenge to health care professionals. Shoulder problems affect the quality of life for many people by impacting on activities of daily living and on job performance. For these people a variety of treatment modalities, including surgery, exist. This article presents an overview of common shoulder problems and some of the nonsurgical and surgical treatment modalities that can be used to relieve these problems. PMID- 8477256 TI - Laser applications in orthopedics. AB - The use of lasers has made a significant impact on surgery. Various types of lasers are available for use in orthopedics. A successful laser program identifies perioperative considerations, applications/modalities, and reimbursement issues. As this technology expands, more clinical applications will be utilized. PMID- 8477257 TI - Recovery and banking: allograft bone. AB - Orthopedic surgeries often require bone grafts to replace lost bone. When using the patients own bone is not an option--by choice or dictated by the type or quantity of preferred graft material--bone from a tissue bank may be the answer. A call is made and the order is placed. However, bone grafts are not manufactured like metal implants; they were once a part of a living human being. This article explains the special role tissue banks perform in providing bone and connective tissue grafts. PMID- 8477258 TI - Standardization and management of orthopedic implants. AB - Because the price of orthopedic implants has soared to astronomical heights, and insurance companies are paying less for surgical procedures, institutions must find ways of decreasing their costs and reducing their overhead. In the operating room the orthopedic nurse manager can be instrumental in reducing the amount of implant inventory by collecting and reporting data concerning shelf life of implants and coordinating new product trials and evaluation periods to decrease the number of implant systems to one or two. PMID- 8477259 TI - Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene. AB - Type I (tyrosinase related) oculocutaneous albinism (OCA) results from mutations of the tyrosinase gene on chromosome 11q that lead to reduced or absent melanin pigment synthesis. The phenotype of Type I OCA is broad, ranging from a total lack to only a moderate reduction of melanin, and the phenotypic variation is associated with different mutant alleles at the tyrosinase locus. A total of 36 mutations have been identified in Type I OCA including 24 missense, 4 nonsense, and 8 frameshift mutations. The majority of affected individuals have been compound heterozygotes with different maternal and paternal alleles. Six polymorphic sites for haplotype analysis have been identified in the tyrosinase gene including 2 in the promoter region, 2 in the coding region associated with alternative amino acids in the protein, and 2 RFLPs in the first intron. PMID- 8477260 TI - Detection of more than 94% cystic fibrosis mutations in a sample of Belgian population and identification of four novel mutations. AB - We have analysed 194 Belgian CF chromosomes using a variety of techniques: delta F508 was detected by polyacrylamide gel electrophoresis; dot blotting of PCR products was used to identify the mutations G542X, 1717-1 G-->A, and N1303K; molecular defects in exons 2, 3, 4, 5, 6b, 7, 11, 12, 13, 14a, 14b, 17b, 19, 20, and 21 were screened for by DGGE. We identified 17 mutations, which accounted for 94.3% of the Belgian CF chromosomes. Four novel mutations and a novel polymorphism were characterized. The detection of such a high proportion of Belgian CF mutations is important in understanding the functional role of the molecule and in improving prenatal and genetic diagnosis of CF. PMID- 8477261 TI - Temperature sensitivity of aberrant RNA splicing with a mutation in the G+5 position of intron 37 of the gene for type III procollagen from a patient with Ehlers-Danlos syndrome type IV. AB - A single-base mutation in intron 37 of the gene for type III procollagen (COL3A1) was found in a proband with the type IV variant of Ehlers-Danlos syndrome. Probe protection experiments with S1 nuclease and RNA from fibroblasts incubated at 37 degrees C demonstrated that about 35% of the total mRNA or about 70% of the mRNA from mutated allele was spliced by exon skipping. The effects of the mutation were temperature-sensitive in that the amount of RNA from the mutated allele that was spliced by exon skipping was 87.1 +/- 7.7% at 31 degrees C, 70.1 +/- 6.5% at 37 degrees C, and 85.4 +/- 11.1% at 42 degrees C. The effects of temperature on aberrant RNA splicing were, therefore, the reverse of those reported for four previous mutants in collagen genes. The increase in abnormal RNA splicing when the temperature was raised from 31 degrees to 37 degrees C seen with previously reported mutants suggested that RNA-RNA hybridization of U1snRNA to the 5'-splice site in the substrate may be limiting in the processing of transcripts from the mutated alleles, since RNA-RNA hybridizations become less favorable at higher temperatures. The decrease in abnormal RNA splicing seen here when the temperature was raised from 31 degrees to 37 degrees C suggested that protein-RNA or protein-protein binding steps become rate limiting with the G+5 mutation in intron 37 of the COL3A1 gene. PMID- 8477262 TI - Identification of mutations in Danish choroideremia families. AB - We have searched for mutations in the choroideremia gene (CHM) in patients from 12 Danish families in which CHM is segregating. Employing polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing, different mutations have been identified in 6 patients. All the mutations will interfere with the correct translation of the mRNA predicting a truncated protein or no gene product at all. PMID- 8477263 TI - Molecular characterization of beta-thalassemia in Egyptians. AB - We sought to determine the spectrum of mutations producing beta-thalassemia in Egypt using genomic PCR and a variety of mutation-screening procedures. Thirty four beta-thalassemia and three Hb S/beta-thalassemia patients originating from different regions of Egypt were studied, and the causative mutation was found in 69 of 71 (97%) beta-thalassemia genes. Four mutations accounted for 78% of beta thalassemia genes in this population; IVS-1, nt 110 (41%), IVS-1 nt 6 (13%), IVS 1, nt 1 (13%), and IVS-2, nt 848 (11%). The latter allele, a C-A mutation at the third nucleotide of an acceptor site consensus sequence, has been described previously only in one Egyptian, one Iranian, one Tunisian, and one Black American patient. Nine other alleles each accounted for 1-3% of beta-thalassemia genes. Among these was one codon 27 allele (Hb Knossos), two frameshift 106/107 alleles previously seen only in a Black American, and a rarely observed mutation in the distal promoter region of the beta-globin gene, -87 (C-A). Our results suggest that from a molecular genetic standpoint a beta-thalassemia prevention program based on carrier screening and prenatal diagnosis can be implemented in Egypt. In couples at risk for beta-thalassemia, the causative mutation should be identifiable in both members in 92% and in one member in the remaining 8%. PMID- 8477264 TI - Deletions with inversions: report of a mutation and review of the literature. AB - Herein we report a 10.9 kb deletion and a 95 bp inversion in a patient with severe hemophilia B (factor IXHB209). With the addition of factor IXHB209, three of six characterized deletions in the factor IX gene are now known to include inversions. A high frequency of combined deletions and inversions has not previously been described in a human gene. PMID- 8477265 TI - Detection of point mutations in the p53 gene: comparison of single-strand conformation polymorphism, constant denaturant gel electrophoresis, and hydroxylamine and osmium tetroxide techniques. AB - A comparison was made between the 3 most commonly used techniques for the detection of point mutations: single-strand conformation polymorphism (SSCP), constant denaturant gel electrophoresis (CDGE), and hydroxylamine and osmium tetroxide used in amplification mismatch cleavage analysis (HOT). Using human DNA samples containing known mutations in the p53 gene, SSCP detected 90% of mutations (18/20), CDGE detected 88% (15/17) pre-decoding of the samples but 100% when the mutations were known and the CDGE conditions optimized, and the HOT technique was 100% accurate, although 1 mutation was missed through careless examination of the gel. The positive and negative aspects of each of the techniques are considered and suggestions are made regarding the particular situations in which each of them is most useful. PMID- 8477266 TI - A rapid and reliable PCR method for genotyping the ABO blood group. AB - The ABO blood group has been used extensively as a marker in population studies, epidemiology, and forensic work. However, until the cloning of the gene, it was not possible to determine the genotype of group A and B individuals without recourse to family studies. We have developed a method to determine the ABO genotype directly from human DNA using multiplex PCR and restriction enzyme analysis. Two PCR fragments spanning positions 258 and 700 of the cDNA sequence are amplified. The site at position 258 allows us to differentiate the O allele from the A and B alleles. The site at position 700 allows us to distinguish the B allele from the A and O alleles. Analysis at the two sites thus allows us to distinguish the three alleles. The multiplex PCR product is digested separately with four enzymes, two for each of the sites. The pair of enzymes for each site cut in a reciprocal fashion. Whereas one enzyme for each site is theoretically sufficient for genotyping, the use of complementary pairs of enzymes prevents the assignment of a false genotype as a result of false negative or partial digestion. This method is fast and reliable, does not rely on probing of blots, and should be widely applicable. PMID- 8477267 TI - A deletion/insertion mutation in the IDUA gene in a Libyan Jewish patient with Hurler syndrome (mucopolysaccharidosis IH). PMID- 8477268 TI - G6PD "campinas:" a deficient enzyme with a mutation at the far 3' end of the gene. PMID- 8477269 TI - Sexual abuse and eating disorders: a review. AB - Studies investigating a possible relationship between sexual abuse and eating disorders have reported highly discrepant results. Some variability can be accounted for by methodological issues including diagnostic criteria, study design, and assessment techniques. The heterogeneity of an eating disordered population, especially regarding the comorbidity of eating pathology and personality disorder, is also a factor. Overall results suggest that around 30% of eating disordered patients have been sexually abused in childhood, a figure that is relatively comparable to rates found in normal populations. For some patients there may be a direct link between sexual trauma and eating pathology, but in general sexual abuse is best considered a risk factor in a biopsychosocial etiological model of eating disorders. Complex associations between trauma, self regulatory deficits, and psychopathology require further research. PMID- 8477270 TI - Demographic and clinical correlates of selective information processing in patients with bulimia nervosa. AB - Demographic and clinical correlates of interference with color-naming words related to eating, weight, and shape were investigated in 75 patients with bulimia nervosa. Interference with color-naming was related to two measures, overall level of psychiatric symptoms and frequency of purging. Multiple regression analysis showed that frequency of purging, and not level of general psychiatric symptoms, was the best predictor of interference. Thus, as would be predicted by cognitive theories, interference appears to be most closely related to features specific to bulimia nervosa rather than to measures of general psychopathology. PMID- 8477271 TI - Adaptation to severe chronic hypokalemia in anorexia nervosa: a plea for conservative management. AB - Severe hypokalemia may constitute a life-threatening medical emergency. In the group of purging eating disorder patients, potassium blood levels tend to be chronically low while physical signs and symptoms may be absent. Nevertheless, these patients are frequently subjected to vigorous supportive treatment and often an aggressive diagnostic workup. We present a chronic purging anorexia nervosa patient in whom potassium blood levels reach a low of 1.6 mmol/L in the absence of physical symptoms. Purging eating disorder patients adapt to chronic hypokalemia. We believe the clinical/medical approach to this electrolyte disturbance in chronic eating disorder patients should be different from the approach to patients suffering from acute hypokalemia. PMID- 8477273 TI - Recent research bibliography. PMID- 8477272 TI - Eating pathology in bulimia nervosa. AB - Degree of eating pathology in bulimia nervosa was assessed using the Eating Behavior Rating Scale (EBRS) across three videotaped eating sessions. Twelve bulimic and 12 non-eating disordered subjects participated in this study. All subjects were filmed during a baseline meal (ad libitum), a high-calorie meal, and a low-calorie meal (both fixed amounts). Mean EBRS scores were significantly higher for bulimics (12.6 +/- 1.7) than for controls (3.9 +/- 0.9), suggesting a higher degree of eating pathology in these patients. Affect during eating was significantly more negative in the bulimic patients. EBRS and affect scores were significantly correlated [r (11) = .813, p < .01]. Bulimics had a slower rate of eating than controls and took significantly longer to initiate eating. Scores of pathological eating correlated with scores on the Eating Attitudes Test and the Bulimic Investigatory Test-Edinburgh, indicating a relationship between objective measures of pathological eating and self-report measures of eating disorder symptoms. PMID- 8477274 TI - Assessment of binge eating in obese patients. AB - Obese patients entering a weight control program were classified as binge eaters if they reported uncontrolled consumption of what others would regard as an unusually large amount of food at least once a week for the previous month. Binge eaters differed significantly from nonbingers across a broad range of eating and weight-related characteristics assessed using a self-report version of the Eating Disorder Examination. Attitudinal differences were marked. The results provided no support for the view that obese binge eaters have a pattern of general "addictiveness" to psychoactive substances or other activities. PMID- 8477275 TI - Patients with bulimia nervosa who fail to engage in cognitive behavior therapy. AB - Although cognitive behavioral treatment is the treatment of choice in bulimia nervosa, patients' response is variable. A minority of patients do not respond at all and some never engage in treatment. This paper concerns the latter group. A case series of six such patients with whom treatment could not be initiated is compared with a group who received a full course of treatment. The group with whom treatment could not begin were found to have a longer history of disorder, to report excessive laxative abuse, to have more severe depressed mood and a greater dissatisfaction with their body weight. In addition, they were more likely to have abused psychoactive substances, engaged in episodes of self-harm, and have a lower self-esteem. They were also more likely to be diagnosed as having borderline personality disorder. Patients presenting with the wide range of difficulties characteristic of this group require a more intensive form of treatment than standard outpatient cognitive behavior therapy. PMID- 8477276 TI - Pregnancy and eating disorders: a review and clinical implications. AB - Pregnancy and eating disorders is a subject that has received relatively little attention in the literature. Yet, several serious complications have been found in both the mother and the fetus when a woman with an eating disorder becomes pregnant. In this paper the literature is reviewed for both anorexia nervosa and bulimia nervosa and suggestions for future research are offered. Clinical implications for the treatment of the pregnant eating disordered patient are discussed. PMID- 8477277 TI - Comorbidity of bulimia and substance abuse: perceptions of family of origin. AB - Clinical characteristics and perceptions of family of origin were examined in 16 bulimic women with comorbid alcohol abuse or dependence, 17 women with bulimia alone, and 30 normal controls. Family Environment Scale self-report and Family Environment Q-sort analysis of taped semi-structured interviews about family environment revealed that while there were no differences across groups in global family environment items, differences existed in specific parental characteristics. Fathers of bulimic women (with or without alcohol abuse or dependence) were perceived as being significantly more seductive than fathers of normal controls. Bulimic women (with or without alcohol abuse or dependence) tended to view their mothers as more neurotic and to have experienced less enjoyment in their maternal role. Mothers of bulimic women with alcohol abuse tended to place the greatest emphasis on weight, exercise, and appearance. PMID- 8477278 TI - An investigation of the influence of dieting and self-esteem on dietary disinhibition. AB - Recent research on the eating behavior of restrained eaters following a dietary preload indicates that both dieting and self-esteem may influence consumption. While Polivy, Heatherton, and Herman (Journal of Abnormal Psychology, 97, 354 356, 1988) found a forced preload to lead to increased consumption by low self esteem restrained eaters, Lowe, Whitlow, and Bellwoar (International Journal of Eating Disorders, 10, 461-471, 1991) found restrained dieters to decrease their consumption following a dietary preload. The current study was designed to investigate the influences of self-esteem and dieting on the eating behavior of restrained eaters while in a negative mood state. Subjects were 80 normal weight undergraduate women in a 2 x 2 x 2 design (Restrained/Unrestrained by Success/Failure by Low Self-Esteem/High Self-Esteem). Current dieting, though not self-esteem, was found to influence consumption. Restrained dieters consumed significantly less in a negative mood state than when in a positive mood state, while nondieters, irrespective of restraint status, consumed comparable amounts in both mood states. PMID- 8477279 TI - The measurement of restraint: confounding success and failure? AB - The present study examined the concept of restrained eating as measured by the Restraint Scale and the restrained eating section of the Dutch Eating Behaviour Questionnaire. The results showed that when answering questionnaires, subjects do not differentiate between items relating to attempts at dieting and actual restrictive behavior and that restrained eating can be conceptualized in terms of both successful and failed restraint. In addition, the results suggest that subjects who report high scores on both these measures of restraint represent a population of dieters prone to overeating behavior. The results are discussed in terms of the population selected by measures of restrained eating and in relation to the definition of restraint. PMID- 8477280 TI - Fluctuations in body satisfaction across situations. AB - Although the variable nature of body image was underscored by Schilder (The image and appearance of the human body. New York: International Universities Press, 1950), few investigators have addressed the stability of body image or its sensitivity to variation in environmental or situational conditions. Most researchers have assumed that body image is a stable characteristic. The present study was designed to investigate the situational specificity of body satisfaction, one facet of body image. One hundred forty-four undergraduate women indicated their degree of body satisfaction in general and in the following four situations: (a) walking by a group of attractive men and women at the beach in a bathing suit, (b) having a conversation with a close female friend over lunch, (c) getting dressed to go to school in privacy, and (d) trying on bathing suits in the dressing room of a department store. Body satisfaction varied significantly across the four situations for all body parts except the face, hair, and hands. Additionally, body satisfaction scores were found to reflect how subjects felt about their bodies when they were being especially self-critical, rather than how they felt in "everyday" situations. PMID- 8477281 TI - Generality in the errors of estimation of body image. AB - An aspect of the considerable research on the association between eating disorders and discrepancies in body image estimation is the extent, if at all, that such discrepancies could be due to a more general tendency to show a positive or negative bias in estimation of the size of objects. One hundred female subjects, without known eating disorder, estimated the width of their own bodies (head, shoulders, waist, and hips), of another person's body (waist and hips), of four commercial packages, and of a cylinder. Errors in estimation, computed as algebraic differences from the true value, were computed, and all error means were found to be positive. Correlations between the error scores were all positive. Factor analysis of the correlations between the 11 error scores indicated a substantial general factor plus a bipolar factor, or alternatively two positively correlated factors referring to human body or physical measures. Results were interpreted as supporting the notion of a broad general tendency to enhance or diminish estimations of the width of familiar objects including estimations of the width of own body parts. The relevance of this finding to eating disorders was discussed. PMID- 8477282 TI - Toward an empirically derived typology of obese persons: derivation in a nonclinical sample. AB - The purpose of this research was to empirically derive a typology of obese persons and validate a typology derived in earlier research (Allison & Heshka [1991] International Journal of Obesity). Biological, behavioral, and psychological variables were assessed through survey among 719 (641 females, 78 males) obese members of The National Association to Advance Fat Acceptance (NAAFA). All variables were subjected to principal components analyses which extracted 12 biological and 12 psychological components. A two-cluster solution from a k-means clustering on biological components was replicated via Ward's method. Agreement between the solutions was significant (Phi = .33, Kappa = .19, p < .05). The solution was validated through entering psychological component scores into discriminant analysis. One significant function (p < .001) substantially separated the clusters. A component measuring early onset/familial history powerfully discriminated between the clusters. Early onset obese were more obese, more active, and restricted caloric intake to a greater degree. Late onset obese were more likely to be "settled down," engage in substance abuse, eat at night, and have diabetes (p < .05). Results were substantially consistent with those of prior research. PMID- 8477283 TI - Binge eating disorder: its further validation in a multisite study. AB - Binge eating disorder (BED) is a new eating disorder that describes the eating disturbance of a large number of individuals who suffer from recurrent binge eating but who do not regularly engage in the compensatory behaviors to avoid weight gain seen in bulimia nervosa. This multisite study of BED involved 1,785 subjects drawn from 18 weight control programs, 942 subjects from five nonpatient community samples, and 75 patients with bulimia nervosa. Approximately 29% of subjects in weight control programs met the criteria for BED. In the nonpatient community samples BED was more common than purging bulimia nervosa. The validity of BED was supported by its strong association with (1) impairment in work and social functioning, (2) overconcern with body/shape and weight, (3) general psychopathology, (4) significant amount of time in adult life on diets, (5) a history of depression, alcohol/drug abuse, and treatment for emotional problems. PMID- 8477284 TI - The classification of recurrent overeating: the "binge eating disorder" proposal. AB - It has been suggested that a new diagnostic category be added to the section on eating disorders in DSM-IV. This new diagnosis has been termed binge eating disorder. In this article we argue that for two main reasons it would be a mistake to include binge eating disorder in DSM-IV: first, too little is known about binge eating and other related forms of recurrent overeating to justify its inclusion in DSM-IV; and second, its inclusion would be a source of diagnostic confusion. We argue that it is premature to crystallize this specific subgroup from amongst those who recurrently overeat and that to do so would impede the acquisition of knowledge rather than enhance it. We advocate a research strategy that involves studying broad samples of those with recurrent overeating rather than narrow ones. PMID- 8477285 TI - Binge eating disorder should be included in DSM-IV: a reply to Fairburn et al.'s "the classification of recurrent overeating: the binge eating disorder proposal". AB - Extensive recent research supports a proposal that a new eating disorder, binge eating disorder (BED), be included in DSM-IV. BED criteria define a relatively pure group of individuals who are distressed by recurrent binge eating who do not exhibit the compensatory features of bulimia nervosa. This large number of patients currently can only be diagnosed as eating disorder not otherwise specified (EDNOS). Recognizing this new disorder will help stimulate research and clinical programs for these patients. Fairburn et al.'s critique of BED fails to acknowledge the large body of knowledge that indicates that BED represents a distinct and definable subgroup of eating disordered patients and that the diagnosis provides useful information about psychopathology, prognosis, and outcome (Fairburn, Welch, & Hay [in press]. The classification of recurrent overeating: The "binge eating disorder" proposal. International Journal of Eating Disorders.) Against any reasonable standard for adding a new diagnosis to DSM-IV, BED meets the test. PMID- 8477286 TI - Anorexia nervosa "restricters" who purge: implications for subtyping anorexia nervosa. AB - It has not been clear from earlier studies whether it is binge eating per se or the compensatory behaviors frequently associated with binge eating (i.e., self induced vomiting and/or laxative abuse) that provide the most relevant marker for subclassifying anorexia nervosa. The current study addressed this question by comparing the clinical and psychological features of three groups of anorexia nervosa patients: "pure restricting" patients who do not binge (by definition) and who also do not purge (AN-R, N = 116); "restricting-purging" patients who engage in purging behavior (AN-RP, N = 74); and anorexia nervosa "bulimics" who binge eat as defined in earlier studies (AN-B, N = 190). While all three groups displayed similar levels of psychological disturbance on many variables, the overall pattern of findings indicates that the AN-RP group displays significantly more psychopathology than the AN-R group and their profile of disturbance is very similar to that observed with the AN-B group. Thus, anorexia nervosa patients who purge, regardless of whether or not they report objective binge episodes, may be meaningfully distinguished from nonpurging patients. These results, combined with the medical risks associated with purging behaviors and the formidable problems associated with the definition of binge eating, support a sub-typing system for anorexia nervosa based on the presence or absence of purging rather than binge eating. PMID- 8477287 TI - Dissociative experiences and trauma in eating disorders. AB - This study explores the relationship between traumatic experiences and dissociative phenomena in a large group of eating disorder patients (N = 98). Traumatic experiences were assessed by means of a self-report questionnaire and a clinical interview; dissociative experiences were assessed with the newly developed self-reporting Dissociation Questionnaire (DIS-Q). About 25% of the patients reported to have experienced traumatic events in their personal life and this subgroup had significantly higher scores on the DIS-Q, compared with normal control subjects. About 12% of our patient sample mentioned dissociative experiences to a degree as high as in a group of patients with dissociative disorders. Amnesia turned out to be the most specific characteristic in trauma induced dissociation. These data suggest that trauma-induced dissociative experiences may play an important role in the development of a subgroup of patients with an eating disorder. PMID- 8477288 TI - The use of electroconvulsive therapy in patients with intractable anorexia nervosa. AB - The history of the treatment of anorexia nervosa includes the majority of psychological and somatic therapies devised by psychiatrists, psychologists, and general physicians. We review the history of one of these treatments, electrical convulsive therapy (ECT), and discuss three patients treated with ECT for primary anorexia nervosa. Two had a positive response to this treatment, one did not. She later responded favorably to a course of treatment with fluoxetine. PMID- 8477289 TI - Food intolerance in patients with chronic fatigue. AB - Intolerance to various foods is reported often by patients seeking evaluation for chronic fatigue, a common symptom in primary care practice. To assess the prevalence and significance of this phenomenon we studied 200 consecutive patients with chronic fatigue who were given a comprehensive medical and psychiatric evaluation. Intolerance to foods from at least three different groups was reported by 27 patients (13.5%). We compared these patients with 27 age- and gender-matched patients from the same cohort of fatigued patients. Physical examination and laboratory testing showed few abnormalities in either group. The two groups were similar with respect to the duration and severity of fatigue, lifetime depressive symptoms, and prevalence of current depressive disorders (67% vs. 63%) and anxiety disorders (11% vs. 15%). Patients with multiple food intolerance had more lifetime functional somatic symptoms (p < .05) and a significantly higher (33% vs. 7%) prevalence of somatization disorder (p < .025). These data suggest that intolerance to multiple foods is probably not a cause or the effect of chronic fatigue, but rather one of the manifestations of the somatization trait expressed in these patients. PMID- 8477290 TI - The effects on eating of dietary restraint, anxiety, and hunger. AB - In this study a comparison was made between the amounts eaten by restrained and unrestrained eaters following an anxiety-induction procedure. Subjects' level of perceived hunger was assessed and the interactive effects on eating of anxiety and perceived hunger were examined. Results revealed a significant three-way interaction. Unrestrained subjects did not alter their eating in response to either anxiety or hunger. When relaxed, restrained subjects ate more when hungry than when not hungry. However, in restrained subjects, anxiety appeared to counteract the disinhibiting effect of hunger, so that anxious hungry subjects ate less than relaxed hungry subjects and the same amount as relaxed subjects who were not hungry. PMID- 8477291 TI - The self-image of adolescent patients with eating disorders. AB - Forty German adolescent anorectic patients were assessed with regard to self image components as measured by the Offer Self-Image Questionnaire (OSIQ). The profile of this group deviated negatively from the German standardization group of healthy subjects on measures of impulse control, emotional tone, body image, social relationships, sexual attitudes, and psychopathology. In addition, the OSIQ profile of this German sample was remarkably similar to the profiles of samples reported in two American studies. Finally, it was found that inpatient treatment served to improve the psychological condition of the patients with regard to certain but not all self-image components. Despite a trend of improvement, some of the scores did not fully normalize in this sample. PMID- 8477292 TI - Dietary zinc intake of vegetarian and nonvegetarian patients with anorexia nervosa. AB - Anorexia nervosa (AN) and zinc deficiency, found most frequently in young females, have a number of symptoms in common. These include weight loss, alterations in taste and appetite, depression, and amenorrhea. Approximately half of anorexia nervosa patients (ANs) are vegetarian (VANs), a practice that may increase their risk for zinc deficiency. This study compared the dietary intake of zinc and related nutrients in 9 outpatient VANs with that of 11 outpatient nonvegetarian patients with anorexia nervosa (NVANs). VANs reported significantly lower (p < .05) dietary intakes of zinc, fat, and protein, and a significantly higher (p < .05) intake of calories from carbohydrates than NVANs. There were no significant differences between the groups in dietary intake of calories, calcium, copper, iron, or magnesium. These findings indicate that zinc intake should be routinely assessed in VANs and that zinc supplementation of their diets may be indicated. PMID- 8477293 TI - Multiple personality in eating disorder patients. AB - Although the overlap between childhood sexual and physical abuse and eating disorders is well known, little work has been done on the sequelae of childhood trauma in eating disorder patients. Dissociative phenomena are common in adult survivors of childhood abuse, with multiple personality disorder (MPD) being the most extreme form of dissociative disorder. We describe two women who presented for inpatient treatment of eating disorders who were subsequently found to have MPD. Because the eating pathology in these patients contained atypical features related to the MPD process, uncovering MPD was critical in the treatment of their eating behavior. MPD should be considered in any atypical or treatment-resistant eating disorder patient. PMID- 8477294 TI - Case report of anorexia nervosa associated with Wilson's disease. AB - Wilson's disease is a recessively inherited disorder of copper metabolism with prominent hepatic, hematopoietic, central nervous system (CNS), and ocular involvement. Psychiatric manifestations are notoriously variable. The following case history of a patient with both anorexia nervosa and Wilson's disease is presented and discussed in the context of organic CNS lesions associated with anorexia nervosa-like syndromes. PMID- 8477295 TI - Eating disorder in a 6-year-old Asian girl with ethyl malonic adipic aciduria. AB - Accurate data are not available for the prevalence of eating disorders amongst the Asian population in Britain. Only a handful of cases have been reported in the literature [Bhadrinath (1990). British Journal of Psychiatry, 156, 565-568.] suggested that it is an uncommon phenomenon despite Dolan's recent finding [Dolan, Lacey, & Evans (1990). British Journal of Psychiatry, 157, 523-528.] that there were elevated Eating Attitudes Test (EAT) scores in a sample of young Asian adults compared with Caucasians. We report a case of an Asian girl with a rare inborn error of metabolism and an eating disorder. PMID- 8477296 TI - The impact of sexual and physical abuse on eating disordered and psychiatric symptoms: a comparison of eating disordered and psychiatric inpatients. AB - The authors compared rates of physical and sexual abuse in women with eating disorders (N = 102) and general psychiatric disorders (N = 49). Relationships between sexual abuse and severity of eating disordered and psychiatric symptoms were also examined. While high rates of sexual abuse were found in the eating disordered sample, these rates were not significantly higher than those found in the general psychiatric population. No relationship between a history of sexual abuse and severity of eating disordered symptoms was found. However, within the eating disordered group, sexually abuse subjects reported more severe psychiatric disturbances of an obsessive and phobic nature than nonabused subjects. These findings suggest that while sexually abusive experiences may be related to increased psychological distress, they do not serve to increase eating disordered symptomatology. PMID- 8477297 TI - Association of sexual abuse and borderline personality disorder in eating disordered women. AB - It has been shown that sexual abuse is associated with the eating disorders, particularly those with a bulimic component. Existing research suggests that borderline personality disorder (or the cluster of behaviors behind this diagnosis) may be a mediating factor in that link. However, there is no evidence of specific patterns of association between the three phenomena. The present report studies these links in a case series of 115 eating-disordered women. It is shown that the links between and reported sexual abuse and borderline personality disorder vary according to the nature of the eating disorder. In particular, they were associated in anorexia of the bulimic subtype, but not in bulimia nervosa or in restrictive anorexia. The possible therapeutic implications of these findings are discussed. PMID- 8477298 TI - Bulimia nervosa: a population-based study of purgers versus nonpurgers. AB - There has been recent interest in the possibility of dividing bulimia nervosa into two subtypes based on the method of weight prevention utilized by the individual. In an attempt to see if such a division is justified, this study compared 54 purging bulimics with 69 nonpurging bulimics ascertained from a population-based register of Virginia female twins. A bulimic was defined as a "purger" if she engaged in vomiting or laxative abuse. These two groups were examined on a variety of demographic, weight, and personality measures after controlling for the presence of obesity. No significant differences were found between the two groups on any of the variables examined. PMID- 8477299 TI - Self-treatment of bulimia nervosa: a pilot study. AB - Twenty-eight patients with ICD-10 bulimia nervosa or atypical bulimia nervosa were given a cognitive-behavioral treatment handbook and were reassessed 4-6 weeks later. On a clinician-rated global improvement scale 12 patients had much improved and 8 patients had somewhat improved. Fifteen patients were abstinent of vomiting or laxatives at reassessment as opposed to five patients before treatment. Of the 21 patients who were bringing before treatment, 7 had a 75-100% reduction of binges and 5 had a 50-75% reduction of binges. Patients' nutritional knowledge increased significantly. A patient-administered hand-book may be a useful first intervention in the treatment of patients with bulimia nervosa. PMID- 8477300 TI - Expressed emotion in the investigation of eating disorders: a review. AB - Expressed Emotion (EE) is a measure of family interaction that has been shown to be useful for the investigation of many psychiatric disorders. This paper describes why it is appropriate to use it for the investigation of eating disorders. There is discussion of the findings that the levels tend to vary between the different eating disorders. The relationship between EE and treatment response is discussed. Suggestions are made for further research. PMID- 8477301 TI - Emotion and eating in obesity? A critical analysis. AB - Psychosomatic theories hold that the obese abnormally increase eating in response to emotional distress. Empirical support for this assertion has come mainly from self-report studies. A review of the literature for methodological rigor reveals that many studies previously considered supportive are substantially flawed with regard to control groups, failure to control Type-I error rate, and the possibility of confounding of social desirability and other response sets with self-reports of emotional eating. Five alternative conceptualization of the obesity-emotional eating association are presented along with suggested research which would elucidate the nature of this frequently reported connection. PMID- 8477302 TI - A problematic counter-regulation experiment: implications for the link between dietary restraint and overeating. AB - The current study failed to find any evidence of laboratory counter-regulation amongst restrained eaters given a preload, regardless of the measures of dietary restraint used to classify subjects, including dieting status on the day of the study. Furthermore, there was no evidence to suggest that high restrainers characteristically overeat or experience a sense of loss of control over eating in naturalistic settings. These findings indicate that the link between dietary restraint and overeating or bulimic episodes is, at most, a weak one. Future investigations must incorporate more detailed and sensitive measures of both restraint and overeating if analogue studies are to be useful for understanding the process involved in clinically significant episodes of overeating or binge eating. PMID- 8477303 TI - Effects of high calorie preloads on selective processing of food and body shape stimuli among dieters and nondieters. AB - Preloaded and nonpreloaded dieters (restrained eaters) and nondieters (unrestrained eaters) completed a modified version of the Stroop task to measure selective biases in cognitive processing. In two separate studies, a milkshake preload led to increased cognitive interference for body shape words, especially for restrained eaters. There were no differences between restrained and unrestrained eaters in Stroop interference for either common or forbidden food words, whether subjects were preloaded or not. Taken together, these results indicate that chronic dieting is associated with selective processing of body shape words. PMID- 8477304 TI - Body Shape Questionnaire: derivation of shortened "alternate forms". AB - The 34-item Body Shape Questionnaire (BSQ) has demonstrated sound psychometric properties in all samples reported to date (including this study). However, the unidimensional nature of the 34 items suggests that the BSQ may be unnecessarily long for use in studies when body disparagement is not the main focus of investigation. This study of 342 adult women presents two 16-item "alternate forms" of the BSQ which showed equivalent means and excellent internal consistency in both derivation and replication samples. Two 8-item scales were also derived. The 34-, 16-, and 8-item versions showed equivalent convergent and discriminant validation against the Eating Attitudes Test (EAT)-26 and other parameters. We suggest that use of these 16-item versions may be more efficient than the original BSQ where body disparagement is not the sole focus of a study, or where a repeated measures design is employed. Furthermore, the 8-item versions are sufficiently robust to be used as "alternate forms" where speed of completion and economy are of the essence. PMID- 8477305 TI - Body image changes during early adulthood. AB - Results from recent studies on body image have revealed differences between college-age individuals and older samples. In this study, adults 17 to 40 years old were evaluated for their body dissatisfaction on the Figure Rating Scale. Females had higher levels of body dissatisfaction than males and these differences did not diminish with age. However, consistent with physical changes in adulthood, current and ideal ratings became more discrepant with age. Interestingly, for women, affective and cognitive dimensions of body dissatisfaction became more consistent. Research on early adulthood personality development is used to help explain these results. PMID- 8477307 TI - Proceedings of the British Pharmacological Society Meeting. 5-7 January 1993. Abstracts. PMID- 8477306 TI - Dreams of death: Von Weizsacker's Dreams in so-called endogenic anorexia: a research note. AB - Viktor Von Weizsacker's paper "Dreams in so-called endogenic Magersucht (anorexia," first published in the Deutsche Medizinische Wochenschrift in 1937 (translation in M. Kaufman & M. Heiman [1964]. Evolution of psychosomatic concepts: Anorexia nervosa: A paradigm (pp. 181-197), New York: International Universities Press, has been described as a noteworthy and historically important contribution to the recognition of anorexia nervosa as a psychosomatic illness. Von Weizsacker analyzed the dreams of patients he was treating for "endogenous anorexia" (magersucht). He claimed that in the bulimic phase his patients experienced nightmares dealing with themes of death, but that in the anorectic phases of restricted eating more pleasant dreams dealt with themes of blissful contentment. The authors draw current attention to his work as another early example of the treatment of the theme of death and death symbolism in the literature on eating disorders, and suggest some reappraisal of von Weizsacker's interpretations of his own material. PMID- 8477308 TI - Effectiveness of haematuria clinics. PMID- 8477309 TI - Spontaneous rupture of renal tumours presenting as surgical emergency. AB - A study of renal tumours filed in the pathology department of a regional hospital in Hong Kong during 1971-1990 showed 6 cases of surgical emergency due to spontaneous rupture of the kidney by tumour. All occurred as a complication of renal angiomyolipoma, a rare tumour or hamartoma. A literature review showed that the renal tumour most frequently reported to cause spontaneous rupture was renal carcinoma. Chinese patients appear to have more renal ruptures due to angiomyolipoma than to renal carcinoma. It is proposed that intra-operative frozen section diagnosis should be sought, when this can be safely performed, in cases of rupture of the kidney by tumour. Surgery aiming at conserving functional renal parenchyma is appropriate for benign lesions such as angiomyolipoma. PMID- 8477310 TI - Aspects of hypertension in renal allograft recipients. A study of 1000 live renal transplants. AB - A retrospective study of 1000 live renal transplants was performed in order to assess the factors associated with hypertension in renal transplant recipients. The prevalence of hypertension prior to transplantation was 48%. The need for antihypertensive drugs decreased in 43%, increased in 31% and remained the same in 26%. The presence of hypertension before transplantation, rejection episodes, transplant renal artery stenosis and native kidney disease were the main factors associated with post-transplant hypertension. An algorithm for the management of post-transplant hypertension is suggested. PMID- 8477311 TI - Audit of catheter management provided by District Nurses and Continence Advisors. AB - District Nurses and Continence Advisors were surveyed by post to audit their management of long-term indwelling catheters. They were asked to outline, anonymously, their management strategies in response to common specified catheter related problems. The responses to each question were graded for the appropriateness of strategy from A (best) to E (worst) by previously formulated criteria. Completed questionnaires were returned from all 10 Welsh Continence Advisors and 73 of 139 (53%) District Nurses in South Glamorgan regularly involved in catheter care. A greater proportion of Continence Advisors' than District Nurses' responses were graded A or B in all problem areas specified. In patients with marked bacteriuria, 60% of Continence Advisors but only 11% of District Nurses would assess whether the patient was ill; 53% of District Nurses would treat with antibiotics without such assessment. Whereas most nurses investigating suprapubic pain would consider catheter blockage, only one-third would consider further history taking or examination, and only 1 District Nurse considered constipation or detrusor spasm. Although two-thirds of nurses sometimes used bladder washouts, few considered them effective and most were aware of the potential risks. Thus wide variations were found in the community nursing management of indwelling catheters and care may frequently be suboptimal. Appropriate management guidelines should be developed and disseminated. PMID- 8477312 TI - Is impaired perception of bladder filling during cystometry a sign of neuropathy? AB - The sensation of bladder filling during cystometry was evaluated in 627 consecutive patients. The groups of patients with various patterns of impaired sensation included significantly more patients with confirmed neuropathy than did the group whose perception of bladder filling was normal. When sensation was absent, or only 1 of 3 types was reported by patients without known neuropathy, further investigation revealed abnormal afferent innervation of the lower urinary tract in 35%. These data suggest the need for further neurological evaluation in such patients. PMID- 8477313 TI - The incidence of bladder cancer in the black foot disease endemic area in Taiwan. AB - A high incidence of bladder cancer (23.53/100,000 population per annum from 1981 1985) was found in an endemic area of peripheral vascular disease known as black foot disease (BFD) on the southwest coast of Taiwan. The average incidence of bladder cancer in the whole of the Taiwan area was 2.29/100,000 during the same period. The incidence of female bladder cancer (21.10/100,000) in this area was also high. The ratio of male to female bladder cancer in the BFD endemic area and the neighbouring area was 1.24 and 1.09, lower than that in the whole Taiwan area (2.75) and elsewhere around the world. The high content of arsenic and the high concentration of a "fluorescent substance" in artesian well water in this area are the only 2 related factors identified so far. Determination of the actual carcinogen requires further investigation. PMID- 8477314 TI - Bromodeoxyuridine labelling of transitional cell carcinoma of the bladder--an index of recurrence? AB - Nineteen patients with newly diagnosed transitional cell carcinoma of the bladder consented to receive an intravenous bolus of bromodeoxyuridine (BrdUrd) 3 to 6 h prior to transurethral resection of bladder tumour. Routine paraffin embedded sections were stained with anti-BrdUrd monoclonal antibody in order to determine the S phase fraction of the bladder tumours and to correlate this with tumour grade, category and the development of recurrence during follow-up. BrdUrd labelling of nuclei was reliably detected in 100% of the tumours. The mean labelling index of Ta tumours (n = 8) was 3.14%; in T1 tumours (n = 7) it was 8.6% and in T2-3 tumours (n = 4) it was 16.4%. A similar correlation was found in association with tumour grade. The patients were followed up for a mean of 23 months (range 18-30). Seven of the 15 superficial tumours recurred during the period of follow-up. These tumours had a mean labelling index (at diagnosis) of 8.4%, whereas the tumours that did not recur had a mean labelling index of 3.4%. The in vivo determination of BrdUrd uptake in transitional cell carcinoma of the bladder may be useful in predicting which superficial tumours are likely to recur following resection and so rationalise both the time to follow-up and intravesical chemoprophylaxis. PMID- 8477315 TI - Multivariate analysis of progression in superficial bladder cancer. AB - A total of 217 patients with superficial bladder cancer (SBC) category Ta-T1 were retrospectively analysed for tumour progression and prognostic factors; 46% of patients presented with recurrences, 13% with increasing grades of anaplasia and 12% with progression in tumour category. The mean annual index of recurrences was 0.7 +/- 0.1; 4% of patients died from tumour progression and the overall 5-year survival rate was 88% +/- 5.3. Factors that influenced progression significantly were peritumoural dysplasia, inflammatory infiltrate, residual tumour following transurethral resections, increasing grade of anaplasia and index of recurrences > 0.7. Multivariate statistical analysis revealed that only tumour category and increasing grade of anaplasia had significant prognostic value. Increasing grade of anaplasia predicts the likelihood of tumour progression with a 91% global predictive capacity. Thirty percent of patients with tumour progression did not have an increasing grade of anaplasia. Among these 87% were Ta, 50% were GI and the mean index of recurrences was 0.9. All were conservatively treated and 87% are alive. Among the patients with an increasing grade of anaplasia and tumour progression the mean index of recurrences was 1.7; 67% developed muscle infiltrating cancer and 7% metastatic spread without local progression; 64% of these patients died from cancer. An increasing grade of anaplasia affects prognosis. It defines patients with a high risk of tumour progression and tumour related death, especially those with T1 bladder cancer. PMID- 8477316 TI - Randomised study of the effect of midnight versus 0600 removal of urinary catheters. AB - A randomised controlled trial was undertaken to determine the effects of midnight removal of urinary catheters on patients' voiding patterns and subsequent discharge from hospital. Patients whose urinary catheters were removed at midnight showed a greater volume of initial void than those whose catheters were removed at the usual time of 0600. Removal of urinary catheters routinely at midnight permits earlier assessment of patients' voiding, which may allow for earlier discharge from hospital. PMID- 8477317 TI - Hormonal treatment of obstructed kidneys in patients with prostatic cancer. AB - A review of 1288 patients with previously untreated prostatic cancer revealed 209 patients (16%) with ureteric obstruction; the obstruction was bilateral in 36%. The effect of hormonal treatment was assessed in 88 patients with 120 obstructed kidneys: 77 patients had androgen deprivation or hormonal medication alone and 11 patients needed percutaneous nephrostomy or ureteric catheters in addition. Drainage improved in 58% of the kidneys. The diverting catheter was withdrawn in 9 of the 11 patients after a median of 4 weeks. In all, 95% of patients were discharged. The patients with hormonal therapy alone survived for a median of 26 months (range 1-111), while the patients who also needed diversion survived for a median of 13 months (range 1-28). The median time spent at home was 24 months (0 102) and 10 months (0-23) respectively, presumably reflecting the worse general condition of the patients who required diversion. PMID- 8477318 TI - New, self-expanding, self-retaining temporary coil stent for recurrent urethral strictures near the external sphincter. AB - Strictures near the external sphincter are a cause for concern. They can be managed by manipulation (e.g. urethral dilatation) or by anastomotic urethroplasty. Permanently implanted metallic stents have recently been used to treat recurrent urethral strictures. This report presents the results of using a temporary metallic coil stent (UROCOIL-S) in 20 patients with recurrent bulbomembranous strictures. In 13 patients the stent was left in place for 10 months and was then removed by a simple manipulation. After a mean follow-up of 10 months (range 3-14), the stricture recurred in only 1 patient. The use of a temporary (but long-term) stent for the treatment of urethral stricture is a new approach and the results are encouraging. PMID- 8477319 TI - Results and complications of urethroplasty and its future. AB - A consecutive series of 200 patients undergoing urethroplasty has been reviewed to assess the results and complications of surgery and thereby assess the role of urethroplasty in the treatment of urethral strictures with particular reference to the current interest in intraluminal "stenting" of strictures. Anastomotic urethroplasty for post-traumatic strictures and "patch" urethroplasty for post infective strictures give satisfactory results which at present do not seem to be bettered by any other form of treatment. Urethroplasty for so-called "ischaemic" strictures gives less satisfactory results which could almost certainly be improved upon by intraluminal "stenting" or some other novel form of treatment. The incidence of impotence, temporary and permanent, after urethroplasty is probably greater than is generally realised and the aetiology of this complication warrants serious investigation as this is the single most important limiting factor in urethroplasty. PMID- 8477320 TI - Treatment of vesicoureteric reflux. Results of a prospective study. AB - Between 1982 and 1986, 96 children with non-obstructive vesicoureteric reflux were included in a prospective study. Three patients withdrew from the study and results are therefore presented on 93 children with 135 refluxing ureters who were followed up for at least 5 years. Initially, all children with reflux grade III or less received antibiotic treatment only. Those with reflux grade IV were randomised to antibiotic treatment alone versus surgery plus antibiotic treatment; the primary treatment of reflux grade V was reimplantation. In 85 ureters treated by antibiotics only, reflux disappeared in 64 cases and was reduced in 12. In 50 ureters treated by reimplantation, reflux was cured in 46 cases and no severe ureteric obstruction was seen. Conservative management of reflux grade IV was less successful than surgery. The results of conservative, non-surgical treatment of reflux grades I-III were satisfactory, but for grades IV and V surgery should be the treatment of choice if detrusor instability has been excluded. PMID- 8477321 TI - Female genito-urethroplasty and submucosal periurethral collagen injection as adjunctive procedures for continence in the exstrophy-epispadias complex. Preliminary results. AB - Continence is the main goal in the treatment of patients with bladder exstrophy and prognosis is necessarily long-term. Over an 8-year period, 44 patients presented with bladder exstrophy and/or incontinent epispadias. Twenty-five bladder closures (7 secondary), 23 male urethroplasties, 19 bladder neck (BN) reconstructions and 6 bladder augmentations were performed in these patients. In 18 children 2 additional procedures were employed in the last 3 years: female genito-urethroplasty (15) and submucosal periurethral collagen injection (11). Eight children underwent both procedures. Genito-urethroplasty and collagen injection were performed before BN reconstruction in 6 and 5 cases respectively, in order to increase bladder outlet resistance. The submucosal injection was performed at 3, 9 and 12 o'clock in the BN or sphincteric urethra, using 0.75 to 2.5 ml of cross-linked bovine collagen. Continence in the children who underwent the complete staged reconstruction was good in 58%, fair in 32% and poor in 11%. Following female genito-urethroplasty and periurethral collagen injection, bladder capacities increased by 25%. These complementary procedures are effective in increasing outlet resistance and bladder capacity in patients with exstrophy and/or epispadias; they may improve continence and lessen the need for further bladder augmentation. PMID- 8477322 TI - Apparent bilateral duplication of the vas deferens. PMID- 8477323 TI - Stabbing, haematuria, dysfunctional platelets and meningism: delayed recognition of Munchausen's syndrome. PMID- 8477324 TI - Peri-stomal varices: an unusual cause of bleeding from an ileal conduit. PMID- 8477325 TI - "Zig Zig Chug Chug"--a new urological symptom. PMID- 8477326 TI - Catheter psychosis. PMID- 8477327 TI - Congenital renal arteriovenous fistula. PMID- 8477328 TI - Recurrent right loin pain due to an accessory ureter. PMID- 8477329 TI - Suprapubic insertion of a Foley catheter: the forgotten technique. PMID- 8477330 TI - Cholecysto-nephroplasty. PMID- 8477331 TI - Unusual drainage of the bladder with a prostatic spiral in situ. PMID- 8477332 TI - Exclusive: revolutionary new design in catheter bag technology. PMID- 8477333 TI - Removal of retained Foley catheter. PMID- 8477334 TI - Re: Urological complications following live donor kidney transplantation: effect of urinary schistosomiasis. PMID- 8477335 TI - Re: Screening for bacteriuria in urological patients using reagent strips. PMID- 8477336 TI - Re: Renogastric fistula. PMID- 8477337 TI - The evolution of chemoreception in squamate reptiles: a phylogenetic approach. AB - Recent advances in the field of squamate reptile chemoreception have been paralleled by the growth and preeminence of cladistics in the field of systematics, but for the most part, workers in the former have failed to incorporate the conceptual and informational advances of the latter. In this paper, I attempt a preliminary rapprochement by combining the methods of phylogenetic systematics and current hypotheses of squamate relationships with an overview of squamate chemosensory biology. This purely phylogenetic approach leads to a number of falsifiable generalizations about the evolution of chemoreception in squamates: 1) Evolution of this system is conservative rather than plastic, reflecting to a large extent suprafamilial attributes rather than adaptation to local conditions; 2) Anguimorphs are highly chemosensory and teiids show convergence with this group; 3) Tongue-flicking, a bifurcated tongue tip, a vomeronasal (VNO) mushroom body, and a complete circular muscle system in the tongue are a correlated character complex associated with the attainment, in squamates, of a direct VNO-oral connection and the loss of a VNO-nasal connection; 4) There is little support for a visual-chemosensory dichotomy within Squamata; 5) Gekkotans are allied with Autarchoglossa, both phylogenetically and in terms of chemosensory biology; 6) Iguania are highly variable in chemosensory development; iguanids represent the primitive iguanian condition, while agamids and chamaeleonids have secondarily reduced or lost their chemosensory abilities; 7) Apparent contradictions in chemosensory behavior among iguanids probably represent intrafamilial divergence; 8) Ecological correlates within Iguanidae and other taxa might be spurious, resulting from historical factors unrelated to the adaptations in question; 9) The mechanical demands of lingual food prehension have constrained chemosensory evolution in Iguania; chemosensory evolution within Scleroglossa was permitted by the liberation of the tongue from this ancestral role. PMID- 8477338 TI - The comparative imperative: genetics and ontogeny of chemoreceptive prey responses in natricine snakes. AB - Reptiles offer a rich diversity for the study of chemoreception, and snakes are a particularly appropriate group for comparative, evolutionary, genetic, developmental, and mechanistic studies. A long-term program of research is described that attempts to integrate these approaches, focusing on the widespread North American genus Thamnophis (Natricinae). Prior to their first meal, neonatal snakes respond to aqueous surface substances from species-typical prey with increased tongue-flicking and open-mouth attacks; these responses are mediated by the vomeronasal organ. Such responses predict what prey snakes will eat and can also predict relative prey preference. Species, population, litter, and individual differences exists and are important at different levels of analysis. Chemoreceptive responses are heritable, although they may show different developmental trends. Some species respond to prey types they do not eat in nature. In the earthworm specialist, T. butleri, response to fish chemicals can be interpreted as a chemoreceptive response inertially inherited from ancestral species, decoupled from prey capture techniques, and in the process of being lost. Ontogeny and experience can modify behavior of the neonate in various ways. Feeding experience can alter response to some prey more than others, and ambient prey odor may shift prey preference. Psychophysical studies show that prey preference and threshold sensitivity to prey chemicals can be independent and differ between closely related species, indicating that neural tissue is devoted to recognition of specific types of prey. In site choice tests, garter snakes can also discriminate between feces derived from conspecific snakes fed similar or different diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477339 TI - Overview of the main and accessory olfactory bulb projections in reptiles. AB - The present account is a review of the main and accessory olfactory bulb projections in reptiles. From previous studies by means of the classical degeneration techniques and recent studies using the autoradiographic method or the Phaseolus vulgarus-leucoagglutinin (PHA-L) tracing technique, it has become evident that, in the brain of reptiles, the vomeronasal and main olfactory systems are segregated. Moreover, the PHA-L studies have demonstrated that the main olfactory bulbs project not only to the anterior olfactory nucleus, the olfactory tubercle, and the lateral cortex, but also to the rostral portions of the external and central amygdaloid nuclei. The latter studies also provided evidence that, apart from a massive projection to the nucleus sphericus, at least in some reptilian species, the accessory olfactory bulbs project to the caudal portion of the central amygdaloid nucleus and the bed nucleus of the stria terminalis. A comparison of the olfactory projections between the various reptilian species studied revealed a considerable variation in the course of the main olfactory bulb efferents that reach the contralateral hemisphere. PMID- 8477340 TI - Fiber connections of the amygdaloid formation of the lizard Podarcis hispanica. AB - The amygdaloid formation of the lizard Podarcis hispanica can be divided into three main groups of nuclei on the basis of their input from the main and accessory olfactory bulbs: the vomeronasal amygdala, the olfactory amygdala and the dorsal amygdaloid group, the latter group receiving afferents from neither the main (MOB) or the accessory olfactory bulb (AOB). The vomeronasal amygdala has a centrifugal projection to the AOB, an important commissural connection to the contralateral vomeronasal amygdala, a minor projection to nucleus accumbens, and a bilateral projection to the lateral cortex. The olfactory amygdala displays a bilateral afferents from the MOB, receives a contralateral afferent, and is reciprocally connected with the lateral cortex. Moreover, it receives an important input from the vomeronasal amygdala. The dorsal amygdaloid group receives projections from the other two amygdaloid groups, multimodal inputs from the anterior dorsal ventricular ridge and the dorsal cortex, and a putative cholinergic input from the basal telencephalon. Moreover, it is the site of origin of a prominent bilateral amygdalo-striatal projection that extends to the bed nucleus of the stria terminalis and the so-called amygdalo-striatal transition area, through which it may control both visceral and motor activities. The main extratelencephalic output of the amygdala courses through the stria terminalis and terminates in the ventromedial hypothalamic nucleus. The extratelencephalic afferents of the amygdala arise from several hypothalamic and anterior thalamic nuclei, from the mesencephalic and rhombencephalic aminergic cell groups, and from the rhombencephalic parabrachial nucleus. PMID- 8477341 TI - Chemical delivery to the vomeronasal organs and functional domain of squamate chemoreception. AB - While evidence exists that many squamate behaviors are released by chemical stimuli, the specific sensory system that detects such stimuli and mediates subsequent behavior has been determined infrequently. Techniques and experimental approaches that have been used to determine the roles that the main olfactory and vomeronasal systems play in mediation of specific behaviors are discussed. PMID- 8477342 TI - Central and endocrine aspects of tongue-flicking and exploratory behavior in Anolis carolinensis. AB - Tongue-flicking in reptiles is frequently seen to increase in novel habitats and is presumed to involve the acquisition of chemical information. Like most behavioral patterns, however, tongue-flicking has both multiple causes and multiple functions, only some of which involve chemosensation. This paper describes units of exploratory behavior, including use of the tongue, in a microsmatic lizard, the green anole, Anolis carolinensis. This species employs its tongue in a manner suggestive of chemosensory exploration, but it possesses modest peripheral chemosensory organs and reduced central representation of chemosensory target cell groups. Further, specific elements of exploratory behavior are affected differently by treatments that involve altering levels of stress-sensitive hormones, androgen, and central catecholamines. Such differential responses suggest that exploratory behavior is an ensemble of individual units, some of which are selectively sensitive to specific physiological elements of the stress response and of elevated arousal. PMID- 8477343 TI - Odorized air current trailing by garter snakes, Thamnophis sirtalis. AB - The response of adult red-sided garter snakes, Thamnophis sirtalis parietalis, to airborne odor trails was studied. An airtight T-maze was used, through which a constant airflow was drawn by a vacuum pump. The arms of the 'T' provided a choice between earthworm extract and distilled water. Experiment 1 tested the snake's responses to varying concentrations of earthworm extract. Snakes accurately trailed the extract at tested concentrations (0.0, 0.01, 0.1, 1, 10, 100%). At ten percent concentration, tongue-flick rate and speed along the maze increased significantly above lower levels, suggesting the existence of a threshold concentration. A correlation between mean tongue-flick rate and mean speed was demonstrated. Experiment 2 tested the effect of differentially blocked vomeronasal ducts on a snake's ability to trail. When both ducts were blocked, no trailing was observed, suggesting that vomeronasal stimulation is required. Blocking a single duct resulted in a significant number of snakes turning to the side of the functioning duct, suggesting that the tongue-vomeronasal system may function as a chemotaxic system. PMID- 8477344 TI - Chemosensory orientation behavior in juvenile sea turtles. AB - It has been widely believed for several decades that hatchling sea turtles imprint to chemical cues characteristic of their natal beach and use this information as part of a repertoire of mechanisms enabling their return to the same beach for mating and nesting. This has proven very difficult to test. Although the imprinting theory is conceptually simple, functionally it is quite complex. This involves not only chemical imprinting of nestlings but growth and migration to habitats where the adults are found, long-term memory of their earlier chemical exposure, reproductive maturation, and homing. A few studies have been conducted to examine these elements of the imprinting theory. Experiments involving the exposure of embryos and hatchlings to chemicals suggest that juvenile turtles 'imprint' to the chemical environment of their nest. This can be termed chemical imprinting. Loggerhead turtles, Caretta caretta, and ridley turtles, Lepidochelys kempi, appear to be attracted to chemicals (morpholine and natural seawater, respectively) to which they were exposed as embryos. The strongest support for chemical imprinting is that six-month-old green turtles, Chelonia mydas, exposed to either morpholine or 2-phenylethanol in the nest and for a period of time after hatching, respond similarly to the chemical to which they were exposed as nestlings. Although chemical imprinting does not 'prove' the imprinting theory of turtle homing, it is a necessary component of the theory not previously examined. PMID- 8477345 TI - Prairie rattlesnakes (Crotalus viridis) respond to rodent blood with chemosensory searching. AB - In Experiment I, homogenized rodent tissue was applied to the lips of prairie rattlesnakes (Crotalus viridis). This treatment produced elevated rates of tongue flicking compared to controls that received water, but the elevations seen following stimulation with homogenate were not as large as those seen after snakes struck prey. In Experiment II, water, rodent blood, and integumentary cues were applied to the lips of rattlesnakes, and only blood resulted in elevated rates of tongue flicking. We conclude that blood is a critical component of the homogenate. It is hypothesized that detection of blood during predatory strikes may be a causal element in the triggering of strike-induced chemosensory searching, a typical component of rattlesnake predatory behavior. PMID- 8477346 TI - Chemical recognition of kingsnakes by crotalines: effects of size on the ophiophage defensive response. AB - When confronted by an ophiophagous (snake-eating) kingsnake, venomous snakes of the subfamily Crotalinae exhibit a suite of defensive responses including head hiding, thrashing, and an unusual response termed 'body bridging'. Other responses observed, such as biting and 'freezing', are more general in nature and can occur in a variety of contexts. Various crotalines of differing sizes were tested for their responses to kingsnakes (Lampropeltis getulus). Responses of individuals were recorded for up to 18 months. The results indicate that, if habituation can be overcome by periodically allowing a kingsnake to confront but not harm the crotaline, the response is dependent on the size of the crotaline, in that smaller specimens (< 0.9 m) respond readily, while larger snakes (> 1.0 m) tend not to respond. The size of the kingsnake apparently does not have an effect on the crotaline response. These data appear to resolve apparent conflicts in the literature regarding whether certain species respond to ophidian ophiophages. In addition, hexane extracts of kingsnake skin were fractionated using an alumina column. The various fractions obtained were tested to determine which elicited the defensive response. Activity was found only in the most non polar fraction. Preliminary analysis by gas chromatography/mass spectrometry indicated that this fraction contained straight and branched, saturated and polyunsaturated long-chain hydrocarbons. PMID- 8477347 TI - Chemoreception in crocodilians: anatomy, natural history, and empirical results. AB - Anatomical and behavioral aspects of chemoreception in crocodilians are reviewed. Extant crocodilians possess valvular nostrils regulated by smooth muscles; paired nasal cavities, each with three conchae; and flaps closing the rear of the buccopharyngeal passage to channel inspired air through the nasopharyngeal duct. Olfaction is enhanced by gular pumping, whereby the floor of the pharynx is alternately lowered and raised to pulse air through the nasal cavity. Taste buds occur on the tongue, palate, and pharyngeal walls. Crocodilians in nature or in semi-natural enclosures locate distant carrion or concealed meat, implying chemoattraction to food. The American alligator exhibits underwater head-waving and mouth-opening in response to aqueous and chloroform extracts of meat. Alligators increase gular pumping in response to the scents of various meats, indicating that they detect food chemicals by olfaction. Paired gular and paracloacal glands on the integument of crocodilians are thought to produce pheromones. Juvenile crocodilians exhibit heightened gular pumping in response to airborne skin gland secretions. Observations of adults suggest that gular and paracloacal glands produce chemical signals used in mating and/or nesting activities, but behavioral responses to skin gland exudates are too poorly documented to ascribe pheromonal properties. PMID- 8477348 TI - Chemical and behavioral studies of femoral gland secretions in iguanid lizards. AB - Comparative studies on the chemistry and behavioral significance of femoral gland secretions in desert iguanas (Dipsosaurus dorsalis) and green iguanas (Iguana iguana) are reviewed. Field and laboratory studies suggest that femoral gland secretions function in conspecific recognition and range marking. In desert iguanas, secretions are of low volatility and may be detected initially using long-range ultraviolet visual cues. In contrast, green iguana secretions contain a diversity of volatile lipids and appear to be localized by chemoreception. Interspecific differences in femoral gland chemistry may reflect adaptations to the diverse climatic conditions of arid desert and tropical forest environments. PMID- 8477349 TI - Chemical ecology of the red-sided garter snake, Thamnophis sirtalis parietalis. AB - The red-sided garter snake, Thamnophis sirtalis parietalis is an ideal model for the study of chemical or pheromonal communication in vertebrates. Results of long term field and laboratory investigations of the chemical ecology of these unusual animals is summarized. These studies include a description of the characterization of the female attractiveness pheromone that serves to induce male courtship behavior. The male sex recognition pheromone system that identifies males as inappropriate individuals to court is also described. She males, individual males that are courted as if they were females, seem to possess semiochemical components intermediate to both males and females. Finally, investigations of the species-specific nature of these pheromones indicate that chemical differences exist in the methyl ketones of all species examined to date. PMID- 8477350 TI - Mechanisms of recognition in necrotrophic and biotrophic mycoparasites. PMID- 8477351 TI - Classification of heterobasidiomycetous yeasts: characteristics and affiliation of genera to higher taxa of heterobasidiomycetes. PMID- 8477352 TI - Antifungal effect of bean endochitinase on Rhizoctonia solani: ultrastructural changes and cytochemical aspects of chitin breakdown. AB - A chitinase, purified to homogeneity from ethylene-treated bean leaves, was applied to actively growing mycelial cells of Rhizoctonia solani to evaluate a potential antifungal activity. Light microscopic investigations at 30-min intervals following enzyme exposure revealed the induction of morphological changes such as swelling of hyphal tips and hyphal distortions. More precise information concerning fungal cell alteration was obtained by ultrastructural observation and cytochemical detection of chitin distribution in fungal cell walls. Chitin breakdown was found to be an early event preceding wall disruption and cytoplasm leakage. The large amounts of chitin present in the walls of control R. solani cells and the rapid chitin hydrolysis upon chitinase treatment lead us to suggest that this polysaccharide is one of the main components of this fungal cell wall and is readily accessible to chitinase, especially in the apical zone. By 60 min after enzyme treatment, labeled molecules were observed in the vicinity of some fungal cells, suggesting the release of chitin oligosaccharides from fungal cell walls. The antifungal activity of the bean chitinase on cells of R. solani grown in culture is discussed in relation to the potential of genetically modified transgenic plants to resist attack by R. solani through an antimicrobial activity in planta. PMID- 8477354 TI - Firearms control. PMID- 8477353 TI - Accumulation of factor F395 in nifNE mutants of Klebsiella pneumoniae. AB - The nifNE gene products of Klebsiella pneumoniae are required for the in vivo and in vitro synthesis of the iron-molybdenum cofactor (FeMo-co) of nitrogenase. Derepression of nifNE mutants for nitrogenase resulted in the accumulation of a small molecule, factor F395. Factor F395 is protein associated in vivo. We report here initial spectral characterization of this factor. PMID- 8477355 TI - Firearms control. PMID- 8477356 TI - Multicultural medicine. PMID- 8477357 TI - Balancing home and facility care. PMID- 8477358 TI - Physician infection and its consequences. PMID- 8477359 TI - Physician infection and its consequences. PMID- 8477360 TI - Prohibiting the sale of tobacco. PMID- 8477361 TI - Postpartum contraception: informed choice. PMID- 8477362 TI - Of AIDS and other plagues. PMID- 8477363 TI - Primary prevention of neural tube defects: notice from the HPB. PMID- 8477364 TI - The era of genetic medicine. PMID- 8477365 TI - Workshop on clinical practice guidelines: summary of proceedings. Department of Health Care and Promotion, Canadian Medical Association. PMID- 8477366 TI - Demand-side medical education: educating future physicians for Ontario. AB - Initiated by Associated Medical Services (AMS), Educating Future Physicians for Ontario is a 5-year collaborative project whose overall goal is to make medical education in Ontario more responsive to that province's evolving health needs. It is supported by AMS, the five universities with medical schools or academic health sciences centres and the Ontario Ministry of Health. The project's five objectives are to (a) define the health needs and expectations of the public as they relate to the training of physicians, (b) prepare the educators of future physicians, (c) assess medical students' competencies, (d) support related curricular innovations and (e) develop ongoing leadership in medical education. There are several distinctive features: a focus on "demand-side" considerations in the design of curricula, collaboration within a geopolitical jurisdiction (Ontario), implementation rather than recommendation, a systematic project evaluation plan and agreement as to defined project outcomes, in particular the development of institutional mechanisms of curriculum renewal as health needs and expectations evolve. PMID- 8477367 TI - Antituberculous drug resistance in Manitoba from 1980 to 1989. AB - OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period. As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs. DESIGN: Comparison of drug-resistant and non-drug resistant cases of tuberculosis. SETTING: Manitoba. PATIENTS: All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan. 1, 1980, and Dec. 31, 1989. MAIN OUTCOME MEASURES: Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases. The clinical course, including outcome of treatment, of all drug-resistant cases was described. RESULTS: Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians. Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada. Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had. Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin. Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs. Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period. The outcome of treatment in these individuals was poor, and they presented a particular public health problem. CONCLUSION: Resistance to one or more first line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease. PMID- 8477368 TI - Canadian outpatients and advance directives: poor knowledge and little experience but positive attitudes. AB - OBJECTIVE: To examine the knowledge of, previous experience with, attitudes toward and perceived barriers to completing advance directives among outpatients at two general medicine clinics. DESIGN: Cross-sectional questionnaire administered in face-to-face structured interviews. SETTING: General internal medicine outpatient clinics at a university teaching hospital. PATIENTS: One hundred and five adult outpatients who could communicate in spoken English and who consented to be interviewed. RESULTS: Of 167 patients approached, 58 were excluded because they could not communicate in spoken English, and 4 refused to participate. Of the remaining 105 patients, 17 (16%) knew about living wills, 12 (11%) about durable powers of attorney for health care and 4 (4%) about advance directives. Twenty-three (22%) had thought about their preferences for life sustaining treatment, 20 (19%) had discussed them, none had written them down, and 45 (43%) had thought about choosing a proxy. Sixty-one (58%) wanted to think about their preferences for treatment, 65 (62%) wanted to discuss them, 32 (30%) wanted to write them down, and 80 (76%) wanted to choose a proxy. The perceived barriers to completing an advance directive were inability to write, the belief that an advance directive was unnecessary, a fatalistic attitude, previous discussion of preferences, a desire to leave the decision to doctors, uncertainty about preferences, a desire to discuss preferences rather than document them, a desire to wait until the situation arose, a desire to write down preferences in the future and a desire to avoid thinking about preferences or advance directives. Respondents with more knowledge of life-sustaining treatments were more likely to want to complete an advance directive. CONCLUSIONS: Outpatients have positive attitudes toward advance directives, but their knowledge and experience are limited. These data underscore the need for patient education and for policies to eliminate the barriers to completing advance directives that patients face. PMID- 8477369 TI - Acute hypercalcemia and severe bradycardia in a patient with breast cancer. PMID- 8477370 TI - Some thoughts on medical education. 1929. PMID- 8477372 TI - The Association of Canadian Medical Colleges: Commemorating 50 years of the ACMC's contributions to medical education. PMID- 8477371 TI - The university, the hospital and the mission of the ACMC. PMID- 8477373 TI - The Association of Canadian Medical Colleges and how it grew. AB - The Association of Canadian Medical Colleges has evolved over the 50 years of its existence in ways that could not have been anticipated by its founders who, none the less, would approve of the mature adult their infant has become. Both undergraduate and postgraduate medical education in Canada are now on a firmer and more rational base than would have been possible without the guidance and direction provided by a national body capable of resisting regional and sectarian pressures. Credit for this achievement must go to those who were responsible for the creation of the secretariat in the early 1960s. The vision of Wendell Macleod, the first chief executive officer, led to the development of the association's strong research arm, and his charm and wisdom created a smoothly operating and loyal staff. The record of the organization is a tribute to its staff and to the wisdom and foresight of its Council of Deans and Board of Directors. PMID- 8477374 TI - ACMC: past, present and future. AB - In this article, the president of the Association of Canadian Medical Colleges (ACMC) and its director of research review the issues that have confronted ACMC since its inception: the founding of ACMC; development of the clinical teaching unit; creation of the Medical Research Council and expansion of the research mission; the Royal Commission on Health Services and the founding of new faculties of medicine; ACMC's in-house research program; accreditation and ACMC's links with medical education in the United States; and French-language medical education in Canada. The review points out the perennial nature of many of these issues, and how often perceived solutions to the problems later become problems themselves. It ends on the optimistic note that ACMC can successfully meet the challenges of the future. PMID- 8477375 TI - Canadian medical schools before ACMC. AB - The earliest medical schools were established to supplement apprenticeship, the only route to practice available in colonial Canada. By 1885, eight medical schools were trying to accommodate the volume of new scientific information flowing from Europe. In 1910, when Flexner evaluated the schools against the Johns Hopkins model, some were woefully deficient, but by 1928 all had achieved Class A rating. The 1921 discovery of insulin in Toronto gave impetus to scientific research and, possibly, influenced the formation and funding of the National Research Council in 1934. Clinical specialization expanded, leading in 1929 to the establishment of the Royal College of Physicians and Surgeons of Canada to accredit training and certify graduates. The Association of Canadian Medical Colleges was formed at a meeting of deans to discuss a federal offer of funding and to accelerate the graduation of physicians for the war effort. PMID- 8477376 TI - Universities and medical schools: reflections on a half-century of Canadian medical education. AB - After 50 years of accelerated development, universities and medical schools have entered a period of uncertainty and instability. The Flexnerian paradigm of medical education, rooted in biomedical science and conducted under the aegis of a university, reached its apotheosis by the late 1960s and the early 1970s. Fuelled by the introduction of comprehensive, government-sponsored health care insurance and advances in technology, the demand for health care professionals and for access to facilities increased sharply. Medical education, research and advanced clinical services expanded dramatically aided by the emergence of academic health sciences centres and accompanied by a wave of medical curriculum reform. Now medical schools must strike a dynamic balance in responding to the continued expansion of knowledge and technology, the demand for social equity and the exigencies of prolonged fiscal constraint. They must also balance the biological and sociological approaches to medicine in establishing the foundations for the future development of Canadian medical education. PMID- 8477377 TI - The academic medical centre: an idea whose time has come. AB - Interdependence of faculties of medicine or health sciences and teaching hospitals is central to the academic medical centre's three "products": education, research and clinical service. Whether a voluntary association, partnership, joint venture or single entity, the strength of the association of member institutions must lie in mutual dependency. With the potential of reducing costs and increasing effectiveness through administrative efficiency and rationalization, especially of planning and setting priorities, the academic medical centre can outstrip its individual member institutions in contributing to the solution of Canada's present and future challenges in health care. PMID- 8477378 TI - The role of academic health sciences centres in international health. AB - For many years, Canadian academic health science centres have been active in international health. This brief review describes the activities of the Canadian Society for International Health, the Canadian University Consortium for Health in Development, and McGill, McMaster and Ottawa universities. Three principles are derived from these examples. Health must be placed in the broader context of development, and international health initiatives must be intersectoral. Canadian universities can make a distinctive and important contribution to health and development internationally, but this requires a clear commitment to scientific excellence and social responsibility. Finally, Canadian institutions, as representatives of the North, have much to learn through collaboration and partnerships with institutions in the South. PMID- 8477379 TI - An American's view of Canadian medical education. AB - Undergraduate medical education in Canada and the United States is remarkably similar, except for the fact that Canadian medical schools are supported by their provincial governments. However, the systems diverge sharply at the postgraduate level. In Canada, the number and specialty mix of residents are negotiated by medical schools in response to educational and social needs; in the United States, these factors are largely determined by hospital service needs. The Canadian systems of accreditation, certification and payment for medical education after graduation are much simpler than those of the United States, and the accreditation and certification systems are more objective. In addition, the US system promotes subspecialization and a costly specialty imbalance, whereas Canada's system has achieved an appropriate balance of specialists and generalists. In general, Canadian medical education appears to be simpler, more accountable and more socially responsive. PMID- 8477380 TI - History of specialty residency funding in Canada. AB - Specialty residency training in Canada has evolved from its origin in teaching hospitals through an era dominated by universities to the present when public accountability is emerging as a dominant influence. The predominant educational strategies, including experimental learning, role modelling, continuum of training, independent thinking, self-directed learning and research experiences, have been influenced by the diversity of roles expected of the resident, including that of an employee, a student, a teacher and, more recently, a part of the policy instrument of governments in controlling physician resources. PMID- 8477381 TI - Academic family medicine in Canada. AB - Fifty years ago family practice in Canada had no academic presence. Stimulated by a number of general practitioners and with the support of the Canadian Medical Association, the College of General Practitioners of Canada (CGPC) was founded in 1954. In 1962, conferences on education for general practice attended by the Association of Canadian Medical Colleges and the CGPC led to pilot postgraduate residencies in family practice supported by Department of National Health and Welfare. The first certification examination was held in 1969 and, by 1974, all Canadian medical schools had a family medicine residency program. Today departments of family medicine contribute substantially to undergraduate education in all 16 schools. In Canada, the medical profession, governments and the medical schools have demonstrated the importance they place on appropriate education for family physicians. PMID- 8477382 TI - The clinical teaching unit in transition. AB - The clinical teaching unit (CTU), a distinctively Canadian concept, has served Canadian academic medicine well over the past 30 years. Times have changed considerably since the concept was first defined by the Association of Canadian Medical Colleges in 1962. Many proposals and ideas of Evans, Chute and Morley in their description of the CTU, clinical education and the practice of medicine remain relevant today. The concept of learning by doing, under supervision, in a relatively controlled academic environment is still valid. However, we must either expand our concept of the traditional CTU to make it consistent with the contemporary broad practice of medicine or maintain the current model as complementary, but not necessarily central, to an expanded paradigm of clinical education. PMID- 8477383 TI - A student-centred, problem-based curriculum: 5 years' experience. AB - In 1987, the University of Sherbrooke's school of medicine implemented a student centred, problem-based learning (PBL) curriculum. The experience of the first 5 years is reviewed; program goals, the schedule of learning activities, the instructional format and assessment of student learning are described. The new program is more demanding of teachers and requires better faculty training in pedagogy. No new financial resources have been available. The preclinical reform has led to revision of the clerkship, where sessions on clinical reasoning are now based on the PBL philosophy. Student reactions to the program are reported. The Sherbrooke experience has demonstrated that it is both possible and feasible to shift from a traditional to a problem-based curriculum. PMID- 8477384 TI - Canadian experience with structured clinical examinations. AB - The use of structured clinical examinations to improve the evaluation of medical students and graduates has become significantly more common in the past 25 years. Many Canadian medical educators have contributed to the development of this technique. The Canadian experience is reviewed from the introduction of simulated standardized patients and objective-structured clinical examinations to more recent developments and the use of such examinations for licensure and certification. PMID- 8477385 TI - Health research in Canada: a shifting paradigm. AB - A personal review of medical research in Canadian medical schools over the past 25 years reveals extraordinary contributions. Over this time, medical research evolved from a by-product of faculty members to a commitment that determines the future success of a medical faculty. The increasing competition for health research funding and the high standards created internationally have changed the way research is organized in our medical faculties. Current trends include a move toward group and thematic research, an increased role of research institutes and the development of strategic partnerships with industry. Because of the need for more planning and more critical and timely review of research efforts, the benefits of collaboration enhance the quality and competitiveness of a medical faculty. A broadened vision of the Medical Research Council and provincial foundations and the need to increase resources for research foreshadow even greater change. PMID- 8477386 TI - Canadian medical education: 50 years of innovation and leadership. AB - Over the past 50 years, many Canadian medical educators have pursued ideas and visions, as individuals in the 1950s and 1960s and later in partnership with various national bodies. Relations between universities and national medical organizations have been productive in dealing with issues of postgraduate education and clinical assessment, in particular. From 1970 to 1990, strong education offices and formally trained educators led to many successes in the areas of research in cognition, continuing medical education and clinical assessment. Canadian medical education has now achieved international recognition for its work in all aspects of the continuum of the physician's education through vision, initiative and cooperation. PMID- 8477388 TI - Life in the ER: wild nights, mounting stress and mid-40s burnout. PMID- 8477387 TI - Pondering the future. AB - Despite growing tensions as the Canadian health care system evolves, the system will survive over the next decade and strengthen its societal objectives, sometimes dragging physicians along. With the shift of the intellectual centre away from the universities, research and researchers will find funding security but career insecurity in the private sector. The independent investigator will become rare as "big science" becomes the norm, and basic science departments will have a decade of confusion as they struggle for a new place in the renewed medical schools. The move toward problem-based, community-oriented medical education will be completed, clinical faculty will become salaried and the smaller numbers of graduates will be more controlled in their practices. Medicine as a profession will adopt a renewed philosophical framework and will broaden in its scope to the benefit of Canadians. PMID- 8477389 TI - Move to decentralize FP residencies may help solve MD maldistribution problems. PMID- 8477390 TI - Getting them off nicotine. PMID- 8477391 TI - "TB voyages" into High Arctic gave MDs a look at a culture in transition. PMID- 8477392 TI - A case for caring. PMID- 8477393 TI - Brucellosis: a medical rarity that used to be common in Canada. PMID- 8477394 TI - Many of Britain's disillusioned doctors are leaving medicine behind. PMID- 8477395 TI - Experiences in China shed new light on Eastern medicine. PMID- 8477396 TI - Cultural awareness in the context of terminal illness. AB - While cultural awareness provides direction for planning effective nursing interventions at all stages of health and illness, this article specifically addresses applications for patients who are terminally ill. Professional nurses encounter unique challenges in caring for terminally ill patients. Assisting patients to achieve an "appropriate death" requires communication and collaboration among patients, family members, and professional caregivers. Since patients and their families represent many systems of complex beliefs and values, nurses must be aware of the impact of cultural pluralism on nursing assessment and intervention in terminal illness. Reordering priorities and redistributing resources have been identified as new approaches in caring for terminally ill patients and their families. Two concepts that cut across all cultural boundaries are loss and grief. Expressions of loss and grief take on a variety of forms among members of diverse cultures. It is critical that nurses recognize, understand, and respect each family's culture-specific patterns with regard to terminal illness. Understanding the culture will lead to the design of culturally appropriate nursing care for patients and families. Culture brokerage is defined as an act of translation, where messages, instructions, and belief systems are exchanged between cultural groups. This strategy has the potential to increase understanding among those with diverse cultural backgrounds, resulting in increased patient/family satisfaction within the supportive care setting. Consonance between patients' needs and nurses' understanding of those needs will lead to more culturally appropriate intervention strategies. PMID- 8477397 TI - Oncology nurse and physician attitudes toward aggressive cancer treatment. AB - Oncology nurses (n = 57) and oncology physicians (n = 40) employed in the same hospital completed the Cancer Attitude Questionnaire. Significant differences (p < or = .001) between nurse and physician attitudes were evident on the two major subscales addressing the issues of (a) aggressiveness of treatment/de-emphasis of socioemotional aspects of care and (b) the importance of patient-family attitudes. Physicians' attitudes were significantly more favorable on the first subscale; nurses' attitudes were significantly more favorable on the second. Implications of these findings as indicators of potential nurse-physician conflict are discussed. PMID- 8477398 TI - A nursing intervention for early detection of spinal cord compressions in patients with cancer. AB - This article reviews the current literature regarding spinal cord compression including its prevalence and presenting signs and symptoms; increases an awareness of the potentially severe effects of spinal cord compression; and describes a model for patient educational intervention focusing on early warning signs of spinal cord compression. With increased understanding of the nature and effects of spinal cord compression, nurses may effectively intervene to minimize the severity of the neurological deficits. PMID- 8477399 TI - Reducing the incidence of stomatitis using a quality assessment and improvement approach. AB - Stomatitis occurs in approximately 40% of the patients receiving systemic administration of chemotherapy and cancer treatments such as radiation to the head and neck. The presence of stomatitis affects the course of treatment and a patient's quality of life. An oncology nursing unit developed a quality assessment and improvement indicator addressing stomatitis. Oral cavity screening, dental consultations, oral care techniques, and patient teaching were included in the nursing interventions, which resulted in a marked reduction of new cases of stomatitis. PMID- 8477400 TI - Evaluation of high-risk smoking practices used by the homeless. AB - The purpose of this study was to evaluate the prevalence of high-risk smoking practices in a homeless population. High-risk cigarette smoking practices include misuse of tobacco products or alternative methods of cigarette smoking that increase the likelihood of ingestion of toxic substances and infectious agents that can potentiate the hazards associated with cigarette smoking. An 84-item questionnaire was developed by the researcher to measure these practices. Fifty six male and three female homeless people were interviewed in downtown Los Angeles. The most common high-risk smoking practices were cigarette sharing (86%); smoking cigarettes remade from discarded cigarette butts and filters (71%); smoking cigarettes remade by others (63%); smoking discarded cigarette butts (63%); blocking filter vents (24%); using things other than tobacco, such as discarded cigarette filters and drugs, in remaking cigarettes (22%); and smoking discarded cigarette filters (19%). These high-risk smoking practices pose a greater risk of exposure to toxins trapped in filters and tobacco remains and increase the threat of infectious disease transmission. The long-term effects of high-risk smoking practices among the homeless have potential economic implications for society. PMID- 8477401 TI - The role of the data manager in clinical cancer research. An opportunity for nurses. AB - A clinical trial is a research study conducted in humans and designed to answer specific questions using scientifically controlled methods. These trials require considerable effort to assure that the data obtained are reliable, reproducible, and readily available. Data managers play a key role in this research effort. A nurse with a clinical background, computer knowledge, and some experience in the research environment is well suited for the role of data manager. The data manager performs a variety of tasks in this position that will enhance the quality of the data gathered in a research study. These responsibilities include designing forms, monitoring protocol accrual, abstracting data, entering data onto protocol-specific forms and/or specifically designed computerized data-entry screens, assuring the quality and the integrity of the data, and providing investigators with interim and summary reports. In addition, the data manager can be responsible for the management of a computerized clinical data base system, including the training of users and the designing of basic reports for the investigators. A nurse, functioning as a data manager, who understands research methodology, is detail oriented, and is well organized, could be a valuable asset to the clinical trials team in the successful management of any clinical study. PMID- 8477402 TI - Safe tan. An oxymoron. AB - Skin cancer may be a very preventable malignancy, yet the incidence is increasing at an epidemic rate. Solar ultraviolet radiation is the major carcinogenic agent. The expression "a good healthy tan" is a contradiction; tanning is the biological process of the skin responding to injury. Regular use of a properly selected and applied sunscreen is one of the essential primary prevention strategies for reducing the incidence of skin cancer. Nurses can be instrumental in helping patients/clients understand the dangers of suntanning and the need for protection against solar ultraviolet radiation (UVR). PMID- 8477403 TI - Cancer chemotherapy: intravenous administration. PMID- 8477404 TI - Development of an intervention to restore attention in cancer patients. AB - Developing interventions to maintain or restore attentional capacity during demanding phases of illness will help promote effective functioning in people with cancer. This study tested the effects of an experimental intervention aimed at maintaining or restoring attentional capacity in 32 women during the 3 months after surgery for localized (Stage I or II) breast cancer. The intervention was designed to minimize or prevent attentional fatigue through regular participation in activities that engage fascination and have other restorative properties. Attentional capacity was assessed using objective and subjective measures at four time points, approximately 3, 18, 60, and 90 days after breast cancer surgery. After the first observation, subjects were randomly assigned to receive the intervention (n = 16) or not to receive intervention (n = 16). Repeated measures ANOVA showed a significant interaction of experimental intervention and time on attentional capacity. Specifically, subjects in the intervention group showed significant improvement in attentional capacity over the four time points, while the nonintervention group showed a pattern of inconsistent performance over time. Findings suggest that nurses can intervene to maintain or restore attentional capacity in women after surgery for localized breast cancer. The theoretical basis for further development of attention-restoring interventions in patients with cancer is discussed. PMID- 8477405 TI - The use of therapeutic massage as a nursing intervention to modify anxiety and the perception of cancer pain. AB - The purpose of this exploratory study was to examine the effects of therapeutic massage (consisting of effleurage, petrissage, and myofascial trigger point therapy) on pain perception, anxiety, and relaxation levels in hospitalized patients experiencing significant cancer pain. Thirty minutes of therapeutic massage was administered on two consecutive evenings to nine hospitalized males diagnosed with cancer and experiencing cancer pain. The subjects' self-reports of pain and relaxation (measured by Visual Analogue Scales) as well as anxiety (measured by the Spielberger State Anxiety Inventory) were recorded before and immediately after the intervention. The objective physiologic measures of heart rate, respiratory rate, and blood pressure were obtained before, immediately after, and, finally, 10 min after the massage intervention. Massage therapy significantly reduced the subjects' level of pain perception (average = 60%) and anxiety (average = 24%) while enhancing their feelings of relaxation by an average of 58%. In addition to these subjective measures, all physiological measures (heart rate, respiratory rate, and blood pressure) tended to decrease from baseline, providing further indication of relaxation. In conclusion, although the exact mechanism is not known, therapeutic massage is a beneficial nursing intervention that promotes relaxation and alleviates the perception of pain and anxiety in hospitalized cancer patients. PMID- 8477406 TI - Pharmacological basis of immunotherapy in autoimmune diseases. AB - The clinical development of immunomodulatory agents for the treatment of autoimmune diseases is an arduous process. This can be explained by the fact that the true pathogenic mechanism of the disease(s) is unknown. Moreover, the properties and pharmacokinetic profile of these immunomodulatory agents are different from other classic therapeutic compounds. The aim of this brief review is to discuss a number of general aspects of the clinical pharmacology of i.v. immune globulin as well as more recent immunotherapeutic approaches such as anti cytokine therapy, which are currently being applied in the immunotherapy for neurologic and rheumatic autoimmune disorders such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and rheumatoid arthritis. A better understanding of the interaction of the therapeutic compound and the host immune response, the knowledge of its kinetic profile, and the development of surrogate markers of clinical efficacy should help in designing randomized and blinded clinical trials that will ultimately determine the optimal therapeutic regimen. PMID- 8477407 TI - Reproducibility of motor effects induced by successive subcutaneous apomorphine injections in Parkinson's disease. AB - We performed a crossover study of apomorphine-induced motor response reproducibility in 10 parkinsonian patients with the "on-off" phenomenon. On 2 separate days, each patient received two successive identical s.c. apomorphine injections, the second injection being randomly administered either 10 or 80 min after the end of the first apomorphine-induced motor benefit. Latency (12.3 +/- 4.5 min) and duration (61.9 +/- 13.3 min) of motor effects were similar in all tests. A transient worsening of the parkinsonian state after a motor improvement induced by apomorphine occurred in most of the patients. Therefore, the duration and severity of the "off" period after a motor improvement does not seem to influence the efficacy of a second apomorphine administration. PMID- 8477408 TI - Effects of bromocriptine in human narcolepsy. AB - Bromocriptine, a preferential D2 receptor agonist, was administered to six human narcoleptic patients during a double-blind, cross-over study. Laboratory sessions consisted of two all-night polysomnographic recordings and three daytime tests of vigilance: the Analogue Vigilance Scale (AVS), the Maintenance of Wakefulness Test (MWT), and the Four-Choice Reaction Time Test (FCRTT). No change in nocturnal sleep organization, daytime somnolence, or psychomotor performance was observed during bromocriptine administration. Periodic limb movements in sleep (PLMS) were significantly reduced during bromocriptine condition. These results suggest that D2 receptors are unlikely to play a major role in the physiopathology of human narcolepsy, and support the hypothesis that dopaminergic mechanisms are involved in PLMS. PMID- 8477409 TI - Response to L-DOPA in multiple system atrophy. AB - A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients. PMID- 8477410 TI - The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. AB - We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Single increasing oral doses of entacapone (50-400 mg) were administered concomitantly with a single oral dose of levodopa/carbidopa (100/25 mg). The subjects were treated with carbidopa (100 mg t.i.d.) for 1 day prior to the administration of study drugs. Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4 dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations. Entacapone dose-dependently increased the area under the plasma concentration time curve (AUC) of levodopa; the increase was 65% after the 400 mg dose of entacapone. Neither Cmax nor Tmax of levodopa was statistically significantly influenced by entacapone. Entacapone dose-dependently decreased the AUC of 3-OMD, maximally by 58%. The AUC of DOPAC was statistically significantly increased but no change in the AUC of HVA was observed after entacapone. No drug-related adverse events or hemodynamic effects were observed. The in vivo biochemical effects of entacapone indicate that it is an orally active COMT inhibitor and that it may improve the therapeutic efficacy of levodopa in Parkinson's disease. PMID- 8477411 TI - Relation between clinical efficacy and pharmacokinetic parameters after sublingual apomorphine in Parkinson's disease. AB - Apomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the "on" period than 0.6 mg/kg (0.3 mg/kg: 24.2 +/- 14.6 min; 0.6 mg/kg: 86.7 +/- 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 +/- 3.4 min; 0.6 mg/kg: 38.3 +/- 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 +/- 3.2 ng/ml; 0.6 mg/kg: 22.7 +/- 3.6 ng/ml; p < 0.01; AUC: 0.3 mg/kg: 929 +/- 109 ng/ml/min; 0.6 mg/kg; 2,277 +/- 209 ng/ml/min; p < 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, and Cmax (r = 0.86, p < 0.01 for AUC; r = 0.63, p < 0.05 for Cmax). These results show that sublingual apomorphine could be of interest in the treatment of "off" phases in parkinsonian patients with motor fluctuations. PMID- 8477412 TI - A pilot controlled study of fluoxetine for obsessive-compulsive symptoms in children with Tourette's syndrome. AB - We carried out a double-blind, randomized, parallel-groups clinical trial of fluoxetine (20-40 mg/day) and placebo in 11 children with Tourette's syndrome (TS) and associated obsessive-compulsive symptoms (OCS). The treatment period lasted 4 months. No significant differences between treatment groups were observed for measures of OCS. Fluoxetine therapy, however, was associated with a trend toward some improvement in tic severity, attentional abilities, and social functioning. Given these observations and the limitations of this pilot study, which include selection biases, small sample size, and significant placebo effects, the efficacy of fluoxetine in children with TS deserves further larger scale investigation. PMID- 8477413 TI - Encephalopathy associated with bismuth subgallate therapy. AB - A 74-year-old man developed paranoid ideation, memory impairment, and defective gustatory and olfactory function while on bismuth subgallate therapy for use as a colostomy deodorant. Twenty-four-hour urine bismuth was elevated at 889 micrograms/day, and whole blood bismuth concentration was 67 micrograms/L. The patient improved after discontinuation of bismuth subgallate; there was resolution of paranoid behavior and gustatory and olfactory functions improved. Follow-up whole blood bismuth concentration was 21 micrograms/L 4 weeks after cessation. Altered gustatory and olfactory function have not been previously reported with bismuth intoxication. PMID- 8477414 TI - Immunopharmacologic therapy in myasthenia gravis. AB - Immunotherapy is frequently employed in treatment of patients with myasthenia gravis. Different regimens are not based entirely on controlled or comparative studies. There are few clear guidelines for choosing a particular immunomodulating agent and timing of its introduction. In this article, we have tried to summarize known information about the immunopharmacologic agents used for the treatment of patients with myasthenia gravis. PMID- 8477415 TI - Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking. AB - The B16-BL6 melanoma, like most spontaneously arising tumors, is poorly immunogenic and expresses low levels of major histocompatibility complex (MHC) antigens. Treatment of cells of this tumor in vitro by hydrostatic pressure in the presence of adenosine 2',3'-dialdehyde (oxAdo), a membrane-impermeant crosslinker, caused elevated projection of MHC and a specific tumor antigen as demonstrated by flow-cytometric analysis. Maximum projection of both the MHC and the tumor antigens could be reached by application of 1200 atm for 15 min in the presence of 20 mM oxAdo. It is not yet clear whether this passive increase in availability of antigens on the cell surface originated from a dormant pool of antigens in the plasma membrane or from pressure-induced fusion of antigen-rich intracellular organelles (e.g. the endoplasmic reticulum). The immunogenic properties of the antigen-enriched B16-BL6 cells are described in the following paper. PMID- 8477416 TI - Induction of cell-mediated immunity against B16-BL6 melanoma in mice vaccinated with cells modified by hydrostatic pressure and chemical crosslinking. AB - In the preceding paper we have demonstrated an increase in presentation of both major histocompatibility complex antigens (MHC) and a tumor-associated antigen of the weakly immunogenic B16 melanoma by a straight-forward technique. The method consists in modulating the tumor cell membrane by hydrostatic pressure and simultaneous chemical crosslinking of the cell-surface proteins. In B16-BL6 melanoma, the induced antigenic modulation was found to persist for over 48 h, which permitted the evaluation of the ability of modified B16-BL6 cells to induce immunity against unmodified B16-BL6 cells. In the present study, we have shown that a significant systemic immunity was induced only in mice that were immunized with modified B16-BL6 melanoma cells, whereas immunization with unmodified B16 BL6 cells had only a marginal effect when compared to the results in control sham immunized mice. The induced immunity was specific since a single immunization affected the growth of B16-BL6 tumors but had no effect on MCA 106, an antigenically unrelated tumor. The addition of interleukin-2 to the immunization regimen had no effect on the antitumor responses induced by the modified B16-BL6 cells. The cell-mediated immunity conferred by immunization with treated B16-BL6 cells was confirmed in experiments in vitro where splenocytes from immunized mice could be sensitized to proliferate by the presence of B16-BL6 cells. In addition, the altered antigenicity of these melanoma cells appeared to correlate with their increased susceptibility to specific effectors. Thus, 51Cr-labeled B16-BL6 target cells, modified by pressure and crosslinking, in comparison to control labeled target cells, were lysed in much greater numbers by effectors such as lymphokine activated killer cells and allogeneic cytotoxic lymphocytes (anti-H-2b), while such cells remained resistant to lysis by natural killer cells. Our findings indicate that the physical and chemical modifications of the tumor cells that are described here may be considered as a simple yet effective method for the preparation of tumor vaccines, which could be applied in tumor-bearing hosts. PMID- 8477417 TI - Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2. AB - Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogenic tumor cells. A preferential lysis of autologous melanoma cells was obtained in long-term cultures of 7/13 cases (54%), while the remaining ones showed a major-histocompatibility-complex unrestricted, lymphokine-activated-killer(LAK)-like activity at the time of in vivo injection. Sixteen patients with metastatic melanoma were infused with TIL (mean number: 6.8 x 10(9), range: 0.35 x 10(9)-20 x 10(9)) and IL-2 (mean dose: 130 x 10(6) IU, range: 28.8 x 10(6)-231 x 10(6) IU); 1 complete and 3 partial responses were observed in 12 evaluable patients (response rate 33%). In all responding patients, injected TIL showed an in vitro preferential lysis of autologous tumor cells, while in no cases were TIL with LAK-like activity associated with a clinical response. The mean autologous tumor cytotoxic activity of TIL at the time of in vivo injection was significantly higher in responding patients in comparison to nonresponding ones, suggesting that a marked and preferential cytolysis of autologous tumor cells is associated with the therapeutic efficacy of TIL. PMID- 8477418 TI - Heterogeneous binding and killing behaviour of human gamma/delta-TCR+ lymphokine activated killer cells against K562 and Daudi cells. AB - Effector-target conjugates, formed by coincubation of lymphokine-activated killer (LAK) cells with either K562 or Daudi cells, were separated from single cells by Percoll sedimentation. The occurrence of various CD molecules (CD3, CD56, CD57, CD16, gamma/delta-TCR) was compared in both fractions. Only LAK cells expressing the gamma/delta T cell receptor (TCR) were found in a significantly increased percentage in fractions containing conjugates indicating that gamma/delta-TCR+ LAK cells were preferably bound to target cells at the time of separation. In order to determine whether gamma/delta-TCR+ LAK cells also show a preferred killing activity against the targets, cultures enriched with or depleted of gamma/delta-TCR+ cells were established. Against K562 cells, gamma/delta-TCR(+) enriched cultures showed a greatly reduced killing activity compared to LAK bulk cultures or cultures depleted of gamma/delta-TCR+ cells. Using Daudi cells as targets the enriched fraction revealed a slightly increased killing activity compared to bulk cultures or depleted fractions. Preincubation of gamma/delta TCR+ LAK cells with anti-gamma/delta or anti-CD3 mAb resulted in a distinct increase of the killing activity against K562 cells, but in only a slightly enhanced activity against Daudi cells. It is postulated that gamma/delta-TCR+ LAK cells use the same adhesion mechanism for both targets but that only Daudi cells express a specific ligand for the gamma/delta-TCR. Occupation of the gamma/delta TCR/CD3 complex by mAb, however, seems to substitute for the absent epitope on K562 cells by eliciting stimulatory signals in gamma/delta-TCR+LAK cells which, in combination with the binding stimulus, trigger cytolytic activity. PMID- 8477419 TI - Development of a bispecific monoclonal antibody against a gallium-67 chelate and the human melanoma-associated antigen p97 for potential use in pretargeted immunoscintigraphy. AB - A bispecific monoclonal antibody (bsmAb) has been developed against the human melanoma-associated antigen p97 and an octahedral gallium chelate (Ga-HBED) using the hybrid hybridoma technology. As tetradomas were expected to produce a maximum of ten different molecular species of immunoglobulins, the bispecific antibody was purified from this mixture by consecutive protein A affinity and cation exchange chromatographic techniques. Although it was established by sodium dodecyl sulphate/polyacrylamide gel electrophoresis that the heavy (H) and light (L) chains of the two parental immunoglobulins were mismatched in the bispecific antibody, results from cell enzyme-linked immunosorbent assay indicated significant dual specific binding to both the melanoma cells and 67Ga-HBED. Other in vitro techniques further confirmed that the bsmAb Bi 5-56-II-17 still retained about 30%-40% simultaneous binding capacity to both the antigens, as would have been expected in a bsmAb that has ideally matched H and L chains. Preliminary in vivo experiments using nude mice bearing the human melanoma xenografts showed that the bsmAb Bi 5-56-II-17 was able to target the radioactive gallium chelate to the tumours twice as efficiently compared to the monospecific, bivalent gallium chelate antibody. PMID- 8477420 TI - Dentistry as portrayed in motion pictures and television. PMID- 8477421 TI - Dental finances improved in the 1980s. PMID- 8477422 TI - Insurance Reimbursement Matters. The role of the dental team in the evaluation and treatment of a new or recall patient. PMID- 8477423 TI - Methicillin-resistant Staphylococcus aureus: a crisis in infection control. PMID- 8477424 TI - Apex locators: a systematic approach for usage. PMID- 8477425 TI - Choice of dental practice is indicative of personality traits. PMID- 8477426 TI - Anterior tooth replacement using a two-component resin-bonded bridge. PMID- 8477427 TI - Management of child behavior in the dental environment. PMID- 8477428 TI - Desktop publishing: how to use it in your practice. PMID- 8477429 TI - Clinical criteria used to select an articulator. PMID- 8477430 TI - An unusual complication resulting from a Gow-Gates mandibular block. PMID- 8477431 TI - The telephone: friend or foe. PMID- 8477432 TI - Tuberculosis in the 1990s: current implications for dentistry. PMID- 8477433 TI - Office sterilization and asepsis procedures (OSAP) research foundation. PMID- 8477434 TI - Update on heat sterilization and sterilization monitoring. PMID- 8477435 TI - Selection and use of threaded pins: a review. PMID- 8477436 TI - Procedure-specific infection-control recommendations for dentistry. PMID- 8477437 TI - Partial glossectomy--a treatment for lymphangioma of the tongue. PMID- 8477438 TI - Dental air-powered handpieces: selection, use, and sterilization. PMID- 8477439 TI - Care and repair of porcelain veneers. PMID- 8477440 TI - Infection control in the dental laboratory: concerns for the dentist. PMID- 8477441 TI - X-rays: detailed answers to frequently asked questions. PMID- 8477442 TI - T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases. PMID- 8477443 TI - Parallel DNA triplexes, homologous recombination, and other homology-dependent DNA interactions. PMID- 8477444 TI - Mice with a null mutation of the TGF alpha gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. AB - Mice homozygous for a disrupted transforming growth factor alpha (TGF alpha) gene are healthy and fertile, although some older mice show evidence of corneal inflammation. In contrast with TGF alpha +/- and +/+ animals, TGF alpha -/- mice have a pronounced waviness of the coat. Histological examination of the skin from TGF alpha -/- mice reveals a dramatic derangement of hair follicles. Mice with a disrupted TGF alpha gene also have curly whiskers, first evident on the day of birth. The phenotype of TGF alpha -/- mice is remarkably similar to that of the mouse mutant waved-1 (wa-1). Offspring resulting from crosses between TGF alpha /- and wa-1 mice display the curly whisker-coat phenotype, indicating that the basis of the wa-1 phenotype is a mutation in the TGF alpha gene. These observations suggest that TGF alpha plays a pivotal role in determining skin architecture and in regulating hair development. PMID- 8477445 TI - TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. AB - To explore the physiological roles of transforming growth factor alpha (TGF alpha), we disrupted the mouse gene by homologous recombination in embryonic stem cells. Homozygous mutant mice were viable and fertile, but displayed pronounced waviness of the whiskers and fur, accompanied by abnormal curvature, disorientation, and misalignment of the hair follicles. Homozygous and, to a lesser extent, heterozygous mice displayed eye abnormalities of variable incidence and severity, including open eyelids at birth, reduced eyeball size, and superficial opacity. Histological examination revealed eyelid and anterior segment dysgenesis, corneal inflammation and scarring, and lens and retinal defects. Although TGF alpha deficiency affected skin and eyes, wound healing in these tissues was not impaired. Similar hair and eye defects have been previously associated with the recessive mutation waved-1 (wa-1), and Northern analysis revealed reduced expression of TGF alpha in wa-1 mice. Crosses between wa-1 homozygotes and TGF alpha-targeted mice confirmed that wa-1 and TGF alpha are allelic. PMID- 8477446 TI - The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. AB - Apoptosis plays an important role in regulating cell numbers in a wide variety of tissues during development. The product of the bcl-2 gene inhibits apoptosis in certain cells of the myeloid and lymphoid lineages and is expressed in many cells that have an extended life span. To assess the role of bcl-2 in neuronal apoptosis, we microinjected a bcl-2 expression vector into neurotrophic factor deprived embryonic neurons. Sensory neurons that depend for survival on one or more members of the nerve growth factor family of neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3) were rescued by bcl-2, whereas ciliary neurotrophic factor (CNTF)-dependent ciliary neurons were not. Sensory neurons, however, became refractory to bcl-2 after exposure to CNTF. These findings indicate that at least two death pathways operate in neurons that are distinguished by their susceptibility to bcl-2. Neurons may die by either pathway, depending on the factors to which they have been exposed. PMID- 8477447 TI - Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. AB - Adenovirus contains a heterodimeric protein complex consisting of 186 kd fiber protein that mediates high affinity virus attachment to cells and a 400 kd pentavalent subunit (penton base) that contains five Arg-Gly-Asp sequences, implying a role for integrins in adenovirus infection. We demonstrate that the vitro-nectin-binding integrins alpha v beta 3 and alpha v beta 5 promote viral infection in a novel way since antibodies against these receptors or soluble penton base block virus internalization without affecting attachment. Moreover, adenovirus binds to cultured cells lacking alpha v integrins but fail to become internalized, thus restricting infection of these cells. Transfection of alpha v( ) cells with a cDNA encoding alpha v results in the expression of integrins alpha v beta 3 and alpha v beta 5 and allows virus internalization and infection. These data indicate that adenovirus attachment and uptake into cells are separate but cooperative events that result from the interaction of distinct viral coat proteins with a receptor for attachment and alpha v integrin receptors for internalization. PMID- 8477448 TI - An alternative pathway for yeast telomere maintenance rescues est1- senescence. AB - Yeast cells lacking a functional EST1 gene show progressive shortening of the terminal G1-3T telomeric repeats and a parallel increase in the frequency of cell death. Although the majority of the cells in an est1- culture die, a minor subpopulation survives the potentially lethal consequences of the est1 mutation. We show that these est1- survivors arise as a result of the amplification and acquisition of subtelomeric elements (and their deletion derivatives) by a large number of telomeres. Hence, even when the primary pathway for telomere replication is defective, an alternative backup pathway can restore telomere function and keep the cell alive. PMID- 8477449 TI - Identification of the functional subunit of a dimeric transcription activator protein by use of oriented heterodimers. AB - We have constructed heterodimers consisting of two subunits: one CAP subunit that has a nonfunctional activating region but wild-type DNA binding specificity, and one CAP subunit that has a functional activating region but non-wild-type DNA binding specificity. We have oriented the heterodimers on lac promoter DNA by use of promoter derivatives that have DNA sites for CAP consisting of one wild-type half site and one non-wild-type half site, and we have analyzed the abilities of the oriented heterodimers to activate transcription. Our results indicate that transcription. Our results indicate that transcription activation requires the activating region of only one subunit of CAP: the promoter-proximal subunit. The oriented heterodimers method of this report should be generalizable to other dimeric transcription activator proteins. PMID- 8477450 TI - Functional analysis of a growth factor-responsive transcription factor complex. AB - Serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE) with an accessory factor, Elk-1. We constructed altered-binding specificity derivatives of SRF and Elk-1 that form a ternary complex at a mutated, inactive SRE; like Elk-1, the Elk-1 variant only binds its target as part of a ternary complex with SRF. Simultaneous expression of these SRF and Elk 1 derivatives restores serum-regulated activity to the mutated SRE in transfected cells. Efficient transcriptional activation is dependent on the regulated phosphorylation of Elk-1 C-terminal MAP kinase sites and requires the C-terminal sequences of SRF as well as SRF sequences that mediate ternary complex formation. These experiments provide direct evidence that SRF and Elk-1 functionally cooperate in the ternary complex at the SRE to regulate transcription. PMID- 8477451 TI - Mutations in U1 snRNA bypass the requirement for a cell type-specific RNA splicing factor. AB - Previous studies have demonstrated that efficient splicing of the primary transcript of the yeast MER2 gene requires the MER1 protein, which is produced only in meiotic cells. A genetic selection was devised to recover second-site mutations that bypass the requirement for MER1 in MER2 RNA-splicing. This selection identified a mutation in SNR19, the gene for U1 snRNA. The suppressor mutation affects the first residue in U1 snRNA, allowing this nucleotide to base pair with the eighth nucleotide in the MER2 intron. This base in MER2 lies outside the conserved hexanucleotide that defines the 5' splice site in yeast. The MER2 5' splice site (GUUCGU) differs from the consensus in yeast (GUAYGU) at the third position. When this nucleotide is mutated to restore the consensus, base pairing with U1 snRNA is increased and the requirement for MER1 is alleviated. PMID- 8477452 TI - Yeast extracellular proteases. AB - Many species of yeast secrete significant amounts of protease(s). In this article, results of numerous surveys of yeast extracellular protease production have been compiled and inconsistencies in the data and limitations of the methodology have been examined. Regulation, purification, characterization, and processing of yeast extracellular proteases are reviewed. Results obtained from the sequences of cloned genes, especially the Saccharomyces cerevisiae Bar protease, the Candida albicans acid protease, and the Yarrowia lipolytica alkaline protease, have been emphasized. Biotechnological applications and the medical relevance of yeast extracellular proteases are covered. Yeast extracellular proteases have potential in beer and wine stabilization, and they probably contribute to pathogenicity of Candida spp. Yeast extracellular protease genes also provide secretion and processing signals for yeast expression systems designed for secretion of heterologous proteins. Coverage of the secretion of foreign proteases such as prochymosin, urokinase, and tissue plasminogen activator by yeast in included. PMID- 8477453 TI - Zymomonas mobilis--science and industrial application. AB - Zymomonas mobilis is undoubtedly one of the most unique bacterium within the microbial world. Known since 1912 under the names Termobacterium mobilis, Pseudomonas linderi, and Zymomonas mobilis, reviews on its uniqueness have been published in 1977 and 1988. The bacterium Zymomonas mobilis not only exhibits an extraordinarily uniqueness in its biochemistry, but also in its growth behavior, energy production, and response to culture conditions, as well as cultivation techniques used. This uniqueness caused great interest in the scientific, biotechnological, and industrial worlds. Its ability to couple and uncouple energy production in favor of product formation, to respond to physical and chemical environment manipulation, as well as its restricted product formation, makes it an ideal microorganism for microbial process development. This review explores the advances made since 1987, together with new developments in the pure scientific and applied commercial areas. PMID- 8477454 TI - Phylogenetic analysis of the myosin superfamily. PMID- 8477455 TI - Flagellar radial spoke: a model molecular genetic system for studying organelle assembly. PMID- 8477456 TI - Primary and secondary chick heart fibroblasts: fast and slow-moving cells show no significant difference in microtubule dynamics. AB - Highly motile chick heart fibroblasts in primary culture (1 degree CHFs) gradually convert into much slower-moving secondary (2 degrees) cells. The polarized movement of the latter, but not the former, cell type has been found to be dependent on an intact microtubule (MT) network [Middleton et al., 1989, J. Cell Sci. 94:25-32]. To investigate the comparative stability of the MT networks of 1 degree s and 2 degrees s, turnover was investigated by microinjection of biotin-labeled brain tubulin to act as a reporter. MTs in both cell types were found to be very dynamic, with the MT networks effectively disassembled by about 30 min in 1 degree CHFs and 60 min in 2 degrees CHFs, with mainly MT fragments remaining beyond these times. All MTs and fragments were found to have turned over by 1 h in 1 degree CHFs and 80 min in 2 degrees s. Because 2 degrees CHFs were found to be on average six times larger than 1 degree s, the difference in MT turnover time was considered largely due to the size difference. For both 1 degree and 2 degrees cells, the more slowly turning over MTs were generally curly and perinuclear in distribution, resembling stable MTs in other systems, but they appeared significantly earlier in CHFs. However, no discrete subpopulations of slower turning over MTs were found to be associated with either the leading edges or the processes of either cell type. In addition, no major differences were identified in the patterns of modified alpha-tubulin along the MTs or of MT cold or drug stability. It is concluded that MTs do not have a direct structural or skeletal function in maintaining a polarized 2 degrees CHF cell shape, but rather play an ancillary role. PMID- 8477457 TI - Reactivation of demembranated, cytosol-free ram spermatozoa. AB - A procedure for preparing cytosol-free ram sperm models was developed. Sperm are introduced to a Triton X-100-containing demembranation medium layered on top of a discontinuous Percoll gradient. After brief exposure to the demembranating solution, the sperm are separated from the detergent-soluble components by centrifugation through a 55% Percoll layer, finally collecting on top of a 90% Percoll cushion from where they are recovered. Optimum conditions consisted of Triton X-100 at 0.20% and a demembranation time of 35 sec. Cross-sections of midpieces and principal pieces of the demembranated sperm were examined by electron microscopy. With 0.20% Triton X-100 in the demembranation medium, 86% of the cross-sections showed no plasma membranes and the rest had broken plasma membranes. The remaining tail structures appeared to be morphologically intact. Assay of phosphoglucose isomerase as a marker enzyme confirmed that at least 98% of the cytosolic protein was removed. Ram sperm models obtained by this procedure could be reactivated, and the percent motility and beat parameters were similar to those of the intact sperm. Reconstitution with the detergent-soluble components was neither required for, nor enhanced, reactivation. Therefore, demembranated ram sperm do not require a detergent-soluble protein factor for reactivation. PMID- 8477458 TI - Elastic properties of titin filaments demonstrated using a "freeze-break" technique. AB - A "freeze-break" technique (Trombitas, K.: Acta Biochim. Biophys. Hung. 6:419 427, 1971) and immunoelectron microscopy were used to study the elastic properties of titin filaments. Small bundles of freshly prepared rabbit psoas muscle fibers were quickly frozen and broken under liquid nitrogen to fracture sarcomeres in planes perpendicular to the filament axis, in each of various regions along the sarcomere. The still-frozen specimens were thawed during fixation to allow elastic filaments to retract. The broken specimens were then labelled with monoclonal anti-titin antibodies against an unique epitope in the I band. The titin epitopes were normally positioned symmetrically about the Z-line. However, in sarcomeres broken at the A-I junction, the epitopes no longer remained symmetrical: the titin filaments in the broken half-sarcomere retracted, independently of the thin filaments, forming a dense band just near the Z-line. The retracted density apparently did not reach the Z-line; retraction stopped at the level of the so-called N1-line. In sarcomeres broken at the Z-line level, the titin filaments retracted in the opposite direction. In this case the titin epitope retracted all the way to the ends of the thick filaments. It appears then that titin molecules form elastic filaments that are independent of thin filaments in most of the I-band. Near the Z-line, however, the titin filaments either have an inelastic domain or associate firmly with the thin filaments at the N1-line level. PMID- 8477459 TI - [New findings in chronic granulomatous disease]. AB - Chronic granulomatous disease is a rare hereditary disease characterized by repeated infections affecting in particular the skin, lymph nodes and internal organs. Histological examination in the affected tissues reveals a granulomatous inflammation. The aetiological agents of infection are most frequently staphylococci, G-bacteria, Candida and Aspergillus. From the immunological aspect it is an inborn immunodeficiency affecting professional phagocytes (monocytes and granulocytes) which are unable to kill some ingested microorganisms. The molecular basis of the defect is affection of the NADPH oxidase enzyme complex at various sites which explains the genetic heterogeneity of the disease. The condition is usually manifested in early childhood, it has a variable course; if untreated, the affected subjects frequently die in child age. By early diagnosis of the disease and suitable therapy the quality of life of the patients can be improved, serious complications can be prevented and the patients may reach adult age. The submitted paper is a review of contemporary knowledge of the disease, in particular its molecular basis and ensuing classification, as well as possible diagnosis and treatment of the disease. Several case-histories are presented. PMID- 8477460 TI - [Detection and reduction of mental and motor disorders in childhood. 2. Fundamentals and risks in longitudinal research in pediatrics]. AB - The study characterizes basic types of longitudinal research designs for the long term follow-up of children in health and disease. First the authors mention briefly the principles and disadvantages of cross-sectional research designs. Then they present a detailed account of methods of longitudinal research projects, evaluation of their advantages and their risks. Roughly fifty-year experience with longitudinal designs indicates that this pretentious research strategy can provide an overall view of developmental trends as regards changes of the health status of children in the ontogenetic perspective and contribute to improvement of health care of the child population. PMID- 8477461 TI - [Neurologic findings in mild mental retardation]. AB - The author subjected to neurological examination all children from a special school for retarded children (39 children, 22 boys, 17 girls). All children had a positive neurological finding. Central hypotonic syndrome was revealed most frequently--31 children; static tremor of the upper extremities--11 children and static tremor of the lower extremities--8 children. Minor cerebellar symptomatology was found in 10 children, developmental dyspraxia-dysgnosia in 6 children. Sixteen children were related (brother and sister, two sisters and cousins, etc.) PMID- 8477462 TI - [Rhythm disorders after acute viral myocarditis]. PMID- 8477463 TI - [Acute tubulointerstitial nephritis as a manifestation of furantoin poisoning]. PMID- 8477464 TI - [An unusual cause of respiratory failure. Bronchobiliary fistula]. AB - The authors describe the treatment of a patient with an inborn bronchobiliary fistula. The ex post finding that the fistula had two insertions in the bronchus called in the final stage for a combined thoraco-abdominal approach with resection of the right lower pulmonary lobe with ligature of the fistula beneath the diaphragm. Although inborn bronchobiliary fistulae are very rare, they must be considered in the differential diagnosis of causes of chronic respiratory distress syndrome in children. Early diagnosis and adequate surgical treatment make it possible to prevent serious chronic cardiorespiratory disease. PMID- 8477465 TI - [ACE inhibitors--a potential new group of drugs for treatment of kidney diseases]. AB - ACE inhibitors, which till recently were used almost exclusively for treatment of cardiovascular diseases, are becoming a perspective group of drugs also in the treatment of nephropathies. It was found that they are effective in particular in the treatment of proteinuria of varying origin and have also a marked renoprotective effect and are therefore recommended to retard progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard progression of chronic glomerulonephritis and diabetic nephropathy. We may expect already in the near future that their therapeutic application will be substantially extended also in clinical nephrology. PMID- 8477466 TI - [Surfactant in the therapy of idiopathic respiratory distress syndrome]. PMID- 8477467 TI - [An approach to the differential diagnosis of dilatation of the caliceal-pelvic system in children]. AB - The authors submit suggestions for the differential diagnostic procedure in dilatation of the calico-pelvic system in children involving consecutive application of non-invasive methods to methods pretentious for the patient. In the second part they present a review of recent findings regarding visualization techniques of the hollow renal system. PMID- 8477468 TI - [Cooperation between the pediatrician and orthopedist in the diagnosis of congenital hip dislocation]. AB - The author summarizes the principles of clinical diagnosis, referring to experience assembled in an investigation comprising more than 35,000 neonates during past years. The submitted pattern could be a practical instruction for examination of the hip joints by paediatricians--neonatologists. The author emphasizes the fact that the diagnosis of complete dislocation unless irreponible is very easy, and being a clinically very obvious defect, it should not be missed. In other countries the trend predominates to ensure examination of the hip joints of neonates by paediatricians-neonatologists for whom this examination is a matter of routine. The author outline possibilities of ultrasonographic examination, static as well as dynamic. In large towns it proved useful to establish an ultrasonographic examination room where some 4000 infants aged 2-3 weeks are examined. The hitherto used classification of ultrasonic examination is not quite reliable in view of "over-diagnosis" and thus to unnecessary therapy which can lead--as any abduction therapy--to complications such as avascular necrosis. Paediatricians-neonatologists should master the clinical problem and be aware of the responsibility for early clinical diagnosis to enable orthopaedists to specify indication for early treatment based on ultrasonographic examination. PMID- 8477469 TI - [Personal experience with the use of Rulid (roxithromycin) in children less than 1 year of age]. AB - The authors give an account of the use of Roxithromycin (preparation Rulide) in children of the youngest age group, i.e. in infants. From January 1989 to April 1992 they treated 24 children under 5 weeks to 12 months of age with Roxithromycin. Roxithromycin was administered in amounts from 5 to 10 mg/kg after 12-hour intervals in the course of 4 to 12 days. In 22 children a favourable clinical effect was observed, in two children antibiotic treatment had to be changes because there was no clinical response. Undesirable effects, i.e. vomiting, during Roxithromycin were observed only in two children. In no instance was it necessary to discontinue treatment. PMID- 8477470 TI - [HLA antigens in patients with celiac disease]. AB - In 104 non-related children with coeliac disease, all from northern Moravia, the authors assessed the distribution of HLA antigens class I and II and compared the findings with a control group. They revealed a positive association between HLA A1 (62% sick subjects as compared 27% healthy ones), B8 (68% as compared with 18%), DR3 (66% as compared with 14%) and DQw2 (79% as compared with 23%). In HLA antigens class II there is a higher relative risk of the disease for subjects with antigens DR3 and DQw2 and a higher aetiological fraction for the investigated antigens. PMID- 8477471 TI - [Epidemiology of childhood cerebral palsy in Slovakia]. AB - In the 5.3 million population of Slovakia the author investigated by means of questionnaire screening the prevalence and incidence of cerebral palsy in children. The questionnaires were processed in collaboration with child neurologists and district paediatricians from all 38 Slovak districts. The author revealed that in 1990 child neurologists recorded 6,214 1-14-year-old children with the diagnosis of cerebral palsy, i.e. the motor form. The prevalence of cerebral palsy in children in Slovakia is 4.9 and the incidence 9.0. The assembled data are valuable in the system of comprehensive care of children with cerebral palsy, for establishment of an early diagnosis and early rehabilitation treatment. PMID- 8477472 TI - [Immunologic findings in children with abnormal reactions after vaccination]. AB - In a group of 89 children with abnormal reactions after administration of the mixed vaccine against diphtheria, tetanus and whooping cough, after the mixed vaccine against diphtheria and tetanus, the live measles vaccine and oral poliovaccine, a detailed analysis was made of the case-history, and basic parameters of cellular and humoral immunity were examined. In these children the intensity of post-vaccination reactions was beyond the range of accepted criteria of mild and medium reactions or complications. In 17.3% of the children with an abnormal reaction after the mixed vaccine against diphtheria, tetanus and whooping cough a reduced IgA level was proved, while in the control group a reduced level was found only in 3.3%. 50% of the children who developed an abnormal reaction after the oral poliovaccine and the mixed vaccine against diphtheria, tetanus and whooping cough and at the same time some relative suffered from clinical signs of atopia, a reduced number of E rosettes of lymphocytes was recorded. 80% of the children who developed an abnormal reaction after the measles vaccine and some relative suffered from atopic disease, had low titres of specific antibodies against tetanic toxoid. Evidence was provided that children with certain precisely defined abnormal reactions after vaccination suffered significantly more frequently from reduced immune reactivity than children examined because of a suspected immunity defect. PMID- 8477473 TI - [Biostim in the treatment of recurrent respiratory diseases in children]. AB - The authors treated with Biostim (Roussel Uclaf Co., France) 20 children aged 3 to 15 years with relapsing and chronic diseases of the respiratory system. A favourable clinical effect was observed in 45% and improvement in 40% of the patients. In the investigated immunological indicators the response to treatment Biostim was manifested in the antibody immunity by a reduction of IgE values (P < 0.01) and of IgM (P < 0.05). As to cellular immunity, there was a significant increase of the phagocytic activity (P < 0.05). The tolerance of the preparation was very good. PMID- 8477474 TI - [Chronic cough in childhood--diagnosis and therapy]. PMID- 8477475 TI - [Neonatal sepsis--still a real problem]. AB - Neonatal sepsis is characterized by bacteraemia and clinical symptoms caused by microorganisms or their toxic products. The authors pay attention to epidemiological and predisposing factors, to the aetiology, pathogenesis, clinical signs and conditions for assessment of the diagnosis of neonatal sepsis as well as its therapy and prognosis. PMID- 8477476 TI - [Development of neonates at risk]. AB - From a group of 2542 children followed up for a prolonged period the authors selected several groups of risk neonates and compared their subsequent development with that of a control group from the same cohort. In the selected risk groups the authors evaluated anamnestic data of the mothers, somatic and neuropsychic development of the children. They compared also the psychomotor development of the children in the first years of life, their school attendance and progress, mean values of IQ and various mental deviations, as compared with children of the control group. By comparison with the incidence of analogous disorders the authors wanted to assess the ratic risks from early stages in later developmental disorders. PMID- 8477477 TI - [Familial incidence of the EMG syndrome]. PMID- 8477478 TI - [Incidence of rheumatic fever in Slovakia during the last 20 years]. AB - The incidence of rheumatic fever has a declining trend in Slovakia. In 1972 there were 26.7 primary attacks and 8.7 relapses per 100,000 children aged 0-14 years, in 1990 there are 0.5 primary attacks and 0.4 relapses and in 1991 0.4 primary attacks and no relapses. The interregional (former regions) distribution was to the disadvantage of eastern parts but gradually this was evened out. Rheumatic fever occurs in girls and boys, in the majority mild arthritis forms are involved with unequivocal regression of carditic-arthritic forms. The decline can be ascribed to the rising socio-economic standard and health care. PMID- 8477479 TI - [Detection and prevention of mental and motor disorders in childhood. 3. Synopsis of a longitudinal study]. AB - The submitted study is a brief account of theoretical and methodological solutions of a research project "Detection and reduction of sensory and motor disorders in childhood". In this research project the effectiveness of preventive examinations is assessed. It is focused on obtaining objective data on the incidence and prevalence of sensory and motor disorders. The authors describe the strategic aims, organization of data collection and processing. The empirical data should contribute to the rational development of preventive, therapeutic and rehabilitation procedures in paediatrics. PMID- 8477480 TI - [Air pollution and the occurrence of recurrent respiratory tract diseases in children during the first years of life]. AB - The authors investigate in a group of 211 children aged 2-6 years, incl. in particular a group of 33 2-year-old ones, in 1990 and checked in 1991 at two sites in Bratislava--a town with a varying concentration of NOX, SO2, dustiness and dust fallout--their influence on the incidence, type and course of relapsing respiratory disease. In both sites the concentrations of the mentioned noxious substances were beneath levels admitted by hygienists. In the place with higher concentrations, in particular of NOX, a significantly higher number of serious forms of relapsing respiratory diseases was recorded and an adverse course of the diseases in 2-6 year-old children and in particular in the 2-year-old ones. PMID- 8477481 TI - [Hylak Forte drops in the treatment of atopic eczema in children]. AB - The authors describe a group of 14 children with atopic eczema where to common Hismanal or Zaditen treatment in tablet form Hylak forte drops were added (L. Merckle Co.). After two months treatment the authors observed regression of subjective and objective complaints in 10 children. As to the investigated immunological parameters, they observed normal phagocyte activity of granulocytes and in the majority of children a decline of circulating immune complexes. This creates prerequisite conditions for reducing the costs of treatment and for starting aimed specific hyposensitization. PMID- 8477482 TI - [Therapeutic approach to the treatment of acute asthma in childhood]. AB - Acute deterioration of bronchial asthma with development of dyspnoea which involves the risk of failure of vital functions call for rapid and specialized therapeutic action which will prevent further deterioration of the condition and an as rapid as possible return of pulmonary functions to the range of normal values. In the treatment of acute asthma in the field as well as in in-patient departments different procedures are applied frequently based on tradition of the given department. In the submitted paper the author recapitulates recent views on the role of different procedures and the most frequently used drugs. The basis of modern therapy of acute asthma is above all inhalation treatment, high and frequent doses of beta 2-adrenergic preparations in particular during the initial stages of treatment and anti-inflammatory treatment with steroids. Theophyllines are considered drugs of second choice, the administration of infusions is also of limited importance. To ensure early treatment of acute asthma satisfactory and skilled cooperation of the patient and his closest surroundings is essential. Early therapeutic response to a deteriorating condition can substantially reduce the risk of development of serious conditions and reduce the need of hospital treatment. PMID- 8477483 TI - Sexually transmitted diseases in the age of AIDS. AB - Sexually transmitted diseases (STD) are common illnesses in the world. There is at least one new sexually transmitted disease consultation for every 100 persons a year in industrialised countries. Today the World Health Organisation estimates that there are 250 million new cases of STD every year world-wide, and over 20 distinct pathogens are currently recognised. While the overall incidence of STD have remained high in industrialised countries, the rates of increase of many bacterial STD such as syphilis and gonorrhoea were beginning to stabilise; but currently there is again a trend for these bacterial STD to rise in urban populations. PMID- 8477484 TI - Viral hepatitis complicating pregnancy--a five year hospital based retrospective study. AB - Limited data are available on viral hepatitis (VH) complicating pregnancy from Sri Lanka. We retrospectively studied all pregnant and non-pregnant women of child bearing age, who were admitted with VH to the Teaching Hospital Peradeniya between January 1987 and December 1991. During this period, there were 187 cases of icteric VH among non-pregnant women of child bearing age, but only 10 cases among pregnant women (hospital incidence of 0.35 cases of VH per 1000 pregnancy related admissions). Two of the 10 (case fatality 20%) pregnant women died of causes related to VH compared with only 3 of the 187 (1.6%) non-pregnant women (p < 0.001), giving a relative risk of death due to VH in pregnant women of 12.5 (95% confidence limits 1.8-85.6). The perinatal case fatality rate due to VH was 20%. VH complicating pregnancy does not appear to be a common cause of hospital admission, but pregnancy makes death due to VH more likely. VH complicating pregnancy also results in a high perinatal mortality. PMID- 8477485 TI - Knowledge about diabetes and metabolic control in diabetic patients. AB - It is widely accepted that patient education is an essential adjunct to the care of diabetic patients. A randomised controlled clinical trial in patient education was conducted at a diabetic and general medical clinic in Sri Jayawardenepura General Hospital. Two groups of diabetic patients matched for age, gender and duration of diabetes were allocated randomly to conventional care at general medical clinics or to a diabetes clinic where specific educational objectives were defined and patients trained to achieve these objectives. The doctors treating these patients were not 'blinded' to treatment groups. Diabetes knowledge was assessed using a diabetes knowledge scale and metabolic control assessed by mean fasting blood glucose. The patients attending the diabetic clinic showed significant improvement in both knowledge scores (67% vs 34%, p < 0.01) and mean fasting blood glucose 6.38 +/- 0.85 mmol/l vs 9.7 +/- 1.7 mmol/l, p < 0.01) at 6 months. We conclude that diabetes education improves patient knowledge and diabetes control. PMID- 8477487 TI - Does a teaspoonful measure 5 ml? PMID- 8477486 TI - Human infection with Dirofilaria (Nochtiella) repens in Sri Lanka. PMID- 8477488 TI - Health aspects of an urban elderly population. AB - The health status of an urban elderly Sinhala population ordinarily resident in their homes was investigated by interview and physical examination. Just over one fifth of the subjects had been hospitalised at least once for an episode of illness during the previous 12 months. 47.7% of the subjects complained of impaired vision, and 12.8% had cataract; 45.0% had less than the minimum number of teeth required for proper mastication; 24.8% of the subjects had impaired hearing. Medical histories showed that 10.1% of the subjects suffered from haemorrhoids; 2.0% were hemiplegic. A random single blood pressure recording showed 34.2% of the subjects to have a diastolic blood pressure of 95 mm Hg or more. 9.4% of the subjects had glucosuria. With the high morbidity seen among this elderly population a case is made for the establishment of geriatric clinics in government hospitals, and that care of the elderly be included in the Primary Health Care programme of Sri Lanka. PMID- 8477489 TI - Actinomycosis of the uterus. AB - A 59 year old woman with actinomycosis of the uterus is described. This is the first such case to be reported in Sri Lanka. PMID- 8477490 TI - Pseudocyst of the auricle. AB - Sixteen cases of pseudocyst of the auricle seen in Matara, Sri Lanka over a two year period are reported. These were managed with needle aspiration and contour pressure dressing for one week with almost 100% success. PMID- 8477491 TI - Chloramphenicol resistant typhoid fever. AB - We report a patient with typhoid fever caused by a strain of Salmonella typhi which was resistant to chloramphenicol. This is the first documentation of chloramphenicol resistant Salmonella typhi in Sri Lanka. PMID- 8477492 TI - General Hospital Colombo (4): Surgery. PMID- 8477493 TI - Changes in malaria vector prevalence in Sri Lanka: the need for local surveillance. PMID- 8477494 TI - Vitamin A toxicity. PMID- 8477495 TI - Screening for Turner syndrome. PMID- 8477496 TI - Blastocystis hominis: an old organism with a new significance. PMID- 8477497 TI - Spinal muscular atrophy, East and West. PMID- 8477498 TI - (2R), (1'R) and (2R), (1'S)-2-amino-3-(1,2-dicarboxyethylthio)propanoic acids from Amanita pantherina. Antagonists of N-methyl-D-aspartic acid (NMDA) receptors. AB - An antagonist of NMDA-sensitive glutamate receptors in rat brain membrane and rat spinal motoneurones was isolated from Amanita pantherina and identified as a diastereoisomeric mixture of 2-amino-3-(1,2-dicarboxyethylthio)propanoic acids. The mixture was separated and the absolute configurations of the components were determined as (2R), (1'R) and (2R), (1'S), by analysis of the optical properties. PMID- 8477499 TI - Palbinone, a novel terpenoid from Paeonia albiflora; potent inhibitory activity on 3 alpha-hydroxysteroid dehydrogenase. AB - Palbinone, a novel terpenoid isolated from the roots of Paeonia albiflora, showed a strong inhibitory activity on the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-linked 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) of rat liver cytosol. The structures of palbinone and a known compound, paeonilactone-B isolated from the active fraction of this plant were determined by the use of 2D NMR techniques (1H-1H COSY, 1H-13C COSY, 1H-13C long range COSY, and HMBC). PMID- 8477500 TI - Synthetic study on selenocystine-containing peptides. AB - N-9-Fluorenylmethoxycarbonyl-Se-4-methoxybenzylselenocysteine++ + [Fmoc-Sec(MBzl) OH] was synthesized from selenocystine and successfully applied to Fmoc-based solid-phase peptide synthesis. The stability and the deprotection conditions of the Se-MBzl group were examined. The diselenide bond of a peptide was directly and effectively established between Sec(MBzl) residues by treatment with iodine or the dimethyl sulfoxide-trifluoroacetic acid system. Reduction kinetics of diselenide and disulfide in model peptides by reduced glutathione were also studied comparatively. PMID- 8477501 TI - Agents for the treatment of overactive detrusor. IV. Synthesis and structure activity relationships of cyclic analogues of terodiline. AB - A series of pyrrolidine derivatives were synthesized and examined for inhibitory activity on detrusor contraction in vivo. Among those compounds, 5,5-dimethyl-2 (2,2-diphenylethyl)-3-isopropylidenepyrrolidine+ ++ hydrochloride (41.HCl), 2 (2,2-di(4-fluorophenyl)ethylene)-5,5-dimethyl-3-isopropylidenepyrro lidine hydrochloride (42.HCl), (+)-5,5-dimethyl-2-(N,N-diphenylaminomethyl)-3 isopropylidenepy rrolidine hydrochloride (+)-(43a.HCl), (-)-5,5-dimethyl-2-(N,N diphenylaminomethyl)-3-isopropylidenepy rrolidine hydrochloride (-)-(43a.HCl), and 2-(N,N-di(4-fluorophenyl)aminomethyl)-5,5-dimethyl-3-isopropylidenepy rrolidine methanesulfonate (43b.MsOH) showed stronger inhibitory activity on detrusor contraction than terodiline. PMID- 8477502 TI - Syntheses and inhibitory effects on gastric lesions of trans guanidinomethylcyclohexane carboxylic acid arylamides. AB - A novel series of trans-guanidinomethylcyclohexanecarboxylic acid (trans-GMCHA) arylamides was synthesized. The several trans-GMCHA arylamide derivatives showed more potent inhibitory effects on the stress- and HCl-ethanol-induced gastric ulcers than cetraxate in rats. In acute toxicity studies in mice, most amides showed such severe toxicity that all mice injected with these compounds (50 mg/kg, i.p.) died. However, mice injected with the trans-GMCHA (2'-,3'- and 4' ethoxycarboxy)phenylamide (7, 8 and 9) which bear an alkyloxycarbonyl group at benzene ring survived. From these results, trans-GMCHA (2' ethoxycarbonyl)phenylamide (7) was selected as a promising anti-ulcer agent. PMID- 8477503 TI - Amino acids and peptides. XVII. Synthesis of peptides related to N-terminal portion of fibrin alpha-chain and their inhibitory effect on fibrinogen/thrombin clotting. AB - Various peptides related to N-terminal portion of fibrin alpha-chain were synthesized by the solution method and the solid-phase method, and their inhibitory effect on fibrinogen/thrombin clotting was examined. Extension of peptide chain from N-terminal tripeptide decreased the inhibitory effect. The most potent effect was shown by N-terminal decapeptide analog, H-Gly-Pro-Arg-Pro Pro-Glu-Arg-His-Gln-Ser-NH2. PMID- 8477504 TI - Central cholinergic agents. IV. Synthesis and acetylcholinesterase inhibitory activities of omega-[N-ethyl-N-(phenylmethyl)amino]-1-phenyl-1-alkanones and their analogues with partial conformational restriction. AB - Inhibitors of acetylcholinesterase (AChE) have been designed based on a working hypothesis of the enzyme's active site. These compounds were tested for their inhibitory activities on AChE and omega-[N-ethyl-N-(phenylmethyl)amino]-1-phenyl 1-alkanones (3) were found to be potent inhibitors. Various analogues of 3 were prepared to study the effect on AChE inhibition of partial restriction of conformation. Compounds with potent AChE inhibition were further evaluated in terms of central selectivity: the ratio of central action (ameliorating effect on scopolamine-induced memory impairment using a T-maze alternation task) to peripheral action. PMID- 8477505 TI - Preparation of glycyrrhetic acid beta-glycosides having beta (1-->2)-linked disaccharides by the use of 2-O-trichloroacetyl-beta-D-pyranosyl chlorides and their cytoprotective effects on hepatic injury in vivo. AB - Stepwise glycosidation was adopted for the construction of glycyrrhetic acid beta glycosides (27-30) having beta (1-->2)-linked disaccharides such as 2-O-beta-D glucuronopyranosyl-beta-D-glucopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D galactopyranose, 2-O-beta-D-glucopyranosyl-beta-D-glucuronopyranose and 2-O-beta D-galactopyranosyl-beta-D-glucuronopyranose. In the first glycosidation, 2-O trichloroacetyl-beta-D-payranosyl chlorides (9-11) were utilized as starting sugar derivatives to react with methyl glycyrrhetinate (5): Glycosidation of 5 with 9 and 10 gave beta- and alpha-monoglycosides (12) and (13), and (15) and (16), respectively. Treatment of the beta-glycosides 12 and 15 with ammonia saturated ether gave products (14) and (17), respectively. The glycosidation of 5 with 11 followed by treatment with ammonia-saturated ether gave compounds (18) and (19), respectively. The second step glycosidations of 14 and 17 with methyl 2,3,4-tri-O-acetyl-alpha-D-glucuronatopyranosyl bromide (20) gave diglycoside derivatives (23) and (24), respectively, and that of 18 with 2,3,4,6-tetra-O acetyl-alpha-D-glucopyranosyl bromide (21) and -alpha-D-galactopyranosyl bromide (22) gave diglycoside derivatives (25) and (26), respectively. The removal of the protecting groups of 23-26 gave diglycosides 27-30, respectively, having a beta-D glucuronopyranose (beta-D-glcUA) as one of two sugar components in the molecules. The cytoprotective effects of the synthesized glycosides 27-30 on carbon tetrachloride (CCl4)-induced hepatotoxicity in vivo were compared with diglycosides 31-33 having only neutral sugar components and naturally occurring glycyrrhizin (34) having two acidic sugar components (beta-D-glcUA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477506 TI - Direct injection analysis of atenolol enantiomers in plasma using an achiral/chiral coupled column HPLC system. AB - A novel HPLC system was developed with an achiral/chiral coupled column for the direct injection analysis of atenolol (AT) enantiomers in plasma. The system consists of a size-exclusion column, an ODS silica column and a newly developed beta-cyclodextrin perphenylcarbamate(ph-beta-CD)-bonded silica column connected in a series via two switching valves. The neat plasma sample was directly injected onto the size-exclusion column, and the deproteinized fraction of AT enantiomers was concentrated on the ODS silica column. The enantiomers were then transferred and separated mutually on the ph-beta-CD silica column. The calibration line for each of the AT enantiomers was linear in the range of plasma concentration of 10-200 ng/ml (r > 0.9997) with good reproducibility (CV < 9.7%, n = 20). The recoveries from plasma were almost complete (> 97.4%) for both enantiomers. One analysis finished within 30 min. The developed system was applied to the enantioselective determination of plasma concentration-time curve of AT after the oral administration of racemic AT to a healthy volunteer. PMID- 8477507 TI - The first specific antibody against cytotoxic polyacetylenic alcohol, panaxynol. AB - Antitumor polyacetylenic alcohol, panaxynol, was isolated and purified from a powder of the root of Panax ginseng C.A. Meyer. Panaxynol inhibited the growth of various kinds of cultured tumor cell lines in a dose-dependent manner. In this paper we demonstrated the first specific antibody production against panaxynol. Anti-panaxynol antibody was elicited in rabbits by immunization with panaxynol hemisuccinate-bovine serum albumin conjugate (panaxynol hemisuccinate-BSA conjugate). An enzyme immunoassay (EIA) for the determination of panaxynol was established using a double-antibody technique. The EIA was highly specific against panaxynol although the antibody showed a minimal cross-reactivity with other types of polyacetylenic alcohol, i.e. panaxydol (12.0%) and panaxytriol (0.77%). Panaxynol at a concentration as low as 6.4 ng/ml can be detected. Using this assay we reconfirmed the rapid consumption of panaxynol by target tumor cells in an in vitro-culture system. The anti-panaxynol antibody may be a valuable tool for studies of the biological properties of polyacetylenic compounds. PMID- 8477508 TI - Triterpene glycosides from the bark of Robinia pseudo-acacia L. II. AB - From the bark of Robinia pseudo-acacia L., six new triterpene glycosides, Robiniosides E--J, were isolated and their structures were elucidated as abrisapogenol B 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2) beta-D - glucuronopyranoside (1), abrisapogenol B 3-O-alpha-L-rhamnopyranosyl(1- >2)-beta-D- glucopyranosyl(1-->2)-beta-D-glucuronopyranoside (2), 3-O-alpha-L rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D - glucuronopyranosyl abrisapogenol B 22-O-alpha-L-rhamnopyranoside (3), 3-O-alpha-L-rhamnopyranosyl(1- >2)-beta-D- glucopyranosyl(1-->2)-beta-D-glucuronopyranosyl abrisapogenol B 22-O alpha-L-rhamnopyranoside (4), 3-O-alpha-L- rhamnopyranosyl(1-->2)-beta-D galactopyranosyl(1-->2)-beta-D-glucuron opyranosyl abrisapogenol E 30-O-beta-D apiofuranosyl(1-->6)-beta-D-glucopyranoside (5) and 3-O-alpha-L-rhamnopyranosyl(1 ->2)-beta-D-glucopyranosyl(1-->2)-beta-D- glucuronopyranosyl abrisapogenol E 30-O beta-D-apiofuranosyl(1-->6)-beta-D-glucopyranoside (6), respectively. PMID- 8477509 TI - Two new steroidal saponins from dried fermented residues of leaf-juices of Agave sisalana forma Dong No. 1. AB - In a previous paper, we reported the isolation and structure determination of three new steroidal saponins, dongnosides C (3), D (2) and E (1) from the dried fermented residues of leaf-juices of Agave sisalana forma Dong No. 1. In a continuing study on this plant, two additional new major steroidal saponins, named dongnosides B (4) and A (5), were obtained. Their structures were characterized respectively as tigogenin 3-O-alpha-L-rhamonpyranosyl-(1-->4)-beta D-glucopyranosyl-(1-->2)- [beta-D- glucopyranosyl-(1-->3)]-beta-D-glucopyranosyl (1-->4)-beta-D-galactop yranoside and 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D glucopyranosyl-(1-->2)-[beta- D- xylopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1- >3)]-beta-D- glucopyranosyl-(1-->4)-beta-D-galactopyranoside on the basis of chemical and physicochemical evidence. PMID- 8477510 TI - Naturally occurring 5-lipoxygenase inhibitor. II. Structures and syntheses of ardisianones A and B, and maesanin, alkenyl-1,4-benzoquinones from the rhizome of Ardisia japonica. AB - New alkenyl-1,4-benzoquinones, ardisianones A (1) and B (2), and the known maesanin (3) as 5-lipoxygenase inhibitors have been isolated from the rhizome of Ardisia japonica. Their structures have been elucidated as 2-methoxy-6-[(Z)-10' pentadecenyl]-1,4-benzoquinone and 5-hydroxy-2-methoxy-6-[(Z)-8'-tridecenyl]-1,4 benzoquinone, respectively, on the basis of spectroscopic data and chemical degradation. Ardisianone A (1), maesanin (3) and belamcandol A (7) have been synthesized starting from belamcandol B (6), readily prepared by Wittig reaction between 9-(2-tetrahydropyranyloxy)nonanal and 3,5 dimethoxybenzyltriphenylphsophonium bromide followed by selective demethylation with sodium thioethoxide. PMID- 8477511 TI - Comparative studies on the constituents of ophiopogonis tuber and its congeners. VIII. Studies on the glycosides of the subterranean part of Ophiopogon japonicus Ker-Gawler cv. Nanus. AB - Two monoterpene glycosides, tentatively named OJV-I (1) and OJV-II (2), and eight steroidal glycosides, tentatively named OJV-III (3), OJV-IV (4), OJV-V (5), OJV VI (6), OJV-VII (7), OJV-VIII (8), OJV-IX (9) and OJV-X (10), were isolated from the butanol-soluble fraction of the fresh subterranean part of Ophiopogon japonicus KER-GAWLER cv. Nanus. Among these compounds, 1, 2, 3, 4, 5, 6 and 7 were identified as l-borneo1 O-beta-D-glucopyranoside, l-borneo1 O-beta-D apiofuranosyl (1-->6)-beta-D-glucopyranoside, ophiopogonin B, glycoside C, ophiopogonin D, Ls-10, and ruscogenin 1-O-sulfate, respectively. The structures of compounds 8, 9, and 10 were established to be (23S,24S,25S)-23,24 dihydroxyruscogenin 1-O-[ alpha-L-rhamnopyranosyl(1-->2)] [beta-D-xylopyranosyl(1 ->3)]-alpha-L-arabinopyranoside 24-O-beta-D-fucopyranoside, (23S,24S,25S)-23,24 dihydroxyruscogenin I-O-[alpha-L-2,3,4-tri-O-acetylrhamnopyranosyl(1-->2)][beta-D xylo pyranosyl(1-->3)]-alpha-L-arabinopyranoside 24-O-beta-D-fucopyranoside, and (23S,24S,25S)-23,24-dihydroxyruscogenin 1-O-[alpha-L-2,3,4-tri-O acetylrhamnopyranosyl(1-->2)] [beta-D-xylopyranosyl(1-->3)]=alpha-L arabinopyranoside 24-O-beta-D-fucopyranoside, respectively. PMID- 8477512 TI - Development of a model membrane system using stratum corneum lipids for estimation of drug skin permeability. AB - Several model membrane systems have been reported to predict the skin permeability of drugs, but model membranes using stratum corneum (SC) lipids have never been reported. Thus, we developed a model membrane system for drug permeation study by fixing liposomes composed of SC lipids (ceramides, palmitic acid, cholesterol, and cholesterol-3-sulfate) onto a supporting filter, Biodyne B. The permeability of several drugs with different lipophilicities was investigated. Permeability increased with drug lipophilicity, estimated from the octanol/buffer solubility ratio of the drug. For relatively polar drugs, however, the permeability was almost constant, and very close to the value of a K+ ion, suggesting the membrane has both lipidic and aqueous pathways. Drug permeability through our system was compared with that through guinea pig skin. A good correlation (r = 0.880) was observed, although the former was one order of magnitude greater than the latter. Our model system will be useful not only for practical application, but also for basic studies, such as the elucidation of the relationships between SC lipid composition and drug permeability. PMID- 8477513 TI - Blood clearance and tissue distribution of various formulations of alpha tocopherol injection after intravenous administration. AB - The in vivo elimination and tissue distribution (2 h after administration) of various types of formulations of alpha-tocopherol as a model drug were examined in rats. An organic cosolvents formulation of alpha-tocopherol (alpha tocopherol/EtOH/polyethylene glycol 400) was rapidly removed from the blood circulation, the ratio of the distributed alpha-tocopherol was 20% in the lungs, about 70% in the liver and about 10% in the spleen. The main reason for this was considered to be the appearance of droplets more than 10 microns in diameter in the blood. Elimination of the micelle formulation using Brij58 from the blood was the most rapid, followed by Tween80 and HCO60. This order is thought to be due to the difference in the polyoxyethylene group among these surfactants. In liposome formulations, liposomes having a diameter of about 80 nm were the most stable in the blood circulation, and alpha-tocopherol was distributed in the reticuloendothelial system (RES) in the smallest ratio. The uptake of liposomes by the spleen and lungs depended on the liposome size. The uptake by the liver was in the decreasing order of 28 nm >> 42 nm, 151 nm, 195 nm, 3656 nm > 106 nm > 75 nm. The 100 nm lipid emulsion was eliminated from the blood more rapidly than the 100 nm liposome formulation. PMID- 8477514 TI - Microbial hydroxylation of (-)-eburnamonine by Mucor circinelloides and Streptomyces violens. AB - (6R)-6-Hydroxy-, (6S)-6-hydroxy- and (18S)-18-hydroxyeburnamonines were obtained by microbial conversion of (-)-eburnamonine using Mucor circinelloides and Streptomyces violens. Their structures were determined by analyses of the mass, 1H- and 13C-NMR spectra. (-)-Eburnamonine and the three hydroxylated compounds showed cerebral protecting effects against potassium cyanide intoxication in mice. PMID- 8477515 TI - Structure-activity relationship of lipopeptide from outer membrane of Escherichia coli and synthesis of highly immunopotenting lipopeptide derivatives with an achiral lipo-part. PMID- 8477516 TI - Natural course of endothelium-dependent and -independent responses in autogenous femoral veins grafted into the arterial circulation of the dog. AB - We examined the natural course of endothelium-dependent and -independent responses in reversed autogenous vein grafts during regeneration and tissue repair processes after vein grafting in dogs. Vein grafts implanted in the canine femoral artery were removed, cut into rings, and suspended in organ chambers for isometric tension recording at 3 days and 1, 2, 4, and 6 weeks after implantation. Endothelial cells were denuded from some rings. Control veins were taken from nonsurgically treated femoral veins. Acetylcholine caused endothelium dependent relaxations in the control veins, whereas in the vein grafts there was no evidence of endothelium-dependent relaxations to acetylcholine 3 days after the operation. Acetylcholine caused endothelium-independent contractions throughout the study. The endothelium-dependent responses to ADP and calcium ionophore A23187 were constantly maintained. Three days after the operation, the amplitude of norepinephrine-induced contractions of the vein grafts was impaired, and at 1 week the amplitude was recovered, although it was significantly smaller than the amplitude of contractions of the control veins at any postoperative period. Endothelium-independent relaxations to sodium nitroprusside were maintained throughout the study. Thus, there was a selective loss of acetylcholine-mediated relaxation in vein grafts in the early postoperative stage, a time when the intima is not thickened. These altered responses in vein grafts in the early postoperative period may have a role in graft failure. PMID- 8477517 TI - Selective contribution of two types of carotid sinus baroreceptors to the control of blood pressure. AB - This study was performed to determine if selective elimination of afferent input from two different types of previously described baroreceptors altered the ability of the dog to regulate blood pressure (BP), examining specifically if there was differential loss of baroreceptor control of tonic levels of baseline pressure versus dynamic changes in pressure. In the first series of experiments in this study, anodal block of the carotid sinus nerve was used to selectively block afferent input in a sequence from large-diameter A-fiber carotid baroreceptors (mostly type I) to smaller A-fiber and nonmyelinated C-fiber baroreceptors (mostly type II). In the second series of experiments, anesthetic block of the carotid sinus nerve with bupivacaine was used to selectively eliminate afferent input in reverse order from anodal block, first blocking input from baroreceptors with small afferent fibers and then additionally eliminating input from the larger-diameter A-fiber baroreceptors. The effects of selective elimination of each baroreceptor type were determined by monitoring baseline BP during constant carotid sinus pressure (CSP) perfusion of a vascularly isolated carotid sinus (tonic control) and obtaining baroreflex sensitivity (slope) during ramp pressure stimulations of the carotid sinus (dynamic control) under various blocking conditions. Low levels of anodal block significantly attenuated baroreflex sensitivity (-0.84 +/- 0.11 versus -0.63 +/- 0.10 mm Hg BP/mm Hg CSP) at levels of block that had no effect on tonic baseline BP (158.41 +/- 9.5 versus 160.7 +/- 9.5 mm Hg BP). In contrast, low levels of bupivacaine block produced significant increases in tonic BP (158.8 +/- 6.4 versus 169.0 +/- 6.5 mm Hg BP), whereas there was no effect on dynamic baroreflex sensitivity (-0.85 +/- 0.08 versus -0.73 +/- 0.08 mm Hg BP/mm Hg CSP). Thus, blocking large A-fiber baroreceptors resulted in significant decreases in baroreflex sensitivity without changes in baseline levels of BP, indicating primarily an attenuation in dynamic baroreflex regulation. Blocking of smaller A-fiber and unmyelinated C-fiber baroreceptors resulted in smaller decreases in baroreflex sensitivity and significant elevations in baseline BP, indicating a loss of tonic control of pressure. These results suggest that the two types of baroreceptors contribute differently to the regulation of blood pressure. PMID- 8477518 TI - Endothelium-dependent contractions in rabbit pulmonary artery are mediated by thromboxane A2. AB - This study was designed to characterize the endothelium-dependent contracting factor (EDCF) released by arachidonic acid (AA) and methacholine (MeCH) in the rabbit pulmonary artery. AA and MeCH contract the rabbit pulmonary artery; however, the effects of both are blocked by denuding the vessels and by administration of indomethacin (a cyclooxygenase inhibitor), dazoxiben (a thromboxane [TX] synthase inhibitor), and SQ29548 (a TXA2/prostaglandin [PG] H2 receptor antagonist). When segments of rabbit pulmonary artery were incubated with [14C]AA and the [14C] metabolites were resolved by reverse-phase high performance liquid chromatography (HPLC), radioactive products were observed that comigrated with 6-keto-PGF1 alpha and TXB2, the stable metabolites of prostacyclin and TXA2. The TXB2 radioactive peak was rechromatographed on normal phase HPLC and again migrated with TXB2. Finally, the structures of derivatized [14C]6-keto-PGF1 alpha and [14C]TXB2 peaks were confirmed by gas chromatography/mass spectrometry. The synthesis of [14C]6-keto-PGF1 alpha and [14C]TXB2 was inhibited by removal of the endothelium and by indomethacin. Dazoxiben inhibited the synthesis of [14C]TXB2 but not [14C]6-keto-PGF1 alpha. Using specific radioimmunoassays, AA and MeCH stimulated 6-keto-PGF1 alpha and TXB2 release. Indomethacin blocked the production of both 6-keto-PGF1 alpha and TXB2, whereas dazoxiben only blocked TXB2. In a superfusion/bioassay system, AA stimulated an endothelium-intact donor vessel to release a labile substance that contracted an indomethacin-treated endothelium-denuded recipient vessel. The EDCF released by AA had an approximate half-life of 30 seconds. Cultured rabbit pulmonary arterial endothelial cells synthesized 6-keto-PGF1 alpha but not TXB2. Immunohistochemical studies indicated the presence of cyclooxygenase, but not TX synthase, in pulmonary artery endothelial cells. TXA2 appears to be the EDCF released by AA and MeCH in rabbit pulmonary artery; however, TXA2 is not produced by endothelial cells but may arise from cells that adhere to the luminal surfaces, such as platelets or macrophages. PMID- 8477519 TI - Cardiac endothelial cells modulate contractility of rat heart in response to oxygen tension and coronary flow. AB - The aim of this study was to determine if endothelial cells in the heart release substances into the coronary perfusion medium that modify the contractility of myocardial cells. To assay the effects on the contractility of cardiac muscle of fluid that has passed through the coronary vasculature, a new method has been developed based on the cascade principle used to study vascular smooth muscle function. The coronary venous effluent from an isolated perfused working heart was collected periodically, and after reoxygenation it was used as the bathing medium for trabeculae isolated from the endocardial surface of another heart. The coronary venous effluent changed the contraction of the isolated trabeculae. The amplitude and the direction of the change depended on the degree of oxygen saturation of the coronary effluent before it was reoxygenated and the rate of coronary flow at the time the effluent was collected. The response of the trabecula to the coronary effluent was substantially altered by damaging the endocardial endothelium with a 1-second exposure to 0.5% Triton X-100 in Krebs' solution. It was completely eliminated by damaging endothelial cells in both the perfused heart producing the effluent and the trabecula on which the effluent was assayed. Therefore, endothelial cells are required for the presence of cardioactive substances in the coronary effluent. The production of a labile endothelium-derived upregulating (positively inotropic) factor and a more stable endothelium-derived downregulating (negatively inotropic) factor has been demonstrated and appears to account for all of the changes in myocardial contractility produced by the coronary effluent. Neither of the endothelium derived substances demonstrated in the isolated perfused heart is nitric oxide or endothelin. The concentration of the endothelium-derived upregulating factor is sensitive to oxygen tension, whereas the concentration of the endothelium-derived downregulating factor is sensitive to the rate of coronary flow but not oxygen tension. The coronary effluent appears to contain substances that stimulate secretion by the endothelial cells (preendothelial factors) as well as substances that have been produced by the endothelial cells (endothelial factors). The results indicate that during the passage of perfusion medium through the coronary vasculature upregulating and downregulating factors are added to the perfusate in relative concentrations that depend at least in part on local tissue PO2 and the rate of coronary flow. In the intact heart, this mechanism could operate to maintain balance between energy supply and work performed. PMID- 8477520 TI - Endocardial versus epicardial differences of intracellular free calcium under normal and ischemic conditions in perfused rat hearts. AB - Transmural heterogeneity of myocardial metabolism and function are present in the left ventricle under normal and ischemic conditions. To determine if endocardial versus epicardial differences of [Ca2+]i are also present, perfused rat heart studies using indo-1 fluorescence as an index of [Ca2+]i were performed in the left ventricular epicardium and endocardium. Hearts were studied during control conditions and low-flow ischemia. Results demonstrated the following: 1) At a pacing rate of 1.5 Hz, endocardial levels of diastolic and systolic [Ca2+]i (470 +/- 40 and 1,240 +/- 170 nM) were higher than epicardial levels (290 +/- 30 and 920 +/- 150 nM). 2) At a more physiological pacing rate of 5 Hz, endocardial levels of diastolic and systolic [Ca2+]i (680 +/- 50 and 1,230 +/- 70 nM) were also higher than epicardial levels (390 +/- 20 and 950 +/- 60 nM. 3) During low flow ischemia, endocardial levels of diastolic [Ca2+]i rose to a greater degree (from 680 +/- 50 to 1,050 +/- 70 nM at 10% of control coronary flow) compared with epicardial levels (from 390 +/- 20 to 580 +/- 40 nM at 10% of control flow), suggesting that the endocardium is more susceptible to low-flow ischemia. 4) The amplitude of the [Ca2+]i transient was the same at the endocardium (540 +/- 50 nM) and epicardium (560 +/- 50 nM) and did not change during low-flow ischemia, despite marked contractile dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477521 TI - Comparison of hirudin and heparin as adjuncts to streptokinase thrombolysis in a canine model of coronary thrombosis. AB - Recombinant desulfatohirudin (HI), a potent and specific thrombin inhibitor, was compared with heparin (HE) as an adjunct to streptokinase thrombolysis. In pentobarbital-anesthetized dogs, an occlusive thrombus (whole blood+thrombin) was introduced into the left anterior descending coronary artery (LAD) with superimposed endothelial damage and distal high-grade stenosis. Intravenous infusion of saline (vehicle), HI (0.3 mg/kg followed by 0.3 mg/kg per hour, 1 mg/kg followed by 1 mg/kg per hour, or 2 mg/kg followed by 2 mg/kg per hour), or HE (60 units/kg followed by 40 units/kg per hour or 100 units/kg followed by 60 units/kg per hour) was initiated 15 minutes before streptokinase (750,000 units for 60 minutes) administration. Vessel patency was monitored for 180 minutes after streptokinase administration with a volume flow probe on the proximal LAD. In dogs treated with no adjunctive agent (saline control), none of the vessels were recanalized with streptokinase. Both HI and HE promoted reperfusion, inhibited reocclusion, and reduced the residual thrombus mass in a dose-dependent fashion. However, at comparable levels of therapeutic anticoagulation (activated partial thromboplastin time [APTT] = 1.5-2.0 times baseline) HI exhibited a higher incidence of reperfusion (eight of eight dogs [100%] versus one of eight dogs [12%]), a shorter time to reperfusion (33 +/- 6 versus 59 minutes), a longer duration of initial reperfusion (106 +/- 21 versus 10 minutes), and a smaller residual thrombus mass than did HE. Likewise, the slope of the relation between the APTT prolongation and the total reperfusion time ("anticoagulation/antithrombosis profile") was almost five times higher for the combined HI data than for the HE data. Our results indicate that HI is more effective than HE in enhancing and sustaining coronary recanalization with streptokinase at a HI dose that modestly prolongs coagulation time and does not alter bleeding times. PMID- 8477522 TI - High density lipoprotein reverses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation. AB - We have recently reported that oxidized low density lipoprotein (ox-LDL) inhibits endothelium-dependent arterial relaxation through its increased lysophosphatidylcholine (LPC). In this study we examined whether high density lipoprotein (HDL) has any effect on the inhibition of endothelium-dependent relaxation by ox-LDL in isolated strips of rabbit thoracic aorta. Both low density lipoprotein (LDL) and HDL were isolated from normal human plasma, and LDL was oxidized by exposure to copper. Preincubation of arterial strips with ox-LDL (0.1-0.5 mg protein/ml) inhibited endothelium-dependent relaxation to acetylcholine (ACh) in a concentration-dependent manner. HDL (1 mg protein/ml) by itself had no effect on the relaxation to ACh. In the presence of HDL, the inhibition by ox-LDL was markedly reduced. Although synthetic L-alpha-palmitoyl LPC (5 micrograms/ml) completely abolished a relaxation to ACh, the preincubation of arterial strips with HDL completely prevented the LPC-induced inhibition. Moreover, a relaxation to ACh was almost completely recovered when the strips were washed with buffer containing HDL even after LPC-induced inhibition had occurred. HDL markedly reduced the incorporation of [1-14C]palmitate-labeled LPC ([14C]LPC) into cultured bovine aortic endothelial cells and promoted the release of cell-incorporated [14C]LPC into the medium, resulting in a reduction of the remaining [14C]LPC in the cells. Agarose electrophoresis after incubation of a mixture of ox-LDL labeled with [14C]LPC and unlabeled HDL demonstrated a transfer of [14C]LPC from ox-LDL to HDL. These results indicate that HDL reverses the ox LDL-induced impairment of endothelium-dependent relaxation by removing LPC from ox-LDL and preventing LPC from acting on the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477523 TI - Effects of chronic mitral regurgitation on diastolic function in isolated cardiocytes. AB - We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477524 TI - In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors. AB - Replication-deficient recombinant adenovirus vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in the endothelium. To evaluate the feasibility of adenovirus-mediated gene transfer in vivo in normal intact blood vessels, adenovirus vectors containing the Escherichia coli lacZ gene or a human alpha 1 antitrypsin (alpha 1AT) cDNA were injected in vivo into the lumen of an occluded vessel segment of sheep jugular vein and/or carotid artery. After 15 minutes of incubation, circulation was restored; the vessels were harvested 1-28 days later and evaluated for gene transfer and expression. Three days after in vivo exposure to the lacZ adenovirus vector, the endothelium of jugular veins and carotid arteries expressed beta-galactosidase. Exposure of jugular veins and carotid arteries in vivo to the alpha 1AT adenovirus vector resulted in the expression of alpha 1AT mRNA transcripts detected by Northern analysis and in the synthesis and secretion of alpha 1AT detected by ex vivo [35S]methionine labeling. Expression with the adenovirus vectors was efficient and easily detectable 1-14 days after injection, with maximum expression at 7 days. Expression was no longer evident at 28 days. Thus, adenovirus vectors are capable of transferring exogenous genes to the endothelium of normal arteries and veins with expression for at least 2 weeks, suggesting that these vectors have the potential for a variety of cardiovascular experimental and clinical applications. PMID- 8477525 TI - Muscle-specific gene expression. A comparison of cardiac and skeletal muscle transcription strategies. PMID- 8477526 TI - Troponin I gene expression during human cardiac development and in end-stage heart failure. AB - Recent reports have demonstrated the presence of two isoforms of troponin I in the human fetal heart, namely, cardiac troponin I and slow skeletal muscle troponin I. Structural and physiological considerations indicate that these isoforms would confer differing contractile properties on the myocardium, particularly on the phosphorylation-mediated regulation of contractility by adrenergic agonists. We have investigated the developmental expression of these isoforms in the human heart from 9 weeks of gestation to 9 months of postnatal life, using Western blots revealed with troponin I antibodies to detect troponin protein isoforms and Northern blots to detect the corresponding mRNAs. The results show the following: 1) Slow skeletal muscle troponin I is the predominant isoform throughout fetal life. 2) After birth, the slow skeletal isoform is lost, with cardiac troponin I being the only isoform detectable by 9 months of postnatal development. 3) The protein isoforms and their corresponding mRNAs follow the same pattern of accumulation, suggesting that the transition in troponin expression is regulated at the level of gene transcription. The developmental transition in troponin I isoform content has implications for contractility of the fetal and postnatal myocardium. We further analyzed right and left ventricular muscle samples from 17 hearts in end-stage heart failure resulting from pulmonary hypertension, ischemic heart disease, or dilated cardiomyopathy. Cardiac troponin I mRNA remained abundant in each case, and slow skeletal muscle troponin I mRNA was not detectable in any of sample. We conclude that alterations in troponin I isoform content do not therefore contribute to the altered contractile characteristics of the adult failing ventricle. PMID- 8477527 TI - In vivo observation of subendocardial microvessels of the beating porcine heart using a needle-probe videomicroscope with a CCD camera. AB - We developed a portable needle-probe videomicroscope with a charge-coupled device (CCD) camera to visualize the subendocardial microcirculation. In 12 open-chest anesthetized pigs, the sheathed needle probe with a doughnut-shaped balloon and a microtube for flushing away the intervening blood was introduced into the left ventricle through an incision in the left atrial appendage via the mitral valve. Images of the subendocardial microcirculation of the beating heart magnified by 200 or 400 on a 15-in. monitor were obtained. The phasic diameter change in subendocardial arterioles during cardiac cycle was from 114 +/- 46 microns (mean +/- SD) in end diastole to 84 +/- 26 microns in end systole (p < 0.001, n = 13, ratio of change = 24%) and that in venules from 134 +/- 60 microns to 109 +/- 45 microns (p < 0.001, n = 15, ratio of change = 17%). In contrast, the diameter of subepicardial arterioles was almost unchanged (2% decrease, n = 5, p < 0.01), and the venular diameter increased by 19% (n = 8, p < 0.001) from end diastole to end systole. Partial kinking and/or pinching of vessels was observed in some segments of subendocardial arterioles and venules. The percentage of systolic decrease in the diameter from diastole in the larger (> 100 microns) subendocardial arterioles and venules was greater than smaller (50-100 microns) vessels (both p < 0.05). In conclusion, using a newly developed microscope system, we were able to observe the subendocardial vessels in diastole and systole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477528 TI - Increased capillary permeability to albumin in diabetic rat myocardium. AB - To clarify the mechanism for the well-known increase in microvascular permeability that occurs with diabetes mellitus, we investigated capillary permeability to albumin in diabetic rat myocardium by electron microscopy using albumin-gold (Alb-Au) complexes as a tracer. Diabetes was induced by an intravenous injection of streptozotocin. After 24-32 weeks, hearts from diabetic rats and age-matched control rats were perfused with Krebs-Henseleit bicarbonate buffer containing Alb-Au for 5 or 20 minutes and then fixed and processed for electron microscopy. The binding and transport of Alb-Au by capillary endothelium was quantitatively evaluated. In control rats, Alb-Au particles were found preferentially bound to the luminal plasmalemmal vesicles. In diabetic rats, the labeling of luminal vesicles was more extensive and more pronounced after 5 minutes of perfusion when compared with control vesicles. The plasma membrane proper was also heavily labeled in diabetic rats. After 20 minutes, Alb-Au particles were transported across the capillary endothelium via plasmalemmal vesicles, but they did not penetrate the intercellular junctions in either control or diabetic rats. The vesicular transport of Alb-Au across the capillary endothelium was significantly increased in the diabetic myocardium when compared with control myocardium (percentage of abluminal labeled vesicles, 25.9 +/- 5.5% versus 1.3 +/- 0.5%; p < 0.01). The study on food-restricted rats with body weights close to those of diabetic rats suggested that caloric deficiency alone did not have much effect on capillary permeability. The data indicate that capillary permeability to albumin is markedly increased in diabetic myocardium because of enhanced vesicular transport. This may play an important role in the pathogenesis of diabetic cardiomyopathy. PMID- 8477529 TI - Identification of functional PGH2/TxA2 receptors on human endothelial cells. AB - Although functional receptors for thromboxane A2 and prostaglandin H2 (TxA2/PGH2) have been identified in platelets and vascular smooth muscle cells, receptor mediated events in human endothelial cells stimulated by these endoperoxides have not been shown. Using cultured endothelial cells harvested from human umbilical or saphenous veins, we measured the effect of the TxA2 mimetic U46619 on mobilization of cytoplasmic calcium ([Ca2+]i), as well as release of prostacyclin and expression of the proto-oncogene c-fos, intracellular events that have been linked to [Ca2+]i rise in stimulated endothelial cells. Addition of U46619 to confluent fura 2-loaded endothelial cells caused a concentration-dependent rise in intracellular [Ca2+]i, with agonist concentrations of 300 nM producing a maximal [Ca2+]i rise. This [Ca2+]i rise was a uniform response observed in all individual endothelial cells throughout the monolayer, as shown by microspectrofluorimetric visualization. Similar effects were seen with a structurally dissimilar endoperoxide analogue, I-BOP, and with the naturally occurring endoperoxide PGH2. The initial [Ca2+]i rise was not reduced when extracellular [Ca2+]i was chelated with EGTA, but a later "plateau" phase was eliminated. An antagonist of the receptor for TxA2/PGH2 (SQ29548) strongly inhibited [Ca2+]i mobilization. Stimulation of endothelial cells with U46619 also transiently increased expression of the proto-oncogene c-fos, as determined by RNA hybridization, and induced a fivefold increase in prostacyclin release. Thus, endoperoxides can stimulate human venous endothelial cells by means of TxA2/PGH2 receptors, whose occupancy can activate intracellular events associated with functional changes. PMID- 8477530 TI - Phosphatidylinositol metabolism in hypertrophic rat heart. AB - The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during cellular response to norepinephrine in pressure-overloaded hypertrophic rat heart. After stimulation with norepinephrine, the accumulations of IP3 and diacylglyceride significantly increased in isolated myocytes from stroke-prone spontaneously hypertensive rat (SHRSP) heart, indicating phosphatidylinositol specific phospholipase C activity increased in SHRSP heart cells. Protein kinase C activity was also enhanced in SHRSP, with a marked increase in particulate activity. We determined the intracellular calcium concentration and found it to be higher in SHRSP than in Wistar-Kyoto (WKY) rats at 30-40 weeks of age. Ca2+ influx was also elevated in SHRSP stimulated by norepinephrine. In SHRSP heart, cytosolic Ca2+ concentration may rise quickly in response to some stimuli, such as alpha 1-adrenergic stimulation, which is shown to be one of the pathways that increases cytosolic Ca2+ levels in hypertrophied rat heart. These data suggest that a part of the phosphatidylinositol-turnover pathway, such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride protein kinase C pathway, may play an important role in the development of hypertrophy in SHRSP heart. PMID- 8477531 TI - Mechanosensitive gating of atrial ATP-sensitive potassium channels. AB - Cell-attached and inside-out excised-patch recording techniques were used to search for mechanosensitive ion channels in neonatal and adult rat atrial myocytes. A channel activated by negative pressure applied to the patch, with a single-channel conductance of 52 pS in symmetric potassium solutions, was frequently observed. This channel has been identified as the atrial ATP-sensitive potassium (KATP) channel on the basis of its potassium selectivity, as well as its inhibition by ATP or tolbutamide in the inside-out excised patch. Mechanosensitive modulation of the KATP channel has not previously been reported. In the presence of 1 mM ATP, 10-50 microM pinacidil (a specific KATP channel agonist) does not significantly increase basal KATP channel activity; however, these concentrations of pinacidil potentiated the mechanosensitive modulation of the KATP channel. A hypotonic swelling protocol (a mechanical stimulus) was used in an effort to determine whether mechanosensitive modulation of this channel can generate significant whole-cell currents. Under perforated-patch whole-cell recording conditions, superfusion of atrial myocytes with a 240 mosm/kg solution (control solution, 290 mosm/kg) stimulated whole-cell currents with a magnitude similar to those activated by 10 microM pinacidil. These results demonstrate that the gating of the atrial KATP channel is mechanosensitive and suggest that mechanosensitive modulation may be an additional and significant mechanism, modulating channel activity under both physiological and pathological conditions. PMID- 8477532 TI - Issues confronting medicine. AB - Our representatives in Washington are attempting to deceive the American public with a giant prevarication. The electorate is being told that more patients can obtain better health care at a lower cost. The practicing dermatologist is caught between opposing forces that are demanding improved care in the face of dwindling reimbursements. Concomitantly, the inexorable forces and constraints of escalating office overhead, tort liability, bureaucratic red tape, and managed competition hang like a sword of Damocles over the head of the practicing dermatologist. The independent practitioner stands alone as the only advocate for his patient; however, the physician's plea to maintain the sanctity and dignity of the doctor-patient relationship is being sacrificed on the altar of cost containment. PMID- 8477533 TI - Major issues confronting the practicing dermatologist in the 1990s. AB - Protein issues confront the dermatologic practitioner in this last decade of the twentieth century, including 1) the role of managed care; 2) the decline of direct access to the specialist; 3) malpractice liability and the need for reform; 4) declining reimbursements in the face of escalating practice overhead; and 5) conflict between the individual's right to care and society's ability to subsidize that right. Correcting and improving the American health care system demands a return to the emphasis and values that made that system the envy of the entire world. We must re-emphasize the sanctity of the doctor-patient relationship, halt the incursion upon physician autonomy, and eliminate those third party factors such as insurance companies, bureaucrats, and administrators that accentuate commerce instead of compassion in medicine. It is hoped that by expanding and equalizing the American health care system, it is not made unpalatable and unresponsive to every citizen. PMID- 8477534 TI - Prioritization of health services. The Oregon Basic Health Services Act and its implications for dermatologists and patients with dermatologic disease. AB - The Oregon Basic Health Services Act was passed by the Oregon Legislature in 1989. This act mandates the provision of and payment for health services to Medicaid recipients based on a prioritized list of diseases and treatments. As a result of this legislation, Oregonians with incomes of 100% or less of the federal poverty level are eligible for Medicaid benefits. At present, families with incomes not exceeding 67% of the federal poverty level qualify for Medicaid in Oregon. The definition of prioritized care, how the prioritization was accomplished, and the potential effect of the implementation of this plan for dermatology and patients with dermatologic disease is discussed. PMID- 8477535 TI - Universal health coverage. AB - Although over 12% of our gross national product is spent on health care, approximately 14% to 17% of Americans are not covered by any form of health insurance. The cost, benefits, and deficiencies of private insurance and government programs are discussed in this article. The increasing percentage of persons surviving into older age, improved technology, patient demands and expectations, administrative costs, medical malpractice and defensive medicine, and other factors contribute to the steadily increasing cost of care. Physicians must participate in health care reform or passively accept determinations made in their absence. PMID- 8477536 TI - The national health service and dermatology as a specialty. AB - The history and development of health care provision prior to and following the introduction of the National Health Service in 1948 is outlined. This article covers all aspects of the training of dermatologists and the development of dermatologic services currently in the United Kingdom. PMID- 8477538 TI - Hospital staff privileges for dermatologists. AB - All dermatologists need to work at both the national and the local level to make our national dermatologic organizations reflect our surgical skills. At the local level, we should seek to become well integrated into the hospital staff and to document our competency when we take courses to learn new techniques. As more dermatologists are granted hospital privileges and become respected as valuable members of their medical community, this will help dignify and legitimize all of us on every level. PMID- 8477537 TI - Canadian dermatology. AB - Canadian dermatology differs from the American system by a predominant referral system in most provinces and by universal health care scheme. Canadian certification requires 1 year of internal medicine training in addition to 3 years of clinical training. The Canadian Dermatology Association has formed several links with the American Academy of Dermatology and sponsors a similar sun awareness campaign. PMID- 8477539 TI - Physician advertising. AB - Practically nonexistent until the late 1970s, advertising by physicians has become commonplace. Although informational and educational advertising may contain information that potential patients may find to be useful, laudatory and predatory advertising are unethical and may be patently illegal. There is a conflict between the obligations of a physician to his patients and the intentions of advertising. The role of the Federal Trade Commission and state regulations are discussed. PMID- 8477540 TI - Ethics in pharmaceutical advertising. AB - Pharmaceutical manufacturing is one of the most financially lucrative industries in America due, in part, to massive marketing and advertising. The content of many symposia and medical journals as well as physician prescribing decisions seems to be influenced by the promotional efforts of pharmaceutical companies. In an effort to increase sales, the industry now advertises directly to the public. The role of the Food and Drug Administration and ethical standards established by medical organizations are discussed. PMID- 8477541 TI - Contract law: relationship between dermatologists and third-party payers. AB - The relationship between third-party payers and dermatologists is generally governed by a written contract. That relationship can be more beneficial to the dermatologist, and chances of liability may be decreased, both for breach of contract and for malpractice, if the dermatologist pays close attention to the language in the contract. All contracts are generally negotiable; detrimental language in the contract often may be removed or changed. This article presents information to help prepare dermatologists to review and negotiate contracts. PMID- 8477542 TI - The impact of professional liability on dermatologists. AB - Familiarity with and adherence to the above principles may not make you claim- or judgment-proof, but they should improve patient care in your office and decrease your exposure to medicolegal interventions. Always bear in mind that medical practice is not a right conferred upon you by virtue of your medical degree, but rather a privilege granted you by state statute and licensure. Inherent in this privilege are the following: 1. That you remain familiar with and comply with all state and federal laws governing the practice of medicine. 2. That you remain current in your continuing medical education, quality assurance, and loss prevention. 3. That you possess and exercise that degree of skill and learning commonly possessed and exercised by some physicians of your specialty in the same or similar communities at the same point in time. 4. That you maintain a valid license, DEA registration, and appropriate hospital credentialing. PMID- 8477543 TI - Future trends in dermatology. AB - If the specialty of dermatology is to enjoy a bright future in medicine, excellence in education and basic research, use of technologic advances, and advancement of our scientific and clinical knowledge through general and subspecialty dermatology must continue. The specialty needs to be unified and must learn to function in local, state, and federal governmental appropriations, regulations, legislation, and administration. The specialty needs to establish dermatologists as primary care physicians for dermatologic medical and surgical services. Dermatologists deliver the highest quality of dermatologic care and are cost-effective health care providers. The specialty of dermatology has developed a strong organizational structure to effectively deal with these six strategic components so as to afford a bright future for dermatology. Effective actions by the specialty will require increased participation by the constituents and continued involvement of the varied dermatology organizations. The future cannot be predicted with certainty, but a well-prepared society can continue its past success and look forward to a future beyond its highest expectations. PMID- 8477544 TI - International Foundation for Dermatology. A challenge to meet the dermatologic needs of developing countries. AB - The primary goal of the IFD, which serves under the aegis of the International Committee of Dermatology (the governing body of the International League of Dermatological Societies), is to improve dermatology and dermatologic care in rural areas and developing countries. The principal mission of the IFD is to create regional dermatology training centers in geographic areas of greatest need. The first such center, serving the 12 countries of the African Regional Health Community, is located in Moshi, Tanzania. After successfully completing a 2-year course, the emerging dermatology officers will return to their countries of origin to promulgate the information they have learned by teaching others. The second RDTC is located in Chimaltenango, Guatemala to serve 10 countries in the Caribbean basin by training auxiliary nurses to man health posts in rural areas in this region. All dermatologists in the developed world should view their responsibility to their profession and to those suffering from dermatologic diseases in developing countries as a challenge that can be met if we all labor together to ensure a better world for those who currently have minimal or no dermatologic care. Remember: Give a man a fish and you feed him for one day; teach a man to fish and you feed him for life! PMID- 8477545 TI - Treatment of leg ulcers. AB - Leg ulcers represent the most common chronic wound in our population. This devastating problem often cripples patients, many of whom are in the prime of their working years. The resulting morbidity and financial cost are extraordinary. Fortunately, with the right approach, the vast majority heal with simple ambulatory outpatient therapy. The essential requirements for treating leg ulcers include a thorough understanding of lower extremity anatomy, vascular hemodynamics, and the management of trophic and inflammatory skin changes. PMID- 8477546 TI - Vitiligo. An overview of therapeutic approaches. AB - Vitiligo often induces severe cosmetic disfigurement in patients. These patients must function in a society that places profound emphasis and social significance on appearance. Although physically healthy, many patients are greatly affected psychologically by the disease. Hence, concerted efforts should be made to treat these individuals. Despite the inherent difficulties in stimulating melanocytes to repigment vitiliginous lesions, a variety of medical, surgical, and adjunctive/alternative therapies benefit innumerable patients with vitiligo. These treatments may be used as monotherapies or combination therapies to achieve optimal results. PMID- 8477547 TI - Therapeutic applications of photopheresis. AB - Photopheresis is a useful therapy for advanced cutaneous T-cell lymphoma, particularly for Sezary syndrome. Additional conditions in which clinical studies have suggested a therapeutic role for photopheresis include certain autoimmune diseases and reversal of rejection of solid organ allografts. Because photopheresis is extremely well tolerated and evidence is lacking for a direct immunosuppressive effect produced by this therapy, randomized trials should be pursued to determine the full spectrum of clinical benefit of this novel therapeutic modality. PMID- 8477548 TI - A primer of facial chemical peel. AB - Facial chemical peel encompasses a plethora of procedures or techniques and so may be confusing. This should not blunt one's enthusiasm for what chemexfoliation can achieve. With the use of TCA, chemical peel is a safe, effective, elegant, and simple method for treating some common problems of photoaged, fair skin (Table 7). When a standardized technique is used, it is possible to quantify the therapeutic effects and to predict the outcome reliably. Variations of chemical peel will be used as clinicians try to achieve better results. If possible, variations from standard techniques should be scientifically studied and quantified to establish their safety and efficacy. The goal of chemical face peeling is not simply to achieve a deep or longer-lasting peel. The highest concentrations of TCA and phenol may cause full-thickness facial chemical burns and leave long-lasting scars. Therefore, variations on standard techniques provide only subjective, difficult-to-measure benefits. Conversely, standardized testing on the facial skin of patients is difficult and thus we chose an animal model. Clinicians, especially dermatologists, who want to perform chemical peel should know the indications. Using the procedures described here and in other articles, one can safely and reliably undertake facial chemical peel. PMID- 8477549 TI - Dermal filler materials. AB - Although soft-tissue augmentation is not a new cosmetic procedure and actually has been performed for centuries, the modern era has introduced filling materials that are both safe and effective to soften the features. When used appropriately, these substances also can produce alleviation of scars and even true augmentation of the face. Newer techniques are being developed to access extremely fine lines, especially around the eyes. As research continues into newer materials, more procedures will become available and be more accessible to physicians and patients as the search for the perfect material for soft-tissue augmentation continues. PMID- 8477550 TI - Neoplastic angioendotheliomatosis: a treatable "vascular dementia" occurring in an immunosuppressed transplant patient. AB - A 53-year-old right-handed woman presented with headaches and dizziness. She had been well for ten years following successful cadaveric renal transplantation and was taking prednisolone and azathioprine. Two months later she had more headaches with transient dominant hemisphere disturbances and then suffered a completed right hemisphere deficit. As this was recovering, she developed an ischemic optic neuropathy, Computerized tomography (CT) was then normal although CSF analysis showed lymphocytosis and high protein. Steroid trial led to dramatic symptomatic and clinical recovery. On tailing off steroids, progressive bilateral hemisphere disturbance occurred. She was bedbound, with fever, headache, incontinence and disturbed consciousness. New evidence of infarction in watershed territories on CT led to temporal lobe biopsy. Cortical arterioles and venules showed proliferation of lymphoid cells staining for leucocyte common antigen and B-cell markers characteristic of Neoplastic Angioendotheliomatosis (NAE). After chemotherapy she regained independence and mobility and CSF protein fell. This is the first case of NAE to our knowledge in association with immunosuppression for renal transplant and is further evidence that NAE is malignant lymphoma. Cerebrovascular disease is common in such patients, the simultaneous events in differing territories is typical of NAE. Response to chemotherapeutic agents occurred although the typical natural history was unchanged. PMID- 8477551 TI - Functional localization in the Onufrowicz nucleus in man. AB - Neuropathological examination of a patient who died 45 days after the rectal amputation revealed axonal reaction of the motor neurons mainly in the dorsomedial portion of the Onufrowicz nucleus. Apparently normal motor neurons were found only in the ventrolateral portion. Also found in the present case was the localized distribution of chromatolytic neurons in the sacral intermediolateral cell column. While the ventral portion of it showed chromatolysis, the lateral portion was well preserved. These findings are in accordance with those obtained from the animal studies which demonstrated the functional localization of the sacral motor neuron pools into the anorectal innervation centers and the vesico-urinary centers. PMID- 8477552 TI - Frontal arachnoid cyst. A case of bilateral frontal arachnoid cyst without clinical signs. AB - The purpose of this study is to report a case of a very large arachnoid cyst in a patient having spent a very active life and who had never presented any neurological or psychiatric symptomatology beside a dementia in the last years of her life. The gross examination of the brain revealed the presence of a voluminous frontal bilateral cyst, located in the midline and displacing laterally the frontal lobes, so they displayed a foliated aspect. Microscopically, the examination of the cyst walls confirmed its arachnoid origin and the cerebral cortex contained lesions typical for senile dementia. This case exemplifies the histological nature and the pathogeny of arachnoid cysts, in particular of congenital origin. This also shows that the very early occurrence of such a malformation does not prevent the development of functional neuronal pathways, owing to the important plasticity of the central nervous system. PMID- 8477553 TI - Temporal lobe pathology in amyotrophic lateral sclerosis. Do amyotrophic lateral sclerosis and Alzheimer's disease share a common etiological factor? AB - An autopsy study was performed on temporal lobe samples from 20 non-demented patients with amyotrophic lateral sclerosis (ALS), 17 age-matched non-demented controls and 4 Alzheimer's disease (AD) patients. Formalin fixed, paraffin embedded sections from the hippocampus with adjacent parahippocampal gyrus and from the superior temporal gyrus were stained with conventional and immunohistochemical stains. Immunohistochemical staining for the A4 protein was enhanced by pretreatment with 0.25% pepsin before 100% formic acid. The incidence and severity of AD-like pathological changes were similar in ALS patients and non demented controls. In both groups, pathological changes increased with age. This study does not support the hypothesis that ALS and AD share an etiopathogenetic background. PMID- 8477554 TI - Pleomorphic xanthoastrocytoma: report of two cases and brief review of the literature. AB - Two cases of pleomorphic xanthoastrocytoma (PXA) involving the temporal lobe are reported, both occurring in adolescents. This neoplasma is a recently described, rare variant of astrocytoma affecting the superficial cerebral cortex and meninges of children and young adults. The tumor is considered to arise from the subpial astrocytes of the superficial cortex. Electron microscopic examination and immunoperoxidase stains for glial fibrillary acidic protein (GFAP) are helpful in making a definitive histologic diagnosis. Despite its pleomorphic appearance, this type of supratentorial glioma appears to have a much better prognosis than other tumors from which it must be distinguished, such as high grade gliomas and meningeal sarcomas. In contrast to malignant gliomas, the pleomorphic xanthoastrocytoma does not appear to require aggressive postoperative radiation therapy or chemotherapy. Therefore, it is important to recognize and identify this type of glioma as a distinct entity. PMID- 8477555 TI - Lack of presystemic inversion of (R)- to (S)-ibuprofen in humans. AB - Presystemic inversion of (R)- to (S)-ibuprofen has been proposed but not directly examined in humans. We investigated the bioavailability of the enantiomers of ibuprofen in 10 healthy volunteers. Low-dose racemic ibuprofen (400 mg) was administered orally and intravenously (60-minute infusion), in random order. There were no significant differences between oral and intravenous doses for the area under the curve values, terminal rate constants, clearances, metabolite formation clearances, and serum protein binding for (R)- and (S)-ibuprofen. The bioavailabilities of (R)-ibuprofen and total ibuprofen were 0.92 +/- 0.11 and 0.95 +/- 0.08, respectively. The fractional inversion of (R)-ibuprofen was determined by two methods (stable isotope method and from the stereochemical composition of the urinary metabolites) that gave similar estimates of inversion for oral dosing (0.56 +/- 0.12 and 0.60 +/- 0.07, respectively) and intravenous dosing (0.56 +/- 0.09 and 0.60 +/- 0.06, respectively). We conclude that the bioavailability of both enantiomers of ibuprofen is complete and find no evidence of significant presystemic inversion. PMID- 8477557 TI - Simultaneous analysis of inulin and 15N2-urea kinetics in humans. AB - To elucidate the physiologic basis of multicompartmental systems used to model drug distribution, we studied inulin and 15N2-urea kinetics after simultaneous intravenous injection in five normal subjects. Distribution of both compounds was characterized by three-compartment models in which the central compartment corresponded to intravascular space. The mean distribution volumes of 0.164 +/- 0.009 L/kg (+/- SD) for inulin and of 0.670 +/- 0.143 L/kg for urea were similar to expected values for extracellular space and total body water, respectively. Distribution from intravascular space was kinetically heterogeneous, presumably reflecting differences in vascular beds supplied by either fenestrated and discontinuous capillaries or capillaries with a continuous basement membrane. Intercompartmental clearances of inulin and urea and the ratio of their free water diffusion coefficients were used to estimate blood flows and permeability coefficient-surface area products for the peripheral compartments. The sum of compartmental blood flows averaged 5.39 +/- 0.49 L/min and was similar to dual beam Doppler measurements of cardiac output (5.47 +/- 0.40 L/min). PMID- 8477556 TI - Inhibition by fluoxetine of cytochrome P450 2D6 activity. AB - Potent inhibition of cytochrome P450 2D6 (CYP2D6) in human liver microsomes by fluoxetine and its major metabolite norfluoxetine was confirmed (apparent inhibition constant values, 0.2 mumol/L). Several other serotonergic agents were also found to be competitive inhibitors of this genetically polymorphic enzyme. The O-demethylation ratio of dextromethorphan that expressed CYP2D6 activity in 19 patients receiving fluoxetine fell in the region of the antimode separating the O-demethylation ratio values observed in 208 extensive metabolizers from 15 poor metabolizers of a control group of healthy subjects. Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme. Other in vitro studies indicated that CYP2D6 catalyzes the O-demethylation of oxycodone to form oxymorphone. This reaction was inhibited by fluoxetine and its normetabolite in liver microsomes from both extensive and poor metabolizer individuals, indicating that these compounds are not selective inhibitors of CYP2D6 activity. PMID- 8477558 TI - Protein binding and ivermectin estimations in patients with onchocerciasis. AB - We measured ivermectin in plasma, urine, and saliva of nine patients with onchocerciasis. The aim was to establish pharmacokinetic parameters and to assess the most facile medium for use in monitoring compliance. Binding of ivermectin to plasma proteins in vitro was also investigated. The mean (+/- SEM) plasma values for the nine subjects were as follows: weight, 66.3 +/- 2.8 kg; dose, 11.11 +/- 0.4 mg; half-life, 56.50 +/- 7.01 hours; clearance, 142.5 +/- 22.6 L/kg; volume of distribution, 9.91 +/- 2.67 L/kg; area under the plasma concentration-time curve, 1545.3 +/- 190.5 ng/ml.hr; time to reach maximum concentration, 4.7 +/- 0.5 hours; and maximum concentration, 38.2 +/- 5.8 ng/ml. Ivermectin was not detected in the urine of any of the nine subjects. Low levels were found in saliva. Blood specimens remain the only reliable biologic fluid for assessment of compliance after ivermectin oral administration. Ivermectin binds specifically to human serum albumin. PMID- 8477559 TI - A pharmacokinetic evaluation of the second-generation H1-receptor antagonist cetirizine in very young children. AB - The pharmacokinetics of the second-generation H1-receptor antagonist cetirizine was studied in eight children younger than 4 years of age who were treated with a single dose of cetirizine solution (5 mg). These children were hospitalized with suspected allergic respiratory problems or recurrent respiratory tract infections. Blood samples were collected at 1/2, 1, 1 1/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine collection was performed in five of the samples. The findings obtained in children were compared with those obtained in 16 healthy young adults (mean +/- SD, 24.6 +/- 4.1 years) who received a single 20 mg dose. Cetirizine was absorbed more slowly in children (p = 0.006; mean +/- SD, 1.44 +/- 1.12 hours) than in adults (0.62 +/- 0.22 hours). The plasma elimination half life of cetirizine was significantly shorter in children (p < 0.001; 4.91 +/- 0.6 hours) than in adults (8.6 +/- 2.1 hours), and the clearance rate was significantly higher in children (p < 0.001; 1.48 +/- 0.41 ml/min/kg) than in adults (0.80 +/- 0.17 ml/min/kg). Urinary excretion of unchanged cetirizine was significantly lower in children (p < 0.001; 37.8% +/- 5.2%; n = 5) than in adults (57.7% +/- 11.8%). Therefore the metabolism of cetirizine is faster in young children than in adults. This effect must be taken into account in future pharmacodynamic studies in this age group. PMID- 8477560 TI - Dose-related effect of moxisylyte on maximal urethral closing pressure in patients with spinal cord injuries. AB - The effects of single intravenous doses of 0.25, 0.50, and 0.75 mg/kg moxisylyte on maximum urethral closure pressure were evaluated in a placebo-controlled double-blind experiment in 20 patients with spinal cord injuries. Pharmacodynamic testing was performed until 30 minutes, and blood pressure was assessed until 60 minutes. Our findings showed a dose-dependent decrease in maximum urethral closure pressure. At each individual time point, the three doses differed significantly from placebo. Ten minutes after dose administration the maximum effect (48% decrease) was obtained with 0.75 mg/kg. A significant difference in favor of the highest dose was shown from 15 to 20 minutes after administration. According to these findings and because 0.75 mg/kg was as well tolerated as the two other doses, such a drop in pressure indicates that the alpha-blocking agent moxisylyte may be an effective means of decreasing urethral resistance, with obvious implications for the management of urinary obstruction. PMID- 8477561 TI - Decreased angiotensin II response but unaltered cardiovascular pressor response to infused norepinephrine after sodium restriction and converting enzyme inhibition. AB - Although studies indicate that converting enzyme inhibitors such as captopril influence beta-adrenergic physiology, the data on alpha-adrenergic physiology is inconsistent. This study therefore examined the effects of captopril (50 mg/day for 5 days) during sodium restriction on the pressor response and on angiotensin II and neuropeptide Y levels to infused norepinephrine (0.01 to 0.1 micrograms/kg/min) in 17 hypertensive and 27 normotensive subjects. Angiotensin II increased significantly in response to infused norepinephrine during placebo administration (p < 0.001) but not during captopril administration (p = 0.15). Neuropeptide Y levels decreased in response to captopril (p = 0.02). Despite these changes the pressor response to infused norepinephrine was unchanged with captopril. These data support the conclusion that the antihypertensive action of captopril is unrelated to alterations in norepinephrine-mediated alpha-adrenergic pressor regulation. The finding of a decrease in neuropeptide Y levels may have relevance to the therapeutic effects of captopril. PMID- 8477562 TI - Quinidine enhances digitalis toxicity at therapeutic serum digoxin levels. AB - OBJECTIVE: To determine the effect of the digoxin-quinidine interaction on rate of in-hospital digitalis toxicity. METHODS: This was a prospective observational study over 9 months, set in two general medical wards. We studied consecutive patients (n = 141) who were receiving digoxin. Measurements included digitalis toxicity, defined by ECG criteria and resolution after stopping digoxin; all additional medications (including antiarrhythmics) continued. The observer was "blinded" to serum digoxin level and to concomitant drugs. RESULTS: Digitalis toxicity rates were as follows: digoxin alone, 4.9% (5 of 101 patients); with amiodarone or verapamil, 5.0% (1 of 20 patients); with quinidine, 50% (10 of 20 patients) (p < 0.01). No toxicity was seen at digoxin levels < 1.0 ng/ml. Toxicity at 1.0 to 2.0 ng/ml was as follows: digoxin alone, 1 of 41 patients; with quinidine, 4 of 15 patients (p = 0.014). Toxicity was similar at levels > 2.0 ng/ml: 4 of 8 patients and 7 of 11 patients, respectively. Independent relative risks and 95% confidence intervals (CI) of digitalis toxicity were as follows: serum digoxin, 9.1 (95% CI, 2.9 to 13.0); concurrent quinidine, 24.3 (95% CI, 3.4 to 124). There was a significant (p < 0.01) interaction between concurrent quinidine, serum digoxin of 1.0 to 2.0 ng/ml, and digitalis toxicity. CONCLUSION: The digoxin-quinidine interaction significantly increases digitalis toxicity, even in the therapeutic range of serum digoxin levels. PMID- 8477563 TI - Glutathione S-transferase mu polymorphism does not explain variation in nitroglycerin responsiveness. AB - OBJECTIVE: To determine whether the considerable interindividual variability in nitroglycerin-induced venodilation in humans is related to the polymorphic expression of the mu class of glutathione S-transferase (GST mu). Recently vascular glutathione S-transferase (EC 2.5.1.18) of the mu-class (GST mu), a polymorphic group of enzymes present in only about 60% of the population, have been identified and shown in vitro to possess high metabolic activity toward nitroglycerin. Their clinical relevance is unknown. DESIGN: Dose-response relationships to nitroglycerin were constructed in vivo measuring changes in compliance of dorsal hand veins in 26 healthy volunteers during local infusion of small amounts of nitroglycerin. Polymerase chain reaction was applied to detect the deoxyribonucleic acid sequence that codes GST mu in whole blood samples. RESULTS: The GST mu isozyme was present in 15 subjects (58%) and deficient in 11 subjects. Values for mean maximum venodilation (Emax) and dose rates producing 50% of Emax (ED50) were not significantly different between the groups with or without GST mu. The respective values were 98% and 103% dilation for Emax and 9 and 16 ng/min for ED50. There was no gender difference in the venodilatory response to nitroglycerin. CONCLUSIONS: Subjects lacking GST mu can clearly respond normally to nitroglycerin, and the large interindividual variability in nitroglycerin potency is not related to the expression of this polymorphic enzyme. Intersubject variability is therefore more likely to be the result of differences in the presence or activity of other vascular enzymes or in steps further distal in the venodilatory cascade. PMID- 8477564 TI - Analgesic efficacy and potency of two oral controlled-release morphine preparations. AB - MS Contin tablets and Oramorph SR tablets are two forms of oral controlled release morphine sulfate available for the alleviation of pain. Our objective was to compare their analgesic effects in a relative potency assay. In this study, 151 patients undergoing caesarean section or abdominal hysterectomy and reporting moderate or severe postoperative pain received a 30 or 90 mg dose of either drug in a balanced, randomized, double-blind, parallel-group, single-dose experimental design. Patients provided self-ratings of analgesia. Relative potency for pain relief were calculated from log dose-effect curves. For total pain relief (rated by visual analog scales) over 12 hours, the log dose relative potency estimate for MS Contin tablets/Oramorph SR tablets was 1.9 (95% confidence limits, 0.89 to 11.1); for peak pain relief (visual analog scales) the relative potency estimate was 1.7 (95% confidence limits, 0.65 to 48.3). Overall, the 90 mg dose of MS Contin was more effective than 30 or 90 mg doses of Oramorph SR and the 30 mg dose of MS Contin at hours 6 to 12. Adverse experiences (mainly drowsiness) were mostly mild to moderate, with no significant differences in their overall incidence or severity between equivalent doses. MS Contin tablets provided greater peak, total, and duration of analgesia, without higher incidence of adverse experiences. PMID- 8477565 TI - Perindopril as monotherapy in hypertension: a multicenter comparison of two dosing regimens. The Perindopril Study Group. AB - Perindopril erbumine, a new long-acting, non-sulfhydryl-containing angiotensin converting enzyme inhibitor, was evaluated in 289 patients with hypertension in a 16-week, double-blind, placebo-controlled dose-ranging study. After 4 weeks of single-blind placebo treatment, patients with supine diastolic arterial pressures from 95 to 114 mm Hg were randomized to receive placebo, 4 mg perindopril once daily, or 2 mg perindopril twice daily. The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day. Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo (p < 0.05). The dose-response curve flattened after 8 mg per day, and there was no difference in arterial pressure reduction or in the percentage of responders between once- and twice-daily administration of perindopril. Adverse reactions with perindopril were generally mild and, with the exception of cough, were similar with placebo. The findings of this study indicate that perindopril is effective, well tolerated, and suitable for once-daily administration for the treatment of hypertension. PMID- 8477566 TI - Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. AB - In a study in the United States, Sweden, and Hungary, 335 cases of gastric bleeding without predisposing factors were compared with 670 control subjects, and 239 cases of duodenal bleeding were compared with 489 control subjects. For aspirin taken at least every other day during the week before the onset of bleeding (regular use), the relative risk of gastric bleeding was 4.4 (95% confidence interval [CI], 2.9 to 6.7); for occasional use, it was 3.3 (95% CI, 2.1 to 5.0). For ibuprofen, the corresponding estimates were 1.0 (95% CI, 0.4 to 2.6) and 1.1 (95% CI, 0.5 to 2.4). For naproxen, the estimate for regular use was 4.0 (95% CI, 1.5 to 11). The estimates for any use of piroxicam (crude estimate), indomethacin, and diclofenac during the week before onset were 18 (95% CI, 4.1 to 83), 1.6 (95% CI, 0.4 to 5.9), and 0.9 (95% CI, 0.2 to 4.2), respectively. The corresponding relative risks of duodenal bleeding were 7.1 (95% CI, 4.2 to 12) and 2.2 (95% CI, 1.3 to 3.7) for the regular and occasional use of aspirin, 2.4 (95% CI, 0.5 to 11) and 0.8 (95% CI, 0.3 to 2.0) for ibuprofen, 12 (95% CI, 2.8 to 54) and 9.9 (95% CI, 2.3 to 44) for naproxen, 17 (95% CI, 3.6 to 79) for any use of piroxicam (crude estimate), and 1.7 (95% CI, 0.2 to 14) for any use of indomethacin. There was a significant trend in the risk of gastric bleeding with increasing dose of regular aspirin use (p = 0.002). The relative risk estimates for the regular use of 325 mg or less were significantly elevated for both gastric and duodenal bleeding at 3.1 and 6.4, respectively. PMID- 8477567 TI - Publication bias. PMID- 8477568 TI - Industrial publication of controlled clinical trial data. PMID- 8477569 TI - Industrial publication of controlled clinical trial data. PMID- 8477570 TI - 1993 Clinical Research Meeting. Washington D.C., April 30-May 3, 1993. Abstracts. PMID- 8477571 TI - Scientists, societies, and science education. PMID- 8477572 TI - Effect of antibiotics on endotoxin release from gram-negative bacteria. AB - Antibiotics may inhibit bacterial growth or may kill bacteria by inhibiting cell wall synthesis or protein synthesis. The amount of endotoxin released during antibiotic action has been found to be clinically important. Nine antibiotics, representing seven classes, were studied for the amounts of endotoxin released during their action on susceptible strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. Staphylococcus aureus, which produces no endotoxin, was used as a control organism. Aztreonam induced the highest release of endotoxin, whereas other antibiotics such as imipenem and the quinolones induced the lowest release of endotoxin. Although the quantities of endotoxin released are not easily explained from the established mechanisms of antibiotic action, our findings may have implications for therapy of the acutely ill, septic patient in whom release of large quantities of endotoxin may be catastrophic. PMID- 8477573 TI - Multilaboratory evaluation of the in vitro activity of 13 beta-lactam antibiotics against 1474 clinical isolates of aerobic and anaerobic bacteria. AB - The in vitro activity of 13 beta-lactam antibiotics against 1474 recent clinical isolates was evaluated in a multilaboratory study. The most active antibiotic tested in this study was imipenem (98.5% of the strains were susceptible), followed by ticarcillin-clavulanate (91.4%), cefoperazone (90.0%), ceftazidime (87.9%), cefotaxime (87.7%), ceftriaxone (87.0%), ceftizoxime (86.3%), cefotetan (78.5%), ampicillin-sulbactam (77.9%), cefoxitin (73.5%), cefuroxime (70.9%), cefonicid (64.5%), and cefazolin (57.9%). PMID- 8477575 TI - Drug intolerance to high-dose clarithromycin among elderly patients. AB - We treated 13 elderly patients with chronic mycobacterial lung disease with clarithromycin using 1000 mg b.i.d. as monotherapy. Patients had a mean age of 70 years, and 12 of 13 had creatinine clearances of 31-71 ml/min. Adverse events were seen in 100% of patients, with the most common being bitter taste (92%), nausea (92%), vomiting (54%) and central nervous system symptoms (54%). Elevated liver enzymes developed in five (38%) of 13 patients at weeks 1-6 of therapy. Mean serum levels of clarithromycin plus its 14-OH metabolite were 12.9 +/- 3.6 micrograms/ml (SD). There were 11 patients (85%) who discontinued the high dose within 3 months because of side effects. Serum drug levels of clarithromycin plus its 14-OH metabolite consistently exceeded 12 micrograms/ml in six of six patients who discontinued drug (10 of 10 values) compared with neither of two patients who tolerated the high dose (0 of 6 values). A dose reduction to 500 mg b.i.d. was well tolerated (nine of 10 patients). Future trials with clarithromycin in this population should use lower doses with attention to body mass and renal function to minimize side effects. PMID- 8477574 TI - Occurrence of macrolide-lincosamide-streptogramin resistances among staphylococcal clinical isolates at a university medical center. Is false susceptibility to new macrolides and clindamycin a contemporary clinical and in vitro testing problem? AB - A total of 2189 staphylococcal strains at the University of Iowa Hospitals and Clinics (Iowa City, IA) were initially screened to determine the incidence of constitutive (29.8%) and potential inducible macrolide-lincosamide-streptogramin (MLS) resistance (11.3%). Staphylococcus haemolyticus and S. epidermidis (62.5% and 55.3%) showed the highest incidence of constitutive resistance. Staphylococcus hominis had the highest incidence of inducible resistance (40.6%), while S. aureus had the lowest rate for both resistance types. The overall ratio of constitutive-inducible MLS resistance was 4:1. Among strains initially speciated using the Vitek System GPI card, there was only a 69% species identification reproducibility, and 78% accuracy versus a reference identification method. A random sample of 105 Staphylococcus spp. isolates with discordant macrolide (erythromycin resistant) and lincosamide (clindamycin susceptible) susceptibility patterns were tested against 16 antimicrobial agents by using a reference broth microdilution method. All erythromycin-resistant Staphylococcus spp. were also resistant to other 14-member macrolides and azithromycin, while all organisms remained susceptible to clindamycin, rifampin, vancomycin, and the streptogramin compounds (RP59500 and virginiamycin). Resistance to teicoplanin was identified among some oxacillin-resistant S. haemolyticus strains. Of 105 isolates, 65 (62%) showed inducible MLS resistance, 28 (27%) were noninducible, and 12 (11%) were either fully susceptible or resistant to the MLS drugs (Vitek System interpretation errors). MLS disk induction tests revealed two inducible resistance phenotypes: ML and MLS. Staphylococcus aureus showed the highest inducible resistance rate at 95% with an MLS-predominant pattern. In contrast, endemic S. haemolyticus isolates did not demonstrate inducible resistance that is, efflux-mediated erythromycin resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477576 TI - RP 59500, a new streptogramin highly active against recent isolates of North American staphylococci. AB - To assess the potential clinical utility of RP 59500, 10 investigators from separate locations in the United States and Canada each tested approximately 200 current isolates of staphylococci (Staphylococcus aureus and coagulase-negative staphylococci) by a standard protocol. RP 59500 was highly active (MIC90 < or = 2 micrograms/ml) against all strains, including those that were resistant to oxacillin, ciprofloxacin, erythromycin, and spiramycin. PMID- 8477577 TI - The role of the clinical microbiology laboratory and the clinical pharmacy in the management of infectious disease (ASM, 1992). Introduction. PMID- 8477578 TI - Qualitative susceptibility tests versus quantitative MIC tests. AB - Qualitative susceptibility categories show reasonable, but incomplete, correlation with therapeutic outcome. Studies using quantitative MIC tests have demonstrated that treatment failures within the susceptible category are associated with higher minimum inhibitory concentrations (MICs) than with therapeutic successes. Other trials have exhibited enhanced response for increasing ratios of a pharmacokinetic parameter to MIC (for example, peak level to MIC ratio for aminoglycosides). Dose-response studies in animal infection models also demonstrate an excellent correlation between the dose of drug required for a given response and the infecting organism MIC. These studies suggest that the use of quantitative MIC tests may enable more individualization of the therapeutic regimen, especially in regards to dose and dosing frequency, than provided by qualitative category susceptibility tests. However, there are only rare studies that have used MIC results or pharmacokinetic parameters to improve efficacy. Furthermore, these studies have not consistently documented enhanced clinical efficacy. MICs can also be used to reduce drug dosage and cost of antimicrobial therapy for very susceptible organisms. Additional studies are clearly needed to define the full potential of the quantitative MIC test result. PMID- 8477579 TI - The impact of same-day tests versus traditional overnight testing. AB - Within the last decade, major technologic advances have been made in clinical microbiology that have resulted in the availability of a wide variety of different methods for the rapid reporting of test results. Included among these technologies are rapid methods for producing antimicrobial susceptibility reports that many regard as the most important information generated by the microbiology laboratory. Ideally, the early availability of this important information should favorably affect patient care by enabling the more judicious use of alternative drug therapies that are equally efficacious yet less toxic and less costly to the patient. Clinicians appear to have been reluctant to modify initial empiric therapies, however, despite the availability of the rapid antimicrobial susceptibility report. This article addresses some of the issues responsible for this long-standing problem and discusses and explores various strategies that can be implemented for improving the use and for controlling the cost of antimicrobial agents within the hospital. PMID- 8477580 TI - Selection of antimicrobial agents for routine testing in a clinical microbiology laboratory. AB - Each clinical microbiology laboratory must establish its own standard battery of antimicrobial agents to be tested routinely on clinical isolates of various organism groups. Some choices are based upon the intrinsic activities of antimicrobial agents for a particular group of organisms, for example, agents primarily active against either Gram-positive or Gram-negative bacteria. For final selection of limited batteries of agents for routine testing, however, it is necessary to use additional criteria based upon physician prescribing patterns and the availability of antimicrobial agents in a particular institution. A fundamental principle in the selection process should be routine testing and reporting of those antimicrobial agents that physicians actually use, that is, the institution's formulary agents. Testing of the most appropriate drugs for an institution may be complicated by lack of availability of some antimicrobial agents among the standard panels offered by automated instrument or commercial test system manufacturers. The laboratory should develop its final test batteries in consultation with the infectious disease and pharmacy services and the pharmacy and therapeutics and infection-control committees of the medical staff. These choices should not be made based upon the most convenient selection of drugs from the laboratory's perspective or based upon pharmaceutical industry promotional efforts. PMID- 8477581 TI - Effective reporting of susceptibility test results. AB - An overview of effective reporting of susceptibility test results is presented. Areas included in effective antimicrobial reporting are selective reporting of antimicrobials within drug families and by specific drug-organism combinations, automatic computer-delivered susceptibilities to patient-care areas, "flagged" results that are unusual and/or could seriously effect patient care, and the use of a coherent report format. Also included are areas that may significantly enhance antimicrobial result formats such as the reporting of cost information with susceptibility results, reporting "predictive sensitivities" based on institutional antibiograms, and reporting specific drugs for therapy based on gram's stain, and preliminary and final culture information. PMID- 8477582 TI - Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory. AB - Rapid reporting of culture and susceptibility data is the first of several important steps in the successful management of infected patients. As has been said many times, rapidly reported data are of little value unless the patient directly benefits. Benefit requires better overall communication and an action plan linked to timely use of these results. In 1989 the Millard Fillmore Hospital Antibiotic Review Committee developed and implemented a prototype approach to hospital wide antimicrobial management. The formulary was revised and the drug use evaluation process modified to enhance effectiveness and to lower the cost of therapy and inventory. Clinical pharmacy antimicrobial agent management specialists were then recruited to individualize patient treatments to the isolated pathogens in conjunction with the Division of Infectious Diseases. To provide the clinical pharmacy specialists with rapid and clinically useful information, a real-time computer link was created between the pharmacy (antibiotic orders) and the microbiology laboratory (culture results). Customized software was implemented to screen all patients automatically for mismatches between pathogens and drugs, or to screen for doses inappropriate to minimum inhibitory concentration or renal function. Special attention was paid to identification of opportunities to target a more appropriate narrow-spectrum regimen after culture results became available. Changes in antimicrobial regimen or dosage were made by contacting the prescribing physician. Over 90% of the recommended changes were made, and virtually all changed regimens had satisfactory clinical outcome. Real dollar expenditures for antimicrobial agents declined by > $200,000 per year. Prior to the institution of this computerized clinical management strategy, antimicrobial purchases were rising yearly at the rate of 12%-15%. The combined efforts of clinical pharmacy, microbiology, and infectious disease personnel successfully optimized antimicrobial therapy on a hospital wide basis. Antimicrobial agent optimization improved patient outcome, and the cost savings more than covered the costs of the program personnel and software. PMID- 8477583 TI - Formulary control of antimicrobial usage. What price freedom? AB - Formulary controls are the most common and probably the most effective method for controlling abuse of antimicrobial agents in hospitalized patients. Such programs may include restriction of both the number of agents available and the way these agents may be used. These programs have been demonstrated to control pharmacy expenditures. Other potential advantages include reductions in the incidence of adverse drug reactions and the antimicrobial resistance among the hospital flora, and improvements in the overall quality of prescribing of antimicrobials. There are few data to document such benefits, however. Potential disadvantages are also poorly documented but include inconvenience for prescribing physicians, increased administrative costs, prescribing errors, and increased antimicrobial resistance. Antimicrobial control programs will likely remain common, but the availability of new information technologies should enable a transition to systems based on concurrent assessment of antimicrobial appropriateness with immediate feedback to the prescribing physician. PMID- 8477584 TI - Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange. AB - This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process. PMID- 8477585 TI - A flexible, generic model for anatomic shape: application to interactive two dimensional medical image segmentation and matching. AB - A representation called a radial contour model (RCM) is described for two dimensional anatomic shapes. The model, which is a type of a geometric constraint network (GCN), is both flexible, in that it can deform to fit a particular instance of an anatomic shape, and generic, in that it captures all examples of a particular anatomic shape class. The model is implemented in a program, called SCANNER (version 0.7), for interactive model-based two-dimensional image segmentation and matching. Use of the model allows the segmenter to direct the search for edges in the image, and to fill in edges where none are present. Evaluations were done using models of 15 cross-sectional shapes appearing on CT images from 16 patients. Results from 480 trials show that the model-based approach reduces segmentation time by nearly a factor of 3 over manual methods, and correctly classifies 72.9% of the contours. The results not only suggest that the RCM will be useful for several current medical image segmentation tasks, but also support the hypothesis that geometric constraint networks are a viable approach to anatomic shape representation. PMID- 8477586 TI - Perusing the literature via citation links. AB - While MEDLINE searching is recognized as the single most effective means to identify relevant items to solve clinical and research problems, the clinician should also consider the complementary strategy to search for relevant items citing a known key paper. This study reports on the usefulness of citation searching based on the analysis of 89 searches. For each topic, the citations linked to an average of 24% additional relevant materials. At least one relevant item was added to 85% of the searches. The additional effort of scanning another printout is minimal since citation searching for 42% of the searches produced less than 7 additional items, half of which were judged to be useful. Duplicate retrievals were mostly of definite relevance. This alternate strategy appeared to be effective in interdisciplinary topics. Furthermore, the online version of the citation index is known for short turn-around time in processing, a feature important for many rapidly developing specialties. PMID- 8477587 TI - Neural network model: application to automatic analysis of human sleep. AB - We describe an approach to automatic all-night sleep analysis based on neural network models and simulated on a digital computer. First, automatic sleep stage scoring was performed using a multilayer feedforward network. Second, supervision of the automatic decision was achieved using ambiguity rejection and artifact rejection. Then, numerical analysis of sleep was carried out using all-night spectral analysis for the background activity of the EEG and sleep pattern detectors for the transient activity. Computerized analysis of sleep recordings may be considered as an essential tool to describe the sleep process and to reflect the dynamical organization of human sleep. PMID- 8477588 TI - Artificial neural networks as adjuncts for assessing medical students' problem solving performances on computer-based simulations. AB - Artificial neural networks were trained by supervised learning to recognize the test selection patterns associated with students' successful solutions to seven immunology computer-based simulations. New test selection patterns evaluated by the trained neural network were correctly classified as successful or unsuccessful solutions to the problem > 90% of the time. The examination of the neural networks output weights after each test selection revealed a progressive and selective increase for the relevant problem suggesting that a successful solution is represented by the neural network as the accumulation of relevant tests. Unsuccessful problem solutions were classified by the neural network software into two patterns of students performance. The first pattern was characterized by low neural network output weights for all seven problems reflecting extensive searching and lack of recognition of relevant information. In the second pattern, the output weights from the neural network were biased toward one of the remaining six incorrect problems suggesting that the student misrepresented the current problem as an instance of a previous problem. Finally, neural network analysis could detect cases where the students switched hypotheses during the problem solving exercises. PMID- 8477589 TI - Functional characteristics of QT prediction formulas. The concepts of QTmax and QT rate sensitivity. AB - A community-based population sample of 14,379 North American children and adults aged from birth to 75 years with normal ECG was used to investigate functional properties of 13 QT prediction formulas over a wide range of heart rates (HR) in normal sinus rhythm. QT measurements were made by a computer program from simultaneously sampled standard 12-lead or orthogonal XYZ leads and all QT measurements were visually verified using a high-resolution display terminal. New concepts of QT rate sensitivity (dQT/dHR) and maximum predicted QT after a long pause (QTmax) are introduced. Drastically diverging functional behavior is documented for different QT prediction formulas regarding QT rate sensitivity and QTmax. The simplest formula for predicted QT (QTp) meeting reasonable physiological constraints regarding QTmax and functional behavior of QT rate sensitivity while producing the best QT prediction accuracy was a function with only one independently adjusted parameter (QTmax) of the form: QTp = QTmax/(1 + 0.01HR), with QTmax = 656 ms. This formula also suggests that QT rate sensitivity is inversely proportional to the square of HR and that individual values of QTmax can be predicted from ambulatory or exercise ECGs using the formula QTmax = 2 x QT100, where QT100 is QT at HR = 100/min. PMID- 8477590 TI - The postoperative incidence of small bowel obstruction following standard, open appendectomy and cholecystectomy: a six-year retrospective cohort study at Yale New Haven Hospital. AB - The incidence of postoperative small bowel obstruction (SBO) after standard, open appendectomy and cholecystectomy was calculated during a six-year period at a university medical center hospital, which is the larger of two local, community hospitals. A cohort of 567 patients who underwent either a standard, open appendectomy or cholecystectomy from 1 October 1985 through 30 September 1986 was assembled. Of these patients, 182 (32.1%) were readmitted to the hospital prior to 1 October 1991 and thereby received follow-up. The time-related incidence of readmission to the hospital with a specific diagnosis of SBO as estimated by the Kaplan-Meier method was tabulated. This analysis revealed the following incidence rates of postoperative SBO: 10.7% following appendectomy during 64 months of follow-up (n = 41) and 6.4% following cholecystectomy during 67 months (n = 141). The Kaplan-Meier product-limit incidence of postoperative SBO was significantly different for standard appendectomy versus standard cholecystectomy (Breslow-Cox P value < 0.0277). This implies that the anatomical position and/or the likelihood of perioperative infection associated with open, abdominal surgery plays a significant role in subsequent adhesion formation and development of SBO. These data may be compared to laparoscopic techniques in future studies. PMID- 8477591 TI - Postoperative compartment syndrome and the lithotomy position: a report of three cases and analysis of potential risk factors. AB - There exists a definite association between the placement of patients in the modified lithotomy position and the development of postoperative compartment syndrome. It must be appreciated that this syndrome is potentially life threatening and frequently results in long-term sequelae. We report three cases which illustrate the problem and analyze the multifactorial etiology of this condition and propose a strategy for its prophylaxis. The combination of direct pressure on the posterior compartment of the calf, elevation of the legs above heart level, a number of intraoperative variables, the preexistence of any lower limb arterial insufficiency, and in some cases, the use of intraoperative compression boots, may lead to a state of hypoperfusion in the anterior and posterior compartment musculature. Upon completion of the operation, removal from the lithotomy position, and correction of the etiological factors, a reperfusion occurs with the development of a capillary leak with subsequent tissue edema causing an increase in compartmental pressure which may result in neurovascular compromise. This is the compartment syndrome. Emphasis must be placed on the identification of high-risk patients, the prevention or rapid correction of any etiological factors, the early diagnosis of the problem, and an aggressive approach to its treatment. PMID- 8477592 TI - Pregnancy related coronary artery dissection: a case report and collective review. AB - There have been 31 patients with pregnancy related coronary artery dissection reported in the medical literature. We report a case of both right and left coronary artery dissection in a postpartum patient. A collective review of the clinical course, risk factors, and treatment specific mortality rates of coronary artery dissection in near term and postpartum females is discussed. The mean age was 33, the mean parity was 2.7, and the mean time span was 20 days postpartum. Twenty-two percent had known risk factors for coronary artery disease. Eighty four percent involved the left anterior descending artery. Overall mortality was 66%. Of the patients that were alive on admission, 61% were treated medically (n = 11) with a 64% mortality; 39% were treated surgically (n = 7) with a 0% mortality. We conclude that pregnancy related coronary artery dissection occurs in otherwise healthy women near term or within three months postpartum. Multiparity and advanced maternal age may be risk factors. Early diagnosis and prompt surgical treatment may improve outcome. PMID- 8477593 TI - Practice locally, search globally. AB - The National Library of Medicine introduced the Grateful Med software package for accessing its databases over six years ago. Many new features have been added to the program since its inception in 1986. These major improvements enable health professionals to gain a more user friendly access to the biomedical literature of the National Library of Medicine than ever before. The software enhancements aid the end-user in performing searches that will retrieve material with greater specificity and accuracy. Grateful Med provides a time-saving, cost-effective means of equal access to the medical literature regardless of the user's physical location or lack of access to other resources. PMID- 8477594 TI - Social functions of the modern hospital. 1943. PMID- 8477595 TI - The anencephalic as organ donor: issues at the beginning and end of life. PMID- 8477596 TI - Listening to the patient, primary care, and reform. PMID- 8477597 TI - Multiple-organ dysfunction in the surgical patient: pathophysiology, prevention, and treatment. PMID- 8477598 TI - National American Academy of Dermatology conference on environmental hazards. PMID- 8477599 TI - Four flushers: topical agents producing facial flushing simulating the systemic variety. PMID- 8477600 TI - A dermatologic diary. Portrait of a practice. PMID- 8477601 TI - Infantile seborrheic dermatitis: an approach to cradle cap. PMID- 8477602 TI - The office visit and the self-help concept in treating the patient with psoriasis: a strategy revisited. AB - All dermatologists and physicians who care for patients with psoriasis should be aware that their patients may have an insufficient understanding of their disease. Every effort should be made to help patients fully comprehend their condition: to become aware of factors that can improve self-care and environmental events that can exacerbate the disorder. Strategies for self-help instructions can be modified from the highly structured approach in a university setting to the more informal atmosphere of a physician's office using the abundant patient educational resources available today. Improving communication between patient and physician will benefit the patient, by providing knowledge about psoriasis, encouraging the patient to acquire specific skills in dealing with the disease, and instilling a sense of responsibility for the patient's involvement in self-care. PMID- 8477603 TI - Fleas. PMID- 8477604 TI - Stethoscope dermatitis: an unusual presentation. AB - A medical intern presented with a rash that proved to be an unusual presentation of stethoscope dermatitis, a form of nickel contact dermatitis. The stethoscope as a cause of occupational side effects is reviewed. PMID- 8477605 TI - Calcifying panniculitis and systemic calciphylaxis in an end-stage renal patient. AB - A patient with a history of end-stage renal failure who had been receiving hemodialysis for approximately six months experienced painful plaques bilaterally on the medial aspects of her thighs. A biopsy specimen of the affected subcutaneous tissue demonstrated calcification in the subcutaneous tissue. In this case of calcifying panniculitis, the conditions for systemic calciphylaxis appear to have been present. PMID- 8477606 TI - The sign of Leser-Trelat associated with adenocarcinoma of the rectum. AB - The authors report a case of the sign of Leser-Trelat occurring in a patient with primary adenocarcinoma of the rectum. The patient demonstrated the sign several months before the internal malignancy was discovered. Although the majority of patients with the sign have an underlying adenocarcinoma of the gastrointestinal tract, relatively few cases have been reported with the rectum as the primary site. This case demonstrates a classic example of the sign of Leser-Trelat and illustrates its importance as a marker of underlying malignancy. PMID- 8477607 TI - Successful treatment of pyoderma gangrenosum with topical 5-aminosalicylic acid. AB - Pyoderma gangrenosum in a twenty-nine-year-old woman with associated long standing Crohn's disease was treated with topical 5-aminosalicylic acid cream. Significant improvement in the ulceration occurred despite progressive deterioration of the inflammatory bowel disease. The possible mode of action is reviewed. The efficacy, together with the lack of side effects, warrants further study into the therapeutic role of topical 5-aminosalicylic acid. PMID- 8477608 TI - Long-term follow-up of patients with diffuse fasciitis and eosinophilia associated with L-tryptophan ingestion. AB - We describe the long-term follow-up of two patients who experienced diffuse fasciitis and eosinophilia while ingesting L-tryptophan for treatment of insomnia. This is one of the first reports in the dermatologic literature of the long-term follow-up of eosinophilic fasciitis in association with L-tryptophan ingestion. Both patients fit the Centers for Disease Control's criteria for eosinophilia-myalgia syndrome. The literature on the eosinophilia-myalgia syndrome is reviewed. PMID- 8477609 TI - Cutaneous B-cell lymphoma associated with hypogammaglobulinemia. AB - A patient with hypogammaglobulinemia is presented with a primary cutaneous B-cell lymphoma. Diagnosis requires clinical and histologic criteria as well as phenotyping and genotyping. The cause, differential diagnosis, staging criteria, and treatment of the cutaneous B-cell lymphoma are reviewed. PMID- 8477610 TI - Transfer of bacteria associated with cryotherapy. AB - The aim of this study was to determine whether living bacteria can be transmitted by cryosurgery with carbon dioxide. Cultures were taken from the outer layer of the ice before starting treatment, and again at the end of the working day during ten consecutive working days. Each of ten dry ice blocks was sterile prior to use. Staphylococcus epidermidis was isolated from six of the latter following use. This finding indicates that the dry ice was contaminated during the procedure and that bacteria were transmitted from the patient's skin to the dry ice and to culture media. The medical implications of this finding require serious consideration regarding the risk of infection to both patient and clinical personnel from this procedure. PMID- 8477611 TI - Acquired lateral telangiectatic nevus: port-wine stain or nevus flammeus. AB - Three adult patients (one man and two women) with acquired lateral telangiectatic nevus (acquired port-wine stain or acquired nevus flammeus) on the face are presented. One patient had no history of preceding trauma. However, in two others, chronic sun exposure probably caused actinic damage of the skin with telangiectasia. A review of the literature on acquired lateral telangiectatic nevus and its causative factors is presented. PMID- 8477612 TI - Linear basal cell carcinoma. AB - Linear basal cell carcinoma is a rare morphologic variant of basal cell carcinoma. We present two cases of linear basal cell carcinoma. Both cases, treated by Mohs' micrographic surgery, demonstrated that there was lateral spread of the tumor that was not clinically present. PMID- 8477613 TI - Fijian penis marbles: an example of artificial penile nodules. AB - Artificial penile nodules are inert objects inserted beneath the skin of the penis to enhance the pleasure of female sexual partners during intercourse. The practice is most common among men from southeast Asia. This report describes a Fijian man who had an artificial penile nodule made from a whittled-down plastic toothbrush handle. Although some authors believe that the use of artificial penile nodules arose after World War II, the practice was discussed in the Kama Sutra, the classic Indian treatise on love. PMID- 8477614 TI - Sjogren-Larsson syndrome: report of a case in India. AB - The case of a six-year-old Indian girl with Sjogren-Larsson syndrome is reported. She displayed the classic triad of oligophrenia, ichthyosis, and spastic paraparesis. There was a history of parental consanguinity. The features that were absent were hypertelorism, pigmentary degeneration of the retina, simian creases of the palms, and aminoaciduria. PMID- 8477615 TI - Brittle nails: response to daily biotin supplementation. AB - A recent study from Switzerland demonstrated a 25 percent increase in nail plate thickness in patients with brittle nails who received biotin supplementation. Analysis of all visits to a nail consultation practice over a six-month period revealed forty-four patients with this condition who had been prescribed the B complex vitamin biotin. Of these, thirty-five who took daily supplementation were subjectively evaluated. Twenty-two of thirty-five (63 percent) showed clinical improvement and thirteen (37 percent) reported no change in their condition. The results of this small, retrospective study suggest a positive response to biotin in the treatment of brittle nails in some patients. PMID- 8477616 TI - Grandparent-headed families: new therapeutic challenges. AB - In today's complex society where dissolution of the nuclear family has become commonplace, grandparents are playing an increasingly significant role in the nurturing of their young grandchildren. The authors studied twelve randomly selected grandparent-headed families from the case files of a suburban child guidance clinic. Comparisons were made among the cases in terms of a number of factors, most significantly, elements of treatment including therapeutic issues, modalities and outcomes. The authors stress a multi-modal and intergenerational approach to the treatment of these families. PMID- 8477617 TI - Transitional objects, pre-sleep rituals, and psychopathology. AB - The prevalence among college age adults (N = 184) of transitional objects and pre sleep preparation rituals and their relationship to mental health was investigated. Two scales concerning use of transitional objects and fear of going to sleep, showed statistically significant correlations with self-reports of nightmares, loneliness, depression, and previous physical and sexual abuse. Forty six students scoring in the highest 15% of the distribution of scores for each scale were compared with students in the lowest 15% on the MAACL and SCL-90-R. High scoring students showed significantly higher levels of depression, anxiety, hostility, and interpersonal sensitivity. PMID- 8477618 TI - When emotionally troubled children grow up: adjustment in young adults who attended a psycho-educational treatment center. AB - This study examined post treatment outcomes of 88 young adults who attended a psycho-educational center for moderately to seriously emotionally troubled children. Over 60% made positive adjustment to adult life; the remainder were marginally functioning. Most subjects did not continue after high school with post-secondary education or vocational training nor did they or their parents receive individual and family therapy or supports from social services. Academic skills and parents' involvement in psycho-therapy were predictors of positive adjustment; child abuse was negatively correlated with adjustment. PMID- 8477619 TI - Academic achievement of children with emotional disorders treated in a day hospital program: an outcome study. AB - Reading, spelling, and arithmetic achievement of children treated in a day psychiatric hospital was examined over time. The results indicated that the majority of children fell in the average and above achievement group and progressed evenly over time. Almost none got worse and only a few made large gains. Organic impairment ratings appeared to distinguish the three performance groups within each subject area. PMID- 8477620 TI - Adolescent identity and delinquency in interpersonal context. AB - The relationship between delinquent involvement and the perceived importance of a variety of others in influencing, creating, and sustaining identity was explored in four subsamples (n = 238) of teens of varying levels of official delinquency. More delinquent teens were more likely to view conventional peers, delinquent peers and lifestyles, or no one at all as influencing their sense of self and identity. They were less likely to perceive parents and other adults as influential. PMID- 8477621 TI - Psychopathology and relationship measures in children with inflammatory bowel disease and their parents. AB - Children with inflammatory bowel disease and their parents were assessed for DMS III diagnoses, maternal attachment, marital relationship, life stresses, illness severity and cognitive/affective profile. Eleven of 15 children and 21 of 27 parents had psychiatric diagnoses. Three children were suicidal. Thirteen of 15 mothers had insecure attachment. Marital difficulties and medical severity correlated with life stress. The higher prevalence of psychiatric disorders than epidemiologically and of insecure attachment suggest at-risk relationships. PMID- 8477622 TI - Pretend play skills and the child's theory of mind. AB - Pretend play has recently been of great interest to researchers studying children's understanding of the mind. One reason for this interest is that pretense seems to require many of the same skills as mental state understanding, and these skills seem to emerge precociously in pretense. Pretend play might be a zone of proximal development, an activity in which children operate at a cognitive level higher than they operate at in nonpretense situations. Alternatively, pretend play might be fool's gold, in that it might appear to be more sophisticated than it really is. This paper first discusses what pretend play is. It then investigates whether pretend play is an area of advanced understanding with reference to 3 skills that are implicated in both pretend play and a theory of mind: the ability to represent one object as two things at once, the ability to see one object as representing another, and the ability to represent mental representations. PMID- 8477623 TI - Young children's conceptualization of pretense: action or mental representational state? AB - A growing body of research indicates that children do not understand mental representation until around age 4. However, children engage in pretend play by age 2, and pretending seems to require understanding mental representation. This apparent contradiction has been reconciled by the claim that in pretense there is precocious understanding of mental representation. 4 studies tested this claim by presenting children with protagonists who were not mentally representing something (i.e., an animal), either because they did not know about the animal or simply because they were not thinking about being the animal. However, the protagonists were acting in ways that could be consistent with pretending to be that animal. Children were then asked whether the protagonists were pretending to be that animal, and children tended to answer in the affirmative. The results suggest that 4-year-olds do not understand that pretending requires mental representation. Children appear to misconstrue pretense as its common external manifestations, such as actions, until at least the sixth year. PMID- 8477624 TI - Children's understanding of the stream of consciousness. AB - Children and adults were tested for their understanding that there is a virtually continuous flow of mental content in a waking person, a "stream of consciousness" that continues to run even when the person is not examining stimuli perceptually or trying to solve a problem. There was a marked increase with age from preschool to adulthood in subjects' tendency to say that a person who was just waiting quietly was having "some thoughts and ideas" rather than "a mind empty of thoughts and ideas." 4-year-olds also tended to say that the mind of a waiting person was "not doing anything," whether that person was another individual or themselves, and that a person who wanted to could keep his or her "mind completely empty of all thoughts and ideas" for 3 min. These results suggest that preschoolers' conceptions of people's mental lives may be quite different from those of older children and adults. PMID- 8477625 TI - Two roads diverged: young children's ability to judge distance. AB - In the present studies, we investigated 4- and 5- to 6-year-old's ability to compare the distances covered by a direct route to a location and an indirect route to the same location. The distances ranged between 16 and 22 feet. The routes were visible from a single vantage point, and objects serving as landmarks were sometimes located along the routes. We found clear demonstrations of the two classic Piagetian distance errors--the direct-indirect error, in which children judge that a direct route and an indirect route cover the same distance, and the interposed object error, in which children judge that a route is shorter when it is segmented by an object located somewhere along the route. The interposed object error occurred because children focused on only one segment of the route, which was consistent with Piaget's explanation of the error. However, in contrast to Piaget, we found that about 40% of 4-year-olds could successfully avoid the direct-indirect error, and in addition, when the routes were visually displayed, they could also avoid the interposed object error. It is important that they also gave correct explanations for why the indirect route was longer, by referring to the fact that it was not straight. For these children at least, the interposed object error was due to difficulty they had representing routes, rather than to a misconception of distance. We suggest that future research should examine whether that may also be true for younger children. PMID- 8477626 TI - Effective action by infants to contact objects by reaching and leaning. AB - The ability of infants aged 8-12 months to coordinate their arm and trunk movements to contact an object located in different positions was investigated in 2 experiments. In the first, 8- and 10-month-old infants reached for near objects but both reached and leaned for more distant ones indicating that they perceived that forward leaning extends the range of contact beyond that of reaching alone. In addition, arm and trunk movements were initiated simultaneously; visual information concerning object distance was sufficient to activate an integrated reaching-and-leaning response. Object distances were increased and a mechanical aid was provided on half the trials in the second experiment with 10- and 12 month-old infants. For both age groups the degree of leaning was reduced for objects that were out of reach without the aid. Only older infants were able to use the aid to extend partially their range of contact. Overall the results support the conclusions that, by at least 8 months, infants perceive that leaning extends their effective reaching space; by 10 months they perceive the limits within which reaching together with leaning is likely to be effective; and by 12 months they begin to perceive how this space may be extended by a mechanical aid. PMID- 8477627 TI - Conflict and friendship relations in middle childhood: behavior in a closed-field situation. AB - Disagreements between school-aged children were examined as a function of friendship status. 66 same-sex dyads were selected, including equal numbers of "best friends" and nonfriends, who were then observed while playing a board game (a closed-field situation). Conflicts occurred more frequently among friends than among nonfriends and lasted longer. Friends did not talk more during their conflicts than nonfriends, but assertions were used selectively according to friendship and sex: With friends, girls used assertions accompanied by rationales more frequently than boys whereas boys used assertions without rationales more frequently than girls. These sex differences were not evident during conflicts between nonfriends. Results are discussed in relation to the social constraints intrinsic to closed-field competitive conditions as they apply to friendship relations in middle childhood. PMID- 8477628 TI - The significance of gender boundaries in preadolescence: contemporary correlates and antecedents of boundary violation and maintenance. AB - Previous research has established the importance of gender boundaries as a normative aspect of development in middle childhood. Here, the nature and importance of gender boundaries as an individual differences construct was explored. Ratings of gender boundary violation and gender boundary maintenance were made of 47 10-11-year-old children participating in a series of summer day camps. These ratings were supported by videotape-based behavior codings of gender boundary violating behaviors and by live observations of sheer number of associations with members of the opposite gender. In addition, considerable external validation of these individual differences was obtained. Children low on gender boundary violation and (especially) children high on boundary maintenance were independently judged by camp counselors to be socially competent. They also were found to be higher on a friendship variable, based on observation. Those who violated boundaries were especially unpopular with peers, based on a child interview. Finally, boundary violation and maintenance were related to attachment history and to early measures of parent-child generational boundary distortions. PMID- 8477629 TI - Parenting practices and peer group affiliation in adolescence. AB - Social scientists have often assumed that parental influence is sharply curtailed at adolescence because of the rising counterinfluence of peer groups, over which parents have little control. The present study tested a conceptual model that challenged this view by arguing that parents retain a notable but indirect influence over their teenage child's peer associates. Data from a sample of 3,781 high school students (ages 15-19) indicated that specific parenting practices (monitoring, encouragement of achievement, joint decision making) were significantly associated with specific adolescent behaviors (academic achievement, drug use, self-reliance), which in turn were significantly related to membership in common adolescent crowds (jocks, druggies, etc). Findings encourage investigators to assess more carefully parents' role in adolescents' peer group affiliations. PMID- 8477630 TI - Emotional autonomy redux: revisiting Ryan and Lynch. AB - Ryan and Lynch have suggested that emotional autonomy in adolescence, at least as indexed by Steinberg and Silverberg's Emotional Autonomy Scale, is associated with poor family functioning and might therefore be better conceptualized as detachment. In the present study, we contrast adjustment scores among adolescents who differ in both emotional autonomy and perceptions of support in their relationship with their parents. Several thousand adolescents aged 14 through 18 completed Steinberg and Silverberg's emotional autonomy measure, a measure designed to assess the provision of support in the parent-adolescent relationship, and a number of standardized measures of adjustment. Adolescents high in emotional autonomy but low in relationship support show problematic adjustment profiles, consistent with Ryan and Lynch's interpretation of the measure as an index of detachment. Although adolescents high in both emotional autonomy and relationship support report more internal distress and behavior problems than some adolescents, they score higher on measures of psychosocial development and academic competence than their peers. Emotional autonomy in the context of a supportive adolescent-parent relationship may carry some developmental advantages as well as some deleterious consequences suggested by Ryan and Lynch. PMID- 8477631 TI - Emotional and cardiovascular responses to adults' angry behavior and to challenging tasks in children of hypertensive and normotensive parents. AB - Cardiovascular, overt-motor, and verbal-reported responses to interadult emotional expressions, including anger, and to challenging task situations were examined in a sample of 49 10-14-year-old children of hypertensive (EH) and normotensive parents (NT). Sons of EH parents showed greater systolic blood pressure reactivity to interadult anger and to the digit span task than sons of NT parents. A consistent pattern was not found for girls. Marital distress and overt maternal anger expression predicted verbal-reported and overt-motor responses to interadult anger. Family history of EH and sex did not predict these responses. Implications include (a) heightened systolic blood pressure response to stress may be found in sons of EH parents before they are diagnosed to have EH disorders, (b) relations between family history of EH and cardiovascular response may be sex moderated, and (c) vulnerability to stress may be related to specific familial histories and backgrounds. PMID- 8477632 TI - Social and emotional competence in children of depressed mothers. AB - The relation between maternal unipolar major depression and children's self concept, self-control, and peer relationships were studied in a middle-class, predominantly white sample of 96 families. Each family included a target child between the ages of 5 and 10. Depressed mothers varied on whether or not the child's father also had a psychiatric disorder. Well mothers all had spouses with no psychiatric disorders. Analyses controlled for marital status, age, and sex of child. Children completed measures of self-concept and peer relations skills; teachers completed measures of self-control and a rating of popularity with peers. Results supported the multiple risk factor model in that fathers' psychiatric status and parents' marital status explained much of the variability in children's social and emotional competence. Maternal depression alone, in the context of a well husband/father, was only related to children having been rated by their teachers as less popular. Results are discussed in terms of possible mechanisms by which maternal depression may interact with paternal psychopathology and divorce in relation to children's social and emotional competence. The findings may further indicate that older children are more vulnerable to these multiple risk factors than younger children. PMID- 8477633 TI - Greater preference among females than males for dyadic interaction in early childhood. AB - The present study was designed to examine sex differences in children's preferences for dyadic and group interaction in early childhood. In Study 1, a professional puppeteer interacted with 21 females and 20 males 4 and 5 years of age using 1 (dyad) and 3 (group) puppets in a within-subjects design. Enjoyment of the 2 conditions was assessed through frequency of smiling and eye contact. In addition, sociometric techniques were used to measure the size of children's play networks, and observations of naturally occurring dyadic and group interaction were conducted. Study 2 was a replication of the puppet play procedure used in Study 1 with 38 females and 37 males 3 and 4 years of age. In both studies, females were found to enjoy dyadic interaction more than males. In addition, some evidence suggests that males may enjoy group interaction more than females. Results are discussed in terms of theoretical explanations for sex differences in preferences for interaction with differing numbers of peers. PMID- 8477634 TI - Private speech of learning disabled and normally achieving children in classroom academic and laboratory contexts. AB - Learning disabled (LD) children are often targets for cognitive-behavioral interventions designed to train them in effective use of a self-directed speech. The purpose of this study was to determine if, indeed, these children display immature private speech in the naturalistic classroom setting. Comparisons were made of the private speech, motor accompaniment to task, and attention of LD and normally achieving classmates during academic seatwork. Setting effects were examined by comparing classroom data with observations during academic seatwork and puzzle solving in the laboratory. Finally, a subgroup of LD children symptomatic of attention-deficit hyperactivity disorder (ADHD) was compared with pure LD and normally achieving controls to determine if the presumed immature private speech is a function of a learning disability or externalizing behavior problems. Results indicated that LD children used more task-relevant private speech than controls, an effect that was especially pronounced for the LD/ADHD subgroup. Use of private speech was setting- and task-specific. Implications for intervention and future research methodology are discussed. PMID- 8477635 TI - Disorganized infant attachment classification and maternal psychosocial problems as predictors of hostile-aggressive behavior in the preschool classroom. AB - This study of 62 low-income families examined the relation between maternal and infant measures assessed at 18 months infant age and child behavior problems at age 5 as rated by preschool teachers. The infancy assessments included measures of mother-infant interaction, maternal psychosocial problems, infant cognitive development, and infant attachment security, including the disorganized/disoriented classification. The strongest single predictor of deviant levels of hostile behavior toward peers in the classroom was earlier disorganized/disoriented attachment status, with 71% of hostile preschoolers classified as disorganized in their attachment relationships in infancy. Maternal psychosocial problems independently predicted hostile aggression in preschool and combined additively with infant attachment security in prediction. Results are discussed in relation to the asymmetry of forward and backward prediction that characterized the findings and in relation to the potential significance of disorganized attachment behavior as a precursor to later maladaptation. PMID- 8477636 TI - Relation of rearing environment to adaptive behavior of Egyptian toddlers. AB - 2 questions were explored: (1) Do observed relations found in Western cultures between specific psychosocial environmental factors and toddlers adaptive behavior resemble the pattern of relations found in a non-Western setting? (2) Does the specificity of relations between environment and performance found in Western cultures also operate in a non-Western culture? Subjects were 153 Egyptian toddlers, 18-30 months of age, and their caregivers. Twice a month between 18 and 30 months toddlers were observed in naturalistic interactions with their caregivers, and measures of caregiver behavior and toddler functioning were coded. Replicating previous results from Western cultures, canonical analysis indicated that caregiver vocal stimulation was positively related to indices of toddler behavioral competence, while nonverbal response to vocalization and physical contact stimulation were negatively related. The salience of sib caregivers was also noted. Particularly for the age period between 24 and 29 months, results indicated specificity of environmental action such that measures of caregiver vocal stimulation were uniquely related to measures of toddler vocalization, while caregiver response to distress was uniquely related to toddler emotionality. The present pattern of results suggests at least some degree of cross-cultural generalizability of environment-development relations and of the specificity model of environmental action. PMID- 8477637 TI - Origins of attachment: maternal interactive behavior across the first year. AB - This study built on attachment theory and previous research in examining the interactional origins of the secure, insecure-resistant, and insecure-avoidant patterns of attachment. Maternal sensitive responsivity, rejection, and activity were the focus of repeated naturalistic observations when infants were 1, 4, and 9 months of age; quality of attachment was assessed at 1 year. Mothers of secure 1-year-olds were observed to be more sensitively responsive at 1 and 4 months and less rejecting at 1 and 9 months than mothers of insecure infants. Mothers of insecure-avoidant infants were more rejecting at 9 months, whereas mothers of insecure-resistant infants were least sensitively responsive and most rejecting at 1 month; the insecure groups were also differentiated on the basis of patterns of change from 1 to 9 months, with mothers of resistant infants becoming less rejecting and mothers of avoidant infants becoming more rejecting relative to other mothers. PMID- 8477638 TI - Behavioral organization in newborns and its relation to adrenocortical and cardiac activity. AB - The aim of this study was to assess relations between behavioral organization and adrenocortical and cardiac activity in newborns. Twice during the neonatal period, the behavioral organization of 42 newborns, in terms of orientation and irritability, was assessed by the Neonatal Behavioral Assessment Scale (NBAS), and the newborns' cortisol response to the NBAS procedure was determined. In addition, cardiac activity was assessed during 1 of the NBAS. Whereas there were only inconsistent correlations between newborn irritability and the adrenocortical response during NBAS, low orientation was associated with a higher increase in cortisol in both of the assessments. In addition, orientation was predicted by basal cortisol level. High heart rates were associated with high irritability and low regulation of state, and, in addition, negative relations were indicated between orientation and heart rate variability. The findings support a coping model of biobehavioral relations in newborns. PMID- 8477639 TI - Some complications of the therapy of hemorrhagic disorders. AB - The principal mode for treating disorders of hemostasis is correction of the patient's functional defect by transfusions of appropriate fractions of normal plasma or transfusions of platelets. Two major complications of such therapy are the transmission of infectious diseases, particularly hepatitis and the acquired immune deficiency syndrome (AIDS), and the development of antibodies against clotting factors that are deficient in the patient's plasma. Measures that reduce the occurrence of infection include careful selection of donors, fractionation of plasma with the help of monoclonal antibodies, and treatment of plasma or its fractions with heat or with virus-inactivating organic solvents. No technique of preparing or administering blood or its components can prevent the emergence of antibodies against clotting factors. Desensitization by repeated infusions of antigen, for example, antihemophilic factor, however, appears to result in remission in some patients. PMID- 8477640 TI - Inhibition of luteinizing hormone secretion by fasting and exercise: "stress" or specific metabolic signals? PMID- 8477641 TI - Suppression of luteinizing hormone secretion during short-term fasting in male rhesus monkeys: the role of metabolic versus stress signals. AB - One day of fasting leads to a significant suppression of pulsatile LH secretion in adult male rhesus monkeys that is evident within the first 4-6 h after a missed meal. Restricting food intake may suppress the central drive to the reproductive axis via metabolic signals occurring during the transition from a fed, energy storing state to a fasted, energy mobilizing state or via signals associated with the "psychological stress" imposed by withholding food. To distinguish between these two general types of signals, we chose the experimental strategy of providing monkeys with a great excess of calories on the day before fasting (i.e. overfeeding on the day before fasting) in order to maintain them in a metabolically fed state on the following day when they were fasted, without preventing the psychological stress associated with fasting. We reasoned that if metabolic signals are responsible for causing the fasting-induced suppression of LH secretion, overfeeding on the day before fasting would prevent the fasting induced suppression of LH secretion. Eight adult male rhesus monkeys with indwelling venous catheters were studied on three occasions: on a day of normal feeding (receiving approximately 30 pellets of monkey chow at 1100 h on the day of the study), on a day of fasting after a day of normal feeding, and on a day of fasting after a day of overfeeding (receiving one meal of 100 pellets on the day before the study). Pulsatile LH secretion on a day of fasting after a day of normal feeding (0.4 +/- 0.2 pulses/6 h, measured from 1200-1800 h) was significantly suppressed, P < 0.05, compared to a day of normal feeding (1.8 +/- 0.3 pulses/6 h). In contrast, on a day of fasting after a day of overfeeding there was no significant difference in LH secretion measured from 1200-1800 h (1.5 +/- 0.3 pulses/6 h) compared to a day of normal feeding. Overfeeding the day before fasting prevented the normal fasting-induced suppression of plasma T3 concentrations and delayed the normal fasting-induced decline in plasma insulin concentrations. Overfeeding did not prevent the display of agitated behavior that we have previously documented in monkeys when they are fasted. These results support the hypothesis that the signal(s) which suppresses normal LH secretion after brief periods of fasting is related to the metabolic status of the body during the transition from a fed to a fasted state, rather than a function of the psychological state imposed by withholding food. PMID- 8477642 TI - Reversal of fasting-induced suppression of luteinizing hormone (LH) secretion in male rhesus monkeys by intragastric nutrient infusion: evidence for rapid stimulation of LH by nutritional signals. AB - Short periods of fasting (1-2 days) significantly suppress the frequency of pulsatile LH secretion in adult male rhesus monkeys. Resumption of food intake (i.e. refeeding) after fasting rapidly restores pulsatile LH secretion. We hypothesized that the resumption of LH secretion after refeeding results from the metabolic consequences of food intake rather than from relief of the psychological stress associated with fasting. To differentiate between these two possible types of signals, we attempted to provide fasting monkeys with the nutritional signals of a refeed meal without relieving the psychological stress associated with fasting. To do this, we provided monkeys with a refeed meal via indwelling gastric cannulae while continuing to deny them access to monkey chow. Nine adult male rhesus monkeys with indwelling gastric and venous catheters were fasted for 1 day, and on the following day they received a liquid nutrient infusion (equal in caloric content and macronutrient composition to a normal meal) at the normal feeding time (1100 h) via the gastric cannulae. Blood samples were collected from 0600-2400 h at 20-min intervals. Nutrient infusions caused a restoration of pulsatile LH secretion that was not different from the restoration caused by refeeding a normal meal of Purina monkey chow. In contrast, LH secretion remained suppressed on a second day of fasting. Additionally, monkeys receiving nutrient infusions displayed behavioral agitation similar to fasting monkeys, while monkeys refed monkey chow showed very little agitation. These findings support the hypothesis that nutritional/metabolic signals, rather than the relief of psychological stress, lead to the resumption of pulsatile LH secretion after refeeding. PMID- 8477643 TI - Low doses of endothelin-1 inhibit atrial natriuretic peptide secretion. AB - To clarify the interaction between endothelin-1 (ET-1) and atrial natriuretic peptide (ANP), the effects of ET-1 on ANP secretion were investigated in isolated perfused rat hearts and in conscious unrestrained rats. Perfusion with 10(-9) M ET-1 stimulated ANP secretion from the isolated perfused rat heart. However, 10( 10) M ET-1 significantly decreased ANP secretion for the initial 15 min of the perfusion period. The perfusion with 10(-11) M ET-1, which is near the plasma level of ET-1 (2 x 10(-12) M), inhibited ANP secretion throughout the perfusion period. The perfusion of 10(-12) M ET-1 slightly decreased ANP secretion. After the ET-1 perfusion period, ANP secretion increased in proportion to ET-1 dose. The inhibitory action of ET-1 on ANP secretion was almost abolished by simultaneous perfusion of indomethacin, a cyclooxygenase inhibitor, but not by methylene blue, an inhibitor of soluble guanylate cyclase. In conscious unrestrained rats the iv infusion of 1 pmol/kg.min ET-1, which doubled the plasma ET-1 level, slightly but significantly decreased the plasma ANP level 5 and 10 min after the initiation of the infusion. The infusion of 10 and 30 pmol/kg.min ET-1 increased the plasma ANP level. These results demonstrate that low doses of ET-1 exert an inhibitory and short-acting action on ANP secretion from the heart, although high doses of ET-1 exert stimulating and long-lasting action, and suggest that prostanoids are involved in this inhibitory action. PMID- 8477644 TI - Early and late effects of angiotensin-II on Ca2+ fluxes in bovine adrenal zona glomerulosa cells. AB - Previous studies have yielded conflicting results concerning the effects of angiotensin-II (Ang II) on Ca2+ fluxes in adrenal zona glomerulosa (ZG) cells. The present study was designed to investigate the kinetics and dose-dependency of Ang II-mediated changes in Ca2+ influx and efflux in cultured bovine ZG cells. At a high (10 nM) Ang II concentration, cytosolic Ca2+ (Cai) shows a peak-plateau response for the first 15 min, with small Cai transients commonly observed with longer stimulations. At 50 pM Ang II, more sustained Cai changes were elicited, typically consisting of Cai oscillations. The underlying changes in Ca2+ influx and efflux were studied. The early modifications of Ca2+ influx after 2 min of agonist stimulation were biphasic, with uptake increased by 90% between 1-100 pM Ang II and inhibited by 30% at 10 nM Ang II. Furthermore, high (10 nM) Ang II doses inhibited extracellular K(+)-stimulated Ca2+ influx. After 30 min of Ang II stimulation, the later dose response of Ca2+ influx was of similar magnitude but shifted to the left, showing a maximal influx at 10 pM Ang II and a modest enhancement at 10 nM. Basal Ca2+ efflux followed a two-compartment exponential decay, reflecting rapid Ca2+ displacement from extracellular sites (k1) and active Ca2+ transport (k2). A high (10 nM) Ang II concentration induced a transient large increase (130%) in k2 during the initial phase of Ang II stimulation, which returned to basal values within 10 min. A low (50 pM) Ang II concentration induced a small sustained increase (30%) in k2. A 10-nM Ang II concentration markedly reduced the exchangeable Ca2+ pool, as Ca2+ mobilized from intracellular stores into the cytosol was rapidly extruded, while Ca2+ influx was inhibited. A more physiological (50 pM) concentration of Ang II did not significantly alter the total exchangeable Ca2+ pool due to modest stimulation of both Ca2+ efflux and influx. In summary, the initial transient Cai response to high Ang II results from a large Ca2+ mobilization combined with inhibition of Ca2+ influx, which does not allow for the refilling of Ca2+ stores. At later times, small increases in Ca2+ influx allow for the eventual recovery of exchangeable cell Ca2+ and an enhanced elevation in Cai. At low Ang II concentrations, stimulation of both Ca2+ influx and efflux are concurrent and maintained, allowing for a sustained increase in Cai with little change in exchangeable cell Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477645 TI - Intracellular calcium regulates insulin-like growth factor-I messenger ribonucleic acid levels. AB - Insulin-like growth factor-I (IGF-I) is involved in repair and regeneration in tissues in which non-GH-mediated regulation of its production has been shown to be important. We have investigated the effects of a second messenger signaling pathway, intracellular calcium, on IGF-I mRNA levels in cultured rat dermal fibroblasts using a RNase protection assay. Intracellular calcium concentrations ([Ca2+]i) were increased using either the calcium ionophore A23187 or thapsigargin. The ability of these agents to increase [Ca2+]i was confirmed by spectrofluorimetry, using fluo-3 as the Ca2+ indicator. Treatment of cells in serum-free medium and 0.25% BSA [Minimum Essential Medium (MEM) + BSA] with 500 nM A23187 or 1 micron thapsigargin decreased IGF-I mRNA levels in a time responsive manner over 4-8 h. A23187 and thapsigargin also decreased IGF-I mRNA levels to 36% and 47% of control levels, respectively, in a dose-responsive fashion. Basic fibroblast growth factor mRNA levels, which were simultaneously determined, were either unchanged or increased in cells treated with thapsigargin or A23187. Consistent with the change in IGF-I mRNA levels, immunoreactive IGF-I levels in medium conditioned for 48 h by A23187 or thapsigargin decreased to 25% and 14%, respectively, of control levels in cells maintained in MEM + BSA. To determine the role of protein synthesis in the effects of A23187 and thapsigargin, cells were treated with these agents in the presence or absence of cycloheximide. Cycloheximide had no effect on the decrease in IGF-I mRNA levels mediated by thapsigargin, but significantly attenuated the response to A23187. Given these differences in the role of protein synthesis in and the time course of the effects of A23187 and thapsigargin on IGF-I mRNA levels, additivity experiments were performed. Treatment of cells with the combination of A23187 and thapsigargin resulted in IGF-I mRNA levels that were approximately 70% of the levels present in cells treated with either agent alone. These data are consistent with a small additive effect, but suggest that the majority of the effect of A23187 and thapsigargin occurs via the same final pathway.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477646 TI - Differentiation of ovarian theca-interstitial cells in vitro: regulation of 17 alpha-hydroxylase messenger ribonucleic acid expression by luteinizing hormone and insulin-like growth factor-I. AB - Insulin-like growth factor-I (IGF-I) has been shown to synergistically augment LH stimulated androgen biosynthesis in ovarian theca-interstitial cells (TIC). Additional evidence suggests that IGF-I may play a role in stimulating TIC differentiation during early follicle development. The purpose of the present studies was to examine the role of IGF-I in TIC differentiation by determining the effects of IGF-I on P450(17 alpha) mRNA expression in TIC differentiating in vitro. TIC isolated from the ovaries of hypophysectomized immature rats by Percoll gradient centrifugation were cultured with and without LH and IGF-I for up to 6 days. At various times, cytoplasmic RNA was extracted from the TIC, and P450(17 alpha) mRNA was measured by a specific assay, using reverse transcription and the polymerase chain reaction. LH stimulated a dose-related increase in P450(17 alpha) mRNA, with an ED50 comparable to that for androsterone biosynthesis (33.0 +/- 3.8 ng/ml), but significantly less than the ED50 for cAMP accumulation (385 +/- 0.1 ng/ml). IGF-I alone did not stimulate P450(17 alpha) mRNA, but in the presence of LH (100 ng/ml) stimulated a dose-related (ED50, 4.1 +/- 1.6 ng/ml) increase (3-fold) in P450(17 alpha) mRNA. IGF-I did not alter the ED50 for LH stimulation of P450(17 alpha) mRNA (36.85 +/- 1.1 ng/ml). Detailed time-course studies revealed that IGF-I did not alter the 20-h lag phase before LH caused an increase in TIC androsterone biosynthesis; however, IGF-I stimulated a more rapid increase in androsterone than LH alone. In the presence of LH alone, P450(17 alpha) mRNA levels remained low for approximately 18 h, then increased rapidly to maximum levels by 30 h where they were maintained through 48 h. Concomitant treatment with LH plus IGF-I did not alter the 18-h lag phase, but P450(17 alpha) mRNA levels increased to approximately 2-fold higher levels than with LH alone. The results of our studies demonstrate that IGF-I increases the expression of P450(17 alpha) mRNA in TIC and support the hypothesis that IGF-I may play a role in stimulating thecal differentiation in developing follicles. PMID- 8477647 TI - Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching. AB - Ventricular hypertrophy is characterized by augmentation of the synthesis and storage of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). To evaluate in vitro the cellular mechanisms of immunoreactive ANP (IR-ANP) and BNP (IR-BNP) release from ventricular cardiocytes, we measured the secretory response to graded passive myocardial stretch in isolated atrialectomized perfused hypertrophied hearts of 14- to 18-month-old spontaneously hypertensive rats. At this age, the ventricular levels of both IR-ANP and IR-BNP were markedly higher in spontaneously hypertensive (182 +/- 27 and 32 +/- 3 pmol/ventricle, respectively) than in age-matched normotensive Wistar-Kyoto rats (35 +/- 4 and 12 +/- 1 pmol/ventricle, respectively; P < 0.001), whereas the differences between the strains in atrial levels of these peptides were small. The release of natriuretic peptides from ventricles in response to stretch was examined by increasing the volume of the intraventricular balloon for 10 min. Stretching of the hypertrophied ventricles produced a rapid transient (from 1-5 min) increase in both IR-ANP and IR-BNP secretion. As left ventricular pressure rose from 0 to 26 +/- 1 mm Hg, IR-ANP and IR-BNP release into the perfusion fluid increased 1.8 +/- 0.4- and 2.5 +/- 0.2-fold, respectively. Infusion of staurosporine, known to inhibit protein kinase-C activity in heart cells, blocked the stretch-induced increase in IR-ANP release (F = 3.10; P < 0.001, by analysis of variance), but had no effect on basal ventricular IR-ANP secretion (F = 0.87; P = NS). An L-type calcium channel antagonist, diltiazem, had no significant effect on basal (F = 1.20; P = NS) or stretch-stimulated (F = 1.47; P = NS) IR-ANP release from hypertrophied rat myocardium. Chromatographical analysis revealed that the ventricles primarily release the active processed 28- and 45- amino acid ANP- and BNP-like peptides, respectively, both before and during stretch. This study indicates that stretch stimulates both ANP and BNP secretion from hypertropic ventricular myocytes. The results further suggest that protein kinase-C may be involved in stretch-induced ventricular ANP release, whereas the influx of extracellular calcium may not be necessary. PMID- 8477648 TI - Enzyme characteristics of two distinct forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase complementary deoxyribonucleic acids expressed in COS-1 cells. AB - The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-Isomerase (3 beta HSD) catalyzes the conversion of delta 5-3 beta-hydroxysteroids to delta 4-3 ketosteroids, an essential step in the biosynthesis of all biologically active steroid hormones. We previously reported the isolation of three distinct mouse cDNAs for 3 beta HSD (3 beta HSD I, II, and III) and tissue-specific expression of their mRNAs. 3 beta HSD I is expressed only in gonads and adrenal glands, and 3 beta HSD II and III are expressed in both liver and kidneys. In the current study, we present data which demonstrate that transiently expressed 3 beta HSD I and 3 beta HSD III proteins can catalyze the conversion of the delta 5-steroids, pregnenolone and dehydroepiandrosterone, to their respective delta 4-3 ketosteroids, progesterone and androstenedione. They also can dehydrogenate the 3 beta-hydroxy group of the 5 alpha-reduced steroid 5 alpha-androstanediol to yield dihydrotestosterone in the presence of the cofactor NAD+. The Km values of the expressed 3 beta HSD I (for each of these substrates) were all below 0.2 microM. Km values of 3 beta HSD III were greater for all substrates, with the greatest increase observed for pregnenolone, which was over 10-fold greater. Both forms of expressed protein can catalyze the reduction of dihydrotestosterone to 5 alpha androstanediol in the presence of the cofactor NADH, but with considerably higher Km values (5.5 microM for form I and 6.8 microM for form III). The observed maximum velocity of form I was much higher for all substrates examined. RNase protection and immunoblot analysis of expressed 3 beta HSD I and III indicate that the difference in maximum velocity reflect differences in the steady state levels of mRNA and amounts of protein. In addition, the expressed 3 beta HSD III protein analyzed by Western blot has a lower mobility than the 3 beta HSD I protein, both similar in mol wt to the 3 beta HSD proteins detected in mouse liver and adrenal glands, respectively. These data demonstrate that an isoform of 3 beta HSD expressed in liver and kidney has the capacity to convert delta 5-3 beta-hydroxysteroids to delta 4-3-ketosteroids. The data suggest that a homologous human 3 beta HSD isoform could play an important role in cases of genetic deficiency of the gonadal and adrenal isoform. PMID- 8477649 TI - Sites of inhibition of steroidogenesis by activation of protein kinase-C in swine ovarian (granulosa) cells. AB - We tested the hypothesis that low density lipoprotein (LDL) metabolism and cellular concentrations of gene transcripts of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc mRNA) are sites of significant protein kinase-C (PKC) action in the long term (48-h) inhibitory modulation of steroid hormone biosynthesis in ovarian granulosa cells. To this end, we used 12-O tetradecanoylphorbol-13-acetate (TPA) as an activator of PKC and a monolayer culture system of immature swine granulosa cells responsive to insulin and lipoprotein under serum-free conditions. Insulin-regulated LDL metabolism was identified as a major site of TPA-mediated inhibition of steroidogenesis in granulosa cells. Treatment with TPA (30 ng/ml), but not inactive phorbol base, effectively decreased insulin-stimulated [125I]iodo-LDL binding by 75%, internalization by 90%, and degradation by 75%, as well as delivery and utilization of the [3H]cholesterol moiety of LDL in progesterone biosynthesis by intact granulosa cells. Cellular concentrations of P450scc mRNA, as measured by Northern blot hybridization with a 32P-labeled 1-kilobase porcine cDNA clone, were significantly increased by insulin. This insulin effect was virtually abolished by cotreatment with TPA (30 ng/ml). In contrast, accumulation of mRNA transcripts of a non-steroidogenic gene, 3-phosphoglyceraldehyde dehydrogenase, but not 18S ribosomal RNA, was enhanced by TPA. In summary, major inhibitory actions of PKC activation on granulosa cell steroidogenesis are expressed at specific loci of LDL metabolism, including LDL receptor number, internalization, and degradation, as well as the delivery and utilization of the [3H]cholesterol moiety of LDL to intact granulosa cells. Moreover, a PKC activator suppresses the intracellular accumulation of insulin-stimulated P450scc mRNA, but not that of phosphoglyceraldehyde dehydrogenase or 18S ribosomal RNA. The results obtained in this in vitro study suggest that the inhibition by TPA at these different sites along the steroidogenic pathway may be similar to that which occurs via hormones that work through the PKC system, such as prostaglandin F2 alpha. PMID- 8477650 TI - Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on the function of rat pituitary cells: tests in a long term superfusion system. AB - A novel class of targeted chemotherapeutic agents based on cytotoxic compounds linked to LHRH analogs was tested in a long term superfusion system in order to determine their effects on different types of rat pituitary cells. The compounds investigated included two cytotoxic LHRH agonists, T-98 ([D-Lys6]LHRH coupled to glutaryl-2-(hydroxymethyl)anthraquinone (G-HMAQ)) and T-107 ([D-Lys6]LHRH linked to doxorubicin (DOX) through glutaric acid spacer), and two cytotoxic LHRH antagonists T-121 and T-144, both containing two residues of G-HMAQ. The analogs were infused for 24 h at pharmacological (micromolar) concentrations. The secretions of LH, GH, and PRL cells after a short (2-h) and a long (20-h) recovery period following the treatment were compared to those before the analog infusion. All four cytotoxic LHRH analogs selectively decreased the stimulated LH response, while basal secretions of LH, GH, and PRL as well as the stimulated release of GH and PRL were not influenced in spite of the high doses applied and the long duration of exposure. The inhibitory effects of cytotoxic agonists and antagonists were significantly greater than those of their parent peptides. Equimolar concentrations of cytotoxic compounds alone (DOX or G-HMAQ), however, caused functional damage to all types of cells tested. To evaluate the mechanisms of the observed inhibitory actions, we compared the amount of LH released in response to 1) a specific stimulus to receptors (3 nM LHRH), 2) membrane depolarization with 100 MM KCl, not involving the receptor, and 3) the extraction of cells with 0.01 N HCl at the end of experiment. Cytotoxic LHRH agonists and their carriers caused depletion of LH pools, while cytotoxic LHRH antagonists or their parent peptides decreased the available binding sites for LHRH. The inhibitory effect of DOX on stimulated secretion of LH, GH, and PRL in our system could be due to an action on cell membranes. Our work indicates that in the pituitary cell superfusion system, targeted cytotoxic conjugates, based on LHRH analogs, selectively affect LH cells, in contrast to unconjugated cytotoxic compounds, which also damage GH and PRL cells. PMID- 8477651 TI - Glucocorticoid-induced increase in plasma corticosteroid-binding globulin levels in fetal sheep is associated with increased biosynthesis and alterations in glycosylation. AB - In fetal sheep, there is a concomitant prepartum rise in cortisol and corticosteroid-binding globulin (CBG) that maintains a low free plasma cortisol level and allows for a low negative feedback effect of cortisol on the secretion of ACTH from the fetal pituitary. However, the stimulus for the prepartum increase in CBG and the mechanism(s) of this effect are not known. It has been proposed that glucocorticoids increase CBG concentrations, and therefore, we infused fetal sheep with the synthetic glucocorticoid dexamethasone (DEX; 2 micrograms/min over 15 min every 2 h for 96 h, n = 5) or saline (n = 5). The plasma corticosteroid-binding capacity increased from 30.0 +/- 2.4 to 55.6 +/- 7.7 and 92.6 +/- 11.1 ng/ml at 48 and 96 h, respectively, of DEX infusion. To examine possible mechanisms of increasing fetal plasma CBG, we first cloned and sequenced a sheep CBG cDNA and purified the protein. This allowed us to deduce the primary structure of ovine CBG and to demonstrate that hepatic CBG mRNA abundance (single transcript of 1.8 kilobases) rose from 0.9 +/- 0.2 to 3.6 +/- 1.6 arbitrary units after 96 h of DEX treatment. Fetal DEX treatment produced a significant increase (7.1 +/- 1.2% to 13.1 +/- 1.4%) in the Concanavalin-A binding forms of CBG that predominate in adult sheep plasma. There was negligible transfer of purified [125I]CBG from the ewe to fetal plasma, urine, or amniotic fluid. We also injected adult sheep with DEX (10 mg/day for 4 days) and demonstrated a significant decrease in plasma corticosteroid-binding capacity by 24 h, which remained suppressed for the duration of the study. After 96 h of DEX treatment, there was also a significant decrease in adult hepatic CBG mRNA abundance. We conclude that glucocorticoids increase fetal plasma CBG in part by increased hepatic biosynthesis. It may also be accentuated by a change in the glycosylation of CBG, but cannot be attributed to transplacental transfer. Furthermore, glucocorticoid treatment exerts opposite effects on CBG biosynthesis in fetal and adult sheep. PMID- 8477652 TI - Human chorionic gonadotropin or human recombinant follicle-stimulating hormone (FSH)-induced ovulation and subsequent fertilization and early embryo development in hypophysectomized FSH-primed mice. AB - Adult hypophysectomized FSH-primed mice were used to study ovulation, fertilization, and preimplantation embryo development. Twelve days after hypophysectomy, animals were injected sc with oFSH (4 micrograms/day) twice a day for 3 days. This resulted in large preovulatory follicles that did not secrete estrogen. Concurrent with the last FSH injection, either hCG (5 IU) or human recombinant FSH (10 IU) was injected sc to induce ovulation. Animals were mated or not and killed 1-4 days later. The ovulation rate was similar for both the hCG induced group (FH) and the FSH-induced group (FF), 97% and 90%, respectively. About 45% of the FH mice mated successfully with 56% of the eggs fertilized compared to only 25% of the FF mice with 45% of the eggs fertilized. However, only 5% of ovulated eggs developed to four-cell stages in vivo by day 3 for the FH animals and none in the FF group. To determine the reasons for the in vivo retarded embryo development, embryos at the one- or two-cell stage were collected on day 2 from the FH group. After 96 h of culture, 22% of two-cell embryos were converted to blastocysts, and 11% of one-cell eggs divided to the four-cell stage. In contrast, 80% of two-cell embryos from normal mice develop into blastocysts by 72 h of culture. The ovarian incubation medium and serum were used to measure progesterone (P4), androstenedione (A), and estradiol (E2). The patterns of serum and in vitro production of steroids were parallel. In FH mice, P4 increased immediately on the day after hCG injection (day 1) and decreased progressively on days 2 and 3; A and E2 levels increased on day 2, A decreased on day 3, and E2 decreased on day 4. When human recombinant FSH was used to induce ovulation, there were no significant changes in serum P4 and A; E2 levels were about 4 times higher on day 1 than in the FSH-primed control, then dropped to baseline levels on days 2 and 3. However, on day 3 in both the FH and FF groups, FSH receptors were still present on the granulosa cells of antral follicles, and LH/hCG receptors were present on the granulosa cells of large antral follicles and newly formed corpora lutea.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477653 TI - Insulin-like growth factor I regulates c-myc and GAP-43 messenger ribonucleic acid expression in SH-SY5Y human neuroblastoma cells. AB - In the human neuroblastoma cell line SH-SY5Y, insulin-like growth factors I (IGF I) and II (IGF-II) are established mitogens, and IGF-I appears to promote SH-SY5Y neuronal differentiation. Studies show that c-myc gene product is a transcription factor associated with cell proliferation, and that c-myc messenger RNA levels decrease in differentiating SH-SY5Y neurons. Using Northern analysis we show that 24 h exposure of SH-SY5Y cells to IGF-I (3-10 nM) causes a 3- to 5-fold decrease in c-myc expression. The decrease in c-myc expression due to IGF-I is mediated via the type I IGF receptor and coincides with an IGF-I-mediated induction of the neuronal differentiation markers growth cone associated protein 43 and tissue type plasminogen activator. Under these conditions, IGF-I (10 nM) did not markedly affect the levels of Max messenger RNA expression. Thus, the differentiation promoting activity of IGF-I in SH-SY5Y cells in part due to IGF-I dependent regulation of the expression of genes involved in neuronal differentiation. PMID- 8477654 TI - Nerve growth factor and epidermal growth factor in mouse submandibular glands: identical diurnal changes and rates of secretagogue-induced synthesis. AB - The granular convoluted tubule cells of the mouse submandibular gland contain high concentrations of nerve growth factor (NGF) and epidermal growth factor (EGF). Levels of the two growth factors increase in parallel during development and after stimulation by thyroid hormone, androgens, and glucocorticoids, suggesting that similar controls regulate the production of both proteins. At the same time, however, the granular convoluted tubules hypertrophy, with resulting increases in glandular size and protein content. In this study, we have monitored changes in salivary concentrations of NGF and EGF in the absence of detectable changes in submandibular size or protein concentration. Both growth factors exhibited identical diurnal changes, peaking between 1200-2000 h. In addition, after secretagogue-stimulated release of the proteins into saliva, reaccumulation began after 2 h, with normal levels of both molecules attained 6 h posttreatment. These data indicate that submandibular NGF and EGF can be controlled by similar cellular or molecular mechanisms independent of the regulation of generalized growth responses. PMID- 8477655 TI - In vivo bioassay for the potency determination of human growth hormone in dwarf "little" mice. AB - Homozygous 40- to 90-day-old "little" mice (lit/lit), derived from the C57BL/6J strain, have been used to set up an in vivo body weight gain bioassay for GH whose performance has been compared to the widely used hypophysectomized rat assay. A log dose-response curve has been analyzed in order to choose doses in the linear range that are suitable for setting up useful, precise, and economical 2 x 2 factorial assays. A comparison between the response in the two sexes has also been carried out, showing no significant difference between male and female little mice of this age. Three assays have been carried out in these animals for the potency determination of a local human GH (hGH) reference preparation in terms of First International Standard of GH (human) for bioassay (WHO 80/505), comparing them to a classical assay in hypophysectomized rats performed with the same preparations. The calculated potency values were in good agreement, while the statistical parameters indicated a comparable assay precision, even in a practical and rapid 4-day assay. We suggest the substitution of hypophysectomized rats with little mice for this in vivo test, still required for potency and bioidentity determination of clinical preparations of recombinant hGH. This avoids the highly invasive, costly, and time-consuming surgery, providing a faster, more flexible, and economical assay method, while still directly measuring parameters of in vivo linear growth in an animal model closely related to isolated hGH deficiency type I. PMID- 8477656 TI - Differential effects of thyroid hormones on growth and thyrotropic hormones in rat fetuses near term. AB - We have studied the effects of thyroid hormone deficiency and excess on GH and TSH economy in the rat fetus near term. Pregnant rats were either left untreated (C group) or treated with methimazole to block thyroid function and infused with placebo, T4, T3, or both, until 21 days of gestation. Two experiments were performed: the doses (per 100 g body wt/day) of T4 ranging from 2.4-21.6 micrograms, those of T3 from 1.5-13.5 micrograms, with groups on 2.4 micrograms T4 + 1.5 micrograms T3. Fetal plasma T4 levels varied between 6-160% of C values and T3 values between 52-770%. Both plasma and pituitary GH decreased in hypothyroid fetuses from methimazole dams, and their plasma TSH was elevated. When T4 and/or T3 were infused, plasma and pituitary GH increased as a function of fetal plasma T4 and T3, reaching normal values when plasma T3 levels became normal, then increasing further. The effects on GH economy were related to the plasma T3 level, with no appreciable difference if T3 had been infused or derived from T4. In contrast, the elevated plasma TSH of the hypothyroid fetus decreased toward normal values when fetal plasma levels of T4, and of T3 derived from T4, became normal, but was not affected by normal fetal plasma T3 when T3 was infused. In the absence of T4, T3 decreased plasma TSH only when infused in doses that increased fetal plasma T3 3-fold above C values or more. Thus, both GH and TSH economy are under thyroid hormone control in rat fetuses near term. Similarities and differences with respect to regulation in adult rats cannot, however, be attributed exclusively to differences in fetal somatotrophs and thyrotrophs, because of the possibility that control is exerted at regulatory sites which are unique to the fetus. PMID- 8477658 TI - Insulin-like growth factor-II messenger ribonucleic acid expression in fetal tissues of the sheep during late gestation: effects of cortisol. AB - Using RNase protection analysis, insulin-like growth factor-II (IGF-II) mRNA levels were measured in various tissues from fetal sheep during late gestation (term, 146 +/- 2 days) and after experimental manipulation of fetal plasma cortisol levels. No gestational trend in IGF-II mRNA levels was observed in the fetal lung, kidney, or skeletal muscle. However, in the fetal liver, there was a marked decline in IGF-II mRNA abundance immediately before term, which closely paralleled the normal prepartum surge in fetal plasma cortisol. This decrease in hepatic IGF-II mRNA levels toward term was prevented when the cortisol surge was abolished by fetal adrenalectomy and was stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Hepatic and renal IGF-II mRNA abundances were also reduced when fetal cortisol levels were raised endogenously by maternal fasting in late gestation. Muscle IGF-II mRNA levels were reduced by fetal cortisol infusion, but not by maternal fasting, and were higher in adrenalectomized than in intact fetuses in late gestation. No change in IGF-II mRNA levels were observed in the fetal lung in response to altering the fetal cortisol level either exogenously or endogenously. When the data from all fetuses were combined regardless of treatment or gestational age, there was a significant inverse correlation between the plasma cortisol level in utero and IGF-II mRNA abundance in the fetal liver (P < 0.001), but not in any of the other fetal tissues studied. These findings show that cortisol suppresses IGF-II gene expression in the liver of the sheep fetus and indicate that the developmental change in hepatic IGF status toward term may be due to the prepartum cortisol surge. PMID- 8477657 TI - Bioactivity of human growth hormone in serum: validation of an in vitro bioassay. AB - GH, in clinical practice, is determined by RIA, but RIA estimates may not accurately reflect serum GH bioactivity. The available measures of GH bioactivity lack either sensitivity, specificity, or a physiologically relevant end point. The objective of this research was to develop a physiologically relevant GH bioassay which would not only measure the bioactivity of purified GH preparations, but would also have sufficient sensitivity to measure GH bioactivity in human serum. The method consisted of incubating murine 3T3-F442A adipocytes in serum-free medium containing BSA, 14C-glucose, and increasing concentrations of GH or test materials for 24 h, followed by measurement of conversion of glucose to lipid. Interference by nonspecific serum factors was reduced by the addition of 10 micrograms/liter insulin, 25 nM dexamethasone, and 37 nM estradiol to the medium. In the presence of 10 micrograms/liter insulin, 50 micrograms/liter insulin-like growth factor-1 did not alter the ability of GH to suppress lipid accumulation. Epinephrine and glucagon could suppress lipid accumulation but only at concentrations greatly in excess of the physiological range in serum. Twenty two thousand dalton hGH produced dose-dependent suppression of lipid accumulation which was linear between 0.625 and 10 micrograms/liter (r = 0.926; P = 0.0001) with a half-maximal response of 3.0 +/- 0.2 micrograms/liter (n = six experiments). The intra- and interassay coefficients of variation were 7% and 19%, respectively. The assay was specific for GH since addition of human PRL produced suppression of lipid accumulation only at concentrations where contamination of the preparation by GH became a significant factor. ACTH also suppressed lipid accumulation but only at doses of 1000 micrograms/liter or greater. Human placental lactogen and hLH, hFSH, and hTSH did not cross-react with GH in this assay. Addition of human serum did not alter the slope of ED50 of the GH dose-response curve. Pools of serum from prepubertal and pubertal boys and girls, subjects treated with arginine or insulin, a diabetic girl, and a boy with gigantism who had a serum GH content of 80 micrograms/liter by RIA and 40 micrograms/liter by bioassay, produced dose response curves parallel to that of the GH standard curve. Serum from patients with hypopituitarism did not produce significant suppression of lipid accumulation in any assay. Recovery of 5 micrograms/liter GH added to human serum was 94%. Twenty thousand dalton GH also suppressed lipid accumulation in this assay, but was 2-fold less potent than 22,000 dalton GH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477659 TI - Development of a specific and sensitive two-site enzyme-linked immunosorbent assay for measurement of inhibin-A in serum. AB - A polyclonal chicken antiserum against purified 32-kilodalton (kDa) recombinant inhibin-A (rh-InhA) and two monoclonal antibodies (mAb) against either rh-InhA (11B5) or 28-kDa recombinant activin-A (rh-ActA; 9A9) were used to develop three sensitive InhA enzyme-linked immunosorbent assays (ELISAs). The sensitivity of an ELISA using affinity-purified chicken anti-rh-InhA (Ck) for both coat and capture (Ck/Ck) averaged 78 +/- 3 pg/ml, while the mAb/Ck ELISAs (11B5/Ck or 9A9/Ck) averaged 100 +/- 6 pg/ml in a 10% serum matrix, with intra-and interassay coefficients of variation of 2-5% and 8-10%, respectively, for all assays. The ELISA formats did not cross-react with purified rh-ActA or recombinant human transforming growth factor-beta 1 or detect any immunoreactive proteins in medium conditioned by cell lines expressing rh-ActA or recombinant human transforming growth factor-beta 1. The Ck/Ck ELISA detected significant amounts of immunoreactivity in medium from cells expressing the free alpha-subunit of inhibin and recombinant inhibin-B (rh-InhB). In contrast, the mAb/Ck ELISAs showed no cross-reactivity to medium conditioned by these two cell lines. All three ELISA formats detected rh-InhA added to either human or rat serum in vitro or serum from rats injected with rhInhA. The Ck/Ck and 9A9/Ck ELISAs successfully quantitated inhibin in sera from patients undergoing ovulation induction and in rats (with or without sc administration of pregnant female serum gonadotropin). The 11B5/Ck ELISA appeared to be specific for the 32-kDa form of inhibin, while the 9A9/Ck ELISA was useful in quantitating inhibin-A in biological fluids, with little cross-reactivity to free alpha-chain or inhibin-B. PMID- 8477660 TI - Two molecular forms of gonadotropin-releasing hormone from the brain of the frog, Rana ribibunda: purification, characterization, and distribution. AB - The molecular forms of GnRH in amphibia have not been characterized structurally. An antiserum to mammalian GnRH that shows appreciable cross-reactivity with chicken GnRH-I ([Gln8]GnRH), chicken GnRH-II ([His5,Trp7,Tyr8]GnRH), and salmon GnRH ([Trp7, Leu8]GnRH) was used in a RIA to detect GnRH-related peptides in an extract of the brain of the European green frog, Rana ridibunda. Two peptides were purified to apparent homogeneity, and determination of their primary structures showed that they are identical to mammalian GnRH and chicken GnRH-II. Salmon GnRH and lamprey GnRH-I ([Tyr3,Leu5,Glu6,Trp7,Lys8]GnRH) were not identified in this species of frog. Immunocytochemical analysis using specific antisera has identified regions of the frog diencephalon and telencephalon in which chicken GnRH-II and mammalian GnRH are localized to different populations of neurons. This differential distribution suggests distinct physiological roles for the two forms of GnRH in amphibia. PMID- 8477661 TI - The type I iodothyronine 5'-deiodinase messenger ribonucleic acid is localized to the S3 segment of the rat kidney proximal tubule. AB - A complementary DNA clone encoding the type I iodothyronine 5'-deiodinase (5'DI), which converts T4 to T3, has been isolated recently. The 5'DI messenger RNA (mRNA) is most abundant in kidney and liver. To gain insight into the function of 5'DI in the kidney, Northern blot analysis was used to localize the expression of this mRNA. Our results show that 5'DI mRNA was expressed in the cortex and outer medulla, but not inner medulla and papilla, indicating that there are regional differences in its expression. Using in situ hybridization, we demonstrate that the 5'DI hybridization signal is localized predominantly over tubules in the outer stripe of the outer medulla and in medullary rays, suggesting localization to proximal tubules. To identify which tubular cells express 5'DI mRNA, we compared the profile of 5'DI message from in situ hybridization with the immunostaining of adjacent sections with proximal tubular S1, S2, and S3 segment specific antibodies. Most of the 5'DI antisense complementary RNA hybridized to the same proximal tubular cells with which the S3-specific antibody, anti-ecto ATPase, reacted. Cells staining with an S1 or S2 segment antibody showed little, if any, 5'DI mRNA. We conclude that the expression of 5'DI mRNA is restricted to the tubular cells of the proximal S3 segment. The S3 segment is also known to express high levels of proteins required for glutathione synthesis consistent with the requirement for a reduced thiol cofactor for iodothyronine deiodination by the 5'DI pathway. PMID- 8477662 TI - Spontaneous cytosolic calcium pulses in Xenopus melanotrophs are due to calcium influx during phasic increases in the calcium permeability of the cell membrane. AB - We recently discovered that melanotrophs of Xenopus laevis exhibit spontaneous pulse-like rises in cytosolic free calcium ([Ca2+]i) and that this cytosolic Ca pulsing is inhibited by the secreto-inhibitory transmitters dopamine, gamma aminobutyric acid, and neuropeptide-Y and stimulated by the secretagogues CRF and TRH. Here we provide evidence for the factors responsible for the individual cytosolic Ca pulse and the repetitive behavior. Isolated melanotrophs of Xenopus were loaded with fura-2, and fluorescence was recorded from perifused single cells to measure [Ca2+]i and assess the patency of divalent cation channels by Mn quenching of fluorescence. Cytosolic Ca pulsing was arrested by omission of Ca and by the Ca channel blockers Ni and Co, but was unaffected by tetrodotoxin. Mn (0.3 mM) caused phasic quenching, each "quench" being synchronous with the rising phase of a cytosolic Ca pulse. Quenching was blocked by Ni, but was unaffected by tetrodotoxin. When introduced during the course of an individual Ca pulse, Ni aborted the pulse and [Ca2+]i collapsed. Extracellular K+ (10 mM) or K channel block with tetraethylammonium stimulated Ca pulsing. Threshold concentrations of Ni slowed Ca pulsing without reducing the amplitude of the individual pulses. The overshoots in quenching and Ca pulsing observed after exposure to Ni, dopamine, or baclofen are interpreted as off responses. It is concluded that each cytosolic Ca pulse is attributable, probably quantitatively, to Ca influx during a spontaneous increase in Ca permeability independent of Na-mediated action potentials, and that the pacemaker for the repetitive phenomenon is voltage sensitive and may involve Ca currents active around basal membrane potential. PMID- 8477663 TI - In vitro evidence for atrial natriuretic factor-(5-28) production by macrophages of adult rat thymi. AB - Although recent evidence suggests the presence of the 15-kilodalton (K) mol wt (Mr) precursor of atrial natriuretic factor (ANF) and pro-ANF mRNA in the thymus of human and rat neonates, the cellular origin of the peptides in the tissues remains to be elucidated. We report here that in adult male rats, the 15K M(r) presumptive precursor for ANF and a smaller 3K M(r), N-terminal truncated congener of the peptide, ANF-(5-28), are localized in a small population of thymic macrophages. The production of ANF in the thymus was further confirmed by demonstrating the presence of a single band of pro-ANF mRNA signal of approximately 0.8 kilobases from the tissue extract, corresponding to that in the heart. To examine the distribution of pro-ANF mRNA at a cellular level, colorimetric in situ hybridization with digoxigenin-labeled 30-mer oligonucleotides complementary to the first 10-amino acid sequence of ANF-(1-28) was employed. Positive staining was found in thymic cells localized mainly in subcapsular areas, with diffuse staining of positive cells in both the cortex and medulla mainly concentrated around the cortico-medullary junction of the tissue. The identity of the ANF-positive cells was further investigated using a double staining technique to costain immunoreactive (ir) ANF and the macrophage markers ED1 and S22 or the T-cell marker OX-19 in both thymic sections and in monolayer cultures of thymic cells. In the latter, approximately 17% of the adherent cells stained positive for irANF after 48 h in culture. Of these cells, more than 95% also stained positive for the macrophage marker ED1, whereas approximately 36% of the ED1-positive cells were colocalized with irANF. In contrast, no irANF positive cells were colocalised with the pan-T-cell marker OX-19. In tissue sections, irANF was found in cells distributed predominantly around the cortico medullary junctions and subcapsular areas, with diffuse staining of the cells in the medullary and cortical regions. Sephadex G-50 gel chromatographic profiles of thymic extracts revealed a major peak of immunoreactivity consistent with 15K M(r) and a smaller peak that coeluted with rat ANF-(1-28) of 3K M(r). HPLC analysis of the 3K M(r) species showed a single peak of immunoreactivity, which eluted with a retention time identical to that of synthetic rat ANF-(5 28).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477664 TI - Characterization of a morphine-modulating peptide, FLFQPQRFamide, in the rat hypophysis: biochemical and immunocytochemical studies. AB - The octapeptide FLFQPQRFamide (F8Fa) is a FMRFamide-like peptide with a certain number of antiopiate properties. Previous studies have shown that both F8Fa specific receptors and F8Fa-like material are present in the rat central nervous system. In this study, RIA revealed that the rat neurohypophysis also contains F8Fa immunoreactive (IR) material (230 +/- 49 pg/neural lobe). HPLC profiles revealed several forms of F8Fa IR. Neurohypophysis extracts can also inhibit the binding of F8Fa to rat spinal cord preparations, which suggests that this F8Fa like material has a biological activity. Immunocytochemical observations, at the light and electron microscopic levels, confirmed the presence throughout the neural lobe of F8Fa IR, in axonal fibers and terminals similar to those containing the more classical neurohypophysial hormones. Immunogold staining showed that F8Fa IR was restricted to neurosecretory granules in certain axonal and terminal profiles. Double staining of the same ultrathin sections, using our anti-F8Fa antiserum and vasopressin or its neurophysin specific antibodies, revealed that F8Fa IR was colocalized with vasopressin. F8Fa IR was not visible in ocytocinergic fibers or terminals. A striking depletion of F8Fa IR (80%) was observed in rats which were given 2% saline to drink for 6 days. Similarly, an ip injection of an hypertonic saline solution was shortly followed by a 20% drop of F8Fa IR. In vitro F8Fa IR release from isolated neurohypophysis was evoked under a 56 mM KCl depolarization. These results suggest that F8Fa IR may act as a paracrine/endocrine mediator released from the rat neurohypophysis. PMID- 8477665 TI - Glucoregulatory hormones in the immobilization stress-induced increase of plasma glucose in fasted and fed rats. AB - We investigated 1) the effect of immobilization stress on glucose metabolism in rats after sham operation (SHAM), adrenomedullectomy (ADMX), and adrenalectomy (ADX); and 2) the effect of glucoregulatory hormone infusion on plasma glucose using untreated normal fasted and fed rats under unanesthetized conditions. In immobilization stress, the plasma glucose concentration increased only in the SHAM group during fasting, while under fed conditions, all three groups showed significant increases (SHAM > ADMX > ADX). Plasma glucagon and norepinephrine significantly increased in all groups; plasma epinephrine increased only in the SHAM group, and plasma corticosterone increased in SHAM and ADMX groups under both conditions. The hepatic glycogen content in all fed groups significantly decreased after immobilization stress, while a very low content before stress and an undetectable level after stress were observed in all fasted groups. Only epinephrine infusion increased plasma glucose during fasting, while epinephrine and glucagon infusion increased it under fed conditions. Corticosterone infusion did not change it under either condition. These results suggest that in the fasted condition, only epinephrine plays an essential role, while under fed conditions, glucagon and corticosterone as well as epinephrine also act as synergistic factors in stress-induced hyperglycemia. PMID- 8477666 TI - Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin. AB - For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin. Recent data have demonstrated a role for pituitary activin-B in mediating FSH hypersecretion after ovariectomy (OVX) and during the secondary FSH surge on estrus. Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats. At the termination of all in vivo investigations, rats were killed, trunk blood was collected for determination of serum LH and FSH levels by RIA, and pituitary tissue was collected, pooled (two or three glands per pool), and processed for determination of follistatin messenger RNA (mRNA) levels by a solution-hybridization RNase protection assay. In the first experiment, pituitary follistatin mRNA levels were significantly (P < 0.01) increased 3 weeks after OVX. Treatment of long-term ovariectomized rats with a Nal-Glu LHRH antagonist restored serum LH levels to precastration levels and suppressed serum FSH concentrations by 70%, but follistatin message levels were not altered. In contrast, treatment of castrated rats with recombinant human follistatin-288 selectively suppressed serum FSH levels (50%) and completely abolished OVX induced increases in follistatin mRNA levels. Subsequent experiments revealed that OVX-induced increases in follistatin gene expression could be observed in pituitary tissue grafted underneath the kidney capsule of hypophysectomized rats. Furthermore, follistatin mRNA levels were significantly (P < 0.05) higher in pituitary glands taken from estrous rats during the secondary FSH surge (0200 h) than in glands obtained from rats on proestrous morning when serum FSH levels were basal. Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin. Using cultures of dispersed pituitary cells, addition of recombinant human activin-A for 72 h increased follistatin mRNA levels 3-fold while enhancing only FSH secretion. Collectively, the present results demonstrate a coupling of follistatin gene expression in the anterior pituitary gland with changes in pituitary FSH secretion under conditions where LH secretion is unaltered. Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling. PMID- 8477667 TI - Identification of a Leydig tumor cell protein that is phosphorylated in response to stimulation with choriogonadotropin or epidermal growth factor. AB - Although hCG and mouse epidermal growth factor (mEGF) activate different signaling systems in a clonal strain of murine Leydig tumor cells (designated MA 10), both compounds ultimately elicit several common effects, such as increased steroidogenesis, decreased transcription of the LH/CG receptor gene, and attenuation of adenylyl cyclase. Based on this information, it was hypothesized that hCG and mEGF may induce phosphorylation of a common protein or set of proteins. Studies were performed to identify such a protein if it exists. MA-10 cells were metabolically labeled with [32P]orthophosphate, and phosphorylation patterns were examined and quantitated using two-dimensional gel electrophoresis. A 21-kilodalton protein whose phosphorylation state increased after hCG and mEGF stimulation was identified. Three isoforms of this protein were visible after hCG stimulation, with approximate pI values of 5.9, 6.0, and 6.1, while only two isoforms were visible after mEGF stimulation, with approximate pI values of 6.0 and 6.1. This protein is phosphorylated on serine residues in response to either hCG or mEGF. Since this protein may play a role in eliciting the common actions of hCG and mEGF, its time course of phosphorylation and concentration responsiveness to hCG and mEGF were also characterized. PMID- 8477668 TI - Levels of messenger ribonucleic acid for cytochrome P450 17 alpha-hydroxylase and P450 aromatase in preovulatory bovine follicles decrease after the luteinizing hormone surge. AB - During the transition from the follicular to the luteal phase, follicular steroid secretion shifts from predominantly 17 beta-estradiol and androgen production before the LH surge to decreased androgen and estrogen and increased progesterone production after the LH surge. Our objective was to determine if changes in 17 beta-estradiol and androgen production by the preovulatory follicle are effected via changes in mRNA levels for the steroidogenic enzymes cytochrome P450 17 alpha hydroxylase/C17, C20-lyase (P450-17 alpha) and cytochrome P450 aromatase (P450arom). Heifers were injected with prostaglandin F2 alpha (PGF2 alpha) during the luteal phase to initiate luteolysis and a follicular phase. Preovulatory follicles were obtained at two times before the LH surge, in the early follicular phase (24 h after PGF2 alpha injection) and in the midfollicular phase (48 h after PGF2 alpha), and at one time in the late follicular phase, after the LH surge but before ovulation (20 h after the onset of estrus, about 20 h after the LH surge). Granulosa cells and theca interna were isolated from preovulatory follicles obtained during the early follicular phase and cultured with or without ovine LH (100 ng/ml; n = 4 follicles isolated 24 h after PGF2 alpha). Total RNA extracted from granulosa cells and theca interna, either immediately after cell isolation during the early (n = 5), mid (n = 4)-, or late follicular phase (n = 5) or after 24 or 72 h of culture, was subjected to Northern analysis for P450-17 alpha and P450arom mRNA. Autoradiographs were scanned densitometrically, and values were adjusted for loading and transfer efficiency. P450-17 alpha mRNA was highly abundant in theca interna before the LH surge, but decreased by 96% after the LH surge (P < 0.001). In contrast, P450-17 alpha mRNA in the granulosa cell fraction was very low at all three times of follicle isolation and most likely was due to a slight contamination of the granulosa cell preparation with theca interna. P450arom mRNA was abundant in granulosa cells isolated in the early and midfollicular phase, but decreased by 94% after the LH surge (P < 0.001). In contrast, P450arom mRNA was undetectable in theca interna. Levels of androstenedione and 17 beta-estradiol in follicular fluid were high during the early and midfollicular phase and decreased dramatically after the LH surge (P < 0.05 and P < 0.001, respectively). P450-17 alpha and P450arom mRNA were undetectable after 24 h of culture in the presence or absence of LH and thereafter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477669 TI - Tumor necrosis factor mediates the effects of endotoxin on cholesterol and triglyceride metabolism in mice. AB - The host response to infection is frequently accompanied by changes in cholesterol and triglyceride (TG) metabolism. To determine the role of cytokines in mediating these changes, we studied the effects of endotoxin (LPS), tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1) on cholesterol and TG metabolism in C57Bl/6 (LPS-sensitive) mice and in C3H/HeJ (LPS-resistant) mice whose macrophages do not produce TNF and IL-1 in response to LPS. Sixteen hours after administration, LPS (1 micrograms/mouse) produced a 41% increase in serum cholesterol and a 62% increase in serum TG levels in C57Bl/6 mice whereas a 100 fold higher dose of LPS did not have a significant effect in C3H/HeJ mice. LPS (1 microgram/mouse) also produced a 8.6-fold increase in hepatic cholesterol synthesis and a 2.7-fold increase in hepatic fatty acid synthesis in C57Bl/6 mice but had no effect in C3H/HeJ mice. This suggests that macrophage produced cytokines such as TNF and IL-1 may be involved in mediating these effects of LPS. Additionally, LPS also increased the activity of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. As seen with LPS, TNF and IL-1 also increased serum cholesterol and TG levels in C57Bl/6 mice. Moreover, TNF and IL-1 produced a 2.3- and 2.1-fold increase in hepatic HMG-CoA reductase activity, respectively. Finally, pretreatment of mice with anti-TNF antibodies, but not with an IL-1 receptor antagonist, blocked the effect of LPS on serum cholesterol and TG levels, hepatic cholesterol and fatty acid synthesis, and hepatic HMG-CoA reductase activity. These results suggest that whereas both TNF and IL-1 mimic the effects of LPS on cholesterol and TG metabolism, TNF may be the in vivo mediator of these late effects of LPS in mice. PMID- 8477670 TI - Purification and characterization of a 3,5,3'-L-triiodothyronine-specific binding protein from bullfrog tadpole plasma: a homolog of mammalian transthyretin. AB - We analyzed the nature of the thyroid hormone-binding proteins in bullfrog plasma using N-bromoacetyl-[125I]T3 as an affinity labeling probe. Polyacrylamide gel electrophoresis under nondenaturing conditions of the bullfrog N-bromoacetyl [125I]T3-labeled plasma proteins revealed two proteins with specific binding to T3. A labeled protein that migrated faster than albumin (T-T3BP) was detected only in plasma obtained from tadpoles at stages earlier than, but not at the end of, metamorphic climax. Another protein that migrated more slowly than albumin appeared in the plasma at the late climax stage and was present in the adult stage. To study the function of T-T3BP during metamorphosis, it was purified from tadpole plasma to the single protein. The molecular mass of this protein was estimated to be 56 kilodaltons by gel filtration, but only 16 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which indicates that the molecule comprised four identical subunits. The amino acid composition of T T3BP and the amino acid sequence of its N-terminal portion were highly homologous with those of mammalian transthyretins. These molecular features indicate that T T3BP is a homolog of mammalian transthyretins. However, in contrast to mammalian transthyretins, the affinity of bullfrog transthyretin for T3 was 360 times higher than that for T4. Scatchard analysis revealed that T-T3BP possessed a single class of T3-binding site, with a Kd of 0.67 nM at 0 C. These results suggest that bullfrog transthyretin may play an important role in transporting T3 in the blood during metamorphosis. PMID- 8477671 TI - Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. AB - LH from anterior pituitary and hCG from placenta bind to a common receptor in gonadal and nongonadal reproductive tissues. There have been numerous examples suggesting that the brain may also contain hCG/LH receptors, yet there has been no evidence for their existence so far. We now demonstrate by reverse transcription-nested polymerase chain reaction and northern blotting that the rat brain contains hCG/LH receptor mRNA. A major receptor transcript of 2.6 kilobases and minor transcripts of 1.8 and 4.4 kilobases were found. Western immunoblotting, ligand blotting, and covalent receptor cross-linking studies have shown that rat brain also contains an 80-kilodalton receptor protein that can bind hCG and hLH, but not hFSH. Rat testis used as a positive control showed a higher abundance of multiple transcripts and an 80-kilodalton receptor protein that can bind [125I]hCG. Rat liver used as a negative control did not contain any receptor transcripts or protein. In situ hybridization, dot blotting, immunocytochemistry, and topical autoradiography have revealed that hCG/LH receptors are present in rat hippocampus; dentate gyrus; hypothalamus; cerebellum; choroid plexus; ependymal cells of third, fourth, and lateral ventricles; cortex; brainstem; bovine hypothalamus; and human area postrema. These novel findings could potentially explain numerous previous observations and suggest new possibilities concerning the regulation of brain functions by hCG and LH. PMID- 8477672 TI - Effects of prolonged cycle ergometer exercise on maximal muscle power and oxygen uptake in humans. AB - The mechanical power (Wtot, W.kg-1) developed during ten revolutions of all-out periods of cycle ergometer exercise (4-9 s) was measured every 5-6 min in six subjects from rest or from a baseline of constant aerobic exercise [50%-80% of maximal oxygen uptake (VO2max)] of 20-40 min duration. The oxygen uptake [VO2 (W.kg-1, 1 ml O2 = 20.9 J)] and venous blood lactate concentration ([la]b, mM) were also measured every 15 s and 2 min, respectively. During the first all-out period, Wtot decreased linearly with the intensity of the priming exercise (Wtot = 11.9-0.25.VO2). After the first all-out period (t greater than 5-6 min), and if the exercise intensity was less than 60% VO2max, Wtot, VO2 and [la]b remained constant until the end of the exercise. For exercise intensities greater than 60% VO2max, VO2 and [la]b showed continuous upward drifts and Wtot continued decreasing. Under these conditions, the rate of decrease of Wtot was linearly related to the rate of increase of VO2 [(dWtot/dt) (W.kg-1 x s-1) = 5.0 x 10(-5) 0.20.(VO2/dt) (W.kg-1 x s-1)] and this was linearly related to the rate of increase of [la]b [(dVO2/dt) (W.kg-1 x s-1) = 2.3 x 10(-4) + 5.9 x 10( 5).(d[la]b/dt) (mM.s-1)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477673 TI - Contribution of differentiated ratings of perceived exertion to overall exertion in women while swimming. AB - The purpose of this study was to identify, using multiple regression analysis, the contribution of differentiated ratings of perceived exertion to overall exertion (RPEO) in women while swimming. Ten female subjects swam at submaximal and maximal intensities and the variables measured included oxygen uptake (VO2), heart rate (fc), ventilation (VE), breathing frequency, tidal volume, blood lactate concentration ([la-]b), RPEO, and four differentiated RPE. These four differentiated RPE were cardiac frequency rating (RPEC), respiratory frequency rating (RPER), arm rating (RPE(arm)), and leg rating (RPE(leg)). These variables used the following equation based on VO2 - R = a + c.(S-b)n, where R was the response to increasing exercise intensity (S) and a, b, and c were constants. The exponents (n) of fc, VE and [la-]b were approximately 1.0, 2.0 and 3.3, respectively. The estimated exponents of RPEO, RPEC, RPER, RPE(arm) and RPE(leg) were approximately 2.4, 2.3, 2.2, 2.5 and 2.5, respectively. There was a highly significant relationship between the four differentiated RPE and their associated physiological responses. The results of this study showed that these interrelationships were clearly delineated. As the percentage maximal oxygen uptake (% VO2max) increased, the major contributing factor to RPEO changed. The RPEC was found to be the main contributing factor from 20% to 45% VO2max, but ceased to contribute beyond 50% VO2max. Above 45% VO2max, RPE(arm) was the major influence, and RPER was the secondary influence from 66% to 96% VO2max. The RPE(leg) was the secondary contributing factor only from 27% to 35% VO2max. It was concluded that differentiated RPE contribution was dependent upon the intensity of exercise in women while swimming. PMID- 8477674 TI - Autonomic nervous control of heart rate during blood-flow restricted exercise in man. AB - Power spectra of instantaneous heart rate (fc) allows the estimation of the contribution of sympathetic and parasympathetic control of fc during steady-state conditions. The present study was designed to examine autonomic control of fc as influenced by normal dynamic leg exercise and by ischemic leg exercise. Eight subjects performed supine cycle ergometry at 30% of their control peak work rate, with and without blood-flow restriction. Blood-flow restriction was induced by exposing the exercising legs to a supra-atmospheric pressure of 6.7 kPa (leg positive pressure; LPP). The exercise responses of arterial pressure and fc increased (P < 0.05) by LPP exposure. The exaggerated pressor response may be attributed to a chemoreflex drive originating in the ischemic muscles. Exposure to LPP during exercise also produced a significant decrease in parasympathetically mediated high frequency (HF; 0.15-1.00 Hz) fluctuation of fc, as indicated by a decrease (P < 0.05) in percent HF power compared to the control exercise level. During LPP exercise, the sympathetically mediated very low frequency (VLF; 0-0.05 Hz) fluctuation of fc increased, as indicated by an increase (P < 0.05) in percent VLF power above control exercise levels. Both LPP and control exercise conditions decreased (P < 0.05) power in all frequency ranges of interest compared to their respective resting conditions. The results suggest that the increase in fc associated with normal dynamic exercise was mediated predominantly by parasympathetic withdrawal, whereas the exaggerated fc response during ischemic exercise resulted from a combination of cardiac sympathetic drive and parasympathetic withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477675 TI - Body position affects the power spectrum of heart rate variability during dynamic exercise. AB - The power spectrum analysis of R-R interval variability (RRV) has been estimated by means of an autoregressive method in six men in supine (S) and sitting (C) postures at rest and during steady-state cycle exercise at about 14%, 28%, 45%, 67% of the maximal oxygen consumption (% VO2max). The total power of RRV decreased exponentially as a function of exercise intensity in a similar way in both postures. Three components were recognized in the power spectra: firstly, a high frequency peak (HF), an expression of respiratory arrhythmia, the central frequency (fcentral) of which increased in both S and C from a resting value of about 0.26 Hz to 0.42 Hz at 67% VO2max; secondly, a low frequency peak (LF) related to arterial pressure control, the fcentral of which remained constant at 0.1 Hz in C, whereas in S above 28% VO2max decreased to 0.07 Hz; and thirdly, a very low frequency component (VLF; less than 0.05 Hz, no fcentral). The power of the three components (as a percentage of the total power) depended on the body posture and the metabolic demand. HF% at rest was 30.3 (SEM 6.6) % in S and 5.0 (SEM 0.8) % in C. During exercise HF% decreased by about 30% in S and increased to 19.7 (SEM 5.5) % at 28% VO2max in C. LF% was lower in S than in C at rest [31.6 (SEM 5.7) % vs 44.9 (SEM 6.4) %; P < 0.05], remaining constant up to 28% VO2max.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477676 TI - Differences in activation patterns in elbow flexor muscles during isometric, concentric and eccentric contractions. AB - To investigate the relative activation of the synergistic muscles during three different types of muscle contraction, the electromyograms (EMG) of two elbow flexor muscles, the biceps brachii (BB) and the brachioradialis (BR), have been compared. To accomplish this eight healthy human subjects performed the following elbow flexions against the same load--concentric, eccentric and isometric contractions. The isometric contractions were performed at three elbow angles: 10, 45 and 90 degrees (0 degree equal to full extension). The EMG were recorded by bipolar surface electrodes, and the relative activation between the two muscles was evaluated as the quotient of mean EMG activities (BR/BB). For the isotonic elbow flexions, BR/BB were calculated at three angle divisions: 0-30 degrees, 30-60 degrees and 60-90 degrees. Results indicated that the relative activation of the BR during the concentric contractions was higher than that of the eccentric contraction, particularly at the extended elbow angles, i.e. the BR/BB of the concentric contractions for the elbow joint angles ranging from 0-30 degrees and 30-60 degrees were significantly greater (P < 0.05) than those of the eccentric contractions. During the isometric and eccentric contractions, the BR/BB at the flexed joint angles tended to be greater than those at the extended angles. In contrast, there were no angle-dependent BR/BB variations during the concentric elbow flexions. Further, changing patterns in the EMG power spectra due to the type of contraction were different between BB and BR. These results indicated that the activation pattern in the two elbow flexor muscles varied with the muscle contraction pattern. PMID- 8477677 TI - The effect of ski training at altitude and racing on pituitary, adrenal and testicular function in men. AB - The effect of similar prolonged exercise on hormonal changes was studied at sea level and at moderate altitude. Four cross-country skiers participated in a 30-km race and five biathlonists in a 20-km race at sea level in Finland and during altitude training and racing at 1650 m in Les Saisies, France. Venous blood samples were taken at both altitudes before the race between 0800 and 0900 hours and 25-35 min after the race. Resting blood samples were also taken before and after the altitude training and the period of racing. Serum testosterone concentration was higher before the race at altitude than at sea level (19%, P < 0.02), and 30 min after the race growth hormone (GH) concentration was higher at sea level than at moderate altitude (P < 0.002). There were not significant differences in serum luteinising hormone between the altitudes. Serum cortisol concentration was higher after the altitude training and the period of racing than before (P < 0.02) but no difference was observed in testosterone. We concluded, that since the profiles of the anabolic-catabolic hormone concentrations measured are indicators of the performance level of athletes, our data indicated that to follow them during altitude training could be beneficial in optimizing training programme for individual athletes. We also concluded, that the lower GH concentration after racing at moderate altitude may have been a consequence of decreased racing speed and/or increased physical performance. PMID- 8477678 TI - Repeated normoxic hyperbaric exposures induce haemodynamic and myocardial changes in rats. AB - The effect of repeated exposure to ambient pressures of 5 bar (500 kPa), in atmospheres comprising normal partial pressures of oxygen [0.2 bar (20 kPa)] and nitrogen [0.8 bar (80 kPa)] and 4 bar (400 kPa) helium, on cardiac function and morphology was assessed in conscious rats. Ten test rats underwent chamber dives daily for 40 consecutive days, and ten control rats were exposed in the same chamber for an equal period of time, but in air at 1 bar (100 kPa). Cardiac output (Qc) and myocardial blood flow (Qmyocardial) were determined by the microsphere method. After 40 days, the body mass was 7% greater in the control than in the test rats (P < 0.05), although they were given exactly the same amount of standard food. The test rats had a significantly higher (7% absolute, 12% ventricular mass to body mass, P < 0.05) heart mass (left ventricular myocardium, including the ventricular septum) than the control rats. The percentage tissue dry mass of the right and left ventricles was equal in the two groups. Microscopic examination revealed a number of small focal necroses in the left ventricle of the test rats but none in the control rats. The left ventricular pressure (LVP) and the maximum velocity of LVP increase (contractility) and decrease were significantly increased (25%-96%, P < 0.001) in the pre-exposed compared to the control rats at 1 bar (100 kPa). The systolic arterial pressure, heart rate and respiratory frequency were similar in the two groups at 1 bar (100 kPa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477679 TI - Elbow flexion strength curves in untrained men and women and male bodybuilders. AB - The influence of elbow joint angle on voluntary isometric elbow flexion strength was assessed in 15 young women (F), 18 young men (M) and 11 male bodybuilders (BB). Measurements were made at elbow joint angles of 1.31, 1.57, 1.83, 2.09, 2.36, 2.62 and 2.88 rad (3.14 rad = 180 degrees = full extension). The peak voluntary strength [mean (SE), N.m] in M [69.5 (4.3)] and BB [93.3 (4.8)] occurred at 2.09 rad (120 degrees), but occurred at 1.57 rad (90 degrees) in F [35.4 (2.4)]. Peak torque at 1.31 rad was 20% and 25% lower than at 2.09 rad in M and BB, respectively, but did not differ between these two angles in F. The larger elbow flexor muscle and fibre size in M and BB may have been responsible for their impaired torque production at joint angles corresponding to the shortest muscle lengths. PMID- 8477680 TI - Elbow flexor evoked twitch contractile properties in untrained men and women and male bodybuilders. AB - The influence of elbow joint angle on elbow flexor isometric evoked twitch contractile properties was assessed in 15 young women (F), 18 young men (M) and 11 male bodybuilders (BB). Measurements were made at elbow joint angles of 1.31, 1.57, 1.83, 2.09, 2.36, 2.62 and 2.88 rad (3.14 rad = 180 degrees = full extension). The largest peak twitch torque values [mean (SE) N.m] in F [3.77 (0.20)], M [10.38 (0.68)] and BB [11.38 (1.05)] occurred at 2.88 rad. Peak torque was progressively smaller at smaller joint angles, but the decline from 2.88 to 1.31 rad was greater in M (68%) and BB (76%) than F (59%). Thus, the magnitude of intergroup differences in peak twitch torque (PT) was joint angle dependent. Twitch time to peak torque (TPT) was influenced in a complex way by joint angle in the three groups; BB had the lowest values at small joint angles but the highest values at the largest angles. Half-relaxation time (HRT) generally increased from the smallest to largest joint angles in a pattern that did not differ significantly among the three groups. Maximum rates of twitch torque development and relaxation showed the same pattern of results as PT, indicating that these time-related measures were more sensitive to joint angle effects on PT than on TPT or HRT. The results of this study indicate that careful consideration should be given to the selection of joint angles in the measurement of evoked twitch contractile properties for the purpose of making group comparisons or investigating the effects of interventions such as training. PMID- 8477681 TI - Vibration aftereffects on vasoconstrictor response to cold in the normal finger. AB - The acute effects of unilateral 30 min exposure to hand-arm vibration on the vasoconstrictor response to cold in a finger from both hands were investigated in 12 healthy men (age 18-38 years) who had never worked with vibrating tools. One hand was exposed to accelerations of 4.0 and 16.0 m.s-2 on 2 different days. The vasoconstrictor response to cold (R%) was expressed as the relative decrease in finger systolic blood pressure, measured using cuff and strain gauge techniques, when the finger was cooled from 30 to 10 degrees C. The R% of both third fingers were measured simultaneously before unilateral vibration exposure and 15, 60 and 120 min after the end of each exposure. The R% of both fingers were not affected by the low acceleration vibration (P > 0.10). Exposure to the high acceleration vibration was followed by an unchanged R% of the exposed finger but an increased R% of the non-exposed finger after 15 min (P < 0.05); there was an equal increase of 30%-40% in R% of both fingers after 60 min (P < 0.05). The R% of both fingers had returned to normal after 120 min (P > 0.10). The results would indicate that short-term exposure to vibration induces a transitory hyperreactive central vasoconstrictor drive to the central sympathetic nervous system or circulating agents, which initially was locally counteracted by an induced hyporeactive vasoconstrictor function of local vasomotor mechanisms of the vibration exposed digital arteries. The hyperreactive vasoconstrictor effect demonstrated may contribute to the development of vibration-induced white finger if cumulative exposure time were to be considerably increased. PMID- 8477682 TI - Respiratory changes and structure of sleep in young high-altitude dwellers in the Andes of Peru. AB - Sleep organisation in eight young [mean (SD); 20.9 (2.6) years] Peruvian high altitude residents was studied in a laboratory in Cerro de Pasco at 4300 m. Electroencephalograms, electromyograms, electro-oculograms, electrocardiograms, respiratory movements and arterial oxygen saturation were recorded on an 8 channel Medilog recorder and analysed later in England. Haematocrits ranged from 48% to 64% [57.9 (5.6)%]. The amount of slow wave rapid eye movement (REM) sleep was similar to that reported in young lowlanders sleeping at sea level but very different to the disturbed sleep in visitors sleeping at high altitude. All the Peruvians showed episodes of periodic breathing and respiratory apnoeas [29 (15) night-1] resulting in marked arterial oxygen desaturation [81 (4.5)%; changes of 6 (2.5)%]. These events occurred either during stage 2 or REM sleep and were more frequent in those with lower haematocrits. The amount of wakefulness during the night was 2-3 times greater than would be expected in an age-matched lowland population at sea level. The awakenings were strongly associated with apnoeas (P < 0.02) but were negatively correlated with haematocrit, although this was only significant for seven of the subjects (P < 0.05). PMID- 8477683 TI - Gender differences in strength and muscle fiber characteristics. AB - Strength and muscle characteristics were examined in biceps brachii and vastus lateralis of eight men and eight women. Measurements included motor unit number, size and activation and voluntary strength of the elbow flexors and knee extensors. Fiber areas and type were determined from needle biopsies and muscle areas by computerized tomographical scanning. The women were approximately 52% and 66% as strong as the men in the upper and lower body respectively. The men were also stronger relative to lean body mass. A significant correlation was found between strength and muscle cross-sectional area (CSA; P < or = 0.05). The women had 45, 41, 30 and 25% smaller muscle CSAs for the biceps brachii, total elbow flexors, vastus lateralis and total knee extensors respectively. The men had significantly larger type I fiber areas (4597 vs 3483 microns2) and mean fiber areas (6632 vs 3963 microns2) than the women in biceps brachii and significantly larger type II fiber areas (7700 vs 4040 microns2) and mean fiber areas (7070 vs 4290 microns2) in vastus lateralis. No significant gender difference was found in the strength to CSA ratio for elbow flexion or knee extension, in biceps fiber number (180,620 in men vs 156,872 in women), muscle area to fiber area ratio in the vastus lateralis 451,468 vs 465,007) or any motor unit characteristics. Data suggest that the greater strength of the men was due primarily to larger fibers. The greater gender difference in upper body strength can probably be attributed to the fact that women tend to have a lower proportion of their lean tissue distributed in the upper body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477684 TI - Strength training alters contractile properties of the triceps brachii in men aged 65-78 years. AB - Voluntary and electrically evoked contractile properties were studied in the triceps brachii following a 24-week dynamic strength training program in ten men aged 65-78 years. Eight men of a similar age were control subjects. A resistance overload program was undertaken three times per week with subjects performing four sets of six to eight repetitions at 80% of their one repetition on maximum (1RM). Maximum voluntary contraction (MVC) and contractile properties were measured at 0, 12, and 24 weeks in the exercise group and at 0 and 24 weeks in the controls. The 1RM was used to assess dynamic strength at 0 and 24 weeks in the exercise group. Contractile measures consisted of supramaximal isometric twitch and post-activation twitch parameters. Muscle size was estimated from anthropometric measurements. Compared with the control group, the exercise group MVC increased by about 20% and time to peak tension was slowed by about 11%. Also in the exercise group the peak rate of torque development of the potentiated twitch was reduced by about 10%. Twitch potentiation was substantial in both groups (about 140%) and unaffected by training. The 1 RM increased by about 30%, and there was a non-significant positive change of 8.6% in the muscle plus bone cross-sectional area in the exercise group. The results show that the force generating capacity of the triceps brachii in these men can be significantly improved for up to 24 weeks using concentric overload training. Furthermore, the finding of slowed twitch properties and no change in peak twitch amplitude substantiate and extend the limited data currently available on intrinsic contractile changes in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477685 TI - Maximal heart rates and plasma lactate concentrations observed in middle-aged men and women during a maximal cycle ergometer test. AB - The purpose of this study was to investigate criteria for maximal effort in middle-aged men and women undertaking a maximal exercise test until they were exhausted if no measurements of oxygen uptake are made. A large group of 2164 men and 975 women, all active in sports and aged between 40 and 65 years, volunteered for a medical examination including a progressive exercise test to exhaustion on a cycle ergometer. In the 3rd min of recovery a venous blood sample was taken to determine the plasma lactate concentration ([la-]p,3 min). Lactate concentration and maximal heart rate (fc,max) were lower in the women than in the men (P < 0.001). Multiple regression analyses were performed to assess the contribution of sex to [la-]p,3 min, independent of age and fc,max. It was found that [la-]p,3 min was about 2.5 mmol.l-1 lower in women than in men of the same age and fc,max. In our population 88% of the men and 85% of the women met a combination of the following fc,max and [la-]p,3 min criteria: fc,max equal to or greater than 220 minus age beats.min-1 and/or [la-]p,3 min equal to or greater than 8 mmol.l-1 in the men and fc,max equal to or greater than 220 minus age beats.min-1 and/or [la ]p,3 min equal to or greater than 5.5 mmol.l-1 in the women. PMID- 8477686 TI - Effect of one- and two-leg training on arm and two-leg maximum aerobic power. AB - The purpose of this study was to examine the effect of one- and two-leg training on arm and two-leg maximum aerobic power. Seven subjects cycle-trained both legs simultaneously for 30 min.day-1, 4 days.week-1 for 4 weeks. Nine subjects cycle trained each leg 15 min.day-1, 4 days.week-1 for 4 weeks. Both groups trained at a heart rate equal to that measured at 75% of their two-leg maximum aerobic power. Thus, during each training session the groups performed 30 min of work at the same heart rate intensity. Five subjects served as a non-training control group. Arm and leg maximum oxygen uptake tests were conducted before and after training. Only two-leg training induced significant gains in arm aerobic power (P < 0.0003), whereas both modes of training resulted in significant increases in two-leg aerobic power (P < 0.0008). The data demonstrate that improvements in arm aerobic power were dependent on the quantity of leg muscle mass involved in the training, whereas gains in two-leg aerobic power occurred regardless of whether the legs were trained separately or simultaneously. PMID- 8477687 TI - Ascidian entactin/nidogen. Implication of evolution by shuffling two kinds of cysteine-rich motifs. AB - Entactin/nidogen, a major component of the basement membrane, has a domain structure comprising three globular domains, and thread-like and rod-like domains connecting them. It contains six epidermal-growth-factor-(EGF)-like motifs and one thyroglobulin-like motif. In the present study, ascidian entactin/nidogen has been identified by a monoclonal antibody technique. We prepared anti-(ascidian entactin/nidogen)IgG, named anti-AsEnt1, then cloned the cDNA of ascidian entactin/nidogen using anti-AsEnt1 as a probe, and determined its entire sequence. Mainly because the deduced amino acid sequence exhibited high similarity to mouse entactin and human nidogen, and because the antigen localized in basement membrane of ascidian body-wall muscle, we have concluded that the antigen anti-AsEnt1 corresponds to the ascidian entactin/nidogen homologue. The deduced amino acid sequence of ascidian entactin/nidogen clearly showed that the ascidian homologue also has a domain structure. However, the ascidian homologue lacked the thread-like domain, and the rod-like domain differed from that of mouse entactin in composition, consisting of two kinds of cysteine-rich motifs, that is, the EGF-like motif and the thyroglobulin-like motif. These results suggest that entactin/nidogen have evolved by modifying the domains, especially by shuffling the two kinds of cysteine-rich motifs. PMID- 8477688 TI - Characterization of the promoter region of the rat hepatocyte-growth factor/scatter-factor gene. AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen for hepatocytes in primary culture. In response to liver damage, the levels of HGF/SF mRNA change in various tissues. In this study, we isolated a genomic DNA fragment containing the promoter region of the rat HGF/SF gene and analyzed transcription initiation sites and their utilization in response to acute liver injury. Rat HGF/SF-mRNA synthesis starts from at least three sites in the liver, spleen and kidney. One of these sites is preferentially utilized in the liver and spleen in response to acute liver injury. In the 5' flanking region, several cytokine related sequence elements that might be involved in the regulation of HGF/SF-gene expression are located near the transcription-initiation sites. The effects of cytokines related to these sequence elements on the production of HGF/SF mRNA were examined using a cell culture system. Transforming growth factor-beta 1 (TGF beta 1) inhibits the production of HGF/SF mRNA by Shay granulocytic sarcoma derived cells. The TGF-beta 1-inhibitory element, one of the sequence elements present in the promoter sequence, may mediate the inhibition of HGF/SF-gene expression by TGF-beta 1. PMID- 8477689 TI - Cloning and structural analysis of alpha-latroinsectotoxin cDNA. Abundance of ankyrin-like repeats. AB - alpha-Latroinsectotoxin (alpha-LIT), purified from venom glands of the black widow spider Latrodectus mactans tredecimguttatus, is a presynaptic neurotoxin selective only for insects. A cDNA encoding the putative alpha-LIT precursor was isolated from a spider venom gland cDNA library. The cDNA contains a 4236-base pair open reading frame corresponding to a 157826-Da protein composed of 1411 amino acids. The mature alpha-LIT, with molecular mass approximately 130 kDa, is probably derived from double processing in the N-terminal and C-terminal regions of the primary translation product. The structure region, extending over residues 464-1176, is composed almost entirely of ankyrin-like repeats which represent a motif also found in the alpha-latrotoxin (alpha-LTX), which has selective action on vertebrates. Total alignment of the alpha-LIT and alpha-LTX amino acid sequences reveals an overall similarity of 34.1%. Strong sequence divergence is observed in analogous cysteine-rich regions situated within the ankyrin-repeat domains of both alpha-LIT and alpha-LTX. PMID- 8477690 TI - 8-Dimethylamino-1-methyladenine, a novel potent antagonist of the 1-methyladenine receptor in starfish oocytes. AB - Starfish oocytes are naturally arrested in the late G2 phase of the first meiotic division. The follicle-cell-derived hormone, 1-methyladenine, is responsible for highly synchroneous induction of oocyte maturation. A series of systematically modified 1-methyladenine analogues was used to map the essential molecular interactions between 1-methyladenine and its stereospecific receptors, which are localized on the oocyte plasma membrane. The earlier hypothesis about structure/activity relationships has been confirmed. Quantum-chemical calculations indicated additional dipole-dipole interactions and presumably a charge-transfer interaction, with the nucleobase as pi-electron donor. Among the 49 compounds tested, a series of novel inhibitors of 1-methyladenine-induced maturation was found. With the synthesis of 8-dimethylamino-1-methyladenine (concentration for 50% inhibition 1 microM), a very potent antagonist of the natural hormone was obtained which may become an important tool for investigating the mechanism of 1-methyladenine-induced maturation of the starfish oocytes, an important model for cell-cycle-control studies. The results are discussed in the context of preexisting biological data. In conclusion, we propose a modified model of the molecular interactions between 1-methyladenine and its receptor. PMID- 8477691 TI - Homonuclear and heteronuclear NMR studies of oxidized Desulfovibrio vulgaris flavodoxin. Sequential assignments and identification of secondary structure elements. AB - Recombinant Desulfovibrio vulgaris flavodoxin (molecular mass 16.3 kDa) was produced in Escherichia coli. The oxidized protein has been investigated with a combination of homonuclear and heteronuclear two-dimensional and heteronuclear three-dimensional NMR spectroscopy. Sequence-specific assignment of all backbone and most of the side chain 1H and 15N resonances has been obtained. The secondary structure has been inferred from the pattern of sequential, medium-, and long range NOEs, together with information about slowly exchanging amide hydrogens and HN-H alpha spin-spin coupling constants. In solution, flavodoxin consists of a five-stranded parallel beta-sheet and four alpha-helices. Residues 3-9, 32-36, 52 58, 87-96, and 123-128 are involved in the beta-sheet whereas the a-helical regions comprise residues 13-28, 69-76, 104-114, and 134-148. Several proton resonances of the bound flavin mononucleotide cofactor have been assigned. NOE contacts between the prosthetic group and the apoprotein have been detected. PMID- 8477692 TI - Chymotryptic cleavage of lipoprotein lipase. Identification of cleavage sites and functional studies of the truncated molecule. AB - Treatment of bovine lipoprotein lipase (LPL) with chymotrypsin results in cleavage between residues Phe390-Ser391 and between Trp392-Ser393, indicating that this region is exposed in the native conformation of LPL. Two main fragments are generated, one large including the amino-terminus (chymotrypsin-truncated LPL = c-LPL) and one small, carboxy-terminal fragment. The small fragment is not stable, but is further degraded by the protease. Isolated c-LPL has full catalytic activity against tributyryl glycerol (tributyrin) and p-nitrophenyl butyrate, while the activity against emulsions of long-chain triacylglycerols and against liposomes is reduced and the activity against milk fat globules and chylomicrons is lost. Several properties of c-LPL were investigated. It was found that c-LPL interacts with apolipoprotein CII (apo CII) as efficiently as intact LPL. The truncated enzyme bound to liposomes and to emulsions of long-chain triacylglycerols as well as the intact enzyme did. In contrast, c-LPL did not bind to milk fat globules or to chylomicrons. The activity of c-LPL was more sensitive to inhibition by other lipid-binding proteins, e.g. apolipoprotein CIII (apo CIII), than was the intact enzyme. The affinity for heparin was as high with c-LPL as with intact LPL. Like intact LPL, c-LPL is dimeric in its active form, as evidenced by sucrose density gradient centrifugation. It is concluded that the reduced catalytic and lipid-binding properties of c-LPL compared with intact LPL are related to the properties of the substrate interface. It is speculated that the carboxy-terminal part of LPL contains a secondary lipid-binding site, which is important for activity against chylomicrons and related substrates. PMID- 8477693 TI - A Candida albicans homolog of CDC25 is functional in Saccharomyces cerevisiae. AB - We have cloned, by functional complementation of the cdc25-2 mutation of Saccharomyces cerevisiae, a homolog of CDC25 from the pathogenic yeast Candida albicans. The new gene, named CSC25 codes for a 1333-amino-acid protein. The full length gene, as well as a truncated form coding for 795 amino acids, suppresses the thermosensitive phenotype of cdc25ts mutants. Biochemical analysis has shown that Csc25 activates the Ras/adenylyl cyclase pathway in S. cerevisiae at a rate two to three times faster than Cdc25, under the same conditions. The C-terminal domain of Csc25 is highly similar to the C-terminal domain of Cdc25, to almost the same extent as the C-terminus of the endogenous Cdc25 homolog Sdc25. We show that polyclonal anti-Cdc25 antibodies interact with Csc25 expressed in S. cerevisiae. In addition to the full length protein (approximately 150 kDa), we have found a approximately 50-kDa polypeptide which seems to include the C terminus of the CSC25 gene product. PMID- 8477694 TI - IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Corrections to recommendations 1983. PMID- 8477695 TI - Involvement of the 20S proteasome in the degradation of ornithine decarboxylase. AB - Eukaryotic cells have been shown to contain two high-molecular-mass proteases of 700 kDa and 1400 kDa (20S and 26S proteases, respectively). It has been suggested that the 20S protease, also known as proteasome, may constitute the catalytic core of the 26S protease. While the role of the free 20S protease in intracellular protein degradation is unclear, the 26S protease is implicated in the degradation of ubiquinated proteins. We have recently demonstrated, that ornithine decarboxylase (ODC), one of the most labile proteins in mammalian cells, is degraded via an ATP-dependent but ubiquitin-independent proteolytic pathway. Here we extend these observations by demonstrating that in reticulocyte lysate ODC degradation is inhibited by antibodies raised against the C9 subunit of rat proteasome. Partial fractionation of the lysate demonstrated preferential degradation of ODC in the fraction of the lysate proteins that are precipitated by 38% ammonium sulfate. Since it was demonstrated that the 26S protease precipitates at this concentration of ammonium sulfate while the 20S proteasome remains soluble, our results suggest that the 26S protease is the one degrading ODC. PMID- 8477696 TI - Purification and characterization of cytochrome P450RR1 from Rhodococcus rhodochrous. AB - A soluble cytochrome P450 whose synthesis is induced by and that binds 2 ethoxyphenol was purified to apparent homogeneity from Rhodococcus rhodochrous strain 116. The enzyme had a subunit molecular mass of 44.5 kDa as determined by SDS/PAGE and a pI of 5.2. The electronic absorption spectrum indicates that the native cytochrome in the absence of substrate is predominantly in the low-spin state (13% high-spin state in 50 mM Mops, pH 7.0 25 degrees C). 2-Methoxyphenol binds to the cytochrome with a macroscopic dissociation constant of 0.53 +/- 0.03 microM (50 mM Mops, pH 7.0, 25 degrees C) and induces a 99.7% transition of the heme iron to the pentacoordinate high-spin form. Using a reconstituted in-vitro activity assay, it was demonstrated that P450RR1 catalyzed the O-dealkylation of 2-ethoxyphenol and 2-methoxyphenol to produce catechol. The cytochrome binds other ortho-substituted phenols, including 2-ethoxyphenol, 2-methylphenol (o cresol) and 2-chlorophenol. The affinity of P450RR1 for these compounds is lower than that of 2-methoxyphenol and they are less effective than 2-methoxyphenol at inducing a transition in the heme iron to the high-spin state. Para-substituted and meta-substituted ether phenols did not induce a spin transition. PMID- 8477697 TI - Human-liver cytochromes P-450 expressed in yeast as tools for reactive-metabolite formation studies. Oxidative activation of tienilic acid by cytochromes P-450 2C9 and 2C10. AB - Human liver cytochromes P-450 (P450) 2C9 and 2C10 expressed in yeast reproduce all the metabolic features of the oxidation of tienilic acid (2-aryloxo thiophene) and its isomer (3-aroylthiophene) by human liver microsomes. Microsomes of yeast expressing either P450 2C9 or P450 2C10 catalyze (a) the 5 hydroxylation of tienilic acid by NADPH and O2 (Km = 6 microM, Vmax = 2.5 turnover/min), (b) the activation of tienilic acid and its isomer into electrophilic metabolites which covalently bind to proteins, and (c) the formation of a mercaptoethanol adduct which results from the trapping of the tienilic acid isomer sulfoxide by this thiol. Microsomes of yeast expressing human liver P450 3A4, 1A1 and 1A2 are unable to catalyze these reactions. There is a striking similarity between the quantitative characteristics of the oxidation of tienilic acid (and its isomer) by yeast-expressed P450 2C9 (or 2C10) and by human liver microsomes: (a) analogous Km values (around 10 microM) for tienilic acid 5-hydroxylation, (b) a strong inhibition of tienilic acid oxidation by human sera containing anti-(liver kidney microsomes type 2) (anti-LKM2) antibodies, and (c) almost identical relative ratios of tienilic acid metabolic activation/5-hydroxylation and of tienilic acid activation/the activation of its isomer with both systems. Rates of oxidation of tienilic acid (and its isomer) by yeast microsomes are 6-8 fold higher than those found in human liver microsomes, which would be in agreement with the previously reported amount of P450 2C9 in human liver. These results not only suggest the important role of P450 2C9 in the oxidative metabolism of tienilic acid in human liver, but also indicate that the 5-hydroxylation reaction could be a useful marker for P450 2C9 activity and underline the interest of human liver P450s expressed in yeast as tools for studying the formation of reactive metabolites. PMID- 8477698 TI - Molecular cloning, developmental pattern and tissue expression of 3-hydroxy-3 methylglutaryl coenzyme A reductase of the cockroach Blattella germanica. AB - In insects, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) synthesizes mevalonate for the production of nonsterol isoprenoids, which are essential for growth and differentiation. To understand the regulation and developmental role of HMG-CoA reductase, we have cloned a full-length HMG-CoA reductase cDNA from the cockroach Blattella germanica. This cDNA clone was isolated using as a probe a partial cDNA of B. germanica HMG-CoA reductase, amplified using the polymerase chain reaction. The composite 3433-bp cDNA sequence contains an open reading frame encoding a polypeptide of 856 amino acids (Mr, 93165). The C-terminal region is more similar to hamster HMG-CoA reductase than is the Drosophila melanogaster enzyme (79% and 69% conserved residues, respectively), and the potential transmembrane domains at the N-terminal region are structurally conservative with both enzymes. The C-terminal region of the B. germanica protein has been expressed as a fusion protein in Escherichia coli and exhibits HMG-CoA reductase activity. Analysis of B. germanica HMG-CoA reductase mRNA levels, reveals a 3.6-kb transcript, that is overexpressed in 4-day-old embryos. Northern blot analysis of RNA samples from different adult female tissues shows high HMG CoA reductase mRNA levels in the ovary and lower levels in brain and muscle. PMID- 8477699 TI - Oxygenation of lipoproteins by mammalian lipoxygenases. AB - Oxidative modification converts low-density lipoprotein (LDL) into its atherogenic form and appears to be a necessary precondition for LDL uptake by macrophages during foam cell formation. Cellular lipoxygenases have been implicated in this process. We studied the interaction of purified mammalian lipoxygenases with human LDL in vitro and found that the arachidonate 15 lipoxygenases of rabbit and man are capable of oxygenating lipoproteins as indicated by oxygen uptake and by the formation of thiobarbituric-acid-reactive substances. Furthermore, oxygenated polyenoic fatty acids, such as 13 hydro(pero)xy-9Z,11E-octadecadienoic acid and 15-hydro(pero)xy-5,8,11,13(Z,Z,Z,E) eicosatetraenoic acid were detected in the lipid compartment of various lipoproteins classes after lipoxygenase treatment. More than 90% of the oxygenated polyenoic fatty acids were found in the ester-lipid fraction, particularly in the cholesterol esters, whereas only small amounts of free hydro(pero)xy polyenoic fatty acids were detected. Lipoxygenase-catalyzed oxygenation of LDL is not restricted to the lipid compartment but also leads to a cooxidative modification of the apoproteins as indicated by changes in the electrophoretic mobility and by the formation of carbonyl derivatives of amino acid side chains. The possible biological significance of lipoxygenase-induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed. PMID- 8477700 TI - Intracellular retention and degradation of human mutant variant of a alpha 1 antitrypsin in stably transfected Chinese hamster ovary cell lines. AB - Normal (PiM) and mutant (PiZ) variants of human alpha 1-antitrypsin (alpha 1-AT) cDNA, cloned into the pTnd eucaryotic expression vector, were used to derive recombinant Chinese hamster ovary cell lines permanently expressing the corresponding proteins. Secretion, accumulation and glycosylation of PiM and PiZ alpha 1-AT proteins were studied in the presence of various transport-impairing drugs. Pulse-chase, followed by immunoprecipitation as well as immunofluorescence experiments showed that the PiZ alpha 1-AT undergoes continuous degradation that was prevented by Brefeldin A but not by incubation of cells at 16 degrees C. Moreover, monensin partially impaired the glycosylation of both PiM and PiZ alpha 1-AT but not their secretion nor the degradation of PiZ alpha 1-AT. Those results suggest that PiZ alpha 1-AT degradation occurs in the cis-Golgi network, a compartment located between the endoplasmic reticulum and the Golgi stack. The process did not apparently involve lysosomes since it was insensitive to chloroquine. In addition, inhibition of PiM and PiZ alpha 1-AT glycosylation and secretion by tunicamycin did not result in the accumulation of the protein, but instead in its rapid lag-free degradation. Treatment of cells with the A23187 ionophore, for a short (60 min) but not a long (24 h) period, improved the secretion of PiZ alpha 1-AT in a similar way as it affects retention of naturally endoplasmic-reticulum-resident proteins, suggesting that the small proportion of PiZ alpha 1-AT which is not degraded or secreted, but accumulates in the endoplasmic reticulum, is back transported as a partially glycosylated species from the post endoplasmic reticulum compartment in which degradation takes place. PMID- 8477701 TI - Purification and characterization of an extremely thermostable beta-glucosidase from the hyperthermophilic archaeon Pyrococcus furiosus. AB - Cell-free extracts of cellobiose-grown cells of the hyperthermophile Pyrococcus furiosus contain very high activities (19.8 U/mg) of a beta-glucosidase. The cytoplasmic enzyme was purified 22-fold to apparent homogeneity, indicating that the enzyme comprises nearly 5% of the total cell protein. The native beta glucosidase has a molecular mass of 230 +/- 20 kDa, composed of 58 +/- 2-kDa subunits. The enzyme has a pI of 4.40. Thiol groups are not essential for activity, nor is the enzyme dependent on divalent cations or a high ionic strength. The enzyme shows optimum activity at pH 5.0 and 102-105 degrees C. From Lineweaver-Burk plots, Vmax values of 470 U/mg and 700 U/mg were found for cellobiose (Km = 20 mM) and p-nitrophenyl-beta-D-glucopyranoside (Km = 0.15 mM), respectively. The purified enzyme also exhibits high beta-galactosidase activity and beta-xylosidase activity, but shows no activity towards alpha-linked disaccharides or beta-linked polymers, like cellulose. The purified beta glucosidase shows a remarkable thermostability with a half life of 85 h at 100 degrees C and 13 h at 110 degrees C. PMID- 8477702 TI - Isozyme developments in mammalian class-I alcohol dehydrogenase. cDNA cloning, functional correlations, and lack of evidence for genetic isozymes in rabbit. AB - Isozyme patterns differ widely among the classical type (class I) of mammalian alcohol dehydrogenases. For the rabbit enzyme, the possibility of isozymes has been reported but structural evidence is lacking. This system was now studied at both the mRNA/cDNA and protein levels. Ten cDNA clones, coding for class-I alcohol dehydrogenase, were isolated from a rabbit liver cDNA library using a human DNA fragment as probe. The cDNA spanned 1296 bp, including the entire coding region. All clones coded for the same polypeptide and Northern blots identified a single mRNA corresponding to about 1.5 kb. Comparison of two protein forms (CC and BC) by HPLC peptide fingerprinting and structural analysis revealed peptide segments identical in amino acid sequence. Consequently, direct protein analyses and Northern blots show the presence of only one primary translation product. The data suggest that lagomorphic alcohol dehydrogenase, like the rodent enzyme, is not as isozyme rich as it may appear superficially, and that secondary modifications contribute substantially to mammalian alcohol dehydrogenase multiplicity. The active center of the rabbit enzyme suggests similarities to the horse S, human gamma, and rat enzyme structures, compatible with a steroid dehydrogenase activity shown experimentally. Typical class-I properties were established by direct analysis and confirmed by structural properties (Km for cyclohexanol 0.8-1.1 mM, for ethanol 1.6-1.9 mM). The isozyme versus species differences mark the variability of class-I alcohol dehydrogenase versus class III and suggest a parallelism between rapid mutational differences and frequent duplicatory events. PMID- 8477703 TI - 1H-NMR spectroscopy of beta B2-crystallin from bovine eye lens. Conformation of the N- and C-terminal extensions. AB - 1H-NMR spectroscopic studies of a 46-kDa homodimer, beta B2-crystallin, from bovine eye lens are presented. beta B2-crystallin has terminal extensions extending from globular N- and C-terminal domains that are well resolved in the NMR spectra, whereas, in the main, resonances from the bulk of the protein are not observed. Using two-dimensional NMR methods on beta B2-crystallin, its synthesised terminal extensions and a proteolysed sample of beta B2-crystallin with a portion of its C-terminus removed, it was possible to assign resonances to most of the amino acids in the terminal extensions. One-dimensional experiments at various pH values provided H-2 chemical shifts for the three terminal extension histidines from which their pKa values were measured. It is concluded that the terminal extensions appear to be of little ordered conformation, are accessible to solvent and flex freely from the main body of the protein. The results of the NMR spectroscopic studies of beta B2-crystallin are in excellent agreement with those for the X-ray crystal structure [Bax, B., Lapatto, R., Nalini, V., Driessen, H., Lindley, P. F., Mahadevan, D., Blundell, T. L. & Slingsby, C. (1990) Nature 347, 776-780]. No change in the spectrum of beta B2 crystallin was observed in the presence of calcium, suggesting that the termini are not involved in calcium binding. PMID- 8477704 TI - 1H-NMR spectroscopy of bovine lens beta-crystallin. The role of the beta B2 crystallin C-terminal extension in aggregation. AB - 1H-NMR spectroscopic studies of bovine eye lens beta-crystallin aggregates (dimer, trimer and octomer) are presented. The NMR spectra for all three beta crystallin aggregates are dominated by resonances from the beta B2 subunit, particularly from the N- and C-terminal extensions of this subunit. Resonances from other beta subunits, which all have terminal extensions, are, in general, absent from spectra of the beta-crystallin aggregates. Therefore, the beta B2 subunit and, in particular its terminal extensions, has enhanced flexibility compared to the other beta-crystallin subunits. Furthermore, resonances arising from the C-terminal extension of beta B2-crystallin are not present in the spectrum of the octomer, which is consistent with the C-terminal extension binding in this aggregate and hence being involved in large aggregate formation. A possible interaction between the C-terminal extension of beta B2 and the hydrophobic beta B1 subunit, which is only found in the octomer, is discussed. At higher temperatures (45 degrees C) in the octomer, partial exposure of the C terminal extension of beta B2 occurs indicating that the octomer may be starting to break up into smaller aggregates. PMID- 8477705 TI - Overproduction, purification and characterization of the bacterioferritin of Escherichia coli and a C-terminally extended variant. AB - The bacterioferritin (BFR) of Escherichia coli is an iron-sequestering haemoprotein composed of 24 identical polypeptide chains forming an approximately spherical protein shell with a central iron-storage cavity. BFR and BFR-lambda, a variant with a 14-residue C-terminal extension, have been amplified (120-fold and 50-fold, respectively), purified by a new procedure and characterized. The overproduced BFR exhibited properties similar to those of natural BFR, but the iron content (25-75 non-haem Fe atoms/molecule) was 13-39-fold lower. Two major assembly states of BFR were detected, a 24-subunit protein (tetracosamer) and a novel haem-containing subunit dimer. BFR-lambda subunits assembled into tetracosamers having the same external-surface properties as BFR, presumably because their C-terminal extensions project into and occupy about 60% of the central cavity. As a result, BFR-lambda failed totake up iron under conditions that allowed incorporation into BFR in vitro. The haem content of BFR-lambda (1-2 haems/tetracosamer) was lower than that of BFR (3.5-10.5 haems/tetracosamer) and this, together with a difference in the visible spectra of the two haemoproteins, suggested that the C-terminal extensions in BFR-lambda perturb the haem-binding pockets. A subunit dimer form of BFR-lambda was not detected. A combination of Mossbauer spectroscopy and electron diffraction showed that the BFR loaded with iron in vitro has a ferrihydrite-like iron core, whereas the in-vivo loaded protein has an amorphous core. PMID- 8477706 TI - Induction of protein phosphorylation, protein synthesis, immediate-early-gene expression and cellular proliferation by intracellular pH modulation. Implications for the role of hydrogen ions in signal transduction. AB - In Syrian hamster embryo cells, intracellular acidification (but not alkalization) results in proliferation, immediate-early-gene expression and tyrosine phosphorylation. In addition, both intracellular acidification and alkalization result in serine/threonine phosphorylation and de novo protein synthesis of specific proteins. Calcium is not mobilized in response to either intracellular alkalization or acidification. Neither intracellular acidification nor alkalization altered the serum proliferative signal while intracellular alkalization (but not acidification) reduced the epidermal-growth-factor-induced proliferative signal, tyrosine phosphorylation and immediate-early-gene expression. Finally, intracellular acidification (but not alkalization) could induce immediate-early-gene expression in cells growing in the presence of serum, indicating that the pH signalling pathway is not down modulated by the serum signalling pathway. These results, while indirect, indicate that hydrogen ions may play an important role in mitogen-signal transduction in Syrian hamster embryo cells. PMID- 8477707 TI - Stimulation of HIT-T15 insulinoma cells by glyceraldehyde does not require its metabolism. AB - The addition of the triose D-glyceraldehyde (5-20 mM) to HIT-T15 hamster insulinoma cells caused a rapid, marked depolarisation of the plasma membrane accompanied by a pronounced intracellular acidification, an increase in the cytosolic free calcium concentration [Ca2+]i and enhanced secretion of insulin. D glyceraldehyde did not reduce the rate of efflux of 86Rb+ from loaded perifused cells. All of the above effects of D-glyceraldehyde were also observed in response to L-glyceraldehyde. The changes in membrane potential and intracellular pH (pHi) caused by D-glyceraldehyde were unaffected by the glycolytic inhibitor iodoacetate, by K(+)-channel blockers (tolbutamide and tetraethylammonium), or by inhibitors of the transport of lactate (alpha-fluorocinnamate), alanine (methylaminoisobutyrate) or glucose (phloretin, phlorrizin). The glyceraldehyde induced depolarisation and acidification were also observed in the absence of extracellular Ca2+ or Na+. The increase in [Ca2+]i evoked by D-glyceraldehyde was reversed by removal of Ca2+ from the medium. The formation of lactate by HIT-T15 cells was not significantly increased by addition of 10 mM D-glyceraldehyde or L glyceraldehyde. In contrast, 10 mM glucose caused an approximately fourfold rise in lactate production. The oxidation of D-glyceraldehyde by HIT-T15 cells was also extremely modest compared to glucose oxidation by these cells. These results suggest that the stimulation of HIT-T15 cells by either D-glyceraldehyde of L glyceraldehyde does not require metabolism of the triose within the cell and may not involve closure of nucleotide-sensitive K+ channels. We propose that the electrogenic transport of glyceraldehyde across the plasma membrane, possibly via H+ cotransport, might lead to depolarisation and hence to Ca2+ entry into the cell. PMID- 8477708 TI - Molecular cloning of a cDNA showing alternative splicing of the 5'-untranslated sequence of mRNA for human aromatase P-450. AB - A new type of full-length cDNA clone encoding human aromatase P-450 was isolated from a human placental cDNA library. The clone, designated as pES-4, has a 3130 bp insert. The nucleotide sequences of the translated region and the 3' untranslated region of the insert of pES-4 are exactly identical with those of the cDNA clone characterized previously. However, the sequence of the 5' untranslated region of the insert has characteristic feature, i.e. an extra sequence of 109 bp is present at a junction between exon 1 and exon 2 on the processed human aromatase mRNA. Analysis of the genomic clones containing the region between exon 1 and exon 2 of the human aromatase P-450 gene reveals that the 109-bp genomic segment, encoding the same sequence as the extra sequence observed in pES-4, is located approximately 10-kbp downstream of exon 1 and that the nucleotide sequences of the 5'-flanking and the 3'-flanking regions of the segment conform to the GT-AG rule for RNA splicing. By means of reverse transcription and polymerase chain reaction, relative amounts of the pES-4-type mRNA are estimated to be approximately 4.8% and 2.3% of the processed aromatase P 450 mRNA in human placenta and human BeWo choriocarcinoma cells, respectively. These results indicate that the segment of 109 bp between exon 1 and exon 2 is a new exon hitherto unidentified and that heterogeneity observed in the 5' untranslated sequence of human aromatase P-450 mRNA is, at least in part, caused by alternative splicing of this new exon. PMID- 8477709 TI - Structures of sialylated oligosaccharides of human erythropoietin expressed in recombinant BHK-21 cells. AB - The native structures of the Asn-linked oligosaccharides and the O-glycans at Ser126 of human erythropoietin expressed from recombinant BHK cells have been elucidated. Enzymatically released N-glycans were studied by methylation analyses, fast-atom-bombardment mass spectrometry as well as one- and two dimensional 1H-NMR spectrometry at 600 MHz. Many (82.7%) were found to be tetraantennary N-acetyllactosamine-type (22.8% with one, 3.6% with two and 0.4% with three N-acetyllactosamine repeats) being tetrasialylated (41%), trisialylated (29.6%) and disialylated (12.2%). A few (9.7%; 4.1% 2,4-branched, 5.6%, 2,6-branched) of the chains were triantennary (5.4% trisialyl, 4.3% disialyl) and 4.6% were of the disialyl diantennary type. Almost all of the innermost GlcNAc residues were alpha 1-6 fucosylated and NeuAc was exclusively alpha 2-3 linked to Gal beta 1-4GlcNAc-R; 60% of the protein was found to be O glycosylated at Ser126; structures were monosialylated (70%) or disialylated (30%) forms of the Gal beta 1-3GalNAc core type. Glycosylation patterns at individual Asn-Xaa-Thr/Ser sites were determined by analytical high-pH anion exchange chromatography with pulsed amperometric detection. Only tetraantennary chains with 0-3 N-acetyllactosamine repeats were detected at Asn38 and Asn83, while almost all of the di- and triantennary oligosaccharides were attached to Asn24. Batch analysis of different preparations of recombinant erythropoietin revealed the high reproducibility of the production procedure. Structures containing terminal GalNAc-GlcNAc were detected in small amounts in a few batches. PMID- 8477710 TI - Two-dimensional NMR assignment of hyperfine-shifted resonances of very fast relaxing metal binding sites of proteins by NOE spectroscopy. The case of Cu, Co superoxide dismutase. AB - The isotropically shifted NMR resonances of bovine Cu, Co superoxide dismutase, arising from the imidazole protons of the metal binding site of the native Cu, Zn enzyme when Zn(II) is replaced by Co(II), were investigated by two-dimensional NMR. NOE spectra have been measured at different mixing times in order to obtain a good set of interproton dipolar connectivities. A number of NOEs were obtained for very fast relaxing resonances close to the paramagnetic copper ion and new isotropically shifted resonances were detected in the proximity of the diamagnetic region. The recently obtained original X-ray coordinates of the Cu, Co enzyme were used in order to give the appropriate values to the interproton distances of the imidazole rings of the copper-coordinated histidines. The data allowed an unequivocal and definitive assignment of the isotropically shifted resonances to be done, with respect to previous results obtained using the coordinates of the Cu, Zn enzyme and monodimensional NMR techniques, which contain a potential source of artifacts in the selective excitation required prior to acquisition of spectra. PMID- 8477711 TI - Expression of the rat growth-hormone gene is under the influence of a cell-type specific silencer element. AB - We have previously shown that a cell-type-specific negative-regulatory element, or silencer, acts to specifically restrict rat-growth-hormone(rGH)-promoter activity to pituitary cells. Here we report a detailed characterization of this element. The activity of the silencer is dependent on its position relative to the promoter. The negative regulatory effect can be diminished by cotransfection with a high-copy-number, silencer-containing competitor plasmid, suggesting that the function of the element is mediated by specific binding of a trans-acting negative-regulatory factor. The minimal region required for silencer function is contained between positions -309 and -266 relative to the start of the rGH mRNA. The specific interaction of a nuclear protein from non-pituitary cells with this rGH DNA segment was shown by DNaseI as well as dimethylsulfate methylation interference footprinting. A detailed examination of the DNA-binding site for that protein clearly suggest that it belongs to the NF1 family of transcription factors. PMID- 8477712 TI - Overproduction, solubilization, purification and DNA-binding properties of AmpR from Citrobacter freundii. AB - AmpR belongs to the LysR family of prokaryotic DNA-binding transcriptional regulators and controls induction of the enterobacterial ampC beta-lactamase gene. The ampR gene of Citrobacter freundii was deregulated by employing the polymerase chain reaction to introduce an efficient ribosome-binding sequence and suitable restriction enzyme sites for cloning into a chemically inducible tac promoter expression vector. When induced in Escherichia coli, the modified ampR gene rapidly overproduced the AmpR protein as an insoluble aggregate. The AmpR protein could be solubilized with 1.32 M guanidine/HCl and remained soluble when dialyzed against 0.5 M NaCl. The solubility properties of AmpR were exploited to selectively precipitate and resolubilize the protein in a nearly homogenous state. AmpR was then purified by a single gel-filtration chromatography step which demonstrated that AmpR exists in solution as a monodisperse homodimeric protein. Several milligrams of purified AmpR could be obtained routinely from a 1 1 culture of induced bacteria. A DNA-binding assay buffer containing 300 mM potassium glutamate and 30% glycerol was found to stabilize AmpR and used to demonstrate sequence-specific DNA-binding. Additionally, purified AmpR binds a half-operator DNA with an inverted-repeat sequence which competes with binding by the wild-type operator. These findings are discussed in terms of the helix-turn helix DNA-binding motif, whereby AmpR is proposed to interact with its wild-type operator as a dimer of dimers. PMID- 8477713 TI - The interactions of retinoids with retinol-binding protein. A resonance Raman spectroscopic study. AB - We have measured the pre-resonance Raman spectrum of retinal, retinoic acid and retinol in dilute CCl4 solutions and when bound to the bovine-serum retinol binding protein. The comparison reveals that the binding interaction does not involve any specific interactions of the head group and/or the polyene chain with a particular protein residue. The data indicate hydrogen bonding of bound retinal's head-group oxygen to water, as well as some torsional angle change of its polyene chain upon binding. PMID- 8477714 TI - Purification and characterization of extracellular, acidic chitinase isoenzymes from elicitor-stimulated parsley cells. AB - Treatment of cultured parsley cells (Petroselinum crispum) with fungal elicitor caused large increases in the activities of chitinase and 1,3-beta-glucanase. Chitinase activity accumulated predominantly in the culture medium, whereas 1,3 beta-glucanase activity was located almost exclusively intracellularly. Extracellular chitinase activity was resolved into six different isoenzymes, all of which were purified and characterized. All six isoforms were acidic proteins (pI 3.8-5.3), with molecular mass 30-38 kDa. Four were exochitinases and two were endochitinases. The most abundant isoform also showed lysozyme activity. Three of the exochitinases were glycoproteins and two of these were reactive with an antiserum specific for xylose in complex glycosidic structures. The exochitinases constituted relatively small proportions of the total chitinase activity and may serve a different function in cellular metabolism compared to the more abundant endochitinases. PMID- 8477715 TI - Influence of conjugation of doxorubicin to transferrin on the iron uptake by K562 cells via receptor-mediated endocytosis. AB - The influence of conjugation of doxorubicin to holotransferrin on the receptor mediated endocytosis of and on the iron uptake from transferrin was studied using K562 cells. 125I-labelled transferrin and doxorubicin-transferrin conjugates were used in the binding, dissociation, and ligand-exchange experiments at 0 degree C, and 59Fe,125I-labelled (double-labelled) ligands were used in the endocytosis, iron uptake, and recycling experiments at 37 degrees C. The binding affinity of conjugates was about half of that of transferrin. Binding of 125I-labelled ligands was blocked by both unlabelled ligands to the same degree, however, it was not blocked at all by an 8000-fold excess of doxorubicin. After saturation bindings, slightly more 125I-labelled conjugates dissociated from the surface of cells than transferrin. Exchange of 125I-labelled ligands for unlabelled ligands resulted in different EC50 values (defined as the concentration of unlabelled ligand at which half as much radioligand is exchanged for unlabelled ligand as would be exchanged at infinitely high concentration of unlabelled ligand under similar assay conditions). While transferrin exchanged transferrin with an EC50 value close to the binding affinity, conjugates exchanged conjugates with much lower efficiency. The heterolog exchange experiments yielded EC50 values inbetween the two extrema. For studying iron uptake, K562 cells were loaded with the double-labelled ligands either at 37 degrees C (endosome-loading only) or at 0 degree C (surface-loading only). Results obtained for the endocytosis of, the iron uptake from, and the recycling of double-labelled ligands indicate that (a) the rate of iron uptake is smaller from conjugates than from transferrin, (b) there are at least two parallel recycling processes for both ligand.receptor complexes, and (c) each time constant characterizing the different steps of iron uptake via receptor-mediated endocytosis is smaller for conjugates than for transferrin (or, the half times characterizing the different steps are higher for conjugates than for transferrin). Endocytosis and iron uptake were unaffected by free doxorubicin (12.5 microM) or colchicine (1 mM). Benzyl alcohol (30 mM) slowed down the rate of both endocytosis and iron uptake, while dithiothreitol (5 mM) decreased the rate of iron uptake and increased the rate of endocytosis. N Ethylmaleimide (1 mM) completely stopped both endocytosis and iron uptake. The results suggest that the binding of conjugates to the surface of cells is governed by the binding of the transferrin part of conjugates to the transferrin receptor. However, conjugation of doxorubicin to transferrin seems to influence all properties of transferrin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477716 TI - Structural determination of the capsular polysaccharide produced by Klebsiella pneumoniae serotype K40. NMR studies of the oligosaccharide obtained upon depolymerisation of the polysaccharide with a bacteriophage-associated endoglycanase. AB - The Klebsiella pneumoniae K40 capsular polysaccharide has been isolated and investigated by use of methylation analysis, specific degradations and NMR spectroscopy. The polysaccharide was depolymerised by a bacteriophage-associated endogalactosidase, and the resulting oligosaccharide was characterised by one dimensional and two-dimensional NMR spectroscopy and direct chemical ionisation MS. The repeating unit of the K40 capsular polysaccharide was shown to be a linear hexasaccharide with the composition-->3)- alpha-L-Rhap-(1-->2)-alpha-L Rhap-(1-->4)-alpha-D-GlcpA++ +-(1-->2-)- alpha-D-Manp-(1-->2)-alpha-D-Manp-(1- >3)-alpha-D-Galp-(1--> (Rha, rhamnose). PMID- 8477717 TI - Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM. AB - We have demonstrated that a 72-kDa non-receptor-type protein-tyrosine kinase (p72syk) was co-immunoprecipitated with membrane IgM in digitonin lysates of porcine tonsillar cells and was rapidly activated following the engagement of membrane IgM. This activation was occurred within 5 s, even in the presence of EGTA and 5,5'-dimethyl-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid as extracellular and intracellular Ca(2+)-chelating agents, respectively, as well as in the presence of the protein-kinase-C inhibitor, H-7. Additionally, genistein, a potent protein-tyrosine kinase inhibitor, was capable of reducing both IgM stimulated Ca2+ mobilization and p72syk activation in a dose-dependent manner. These results indicate that p72syk is physically associated with the B-cell antigen receptor, participating in antigen-mediated signal transduction in both a Ca(2+)-independent and protein-kinase-C-independent manners. PMID- 8477718 TI - Cell-specific expression of human beta-galactoside alpha 2,6-sialyltransferase transcripts differing in the 5' untranslated region. AB - In humans, two cDNAs have been isolated encoding beta-galactoside alpha 2,6 sialyltransferase, differing only in part of the 5' untranslated region. Primer extension data show that the two cDNAs are near full-length clones. RNase protection analysis of different cell types showed that the transcript corresponding to the alpha 2,6-sialyltransferase cDNA isolated from a B-cell library resided only in mature B cells. In contrast, the transcript corresponding to the alpha 2,6-sialyltransferase cDNA isolated from a placenta library was found in all cells tested. Our results also indicate the existence of a third alpha 2,6-sialyltransferase transcript in the hepatoma cell line HepG2. Mature B cells were found to express high amounts of alpha 2,6-sialyltransferase mRNA, compared to other cell types tested, as shown by Northern blot analysis. Moreover there was an increased expression of beta-galactoside alpha 2,6-sialyltransferase mRNA in activated B cells compared to resting B cells. In vitro transcription and translation of the cDNAs resulted in a protein of 45 kDa, but the transcripts were translated with different efficiency, suggesting a role for the 5' untranslated region in regulation of translation. We have also made an alpha 2,6 sialyltransferase construct lacking the specific 5' regions of the two cDNAs. A transcript generated from this construct was translated more efficiently in vitro than the two alpha 2,6-sialyltransferase cDNAs. PMID- 8477719 TI - Exchange reactions catalyzed by group-transferring enzymes oppose the quantitation and the unravelling of the identify of the pentose pathway. AB - 1. The distributions and rates of transfer of carbon isotopes from a selection of specifically labelled ketosugar-phosphate substrates by exchange reactions catalyzed by the pentose and photosynthetic carbon-reduction-pathway group transferring enzymes transketolase, transaldolase and aldolase have been measured using 13C-NMR spectroscopy. 2. The rates of these exchange reactions were 5, 4 and 1.5 mumol min-1 mg-1 for transketolase exchange, transaldolase exchange and aldolase exchange, respectively. 3. A comparison of the exchange capacities contributed by the activities of these enzymes in three in vitro liver preparations with the maximum non-oxidative pentose pathway flux rates of the preparations shows that transketolase and aldolase exchanges exceeded flux by 9 19 times in liver cytosol and acetone powder enzyme preparations and by 5 times in hepatocytes. Transaldolase was less effective in the comparison of exchange versus flux rates: transaldolase exchange exceeded flux by 1.6 and 5 in catalysis by liver cytosol and acetone powder preparations, respectively, but was only 0.6 times the flux in hepatocytes. 4. Values of group enzyme exchange and pathway flux rates in the above three preparations are important because of the feature role of liver and of these particular preparations in the establishment, elucidation and measurement of a proposed reaction scheme for the fat-cell-type pentose pathway in biochemistry. 5. It is the claim of this paper that the excess of exchange rate activity (particularly transketolase exchange) over pathway flux will overturn attempts to unravel, using isotopically labelled sugar substrates, the identity, reaction sequence and quantitative contribution of the pentose pathway to glucose metabolism. 6. The transketolase exchange reactions relative to the pentose pathway flux rates in normal, regenerating and foetal liver, Morris hepatomas, mammary carcinoma, melanoma, colonic epithelium, spinach chloroplasts and epididymal fat tissue show that transketolase exchange may exceed flux in these tissues by factors ranging over 5-600 times. 7. The confusion of pentose pathway theory by the effects of transketolase exchange action is illustrated by the 13C-NMR spectrum of the hexose 6-phosphate products of ribose 5-phosphate dissimilation, formed after 30 min of liver enzyme action, and shows 13C-labelling in carbons 1 and 3 of glucose 6-phosphate with ratios which range over 2.1-6.4 rather than the mandatory value of 2 which is imposed by the theoretical mechanism of the pathway. PMID- 8477720 TI - Comparative proteolysis of sorbitol and alcohol dehydrogenases. AB - Mammalian alcohol and sorbitol dehydrogenases, with distantly related subunits but different substrates, quaternary structures and zinc contents, were evaluated by comparison of their sensitivities to proteases. Sorbitol dehydrogenase is more sensitive to proteolysis than alcohol dehydrogenase, but both enzymes show limited cleavage with Lys-specific and Glu-specific proteases. With the former, the major cleavage in both proteins involves Lys-Lys-Pro segments, at positions 247-248 in alcohol dehydrogenase, surface-positioned after the most distal beta strand in the coenzyme-binding domain, and at 61-62 in sorbitol dehydrogenase, at another surface in the catalytic domain. Further cleavages affect these two and a third surface. A non-surface cleavage was obtained with the Glu-specific protease and sorbitol dehydrogenase, after insufficient protease inhibition before analysis by SDS/PAGE. It probably reflects non-native conditions, and the fact that this protease is active in strong SDS, necessitating pre-analytical use of a specific inhibitor. Differences in cleavage patterns between the two proteins do not involve areas corresponding to the dimer interactions in alcohol dehydrogenase. Hence, these areas are likely to be the same in sorbitol dehydrogenase. However, major differences involve regions that flank the surface which has a 20-residue loop segment in alcohol dehydrogenase that is missing in sorbitol dehydrogenase. This segment, previously highlighted from comparisons, is therefore also emphasized by experimental results with proteolysis. The surface exposed by the missing segment is likely to correlate with the separate quaternary structures and to indicate possible sites for the additional subunit interactions in the sorbitol dehydrogenase tetramer versus the alcohol dehydrogenase dimer. PMID- 8477721 TI - Amino acid residues involved in the catalytic site of human erythrocyte bisphosphoglycerate mutase. Functional consequences of substitutions of His10, His187 and Arg89. AB - Human bisphosphoglycerate mutase (GriP2 mutase) is a trifunctional enzyme which synthesizes and degrades GriP2 in red cells. Among the amino acid residues involved in its active site there are two conserved histidine residues, His10 which is phosphorylated during the catalytic process and His187 for which only speculative data have been made about the potential role during the reactions. Another amino acid residue, Arg89, had not been described as part of this active site but we have recently shown that a natural mutant Arg89-->Cys was highly thermolabile and showed severe perturbations of its enzymatic properties. To understand better the exact role of these residues, replacements of His10 by Gly (H10G) or Asp (H10D), His187 by Asn (H187N), Tyr (H187Y) or Asp (H187D) and Arg89 by Cys (R89C), Ser (R89S), Gly (R89G) or Lys (R89K) were performed by site directed mutagenesis. The results obtained in this report show that replacement of the His10 residue completely abolished the enzymatic activities. Concerning the His187 residue, our results afford arguments that it plays an essential role in the three catalytic activities. Indeed all these activities are abolished in the two H187Y and H187D variants, whereas they are detectable though strongly diminished, for the H187N variant. In addition mutations at His187 could be distinguishable from those at His10 since the former resulted in a thermolabile enzyme, whereas no significant change in heat stability was observed for the latter. It is noteworthy that the H187N variant is protected against thermal instability by glycerate 2,3-bisphosphate (GriP2). Concerning the Arg89 mutants, R89C, R89S and R89G, the three variants showed characteristics identical to those found in the natural R89C mutant, i.e. loss of 99% of synthase activity, consistent decrease of mutase and 2-phosphoglycolate-stimulated phosphatase activities whereas the unstimulated phosphatase activity was normal. Moreover these mutants were unstable at 55 degrees C but GriP2 was able to protect them against thermal instability. In contrast, the R89K mutant was stable at 55 degrees C. Its synthase and unstimulated phosphatase activities were normal but its mutase and 2-phosphoglycolate-stimulated phosphatase activities were decreased. In addition, Km values for monophosphoglycerates were increased (3.2 fold) in the synthase but normal in mutase activities, whereas Km values for GriP2 were normal in mutase and phosphatase activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8477722 TI - Heavy-chain isoforms of non-muscle myosin in human tissues. AB - The heavy-chain isoforms of myosin in human non-muscle and smooth muscle tissues were analyzed by means of SDS/PAGE and using three distinct newly developed monoclonal anti-(human cerebrum myosin) Ig (HBM-1, HBM-3 and HBM-4). Purified cerebrum myosin contained three electrophoretic variants of non-muscle myosin heavy chain (NM1, NM2 and NM3, with apparent molecular masses of about 200, 198 and 196 kDa, respectively). Both NM1 and NM2 were recognizable by the brain specific antibody HBM-1, while NM3 was recognizable by HBM-3. Each of the variants reacted with HBM-4 to a similar extent. Purified cerebellum myosin gave three electrophoretic variants of the heavy chain which were indistinguishable electrophoretically or immunologically from those of cerebrum myosin. Aortic myosin contained four electrophoretic variants, including the two smooth muscle myosin heavy chain isoforms and NM2-like and NM3-like heavy chains. Liver, platelet and kidney myosins contained a heavy chain very similar to NM3. Kidney myosin also contained a small fraction of an NM2-like electrophoretic variant. In addition, cerebrum, kidney, liver and platelet myosins appeared to contain minor, 194-kDa myosin heavy-chain-like polypeptide(s) (NM4). NM1, as well as NM2 and NM3, thus appear to be the brain-type and non-brain-type non-muscle myosin heavy chain isoforms, respectively, and additional minor heavy-chain isoforms are also likely to be present in human tissues. PMID- 8477723 TI - Crystallographic studies of azide binding to human carbonic anhydrase II. AB - The crystal structures of human carbonic anhydrase II (CAII) at pH 5.7 and 8.0 have been determined at 0.21-nm resolution in the presence of 20 mM azide, which is a noncompetitive inhibitor of the CAII-catalyzed CO2 hydration reaction. Although azide often facilitates the crystallization of CAII and its variants, this small anion does not cause any significant structural changes in the enzyme active site or in the overall protein structure, and zinc coordination remains tetrahedral over the pH range 5.7-8.0. Importantly, the binding of azide at pH 8.0 has implications for the zinc-binding mode of the catalytic product, bicarbonate ion. Since azide is a competitive inhibitor of the reverse reaction of bicarbonate dehydration, and since the zinc-bound azide nitrogen makes a non hydrogen-bonded van der Waals contact with the hydroxyl group of Thr199, it is possible that a zinc-bound bicarbonate oxyanion could likewise make a non hydrogen-bonded, van der Waals contact with the hydroxyl group of Thr199. Therefore, the donation of a hydrogen bond to Thr199 is not absolutely required for anion binding to tetracoordinate zinc. PMID- 8477724 TI - Arginine 53 is involved in head-group specificity of the active site of porcine pancreatic phospholipase A2. AB - The X-ray structure of a mutant porcine pancreatic phospholipase A2 inhibitor complex [Thunnissen et al. (1990) Nature 347, 689-691] has been determined. This structure shows several interactions between the sn-2-acyl chain and the phosphate moiety of the inhibitor at sn-3 and the protein. The interactions of the remaining part of the polar head group are less clear. Because Arg53 is in close proximity to the head group, we tested the importance of charge at position 53 on enzymatic activity and specificity. Arg53 has been replaced by a glutamine and a glutamic acid in mutants R53Q and R53E, respectively. The effects of the mutations were tested with both zwitterionic and anionic substrates. With monomeric, zwitterionic, (R,S)-1,2-dihexanoyldithiopropyl-3-phosphocholine as substrate, the mutants R53Q and R53E display twofold and sevenfold, respectively, increased kcat/Km values, composed of increased kcat and decreased Km values. Tested on micelles of zwitterionic (R)-1,2-dioctanoylglycero-3-phosphocholine the mutants R53Q and R53E are more active than the native enzyme, whereas these mutations have an opposite effect on the activity on anionic (R)-1,2 dioctanoylglycero-3-phosphoglycol. Thus, whereas the native enzyme is 0.3 times as active on zwitterionic as on the anionic substrate, these ratios are 1.0 (R53Q) and 1.7 (R53E) for the mutants. No changes in activity were observed with the anionic substrate (R)-1,2-dioctanoylglycero-3-sulfate. Binding studies with substrate-derived inhibitors confirmed the increased affinity for zwitterionic phospholipids and the reduced affinity for anionic phospholipids. The kinetic and binding data indicate the involvement of the charge of residue 53 in head-group specificity and suggest a position of residue 53 closer to the choline or glycol than to the phosphate. PMID- 8477725 TI - Purification of a cytochrome b containing H2:heterodisulfide oxidoreductase complex from membranes of Methanosarcina barkeri. AB - The reduction of CoM-S-S-HTP, the heterodisulfide of coenzyme M (H-S-CoM) and N-7 mercaptoheptanoylthreonine phosphate (H-S-HTP), with H2 is an energy-conserving step in methanogenic archaea. We report here that in Methanosarcina barkeri this reaction is catalyzed by a membrane-bound multienzyme complex, designated H2:heterodisulfide oxidoreductase complex, which was purified to apparent homogeneity. The preparation was found to be composed of nine polypeptides of apparent molecular masses 46 kDa, 39 kDa, 28 kDa, 25 kDa, 23 kDa, 21 kDa, 20 kDa, 16 kDa, and 15 kDa and to contain 3.2 nmol cytochrome b, 70 to 80 nmol non-heme iron and acid-labile sulfur, 5 nmol Ni, and 0.6 nmol FAD per mg protein. The 23 kDa polypeptide possessed heme-derived peroxidase activity indicating that this polypeptide is the cytochrome b. The purified H2:heterodisulfide oxidoreductase complex catalyzed the reduction of CoM-S-S-HTP with H2 at a specific activity of 6 U/mg protein (1 U = 1 mumol.min-1), the reduction of benzylviologen with H2 at a specific activity of 66 U/mg protein and the reduction of CoM-S-S-HTP benzylviologen with H2 at a specific activity of 66 U/mg protein and the reduction of CoM-S-S-HTP HTP with reduced benzylviologen at a specific activity of 24 U/mg protein. The complex did not mediate the reduction of coenzyme F420 with H2 nor the oxidation of reduced coenzyme F420 with CoM-S-S-HTP. The reduced cytochrome b in the enzyme complex could be oxidized by CoM-S-S-HTP and re reduced by H2. The specific rates of cytochrome oxidation and reduction were too high to be resolved under our experimental conditions. The findings suggest that the H2:heterodisulfide oxidoreductase complex is composed of a F420-non-reducing hydrogenase, a cytochrome b and heterodisulfide reductase and that cytochrome b is a redox carrier in the electron transport chain involved in CoM-S-S-HTP reduction with H2. PMID- 8477726 TI - Purification and properties of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanobacterium thermoautotrophicum. AB - N5-Methyltetrahydromethanopterin:coenzyme M meth-yltransferase is an integral membrane protein found in methanogenic archaea. It catalyzes an energy-conserving step in methane formation from CO2 and from acetate. The enzyme from Methanobacterium thermoautotrophicum (strain Marburg) has been purified 30-fold to apparent homogeneity. The purified enzyme had an apparent molecular mass of 670 kDa and was composed of seven different polypeptides of 34 kDa, 28 kDa, 24 kDa, 23 kDa, 21 kDa, 13 kDa, and 12 kDa. The N-terminal amino acid sequences of these polypeptides were determined. The native 670-kDa enzyme was found to contain 7.6 mol 5-hydroxybenzimidazolyl cobamide/mol, 37 mol non-heme iron/mol and 34 mol acid-labile sulfur/mol. Cobalt analyses after sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that the corrinoid was bound to the 23-kDa polypeptide. The apparent molecular masses of the polypeptides given above were determined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis without boiling the samples prior to analysis. When the samples were boiled, as is usually done, the 23-kDa polypeptide changed its apparent molecular mass to 33 kDa and the 21-kDa, 24-kDa, and 28-kDa polypeptides formed aggregates. The specific activity (apparent Vmax) of the purified methyltransferase preparation was 11.6 mumol.min-1.mg protein-1. The apparent Km for N5-methyltetrahydromethanopterin was 260 microM and that for coenzyme M was 60 microM. The preparation was absolutely dependent on the presence of Ti(III) for activity. ATP enhanced the activity 1.5-2-fold. PMID- 8477727 TI - Transcriptional control of AAC3 gene encoding mitochondrial ADP/ATP translocator in Saccharomyces cerevisiae by oxygen, heme and ROX1 factor. AB - The AAC3 gene of Saccharomyces cerevisiae encodes a mitochondrial ADP/ATP translocator which is subject to oxygen repression. Evidence is presented here, that the repression of AAC3 expression is dependent upon heme and the ROX1 factor. The promoter region of the AAC3 gene was isolated, sequenced, and deletion analysis was performed using lacZ as a reporter gene to determine the cis-acting regions responsible for the regulation of AAC3 expression. The results of the deletion analysis show that the negative control of the AAC3 gene by oxygen and ROX1 factor is mediated by an upstream repression sequence consisting of a T-rich segment adjacent to the consensus elements that are present in the 5' flanking regions of several other yeast genes. An additional upstream repressor site was located within the AAC3 promoter which, however, is not related either to oxygen or to ROX1 factor. The data presented here delineate the main cellular factors and DNA sequences involved in the regulatory mechanism by which an essential function for anaerobic cells growth, ADP/ATP translocation, is ensured. In addition, they show that the AAC3 gene belongs to the family of yeast genes including TIF51B, COX5b, HEM13 and CYC7 that are negatively regulated by oxygen and heme. PMID- 8477728 TI - Enzymes of anaerobic metabolism of phenolic compounds. 4-Hydroxybenzoate-CoA ligase from a denitrifying Pseudomonas species. AB - The initial step of anaerobic 4-hydroxybenzoate and 3-hydroxybenzoate degradation was studied in a denitrifying Pseudomonas sp. 4'-Hydroxybenzoate and 3 hydroxybenzoate are converted into their coenzyme A (CoA) thioesters by two different specific coenzyme A ligases. 4-Hydroxybenzoate-CoA ligase (AMP-forming) was purified 350-fold. The ligase is active as a monomer of molecular mass 48 kDa, as determined by gel filtration and SDS/PAGE. At a pH optimum of 8.5, the apparent Km values for 4-hydroxybenzoate, ATP, and coenzyme A are 37 microM, 77 microM, and 125 microM, respectively. The enzyme reacts specifically with 4 hydroxybenzoate (100%) and 4-aminobenzoate (30%). Other analogues of benzoate, notably 3- or 2-hydroxybenzoate, are inactive, and 2,4-dihydroxybenzoate and 2 hydroxy-4-methylbenzoate act as competitive inhibitors (Ki = 1 microM). Polyclonal antibodies were raised and used in immunoblot assays to study the regulation of the expression of 4-hydroxybenzoate-CoA ligase. The ligase is synthesized when cells are grown anaerobically with 4-hydroxybenzoate, phenol, or p-cresol; phenol and p-cresol are degraded via 4-hydroxybenzoate. The enzyme is not present in cells grown aerobically with 4-hydroxybenzoate or anaerobically with benzoate or 4-hydroxyphenylacetate. PMID- 8477729 TI - Enzymes of anaerobic metabolism of phenolic compounds. 4-Hydroxybenzoyl-CoA reductase (dehydroxylating) from a denitrifying Pseudomonas species. AB - The reductive removal of aromatic hydroxyl functions plays an important role in the anaerobic metabolism of many phenolic compounds. We describe a new enzyme from a denitrifying Pseudomonas sp., 4-hydroxybenzoyl-CoA reductase (dehydroxylating), which reductively dehydroxylates 4-hydroxybenzoyl-CoA to benzoyl-CoA. The enzyme plays a role in the anaerobic degradation of phenol, 4 hydroxybenzoate, p-cresol, 4-hydroxyphenylacetate, and other aromatic compounds of which 4-hydroxybenzoyl-CoA is an intermediate. The enzyme is therefore induced only under anoxic conditions with these aromatic substrates, but not with benzoate or under aerobic conditions. A similar enzyme which reductively dehydroxylates 3-hydroxybenzoyl-CoA is induced during anaerobic growth with 3 hydroxybenzoate. The soluble enzyme 4-hydroxybenzoyl-CoA reductase was purified. It has a molecular mass of 260 kDa and consists of three subunits of 75, 35, and 17 kDa. The subunit composition is likely to be a2b2c2. The enzyme contains 12 mol iron/mol and 12 mol acid-labile sulfur/mol and exhibits a typical ultraviolet/visible spectrum of an iron-sulfur protein. The reaction requires a reduced electron donor such as reduced viologen dyes; no other co-catalysts are required, the product is benzoyl-CoA and oxidized dye. The reductase is rapidly inactivated by oxygen. The inactivation by low concentrations of cyanide or azide in a pseudo-first-order time course suggests that it may contain a transition metal in an oxidation state which reacts with these ligands. 4-Hydroxybenzoyl-CoA reductase represents a type of enzyme which is common in anaerobic aromatic metabolism of phenolic compounds. A similar enzyme is demonstrated in Rhodopseudomonas palustris anaerobically grown with 4-hydroxybenzoate. The biological significance of reductive dehydroxylation of aromatics and a possible reaction mechanism similar to the Birch reduction are discussed. PMID- 8477730 TI - Troponin-C mutants with increased calcium affinity. AB - Binding of two Ca2+ to the regulatory sites I and II of troponin C (TnC) induces a conformational transition believed to be responsible for the activation of muscle contraction. Based on the known crystal structure (2Ca2+ state), a model for the transition to the 4Ca2+ state has been proposed [Herzberg, O., Moult, J. & James, M. N. G. (1986) J. Biol. Chem. 261, 2638-2644]. The proposed conformational transition predicts that during Ca2+ binding a number of nonpolar residues become exposed to the solvent, creating a hydrophobic patch. Such a model implies that mutation of the hydrophobic to polar residues should increase the Ca2+ affinity at the regulatory sites and reduce the Ca2+ concentration necessary for muscle activation. To test this prediction, we have constructed and functionally characterized two troponin-C mutants (V45T and M48A mutations). Direct calcium-binding measurements in the mutants demonstrate an increase in the Ca2+ affinity for two low-affinity sites. Replacement of endogenous troponin C in skinned muscle fibers by TnC with mutations V45T or M48A increased the Ca2+ sensitivity of their tension development. These results show that the model can be used to construct mutants that regulate muscle contraction at lower Ca2+ concentrations. They provide further experimental support for the proposed calcium-induced conformational change of troponin C and suggest that the predicted transition plays a central role in the activation of the thin filament. PMID- 8477731 TI - Amino acid sequence of Coprinus macrorhizus peroxidase and cDNA sequence encoding Coprinus cinereus peroxidase. A new family of fungal peroxidases. AB - Sequence analysis and cDNA cloning of Coprinus peroxidase (CIP) were undertaken to expand the understanding of the relationships of structure, function and molecular genetics of the secretory heme peroxidases from fungi and plants. Amino acid sequencing of Coprinus macrorhizus peroxidase, and cDNA sequencing of Coprinus cinereus peroxidase showed that the mature proteins are identical in amino acid sequence, 343 residues in size and preceded by a 20-residue signal peptide. Their likely identity to peroxidase from Arthromyces ramosus is discussed. CIP has an 8-residue, glycine-rich N-terminal extension blocked with a pyroglutamate residue which is absent in other fungal peroxidases. The presence of pyroglutamate, formed by cyclization of glutamine, and the finding of a minor fraction of a variant form lacking the N-terminal residue, indicate that signal peptidase cleavage is followed by further enzymic processing. CIP is 40-45% identical in amino-acid sequence to 11 lignin peroxidases from four fungal species, and 42-43% identical to the two known Mn-peroxidases. Like these white rot fungal peroxidases, CIP has an additional segment of approximately 40 residues at the C-terminus which is absent in plant peroxidases. Although CIP is much more similar to horseradish peroxidase (HRP C) in substrate specificity, specific activity and pH optimum than to white-rot fungal peroxidases, the sequences of CIP and HRP C showed only 18% identity. Hence, CIP qualifies as the first member of a new family of fungal peroxidases. The nine invariant residues present in all plant, fungal and bacterial heme peroxidases are also found in CIP. The present data support the hypothesis that only one chromosomal CIP gene exists. In contrast, a large number of secretory plant and fungal peroxidases are expressed from several peroxidase gene clusters. Analyses of three batches of CIP protein and of 49 CIP clones revealed the existence of only two highly similar alleles indicating less peroxidase polymorphism in C. cinereus strains than observed in plants and white-rot fungi. PMID- 8477732 TI - Responses of metabolic systems to large changes in enzyme activities and effectors. 1. The linear treatment of unbranched chains. AB - This first paper in a series investigates the problem of predicting and analysing the effects of large changes in enzyme activities or external nutrients/effectors on metabolic fluxes. We introduce the concept of a deviation index, D, which gives a measure of the relative change in a metabolic variable (e.g. flux) due to a large (non-infinitesimal) relative change in a parameter (e.g. enzyme). Using simplifying kinetic assumptions we have found, for an unbranched metabolic chain, a direct relationship between deviation indices and flux control coefficients. This relationship provides a method to estimate flux control coefficients using a single large change in enzyme activity. We also provide a method of predicting the effects of, for example, DNA manipulation or other techniques for enzyme activity/concentration changes on metabolic fluxes. Up-modulations of single enzymes rarely produce significant changes in fluxes. We show that combined changes of activity of a group of enzymes will produce a more than 'additive' response. We provide a method of predicting the effects of these combined changes, given either the flux control coefficients of the group of enzymes or the effects on the flux of changing the enzymes individually. A similar analysis is carried out for large changes in external nutrients or effectors. These amplification factors, f, give experimentally accessible estimates of the expected changes in metabolic variables. We provide three 'case studies' to illustrate our results. PMID- 8477733 TI - Responses of metabolic systems to large changes in enzyme activities and effectors. 2. The linear treatment of branched pathways and metabolite concentrations. Assessment of the general non-linear case. AB - We extend the analysis of unbranched chains (preceding paper) to large parameter changes in branched systems using linear kinetic assumptions. More complex relationships between flux control coefficients and deviation indices are established. In particular, the deviation index in such systems depends on more than one control coefficient as well as on the magnitude of the enzyme change. Non-additivity of the indices is the general rule. Combined changes of groups of enzymes, whether co-ordinate or not, have also been formulated. Control coefficients can be estimated from a small number of independent large-change experiments. Alternatively, the amplification factors can be calculated given the knowledge of the control coefficients. A 'case study' using published data is presented. The movement of intermediate metabolites as a consequence of large parameter changes can be dealt with in a similar manner. Experimental methods for showing the admissibility of assuming the simplifying assumptions used are summarised. Some simulation studies show possible limits of the application of the approach and some aspects of the general, non-linear, case are discussed. It is concluded that, although metabolic systems are in principle non-linear, many behave, in practice, as quasi-linear systems. The relationships established between deviation indices and control coefficients therefore provide a practical way of predicting the effects of large-scale changes in parameters for many metabolic systems. PMID- 8477734 TI - Substrate interactions between trypanothione reductase and N1 glutathionylspermidine disulphide at 0.28-nm resolution. AB - The enzyme trypanothione reductase has been identified as a prime target for the rational design of inhibitors which may have clinical use in the treatment of tropical diseases caused by the genera Trypanosoma and Leishmania. To aid the design or identification of new inhibitors of this enzyme we have elucidated the structural detail of a trypanothione reductase complexed with one of the naturally occurring substrates, N1-glutathionylspermidine disulphide, by single crystal X-ray diffraction methods at 0.28-nm resolution. The model for the Crithidia fasciculata enzyme-substrate complex has an R-factor of 14.8% and root mean-square deviations of 0.0015 nm and 3.3 degrees on bond lengths and angles respectively. Hydrogen bonding and van der Waals interactions between the enzyme and substrate are dominated by the amino acid side chains. The substrate binds in a rigid active site such that one glutathione moiety is in a V-shape, the other in an extended conformation. One spermidine moiety binds closely to a hydrophobic patch in the active site formed by a tryptophan and a methionine. Distances between the methionine S delta and the terminal N of this spermidine suggest that a hydrogen bond may supplement the hydrophobic interactions in this part of the active site. PMID- 8477735 TI - The structure of the gene encoding chicken ribosomal protein L37a. AB - The nucleotide sequence of the gene encoding chicken ribosomal protein L37a was determined. The gene was 2626 bp long and distributed in four exons and three introns. The transcription initiation site is located at a cytidine residue in a tract of 16 pyrimidines flanked by (G + C)-rich regions. Neither canonical TATA nor the CAAT box was found in the 5'-flanking region. The region from nucleotides -78 to -35 was shown to be important for promoter activity and also to be a binding site for nuclear proteins. This region contains two copies of the sequence [sequence: see text] that is common to many ribosomal protein genes of higher eukaryotes. PMID- 8477736 TI - Channelling can affect concentrations of metabolic intermediates at constant net flux: artefact or reality? AB - We show that if a metabolic intermediate is directly transferred ('channelled') from an enzyme that catalyses its production to another that uses it as substrate, there is no change in its free concentration compared with a system with the same net flux in which there is no direct transfer. Thus the widespread idea that channelling provides a mechanism for decreasing metabolite concentrations at constant flux is false. Results from computer simulation that suggest otherwise [Mendes, P., Kell, D. B. & Westerhoff, H. V. (1992) Eur. J. Biochem. 204, 257-266] are artefacts either of variations in flux or of alterations in opposite directions of the activities of the relevant enzymes. PMID- 8477737 TI - Functional expression and characterization of a Xenopus laevis peptidylglycine alpha-amidating monooxygenase, AE-II, in insect-cell culture. AB - The alpha-amidating reaction of peptide hormones is a two-step process which is catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase (PHL). There are three types of mRNA for these amidating enzymes in Xenopus laevis, namely AE-I, AE-II and AE-III. AE-I encodes only PHM and AE-III encodes both PHM and PHL. AE-II seems to encode subtypes of both PHM and PHL. While AE-II mRNA is present in high amounts in frog skin, the actual enzymes originating from AE-II have not been detected. When we expressed AE-II in cultured insect-cells using the baculovirus expression vector system, the expressed enzyme was specifically localized to the membrane fraction due to its hydrophobic transmembrane domain. Alternatively, when the transmembrane domain-deleted AE-II (Met1-Ile731) was expressed, the enzyme was secreted into the culture medium; this secreted enzyme was purified to homogeneity by a simple two-step procedure. We have verified that the reaction product of the purified enzyme was the amidated peptide, indicating that AE-II has the ability to catalyze the entire amidating reaction. PMID- 8477738 TI - Intron-exon structure, alternative use of promoter and expression of the mouse collagen X gene, Col10a-1. AB - The entire mouse collagen X gene (Col10a-1) has been isolated. The gene is composed of three exons and two introns spanning 7.0 kb of the DNA sequence. Exons 2 and 3 together encode 15-bp of 5' untranslated sequence, a 2040-bp open reading frame and an 895-nucleotide 3' non-coding region. In the 5' flanking region of the gene, two consensus TATA-box sequences were found. Identification of the first exon by ribonuclease-protection assays and the determination of the 5' end of Col10a-1 mRNA transcripts by primer-extension analyses show that the more 3' TATA box is probably predominantly used and that there are at least three transcription start sites in the exon 1 sequence 3' to this, resulting in 5' untranslated regions of 78, 77 and 55 nucleotides. By means of rapid amplification of cDNA ends by polymerase chain reaction, an additional mRNA species was detected which overlapped the other Col10a-1 transcripts, including the 3' TATA box sequence, giving a 5' untranslated sequence of approximately 235 bases. This latter transcript starts approximately 20 bp 3' to the more 5' TATA box. The data suggest alternative use of promoters and transcription starts for the Col10a-1 gene. Comparison of the combined nucleotide and deduced amino acid sequences of exons 2 and 3 with chicken, bovine and human collagen X genes, showed a high degree of similarity indicating conservation of this gene throughout evolution. Mouse Col10a-1 mRNA was shown to be approximately 3.0 kb and the pepsinized protein, as detected by SDS/PAGE, was approximately 45 kDa. The mRNA and protein sizes correlate with that predicted by the open reading frame. Reverse-transcription polymerase chain reaction assays indicate that the mouse collagen X gene is first expressed at 13.5 days post coitum, temporally preceding the onset of endochondral ossification. In agreement with the generally accepted association of type-X collagen with endochondral ossification, in situ hybridization analyses indicate that Col10a-1 mRNA are restricted to the hypertrophic regions of growth cartilage. PMID- 8477739 TI - The primary structures and properties of non-stomach lysozymes of sheep and cow, and implication for functional divergence of lysozyme. AB - Lysozymes were purified from the homogenate of cow and sheep kidneys, and their amino-acid sequences as well as some enzymic properties were determined. Like most mammalian lysozymes both sheep and cow kidney lysozymes are composed of 130 amino acids. The sequences of these two lysozymes are the most similar to each other (95% identity), the second most similar to the conventional mammalian lysozymes like human, rat and rabbit lysozymes (74-85% identity), and much less similar to their own stomach lysozymes (65-70% identity). Cow kidney lysozyme is also different from cow milk lysozyme (partial sequence), indicating that cow contains at least three kinds of chicken type lysozymes, that is kidney, milk and stomach lysozymes. The activities of cow and sheep kidney lysozymes were 3% and 29% against Micrococcus luteus at pH 7.0, ionic strength of 0.1 and 30 degrees C, and 57% and 84% against glycol chitin at pH 5.5 and 40 degrees C, which were expressed as percentages relative to hen lysozyme. The net charges of cow and sheep lysozymes at pH 7 were less positive (+1.5 and +2.5, respectively) than human and hen lysozymes (both +8.0) and rather close to the stomach ones (-2 to 0). The decreased net positive charge observed in cow and sheep kidney lysozymes may suggest that the ruminant kidney lysozyme had functioned once as a digestive enzyme in the stomach of an ancestral ruminant. PMID- 8477740 TI - Identification of novel phosphorylation sites in murine A-type lamins. AB - We report the distribution of phosphorylation sites in murine lamins A and C (A type lamins) in vitro and in vivo followed by reverse-phase high-performance liquid chromatography and microsequencing of peptides spanning the almost complete lamin sequence. We show that two distinct protein kinases, cell-division cycle-2 kinase (cdc2 kinase) and protein kinase C (PKC), phosphorylate murine A type lamins at the non-alpha-helical amino- and carboxy-terminal domains in vitro and in vivo. Cdc2 kinase, but not PKC, is capable of inducing depolymerization of the nuclear lamina in permeabilized cells. Accordingly, lamins were proposed to be direct in vivo substrates of cdc2 kinase and PKC with different effects on the lamina dynamics. Analysis of the original A-type lamins revealed phosphorylation of residues Ser5 and Ser392. Residue Ser392 was substoichiometrically phosphorylated in the substrate and by cdc2 kinase in vitro. PKC phosphorylated peptides with its kinase-specific motifs surrounding Ser5, Thr199, Thr416, Thr480 and Ser625. In vivo, a mitosis-specific phosphorylation at the cdc2-kinase specific phosphoacceptor site Ser392 and of the N-terminal peptide was identified. An interphase-specific phosphorylation at Ser525 matching the PKC consensus sequence and of peptides phosphorylated by unknown kinases was determined. The results lead us to propose that different cyclin-dependent kinase activities act as lamin kinases in mitosis and in interphase. Other kinases may cooperate with cdc2 kinase during reversible disassembly in mitosis and may modulate the supramolecular assembly of lamin filaments. PMID- 8477741 TI - Orthorhombic crystal structure of the A-DNA octamer d(GTACGTAC). Comparison with the tetragonal structure. AB - The X-ray crystal structure of the double-helical A-DNA octanucleotide d(GTACGTAC) has been solved by molecular replacement and refined to a resolution of 0.219 nm. The final R-factor is equal to 16.1% for 1516 observed reflections with F > 4 sigma(F). The sequence crystallizes as an A-DNA-type double helix in the orthorhombic space group P2(1)2(1)2, with one duplex molecule solvated by 66 water molecules in the asymmetric unit. Cell parameters are a = 3.860 nm, b = 5.082 nm, c = 2.174 nm. It is the first time that such a crystal form has been observed. This orthorhombic structure has been compared with the tetragonal structure of the same oligonucleotide. It adopts a bent structure with an unusual packing between symmetry-related molecules. PMID- 8477742 TI - Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains. AB - Using the polymerase chain reaction to study mRNA expressed in human epithelial tumor cells, a member of a new family of protein kinases was identified. The catalytic domain of this kinase has amino-acid-sequence similarity to both the Tyr-specific and the Ser/Thr-specific kinase classes. Clones representing two members of this new family have been isolated from a human colonic epithelial cDNA library and sequenced. The predicted amino-acid sequences of these clones reveal that, in addition to the unusual nature of their kinase catalytic domains, they contain two Leu/Ile-zipper motifs and a basic sequence, near their C termini. As they possess domains associated with proteins from two distinct functional groups, these kinases have been named mixed-lineage kinases (MLK) 1 and 2. mRNA from MLK1 has been found to be expressed in epithelial tumor cell lines of colonic, breast and esophageal origin. The MLK1 gene has been mapped to human chromosome 14q24.3-31. PMID- 8477743 TI - Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V1a vasopressin receptor. AB - We have designed and synthesized a linear peptide analogue of arginine vasopressin. This peptide, [1-phenylacetyl, 2-O-methyl-D-tyrosine, 6-arginine, 8 arginine, 9-lysinamide]vasopressin (PhAcALVP), has a lysinamide residue substituted for the more usual glycinamide at position 9. Derivatization of PhAcALVP at the N epsilon-lysyl amino group with N-hydroxysuccinimide esters of aminomethylcoumarin (Mec) and biotin (Btn) produced the bifunctional ligands PhAcAL(Mec)VP and PhAcAL(Btn)VP, respectively. Pharmacological characterization of these peptides revealed that all were high-affinity V1a-selective antagonists. PhAcAL(Btn)VP can simultaneously bind to both the rat liver V1a receptor and avidin conjugates. Using this strategy, we were able to study the distribution of V1a receptors on the surface of the rat mammary tumour cell line, WRK-1. Routine epifluorescent microscopy and confocal image analysis were used to observe the distribution of avidin-Texas-Red associated with receptor-bound PhAcAL(Btn)VP. We conclude that PhAcALVP is a useful precursor for the production of hetero bifunctional V1a-selective ligands. Both PhAcAL(Mec)VP and PheAcAL(Btn)VP can be used selectively to probe the V1a receptor and will be versatile tools for a variety of histocytochemical applications, including receptor localization and purification. PMID- 8477744 TI - Conversion of fructose to glucose in the rabbit small intestine. A reappraisal of the direct pathway. AB - Gopher et al [Gopher, A., Vaisman, N., Mandel, H. & Lapidot, A. (1990) Proc. Natl Acad. Sci. USA 87, 5449-5453] recently reported that about 50% of the glucose formed from [U-13C]fructose infused nasogastrically in children contained 13C3 adjacent to 13C4. Assuming a high isotopic dilution of the triosephosphate pool, the authors concluded that about 50% of the fructose converted to glucose in liver and intestine bypassed the classical aldolase pathway, utilizing a hypothetical direct pathway that would involve the phosphorylation of fructose 1 phosphate to fructose 1,6-bisphosphate. The present work was undertaken in order to establish to what extent the conversion of fructose to glucose in the intestine could account for this unexpected isotopic distribution. The technique of everted sleeves was used to define the rate of conversion of [U-14C]glucose and [U-14C]fructose in the small intestine of 24-h-fasted rabbits. It appeared that, at the low concentration of fructose used by Gopher et al., almost as much fructose was converted to glucose as remained unmodified in the tissue. Fructose uptake was not inhibited by glucose, and the presence of all the necessary enzymes in the tissue indicated that the fructose to glucose conversion occurred by the aldolase pathway. Remarkably, this conversion operated with an isotopic dilution not exceeding 25%, due to the low rate of glucose metabolism and the near absence of gluconeogenesis from lactate. It can, therefore, be postulated that, in the presence of pure [U13C]fructose, the triosephosphate pool is highly enriched in 13C with little dilution by 12C, essentially giving rise to [U 13C]glucose, as reported by Gopher et al. There is, therefore, no need to postulate the participation of a direct pathway. PMID- 8477745 TI - Vigilin is a cytoplasmic protein. A study on its expression in primary cells and in established cell lines of different species. AB - A fusion protein composed of about two vigilin domains and beta-galactosidase was used to raise polyclonal antibodies which were affinity-purified and employed for immunoblotting and immunohistochemistry. A protein of an apparent molecular mass of 155 kDa could be stained in extracts of a variety of cells from different species and organs. Immunohistological studies on single cells showed that vigilin is accumulated in the cytoplasm. During in vitro maintenance of primary cell cultures, as well as of a growth-factor-dependent cell line, vigilin expression decreases and ceases in senescent cells. In contrast, vigilin is constitutively expressed in all other transformed cell lines of various origin studies so far. Vigilin expression can be induced in peripheral blood lymphocytes by mitogen stimulation. These observations suggest an involvement of vigilin in processes of cell activation. Immunoblot experiments demonstrating the presence of vigilin in a broad range of eukaryotes, indicate a high degree of evolutionary conservation. PMID- 8477746 TI - Crystal structure of apo-neocarzinostatin at 0.15-nm resolution. AB - The three-dimensional structure of apo-neocarzinostatin, an antitumour antibiotic protein isolated from Streptomyces carzinostaticus, has been determined by X-ray diffraction at 0.15-nm resolution and refined to R = 17.2%. The crystal structure of neocarzinostatin is similar to that of the related proteins actinoxanthin and macromomycin. It is also in good agreement with the solution structure determined by NMR spectroscopy. The protein molecule consists of a seven-stranded antiparallel beta-sandwich and a smaller lobe formed by two beta-ribbons. A deep cleft between the two lobes is a putative chromophore binding site. Side chains of Trp39, Leu45, Phe52, Phe78 and the disulphide Cys37-Cys47 aligning the binding cleft in neocarzinostatin suggest the importance of hydrophobic interactions in stabilizing the chromophore molecule. Comparison of the atomic models of neocarzinostatin, actinoxanthin and macromomycin reveals functional residues which might determine specificity towards different chromophores. PMID- 8477747 TI - Functional domains in the Escherichia coli release factors. Activities of hybrids between RF-1 and RF-2. AB - Chimeras between Escherichia coli release factors RF-1 and RF-2 have been constructed to study the role of the release factors in termination, in particular whether each possesses specific domains for recognition of the stop codon, and for facilitating peptidyl-tRNA hydrolysis. One hybrid factor showed normal codon-recognition activity but was defective in its ability to facilitate hydrolysis. Overexpression of this protein was toxic to the cell. Conversely, another hybrid factor showed complete loss of codon recognition but retained some hydrolysis activity. These two functional activities of the release factors were not localised in domains within either the amino-terminal or carboxy-terminal halves of the primary sequence as previously predicted. Evidence from the activities of the hybrid proteins and from earlier studies suggests that a combination of residues from the beginning and middle of the sequence, including a region of very high sequence conservation, contribute to the hydrolysis domain, whereas residues from both the amino-terminal and carboxy-terminal halves of the molecule are important for the codon recognition domain. PMID- 8477748 TI - Are there different water requirements in different steps of a catalytic cycle? Hydration effects at the E1 and E2 conformers of sarcoplasmic reticulum Ca(2+) ATPase studied in organic solvents with low amounts of water. AB - The Ca(2+)-ATPase from sarcoplasmic reticulum was transferred in an active form to a low-water system composed of toluene, phospholipids, and Triton X-100 (TPT). The Ca(2+)-ATPase activity in the TPT system with 4.0% water (by vol. was about 50% of the activity observed in all-aqueous mixtures. Phosphate formation was linear with time up to 20% of ATP hydrolysis and, as expected from an enzyme catalysed reaction, activity was linear with protein concentration. No ATPase activity was detected in the presence of 3 mM EGTA, indicating that the enzyme retained its Ca2+ dependence in the TPT system. A hyperbolic response to ATP concentration was observed with a Km of 0.15 mM. There was no detectable ATPase activity at water concentrations below 1.5% (by vol.). With 2.0% water, activity became detectable and increased as the water content was progressively raised to 7.0% (by vol.). Higher amounts of water produced unstable emulsions. Enzyme phosphorylation by ATP and dephosphorylation took place in the TPT system. The velocities of both enzyme phosphorylation and dephosphorylation increased with increments in the water content. The enzyme could also be phosphorylated in the TPT system by inorganic phosphate. However, in comparison to ATP, phosphorylation by phosphate took place with significantly lower amounts of water. It is suggested that at low amounts of water, the enzyme is in a relatively rigid conformation and, as the water content is increased, the ATPase acquires more flexibility and, hence, the capacity to carry out catalysis at higher rates. Nevertheless, the release of conformational constraints of the catalytic site of the E2 conformer takes place at water concentrations much lower than those needed for the expression of catalytic activity by the E1 conformer. PMID- 8477749 TI - The action of Trypanosoma cruzi trans-sialidase on glycolipids and glycoproteins. AB - Addition of sialic acid residues in the human pathogen Trypanosoma cruzi glycoconjugates is mediated by a trans-sialidase and not by a CMP-sialic acid:glycoconjugate sialyltransferase. Incubation of trans-sialidase with N [galactose-14C]acetyllactosamine and O-linked oligosaccharides, N-linked glycopeptides (both obtained from fetuin) or sialyllactose showed that the last three compounds were donors of sialic acid residues to the first one. Moreover, N and O-linked oligosaccharides in asialofetuin and asialomucin, respectively, served as acceptors of sialic acid units. Gangliosides GM3, GD1a and GT1b but not GM2, GM1a nor GD1b donated sialic acid units to N-acetyllactos amine when incubated with trans-sialidase. This showed that only sialic acid units bound to terminal galactosyl residues were transferred. GM1a was converted to GD1a, and GD1b to GT1b when incubated with the appropriate donor. The fact that asialo-GM1a was converted to a ganglioside migrating as GD1a on thin-layer chromatography suggested that sialic acid units may be transferred to internal galactosyl residues, although once linked to those residues they can not be further transferred to other glycoconjugates. Sialic acid residues linked alpha 2,3- but not alpha 2,6- or alpha 2,8- were transferred by the trans-sialidase. Methyl beta galactoside but not methyl alpha-galactoside served as acceptor of sialic acid units, thus suggesting that terminal alpha-linked galactosyl units in T. cruzi and mammalian glycoproteins are not sialylated by the enzyme. As the trans sialidase employed in these experiments has been shown to be located on the external surface of the parasite and to be shed to the medium, the relatively broad specificity shown by the enzyme with respect to protein- and lipid-linked oligosaccharides strongly suggests that infection by T. cruzi might alter the sialic acid distribution in glycoproteins and glycolipids of the mammalian host. PMID- 8477750 TI - CaBP2 is a rat homolog of ERp72 with proteindisulfide isomerase activity. AB - Ca-binding protein 2 (CaBP2) has been described previously as an intracisternal calcium-binding microsomal glycoprotein. We report now the primary sequence of this protein as deduced from the corresponding cDNA. The protein possesses a C terminal -KEEL retention sequence and three repeats of the thioredoxin-like motive -EFYAPNCGHCK-, and represents the rat homolog of ERp72. In contrast to earlier reports on ERp72, CaBP2 possesses significant proteindisulfide isomerase activity. Furthermore, in contrast to ERp72, CaBP2 is a glycoporotein containing O-linked glycans. The amount of CaBP2 in H-35 Reuber hepatoma cells increases in parallel with that of immunoglobin heavy-chain-binding protein under conditions which lead to impaired glycosylation, while the amount of calreticulin, another KDEL-containing glycoprotein, remains almost unchanged. PMID- 8477751 TI - Crude liver membrane fractions and extracellular matrix components as substrata regulate differentially the preservation and inducibility of cytochrome P-450 isoenzymes in cultured rat hepatocytes. AB - The influence of cell-substrata interactions on the preservation of basal or in vivo-induced microsomal cytochrome P-450 isoenzyme contents in cultured rat hepatocytes and on the adaptive responses after exposure to phenobarbital or 3 methylcholanthrene in vitro, was investigated. Hepatocytes from untreated or phenobarbital-treated rats were cultured in serum-free, aprotinin-supplemented culture medium in 96-well microtiter plates coated with collagen type I (COL), laminin, fibronectin or crude liver membrane fractions/collagen type I (CMF/COL). Basal cell functions were characterized by measuring the total protein content and lactate dehydrogenase release. The relative contributions of CYP1A1/2, CYP2B1/2, CYP2C6, CYP2C11, CYP3A and CYP4A isoenzymes were determined with ELISA using monoclonal antibodies raised against purified cytochromes P-450 from rat liver microsomes. The characterization of the CMF revealed that contaminations with mitochondria, nuclei and lysosomes are relatively low. Among these, membranes derived from the endoplasmic reticulum appeared to be the major organelle contaminant of the CMF. The matrix components laminin, fibronectin and collagen type IV were found in appreciable amounts. Hepatocytes from untreated rats, cultured for up to nine days on CMF/COL-coated plates, retained their relative cytochrome P-450 contents at 1.5-3-fold higher levels when compared to cells cultured on COL, fibronectin or laminin. Similarly, hepatocytes from phenobarbital-treated rats preserved the contents of barbiturate-inducible CYP2B1/2 and CYP3A proteins best when cultured on CMF/COL. After exposure of hepatocytes cultured on CMF/COL to phenobarbital from days 3-6, CYP3A proteins were enhanced more than twofold and CYP2B1/2, depending on the exposure level, increased 1.3-6-fold. After exposure to 3-methylcholanthrene, a threefold increase of CYP1A proteins was found in CMF/COL and laminin cultures. These results indicate that CMF/COL, as a substratum in rat hepatocyte cultures, regulates gene expression of cytochromes P-450 isoenzymes for up to 9 days and provides a matrix which enables the cells to respond qualitatively similar to the response observed in different zones of the liver. This activity cannot be replaced by single-matrix components. PMID- 8477752 TI - High-mobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse. AB - Exhaustive extraction of mouse tissues with perchloric acid has been used together with reverse-phase HPLC and electrophoresis to quantify the amounts of chromosomal proteins HMG17, HMG14 and HMGI, relative to histone H1. Normal lung and thymus contain approximately 3% HMG17/HMG14 but only approximately 2% HMGI. In tumor tissues (Lewis lung carcinoma and lymphoma NQ35), the amount of HMG17/HMG14 is not greatly altered but HMGI levels rise considerably, reaching 10% in Lewis lung carcinoma. HMGI synthesis does not replace HMG17/HMG14 proteins, suggesting that HMGI proteins contribute to the structure of chromatin regions in a manner distinct from those of HMG17/HMG14. Ion-spray mass spectrometry has been used to determine the molecular masses of H1 subtypes from the same four mouse tissues. In addition to the six known species H1 zero, H1a, H1b, H1c, H1d and H1e, a newly defined subtype of mass 21,756 Da from Lewis lung carcinoma, named H1L was identified. Several phosphorylated H1 subtypes have also been defined by mass spectrometry. The combined use of reverse-phase HPLC and electrophoresis permitted quantification of these seven histone H1 subtypes in the four mouse tissues. Increased phosphorylation of H1 subtypes in tumors parallels the phosphorylation of HMGI proteins which are present in great amounts, showing that both are involved as post-translational-modified forms in the structure of the chromatin of neoplastic systems. PMID- 8477753 TI - Natural cycloheximide resistance in yeast. The role of ribosomal protein L41. AB - The yeast Kluyveromyces lactis is resistant to high concentrations (1 mg/ml) of the antibiotic cycloheximide. Using in vitro translation studies it was confirmed that this extreme resistance is a property of ribosomes. The resistance determinant from K. lactis was cloned into Saccharomyces cerevisiae. Nucleotide sequence analysis of the determinant demonstrated that resistance was conferred by the K. lactis ribosomal protein L41. K. lactis was shown to contain only one copy of the gene that encodes this protein and the gene was located to chromosome III. In contrast, S. cerevisiae was found to contain multiple copies of the gene for the corresponding ribosomal protein L41 which mapped to two of the three chromosomes V, XIV and VIII. Since the cycloheximide-resistance gene of K. lactis causes essentially complete protection against inhibition by the drug, it is likely to be particularly useful as a selective marker in eukaryotic gene transfer studies. PMID- 8477754 TI - Two different genes from Schwanniomyces occidentalis determine ribosomal resistance to cycloheximide. AB - Two genes (SCR1 and SCR2) encoding natural cycloheximide resistance in the budding yeast Schwanniomyces occidentalis have been cloned by expression in Saccharomyces cerevisiae. Both genes determine resistance to the inhibitory action of cycloheximide on the ribosome, SCR1 and SCR2 are present as single copies in Schwanniomyces occidentalis, where they map on chromosomes II and V, respectively. The nucleotide sequence of SCR2 contains an open reading frame of 321 nucleotides which is interrupted by an intron of 452 nucleotides. It encodes a polypeptide of 106 amino acids of molecular mass 12.25 kDa and pI 11.19. The deduced amino acid sequence shows a high degree of similarity to the L41 protein of the 60S ribosomal subunit from several eukaryotic organisms. The intron and the 5' non-coding region of SCR2 possess conserved elements which are typical of yeast ribosomal protein genes. A single amino acid change determines the resistance or sensitive phenotype to cycloheximide of the 80S ribosome since replacement of Gln56 in L41 from Schwanniomyces with Pro, by site-directed mutagenesis, confers cycloheximide sensitivity. SCR2 may serve as a practical yeast cloning marker if integrated in a multicopy plasmid. PMID- 8477755 TI - A 1H-NMR study of the transcription factor 1 from Bacillus subtilis phage SPO1 by selective 2H-labeling. Complete assignment and structural analysis of the aromatic resonances for a 22-kDa homodimer. AB - 1H-NMR experiments have been performed on transcription factor 1 (TF1) encoded by Bacillus subtilis phage SPO1. To study this 22-kDa homodimeric DNA-binding protein, a selective 2H-labeling strategy has been employed. Complete sequence specific assignments of all the resonances from the five aromatic residues were determined by a modified standard sequential-assignment procedure. The reduced contribution of spin diffusion upon the long-mixing-time nuclear-Overhauser enhancement spectroscopy for the selectively 2H-labeled variants, as opposed to the fully 1H-containing protein, has allowed for the identification of the spin systems and of the long-range dipolar contacts between Phe28 and Phe47 protons in the protein core and between Phe61 and Phe97 protons. The latter suggests an interaction between the proposed beta-ribbon DNA-binding arm and the carboxy terminus of the paired monomer. A previously proposed TF1 structural model [Geiduschek, E. P., Schneider, G. J. & Sayre, M. H. (1990) J. Struct. Biol. 104, 84-90)] has been modified using constrained-energy-minimization calculations incorporating the experimentally determined set of aromatic-to-aromatic contacts. This new model has been analyzed with regard to the relative mobility and the relative solvent accessibility of the aromatic residues which have been measured by the nonselective T1 relaxation times of the aromatic resonances for the fully 1H-containing protein and the relaxation time enhancements upon selective 2H labeling, respectively. PMID- 8477756 TI - LymnaDFamides, a new family of neuropeptides from the pond snail, Lymnaea stagnalis. Clue to cholecystokinin immunoreactivity in invertebrates? AB - Five tridecapeptides have been identified from the central nervous system of the pond snail, Lymnaea stagnalis. The sequences are Pro-Xaa-Asp-Arg-Ile-Ser-Yaa-Ser Ala-Phe-Ser-Asp-Phe. NH2, where Xaa is either Tyr or Phe and Yaa either Asn, Ser or Gly. The peptides are named lymnaDFamides to acknowledge identity with the C terminal dipeptide of the mammalian neuropeptides, cholecystokinin (CCK) and gastrin. They were detected by an antiserum that recognizes the biologically active C-termini of cholecystokinin and gastrin. LymnaDFamide-1 (Xaa = Tyr and Yaa = Asn) had no effect on trout gallbladder, which responds equally to CCK and gastrin. We propose that the lymnaDFamides belong to an Asp-Phe-amide superfamily, which includes CCK and gastrin, and suggest that the widespread CCK/gastrin immunoreactivity in invertebrates is due to peptides belonging to such a superfamily. PMID- 8477757 TI - Genetic control of population structure in heterogeneous strains of methicillin resistant Staphylococcus aureus. AB - Cultures of heterogeneous strains of methicillin resistant Staphylococcus aureus are composed of several subpopulations of cells that differ in their level of antibiotic resistance and frequencies. Experimental evidence is presented indicating that the number of these subpopulations, their resistance level and the frequency with which they are represented in a culture are strain-specific and reproducible with a surprising degree of precision from one culture to another. This implies a genetic control of population structure in these bacteria. PMID- 8477758 TI - Importance of beta-lactamase induction. AB - Induction of an enzyme is a temporary phenomenon in which the rate of enzyme synthesis is greatly increased in response to the presence of an inducer in the environment. Induction of beta-lactamase synthesis is important for the resistance of staphylococci to penicillins since the drug both induces synthesis of the enzyme and is hydrolysed by it. Similarly, some compounds both strongly induce and are hydrolysed by the chromosomally-determined beta-lactamases of gram negative bacilli (e.g. amoxicillin and cefoxitin for Enterobacter cloacae). Other compounds (e.g. piperacillin and cefotaxime) although labile are poor inducers, so that in the case of these drugs the phenomenon of induction is not important but the presence of the enzyme is, since resistant mutants with genetically derepressed synthesis of the enzyme can emerge. Induction can also be important when a strong inducer is present with a poor inducer and antagonises the activity of the latter. PMID- 8477759 TI - Relevance of antibiotic susceptibility testing for clinical practice. PMID- 8477760 TI - Anatomical barriers for antimicrobial agents. AB - It is often suggested that there are substantial anatomic barriers to the passage of antibiotics from the circulation into tissues and fluids of the body. In fact, most capillary beds are fenestrated and allow the passage of antimicrobial agents into tissue fluids fairly readily. At equilibrium, the mean concentrations of free (unbound) antibiotic in plasma and tissue fluids over the dosing interval are equal. However, the time to achieve equilibrium may range from minutes to days, depending on the ratio of surface area to volume of the tissue fluid compartment. There are several sites in the body in which nonfenestrated capillary beds pose appreciable barriers to the diffusion of antibiotics, namely the central nervous system, the eye and the prostate gland. Only lipid-soluble drugs traverse these capillaries readily. If the nonporosity of the capillaries were the only barrier to drug diffusion in these sites, the mean concentrations would eventually be equal to those in the plasma. However, in the central nervous system and the retina of the eye, transport pumps for organic anions combine with the effect of nonporous capillaries to produce concentrations which, even at equilibrium, are lower than those in the plasma. Bulk flow may also play a role in lowering drug concentrations in the cerebrospinal fluid. In the prostate gland, pH partition may cause mean concentrations in the prostatic secretions to differ from those in the plasma at equilibrium. PMID- 8477762 TI - Fungal and bacterial infections in the immunocompromised host. AB - As the number of immunocompromised patients increases due to the spread of the AIDS epidemic and the successes being achieved with transplantation, cancer chemotherapy and immunosuppressive therapy, increased attention is being turned to the prevention and treatment of the infections that afflict these individuals. The risk of infection in these patients is determined by the interaction between the epidemiologic exposures that the patient experiences and the net state of immunosuppression (the greater the exposure, the greater the chances of infection even in an immunologically competent individual; the greater the net state of immunosuppression, the greater the chances of infection even with minimal exposures). The bacterial and fungal infections that affect these patients are reviewed and strategies of antimicrobial management defined, recognizing that there are three modes of use of antimicrobial agents in these patients: therapeutic administration to treat clinical infection, and prophylactic and pre emptive administration to prevent or abort clinical infection. These last two are of particular importance in this patient population because the prime aim of the infectious disease clinician in dealing with these problems is the prevention of clinical disease. PMID- 8477761 TI - Diseases and drug-related interventions affecting host defence. AB - Recognition of an impaired immune system has implications for the diagnosis, treatment and outcome of infections. Not only the type of immunological dysfunction but also the degree of the dysfunction is important. A review is presented of the systemic diseases and immunosuppressive agents which may result in defects in host defence and associated infections. Especially in transplant patients and patients with HIV infection, knowledge of the stage of the host defense defect is important for the success of prophylactic regimens and for the clinical approach in the event of infection. PMID- 8477764 TI - Relevance of animal models for clinical treatment. AB - The use of animal models has become an integral part of the evaluation of drugs for antimicrobial chemotherapy. Animal models can be used to define the penetration of antimicrobial agents at foci of infections, the time course of in vivo antimicrobial therapy, dose-response relationships, and the influence of therapy on the pathophysiologic consequences of infection. Animal models have been useful in the delineation of many of the basic principles currently used in clinical practice and in the selection of new agents and new therapeutic approaches for clinical trials in humans. In spite of the many positive aspects of animal models, several problems, such as altered pharmacokinetics in animals, can preclude direct application of results to clinical practice. Studies in animal models cannot replace the need for human clinical trials. PMID- 8477763 TI - The value of new antimicrobial agents. AB - New antimicrobial agents require careful assessment to determine whether they possess the appropriate properties for clinical use. Many new compounds of value in the prophylaxis and therapy of infections have been included in the current armamentarium. Close monitoring to identify possible adverse effects of new agents is essential. Alternative uses of older agents also expands therapeutic opportunities in the combat against infectious diseases. Inappropriate use of antimicrobial agents contributes to the worldwide problem of increasing bacterial resistance. The dramatic spread of such bacterial strains is partially responsible for the rising costs of infectious diseases. A rational and strict antibiotic policy is thus of great importance for the optimal use of these agents. PMID- 8477765 TI - Abnormal pharmacokinetics: the need for monitoring. AB - Optimal use of a drug depends on rational dosing and subsequent therapeutic drug monitoring for effectiveness and toxicity. Drug monitoring is not relevant for all drugs, but is indicated in the case of drugs which have a narrow therapeutic range or show a large inter-individual variation. If the response is not satisfactory or toxic side effects are observed, the regimen has to be adjusted or another drug used. Methods have been developed to establish rational dosing schedules for the individual patient. In previous methods, the patient's specific data such as age, length, weight and serum creatinine are integrated with population pharmacokinetic parameters for a drug. This approach is subject to an appreciable margin of error, particularly in patients whose physiology is far from normal. Therapeutic drug monitoring via blood level determination makes it possible to evaluate the patient's individual pharmacokinetic parameters on which a rational dosage regimen can be based. PMID- 8477766 TI - Pharmacodynamics of antimicrobial agents as a basis for determining dosage regimens. AB - Pharmacodynamic parameters, such as the rate of bactericidal activity with increasing drug concentrations, post-antibiotic effect, sub-MIC effects, post antibiotic leukocyte enhancement and first-exposure effect, more accurately describe the time course of antimicrobial activity than the MIC and MBC. Aminoglycosides and quinolones exhibit concentration-dependent killing and induce prolonged post-antibiotic effects. The amount of drug rather than the dosing frequency determines the efficacy of these drugs. However, high peak levels can reduce the emergence of resistance, and once-daily dosing of aminoglycosides can also reduce nephrotoxicity and ototoxicity. On the other hand, beta-lactam antibiotics show time-dependent killing and produce prolonged post-antibiotic effects only with staphylococci. The frequency of drug administration is an important determinant of outcome for these drugs, as the duration of time serum levels exceed the MIC is the major determinant of efficacy. PMID- 8477767 TI - Liposomes as carriers of antimicrobial agents or immunomodulatory agents in the treatment of infections. AB - Targeting of antimicrobial agents by means of liposomes is under investigation and may be of importance in the treatment of infections that prove refractory to conventional forms of antimicrobial treatment. The ability to achieve a significantly longer residence time of liposomes in plasma and limited uptake of liposomes by the mononuclear phagocyte system opens up new areas of investigation and potential therapeutic application. By manipulating the liposomal composition, rates of uptake and intracellular degradation can be influenced and thereby the rates at which liposome-encapsulated agents are released and become available to exert their therapeutic action. With respect to the targeting of macrophage modulators at the mononuclear phagocyte system by means of liposomes for maximal stimulation of the nonspecific antimicrobial resistance, experimental evidence is now available of the potential usefulness of liposomes as carriers of these agents. This approach may also be of importance for the potentiation of treatment of severe infections. PMID- 8477768 TI - Role of glucocorticosteroids in the treatment of infectious diseases. AB - The role of glucocorticosteroids in the management of infectious diseases in man remains controversial, although experimental data obtained both in in vitro systems and in experimental infections in animals provide evidence of a beneficial effect of such treatment. Their use in the treatment of Pneumocystis carinii pneumoniae and severe typhoid fever seems indicated. A beneficial effect on the treatment of bacterial meningitis needs to be confirmed. Sufficient data are now available that argue against steroid treatment in septic shock. However, new treatment modalities such as monoclonal antibodies against endotoxin and inflammatory mediators are currently being developed to modulate infectious inflammation. This could also bring a renaissance of the role of glucocorticosteroids in the treatment of infectious diseases. PMID- 8477770 TI - Epidemiological and clinical aspects of carcinoma in situ of the testis. AB - Despite the high cure rate in men with testicular cancer, efforts should be made to diagnose the disease at the preinvasive stage. The disease, which affects young males, is potentially lethal. Furthermore, testicular neoplasia diagnosed at the stage of CIS can be cured without the negative impact on the life-quality of the survivors, as chemotherapy and other systemic treatment can be avoided. The treatment of choice is orchidectomy if the neoplasia is unilateral, or localized irradiation in bilateral cases. Testicular biopsy performed after puberty is at present the only reliable diagnostic method. Screening for CIS in the contralateral testis should be offered to men with unilateral testicular cancer. Patients with assumed extragonadal germ cell tumour and intersex individuals are also recommended to have a biopsy for CIS. Biopsies should also be considered in adults with maldescended testes and in selected cases of infertility. In the future the techniques of detecting of CIS cells in semen may become refined. In such circumstances, the general male population may be targeted for screening and more cases of testicular cancer could then be prevented. PMID- 8477769 TI - Interleukin-1 as a possible agent for treatment of infection. AB - Treatment of experimental animals with bacterial products, such as cell wall components of gram-negative bacteria, leads to enhanced resistance to a variety of microorganisms. Since interleukin-1 and other pro-inflammatory cytokines are induced by such bacterial products, it has been investigated whether these cytokines are also capable of enforcing host resistance. It has been possible to demonstrate that a low dose of interleukin-1 protects mice against death from either gram-negative or gram-positive bacteria, Candida albicans and Plasmodium berghei. The protection against lethal bacterial and fungal infection can be produced in both normal and neutropenic animals. Despite extensive investigations, the mechanism of protection is not understood. A possible mechanism, which is currently being investigated, is that interleukin-1 interferes with the deleterious action of the pro-inflammatory cytokines during the lethal phase of the infection. PMID- 8477771 TI - Risk factors for carcinoma in situ of the contralateral testis in patients with testicular cancer. An interim report. AB - In a study aimed at evaluating risk factors for carcinoma in situ (CIS) in the contralateral testis of selected patients with testicular cancer, information from 89 patients who have had contralateral testicular biopsies is available. The biopsies were performed because of the coexistence of the previously established risk factors - atrophy of the remaining testis, or a history of maldescent. CIS was diagnosed in 13% of patients, the prevalence being the same for both open and needle biopsies. Compared to its overall prevalence in the contralateral testis in testicular cancer an increased risk of CIS has been found in clinically atrophic testes but has not been found for maldescent. Patients found to have CIS were younger than those in whom it was not detected. PMID- 8477772 TI - Should the contralateral testis be biopsied? Round table discussion. AB - Testicular tumours are bilateral in 5.2% of cases although the incidence of bilaterality is affected by the mode of treatment of the primary tumour. A biopsy of the contralateral testis of testicular tumour patients will reveal carcinoma in situ in 5.5% of cases. In Denmark, most testicular tumour patients have a contralateral biopsy at the time of the primary orchidectomy, but in many countries general urologists and surgeons are not always aware of the advantages of simultaneous contralateral biopsy. Some specialist centres perform a contralateral biopsy as a secondary procedure once the patient has been referred. It has not been the policy in USA to take a contralateral biopsy at the initial orchidectomy, nor to offer a biopsy to patients after referral to a specialist centre. As a result of the discussions at this conference, urologists in USA will now be encouraged to take a contralateral biopsy at the time of initial surgery. If this is not performed, patients should be offered a biopsy after a full discussion of the advantages and possible side effects of the procedure so that informed consent can be given. PMID- 8477773 TI - Effects of chemotherapy and radiotherapy on spermatogenesis. AB - Radiation and chemotherapy reduce sperm count and cause infertility in males. In the mouse, rat, and human, the differentiating spermatogonia are the most sensitive to killing by cytotoxic agents, resulting in short-term azoospermia. Stem spermatogonia are also killed by some agents. In the mouse, sperm production gradually recovers from surviving stem cells without a lag period. In the rat, however, surviving stem cells may remain as A spermatogonia for long times without initiating differentiation. In humans, there may be a long period of azoospermia; the time at which recovery or sperm production is initiated appears to be related to the degree of stem cell killing. Knowledge of the mechanisms regulating spermatogonial proliferation and differentiation could lead to ways to minimize the duration of azoospermia following treatment. PMID- 8477774 TI - Protection against cytotoxic-induced testis damage--experimental approaches. AB - In animal models the possibility has been explored that pharmacological inhibition of cell division in the spermatogenic epithelium during cytotoxic treatment for cancer would preserve fertility. Recent animal models are reviewed. In the rat, gonadotrophin releasing hormone (GnRH) analogues or a combination of a progestogen and an androgen will protect spermatogenesis from the cytotoxic and mutagenic effects of procarbazine and radiation. Cyclophosphamide toxicity is not alleviated by GnRH treatment. In the mouse, a GnRH analogue was ineffective against cisplatin testicular toxicity. Complete suppression of the spermatogenic process does not seem to be important for a successful outcome. These experiments serve to illustrate the inconsistency between different laboratories. However, it is argued that once the correct pharmacological approach and the mechanisms have been established in animal models, only then will it be possible to predict the efficacy of these adjuvant treatments to preserve fertility in men being treated for cancer. PMID- 8477775 TI - The role of LHRH-analogues in protecting gonadal functions during chemotherapy and irradiation. AB - Therapeutic success has focused attention on late effects in patients with testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, and acute leukaemia. Since most patients with testicular cancer are young, the impact of cytotoxic chemotherapy on fertility and hormone deficiency has become particularly important. It has been shown that pulsatile secretion of luteinizing hormone releasing hormone (LHRH) is a prerequisite for normal gonadal function. In contrast, non-pulsatile, chronic treatment with supraphysiological doses of LHRH-analogues (LHRHA) results in suppression of the pituitary-gonadal axis. It has been suggested that inhibition of spermatogenesis during exposure to cytotoxic drugs might reduce gonadal toxicity. The protective effects of LHRHA during chemotherapy or irradiation has been examined in 11 preclinical studies. In only 6 out of 11 models could protection be demonstrated. Four clinical trials have been performed using LHRHA as a gonadal protector. In none of these trials could LHRHA significantly influence severity and duration of germ cell impairment. New approaches are needed to minimize or even prevent gonadal toxicity during chemotherapy or irradiation, such as reduction of courses, alternative schedules, or new drugs. PMID- 8477776 TI - A preliminary report: postoperative fertility assessment in nerve-sparing RPLND patients. AB - Nerve-sparing RPLND is a procedure suited to patients with clinical stage I nonseminoma. Additionally, nerve-sparing techniques are applicable to patients with higher stage disease. Although ejaculation is reliably preserved with nerve sparing techniques, the question of these patients' fertility has remained. Fertility was assessed in these patients by two techniques: laboratory analysis of semen and a post-RPLND questionnaire. Semen analyses and DNA histograms suggested fertility in > 70%; in addition, 43 of 53 (81%) patients who have tried to father children post RPLND have been successful. Nerve-sparing RPLND appears to be able to preserve fertility potential in these patients. PMID- 8477778 TI - The possible role of sex hormones in the development of testicular cancer. AB - The peak incidence of testicular cancer in young men suggests that gestational development and events during early infancy and puberty are important in the pathogenesis of the disease. There are two potentially significant events: the transformation of fetal germ cells into carcinoma-in-situ cells (CIS) and later conversion of CIS cells into fully invasive cancer. Several hypotheses suggest an endocrinological background to testicular neoplasia. Based on epidemiological and experimental evidence, the possible role of oestrogens, androgens and gonadotrophins is discussed in this review. The role of Sertoli cells and the importance of interplay between endocrine and paracrine factors is also stressed. PMID- 8477777 TI - Semen quality after treatment for testicular cancer. AB - During the last 14 years repeated sperm cell analyses and serum hormone analysis were done regularly in patients with testicular cancer before and after treatment. The summarized results are hereby reported. The sperm cell count was highly impaired in 60-70% of testicular cancer patients evaluated 1-4 weeks after unilateral orchidectomy before further treatment. However, improvement of the exocrine gonadal function was regularly observed during the following 2-3 years, provided there were normal or only slightly elevated pre-treatment FSH levels. Standard irradiation and cytotoxic treatment (abdominal radiotherapy 30-40 Gy; < or = 4 cycles of cisplatin-based chemotherapy) delayed this recovery by about one year. Higher doses of chemotherapy or combined irradiation/chemotherapy reduced the chances of rapid improvement of the exocrine gonadal function. Unilateral retroperitoneal lymph node dissection resulted in a slight reduction of the post treatment ejaculatory volume, even in patients with preserved antegrade ejaculation. PMID- 8477779 TI - The biology of primordial germ cells. AB - Primordial germ cells are the founder cells of the gametes. They arise at the earliest stages of development, and migrate to the genital ridges, where they join the somatic cells of the future gonad. The factors that determine their formation and migration are largely unknown. Primary culture of PGCs isolated at different times during their migration has allowed the analysis of some aspects of the control of their behaviour. The effects of culture medium conditioned by genital ridges suggested that both proliferation and migration of PGCs may be controlled in part by diffusible factors. Several purified growth factors are now known which affect PGC numbers in culture. These include positive and negative regulators of proliferation, survival factors, and chemotropic factors. During migration, PGCS must change their affinities for surrounding cells, and some aspects of this can be analysed in culture. For example, PGCs isolated at different stages in their migration show different capacities to adhere to fibronectin. PMID- 8477780 TI - Heparin binding growth factors and the control of teratoma cell proliferation. AB - The role of basic fibroblast growth factor (bFGF) in the control of teratoma cell proliferation was examined. It was found that bFGF stimulates proliferation at low concentrations but induces cell migration at higher doses. These effects could be efficiently counteracted by addition of protamine sulphate. Moreover the bFGF gene is actively transcribed in primary human testicular embryonal carcinomas but was not expressed in any other embryonic tumour examined. The biological implications of these findings will be discussed. PMID- 8477781 TI - Cultured cell lines from human teratomas: windows into tumour growth and differentiation and early human development. AB - Cultured cell lines from human teratomas provide models to study molecules which might regulate tumour growth or normal embryonic development. Here, we describe efforts to delineate the role of transcription factors, extracellular matrix, and growth factors in controlling growth and differentiation of human embryonal carcinoma and yolk sac tumour. PMID- 8477782 TI - 20/20 Analysis: taking a close look at the margins. AB - This article presents "20/20 Analysis" as an experimental, output-oriented, noncategorical alternative to traditional approaches to identification of students for special education. 20/20 Analysis identifies students showing least (below 20th percentile) and most (above 80th percentile) progress toward important objectives of education in a school. The situation of each student in low 20% and high 20% groups is then examined as a basis for broad (noncategorical) approaches to improvement of learning opportunities. Case studies of two schools are present. Policy implications are considered briefly. PMID- 8477783 TI - Teaching preschool children with disabilities to respond to the lures of strangers. AB - An investigation was conducted to determine the effectiveness of a constant-time delay procedure used in combination with multiple exemplars of strangers, lures, and sites to teach a generalized response to the lures of strangers to four preschool children with disabilities. Although the correct response was quickly acquired in the training site, the response failed to generalize to the probe sites until training was conducted in vivo. Instruction in vivo resulted in acquisition, maintenance, and generalization of the response to strangers' lures. Generalization occurred across probes with novel exemplars of lures, strangers, and sites. PMID- 8477784 TI - Two approaches to reading instruction with children with disabilities: does program design make a difference? AB - This study examined the effects on reading achievement of variation in program design and tested the hypothesis this Distar Reading Mastery's (Engelmann & Bruner, 1988b) demonstrated effects with disadvantaged children in Project Follow Through can be generalized to children with disabilities. We compared the effects of two synthetic phonics reading programs, Direct Instruction (DI) Reading Mastery I and II and Addison Wesley's Meet the Superkids and The Superkids' Club, (Rowland, 1982a, 1982b) for 81 children in transitional kindergarten special education classes. No significant achievement differences were evident for the instructional program either at the end of the treatment year, or on follow-up testing 1 year later. However, among children who made advanced progress, the DI group showed larger reading gains. PMID- 8477785 TI - History strategy instruction: problem-solution-effect analysis, timeline, and vocabulary instruction. AB - This multiple baseline study investigated the effectiveness of history strategy instruction emphasizing the linkage of knowledge in teaching junior high students with behavior disorders. The intervention included 24 students and 3 teachers across three classes for 3-6 weeks. The strategy included a scripted curriculum involving brisk student-teacher interchanges; student note taking and constructing of timelines and vocabulary definitions; and reciprocal questioning, using a carefully selected history textbook. Results indicate that the history strategy was effective; students in each class showed immediate and educationally significant improvement compared with baseline instruction that employed traditional history instruction. PMID- 8477786 TI - Transition from school to adulthood: case studies of adults with learning disabilities who dropped out of school. AB - In-depth, structured interviews were conducted over a 2-year period with four young adults previously identified as having learning disabilities during their school years. All four had dropped out of high school; but overall, they reported that their early withdrawal was an important and affirming choice in their transition from youth to young adulthood. Themes emerging as noteworthy include their lack of involvement in formal vocational assessment, their own individualized education programs, and adult services. The personal stories and experiences cast doubt on the prevailing opinion that school dropouts are "losers" and "failures." In contrast, their stories reveal a serious shortfall in their secondary special education programming and in the overall transition planning process. PMID- 8477787 TI - Who becomes an "at-risk" student? The predictive value of a Kindergarten Screening Battery. AB - This study was undertaken to determine whether a preschool screening instrument could predict whether kindergarten students would later be retained, referred to special education, or placed in special education. The results of Early Prevention of School Failure (EPSF) screening on 161 kindergarten students were examined. Students who had been retained, referred to special education, or placed in special education demonstrated significantly lower EPSF pretest scores except in the gross motor modality. All EPSF modalities were statistically significant predictors of students' status; however, other factors such as family support network, preschool experiences, and motivational factors must be considered in evaluating whether a student is "at risk" of later school failure. PMID- 8477788 TI - "I've counted Jon": transformational experiences of teachers educating students with disabilities. AB - The purpose of this study was to describe the experiences of general education teachers who have had a student with severe disabilities in their class. Interviews of 19 general education teachers, kindergarten through Grade 9, as well as questionnaires completed by 18 teachers, were analyzed using categorical coding procedures to identify themes related to the teachers' experiences. Results showed that despite teachers' initial negative reactions to the placement of a child with severe disabilities in their classrooms, 17 teachers described transforming experiences of a more positive nature and related many benefits to the students with disabilities, their classmates, and the teachers themselves. Respondents also characterized what support services they found helpful and not helpful. PMID- 8477789 TI - Decreased expression of the platelet-derived growth factor beta-receptor in fibroblasts from a patient with Werner's syndrome. AB - The study of Werner's syndrome, a premature ageing syndrome, may provide insight into the processes of natural ageing. We investigated the reason for the reduced growth potential of fibroblasts in Werner's syndrome which is considered to be similar to that of fibroblasts in normal senescence. The responses to different isoforms of platelet-derived growth factor (PDGF) of fibroblasts from a patient with Werner's syndrome (W-cells) and from a normal subject (control cells) were assessed by [3H]thymidine incorporation assay, a 125I-PDGF-AB binding experiment, and Northern blot analysis with a PDGF beta-receptor specific cDNA probe. PDGF stimulated increase in [3H]thymidine incorporation in W-cells was much lower than that in control cells, especially with PDGF-AB and -BB as mitogens. The specific binding of 125I-PDGF-AB to W-cells was correspondingly lower than that to control cells. Furthermore, Northern blot analysis demonstrated a decreased basal level, and lack of PDGF-AB-induced up-regulation of the PDGF beta-receptor transcript in W-cells. Decreased expression of the PDGF beta-receptor due to decrease in its synthesis may be a causative factor of the decreased mitogenic response of W cells to PDGF. PMID- 8477790 TI - Effect of glucagon immunoneutralization on the increase in urea synthesis after hysterectomy in rats. AB - To study the effect of glucagon immunoneutralization on postoperative changes of urea synthesis, hysterectomized rats were given one injection of a specific high titre antibody against pancreatic glucagon 24 h before operation raising the plasma glucagon binding capacity to values 10-20 times higher than the plasma glucagon concentration in control animals. Earlier studies have shown that the spontaneous rate of urea-N synthesis (UNSR) doubles 3 h after operation, and that the Vmax of the process, the capacity of urea-N synthesis (CUNS) is 50% higher than normal values 24 h after operation. Therefore, the effect of glucagon on UNSR and CUNS were investigated 3 and 24 h postoperatively, respectively. Control animals were given non immune rabbit serum. Glucagon immunoneutralization partly normalized the early increase in UNSR 3 h postoperatively (control: 4.7 +/- 0.3, hysterectomy+serum: 6.7 +/- 0.4, hysterectomy+Gluc-Ab: 5.5 +/- 0.4 mumol (min.100 g BW)-1), but had no effect on the increase of CUNS 24 h postoperatively (control: 7.9 +/- 0.3, hysterectomy+serum: 9.5 +/- 0.3, hysterectomy+Gluc-Ab: 9.8 +/- 0.5 mumol (min.100 g BW)-1). This shows that glucagon is important for the early postoperative increase in the efficacy of urea synthesis, whereas the late increase in capacity seems not to depend on hyperglucagonemia. PMID- 8477791 TI - Increased rates of cortisol production and urinary free cortisol excretion in elderly women 2 weeks after proximal femur fracture. AB - Cortisol production rate and urinary free cortisol excretion have been measured in healthy elderly women and elderly women about two weeks after upper femur fracture. Plasma cortisol was determined mid-morning, at the start of urine collection. All three variables were higher in the injured patients than in the control subjects. Urinary free cortisol excretion showed the greatest rise and was correlated with cortisol production rate in the patients. In the control subjects there was no correlation and nearly all the points fell below the regression line for the injured patients, indicating that urinary free cortisol excretion rose in relation to cortisol production rate after injury. Measurement of creatinine clearance showed that this was not due to an increased glomerular filtration rate, and a possible explanation is decreased metabolic clearance of cortisol. Plasma cortisol was not significantly correlated with either cortisol production rate or urinary free cortisol excretion. PMID- 8477792 TI - Binding of cyclosporine by erythrocytes: influence on cell shape and deformability. AB - Cyclosporine is a widely used immunosuppressive drug with a high affinity for erythrocytes. It was hypothesized that the hydrophobic agent would interact with the erythrocyte membrane, which could cause a shape change and alter cell deformability. Administration of 300 mg cyclosporine in vivo and incubation of erythrocytes with concentrations up to 100 mg l-1 in vitro at room temperature showed that cyclosporine is found in the cytoplasm, but not in the membrane of erythrocytes and that cell shape or deformability were not affected. Incubation of erythrocytes with the highest cyclosporine concentration (100 mg l-1) at 37 degrees C lead to a time-dependent, slight stomatocytic shape transformation, indicating that the drug is intercalated preferentially into the inner hemileaflet of the membrane under these conditions. Cyclosporine metabolites had no effect on the cell shape. The shape of erythrocyte ghosts was neither affected by cyclosporine nor by its metabolites. It is concluded that cyclosporine is bound in the erythrocyte cytoplasm and does not affect the cell membrane and cell deformability at therapeutic concentrations. These results may contribute to a better understanding of the interactions of cyclosporine with cells. PMID- 8477793 TI - Cerebral trauma and alcohol abuse. AB - We report results of clinical examinations, computed tomography, quantitative electroencephalography (QEEG), and cerebral blood flow measurements performed on a series of 56 consecutive brain injury patients including 15 alcohol abusers and 41 non-alcoholic subjects. Greater volumes of intracranial haemorrhage were noted in the alcoholics for a similar severity of injury and local brain atrophy became more pronounced in them during a follow-up of 1 year. After this time, the third ventricle width, distance between frontal horns, the sum of lateral ventricle dimensions and cortical sulci were all markedly larger in the alcoholics. The QEEG results also indicated a weaker improvement in the alcoholics. The cerebral blood flow at the site of the injury was initially slow in the alcoholics when compared to the contralateral region of the other hemisphere, although these differences disappeared during the follow-up. Permanent occupational disability was also found to be associated with pretraumatic alcohol abuse. The findings indicate that ethanol abuse is not only commonly associated with cerebral trauma but is also a risk factor for a more severe brain damage following the injury. PMID- 8477794 TI - Alternative splicing of human G6PD messenger RNA in K562 cells but not in cultured erythroblasts. AB - The biochemical properties of glucose-6-phosphate dehydrogenase (G6PD) vary in different tissues, and different protein isoforms of the enzyme have been described. Alternative splicing of G6PD intron VII has been detected in transformed lymphoblasts, granulocytes and spermatocytes; the function of this mRNA species is still unknown. We developed a PCR for detecting alternatively spliced G6PD mRNA in K562 and in erythroblasts at different stage of maturation obtained from human peripheral BFU-E in order to evaluate a possible physiological role during erythroid maturation. Trace events of alternative splicing of G6PD intron VII sequences were observed in K562 cells but not in BFU E-derived erythroid precursors; we consider this phenomenon a non-functional activity in the cells analysed. PMID- 8477795 TI - Effect of ageing on postprandial conjugated and unconjugated serum bile acid levels in healthy subjects. AB - Colorectal cancer is a disease of elderly subjects. A decreased ileal absorption of bile acids in elderly subjects may lead to an increased exposure of the colonic mucosa to secondary bile acids. This may contribute to an enhanced risk of colorectal cancer. In this study fasting and postprandial conjugated and unconjugated serum levels of cholic, chenodeoxycholic, and deoxycholic acid in 12 elderly and 12 younger subjects were investigated. Intestinal transit time, gallbladder emptying and jejunal bacterial flora were also studied in both age groups. Fasting levels of conjugated and unconjugated serum bile acids were similar in both age groups. Postprandial levels of all individual conjugated bile acids increased to a significantly higher extent in the younger subjects. Postprandial unconjugated serum bile acid levels did not differ significantly between both age groups, although unconjugated deoxycholic levels tended to increase to higher levels in the elderly. Results of jejunal bacterial counts, gallbladder emptying and intestinal transit time were similar in both groups. These data suggest that conjugated bile acids are reabsorbed less effectively in elderly subjects. PMID- 8477796 TI - Molecular cloning of porcine T cell receptor alpha, beta, gamma and delta chains using polymerase chain reaction fragments of the constant regions. AB - Fragments of the constant regions of porcine alpha, beta, delta and two types of gamma T cell receptor (TcR) chains were obtained by reverse transcription and polymerase chain reaction (PCR). Screening of a porcine peripheral T cell cDNA library with these PCR fragments led to the isolation of porcine TcR alpha, beta, gamma and delta chain clones. Sequence analysis of these clones and the respective PCR fragments demonstrated the existence of one alpha, one beta, three gamma and one delta chain isotype. Comparisons of the deduced amino acid sequences of the constant region with other species revealed a significant homology. For two of the three identified porcine gamma chain insertions of 38 and 40 amino acids were found within the hinge region. In addition, our sequence data demonstrate a high variability in the cytoplasmic C gamma domain among the three porcine TcR gamma isotypes as well as between species, which might be of structural and/or functional significance. Comparison with biochemical data indicate the existence of four porcine TcR gamma isotypes. PMID- 8477797 TI - The fate of human peripheral blood lymphocytes after transplantation into SCID mice. AB - Human peripheral blood lymphocytes (hu-PBL) can be adoptively transferred by intraperitoneal injection into mice with severe combined immunodeficiency (SCID). The transplanted lymphocytes can produce immunoglobulin (Ig), respond to antigens, and survive for months in this chimeric model (hu-PBL SCID). However, whether the lymphocytes actually repopulate and reconstitute lymphoid structures and organs has been subject of some debate. To address this question and to characterize the hu-PBL SCID model better, we employed a novel technique for the identification of human cells in xenogeneic mice. We used fluorescence in situ hybridization (FISH) with a biotinylated DNA probe to all human centromeres. We demonstrated that FISH could be used to detect human cells when they accounted for less than 1% of human/mouse cell mixtures; it could also be employed for the identification and localization of individual human cells in tissue sections. By using FISH, we studied 31 SCID mice injected with 1.5 x 10(7)-4 x 10(7) hu-PBL via intravenous (i.v.) or intraperitoneal (i.p.) routes. In the 6 i.v.-injected mice, we found that the human cells were removed from the circulation into the lung within 1 h. In 22 of 25 i.p.-injected animals, 90-3716 micrograms/ml of human IgG was found in the sera at 3 to 13 weeks after transplantation (a.t.). Human cells colonized the peritoneal cavity and persisted for up to 13 weeks a.t. and, in the 12 mice studied, accounted for 4% to 57% of the cells in the peritoneal fluid. However, only rare, isolated human cells were found in the spleen, blood, bone marrow, lung or Peyer's patches. In 7 of 19 mice that received hu-PBL i.p. from Epstein-Barr virus-seropositive donors, we found masses of human cells usually beneath the peritoneal lining but sometimes infiltrating normal tissue. We conclude that FISH offers a simple means for accurate identification of human cells in the xenogeneic mouse. Although there is colonization of the peritoneal cavity in most mice, and development of lymphoid masses in some, there is no reconstitution of lymphoid structures and only minimal engraftment of lymphoid organs by human cells in conventionally-prepared hu-PBL SCID constructs. PMID- 8477798 TI - Early appearance and activation of natural killer cells in tumor-infiltrating lymphoid cells during tumor development. AB - We investigated NK cell infiltration into tumor developing lesions at early stage of tumor development after intraperitoneal inoculation of 3LL lung carcinoma into syngeneic C57BL/6 mice. Natural killer (NK) cells, which were detected by anti-NK 1.1 monoclonal antibody (mAb), remarkably increased in number in tumor-developing lesions (peritoneal cavity) as early as day 3 after inoculation of 3LL. The tumor infiltrating NK cells from 3LL-inoculated mice produced a high level of interferon-gamma by co-culture with 3LL and showed enhanced cytotoxic activities against both NK-sensitive (YAC-1) and NK-resistant (3LL and P815) tumors. Furthermore, mice depleted of NK cells by injection of anti-NK 1.1 mAb or anti asialo GM1 antibody showed shorter survival times after intraperitoneal inoculation of 3LL when compared with control mice. These results suggest that NK cells infiltrate the tumor-developing lesion at an early stage and may participate in the early protection against tumors through production of a high amount of interferon-gamma and enhanced cytotoxicity at tumor-bearing sites. PMID- 8477799 TI - Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing of Candida albicans. AB - Mouse peritoneal and splenic macrophages treated with interferon-gamma (IFN gamma) and infected with the yeast Candida albicans expressed high fungicidal activity in vitro that correlated with increased nitrite concentrations in culture supernatants. Both effects were reduced by an inhibitor of nitric oxide (NO) synthesis which, in vivo, impaired the animals' ability to mount a footpad reaction and clear the fungus from infected organs. Because T helper type-2 (Th2) cytokines in candidiasis are known to limit the expression of protective Th1 functions, we tested the effect of interleukin (IL)-4 and IL-10 on candidacidal activity and NO production of IFN-gamma-activated macrophages. Fungal killing and NO secretion were inhibited, in a dose-dependent manner, by the two cytokines either separately or in combination. Impaired candidacidal activity was also demonstrable in the presence of monoiodoacetic acid, an inhibitor of phagocytosis. These data demonstrate that NO is involved in macrophage killing of C. albicans and support the notion that regulation of Th1 effector function by IL 4 and IL-10 might involve modulation of NO synthesis. PMID- 8477800 TI - Regulation of CD69 expression on human natural killer cells: differential involvement of protein kinase C and protein tyrosine kinases. AB - Human peripheral blood natural killer (NK) cells (CD56+, CD16+, CD3 epsilon- lymphocytes) express CD69 after their stimulation by interleukin-2 (IL-2) or interferon-alpha (IFN-alpha). This activation antigen represents a triggering surface molecule in NK cell clones as its stimulation triggers the cytolytic machinery of these cells. However, the mechanisms regulating the expression of CD69 in NK cells are unknown despite the functional relevance of CD69 in NK cell activation. Thus, we have analyzed the role of protein kinase C (PKC) and protein tyrosine kinases (PTK) in the expression of CD69 on purified NK cells activated by IL-2, IFN-alpha, anti Fc gamma RIII (CD16) monoclonal antibodies or by K562 target cells. We found that CD69 is induced on NK cells not only by IL-2 and IFN alpha but also by activation of the CD16 pathway, the interaction with NK target cells and the direct activation of PKC by phorbol 12-myristate 13-acetate (PMA), indicating that CD69 induction is associated to different NK activation pathways. The treatment with the PKC inhibitor staurosporine abolished the induction of CD69 induced by PMA or K562. However, it did not significantly affect CD69 induction by IL-2, IFN-alpha or CD16 cross-linking. This demonstrates that whereas PKC can play a central role in the regulation of CD69 expression in some instances (response to K562 cells or PMA), it does not participate in others (response to IL-2, IFN-alpha or anti CD16 monoclonal antibodies). On the other hand genistein, a competitive inhibitor of PTK enzymes, blocked the expression of CD69 induced by activation of NK cells via IL-2 or IFN-alpha receptors, CD16 and K562 receptor(s), indicating that stimulation of PTK is a common step in the signal transduction events leading to the induction of CD69 antigens after the activation of NK cells via these receptors. PMID- 8477801 TI - Linkage disequilibrium between TAP2 variants and HLA class II alleles; no primary association between TAP2 variants and insulin-dependent diabetes mellitus. AB - The TAP1 and TAP2 genes, located in the HLA class II region, encode subunits of a peptide transporter. Both genes display limited genetic variability; four different nucleotide substitutions have been found in the TAP2 gene. Here studies on linkage disequilibrium between TAP2 variants and HLA class II alleles are reported, in an attempt to evaluate whether TAP2 variants are associated with insulin-dependent diabetes mellitus (IDDM). As reported previously, a significant decrease of homozygosity for TAP2 alleles encoding alanine at residue 665 (665 Ala) and glutamine at 687 (687 Gln) paralleled by an increase in homozygosity for TAP2 alleles encoding threonine at residue 665 (665 Thr) and a stop codon at 687 (687 Stop), was found in both Finnish and Norwegian IDDM patients compared to random controls. However, a strong linkage disequilibrium between these TAP2 polymorphisms and given HLA-DR and -DQ genes was observed among healthy controls. The frequent 665 Thr and 687 Stop variants were in linkage disequilibrium both with the DR4-DQ8 and the DR3-DQ2 haplotypes, haplotypes which are strongly associated with IDDM. In contrast, the DR1-DQ5 and DR13-DQ6 (e.g. DQB1*0603) haplotypes, which are decreased among IDDM patients, were associated with the 665 Ala and 687 Gln variants. Thus, when DR- and DQ-matched patients and controls were compared, associations of the investigated TAP2 variants and IDDM were no longer detectable. These data, therefore, indicate that the associations previously found between certain TAP2 variants and IDDM are secondary to a primary association between this disease and particular DQ alpha beta heterodimers. PMID- 8477802 TI - Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. AB - The characteristics of soluble interleukin-6 receptor (sIL-6R) in murine sera were examined. To investigate a relationship between serum sIL-6R level and autoimmune diseases, quantitative analysis of serum sIL-6R in MRL/lpr mice was performed by an enzyme-linked immunosorbent assay. The serum sIL-6R level in MRL/lpr mice of both sexes was below the detection limit (< 1.0 ng/ml) at 8 weeks of age, but it increased in accordance with age and reached 42 +/- 9.3 ng/ml in female and 31 +/- 13 ng/ml in male mice at 30 weeks of age. In MRL/+ mice, although an age-associated increase in serum sIL-6R level was observed, it was much less extensive than that in MRL/lpr mice. Elevated serum sIL-6R level at the age of 30 weeks was observed in female and male (NZB x NZW)F1 mice (32 +/- 10 ng/ml and 17 +/- 5.0 ng/ml, respectively), and male BXSB/Mpj Yaa mice (42 +/- 18 ng/ml), suggesting that elevated serum sIL-6R in aged mice is one of the characteristics of autoimmune-prone mice. Quantitative analysis of serum IL-6 in MRL/lpr revealed that the serum sIL-6R level correlated well with the serum IL-6 level. We also showed that sIL-6R in the sera from MRL/lpr mice could mediate the IL-6 functions through the IL-6 signal-transducing receptor component gp130, suggesting that elevated production of sIL-6R may partly contribute to development of autoimmune disease in MRL/lpr mice. PMID- 8477803 TI - The structure of the mu/pseudo light chain complex on human pre-B cells is consistent with a function in signal transduction. AB - Prior to immunoglobulin (Ig) light (L) chain rearrangement, pre-B cells can express mu heavy (H) chains at the cell surface in association with pseudo (psi) L chains. This complex may be essential for B cell development. We have investigated the composition of the mu/psi L chain complex of a human pre-B cell line, in view of its potential role in transmembrane signal transduction. The mu/lambda receptor of a mature B cell line was analyzed in comparison. The mu/psi L chain complex is associated with disulfide-linked molecules that are homologous or identical to the mb-1 and B29 proteins, known to be integral components of membrane Ig receptors on mature B cells. Both receptors contain tyrosine (Tyr) kinase activity. In the mu/lambda receptor, the lyn and lck Tyr kinases could clearly be identified. The mb-1 and B29 proteins in both mu/lambda and mu/psi L chain receptors are substrates for in vitro phosphorylation on Tyr, but also on serine (Ser) and threonine (Thr) residues. The undefined mu-associated Ser/Thr kinase also phosphorylates the src-related kinases in the mu/lambda receptor and a 43-kDa mu-associated protein that is present in both complexes. The 43-kDa protein may be an integral part of both receptor types, or a transiently associated molecule instrumental in the signaling process. We conclude that the mu/psi L receptor on human pre-B cells fulfills the presently known criteria to function as a signal transduction unit. PMID- 8477804 TI - Structural motifs involved in human IgG antibody effector functions. AB - A humanized IgG antibody to CAMPATH-1 antigen (CDw52) is known to be lympholytic both in vitro and in vivo. So as to improve therapeutic potency through protein engineering strategies, we wish to define the structural motifs underlying some of the documented differences in function between human (h) IgG1 and IgG4 forms of the antibody. By the creation of heavy chain domain-switch and intra-domain recombinant antibodies we have established an important role for the carboxy terminal half of the CH2 domain in determining differential behaviour in antibody dependent cytotoxicity (ADCC) and in complement lysis. If this same region were necessary for the effector mechanisms that operate in vivo, then it might be possible to improve antibody effector functions by construction of novel antibodies that possess within the one molecule multiple copies of the crucial hinge-CH2 associated structures. Although our previous work suggested that the hIgG4 CAMPATH-1 antibody was ineffective at ADCC, we found this to be so only in some individuals. In others, IgG4, and indeed all the IgG subclasses were able to mediate ADCC. Overall, though, hIgG1 remains the best choice isotype for lytic therapy in vivo. PMID- 8477805 TI - Activation of uterine intraepithelial gamma delta T cell receptor-positive lymphocytes during pregnancy. AB - Intraepithelial lymphocytes (IEL) of the uterus of non-pregnant sheep were analyzed by single- and two-color flow cytometry. Very few lymphocytes carrying classical B and T cell markers (CD5, surface immunoglobulin) were detected in the uterine epithelial cell suspensions and all IEL expressed the CD8 surface marker although with varying intensities. Three distinct subpopulations were identified including a major (46-56%) population of CD8+CD45R- gamma delta T cell receptor (TcR)-negative cells and approximately equal numbers of CD8+CD45R+ gamma delta TcR- and CD8+CD45R+ gamma delta TcR+ lymphocytes. The same three subpopulations were also present in the interplacentomal areas of the uterus of ewes at a late stage of pregnancy but there was a dramatic increase (60-70%) in the gamma delta TcR+ subpopulation. In addition, a pronounced increase in both size and granularity was observed in the IEL population of pregnant uteri and this was attributed to the gamma delta TcR+ cells. Light and electron microscopic examination of these gamma delta TcR+ IEL revealed an increase in metabolic activity and the formation of exceptionally large cytoplasmic granules and confirmed their restricted localization within the uterine epithelium close to the trophoblast. These results represent for the first time, a clear example of the activation of gamma delta TcR+ cells which is not associated with an ongoing disease process or infection. gamma delta TcR+ cells have recently been observed in the epithelium of the murine reproductive tract and were characterized by their unique homogeneous receptor structure. The present results indicate that these cells may play an important physiological role during pregnancy. PMID- 8477806 TI - Real-time measurement of antigenic peptide binding to empty and preloaded single chain major histocompatibility complex class I molecules. AB - Cytotoxic T lymphocytes (CTL) recognize peptides in association with major histocompatibility complex (MHC) class I proteins, but how peptides bind to class I is not well understood. We used a fluorescence technique to measure antigenic peptide binding to a soluble, single-chain Kd (SC-Kd) molecule in which the Kd heavy chain was connected by a 15-residue link to beta 2-microglobulin. Peptides were covalently labeled at their N terminus with dansyl, and binding of dansylated Kd-restricted peptides to SC-Kd resulted in significant fluorescence enhancement, which could be inhibited by unmodified Kd-restricted peptides. Real time binding of a dansylated peptide could be followed by monitoring the fluorescence at 530 nm. The dansylated Plasmodium berghei circumsporozoite (PbCS) 263-260 peptide bound to "empty" SC-Kd with an association rate constant of 1140 M-1s-1, and the subsequent spontaneous dissociation of the SC-Kd-peptide complex was slow. The dissociation increased dramatically after addition of excess unlabeled PbCS 253-260 peptide, but with a slower association constant for unlabeled peptide, 77 M-1s-1. Thus, the Kd-peptide complex on the surface of antigen-presenting cells should be stable, but high concentrations of peptides in the endoplasmic reticulum (ER) lumen would allow for peptide exchange on Kd before export to the surface. The apparent activation energy for PbCS 253-260 peptide binding to SC-Kd was 6.78 +/- 0.64 kcal/mole, similar to values previously reported for antigen-antibody interactions. PMID- 8477807 TI - Interleukin-9 stimulates in vitro growth of mouse thymic lymphomas. AB - The ability of interleukin (IL)-9 to stimulate the in vitro proliferation of freshly collected mouse thymic lymphoma cells was tested on a panel of 45 tumors, induced by N-methyl-N-nitrosourea (MNU) or by X-ray irradiation. IL-9 significantly stimulated the proliferation of 26 of these tumors. Out of 11 other factors tested, only IL-2, IL-4 and IL-7 showed similar activities. In addition to the responses to IL-9 alone, a potent synergy was often observed between IL-9 and IL-2 for MNU-induced tumors. Synergies between IL-9 and IL-7 or IL-9 and IL-4 were also observed but less frequently. The growth-promoting activity of IL-9 and the synergistic activities of IL-2 and IL-9 for thymic lymphoma cells were confirmed with cell lines established from the fresh tumors. PMID- 8477808 TI - Chicken major histocompatibility complex class II B genes: analysis of interallelic and interlocus sequence variance. AB - Five different chicken B-LB genes were cloned and sequenced. The comparison of these sequences shows that they can be classified as members of two different families, the B-LBII family (containing the B-LBI and B-LBII genes) and the B LBIII family (containing the B-LBIII, B-LBIV, and B-LBV genes). The extent of polymorphism within each of these families was assessed by in vitro amplification of DNA fragments encompassing exon 2 in several haplotypes. The nucleotide sequences were determined, and pairwise relationships were evaluated. In the course of this work, a sixth gene termed B-LBVI was identified, defining a third family (B-LBVI family). Polymorphism of the B-LBIII or B-LBVI families is far less extensive than that of the B-LBII family. In this latter, the distribution of conserved and polymorphic residues is similar to what has been described in mammals. These families seem to have been generated by gene duplication events giving rise to several isotypes, as observed in mammals. However, phylogenetic analyses indicate that these families are not homologous to their mammalian counterparts. Evaluation of the level of transcription of these different genes showed that genes from the B-LBII family are predominantly transcribed over those of the other families. PMID- 8477809 TI - Characterization of the human T cell receptor alpha-chain repertoire and demonstration of a genetic influence on V alpha usage. AB - Despite considerable knowledge of the determinants and profile of the T cell receptor (TCR) beta-chain repertoire, very little is known about the repertoire of the V alpha and J alpha segments of the TCR in man or mouse. We have used the anchored polymerase chain reaction (PCR) to analyze the human TCR alpha-chain repertoire at the mRNA level in peripheral blood lymphocytes. We find marked differences in the usage of individual V alpha segments. The V alpha repertoire is determined both by differences in the use of individual V alpha gene segments at the time of gene rearrangement and by genetic influences on the selection of the expressed V alpha repertoire, presumably during thymic maturation. Analysis of the J alpha repertoire shows non-random usage of individual J alpha segments but no obvious relationship to chromosomal position. We also report three new V alpha segments, three new J alpha segments and possible allelic variation in V alpha gene segments. Two unusual TCR alpha transcripts are described which add new information on the nature of TCR alpha transcript assembly. PMID- 8477810 TI - Essential role of tumor necrosis factor-alpha in the differentiation of human tonsil in vivo induced B cells capable of spontaneous and high-rate immunoglobulin secretion. AB - Human tonsils contain B cells capable of spontaneous and high-rate immunoglobulin (Ig) secretion in vitro. These cells are in vivo induced mature B cells, and, as such, they provide and adequate model for studying tonsil B cell differentiation. The present report analyzes the effect of a variety of factors on purified tonsil B cells capable of spontaneous IgG secretion in fetal calf serum (FCS)-containing and serum-free supplemented cultures. Tumor necrosis factor-(TNF) alpha was found to be important for these B cells to reach the high-rate IgG-secreting stage, as is indicated by the following findings: (a) none of the factors used modified tonsil B cell IgG secretion in FCS-containing cultures; (b) TNF-alpha (5-20 ng/ml), but not other cytokines or factors including interleukin (IL)-6, was capable of restoring missing IgG production in serum-free supplemented cultures of tonsil B cells; and (c) IgG secretion in FCS-containing cultures was inhibited by the addition of blocking anti-TNF-alpha antibodies, but not anti-IL-6 antibodies, and this inhibition could be specifically reversed by exogenous TNF alpha. TNF-alpha was actively produced by tonsil B cells (range 120-750 pg/ml) in the presence, but not in the absence, of FCS. The TNF-alpha inductive effect occurred during the first 12 h of culture and did not require DNA synthesis. These results indicate that the early and endogenous generation of TNF-alpha seems to be essential for tonsil in vivo induced B cells to differentiate into the high-rate Ig-secreting stage. PMID- 8477811 TI - An intermolecular mechanism of T cell help for the production of antibodies to the bacterial pathogen, Chlamydia trachomatis. AB - Antibodies that neutralize infectivity are directed at the antigenically variant major outer membrane protein (MOMP) of Chlamydia trachomatis. A vaccine for chlamydia will need to include T cell determinants that elicit T helper (Th) cells which provide help to MOMP-specific B cells. A limited number of determinants on MOMP are able to elicit Th cells and sequence diversity in the MOMP molecule may alter T cell recognition of these determinants. We investigated whether two sequence invariant proteins of C. trachomatis that are both abundant and immunogenic could elicit T cell help for the production of antibody to MOMP. We found that outer membrane protein 2 (OMP2) but not outer membrane protein 3 (OMP3) was able to prime BALB/c mice for an anamnestic anti-MOMP response following boost with the intact organism. This demonstration of an intermolecular mechanism of T cell help in a bacterial system has important implications for the development of a chlamydial vaccine as well as the design of vaccines for other antigenically variant non-viral pathogens. PMID- 8477812 TI - Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection. AB - A phenotypical analysis carried out by indirect immunofluorescence and two-color cytofluorometry showed that the number of lymphocytes bearing the gamma delta T cell receptor (TcR) heterodimer was dramatically increased in the blood of six children with Brucella melitensis infection. Most in vivo expanded gamma delta T cells reacted with a monoclonal antibody which identifies V delta 2 gene products and a significant proportion expressed CD25 and HLA-DR activation antigens. In addition, whereas only a few gamma delta T lymphocytes were CD8+, nearly all were CD4-. Highly enriched populations of both alpha beta and gamma delta T cells were obtained by negative immunoselection from three subjects with brucellosis sampled during convalescence. Despite the different form of their TcR, the proliferation of these two major T cell subsets in response to a mitogenic anti-CD3 monoclonal reagent (OKT3) was optimal. In contrast, alpha beta, but not gamma delta, T lymphocytes proliferated vigorously in response to the antigenic stimulus elicited by heat-killed Brucella. Further studies are, therefore, needed to determine whether the selective expansion of the gamma delta T cell subpopulation observed during the clinical course of the infection is driven by antigenic determinant(s) borne by the pathogen in vivo or is due to host-derived stimuli, such as autologous heat-shock proteins expressed on the surface of the infected cells. PMID- 8477813 TI - The level of N-region diversity in T cell receptors is not pre-ordained in the stem cell. AB - The alpha beta T cell repertoires of adults and neonates are distinctly different. For example, T cell receptors (TcR) from adult animals have substantial N-nucleotide addition at their V-D-J junctions while those from neonatal animals do not. This dichotomy reflects a rather abrupt change in expression of the terminal deoxynucleotidyl transferase (TdT) gene in thymocytes on day 4 after birth. We have asked whether this change is due to the differentiation of successive waves of stem cells harboring different potentials for TdT expression, a scenario like the one proposed to explain developmental regulation of gamma delta T cell repertoires. Reconstitution of adult severe combined immunodeficiency mice with either fetal liver or adult bone marrow precursors gave rise to T cells with substantial N-region diversity in their TcR, even at the earliest points of reconstitution. It is most likely, then, that the abrupt change in TdT gene expression in day 4 thymocytes is due to an environmentally induced switch-on. PMID- 8477814 TI - Clonal deletion as direct consequence of an in vivo T cell response to bacterial superantigen. AB - To date clonal deletion of peripheral mature T cells is restricted to in vivo model systems characterized by prolonged exposure of mice to antigens and clonal T cell expansion preceding clonal deletion. Here we describe that upon challenge of mice with the superantigen staphylococcal enterotoxin B two immediate events become imposed on ligand-reactive V beta 8+ T cells in lymph node cells draining the local site of injection. First, and within hours V beta selective clonal deletion is initiated via an apoptotic process. Second, the remaining V beta 8+ T cells first develop a profound state of ligand-specific unresponsiveness and subsequently initiate clonal in vivo growth. It is suggested that the dichotomy of events observed reflects a direct consequence of T cell receptor occupancy in the context of inappropriate signalling. PMID- 8477815 TI - Quantitative analysis of molecules which distinguish functional compartments within germinal centers. AB - Five zones in the secondary follicles of human tonsils are described, which are distinguished by the phenotype of their constituent cells. Moving from the apex to the base of the follicle the zones are termed: follicular mantle, outer zone, apical light zone, basal light zone and dark zone. The dark zone contains proliferating, CD77high, centroblasts and thin, widely spaced processes of follicular dendritic cells (FDC). The apical and basal light zones on the other hand contain a dense network of FDC which express CD21 and CD54 strongly. The FDC of the apical light zone differ from those of the basal light zone by their high expression of CD23. Centroblasts of the dark zone give rise to non-proliferating centrocytes which move apically through the light zone (Eur. J. Immunol. 1991. 21:2951). The centrocytes of the basal light zone are more pyroninophilic, more closely-packed and larger than those in the apical light zone. Consequently, by conventional histology the basal light zone appears to be part of the dark zone. The nomenclature adopted, however, adheres to the convention that the dark zone is filled with proliferating centroblasts. Cells undergoing apoptosis were identified both in the dark and light zones, but more than half of these cells were located in the basal light zone. This is consistent with the concept that the progeny of cells which undergo somatic mutation in their immunoglobulin variable region genes in the dark zone migrate to the light zone where they are selected on the basis of their capacity to bind to antigen held on FDC. Cells receiving an antigen-dependent signal survive while those that do not kill themselves by apoptosis. The outer zone does not contain CD23high cells and in this way is distinguished from the adjacent follicular mantle and apical light zone. It contains small lymphoid cells, blasts and plasmacytoid cells. Many cells of the outer zone express CDw75 strongly. The outer zone also extends as a narrow band around the dark zone. Possible roles of FDC and T cells of the light zone and outer zone in inducing centrocytes to differentiate to memory cells or plasmablasts are discussed. PMID- 8477816 TI - Protein kinase C inhibitors potentiate angiotensin II-induced phosphoinositide hydrolysis and intracellular Ca2+ mobilization in renal mesangial cells. AB - Stimulation of mesangial cells with angiotensin II leads to rapid phosphoinositide hydrolysis and subsequent mobilization of intracellular Ca2+. Previous studies indicated that activation of protein kinase C (PKC) triggers a negative-feedback signal, which limits phosphoinositide turnover. By comparing the relative susceptibility of PKC isoenzymes to phorbol ester-induced down regulation with the down-regulation of the functional cell response, i.e. feedback inhibition of inositol trisphosphate production, we inferred that PKC alpha and PKC-delta are candidates for regulating phosphoinositide hydrolysis in mesangial cells. To test this hypothesis further, we examined the effects of inhibitors of PKC, that are reportedly not active on PKC-delta, on angiotensin II stimulated phosphoinositide degradation and Ca2+ mobilization. Pretreatment of mesangial cells with the PKC inhibitors staurosporine and K252a potently augmented inositol trisphosphate and 1,2-diacylglycerol formation as well as Ca2+ mobilization in response to angiotensin II. These results suggest that PKC-alpha, but not PKC-delta, is the most likely candidate mediating feedback inhibition of angiotensin II-stimulated phosphoinositide turnover in mesangial cells. PMID- 8477817 TI - Endothelin receptors stimulate both phospholipase C and phospholipase D activities in different cell lines. AB - Endothelin (ET) receptor-binding assays using [125I]ET-1 in C6-glioma cells and in Rat-1 and Swiss 3T3 fibroblasts indicated the presence of two binding sites, one of which binds agonists at the pM range and the other at the nM range. All three cell lines exhibited the same pharmacological profile for agonist binding (ET-1 congruent to sarafotoxin-b > ET-3), which suggests that the receptor is of the ETA type. Binding of ET-1 to the receptor resulted in activation of two phospholipases, phospholipase C (PLC) and phospholipase D (PLD). The activation of PLC or PLD by endothelin in the three cell lines was mediated by the high affinity binding site (nM range) and was not significantly affected by either extracellular or intracellular Ca2+. Measurement of PLD activation by ET-1 and/or phorbol 12-myristate 13-acetate (PMA), in the presence and absence of two potent inhibitors of protein kinase C (PKC), strongly suggests that activation of PLD by ET receptor in C6 glioma cells as well as in Rat-1 and Swiss 3T3 fibroblasts involves both PKC-dependent and PKC-independent mechanisms. PMID- 8477818 TI - Angiotensin AT1 receptors mediate a positive inotropic effect of angiotensin II in guinea pig atria. AB - Angiotensin II receptors in adult guinea pig hearts were characterized using [125I][Sar1,Ile8]angiotensin II and the non-peptidic receptor antagonists, losartan and PD 123319. Autoradiographic experiments and binding experiments performed on membrane preparations showed that cardiac tissues mainly expressed losartan (Kd = 30 nM)-sensitive AT1 receptors. In contraction experiments, angiotensin II produced a positive inotropic effect in both right and left atrial preparations. This action was prevented by losartan but not by PD 123319. It is concluded that mainly AT1 receptors are expressed in guinea pig atria and that these sites are responsible for the positive inotropic effect of angiotensin II. PMID- 8477819 TI - Recent advances in the molecular biology of growth-hormone secreting human pituitary tumours. AB - The application of DNA technology has led to significant progress in our understanding of the aetiology of GH-secreting pituitary tumours. X-chromosome inactivation and RFLP analysis has revealed that GH-secreting tumours are monoclonal in origin and thus arise as a consequence of a somatic mutation within a single cell. Using PCR and sequence analysis, such a mutation has been identified in 30-40% of tumours. This is the so-called gsp mutation in which the gene for the alpha s subunit of the Gs protein is converted to an oncogene the expression of which results in constitutive adenyl cyclase activity and thus excessive cAMP production. In our own studies, we demonstrate that it is unlikely that a defect within the promoter region of the GH gene will prove to be a cause of excessive GH secretion in acromegaly. In contrast, we have shown that the GH gene is hypomethylated in tumour derived DNA and this may account, at least in part, for abnormal GH gene expression. PMID- 8477820 TI - Molecular biology of insulin resistance. AB - Insulin resistance is an essential feature of a great variety of clinical disorders, like diabetes mellitus, obesity, essential hypertension, and is primarily due to a defect in hormone action at the cellular level. In the past decade application of novel research techniques including recombinant DNA technology have paved the way to understand the mechanisms of insulin action and its alterations at the molecular level. The first step in insulin action is the activation of the insulin receptor. The insulin receptor is a tetrameric protein consisting of two extracellular alpha- and two transmembrane beta-subunits. Binding of insulin to the alpha-subunit causes autophosphorylation of the intracellular beta-subunit region on tyrosine residues thereby activating the receptor. How the hormonal signal is subsequently transduced within the cell is still quiet unclear. The activated insulin receptor appears to couple to cytosolic receptor substrates which can affect different signaling cascades eliciting the pleiotropic hormone response on cell metabolism and growth. Most proteins involved in the signal transduction pathway of insulin are not known yet, but each of them might play a role in the various forms of insulin resistance. Taking the insulin receptor as an exemplary protein involved in insulin action we review molecular mechanisms regulating insulin receptor activity, gene expression, and the role of natural occurring insulin receptor gene mutations in patients with insulin resistant diabetes mellitus. It is outlined how the combination of both clinical medicine and molecular biology not only helps to understand insulin action and the pathogenesis of insulin resistance, but also leads to new avenues in the differential diagnosis, therapy, and possibly prevention of this heterogenous but most frequent metabolic and endocrine disorder. PMID- 8477821 TI - Familial glucocorticoid resistance: an overview. PMID- 8477822 TI - Transcriptional control of pancreatic islet hormones gene expression. AB - Initiation of transcription requires transcription factors that recognize specific DNA sequences present in promoters and enhancers of the respective genes. Cell-specific expression of the pancreatic islet hormone genes is conferred by a cell-specific combination of transcription factors. The DNA binding sites and cDNAs of some of them have been characterized. An islet specific enhancer-binding protein of the rat glucagon gene recognizes also cis acting elements of the rat insulin I and rat somatostatin genes. Thus identical or related factors may be involved in the expression of these pancreatic genes, reflecting that the different islet cell types arise from a common progenitor cell. The characterization of islet-specific transcription factors may lead to regulatory genes whose products specify islet cell phenotypes during development. Basal transcriptional activity of islet hormone genes can be enhanced by metabolic, humoral or nerve signals via various second messenger systems. Cyclic AMP acts through distinct response elements. The islet cells are electrically excitable and known secretagogues increase electrical activity and elevate cytosolic calcium concentration. Depolarization-induced activation of voltage dependent calcium channels stimulates rat glucagon gene transcription suggesting that calcium is an intracellular signal for pancreatic islet hormone gene transcription. PMID- 8477823 TI - Genetic screening for multiple endocrine neoplasia type 2. PMID- 8477824 TI - Perspectives in gene therapy with recombinant adenoviruses. PMID- 8477825 TI - Synaptic density of axotomized hypoglossal motorneurons following pharmacological blockade of the microglial cell proliferation. AB - The purpose of the present study was to examine the possible role of reactive microglia in the removal of presynaptic terminals following motor axon injury. Quantitative electron microscopy was used to examine synaptic numbers and total relative synaptic coverage on hypoglossal neuronal perikarya following hypoglossal nerve transection in the rat with or without pharmacological blockade of the axotomy-induced microglial cell proliferation. In a previous study we have shown that the axotomy-induced microglial cell proliferation is selectively inhibited by continuous infusion of cytosine-arabinoside (ARA-C) into the ventricular system of the adult rat brain. Adopting this procedure in the present study resulted in an almost complete elimination of reactive microglia. There was a statistically significant decrease in the number of synapses and the relative synaptic coverage in untreated as well as ARA-C-treated animals 4 and 7 days after nerve transection. Immunocytochemical labeling of terminals in the hypoglossal nucleus using antibodies to synaptophysin showed a reduction in immunoreactivity around hypoglossal nerve cell bodies ipsilateral to nerve transection in both groups of animals. These results indicate that reactive microglia are not responsible for detachment of presynaptic terminals following motor axon injury. PMID- 8477826 TI - The role of the septohippocampal pathway in the regulation of hippocampal field activity and behavior: analysis by the intraseptal microinfusion of carbachol, atropine, and procaine. AB - The role of the septohippocampal pathway in the regulation of hippocampal field activity and behavior was assessed using the technique of intraseptal microinfusion of carbachol, atropine, and procaine. The effects of these manipulations were assessed by comparing them with the effects of intraseptal saline control infusions on spontaneously occurring motor behaviors and their correlated hippocampal field activities. In control conditions hippocampal theta field activity, with up to 40% of the total power concentrated in a 1-Hz band around the peak frequency, was recorded only during type 1 voluntary motor behaviors. Hippocampal large-amplitude irregular activity was recorded during type 2 automatic motor behaviors and during immobility. Microinfusion of carbachol into the MS/vDBB (medial septum/vertical limb of the diagonal band of Broca) resulted in continuous theta field activity regardless of what type of motor behavior the animal performed or whether it was immobile. However, under these conditions the performance of a voluntary movement consistently resulted in an upward shift of theta frequency, demonstrating that the frequency of carbachol elicited type 2 theta can be modulated by the behavioral activation of type 1 theta. The subsequent infusion of atropine abolished the carbachol-elicited theta, while that occurring during type 1 voluntary movement was preserved. In contrast to the selective blockade of carbachol-elicited theta by atropine, procaine suppression of the MS/vDBB abolished both spontaneous movement-related (type 1) theta and carbachol-elicited (type 2) theta. During the postprocaine period theta frequency recovered rapidly in contrast to theta amplitude (power). This result applied to the recovery of both the coactivated type 1 and type 2 theta occurring during spontaneous movement and the carbachol-elicited type 2 theta alone. The behavioral results were discussed within the context of Bland's (Prog. Neurobiol. 26, 1-54, 1986) sensorimotor model which posits that hippocampal theta activity recorded during voluntary movement represents the coactivation of a cholinergically mediated sensory processing component and a feedback (possibly serotonergic) motor component. PMID- 8477827 TI - The effects of chronic administration of captopril on the mouse subfornical organ and area postrema. AB - We have studied by morphometric procedures the chronic effect of captopril on the subfornical organ (SFO) and area postrema (AP) of the adult mouse. Oral administration of captopril does not produce any change in the size of individual nuclei of the ependymocytes and neurons in both centers. However, there are other quantitative effects of captopril on the global volume of the SFO and on the neuropil and vascular elements of both the SFO and AP which present a significant increase. It is suggested that this increase is due to metabolic processes at the level of both circumventricular organs. PMID- 8477828 TI - Regenerating axons are not required to induce the formation of a Schwann cell cable in a silicone chamber. AB - After suture of proximal and distal nerve stumps into the ends of a silicone chamber, a tissue cable forms inside the chamber through which axons regenerate. Schwann cells are a critical cellular component of the cable because in their absence axons fail to regenerate into the cable. In this study, we sought to determine whether axons were needed to induce the formation of a Schwann cell containing cable. Transected stumps of sciatic nerves of adult rats were sutured into the ends of silicone chambers prefilled with phosphate-buffered saline or dialyzed plasma, leaving a 10-mm interstump gap. In order to eliminate any axonal influence in the chamber, the proximal sciatic nerve was further transected, ligated, and reflected, leaving a 4-mm piece of denervated nerve in the proximal chamber. A tissue cable formed at 4 weeks only in those chambers prefilled with dialyzed plasma. Light and electron microscopy revealed a central core of Schwann cells and fibroblasts within the cable that were collectively surrounded by a circumferential layer of fibroblasts and collagen. Blood vessels were randomly located throughout the cable. The Schwann cells extended numerous processes that were confined within a basal lamina-like membrane. Many of these processes contained microtubules and resembled unmyelinated axons. The ultrastructure of the processes, however, differed from that of axons in that some of the processes were in direct contact with the basal lamina of the Schwann cells and not surrounded by any other cell extensions. However, since these processes neither stained with silver nor disappeared after transection of the nerves entering or leaving the chamber, we conclude that they are not axons but in fact Schwann cell processes. In other animals bearing 4-week cables, the reflected nerve stump was reattached to the nerve piece in the proximal end of the chamber. Four weeks later, all the cables and varying lengths of the distal nerve trunks were filled with numerous myelinated and unmyelinated axons. The Schwann cell cable that forms within a dialyzed plasma prefilled chamber presents a useful system for basic research concerning the molecular mechanisms of Schwann cell or Schwann cell-axonal interactions and for applied research involving the clinical repair of human peripheral nerve injuries. Since a cable formed by our surgical method supports axonal regeneration, it has the potential to eliminate the need for a nerve graft to repair a gap in a nerve that requires delayed surgical intervention. PMID- 8477829 TI - Differential regenerative growth of CNS axons into tibial and peroneal nerve grafts in the thalamus of adult rats. AB - Segments of peripheral nerve were autografted into the thalamus of adult rats. The peroneal nerve was used in one group, the tibial nerve (which has approximately twice the cross-sectional area of the peroneal nerve) in a second group, and two lengths of peroneal nerve side by side in a third group. Between 1 and 4 months later HRP was applied to the distal end of each graft to label neurons which had regenerated their axons into the graft. Serial coronal sections of each brain were reacted to reveal retrogradely transported HRP, and the positions of all labeled neurons were recorded in camera lucida drawings. In all three groups a few labeled neurons resembling thalamocortical projection cells were found in the dorsal thalamus close to the graft tip (mean number, 29 in the single peroneal group; 22 in the tibial group; and 14 in the double-peroneal group). However, neurons in the thalamic reticular nucleus (TRN) regenerated much more successfully into the larger nerve grafts; many more retrogradely labeled cells were found in animals with tibial or double-peroneal nerve grafts (mean number, 1.1 in the single-peroneal group; 272 in the tibial group; and 163 in the double-peroneal group). These neurons were concentrated in the sector of TRN known to project to the part of the dorsal thalamus containing the graft tip. The largest numbers of labeled neurons were found when the graft tip encroached upon the TRN. These results suggest that both graft size and graft position are critical determinants of the extent of axonal regeneration from the TRN. Larger grafts may be more copiously invaded by regenerating axons because such grafts damage larger numbers of TRN axons when implanted and/or because they stimulate regeneration by releasing critical quantities of neurotrophic factors. PMID- 8477830 TI - Manganese injection into the rat striatum produces excitotoxic lesions by impairing energy metabolism. AB - There is compelling evidence that excessive exposure to manganese (Mn) produces neurotoxicity, especially in the basal ganglia, resulting in a dystonic Parkinsonian disorder. Several experimental or clinical observations suggest that Mn neurotoxicity could involve impairment of energy metabolism. We examined the neurotoxic effects of Mn following local intrastriatal injection. Three hours after the injection of 2 mumol of MnCl2 into rat striatum, ATP levels were reduced to 51% of the control side and lactate level were increased by 97%, indicating an impairment of oxidative metabolism. Neurochemical analysis of the striata 1 week after Mn injection showed changes consistent with a N-methyl-D aspartate (NMDA) excitotoxic lesion. Dopamine, gamma-aminobutyric acid, and substance P concentrations showed dose-dependent significant decreases, but concentrations of somatostatin-like immunoreactivity and neuropeptide Y-like immunoreactivity were unchanged. The lesions were blocked by prior removal of the cortico-striatal glutamatergic input or by treatment with the noncompetitive NMDA antagonist MK-801. These findings indicate that Mn neurotoxicity involves a NMDA receptor-mediated process similar to that we have previously found with two characterized mitochondrial toxins, aminooxyacetic acid, and 1-methyl-4 phenylpyridinium. Our results show that Mn may produce neuronal degeneration by an indirect excitotoxic process secondary to its ability to impair oxidative energy metabolism. PMID- 8477831 TI - Choroidal and iris angioarchitecture of the newt: a scanning electron-microscopic study of vascular corrosion casts. AB - The corrosion cast technique provided for the first time an excellent three dimensional visualization of the vascular pattern of the choroid and iris in the newt eye. The results show the presence of a single arterial afference to the choroidal and iris capillaries: the ophthalmic artery is the origin of both ciliary arteries and the long posterior ciliary artery. Slightly behind the equatorial circumference of the eyeball the venous drainage consists of a single vessel on the dorsal side and two distinct vessels on the ventral one. It receives blood from both iris and choroid. The surface of the plastic endocasts shows some details of fine luminal structures of the endothelial cells. Shallow depressions may be regarded as imprints of endothelial cell nuclei, and they are distinctly different for arteries and capillaries. The angioarchitecture of the newt eye differs from that of brain in that hairpin-shaped capillary loops are not observed at all. PMID- 8477832 TI - Sulfhydryl oxidation induces calcium release from fragmented sarcoplasmic reticulum even in the presence of glutathione. AB - Alcian blue and plumbagin induced transient Ca2+ release from fragmented sarcoplasmic reticulum. Dithiothreitol (DTT) and glutathione (GSH) partially blocked Ca2+ release induced by these oxidizing compounds. Pretreatment of alcian blue and plumbagin with DTT or GSH for more than 1 min was required to abolish the ability of the oxidizing compounds to release Ca2+. Mg2+ and ruthenium red completely blocked alcian blue-and plumbagin-induced Ca2+ release. These results suggest that oxidation of sulfhydryls on Ca2+ release channels induces Ca2+ release even in the presence of GSH in situ. PMID- 8477833 TI - Developmental and ageing changes in aminopeptidase activities in selected tissues of the rat. AB - Aminopeptidase activities, assayed as arylamidase activities, were investigated in selected tissues of 1, 6, 12 and 24-month-old rats. The enzyme activities were found to have a heterogeneous distribution and age-related changes were observed. The highest levels of soluble arginyl-aminopeptidase activity were detected in brain homogenate at all the studied ages, whereas membrane-bound activity presented the highest levels in brain and kidney in the four ages tested. Aspartyl-aminopeptidase activity was detected mainly in the particulate fraction of kidney at all four ages. In 1, 6 and 12-month-old animals, soluble aspartyl aminopeptidase activity was also higher in the kidney than in the rest of the tissues, whereas in the group of 2-year-old rats, the highest levels were found in both kidney and liver. Age-related changes were observed in all the studied tissues and for all the assayed enzymatic activities. In general, the maximal levels were detected in both the youngest and the oldest animals, and the minimal ones in 6 and 12-month-old rats. However, in the adrenals, the soluble and membrane-bound arginyl-aminopeptidase activity was higher in 6-month and 2-year old rats than in 1-month and 12-month-old rats. These changes may reflect the functional status of the susceptible endogenous substrates of aminopeptidases. PMID- 8477834 TI - Free intracellular and protein bound amino acids in tissues as affected by a mixed beta-adrenergic agonist. AB - The administration of metaproterenol induced an increase in gastrocnemius muscle weight without change in body growth rate or tissue protein concentrations, while epididymal fat was reduced. This effect was accompanied by an enhancement in the levels of intracellular amino acids in muscle. By contrast, liver amino acids were unaffected by treatment with the mixed beta-adrenergic agonist. PMID- 8477835 TI - Tissue-specific modulation of rat glucocorticoid receptor binding activity by melatonin. AB - The effect of melatonin and 2-Iodo-melatonin on nuclear and cytosolic glucocorticoid receptors in the brain, pituitary, thymus and liver has been examined. The results indicate that both melatonin and 2-Iodo-melatonin administration is associated with marked changes in the density and the affinity of cytosolic and nuclear forms of glucocorticoid receptors. These observations are discussed in the context of a possible involvement of pineal melatonin in the mechanisms regulating the behaviour and metabolism of steroid receptors. PMID- 8477836 TI - Role of lipid peroxidation in ferric lactate-enhanced calcium uptake by Ehrlich carcinoma cells. AB - Comparison of Ca2+ uptake by Ehrlich carcinoma cells in presence of ferric lactate or aluminum lactate, and formation of thiobarbituric acid-reactive substances, suggests that lipid peroxidation is associated with but not the cause of calcium overload that can lead to cell injury and death. PMID- 8477837 TI - Retroviral-mediated gene therapy for the treatment of citrullinemia. Transfer and expression of argininosuccinate synthetase in human hematopoietic cells. AB - Citrullinemia is a recessive genetic disease caused by a deficiency in argininosuccinate synthetase (AS). Retroviruses were used to transduce the human AS gene into cultured human cells. Using amphotropic viruses with high titer (> 10(6) cfu/ml), we were able to correct the defect in cultured fibroblasts from citrullinemic patients. Retroviral transduction of the human AS gene into human bone marrow cells was also studied. Co-cultivation was used to infect the cells and up to 80% of progenitor cells were found to be carrying and expressing the AS retrovirus after infection. When the infected cells were kept in culture, integration and expression of the retrovirus was observed. Retroviral sequences were present and expressed in the cultured bone marrow-derived cells for up to 10 weeks. PMID- 8477838 TI - Agglutinins from aquatic insects--tumor cell agglutination activity. AB - Agglutinins were identified in whole body extracts of aquatic insects by means of murine tumor cell agglutination, using sarcoma 180 ascites, Ehrlich, and MM-46 cells. Screening revealed agglutinins in 5 of 10 of the larvae tested, and in 2 of 6 of the water-dwelling adult insects; Gerris paludum insularis and Gyrinus japonicus. Only the agglutinin from adult G. paludum also agglutinated human erythrocytes. An ascites tumor was converted into a solid form in vivo after administration of G. paludum agglutinin. The observation that these aquatic insect agglutinins preferentially agglutinate tumor cells has considerable implications in terms of anti-tumor effects such as inhibition of cell proliferation and metastasis. PMID- 8477839 TI - Properties of engineered antifreeze peptides. AB - Eight antifreeze-like peptides were produced by cleavage from engineered chimeric proteins. One was homologous to an antifreeze peptide of the winter flounder; the others differed in length and/or sequence. The homologous peptide and all those of equal or greater length were able to inhibit recrystallization. The longer peptides were so hydrophobic that their identification required modification of the usual protocols for high pressure liquid chromatography. Their elution positions were correlated to their hydrophobicities and their lengths. Additional naturally occurring antifreezes may be identifiable with this knowledge. PMID- 8477840 TI - Control of muscle pyruvate oxidation during late pregnancy. AB - Despite significant increases in circulating concentrations of lipid fuels (triacylglycerol, non-esterified fatty acids (NEFA) and ketone bodies) in late pregnant rats sampled in the fed (absorptive) state, cardiac and skeletal muscle active pyruvate dehydrogenase (PDHa) activities remained comparable with those observed in fed, age-matched virgin controls. Cardiac PDHa activity was suppressed in response to acute (6 h) starvation in late-pregnant (as well as virgin) rats: this inactivation was opposed by inhibition of mitochondrial long chain FA oxidation. Starvation (6 h) also led to PDH inactivation in skeletal muscles of late-pregnant, but not virgin, rats. Starvation for 24 h led to further suppression of cardiac PDHa activity and was associated with significant increases in PDH kinase activities in both virgin and late-pregnant rats. Late pregnancy did not itself influence cardiac PDH kinase activity. PMID- 8477841 TI - Inhibition of neutral cholesteryl ester hydrolase by a naturally occurring cytosolic protein in macrophages. AB - The soluble fraction from a number of macrophage cell lines has been shown to contain a protein(s) that inhibits neutral cholesteryl ester hydrolase. The inhibition is dependent on the concentration of soluble protein used, and the efficiency of the inhibitor can be influenced by the inclusion of oleate and an inhibitor of ACAT. It is suggested that the presence of this material indicates that the macrophage contains a means of negatively controlling the activity of the hydrolytic phase of the cholesterol/cholesteryl ester cycle. PMID- 8477842 TI - Amino acid sequence similarities between low molecular weight endo-1,4-beta xylanases and family H cellulases revealed by clustering analysis. AB - The amino acid sequences of seventeen family G xylanases and the two known family H cellulases have been compared by hydrophobic cluster analysis. A weak but significant similarity was demonstrated between these two families suggesting that these enzymes share the same molecular mechanism and catalytic residues and that they have related 3D folds. The major differences were found in the N terminal regions. PMID- 8477843 TI - Different thyroid hormone-deiodinating enzymes in tilapia (Oreochromis niloticus) liver and kidney. AB - Enzymes catalyzing the outer ring deiodination (ORD) of iodothyronines are important for the regulation of thyroid hormone bioactivity. We have studied ORD of thyroxine (T4) and 3,3',5'-triiodothyronine (rT3) in liver and kidney microsomes of fish, i.e. tilapia (Oreochromis niloticus). Tilapia kidney contains an enzyme which resembles the mammalian selenoenzyme type I iodothyronine deiodinase (ID-I) with respect to substrate preference (rT3 > T4) and high (approximately microM) Km values, but is much less sensitive to selenocysteine (Sec)-targeted inhibitors, including 6-propyl-2-thiouracil (PTU). In contrast, tilapia liver contains an enzyme very similar to mammalian type II deiodinase (ID II) with respect to substrate preference (T4 > rT3), low (approximately nM) Km values, and lack of sensitivity to Sec inhibitors. PMID- 8477844 TI - Divergent effects of fluoroaluminates on the peptide chain elongation factors EF Tu and EF-G as members of the GTPase superfamily. AB - Fluoraluminates are thought to mimic the gamma-phosphate of GTP and thus, together with GDP, perturb the functioning of heterotrimeric GTP-binding G proteins. Here we show they do inhibit the ribosome-stimulated GTPase activity of EF-G from Escherichia coli via the formation of a stable complex with EF-G-GDP and ribosomes. In contrast, no perturbed interactions were observed in a similar ribosomal complex with EF-Tu. Interestingly, in the absence of ribosomes both EF Tu an EF-G remain totally unaffected by fluoraluminates. For members of the GTPase superfamily such differential effects have not been described before. PMID- 8477845 TI - Identification of a protein from Saccharomyces cerevisiae with E2F-like DNA binding and transactivating properties. AB - The promoter of the human proto-oncogene MYC has been the first cellular target shown to be subject to regulation by the E2F transcription factor. E2F also has binding sites in other promoters regulated by cell proliferation and during the cell cycle. We have analyzed Saccharomyces cerevisiae for the presence of an E2F analogous protein. GAL1-based promoter constructs carrying the E2F binding site of the MYC or the adenovirus E2 promoter showed transcriptional activity in yeast cells. A DNA-binding factor, designated YE2F, binds specifically to the E2F consensus sequence and was partially purified from yeast extracts. YE2F showed identical contact points within the MYC binding site as authentic E2F protein from mammalian cells. The results suggest that the existence of an E2F-like protein in the yeast S. cerevisiae. PMID- 8477846 TI - Stabilization of mRNA in an Escherichia coli cell-free translation system. AB - It became clear that mRNA can be stabilized in a cell-free translation system of Escherichia coli by hybridization with a small DNA fragment at its 3' terminus. The stability increased when a small DNA fragment containing a stable hairpin structure with a GAAA loop was used. The enhancement of stabilization was brought about because the hairpin structure is resistant towards the nucleases contained in the translation system. The hairpin structure is effective by stabilizing the added DNA fragment itself towards the nucleases. PMID- 8477847 TI - Regulation of spermidine/spermine N1-acetyltransferase by intracellular polyamine pools. Evidence for a functional role in polyamine homeostasis. AB - Through its role in polyamine acetylation and the back-conversion pathway, spermidine/spermine N1-acetyltransferase (SSAT) has the potential to control intracellular polyamine pools by facilitating their catabolism and/or excretion. The possibility that the enzyme is subject to regulation by intracellular polyamine pools was investigated in MALME-3 human melanoma cells. Increases in intracellular polyamine pools by treatment with 3 microM exogenous spermidine or spermine for 48 h caused SSAT activity to increase 111% and 226%, respectively, and SSAT-specific mRNA to rise 19% and 66%, respectively. Decreases in polyamine pools by treatment with inhibitors of polyamine biosynthesis caused SSAT activity to decrease by 46% and mRNA to fall by 89%. Both SSAT activity and mRNA were more sensitive to changes in spermine than spermidine. The identification of a positive regulatory relationship between SSAT and intracellular polyamine pools further implicates this enzyme in a proposed model for polyamine pool homeostasis. PMID- 8477848 TI - Characterization and regulation of the angiotensin II type-1 receptor (binding and mRNA) in human adrenal fasciculata-reticularis cells. AB - The classical concept of human adrenal physiology indicates that only glomerulosa cells are the target of A-II. Herein, we demonstrated that cultured human adrenal fasciculata-reticularis cells were also responsive to this hormone. Indeed, these cells contained high affinity (Kd = 0.9-1.1 nM) and low capacity (8,000-13,000 sites/cell) A-II receptors, and more than 95% of them were of the type-1. These AT1 receptors are functional since A-II was able to increase cortisol production after 48 h of treatment. These effects were inhibited by losartan, an AT1 antagonist, but not by CGP42112A, an AT2 antagonist. The expression of the type-1 A-II receptor mRNA was detected in the whole adrenal in both adult and fetus, and in cultured human adrenal fasciculata-reticularis cells. In these cells A-II negatively regulated AT1 receptor mRNA, and this effect was also mediated through the AT1 receptor subtype. PMID- 8477849 TI - Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNALeu(UUR) gene. AB - A heteroplasmic point mutation (transition A-to-G at nucleotide position 3,243 in the mitochondrial tRNALeu(UUR) gene) is found in a family suffering from a syndrome with diabetes, deafness and cardiomyopathy as the predominant clinical features. PMID- 8477850 TI - Insertion of MOM22 into the mitochondrial outer membrane strictly depends on surface receptors. AB - Targeting of preproteins to mitochondria and their translocation across the outer membrane are mediated by the mitochondrial receptor complex. This protein complex contains the import receptors MOM19 and MOM72 and the general insertion pore GIP. All seven components of the receptor complex are synthesized in the cytosol and thus have to be targeted to the mitochondria themselves. Here we investigated the import pathway of the precursor of MOM22 into the outer membrane. In contrast to other mitochondrial preproteins studied so far, the import of MOM22 absolutely depended on the presence of surface receptors. In fact, both receptors MOM19 and MOM72 were involved in its import pathway. The targeting of MOM22 to mitochondria is thus highly specific and controlled. PMID- 8477851 TI - Human neuroblastoma cells produce the NF-kappa B-like HIV-1 transcription activator during differentiation. AB - Human neuroblastoma GOTO and IMR32 cells differentiate into neural cells on treatment with 5-BrdU. Here we report that in association with differentiation induced by 5-BrdU, the transcription of HIV-1 was activated in both neuroblastoma cell lines. An NF-kappa B-like factor was also found to be produced in association with the neural cell differentiation of these cells. These results suggest that, during differentiation of neural cells, an NF-kappa B-like factor was produced, and that when the neural cells are infected with HIV-1 the production of NF-kappa B results in activation of transcription of HIV-1. Thus this NF-kappa B-like factor may be involved in the mechanism causing AIDS dementia. PMID- 8477853 TI - Prostaglandin A2 and delta 12-prostaglandin J2 induce apoptosis in L1210 cells. AB - Treatment of L1210 cells with prostaglandin A2 (PGA2) or 9-deoxy-delta 9,12-13,14 dihydro PGD2 (delta 12-PGJ2) resulted in significant G2/M arrest and subsequent DNA fragmentation at concentrations that are cytotoxic to the cells. On agarose gel electrophoresis, DNA ladder formation was evident 24 h after the addition of delta 12-PGJ2 and remained apparent through 72 h, whereas G2/M accumulation was observed 6 h after the treatment. When the morphology of cells was examined by electron microscopy, L1210 cells incubated with a cytotoxic dose of PGA2 or delta 12-PGJ2 for 24 h showed the characteristic morphological features of apoptosis such as chromatin condensation, nuclear fragmentation and formation of apoptotic body. Cycloheximide blocked the DNA fragmentation and morphological changes induced by delta 12-PGJ2. Our results suggest that these cyclopentenone PGs caused apoptotic cell death of L1210 cells which is preceded by G2/M accumulation and requires de novo protein synthesis. PMID- 8477852 TI - Prostaglandin H synthase. Inactivation of the enzyme in the course of catalysis is accompanied by fast and dramatic changes in protein structure. AB - Prostaglandin H synthase (PGHS) as apo-PGHS, holo-PGHS, and holo-PGHS, inactivated in the course of catalysis was studied using chemical modification with diethyl pyrocarbonate (DEPC). The exhausted reaction with DEPC corresponded to the modification of 7 histidine residues in apo-PGHS and 4 in holo-PGHS. All 18 histidine residues became accessible for modification with DEPC in the enzyme, inactivated in the course of catalysis. The velocities of tryptic cleavage of all the three forms into two fragments were fairly different but independent of modification. Based on the results we hypothesize fast and dramatic changes in the protein structure in the course of the substrate conversion. PMID- 8477854 TI - Time-resolved tryptophan fluorescence in photosynthetic reaction centers from Rhodobacter sphaeroides. AB - Tryptophan fluorescence of reaction centers isolated from Rhodobacter sphaeroides, both stationary and time-resolved, was studied. Fluorescence kinetics were found to fit best a sum of four discrete exponential components. Half of the initial amplitude was due to a component with a lifetime of congruent to 60 ps, belonging to Trp residues, capable of efficient transfer of excitation energy to bacteriochlorophyll molecules of the reaction center. The three other components seem to be emitted by Trp ground-state conformers, unable to participate in such a transfer. Under the influence of intense actinic light, photooxidizing the reaction centers, the yield of stationary fluorescence diminished by congruent to 1.5 times, while the number of the kinetic components and their life times remained practically unchanged. Possible implications of the observed effects for the primary photosynthesis events are considered. PMID- 8477855 TI - The ZNF35 human zinc finger gene encodes a sequence-specific DNA-binding protein. AB - We developed a rapid method to determine DNA-binding sites for putative DNA binding proteins. This procedure has been successfully used to define a specific consensus site for the human ZNF35 zinc finger gene. ZNF35 encodes a 58-kDA polypeptide containing 11 consecutive finger motifs located at the amino terminus, and an acidic domain located at the carboxy terminus. These features suggest that ZNF35 is a site-specific DNA-binding protein involved in the regulation of gene expression. We have expressed the ZNF35 protein from E. coli and have employed a Southwestern-polymerase chain reaction method using random oligonucleotides to identify its high-affinity binding site. The core sequence for the ZNF35 protein-binding site is 5'-C/GC/GAAG/TA-3'. PMID- 8477856 TI - Domain of E. coli translational initiation factor IF2 homologous to lambda cI repressor and displaying DNA binding activity. AB - The carboxy-terminal region of translational initiation factor IF2 is a common region to the three active forms of the factor (alpha, beta and gamma) but its function is still unknown. We report here that this region of IF2 carries at least one domain which is homologous to the N-terminal and middle part of the cI repressor of lambda phage. The IF2 homologous domain harbors functionally important features of the lambda repressor, e.g. the helix-turn-helix motif and some of the residues essential for the structure of the hydrophobic core of the repressor. This homologous domain of IF2 was fused to the beta-galactosidase protein. The hybrid protein, as well as IF2 itself, shows a consistent DNA binding activity in nitrocellulose filtration assays but does not display the specificity of the cI repressor for the PR operator. The implication of this domain in the transcriptional activity of IF2, reported by others, is discussed. PMID- 8477857 TI - Participation of cathepsin L on bone resorption. AB - The proteinase responsible for bone collagen degradation in osteo-resorption was examined. The bone pit formation induced by parathyroid hormone (PTH) was markedly suppressed by leupeptin, E-64 and cystatin A, while no inhibition was observed by CA-074, a specific inhibitor of cathepsin B. Pig leucocyte cysteine proteinase inhibitor (PLCPI), a specific inhibitor of cathepsin L, and chymostatin, a selective inhibitor of cathepsin L, completely inhibited the pit formation. Cathepsin L activity in osteoclasts was much higher than the other cathepsin activities. Serum calcium in rats placed on a low calcium diet was decreased by treatment of E-64 or cystatin A, but not by CA-074. These findings suggest that cathepsin L is the main proteinase responsible for bone collagen degradation. PMID- 8477858 TI - Structure and localization of mRNA encoding a pigment dispersing hormone (PDH) in the eyestalk of the crayfish Orconectes limosus. AB - The pigment-dispersing hormone (PDH) is produced in the eyestalks of Crustacea where it induces light-adapting movements of pigment in the compound eye and regulates the pigment dispersion in the chromatophores. To study this hormone at the mRNA level, we cloned and sequenced cDNA encoding PDH in the crayfish Orconectes limosus. The structure of the PDH preprohormone consists of a signal peptide, a PDH precursor-related peptide (PPRP) and the highly conserved PDH peptide at the carboxy-terminal end. In situ hybridization in combination with immunocytochemistry revealed four cell clusters expressing PDH in the optic ganglia of the eyestalk. Three clusters stained both with the PDH cRNA probe and the PDH antiserum, however, the perikarya in the lamina ganglionaris (LG) only stained with the PDH antiserum, suggesting the presence of a PDH-like peptide in the LG. PMID- 8477859 TI - The catalytic activities of monomeric enzymes show complex pressure dependence. AB - High hydrostatic pressures in the biologically relevant range (< or = 1,200 bar) are known to cause dissociation of oligomeric enzymes in vitro, whereas protein denaturation requires pressures far beyond this range. Pressure-induced inactivation phenomena attributable to neither of these effects are shown to occur in monomeric enzymes. Three different types of pressure dependence can be distinguished: (1) a linear dependence of catalytic rate constants on pressure, as predicted by the activated complex theory, observed for lysozyme and thermolysin; (2) a biphasic profile consisting of two linear contributions, found for trypsin; (3) maximum curves, as observed for both directions of the octopine dehydrogenase reaction. The third case may be ascribed to a pressure-induced decrease in the partial specific volume of the protein, resulting in reduced flexibility of the active site. This mechanism may also apply to the pressure induced inactivation of assembly systems stabilized against dissociation in the cell. PMID- 8477860 TI - Nuclear protein transport is functionally conserved between yeast and higher eukaryotes. AB - The ability of a yeast nuclear protein to be transported into the nucleus of a higher eukaryotic cell was investigated. Mcm1, a transcriptional activator protein from Saccharomyces cerevisiae, was microinjected into the cytoplasm of Xenopus laevis frog oocytes. Mcm1 was imported into the oocyte nucleus indicating that the machinery for nuclear transport is conserved from yeast to higher eukaryotes. Furthermore, by comparing the nuclear import of free proteins and protein-gold complexes, we found that protein-gold complex formation appears to partially and specifically inactivate the nuclear transport activity of Mcm1 and that nucleoplasmin is an exceptionally good nuclear import substrate. PMID- 8477861 TI - The structure of neutrophil defensin genes. AB - Defensins are a family of microbicidal peptides abundant in the granules of mammalian neutrophils, in rabbit alveolar macrophages, and in human and murine intestinal Paneth cells. We cloned and sequenced the genes of three neutrophil specific defensins. Human HNP-1 and HNP-3 are nearly identical and rabbit NP-3a is closely related. The four known neutrophil-specific defensin genes are strikingly similar in the structure and organization of their three exons and two introns, but the three defensin genes expressed in macrophages (MCP-1 and -2) or Paneth cells (HD-5) are organized differently: HD-5 had only two exons, and MCP-1 and -2 have a comparatively short first intron. The diverse genomic organization of defensin genes may contribute to their cell-specific expression. PMID- 8477862 TI - Inactivation of synovial fluid alpha 1-antitrypsin by exercise of the inflamed rheumatoid joint. AB - alpha 1-Antitrypsin (alpha 1AT) is known to be oxidised by reactive oxygen species both in vitro and in vivo, leading to its inactivation. We report here that synovial fluid (SF) alpha 1AT is inactivated during exercise of the knee joints of rheumatoid arthritis (RA) patients. Sequential SF sampling from exercised RA patients showed a marked decrease in the mean activity of alpha 1AT after exercise with no change in the molecular forms of alpha 1AT. No such inactivation was found in the control (continuously resting) RA patients. We suggest that oxidation may contribute to alpha 1AT inactivation as a consequence of 'hypoxic-reperfusion' injury after exercise of the inflamed joint. PMID- 8477863 TI - Surgical crown lengthening for function and esthetics. AB - Clinical crown lengthening is a useful procedure to provide tooth length for proper restoration of a tooth without compromising the periodontium or the retentive qualities of the restoration. It is also useful for enhancing maxillary anterior esthetics. Crown lengthening may be as simple as a limited removal of soft tissue or as complex as orthodontic extrusion followed by flap with osseous surgery on a tooth requiring endodontic therapy. Total treatment could thus involve endodontic, orthodontic, periodontic, and restorative procedures. Careful evaluation, case selection, treatment planning, and surgical treatment following the principles outlined in this article can achieve results that meet the functional and esthetic challenges of current dental practice. PMID- 8477864 TI - Surgical and orthodontic management of impacted teeth. AB - This article has accomplished four objectives. First of all, the most commonly impacted teeth have been identified. Aside from the third molars, these teeth include the maxillary canines, maxillary central incisors, mandibular second premolars, and mandibular second molars. Second, the cause of impaction has been discussed. In most situations, these unerupted teeth have been diverted or are angulated aberrantly during development. Once the root apex has closed, they lose their potential to erupt. Third, the various surgical procedures to uncover these impacted teeth have been described. Three different techniques (excision, apically positioned flap, and closed eruption technique) may be used to uncover the impacted tooth. The specific criteria used to select the proper surgical technique were stated. Last, the orthodontic mechanics and integration of tooth movement and surgical procedures were delineated and illustrated for each of the various types of impactions and uncovering techniques. PMID- 8477865 TI - Soft-tissue surgery to alleviate orthodontic relapse. AB - This article has presented three soft-tissue surgical techniques that have been shown to alleviate the relapse of orthodontically treated teeth in three specific situations: (1) rotations (and possibly also labiolingual irregularities), (2) extraction site closures, and (3) maxillary midline diastemas. The anatomy and histophysiology of the periodontium have been discussed briefly as they pertain to the rationale for these surgical procedures. None of the techniques discussed, if performed as indicated, will be detrimental to the supporting periodontal tissues and all can easily become a routine part of the clinician's standard retention therapy. PMID- 8477866 TI - Free gingival grafts. Current indications and techniques. AB - The free gingival graft is a simple, predictable technique for increasing the zone of attached gingiva. Dentists interested in performing minor surgical procedures should include the free gingival graft in their armamentarium. Indications and contraindications have been established, but the decision regarding the adequacy of the attached gingiva remains one of clinical judgment. The clinician must evaluate several variables, including the width of the attached gingiva, the patient's age, recession history, oral hygiene practices, teeth involved, and dental records. In the opinion of the authors, the free gingival graft usually should not be used in areas of inadequate attached gingiva when root coverage is indicated. Other techniques are more predictable and yield a more esthetic result. PMID- 8477867 TI - The subepithelial connective tissue graft for treatment of gingival recession. AB - A technique has been described for areas of single or multiple root coverage, especially in the maxilla, for coverage of existing crown margins, and for areas requiring a combination of ridge augmentation and root coverage. The success of the subepithelial connective tissue graft is attributed to the double blood supply at the recipient site from the underlying connective tissue base and the overlying recipient flap. The donor site is a closed wound, which produces less postoperative discomfort. In addition, an excellent color blend can be achieved. PMID- 8477868 TI - Treatment of moderate localized alveolar ridge defects. Preventive and reconstructive concepts in therapy. AB - A conscious effort should be made at the time of tooth extraction to eliminate or lessen the creation of a defect within the residual alveolar ridge. This objective can be achieved if teeth are extracted in an atraumatic manner and appropriate implant materials are placed into the sockets to prevent the eventual collapse of the ridge. Guided tissue regeneration procedures also may be used to prevent collapse within the ridge or augment an existing defect. In many instances, deformed ridges can be augmented to their former dimensions by the use of pouch, interpositional, or onlay graft procedures. Case reports are presented to show the effectiveness of these procedures. PMID- 8477869 TI - Laser in dentistry. Soft-tissue procedures. AB - Dentistry has entered the 1990s, an era of high technology. The dental laser offers the dentist not only a window, but a door into this high-tech arena. All of the advantages lasers offer, from bloodless procedures to minimal postoperative pain and from reduction of operative time to high patient acceptance, indicate that lasers are great dental instruments for today and the future. As a futuristic idea, the ideal laser for dentistry would be able to work well, not only in soft tissue, but in hard tissue. Envision a laser with multiple wavelengths in the same unit: one for incision, another for removal of hard tissue, and yet still another for making tissue "sticky" for flap placement and tissue welding. So often dentists are associated with pain, fear, and the noise of the high-speed drill. The laser certainly helps to dispel these stereotypes and apprehensions, and to bring dentistry into a new era. PMID- 8477870 TI - The central nervous system in potassium homeostasis. AB - There is considerable evidence that the central nervous system (CNS) is significantly involved in potassium homeostasis: (a) Potassium-specific receptors located in the liver or hepatic portal circulation initiate a reflex increase in potassium excretion via vagal afferents. This reflex is lost or diminished with hypophysectomy. (b) Oscillators, presumably located in the hypothalamus, determine a circadian rhythm in the renal excretion of potassium. The efferent control factors are unknown. (c) Exogenous hypophysial peptides (vasopressin, oxytocin, and alpha-, beta-, and gamma-MSH) stimulate increased potassium (and sodium) excretion. (d) Hypophysial gamma-MSH or a related hypophysial peptide stimulates an increase in the excretion of potassium (and sodium) following uninephrectomy in the rat. This adaptive response involves cerebral, naloxone inhibitable opioid receptors. (e) Intra-third-ventricular infusion of hypertonic NaCl initiates an increased potassium (and sodium) excretion through undetermined humoral mechanisms and is blocked by prior hypophysectomy. (f) In rats depleted of potassium by low potassium intake or by production of DOCA hypertension, an inhibition of skeletal muscle Na+, K(+)-ATPase ion pump activity is directed by hypothalamic centers and involves inhibition by alpha-adrenergic activity of slow twitch fibers and inhibition by undetermined humoral factors of fast twitch fibers. (g) Potassium receptors, either demonstrated or inferred, initiate reflex increases in respiration, heart rate, blood pressure, and peripheral tissue potassium uptake as well as a reflex inhibition of skeletal muscle ion pumps. (h) Evidence for CNS regulation of potassium intake is equivocal. Major gaps exist in this emerging picture of neuroendocrine involvement in potassium homeostasis. PMID- 8477871 TI - Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture. AB - In order to explore the possible contribution of insulin-like growth factor I to the development of diabetic nephropathy, the effect of glucose on the mitogenic and metabolic actions of insulin-like growth factor I in cultured rat glomerular mesangial cells was examined. The stimulation of [3H]-thymidine incorporation by insulin-like growth factor I in the cells exposed to high concentrations (55 mmol/l) of glucose (4.6 +/- 1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/l glucose (17.5 +/- 0.8 fold). In contrast, [3H]-amino-isobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03 +/- 0.03 nmol.mg protein-1. 15 min-1 at 55 mmol/l glucose vs 0.59 +/- 0.01 at 11 mmol/l glucose), while 2-deoxyglucose uptake remained unchanged. [125I]-insulin-like growth factor I binding was slightly but significantly increased in the cells exposed to high concentrations of glucose. Thus, glucose may modulate the mitogenic and metabolic actions of insulin-like growth factor I differently in cultured mesangial cells probably at the post-insulin-like growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor I by glucose could result in the increase in amino acid uptake and decrease in the cell proliferation in the mesangial cells, possibly leading to enhanced mesangial matrix synthesis with a relatively small increase in mesangial cell volume as seen in diabetic nephropathy. PMID- 8477872 TI - Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. AB - Liver insulin resistance and glucagon-stimulated hepatic glucose production are characteristics of the diabetic state. To determine the potential role of glucose toxicity in these abnormalities, we examined whether phlorizin treatment of streptozotocin-diabetic rats resulted in altered expression of genes involved in key steps of hepatic glucose metabolism. By inhibiting renal tubular glucose reabsorption, phlorizin infusion to diabetic rats induced normoglycaemia, did not significantly alter low circulating insulinaemia, but caused a marked decrease in hyperglucagonaemia. Glucokinase and L-type pyruvate kinase mRNA levels were reduced respectively by 90% and 70% in fed diabetic rats, in close correlation with changes in enzyme activities. Eighteen days of phlorizin infusion partially restored glucokinase mRNA and activity (40% of control levels), but had no effect on L-type pyruvate kinase mRNA and activity. In contrast to the glycolytic enzymes, mRNA and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase were increased (10- and 2.2-fold, respectively) in fed diabetic rats. Phlorizin administration decreased phosphoenolpyruvate carboxykinase mRNA to values not different from those in control rats, while phosphoenolpyruvate carboxykinase activity remained 50% higher than that in control rats. The 50% rise in liver glucose transporter (GLUT 2) mRNA and protein, produced by diabetes, was also corrected by phlorizin treatment. In conclusion, we propose that phlorizin treatment of diabetic rats may induce a partial shift of the predominating gluconeogenesis, associated with hepatic glucose overproduction, into glycolysis, by correction of impaired pre-translational regulatory mechanisms. This could be essentially mediated through improved pancreatic alpha cell function and subsequent lowering of hyperglucagonaemia. These observations suggest that glucagon-stimulated hepatic glucose production may result, in part, from glucose toxicity. PMID- 8477873 TI - Anti-oxidant treatment prevents the development of peripheral nerve dysfunction in streptozotocin-diabetic rats. AB - We tested the notion that oxidative stress makes an important contribution to the aetiology of diabetic neuropathy. The effect of treatment with a 1% dietary supplement of the anti-oxidant butylated hydroxytoluene was studied during 2 months of streptozotocin-induced diabetes mellitus. In final experiments, sciatic motor and saphenous sensory conduction velocities were measured in vivo, and resistance to hypoxic conduction failure for sciatic trunk was examined in vitro. There were 20% and 12% decreases in motor and sensory conduction velocity, respectively after 2 months of diabetes (p < 0.001). There were completely prevented by butylated hydroxytoluene treatment (p < 0.001). Resistance to hypoxic conduction failure, shown by the time taken for sciatic compound action potential amplitude to decline by 80%, was 55% increased by diabetes, and this was limited to 31% (p < 0.01) by treatment. There were no significant effects of treatment on the 9-10 fold elevation of sciatic nerve sorbitol and fructose levels with diabetes, or on the non-significant 22% reduction in myoinositol content. Butylated hydroxytoluene treatment also did not affect sciatic nerve capillary density. We conclude that oxidative stress makes an important contribution to the aetiology of early experimental diabetic neuropathy. Amelioration of oxidative stress could potentially be a final common mechanism whereby a number of diverse treatments exert a beneficial effect on diabetic nerve function. PMID- 8477874 TI - Preferential alteration of oxidative relative to total glycolysis in pancreatic islets of two rat models of inherited or acquired type 2 (non-insulin-dependent) diabetes mellitus. AB - In islets from both adult rats injected with streptozotocin during the neonatal period and spontaneously diabetic rats obtained by repeated selective breedings (GK rats), the ratio between D-[3,4-14C]glucose oxidation and D-[5-3H]glucose conversion to 3HOH was 25% lower than in islets from control rats, indicating an impaired contribution of oxidative to total glycolysis. No primary defect in the Krebs cycle was found in the islets of diabetic rats, as judged from the ratio between either D-[2-14C]glucose or D-[6-14C]glucose and D-[3,4-14C]glucose oxidation. Therefore, we propose that a preferential alteration of oxidative glycolysis in the pancreatic beta cell may contribute to the impairment of glucose-induced insulin release not only in a cytotoxic but also in a spontaneous model of non-insulin-dependent diabetes mellitus. PMID- 8477875 TI - Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats. AB - Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6-10 mmol/l or 10-20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10-15% following short- and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p = 0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p = 0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r = -0.60, p < 0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion. PMID- 8477876 TI - Distribution of glycosaminoglycans in the intima of human aortas: changes in atherosclerosis and diabetes mellitus. AB - Arterial glycosaminoglycans are considered to be important in atherogenesis due to their ability to trap lipid inside the vessel wall and to influence cellular migration and proliferation. Atherosclerotic lesions have displayed an altered glycosaminoglycan content and distribution. Diabetes is a recognized risk factor for atherosclerosis, but no information is available on the arterial glycosaminoglycans in human diabetes. We examined glycosaminoglycans in normal and atherosclerotic intima of non-diabetic and Type 2 (non-insulin-dependent) diabetic patients. Intima was stripped from autopsy samples of thoracic aortas; normal and plaque areas were separated. Glycosaminoglycans were isolated by delipidation, proteolytic digestion, and precipitation and characterized by quantitation of total glycosaminoglycan and evaluation of glycosaminoglycan distribution by electrophoresis and densitometry. Results indicate a significant decrease in total glycosaminoglycan and significant changes in their distribution in atherosclerotic plaques: a relative decrease in heparan sulphate, a relative increase in dermatan sulphate and thus a decrease in the ratio of heparan sulphate to dermatan sulphate. A similar but less marked change in the ratio was found in normal intima of diabetic subjects, while in their plaques this change was more pronounced. This suggests that changes in arterial glycosaminoglycans (especially the ratio of heparan sulphate to dermatan sulphate) precede the development of lesions in diabetes and may be important in atherogenesis. PMID- 8477877 TI - Islet amyloid polypeptide: demonstration of mRNA in human pancreatic islets by in situ hybridization in islets with and without amyloid deposits. AB - Islet amyloid polypeptide which is normally coexpressed with insulin in beta cells, forms amyloid deposits especially in islets of Type 2 (non-insulin dependent) diabetic subjects. Occurrence of islet amyloid is paradoxically associated with loss of islet amyloid polypeptide immunoreactivity in beta cells. The present study was undertaken to examine whether the islet amyloid polypeptide gene is expressed in islets with decreased islet amyloid polypeptide immunoreactivity. Pancreatic tissue from 14 patients, 7 with Type 2 diabetes and 7 non-diabetic, were obtained at autopsy or surgery and studied for islet amyloid polypeptide expression by in situ hybridization and for presence of insulin and islet amyloid polypeptide by immunohistochemistry. Six of the specimens from the diabetic and three of those from the non-diabetic patients had varying degrees of islet amyloid polypeptide-derived islet amyloid. Amyloid deposits were associated with decreased numbers of beta cells with islet amyloid polypeptide immunoreactivity despite an apparent normal frequency of insulin-containing cells. This discrepancy might reflect an alteration in islet amyloid polypeptide production or processing at a transcriptional or post-transcriptional level. In contrast to the varying immunohistochemical patterns, islets of all categories showed strong labelling using an islet amyloid polypeptide probe for in situ hybridization. It is concluded that islet amyloid polypeptide production is not altered at the transcriptional level. The following possibilities remain: (1) islet amyloid polypeptide production may be altered at a post-transcriptional level or (2) that islet amyloid polypeptide production is normal but the reduced immunoreactivity of the cells reflects a reduced storage of IAPP in secretory granules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477879 TI - Human insulin receptor substrate-1 gene (IRS1): chromosomal localization to 2q35 q36.1 and identification of a simple tandem repeat DNA polymorphism. AB - The protein designated as insulin receptor substrate-1 (IRS-1) is a major substrate for the insulin receptor tyrosine kinase. Since post-receptor defects in the insulin signalling pathway are a common feature of Type 2 (non-insulin dependent) diabetes mellitus, we have cloned the human IRS-1 gene in order to study the role of genetic variation in this gene in the pathogenesis of diabetes mellitus. As a first step in these studies, we have mapped the IRS-1 gene to chromosome 2, bands q35-q36.1 and identified a simple tandem repeat DNA polymorphism in this gene that will be useful for genetic studies. PMID- 8477878 TI - Cognitive dysfunction in adults with type 1 (insulin-dependent) diabetes mellitus of long duration: effects of recurrent hypoglycaemia and other chronic complications. AB - To examine the long-term effects of recurrent severe hypoglycaemia and other biomedical complications on mental efficiency, a battery of cognitive tests was administered to 142 Type 1 (insulin-dependent) diabetic adult patients (age 33.5 +/- 5.6 years; mean +/- SD) and 100 demographically similar non-diabetic control subjects. All diabetic subjects had been diagnosed before the age of 17 years. Diabetic subjects with one or more complications (distal symmetrical polyneuropathy; advanced background or proliferative retinopathy; overt nephropathy; one or more episodes of severe hypoglycaemia) performed significantly (p < 0.001) more poorly than non-diabetic control subjects on tests requiring sustained attention, rapid analysis of visuospatial detail, and hand eye co-ordination. Regression analyses indicated that the best biomedical predictor of cognitive test performance was a diagnosis of polyneuropathy. Although severe recurrent hypoglycaemia was not associated with performance on any test, the neuropathy x recurrent hypoglycaemia interaction term was significant. These results suggest that in adults with Type 1 diabetes of long duration, recurrent hypoglycaemia does not appear to influence cognitive performance directly, but may interact with neuropathy to exaggerate or otherwise magnify the extent of neurobehavioural dysfunction. PMID- 8477880 TI - The contribution of naturally labelled 13C fructose to glucose appearance in humans. AB - Among monosaccharides, fructose has a small hyperglycaemic effect. In order to better explain the mechanisms which cause this metabolic property, we used tracers labelled with stable isotopes (deuterated glucose and naturally 13C labelled fructose) to quantify the overall glucose appearance, the rate of appearance in plasma of the 13C glucose synthesized from fructose, and the fructose oxidation in vivo in man during a 6-h period following ingestion of 0.5 and 1 g.kg-1 fructose. Fructose had a very small effect on overall glucose appearance (NS). During the 6 h of the study, it was found that the overall glucose appearance was 0.87 +/- 0.06 and 0.89 +/- 0.06 g.kg-1 (NS). The amount of glucose synthesized from fructose was 0.27 +/- 0.04 and 0.51 +/- 0.03 g.kg-1 (p < 0.01) representing 31% and 57% of overall glucose appearance (p < 0.01); the non fructose glucose production was 0.60 +/- 0.02 and 0.38 +/- 0.03 g.kg-1 (p < 0.05) after the 0.5 and 1 g.kg-1 load, respectively. Fructose oxidation was 0.28 +/- 0.03 and 0.59 +/- 0.07 g.kg-1 after the 0.5 and 1 g.kg-1 load respectively (p < 0.01) representing 56% and 59% of the fructose loads (NS). These data show that the low hyperglycaemic effect of fructose is explained by its very small effect on overall glucose appearance and that fructose has a sparing effect on glucose metabolism. PMID- 8477881 TI - Both acute and chronic near-normoglycaemia are required to improve insulin resistance in type 1 (insulin-dependent) diabetes mellitus. AB - To determine the impact of both short- and long-term "near-normoglycaemia" on insulin resistance in Type 1 (insulin-dependent) diabetes hepatic glucose production (mg.kg-1.min-1) and peripheral glucose utilisation ("M-value", mg.kg 1.min-1) were estimated during an euglycaemic hyperinsulinaemic clamp (10 mU.kg.min) in patients with either good (HbA1c < 5.8%, groups A and B) or poor (HbA1c > 7.5%, groups C and D) long-term metabolic control (time > 12 months) and in healthy subjects (HbA1c: 5.08 +/- 0.20%; n = 8). To this end blood glucose was stabilized at 6.7 mmol/l by overnight (t = 12 h) i.v. regular insulin in groups (n = 8 each) A (HbA1c: 5.49 +/- 0.46%) and C (HbA1c: 8.83 +/- 1.20%), while groups B (HbA1c: 5.55 +/- 0.19%) and D (HbA1c: 8.51 +/- 1.09%) were kept overnight on long-acting insulin without feed-back control of blood glucose before euglycaemic clamping. Thereby, pre-equilibration of blood glucose at 6.7 mmol/l was shown to normalize basal hepatic glucose production (A: 2.27 +/- 0.48; C 2.50 +/- 0.57 mg.kg-1.min-1) despite different HbA1c values, whereas basal hepatic glucose production stayed elevated in groups B (3.09 +/- 0.38 mg.kg-1.min 1) and D (3.21 +/- 0.58 mg.kg-1.min-1) with poor actual glycaemia (B: 10.9 +/- 4.6; D: 12.1 +/- 4.6 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477882 TI - Human pancreatic islet function at the onset of type 1 (insulin-dependent) diabetes mellitus. AB - Viable human pancreatic islets isolated from a recent-onset Type 1 (insulin dependent) diabetic patient were used to perform in vitro studies. Pre-proinsulin mRNA and insulin content, as well as insulin response were analysed. Insulin response to glucose and forskolin was completely absent in diabetic islets, as compared to control islets. Insulin content was reduced to only one-third of control values (395.0 +/- 3.5 vs 989.0 +/- 46.3 microU/islet) and 20.7 +/- 3.9% of islets from the diabetic pancreas contained insulin-positive cells in immunofluorescence studies. Northern blot analysis revealed a severe reduction in the content of pre-proinsulin mRNA in diabetic pancreatic tissue. Our results indicate that although markedly decreased, beta cells in human pancreatic islets at the onset of Type 1 diabetes are still present. Nevertheless, pancreatic islet function is disproportionately impaired with a complete absence of an insulin response. PMID- 8477883 TI - Plasma disappearance of glycated and non-glycated albumin in type 1 (insulin dependent) diabetes mellitus: evidence for charge dependent alterations of the plasma to lymph pathway. AB - The fractional plasma escape rates of glycated and non-glycated albumin have earlier been measured in groups of Type 1 (insulin-dependent) diabetic patients and control subjects. The escape of non-glycated albumin was similar in control subjects and normoalbuminuric patients, but elevated in patients with micro or macroalbuminuria. In all groups the escape rate of glycated albumin was lower than that of non-glycated albumin. Glycation increases the anionic charge of albumin. To assay for charge-dependent alterations of transport a selectivity index (non-glycated albumin/glycated albumin transport ratio) was determined from the disappearance data. The index was high in control subjects (1.021 +/- 0.0057 (SEM)). This reflects a mean difference between the two escape rates of 2.1% per hour (for comparison the mean of the fractional escape rate of non-glycated albumin of the normal control subjects was 4.7% per hour). The index was numerically even higher in normoalbuminuric patients (1.031 +/- 0.0047 (SEM)), but reached significantly lower levels in patients with microalbuminuria (1.013 +/- 0.0030 (SEM), p < 0.02). Patients with clinical nephropathy had very low levels indicating loss of selectivity (1.002 +/- 0.0068 (SEM), p < 0.001). This pattern accords well with measurements of renal clearance selectivity indices, suggesting a general, progressive deterioration of anionic perivascular barrier components in diabetic microangiopathy. The structural target for these changes is likely to be the glycosaminoglycans of the glomerular basal membrane and the interstitial matrix. PMID- 8477884 TI - A model for the involvement of MHC class II proteins in the development of type 1 (insulin-dependent) diabetes mellitus in response to bovine serum albumin peptides. PMID- 8477885 TI - Nicotinamide and insulin sensitivity. PMID- 8477886 TI - HIV infection and Norwegian general practitioners: does fear affect knowledge? AB - The objective was to study the dimensionality of knowledge among general practitioners in Norway about transmission of HIV and what factors influence the degree of knowledge. Data were collected by a mailed questionnaire. Independent variables were experience of HIV, acquisition of knowledge and confidence in information on HIV from the central authorities and perception of own knowledge, skills of practice and fear of oneself or one's family contracting the HIV infection. Analysis of variance and multiple classification analysis were applied to measure the effect of independent variables on knowledge about transmission of HIV. The general practitioners in three counties (Oslo, More og Romsdal and Troms), constituting one-quarter of the Norwegian general practitioner population were selected (n = 578). The response rate was 65%, and the results are assumed to be representative of Norwegian general practitioners. Four dimensions of knowledge about transmission of HIV were identified by factor analysis. The two most important, transmission through 'body fluids' and transmission by 'needle sticks', were subsequently converted into sum scores and used as dependent variables. Forty-five per cent of the respondents were uncertain about ways in which HIV is not transmitted through 'body fluids'. There was an association between knowledge about transmission through 'body fluids' and the variables county background, confidence in the information about HIV and fear of contracting HIV. In the multiple classification analysis these three variables explained 11% of the variation in knowledge about transmission through 'body fluids'. Only confidence and fear significantly predicted the degree of knowledge, and among the 11% who had no confidence in the information received the effect of fear on knowledge increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477887 TI - Service delivery for people with chronic fatigue syndrome: a pilot action research study. AB - Chronic fatigue syndrome (CFS) is a symptom complex which while mild in some cases is severely debilitating in others. Long-term ill health leads to greater use of resources but in the case of long-term CFS the anecdotal evidence suggested a low compliance with the available options and a high level of both patient and general practitioner dissatisfaction. This pilot study sought through repeated action research cycles to start to identify culturally and contextually sensitive forms of language and models for service delivery suitable for people with CFS in a general practice setting. It worked through a number of action research cycles, to initiate the identification of conceptual models acceptable to both doctors and to patients suffering from CFS, self-management options which encouraged the body's ability to heal itself and services and delivery mechanisms which met patient needs within health provider options. PMID- 8477888 TI - Childhood chickenpox: its impact on child and family. AB - Sixty-nine parents took part in nine discussion groups designed to explore the effect of childhood chickenpox on the behaviour of the affected child, on family routines and on the parents themselves. Although most parents thought of chickenpox as a relatively trivial illness, it was found that there was considerable disruption to family organization and plans and, often, great strain was imposed on a parent, usually the mother. Some families incurred extra financial burdens in terms of time taken from work, the purchase of over the counter preparations, childminders and special treats for the sick child. It was apparent that parents needed more information and reassurance about the nature and course of the illness. PMID- 8477889 TI - Expectations disease: a model for understanding stress, control and dependent behaviour. AB - Most issues of emotional health seen in primary care do not fit standard psychiatric labelling. An integrative model is described for understanding the relationships between stress, control and dependent behaviours with clinical utility for primary care. In this model, expectations disease occurs when expectations consistently disable rather than enable. This clinical diagnosis is characterized by five disorders of control which contribute to recurring episodes of loss of control. Disorders of control include, 1) unmet or excessive need for control, 2) impaired recognition of controllability, 3) misattribution of control, 4) control dissimulation and 5) fear of loss of control. Definitions and behavioural consequences for each control disorder are described. Loss of control is defined as a cascade of behaviours invoked to avoid or diminish chaotic or dissonant thinking through actions one would not deliberately choose (or not choose to the same degree) while feeling in control. Examples of loss of control include substance abuse, anger (rage or violence), binge behaviours (eating, shopping, gambling, sex, overwork), depression, panic and somatization. Loss of control paradoxically results in a transient sense of relief or shift of focus from the problem stimulus, but inevitably creates further problems over time. Expectations disease is determined not by the presence or absence of control disorders, but by the degree to which these problems exist--their chronicity, intensity and rigidity. For some, this disorder may be acute or intermittent, for others chronic; for some, a nuisance, for other, disabling. Short-term intervention for patients who present with clear distress, but unclear diagnosis is discussed. Advantages and disadvantages of the model are detailed. PMID- 8477890 TI - The diagnostic value of rectal examination. AB - The rectal examination is a much advocated procedure for assessing abdominal and urinary symptoms. A Medline literature search yielded only a few studies, not one of them in a general practice setting. The sensitivity of the rectal examination to rectal carcinoma and appendicitis is low, while it is high for prostate carcinoma. When reviewing the likelihood ratios of normal and abnormal findings of rectal examinations it was concluded that it may be a useful procedure in the case of abnormal findings in patients presenting rectal problems and in assessing men with prostate problems, although it does not seem useful in diagnosing appendicitis. However, since the diagnostic values in general practice and in referred populations may be different, there is a need for further prospective studies in settings of general medical practice. PMID- 8477891 TI - Withdrawing long-term diuretic treatment among elderly patients in general practice. AB - The aim of this study was to elaborate, implement and evaluate a strategy for discontinuation of long-term diuretic treatment in elderly patients in general practice. Thirty-three patients were enrolled for a supervised step-down and withdrawal of diuretics. After withdrawal, the patients were followed up for 6 months or until diuretic treatment was re-established. Withdrawal was successful according to the protocol in 18 cases. Diuretic withdrawal failed and the treatment was re-established in 15 cases, four of which were sudden cardiovascular events. Most withdrawal failures were identified by routine examinations through the follow-up programmes, thus they had few consequences for the patients. This demonstrates that careful follow-up is essential after diuretic withdrawal. Our findings support the view that a large proportion of elderly patients on diuretics may not need such treatment. PMID- 8477892 TI - Stuck with the patient--what would my colleague have done? A videorecorded consultation experiment with an actor simulating as the same patient for different doctors. AB - The aim of the experiment, in which four general practitioners met an actress who played a patient, was to explore how different doctors approach an identical patient problem. According to the patient role the actress had two reasons for encounter: (i) tachycardia and (ii) fear of HIV infection, which she had great difficulty in telling and presented only by indirect cues. The doctors knew they were meeting an actress, but the patient role description was unknown. Most of the time in each consultation was spent on tachycardia, the first presented symptom. None of the doctors paid real attention to the patient's signals of emotional distress and did not discover her fear of being HIV positive. Evaluation of the recordings and transcripts revealed some keys to understand why the doctors missed essential signals from the patient and felt stuck. It was difficult for the doctors to see their own role in blocking communication until the patient perspective was fully explored during the process of evaluation. PMID- 8477893 TI - Characteristics of registered clinic patients who have not visited their family physician for 3 years. AB - The objective of this study was to obtain and critically evaluate data on the health characteristics and the need for medical assistance in patients aged 40 years and over, from six urban and rural medical practices in northern Israel, who have not consulted their family physician for at least 3 years. A health questionnaire was completed by means of telephone calls and personal contacts, regarding 139 non-visitors (out of 1847 patients aged 40 and over). The health characteristics and prevalence of medical and social problems were compared to regular clinic attenders. Questionnaires of 101 non-attenders were completed for a response rate of 73% (101/139). The non-attendance rate was 7.5% (139/1847) and there was a low rate of morbidity. The majority (81%) were 40-59 years old and only 16% had had previous illnesses. Only 10% took medications regularly, most of them medical personnel. Twenty-eight of the non-attenders were employees of the regional health care system. Most of these individuals coped with chronic illnesses by consulting the regional hospital's outpatient clinics. Non-attenders could be characterized as less prone to health problems. Most of them seemed remarkably fit and were not suffering unduly as a result of their lack of medical attention. PMID- 8477894 TI - In search of excellence. Expanding the patient-centred clinical method: a three stage assessment. AB - Excellence in caring for the patient has been pursued in better technology and better management structures with multidisciplinary teams. Excellence is increasingly sought through taking the whole person seriously and in developing better ways of working with relationships. This paper traces the growth of ideas and their application in a university department of family medicine, toward a holistic and more patient-centred, three-stage clinical method. This three-stage assessment helps the patient and the physician to deal holistically with the problem. The biological, the psychological and the environmental systems as well as their interrelationships are considered as they impact on health and illness. This method of arriving at a 'best-fit' understanding of a person's problem, by the doctor and the patient together, helps to individualize the assessment and management. Excellence is more likely to be found when we care in an individualized way within a systems understanding. PMID- 8477895 TI - A review of the costs and effectiveness of assessing the elderly in general practice. AB - The 1990 contract for general practitioners made annual health checks for people aged 75 and over compulsory. We review the costs and effects of different approaches to the health check, focusing on the method advised in the 1990 contract. This involves an annual home-based functional assessment by a member of the primary health care team, known as a blanket assessment. Our review of published randomized controlled trials shows such assessments have few consistent benefits. Data on the costs of assessment are usually reported in summary form, with little or no information on which costs are included. In studies where average costs are given for assessments, because of salary and travel expenses, the costs are high. Several promising methods for reducing costs in assessment, and a method with potential to improve effectiveness, are currently outside the terms of the 1990 contract. These methods are described. Revision of the 1990 contract should incorporate the flexibility to encourage more cost-effective approaches to assessing the elderly such as a two-stage assessment or using volunteers. A monitoring group is needed to establish how health checks are being implemented. This group could co-ordinate and advise on standardized criteria for methods of costing and assessing effectiveness in assessment programmes. PMID- 8477896 TI - Self-report depression scales for elderly patients in primary care: a preliminary study. AB - In a primary care setting, the prevalence of depression in elderly patients was studied, and the reliability and validity of the geriatric depression scale (GDS) were assessed. In 141 consecutive elderly attenders (64-90) of four general practices, we estimated the point prevalence of depression with two self-rating depression scales. The results of the two scales were compared. Fourteen patients (12%) scored above cut-off on the Zung self-rating depression scale and 14 (12%) on the GDS. In 10 patients both scales indicated depression. The psychometric quality of both scales was adequate. The results of the investigation established prevalences found in other countries. The GDS may be a useful case-finding instrument aiding the general practitioner in the identification of depression in elderly patients. PMID- 8477897 TI - Smoking habits in early pregnancy related to age of smoking debut. AB - During 1 year, 187 general practitioners in western Norway recruited 530 daily smoking, pregnant women for a smoking cessation study. At the first medical check up in pregnancy each woman filled in a questionnaire. Women who had started smoking within 15 years of age reported more heavy smoking the last 3 months before pregnancy (P < 0.0001) and at the first check-up in pregnancy (P < 0.01) than those who had started smoking later. They also reported less reduction in smoking habits during earlier pregnancies (P < 0.0001) and more serious tobacco addiction judged by starting smoking early in the morning (P < 0.005). However, even those who had started smoking before 15 years of age reported a reduction of 30% in cigarette consumption during the first few weeks of the present pregnancy. In addition to increasing the antismoking efforts among pregnant women, health education among girls 12-15 years of age to prevent smoking initiation should be intensified. PMID- 8477898 TI - Counselling patients to make lifestyle changes: the role of physician self efficacy, training and beliefs about causes. AB - Three factors that might help explain the extent to which physicians counsel patients to quit smoking and lose weight were examined: counselling self efficacy, training in behaviour change and beliefs about causes of smoking and being overweight. More aggressive counselling was defined as counselling more patients per month and following up on counselling recommendations. Questionnaires were returned by 85 health maintenance organization physicians. As predicted, physicians with a stronger sense of counselling self-efficacy, and those who had received education in health behaviour change techniques were more aggressive counsellors. Motivational strategies were also explored. Physicians' beliefs about the causes of smoking and being overweight were related to the use of some types of strategies. Implications for increasing physician counselling patients to make behaviour changes are discussed. PMID- 8477899 TI - The nominal group technique: a research tool for general practice? AB - Qualitative methods are increasingly recognized as valuable, yet practitioners face difficult decisions in their choice of method and the process of analysis. The nominal group technique combines quantitative and qualitative data collection in a group setting, and avoids problems of group dynamics associated with other group methods such as brainstorming, Delphi and focus groups. Idea generation and problem solving are combined in a structured group process, which encourages and enhances the participation of group members. The stages involved in conducting a nominal group are described, and practical problems of its use in a health care setting are discussed with reference to a study of the priorities of care of diabetic patients, carers and health professionals. Some potential applications of the technique in audit and exploratory research are also outlined. PMID- 8477900 TI - Barriers to general practitioners caring for patients with HIV/AIDS. AB - This paper describes some of the barriers to caring for people with HIV and AIDS by general practitioners. It is based on a review of the literature and on interviews with individuals. The first section examines the reasons given by interviewees for their involvement in HIV and AIDS care. The next section discusses the relationship between primary and secondary care services in the care of patients with HIV and AIDS. One of the factors previously underexplored seems to be that of who 'owns' the patients. The final section looks at GPs' involvement in services for intravenous drug users with HIV and AIDS. It is concluded that there are still considerable barriers to GPs' involvement with patients with HIV and AIDS, in particular with drug users who have HIV or AIDS. It is likely that needs for continuing training in this area are not being met. PMID- 8477901 TI - The need for another look at the patient in general practice satisfaction surveys. AB - Although patient satisfaction research has looked at the aspects of care which patients are satisfied with and at which patients are satisfied with their care, few studies have looked at which patients are satisfied with which aspects of care. A retrospective analysis of data collected from 1599 patients attending 43 GPs was undertaken to examine the way that different patient characteristics influenced responses to a 31 item survey completed at the surgery after a consultation. Information on perceived distress [as measured by the Nottingham Health Profile (NHP)] was collected from patients prior to the consultation and further information about the patient and the consultation was recorded by the doctor after the consultation. Levels of satisfaction were high, with only seven of 31 items producing more than 5% of negative responses. These seven items covered whether the waiting time was too long, whether the doctor was relaxed, whether the doctor was in a hurry, whether there was anything else the patient would have liked to talk about had there been more time, whether the doctor had said or done anything to reduce the patient's worries, whether the doctor gave the feeling that the patient's opinions were important and whether there was anything about the consultation which disappointed the patient. Age, waiting time prior to the consultation, consultation length and positive scores on the six NHP dimensions of distress were all significantly associated with responses to one or more of these seven items. Patients experiencing pain and those with emotional distress were dissatisfied with different aspects of the consultation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477902 TI - Selections from current literature: using aspirin for primary or secondary prevention. AB - It seems evident that low doses (75 mg/day) of aspirin are adequate for attempts to prevent thrombotic occlusion of blood vessels. There are no data to suggest that different doses should be used based on whether primary or secondary prophylaxis is planned. However, even low doses of aspirin are associated with relatively small numbers of serious haemorrhagic complications. These complications are outweighed by the benefits of therapy in many examples of secondary prevention in high-risk groups that have already experienced an event or symptoms because of underlying vascular disease. Primary prophylaxis is a more controversial area. There is generally less to gain, and more to lose, when measures are applied to large numbers of asymptomatic people. Based on the available data, the conservative approach for aspirin use will be to reserve primary prophylaxis for those people with the highest estimated risk. PMID- 8477903 TI - Platelet adhesivity to subendothelium is influenced by polymorphonuclear leukocytes: studies with aspirin and salicylate. AB - Interactions between blood platelets and polymorphonuclear leukocytes (PMN) influence cell reactivity. We have examined the effects of inhibiting platelet and PMN cyclooxygenase and lipoxygenase pathways, by treatment with aspirin (ASA) and salicylate (SAL) on platelet-vessel wall interaction studied under flow conditions by means of an annular chamber perfusion system. We have also measured the levels of cyclooxygenase-derived metabolites during perfusion. Perfusates were prepared with untreated and ASA- or SAL-treated PMN or platelets. Our results demonstrated that blockage of the lipoxygenase pathway in PMN significantly increased platelet thrombus formation and favored the production of thromboxane B2 (TxB2) during perfusion, whereas inhibition of cyclooxygenase pathway in PMN had no effect either on platelet deposition or on TxB2 levels. In contrast, blockage of platelet cyclooxygenase, which caused almost total inhibition of TxB2, enhanced platelet adhesion and did not modify platelet thrombus formation. These results suggest that under dynamic conditions cooperative metabolic mechanisms between platelets and PMN directly influence platelet interaction with vascular subendothelium. PMID- 8477904 TI - Comparative plasma disposition and anticoagulant activities of racemic phenprocoumon and its metabolites in rats. AB - The anticoagulant phenprocoumon (PH) and its metabolites 6-hydroxy-, 7-hydroxy- and 4'hydroxy-phenprocoumon (6-OH-PH, 7-OH-PH and 4'-OH-PH, respectively) were separately administered intravenously as racemates to rats in order to measure the potential effects of the major metabolites of PH on coagulation. Plasma samples were assayed for total concentrations of the administered compounds and the corresponding prothrombin times; kinetic parameters and anticoagulant activities were estimated using a pharmacodynamic model based on the rate of synthesis of clotting factors. The relative potencies were in the order PH > 4' OH-PH > 6-OH-PH > 7-OH-PH the latter showing no activity. Patients on PH therapy showed lower plasma concentrations of metabolites than of PH; in humans the metabolites of PH will not contribute significantly to the overall anticoagulant activity of the drug. PMID- 8477905 TI - Which coagulation factors interfere with the one-stage prothrombin time? AB - Coagulation factors that interfere with the one-stage prothrombin time (PT) were investigated. PT responded with identical activities (adequately) against coagulation factors VII or X, only half as expected against factor IX, less than expected and nonlinearly against factor II. In multiple coagulation factor deficiencies PT did not differ from factor VII, which was the most reduced coagulation factor in warfarin therapy or liver disease. PT may also be influenced by factor VII at high activities. PMID- 8477906 TI - Development of a rapid and sensitive chromogenic heparin assay for clinical use. AB - A new sensitive chromogenic heparin assay is developed, which is well suited for clinical use. For the assay two reaction mixtures are required which can be lyophilized and reconstituted on the day of use. These reagents are stable during at least 6 h. Only two time-dependent pipetting steps are necessary. Any compound that inactivates thrombin, or can potentiate thrombin inactivation by an inhibitor, can be measured with this assay, including standard heparin, low molecular weight heparins, hirudin, alpha-NAPAP, pentosan polysulphate and dermatan sulphate. It is shown that heparin can be measured accurately in whole blood and in plasma. By addition of dextran sulphate to one of the reagents a platelet factor 4-insensitive assay is developed, so heparin can be measured even in blood that is partially activated and thus contains platelet factor 4 which neutralizes heparin. PMID- 8477907 TI - Fibrinolytic imbalance in essential thrombocythemia: role of platelets. AB - Thrombotic and hemorrhagic complications are frequent in patients with essential thrombocythemia (ET), a myeloproliferative syndrome with an increased number of circulating platelets. Since platelets are a physiological reservoir for the plasminogen activator inhibitor (PAI-1) contained in plasma, we evaluated plasma and platelet tissue plasminogen activator (tPA) and PAI-1 in 20 ET patients with and without thrombotic complications and in 13 control subjects. In ET patients with thrombotic complications there was a significantly greater platelet PAI-1 functional activity than in ET patients without thrombotic complications and in the control group (p < 0.05 and p < 0.025, respectively). Moreover, platelet tPA activity was significantly low in all ET patients (p < 0.001). This fibrinolytic imbalance (increased plasminogen inhibitor and lowered activator) might be a critical cofactor in the thrombotic complications in ET patients. PMID- 8477908 TI - Prothrombin fragment 1 + 2 and thrombin-antithrombin complex measurements indicate continuous and progressive intraoperative thrombin generation in liver transplantation. AB - Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complex (TAT) have been measured in the different surgical phases in 40 patients undergoing 43 orthotopic liver transplantations (OLT), in order to study thrombin generation throughout the surgical procedure. F1 + 2 and TAT progressively rose from preoperative values (1.47 +/- 0.92 nmol/l and 22.41 +/- 19.15 ng/ml, respectively) to the end of anhepatic phase (5.97 +/- 2.20 nmol/l, 64.24 +/- 11.30 ng/ml), whereas changes in circulating antithrombin III (ATIII) were negligible in this period. Thrombin generation continued to slightly but significantly increase immediately after liver graft reperfusion (F1 + 2 6.87 +/- 1.65 nmol/l, TAT 89.32 +/- 7.54 ng/ml), and ATIII levels decreased from 70.61 +/- 12.28 to 57.16 +/- 9.57%. Higher preoperative values of F1 + 2 were associated with larger requirements of both packed red blood cells and fresh frozen plasma (FFP) in the host liver explantation phase, whereas the lowest basal levels of ATIII were related to a higher plasma expense in the whole OLT procedure. The activation of circulating prothrombin begins early in OLT, and adequate FFP infusion is capable of maintaining appropriate circulating thrombin-inhibitory activity. PMID- 8477909 TI - Endothelium releases more von Willebrand factor and tissue-type plasminogen activator upon venous occlusion in patients with liver cirrhosis than in normals. AB - Venous occlusion was used in 8 patients with liver cirrhosis and in 10 normals to investigate the pathomechanism of long-term elevation of plasma von Willebrand factor antigen (vWFAg) in liver cirrhosis. The following parameters were determined at baseline, and immediately, 60 min and 24 h after 10 min venous occlusion: vWFAg, ristocetin cofactor (RiCoF), in vitro platelet retention (Adeplat T), and tissue-type plasminogen activator (t-PA). Every baseline value in the liver cirrhosis group was significantly higher than in the controls. In both groups the 10-min values were significantly higher than their corresponding baseline results. Hence, comparing the two groups, in liver cirrhosis a significantly higher release of vWFAg and t-PA could be observed. These findings suggest on the one hand that the increased release contributes substantially to the sustained elevation of plasma vWF level in liver cirrhosis. On the other hand, the results indicate that not only the vascular surface of the diseased liver but most probably the total endothelium plays an important role in this phenomenon. PMID- 8477910 TI - Cardiac surgery with extracorporeal circulation in severe factor VII deficiency. AB - We describe here successful open heart surgery with extracorporeal circulation and haemodilution in a child with severe congenital factor VII deficiency. Substitution therapy was realized with factor VII concentrate (SD proconvertin concentrate, Bio-Transfusion). This is the first report case of successful cardiac surgery in severe congenital factor VII deficiency. PMID- 8477911 TI - An acquired cryoglobulinemia which inhibits fibrin polymerization in a patient with IgG kappa myeloma. AB - A 58-year-old man with multiple myeloma and paraproteinemia (IgG kappa) acquired cryoglobulinemia 2 years after the initial diagnosis of the disease. This cryoglobulin interfered specifically with fibrin aggregation. The patient's fibrinogen was functionally normal; however, clotting times (thrombin clotting time, reptilase clotting time) were prolonged in the untreated plasma and in the supernatant after removal of the cryoglobulins. Untreated patient's serum, and even more pronounced, the cryoprecipitate inhibited the association of fibrin monomers obtained from healthy controls. The inhibitory activity on fibrin aggregation diminished upon treatment-induced reduction of plasma protein levels. PMID- 8477912 TI - Effects of aspirin on embolization in an arterial model of laser-induced thrombus formation. AB - This model of arterial thrombosis induced by laser was used to evaluate the effect of aspirin (Aspegic) on embolization. A partial occlusion was induced in small mesenteric arterioles (diameter 35-40 microns) with an Argon Laser. The laser induced the formation of a vessel wall lesion with damage of endothelial cells. Thrombus formed within seconds after the laser lesion and grew rapidly. Embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenomena. The duration of embolization was 6.50 +/- 0.84 min in the control group. Then the thrombus became stable and partially obstructed the vessel lumen. The administration of aspirin at three doses (50, 100, 200 mg/kg) by intramuscular injection, 15 min before the laser injury, induced three different phenomena: (1) an increase of the number of laser injuries required for the thrombus formation; (2) a dose-dependent decrease in the duration of embolization, and (3) a dose-dependent decrease in the number of emboli. The highest dose injected induced the strongest reduction in the duration of embolization and the number of emboli. PMID- 8477913 TI - Toxicity threshold of quinine hydrochloride following low-level repeated dosing in healthy volunteers. AB - Following a double-blind, four-way crossover design, 32 healthy volunteers (20 males and 12 females) each consumed lactose placebo, or 80, 120 or 160 mg quinine HCl daily for 21 days. Before dosing and at regular intervals during dosing, blood and urine samples were collected and analysed for quinine HCl. Electrocardiography, heart rate, blood pressure, audiometry, peripheral field, funduscopy, colour vision, visual acuity, electronystagmography (ENG) and test for optokinetic nystagmus were all evaluated before dosing and at selected times during dosing. The results showed that daily consumption of up to 80 mg quinine HCl did not significantly alter physiological, ophthalmic or audiometric responses. ENG determination showed that 12.5% of volunteers given lactose placebo or 80 mg quinine HCl exhibited at least one transitory period of ocular motor oscillations. This phenomenon was observed in 18.8% (P < 0.05) of volunteers with a daily intake of 120 mg quinine HCl or more. However, there was not a significant dose-related correlation between nystagmus and daily intake of quinine HCl. Five volunteers consuming lactose placebo displayed an aberrant ocular flutter that decreased significantly (P < 0.05) as the daily intake of quinine HCl increased. One volunteer showed a change in perception of red/green colour vision after taking 160 mg quinine HCl for 21 days. This study demonstrated that the no-untoward-effect level of quinine HCl is at least 80 mg/day. PMID- 8477914 TI - Thyroid function and other clinical chemistry parameters in subjects eating iodine-enriched eggs. AB - Iodine-enriched (IE) eggs are produced by chickens fed a diet containing kelp. These eggs, which contain an average of 711 micrograms iodine/egg, have been reported to reduce plasma cholesterol in humans and laboratory animals. A modified form of these eggs is under consideration for marketing in the United States. 104 hyperlipidaemic subjects were placed on a low-fat diet for 12 wk. Between wk 4 and 12, approximately half of the subjects were randomized to a dietary control group (n = 53) or a group who ingested one IE egg/day in addition to this diet (n = 51). Some subjects in both groups continued in the study for an additional 4-8 wk. No significant adverse clinical effects were observed or reported, with the exception of one subject who reported an allergic-like reaction soon after beginning egg ingestion. All clinical chemistry values remained within normal limits, and comparisons between the egg group and controls were not significant. Three subjects (two in the egg group and one in the control group) had elevated thyroid stimulating hormone levels during the experimental period. All thyroid function tests remained within normal limits in the remaining subjects. Thus, ingestion of one IE egg of the type used in our study appears to be relatively safe and devoid of clinically significant, short-term adverse effects in healthy individuals. PMID- 8477915 TI - Tissue distribution and excretion of 14C-labelled cinnamic aldehyde following single and multiple oral administration in male Fischer 344 rats. AB - 14C-labelled cinnamic aldehyde (CNMA) was given as a single oral dose, or 24 hr after multiple oral administration of non-radioactive CNMA for 7 days at 24-hr intervals, to male Fischer 344 rats at dose levels of 5, 50 or 500 mg/kg body weight. Residues of radioactive CNMA were measured. After the single dose radioactivity was distributed primarily in the gastro-intestinal tract, the kidneys and the liver of the rats. The radiolabel was excreted mainly in the urine, and at 24 hr 85.1, 84.2 and 81.2% of the administered radiolabel was recovered in the urine at the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel at 24 hr for the 5, 50 and 500 mg/kg doses was 5.1, 4.0 and 3.2% of the administered dose, respectively. At all dose levels, a small amount of the dose was distributed to the fat and was easily measured in animals killed 3 days after dosing at the 50 or 500 mg/kg dose levels. Following multiple oral administration, similar tissue distribution and excretion patterns of radiolabel were found at the three dose levels. After 24 hr the administered radiolabel was distributed mainly to the fat, liver and gastro-intestinal tract. At 24 hr, recoveries of the radiolabel in the urine were 80.4, 80.6 and 81.9% of the dose for the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel after multiple dosing at 24 hr accounted for 6.3, 6.9 and 4.5% of the administered radioactivity at the 5, 50 and 500 mg/kg dose levels, respectively. The major metabolic pathway of CNMA for all single and the 5 and 50 mg/kg multiple dose levels in this species of rat was found to be degradation to benzoic acid through beta-oxidation and excretion in the urine mainly as hippuric acid, with much smaller amounts of benzoic and cinnamic acids. At the multiple dose level of 500 mg/kg, benzoic acid was the major urinary metabolite, indicating that in the Fischer 344 male rat at this relatively high oral dose level the detoxification of CNMA proceeds differently and an alternative metabolic pathway is proposed. PMID- 8477916 TI - Lipid content and composition of coffee brews prepared by different methods. AB - The lipid content and composition of boiled, filtered, dripped, Turkish and espresso coffees prepared from roasted beans of Coffea arabica and Coffea robusta, and of coffees prepared from different brands of instant coffee were examined. The lipid content varied with the method of preparation. While coffee brews filtered through filter paper contained less than 7 mg lipids, those prepared by boiling without filtering and espresso coffee reached 60-160 mg lipids/150-ml cup. Coffee brew filtered through a metal screener contained 50 mg lipids/150-ml cup. Although the lipid content varied, the method of preparation of the brew and filtration had no important influence on the lipid composition. During paper filtration lipids remained mainly in spent coffee grounds, and the brew and filter paper retained only 0.4 and 9.4%, respectively, of the total lipids recovered. However, the lipids in the brew, filter paper and spent coffee grounds had the same profile, indicating that there was no preferential retention of a particular lipid component in filter paper. Triglycerides and diterpene alcohol esters were the major lipid classes in coffee brewed from ground coffee beans, and ranged from 86.6 to 92.9 and 6.5 to 12.5% of total lipids, respectively. For coffee brews made from instant coffee, the levels of these two lipid classes were 96.4-98.5 and 1.6-3.6%, respectively. The lipid contents of both regular and decaffeinated instant coffees varied slightly from one brand to the other, and ranged from 1.8 to 6.6 mg/150-ml cup. PMID- 8477917 TI - Haemotoxic effect of phenylurea herbicides in rats: role of haemoglobin-adduct formation in splenic toxicity. AB - Three substituted phenylurea herbicides were used for the study of the haemotoxic effects on rats of chronic exposure to these compounds. Female Sprague-Dawley rats were given monuron, diuron or fenuron (250-1000 mg/kg diet) for 14 months. The final body weights were similar to those of controls. No treatment-related effects on organ weights were observed at autopsy, except for a dose-related increase in spleen weights in rats treated with monuron or diuron, but not in those treated with fenuron. The proportion of haemoglobin in the form of methaemoglobin increased in the dosed group and resulted in a secondary anaemia with changes in the morphology of erythrocytes. Haemoglobin adducts of aromatic amines released from the herbicides were present at dose-related levels in rats treated with monuron or diuron. Compound-related lesions were observed histologically in treated rats, with increased pigmentation (haemosiderin) in the spleen, reflecting the response to the haemolytic anaemia and methaemoglobinaemia induced by the herbicides. Pigment deposition consisting of golden brown granules in the cytoplasm of the tubular epithelium in the kidney and in the Kupffer cells in the liver were observed only in rats treated with monuron. The haemotoxic effects that were observed may indicate that the formation of adducts between haemoglobin and the parent aromatic amines released metabolically from these herbicides has a role in the splenic toxicity of these compounds. PMID- 8477918 TI - Toxicological studies on debitterized Neem oil (Azadirachta indica). AB - Azadirachta indica, popularly known as 'Neem' in India, is widely grown all over the tropics. The seed contains 45% oil and is a minor oil of considerable potential. Neem oil is bitter and inedible. Recently, a method has been developed to completely remove the bitter and odoriferous principles and leave a bitterless, odourless and colourless oil. The nutritional and chemical evaluation of debitterized neem oil (NO) was reported earlier (C. Rukmini, Food Chemistry 1987, 26, 119). We report here a three-generation study, carried out according to WHO/FDA protocol in groups of 15 male and 15 female rats fed a diet containing 10% NO or groundnut oil (GNO). Reproductive toxicology was monitored for three generations. The results obtained in both the matings in all the three generations did not show any adverse effects on the reproductive parameters studied in rats fed NO and were similar to those observed in rats fed GNO. The mean organ weights and the histopathological evaluation of all the organs were similar to those of the control (GNO-fed) rats. A mutagenicity test of NO was also found to be negative in Ames test as reported earlier (K. Polasa and C. Rukmini, Food and Chemical Toxicology 1987, 25, 763). These studies indicate that NO devoid of all the bitter and odoriferous principles, may be recommended as safe for consumption by humans. PMID- 8477919 TI - Sulphur dioxide, acid aerosols and particulates. PMID- 8477920 TI - [The psychiatric day clinic--a review of experience to date and our results]. AB - Psychiatric day hospitals are a relatively young therapeutic facility insufficiently known to many psychiatrists. This accounts for the application potential of day treatment not being adequately recognised and utilised despite its many advantages (efficacy, flexibility, versatility). Treatment at a day hospital is not a (more or less) acceptable alternative to hospitalisation but has a specific contribution of its own to make in certain situations. Although the scientific standard of the literature published on day hospitals is relatively good, many questions on theoretical and practical aspects remain unanswered. The aim of this paper is to show the opportunities and limitations of the psychiatric day hospital with reference to a survey of the existing literature and to our own experience. PMID- 8477921 TI - [The determination of cerebral speech dominance with the intracarotid amobarbital test]. AB - In neuropsychological diagnostics of lateralisation of cognitive functions, the intracarotid amobarbital procedure (IAP) is a well established method for the determination of cerebral language dominance. In this review, different frameworks of classification of dominance patterns are discussed, ranging from the simple left/right/bilateral-dominance framework to a quantitative analysis according to a computed lateralisation index. Evidence from IAP studies concerning the cerebral organisation of linguistic subfunctions like naming and reading are discussed. A critical evaluation of rivalling approaches like electrical stimulation mapping or visual hemifield studies suggests that these methods mainly yield results complementary to IAP data and hence should not be taken as substitutes of that procedure. PMID- 8477922 TI - [Disorders of eye movements in schizophrenia--a critical review and future perspectives]. AB - Disorders of smooth pursuit eye movements and saccadic eye movements have been reported frequently in schizophrenics. Probably 50% of the schizophrenic probands and of their unaffected relatives perform abnormal smooth pursuit movements. These deficiencies have been regarded as a possible genetic trait marker for schizophrenic vulnerability. Saccadic eye movements have been investigated less intesively. The most prominent pathological feature is a lack of precision of reflexive saccades in case of schizophrenic probands. Although a large body of research has been conducted, the multitude of the results of eye movement disorders in schizophrenics and also technical and methodological problems impair the significance of these findings. In this review, the most important results are critically elaborated and research perspectives are pointed out. A valid identification of eye movement abnormalities is necessary. PMID- 8477923 TI - [A case of idiopathic hyperaldosteronism diagnosed by adrenal imaging]. AB - We report a case of idiopathic hyperaldosteronism (IHA) which was differentiated from an aldosterone producing adenoma by the adrenal imaging techniques with computed tomography (CT) and scintigraphy. In this patient, the high basal aldosterone level with the suppressed plasma renin activity typically indicated the diagnosis of primary aldosteronism. However, the differentiation from an aldosterone producing adenoma by responses of plasma aldosterone levels to upright posture, captopril or adrenocorticotropic hormone (ACTH) administration was not definitive. Abdominal CT revealed bilateral adrenal swelling. Adrenal scintillation scanning with 131I-iodocholesterol showed bilateral uptake even after the administration of dexamethasone. Blood sampling from the right adrenal vein was unsuccessful. Blood pressure and serum potassium levels remained unchanged during dexamethasone administration (2 mg/day) over ten days. After the administration of spironolactone and nisoldipine blood pressure and serum potassium levels were normalized. Adrenal imaging is considered to be very useful for the diagnosis of IHA. PMID- 8477924 TI - [Etiology of diabetic microangiopathy]. PMID- 8477925 TI - [Two cases of huge hepatic hemangioma]. AB - We have experienced two cases of huge hepatic hemangioma. Case 1 was a 51-year old man complaining of abdominal fullness and was shown low density area in the right hepatic lobe by abdominal computed tomography. He was treated with segmentectomy of the right hepatic lobe. The resected specimen was histologically diagnosed as cavernous hemangioma. Case 2 was a 61-year-old man who showed no symptom and was shown 10 x 6.5 cm hemangioma by abdominal ultrasonography. He have been untreated. For 10 years, 29 cases of huge hepatic hemangioma, including our two cases have been reported in Japan. The female to male ratio is 5:1. The incidence of huge hepatic hemangioma was frequent in the fifth and sixth decades of life. The majority of patients complained of palpable abdominal mass and abdominal pain. The dominant site of huge hepatic hemangioma was the anatomical right hepatic lobe. PMID- 8477926 TI - Safeguarding quality in managed competition. PMID- 8477927 TI - Challenges for managed competition from chronic illness. PMID- 8477928 TI - Doctors, dollars, and determination: making physician work-force policy. AB - Because managed care is likely to feature prominently in a reformed health care system, policymakers need to examine the impact managed care will have on medical practice, physician supply, and access to primary care providers. Goals for work force reform should focus on five areas: (1) training physicians in the generalist disciplines of family practice, general internal medicine, and general pediatrics; (2) shaping the physician work force to reflect the nation's ethnic diversity; (3) distributing physicians in a geographically equitable way; (4) maintaining the current physician-to-population ratio rather than letting it continue to grow; and (5) establishing supply needs for nurse practitioners, primary care physician assistants, and certified nurse midwives. PMID- 8477929 TI - An iconoclastic view of health cost containment. AB - Calls for medical care cost containment are all around us. Although the evidence that costs are too high is strong, the evidence that they are rising too quickly is much weaker. The principal cause of increasing costs appears to be the increased capabilities of medicine; the scant evidence available suggests that to date the public has wanted to pay for most of these capabilities. Effective global budgets would address the rising opportunity costs of health care. However, they would threaten ongoing innovation and probably would increase distortions from pricing errors. PMID- 8477930 TI - Reorganizing the financial flows in American health care. AB - The essays in this volume concentrate heavily on "managed competition," which is merely a particular form of controlling the flow of funds from an insurance pool to the providers of health care. By contrast, this essay emphasizes the funneling of money into the insurance fund. It is argued inter alia that American business has been a quite unreliable partner in the financing of American health care and also a major cost driver. A reformed health system should reduce the role of business to the mere collection of premiums at the nexus of payroll. PMID- 8477931 TI - The need for a national global budget. PMID- 8477932 TI - Managed competition: little cost containment without budget limits. PMID- 8477933 TI - Can managed competition solve the problems of market failure? PMID- 8477934 TI - Potential public expenditures under managed competition. AB - This DataWatch estimates the public cost of providing universal coverage under a managed competition model. First, a uniform benefit package is specified; next, the lowest-cost premium for this coverage is estimated, based on average costs in a well-managed health maintenance organization (HMO). Based on these estimates, the cost of premium subsidies and tax revenue effects are determined. It is estimated that if coverage is extended to currently uninsured persons using these estimates and assumptions, spending for these persons will increase 73.9 percent over current levels. The authors estimate a net increase of $47.9 billion in 1993 health spending under a managed competition program with low patient cost sharing. This includes savings of $4.5 billion from wider use of managed care and $11.2 billion in administrative cost savings. PMID- 8477935 TI - The history and principles of managed competition. AB - Managed competition in health care is an idea that has evolved over two decades of research and refinement. It is defined as a purchasing strategy to obtain maximum value for consumers and employers, using rules for competition derived from microeconomic principles. A sponsor (either an employer, a governmental entity, or a purchasing cooperative), acting on behalf of a large group of subscribers, structures and adjusts the market to overcome attempts by insurers to avoid price competition. The sponsor establishes rules of equity, selects participating plans, manages the enrollment process, creates price-elastic demand, and manages risk selection. Managed competition is based on comprehensive care organizations that integrate financing and delivery. Prospects for its success are based on the success and potential of a number of high-quality, cost effective, organized systems of care already in existence, especially prepaid group practices. As it is outlined here, managed competition as a means to reform the U.S. health care system is compatible with Americans' preferences for pluralism, individual choice and responsibility, and universal coverage. PMID- 8477936 TI - Managed competition estimates for policy making. PMID- 8477937 TI - Potential impact of managed care on national health spending. AB - Illustrative estimates suggest that if all acute health care services were delivered through staff- or group-model health maintenance organizations (HMOs), national health spending might be almost 10 percent lower. If the delivery of all such services (except those now provided by staff- or group-model HMOs) were subject to utilization review arrangements incorporating precertification and concurrent review of inpatient care, spending might be 1 percent lower. The estimates assume no changes in the health care system apart from expansion of these two forms of managed care to cover all insured persons. They also assume that moving to universal managed care would produce a one-time drop in the level of national health spending with no subsequent effect on spending growth. PMID- 8477938 TI - Physician satisfaction under managed care. AB - Data from a survey of young physicians have been analyzed to study the relationship between practicing medicine under managed care and the levels of perceived professional autonomy, practice satisfaction, and career satisfaction. Although practicing under managed care is associated with lower levels of perceived autonomy in patient selection and time allocation, it is associated with higher levels of perceived autonomy in use of hospital care, tests, and procedures. Specialists associated with managed care perceive more autonomy than generalists. Analyses of physicians' satisfaction with their practices and careers show that practicing under managed care is not uniformly associated with lower levels of satisfaction. Overall, managed care does not seem to have had the deleterious impact on medical practice that was forecast for it. PMID- 8477939 TI - Twenty-four-hour coverage and workers' compensation insurance. AB - Workers' compensation insurance provides cash benefits and health care for workers who are injured on the job. This DataWatch considers the costs and benefits of combining the health insurance component of workers' compensation with universal health insurance, creating a twenty-four-hour coverage plan. The paper documents a large potential savings from twenty-four-hour coverage: Workers' compensation medical charges are about twice as high as those for comparable off-work injuries. This disparity seems to result from price discrimination and lack of cost controls in workers' compensation. Twenty-four hour coverage, however, may be difficult to implement. PMID- 8477940 TI - Gaps in employer coverage: lack of supply or lack of demand? AB - According to data from the May 1988 Current Population Survey, 18 percent of workers are in firms that do not offer health insurance. The question explored here is whether the absence of insurance in these firms is related to lack of supply (that is, a failure of the firm to offer the benefit because the price it faces is too high or the benefit too low) or lack of demand (that is, employees in these firms would not purchase the insurance even if it were offered). Characteristics hypothesized to affect the supply of insurance by firms (size, rate of turnover, and union status) are found to distinguish whether or not firms offer insurance. The data show near-universal acceptance of group insurance among employees offered the opportunity to participate. Both of these factors suggest a failure of supply. However, employees in firms that do not offer insurance are young, low-wage earners who work part time. These are also characteristics of workers who do not purchase group insurance even when it is offered, suggesting that many of the workers who are not offered group insurance would not participate in a plan even if the supply failure were corrected. These findings have implications for the effectiveness of voluntary strategies to improve access, but they also raise concern over the fairness to workers of mandates requiring that they purchase coverage. PMID- 8477941 TI - Health care financing reform in Russia and Ukraine. PMID- 8477942 TI - Who should govern the purchasing cooperative? PMID- 8477943 TI - Design of health insurance purchasing cooperatives. PMID- 8477944 TI - A payment method for health insurance purchasing cooperatives. PMID- 8477945 TI - A bridge to compromise: competition under a budget. AB - A new approach to universal health insurance combining managed competition and global budgets promises to break the impasse blocking comprehensive health reform. The central innovation is the development of regional health insurance purchasing cooperatives (HIPCs) as managers and reorganizers of the market and platforms for global budgets. Financing would be based on community-rated premiums, with obligations to employers capped as a percentage of payroll and to individuals as a percentage of family income. Budgets would cap the mandated core of spending and set a target for out-of-pocket expenditures. PMID- 8477946 TI - Informing and protecting consumers under managed competition. PMID- 8477947 TI - Where should the buck stop: federal and state responsibilities in health care financing reform. PMID- 8477948 TI - Benefit design choices under managed competition. PMID- 8477949 TI - Effects of amylin on the release of insulin and glucagon from the perfused rat pancreas. AB - Amylin is a normal secretory protein of the pancreatic beta-cells as well as a major constituent of the islet amyloid deposits in patients with non-insulin dependent diabetes mellitus. We studied the effects of amylin on the release of insulin and glucagon from the isolated perfused rat pancreas. Rat amylin was dissolved in basal perfusates to a final concentration of 100 nM. Amylin did not alter glucose-stimulated secretion of insulin but significantly inhibited arginine-stimulated secretion of insulin (control: 20.9 +/- 1.4 pmol/min; amylin group: 14.8 +/- 1.6 pmol/min, p < 0.05). Amylin did not alter the release of glucagon from the perfused rat pancreas in response to 16.7 mM glucose and 10 mM arginine. These findings suggest that amylin may modulate the secretion of insulin from pancreatic beta-cells. PMID- 8477950 TI - Effect of epinephrine on 86Rb efflux, 45Ca outflow and insulin release from pancreatic islets perifused in the presence of propranolol. AB - Pancreatic islets prelabelled with either 86Rb or 45Ca were perifused in the presence of propranolol (0.1 microM) and, when required, exposed to epinephrine (0.1 microM). In the absence of D-glucose, epinephrine failed to cause any obvious change in either 86Rb or 45Ca outflow. In the presence of 16.7 mM D glucose, however, epinephrine lowered both 86Rb and 45Ca outflow, this coinciding with suppression of insulin release. Epinephrine also suppressed the increment in 86Rb outflow evoked by a rise in glucose-concentration from 8.3 to 16.7 mM. Epinephrine did not abolish the early fall in 45Ca efflux evoked by the administration of D-glucose (16.7 mM) to islets previously deprived of the hexose but, within the same experiments, impaired the secondary rise in effluent radioactivity. Likewise, epinephrine prevented the increase in 45Ca outflow provoked by a rise in hexose concentration from 8.3 to 16.7 mM. These findings are compatible with the recent proposal that epinephrine interferes with the entry of Ca2+ into the B-cell, as mediated by voltage-sensitive Ca2+ channels, but do not rule out a multifactorial coupling between the occupancy of alpha 2 adrenergic receptors and the eventual inhibition of insulin release. PMID- 8477951 TI - The concept of metabolic clearance rate in endocrinology. A case study of growth hormone in different lines of meat-type chickens. AB - Disappearance of growth hormone from blood (plasma) was studied in young broiler chickens in two experiments: a) following single injection of GH (50 micrograms or 250 micrograms/kg) to anesthetized chicks; b) injection of GH (50 micrograms/kg) (under anesthesia) to two lines of broilers selected for either rapid growth or feed efficiency. Clearance of GH never followed a single negative exponential curve. Characterization of the disappearance by a single metabolic clearance rate and half-life time were found to be inaccurate and inappropriate on methodological grounds. High doses of hormone might disturb receptor or catabolism equilibria and result in aberrant values of MCR which could probably be because of the very dynamic nature of the GH clearance system, which appeared to be influenced by dose, line (or genetics of the animal) and by some indices of clearance. Therefore, physiological significance of such data must be interpreted carefully. PMID- 8477952 TI - Thyroid hormone restores atrial stretch-induced secretion of atrial natriuretic peptide in hypophysectomized rats. AB - Acute blood volume expansion caused a rapid and profound release of atrial natriuretic peptides (ANP) from cardiac atria. The stimulated release of ANP was markedly blunted (more than 50%) in hypophysectomized rats (8 days after surgery). Daily subcutaneous injections of thyroxine (30 micrograms/kg) to hypophysectomized rats for 7 days, completely restored acute volume expansion induced release of ANP. Our data suggest that thyroid hormone is required for ANP secretion in response to acute volume expansion. PMID- 8477953 TI - Effect of ascorbic acid administration on B and E apoproteins in rats fed a cholesterol enriched diet. AB - The effect of ascorbic acid on cholesterol metabolism is very well documented; it is ascribed to the activation of this vitamin on cholesterol 7 alpha-hydroxylase (EC 1.14) that activates the catabolism of cholesterol. In this paper we have studied the effect of the administration of ascorbic acid on B and E apoproteins of rats fed a diet enriched with 1.5% of cholesterol. The results obtained show that ascorbic acid is able to affect cholesterol metabolism by modifying the serum levels of apo B in total serum and in lipoprotein classes of density less than 1.050 g/ml. Moreover the ascorbic acid treatment reduced the amount of cholesterol and triglycerides in all lipoprotein classes examined. No significant change of total serum apo E was observed following ascorbic acid administration. PMID- 8477954 TI - Mononuclear leukocytes from obese patients with type II diabetes have reduced activity of hexokinase, 6-phosphofructokinase and glucose-6-phosphate dehydrogenase. AB - In the present study we measured the activity of some cytosolic enzymes involved in intracellular glucose metabolism in mononuclear leukocytes from 77 obese subjects of which 39 were nondiabetic and 38 had newly-diagnosed untreated type II diabetes mellitus. 28 subjects (19 nondiabetic and 18 diabetic) had also a study of insulin binding to monocytes. 35 subjects (14 nondiabetic, 21 diabetic) underwent an insulin tolerance test for the evaluation of in vivo insulin action. Mononuclear leukocytes from diabetic obese patients showed significantly lower activities of hexokinase (HK), 6-phosphofructokinase (PFK) and glucose-6 phosphate dehydrogenase (G6PDH), while pyruvate kinase (PK) and 6 phosphogluconate dehydrogenase (6PGDH) activities were similar in the two groups. In the whole population HK and G6PDH activities inversely correlated with fasting and 2-h OGTT plasma glucose levels. Neither plasma insulin levels nor maximal specific insulin binding to monocytes were significantly correlated with any of the enzyme activities measured. Conversely, the parameter of insulin action generated by insulin tolerance test significantly correlated with HK, G6PDH and 6PGDH. These results indicate that in obese subjects the presence of diabetes is associated with a reduced activity of some enzymes of glucose metabolism in mononuclear leukocytes. This multiple enzymatic defect is correlated with the impairment of in vivo insulin action. PMID- 8477955 TI - In vivo and in vitro effects of glucocorticoids on glucose transport in human polymorphonuclear leukocytes. AB - In order to study whether or not exogenous and/or endogenous glucocorticoids affect the glucose transport rate in human cells, we examined the transport rate of a non-metabolizable hexose analogue, 3-O-methyl-D-glucose, in polymorphonuclear leukocytes from patients with hypercortisolism. The mean glucose transport rate was prominently decreased in 5 patients with Cushing's syndrome compared with 29 healthy controls (5.4 +/- 1.8 vs 10.4 +/- 2.5 fl/cell.sec, mean +/- SD, p < 0.001) and the transport rate returned to normal range after adenoma resection in 2 of them. In 10 patients with nephrotic syndrome treated with prednisolone, a significant negative correlation was found between transport rates and daily prednisolone doses. When prednisolone of 40 mg/day was administered to a diabetic patient and the dose was gradually reduced, glucose transport rate was transiently decreased during the initial period. In an in vitro study, a synthetic glucocorticoid, dexamethasone, directly inhibited glucose transport rate in those cells in time- and concentration-dependent manners by mainly reducing Vmax. These results suggest that either exogenous or endogenous hypercortisolism in humans is associated with a decrease in glucose transport rate in polymorphonuclear leukocytes, and that the direct effect of glucocorticoids accounts at least in part for the decreased glucose transport rates found in those cells. PMID- 8477957 TI - Long-term impairment of adrenal function after unilateral adrenalectomy. PMID- 8477956 TI - Evidence for increased sensitivity of fuel mobilization to growth hormone during short-term fasting in humans. AB - Since growth hormone (GH) secretion is increased with fasting, the study was designed to assess the effects of short-term fasting on both basal and GH stimulated substrate metabolism. Seven normal healthy subjects were studied following a 12 h and a 36 h fast ("fasting"), for 2 h in the basal state and for a further 4 1/2 h after an i.v. bolus injection of 140 micrograms GH. As expected fasting induced decrements in circulating concentrations of insulin and C-peptide (p < 0.05) and increments in glucagon concentrations (p < 0.05), together with a slight increase in serum GH concentrations (p > 0.05). Furthermore plasma glucose values, isotopically determined turnover rate for glucose and forearm uptake of glucose were all substantially reduced during fasting (p < 0.05). By contrast circulating levels of all measured lipid intermediates (free fatty acids [FFA], 3 hydroxybutyrate [3-OHB] and glycerol) and the forearm uptake of 3-OHB were clearly elevated during the fast (p < 0.05). Serum GH rose to a peak of 17.0 +/- 2.7 within 10 min of injection in both situations. Blood concentrations of hormones and parameters of glucose metabolism remained unaffected. After administration of GH circulating levels of lipid intermediates increased markedly in both situations, the increase being most pronounced in the fasting state (p < 0.05). During fasting peak levels of 1775 +/- 150 mumol/l and 1780 +/- 360 mumol/l of FFA and 3-OHB were observed compared to postabsorptive peaks of 980 +/ 100 and 230 +/- 90 mumol/l respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477958 TI - Intra-uterine fetal death due to pre-eclampsia which was misdiagnosed to be complicating with hepatitis. PMID- 8477959 TI - Histological evaluation of the intrahepatic biliary tree in intrahepatic cholesterol stones, including immunohistochemical staining against apolipoprotein A-1. AB - Apolipoprotein A-1 is known to be one of inhibiting factors of cholesterol nucleation in bile, and decreased activity of apolipoprotein A-1 is considered to predispose cholesterol-supersaturated bile to formation of cholesterol crystals. To study the pathogenesis of the intrahepatic formation of cholesterol stones, we examined surgically resected liver specimens from six patients with intrahepatic cholesterol stones and compared the characteristic histopathological features with those of intrahepatic calcium bilirubinate stones, using morphological examination and immunohistochemical staining against apolipoprotein A-1. Morphologically, in all six patients with cholesterol stones the severity of chronic proliferative cholangitis with proliferation of the mucus-producing glandular elements in the walls of the large bile duct or periductal tissues was less extensive than that seen with calcium bilirubinate stones, and cholesterol crystals had formed in the septal and interlobular bile ducts. Immunohistochemically, unlike the normal liver and calcium bilirubinate stone containing lobes, the hepatocytes and the epithelial lining of the bile ducts and peribiliary glands of the cholesterol stone-containing lobes did not react completely (some of the epithelial cells reacted only faintly) with apolipoprotein A-1 antibody. These findings suggest that an abundance of mucous substance and bacterial infection of the biliary tree may not be necessary for the formation of cholesterol stones, compared with findings in cases of calcium bilirubinate stones. We suggest that cholesterol crystals may be produced in the septal and interlobular bile ducts in the microenvironment of cholesterol supersaturated bile and decreased activity of apolipoprotein A-1. PMID- 8477960 TI - Significance of pre-S region-defective hepatitis B virus that emerged during exacerbation of chronic type B hepatitis. AB - A defective form of the hepatitis B virus has been found in a patient with chronic type B hepatitis. Sequence analysis of the viral DNA after polymerase chain reaction amplification revealed a 117-base pair deletion (nucleotides 3129 53, subtype adr). This deletion includes the initiation codon of the pre-S2 region and a newly created in-frame stop codon in the pre-S1 region (nucleotide 3055) located 230 base pairs downstream from the pre-S1 initiation codon. This virus coexisted with the wild-type virus during the exacerbation period, as evidenced by an elevation of serum transaminase levels. It was not detected in the stable period, and the blood chemistry results were normal. We assayed antibodies against the mutation-related region by enzyme immunoassay in serial serum samples to clarify the mechanism of the emergence of this variant virus. Antibodies against the pre-S2 region were negative; however, the antibody response against the pre-S1 epitopes coincided with the appearance of the variant virus. These findings suggest that an activated T-cell and B-cell response had developed against the pre-S1 region during hepatic inflammation in this patient and that, consequently, selection occurred for a pre-S antigen-defective mutant strain of the virus that might be resistant to such an immune response. PMID- 8477961 TI - A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study. AB - A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen. PMID- 8477962 TI - Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. AB - We have previously shown in a 2-yr controlled trial that hypercholesterolemia, frequent in primary biliary cirrhosis, is lowered by ursodeoxycholic acid (13 to 15 mg daily). To further investigate this effect, we analyzed the influence of long-term ursodeoxycholic acid administration on serum lipids, lipoproteins and bile acids. The study involved a subgroup of 33 noncirrhotic patients (17 received ursodeoxycholic acid and 16 received a placebo) analyzed at inclusion and after 2 yr. The total serum cholesterol concentration was markedly reduced in the ursodeoxycholic acid-treated patients in comparison with the controls (mean +/- S.E.M. = 7.49 +/- 0.42 mmol/L and 7.07 +/- 0.23 mmol/L at entry and 4.44 +/- 0.40 mmol/L and 6.89 +/- 0.27 mmol/L at 2 yr in the ursodeoxycholic acid and placebo groups, respectively; p < 0.02). Quantitatively, this decrease was mainly caused by a fall in low-density-lipoprotein cholesterol, but very low density lipoprotein cholesterol levels also fell significantly. High-density-lipoprotein cholesterol levels remained stable in both groups, but the high-density lipoprotein2/high-density-lipoprotein3 cholesterol ratio fell significantly during ursodeoxycholic acid treatment. No significant change occurred in total triglyceride or total phospholipid levels. In the treated group, the proportion of ursodeoxycholic acid increased (up to 60% of total circulating bile acids), whereas that of cholic and chenodeoxycholic acids fell significantly. In conclusion, the cholesterol-lowering effect of ursodeoxycholic acid could be related to an improvement of cholestasis, modifications in cholesterol metabolism or both. Changes in endogenous bile acid composition induced by ursodeoxycholic acid might be the common denominator of these two mechanisms. PMID- 8477963 TI - Compression of the common bile duct due to portal-vein thrombosis in polycythemia vera. AB - The case of a 56-yr-old patient with polycythemia vera who was initially seen with jaundice is reported. Compression of the common bile duct by choledochal varices was found to be the cause of the obstructive jaundice. This compression was successfully treated with placement of a plastic endoprosthesis across the stenosis during endoscopic retrograde cholangiopancreatography. The significance of choledochal varices in the evaluation of obstructive jaundice is emphasized. PMID- 8477964 TI - Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. AB - Serum bile acid levels and distributions were studied every 6 mo in patients with primary biliary cirrhosis who were randomly assigned to receive ursodeoxycholic acid (13 to 15 mg/kg/day) (n = 73) or a placebo (n = 73) over a 2-yr period. In the ursodeoxycholic acid group, ursodeoxycholic acid was the predominant serum bile acid at 6 mo and throughout the 2-yr treatment period. The total concentration of endogenous bile acids decreased with a reduction in cholic acid (in the ursodeoxycholic acid group and the placebo group, respectively [mean +/- S.E.]: 13.0 +/- 2.2 and 12.6 +/- 2.5 mumol/L at entry vs. 3.5 +/- 0.6 and 9.0 +/- 2.2 mumol/L at 2 yr; p < 0.002), chenodeoxycholic acid (in the ursodeoxycholic acid group and the placebo group, respectively: 12.1 +/- 1.7 and 12.7 +/- 2.3 mumol/L at entry vs. 5.8 +/- 0.8 and 10.7 +/- 2.2 mumol/L at 2 yr; p < 0.02) and 3 beta-hydroxy-delta 5-cholenoic acid. The concentration of deoxycholic acid did not change, whereas that of lithocholic acid increased significantly (in the ursodeoxycholic acid group and the placebo group, respectively: 0.63 +/- 0.06 and 0.81 +/- 0.12 mumol/L at entry vs. 1.26 +/- 0.12 and 0.90 +/- 0.15 mumol/L at 2 yr; p < 0.001). These changes were independent of the histological stage of the disease. Thus during ursodeoxycholic acid administration the liver was exposed to a lower level of endogenous bile acids and to an increased concentration of ursodeoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477965 TI - Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation. AB - The clinical significance and outcome of nonanastomotic strictures and dilatations involving only the biliary tree of the graft with a radiological appearance of biliary ischemia is unknown. Therefore we analyzed the grafts of 128 patients to evaluate the biochemical, radiological and histological features that prompted the diagnosis of ischemic-type biliary stricture and the clinical outcome of this complication. Ischemic-type biliary strictures were diagnosed in 25 patients (19%). Initial graft function was similar in all patients, whether or not this complication developed. Most ischemic-type biliary strictures occurred between 1 and 4 mo after orthotopic liver transplantation. However, the appearance of ischemic-type biliary stricture in the month after transplantation was predictive for a poor outcome in all six grafts with early onset of ischemic type biliary strictures. Eighteen patients (72%) were treated with biliary stents and repeated dilatations. Long-term patency was achieved in 88% of these patients. Repeat transplantation was performed in six patients (24%); five survived. Finally, patients with ischemic-type biliary strictures spent more time in the hospital during the first year after orthotopic liver transplantation than did patients without the complication (62 +/- 27 days vs. 37 +/- 20 days; p < or = 0.001). This was due to repeated hospitalizations and a higher incidence of retransplantation. One-year graft survival was lower in patients with ischemic type biliary strictures than in patients without ischemic-type biliary strictures (69% vs. 88%; p = 0.006). However, 1-yr patient survival was similar in the two groups (91% vs. 89%). In conclusion, early appearance of ischemic-type biliary stricture features is associated with poor graft prognosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477966 TI - Augmented glucose use and pentose cycle activity in hepatic endothelial cells after in vivo endotoxemia. AB - Glucose use and pentose cycle activity were determined in freshly isolated rat hepatic endothelial cells 3 hr after an intravenous injection of Escherichia coli lipopolysaccharide (0.1 mg/kg body weight), by use of [1-14C]glucose, [6 14C]glucose and [2-3H]glucose. Lipopolysaccharide treatment in vivo increased glucose use fivefold, whereas glucose oxidation in the pentose cycle was elevated from 0.2 to 1.5 nmol/hr/10(7) cells. In vitro incubation of endothelial cells from saline- and lipopolysaccharide-treated animals in the presence of phorbol 12 myristate 13-acetate (10(-6) mol/L) increased pentose cycle activity twofold and eightfold, respectively. Phorbol 12-myristate 13-acetate caused only a 40% to 60% increase in glycolysis in both groups. Addition of t-butyl hydroperoxide (0.5 mmol/L), a substrate for glutathione peroxidase, caused a 24-fold and 16-fold increase in the glucose flux through the pentose cycle in cells from saline- and lipopolysaccharide-treated rats, respectively. Oxidation of glucose through the Krebs cycle was also increased several-fold after t-butyl hydroperoxide administration. Depletion of cellular glutathione by N-ethylmaleimide (0.1 mmol/L) inhibited the phorbol 12-myristate 13-acetate-induced or t-butyl hydroperoxide-induced increase in the pentose cycle activity with no marked effects on glycolysis. Diphenyleneiodonium (0.1 mmol/L), an inhibitor of superoxide and nitric oxide synthesis inhibited the phorbol 12-myristate 13 acetate-induced increased pentose cycle activity with no effects on the t-butyl hydroperoxide-induced response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8477967 TI - Decreased mitochondrial oxidation of fatty acids in pregnant mice: possible relevance to development of acute fatty liver of pregnancy. AB - Severe impairment of the beta-oxidation of fatty acids, as a consequence of a single factor or a combination of different causes, leads to microvesicular steatosis of the liver. In an effort to understand the mechanism(s) leading to the development of acute fatty liver of pregnancy in some women, we determined the effects of pregnancy on the mitochondrial oxidation of fatty acids in mice. In vivo, the rate of oxidation of the whole fatty-acid chain length was determined by measuring the rate of exhalation of [14C]CO2 after intragastric administration of a tracer dose of [U-14C]palmitic acid. [14C]CO2 exhalation was not significantly decreased at 14 days of gestation, but it had declined by 40% at 18 days of gestation (i.e., 24 to 48 hr before delivery). The rate of first beta-oxidation cycle was assessed by measuring the rate of [14C]CO2 exhalation after administration of [1-14C]octanoic acid, [1-14C]butyric acid or [1 14C]palmitic acid. [14C]CO2 exhalation had declined by 60%, 46%, and 24% after administration of [1-14C]octanoic acid, [1-14C]butyric acid and [1-14C]palmitic acid, respectively, in 18-day-pregnant mice. Total hepatic lipids and triglycerides, expressed per gram of liver, remained unchanged in 18-day-pregnant mice. In vitro, the rate of mitochondrial beta-oxidation (expressed per milligram of protein) had decreased by 47% at 18 days' gestation with [U-14C]palmitic acid as substrate and by 33% with [1-14C]octanoic acid but remained unchanged with [1 14C]palmitic acid. The activity of the tricarboxylic acid cycle, assessed by the formation of [14C]CO2 from [1-14C]acetic acid, had decreased by 24%. We conclude that the mitochondrial oxidation of fatty acids decreased during late-term pregnancy in mice as a consequence of both decreased mitochondrial beta-oxidation of medium-chain fatty acids, and decreased activity of the tricarboxylic acid cycle. We suggest that this effect, in combination with other factors, may contribute to the development of fatty liver of pregnancy in some pregnant women. PMID- 8477968 TI - Hepatic stimulator substance protects against acute liver failure induced by carbon tetrachloride poisoning in mice. AB - Hepatic stimulator substance was extracted from the liver of weanling Sprague Dawley rats according to the method of LaBrecque. Quang-Ming mice were injected with carbon tetrachloride to induce acute liver failure. Hepatic stimulator substance suppressed the elevation of ALT and AST induced by carbon tetrachloride in a dose-dependent manner. Hepatic histological changes indicated that hepatic stimulator substance reduced the severity of hepatic lesion induced by carbon tetrachloride and reversed carbon tetrachloride-induced reduction of hepatic mitochondrial succinic dehydrogenase activity. In attempting to elucidate the mechanism or mechanisms of this protective effect, we found that hepatic stimulator substance significantly restored the carbon tetrachloride-induced decrease of hepatocyte plasmalemma and mitochondrial and microsomal membrane fluidity. Hepatic stimulator substance also decreased the malondialdehyde content of carbon tetrachloride-intoxicated mice; restored the liver-reduced glutathione content, which was lowered by carbon tetrachloride intoxication; stimulated liver regeneration, as shown by enhanced DNA synthesis; and increased the 3H-thymidine incorporation into DNA of hepatocytes. We propose that hepatic stimulator substance protects the liver against acute liver failure induced by carbon tetrachloride poisoning, probably by an antioxidative effect on hepatocyte membrane lipid peroxidation, which was increased by free radicals produced from carbon tetrachloride. In addition, hepatic stimulator substance stimulates hepatocyte proliferation. These protective mechanisms may act in concert to protect against carbon tetrachloride injury. PMID- 8477969 TI - Cellular heterogeneity in binding and uptake of low-density lipoprotein in primary rat hepatocytes. AB - Hepatocellular heterogeneity of biochemical function is well established for many aspects of liver metabolism. This study addresses the question of cellular heterogeneity in the catabolism of low-density lipoprotein by rat hepatocytes. Low-density lipoprotein binding (4 degrees C) and uptake (37 degrees C) by rat hepatocytes were studied by use of human low-density lipoprotein labeled with a highly fluorescent lipophilic probe, N,N-dipentadecylaminostyrylpyridinium iodide, recently developed by us. Single-cell suspensions derived from rat hepatocytes in primary culture and from liver perfusion were studied with flow cytometry with and an approximation algorithm for data analysis. These studies show subpopulations of cells negative and positive for the specific binding and uptake of low-density lipoprotein. Dissociation constants for low-density lipoprotein binding and uptake were determined for the total population (18 micrograms/ml, binding; 12 micrograms/ml, uptake) and found to be in good agreement with previously reported values. Additionally, the dissociation constant for binding for the positive subpopulation was determined and found to be 3 micrograms/ml. This lower value is more typical of the values seen in other cell types. These findings are strongly suggestive of functional heterogeneity in the hepatic catabolism of low-density lipoprotein. PMID- 8477970 TI - Decrease in the hepatic clearance of hepatocyte growth factor in carbon tetrachloride-intoxicated rats. AB - To examine whether a decrease in hepatic uptake, clearance or both of hepatocyte growth factor contributes to increased plasma hepatocyte growth factor levels, we kinetically analyzed hepatic hepatocyte growth factor handling using rats with carbon tetrachloride-induced liver injury in both in vivo and perfused liver systems. After the intravenous administration of tracer 125I-hepatocyte growth factor, the time profile of trichloroacetic acid-precipitable 125I-hepatocyte growth factor was analyzed, and tissue clearance and total body plasma clearance were determined. For the tissues examined (liver, kidney, lung, spleen and adrenal), liver and adrenal clearance of 125I-hepatocyte growth factor decreased significantly. It was found that the hepatic clearance explains the bulk of the total body plasma clearance. The hepatic clearance and the total body clearance decreased to minimums (approximately 40% of control) 24 hr after carbon tetrachloride administration and recovered to near-control values over a 6-day period. At 24 hr after carbon tetrachloride administration, a single-pass liver perfusion of 125I-hepatocyte growth factor was performed, and its results were compared with the control results. After a 15-min perfusion of 125I-hepatocyte growth factor, we washed the liver sequentially with heparin and then with acid buffer to separately determine the cell-surface-bound and internalized 125I hepatocyte growth factor. In carbon tetrachloride-intoxicated rats, both the acid washable binding and the internalized 125I-hepatocyte growth factor dropped to almost half of the control values, but the decrease in heparin-washable binding was minimal. In contrast, when 125I-hepatocyte growth factor was perfused with excess unlabeled hepatocyte growth factor (135 pmol/L), mostly saturating the cell-surface receptors, the change in cell-surface-bound 125I-hepatocyte growth factor and internalized 125I-hepatocyte growth factor in carbon tetrachloride intoxicated rats was minimal. This finding, along with our previous finding that the cell-surface hepatocyte growth factor receptors are greatly down-regulated in carbon tetrachloride-intoxicated rats, suggests that the hepatic clearance of hepatocyte growth factor through receptor-mediated endocytosis decreases in carbon tetrachloride-intoxicated rats. The decrease in the hepatic clearance of hepatocyte growth factor could be one of the causes of the elevated hepatocyte growth factor level in the circulating blood in liver diseases. PMID- 8477971 TI - Time course of ethanol-induced impairment in fluid-phase endocytosis in isolated rat hepatocytes. AB - The time-course effects of long-term ethanol administration on fluid-phase endocytosis were studied in isolated rat hepatocytes. Rats were pair-fed an ethanol-supplemented liquid diet or an isocaloric control diet for 3 days, 1 wk, 2 wk or 5 wk. Hepatocytes were isolated and incubated at 37 degrees C with various concentrations of the fluid-phase marker Lucifer yellow. Net internalization of the marker dye was determined. After as little as 1 wk, ethanol-fed rats demonstrated marked decreases in the net internalization of dye compared with pair-fed controls; these changes persisted throughout 5 wk of feeding. Because net internalization is the balance between uptake into the cells vs. efflux from the cells, these components were examined individually. Early uptake was not significantly decreased by ethanol feeding; however, efflux of preloaded Lucifer yellow from cells from the ethanol-fed animals was markedly faster than efflux from pair-fed controls. This increased efflux was more prominent in the longer preload time (90 min) compared with a shorter preload time (15 min), indicating an alteration in dye distribution among various intracellular pools. These ethanol-induced changes in fluid-phase endocytosis were apparent for 1 wk through 5 wk of feeding and were similar for all Lucifer yellow concentrations examined. These results indicate that the decreased net internalization of Lucifer yellow through fluid-phase endocytosis is mainly a result of an ethanol-induced increase in efflux possibly caused by altered intracellular trafficking rather than by reduction in uptake. PMID- 8477972 TI - Effect of hypoxia on the hepatic metabolism of lidocaine in the isolated perfused pig liver. AB - The metabolism of lidocaine to monoethylglycinexylidide has been found useful as an indicator of liver function in association with liver transplantation. It has been postulated that this is due to the common effect of hypoxic damage on liver function and lidocaine metabolism. The effects of hypoxia on the elimination of lidocaine and the formation of monoethylglycinexylidide and on indexes of liver function were investigated with the isolated perfused pig liver preparation. This study was performed at similar hepatic effluent lidocaine concentrations of approximately 5 micrograms.ml-1 in normoxic (n = 7) and hypoxic (n = 8) livers of similar mass harvested from male Landrace x Large White pigs and perfused at standard unit hepatic flow rates. Whole blood lidocaine extraction ratio was 0.63 +/- 0.02 in normoxic livers (30% O2 at oxygenator inflow). It was significantly less (0.23 +/- 0.03) in livers subjected to hypoxia (2% O2 at oxygenator inflow), as were hepatic clearance (57.1 +/- 2.1 vs. 20.3 +/- 3.1 ml.min-1.100 gm-1), intrinsic clearance (1,706 +/- 182 vs. 284 +/- 53 ml.min-1.100 gm-1) and monoethylglycinexylidide formation as indicated by monoethylglycinexylidide/lidocaine ratios in the hepatic venous effluent (0.379 +/- 0.061 vs. 0.073 +/- 0.014) (p < 0.01). Hepatic oxygen consumption, adenine nucleotide status and bile flow were significantly impaired by hypoxia. Whereas perfusate potassium concentration increased early, AST levels showed delayed increases and ALT levels showed no changes. These changes correlated strongly with hepatic lidocaine elimination (p < 0.01). We conclude that lidocaine metabolism may be an early indicator of severe hepatic hypoxia. PMID- 8477973 TI - Immunoelectron microscopy identification of early proliferating cells in rat liver tissue during hyperplasia induced by lead nitrate. AB - Recent studies have suggested that hepatic stem cells may be involved in at least some forms of liver epithelial growth. To obtain further information on this controversial hypothesis, we treated rats with lead nitrate to induce liver growth and identified the cells undergoing early DNA synthesis by bromodeoxyuridine immunohistochemistry, using both light and electron microscopic detection methods. Eight hours after an intravenous injection of lead nitrate 100 mumol/kg, DNA synthesis was detected in a few scattered hepatocytes and in nonparenchymal cells in portal connective tissue. At the light microscopic level, identification of nonparenchymal cells was limited to bile duct epithelial cells. Other cell types were also labeled, but their identity could not be established. At the ultrastructural level, however, four types of nonparenchymal cells were identified as containing bromodeoxyuridine immunogold particles. These four types included bile duct epithelial cells, fibroblasts, macrophages and nondescript periductular cells. These periductular cells displayed certain ultrastructural features of bile duct cells but did not line a lumen or display microvilli on their apical membrane, nor did they reside within the bile duct basement membrane. Because proliferation of nonparenchymal cells in portal areas preceded that of hepatocytes, it is suggested that the former reaction reflects a direct mitogenic effect of lead nitrate and not an adaptive growth response secondary to parenchymal enlargement. However, whether DNA synthesis in periductular cells or bile duct cells reflects activation of hepatic stem cells cannot be established from the present morphological observations. If so, such a progenitor compartment must be dormant because it does not seem to play a functional role in this and other forms of adult liver epithelial growth. PMID- 8477974 TI - Cholesterol cholelithiasis in the prairie dog: role of mucin and nonmucin glycoproteins. AB - The aims of this study were to examine the effect of exogenous prostaglandin on mucin secretion and to determine the role of nonmucin glycoproteins on gallstone formation in the prairie dog model of cholesterol cholelithiasis. The concentration of total glycoprotein and nonmucin glycoproteins was measured in gallbladder bile from four groups of prairie dogs fed a control diet or a diet supplemented with 1.2% cholesterol with or without simultaneous subcutaneous administration of prostaglandin E1. Cholesterol feeding resulted in an increased concentration of concanavalin-A binding-proteins in gallbladder bile associated with an increase in pronucleating activity in vitro. Treatment with prostaglandin E1 and cholesterol feeding was associated with a significant increase in the incidence of cholesterol gallstone formation. Prostaglandin E1 treatment in the cholesterol-fed animals increased biliary concentrations of total glycoprotein and concanavalin-A-binding glycoproteins. Therefore the increased biliary glycoprotein level in cholesterol-fed, prostaglandin E1-treated prairie dogs, which reflects higher levels of mucin and nonmucin glycoproteins, appears to be an important factor in gallstone formation. PMID- 8477975 TI - Effects of thyroxine on the expression of alcohol dehydrogenase in rat liver and kidney. AB - We studied the effect of thyroxine on alcohol dehydrogenase activity, immunoreactive protein levels and messenger RNA levels in the livers of thyroidectomized and sham-operated male rats. Effects on kidney alcohol dehydrogenase activity were also examined. Sham-operated rats injected with 100 micrograms thyroxine/kg/day, which induced hyperthyroidism, showed a 30% decrease in liver and a 40% decrease in kidney alcohol dehydrogenase activity compared with sham-operated rats injected with vehicle. Hypothyroid rats exhibited a 1.5 fold increase in alcohol dehydrogenase activity in liver and kidney compared with thyroidectomized rats injected with a replacement dose of 20 micrograms thyroxine/kg/day. We saw a twofold and a 2.5-fold higher level of alcohol dehydrogenase activity in liver and kidney, respectively, of hypothyroid rats compared with hyperthyroid rats. These effects were not accounted for by nutritional differences; daily food intake did not differ between groups. Immunoreactive protein levels as seen on Western blots varied in the same direction as enzyme activity. Northern-blot analysis showed higher levels of liver alcohol dehydrogenase messenger RNA in hypothyroid rats compared with euthyroid rats. These studies show that liver alcohol dehydrogenase activity and protein levels are modulated by thyroxine at pathophysiologically relevant levels and that this effect is not due to changes in food intake; kidney alcohol dehydrogenase activity is regulated in parallel. The change in alcohol dehydrogenase activity appears to be controlled in part by pretranslational mechanisms in hypothyroid animals and by posttranslational mechanisms in hyperthyroid animals. PMID- 8477976 TI - Administration of prostaglandin E1 analog reduces rat hepatic and Ito cell collagen gene expression and collagen accumulation after bile duct ligation injury. AB - Recent studies suggest that prostaglandin E may have the ability to suppress cytokine responsiveness. We examined the effects of prostaglandin E administration on several parameters of acute and chronic liver injury induced by bile duct ligation. Enisoprost, a prostaglandin E1 analog, was found to suppress early hepatic and Ito cell type I collagen gene expression without diminishing the induction of the fibrogenic cytokine transforming growth factor-beta. Overall liver inflammation and cell proliferation were not altered, suggesting that prostaglandin E acts distal to the initial injurious event(s). During later phases, drug administration reduced total collagen accumulation and type I collagen periductular infiltration associated with early nodule formation. PMID- 8477977 TI - New concepts in bilirubin chemistry, transport and metabolism: report of the Second International Bilirubin Workshop, April 9-11, 1992, Trieste, Italy. PMID- 8477978 TI - Primary cholesterol hepatolithiasis: a disease with a different pathogenesis. PMID- 8477979 TI - To ligate or sclerose: beginning of a new era in the management of esophageal varices? PMID- 8477980 TI - Omeprazole induction of cytochrome P-450IA2: the importance of selecting the appropriate human model. PMID- 8477981 TI - Bidirectional transport of glutathione in hepatocyte membranes: does glutathione efflux stimulate organic anion uptake? PMID- 8477982 TI - Use of natural interferon-beta in the treatment of acute hepatitis C. PMID- 8477983 TI - The clinical connection. Hospitals work to design information systems that physicians will use. PMID- 8477984 TI - Physicians using computers show lower resource utilization. PMID- 8477985 TI - Pioneering protocols. Hospitals test the computer's use in patient care decisions. PMID- 8477986 TI - Physician leader rallies support for information network. PMID- 8477987 TI - A doctor in the network. Physician links improve access to critical data. PMID- 8477988 TI - Military MDs pilot regional clinical system. PMID- 8477989 TI - Training physicians. Government to influence specialty mix, distribution. PMID- 8477990 TI - Out in front. Managed care helps push clinical guidelines forward. AB - Until recently, most managed care provider incentives were productivity-oriented, but an increasing number of plans are shifting the focus to quality. For hospitals, the question is whose clinical practice guidelines to follow. PMID- 8477991 TI - Leadership incentives. Support, education and pay attract medical staff leaders. PMID- 8477992 TI - Physicians and the ADA. Hospitals should examine policies and procedures. AB - Though they aren't usually considered hospital employees, physicians with staff privileges may be covered by the Americans with Disabilities Act. As a result, hospitals should examine carefully their procedures regarding physicians in the context of the ADA's requirements. PMID- 8477993 TI - Outpatient acceleration. 1992 survey traces continued ambulatory care growth. PMID- 8477995 TI - Data watch. HMOs continue to experience sporadic growth. PMID- 8477994 TI - Physician CEOs: ranks continue to grow. PMID- 8477996 TI - Robodoc: study tests robot's use in hip surgery. PMID- 8477997 TI - Dutch experts discuss access, bioethical issues. PMID- 8477998 TI - Wireless radio system reduces intercom noise. PMID- 8477999 TI - Physicians: the rate of change accelerates. PMID- 8478000 TI - Tension wanes between hospitals and MDs. PMID- 8478001 TI - Strategizing health care for an aging America. PMID- 8478002 TI - Development of a sequence-tagged site for the centromere of chromosome 10: its use in cytogenetic and physical mapping. AB - We sequenced the alphoid centromere probe p alpha 10RP8 (D10Z1), aligned it to three published consensus sequences, and developed a sequence-tagged site (STS), sJRH-2, based upon oligonucleotide primers having two 3' mismatches with these consensus sequences. Polymerase chain reaction (PCR) amplification using genomic DNA from a somatic cell hybrid panel representing all human chromosomes demonstrated amplification from only those cell lines containing chromosome 10. Fluorescence in situ hybridization of the amplified product demonstrated intense and specific hybridization of the PCR product to 10p11.1-q11.1. A human genomic yeast artificial chromosome (YAC) library was screened using the sJRH-2 PCR assay, and five clones were identified. Sequence analysis of one chimeric clone (consisting of DNA segments derived from chromosomes 5p and 10cen) confirmed specificity of the STS for the centromere of chromosome 10. sJRH-2 provides a convenient cytogenetic marker for chromosome 10, which will also be useful for physical mapping of the pericentromeric region of chromosome 10, a region that harbors the gene(s) for three forms of multiple endocrine neoplasia (types 2A, 2B, and familial medullary thyroid carcinoma). The GenBank accession number for the p alpha 10RP8 sequence is X63622. PMID- 8478003 TI - Detection of a cryptic paracentric inversion within band 11p13 in familial aniridia by fluorescence in situ hybridization. AB - We report the first familial case of dominantly inherited aniridia with a cryptic inversion within band 11p13. High-resolution chromosome analysis gave a suspicion of a tiny constitutional aberration around band 11p13 and fluorescence in situ hybridization using 11p cosmids successfully confirmed that the aniridia patients of this family have an inversion within band 11p13. The distal breakpoint of the inversion is telomeric to a candidate aniridia gene (AN2) and suggests that more genes might be involved in the etiology of aniridia. In situ hybridization is a powerful tool to detect cryptic rearrangements in sporadic or familial patients with aniridia. This family indicated the importance of careful observation of the 11p13 region of aniridia patients, even if the aniridia was autosomal dominantly inherited. PMID- 8478004 TI - Chromosomal localization of four human zinc finger cDNAs. AB - cDNA clones encoding zinc finger motifs were isolated by screening human placenta and T-cell (Peer) cDNA libraries with zinc finger (ZNF) consensus sequences. Unique cDNA clones were mapped in the human genome by rodent-human somatic cell hybrid analysis and in some cases in situ chromosomal hybridization. ZNF80 mapped to 3p12-3qter, ZNF7 was previously mapped to 8q24 and is here shown by in situ hybridization and use of appropriate hybrids to map telomeric to the MYC locus. ZNF79 mapped to 9q34 centromeric to the ABL gene and between a constitutional chromosomal translocation on the centromeric side and the CML specific ABL translocation on the telomeric side. ZNF77 mapped to 19p while ZNF78L1 (pT3) mapped to 19q. Chromosome 19 carries many ZNF loci and other genes with zinc finger encoding motifs; the pT3 clone additionally detected a locus designated ZNF78L2, which mapped to chromosome region 1p, most likely in the region 1p32 where the MYCL and JUN loci map. PMID- 8478005 TI - Human reciprocal translocations: is the unbalanced mode at birth predictable? AB - Two methods of prediction for the risk of unbalance at birth were tested on a large data base of reciprocal translocation (1376 families): the pachytene diagram predictive method (PDP method) and the discriminant method (D method). These method succeeded in correctly predicting the segregation mode in 66% of the data for the PDP method and in 80% of the data for the D method. The quality of chromosome material (in particular R bands) must be taken into account for more accurate prediction. Some difficulties still exist in predicting the 3:1 tertiary segregation mode, which can frequently be incorrectly classified as the adjacent 1 mode. PMID- 8478006 TI - Steroid 21-hydroxylase (P450c21): a new allele and spread of mutations through the pseudogene. AB - Lesions in the gene encoding the adrenal enzyme steroid 21-hydroxylase (P450c21) result in defective adrenal cortisol synthesis, often accompanied by aldosterone deficiency. The symptoms range from severe neonatal disease to inconspicuous symptoms in adulthood depending on the nature of the mutations. The 21 hydroxylase gene is present in close proximity to a highly homologous pseudogene, and both genes show variation in copy number between individuals. For complete DNA sequence characterization, we have applied selective polymerase chain reaction amplification and direct sequencing of all full-length steroid 21 hydroxylase genes present in individuals. Using healthy individuals with only one remaining steroid 21-hydroxylase allele as normal references, a new allele was found in two siblings, in whom clinical and laboratory findings demonstrated moderate enzyme deficiency. Full-length sequencing of this allele displayed an Arg 484 to Pro codon change in exon 10, in the same position as a previously identified GG to C mutation found in a patient with severe 21-hydroxylase deficiency. Arg 484 is located within a stretch of amino acids that are highly conserved between mammalian 21-hydroxylases. The finding of the presently reported 21-hydroxylase allele indicates that the GG to C mutation from the severely affected patient has arisen by a two-step mechanism, consisting of a G to C transversion accompanied by an adjacent G deletion. When sequencing 26 pseudogenes, both these mutations, which are not present in the pseudogenes hitherto reported, were found at low frequency together with a number of other polymorphisms. Thus, also rare mutations can spread via the pseudogene and can therefore be expected to arise independently in unrelated individuals. PMID- 8478007 TI - Nucleotide substitutions at the -6 position in the promoter region of the factor IX gene result in different severity of hemophilia B Leyden: consequences for genetic counseling. AB - Mutations in the promoter region of the factor IX gene result in hemophilia B Leyden, which is characterized by considerable improvement in the disease after puberty. We have found that distinct nucleotide substitutions at the -6 position in the Leyden-specific (LS) region are associated with a different severity of hemophilia B. The proband (aged 2) from one family is a severe hemophiliac with factor IX activity (F.IXC) and antigen (F.IXAg) levels less than 1.0 U/dl. F.IXC and F.IXAg levels in two affected uncles are approximately 30% of normal levels. The LS region was targeted for analysis because the phenotypes suggested the inheritance of a factor IX Leyden gene. An abnormal TaqI digestion pattern was found in amplified DNA from the proband, and sequencing showed a G(-6) to C transversion that was linked to the disease in the family. In another family, two brothers (aged 8 and 9) suffer from mild hemophilia with F.IXC ranging from 7 to 10 U/dl and F.IXAg from 3 to 4 U/dl. They are the only documented members of the family with a bleeding tendency. Denaturing gradient gel electrophoresis on amplified fragments from one of the patient's genomic DNA corresponding to the 8 exons and flanking sequences of the factor IX gene suggested a defect only in a segment from the 5' region. This segment showed an altered TaqI digestion pattern, and sequencing demonstrated a G(-6) to A transition that was traced to the patient's mother and a grandmother. The different phenotypes associated with the G(-6) to A purine nucleotide transition compared with a G(-6) to C transversion provide evidence that this area is directly involved in the regulation of the human factor IX gene expression in vivo by binding of regulatory factors. The ability to predict that the conditions of a hemophilia B patient will improve with age has important implications for genetic counseling of the family. Therefore, the LS region should always be included when scanning the factor IX gene for mutations. PMID- 8478008 TI - Partial physical map of human chromosome 21 from fibroblast and lymphocyte DNA. AB - A partial physical map of the human chromosome 21 including 26 genes and anonymous sequences was established by pulsed-field gel electrophoresis analysis of restriction fragments obtained from lymphocyte and fibroblast DNAs. The sizes of the restriction fragments obtained by total digestion with eight different enzymes were compared in these two tissues. Differences resulting from the variations in the methylation state of the restriction sites were frequently observed. These differences and partial digestions were used to estimate the order and the distances between genes and sequences. Six linkage groups were defined: D21S13-D21S16, D21S1-D21S11, D21S65-D21S17, (D21S55,ERG)-ETS2, BCEI D21S19-D21S42-D21S113-CBS-CRYA1, and COL6A2-S100B. For six intergenic distances the resolution of previous maps was significantly increased. PMID- 8478009 TI - The effect of the apolipoprotein E phenotype on plasma lipids is not influenced by environmental variability: results of a Dutch twin study. AB - We tested the influence of the apolipoprotein E (apoE) polymorphism on the intrapair differences in the levels of plasma cholesterol, plasma triglycerides, low density lipoprotein-cholesterol, apoB and apoE in monozygotic (MZ) twins, and estimated whether or not there was a interaction between the apoE polymorphism and environmental factors. In 65 MZ twin pairs, the intrapair differences in the measured lipoprotein parameters were similar in the different apoE phenotype classes. This indicates that the effect of the apoE polymorphism is not influenced by environmental variability between the MZ pair members and accordingly identifies the APOE gene as a "level" gene. PMID- 8478010 TI - A recombinant Friedreich's ataxia family. PMID- 8478011 TI - Chromosomal mapping of the human gene for the tricyclic antidepressant-sensitive noradrenaline transporter. AB - The neuronal Na(+)- and Cl(-)-dependent transporter for the neurotransmitter noradrenaline (NA) is the primary target for the tricyclic antidepressant desipramine. The NA-transporter belongs to a new gene family of structurally related Na(+)- and Cl(-)-dependent neurotransmitter transporters. In this study, the chromosomal localization for the gene encoding the human NA-transporter (h NAT) was determined. By hybridization of a panel of somatic cell hybrids and by fluorescent in situ hybridization to metaphase chromosomes, the hNAT gene was localized on chromosome 16q12.2. In addition, evidence is presented for an intron exon structure of the gene. PMID- 8478012 TI - Parathyroid hormone gene analysis in autosomal hypoparathyroidism using an intragenic tetranucleotide (AAAT)n polymorphism. AB - We have identified a polymorphic tetranucleotide consisting of (AAAT)n within the first intron of the parathyroid hormone (PTH) gene, and have used this to investigate the segregation of the PTH gene and idiopathic hypoparathyroidism in 7 affected and 21 unaffected members from three families. An association between the PTH locus and autosomal dominant idiopathic hypoparathyroidism in one family was excluded by observing recombination between the two loci. In the remaining two families with autosomal recessive idiopathic hypoparathyroidism, the PTH locus was not similarly excluded. We had previously demonstrated a donor splice site mutation of the PTH gene in one of these families, and PTH gene abnormalities were therefore sought in the second of these families. DNA sequence analysis of the three exons, together with 4 exon-intron boundaries and the promoter region of the PTH gene revealed no abnormalities, thereby indicating molecular pathology at another locus. Thus, our analysis of idiopathic hypoparathyroidism reveals genetic heterogeneity for this disorder. In addition, our identification of a microsatellite polymorphism of the PTH gene should help further segregation studies of this locus in families with parathyroid disorders. PMID- 8478013 TI - Identification of the 408 valine to methionine mutation in the low density lipoprotein receptor in a German family with familial hypercholesterolemia. AB - Familial hypercholesterolemia (FH) is caused by different mutations in the gene encoding the low density lipoprotein receptor (LDLR). In Caucasian patients, at least three single point mutations have been identified causing FH. The asparagine206 to glutamine, and valine408 to methionine mutations were originally described in Afrikaners and recently identified in Dutch FH patients. The proline664 to leucine mutations was previously identified in an FH homozygote of Asian Indian origin and later identified in patients from London. Any of these mutations can be identified using direct amplification of genomic DNA by the polymerase chain reaction (PCR) and restriction enzyme digestion of PCR products. In this study, 100 unrelated German FH patients were screened for these three mutations. The valine408 to methionine mutation was identified in one individual and subsequently in the hypercholesterolemic child of the proband. Haplotype analysis with 7 restriction fragment length polymorphisms (RFLPs) revealed that the mutant allele carried the same haplotype as the previously described patients in South Africa and the Netherlands. Our finding supports the previous assumption of the European origin of the mutation. PMID- 8478014 TI - Polymorphism of glucose dehydrogenase (GDH, EC 1.1.1.47): formal and population genetic data. AB - The polymorphism of glucose dehydrogenase (GDH) is demonstrated by isoelectric focusing of leucocyte extracts followed by enzyme staining. Segregation in 52 families with 145 children is consistent with the formal hypothesis of three common alleles, GDH*1, GDH*2 and GDH*3, at an autosomal locus GDH. Allele frequencies from 104 unrelated individuals from southwestern Germany were calculated as GDH*1 = 0.70, GDH*2 = 0.18 and GDH*3 = 0.12. PMID- 8478015 TI - G6PD Mediterranean accounts for the high prevalence of G6PD deficiency in Kurdish Jews. AB - The Jews of Kurdistan are a small inbred population with a high incidence of beta thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Recently, it was reported that the beta-thalassaemia in this population shows an unusual mutational diversity; 13 different mutations were identified, of which 4 had not previously been observed in any other population. In contrast, we now report that the G6PD deficiency, which has the highest known incidence in the world, and which affects about 70% of males, is almost entirely attributable to a single widespread mutation, G6PD Mediterranean. PMID- 8478016 TI - Epidemiological data on Werdnig-Hoffmann disease in Germany (West-Thuringen). AB - This study contains the largest body of epidemiological data on Werdnig-Hoffmann disease (acute infantile spinal muscular atrophy; ASMA) in West-Thuringen in Germany. The incidence of ASMA was calculated to be 1 in 10,202 live births. The prevalence was 1 in 595,362 of the general population (as of 31 December 1987). The study gives an unexpectedly high incidence rate confirming the suggestion that ASMA in Central and Eastern Europe might be more frequent than in Western Europe. However, we consider that this high incidence rate in West-Thuringen is a result of the almost complete ascertainment made possible because of the well organised and centralised health system existing in Thuringen over the last few decades. PMID- 8478017 TI - Absence of familial defective apolipoprotein B-100 in Israeli patients with dominantly inherited hypercholesterolemia and in offspring with parental history of myocardial infarction. PMID- 8478018 TI - The relationship between meiotic chromosome pairing and chiasma formation. PMID- 8478019 TI - Structure and homology of human C1q receptor (collectin receptor). AB - In this paper we report partial amino acid sequence for C1q receptor (C1qR). The N-terminal amino acid sequence of isolated C1qR and the sequences of peptides obtained by V8/trypsin digestion show a high degree of similarity to the cDNA derived amino acid sequence of a human protein which was initially reported as a component of RoSSA and subsequently as calreticulin. This sequence in turn shows homology with Onchocerca volvulus antigen (RAL-1) and B50 murine melanoma antigen. A component of approximately 53,000 MW, isolated from human spleen, was found to have identical mobility on SDS-PAGE to C1qR and identical N-terminal sequence, but a different overall charge. Human antibodies from Sjogren's syndrome patients did not recognize C1qR, but showed positive reaction with the purified 53,000 MW component from spleen. Rabbit antibodies against denatured C1qR, in contrast, recognized both C1qR and the purified 53,000 MW component. The 53,000 MW spleen component thus has an identical N-terminal sequence to calreticulin, and to the reported RoSSA component, and is recognized by antibodies in Sjogren's syndrome sera. The data obtained indicate that C1qR and the reported calreticulin/RoSSA component are similar but not identical molecules, which belong to the same protein superfamily. PMID- 8478020 TI - Biochemical characterization of murine Fc gamma RI. AB - The biochemical analysis of murine Fc gamma RI has been difficult because this receptor is co-expressed with other Fc receptors on the cell surface of myeloid cells and all precipitate together with immune complexes. To overcome this problem and to study cells which expressed Fc gamma RI and only this Fc receptor, stable transfection of Chinese hamster ovary (CHO) cells (Fc gamma RI-) with Fc gamma RI cDNA was performed thereby permitting biochemical characterization of Fc gamma RI in isolation from other Fc receptors. Studies of Fc gamma RI+CHO cells showed the mature Fc gamma RI to be a 70,000 MW single-chain receptor on the cell surface. The 70,000 MW molecule was also identified on the Fc gamma RI+ cell lines, J774 (a macrophage-like cell line), and 18.81 (a pre-B-cell line). Fc gamma RI was shown to be N-linked glycosylated and after deglycosylation to have a protein core of 49,000 MW. Fc gamma RI was found to be phosphorylated and after PMA stimulation, the level of phosphorylation was increased; serine residues in the cytoplasmic tail were identified as the phosphate acceptors. Thus, Fc gamma RI can now be definitely characterized as a 70,000 MW phosphoprotein. PMID- 8478021 TI - Nucleotide sequence analysis of CDR3 elements of a panel of anti-peptide monoclonal antibodies recognizing parathyroid hormone-related protein. AB - Nucleotide sequences of heavy (VH) and light (VL) chain variable region complementarity determining regions have been determined from in vitro amplified mRNA isolated from a panel of monoclonal antibodies (mAb) raised to a synthetic 34mer peptide representing the N-terminal portion of human parathyroid hormone related protein (PTHrP or parathyrin) reported to contain an immunodominant epitope. These mAb vary in affinity for the synthetic peptide and native PTHrP (Ka between 5.9 x 10(8) and 1.9 x 10(11)l/M). All 10 mAb studied were found were found to utilized restricted VH2, V kappa 2, JH4 and J kappa 1 family genes. Significant differences in the length and sequence of D elements were found; however 9/10 mAb utilize members of the DSP2 family. Significantly, two broad ranges of affinity could be determined based on the presence of Asp or Ala at residue 101 in JH. PMID- 8478022 TI - In vivo lymphokine production in experimental autoimmune uveoretinitis. AB - Experimental autoimmune uveoretinitis (EAU) is a well-characterized model of immune-mediated intraocular inflammation. The intraocular infiltrate in EAU consists predominantly of T lymphocytes. The in vivo production of interleukin-2 (IL-2), lymphotoxin and IL-4 by these T cells was investigated by in situ hybridization using cDNA probes to lymphokine mRNA. Localization of lymphokine mRNA was found simultaneous with disease onset in areas of T-cell infiltration. Positive signal was seen over cells in the uveal tract, retina and extraocular region. Less than 10% of the population of T cells defined immunohistochemically had positive localization of mRNA for these lymphokines. The number of positive cells was similar for each of the three probes and increased as the disease progressed. The findings suggest that these lymphokines are produced in vivo in immune-mediated intraocular inflammation and may play a role in the immunopathology seen in these conditions. PMID- 8478023 TI - Theiler's murine encephalomyelitis virus induces tumour necrosis factor-alpha in murine astrocyte cell cultures. AB - Cytokines have been postulated to exert an important modulatory and recruiting role in demyelination induced by Theiler's murine encephalomyelitis virus (TMEV) in SJL/J mice. Using a cytolytic bioassay and ELISA, we have detected and quantified a cytokine, tumour necrosis factor-alpha (TNF-alpha), in supernatants from astrocyte cultures infected in vitro with TMEV. TNF was detected only after TMEV-specific infection of astrocyte cultures (approximately 200-400 U/ml). In vitro TNF synthesis appeared in a dose- and time-dependent manner and was produced by both SJL/J (a strain susceptible to TMEV-induced demyelination) and BALB/c (a resistant strain) astrocytes. The precise nature of TNF activity was further assessed by fast protein liquid chromatography (FPLC) and antibody neutralization. These results indicate an active role for astrocytes as accessory immune cells in our experimental model for multiple sclerosis. PMID- 8478024 TI - Mucosal and systemic cellular immune responses induced by Toxoplasma gondii antigens in cyst orally infected mice. AB - This study was performed to determine the T-cellular immune responses following Toxoplasma gondii oral infection and to assess further toxoplasma antigens on their ability to stimulate in vitro mucosal and systemic T-cell immunity. Parasite-specific cellular immune responses in Peyer's patches (PP), in mesenteric lymph nodes (MLN) and in spleen (SPL) were investigated using a lymphoblastic transformation test following oral infection of mice with strain 76K cysts of T. gondii. An early toxoplasma sonicate-induced mucosal T-cell proliferation occurred in MLN and PP with a peak responsiveness on day 6 post infection (PI) and rapidly reached background levels on day 7 PI in PP and on day 8 PI in mesenteric lymph nodes. A later splenic cellular blastogenesis was observed from day 28 PI and persisted throughout the experiment (day 91). At the time of T-cell proliferation, FACS analyses revealed a decrease in the relative percentages of CD4+ and CD8+ T cells with a predominance of CD8+ lymphocytes which leads to an inversion of the CD4/CD8 ratios. We found that CBA/J is a high responder mouse strain in the induction of mesenteric and splenic T-lymphocyte blastogenesis compared to the intermediate responder BALB/c and low responder C57BL/6. Toxoplasma gondii antigens SAG1 (30,000 MW) and GRA4 (40,000-41,000 MW), which are known to induce locally IgA antibodies, are shown to stimulate primed mucosal T lymphocytes from CBA/J and BALB/c mice whereas no proliferation was demonstrated with C57BL/6 T cells. 229-242 peptide, derived from the deduced amino acid sequence of GRA4, only induces detectable proliferation of primed CBA/J T lymphocytes. Following oral experimental infection, the in vitro mesenteric response to a toxoplasma sonicate is dominated by a Th2-type cytokine pattern whereas a predominant Th1 cytokine response is observed in the spleen. Finally, in vitro stimulation of mesenteric T cells with the three defined toxoplasma antigens resulted in secretion of interleukin-5 (IL-5) and IL-6 (except for SAG1) and interferon-gamma (IFN-gamma) whereas no detectable IL-2 or IL-4 was observed. PMID- 8478025 TI - Expression of major histocompatibility complex class II antigens and levels of interferon-gamma, tumour necrosis factor, and interleukin-6 in cerebrospinal fluid and serum in Toxoplasma gondii-infected SCID and immunocompetent C.B-17 mice. AB - In order to investigate activation of the innate immune system in murine toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing toxoplasmosis, whereas CD4+ and CD8+ T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-gamma (IFN-gamma) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (NK) cells. In comparison to immunocompetent mice IFN-gamma levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of tumour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up regulation of MHC class II antigen on microglia was less pronounced in SCID mice, presumably due to reduced levels of IFN-gamma. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of toxoplasmosis although T cells are necessary to control the infection efficiently. PMID- 8478026 TI - Requirements for the induction of the interleukin-2 receptor complex in a human pre-T-cell line. AB - Cell line PER-117 is a T-cell receptor negative human T-cell line that can be induced to express a functional interleukin-2 receptor (IL-2R). Recombinant interleukin-1 (IL-1) as well as certain combinations of inducer substances could be shown to stimulate the expression of the p55 (alpha)-chain of the IL-2R in PER 117 cells. The synergistic increases in IL-2R alpha expression were demonstrated at the cell surface as well as at the mRNA level. The results suggested that in PER-117 cells IL-1 appears to induce expression of the alpha-chain by pathways that are different to activation via protein kinase C (PKC), and that drug induced cyclic AMP (cAMP) activation did not substitute for IL-1. We found that the regulation of mRNA for IL-2R beta (p75) differed significantly from that seen for IL-2R alpha. Moreover, the requirements for IL-2R alpha induction determined for this cell line differ from other human cell lines, which may reflect that there are distinct requirements for activation depending on the stage of differentiation and/or lineage of the cells. The PER-117 cell line provides a unique model to examine further the mechanism leading to induction of a functional IL-2R at an early stage of human T-cell differentiation. PMID- 8478027 TI - High-dose interferon-gamma alters the distribution of B lymphocytes and macrophages in rat spleen and lymph nodes. AB - Continuous intravenous infusion of rat interferon-gamma (IFN-gamma) for 3 days provokes profound alterations of splenic architecture in LEW rats. The marginal zone of the white pulp is almost totally depleted of B lymphocytes and the follicles are reduced to small remnants. IgM kappa + plasmablasts and plasma cells increase substantially in the outer periarteriolar lymphatic sheath (PALS) and in the splenic red pulp. In addition, marginal metallophilic and marginal zone macrophages are augmented, partially by proliferation. It is discussed whether the activation and proliferation of these macrophages prevent replenishment of the marginal zone and follicles with recirculating B cells. Changes in B lymphocyte and medullary macrophage distribution are also present in submandibular and mesenteric lymph nodes. PMID- 8478028 TI - Low responsiveness of hepatitis B virus-transgenic mice in antibody response to T cell-dependent antigen: defect in antigen-presenting activity of dendritic cells. AB - The experiments presented here were performed to evaluate immune responsiveness of hepatitis B virus (HBV)-transgenic mice (transgenic mice), as a model of HBV carrier state to a T-cell-dependent antigen, keyhole limpet haemocyanin (KLH). The transgenic mice which were completely unresponsive to hepatitis B surface antigen (HBsAg), responded poorly to KLH. The levels of anti-KLH antibodies (Ab) produced in vivo were significantly lower in transgenic mice compared with the normal control mice at respective immunizing doses of KLH. In addition, a little or no anti-KLH Ab production was detected in culture supernatants of KLH-primed transgenic mice spleen cells. KLH-primed T cells from normal and transgenic mice induced anti-KLH Ab production from transgenic B cells in the presence of antigen presenting spleen adherent cells (SAC) from normal mice, but not those from transgenic mice. Depletion of dendritic cells from normal mice-derived SAC completely abrogated the anti-KLH Ab response in transgenic spleen cell culture and their addition to the culture restored the response. Low efficiency of transgenic dendritic cells was demonstrated in sodium periodate (NaIO4)-induced non-specific and allogenic antigen-induced T-cell proliferation. Finally, cytofluorometric analyses showed a reduced Ia antigen expression on transgenic dendritic cells. These results indicate that low responsiveness of transgenic mice in specific-antibody response is not due to functional defects in T cells or B cells but rather to a defect of antigen-presenting activity of dendritic cells. PMID- 8478029 TI - Tumour necrosis factor-alpha augments the expression of Fc IgE receptor (Fc epsilon RII/CD23) on human monocytic cell lines and down-regulates interleukin-4 driven Fc epsilon RII expression on monocytes. AB - We investigated the expression of the low affinity Fc IgE receptor (Fc epsilon RII/CD23) on the human monocytic cell lines U937, THP-1, Mono-Mac-6, and cultured human peripheral blood monocytes under stimulation with human tumour necrosis factor-alpha (TNF-alpha) and other cytokines. Fc epsilon RII was demonstrated by flow cytometry analysis employing the anti-Fc epsilon RII monoclonal antibody 3 5. TNF-alpha alone had a weak but significant stimulating effect on the Fc epsilon RII expression on the cell lines U937 and THP-1, and very modestly on Mono-Mac-6 cells. TNF-alpha strongly synergized with interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). IFN-alpha per se was ineffectual, but was able to increase the TNF-alpha effect. Furthermore, the action of TNF-alpha was slightly augmented by human IL-6. Similar effects were noted with TNF-beta alone or in combination with other cytokines. Interestingly, on human monocytes TNF-alpha weakly reduced the basal level of Fc epsilon RII, and markedly diminished the IL 4-induced Fc epsilon RII expression. Our results indicate that several cytokines may interact in a cytokine network to modulate Fc epsilon RII expression on monocytic cell lines. On human blood monocytes, TNF-alpha, like IFN-gamma or IL 6, counteracts the IL-4-induced Fc epsilon RII expression. These data suggest different regulatory pathways of Fc epsilon RII expression on blood monocytes and myelomonocytic cell lines. PMID- 8478030 TI - Two distinct types of cellular mechanisms in the development of delayed hypersensitivity in mice: requirement of either mast cells or macrophages for elicitation of the response. AB - Using mast cell-deficient mutant W/Wv mice and their normal counterpart we re evaluated the significance of participation of mast cells in allergic inflammatory response. W/Wv mice developed immediate hypersensitivity (IH) footpad reaction (FPR) to a somewhat lesser degree than the normal mice, suggesting that the mast cell might amplify the response. To exert classical tuberculin (tbc) delayed-type hypersensitivity (DTH) mast cells were not an essential cellular component. Vasoactive amines were essential to develop the response, but it did not necessarily originate from mast cells. When mice were immunized with methylated human serum albumin (MHSA) emulsified in incomplete Freund's adjuvant (IFA), mast cells were required to elicit DTH FPR. This was confirmed by the lack of the response in W/Wv mice, and the restoration of FPR by local transplantation of mature mast cells into mutant mice. This mast cell dependent (MD) DTH was different from tbc DTH as follows: mast cell dependency, macrophage dependency as revealed by ferritin sensitivity, kinetics of sensitization, effect of host's age and histopathology. Thus we concluded that there are two types of DTH in mice; one is macrophage-dependent tbc and the other is mast cell-dependent DTH. The correspondence of the DTH to the Jones-Mote (JM) DTH is discussed, although the dominance of mast cells in MD DTH lesion was not observed. PMID- 8478031 TI - Chemotactic desensitization of neutrophils demonstrates interleukin-8 (IL-8) dependent and IL-8-independent mechanisms of transmigration through cytokine activated endothelium. AB - We have recently shown that an exogenous gradient of interleukin-8 (IL-8) induces the transendothelial migration of neutrophils. Treatment of endothelium with the cytokines IL-1 or tumour necrosis factor (TNF) also causes neutrophil transmigration, and recent evidence suggests that this may be due to endogenous IL-8 produced by the endothelium. We have used specific chemotactic desensitization of neutrophils to investigate the role of IL-8 in transmigration through cytokine-activated endothelium. Preincubation of neutrophils with IL-8 reduced their chemotactic transmigration response to an IL-8 gradient by 81%, demonstrating desensitization. Transmigration in response to cytokine-activated endothelium was inhibited by 104% after IL-8 preincubation, thus tending to support the role of IL-8. However, preincubation with another neutrophil chemotactic factor N-formyl-methionyl-leucyl-phenylalanine (FMLP), which did not affect the IL-8, response, also inhibited transmigration, by 74%. This suggests that FMLP preincubation acts to inhibit a non-IL-8-dependent mechanism of transmigration through cytokine-activated endothelium. Chemotactic factor pretreatment of neutrophils did not reduce their adhesion to activated endothelium, but specifically blocked the transmigration step. We have therefore shown that chemotactic transmigration can be subjected to factor-specific desensitization, and have used this to provide evidence supporting a role for IL 8 in transmigration through cytokine-activated endothelium, as well as suggesting a further IL-8-independent mechanism. These data also provide a mechanism for the observed defect in accumulation of neutrophils at inflammatory sites when chemotactic factors are infused intravenously. PMID- 8478032 TI - An interspecies idiotope associated with the anti-cholera toxin response detected by a monoclonal auto-anti-idiotypic antibody. AB - We have produced an auto-anti-idiotypic (auto-anti-id) monoclonal antibody (mAb) which reacted with syngenic mouse polyclonal anti-cholera toxin (anti-CT) IgG antibody (Ab) and six/eight different anti-CT IgG mAb, but not with normal mouse BALB/c IgG. The binding of this auto-anti-id mAb on one anti-CT mAb was significantly inhibited by polyclonal anti-CT sera of rats, rabbits and mice. Thus the idiotope on anti-CT Ab recognized by this auto-anti-id mAb was public and expressed in different species. Because of the absence of competition between CT and this auto-anti-id mAb for the binding to the six anti-CT mAb, the anti-id mAb was classified as an Ab2 alpha. The efficiency of this auto-anti-id mAb to induce anti-CT Ab3 was tested with success in rabbits and rats. Auto-anti-id mAb immunized rats were significantly protected against an intraintestinal CT challenge. PMID- 8478033 TI - Follicle epithelial M cells are a source of interleukin-1 in Peyer's patches. AB - The production of interleukin-1 (IL-1) by rabbit Peyer's patch M cells populating the follicle-associated epithelium (FAE) was studied. Sorted 5D9+ phagocytic epithelial M cells synthesized IL-1 after stimulation with lipopolysaccharide (LPS) in vitro, as evidenced by the ability of culture supernatants to induce the proliferation of the T-cell line D10.G4.1. Fixed LPS-stimulated M cells were less effective at mediating T-cell proliferation than supernatants from LPS-activated M cells. The magnitude of T-cell proliferation was M-cell concentration dependent, and proportional to the dose of LPS. The M-cell-mediated D10.G4.1 cell proliferation was inhibited > 75% with anti-IL-1 alpha, but < 50% with similar concentrations of anti-IL-1 beta. The results show that M cells secrete IL-1, and suggest the participation of M cells in the delivery of a localized co stimulatory signal for T-cell and B-cell proliferation in the microenvironment of gut-associated lymphoid tissue (GALT). PMID- 8478034 TI - Sensitization of mice to chemical allergens modulates the responsiveness of isolated mast cells to IgE-dependent activation. AB - It is known that the release of granule-associated inflammatory amines by isolated mouse tissue-type mast cells is subject to regulation in vitro by a number of cytokines that are produced during the immune response. In this study we investigated whether mast cell secretory function might also be subject to regulation in vivo during active sensitization. Mice were sensitized with one of three chemical allergens (trimellitic anhydride, TMA; 2,4-dinitrochlorobenzene, DNCB; or oxazolone) all of which induce contact sensitization and one of which (TMA) in addition causes immediate hypersensitivity. Peritoneal mast cells isolated from treated mice and sensitized passively with IgE released a greater proportion of cellular serotonin (5-HT) on stimulation either by anti-IgE or by specific antigen than did cells isolated from vehicle-treated controls. These results show that the function of mast cells is susceptible in vivo to regulatory influences that result from induction of an immune response. PMID- 8478035 TI - Alterations in calcium metabolism in young people at risk for primary hypertension. The Dutch Hypertension and Offspring Study. AB - Several disturbances in calcium metabolism have been reported in primary hypertensive subjects. It is, however, not clear whether these alterations predate the development of hypertension or occur as a consequence of high blood pressure. We studied indexes of calcium metabolism in three groups of normotensive children with different familial predispositions for hypertension, based on parental blood pressure levels, with two, one, or no hypertensive parents. Plasma intact parathyroid hormone [1-84] was higher in the offspring of hypertensive parents compared with offspring of normotensive parents (difference, 0.58 pmol/L; standard error of the difference [SED], 0.24; p = 0.02). Mean serum calcium levels were slightly reduced in the offspring of two hypertensive parents (-0.019 mmol/L, SED = 0.013, p = 0.17). Plasma magnesium and phosphate levels were lower in the offspring of hypertensive parents (-0.032 mmol/L [SED = 0.016, p = 0.05] and -0.045 mmol/L [SED = 0.024, p = 0.05], respectively). Mean 1.25 dihydroxyvitamin D3 levels were similar among the groups. No differences in dietary intake of calcium, phosphate, or fiber were found. Urinary calcium excretion per 24 hours and the ratio of 24-hour urinary calcium excretion to daily calcium intake were somewhat higher in the offspring of hypertensive parents. Renal fractional excretion of calcium was similar in the offspring of two hypertensive parents, and renal fractional excretion of phosphate was lower in the offspring of two hypertensive parents compared with offspring of two normotensive parents (-1.50%, SED = 0.74, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478036 TI - Insulin resistance in young salt-sensitive normotensive subjects. AB - Insulin resistance has been demonstrated in patients with essential hypertension, and insulin-mediated sodium retention is believed to contribute to hypertension in these individuals. Recently, a hyperinsulinemic response to an oral glucose load has been found in salt-sensitive normotensive subjects, suggesting that insulin resistance may be present in these hypertension-prone individuals before the development of hypertension. In the present study, we examined the relation between insulin sensitivity and blood pressure response to salt intake in young, lean normotensive subjects on a high and a low salt diet. Insulin sensitivity was estimated by the "insulin suppression test," i.e., by measuring the plasma glucose and insulin concentrations achieved during a 180-minute infusion of somatostatin, insulin, and glucose in 18 healthy male volunteers (age, 21-28 years) given a standardized low salt diet (20 mmol/day) for 2 weeks, supplemented by either 220 mmol of NaCl per day or placebo in a single-blind randomized order for 1 week each. We defined salt sensitivity as a significant decrease in mean arterial blood pressure (> 3 mm Hg [p < 0.05]) measured for 60 minutes at 1 minute intervals on the low salt diet. By this definition, seven of the 18 subjects were salt sensitive. Although insulin infusion resulted in similar plasma insulin levels (approximately 50 milliunits/L) in both groups, concomitant glucose infusion resulted in plasma glucose levels that were more than 50% higher in the salt-sensitive than in the salt-resistant group (p < 0.005 by two-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478037 TI - Interleukin-2 causes endothelium-dependent contractions to arachidonic acid. AB - The present experiments were designed to investigate the effect of interleukin-2 on the response to arachidonic acid in rings with and without endothelium from Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) aortas. In control rings, arachidonic acid induced contractions of WKY aorta that were not different between preparations with and without endothelium. Incubation with interleukin-2 (10 units/mL) for 6 or 18 hours augmented the response to arachidonic acid in rings with, but not in those without, endothelium from WKY rat aortas. In the WKY aorta, both the endothelium-dependent and endothelium-independent contractions to arachidonic acid observed after incubation with interleukin-2 were abolished by indomethacin and ridogrel (a thromboxane-endoperoxide receptor antagonist and a thromboxane synthase inhibitor) but were not affected by dazoxiben (a thromboxane synthase inhibitor). Interleukin-2 did not augment the vascular reactivity of WKY aortic smooth muscle to activation of the thromboxane-endoperoxide receptor with U46619. In aortas from SHRs, arachidonic acid evoked endothelium-dependent contraction; interleukin-2 did not modify the response to arachidonic acid in preparations with and without endothelium. These data demonstrate that 1) endothelium-dependent contractions to arachidonic acid are observed in SHR but not in WKY rat aortas; 2) interleukin-2 induces endothelium-dependent contractions to arachidonic acid in the WKY aorta that are mediated by an augmented release of a metabolite of cyclooxygenase, different from thromboxane A2 but activating thromboxane-endoperoxide receptors; and 3) interleukin-2 does not affect the endothelium-dependent and endothelium-independent response to arachidonic acid in the SHR aorta. PMID- 8478038 TI - Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate salt hypertensive but not in spontaneously hypertensive rats. AB - Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced in the endothelium of blood vessels that may play an important role in the control of local blood flow and could be involved in the pathogenesis of hypertension. We investigated immunoreactive ET-1 (ir-ET-1) levels in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt and spontaneously hypertensive rats. We found that segments of thoracic aorta and the mesenteric vascular bed contain significantly more ir-ET-1 (11.84 +/- 0.84 and 17.30 +/- 1.89 fmol, respectively) than uninephrectomized control rats (1.78 +/- 0.20 and 9.19 +/- 0.63 fmol, respectively; p < 0.001). High performance liquid chromatography showed that ir-ET-1 of blood vessels of DOCA-salt hypertensive rats eluted in the same position as synthetic ET-1. Significantly increased ir-ET-1 was localized by immunohistochemistry in endothelial cells of aorta and large and small mesenteric arteries of DOCA-salt hypertensive rats. In contrast to the latter, in spontaneously hypertensive rats, vascular content of ir-ET-1 was similar to that of blood vessels of Wistar-Kyoto control rats, at both 6 and 16 weeks of age. High levels of vascular ET-1 may explain the downregulation of vascular endothelin receptors previously described in DOCA-salt hypertensive rats. Furthermore, this suggests that ET-1 may be involved in the maintenance of high blood pressure in mineralocorticoid hypertension. PMID- 8478039 TI - Pressor reactivity to norepinephrine and angiotensin in salt-sensitive hypertensive patients. AB - The mechanisms responsible for increased blood pressure in response to a high dietary sodium intake in salt-sensitive patients with essential hypertension are only partially understood. The possibility that increased reactivity to pressor hormones might contribute to hypertension in these patients has not been adequately investigated. We studied 11 salt-sensitive and 15 salt-resistant patients with essential hypertension while they were ingesting a diet with 20 meq/day sodium for 9 days or one with 200 meq/day sodium for 14 days. During the last 4 days of each dietary regimen, they received 30 mg/day of slow-release nifedipine. Blood pressure response to increasing doses of norepinephrine and angiotensin II (Ang II) was studied at the end of each of four phases of the study. Salt-sensitive patients exhibited a greater blood pressure response to norepinephrine than salt-resistant patients, irrespective of the dietary sodium intake and whether we took into account the dose infused or the actual plasma levels of norepinephrine achieved during the infusion. The blood pressure response to Ang II, on the other hand, was greater in salt-sensitive than salt resistant patients during low but not during high sodium intake. The blood levels of norepinephrine achieved during the infusion of this hormone were lower in salt sensitive than in salt-resistant patients. These studies indicate that an increased reactivity to the pressor action of norepinephrine might contribute to the maintenance of hypertension in salt-sensitive patients. The increased reactivity appears to be specific for norepinephrine. In fact, we observed increased reactivity to Ang II during low but not during high sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478040 TI - Effects of weight reduction on cellular cation metabolism and vascular resistance. AB - The early stages of weight loss are associated with a reduction in blood pressure, and the mechanisms mediating this reduction remain unclear. Platelet free calcium levels, [Ca2+]i, have been reported to be elevated in essential hypertension and to decrease with pharmacological treatment of the hypertension. In the current study, 18 obese subjects had measurements of blood pressure, forearm blood flow, forearm vascular resistance, and both basal platelet [Ca2+]i and [Ca2+]i responses to vasopressin during 12 weeks on a very low calorie (3,360 kJ, or 800 kcal) diet. Weight reduction was associated with reduction in mean arterial blood pressure at 3-4 weeks. There were associated reductions in forearm vascular resistance and platelet [Ca2+]i as well as increases in forearm blood flow at 3-4 weeks of the diet. Increased forearm blood flow was correlated with weight loss. Vasopressin-induced platelet [Ca2+]i responses increased, which correlated with the reduction in mean arterial pressure at 7-8 weeks of weight loss. Assuming that platelet [Ca2+]i metabolism reflects vascular smooth muscle cell [Ca2+]i metabolism, the data suggest that blood pressure reduction after weight loss may be related to reduced vascular smooth muscle cell [Ca2+]i. The reason for the increased vasopressin-induced [Ca2+]i after weight reduction is unclear. PMID- 8478041 TI - Cyclosporine and oxidized lipoproteins affect vascular reactivity. Influence of the endothelium. AB - Cyclosporine and in particular oxidatively modified low density lipoproteins can both exert direct vasoconstricting effects. We hypothesized that coincubation of arteries with low density lipoproteins and cyclosporine would enhance their respective influence on vascular tone. Therefore, we investigated vascular reactivity of isolated intact rabbit renal arteries preincubated with cyclosporine in the presence of native and oxidized low density lipoproteins. After preincubation of the arteries with cyclosporine (10 micrograms/ml, 90 minutes), unstimulated vascular tone as well as norepinephrine-induced vasoconstrictions remained unchanged compared with controls preincubated with the cyclosporine solvent dimethyl sulfoxide. Oxidized low density lipoproteins (100 micrograms/ml) in the absence of cyclosporine significantly enhanced vasoconstrictions to threshold concentrations of norepinephrine (78 +/- 10 microns at 30 nM). However, after cyclosporine treatment, the oxidized low density lipoprotein-induced potentiation of contractile responses to norepinephrine was further enhanced (157 +/- 19 versus 71 +/- 11 microns). Native low density lipoproteins had no influence on vascular tone. Potentiation of norepinephrine-induced vasoconstriction by oxidized low density lipoproteins took place in either endothelium-denuded or endothelium-intact arteries, whereas the further enhancement of vascular tone after cyclosporine treatment was seen only in endothelium-intact segments. Endothelium-dependent dilations to acetylcholine were fully preserved after treatment with oxidized low density lipoproteins and cyclosporine. Indomethacin, saralasin, and the thromboxane A2 antagonist daltroban had no influence, but the Ca2+ antagonist verapamil prevented the potentiation of vasoconstrictions by cyclosporine and oxidized low density lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478042 TI - Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study. AB - Ultrasonic backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. The integrated backscatter is also increased in hypertrophic cardiomyopathy, whereas it gives normal values in the physiological hypertrophy of elite athletes. We assessed the quantitatively evaluated myocardial reflectivity in 46 mild to moderate, clinically uncomplicated essential hypertensive patients, with echocardiographically assessed normal regional and global left ventricular function, and 22 age- and sex-matched normotensive control subjects. With an echo prototype implemented in our institute, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal of myocardial walls were normalized for those of the pericardial interface and expressed as a percent (integrated backscatter index). Hypertensive patients and control subjects differed in mean blood pressure (119 +/- 11 versus 95 +/- 5 mm Hg, p < 0.001) and left ventricular mass index (134 +/- 31 versus 105 +/- 21 g/m2, p < 0.001). However, integrated backscatter index overlapped for both the septum (28 +/- 17% versus 25 +/- 6%, p = NS) and the posterior wall (13 +/- 7% versus 13 +/- 4%, p = NS). In the hypertensive group, there was no detectable correlation between septal integrated backscatter index and either septal thickness (r = -0.26, p = NS) or mean arterial pressure (r = -0.14, p = NS). Hypertensive patients showed a normal pattern of quantitatively assessed ultrasonic backscatter, even in the presence of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478043 TI - Implications of the systolic hypertension in the elderly program. The Systolic Hypertension in the Elderly Program Cooperative Research Group. AB - Several imperatives drive the need to establish the merit of treating isolated systolic hypertension in the elderly. These include its higher prevalence with age, the associated excess cardiovascular risks, and the rapid aging of the population. The Systolic Hypertension in the Elderly Program demonstrated a significant reduction in stroke incidence (fatal and nonfatal) (36%, equivalent to preventing 30 strokes per 1,000 participants per 5 years). A 27% reduction in coronary heart disease incidence and a 32% reduction in all major cardiovascular events were also achieved (equivalent to the prevention of 16 and 55 events per 1,000 participants per 5 years, respectively). These results were associated with a treatment regimen in which the primary agent was low-dose chlorthalidone. The benefits accrued to all subgroups identified based on baseline age, race and sex, blood pressure, serum cholesterol levels, and electrocardiographic abnormalities. The reduction in coronary disease is consistent with predictions based on prospective epidemiological studies and is concordant with other recent intervention trials. It is a reasonable inference from the Systolic Hypertension in the Elderly Program findings that middle-aged as well as older people with isolated systolic hypertension, and people with less severe degrees of this condition, particularly when other risk factors are present, would benefit from such therapy. Another reasonable implication of the trial relates to the matter of preferred drug treatment regimens for diastolic hypertension, in middle-aged as well as older people.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478044 TI - Heparin has an inhibitory effect on endothelin-1 synthesis and release by endothelial cells. AB - We studied the inhibitory effects of heparin on basal and agonist-induced endothelin-1 biosynthesis and release from cultured bovine endothelial cells. Heparin dose-dependently and similarly inhibited endothelin-1 release, inositol trisphosphate production, and intracellular free Ca2+ levels stimulated by thrombin. Hirudin fragment had an inhibitory effect on thrombin-induced endothelin-1 release, whereas anti-thrombomodulin antibody had no effect. Heparin completely blocked phorbol ester-induced endothelin-1 release, whereas it had a partial inhibitory effect on endothelin-1 release stimulated by angiotensin and vasopressin. Northern blot analysis using complementary DNA for bovine preproendothelin-1 as a probe revealed that heparin reduced not only the basal but also the stimulated expression of preproendothelin-1 messenger RNA by thrombin and phorbol ester. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on the biosynthesis and release of endothelin-1, possibly by inhibiting protein kinase C-dependent pathway. PMID- 8478045 TI - Sustained hypertension induced by orally administered nitro-L-arginine. AB - To study the hemodynamic and metabolic effects of chronic inhibition of endothelium-derived nitric oxide, we treated conscious rats with an oral solution of N omega-nitro-L-arginine (LNA), an inhibitor of nitric oxide production by endothelial cells. After 3 days of treatment with 2.74 mM LNA, rats had higher blood pressures (136 +/- 5 versus 113 +/- 3 mm Hg, p < 0.0005) than did the control animals. This effect was maintained through 7 days of treatment (142 +/- 6 versus 109 +/- 4 mm Hg, p < 0.0005) and in three animals for 35 days (167 +/- 7 mm Hg). The blood pressure rise was dose dependent. The hypertensive effect of oral LNA was not enhanced by the administration of 20 mg intraperitoneal LNA and was prevented by pretreatment with L-arginine, although L-arginine also caused a transient but significant increase in urinary sodium excretion. When LNA treatment was discontinued, blood pressure fell gradually, with an effective biological half-life of 4.2 days. Metabolic balance studies did not identify differences in sodium or potassium balance between treated and control animals. Plasma renin activity was lower in LNA-treated animals, and aldosterone concentrations tended to be lower. In contrast, atrial natriuretic factor levels and serum electrolyte concentrations were unchanged after 7 days of treatment with LNA. These data support the premise that endothelium-derived nitric oxide plays an important role in basal hemodynamic homeostasis. Oral administration of LNA may serve as a model of chronic nitric oxide-deficient hypertension and allow for the future study of endothelium dependence in hypertension. PMID- 8478046 TI - Mechanism of hypertriglyceridemia in Dahl rats. AB - Plasma triglyceride concentrations were shown to be higher in hypertensive (153 +/- 2 mm Hg) male Dahl salt-sensitive rats than in control Sprague-Dawley rats (122 +/- 2 mm Hg). These differences in triglyceride concentrations were seen when blood was drawn at 9 AM from unfasted animals (229 +/- 27 versus 111 +/- 8 mg/dL), at 1 PM after a 4-hour fast (186 +/- 13 versus 88 +/- 4 mg/dL), or at 9 AM after a 13-hour fast (151 +/- 6 versus 90 +/- 6 mg/dL), all p < 0.001. Total triglyceride secretion was also compared in groups of rats by determining the increment in plasma triglyceride concentration for 2 hours after blocking triglyceride removal from plasma by injecting Triton. Studies performed at 1 PM and 9 AM, after the 4- and 13-hour fast, demonstrated that total triglyceride secretion was greater (p < 0.05) in Dahl rats only when studied at 1 PM. Direct estimates of hepatic triglyceride secretion at 1 PM also demonstrated a significant (p < 0.02) increase in secretion rate by perfused livers from Dahl rats, due in part to their increased liver size. In addition, removal of prelabeled very low density lipoprotein-triglyceride in the intact rat was significantly (p < 0.05) decreased in Dahl rats. Lipoprotein lipase activity measured in skeletal muscle, heart, and adipose tissue was also significantly decreased at 9 AM and 1 PM (after 0 and 4 hours of fasting) in tissue from Dahl rats. These data confirm that Dahl rats have higher plasma triglyceride concentrations than Sprague-Dawley rats. Since both total and hepatic triglyceride secretion were somewhat greater in Dahl rats, in association with a decrease in both removal of very low density lipoprotein from plasma and decreased muscle and adipose tissue lipoprotein lipase activity, it seems likely that hypertriglyceridemia in Dahl rats results from a combination of increased triglyceride secretion and decreased triglyceride removal. PMID- 8478047 TI - Essential hypertension: a renal disease? A review and update of the evidence. PMID- 8478049 TI - Presence of a capsule in Vibrio vulnificus biotype 2 and its relationship to virulence for eels. AB - Strains of Vibrio vulnificus biotype 2, isolated from internal organs of diseased European eels as pure cultures of opaque cells, together with some reference strains from Japanese eels, were used in this study. Spontaneous translucent phase variants were obtained from the corresponding parent strains and compared for a variety of phenotypic traits related to virulence for eels. The rate of colony dissociation from opaque to translucent cells was higher (around 10(-2)) than that observed for translucent to opaque cells (10(-3) to 10(-4)). Electron microscopy with ruthenium red revealed the presence of a capsule of variable thickness on opaque cells, whereas translucent-type colonies had no observable capsular materials. No differences in plasmid profiles were detected between the two cell types so that plasmids do not seem to be implicated in the mechanism of phase shift of biotype 2 strains. No apparent difference in outer membrane protein and lipopolysaccharide patterns could be observed between the cell types. Both isogenic morphotypes were able to grow in eel serum and minimal medium supplemented with ethylenediamine di(O-hydroxyphenyl-acetic acid) or transferrin. Therefore, the presence of capsule was not required for the acquisition of iron from iron chelators or for resistance to serum bactericidal action. Both morphotypes were highly virulent for elvers, although the 50% lethal dose for translucent cells was higher than that for the corresponding opaque cells. The latter observation, together with the overall data, suggests that the production of capsular materials by biotype 2 of V. vulnificus is not essential for the development of vibriosis in eels, at least when cells are injected intraperitoneally. PMID- 8478048 TI - Pathogenicity of Helicobacter pylori: a perspective. PMID- 8478050 TI - Endotoxin-induced tumor necrosis factor alpha synthesis in murine embryo fibroblasts. AB - Murine embryo fibroblasts (MEF) were found to secrete tumor necrosis factor (TNF) in response to stimulation with endotoxin. Endotoxin-induced TNF production by MEF was inhibited by cycloheximide. However, reversal of the effect of this inhibitor on protein synthesis results in TNF being secreted in amounts equivalent to those produced by endotoxin-induced MEF not treated with cycloheximide. Actinomycin D treatment of MEF blocked the production of endotoxin induced TNF. Maximal production of TNF required MEF gene transcription during the first 6 h of incubation with endotoxin. To determine whether endotoxin-induced TNF alpha (TNF-alpha) and/or TNF beta were produced by MEF, cDNA was synthesized from the total RNA isolated from endotoxin-induced MEF and amplified by the polymerase chain reaction in the presence of oligonucleotide primers specific for each cytokine. On the basis of the polymerase chain reaction analysis, it was determined that TNF-alpha mRNA levels were increased in endotoxin-induced MEF. Thus, production of TNF-alpha by fibroblasts in response to the endotoxin component of bacterial cell walls is likely to contribute to the expression of TNF-mediated effects occurring in fibroblast-rich tissues infected with gram negative bacteria. PMID- 8478051 TI - Complement resistance of pathogenic Entamoeba histolytica mediated by trypsin sensitive surface component(s). AB - Pathogenic forms of the protozoan parasite Entamoeba histolytica were reported previously to resist the cytolytic effect of the alternative complement pathway (AP) only temporarily during exposure to complement. In contrast, nonpathogenic forms of E. histolytica had been found to show AP resistance as a stable property. We studied the mechanisms of AP resistance of the two forms. Upon exposure to AP activity, resistant pathogenic or nonpathogenic forms bound significantly less C3 products than complement-sensitive pathogenic amebae, indicating that the two resistant forms both inhibited AP amplification. Various enzymatic treatments and inhibition of membrane mobility by cytochalasin B and glutaraldehyde fixation showed that the mechanisms of AP inhibition differed between pathogenic and nonpathogenic forms; in contrast to nonpathogenic forms, pathogenic amebae required intact membrane mobility and a trypsin-sensitive surface component(s) to inhibit AP activation. PMID- 8478052 TI - Single and combined humoral and cell-mediated immunotherapy of Pneumocystis carinii pneumonia in immunodeficient scid mice. AB - Homozygous mutant scid/scid (severe combined immunodeficiency) mice (referred to as scid mice) lack both specific humoral and cell-mediated immune functions and are exemplary in vivo models for analysis of host-parasite relationships. In our colony, scid mice routinely and predictably develop spontaneous Pneumocystis carinii pneumonia (PCP) with high morbidity. Previous studies have identified both T cells (specifically, CD4+ cells) and antibody as independent mechanisms of effective anti-P. carinii resistance; however, CD4+ T cells also cause an often fatal hyperinflammatory reaction. The current study has explored the optimal application of these immune components for conferring protection against P. carinii. Anti-P. carinii hyperimmune serum was highly effective at reducing the number of P. carinii organisms in early, intermediate, and advanced stages of PCP and was capable of increasing the mean life expectancy of P. carinii-infected scid mice by more than threefold if provided on a continuing basis. When a short course of hyperimmune-serum therapy was provided prior to transfer of P. carinii sensitized normal lymphocytes, scid mice were rendered permanently free of P. carinii without the pathological sequelae of the hyperinflammatory reaction. These findings are discussed in the contexts of mechanism and clinical relevance. PMID- 8478053 TI - The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis. AB - Little is known of the pathophysiology of invasive pulmonary aspergillosis (IPA), an opportunistic fungal infection usually caused by Aspergillus fumigatus. It has been suggested that the ability of the fungus to degrade elastin may aid its invasion and growth in lung tissue. We have described previously the construction of a strain of A. fumigatus in which the gene encoding an alkaline protease, AFAlp, had been disrupted (C.M. Tang, J. Cohen, and D.W. Holden, Mol. Microbiol. 6:1663-1671, 1992); this mutant is deficient in extracellular proteolytic and elastinolytic activity over a broad pH range. In this study, we compared the pathogenicity of this and another AFAlp disruptant with their isogenic, elastase producing parental strains in two murine models of IPA. In both models, animals were inoculated via the respiratory tract. In the first model, the inoculum was delivered as airborne conidia and animals developed signs of respiratory distress within 2 to 4 days. In the second model, conidia were administered intranasally as a suspension and the disease developed over a 2-week period. No difference was observed between the wild-type and AFAlp disruptants in terms of mortality, and elastin breakdown was detected in lung tissue from animals inoculated with all four strains. We conclude that AFAlp is not a virulence determinant in these models of IPA. PMID- 8478054 TI - Anaerobic growth and cytidine 5'-monophospho-N-acetylneuraminic acid act synergistically to induce high-level serum resistance in Neisseria gonorrhoeae. AB - In vivo, gonococci encounter a myriad of conditions not present in vitro. At some stages of infection and disease, gonococci may grow anaerobically, probably by using sodium nitrite as a terminal electron acceptor. Also, gonococci sialylate their lipooligosaccharide (LOS) in vivo, by using low concentrations of cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) present in host tissue. This sialylation is responsible for the acquired resistance of gonococci to both normal and immune human serum. Given that gonococci grown in the absence of oxygen or in the presence of CMP-NANA probably more closely resemble gonococci grown inside a human host, we studied the serum resistance of gonococci cultivated under these conditions. In the absence of CMP-NANA, anaerobically grown (anaerobic) gonococci were somewhat less sensitive to serum killing than were aerobically grown (aerobic) gonococci. However, anaerobic gonococci grown with 6 micrograms of CMP-NANA per ml exhibited almost complete serum resistance, while aerobic gonococci required 16-fold-higher CMP-NANA concentrations to achieve significant serum resistance. Anaerobic gonococci incubated in CMP-NANA converted to serum resistance two to three times faster than did similarly treated aerobic gonococci and incorporated up to six times as much sialic acid into their LOS. Gonococci can express several different LOS molecules. Anaerobic gonococci expressed the LOS molecule that acts as an acceptor for sialic acid from CMP-NANA in greater quantity than aerobic gonococci did. Finally, Triton X 100 extracts of anaerobic gonococci contained about four times more sialyltransferase activity than did extracts of aerobic gonococci. Sialyltransferase activity in these extracts was not inhibited by oxygen or enhanced by anaerobiosis. These data indicate that anaerobic conditions lead to altered LOS biosynthesis and to induction of sialyltransferase activity in gonococci. In vivo, where decreased oxygen levels and relevant concentrations of CMP-NANA are found, gonococci could readily become resistant to killing by normal and immune human serum. PMID- 8478055 TI - Murine T-cell response to native and recombinant protein antigens of Rickettsia tsutsugamushi. AB - A polyclonal T-cell line with TH1 characteristics was used to assess the murine cellular immune response to native and recombinant Rickettsia tsutsugamushi antigens. Proliferation of this T-cell line was observed in response to numerous native antigen fractions, which indicates that the murine T-helper-cell response is directed at multiple scrub typhus antigens with no apparent antigenic immunodominance. Subsequent analysis of recombinant R. tsutsugamushi antigens made it possible to identify a 47-kDa scrub typhus antigen (Sta47) that was stimulatory for the polyclonal T-cell line. Recombinant clones encoding 56-, 58-, and 110-kDa antigens (Sta56, Sta58, and Sta110, respectively) were unable to induce proliferation of this T-cell line. DNA sequence analysis of the cloned rickettsial insert encoding the Sta47 protein revealed the presence of four open reading frames potentially encoding proteins of 47, 30, 18, and 13 kDa. Analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated and eluted fractions of lysates from the recombinant HB101(pRTS47B4.3) demonstrated that the fractions containing the 47-kDa protein as well as those containing proteins less than 18 kDa were stimulatory. Selected synthetic amphipathic peptides derived from the Sta47 antigen sequence identified a 20-amino-acid peptide that gave a 10 fold increase in T-cell proliferation over a control malarial peptide of similar length. Recognition of the 47-kDa antigen by a T-cell line with TH1 characteristics implicates this protein as one of potential importance in protection studies and future vaccine development. PMID- 8478056 TI - Safety, stability, and efficacy of noncapsulated mutants of Actinobacillus pleuropneumoniae for use in live vaccines. AB - Clonal, noniridescent mutants of Actinobacillus pleuropneumoniae serotypes 1 and 5 were isolated following chemical mutagenesis with ethyl methanesulfonate. The absence of any detectable capsule was confirmed by inhibition radioimmunoassay. There were no differences between the parent and mutant strains in lipopolysaccharide or protein electrophoretic profiles or in hemolytic activity. There was no detectable reversion to the encapsulated phenotype in vitro after passage in mice or pigs or in microporous capsules that were implanted subcutaneously in pigs for 6 weeks. The mutants were able to survive for more than 1 week in pigs following subcutaneous inoculation, which resulted in a strong immune response to whole cells and Apx toxins I and II. Intratracheal challenge of pigs with the serotype 5 mutant at a dose 1 log greater than the 50% lethal dose for the parent resulted in no clinical disease or lesions except in one pig that had slight pneumonia and pleuritis. Twenty-four hours after challenge, A. pleuropneumoniae could not be recovered from the respiratory tracts of any of the challenged pigs except for the one infected pig; this isolate remained noncapsulated. Immunization of pigs with one or both serotypes of noncapsulated mutants protected all pigs against clinical disease following intratracheal challenge with the virulent homologous or heterologous serotype. Nonimmunized control pigs and pigs immunized with a commercial bacterin died or had to be euthanized within 24 h of challenge. Thus, live noncapsulated mutants of A. pleuropneumoniae may provide safe and cost-effective protection against swine pleuropneumonia. These observations support the possibility that noncapsulated mutants of other encapsulated, toxin-producing bacteria may also prove to be efficacious live-vaccine candidates. PMID- 8478057 TI - Induction of macrophage-mediated production of tumor necrosis factor alpha by an L-form derived from Staphylococcus aureus. AB - We investigated the capability of an L-form derived from Staphylococcus aureus to induce tumor necrosis factor alpha (TNF-alpha) production in murine peritoneal macrophages. The activity for TNF-alpha induction was found in the membrane fraction of the L-form but not in the cytoplasmal fraction purified by the sucrose step gradient centrifugation. TNF-alpha mRNA was also detected in macrophages stimulated with L-form membranes. L-form induced TNF-alpha production in macrophages from both lipopolysaccharide-responsive and -unresponsive mouse strains. Regardless of the presence of polymyxin B, the activity of TNF-alpha induction of L-form was mostly found in the phenol layer, but not in the aqueous layer, both of which were prepared by phenol extraction method. Fractions of L form membranes representing molecular masses of approximately between 29 and 36 kDa were primarily responsible for inducing the production of TNF-alpha consistently. Moreover, this stimulatory effect was abolished by digestion with Streptomyces griseus protease. In Western blot (immunoblot) analysis with anti lipoteichoic acid antibody, two bands (65 and 45 kDa) were observed in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the phenol layer, whereas one band (14 kDa) was observed in either the aqueous layer or lipoteichoic acid of S. aureus. These results suggest that the component in the membrane of the L form, distinct from cell wall components such as teichoic acid or lipopolysaccharide, possesses the capability to stimulate TNF-alpha production by macrophages. PMID- 8478058 TI - Characterization of the Shigella flexneri ipgD and ipgF genes, which are located in the proximal part of the mxi locus. AB - The Shigella flexneri invasion process requires the synthesis of the Ipa proteins and their secretion by specific factors encoded by the mxi and spa genes, which are clustered upstream from the ipa operon. We report here the characterization of the ipgD, ipgE, and ipgF genes, which are located in the 5' end of the mxi locus. Analysis of IpgF-PhoA fusions endowed with high levels of alkaline phosphatase activity confirmed the functionality of a classical signal sequence detected in the sequence of IpgF. The ipgD and ipgF genes were each inactivated on the large virulence plasmid by insertion of a nonpolar cassette; each of the ipgD and ipgF mutants thus constructed showed the same invasive phenotype as the wild-type strain and was able to provoke keratoconjunctivitis in guinea pigs. It thus appears that two genes located at the ipa-proximal part of the mxi locus are not directly involved in invasion. Analysis of concentrated culture supernatants of the wild-type and ipgD strains indicated that secretion of one polypeptide, whose size was consistent with that predicted for the IpgD protein (60 kDa), was abolished in the ipgD mutant. PMID- 8478059 TI - Cytocidal effects of Escherichia coli hemolysin on human T lymphocytes. AB - Escherichia coli hemolysin is the prototype of a large family of pore-forming toxins produced by gram-negative organisms. Besides its known cytotoxic activities against granulocytes, monocytes, endothelial cells, and renal epithelial cells, we now demonstrate that the toxin potently kills human T lymphocytes. Evidence based on different and independent approaches indicates that lymphocidal activity is due to formation of transmembrane pores. Additionally, cells prestimulated with phytohemagglutinin respond to low doses of E. coli hemolysin with DNA fragmentation similar to that observed in cells undergoing programmed cell death. Kinetic considerations lead us to conclude that DNA degradation may, however, represent an epiphenomenon. Killing of T cells is another means through which E. coli hemolysin could directly impair host defense. PMID- 8478060 TI - Lipopolysaccharide from Brucella abortus behaves as a T-cell-independent type 1 carrier in murine antigen-specific antibody responses. AB - In order to determine the carrier nature of lipopolysaccharide from Brucella abortus (LPS-BA) in evoking humoral responses, normal and immunodeficient mice were immunized with trinitrophenyl (TNP)-conjugated LPS-BA (TNP-LPS-BA) and the responses were compared with those to known T-dependent and T-independent antigens. TNP-LPS-BA, like T-independent type 1 (TI-1) antigens such as TNP-BA and TNP-LPS from Escherichia coli (TNP-LPS-EC), generated anti-TNP responses in BALB/c, athymic BALB/c nu/nu, and CBA/N mice. In contrast, N-2,4-dinitrophenyl beta-alanylglycylglycyl-substituted keyhole limpet hemocyanin, a typical T dependent antigen, was not immunogenic in athymic mice, and TNP-Ficoll (T independent type 2) was ineffective in eliciting humoral responses in CBA/N mice. These results indicate that LPS from B. abortus acts as a TI-1 carrier in generating antibody responses. In C3H/HeJ mice, TNP-LPS-BA generated higher-titer immunoglobulin G1 (IgG1), IgG2a, and IgG2b anti-TNP antibodies than TNP-LPS-EC. Compared with those from BALB/c mice, pure resting B cells isolated from C3H/HeJ mice exhibited a 30-fold lower proliferative response to LPS-EC, whereas the LPS BA response was reduced to a lesser extent (5-fold). This suggests that the disparity observed in antibody titers was due to different abilities of LPS from B. abortus and E. coli to stimulate C3H/HeJ B cells. The ability of LPS from B. abortus to act as a carrier in generating humoral immune responses indicates that LPS-BA can be substituted for whole B. abortus organisms in vaccine development. PMID- 8478061 TI - Evidence for absence of the MPB64 gene in some substrains of Mycobacterium bovis BCG. AB - Substrains of Mycobacterium bovis BCG have been divided in two major groups, high producers and low producers of the secreted proteins MPB64 and MPB70. Of these, Mycobacterium tuberculosis secretes only the analog MPT64 during growth on Sauton medium. It has been confirmed that high-producer and low-producer substrains of BCG as well as M. tuberculosis contain the gene for the MPB/MPT70 protein. By contrast, polymerase chain reaction and hybridization experiments are reported here which indicate that the MPB64 gene is absent in the BCG substrains Copenhagen, Pasteur, Glaxo, and Tice, in which previous methods did not permit distinction between secretion of small amounts or absence of the protein in culture fluids. PMID- 8478062 TI - Haemophilus ducreyi adheres to but does not invade cultured human foreskin cells. AB - Haemophilus ducreyi is the etiologic agent of the localized genital ulcer disease known as chancroid. The pathogenesis of this organism is poorly understood. The role of attachment in the disease process has not been evaluated. In this study, 125I-H. ducreyi was used to quantitatively evaluate the interaction of virulent and avirulent H. ducreyi strains with human foreskin cells. Using this in vitro model system, we demonstrated that, at 22 and 35 degrees C, the attachment of virulent H. ducreyi 35000 to human foreskin cells was significantly more marked than that of avirulent H. ducreyi A77. Although H. ducreyi penetrated between human foreskin cells, internalization was not a major component. Our competition assay data suggest that the attachment mechanism of H. ducreyi may be similar to that of Neisseria gonorrhoeae. We speculate that the attachment and microcolony formation of virulent H. ducreyi may provide a mechanism for bacterial localization and evasion of host defenses. PMID- 8478063 TI - Effect of growth conditions on expression and antigenicity of Staphylococcus epidermidis RP62A cell envelope proteins. AB - Staphylococcus epidermidis RP62A (ATCC 35984) was grown in tryptic soy broth (TSB), iron-depleted TSB (TSB-Fe), iron-reconstituted TSB-Fe (TSB+Fe), a chemically defined medium, and fetal calf serum (FCS) and on silastic disks in chambers that were sutured to the pig peritoneal wall. Bacterial cell wall proteins were extracted by digestion with recombinant lysostaphin, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and detected by silver staining. Cell wall proteins from TSB-, chemically defined medium-, or FCS-grown cells had a complex profile of greater than 25 protein bands spanning the full molecular mass range. By contrast, a digest obtained from in vivo-grown cells had only five major proteins of 40 kDa or greater. Proteins of 130 and 106 kDa were present in the cell envelopes of TSB-Fe- and in vivo-grown cells but not in those grown in TSB or TSB+Fe. A 43-kDa protein expressed by in vitro-grown cells and 52 and 96-kDa proteins expressed by in vivo-grown cells reacted with antisera from pigs with the chamber implants and from catheterized, paracatheter-inoculated pigs but not with hyperimmune sera from pigs immunized with TSB-grown cells. The data indicate that S. epidermidis, growing under in vivo conditions, expresses antigens distinct from those that are grown in vitro. PMID- 8478064 TI - Characterization of a heat-modifiable outer membrane protein of Haemophilus somnus. AB - In immunoblot analysis, a murine monoclonal antibody (MAb), 27-1, which was produced to an outer membrane protein (OMP) of Haemophilus somnus, showed that a major OMP is heat modifiable, having a molecular mass of 28 kDa when the N lauroylsarcosine-insoluble OMP preparation was solubilized at 60 degrees C and a mass of 37 kDa when the OMP preparation was solubilized at 100 degrees C. The heat-modifiable OMP reacted intensely with convalescent sera obtained from calves with experimental H. somnus pneumonia in immunoblot analysis. Immunoelectron microscopic and antibody absorption studies revealed that the MAb 27-1 epitope was not surface exposed on the intact bacterium. However, a decrease in antibody reactivity to the heat-modifiable OMP in immunoblot analysis after absorption of convalescent serum with intact bacterial cells of H. somnus suggests that a surface-exposed portion of the heat-modifiable OMP is expressed on the intact bacterium. MAb 27-1 reacted with 45 of 45 strains of H. somnus tested in immunoblot analysis. The apparent molecular mass of the antigen varied among strains, and five reactivity patterns demonstrated by MAb 27-1 were observed. MAb 27-1 also reacted with six species in the family Pasteurellaceae, Escherichia coli, and Salmonella dublin, but not with the other eight species of gram negative bacteria. The heat-modifiable OMP of H. somnus showed immunological cross-reactivity with the OmpA protein of E. coli K-12 and significant N-terminal amino acid sequence homology with the OmpA proteins of gram-negative bacteria. We conclude that a major, 37-kDa heat-modifiable OMP of H. somnus, which elicits an antibody response in H. somnus-infected animals, is a common antigen among H. somnus strains tested and is structurally related to the OmpA protein of E. coli. PMID- 8478065 TI - Reactivity of the human antiendotoxin immunoglobulin M monoclonal antibody HA-1A with lipopolysaccharides from rough and smooth gram-negative organisms. AB - Clinical data suggest that the human immunoglobulin M antiendotoxin antibody HA 1A reduced mortality in patients diagnosed with gram-negative bacteremia and bacteremia with shock. Previous studies have demonstrated that HA-1A binds to the lipid A domain of lipopolysaccharide (LPS). The present study evaluated the ability of HA-1A to interact with LPs isolated from various strains of gram negative bacteria by using liquid-phase rate nephelometry and solid-phase immunoblotting assays. HA-1A formed immune complexes in solution with LPSs isolated from both rough and smooth gram-negative organisms. Western blot (immunoblot) analysis of these LPS preparations revealed that HA-1A bound to LPS isolated from rough gram-negative organisms and to a rough LPS-like component present in smooth LPS. HA-1A also bound to LPS-protein complexes found in certain commercial rough LPS preparations. Preincubation of HA-1A with lipid A completely blocked subsequent binding of HA-1A to LPS in both liquid- and solid-phase assay formats, suggesting that the interaction of HA-1A with LPS is through the lipid A domain. Evidence that the binding of HA-1A to LPS was mediated through the antigen-combining (Fv) region of the antibody was provided by the finding that a murine anti-idiotypic antibody to HA-1A inhibited binding. These findings suggested that the broad antiendotoxin reactivity exhibited by HA-1A appeared to be due to the ability of HA-1A to bind to the conserved lipid A moiety of LPSs derived from both smooth- and rough-phenotype gram-negative bacterial strains. PMID- 8478066 TI - Role of flagella in adherence, internalization, and translocation of Campylobacter jejuni in nonpolarized and polarized epithelial cell cultures. AB - Previous studies of Campylobacter jejuni have suggested that flagellin is an adhesin for epithelial cells and that motility is a virulence factor of this bacterium. The role of flagella in the interactions of C. jejuni with nonpolarized and polarized epithelial cells was examined with flagellar mutants. Flagellated, nonmotile (flaA flaB+ Mot-) and nonflagellated, nonmotile (flaA flaB Mot-) mutants of C. jejuni were constructed by in vivo homologous recombination and gene replacement techniques. Both classes of mutants were found to adhere to cells of human epithelial origin (INT 407) equally well; however, on the basis of the percentage of the inoculum internalized, internalization of the flaA flaB Mot mutants was decreased by factors ranging from approximately 30 to 40 compared with the parent. The flaA flaB+ Mot- mutant was internalized by the INT 407 cells at levels six- to sevenfold higher than the flaA flaB Mot- mutants. Both classes of mutants, unlike the parent, were unable to translocate across polarized Caco-2 monolayers. These results indicate that flagella are not involved in C. jejuni adherence to epithelial cells but that they do play a role in internalization. Furthermore, the results suggest that either the motility of C. jejuni or the product of flaA is essential for the bacterium to cross polarized epithelial cell monolayers. PMID- 8478067 TI - Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor. AB - Activation of the complement system is an important part of host resistance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50% of the donors. C. albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production. Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected. Taken together, these results indicate that monocytes respond to C. albicans with an increased production of complement factors. This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF. PMID- 8478068 TI - Molecular cloning, nucleotide sequence, and characterization of lppB, encoding an antigenic 40-kilodalton lipoprotein of Haemophilus somnus. AB - Haemophilus somnus is a facultative intracellular pathogen which causes a wide range of diseases in cattle. To identify putative virulence determinants, a genomic library of H. somnus in Escherichia coli was screened for Congo red binding, a property associated with virulence in pathogenic bacteria, and subsequently with bovine hyperimmune sera raised against H. somnus HS25. A Congo red-binding clone carrying a 1.8-kb DNA insert was found to encode a strongly seroreactive LppB protein with an apparent molecular weight of 40,000. The nucleotide sequence of the entire DNA insert was determined. Two open reading frames coding for polypeptides with calculated molecular weights of 21,893 and 30,721 were identified. The larger open reading frame encoded LppB, while the smaller reading frame encoded a nonseroreactive protein with a relative molecular mass of approximately 18 kDa. The 16 amino-terminal amino acids of the deduced LppB polypeptide showed strong sequence homology to the signal peptide of secreted bacterial proteins, and the sequence Leu-Ala-Ala-Cys at the putative cleavage site corresponds to the consensus cleavage sequence of bacterial lipoproteins. Synthesis of the mature LppB lipoprotein in H. somnus was inhibited by globomycin, a specific inhibitor of signal peptidase II. LppB was localized to the outer membrane of H. somnus. PMID- 8478069 TI - Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. AB - A high-molecular-mass (120- to 128-kDa) Helicobacter pylori antigen has been associated with peptic ulcer disease. We created a bank of 40,000 random chromosomal fragments of H. pylori 84-183 by using lambda ZapII. Screening of this bank in Escherichia coli XL1-Blue with absorbed serum from an H. pylori infected person permitted the isolation and purification of a clone with a 3.5-kb insert. Subcloning of this insert (pMC3) permitted the expression of a recombinant H. pylori protein that had a mass of approximately 96 kDa and that was recognized by the human serum. Sera that were obtained from H. pylori infected persons and that recognized the native 120- to 128-kDa H. pylori antigen recognized the recombinant 96-kDa pMC3 protein to a significantly greater extent than did sera that did not recognize the native H. pylori antigen. All 19 H. pylori isolates producing the 120- to 128-kDa antigen hybridized with pMC3; none of 13 nonproducers did so (P < 0.001). Because all 15 isolates producing the vacuolating cytotoxin hybridized with pMC3, we called the gene cagA (cytotoxin associated gene). Sequence analysis of pMC3 identified an open reading frame of 859 amino acids, without a termination codon. Parallel screening of a lambda gt11 library with human serum revealed positive plaques with identical 0.6-kb inserts and sequences matching the sequence of the downstream region of pMC3. To clone the full-length gene, we used the 0.6-kb fragment as a probe and isolated a clone with a 2.7-kb insert from the lambda ZapII genomic library. Nucleotide sequencing of this insert (pYB 2) revealed a 785-bp sequence that overlapped the downstream region of pMC3. Translation of the complete nucleotide sequence of cagA revealed an open reading frame of 1,181 amino acids yielding a protein of 131,517 daltons. There was no significant homology with any previously reported protein sequence. These findings indicate the cloning and characterization of a high-molecular-mass H. pylori antigen potentially associated with virulence and with cytotoxin production. PMID- 8478070 TI - Establishment of an antitoxoplasma state by stable expression of mouse indoleamine 2,3-dioxygenase. AB - Indoleamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, is inducible by various interferons (IFNs). IDO-mediated tryptophan degradation, but not the formation of IDO-catalyzed tryptophan metabolites, has been suggested as a mechanism for the antiparasitic action of IFN-gamma. To determine whether the IFN gamma-induced IDO alone is sufficient for establishing the antiparasitic state, we constructed a mouse IDO expression plasmid containing a heavy metal-responsive metallothionein promoter and obtained a stable transformant (C6) by transfection of this plasmid into mouse rectal cancer (CMT-93) cells. In the presence of 100 microM ZnSO4, C6 cells yielded a high level of IDO; and after a 2-day culture period, the enzyme induction resulted in complete depletion of tryptophan from the culture medium. Under these conditions, the growth of Toxoplasma gondii in C6 cells infected with the organisms on day 3 after enzyme induction was completely blocked. In the absence of ZnSO4, however, IDO induction was negligible in C6 cells, and T. gondii continued to grow. Furthermore, in a transformant (CC10) carrying an antisense mouse IDO plasmid or in parental CMT-93 cells, IDO was not induced at all even in the presence of 100 microM ZnSO4, and T. gondii continued to grow in these cells as well. These results taken together indicate that complete depletion of tryptophan from the culture by IDO alone is sufficient to establish the antitoxoplasma state in mouse cells. PMID- 8478072 TI - Coordinate regulation of two opaque-phase-specific genes during white-opaque switching in Candida albicans. AB - Cells of Candida albicans WO-1 switch spontaneously and frequently between a white and an opaque CFU. Recently, an opaque-phase-specific cDNA, PEP1, was cloned and was demonstrated to code for a pepsinogen. By using a differential hybridization screen, a second opaque-phase-specific cDNA, Op4, has been isolated and its corresponding gene has been cloned. Op4 is coordinately regulated with PEP1 but resides on a different chromosome. During temperature-induced mass conversion from opaque to white, transcription of PEP1 and Op4 is immediately inhibited by the increase in temperature, but transcription of both genes can be rapidly reestablished by a downshift in temperature prior to phenotypic commitment. However, the capacity to rapidly induce both PEP1 and Op4 is lost coincidentally with the second semisynchronous round of cell division and phenotypic commitment during mass conversion. Op4 shows no significant base or amino acid sequence homology with a known gene or protein, respectively. However, the deduced Op4 protein exhibits several interesting characteristics, including a hydrophobic amino terminus with 26 amino acids, a pI of 10.73 for the last 100 amino acids, two serine repeats adjacent to alanine repeats, and the potential for alpha-helical conformation within the alanine-rich sequences. No genomic reorganization was evident in the proximity of Op4 during transcriptional activation and deactivation accompanying the white-opaque transition. PMID- 8478071 TI - Long-term study of cell-mediated responses to Borrelia burgdorferi in the laboratory mouse. AB - Borrelia burgdorferi infection of disease-susceptible (C3H) and -resistant (BALB) mice resulted in impaired proliferation to both T- and B-cell mitogens up to 30 days after inoculation. Interleukin-2 and -4 production was also impaired, paralleling the T-cell response to concanavalin A. Impaired lymphocyte proliferation could not be attributed to diminished numbers of T or B cells and was found to depend on the lymphoid organ (spleen or lymph node) examined. Prostaglandin production accounted for part of this immune dysfunction. Attempts to assess antigen-specific proliferation to B. burgdorferi were inconsistent, and delayed-type hypersensitivity responses were not detected. Adoptive transfer of T enriched cells from chronically infected donors failed to prevent infection and disease development in recipient C3H mice. The current study emphasizes caution in the study of B. burgdorferi antigen-specific assays and argues against the role of a vigorous T-cell response in Lyme borreliosis in infected laboratory mice. PMID- 8478073 TI - Characterization of kinetics and target proteins for binding of human complement component C3 to the surface-exposed outer membrane of Chlamydia trachomatis serovar L2. AB - In order to characterize the interaction of human complement with Chlamydia trachomatis, flow cytometry was used to quantitate binding of complement component C3 to elementary bodies of C. trachomatis serovar L2 preincubated in fresh serum in the presence or absence of human polyclonal chlamydial antibody. Isolation of each of the complement activation pathways revealed that C3 was activated most effectively by the alternative pathway. The degree of binding by the classical pathway was proportional to the concentration of antibody, but dual pathway-mediated binding was not greater than antibody-independent alternative pathway binding. Electrophoresis and immunoblotting of detergent-extracted outer membrane protein-C3b complexes indicated that the chlamydial major outer membrane protein was the primary cell surface moiety binding C3b in both the presence and absence of specific antibody. Hydroxylamine cleavage of outer membrane protein C3b complexes provided evidence that the majority of C3b is bound to the major outer membrane protein by hydroxyl ester bonds. This result was also unchanged by the presence of specific antibody. An unexpected finding was the apparent binding of anti-C3 antibody to a 40-kDa protein of the chlamydial outer membrane complex, perhaps indicating C3 mimicry on the part of the chlamydial major outer membrane protein. PMID- 8478074 TI - Effects of in vitro and in vivo growth conditions on expression of type 8 capsular polysaccharide by Staphylococcus aureus. AB - Type 8 capsular polysaccharide (CP8) is widely prevalent among clinical isolates of Staphylococcus aureus, but the role that the capsule plays in the pathogenesis of staphylococcal infections is unclear. This study was performed to identify growth conditions that would optimize the production of CP8 and to determine whether enhanced CP8 expression would influence staphylococcal virulence. S. aureus Becker grown in a chemically defined broth medium with < 1 microM ferric nitrate produced up to eightfold more CP8 per milligram of biomass than did bacteria cultivated in the same medium containing 20 microM ferric nitrate. The bacteria produced > 350-fold more cell-associated CP8 per milligram of biomass when grown on the surface of Columbia agar than when grown in Columbia broth. Most of the CP8 produced by broth-grown cells was secreted into the culture medium. S. aureus cultivated on the surface of nitrocellulose membranes floating on Columbia broth produced levels of CP8 similar to those produced by cells grown on Columbia agar. Similarly, bacteria harvested from endocardial vegetations of rabbits infected with S. aureus produced high levels of CP8. These results indicate that staphylococci grown on surfaces, both in vitro and in vivo, produce larger quantities of cell-associated CP8 than those grown in liquid cultures. However, no differences were observed in the 50% lethal dose for mice of strain Becker grown on solid medium (high levels of capsule expression) or in liquid medium (low levels of capsule expression). PMID- 8478075 TI - Immune responses to Streptococcus sobrinus surface protein antigen A expressed by recombinant Salmonella typhimurium. AB - In this study, we used a vaccine strain of Salmonella typhimurium to express antigenic determinants of the SpaA antigen of Streptococcus sobrinus, which is involved in the caries-forming process. We cloned either a single repeat (pYA2901) or three tandem repeats (pYA2905) of the 0.48-kb fragment of the spaA gene, which codes for an important component of the SpaA protein, plus a 1.2-kb minor antigenic determinant and measured the resulting immune responses to SpaA in orally immunized BALB/c mice. The single or triple repeat of the spaA gene fragment was inserted into the Asd+ vector pYA292 and was transformed into the S. typhimurium delta cya delta crp vaccine strain chi 4072 containing delta asd in the chromosome. Female BALB/c mice were then orally immunized with two doses of the S. typhimurium containing either of the two SpaA constructs, and the immune responses to the expressed SpaA protein were assessed. Significant serum immunoglobulin G (IgG) anti-SpaA titers were detected in mice immunized with chi 4072(pYA2905) but not chi 4072(pYA2901). Salivary anti-SpaA IgA titers were minimal and were only detected in mice immunized with S. typhimurium expressing the SpaA encoded by pYA2905. Intestinal anti-SpaA IgA titers, however, were detected in both groups of mice, particularly in mice immunized with chi 4072(pYA2905). An oral booster 26 weeks after the initial series of immunizations resulted in increased serum IgG titers in both chi 4072(pYA2901)- and chi 4072(pYA2905)-immunized animals, particularly in the chi 4072(pYA2905)-immunized animals. No anamnestic IgA response was detected in the saliva following the booster immunization. PMID- 8478076 TI - Preparation, characterization, and immunogenicity of meningococcal lipooligosaccharide-derived oligosaccharide-protein conjugates. AB - A method was developed for coupling carboxylic acid-containing oligosaccharides (OS) to proteins. An OS was isolated from Neisseria meningitidis group A strain A1 lipooligosaccharide (LOS). This LOS has no human glycolipid-like lacto-N neotetraose structure and contains multiple immunotypes, including L8, found in group B and C strains. The carboxylic acid at 2-keto-3-deoxyoctulosonic acid of the OS was linked through adipic acid dihydrazide to tetanus toxoid. The molar ratio of the OS to tetanus toxoid in three conjugates ranged from 11:1 to 19:1. The antigenicity of the OS was conserved in these conjugates, as measured by an enzyme-linked immunosorbent assay (ELISA) and an inhibition ELISA with polyclonal and monoclonal antibodies to A1 LOS. These conjugates induced immunoglobulin G antibodies to A1 LOS in mice and rabbits. The immunogenicity of the conjugates in rabbits was enhanced by use of monophosphoryl lipid A plus trehalose dimycolate as an adjuvant. The resulting rabbit antisera cross-reacted with most of 12 prototype LOSs and with LOSs from two group B disease strains, 44/76 and BB431, in an ELISA and in Western blotting (immunoblotting), which revealed a 3.6-kDa reactive band in these LOSs. The rabbit antisera showed bactericidal activity against homologous strain A1 and heterologous strains 44/76 and BB431. These results indicate that conjugates derived from A1 LOS can induce antibodies against many LOS immunotypes from different organism serogroups, including group B. OS-protein conjugates derived from meningococcal LOSs may therefore be candidate vaccines to prevent meningitis caused by meningococci. PMID- 8478077 TI - Immunological activities of a Candida albicans protein which plays an important role in the survival of the microorganism in the host. AB - A protein with an isoelectric point of 4.3 and a relative molecular mass of 43 kDa (p43) was purified from the supernatants of the cultures of pathogenic Candida albicans but could not be detected in the supernatants of cultures of this fungus with pathogenicity previously attenuated after being repeatedly subcultured in vitro. Treatment of BALB/c and C57BL/6 mice with p43 resulted in (i) marked increases in the numbers of splenic immunoglobulin-secreting plaque forming cells (PFC) with peak responses of immunoglobulin M (IgM) PFC preceding those of IgG PFC, with an isotype restriction pattern of IgG2a > IgG2b > IgG3 > IgG1 > IgM, and (ii) specific immunosuppression of the murine primary immune response against sheep erythrocytes. Immunosuppressive and B-cell mitogenic properties of p43 were quantitatively associated and inversely correlated with susceptibility to C. albicans infection. C57BL/6 mice treated with p43 2 days before inoculation with C. albicans were considerably more susceptible to the fungal infection than untreated mice. The immunobiological and chemical properties of p43 are compared with previously described immunosuppressive and B cell mitogenic proteins produced by bacteria and viruses, and strategies for immunointervention are discussed. PMID- 8478078 TI - Purification of a mycobacterial adhesin for fibronectin. AB - Previous studies have demonstrated that mycobacteria attach to fibronectin (FN). The attachment of mycobacteria to FN is considered to be biologically important in Mycobacterium bovis BCG therapy for superficial bladder cancer, initiation of delayed hypersensitivity to mycobacterial antigens, and the phagocytosis of mycobacteria by epithelial cells. Therefore, we purified the mycobacterial receptor for FN. Culture supernatants from 3-week cultures of Mycobacterium vaccae, which contained proteins that bound FN and inhibited the attachment of both M. vaccae and BCG to FN, were used as a source of receptor. Lyophilized M. vaccae supernatants were reconstituted in 0.02 M bis-Tris (pH 6.0) and applied sequentially to an ACA 54 gel filtration column and a DEAE-Sephacel anion exchange column. A purified inhibitory protein of 55 kDa (p55) was obtained. The purified p55 protein was observed to bind to FN and to inhibit 125I-FN binding to viable BCG in a dose-dependent manner. Polyclonal and monoclonal antibodies to the protein were generated. The resulting polyclonal antiserum blotted a single protein band at 55 kDa in crude M. vaccae supernatants, cross-reacted with a 55 kDa BCG protein by Western blot (immunoblot), and recognized a 55-kDa band that was associated with the BCG cell wall, which is consistent with its function as a FN receptor. A monoclonal immunoglobulin M(lambda) was isolated from mice immunized with purified M. vaccae p55 protein that was not functional in Western blots but inhibited the attachment of viable BCG to FN. These studies demonstrate that a protein or antigenically related proteins with M(r)s of 55,000 function as FN receptors for at least two distinct mycobacteria. PMID- 8478079 TI - Synthetic peptides of human lysosomal cathepsin G with potent antipseudomonal activity. AB - Enzymatically active and inactive (diisopropylfluorophosphate-treated) cathepsin G exerted antibacterial action in vitro against Staphylococcus aureus, whereas only enzymatically active cathepsin G displayed bactericidal action against Pseudomonas aeruginosa. In order to further test the requirement for protease activity for the antipseudomonal action of cathepsin G, synthetic peptides spanning the full-length mature protein were prepared and examined for antibacterial action. Surprisingly, three structurally distinct peptides that correspond to residues 61 to 80, 117 to 136, and 198 to 223 within the full length protein were found to exert potent antipseudomonal action (> 4.5 logs of killing at 500 micrograms/ml) against P. aeruginosa ATCC 27853 and four mucoid clinical isolates. Only the peptide (CG117-136) corresponding to residues 117 to 136 (117-RPGTLCTVAGWGRVSMRRGT-136) within cathepsin G exerted antibacterial action against the gram-positive pathogen S. aureus. The antipseudomonal action of CG117-136 was rapid and could be inhibited either by increasing concentrations of NaCl or by 0.5 mM MgCl2 plus 0.5 mM CaCl2, and these conditions appeared to reduce binding of the peptide to whole bacteria. Variants of peptide CG117-136 lacking either a hydrophobic N-terminal domain or a positively charged C-terminal domain were found to have significantly less antipseudomonal action than CG117 136. The antibacterial capacity of the all-D-enantiomeric form of peptide CG117 136 was found to be identical to that of the all-L-peptide, suggesting that the mechanism of killing does not require the recognition of a target site possessing a chiral center. PMID- 8478080 TI - Sequence divergence in two tandemly located pilin genes of Eikenella corrodens. AB - Eikenella corrodens normally inhabits the human respiratory and gastrointestinal tracts but is frequently the cause of abscesses at various sites. Using the N terminal portion of the Moraxella nonliquefaciens pilin gene as a hybridization probe, we cloned two tandemly located pilin genes of E. corrodens 31745, ecpC and ecpD, and expressed the two pilin genes separately in Escherichia coli. A comparison of the predicted amino acid sequences of E. corrodens 31745 EcpC and EcpD revealed considerable divergence between the sequences of these two pilins and even less similarity to EcpA and EcpB of E. corrodens type strain ATCC 23834. EcpC from E. corrodens 31745 displayed high degrees of homology to the pilins of Neisseria gonorrhoeae and Pseudomonas aeruginosa. EcpD from E. corrodens 31745 showed the highest homologies with the pilin of one of the three P. aeruginosa classes, whereas EcpA and EcpB of strain ATCC 23834 most closely resemble Moraxella bovis pilins. These findings raise interesting questions about potential genetic transfer between different bacterial species, as opposed to convergent evolution. PMID- 8478081 TI - Similar mechanisms of action of defined polysaccharides and lipopolysaccharides: characterization of binding and tumor necrosis factor alpha induction. AB - Little has been reported about the effects of different polysaccharides on cytokine production from human monocytes. In this study, we show that several well-defined polysaccharides, including polymers with different sizes of beta 1-4 linked D-mannuronic acid (poly-M, high-M alginate, and M-blocks) and cellulose oxidized in the C-6 position, induced human monocytes to produce tumor necrosis factor alpha (TNF-alpha). Poly-M was the most efficient polysaccharide tested and, on a weight basis, was approximately as efficient as lipopolysaccharide (LPS) from Escherichia coli. TNF-alpha production was shown to depend strongly on the molecular weights of poly-M and high-M alginate, with maximal TNF-alpha production occurring at molecular weights above 50,000 and 200,000, respectively. G-blocks, alpha 1-4-linked L-guluronic acid polymers that did not induce cytokine production from monocytes, reduced the cytokine production induced by the beta 1 4-linked polyuronic acids and LPS. Furthermore, both G-blocks and LPS were found to inhibit the binding of poly-M to monocytes, as measured by flow cytometry. In addition, we found that the binding of LPS to monocytes was inhibited by G blocks, M-blocks, and poly-M. Our results indicate that beta 1-4-linked polyuronic acids and LPS may stimulate monocytes to produce TNF-alpha by similar mechanisms and may bind to a common receptor. PMID- 8478082 TI - Directional actin polymerization associated with spotted fever group Rickettsia infection of Vero cells. AB - Members of the spotted fever group (SFG) of rickettsiae spread rapidly from cell to cell by an unknown mechanism(s). Staining of Rickettsia rickettsii-infected Vero cells with rhodamine phalloidin demonstrated unique actin filaments associated with one pole of intracellular rickettsiae. F-actin tails greater than 70 microns in length were seen extending from rickettsiae. Treatment of infected cells with chloramphenicol eliminated rickettsia-associated F-actin tails, suggesting that de novo protein synthesis of one or more rickettsial proteins is required for tail formation. Rickettsiae were coated with F-actin as early as 15 min postinfection, and tail formation was detected by 30 min. A survey of virulent and avirulent species within the SFG rickettsiae demonstrated that all formed actin tails. Typhus group rickettsiae, which do not spread directly from cell to cell, lacked F-actin tails entirely or exhibited only very short tails. Transmission electron microscopy demonstrated fibrillar material in close association with R. rickettsii but not Rickettsia prowazekii. Biochemical evidence that actin polymerization plays a role in movement was provided by showing that transit of R. rickettsii from infected cells into the cell culture medium was inhibited by treatment of host cells with cytochalasin D. These data suggest that the cell-to-cell transmission of SFG rickettsiae may be aided by induction of actin polymerization in a fashion similar to that described for Shigella flexneri and Listeria monocytogenes. PMID- 8478083 TI - Analysis of Candida albicans adhesion to salivary mucin. AB - Clearance of Candida albicans from the oral cavity is thought to be mediated via specific receptor-ligand interactions between salivary constituents and the fungus. Since surfaces in the oral cavity are normally coated with a saliva derived pellicle, specific interactions between salivary constituents and C. albicans may also contribute to adhesion of C. albicans to the oral mucosa and dental prostheses. Therefore, the purpose of this study was to identify salivary constituents to which C. albicans is capable of binding. A solid-phase overlay assay was used in which electrophoretically separated rat and human salivary constituents bound to membrane filters were incubated with radiolabelled C. albicans cells. C. albicans adhered to a single salivary component from each host. Correlation of cell-binding activity with specific monoclonal antibody (MAb)-binding activity indicated that the constituent bound by C. albicans in human saliva was low-molecular-weight mucin (MG2) and that in rat saliva was rat submandibular gland (RSMG) mucin. Further studies showed an identical cell hybridization signal and MAb colocalization by using RSMG ductal saliva and an aqueous RSMG extract in the solid-phase overlay assay. Analysis of cell binding to the aqueous extract of RSMG fractionated by anion-exchange chromatography demonstrated that C. albicans binding was restricted to an acidic subfraction of the RSMG extract, which also bound the RSMG mucin-specific MAb. The Candida binding fraction contained predominantly RSMG mucin glycoprotein and also a noncovalently associated, chloroform-extractable material. Furthermore, we identified two strains of C. albicans which differed severalfold in the ability to bind RSMG mucin in the overlay assay. These results suggest that C. albicans binds to only a specific subfraction of RSMG mucin and that the two C. albicans strains tested differ in the ability to bind RSMG mucin subfractions. PMID- 8478084 TI - Evaluation of mixtures of purified Haemophilus influenzae outer membrane proteins in protection against challenge with nontypeable H. influenzae in the chinchilla otitis media model. AB - Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative agents of bacterial otitis media, and no vaccine has been shown to be effective against it. Three outer membrane lipoproteins of NTHi have been investigated extensively and are leading candidates for inclusion in a vaccine against this organism. Hi PAL (P6), recombinant PCP (rPCP), and e (P4) proteins are antigenically conserved among NTHi strains and elicit bactericidal and protective antibodies. A genetic fusion of the rPCP and Hi-PAL proteins has also been reported. Mixtures of these proteins were used for active immunization experiments in the chinchilla model of otitis media. Chinchillas were immunized either with a mixture of all three lipoproteins or with the mixture of rPCP-PAL hybrid plus e protein. When these animals were challenged with a NTHi strain injected directly into the middle ears, no protection from infection or disease, as measured by otoscopy, was observed in either group. However, effusion and inflammation measured by tympanometry were significantly reduced in animals immunized with the three lipoproteins. Animals that had been immunized with either whole NTHi cells or total outer membranes and then challenged with the homologous strain were significantly protected from both infection and disease, as determined by tympanometry and otoscopy. Unlike other animals antisera, chinchilla antisera against the purified proteins had no bactericidal activity against NTHi but did fix complement on the cell surface. Thus, the chinchilla immune responses to mixtures of these lipoproteins differ from the immune responses observed in other animal species. Further evaluation of these proteins for their vaccine potential remains to be done. PMID- 8478085 TI - An approach to development of specific T-lymphocyte lines by use of preprocessed antigens in Plasmodium vinckei vinckei murine malaria. AB - The development of parasite-specific T-cell lines represents one approach to the potential identification of relevant immunogens in erythrocytic malarial infection. However, the use of parasitized-erythrocyte lysates as antigens inhibits the proliferation of T cells. To circumvent this problem, we preincubated antigen-presenting cells (APCs) from spleens of malaria-naive, BALB/c mice with a Plasmodium vinckei vinckei (hereafter referred to as P. vinckei)-parasitized erythrocyte lysate. APCs were subsequently irradiated and washed prior to being incubated with T lymphocytes from P. vinckei-immune, histocompatible mice. After 8 to 10 cycles of antigenic stimulation and rest, two T-cell lines were analyzed. Both lines were predominantly CD4+. Proliferation assays demonstrated marked lymphocyte blastogenesis to syngeneic but not allogeneic APCs that had preprocessed malarial antigen. Antigen incubated directly with T cells and nonpulsed APCs in vitro did not result in T-cell proliferation. Assays of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon were compatible with one cell line being predominantly TH1 and the other being TH2. Thus, APCs that have preprocessed malarial antigen and are free of extraneous parasite material induce highly reactive, antigen-specific, major histocompatibility complex-restricted T-cell lines that functionally appear capable of inducing humoral and/or cell-mediated immunity. PMID- 8478087 TI - Bacteria induce release of platelet-activating factor (PAF) from polymorphonuclear neutrophil granulocytes: possible role for PAF in pathogenesis of experimentally induced bacterial pneumonia. AB - The role of platelet-activating factor (PAF) as mediator of the endotoxin shock and endotoxin-dependent tissue injury has been examined. The ability of opsonized bacteria to stimulate the release of PAF from human polymorphonuclear neutrophil granulocytes was evaluated by measuring both the activity and the amount of the mediator released in the supernatant of the cell-bacteria reaction in vitro. There was no significant difference between gram-positive and gram-negative bacteria in the ability to release PAF from neutrophils. However, preincubation of the cells with the specific PAF receptor antagonist WEB 2170 decreased release of PAF from the cells. Furthermore, a possible protective effect of the PAF antagonist was examined during experimentally induced pneumonia with Klebsiella pneumoniae in NMRI mice. Oral treatment of mice with WEB 2170, followed by infection with the microorganisms, resulted in a considerable increase in the animals' survival (53 to 73%) compared with the control group (40%); this increase corresponded with a decrease in the CFU per gram of lung tissue. These findings indicate an important role of PAF in the pathogenesis of pneumonia in mice. PMID- 8478086 TI - Protective salivary immunoglobulin A responses against Streptococcus mutans infection after intranasal immunization with S. mutans antigen I/II coupled to the B subunit of cholera toxin. AB - The B subunit of cholera toxin (CTB) has been shown to augment mucosal responses to microbial virulence antigens, including those of Streptococcus mutans, which is the principal etiologic agent of dental caries. In the present study, the surface fibrillar protein antigen of S. mutans, antigen I/II (Ag I/II), was chemically coupled to CTB (Ag I/II-CTB), and the conjugate was examined for its effectiveness in inducing salivary immune responses protective against S. mutans infection. Weanling Fischer rats were given Ag I/II-CTB (50 micrograms) by the intranasal route and then orally infected with a virulent strain of S. mutans. Gnotobiotic or conventional rats were given two or three additional immunizations, respectively, at about 2-week intervals. One week after each immunization, individual serum, saliva, and fecal samples were collected and stored frozen until assayed for antibody activity to Ag I/II and cholera toxin (CT) by an enzyme-linked immunosorbent assay. The rats were sacrificed 1 week after the last immunization, when mandibles were also collected from individual rats for assessment of S. mutans levels in plaque and caries activity. Rats immunized only or both immunized and infected showed a salivary immunoglobulin A (IgA) anti-Ag I/II response which reached significantly (P < 0.05) higher levels than those seen in nonimmunized, infected controls. A salivary IgA anti-Ag I/II response was also seen in rats infected only with S. mutans. Essentially no salivary antibody activity to CT was detected. Some serum anti-Ag I/II and anti CT responses were seen in immunized animals. Serum IgG anti-Ag I/II responses were seen in immunized, infected rats and also in infected-only rats, suggesting that the responses were a result of infection with S. mutans. The immunized and infected rats had significantly (P < 0.05) lower levels of S. mutans in plaque and lower caries activity than nonimmunized, infected rats. These results indicated that intranasal immunization of rats with Ag I/II-CTB induced a protective salivary immune response which was associated with a reduction in S. mutans colonization and S. mutans-induced dental caries. PMID- 8478088 TI - Coaggregation of Prevotella intermedia with oral Actinomyces species. AB - Five strains of Prevotella intermedia were examined for their ability to coaggregate with various gram-positive and gram-negative species of oral bacteria. Two of the P. intermedia strains coaggregated with selected Actinomyces species, P. intermedia 27 with Actinomyces viscosus T14V and Actinomyces naeslundii ATCC 12104, PK606, PK984, and PK947, and P. intermedia 113 with Actinomyces odontolyticus WVU 1546 and Actinomyces israelii WVU 838. Exposure of both Prevotella strains but not the Actinomyces strains to heat, trypsin, or proteinase K abolished most coaggregations. All pairs were disaggregated by the addition of sodium dodecyl sulfate, but only those coaggregations involving P. intermedia 113 were reversed by the addition of 2.0 M urea. P. intermedia 27 was sensitive to periodate oxidation, whereas the partner strains were stable to this treatment. Most coaggregations occurred in the presence of saliva; however, reactions involving P. intermedia 27 were not as strong as those of buffer suspended cells. Treatment of both P. intermedia 113 coaggregations pairs with proteinase K and the results obtained from suspensions of these pairs in saliva suggest that different surface molecules of this P. intermedia strain may mediate each of these coaggregations. These data suggest that all of these coaggregations involve either a protein or glycoprotein on the Prevotella strain, which may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces strain. PMID- 8478089 TI - Rickettsial stimulation of endothelial platelet-activating factor synthesis. AB - Endothelial cells (EC) synthesize platelet-activating factor (PAF) when activated by agents such as ATP or thrombin, and PAF production occurs as a consequence of endothelial phospholipase A activity. Because interactions between Rickettsia prowazekii and a variety of host cells result in the expression of phospholipase A activity, we assessed the relative abilities of uninfected and rickettsia infected EC to synthesize PAF. Endothelial cells were infected with rickettsiae and examined at 24-h intervals for rickettsial multiplication, EC viability, and PAF synthesis. By 24 h postinfection, 80% of the EC were infected with an average of 10.6 rickettsiae per cell; by 72 h, the rickettsiae were too numerous to count and the numbers of viable EC began to decrease. Both rickettsia-infected and sham treated EC synthesized PAF when stimulated with either thrombin or ATP, but rickettsia-infected EC synthesized about three times as much PAF in response to cell activation as did their uninfected counterparts. Additionally, unlike their uninfected counterparts, rickettsia-infected EC synthesized significant amounts of PAF in the absence of cell activation; rickettsia-infected EC synthesized as much PAF in the absence of activation as did uninfected EC in response to ATP. In each case, essentially all of the newly synthesized PAF remained with the cell pellet. Finally, EC incubated with high numbers of rickettsiae (1,000 rickettsiae per EC) for 30 min synthesized more PAF when activated with ATP than did their sham-treated activated counterparts. PMID- 8478090 TI - Heterogeneity of the purified extracellular aspartyl proteinase from Candida albicans: characterization with monoclonal antibodies and N-terminal amino acid sequence analysis. AB - Three dominant proteins (41, 48, and 49 kDa) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in purified preparations of the extracellular aspartyl proteinase (AP) of Candida albicans. All three proteins bound to the specific carboxyl proteinase ligand, pepstatin A, and were associated with maximum AP activity. The N-terminal amino acid sequence for the 48- and 49-kDa proteins matched that reported by others for AP, whereas the sequence for the 41-kDa protein was unique and was not homologous to any known protein. Time course studies demonstrated the simultaneous presence of all three proteins, supporting evidence that the 41- and 48-kDa proteins were not breakdown products of AP. Previous studies did not detect carbohydrate in SDS polyacrylamide gels of purified AP preparations stained with periodic acid and silver, making glycosylation an unlikely explanation for the observed differences in the molecular masses of the proteins. Some monoclonal antibodies directed against the 49-kDa protein reacted with the 41- and 48-kDa proteins, indicating cross-reactive epitopes. Other monoclonal antibodies, however, reacted only with the 49-kDa protein. We conclude that three pepstatin A-binding proteins occur in purified AP preparations: two have the same amino acid N terminus as that reported for AP, whereas the third has a unique sequence. All three proteins should be considered when undertaking studies to determine the role of AP in candidal pathogenesis or when preparing specific antibodies for antigen capture assays. PMID- 8478091 TI - A mouse model of Chlamydia pneumoniae strain TWAR pneumonitis. AB - Chlamydia pneumoniae is a common cause of acute respiratory infections in humans. We evaluated mice as experimental animals for C. pneumoniae. Intranasal inoculation of Swiss Webster mice with C. pneumoniae induced a prolonged course of lung infection, as demonstrated by reisolation of organisms from lungs (at 42 days) and persistence of lung pathology (> 60 days). The lung pathology was characterized by patchy interstitial pneumonitis with predominantly polymorphonuclear leukocyte infiltration in the early and mononuclear cell infiltration in the later stages of infection. Inoculated mice developed serum immunoglobulin G antibody responses and partial resistance against rechallenge inoculation. The other mouse strains tested, Icr, BALB/cAnN, C57BL/6N, C3H/HeN, and B6C3F1, were shown to be susceptible to C. pneumoniae. The mouse model should be useful for investigating the immunopathogenesis of C. pneumoniae infections. PMID- 8478092 TI - Protective immunity induced in Aotus monkeys by a recombinant SERA protein of Plasmodium falciparum: adjuvant effects on induction of protective immunity. AB - We report the results of vaccination trial 2 of Panamanian Aotus monkeys with a recombinant blood-stage antigen, SERA 1, of the malaria parasite Plasmodium falciparum. Monkeys were immunized with SERA 1, a 262-amino-acid fragment (amino acids 24 to 285) of the 989-amino-acid SERA protein produced by the Honduras 1 strain of the parasite. Immunization mixtures contained 100 micrograms of recombinant SERA 1 protein per dose mixed with one of five different adjuvants. The protein mixed with either Freund's adjuvant or MF75.2 adjuvant stimulated protective immunity. When other P. falciparum antigens were included in the SERA 1-Freund's adjuvant mixture, no protective immunity was observed, although high anti-SERA 1 antibody titers were produced. Three other adjuvants mixed with SERA 1 failed to induce a protective immune response. These results, their relationship to those reported previously in the first vaccination trial (trial 1), and their relationships to the quantitative measurement of anti-SERA 1 antibodies in enzyme-linked immunosorbent assays provided insights into the induction of a protective immune response in vaccinated monkeys. PMID- 8478093 TI - Protective immunity induced in Aotus monkeys by a recombinant SERA protein of Plasmodium falciparum: further studies using SERA 1 and MF75.2 adjuvant. AB - We describe the third of three vaccination trials of Panamanian Aotus monkeys with a recombinant blood-stage antigen derived from the malaria parasite Plasmodium falciparum. Immunization was performed with an N-terminal region of the SERA antigen (serine repeat antigen protein), SERA 1, that contains a 262 amino-acid fragment including amino acids 24 to 285 of the 989-amino-acid SERA protein. Vaccinations were carried out with the recombinant protein mixed with either Freund's, MF75.2, or MF59.2 adjuvant. A control group that did not receive SERA 1 but only MF75.2 adjuvant was included. Monkeys vaccinated with the antigen MF59.2 mixture produced low anti-SERA 1 titers and were not protected. Monkeys vaccinated with antigen and Freund's adjuvant had, in general, a higher average anti-SERA 1 titer (107,278) than did monkeys immunized with SERA 1 and MF75.2 (40, 143), yet monkeys in both groups were well protected. Monkeys that received only MF75.2 developed neither detectable anti-SERA 1 nor anti-P. falciparum antibodies prior to or 10 days after parasite challenge, yet were apparently protected against infection. Monkeys vaccinated with either SERA 1 and Freund's, SERA 1 and MF75.2, or MF75.2 alone and that had been challenged but did not develop a countable parasitemia were treated with a curative dose of mefloquine 100 days after parasite challenge and then rechallenged 40 days later. None of the five rechallenged monkeys that had originally received SERA 1 and Freund's developed a countable parasitemia. Only one of five rechallenged monkeys that originally received SERA 1 and MF75.2 developed a high countable parasitemia, while two animals developed a barely countable parasitemia. Four of the rechallenged monkeys that had originally received only MF75.2 developed a moderate to high countable parasitemia. The results indicate that vaccination with SERA 1 and either Freund's or MF75.2 adjuvant provides protection and vaccination with MF75.2 alone can provide a temporary protection unrelated to the induction of anti-SERA 1 or antimalarial antibodies. PMID- 8478094 TI - Immunogenicity of Vibrio vulnificus capsular polysaccharides and polysaccharide protein conjugates. AB - Opaque colony morphology has been correlated to Vibrio vulnificus virulence. However, the number of capsular serotypes expressed by virulent isolates is unknown. In an effort to produce anticapsule sera, capsular polysaccharide (CPS) from three opaque V. vulnificus strains was purified and characterized. Purified CPSs were acidic and contained considerable amounts of hexosamine and trace quantities of protein and nucleic acid. CPS purified from strain C7184 was poorly immunogenic for rabbits and mice, since repeated injection produced little detectable anticapsular antibody. To improve immunogenicity, CPS-protein conjugates were prepared from adipic acid hydrazide derivatives of CPS purified from each strain and carbodiimide as a coupling reagent. The immunogenicity of C7184 CPS was enhanced by conjugation to keyhole limpet hemocyanin, since injection into mice elicited production of anticapsular antibodies, the level of which was dependent on the dose and time since initial immunization. Injection of rabbits with CPS-protein conjugates also produced anticapsular antibodies. Staphylococcus aureus cells armed with each of the three anticapsular antibodies coagglutinated only the homologous opaque strain, indicating the existence of at least three capsular types. Further screening of 32 opaque and translucent V. vulnificus isolates revealed only three cross-reacting strains. These results suggest the presence of numerous V. vulnificus capsular types. PMID- 8478096 TI - Evidence for two cell division cycle (CDC) genes that govern yeast bud emergence in the pathogenic fungus Wangiella dermatitidis. AB - Strains Mc2 and Mc3 are morphological mutants of the melanized, pathogenic fungus Wangiella dermatitidis. These strains possess temperature-sensitive (ts) mutations designated mcm2 and mcm3, respectively. At the restrictive temperature (37 degrees C), uninucleate yeast cells of strains Mc2 and Mc3 cease budding and initiate an isotropic mode of cellular development, which is reflected in the formation of a multicellular and multinucleate morphology. Because W. dermatitidis either lacks or has an undiscovered sexual cycle, parasexual methods of analysis were used to confirm that mcm2 and mcm3 define separate bud emergence control genes in the wild-type strain. Spheroplasts of albino auxotrophs derived from strains Mc2 and Mc3 were fused and then regenerated on minimal medium. The resulting fusion products grew as darkly pigmented, prototrophic colonies. When incubated at 37 degrees C, all fusion products exhibited polarized growth predominantly as uninucleate, budding yeasts and less frequently as pseudohyphae and moniliform hyphae. Subsequent analysis of cultures derived from albino, ts segregants, which were induced from fusion products by using methyl benzimidazole 2-yl-carbamate, revealed three types of cell populations. Two resembled those expressed by strain Mc2 or Mc3. The third consisted of a cell population unlike the former, suggesting the presence of both ts mutations in all cells. These results imply that yeast development in the fusion products resulted from intergenic complementation of mcm2 and mcm3, i.e., they are nonallelic. Because mcm2 and mcm3 are equivalent to certain cdc lesions in the yeast Saccharomyces cerevisiae, we have renamed the analogous genes defined by the mutations in W. dermatitidis as CDC1 and CDC2. To our knowledge, these are the first CDC genes identified in a dematiaceous fungus. PMID- 8478095 TI - Staphylococcal enterotoxin type A internal deletion mutants: serological activity and induction of T-cell proliferation. AB - Previous findings indicate that the N-terminal region of staphylococcal enterotoxin type A (SEA) is required for its ability to induce T-cell proliferation. To better localize internal peptides of SEA that are important for induction of murine T-cell proliferation, SEA mutants that had internal deletions in their N-terminal third were constructed. A series of unique restriction enzyme sites were first engineered into sea; only one of these changes resulted in an amino acid substitution (the aspartic acid residue at position 60 of mature SEA was changed to a glycine [D60G]). Because the D60G substitution had no discernible effect on serological or biological activity, the sea allele encoding this mutant SEA was used to construct a panel of mutant SEAs lacking residues 3 to 17, 19 to 23, 24 to 28, 29 to 49, 50 to 55, 56 to 59, 61 to 73, 68 to 74, or 74 to 85. Recombinant plasmids with the desired mutations were constructed in Escherichia coli and transferred to Staphylococcus aureus. Staphylococcal culture supernatants containing the mutant SEAs were examined. Western immunoblot analysis with polyclonal anti-SEA antiserum revealed that each of the recombinant S. aureus strains produced a mutant SEA of the predicted size. All the mutant SEAs exhibited increased sensitivity to monkey stomach lavage fluid in vitro, which is consistent with these mutants having conformations unlike that of wild type SEA or the SEA D60G mutant. In general, deletion of internal peptides had a deleterious effect on the ability to induce T-cell proliferation; only SEA mutants lacking either residues 3 to 17 or 56 to 59 consistently produced a statistically significant increase in the incorporation of [3H]thymidine. In the course of this work, two monoclonal antibodies that had different requirements for binding to SEA in Western blots were identified. The epitope for one monoclonal antibody was contained within residues 108 to 230 of mature SEA. Binding of the other monoclonal antibody to SEA appeared to be dependent on the conformation of SEA. PMID- 8478097 TI - Oral immunization with Toxoplasma gondii antigens in association with cholera toxin induces enhanced protective and cell-mediated immunity in C57BL/6 mice. AB - Following oral immunization of C57BL/6 mice with a Toxoplasma gondii sonicate (TSo) in association with either cholera toxin (CT) or CT B subunit, the T. gondii-specific in vitro proliferation of splenic T lymphocytes was determined. Cytokines produced by these T cells were then characterized. After oral challenge with T. gondii 76K cysts, the percentage of cumulative survival was assessed, as was the number of brain cysts in the mice which survived. The TSo-specific proliferation of splenic T lymphocytes was greatly enhanced by the use of CT, whereas CT B subunit alone did not lead to amplification of splenic T-cell proliferation. The use of CT was associated with an increase of interleukin-2 (IL 2) and gamma interferon synthesis by TSo-stimulated splenic T cells, whereas no enhancement of IL-5 and IL-6 production was observed. IL-4 was not detected. A significant protection of mice immunized orally with TSo plus CT was observed in comparison with those immunized with TSo alone. This protection was associated with a large decrease in the number of brain cysts compared with the number found in naive mice infected orally with a sublethal dose of T. gondii 76K cysts. Further studies, using well-defined T. gondii proteins which are known to induce both mucosal and systemic immune responses, are needed to confirm the value of CT in the enhancement of protection against oral toxoplasmosis. PMID- 8478098 TI - Molecular characterization of a leukotoxin gene from a Pasteurella haemolytica like organism, encoding a new member of the RTX toxin family. AB - A Pasteurella haemolytica-like organism, a new species of bacterium isolated from piglets with diarrhea, secretes a leukotoxin into the culture media. Western blot (immunoblot) analysis indicated that this leukotoxin cross-reacted with antileukotoxin antibody derived from cattle immunized with P. haemolytica. Five overlapping recombinant bacteriophages carrying the gene for this 105-kDa polypeptide were identified with a DNA probe containing sequences from the P. haemolytica lktCA genes from a P. haemolytica-like organism strain 5943 genomic library. Sequence analysis of a region of the cloned DNA revealed two open reading frames encoding proteins with predicted masses of 19.4 and 101.6 kDa. These genes, which we designate pllktC (P. haemolytica-like organism leukotoxin C gene) and pllktA (A gene), respectively, are similar in sequence to the RTX (repeat of toxin) toxin family. The structure of the 101.6-kDa protein derived from the DNA sequence shows three transmembrane domains in the N-terminal part of the protein, 13 glycine-rich repeat domains in the second half of the protein, and a hydrophobic C-terminal part. pllktC and pllktA are strongly homologous to P. haemolytica lktC and lktA genes. However, this leukotoxin kills both BL-3 and pig leukocytes and is not hemolytic. PMID- 8478099 TI - Nucleotide sequence analysis of the gtfT gene from Streptococcus sobrinus OMZ176. AB - The gtfT gene and its upstream region isolated from the Streptococcus sobrinus OMZ176 chromosomal DNA were sequenced. The gtfT gene was preceded by a potential Shine-Dalgarno sequence. The gtfT gene product, glucosyltransferase (GTF), displays a typical gram-positive bacterial signal peptide sequence and both an active site peptide sequence and carboxy-terminal repeats typical of GTFs. The signal sequence is similar to those of other known GTF proteins. The putative active-site peptide sequence of this enzyme was DGIRVDAVD, which was different by one amino acid from the active-site peptide sequence derived from two different types of the S. sobrinus GTFs reported previously (G. Mooser, S. A. Hefta, R. J. Paxton, J. E. Shively, and T. D. Lee, J. Biol. Chem. 266:8916-8922, 1991). The gtfT gene product has three repeated sequences of 51 to 52 amino acids and a partial repeat of 18 amino acids. Another open reading frame (ORF) was detected in the region immediately upstream of the gtfT gene. The upstream ORF showed substantial DNA homology with the gtfS gene isolated from Streptococcus downei MFe28. The inferred amino acid sequence of the upstream ORF has four repeating units and has extensive homology with the repeated peptides coded by the S. downei gtfS gene. These results suggested that the gtfT gene was a typical gtf gene isolated from the mutans streptococci and that the two gtf genes were located in tandem on the chromosomal DNA of S. sobrinus OMZ176. PMID- 8478100 TI - Borrelia burgdorferi infection and immunity in mice deficient in the fifth component of complement. AB - When immunocompetent mice are inoculated with Borrelia burgdorferi, they develop acute arthritis and carditis that undergo spontaneous regression despite the persistence of infection. Specific T- and/or B-cell immunity appears to be necessary for resolution of disease manifestations. Humoral immune responses to B. burgdorferi are also important in prevention of B. burgdorferi infection, in that passive transfer of immune sera or protective monoclonal antibodies prevents the spirochete from establishing infection. It has previously been suggested that complement is necessary for effective antibody-mediated host responses against B. burgdorferi. To investigate the role of complement in the pathogenesis and prevention of Lyme disease, we compared the responses to B. burgdorferi challenge inoculation of mice genetically deficient in the fifth component of complement (C5) with those of C5-sufficient mice. All C5-deficient strains tested were susceptible to B. burgdorferi infection, and disease manifestations underwent regression in a similar time-course to those of complement-sufficient mice. Moreover, passive immunization of C5-deficient mice with either immune rabbit sera or neutralizing monoclonal antibody protected them from challenge infection. These results demonstrate that the expression of Lyme disease is not altered in mice deficient in C5 and that C5-mediated complement activation is not necessary for antibody-mediated protection from infection. PMID- 8478101 TI - Dietary vitamin D affects cell-mediated hypersensitivity but not resistance to experimental pulmonary tuberculosis in guinea pigs. AB - Outbred, Hartley strain guinea pigs were fed purified diets varying only in their levels of vitamin D. The amounts of vitamin D in the diets were adjusted to represent 0, 25, 50, 100, or 200% of the recommended level (1,180 IU/kg of body weight) for guinea pigs. In some experiments, half of the animals in each diet group were vaccinated with Mycobacterium bovis BCG vaccine at the time the diets were introduced. Six weeks later, all guinea pigs were infected by the respiratory route with a low dose of virulent M. tuberculosis H37Rv. Vitamin D deficient animals exhibited marked reductions in levels of the major vitamin D metabolite, 25-hydroxyvitamin D3, in plasma. Altered vitamin D intake was accompanied by changes in antigen (purified protein derivative)-induced, cell mediated immune responses both in vivo (tuberculin hypersensitivity) and in vitro (lymphoproliferation). Dermal tuberculin reactivity developed more slowly in vitamin D-deficient guinea pigs but eventually achieved normal levels. The proliferation of splenocytes cultured with purified protein derivative was suppressed by both deficiency and excess of dietary vitamin D. Vitamin D status did not affect the abilities of naive guinea pigs to control primary, pulmonary tuberculosis, nor did it influence the protective efficacy of BCG vaccination. We conclude that changes in dietary vitamin D are associated with alterations in some cellular immune functions but may not be an important determinant of disease outcome in pulmonary tuberculosis, as has been suggested previously. PMID- 8478102 TI - Abrogation of suppression of delayed hypersensitivity induced by Candida albicans derived mannan by treatment with monophosphoryl lipid A. AB - Monophosphoryl lipid A (MLA), derived either from Salmonella minnesota or Salmonella typhimurium, was tested for its ability to alter Candida albicans mannan (MAN)-specific suppression. Since we showed previously that naive mice injected intravenously (i.v.) with MAN developed suppressor T cells capable of down-regulating delayed-type hypersensitivity when transferred to immunized recipients, MLA was tested for its ability to influence suppressor activity in the donors of suppressor cells. T-lymphocyte-enriched suspensions from donor mice treated with MLA, especially that derived from S. typhimurium, 2 or 3 days after the injection of MAN lost the ability to suppress delayed-type hypersensitivity when transferred to immunized mice. Transferable suppressor activity was reduced but not always completely abrogated when donor animals were treated with MLA 1 day following the administration of MAN. In several experiments, S. minnesota MLA also abrogated activity, but it was not effective in other transfer experiments. In a different type of experiment, MLA was given to immunized mice which had been suppressed directly with MAN. Mice were immunized, either by the introduction of C. albicans intragastrically followed by inoculation intradermally (i.d.) or by two i.d. inoculations, and MAN-specific suppressor cells were induced in such animals by the i.v. injection of MAN 1 day before the first or second i.d. inoculation in animals given intragastric plus i.d. inoculations and those given two i.d. inoculations, respectively. MLA was administered to such mice prior to the i.v. injection of MAN, on the same day, or 1 to 4 days thereafter. S. typhimurium MLA, especially when given to mice 2 days following the administration of MAN, caused a partial abrogation of suppressor activity. Overall, however, MLA, at 5 to 100 micrograms, had variable and minimal effects on suppressor activity in immunized mice suppressed by the i.v. administration of MAN. In summary, MLA is clearly capable of abrogating MAN-induced suppression when given to nonimmunized animals in which MAN-specific suppressor cells had been induced, but its efficacy in immunized animals suppressed by the i.v. administration of MAN was marginal. PMID- 8478103 TI - Influence of some bacterial and host factors on colonization and invasiveness of Escherichia coli K1 in neonatal rats. AB - Of 209 healthy infants examined, 44 (21.1%) carried Escherichia coli K1 in their feces. Of these 44 isolates, 36 (81.8%) were attributed to 10 different known clonal groups of E. coli K1 and 4 isolates represented unknown types. The influence of mannose-resistant (MR) adhesins, aerobactin production, and resistance to serum on colonization and invasiveness of E. coli K1 in orally infected inbred LEW baby rats was investigated. Strains expressing MR adhesins had significantly higher colonization and invasion rates than non-MR strains did. Mixed-infection experiments of LEW rats revealed interactions between different types of E. coli K1 strains affecting colonization and invasion rats. P fimbriated strains appeared to have a selective advantage for colonization. The bacteremic potentials of different E. coli K1 strains could not be associated with their resistance to sera from LEW rats free of members of the family Enterobacteriaceae. No differences in virulence between fecal E. coli K1 isolates and clinical isolates from diseased humans were found. An influence of the major histocompatibility complex on host susceptibility to invasive E. coli K1 was indicated by comparing the parental LEW rat strain with different congenic LEW strains (RT1). PMID- 8478104 TI - Sequence and immunological characterization of a serine-rich antigen from Mycobacterium leprae. AB - Sera from lepromatous leprosy patients were used to screen a Mycobacterium leprae lambda gt11 library. Three positive plaques were picked, and lysogens were constructed. Immunoblot analysis showed that all of the lysogens expressed an apparently identical beta-galactosidase fusion protein which reacted strongly with the sera. The 1.7-kbp insert from one clone was subcloned into the lacZ gene in pUR290; sequence analysis of the end fused to lacZ revealed an open reading frame with no significant homology to previously published sequences. The insert was used to screen an M. leprae cosmid library, and five clones were isolated. The insert was also found to hybridize to clones expressing the M. leprae antigen which had previously been designated class III and 25L. A 1.8-kbp HindIII fragment was subcloned from one of the cosmids and sequenced. The sequence revealed a 1,227-bp open reading frame, encoding a 408-amino-acid protein with a predicted molecular mass of 42,466 Da. The protein contains amino- and carboxy terminal hydrophobic domains and a hydrophilic central domain; the amino-terminal domain shows some homology to a 51-kDa hypothetical antigen of Mycobacterium tuberculosis, while the hydrophilic region contains a high proportion of serine residues, and we have therefore designated the protein serine-rich antigen (Sra). Some repeated motifs are present in the protein, but their significance is unknown. Seventy-eight percent of serum samples from multibacillary leprosy patients and 68% of serum samples from paucibacillary leprosy patients recognized the fusion protein, showing that this is a major M. leprae antigen. In contrast, all serum samples from endemic controls were negative, while 26% of serum samples from tuberculosis patients were weakly positive. PMID- 8478105 TI - Listeria monocytogenes-induced gamma interferon secretion by intestinal intraepithelial gamma/delta T lymphocytes. AB - gamma/delta T cells represent a major proportion of intestinal intraepithelial lymphocytes (IEL), and it has been suggested that these IEL serve as a first immune barrier against microbial invasion and that they do so by destroying infected epithelial cells. In the present study, we confirm that both alpha/beta and gamma/delta IEL from naive mice express potent cytotoxicity and produce gamma interferon (IFN-gamma) after T-cell receptor (TCR) engagement by specific monoclonal antibodies (MAb). Intraperitoneal administration of the anti gamma/delta TCR MAb GL3 caused downregulation of the gamma/delta TCR in IEL, and IEL from gamma/delta TCR-modulated mice failed to express cytotoxic activity and to secrete IFN-gamma after gamma/delta TCR engagement. In contrast, alpha/beta IEL from such mice were still cytolytic and secreted IFN-gamma. Mice were infected orally with virulent Listeria monocytogenes at doses which caused bacterial invasion through the intestinal epithelia. Although alpha/beta and gamma/delta IEL from these mice expressed high cytolytic activities in antibody redirected killer assays, target cells pulsed with listerial antigens were not lysed. In contrast, IFN-gamma secretion by IEL from L. monocytogenes-infected mice was induced not only by anti-TCR MAb but also by target cells pulsed with listerial antigens, whereas irrelevant antigens, including heat shock protein 60, did not induce IFN-gamma secretion. Furthermore, the number of IFN-gamma secreting IEL, as assessed by the enzyme-linked immunospot technique, was increased during listeriosis. gamma/delta TCR modulation by GL3 administration abrogated antigen-induced IFN-gamma secretion by IEL from infected mice. These findings suggest that L. monocytogenes induced IFN-gamma secretion by gamma/delta IEL from mice suffering from intestinal L. monocytogenes infection and invasion. Thus, the data provide evidence for a role of IFN-gamma-secreting IEL in local resistance against listeriosis and perhaps other food-borne diseases. PMID- 8478106 TI - Immune response of the female rat genital tract after oral and local immunization with keyhole limpet hemocyanin conjugated to the cholera toxin B subunit. AB - The immune response of the female rat genital tract was evaluated with Lewis rats given primary and secondary immunizations with keyhole limpet hemocyanin (KLH) alone or coupled to the cholera toxin (CT) B subunit (CTB) by the oral or intravaginal-uterine route or a combination of routes. CT (2 to 5 micrograms) was administered as an adjuvant with the KLH-CTB conjugate. While a significant mucosal immunoglobulin A (IgA) response was induced by KLH, there were no significant differences among the immunized groups in the levels of IgA antibodies in salivary gland, gut, vaginal, and uterine secretions, with the exception that rats immunized only orally with the KLH-CTB conjugate lacked a detectable vaginal response. Levels of IgA antibodies to CT, however, were significantly increased in genital tract secretions of rats immunized locally versus orally with the KLH-CTB conjugate. Antibody activity of the IgG isotype against both KLH and CT was significantly elevated in genital tract secretions of rats immunized with KLH-CTB by the oral or intravaginal-uterine route and given genital tract boosters, in comparison with the results for the other groups. IgM antibody titers were generally negligible in the different secretions. An enzyme linked spot-forming assay revealed IgA and IgG antibody-secreting cells in salivary gland and uterine tissues. A highly significant correlation between the numbers of antibody-secreting cells and antibody titers existed for uterine IgG but not IgA responses to KLH among the different groups of rats. In conclusion, a vigorous local immune response was induced after immunization of the female rat reproductive tract alone or in combination with peroral challenge with the KLH CTB conjugate. PMID- 8478107 TI - An aromatic-dependent mutant of the fish pathogen Aeromonas salmonicida is attenuated in fish and is effective as a live vaccine against the salmonid disease furunculosis. AB - Aeromonas salmonicida is the etiological agent of furunculosis in salmonid fish. The disease is responsible for severe economic losses in intensively cultured salmon and trout. Bacterin vaccines provide inadequate protection against infection. We have constructed an aromatic-dependent mutant of A. salmonicida in order to investigate the possibility of an effective live-attenuated vaccine. The aroA gene of A. salmonicida was cloned in Escherichia coli, and the nucleotide sequence was determined. The codon usage pattern of aroA was found to be quite distinct from that of the vapA gene coding for the surface array protein layer (A layer). The aroA gene was inactivated by inserting a fragment expressing kanamycin resistance within the coding sequence. The aroA::Kar mutation was introduced into the chromosome of virulent A. salmonicida 644Rb and 640V2 by allele replacement by using a suicide plasmid delivery system. The aroA mutation did not revert at a detectable frequency (< 10(-11). The mutation resulted in attenuation when bacteria were injected intramuscularly into Atlantic salmon (Salmo salar L.). Introduction of the wild-type aroA gene into the A. salmonicida mutants on a broad-host-range plasmid restored virulence. A. salmonicida mutant 644Rb aroA::Kar persisted in the kidney of brown trout (Salmo trutta L.) for 12 days at 10 degrees C. Vaccination of brown trout with 10(7) CFU of A. salmonicida 644Rb aroA by intraperitoneal injection resulted in a 253-fold increase in the 50% lethal dose (LD50) compared with unvaccinated controls challenged with a virulent clinical isolate 9 weeks later. A second vaccination after 6 weeks increased the LD50 by a further 16-fold. PMID- 8478108 TI - Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi. AB - The gene of the immunodominant major protein pC of Borrelia burgdorferi was previously cloned and sequenced (R. Fuchs, S. Jauris, F. Lottspeich, V. Preac Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503-509, 1992). pC is abundantly expressed on the outer surface of B. burgdorferi, as demonstrated by immunoelectron microscopy with monoclonal antibody L22 1F8. Accordingly, pC is renamed OspC, by analogy to the outer surface proteins OspA and OspB. Western immunoblot analysis of 45 B. burgdorferi isolates with monoclonal antibodies revealed that OspC is immunologically heterogeneous. Partial sequence analysis of the ospC gene confirmed the protein heterogeneity at the genetic level. We found that the degree of identity between the ospC partial sequences of five strains representing different OspA serotypes was only 63.3 to 85.4%. Immunological heterogeneity was also observed among representatives of the three newly designated genospecies of B. burgdorferi sensu lato, B. burgdorferi sensu stricto, B. garinii, and group VS461. Heterogeneity was confirmed for B. garinii at the genetic level. The ospC gene was also cloned from strains that did not express OspC, and antibody-reactive OspC was expressed in Escherichia coli. In addition, OspC-expressing variants were obtained from a nonexpressing strain by plating single colonies on solid medium. These findings confirm that the ospC gene is also present in nonexpressing strains. Because OspC is an immunodominant protein for the early immune response in Lyme borreliosis and was effective as a vaccine in an animal model, the immunological and molecular polymorphisms of ospC and OspC have important implications for the development of diagnostic reagents and vaccines. PMID- 8478109 TI - The cryptic ospC gene of Borrelia burgdorferi B31 is located on a circular plasmid. AB - Borrelia burgdorferi B31 cells lacking all linear plasmids or all but the 49-kb linear plasmid expressed the otherwise silent gene for the outer membrane protein OspC. In the first demonstration of a function for a circular plasmid of Borrelia spp., ospC was located on a 27-kb circular plasmid of B31. PMID- 8478110 TI - Cell-mediated immunity to Chlamydia pneumoniae measured as lymphocyte blast transformation in vitro. AB - The purpose of the present study was to analyze Chlamydia pneumoniae-induced, antigen-specific, cell-mediated immunity. Peripheral blood mononuclear cells of four persons infected with C. pneumoniae Kajaani 6 and 17 healthy volunteers were stimulated with antigen composed of whole elementary bodies of C. pneumoniae Kajaani 6 (CP-Ag). Definitive antigen-specific lymphoproliferation (LP) responses were developed after recent infection. The LP responses of healthy people to CP Ag varied considerably. There was no clear correlation between LP responses to CP Ag and those to an antigen prepared from Chlamydia trachomatis serotype L2 (r > or = 0.50, P < 0.1). A larger study is required to demonstrate whether the LP responses to CP-Ag can be used for the diagnosis of C. pneumoniae infection. PMID- 8478111 TI - Identification of eae sequences in enteropathogenic Escherichia coli strains from rabbits. AB - DNA sequences coding for attachment and for verotoxin production were investigated in a collection of enteropathogenic Escherichia coli strains from rabbits. All of the strains produced diarrhea after experimental infection, attached to the brush borders of the intestinal lining, and possessed homology to the eae probe, whereas strains isolated from healthy rabbits did not. Sequences homologous to the AF/R1 fimbriae of strain RDEC-1 were not found. One strain reacted with the probe for the Shiga-like toxin type I gene. PMID- 8478112 TI - Regulation of expression of major outer surface proteins in Borrelia burgdorferi. AB - We have characterized a Borrelia burgdorferi clone (CA-11 2A) that does not synthesize the major outer surface proteins, OspA and OspB. While the osp operon is intact and capable of expression, no mRNA transcript is detectable in this clone. These results suggest that osp operon expression in the B. burgdorferi clone can be regulated at the level of transcription. PMID- 8478113 TI - Biochemical and immunological properties of two forms of pertactin, the 69,000 molecular-weight outer membrane protein of Bordetella pertussis. AB - Two apparent isoforms of the virulence-associated 69,000-molecular-weight protein pertactin were purified from Bordetella pertussis. Mass spectrometry showed a difference of 2,060 Da, which may result from differential C-terminal cleavage of a larger precursor. Both forms were protective in a mouse model, eliciting bactericidal antibodies and reducing respiratory tract colonization. PMID- 8478114 TI - Lipopolysaccharide restores anti-Candida albicans growth inhibition activity of polymorphonuclear neutrophils from retrovirus-immunosuppressed mice. AB - It has been documented that the immune function of leukocytes may be markedly suppressed after infection of mice with the murine retrovirus Friend leukemia virus (FLV). Antimicrobial activity of polymorphonuclear neutrophils (PMNs) against Candida albicans is impaired after retrovirus infection of mice, and this occurs as early as 3 days after infection of genetically susceptible BALB/c mice. By 2 weeks after infection, there was essentially very little growth inhibition of C. albicans by PMNs from the FLV-infected mice. However, when bacterial lipopolysaccharide (LPS), a known activator of macrophages and PMNs, was added to PMNs from the FLV-infected mice, anti-C. albicans activity was restored to normal levels. This restoration of anti-C. albicans activity of FLV-infected mouse PMNs was observed after stimulation with as little as 0.01 micrograms of LPS per ml. The data obtained show that the impaired antimicrobial function of PMNs from retrovirus-infected mice can be readily restored by a biological response modifier such as bacterial LPS. PMID- 8478115 TI - Arcobacter (Campylobacter) butzleri-associated diarrheal illness in a nonhuman primate population. AB - After DNA hybridization identified an isolate from an ill rhesus macaque (Macaca mulatta) as Arcobacter (Campylobacter) butzleri, we initiated a study to determine whether A. butzleri was associated with diarrheal disease in nonhuman primates at the Yerkes Primate Research Center. By using Campy-CVA medium incubated at 35 degrees C, 15 A. butzleri isolates were obtained from 14 macaques; 7 macaques were coinfected with Campylobacter coli and Campylobacter jejuni. A. butzleri was not isolated from normal feces, despite the fact that feces from 76 macaques were cultured at necropsy. Histologic evaluation of colonic specimens from three macaques from which A. butzleri had been isolated showed mild to moderately severe chronic, active colitis. Ribotype analysis of the 15 A. butzleri isolates revealed nine different strains; these data suggest that A. butzleri may be endemic in this primate population and that a point source of infection is unlikely. This is the first report of the presence of A. butzleri in juvenile and adult macaques with diarrhea, and it may present an opportunity to study the pathogenesis of this organism, which appears to be associated with persistent diarrhea in humans. PMID- 8478116 TI - Isolation, expression, and nucleotide sequencing of the pilin structural gene of the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius. AB - In this study we isolated the pilin gene from the Brazilian purpuric fever (BPF) clone of Haemophilus influenzae biogroup aegyptius, expressed the gene in Escherichia coli, and determined its nucleotide sequence. Comparison of the nucleotide sequence of the BPF pilin gene with the sequences of pilin genes from strains of H. influenzae sensu stricto demonstrated a high degree of identity. Consistent with this observation, hemagglutination inhibition studies performed with a series of glycoconjugates indicated that BPF pili and H. influenzae type b pili possess the same erythrocyte receptor specificity. PMID- 8478117 TI - Reversal of age-associated decline in immune response to Pnu-imune vaccine by supplementation with the steroid hormone dehydroepiandrosterone. AB - Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine. PMID- 8478118 TI - Cutaneous leishmaniasis in mast cell-deficient W/Wv mice. AB - Genetically mast cell-deficient W/Wv mice infected with Leishmania amazonensis showed progressive development of ulcerative skin lesions. However, no significant differences between the W/Wv mice and the normal littermates with respect to size of the lesions, anti-Leishmania immunoglobulin E antibody, and the number of eosinophils accumulated in the lesions were observed. PMID- 8478119 TI - Characterization of an aromatic amino acid-dependent Listeria monocytogenes mutant: attenuation, persistence, and ability to induce protective immunity in mice. AB - A transposon insertion mutant of Listeria monocytogenes was shown to be deficient in prephenate dehydratase, an enzyme acting late in the pathway for biosynthesis of phenylalanine. This mutant had reduced virulence in mice. The mutant and parent strains persisted to the same extent in the tissues of infected mice and elicited similar degrees of splenomegaly. Mice vaccinated with the mutant were protected significantly from subsequent challenge with virulent L. monocytogenes. PMID- 8478120 TI - Identification and characterization of serotype 4-specific antigens of Ureaplasma urealyticum by use of monoclonal antibodies. AB - Monoclonal antibodies against Ureaplasma urealyticum serotype 4 were produced by immunizing BALB/c mice with whole-cell antigens of the U. urealyticum serotype 4 reference strain. Ten monoclonal antibodies differentiated into two groups were found: one group included five monoclonal antibodies recognizing a band in immunoblotting that had a molecular mass of 81 kDa, and a second group included another five monoclonal antibodies recognizing three bands in immunoblotting that had molecular masses of 81, 75, and 71 kDa. Fifteen clinical U. urealyticum isolates were selected for serotyping with serotype 4-specific monoclonal antibodies and polyclonal antisera 1 to 14. The results obtained with polyclonal and monoclonal antibodies suggest the existence of heterogeneity of the serotype antigens among clinical isolates of U. urealyticum serotype 4. PMID- 8478121 TI - Antigenic analysis of the major outer membrane protein of Haemophilus somnus with monoclonal antibodies. AB - The major outer membrane protein of Haemophilus somnus possesses at least five distinct epitopes. Three surface-exposed epitopes on the major outer membrane protein include a conserved epitope with potential for development of a vaccine and a diagnostic test and two variable epitopes responsible for antigenic differences among strains; the remaining two epitopes are well preserved among strains but not exposed on the cell surface. PMID- 8478122 TI - TH1 and TH2 T-cell subsets are differentially activated by macrophages and B cells in murine leishmaniasis. AB - The role of antigen-presenting cells in the differential expansion of TH1 and TH2 T cells in murine leishmaniasis was investigated. In general, macrophages preferentially induced gamma interferon and interleukin-2 secretion by syngeneic Leishmania-specific T cells, whereas B cells were more efficient in activating interleukin 4 production. B cells from susceptible BALB/c mice were better in inducing TH2 responses than B cells from resistant C57BL/6 mice, whereas macrophages from C57BL/6 mice were superior to BALB/c macrophages in inducing TH1 responses. PMID- 8478123 TI - Chemotaxis of leptospires to hemoglobin in relation to virulence. AB - A guinea pig-lethal line of Leptospira interrogans serovar copenhageni strain Shibaura, but not an avirulent line of the same strain, moved in larger numbers toward hemoglobin than toward distilled water (control) in a U-shaped polypropylene tube. L. interrogans serovar lai strains 017 and KH-1, which were also guinea pig lethal, showed a similar move to hemoglobin. No such move toward hemoglobin was shown by 14 avirulent strains of L. interrogans (with one exception) or any of the 8 strains of L. biflexa tested. PMID- 8478124 TI - Overtreatment with restorative dentistry: when to intervene? AB - Traditional restorative dental treatment has many shortcomings and has not been shown to be an effective method for managing caries. In spite of this, many dentists continue to be powered by an aggressive restorative approach which may result in unnecessary treatment and which must now be seen as inappropriate. There is a pressing need for a greater understanding as to the precise criteria that dictate the need for both non-invasive (reversible) preventive measures and invasive (irreversible) restorative treatment. This paper examines these criteria and provides decision trees with respect to the clinical management of carious lesions and teeth with existing restorations, showing when, and what type of, intervention is required. The assessment and management of fissured tooth surfaces receives special attention. It is demonstrated that while many clinical situations warrant clinical intervention, often this should be entirely preventive and of a non-invasive type. PMID- 8478125 TI - Improving oral health through understanding the meaning of health and disease in a Chinese culture. AB - Advances in modern technology have undoubtedly been of benefit to dentistry in its preventive and curative activities for populations worldwide. Studies, mainly from Western societies, show nonetheless that utilisation of services or adoption of preventive methods are not taken up at satisfactory levels. The focus of this paper is on the special problems in a Chinese society where major differences exist between the traditional lay health concepts and the modernised professional ones. Traditional Chinese health concepts comprise the balance between and interaction of 'Yin' and 'Yang', the vital forces in both the universe and in man's body, as the basis for maintaining health. To restore a disturbed equilibrium of vital forces, which will manifest itself as disease, a range of dietary products are available in Hong Kong, for example cooling herb tea to reduce fire from the stomach producing gum disease. Seeking dental treatment from dentists could be delayed or made 'unnecessary' due to reliance on home remedies. This could reduce the effectiveness of any planned health education activities and dental services available for improving the oral health status of the community according to prevailing Western concepts. An understanding of the cultural meaning of dental disease is fundamental to changing beliefs and attitudes of people in order to improve the oral health of the community. PMID- 8478126 TI - Management of elderly patients in the private practice system. AB - The distribution of the world's population has resulted in a significant increase in both the number and percentage of older adults in the industrially developed countries. The ageing populations in these countries are tending to maintain natural teeth longer and so require preventive and restorative dental services as they age. The majority of these populations live in the community and are functionally independent while a much smaller minority have become frail. An even smaller minority are institutionalised, hospitalised or home-bound. The majority of those who live in the community can utilise the services of dentists working in their own private offices or government clinics provided dentists are sensitive to their needs. PMID- 8478127 TI - Needs for tooth replacement. AB - The prime objective of dental care is maintaining a natural functional dentition for life. It is expected that a growing group of adults will keep their dentition into old age. Although routine prosthodontic care will still be important in the future the treatment strategy for older adults and elderly people with a reduced dentition does require a different approach. The traditional approach in prosthetic therapy was guided primarily by morphological criteria aimed at preservation of complete dental arches, which resulted in emphasis on quantity in dental care. Nowadays requirements such as aesthetics and functional comfort are considered more important and more easily achieved. In the presented principles for treatment planning the importance of a thorough preliminary treatment is stressed. Furthermore, needs for tooth replacement are discussed and guidelines are given for a preventive prosthodontic treatment approach in severely broken down dentitions and edentulous patients. PMID- 8478128 TI - The application of the theoretical model WHO/FDI planning system to an industrialised country: France. AB - The results of the application of the WHO/FDI planning system to a specific situation in an industrialised country provide valid arguments in favour of its use. It is shown to be an aid to planners when estimating oral health personnel requirements and emphasises the necessity of obtaining basic information on the oral health status and demand for treatment in industrialised countries. The strength of the system lies in the fact that it enables the user to forecast requirements, by age cohort and by type of care, while at the same time including socio-economic variables which have a major influence in industrialised countries with moderate caries levels. This flexibility of use enables the system to be adapted, if necessary, or even improved, according to the constraints which may result from a specific situation analysis. PMID- 8478129 TI - Stomatological treatment of patients with artificial heart valves: coagulation control and antibiotic cover. PMID- 8478130 TI - Age and culture: influences on oral health behaviour. AB - The role of patient age and cultural background in predicting dental service utilisation and self-care behaviours is discussed in the context of a person environment model of oral health. This model suggests that dental behaviours are a function of patient characteristics such as age, gender, culture, perceived dental needs and health beliefs, as well as characteristics of the dental delivery system such as cost, availability of third party payment systems and the accessibility of dentists who are viewed by patients as understanding and sympathetic to their needs. Each of these elements of person and environment is reviewed, with examples of research that has found associations between them and consequent dental behaviours. PMID- 8478131 TI - Caries prevention--a continuing need. AB - The frequently iterated, optimistic view of the demise of caries is not supported by the epidemiologic data. What is in evidence is a changing pattern of caries in developed countries. Among the young there is a polarisation in prevalence with 20 per cent of the children experiencing 70 per cent of the decay. The ageing population is at increasing risk because of longer tooth retention and exposure of root surfaces. A realistic view would envision control rather than extinction of caries with enhancement of current methods of combating tooth decay and more effective employment of multiple anticaries strategies. PMID- 8478132 TI - Role of Ca-P-F in caries prevention: chemical aspects. AB - The fluoride agents used in caries prevention can be divided into two broad categories: systemic and topical, although this division is not exempt from ambiguities. A review is given of the efficacy of systemic (fluoridated water and supplements) and topical agents. The latter include high concentration (12,000 ppm F) solutions, fluoridated dentifrices and mouthrinses. Emphasis is placed on the concept that there is no unique mode of action of the fluoride agents; their beneficial effects are related to different mechanisms depending on the agent and the mode of usage. Chemical models are advanced to explain the effect of the various agents. Of particular interest is the chemistry involved with dentifrices containing dicalcium phosphate dihydrate. It is shown that the presence of this compound greatly enhances fluoride utilisation in in vitro systems simulating the oral environment. PMID- 8478133 TI - In vivo studies with a dicalcium phosphate dihydrate/MFP system for caries prevention. AB - Recent basic studies have shown that increasing supersaturation with respect to dicalcium phosphate dihydrate (DCPD), above and beyond the amount present in saliva, enhanced the efficacy of fluoride in vitro. Since the combination of monofluorophosphate (MFP) with DCPD abrasive is unique for fluoride stability, dentifrices containing the combination were evaluated in a variety of in vivo tests. MFP with silicon dioxide (silica) abrasive at an equivalent fluoride concentration was used for comparison. The influence of slurries of DCPD or silicon dioxide on the intraoral plaque pH was measured following sucrose challenge in humans. The data indicated that DCPD slurries were more effective than silica in preventing plaque pH drop when compared to silica. A toothpaste containing MFP and DCPD was significantly more effective than an MFP/silica toothpaste. A toothpaste containing radiolabeled DCPD was applied topically in rats' teeth during a cariogenic challenge. The results showed that calcium45 was incorporated into the enamel with a concomitant reduction in enamel solubility. In a rat caries study using MFP/DCPD, matching placebo and MFP/silica, MFP/DCPD dentifrice showed a significantly greater reduction in smooth surface caries. Two dentifrices were also tested in an in situ human model for fluoride uptake in artificial root caries lesions where MFP/DCPD provided a significantly higher fluoride uptake than MFP/silica. A second in situ study in humans evaluated the same dentifrices. MFP/DCPD increased salivary plaque calcium and fluoride. These results of laboratory, animal and in situ studies taken together indicate that the MFP/DCPD combination is unique in providing extra supersaturation in saliva and plaque with concomitant enhanced anticaries efficacy. PMID- 8478134 TI - Clinical studies on MFP/calcium containing abrasive. AB - Monofluorophosphate (MFP) is unique in that its calcium salt is relatively soluble. Because of this property MFP can be combined with a dicalcium dihydrate (dical) abrasive in a dentifrice formulation without loss of efficacy. It has been reported that fluoride uptake by artificial lesions in enamel and dentine is significantly greater from an MFP formulation containing dical than from an equivalent calcium-free formulation. Additionally, it has been shown in an in situ remineralisation study that brushing with MFP dical significantly increases the levels of fluoride and calcium in plaque, and produces a concomitant increase in remineralisation of artificial caries lesions, as compared to brushing with MFP silica. All of the foregoing suggests that dical may enhance the benefit of MFP in a dentifrice formulation. MFP dentifrices have been tested more exhaustively in human clinical trials than any other form of fluoride dentifrice. In some trials the test formulation contained dical while in others a non-calcium abrasive system was employed. Collectively, studies of F/dical formulations have not produced more impressive results than studies of calcium-free MFP agents. However, there has never been a direct comparison of the conventional 0.76 per cent sodium monofluorophosphate dentifrice in a dicalcium phosphate abrasive system with a dentifrice containing a similar level of MFP combined with a non calcium containing abrasive. In the closest approximation to such a study, an MFP/NaF dentifrice with a dical abrasive was compared to an MFP/NaF dentifrice with a silica abrasive system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478135 TI - Age distribution of histologic types of breast carcinoma. AB - The large number of cases in the Surveillance, Epidemiology and End Results (SEER) program of the US National Cancer Institute allowed a detailed analysis of the age distribution of the histologic types of invasive breast carcinoma. Between ages 50 and 85 years in females, the age-specific incidence rate shows little change for medullary, inflammatory and apocrine carcinomas; is about doubled for Paget's disease and for ductal, lobular, tubular and metaplastic carcinomas; and increases to 4 to 8 times the menopausal level for mucinous, papillary and signet-ring-cell carcinomas. The peri-menopausal break on the age incidence curve is most marked for carcinomas of predominantly lobular origin and virtually absent for carcinomas of predominantly ductal origin. In males, the age distribution of papillary carcinoma is similar to that of all types combined, whereas that of mucinous carcinoma is skewed towards older ages, as in females. PMID- 8478136 TI - 12(S)-HETE promotes tumor-cell adhesion by increasing surface expression of alpha V beta 3 integrins on endothelial cells. AB - The present work was undertaken to investigate the regulatory role of 12(S)-HETE, a lipoxygenase metabolite of arachidonic acid, in the surface expression of alpha v beta 3 integrin receptors in endothelial cells (rat aortic endothelial cells, or RAEC). Several monoclonal and polyclonal antibodies localized alpha v beta 3 in focal adhesions in both subconfluent and post-confluent RAEC. RAEC alpha v beta 3 integrins were further characterized by immunoblotting and immunoprecipitation. 12(S)-HETE, but not 12(R)-HETE or other lipoxygenase-derived hydroxy fatty acids, induced a dose-dependent increase in alpha v beta 3 surface expression in RAEC, which was antagonized by prostacyclin or its analog iloprost as well as by 13-HODE, a 15-lipoxygenase product of linoleic acid. 12(S)-HETE promoted RAEC adhesion to vitronectin, an effect inhibited by antibodies against alpha v beta 3. 12(S)-HETE also promoted tumor-cell (W256 carcinosarcoma) adhesion to vitronectin, which was inhibited by various antibodies against alpha IIb beta 3 but not by an antibody against alpha v. W256 adhesion to 12(S)-HETE treated RAEC demonstrated a significant increase, which was inhibited by anti alpha v, -beta 3, or -alpha v beta 3 antibodies and by 13-HODE. Western blotting, immunoprecipitation and reverse transcription-polymerase chain reaction indicated that W256 carcinosarcoma cells expressed alpha IIb beta 3 integrins but not alpha v beta 3. The results suggest that the lipoxygenase metabolites [i.e., 12(S)-HETE and 13-HODE] play a significant role in modulating tumor-cell interactions with endothelium by enhancing endothelial cell integrin (e.g., alpha v beta 3) expression. PMID- 8478137 TI - Proliferation, migration and invasion of human glioma cells exposed to antifolate drugs. AB - The present study describes the effects of 2 folate antagonists, methotrexate (MTX) and the lipophilic antifolate trimetrexate (TMX) on 2 permanent human glioma cell lines (GaMg and D-54Mg) grown as monolayers and as multicellular tumor spheroids. In addition, the effects of drug exposure on tumor cell invasion was studied using a three-dimensional organ co-culture system. In monolayer cultures, TMX was a more potent inhibitor of cell growth than MTX, especially towards the GaMg cell line. The 2 drugs, however, showed similar cytotoxicity as assessed by the plating efficiency assay. Reduced ability of directional migration of cells on a plastic surface was seen by either antifolate usually at concentrations to 10-fold higher than those exerting a cytotoxic effect in the plating efficiency assay. TMX was somewhat more potent than MTX as an inhibitor of spheroid growth. When tumor spheroids were exposed to MTX or TMX at concentrations that caused 65 to 70% inhibition of cell migration, there was a latent period of 4 to 5 days before inhibition of spheroid growth ensued. Invasion was investigated in a co-culture system, where tumor spheroids were confronted with fetal rat brain cell aggregates. Neither drug reduced tumor cell invasion, although histological examination revealed toxic effects both in GaMg and in D-54Mg spheroids. We conclude that spheroids from human glioma cells were less sensitive to the antifolates than monolayers. For both drugs a latency period was observed before inhibition of spheroid growth. The spheroids retained their ability to invade normal brain tissue when exposed to levels of folate antagonists inhibiting spheroid growth. PMID- 8478138 TI - Estrone sulfate promotes human breast cancer cell replication and nuclear uptake of estradiol in MCF-7 cell cultures. AB - Estradiol levels in breast tumors from post-menopausal women are similar to those in pre-menopausal women even though plasma estrogens are much lower after the menopause. In situ estrogen production by the tumor provides a potential means of maintaining high estradiol levels in post-menopausal breast cancer tissue. The estrone sulfatase pathway has been proposed as the mediator of in situ estrogen production. A number of studies suggest that estrone sulfate may be converted into estradiol in breast tumors via the catalytic activity of estrone sulfatase and 17 beta-hydroxysteroid dehydrogenase. However, these studies used pharmacologic levels of estrogen sulfates and have not shown that physiologic levels can support biologic effects. Accordingly, the present study examined the dose relationship of estrone sulfate to a variety of biologic endpoints in MCF-7 breast cancer cells in culture. These cells converted physiologic concentrations of estrone sulfate to quantities of free estradiol capable of stimulating cell growth. Under these conditions, the nuclear steroids observed were free estrone and estradiol. Increase in cell number after 6 days of exposure to steroid required 100 nM estrone sulfate. However, S-phase, a more sensitive measure of cell proliferation, was stimulated by 0.1 nM estrone sulfate, a clearly physiologic concentration. Stimulation of estrogen-dependent protein markers such as pS2 and progesterone receptor required much higher concentrations of estrone sulfate. These effects were mediated through the estrogen receptor since the pure anti-estrogen, ICI 164384, blocked all effects produced by estrone sulfate. While it has been suggested that anti-estrogens may partly exert their effects by inhibition of sulfatase and 17 beta-hydroxysteroid dehydrogenase, this did not occur under our experimental conditions. These data provide evidence of the relevance of the estrone sulfatase pathway since biologic effects can be demonstrated in response to physiologic concentrations of estrone sulfate. PMID- 8478139 TI - TGF-beta induces an inhibitory effect of normal cells directed against transformed cells. AB - Co-cultivation of normal and transformed fibroblasts in the presence of exogenously added transforming growth factor type beta I (TGF-beta I) leads to a drastic reduction of colony-forming transformed cells. This inhibitory effect is dependent both on the dose of TGF-beta applied and the density of normal cells. It does not reflect a direct action of TGF-beta on transformed cells, but is rather induced by TGF-beta in normal cells. In the absence of exogenously added TGF-beta, normal cells exhibit a basal inhibitory activity, which can be abrogated by anti-TGF-beta. TGF-beta-mediated inhibition of transformed cells by normal cells may be considered as a novel potent controlling step in carcinogenesis. PMID- 8478140 TI - Abrogation of tumor-inhibitory MRC-OX8+ (CD8+) effector T-cell generation in rats by selective depletion of neutrophils in vivo using a monoclonal antibody. AB - These studies were designed to examine the role of neutrophils in transplantation immunity to syngeneic rat tumors. We have earlier reported that specific transplantation immunity to syngeneic transplanted tumors is abrogated by selective depletion of peripheral-blood neutrophils by administration of a monoclonal antibody (MAb) (RP-3) at the time of immunization with X-irradiated tumor cells. In order to elucidate the mechanisms of this phenomenon, we have now examined whether induction of the sensitized spleen cells that inhibit the growth of tumor cells is inhibited by RP-3 treatment at the time of in vivo priming with tumor-associated antigen (TAA). Neutrophils were required to induce the sensitized T cells responsible for tumor inhibition with Winn's assay. In addition, CD8+ T cells are proved to be effector cells in an assay system of tumor-growth inhibition using a diffusion chamber. Our results indicate that neutrophils are required for priming rats with TAA to induce CD8+ effector T cells in tumor inhibition. PMID- 8478141 TI - N-terminal peptide fragments of lipocortin-1 inhibit A549 cell growth and block EGF-induced stimulation of proliferation. AB - Lipocortin-1 mediates growth inhibition of glucocorticoids in A549 cells by suppressing the release of PGE2 necessary for their proliferation. We now show that 2 peptide fragments derived from the N-terminal portion of lipocortin-1 corresponding to amino-acids 13-25 and 21-33 also inhibited A549 cell growth and suppressed release of PGE2, whereas peptides 1-12 and 13-25 (Phe21; in which the tyrosine at position 21 was replaced by a phenylalanine residue) were inactive. Similarly, peptide 21-33 (Phe21) and a scrambled sequence of 13-25 failed to inhibit cell growth. Moreover, the EGF-induced stimulation of cell proliferation and PGE2 release in these cells was blocked by peptides 13-25 and 21-33, and also by peptides 1-12, 13-25 (Phe21) and 21-33 (Phe21), but not by a scrambled sequence of peptide 13-25. PMID- 8478142 TI - Spontaneous and induced differentiation of human melanoma cells. AB - Malignant melanoma cells can differentiate spontaneously in vivo and in vitro into cells with a finite lifespan. Analysis of differentiating cells from primary melanomas in culture revealed a flat, fibroblast-like morphology and expression of the fibroblast-associated marker leucine aminopeptidase (LAP). Differentiation was also observed in a minor sub-population of permanent cell lines derived from metastatic lesions. An experimental model of melanoma cell differentiation was then developed, using the pyrimidine analog bromodeoxyuridine (BUdR). BUdR treated cells had a flat morphology, were contact-inhibited, had up to 20-fold increased surface area, expressed LAP, no longer proliferated anchorage independently in soft agar, and 3 out of 4 cell lines were non-tumorigenic in athymic nude mice. Our results show that models of differentiation of melanoma cells can be established that help to define pathways of differentiation. PMID- 8478143 TI - Potentiation of DNA-adduct formation and cytotoxicity of platinum-containing drugs by low pH. AB - The low interstitial pH of tumor tissue is an important modulator of various anti tumor modalities. In order to explore the optimal conditions for the potentiating action of low pH on the cytotoxic activities of cis- and carboplatin, we have investigated the temporal aspects of drug activity and pH modulation in L1210 murine leukemia cells in comparison with various other drugs. Extra- and intra cellular pH of L1210 cells was modulated before, during and after drug exposure and survival of L1210 cells was determined. During short exposures, cytotoxicity of cisplatin and alkylating drugs was potentiated by conditions of low pH in the ranking order of: cisplatin, mitomycin C, melphalan and chlorambucil. Low pH had no effect on the cytotoxic activity of carboplatin and cytosine arabinoside and it inhibited the action of doxorubicin. During prolonged incubation at low pH, potentiation of cisplatin was increased and a more than 3-fold potentiation was induced in the case of carboplatin. Part of the latter effect was also manifested by 20 hr post-incubation in drug-free medium at low pH after a 4-hr exposure to carboplatin. Post-incubation did not increase the stimulating effect of low pH on the cytotoxic activity of melphalan and cisplatin. Acidification affected neither the uptake nor the extracellular hydrolysis of platinum-containing drugs. Under all circumstances, potentiation of platinum-containing drugs was accompanied by an increase in platinum-induced DNA modification, as detected by immunocytochemistry. PMID- 8478144 TI - Calcium intake and 28-year gastro-intestinal cancer mortality in Dutch civil servants. AB - The association between calcium intake and gastrointestinal cancer mortality was investigated in a 28-year follow-up study. Data were obtained from a general health examination in 1953-1954 among Dutch civil servants and their spouses, aged 40 to 65 years. Information from 2,591 participants was used for this study. Risk analyses were performed using logistic regression models with the highest quintile of calcium intake as reference. No statistically significant relation between calcium intake and gastrointestinal cancer mortality is observed, although the risk estimate for women with the lowest calcium intake is substantial. Odds ratios (OR) were adjusted for age, energy intake and dietary fiber. After inclusion of other potential confounders to the models (body-mass index and smoking habits), the results hardly differed. Both men and women who died of colorectal cancer had a lower mean calcium intake compared to the rest of the population. For women this was statistically significant. Our results suggest that a low calcium intake may be related to gastrointestinal cancer mortality among women of this study population. PMID- 8478145 TI - Cancer in Kampala, Uganda, in 1989-91: changes in incidence in the era of AIDS. AB - Re-establishment of the cancer registry in Kyadondo County, Uganda, has allowed estimation of incidence rates for the period September 1989 to December 1991. The results are compared with earlier data from the same area, and from other African cancer registries. The most striking feature is the emergence of Kaposi's sarcoma as the leading cancer in males (almost half of all registered cases) and the second most frequent (17.9%) in females. This parallels the evolution of the epidemic of AIDS. There were also marked increases in the incidence of both oesophageal and prostatic carcinoma, while the incidence of cancer of the penis and the urinary bladder declined, possibly as a result of improved standards of hygiene. In females, the incidence of cancer of the cervix has more than doubled since the 1950s, and is now among the highest recorded in the African continent. PMID- 8478146 TI - Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma. AB - Immunohistological methods were used to examine the relation between the metastatic potential of melanoma and expression of the neuroglandular antigen (CD63) and other members of this family of molecules, CD53, CD37, CD9 and the target of an anti-proliferative antibody (TAPA-I), as well as MHC-class-I and -II antigens. The criteria used to establish metastatic potential were their relation to thickness of the primary melanoma, and differences in expression between vertical and radial growth phases of primary melanoma and between primary and metastatic melanoma. Studies on basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were also included as controls for malignant skin cancers with low metastatic potential. Expression of CD9 and MHC-class-I antigen was found to be inversely related to thickness of the primary tumor, and CD9 was expressed predominantly on primary rather than on metastatic tumors. CD9 expression correlated with MHC-class-I expression on melanoma, and both were expressed on BCCs and SCCs having low metastatic potential, but not on compound nevi. CD63 and TAPA-I were expressed on nevi but not on SCC and BCC. Leu 13 is a molecule associated with TAPA-I in lymphomas, and was found to be expressed in sections from 5 out of 34 primary and 5 out of 21 metastatic melanoma. CD53 and CD37 were not detected on melanoma. Our results indicate that several members of the neuroglandular antigen are expressed in melanoma and that low expression of CD9 on primary melanomas might have prognostic significance with respect to the potential for metastasis. PMID- 8478147 TI - Expression of P-cadherin in gastric carcinomas and its reduction in tumor progression. AB - The expression of P-cadherin, one of the Ca(2+)-dependent cell-cell adhesion molecules, in human gastric carcinomas was examined by Northern blotting, Western blotting and immunohistochemistry. P-cadherin mRNA was expressed in all the gastric carcinoma tissues examined, whereas no message was detected in non neoplastic mucosa. By Western-blot analysis, P-cadherin protein was expressed in 83% and 29% of the well-differentiated and poorly differentiated gastric adenocarcinomas, respectively, the incidence being significantly different. Immunohistochemically, P-cadherin immunoreactivity was localized on the cell surface or the cell-to-cell borders of well-differentiated adenocarcinomas. P cadherin was not detected in Borrmann's type-4 or scirrhous carcinomas where the tumor cells proliferate diffusely with productive fibrosis. The level of P cadherin expression in stage-2 carcinomas was significantly higher than in stage I carcinomas. In the case of patients in stages 2 to 4, however, the level of P cadherin expression decreased as the stage progressed, the difference between stages 2 and 3 and between stages 3 and 4 being significant. Our findings suggest that P-cadherin might play an important role in the development of well differentiated gastric adenocarcinomas and the decreased expression of P-cadherin might be responsible for the infiltrative growth and progression of gastric carcinomas. PMID- 8478148 TI - Analysis of T-cell-receptor variable gene segment usage in peripheral-blood lymphocytes of advanced cancer patients. AB - Advanced cancer patients generally display impaired T-cell immune functions. The underlying mechanisms are not well understood. The aim of this study was to analyze whether major alterations of TCR variable gene segment usage could be detected in the blood of these patients. Seventeen individuals with various malignancies were tested using PCR and a panel of V-gene-segment-sub-family specific (V alpha 1-w29/V beta 1-w24) oligonucleotide primers. The results indicate that these cancer patient lymphocytes expressed most V alpha and V beta sub-family specificities, similarly to the lymphocytes of healthy donors (n = 10). This suggests that immunodepression in advanced cancer patients is not related to major deletions in their T-cell repertoires. We also compared the mean relative expression of each V-sub-family specificity of patients and healthy donors by quantitative densitometric analysis. We found significant differences in 4 V beta specificities (and no V alpha). Our analysis identified unique T-cell sub-sets putatively involved in the mechanisms leading to immunodepression in advanced cancer patients. Alternatively, the observed differences in terms of V beta specificity expression may reflect the host response against the tumor. PMID- 8478149 TI - Integrin expression in cutaneous malignant melanoma: association of the alpha 3/beta 1 heterodimer with tumor progression. AB - The cell-surface heterodimers of the integrin family of molecules, which mediate cell-cell and cell-substratum interactions, are likely to be functionally relevant in local and metastatic tumor growth. In the present study we have analyzed whether the alpha 3/beta 1 receptor for collagen, laminin and fibronectin undergoes changes in expression during tumor progression in cutaneous malignant melanoma (CMM). The results of this study have demonstrated that, while low levels of VLA3 expression are detectable in benign lesions, in primary melanomas the heterodimer undergoes progressive increase in expression which correlates with the degree of dermal invasiveness. Metastatic lesions were found VLA3 positive in 82% of cases. Furthermore, the heterodimer is homogeneously expressed in multiple autologous metastases. The presence of VLA3 correlates with detection of at least one of the ligands in 45% of the cases studied. These findings provide additional evidence that tumor progression in CMM is associated with changes in integrin phenotypes which include the alpha 3/beta 1 heterodimer. PMID- 8478150 TI - Breast cancer risk in mothers of multiple births. AB - Data from an international case-control study of breast cancer that was conducted in the 1960s were used to examine whether multiple births affect the risk of breast cancer in the mother. Among 2821 parous breast-cancer patients, 88 had had one or more multiple births, whereas among 8882 controls 247 had had one or more multiple births; the logistic-regression-adjusted odds ratio (OR) was 1.21, the 95% confidence interval (CI), 0.94 to 1.55. The OR was significantly elevated during the 15-year period following the latest multiple birth (1.76; CI, 1.12 to 2.75), but declined toward the null afterwards. A late first pregnancy imparted a substantially higher breast-cancer risk when it was multiple rather than singleton; the OR was 2.34 for a multiple and 1.48 for a singleton first pregnancy when the cutoff point was 30 years, and 4.58 and 1.57, respectively, when the cutoff point was 35 years. Since multiple pregnancies are characterized by higher levels of pregnancy estrogens, the results of this study would be compatible with the hypothesis that these hormones may be responsible for the transient increase in breast-cancer risk following a term pregnancy and, in particular, a multiple term pregnancy. The long-term reduction of breast-cancer risk is probably due to a different mechanism, most likely the terminal differentiation of susceptible mammary-gland cells. PMID- 8478151 TI - Studies on the role of platelet eicosanoid metabolism and integrin alpha IIb beta 3 in tumor-cell-induced platelet aggregation. AB - Platelet eicosanoid metabolism resulting from tumor-cell-induced platelet aggregation (TCIPA) was examined in a homologous in vitro system. Rat Walker 256 carcinosarcoma cells induced the aggregation of rat platelets via a thrombin dependent mechanism with concomitant production of eicosanoid metabolites (e.g., 12-HETE, TXA2). TCIPA was dependent on the concentration of tumor cells inducing aggregation, as well as cyclooxygenase and lipoxygenase products. Cyclooxygenase inhibitors, but not lipoxygenase inhibitors, blocked platelet aggregation induced in vitro by a low concentration of agonist. At a high agonist concentration, neither cyclooxygenase nor lipoxygenase inhibitors alone affected platelet aggregation; however, the combined inhibition of both the cyclooxygenase and lipoxygenase pathways resulted in subsequent inhibition of platelet aggregation regardless of agonist concentration. The extent of platelet TXA2 and 12-HETE biosynthesis was likewise dependent on and correlated with agonist concentration. The inhibitors used in this study did not significantly inhibit protein kinase C activity at the doses tested. Platelet surface glycoprotein alpha IIb beta 3 play an important role in platelet aggregation. The effect of platelet cyclooxygenase and lipoxygenase inhibition in regulating alpha IIb beta 3 surface expression was examined by flow cytometric analysis. Thrombin stimulation of washed rat platelets resulted in significantly increased surface expression of platelet alpha IIb beta 3 integrin complex. The enhanced surface expression was not inhibited by a cyclooxygenase inhibitor (aspirin), a thromboxane synthase inhibitor (CGS-14854) or a thromboxane receptor antagonist (SQ 29,548), nor was it stimulated by a thromboxane A2 mimic (pinane-thromboxane A2). However, alpha IIb beta 3 expression was blocked by lipoxygenase inhibition and stereospecifically increased by the platelet lipoxygenase metabolite 12(S)-HETE. These results suggest that both the platelet lipoxygenase and cyclooxygenase pathways are important for TCIPA but that different mechanisms of action are involved. PMID- 8478152 TI - We need a guerrilla war on drugs. PMID- 8478153 TI - The "rainbow" model: an attempt at a global approach to the drug problem. AB - A global, tridimensional, and comprehensive model for the drug problem is presented. On a flat matrix with five components (growing, production, processing, traffic/distribution, and consumption) and seven dimensions (individual, family, restricted group, neighborhood, city/region, national, and international), six different perspectives are employed (psychobiological, social/political, economics, legal, historical/cultural, and geographical). Each psychoactive substance may be analyzed separately. PMID- 8478154 TI - Personality and cigarette smoking in Italy, Poland, and the United States. AB - This study reports data on over 700 young adults, undergraduate and medical students attending the University of Vermont, the University of Rome, and the Warsaw Medical Academy. Each subject provided information about cigarette smoking history and completed several personality, Type A, and life events inventories. Subjects were classified as nonsmoker, ex-smoker, and smoker. Each measure was analyzed by ANOVA on this basis, with gender and country as additional main effects. Smokers were found to have higher state anxiety, a lower lie score, and were more Type A than ex-smokers and nonsmokers, but they tended to report fewer life events and of lower value. PMID- 8478155 TI - Substance misuse and comorbid psychopathology in a high-risk group: a study of siblings of cocaine misusers. AB - Vulnerability to drug misuse and psychopathology was explored among 673 siblings of 298 opioid-addicted probands. Disorders were evaluated based on family history information obtained from the proband. Results indicated that (1) siblings of cocaine misusers showed high vulnerability to developing drug misuse, alcoholism, and antisocial personality disorder; (2) siblings of probands with specific comorbid diagnoses were vulnerable to developing a range of disorders (no specificity of aggregation was found); (3) proband major depression was related to a broad spectrum of sibling disorders; (4) the presence of a major psychiatric disorder was strongly associated with substance misuse among siblings; (5) psychopathology appeared to precede drug misuse in terms of age of onset. These findings corroborate those previously obtained with siblings of opioid addicts, and they are discussed in terms of implications for the classification and treatment of substance misuse. PMID- 8478156 TI - Psychosocial correlates of drug use among Latino youth leading autonomous lives. AB - Drug use and psychosocial profile of young Central American immigrants in Washington, D.C., were compared to the National Household Survey of Latinos. The immigrants showed: (1) more exposure to alcohol and illicit drugs; (2) interrelated marijuana, cocaine, PCP, and hallucinogenic drug use; and (3) a positive association between psychosocial competency and ratio of perceived supports/threats. Drug involvement intensity was negatively associated with psychosocial competence and positively with instrumental drug use, CAGE scores, and problems. Crisis scores and drug involvement were related only in the high support/threat group. Supportive environments may be more effective than threats in preventing drug use. PMID- 8478157 TI - Alcohol use, depressive symptoms, and cultural characteristics in two Mexican American samples. AB - We modeled associations of quantity and frequency of alcohol use with depressive symptoms (negative affect, lack of positive affect, somatic disturbance, interpersonal problems) in two household surveys of Mexican-Americans (Ns = 1,313 and 3,577). Multivariate analyses controlled cultural (immigration, acculturation) and demographic (age, income, household size, marital status, employment status) characteristics, and assessed interactions of these two classes of predictors. Alcohol use was inconsistently related to depression. In some analyses, cultural characteristics accounted for associations of alcohol use with depression. In others, associations of alcohol use with depression depended on cultural characteristics. Associations of drinking with depression tended not to be robust across samples. PMID- 8478158 TI - Personality characteristics of adult children of alcoholics, other adults from dysfunctional families, and adults from nondysfunctional families. AB - This study used the California Psychological Inventory (CPI) to examine the personality characteristics of adult children of alcoholics. The sample was noncollege age adults (N = 174). Subjects responding to advertisements were grouped into Adult Children of Alcoholics (ACOA) (56%), Adults with Dysfunctional Family Histories (ADFH) (21%), or Adults without Identified Dysfunctional Family Histories (AIDFH) (23%). Results indicated that the ACOA group was different from the AIDFH group on nine of the 28 CPI scales, but there were no significant differences between the ACOA and ADFH groups. The validity of clinical impressions of ACOAs and the utility of considering ACOAs as a distinct field of study are discussed. PMID- 8478159 TI - Depression and anxiety among Afro-Caribbean general practice attenders in Britain. AB - Schizophrenia is diagnosed more frequently among Afro-Caribbeans in Britain than among white British controls. Studies among the general population indicate that non-psychotic disorders such as anxiety, depression and functional somatic symptoms are the commonest expression of psychiatric morbidity. Yet, among Afro Caribbean primary care attenders, rates of anxiety and depression appear lower than in the general population. This finding is at odds with the reportedly higher rates of schizophrenia among this group. The majority of authors favour socio-cultural explanations to account for the higher rates of schizophrenia. Yet many of the factors that are evoked to account for the greater incidence of schizophrenia would be expected to lead to higher rates of non-psychotic disorders in primary care settings. Possible explanations for these apparently contradictory findings are discussed. PMID- 8478160 TI - Comparison of adaptation to the home culture of Japanese children and adolescents returned from overseas sojourn. AB - A questionnaire based on the MMPI was administered to Japanese children aged between 6 and 18 years who had returned from an overseas sojourn of more than one year's duration (N = 1941) and a matched control group who had no overseas experiences (N = 1354). Overall females had more difficulty with friends, and scored higher on both psychological and physical symptoms. The older children had more complaints about life in Japan, difficulty with friends and physical and psychological problems. The differences between the returnee and control group were less in the age range between 7 and 9, but the overseas experience seemed to have positive effects between the ages of 10 to 15. The longer the children stayed overseas, the more they had complaints about life in Japan and difficulty with friends, and less negative attitudes towards overseas life. Children who had multiple overseas experiences had more problems such as anxiety, depression and mental complaints. Children's developmental stages and the amount of exposure to the foreign culture are therefore important determinants of their readjustment. The expectations of parents and the home culture to the returnee children, gender, and emphasis on academic achievement, must also be taken into account. PMID- 8478161 TI - Gender, generational and social support correlates of mental health in Asian immigrants. AB - A sample of 100 Asian immigrants, mainly from India and Pakistan, were interviewed in their native language (Urdu, Punjabi, Hindi or English) concerning their psychological adjustment to life in Britain. It was predicted that female Indo-Pakistan immigrants would have higher levels of psychological symptomatology than male immigrants; and that second generation immigrants would have higher levels of psychological symptomatology than the first generation immigrants did not have higher levels of psychological symptoms than the first generation immigrants. Social support networks of the subjects were not correlated with mental health. However for the two generations, there was evidence linking social support to mental health. The extent of acculturisation, as measured by identificational assimilation, was not correlated with mental health. Results are discussed in terms of the burgeoning literature in this field. PMID- 8478162 TI - Coping with adversity: testing the origins of resiliency in mental health. AB - This paper examines the multi-dimensional nature of resiliency to risk in mental health, and tests regression models of differential resiliency, based on two hospital-based clinical research projects. The first project involves adult children of problem drinkers, individuals who are at greater risk to alcohol abuse given their parents' pathology. The second involves schizophrenics diagnosed with varying dispositions to depression. The analyses reveal that for both adult children of problem drinkers and for schizophrenics, individuals have varying degrees of susceptibility to adversity and that these variations are based, to a large degree, on psychosocial concerns. Furthermore, the results show quite clearly that men and women suffer to varying degrees when exposed to the same kinds of adversity, and that the causal origins of resiliency are different for men and women. PMID- 8478163 TI - Exploring the feasibility of assessing perceived parental rearing styles in Spanish children with the EMBU. AB - Most of the available data on the dimensional structure underlying the EMBU--an originally Swedish measure designed to assess one's recollections concerning one's parents' rearing behaviour--has been obtained with adults or adolescents. In the present study, using exploratory factor analysis, an attempt was made to determine the EMBU factorial structure in a Spanish sample of children aged 7-12 years (N = 205). Four factors explaining only 24% and 25% of the total variance in the ratings of the fathers and those of the mothers, respectively, and being invariant across parental sex, were interpreted: Emotional Warmth, Rejection, Control Attempts, and Favouring Subject. Results with respect to the internal consistency reliability of the corresponding scales were satisfactory, as were homogeneity figures pertaining to each set of theoretically-related items. Higher order analyses of the first-order dimensions (mothers and fathers jointly) revealed three factors explaining 85% of the total variance. Control Attempts, Care (Rejection vs. Emotional Warmth), and Favouring Subject. The factorially derived (first-order) scales were uncorrelated with sex of the recipient. All scales (except Rejection) correlated sizeably, negatively, with age (medium effect size) pointing, as outlined, to the need to take into account the relevant normative, design and research implications in further investigation. Some similarities and differences with findings yielded previously with adults and adolescents are briefly pinpointed. PMID- 8478164 TI - A comparison of Type A behaviour pattern, hostility and Typus Melancholicus in Japanese and American students: effects of defensiveness. AB - A comparison of Type A behaviour pattern, hostility and Typus Melancholicus (TM) was examined in a sample of 228 Japanese and 121 American college students. It was found that: the Japanese students expressed Type A, especially hostility, less strongly than American ones; TM was seen to the same degree in both Japanese and American students; Type A was related to hostility and TM in both groups of students; and compared with American students, the Japanese students displayed the defensiveness more frequently, and there appeared to be a strong relationship between defensiveness and hostility. These results suggest the possibility that hostility, a component element of Type A, is manifested under the influence of defensiveness, which is partially related to a variety of different sociocultural contexts. PMID- 8478165 TI - Suicidal behaviour in people infected with human immunodeficiency virus: a literature review. AB - Suicidal acts seem to be more frequent in AIDS patients than in the general population: nevertheless, the interpretation of these findings remains uncertain, because an increased risk of suicide has been found in some groups at risk of HIV infection (homosexuals, i.v. drug users) irrespective of the presence of HIV infection. The lack of adequate registration of causes of death in mortality statistics, the difficulty of identifying AIDS cases, and the lack of appropriate reference populations in the majority of register-based studies and post-mortem investigations are the main methodological problems in this research area. PMID- 8478166 TI - Freud's influence on American political science. AB - In an effort to assess which of Sigmund Freud's theories have had an influence on political scientists in the United States, the author conducted a survey of the American Political Science Association. The results of the survey showed that two concepts, the concepts of repression and the unconscious, were deemed most useful for political analysis and/or teaching. This paper traces the origins and infusion of these two constructs into American political thought. PMID- 8478167 TI - A perceptually based method for enhancing pulmonary nodule recognition. AB - RATIONALE AND OBJECTIVES: Feedback of chest areas receiving prolonged gaze durations significantly increases nodule detection performance. Why feedback circling enhances performance when other cueing methods produce equivocal results was assessed. METHODS: Chest and noise images with nodule targets were used to determine: what type of cue is most effective; whether circling influences the way the eye samples the target; whether circling limits processing of distracting information outside its boundary. RESULTS: Circling improves performance more than cues with less complete boundaries and increases the accuracy and frequency with which nodules are fixated. Outside distractors were detected less often with than without the circle present. CONCLUSIONS: Circling isolates the abnormal region from the rest of the image, making disembedding and integration of nodule features more likely and insulates this region from distractors. The facilitative effects of circling are generalizable to other images in which low contrast targets are embedded in noisy backgrounds. PMID- 8478168 TI - Sonographic image degradation after barium enema. AB - RATIONALE AND OBJECTIVES: The authors previously showed that barium does not interfere with abdominal sonography performed after a biphasic upper gastrointestinal tract examination. This study was designed to assess the impact of a barium enema (BE) examination on the quality of abdominal sonography performed immediately after the barium enema. METHODS: Forty patients scheduled for routine barium enemas (22 air contrast and 18 solid column) were prospectively examined with abdominal sonography before and after their BEs. The resulting 80 sonograms were randomized; three radiologists blindly assessed the quality of images of each of six anatomic areas (aorta, pancreas, porta hepatis, gallbladder, and the right and left lobes of the liver). RESULTS: There was no statistically significant degradation of the images for the right and left lobes of the liver and the pancreas. However, the images for the gallbladder, porta hepatis, and aorta had a statistically significant (P < .05) degradation of their ultrasound quality following barium enema. CONCLUSIONS: Unlike upper gastrointestinal tract examination, BE examination does interfere with the quality of a subsequent abdominal ultrasonography. Thus, when both studies are required, sonography should be performed first. PMID- 8478169 TI - Fatty infiltration of the liver. Quantification by 1H localized magnetic resonance spectroscopy and comparison with computed tomography. AB - RATIONALE AND OBJECTIVES: The authors evaluated the degree of fatty infiltration of the liver in subjects with diffuse liver steatosis using image-guided 1H localized MR spectroscopy and correlated the magnetic resonance (MR)-determined fat fraction with the computed tomography (CT) liver/spleen density ratio and histologic evaluation. METHODS: MR measurements were performed at 1.5 T by applying a double-spin-echo localization sequence. Twenty-six patients underwent MR and CT examinations and ultrasound (US)-guided biopsy. Additionally, three healthy volunteers underwent MR examination. Steatosis severity was estimated using 1) the ratio between fat and total MR signal areas; 2) the ratio between liver and spleen CT number; and 3) histologic score. RESULTS: The linear correlation between MR fat/fat-plus-water signal ratio and CT liver/spleen density values ratio is statistically significant. Both techniques correlate well with histologic score. No significant correlation exists between water or fat T2 values and the severity of steatosis. CONCLUSIONS: 1H MR spectroscopy allows a noninvasive estimate of the hepatic fat content. PMID- 8478170 TI - Patient choice and nonionic contrast media. AB - RATIONALE AND OBJECTIVES: Because of the greatly increased cost of nonionic, low osmolar contrast material, some practitioners reserve its use for patients at high risk for an adverse contrast reaction. The authors attempt to evaluate the proportion of low-risk outpatients--when offered a choice between the more expensive but lower-risk nonionic and the cheaper but higher-risk conventional ionic contrast material--that would choose the nonionic media. METHODS: Two hundred and fifty consecutive outpatients awaiting contrast-enhanced computed tomography were included in this study. Patients at increased risk for a contrast reaction were excluded. The remaining 162 patients were informed of the risks and told of the availability of nonionic contrast media with its up to six-fold decrease in serious complications. They were also informed that if they chose the lower-risk nonionic agent, they would likely have to pay the additional $100 to $150 in cost. RESULTS: Of the 162 low-risk patients surveyed, 48% selected nonionic contrast media, and 63% believed that all patients should be informed of the risks of contrast material and of the availability of nonionic contrast. CONCLUSIONS: The data support providing patients at low risk for an adverse reaction informed consent about the relative risks of ionic and nonionic contrast material. PMID- 8478171 TI - Effects of ioversol versus iothalamate on endothelin release and radiocontrast nephropathy. AB - RATIONALE AND OBJECTIVES: Certain radiocontrast agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated. METHODS: Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop radiocontrast nephropathy. RESULTS: In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided. CONCLUSIONS: These results strengthen the hypothesis that endothelin release induced by radiocontrast agents is correlated with their renal toxicity and therefore, may play a role in radiocontrast nephropathy. PMID- 8478172 TI - Renal tubular effects of diuretics and X-ray contrast media. A comparative study of equimolar doses in healthy volunteers. AB - RATIONALE AND OBJECTIVES: The isotonic nonionic contrast medium iodixanol has been shown to increase urinary enzyme excretion less than the hypertonic contrast medium iopentol. The authors investigated whether this could be caused by different molar loads using enzyme excretion after diuretic administration as a model. METHODS: Matching molar doses of mannitol were given to two groups of 10 healthy volunteers. Furosemide was administered perorally to a third group of 10 persons. Urinary enzyme excretion was sequentially measured, and the results were compared to our previous findings after contrast-media administration. RESULTS: Equimolar doses of mannitol and contrast media (CM) induced similar changes in urine volume and free water clearance. Mannitol and furosemide increased the urinary excretion of N-acetyl-beta-glucosaminidase (NAG) and alkaline phosphatase (ALP) in the period 0 to 4 hours after administration, i.e. during peak diuresis, whereas both CM increased ALP significantly more, their effects still evident at 24 to 48 hours. Iodixanol had no effect on urinary NAG excretion, but iopentol increased NAG more than did mannitol. CONCLUSIONS: The early effect of CM on urinary enzyme excretion can be related, in part, to the increased diuresis, but the late effect apparent at 24 to 48 hours cannot be explained by the osmotic load of the CM. PMID- 8478173 TI - Comparison of different perfluorocarbons as ultrasound contrast agents. AB - RATIONALE AND OBJECTIVES: The sonographic properties of Fluosol 20% (F20), which was recently approved for clinical use as an oxygen carrier for coronary angioplasty, were compared to those of perflubron emulsion, which is still in clinical testing. METHODS: Contrast agents were evaluated in 21 normal rabbits divided into three groups of seven rabbits each. All rabbits received 2.7 g/kg of perfluorocarbon (PFC). One group received 2.7 ml/kg of an experimental formulation of perflubron emulsion AF0102, which contains 1 g of PFC in 1 ml of emulsion (P100), the other received 13.5 ml/kg of F20 (1 ml has 0.2 g of PFC), and the third received 13.5 ml/kg of P100 diluted to a 20% concentration (P20). All rabbits were scanned by a blinded sonographer before, during, and immediately after infusion, and then again at 30 minutes and 48 hours. Doppler enhancement, echogenicity of inferior vena cava lumen, echogenic enhancement of perfused tissues, and reticuloendothelial organs were assessed. RESULTS: P100 and P20 had nearly identical sonographic properties at all points. During their vascular phase they enhanced Doppler signal, filled the lumen of the IVC and hepatic veins with flowing echogenic reflectors, and enhanced perfused tissues. F20 had no detectable sonographic effect during its vascular phase. All three emulsions enhanced the liver relative to kidney to a similar degree at 48 hours. CONCLUSIONS: Because RE enhancement was similar for F20, P100, and P20, and because P100 and P20 had similar properties during the vascular phase, the lack of vascular effect of F20 could not be due to the different PFCs used in these agents, or due to the difference in the dilution or volume. The most likely cause for the observed sonographic behavior of F20 and P100 is the difference in emulsion formulation. PMID- 8478174 TI - Methods for mitigating soft-tissue injury after subcutaneous injection of water soluble contrast media. AB - RATIONALE AND OBJECTIVES: Water soluble contrast media may cause tissue injury by extravasation during intravenous injection during various radiologic examinations. The authors attempted to find out what kind of management could mitigate tissue injury when extravasation of water soluble contrast media occurs. METHODS: Sodium and meglumine ioxithalamate was injected subcutaneously into 240 hind feet of 120 rats that were divided into six groups according to the methods of experimental management. Experimental managements included the following: no further management (control), injection of distilled water, injection of normal saline, injection of hydrocortisone, hot water application, and cold water application. Gross morphologic changes in each group were compared with those in the control group. RESULTS: Only the saline injection group showed statistically significant decrease of tissue injury compared with the control group. CONCLUSIONS: Saline injection lessens the degree of soft-tissue injury at contrast media extravasation sites in rats. PMID- 8478175 TI - Magnetic resonance imaging after arterial portography with manganese dipyridoxal diphosphate. AB - RATIONALE AND OBJECTIVES: The authors assess performing hepatic magnetic resonance imaging (MRI) after arterial portography with manganese dipyridoxal diphosphate (MnD-PDP), a hepatobiliary contrast agent, as an invasive but potentially highly sensitive means of focal lesion detection. METHODS: Eight pigs underwent superior mesenteric artery catheterization and injection of 10 mumol/kg MnDPDP. Magnetic resonance imaging at 1.5 T (SE-140/10) was performed before, then at 15 and 30 minutes after injection. Seven or more days later, the same MRI protocol was performed after intravenous injection of 10 mumol/kg MnDPDP. RESULTS: Fifteen minutes after intra-arterial injection, enhancement of the liver predominated (86 +/- 13%), followed by the renal cortex (44 +/- 14%), pancreas (26 +/- 9%), and spleen (14 +/- 9%). At 30 minutes, enhancement of renal cortex significantly increased (50 +/- 14%). There was no significant difference in enhancement of the liver, spleen, pancreas, or renal cortex when we compared intra-arterial and intravenous administration. CONCLUSION: After the injection of 10 mumol/kg MnDPDP into the superior mesenteric artery of pigs there is no significant difference in visceral organ enhancement compared to intravenous administration. The data suggests that the hepatocyte binding sites may be overwhelmed by this dose and/or injection rate of MnDPDP. PMID- 8478176 TI - Mission, role, and responsibilities of an academic department of radiology. PMID- 8478177 TI - New radiopharmaceuticals for detecting infection. PMID- 8478178 TI - Intracranial aneurysms. PMID- 8478180 TI - Preparing a grant proposal. PMID- 8478179 TI - Use of radiologic studies by nonradiologists in academic publications: should radiologists care? PMID- 8478181 TI - Preparing a research grant application budget. PMID- 8478182 TI - Design of clinical radiologic research. AB - The components of clinical research design--the research question, the review of prior research, the study design, the study subjects, the study measurements, the statistical analysis, and the critical analysis--have been discussed. These components relate to the overall philosophy of the research process in the following manner. The driving force behind research is the desire to understand a universal truth (Fig. 6). The research question is formed to reflect the truth sought. Next defined is the specific target population and the phenomena of interest with regard to the sought-after truth. The study is then designed with a study plan detailing timing and location and an intended sample population chosen to reflect the target population. The phenomena of interest are translated into measurable intended variables. Care is needed to identify the systematic error that can be introduced at this stage; outside opinion can be invaluable. The actual study results from the implementation of the study design. The actual subjects may differ from the intended sample population due to a low recruitment rate or a large dropout rate. The actual measurements may differ from the intended variables due to unsuspected confounding variables or random errors. Statistical analysis is performed on the study findings to infer truth within the study. This truth may be affected by random and systematic errors in implementing the study. Truth in the study is then inferred to reflect truth in the universe. Systematic and random errors in study design may affect the validity of that deduction, but that deduction is the only way we have of understanding universal truth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478183 TI - Grantsmanship. PMID- 8478184 TI - Animal research. PMID- 8478185 TI - Tracking a grant through the NIH. Or, the radiologist who came in from the cold. PMID- 8478186 TI - NIH peer review of grant applications. Definitions, procedures, and suggestions. PMID- 8478187 TI - Investigative partnership with industry. PMID- 8478188 TI - Research in radiology departments. PMID- 8478189 TI - Radiology research. Not an amateur sport, but fun. PMID- 8478190 TI - Activities of the Conjoint Committee. Enhancement of diagnostic radiologic research and education. AB - Even though we have made much progress over the last decade, much still needs to be done. I am personally very pleased with the excellent management and authority of my coauthor, Joe Frank, in assuming the Acting Directorship of our DRRP. You will be hearing more from him in the immediate future about this research program, and he will be accessible to all of you, both individually and at our national meetings. We must continue to recruit representatives to fill responsible positions at the NIH, including Director for the DRRP at the National Cancer Institute. Further funding for equipment and personnel within the Diagnostic Radiology Research Laboratory also will be necessary. We are anticipating that the annual laboratory budget will increase further, but to provide additional resources, the Conjoint Committee plans to take an active role in encouraging foundations, corporations, and member societies to assist further with this effort. Most of the other disciplines within medicine--in fact, many individuals in your own medical school within other departments--have spent time at the NIH. It is this high-quality experience, in an environment that can provide both the research background and the cultivated personal relationships and interactions, that will foster a long-term research career. Clearly, the complementary role of both the intramural and extramural programs will allow diagnostic radiology to achieve excellence and true respect in the total research community of the Academy. Many people have been responsible for our success, and I have already mentioned a few.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478191 TI - The grantsmanship workshop 1986-1992 and radiology research funding. PMID- 8478192 TI - Assessment of anxiety, depression, and suspiciousness in the home care setting. AB - Home care nurses who are not trained as psychiatric nurses can meet the challenge of caring for clients with anxiety, depression, or suspiciousness. The home care setting provides more opportunity for prolonged periodic nurse-client interaction in the client's usual surroundings. Home care nurses have a further advantage over acute care nurses in that they tend to have a more developed concept of cultural and environmental influence. Assessing psychosocial issues requires nontangible tools, the most crucial of which is the ability to listen--to listen with ears and heart. Although test instruments may be useful, most assessment involves interview and observation. Drawing on these special opportunities and skills, the home care nurse can objectively collect and evaluate data to determine the presence of anxiety, depression, or suspiciousness in preparation for appropriately intervening. PMID- 8478193 TI - Psychiatric home care. A framework for assessment and intervention. AB - In this article, we will discuss how the theories of crisis intervention, self care, and behavior direct our psychiatric home care practice. A brief discussion of the theories will be followed by a case example that illustrates their application to a psychiatric home care situation. PMID- 8478194 TI - Family health assessment. AB - A family health assessment tool that focused on the family as the unit of care was developed. The tool adapted Gordon's 11 functional health pattern typology and categorized data using interview, observation, and measurement methods. PMID- 8478195 TI - Strategies for organizational change in home healthcare. AB - There has been an unprecedented increase in the use of home healthcare services in the past decade. Opportunities for the professional advancement of nurses and a decrease of healthcare costs abound with the growth of home healthcare, if home health services are managed wisely. A proactive approach to organizational change embracing four paradigms of organizational functioning will enable the nurse administrator involved in home healthcare to adequately confront the demands of the future. PMID- 8478196 TI - Learning styles and instructional processes for home healthcare providers. AB - The extension of ancillary nursing roles challenges registered nurses to devise pertinent and effective teaching and learning strategies in home healthcare educational orientation and inservice programs. A powerful method to strengthen preferred ways of learning and broaden learning styles to meet changing circumstances is described. PMID- 8478197 TI - Discharge planning. PMID- 8478198 TI - The mind-body connection. PMID- 8478199 TI - Home care nursing and psychosocial-emotional needs. How nursing diagnosis helps to direct and inform practice. PMID- 8478200 TI - Psychiatric evaluation and therapy. PMID- 8478201 TI - Polypharmacy: dangers of multiple-drug therapy in patients with immunodeficiency virus infection. PMID- 8478202 TI - Hospice home health aides. PMID- 8478203 TI - Chronic sorrow in multiple sclerosis. A case study. AB - Multiple sclerosis, one of the most common chronic disabilities among young adults, may potentiate the occurrence of chronic sorrow. Chronic sorrow differs from acute grief because it is permanent, periodic, and progressive in nature; it may be a normal component of chronic illness and disability. This study describes one woman's experience with multiple sclerosis, her chronic sorrow about the trajectory of her disability, her progressive loss of bodily function, and the stigma of chronic illness. It also reports some of the feelings experienced by her husband, the primary caregiver. PMID- 8478204 TI - International Hemoglobin Information Center (IHIC) variants list. PMID- 8478205 TI - Sex-linkage of the chicken ornithine transcarbamylase gene. AB - The chicken ornithine transcarbamylase gene has been mapped to the short arm of the Z chromosome, near the centromere. Radioactive in situ hybridization was performed using a human cDNA clone, and chromosomes were scored for silver grain accumulation. This represents the first documented case of a mammalian X-linked gene also being sex-linked in an avian species. The significance of this finding in the context of sex chromosome evolution is briefly discussed. Further, differential sex-related OTC expression, whereby females (ZW) consistently produce higher levels of the enzyme than males (ZZ), must imply a peculiar mode of OTC transcription regulation. PMID- 8478206 TI - Variable expression of tapetoretinal degeneration in northern Sweden. AB - In the county of Vasterbotten in northern Sweden, 20 families with 50 diagnosed cases and 53 sporadic cases of tapetoretinal degenerations (TRD), including retinitis pigmentosa (RP), were ascertained. The familial and sporadic cases were traced genealogically as far back as was possible. Ancestors born before 1890 (n = 12,033) were registered on a PC. The analysis of data showed that 7 families (20 cases) and 21 sporadic cases could be traced to ancestors in a parish in the northern part of the county. The results suggest, in that parish, a gene source of an autosomal recessive gene causing TRD, with varying phenotypic expression, including variants of RP. PMID- 8478207 TI - Ageing before mating and quinacrine ameliorate the expression of abnormal oocyte (abo) in homozygous Drosophila melanogaster females. AB - Several studies have shown that the characteristically skewed sex ratio among the progeny of abo homozygous females, derived from heterozygous stocks and mated to attached XY males, can be modified during homozygous stock-keeping. This amelioration seems to have a complex mechanistic background, and both loss of the blood transposon from chromosome 2, where abo is located, and amplification of a specific heterochromatic element (ABO) have been suggested to work in this direction. There is also an increased frequency of non-disjunction associated with abo, beside the poor recovery of X0 males. Experiments were performed to see if there was a coordinated loss of both phenotypic expressions during homozygous stock-keeping and if non-disjunction was amenable to modification by quinacrine. We found an unexpected spontaneous amelioration of the phenotypic expressions of abo despite heterozygous stock-keeping. The spontaneous amelioration of non disjunction and male lethality under heterozygous condition was coordinated while the process initiated by homozygosity slowly decreased non-disjunction and rapidly increased male recovery over generations, which may point to a mechanistic difference between the amelioration processes. Quinacrine was found to ameliorate the skewed sex ratio but did not affect non-disjunction. In these experiments larval and adult treatment, respectively, were employed and the respective controls revealed that also ageing before mating significantly increased male recovery and reduced non-disjunction. Ageing before mating and quinacrine seemed to act additively on male recovery, suggesting independent action, while interaction could be suspected between quinacrine and some ameliorating factor associated with brood. Some of the results also suggest that quinacrine acts indirectly and does not substitute for the abo gene product. Due to the action of quinacrine in other biological systems it is speculated that the compound compensates for a biochemical aberration in abo/abo females or their progeny, showing some relation to phospholipase activity and/or actin polymerisation state. PMID- 8478208 TI - Sister chromatid exchange in the goat (Capra hircus). AB - Lymphocyte cells from 30 Maltese and Syrian derivative goats (13 males and 17 females) reared in southern Italy underwent sister chromatid exchange (SCE) test. For the 902 cells we studied, the SCE-mean values were 6.6 +/- 3.0 per cell for both breeds. The SCE-frequency did not follow a Poisson distribution. The simultaneous visualization of SCEs and G-bands in the lightly stained chromatid allowed the study of SCE-distribution in chromosomes 1 and X. The number of SCEs in chromosome 1 was significantly higher (P > 0.001) than expected from relative chromosome length. No statistical differences between the numbers of SCEs in the active (early-replicating) and inactive (late-replicating) X-chromosomes of female cells were found. PMID- 8478209 TI - Cytogenetic patterns in 384 northern-Spanish patients with haematological disorders. AB - During 1988-1991, we have conducted cytogenetic analysis in 384 consecutive patients with suspected neoplastic haematological diseases. A total of 404 samples were evaluated with banding techniques; 66 patients had myeloproliferative syndromes (MPS); 64, chronic myeloid leukaemia (CML); 50, acute nonlymphocytic leukaemia (ANLL); 40, myelodysplastic syndromes (MDS); 39, lymphoproliferative disorders (LPD); 37, acute lymphocytic leukaemia (ALL); 31 with non-Hodgkin lymphomas; and 57 patients had benign disorders. The frequencies and the type of detected chromosomal abnormalities were, in most diagnostic groups, within the limits of previous reports. For lymphomas, LPD, and MPS these frequencies were lower than expected. 144 cases (44.8%) of the 295 de novo diagnosed cases showed structural rearrangements. Breakpoints involved in structural rearrangements cluster to 35 bands of the standard 650-banded karyotype. We have observed eight cases with new chromosomal rearrangements. PMID- 8478210 TI - Zygotene-pachytene substaging and synaptonemal complex karyotyping of boar spermatocytes. AB - Synaptonemal complex analysis, by electron microscopy of spread spermatocytes after phosphotungstic acid staining, made possible description of the chromosomal synaptic patterns and the synaptonemal complex karyotype of the pig (Sus scrofa domestica). The autosomal synaptic pattern in conjunction with the sex chromosome morphology and pairing behaviour can serve as a reference for the meiotic cell progression from the zygotene stage to the pachytene. The autosomes started terminal synapsis at early zygotene (Z1) and at mid-zygotene (Z2) some of the small bivalents were completely paired. The extension of pairing between the X and the Y chromosome, and the differentiation of their axes, disclosed seven types of sex bivalent (Types 0-VI). The Type 0 sex bivalent occurred in late zygotene (Z3), at which the X and Y axes began terminal synapsis by their short arms. Each one of the pachytene substages, early, mid-, and late, included two sex bivalent types. By early pachytene (P1-P2) the entire Y chromosome was paired with the X axis. Subsequently, progressive desynapsis and differentiation of the sex chromosome axes defined the mid- (P3-P4) and late pachytene substages (P5 P6). At mid-pachytene, the unpaired XY segments were associated end-to-end and showed differing degrees of complexity (thickening, splitting, despiralization and strandedness). These axial complexities were replaced at late pachytene by fine excrescences along the sex chromosome axes, which still formed a short SC stretch. Additionally, an attempt to construct an SC karyotype for the pig is presented. There was general agreement between the autosomal SC karyotype and the autosomal somatic karyotype when comparisons were made, considering the relative lengths and arm ratios of individual chromosome pairs. PMID- 8478211 TI - In situ polymerase chain reaction: toy or tool? PMID- 8478212 TI - Robert Feulgen Prize Lecture. Distribution and role of gap junctions in normal myocardium and human ischaemic heart disease. AB - In the heart, individual cardiac muscle cells are linked by gap junctions. These junctions form low resistance pathways along which the electrical impulse flows rapidly and repeatedly between all the cells of the myocardium, ensuring their synchronous contraction. To obtain probes for mapping the distribution of gap junctions in cardiac tissue, polyclonal antisera were raised to three synthetic peptides, each matching different cytoplasmically exposed portions of the sequence of connexin43, the major gap-junctional protein reported in the heart. The specificity of each antiserum for the peptide to which it was raised was established by dot blotting. New methods were developed for isolating enriched fractions of gap junctions from whole heart and from dissociated adult myocytes, in which detergent-treatment and raising the temperature (potentially damaging steps in previously described techniques) are avoided. Analysis of these fractions by SDS-polyacrylamide gel electrophoresis revealed major bands at 43 kDa (matching the molecular mass of connexin43) and at 70 kDa. Western blot experiments using our antisera indicated that both the 43-kDa and the 70-kDa bands represent cardiac gap-junctional proteins. Pre-embedding immunogold labelling of isolated gap junctions and post-embedding immunogold labelling of Lowicryl-embedded whole tissue demonstrated the specific binding of the antibodies to ultrastructurally defined gap junctions. One antiserum (raised to residues 131-142) was found to be particularly effective for cytochemical labelling. Using this antiserum for immunofluorescence labelling in combination with confocal scanning laser microscopy enabled highly sensitive detection and three-dimensional mapping of gap junctions through thick slices of cardiac tissue. By means of the serial optical sectioning ability of the confocal microscope, images of the entire gap junction population of complete en face viewed disks were reconstructed. These reconstructions reveal the presence of large junctions arranged as a peripheral ring around the disk, with smaller junctions in an interior zone: an arrangement that may facilitate efficient intercellular transfer of current. By applying our immunolabelling techniques to tissue from hearts removed from transplant patients with advanced ischaemic heart disease, we have demonstrated that gap junction distribution between myocytes at the border zone of healed infarcts is markedly disordered. This abnormality may contribute to the genesis of reentrant arrhythmias in ischaemic heart disease. PMID- 8478213 TI - The distribution of oestrogen and progesterone receptors in the human endometrial basal and functional layer during the normal menstrual cycle. An immunocytochemical study. AB - The distribution of oestrogen and progesterone receptors in the human endometrial basal and functional layer during the normal menstrual cycle was investigated by means of an immunocytochemical technique. A cyclic pattern of receptor distribution was observed. The highest concentration of hormone receptors was observed in the basal layer, in accordance with the idea that this layer is the source of endometrial regeneration. PMID- 8478214 TI - Zonal expression of the glucokinase gene in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization. AB - The abundance and zonal distribution of glucokinase (GK) mRNA were studied in rat liver during a normal 12 h day/12 h night rhythm (dark from 1900 to 0700 hours) and during refeeding after 60 h of starvation. Zonation of GK gene expression was examined by in situ hybridization with a radiolabelled cRNA probe and GK mRNA abundance was determined by Northern blot analysis with a digoxigenin-labelled cRNA probe. GK mRNA appeared to be almost homogeneously distributed throughout the whole daily feeding cycle; yet it was predominantly localized in the perivenous and intermediate zone during refeeding after 60 h of starvation. During the daily feeding rhythm, the total amount of GK mRNA increased quickly with the beginning of the feeding period at 1900 hours reaching a maximum at midnight and then decreased continuously to a basal level at noon. Virtually no GK mRNA was detected after 60 h of starvation. Refeeding caused a rapid increase in GK mRNA to a maximum at 2400 hours followed by a decrease to approximately two thirds of the maximum value at 0700 hours. If the homogeneous distribution of GK mRNA during the daily feeding rhythm was real rather than apparent because of too low a sensitivity of the cRNA probe, the present results suggest that during the normal circadian cycle the mainly perivenous distribution of GK enzyme activity and protein is regulated preferentially at a translational level. The findings clearly show that during refeeding after 60 h of starvation the GK distribution is controlled predominantly at a pretranslational level. PMID- 8478216 TI - Allopathic medical research echoes earlier findings in osteopathic medicine. PMID- 8478215 TI - Manipulation, exercise resolve shoulder dysfunction. PMID- 8478217 TI - Immigrants infected with the human immunodeficiency virus (HIV) PMID- 8478218 TI - Using convergent combination therapy, researchers stopped the human immunodeficiency virus (HIV) from reproducing in test tubes. PMID- 8478219 TI - No single test can determine clinical outcome of prostate cancer. PMID- 8478220 TI - Flow cytometric determination of ploidy in prostatic adenocarcinoma and its relation to clinical outcome. AB - Flow cytometry was used to measure the DNA content in paraffin-embedded archival specimens of prostatic adenocarcinoma. The specimens were from 49 patients who were found to have adenocarcinoma of the prostate at the time of transurethral resection of the prostate for bladder outlet obstruction. At initial presentation, 34 of these patients had clinically localized disease and 15 had metastatic disease. The authors studied the relationship of DNA ploidy to clinical stage, histologic grade, disease progression, and duration of survival. Their results indicate that regardless of the clinical stage at presentation, the mean time to disease progression is longer in a patient with a DNA diploid tumor when compared with that in a patient with a DNA aneuploid tumor (18.1 months vs 6.5 months, respectively). Additionally, mean time of survival was longer in a patient with a diploid tumor than in a patient with an aneuploid tumor (31.6 months vs 9.6 months, respectively). PMID- 8478221 TI - Shame and the origin of physician-patient conflict. AB - Shame is a powerful negative emotion that motivates much intrapersonal and interpersonal conflict. The relationship between patient and physician can turn to conflict if the medical environment elicits shame in the patient; conflict arises when the patient externalizes the cause and blames the physician for negative feelings. Patients who suffer from hyperactive and reactive shame responses may require particularly sensitive care. Including the assessment of shame reactivity in the medical history can help identify such persons. Measures that reduce shame should improve compliance and reduce the incidence of malpractice suits. PMID- 8478222 TI - Arranging affiliation agreements and outside rotations. AB - Affiliation agreements are necessary when a sponsoring institution makes arrangements for all or part of the education elements of an internship or residency program to be delivered at another hospital. The sponsoring institution may be a college of osteopathic medicine or an osteopathic hospital. Some basic considerations, which are outlined herein, should be reviewed when the sponsoring institution enters such agreements. Some of these considerations are requirements of the American Osteopathic Association, while others are necessary to avoid later complications. Agreement should be reached on negotiable factors, accepted by both institutions, and then referred for legal review by appropriate authorities. PMID- 8478223 TI - Computed tomography and magnetic resonance imaging of tuberculous meningitis. AB - Tuberculous meningitis usually results from hematogenous seeding of the central nervous system from a primary pulmonary source of infection. Initially, the meningitic process can mimic a flu-like syndrome, followed rapidly by the development of profound neurologic deficits. Computed tomography scanning or magnetic resonance imaging of the head often demonstrates a characteristic pattern of basal cistern involvement with Mycobacterium tuberculosis. The incidence of tuberculous meningitis in the more developed countries has increased during the past 5 years because of the growing number of cases in patients with acquired immunodeficiency syndrome, the spread among the homeless, and the expanding immigrant population. The significant morbidity and mortality rates associated with tuberculous meningitis--generally considered to be a disease of the past--emphasize the need for greater clinical awareness, early diagnosis, and prompt treatment. PMID- 8478224 TI - Group C streptococcal arthritis. AB - Septic arthritis is a common disorder that is rarely caused by group C streptococci. This infectious process usually occurs in patients with a preexisting rheumatologic condition. Treatment consists of intravenous antibiotics, joint aspiration, and physical therapy. Prolonged recovery and septic complications are expected. This report describes a case typical of group C streptococcal arthritis. PMID- 8478225 TI - Another skin manifestation of HIV infection. PMID- 8478226 TI - Long-term results of post-operative radiation therapy following mastectomy with or without chemotherapy in stage I-III breast cancer. AB - PURPOSE: To determine the risk of local-regional failure following post mastectomy radiotherapy and the incidence of complications associated with such treatment. METHODS AND MATERIALS: We retrospectively analyzed the results in 309 patients with Stage I-III invasive breast cancer treated with post-mastectomy radiation therapy between 1975 and 1985. The median radiotherapy dose was 45 Gy in 1.8 to 2.25 Gy fractions. One hundred forty-seven (48%) of the patients received adjuvant systemic chemotherapy with 115 (78%) of these receiving a CMF based or doxorubicin-containing regimen. The median follow-up time of surviving patients was 130 months (range, 28 to 191 months) after mastectomy. RESULTS: Seventeen patients (6%) developed a local-regional failure at an interval of 4 to 87 months after radiotherapy. Moderate or severe complications related to radiotherapy and requiring treatment were uncommon. Symptomatic radiation pneumonitis occurred in four patients (1.3%), arm edema in 18 (5.8%), and brachial plexopathy in 2 (0.6%). CONCLUSION: We conclude that post-operative radiotherapy is a safe and effective means of reducing local-regional failure following mastectomy. The efficacy of post-mastectomy radiotherapy in improving survival should be addressed in new large randomized controlled studies. PMID- 8478227 TI - Sequential transurethral surgery, multiple drug chemotherapy and radiation therapy for invasive bladder carcinoma: initial report. AB - Forty-seven patients with muscle-invasive bladder cancer (T2-T4, Nx, M0) were treated by transurethral resection, followed by 3-4 cycles of combination chemotherapy (methotrexate 30 mg/m2 on days 1, 14; cis-platinum 100 mg/m2 on day 2; vinblastine 3 mg/m2 on days 1, 14; repeated every 21 days), and external beam irradiation (64-66 Gy to the bladder and 40 Gy to the pelvic lymphatics). Complete remission after trans urethral resection and chemotherapy was achieved in 24 out of 45 patients (53%). Cystectomy was performed in patients without complete response to transurethral resection and chemotherapy. The therapy was completed as planned in 45/47 patients. After transurethral resection, chemotherapy, and radiation therapy, biopsy proven complete response was achieved in 62% (28/45); Stage T2T3 in 67% (23/34), Stage T4 in 45% (5/11) of patients. Among 19 patients with positive biopsy findings after transurethral resection and chemotherapy, 14 underwent cystectomy. After follow-up of 4-55 months (median 23 months) 75% (34/45) are alive, 68% (31/45) have had their bladders preserved, and 53% (24/45) are free of the primary tumor. The actuarial survival of all 45 patients is 73%. Moderate nausea and vomiting during treatment were common; severe leukopenia and mucositis were observed in five patients. Late side effects such as miction disorders and diarrhea were predominantly mild. Although the observation period has been too short to allow a definitive evaluation of treatment results, we feel both from the point of bladder preservation and disease-free survival that the presented treatment approach is successful in a majority of T2T3 patients, whereas a large tumor size (T4) renders this treatment less effective. PMID- 8478228 TI - Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12. AB - PURPOSE: This Phase II study was designed to test the tolerance and effectiveness of concurrent cisplatin-radiotherapy in the treatment of invasive bladder cancer. Objectives were to determine toxicity, complete response rate, bladder preservation rate, and survival. METHODS AND MATERIALS: Patients with invasive bladder cancer, clinical Stages T2-4, NO-2 or NX, MO were treated with pelvic radiotherapy 40 Gy in 4 weeks and cisplatin 100 mg/m2 on days 1 and 22. Complete responders were given an additional 24 Gy bladder boost plus a third dose of cisplatin; patients with residual tumor after 40 Gy were assigned radical cystectomy. RESULTS: The complete remission rate following cisplatin and 40 Gy for evaluable cases was 31/47 (66%). Acute toxicity was acceptable with only two patients not completing induction therapy. Patients with poorly differentiated tumors were more likely to achieve complete remission. Of fully evaluable patients, 28/42 (67%) achieved complete remission with induction therapy, 11 remain continuously in remission, and eight have relapsed with bladder as the only site of failure. Five of these eight cases relapsed with noninvasive tumor. Of the 14 patients who failed to achieve complete remission, only three remain disease-free. Median survival is not reached, with 17/42 (19/48) deaths reported. Actuarial survival is 64% at 3 years. CONCLUSION: This combined cisplatin radiotherapy regimen was moderately well-tolerated and associated with tumor clearance in 66% of patients treated. Isolated bladder recurrences with invasive carcinoma are infrequent. Better definition of pretreatment selection criteria is needed if combined modality treatment is to achieve disease control and organ preservation for patients with bladder cancer. PMID- 8478229 TI - Preoperative concurrent 5-fluorouracil infusion, mitomycin C and pelvic radiation therapy in tethered and fixed rectal carcinoma. AB - PURPOSE: This is a Phase I/II study of preoperative concurrent radiation and chemotherapy in tethered and fixed rectal carcinoma. This study examined the curative resectability, the acute toxicities during chemo-radiation and the surgical complications. METHODS AND MATERIALS: Between 1986 and 1990, 46 patients were treated with preoperative pelvic radiation (4000 cGy in 20 fractions in 4 weeks), 5-Fluorouracil infusion (20 mg/m2, days 1-4 and 15-18) and Mitomycin C (8 mg/m2, day 1). This was followed by surgery 6 to 8 weeks later. 30 patients had tethered tumors and 16 patients had fixed tumors. RESULTS: After preoperative chemo-radiation, 41 patients (89%) underwent curative resection. Two patients (4%) had no residual tumor found (T0N0M0). Seven patients (15%) had nodal metastases. Two patients developed grade 3 neutropenia (WBC = 1-2 x 10(9)/L) during chemo-radiation. Five patients had delay in perineal wound healing. One patient had an anastomotic leak. Four patients developed stomal stenosis which required surgical revision. The 2-year actuarial survival was 73%. The 2-year local relapse rate was 16%. Patients with fixed carcinoma had a higher incidence of local failure (38% vs. 10%) and the difference was statistically significant (p = 0.0036). The 2-year distant failure rate was 41%, and the rates were similar for both tethered and fixed carcinomas. CONCLUSION: Preoperative pelvic radiation, chemotherapy and surgery could achieve a curative resection rate of 89% in tethered and fixed rectal carcinomas. However, distant metastases remained the major cause of failure. PMID- 8478230 TI - Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. AB - PURPOSE: A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases. METHODS AND MATERIALS: The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo. RESULTS: One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor makers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89. CONCLUSIONS: It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality of-life and need for analgesic support in this group of patients. PMID- 8478231 TI - Radiation dose to the lens and cataract formation. AB - PURPOSE: To determine the radiation tolerance of the lens of the eye and the incidence of radiation-induced lens changes in patients treated by fractionated supervoltage radiation therapy for orbital tumors. METHODS: Forty patients treated for orbital lymphoma and pseudotumour with tumour doses of 20-40 Gy were studied. The lens was partly shielded using lead cylinders in most cases. The dose to the germinative zone of the lens was estimated by measurements in a tissue equivalent phantom using both film densitometry and thermoluminescent dosimetry. Ophthalmological examination was performed at 6 monthly intervals after treatment. RESULTS: The lead shield was found to reduce the dose to the germinative zone of the lens to between 36-50% of the tumor dose for Cobalt beam therapy, and to between 11-18% for 5 MeV x-rays. Consequently, the len doses were in the range 4.5-30 Gy in 10-20 fractions. Lens opacities first appeared from between 3 and 9 years after irradiation. Impairment of visual acuity ensued in 74% of the patients who developed lens opacities. The incidence of lens changes was strongly dose-related. None was seen after doses of 5 Gy or lower, whereas doses of 16.5 Gy or higher were all followed by lens opacities which impaired visual acuity. The largest number of patients received a maximum lens dose of 15 Gy; in this group the actuarial incidence of lens opacities at 8 years was 57% with visual impairment in 38%. CONCLUSION: The adult lens can tolerate a total dose of 5 Gy during a fractionated course of supervoltage radiation therapy without showing any changes. Doses of 16.5 Gy or higher will almost invariably lead to visual impairment. The dose which causes a 50% probability of visual impairment is approximately 15 Gy. PMID- 8478232 TI - Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer. AB - PURPOSE: We performed a Phase I trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5 FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. METHODS AND MATERIALS: Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy, was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7-16 months). RESULTS: Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153,000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. CONCLUSIONS: Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, we do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate we remain encouraged with this approach. PMID- 8478233 TI - Determination of the radiation sensitivity of the stromal cells in the murine long-term bone marrow culture by measuring the induction and rejoining of interphase chromosome breaks. AB - PURPOSE: To determine the radiosensitivity of bone marrow stromal cells, the rate of interphase chromosome breakage and rejoining of stromal cells in the murine long term bone marrow culture and of human skin fibroblasts were compared. METHODS AND MATERIALS: The cells were irradiated with doses up to 6 Gy and repair times up to 6 hr were investigated. After induction of premature chromosome condensation by fusing the cells with mitotic HeLa cells, the number of interphase chromosome fragments was counted. RESULTS: The number of radiation induced breaks was found to be not significantly different for both cell types with 6.16 +/- 0.26 breaks per Gray for the fibroblasts and 5.96 +/- 0.20 breaks per Gray for the stromal cells. A significant difference was observed in the repair rate. The fibroblasts rejoined 39.6% of the breaks induced initially during the first hour after irradiation and 5.6 +/- 1.84 breaks remained unrejoined after 6 hr, while the stromal cells were able to rejoin 63.2% in 1 hr and had 2.05 +/- 0.07 breaks unrejoined after 6 hr. CONCLUSION: If the well substantiated assumption is made, that the capacity to repair DNA double strand breaks or interphase chromosome breaks is correlated with the cellular radiosensitivity, this finding indicate, that murine bone marrow stromal cells are more radioresistant than human skin fibroblasts. PMID- 8478234 TI - The relative biological effectiveness of ytterbium-169 for low dose rate irradiation of cultured mammalian cells. AB - PURPOSE: An important step in the development of 169Yb as a new brachytherapy source is to determine its biological effectiveness relative to other commonly used radioisotopes. The purpose of this paper is to determine the relative biological effectiveness of 169Yb, with respect to 60Co, for a range of low dose rates. METHOD AND MATERIALS: The relative biological effectiveness of photon radiation from encapsulated 169Yb was determined by exposing Chinese hamster ovary cells, in exponential growth, to graded doses of radiation from either 169Yb or 60Co. Clonogenic cell survival was determined for continuous low dose rates ranging from 6.5 cGy/hr to 52 cGy/hr. RESULTS: The relative biological effectiveness of 169Yb, with respect to 60Co, was determined to be 1.2 +/- 0.3 and did not vary significantly over the dose-rate range from 13 cGy/hr to 50 cGy/hr. An inverse dose-rate effect was observed, but only for 60Co irradiation at 8.9 cGy/hr. Therefore, relative biological effectiveness values could not be determined reliably for dose rates less than 13 cGy/hr. CONCLUSIONS: We have established that 169Yb is approximately 20% more effective than 60Co in vitro. It is hoped that this study will guide the introduction of 169Yb into clinical brachytherapy practice. PMID- 8478235 TI - Cumulative minutes with T90 greater than Tempindex is predictive of response of superficial malignancies to hyperthermia and radiation. AB - PURPOSE: To better define thermal parameters related to tumor response in superficial malignancies treated with combined hyperthermia and radiation therapy. METHODS AND MATERIALS: Patients were randomized to receive one or two hyperthermia treatments per week with hyperthermia given during each week of irradiation. Hyperthermia was given for 60 min with treatments begun within 1 hr following irradiation. Power was increased to patient tolerance or normal tissue temperature of 43.0 degrees C. Irradiation was generally given 5 times per week with doses prescribed to normal tissue tolerance (generally 24-70 Gy at 1.8-2.5 Gy per fraction). Multipoint thermometry was used with temperatures obtained every 5 min. RESULTS: One hundred eleven individual treatment fields containing 1 or more tumor nodules were completely evaluable. The complete and overall response rates were 46% and 80%, respectively. Forty-one percent of all treatment fields (51% of responding lesions) remained controlled at 2 years. Multivariate analysis revealed that the cumulative minutes that the temperature achieved by 90% of the measured tumor sites (T90) was > or = 40.0 degrees C, tumor histology, tumor volume, and radiation dose were significantly associated with complete tumor response. The complete response rate was not significantly affected by the number of hyperthermia treatments given per week. The incidence of clinically significant complications was low. CONCLUSIONS: These results support the usefulness of the cumulative minute system in describing time-temperature relationships. The significance of thermal variables with regard to tumor response strongly supports the contention that hyperthermia can be a useful adjunct to irradiation for the local control of cancer. PMID- 8478236 TI - Beam shaping for microwave waveguide hyperthermia applicators. AB - PURPOSE: Hyperthermia treatments commonly use single element microwave waveguide applicators. The microwave beam patterns produced by these applicators are often non-uniform. As a result, hot spots are formed in the heated tissue and therapeutic temperatures are reached in only small areas of the treatment field. We have constructed new coupling boluses that improve the heating patterns of external microwave applicators. METHODS: The microwave beam transmitted through the bolus is modified by microwave absorbing saline/gelatin pads. The pads can be designed to result in a uniform heating pattern over a large area or alternatively, complex heating patterns can be generated for specific clinical applications. An analysis of the effect of bolus design parameters on microwave absorption patterns is presented. The heating patterns of the MA-100 and MA-120 microwave waveguide applicators have been measured in muscle and fat phantom materials with both the manufacturer's boluses and the new boluses. RESULTS: In the case of the MA-100, the area above the 70% heating level measured in a muscle phantom was increased by a factor of 2.3 by an absorbing pad bolus. Similarly, the heating area of the MA-120 was increased by a factor of 2.6 by an absorbing pad bolus. The boluses were tested in a clinical setting by measuring tissue temperature profiles in patients under different bolus arrangements. The area over which therapeutic temperature was achieved was increased considerably when the absorbing bolus was used. A second bolus was designed for the MA-120 to produce a ring heating pattern for the treatment of a breast cancer patient who had developed recurrences at the periphery of a skin graft. The heating pattern produced in a muscle phantom is compared with tissue temperature profiles measured during the hyperthermia treatment of this patient. CONCLUSIONS: Microwave absorbing filters using saline pads significantly improve the heating patterns of microwave waveguide hyperthermia applicators. This improvement was confirmed in clinical application where much greater areas of homogeneous heating were observed. The technology was extended to produce complex heating patterns for special clinical applications. PMID- 8478237 TI - Dynamic field shaping for stereotactic radiosurgery: a modeling study. AB - PURPOSE: This work assesses the relative field shaping advantages of dynamic field shaping devices for stereotactic radiosurgery using a linear accelerator. METHODS AND MATERIALS: We selected 43 intracranial tumors (2.0-4.2 cm maximum dimension, 1.5-25.5 cc tumor volume) out of the first 64 intracranial tumors treated with radiosurgery at the Joint Center for Radiation Therapy. We modeled five field shaping devices, each including a fixed auxiliary circular collimator: (a) fixed circular collimator alone; (b) two independent parallel jaws; (c) four independent rectangular jaws; (d) four independent rotatable jaws; and (e) "ideal" multileaf collimator. We adjusted the model parameters until the minimum target isodose was 80% of the dose delivered to isocenter. We defined the treatment volume ratio as the target volume divided by the treatment volume (volume receiving at least the minimum target dose). We used the treatment volume ratio to compare the five models and the actual patient treatments. RESULTS: For 34 tumors originally treated with one isocenter, the median Treatment Volume Ratio was higher for all of the device models except the fixed circular collimator compared to the actual patient treatments. For the nine tumors originally treated with multiple isocenters, the median Treatment Volume Ratio for the actual multiple isocenter treatments was similar to that for two parallel jaws, four rectangular jaws and four rotatable jaws. Only the median "ideal" collimator treatment volume ratio was higher for these nine tumors. CONCLUSION: Simple field shaping devices have approximately 50% of the conformal advantage of an "ideal" multileaf collimator. Approximately 50% of typical radiosurgical tumors between 2 and 4 cm have field shaping advantages which exceed the geometrical uncertainties inherent in linear accelerator radiosurgery treatments. The three models, two parallel, four rectangular, or four rotatable independent jaws would improve current linear accelerator technology by providing homogeneous doses with equivalent field shaping for most tumors originally treated with inhomogeneous multiple isocenter plans (6/9 tumors in the current series). PMID- 8478238 TI - Follow-up thallium-201 scintigraphy after mantle field radiotherapy for Hodgkin's disease. AB - PURPOSE: Assessment of the long-term cardiac effects of mediastinal radiotherapy for Hodgkin's disease, by Thallium scintigraphy. METHODS AND MATERIALS: 32 patients (14 males and 18 females) who underwent mantle field radiotherapy for Hodgkin's disease were included in this study. Twenty patients received 4 fractions of 2.5 Gy per week and 12, five fraction of 2 Gy per week, delivered on alternate days. All the patients, except three, performed exercise testing electrocardiogram and Thallium-201 tomoscintigraphy. The average time interval from completion of treatment to the study was 7 years (range 3-13 years). No patients had clinical symptoms of cardiac disease. Mean age at the time of the study was 35 years (range 23-48 years). RESULTS: Two electrocardiograms revealed left bundle branch block and the patients were excluded from the study. Only one out of 27 exercise electrocardiograms was abnormal in a patient with mitral valve prolapse, who was also excluded from the study. Twenty-six scintigraphies were evaluable. Twenty-two (85%) were clearly abnormal with partial or complete redistribution on delayed images. The anterior region was affected in 19 of these cases (86%). Four explorations were undoubtedly normal. Coronary angiography was not performed for ethical reasons in these asymptomatic patients. CONCLUSION: Despite possible false positive tests, the high rate of abnormality (85%) in this small series is striking. These preliminary data justify larger studies and a close long-term follow-up of these patients. PMID- 8478239 TI - Malignant glioma--timing of response to radiation therapy. AB - PURPOSE: The response of malignant gliomas to radiation was examined retrospectively in 71 patients with newly diagnosed supratentorial malignant gliomas. Questions asked included frequency, timing and clinical significance of response. METHODS AND MATERIALS: After surgery, all were treated with whole brain plus boost radiotherapy followed 8 weeks later by chemotherapy. The rate, degree, and timing of response to radiation were determined by comparing postoperative, end of radiation, and prechemotherapy CT scans on each patient. RESULTS: Postoperative residual tumor was evident on 63/71 postoperative scans. Twenty-two of 63 tumors (35%) had a partial or complete response to radiation. Twenty (32%) had responded by the end of radiation; 17 maximally. Six to 8 weeks later, three responding tumors had responded further and two previously stable ones had begun to respond. Only three tumors (5%) responded completely. A greater proportion of anaplastic gliomas than glioblastomas responded to radiation (52% vs. 26%). Protracted or delayed responses were only observed in patients with anaplastic glioma. Patients who responded to radiation did not live significantly longer than non-responders. However, tumor progression prior to chemotherapy was associated with significantly shorter survival. CONCLUSION: This CT scan-based analysis demonstrates that malignant gliomas are only moderately radioresponsive tumors and also demonstrates that response to radiation, if it is going to occur, is usually evident by the end of treatment. PMID- 8478240 TI - Autoradiography for iodine-125 seeds. AB - To study the interior design of model 6702 and 6711 iodine-125 seeds contact autoradiographs were performed using mammography film. Improved resolution was obtained using a pin-hole camera with a hole of 0.1 mm x 0.1 mm. With these techniques, qualitative determination of the relative activity distribution within each seed was possible. The number of the activated resin spheres and the positions of the centers of these spheres can be exactly determined. A model calculation shows, that variations in the arrangement of the activated spheres within a seed have a moderate influence on the dose distribution at source distances below 10 mm. Knowing the exact source configuration may be useful when comparing dose calculations with measured data for model 6702 125I seeds which are currently employed in ophthalmic plaque and implant therapy of other tumors. PMID- 8478241 TI - Volumetric analysis of small bowel displacement from radiation portals with the use of a pelvic tissue expander. AB - PURPOSE: Many techniques and devices have been used in an attempt to minimize gastrointestinal morbidity of pelvic irradiation. The value of a temporary intrapelvic tissue expander to displace small bowel from pelvic radiotherapy fields was analyzed by comparing volumetric treatment parameters of patients with and without such a device. METHODS AND MATERIALS: Between 1983 and 1991, 77 patients with a diagnosis of endometrial (n = 35), colorectal (n = 41), or anal carcinoma (n = 1) received adjuvant postoperative radiotherapy after undergoing treatment planning simulation with the use of small bowel oral contrast medium. Fourteen of these patients underwent surgical placement of a temporary intrapelvic tissue expander prior to radiotherapy, and 63 patients did not. Small bowel volume within the treatment portals was measured for both initial pelvic and conedown fields for all cases, and compared between the two patient groups. RESULTS: The volume of small bowel within the initial pelvic fields receiving full dose irradiation was significantly less among patients with a tissue expander. For patients with a tissue expander, mean volume receiving full dose irradiation was 25 cm3 (median 0 cm3, range 0-297 cm3), whereas the corresponding volume was 239 cm3 (median 181 cm3, range 0-943 cm3) without a tissue expander (p < .0001). A similar reduction of irradiated small bowel volume was noted in the conedown fields with the use of a tissue expander (p = .07). Volumes receiving less than full dose irradiation were also less within the initial pelvic (p = .0001) and conedown (p = .002) fields with a tissue expander. Multivariate analysis of patient and treatment-related parameters showed the use of a tissue expander to be the only factor correlated with decreased small bowel volume within the treatment field (p = .003). Morbidity related to placement and removal of the tissue expander was acceptable. Acute radiation-related morbidity was significantly less in patients irradiated with a tissue expander in place (p < .001). CONCLUSIONS: Placement of an intrapelvic tissue expander was correlated with decreased small bowel volume within the radiotherapy treatment field. Diminished radiation-induced acute gastrointestinal morbidity was noted with use of a tissue expander. PMID- 8478242 TI - Cost accounting in radiation oncology: a computer-based model for reimbursement. AB - PURPOSE: The skyrocketing cost of medical care in the United States has resulted in multiple efforts in cost containment. The present work offers a rational computer-based cost accounting approach to determine the actual use of resources in providing a specific service in a radiation oncology center. METHODS AND MATERIALS: A procedure-level cost accounting system was developed by using recorded information on actual time and effort spent by individual staff members performing various radiation oncology procedures, and analyzing direct and indirect costs related to staffing (labor), facilities and equipment, supplies, etc. Expenditures were classified as direct or indirect and fixed or variable. A relative value unit was generated to allocate specific cost factors to each procedure. RESULTS: Different costs per procedure were identified according to complexity. Whereas there was no significant difference in the treatment time between low-energy (4 and 6 MV) or high-energy (18 MV) accelerators, there were significantly higher costs identified in the operation of a high-energy linear accelerator, a reflection of initial equipment investment, quality assurance and calibration procedures, maintenance costs, service contract, and replacement parts. Utilization of resources was related to the complexity of the procedures performed and whether the treatments were delivered to inpatients or outpatients. In analyzing time motion for physicians and other staff, it was apparent that a greater effort must be made to train the staff to accurately record all times involved in a given procedure, and it is strongly recommended that each institution perform its own time motion studies to more accurately determine operating costs. Sixty-six percent of our facility's global costs were for labor, 20% for other operating expenses, 10% for space, and 4% for equipment. Significant differences were noted in the cost allocation for professional or technical functions, as labor, space, and equipment costs are higher in the latter. External beam treatment-related procedures accounted for more than 50% of all technical and professional revenues, simulation for 8% to 10%, and other physics/dosimetry procedures for 11% to 14% of revenues. Some discrepancies were identified between the actual cost and level of reimbursement of various procedures. Details are described in the manuscript. CONCLUSION: It is imperative to develop an equitable reimbursement system for radiation oncology services, based on cost accounting and other measures that may enhance productivity and reduce the cost per procedure unit, while at the same time preserving the highest quality of service provided to patients. PMID- 8478243 TI - Radiotoxic model for three-dimensional treatment planning. Part 1: Theoretical basis. AB - Since recent treatment planning systems calculate volumetric dose distribution, an objective evaluation of potential toxicity in the main critical organs may be helpful in treatment optimization. Modeling the toxicity of radiotherapy must at least account for: (a) specific risks in every critical organ; (b) total dose and dose per fraction; (c) partial irradiation of critical organs; (d) heterogeneous dose distribution. The Radiation Damage Factor formula is aimed at estimating the delayed toxicity of a given treatment plan on every critical organ concerned. The formulation uses a double exponential function: RDF = 100 e-Ke-(a+bd)DVc, where: D is the total dose, and d the dose per fraction; a and b are coefficients representing the radiosensitivity of the critical organ, according to the linear quadratic model, with a/b = alpha/beta. K represents the theoretical critical unit content of the organ, these critical units being groups of functionally related stem cells. The avoidance of a complication depends on the ability of surviving critical units to preserve organ function. V is the ratio:irradiated volume/total volume of the organ. Exponent c accounts for tissue organization: c is equal to or near 1 in "parallel organs" like the liver or the lung, where localized hot spots are tolerated; c is lower in "series organs" like the spinal cord where hot spots, even in a small portion, are dangerous. Heterogeneous irradiation, summarized by dose cumulative-volume histograms, is accounted for by calculating step by step the dose D' considered as having an equivalent effect when given in the largest irradiated volume ratio. Preliminary calibration of the RDF formula is attempted for radiation myelitis and radiation hepatitis. PMID- 8478244 TI - Hodgkin's disease with bulky mediastinal involvement. PMID- 8478245 TI - Pre-operative chemoradiation for advanced rectal cancer. PMID- 8478246 TI - Fatal hemoptysis: complication or failure of treatment. PMID- 8478247 TI - Regarding predictive role of TDF values in late rectal recto-sigmoid complications in irradiation treatment of cervix cancer. PMID- 8478248 TI - A "reappraisal" of the LQ model for the understanding of dose-fractionation in radiotherapy. PMID- 8478249 TI - Radiation-recall. PMID- 8478250 TI - Psychophysiology and social events. PMID- 8478251 TI - Psychophysiology and the changing world. PMID- 8478252 TI - In commemorating the 10th anniversary of the International Organization of Psychophysiology. PMID- 8478253 TI - Psychophysiologists and the AIDS epidemic: can we help? PMID- 8478254 TI - Terpestacin, a new syncytium formation inhibitor from Arthrinium sp. AB - Terpestacin, a new antibiotic which inhibits syncytium formation, was isolated from Arthrinium sp. FA1744 (ATCC 74132). The structure of terpestacin was elucidated as a bicyclic sesterterpene on the basis of spectroscopic data and chemical derivatization. PMID- 8478255 TI - 5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. I. Taxonomy and fermentation of the producing organism and biological activity. AB - The ardeemins are a new family of secondary metabolites produced by submerged fermentation of a fungus which was isolated from a soil sample collected in Brazil. Based on taxonomic studies, the producing culture was identified as Aspergillus fischeri var. brasiliensis strain AB 1826M-35. 5-N-Acetylardeemin potentiated the cytotoxicity of the anticancer agent vinblastine in multidrug resistant human tumor cells. PMID- 8478256 TI - 5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. II. Isolation and elucidation of the structure of 5-N acetylardeemin and two congeners. AB - A family of novel compounds has been detected and isolated following an assay for the attenuation of multiple drug resistance in tumor cells from the fermentation broth and mycelia of a strain of Aspergillus fischeri which we have designated var. brasiliensis. The structures of three components were determined employing 1 D and 2-D homonuclear and heteronuclear NMR spectroscopy and mass spectrometry. The structure of 5-N-acetylardeemin was confirmed by single crystal X-ray diffraction. These compounds are most closely structurally related to asperlicin E1). PMID- 8478257 TI - Pradimicins L and FL: new pradimicin congeners from Actinomadura verrucosospora subsp. neohibisca. AB - Pradimicin L, a new congener of pradimicin A having the D-glucosyl-D-thomosamine moiety at the C-5 position, was isolated from Actinomadura verrucosospora subsp. neohibisca subsp. nov. The structure of pradimicin L was deduced to be N [[(5S,6S)-5-O-[4,6-dideoxy-4-(methylamino)-3-O-(beta-D-glucopyranosyl) - beta-D galactopyranosyl]-5,6,8,13-tetrahydro-1,5,6,9,14-pentahydroxy-11- methoxy-3 methyl-8,13-dioxobenzo[a]naphthacene-2-yl]carbonyl ]-D-alanine by MS and NMR spectrometry and degradation studies. Pradimicin FL which has the D-serine moiety instead of D-alanine was produced by directed biosynthesis in D-serine supplemented medium. Pradimicins L and FL have a broad spectrum of in vitro antifungal activity. Pradimicin L was equiactive to pradimicin A and pradimicin FL was more active than pradimicin L. PMID- 8478258 TI - Pradimicins FS and FB, new pradimicin analogs: directed production, structures and biological activities. AB - Exogenous addition of D-serine to Actinomadura spinosa AA0851 resulted in directed production of pradimicin FS, a new D-serine analog of pradimicin S, together with pradimicin FB. Pradimicin FS was produced in higher yields by derivation of ferrous sulfate-resistant strains from strain AA0851. Pradimicin FB, a minor product, was identified as deglucosylpradimicin FL. Pradimicin FS was equivalent to pradimicin S in syncytium formation inhibition activity and in vitro and in vivo antifungal activities. PMID- 8478259 TI - Biosynthesis of the pradimicin family of antibiotics. I. Generation and selection of pradimicin-nonproducing mutants. AB - Germinated spores of Actinomadura verrucosospora subsp. neohibisca E-40, a high pradimicins producer, were mutagenized by N-methyl-N'-nitro-N-nitrosoguanidine and/or UV treatment. Thirty-seven mutants which did not produce pradimicin were selected to test for cosynthesis ability, and classified into nine classes. On the basis of their cosynthesis ability and bioconversion results, we concluded that strain JN-213 (class III) was a true converter and that strains JN-219 (class IV), JN-47 (class V) and JNU-46 (class VI) were secretors accumulating biosynthetic intermediates of pradimicin, and that strains JN-59 (class VII), JN 58 (class VIII) and JN-207 (class IX) were producers of shunt metabolites of pradimicin biosynthesis. TLC and HPLC analyses of the fermentation broths of individual strains showed that 8 new compounds were produced along with pradinone I, pradimicinone I, 11-O-demethylpradimicinone II and 7-O-methylpradimicinone II. PMID- 8478260 TI - Biosynthesis of the pradimicin family of antibiotics. II. Fermentation, isolation and structure determination of metabolites associated with the pradimicins biosynthesis. AB - Ten metabolites produced by 4 mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40, a high pradimicins producer, were isolated and their structures were determined. Strain JN-219 produced 3 novel analogs of the pradimicin A aglycone, i.e. 11-O-demethyl-7-methoxypradinone II and 11-O demethylpradinones I and II together with a known aglycone analog, pradinone I, while the metabolites from strain JN-47 were determined to be 2 new aglycone analogs, 11-O-demethylpradimicinone I and 11-O-demethyl-7-methoxypradimicinone II and a known aglycone analog, 11-O-demethylpradimicinone II (11dM-PMN II). Products of strain JN-207 were identified as 11-O-demethyl-6-deoxypradinone I and 11dM-PMN II. Interestingly, a new pradimicin analog, 7-hydroxypradimicin A was isolated from strain JN-58 together with a new aglycone analog, pradimicinone II and 11dM-PMN II. None of these metabolites showed antifungal activity. PMID- 8478261 TI - Biosynthesis of the pradimicin family of antibiotics. III. Biosynthetic pathway of both pradimicins and benanomicins. AB - The biosynthetic pathway of the pradimicin-benanomicin family of antibiotics was investigated by using sinefungin and blocked mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40 (a high pradimicin producer) or Actinomadura sp. AB1236 (a benanomicin producer). Addition of sinefungin to strain E-40, pradimicin A aglycone-producing mutant or strain AB1236 inhibited the formation of 11-O-demethyl-7-methoxypradinone II (11dM-7M-PN II), resulting in the accumulation of 11-O-demethylpradimicinone II and pradimicinone II. By feeding pradimicin A aglycone and its analogs to mutants blocked early in pradimicin or benanomicin biosynthesis, the following results were obtained: 11-O demethylpradinone II, 11dM-7M-PN II 11-O-demethylpradinone I, 11-O demethylpradimicinone I and pradimicinone I were converted to pradimicin A or benanomicin A; the remaining 6 aglycone analogs were not incorporated into the antibiotics. Pradimicin B, dexylosylpradimicin C and dexylosylbenanomicin A were converted to pradimicin A, pradimicin C and benanomicin A, respectively. A biosynthetic pathway for the antibiotics is proposed. PMID- 8478262 TI - Autoregulation of carbapenem biosynthesis in Erwinia carotovora by analogues of N (3-oxohexanoyl)-L-homoserine lactone. AB - N-(3-Oxohexanoyl)-L-homoserine lactone (HSL) (I) is the autoregulator controlling carbapenem antibiotic biosynthesis in Erwinia carotovora ATCC 39048. The chemical synthesis and biological evaluation of analogues of HSL are described. These include alterations of chirality, side-chain modifications, ring size and ring hetero atom. A number of compounds are reported which are capable of restoring the phenotype to a HSL negative mutant but at higher concentrations than HSL. A factor, the autoregulator of streptomycin biosynthesis in Streptomyces griseus, was not active as an inducer of carbapenem biosynthesis in E. carotovora. PMID- 8478263 TI - Studies on the mode of antifungal action of pradimicin antibiotics. II. D mannopyranoside-binding site and calcium-binding site. AB - Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium. The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation. The stereospecific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety. Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test. PMID- 8478264 TI - Studies on the mode of antifungal action of pradimicin antibiotics. III. Spectrophotometric sequence analysis of the ternary complex formation of BMY 28864 with D-mannopyranoside and calcium. AB - Sequence of reactions in the process of ternary complex formation of BMY-28864 with D-mannopyranoside and calcium was spectrophotometrically determined under more strict analytical conditions using metal-free preparations of sugars and the pradimicin derivative at a bandpass slit width of 1 nm. In the first phase of ternary complex formation, BMY-28864 stereospecifically recognized and bound to D mannopyranoside in the absence of calcium, which was revealed by a visible absorption maximum shift of ca. 8 nm. Subsequently, the BMY-28864-D mannopyranoside conjugate reacted with calcium to yield the ternary complex, which was detected by an additional visible absorption maximum shift of ca. 8 nm. When the three components were mixed at the same time, both phases simultaneously occurred to produce the ternary complex which was accompanied by a visible absorption maximum shift of 16 nm in total. Based on this two-phased reaction sequence, the mechanism of ternary complex formation of BMY-28864 with D mannopyranoside and calcium was reexamined in details. Terminal D-mannopyranoside was confirmed to be essential as BMY-28864-specific sugar receptor by in vitro analysis and animal cell experiments. While calcium, strontium and cadmium behaved similar in the in vitro ternary complex formation, the yeast and animal cell experiments showed that only calcium played a dual role as a base in the ternary complex formation and as an effector in physiological disturbances leading to cell death. PMID- 8478265 TI - Implication of cohesive binding of a macrolide antibiotic, rokitamycin, to ribosomes from Staphylococcus aureus. AB - In a previous paper we reported that rokitamycin (RKM) which killed some types of RKM-susceptible staphylococci bound cohesively to ribosomes obtained from such bacteria whereas other macrolides such as erythromycin and josamycin, which are generally known to be bacteriostatic, bound to these ribosomes only reversibly. From this observation, we speculated that such cohesive binding of RKM to certain ribosomes probably resulted in cell killing (Endou, K. et al., FEMS Microbiology Letters, 72: 93-96, 1990). However, this speculation was based only on circumstantial evidence and we did not show directly that reversible binding of RKM to ribosomes from other strains would bring about bacteriostasis only. A clinically isolated strain. Staphylococcus aureus S704, was found to be susceptible to RKM, mycinamicin and tylosin as well as lincosamide and streptogramin type B antibiotics but not to other macrolides (erythromycin, josamycin, rosamicin, etc.). RKM showed bacteriostatic, but not bactericidal activity, on the strain. Determinant(s) responsible for the bacteriostatic phenotype was transferred into strain NCTC8325 using bacteriophage 80L2; the obtained transductant was referred to as strain 8325MMT7. The drug bound reversibly, not cohesively, to the ribosomes from both strains S704 and 8325MMT7, confirming our earlier hypothesis that rokitamycin can cause bacteriostasis or cell death depending upon whether it binds reversibly or cohesively to the ribosomes of a given strain. PMID- 8478266 TI - Synthesis and antifungal selectivity of new derivatives of amphotericin B modified at the C-13 position. AB - The syntheses of the first amphotericin B derivatives to be modified solely at the C-13 hemiketal position are described. Selective functionalisation at this position is facilitated by use of the allyl ester as a C-16 carboxylate protecting group on the amphotericin B nucleus. In in vitro tests all compounds showed markedly reduced haemolytic activity against mammalian erythrocytes while two of the novel 13-alkoxy derivatives retained good antifungal activity. PMID- 8478267 TI - Synthesis and antifungal activities of pradimicin A derivatives modification of the alanine moiety. AB - Chemical modifications of the carboxyl group in the alanine moiety of pradimicin A were performed and in vitro and in vivo antifungal activities of the derivatives were examined in comparison with those of pradimicin A. The amide derivatives showed activities comparable to pradimicin A, indicating that the free carboxyl group can be modified without impairing the antifungal activity. PMID- 8478268 TI - Synthesis and antifungal activities of alanine-exchanged analogs of pradimicin A. AB - A series of pradimicin analogs were designed and synthesized to investigate the effect of the amino acid side chain on the antifungal activity. The alanine exchanged analogs (3a approximately 3q) were synthesized from 4'-N-Cbz-pradimic acid by coupling with appropriate amino acids or their equivalents followed by deblocking. All the D-alpha-amino acid derivatives except D-proline analog, 3k retained the antifungal activity. PMID- 8478269 TI - Pradimicin Q, a new pradimicin aglycone, with alpha-glucosidase inhibitory activity. PMID- 8478270 TI - Analysis of the nucleotide sequence of fmrT encoding the self-defense gene of the istamycin producer, Streptomyces tenjimariensis ATCC 31602; comparison with the squences of kamB of Streptomyces tenebrarius NCIB 11028 and kamC of Saccharopolyspora hirsuta CL102. PMID- 8478271 TI - Microbial conversion of milbemycins: 28-hydroxylation of milbemycins by Amycolata autotrophica. PMID- 8478272 TI - Biological activities of novel polyether antifungals, gambieric acids A and B from a marine dinoflagellate Gambierdiscus toxicus. PMID- 8478273 TI - Anticoccidial activity of salinomycin derivatives. PMID- 8478274 TI - New 2''-amino derivatives of arbekacin, potent aminoglycoside antibiotics against methicillin-resistant Staphylococcus aureus. PMID- 8478275 TI - A synthetic opioid peptide increases plasma growth hormone and prolactin in Holstein calves. AB - The effect of the synthetic opioid agonist D-Ala2,N-Me-Phe4,Met(O)5-ol enkephalin (DAMME) on plasma growth hormone (GH) and prolactin (PRL) concentrations in Holstein heifer calves was investigated in this study. The possible site of action of DAMME was determined by pretreating calves with an opioid antagonist that crosses the blood-brain barrier poorly if at all (N-methyl levallorphan methane sulphonate [MLM]) or one that crosses readily (naloxone [NAL]). All calves were assigned to one of three treatment groups: 1) pretreatment with saline, 2) pretreatment with NAL, or 3) pretreatment with MLM. All groups were injected with DAMME 30 min after pretreatments. Plasma PRL increased after injection of DAMME in calves pretreated with saline. Prolactin concentrations were not different before and after injection of DAMME in calves pretreated with either NAL or MLM. Plasma GH increased after injection of DAMME in saline- and MLM-pretreated calves but was unchanged in NAL-pretreated calves. These data show that peripherally administered DAMME increases plasma GH and PRL in Holstein heifer calves and suggest that DAMME mediates GH release through receptors located somewhere inside the blood-brain barrier, but it can induce PRL secretion at a site located outside the barrier. PMID- 8478276 TI - Effects of supplemental protein source on passage of nitrogen to the small intestine, nutritional status of pregnant ewes, and wool follicle development of progeny. AB - Rambouillet wethers, surgically fitted with ruminal and duodenal cannulas, were used to determine the influence of substituting soybean meal (SBM) with blood meal (BM) in grass hay diets (8.0% CP) on N flow to the small intestine. Treatments were arranged in a 3 x 4 Latin square design and included diets (10.6% CP) supplemented with SBM; 2/3 SBM:1/3 BM; 1/3 SBM:2/3 BM; or BM. Ruminal NH3 N concentration decreased linearly (P = .03) as BM replaced SBM; however, feeding BM did not affect (P > .10) the total N, microbial N, or nonammonia N flows to the small intestine. A second experiment was conducted to determine the influence of substituting SBM with BM on ewe BW and condition score changes, blood metabolite profiles, wool growth, and progeny wool follicle development. Thirty two pregnant Targhee ewes fed a grass hay diet were allotted randomly to four groups (n = 8) and supplemented with either SBM; 2/3 SBM:1/3 BM; 1/3 SBM:2/3 BM; or BM. Soybean meal, BM, or their combinations provided 22 g of dietary CP daily. Dietary treatments had no influence on ewe BW (P = .40) or body condition score (P = .77) changes, and ewes gained 7.6 kg of BW during the 84-d experiment. Protein source did not influence (P > .10) serum protein, urea N, creatinine, glucose, or nonesterified fatty acid concentrations. Lamb wool follicle density per square millimeter and secondary:primary follicle ratios were 22.4 and 10.8, respectively, and were not different (P > .10) among dietary treatments. Compared with SBM, no advantages were detected for BM supplementation of grass hay diets in these studies. PMID- 8478277 TI - Modeling gas production kinetics of grass silages incubated with buffered ruminal fluid. AB - Time course measurements of in vitro gas production of feedstuffs incubated with buffered ruminal fluid give information about the rate at which the feed is fermented. To compare gas production kinetics from different feeds, a mathematical model was needed to describe the data. We investigated several existing models (exponential, logistic, Gompertz, Richards, Schnute), fitting them to 50 gas production curves obtained with grass silages. None of them gave a satisfactory description of the data. A new model was developed (modified Gompertz model; mGom) that basically divided gas production into two fractions, one arising from rapidly fermentable feed components and the other from slowly fermentable feed components. Residual mean squares (RMS) for the mGom model were lower (P < .05; n = 50) than the RMS for the other models. A good statistical comparison of kinetic gas production data is made possible with the mGom model. PMID- 8478278 TI - Effect of protein source and grain type on finishing calf performance and ruminal metabolism. AB - A finishing trial and a metabolism trial were conducted to evaluate sources of supplemental protein in dry-rolled corn (DRC) and dry-rolled grain sorghum (DRGS) diets fed to large-framed calves and to determine effects of grain and protein source on ruminal metabolism. In Exp. 1, 144 Charolais crossbred steer and heifer calves (BW = 269 +/- 3 kg) were used in a randomized complete block design and fed (199 d) DRC or DRGS diets supplemented with urea or urea plus a 60:40 combination (CP basis) of blood meal (BM) and feather meal (FTH). Calves supplemented with urea-BM/FTH were more efficient (P < .05) during the first 41 d of the trial than were calves supplemented with urea alone. After 41 d, daily gain and feed efficiency were not affected (P > .2) by source of protein. The NRC metabolizable protein (MP) requirements accurately predicted response to urea BM/FTH. In Exp. 2, five ruminally cannulated steers (BW = 721 +/- 20 kg) were used in a 5 x 5 Latin square design and fed (on an ad libitum basis) diets similar to those used in Exp. 1. An additional treatment of DRC supplemented with soybean meal (SBM) was included. Rate (P < .01) and extent of 12-h (P = .14) and 18-h (P < .05) in situ N disappearance of SBM, BM, FTH, DRC, DRGS, and corn silage were greater when diets were supplemented with urea-BM/FTH or SBM. Estimates of escape N (percentage of total N) were 52.3, 93.3, 91.7, 65.7, 63.6, and 23.2% for SBM, BM, FTH, DRC, DRGS, and corn silage, respectively. Finishing calves supplemented with urea were deficient in MP during the early finishing period (0 to 41 d) but were adequate in MP from d 42 to slaughter. Supplementing urea-BM/FTH improved feed efficiency when MP was limiting but not when MP was adequate. PMID- 8478279 TI - Teaching principles of behavior and equipment design for handling livestock. AB - A course is described in which students are taught principles of livestock behavior and how an understanding of behavior can facilitate handling. Some of the principles that are covered in the course are livestock senses, flight zone, herd behavior during handling, and methods to reduce stress during handling. To teach problem solving and original thinking, the students design three different types of handling facilities. Design of restraint equipment and humane slaughter procedures are also covered. Both existing systems and ideas for future systems are discussed. Students are provided with information from both scientific studies and practical experience. PMID- 8478280 TI - Teaching standard agricultural practices that are known to be painful. AB - Animal science faculty teach, demonstrate, and ask students to perform procedures that are known to be painful. Potentially painful procedures include castration, branding, dehorning, ear notching, teeth clipping, beak trimming, comb and wattle removal, and tail docking. In each case, the degree of pain experienced by an animal is generally not known. Furthermore, the consequences of animals having to endure pain are also not fully understood. A survey was conducted of animal science faculty to identify current departmental policies and practices related to castration in beef and swine production classes. Departments vary in what they require of students. Departments should set a policy to address 1) which (and how) potentially painful procedures are taught and 2) how the faculty deal with students who refuse to participate in putatively painful procedures. The institutional animal care and use committee should approve potentially painful teaching procedures after instructor and department have concluded that teaching such procedures is essential to a complete educational experience. PMID- 8478281 TI - Effect of dietary fat and cholesterol level on tissue cholesterol concentrations of growing pigs selected for high or low serum cholesterol. AB - Thirty-six female pigs selected for three generations for high or low serum cholesterol were chosen to evaluate the effects of a high-fat, high-cholesterol diet and a low-fat, low-cholesterol diet provided on an ad libitum basis for 92 d beginning at 12 wk of age on the cholesterol content and percentage of fat in muscle and organ tissues. The pigs were four-way crosses (Chester White x Landrace x Large White x Yorkshire). Samples of cerebrum, heart, ileum, kidney, liver, longissimus muscle, semitendinosus muscle, and subcutaneous fat were collected from each animal for determination of cholesterol concentration. The liver was the only tissue that had a significant difference in cholesterol content and in fat percentage between the genetic groups (high serum cholesterol and low serum cholesterol) and between the two diets (high-fat, high-cholesterol diet and low-fat, low-cholesterol diet). There were no interactions between diet and genetic background on cholesterol accretion or on the percentage of fat in the tissues. PMID- 8478282 TI - Testis function and feedlot performance of bulls actively immunized against gonadotropin-releasing hormone: effect of implants containing progesterone and estradiol benzoate. AB - The effect of implants containing anabolic steroid (Synovex) on testis function, feedlot performance, and carcass traits was evaluated in bulls, steers, and bulls actively immunized against gonadotropin-releasing hormone (GnRH). Ninety-one Hereford or Hereford x Red Angus bull calves were randomly assigned to a 3 x 2 factorial experiment. The treatments were: 1) unimmunized control (n = 30), 2) actively immunized against GnRH (n = 31), or 3) castrate (n = 30). The classes were 1) unimplanted (n = 45) or 2) implanted (n = 46) with Synovex. Animals in treatment Groups 2 and 3 were either immunized with a GnRH-keyhole limpet hemocyanin (KLH) conjugate or castrated at 3.6 +/- .1 mo of age. Animals assigned to Class 2 received Synovex-C at the time of initial treatment and Synovex-S at weaning and feedlot entry. Animals in treatment Group 2 received a booster immunization at feedlot entry. Anti-GnRH titer was evident at weaning and remained elevated to slaughter in all (31 of 31) immunized animals. Anti-GnRH titer was not evident in steers or unimmunized bulls. Immunization and (or) Synovex decreased (P < .05) serum concentrations of testosterone (T) and scrotal circumference (SC) at weaning. Similarly, SC, testis weight, and tissue concentrations of spermatozoa at slaughter were significantly reduced by immunization, Synovex, or the immunization/Synovex combination. Immunization, but not Synovex, reduced (P < .05) serum levels of T at slaughter. The masculinity of immunized bulls was less (P < .05) than that of control bulls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478283 TI - Estimation of the water requirement for beef production in the United States. AB - A static model of developed water use for U.S. cattle production was constructed on a spreadsheet. Water use included that consumed directly by various classes of animals, water applied for irrigation of crops that are consumed by the cattle, water applied to irrigated pasture, and water used to process animals at marketing. Government statistics were consulted for numbers of cattle and crop production. The most recent statistics available for numbers of cattle and crops in individual states were used. On January 1, 1992, a total of 33.8 million beef cows and 5.7 million replacement heifers were in U.S. breeding herds, 12 million animals were on feed, and approximately 28 million animals were fed annually. Thus, the U.S. beef cattle herd produced 6.9 billion kg of boneless beef. Beef cattle directly consumed 760 billion L of water per year. Feedlot cattle were fed various grain and roughage sources corresponding to the regions in which they were fed. Feeds produced in a state were preferentially used by cattle in that state with that state's efficiency; any additional feedstuffs required used water at the national efficiency. Irrigation of crop feedstuffs for beef cattle required 12,991 billion L of water. Irrigated pasture for beef cattle production required an additional 11,243 billion L of water. Carcass processing required 79 billion L of water. The model estimates 3,682 L of developed water per kilogram of boneless meat for beef cattle production in the United States. The model was most sensitive to the dressing percentage and percentage of boneless yield in carcasses of feedlot cattle (62 and 66.7, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478284 TI - Dose-dependent effects of exogenous porcine somatotropin on the yield, distribution, and proximate composition of carcass tissues in growing pigs. AB - Dose-dependent effects of porcine somatotropin (pST) on mass, distribution, and proximate composition of carcass tissues were investigated in 46 growing pigs. Barrows, weighing 30 +/- 1 kg, were assigned to five treatment groups to receive 0, 50, 100, 150, or 200 micrograms of recombinant pST/kg BW per day until pigs individually reached the 90-kg slaughter weight. Left carcass sides were fabricated into whole-sale cuts that were separated into muscle, adipose tissue, bone, and skin. Despite the reduction in dressing percentage, total muscle mass of the side was significantly increased by 3.9 to 5.7 kg (28 to 36%) by the lowest and highest doses of pST, respectively, whereas adipose tissue mass was decreased by 4.4 to 8.6 kg (38 to 74%). Bone mass was increased by 8 to 27% (P < .05), and skin mass was increased by 16 to 38% (P < .01) across the dose range. Distribution of carcass weight among the wholesale cuts was altered by pST toward lower proportions in the belly, jowl, and fat trimmings and greater proportions in the four lean cuts. Porcine somatotropin substantially reduced lipid concentration in all muscle groups in a dose-dependent manner, resulting in increased protein and moisture concentrations (P < .05). Adipose tissue lipid concentrations were reduced to an even greater extent at each dose. The progressive increase in muscle mass observed with pST doses > 50 micrograms/kg BW was less than the associated decrease in adipose tissue mass, indicating that a dose range of 50 to 100 micrograms/kg BW per day may be optimum for improving carcass value. PMID- 8478285 TI - Sequential transformation for multiple traits for estimation of (co)variance components with a derivative-free algorithm for restricted maximum likelihood. AB - Transformation of multiple-trait records that undergo sequential selection can be used with derivative-free algorithms to maximize the restricted likelihood in estimation of covariance matrices as with derivative methods. Data transformation with appropriate parts of the Choleski decomposition of the current estimate of the residual covariance matrix results in mixed-model equations that are easily modified from round to round for calculation of the logarithm of the likelihood. The residual sum of squares is the same for transformed and untransformed analyses. Most importantly, the logarithm of the determinant of the untransformed coefficient matrix is an easily determined function of the Choleski decomposition of the residual covariance matrix and the determinant of the transformed coefficient matrix. Thus, the logarithm of the likelihood for any combination of covariance matrices can be determined from the transformed equations. Advantages of transformation are 1) the multiple-trait mixed-model equations are easy to set up, 2) the least squares part of the equations does not change from round to round, 3) right-hand sides change from round to round by constant multipliers, and 4) less memory is required. An example showed only a slight advantage of the transformation compared with no transformation in terms of solution time for each round (1 to 5%). PMID- 8478286 TI - Estimates of variances due to direct and maternal effects for growth traits of Romanov sheep. AB - Records of growth traits of 2,086 Romanov lambs were used to estimate variance components for an animal model and genetic correlations between growth traits. Traits analyzed were birth weight (BWT), weaning weight (WW), 90-d weight (W90), and daily gain for the periods birth to weaning (DG1) and weaning to 90 d (DG2). Weaning was at approximately 40 d. Variance components were estimated using restricted maximum likelihood with an animal model including fixed effects for year x season, sex, rearing type, and litter size and random effects for the direct genetic effect of the animal (with relative variance h2), the maternal genetic effect (with relative variance m2), the permanent environmental effect (with relative variance c2), and random residual effect. Genetic correlations were estimated for a model with the same fixed effects and only additive genetic effects. Estimates of the variances of random effects, h2, m2, and c2, respectively, as a proportion of phenotypic variance were .04, .22, .10 (BWT); .34, .25, .0 (WW); .09, .01, .07 (W90); .26, .17, .02 (DG1); and .15, .01, .03 (DG2). Estimates of genetic correlations were .12 (BWT with WW); .24 (BWT with W90); .48 (WW with W90); .69 (DG1 with DG2); -.01 (BWT with DG1); .05 (BWT with DG2); .59 (WW with DG1); .47 (WW with DG2); .67 (W90 with DG1); and .98 (W90 with DG2). Results suggest that selection should be effective for WW, DG1, and DG2 but less effective for BWT and W90. An important maternal effect was observed for BWT, WW, and DG1. The estimates of genetic correlations showed no genetic antagonisms among the traits. PMID- 8478287 TI - Animal model estimation of genetic parameters and response to selection for litter size and weight, growth, and backfat in closed seedstock populations of large white and Landrace swine. AB - Records from 2,495 litters and 14,605 Landrace and Large White pigs from two farms, but established from the same base population and run as replicated selection lines, were analyzed. Selection within herd was on estimated breeding values weighted by economic values. Animal models and REML procedures were used to estimate genetic, phenotypic, and environmental parameters for the number of pigs born alive (NBA), litter weight at 21 d (LW), average daily gain form approximately 30 to 104 kg (ADG), and backfat thickness adjusted to 104 kg (BF). Random animal genetic effects (o), permanent (NBA and LW) or litter (ADG and BF) environmental effects, maternal genetic effects (m), and the covariance between o and m were sequentially added to the model. Estimates of total heritability calculated from all data (ht2 = sigma o2 + 1/2 sigma m2 + 3/2 sigma om) ranged from .01 to .14 for NBA, from .18 to .22 for LW, from .23 to .34 for ADG, and from .40 to .50 for BF. Maternal genetic variance was from 2.4 to 3.8% of phenotypic variance in NBA, from 1.2 to 3.6% in LW, from .5 to 1.5% in ADG, and from 1.9 to 3.4% in BF. The correlation between o and m was -.07 for NBA, -.25 for LW, -.34 for ADG, and -.26 for BF. Permanent environmental effects explained from 16 to 17% of total phenotypic variation for NBA and from 1.6 to 5.3% for LW. Approximately 7% of the variation in ADG and 5% in BF was due to litter environmental effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478288 TI - Comparison of Texel- and Suffolk-sired crossbred lambs for survival, growth, and compositional traits. AB - Texel sheep were imported from Finland and Denmark for evaluation as a terminal sire population relative to the Suffolk breed. The objective was to estimate effects of sire breed on fitness, growth, and compositional traits of crossbred progeny that were serially slaughtered at 63, 105, 147, and 189 d of age. A total of 325 lambs, sired by 19 Texel and 20 Suffolk rams, were born to mature, half Finnsheep ewes during a 2-yr period. Carcass traits were recorded on 183 lambs. Texel-sired lambs had greater survival to weaning (P = .06) and similar birth and weaning weights compared with Suffolk progeny. Lambs by Texel sires grew 11% less rapidly from 63 to 189 d of age. Estimated accretion rates of carcass fat at 189 d of age were 96.1 and 78.5 g/d for Suffolk and Texel progeny, respectively. Corresponding values for carcass protein were 17.4 and 16.0 g/d. At fixed ages, area of the longissimus muscle did not differ between sire breeds. Texel progeny weighed less at 189 d of age, producing lighter, leaner carcasses of shorter length (P < .05). Compositional differences were not detected when sire breeds were compared at 25 kg of carcass weight. However, Texel progeny had significantly greater depth of fat at the 12th rib and weight of kidney-pelvic fat. Data indicated that Texel-sired lambs deposited proportionally more subcutaneous and less intermuscular fat than did lambs by Suffolk sires. Due to the apparent advantage in lamb survival and the observation that Texel progeny produce lean carcasses relative to the intermediate growth rate and mature size characteristic of the breed, it is concluded that Texel sheep can be used effectively as a terminal sire breed. PMID- 8478289 TI - Diallel cross of three Moroccan breeds of sheep: I. Lamb growth and carcass traits. AB - A diallel cross involving three Moroccan breeds of sheep (D'man, Beni Guil, and Sardi) was conducted for two successive years at the Gharb Experiment Station in Morocco. Significant effects associated with breed of sire and breed of dam for live and carcass weights are consistent with differences in mature body size of the three breeds involved. Carcasses of lambs by Sardi sires or out of Sardi dams were the heaviest and those by D'man sires or out of D'man dams were the lightest. Lambs by D'man sires reached the prescribed stage of maturity for slaughter at a younger age than did lambs of Beni Guil sires, and lambs out of Beni Guil dams were younger at slaughter than lambs out of Sardi dams. Because of its genetic potential for high growth rate and carcass weight, the Sardi breed could be used in breeding programs to enhance meat production from sheep in Morocco. With the large and desirable maternal effects expressed by the Beni Guil breed on growth traits and carcass weight per 100 d of age, it could also be used in Morocco as a breed of dam. PMID- 8478290 TI - Diallel cross of three Moroccan breeds of sheep: II. Reproductive performance and productivity of purebred ewes. AB - A diallel cross involving three Moroccan breeds of sheep (Sardi, Beni Guil, and D'man) was analyzed by least squares procedures. A total of 456 ewes were mated to 22 rams and this resulted in 528 lambs born from 412 ewes. D'man ewes had by far the highest general performance as measured by total weight of lamb weaned, even though the average live weight per lamb was the lowest for the three breeds; this resulted from the higher number of lambs weaned per ewe for the D'man. The least squares means for litter size at birth per ewe lambing were 2.04, 1.01, and 1.11 for D'man, Beni Guil, and Sardi ewes, respectively. The comparable figures for litter size at weaning were 1.55, .90, and .99, respectively, and the least squares means for total weight of lamb weaned were 20.7, 16.9, and 18.2 kg for D'man, Beni Guil, and Sardi ewes, respectively. The comparable figures for total weight of lamb weaned per 100 kg of ewe weight were 71.1, 44.3, and 41.1 kg/100 kg for D'man, Beni Guil, and Sardi ewes. Conversely, D'man rams had the poorest breeding performances of the rams of the three breeds, and Beni Guil rams had the lowest litter mortality. The breed of ram had only small and nonsignificant effects on all measures of fertility and ewe productivity. The least squares means for number born/ewe lambing were 1.36, 1.35, and 1.44, respectively, for D'man, Beni Guil, and Sardi rams; the comparable least squares means for number weaned per ewe lambing were 1.10, 1.18, and 1.16, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478291 TI - Shipping stress and social status effects on pig performance, plasma cortisol, natural killer cell activity, and leukocyte numbers. AB - Crossbred pigs were used to evaluate the effects of shipping stress on natural killer (NK) cell activity, leukocyte numbers, plasma cortisol, and BW changes. In the first study, pigs were bled at a commercial farm and, after shipping, resident and shipped pigs were bled again. Plasma cortisol concentrations were not different (P > .10) because of large variation in cortisol concentrations. Furthermore, NK cytotoxicity was nondetectable among all pigs. A second study showed that plasma cortisol concentration rose by approximately 2.6 ng/mL (P = .018) for each minute after pigs were aroused. In the third, more controlled study, pigs were housed in pens of three pigs each. Video recordings were made during the first 24 h pigs were grouped to identify socially dominant, intermediate, and submissive pigs. At time zero (before shipping), resident pigs and those to be shipped had similar plasma cortisol concentrations. However, after the 4-h shipping experience, shipped pigs had elevated (P < .05) plasma cortisol compared with resident control pigs. Shipped pigs lost 5.1% of their BW (P < .05) compared with resident pigs, which gained .02% of their BW. Body weight change during shipping and plasma cortisol were negatively correlated (r = -.34, P = .04), indicating pigs that had greater adrenal response to shipping also lost more weight during shipping. Shipping reduced (P < .05) NK cytotoxicity among pigs of intermediate and submissive social status compared with shipped, dominant pigs. At the end of shipping or control treatments, the correlation between NK cytotoxicity and plasma cortisol was positive (r = .35, P = .036), indicating that pigs with greater cortisol response had greater NK cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478292 TI - Acute effects of administration of porcine growth hormone on circulating levels of hormones and metabolites in 20-, 40-, and 60-kilogram gilts. AB - Three groups of eight gilts weighing 20, 40, or 60 kg were fitted with indwelling venous catheters to determine daily integrated circulating levels (DICL, serum concentration above baseline x time) of insulin, growth hormone (GH), glucagon, glucose, urea, and nonesterified fatty acids (NEFA) in response to acute challenge with porcine pituitary GH (pGH). Pigs were fed a common diet containing 18% CP and 3.5 Mcal of DE/kg between 0800 and 1200 (85% of ad libitum). Blood and urine were collected at 2- or 4-h intervals for 4 d. On d 2, 3, and 4, four pigs in each group were injected i.m. at 0800 with pGH (.1 mg/kg) and four pigs (controls) were injected with buffer. In control pigs DICL of GH was 20.4, 14.1, and 10.2 ng pGH.h.mL-1 in 20-, 40-, and 60-kg pigs, respectively. The DICL of GH in pGH-treated pigs was 4.2-, 7.0-, and 10.7-fold greater in 20-, 40-, and 60-kg pigs, respectively, than in controls. The DICL of insulin in control pigs was 7.9, 9.7, and 9.4 ng.h.mL-1 and was increased (P < .001) in pGH-treated pigs by 118, 213, and 276% in 20-, 40-, and 60-kg pigs, respectively. Although serum levels of glucose were increased (P < .001) by pGH treatment, the acute elevation observed in 60-kg pigs was more consistent relative to 20- and 40-kg pigs. In contrast, the acute reduction in blood urea upon pGH injection was more apparent in 20-kg gilts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478293 TI - Muscle histochemical and biochemical properties in relation to meat quality during selection for increased lean tissue growth rate in pigs. AB - The relationship between the histochemical and biochemical properties of muscle and the quality of meat during selection to improving the lean tissue growth rate was studied. Pigs (n = 82) from Generations 2 and 4 were randomly sampled in a selection experiment in which the genotype x protein interaction was studied. Comparisons were made of longissimus muscle (LM) and quadriceps femoris (QF) from Generations 2 and 4, and biceps femoris (BF) in the fourth generation from pigs fed a low- or high-protein diet. A higher total growth rate, lean tissue growth rate, and lean percentage were found in pigs fed the high-protein diet than in pigs fed the low-protein diet. Pigs fed the high-protein diet had a higher glycolytic capacity in all muscles than pigs fed the low-protein diet. When the meat quality traits were compared, pigs fed the high-protein diet had a lower intramuscular fat content, higher shear force value, higher protein extractability, lower light reflectance, and somewhat higher water-holding capacity. With selection, pigs became fatter on both diets. In Generation 4, glycolytic and oxidative capacity was somewhat higher in muscle tissue than in Generation 2. Muscle metabolic profile and meat quality traits differed among muscles (LM, BF, QF) but no pronounced differences were found between generations. No marked changes were observed in Type I, IIA, or IIB fibers, either between diets or between generations. The Type IIC fibers could only be identified in Generation 4. PMID- 8478294 TI - Effect of heating rate on palatability and associated properties of pre- and postrigor muscle. AB - Precooked, uncured meat is not widely available to consumers, partially because of associated palatability problems and lack of published information on heat uptake under different industrial conditions. The objectives of this study were to determine the tenderness, extent of lipid oxidation, and total cooking losses in pre- and posterior beef and pork roasts heated at different rates. The muscles were cooked in stainless-steel, perforated heating chambers at oven temperatures of 150, 200, or 250 degrees C and the temperature rise during and after heating was monitored with a digital temperature recorder. Samples were vacuum-packaged, frozen at -20 degrees C for 45 d, thawed at 4 degrees C for 24 h, and reheated in 60 degrees C water for 1 h. Cooking losses, Warner-Bratzler shear force values, thiobarbituric acid values, and pH were determined. The results provide heating curves for pre- and postrigor beef and pork roasts at three oven temperatures. Prerigor samples of both species were less tender than postrigor samples (P < .05). Cooking losses were generally low in prerigor samples of both species compared with postrigor samples (P < .05). All beef samples had relatively low thiobarbituric acid (TBA) values before and after storage, whereas pork samples had relatively high TBA values before and after storage. Results indicate that prerigor cooked roasts shrink less, are equivalent or better in oxidative stability, and are less tender than postrigor cooked roasts under the conditions of this experiment. PMID- 8478295 TI - Zinc-silicon interactions influencing sperm chromatin integrity and testicular cell development in the rat as measured by flow cytometry. AB - Flow-cytometric procedures were used to determine effects of dietary Zn and Si variations on rat testicular cell development, including integrity of caudal epididymal sperm chromatin structure defined as the susceptibility of DNA to denaturation in situ. Concentrations of 4 (deficient), 12 (adequate), and 500 (excessive) mg of Zn/kg of diet were used with Si concentrations of 0 (low), 540 (medium), and 2,700 (high) mg/kg of diet in a 3 x 3 factorial arrangement. Three week-old Sprague-Dawley male rats were fed the experimental diets for 8 wk. Rats fed the Zn-deficient/Si-low diet demonstrated significant deviations in the ratio of testicular cell types present, including a reduction of S phase and total haploid cells. Furthermore, approximately 50% of epididymal sperm had a significant decrease in resistance to DNA denaturation in situ. In the Zn deficient/Si-medium treatment, the effects of Si on animal and testicular growth, distribution of testicular cell types, and sperm chromatin structure integrity were quite similar to the effects of the Zn-adequate diets. A toxic effect of Zn on sperm chromatin structure integrity observed in the Zn-excess/Si-medium treatment seemed to be counteracted by Si in the Zn-excess/Si-high treatment. Silicon at medium and high levels seems to affect Zn metabolism through potentiation and antagonistic reactions, respectively. Zinc deficiency likely disrupts the normal sperm chromatin quaternary structure in which Zn plays a role by providing stability and resistance to DNA denaturation in situ. PMID- 8478296 TI - Microbially detoxified vomitoxin-contaminated corn for young pigs. AB - A performance trial was conducted to evaluate the effect of microbially detoxified moldy corn in a corn-soybean meal-based starter diet for young pigs. Moldy corn containing 450 ppm of vomitoxin replaced clean corn in a control diet to give a diet containing 5 ppm of vomitoxin. The same amount of moldy corn was microbially detoxified by incubation with the contents of the large intestine of chickens (CLIC) and then incorporated into the control diet to give a "detoxified" vomitoxin diet, which contained 2.1 ppm of vomitoxin. A paired diet was formulated by incorporating the untreated moldy corn into the control diet to give a diet containing the same level of vomitoxin as the "detoxified" vomitoxin diet. Clean corn was also treated with CLIC and replaced corn in the control diet to give a biologically treated control diet. Each diet was fed to six pigs (three gilts and three boars) for 5 d and then all pigs were changed to the control diet for a further 5-d feeding period. During the first 5-d feeding period, no differences were observed in pigs fed either the control diet or the biologically treated control diet. A diet containing 5 ppm of vomitoxin decreased the pigs' daily feed consumption, weight gain, and feed efficiency by 25, 57, and 45%, respectively, compared with the control diet (P < or = .05). Daily feed intake, weight gain, and feed efficiency in pigs fed the "detoxified" vomitoxin diet were 19, 54, and 37% greater, respectively, than for pigs fed the vomitoxin diet (P < or = .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478297 TI - Ovulatory and endocrine responses after active immunization of gilts against a synthetic fragment of bovine inhibin. AB - The objective of this study was to determine whether neutralizing endogenous inhibin would affect ovulation rate and serum concentrations of FSH, LH, estradiol-17 beta, and progesterone in gilts. At wk 0, during their second postpubertal estrous cycle, gilts (195 +/- 2.4 d of age) were given a primary immunization against the 1-26 gly-tyr NH-terminal amino acid sequence of bovine inhibin-alpha conjugated to human alpha globulin (INH; n = 10) or against human alpha globulin alone (control; n = 10). The primary immunization mixed with Freund's complete adjuvant contained .915 mg of the inhibin peptide. Booster immunizations in Freund's incomplete adjuvant contained .3 and .183 mg of the inhibin peptide and were given at wk 8 and 12, respectively. Free, unconjugated inhibin was given to INH gilts at 16 wk. Blood samples for determination of hormones were collected every 4 h beginning on d 15 of the first estrous cycle beyond wk 16 (first cycle) and continuing until d 5 of the second estrous cycle following wk 16 (second cycle). Ovulation rate was estimated by laparoscopy during the second cycle. Antibody titers were estimated by determining the percentage of [125I]-INH bound by serum diluted 1:4,000. The antibody titers were 17 +/- 2, 22 +/- 3, and 9 +/- 1% at wk 9, 17, and 23 for INH gilts, respectively, and 0% at all times for control gilts. Duration of three consecutive estrous cycles terminating with the first experimental cycle did not differ between treatments (INH, 20.7 +/- .3 vs control, 20.4 +/- .3 d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478298 TI - Influence of stage of lactation, exogenous luteinizing hormone-releasing hormone, and suckling on estrus, positive feedback of luteinizing hormone, and ovulation in sows treated with estrogen. AB - The overall objective of this study was to investigate the LH response and occurrence of estrus and ovulation in sows treated with estradiol benzoate (EB) at mid- (d 14) or late (d 28) lactation. Experiment 1 tested the hypothesis that hourly pulses of LHRH given to sows treated with EB would cause a greater proportion to exhibit LH surges. Sows (n = 32) at mid- or late lactation were given (i.m.) corn oil (CO) or EB (10 micrograms/kg BW) at 0 h and no pulses or hourly pulses (100 ng/pulse) of the LHRH agonist des-Gly10,[D-ALA6]-LHRH ethylamide (LHRH-A) from 54 to 96 h, the anticipated period of positive feedback of LH. Blood samples for determination of estradiol-17 beta (E2) and LH were collected every 6 h from -12 to 120 h from sows treated with EB. Estrus was checked daily with a mature boar, and ovulation was assessed by measuring progesterone in blood 1 wk after estrus induced by EB or 2 wk after weaning at 34 +/- 1.4 d postpartum. Lactational estrus occurred in 0 of 16 and 15 of 16 sows given CO and EB, respectively; however, no sow ovulated in response to EB. Concentrations of LH were lower (P < .01) during mid- than during late lactation, and LHRH-A pulses had no effect on secretion of LH and E2. The LH concentrations during the pretreatment (-12 to 0 h), negative feedback (6 to 54 h), and positive feedback (60 to 96 h) periods at mid-lactation (.32 +/- .03, .22 +/- .01, and .54 +/- .08 ng/mL, respectively) differed (P < .01) from values at late lactation (.80 +/- .06, .49 +/- .02, and 1.47 +/- .17, respectively). Preovulatory-like surges of LH occurred in one of eight (peak 2.1 ng/mL) and seven of eight (peak 2.9 +/- 1 ng/mL) sows given EB at mid- and late lactation, respectively. Experiment 2 tested the hypothesis that the hypothalamus and pituitary of sows weaned 96 h before they were given EB would show a greater responsiveness than those weaned and given EB simultaneously. Sows (n = 16) at mid- or late lactation were treated with EB (10 micrograms/kg BW; i.m.), and one-half of the sows were suckled until the moment of EB treatment, whereas the other half had their litters weaned 96 h before treatment with EB.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478299 TI - Prolonged postpartum anovulation in mastectomized cows requires tactile stimulation by the calf. AB - Association of the calf with its dam prolongs the postpartum interval to first ovulation in intact and mastectomized cows indicating that tactile stimulus of the teat and (or) udder is not necessary. Therefore, we conducted the following experiment to determine whether individual calves allowed restricted contact with their mastectomized dam would delay the onset of first postpartum ovulation. Mastectomized cows (n = 21) were allotted randomly and equally to three groups in which cows were 1) allowed unrestricted access to their calves, with unlimited tactile, olfactory, visual, and auditory stimuli (calf present); 2) removed permanently from their calves 24 h after parturition and provided no further association with their calves (calf removed); and 3) remained with their calves for 24 h and then the cow-calf pair was restricted to a pen where tactile contact of the calf was limited to the head and neck region of its dam (calf restricted). Seven udder-intact cows (control) remained with their calves and were allowed to nurse ad libitum. Postpartum intervals to ovulation and first estrus for the calf restricted cows and calf-removed cows were similar but shorter (P < .05) than those for the calf-present and udder-intact groups. We conclude that restricting tactile stimuli of the calf to the head and neck area of its dam failed to prolong postpartum anovulation in the mastectomized dam and that a cow-calf nursing orientation with tactile stimuli to the inguinal area, but not limited to the teat and(or) udder, was sufficient to prolong anovulation. PMID- 8478300 TI - Clinical efficacy of dirithromycin versus miocamycin in tonsillopharyngitis. AB - A single-blind, randomized, parallel-group study was conducted to compare the efficacy and safety of dirithromycin with miocamycin in the treatment of streptococcal pharyngitis/tonsillitis caused by Group A streptococci. The study population consisted of 60 patients: 30 were randomized to receive 500 mg dirithromycin od and 30 to receive 600 mg miocamycin bd. All 30 dirithromycin treated patients were eligible for efficacy analysis. A favourable clinical response was observed in 100% of these patients at the post-therapy visit. In the miocamycin-treated group, 28 of 30 (93.3%) patients were eligible for efficacy analysis; a favourable clinical response was observed in 100%. Bacteriological cure of evaluable dirithromycin- and miocamycin-treated patients was 96.7% and 92.9%, respectively. No statistically significant post-therapy differences in clinical or bacteriological response rates were noted between the two groups. Adverse event analysis showed no significant differences between treatment groups. There were no serious adverse events during the study. Two miocamycin treated patients were prematurely withdrawn from the study due to adverse events (diarrhoea). Analysis of clinical laboratory data revealed no statistically significant differences between the treatment groups that were considered to be drug related. The results of this study suggest that dirithromycin has comparable safety and efficacy to miocamycin in the treatment of streptococcal pharyngitis/tonsillitis infections caused by Group A streptococci. PMID- 8478301 TI - Comparison of macrolide antibiotics. AB - Macrolides have been in use since the early 1950s. In recent years new macrolides have been developed to try to overcome the problems associated with erythromycin. In general they have fairly similar in-vitro activity, although azithromycin has superior activity against Haemophilus influenzae and some Gram-negative organisms. Clarithromycin shows superior in-vitro activity against Legionella spp. and against the type strain of Chlamydia pneumoniae. The pharmacology of macrolides produces many interpretive problems, and macrolides show marked variation in their pharmacokinetic parameters, tissue affinity and intracellular penetration. Newer macrolides such as clarithromycin, roxithromycin, dirithromycin and azithromycin only need to be taken once or twice a day, which is likely to improve patient compliance. Few objective side-effect studies have been performed with the newer macrolides. Clinical efficacy studies are essential to elucidate the significance of the complex pharmacology of macrolides. PMID- 8478302 TI - The problems of treating atypical pneumonia. AB - Atypical pneumonia has been recognized for at least four decades as a clinical syndrome characterized by a less severe clinical course than typical bacterial pneumonia. It is caused by a variety of different organisms including Mycoplasma pneumoniae, chlamydiae, rickettsiae, viruses and Legionella pneumophila. Of the chlamydiae, TWAR-strain (Chlamydia pneumonia) is now considered the most important pathogen. Its prevalence in community-acquired pneumonia varies considerably depending on the cyclical nature of the disease, but also on the diagnostic methods applied. The first line therapy in community-acquired pneumonia is usually empirical administration of a penicillin or cephalosporin to cover the bacterial pathogens which usually cause 'typical' pneumonia, most importantly Streptococcus pneumoniae. If, however, atypical pneumonia is diagnosed by bacteriological or serological testing, or is suspected clinically or on the basis of treatment failure, the treatment of choice would be erythromycin 2-4 g or tetracyclines (doxycycline 200 mg) daily for M. pneumoniae pneumonia and C. pneumoniae (TWAR-strain) infection. For coxiella pneumonia tetracycline is preferred. Psittacosis (ornithosis) has a high mortality and must be treated with tetracyclines immediately. Legionella pneumonia is preferably treated with erythromycin 2-4 g for at least three weeks; as an alternative, tetracyclines or quinolones may be given. Quinolones are less effective in mycoplasma and chlamydial infection. The new macrolide antibiotics are promising agents in pneumonia due to M. pneumoniae, L. pneumophila and C. pneumoniae. Compared to erythromycin they have improved pharmacological properties. They have long half-lives allowing once-daily dosing and achieve high tissue and intracellular concentrations. PMID- 8478303 TI - Clinical efficacy of dirithromycin in pneumonia. AB - In a double-blind, double-dummy, multicentre study the efficacy and safety of dirithromycin 500 mg/day given orally once daily for 10-14 days were compared with those of erythromycin 1000 mg/day given orally four times daily for 10-14 days in patients with bacterial pneumonia. At 3-5 days post-therapy, 90 dirithromycin- and 83 erythromycin-treated patients were evaluable; the main reason for non-evaluability was failure to isolate the causative organism. Symptomatic responses were favourable in 94.5% of dirithromycin- and 100% of erythromycin-treated patients at post-therapy. At late post-therapy (2-3 weeks after completion of treatment), symptomatic responses were favourable in 98.7% of dirithromycin- and 94.8% of erythromycin-treated patients. At post-therapy, 63.3% of dirithromycin- and 50.6% of erythromycin-treated patients were unable to be evaluated bacteriologically, mainly due to Mycoplasma pneumoniae or Legionella pneumophila being assessed serologically. In the remaining evaluable patients treated with dirithromycin and erythromycin, bacteriological responses were favourable in 91.4% and 87.8%, respectively. At late post-therapy, favourable bacteriological responses occurred in 89.7% and 86.8%, respectively, of dirithromycin- and erythromycin-treated patients. Abdominal pain was the only treatment-emergent event to occur significantly more frequently in dirithromycin treated patients. PMID- 8478304 TI - Clinical efficacy of dirithromycin in acute exacerbations of chronic bronchitis. AB - The efficacy and safety of seven days treatment with oral dirithromycin 500 mg given once daily was compared with oral erythromycin 250 mg qid in patients with acute bacterial exacerbations of chronic bronchitis. A total of 393 patients received dirithromycin and 409 erythromycin. Of 101 dirithromycin-treated patients analysed for efficacy, 87 (86%) had favourable clinical responses compared with 72/81 (89%) of those treated with erythromycin. Proven or presumed pathogen elimination was noted in 85/101 (84%) dirithromycin-treated patients and 66/81 (82%) erythromycin treated patients. Late post-therapy responses were also similar between treatment groups. Favourable clinical responses were noted in 89% of patients treated with dirithromycin and 91% of those receiving erythromycin. A favourable bacteriological response was noted in 87.5% and 89.6% of the dirithromycin- and erythromycin-treated groups, respectively. Adverse events were also similar between treatment groups. Gastrointestinal events were the most common events in both groups of patients; erythromycin was associated with a significantly higher incidence of diarrhoea (P = 0.003). Dirithromycin was associated with a higher incidence of lung events (P = 0.043). It is concluded that dirithromycin given once a day is comparable in efficacy and safety to four times-daily erythromycin in the treatment of acute bacterial exacerbations of chronic bronchitis. PMID- 8478305 TI - A multicentre study comparing the safety and efficacy of dirithromycin with erythromycin in the treatment of bronchitis. AB - This European multicentre (110 centres), double-blind, randomized clinical trial compared the safety and efficacy of dirithromycin (500 mg orally once daily) and erythromycin (250 mg orally qds) in the treatment of either acute bacterial bronchitis or acute bacterial exacerbations of chronic bronchitis. From January 1989 to September 1990, 1222 patients (529 with acute bronchitis and 693 with acute exacerbations of chronic bronchitis) were included in the trial. Clinical and bacteriological evaluations were performed on 135 evaluable patients with acute bronchitis (72 in the dirithromycin group and 63 in the erythromycin group) and in 202 patients with acute exacerbations of chronic bronchitis (89 treated with dirithromycin and 113 treated with erythromycin). Evaluations were performed during treatment (days 3-5), post-therapy (three to five days after therapy completion), and late post-therapy (10-14 days following the end of therapy). In acute bronchitis, both drugs were effective with clinical success rates of 93.0% and 95.2% at post-therapy, and 96.9% and 100% at late post-therapy for dirithromycin and erythromycin, respectively. Pathogen eradication rates at post therapy were 83.3% for the dirithromycin group and 85.7% for the erythromycin group. In acute exacerbations of chronic bronchitis, the drugs were also effective with 89.9% and 92.1% cure or improvement at post-therapy and 98.7% and 95.0% at late post-therapy for dirithromycin and erythromycin, respectively. Pathogen eradication rates were 75.3% in both treatment groups. There were no statistically significant differences in clinical and bacteriological results between treatments in patients with acute bronchitis or acute exacerbations of chronic bronchitis. Of the 1222 patients included, no significant differences in the number of patients reporting adverse events were observed. There were nine early discontinuations due to adverse events in the dirithromycin group and 14 in the erythromycin group. Dirithromycin (500 mg once daily for seven days) was as effective and as safe as erythromycin (250 mg qid for seven days) in the treatment of acute bacterial bronchitis and acute bacterial exacerbations of chronic bronchitis. PMID- 8478306 TI - Clinical efficacy of dirithromycin versus miocamycin in the treatment of acute bronchitis or acute exacerbations of chronic bronchitis. AB - A multicentre trial was carried out to compare the efficacy and safety of dirithromycin with miocamycin in the treatment of patients with acute bronchitis or acute exacerbations of chronic bronchitis. The study was a single-blind, randomized, parallel-group study. Dirithromycin was administered orally at a dosage of 500 mg once daily and miocamycin was administered orally at a dosage of 600 mg twice daily; the duration of therapy was five to seven days for both drugs. The results, in 161 assessable patients (78 taking dirithromycin; 83 taking miocamycin), show that dirithromycin and miocamycin have comparable efficacy and safety in the treatment of bronchitis caused by susceptible bacterial pathogens. PMID- 8478307 TI - Dirithromycin in the treatment of skin and skin structure infections. AB - The efficacy and safety of dirithromycin were compared with those of erythromycin or miocamycin for the treatment of skin and/or skin structure infections in two double-blind, double-dummy, randomized, parallel group, multicentre studies conducted in North America and in Europe, and one single-blind, randomized, parallel group study conducted in Italy. The US and European study patients, in which bacterial infection was confirmed by culture, received either dirithromycin 500 mg once daily or erythromycin base 250 mg four times daily for seven days. Patients in the Italian trial were treated with either 500 mg dirithromycin once daily or with 600 mg miocamycin twice daily for seven days. A total of 156 of the 304 US patients treated with dirithromycin and 127 of the 274 patients treated with erythromycin qualified for efficacy analysis post-therapy. At the post therapy evaluation, 112 (71.8%) dirithromycin-treated patients were cured and 34 (21.8%) improved compared with 94 (74.0%) and 25 (19.7%) patients treated with erythromycin. The pathogen was eliminated or presumably eliminated in 136 (87.2%) and 110 (86.6%) dirithromycin- and erythromycin-treated patients, respectively. A total of 100 of the 193 dirithromycin-treated patients qualified for efficacy analysis, as did 99 of the 198 erythromycin-treated patients in the European study at post-therapy. Favourable clinical responses (cure or improvement) at the post-therapy visit were recorded in 96 (96.0%) dirithromycin- and 98 (99%) erythromycin-treated patients, and pathogens were eliminated or presumed to have been eliminated in 87 (87.0%) and 88 (88.9%) patients respectively, in the dirithromycin and erythromycin treatment groups. Efficacy analysis was performed in 56 of the 70 Italian patients treated with dirithromycin and in 62 of the 71 patients treated with miocamycin. At post-therapy evaluation, a favourable clinical response was observed in 98.2% of the dirithromycin-treated patients compared with 95.1% of miocamycin-treated patients, whereas a favourable bacteriological response was observed in 52 (92.9%) dirithromycin- and 52 (83.9%) miocamycin-treated patients respectively. In all studies no serious treatment related events were noted. Events most frequently reported were gastrointestinal in nature. Overall in the three studies, no statistically significant differences were observed between two treatment groups in the clinical and bacteriological outcomes. PMID- 8478308 TI - Pharmacokinetics and safety of dirithromycin in the elderly. AB - Pharmacokinetic and safety studies were undertaken in elderly (age > or = 65 years) and non-elderly (age 18-50 years) subjects receiving the normal recommended dose of 500 mg/day dirithromycin for ten days. There was a considerable variation in the maximum plasma concentration and time when this was achieved in each of the subject groups. There was also a trend for values for the area under the plasma concentration versus time curve to increase with age, but neither of these pharmacokinetic parameters was significantly altered with age. The incidence and nature of adverse events were similar in elderly and non elderly subjects, and there was no electrocardiographic evidence that dirithromycin caused an increased incidence of cardiac disturbances. No changes in clinical laboratory values were thought to be due to dirithromycin. It is concluded that 500 mg/day dirithromycin may be used to treat elderly patients without the need for any dose adjustment. PMID- 8478309 TI - Safety profile of dirithromycin. AB - Dirithromycin is a recently developed oral antibiotic, and has been shown to be effective in the treatment of respiratory tract, skin and soft tissue infections. Dirithromycin is administered once daily which may contribute to patient compliance. In this paper we review the data from studies conducted in Europe, USA, Israel and South Africa over a six-year period to assess the safety and efficacy of dirithromycin in the treatment of a variety of acute infectious illnesses, and to compare it with structurally related antibiotics (erythromycin base, roxithromycin, and miocamycin) given orally. A total of 7437 patients have been enrolled from a total of 66 studies and trials, 4263 (57.3%) treated with dirithromycin and 3174 (42.7%) treated with a comparator antibiotic. Patients received either 500 mg dirithromycin (two tablets once daily), 1000 mg erythromycin base (250 mg qid), 300 mg roxithromycin (150 mg bid), or 1200 miocamycin (600 mg bid); the length of therapy ranged from 7 to 14 days. These studies have shown that dirithromycin has a safety profile similar to the comparator agents. The most frequently reported adverse events for both dirithromycin and comparator treatment groups were gastrointestinal in nature. The majority (99%) of adverse events reported from patients treated with dirithromycin were considered mild or moderate in severity. Early discontinuation of antibiotic therapy was infrequent (3-4%) in both treatment groups, and considered to be possibly drug-related in 2-3% of the population. The safety profile of dirithromycin in elderly patients was comparable to that recorded in the overall patient population. The incidence and nature of abnormal clinical laboratory evaluation were similar in dirithromycin and comparator groups. Notable alterations in laboratory tests of haematological or hepatic function were infrequent and were not associated with clinical manifestations. Routine monitoring of standard clinical laboratory tests in patients prescribed dirithromycin does not appear to be necessary. PMID- 8478310 TI - Dirithromycin disc susceptibility tests: interpretative criteria and quality control parameters. AB - Dirithromycin and its bioactive metabolite (erythromycylamine) were compared in vitro to erythromycin against 450 bacterial isolates. Dirithromycin and erythromycylamine did not differ in their in-vitro activity and the two compounds were additive when combined in equal proportions. Both compounds were active against erythromycin-susceptible bacteria but erythromycin was two to four times more potent on a weight-to-weight basis. Interpretive criteria for dirithromycin were not based on achievable blood concentrations since tissue concentrations may be 20-30 times greater than peak serum levels. Dirithromycin-susceptible strains were those with zones > or = 19 mm in diameter (15 micrograms dirithromycin disc) or MIC < or = 2.0 mg/L and resistance was defined as a zone < or = 15 mm or MIC > or = 8.0 mg/L. Interpretive criteria for testing Haemophilus influenzae on Haemophilus Test Medium (HTM) agar were not defined because of the drug's poor activity in the test system used. Two multi-laboratory studies were also undertaken, one to define quality control limits for disc diffusion tests and the other to define broth microdilution MIC control limits for tests with dirithromycin. PMID- 8478311 TI - In-vitro activity of dirithromycin in comparison with other new and established macrolides. AB - Improvements with regard to the in-vitro activity of new macrolides are marginal and apply mainly to Haemophilus spp., Moraxella catarrhalis and Neisseria gonorrhoeae (e.g. azithromycin is two to eight times more active than erythromycin) and to non-enterococcal streptococci (e.g. clarithromycin is two to four times more active than erythromycin). The increase in activity against staphylococci is even less striking, being restricted to a few species and limited to clarithromycin (twice as active as erythromycin). The Enterobacteriaceae, as well as glucose non-fermenting Gram-negative bacilli, remain outside the therapeutic range of the new macrolides, as they were for the established compounds. The majority of enterococci and Corynebacterium jeikeium are resistant to all macrolides, whereas Corynebacterium diphtheriae is highly susceptible. In-vitro susceptibilities both of Campylobacter jejuni/coli and Helicobacter pylori indicate only moderate susceptibility to macrolides and the azalide. In the case of anaerobic organisms, clarithromycin is the most active macrolide against the majority of species. Dirithromycin, clarithromycin, roxithromycin and josamycin, and the azalide azithromycin, are similar in their antibacterial spectrum to erythromycin. New macrolides differ from established compounds largely in their pharmacokinetic behaviour and only minor progress has been achieved in improving their antibacterial spectrum. PMID- 8478312 TI - Modulation of human polymorphonuclear neutrophil function by macrolides: preliminary data concerning dirithromycin. AB - Polymorphonuclear neutrophils (PMN) play a prominent role in the host response to infectious diseases. One major bactericidal mechanism used by these cells is the production of reactive oxygen species during what is referred to as the oxidative burst. However, excessive oxidant generation can also be involved in cell and tissue damage associated with severe inflammatory reactions. Macrolide antibiotics are able to penetrate and concentrate within phagocytes and have been successfully used to treat infections due to facultative intracellular pathogens. However, intracellular accumulation of macrolides with possible alkalinization of cellular compartments may interfere with normal cell function. In-vitro and ex vivo data suggest that macrolides affect various phagocytic functions. This paper presents an overview of the published data concerning the modulation of neutrophil function by macrolides. Preliminary data concerning the in-vitro modulation of the neutrophil oxidative burst by dirithromycin and its metabolite, erythromycylamine, are also discussed. PMID- 8478313 TI - Pharmacokinetics of dirithromycin. AB - Dirithromycin is a new member of the macrolide class of antibiotics and has been developed for oral administration. Dirithromycin is a 14-membered lactone ring macrolide and is the C9-oxazine derivative of erythromycylamine. The human pharmacokinetics and clinical pharmacology of dirithromycin have been studied. Dirithromycin has unique pharmacokinetics which distinguish it from erythromycin. In man, following an oral 500 mg dose of dirithromycin, a mean peak plasma concentration (Cmax) of 0.48 mg/L (range 0.1-1.97) was observed at 4 h. The mean area under the plasma concentration versus time curve (AUC0-24h) measured 3.37 mg.h/L (range 0.39-17.16). No plasma accumulation was observed with multiple-dose administration. Dirithromycin may be taken without regard to meals, although food and H2-receptor antagonists may increase the systemic bioavailability in some patients. Based upon drug interaction studies performed with antipyrine and theophylline, dirithromycin has shown less potential to interact with other drugs metabolized by the cytochrome P450 system that does erythromycin. Plasma concentrations and AUCs were low due to rapid movement of the drug from the vascular space to the extravascular compartment, as reflected by tissue concentrations, which exceeded plasma concentrations 4 h after dosing. Dirithromycin achieves relatively high tissue concentrations (approximately 0.8 5.0 mg/kg) 4-24 h after dosing. The extensive tissue penetration is reflected in a large mean apparent volume of distribution of 800 L (range 504-1041). Dirithromycin is rapidly converted by non-enzymatic hydrolysis during absorption to erythromycylamine, which is microbiologically active. In a 14C-radiolabelled study, 60-90% of the administered dose was hydrolysed to erythromycylamine within 35 min of infusion. After 1.5 h, conversion to erythromycylamine in serum was virtually complete. Plasma protein binding was determined to be 15-30% by ultracentrifugation. Dirithromycin is characterized by a plasma elimination half life of 44 h (range 16-65 h) that permits once-daily administration. Total body clearance was 226-1040 mL/min in the 14C-radiolabelled study. The primary route of elimination of dirithromycin/erythromycylamine was faecal/hepatic. Following intravenous administration, approximately 17-25% of the radioactivity appeared in the urine and 62-81% appeared in the stool, indicating predominantly hepatic excretion. With oral administration 1.2-2.9% of the radioactivity appeared in the urine and 81-97% in the stool. The major part of urinary excretion occurs within the first 48 h post-administration; however, urinary excretion of radioactivity lasted longer than 240 h. The absolute bioavailability calculated from dose corrected urinary excretion data was 10% (6-14%). PMID- 8478314 TI - Tissue distribution of dirithromycin: comparison with erythromycin. AB - In order to ensure effective in-vivo activity, high antibiotic concentrations need to be achieved rapidly at the site of the infection and effective post dosage concentrations should be maintained. Dirithromycin, a new macrolide antibiotic, is converted in vivo to erythromycylamine, which has antimicrobial activity similar to that of the parent compound and a half-life of 20-50 h which allows for once-daily dosing. Both dirithromycin and erythromycylamine are released slowly from the tissue compartment and the major route of elimination is hepatic/faecal: approximately 10% of an oral dose is absorbed and rapidly leaves the circulation to localize in tissues. Dirithromycin and erythromycylamine achieve lung parenchyma concentrations of 1.58-3.81 mg/kg depending on the number of doses administered. Tissue concentrations are significantly higher than simultaneous serum concentrations. Studies in both healthy and pathological lung tissues have shown that significant antibiotic concentrations remain in the tissue 12 and 24 h post-dose. The presence of an inflammatory exudate, especially the phagocytic component, probably contributes to the increased local concentration of dirithromycin found in pathological tissues. The ability of macrolides to concentrate within phagocytes and alveolar macrophages accounts for the observed high lung tissue concentrations of dirithromycin. Dirithromycin also effectively penetrates bronchial secretions: concentrations of 1.04 mg/L 3 h and 1.3 +/- 1.5 mg/L 12 h after a single 250 mg dose. Following a single dose of 500 mg dirithromycin, bronchial mucosa concentrations of > 1.0 mg/kg were detected at 4-24 h post-dose; after multiple doses, concentrations increased to 1.30 mg/kg at 12 h post-dose. Single and multiple 500 mg doses resulted in mean nasal mucosa concentrations of 0.59 +/- 0.17 and 1.86 +/- 0.54 mg/kg (multiple dose) at 24 and 12 h, respectively. Administration of single oral doses of 500 mg 12 or 24 h before tonsillectomy resulted in 24 h post-dosing tonsillar concentrations of 0.60 +/- 0.55 mg/kg (56% of the 12 h concentrations) while doses of 1000 mg/day for two days, resulted in tonsillar antibiotic concentrations of 1.37 +/- 0.55 mg/kg which were maintained for 24 h after the last dose. Dirithromycin also penetrates prostatic tissue with concentrations of 4.1-6.5 mg/kg achieved 15-17 h after the second of two 500 mg doses. In conclusion, dirithromycin exhibits good tissue distribution within selected tissues, is rapidly distributed and persists in significant concentrations up to 24 h post-dose. These studies suggest that dirithromycin has an extremely large volume of distribution. PMID- 8478315 TI - Dirithromycin in the treatment of streptococcal pharyngitis. AB - A double-blind, double-dummy, randomized, multicentre study compared the safety and the efficacy of dirithromycin (two 250 mg tablets, once daily) to erythromycin base (four 250 mg tablets, four times daily) for ten days in the treatment of proven group A beta-haemolytic (GABHs) streptococcal pharyngitis. Five-hundred and fifty-three patients (265 dirithromycin, 288 erythromycin) were enrolled in the trial and analysed for efficacy and safety. Clinical and bacteriological evaluations were performed pre-therapy, during therapy (days 3 5), post-therapy (three to five days after completion of treatment), and late post-therapy (three to five weeks after treatment). All patients qualified for safety analysis. A negative pre-therapy culture was the predominant reason a patient did not qualify for analysis of efficacy. At post-therapy, favourable clinical responses (cure or improvement) were reported for 94.1% (159/169) of dirithromycin and 94.6% (158/167) of erythromycin patients who qualified for efficacy analysis. Post-therapy throat cultures were negative for GABH streptococci in 79.3% (134/169) of dirithromycin patients and 86.2% (144/167) of patients treated with erythromycin (P = 0.314). At late post-therapy 87.6% (134/153) of dirithromycin and 88.7% (134/151) of erythromycin patients reported a favourable clinical response; pathogens were absent in 69.9% (107/153) of dirithromycin and 86.1% (130/151) of erythromycin patients (P = 0.001). The adverse event profile of the two drugs was comparable although digestive and cutaneous adverse events were reported more frequently in the erythromycin treatment group. In this study, more dirithromycin patients had throat cultures positive for GABH streptococci at late post-therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478316 TI - Clinical efficacy of dirithromycin in pharyngitis and tonsillitis. AB - A total of 193 patients with streptococcal pharyngitis/tonsillitis received 500 mg dirithromycin once daily and 196 patients 250 mg erythromycin four times daily for ten days in a double-blind, parallel-group multicentre study. In the dirithromycin treatment group, 97 (50.3%) patients completed the study and were evaluated for efficacy analysis, and 99/196 (50.5%) erythromycin-treated were evaluated for efficacy of treatment. Favourable clinical responses to treatment (cure or improvement of symptoms) at the post-therapy visit (three to five days after therapy completion) occurred in 89 (91.7%) dirithromycin- and 93 (93.9%) erythromycin-treated patients. Bacteriological response was favourable (pathogen eliminated in 81 (83.5%) dirithromycin- and 87 (87.9%) erythromycin-treated patients. At late post-therapy (three to five weeks after treatment) 82/89 (92.1%) dirithromycin- and 90/93 (96.8%) erythromycin-treated patients had a favourable clinical response. Bacteriological response at late post-therapy was favourable in 77 (86.5%) dirithromycin- and 85 (94.4%) erythromycin-treated patients. No deaths occurred during or after treatment, and the serious events experienced by three dirithromycin- and one erythromycin-treated patients were unrelated to treatment. Five patients taking dirithromycin and seven taking erythromycin discontinued treatment prematurely, mainly due to gastrointestinal disturbances. Adverse events that occurred in 2% or more of patients in each treatment group were mainly gastrointestinal (diarrhoea, abdominal pain, nausea and vomiting); headache and rash were also reported. No significant differences in clinical laboratory data were detected that were considered to be drug related. PMID- 8478317 TI - Protein-protein communication within the transcription apparatus. PMID- 8478318 TI - Cloning and nucleotide sequence of the Bacillus subtilis ansR gene, which encodes a repressor of the ans operon coding for L-asparaginase and L-aspartase. AB - Previous work has shown that expression of the Bacillus subtilis ans operon which codes for L-asparaginase and L-aspartase, is both increased and made insensitive to repression by NH4+ by the aspH1 mutation. In current work, the gene in which the aspH1 mutation resides has been identified and sequenced; this gene, termed ansR, is immediately upstream of, but transcribed in the opposite direction from, the ans operon. The promoter region of ansR contains -10 and -35 sequences similar to those recognized by RNA polymerase containing the major vegetative cell sigma factor sigma A, and ansR appears to be monocistronic. The ansR gene codes for a 116-residue protein, but the aspH1 mutant allele has an additional guanine residue at codon 55, resulting in generation of a truncated polypeptide of only 58 residues. Insertional inactivation of ansR resulted in a phenotype identical to that of the aspH1 mutant. The predicted amino acid sequence of the ansR gene product (AnsR) was homologous to that of the repressor of B. subtilis prophage PBSX, and a helix-turn-helix motif, characteristic of many DNA-binding proteins, was present in the AnsR amino-terminal region. These results suggest that ansR codes for a repressor of the ans operon. PMID- 8478319 TI - Cloning and characterization of the Escherichia coli K-12 rfa-2 (rfaC) gene, a gene required for lipopolysaccharide inner core synthesis. AB - A genetically defined mutation, designated rfa-2, results in altered lipopolysaccharide (LPS) biosynthesis. rfa-2 mutants produce a core-defective LPS that contains lipid A and a single sugar moiety, 2-keto-3-deoxyoctulosonic acid, in the LPS core region. Such LPS core-defective or deep-rough (R) mutant structures were previously designated chemotype Re. Phenotypically, rfa-2 mutants exhibit increased permeability to a number of hydrophilic and hydrophobic agents. By restriction analyses and complementation studies, we clearly defined the rfa-2 gene on a 1,056-bp AluI-DraI fragment. The rfa-2 gene and the flanking rfa locus regions were completely sequenced. Additionally, the location of the rfa-2 gene on the physical map of the Escherichia coli chromosome was determined. The rfa-2 gene encodes a 36,000-dalton polypeptide in an in vivo expression system. N terminal analysis of the purified rfa-2 gene product confirmed the first 24 amino acid residues as deduced from the nucleotide sequence of the rfa-2 gene coding region. By interspecies complementation, a Salmonella typhimurium rfaC mutant (LPS chemotype Re) is transformed with the E. coli rfa-2+ gene, and the transformant is characterized by wild-type sensitivity to novobiocin (i.e., uninhibited growth at 600 micrograms of novobiocin per ml) and restoration of the ability to synthesize wild-type LPS structures. On the basis of the identity and significant similarity of the rfa-2 gene sequence and its product to the recently defined (D. M. Sirisena, K. A. Brozek, P. R. MacLachlan, K. E. Sanderson, and C. R. H. Raetz, J. Biol. Chem. 267:18874-18884, 1992), the S. typhimurium rfaC gene sequence and its product (heptosyltransferase 1), the E. coli K-12 rfa-2 locus will be designated rfaC. PMID- 8478320 TI - Identification of a novel operon in Lactococcus lactis encoding three enzymes for lactic acid synthesis: phosphofructokinase, pyruvate kinase, and lactate dehydrogenase. AB - The discovery of a novel multicistronic operon that encodes phosphofructokinase, pyruvate kinase, and lactate dehydrogenase in the lactic acid bacterium Lactococcus lactis is reported. The three genes in the operon, designated pfk, pyk, and ldh, contain 340, 502, and 325 codons, respectively. The intergenic distances are 87 bp between pfk and pyk and 117 bp between pyk and ldh. Plasmids containing pfk and pyk conferred phosphofructokinase and pyruvate kinase activity, respectively, on their host. The identity of ldh was established previously by the same approach (R. M. Llanos, A. J. Hillier, and B. E. Davidson, J. Bacteriol. 174:6956-6964, 1992). Each of the genes is preceded by a potential ribosome binding site. The operon is expressed in a 4.1-kb transcript. The 5' end of the transcript was determined to be a G nucleotide positioned 81 bp upstream from the pfk start codon. The pattern of codon usage within the operon is highly biased, with 11 unused amino acid codons. This degree of bias suggests that the operon is highly expressed. The three proteins encoded on the operon are key enzymes in the Embden-Meyerhoff pathway, the central pathway of energy production and lactic acid synthesis in L. lactis. For this reason, we have called the operon the las (lactic acid synthesis) operon. PMID- 8478321 TI - Deletion analysis of the avermectin biosynthetic genes of Streptomyces avermitilis by gene cluster displacement. AB - Streptomyces avermitilis produces a group of glycosylated, methylated macrocyclic lactones, the avermectins, which have potent anthelmintic activity. A homologous recombination strategy termed gene cluster displacement was used to construct Neor deletion strains with defined endpoints and to clone the corresponding complementary DNA encoding functions for avermectin biosynthesis (avr). Thirty five unique deletions of 0.5 to > 100 kb over a continuous 150-kb region were introduced into S. avermitilis. Analysis of the avermectin phenotypes of the deletion-containing strains defined the extent and ends of the 95-kb avr gene cluster, identified a regulatory region, and mapped several avr functions. A 60 kb region in the central portion determines the synthesis of the macrolide ring. A 13-kb region at one end of the cluster is responsible for synthesis and attachment of oleandrose disaccharide. A 10-kb region at the other end has functions for positive regulation and C-5 O methylation. Physical analysis of the deletions and of in vivo-cloned fragments refined a 130-kb physical map of the avr gene cluster region. PMID- 8478322 TI - Escherichia coli shows two types of behavioral responses to osmotic upshift. AB - Behavioral responses to osmotic upshift were characterized by temporal assays of free-swimming cells of Escherichia coli. Small osmotic upshifts (200 to 300 mosM) elicited tumble responses which were chemotaxis dependent, while large osmotic upshifts (400 to 500 mosM) elicited stopping followed by pseudotumbling which was chemotaxis independent. PMID- 8478323 TI - Proteolytic processing of the protease which initiates degradation of small, acid soluble proteins during germination of Bacillus subtilis spores. AB - Degradation of small, acid-soluble spore proteins during germination of Bacillus subtilis spores is initiated by a sequence-specific protease called GPR. Western blot (immunoblot) analysis of either Bacillus megaterium or B. subtilis GPR expressed in B. subtilis showed that GPR is synthesized at about the third hour of sporulation in a precursor form and is processed to an approximately 2- to 5 kDa-smaller species 2 to 3 h later, at or slightly before the time of accumulation of dipicolinic acid by the forespore. This was found with both normal levels of expression of B. subtilis and B. megaterium GPR in B. subtilis, as well as when either protein was overexpressed up to 100-fold. The sporulation specific processing of GPR was blocked in all spoIII, -IV, and -V mutants tested (none of which accumulated dipicolinic acid), but not in a spoVI mutant which accumulated dipicolinic acid. The amino-terminal sequences of the B. megaterium and B. subtilis GPR initially synthesized in sporulation were identical to those predicted from the coding genes' sequences. However, the processed form generated in sporulation lacked 15 (B. megaterium) or 16 (B. subtilis) amino-terminal residues. The amino acid sequence surrounding this proteolytic cleavage site was very homologous to the consensus sequence recognized and cleaved by GPR in its small, acid-soluble spore protein substrates. This observation, plus the efficient processing of overproduced GPR during sporulation, suggests that the GPR precursor may autoproteolyze itself during sporulation. During spore germination, the GPR from either species expressed in B. subtilis was further processed by removal of one additional amino-terminal amino acid (leucine), generating the mature protease which acts during spore germination. PMID- 8478324 TI - Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. AB - Biosynthesis of the lantibiotic peptide nisin by Lactococcus lactis NIZO R5 relies on the presence of the conjugative transposon Tn5276 in the chromosome. A 12-kb DNA fragment of Tn5276 including the nisA gene and about 10 kb of downstream DNA was cloned in L. lactis, resulting in the production of an extracellular nisin precursor peptide. This peptide reacted with antibodies against either nisin A or the synthetic leader peptide, suggesting that it consisted of a fully modified nisin with the nisin leader sequence still attached to it. This structure was confirmed by N-terminal sequencing and 1H-nuclear magnetic resonance analysis of the purified peptide. Deletion studies showed that the nisR gene is essential for the production of this intermediate. The deduced amino acid sequence of the nisR gene product indicated that the protein belongs to the family of two-component regulators. The deduced amino acid sequence of NisP, the putative product of the gene upstream of nisR, showed an N-terminal signal sequence, a catalytic domain with a high degree of similarity to those of subtilisin-like serine proteases, and a putative C-terminal membrane anchor. Cell extracts of Escherichia coli overexpressing nisP were able to cleave the nisin precursor peptide, producing active, mature nisin. A similar activation was obtained with whole cells but not with membrane-free extracts of L. lactis strains carrying Tn5276 in which the nisA gene had been inactivated. The results indicate that the penultimate step in nisin biosynthesis is secretion of precursor nisin without cleavage of the leader peptide, whereas the last step is the cleavage of the leader peptide sequence from the fully maturated nisin peptide. PMID- 8478325 TI - Coordinate regulation of siderophore and exotoxin A production: molecular cloning and sequencing of the Pseudomonas aeruginosa fur gene. AB - A 5.9-kb DNA fragment was cloned from Pseudomonas aeruginosa PA103 by its ability to functionally complement a fur mutation in Escherichia coli. A fur null mutant E. coli strain that contains multiple copies of the 5.9-kb DNA fragment produces a 15-kDa protein which cross-reacts with a polyclonal anti-E. coli Fur serum. Sequencing of a subclone of the 5.9-kb DNA fragment identified an open reading frame predicted to encode a protein 53% identical to E. coli Fur and 49% identical to Vibrio cholerae Fur and Yersinia pestis Fur. While there is extensive homology among these Fur proteins, Fur from P. aeruginosa differs markedly at its carboxy terminus from all of the other Fur proteins. It has been proposed that this region is a metal-binding domain in E. coli Fur. A positive selection procedure involving the isolation of manganese-resistant mutants was used to isolate mutants of strain PA103 that produce altered Fur proteins. These manganese-resistant Fur mutants constitutively produce siderophores and exotoxin A when grown in concentrations of iron that normally repress their production. A multicopy plasmid carrying the P. aeruginosa fur gene restores manganese susceptibility and wild-type regulation of exotoxin A and siderophore production in these Fur mutants. PMID- 8478326 TI - The frequency and accuracy of replication past a thymine-thymine cyclobutane dimer are very different in Saccharomyces cerevisiae and Escherichia coli. AB - We have compared the mutagenic properties of a T-T cyclobutane dimer in baker's yeast, Saccharomyces cerevisiae, with those in Escherichia coli by transforming each of these species with the same single-stranded shuttle vector carrying either the cis-syn or the trans-syn isomer of this UV photoproduct at a unique site. The mutagenic properties investigated were the frequency of replicational bypass of the photoproduct, the error rate of bypass, and the mutation spectrum. In SOS-induced E. coli, the cis-syn dimer was bypassed in approximately 16% of the vector molecules, and 7.6% of the bypass products had targeted mutations. In S. cerevisiae, however, bypass occurred in about 80% of these molecules, and the bypass was at least 19-fold more accurate (approximately 0.4% targeted mutations). Each of these yeast mutations was a single unique event, and none were like those in E. coli, suggesting that in fact the difference in error rate is much greater. Bypass of the trans-syn dimer occurred in about 17% of the vector molecules in both species, but with this isomer the error rate was higher in S. cerevisiae (21 to 36% targeted mutations) than in E. coli (13%). However, the spectra of mutations induced by the latter photoproduct were virtually identical in the two organisms. We conclude that bypass and error frequencies are determined both by the structure of the photoproduct-containing template and by the particular replication proteins concerned but that the types of mutations induced depend predominantly on the structure of the template. Unlike E. coli, bypass in S. cerevisiae did not require UV-induced functions. PMID- 8478327 TI - The Escherichia coli heat shock gene htpY: mutational analysis, cloning, sequencing, and transcriptional regulation. AB - We have identified a new heat shock gene, designated htpY, located 700 bp upstream of the dnaK dnaJ operon. We cloned it and showed that it is transcribed clockwise vis-a-vis the Escherichia coli genetic map, in the same direction as the dnaK dnaJ operon. The htpY gene encodes a 21,193-Da polypeptide. Promoter mapping experiments and Northern (RNA) analysis showed that the htpY gene belongs to the classical heat shock gene family, because the transcription from its major promoter is under the positive control of the rpoH gene product (sigma 32) and resembles canonical E sigma 32-transcribed consensus promoter sequences. This conclusion has been strengthened by the construction and analysis of a phtpY-lacZ promoter fusion. Despite the fact that htpY null bacteria are viable, the expression of various E sigma 32 heat shock promoters is significantly decreased, suggesting that HtpY plays an important role in the regulation of the heat shock response. Consistent with this interpretation, overproduction of the HtpY protein results in a generalized increase of the heat shock response in E. coli. PMID- 8478328 TI - Molecular cloning and characterization of the Candida albicans enolase gene. AB - A DNA clone containing the putative Candida albicans enolase gene (ENO1) was isolated from a genomic DNA library. The sequenced insert contained a continuous open reading frame of 1,320 bp. The predicted 440-amino-acid protein is 78 and 76% identical, respectively, to Saccharomyces cerevisiae enolase proteins 1 and 2. Only one enolase gene could be detected in C. albicans genomic DNA by Southern analysis with a homologous probe. Northern (RNA) analysis detected a single, abundant C. albicans ENO1 transcript of approximately 1,600 nucleotides. When cells were grown on glucose, levels of ENO1 mRNA were markedly increased by comparison with ENO1 mRNA levels in cells grown on ethanol, a gluconeogenic carbon source. In contrast to this glucose-mediated transcriptional induction, the carbon source had no dramatic effect on the levels of enolase protein or enzyme activity in the C. albicans strains tested. These results suggest that posttranscriptional mechanisms are responsible for modulating expression of the C. albicans enolase gene. PMID- 8478329 TI - Characterization of a Flavobacterium glutathione S-transferase gene involved reductive dechlorination. AB - The gene pcpC, encoding tetrachloro-p-hydroquinone (TeCH) reductive dehalogenase, was cloned from Flavobacterium sp. strain ATCC 39723 and sequenced. The gene was identified by hybridization with a degenerate oligonucleotide designed from the N terminal sequence of the purified protein. An open reading frame of 747 nucleotides was found, which predicts a translational product of 248 amino acids having a molecular weight of 28,263, which agrees favorably with the sodium dodecyl sulfate-polyacrylamide gel electrophoresis-determined molecular weight of 30,000 reported for the purified protein. The predicted translational product of pcpC matched the N-terminal sequence of the purified protein exactly. From the nucleotide sequence, the protein appears to have a processed formylmethionyl. An Escherichia coli pcpC overexpression clone was shown to produce dichlorohydroquinone and trichlorohydroquinone from TeCH. Protein data base searches grouped the predicted translational sequence of pcpC with two previously reported plant glutathione S-transferases but less significantly with any of the mammalian glutathione S-transferases or the glutathione-utilizing, hydrolytic dechlorinating enzyme from Methylobacterium sp. strain DM4. PMID- 8478330 TI - Detection of an A-factor-responsive protein that binds to the upstream activation sequence of strR, a regulatory gene for streptomycin biosynthesis in Streptomyces griseus. AB - DNA-binding assays using mobility shift polyacrylamide gel electrophoresis revealed the presence of a protein that specifically bound to a restriction fragment -288 to -191 bp upstream from the transcriptional start point of strR, a regulatory gene for streptomycin biosynthesis in Streptomyces griseus. The binding site corresponded to an upstream activation sequence predicted from the results of in vivo promoter assays. The binding was greatly enhanced by 5 mM Mg2+. This binding was detected with the protein source only from the wild-type strain and not from an A-factor-deficient mutant strain. The exogenous supplementation of A-factor to the A-factor-deficient mutant strain caused the appearance of the protein in the DNA-binding assay. A synthetic nucleotide 52 bp in length (region from -293 to -242), which was synthesized on the basis of data obtained from both retardation assays with dissected DNA fragments and in vivo promoter assays, was retarded by the A-factor-dependent protein. In addition to this A-factor-dependent protein, at least three proteins with different recognition site affinities capable of binding to the upstream region of the strR promoter were detected. The binding of one of these proteins to both sides of the upstream activation sequence bound by the A-factor-dependent protein was completely abolished in the presence of ATP and Mg2+ in the incubation mixture. The region bound by these proteins showed anomalous electrophoretic mobility, like that of a bent DNA molecule, which is probably caused by the presence of many blocks consisting of A and T. The region bound by these proteins was found to be transcribed in the orientation opposite to that of strR. PMID- 8478331 TI - Symbiotic nitrogen fixation by a nifA deletion mutant of Rhizobium meliloti: the role of an unusual ntrC allele. AB - In the N2-fixing alfalfa symbiont Rhizobium meliloti, the three sigma 54 (NTRA) dependent positively acting regulatory proteins NIFA, NTRC, and DCTD are required for activation of promoters involved in N2 fixation (pnifHDKE and pfixABCX), nitrogen assimilation (pglnII), and C4-dicarboxylate transport (pdctA), respectively. Here, we describe an allele of ntrC which results in the constitutive activation of the above NTRC-, NIFA-, and DCTD-regulated promoters. The expression and activation of wild-type NTRC occur in response to nitrogen availability, whereas in cells carrying the ntrC283 allele, the NTRC283 protein appears constitutively active and is constitutively expressed. The ntrC283 allele was shown to carry a single mutation resulting in the replacement of an Asp by a Tyr residue in the helix-turn-helix motif of ntrC283. Introduction of the ntrC283 allele into a nifA deletion mutant restores the N2-fixation ability to 70 to 80% of the wild-type level. Thus, the nifA gene is dispensable for symbiotic N2 fixation. PMID- 8478332 TI - Negative regulation of sigma 54-dependent dctA expression by the transcriptional activator DctD. AB - In Rhizobium meliloti, the presence of the C4-dicarboxylate transport protein DctA is required for symbiotic N2 fixation in alfalfa root nodules. Expression of dctA is inducible and is mediated by a sensor and activator gene pair encoded by dctB and dctD. In the presence of C4-dicarboxylates, the DCTB sensor protein is believed to phosphorylate and activate DCTD, which in turn activates transcription at the sigma 54-dependent dctA promoter. Here, we present evidence that in addition to activating dctA transcription, DCTD can also repress expression of dctA. By employing an ntrC allele, ntrC283, whose product appears to activate dctA transcription independently of DCTD, we found that while ntrC283 leads to constitutive dctA expression in the absence of dctB and dctD, in a dctB+ dctD+ ntrC283 background high-level expression of dctA occurred in succinate but not in glucose-grown cells. This result suggested that in uninduced cells, inactive DCTD binds to the dctA promoter and prevents its activation by NTRC283. Consistent with the latter interpretation was the observation that overexpression of DCTD from a plasmid promoter prevents dctA expression and results in a Dct- phenotype. Moreover the Dct- phenotype resulting from the overexpression of dctD was dominant to ntrC283. Results from studies of the ability of ntrC283 to suppress the Dct- phenotype of dctB alleles, together with the finding that the Fix- phenotype of a particular dctB allele was dctD dependent, suggest that in particular dctB alleles, sufficient dctD transcription occurs such that the resulting inactive DCTD prevents activation of dctA transcription by NtrC283 or alternate symbiotic regulators. The latter suggestion is supported by the observation that in symbiosis, R. meliloti strains in which DCTD was overexpressed formed nodules which failed to fix nitrogen. PMID- 8478334 TI - Alpha-keto acids are novel siderophores in the genera Proteus, Providencia, and Morganella and are produced by amino acid deaminases. AB - Growth promotion and iron transport studies revealed that certain alpha-keto acids generated by amino acid deaminases, by enterobacteria of the Proteus Providencia-Morganella group (of the tribe Proteeae), show significant siderophore activity. Their iron-binding properties were confirmed by the chrome azurol S assay and UV spectra. These compounds form ligand-to-metal charge transfer bands in the range of 400 to 500 nm. Additional absorption bands of the enolized ligands at 500 to 700 nm are responsible for color formation. Siderophore activity was most pronounced with alpha-keto acids possessing an aromatic or heteroaromatic side chain, like phenylpyruvic acid and indolylpyruvic acid, resulting from deamination of phenylalanine and tryptophan, respectively. In addition, alpha-keto acids possessing longer nonpolar side chains, like alpha ketoisocaproic acid or alpha-ketoisovaleric acid and even alpha-ketoadipic acid, also showed siderophore activity which was absent or negligible with smaller alpha-keto acids or those possessing polar functional groups, like pyruvic acid, alpha-ketobutyric acid, or alpha-ketoglutaric acid. The fact that deaminase negative enterobacteria, like Escherichia coli and Salmonella spp., could not utilize alpha-keto acids supports the view that specific iron-carboxylate transport systems have evolved in members of the tribe Proteeae and are designed to recognize ferric complexes of both alpha-hydroxy acids and alpha-keto acids, of which the latter can easily be generated by L-amino acid deaminases in an amino acid-rich medium. Exogenous siderophores, like ferric hydroxamates (ferrichromes) and ferric polycarboxylates (rhizoferrin and citrate), were also utilized by members of the tribe Proteeae. PMID- 8478333 TI - Bacterioopsin, haloopsin, and sensory opsin I of the halobacterial isolate Halobacterium sp. strain SG1: three new members of a growing family. AB - The genes coding for bacterioopsin, haloopsin, and sensory opsin I of a halobacterial isolate from the Red Sea called Halobacterium sp. strain SG1 have been cloned and sequenced. The deduced protein sequences were aligned to the previously known halobacterial retinal proteins. The addition of these new sequences lowered the number of conserved residues to only 23 amino acids, or 8% of the alignment. Data base searches with two highly conserved peptides as well as with an alignment profile yielded no significant similarity to any other protein, so the halobacterial retinal proteins should be regarded as a distinct protein family. The protein alignment was used to make predictions about the structure of the retinal proteins as well as about the amino acids in contact with retinal proteins. These results were in excellent agreement with the structural model of bacteriorhodopsin of Halobacterium halobium as well as with mutant studies, indicating that (i) structure predictions based on the sequences of a membrane protein family can be quite accurate; (ii) halorhodopsin and sensory rhodopsin I have tertiary structures similar to that of bacteriorhodopsin; (iii) conserved amino acids do not take part in reactions specific for one group of proteins, e.g., proton translocation for bacteriorhodopsins, but have a crucial role in determining the conformation and reactions of the chromophore; and (iv) the general mode of action (light-induced chromophore and protein movements) is the same for all halobacterial retinal proteins, ion pumps as well as sensors. PMID- 8478335 TI - Low-molecular-weight thiols in streptomycetes and their potential role as antioxidants. AB - The intracellular low-molecular-weight thiols present in five gram-positive Streptomyces species and one Flavobacterium species were analyzed by high performance liquid chromatography after fluorescence labeling with monobromobimane. Bacteria were chosen to include penicillin and cephalosporin beta-lactam producers and nonproducers. No significant amount of glutathione was found in any of the streptomycetes. Major intracellular thiols in all strains examined were cysteine, coenzyme A, sulfide, thiosulfate, and an unknown thiol designated U17. Those streptomycetes that make beta-lactam antibiotics also produce significant amounts of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), a key intermediate in their biosynthesis. In Streptomyces clavuligerus, a potent producer of beta-lactams, the level of ACV was low during the early phase of growth and increased rapidly toward the end of exponential growth, paralleling that of antibiotic production. These and other observations indicate that ACV does not function as a protective thiol in streptomycetes. U17 may have this role since it was the major thiol in all streptomycetes and appeared to occur at levels about 10-fold higher than those of the other thiols measured, including ACV. Purification and amino acid analysis of U17 indicated that it contains cysteine and an unusual amine that is not one of the common amino acids. This thiol is identical to an unknown thiol found previously in Micrococcus roseus and Streptomyces griseus. A high level of ergothioneine was found in Streptomyces lactamdurans, and several unidentified thiols were detected in this and other streptomycetes. PMID- 8478336 TI - A cluster of three genes (dapA, orf2, and dapB) of Brevibacterium lactofermentum encodes dihydrodipicolinate synthase, dihydrodipicolinate reductase, and a third polypeptide of unknown function. AB - The dapA and dapB genes, encoding, respectively, dihydrodipicolinate synthase and dihydrodipicolinate reductase, the two first enzymes of the lysine branch of the aspartic amino acid family, were cloned from the DNA of the amino acid-producing bacterium Brevibacterium lactofermentum. The two genes were clustered in a 3.5-kb Sau3AI-BamHI fragment but were separated by an open reading frame of 750 nucleotides. The protein encoded by this open reading frame had little similarity to any protein in the data banks, and its function remains unknown. The three genes were translated in Escherichia coli, giving the corresponding polypeptides. PMID- 8478337 TI - Identification of a phosphoenolpyruvate:fructose phosphotransferase system (fructose-1-phosphate forming) in Listeria monocytogenes. AB - Listeria monocytogenes is a gram-positive bacterium whose carbohydrate metabolic pathways are poorly understood. We provide evidence for an inducible phosphoenolpyruvate (PEP):fructose phosphotransferase system (PTS) in this pathogen. The system consists of enzyme I, HPr, and a fructose-specific enzyme II complex which generates fructose-1-phosphate as the cytoplasmic product of the PTS-catalyzed vectorial phosphorylation reaction. Fructose-1-phosphate kinase then converts the product of the PTS reaction to fructose-1,6-bisphosphate. HPr was shown to be phosphorylated by [32P]PEP and enzyme I as well as by [32P]ATP and a fructose-1,6-bisphosphate-activated HPr kinase like those found in other gram-positive bacteria. Enzyme I, HPr, and the enzyme II complex of the Listeria PTS exhibit enzymatic cross-reactivity with PTS enzyme constituents from Bacillus subtilis and Staphylococcus aureus. PMID- 8478338 TI - Large-scale recrystallization of the S-layer of Bacillus coagulans E38-66 at the air/water interface and on lipid films. AB - S-layer protein isolated from Bacillus coagulans E38-66 could be recrystallized into large-scale coherent monolayers at an air/water interface and on phospholipid films spread on a Langmuir-Blodgett trough. Because of the asymmetry in the physiochemical surface properties of the S-layer protein, the subunits were associated with their more hydrophobic outer face with the air/water interface and oriented with their negatively charged inner face to the zwitterionic head groups of the dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylethanolamine (DPPE) monolayer films. The dynamic crystal growth at both types of interfaces was first initiated at several distant nucleation points. The individual monocrystalline areas grew isotropically in all directions until the front edge of neighboring crystals was met. The recrystallized S-layer protein and the S-layer-DPPE layer could be chemically cross-linked from the subphase with glutaraldehyde. PMID- 8478339 TI - The cortical peptidoglycan from spores of Bacillus megaterium and Bacillus subtilis is not highly cross-linked. AB - Determination by amino acid analyses of the percentage of diaminopimelic acid in the spore cortex of Bacillus megaterium and Bacillus subtilis which is involved in interpeptide cross-links gave values of 31 to 37%. This finding supports the idea that the cortex volume could undergo significant changes in response to changes in pH or ionic strength and could thus play an active role in reducing the water content of the spore protoplast during sporulation. PMID- 8478340 TI - Altered muropeptide composition in Staphylococcus aureus strains with an inactivated femA locus. AB - Tn551 inactivation of femA, a factor involved in methicillin resistance of Staphylococcus aureus, caused the production of peptidoglycan in which the fraction of monoglycyl- and serine-containing muropeptides was increased at the expense of pentaglycyl muropeptides. femA mutants have a specific block in the biosynthesis of pentaglycine cross bridges after the addition of the first glycine residue. PMID- 8478341 TI - Cell division and transcription of ftsZ. AB - For normal cell division, the ftsZ gene must be transcribed from a number of promoters that are located within the proximal upstream genes (ddlB, ftsQ, and ftsA). We show that the main promoters have identical responses to changes in growth rate, i.e., under all conditions, the frequency of transcription per septum formed is approximately constant and independent of cell size or growth rate per se. We also show that transcription from these promoters is independent of stationary-phase transcription factor sigma s. PMID- 8478342 TI - ESB Research Award 1992. The mechanism of bone remodeling and resorption around press-fitted THA stems. AB - A major problem threatening the long-term integrity of total hip replacement is the loss of proximal bone often found around noncemented stems in the long term. It is generally accepted that 'stress shielding' is the cause for this problem: after implantation of the prosthesis the surrounding bone is partially 'shielding' from load carrying and starts to resorb. One of the proposed answers to this problem is the application of press-fitted stems. These smooth-surfaced implants are thought to provoke higher proximal bone loading, and, hence, less stress shielding than bonded implants, because they are wedged into the femur every time when loaded. However, in a two-year experiment in dogs, similar amounts of resorption of the proximal cortex were found around press-fitted and bonded implants. The question arises how similar resorption patterns can develop under completely different stress conditions, and whether this phenomenon can be explained by adaptive bone remodeling theories based on Wolff's law. In the present study an answer was sought for this question. An advanced iterative computer simulation model was used to analyze the remodeling process in the animal experiment. Three-dimensional finite element models were constructed from the animal experimental configuration, in which smooth, press-fitted stems were applied unilaterally in the canine. The FE model was integrated with iterative remodeling procedures, validated in earlier studies. In the model an appropriate non-linear representation of the loose bone-implant interface was realized, also capable of simulating the proximal interface gap that was found around the uncoated implants. The simulation models predicted similar amounts of proximal bone loss and distal bone densification as found in the animal model. Hence, the cortical bone loss could indeed be predicted by the strain-adaptive bone remodeling theory. By unraveling the simulation process, the question stated above could be answered. Densification of the distal bone bed during the initial remodeling process was found to cause reduced axial stem displacement (elastic subsidence), decreasing the wedging effect of the stem and, hence, decreasing the loading of the proximal bone, resulting in proximal bone loss. Hence, whereas in the case of bonded stems the proximal resorption process develops monotonously to a new equilibrium, the process around smooth, press-fitted stems develops nonmonotonously. This is due primarily to the unbonded interface conditions and the development of a proximal fibrous membrane. The remodeling process then gradually causes the stem to be jammed in the distal diaphyses (proximal 'stress bypass'). PMID- 8478343 TI - Errors in the estimation of arterial wall shear rates that result from curve fitting of velocity profiles. AB - An analysis was performed to determine the error that results from the estimation of the wall shear rates based on linear and quadratic curve-fittings of the measured velocity profiles. For steady, fully developed flow in a straight vessel, the error for the linear method is linearly related to the distance between the probe and the wall, dr1, and the error for the quadratic method is zero. With pulsatile flow, especially a physiological pulsatile flow in a large artery, the thickness of the velocity boundary layer, delta is small, and the error in the estimation of wall shear based on curve fitting is much higher than that with steady flow. In addition, there is a phase lag between the actual shear rate and the measured one. In oscillatory flow, the error increases with the distance ratio dr1/delta and, for a quadratic method, also with the distance ratio dr2/dr1, where dr2 is the distance of the second probe from the wall. The quadratic method has a distinct advantage in accuracy over the linear method when dr1/delta << 1, i.e. when the first velocity point is well within the boundary layer. The use of this analysis in arterial flow involves many simplifications, including Newtonian fluid, rigid walls, and the linear summation of the harmonic components, and can provide more qualitative than quantitative guidance. PMID- 8478344 TI - Do bone ingrowth processes produce a globally optimized structure? AB - A topology optimization program was applied to test the hypothesis that bone adaptation to porous coated implants produces a structure which minimizes the global strain energy density. The program was used to predict the optimal material layout around a porous coated tibial component with multiple cones [Goldstein et al., Trans. 37th ORS, p. 92 (1991)]. The sensitivity of the predicted adaptation to analysis assumptions was assessed and the predicted bone ingrowth and apposition were compared with the experimental findings of Goldstein et al. The results showed that apposition occurred consistently at the cone tips regardless of analysis assumptions. The specific topology of apposition at the cone tips was most sensitive to the assumed loading conditions. A comparison with the experimental results for 11 subdivisions showed that the general predicted location of material agreed with the experimental results (R2 > or = 0.59). However, the program predicted a consolidated bone greater than 1000 microns in thickness at the cone tips, which differed from the porous bone structure found experimentally. This discrepancy was reflected in a refined comparison over 31 subdivisions which did not produce a significant correlation (R2 < or = 0.3). The program also predicted little ingrowth (< 6-7%), indicating that ingrowth past the first bead layer contributed little to the overall bone-implant interface layer stiffness. Based on these results, we conclude, within limitations of a two dimensional analysis, that bone adaptation to porous coated implants does not produce a structure solely optimized to minimize the global strain energy density. We hypothesize that the final bone structure reflects the need to meet both mechanical and nutritional demands. PMID- 8478345 TI - Nonstationary properties of postural sway. AB - Postural sway during quite stance is usually assumed to be a stationary stochastic process. We tested this assumption by investigating the time invariance of the average value and variance of the postural sway of three subjects. The sway was measured with a force plate under three conditions: subject standing on two feet with eyes open; subject standing on two feet with eyes closed; and subject standing on one foot with eyes open. Data were collected in 1 min runs. More than 50 min of data were collected for each subject under each test condition. The data were averaged across all runs for each subject and condition. Trends were found to be present in the data. In addition, there were initial transient increases in the second-order moments about the trends. The transient changes in first- and second-order moments usually disappeared during the first 20 s. In light of these findings, we can reject the hypothesis that postural sway is a stationary process. The results imply that the usual methods to parameterize postural sway have to be either changed or reinterpreted. PMID- 8478346 TI - Geometric properties and the predicted mechanical behavior of adult human clavicles. AB - An image processing system was used to examine histomorphometric properties of 15 adult male and female human clavicles. Variations in porosity, cross-sectional area, anatomic and principal moments of inertia were assessed at 2.5-5.0% increments along the length of the clavicles. The clavicle's biomechanical behavior (axial, flexural, and torsional rigidities and the critical force for buckling) was modeled from these data using beam theory. Over threefold variations in porosity and moments of inertia were found along the length of the s-shaped clavicle--the greatest porosity and moments of inertia were located in the variably shaped sternal and acromial thirds of the bone in contrast to the denser and smaller, more circulatory shaped central third of the bone. Clavicle orientation, as indicated by the direction of greatest resistance to bending (maximum principal moment of inertia), was found to rotate from a primarily cranio-caudal orientation at the sternum to a primarily anterior-posterior orientation at the acromion. Based on cross-sectional geometry, section moduli, and estimates of flexural and torsional rigidity, the clavicle was found to be weakest in the central third of its length. These data concur with the fracture location most commonly reported clinically. Analysis of Euler buckling predicted a minimum critical force for buckling during axial loading of approximately two to three body weights for an average adult. Thus, buckling, or a combination of axial loading and bending or torsional loading, must be considered as possible failure mechanisms for this commonly injured bone. PMID- 8478347 TI - Experimental measurement of ligament force, facet force, and segment motion in the human lumbar spine. AB - Facet forces, longitudinal ligament loads, and vertebral body motion were experimentally measured in five fresh human lumbar spine segments, L1-L2. Strain gages on the bone surface were used to quantify facet loads. Buckle transducers were used to measure anterior and posterior longitudinal ligament loads. The three-dimensional motion of the motion segment was measured with an instrumented spatial linkage. The facets were found to carry no load in flexion, large loads during extension (205 N at a 10 Nm moment and a 190 N axial load), torsion (65 N at a 10 Nm moment and a 150 N axial load), and lateral bending (78 N at a 3 Nm moment and a 160 N axial load). The facet contact site on the inferior articular process of L1 was found to move inferiorly to a position of tip impingement near the lamina as extension moments increased. Impingement occurred in the range of 4 6 Nm extension. The posterior and anterior longitudinal ligaments were predominantly loaded in flexion and extension, respectively. No ligament loads occurred in lateral bending and torsion. A 1 cm strip of the anterior longitudinal ligament carried loads up to 130 N at the largest extension moment of 11.4 Nm. The posterior longitudinal ligament had a 60 N load at the largest flexion moment of 7.1 Nm. There was no pre-load in the ligament detectable with the buckle transducers (> 4 N). The facets and ligaments began carrying load immediately with applied load, without a lax region. The experimental technique developed and used provides a good tool for obtaining simultaneous facet joint loads, ligament loads, and vertebral body motion without altering the motion segment. PMID- 8478348 TI - On the viscoelastic properties of the anteromedial bundle of the anterior cruciate ligament. AB - The nonlinear viscoelastic properties of the anteromedial (AM) bundle of porcine anterior cruciate ligament (ACL) were characterized by using a new analytical approach based on the quasi-linear viscoelastic theory. Stress relaxation and cyclic tensile tests were performed. Using the solution derived from this approach, we curve-fitted data from the stress relaxation test to determine the viscoelastic coefficients for the ligament bundles. The coefficients were verified by comparison of the predicted and the experimental results from the cyclic tensile test. The ACL AM bundle exhibited significant stress relaxation with time; a reduction of more than 50% of the peak value occurred during the 2-h experiment. Also, the reduced relaxation function for the ACL AM bundle was not a linear function of logarithmic time, as is commonly assumed for many soft tissues. The new approach, which takes into account the finite strain rate of the ramp function used in the stress relaxation test, provides an accurate description of this nonlinear stress relaxation behavior. PMID- 8478349 TI - Compressive fatigue behavior of bovine trabecular bone. AB - We studied the fatigue behavior of bovine trabecular bone specimens under stress control using a sinusoidal uniaxial compressive load profile with a frequency of 2 Hz. The stress range was determined from the corresponding initial global platen-to-platen strain range, where the maximum initial strain was between 0.8 and 2.1% and the minimum strain was 0.6%. The local strain distribution was measured on the same type of specimen by affixing glass spheres and photographing them in the unloaded and loaded positions using multiple exposures. The number of cycles to failure (defined as a 5% decrease in secant modulus) was strongly correlated with the initial global maximum strain (r2 = 0.78) and ranged from 20 cycles at 2.1% strain to 400,000 cycles at 0.8% strain. All of the fatigue specimens showed a region of transverse failure approximately 1 mm from the end of the specimen. Microscopic examination of the failure zones revealed two failure modes: a straight transverse brittle-like fracture through the trabeculae, most often found in trabeculae transverse to the loading direction, and buckling-like failure, common in oblique trabeculae, involving bending and splitting. The local strain increased towards the ends of the specimens to a value 2-4 times that in the middle. Modulus degradation with the number of cycles was distinctively different for high-cycle and low-cycle fatigue, suggesting the possibility that both creep and damage accumulation contribute to fatigue failure of trabecular bone. PMID- 8478350 TI - Relationship between ankle muscle and joint kinetics during the stance phase of locomotion in the cat. AB - The purpose of this study was to examine the relationship between internal force production in selected skeletal muscles and the externally calculated joint moment during overground locomotion in the adult cat. Hindlimb segments were modelled as a linked system of rigid bodies and a generalized muscle moment (GMM), the sum over all active and passive tissues acting about the joint, was calculated using principles of inverse dynamics. Moments produced by individual muscles were calculated using tendon transducers implanted in freely moving cats and muscle moment arm information. Results indicated that the externally measured variables of peak ground reaction force and joint position were equally important to the determination of peak ankle GMM. Examination of peak moments revealed that increases in peak ankle GMM were met by increases in medial (MG) and lateral (LG) gastrocnemius output. Peak soleus (SOL) moments did not change significantly as a function of peak ankle GMM. The role of the plantaris (PLT) was less clear, with peak moments increasing significantly as a function of peak ankle GMM in one cat. All four ankle extensors were important to the attainment of peak ankle GMM early in stance. Subsequently, SOL and PLT contributed substantially to the ankle GMM throughout stance, LG moments declined to near zero, soon after peak ankle GMM; and MG moments demonstrated a substantial but more gradual decline. The relative contributions of these individual muscles to the ankle GMM were supported by their respective architecture, uniarticular versus multiarticular function, and physiological profiles. PMID- 8478351 TI - Effects of hip center location on the moment-generating capacity of the muscles. AB - We have developed a three-dimensional biomechanical model of the human lower extremity to study how the location of the hip center affects the moment generating capacity of four muscle groups: the hip abductors, adductors, flexors, and extensors. The model computes the maximum isometric force and the resulting joint moments that each of 25 muscle-tendon complexes develops at any body position. Abduction, adduction, flexion, and extension moments calculated with the model correspond closely with isometric joint moments measured during maximum voluntary contractions. We used the model to determine (1) the hip center locations that maximize and minimize the moment-generating capacity of each muscle group and (2) the effects of superior-inferior, anterior-posterior, and medial-lateral displacement of the hip center on the moment arms, maximum isometric muscle forces, and maximum isometric moments generated by each muscle group. We found that superior-inferior displacement of the hip center has the greatest effect on the force- and moment-generating capacity of the muscles. A 2 cm superior displacement decreases abduction force (44%), moment arm (12%), and moment (49%), while a 2 cm inferior displacement increases abduction force (20%), moment arm (7%) and moment (26%). Similarly, a 2 cm superior displacement decreases flexion force (27%), moment arm (6%), and moment (22%), while inferior displacement increases all three variables. Anterior-posterior displacement alters the moment-generating capacity of the flexors and extensors considerably, primarily due to moment arm changes. Medial-lateral displacement has a large effect on the moment-generating capacity of the adductors only. A 2 cm medial displacement decreases adduction moment arm (20%), force (26%) and moment (40%). These results demonstrate that the force- and moment-generating capacities of the muscles are sensitive to the location of the hip center. PMID- 8478352 TI - Slow deformation of intervertebral discs. AB - Intervertebral discs exhibit pronounced time-dependent deformations when subjected to load variations. These deformations are caused by fluid flow to and from the disc and by viscoelastic deformation of annulus fibres. The fluid flow is caused by differences between mechanical and osmotic pressure. A mechanical model of lumbar disc functions allows one to calculate both the extent of fluid flow and its implications for disc height as well as the role played by viscoelastic deformation of annulus fibres. From such calculations changes in body height are estimated. Experimental results already documented in the literature offer bases for the determination of the parameters involved. Body height variations are studied, both those related to normal diurnal rhythmicity and those related to somewhat exceptional circumstances. The normal diurnal fluid flow is found to be about +/- 40% of the disc fluid content late in the evening. Viscoelastic deformation of annulus fibres contributes approximately one quarter of the height change obtained after several hours normal activity, but dominates during the first hour. PMID- 8478353 TI - The relationship between EMG activity and extensor moment generation in the erector spinae muscles during bending and lifting activities. AB - The relationship between EMG activity and extensor moment generation in the erector spinae muscles was investigated under isometric and concentric conditions. The full-wave rectified and averaged EMG signal was recorded from skin-surface electrodes located over the belly of the erector spinae at the levels of T10 and L3, and compared with measurements of extensor moment. The effects of muscle length and contraction velocity were studied by measuring the overall curvature (theta) and rate of change of curvature (d theta/dt) of the lumbar spine in the sagittal plane, using the '3-Space Isotrak' system. Isometric contractions were investigated with the subjects pulling up on a load cell attached to the floor. Hand height was varied to produce different amounts of lumbar flexion, as indicated by changes in lumbar curvature. The extensor moment was found to be linearly related to EMG activity, and the 'gradient' and 'intercept' of the relationship were themselves dependent upon the lumbar curvature at the time of testing. Concentric contractions were investigated with the subjects extending from a seated toe-touching position, at various speeds, while the torque exerted on the arm of a Cybex dynamometer was continuously measured. Under these conditions the EMG signal (E) was higher than the isometric signal (E0) associated with the same torque. E and E0 were related as follows: E0 = E/(1 + A d theta/dt), where A = 0.0014 exp (0.045P) and P = percentage lumbar flexion. This equation was used to correct the EMG data for the effect of contraction velocity. The corrected data were then used, in conjunction with the results of the isometric calibrations, to calculate the extensor moment generated by the erector spinae muscles during bending and lifting activities. The extensor moment can itself be used to calculate the compressive force acting on the lumbar spine. PMID- 8478354 TI - Mechanical and textural properties of pelvic trabecular bone. AB - So far, virtually nothing is known about the mechanical properties of pelvic trabecular bone. In this study, several techniques have been used to establish some insight in these properties. Dual-energy quantitative computer tomography (DEQCT) was used to look at the distribution of bone densities throughout the pelvic bone and nondestructive mechanical testing was used to obtain Young's moduli and Poisson's ratios in three orthogonal directions for cubic specimens of pelvic trabecular bone. The same specimens were then used for stereological measurements to obtain volume fractions and the spatial orientations of the mean intercept lengths. The combined data on the mechanical tests and the stereological measurements made it possible to calculate Young's moduli and Poisson's ratios for the specimens' principal material axes. DEQCT showed that bone densities within a pelvic bone are significantly higher in the superior part of the acetabulum, extending to the sacroiliac joint area and, secondly, in the area of the pubic symphysis. Volume fractions found for the specimens did not exceed 20%. This may be considered rather low when compared to values reported in the literature for trabecular bone of femoral or tibial origin, but the values do lie in the same range as vertebral trabecular bone. With the volume fraction as its primary predictor, values of Young's moduli were also low. For most specimens these values were not higher than 100 MPa, with an occasional peak of 250 MPa. Looking at the ratio of the highest and lowest Young's modulus or at the components of the fabric tensor, it can be concluded that pelvic trabecular bone is not highly anisotropic. On an average, Poisson's ratio was found to be closer to 0.2 rather than 0.3, which is in accordance with other studies on Poisson's ratio of trabecular bone. PMID- 8478355 TI - Trunk muscle geometry and centroid location when twisting. AB - The trunk muscles of the lumbar region were studied using magnetic resonance imaging (MRI) in five male volunteers placed in neutral and in two twisted postures. Using a CAD digitizing system, the positions of trunk muscle centroids and the cross-sectional areas of these muscles were measured from the transverse scans at 1 cm intervals from L2 to S1. Muscle lines of action were created by connecting the muscle centroids from the successive sections. Changes in cross sectional areas and displacements of centroids in a three-dimensional coordinate system and the local two-dimensional coordinate system were estimated at each disc level. In the three-dimensional coordinate system, all muscle centroids were displaced when twisting. Thus, the locations and orientations of all muscle lines of action changed. In the local two-dimensional coordinate system, only the muscle centroids of four abdominal muscles were displaced. Most of these displacements occurred in the first 25 degrees of twisting. Higher up in the lumbar spine, the displacement was greater. The changes in moment arms were sometimes as great as twofold. Only the abdominal oblique muscles (AOM) changed their cross-sectional area significantly; the area of the right AOM ipsilateral to the side of twisting increased, while that of the left AOM was decreased. PMID- 8478357 TI - Mechanical responses of the periodontal ligament in the transverse section of the rat mandibular incisor at various velocities of loading in vitro. AB - Stress-strain curves of the periodontal ligament (PDL) were obtained at various velocities of extrusive loading of 1, 10, 10(2), 10(3) and 10(4) mm/24 h in vitro. Significant increases of the maximum shear stress, tangent modulus and failure strain energy density were found with increases in the velocity of loading. The maximum shear strain increased from a velocity of 1 to 10 mm/24 h but decreased from 10 to 10(4) mm/24 h. It was shown histologically that the free surface of the PDL adhering to the cementum after mechanical testing was rough and irregular at higher velocities and rather smooth at lower velocities. These results showed that the mechanical properties and mode of failure of the rat incisor PDL were greatly dependent on the strain rate. It is possible that the PDL of the continuously erupting rat incisor has mechanical characteristics favourable for resisting weakly to slow and small eruptive forces but strongly to the fast and large occlusal forces as suggested previously [Chiba and Komatsu, The Biological Mechanisms of Tooth Eruption and Root Resorption (1988)]. PMID- 8478356 TI - Estimation of muscle forces about the wrist joint during isometric tasks using an EMG coefficient method. AB - A technique for estimating isometric muscle forces based on EMGs and anatomical parameters is presented. In the present study, we record EMGs from five muscles acting at the wrist, during a series of isometric contractions in flexion, extension, ulnar deviation and radial deviation. The method then uses these EMG signals and the necessary anatomical data to estimate individual muscle forces. For one subject, complete anatomical parameters were estimated by MRI reconstruction of muscle moment arms and lines of muscle action. In all subjects, the errors associated with variability in the EMG signals were reduced through the use of signal processing techniques and intensive subject training. These EMG based force estimates were then validated by evaluations at torque directions in which no mechanical redundancy existed. The stability of the solution space was examined using Monte Carlo simulations. The results of our study show that individual muscle forces at the wrist can be estimated with considerable accuracy, without assuming any control strategy (as is done with optimization theories). However, due to the limited mechanical redundancy of the wrist, it is uncertain whether the method can be used to estimate muscle forces in more highly redundant systems. PMID- 8478358 TI - Determination of loading parameters in the canine hip in vivo. AB - The loading parameters in the canine hip were determined from multiple studies, involving the collection of kinematic and force plate data in vivo joint reaction force from an instrumented hip replacement prosthesis, and in vivo femoral cortical bone strain gauge data in different dogs. In the middle of the stance phase of gait the canine femur was flexed 110 degrees with respect to the pelvis and formed a 20 degree angle relative to the floor. At this point in the gait cycle, a line passing from the superior to the inferior aspect of the pubic symphysis was parallel to the floor. The joint reaction force measurements showed that the net force vector during midstance was directed inferiorly, posteriorly, and laterally, with a peak magnitude of up to 1.65 times the body weight. A torsional moment of 1.6 N m is exerted about the femoral shaft. In vivo strain data showed that during gait peak compressive strains of -300 to -502 microstrain were produced on the medial aspect of the femoral cortex and peak tensile strains of +250 to +458 midstrain were produced on the femoral cortex. At the midstance phase of gait, principal cortical bone strains were rotated up to 29 degrees relative to the long axis of the femur, suggesting torsional loads on the femur. These data in combination provide valuable insights on the loading parameters of the canine hip which can be used in future applications of the canine as a model for evaluating mechanically based phenomena such as bone ingrowth and remodeling or hip prostheses. PMID- 8478359 TI - The biphasic poroviscoelastic behavior of articular cartilage: role of the surface zone in governing the compressive behavior. AB - Surface fibrillation of articular cartilage is an early sign of degenerative changes in the development of osteoarthritis. To assess the influence of the surface zone on the viscoelastic properties of cartilage under compressive loading, we prepared osteochondral plugs from skeletally mature steers, with and without the surface zone of articular cartilage, for study in the confined compression creep experiment. The relative contributions of two viscoelastic mechanisms, i.e. a flow-independent mechanism [Hayes and Bodine, J. Biomechanics 11, 407-419 (1978)], and a flow-dependent mechanism [Mow et al. J. biomech. Engng 102, 73-84 (1980)], to the compressive creep response of these two types of specimens were determined using the biphasic poroviscoelastic theory proposed by Mak. [J. Biomechanics 20, 703-714 (1986)]. From the experimental results and the biphasic poroviscoelastic theory, we found that frictional drag associated with interstitial fluid flow and fluid pressurization are the dominant mechanisms of load support in the intact specimens, i.e. the flow-dependent mechanisms alone were sufficient to describe normal articular cartilage compressive creep behavior. For specimens with the surface removed, we found an increased creep rate which was derived from an increased tissue permeability, as well as significant changes in the flow-independent parameters of the viscoelastic solid matrix. permeability, as well as significant changes in the flow-independent parameters of the viscoelastic solid matrix. From these tissue properties and the biphasic poroviscoelastic theory, we determined that the flow-dependent mechanisms of load support, i.e. frictional drag and fluid pressurization, were greatly diminished in cartilage without the articular surface. Calculations based upon these material parameters show that for specimens with the surface zone removed, the cartilage solid matrix became more highly loaded during the early stages of creep. This suggests that an important function of the articular surface is to provide for a low fluid permeability, and thereby serve to restrict fluid exudation and increase interstitial fluid pressurization. Thus, it is likely that with increasing severity of damage to the articular surface, load support in cartilage under compression shifts from the flow-dependent modes of fluid drag and pressurization to increased solid matrix stress. This suggests that it is important to maintain the integrity of the articular surface in preserving normal compressive behavior of the tissue and normal load carriage in the joint. PMID- 8478360 TI - Decomposition of superimposed ground reaction forces into left and right force profiles. AB - The process of collecting ground reaction force data by mounting a forceplate beneath a treadmill belt has the advantage that numerous walking trials can be analyzed without the problem of subjects 'targeting' their footsteps. However, a potential problem is that the measured forces represent a summation of bilateral force profiles during the double support phase of walking. To address this issue, an algorithm is described for decomposing superimposed ground reaction force data into individual left and right profiles. It is based on an examination of the side-to-side oscillations of the measured center of pressure (CoP). Whenever the measured CoP exceeds a certain threshold, it is assumed that the person is being supported by a single limb, and the measured GRF data reflect the forces under that limb. Conversely, when the measured CoP indicates that both feet are on the treadmill, it is assumed that the location of the individual CoP under each foot is given by wL2 and wR2. These quantities reflect the greatest excursion of the measured CoP towards the left and right sides of the forceplate, respectively. With this assumption, individual GRF profiles can be calculated by means of solving two simultaneous equations--one describing the equilibrium of forces in the vertical direction, and one describing the equilibrium of moments about an antero-posterior axis of the forceplate. The algorithm describing this procedure is simple enough to be implemented on a spreadsheet and yields estimates for average force, impulse, peak force and stance time that are typically within 3% of the true values. PMID- 8478361 TI - Theoretical analysis of the experimental artifact in trabecular bone compressive modulus. AB - A theoretical analysis was performed to characterize potential experimental artifacts in conventional compression testing of trabecular bone, where strains are based on the relative displacements of the two loading platens. We assumed that the total experimental artifact for modulus was the sum of a damage and friction artifact and derived equations to describe these artifacts. The two unknown constants in these equations were found using a combination of data derived from linear finite element analyses and in vitro uniaxial compression tests. Subsequent finite element analyses allowed estimation of the artifacts for a wide range of specimens (cube, 1:4-3:1 aspect ratio cylinders). If friction is completely eliminated at the specimen-platen interface, the Young's modulus of a 5 mm sized (1:1 aspect ratio dimension) specimen which has a damage artifact due to machining may be underestimated by at least 45% regardless of specimen geometry; otherwise, the platens modulus may vary from less than 30 to over 175% of the Young's modulus, depending upon the specimen geometry and Poisson's ratio of the bone. Increasing the specimen size reduces the artifact only slightly. Since Poisson's ratio can be large for trabecular bone and is rarely known a priori, the precision of the conventional compression test will, therefore, be poor unless friction is completely eliminated at the specimen-platen interface. However, without friction at the interface, the platens modulus will always underestimate Young's modulus, thereby reducing the accuracy of this test. There was also evidence that the strength may be affected by these artifacts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478362 TI - Measurement of angular displacements using Hall effect transducers. AB - Hall effect transducers were studied as an alternative to limited-wear precision potentiometers and optical encoders in measuring angular displacements. Various design parameters are identified, and the optimum Hall effect transducer configuration is presented. Using this configuration, it was possible to measure an angular rotation of 140 degrees with a standard deviation of 0.5 degrees. Within the +/- 35 degrees mid-range of the total 140 degrees, the standard deviation improved to 0.1 degrees. PMID- 8478363 TI - Calculating the probability that microcracks initiate resorption spaces. AB - This paper explores the assumptions and limitations of the probability calculation that led to the conclusion by Burr et al. (1985) that microcracks initiate new remodeling events. It also corrects several minor errors in the calculation in the original manuscript. The results show that the probability that cracks and resorption spaces are associated depends heavily on a factor, F, that accounts for the possibility that some osteons that contain both a crack and a resorption space share a cement line with an adjacent osteon to which the crack more properly 'belongs.' F in turn depends on (1) the measurement criteria for cracks and resorption spaces, (2) the osteon population density in the bone, and (3) the mechanism by which cracks initiate remodeling. The theoretical maximum number of osteons that can contain both a crack and a resorption space (nmax) increases as the number of resorption spaces (r), the number of cracks (c), and F increase, but decreases as the osteon population density (d) increases. A larger nmax makes a direct association between cracks and resorption spaces more difficult to demonstrate experimentally. PMID- 8478364 TI - A numerical-experimental method for a mechanical characterization of biological materials. AB - For the determination of material parameters, it is a common practice to extract specimens with well-defined geometries. The design of the samples and the choice of the applied load are meant to lead to a homogeneous stress and strain distribution in a part of the sample. When applied to biological materials, this raises a number of problems: homogeneous strains cannot be obtained because the materials have inhomogeneous properties, and the manufacturing of samples is hard or sometimes impossible. In this technical note a different approach is presented, based on the use of a digital image technique for the measurement of nonhomogeneous strain distributions, finite element modeling and the use of a minimum-variance estimator. The method is tested by means of experiments on an orthotropic elastic membrane of a woven and calendered textile. Five parameters are identified using the experimental data of one single experiment. PMID- 8478365 TI - Analysis of birth intervals in India's Uttar Pradesh and Kerala States. AB - Life tables of birth intervals and median birth intervals in two Indian states, Uttar Pradesh and Kerala, were computed for several subgroups of the study population. Multivariate hazards modelling technique was used to examine the net effect of each of the variables studied. The results show a substantial effect of socioeconomic variables in child-spacing after controlling for the major intermediate variables. PMID- 8478366 TI - Emerging patterns of child-spacing in Canada. AB - This study used data from the 1984 Family History Survey conducted by Statistics Canada to examine recent trends and patterns of child-spacing among currently married women. Life table and proportional hazards estimates show that Canadian women, particularly those in younger age groups with higher education and longer work experience, start having children late, but have subsequent children rather quickly. This suggests that such women tend to complete childbearing within a compressed time period. PMID- 8478367 TI - Estimates of adult mortality in Burundi. AB - Adult mortality in Burundi during the 1970s and 1980s is estimated using data from the 1987 Demographic and Health Survey (DHS). Estimates from traditional indirect methods are compared with those from the inter-survey method using data on the number of years since the respondent's parent died. Life expectancy at birth was estimated as 48.55 years for males and 51.23 years for females. PMID- 8478368 TI - Breast-feeding and child health in the United States. AB - This paper evaluates the influence of breast-feeding on infectious and allergic diseases in infants and children through an analysis of data from a large national sample of US children. It controls for a large number of maternal and child health, demographic, and socioeconomic variables which have been shown to affect feeding patterns, and it includes several aspects of the feeding pattern in addition to breast-feeding. The results suggest that breast-feeding provides some protection against pneumonia and otitis media in the United States while early introduction of formula may have a separate and negative effect. PMID- 8478369 TI - Breast-feeding, water and sanitation, and childhood malnutrition in the Philippines. AB - This study examines effects and interactions of socioeconomic status, access to water supply and sanitation, and breast-feeding practices in relation to child growth in two provincial cities in the Philippines. Multivariate analysis identified food expenditure per head, education of the household head and gender of the child as significant predictors of nutritional status. The duration of partial and full breast-feeding was negatively (though non-significantly) associated with growth. Sanitation facilities and breast-feeding are, however, important determinants during the first year of life. Among children over 1 year of age, socioeconomic variables and gender are the most important predictors. Breast-feeding is shown to provide more important health benefits for children in lower income households. The need for further studies on the causes of gender differences in nutritional status was apparent. PMID- 8478370 TI - Gender of children and contraceptive use. AB - In 1984, half of married/cohabiting Canadian women aged 18-49 years were using contraception, with sterilisation being the most prevalent method. This study, using data from the 1984 Canadian Fertility Survey of 5315 women aged 18-49 years, found that there was a preference for sons. Women with two sons are more likely to use contraception than those who have had two daughters; the gender of children may have a weak effect on contraceptive behaviour of Canadian couples at higher parities. Sociocultural factors (e.g. education, religion, religiosity) were also found to influence contraceptive behaviour. PMID- 8478371 TI - Factors responsible for childhood mortality variation in rural Ethiopia. AB - This paper uses the 1981 National Rural Demographic Survey to document childhood mortality variations in rural areas of Ethiopia. Four significant findings are highlighted. (1) Health status of parents is identified as an important determinant of childhood mortality. (2) Religion, region of residence and ethnicity interact in their effects on childhood mortality and the effect of ethnicity varies in different regions for the same religion; in some areas ethnicity may serve as a proxy for economic and cultural differences. (3) Childhood mortality is inversely related to literacy status of parents, which may also reflect socioeconomic status. (4) The data show a clear difference in childhood mortality between the famine-prone areas and the rest. PMID- 8478372 TI - Diffusion of a particular 4.1(-) hereditary elliptocytosis allele in the French Northern Alps. AB - Heterozygous 4.1(-) hereditary elliptocytosis results from the absence of one haploid set of protein 4.1, a major component of the red cell skeleton. Two successive epidemiological investigations revealed fifteen probands in the French Northern Alps. The frequency of this disease seems to be very high in four small villages isolated in the Aravis mountains. The genealogical study shows that eleven probands share common ancestors who lived eight or ten generations ago in these villages. Thus there was probably a founder effect from one pair of ancestors, strengthened by endogamy. In contrast, four probands originate from another area and are not genealogically related. Recent results in molecular genetics support the present data. PMID- 8478373 TI - Evaluation of natural family planning programmes in Liberia and Zambia. AB - Studies to evaluate use-effectiveness and cost-effectiveness of natural family planning (NFP) were conducted in Liberia and Zambia. The Liberian programme provided uni-purpose NFP services to 1055 clients mainly in rural areas; the Zambian programme provided NFP services integrated with MCH to 2709 clients predominantly in urban areas. The one-year life table continuation and unplanned pregnancy rates were 78.9 and 4.3 per 100 woman-years in Liberia, compared to 71.2 and 8.9 in Zambia. However, high rates of loss to follow-up mandate caution in interpretation of these results, especially in Zambia. More women progressed to autonomous NFP use in Liberia (58%) than in Zambia (35.3%). However, programme costs per couple-year protection were lower in Zambia (US$25.7) than in Liberia (US$47.1). Costs per couple-year protection were higher during learning than autonomy, and declined over time. These studies suggest that NFP programmes can achieve acceptable use- and cost-effectiveness in Africa. PMID- 8478374 TI - Family background, cognitive abilities, and personality as predictors of education and occupational attainment across two generations. AB - This study reports on the relative influences of parental attainment and cognitive ability and subjects' own cognitive ability, personality, and social attitudes on the educational and occupational attainments and incomes of 183 Generation 3 subjects of Caucasian ancestry and 186 of Japanese ancestry originally tested in 1972-76 in the Hawaii Family Study of Cognition (HFSC) and re-tested in 1987-88. In contrast to earlier reports of sex differences in the influence of Generation 2 attainment and on Generation 3 attainment when these offspring were younger, family background had a trivial influence and own cognitive ability had a substantial influence on educational attainment for both racial/ethnic groups and both sexes. For income, however, own cognitive ability was only a significant predictor for male subjects. Within-family correlational analyses also supported this sex difference in influences on attainment. PMID- 8478375 TI - Open reduction and internal fixation of displaced intra-articular fractures of the glenoid fossa. AB - Ten displaced intra-articular fractures of the glenoid fossa were treated with open reduction and internal fixation between 1980 and 1987. Nine patients were available for evaluation at an average of four years (range, two to ten years) after the operation. Eight patients had mild or no symptoms and little or no restriction of the motion of the shoulder. There were no infections or malunions. The only complication was heterotopic ossification in one patient. Radiographic evaluation showed no evidence of traumatic osteoarthrosis in any patient. Open reduction and internal fixation is a useful and safe technique for the treatment of selected, displaced fractures of the glenoid fossa, and it can restore excellent function of the shoulder. PMID- 8478376 TI - Prosthetic replacement of the shoulder for the treatment of defects in the rotator cuff and the surface of the glenohumeral joint. AB - We operatively treated, between 1978 and 1987, twenty-one shoulders in nineteen patients, fifty-four to eighty-four years old, who had disabling pain attributable to a massive tear of the rotator cuff, accompanied by loss of the surface of the glenohumeral joint. These patients were not candidates for total shoulder replacement because of the massive deficiency in the cuff and the fixed upward displacement of the humeral head. A prerequisite for hemiarthroplasty was a functionally intact coracoacromial arch to provide superior secondary stability for the prosthesis. One important aspect of the operative technique was the selection of a sufficiently small prosthesis so that excessive tightness of the posterior aspect of the capsule could be avoided. Eighteen shoulders in sixteen patients were available for follow-up, which ranged from twenty-five to 122 months. Pain decreased from marked or disabling in fourteen shoulders preoperatively to none or slight in ten and to pain only after unusual activity in four. Active forward elevation improved from an average of 66 degrees preoperatively to an average of 109 degrees postoperatively. One patient, who had had an excellent result, fell and sustained an acromial fracture, so the functional result changed to poor. Three patients had persistent, substantial pain in the shoulder that led to a revision. Neither infection nor prosthetic loosening developed in any shoulder. PMID- 8478377 TI - Instability of the shoulder after arthroplasty. AB - A replacement arthroplasty was performed in 236 shoulders at The Hospital for Special Surgery from 1984 through 1989. Ten patients (eight women and two men) from that group were identified as having instability of the shoulder at the time of follow-up, and the results for these patients were reviewed retrospectively. The ages of the patients ranged from fifty-six to seventy-nine years. The instability was anterior in seven of the patients and posterior in three. The anterior instability was caused by a rupture of the repaired subscapularis tendon. The operative treatment of the anterior instability consisted of mobilization and repair of the tendon, but three of the seven patients continued to have instability. A static stabilizer, consisting of an allograft of Achilles tendon, was inserted in these three patients, and the result was a success. The etiology of the posterior instability (three patients) was multifactorial. Treatment consisted of correction of any soft-tissue imbalance and revision of the prosthetic components as necessary. All ten patients were followed clinically and radiographically for at least two years. All of the patients had some loss of motion of the shoulder as compared with the motion before the dislocation. There were no neurovascular complications, problems related to the allografts, or any other complications. We concluded that proper balancing of the soft tissues and positioning of the prosthetic components are essential to a successful arthroplasty of the shoulder. The postoperative rehabilitation should include a physical therapy program in which the range of motion of the arm that was achieved in the operating room is not exceeded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478378 TI - Capitellocondylar total elbow replacement in rheumatoid arthritis. Long-term results. AB - We evaluated the long-term results of 202 capitellocondylar total elbow replacements that had been performed, from July 1974 through June 1987, in 172 patients. The duration of follow-up averaged sixty-nine months (range, twenty four to 178 months). At the most recent follow-up examination, use of a 100-point rating score demonstrated an improvement from an average preoperative score of 26 points (range, 2 to 50 points) to an average postoperative score of 91 points (range, 45 to 100 points). The most improvement occurred in the categories of relief of pain, functional status, and range of motion in all planes except extension. The improvements in these categories and in the roentgenographic appearance that were seen in the early postoperative period did not deteriorate with time. The average preoperative arc of motion at the elbow ranged from -37 degrees of extension to 118 degrees of flexion. The average postoperative arc of motion at the elbow ranged from -30 degrees of extension to 135 degrees of flexion. Supination improved from 45 degrees preoperatively to 64 degrees postoperatively; pronation improved from 56 degrees preoperatively to 72 degrees postoperatively. The roentgenograms showed a radiolucent line adjacent to eight humeral and nineteen ulnar components; most of the lines were incomplete and one millimeter wide or less. Revision of the prosthesis was necessary in three elbows (1.5 per cent) because of loosening without infection, and in three additional elbows because of dislocation of the prosthesis. Complications included deep infection in three elbows (1.5 per cent); problems related to the wound in fifteen (7 per cent); permanent, partial sensory ulnar-nerve palsy in five (2.5 per cent); permanent, partial motor ulnar-nerve palsy in one (0.5 per cent); and dislocation in seven (3.5 per cent). PMID- 8478379 TI - The function of the quadriceps muscle after a fracture of the femur in patients who are less than seventeen years old. AB - Thirty-three patients who had been managed for an isolated, closed fracture of the femoral shaft when they were less than seventeen years old were examined at an average of thirty-three months (range, eighteen to fifty-six months) after the injury. Thirteen patients (39 per cent) had a persistent deficit in the strength of the quadriceps of the fractured limb, as identified on testing with a Cybex-II isokinetic dynamometer. Six patients (18 per cent) had a deficit according to the one-leg-hop for distance test, fourteen (42 per cent) had an average loss of ten millimeters in the circumference of the thigh, and sixteen (48 per cent) had an average loss of 10 degrees of flexion of the knee. The etiological factors that were thought to possibly be responsible for the weakness of the quadriceps were evaluated. The amount of maximum displacement of the fracture, as seen on the initial radiographs, was the only factor that was significant for the prediction of weakness of the quadriceps (p = 0.006) at both test speeds of the Cybex dynamometer and in all statistical analyses. Despite the persistent weakness of the quadriceps, none of the patients had a clinical problem at the latest follow up examination. A subclinical deficit in the strength of the quadriceps may be related to damage sustained by the muscle at the time of the fracture. On the basis of the results of this study, we do not recommend a change from the traditional methods of treatment, which involve early application of a spica cast or use of traction followed by application of a spica cast. PMID- 8478380 TI - Scoliosis in children after thoracotomy for aortic coarctation. AB - A follow-up study was performed to assess the prevalence of scoliosis in 160 patients in whom aortic coarctation had been treated operatively through a left posterolateral incision in the fourth intercostal space. Scoliosis had not been seen in any patient before the thoracotomy, but a scoliosis of 10 degrees or more was observed in thirty-five patients (22 per cent) at the follow-up examination, which was performed an average of seven years after the thoracotomy. The scoliosis was a thoracic curve and was directed to the left in twenty-six of the thirty-five patients. Most of the curves were mild (between 10 and 20 degrees) and hardly progressed during the follow-up period. The high-risk period for the onset of scoliosis began about three years after the operation. The prevalence of scoliosis did not correlate significantly with the age or sex of the patients. PMID- 8478381 TI - The use of one compared with two distal screws in the treatment of femoral shaft fractures with interlocking intramedullary nailing. A clinical and biomechanical analysis. AB - The torsional and compressive biomechanical characteristics of a system for intramedullary fixation with a slotted locking nail and either one or two distal locking screws were evaluated in sixteen femora obtained from eight cadavera. No significant difference was found in the torsional rigidity or axial load to failure when one as opposed to two distal screws had been used. We also managed twenty-seven patients who had a fracture of the femoral shaft with interlocking fixation, using only a single distal screw for distal fixation. The average duration of follow-up was nine months (range, three to twenty-five months). The average time to radiographic healing was three months (range, two to six and one half months). There were no non-unions or failures of the implant. Clinically unimportant migration of the distal screw occurred in five patients. We concluded that one distal screw provides adequate distal fixation of fractures of the femoral shaft treated with interlocking intramedullary nailing. PMID- 8478382 TI - Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. AB - The origin and differentiation of cells in the repair of three-millimeter diameter, cylindrical, full-thickness drilled defects of articular cartilage were studied histologically in New Zealand White rabbits. The animals were allowed to move freely after the operation. Three hundred and sixty-four individual defects from 122 animals were examined as long as forty-eight weeks postoperatively. In the first few days, fibrinous arcades were established across the defect, from surface edge to surface edge, and this served to orient mesenchymal cell ingrowth along the long axes. The first evidence of synthesis of a cartilage extracellular matrix, as defined by safranin-O staining, appeared at ten days. At two weeks, cartilage was present immediately beneath the surface of collagenous tissue that was rich in flattened fibrocartilaginous cells in virtually all specimens. At three weeks, the sites of almost all of the defects had a well demarcated layer of cartilage containing chondrocytes. An essentially complete repopulation of the defects occurred at six, eight, ten, and twelve weeks, with progressive differentiation of cells to chondroblasts, chondrocytes, and osteoblasts and synthesis of cartilage and bone matrices in their appropriate locations. At twenty-four weeks, both the tidemark and the compact lamellar subchondral bone plate had been re-established. The cancellous woven bone that had formed initially in the depths of the defect was replaced by lamellar, coarse cancellous bone. Autoradiography after labeling with 3H-thymidine and 3H-cytidine demonstrated that chondrocytes from the residual adjacent articular cartilage did not participate in the repopulation of the defect. The repair was mediated wholly by the proliferation and differentiation of mesenchymal cells of the marrow. Intra-articular injections of 3H-thymidine seven days after the operation clearly labeled this mesenchymal cell pool. The label, initially taken up by undifferentiated mesenchymal cells, progressively appeared in fibroblasts, osteoblasts, articular chondroblasts, and chondrocytes, indicating their origin from the primitive mesenchymal cells of the marrow. Early traces of degeneration of the cartilage matrix were seen in many defects at twelve to twenty weeks, with the prevalence and intensity of the degeneration increasing at twenty-four, thirty-six, and forty-eight weeks. Polarized light microscopy demonstrated failure of the newly synthesized repair matrix to become adherent to, and integrated with, the cartilage immediately adjacent to the drill-hole, even when light microscopy had shown apparent continuity of the tissue. In many instances, a clear gap was seen between repair and residual cartilage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478383 TI - Primary total hip reconstruction with a titanium fiber-coated prosthesis inserted without cement. AB - A prospective study was done of the intermediate-term clinical and radiographic results of 121 total hip arthroplasties in which a Harris-Galante porous titanium fiber-coated prosthesis was inserted without cement in 110 patients. The average age at the time of the operation was forty-nine years (range, twenty to seventy years). The average duration of follow-up was sixty-seven months (range, fifty five to seventy-nine months). The average preoperative Harris hip score was 55 points, and the average postoperative score was 93 points. One acetabular component was revised due to recurrent dislocation. Eleven femoral implants were unstable, and of these, four were revised. Cortical erosion was present around the distal part of the femoral stem in nine patients (8 per cent) who had stable implants, and one of these femoral implants was revised because the erosion was extensive. Survivorship analysis at five years revealed a 97 per cent chance of survival (95 per cent confidence limit, 0.937 to 1.0) of the Harris-Galante femoral-stem implant inserted without cement. PMID- 8478384 TI - Hip and knee replacement in osteogenesis imperfecta. AB - Five total hip and three total knee arthroplasties were performed, from 1969 to 1990, in six patients who had osteogenesis imperfecta. The patients who had a hip arthroplasty were followed for a mean of seven years, and those who had a knee arthroplasty, for a mean of ten years. Postoperatively, all had relief of pain and were able to walk; one patient used a walker and two used a cane. The only postoperative complication was an intrapelvic protrusion of the acetabular component six years after a bipolar hip replacement. PMID- 8478385 TI - Pulmonary function during and after total hip replacement. Findings in patients who have insertion of a femoral component with and without cement. AB - Eleven patients who had a femoral component inserted with cement and twenty-three who had a femoral component inserted without cement were studied prospectively for changes in the pulmonary shunt associated with total hip replacement. The levels of oxygen in the arterial blood and the platelet counts were measured preoperatively and each morning for three days after the arthroplasty. Levels of oxygen in the arterial blood were determined intraoperatively, once before and once after the femoral component was inserted. Intraoperative shunt values increased 28 per cent when a femoral component was inserted with cement (p < 0.05), but they did not change when cement was not used. The average postoperative shunt values were higher than the average preoperative shunt values for both groups of patients, but only the values on the second postoperative day after a procedure with cement were significantly higher (p < 0.05). The ability of the patient to tolerate an increase in pulmonary shunt should be assessed when the femoral component is to be cemented during total hip replacement. PMID- 8478386 TI - Pyomyositis in patients who have the human immunodeficiency virus. Case report and review of the literature. PMID- 8478387 TI - Anterior dislocation of the distal end of the ulna after use of a compression plate for the treatment of a Galeazzi fracture. A case report. PMID- 8478388 TI - A unique multifocal osteoblastoma-like tumor of the bones of a single lower extremity. Report of a case. PMID- 8478389 TI - Sciatica caused by a neurilemoma of the intrapelvic portion of the sciatic nerve. A case report. PMID- 8478390 TI - Cytogenetic and molecular cytogenetic techniques in orthopaedic surgery. PMID- 8478391 TI - Biopsy of bone and soft-tissue lesions. PMID- 8478392 TI - Diagnostic strategy for bone and soft-tissue tumors. AB - The diagnostic strategy to be used for a bone tumor depends on the ability of the clinician to make an accurate differential diagnosis on the basis of clinical information and plain radiographs. The clinician must be able to classify the patient as having a non-progressive or a progressive primary benign bone tumor, a primary malignant bone tumor, or a metastatic bone tumor. Only after assignment to one of these four categories can an effective diagnostic strategy ensue. If the clinical and radiographic information favors a diagnosis of malignant or aggressive benign bone tumor, the clinician should refer the patient to an experienced orthopaedic oncologist without performing additional diagnostic tests or a biopsy. If a soft-tissue mass is five centimeters in diameter or larger on physical examination, and especially if it is deep to the fascia, the patient should also be referred to an orthopaedic oncologist, without additional evaluation or biopsy, because of the relatively high probability that the mass is malignant. PMID- 8478393 TI - Early and late loosening of the acetabular cup after low friction arthroplasty. PMID- 8478394 TI - Early and late loosening of the acetabular cup after low-friction arthroplasty. PMID- 8478395 TI - Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. AB - We measured, in vivo, the local concentration of nitric oxide (NO) in cerebral tissue, during and after transient middle cerebral artery occlusion in the rat (n = 8). Baseline concentration of NO was < 10(-8) M; upon initiation of ischemia, NO concentration increased to approximately 10(-6) M and then declined. Reperfusion likewise stimulated an increase in NO concentration to above baseline level. Administration of N-nitro-L-arginine methyl ester (n = 4), an inhibitor of nitric oxide synthase, before onset of ischemia, maintained NO at basal levels. Our data indicate that large increases in NO occur at onset of ischemia, which may affect tissue response to an ischemic insult. PMID- 8478396 TI - Basic FGF, NGF, and IGFs protect hippocampal and cortical neurons against iron induced degeneration. AB - Iron is believed to contribute to the process of cell damage and death resulting from ischemic and traumatic insults by catalyzing the oxidation of protein and lipids. Exposure of cultured rat hippocampal neurons to iron (FeSO4) caused a dose-dependent reduction in neuronal survival, which was potentiated by ascorbate. Damage to neurons was associated with a significant level of oxygen radical in the culture medium. The iron chelator desferal prevented both the neuronal degeneration caused by FeSO4 and the production of oxygen radical, demonstrating that ionic iron was responsible for the cell damage. Iron neurotoxicity was associated with an elevation of [Ca2+]i and was attenuated by NMDA receptor antagonists. Since recent findings demonstrated neuroprotective effects of growth factors in cell culture and in vivo models of ischemia, we examined the effects of growth factors on iron-induced damage. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage. Both rat hippocampal and human cortical neurons were protected by these growth factors. Taken together, the data suggest that the neuroprotective effects of growth factors against excitotoxic/ischemic insults may result, in part, from a prevention or attenuation of oxidative damage. PMID- 8478397 TI - Temperature modulation of cerebral depolarization during focal cerebral ischemia in rats: correlation with ischemic injury. AB - The role of cerebral depolarizations in focal cerebral ischemia is unknown. We therefore measured the direct current (DC) electrical activity in the cortex of Wistar rats subjected to transient occlusion of the middle cerebral artery (MCA). Focal ischemia was induced for 90 min by insertion of an intraluminal filament to occlude the MCA. To modulate cell damage, we subjected the rats to hypothermic (30 degrees C, n = 4), normothermic (37 degrees C, n = 4), and hyperthermic (40 degrees C, n = 6) ischemia. Controlled temperatures were also maintained during 1 h of reperfusion. Continuous cortical DC potential changes were measured using two active Ag-AgCl electrodes placed in the cortical lesion. Animals were killed 1 week after ischemia. The brains were sectioned and stained with hematoxylin and eosin, for evaluation of neuronal damage, and calculation of infarct volume. All animals exhibited an initial depolarization within 30 min of ischemia, followed by a single depolarization event in hypothermic animals, and multiple periodic depolarization events in both normothermic and hyperthermic animals. Hyperthermic animals exhibited significantly more (p < 0.05) DC potential deflections (n = 6.17 +/- 0.67) than normothermic animals (n = 2.75 +/- 0.96). The ischemic infarct volume (% of hemisphere) was significantly different for the various groups; hypothermic animals exhibited no measurable infarct volume, while the ischemic infarct volume was 10.2 +/- 12.3% in normothermic animals and 36.5 +/- 3.4% in hyperthermic animals (p < 0.05). A significant correlation was detected between the volume of infarct and number of depolarization events (r = 0.90, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478398 TI - Thermal sensitivity of hypoxic responses in neocortical brain slices. AB - Electrophysiological responses to transient hypoxia were studied in neocortical brain slices from adult gerbils. Evoked responses and direct current (DC) potentials were recorded in layer III of the parietal cortex under normoxic and hypoxic conditions. The excitatory synaptic component of the evoked waveform was identified by its sensitivity to calcium and 6,7-dinitroquinoxaline-2,3-dione (DNQX). Under normoxic conditions, hypothermia reduced excitatory synaptic responses in a temperature-dependent manner. Under hypoxic conditions, hypothermia prolonged the delays to synaptic loss and hypoxic depolarization in a temperature-dependent manner. Synaptic recovery following a fixed period under hypoxic depolarization was greatly enhanced when hypoxia was administered at reduced temperature. The findings demonstrate that evoked responses are reduced under hypothermic conditions, but that these responses are sustained for a longer period of time during hypoxia. The data suggest that hypothermia protects against hypoxic damage to excitatory synaptic mechanisms in the neocortex both by prolonging the delay to hypoxic depolarization, and by extending the period of hypoxic depolarization that can be tolerated. PMID- 8478399 TI - Alterations in protein kinase C activity and membrane lipid metabolism in cerebral vasospasm after subarachnoid hemorrhage. AB - Changes in protein kinase C (PKC) activity, membrane lipid metabolism, and the extent of 20-kDa myosin light chain (MLC) phosphorylation in spastic cerebral basilar arteries were examined by using the beagle "two-hemorrhage" model of subarachnoid hemorrhage. In spastic arteries at days 4 and 7, cytosolic PKC activity showed a decrease of 40-45% with no significant changes in membrane PKC activity as compared with nonspastic control arteries. Cytosolic PKC activity of the day 14 arteries returned toward the normal control level with the remission of vasospasm. Western blot analysis of the PKC isoforms revealed that the amounts of PKC alpha and PKC epsilon but not PKC zeta were decreased in spastic arteries. As compared with nonspastic arteries, spastic arteries showed higher rates of incorporation of [3H]choline into phosphatidylcholine (PC) and [14C]ethanolamine into phosphatidylethanolamine (PE), but not of [3H]myoinositol into phosphoinositides, suggesting the stimulated turn-over of PC and PE. The extent of 20-kDa MLC phosphorylation was not increased in the spastic arteries at days 4 or 7 as compared with that in the nonspastic control arteries. These results demonstrate that PKC activity and related membrane lipid metabolism are altered in spastic basilar arteries after subarachnoid hemorrhage. PMID- 8478400 TI - PET study of changes in local brain hemodynamics and oxygen metabolism after unilateral middle cerebral artery occlusion in baboons. AB - Local cerebral hemodynamics and oxygen metabolism were measured by positron emission tomography (PET) with the oxygen-15 (15O) steady-state method in baboons, immediately before (T0), 1 (T1), and 3-4 (T2) h after permanent middle cerebral artery occlusion (MCAO). At T1, there was a marked fall in both cerebral blood flow (CBF) and the CBF/cerebral blood volume (CBV) ratio in the occluded territory; these changes were sustained at T2, indicating stable reduction in cerebral perfusion pressure and lack of spontaneous reperfusion within this time range. Compared with preocclusion conditions, the oxygen extraction fraction (OEF) in the occluded territory was elevated at both T1 and T2, indicative of a persistent oligemia/ischemia for up to 3 h after MCAO. At T2, however, this OEF increase had lessened, concomitantly with a decline in cerebral metabolic rate of oxygen (CMRO2). This impairment of oxidative metabolism occurred earlier in the deep, compared with the cortical, MCA territories; in the latter, the CMRO2 was essentially preserved at T1 and only moderately reduced at T2, possibly suggesting prolonged viability. Finally, no significant changes in CBF or CMRO2 were observed in the contralateral MCA territory in this time range after MCAO. Despite methodological limitations (mainly partial volume effects related to PET imaging, which may have resulted in an underestimation of true changes and an overlooking of heterogeneous changes) our study demonstrates the feasibility of the combined PET-MCAO paradigm in baboons; this experimental approach should be valuable in investigating the pathophysiology and therapy of acute stroke. PMID- 8478401 TI - Analysis of individual positron emission tomography activation maps by detection of high signal-to-noise-ratio pixel clusters. AB - We present a new method for the analysis of individual brain positron emission tomography (PET) activation maps that looks for activated areas of a certain size rather than pixels with maximum values. High signal-to-noise-ratio pixel clusters (HSC) are identified and their sizes are statistically tested with respect to a Monte-Carlo-derived distribution of cluster sizes in pure noise images. From multiple HSC size tests, a strategy is proposed for control of the overall type I error. The sensitivity and specificity of this method have been assessed using realistic Monte Carlo simulations of brain activation maps. When compared with the gamma 2 statistic of the local maxima distribution, the proposed method showed enhanced sensitivity, particularly for signals of low magnitude and/or large size. Its potential for the individual analysis of PET activation studies is presented in two sets of subjects who underwent two cognitive protocols. Although it can be viewed as an alternative to the classical stereotactic averaging approach, this new method is intended to be a first step toward the analysis of single-subject PET activation studies. PMID- 8478402 TI - Early detection of Alzheimer's disease: a statistical approach using positron emission tomographic data. AB - Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD. PMID- 8478403 TI - Reliability of regional cerebral blood flow activation to cognitive tasks in elderly normal subjects. AB - The assessment of cerebral blood flow (CBF) using noninvasive 133Xe techniques provides an indirect measurement of cortical metabolic activity. The utility of this method in longitudinal clinical studies depends on the stability and reproducibility of resting and activated flow measures. We evaluated CBF in a sample of 16 elderly normal subjects (aged 54-73 years) at rest and during task performance in two sessions separated by an average of 9 weeks. Resting global CBF was lower in the second session, a finding consistent with the known effects of habituation previously reported. Regionally specific activated CBF did not change with repeated measurements. The results provide evidence that the 133Xe technique is reliable and of potential utility in evaluating the effect of the natural course of brain disease, as well as the effects of therapeutic interventions on brain activity. PMID- 8478404 TI - Modeling analysis of [11C]flumazenil kinetics studied by PET: application to a critical study of the equilibrium approaches. AB - The multi-injection modeling approach was used for the in vivo quantitation of benzodiazepine receptors in baboon brain using positron emission tomography (PET) and [11C]flumazenil (RO 15-1788) as a specific ligand. The model included three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The plasma concentration after correction for the metabolites was used as the input function. The experimental protocol consisted of four injections of labeled and/or unlabeled ligand. This protocol allows the evaluation, from a single experiment, of the five model parameters in various regions of interest. For example, in the temporal cortex, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (Kd) were estimated to be 70 +/- 15 pmol/ml and 15.8 +/- 2.2 nM, respectively. The validity of the equilibrium approach, which is the most often used quantitation method, has been studied from simulated data calculated using these model parameters. The equilibrium approaches consist of reproducing in PET studies the experimental conditions that permit the use of the usual in vitro methods such as Scatchard analysis. These approaches are often open to criticism because of the difficulty of defining the notion of equilibrium in in vivo studies. However, it appears that the basic relation of Scatchard analysis is valid over a broader range of conditions than those normally used, such as the requirement of a constant bound/free ratio. Simulations showed that the values of the receptor concentration (B'max) and the equilibrium dissociation constant (Kd) found using Scatchard analysis are always underestimated. These simulations also suggest an explanation concerning the dependency of B'max and Kd on the time point employed for the Scatchard analysis, a phenomenon found by several authors. To conclude, we propose new protocols that allow the estimation of the B'max and Kd parameters using a Scatchard analysis but based on a protocol including only one or two injections. These protocols being entirely noninvasive, it thus becomes possible to investigate possible changes in receptor density and/or affinity in patients. PMID- 8478405 TI - Defective brain energy metabolism shown by in vivo 31P MR spectroscopy in 28 patients with mitochondrial cytopathies. AB - We studied brain energy metabolism by phosphorus magnetic resonance spectroscopy (31P MRS) in 28 patients with mitochondrial cytopathies, and 20 normal control subjects. Fourteen patients had myopathy alone, six had only mild brain symptoms, and eight showed different degrees of brain involvement. Brain 31P MRS showed a low phosphocreatine content in all patients, accompanied by a high inorganic phosphate in 14 of 28 patients. The average value of the Pi concentration in the patient group was significantly (p = 0.009) different from the control group. The cytosolic pH was normal. From these data were derived a high concentration of ADP (calculated from the creatine kinase equilibrium), a high percent value of V/Vmax for ATP biosynthesis, and a low phosphorylation potential, all features showing a derangement of brain energy metabolism, in all patients with mitochondrial cytopathies. 31P MRS proved to be sensitive enough to disclose a deficit of mitochondrial functionality not only in the affected patients, but also in those without clinically evident brain symptoms. PMID- 8478406 TI - Hypoxia increases velocity of blood flow through parenchymal microvascular systems in rat brain. AB - The postulation that hypoxia increases local cerebral blood flow (lCBF) mainly by perfusing more capillaries (the capillary recruitment hypothesis) was tested in awake adult male Sprague-Dawley rats exposed to 10% O2 and control rats. The [14C]iodoantipyrine technique was used to measure lCBF. Local cerebral blood volume was determined by measuring plasma and red cell distribution spaces within the brain parenchyma with 125I-labeled serum albumin (RISA) and 55Fe-labeled red cells (RBC), respectively. Tissue radioactivity in 44 brain areas was estimated by quantitative autoradiography. Hypoxia raised lCBF by 25-90% in all brain areas. In about one-quarter of the brain areas, the rise in blood flow was associated with a small increase in microvascular plasma and blood volumes. This change in blood volume, which could be the result of perfusing more parenchymal microvessels and/or increasing parenchymal microvessel diameter, is not sufficient to account for the observed rise in lCBF. In the remaining areas the RISA, RBC, and blood spaces were either unchanged or only marginally increased by hypoxia. For this hypoxic perturbation, the major mechanism of raising blood flow appears to be increased velocity of microvessel perfusion and not perfusion of more capillaries. These findings provide only limited support for the capillary recruitment hypothesis. PMID- 8478407 TI - The velocities of red cell and plasma flows through parenchymal microvessels of rat brain are decreased by pentobarbital. AB - Local cerebral blood flow is lowered in many brain areas of the rat by high-dose pentobarbital (50 mg/kg). In the present study, the mechanism of this flow change was examined by measuring the distribution of radiolabeled red blood cells (RBCs) and albumin (RISA) in small parenchymal microvessels and calculating the microvascular distribution spaces and mean transit times of RBCs, RISA, and blood. In most brain areas, pentobarbital slightly decreased the RISA space, modestly increased the RBC space, and did not alter the blood space. The mean transit times of RBCs, RISA, and blood through the perfused microvessels were considerably greater in treated rats than in controls. These findings indicate that the mechanism by which high-dose pentobarbital diminishes local cerebral blood flow in rat brain is, in the main, a lowered linear velocity of plasma and RBC flow through small parenchymal microvessels and not decreased percentage of perfused capillaries (capillary retirement). This response is probably driven mainly by lowered local metabolism and may well entail a slight increase in the number of small microvessels that are perfused by RBCs. PMID- 8478408 TI - Electrical and mechanical changes during anoxic contractions of the isolated canine basilar artery. AB - Isometric tension and membrane potential were measured to determine the electrophysiological events occurring during anoxia in the isolated canine basilar artery. Anoxia induced transient contractions which were inhibited by the Ca(2+)-channel inhibitor, diltiazem, and were abolished in Ca(2+)-free solution. Anoxic contractions were accompanied by membrane depolarizations, which were resistant to diltiazem. When matched contractions were obtained with anoxia and high K+, the level of membrane depolarization was smaller during anoxic contractions. These results support the importance of voltage-dependent Ca2+ influx in the generation of anoxic contractions in the canine basilar artery. However, membrane depolarization does not fully account for these anoxic contractions. PMID- 8478409 TI - Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy. AB - Near-infrared spectroscopy (NIRS) was used to monitor human visual cortical function during and after photic stimulation (PS) in five adult volunteers. Cerebral blood volume (CBV) increased on the occipital surface during PS, but NIRS parameters did not change on the frontal surface. The increase in CBV was caused by a rapid increase in oxyhemoglobin with but a small increase in deoxyhemoglobin, suggesting cerebral vascular dilatation with decreased oxygen consumption. After PS stopped, CBV promptly decreased and then slightly increased again. Cytochrome aa3 did not show any change during and after PS. These phenomena reappeared following repeated PS in all five subjects. These results may represent the first step in the development of NIRS imaging. PMID- 8478410 TI - Effect of propentofylline on regional cerebral glucose metabolism in acute ischemic stroke. AB - In a randomized double-blind placebo-controlled study in 30 patients with acute ischemic stroke, the effect of the adenosine uptake blocker propentofylline on regional brain glucose metabolism (rCMRglu) was investigated using repeated positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Treatment was initiated within 48 h after onset of symptoms. The clinical course was followed for 3 months. In the propentofylline group, after 14 days rCMRglu was increased in the infarct by 37.3% and was practically unchanged in other brain regions, whereas in the control group glucose metabolism had decreased in all regions (1.4-13.4%). These differences were significant between the two groups [Analysis of variance (ANOVA) p = 0.005]. Although there was a trend toward greater clinical improvement in the propentofylline-treated patients, this did not reach statistical significance. The results correspond to experimental data showing that propentofylline improves energy metabolism in cerebral ischemia. A clinical trial is needed to determine whether this new therapeutic principle can be successfully used in acute human stroke. PMID- 8478411 TI - Local cerebral blood flow in rats with congenital hydrocephalus. AB - Local cerebral blood flow (LCBF) has been measured by [14C]iodoantipyrine quantitative autoradiography in H-Tx rats with inherited congenital hydrocephalus at 10, 21, and 30 days after birth. LCBF at 10 days was uniformly low in all ten brain regions studied and not significantly different between hydrocephalic and age-matched control rats. By 21 days LCBF had increased significantly in control rats. LCBF was significantly lower (< 69%) in the hydrocephalics in all cortical regions and in the inferior colliculus LCBF at both 21 and 30 days. The cerebellar cortex, pons, and caudate were not significantly affected. At 30 days LCBF ranged from 55 to 115 ml 100 g-1 min-1 for hydrocephalics and from 100 to 183 ml 100 g-1 min-1 for controls. PMID- 8478412 TI - Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis. AB - We tested the hypothesis that the CBF response to extracellular acidosis is mediated by nitric oxide (NO). A closed cranial window, superfused with artificial CSF (aCSF), was implanted over the parietal cortex in anesthetized and ventilated Wistar rats. Regional cerebral blood flow (rCBF) was measured continuously with laser-Doppler flowmetry (LDF). The reaction of rCBF to hypercapnia (PaCO2 from 30.5 +/- 1.8 to 61.3 +/- 5.8 mm Hg by adding CO2 to the inspiratory gas) was 2.9 +/- 1.4%/mm Hg, and the reaction of rCBF to H+ (superfusion of acidic aCSF, pH 7.07 +/- 0.05) was 101.7 +/- 24.7%/pH unit. The regional NO synthase (NOS) activity was blocked by superfusing aCSF containing 10(-3) M N omega-nitro-L-arginine (L-NA, n = 10). After 30 min of L-NA superfusion, rCBF was reduced to 80.1 +/- 6.5% of baseline, and the rCBF responses to hypercapnia (PaCO2 from 30.9 +/- 2.9 to 58.8 +/- 7.7 mm Hg) and extracellular acidosis (aCSF pH 7.08 +/- 0.06) were reduced to 0.8 +/- 1.1%/mm Hg and 10.1 +/- 23.0%/pH unit, respectively (both p < 0.001). This effect was stereospecific since aCSF containing 10(-3) M N omega-nitro-D-arginine affected neither baseline rCBF nor the response to H+ (n = 5). The NOS blockade did not affect the vasodilatation by the NO donor sodium nitroprusside (n = 5, 114.3 +/- 25.1% before vs. 130.2 +/- 24.7% after NOS blockade). The results confirm the involvement of NO in the CBF reaction to hypercapnia and demonstrate for the first time that NOS blockade also strongly attenuates the H+ response of the cerebral vasculature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478413 TI - Cumulative author, subject, compound and special issue indexes. Volumes 551-600 (1991-1992). PMID- 8478414 TI - A region of the mouse genome homologous to human chromosome 1q21 affects facial clefting. AB - We sought to determine whether mouse chromosomal regions homologous to human chromosomal regions implicated in the etiology of facial clefting would be related to the incidence of spontaneous cleft palate (CP) or cleft lip with or without cleft palate [CL(P)], Dilantin-induced CL(P), hydrocortisone-induced CP, and/or 6-aminonicotinamide-induced CP. We found that a region on mouse chromosome 3, homologous to human chromosome 1q21, significantly increased the incidence of sporadic CL(P) when the allele from the A/J inbred strain was present. None of the other chromosomal regions or conditions studied had significant associations with this susceptibility to facial clefting, although there was a suggestion that the B allele of the same region was associated with hydrocortisone-induced CP. Thus, the region on human chromosome 1q21 should be further studied for a role in the etiology of human CL(P). PMID- 8478415 TI - Changes in human palatine bone location and tongue position during prenatal palatal closure. AB - Closure of the palatal shelves during normal prenatal palate formation is commonly supposed to be the result of a complex interaction between tissue growth processes and functional factors such as mandibular and tongue movements. The purpose of the present study was to analyze tongue and palatine bone positions during palatal shelf closure. The material consisted of 40 normal human fetuses (CRL 26-57 mm). The series covers the developmental stages in which palatal shelf closure takes place. The spatial relation between the tip of the tongue and the lips was examined by visual inspection, and radiographic/cephalometric methods were used for analyzing palatine bone positions. On axial radiographs of the upper jaws, the angle in the horizontal plane between the vertical plates of the palatine bones was measured. The study revealed that the vertical plates of the palatine bones rotate on their vertical axes during palatal closure, the mean interpalatine angle changing from 23.7 degrees (SD 2.0 degrees) to 13.3 degrees (SD 3.2 degrees), P < 0.001. The rotation of the palatine bones occurred while the cranial base was still unossified. Moreover, the tip of the tongue became visible between the lips immediately after palate closure. In the present study the rotational changes observed in skeletal tissue provided information about soft tissue changes during palatal closure. These normal developmental aspects are discussed in relation to skeletal deviations in congenital cleft palate malformations. PMID- 8478416 TI - The development and morphology of the incisive fissure and the transverse palatine suture in the human fetal palate. AB - The incisive fissure and the transverse palatine suture are well known anatomical structures in the human palate. The purpose of the present study was to describe the development and the morphology of the incisive fissure and the transverse palatine suture. Another purpose was to compare the nature of both structures with the aim of elucidating their possible function in the developing facial skeleton. Descriptions of the initial formation, development, and maturation of the incisive fissure and the transverse palatine suture, in combination with a comparison between the suture systems, were not found in the literature. Human fetal material, consisting of a total number of 96 specimens with gestational ages ranging from 9 to 24 weeks, was analyzed macroscopically (radiologically and after devisceration) and microscopically (histologically). The bony maturation of specimens was recorded by relating to the stages of maxillary ossification (MAX), an index for skeletal maturity of the palate. The study revealed pronounced macroscopic and microscopic differences between the incisive fissure and the transverse palatine suture. The transverse palatine suture appears to be a site for anteroposterior growth of the palate. The incisive fissure has a different macroscopic and microscopic appearance and presumably has a function more closely related to the development of the dentition and the anterior part of the maxilla. PMID- 8478417 TI - Growth-related changes in familial resemblance of maxillofacial morphology. AB - We investigated changes in resemblance between Japanese parents and their growing children with regard to maxillofacial morphology. Lateral roentgenographic cephalograms taken from 963 children (336 male and 627 female) over 6 years of age and their parents were used as samples. Based on the age of the children, there were six groups--I: 6-7 years of age; II: 8-9; III: 10-11; IV: 12-13; V: 14 15; and VI: over 16. Parent-offspring heritabilities (h2) were computed for 35 variables representing maxillofacial and dentoalveolar traits, and group comparisons were also made. The following results were obtained: (1) there were more significant heritabilities for maxillofacial variables than those for dentoalveolar ones; (2) in general, additive genetic effects were more prominent in controlling maxillofacial and dentoalveolar structure of on-growing children, with increasing age. PMID- 8478418 TI - Finite element method analysis of craniofacial morphology in unilateral cleft lip and palate prior to palatoplasty. AB - The craniofacial morphology in unilateral cleft lip and palate (UCLP) prior to palatoplasty was analyzed with the finite element method (FEM). The study examined cross-sectional data sets of affected and control males aged 4.5 to 6.0 years from Czechoslovakia. The facial skeleton and cranial base were discretized into 26 two-dimensional, triangular finite elements. Cranial base morphology is altered in UCLP. The extensive nature of most craniofacial deformities means that almost any registration is likely to be distorted. The fundamental advantage of the FEM is that biological descriptions are not dependent upon the selected reference plane. The FEM localizes changes in form to discrete anatomical regions. Significant shape and size differences characterize UCLP prior to palatoplasty. Dramatic deformations associated with cheiloplasty are localized to the lips and maxillary alveolar process. Nasal deformation reflects loss of structural support for the nose. PMID- 8478419 TI - Facial growth and development in unilateral complete cleft lip and palate from palate surgery up to adulthood. AB - Mixed longitudinal and cross-sectional roentgen-cephalometric data were used for studies of the growth and development of the face in unilateral complete cleft lip and palate from the time of primary palatoplasty up to adulthood. The results were compared with the data obtained in controls at the age of 5 years and in adults. The vertical growth of the upper and lower face exceeded its sagittal growth. The lower face showed a higher growth rate in both directions than did the upper face. The depth of the maxilla showed the lowest growth rate. The height of the upper lip increased very little as well. The most important deviation in facial development consisted of the deficient growth of maxillary depth and the prolongation of the lower face. Both these deviations develop predominantly after palate surgery and the former resulted in a gradual retrusion of the maxilla, a flattening of the face, and impairment of sagittal jaw relations. The reduction of upper face height, the posterior position of the maxilla, and the shortening of the mandible (both of the body and ramus) represented, on the contrary, early changes. The a persisting posterior rotation of the mandible, changes in the shape of the mandible, and vertical disproportion of the face increased with age, the steep slope of the mandibular body remaining at the level ascertained in early childhood. An improvement in the occlusion of incisors was obtained prior to the age of 12 years, but it regressed during the period of puberty. The prominence of the upper lip gradually decreased and the lip was short. PMID- 8478420 TI - Effects of 5-fluorouracil on collagen synthesis during quail secondary palate development. AB - A study was undertaken to examine the involvement of collagen synthesis during palate development in quail where mammalian-type shelf reorientation is absent. Teratological observation showed that 100 micrograms 5-fluorouracil (FU) on day 4 of incubation increased the gap between the palatal shelves. Light microscopic observation indicated that the quail palatal shelves develop as horizontal ridges on day 5 and approximate on day 8 of incubation but never fuse. FU treatment affected the approximation of palatal shelves. In separate experiments, both the control and FU-treated quail embryonic palates, which were dissected between days 5 and 10 of incubation, were incubated in a growth medium supplemented with 14C proline. The rate of collagen synthesis, total protein, hydroxyproline (HYP) levels, and collagen isotype were determined. The result showed that in control palates the rate of collagen synthesis increased fivefold between days 6 and 8 of incubation but dropped thereafter. In FU-exposed palates, the rate of collagen synthesis was lower than that in controls. It increased threefold between days 7 and 8 of incubation. High performance liquid chromatographic measurement of HYP levels indicated that, in comparison to controls, HYP accumulation in FU-treated palates was reduced by 50% on day 6 and 75% on day 8 of incubation. Total protein content in FU-treated palate were also 50-70% lower than those in their control counterparts between days 5 and 10 of incubation. Gel electrophoresis showed that only type I collagen was synthesized in the developing palate of both the control and FU-treated quail embryo. An analysis of results of the present study, along with the data from literature on mammals, corroborate the proposition that an increased collagen synthesis may contribute to the acquisition of volume of vertebrate's secondary palatal shelf for its continuing morphogenesis. PMID- 8478421 TI - Effects of amrinone on shortening velocity and force development in skinned skeletal muscle fibres. AB - The effects of amrinone were studied on single skinned fibres isolated from rat hindlimb muscles. In each fibre a force-velocity relation was determined during maximal calcium activation (pCa = 4.45) in control conditions and in the presence of amrinone. The MgATP concentration was 3.93 mM, close to the physiological value. After the experiment the fibre was classified as fast or slow on the basis of its reactivity with anti-myosin monoclonal antibodies. In fast fibres amrinone (3 mM) potentiated isometric tension (Po) by 13.8 +/- 2.9% (n = 13), reduced maximum shortening velocity (Vmax) by 32.6 +/- 3.2% and the curvature of the force-velocity relation (a/Po) was increased by 98.9 +/- 46.0%. All these effects were less pronounced in slow fibres, where Vmax was reduced only by 11.4 +/- 3.6 (n = 16). The effects of amrinone (0.3-6 mM) on the ATPase activity of myofibrils and myosin prepared from fast (tibialis anterior) and slow (soleus) rat skeletal muscles were studied. Amrinone was found to depress Ca-Mg dependent ATPase activity of myofibrillar preparations of the tibialis anterior (up to 16.6 +/- 2%) and, to a lesser extent, of the soleus (up to 7.2 +/- 1.2%). On the contrary, Ca-stimulated myosin ATPase activity was significantly increased by amrinone in myosin preparations from the tibialis anterior. Experiments were carried out to test whether amrinone (3 mM) might affect the sensitivity of the contractile system to MgATP concentration ([MgATP]). The results obtained showed that (1) the [MgATP] value at which isometric tension reached its maximum was shifted by amrinone from 0.1 mM to 0.3 mM, (2) the slope of the negative relation between [MgATP] and a/Po was made more steep by amrinone, and (3) the Km of the hyperbolic relation between [MgATP] and Vmax was increased from 0.39 to 1.71 mM by amrinone, thus indicating a reduced affinity of myosin for MgATP. These results are in accordance with the hypothesis that amrinone exerts a direct effect on the contractile mechanism. PMID- 8478422 TI - Migration of lacZ positive cells from the tibialis anterior to the extensor digitorum longus muscle of the X-linked muscular dystrophic (mdx) mouse. AB - C2 mouse myogenic cells carrying the lacZ gene coding for beta-galactosidase (beta-gal) were injected into the tibialis anterior muscle of dystrophin deficient mdx mice. Introduced cells were shown to have been incorporated into fibres of the injected muscle by virtue of the colocalization of beta-gal and dystrophin within them. Synthetic Nuclepore membrane inserted between the injected tibialis anterior and adjacent extensor digitorum longus muscle permitted the visualization of cells migrating between the two muscles through the pores of the membrane. Although the exact nature of the cells passing through the Nuclepore could not be determined by this method, they were thought to include implanted myogenic cells. Evidence for this was gained by the presence of beta-gal/dystrophin positive fibres within the extensor digitorum longus. Incorporation of cells into the adjacent extensor digitorum longus was greater in animals where this muscle had been autografted by the cutting and resuturing of the distal tendon. Autografted extensor digitorum longi differed from those which had not been subject to this procedure, by undergoing extensive fibre degeneration followed by regeneration, and further by the stripping of their surrounding epimysial covering. Implanted cells substantially participated in extensor digitorum longus fibre formation in these mice, up to 31% of their fibres 3 weeks after implantation coexpressing both the introduced lacZ gene product and the dystrophin gene product, the latter not normally expressed within the fibres of this myopathic recipient. PMID- 8478423 TI - Lack of dystrophin but normal calcium homeostasis in smooth muscle from dystrophic mdx mice. AB - The free cytosolic Ca2+ concentration ([Ca2+]i) in the dystrophin-lacking smooth muscle from mdx mice was studied to gain new insights into the relation between dystrophin and cytoplasmic Ca2+ homeostasis, which was reported to be impaired in the mdx skeletal muscle. We observed that [Ca2+]i, as measured with the fluorescent Ca2+ indicator fura-2, was not elevated in resting smooth muscle of the vas deferens from mdx mice, in comparison with control C57 mice. Changes of the external Ca2+ concentration evoked similar changes of [Ca2+]i in mdx and control vas deferens. During contraction, cytosolic Ca2+ transients were identical, both in amplitude and in kinetics, whether or not dystrophin was present. Stretches evoked similar Ca2+ increases in muscles from both strains. Intracellular Ca2+ homeostasis appears to be unimpaired in mdx smooth muscle. Thus, the lack of dystrophin per se does not automatically induce a perturbation of Ca metabolism in muscle cells. PMID- 8478424 TI - Tension transients in skeletal muscle fibres of the frog at varied tonicity of the extracellular medium. AB - Length steps (complete in 0.2 ms; amplitude < 2% of the fibre length) were applied during the tetanus plateau of intact frog muscle fibres (1.7-3.2 degrees C). The effects of varied tonicity on the early changes in tension in response to the length steps were studied. The solutions were made hypotonic by reduction of the NaCl concentration from 115.5 mM to 92.4 mM and hypertonic by addition of 98 mmol sucrose per litre of the normal Ringer fluid. In all solutions tested, the length step first caused tension to change simultaneously with the step reaching an extreme value T1. After completion of the length change, tension recovered quickly to an intermediate level T2 and, after a period with slowing or reversal of the recovery, it returned slowly to the steady-state value. The maximum isometric tension was significantly reduced by increases in tonicity. In contrast, there were only small effects of varied tonicity on the peak tension change in response to a length step (the stiffness) and on the amplitude of the fast force recovery (T2-T1) after releases. The slope of the T2-curve (a plotting of T2 versus amplitude of the length step) was reduced for releases and increased for stretches when tonicity was raised. Furthermore, the T2-curve intersected the length axis for smaller releases at high tonicity levels. The reduced isometric tension to stiffness ratio at raised tonicity could be interpreted as a reduced average force per crossbridge. Simulations using the crossbridge model of Huxley and Simmons (1971) showed that the lack of change of the recovery amplitude (T2 T1) after releases and the changes in the T2-slope are in accordance with this interpretation. The shift of the T2 length intercept is consistent with the idea that the distance traversed by the crossbridges during the power-stroke is reduced by raised tonicity. PMID- 8478425 TI - In vitro production of enzymatically active myosin heavy chain. AB - In order to initiate studies on the structural and functional relationships of the myosin heavy chain, we constructed a full-length complementary DNA encoding the isoform that is found in the fast white muscle of the embryonic chicken. The complementary DNA contained 108 basepairs of its 3'-untranslated region and was preceded by a leader sequence derived from the alfalfa mosaic virus. Similarly, a complementary DNA encoding 963 amino acids which encompass the subfragment-1 of myosin and part of the subfragment-2 was also constructed. Each was inserted into the expression vector pMT2 and transiently transfected into COS-1 cells. Both constructs directed the expression of the respective proteins, each of which was immunogenic. The full-length and subfragment-1 proteins interacted with actin and demonstrated high levels of a K(+)-activated, EDTA-resistant ATPase activity, which is characteristic of myosin. PMID- 8478426 TI - Functional effects of LC1-reassociation with cardiac papain Mg.S1. AB - The effect of LC1 on cardiac myosin structure and activity was investigated using as a model S1 prepared by papain digestion in the presence of Mg2+. The resulting S1 contained LC2 but a part of the N-terminal region of LC1 was cleaved. Sequencing the N-terminal part of the band migrating below LC1 on SDS gels revealed it to consist of alternating alanyl and prolyl residues thus establishing LC1 as the origin of this band. However, Western blots did not reveal any LC1 while radioimmunoassays indicated it to be present at the 5% level suggesting the anti-LC1 antibody used in these experiments did not recognize the C-terminal portion of LC1 still attached to Mg.S1. Mixing a 10-15 M excess of isolated light chains with Mg.S1 in the presence of 10 mM ATP, 12 mM MgCl2, 4.7 M NH4Cl allowed LC1 to recombine with LC1-deficient Mg.S1. Equilibrium ultracentrifugation analysis revealed a highly heterogeneous LC1-deficient S1 which upon recombination with intact LC1 became monodisperse as indicated by the superimposition of molecular weight averages all across the centrifuge cell. LC1 deficient Mg.S1 had a Vm of 0.4 s-1, Ka of 30 microM and a Kbind of 28 microM. In the presence of intact LC1, Vm rose to 0.8 s-1 while Ka and Kbind were reduced to 7.5 and 12 microM, respectively. The fourfold decrease in Ka strongly indicated an increased affinity for actin by Mg.S1 in the presence of uncleaved LC1. Also, Ca(2+)-regulation of dog heart myofibrils was suppressed when Ca(2+)-activated MgATPase assays, as a function of Ca2+, were performed in the presence of anti LC1 antibodies. These observations suggest the presence of intact, uncleaved LC1 in S1 is required for the stability of S1 heavy chains and proper Ca(2+) regulation. PMID- 8478427 TI - Regional differences in organization of the extracellular matrix and cytoskeleton at the equator of chicken intrafusal muscle fibres. AB - Equatorial regions of chicken intrafusal fibres were examined with a panel of monoclonal antibodies against intracellular proteins and components of extracellular matrix to identify structural associations at points of contact between sensory terminals and intrafusal fibres, and at points which lacked them. One aspect of this study was to establish whether the known morphological differences between myosensory and neuromuscular junctions also extended to the molecular level. As viewed in cross-sections, myosensory junctions at the equator are restricted to approximately one-half of the intrafusal fibre circumference, a region referred to as the sensory sector. The diametrically opposite region which lacks sensory terminals is referred to as the non-sensory sector. The basal lamina over the sensory sector was positive for chondroitin sulphate, while that part which covered the non-sensory sector was negative. Staining for collagen type IV was very faint at the sensory sector and stronger at the non-sensory sector, but immunoreactivity for heparan sulphate proteoglycan and laminin was moderate to strong in all parts of the basal lamina. Within intrafusal fibres, filamin and alpha-actinin were largely limited to the sensory sector. The major feature of the non-sensory sector was a sharply delineated, narrow intrafibre crescent of vinculin, and colocalized with it, a crescent of talin. The plasmalemma of intrafusal fibres at the non-sensory sector reacted positively for the beta 1 subunit of the integrin family of receptors. Immunolocalization of these receptors was not observed to any significant extent in the sensory sector. Towards the end of the equator and the initial portion of the juxtaequator, chondroitin sulphate, vinculin and the other proteins came gradually to be distributed equally all the way round the intrafusal fibres. This changeover in distribution of connective tissue proteins and structural intracellular proteins parallels the decreasing number of contacts made by sensory terminals. PMID- 8478428 TI - Changes in morphological and functional characteristics of male rat EDL muscle during growth. AB - Morphological and functional changes as well as changes in fibre-type composition were investigated in the left extensor digitorum longus (EDL) muscles of male Wistar rats of approximately 40, 60, 120 and 700 days old. A number of morphological changes occurred in the EDL muscle during growth. While from 40 to 120 days muscle mass and cross-sectional area (CSA) increased by 247 and 192%, changes in muscle and fibre lengths were much smaller (44 and 17%, respectively). Besides morphological changes tetanic force was also found to increase (approximately 307%) up to 120 days. Because this increase in force was greater than the increase in CSA, specific force increased by approximately 29% between 40 and 60 days. Thereafter, specific force stayed rather constant. From 40 until 60 days changes were also found in the force-frequency and force-velocity curve, which indicate a slowing of the muscles (until 60 days). Changes in fibre-type composition of the EDL muscle were found to occur later during growth between 60 and 120 days. In this period an increase in the relative total area of Type IIBd fibres and a decrease in the relative total area of Type IIBm fibres (corresponding to the Type 2X and IIB fibres, respectively), were found; this was apparently due to a conversion of many Type IIBm into Type IIBd fibres and not to a difference in cross-sectional growth between these fibres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478429 TI - Electron microscopic images suggest both ends of caldesmon interact with actin filaments. AB - An improved rotary shadowing technique enabled us to visualize chicken gizzard caldesmon (CaD) and its complexes with one or two covalently linked calmodulin (CaM) molecules by electron microscopy. Using a monoclonal antibody against an epitope in the N-terminal region of CaD (anti-N), we can now identify the end of the molecule that is involved in binding to another protein molecule. Thus in the 1:1 complex of CaD and CaM, the CaM molecule was almost always associated with the C-terminus of CaD, indicating preferential CaM-binding to the C-terminal region. We have also studied binding of CaD to filamentous actin (F-actin), using an EM technique that avoids spraying or freeze drying and thereby preserves the structure of F-actin. Only one end of CaD appeared to bind to F-actin, leaving the rest of the molecule projecting away from the filament. While the majority of anti-N bound at the free end of CaD, some antibody molecules were found on F actin. These findings suggest that either end of CaD can bind to F-actin. Experiments using a monoclonal antibody against the C-terminus of CaD (anti-C) supported this idea. When the native thin filaments that contain endogenous CaD were incubated with anti-N, almost all the bound antibodies were found on the filaments, indicating that the N-terminal regions of CaD interact with actin, and that the binding affinity of the N-terminal region of CaD for actin is higher in vivo than that in vitro, either because the properties of CaD have been altered during purification, or because of the presence of some other component(s) associated with the native filaments. PMID- 8478430 TI - Force-calcium relations in skinned twitch and slow-tonic frog muscle fibres have similar sarcomere length dependencies. AB - The sarcomere length (SL) dependence of the calcium sensitivity of force was measured in skinned single twitch and slow-tonic muscle fibres from frog and toad. Twitch and slow-tonic fibres were characterized by location, appearance, physiological response to calcium and by protein band patterns from sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Force-calcium relations were determined for each fibre type at two sarcomere lengths, 2.4 and 3.1 microns. Bathing solution ionic strength (IS) was 200 mM and solution pH was 7.0, 6.0 or 5.5; experiments were also done at IS = 120 mM and pH 7.0. At all pHs and ionic strengths tested, slow-tonic fibres exhibited a slower time course of force development and were more sensitive to calcium than were twitch fibres. Lowering IS increased calcium sensitivity and lowering pH decreased calcium sensitivity in both fibre types. Increasing SL increased the calcium sensitivity of force in both twitch and slow-tonic fibres at pH 7.0 and at both 200 and 120 mM IS. Lowering pH caused a decrease in the length dependence of calcium sensitivity of both fibre types; at pH 5.5 the calcium sensitivity of force in slow-tonic fibres exhibited a slight decrease with increasing SL. PMID- 8478431 TI - Ca-EGTA affects the relationship between [Ca2+] and tension in alpha-toxin permeabilized rat anococcygeus smooth muscle. AB - The relationship between calcium concentration ([Ca2+]) and force in smooth muscle can be studied by permeabilizing the sarcolemma and bathing the preparation in a mock intracellular solution. Normally [Ca2+] is set in these solutions using the Ca2+ chelator EGTA in the concentration range of 4-10 mM. This study shows that lowering total EGTA concentration ([EGTA]t) below 10 mM depresses Ca(2+)-activated force generated in 0.1 microM Ca2+. The observed threshold for the effect of EGTAt is 0.2 mM, and the effect is maximal at approximately 10 mM. BAPTA, another Ca2+ chelator, also produces this effect. Tension production in smooth muscle is controlled by acto-myosin interaction. This in turn is mediated by the relative activities of myosin light chain kinase (MLCK) and phosphatase (MLCP). Inhibiting MLCP with Microcystin LR (10 microM), an increase [EGTAt] from 0.2 mM to 10 mM still enhanced force. This suggests that EGTA promotes phosphorylation of myosin by the activation of MLCK and not by inhibition of MLCP. PMID- 8478434 TI - Construction of a bite plane with light-cured resin. PMID- 8478432 TI - A non-flight muscle isoform of Drosophila tropomyosin rescues an indirect flight muscle tropomyosin mutant. AB - The tropomyosin I(TmI) gene of Drosophila melanogaster encodes two isoforms of tropomyosin. The Ifm-TmI isoform is expressed only in indirect flight and jump muscles; the Scm-TmI isoform is found in other muscles of the larva and adult. The level of Ifm-TmI is severely reduced in the flightless mutant Ifm(3)3, which also is unable to jump. To explore the functional significance of tropomyosin isoform diversity in Drosophila, we have used P element-mediated transformation to express Scm-TmI in the indirect flight and jump muscles of Ifm(3)3 flies. Transformants gained the ability to jump and fly. The mechanical properties of isolated indirect flight muscle myofibres, and the ultrastructure of indirect flight and jump muscles from the transformants were comparable to wildtype. Thus, the Scm-TmI isoform can successfully substitute for Ifm-TmI in the indirect flight and jump muscles of the Ifm(3)3 strain. PMID- 8478435 TI - Modified lingual lever arm technique. PMID- 8478433 TI - Developmental transitions in the myosin patterns of two fast muscles. AB - Transitions in myosin patterns were examined in situ by immunofluorescence in two fast muscles of the developing chicken, the pectoralis and the posterior latissimus dorsi. Myosin isoforms were localized using stage-specific monoclonal antibodies against the heavy chain of pectoralis myosin. Two antibodies (12C5 and 10H10) recognize adult and late embryonic myosin. They reacted weakly with both the pectoralis and posterior latissimus dorsi at 10 days in ovo, but intensely at 18 days in ovo. Both muscles were completely unreactive with an adult-specific antibody (5C3), indicating that the staining with 12C5 and 10H10 at 18 days in ovo reflects embryonic myosin. Thus two different embryonic isoforms are expressed sequentially in each muscle. Both 12C5 and 10H10 reacted weakly again with these muscles after hatching. The reappearance of a strong positive response to both antibodies, at 28 days in the pectoralis and after 60 days in the posterior latissimus dorsi, correlated well with the first appearance of a response to the adult-specific antibody, 5C3, signalling the beginning of the adult pattern. Both muscles reacted strongly with an antibody (5B4) specific for 'neonatal' myosin between 18 days in ovo and 60 days after hatching. In the pectoralis, embryonic was replaced by neonatal myosin in most fibres by 14 days after hatching; by 28 days, both adult and neonatal myosin were expressed in most fibres; and in the adult, neonatal myosin was replaced entirely by the adult isoform. In contrast, many fibres in the posterior latissimus dorsi still expressed both embryonic and neonatal myosins up to at least 60 days post-hatch, and the remaining fibres expressed the neonatal isoform; the neonatal isoform was present in some fibres even in the adult posterior latissimus dorsi. We have therefore demonstrated in situ four different heavy chain isoforms in two different fast muscles. 'Early embryonic', 'late embryonic', 'neonatal' and eventually 'adult' isoforms are expressed in each muscle and more than one isoform often coexists in the same fibre. PMID- 8478436 TI - Direct bonding with reduced acid etchant concentrations. PMID- 8478437 TI - Ten tips for improving your case acceptance ratio. PMID- 8478438 TI - Essix retainers: fabrication and supervision for permanent retention. PMID- 8478439 TI - Periodontal plastic surgery and orthodontics. PMID- 8478440 TI - Endovaginal Doppler flow measurements of the ovarian artery in patients with a normal menstrual cycle and with polycystic ovary syndrome during in vitro fertilization. AB - Women with a normal menstrual cycle (n = 21, controls), polycystic ovary syndrome (n = 10) and hypogonadotropic amenorrhea (n = 3) were stimulated with clomiphen citrate (4th day to 8th day of the cycle) and with human menopausal gonadotropin (8th day to 11th day). The vascular impedance of the ovary carrying the dominant follicles was monitored by endovaginal pulsed Doppler flow measurement. Simultaneously, serum levels of LH, E2 and 17-OHP were assayed. Contrary to controls, women with polycystic ovary syndrome or hypogonadotropic amenorrhea showed decreased hormone levels and no lowering of the vascular impedance. In controls, the lower pulsatility index is caused by neovascularization around the dominant follicle and by E2-induced vasodilatation in the ovarian artery. PMID- 8478441 TI - Transient renal medullary hyperechogenicity in ultrasound studies of neonates: is it a normal phenomenon and what are the causes? AB - A prospective ultrasound study of the renal morphology of 51 neonates with no clinical signs of renal impairment showed transient medullary hyperechogenicity of varying intensity in 37%. These findings were made in the first few postnatal days, were not accompanied by any other echographic changes, and disappeared again within the first week of life. They were encountered twice as often in full term as in premature babies. In parallel with this phenomenon, the concentration of Tamm-Horsfall protein, calcium, and uric acid, and the osmolality were determined in the daily urine of 44 of these neonates. The analyses did not provide any definite clues as to the etiology of the ultrasound findings. It is therefore suggested that the term "Tamm-Horsfall nephropathy or proteinuria" should no longer be used for such sonographic phenomena in the neonatal kidney, but rather, they should be regarded as normal. Furthermore, the term "tubular stasis nephropathy" should be reserved for cases with clinically demonstrable impairment of renal function. PMID- 8478442 TI - The assessment of normal early pregnancy by transvaginal color Doppler ultrasonography. AB - Transvaginal color Doppler was performed in 198 volunteer pregnant women whose menstrual age ranged from the fifth to the twelfth week. In all patients an attempt was made to obtain signals from both uterine arteries, peritrophoblastic/retroplacental vessels, umbilical arteries, fetal aorta, intracranial vessels, and corpus luteum flow. With the combination of color and pulsed Doppler transvaginal sonography, detection of vascular structures was greatly facilitated and the amount of time for examination significantly reduced. Flow velocity waveforms were measured and results were analyzed by calculation of the Resistance Index. During the early stage of pregnancy, we were able to locate both uterine arteries in all cases and continuous diastolic shift signal was found. Flow in the peritrophoblastic/retroplacental area was observed with an overall success rate of 94%. Blood flow in the umbilical artery and fetal aorta was visualized by color Doppler starting from the seventh week. Intracranial blood flow could be visualized starting from the tenth week in some cases. Diastolic flow in these vessels was detectable starting from the twelfth week. Corpus luteum flow was found in 148 cases (75%) and the Resistance Index decreased as pregnancy progressed. PMID- 8478443 TI - Intrascrotal adenomatoid tumors and their ultrasound findings. AB - Adenomatoid tumors are regarded as uncommon neoplasms of the paratesticular tissues, probably of mesothelial origin, and the majority of cases reported have involved the epididymis. Ultrasonography is the method of choice for imaging scrotal pathology, but there are very few data on ultrasound findings in cases of adenomatoid tumors. We report our experience and ultrasound findings regarding 8 intrascrotal adenomatoid tumors--3 cases of a testicular tunica albuginea tumor and 5 cases of epididymal origin. Ultrasonography is recommended as the preoperative imaging method for excluding the possibility of a cystic lesion and for determining the location of the tumor. Local excision is regarded as the treatment of choice. The clinical course of all these tumors was benign, without recurrences. PMID- 8478444 TI - Intracystic papilloma in male breast: ultrasonography and pneumocystography diagnosis. PMID- 8478445 TI - Atypical renal hamartomas: ultrasonography, computed tomography, and angiographic findings. PMID- 8478446 TI - Aspiration of acute calcerous trochanteric bursitis using ultrasound guidance. PMID- 8478447 TI - Clinical findings and endosonographic appearance of endometriosis in the anal sphincter. PMID- 8478448 TI - Sonographic diagnosis of an inflamed urachal cyst. PMID- 8478449 TI - Ultrasound-directed diagnosis and treatment of pelvic hematoma after therapeutic abortion. PMID- 8478450 TI - Recurrent transient gallbladder wall thickening associated with interleukin-2 chemotherapy. PMID- 8478451 TI - First trimester transvaginal sonographic diagnosis of Dandy-Walker malformation. PMID- 8478452 TI - Left heart obstructive disease with ventricular hypoplasia: changes in the echocardiographic appearance during pregnancy. PMID- 8478453 TI - Ultrasound appearance of gas bubbles in hepatic veins after orthotopic liver transplantation: a phenomenon with consequences? PMID- 8478454 TI - Image-directed Doppler ultrasonography: a novel technique for the diagnosis of colorectal liver metastases. AB - Image-directed Doppler ultrasonography has been used to measure changes in hepatic arterial and portal venous blood flows in 22 controls and 88 patients with colorectal cancer. Doppler Perfusion Index, (DPI, ratio of hepatic arterial to total liver blood flow) and Doppler Flow Ratio (DFR, ratio of hepatic arterial to portal venous blood flow) of controls and patients with overt liver metastases were clearly separated (p < 0.0001). There was a significant reduction in the Hepatic Arterial Resistive Index (HARI) of patients with overt liver metastases (p < 0.0001). Percentage Hepatic Replacement (PHR) by metastases, measured using a computed tomography scanner, did not correlate with DFR or DPI. The results suggest that the measurement of hepatic perfusion changes using image-directed Doppler ultrasonography may be of value in the detection of small liver metastases. PMID- 8478455 TI - Sonourethrography in the evaluation of anterior urethral strictures: correlation with radiographic urethrography. AB - A total of 30 patients with suspected urethral strictures underwent sonographic and roentgenographic urethrograms. Two patients showed a normal anterior urethra in the sonourethrogram; 29 strictures were diagnosed in the remaining 28 patients, 1 patient showing strictures at two different sites. Sonourethrography was an accurate predictor of stricture length, retrograde urethrography underestimating the stricture length in most of the cases. Periurethral structures, including the urethral wall, corpus spongiosum, corpora cavernosa, bulb, and external urinary sphincter, were seen clearly with sonourethrography. Periurethral fibrosis was seen in 16 patients and graded as mild (n = 5), moderate (n = 2) or severe (n = 9), depending on the depth of involvement of the corpus spongiosum. Sonourethrography was unsatisfactory in the evaluation of membranous strictures, failing to visualize the proximal limit of the stricture. PMID- 8478456 TI - Myoma vs. contraction in pregnancy: differentiation with color Doppler imaging. AB - During pregnancy, leiomyomas may cause complications such as spontaneous abortion, premature labor, and obstruction of labor. The conventional real-time ultrasound examination usually detects myomas adequately, but, in some cases, a local thickening of the uterine wall persists throughout the examination, interfering with the differentiation between myoma and contraction. In such cases, repeat scanning approximately 30 minutes later differentiates contractions, which usually resolve, from myomas. We examined 10 patients with B mode and color Doppler ultrasonography. In the 5 patients with myoma, we observed splaying of the vessels around the mass, whereas in the 5 patients with contraction, there was no vessel displacement in the area of the local myometrial thickening. The use of color Doppler and observation of these findings may obviate a prolonged ultrasound examination in questionable cases. PMID- 8478457 TI - Ultrasonic signs of pneumothorax: preliminary work. AB - Ultrasonography is considered to have limited application in respiratory diseases because air reflects sound waves. Twenty-four patients with radiologically confirmed pneumothorax and 100 healthy subjects underwent sonography. In all normal subjects, the hyperechoic pulmonary interface showed respiratory motions termed the "gliding sign" with some comet-tail artifacts. Sonographic signs were shown in all pneumothoraces: disappearance of the gliding sign and no comet tails. The extent of collapse cannot be evaluated, but it is possible to determine its area in partial pneumothorax (N = 5). The follow-up (N = 8) showed the reappearance of the gliding sign. Ultrasonography may be helpful in diagnosing pneumothorax in certain cases. PMID- 8478458 TI - Ultrasonography and biliary extracorporeal shock-wave lithotripsy. AB - The results of shock-wave treatment of gallbladder stones depend to a very high degree on the quality and expertise of ultrasonography applied before, during, and after shock-wave disintegration of the stones. Ultrasonography is decisive in evaluating the inclusion criteria; it is the method of choice for directing the shockwave energy at the stones and monitoring the disintegration process. It is the only diagnostic modality to really demonstrate the gallbladder being free from stones. PMID- 8478460 TI - Tuberculosis of the lower genitourinary tract: ultrasonography as an aid to diagnosis and treatment. PMID- 8478459 TI - The effect of drainage of fetal chylothorax on cardiac and blood vessel hemodynamics. PMID- 8478461 TI - Ultrasonic diagnosis of acute uncomplicated appendicitis located in the subhepatic space. PMID- 8478462 TI - Megaureter associated with severe renal dysplasia. PMID- 8478463 TI - Prenatal diagnosis of congenital pyloric atresia. PMID- 8478464 TI - Periportal and retroperitoneal sarcoidosis. PMID- 8478465 TI - Retroperitoneal sarcoidosis. PMID- 8478466 TI - Gossypiboma: diagnosis with ultrasonography. PMID- 8478467 TI - Intraoperative transrectal ultrasonography in the management of ejaculatory duct obstruction caused by midline prostatic cyst. PMID- 8478468 TI - What's new in cutaneous laser surgery. PMID- 8478469 TI - Pulsed dye laser treatment of vascular lesions in children. AB - BACKGROUND: The flashlamp-pumped pulsed dye laser (577,585 nm) with 300 to 450 microseconds pulsewidths has been demonstrated to effectively and safely treat port-wine stains, telangiectases, and superficial hemangiomas in children. OBJECTIVE: The objective of this manuscript is to review the indications of the pulsed dye laser in the treatment of vascular lesions in children. CONCLUSION: Pulsed dye laser treatment of port-wine stains can remove or lighten the lesions with multiple treatment sessions. Spider telangiectases respond with complete resolution, usually within one to two treatment sessions. Superficial hemangiomas respond quite easily and effectively with the pulsed dye laser, while a more variable response is noted in deeper hemangiomas, early proliferative lesions, and ulcerated hemangiomas. This procedure is safe with a low incidence of scarring and pigmentary alteration. PMID- 8478470 TI - Clinical usefulness of the Hexascan. Treatment of cutaneous vascular and melanocytic disorders. AB - BACKGROUND: The Hexascan is an automated scanning laser handpiece originally developed to treat port-wine stains. It can be adapted to operate with most continuous wave laser systems delivering a variety of visible wavelengths. OBJECTIVE: To review the use of Hexascan with 585-nm yellow dye laser light for cutaneous vascular disorders and 514-nm green argon light for benign cutaneous melanocytic disorders. METHODS: The current clinical results, treatment parameters, indications, limitations, and complications of these procedures are discussed in a review format. In addition, a new clinical study of benign lentigines treated with green laser light is presented. RESULTS: Most benign lentigines showed considerable lightening or complete disappearance after one or two treatments. Other melanocytic disorders may also respond. Deep dermal lesions such as Nevus of Ota may be totally unresponsive. Both vascular malformations such as port-wine stains and hemangiomas are also treatable. CONCLUSION: The Hexascan device attached to a continuous wave tunable dye laser can successfully treat a wide variety of cutaneous vascular and melanocytic disorders in both infants and adults. PMID- 8478472 TI - Clinical use of the Q-switched ruby and the Q-switched Nd:YAG (1064 nm and 532 nm) lasers for treatment of tattoos. AB - BACKGROUND: The desire to remove tattoos has probably been around as long as their existence. Recent technological advances in lasers have finally made it possible to remove tattoos without leaving an equally undesirable scar. OBJECTIVE: The purpose of this article is to review the use of the Q-switched ruby (694 nm) and the Q-switched Nd:YAG (532 and 1064 nm) lasers for effective removal of tattoo ink, with cosmetically appealing results. RESULTS: The Q switched ruby laser (694 nm) effectively removes blue-black and green ink, may treat other colors less efficiently, and is frequently associated with transient pigmentary changes, including rare depigmentation. The Q-switched Nd:YAG laser at 1064 nm quickly removes black ink, as well as other colors less efficiently; pigmentary changes are much less frequent, correlating with its lower absorption by melanin. The 532-nm wavelength treats red ink effectively, but also leads to temporary hypopigmentation. Transient textural changes may be noted at all three wavelengths discussed, but scarring is rare. CONCLUSIONS: Q-switched lasers can remove tattoos without residual scarring. Efficacy of ink removal is dependent on the wavelength used for the targeted pigment. PMID- 8478471 TI - Clinical efficacy of the pulsed dye laser in the treatment of vascular lesions. AB - BACKGROUND: Increasing the selectivity of laser-induced damage is an ongoing goal for the laser treatment of cutaneous lesions. The flashlamp-pumped pulsed dye laser has significantly participated and advanced this pursuit. This is especially true in its use for the treatment of cutaneous vascular lesions. OBJECTIVE: A review of the development and current use of this laser for the treatment of cutaneous vascular lesions will be presented. METHODS: The laser has been designed to limit laser energy absorption and damage to hemoglobin and the blood vessel. This has been done by setting the wavelength at 577 to 585 nm and the pulse duration at 360 to 450 microseconds. RESULTS: The therapeutic results have been beneficial for almost all types of superficial small vessel vascular lesions regardless of lesional anatomic site or patient age. These lesions include port-wine stains, telangiectasia, capillary hemangioma, and other angiomata and vascular ectasia. Deeper cutaneous vascular processes and lower extremity telangiectases have proven to be less responsive to therapy. The increased vascular selectivity has allowed for a dramatic decrease in adverse effects when compared to previously used laser systems. CONCLUSION: Based on many thousands of treatment sessions and follow-up evaluation, the pulsed dye laser appears to have the greatest margin of safety in the treatment of cutaneous vascular lesions, especially for the pediatric population. PMID- 8478473 TI - Laser treatment of benign pigmented epidermal lesions using a 300 nsecond pulse and 510 nm wavelength. AB - Sixty-five patients having a total of 492 lesions were treated with the Candela pigmented lesion dye laser (510 nm, 300 ns). Lesions treated included cafe-au lait macules, lentigines, seborrheic keratoses, and postinflammatory hyperpigmentation. Fluences varied from 2.0 J/cm2 to 3.5 J/cm2, but averaged 2.25 J/cm2. Response was good to excellent after one treatment with 40-50% completely clearing and an additional 33% clearing by 75% or more. Repeated treatments were capable of clearing residual lesions. Histologic examination revealed vacuolization of melanin-containing cells and suprabasilar vesicles. The only adverse sequelae were transient hypopigmentation and hyperpigmentation, which resolved in 4 to 6 months. PMID- 8478474 TI - Treatment of port-wine stains for the 1990s. AB - BACKGROUND: A dramatic improvement in the treatment of patients with port-wine stains has occurred over the past 20 years owing to the availability of a variety of different laser systems. The argon laser was the first system to offer an advantage over the older surgical techniques that had previously been used to manage these patients. However, many new lasers have since been developed that further improved the treatment results while simultaneously reducing the risks, even when treating children. OBJECTIVE: To present the current status of laser surgery for port-wine stains and describe how the many newer systems are being used to more effectively manage these patients. METHODS: A thorough review of the medical literature was conducted on the use of new lasers, delivery systems, and treatment techniques for the management of port-wine stains. RESULTS: The biggest advance in laser treatment of port-wine stains resulted from the development of systems that are capable of delivering yellow light. The improved precision provided by these lasers serves to minimize epidermal injury, limit nonspecific thermal damage, and permit treatment of newborns and young children without a significant risk of scarring. CONCLUSION: Major benefits in the treatment of port wine stains have resulted from the recent development of many new laser systems and laser accessories that provide a more precise response with less potential for complications than had been previously attainable with older technologies. PMID- 8478475 TI - Clinical usefulness of the argon laser for the 1990s. AB - The argon laser remains an excellent, important laser in the 1990s. Its major role in dermatology is for the treatment of mature nodular port-wine stains, telangiectasia, small vascular lesions, and superficial pigmented lesions. Technique modifications and appropriate patient selection have been developed to maximize favorable response. PMID- 8478476 TI - Use of the carbon dioxide laser in dermatologic surgery. A clinically relevant update for 1993. AB - BACKGROUND: The effective and safe use of the carbon dioxide (CO2) laser in the 1990s has been facilitated by technologic advances and widespread clinical use producing a better understanding of laser-tissue interactions, refinements in technique, and modifications of the list of indications. Safety guidelines have evolved from identification of complications. OBJECTIVE: To discuss the basic principles and applications of CO2 laser surgery. METHODS: Types of CO2 lasers and their applications are discussed. CONCLUSION: Today, use of the carbon dioxide laser simplifies many procedures, is reasonably safe, is effective for its intended usages, and is the preferred treatment of several cutaneous disorders. PMID- 8478477 TI - The copper vapor laser for treatment of cutaneous vascular and pigmented lesions. AB - BACKGROUND: Clinical experience has shown that a variety of skin lesions are treatable with rapidly pulsed yellow and green light of the copper vapor laser. OBJECTIVE: To review the development, use, complications, and efficacy of the copper vapor laser when utilized for cutaneous lesions. METHODS: Articles were identified through a MEDLINE search, review of these articles' bibliographies, and advice from expert physicians who have used the copper vapor laser. RESULTS: A variety of vascular and pigmented cutaneous lesions are effectively treated with the copper vapor laser. A distinct advantage for hypertrophic or cobblestoned port-wine stains and most types of facial telangiectasia is seen when this laser's results are compared with the results of other available laser systems. Complications, including scarring, are rarely observed. CONCLUSION: The copper vapor laser is a useful addition to the family of lasers that are used for cutaneous conditions. PMID- 8478478 TI - Benign pigmented lesions of the skin. Treatment with the Q-switched ruby laser. AB - BACKGROUND: The Q-switched ruby laser is a 694 nanometer (red light) pulsed (20 40 nsecond) laser that has been shown to be effective in the treatment of cutaneous pigmented lesions. OBJECTIVE: This article will review my experience in the use of the Q-switched ruby laser to treat a wide gamut of epidermal and dermal pigmented lesions. RESULTS: The Q-switched ruby laser is highly effective in treating epidermal pigmented lesions and can be efficacious in the treatment of some dermal pigmented lesions. CONCLUSION: The Q-switched ruby laser is an effective addition to the cutaneous laser armamentarium. PMID- 8478479 TI - 510-nm pigmented lesion dye laser. Its characteristics and clinical uses. AB - BACKGROUND: Benign pigmented lesions are of a cosmetic concern to many individuals. Numerous treatments exist, including several types of lasers. The Candela 510 nm pigmented lesion dye laser has recently been added to this armamentarium. It is designed specifically for the treatment of superficial pigmented lesions while significantly decreasing the risk of scarring and prolonged hypopigmentation. OBJECTIVES: To describe the characteristics of the Candela pigmented lesion dye laser and report on the therapeutic outcome of patients treated for actinic lentigines, cafe-au-lait macules, melasma and red tattoos by one of the authors (RCG). METHODS: The Candela 510 nm pigmented lesion dye laser was used to treat solar lentigines, cafe-au-lait macules, melasma and red tattoo. RESULTS: Excellent outcomes resulted on facial and hand lentigines (89% and 88% of patients had greater than 75% clearing, respectively), but often required more than one treatment. Lentigines located on the upper extremities and trunk improved less dramatically. Immediate greying occurred universally. Bruising was often noted. Treatment failures have been observed especially in treating lentigines located on the lower extremities. Cafe-au-lait macules responded inconsistently, with facial lesions giving the best results. Melasma responded poorly, often with hyperpigmentation. Three red tattoos cleared. Treatment failure may be related to inaccurate clinical assessment of pigment depth or regrowth of the lesion. Several cases are presented to demonstrate clinical and histologic effects of the laser. CONCLUSION: The Candela 510-nm pigmented lesion dye laser is an effective treatment for superficial pigmented lesions. Its associated morbidity is minimal. PMID- 8478480 TI - Mini- and micrografts exclusively versus standard grafts mixed with mini- and micrografts. PMID- 8478481 TI - Electrodessication at the DIP for myxoid cyst and skin flaps in proximity to the interphalangeal joints. PMID- 8478482 TI - Autologous fat transplantation: evaluation and interpretation of results. PMID- 8478483 TI - Secondary syphilis mimicking borderline (BL) leprosy. AB - A young woman with syphilids resembling borderline lepromatous (BL) leprosy is being described. This is yet another addition to its already well-documented manifestations. The high prevalence of leprosy and syphilis augments the epidemiological significance of the case. PMID- 8478484 TI - Generalized eruptive histiocytoma: report of a pediatric case. AB - A one-year-old boy was seen with brownish, flat papules on his face, neck and upper arms. The lesions were symmetric, discrete, slightly raised, firm to the touch, and asymptomatic papular eruptions. Histological and immunohistochemical investigation revealed monomorphous infiltration of S-100 negative, lysozyme negative, and alpha 1-antitrypsin negative, but alpha 1-antichymotrypsin positive and vimentin positive histiocytic cells with small numbers of lymphocytic cells. The histiocytic cells did not show any foamy changes in the cytoplasm. No giant cells were found. The lesions increased in number during the first few years and then spontaneously regressed by the sixth year of age, leaving partial brownish pigmentation. PMID- 8478485 TI - Linear lichen planus mimicking creeping eruption. AB - A 42-year-old woman was referred to our hospital with a linear eruption on her right flank of two months duration. Because she had eaten loach-fish a month before she noticed the eruption, a creeping eruption due to Gnathostoma spp. was initially suspected, but the histological findings of the biopsy specimens showed typical features of lichen planus. Linear lichen planus is discussed based on the cases accumulated in the literature regarding the distribution of Blaschko lines. PMID- 8478486 TI - Introduction of a fluorescence-microscopic technique for the detection of eggs, egg shells, and mites in scabies. AB - A technique using the fluorescence microscope can prove helpful in the laboratory diagnosis of scabies. Specimens from fifteen patients with scabies were used in this study. All of the specimens were embedded with glycerine instead of potassium hydroxide (KOH) solution. The specimens were examined at 0 min, 30 min, 1 hr, 6 hrs, 24 hrs, and one week after mounting under light and fluorescence microscopes. Specimens embedded with non-fluorescent glycerine were not clear immediately after mounting but became so after about 1 hr. Eggs and egg shells were easily counted in the specimens under the fluorescence microscope but were very hard to identify under the light microscope. Mites were absent in half of the specimens; only eggs and egg shells were present in those specimens found by the fluorescence microscope. The above findings suggest that the detection of egg shells by the use of fluorescence microscope may be helpful for the diagnosis of scabies, in particular with mite negative specimens. Slides prepared with non fluorescent glycerine were more stable and could be preserved for a long time. However, this method is time-consuming and requires expensive equipment. PMID- 8478487 TI - Deposits of fibronectin in sclerotic fibromas of the skin. PMID- 8478488 TI - Immunotherapy of melanoma: current status and prospects for the future. AB - As one of the most immunogenic human malignancies, melanoma has served as a prototype for the development of immunotherapy against human cancer in a number of treatment modalities over the past two decades. These studies have included augmentation of host immunity with lymphokines and other biological response modifiers, lymphokine-activated killer cells, and cytotoxic T-cells; active immunotherapy using purified antigens, tumor cell vaccines, and anti-id antibodies; and passive immunotherapy with monoclonal antibodies. The results of these investigations are discussed as well as the prospect for future treatments of melanoma incorporating immunotherapeutic techniques. A report on a recent trial of gene therapy of human melanoma performed by Dr. Steven Rosenberg is also presented. PMID- 8478489 TI - Effects of ultraviolet-B and PUVA on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity in mouse skin. AB - Ultraviolet-B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet-B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet-B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet-B stimulated epidermal DNA synthesis approximately 5-fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane-bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet-B or PUVA, unlike the case with phorbol ester tumor promoter. PMID- 8478490 TI - A case of pretibial dystrophic epidermolysis bullosa: decreased expression of the non-helical domain of type VII collagen molecule. AB - A 27-year-old man with an ataxic gait due to infantile cerebral paralysis exhibited recurrent blistering caused by mechanical stimuli on the pretibial area of both legs from the age of 20. His parents were not consanguineous, and he had no relatives who suffered from blistering. The histology showed a subepidermal bulla due to dermolytic epidermal-dermal separation. The anchoring fibrils were sparse and rudimentary in the predilection area. An LH 7:2 monoclonal antibody against the non-helical domain of the type VII collagen molecule stained the basement membrane zone of the patient's skin at a weaker intensity than the staining of normal human skin, but at a distinctively stronger intensity than the staining of skin from a patient with recessive dystrophic epidermolysis bullosa. Immunoelectron microscopy revealed that LH 7:2-immunoreactants were distributed irregularly within the lamina densa and sparsely in the sublamina densa region. The patient was diagnosed with pretibial dystrophic epidermolysis bullosa. PMID- 8478491 TI - Secretion of IL-2, IL-4, and IFN-gamma for dust mite antigens in a patient with atopic dermatitis. AB - In a 21-year-old female with severe atopic dermatitis, the secretion of interleukin-2 (IL-2), interleukin-4 (IL-4), and interferon-gamma (IFN-gamma) by her peripheral blood mononuclear cells (PBMC) was measured after incubation with/without antigens extracted from Dermatophagoides pteronyssinus (Dp), to which the patient had developed a positive patch-test reaction. Incubation with Dp antigen produced marked secretion of IL-2 and IFN-gamma, but not IL-4. This may suggest that Dp-specific T lymphocytes present in the circulating blood cells are capable of producing IL-2 and IFN-gamma, which may be relevant to the delayed type allergic reaction occurring in the skin lesion. PMID- 8478492 TI - A study of the efficacy of antimicrobial detergents for hand washing: using the full-hand touch plates method. AB - We studied the effects of four kinds of antimicrobial detergents, 4% chlorhexidine gluconate (CHG), chlorbenzarconium (CBC), 10% povidone-iodine (PVI), 0.3% triclosan (TRI), and one non-medicated detergent (NMD) using the full hand touch plates method. Before and after 3 minutes of hand scrubbing with a brush, bacterial colonies on the hand surface and subungual bacteria were counted. CHG, CBC, and PVI were excellent antimicrobial detergents against hand surface bacteria, but most of the subungual bacteria remained. The subungual space was the most difficult region from which to eradicate bacteria. TRI was much less effective than hand soap against hand surface bacteria. PMID- 8478493 TI - Concomitant occurrence of circulating IgA anti-intercellular and anti-basement membrane zone antibodies in autoimmune blistering diseases: immunofluorescence and immunoblot studies. AB - Recently, cases with circulating IgA anti-intercellular antibodies have been described. The objective of this study was to present immunofluorescence and immunoblot findings in three cases of bullous diseases with concomitant circulating IgA anti-intercellular and anti-basement membrane zone antibodies. Direct immunofluorescence, indirect immunofluorescence on intact and 1M NaCl split skin, immunoblotting of epidermal extracts from dispase- and EDTA-separated (two different procedures) human skin, and immunoblotting of the bovine desmosome preparation were performed. All three cases had IgA anti-intercellular and anti basement membrane zone antibodies. However, immunoblot results were divergent. Case 1 had antibodies against the 150 kD pemphigus foliaceus antigen (IgG), the 170 kD protein (IgG and IgA), and the 97 kD antigen (IgG and IgA). Case 2 had IgG antibodies reactive with the 230 kD and the 170 kD bullous pemphigoid antigens, while case 3 had IgA antibodies against the 97 kD antigen only. The results of immunofluorescence and immunoblot studies in our patients widen the spectrum of laboratory features in blistering skin diseases mediated, at least in part, by antibodies of the IgA class. PMID- 8478494 TI - Giant-cell (temporal) arteritis following a bypass operation for cerebral infarction. AB - A 61-year-old man was referred to us with linear and indurated erythemas and severe tenderness on the scalp, neck, tongue, and scrotum which had gradually spread over the previous six months. He had a history of an intracranial bypass operation for cerebral infarction. Histologic and ultrastructural examinations revealed giant-cell arteries in the skin as well as inflammatory cells infiltrating into nerves. Carotid angiograms indicated stenosis of cranial arteries. It is suggested that the bypass operation may be related to the occurrence of the giant-cell arteritis and that the inflammatory cell infiltrate into nerves may have caused the severe tenderness of this disease. PMID- 8478495 TI - Epidermolysis bullosa acquisita (EBA) with nonclassical distribution of eruptions. AB - The skin lesions in epidermolysis bullosa acquisita (EBA), a mechanobullous disease, often show acral distribution. Recently, we experienced a case of EBA in which most of the skin lesions were located on the trunk. We reviewed the distribution of the skin eruptions in 58 reported cases of EBA. Although the extensor surfaces of the extremities are the most common site, there were some cases with non-acral distribution. These "nonclassical" cases should also be considered in the clinical diagnosis of EBA and other bullous diseases. PMID- 8478496 TI - Sexually transmitted diseases in a HIV infected patient. AB - We report a case of HIV infection with herpes simplex, syphilis, and condyloma acuminatum in a 66-year-old heterosexual man. The patient was an asymptomatic carrier (group II) of HIV infection. Herpes simplex on his penis was controlled by aciclovir. Secondary syphilis was treated with penicillin G, after which skin lesions disappeared. These four diseases were all sexually transmitted diseases (STD). One should consider the possible existence of other STD in similar cases. PMID- 8478497 TI - Childhood lichen planus (LP). AB - In adults, lichen planus (LP) is relatively more common than in children. Among 222 cases of LP, there were 25 (11.2%) children in our study. The majority of the cases were females in the age group of 8-14; the youngest child was 3 years old. Papular and linear types of LP were common in children. There was no familial history of LP in any of the cases. The patients with classic LP lesions responded well to dapsone therapy. This study supports the suggestion of Ramsay and Hurley that childhood LP is more common in the tropics. PMID- 8478498 TI - Incidental epidermolytic hyperkeratosis in progressive systemic sclerosis. AB - Incidental epidermolytic hyperkeratosis (EH) has been reported in a variety of lesions. We describe here incidental EH in a patient with progressive systemic sclerosis (PSS). We reviewed 108 skin biopsies from our cases of PSS and localized scleroderma, but this finding was seen only in the present case. Focal acantholytic dyskeratosis is analogous to EH, but we believe that this case is most consonant with EH. Since there has been no other report of EH in PSS, this association may be coincidental. PMID- 8478499 TI - Prominent telangiectasia associated with marked bleeding in CREST syndrome. AB - A 64-year-old woman with CREST syndrome developed prominent telangiectases mimicking hereditary hemorrhagic telangiectasia (HHT) of Osler-Rendu-Weber. We have been following her since she first came to us with discrete telangiectatic mats and Raynaud's phenomenon 11 years ago. Telangiectatic lesions have been seen on her larynx and esophagus in addition to commonly affected sites. She has experienced spontaneous epistaxis and marked bleeding from the lesions on her lips, oral mucous membrane, and soles. This case illuminates new aspects of telangiectasia in CREST syndrome. PMID- 8478500 TI - Eosinophilic panniculitis. AB - A 39-year-old obese female patient with borderline diabetes mellitus who developed multiple, tender, and hard nodules on the lower abdominal wall is described. The histological features were characterized by mixed panniculitis, showing massive eosinophilic infiltration and fibrosis in the septae and many foam cells in the parenchymal area of subcutaneous tissues. The eruption regressed gradually during the course of diet therapy for diabetes mellitus and obesity. Although the etiology is diverse and nonspecific, eosinophilic panniculitis seems to be a unique histopathological reaction pattern characterized by massive eosinophilic infiltration into subcutaneous tissues. PMID- 8478501 TI - Subclinical syringoma coexisting with nevocellular nevus on the vulva. PMID- 8478502 TI - Comparison of full-dose versus half-dose pharmacotherapy in the maintenance treatment of recurrent depression. AB - Recent evidence points to the prophylactic efficacy of maintaining recurrent unipolar patients on the same dose of antidepressant medication that was used to treat the acute episode (Frank et al., 1990; Kupfer et al., 1992). Therefore, the question of whether such patients should be tapered to a lower maintenance dose after successful resolution of an acute episode is clearly important. In this report we describe a small randomized clinical trial in which patients were assigned to either full-dose or half-dose maintenance treatment for a period of 3 years. Survival analysis suggests that superior prophylaxis can be achieved with a full-dose as compared to a half-dose maintenance treatment strategy (p < 0.07). Mean survival time for the full-dose subjects was 135.17 (SE 19.75) weeks as compared to 74.94 (SE 19.78) weeks (median of 43.1 weeks) for the half-dose subjects. We conclude that for patients who have suffered several recurrences, full-dose maintenance treatment is the more effective prophylactic strategy. PMID- 8478503 TI - Organic manic syndrome: causative factors, phenomenology and immediate outcome. AB - A prospective study on organic manic syndromes led to identification of 30 cases over a period of 11 months, constituting 1.75% of all admissions and 4.67% of all patients with mania. They were compared with 60 sex- and age-matched bipolar controls. The mean age of onset of illness was not significantly different in the two groups. Family history of affective disorder was more often negative in organic manics. The overall mania rating score was similar in the two groups, but after 3 months organic manics improved less. Compared to the bipolar group, organic manics were more often irritable, made threats, had delusions, and showed cognitive dysfunctions. The implications of these findings on definition of the organic manic syndrome are discussed. PMID- 8478504 TI - Inter-rater reliability of a refined index of melancholia: the CORE system. AB - We report an inter-rater reliability study of the modified 18-item, sign-based CORE index of melancholia, undertaken on 205 ratings of 35 patients by five clinical research psychiatrists. Inter-rater agreement about the presence or absence of individual items was slight to moderate when examined by the kappa coefficient, but moderate to high when examined by the intraclass correlation statistic. For total CORE scores, perhaps the most important application of the index of melancholia, high levels of intraclass correlation coefficients (ranging 0.79 to 0.90 across the varying rater dyads) were established. When a single cut off score (of 7/8) was used to allocate patients to either a 'melancholic' or 'non-melancholic' class, only moderate agreement was established between raters in such 'class' assignments--a limitation which can be redressed by imposing a 'probable/possible melancholia' band of scores. PMID- 8478505 TI - Depressed patients' parental representations: stability across changes in depressed mood and specificity across diagnoses. AB - Parental representations of a Dutch sample of psychiatric patients with diagnoses of dysthymia and unipolar depression were compared with those of a matched sample of non-depressed patients and a matched sample of healthy controls. No differences in recalled parental rearing styles were found between depressives with a diagnosis of dysthymia and those with a diagnosis of unipolar depression. Depressive did not differ from the mixed (but non-depressed) sample of psychiatric patients, whereas both the depressed and the mixed group of patients reported more adverse parenting than the healthy controls. Analysis of repeated measurements of parental representations showed that memories of parental behavior were highly stable across clinically significant changes in depressed mood, so that it seems unlikely that patients' relatively negative recollections of their parents' behavior were due to mood state dependent recall. Results are discussed within the framework of depression theories and with regard to the validity and utility of self-report instruments for parental rearing styles. PMID- 8478506 TI - Low genetic effect and age-specific family effect for symptoms of anxiety and depression in nuclear families, halfsibs and twins. AB - Questionnaire information on symptoms of anxiety/depression was obtained from 61,286 persons, most of whom could be grouped in families as spouses, parents, offspring, siblings, halfsibs and twins. The correlations between mental health in relatives, varying somewhat by sex, were: 0.27 for 18,768 pairs of spouses, 0.12 to 0.17 for 30,888 pairs of parents and offspring, 0.11 to 0.18 for 13,134 pairs of siblings, 0.27 to 0.35 for 57 pairs of MS twins, -0.06 to 0.10 for 60 pairs of DZ twins, 0.30 for 88 pairs of halfsibs reared together, and 0.16 for 40 pairs of halfsibs reared apart. The heritability was estimated to be between 0 and 0.20. There was a significant effect of environmental transmission from mother, but not from father, to offspring. The effect of environmental factors shared by sisters was substantial, the corresponding effect was lower in brothers, and zero in siblings of opposite sex. The correlations decreased with increasing age differences between relatives, implying effects of age-specific genes or environmental factors in the family. PMID- 8478508 TI - Challenges of the 1990's. PMID- 8478507 TI - Sleep disorders and anxiety as symptom profiles of sympathoadrenal system hyperactivity in major depression. AB - Recently, it has been reported that major depression is accompanied by an increased sympathoadrenal system (SAS) activity. In order to study the psychopathological correlates of SAS activity in depression, the authors measured the 24 h urinary excretion of catecholamines (CA), i.e., noradrenaline (NE), adrenaline (E), dopamine (DA) and the NE/E metabolite 3-methoxy-4 hydroxyphenylglycol (MHPG) in 80 unipolar depressed subjects. The excretion of these indices of SAS activity have been studied in relation to the depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Depression Rating Scale (HDRS). There were significant positive correlations between the SCID item sleep disorders and the HDRS item middle insomnia, on the one hand, and NE, E and DA excretion, on the other. The MHPG excretion in 24 h urine was significantly and negatively related to somatic anxiety and hypochondriasis. It is suggested that these intertwined relationships between increased CA turnover, sleep discontinuity and anxiety may reflect the occurrence of a hyperarousal state in some major depressives that may be regarded as a coping response to various putative noxious stimuli. PMID- 8478509 TI - Economics of dentistry: practitioner income and employee wages. PMID- 8478510 TI - Update on scholarship among dental faculty. AB - A study was conducted to gather data from dental deans regarding the publication rates of faculty in dental schools. An analysis of the findings suggests that when compared with a previous study the rate of publication has increased. For tenure awardees, the number of publications has increased when the findings of the current study are compared with the original study. At all academic ranks, the publication rate has increased. The increase is more pronounced at the ranks of associate and full professor. The effect on the publication rate is the same for those schools with small numbers of advanced education programs when compared with schools that have larger numbers of advanced programs. The changing nature of dental education has resulted in an increased emphasis on scholarly activity involving a shift away from teaching and toward scholarship. This shift is evident in faculty publication rates when the findings of the two studies conducted by the authors are compared. In the future, it may be expected that dental faculty may be required to contribute to the professional literature at a rate equivalent to or greater than is required at the present time. PMID- 8478511 TI - Where we stand with AIDS. PMID- 8478512 TI - After the analysis: analyst as both old and new object. AB - In the course of followup study of satisfactorily analyzed former patients, there are observed two sets of phenomena: (1) recurrence of the analytic transference neurosis, and (2) rapid recovery from this transference neurosis. These phenomena are telescoped repetitions of the analysis and reflect the ongoing mental representation of the analyst as a displacement from the objects of the past, organized into the transference neurosis. The spontaneous and rapid recovery from the transference neurosis in followup study repeats the "cure" of the analysis and the new ongoing representation of the analyst as a nonconflicted object. This new image of the analyst is based on both the resolution of the transference neurosis and new displacements from positive experiences with significant figures from the past. PMID- 8478513 TI - The eclectic analyst, or the many roads to insight and change. AB - Common wisdom has it that psychoanalysis is composed of a number of discrete bodies of theoretical and technical thought, or "schools." I argue that psychoanalytic schools are not as different from one another as they are commonly supposed to be, particularly in matters of technique. In their daily practice, most analysts do not adhere strictly to the precepts of a specific school, even though they profess to be adherents of that school. Instead, they read widely and adopt those technical procedures and principles that fit their own personality and prove most efficacious with their patients, regardless of the school from which those ideas come. In short, they are eclectic. I present a case to illustrate this eclecticism in my own practice, discuss the widespread nature of such eclecticism among the professions in general, and briefly discuss the significance of eclecticism for psychoanalysis itself. PMID- 8478514 TI - Shall drawing become part of free association?: Proposal for a modification in psychoanalytic technique. AB - Three psychoanalytic case vignettes are presented where drawing is used beneficially as part of the free-associative process. The history of the psychoanalytic use of drawing is briefly reviewed, together with a new technical proposal regarding the role of drawing in free association. Justification for testing this modification leads to a consideration of methodological issues and the nature of free association. Possible advantages of this modification, including enhanced clinical understanding through integration of pictorial and verbal modes, and greater potential for access to the period of life where experience is more visually dominated, are considered and also discussed in relation to dual hemispheric mental organization. PMID- 8478515 TI - On reminiscences. AB - Recently, psychoanalysts have focused on narrative truth and hermeneutics with diminished attention to the role of remembering in symptom formation and treatment. This shift has tended to remove us from prior status as a motivational and cognitive science with potential for causal inferences. At the same time, psychiatry and cognitive science have moved toward a vigorous study of reminiscences and their role in pathology. Arguments for a revival of Freud's position on the central role of memory are cited. A case example is offered to show that Freud and his psychoanalytic progeny have never taken a simplistic view of archeological truth, but were among the original group to bring to light the distorting effect of mind on remembering, and actually led the way for other scientific approaches. PMID- 8478516 TI - Paranoia: a part of most analyses. AB - Paranoid defenses appear during most analyses, sometimes with great intensity, but often subtly, and require specific analytic attention. Preoedipal conflicts, inner fears around passivity, narcissistic injury and rage, and subsequent masochistic and projective defenses lie at the core of these patients' pathology. In addition, specific cognitive, object-relational, and affective distortions reflecting multiple developmental levels emerge during analysis. A case vignette is provided to demonstrate the analysis of a neurotic patient without borderline features who showed prominent paranoid formation. PMID- 8478517 TI - Useful aspects of acting out: repetition, enactment, and actualization. AB - In his seminal paper on acting out, Freud (1914) wrote: "We render the compulsion [to repeat] harmless, and indeed useful, by giving it the right to assert itself in a definite field. We admit it into the transference as a playground in which it is allowed to expand in almost complete freedom and in which it is expected to display to us everything in the way of pathogenic instincts that is hidden in the patient's mind" (p. 154). This paper reexamines the ambiguous concept of acting out as both a resistance to and a useful component of the analytic process. Current concepts of repetition in the transference, enactment, and actualization avoid the pejorative connotation of acting out and, therefore, allow for a more neutral, analytic attitude toward these inevitable and vital components of the analytic process. PMID- 8478518 TI - Therapeutic process and developmental process in the restructuring of object and self constancy. AB - This paper holds that the analytic relationship embodies both therapeutic process and developmental process, that these processes are best viewed as different and separate, and that they function in a complementary way in the revision of pathologically impaired and underdeveloped psychic structure. The focus of the paper is on the developmental formation and clinical restructuring of object and self constancy. The illustrative case material is excerpted from the case of a man who returned for additional treatment five years after the completion of an apparently successful analysis of his neurotic conflicts. PMID- 8478519 TI - Can analysts agree? The problems of consensus and the psychoanalytic mannequin: I. A proposed solution. AB - Psychoanalysis, plagued by lack of demonstrable consensus on clinical formulations, is as much endangered by overinflated agreement from stereotypical dynamic formulas: tests of psychoanalytic hypotheses derived from any such formulations may therefore rest on questionable foundations. The problems that give rise to artifactual overagreement or failure to reach agreement are here traced in earlier empirical psychoanalytic research. Review reveals that although new and inventive empirical strategies (applied in the last two decades) achieve adequate success in the area of agreement, they demonstrate little headway in ruling out that stereotypy may underlie such consensus. The present investigation offers a solution for testing agreement in complex clinical psychoanalytic propositions, in a way that sets up a "test of the mannequin": that is, whether stereotypical assumptions about the patient's dynamics are overridden (revised) by the specific character of a given patient's narrative. The mannequin concept introduces a new and epistemically crucial consideration in the making of psychodynamic formulations and is relevant to both empirically controlled and clinical contexts of observation and formulation. No psychoanalytic paradigm, whether classically ego-psychological, self-psychological, control-mastery, or object-relational, escapes this problem. PMID- 8478520 TI - Can analysts agree? The problems of consensus and the psychoanalytic mannequin: II. Empirical tests. AB - The present investigation reports on the execution of an empirical strategy for testing agreement in complex clinical psychoanalytic propositions, and for testing whether stereotypical assumptions are overridden (revised) by the specific character of the patient's narrative. The findings reveal that, in general, for the several domains of psychoanalytic formulation, psychoanalyst judges reach superior levels of ordinal agreement, and modest to good levels for agreement on magnitude. Moreover, formulations based on verbatim psychoanalytic sessions pass the "test of the mannequin" in most domains, i.e., surpass stereotypical psychoanalytic assumptions about the patient's dynamics. The mannequin concept, here operationalized, introduces a new and epistemically crucial consideration for the making of psychodynamic formulations. Other novel contributions of these studies include the development of operationalized measures of (reconstructive) historical linkage, and the introduction of magnitudinal agreement in this empirical area. PMID- 8478521 TI - What is sublimated in sublimation? AB - Sublimation has always been an elusive idea in psychoanalytic thought. This is because psychoanalysis is most systematic as a clinical psychology, while sublimation signifies an obverse of neurosogenesis. Nevertheless, the idea of sublimation remains a concern of psychoanalysis inasmuch as sublimation entails a version of socialization and cultural experience that answers to various principles of psychoanalytic theory. For reasons developed here, the creation and experience of art figure prominently in reflections on sublimation. Clinical material from the analyses of several artists is presented to demonstrate how neurosis takes a toll of sublimation and how sublimation takes a toll of the analytic process. Sublimatory experiences are then reconstructed from the devices of art. Two achievements of sublimation are especially noted: reduction of the ordinary instrumental functions of affects, and heightened consciousness of endopsychic processes. PMID- 8478522 TI - Comments on erroneous interpretations of Freud's seduction theory. AB - The seduction theory, as formulated by Freud in 1896, has been erroneously understood by many to be a statement about the frequency of sexual abuse of children, but in reality it postulates a specific etiology of adult psychopathology. Freud stated two conditions that would falsify the theory. When he discovered their existence, he was forced, very much against his preference, to abandon the theory. Later, this sequence was denied and Freud's change of theory was referred to opprobrious subjective traits, assertions made without documentation except by Masson. He maintained that he had come across a document from the pen of Ruth Mack Brunswick the alleged content of which implied grave deficits in Freud's scholarship. When it became possible to examine the original document, it was found that it does not contain anything corresponding to what Masson reported. The discrepancies between his account and Mack Brunswick's draft are presented. In the document, Mack Brunswick set forth some of the observations she had made when treating the Wolf Man in the years subsequent to the patient's first analysis, which she had reported in 1928. Her enlargement of the role of seduction in the etiology of the Wolf Man's psychopathology is discussed. PMID- 8478523 TI - A transitional phase in our understanding of the psychoanalytic process: a new look at Ferenczi and Rank. AB - In The Development of Psychoanalysis, Ferenczi and Rank (1922) demonstrate an important transitional phase in the conceptualization of the psychoanalytic process. It is not the archaic language of libidinal flow that separates their work from modern psychoanalysis, but their insistence on the ideal of the analysts's objective authority, despite the implicitly more current interpersonal and structural understandings embedded in their sound principles of character analysis. Freud's early theory presumed the possibility that an analyst could be an objective observer of forces entirely within the patient. Today's theories must account for newer intrapsychic, interpersonal, and intersubjective realities -the analyst's subjective experience as well as his observing functions. In the decade preceding the monograph, implicit developmental, structural, and object relational understandings began to emerge. A concurrent dramatic but unacknowledged change in the meaning of the terms "psychic reality" and "intrapsychic" also occurred. The controversies surrounding the monograph predicted many lines of development and dialectics for future theoretical discourse. The subjects of countertransference and empathy, almost entirely absent in the monograph, became major fields of study, and focal points for divergent schools in the new struggle to define the necessary roles of the analyst's interaction and subjective experience. PMID- 8478524 TI - Preoperative prophylactic antibiotics: brief historical note. PMID- 8478525 TI - Nosocomial invasive aspergillosis in lymphoma patients treated with bone marrow or peripheral stem cell transplants. AB - OBJECTIVES: To determine the prevalence of aspergillosis in lymphoma patients housed in a protective environment while undergoing a bone marrow transplant or peripheral stem cell transplant and its relation to lymphoma type, type of transplant, period of neutropenia, method of diagnosis, species of Aspergillus, and the use of empiric amphotericin B. DESIGN: Clinical, autopsy, and microbiology records were reviewed retrospectively to determine the presence or absence of invasive aspergillosis. All positive specimens underwent further review to determine parameters outlined above. SETTING: The review took place at the University of Nebraska Medical Center with lymphoma patients housed in the oncology/hematology special care unit, which consists of 30 single-patient rooms under positive pressure with high-efficiency particulate air filtration. PATIENTS: 417 lymphoma patients admitted to the oncology/hematology special care unit who underwent 427 courses of high-dose chemotherapy with or without total body irradiation followed by a stem cell rescue. RESULTS: Twenty-two cases (5.2%) of nosocomial invasive aspergillosis (14 caused by Aspergillus flavus, 2 by Aspergillus terreus, 2 by Aspergillus fumigatus, and 4 by characteristic histology) were diagnosed. The prevalence of disease according to transplant was 8.7% for allogeneic bone marrow transplant (2/23 treatments), 5.6% for autologous peripheral stem cell transplant (9/161), and 4.5% for autologous bone marrow transplant (11/243). Fifteen patients were presumptively diagnosed prior to death (68.2%) most commonly by histologic examination of skin biopsies. All 22 patients received amphotericin B therapy, 17 prior to aspergillosis diagnosis, and 7 (31.8%) survived. No patient with disseminated disease survived. CONCLUSIONS: Even when housing lymphoma patients undergoing myeloablative therapy in a protective environment containing high-efficiency particulate air filtration, there was a risk of developing aspergillosis. These data also showed that antemortem diagnosis with aggressive amphotericin B therapy was most effective in the management of infected lymphoma patients when engraftment occurred and the disease did not become disseminated. PMID- 8478526 TI - Installing needle disposal boxes closer to the bedside reduces needle-recapping rates in hospital units. AB - OBJECTIVE: To compare the proportion of recapped needles, an injury surrogate measure, in disposal boxes on two different types of hospital units, both before and after an intervention. DESIGN: Prospective nonrandomized intervention trial. SETTING: A major public teaching hospital. PARTICIPANTS: Specific hospital units. We selected two types of hospital units for study: the first type of hospital unit (medical-surgical ward) had existing mounted in-bathroom needle disposal boxes, and the second type of hospital unit (intensive care unit) had unmounted needle disposal boxes in the room but not necessarily near the patient's bedside. INTERVENTION: The installation, in the medical-surgical wards only, of mounted needle disposal boxes on the wall near the patient's bed. The box location in the intensive care units remained the same. In both types of unit, a new mailbox-slot disposal box (SAGE) also was substituted for the previous round-top container. RESULTS: The baseline proportion of recapped needles in the first medical surgical unit was 32.6% (+/- 3.8%) and in the second medical-surgical unit it was 27.4% (+/- 4.0%) in the bathroom needle disposal boxes, which was similar to the observed proportion (34.7 +/- 6.4%) in the intensive care unit boxes. Following the intervention, the proportion of recapped needles was significantly reduced in the disposal containers adjacent to the bedside in medical-surgical units, to 27% (a difference of 2.9 standard errors of the baseline distribution) in the first unit and 18.2% (a difference of 4.6 standard errors) in the second. In the intensive care unit, where boxes were not moved but new mailbox-types were simply substituted, no significant change was noted (36.6%, a difference of 0.59 standard errors). A statistically significant reduction was observed in the proportion of needles recapped in both wards combined following the intervention (30.2% to 26.2%, a difference of 2.9 standard errors). CONCLUSION: Environmental changes alone are an effective means of altering the risk to healthcare workers from sharp instruments. The use of needle-box counts provides a sensitive and stable instrument to measure injury surrogates and, indirectly, behavioral change in hospital workers. PMID- 8478527 TI - Physical and chemical composition of hospital waste. AB - For selecting the most efficient treatment method of hospital waste, the composition analysis is generally considered to be the fundamental information. Currently, there are few studies regarding the characteristics of hospital waste. This study evaluated the physical and elemental composition of the hospital waste at the National Taiwan University Hospital (NTUH). The results should help us design an incinerator for the treatment of infectious waste, plastic syringes, pathological waste, and kitchen waste. During the study period, the estimated daily waste generation rate at NTUH was 4,600 kg/day, which consisted of 4,100 kg/day noninfectious refuse, 340 kg/day infectious waste, 70 kg/day kitchen waste, 50 kg/day pathological waste, and 40 kg/day plastic syringes. The NTUH waste consisted of 99.02% combustible wastes and 0.97% noncombustible wastes by mass. The combustible wastes constituted paper (16.17%), textiles (9.77%), cardboard, wood, and leaves (1.12%), food waste (21.51%), and plastics (50.45%). The noncombustible waste included 0.40% metal and 0.57% glass. Furthermore, the analysis indicated that the wastes contained 38% moisture, 4% ashes, and 58% solid with an average heat value of 3,400 kcal/kg. From the elemental analysis, the dominant elements were found to be carbon (34%) and oxygen (15%). PMID- 8478528 TI - A fire on the AIDS ward. PMID- 8478529 TI - An innovative option to comply with 1992 OSHA guidelines. PMID- 8478530 TI - Malaria: protection of the international traveler. AB - Thorough counseling with emphasis on the importance of mosquito bite avoidance, as well as on compliance with prophylactic antimalarial regimens, remains an important task for the physician preparing a patient for international travel. Chloroquine continues to be the drug of choice for prophylaxis in areas not reporting chloroquine resistance. Otherwise, mefloquine is the first-line agent. Under special circumstances, alternatives to mefloquine can be employed and include doxycycline or proguanil plus chloroquine. PMID- 8478531 TI - Statistics for hospital epidemiology. PMID- 8478532 TI - Epidemiology of nosocomial ventilator-associated pneumonia. PMID- 8478533 TI - Hospital may lose federal funding for discriminating against HIV-positive healthcare worker. PMID- 8478534 TI - New TB control recommendations call for four-drug regime and HIV testing of TB patients. PMID- 8478535 TI - NIOSH to expand research on workplace transmission of infectious diseases. PMID- 8478536 TI - Nonclinical epidemiologists concerned about quality in healthcare. PMID- 8478537 TI - Cooperation needed to control TB. PMID- 8478538 TI - Responsibilities of infection control practitioners. PMID- 8478539 TI - Nosocomial infections surveillance. PMID- 8478540 TI - Selective surveillance for nosocomial infections in a Brazilian hospital. AB - OBJECTIVE: To devise a system for surveying the frequency of nosocomial infections in a tertiary care hospital in a developing country. DESIGN: Prospective selective surveillance by nurses of the charts of patients at high risk for nosocomial infections, as identified by a form completed by resident physicians. The sensitivity, specificity, and predictive value of this method of selective surveillance were compared with those for total prospective chart review by two infectious disease specialists. SETTING: A university hospital in northeastern Brazil. PATIENTS: All patients hospitalized for more than 72 hours with an identified risk factor for nosocomial infection. RESULTS: The ratio of nosocomial infections to 100 discharges was 13.4 and the incidence density was 11.2/1,000 patient days. The surveillance method demonstrated a sensitivity of 74% and a specificity of 99.7%. Positive predictive value was 93%, negative predictive value was 99%, and overall accuracy was 98%. CONCLUSIONS: This method of selective surveillance for nosocomial infections based on risk factors identified by physicians demonstrated excellent predictive value and overall accuracy and may be of use to other hospitals that lack a nursing care plan book such as the Kardex. The relative frequency of nosocomial infections significantly exceeded the rates reported from hospitals in developed countries. PMID- 8478542 TI - Validation of surgical wound surveillance. AB - OBJECTIVE: To determine the sensitivity and specificity of standard infection control surveillance techniques for the identification of surgical wound infections. DESIGN: Surveillance data collected by three infection control practitioners (ICPs) was compared to surveillance data collected simultaneously by a gold standard observer. SETTING: University-affiliated, tertiary care hospital. METHODS: Using standard infection control surveillance techniques (chart review and discussions with patients' nurses and physicians), ICPs collected surveillance data on patients on the General Surgery and Trauma Surgery Services on days 4 and 7 after surgery and then weekly for 30 days or until patients were discharged from the hospital. Simultaneously, a hospital epidemiologist collected surveillance data and examined each patient's wound daily. RESULTS: Nine hundred twenty-five surgical patients including 537 trauma cases and 388 elective general surgery cases were followed postoperatively. The ICPs identified 67 surgical wound infections, and the hospital epidemiologist identified 80 surgical wound infections for a sensitivity of 83.8% with a 95% confidence interval (CI95) of 75.7% to 91.9%. Specificity was 99.8% with a CI95 of 99% to 100%. The sensitivity was the same for trauma surgery and general surgery, but incisional wound infections were more difficult to identify than deep wound infections. During a second validation period, sensitivity was 92.3% with a CI95 of 62% to 100%. CONCLUSIONS: Standard infection control surveillance techniques have the same sensitivity for detection of surgical wound infections as they do for identification of other nosocomial infections. Accurate data on surgical wound infections can be collected without direct examination of surgical wounds. PMID- 8478541 TI - Klebsiella pneumoniae infection on a rehabilitation unit: comparison of epidemiologic typing methods. AB - OBJECTIVE: To identify factors associated with an increased occurrence of Klebsiella pneumoniae isolation in urine cultures and infected wounds on a rehabilitation unit and to compare typing methods for K pneumoniae isolates. DESIGN: Retrospective review of laboratory reports and patient records with case control study. Analysis of K pneumoniae isolates using capsular serotyping, enzyme electrophoretic typing, ribotyping, and DNA typing. SETTING: 48-bed rehabilitation unit in an 1,100-bed tertiary care teaching hospital in Winnipeg, Manitoba. RESULTS: In 1988, 20 (19%) of 106 patients admitted to the rehabilitation unit had K pneumoniae isolated from urine or wound, and in 1989 31 (28%) of 111 patients had Klebsiella isolated. Review of ward practices revealed appropriate written policies but evidence of failure in execution leading to multiple opportunities for transmission among patients. Substantial environmental contamination was not identified, although a common urine graduate may have contributed to some transmission. Individuals with K pneumoniae isolated had a significantly longer duration of stay. Many of these were spinal cord-injured patients and were maintained on intermittent catheterization. One outbreak strain was identified in epidemiologic typing. Other strains were generally identified in individuals with non-nosocomial acquisition of infection. Comparison of epidemiologic typing methods suggests ribotyping may be the optimal method for typing K pneumoniae strains. CONCLUSIONS: K pneumoniae was acquired frequently by spinal cord-injured patients with extended admissions, re-emphasizing the importance of both patients and staff following appropriate infection control practices on rehabilitation wards. Ribotyping was the optimal method for typing K pneumoniae isolates. PMID- 8478543 TI - Comparison of patient telephone survey with traditional surveillance and monthly physician questionnaires in monitoring surgical wound infections. AB - OBJECTIVE: To evaluate the utility of patient telephone surveys in further improving the detection of surgical wound infections (SWIs) postdischarge in the setting of ongoing traditional surveillance system and monthly physician surveys. DESIGN: Prospective surveillance study of randomly selected patients undergoing surgery in inpatient or outpatient settings. SETTING: Tertiary care suburban hospital. RESULTS: Five hundred one patients were randomly selected for telephone contact, of whom 189 (38%) were successfully contacted after three attempts. Eighteen (9.5%) patients reported one or more signs or symptoms of possible SWI. However, none of these patients required antibiotic therapy, was hospitalized with an SWI, or reported by his or her physician (based on the monthly questionnaire) to have had an SWI. Total time spent contacting patients was 47 hours and 48 minutes, or 15 minutes per each successful telephone contact. CONCLUSIONS: Patient telephone surveys as conducted in this study were inefficient and failed to substantially improve the rate of detection of SWIs over traditional surveillance system and monthly physician questionnaires. PMID- 8478544 TI - Urinary tract infections in long-term care facilities. PMID- 8478545 TI - A needleless intravenous system: an effective risk management strategy. PMID- 8478546 TI - Tuberculosis in the healthcare setting in the 1990s: from Bird Island to the Bronx. PMID- 8478547 TI - AHA issues revised AIDS/HIV recommendations. PMID- 8478548 TI - Court orders AIDS patient to pay exposed healthcare worker. PMID- 8478550 TI - Guidelines available for managing TB and HIV in the workplace. PMID- 8478549 TI - Glaxo, Inc., releases video on preventing occupational HIV infection in healthcare workers. PMID- 8478551 TI - New York begins 24-hour hotline for AIDS clinical drug trial information. PMID- 8478552 TI - New CDC recommendations call for voluntary testing of hospital patients. PMID- 8478553 TI - Impaired mobility: Guillain-Barre syndrome. AB - Guillain-Barre syndrome (GBS) is a complicated degenerative disorder which can be chronic or acute in nature. Its etiology is unclear although it has been associated with both cell- and humoral-mediated autoimmune mechanisms. Pathophysiologic effects of the disease include inflammation, demyelination of peripheral nerves, loss of granular bodies and degeneration of the basement membrane of the Schwann cell. This results in ascending paralysis and loss of cranial nerve function. Manifestations may be acute or chronic, and temporary or permanent, depending upon the degree of neuronal destruction. Due to the pervasive nature of GBS, nursing care is a challenge. Assessment of motor, respiratory and cardiac function is of key importance. Total care of the patient focuses on risks related to impaired mobility and ineffective airway clearance. Psychosocial care and patient education are also integral components of care. PMID- 8478554 TI - Multiple sclerosis: health-promoting behaviors of spousal caregivers. AB - This pilot study examined the relationship between health-promoting behaviors of spousal caregivers of individuals with multiple sclerosis (MS) and dependency needs of the afflicted spouses. The study sample included 20 subjects who were residing with their spouses and served as primary caregivers. The data were collected through a semistructured interview of caregiving spouses. The health promoting lifestyle profile (HPLP) was used to measure health-promoting behavior. The Index of ADL was employed to measure independence in activities of daily living (ADL). Descriptive statistics were calculated for demographic, ADL and health-promoting variables. Pearson product-moment correlations were employed to assess the relationship between the care recipient dependency needs and the health-promoting behavior of the caregiving spouse. Findings revealed a significant inverse relationship between level of recipient dependency and health promoting behavior of the caregiver (r = -.394, p < .04). Further examination of health behaviors revealed that caregiving wives reported higher total frequency of health-promoting behaviors than did their husband counterparts. Additional analyses revealed subjects scored highest on the self-actualization dimension and lowest on the exercise dimension of the HPLP scale. PMID- 8478555 TI - Responsible dissemination of scholarly work. PMID- 8478556 TI - Development of printed teaching materials for neuroscience patients. AB - Neuroscience nurses are challenged by the current climate of cost containment and the nursing shortage to continue to provide quality patient education. One strategy for meeting this challenge is to follow the process outlined in this overview for the development and use of printed materials. PMID- 8478557 TI - The changing health care system: neuroscience nursing practice in the 1990s. AB - Radical changes in the health care system, including the paradigm shift from an acute to chronic illness model, and advances in managing major neuroscience patient populations are redefining neuroscience nursing practice in the 1990s. For example, advances in management mean that many more neurotrauma patients and patients with cerebrovascular disorders survive. Once stabilized, illness may become chronic and require long-term management. There are also promising developments in managing major neurological diseases. The decade of the 90s will require more collaboration, new practice models and a greater focus on rehabilitation. Research and education must support practice in reshaping neuroscience nursing. PMID- 8478558 TI - Needs of family members of critically ill patients with and without acute brain injury. AB - A comparative descriptive study was implemented to identify and compare the personal needs of family members of critically ill patients with and without acute brain injury. The study was, in part, a replication of Mathis's study which used Molter's Critical Care Family Needs Inventory (CCFNI) to identify differences in the degree of importance of the perceived personal needs between family members of critically ill patients with and without acute brain injury. Fourteen relatives of critically ill patients completed and mailed a questionnaire adapted from the CCFNI. Results indicated a difference in the degree of importance of the perceived personal needs between the family members of critically ill patients without acute brain injury and family members of critically ill patients with acute brain injury at the 0.001 level of significance (Chi square = 17.70, critical value = 16.27, df = 3). Similarities in the rank ordering of the need statements were found between the two groups in this study and in comparison to the groups in Mathis's study. Family members indicated that most needs were met (78.5%) and nurses and doctors were identified as meeting the majority of these needs (> 80%). Ongoing research is necessary to determine what the needs of the relatives are in order to most effectively use the energies of health care professionals in providing patient care. PMID- 8478559 TI - Head-injured adults: recommendations for endotracheal suctioning. AB - Endotracheal suctioning (ETS) is a conventional nursing intervention used to decrease pulmonary complications in the critically ill patient. ETS provides a particular dilemma for the head-injured patient because it increases intracranial pressure and may put the patient at increased risk for intracranial hypertension and cerebral ischemia. Research in endotracheal suctioning targets understanding the ETS response in the severely head-injured patient. This article reviews the major research focused on suctioning the head-injured patient. The guidelines for practice based on this research include preoxygenating patients prior to suctioning, limiting suction duration to 10 seconds, limiting suction passes to 1 2 per procedure, using hyperventilation with caution, not rotating the head, keeping negative suction pressure under 120 mm Hg, and not using suction catheters with outer to inner diameter ratios greater than .50. PMID- 8478560 TI - Hyponatremia after aneurysmal subarachnoid hemorrhage. AB - Hyponatremia frequently complicates the clinical course for patients with aneurysmal subarachnoid hemorrhage (SAH). Although commonly attributed to the syndrome of inappropriate antidiuretic hormone (SIADH), emerging evidence suggests a range of pathological conditions may produce the abnormality. Effective management requires an approach to data collection which avoids suppositions about etiology, as incorrect assumptions may result in selection of interventions leading to further clinical deterioration. Adherence to comprehensive monitoring and management protocols ensures rapid detection and efficient management of this common problem after SAH. PMID- 8478561 TI - [Effects of oxygenation and/or SOD on addition to St. Thomas' Hospital cardioplegic solution]. AB - The effects of oxygenation (95% O2 + 5% CO2) and/or SOD (400 mg/l) on addition to St. Thomas' Hospital cardioplegic solution were examined by hemodynamic, cytochemical and biophysical assessments in the isolated working rat heart subjected to hypothermic ischemic arrest (22 degrees C in temperature, 180 min in ischemic time) with multidose cardioplegic infusion. According to the feature of used cardioplegic solution, thirty-two rats were divided into four groups (8 animals per group): That is, Group I; O2 (+) SOD (+), Group II; O2 (-) SOD (+), Group III; O2 (+) SOD (-), Group IV (control); O2 (-), SOD (-). Aortic flow (AF) recovery, expressed as a percent of pre-arrest AF, was 76.7 +/- 11.7% in Group I, 66.9 +/- 7.1% in Group II, 73.9 +/- 11.6% in Group III and 57.7 +/- 12.9% in Group IV (mean +/- SD). Differences in recovery between Group I vs III and Group III vs IV approached statistically significance (respectively, p < 0.01, p < 0.05). The birefringence ratio (ATP value/air value) of the biopsy specimen was 2.49 +/- 0.53 in Group I, 1.96 +/- 0.44 in Group II, 2.04 +/- 0.29 in Group III and 1.65 +/- 0.39 in Group IV (mean +/- SD). Difference between Group I and Group IV indicated statistically significance (p < 0.05). The birefringence ratio (X) had good correlation with the AF recovery ratio (Y): Y = 29.7 + 19.1X (R = 0.74). No statistical difference was seen from cytochemical assessment (myosin ATPase stain) in four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478562 TI - [A new skeletal muscle powered ventricle (SMPV) designed to work under physiologic preload]. AB - To maximize pumping function the SMPV has been highly preloaded (over 30 mmHg); but the effects of pump size and configuration on the required preload have never been determined. A new double barrel dual chamber single layered (DCSL) SMPV having two SL small pumps in parallel was compared with a single chamber double layered small pump (SCDL). Stroke volume (SV) and stroke work (SW) were determined in acutely constructed SMPV using mongrel dog untrained latissimus dorsi: 10 DCSL and 12 SCDL. Under physiologic afterload (120 mmHg) and preload (15 mmHg), the DCSL displayed a significantly (p < 0.05) larger SV (9.9 +/- 1.2 ml) and SW (0.84 +/- 0.15 x 10(6) ergs) than the SCDL pumps (SV = 6.9 +/- 0.6 ml, and SW = 0.55 +/- 0.07 x 10(6) ergs). The DCSL pumps, requiring less muscle mass for its construction, indicated better performance under physiologic pre and afterload conditions than SCDL pumps. PMID- 8478563 TI - [Surgical results in diabetics undergoing coronary artery bypass grafting]. AB - Diabetes mellitus is a well-known risk factor in the patients undergoing coronary artery bypass grafting (CABG) and with increasing frequency diabetic patients are referred for CABG. From the fact that the arteriosclerosis is more diffuse and advanced in patients with diabetes, the presence of the diabetic state might be expected to be at risk for CABG. We retrospectively evaluated the surgical results in 91 patients with diabetes mellitus operated on from January, 1985, to June, 1991, compared with a control group of 339 patients during the same period. Compared with nondiabetic patients, diabetic patients had more extensive coronary artery disease and, therefore, received the more number of grafts per patient. However, no difference was noted in the incidence of operative mortality, morbidity and postoperative complication. The incidence of postoperative sternotomy infection was slightly higher, if not statistically significant, in the diabetic patients. Our study demonstrates that patients with diabetes mellitus can be operated on relatively safely. PMID- 8478564 TI - [A basic study on bradycardiac dysrhythmias following atrial surgery]. AB - Various dysrhythmias often developing atrial surgery can be lethal, although the precise mechanism remains unknown. An experimental study was conducted to elucidate the influence of internodal tract injury and sinoatrial node (SAN) artery blockade on bradycardiac arrhythmias, using 40 adult mongrel dogs. Changes in rhythm, SAN tissue flow rate, SAN function and His bundle electrocardiogram were evaluated in those with complete division of the internodal tract (INT) and/or artery blockade under cardiopulmonary bypass. The results were as follows: 1) Junctional rhythm (JR) or ectopic atrial rhythm (ER) occurred in 87.5% of those subjected to anterior INT (AINT) division+SAN artery blockade, whereas such arrhythmias developed in none of those with division of any single INT alone, and appeared in only 18% of those with SAN artery blockade alone; 2) The SAN tissue flow rate was reduced to 29 +/- 17% of the control level by AINT division+SAN artery blockade, while it was reduced to only 91 +/- 16%, 84 +/- 12% and 90 +/- 18% by division of AINT, MINT and PINT, respectively, and 55 +/- 16% by SAN artery blockade (The former was significantly lower than the latter two (p < 0.01)); 3) None of those with the SAN tissue flow rate of less than 10 Laser Doppler Flowmeter unit (LDF unit) by laser Doppler flowmeter output were capable of maintaining sinus rhythm (SR) with its minimum requirement that was assumed to be more than 10 LDF unit; 4) Immediately before shifting to JR, corrected sinus recovery time (CSRT) was elongated, indicating a hypofunction of the SAN; 5) The A-H interval was more significantly prolonged by AINT division than by either of the other two divisions (p < 0.01). Division of the AINT brought about prolongation of the A-H interval, and AINT division+SAN artery blockade caused a marked SAN hypofunction. It was inferred that preservation of both the AINT and the SAN artery should be of vital importance in preventing surgical bradycardiac arrhythmias. PMID- 8478565 TI - [Extravascular lung water in patients after cardiac surgery]. AB - Extravascular lung water (EVLW) measured by a double indicator dilution method using thermal-dye indicator was evaluated in 204 patients after cardiac surgery during last 7 years. The measurement of EVLW was done at 2, 4, 8, 24 and 48 hours after extracorporeal circulation (ECC), EVLW showed no significant change except transient decrease at 4 hours after ECC, average of that was 7.62 +/- 3.58 ml/kg, EVLW of group I (MVR) and group III (AVR + MVR) were significantly higher than those of group II (AVR), group IV (noncyanotic congenital heart disease) and group V (A-C bypass). EVLW of 7 patients with postoperative pulmonary edema was 14.47 +/- 4.44 ml/kg, and that was significantly higher than those of others (7.54 +/- 3.06 ml/kg). EVLW of the patients using bubble oxygenator (8.60 +/- 3.90 ml/kg) was significantly higher than those of membrane oxygenator (7.15 +/- 3.40 ml/kg). Postoperative EVLW correlated with mean pulmonary artery pressure (mPAP), mean left atrial pressure (LAP) and microvascular hydrostatic pressure (PMV), and showed inverse correlation with cardiac index (CI). But there was no correlation of EVLW with duration of ECC. In the preoperative parameter, EVLW correlated with age, mPAP, mean pulmonary wedge pressure (mPAWP), PMV, serum BUN and serum creatinine, and showed inverse correlation with CI, %VC, FEV%, PSP test and creatinine clearance. We concluded that the patients with mitral valve disease who have high mPAP and LAP, respiratory and renal dysfunction and old aged preoperatively showed upward trend of EVLW. In perioperative management, care must be taken in such patients and membrane oxygenator was thought useful for prevention of pulmonary edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478566 TI - [Evaluation of the right ventricular function in postoperative esophageal cancer patients]. AB - We evaluated the right ventricular function in pre- and post-operative esophageal cancer patients who had no complications after surgery by measurement of cardiopulmonary hemodynamics, right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) using Swan-Ganz catheter and the thermodilution technique. The measurement of RVEF, RVEDVI and other cardiopulmonary hemodynamics were performed from the preoperative day to the 3rd postoperative day. The values of RVEF were stable about 40% from preoperative day to 3rd. RVEDVI was varied at 93.6 +/- 26.3 ml/m2 (preoperative day), 83.6 +/- 15.0 ml/m2 (after surgery), 70.2 +/- 10.6 mg/m2 (morning of the 1st POD), 95.6 +/ 19.4 ml/m2 (evening of the 1st POD), 103.2 +/- 17.9 m/lm2 (morning of the 2nd POD), 1108.3 +/- 14.2 ml/m2 (evening of the 2nd POD) and 112.4 +/- 31.0 ml/m2 (morning of the 3rd POD). The values of RVEDVI on the morning of the 1st POD were statistically lower than those at other times (p < 0.05). The values of RVEDVI were not correlated with mean pulmonary arterial pressure and pulmonary arteriolar resistance which were the afterload of the right ventricle. These data suggest that the right ventricular function of the patients who underwent esophagectomy with no complication does not change and that the changes of RVEDVI are influenced by the preload of the right ventricle. PMID- 8478567 TI - [Exercise test to predict postoperative complications in patients with impairment of pulmonary function]. AB - We studied the prediction of postoperative complications in patients whose predicted postoperative FEV1.0% and/or %VC were below fifty. Preoperative exercise tests were performed in 88 cases mainly old patients of age or with impaired pulmonary function; 57 were lobectomies, 10 were bilobectomies and 21 were pneumonectomies. Predicted postoperative FEV1.0% and/or %VC were below fifty in 29 cases consisting of 12 lobectomies, one bilobectomy and 16 pneumonectomies. Among these 29 patients, thirteen suffered postoperative complications (A group) and sixteen did not (B group). All five cases of operative death (death within 30 days after operation) were included in the A group. The prediction of postoperative complications in cases of which pred. postope, FEV1.0% and %VC were fifty or over (C group) was also studied. The results were as follows; (1) The percentage of complications among A and B groups was higher than that among C group but no statistical difference could be found. (2) In the A group, the number of pred. postope. FEV1.0% and/or %VC had little correlation to complications. (3) Statistical differences between A and B group were found in submax VO2 (p < 0.05), VO2/VE at AT (p < 0.001) and VCO2/VE at submaximal exercise (p < 0.001). (4) Cardiac output ratio of maximal exercise to rest had marked correlation to complications (p < 0.001) in C group but had no correlation in the A and B groups. (5) The three items of A and B groups, submax VO2 < 500 ml/min/m2, VO2/VE at AT < 40 ml/l and submax VCO2/VE < 25 ml/l, showed high correlation to operative death (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478568 TI - [Surgical repair in hearts with univentricular atrioventricular connection and subaortic stenosis]. AB - Between 1986 and 1990, fourteen patients with univentricular atrioventricular connection and subaortic stenosis underwent surgical treatment. The patients consisted of 7 cases of double inlet left ventricle, 4 with double inlet right ventricle, 3 with tricuspid atresia. The palliative operation was performed in 6 infants ranging in age from 17 days to 6 months. Four patients with mild subaortic stenosis underwent pulmonary artery banding, in two patients this was combined with repair of coarctation of the aorta. Two patients with severe subaortic stenosis underwent the Norwood operation. There were no operative deaths. One of two patients who underwent the Fontan operation 2 years after the Norwood operation died later. The definitive operation was performed in 8 children ranging in age from 4 to 11 years. Five of these 8 patients had previous pulmonary artery banding. Five children with double inlet left ventricle underwent septation combined with enlargement of bulboventricular foramen. Postoperatively all remained in sinus rhythm and had no pressure gradient between Aorta and left ventricle. A Fontan operation combined with a Damus operation was performed in 2 children, 1 of double inlet right ventricle and 1 of tricuspid atresia. In both cases, postoperative angiogram showed no pulmonary incompetence. One patient underwent enlargement of bulboventricular foramen after a Fontan operation. All survived later. Young infants and neonates with severe subaortic stenosis can survive by the Norwood operation. Infants with mild subaortic stenosis, although can survive by pulmonary artery banding, should be closely followed for the development of subaortic stenosis. For relief of subaortic stenosis, enlargement of bulboventricular foramen may be effective in septation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478569 TI - [Surgical treatment with aortic valve homograft harvested from heart transplant recipients or donors]. AB - From March 1988 to November 1991, 24 patients underwent aortic valve replacement or aortic root replacement with an aortic homograft harvested from a heart transplant recipient or donor that was not suitable for heart transplantation. Those patients were followed from 2 to 34 months (mean 12.6 months). The mean age was 44 years (range 19 to 77 years). The main lesion was aortic stenosis in 8 patients, aortic regurgitation in eight, mixed lesion in eight, annulo-aortic ectasia in two, active prosthetic valve endocarditis in two, and recurrent LVOTO in one. Cardiac status before operation was NYHA class II in one patient, III in nineteen, IV in four. Aortic valve replacement was performed in 17 patients, and aortic root replacement in seven. There was no early or late death. No structural deterioration was found. Surgical technical error resulted in moderate aortic regurgitation in one patient and mild paravalvular leak in another patient immediately after operation. All patients except one were not given anticoagulants postoperatively, but the entire group was free from thromboembolism. All patients returned to NYHA class I. Most homografts in this series were cryopreserved without antibiotic sterilization immediately after harvest, but homograft valve endocarditis did not occur. The results in this series suggested that homografts from heart transplant recipients or donors were encouraging, but more long-term follow-up was required to be determined whether homografts from heart transplant recipients without antibiotic sterilization were superior to homografts prepared in ordinary manner. PMID- 8478570 TI - [Immunocytochemical investigations of occluded saphenous vein grafts]. AB - Occluded saphenous vein aorto-coronary bypass grafts were investigated using two types of monoclonal antibodies, specific to either the muscle actin (HHF 35) or the macrophage (HAM 56). The early post operative occlusions of saphenous vein grafts were associated with the deposition of mural thrombi with little intimal proliferation. The late occlusions of saphenous vein grafts were associated with intimal fibrous proliferation without mural thrombus formation. Proliferated smooth muscle cells were a major constituent of intimal fibrous proliferation in both early and late occluded grafts. Macrophages were not detected in both groups. The proliferation of smooth muscle cells in the intima may play a role in the development of late occlusion, rather than the organizational process of accumulated mural thrombi. PMID- 8478571 TI - [Clinical application of recombinant human SOD for the protection of ischemia reperfusion injury during open heart surgery]. AB - We have applied recombinant human superoxide dismutase (RH-SOD) to prevent ischemia reperfusion injury in the patients who received open heart surgery. Twenty-four patients were divided into 2 groups; group A had no treatment as control and group B received bolus injection of RH-SOD (35,000 IU/kg) into cardiopulmonary bypass 5 minutes before reperfusion. Arterial and coronary sinus blood was collected to measure chemiluminescence (ChL) value, SOD activity, lactate and pyruvate level, and several parameters of myocardial oxygen metabolism after reperfusion. Arterio-venous difference of ChL value showed the tendency of less ChL generation of the heart in group B compared with those in group A. But no other parameters showed significant difference between the two groups. Our data suggested that this way of the administration of RH-SOD failed to improve the myocardial protection during open heart surgery. Further investigation, such as dose response study, might be required to determine whether RH-SOD possess beneficial effects or not in the clinical setting. PMID- 8478572 TI - [Flow characteristics and responses to vasoactive drugs in canine gastroepiploic artery]. AB - We studied flow characteristics and response to norepinephrine, Chlorpromazine and gastrin in 22 canine gastroepiploic artery (GEA) recirculation model. The GEA flow was obtained by a drip for a minute, opening the end of pedicle GEA. Furthermore, aortic flow and celiac arterial flow were measured by magnetic flow probe. The administration of chlorpromazine, vagostigumine, and gastrin induced a increase in both celiac arterial flow and pedicle GEA graft flow. Especially, the administration of gastrin induced significant increase in GEA flow and celiac arterial flow. Furthermore, adding norepinephrine step-wisely, the GEA flow increased remarkably, in spite of decrease of celiac arterial flow. This response was caused from difference in vascular resistance among celiac arterial branches. Therefore, the pedicle GEA graft has homogenous response as same as intact GEA that perfuses stomach, because its flow was affected by adrenergic and parasympathetic agent, alpha-blocker and gastric hormone. PMID- 8478573 TI - [Cardioprotective effect of cromakalim, a K+ channel opener, on isolated globally ischemic and reperfused rat hearts]. AB - Examination was made of cardioprotective effect related to the ATP-sensitive K+ (KATP) channel on isolated globally ischemic reperfused rat hearts using cromakalim, a putative ATP-sensitive K+ channel opener. The hearts were subjected to 20 min Langendorff perfusion with Krebs Henseleit Bicarbonate Buffer (KHBB) (70 cmH2O, 37 degrees C), followed by 30 min ischemia at 36 degrees C, and 30 min reperfusion with KHBB, with (cromakalim group) or without (control group) pretreatment by 10 microM cromakalim added to KHBB for 5 min prior to ischemia. Before ischemia, no significant change in heart rate (HR), left ventricular developed pressure (LVDP) or coronary flow (CF) by 10 microM cromakalim could be detected. The two groups were the same in CF during reperfusion, but recovery of HR and LVDP significantly improved in the cromakalim group. Creatine kinase (CK) leakage in the cromakalim group was significantly less than in the control group during reperfusion. Cromakalim is thus shown to reduce the myocardial injury during ischemia and reperfusion. Intracellular Ca2+ content of the cromakalim group appeared lower than that of the control group at 30 min of reperfusion. At 5-30 min of reperfusion, in the cromakalim group, intracellular Ca2+ storage was prevented, leading to a good recovery of cardiac function, while in the control group, intracellular Ca2+ increased and recovery of cardiac function was poor. After pretreatment with 10 microM cromakalim, intracellular K+ content of the cromakalim group was significantly lower than in the control group before ischemia. At 5 min of reperfusion, intracellular K+ content of the cromakalim group was slightly less than that of the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478574 TI - [Autotransplantation as optimal technique for recurrent malignant myxoma of left ventricle]. AB - Application of autotransplantation for left ventricular recurrent malignant tumor which was considered to be originating from the posterior leaflet of mitral valve was presented. A patient was 29 year-old-female and underwent the resection of tumor. The tumor was resected en bloc with the mitral valve, and its histology was myxoma. But she was required reoperation two times because of the recurrence of the tumor unfortunately. The tumor was ultimately diagnosed as the myxofibrosarcoma with chondroid differentiation. At the time of the third surgery, the heart transplantation was thought to be only treatment for radicality. While sounding American counterparts on the possibility of the heart transplantation, her condition took a sudden turn for the worse. An autotransplantation technique was applied for the resection of the tumor emergently. As a result, it was impossible to completely resect the tumor because of severe invasion to the left ventricle, and the patient died suddenly on the 75th day after the operation due to fetal arrhythmia. Through this case, heart transplantation should be considered for such a case, but autotransplantation technique allowed to be a life-prolonging in this case. We believe that this technique which will be obtained the excellent operative field could be used for repair of complex cardiac anomalies and rupture of left ventricle and so on. PMID- 8478575 TI - [A case of an intra-pericardial bronchogenic cyst requiring an emergency operation]. AB - The patient was a 36-year-old male, who complained of anterior chest pain and dyspnea. A chest X-ray showed a cardiac enlargement and widened tracheal carina. A cardiac echography showed an intra-pericardial simple cyst which was fixed and did not move with cardiac motion. CT showed a cyst, measuring to 10 cm between the left atrium and vertebra. An angiography revealed that the left atrium and right main pulmonary artery were compressed in the anterior direction. Because his symptoms deteriorated suddenly, an emergency operation was performed. The intrapericardium was explored through the right postero-lateral thoracotomy, and the cyst was resected. A microscopic examination revealed that the cystic wall was lined with ciliated columnar epithelium and contained cartilage and bronchial gland. Review of the literatures indicated that the most of the intra-pericardial bronchogenic cysts were revealed as cardiac enlargement by chest X-ray film, and that the cyst compressing the atrium or main pulmonary artery should be resected without delay, because of a risk of sudden death or cardiac failure. PMID- 8478576 TI - [A case of solitary plasmacytoma that originated in a rib]. AB - A 52-year-old woman was admitted to our hospital with the chief complaint of left anterior chest pain. A chest X-ray showed a tumor shadow in the left 4th rib. No abnormalities were detected in peripheral blood and aspirated bone marrow samples. The tumor was surgically resected with the involved bone, the intercostal muscle and the parietal pleura. The resected specimen contained a 3 x 6 x 3 cm lesion, and histological investigation of the tumor revealed a plasmacytoma of the rib. It relapsed as a multiple myeloma within two months after surgery. Chemotherapy was administered and the bone lesions were observed to disappear. We believe that the best way to treat solitary plasmacytoma is to first resect the solitary tumor, and then to add cobalt irradiation and chemotherapy after surgery. PMID- 8478577 TI - [A case of thymic cyst & thymolipoma with ocular myasthenia gravis]. AB - A 65-year-old woman with ocular myasthenia gravis (MG) and thymic tumor underwent expanded thymectomy. Histologically the tumor was thymic cyst and thymolipoma. To our knowledge, there has been no case reported in medical literatures, which is thymic cyst & thymolipoma with ocular MG. This case suggests some effect of steroid therapy. PMID- 8478578 TI - [A case of isolated congenital left ventricular diverticulum]. AB - Isolated congenital diverticulum of the left ventricle is a rare malformation. A 2-year-old boy was admitted to our hospital for evaluation of heart murmur. The echocardiogram and MRI showed an extra cavity communicating with the left ventricle. The diagnosis was made by LV angiography. He was diagnosed as having congenital isolated diverticulum of the left ventricle without other cardiac anomalies. He received resection of the diverticulum under cardiopulmonary bypass. Histological examination showed a fibrous diverticulum. Postoperative clinical course was uneventful. We can expect good prognosis after resection of the congenital diverticulum of the left ventricle, if necessary under cardiopulmonary bypass. PMID- 8478579 TI - [A case report of coronary sinus atrial septal defect]. AB - We experienced an uncommon case of coronary sinus atrial septal defect, which was not associated with a left superior vena cava (LSVC). A 29-year-old woman, who experienced fatigue during moderate exercises, was found to have the atrial septal defect located in the lower part of the septum by echocardiography preoperatively. On operation, the coronary sinus ASD was diagnosed. The ostium of coronary sinus was located in the left atrium. This type is classified as partially unroofed coronary sinus without LSVC. Our case, in the absence of the LSVC, was repaired by simple closure of the coronary sinus ASD, so the coronary veins drained into the left atrium. Postoperative course was uneventful. PMID- 8478580 TI - [Report of a case of the anomalous origin of the right coronary artery from the pulmonary artery with atrial fibrillation and bradycardia]. AB - A 62-year-old man who was referred to implantation of pacemaker on account of severe bradycardia revealed anomalous origin of the right coronary artery from the pulmonary artery on aortography. The aortic root cineangiogram demonstrated single left coronary artery arising from the aorta with retrograde filling of the right coronary artery (RCA) which drained into the main pulmonary artery. Chest X ray revealed marked cardiomegaly and treadmill exercise test shows positive at stage 2 of the Bruce protocol. Operation was performed under cardiopulmonary bypass. Although we tried to transplant the RCA to the aorta, the arterial wall was very fragile and could't bear arterial pressure. Therefore the RCA was ligated at its origin and disconnected from the pulmonary artery. Post operative course was uncomplicated and the patient was discharged without any symptoms. PMID- 8478581 TI - [A case report of successfully corrected 26 days old infant of tetralogy of Fallot with absent pulmonary valve]. AB - A female infant weighing 2.4 kg had respiratory distress at birth. She became dyspneic and hypercapnic and required intubation with assisted ventilation 11 days after birth. Because cardiac failure and respiratory failure did not improve, she underwent total correction at 26 days old, which consisted of VSD closure, right ventricular outflow tract reconstruction with valved porcine pericardial roll (VPR) and plication of both pulmonary arteries. She was weaned from the ventilator 11 days after operation and discharged at 12 weeks of age. One year later, reoperation was successfully performed for the replacement of the stenotic VPR with a transannular patch. PMID- 8478582 TI - [Extirpation of intra-atrial tumor thrombus of renal cell carcinoma by means of extracorporeal circulation--report of a case]. AB - We report a case of renal cell carcinoma with a tumor thrombus extending into the right atrium, which was successfully removed with the use of extracorporeal circulation. A 68-year-old male presented with a one month history of abdominal distension. CT-scanning, selective renal angiography, vena cavography and echocardiography revealed a left renal tumor with a tumor thrombus extending into the right atrium through the inferior vena cava. Left nephrectomy and removal of the intra-atrial tumor thrombus were performed using extracorporeal circulation. Preoperative laboratory results showed elevation of the total bilirubin (17.0 mg/dl) due to congestion of the liver which was caused by obstruction of hepatic vein with the tumor thrombus. Postoperatively, the total bilirubin gradually decreased to 11.9 mg/dl on the third day, but increased to 22.2 mg/dl on the 9th day. So plasma exchange was performed on the 10th, 11th and 12th days, and the total bilirubin decreased to the normal range. The patient was discharged on the 50th day. For renal cell carcinoma with a tumor thrombus extending into the right atrium, effectiveness of operation using extracorporeal circulation and subsequent prognosis are discussed. PMID- 8478583 TI - [Two cases of intrapulmonary teratoma]. AB - We encountered two unusual cases of intrapulmonary teratoma, one in a 31-year-old female and the other in a 15-year-old female. The chief complaint of both patients was fever, and in both a consolidation was detected in the left upper lobe using routine radiography. We performed left upper lobectomy for the former patient and segmentectomy of the left lingual segment for the latter. Neither tumor communicated with the mediastinum. Histological examination revealed a pulmonary teratoma containing no thymic tissue in both. Intrapulmonary teratoma has been reported to be extremely rare, and only 27 cases including these two have been reported in the literature. PMID- 8478584 TI - [A case of myocardial revascularization in a patient after renal transplantation]. AB - A 46-year-old woman after renal transplantation 10 years ago underwent CABG using the right internal thoracic artery to LAD, the left internal thoracic artery to Circumflex and the right gastroepiploic artery to RCA, with the diagnosis of unstable angina (triple vessels disease) after failed PTCA. The postoperative course has been uneventful. To our knowledge, this is the first case who underwent GABG after renal transplantation in Japan. PMID- 8478585 TI - [A combined operation of aortic valve replacement and bullectomy for aortic valve stenosis and giant bulla]. AB - A 61-year-old male with aortic valve stenosis and giant bulla, whose respiratory function was very poor, successfully underwent a combined operation of aortic valve replacement and bullectomy. Firstly aortic valve replacement was performed under cardio-pulmonary bypass, and after coming off bypass, giant bulla was resected via median sternotomy. Postoperative respiratory function was improved remarkably (VC: per-op 1.89 l, post-op 2.53 l, FEV1.0: pre-op 0.74 l, post-op 1.13 l) and also his clinical symptom improved from Hugh-Jones IV. to I. postoperatively. PMID- 8478586 TI - [A case of acute postinfarction mitral regurgitation and cardiogenic shock caused by a total rupture of the papillary muscle]. AB - We report a case of mitral regurgitation caused by a total rupture of the posterior papillary muscle that had occurred after acute myocardial infarction. A 72-year-old woman was transferred to our hospital for cardiogenic shock. Echocardiogram revealed massive mitral regurgitation and prolapse of posterior mitral leaflet presumably due to a rupture of a papillary muscle. Cardiac catheterization demonstrated a total occlusion in the segment 2 of the right coronary artery. She had developed progressively increasing heart failure even though the patient had received a successful PTCA for a total occlusion of the right coronary artery. She underwent an emergency mitral valve replacement with preservation of the posterior leaflet using a SJM prosthetic valve. Intraoperative findings were confirmative of total rupture of the posterior papillary muscle. A postoperative course was uneventful. This case is the seventh case which has been reported as the successful operation of a total rupture of the papillary muscle in Japan. PMID- 8478587 TI - [Emergency operation for complete papillary muscle rupture after myocardial infarction--a case report of 81-year-old patient]. AB - Mitral regurgitation due to complete rupture of the papillary muscles after myocardial infarction has a very poor prognosis, even if diagnosed and operated on at an early phase. Recently, we performed an emergency operation for mitral regurgitation due to complete papillary muscle rupture after myocardial infarction in an 81-year-old patient. This is probably the oldest case in Japan. Operation revealed complete rupture of the posterior papillary muscle, and valve replacement with a Carpentier-Edwards bioprosthesis was performed. PMID- 8478588 TI - [A case report--successful surgical treatment of prosthetic aortic valve detachment with enlargement of sinuses of Valsalva caused by the recurrence of aortitis]. AB - A successful operation on a 49-year-old female with aortitis syndrome associated with prosthetic aortic valve detachment was reported. Aortic valve replacement using SJM 25A had been performed for aortic regurgitation caused by aortitis. Though her C-reactive protein (CRP) was kept between (+/-) and (2+) with prednisolone administered, general fatigue suddenly appeared 4 years after the first operation. The blood sedimentation rate was 65 mm/30 min and CRP was (4+), and the echocardiography showed abnormal movement of the prosthetic valve with perivalvular leakage on admission. Aortography showed the valve detachment and abnormal movement due to enlargement of sinuses of Valsalva, one of which was transformed as a diverticulum and projected into Left ventricular cavity with moderate leakage. After the inflammation was well controlled, she was operated upon. Dilatation of sinuses, perforation of intima around the prosthetic valve were recognized as left ventricular-aortic discontinuity, but ascending aorta was not enlarged. So the prosthetic valve was suspended below coronary ostia with transmural mattress sutures from right atrium. Postoperative course was uneventful. The postoperative aortography revealed only trivial perivalvular leakage without abnormal movement of the valve. This was a rare case of the valve detachment in the aortitis patient. PMID- 8478589 TI - Histidine-rich glycoprotein: an abundant plasma protein in search of a function. PMID- 8478590 TI - Pathogenetic mechanisms in cystic fibrosis lung disease: a paradigm for inflammatory airways disease. PMID- 8478591 TI - Academic medicine: the social consciousness of the profession. PMID- 8478592 TI - The genetics of the Gilles de la Tourette syndrome: a review. AB - The Gilles de la Tourette syndrome (GTS) is a hereditary, neuropsychiatric neurobehavioral disorder with childhood onset that is characterized by motor and vocal tics that may vary from relatively mild to very severe. The exact pathogenesis is still unknown. Following anecdotal reports of familial occurrence, systematic family studies have been carried out since 1980 to establish the mode of inheritance and ultimately to map and clone the susceptibility gene(s). Currently, as a result of combined North American, English, and Dutch studies, the most accepted genetic model is an autosomal dominant pattern of inheritance with incomplete penetrance and a variable expression. The objective of linkage studies is to "link" a particular DNA sequence (with known chromosomal localization) with the disease in all affected family members. Essential for these gene mapping studies is a clear and rigorous definition of the phenotype. Such studies are vastly more difficult if the disease phenotype is ambiguous, proper subject assignment being clouded by incomplete penetrance, cases mild enough to escape detection, or genetically unrelated but highly associated traits. Indeed, because of just these features, the initial optimism about the "well-defined and easy-to-objectivate" phenotype of GTS has gradually been tempered. The tics vary in frequency and severity, are frequently suppressed during examination, or might go unnoticed when associated behavioral symptoms like disturbed impulse control, obsessive-compulsive disorder and attention deficit disorder with hyperkinesia (among others) dominate the clinical picture. Whether these associated behavioral symptoms are a part of the phenotype remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478593 TI - Familial association of high levels of histidine-rich glycoprotein and plasminogen activator inhibitor-1 with venous thromboembolism. AB - High levels of histidine-rich glycoprotein (HRGP) and plasminogen activator inhibitor-1 (PAI-1) have been claimed to contribute to the hypofibrinolytic state observed in patients with venous thrombosis. These abnormalities were detected, respectively, in eight and 10 members of a family from which four of seven members with both abnormalities had venous thromboembolism. Binding of tissue plasminogen activator (t-PA) by PAI-1 may induce hypofibrinolysis. To determine whether plasminogen binding by HRGP may influence plasminogen activation, we studied the fibrinolytic activity of members of this family cohort with a system that detects modifications in plasmin generation by proteins interfering with the binding of plasminogen to fibrin. Plasminogen activation was performed by adding plasma to fibrin surfaces to which t-PA had been previously bound in the presence of 40 mg/ml bovine serum albumin and 20 mumol/L of the lysine analog trans-4 (aminomethyl)-cyclohexane carboxylic acid to prevent nonspecific binding and thereby the inhibitory effect of elevated PAI-1 levels. The generation of plasmin as a function of time was detected (1) by photometric analysis with a chromogenic substrate highly selective for plasmin and (2) by measuring the binding and activation of plasminogen at the fibrin surface with radiolabeled plasminogen. The amount of plasmin generated by plasma from patients having high levels of HRGP (160% to 280%) was similar to that of a control group having normal levels of HRGP (100% +/- 22%). Similar results were obtained with a plasma artificially depleted in HRGP and supplemented with various amounts of this protein. No correlation between HRGP level and t-PA-mediated plasminogen activation was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478594 TI - Effect of chronic potassium depletion on muscle bioenergetics in rats. AB - To test the hypothesis of muscle bioenergetic impairment in potassium depletion, chronic potassium-depleted rats and pair-fed control rats were studied with phosphorus 31 nuclear magnetic resonance measurements of leg muscle intracellular pH, phosphocreatine, inorganic phosphate, and adenosine triphosphate at rest and during maximal nontetanic stimulation, 48 hours after a swimming test. The potassium-depleted rats exhibited a significant hypokalemia, a metabolic extracellular alkalosis, and an intracellular acidosis. Their physical endurance was markedly reduced, and they displayed higher plasma creatine kinase levels than the control group. However, the phosphocreatine/inorganic phosphate ratio, which is a measure of the energy reserve of the cell, was similar in both groups at rest and during electrical stimulation and subsequent recovery. Resting muscle glycogen and relative intracellular acidification during stimulation did not differ in the two groups, arguing against an impairment of anaerobic metabolism in potassium depletion. These results indicate that the energy availability of muscle cell is unchanged during potassium deficiency. PMID- 8478595 TI - Staphylococcus aureus binding to cardiac endothelial cells is partly mediated by a 130 kilodalton glycoprotein. AB - Binding of Staphylococcus aureus to vascular endothelial cells may be an initiating event in the pathogenesis of endovascular infection, particularly infective endocarditis. In this study a competition assay between labeled and unlabeled bacteria was used to identify potential S. aureus-binding determinants on the surface of cultured porcine aortic valve endothelial cells. Concanavalin A inhibited 30% to 40% of the specific binding of S. aureus to membrane-associated components. Concanavalin A affinity chromatography of radiolabeled cell-surface proteins, followed by isolation of S. aureus-binding proteins, identified a 130,000-molecular-weight cell surface protein that may function as an endothelial cell S. aureus receptor. These data suggest that specific binding of S. aureus to cardiac valve endothelial cells is mediated in part by a 130 kd mannose containing glycoprotein. PMID- 8478596 TI - Biochemical and immunochemical localization of GTP-binding proteins in the rat ileal enterocyte. AB - This study characterizes the distribution of various guanosine triphosphate binding proteins (G proteins) in rat intestinal epithelial membranes. Enriched basolateral membranes were prepared from isolated enterocytes through differential density centrifugation; apical membranes were prepared with a chaotropic agent. Enrichment and purity of the membrane fractions were assessed by various biochemical markers. G proteins were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after adenosine diphosphate ribosylation in the presence of pertussis or cholera toxins. Western blotting was performed with the use of highly specific antibodies against the following subunits: alpha Gs, alpha G1(1 or 2), alpha G 1(3), alpha Go, alpha Gz, and beta subunits. Adenosine diphosphate ribosylation catalyzed by cholera toxins revealed two major substrates of molecular weights 47 and 43 kd in only the crude and basolateral fractions. The reaction catalyzed by pertussis toxin revealed a 41 kd substrate in the crude and basolateral fractions and a 40 kd substrate in the apical fraction. Immunoblotting confirmed the presence of alpha Gs, alpha G1(1 or 2), and alpha G1(3) but failed to identify alpha Go or alpha Gz subunits in the basolateral fraction; none of these subunits were identified in the apical fraction. Beta subunits were identified in both apical and basolateral fractions. These findings suggest selective sorting of the G proteins to regional domains in the plasma membrane of intestinal epithelial cells. The presence of previously unidentified G proteins is also suggested. PMID- 8478597 TI - Lactic acid changes during and after hypothermic cardiopulmonary bypass in infants. AB - Infants undergoing open-heart surgery with hypothermic cardiopulmonary bypass experience markedly elevated lactate and glucose levels. Reports in infants less than 10 kg show the elevated lactate to be progressive during the operative period. The pathogenesis of the hyperglycemia is not clear but may be caused by excess glucose administration, inadequate insulin response, or glucose regulatory hormone levels of glucagon, cortisol, and growth hormone. The purpose of this study is to confirm these findings and to investigate their pathogenesis. Serial blood samples were taken preoperatively, intraoperatively, and postoperatively during hypothermic cardiopulmonary bypass in nine infants of less than 10 kg. Samples were analyzed for levels of lactate, glucose, and regulatory hormones insulin, growth hormone, glucagon, and cortisol. Our study did not show a progressive accumulation of lactate. The elevated lactate level appears to come from the pump prime solution. The hyperglycemia is also from the pump prime solution, and there do not appear to be elevated levels of regulatory hormones intraoperatively. Insulin response during hypothermia is blunted; however, on rewarming the patient in the immediate postoperative period, a brisk insulin response is seen. The changes in levels of lactate and glucose and the regulatory hormones return to baseline at 24 hours with no further significant changes in the next 48 hours. PMID- 8478598 TI - Comparative study of the adhesion of sickle cells and malarial-parasitized red cells to cultured endothelium. AB - Increased adhesion of red cells to vascular endothelium has been implicated in the pathogenesis of falciparum malaria and sickle cell disease. We have carried out a comparative study of the adhesiveness of normal (AA), sickle trait (AS), and homozygous sickle (SS) red cells, with and without parasitization by Plasmodium falciparum, with an in vitro flow system. Adhesion of nonparasitized red cells to cultured human umbilical vein endothelial cells (either glutaraldehyde fixed or untreated) was strongly dependent on the wall shear stress. Many AA and SS cells adhered at low stress (0.02 Pa), but far fewer did so when the stress was increased to a physiologic level (0.1 Pa). Compared with AA cells, SS adhered in greater number (about threefold) and required greater stress (about two-fold) for their subsequent removal. In contrast, the efficiency of adhesion of AA cells parasitized by Plasmodium falciparum was essentially constant up to 0.1 Pa, where it was about 1000 times greater than the efficiency for nonparasitized cells. The stress required to remove parasitized cells was about 6 times that for controls. When parasites were grown in SS cells, fewer cells adhered than when parasites were grown in AA cells. However, the adhesion of malarial-parasitised AS cells was only slightly less than that of parasitized AA cells, so that modulation of adhesion is unlikely to underlie the protective effect of sickle gene in malaria. Adhesion of red cells to endothelium may promote blockage of microvessels, and the interaction of parasitized cells appears strong enough to directly cause ischemic complications in falciparum malaria. PMID- 8478599 TI - Relevance of findings may be limited to rat model. PMID- 8478600 TI - Glycogen loss in rat muscles during locomotion on different inclines. AB - Running downhill causes structural damage in deep slow-twitch extensor muscles of the limbs. Both mechanical and metabolic hypotheses have been proposed to explain the damage. The purpose of this study was to use measurements of glycogen loss in the muscles and metabolic rates of rats running on the level and up and down 16 degrees inclines at 26 m min-1 to try to distinguish between these hypotheses. Glycogen loss in the soleus and medial head to the triceps brachii muscles during running on the three inclines was proportional to whole-animal oxygen consumption, indicating that there were no unusual metabolic demands on these muscles during the downhill exercise. The minimum area of these muscles showing glycogen loss was smaller during downhill than during uphill running. Average forces in the muscles are similar during locomotion on different inclines at the same speed, suggesting that stresses in the active motor units were greater during downhill running. Thus, the results are more consistent with a mechanical than with a metabolic etiology for the muscle injury resulting from downhill running. PMID- 8478601 TI - Contractile properties of the striated adductor muscle in the bay scallop Argopecten irradians at several temperatures. AB - The isometric and isotonic contractile properties of the cross-striated adductor muscle of the bay scallop (Argopecten irradians) were measured in vitro at 10, 15 and 20 degrees C. The length at which twitch force was maximal as a function of the closed length in situ (L0/Lcl) averaged 1.38 +/- 0.01 (mean +/- S.E.M.) at 10 degrees C. This length is very close to the typical length at maximum gape during natural swimming at this temperature. Passive force was very low over the range of lengths measured here; at L0, passive force averaged approximately 0.08 N cm 2, or only 0.5% of the corresponding peak twitch force. The mean peak isometric twitch force (Ptw,max) at 10 degrees C was 21.43 +/- 0.68 N cm-2 (S.E.M.), and the ratio of peak twitch force to tetanic force (Ptw,max/P0) averaged 0.89 +/- 0.01. Temperature did not affect either twitch force (Ptw), once fatigue was taken into account, or Ptw,max/P0. In contrast, the time-related properties of twitch contractions (latent period, tL; time to peak tension, tPtw; and time from peak tension to half-relaxation, t50%R) were positively modified by temperature at all temperatures measured (Q10 > 1.8). All three properties were more temperature-sensitive over the range 10-15 degrees C than over the range 15-20 degrees C. The force-velocity relationships of the striated adductor muscle were fitted to the hyperbolic-linear (HYP-LIN) equation. The force-velocity curves of the striated adductor muscle of the scallop were strongly influenced by temperature. Maximal velocity at zero force (Vmax), and therefore maximal power output, increased significantly with temperature. The Q10 over the temperature range 10-15 degrees C (1.42) was significantly lower than that over the range 15 20 degrees C (2.41). The shape of the force-velocity relationship, assessed through comparisons of the power ratio (Wmax/VmaxP0), was not influenced by temperature. PMID- 8478602 TI - Acetate, butyrate and proline uptake in the caecum and colon of prairie voles (Microtus ochrogaster). AB - We have measured unidirectional uptake (not transmural flux) of acetate, butyrate and proline by everted sleeves of intact tissue from the jejunum, caecum, proximal colon and distal colon of prairie voles (Microtus ochrogaster). There was active (i.e. Na(+)-dependent) transport of L-proline in the jejunum, but we found no evidence for it in any region of the hindgut (i.e. the caecum, proximal colon and distal colon). Uptake of acetate was carrier-mediated in all three regions of the hindgut, but the Jmax and apparent Km (< or = 1.5 mmol l-1) were low, and uptake was primarily passive over the concentration range 10-50 mmol l 1, which spanned measured acetate levels in the caecum and proximal colon. At 100 mmol l-1, acetate uptake (nmol min-1 cm-2) was higher (P < 0.001) in distal colon (359 +/- 33) than in the proximal colon (225 +/- 17) and caecum (150 +/- 5) (mean +/- S.E., N = 8). Uptakes summed over the length of each region were also higher (P < 0.001) in the distal colon at 100 mmol l-1, but not at low concentrations (0.1 mmol l-1). Uptakes normalized to diffusion coefficients were higher for butyrate than acetate and were lowest for L-glucose (which is absorbed passively via an aqueous pathway) in all regions, indicating that uptake of the short-chain fatty acids involves solubilization in the lipid bilayer of the apical membrane. The short-chain fatty acids absorbed from the hindgut of the vole were equivalent to 22% of standard metabolic rate or 15% of resting (but fed) metabolic rate. PMID- 8478603 TI - Lateral line stimuli can override vision to determine sunfish strike trajectory. PMID- 8478604 TI - Development of connections by axons growing through injured spinal cord of neonatal opossum in culture. AB - The ability of neurites to grow through a lesion and form synaptic connections has been analyzed in a developing mammalian spinal cord in vitro. After isolation of the entire central nervous system (CNS) of the newly born South American opossum (Monodelphis domestica) the spinal cord was crushed. Outgrowth through and beyond the lesion was observed in living preparations for 2-5 days by staining axons with carbocyanine dyes. The structure of the acute crush and the growing neurites was examined by light and electron microscopy in tissue fixed immediately after the crush had been made. All axons had been severed and the site was filled with debris and amorphous vesicular structures. By 3 days after injury, numerous labelled neurites had grown into the lesion; by 4 days, many had extended several millimetres beyond it. At this time normal axonal profiles were apparent in electron micrographs of the crush site. Although fewer axons grew across the lesion than had been severed by the crush, the amplitudes of compound action potential volleys conducted across the crush in injured preparations were comparable with those recorded from uninjured spinal cords. Physiological experiments made with raised concentrations of extracellular magnesium in the culture fluid indicated that growing axons had formed synaptic connections. Thus, delayed major peaks of the response were abolished while the small component corresponding to through conduction remained unaffected by magnesium. These experiments demonstrate the development of synaptic interactions by the growing neurites and confirm the far greater powers of repair in neonatal mammals compared to adults. They set the stage for comparing molecular mechanisms involved in development and regeneration of the mammalian CNS. PMID- 8478605 TI - Suppression of cell motility and metastasis by transfection with human motility related protein (MRP-1/CD9) DNA. AB - Previously we showed that motility-related protein (MRP-1) is an antigen recognized by monoclonal antibody (mAb) M31-15 inhibiting cell motility and that the sequence of MRP-1 coincides with that of CD9. In the present study, plasmid was constructed in which human MRP-1/CD9 cDNA is expressed under the control of the Abelson murine leukemia virus promoter sequence. The expression plasmid for MRP-1/CD9 was introduced into Chinese hamster ovary cells, human lung adenocarcinoma cell line MAC10 (MRP-1 positive), and human myeloma cell line ARH77 (MRP-1 negative). All of the MRP-1/CD9 (over)expressing clones obtained from these transfected cells showed suppressed cell motility (penetration and phagokinetic track assays) depending on the degree of expression of MRP-1/CD9. Overexpression of MRP-1/CD9 by MAC10 cells resulted in the suppression of cell motility (maximally 73%) associated with considerable inhibition of the cell growth (maximally 48%). However, the inhibition of the growth of MAC10 cells by mAb M31-15 was < 17% at an antibody concentration of 1-5 micrograms/ml, which inhibits cell motility by > 90%. These results suggest that MRP-1/CD9 directly regulates cell motility and may also affect cell growth. Effects on metastasis by the expression of MRP-1 CD9 were investigated with mouse melanoma BL6 cells BALB/c nu/nu mouse system. Metastatic potential of all transformants expressing MRP-1/CD9 was lower than that of parent BL6 cells. PMID- 8478606 TI - Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo. AB - Poly- and oligoclonal T cell stimuli like anti-CD3 epsilon monoclonal antibody or Staphylococcus aureus enterotoxin B (SEB), injected at doses that per se are not lethal, provoke acute death within less than 24 h, provided that endogenous glucocorticoids (GC) are depleted by adrenalectomy or by injection of saturating amounts of the GC receptor antagonist RU-38486 (mifepristone). Pharmacological doses of the GC agonist dexamethasone (DEX) alter the in vivo response of splenic V beta 8+ T cells to SEB, thus impeding the expansion of such cells and causing their rapid (3 d) clonal deletion. In contrast, coadministration of RU-38486 counteracts a SEB-induced early (12 h) reduction of V beta 8+CD4+ and V beta 8+CD8+ spleen cells. In vivo T cell stimulation by injection of bacterial superantigen induces a rapid (peak at 90-120 min) increase in corticosterone serum levels, suggesting that endogenous GC might control early T cell activation. Accordingly, kinetic studies revealed that RU-38486 has to be administered within 2 h after superantigen administration to exert its lethal effect. Similarly, exogenous GC must be injected during this critical phase (2 h) to rescue animals from acute death induced by coinjection of SEB and D galactosamine (GalN). Adrenalectomy, injection of RU-38486 and priming with GalN per se provoke the programmed death of peripheral CD4+ and CD8+ T cells. Thus, three manipulations that sensitize mice for the lethal effect of T cell stimulation also exert a proapoptotic effect on peripheral T cells. In synthesis, endogenous and exogenous GC regulate T cell responses and determine the propensity of peripheral T cells to undergo apoptosis. PMID- 8478607 TI - Differential T cell receptor photoaffinity labeling among H-2Kd restricted cytotoxic T lymphocyte clones specific for a photoreactive peptide derivative. Labeling of the alpha-chain correlates with J alpha segment usage. AB - Using a direct binding assay based on photoaffinity labeling, we studied the interaction of T cell receptor (TCR) with a Kd-bound photoreactive peptide derivative on living cells. The Kd-restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) was reacted NH2-terminally with biotin and at the TCR contact residue Lys259 with photoreactive iodo, 4-azido salicylic acid (IASA) to make biotin-YIPSAEK(IASA)I. Cytotoxic T lymphocyte (CTL) clones derived from mice immunized with this derivative recognized this conjugate, but not a related one lacking the IASA group nor the parental PbCS peptide. The clones were Kd restricted. Recognition experiments with variant conjugates, lacking substituents from IASA, revealed a diverse fine specificity pattern and indicated that this group interacted directly with the TCR. The TCR of four clones could be photoaffinity labeled by biotin-YIPSAEK(125IASA)I. This labeling was dependent on the conjugates binding to the Kd molecule and was selective for the TCR alpha (2 clones) or beta chain (1 clone), or was common for both chains (1 clone). TCR sequence analysis showed a preferential usage of J alpha TA28 containing alpha chains that were paired with V beta 1 expressing beta chains. The TCR that were photoaffinity labeled at the alpha chain expressed these J alpha and V beta segments. The tryptophan encoded by the J alpha TA28 segment is rarely found in other J alpha segments. Moreover, we show that the IASA group interacts preferentially with tryptophan in aqueous solution. We thus propose that for these CTL clones, labeling of the alpha chain occurs via the J alpha-encoded tryptophan residue. PMID- 8478608 TI - Malaria circumsporozoite protein binds to heparan sulfate proteoglycans associated with the surface membrane of hepatocytes. AB - During feeding by infected mosquitoes, malaria sporozoites are injected into the host's bloodstream and enter hepatocytes within minutes. The remarkable target cell specificity of this parasite may be explained by the presence of receptors for the region II-plus of the circumsporozoite protein (CS) on the basolateral domain of the plasma membrane of hepatocytes. We have now identified these receptors as heparan sulfate proteoglycans (HSPG). The binding of CS to the receptors is abolished by heparitinase treatment, indicating that the recognition of region II-plus is via the glycosaminoglycan chains. We have purified and partially characterized the CS-binding HSPGs from HepG2 cells. They have a molecular weight of 400,000-700,000, are tightly associated with the plasma membrane, and are released from the cell surface by very mild trypsinization, a property which the CS receptors share with the syndecan family of proteoglycans. PMID- 8478609 TI - Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo. AB - In the rat, mesenteric lymphadenectomy allows collection of dendritic cells (DC) derived from the small intestine after cannulation of the thoracic duct. We prepared rats this way and administered antigens by oral feeding or intraintestinal injection. DC enriched from the thoracic duct lymph collected over the first 24 h from these animals are able to stimulate sensitized T cells in vitro and to prime popliteal lymph node CD4+ T cells after footpad injection, while B and T cells from the same thoracic duct lymph are inert in priming. 500 or less DC pulsed in vitro with antigen can prime T cells in vivo, whereas 100 times more B cells or macrophages pulsed in vitro are quite inert. 1 mg of ovalbumin administered orally is sufficient to load DC for in vivo priming of T cells. Antigen could not be detected directly in DC but was present in macrophages in the lamina propria. Direct presentation of antigen by DC to T cells was demonstrated by injecting F1 recipients with parental DC and showing restriction of T cell sensitization to the major histocompatibility complex of the injected DC. Antigen-bearing DC do not induce a detectable primary antibody response but a small secondary antibody response can be detected after a boosting injection. These results show that acquisition of antigens by DC in the intestine is very similar to what occurs in vitro or in other tissues, suggesting that there may be no special difference in antigen handling at mucosal surfaces. One implication of these results is that hypotheses designed to explain oral tolerance must take into account the presence of immunostimulatory, antigen bearing DC in animals that have received oral antigens. PMID- 8478610 TI - Regulatory role of OX22high T cells in mercury-induced autoimmunity in the brown Norway rat. AB - The monoclonal antibody OX22 defines a functional split within CD4+ T cells in the rat, with OX22high cells mainly producing interleukin 2 (IL-2) and interferon gamma and responsible for delayed-type hypersensitivity responses, and OX22low cells mainly producing IL-4 and -5 and responsible for providing B cell help. There are reciprocal interactions between OX22high and OX22low cells, and it has been suggested that the OX22low subset has a role in the prevention of autoimmunity. We have used OX22 in vivo to define the role of these subsets in mercuric chloride-induced autoimmunity in the Brown Norway rat. In this model, there is polyclonal B cell activation and animals develop widespread tissue injury. Treatment of thymectomized animals with OX22 led to a profound reduction in the number of OX22high T cells in the peripheral blood. OX22-treated animals consistently developed more severe tissue injury than controls given an irrelevant antibody of the same isotype. Control animals pretreated with broad spectrum antimicrobial drugs showed milder tissue injury, but this protective effect of antimicrobials was lost in OX22-treated animals. Transfer of naive T cells to OX22-treated animals provided protection, but if T cells were depleted in vitro of OX22high cells before transfer, this effect was lost. These data provide evidence for a protective immunoregulatory role for OX22high T cells in mercuric chloride-induced autoimmunity. PMID- 8478611 TI - Restricted kappa chain expression in early ontogeny: biased utilization of V kappa exons and preferential V kappa-J kappa recombinations. AB - To determine the extent of kappa chain diversity in the preimmune repertoire early in development, kappa cDNA libraries were analyzed from 15-d old fetal omentum, 18-d-old fetal liver, and 3-wk old bone marrow. An anchored polymerase chain reaction approach was used to avoid bias for particular V kappa families. From the sequence analysis of 27 bone marrow clones, 10 different families and 20 unique V kappa genes were identified. In contrast, the V kappa expression in the fetus is highly restricted and clearly differs from the broader distribution see in 3-wk-old bone marrow. Although several V kappa families were represented in the fetal library including V kappa 9, V kappa 10, V kappa 4,5, V kappa 8, and V kappa 1, one or two members of individual families were observed repeatedly. The fetal liver and omentum libraries were found to be largely overlapping. Given the V kappa families/exons identified in the fetal sequences, the mechanism of kappa rearrangements in the early repertoire appears to occur predominantly by inversion. Importantly, the fetal repertoire was further restricted by dominant V kappa-J kappa combinations such as V kappa 4,5-J kappa 5, V kappa 9-J kappa 4, and V kappa 10-J kappa 1. Since in some cases independent rearrangements could be established, the results indicate a bias for particular V kappa-J kappa joins. The results also suggest that clonal expansion/selection in the fetal repertoire takes place after light chain rearrangement as opposed to at the pre-B cell level in the bone marrow. The restriction observed in kappa light chain expression together with known restrictions in gene usage and junctional diversity at the heavy chain level indicate a remarkably conserved fetal repertoire. PMID- 8478612 TI - Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. AB - Only a fraction (12%) of 268 "autoreactive" T cell clones derived from lupus prone mice can selectively induce the production of pathogenic anti-DNA autoantibodies in vitro and accelerate the development of lupus nephritis when transferred in vivo. The CDR3 loops of T cell receptor beta chains expressed by these pathogenic T helper (Th) clones contain a recurrent motif of anionic residues suggesting that they are selected by autoantigens with cationic residues. Herein, we found that approximately 50% of these pathogenic Th clones were specific for nucleosomal antigens, but none of them responded to cationic idiopeptides shared by variable regions of pathogenic anti-DNA autoantibodies. Nucleosomes did not stimulate the T cells as a nonspecific mitogen or superantigen. Only the pathogenic Th cells of lupus responded to nucleosomal antigens that were processed and presented via the major histocompatibility class II pathway. Although the presentation of purified mononucleosomes to the Th clones could be blocked by inhibitors of endosomal proteases, neither of the two components of the nucleosomes--free DNA or histones by themselves--could stimulate the Th clones. Thus critical peptide epitopes for the Th cells were probably protected during uptake and processing of the nucleosome particle as a whole. The nucleosome-specific Th clones preferentially augmented the production of IgG autoantibodies to histone-DNA complex in vitro. In vivo, nucleosome specific, CD4+ T cells were not detectable in normal mice, but they were found in the spleens of lupus-prone mice as early as 1 mo of age, long before other autoimmune manifestations. Immunization of young, preautoimmune lupus mice with nucleosomes augmented the production of autoantibodies and markedly accelerated the development of severe glomerulonephritis. Previously, crude preparations containing nucleosomes were shown by others to have polyclonal mitogenic activity for B cells from normal as well as lupus mice. Identification here of pure mononucleosome as a lupus-specific immunogen for the Th cells that selectively help the pathogenic anti-DNA autoantibody producing B cells of lupus could lead to the design of specific therapy against this pathogenic autoimmune response. PMID- 8478613 TI - Extinction of the tumor necrosis factor locus, and of genes encoding the lipopolysaccharide signaling pathway. AB - The tumor necrosis factor (TNF-alpha or TNF) gene is activated by both lipopolysaccharide (LPS) and cycloheximide in RAW 264.7 macrophages, whereas neither stimulus activates the gene in 3T3 fibroblasts. Moreover, the pattern of CG methylation within the TNF gene is readily distinguishable in DNA derived from cells of these two types. These findings would suggest that the TNF gene has been rendered inaccessible to transcription in the 3T3 cell environment. When RAW 264.7 cells are fused with 3T3 cells, an immortal pentaploid hybrid results. In the hybrid cell, all three TNF genes contributed by the RAW 264.7 cell parent become highly methylated according to the pattern observed in the 3T3 cell parent. Permanently transfected chloramphenicol acetyl transferase (CAT) reporter constructs, bearing 2.2 kb of upstream sequence (including the entire TNF promoter and 5'-untranslated region [UTR]) as well as 1.0 kb of downstream sequence (including the entire TNF 3'-UTR and termination sequence), are accessible in both RAW 264.7 cells and 3T3 cells, but are silenced in transition from the RAW 264.7 cell to the hybrid cell environment. Moreover, the endotoxin signaling pathway is abrogated, as assessed by transient transfection of hybrid cells with LPS-responsive CAT reporter constructs. It would therefore appear that the fusion of 3T3 cells and RAW 264.7 cells activates a system that silences the TNF gene, as well as the LPS signaling pathway. This system may operate to determine TNF gene accessibility and LPS responsiveness in the course of cell differentiation. The DNA sequences targeted within the TNF gene are included in the CAT reporter construct; therefore, the silencing element has been circumscribed to a region of DNA 3.2 kb in length. PMID- 8478614 TI - Enhancement of experimental metastasis by tumor necrosis factor. AB - The influence of endogenous and exogenous tumor necrosis factor (TNF) on metastasis was investigated in an experimental fibrosarcoma metastasis model. A single intraperitoneal injection of recombinant human (rh) TNF or recombinant mouse (rm) TNF into mice 5 h before intravenous inoculation of methylcholanthrene induced fibrosarcoma cells (CFS1) induced a significant enhancement of the number of metastases in the lung. Dose responses of rmTNF and rhTNF demonstrated a stronger metastasis-augmenting effect by rmTNF compared with rhTNF. This effect was time dependent, as administration of rmTNF 5 h before or 1 h but not 24 h after tumor cell inoculation caused an increase of tumor cell colony formation on the lung surface, suggesting an influence of TNF on the vascular adhesion and diapedesis of tumor cells. Since tumor-bearing mice showed an enhanced ability to produce TNF after endotoxin injection compared to control mice, tumor-bearing mice were treated with anti-mTNF antibodies. Neutralization of endogenous tumor induced TNF led to a significant decrease of the number of pulmonary metastases. Histological analysis of micrometastases in the lung on day 5 by silver staining of proteins associated with nucleolar organizer regions revealed more metastatic foci and augmented proliferative activity of the tumor cells after rmTNF pretreatment of mice. However, no direct effect of rmTNF on the proliferation rate of tumor cells was seen in vitro. These findings suggest that low doses of endogenous TNF or administered TNF during cytokine therapy might enhance the metastatic potential of circulating tumor cells. PMID- 8478615 TI - Selective immunosuppression by administration of major histocompatibility complex class II-binding peptides. II. Preventive inhibition of primary and secondary in vivo antibody responses. AB - The self-mouse lysozyme peptide corresponding to residues 46-62 (ML46-62) binds to the major histocompatibility complex (MHC) class II molecules I-A(k) and it selectively inhibits, when coinjected with antigen, priming of I-A(k)-restricted, antigen-specific T cells. We demonstrate that administration of ML46-62 also inhibits in vivo antibody responses induced by I-A(k)-restricted T helper cells. ML46-62 is able to prevent the primary anti-hen egg white lysozyme (HEL) antibody response induced by the entire HEL molecule in B10.A(4R) mice, expressing only I A(k) molecules, but not in mice of H-2d haplotype. ML46-62 also strongly decreases, in B10.A(4R) mice, the antibody response to ribonuclease A, a protein antigen unrelated to the MHC blocker, indicating that MHC blockade is the mechanism leading to inhibition of antibody response. This is further supported by the concomitant decrease, in vivo, of complex formation between immunodominant HEL peptides and I-A(k) molecules, preventing I-A(k)-restricted T cell induction. Administration of ML46-62 after antigen priming does not affect ongoing antibody responses, as expected from MHC blockade. A single injection of ML46-62 at the time of protein antigen priming precludes not only the primary, but also the secondary antibody response to a subsequent challenge with soluble protein, even when the challenge is performed several months after priming. Coinjection of antigen and MHC antagonist inhibits production of all antibody isotypes equally well, suggesting that MHC class II blockade affects both Th1- and Th2-type T helper cells. Therefore, these results indicate that administration of MHC class II-binding peptides can efficiently and selectively prevent the induction of T cell-dependent primary and secondary in vivo antibody responses by blocking antigen presentation to class II-restricted T helper cells. PMID- 8478616 TI - Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture. AB - We have used an in vitro system to study the effects of major histocompatibility complex class I binding peptides on thymic development. Fetal thymus lobes from mice deficient in the class I light chain (beta 2 microglobulin or beta 2 M-/-) were cultured for 10 d in vitro, during which time T cell precursors develop into mature T cells. In these organ cultures, as in the adult or neonatal beta 2 M-/- thymus, CD8+ mature T cells did not develop, demonstrating that the mature T cells seen during early murine thymic development are the result of the positive selection process. To these cultures we added various class I binding peptides with or without a source of exogenous beta 2M. CD8+ T cells developed to various degrees only in the presence of beta 2M and peptides. Using peptide mixtures of differing complexity, we showed that the efficiency of this process is dependent more on peptide complexity than on peptide concentration. These data argue for a specific role for peptides in the process of positive selection. Furthermore, this culture system should be useful in identifying peptides that can promote positive selection of cells expressing a specific T cell receptor (TCR) in TCR transgenic mice. PMID- 8478617 TI - Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. AB - The transmembrane receptor for immunoglobulin G immune complexes on natural killer (NK) cells and macrophages, Fc gamma RIIIA (CD16), mediates cellular activation through a tyrosine kinase-dependent pathway. We show that Fc gamma RIII crosslinking results in activation of the src-related kinase p56lck in NK cells and demonstrate a physical association of p56lck with Fc gamma RIIIA in immunoprecipitates from NK cells obtained using anti-Fc gamma RIII antibodies or immune complexes. Our studies show that the zeta chain, the signal transducing subunit of Fc gamma RIIIA and of T cell receptor, associates with p56lck and, in NK cells, is a substrate for this kinase. Such direct association of p56lck with the zeta subunit as confirmed by demonstrating the interaction in heterologous cells transfected with cDNA expressing p56lck and zeta. Our findings demonstrate both functional and physical association of p56lck with Fc gamma RIIIA, through direct interaction of the kinase with the zeta and/or the gamma signal transducer subunits of the receptor. These data suggest a possible mechanism by which activation via Fc gamma RIIIA occurs. PMID- 8478618 TI - Bacterial superantigens mediate T cell deletions in the mouse severe combined immunodeficiency-human liver/thymus model. AB - The ability to analyze T cell receptor (TCR) thymic repertoire shaping in humans by self and foreign ligands is hampered by the lack of suitable models. We recently documented that the mouse severe combined immunodeficiency (SCID)-human fetal liver/thymus model recapitulates the TCR V beta gene repertoire of human thymocytes. Here, we show that an exogenous superantigen, staphylococcal enterotoxin B, administered to such mice induces clonal deletions in both CD4+8- and CD8+4- cells involving the same human V beta clones that are selected in vitro by this toxin. This model, therefore, may allow comprehensive studies into the effects of microbial and other agents on human T cell thymic selection processes in a biologically relevant setting. PMID- 8478619 TI - Oligoclonal expansion of major histocompatibility complex class I-restricted cytolytic T lymphocytes during a primary immune response in vivo: direct monitoring by flow cytometry and polymerase chain reaction. AB - Previous T cell receptor (TCR) sequence analysis of a panel of 23 H-2Kd restricted cytotoxic T lymphocyte (CTL) clones recognizing the decapeptide HLA CW3 170-179 revealed a striking conservation of TCR structure, in that all clones examined used V beta 10 and J alpha pHDS58 segments. We show here that the primary response in vivo after intraperitoneal injection of DBA/2 mice with HLA CW3 expressing transfectants of syngeneic P815 (H-2d) tumor cells is characterized by a dramatic expansion of CD8+ V beta 10+ CTL in the peritoneal cavity and draining (mesenteric) lymph node, as well as in peripheral blood. Additional analysis of TCR on HLA-CW3 immune populations by flow cytometry and polymerase chain reaction further indicates that the vast majority of responding CD8+ cells express restricted V alpha domains, a dominant J alpha segment (pHDS58), and a conserved CDR3 length for both alpha and beta chains. This novel system provides a unique opportunity to directly monitor an oligoclonal primary antigen specific immune response in vivo at the single cell level independently of functional assays. PMID- 8478620 TI - Prevention of autoimmune diabetes in non-obese diabetic mice by treatment with a class II major histocompatibility complex-blocking peptide. AB - The role of antigen presentation as a possible mechanism underlying major histocompatibility complex (MHC) association of autoimmune disease has been studied in non-obese diabetic (NOD) mice. By screening for inhibition of antigen presentation to NOD T cell hybridoma, we have selected a synthetic peptide, yTYTVHAAHAYTYt (small letters denote D amino acids), that efficiently blocks antigen presentation by the NOD class II MHC molecule A alpha g7A beta g7 (Ag7) in vitro. The inhibition is MHC selective, in that it does not affect antigen presentation by the E(d) and E(k) molecules, and has only a marginal effect on presentation by the A(d) molecule. This peptide also inhibits the priming for Ag7 restricted T cell responses in vivo, and prevents the spontaneous development of diabetes in female NOD mice, when administered chronically from 3 wk of age on. Chronic treatment with a control peptide, KMKMVHAAHAKMKM, that fails to bind to Ag7 has no effect on the disease. These data indicate that antigen presentation by the Ag7 molecule plays a pivotal role in the induction of autoimmune diabetes. Furthermore, the results demonstrate that interference with antigen presentation by a class II molecule can prevent the onset of spontaneous autoimmune disease associated with the same molecule. PMID- 8478621 TI - Enhanced susceptibility of blood monocytes from patients with pulmonary tuberculosis to productive infection with human immunodeficiency virus type 1. AB - Blood monocytes from patients with active pulmonary tuberculosis and age-matched healthy purified protein derivative-reactive donors were infected with human immunodeficiency virus type 1 (HIV-1)JR-FL in vitro to assess their susceptibility to productive infection by HIV-1. HIV-1 p24 levels (enzyme-linked immunosorbent assay) in supernatants of infected cells from patients with tuberculosis, albeit variable, were significantly higher at days 10-20 of culture; the maximum levels of p24 antigen were greater in supernatants of HIV-1 infected monocytes from patients than maximum levels for controls (p < 0.05). The maximum increment in p24 levels for patients also exceeded that for controls (p < 0.05). Entry of HIV-1 and/or initiation of reverse transcription, measured by polymerase chain reaction using HIV-1 R/U5 primer pairs, was variable and low in infected monocytes from both patients and controls, and did not correlate with HIV-1 p24 levels. The frequency of infected cells as assessed by endpoint dilution viral cultures was similar for both groups. Therefore, blood monocytes from patients with active tuberculosis can develop a highly productive infection with HIV-1 that does not appear to be due to enhanced HIV entry or higher frequency of infected cells. The enhanced susceptibility may result directly from activation of monocytes by exposure to Mycobacterium tuberculosis and its products in situ. PMID- 8478622 TI - Clonal anergy blocks in vivo growth of mature T cells and can be reversed in the absence of antigen. AB - Experiments in various models have indicated that immunological tolerance can result from the physical elimination (deletion) of reactive lymphocytes as well as from anergy. We have previously reported that mature CD4-CD8+ T cells when confronted with their antigen can proliferate extensively but are finally eliminated or become intrinsically anergic such that remaining cells are refractory to stimulation by any T cell receptor ligands, even in the presence of exogenous interleukin 2. Here we show that in vivo the anergy can be reversed in the absence of antigen, such that the cells are then able to proliferate extensively in vivo to a new challenge with the antigen in question. PMID- 8478623 TI - Synthesis of porphinatoirons having an alkyl amphiphilic chain and their O2 binding properties in lipid bilayers. AB - Synthesis and characterization of two amphiphilic tetraphenylporphinatoiron complexes having a glycerophosphocholine or an alkyl phosphoserine group are described. These porphinatoiron(II) complexes with 1-dodecyl-2-methyl-imidazole (L2MIm) were efficiently embedded in the bilayer of a phospholipid vesicle due to their high compatibility with lipids, similar to the heme substituted with four alkyl amphiphilic chains (lipid-heme). Oxygen transporting ability of the phospholipid vesicles embedded with hemes were similar to that of hemoglobin (Hb) in red blood cells. PMID- 8478624 TI - Temperature dependent coordination effects in base-off adenosyl and methylcobalamin by X-ray edge spectroscopy. AB - Examination of the role of base-off cobalamin species (where the 5,6 dimethylbenzimidazole ligand coordinated to cobalt is detached by protonation of the imidazole nitrogen) in differentiation between homolytic and heterolytic cobalt-carbon bond cleavage mechanisms is a primary step in better understanding B12-dependent enzyme catalysis. X-ray absorption edge spectroscopy provides the first direct structural evidence of five-coordination in base-off adenosyl- and base-off methylcobalamin complexes at room temperature. Integration of 1s-3d pre edge transitions of the base-off species reveals the dependence of coordination number on temperature. Gradual increases in 1s-3d transition intensities, as the temperature is increased from 180 K to 298 K, reflect a change in the coordination number from six (where a water molecule is presumed to occupy the coordination site vacated by the 5,6-dimethylbenzimidazole ligand) to primarily five-coordinate. Base-off configurations that strengthen the Co-C bond may be both decreasing the tendency for homolytic cleavage while increasing the tendency for hetrolytic Co(I) B12 formation. PMID- 8478625 TI - The binding of a complex cobalt ruthenium polyamine by deoxyribonucleic acid and a lipopolysaccharide: a model for a novel class of drugs. AB - In this paper we discuss the following: 1. Synthesis of [Co(H3CsarNHCH2pyRu(NH3)5)] (PF6)5, (CoRu). 2. Interaction of CoRu with calf thymus DNA and with lipopolysaccharide from Escherichia coli C (LPS) has been estimated using the absorption of the complex at 242 and 420 nm. 3. DNA and LPS increase the rate of fall of absorption at 420 nm due to autooxidation of the complex. 4. The fall in absorption of CoRu(II) at 420 nm can be used to give an approximate measure of binding to DNA and to LPS. 5. Both macromolecules are aggregated by CoRu at high concentrations and the cation and macromolecule complex can be removed by low speed centrifugation. 6. The DNA-CoRu complex can also be removed by high speed centrifugation when the cation concentration is too low to cause aggregation (20 microM CoRu/155 microM DNA-P). Absorption of redissolved complex at 420 nm is restored by reduction with ascorbic acid. 7. At saturation the ratio of mole CoRu bound/mole DNA-P is 0.16. PMID- 8478626 TI - Heterotopic ossification following primary total knee arthroplasty. AB - Heterotopic ossification is a rare complication following primary total knee arthroplasty and may be symptomatic if massive enough. The authors retrospectively reviewed 158 primary total knee arthroplasties from 1985 to 1989 and found 6 cases (3.8%) of heterotopic ossification. Patients were graded before and after surgery according to the Hospital for Special Surgery total knee arthroplasty score and their histories were reviewed for the presence of recognized risk factors for heterotopic ossification and whether a manipulation under anesthesia was performed. This report describes the incidence of, appearance of, and clinical risk factors for heterotopic ossification following primary total knee arthroplasty in this series. A radiographic grading system is proposed. PMID- 8478627 TI - A new radiographic method for detection of tibial component migration in total knee arthroplasty. AB - In a prospective study the accuracy of a new radiographic method, Matched Indicators for Radiographic Assessment (MIRA), used to assess tibial component migration in total knee arthroplasty was evaluated. Radiopaque markers were placed in the tibial component and the tibial metaphysis in a standardized way so that four vertical distances could be measured on standard radiographs. Subsidence during the first postoperative year was measured both with this new method and with roentgen stereophotogrammetric analysis in 27 Freeman-Samuelson total knee arthroplasties. The error of measurement of MIRA was determined using the known error of roentgen stereophotogrammetric analysis. The new method was found to be promising with an accuracy of 1 mm, and the correlation between MIRA and roentgen stereophotogrammetric analysis was high when subsidence exceeded this value. Therefore, subsidence of clinical importance should be detected with MIRA. The method is simple and well suited for routine follow-up examination of large patient materials. PMID- 8478628 TI - Reinfusion of whole blood after revision surgery for infected total hip and knee arthroplasties. AB - Because of its proven effectiveness in reducing the need for banked blood transfusions following total joint arthroplasty, the indications for postoperative blood retrieval were expanded to include seven cases of infected total knee or hip arthroplasties where a one-stage exchange procedure was performed. Each joint had been aspirated after surgery and had positive cultures but no gross pus at the time of revision surgery. Each of the operations included debridement with reimplantation of a cementless prosthesis under cover of intravenous antibiotics for 48 hours followed by oral treatment until discharge. Antibiotic-soaked morselized bone graft was used in all patients to restore deficient nonstructural bone. Wound drainage blood was retrieved and reinfused during the first 8 hours after surgery, averaging 958 cc. Banked blood usage averaged 2.4 U (88% homologous) with an average blood loss of 1,974 cc. One patient experienced shaking chills during a second reinfusion of 600 cc of blood without stoppage of the transfusion. Wound hematoma occurred in one patient but did not require surgical evacuation. No patient developed evidence of septicemia. PMID- 8478629 TI - Biomechanical analysis of a distally interlocked press-fit femoral total hip prosthesis. AB - This study was undertaken to compare the stability of a distally interlocked femoral prosthesis to a standard press-fit implant (Cementless Spotorno, Protek Co., Toronto, Canada). Five human femora were studied with each acting as its own control. All were tested in the locked mode followed by unlocked testing modes. The MTS 858 Biomaterials Testing System was used to test the implanted femoral stems under both pure torsional and pure axial loading. Distal interlocking increased the torsional stability by 320% (locked 4.05 Nm/degree; unlocked 1.25 Nm/degree) (P < .01) and the axial stability by 230% (locked 1,236.26 N/mm; unlocked 527.44 N/mm) (P < .01). the use of temporary distal interlock in cases where the initial stability of a press-fit implant is suboptimal should allow for improved biological fixation by minimizing micromotion at the stem-bone interface. PMID- 8478630 TI - Factors affecting deep vein thrombosis rate following total knee arthroplasty under epidural anesthesia. AB - A retrospective review was performed of 448 consecutive patients undergoing primary, unilateral, bicondylar, and cemented total knee arthroplasty under epidural anesthesia by three surgeons to determine factors contributing to deep vein thrombosis rate. All had venography on the fourth or fifth postoperative day and received aspirin and elastic stockings as their only thromboprophylaxis. The overall deep vein thrombosis rate was 41% (2% had proximal clots). The rate of deep vein thrombosis was not related to obesity, history of heart disease, hypertension, prior malignancy, smoking, diagnosis of osteoarthritis, duration of surgery, type of local anesthetic used, or the use of postoperative epidural analgesia. The rate of deep vein thrombosis varied significantly between surgeons: one surgeon had an overall deep vein thrombosis rate of 58% (proximal thrombi, 4%) whereas the other two surgeons had a deep vein thrombosis rate of 35% (proximal clot thrombi, 1%). A number of possible mechanisms to explain the variation in deep vein thrombosis rates between surgeons are provided. PMID- 8478631 TI - Femoral head autograft and contralateral total hip arthroplasty. AB - Femoral head autograft from a primary total hip arthroplasty side was used to supplement deficient bone stock on the contralateral revision side. Five patients (10 operations) were treated; all had excellent clinical results and full incorporation of the graft. The methods of treatment was found to be suitable in selected patients. PMID- 8478632 TI - Does the irrigation bag become infected in total hip arthroplasty? PMID- 8478633 TI - Mechanical evaluation of cadaver retrieval specimens of cementless bone-ingrown total hip arthroplasty femoral components. AB - Early retrieval prior to gross failure of implants can provide valuable information for critical issues in total joint arthroplasty. To evaluate fixation of the femoral component in total hip arthroplasty, two femoral specimens--one Mallory-Head (Biomet, Warsaw, IN) specimen and one AML (DePuy, Warsaw, IN) specimen--were retrieved after 2-8 years of successful use in active patients. Radiographs were made and evaluated for trabecular apposition to the porous coated areas of the stem, then torsional and axial load tests were performed for each specimen to determine micromotion and displacement at the bone-implant interface. Both implants had radiographic signs of bone ingrowth. No permanent rotational displacement was found in either specimen during torsional load testing, but rotational and axial micromotion were found in both. These findings indicate excellent fixation of implant to bone, and no slippage at the bone implant interface. The Mallory-Head implant had much greater elastic displacement than the AML, and histological examination showed cancellous bone ingrowth into the porous-coated portion of the Mallory-Head stem. The AML implant, which withstood much higher torsional loads, was found upon histological evaluation to have dense cortical-cancellous bone ingrowth. Strength of attachment of the metal implant to bone was good in both specimens, and neither had slippage at this interface. Differences in mechanical behavior can be attributed to the type of bone supporting the implant. The Mallory-Head implant had a severely worn titanium femoral head, so the joint was full of particulate metal debris.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478634 TI - Autopsy studies of the bone-cement interface in well-fixed cemented total hip arthroplasties. AB - Although knowledge of the clinical status of the implant is important, only instrumented mechanical testing of retrieved specimens provides quantitative assessment of implant fixation. This measurement allows placement of the implant along a continuum of loosening and is the foundation for the interpretation of subsequent findings. Analysis of implants that have been proven to be well fixed by instrumented testing reveals significant differences in the initial events in the loosening of femoral and acetabular components. Although radiolucencies were observed around all of these well-fixed femoral and acetabular components, the histology (and therefore the etiology) of the radiolucency is different and variable on the two sides of the articulation. The majority of femoral radiolucencies appear to be due to age and stress-related remodeling while particulate-induced bone resorption plays an important role in acetabular radiolucencies. A finding common to both sides of the articulation in these stable components, however, was intimate contact of bone with cement without any interposed soft tissue even after 17.5 years of service. Primary incompatibility and/or failure of the cement was not identified as a factor in initiating either femoral or acetabular component loosening. These studies document the long-term compatibility of bone with cement in bulk form. Improvements in cemented femoral component fixation should focus on stem design and cementing technique. Long-term acetabular component fixation can be improved by reduction or elimination of polyethylene wear and optimization of the bone-implant interface. PMID- 8478635 TI - Bone ingrowth into a porous-coated total shoulder component retrieved postmortem. AB - An uncemented porous-coated humeral component, which functioned in vivo for over 2 1/2 years, was retrieved postmortem and examined histologically. Radiographs of the specimen revealed close approximation to the endosteal cortex medially and laterally. Apposition was limited or absent anteriorly and posteriorly. The overall extent of bone ingrowth was approximately 11% of the available pore volume with over 95% of ingrowth occurring in the medial and lateral quadrants. Bone ingrowth was limited anteriorly and posteriorly to regions in which spot welds were identified radiographically. There were no loose beads or coating failure observed. PMID- 8478636 TI - A quantitative study of bone and soft tissues in cementless porous-coated acetabular components retrieved at autopsy. AB - The authors examined 11 cementless acetabular components of one design retrieved at autopsy and made observations concerning tissue ingrowth and local tissue reaction, radiographic-histologic correlation, and the distribution of particulate wear debris. The cups were hemispherical in design with a commercially pure titanium fiber-metal porous coating. All of the prostheses were implanted with screws. The implants were in place for an average of 41 months (range, 5 weeks to 75 months). Ten of the cups had bone ingrowth, with the average volume fraction being 12.1 +/- 8.2%. There were no differences in the amount of bone ingrowth when the component was partitioned into nine anatomic regions. However, there was more bone adjacent to screw holes through which screws were inserted compared with empty screw holes. As the number of radiolucent zones increased on the clinical radiographs less bone ingrowth was observed histologically. The amount of metal debris in holes with screws and holes without screws was similar. In the longest term cases, polyethylene debris was noted within empty screw holes, but no granulomatous reactions or osteolytic processes were observed. PMID- 8478637 TI - Choline acetyltransferase and calcitonin gene-related peptide immunoreactivity in motoneurons after different types of nerve injury. AB - This study examined changes in choline acetyltransferase and calcitonin gene related peptide immunoreactivity in hypoglossal motoneurons of rats at 1, 3, 7, 20 and 50 days after three types of nerve injury: crush, transection and resection. Peripheral reinnervation was assayed by retrograde labelling of the motoneurons after injections of the exogenous protein, horseradish peroxidase, into the tongue. Maximal reduction in choline acetyltransferase immunostaining occurred at seven days after nerve damage and the amount of the decrease was related to the nature of the injury. The recovery of choline acetyltransferase to normal levels was related to the timing of reinnervation after nerve crush, but not after transection or resection injuries. In contrast to these findings, a rapid increase in calcitonin gene-related peptide immunoreactivity preceded the decrease in choline acetyltransferase levels. A striking increase in calcitonin gene-related peptide immunoreactivity was observed at one day postoperative and was maximal at three days postoperatively for all injuries. Later changes in calcitonin gene-related peptide levels were dependent on the type injury. Increased calcitonin gene-related peptide staining persisted to 20 days after nerve crush. After nerve transection or resection, calcitonin gene-related peptide immunoreactivity decreased to basal levels at seven days postoperatively. This declination was followed by a second rise in calcitonin gene-related peptide immunolabeling at 20 days for nerve transection or 50 days after resection. Nearly complete reinnervation was established by 20 days after nerve crush. At 50 days after transection, less than half the number of normally-labelled neurons contained horseradish peroxidase. At this time only 1% of those whose axons had been resected were labelled. These observations suggest that different mechanisms regulate the responses of choline acetyltransferase and calcitonin gene-related peptide to nerve injury. The present results indicate that choline acetyltransferase levels in motoneurons can not be used to predict either the likelihood of or the timing of reinnervation after nerve transection or resection. However, our results strengthen the premise that an increased of calcitonin gene-related peptide immunoreactivity serves as a reliable index for predicting nerve regeneration/reinnervation after cranial nerve injury. PMID- 8478638 TI - Co-localization of the beta-subtype of protein kinase C and phosphorylation dependent immunoreactivity of neurofilaments in intact, decentralized and axotomized rat peripheral neurons. AB - The localizations of protein kinase C-beta-immunoreactivity and phosphorylation dependent immunoreactivity of neurofilaments were compared in rat dorsal root, hypogastric, and superior cervical ganglia. In all the ganglia studied, protein kinase C-beta and phosphorylation-dependent immunoreactivity of neurofilaments were co-localized in nerve fibres, and no fibres with only protein kinase C-beta immunoreactivity or phosphorylation-dependent immunoreactivity of neurofilaments were observed. Most intense perikaryal protein kinase c-beta and phosphorylation dependent neurofilament-staining were seen in large dorsal root ganglion neurons, whereas in the superior cervical ganglion only very faint protein-kinase C-beta and no phosphorylation-dependent staining was seen in the neuronal cell bodies. Both decentralization and axotomy of the superior cervical ganglion induced an accumulation of protein-kinase C-beta-immunoreactivity and phosphorylation dependent immunoreactivity of neurofilaments in the majority of neuronal perikarya. The accumulation was first observed at 1-2 days postoperation and it persisted up to 6-10 days postoperation. In strongly labelled decentralized neuronal perikarya, precipitation of immunoreactivity was seen near the cell and nuclear membranes, whereas in axotomized neurons, immunoreactivity was often concentrated as a unipolar clump in the cytoplasm. The results show that protein kinase C-beta-immunoreactivity and phosphorylation-dependent immunoreactivity of neurofilaments are colocalized in intact rat peripheral ganglia and that both accumulate transiently in cell bodies of the superior cervical ganglion after decentralization and axotomy. PMID- 8478639 TI - The influence of fibronectin and laminin during Schwann cell migration and peripheral nerve regeneration through silicon chambers. AB - The ability of extracellular proteins to influence the regenerative process was examined in Sprague-Dawley rats. Silicon chambers, filled with sterile saline solutions of cytochrome-c, fibronectin, laminin, a combination of fibronectin and laminin, or nerve growth factor were surgically implanted between the severed ends of sciatic nerves to form gaps of 18 mm. Four months later, the various groups were examined to determine the success of regeneration. The incidence of cable formation that bridged the gap was similar in all groups. The group of animals that had implants containing the combination of fibronectin/laminin had increased numbers of myelinated axons in the regenerated segment within the chamber and in the distal sciatic tributary nerves. Horseradish peroxidase labelling demonstrated that increased numbers of sensory and motor neurons in the fibronectin/laminin group had regenerated axons across the gap into the distal tributaries of the sciatic nerve. The effect of the various agents on non neuronal cells was measured by immunohistochemical staining with S-100 antibodies to determine the effects on Schwann cell migration. Silicon chambers, filled with sterile saline solutions of fibronectin, laminin, fibronectin/laminin, nerve growth factor, or cytochrome-c, were surgically implanted to form 5 mm gaps between severed sciatic nerve ends. Ten days later, Schwann cell migration into the bridging cables was examined in each group. Analysis revealed a greater influx of Schwann cells migrating into the regenerating segments in the fibronectin, the laminin, and the combination fibronectin/laminin groups compared to the control group (cytochrome-c). PMID- 8478640 TI - He-Ne laser irradiation affects proliferation of cultured rat Schwann cells in a dose-dependent manner. AB - Schwann cell proliferation is considered an essential part of Wallerian degeneration after nerve damage. Laminin, an important component of the extracellular matrix and produced by Schwann cells, provides a preferred substrate for outgrowing axons. To study whether low energy (He-Ne) laser irradiation may exert a positive effect on nerve regeneration through an effect on Schwann cells, its effect was evaluated in vivo. Schwann cells were isolated from sciatic nerves of 4-5-day-old Wistar rates and cultured on 96-multiwell plates. The cells were irradiated by a He-Ne laser beam (632.8 nm, 5.98 mW) that was optically expanded to a beam width of 4 mm. During irradiation the plate was kept in an air-tight box equilibrated with humidified air containing 5% CO2 and kept at 37 degrees C. At three consecutive days, starting either at day 5 or day 8, cells were irradiated each day for 0.5, 1, 2, 5 or 10 min. Both cell number and laminin production were determined for each irradiation condition (n = 5) within one experiment. Schwann cells that were irradiated from day 8 on were hardly affected by laser irradiation. However, the proliferation of cells that were irradiated starting on day 5 was significantly increased after 1, 2, and 5 min of daily irradiation, compared to non-irradiated control cultures. The laminin production per cell of these Schwann cells was not significantly altered. From these results we conclude that He-Ne laser irradiation can modulate proliferation of rat Schwann cells in vitro in a dose-dependent manner. PMID- 8478641 TI - Periterminal synaptic organization of primary afferents in laminae I and IIo of the rat spinal cord, as shown after anterograde HRP labelling. AB - The fine structure and periterminal synaptology of the primary afferent terminations in laminae I and IIo are examined in the rat, following anterograde labelling with horseradish peroxidase applied to the right C5-dorsal root. Labelled varicosities observed along the terminal arbors in parasagittal thick sections were relocated in ultrathin sections by electron microscopy. The labelled terminal profiles generated by the three primary afferent plexuses which can be identified by light microscopy in laminae I-IIo had similar fine structural features, except that axo-axonal contacts, although rare, were more frequent in the medial network plexus. Primary boutons were packed with agranular spherical vesicles and some large granular vesicles, and were mostly presynaptic to profiles of dendritic trunks of marginal cells. Unlabelled axonal profiles, either light with some flattened vesicles, or dense with round vesicles, were also presynaptic at symmetrical or asymmetrical contacts, respectively, to those dendritic profiles. It is suggested that such knobs of intrinsic origin are responsible for postsynaptic modulation of the primary noxious input. Although the 20 microns wide lamina IIo belongs cytoarchitectonically to lamina II and can be distinguished from lamina I by a decreased amount of myelinated fibres and large dendritic profiles, the periterminal synaptology was here found to be the same as in lamina I. PMID- 8478642 TI - Spinule formulation in the fish retina: is there an involvement of actin and tubulin? An electronmicroscopic immunogold study. AB - During light-adaptation dendrites of teleost horizontal cells form finger-like processes, called 'spinules', which are characterized by synaptic membrane densities. To investigate the involvement of cytoskeletal elements in the formation and retraction of spinules, effects of the microtubule and actin inhibitors colchicine and cytochalasin D were examined by injection into the vitreous. Both substances inhibited the light-induced spinule formation. The ultrastructural immunolocalization of tubulin revealed labelling of dendrites only in their proximal parts. The distal parts of dendrites which invaginate into cone pedicles were free of label. Treatment with anti-actin revealed immunoreactivity along the entire length of dendrites up to the dendritic terminals. The spinules, however, showed no labelling. This finding does not support the hypothesis that spinules are protruded by actin polymerization. After cytochalasin D treatment the density of label in the dendritic terminals was enhanced by a factor of three, which suggests an accumulation of actin. Thus, spinule inhibition by cytochalasin D is probably caused by distortion of a functional actin network in the dendritic terminals. PMID- 8478643 TI - Basement membranes during development of human nerve: Schwann cells and perineurial cells display marked changes in their expression profiles for laminin subunits and beta 1 and beta 4 integrins. AB - The formation of the connective tissue compartments of human sciatic and tibial nerves was studied with special reference to the maturation of the basement membranes during foetal development (11-35 weeks of gestation). All Schwann cells were surrounded by continuous basement membranes as early as at week 11, while the perineurial cells became covered by basement membranes gradually between weeks 17 and 35, as estimated by electron microscopy. The first laminin subunits detectable within the nerve were the B1, B2 and M chains. These laminin subunits were present in Schwann cell basement membrane zone at week 11, and in the perineurium at week 17 and later. Laminin A and S chains were first detected at 26 weeks in the perineurium, and at a later stage (35 weeks) on Schwann cells. In mature nerves, all these five laminin chains could be demonstrated in both Schwann cell and perineurial cell basement membrane zones, although A, S and B2 chains predominated in the perineurium, and M, B1 and B2 were the predominant chains in Schwann cell basement membranes. Beta 1 and beta 4 integrins were expressed by all Schwann cells in samples from the youngest foetuses (11-17 weeks). At 22-35 weeks, however, only a subpopulation of Schwann cells stained positively for beta 1 and beta 4 integrins. Perineurial cells expressed beta 1 integrins at all ages studied. Staining for beta 4 integrin in perineurium became detectable and intensified concomitant with the formation of structural basement membranes. The results demonstrate that Schwann cells and perineurial cells change their laminin and integrin expression profiles during the maturation of peripheral nerve. PMID- 8478644 TI - Cycloheximide mimics effects of oestradiol that are linked to synaptic plasticity of hypothalamic neurons. AB - The synaptic connectivity of the rat arcuate nucleus, a hypothalamic area rich in oestradiol receptors, is rapidly affected by physiological modifications of hormonal levels. A rise of oestradiol in plasma elicits a coordinated neuronal glial response that begins with a rapid fall in the number of small (< 10 nm) intramembrane particles and a rapid increase in the number of large (> 10 nm) intramembrane particles in neuronal membranes, followed by a modification in the branching of astrocytic processes and finally results in decreased number of axo somatic synapses and increased glial wrapping of the neuronal somas. In the course of a series of studies aimed to test possible non-genomic effects of oestradiol on neuronal membranes we analyzed the effect of the systemic administration of the protein synthesis inhibitor cycloheximide on the ultrastructure of arcuate neurons and granule cells of the cerebellar cortex, an area of the brain with low levels of estrogen receptors. Cycloheximide resulted in a significant inhibition of protein synthesis in hypothalmus and cerebellum of ovariectomized rats. Under these circumstances, the number of small intramembrane particles was reduced in hypothalamic and cerebellar neuronal membranes while the number of large intramembrane particles showed a decrease in cerebellar membranes and a transient increase in arcuate neuronal somas. Furthermore, cycloheximide resulted in an increased glial wrapping of arcuate neuronal somas but not of cerebellar granule cells. The ensheathing of arcuate neurons by glial was associated with a 41% decrease in the number of axo-somatic synapses. These results indicate that the protein synthesis inhibitor cycloheximide may elicit the integrated neuronal-glial response that is associated with the hormonally induced remodelling of synaptic contacts on arcuate neurons. PMID- 8478645 TI - Reciprocal axo-axonal synapses between the common inhibitor and excitor motoneurons in crustacean limb muscles. AB - Nerve terminals of the common inhibitor motoneuron in a crab (Eriphia spiniforns) limb closer muscle and in a crayfish (Procambarus clarkii) limb accessory flexor muscle make neuromuscular synapses with the muscle membrane (postsynaptic inhibition) as well as axo-axonal synapses with the terminals of the excitatory axon (presynaptic inhibition). That transmission is from the inhibitor to the excitor terminals at these axo-axonal synapses is indicated by the occurrence on the inhibitor membrane of presynaptic dense bars denoting sites of transmitter release. Axo-axonal synapses with the opposite polarity, in which transmission is from an excitatory onto an inhibitory terminal, were occasionally seen either adjacent to or separate from the inhibitory axo-axonal synapse. Nerve terminals of the specific inhibitor in the crayfish opener muscle were seen to make numerous axo-axonal output synapses upon excitatory nerve terminals but excitor nerve terminals were not seen to make output synapses onto inhibitor terminals. Thus reciprocal axo-axonal synapses appear to be a feature of the common inhibitor but not of the specific inhibitor. The excitor-to-inhibitor component of these reciprocal synapses may serve to limit transmitter output in the common inhibitor axon by activating glutamateB receptors which facilitate efflux of K+ and hyperpolarization of the membrane. PMID- 8478646 TI - Ultrastructure and permeability of the Schwann cell layer surrounding the giant axon of the squid. AB - The ultrastructure of the Schwann cell layer surrounding the giant axon of the squid Alloteuthis subulata is described, and the permeability of extracellular compartments assessed by exposure to electron-dense tracers. Morphometric analysis is used to deduce the number, size and shape of the Schwann cells, and the routes for ion flux across the Schwann cell layer. Axons (mean diameter 233 microns) were surrounded by a 1-2 microns thick layer of Schwann cells which were approximately 1 micron thick, approximately 70 microns long and approximately 23 microns wide. There were around 62,000 Schwann cells per cm2 axon surface. The outer (abaxonal) surface of the Schwann cells was invaginated, with evidence for a covering of fine Schwann cells processes; the inner (adaxonal) surface of the Schwann cells was less folded. The percentage area occupied by mesaxonal cleft openings to the axon and to the basal lamina was 0.02% and 1.09% respectively. A system of tubules, the glial tubular system, occupied 3.9% of the Schwann cell volume, and opened to both axonal and basal lamina surfaces, with more elaborate lattice-like clusters towards the basal side of the cell. Tubule openings accounted for 0.26% of the surface area facing the axon and 0.37% of the area facing the basal lamina (where there was greater clustering of openings). The electron dense tracers horseradish peroxidase, ionic lanthanum and tannic acid filled mesaxon clefts, glial tubular system and periaxonal space. If ion flux occurred via the mesaxonal clefts, a theoretical series resistance (Rsth) of > 20 omega cm2, would be predicted, whereas if it occurred via the tubular system, the figure would be < 2 omega cm2, closer to physiological estimates. The results presented show that the glial tubular system is likely to be the major route for ion flux into and across the Schwann cell layer, and for clearance of K+ from the periaxonal space during periods of axonal stimulation. The implications for K+ homeostasis in the axonal microenvironment are discussed. PMID- 8478647 TI - Reactive astrocytes in the kainic acid-damage hippocampus have the phenotypic features of type-2 astrocytes. AB - Kainic acid treatment, a model of temporal lobe epilepsy, induces Ammon's horn sclerosis characterized by degeneration of CA3 pyramidal neurons and reactive gliosis. We now report that in kainic acid treated rats, reactive astrocytes in the hippocampus are A2B5 immunopositive and express GAP-43 immunoreactivity. A2B5 is a cell surface ganglioside selectively expressed in the glial O-2A lineage (oligodendrocytes and type-2 astrocytes in vitro). Since A2B5-positive cells were also GFAP immunoreactive, our observation suggest that hippocampal-reactive astrocytes in the epileptic process are type-2 astrocytes. GAP-43 is a membrane associated phosphoprotein involved in neurite outgrowth. In vitro analysis showed that the glial O-2A lineage may express this phosphoprotein. In this study, we found that GAP-43 was coexpressed in astrocytes with A2B5 suggesting that in vivo as in vitro type-2 astrocytes express GAP-43. PMID- 8478648 TI - The usefulness of the preoperative electrocardiogram. PMID- 8478649 TI - Anesthesia systems. Part II: Operating principles of fundamental components. AB - This second article in a 2-part series on the operation of principal components within Narkomed anesthesia systems describes the function and compensation mechanisms of the Drager 19.n vaporizer, the operating principles of the anesthesia ventilator-electronic, the structure and mechanics of the pressure limit control, and the 3 basic monitoring systems built into the anesthesia system. Part II of this series builds on the data published in part I (J Clin Monit 1992;8:295-307). PMID- 8478650 TI - Artifact detection and removal during auditory evoked potential monitoring. AB - Various artifacts can distort or obscure evoked potential waveforms. The algorithms presented in this paper scan the output electroencephalographic signal for artifacts during evoked potential recordings. If possible, the artifact is removed; if not possible, that sweep is excluded from the averaging process required to raise the evoked response above the background electroencephalographic activity. An artifact is detected if 1 or more amplitude or frequency parameters exceed a threshold. These thresholds have been determined after constructing histograms of the parameters concerned using a number of control evoked potential recordings containing no visually recognizable artifacts. The distributions of the parameters shown by these histograms give information about their normal range. The method improves the quality of the waveform in many cases, but its effectiveness strongly depends on the characteristics of the artifacts concerned. PMID- 8478651 TI - The esophageal temperature gradient in anesthetized children. AB - OBJECTIVE: Our objective was to study the effect of the temperature of the anesthetic gas mixture (AGM) on esophageal temperature measurements made in children whose tracheas had been intubated for anesthesia. We also sought to establish the optimal site for the temperature sensor in the esophagus and to find a way to accurately place the sensor. METHODS: Special esophageal temperature probes with thermistors located at 1-cm intervals were used for data collection on a multiplex system. Esophageal temperature measurements were made every 15 minutes for a period of 120 minutes in anesthetized children receiving heated (n = 30) and unheated (n = 30) anesthetic gases. RESULTS: The temperature of the AGM (p < 0.001), the site of measurement (p < 0.001), and the interaction between AGM temperature and site of measurement (p < 0.007) all had a significant effect on esophageal temperature measurements. This effect was greatest at a point 3 cm distal to the level of the tip of the endotracheal tube when AGMs were not heated. CONCLUSION: We conclude that best results are obtained when care is taken to place the thermistor in the lower quarter of the esophagus. (We provide a simple formula for calculating this placement in pediatric patients of varying ages.) Placing the probe by acoustic criteria cannot consistently be relied on to provide good thermometry. PMID- 8478652 TI - Absence of a capnogram after positive end-expiratory pressure. AB - OBJECTIVE: The objective of this study was to evaluate the effect of positive end expiratory pressure (PEEP) on capnography. DESIGN: The study design was experimental and open, and it was performed in the Anesthesiology Experimental Research Laboratory. METHODS: Six dogs (9.8 +/- 0.8 kg) were anesthetized and intubated. The animals' lungs were ventilated with a tidal volume of 137 +/- 34 ml and a respiratory frequency of 34 +/- 10 breaths/min to produce a PaCO2 of 35 to 45 mm Hg. Application of 20 cm H2O of PEEP was initiated for 1 minute, then repeated twice after 10-minute stabilization periods. Arterial pH and gas tensions were measured, and capnogram, airway gas flow, and airway pressure were recorded continuously. Airway gas flow was electronically integrated to calculate tidal volume. RESULTS: Mean values before application of PEEP were as follows: pHa, 7.37 +/- 0.04 mm Hg; PaCO2, 37.1 +/- 3.2 mm Hg; PaO2, 93.4 +/- 1.6 mm Hg; and PETCO2, 32.0 +/- 3.5 mm Hg. Compliance of the ventilator circuit was 3.3 ml/cm H2O. Mean deflation lung-thorax compliance was 41.5 +/- 10.3 ml/cm H2O. After application of PEEP, no capnogram was reported for 1 to 6 breaths, an average of 2.7 +/- 1.8 breaths. CONCLUSION: These results demonstrated that absence of gas flow immediately after the application of PEEP may transiently abolish a capnogram when the lung volume increases. PMID- 8478653 TI - The effect of dyshemoglobins on pulse oximetry: Part I, Theoretical approach and Part II, Experimental results using an in vitro test system. AB - Pulse oximeters are known to be inaccurate in the presence of elevated concentrations of carboxyhemoglobin and methemoglobin. This paper attempts to alleviate some of the confusion that exists between fractional and functional saturation, and to clarify the comparison of each with SpO2. A series of theoretical relationships between pulse oximeter reading (SpO2) and actual oxygen saturation (both fractional and functional) is derived using simple absorption theory. The theoretical relationships are checked using an experimental in vitro test system. This consists of a blood circuit containing a model finger, capable of simulating the pulsatile transmission signals through a real finger. Theoretical predictions and experimental results are compared and are found to agree well in the presence of carboxyhemoglobin, but less well with methemoglobin. Possible reasons are discussed. PMID- 8478654 TI - Urinary bladder temperature monitoring in extensively burned patients. PMID- 8478655 TI - Curable neoplasms and the ethics of clinical trials. PMID- 8478656 TI - Prognostic factors in medulloblastoma, including DNA ploidy. AB - PURPOSE: DNA ploidy status, completeness of surgical resection, use of chemotherapy, adequacy of radiation therapy, metastatic stage, sex, and age at diagnosis were evaluated as predictors of relapse in 58 patients with cerebellar medulloblastoma. METHODS: Flow cytometry (FCM) and/or image analysis (IA) were used to characterize tumor DNA ploidy. Twelve tumors (21%) were found to be aneuploid, 11 (19%) tetraploid, and 35 (60%) diploid. RESULTS: The most significant predictors of relapse in univariate analyses were the adequacy of radiation (> or = 50 Gy) (P = .02), metastatic staging (P = .05), completeness of resection (P = .085), and DNA ploidy status (diploid/tetraploid v aneuploid; P = .11). When the 52 patients who received > or = 50 Gy were included in a multivariate Cox model analysis, those with diploid/tetraploid tumors had fewer recurrences than those with aneuploid tumors (relative risk, 0.33; 95% confidence interval, 0.12 to 0.89; P = .03). Patients with complete resections (P = .07), or with stage M0 disease (P = .06) had fewer recurrences than other patients, but these factors were not independent predictors of outcome. DNA ploidy status was correlated with age; 10 of the 12 aneuploid tumors were found in children ages 3 to 10 years. Age, sex, and the use of chemotherapy were not prognostically significant in these analyses. CONCLUSION: The adequacy of radiation dose and DNA ploidy were the most important prognostic factors in this series. Contrary to previous reports, when corrected for adequacy of treatment, DNA aneuploidy was associated with a poor outcome. By multivariate analyses, DNA ploidy was an independent variable, even when controlling for extent of surgical resection and metastatic stage. PMID- 8478657 TI - Escalating dose of continuous infusion combination chemotherapy for refractory neuroblastoma. AB - PURPOSE: This trial was undertaken to determine if a continuous infusion format with increased dose-intensity had antitumor activity with tolerable toxicity in patients with advanced neuroblastoma. PATIENTS AND METHODS: Forty heavily pretreated patients with refractory or progressive neuroblastoma received continuous infusion doxorubicin, cisplatin, and etoposide along with bolus ifosfamide in a dose-escalation format. A total of 79 courses of chemotherapy were administered at five different dose levels. RESULTS: Fifteen of 35 assessable patients (43%) achieved either a partial response (PR) or complete response (CR), including five patients with a CR, three with a very good PR (VGPR), and seven with a PR. Hematologic toxicity was severe, but reversible, and other toxicities, although significant, were tolerable and much less than that accepted in a bone marrow transplantation (BMT) setting. CONCLUSION: This investigation illustrates that response is possible even in an extremely poor prognosis group of patients, and it suggests that such a regimen may be effective if given before disease progression occurs. PMID- 8478658 TI - Combined continuous infusion etoposide with high-dose cyclophosphamide for refractory neuroblastoma: a phase II study from the Societe Francaise d'Oncologie Pediatrique. AB - PURPOSE: Patients older than 1 year with stage IV neuroblastoma who fail to achieve complete remission (CRem) have a particularly poor long-term prognosis. In an attempt to improve the outcome of these refractory patients, we tested a new drug combination. PATIENTS AND METHODS: Twenty-nine children with advanced neuroblastoma (27 stage IV and two stage III) were entered onto this phase II study. All were refractory to conventional chemotherapy and had measurable disease at the time of the trial. The regimen was a combination of high-dose cyclophosphamide (2 g/m2/d) on days 2, 3, and 4, and etoposide (VP16; 50 mg/m2/d) by continuous intravenous (IV) infusion on days 1 to 5. A pharmacokinetic study of VP16 was conducted in eight patients to determine whether the goal of persistent plasma levels between 1 and 5 micrograms/mL was achieved. RESULTS: Patients received a median of two courses, for a total of 58 courses. The median interval between each course was 32 days. In the 28 assessable patients, the overall response rate was 43%, with one CRem and 11 partial remissions (PRems). No life-threatening complication was observed in these heavily pretreated patients. The median duration of neutropenia (< 5 x 10(9)/L) was 14 days, and that of thrombocytopenia (< 50 x 10(9)/L) was 11 days. The overall incidence of sepsis was 27%. Gastrointestinal toxicity was frequent, but mild. Electrolyte disturbance with antidiuretic hormone (ADH)-like syndrome occurred in eight courses, but resolved rapidly. Grade > or = 2 hemorrhagic cystitis was observed in three courses. No cardiac toxicity was observed. There were no treatment related deaths. Pharmacokinetic analysis showed that mean steady-state plasma levels (Css) of VP16 were greater than 1 microgram/mL during all the courses. CONCLUSION: This new drug combination appears to be effective in advanced neuroblastoma. Its toxicity remains manageable, with no life-threatening complications. Further evaluation in patients with less-advanced disease is warranted. PMID- 8478659 TI - Role of computed tomography in the staging of primary melanoma. AB - PURPOSE: To evaluate the role of body computed tomography (CT) for the staging of patients with early melanoma. PATIENTS AND METHODS: A total of 151 new patients with American Joint Committee (AJC) clinical stage I, II, and III melanoma who received a CT scan of at least the chest and abdomen are the subject of this study. CT scans considered suspicious for metastases were reviewed again by one of the investigators (A.McB.C.). RESULTS: Of 151 patients, 63 had AJC clinical stage I, 61 stage II, and 23 stage III disease. In addition, one patient each had primary melanoma of the anal canal, esophagus, or vulva. Twenty-nine (19%) of 151 patients had a CT scan that was considered suspicious for metastases. The most common radiologic findings were single hepatic, and single or multiple pulmonary nodules. Of these 29 patients with suspicious scans, 24 subsequently proved to have benign processes by biopsy or follow-up studies, three had second primary tumors (well-differentiated lymphocytic lymphoma, Hodgkin's disease, and renal cell carcinoma), and only two were found to have metastatic melanoma. Of these two patients, one had regional nodal disease (unsuspected on physical examination) and one had distant nodal metastases. CONCLUSION: Body CT is not a useful imaging study in the detection of occult metastases in patients with primary melanoma. Although body CT commonly shows suspicious radiologic abnormalities in patients with early melanoma, these abnormalities most likely represent benign processes or a second primary tumor, rather than metastatic melanoma. The value of body CT in patients who present with nodal metastases needs further study. PMID- 8478660 TI - Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy. AB - PURPOSE: We reviewed survival data of patients with low-grade lymphoma entered on Southwest Oncology Group (SWOG) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) in such patients. PATIENTS AND METHODS: We identified all patients with low-grade lymphoma, no prior therapy, and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204, 7426, or 7713. Survival data for this group of patients were correlated with pretreatment prognostic factors, including histology, patient age, sex, symptom status, performance status, bone marrow or extranodal involvement, and the number of disease sites. The effect of maintenance treatment was also assessed. RESULTS: Four hundred fifteen patients met criteria for inclusion in the study group. With median follow-up periods of 12.8 years (maximum, 19.8 years), the median survival duration was 6.9 years. Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology, age greater than 40 years, male sex, B-symptom status, and SWOG performance status greater than 1. Multivariate regression analysis showed histology, age, and sex to be independent predictors of survival. There was no definite survival plateau of cured patients in any subgroup, although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25%. Maintenance therapy did not prolong survival. CONCLUSION: Doxorubicin-containing treatment did not prolong the overall median survival of low-grade lymphoma patients compared with results with less-aggressive programs. PMID- 8478661 TI - Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. AB - PURPOSE: To determine better the activity of high-dose interleukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. PATIENTS AND METHODS: Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emeryville, CA) 1.33 mg/m2 (approximately 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 x 10(6) U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71) were assigned to receive IL-2 alone. RESULTS: Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11%) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17%) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90% reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12+ to 26+ months in duration. CONCLUSION: We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma. PMID- 8478662 TI - Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia. AB - PURPOSE: Since the only three cases of granulocytic sarcoma among patients with acute myeloid leukemia (AML) seen at our institution during the last 12 years were each associated with the 8;21 translocation [t(8;21)], we sought to determine if this association is specific and more frequent than previously recognized. PATIENTS AND METHODS: We report three patients with AML and t(8;21) who developed granulocytic sarcomas, and review the world literature. RESULTS: Between 1980 and 1992, 53 cases of AML French-American-British (FAB) M2 were identified at our institution. Eight (15%) patients had t(8;21). Three of these eight patients (38%) developed granulocytic sarcoma. All three of our patients received conventional intensive antileukemic chemotherapy yet had short relapse free survival durations. Several series of patients with t(8;21) report that granulocytic sarcomas occur in approximately 18% of this population, which is four times the expected incidence in AML. Thirty-seven cases have been previously reported. Although karyotype analyses were not reported in many cases of granulocytic sarcoma in the literature, the vast majority of abnormal karyotypes in patients with AML involved t(8;21). Recent work with a cell line derived from a patient with t(8;21) indicates that such cells are unusually adherent to culture bottles and are aggregable CONCLUSION: Our data suggest that this association is more common than generally recognized and may be specific. Patients with t(8;21) should be observed closely for signs and symptoms of granulocytic sarcoma. These patients may have a less favorable prognosis than other patients with t(8;21). Cooperative oncology groups should retrospectively identify patients with AML and t(8;21) who had a poor outcome to determine if they had a disproportionate incidence of granulocytic sarcoma. If so, aggressive therapy such as bone marrow transplantation may be warranted early in the therapeutic strategy. PMID- 8478663 TI - Yttrium 90-labeled antiferritin followed by high-dose chemotherapy and autologous bone marrow transplantation for poor-prognosis Hodgkin's disease. AB - PURPOSE: This study was undertaken to examine the feasibility of combining radiolabeled antibody therapy with high-dose chemotherapy followed by autologous bone marrow transplantation in patients with poor-prognosis Hodgkin's disease. PATIENTS AND METHODS: Patients were entered onto this protocol if they had chemotherapy-resistant disease, bulky disease, or extensive prior therapy. Patients received yttrium-labeled antiferritin on day -13, -12, or -11, followed by high-dose cyclophosphamide, carmustine, and etoposide (CBV) on days -6 to -3, and then bone marrow infusion on day 0. RESULTS: Twelve patients received both radiolabeled antibody and high-dose chemotherapy followed by autologous transplantation. Two additional patients started the study, but were unable to complete all therapy. Four of 12 patients experienced early transplant-related mortality. Four patients are alive more than 2 years following transplantation and three are free from disease progression at 24+, 25+, and 28+ months following transplantation. The progression-free survival rate at 1 year is estimated to be 21%. Considering the poor prognostic characteristics of these patients, toxicity on this protocol was not necessarily greater than that observed with high-dose chemotherapy alone. CONCLUSION: This report demonstrates the feasibility of combining radiolabeled antibody therapy with high-dose chemotherapy and autologous bone marrow transplantation. PMID- 8478664 TI - High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant. AB - PURPOSE: To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS: Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm). RESULTS: Response to high dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor. CONCLUSION: Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS. PMID- 8478665 TI - Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. AB - PURPOSE: A single-center, prospective, nonrandomized trial was conducted to evaluate therapeutic results of a short-term program of chemotherapy followed by locoregional radiotherapy in stage I or II intermediate/aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1985 to 1990, 183 consecutive patients with a diagnosis of NHL (Working Formulation [WF] E through J excluding Burkitt's type), Ann Arbor stage I or II, and no more than three sites of disease involvement were treated with four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (six cycles in partial responders). Radiation therapy to initial sites of disease involvement (40 to 44 Gy) and to proximal uninvolved nodal region (36 Gy) was delivered shortly after completion of the chemotherapy program. RESULTS: The complete remission (CR) rate was 98% at the end of combined therapy. Diagnostic excision of all measurable disease was performed in 33% of patients. In the remaining patients, 87% achieved CR with chemotherapy and 11% with radiation therapy, while three patients failed to achieve CR. After a median follow-up of 51 months, 26 patients have relapsed and 25 have died. The 5-year relapse-free and total survival rates were 83%. Aside from age older than 60 years, no other factor such as histology, stage, extranodal disease, bulky lymphoma, or abnormal lactic dehydrogenase (LDH) could predict for treatment outcome. There was a trend toward higher relapse rate for patients achieving CR at the time of radiation therapy (31%) as opposed to patients achieving CR with chemotherapy (15%) or with initial surgery (10%). Treatment was well tolerated and no deaths due to acute toxicity were observed. CONCLUSION: For patients who present with limited-stage, aggressive NHL, a short course of CHOP chemotherapy followed by locoregional irradiation is safe, highly effective, and curative for most. Therefore, at the present time this approach can be regarded as standard therapy for these patients. PMID- 8478666 TI - Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. AB - PURPOSE: To define the imaging and biodistribution characteristics of iodine 131 labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell surface antigen expressed by human renal cell carcinoma (RCC). PATIENTS AND METHODS: G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level. RESULTS: Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250 negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250 positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%. CONCLUSION: 131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential. PMID- 8478667 TI - Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer. AB - PURPOSE: Enhanced fluorouracil (FUra) cytotoxicity caused by recombinant interferon alfa-2b (rIFN-a) has been reported, but the mechanism, optimal dose, and schedule remain unknown. Therefore, a phase I and pharmacokinetic study of FUra with escalating doses of rIFN-a was initiated. PATIENTS AND METHODS: FUra (750 mg/m2/d) was given by continuous intravenous (IV) infusion for 5 days. rIFN a (0.1 to 15 x 10(6) U/m2/d) was given subcutaneously (SC) daily for 5 days concurrent with FUra. Courses were repeated every 14 to 21 days. Forty-four patients were enrolled; 39 received at least two courses. During the first course of therapy, FUra levels before and after administration of rIFN-a were quantitated in 26 patients by high-pressure liquid chromatography. RESULTS: The maximum-tolerated dose of rIFN-a was 10 x 10(6) U/m2/d. Stomatitis was dose limiting. Three partial and five minor responses occurred. Interpatient pharmacokinetics showed that rIFN-a did not alter steady-state plasma concentration (Css; range, 0.77 +/- 0.35 mumol/L to 1.85 +/- 0.48 mumol/L), elimination half-life (t1/2; mean, 9.7 +/- 4.3 minutes), area under the concentration-versus-time curve (AUC; range, 93 to 224 mumol/L x hours), total body clearance (CI; range, 1,172 to 3,236 mL/min), or volume of distribution (range, 11.9 to 49.2 L) of FUra. Intrapatient data evaluation revealed a dose independent effect of rIFN-a. The mean FUra Css after rIFN-a administration (1.31 mumol/L) was greater than that before rIFN-a administration (1.02 mumol/L, P < .0001). FUra Cl after rIFN-a administration was reduced by 20% to 35% compared with use of FUra alone (P < .0001). Patients with a greater than 20% decrease in FUra Cl had a fourfold greater incidence of diarrhea. CONCLUSION: rIFN-a reduces FUra Cl and, consequently, increases FUra-associated toxicity. Phase II studies of FUra and rIFN-a seem to be warranted. PMID- 8478668 TI - Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia. AB - PURPOSE: Several placebo-controlled randomized clinical trials have demonstrated that megestrol acetate can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/d. METHODS: This trial randomized 342 assessable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800, or 1,280 mg/d. Patients were evaluated monthly by history, examination, patient-completed questionnaires, and serum albumin levels. RESULTS: The data demonstrate that there is a positive dose response effect for megestrol acetate on appetite stimulation (P < or = .02). In concert, there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. CONCLUSION: The positive dose-response effect that we observed for megestrol acetate on appetite stimulation supports both our prestudy hypothesis and other available literature. Nonetheless, based primarily on the cost and inconvenience associated with the use of higher doses of this drug, it is reasonable to use 160 mg/d for the initial treatment of cancer anorexia/cachexia in routine clinical practice. PMID- 8478669 TI - Postchemotherapy rheumatism. AB - PURPOSE: This report describes a previously unreported clinical phenomenon that occurs in some patients after completion of combination chemotherapy. METHODS AND RESULTS: Eight case reports are presented. Affected patients developed a syndrome of myalgias/arthralgias within several months of completing cyclophosphamide/fluorouracil (5FU)-containing adjuvant combination chemotherapy for breast cancer. These symptoms did not appear to be related to cancer recurrence or any common rheumatologic disorder. The syndrome generally resolved over several months. CONCLUSION: Postchemotherapy rheumatism is a syndrome of myalgias/arthralgias that usually develops 1 to 3 months after completion of adjuvant chemotherapy. Recognition of this syndrome can limit the need for extensive work-ups to exclude recurrent breast cancer or inflammatory rheumatologic diseases. PMID- 8478670 TI - The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women. AB - PURPOSE AND METHODS: We used decision analysis to model the natural history of breast cancer in hypothetical cohorts of 45-year-old women receiving tamoxifen, chemotherapy, or combined therapy. We used recurrence and efficacy data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), utility values from focus groups, and costs from clinic charges and Medicare data. RESULTS: Tamoxifen alone provides minimal benefit in estrogen receptor-negative (ER-; 0.2 to 0.4 months) and modest benefit in receptor-positive (ER+; 3.5 to 5.2 months) cancer. Chemotherapy adds substantial benefit independent of receptor status (4.9 to 10.7 quality-adjusted months). In ER+ cancer, combined therapy adds an additional benefit (1.2 to 2.1 months) compared with chemotherapy alone. The incremental costs (United States dollars) necessary to add an additional year of life to the average woman ranged from $4,300 to $11,400 for tamoxifen alone for ER+ cancer, $4,900 to $11,400 for chemotherapy alone, and $14,800 to $33,100 for combined therapy. CONCLUSION: In premenopausal early-stage breast cancer, chemotherapy adds substantial clinical benefit at a modest cost. Tamoxifen alone adds meaningful benefit only in ER+ cancer. Combined therapy is effective for all women, but is most beneficial and only cost-effective in ER+ women. If secondary effects of tamoxifen in reduction of cardiovascular and osteoporosis mortality are confirmed, then combined treatment may be optimal for all premenopausal women. PMID- 8478671 TI - Should the elderly receive chemotherapy for node-negative breast cancer? A cost effectiveness analysis examining total and active life-expectancy outcomes. AB - PURPOSE: This study determines the survival benefit and cost-effectiveness of adjuvant chemotherapy in elderly women with breast cancer. In addition, the analysis measures the impact of substituting active life expectancy for survival in the clinical decision. PATIENTS AND METHODS: Two cohorts of women with estrogen receptor (ER)-negative, stage I breast cancer from age 60 to 80 years were monitored using a Markov process. One group received standard chemotherapy following primary therapy, and the other had no postoperative treatment. Data were derived from recently published clinical trials and a major meta-analysis. Outcome included the average survival, active life-expectancy, and incremental cost/quality-adjusted life-year (cost/QALY). RESULTS: Adjuvant chemotherapy prolongs survival in older women, but to a lesser extent compared with younger women. The average gain in quality-adjusted months was 1.8 months in a 75-year old cohort at a cost/QALY of $4,400. These small benefits were not substantially altered when univariate changes were made in toxicity, recurrence risk, or effectiveness of chemotherapy. When active life expectancy replaced survival as an end point, the benefit for 75-year-old women decreased to 2 weeks at a cost of more than $96,000/QALY. CONCLUSION: There is a small survival benefit for adjuvant chemotherapy in elderly patients. The cost of this benefit is high, but within the range of commonly reimbursed procedures until a point between 75 and 80 years old. The use of active life expectancy as the primary outcome reduces the benefit and adds to the cost. If physicians and policymakers agree that active life expectancy is a relevant outcome, withholding chemotherapy for patients > or = 70 years old is a reasonable approach. PMID- 8478672 TI - Characteristics of women at risk for psychosocial distress in the year after breast cancer. AB - PURPOSE: To provide a detailed description of rehabilitation problems of women, considered to be low risk and at risk for psychosocial morbidity, diagnosed with stage I and II breast cancer 1 month and 1 year after primary treatment. PATIENTS AND METHODS: A sample of 227 newly diagnosed breast cancer patients were systematically interviewed by a clinical social worker and classified for risk of psychosocial distress in the year after diagnosis. They completed a battery of standardized instruments to assess quality of life (QL), rehabilitation needs, and psychologic distress. The primary QL instrument, the Cancer Rehabilitation Evaluation System (CARES), provides a detailed listing of rehabilitation needs. Descriptive CARES data are presented with comparisons between the two groups. RESULTS: The at-risk women had significantly more problems with greater severity than the low-risk women in all areas (physical, psychosocial, medical interaction, sexual, and marital). While both groups showed improvement over the year following diagnosis, the at-risk group had significantly more problems 1 year later. Many physical problems subside, but problems at the local surgical site, psychologic distress, communication with marital partners, and negative body image are more persistent in the at-risk group 1 year later, while half of both groups continue to have sexual dysfunction. CONCLUSION: The detailed listing of problems provided by the CARES may be helpful to clinicians in their interactions with patients. The need for preventive and early intervention for the at-risk patients is underscored. PMID- 8478673 TI - Using the tolerable-dose diagram in the design of phase I combination chemotherapy trials. AB - PURPOSE: Choosing maximum-tolerated doses (MTDs) of agents to be administered in combination is more complicated than choosing the MTD for a single agent. This is because there are many combinations of doses that will be tolerated. We offer guidance in targeting specific MTD combinations, and suggest trial designs to achieve these targets. METHODS: A graphical method based on a simple, previously described mathematical model is used to guide the phase I trial design. The method involves constructing a tolerable-dose diagram, which displays the toxicities that are expected to occur at various dose combinations. The data required for the method are the single-agent toxicity profiles of the agents. Designs for combinations of taxol with fluorouracil, carboplatin, doxorubicin, cyclophosphamide, and cisplatin are used to demonstrate the methods. RESULTS: For all of the drugs considered here, leukopenia is dose-limiting or nearly dose limiting. Consequently, no major improvement in total dose-intensity is achievable by combining these drugs. If leukopenia can be eliminated or substantially reduced by use of chemoprotective agents, then a cyclophosphamide/taxol combination appears promising from a dose-intensity point of view. For other combinations, the doses must be reduced from single-agent MTD levels. In the absence of biologic information such as concentrations needed for optimal modulation, it is suggested that single-agent MTDs be reduced approximately proportionately for each drug in the combination. CONCLUSION: Tolerable-dose diagrams are useful for planning phase I trials of combinations of agents. They can suggest which combinations are promising from a dose-intensity perspective, as well as dose-escalation schemes for combinations to be pursued for dose-intensity or other considerations. PMID- 8478674 TI - Intermediate lymphocytic lymphoma: clinical and pathologic features of a recently characterized subtype of non-Hodgkin's lymphoma. AB - PURPOSE: We present a comprehensive review of clinical, pathologic, molecular, and prognostic features and therapy of intermediate lymphocytic (mantle cell) lymphoma (ILL/MCL), a recently characterized subtype that represents 2% to 8% of non-Hodgkin's lymphomas (NHLs), but which has not been included in most classification schemes, including the International Working Formulation. DESIGN: The English-language literature encompassing the above aspects, published between 1977 and 1992, is critically reviewed. RESULTS AND CONCLUSION: ILL/MCL is a disease of proliferating B lymphocytes that is characterized by generalized lymphadenopathy and frequent, often extensive, involvement of the spleen, bone marrow, and gastrointestinal tract. The malignant cells usually express the markers CD5 and IgM with or without IgD, but not CD10, on the cell surface, and grow in one of two dominant histologic patterns: mantle zone and diffuse. The characteristic cytogenetic abnormality is a t(11;14)(q13;q32) translocation, which juxtaposes the bcl-1 locus on chromosome 11 with the immunoglobulin (Ig) heavy-chain locus on chromosome 14, and appears to result in dysregulated expression of the gene encoding cyclin D1. Median survival is in the range of 2 to 5 years. While responses to chemotherapy may be seen in up to half the patients, relapses are the rule, and longterm survival is uncommon. The optimal treatment remains undefined, although therapy may be deferred until there are symptoms or complications, at which time judicious administration of alkylating agents and glucocorticoids may result in effective palliation. PMID- 8478675 TI - Follow-up report on the outcome of patients relapsing after autologous marrow transplantation for malignant lymphoma. PMID- 8478676 TI - Effects of posterior association cortex lesions on brain potentials preceding self-initiated movements. AB - To assess the role of subregions of the posterior association cortex in movement control, we recorded movement-related potentials (MRPs) in patients who had lesions centered in the temporal-parietal junction (T-PCx; damaged areas 22, caudal 39, 40, and 42; n = 7), superior parietal cortex (ParCx; damaged areas 5, 7, rostral 39, and 40; n = 5), and posterior association cortex lesions involving both the temporal-parietal junction and the superior parietal structures (PosCx; damaged areas 7, 22, 39, 40, 41, and 42; n = 5) and in 14 age-matched normal controls. MRPs were recorded in a self-paced button-press task in which subjects performed a switch closure with the right, left, or both hands (experiment I, experiment II, and experiment III, respectively) under counter-balanced experimental conditions. Data epochs beginning 1400 msec prior to and extending to 600 msec after each motor response were recorded from scalp sites over the precentral, central, and parietal regions. Normal controls and patients with T PCx lesions generated comparable vertex maximal, symmetrical readiness potentials (onset 1000 msec), contralaterally enhanced NS' values (onset 500 msec), and MP values (onset 100 msec) preceding voluntary self-paced movements. Extensive lesions involving the posterior association cortex reduced MRP amplitudes. Patients with selective ParCx lesions also had marked reduction of MRPs under all experimental conditions. The MRP findings coupled with clinical and behavioral data on patients with parietal-cortex lesions indicate that the superior parietal regions are part of a neural system necessary for movement preparation. PMID- 8478677 TI - Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat. AB - Neuronal protein synthesis is severely depressed following stress such as heat shock, hypoxia, and hypoglycemia. Following reversible cerebral ischemia, protein synthesis is transiently inhibited in ischemia-resistant areas, but persistently depressed in vulnerable brain regions. Eukaryotic initiation factor 2 (eIF-2) activity, that is, the formation of the ternary complex eIF-2.GTP.initiator 35S Met-tRNA, a rate-limiting step in the initiation of cellular protein synthesis, was studied in the rat brain during and following 15 min of transient global cerebral ischemia. At 30 min and 1 hr of reperfusion, a general decrease of eIF-2 activity by approximately 50% was seen in the postmitochondrial supernatant (PMS). In the relatively resistant neocortex and CA3 region of the hippocampus, the eIF-2 activity returns to control levels at 6 hr of reperfusion, but remains depressed in the vulnerable striatum and the CA1 region. Similarly, the activity of the guanine nucleotide exchange factor (GEF), which catalyzes the exchange of GTP for GDP bound to eIF-2, a crucial step for the continued formation of the ternary complex, is transiently reduced in neocortex but persistently depressed in striatum. The postischemic decrease in eIF-2 activity is further attenuated by agarose-bound alkaline phosphatase, and mixing experiments revealed that a vanadate-sensitive phosphatase may be responsible for the depression. Addition of partially purified GEF to PMS from postischemic neocortex restored eIF-2 activity to control levels. We conclude that ischemia alters the balance between phosphorylation and dephosphorylation reactions, leading to an inhibition of GEF and a depression of ternary complex formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478678 TI - The contributions of protein kinase A and protein kinase C to the actions of 5-HT on the L-type Ca2+ current of the sensory neurons in Aplysia. AB - In the sensory neurons of Aplysia, 5-HT acts through cAMP to reduce current flow through two classes of K+ channels, the S-K + channel and a transient K+ channel (Ikv). In addition, 5-HT increases a voltage-dependent, nifedipine-sensitive Ca2+ current. In this article we show that, while the effect on the S-K+ channel is mediated exclusively by cAMP, the effect on the Ca2+ current can be mimicked by phorbol 12,13-dibutyrate (PDBu) as well as by intracellular injection of cAMP. We then use specific blockers of protein kinase C (PKC) and the cAMP-dependent protein kinase A (PKA) to examine the roles of PKC and PKA in mediating the effect of 5-HT on the nifedipine-sensitive Ca2+ current. We find that H-7, a kinase inhibitor that appears to inhibit PKC more effectively than PKA in intact Aplysia neurons, reverses the increase in the Ca2+ current produced by PDBu. Moreover, H-7 partially blocks the effect of 5-HT on the Ca2+ current without affecting the decrease in the S-K+ current. A more specific PKC inhibitor (the 19 31 pseudosubstrate of PKC) also partially blocks the increase in the Ca2+ current produced by 5-HT, suggesting that this increase is mediated by PKC. Rp-cAMPS, a specific blocker of PKA, did not block the increase in the Ca2+ current produced by 5-HT, suggesting that the effect of 5-HT on this current may be mediated to only a small extent by PKA. The effect of 5-HT on the S-K+ current and the Ca2+ current can also be separated on basis of the time course of their appearance. The fact that the decrease in the S-K+ current precedes the increase in Ca2+ current suggests that there may be a temporal difference in the activation of the two kinase systems. PMID- 8478679 TI - A higher control center of locomotor behavior in the Drosophila brain. AB - In order to elucidate the behavioral significance of the central complex (CC), we have examined walking in 15 Drosophila mutant strains belonging to eight independent X-linked genes that affect the structure of the CC. Compared to four different wild-type strains, all are impaired either in a general or in a paradigm-dependent manner. Behavioral deficits concern walking activity, walking speed, or "straightness of walking" as measured in an object fixation task, in fast phototaxis, and in negative geotaxis. Behavioral deficits of three strains with mutations in different genes were studied in detail using mosaic analysis and high-speed cinematography. In all cases the focus for declining walking activity is located in the brain and is fully correlated with the respective defect of the CC. A high correlation between the degree of the behavioral impairment and the severity of the structural defect in two strains further adds to the evidence. Declining walking activity is not an unspecific side effect of structural brain defects, as steady walking is observed in structural mutants of the visual system and mushroom bodies. In mutant flies no-bridgeKS49 (nob), step size as a function of the stepping period is reduced. The focus of the resulting reduced average and maximum walking speeds resides in the brain and, again, the behavioral impairment fully correlates with the structural defects of the CC. While no indication is found for a role of the CC in setting up the basic stepping rhythm in straight walking (a respective phenotype in mutant central complexKS181 flies resides in the ventral ganglion), a role in turning and start/stop maneuvers is suggested by aberrations in the stepping pattern of nob flies during such episodes. PMID- 8478680 TI - The jamming avoidance response in Eigenmannia is controlled by two separate motor pathways. AB - The gymnotiform fish Eigenmannia generates weakly electric signals for electrolocation and communication. The signals are produced by electric organ discharges (EODs) that are driven by a medullary pacemaker nucleus. To avoid jamming by neighboring conspecifics with similar frequencies, a fish raises its own EOD frequency if the neighbor's frequency is lower, and it lowers its EOD frequency if the neighbor's frequency is higher (Watanabe and Takeda, 1963). Both the raising and lowering of EOD frequency of this jamming avoidance response (JAR; Bullock et al., 1972) are thought to be controlled by feature-extracting neurons in the diencephalic prepacemaker nucleus (PPn-G) that discriminate the sign of the frequency difference between the jamming signal and the fish's EOD (Kawasaki et al., 1988a; Rose et al., 1988; for review, see Heiligenberg, 1991). These prepacemaker neurons are excited in response to lower jamming frequencies, thereby raising the frequency, and inhibited by higher jamming frequencies, producing a discharge deceleration. The results of experiments presented here, however, suggest a mechanism for the motor control of the JAR that is different from the one described previously (see, e.g., Heiligenberg, 1991). Two prepacemaker nuclei, one PPn-G and one sublemniscal prepacemaker nucleus (SPPn) (Keller et al., 1991 a,b), which provide the only known inputs to the pacemaker, were lesioned selectively. This article explores the effects of these lesions on the JAR. Pharmacological experiments were used to elucidate the transmitter types involved. The results suggest that the JAR is controlled by two separate motor pathways. One controls frequency rises and originates in the dorsal substructure of the nucleus electrosensorius (Keller, 1988). It sends excitatory connections to the diencephalic prepacemaker and finally to the pacemaker nucleus, where AMPA type receptors mediate the synaptic transmission. The second pathway controls frequency decreases and originates in the ventral substructure of the nucleus electrosensorius. It provides GABAergic input to the SPPn. The SPPn is tonically active and also controls the EOD frequency even in the absence of jamming signals. Its projection to the pacemaker nucleus is mediated by NMDA-type receptors. The results of this study suggest that there is no single population of final, feature-extracting elements or "recognition units" that controls JAR related shifts of the pacemaker frequency. Instead, the motor control of the JAR consists of an interaction of two independent pathways according to a "push-pull" principle. PMID- 8478681 TI - Gangliosides rescue neuronal cells from death after trophic factor deprivation. AB - Serum-free cultures of PC 12 cells have been used as a model system for studying neuronal death occurring after neurotrophic factor deprivation. In this system, NGF rescues cells from death and prevents apoptotic DNA fragmentation. We report here that GM1 also promotes long-term survival of naive and NGF-pretreated PC 12 cells in serum-free medium and prevents internucleosomal cleavage of PC 12 cell DNA. In contrast to NGF, GM1 does not promote neurite outgrowth or somatic hypertrophy. The survival effects of GM1 are concentration dependent, with maximal activity at 30-50 microM. Optimal promotion of survival is obtained with multiple additions of GM1. Asialo-GM1 and sialic acid do not mimic these actions, indicating a requirement for the intact GM1 molecule. Prevention of serum-free PC 12 cell death is also obtained with di-, tri-, and tetrasialogangliosides. The ganglioside effects on survival and DNA fragmentation appear to be independent of macromolecular synthesis. GM1 is also effective under conditions in which cellular protein kinase C activity is downregulated by preexposure to high concentration of 12-O-tetradecanoylphorbol-13-acetate. Furthermore, GM1 promotes long-term survival of cultured rat sympathetic neurons after withdrawal of NGF. These findings complement prior observations that gangliosides protect cerebellar granule neurons from neurotoxicity caused by exposure to excitatory amino acids and extend the actions of gangliosides to rescue of neuronal cells deprived of neurotrophic factor support. PMID- 8478682 TI - Expression of glutamate receptor genes in the mammalian retina: the localization of GluR1 through GluR7 mRNAs. AB - Seven distinct cDNAs encoding functional subunits of the AMPA/kainate-type glutamate receptors have been recently cloned. This in situ hybridization study was done to determine which subunits are expressed in the retina and, where possible, which neurons express them. Hybridization of 35S-UTP-labeled cRNA probes with transverse sections revealed that mRNAs for all seven receptor subunits (GluR1-GluR7) are expressed in both cat and rat retinas. GluR1 and GluR2 produced labeling over the entire inner nuclear layer (INL) and ganglion cell layer (GCL). GluR3-GluR7 have more limited distributions, indicative of expression by only a subset of neurons. All of the subunits are expressed by the cells at the inner edge of the INL, where amacrine cells reside, yet the layers with the horizontal, bipolar, and ganglion cells contain different subsets of subunits. These findings suggest that these glutamate receptor subunits are employed at many of the retinal synapses, including the photoreceptor input to the outer plexiform layer and the bipolar cell's contacts with the processes at the INL. It is also possible that some glial cells in the INL express some of the subunits. Since different combinations of GluR1-GluR3 have been shown to play an important role in the calcium permeability in response to glutamate, we investigated whether single cells coexpressed those subunits. By hybridizing adjacent semithin (1 micron) sections of the cat retina with probes for GluR1 GluR3, it was possible to observe coexpression of all three subunits, or of pairs of these subunits, in cells within the INL and GCL. PMID- 8478683 TI - An audio-vocal interface in echolocating horseshoe bats. AB - The control of vocalization depends significantly on auditory feedback in any species of mammals. Echolocating horseshoe bats, however, provide an excellent model system to study audio-vocal (AV) interactions. These bats can precisely control the frequency of their echolocation calls by monitoring the characteristics of the returning echo; they compensate for flight-induced Doppler shifts in the echo frequency by lowering the frequency of the subsequent vocalization cells (Schnitzler, 1968; Schuller et al., 1974, 1975). It was the aim of this study to investigate the neuronal mechanisms underlying this Doppler shift compensation (DSC) behavior. For that purpose, the neuronal activity of single units was studied during spontaneous vocalizations of the bats and compared with responses to auditory stimuli such as playback vocalizations and artificially generated acoustic stimuli. The natural echolocation situation was simulated by triggering an acoustic stimulus to the bat's own vocalization and by varying the time delay of this artificial "echo" relative to the vocalization onset. Single-unit activity was observed before, during, and/or after the bat's vocalization as well as in response to auditory stimuli. However, the activity patterns associated with vocalization differed from those triggered by auditory stimuli even when the auditory stimuli were acoustically identical to the bat's vocalization. These neurons were called AV neurons. Their distribution was restricted to an area in the paralemniscal tegmentum of the midbrain. When the natural echolocation situation was stimulated, the responses of AV neurons depended on the time delay between the onset of vocalization and the beginning of the simulated echo. This delay sensitivity disappeared completely when the act of vocalization was replaced by an auditory stimulus that mimicked acoustic self stimulation during the emission of an echolocation call. The activity of paralemniscal neurons was correlated with all parameters of echolocation calls and echoes that are relevant in context with DSC. These results suggest a model for the regulation of vocalization frequencies by inhibitory auditory feedback. PMID- 8478684 TI - Development of local circuits in human visual cortex. AB - How we see the world largely depends on the organization of neuronal circuits in visual cortex. Physiological recordings in mammals indicate that circuits develop over a period that extends well into early postnatal ages (LeVay et al., 1980; Albus and Wolf, 1984). Our understanding of how these circuits are assembled during development is still fragmentary (Katz and Callaway, 1992). Here we describe the development of local connections within visual cortex, using the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate to trace axonal projections in post-mortem human brains. Vertical (intracolumnar) connections between layers 2/3 and 5, which link neurons representing the same point in the visual field, develop prenatally at 26-29 weeks gestation. In contrast, horizontal (intercolumnar) connections between different points in the visual field develop later. They first emerge prenatally at approximately 37 weeks gestation within layers 4B and 5. After birth (> 40 weeks gestation) the fiber density increases rapidly, showing a uniform plexus of connections at 7 weeks postnatal. The more adult-like patchiness of the projection, however, emerges after 8 weeks postnatal. Long-range horizontal connections within layer 2/3 develop after the connections within layers 4B, 5, and 6. These connections emerge after 16 weeks postnatal, long after cytochrome oxidase blobs have developed, and reach mature from sometime before 15 months of age. Unlike the patchy horizontal projections within layers 4B and 5, which seem to develop through a process of collateral elimination, long-range projections within layer 2/3 are patchy from the outset and seem to develop with greater topographical precision. The finding that intracolumnar connections develop before intercolumnar projections suggests that circuits that process local features of a visual scene develop before circuits necessary to integrate these features into a continuous and coherent neural representation of an image. In addition, the sequential development of horizontal connections within layer 4B before those within layer 2/3 suggests that circuits that may be related to the processing channel for visual motion develop in advance of those that may be more intimately related to the processing of form, color, and precise stereoscopic depth. PMID- 8478685 TI - Pharmacology of the effects of bradykinin, serotonin, and histamine on the release of calcitonin gene-related peptide from C-fiber terminals in the rat trachea. AB - The effects of inflammatory substances, bradykinin (BK), 5-HT, and histamine (HIS), on the release of calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory afferents in the rat trachea were examined ex vivo. With intralumenal perfusion, the isolated rat trachea displays low but measurable secretion of CGRP (32 +/- 4.6 fmol/10 min fraction). The addition of BK (10(-6) to 10(-4) M) to the superfusate resulted in an immediate, concentration-dependent increase in the level of CGRP (5-30-fold increase above baseline) in the perfusates, and this effect showed a concentration-dependent tachyphylaxis. [Des-Arg10]-kallidin, a B1 receptor agonist, at concentrations of up to 10(-4) M did not induce any significant increase in CGRP outflow from the rat trachea. HIS at 10(-4) M caused a modest but progressive augmentation in the release of CGRP. 5-HT at 10(-4) M had no effect upon the resting efflux of CGRP, but at a concentration of 10(-6) M significantly enhanced the release of CGRP evoked by capsaicin (10(-6) M). Similar conditioning studies carried out with HIS and BK showed no augmentation. BK-evoked CGRP efflux was significantly inhibited by [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK (B2 antagonist) and indomethacin. While [Des Arg9, Leu8]-BK (B1 antagonist) also caused a reduction of BK-induced release, its effect did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8478686 TI - Effects of met-enkephalin on GABAergic spontaneous miniature IPSPs in organotypic slice cultures of the rat hippocampus. AB - The action of met-enkephalin on GABAergic spontaneous miniature IPSPs (smIPSPs) was investigated in CA1 neurons from hippocampal slice cultures. In the presence of excitatory amino acid blockers (2,3-dihydroxy-6-nitro-7-sulphamoyl benzo(F)quinoxaline, DL-2-amino-5-phosphonovaleric acid) and TTX, a continuous high-frequency bombardment of smIPSPs was recorded. The smIPSPs were blocked by the GABAA antagonist bicuculline. The occurrence of the smIPSPs was random and their amplitude distribution was skewed toward larger smIPSPs. Met-enkephalin (10 20 microM) reversibly reduced the frequency and changed the amplitude distribution of the smIPSPs. The proportion of "large" smIPSPs was reduced, but a loss of "small" smIPSPs also contributed to the reduction in smIPSP frequency. The selective mu-receptor agonist DAGO mimicked the effect of met-enkephalin and naloxone blocked the effect of DAGO. Hyperpolarization of the neuronal membranes, produced by reducing the extracellular K+ concentration, did not reduce the frequency of the smIPSPs, nor did it block the effect of DAGO. Reduction of the extracellular concentration of Ca2+ combined with an increase in extracellular Mg2+ or the addition of Cd2+ did not reduce the smIPSP frequency, nor did it block the effect of DAGO. These results suggest that CA1 pyramidal cells of hippocampal organotypic cultures are tonically inhibited by spontaneous release of GABA, through a release mechanism that is independent of propagated sodium action potentials. Met-enkephalin and DAGO reduce the tonic inhibition by reducing the frequency of the smIPSPs, through a direct action on the presynaptic GABAergic terminals. The effect was probably not mediated by hyperpolarization of the presynaptic membrane or by modulation of presynaptic Ca2+ currents. PMID- 8478687 TI - Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression. AB - The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d tubocurarine. The most heavily labeled cells are GABA-containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input. PMID- 8478688 TI - Glutathione S-transferase isoenzymes in rat brain neurons and glia. AB - The glutathione S-transferases (GSTs) constitute a family of cytosolic isoenzymes and a structurally unrelated microsomal enzyme that is involved in the detoxication of electrophilic xenobiotics. These enzymes also participate in the intracellular binding and transport of a broad range of lipophilic compounds including bilirubin, and hormones such as the glucocorticoids and thyroid hormones. The present investigation demonstrates that GSTs are present in neurons of the brainstem, forebrain, and cerebellum. An isoenzyme-specific distribution of GSTs was found in cytoplasm, nuclei, and nucleoli. The regional and cellular distribution of cytosolic GSTs in the brain was studied by immunohistochemistry, spectrophotometric enzyme assay, and reverse-phase HPLC. Polyclonal antibody against microsomal GST was strongly reactive with Purkinje cells throughout the cerebellar cortex, and with neurons in the brainstem and hippocampus. Nuclei of Purkinje cells and of neurons in the brainstem, hippocampus, and cerebral cortex were immunopositive for alpha-class GST 1-1 (YaYa), whereas alpha-class GST 2-2 (YcYc) antibody was consistently immunoreactive with the nucleolus, but not with the nucleus or soma. All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels. Reverse-phase HPLC indicated that there were also substantial regional differences in the pattern of alpha-, mu-, and pi-class GST subunit expression. For example, the thalamus/hypothalamus had the highest GST activity and greatest concentration of total GST protein and mu-class GST subunit 6 (Yb3), whereas the brainstem had the greatest concentration of pi-class GST subunit (Yp). This regional variation in GST expression may be reflective of regional differences in cell populations. In cerebellar cortex, the concentration of mu-class GST subunit 4 (Yb2) was greatest in the flocculus and lowest in the vermis. This is of clinical interest because the pattern of expression of mu-class GST subunit 4 (Yb2) in the cerebellum coincides with the known regional susceptibility of this structure to degeneration after exposure to toxic or metabolic insults. The vermis is most susceptible to these insults, whereas the lateral lobes and flocculus are most resistant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478689 TI - Neurogenesis in adult canary telencephalon is independent of gonadal hormone levels. AB - Neurons generated in adulthood are found throughout the canary telencephalon. We are interested in the factors that control the rate of proliferation of stem cells that give rise to these new neurons. The rate of incorporation of newly generated neurons into vocal-control regions varies seasonally. This difference could reflect a higher rate of neurogenesis, a lower rate of cell death, or an altered migration. We examined the incidence of thymidine-labeled cells in the telencephalic ventricular zone of adult canaries as a function of variations in gonadal hormone levels. Adult female canaries maintained on a short-day photoperiod were anesthetized and gonadectomized. Four separate groups of birds received systemic exposure to either testosterone, estradiol, a combination of an anti-androgen and an inhibitor of estrogen synthesis, or nothing. All birds were also implanted with an osmotic minipump that released 3H-thymidine for 3 d and were killed 4 or 7 d following the onset of treatment. Analysis of autoradiograms revealed no differences between groups in the incidence of labeling within the ventricular zone either at the level of the anterior commissure or directly adjacent to the vocal-control nucleus HVC (higher vocal center). These results suggest that sex steroids do not regulate the rate of cell division in the ventricular zone. Seasonal differences in the incorporation of labeled cells into HVC may therefore be due to regulation of neurogenesis by photoperiodic factors other than gonadal steroids or to some other cellular mechanism, such as differential migration or survival of neurons. PMID- 8478690 TI - GABA shapes sensitivity to interaural intensity disparities in the mustache bat's inferior colliculus: implications for encoding sound location. AB - This study examined how GABAergic inhibition affected binaural properties of neurons in the mustache bat's inferior colliculus. Evaluations were made by documenting changes in acoustically evoked inhibition that occurred when GABAergic inputs were reversibly blocked by iontophoretic application of the GABAA antagonist bicuculline. We studied neurons sensitive to interaural intensity disparities (IIDs), since these are the principal cues animals use to localize high-frequency sounds. Neurons sensitive to these cues receive excitation from one ear and inhibition from the other ear, and are called EI neurons. Recordings focused on the EI region in the hypertrophied 60 kHz isofrequency contour, where the sensitivities of the EI cells to IIDs are systematically ordered, thereby creating a map of IID sensitivity. EI neurons were classified on the basis of their IID functions, of which there were two principal types. Seventy percent of the cells had conventional IID functions where the firing rate evoked by a fixed intensity at the contralateral (excitatory) ear remained constant with low intensities at the ipsilateral (inhibitory) ear and then declined progressively as the intensity at the ipsilateral ear increased. We refer to cells that had this type of IID function simply as EI neurons. The IID functions in the remaining 30% of the cells showed binaural facilitation and were classified as EI/f neurons. In these cells, increasing sound intensity at the ipsilateral (inhibitory) ear when the intensity at the contralateral (excitatory) ear was fixed, initially caused the firing rate to increase by at least 25% above the rate evoked by the sound at the contralateral ear alone. Additional intensity increases at the ipsilateral ear then resulted in a marked decline in response rate. We examined the effects of bicuculline on three binaural properties: (1) the degree of inhibition evoked by the ipsilateral ear (the maximum inhibition), (2) the IID at which the unit's discharge rate declined by 50% (the 50% point), and (3) binaural facilitation. There are three main findings. First, bicuculline substantially reduced or eliminated the inhibition evoked by the ipsilateral ear in about 40% of the cells. In the other 60% of the cells, bicuculline had little or no effect on the magnitude of the ipsilaterally evoked inhibition. The second finding is that in more than half of the cells in which there was little or no reduction in the magnitude of the ipsilaterally evoked inhibition, bicuculline changed the IID at which the ipsilaterally evoked inhibition caused the discharge rate to decline by 50%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478691 TI - Number, distribution, and morphology of retinal ganglion cells with axons regenerated into peripheral nerve graft in adult cats. AB - The optic nerve of adult cats was transected and an autologous peripheral nerve was transplanted to the stump. Two months later retinal ganglion cells (RGCs) that had regenerated their axons were retrogradely labeled with fluorescent dye injected into the graft. The more than 4000 labeled cells, which were 3.0-4.3% of total ganglion cell number in the intact retina, were distributed in a high density area elongating horizontally, in a pattern similar to that observed in the intact retina. The dendritic morphology of RGCs with regenerated axons was examined after intracellular injections of HRP or Lucifer yellow in vitro. The morphology of alpha- and gamma-cells appeared comparable to normal, whereas the dendrites of some beta-cells seemed to degenerate. Some "unclassified" cells could not be identified as alpha-, beta-, or gamma-cells. The main dendrites of most unclassified cells were thin and less ramified than alpha- and beta-cells. Some unclassified cells had a vacant area in their dendritic fields, suggesting degenerative change in dendrites. The distal dendrites of some unclassified and gamma-cells had many fine processes that probably regrew during axonal regeneration. The proportion of alpha-, beta-, and other cells including gamma- and unclassified cells in the regenerating cell population was evaluated by examining all of the Lucifer yellow-injected cells in local patches. The average proportion of alpha-cells was 23.9%, about six times higher than in intact retinas. The average proportion of beta-cells was 50.3%, slightly higher than in intact retinas. The remaining cells (25.7%) could not be categorized as alpha or beta; this proportion is about half that found in intact retinas. These findings suggest that alpha-cells have the highest capacity to regenerate their axons into nerve grafts, rather than all types equally regenerating their axons. PMID- 8478692 TI - Functional uncoupling of inhibitory interneurons plays an important role in short term sensitization of Aplysia gill and siphon withdrawal reflex. AB - Attempts to explain learning-associated potentiation of synaptic transmission in model systems such as withdrawal reflexes in the mollusk Aplysia or the hippocampus of vertebrates have focused on the mechanisms by which transmitter release is increased in the principal elements of the circuit. Increased transmission in neuronal networks such as the gill and siphon withdrawal reflex (GSWR) of Aplysia may, however, also be caused by a decrease of transmitter release by inhibitory interneurons. The importance and function of cholinergic inhibitory transmission in the GSWR network were investigated. Central application of the nicotinic cholinergic antagonist d-tubocurarine (d-TC) considerably potentiated gill contractions, evoked either by nerve stimulation or by tactile stimulation of the siphon. Compound EPSPs evoked in motoneurons upon siphon nerve stimulation were also significantly prolonged following application of d-TC, but were unaffected by hexamethonium, a blocker of excitatory ACh receptors in Aplysia. Recordings from excitatory interneurons showed that they received excitation followed by powerful inhibitory input upon stimulation of the siphon nerve. Application of d-TC completely blocked this rapid inhibition, thus prolonging the compound EPSPs evoked in the interneurons. These effects were obtained at a concentration of d-TC (100 microM) that almost totally blocked fast inhibitory cholinergic transmission, but was without effect on monosynaptic connections between sensory neurons and motoneurons of the reflex. Facilitation of (1) compound EPSCs in motoneurons and (2) evoked excitatory interneuronal firing was reduced in preparations already disinhibited by pretreatment with d TC. Facilitation of sensory-motor synapses, however, was not reduced in the presence of d-TC, indicating that facilitatory interneurons are still activated under cholinergic blockade. These data show that transmission through the GSWR neuronal network is gated by a feedback inhibitory mechanism. They also suggest that a reduction of cholinergic inhibition onto excitatory interneurons may be a mechanism through which transmission within the GSWR network is increased during various forms of learning, such as sensitization. These data place new emphasis on the important role of inhibitory interneurons in determining the plastic properties of neuronal networks, in both invertebrates and vertebrates. PMID- 8478693 TI - Nerve growth factor-induced hyperalgesia in the neonatal and adult rat. AB - Recently, we have shown that the interaction between NGF and sensory neurons in early postnatal periods is restricted to nociceptive afferents (Ritter et al., 1991; Lewin et al., 1992a; Ritter and Mendell, 1992). Here we show that administration of excess NGF to neonatal or mature animals can lead to a profound behavioral hyperalgesia. Neonatal NGF treatment (postnatal day 0-14) resulted in a profound mechanical hyperalgesia that persisted until the animals had reached maturity (6 weeks of age). This hyperalgesia could be explained by an NGF mediated sensitization of A delta nociceptive afferents to mechanical stimuli. This peripheral sensitization wore off with a time course similar to that of the behavior hyperalgesia. Treatment of animals from the second postnatal week until 5 weeks of age (juveniles) led to a very similar behavioral hyperalgesia; however, there was no corresponding sensitization of A delta nociceptors to mechanical stimuli. Finally, one group of adult animals (5 weeks old) was treated daily with single injections of NGF for between 1 and 4 d. Within 24 hr after the first NGF injection these animals developed a mechanical hyperalgesia of the same magnitude seen after neonatal and juvenile NGF treatments. No sensitization of A delta nociceptive afferents was observed in these animals. In addition to the mechanical hyperalgesia, the animals also developed a heat hyperalgesia after one injection of NGF. The heat hyperalgesia was apparent within 15 min after the injection; however, signs of mechanical hyperalgesia were not seen until 6 hr after the injection. In conclusion, it appears that the NGF-induced mechanical hyperalgesia is brought about by different mechanisms in neonatal and adult rats. Furthermore, in adult animals the NGF-induced mechanical and heat hyperalgesia also appear to be attributable to two different mechanisms. The mechanical hyperalgesia may be due to central changes (see Lewin et al., 1992b), whereas the heat hyperalgesia is likely to result at least in part from the sensitization of peripheral receptors to heat. PMID- 8478694 TI - Sites of microtubule stabilization for the axon. AB - We have sought to determine the principal site(s) in the neuron where axonal microtubules (MTs) are stabilized. To accomplish this, we compared the proximal and distal regions of the axon and the axon shaft with regard to their content of newly stabilized MT polymer, using the following criteria. Stable polymer was identified by its resistance to nocodazole, and newly stabilized polymer was distinguished from older stable polymer by the staining of the former but not the latter for tyrosinated alpha-tubulin. Our results indicate that roughly 36.4%, 5.4%, and 2.4% of the total MT mass in the proximal and distal regions of the axon and the axon shaft is newly stabilized, respectively. Thus, while MT stabilization occurs throughout the axon, the proximal region is by far the most active with regard to this process. PMID- 8478695 TI - An invertebrate calcium-binding protein of the calbindin subfamily: protein structure, genomic organization, and expression pattern of the calbindin-32 gene of Drosophila. AB - Antisera against vertebrate calcium-binding proteins cross-react with Drosophila nervous and muscle tissue. We have used an antiserum against carp parvalbumin to isolate from a Drosophila head cDNA library immunopositive expression clones. Tissue in situ hybridization identified a clone that labeled specific neurons and muscles similar to the parvalbumin-like immunohistochemical staining pattern. Five independent cDNAs derive from an mRNA whose open reading frame codes for a 310 amino acid polypeptide. Sequence analysis identifies six EF-hand calcium binding domains and reveals 42% and 37% homology to chicken calretinin and calbindin D-28k, respectively. Since the positions of 9 out of 10 introns within the ORF are conserved from the Drosophila gene to both vertebrate genes, we conclude that we have identified the first invertebrate member of the calbindin sub-family of calcium-binding protein genes of the EF-hand homolog family. The calbindin-32 gene (cbn) maps to 53E on the second chromosome. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. The cloning of a Drosophila homolog to vertebrate neuronal Ca(2+)-binding proteins opens new routes to study the so far largely elusive function of these brain molecules. PMID- 8478696 TI - Short-term changes in the numerical density of synapses in the intermediate and medial hyperstriatum ventrale following one-trial passive avoidance training in the chick. AB - Previous ultrastructural studies using stereological counting techniques, based on assumptions regarding shape, size, and orientation of synapses, have suggested synaptic remodeling occurred at least 24 hr after one-trial passive avoidance training in day-old chicks. The present study estimates the mean synaptic density (Nv syn) in a region of the chick forebrain known to be involved in memory formation, the intermediate and medial hyperstriatum ventrale (IMHV), 1 and 24 hr following one-trial passive avoidance training. A stereological technique, the "disector," that makes no assumptions about size, shape, and orientation of synapses was used in the synaptic analyses. The density of axospinous synapses increased by approximately 77% at 1 hr posttraining in the right IMHV of chicks (M-trained) that learned to avoid a bitter-tasting bead, compared to those (W trained controls) that peck a water-coated bead. A measure of the postsynaptic density size, the mean projected height of synapses (H), was 57% smaller 1 hr posttraining in the right IMHV of M-trained chicks. These differences were not found at 24 hr posttraining. We suggest that structural modification of synapses may be a key part of the processes involved in short-term memory formation. PMID- 8478697 TI - G(olf) and Gs in rat basal ganglia: possible involvement of G(olf) in the coupling of dopamine D1 receptor with adenylyl cyclase. AB - Using specific antibodies and cDNA probes, we have investigated, in rat basal ganglia, the distribution and the regulation of the expression of the alpha subunits of Gs and G(olf), two GTP-binding proteins (G-proteins) that stimulate adenylyl cyclase. We confirmed that G(olf) alpha is highly expressed in caudate putamen, nucleus accumbens, and olfactory tubercle, whereas Gs alpha is less abundant in these areas than in the other brain regions. Intrastriatal injections of quinolinic acid decreased dramatically the levels of G(olf) alpha protein in the striatum and the substantia nigra, and those of G(olf) alpha mRNA in the striatum. Retrograde lesions of striatonigral neurons with volkensin reduced markedly the levels of D1 dopamine (DA) binding sites, as well as those of G(olf) alpha protein and mRNA in the striatum, without altering D2 binding sites. In contrast, both types of lesions increased the levels of Gs alpha protein in the striatum and substantia nigra. Immunocytochemistry showed the presence of G(olf) alpha protein in striatal medium-sized neurons and in several other neuronal populations. These results demonstrate that striatonigral neurons contain high levels of G(olf) alpha and little, if any, Gs alpha, suggesting that the coupling of D1 receptor to adenylyl cyclase is provided by G(olf) alpha. The levels of G(olf) alpha were five- to sixfold higher in the striatum than in the substantia nigra, indicating a preferential localization of G(olf) alpha in the somatodendritic region of striatonigral neurons and providing a basis for the low efficiency of D1 receptor coupling in the substantia nigra. Six weeks after 6 hydroxydopamine lesions of DA neurons, an increase in G(olf) alpha (+53%) and Gs alpha (+64%) proteins was observed in the striatum. This increase in G(olf) alpha levels may account for the DA-activated adenylyl cyclase supersensitivity, without change in D1 receptors density, that follows destruction of DA neurons. Fine regulation of the levels of G(olf) alpha in physiological or pathological situations may be a critical parameter for the efficiency of DA neurotransmission. PMID- 8478698 TI - Attenuation of hippocampal long-term potentiation by ethanol: a patch-clamp analysis of glutamatergic and GABAergic mechanisms. AB - Long-term potentiation of synpatic transmission (LTP) of the perforant path- dentate gyrus synapse is induced by 5 Hz, theta-like stimulation patterns. Such stimuli induce plasticity that is most likely driven by a decrease in synaptic inhibition (disinhibition) mediated by GABAB autoreceptors. In the present study, we demonstrate that LTP induced in this manner is completely antagonized by ethanol. In order to determine the site of ethanol inhibition of LTP induced by theta-like stimulation, we combined slice patch recordings with pharmacologic isolation of the individual glutamatergic and GABAergic synaptic currents. The present experiments revealed that ethanol inhibited NMDA receptor-mediated synaptic currents without potentiation of GABAA currents or attenuation of GABAB mediated fading of GABAA synaptic currents. These observations with ethanol contrasted with the actions of the water-soluble benzodiazepine midazolam, which strongly potentiated GABAA synaptic currents, reversed the effect of GABAB mediated fading of GABAA synaptic currents, and therefore blocked the resulting NMDA synaptic currents. These data indicate that the effects of ethanol on long term changes in synaptic strength in the rat hippocampal formation are due primarily to an action at the NMDA receptor-channel complex. PMID- 8478699 TI - Mallinckrodt Fellowship. Using anti-sense to predict chemotherapy resistance of tumors. PMID- 8478700 TI - Pioneer Award. Engineer and chemist honored for four decades of nuclear pioneering. PMID- 8478701 TI - Abersold Award. Nuclear chemistry's 'two Alans' share basic science award. PMID- 8478702 TI - Concordance of nutritive myocardial perfusion reserve and flow velocity reserve in conductance vessels in patients with chest pain with angiographically normal coronary arteries. AB - We have previously shown that myocardial perfusion can be quantified by positron emission tomography (PET) with 15O-labeled water (H2(15)O), as experimentally validated with radiolabeled microspheres in animal hearts. The purpose of our study was to determine whether myocardial nutritive perfusion reserve assessed with PET in human subjects was parallel to flow velocity reserve assessed in conductance vessels measured with intracoronary Doppler probes. We studied nine patients with chest pain and angiographically normal coronary arteries with intracoronary Doppler flow velocity assessments before and after administration of 16 micrograms of intracoronary adenosine. We also assessed myocardial nutritive perfusion with PET and H2(15)O before and after intravenous administration of dipyridamole (0.56 mg/kg). Perfusion reserve (the ratio of absolute values of myocardial perfusion after dipyridamole administration to perfusion at rest) estimated with PET (3.5 +/- 0.9 s.d.) correlated closely with flow velocity reserve (the ratio of hyperemic intracoronary flow velocity to flow velocity at rest) (3.5 +/- 1.2, r = 0.80, p < 0.01). Absolute values of perfusion assessed tomographically averaged 1.22 +/- 0.19 ml/g/min in patients at rest and 4.16 +/- 0.93 after dipyridamole administration. Our data indicate that noninvasive assessment of myocardial perfusion with PET provides results that parallel intracoronary Doppler flow velocity measurements. Because PET delineates nutritive perfusion throughout the heart in absolute terms, its use may facilitate detection of impaired coronary arterial function and enhance delineation of the efficacy of potentially therapeutic interventions in patients with chest pain and angiographically normal coronary arteries. PMID- 8478703 TI - Regional cerebral blood flow improves with treatment in chronic cocaine polydrug users. AB - Brain perfusion is abnormal in chronic cocaine users. To determine whether these perfusion abnormalities are reversible following treatment, we studied 10 cocaine dependent polydrug users with 99mTc-HMPAO SPECT 2 to 3 days after admission to an inpatient treatment facility and at 7 to 8 days and 17 to 29 days after abstinence from drugs. The patients also received buprenorphine, an opioid mixed agonist-antagonist, beginning 10 days after admission and continuing to the end of the study. Imaging began 10-15 min after injection of 99mTc-HMPAO (20 mCi) using an annular gamma camera system. MRI was performed during hospitalization using a 1.5 Tesla system. SPECT and MRI were merged and five axial SPECT slices centered at the level of the basal ganglia were selected for analysis. Activity ratios were derived for cortical regions relative to cerebellar activity and were corrected for linearity with respect to regional cerebral blood flow. The cortical regions were classified as abnormal (activity ratio < 0.6), borderline (0.6-0.72) and normal (> 0.72) based on the results of the first SPECT study. In abnormal zones, regional cerebral blood flow (rCBF) increased 11.0% +/- 9.0% at 7 to 8 days and 23.8% +/- 9.4% at 17 to 29 days after initiation of treatment. The increase in rCBF was 4.8% +/- 7.1% (7 to 8 days) and 11.1% +/- 8.0% (17 to 29 days) in borderline cortex and decreased 2.9% +/- 6.3% (7 to 8 days) and increased only 2.7% +/- 13.4% (17 to 29 days) in normal cortex. The increase in rCBF did not vary significantly by location. The perfusion defects observed in chronic cocaine polydrug users are partially reversible with short-term abstinence and buprenorphine treatment. PMID- 8478704 TI - Role of quantitative planar thallium-201 imaging for determining viability in patients with acute myocardial infarction and a totally occluded infarct-related artery. AB - We studied 57 patients with a recent infarction and an occluded infarct-related artery to test the hypothesis that the amount of 201Tl on delayed planar images correlates with the extent of viable myocardium after acute myocardial infarction. There was a significant (p < 0.001) correlation between mean 201Tl activity in the infarct zone and regional wall motion score in that zone both at baseline (r = -0.60, n = 57) and 1 mo after attempted angioplasty (r = -0.67, n = 48), with better function being associated with greater 201Tl uptake in the delayed images. There was no correlation between the number of segments showing redistribution and the wall motion score. We conclude that in patients with recent myocardial infarction and an occluded infarct-related artery, the average 201Tl activity within the infarct zone on delayed planar imaging correlates well with the extent of viable myocardium in that zone. The presence or absence of redistribution does not influence these results. PMID- 8478705 TI - Immediate thallium-201 reinjection following stress imaging: a time-saving approach for detection of myocardial viability. AB - Thallium-201 reinjection following 3-4-hr redistribution imaging improves the detection of viable myocardium but considerably prolongs the total investigation time. We compared the results of immediate 201Tl reinjection with 3-hr redistribution imaging in 120 consecutive patients who were evaluated for myocardial ischemia. Thallium-201 was reinjected immediately following the postexercise study. The images were acquired 1 hr later and reacquired at 3 hr redistribution. A total of 960 segments per imaging series were evaluated, of which 320 (33%) segments showed perfusion defects on the post-exercise images. On the 1-hr images, 220 (69%) segments demonstrated enhanced thallium uptake, 97 (30%) segments did not change and 3 (1%) segments showed reverse redistribution. Of the 100 (97 + 3) persistent defects, only 12 (4%) segments showed fill-in of 201Tl on 3 hr redistribution images. A total of 49 (15%) segments showed reverse redistribution. Defects on postexercise images were seen in 95 patients (79%) of whom 9 (10%) showed no change on immediate reinjection images. In only 1 (1%) patient was the diagnosis changed from myocardial necrosis to myocardial ischemia after analysis of the 3-hr redistribution images. These data indicate that immediate postexercise reinjection of 201Tl followed by 1-hr image acquisition may be superior to 3-hr redistribution imaging in identifying viable myocardium in patients evaluated for myocardial ischemia. This protocol eliminates the need for an additional series of 3-4-hr redistribution images and offers the advantages of reduced total imaging time, improved convenience for the patient and increased patient throughput. PMID- 8478706 TI - Thallium reinjection imaging: the search for an optimal protocol. PMID- 8478707 TI - Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities. AB - Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range. PMID- 8478708 TI - Normalized clearance-to-uptake slope ratio: a method to minimize false-positive diuretic renograms. AB - The success of diuretic renography in the evaluation of children with renal outflow tract obstruction has been hampered by a high incidence of false-positive and indeterminate results. The main causes of interpretative errors are collecting system dilatation and impaired renal function. In this prospective study, we introduce a parameter with the potential to overcome these two problems: the normalized slope ratio (SRn). This ratio is calculated from the division of the maximum renal clearance slope by the maximum renal uptake slope, both normalized to peak renal activity. Fifty-one children (94 renal units) were evaluated. Traditional parameters such as diuretic half-time and percentage of retention at 30 min showed specificities of 77% and 85%, respectively. However, the normalized clearance slope increased specificity to 94% and SRn further improved it to 98%. The SRn takes into account the renal uptake curve, whose slope is dependent on glomerular function, and thus may correct for renal dysfunction. It also differentiates obstructed from patent kidneys even in cases with significant collecting system dilatation. As shown by regression analysis, it is independent of collecting system size. We recommend the routine use of this parameter to reduce false-positive and indeterminate results of diuretic renograms. PMID- 8478709 TI - Radiation dose to positron emission tomography technologists during quantitative versus qualitative studies. AB - Positron emission tomography technologists were monitored with thermoluminescent dosimeters (TLDs) during qualitative and quantitative studies. Doses to technologists during specific tasks were also measured. The technologists received at least twice as much radiation during the quantitative as the qualitative studies. The average dose per study for qualitative studies was 0.017 mSv (1.7 mrem) shallow and 0.014 mSv (1.4 mrem) deep. The average dose per study for the quantitative studies was 0.05 mSv (5 mrem) shallow and 0.04 mSv (4 mrem) deep. The average dose per study was based on the TLD dose accumulated over studies conducted over four 2-mo and one 1-mo intervals. The dose incurred by the technologists each time they drew a radioactive dose was 0.002 mSv (0.2 mrem) shallow and 0.001 mSv (0.1 mrem) deep. The doses received during injection were 0.014 mSv (1.4 mrem) shallow and 0.007 mSv (0.7 mrem) deep. Doses received during blood sampling were 0.016 mSv (1.6 mrem) shallow and 0.014 mSv (1.4 mrem) deep. During quantitative studies, the technologist received a much greater dose than during its qualitative counterpart due to the blood sampling process and increased time in the room with the radioactive patient. PMID- 8478710 TI - In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. AB - The tumor cell uptake of three tracers that can be labeled with isotopes suitable for PET imaging--FDG, L-methionine and thymidine--were examined in vitro in a human ovarian carcinoma cell line (HTB77IP3) at varying times following 30 Gy 60Co irradiation and were compared to a nonirradiated control group. FDG, methionine and thymidine uptake per tissue culture well all increased following irradiation when compared to basal values, although to a much lower extent than the increases in uptake seen in a nonirradiated group. This increase in tracer uptake occurred despite a 6.25-fold decline in viable cell numbers. When examined per cell, FDG uptake per cell increased 9.77-fold, methionine 7.82-fold and thymidine 9.48-fold over basal levels from Day 0 to Day 12 following irradiation. Part of these increases may be due to giant cell formation and/or radiation repair processes that require energy, protein and DNA substrates. While the in vitro system differs from in vivo systems due to the absence of a blood supply in vitro, a lack of infiltrating leukocytes and other factors, our data suggest that early assessment of human adenocarcinoma response to radiotherapy by PET with these tracers may be complicated by this normal increase in tracer uptake postirradiation. Clearly, in this human cancer cell line, early radiation-induced cell death is not associated with an early decline in tumor cell uptake of FDG, methionine or thymidine. PMID- 8478711 TI - High accumulation of 2-deoxy-2-fluorine-18-fluoro-D-galactose by well differentiated hepatomas of mice and rats. AB - The potential application of 2-deoxy-2-[18F]fluoro-D-galactose for the detection and evaluation of hepatomas with PET was examined in mouse and rat liver tumor models. Biodistribution studies showed that uptake of this marker was high in well-differentiated, spontaneous hepatoma of C3H mice at almost 92% of the normal liver level. The uptake by well-differentiated Morris rat hepatoma (5123D) was relatively high and second to that of the C3H hepatoma. On the other hand, uptake values for poorly differentiated mouse hepatoma (MH129P), rat hepatomas (AH109A, AH272), mouse melanoma (B-16) and mammary carcinoma (FM3A) were very low and only 14%-18% of that in the normal liver. The results suggest that while well differentiated hepatomas maintain a high galactose metabolic activity, poorly differentiated hepatomas or other tumors lose this to a large extent. Consequently, this radiopharmaceutical can be used with PET for biochemical characterization of hepatomas and the differential diagnosis between hepatomas and other cancers. PMID- 8478712 TI - Changes in local cerebral glucose utilization in the awake rat during acute and chronic administration of ethanol. AB - Local cerebral glucose utilization (LCGU) was measured in 51 structures of the rat brain after acute and/or chronic oral administration of ethanol using the quantitative autoradiographic 2-deoxyglucose method. In the acute experiments, ethanol (3.2 g/kg) was administered via a gastric tube 110 min before the 2-deoxy D-[1-14C]glucose. The chronic pretreatment was performed using increasing concentrations of ethanol in the drinking water for a period of 20-24 days. The most striking effects on LCGU were seen in the inferior colliculus. Acute and acute plus chronic treatment with ethanol significantly decreased LCGU by 33% and 37%, respectively, whereas chronic treatment significantly increased LCGU by 25%. In general, acute administration of ethanol decreased LCGU in 16 brain structures, particularly of the auditory system. Chronic treatment, besides its effect on the inferior colliculus, only decreased LCGU in the internal capsule. Chronic plus acute administration of ethanol decreased LCGU significantly in 22 structures. It is concluded that an acute oral administration of ethanol has distinct and mainly depressive effects on the functional activity of several brain areas. Chronic administration is less effective. PMID- 8478713 TI - From the cradle to the grave: alcohol and its effects upon the brain. PMID- 8478714 TI - False-positive lymph nodes by radioimmunoguided surgery: report of a patient and analysis of the problem. AB - Preoperative administration of radiolabeled monoclonal antibody allows radioimmunoguided surgery with hand-held intraoperative detection devices. From a theoretical perspective, this technology may offer more knowledgable patient management and more complete resection of intra-abdominal cancer. False-positive examinations may seriously jeopardize the widespread application of this apparatus. Our experience with a patient with false-positive lymph nodes following administration of 125I-labeled B72.3 monoclonal antibody is reported. After careful histopathological analysis of five nodes thought to be false positive for cystadenocarcinoma, one lymph node was found to have a minute nidus of cancer. The cause of false-positive radioimmunoguided tests and their implications for the clinical use of this tool is discussed. We interpreted our data to suggest that tumor antigen-monoclonal antibody complexes processed in reactive lymph nodes, anatomically draining the malignant tissue, may cause false positive tests. PMID- 8478715 TI - Bronchogenic carcinoma mimicking metastatic thyroid carcinoma. AB - We present a case of a false-positive 131I scan in the follow-up of a patient with papillary thyroid carcinoma, which developed 24 yr after radiation therapy for Hodgkin's disease. In the primary evaluation of a neck mass, histology was typical for a papillary thyroid carcinoma and thyroglobulin staining was positive. After total thyroidectomy, 131I uptake was seen in the hilum and right lung. The initial interpretation of these foci as metastatic disease was not supported by the progressive clinical course despite radioiodine treatment. Hence, repeated bronchial brushings and cytology of the pleural effusion were obtained. These specimens were negative in thyroglobulin staining and positive for synoptophysin, a marker for small-cell bronchial carcinoma. Thereby a small to medium cell undifferentiated bronchial carcinoma was demonstrated, which apparently was actively taking up iodine. In conclusion, an atypical clinical course of a suspected metastatic thyroid carcinoma should lead to a reevaluation of the initial diagnosis to prevent an inappropriate therapeutic regimen. PMID- 8478716 TI - Indium-111-labeled leukocyte scintigraphy in a case of cutaneous sarcoidosis. AB - A 54-yr-old woman with cutaneous nodules showed accumulation of 67Ga- and 111In labeled leukocytes in skin nodules, bilateral pulmonary hilar lymph nodes and the right upper mediastinum. Biopsy of the skin nodule proved epithelioid cell granuloma with moderate lymphocyte infiltration peripherally consistent with sarcoidosis. Sarcoidosis is a potential pitfall in labeled leukocyte imaging, which is performed for detecting a febrile focus. PMID- 8478717 TI - Indium-111-leukocyte imaging in Gaucher's disease. AB - A 29-yr-old man with Gaucher's disease and fever of unknown origin underwent 111In-labeled mixed autologous leukocyte scintigraphy. Although no focus of infection was identified, the resulting images were most unusual and were characterized by massive hepatomegaly, lack of central marrow activity and extensive lymph node uptake of labeled leukocytes. All of these findings could be explained on the basis of the patient's underlying disease. Hepatomegaly and absent central marrow activity correlated with extensive infiltration of these organs by Gaucher cells, while the lymph node findings were attributed to the presence of extramedullary hematopoiesis. PMID- 8478718 TI - Radiation dose estimates for the carbon-14-labeled urea breath test. AB - The use of the 14C-urea breath test for diagnosis of Helicobacter pylori infection in gastric mucosa has gained widespread acceptance and utilization. In order to obtain regulatory approval for this procedure, new dose estimates were required. Previous radiation dose equivalent estimates for males only were based upon data published in 1975 for bicarbonate metabolism. Since that time, calculational techniques for dose estimation have been significantly improved and the organ masses of Reference Man updated. We have calculated dose estimates for males and females who test positive (HP+) and negative (HP-) for gastric H. pylori infection. Our results indicate that the urinary bladder wall receives the highest absorbed dose in all four of the above subject populations (HP- males = 0.14 mGy/MBq; HP- females = 0.19 mGy/MBq; HP+ males = 0.10 mGy/MBq; HP+ females = 0.14 mGy/MBq). Gonadal absorbed doses were similar to those previously estimated (testes < 0.065 mGy/MBq and ovaries < 0.084 mGy/MBq, respectively). PMID- 8478719 TI - Estimation of left ventricular mass and infarct size from nitrogen-13-ammonia PET images based on pathological examination of explanted human hearts. AB - The purpose of this study was to develop a technique to quantify left ventricular mass and infarct size in chronic ischemic heart disease from PET images based on correlation with pathological examination of explanted human hearts. Fourteen hearts from patients with cardiomyopathy who had 13N-ammonia scans prior to orthoptic heart transplantation were studied. Accurate estimation of the relative infarct size was possible in patients with a well-delineated, nearly transmural infarct (r = 0.93, y = 1.1x - 0.7, n = 11). Both absolute and relative infarct mass measurements on PET images correlated well with pathological measurements. We identified a population of patients with patchy interstitial or subendocardial scarring with globally reduced perfusion, for which the infarct size could not be estimated using the criteria derived for the patients with well-delineated infarcts. PMID- 8478720 TI - How can positron emission tomography help evaluate patients before and after heart transplantation? PMID- 8478721 TI - Functional mapping of flow and back-diffusion rate of N-isopropyl-p iodoamphetamine in human brain. AB - Iodine-123-labeled N-isopropyl-p-iodoamphetamine (IMP) has been reported to be an excellent tracer for mapping cerebral blood flow with single-photon emission computed tomography (SPECT). Clinical interpretation of these SPECT images, however, requires further understanding of the kinetics of IMP in the human brain. In order to evaluate the kinetic behavior of IMP in normal and diseased areas, we measured flow and back-diffusion rates with serial dynamic SPECT scans following an intravenous bolus injection of IMP using a multi-detector SPECT scanner. Arterial input function was determined by octanol extracted radioactivity of serial arterial blood samples. Average values for influx rate (K1) and back-diffusion rate (k2) were 0.43 ml/g/min and 0.014 min-1 in the normal cerebral cortex, 0.43 and 0.013 in the basal ganglia, 0.28 and 0.012 in the white matter and 0.48 and 0.016 in the cerebellar hemisphere. The partition coefficient (K1/k2 ratio) was 32.4 ml/g in the cerebral cortex, 35.3 in the basal ganglia, 24.7 in the white matter and 30.4 in the cerebellum. The K1-to-k2 ratio in the infarcted and ischemic regions as well as in the tumor was smaller than that of the normal cortex. Accurate measurement of local cerebral blood flow (LCBF) based on the microsphere model was possible only on the early SPECT images, but a relative pattern of LCBF can be assessed with SPECT images obtained within 1 hr after injection except for tumors. PMID- 8478722 TI - Validation of renal output efficiency as an objective quantitative parameter in the evaluation of upper urinary tract obstruction. AB - This is a preliminary study of the parameter, renal output efficiency (ROE), for the quantitation of furosemide (frusemide) response in diuresis renography. This is calculated by a technique independent of variations in uptake rate by the kidneys. Eleven healthy volunteers and 34 patients suspected of upper urinary obstruction were subjected to gamma camera studies using 99mTc-MAG3 and a standard protocol. Furosemide was given at 18 min after the study was started. The ROE was calculated in each kidney and the results were correlated with final diagnosis. The range of ROE in healthy individuals varied between 82% and 98% (mean = 91.6%); while obstructed kidneys showed significantly reduced values (p < 0.001) ranging between 30% and 76% (mean = 56%). In the diagnosis of urinary obstruction, the ROE has a sensitivity of 91%, specificity of 94% and accuracy of 94%. ROE complements conventional diuresis renography and provides better diagnostic yield in patients with impaired renal function. PMID- 8478723 TI - Scintigraphic evaluation of liver masses: cavernous hepatic hemangioma. AB - Hepatic cavernous hemangioma must be included in the differential diagnosis of any hepatic solid mass. It is the second most common neoplasm of the liver, following intrahepatic metastases. With the exception of giant or symptomatic HCH, it does not require specific intervention. The ability to diagnose HCH radiologically (Table 2) has significant clinical importance. When confronted with clinical data and a preliminary radiologic study suggestive of HCH, serial planar blood-pool scintigraphy (with SPECT if the lesion is < 3-4 cm) should probably be the initial diagnostic examination. In comparison to MRI, it is safer, less expensive and easier for some patients to tolerate. For small, deep seated lesions or those adjacent to the heart or large vessels, MRI is the preferred test. Dynamic CT is probably most useful in patients with normal renal function in whom optimal imaging of the extrahepatic abdomen is desired. If the etiology of an incidental hepatic mass suspected to be an HCH is still not evident after these studies, angiography or biopsy are the remaining options. As described, angiography is sensitive and relatively specific for HCH. Although percutaneous biopsy may be associated with increased risk of bleeding, fine needle biopsy has been shown to be safe for hemangiomas. However, fine-needle biopsy is more useful for confirming a suspected malignancy than for actually diagnosing hemangioma. PMID- 8478724 TI - Gallium-67 scintigraphy in tuberculous and nontuberculous infectious spondylitis. AB - Vertebral osteomyelitis is a difficult condition to diagnose clinically. A retrospective review of 21 cases of infectious spondylitis (6 tuberculous, 15 nontuberculous) confirmed the utility of 67Ga scintigraphy in imaging this process. Gallium-67 scans were positive at all sites of disease in this patient population. They anticipated the presence of spondylar infection in 23% of regions where radiographic abnormalities were originally lacking, while confirming a current and ongoing septic process at the other sites where vertebral destruction was already present on x-ray. Gallium-67 studies, as compared to the 99mTc-MDP bone scans, also provided important information as to the extent of disease by documenting the presence of eight paraspinal abscesses and the location of remote extraspinal foci of infection both in soft tissues and in bone. The relative merits of all radiologic imaging procedures are discussed. A diagnostic algorithm is also suggested. PMID- 8478725 TI - Tough choices: who is to make the call? PMID- 8478726 TI - Parametric images for quantitative measurements of regional myocardial blood flow in humans: a step in the right direction. AB - Choi et al. describe a useful method for producing parametric images of myocardial blood flow from dynamic PET 13N-ammonia images of the myocardium. The method is important because it provides a convenient vehicle for quickly displaying anatomically oriented information about absolute values of myocardial blood flow in humans. Absolute values of myocardial blood flow will enhance our ability to assess relative coronary flow reserve and will make it possible to noninvasively and routinely measure absolute coronary flow reserve. In addition, absolute measurements of myocardial blood flow will be useful in addressing important clinical problems, such as myocardial viability, stunning and hibernation. We look forward to the time when technical advances make it possible to obtain accurate parametric images not only of transmural but also endocardial epicardial distribution of blood flow. PMID- 8478727 TI - Lesion detection in neuroblastoma with iodine-131-MIBG. PMID- 8478728 TI - Functional imaging of peripheral vascular disease. PMID- 8478729 TI - Fluorodeoxyglucose, myocardial perfusion and myocardial cell death. PMID- 8478730 TI - Detection of cardiovascular infections with radiolabeled leukocytes. PMID- 8478731 TI - A 'city that reads' ... or breeds? PMID- 8478732 TI - Do fetal heart rates predict gender? PMID- 8478733 TI - Neonatal kidnapping. PMID- 8478734 TI - Oocyte donation and in vitro fertilization: the nurse's role with ethical and legal issues. AB - Oocyte donation has made pregnancy a realistic option for women who want to become pregnant yet are unable to produce viable, healthy eggs. This article reviews oocyte donation technology, discusses ways that donor programs can deal effectively with the legal and ethical issues involved, and describes the role of the in vitro fertilization nurse. PMID- 8478735 TI - The biophysical profile: antepartal assessment of fetal well-being. AB - The assessment of fetal well-being is a primary consideration for perinatal nurses. The biophysical profile is a clinical evaluation of the status of the fetus based on assessment of multiple discrete variables. This article describes current biophysical profile scoring systems, the physiologic basis of the fetal variables, and factors that may affect the variables. It also discusses issues related to future applications and refinement of the biophysical profile, as well as nursing implications of the technology. PMID- 8478736 TI - Prevention of HIV infection in women. AB - The number of HIV-infected women in the United States has continued to rise. Although risk-reducing behaviors such as condom use, partner selection, partner reduction, and safe sex practices have been identified, women continue to engage in high-risk activities. Nurses need to offer testing for HIV infection to all women. Education programs directed at the transmission and prevention of HIV infection also are needed. This article describes nursing strategies designed to incorporate primary, secondary, and tertiary prevention of HIV infection in women. PMID- 8478738 TI - Nipple feeding for preterm infants with bronchopulmonary dysplasia. AB - OBJECTIVE: To examine the influence of an infant's physical condition on nipple feeding practices and the contribution of the infant's age at complete nipple feeding to dietary intake and somatic growth outcomes. DESIGN: A retrospective, correlational study. SETTING: Two Level III nurseries. PARTICIPANTS: Records of 55 preterm infants with bronchopulmonary dysplasia. MAIN OUTCOME MEASURES: The infant's intake of kcal/kg on Day 1 of complete nipple feeding and the weight gain per day between complete nipple feeding and discharge. RESULTS: Gestational age and days on mechanical ventilation, continuous positive airway pressure, or supplementary oxygen influenced age at start and at completion of nipple feeding (p < .05). The infant's weight when nipple feeding was introduced was the primary determinant of age at introduction of nipple feeding (B = .50, p < .001). The physical condition variables did not influence the transition time from introduction of nipple feeding to complete nipple feeding. Neither the physical condition variables nor the feeding practice variables contributed to caloric intake. Weight gain between the time of complete nipple feeding and hospital discharge was less for infants who were on supplementary oxygen longer and who were older when completely nipple fed (p < .01). PMID- 8478737 TI - Obstetric infection control in a developing country. AB - In Ghana, infection has been identified as a major cause of birth-related mortality. Results of a 2-month observation of infection control practices among Ghanaian obstetric nurses and midwives indicated that most personnel did not practice basic rules of asepsis. Problems included frequent breaks in technique, inadequate sterilization and disinfection, and repeated exposure to large amounts of blood and vaginal secretions. Supplies were limited and, even when available, not always used appropriately. The situation in developing countries is different from that in the United States. Therefore, an observational needs assessment is essential to plan relevant and practical measures for change. PMID- 8478739 TI - Changes in attitudes toward cesarean birth. AB - OBJECTIVE: To compare the findings of three studies of women's responses to planned and unplanned cesarean birth. DESIGN: Descriptive. SETTING: Private obstetric practices, childbirth education classes, and hospital postpartum units. PARTICIPANTS: Study 1: 24 women who had cesarean deliveries between 1973 and 1980; Study 2: 15 women who delivered in 1981-82; Study 3: 173 women who delivered in 1989-90. MAIN OUTCOME MEASURE: Qualitative data were obtained by an investigator-developed open-ended questionnaire that was mailed to participants after cesarean delivery. RESULTS: The findings from the three studies indicate that the dominant responses to cesarean birth are happiness and excitement about the newborn, accompanied by disappointment about having to have a cesarean delivery. The women in Study 1 expressed the highest proportion of ineffective responses and the lowest proportion of adaptive responses (p = .003), whereas the women in Studies 2 and 3 expressed approximately equal percentages of adaptive and ineffective responses. Women who had unplanned cesarean deliveries had a lower percentage of adaptive responses and a higher percentage of ineffective responses than those who had planned cesarean deliveries (p < .05). Women who had regional anesthesia had more adaptive responses than those who had general anesthesia (p = .0217). CONCLUSION: The findings suggest that women who deliver by cesarean section require continued attention and sensitive care that takes into account their special needs for information, for the presence of their partners throughout the birth experience, and for sustained contact with their newborn. PMID- 8478741 TI - Propagation of photon-density waves in strongly scattering media containing an absorbing semi-infinite plane bounded by a straight edge. AB - Light propagation in strongly scattering media can be described by the diffusion approximation to the Boltzmann transport equation. We have derived analytical expressions based on the diffusion approximation that describe the photon density in a uniform, infinite, strongly scattering medium that contains a sinusoidally intensity-modulated point source of light. These expressions predict that the photon density will propagate outward from the light source as a spherical wave of constant phase velocity with an amplitude that attenuates with distance r from the source as exp(-alpha r)/r. The properties of the photon-density wave are given in terms of the spectral properties of the scattering medium. We have used the Green's function obtained from the diffusion approximation to the Boltzmann transport equation with a sinusoidally modulated point source to derive analytic expressions describing the diffraction and the reflection of photon-density waves from an absorbing and/or reflecting semi-infinite plane bounded by a straight edge immersed in a strongly scattering medium. The analytic expressions given are in agreement with the results of frequency-domain experiments performed in skim milk media and with Monte Carlo simulations. These studies provide a basis for the understanding of photon diffusion in strongly scattering media in the presence of absorbing and reflecting objects and allow for a determination of the conditions for obtaining maximum resolution and penetration for applications to optical tomography. PMID- 8478740 TI - Pelvic inflammatory disease: risk factors and microbial etiologies. AB - OBJECTIVE: To review the risk factors and microbial etiologies of pelvic inflammatory disease (PID). DATA SOURCES: Include 77 current and historical references on PID, PID risk factors, and sexually transmitted diseases. STUDY SELECTION: 34 studies that address specific research questions. DATA EXTRACTION: Data were used from studies whose methodologies are discussed. DATA SYNTHESIS: This review identifies research problems regarding the definition, diagnosis, and identification of microbial profiles and risk factors of PID. CONCLUSIONS: More reliable diagnostic criteria for the varied clinical presentations of this polymicrobial infection are needed. PID is a disease with multiple, interrelated risks. Education is an important nursing intervention. PMID- 8478742 TI - Ideal observer for discrimination of the global direction of dynamic random-dot stimuli. AB - Random-dot cinematograms in which each dot's successive movements are randomly drawn from a Gaussian distribution of directions can produce a percept of global coherent motion in a single direction. Discrimination of global direction was measured for various exposure durations, stimulus areas, and dot densities and bandwidths of the distribution of directions. Increasing the duration produced a greater improvement in performance than did increasing either the area or the density. Performance decreased as the distribution bandwidth increased. An ideal observer model was developed, and the absolute efficiency for human direction discrimination was evaluated. Efficiencies were highest at large distribution bandwidths, with average efficiencies reaching 35%. A local-global noise model of direction discrimination, based on the ideal-observer model, containing a spatial and temporal integration limit as well as internal noise, was found to fit the human data well. The utility of ideal-observer analyses for psychophysical tasks and the interpretation of efficiencies is discussed. PMID- 8478743 TI - Measurements of chromatic and achromatic afterimages. AB - Several types of measurement were made of the negative afterimages formed by viewing chromatic and achromatic sine-wave conditioning gratings that were stabilized on the retina. We varied the spatial frequency, contrast, and duration of the conditioning stimulus and the interval between its offset and the afterimage measurement. Different methods of measuring afterimage contrast were also compared. We conclude that (1) an isoluminant chromatic stimulus creates an isoluminant chromatic afterimage; (2) afterimage contrast is linearly related to conditioning contrast; (3) chromatic and achromatic afterimages have similar low pass spatial-frequency characteristics; (4) both types of afterimage build up and decay exponentially, with a (1/e) time constant of 4-8 s; (5) most important, both chromatic and achromatic afterimages raise the threshold for a chromatic flashed grating, but neither affects the threshold for an achromatic flashed grating; (6) we can explain these results by postulating that negative afterimages are subserved only by the sustained, or parvocellular, pathways. PMID- 8478744 TI - Detection mechanisms in L-, M-, and S-cone contrast space. AB - Detection thresholds were obtained for a 2 degrees Gaussian-blurred spot flashed for 200 ms on an 8.9 degrees white adapting field of 1070 trolands. The spot's contrast was represented in an L-, M-, and S-cone contrast space. Detection thresholds were obtained for many vectors close to specific but theoretically important planes within this space. A three-dimensional surface was fitted to the data generated by the probability summation of three mechanisms, each a weighted sum of cone contrasts. The fit revealed a red-green chromatic mechanism driven by delta L/L--delta M/M with no S-cone input that was 1 order of magnitude more sensitive than the two other mechanisms. The latter consisted of a luminance mechanism with little S-cone input and a blue-yellow chromatic mechanism with the S cone opposed to L and M cones. PMID- 8478745 TI - Mapping cone photopigment optical density. AB - The distribution of cone photopigment across the retina affects the amount of light captured by cones at each retinal location. Cone photopigment optical density is measured in two ways, with reflectometry and/or with color matching. Color matching measures a higher optical density than does reflectometry. Control experiments confirm that large-field color matches measure photopigment optical density toward their outer edge. There is qualitative agreement as to photopigment distribution from both techniques near the fovea. Beyond 1 deg, color matching indicates little decrease in photopigment with increasing eccentricity, whereas retinal densitometry shows a steep decline in photopigment. The decrease in perifoveal optical density measured with reflectometry is attributed to the decrease in cone coverage from fovea to perifovea as rods and interphotoreceptor spaces increase. Differences among subjects in photopigment distribution near the fovea, measured with both techniques, reflect differences in the specialization of the foveal center for cone length and/or photopigment concentration per cone, which are factors influencing results from both techniques. PMID- 8478746 TI - Modulation transfer of the human eye as a function of retinal eccentricity. AB - We measured the monochromatic image quality of the eye across a wide visual field (120 degrees), with natural pupil (4 mm) and accommodation (3 diopters). The method is based on the acquisition and the posterior processing of double-pass aerial images of a point source imaged on the retina, which was kept at a fixed distance from the eye at all retinal eccentricities. The two-dimensional modulation transfer functions (MTF's) computed from the aerial images show that astigmatism is the dominant monochromatic aberration in both the fovea and the periphery and is also the major cause of variability among individuals. We found a slower decline in optical quality with eccentricity than had been found by previous measurements. Our foveal results are in close agreement with those of Campbell and Gubisch [J. Physiol. (London) 186, 558-578 (1966)], but off-axis optical quality is much better than found previously by Jennings and Charman [Am. J. Optom. Physiol. Opt. 55, 582-590 (1978); Vision Res. 21, 445-454 (1981)]. The optical system of the eye seems to follow a wide-angle lens design: the optical quality in the center (fovea) is not particularly good (it is far from the diffraction limit at this pupil size), but the modulation transfer function remains roughly constant for a wide visual field. PMID- 8478747 TI - Experimental determination of the chromatic difference of magnification of the human eye and the location of the anterior nodal point. AB - Theory predicts that retinal image size will vary with wavelength. However, this chromatic difference of magnification (CDM) is likely to be very small (< 1% between 400 and 700 nm) under natural viewing conditions. There has been only one attempt to measure CDM experimentally, and the results were inconsistent with optical theory. Using a technique described by Ogle [Research in Binocular Vision, Hafner, New York (1964)], which is sensitive to even small interocular differences in retinal image size, we measured the apparent tilts in the frontoparallel plane induced by interocular differences in wavelength. We obtained the ocular CDM by determining the afocal lens magnification necessary to cancel the apparent frontoparallel plane tilt caused by interocular differences in wavelength. We show that (1) the ocular CDM can be considerably less than theoretical model predictions, (2) the relationship among delta Rx (wavelength dependent refractive error), CDM, and pupil position is consistent with our theoretical model, (3) CDM increases considerably when an artificial pupil in front of the eye is used, (4) the location of the anterior nodal point of the eye may be inferred from the data, and (5) unlike in the case for delta Rx, large intersubjective differences may exist for CDM. The results suggest caution in the use of artificial pupils experimentally with polychromatic stimuli because of amplification of CDM and concomitant losses of image contrast. PMID- 8478749 TI - Theory of wavelength discrimination in tritanopia. AB - Many theories of color discrimination predict a discontinuity in the wavelength discrimination function of a tritanope at the point in the spectrum at which the rate of change of the visual signal constrained to an equiluminant plane passes through zero (near 460 nm). The predicted discontinuity follows from the use of a first-order approximation for which the reciprocal of the slope of the response function that generates the visual signal is proportional to the discrimination limen. In view of the good discrimination shown by such observers elsewhere in the spectrum, however, such a singularity is impossible. I show that the inclusion of the higher-order terms produces a finite value in the 460-nm region that falls in the range of values from the literature that have been obtained experimentally. PMID- 8478748 TI - Color matching at high illuminances: photopigment optical density and pupil entry. AB - Changes in the effective optical density of the cones are sufficient to explain changes in color matches with retinal illuminance and pupil entry. We performed three experiments. In the first experiment, six observers made color matches under both bleached and unbleached conditions to a series of six standard wavelengths. The effects of bleaching could be modeled by a decrease in optical density of the L and M cone photopigments. Slight spectral shifts in the peak wavelengths of the photopigments were required for different observers. In the second experiment we varied retinal illuminance of the color-matching field from 2.4 to 5.4 log Td for a series of long-wavelength primaries. The shape of the color match versus the intensity function was unchanged by the wavelength composition of the matching field. In the third experiment we measured the change in color match with retinal illuminance for different pupil entry positions. At low luminances there was a marked dependence of the color match on pupil entry positions. At high illuminance there was only a small dependence. The half-bleach illuminance values varied as expected from the Stiles-Crawford I effect. We conclude that for wavelengths > 540 nm, changes in color matches with bleaching and pupil entry can be explained by changes in the effective optical density of the cones. PMID- 8478750 TI - Treatment of a severe drug-induced gingival hyperplasia on a medically compromised patient--a case report. PMID- 8478751 TI - Dental hypersensitivity: recent advances in diagnosis and treatment. AB - Dentinal hypersensitivity affects eating, brushing, drinking, and breathing habits. Each dentist must know its manifestations and management. Hypersensitive teeth are not temporary annoyances. Dental patients want and expect solutions to the hypersensitivity problem. The latest diagnostic and treatment skills, along with new products and reimbursement procedures, can be offered as part of your practice-building agenda. PMID- 8478753 TI - Nutrition education for the oral and maxillofacial surgeon. PMID- 8478752 TI - Hospital dental program serves severely apprehensive and medically-compromised patients. PMID- 8478754 TI - Mandibular reconstruction. PMID- 8478755 TI - Ophthalmic complications associated with orthognathic surgery. AB - Ophthalmic complications are rare following maxillary osteotomies. Potential complications include a decrease in visual acuity, extraocular muscle dysfunction, neuroparalytic keratitis, and nasolacrimal problems involving both an increase or a decrease in tearing. Ophthalmic injuries appear to be primarily mediated through indirect injuries to neurovascular structures occurring from traction, compression, or contrecoup injuries from forces transmitted during the pterygomaxillary dysjunction using an osteotome or from fractures extending to the base of the skull or orbit associated with the pterygomaxillary dysjunction or the maxillary downfracture. A review of the literature of previous ophthalmic complications as well as eight new cases are reported. The possible etiologic basis for these injuries is discussed in detail as well as treatment possibilities when appropriate. PMID- 8478756 TI - The role of physical therapy in recovery after temporomandibular joint surgery. AB - The purpose of this study was to investigate the effect of aggressive physical therapy on the rehabilitation of patients who have had temporomandibular joint (TMJ) surgery. The control group consisted of 26 postsurgical patients who had no physical therapy, and the treatment group consisted of 24 postsurgical patients who were treated with aggressive therapy for 8 weeks. Patients in both groups had range of motion measurements taken at 1 and 8 weeks. The ratio of patients in the treatment group who achieved normal range of motion was compared with the ratio of patients in the control group who achieved it. The results showed a significantly greater range of opening in experimental than in control subjects at 8 weeks but not for lateral excursions. These results suggest that aggressive physical therapy is an important adjunct to postsurgical care for patients with TMJ. PMID- 8478757 TI - Effects of extensive oral surgery and hemorrhage on coagulation and fibrinolysis. AB - The changes in coagulation and fibrinolytic activity in 22 patients with oral cancer undergoing extensive surgical procedures were studied. The patients were divided into two groups: group I patients suffered blood loss of less than 2,000 mL and group II patients had blood loss of more than 2,000 mL. The platelet count decreased significantly during surgery, at the end of surgery and on the 1st postoperative day in both groups. Fibrinogen was decreased during and at the end of surgery in both groups, but increased significantly on the 3rd postoperative day and reached about two times the preoperative levels on the 7th postoperative day. Fibrin degradation products increased significantly after surgery and reached the maximum value on the 1st postoperative day in both groups. Plasmin inhibitor complex and plasminogen increased significantly on the 3rd and 7th postoperative days. There was no clear evidence regarding the influence of blood loss on coagulation and fibrinolytic factors except for platelets. It was concluded that coagulation and fibrinolysis are enhanced between the 3rd and 7th postoperative days. PMID- 8478758 TI - Nasal tip modification using four distinct methods. AB - Oral and maxillofacial surgeons are combining orthognathic surgery with rhinoplasty. In many instances, alteration of the tip is the key to attaining an esthetically pleasing nasal shape. This article addresses four separate procedures for tip modification. Tip support and a variety of surgical nuances, highlighting the open technique, are discussed. PMID- 8478759 TI - Comparison of rectal midazolam and diazepam for premedication in pediatric dental patients. AB - Rectally administered midazolam (0.35 mg/kg) and diazepam (0.70 mg/kg) were compared with each other and with placebo for preanesthetic medication in children undergoing dental extractions. All rectal medications were very well accepted, but mask acceptance, improvement in anxiety, and sedation were best in the midazolam group. Improvement in anxiety and sedation were significantly better in the two drug groups than in those patients who had received placebo. Thirty minutes after rectal administration of midazolam, patients showed a decrease in both systolic and diastolic blood pressure and heart rate. Although these decreases differed significantly from the premedication values, they were probably of little clinical importance. Only minor adverse effects were observed in this study. Overall rectally administered midazolam appeared to be somewhat more efficacious than diazepam. PMID- 8478760 TI - Long-term viability of the temporalis muscle/fascia flap used for temporomandibular joint reconstruction. AB - Temporalis muscle/fascia axial flaps (TFs) were used in 115 temporomandibular joints (TMJs) in 81 patients to correct ankylosis (n = 25 joints), traumatic defects (n = 8), congenital anomalies (n = 4), defects resulting from tumor resection (n = 2), degenerative joint disease (n = 52), autoimmune arthritides (n = 21), and lateral capsule flaccidity (n = 3). The follow-up period ranged from 6 months to 5.5 years. Seven patients (8.6% of the group; 10 TMJs) were reevaluated for recurrent symptoms (pain and decreased motion), with a mean of 1.7 years (range = 1 to 3 years) postoperatively. Four of these patients (seven TMJs) had magnetic resonance imaging (MRI) as part of their diagnostic workup and four patients (five TMJs) required a second operative procedure. This study reports the results of the MRI, intraoperative, and histologic evaluations of the TFs in these seven patients. The MRIs showed vascularized tissue between the condyle and roof of the glenoid fossa in all seven joints examined. The signal was consistent with muscle and/or fat as opposed to scar tissue. All flaps examined at the time of surgery (arthroscopy, n = 1; arthrotomy, n = 4) were in place and had the gross appearance of normal muscle. Histologic examination of biopsies of four flaps indicated the presence of viable muscle with normal-appearing nuclei. The results of this study indicate that the TF does survive when it is carefully dissected and inferiorly based to preserve blood supply. PMID- 8478761 TI - Principles of management of complex craniofacial trauma. AB - Successful treatment of patients with complex craniofacial injuries is heavily dependent on the surgeon's appreciation of the associated nonfacial injuries, precise clinical and diagnostic imaging examinations to establish a three dimensional configuration of the fractured segments, and the application of well established principles of facial fracture repair. Factors that influence improved treatment outcome are 1) early definitive treatment, 2) anatomic and functional repair of naso-orbito-ethmoidal injuries, 3) wide exposure of fracture segments, and 4) anatomic repositioning and stable fixation of fracture segments in all planes of space. PMID- 8478762 TI - Sequencing treatment for naso-orbito-ethmoid fractures. AB - This article presents a strategy for treating naso-orbito-ethmoid fractures. Eight steps for the management of such injuries are presented: surgical exposure, identification of the medial canthal tendon/tendon-bearing bone fragment, reduction/reconstruction of medial orbital rim, reconstruction of the medial orbital wall, transnasal canthopexy, reduction of septal fractures, nasal dorsum reconstruction/augmentation, and soft tissue adaptation. Following these steps can make treatment outcomes more predictable. PMID- 8478763 TI - Expanding the specialty: a survey of oral and maxillofacial surgery residencies in the United States. AB - This article reports the results of a survey of oral and maxillofacial surgery (OMS) residency program directors regarding teaching of expanded scope surgical procedures during the academic year 1990 to 1991. Data is provided for the nation as a whole, as well as grouped by geographic regions and type of residency program. Significant differences were found for some procedures based on both geographic region and program type. The majority of program directors responding to this survey disagreed with the trend toward expanding the scope of OMS into cosmetic procedures. Directors of integrated dual degree programs believed that the trend toward expanding the scope of OMS was positive; 2:1 over directors of MD optional or traditional OMS programs. PMID- 8478764 TI - Paresthesia of the mandibular division, trigeminal nerve. PMID- 8478765 TI - Parotid gland metastases from orbital tumors: report of two cases. PMID- 8478766 TI - The role of labial salivary gland biopsy in the diagnosis of Sjogren's syndrome: report of three cases. PMID- 8478767 TI - Necrosis of the lip in giant cell arteritis: report of a case. PMID- 8478768 TI - Adult T-cell leukemia with initial presentation as sinonasal lymphoma: report of two cases. PMID- 8478769 TI - Thyroid metastasis to the oral soft tissues: case report of a diagnostic dilemma. PMID- 8478770 TI - Management of an ingested iatrogenic foreign body: report of a case. PMID- 8478771 TI - Recurrent oral bleeding in Maffucci's syndrome: report of a case. PMID- 8478772 TI - Primary meningioma of the infratemporal fossa: a clinicopathologic and immunohistochemical study. PMID- 8478773 TI - Angioneurotic edema mimicking Ludwig's angina: a case report. PMID- 8478774 TI - Titanium screw failure: a case report. PMID- 8478775 TI - Split-thickness skin graft harvesting from an intraoral flap: a new technique. PMID- 8478776 TI - The proper orientation of oral and maxillofacial surgery training. PMID- 8478777 TI - A swat at the SWOT. PMID- 8478778 TI - A retrospective look at tip location and complications of peripherally inserted central catheter lines. AB - In 1982, Southern Regional Medical Center in Riverdale, Ga, instituted a program for selected intravenous nurses to insert and manage peripherally inserted central catheters (PICCs). At present, approximately 125 to 150 PICCs are inserted annually by eight experienced IV nurses. In this retrospective study, the authors review medical record data on PICC insertions that occurred between January 1987 and December 1991. The optimal tip location is defined as the superior vena cava (SVC) and an anterior-posterior one-view chest x-ray is performed to confirm tip location. This study focuses on the initial location of the PICC and actions taken to correct the initial tip placement if not in the SVC. Medical records were reviewed for complications including mechanical phlebitis, infections, ruptured catheters, clotted catheters, or vein thromboses. The frequency of these complications, their prevention, and management are discussed. PMID- 8478779 TI - How to evaluate study methodology in published clinical research. AB - When reading a clinical research article, the clinician must judge if the reported findings and conclusions are valid before applying them to patient care. This concern is legitimate given the wide range of study validity in the clinical literature. In this article, the authors present many validity markers that signify the quality of the information reported from a study, such as authorship, bias, confounding, statistics, randomization, controls, blinding, and the logical framework of scientific investigations. PMID- 8478780 TI - "Allergic-type reaction" to a Landmark catheter. PMID- 8478781 TI - Re: "Implantable ports" by Dawn Camp-Sorrell. PMID- 8478782 TI - An overview of ondansetron for chemotherapy-induced nausea and emesis. AB - Nausea and vomiting are major complications associated with the administration of cytotoxic drugs. Ondansetron (Zofran, Glaxo, Inc., Research Triangle Park, NC), a 5-hydroxy tryptamine (5-HT3) serotonin antagonist, has shown efficacy in managing chemotherapy-induced nausea and vomiting without extrapyramidal side effects. The author provides an overview of recent studies and manufacturer's administration recommendations, as well as guidelines for nursing care and patient teaching. PMID- 8478783 TI - The peripherally inserted central catheter: a retrospective look at three years of insertions. AB - The advent of intravenous therapies administered in the home setting has created a demand for the peripherally inserted central catheter (PICC). A variety of PICCs is now on the market, offering choices of insertion methods as well as size and length. This article represents a retrospective look at 858 PICCs inserted over a 3-year period, using three insertion methods: 1) the Seldinger technique, 2) the peel-away sheath, and 3) the break-away needle. A brief history of PICCs along with problems encountered, an account of PICCs in immune-suppressed patients, and principles of catheter management are presented. PMID- 8478784 TI - Epithelial cell-fibroblast interactions: modulation of extracellular matrix proteins in cultured oral cells. AB - A model system involving co-cultures of human gingival or periodontal ligament fibroblasts with mouse epithelial root sheath cells or human gingival epithelial cells was used to study epithelial cell-fibroblast interactions. Double-labeled immunofluorescence and microfluorometry were used to investigate the expression of extracellular matrix molecules of collagen type I (collagen I), type III (collagen III) and fibronectin in fibroblasts. When fibroblasts from either source were cultured alone, the fluorescence for collagen I and fibronectin ranged from strongly positive to almost negative. Collagen III staining was relatively weak compared with that of collagen I. After 2-3 days of co-culture, gingival fibroblasts and ligament fibroblasts adjacent to the mouse sheath cells exhibited enhanced intracellular fluorescence for collagen I and fibronectin. Very little change was observed for collagen III. Gingival fibroblasts cultured with gingival epithelial cells showed increased fluorescence for collagen I but decreased fluorescence for fibronectin. In contrast, the fluorescence intensity for both collagen I and fibronectin in ligament fibroblasts were reduced after 3 days of co-culture with gingival epithelial cells. Ultrastructural changes in fibroblasts co-cultured with mouse root sheath cells included increased Golgi cisternae and vesicles and an increased abundance of rough endoplasmic reticulum, polyribosomes, secretory vesicles and pinocytotic vesicles. Thus, the expression of extracellular matrix proteins and the metabolic activity of fibroblasts can be modulated by oral epithelial cells. PMID- 8478785 TI - Concentrations of thiocyanate, hypothiocyanite, 'free' and 'total' lysozyme, lactoferrin and secretory IgA in resting and stimulated whole saliva of children aged 12-14 years and the relationship with plaque accumulation and gingivitis. AB - Resting and stimulated whole saliva was collected from 94 children aged 12-14 years and analyzed for thiocyanate, hypothiocyanite, 'free' and 'total' lysozyme, lactoferrin and secretory IgA. Clinical assessments of the amounts of plaque and gingival inflammation were made, and plaque was collected for determination of dry weight. An inverse relationship was observed between salivary thiocyanate concentrations in both resting and stimulated saliva and the amounts of plaque and gingival inflammation in these subjects (p < 0.05). Lactoferrin concentration in stimulated saliva was directly related to the amounts of plaque and gingivitis (p < 0.05). 'Total' lysozyme concentration in stimulated saliva was directly related to the amount of plaque (p < 0.05), and the 'free' lysozyme concentration in the same saliva was directly related to the amount of gingivitis (p < 0.05). The direct relationship observed between clinical measurements and both lysozyme and lactoferrin concentrations in saliva may have been due to contributions from gingival crevicular fluid. Cluster analysis identified three groups of subjects with different profiles in resting whole saliva, and in particular with different levels of secretory IgA. A statistically significant difference was observed in the quantity of plaque collected from subjects in two of these groups (p < 0.05). These results from cluster analysis using resting whole saliva from children confirmed the findings of a previous study with young adults. PMID- 8478786 TI - Kinetics of CD11b expression on neutrophils isolated from subjects with healthy gingivae and patients with advanced periodontitis. AB - The adhesion molecule, CD11b/CD18, plays a role in host defense against bacterial infections owing to its involvement in cell migration and phagocytosis. We examined the kinetics of CD11b expression on neutrophils isolated from peripheral blood (PB-PMNs) and gingival crevicular fluid (CF-PMNs) in subjects with healthy gingivae and in patients with advanced periodontitis in order to assess if CF PMNs respond differently in regard to CD11b expression from PB-PMNs isolated from healthy or periodontitis subjects. CF-PMNs or formylmethionylleucylphenylalanine (fMLP)-stimulated PB-PMNs were incubated in buffer with or without divalent cations for 60, 90, or 110 minutes. Plasma membrane (surface) CD11b as measured by flow cytometry was found to be reduced with time when cells (PB-PMNs or CF PMNs) from either controls or patients were treated with calcium- and magnesium free buffer. However, when CF-PMNs were treated with buffer containing Ca++/Mg++, surface CD11b expression increased on cells from both controls and patients. The reduction in CD11b expression on PB-PMNs is significantly greater than that measured on CF-PMNs over time. Therefore, CF-PMNs respond differently from PB PMNs which have been artificially stimulated with fMLP in regard to kinetics of CD11b expression on the plasma membrane. PMID- 8478787 TI - Change detection on longitudinal data in periodontal research. AB - Longitudinal data of attachment level (AL) or the alveolar bone level are often used to assess the progression of periodontal disease. This paper tries to identify the most efficient method to detect the changes of AL in a general periodontal research environment; that is, a sequential decision based on multiple sites. Several existing methods suggested in the periodontal research literature such as the tolerance, running median, cusum, and regression methods as well as change-point detection methods in the statistical literature are examined. It is found that the regression method is most convenient among the several methods that are equally effective in change detection. Formulae, tables and their usage are discussed in detail. PMID- 8478788 TI - Partial characterization of proteoglycans synthesized by human gingival epithelial cells in culture. AB - Proteoglycans (PGs) were extracted from the [35S]-sulfate labelled medium and cell layer of proliferating human gingival epithelial cells and analyzed by ion exchange and molecular sieve chromatography, and by SDS-PAGE. The majority of the incorporated radioactivity secreted into the medium eluted from a DEAE Sephacel ion exchange column as a single peak at 0.44 M NaCl with a small shoulder at 0.52 M NaCl. This material, when chromatographed on Sepharose CL-6B contained two species--a quantitatively major peak at K(av) = 0.30 (M(r) congruent to 235,000 on SDS-PAGE) and a quantitatively minor peak at K(av) = 0.39. The major peak was sensitive to alkaline borohydride, shifting to K(av) = 0.45, and nitrous acid degradation, indicating the presence of heparan sulfate PG with glycosaminoglycan chains with M(r) congruent to 26,000. The minor peak is chondroitin/dermatan sulfate PG with glycosaminoglycan chains of M(r) = 22,200 as indicated by sensitivity to alkaline borohydride (shifting to K(av) = 0.48) and chondroitin ABC lyase digestion. The [35S]-sulfate labelled material from the cell layer eluted in a broad peak between 0-0.50 M NaCl from DEAE Sephacel. Chromatography of this material on Sepharose CL-6B revealed the presence of three peaks at K(av) = 0.20, 0.31, and 0.75. The largest peak (K(av) = 0.20 and M(r) congruent to 245,000 on SDS-PAGE) shifted elution position to K(av) = 0.50 after alkaline borohydride treatment and was completely sensitive to nitrous acid degradation. These results indicate that this peak contains heparan sulfate PG with glycosaminoglycan chains of M(r) congruent to 20,000. Two peaks containing [35S] sulfate labelled glycosaminoglycan chains were detected by chromatography of the cell layer extract over Sepharose CL-6B with K(av)S = 0.42 (M(r) congruent to 30,500) and 0.75 (M(r) congruent to 5300). The larger peak was predominantly chondroitin/dermatan glycosaminoglycan as indicated by susceptibility to chondroitin ABC lyase while the chains at K(av) = 0.75 were predominantly heparan sulfate with 83% susceptibility to nitrous acid. These results indicate that cultured human gingival epithelial cells synthesize and secrete principally heparan sulfate PGs with small amounts of chondroitin/dermatan sulfate PGs. This work will serve as a basis for future studies designed to examine those factors involved in regulation of PG synthesis by these cells. PMID- 8478789 TI - Interactions of chlorhexidine with salivary films adsorbed at solid/liquid and air/liquid interfaces. AB - Chlorhexidine is a cationic compound which has been shown to bind to salivary proteins and enamel through electrostatic interactions. The aims of this study were to investigate the interaction of chlorhexidine molecules with salivary films adsorbed on solid surfaces with varying physico-chemical characteristics and to investigate the effect of different concentrations of chlorhexidine on the surface tension of saliva. The interactions between 0.2% chlorhexidine digluconate with films adsorbed from whole saliva were monitored by a Rudolph Thin-film ellipsometer equipped with a He-Ne laser (632.8 nm). The films were adsorbed on hydrophilic silica surfaces which were plasma cleaned or on methylated hydrophobic surfaces. Experiments of chlorhexidine adsorption on bare surfaces were also performed. The surface tension of mixtures of whole saliva with various concentrations of (0.1%, 0.2%, 1%) chlorhexidine was monitored with a tensiometer. The results show that chlorhexidine adsorbs on both types of studied substrates. Addition of the substance followed by rinsing caused a partial desorption of the adsorbed pellicles. Furthermore, at all studied concentrations chlorhexidine reduced the interfacial tension. There are indications that the amphiphilic characteristics of the molecule play an important role in the retention of the substance in the oral cavity. PMID- 8478790 TI - Microbial degradation of aquatic biomass by Trichoderma viride 992 and Aspergillus wentii 669 with reference to the physical structure. AB - There was a considerable change in the structural parameters of both the lignocellulosic substrates. This change was confirmed by infrared (IR) spectroscopy and X-ray diffraction data, which revealed the presence of phenolic groups in the peaks range 1310-1410 and 1200 cm-1 with large crystalline substrates. These were found to be reduced after treatment with alkali. Enzyme/s activity were found to be increased after pretreatment of hydrolysed substrates. The structural modifications in both the substrates were further evidenced by the results obtained after enzymatic hydrolysis of alkali-treated substrates. PMID- 8478791 TI - The effect of light and glucose concentration on the content of S- and R-glucans in the mycelium of Aspergillus giganteus mut. alba. AB - The amounts of S- and R-glucans in the mycelium of Aspergillus giganteus mut. alba depend on light within the range of selected light intensities: 0 W.m-2; 3 W.m-2; 10.6 W.m-2 at 20% glucose concentration in the nutrient medium. This species synthesizes the highest amount of S-glucans at the light intensity 10.6 W.m-2, and that of R-glucans--at the intensity 3 W.m-2. PMID- 8478792 TI - A genetic study of apramycin-resistant mutants of Escherichia coli. AB - The apramycin-resistant mutants of E. coli were isolated spontaneously. Mutations, aprA and aprB, conferring resistance to apramycin were located at 72 min on the E. coli genetic map where most of ribosomal genes were mapped. One of the mutants, carrying the aprB mutation, has an altered translational fidelity expressed as severe restriction of amber suppressor activity in vivo. The chromosome location and altered translational fidelity indicate that the apramycin-resistant phenotype could be a consequence of an alteration of the ribosomal structure. PMID- 8478793 TI - Steroid metabolism with intestinal microorganisms. AB - As a result of the metabolic activities of numerous anaerobic microorganisms with sterols, bile acids and steroid hormones as substrates in connection with the enterohepatic circulation of these compounds, the intestine may be considered as an "endocrine" active site or organ. The review summarizes transformations of steroids by anaerobic intestinal bacteria, the physiological and supposed pathophysiological meaning thereof. The aim is to recommend further investigation in this field with respect to both the elucidation of the reactions and biological responses. PMID- 8478794 TI - Panmetatarsal head resection. A viable alternative to the transmetatarsal amputation. AB - While the transmetatarsal amputation has resulted in the salvage of numerous diabetic limbs, it remains an ablative procedure with both short- and long-term complications. The authors reviewed their experience with the panmetatarsal head resection as an alternative to the transmetatarsal amputation. A retrospective review was performed of all patients having undergone this procedure between May 1986 and November 1991. Thirty-seven procedures were performed; of these, 34 were evaluated. The average follow-up period was 20.9 months. Thirty-two feet showed primary healing while one showed delayed healing. One patient had local recurrence of the original ulceration. Primary healing was 94% while overall success was 97%. No patient required amputation of any kind. The authors conclude that the panmetatarsal head resection is a viable alternative to the transmetatarsal amputation in properly selected patients because it avoids many of the structural and biomechanical pitfalls of the transmetatarsal amputation. PMID- 8478795 TI - Postgraduate podiatric medical education. PMID- 8478796 TI - Morton's neuroma. PMID- 8478797 TI - Transmetatarsal amputation for infection or gangrene in patients with diabetes mellitus. 1949. PMID- 8478798 TI - A historical look at the transmetatarsal amputation and its changing indications. AB - In March 1949, McKittrick described the use of the transmetatarsal amputation for the diabetic foot, along with specific indications. Infection, ischemia, and neuropathic ulcerations of the toes and forefoot were all treated with this procedure. In the past 30 years, however, advances in the management of these problems have led to a decrease in the number of transmetatarsal amputations performed at the New England Deaconess Hospital. With these advances, the current approach to the transmetatarsal amputation has changed, leading to significant modifications in the basic indications for this procedure. PMID- 8478799 TI - A biomechanical model for the transmetatarsal amputation. AB - The transmetatarsal amputation has been performed for over 40 years as a limb salvage procedure, in diabetic patients with nonhealing ulcerations or nonreconstructible ischemia. It is generally believed that the transmetatarsal amputation provides a better walking extremity than a more proximal amputation and is more energy efficient. A review of the literature reveals little regarding the biomechanics of the "short foot." The authors will review the functions of the myofascial structures in both the normal foot and the transmetatarsal amputation and discuss the influence of mechanics on transmetatarsal amputation lesions. PMID- 8478800 TI - Salvaging the ischemic transmetatarsal amputation through distal arterial reconstruction. AB - From 1982 to 1991, 17 patients underwent a lower extremity arterial bypass to salvage an ischemic transmetatarsal amputation at the New England Deaconess Hospital. Eleven patients were male, and 16 had diabetes for an average of 29 years. The mean age was 71 years. Twelve patients presented with an ischemic ulcer, one had rest pain, and four underwent bypass for failure to heal a transmetatarsal amputation. Twelve patients presented with findings of secondary infection. All 17 patients underwent successful lower extremity bypass procedures to a variety of outflow vessels. Thirteen bypasses were to infrapopliteal arteries, including four to the dorsalis pedis artery. There were no perioperative deaths and all patients were discharged with patent grafts and healing limbs. Actuarial graft patency of the 14 vein grafts was 90% at 2 years. Actuarial limb salvage for the entire group was 93% at 2 years. Thirteen of the 14 patients who maintained patent grafts and healed their transmetatarsal amputations were ambulatory at their last known follow-up examination. Ischemic complications of previously created transmetatarsal amputations are uncommon. However, limb salvage attempts by lower extremity arterial bypass have a high likelihood of success. Major amputation in these patients should not be done without having first undergone a comprehensive vascular evaluation. PMID- 8478801 TI - Surgical revision of the problematic transmetatarsal amputation. AB - Recurrent ulcerations may develop following transmetatarsal amputation in patients with diabetes mellitus. In many cases, these ulcerations require surgical intervention to achieve healing, especially in situations where conservative care has not been effective. These procedures range from the local resection of bone to skin grafting and flap techniques to successfully heal the wound. The ultimate goal of any surgical intervention is to prevent a more proximal amputation. PMID- 8478802 TI - Tendo Achillis procedures for chronic ulcerations in diabetic patients with transmetatarsal amputations. AB - Recurrent ulceration following transmetatarsal amputation commonly results from hypertrophic bone formation or equinus deformity. In the current study, 31 diabetic patients underwent 33 Achilles tendon procedures for recurrent ulcerations at the distal stump of their transmetatarsal amputation. Primary healing was achieved in 21 procedures (64%) and secondary healing in 9 procedures (27%) for an overall healing rate of 91%. Two procedures failed to resolve the original ulceration (6%). The average follow-up examination was 27 months. The authors conclude that Achilles tendon procedures are an effective means of managing ulcerations in transmetatarsal amputation feet exhibiting an equinus deformity. PMID- 8478803 TI - Standard of care: legal implications in the postanesthesia care unit. AB - PACU staff provide specialized nursing care to diverse patient populations in an environment of constant activity, high volume, rapid turnover, and intense pressure. Nursing practice in the PACU requires quick, effective responses when emergencies occur. The PACU nurse is held to the same standard of care as any reasonably prudent nurse in similar life-threatening situations. It is essential that the PACU nurse know the standards of care, the basic elements of negligence, and the legal implications of practice. Ultimately, the responsibility for each nurse's practice lies in his or her knowledge and understanding of professional standards. These standards form the foundation of PACU nursing care. PMID- 8478804 TI - Intermediate-term intravenous therapy: a pilot study. AB - Midline catheters provide an effective alternative for intermediate-term intravenous therapy. During a pilot study, 27 midline catheters were inserted in patients who met specific criteria. The insertion success rate was 64%, and the infection rate was 7%. One mechanical phlebitis occurred, but it was resolved by the application of warm, moist heat. One chemical phlebitis occurred during antibiotic therapy. The average dwell time was 8.7 days, and the longest dwell time was 49 days. Patients reported the catheters to be very comfortable and did not experience limitations in mobility. PMID- 8478805 TI - Precious moments of caring. PMID- 8478806 TI - Infection control monitoring in the ambulatory surgery unit. AB - This article shares a plan for infection control monitoring in an ambulatory surgery unit. Simple, efficient, and effective, the plan meets the unique needs of nurses working in a high-volume unit with rapid turnover of patients where virtually no contact occurs nor is information received about patients after the first 24 hours. The success of the plan depends on the surgeons assuming responsibility for identifying and reporting their patients' postoperative infections. We have found that surgeons will respond if provided with a simple reporting system that requires minimal completion time. PMID- 8478807 TI - Patients who develop postanesthesia shaking increase body temperature at the same rate as those who do not develop shaking. AB - Postanesthesia shaking is a common complication occurring after general anesthesia. Although the cause is unknown, some nurses believe that shaking is useful and beneficial for patients because it increases body temperature and that shaking stops when patients are no longer hypothermic. The primary purpose of this study was to examine changes in body temperature among patients who developed and who did not develop shaking. Secondary purposes were to examine changes in body temperature among patients who received or who did not receive intravenous narcotic-analgesic medication treatment to stop shaking and among those who either stopped shaking or who continued to shake until spontaneous cessation occurred minutes to hours later. The convenience sample consisted of 36 shaking patients and 56 nonshaking patients who were extubated, were over 18 years of age, had an intact intravenous line, and received isoflurane anesthesia. Shaking was established when patients reached and sustained grade 2 or 3 shaking on a 0-to-3 visual scale for 3 minutes (no shaking to forceful shaking). Shaking was determined as having stopped when patients achieved grade 2 on a 0-to-2 visual scale (continues shaking to stopped shaking). Axillary temperature was measured on PACU admission and again after 60 minutes. The six hypotheses were supported. Patients who developed shaking (mean = .67 degrees C [1.2 degrees F]) changed body temperature at the same rate as those who did not develop shaking (mean = .72 degrees C [1.3 degrees F]). Administration of intravenous narcotic analgesic medication to stop shaking did not alter the rate of body temperature change in patients who received or who did not receive treatment for shaking and those who did or who did not stop shaking. Findings suggest that postanesthesia shaking does not increase body temperature. This finding does not support the long-held belief that shaking is useful and beneficial for patients because it increases body temperature. Findings also indicated that the administration of intravenous narcotic-analgesic medications to stop shaking does not alter the rate of body temperature change. Suggestions for further research focus on systematically examining nursing interventions currently implemented to stop shaking. Research findings will provide evidence that either supports or fails to support the implementation of therapeutic interventions that effectively stop shaking within 5 minutes. PMID- 8478808 TI - Practical points in the care of the patient post-cleft lip and palate repair. AB - It is the purpose of this article to discuss care of the patient post-cleft lip and palate repair. The incidence and epidemiology of clefting is presented. Surgical goals and procedures are discussed, and special attention is given to PACU priorities. PMID- 8478810 TI - The essence of leadership: facing the challenge of being the new manager. AB - To meet the challenge of today's work environment, the leader of a professional, technically skilled, and highly diverse work "group must be an enabler of people, a facilitator of groups, as well as know how to be an effective group member" (Blanchard et al, The One Minute Manager Builds High Performance Teams, New York, NY, William Morrow, 1990). To accomplish this the leader must participate as a member of the work group as well as identify areas of needed management support and direction. Creating the climate that allows professional work teams to develop and mature is both challenging and rewarding. Fully mature, high performance teams require minimal direction from the leader. At this stage empowerment is reached: the leader lets go so that the team can get going. PMID- 8478809 TI - Introduction to instrument development: scaling methods. AB - Deciding which instrument scale technique to choose is an important step in instrument development. Measurement theory dictates rules regarding level of measurement and approaches to decrease the error component of true scores. Measurement rules are applied to types of scaling, including methods to quantify demographic data, opinion rating scales, summated rating scales, semantic differential scales, and methods to quantify laboratory data. Consideration to scaling should be made before planning data analysis so that research questions or hypotheses can be answered using the appropriate statistical method. PMID- 8478811 TI - Healthy neighbors: exploring the health care systems of the United States and Canada. AB - Millions of Americans are without insurance or access to health care. The health care industry, politicians, government, concerned groups, and individuals are struggling with proposals for a system that will ensure basic care for all our citizens. The Canadian system is often suggested as a model for the United States. Allen recently visited Canada and spoke with residents in Nova Scotia and Newfoundland about their health care. Kardos has done extensive research on various systems designed to provide universal access to health care. In the following article the authors offer information, make comparisons, and pose questions for readers. PMID- 8478812 TI - Beyond blame: modeling achievement. PMID- 8478813 TI - Central auditory neurophysiology of a sound-producing fish: the mesencephalon of Pollimyrus isidori (Mormyridae). AB - This paper describes the auditory neurophysiology of the mesencephalon of P. isidori, a sound-producing mormyrid fish. Mormyrids have a specialized pressure sensitive auditory periphery, and anatomical studies indicate that acoustic information is relayed to the mesencephalic nucleus MD. Fish were stimulated with tone bursts and clicks, and responses of MD neurons were recorded extracellularly. Auditory neurons had best frequencies (BF) and best sensitivities (BS) that fell within the range of frequencies and levels of the natural communication sounds of these fish. BSs were in the range of 0 to -35 dB (re. 1.0 dyne/cm2). Many of the neurons were tuned (Q10 dB: 2-6), and had BFs in the range of 100-300 Hz where the animal's sounds have their peak energy. A range of different physiological cell types were encountered, including phasic, sustained, and complex neurons. Some of the sustained neurons showed strong phase locking to tones. Many neurons exhibited non-monotonic rate-level functions. Frequencies flanking the BF often caused a reduction in spontaneous activity suggesting inhibition. Many neurons showed excellent representation of click trains, and some showed a temporal representation of inter-click-intervals with errors less than 1 ms. PMID- 8478814 TI - Cerebral neurons underlying prey capture movements in the pteropod mollusc, Clione limacina. II. Afterdischarges. AB - The pteropod mollusc Clione limacina is a highly specialized carnivore which feeds on shelled pteropods and uses, for their capture, three pairs of oral appendages, called buccal cones. Contact with the prey induces rapid eversion of buccal cones, which then become tentacle-like and grasp the shell of the prey. In the previous paper, a large group of electrically coupled, normally silent cells (A motoneurons) has been described in the cerebral ganglia of Clione. Activation of A neurons induces opening of oral skin folds and extrusion of the buccal cones. The present study continues the analysis of the electrical properties of A motoneurons. Brief intracellular stimulation of an A neuron can produce prolonged firing (afterdischarge), lasting up to 40 s, in the entire population of A neurons. After-discharge activity is based on an afterdepolarization evoked by an initial strong burst of A neuron spikes. The data suggest that this afterdepolarization represents excitatory synaptic input from unidentified neurons which in turn receive excitatory inputs from A neurons, thus organizing positive feedback. The main functional role of this positive feedback is the spread and synchronization of spike activity among all A neurons in the population. In addition, it serves to transform a brief excitatory input to A neurons into their prolonged and stable firing, which is required during certain phases of feeding behavior in Clione. PMID- 8478815 TI - Modulation of swimming behavior in the medicinal leech. I. Effects of serotonin on the electrical properties of swim-gating cell 204. AB - The effects of serotonin on the electrical properties of swim-gating neurons (cell 204) were examined in leech (Hirudo medicinalis) nerve cords. Exposure to serotonin decreased the threshold current required to elicit swim episodes by prolonged depolarization of an individual cell 204 in isolated nerve cords. This effect was correlated with a more rapid depolarization and an increased impulse frequency of cell 204 in the first second of stimulation. In normal leech saline, brief depolarizing current pulses (1 s) injected into cell 204 failed to elicit swim episodes. Following exposure to serotonin, however, identical pulses consistently evoked swim episodes. Thus, serotonin appears to transform cell 204 from a gating to a trigger cell. Serotonin had little effect on the steady-state current-voltage relation of cell 204. However, serotonin altered the membrane potential trajectories in response to injected current pulses and increased the amplitude of rebound responses occurring at the offset of current pulses. These changes suggest that serotonin modulates one or more voltage dependent conductances in cell 204, resulting in a more rapid depolarization and greater firing rate in response to injected currents. Thus, modulation of intrinsic ionic conductances in cell 204 may account in part for the increased probability of swimming behavior induced by serotonin in intact leeches. PMID- 8478816 TI - Gilles de la Tourette syndrome: a neuropsychiatric disorder. AB - Gilles de la Tourette Syndrome is a neuropsychiatric disorder which manifests with neurological psychological and psychiatric symptoms. Understanding of this complex disorder has grown rapidly in the past 25 years. This paper reviews the current knowledge of biological and psychological factors which interact to produce a variable yet clearly recognisable syndrome. New directions for research are explored. Current literature suggests that despite many gains, much remains to be learned about this disorder. PMID- 8478817 TI - Association between physical and psychological morbidity in the Whitehall II Study. AB - Mechanisms for the association between psychiatric disorder measured by the General Health Questionnaire and subjective and objective indices of physical illness are examined among 6900 male and 3414 female civil servants aged between 35 and 55 yr from the cross-sectional results of the Whitehall II Study. It was hypothesized that the association between physical illness and psychiatric disorder might be because psychiatric disorder was either secondary to the pain and disability of physical illness, or related to the somatic presentation of psychiatric disorder, or to common causes of both physical and psychiatric illness. Overall health status, and self-reported physical symptoms were strongly associated with psychiatric disorder. Angina in men and severe chest pain in men and women were significantly associated with psychiatric disorder, but electrocardiographic abnormalities were not. Established risk factors for physical illness: alcohol intake in women and men and smoking habit in men were related to psychiatric disorder. Fibrinogen was related to self reported physical symptoms but not psychiatric disorder. The association between psychiatric disorder and self-reported physical symptoms is most likely explained by somatisation and plaintive set. However, psychiatric disorder is likely to be secondary to the pain and disability of conditions such as angina. PMID- 8478818 TI - Osteoporosis and normal weight bulimia nervosa--which patients are at risk? AB - This study assesses the degree of bone mineral loss in women with active DSM IIIR bulimia nervosa. The subjects in this study were 20 GP-referred female patients of normal weight who met criteria for bulimia nervosa and 16 healthy age, sex and weight matched controls. Dual energy X-ray densitometry of lumbar L1-L4 vertebrae was performed on all subjects. The patients with bulimia nervosa had a significantly lower mean lumbar bone mineral density (0.964 g/cm2) than the control group (1.043 g/cm2, p < 0.01). Within the patient group only subjects with a past history of anorexia nervosa had a significantly lower mean bone mineral density (BMD) than the controls. Small sample sizes limit the power of the study, however significant correlations were found between duration of amenorrhoea, low BMI and lumbar BMD. Bulimic patients do suffer from osteoporosis. Risk factors for this may be; a past history of anorexia nervosa, prolonged secondary amenorrhoea, and a persistently low body mass index. PMID- 8478820 TI - Evidence against multiple premenstrual syndromes: results of a multivariate profile analysis of premenstrual symptomatology. AB - The topic of a single vs multiple premenstrual syndromes has generated much discussion. In this study, multivariate profile analysis was used to determine whether or not physical and affective symptoms associated with the premenstrual syndrome (PMS) could be explained as the manifestation of one underlying pathophysiologic process. The premenstrual symptom profiles of 820 undergraduate students and 485 graduate students were evaluated. It was not possible to reject the null hypothesis of parallel profiles in most comparisons, suggesting that variability in the severity of premenstrual symptoms may be the result of individual differences in the expression of one underlying pathophysiologic process. PMID- 8478819 TI - Relationship of cardiovascular reactivity and anger expression to serum lipid concentrations in healthy young men. AB - The relationship between behaviorally evoked cardiovascular reactivity, preferred mode of anger expression, and serum lipid concentrations was examined in 63 healthy, young adult males. Subjects derived from three studies, each evaluating cardiovascular response to laboratory stressors. All participants completed the Spielberger Anger Expression Scale and provided fasting blood samples for lipid determinations. A significant negative correlation, calculated by meta-analytic procedures, was noted between a baseline-free measure of heart rate reactivity and high density lipoprotein-cholesterol (HDL-C) concentrations (r = -0.26, p = 0.05). However, the previously reported relationship between cardiovascular reactivity and elevated total serum cholesterol (TSC) was not found. Additionally, men scoring high on a self-report measure of the tendency to express anger outwardly had significantly higher HDL-C concentrations than men scoring low on this measure (r = 0.30, p = 0.02); when subjects were stratified by level of cardiovascular reactivity, this relationship was apparent only among those showing the greatest magnitude of heart rate and blood pressure responses to acute mental stress. PMID- 8478821 TI - Improvement of respiratory function in chronic asthmatic patients with autogenic therapy. AB - Stress, unpleasant emotions and autonomic imbalance may play a main role in precipitating asthmatic attacks. In this study two homogeneous groups of asthmatic patients (N = 24) are treated over an eight-month period. The experimental group was treated with autogenic therapy and the control group with supportive group psychotherapy. Respiratory function parameters measured were Forced Vital Capacity (FVC), Forced Expiratory Volume in the first sec (FEV1), Forced Expiratory Flow between 25% and 75% of the FVC (FEF25-75%), and Mesoexpiratory Flow (MEF50%). The group under Autogenic Therapy obtained a relevant clinical improvement (> 15% of pretreatment values) in respiratory function. No significant changes were observed in the control group. These results suggest that autogenic therapy could be an effective adjunctive treatment in bronchial asthma. PMID- 8478822 TI - Psychosocial status in pre-adolescent children with beta-thalassaemia. AB - Psychiatric disorders and social profile were investigated in 57 children with beta-thalassaemia and 57 control subjects. Although there was no significant difference in the number of individuals with psychiatric disorders between the two groups, the number of psychiatric disorders observed in the group of patients was significantly greater than in the control subjects (p < 0.01). Oppositional defiant disorder (ODD) was diagnosed in 23% of the thalassaemics and in 5% of the control subjects (p < 0.01). The frequency of ODD in male patients (38%) was significantly greater than in female (7%) (p < 0.01). Thalassaemic patients demonstrated a significantly greater frequency of disturbed behavior with relatives and friends than the control subjects (p = 0.0005). This behavior was related to ODD. Also, thalassaemic patients with ODD showed a significantly higher serum ferritin level than thalassaemics without ODD (p < 0.005). This was attributed to non-compliance to treatment. No association of ODD with another haematological parameter was found. ODD is the major psychiatric disorder appearing in thalassaemic pre-adolescent children warranting psychiatric intervention. PMID- 8478823 TI - Discordance between symptom and physiological criteria for the hyperventilation syndrome. AB - Hyperventilation is assumed to produce a set of somatic and psychological symptoms, the so-called Hyperventilation Syndrome (HVS). Recognition of symptoms during the hyperventilation provocation test (HVPT) is the most widely used criterion for diagnosing HVS, but additional physiological and symptom criteria have been proposed. The concordance of various diagnostic criteria for HVS is investigated in the present study. Forty-eight psychiatric patients with panic disorder and 90 somatic patients with symptoms suspective of HVS performed a HVPT. There was a strong interrelationship between the various symptom criteria as well as the physiological criteria. However, almost no association between symptom and physiological HVS criteria were found. Symptom recognition was significantly related to trait anxiety, agoraphobia and depression. These data do not only question the validity of the HVPT, but also of the concept of HVS. The results are more consistent with a cognitive approach to anxiety in which the HVPT is seen as an aspecific stressor during which more anxious patients anticipate an anxiety attack. PMID- 8478824 TI - Associations between mood and specific health composites during U.S. Navy Persian Gulf operations. AB - Previously conducted field studies using shipboard U.S. Navy personnel during at sea operations in the Persian Gulf have shown that crew members experience mood changes and degradations in general physical health. The objectives of this study were to: (a) examine the relationship between mood and health complaints among personnel deployed in the Persian Gulf; and (b) extend previous research using specific health composites rather than a general measure of health. Mood was assessed for 104 shipboard volunteers using the Profile of Mood States Tension/Anxiety and Fatigue subscales. Health symptoms were measures using the Environmental Symptoms Questionnaire. Results of multiple regression analyses showed that each of 11 distinct health composites was significantly associated with one or both mood variables. Further, the two mood factors were differentially associated with 9 of the 11 health composites. This study underscores the usefulness of employing multiple specific health measures rather than global measures. PMID- 8478825 TI - Pain thresholds during standardized psychological stress in relation to perceived psychosocial work situation. Stockholm Music I Study Group. AB - The hypothesis that perceived psychosocial work situation is associated with pain threshold was tested on a sample of 103 men and women aged 19-65 yr in Stockholm. Half of the studied sample was a random sample of men (N = 26) and women (N = 31), while the remaining subjects were medical secretaries (women, N = 28) and furniture movers (N = 31). Pain thresholds were measured by means of an algometer before, during and after a standardized colour word test. The measurements were made on six different points in the neck and shoulder region. Before psychological stress in the laboratory, perceived psychological demands were significantly associated with pain threshold--the higher the demands the higher the pain threshold. During stress those who reported low decision latitude and high degree of sleep disturbance were shown to have a low pain threshold. The findings are consistent with the hypothesis that subjects with high demand levels have an elevated pain threshold when they are not under excessive psychological stress. During psychological stress, on the other hand, those with low decision latitude are more pain sensitive than others, and this is aggravated in those who also report a high degree of sleep disturbance. PMID- 8478826 TI - Leg lengthening. AB - The combined experience of the Royal Hospital for Sick Children, Glasgow and the Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry in lengthening 52 lower limb segments with the Orthofix device is reviewed. Forty-eight segments were lengthened by callotasis, 24 in patients with achondroplasia. Attempted lengthening with chondrodiatasis was performed in 4 patients with leg length discrepancy. With callotasis, planned lengthening was achieved in 43/48 (90%) of segments. There was a small number of significant complications. Angulation or buckling of the new bone was the commonest major complication, and was seen in 10% of segments. Pin tract infection was the predominant minor complication. Premature union was noted commonly in the femurs of achondroplastics, but could usually be overcome with manipulation under anaesthesia. We confirm that callotasis achieves its objectives with fewer complications and operations than the commonly used Wagner method which it should supersede. By contrast, we had major complications in all cases with chondrodiatasis and have abandoned this method. PMID- 8478827 TI - Bilateral knee replacements: simultaneous or staged? AB - Approximately one-third of primary knee replacements are performed on patients with bilateral symptomatic disease. This retrospective study compared the complication rate, functional outcome and cost implications of performing bilateral total knee replacements under a single anaesthetic or as staged procedures with a control group of unilateral cases. There was no significant difference in the complications or outcome. There was a significant reduction in the mean hospital admission time of 7 days per knee replacement (P < 0.001, Student's t test) by performing bilateral knee replacements for osteoarthritis under the same anaesthetic. However, a survey of practising knee surgeons in three health regions in the United Kingdom shows that only 24% would regularly perform bilateral knee replacements under one anaesthetic. PMID- 8478828 TI - A clinicopathological study of idiopathic CTEV. AB - Clubfeet were assessed preoperatively, intra-operatively, postoperatively and histologically. There appeared to be a variety of distinct pathobiological groups. A type I/type II fibre area ratio of equal to or greater than 0.9 may be of prognostic value. PMID- 8478829 TI - What do orthopaedic surgeons tell patients? AB - Surgical patients have the right to clear communication regarding diagnosis, treatment and prognosis including risks and likelihood of success. In order to ascertain the level of consensus which exists among orthopaedic surgeons about what patients should be told, a short questionnaire comprising a fictitious case history of a candidate for total hip replacement and a list of sample statements was mailed to all orthopaedic surgeons in Northern Ireland; 86% replied. Surgeons were in general agreement about what the patient should and should not be told prior to operation. This approach may be adapted for other procedures. PMID- 8478830 TI - Elbow dislocation with intra-articular entrapment of the lateral epicondyle. PMID- 8478831 TI - Reducing skin exposure to methylmethacrylate: a description of technique. PMID- 8478832 TI - Modified AO bone clamp used as a distractor. PMID- 8478833 TI - An alternative soft tissue protector for intramedullary nailing. PMID- 8478834 TI - HRT and the surgeon. Guidelines from the Royal College of Surgeons of Edinburgh (November 1992). PMID- 8478835 TI - Thyroid surgery without drainage: 15 years of clinical experience. AB - Drainage in thyroid surgery has been a routine but empirical practice with no scientific evidence to support its benefit. The largest series to date of non drainage in thyroid surgery is presented, comprising 260 patients over a 15-year period. No case selection for non-drainage was employed. Two hundred and fifty nine cases were not drained and included toxic goitres, and bilateral and redo procedures. There was one thyroid storm and two cases of subcutaneous fluid collection, treated by needle aspiration. No cases of recurrent laryngeal nerve injury, airway obstruction or death were recorded. This study strongly demonstrates the safety of non-drainage in routine thyroid surgery. PMID- 8478836 TI - Combined predeposit and salvage autotransfusion in elective aortic aneurysm repair. AB - In this study assessing the safety and value of the routine use of autotransfusion in elective aortic aneurysm surgery, the first 16 patients (control group) received homologous transfusion only, while the subsequent 38 patients (autotransfusion group) received a combination of predeposit and salvage autotransfusion (Solcotrans device). Between 1 and 3 units of blood were venesected preoperatively, and a median of 0.80 (0.20-2.75) litres of unwashed shed blood was salvaged and re-infused (48% of the measured blood loss). A median of 4 units of banked blood was required in the control group compared with 2 units in the autotransfused group, an average saving of 2 units per patient (P < 0.001). Banked blood was avoided completely in 37% of patients in the autotransfusion group. There were no haematological or biochemical complications. Predeposit and salvage autotransfusion is simple and safe, and reduces banked blood requirement in aortic aneurysm surgery. PMID- 8478837 TI - Experience with breast cancer in Zimbabwe. AB - Eighty-four patients were treated for carcinoma of the breast at Mpilo Central Hospital, Bulawayo, between July 1987 and December 1990. The age at diagnosis appears to be bimodal with an early peak between 35 years and 40 years and a later peak between 60 years and 65 years. As expected, these patients were of high parity (median 5) and 96% of them breast fed for an average of 16 months. It would appear that late presentation with advanced systemic disease accounts for the dismal prognosis. Eighty-four per cent of the patients presented with late disease with only 16% presenting with early disease. Of the 25 patients who were followed to death the median survival was 12 weeks. For various logistic reasons long-term follow-up has not been possible for the rest of the patients. The expense involved in travelling long distances appears to be the main problem. To improve the outcome of breast cancer in our community we we need to embark on an active education campaign to increase public awareness of the significance of breast symptomatology. However, the incidence of carcinoma of the breast in this part of the world remains very low when compared with experience in Western countries. PMID- 8478838 TI - Cholecystectomy: a study of patient satisfaction. AB - A prospective study of 77 patients undergoing open cholecystectomy was undertaken to establish the degree of satisfaction experienced by these patients. Specific symptoms were recorded preoperatively and at one year postoperatively. Two patients died from unrelated diseases during the year of follow-up and were excluded from the analysis. All symptoms inquired about reduced in frequency postoperatively, the best cures being achieved for jaundice, upper abdominal colic, fatty food intolerance and back/shoulder pain. A third of patients developed at least one new symptom during the year of follow-up. Seventy-seven per cent graded themselves either completely or well satisfied. It was not possible to predict from preoperative symptoms those who would be dissatisfied or those who would develop a new symptom. This study refutes recent suggestions that up to 50% of patients are dissatisfied with cholecystectomy and provides data which may be used to counsel patients preoperatively. PMID- 8478839 TI - Omentoplasty versus introflexion for hydatid liver cysts. AB - Forty-three patients with unilocular hydatid cyst of the liver were divided into three groups. Omentoplasty (n = 15) was performed in group 1, introflexion (n = 18) in group 2 and a combination of both (n = 10) in group 3. Patients with omentoplasty developed fewer complications and had a significantly shorter hospitalization than those with introflexion. The results indicate that omentoplasty is superior both to introflexion and to introflexion plus omentoplasty for the management of hydatid liver cysts. PMID- 8478840 TI - Open biliary surgery and the use of routine inpatient audit. AB - 'Morbidity profiles' offer a practicable and effective method of assessing overall surgical performance. In this study they have been used to document the results of elective and emergency open biliary surgery carried out on 246 consecutive patients over a 2-year period. The results demonstrate that such surgery for the treatment of cholelithiasis and its complications is extremely safe. There was one postoperative death (0.4%) and an in-hospital major morbidity rate of 4.6%. Minor morbidity was common, especially in the elderly and following emergency surgery. The data presented here will be of particular interest to the increasing number of surgeons advocating laparoscopic biliary surgery. PMID- 8478841 TI - Effect of bowel cleansing and colonoscopy on serum CEA levels. AB - A group of patients being investigated for various forms of colonic pathology showed an apparent rise in serum carcinoembryonic antigen (CEA) level following bowel cleansing at the time of colonoscopy, as compared with the 'resting' level. The rise was particularly marked in a small group of patients with colonic polyps or previous colonic resection for carcinoma, suggesting a need for careful timing in the taking of blood samples. The findings may also have diagnostic importance in identification of patients at higher risk of malignant disease of the colon. PMID- 8478842 TI - Avoidable complications of arthroscopic surgery. AB - The incidence of complications from arthroscopic surgery is low. Between 1978 and 1991, 8500 arthroscopies were performed by the two senior authors (J.N. and D.R.A.D.). Several significant complications were recorded, and these are presented to show how they occurred, and how our practice of arthroscopy was subsequently modified. There were four cases of clinically detectable deep vein thrombosis of which three were associated with pulmonary embolus, three cases of haemarthrosis, two deep infections, three compartment syndromes with one case of impending compartment syndrome, six cases of instrument failure and one case of persistent synovial fistula. PMID- 8478843 TI - Removal of metal implants after fracture surgery--indications and complications. AB - In a study of 297 internal fixation operations for fractures or joint injuries performed during 1982, a second operation for implant removal was undertaken in 42% of cases. Significant complications occurred following the second procedure in 19%. Implants which were retained did not give rise to appreciable problems. It is suggested that implants should only be removed when there are clear clinical indications for doing so. PMID- 8478844 TI - Platonic outcomes. PMID- 8478845 TI - Hyperimmune fatigue syndromes: diseases of the stress response? PMID- 8478846 TI - The contribution of human c-fos DNA to cultured synovial cells: a transfection study. AB - To clarify the role of c-fos DNA in the activation of human synovial cells, the pH8 expression vector containing human c-fos DNA under the control of murine leukemia virus long terminal repeat was transfected into cultured synovial cells. After G418 selection, the control transfectant clones transfected with pH8 vector not containing c-fos DNA insertion changed their original fibroblastic shape into dendritic cells. They stopped growing at this stage. However, the c-fos DNA transfectant clones continued to grow actively beyond this stage, and regained the fibroblastic appearance. Furthermore, c-fos DNA transfectants adhered to and grew on hyaluronidase treated cartilage surfaces more extensively than control transfectants after 6 days in culture. These findings suggest that c-fos DNA supports active growth of human synovial cells by facilitating transition of synovial dendritic cells into fibroblastic cells. PMID- 8478847 TI - A comparison of the sensitivity to change of several health status instruments in rheumatoid arthritis. AB - We carried out a study to compare the sensitivity to change of disease specific compared with more generic health status instruments in relation to rheumatoid arthritis (RA). A sample of 102 patients was recruited and assessed by means of 4 health status instruments and standard rheumatological measures on 3 occasions separated by 3 monthly intervals. Sensitivity to change for mobility, activities of daily living, household, pain, emotions and social dimensions were calculated. For some dimensions disease specific health status instruments performed less well. However overall there was no evidence of consistent differences between the 2 approaches. We conclude that generic instruments have a role in the assessment of RA. PMID- 8478848 TI - Influence of disease duration, continued followup and further antiphospholipid testing on the frequency and classification category of antiphospholipid syndrome in a cohort of patients with systemic lupus erythematosus. AB - In an earlier study of a cohort of 667 patients with systemic lupus erythematosus (SLE) followed for 7.5 months with mean antiphospholipid (aPL) testing 2.5 times, we found a 10% prevalence of definite antiphospholipid syndrome (APS) (2 clinical manifestations and high aPL levels). To determine if more followup and aPL testing increased such prevalence we restudied the cohort after a mean followup of 3.1 years and a mean aPL testing of 5.6 times and found a 15% prevalence of definite APS. Another 21% of patients with SLE had probable APS with either high titers of aPL but only one clinical manifestation or low titers with 2 clinical manifestations. The prevalence of high titer positivity of aPL (IgG and/or IgM isotype) reached 41%. One aPL related feature that increased significantly was livedo reticularis possibly from increased awareness. Factors that influenced significantly the mobility upwards in APS category were more pregnancies and further aPL testing. Conversely, immunosuppressive treatment decreased higher aPL levels. The large number of patients with long disease duration in our cohort showed that the maximum prevalence of definite APS is reached after 15-18 years and is 23%. This might be the highest prevalence of definite APS within SLE. PMID- 8478849 TI - Complement component C4A and C4B levels in systemic lupus erythematosus: quantitation in relation to C4 null status and disease activity. AB - Immunoassays using C4 monoclonal antibodies were developed to quantitate C4A, C4B and total C4 in the serum of healthy controls and patients with systemic lupus erythematosus (SLE). Mean C4A or C4B levels were reduced when a single C4A*Q0 or C4B*Q0 gene was present; however, total C4 levels showed considerable overlap with and did not differ significantly from the non-C4 null groups in either patients or controls. Black patients with SLE without active disease, as well as black controls, had higher levels of C4B and consequently total C4 than whites. Ten patients with SLE studied serially showed that C4A and C4B levels changed proportionally during changes in disease activity. Thus, it may be more important to consider race and disease activity rather than C4 null gene status when assessing C4 levels in patients with lupus. PMID- 8478850 TI - Arthritis in hemochromatosis. AB - We reviewed the clinical and radiographic features of arthropathy in 25 subjects with hemochromatosis, 16 probands and 9 discovered homozygous relatives. Clinical arthritis was present in 15/16 probands and 1/9 discovered homozygotes (p < 0.005). Radiologic evidence of arthropathy was seen additionally in 2 asymptomatic discovered homozygotes. The metacarpophalangeal joints and wrists were most commonly involved; severe hip disease occurred in 6. Patients with clinical or radiologic arthropathy were older than patients without. Arthropathy occurred in all 4 female probands, but in none of the 3 female discovered homozygotes. Chondrocalcinosis was seen in 9 subjects but was usually asymptomatic. The arthritis of hemochromatosis may be difficult to differentiate from several other joint diseases, especially calcium pyrophosphate dihydrate deposition disease. PMID- 8478851 TI - Suprascapular nerve block for persistent rotator cuff lesions. AB - The suprascapular nerve supplies sensory nerves to the posterosuperior aspect of the shoulder, including major portions of the rotator cuff. Suprascapular nerve block using steroid/bupivacaine is temporarily effective in reducing pain in rotator cuff tendinitis and tears, improving movement range in tendinitis and is possible in an outpatient setting with little or no complication risk. PMID- 8478852 TI - A double-blind trial of the clinical effects of pulsed electromagnetic fields in osteoarthritis. AB - OBJECTIVE: Further evaluation of pulsed electromagnetic fields (PEMF), which have been observed to produce numerous biological effects, and have been used to treat delayed union fractures for over a decade. METHODS: In a pilot, double-blind randomized trial, 27 patients with osteoarthritis (OA), primarily of the knee, were treated with PEMF. Treatment consisted of 18 half-hour periods of exposure over about 1 month in a specially designed noncontact, air-coil device. Observations were made on 6 clinical variables at baseline, midpoint of therapy, end of treatment and one month later; 25 patients completed treatment. RESULTS: An average improvement of 23-61% occurred in the clinical variables observed with active treatment, while 2 to 18% improvement was observed in these variables in placebo treated control patients. No toxicity was observed. CONCLUSION: The decreased pain and improved functional performance of treated patients suggests that this configuration of PEMF has potential as an effective method of improving symptoms in patients with OA. This method warrants further clinical investigation. PMID- 8478853 TI - The risk of osteoarthritis with running and aging: a 5-year longitudinal study. AB - Our purpose was to determine the 5-year longitudinal effects of running and aging on the development of radiographic and clinical osteoarthritis (OA) of the knees, hands and lumbar spine. Thirty-five running subjects and 38 controls, with a mean age of 63 years, were matched for age (+/- 2 years), years of education, and occupation; 33 matched pairs were constructed. All subjects underwent rheumatologic examination, completed questionnaires, and had radiographs taken of the hands, lateral lumbar spine, and knees in 1984 and in 1989. Five year radiographic results for both the runner and control groups showed OA progression for the knees, hands, and lumbar spine. In 1989, 10 (13%) of the 73 subjects fit American College of Rheumatology (ACR) criteria for clinical OA of the hand, and 9 subjects (12%) fit ACR criteria for OA of the knee. In summary, running did not accelerate the development of radiographic or clinical OA of the knees, but with aging, 13% of all subjects developed OA of the hands and 12% of all subjects developed OA of the knees. PMID- 8478854 TI - Fibromyalgia and quality of life: a comparative analysis. AB - The quality of life of women with fibromyalgia was explored and compared to the quality of life of women with rheumatoid arthritis, osteoarthritis, permanent ostomies, chronic obstructive pulmonary disease, insulin dependent diabetes, and healthy controls. The women with fibromyalgia consistently scored among the lowest in all domains measured. These results suggest that fibromyalgia may adversely affect quality of life to an extent not previously recognized. PMID- 8478855 TI - Risk factors for physical disability in an aging cohort: the NHANES I Epidemiologic Followup Study. AB - Successful improvement in health in our increasingly aged population will depend in substantial part on reduction of age specific disability levels. In turn, the epidemiologic model suggests that this requires identification of risk factors, development of intervention models, and testing of these models. We attempted to identify risk factors for physical disability among 4,428 50-77-year-olds using baseline data collected in the first National Health and Nutrition Examination Survey (NHANES I) (1971-1975) linked to disability data collected 10 years later in the NHANES I Epidemiologic Followup Study. Results of forward stepwise linear regression analysis showed that the major characteristics contributing to greater disability (explaining at least 1% of the variability in scores) were older age at baseline, less nonrecreational activity, arthritis history, less education, female sex, and greater body mass index at age 40. Other factors associated with greater disability included a history of asthma, cardiovascular disease, abnormal urine test, less recreational activity, higher sedimentation rate, rheumatic fever history, lower caloric intake, positive musculoskeletal findings, histories of polio and allergies, lower family income, elevated blood pressure, lower serum albumin, history of tuberculosis, glucose in the urine, and histories of hip or spine fracture, chronic pulmonary disease, and kidney disease. PMID- 8478856 TI - Treatment of systemic lupus erythematosus by prolonged administration of high dose intravenous immunoglobulin: report of 2 cases. AB - Two patients with life threatening manifestations of systemic lupus erythematosus (SLE), unresponsive to corticosteroid and immunosuppressive therapy, were treated with high dose intravenous immunoglobulin (IVIG). Following IVIG therapy, lupus pneumonitis and encephalitis in the first patient, and lupus nephritis in the second patient, resolved. Continuous treatment with IVIG, every 4 weeks for up to 20 months induced a prolonged clinical and laboratory remission. Treatment with cytotoxic agents was stopped, and the dosage of corticosteroids lowered. Exacerbation of lupus nephritis occurred in the second patient after 10 months of IVIG therapy. We suggest that prolonged use of high dose IVIG may be a useful therapy for acute exacerbations of SLE and for inducing prolonged remissions. PMID- 8478857 TI - First case of pneumatosis cystoides intestinalis in adult dermatomyositis. AB - We describe the first case of pneumatosis cystoides intestinalis in dermatomyositis (DM) of an adult. Our patient had been in remission of her DM for years when pneumatosis cystoides intestinalis occurred. Discovery of it was concomitant with that of interstitial lung disease. The overall course of pneumatosis cystoides intestinalis was benign. We discuss the mechanism of bowel and lung involvement and hypothesize that vasculitis could be the underlying process. PMID- 8478858 TI - Respiratory failure in Wegener's granulomatosis: response to pulse intravenous methylprednisolone and cyclophosphamide. AB - We describe a patient with respiratory failure due to Wegener's granulomatosis (WG) who obtained a dramatic and sustained response to pulse intravenous methylprednisolone and cyclophosphamide. Discussion includes a review of the literature with respect to the relative merits of daily oral cyclophosphamide versus pulse intravenous cyclophosphamide in WG and other vasculitides. While the combination of daily oral steroids and daily oral cyclophosphamide dramatically improves the outcome of WG, this therapy is not without serious side effects. Pulse therapy may be equally as effective and may lessen the frequency of serious side effects. PMID- 8478859 TI - Bronchocentric granulomatosis, acute renal failure, and high titer antineutrophil cytoplasmic antibodies: possible variants of Wegener's granulomatosis. AB - We describe 2 patients with clinical syndromes suggestive of Wegener's granulomatosis: elevated titers of cytoplasmic antineutrophil cytoplasmic antibodies (cANCA), bronchocentric granulomatosis, and acute renal failure. A renal biopsy in one case showed crescentic glomerulonephritis and in the other case showed interstitial nephritis. These cases may reflect bronchocentric granulomatosis among a spectrum of diseases associated with cANCA. Use of cANCA may identify those patients with bronchocentric granulomatosis who require immunosuppressive therapy. PMID- 8478860 TI - Uncommon origin for the iliopsoas sign. AB - The term "iliopsoas sign" has different meanings in the medical literature. Among musculoskeletal disorders, iliopsoas bursitis is probably the most common cause of this clinical sign. Here we report an unexpected vascular pathology in a young man. The only clinical manifestation on examination was an iliopsoas sign. PMID- 8478861 TI - Osteomalacia in a patient with anorexia nervosa. AB - A 32-year-old patient with anorexia nervosa since adolescence was admitted because of diffuse bone pain, increasing during the 2 preceding winters. She had a special aversion to dairy products and all forms of dietary fat. Low normal serum calcium and very low calciuria were noted, with a highly elevated bone fraction of alkaline phosphatase, and severe hypovitaminosis D and B12. Apart from a recent spontaneous fracture of the clavicle, Looser lines and pseudofractures were noted in a finger, fibula and malleolus. In particular, magnetic resonance imaging of the knee showed additional evidence of a pseudofracture in the femur, and medullary changes were found. Evidence for secondary hyperparathyroidism was described. Apart from the well known occurrence of osteoporosis, our case shows that osteomalacia may exceptionally occur in anorexia nervosa. PMID- 8478862 TI - Pyomyositis and septic arthritis from Fusobacterium nucleatum in a nonimmunocompromised adult. AB - We describe a case of pyomyositis of the quadriceps associated with septic arthritis of the knee that developed after Fusobacterium nucleatum septicemia in a healthy man. The primary foci was presumed to be the oral cavity. Pyomyositis from Fusobacterium nucleatum is uncommon, and to our knowledge its association with septic arthritis has not been described. PMID- 8478863 TI - Pyomyositis: early detection and treatment. AB - We describe a patient with Crohn's disease and pyomyositis due to Streptococcus anginosus ("milleri"). Early recognition of pyomyositis during its presuppurative phase allowed for prompt antibiotic treatment and rapid resolution of the muscle infection without surgical drainage. PMID- 8478864 TI - OMERACT conference on outcome measures in rheumatoid arthritis clinical trials: introduction. PMID- 8478865 TI - Choosing a core set of disease activity measures for rheumatoid arthritis clinical trials. AB - Rheumatoid arthritis (RA) clinical trials often include at least 10 measures of disease activity (e.g., tender and swollen joint counts, erythrocyte sedimentation rate, patient pain, grip strength, etc.), and each trial contains different measures. Using dissimilar disease activity (outcome) measures to assess therapies makes it impossible to judge therapies against a common standard. Furthermore, multiple statistical testing is performed, and outcome measures are often used which are insensitive to change. Ultimately, to compare different RA therapies, the same outcomes should be measured in all trials. In the first stage of an effort to develop a core set of outcome measures to be used in all RA trials, we present an approach to the selection of the measures. This approach is based on a critical evaluation of whether commonly used outcome measures have construct, face, content, criterion, and discriminant validity. In addition, our approach includes testing whether these measures are redundant. Also, selected evidence on the validity of currently used outcome measures is reviewed. PMID- 8478866 TI - Sensitivity to change of rheumatoid arthritis clinical trial outcome measures. AB - OBJECTIVES: To present the properties of an efficiency measure that may be used to make statistical comparisons of sensitivities of trial outcome measures. To use this measure to examine the relative sensitivities of several common rheumatoid arthritis (RA) trial outcome measures in 2 different trial settings. METHODS: Efficiency is expressed as the mean change divided by the standard deviation of change. Variability and correlations of efficiencies for typical RA trial outcomes are described. RESULTS: From among a variety of joint assessments and other clinical measures, pain and global measures, and health status and laboratory measures, the joint tenderness and pain measures were the most sensitive, both in a trial of nonsteroidal antiinflammatory drugs (NSAID) and in a set of second-line drug trials. Measures with rather different sensitivities in the 2 types of trials were erythrocyte sedimentation rate (low sensitivity in the NSAID trial) and physician and patient global measures (higher sensitivity in the NSAID trial). CONCLUSION: The use of statistical information on efficiency estimates allows for a variety of comparisons of measures and may inform the selection of outcome measures for clinical trials. PMID- 8478867 TI - European preferences in assessing rheumatoid arthritis. PMID- 8478868 TI - Outcome measures in rheumatoid arthritis clinical trials: assessing improvement. PMID- 8478869 TI - The hierarchy of outcome assessment. PMID- 8478870 TI - A method for achieving consensus on rheumatoid arthritis outcome measures: the OMERACT conference process. AB - We describe the process used during the international Conference on Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). The objectives of the conference were (1) to broaden consensus on the minimum number of outcome measures to be included in all RA clinical trials in rheumatoid arthritis (RA); (2) to achieve consensus on criteria for (a) minimum clinically important improvement in patients with RA and (b) minimum important differences between treatment groups in RA clinical trials; and (3) to decide whether aggregate outcome measures (indices) are useful in the assessment of patients and trials. A combination of plenary sessions and structured nominal groups were employed during the conference. Simulated patient profiles and clinical trial profiles were used to generate discussion. The objective of the nominal group exercises was to capture each participant's judgments of the relative importance of each outcome measure and the degree of change required to indicate clinical improvement. Considerable discussion ensued on the content of the core set of outcome measures. An electronic interactive voting machine was used to obtain participants' views on a core set of outcome measures and methodological issues. To permit further discussion of outcome measures, the group explored the use of aggregate outcome measures (indices) in patient care and trials only in a preliminary way. A final plenary session dealt with patient perceptions of minimum important differences, a new classification of antirheumatic drugs, and a repeat of part of the preconference questionnaire. Concluding statements and future plans were developed at the conclusion of the meeting. PMID- 8478871 TI - OMERACT conference questionnaire results. OMERACT Committee. AB - Just prior to the OMERACT conference, participants completed a questionnaire that solicited explicit opinions on the issues discussed at the conference. The response rate was 77%. To determine the minimum level of important difference in a clinical trial comparing 2 active drugs, participants were asked to think of each of 6 separate measures in turn as designated primary outcome measure. In this situation, to decide that an important difference between the 2 groups was present, participants required a median of 20% difference in painful joints, swollen joints, and in disability, 30% in pain and patient global assessment, and 40% in physician global assessment. On each measure, between 3 to 12% of participants felt they could not decide on an important difference in that situation. Similar questions were asked for the minimum important improvement in a patient; required levels of improvement were similar but slightly higher than the responses given for trials, and more participants felt they could not decide. Correspondents indicated that acute phase reactants are also very important for assessing minimum levels of important difference and improvement in trials and patients. A large majority was in favor of applying an index of aggregated outcome measures if sensible and valid: 72% in patients, and 93% in trials. PMID- 8478872 TI - Developing consensus on preliminary core efficacy endpoints for rheumatoid arthritis clinical trials. OMERACT Committee. PMID- 8478873 TI - Minimum important difference between patients with rheumatoid arthritis: the patient's perspective. AB - OBJECTIVE: To determine the point at which differences in clinical assessment scores on physical ability, pain and overall condition are sufficiently large to correspond to a subjective perception of a meaningful difference from the perspective of the patient. METHODS: Forty patients with a diagnosis of rheumatoid arthritis participated in an evening of clinical assessment and one-on one conversations with each other regarding their arthritic condition. The assessments included tender and swollen joint counts, clinician and patient global assessments, participant assessment of pain and the Health Assessment Questionnaire (HAQ) on physical ability. After each conversation, participants rated themselves relative to their conversational partner on physical ability, pain and overall condition. These subjective comparative ratings were compared to the differences of the individual clinical assessments. RESULTS: In total there were 120 conversations. Generally participants judged themselves as less disabled than others. They rated themselves as "somewhat better" than their conversation partner when they had a (mean) 7% better score on the HAQ, 6% less pain, and 9% better global assessment. In contrast, they rated themselves as "somewhat worse" when they had a (mean) 16% worse score on the HAQ, 16% more pain, and 29% worse global assessment. CONCLUSIONS: Patients view clinically important differences in an asymmetric manner. These results can provide guidance in interpreting results and planning clinical trials. PMID- 8478874 TI - Criteria for clinically important changes in outcomes: development, scoring and evaluation of rheumatoid arthritis patient and trial profiles. OMERACT Committee. AB - OBJECTIVE: To further the development of criteria for clinically important changes in outcomes seen in rheumatoid arthritis (RA) patients and trials. METHODS: Small group discussions and voting on specially designed profiles based on a 6 factor 2 level factorial design for changes seen in patients and trials. The purpose was to bring out the implicit opinions of participants on these issues, to complement the explicit opinions expressed in the OMERACT questionnaire. This took place at a conference of rheumatologists, methodologists, biostatisticians, regulatory, pharmaceutical and biotechnology industry personnel with an interest in therapies for patients with RA. Data from patients with RA and randomized clinical trials of second line drugs in patients with RA formed the basis to create 64 patient profiles and 64 trial profiles. The profiles contained information on changes in 6 measures: swollen joint count, tender joint count, pain, patient global assessment, physician global assessment and physical disability. The profiles were prepared on 4" x 5" cards and presented to the participants in packages of 64 in random order, in 2 different group sessions. Participants were assigned to 8 groups that contained a mix of all types of participants, with a majority of clinicians in each group. In the patient profile session, individual participants scored whether the profile represented important improvement. In the trial profile session, participants did likewise for important difference between the drugs. After structured discussion the group then voted: consensus was defined as agreement by at least 70% of the group. We decided that an important improvement or difference was present in the profiles on which at least 6 of the 8 groups had achieved consensus. The changes in the profiles showing important improvement or difference can be used to suggest minimum criteria for each of the 6 measures. RESULTS: The lower quartile of the change present in the patient profiles with important improvement varied from 17% (swollen joints) to 49% (disability); the median of these quartiles was 36%. The lower quartile of the differences present in the trial profiles with important differences varied from 13% (tender joints) to 26% (physician global); the median of these quartiles was 18%. CONCLUSIONS: This approach has provided a beginning for less arbitrary definition of criteria for important change in patients and trials. It might be suggested that for patients, an improvement of at least 36% should be clinically important, while an active drug needs to be at least 18% better than placebo to be clinically important. PMID- 8478875 TI - Pooled outcome measures in arthritis: the pros and cons. AB - This article considers the implications of reporting multiple measures of efficacy in studies of patients with rheumatoid arthritis (RA). A possible solution to the problems that result is the use of a pooled index which combines the individual outcome measures. The potential advantages and disadvantages of pooled indexes are discussed in the context of clinical trials in RA. PMID- 8478876 TI - The validity of pooled outcome measures (indices) in rheumatoid arthritis clinical trials. AB - No consensus exists on the appropriate (set of) endpoints to be reported in rheumatoid arthritis clinical trials. The traditional endpoints are not comprehensive, show overlap, and are insensitive to change. A single, pooled outcome measure or index may be an alternative. However, such an index must be valid and acceptable. An overview of the existing indices suggests several options are available. To date, practical experience with these indices in trials is limited. PMID- 8478877 TI - Interpretation and power of a pooled index. AB - OBJECTIVE: To describe, illustrate, provide statistical rationale and give clinical examples of the concept of a pooled index. METHODS: No explicit design. Randomized control trials of patients diagnosed with rheumatoid arthritis from Rheumatic disease clinics, tertiary care hospitals and communities are used as examples to illustrate the pooled index technique. Interventions in rheumatic disease unit inpatient and outpatient care, occupational therapy and physiotherapy provided by Arthritis Society Therapists in the community were compared. Variables included active joint count, morning stiffness in min, mean of right and left grip strength in mm Hg, erythrocyte sedimentation rate in mm/h, a functional change score, and a pooled index. RESULTS: The pooled index in each study detected a clinically important effect while individual measures were generally not able to declare the effect statistically significant. CONCLUSIONS: The pooled index is a more powerful clinical outcome than any individual measure provided it is computed from at least 2 relevant clinical outcome measures that have low correlation with each other. PMID- 8478878 TI - Development of a disease activity score based on judgment in clinical practice by rheumatologists. AB - In a prospective study of up to 3 years' duration of 113 patients with early rheumatoid arthritis a disease activity score (DAS) was developed based on the clinical judgment of 6 rheumatologists. The patients were divided in groups with high and low disease activity according to explicit rules. By various statistical methods, including discriminant analysis and multiple regression analysis, a DAS could be defined. This DAS is a continuous measure consisting of the variables Ritchie articular index, number of swollen joints, erythrocyte sedimentation rate and general health measured on a visual analog scale. PMID- 8478879 TI - A simple index to assess disease activity in rheumatoid arthritis. AB - Changes in clinical and laboratory measures of disease activity were studied prospectively in 12 European centers. Altogether 282 rheumatoid patients were evaluated during 6 months of therapy with slow-acting drugs. Patients' global assessment was taken to indicate overall response. The number of swollen joints and number of tender joints correlated highly with this. The erythrocyte sedimentation rate (ESR) correlated less well but was more uniform across centers. Grip strength, C-reactive protein and hemoglobin performed poorly between centers. There were cultural and linguistic difficulties using the Health Assessment Questionnaire in a European setting. Physician's global assessments were similar to the patient's global assessments and provided redundant information. The best measures are: the number of swollen joints, the number of tender joints, the ESR, and the patient's global assessment. It may also help to measure articular pain. PMID- 8478880 TI - New classification of antirheumatic drugs. The evolution of a concept. PMID- 8478881 TI - OMERACT and the clinical evaluation of new therapeutic agents: a bird's eye view. OMERACT Committee. PMID- 8478882 TI - Treatment of pernicious anemia associated with systemic lupus erythematosus. PMID- 8478883 TI - Repetitive use of pulse therapy. PMID- 8478884 TI - Human T lymphotropic virus I, myelopathy, polymyositis and synovitis. PMID- 8478885 TI - Successful treatment of pulmonary hypertension associated with systemic lupus erythematosus with prostaglandin I2 and prostaglandin E1. PMID- 8478886 TI - Fibrous myopathy induced by propoxyphene injections. PMID- 8478887 TI - Erosive arthritis with dermatomyositis without elevated anti-Jo-1 antibodies and not associated with pain. PMID- 8478888 TI - Oral methotrexate in the treatment of Felty's syndrome. PMID- 8478889 TI - Remission in palindromic rheumatism during pregnancy. PMID- 8478890 TI - Thyroid disorder in patients with mixed connective tissue disease. PMID- 8478891 TI - Accidents in industry. PMID- 8478892 TI - A pilot study of diet and gallstone formation in young Saudi women. AB - The diet of 100 younger than 40 years Saudi females; 50 cases with gallstones and 50 control mean age and SD 30.2 (6.1) and 29.7 (6.4) years respectively, was studied by taking a qualitative dietary history. There was no significant difference between the dietary intake of the 2 groups with regard to cholesterol rich food and animal fat-rich foods, high fibre foods and the consumption of fast food. However, dates, 'kabsah', 'modabi' and cheese were consumed significantly more by cases (P-value < .001, < .046, < .001 and < .004 respectively) and vegetable oil was used more by controls for cooking purposes (P-value < .05). PMID- 8478893 TI - High perinatal and neonatal mortality in rural India. AB - A prospective study conducted in rural India on pregnant women showed poor utilization of primary health services and very poor maternal care receptivity especially in terms of antenatal care. A very high perinatal mortality rate of 81.3/1000 live births and a neonatal mortality rate of 63.7/1000 live births was observed in the present study. Out of 204 live births, 72.05% of newborn developed complications within 6 weeks of the delivery. Most of the complications were of a minor nature and could be attributed to poor environmental conditions, lack of personal hygiene and ignorance. The study highlights the need for training of grass root level workers for the improvement of perinatal and neonatal care in rural India. PMID- 8478894 TI - Socio-cultural and economic factors affecting food consumption patterns in the Arab countries. AB - Several factors have been found to determine the dietary habits of the people in the Arab world. Food consumption pattern has dramatically changed in some Arab countries as a result of sudden increase in income from oil revenue. It is believed that food subsidy policy has adversely affected the food habits in the Gulf states by encouraging the intake of fat, sugar, rice, wheat flour and meat. Socio-cultural factors such as religion, beliefs, food preferences, gender discrimination, education and women's employment all have a noticeable influence on food consumption patterns in this region. Mass media, especially televised food advertisements, play an important role in modifying the dietary habits. The migration movement, particularly that which was carried out during the 70s has a great impact on the food practices in many Arab countries. Comprehensive studies on social, cultural and economic factors associated with food consumption patterns in the Arab region are highly recommended. PMID- 8478895 TI - Nutritional and non-nutritional factors for 'healthy' longevity. AB - The far-reaching effects of the ageing of populations is being increasingly appreciated. Lengthening longevity, associated with decreasing family size, evokes rising charges, socioeconomically, and on health services. Information on these and other parameters is presented for developed and developing populations. Examples are given, with lessons to be learned, of long-living segments of populations, past and present. The roles of diet, physical activity, and smoking and alcohol consumption also of attitudes, are discussed. It is concluded that if the middle-aged and elderly could be persuaded to follow long-term practices associated with good public health, then morbidity could be compressed, and disability-free years extended. However, this goal could only be achieved with a high level of motivation. PMID- 8478896 TI - The research challenge for the Professions Allied to Medicine. AB - The transfer of health care schools into Higher Education, coupled with the universal development of degree programmes has resulted in the need to develop research strategies for the Professions Allied to Medicine (PAMs). While considerable reliance has to be placed on the University sector to lead and encourage research activity, it is essential to recognise the need to maintain and develop links with clinical colleagues and to promote the growth of interdisciplinary research. A variety of areas which could allow early fruition of collaborative work between the professions are proposed. PMID- 8478897 TI - Nurses ... bridging the gap: Australian aboriginals and primary health care. AB - This paper outlines a clinical learning experience designed to provide nursing students with experience in working with the Australian Aboriginal people. It also provided an opportunity for the concepts of primary health care from the rural perspective to be observed and experienced. Walgett is 433 miles or 694 kilometers from Sydney and situated in the north west of the state of New South Wales (NSW). Australia, being a large continent of some 7,682,300 square kilometers or 2,966,153 square miles, is divided into 7 states, of which New South Wales is the most populated (National Geographic Atlas of the World, 1981). PMID- 8478898 TI - Cigarette smoking and health: a radical view. PMID- 8478899 TI - The NHS: past, present and future. PMID- 8478900 TI - Mechanistic interpretation of the genotoxicity of nitrofurans (antibacterial agents) using quantitative structure-activity relationships and comparative molecular field analysis. AB - Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37. The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0.76I5,6 - 3.76; n = 40, r = 0.900, s = 0.475. The QSAR model clearly reveals three important factors, namely, electronic (qc2), hydrophobic (log P) and steric (MR, Isat, I5,6) contributing toward the genotoxic activity of this class of compounds. qc2, the charge on the c2 atom attached to the NO2 group, supports a furan ring opening mechanism in explaining the genotoxicity. The finding of the coefficient of 1 with log P conforms to our previous findings with several different classes of mutagens acting on different systems. CoMFA analysis clearly demonstrates its potential in unraveling the steric features of the molecules through contour maps. The CoMFA cross-validated model also supports the importance of the electronic factor. It could not reveal any hydrophobic influence because the interaction energies of the CH3 and H2O probes are collinear. QSAR (classical) and CoMFA, if used judiciously, may complement each other and enhance the applicability of SAR in drug design. PMID- 8478901 TI - Interaction of calcium channel antagonists with calcium: structural studies on verapamil and its Ca2+ complex. AB - The conformation of the calcium channel antagonist verapamil has been determined in acetonitrile, in the absence and presence of Ca2+, using two-dimensional 1H NMR and molecular modeling techniques. Interproton connectivities in the drug molecule were identified from the observed NOESY cross peaks and interproton distances were estimated from the magnitudes of the volume integrals of the cross peaks. The molecular modeling program utilized the Monte Carlo simulation to generate a random ensemble of conformers complying with the NOESY-derived distance constraints. The energies of these conformers were subsequently computed. The minimum-energy structure of the free drug obtained in this manner exhibited some significant differences from the structure of verapamil determined by X-ray crystallography. In particular, the torsional angles in the middle region of the molecule containing the aliphatic "backbone" were such that the two aromatic rings at either end of the drug molecules were moved farther apart from each other in solution than in the crystal structure. The nearly perpendicular orientation of the aromatic rings seen in the crystal was, however, maintained in the solution structure as well. The addition of Ca2+ to a solution of verapamil in acetonitrile caused marked changes in the difference absorbance of the drug in the 200-300-nm region and in many of its 1H-NMR resonances. The changes were most significant up to a mole ratio of about 0.5 Ca2+:drug. Analysis of the binding data at 25 degrees C showed the presence of both 2:1 and 1:1 drug:Ca2+ complexes in equilibrium, the former "sandwich" complex being dominant at the lower cation concentrations with an estimated dissociation constant of about 300 microM. All of the NOESY cross peaks of the free drug remained on addition of 0.5 mol ratio of Ca2+ to verapamil in deuterated acetonitrile and only two new connectivities were observed. Using the interproton distances calculated from these NOESY data, molecular modeling of the 2:1 drug:Ca2+ complex was carried out to yield the minimum-energy conformer. In this conformer, Ca2+ was coordinated to two methoxy oxygens from each of the two drug molecules. The implications of the verapamil Ca2+ interaction are discussed in terms of available experimental data on the binding of verapamil to the dihydropyridine-sensitive channel and in terms of a hypothesis on the formation of a drug-Ca(2+)-receptor complex in the lipid bilayer environment. PMID- 8478902 TI - Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase. AB - In an effort to develop potent human purine nucleoside phosphorylase (PNP) inhibitors as immunosuppressive and chemotherapeutic agents, several 8 aminoguanine derivatives were synthesized and evaluated as potential PNP inhibitors. These studies were designed to investigate the hydrophobic effect of a substituent on the N-9 of the purine heterocycle and/or the C-5' positions. Compounds such as 8-aminoguanosine, guanosine, formycin B, and 8-aminoacyclovir containing a p-(fluorosulfonyl)benzoyl moiety were synthesized. The affinity of these compounds to erythrocytic PNP was determined and none of these compounds showed a better affinity than those of the parent compounds. However, we found that the effect of hydrophobicity at the N-9 and the C-5' positions might play an important role in binding to the active site of PNP. Thus, 8-amino-5'-deoxy-5' (phenylthio)guanosine (19) was found to be the best inhibitor in this series of compounds with a Ki = 0.45 microM. PMID- 8478903 TI - Dicarboxylate diamide dimercaptide (N2S2) technetium-99m complexes: synthesis and biological evaluation as potential renal radiopharmaceuticals. AB - Novel diamide dimercaptide (N2S2) ligands 4, 5, and 8 have been synthesized and evaluated as potential renal radiopharmaceuticals. The target compounds were prepared in modest overall yields of 22%, 19%, and 20%, respectively, using readily available starting materials. Following in situ deprotection, 99mTc complexes of high radiochemical purity were obtained in excellent yield and were found to be stable for up to 6 h. The 99Tc complex of ligand 8 was isolated as the AsPh4 salt. The X-ray crystallographic data for [99TcO(8)]AsPh4 (space group P2(1)/n: Z = 4, a = 9.342(3) A; b = 18.594(5) A; c = 18.417(7) A; beta, deg = 90.61(3); V, A3 = 3199.1(20)) show that the Tc is bound to both thiolate sulfur atoms and to two deprotonated amide nitrogen atoms. The coordination geometry about the Tc is square-pyramidal with an -yl oxygen atom in the apical position. The Tc-N bond distances (2.002(12) and 1.984(12) A), the Tc-S bond distances (2.300(5) and 2.286(5) A), and the Tc-O bond distance (1.667(11) A) are in good agreement with bond lengths reported for similar complexes. The carboxylate groups are not bonded to the Tc atom in the solid state, nor in CDCl3 solution, as evidenced by X-ray crystal data and solution NMR data, respectively. In the solid state, [99TcO(8)]AsPh4 is monoanionic, therefore, at physiological pH, [99mTcO(8)] is presumably trianionic. Biodistribution studies performed in rats with the 99mTc complexes revealed slow blood clearance and high muscle uptake for these agents. Modest hepatobiliary excretion was observed, and low quantities of the complexes were found in the heart, lungs, and spleen after 1 h. The urinary excretion of the 99mTc complexes of ligands 4, 5, and 8 was found to be slow when compared to the excretion of [131I]OIH in rats (22%, 22%, and 32% vs 85-86%, respectively). Protein binding of 99mTc complexes of ligands 4, 5, and 8 in both rat and monkey plasma was found to be similar to MAG3. While the synthetic schemes reported here supply facile routes to novel N2S2 ligands, biodistribution studies of the 99mTc complexes performed on rats revealed slow renal excretion rates, accompanied by slow blood clearance and high uptake in muscle tissue. Preliminary planar imaging studies in monkeys also revealed slow renal excretion for these agents. The 99mTc complexes evaluated here are poor candidates as renal radiopharmaceuticals. PMID- 8478904 TI - Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT. AB - Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective anti-HIV activity in CEM cells; the magnitude of the biological effect varied considerably depending on the nature of the phosphate blocking group. Moreover, several of the compounds retain marked antiviral activity in TK- (thymidine kinase-deficient) mutant CEM cells in which AZT was virtually inactive. These data strongly support the hypothesis that the AZT phosphate derivatives exert their biological effects via intracellular release of AZT nucleotide forms and suggest that the potential of nucleoside drugs in antiviral chemotherapy may be enhanced by suitable nucleotide delivery strategies. PMID- 8478905 TI - Inhibition studies of some serine and thiol proteinases by new leupeptin analogues. AB - Fifteen tripeptide analogues of leupeptin containing either a C-terminal argininal or lysinal were synthesized. The synthetic analogues were tested, using spectrophotometric assay techniques, as inhibitors of trypsin, kallikrein, thrombin, plasmin, and cathepsin B. The lysinal analogues were fairly selective as inhibitors of cathepsin B activity. Acetyl-L-leucyl-L-valyl-L-lysinal (21) showed a stronger inhibition of cathepsin B (IC50 = 4 nanomolar) than leupeptin. Acetyl-L-phenylalanyl-L-valyl-L-argininal (2i) was found to be a good inhibitor of cathepsin B (IC50 = 0.039 microM), thrombin (IC50 = 1.8 microM), and plasmin (IC50 = 2.2 microM). PMID- 8478906 TI - Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4 oxadiazoles, and -1,2,4-triazoles as orally-active, nonulcerogenic antiinflammatory agents. AB - To discover dual inhibitors of 5-lipoxygenase (LO) and cyclooxygenase (CO) with improved pharmacokinetic properties, we have designed and synthesized series of 1,2,4-triazole, 1,3,4-oxadiazole, and 1,3,4-thiadiazole di-tert-butylphenol derivatives which exhibit a wide range of log P (2.3 to > 4) and pKa (5.5-12) values. From this work 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4 thiadiazole-2(3H)- thione, choline salt (12a, CI-986) was found to be a potent inhibitor of 5-LO (IC50 = 2.8 microM) and CO (IC50 = 0.8 microM), orally active in rat models of inflammation and nonulcerogenic. PMID- 8478907 TI - N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea hydrochloride: the first selective 5 HT1C receptor antagonist. PMID- 8478908 TI - Inhibitors of the protease from human immunodeficiency virus: synthesis, enzyme inhibition, and antiviral activity of a series of compounds containing the dihydroxyethylene transition-state isostere. AB - A number of potential HIV protease inhibitory peptides that contain the dihydroxyethylene isostere were prepared and evaluated for their enzyme binding affinity and antiviral activity in cell cultures. From the template of a previously reported active peptide A, modifications at the N- and C-terminal groups were assessed for potential maintenance of good inhibitory activity of the resulting peptides. Among the active peptides found, peptide XVIII exhibited potent enzyme inhibitory activity. Interestingly, the previously reported, effective 1(S)-amino-2(R)-hydroxyindan C-terminal group for the preparation of very active HIV protease inhibitory peptides could not be applied to the template of peptide XVIII. Molecular modeling of peptide XVIII was studied using the X-ray crystal structure of peptide A as a starting point in order to study the likely conformation of peptide XVIII in the active-site cleft. Relative binding conformations of peptide A and XVIII were obtained, although the reason for poor binding affinity for a number of congeneric peptides in this report was not straightforwardly apparent. More importantly, however, peptide XVIII was found to exhibit more effective antiviral activity in the HIV-1/PBMC assay than the reference peptide A which was previously reported to be approximately equal in efficacy to the reverse transcriptase inhibitor AZT in this assay. PMID- 8478909 TI - Binding-site modeling of the muscarinic m1 receptor: a combination of homology based and indirect approaches. AB - A model of the muscarinic m1 receptor has been constructed on the basis of the putative three-dimensional structural similarity between bacteriorhodopsin and G protein coupled receptors. The homology-based m1 receptor model takes into account hydrophobicity and conserved amino acids and information from site directed mutagenesis studies and from hydropathy plots. The resulting model was used in conjunction with an indirect model which describes a proposed active agonist conformation of acetylcholine and a number of related compounds. A receptor-excluded volume was constructed by superimposing these muscarinic agonists and calculating their combined van der Waals volume. The resulting m1 receptor excluded volume was used to define the agonist binding site, which consists of nine amino acids and which binds agonists primarily through interaction with Asp105 (ionic interaction). Thr192 and Asn382 (hydrogen bonds). The model is flexible since the conformation of the nine amino acids may change in response to the agonist structure. The combination of indirect and homology based approaches is particularly attractive since it utilizes more experimental data than a purely homology-based model and since a binding-site model might be more realistic and general in terms of applicability than indirect models. Docking of the ligands was performed by optimizing attractive interactions and minimizing repulsive interactions. In addition to the agonists used to define the binding site, structurally different agonists are also accommodated by the binding-site model. Furthermore, the m1 receptor binding-site model is able to reproduce experimentally determined stereoselectivities. PMID- 8478910 TI - Nonsymmetrical bipiperidyls as inhibitors of vesicular acetylcholine storage. AB - Introduction of a nitrogen atom into the cyclohexane ring of 2-(4 phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less potent than vesamicol. N-Benzoylation of 5 (to yield 9a) increased the potency 3-fold. In contrast, 10a, a compound derived from N-benzoylation of 6, was 50 times more potent than the latter and almost equipotent with vesamicol, thereby suggesting a preference for the 4-azavesamicol series. Although (-) vesamicol is more potent than its dextrorotary isomer, (+)-10a was found to be 3 times more potent than (-)-10a, suggesting a reversal of the sign of rotation in the azavesamicol series. Reduction of 9a and 10a (to yield the corresponding N benzyl derivatives 11a and 12a) increased potency 20- and 2-fold, respectively, indicating a preference for a basic nitrogen. The reaction of 5 or 6 with substituted benzyl halides yielded several potent inhibitors of vesicular acetylcholine transport, including N-(p-fluorobenzyl)trozamicol, 12d, which is twice as potent as vesamicol. Thus the introduction of a nitrogen atom into the cyclohexane ring of vesamicol provides opportunities for developing a new class of anticholinergic agents. PMID- 8478911 TI - Design and modeling of new platelet-activating factor antagonists. 1. Synthesis and biological activity of 1,4-bis(3',4',5'-trimethoxybenzoyl)-2-[[(substituted carbonyl and carbamoyl)oxy]methyl]piperazines. AB - To further investigate our hypothesis on the structure of the platelet-activating factor (PAF) receptor, 35 compounds derived from 1,4-bis(3',4',5' trimethoxybenzoyl)piperazine were synthesized and their in vitro antagonistic effect was measured. Substitution of the compounds in position 2, by ester or carbamate groups, giving increased steric hindrance and hydrophobicity, increased the platelet aggregation inhibitory activity from 2 microM (without substitution, compound 2) to 0.07 microM (compound 1h) and gave a maximum displacement of [3H]PAF from platelet membrane of 0.05 microM (compound 1k). It appears that the PAF antagonistic effect is only weakly enantiospecific, as observed in many cases including antagonists structurally related or not to PAF. 3D electrostatic potential maps (calculated at -10 kcal/mol) of such compounds revealed a double "Cache-oreilles" (ear-muffs) system. One of these systems has been previously described (distance between atoms generating negative wells, 11-14 A). The second shorter "Cache-oreilles" (6-7 A) system appears to be required for increased PAF antagonistic activity. This short distance between groups generating the negative wells is present in the gingkolides, a series of naturally occurring PAF antagonists. The present study indicates that the structure of the PAF receptor may be more complicated than our initial hypothesis and may be a tetrapolarized structure, with alternants of electropositive and hydrophobic areas. This modified hypothesis is in agreement with recent publications concerning PAF antagonists bearing a cationic moiety. PMID- 8478912 TI - Intercellular junctions and the application of microscopical techniques: the cardiac gap junction as a case model. AB - Intercellular junctions are fundamental to the interactions between cells. By means of these junctions, the activities of the individual cells that make up tissues are co-ordinated, enabling each tissue system to function as an integrated whole. In this review, the work of the authors on one specific type of junction--the cardiac gap junction--is presented as a case model to illustrate how the application of a range of microscopical methods, as part of a multidisciplinary approach, can help extend our understanding of cell junctions and their functions. In the heart, gap junctions form the low-resistance pathways for rapid impulse conduction and propagation, enabling synchronous stimulation of myocyte contraction. Gap junctions also form pathways for direct intercellular communication, a function of particular importance for morphogenetic signalling during development. The work discussed demonstrates some of the applications of techniques in electron microscopy, immunocytochemistry and confocal scanning laser microscopy to the understanding of the structural basis of the function of gap junctions in the normal adult heart, the developing heart and the diseased heart. Freeze-fracture electron microscopy of heart tissue prepared by rapid freezing techniques, in which excision-related structural damage to the cells is minimized or avoided, makes it possible to deduce the structure of the functioning gap junction in vivo. Gap junctions in hearts that are beating normally in the living animal until the very instant of freezing consist of connexons (transmembrane channels) organized in a quasi-crystalline arrangement, not a 'random' arrangement as proposed in the original hypothesis on the structural correlates of gap junction function. Alterations in connexon arrangement occur in response to ischaemia and hypoxia, though the relationship of these to gap-junctional permeability is indirect. To obtain probes for mapping the distribution of gap junctions in cardiac tissue, polyclonal antisera to synthetic peptides matching portions of the sequence of connexin43, the major gap junctional protein reported in the heart, were raised. The specificity of the antisera was confirmed by dot blotting, Western blotting and by immunogold labelling of isolated gap junctions. One antiserum (that raised to residues 131 142) was found to be particularly effective as a cytochemical probe. An immunofluorescence labelling procedure for use with confocal scanning laser microscopy was developed to enable the three-dimensional precision mapping of gap junctions through thick slices of cardiac tissue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478913 TI - Three-dimensional distribution of damaged cells in cryopreserved pancreatic islets as determined by laser scanning confocal microscopy. AB - The technique of serial optical sectioning by confocal microscopy, in conjunction with off-line digital image analysis, was used to quantify the radial distribution of damaged cells in rat pancreatic islets following cryopreservation. The process consists of imaging frozen-thawed islets of Langerhans using laser scanning confocal microscopy (LSCM). The three-dimensional (3-D) distribution and analysis of the two populations of viable and damaged cells was visualized via acridine orange/propidium iodide (AO/PI) fluorescent staining. In preparation for cryopreservation, isolated and cultured rat pancreatic islets were brought to a 2 M concentration of dimethyl sulphoxide (DMSO) by serial addition at decreasing temperatures. Ice was nucleated in the islet suspension at -10 degrees C, and individual specimens were frozen to -70 degrees C at cooling rates of 1, 3, 10 and 30 degrees C/min in a programmable bulk freezer and subsequently stored in liquid nitrogen. After rapid thawing and serial dilution to remove DMSO, individual islets were prepared with AO/PI stains for imaging on the LSCM. Serial sections of the islets, 2-7 microns in thickness, were obtained and processed to obtain high-contrast images. Analysis algorithms consisted of template masking, grey-level thresholding, median filtering and 3-D blob colouring. The radial distribution of damaged cells in the islets was determined by isolating the cell and computing its distance from the centroid of the 3-D islet volume. An increase in the number of blobs corresponding to single and/or aggregates of damaged cells was observed progressively with distance from the centre towards the periphery of the islet. This pattern of freeze-induced killing of cells within the islet was found to occur consistently in the numerous individual specimens processed. PMID- 8478914 TI - Modelling of three-dimensional fluorescence images of muscle fibres: an application of the three-dimensional optical transfer function. AB - Striated muscle fibres can be modelled by a simple geometry, which has allowed three-dimensional (3-D) images in conventional and confocal microscopes to be calculated. This model is useful for comparing different imaging methods and represents a simple example of an application of the 3-D optical transfer function (OTF) for the system. The rejection of out-of-focus blur is demonstrated, and the effects of fibre thickness and confocal pinhole size on image contrast are investigated. The effects of using a simple filter for image enhancement are studied, elucidating the characteristics of the OTF. PMID- 8478915 TI - Iterative, constrained 3-D image reconstruction of transmitted light bright-field micrographs based on maximum likelihood estimation. AB - We present several image reconstruction algorithms for generating three dimensional (3-D) renderings of bright-field micrographs that are founded on maximum likelihood estimation (MLE) theory. The basic principle of the algorithms is in estimating the values of the optical densities of the specimen. A computer simulation and initial experimental testing of a steepest ascent version of the algorithm is presented. The computer simulation demonstrates that the MLE algorithm has an advantage over previously used inverse filtering techniques in that it partially restores the zeroed Fourier components in the well-known missing-cone region. We present 3-D reconstructions from real biological data to show the potential of the algorithm in practical applications. PMID- 8478916 TI - Complement-stabilized D-loop. RecA-catalyzed stable pairing of linear DNA molecules at internal sites. AB - The RecA protein (RecA) of Escherichia coli has the ability to pair a single stranded DNA to a homologous sequence in a duplex DNA without requiring denaturation of the duplex. This ability has stimulated interest in the use of RecA for targeting probes to genomic DNA. However, because pairing generally requires that the double-stranded DNA either have a homologous end or be negatively supercoiled, the application of RecA to targeting has been very limited. Here, we show that if the sequence complementary to the probe is also included in the reaction, RecA can pair the two single strands to sites distant from any ends on linear DNA. The resulting structure, termed a complement stabilized D-loop (csD-loop), is cleavable by restriction endonucleases and, upon removal of RecA, remains stable to temperatures up to the tm of the double stranded probe. These results indicate that the csD-loop probably consists of two side-by-side Watson-Crick duplexes, much like a replication bubble. This novel reaction of RecA may be useful in gene mapping and isolation, as well as in sequence-specific cleavage of genomic DNA, and might have functions in vivo. PMID- 8478917 TI - Sequence-dependent DNA structure. The role of base stacking interactions. AB - The sequence-dependent structure of DNA is analysed on the basis of the energetics of the base stacking (pi-pi) interactions. The conformational preferences of the ten possible base-pair steps in double-helical DNA have been calculated and compared with experimental data from X-ray fibre diffraction, X ray crystal structures and gel-running experiments. The calculations account for many features of sequence-dependent DNA structure, including polymorphism in DNA, the lack of polymorphism in RNA, the structure of Z-DNA, bistability in pyrimidine-purine (YR) steps, the origin of propeller twist and buckle and the role of TATA sequences at the sites of origin of replication. The computational model used specifically allows for the charge distribution associated with the out-of-plane pi-electron density of the bases. The results obtained are rationalized on the basis of the shapes and charge distributions of the bases. Calladine's cross-strand steric clashes at pyrimidine-purine (YR) and CX/XG steps are reproduced. In AX/XT steps, same-strand steric clashes occur between the thymine methyl group and the 5'-neighbouring sugar. They are the cause of the large negative propeller twist observed in A.T base-pairs. Steric clashes between the thymine methyl group and the 5'-neighbouring base block A-DNA conformations in AX/XT steps. Electrostatic interactions between partial atomic charges are most important for C.G base-pairs which are highly polarized. They lead to strong preferences for positive slide and negative slide conformations in CG and GC steps, respectively. This combination can be accommodated in poly(CG) by left handed Z-DNA. Many of the more subtle sequence-dependent effects are caused by electrostatic interactions between the partial atomic charges on one base-pair and the out-of-plane pi-electron density on another. The effect is most important in CX-XG steps and leads to bistability. In general, electrostatic interactions cause non-zero slide. This is opposed by the hydrophobic effect which favours the zero slide B-type conformation. Thus, B-DNA is observed at high water content in fibres and electrostatic interactions force high or low slide A or C-DNA conformations at low water content. If two juxtaposed steps have very different conformational preferences, this incompatibility can lead to unusual structures such as Z-DNA or strain such as in TATA sequences. PMID- 8478918 TI - Molecular basis for methoxyamine-initiated mutagenesis: 1H nuclear magnetic resonance studies of oligonucleotide duplexes containing base-modified cytosine residues. AB - Methoxyamine, N4-methoxycytidine and its 2'-deoxyribo analogue are transition mutagens. The mechanism by which the latter acts after incorporation into or generation within DNA has been ascribed to the ability of the base analogue to pair effectively with both adenine and guanine. To obtain a detailed understanding of these interactions, the solution structures of the self complementary octanucleotide d(CGGATCCG) and its analogues d(CGGATTCG), d(CGGATMCG) and d(CGGATPCG) (designated 8mer-GC, -GT, -GM and -GP, respectively) were investigated by 1H nuclear magnetic resonance spectroscopy; M is N4 methoxycytosine (mo4C) and P is an analogue, the bicyclic dihydropyrimido[4,5 c][1,2] oxazin-7-one. A variable temperature study showed the order of stability as 8mer GC > GP > GT > GM. Nuclear Overhauser spectroscopy permitted the assignment of the base, anomeric and H2'/H2" protons in these 8mers. All had spectra consistent with regular B-DNA duplex structures. Imino proton spectra showed that the 8mers GC, GP and GM involved Watson-Crick base-pairing but that the G.P and to a greater extent G.M base-pairs were in slow exchange on the nuclear magnetic resonance time-scale with the wobble configuration. Indeed, the G.M pair showed an additional exchange process interpreted in terms of the presence of syn and anti conformers of the methoxy group in the wobble pair. This accounts for the destabilization of M compared with the P-containing duplex. The observations are compared with those made earlier on the corresponding AT, AP and AM octamers. It is evident that M and P can form stable base-pairs with both A and G with essentially Watson-Crick geometry. This confirms the earlier, although unsubstantiated explanation for the transition mutational propenstty of methoxyamine which, in turn, was based on the fact that methoxycytosine bases have tautomeric constants (KT) much nearer to unity than the normal bases. The same general explanation for hydroxylamine and hydrazine-induced mutations is correspondingly rendered more certain. PMID- 8478919 TI - Crystallization and stoichiometry of binding of a complex between a rat intestinal Fc receptor and Fc. AB - Fc receptors expressed in the gut of newborn rodents bind to maternal immunoglobulin in milk at pH 6.5, and transport it to the bloodstream of the neonate, where it dissociates at pH 7.4. The rat intestinal Fc receptor (FcRn) consists of a heavy chain, with significant sequence similarity to the heavy chain of class I MHC molecules, complexed to the class I light chain, beta 2 microglobulin. Although FcRn is predicted to contain a groove analogous to that which serves as the MHC peptide-binding site, the immunoglobulin ligand of FcRn is a macromolecule instead of a peptide. We have expressed and crystallized a secreted form of FcRn, and here report the crystallization of a complex between FcRn and its Fc ligand. Isolated FcRn-Fc complexes crystallize in space group I222 or I2(1)2(1)2(1) with unit cell dimensions a = 125 A, b = 152 A and c = 216 A. The crystals diffract to 5.5 A resolution with anisotropic diffraction to 3.5 A. Data collection from cryopreserved crystals may allow the resolution limit to be extended, since the major reason for the poor resolution appears to be radiation decay. Even a low-resolution view of how FcRn binds Fc would be of interest to see if the binding site corresponds to the functional part of an MHC molecule. Since the structure of Fc is known, and a structure determination of FcRn is underway, it may be possible to locate the Fc binding site on FcRn at low resolution. As an initial characterization of the FcRn-Fc mode of interaction, and to facilitate the structure determination, we have determined the stoichiometry of binding of FcRn to Fc. We show that two FcRn molecules bind per Fc, as determined by analysis of gels of washed crystals, a column binding assay, and isothermal titration calorimetry. PMID- 8478920 TI - Isolation, crystallization and preliminary diffraction analyses of human pancreatic alpha-amylase. AB - Human pancreatic alpha-amylase has been isolated using a glycogen affinity precipitation procedure and crystallized in a form suitable for high resolution three-dimensional X-ray crystallographic analyses. Crystals are of the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions of a = 53.04 A, b = 74.80 A and c = 137.34 A, and contain only one protein molecule per asymmetric unit. Diffraction data have been collected and found to extend to 1.6 A resolution. These studies form the basis for elucidating the full atomic structure of human pancreatic alpha-amylase and thereby providing insight into the catalytic mechanism of this enzyme. PMID- 8478921 TI - Crystallization and preliminary X-ray diffraction studies of a NADH oxidase from Thermus thermophilus HB8. AB - The thermophile NADH oxidase from Thermus thermophilus, cloned and expressed in Escherichia coli, has been purified to homogeneity and crystallized. Three different crystal forms were found to be suitable for X-ray diffraction analysis. Crystals of the tetragonal form, grown in the presence of 25% polyethylene glycol 4000 and 0.25 M-NaCl at pH 6.6, were chosen for further analysis. These crystals belong to the space group P4(1)(3)2(1)2 with refined lattice constants of a = 94.8 A and c = 49.0 A, indicating a cell content of one monomer per asymmetric unit of the crystal. The crystals diffract to a resolution of 2.2 A. PMID- 8478922 TI - Crystallization of Bacillus subtilis tryptophanyl-tRNA synthetase. AB - Tryptophanyl-tRNA synthetase from Bacillus subtilis was overexpressed in Escherichia coli and was purified using column chromatography on DEAE-Sephacel and hydroxyapatite columns. Single crystals of the synthetase were grown by vapor diffusion at 4 degrees C from pH 5.5 solutions of polyethylene glycol 8000 containing magnesium ATP and L-tryptophan. The crystals diffracted to about 4.0 A resolution at -150 degrees C and appeared to belong to the orthorhombic space group P2(1)2(1)2 with unit cell dimensions: a = 143.6 A, b = 111.6 A, c = 50.6 A with one dimer in the asymmetric unit. PMID- 8478923 TI - Crystallization of a deletion mutant of the R-subunit of cAMP dependent protein kinase. AB - A single deletion (delta 1 to 91) mutant of the regulatory subunit of the cAMP dependent protein kinase was crystallized. The crystals are hexagonal P6(1)22 (P6(5)22) with a = b = 88.7 A and c = 179.9 A. The crystals diffract to 3 A resolution. There is one molecule per asymmetric unit. PMID- 8478924 TI - Diffraction grade crystals of Escherichia coli serine hydroxymethyltransferase. AB - Diffraction grade crystals of serine hydroxymethyltransferase were obtained after extensive screening of source of enzyme, purification procedures, ligand binding and crystallization conditions. Serine hydroxymethyltransferase purified from Escherichia coli crystallizes in two forms that are suitable for crystal structure determination. PMID- 8478925 TI - Crystallization of DsbA, an Escherichia coli protein required for disulphide bond formation in vivo. AB - DsbA is a 21 kDa protein that facilitates disulphide bond formation and is required for the correct folding and stability of a number of exported proteins in Escherichia coli. Crystals of oxidized DsbA have been obtained from polyethylene glycol 8000 (20 to 25%), 0.1 M-cacodylate buffer (pH 6.5) and 1% 2 methyl-2,4-pentanediol. Oxidation of the protein is critical for reproducibly obtaining high quality crystals. The resulting crystals diffract to 2 A and belong to the monoclinic space group C2 with cell dimensions a = 117.5 A, b = 65.0 A, c76.3 A, beta = 126.3 degrees with two molecules in the asymmetric unit. PMID- 8478926 TI - Identification of a cis-acting sequence within the Pm promoter of the TOL plasmid which confers XylS-mediated responsiveness to substituted benzoates. AB - The DNA sequences within the Pm promoter/operator region of the meta operon of the TOL plasmid of Pseudomonas putida, which confer XylS-mediated responsiveness to substituted benzoates, have been identified through deletion analysis and mutagenesis of the region. Integrity and proper phasing of two homologous tandem sequences 5'-TGCAAPuAAPu-PyGGNTA-3', separated by six base-pairs and overlapping with the -35 region of the Pm promoter, was essential for m-toluate activation of a Pm-lacZ fusion in xylS+ strains. The spacing between equivalent bases in each of the half-sites is 21 base-pairs, i.e. two turns of DNA helix. The activity of Pm varieties containing identical half-sites suggested that the XylS-responsive element is arranged as a direct repeat, the distal sequence being the one which provided the most stringent regulation when duplicated. The role of the repeats as the target for XylS binding to Pm is discussed. PMID- 8478927 TI - Expression of bacteriophage T4 gene 25 is regulated via RNA secondary structure in the translational initiation region. AB - Analysis of the nucleotide sequence in the 5' flanking region of bacteriophage T4 gene 25 revealed three potential Shine and Dalgarno sequences, SD1, SD2 and SD3, with a spacing of 8, 17 and 27 nucleotides from the initiation codon of this gene, respectively. Results of our experiments in the bacteriophage T7 expression system clearly demonstrate that the SD3 sequence is required for efficient expression of gene 25. We propose the existence of a stem-loop structure that includes SD1 and SD2 sequences and brings the SD3 sequence to a favourable spacing with the initiation codon of gene 25. Since the predicted secondary structure in the translational initiation region of gene 25 is relatively unstable and the SD3 sequence, GAGG, is more typical than the SD1 sequence, GAG, we suggest that this structure could control the level of gene expression. PMID- 8478928 TI - Re-refinement of the X-ray crystal structure of bovine lens leucine aminopeptidase complexed with bestatin. AB - Bestatin, (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine, has been incorrectly modelled in the previously reported structure of the complex between bovine lens leucine aminopeptidase (blLAP) and bestatin. In the previously reported structure, the C2 of bestatin was modelled and refined in the R configuration instead of the correct S configuration. The structure of the blLAP bestatin complex has been re-refined after remodelling bestatin in its correct stereochemistry. PMID- 8478929 TI - Functional expression of the uncomplexed serum retinol-binding protein in Escherichia coli. Ligand binding and reversible unfolding characteristics. AB - The serum retinol-binding protein solubilizes the lipophilic vitamin A alcohol and plays an important physiological role in the transport of this compound. The monomeric single-domain protein, the three-dimensional structure of which is known, constitutes a well-characterized member of the lipocalin family of proteins. We report here the functional expression of the apo-protein in Escherichia coli by secretion to the periplasm. The recombinant protein, purified in a single step by metal chelate affinity chromatography, exhibits the same ligand binding characteristics as described for the natural protein. Guanidinium chloride-induced unfolding and refolding experiments suggest that the recombinant retinol-binding protein adopts a stable conformation despite being expressed and purified in the absence of the large hydrophobic ligand. The expression system described here should also be useful for the recombinant production of other lipocalin proteins, thus permitting the elucidation of the structure-function relationships of ligand binding by protein engineering. PMID- 8478930 TI - Double strand packing in hemoglobin S fibers. AB - The sickling variant of human hemoglobin, Hb S (beta 6 Glu-->Val), assembles into 14-strand helical fibers composed of seven pairs of double strands. The organization of the helical double strands closely resembles the parallel, half staggered, linear strand pairs of the crystals of Hb S characterized by Wishner et al. In the crystals, the molecules are arranged such that each possesses a beta 6 Val in contact with a molecule on the opposite strand. In the fibers, the overall hexagonal packing of strands leads to 22 classes of potential contacts between the seven double strands, but the presence of 2-fold helical symmetry reduces these contacts to 11 distinct classes. An analysis of the intermolecular contacts reported by Watowich et al., based on the data of Carragher et al., indicated a loosely packed structure for which only four of the 11 potential classes of contacts between double strands are significant (residues within 5 A). We have recently analyzed the packing based on the results of Dykes et al. and Rodgers et al., and compared the findings with the structure derived from the data of Carragher et al. We find serious differences between the two data sets concerning the packing of double strands. The Dykes-Rodgers data indicate a more closely packed structure in which nine of the 11 potential classes of contacts are within 5 A. Considerations on the stability of certain contacts derived from incomplete fibers, as well as studies of Hb molecules composed of beta S chains and mutant alpha chains, suggest that the structural model with closer packing of the double strands provides a better correlation with the other experimental results. PMID- 8478931 TI - Undiscriminating codon reading with adenosine in the wobble position. AB - To investigate the reading properties of adenosine in the wobble position we have used site-directed mutagenesis of the Escherichia coli glycine tRNA1(CCC) gene to substitute the nucleotide A in the wobble position of the corresponding tRNA. The effect of this change on the ability of the tRNA to discriminate between the nucleotides in the third position of the glycine codons has been investigated. We have compared the ability of the mutant glycine tRNA1(UCC) and glycine tRNA1(ACC) as well as the mycoplasma glycine tRNA(UCC) to read the glycine codons. The results showed that glycine tRNA1(ACC) unlike glycine tRNA1(UCC) did not fully discriminate between the glycine codons. These experiments were carried out using a new in vitro protein synthesizing system that allows us to monitor the reading of all four glycine codons. In the present paper we give a detailed description of this new in vitro system. PMID- 8478932 TI - Conformation and thermodynamics of DNA "necks". Models for three-arm branch formation in a duplex. AB - The properties of three-arm DNA junctions differ from those of four-arm junctions in several respects. Most apparently, bases flanking the branch are reactive to single strand specific agents in three-arm junctions but not four-arm junctions. To determine the basis for this, we have designed and synthesized a series of complexes in which a short duplex, a neck, progressively extends from a parent 16 mer DNA duplex. These structure allow us to investigate how a three-arm branch forms, and how its properties change as the neck extends. Comparison of the properties of a nicked duplex with those of the neck structures using native gel electrophoresis with reporter arms attached reveals progressively greater geometrical perturbation of the complexes as the number of base-pairs in the neck increases. Footprinting by single-strand specific reagents indicates that the reactivity to single-strand reagents near the branch occurs when only a single pair is possible. The branch in each neck interacts tightly with ethidium, as does a nick in the same duplex. The thermodynamics of neck formation have been evaluated by calorimetry and from the concentration dependence of absorbance temperature profiles. Each neck complex is destabilized with respect to duplex DNA or a nicked duplex, and has a lower enthalpy of formation despite the increased number of base-pairs present. A model is proposed to account for these properties in which the bases in the pair adjacent to the duplex interact directly with the duplex, via transient insertion. PMID- 8478933 TI - Effects of co-factor and deoxycytidine substituted oligonucleotides upon sequence specific interactions between MspI DNA methyltransferase and DNA. AB - MspI methyltransferase (M.MspI) catalyses the transfer of a methyl group from S adenosyl-L-methionine to the C-5 position of the outer deoxycytidine base in the DNA sequence 5'-CCGG-3'. Recombinant M.MspI when expressed and purified as a translational fusion with glutathione-S-transferase, shows all of the properties of the wild-type enzyme. We report the kinetic analysis of M.MspI binding to DNA, which suggests a two-stage methylation process, whose initial DNA binding rate is governed by the presence of a positively charged sulphonium centre on the cofactor. Results are also presented that indicate that M.MspI binds preferentially to hemi-methylated DNA and that full methylation of either deoxycytidine on both strands significantly impairs sequence-specific protein-DNA interactions. Furthermore, the importance of the 4-amino group of the inner deoxycytidine for sequence-specific protein-DNA interactions is demonstrated by substituting deoxycytidine with 2-pyrimidinone-1-beta-D-2-deoxyriboside. In addition, we detail the intrinsic structural elements of a cofactor, required to enhance the binding of M.MspI to its recognition sequence, by using S-adenosyl-L methionine and a range of derivatives. PMID- 8478934 TI - Structure of the sequences adjacent to the centromeric alphoid satellite DNA array on the human Y chromosome. AB - Eighteen yeast artificial chromosome (YAC) clones containing alphoid satellite DNA and adjacent sequences from the human Y chromosome have been identified from three different YAC libraries. Restriction site mapping of the genomic alphoid arrays and the YACs has allowed seven of the alphoid clones to be positioned on the arrays. Three clones extend into flanking sequences. At one edge the alphoid DNA is highly diverged and is flanked by a small block of the 48 base-pair satellite, dispersed moderately repeated sequences and a separate short alphoid array. More distal sequences are Y-specific. At the other edge there is much less divergence and the alphoid DNA is flanked by an Alu sequence and the five base pair satellite. PMID- 8478935 TI - Structure of the maltodextrin-uptake locus of Streptococcus pneumoniae. Correlation to the Escherichia coli maltose regulon. AB - The mechanism of induction of the maltose/maltodextrin regulon of the Gram positive bacterium Streptococcus pneumoniae seems to be different to the positively controlled maltose regulons of the enteric bacteria Escherichia coli, Klebsiella pneumoniae and Salmonella typhimurium. In this work, we report on the structure of the S. pneumoniae genes involved in maltodextrin uptake malX, malC and malD. Comparisons of the amino acid sequences encoded by these genes indicate that they are homologous to the E. coli MalE periplasmic maltose binding protein and the two maltose permeases MalG and MalF. The analysis of transcription start points indicates that malXCD could be transcribed from a single consensus promoter sequence. Northern analysis of the mRNA molecules pertaining to this region reveals that the transcript encompassing all these three genes is apparently cleaved at a large putative mRNA secondary structure, yielding two mRNA molecules. The smaller of these molecules would include only the malX gene while a larger fragment spans through malC and malD. The processing of mRNA has not been reported in the Gram-negative maltose regulons, and may suggest either a less evolved or a divergent system for the control of gene expression of this regulon in S. pneumoniae. PMID- 8478936 TI - Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. AB - A large number (33) of human Fab fragments reacting with HIV-1 surface glycoprotein gp120 have been generated by selection from a combinatorial IgG1 kappa library displayed on the surface of phage. The library was prepared from a long term asymptomatic HIV-seropositive donor. Analysis of the sequences from these Fabs shows the heavy chains can be placed in groups, many of which contain intraclonal variants, almost certainly corresponding to chains used in vivo. Further variants can be accessed via chain shuffling experiments in which a given light chain is recombined with a library of heavy chains. Heavy chain promiscuity, i.e. the ability of heavy chains to pair with different light chains with retention of antigen binding, is dependent on the particular heavy chain considered and probably excludes the identification of in vivo light chain partners. The antibodies examined here are primarily to the CD4 binding site on gp120 and broadly reflect the serum profile of the donor. The antibodies show evidence of extensive somatic modification indicative of an antigen-driven response. The heavy chain CDR3 regions of the antibodies show a remarkably conserved extended length. A number also show strong sequence conservation in CDR3 against a background of considerable diversity in the rest of the VH gene supporting a central role for this region in antigen recognition. PMID- 8478937 TI - Reconstitution of short-spaced chromatin from the histone octamer and either HMG 14,17 or histone H1. AB - Two new chromatin-assembly reactions are described. The first involves the addition of phosphorylated HMG-14,17 to the histone octamer plus DNA in high concentrations of salt and yields a repeating particle size or spacing of about 165 base-pairs. The second involves the addition of histone H1 to the acetylated histone octamer plus poly(glutamate) in low concentrations of salt, followed by the addition of DNA; and it yields a spacing of about 170 base-pairs. Plots of band size versus band number in gels, often used to determine nucleosome repeat length, yield slopes of 138 base-pairs for the histone octamer alone, or 155 base pairs with HMG-14,17 or 160 base-pairs with histone H1, and intercepts of 10,25 and 20 base-pairs, respectively, in the three cases. Attempts were made to combine the spacing activities of HMG-14,17 and histone H1 within a single assembly reaction, to provide an even longer spacing of about 190 base-pairs (as observed in cell extracts to which H1 has been added), but our present methods did not allow this. The two assembly reactions described here will be of use for structural studies of chromatin having defined length and sequence, and potentially of practical use for the regular, ordered condensation of very long DNA. PMID- 8478938 TI - Separation and characterization of homo and hetero-oligomers of the intermediate filament proteins desmin and vimentin. AB - Affinity chromatography on single-stranded (ss)DNA-cellulose in conjunction with gel permeation chromatography in the presence of urea was employed to separate the intermediate filament (IF) protein complement of catalytically oxidized BHK 21 cell Triton cytoskeletons into disulfide-cross-linked homo- and heterodimers of desmin and vimentin and uncross-linked homodimers. The same separation was performed on a desmin-vimentin mixture under autoxidizing conditions in 6 M-urea to obtain the respective cross-linked collision complexes of both proteins. In 5 M-urea, the oxidation products were identified as dimers that were physically indistinguishable from uncross-linked homodimers, suggesting that they were in the form of partially denatured face-to face pairs. Heterodimers derived from intact IFs were identical to those derived from collision complexes. In the presence of 2-mercaptoethanol, heterodimers were unstable and transformed spontaneously into homodimers. After removal of urea, all cross-linked dimers were totally unable to polymerize into filaments; however, in the presence of 2 mercaptoethanol they showed a normal assembly competence. This inability of oxidized homo- and heterodimers to polymerize, together with the relatively low yield of cross-linked dimers obtained from cytoskeletons, is probably due to the introduction of steric strain into the dimers by disulfide bond formation. Substantial amounts of cross-linked heterodimers could also be isolated from IFs reconstituted from mixtures of desmin and vimentin in their homodimeric or tetrameric forms. Taken together, these results suggest that the cross-linked dimers isolated from cytoskeletons arise from a reaction between subfilament strands of IFs rather than from disulfide bond formation within pre-existing dimers and that the heterotypic IFs of BHK-21 cells are largely formed from homodimers and tetramers, respectively, rather than from heterodimers. The differential capacity of desmin and vimentin to interact with ssDNA has also been exploited to distinguish between homotypic and heterotypic protofilaments, the latter consisting of one homodimer of each protein species. This distinction could be made on the basis of characteristic differences in the sedimentation behavior of the respective protein-DNA complexes. PMID- 8478939 TI - Endonuclease VII of phage T4 triggers mismatch correction in vitro. AB - The reactivity of endonuclease VII (gp49 of phage T4) with DNA-loops of eight, four, or one nucleotide, or any of 12 possible base mismatches was tested in vitro. Endonuclease VII introduces double-strand breaks by nick and counter-nick within six nucleotides 3' from the mispairings. High relative cleavage efficiencies at mismatches in heteroduplexes correlate with their decreased thermal stability and vice versa. A delay between nick and counter-nick was sufficient to allow T4 DNA-polymerase and T4 DNA-ligase to correct a C/C-mismatch in vitro, thereby saving the DNA from double-strand breakage. Very short repair tracks of three to four nucleotides mapped between the mismatch and one of the formerly induced nicks, which were subsequently sealed by DNA ligase. PMID- 8478940 TI - Interactions between morpholinyl anthracyclines and DNA. The crystal structure of a morpholino doxorubicin bound to d(CGTACG). AB - Anthracycline antibiotics daunomycin and adriamycin are among the most widely used in cancer chemotherapy and DNA is believed to be the primary target of their biological action. The crystal structure of a morpholino derivative of adriamycin bound to the DNA hexamer d(CGTACG) has been determined at 1.5 A resolution. The complex crystallizes in space group P1 with unit cell dimensions a = 18.01 A, b = 18.83 A, c = 27.65 A, alpha = 92.6 degrees, beta = 100.5 degrees, gamma = 94.9 degrees and there are two drug molecules bound per duplex. Morpholino derivatives differ greatly from their parent compounds in their biological and pharmacological properties. Structural comparison of this complex with the series of previously reported anthracycline-DNA complexes offers an opportunity for studying relationships between structure and function. The anthracycline chromophore intercalates at the CpG step and DNA distortions from a B-type conformation are similar to those observed in the other DNA-anthracycline complexes. Interactions between drug and DNA show no differences at the intercalation site, while in the minor groove they are significantly affected by the presence of the bulky morpholinyl moiety on the anthracycline amino sugar. The binding site involves four base-pairs and the absence of a positive charge on the amino sugar appears to influence the hydration pattern on both grooves. The two halves of the duplex are symmetrically related by a non-crystallographic 2 fold axis but they are not equivalent. In one half, one magnesium cluster bridges both drug and DNA, further stabilizing the complex. PMID- 8478941 TI - Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. AB - Heat-labile enterotoxin (LT) from Escherichia coli is a bacterial protein toxin with an AB5 multimer structure, in which the B pentamer has a membrane binding function and the A subunit is needed for enzymatic activity. The LT crystal structure has been solved using a combination of multiple isomorphous replacement, fivefold averaging and molecular dynamics refinement. Phase combination using all these sources of phase information was of crucial importance for the chain tracing. The structure has now been refined to 1.95 A resolution, resulting in a model containing 6035 protein atoms and 293 solvent molecules with a crystallographic R-factor of 18.2% and good stereochemistry. The B subunits are arranged as a highly stable pentamer with a donut shape. Each subunit takes part in approximately 30 inter-subunit hydrogen bonds and six salt bridges with its two neighbors, whilst burying a large surface area. The A subunit has higher temperature factors and less well-defined secondary structure than the B subunits. It interacts with the B pentamer mainly via the C-terminal A2 fragment, which runs through the highly charged central pore of the B subunits. The pore contains at least 66 water molecules, which fill the space left by the A2 fragment. A detailed analysis of the contacts between A and B subunits showed that most specific contacts occur at the entrance of the central pore of the B pentamer, while the contacts within the pore are mainly hydrophobic and water mediated, with the exception of two salt bridges. Only a few contacts exist between the A1 fragment and the B pentamer, showing that the A2 fragment functions as a "linker" of the A and B parts of the protein. Interacting with the A subunit by the B subunits does not cause large deviations from a common B subunit structure, and the 5-fold symmetry is well maintained. A potential NAD(+) binding site is located in an elongated crevice at the interface of two small sheets in the A1 fragment. At the back of this crevice the functionally important Arg7 makes a hydrogen bond connecting two strands, which seems to be conserved across the ADP-ribosylating toxin family. The putative catalytic residue (A1:Glu112) is located nearby, close to a very hydrophobic region, which packs two loops together. This hydrophobic region may be important for catalysis and membrane translocation. PMID- 8478942 TI - Relocating a negative charge in the binding pocket of trypsin. AB - The functional and structural consequences of altering the position of the negatively charged aspartate residue at the base of the specificity pocket of trypsin have been examined by site-directed mutagenesis, kinetic characterization and crystallographic analysis. Anionic rat trypsin D189G/G226D exhibits a high level of catalytic activity on activated amide substrates, but its relative preference for lysine versus arginine as the P1 site residue is shifted by 30 to 40-fold in favor of lysine. The crystal structure of this variant has been determined in complexes with BPTI (bovine pancreatic trypsin inhibitor), APPI (amyloid beta-protein precursor inhibitor domain) and benzamidine inhibitors, at resolutions of 2.1 A, 2.5 A and 2.2 A, respectively. Asp226 bridges the base of the specificity pocket with its negative charge partially buried by interactions made with Ser190 and Tyr228. An equal reduction in the affinity of the variant enzyme for Arg and Lys substrates is attributable to a decreased electrostatic interaction of each ligand with the relocated aspartate residue. Comparison of structural and functional parameters with those of wild-type trypsin suggests that direct hydrogen-bonding electrostatic contacts in the S1 site do not significantly improve the free energy of substrate binding relative to indirect water-mediated interactions. The conformation adopted by Asp226, as well as by other adjacent side-chain and backbone groups, depends upon the ligand bound in the primary specificity pocket. This structural flexibility may be of critical importance to the retention of catalytic activity by the variant enzyme. PMID- 8478943 TI - Structures of the lectin IV of Griffonia simplicifolia and its complex with the Lewis b human blood group determinant at 2.0 A resolution. AB - The structures of the fourth lectin isolated from Griffonia simplicifolia (GS4) and its complex with the methyl-glycoside of the Lewis b human blood group determinant (Le(b)-OMe) are reported at high resolution. The native GS4 crystal is isomorphous with the complexed GS4 crystal. The space group is P4(2)2(1)2 with unit cell dimensions a = 78.9 A, c = 89.1 A with one subunit of the lectin (bound to 1 Le(b)-OMe in the complex) in the crystallographic asymmetric unit. The native GS4 structure was solved by the molecular replacement technique and least squares refined (PROLSQ and X-PLOR). The orientation of the Le(b)-OMe tetrasaccharide in the complex was established from a 2.8 A difference map with coefficients (Fcomplex--Fnative) and calculated phase angles from the native model. Both the final native and complex GS4 models consist of 1904 protein non hydrogen atoms, one sulfate ion, one Ca ion, one Mn ion and three covalently bound sugar residues N-linked to Asn18. In addition, the complex model has 47 Le(b)-OMe non-hydrogen atoms. The two structures have 135 water molecules in common in addition to eight and nine unique water molecules in the native and complex structures, respectively. The root-mean-square deviations from ideal bond distances and angles are 0.016 A, 3.2 degrees and 0.016 A, 3.0 degrees, for the native and complexed GS4, respectively. The R index for all unique data from 8 to 2.0 A is 0.187 for the native (19,204 reflections) and 0.181 for the complex (19,212 reflections). The tertiary structure of each subunit is similar to that of other leguminous lectins but the quaternary structure of the molecular dimer is different from that of any other lectin reported to date. The co-ordination about the Ca ion is pentagonal bipyramidal (with 1 long Ca(2+)-oxygen bond) and the co-ordination about the Mn ion is octahedral. Two conserved residues (Asp149 and Ser155) appear to be important because they are hydrogen-bonded to each other and to groups that co-ordinate the Mn ion. There are three cis-peptides in the polypeptide chain; two involve non-proline residues, one of which is homologous with other leguminous lectins and the other is unique to GS4. The two non-proline cis-peptides are located in the carbohydrate-binding site and are important for the specificity of the lectin. The molecular recognition of Le(b)-OMe by GS4 involves both polar and extensive non-polar interactions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478944 TI - Characterization of the zinc-induced structural transition to *H-DNA at a d(GA.CT)22 sequence. AB - Zinc induces transition of a d(GA.CT)22 sequence to a novel DNA conformation, called *H-DNA. In this paper, the structural characteristics of this altered DNA conformation are determined. Formation of *H-DNA is induced at zinc concentrations higher than 70 microM (Zn/P = 2) and it is favoured by negative supercoiling and low ionic strength. Two different structural conformations of the d(GA.CT)22 sequence are observed upon increasing the zinc concentration. At low zinc concentration (Zn/P < 15), half of the purine strand falls back upon itself giving rise to the formation of an RRY intramolecular triplex (H* triplex). At higher zinc concentration, the complete pyrimidine strand is single stranded and an RR hairpin is formed (*H-hairpin). Protection towards dimethylsulphate modification suggests that zinc binds to the N-7 group of guanine residues in the *H-hairpin with a higher affinity than in B-DNA. The dissociation constant of the *H-zinc complex is estimated to be in the range of 10(-3) M to 10(-4) M. PMID- 8478945 TI - X-ray structures and mechanistic implications of three functional derivatives of ascorbate oxidase from zucchini. Reduced, peroxide and azide forms. AB - The X-ray structures of three functional derivatives of ascorbate oxidase (EC 1.10.3.3) from Zucchini have been determined and are compared to the "native" oxidized form. The fully reduced form of ascorbate oxidase has been refined to a crystallographic R-factor of 19.6% for all reflections between 8.0 A and 2.2 A resolution. The geometry at the type-1 copper (CU1) is unchanged compared to the oxidized form, but the oxygen ligand bridging the copper ions CU2 and CU3 (spectroscopic type-3 copper pair) is released and the copper ions move apart yielding a trigonal planar co-ordination with their ligating histidine residues. The co-ordination at the copper ion CU4 (spectroscopic type-2 copper) is not affected. The copper-copper distances increase from an average 3.7 A in the native form to 5.1 A for CU2-CU3, 4.4 A for CU2-CU4 and 4.1 A for CU3-CU4. The peroxide derivative of ascorbate oxidase has been refined to a crystallographic R factor of 16.0% for all reflections between 8.0 A and 2.59 A resolution. The geometry at the type-1 copper site is not changed compared to the oxidized form. The oxygen ligand bridging copper atoms CU2 and CU3 is lost, too. The peroxide binds terminally to the copper ion CU2 as hydroperoxide. Copper ion CU2 is fourfold co-ordinated to the NE2 atoms of the three histidine residues and to the oxygen atom of the terminally bound peroxide molecule in a distorted tetrahedral geometry. Copper ion CU3 is threefold co-ordinated as in the reduced form and co ordination around copper atom CU4 is unaltered. The copper-copper distances increase to 4.8 A for CU2-CU3 and 4.5 A for CU2-CU4. The distance CU3-CU4 remains 3.7 A. Treatment with peroxide causes a partial depletion of copper ion CU2. The refinement for the azide derivative of ascorbate oxidase converged at a crystallographic R-factor of 17.8% for all reflections between 8.0 A and 2.32 A. There are no significant structural changes at the type-1 copper site. The oxygen ligand bridging copper ions CU2 and CU3 is again released. Two azide molecules bind terminally to copper ion CU2. Copper ion CU2 is fivefold co-ordinated to the NE2 atoms of the three histidine residues and to both terminally bound azide molecules in a trigonal-bipyramidal manner. Copper-copper distances increase to 5.1 A for CU2-CU3 and 4.6 A for CU2-CU4. The distance CU3-CU4 is decreased to 3.6 A.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8478946 TI - The Slezak workshop on antiarrhythmic drugs and self ventricular defibrillation. A satellite to the XIV European meeting of the International Society for Heart Research. Tel-Aviv, 6-7 May, 1993. Abstracts. PMID- 8478947 TI - International Society for Heart Research. XIV European Section Meeting. Jerusalem, Israel, May 9-13, 1993. Abstracts. PMID- 8478948 TI - Supratentorial malignant gliomas: risk patterns and therapy. PMID- 8478949 TI - Do hormones link alcohol with breast cancer? PMID- 8478950 TI - Collins takes helm of NIH genome project. PMID- 8478952 TI - Spain's cancer researchers ready for next step. PMID- 8478951 TI - Sphingolipids implicated in programmed cell death. PMID- 8478953 TI - Registries keep track in Spain. PMID- 8478954 TI - Study suggests mechanism for alcohol-breast cancer link. PMID- 8478955 TI - States aim laws at off-label reimbursement. PMID- 8478956 TI - Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. AB - BACKGROUND: Despite notable technical advances in therapy for malignant gliomas during the past decade, improved patient survival has not been clearly documented, suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy. Age, performance status, and tumor histopathology have been identified as the pretreatment variables most predictive of survival outcome. However, an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma. PURPOSE: This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration. This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials. METHODS: We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer. This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival. Twenty-six pretreatment characteristics and six treatment-related variables were analyzed. RESULTS: The years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7-58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients. CONCLUSIONS: This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis. IMPLICATIONS: The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials. PMID- 8478957 TI - Role of antioxidant enzymes in the induction of increased experimental metastasis by hydroxyurea. AB - BACKGROUND: Treatment of tumor cells with hydroxyurea and other DNA-damaging agents has been shown to increase the experimental metastatic potential of these cells. PURPOSE: We sought to elucidate some of the biochemical and genetic changes that promote tumor cell metastasis in hydroxyurea-treated cells. We hypothesized that drug treatment induces resistance to oxidative damage and that elimination of this resistance reverses the drug-induced experimental metastatic capabilities of tumor cells. METHODS: We examined the effect of hydroxyurea treatment on B16 melanoma cells with respect to experimental metastatic potential, resistance to hydrogen peroxide (H2O2), glutathione peroxidase activity and messenger RNA (mRNA) level, glutathione reductase activity, glutathione levels, glutathione-S-transferase activity, and catalase activity and mRNA level. RESULTS: Hydroxyurea-treated cells were transiently more metastatic following intravenous injection in syngeneic mice and transiently more resistant than untreated cells to exogenous H2O2. Hydroxyurea-induced experimental metastases and H2O2 resistance were eliminated by depletion of intracellular glutathione with buthionine sulfoximine. Glutathione peroxidase activity and mRNA level, glutathione reductase activity, and reduced glutathione levels were all transiently increased in hydroxyurea-treated cells, whereas the increase in glutathione-S-transferase activity was sustained. Catalase activity was modestly increased with no increase in its mRNA levels. CONCLUSIONS: In B16 melanoma cells, experimental metastasis induced by hydroxyurea appears to depend on a process that requires glutathione. Hydroxyurea treatment also induces resistance to exogenous H2O2, which may be due to induction of glutathione and antioxidant enzyme activity. IMPLICATIONS: The role of antioxidants in B16 melanoma cells offers new insights into the metastatic process and the cellular response to chemotherapy. PMID- 8478958 TI - Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women. AB - BACKGROUND: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. PURPOSE: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. METHODS: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21-40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each diet. RESULTS: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P = .05). In the peri-ovulatory phase, there were increases of 21.2% (P = .01) in plasma estrone levels, 27.5% (P = .01) in plasma estradiol levels, and 31.9% (P = .009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P = .05), estradiol levels increased 21.6% (P = .02), and estriol levels rose 29.1% (P = .03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. CONCLUSION: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women. IMPLICATION: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation. PMID- 8478959 TI - Randomized phase I chemoprevention dose-seeking study of alpha difluoromethylornithine. AB - BACKGROUND: alpha-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. Levels of ODC are closely related to tumor promotion, and inhibition of ODC is associated with suppression of tumor development in laboratory animals. DFMO has shown a dose-response effect in tumor inhibition in mice. PURPOSE: A randomized phase I study of DFMO was conducted to determine the lowest daily oral dose that can achieve at least 50% inhibition of ODC activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human skin, with minimal clinical toxicity (grade 1 or lower; Eastern Cooperative Oncology Group [ECOG]). METHODS: Cancer patients entered in steps 1 and 2 of the study had been treated and had no clinical evidence of cancer. In step 1, 13 patients received 0.125, 0.25, 0.5, or 0.75 g/m2 DFMO four times a day. In step 2, 13 patients received 0.125 or 0.25 g/m2 four times a day or 0.5 or 1.0 g/m2 every day. The 26 patients treated in steps 1 and 2 (range, < 1-6 months) had colon, prostate, or bladder cancer. In step 3, six cancer-free subjects at risk for colorectal cancer received 0.5 g/m2 every day for 5-12 months. To evaluate the effectiveness of DFMO in reducing TPA-induced ODC activity, we calculated the percent change from pretreatment ODC levels in skin biopsy specimens and the percentage of subjects with at least a 50% reduction in ODC levels. RESULTS: In step 1 of the study, treatment-limiting audiotoxicity was observed at the three highest doses. Because the only dose with no major toxic effects in step 2 was 0.5 g/m2 every day, that dose was administered in step 3, with no major toxic effects. Seven subjects treated with 0.5 g/m2 every day had pretreatment ODC levels in the normal range; five averaged a reduction in ODC activity of at least 50%. DFMO had linear pharmacokinetics over the entire dose range. When 0.5 g/m2 was given every day, the peak plasma concentration was 47.1 +/- 5.1 microM at 3-4 hours (monthly mean +/- SE, 14.5 +/- 5.2 microM); half-life was 3.5 hours; and area under the curve for plasma concentration x time for a single dose of DFMO was 311 +/- 39 microM x hour. CONCLUSIONS: These data support phase II chemoprevention studies with DFMO given at a dose of 0.5 g/m2 every day. IMPLICATIONS: Studies investigating prevention of cancers with DFMO are under consideration. PMID- 8478960 TI - Social support and cancer screening among older black Americans. AB - BACKGROUND: Age-adjusted cancer mortality is 27% higher for Black Americans than for the general U.S. population, which may result from inappropriate use of cancer detection tests. Social support has been shown to affect adjustment to breast cancer and survival, but it has not been studied as a predictor of use of preventive health care services in the older population. Our hypothesis is that larger social networks are associated with greater utilization of cancer screening tests in the older population. PURPOSE: The objective of this study was to examine the relationship between social support and use of cancer-screening tests among older Black Americans. METHODS: Data for this study were obtained from a 1986 baseline survey evaluation of a community intervention program to increase cancer awareness and a 1991 end-point survey of use of cancer detection tests. Our study sample consisted of 617 Black Americans aged 55 years or older who lived in San Francisco (Calif.), the control community, and in Oakland (Calif.), the target community for intervention. The survey included measures of 1) social network characteristics, as determined by a modified version of Berkman and Syme's Social Network Index; 2) demographic characteristics; and 3) use of six cancer-screening tests--mammography, occult blood stool examination, cervical smear, clinical breast examination, digital rectal examination, and sigmoidoscopy. RESULTS: Multiple logistic regression analysis of the Social Network Index results indicated statistically significant positive associations of social support with the use of mammography and occult blood stool examination but not with the other cancer-screening tests. There were statistically significant associations between having HMO (Health Maintenance Organization) insurance and increased use of mammography and occult blood stool examination, compared with having Medi-Cal or other insurance. The interval between the surveys had a statistically significant positive association with use of mammography. These significant associations were not explained by differences in the other variables, which included health status, age, gender, education, type of health insurance, interval between the surveys, and a regular source of care. CONCLUSIONS: Social support seems to be associated with increased use of mammography and occult blood stool examinations among older Black Americans. IMPLICATIONS: Interventions designed to increase utilization of social networks may be an effective way to increase use of cancer screening, which may ultimately lead to reduced mortality from cancer. PMID- 8478961 TI - Oral cavity cancer in non-users of tobacco. PMID- 8478962 TI - Re: Environmental tobacco smoke and lung cancer risk in nonsmoking women. PMID- 8478964 TI - Sexual orientation, gender orientation. PMID- 8478963 TI - Re: Environmental tobacco smoke and lung cancer risk in nonsmoking women. PMID- 8478965 TI - The gift of health: yours to enjoy, yours to destroy. PMID- 8478966 TI - President Clinton's managed competition proposal. AB - In the search for fairness of access to health care, value for the money spent, and high quality of patient care, the United States has vacillated between advocacy of government regulations (the 1970s) and of market-driven, pro competitive (1980s) approaches. The possible enactment of President Clinton's health reform plan with a managed-care strategy (1990s) calls for paying physicians and other providers in a manner that often induces them to minimize the provision of services to patients per episode of illness. This article discusses the impact of such legislation on patients, physicians, and other providers. It then argues that the President's managed competition approach, which micromanages health-care services, will fail except by concurrently implementing his proposed National Health Board's global budgetary concept. The major reason is that health reform for the 36.6 million uninsured Americans, who are mostly the working poor and their dependents, is only practical and affordable if stringent policies are adopted that reorganize available health care resources and simultaneously implement cost-containment constraints. PMID- 8478967 TI - Plasma glucose and insulin responses to oral glucose loading in nonobese Nigerian subjects with essential hypertension. AB - In assessing the relationship between insulin levels and blood pressure, we analyzed glucose and insulin data after standard 75 g oral glucose tolerance tests in 16 nonobese male Nigerian subjects with essential hypertension and compared their results with those obtained from 16 age- and sex-matched healthy normotensive subjects. The fasting plasma glucose and insulin as well as 2-hour postload insulin values were similar in both groups. The hypertensive subjects had significantly greater 2-hour glucose levels, larger incremental areas under the glucose/time curves, and smaller ratios of incremental insulin to incremental glucose areas (P < .05). These parameters suggest some impairment of glucose tolerance in the hypertensive subjects related to an inadequate insulin response to the oral glucose load. Model analysis of the glucose and insulin data confirmed these observations in that the estimated rate of glucose uptake into peripheral tissues (M value) was lower in the hypertensive subjects (P = .02). There was no correlation at any time point between insulin values and blood pressure in either group of subjects. These results suggest that essential hypertension in Nigerian diabetic subjects is associated with a reduced insulin response to glucose loading, which is at variance with reports in whites, and deserve further investigation. PMID- 8478968 TI - Altered coagulability: an aid to selective breast biopsy. AB - Difficulty in discriminating nonadvanced breast cancer from benign breast disease results in many cancer negative biopsies. Development of a test to better differentiate between these two entities to reduce the number of cancer negative biopsies was the purpose of this blind study. The clue that prompted the development of this test resides in the state of hypercoagulability in cancer. Hypercoagulability can be measured by assessing tissue factor-mediated altered coagulability. The amount of tissue factor release is contingent on prior activation of the monocyte (the only blood cell that generates tissue factor) in vivo. PMID- 8478969 TI - Barriers to medical care for white, black, and Hispanic American children. AB - As demonstrated by efforts to expand Medicaid coverage for poor and needy children, removing barriers to medical care continues to be an important social policy goal. Data from the 1987 National Medical Expenditure Survey, a multistage probability sample of 15,000 US households, was used to examine some of the barriers that black and Hispanic children encounter in obtaining access to medical care. Results from the 1987 study indicate that black and Hispanic children were more likely than white children to be poor, uninsured members of single-parent households, and to have to wait longer to see a medical provider. Yet differences in waiting time at the usual source of care remained after controlling for insurance. In 1987, 18.6% of uninsured white children were without a usual source of care compared with 28.4% and 25.2% of uninsured black and Hispanic children, respectively. Furthermore, 17.6% of uninsured white children made at least one routine visit to a physician during 1987, while only 11.4% and 10.6% of the uninsured black and Hispanic children, respectively, saw a physician for a regular checkup. PMID- 8478970 TI - The association between serum albumin and HDL and total cholesterol. AB - Relatively low serum albumin is a predictor of increased mortality and coronary heart disease incidence. To shed light on the likelihood of confounding this association by high-density lipoprotein (HDL) cholesterol or other risk factors, data from the National Center for Health Statistics were examined. Serum albumin concentration was significantly correlated with HDL cholesterol concentration only in white men aged 25 to 34 and 35 to 44 years. Serum albumin was positively correlated with serum total cholesterol. Several other cardiovascular risk factors were correlated with serum albumin in whites and blacks. Further studies are needed. PMID- 8478971 TI - Short-term declines in CD4 levels associated with cocaine use in HIV-1 seropositive, minority injecting drug users. AB - This study evaluates the association of cocaine use with short-term change in CD4 counts among human immunodeficiency virus type 1 (HIV-1) seropositive, minority injecting drug users prior to the introduction of zidovudine (AZT). Ninety-eight HIV-1 seropositive subjects were recruited from six inner-city, methadone maintenance clinics. A baseline assessment included a short questionnaire regarding drug behavior and quantitation of CD4 cell counts. These measures were repeated on all subjects 3 to 4 months later. Thirty-eight subjects reported using cocaine between baseline and 4-month follow-up evaluations. Males and African Americans were more likely to be cocaine users (P < .01). Cocaine users were more likely to engage in heroin and needle use (P < .001). Cocaine users experienced a significant decline in CD4 cells compared with nonusers (P = .013); no marked difference in CD4 decline was noted between heroin users and nonusers (P = .19). Multivariate analysis showed that a decline in CD4 counts was 2.82 times more likely to occur in cocaine users than in cocaine nonusers (90% two sided confidence interval of 1.08, 7.37). These findings support the hypothesis of a possible link between cocaine use and short-term CD4 decline in HIV-1 seropositive injecting drug users. PMID- 8478972 TI - The role of nonoperative management of the injured spleen. AB - The role of selective nonoperative management of blunt splenic injuries in adults has been the focus of considerable controversy over the last decade. This article reviews the markedly contrasting experiences of proponents and opponents of this approach. When strict selection criteria are applied (ie, hemodynamic stability, opportunity for close observation, and radiographic confirmation of severity of injury), nonoperative management of blunt splenic injuries can be expected to be successful in more than 80% of cases where it is applied. However, these same criteria would select only about one-quarter of adults with blunt splenic injuries for nonoperative management, and mandate early surgery in the remaining three fourths. There is a limited role for nonoperative management of adults with blunt splenic injuries. The greatest contribution to increasing splenic salvage, however, can be expected to come from improved techniques in operative splenic repair. PMID- 8478973 TI - The effects of lithium therapy on leukocytes: a 1-year follow-up study. AB - Lithium carbonate is a well-established drug for the treatment of manic depressive illness. Leukocytosis is also a common finding in patients given lithium salts, but a few studies have addressed the possibility of persistent leukocyte elevation during long-term lithium therapy. We observed leukocyte counts in 10 manic-depressive patients over a 1-year period after establishing prelithium leukocyte baselines. During the first few weeks, all patients showed significant increases, which persisted throughout the course of treatment. However, there was no significant correlation between plasma lithium levels and leukocytosis. Additionally, there was a significant correlation between lithium dose and leukocytosis. Although leukocytosis is not always a consistent finding in patients on long-term lithium therapy, the persistence of white blood cell elevation in our patient population suggests that lithium might be useful in the long-term management of certain leukopenic conditions using lower-than conventional doses. PMID- 8478974 TI - Passive marijuana usage and water intoxication. AB - This article reports a case of a 3-month-old male presenting with hyponatremic seizure and hypothermia. The presence of marijuana in the infant's urine was remarkable. An etiologic role for the drug is questioned. A review of the literature is provided and the hypothesis of child neglect in the genesis of water intoxication is explored. PMID- 8478975 TI - Atypical desmoid tumor of the abdomen: a case report. AB - Desmoids are rare lesions that are histologically benign but locally aggressive. These lesions should be considered in patients who present with abdominal masses, particularly if there is a prior history of familial polyposis. This case report describes a patient with an abdominal desmoid that demonstrated atypical features on computed tomography and correlative magnetic resonance images. PMID- 8478976 TI - Hughenna L. Gauntlett, MD, FACS: a profile in courage. PMID- 8478977 TI - Mercuric chloride affects protein secretion in rat primary hepatocyte cultures: a biochemical ultrastructural, and gold immunocytochemical study. AB - The toxicity of mercury on hepatocytes was studied at the ultrastructural, biochemical, and immunocytochemical levels. Albumin metabolism was examined because it is a representative liver-specific function. A novel cytochemical method using the protein A-gold technique for the in situ localization of albumin in hepatocyte cultures was applied. Primary rat hepatocyte cultures were exposed to increasing HgCl2 concentrations. Cytotoxicity was assessed by measuring the release of lactic dehydrogenase from the cells. At the highest exposure concentration tested (50 microM), Hg was found to be significantly cytotoxic in contrast to what occurred at 5.0 and 0.5 microM. The level of albumin secreted, as measured by ELISA, was decreased by approximately 38% at 5.0 microM HgCl2 and was found not to be different from that of controls at lower concentrations. The ultrastructural analysis showed that hepatocytes treated with 5.0 microM HgCl2 undergo drastic morphological changes such as a decreased number of ribosomes associated with the rough endoplasmic reticulum, and the disappearance of the latter organelle, proliferation of the smooth endoplasmic reticulum, and dilatation of both the Golgi apparatus and the biliary canaliculus-like structures. Immunocytochemical detection of albumin-immunoreactive sites using protein A-gold labeling further revealed that these were less abundant in hepatocytes treated with 5.0 microM HgCl2 (-64%) as compared to control preparations. These results suggest that one of the effects of mercury on hepatocytes is to affect liver-specific functions such as albumin production, possibly through interference with ribosomal function. This study also demonstrates for the first time the applicability of the high-resolution protein A-gold technique for toxicological investigations on hepatocytes in vitro. PMID- 8478978 TI - Absorption of polycyclic aromatic hydrocarbons through human skin: differences between anatomical sites and individuals. AB - In order to determine differences in absorption of polycyclic aromatic hydrocarbons (PAH) between anatomical sites and individuals, coal-tar ointment was applied to skin of volunteers at various sites. The surface disappearance of PAH and the excretion of urinary 1-OH-pyrene after skin application of coal-tar ointment were used as parameters for dermal PAH absorption. The surface disappearance was determined by the measurement of the fluorescence of PAH on skin. Surface disappearance measurements show low but significant differences in dermal PAH absorption between anatomical sites: shoulder > forehead, forearm, groin, > ankle, hand (palmar site). The average PAH absorption rate constant at different skin sites ranges from 0.036/h to 0.135/h (overall mean: 0.066/h). This indicates that after 6 h of exposure, 20-56% of a low dermal dose of PAH (e.g., about 1.0 ng pyrene/cm2) will be absorbed. The interindividual differences in PAH absorption are small (7%) in comparison with differences between anatomical sites (69%). Results based on the urinary excretion of 1-OH-pyrene are less clear. The site of application of the coal-tar ointment (dose: 2.5 mg/cm2 during 6 h) has no significant effect on the excreted amount of 1-OH-pyrene in urine. It is estimated that after coal-tar ointment application on skin, 0.3-1.4% of the pyrene dose (about 2 micrograms pyrene/cm2) becomes systemically available. For the accurate estimation of PAH uptake through skin of workers, it seems relevant to distinguish different body regions, not only because of the regional variation in percutaneous PAH absorption, but also because of the high dispersal of PAH contamination on skin of workers. PMID- 8478979 TI - Effect of pyridine on the hepatic and pulmonary metabolism of 2-butanol in rat and rabbit. AB - Pyridine has been shown to be an effective inducer of the ethanol-inducible cytochrome P-450IIE1 in both liver and lung. The oxidation of 2-butanol by rat liver is inducible by chronic ethanol consumption. The purpose of this study was to determine the effect of pyridine on the hepatic and pulmonary metabolism of butanol. Comparisons were made between rat and rabbit. Acute pyridine treatment (200 mg/kg, ip) increased hepatic metabolism of 2-butanol in the rat twofold and in the rabbit threefold. The effect of pyridine on hepatic butanol oxidase is similar to the effect reported by other investigators for ethanol administered in the drinking water for 3 wk. Control rabbit pulmonary butanol oxidase activity was 10-fold higher than that in the rat. Pyridine decreased pulmonary butanol oxidase activity in the rabbit. The effect was demonstrated both in vitro and in the isolated perfused rabbit lung. Pyridine had no effect on pulmonary butanol oxidase activity in the rat. PMID- 8478980 TI - Recovery potential of hepatocytes from inhibition of albumin secretion by cadmium. AB - The aim of this study was to examine albumin production, a typical liver-specific function, in hepatocytes treated with Cd and to examine the reversibility of the perturbations induced by the toxic metal. Cultures of freshly isolated rat hepatocytes were exposed to increasing amounts of Cd in modified Leibowitz L-15 medium for 20 h; the cells were then allowed to recover by further incubation in Cd-free medium for an additional period of 20 h. The levels of albumin secreted into the extracellular medium were determined by enzyme-linked immunosorbent assay and were found to be reduced by Cd in a concentration-dependent fashion over the first 20 h. Inhibition was seen at Cd concentrations that did not cause any loss of cellular viability (up to 0.5 microM Cd), as judged from the release of lactate dehydrogenase by the cells. After replacement of the exposure medium by Cd-free medium, the same pattern of diminished albumin secretion was obtained, revealing the persistence of the cytotoxic effects when recovery conditions were applied. Moreover, hepatocytes exposed to 0.5 microM Cd for 20 h and processed for visualization of albumin immunoreactive sites using protein A-gold and electron microscopy exhibited very low albumin-specific labeling as compared to the controls (0.6 +/- 0.05 vs. 20.0 +/- 2.6 gold particles/micron2). Intracellular glutathione levels were not significantly changed by Cd either after the initial exposure or after the incubation that followed in control medium. The accumulation of Cd by the cells, as measured by graphite furnace atomic absorption spectrophotometry, was concentration dependent. It remained stable after medium change, indicating that Cd efflux was negligible upon reestablishment of normal conditions. The present data show that the perturbations in albumin metabolism caused by Cd are not readily alleviated after the cells are returned to Cd-free medium, suggesting a limited short-term recovery potential against cytotoxic damage. The data also demonstrate that hepatocyte-specific functions can be used as sensitive indicators for the detection of cellular disturbances by hepatotoxins. PMID- 8478981 TI - Toxicological effects of ziram, thiram, and dithane M-45 assessed by sperm shape abnormalities in mice. AB - The three commonly used dithiocarbamate fungicides ziram, thiram, and dithane M 45 were investigated for their mutagenic and carcinogenic potency using sperm shape abnormalities in mice. The fungicides were administered intraperitoneally in single and cumulative doses. All three of the fungicides tested were found to induce significant increase in the frequency of abnormal sperm at all the doses, and a linear dose effect was observed. PMID- 8478982 TI - Effects on thyroid hormone metabolism and depletion of lung vitamin A in rats by airborne particulate matter. AB - Thyroxine (T4) and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Thyroid hormone and vitamin A metabolism are linked by a common plasma carrier protein, transthyretin (TTR). Polychlorinated biphenyls (PCBs) and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and alteration of their metabolism in hepatic and other organs. In the present report an outdoor airborne particulate matter (APM) extract was tested for both interaction with thyroid hormone and vitamin A metabolism, in order to address the question of whether APM has the potency to deplete vitamin A and thyroid hormones. Furthermore, studies were performed to characterize compounds present in APM that interact with TTR. A third aim was to compare the interaction of APM extracts with TTR and thyroxine-binding globulin (TBG), the major carrier protein for thyroxine in humans. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and increased plasma retinol levels gradually over the time period studied, while liver retinol, lung retinol, and retinyl palmitate levels were depleted by 30 50%. As outdoor APM was able to inhibit T4-TTR binding in vitro, this suggests that the reduction in thyroxine levels in vivo is caused by the same phenomenon. Experiments showed that the neutral fraction of the APM extract accounted for most of the inhibitory activity on T4-TTR binding. Polycyclic aromatic hydrocarbons and nitrated derivatives are not likely to be responsible for the activity of the neutral fraction, because several representatives of these compounds showed no or very little interaction with TTR. Pentachlorophenol, a compound with known inhibitory activity on T4-TTR binding, was detected in the organic acid fraction of both a cigarette smoke sample and an outdoor APM sample. Finally, it was shown that several indoor and outdoor APM extracts only interact with TTR, but not with TBG. As APM has the potency to deplete lung vitamin A in vivo and vitamin A might have a protective effect in the process of lung carcinogenesis, APM might increase the susceptibility for the development of lung cancer. PMID- 8478983 TI - Airway inflammatory effect of hydrogen peroxide in guinea pigs. AB - Reactive oxygens are now considered to be important substances in promoting inflammatory process. Recently, airway inflammation has attracted attention closely linked to bronchial asthma. The present study was undertaken to examine whether hydrogen peroxide, one of the reactive oxygens, could produce airway inflammation. Airway inflammation was assessed by airway vascular permeability in terms of pontamine sky blue (PSB) exudation. Airway resistance was measured with a modified Konzett-Rossler method and was expressed as a change in ventilation overflow. Inhalation of hydrogen peroxide (0.01-1.0 M) markedly caused a PSB exudation in a concentration-dependent manner in all of the trachea, main bronchus, and lungs. The hydrogen peroxide-induced PSB exudation effect was attenuated was attenuated by pretreatment with catalase, although heat inactivated catalase had no inhibitory effect. Deferoxamine, which inhibits conversion of hydrogen peroxide into hydroxyl radical, decreased the PSB exudation induced by hydrogen peroxide. On the other hand, inhalation of hydrogen peroxide (1.0 M) caused a significant and biphasic increase in ventilation overflow. This airway constriction was suppressed by pretreatment with inhaled catalase, but not by inhaled deferoxamine. These results indicate that hydrogen peroxide causes an intense airway inflammation; this inflammatory effect may be mediated not only by hydrogen peroxide itself but also by hydroxyl radical. Hydrogen peroxide and hydroxyl radical may thus play an important role in bronchial asthma and bronchitis through inducing airway inflammation. PMID- 8478984 TI - Interferon-gamma inhibits DNA synthesis and insulin-like growth factor-II expression in human neuroblastoma cells. AB - Interferon-gamma (IFN-gamma) is known to be an antiproliferative, differentiating agent in many cell types, including neuroblastoma. In this study, we determined the effects of IFN-gamma on cellular growth and expression of insulin-like growth factor II (IGF-II) and IGF receptors in the human neuroblastoma cell line SH SY5Y. Incubation of SH-SY5Y cells in IFN-gamma (20-100 U/ml) induced the formation of long neuritic processes. IFN-gamma treatment also induced decreases in [3H]TdR incorporation, as well as serum-dependent changes in cell number. Treatment with IFN-gamma reduced cell number 33% in the presence of serum but had no effect on cell number in the absence of serum. IGF-II mRNA content was 60% inhibited by IFN-gamma, and was not serum dependent. The concentration of immunoreactive IGF-II in SH-SY5Y conditioned medium was also reduced in the presence of IFN-gamma, to less than half of control levels. In contrast, type I IGF receptor mRNA content was increased more than three-fold after treatment with IFN-gamma and serum. Co-incubation in IFN-gamma (20-100 U/ml) and IGF-II (3-10 nM) prevented the inhibitory effects of IFN-gamma on [3H]TdR incorporation in serum-free media. Our results suggest that IFN-gamma may inhibit DNA synthesis and cell growth by interfering with an IGF-II/type I IGF receptor autocrine growth or survival mechanism. PMID- 8478985 TI - Basic fibroblast growth factor expression is required for clonogenic growth of human glioma cells. AB - Basic fibroblast growth factor (bFGF) is a heparin-binding protein, expressing potent mitogenic and angiogenic properties. Elevated levels of bFGF have been identified in human gliomas and glioma cell lines, suggesting that bFGF expression is involved in the aberrant growth patterns associated with these tumors. In the present study, the influence of bFGF on additional parameters of glioma cell malignancy was evaluated utilizing three distinct methods to suppress bFGF expression or activity including antisense oligonucleotide primers, a neutralizing monoclonal antibody or an inhibitor of the agonist action of bFGF: (1) The addition of 30 microM bFGF-specific antisense oligonucleotide primer to the human glioma cell line SNB-19 resulted in a 55% inhibition in colony formation in soft agar. This effect was dose-dependent and specific, as sense strand primer was ineffective in suppressing growth. In addition to exhibiting fewer colonies, antisense treatment significantly altered colony morphology. (2) SNB-19 cell growth in culture was suppressed in the presence of a neutralizing bFGF-specific monoclonal antibody. (3) Inositolhexakisphosphate, a newly identified antagonist of FGF binding and activity, suppressed SNB-19 cell growth in soft agar culture. These results demonstrate that bFGF may regulate glioma growth and progression independent of its role in tumor angiogenesis and that bFGF release or secretion may be required for these actions. PMID- 8478986 TI - Neuropeptide Y-producing neurons of the arcuate nucleus regenerate axons after surgical deafferentation of the mediobasal hypothalamus. AB - Dorsolateral and ventomedial surgical deafferentiation of the hypothalamus were used to study the capacity of different types of neuropeptide Y-containing axons afferent to the dorsal hypothalamus to regenerate through surgical lesions. The kinetics of the postlesional responses of transected neuropeptide Y-axons was studied on 30-40 microns thick vibratome sections, either (i) by light or electron microscopy after peroxidase immunostaining for neuropeptide Y or (ii) by confocal microscopy after double fluorescence immunostaining for neuropeptide Y and for glial fibrillary acidic protein. The dorsolateral cut was found to sever 2 main pathways containing neuropeptide Y axons located, respectively, below the bed nucleus of the stria terminalis and in the perifornical region. In both regions transected fibers were found to abut onto the surgical lesion, but even 45 days after the lesion, they were very rarely observed to penetrate into the astroglial scar forming along the lesion. The ventromedial cut was found to sever numerous neuropeptide axons that originate in the underlying arcuate nucleus. Seven to 15 days after the lesion neuropeptide Y fibers located below this type of cut presented a dramatic increase in both their numerical density and their immunostaining intensity. With increasing post-surgery times, an increased number of neuropeptide Y fibers was observed to penetrate and to cross the lesional scar formed by densely packed astrocytic processes. Electron microscope observations further demonstrated that 45 days after the lesion, numerous neuropeptide Y immunoreactive axonal profiles were included in the scar matrix, which appeared to be mainly composed of closely interdigitating astrocytic processes containing dense bundles of filaments. These data indicate that, in contrast to other neuropeptide Y neurons innervating the dorsal hypothalamus, neuropeptide Y neurons of the arcuate nucleus regenerate axons through the astroglial scar produced by a surgical lesion placed in the ventromedial hypothalamus. PMID- 8478987 TI - Reactive astrocytes involved in the formation of lesional scars differ in the mediobasal hypothalamus and in other forebrain regions. AB - The fine organization of lesional scars was studied in adult rats at the level of 2 types of surgical cuts aimed at deafferentating the dorsal hypothalamus from its neuropeptide-Y innervation. These included: (i) lesions located dorsolateral to the dorsal hypothalamus, which were shown to form a permanent obstacle to the regeneration of transected neuropeptide-Y-fibers, and (ii) lesions located in the ventromedial hypothalamus, where transected neuropeptide-Y-fibers were shown to penetrate and eventually cross the lesional area. Double labeling immunocytochemistry and conventional electron microscopy were used to identify various molecules produced by reactive astrocytes and to visualize their ultrastructural organization within the scars, respectively. In the different portions of the dorsolateral scars, the large majority of reactive astrocytes was characterized by a strong immunoreactivity to glial fibrillary acidic protein, vimentin, and embryonic (polysialylated) NCAM. Intense laminin-immunoreactivity was also observed over large patches included in the scar. Electron microscope observations further indicated that the matrix of the scar was mainly composed of tightly packed astrocytic perikarya and processes connected by extended gap junctions. All around the extracellular and perivascular spaces, these astrocyte profiles were bordered by a thick basal lamina. Only scarce axonal profiles were detected in the core of the scar, most of which exhibited degenerative features. In the ventromedial hypothalamic scars, reactive astrocytes were found to exhibit intense immunoreactivity to both glial fibrillary acidic protein and vimentin. On the other hand, only slight immunostaining to embryonic NCAM and laminin were associated with this type of lesional scar. At the ultrastructural level, the main differences with the dorsolateral scars concerned (i) the gap junctions, which were less frequent and involved shorter portions of adjacent membranes; (ii) the basal lamina, which was essentially localized to the perivascular spaces; and (iii) the axonal profiles, which were frequently observed throughout the scar matrix. These data indicate that reactive astrocytes that formed the glial scar differ in the mediobasal hypothalamus and in other forebrain regions. This provides strong support for the hypothesis that the regeneration of neuropeptide-Y axons through a mediobasal hypothalamic surgical cut depends mainly on the particular organization of the astroglial scar. PMID- 8478988 TI - Interleukin-4 and -5 as modulators of nerve growth factor synthesis/secretion in astrocytes. AB - To examine the regulation of nerve growth factor (NGF) gene expression with respect to neural trauma, we examined the effects of T cell-derived lymphokines on NGF synthesis/secretion in cultured mouse astrocytes. Interleukin (IL)-4 and IL-5 significantly increased the amount of NGF secreted by astrocytes, whereas IL 2, IL-3, and IL-6 had no significant effect. IL-4 and IL-5 produced marked increases in NGF mRNA levels in astrocytes as demonstrated by the reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of IL-4 and IL-5 was greater in quiescent astrocytes than in growing cells. Neither increase in thymidine incorporation nor any morphological change was observed during the treatment with IL-4 and IL-5. The stimulatory effect of IL-4 and IL-5 on NGF synthesis was completely inhibited by the addition of anti-IL-4 monoclonal antibody and anti-IL-5 monoclonal antibody, respectively. The results indicate that IL-4 and IL-5 specifically trigger a cascade of events to regulate NGF synthesis in astrocytes, independent of cell growth. PMID- 8478989 TI - Blockage of nicotinic acetylcholine receptors by 5-hydroxytryptamine. AB - The action of 5-hydroxytryptamine (5HT) on nicotinic acetylcholine receptor (nAChR) channels was investigated in mouse myotubes, human cloned TE671/RD cells, and Xenopus laevis oocytes. The decay of the ACh-activated whole-cell currents was reversibly accelerated in the presence of 5HT (10(-5) to 10(-3) M), in a dose dependent manner. 5HT also reduced the size and accelerated the decay of currents elicited by ACh in Xenopus oocytes injected with mRNA extracted from C2 myotubes or Torpedo electroplaques, or oocytes injected with cloned mouse muscle AChR subunit mRNAs. The effect of 5HT was promptly reversed after washout, or by depolarizing the oocyte beyond -10 mV. In patch-clamp recordings from myotubes, bath-application of 5HT did not exert an indirect influence on the ACh-activated channels within the patch membrane. In contrast, when the patch membrane was exposed to 5HT (10(-6) M), ACh unit responses appeared as bursts of short pulses. It is concluded that the regulation of ACh responses by 5HT results from a fast noncompetitive blocking action of nAChR-channels. These results show that ligand gated channels, activated by their specific neurotransmitter, may be regulated by a different neurotransmitter through a direct action on the receptor molecule. PMID- 8478990 TI - Rat cerebral cortical neurons in primary culture release a mitogen specific for early (GD3+/04-) oligodendroglial progenitors. AB - The development of cells of the oligodendroglial lineage, from immature progenitor to myelinating cells, occurs largely in a neuronal environment, yet little is known about specific interactions between these 2 cell types. We have tested the effects of medium conditioned by cultures of rat cerebral cortical neurons (CCM), cerebellar granule interneurons (GCM), and a dorsal root ganglion derived cell line (NDCM) on cells of the oligodendroglial lineage in culture. Different stages of the lineage were defined using the cell surface antigens GD3, 04, and GalC. CCM and NDCM were mitogenic for the early GD3+/04- oligodendroglial progenitor, whereas GCM was mitogenic for the later GD3+/04+ stage. Neutralising antibodies to PDGF and bFGF were able to eliminate the mitogenic activity of NDCM and GCM, respectively, but did not abolish the mitogenic effect of CCM. We have demonstrated that neurons in primary culture from distinct CNS regions exert different influences on cells of the oligodendroglial lineage, and specifically that cortical neurons release an unknown mitogen for GD3+/04- oligodendroglial progenitors. PMID- 8478991 TI - The acute haemodynamic effects of captopril in dogs with heart failure. AB - The acute effects of three doses of captopril (12.5, 25, and 50 mg [approximately 0.5, 1.0, and 2.0 mg/kg]) on several haemodynamic variables and plasma aldosterone concentration were investigated in four dogs with experimentally produced heart failure (rapid ventricular pacing) and one dog with dilated cardiomyopathy. Haemodynamic variables were measured with a Swan-Ganz thermodilution catheter and an indwelling carotid artery catheter at baseline and 1, 2, and 4 h after drug administration. A statistically significant (P < 0.05) decrease in peripheral vascular resistance was observed 1 and 2 h following the 12.5 mg dose. A significant and large enough decrease in peripheral vascular resistance to produce a significant decrease in mean systemic arterial blood pressure was observed 1 and 2 h after administering 25 and 50 mg of captopril. A mild but significant increase in cardiac output was observed 1 h after each dose. The drug effect on systemic arterial blood pressure lasted less than 4 h. No statistically significant changes were observed for the group in pulmonary capillary wedge pressure, right atrial blood pressure, or plasma aldosterone concentration at any time. We conclude that the acute haemodynamic benefits provided by captopril administration were mild and due primarily to arteriolar dilation. Doses of approximately 1-2 mg/kg produced slightly greater arteriolar dilation than an approximate dose of 0.5 mg/kg. The drug effect was short-lived, lasting less than 4 h. PMID- 8478992 TI - Theophylline kinetics in dog neonates. PMID- 8478993 TI - Compared N-demethylation of veterinary drugs by microsomes from normal and fluke infected sheep livers. PMID- 8478994 TI - Pharmacokinetics of sulphadiazine and trimethoprim in carp (Cyprinus carpio L.) acclimated at two different temperatures. PMID- 8478995 TI - Effect of intra-ovarian 6-hydroxydopamine on progesterone secretion in sheep. PMID- 8478996 TI - Lack of arrhythmogenicity of aminophylline in dogs. AB - This study was designed to determine if doses of aminophylline up to 10 mg/kg given i.v. would produce ventricular arrhythmias in seven healthy dogs anaesthetized with fentanyl-droperidol-pentobarbital. Arrhythmias were sought by inspection of ECGs before and after attempts at provoking them with 5 micrograms/kg boluses of epinephrine given i.v., or by programmed electrical stimulation. After cumulative doses of 10 mg aminophylline/kg body weight, producing an estimated plasma concentration of greater than 30 micrograms/ml, no ventricular ectopia other than escape depolarizations were observed. We were unable to document an arrhythmogenic effect of aminophylline when given rapidly by the i.v. route. It is possible that the anaesthetic regimen reduced the arrhythmogenic property of aminophylline, or that arrhythmias might be produced in either obese or ill dogs; but it is unlikely that chronic administration of aminophylline would be more arrhythmogenic. PMID- 8478997 TI - Pharmacokinetic disposition of intravenous and oral pentoxifylline in horses. AB - The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 +/- 0.67 h), had a large steady-state volume of distribution (2.81 +/- 1.16 l/kg), and high clearance (3.06 +/- 1.05 l/kg/h). Oral absorption of pentoxifylline from both dose forms varied considerably between individuals. Times to peak concentration ranged from 1-10 h for either dose form. There was no difference in relative bioavailability (F') between whole (0.98 +/- 0.30) and crushed Trental tablets. Ratios between areas under the curve (AUC) for pentoxifylline and MI were different following administration of oral versus intravenous doses. This finding suggests that route of administration may affect the metabolic profile of pentoxifylline. Given the extreme differences in absorption characteristics between individuals in this study, recommendations are not made as to appropriate dose, dose interval, or dose form for administration of pentoxifylline to horses. PMID- 8478998 TI - Nicarbazin stimulates intestinal transport of L-leucine in rabbit. AB - Nicarbazin is an anticoccidial drug used mainly in birds, but also in rabbits. Besides the anticoccidial activity, nicarbazin has shown several other effects such as inhibition of growth and feed efficiency in poultries, and stimulation of sugar intestinal absorption in rabbits. The present work has been performed in order to check whether nicarbazin also affects L-leucine intestinal absorption. The results obtained show that nicarbazin decreases L-leucine accumulation in the jejunal tissue, and increases mucosal to serosal transepithelial fluxes of this amino acid in a dose-dependent way, without modifying its diffusion across the intestinal epithelium. The drug stimulates the amino acid uptake in brush-border and basolateral membrane vesicles, thus suggesting that nicarbazin increases the absorption of L-leucine mediated by carriers. PMID- 8478999 TI - Gastrointestinal distribution of albendazole metabolites following netobimin administration to cattle: relationship with plasma disposition kinetics. AB - The gastrointestinal (GI) distribution and plasma disposition kinetics of albendazole (ABZ) metabolites after oral administration of netobimin (NTB) to cattle were studied. Eight Holstein steers (150-180 kg) were surgically fitted with permanent cannulae in the rumen, abomasum and ileum. After post-surgical recovery, the animals were treated orally with a suspension of netobimin zwitterion (400 mg/ml) at 20 mg/kg. Jugular blood and ruminal, abomasal and ileal fluid samples were taken serially over a 96 h period and analysed by HPLC for NTB and its metabolites, including ABZ, ABZ sulphoxide (ABZSO), ABZ sulphone (ABZSO2) and amino-albendazole sulphone (NH2ABZSO2). NTB parent drug was only found in the GI tract and for only 12-18 h post-treatment. ABZSO and ABZSO2 were the main metabolites found in plasma, being present for 30-36 h. These metabolites were exchanged between plasma and different GI fluids and were greatly concentrated in the abomasum. This phenomenon may account for the presence of ABZ, ABZSO and ABZSO2 in the GI tract for 72 h post-treatment despite the fact that ABZ was not detected in plasma and ABZSO and ABZSO2 were detected for only 30-36 h in plasma. The presence of ABZ and ABZSO in the abomasum and intestine for this extended period of time is probably relevant for anthelmintic efficacy against GI parasites. The NH2 ABZSO2 metabolite was detected in plasma, abomasum and ileum and its disposition kinetics were characterized for the first time. PMID- 8479000 TI - Effects of dietary variations on plasma concentrations of oral flukicides in sheep. AB - Groups of parasite-free lambs which were either housed and fed hay and concentrates or were grazing on pasture were dosed with the oral flukicides rafoxanide and triclabendazole and subsequent plasma concentrations monitored. Peak plasma concentrations and areas under curves (AUC) of both chemicals were significantly reduced in the grazing compared with the housed lambs. In order to investigate the observation similar groups of lambs were dosed orally with chromium EDTA and faecal throughput estimated. It was observed that the rate of throughput was greater in the grazing lambs, leading to the conclusion that the differences in plasma concentrations of the flukicides was caused by a reduction in their absorption in the grazing lambs. The implications on flukicide efficacy and dose rates are discussed. PMID- 8479001 TI - Hormonal regulation of oxidative drug metabolism in the dwarf goat. The effect of sex and hormonal treatment on plasma disposition and metabolite formation of sulphadimidine. AB - Sulphadimidine (20 mg/kg i.v.) plasma elimination and metabolite formation were studied in intact male, castrated male, and female dwarf goats. Plasma pharmacokinetics and urinary metabolite patterns were first studied in untreated animals. Afterward, females and castrated were treated with a combination of testosterone-propionate (1 mg/kg) and 17 beta-oestradiol-benzoate (0.02 mg/kg) once every 3 days, for a period of 4 weeks. In untreated animals, males showed a considerably lower plasma clearance than females or castrates. This was accompanied by lower partial clearances for the production of two hydroxylated sulphadimidine metabolites. After hormonal treatment of females and castrates, sulphadimidine plasma clearance was significantly reduced, to values corresponding with those observed in control males. Furthermore, hydroxylation was significantly inhibited after treatment. The results indicate that sulphadimidine hydroxylation in the goat is performed by enzymes of the cytochrome P450 complex which are strongly influenced by gonadal hormones. Androgens seem to play a central role in this respect. PMID- 8479002 TI - Pharmacokinetics and applications of ampicillin sodium as an intravenous infusion in the horse. AB - A regime for administration of ampicillin sodium by continuous intravenous infusions to horses was designed. The aim was to achieve plasma ampicillin concentrations between 5 and 10 micrograms/ml over a 4-h period. A 2 mg/kg bodyweight loading dose of ampicillin sodium was administered intravenously at the beginning of the infusion in order to achieve steady-state plasma concentrations rapidly. The infusion system subsequently administered ampicillin at a rate of approximately 19.2 micrograms/min/kg bodyweight. The plasma concentrations obtained over the infusion period correlated very well with predicted calculations based on pharmacokinetic parameters. A mean +/- SEM steady state plasma concentration (Cpss) of 5.94 +/- 0.33 was obtained and ampicillin was shown to have an apparent steady-state volume of distribution (Vdss) of 175.43 +/- 13.63 ml/kg. When the pump was disconnected the concentrations declined over the following 4 h in an exponential way with an elimination half life (t1/2 beta) of 0.62 h. In addition, three different infusion dose rates (13.78, 19.34 and 24.48 micrograms/min/kg) were administered to a single animal showing that a good correlation (correlation coefficient > 0.99) existed between the dose administered the steady-state plasma concentrations and the corresponding areas under the plasma concentration versus time curve. PMID- 8479003 TI - Plasma ronidazole concentrations in sheep after intravenous, oral, intraruminal and intraabomasal administration. AB - Plasma ronidazole concentrations were examined after intravenous (i.v.) and oral administration of ronidazole in sheep (n = 6) at a dosage of 5 mg/kg body weight. In three sheep a ruminal and an abomasal fistula were inserted. The ronidazole determinations were performed by an HPLC method. Oral bioavailability in the fistulated sheep was only 5.5 +/- 1.8% (mean +/- SE). Somewhat lower values (4.6 +/- 1.4%) were obtained when the drug was administered through the ruminal fistula in the rumen. After administration of the same dose directly in the abomasum through the intraabomasal fistula, bioavailability was increased to 86.0 +/- 8.9%. In the non-fistulated sheep, oral biodisponibility was 2.6 +/- 0.5%. After water was restricted for 48 h before the oral ronidazole administration to these sheep, bioavailability was slightly increased (6.0 +/- 3.1%). When desmopressin acetate was injected i.v. before the oral ronidazole administration, bioavailability was 10.6 +/- 6.5%. When glypressin, another vasopressin analogue, was used, oral bioavailability was not influenced: 2.4 +/- 1.3%. Ronidazole was also incubated with ruminal contents and the ronidazole concentration decreased with a first order rate constant of 0.122 +/- 0.050 min-1 (mean +/- SE). These results suggest that oral administration of ronidazole to sheep is of little therapeutic use, because most is metabolised by the ruminal micro-organisms before it can reach the circulation. A second conclusion we can make is that it is very difficult, if not impossible, at least with the methods used, to influence gastro-intestinal motility in sheep to get a reproducible closure of the oesophageal groove. PMID- 8479004 TI - Lidocaine decay and hepatic extraction in the pig. AB - Plasma lidocaine decay after injection was studied in five anaesthetized pigs and fitted to a two compartment open model. Derived pharmacokinetic parameters were employed to rapidly achieve plateau concentrations within 60 min of starting a two stage infusion of lidocaine hydrochloride. Hepatic extraction and clearance of lidocaine at steady state were determined in 10 pigs by transhepatic sampling and measurement of hepatic arterial and portal venous blood flow using perivascular ultrasonic flow probes placed at laparotomy. These data were compared with similar studies performed in man as well as the sheep, dog, monkey and cat. The lidocaine extraction ratio of 0.60 in the pig was found to be similar to that determined by others in man. PMID- 8479005 TI - Pharmacodynamics, pharmacokinetics and faecal persistence of morantel in cattle and goats. AB - Morantel could not be detected (< 0.05 microgram/ml) in the plasma of cattle or goats following the oral administration of morantel tartrate at a dose rate of 10 mg/kg bodyweight. No morantel was detected in the milk of lactating goats except in one animal where a concentration of 0.092 microgram/ml was detected at 8 h after drug administration. Morantel was highly effective against Cooperia oncophora infections in calves treated 6, 9 or 18 days after infection; however, was highly effective against Ostertagia ostertagi only when treated 18 days after infection. Morantel did not affect the fecundity of adult O. ostertagi surviving treatment 18 days after infection which had similar average numbers of eggs in their uteri (range 13.4 +/- 0.73-16.8 +/- 0.98) as did parasites from control animals (range 12.0 +/- 0.70-13.6 +/- 0.66). Morantel could be detected at a concentration of 96 +/- 4.5 micrograms/g (dry weight) in the faeces of a calf 24 h after treatment with 10 mg/kg bodyweight of morantel tartrate. The concentration of morantel in replicate samples of this faeces exposed to natural atmosphere, but not to soil or soil organisms, declined slowly over the following 322 days. At day 322 after the start of the experiment 8.8 micrograms/g of morantel could be measured in the remaining faecal material. Throughout the faecal degradation study the concentration of morantel in the crusts of the replicate sample pats was lower than the concentration in the core samples. PMID- 8479007 TI - Special issue: impotence and infertility. PMID- 8479008 TI - Venous impotence: pathophysiology, diagnosis and treatment. PMID- 8479006 TI - Urinary excretion of metals during treatment with D-penicillamine and 2 mercaptopropionylglycine in normal and cystinuric dogs. AB - Urinary excretion of metals during treatment with 2-mercaptopropionylglycine (2 MPG) was studied in 11 normal and 20 cystinuric male dogs. The results were compared with those obtained during D-penicillamine treatment. Twenty-four-h urine and morning samples of urine were taken for determination of 13 metals before and during treatment. After single intravenous and oral D-penicillamine treatment of the normal dogs, significant increases were found in the 24-h urinary excretion of Ca, Cu and Zn. Oral intake of D-penicillamine increased the excretion of Co, Cr, Fe and Mg as well. No effect on renal metal excretion was observed after single intravenous and up to 2 months of daily oral treatment with 2-MPG. In 14 cystinuric dogs no effect was found after single intravenous and oral administrations of 2-MPG. However, after oral treatment of six cystinuric dogs with 2-MPG for 2-4 months, significantly increased excretions of Ca and Mg were found. Fourteen of the cystinuric dogs were also investigated after 2-6 years of continuous 2-MPG treatment, and after this period no significant elevation in the urinary excretion of metals was found. The present study shows that in contrast to D-penicillamine, 2-MPG does not increase the urinary excretion of metals to any appreciable extent. Observed increases in the excretion of Ca and Mg seemed to be a temporary effect only. PMID- 8479009 TI - Diagnosis and treatment of psychogenic erectile dysfunction in a urological setting: outcomes of 18 consecutive patients. AB - The diagnostic criteria and treatment outcomes of 18 consecutive patients with psychogenic erectile dysfunction were examined. Average patient age was 38 years, and all patients had either awakening penile or masturbatory rigidity. Each patient was studied with home monitoring (ART-1000) on 2 consecutive nights. The average number of maximum erectile episodes, the event during which the maximum rigidity was maintained for at least 5 minutes, was 1.6. The maximum sleep erectile episodes averaged 11.2 minutes during which penile rigidity averaged 572 gm. The main predictor for remission of erectile dysfunction in this study was whether the dysfunction was primary or secondary. Of 14 patients with secondary psychogenic erectile dysfunction, that is history of being able to achieve and maintain penile rigidity sufficient for at least 5 minutes of vaginal intercourse, 10 (71%) experienced remission. Three patients noticed spontaneous remission during the initial evaluation and another 3 experienced remission within 3 months of completion of the evaluation and reassurance that they had normal erectile capacity. Two patients had remission while considering penile vascular surgery and in 2 normal erectile function returned during injection therapy. Only 2 of 3 patients referred for sex therapy actually received it (Freudian theory), and neither noticed improvement in erectile function. One patient received yohimbine without benefit. None of the patients elected treatment with the vacuum constriction device. All 4 patients with primary psychogenic erectile dysfunction, that is never able to achieve and/or maintain penile rigidity sufficient to achieve vaginal intercourse, failed to respond to physician reassurance and time. Of 2 patients who received sex therapy (1 Freudian and 1 behavioral) without improvement in erectile function 1 has entered the pharmacological erection program and has achieved vaginal penetration, and the other is considering the pharmacological erection program. The remaining 2 patients have deferred all therapy. Based on this experience, we currently reassure patients with secondary psychogenic erectile dysfunction that they have erectile capacity for sustained vaginal intercourse and schedule a followup visit in 3 months. Additional individualized therapy (pharmacological erection program, vacuum constriction device, sensate focus/psychodynamic specific therapy or penile prosthesis) is offered as needed and requested. Patients with primary psychogenic erectile dysfunction are initially offered the pharmacological erection program or the vacuum constriction device and sex sensate focus/psychodynamic specific therapy. The penile prosthesis is considered for treatment failures. PMID- 8479010 TI - Evaluation of penile deep arteries in psychogenic impotence by means of duplex ultrasonography. AB - Echo Doppler flowmetric investigation in patients with erectile insufficiency represents an effective method for hemodynamic evaluation of the penis. The detection of referential standard parameters is helpful to understand the pathogenesis of the disease, since patients with erectile insufficiency due to psychogenic factors cannot be distinguished from normal subjects by means of current diagnostic techniques. Echo Doppler flowmetry applied to rigorously selected subjects with psychogenic impotence allowed for detection of hemodynamic parameters in the penis after corpora cavernosa stimulation with 10 micrograms. prostaglandin E1. Flowmetric investigation was performed only on the deep cavernous artery, since it is well known that the penile dorsal artery does not undergo hemodynamic alterations after stimulation with drugs. A statistically meaningful difference existed between the systolic flow in the psychogenic impotence subjects (group 1) and the controls (group 2, p < 0.0001). In the same manner, the diastolic flows (right and left cavernous arteries, p < 0.0002 and p < 0.0001, respectively) and diameter increase rates of the investigated arteries following stimulation were also different. According to these results, echo Doppler flowmetry could represent the only instrumental method able to detect patients with psychogenic impotence. PMID- 8479011 TI - Comparison of RigiScan and formal nocturnal penile tumescence testing in the evaluation of erectile rigidity. AB - Evaluation of male erectile function ideally should include measurement of axial rigidity expressed as grams force required to produce penile buckling. An axial rigidity more than 550 gm. is generally considered adequate for vaginal penetration. Unfortunately, this test cannot be done frequently and may disrupt sleep. An alternative method of determining rigidity is to use the RigiScan,* which makes repetitive measurements of radial rigidity at the base and tip of the penis expressed as per cent of normal maximum. Previous studies have demonstrated a positive correlation between axial and radial rigidity measurements but they have not been compared in patients with a wide range of erectile function. We performed a prospective study in a consecutive series of patients presenting with impotence comparing axial rigidity measured with a tonometer and radial rigidity measured by RigiScan. Erectile rigidity also was evaluated by a trained, blinded observer. Overall, RigiScan base and tip radial rigidity correlated well with axial rigidity (p < 0.002) and observer ratings (p < 0.003); axial rigidity similarly correlated well with observer ratings (p < 0.0001). However, when RigiScan base and tip radial rigidity exceeded 60% of maximum, there was a poor correlation with axial rigidity and observer ratings (p > 0.1). In this range, the RigiScan failed to discriminate axial rigidities between 450 and 900 gm. buckling force; however, axial rigidity in this same range again correlated well with observer ratings (p < 0.0001). Since an axial rigidity of more than 550 gm. is considered adequate for vaginal penetration, the RigiScan may not be able to detect mild abnormalities in erectile function. Further study is in progress to evaluate the significance of these findings but presently a RigiScan measurement of radial rigidity in excess of 60% of maximum should be interpreted cautiously and not necessarily regarded as normal. In this range further measurements of axial rigidity or observer ratings of rigidity may be necessary to establish the diagnosis. PMID- 8479012 TI - Predictive value of real-time RigiScan monitoring for the etiology of organogenic impotence. AB - We performed routine diagnostic evaluations in 160 consecutive patients from our impotence clinic. After the diagnostic studies were completed, the results of RigiScan* monitoring during visual sexual stimulation before and after intracavernous injection of vasoactive drugs were compared to the results of standardized pharmacological testing, single potential analysis of cavernous electrical activity and pharmacocavernosometry. The results suggest RigiScan monitoring to be a highly accurate method to evaluate and document objectively the erectile response after intracavernous injection of vasoactive drugs. Although pathological monitoring after intracavernous injection is significantly associated with pathological findings in the specific evaluation, the predictive value of RigiScan monitoring for specific organogenic etiologies is not satisfactory, since normal monitoring showed no convincing correlation to single potential analysis of cavernous electrical activity or cavernosometry. PMID- 8479013 TI - Posttraumatic impotence: magnetic resonance imaging and duplex ultrasound in diagnosis and management. AB - In 15 patients, impotent as a result of prostatomembranous urethral disruption consequent to pelvic crush injuries, magnetic resonance imaging (MRI) and duplex ultrasound were used to establish anatomical and pathophysiological criteria for accurate diagnosis and appropriate management. All patients were initially treated by suprapubic cystostomy diversion for at least 3 months, after which urethral reconstruction was performed. All men were potent before the pelvic trauma, with loss of sexual function immediately thereafter. Preoperative MRI demonstrated prostatic displacement in 13 cases (86.7%) and cavernous injury in 12 (80%). Duplex ultrasound revealed the cause of erectile failure as vasculogenic in 12 patients (80%) and neurogenic in 3 (20%). Treatment of impotence was deferred for at least 18 months after injury. Of the neurogenic group 2 patients were started on intracavernous injection therapy and 1 refused treatment. Of the vasculogenic group 3 patients underwent successful revascularization, 2 are on injection therapy and 1 had a penile prosthesis inserted. The detailed anatomical information obtainable with pelvic MRI and the functional data provided by duplex ultrasonography enabled us to identify the individual organic components of posttraumatic impotence and to select effective cause-specific therapy. PMID- 8479014 TI - Evaluation of vasculogenic impotence by monitoring of cavernous oxygen tension. AB - Color coded duplex sonography, regarded as the gold standard in penile vascular evaluation, does not yield data on cavernous oxygenation itself. In addition to using color coded duplex sonography to measure peak flow velocity in cavernous arteries after injection of 20 micrograms. prostaglandin E1 in 34 unselected patients with impotence, we monitored cavernous oxygen tension with oxygen sensitive Eppendorf needle electrode. During flaccidity the mean cavernous oxygen tension of 38 mm. Hg increased to 61 mm. Hg after injection of prostaglandin E1. Peak flow shown with color coded duplex sonography and maximal oxygen tension correlated well in 24 men (71%). However, in 10 men (29%) normal peak flow did not result in a cavernous oxygen tension of greater than 65 mm. Hg, so this might have been isolated cavernous perfusion defects. In contrast, there was no case of impaired arterial inflow and high oxygen tension. Monitoring of cavernous oxygen tension allows for characterization of patients with cavernous perfusion deficiency. This new and simple diagnostic method might help to improve diagnosis and followup after penile vascular surgery. However, more data on patients and controls will be required to define normal ranges. PMID- 8479016 TI - Impotence evaluation. PMID- 8479015 TI - Prostaglandin E1 and the nitric oxide donor linsidomine for erectile failure: a diagnostic comparative study of 40 patients. AB - A total of 40 patients (average age 55.9 years, range 23 to 78 years) with erectile failure was enrolled in a study to compare 1 mg. of the nitric oxide donor linsidomine to 20 micrograms prostaglandin E1 administered for diagnostic purposes. Prostaglandin E1 was considered comparable to linsidomine by 10% of the patients, slightly superior by 15%, moderately superior by 20% and much superior by 55%. No patient rated linsidomine superior to prostaglandin E1. Objective evaluation of erectile response to linsidomine versus prostaglandin E1 by the investigator revealed no response in 7.5% versus 0% of the cases, tumescence in 57.5% versus 17.5%, semirigid erection in 22.5% versus 17.5% and full erection in 12.5% versus 65%, respectively. Duplex sonography after linsidomine and prostaglandin E1 with evaluation of peak flow velocities (centimeters per second) showed that the increase in peak flow velocity after linsidomine was at least a third less than the increase after prostaglandin E1. The appearance after linsidomine often resembled arterial insufficiency, whereas after prostaglandin E1 there was no evidence of arterial insufficiency. The erectile and hemodynamic response to the nitric oxide donor linsidomine was modest compared to that of prostaglandin E1. Therefore, linsidomine is not a genuine alternative to prostaglandin E1 for the diagnosis and treatment of male impotence. PMID- 8479017 TI - The negative pressure device for erectile disorders: when does it fail? AB - Of 74 men with erectile dysfunction who used a vacuum device at home only 20 were satisfied with the erections achieved. The device was offered only to men who had not been helped by sexual counseling, self-injection therapy or venous surgery, and to 8 patients who had had problems with a penile implant. Fibrosis reduces the chances of success with the vacuum device, and only 2 of 14 such patients used it successfully. In all 9 patients with psychogenic impotence the device failed. Although 9 men did achieve erections with the device, they disliked it so much that they did not begin regular use. Our disappointing overall result was probably due to negative patient selection. PMID- 8479019 TI - Followup results of a combination of calcitonin gene-related peptide and prostaglandin E1 in the treatment of erectile dysfunction. AB - Recent human and animal studies have shown a possible role for calcitonin gene related peptide in penile erection and a therapeutic benefit in combination with prostaglandin E1 for autoinjection therapy. The ethical committee approved calcitonin gene-related peptide-prostaglandin E1 combination for cases of nonresponse or cavernous fibrosis to papaverine-phentolamine. Since June 1990, 65 patients (59 nonresponders and 6 with fibrosis) were injected with 5 micrograms. calcitonin gene-related peptide plus 10 micrograms. prostaglandin E1. Of the 59 nonresponders to papaverine-phentolamine 31 and of the 6 patients with fibrosis 5 had full erectile response. Of these 36 patients 2 experienced pain during the pharmacologically induced erection. A total of 39 patients who had had at least 20 autoinjections of calcitonin gene-related peptide plus prostaglandin E1 was available for minimum followup. There were no side effects, such as pain (the 2 patients with pain mentioned previously were not included in the autoinjection therapy group), systemic side effects or (increased) fibrosis. Our results show that a combination of calcitonin gene-related peptide and prostaglandin E1 may be beneficial to the treatment of impotence in carefully selected patients. PMID- 8479018 TI - Intracavernous pharmacotherapy for impotence: selection of appropriate agent and dose. AB - We performed a retrospective analysis of 101 impotent patients using intracavernous self-injections as primary therapy for vasculogenic impotence. A total of 70 patients used an average of 5.58 micrograms prostaglandin E1 (95% confidence interval 4.83 to 6.34 micrograms) as a single agent, and 31 injected 0.40 ml. (95% confidence interval 0.342 to 0.457 ml.) of a combination of papaverine (12 mg./ml.), phentolamine (1 mg./ml.) and prostaglandin E1 (9 micrograms/ml.). We describe the procedure to establish the dosage for home use and discuss the implications of the low dosages relative to previous reports. PMID- 8479020 TI - Long-term results of penile vein ligation for impotence from venous leakage. AB - Between 1986 and 1991, 46 men with organic impotence documented by dynamic pharmacocavernosometry and cavernosography to have venous leakage underwent penile vein ligation. Despite initial improvement in erections allowing normal intercourse in 34 men (74%) within the first 6 months, long-term (more than 12 months) evaluation revealed sustained potency without adjunctive therapy in only 11 (24%). Of the remaining 35 men 6 (13%) progressed to a penile prosthesis, 8 (17%) required intracavernous vasoactive injection therapy and 21 (46%) have not sought further therapy despite continued impotence. Of the 14 patients who had isolated distal leakage 6 (43%) had sustained erectile function while only 5 of the 32 patients (16%) with proximal leakage maintained potency. Associated complications included penile shortening in 20 (43%) and penile hypoesthesia in 9 men (20%). Therefore, we conclude that the long-term success of penile vein ligation is poor, with only 24% of the patients able to have normal intercourse more than 1 year later, although those patients with distal penile shaft leakage appear to have a greater chance of success than those with more proximal leakage. PMID- 8479021 TI - The Hydroflex penile prosthesis: a test case for the introduction of new urological technology. AB - The AMS Hydroflex* penile prosthesis was introduced for commercial distribution in 1985 but 5 years later this device was no longer available on the United States market. In an attempt to understand why this device, which initially enjoyed substantial popularity, was abruptly withdrawn from the market, patients who underwent implantation at the University of Wisconsin were interviewed and a critical analysis of the Food and Drug Administration approval process of medical devices was performed. An AMS Hydroflex penile prosthesis was implanted in 17 patients (mean age 57.7 years, range 27 to 84 years). The followup period ranged from 37 to 73 months with a mean of 58 months, and 3 patients died within that time. Of the remaining patients 10 (71%) were satisfied with the device in the first months after implantation but only 6 (43%) were satisfied at the time of followup, 9 (64%) were more satisfied with sexual relationships after receiving the prosthesis and 7 (50%) found the prosthesis simple to operate. Mechanical failure was noticed by 11 patients (79%), of whom 5 (45%) underwent further surgery. Classification of medical devices started with the enactment of the Medical Device Amendment to the Federal Food, Drug and Cosmetic Act, May 28, 1976. All medical devices that were in commercial distribution at that time were classified in 3 regulatory control categories depending upon the degree of regulation necessary to assure safety and effectiveness of each device. Before May 28, 1976 no approved application was necessary for marketing medical devices, and the Food and Drug Administration has variable amounts of information about safety and effectiveness of the different devices marketed prior to that date. Since May 1976 approved applications have been mandated for new or significantly changed devices. The specific process by which the Hydroflex prosthesis, as well as other medical devices, is approved is critically reviewed. PMID- 8479022 TI - Analysis of microsurgical penile revascularization results by etiology of impotence. AB - We reviewed the results of microsurgical penile revascularization, with or without a combined procedure to correct cavernosal venous leakage, in 50 consecutive patients with vasculogenic impotence. All patients underwent an extensive preoperative evaluation, including dynamic infusion cavernosography and cavernosometry, and selective penile arteriography. Overall 48% (24 patients) had an excellent postoperative result, 40% (20 patients) were improved and 12% (6 patients) failed, with a median followup of 24 months (range 19 to 56). Furthermore, these results appear durable with no significant difference in length of followup between groups irrespective of surgical outcome (p > 0.05). Analysis of surgical outcomes by preoperative etiology of impotence (pure arterial versus arterial combined with corporeal venous dysfunction) revealed a statistically significant advantage of an excellent surgical outcome in patients with pure arterial impotence compared to those with mixed etiology with results of 67% and 42%, respectively (p < 0.01). There was no significant difference in outcome when patients were analyzed with respect to age or duration of impotence (p > 0.05). We conclude that in patients with arteriogenic impotence identification of concomitant corporeal veno-occlusive dysfunction diagnosed by preoperative dynamic infusion cavernosography and cavernosometry may be helpful, not only in planning a more physiological surgical procedure but also in predicting long-term postoperative success. PMID- 8479023 TI - Impotence therapy. PMID- 8479024 TI - Development of Peyronie's disease with the use of a vacuum constriction device. AB - Vacuum constriction devices are generally considered to be a safe, effective, noninvasive means of producing erections in impotent men. However, long-term study of the effect of subatmospheric pressure on penile structures and vasculature has not been performed. We report the development of Peyronie's disease in a patient after 4 years of complication-free vacuum constriction device use. PMID- 8479025 TI - Pulmonary migration of coils inserted for treatment of erectile dysfunction caused by venous leakage. AB - Embolization of penile veins by coils and/or detachable balloons has been reported as a possible effective form of treatment of venogenic erectile dysfunction. The major appeal for this avenue of therapy in these patients is the reported low morbidity and negligible rate of complications compared to an open operation. We describe a case of asymptomatic pulmonary migration of a coil placed for venous leakage in a patient in whom the procedure was conducted through the femoral vein rather than the deep dorsal vein. We conclude that patients undergoing coil embolization for venous leakage should be appraised of the potential for coil migration. PMID- 8479026 TI - Results of combined Nesbit penile plication with plaque incision and placement of Dacron patch in patients with severe Peyronie's disease. AB - We treated 9 men with severe curvature of the penis secondary to Peyronie's disease with penile plication and a previously unreported technique of incision of the Peyronie plaque and placement of Dacron patch. All men were potent before penile straightening. At a mean followup of 17.5 months all men achieved good to excellent correction of the deformity and they have remained potent. One patient initially complained of numbness of the glans penis and decreased penile rigidity distal to the Dacron patch but potency returned and the numbness resolved. PMID- 8479027 TI - Peyronie's plaque: surgical treatment with the carbon dioxide laser and a deep dorsal vein patch graft. AB - We describe a procedure for ablation of Peyronie's plaque using the carbon dioxide laser, which allows one to remove all palpable evidence of plaque while at the same time avoiding the creation of a large defect in the tunica albuginea requiring coverage with a large graft. The plaque is removed by making either a longitudinal or transverse incision in the plaque with a focused carbon dioxide laser beam from a hand held probe, and evaporating the plaque substance from the undersurface by tangentially directing the laser beam. It is possible to remove large dystrophic calcifications from within the plaque and to augment the repair in the area of greatest curvature using the deep dorsal vein as a patch graft. In cases of narrow plaques relaxation incisions and venous patch grafting alone are usually sufficient to correct the deformity. Our experience with 12 patients is summarized and 2 cases are reported in detail to illustrate the versatility of the procedure. PMID- 8479028 TI - Peyronie's disease. PMID- 8479029 TI - The effects of cancer and cancer therapy on male reproductive function. PMID- 8479030 TI - Antigens in capacitated spermatozoa eliciting autoimmune responses. AB - We studied the possible qualitative antigenic differences between native and capacitated spermatozoa pertaining to immunological infertility. Western blot analysis was used to test serum and seminal plasma immunoglobulin G (IgG) from 18 infertile couples with sperm antibodies, and 14 fertile men and 9 fertile women without significant sperm antibodies against native and capacitated spermatozoa from fertile and infertile men. More fertile and infertile subjects had serum and seminal plasma IgG binding to antigens with molecular weights of 34/36, 46, 68, 97, 105, 115, 120, 130, 150 and 190 kDa. in capacitated versus native spermatozoa of all men. Of the other hand, immune reactivity to antigens with molecular weight 22/24, 30, 32, 50, 80, 88/92 and 180 kDa. found in native autoimmune spermatozoa was strongest in infertile couples with sperm antibodies. This reactivity significantly increased against capacitated autoimmune spermatozoa. Native spermatozoa from few fertile men had these antigens but they appeared after capacitation. It seems that certain antigens normally appearing or enhanced after capacitation are already present in native spermatozoa from infertile men, probably due to an inherent aberration or premature capacitation. This might account for the observed enhanced immune responses in infertile couples to sperm antigens from infertile husbands. PMID- 8479031 TI - The correlation between round cells and white blood cells in the semen. AB - It is generally recognized that white blood cells in semen are detrimental to sperm function and fertility. Traditionally, pyospermia has been suspected if greater than 10 round cells per high power field or more than 1 million round cells per ml. were identified in the semen. Since immature germ cells and white blood cells appear as round cells under wet mount light microscopy, the relationship between increased numbers of round cells in semen and true pyospermia was examined. Semen analyses were performed on specimens from 627 infertility patients. The numbers of round cells per high power field and the number of round cells per ml. of semen were recorded. Specimens from 57 patients (9%) persistently demonstrated greater than 10 round cells per high power field or more than 1 million round cells per ml. and they were subjected to immunohistochemical staining against white blood cell surface antigens. Greater than 1 million white blood cells per ml. were identified in only 20 patients (35%) and only 8 samples demonstrated more than 3 million white blood cells per ml. Of the patients with greater than 1 million white blood cells per ml. 65% had motilities of less than 60% compared to 49% of the patients with less than this amount of pyospermia. This difference was not statistically significant. Round cells counted on a per milliliter basis correlated better with results of immunohistochemical staining than did round cells counted on a per high power field basis. These data demonstrate that the majority of patients with excess round cells in the semen do not have pyospermia and, therefore, empiric antibiotic therapy without further testing will likely be unproductive. PMID- 8479032 TI - Transrectal ultrasound in the evaluation of men with low volume azoospermia. AB - The evaluation of the subfertile man has changed with the advent of noninvasive imaging techniques. We used high resolution transrectal ultrasound early in the evaluation of 25 men 24 to 35 years old with probable ductal obstruction represented by azoospermia or severe oligospermia (less than 1 million sperm per cc) and low volume ejaculate. Of these patients 13 were found to have a post testicular obstructive cause including ejaculatory duct obstruction (5), voluminous seminal vesicle dilatation with obstruction (3), seminal vesicle aplasia (2), nonpalpable vas (2) or epididymal obstruction (1). The other 12 men had either a varicocele (8) or testicular failure (4). Except for vasal or epididymal pathology, the other causes of post-testicular azoospermia presented with an ejaculate volume consistently less than 1.0 cc. All 10 patients with low volume and an abnormal ultrasound had normal follicle stimulating hormone levels and testicular biopsy findings. Sonography not only was helpful in establishing the diagnosis but also in determining the distal extent of the obstruction. Transrectal ultrasound is an important noninvasive diagnostic tool that minimizes the need for more invasive studies in the evaluation of azoospermia, particularly when associated with low ejaculate volume. PMID- 8479033 TI - The value of quantitative testicular biopsy and deoxyribonucleic acid flow cytometry in predicting sperm recovery from electrostimulated ejaculates. AB - Spermatogenic abnormalities have been reported in the majority of men following spinal cord injury, and they contribute to the multifactorial etiology of reproductive dysfunction. Thus far, few have studied the seminiferous epithelium in this group of patients by objective criteria. While quantitative micrometry and flow cytometric analysis are accurate and reproducible methods of quantitating spermatogenesis, the latter is simpler and permits needle aspiration for tissue recovery. The objective of this study is to determine the value of quantitative micrometry and flow cytometric analysis as methods of predicting total sperm yield in electrostimulated ejaculates. Incisional testicular biopsy was performed in 12 anejaculatory men, and the tissue specimens were divided for analysis by quantitative micrometry and flow cytometric analysis. Quantitative micrometry consisted of determining the mean tubular wall thickness, mean tubular concentration of the Sertoli cells and mature spermatids in a minimum of 10 round seminiferous tubules per patient. Specimens were prepared for flow cytometric analysis and the deoxyribonucleic acid histogram was analyzed to determine the percentage of cells in each ploidy compartment. Of the quantitative micrometry parameters analyzed a significant correlation resulted between the total sperm yield per electroejaculate and the mean tubular concentration of late spermatids (p = 0.001) as well as with the mean tubular ratio of late spermatids to Sertoli cells (p = 0.003). The tubular concentration of spermatids resulted in a sensitivity and specificity of 100% and 75%, respectively, to predict adequate sperm yield in semen. Likewise, the mean tubular ratio of spermatids to Sertoli cells resulted in a sensitivity and specificity of 75% and 87.5%, respectively, in its ability to predict normal sperm yield in the recovered ejaculate. Deoxyribonucleic acid flow cytometry analysis showed a normal haploid compartment in all 6 specimens studied, and each was associated with high numbers of sperm in recovered semen. Quantitative histometric parameters correlate significantly with the total sperm yield obtained in electrostimulated ejaculates and may have a role in the selection of candidates for treatment in reproductive rehabilitation programs. PMID- 8479034 TI - Evaluation and treatment of infertility in spinal cord injured men through rectal probe electroejaculation. AB - A total of 18 men older than 19 years with spinal cord injury was evaluated for fertility potential with testing of semen obtained by rectal probe electroejaculation. After fertility testing, including sperm penetration assay, semen cryopreservation and sperm antibody status, 6 of the 18 men proceeded with their partners to use rectal probe electroejaculation in efforts to conceive. Sperm was obtained in 16 of 18 cases. Average ejaculate total sperm count (306 million) was good but motility (22%) was poor. Adequate sperm retrieval after processing yielded a normal sperm penetration assay in 4 of 16 cases (25%) in which sperm were obtained. Favorable semen cryopreservation (greater than 33% of pre-freeze motility noted after thaw) was present in 5 of 16 cases (31%). Live births were achieved in 2 of 6 couples attempting conception. Despite the typically poor sperm motility noted in electroejaculates, rectal probe electroejaculation can result in pregnancies from couples involving spinal cord injured men. The sperm penetration assay data indicate that pregnancy should be achievable in at least 25% of spinal cord injured couples. Achieving these conceptions requires a team approach involving a urologist/andrologist, gynecologist/reproductive endocrinologist and a sperm-processing laboratory. PMID- 8479035 TI - Infertility diagnosis. PMID- 8479036 TI - Should the testicular artery be preserved at varicocelectomy? AB - A surgical method of varicocelectomy, in which the internal spermatic veins together with the testicular artery are ligated as a whole in the retroperitoneal space, has been proposed as a simple and reliable procedure. We evaluated the effects of ligating the testicular artery at varicocelectomy on fertility. A total of 34 subfertile patients with a left varicocele was randomized into an artery-preserved or artery-ligated group at open varicocelectomy and the change in semen quality was prospectively studied. The artery-preserved group showed improvements in sperm density and total sperm count, while the artery-ligated group showed improvements in sperm density, total sperm count and sperm motility. The results indicated identical improvement in semen quality in both groups of patients. Testicular volume, measured by a punched-out orchidometer, did not change in any of the patients in the ligated group, except for 1 with a grade 3 varicocele, although this decrease could not be detected by sonography. The effects of artery-preserving and artery-ligating varicocelectomy on postoperative pregnancy rates were investigated by examining 116 patients retrospectively. The pregnancy rates of 37.8% and 23.8% in the artery-preserved and artery-ligated groups, respectively, were not significantly different. Despite the theoretical advantage of artery preservation, our study did not show any significant difference between artery-preserving varicocelectomy and the artery-ligating operation when improvements in semen quality and postoperative pregnancy rate were evaluated. PMID- 8479037 TI - Varicocele vein ligation in 565 patients under local anesthesia: a long-term review of technique, results and complications in light of proposed management by laparoscopy. AB - Several recent reports have suggested that laparoscopic internal spermatic vein ligation provides a simpler, less debilitating and more cost efficient method of varicocele ligation than conventional surgical techniques. We analyzed the results of open varicocele ligation using local anesthesia in 565 patients for 10 years. All surgery was performed in the outpatient setting using 0.5% lidocaine. In most patients 50 to 200 mcg. fentanyl or 3 to 7 mg. midazolam were used for intravenous sedation. The average operating time, including the administration of anesthesia, was 39 minutes for unilateral and 71 minutes for bilateral procedures. All patients returned to light duty work in 24 to 48 hours and full strenuous physical activity within 1 week. The only complications encountered were 2 wound hematomas (0.3%), 4 minor wound separations (0.7%) and 41 hydroceles (7.3%). Semen improvement and pregnancy rates were similar to those reported in prior series. This study demonstrates that varicocele vein ligation can be done rapidly, efficiently and safely using local anesthesia with time of recovery and return to work comparable to those reported for laparoscopic techniques. PMID- 8479038 TI - Microsurgical epididymovasostomy: predictors of success. AB - The results of microsurgical epididymovasostomy for congenital and acquired vasoepididymal obstruction were retrospectively reviewed in 22 patients in an attempt to determine what preoperative or intraoperative factors might predict surgical success. The overall success rate, defined as sperm on postoperative semen analysis, was 48%. The presence of sperm on an intraoperative touch preparation from the epididymis was significantly correlated with response (chi square 3.24, p < 0.10) and no patient without sperm on touch preparation had sperm on subsequent semen analyses. Testicular biopsy positive for spermatogenesis and presence of motile sperm on intraoperative touch preparation were not statistically significant predictors of response. These results suggest that presence or absence of sperm on intraoperative touch preparation is the only significant prognosticator of successful microsurgical epididymovasostomy. PMID- 8479039 TI - Microsurgical aspiration of sperm from the epididymis: a mobile program. AB - We report data from 25 microsurgical aspirations of the epididymis on 22 men. There were 14 men with congenital absence of the vas, 6 with failed vasoepididymostomy, 1 with adult cystic fibrosis and 1 with a childhood hernia repair. The specimens were used for assisted reproductive technologies, including in vitro fertilization and tubal embryo transfer. The protocol for aspiration, ovulation induction and sperm processing evolved during the course of these studies, and the patients were classified into 2 groups on the basis of methodology. Seventeen procedures were performed for the in-house in vitro fertilization team but 8 other procedures were done for nearby in vitro fertilization centers, and the final prepared sperm samples were transported as part of our mobile program. Group 1 patients underwent standard aspiration techniques, standard ovulation induction and sperm processing by wash and swim up. Among this group there were no fertilizations or pregnancies with 8 in-house and 2 transported specimens. Group 2 patients had leuprolide suppression before ovulation induction, direct intratubular aspiration and a complex sperm preparation, including pentoxifylline stimulation, mini-Percoll filtration and incubation with human follicular fluid. Among this group there were 2 fertilizations and 1 pregnancy with 9 in-house cases, and 3 fertilizations and 2 pregnancies with 6 transported specimens. These results suggest that a mobile program for microsurgical aspirations of sperm from the epididymis and in vitro fertilization or tubal embryo transfer is feasible within the framework of a strict protocol. PMID- 8479040 TI - Surgical therapy of male infertility. PMID- 8479041 TI - Long-term care for older Americans: the institutionalization of senescence. PMID- 8479042 TI - Demographers ponder the aging of the aged and await unprecedented looming elder boom. PMID- 8479043 TI - Bang more of a whimper, health economist avers. PMID- 8479044 TI - Older people now more able-bodied than before. PMID- 8479045 TI - Long-term care training, research expanding. PMID- 8479046 TI - Nursing home research focus on outcomes may mean playing catch-up with regulation. PMID- 8479047 TI - Cross-national comparisons of long-term care become a gold mine for rigorous investigators. PMID- 8479048 TI - In or out of nursing homes, elder care's costly. PMID- 8479049 TI - Adult day care centers vital, many more needed. PMID- 8479050 TI - Must older Americans save up to spend down? PMID- 8479051 TI - Insurance--private and public--a payment puzzle. PMID- 8479052 TI - After long delay, federal regulations for enforcing nursing home standards may be issued this year. PMID- 8479053 TI - Base closings alter military long-term care. PMID- 8479055 TI - From the Centers for Disease Control and Prevention. Rates of cesarean delivery- United States, 1991. PMID- 8479054 TI - From the Centers for Disease Control and Prevention. FDA approval of use of a new Haemophilus b conjugate vaccine and a combined diphtheria-tetanus-pertussis and Haemophilus b conjugate vaccine for infants and children. PMID- 8479056 TI - Information technology and patient care: who, when and why. PMID- 8479057 TI - Information technology and patient care: who, when, and why? PMID- 8479058 TI - Asking about domestic violence: SAFE questions. PMID- 8479059 TI - Alternatives for health care workers with latex glove allergies. PMID- 8479060 TI - Treatment of attention-deficit hyperactivity disorder. PMID- 8479061 TI - Treatment of attention-deficit hyperactivity disorder. PMID- 8479062 TI - Effect of magnesium on postoperative dysrhythmias. PMID- 8479063 TI - Detection and significance of myocardial ischemia in stable patients after recovery from an acute coronary event. Multicenter Myocardial Ischemia Research Group. AB - OBJECTIVE: To determine the clinical significance of silent and symptomatic myocardial ischemia detected by noninvasive testing in stable postcoronary patients. DESIGN: Cohort study with a mean 23-month follow-up. SETTING: Ambulatory outpatients after recent hospitalization for an acute coronary event. PATIENTS: Nine hundred thirty-six patients (76% male; mean age, 58 years) who were clinically stable 1 to 6 months after hospitalization for acute myocardial infarction or unstable angina. INTERVENTIONS: Noninvasive testing involved rest, ambulatory, and exercise electrocardiograms and stress thallium-201 scintigraphy. MAIN OUTCOME MEASURES: Cox regression analysis was used to evaluate the risk (hazard ratio) of first recurrent primary events (cardiac death, nonfatal infarction, or unstable angina) or restricted events (cardiac death or nonfatal infarction) associated with ischemic noninvasive test results. RESULTS: ST segment depression on the rest electrocardiogram was the only noninvasive test variable that identified a significantly increased risk (P = .05) for first recurrent primary events (hazard ratio; 95% confidence limits): rest electrocardiogram ST depression (1.5; 1.00, 2.25); ambulatory electrocardiogram ST depression (0.86; 0.49, 1.51); exercise electrocardiogram ST depression (1.13; 0.82, 1.56); and stress thallium-201 reversible defects (1.3; 0.96, 1.74). Test results were similar for first recurrent restricted events, and in patients with and without angina. Significantly increased risk (P < .05) was noted when exercise-induced ST depression occurred in patients who also had reduced exercise duration (hazard ratio, 3.4) or when reversible thallium-201 defects occurred in patients who also had increased lung uptake (hazard ratio, 2.8). Each high-risk subset made up less than 3% of the population and contained less than 6% of patients with first primary events. CONCLUSION: Detection of silent or symptomatic myocardial ischemia by non-invasive testing in stable patients 1 to 6 months after an acute coronary event is not useful in identifying patients at increased risk for subsequent coronary events. PMID- 8479064 TI - Population-based norms for the Mini-Mental State Examination by age and educational level. AB - OBJECTIVE: To report the distribution of Mini-Mental State Examination (MMSE) scores by age and educational level. DESIGN: National Institute of Mental Health Epidemiologic Catchment Area Program surveys conducted between 1980 and 1984. SETTING: Community populations in New Haven, Conn; Baltimore, Md; St Louis, Mo; Durham, NC; and Los Angeles, Calif. PARTICIPANTS: A total of 18,056 adult participants selected by probability sampling within census tracts and households. MAIN OUTCOME MEASURES: Summary scores for the MMSE are given in the form of mean, median, and percentile distributions specific for age and educational level. RESULTS: The MMSE scores were related to both age and educational level. There was an inverse relationship between MMSE scores and age, ranging from a median of 29 for those 18 to 24 years of age, to 25 for individuals 80 years of age and older. The median MMSE score was 29 for individuals with at least 9 years of schooling, 26 for those with 5 to 8 years of schooling, and 22 for those with 0 to 4 years of schooling. CONCLUSIONS: Cognitive performance as measured by the MMSE varies within the population by age and education. The cause of this variation has yet to be determined. Mini-Mental State Examination scores should be used to identify current cognitive difficulties and not to make formal diagnoses. The results presented should prove to be useful to clinicians who wish to compare an individual patient's MMSE scores with a population reference group and to researchers making plans for new studies in which cognitive status is a variable of interest. PMID- 8479065 TI - Effect of gender on long-term outcome of angina pectoris and myocardial infarction/sudden unexpected death. AB - OBJECTIVE: To determine the effects of female gender on long-term survival and subsequent coronary heart disease events in a population developing first clinical manifestations of coronary artery disease. DESIGN: Follow-up of all Rochester, Minn, residents first diagnosed with either angina pectoris or myocardial infarction/sudden unexpected death between January 1, 1960, and December 31, 1979. MAIN OUTCOME MEASURES: Patients with angina pectoris were followed up through 1982 for survival and time to initial myocardial infarction/cardiac death. Patients with myocardial infarction were followed up through 1982 for survival and time to recurrent myocardial infarction/cardiac death. RESULTS: Angina pectoris was the initial diagnosis for 529 women and 504 men. Myocardial infarction or sudden unexpected death was the initial diagnosis for 611 women and 997 men. The average age of patients diagnosed with angina pectoris was 67.0 years (SE, 0.5 years) for women and 60.0 years (SE, 0.5 years) for men. The average age of patients diagnosed with myocardial infarction/sudden unexpected death was 71.9 years (SE, 0.5 years) for women and 62.0 years (SE, 0.4 years) for men. Women presenting with angina pectoris survived significantly longer and had a lower incidence of subsequent myocardial infarction/cardiac death compared with men of similar age (P < .01). When rates of myocardial infarction and sudden unexpected death were combined to assess all cardiac endpoints with objective criteria ("hard" endpoints), women presenting with myocardial infarction/sudden unexpected death had survival rates and risk of subsequent myocardial infarction/coronary death that were similar to men of the same age. When survival following myocardial infarction was analyzed separately, survival also did not vary by gender. CONCLUSION: In this population, women with angina pectoris as an initial diagnosis, but not those with myocardial infarction or sudden unexpected death, have longer survival and lower risk of subsequent myocardial infarction/cardiac death than do men with the same presentation and of a similar age. PMID- 8479067 TI - Disposal of low-level radioactive waste. Problems and implications for physicians. PMID- 8479066 TI - The appropriateness of hysterectomy. A comparison of care in seven health plans. Health Maintenance Organization Quality of Care Consortium. AB - OBJECTIVE: To develop and test a method for comparing the appropriateness of hysterectomy use in different health plans. DESIGN: Retrospective cohort study. SETTING: Seven managed care organizations. PATIENTS: Random sample of all nonemergency, non-oncological hysterectomies performed in the seven managed care organizations over a 1-year period. Patients who were not continuously enrolled in a plan for 2 years prior to their hysterectomy were excluded. MAIN OUTCOME MEASURES: Proportion of women undergoing hysterectomy in each plan for inappropriate clinical reasons according to ratings derived from a panel of managed care physicians. RESULTS: Overall, about 16% of women underwent hysterectomy for reasons judged to be clinically inappropriate. Only one plan had significantly more hysterectomies rated inappropriate compared with the group mean (27%, unadjusted). Adjusting for age and race did not affect the rankings of the plans and had little effect on the numeric results. CONCLUSION: The rates of inappropriate use of hysterectomies are similar to those for other procedures and vary to a small degree among health plans. This information may be useful to purchasers when they consider which health plans to offer their employees. PMID- 8479068 TI - Pulmonary artery catheterization. Can there be an integrated strategy for guideline development and research promotion? AB - OBJECTIVES: To review the evidence regarding indications for pulmonary artery catheterization (PAC) in critically ill patients, and to propose a guideline generating process that would encourage randomized controlled trials of PAC. DATA SOURCES: Computerized and manual search for randomized trials involving PAC as an integral part of the protocol, published as of October 1992. Manual search for guidelines endorsed by specialty societies and/or proposed by expert panels following an explicit group process. DATA SYNTHESIS: Four trials suggest benefit from PAC for pre- or perioperative management of high-risk surgical patients. Two others indicate that PAC for low-risk aortic aneurysm surgery confers no advantages. Use of PAC to guide therapy aimed at improved mixed venous oxygen saturation was beneficial compared with usual care with PAC in two small trials among patients with septic shock and severe trauma. Other PAC indications are either untested or inadequately tested by small trials. Large trials are needed, but trials to date have been impeded by clinicians' uncertainty about PAC and unwillingness to randomize critically ill patients. No published guidelines for PAC have used a formal group process and/or a hierarchical review of evidence to demarcate proven from unproven indications. CONCLUSIONS: We propose a research promoting expert panel on indications for PAC. Aided by a critical literature review, experts would rate case scenarios on the need for routine PAC with or without a specified intervention strategy. Future trials should test indications where there is either consensus about the uncertainty of need for PAC, or interpanelist disagreement owing to inconclusive evidence. This process could facilitate practice guideline development, utilization management, and large trials of PAC and related interventions. PMID- 8479069 TI - Breast cancer. What the Department of Defense should do with its $210 million. PMID- 8479070 TI - Postinfarction risk stratification. Is preventive war winnable? PMID- 8479071 TI - Mini-Mental State Examination. Norms, normals, and numbers. PMID- 8479073 TI - A piece of my mind. Babu. PMID- 8479072 TI - Changing the system. Implications for physicians. PMID- 8479074 TI - [Complications and management of hematopoietic malignancy therapy]. AB - Infection and refractoriness to platelet transfusion, as complications in hematopoietic malignancy therapy, were investigated. The Hanshin Study Group of Hematopoietic Disorders and Infection treated with 3,346 cases of bacterial infection (7.8% sepsis, 71% sepsis suspected, 13.7% respiratory infection) during the past 13 years. A total of 688 strains were detected as causative organisms, 59.2% being gram-negative bacilli and 40.3% gram-positive bacteria. Comparison of the detection rates obtained 10 years ago and those obtained in the last three years showed a decrease from 73.8% to 46.8% for gram-negative bacilli and an increase from 25.1% to 53.2% for gram-positive bacteria. Twenty-eight antibiotics administered singly and nine combinations of two drugs administered concomitantly were assessed. Efficacy rates were 43.9% to 67.2% for single-drug administration and 35.2% to 64.2% for concomitant administration. Notably, some combinations were less effective than single-drug administration. Of 153 cases of fungal infection seen in the last three years, 80% were caused by the genus Candida. Two antifungal drugs were used, with efficacy rates ranging from 45.5% to 70.0%. In 150 patients undergoing frequent transfusion, anti-HLA alloantibody was measured. The positive rate was 32.9%. In 76 subjects receiving leukocyte-depleted platelet transfusion using a polyester filter, a decreased alloantibody positive rate of 17.1% was obtained. PMID- 8479075 TI - [Recent advances in molecular cytogenetics of leukemia]. AB - Recent advances in molecular cytogenetics of leukemia is reported with special reference to the pathogenesis, diagnosis, prognosis, and potential gene therapy. Regarding leukemogenesis, we found that neocarzinostatin induced a variety of deletions and reciprocal translocations. Among these random chromosome abnormalities, two reciprocal translocations which were specific for certain leukemias could be observed; t(11;14)(q13;q32) and t(7;11)(p15p13). This fact suggests that a translocation carrying oncogene rearrangement may be of potential relevance to the leukemogenesis. The success in making a subgroup (FAB classification) identified a number of subtype-specific translocations in leukemias. It has been suggested that an initiation or progression-associated event is mediated through a gross chromosomal change. The molecular characterization of chromosomal rearrangement leads to the identification of genes involved in leukemia. Our recent works in molecular cytogenetics of chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), FAB-M3 and -M4 were shown in this article. Since rearrangement of relevant genes were cloned, PCR made it feasible to detect minimal residual disease at 10(-6) level after intensive treatment or bone marrow transplantation for CML, Ph-positive ALL, M3 and approximately half of childhood leukemia. Recently developed fluorescent in situ hybridization (FISH) using specific probes can visualize certain chromosomes or chromosomal segments. Ph translocation, for instance, is now demonstrated as three spot-signals in interphase nuclei using YAC (yeast artificial chromosome) BCR clone. Lastly, the use of antisense oligonucleotides for the BCR-ABL junctions should result in the inhibition of growth of CML clone. The strategy using antisense molecules may be very powerful tool in the gene-targeting therapy for human neoplasms. PMID- 8479076 TI - [Ferrokinetics and bone marrow scanning in patients with myelodysplastic syndrome, hypoplastic myelodysplastic syndrome and aplastic anemia]. AB - Ferrokinetic measurement were performed in a total of 48 patients with myelodysplastic syndrome (MDS), 13 with hypoplastic MDS and 25 with aplastic anemia (AA). Forty seven % of patients with hypoplastic MDS progressed to acute leukemia, however none of the patients with AA progressed to acute leukemia. Sixty-nine% of the patients with MDS showed increased erythron transferrin uptake (ETU) caused by ineffective erythropoiesis. On the other hand, 85% of the patients with hypoplastic MDS and all patients with AA showed decreased ETU caused by reduced erythropoiesis. Positive correlation was observed between ETU and the erythroid precursor cells in the bone marrow. Bone marrow scintigraphy utilizing 99mTc-sulphur colloid showed peripheral expansion of active marrow in MDS patients and islands-like distribution in hypoplastic MDS and AA patients. Ferrokinetics and bone marrow scintigraphy demonstrated the difference between typical MDS and hypoplastic MDS. Hypoplastic MDS appears to be a distinct clinicopathologic entity. PMID- 8479077 TI - [Clinical implications of chromosome analysis in myelodysplastic syndrome]. AB - We attempted to identify the cytogenetic significance in predicting the prognosis of patients with myelodysplastic syndrome (MDS). From the results, we established scoring system (Bournemouth scoring+cytogenetic scoring: 3 for > or = 3 chromosomal abnormalities; 1 for -7/7q-, +8, 2 abnormalities); patients with score of > or = 5 had significant worse prognosis than that with score 0-2. Moreover, RARS with complex abnormalities consists of specific subtype showing a high leukemic rate with a high mortality rate. MDS with hypocellular marrow showed prognosis similar to those with typical MDS, while those with minimal dysplasia had prognosis similar to those with aplastic anemia. Patients with MDS were categorized into 3 subtypes, i.e., early disease-evolution, late disease evolution, and no disease-evolution group. About 50% of patients with complex abnormalities showed early disease-evolution, while the remaining died before disease-evolution. In patients showing late disease-evolution, no cytogenetic factor are informative to predict the timing of disease-evolution, except percentage of marrow blasts at the diagnosis. PMID- 8479078 TI - [Treatment of myelodysplastic syndromes with cytokines]. AB - To evaluate the effects of colony-stimulating factors (CSFs) on pathological cells from myelodysplastic syndromes (MDS), CD34-positive cell fractions (mainly blast cells) from nineteen MDS patients and four normal volunteers were successfully enriched by the use of immunomagnetic beads, and their responsiveness to CSFs was examined in short-term liquid suspension cultures. Considerable parts of blast cells from MDS patients remained immature as compared with the favorable maturation of normal blast cells, especially in high-risk MDS group that included two prominent cases with a remarkable blast cell growth without maturation induction by CSFs. Short-term clinical administrations of G CSF often brought about hematological improvements on MDS patients. Other cytokines are also reported to be of use on some patients. However, a few cases progressed to overt leukemia in relation to G-CSF treatment. Much care should be taken with in vivo application of CSFs to high-risk MDS patients, although there may be no effective clue to foresee the risk of leukemic transformation yet. PMID- 8479079 TI - [Bone marrow transplantation for refractory anemia]. AB - Each nineteen patients with severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) have been treated by allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine between 1980 and 1991. Rejection was one of the major problems for SAA patients. Conditioning regimen including irradiation reduced the rejection rate, but secondary cancers may develop as the dose of irradiation increased. It is practically important to determine the indication of BMT for MDS-refractory anemia (RA). We considered the indication of BMT for those who have abnormal karyotypes and/or life threatening complications. Five out of nine patients with MDS-RA are surviving after BMT. Four out of ten cases with MDS RAEB-T and overt leukemia are alive. BMT should be recommended for patients with MDS who satisfy the above conditions, if suitable donors are available. However, it remains to be determined whether the patients with RAEB or MDS overt leukemia should be treated with chemotherapy prior to the preconditioning for BMT. PMID- 8479080 TI - [Levels of serum lactate dehydrogenase and its isozymes with relation to clinical features of pneumocystis carinii pneumonia in acquired immunodeficiency syndrome patients]. AB - The clinical courses of 9 patients with acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis carinii pneumonia (PCP) were followed to investigate the clinical significance of the measurement of various parameters such as serum lactate dehydrogenase (LDH). The mean duration of symptoms before diagnosis was 20 days, and the median duration of therapy was 29.5 days. Serum LDH activity increased in 8 of 9 cases. The isozyme pattern in all cases was characterized by high LDH3 values from the early stage. However, inflammatory markers did not increase in most cases. There were good correlations between the levels of LDH, clinical course, and PaO2. PMID- 8479081 TI - [Leukemic B-cell colony formation in patients with B-cell prolymphocytic leukemia]. AB - We performed in vitro B cell colony assay after coculture with phytohemagglutinin P (PHA-P) and some cytokines (IL-2, IL-4, IL-6 and PHA-MTCM) in B leukemic cells from B-PLL and B-CLL patients. The number of colonies generated with PHA and PHA MTCM was significantly smaller in patients with B-PLL than B-CLL. The surface markers of colony cells from a PLL patient were similar to those of circulating leukemic cells of the patient. IL-2, IL-4 and IL-6 did not enhance PHA-induced B cell colony formation in B-PLL. The expression of CD23 and CD25 antigens of the PLL cells was not enhanced after coculture with PHA for 72 hours in contrast to the enhancement of these antigens in B-CLL. B-PLL cells might be less responsive to PHA than B-CLL cells. PMID- 8479082 TI - [Treatment of adult acute lymphoblastic leukemia with DCVP-l-asp protocol]. AB - From 1985 to 1991, 20 patients with adult acute lymphoblastic leukemia (ALL) were treated with the DCVP-l-asp protocol, which consists of daunorubicin, cytosine arabinoside, vincristine, prednisolone, and I-asparaginase. of these 17 patients (85%) achieved complete remission. A Kaplan-Meier analysis predicted that 30% of the patients in remission would remain disease-free at 5 years. Four patients relapsed between 1 and 2.5 years from the start of treatment. The median survival time for the four patients with an abnormal karyotype was 15 months. No meningeal relapses occurred in patients treated with regular CNS prophylaxis. Myelosuppression was severe, but was well tolerated with supportive therapy, and there were no treatment-related deaths. We conclude that DCVP-l-asp is a feasible and effective protocol for adult ALLs including elderly patients. However, new treatment modalities, such as bone marrow transplantation, should be explored in patients with unfavorable prognostic factors. PMID- 8479083 TI - [Clinical significance of micromegakaryocytes in de novo AML]. AB - Bone marrow specimens obtained from 54 patients with de novo AML and 7 patients with AML evolving from MDS were retrospectively examined for the presence of micromegakaryocytes defined as cells of less than 30 microns in diameter with one or two nuclei. At least 25 megakaryocytes were counted in each patient. Micromegakaryocytes were found in 17 cases (31%), M1:1/11, M2:5/18, M3:0/4, M4:5/12, M5:1/4, M6:4/4, M7:1/1. The median age of the patients was higher in de novo AML with micromegakaryocytes (57 years) than in de novo AML without micromegakaryocytes (41 years) (p = 0.014). Chromosomal analysis revealed that deletion of 5 or 5q-, 7 or 7q- was recognized only in the group of de novo AML with micromegakaryocytes and that t(15;17), t(8:21) and inv (16) were not recognized in this group. Micromegakaryocytes were identified in each bone marrow specimen obtained from 9 of 10 patients with de novo AML with trilineage myelodysplasia. The complete remission rate was significantly lower in de novo AML with micromegakaryocytes (33%) than in de novo AML without micromegakaryocytes (86%) (p = 0.001). The duration of survival of the patients with de novo AML with micromegakaryocytes was shown to be shorter than that of the patients with de novo AML without micromegakaryocytes (p = 0.017). Micromegakaryocytes were recognized in all of 7 patients with AML evolving from MDS. The presence of micromegakaryocytes in bone marrow of the patients with AML indicates a subset of AML with poor prognosis that may be closely associated with myelodysplastic syndrome. PMID- 8479084 TI - [Primary malignant lymphoma of the breast characterized by pleural, pericardiac, and central nervous system invasion and leukemic conversion]. AB - A 46-year old married woman was admitted with a tumor in the left breast. Needle biopsy revealed non-Hodgkin's lymphoma. After preoperative irradiation, a standard curative mastectomy was performed. She had been in complete remission for 12 months, but she was readmitted because of dyspnea and pretibial edema. An echocardiogram and X-ray films of the chest revealed pericardial and bilateral pleural effusion. Cytological examination of both aspirated effusion showed many lymphoma cells compatible with the primary lesion. After the disappearance of effusion following 3 courses of VEPA-M regimen, left hemiparesis and left facial nerve palsy suddenly appeared. The number of the cells in the spinal fluid was 1496/microliters and most cells were lymphoma cells. A MRI scan of the brain showed high intensity lesions in the left thalamus and the white matter of the left temporal lobe on T2-weighted images. Two months after the onset of cerebral involvement, leukemic conversion occurred. Cell surface marker and immunoglobulin gene analyses indicated that these cells were of B cell origin. In spite of multidrug chemotherapy she died in 24 months after the onset of the disease. PMID- 8479085 TI - [Successful treatment with combination chemotherapy of BHAC-AMP in a case of acute myelofibrosis developed from myelodysplastic syndrome with multiple chromosomal aberrations]. AB - A 62 year old male patient was previously admitted to another hospital in February 1989 because of palpitation. Peripheral blood examination revealed pancytopenia. Although the number of nucleated cells in the bone marrow aspirate was in the normal range. It contained 2.2% of blastic cells and dysplastic cells. He was diagnosed to be myelodysplastic syndrome with refractory anemia. He subsequently received repeated blood transfusions and other symptomatic treatments as an outpatient until 1990. When he was admitted to our hospital because of severe pancytopenia. The numbers of WBC, RBC, and platelets were 2,000/microliters, 134 x 10(4)/microliters, 2.9 x 10(4)/microliters respectively. Bone marrow aspiration resulted in dry tap, and biopsy at the iliac bone showed remarkable fibrosis with marked decrease of normal hematopoietic cells. Chromosome analysis revealed multiple aberrations such as 47XY, +8, 13q-, 14p+, 48XY, +8, +9, 13q+. The patient was treated with BHAC-AMP combination chemotherapy. After 3 cycles of the therapy, pancytopenia was improved and chromosomal aberration disappeared. This case was considered to be an acute myelofibrosis developed from myelodysplastic syndrome and worth to reporting with a review of literature, because drastic combination chemotherapy was extremely effective. PMID- 8479086 TI - [Acute megakaryoblastic leukemia associated with Sweet's syndrome, including review of the literature]. AB - A case of Sweet syndrome (SS) associated with acute megakaryoblastic leukemia (AMKL) is reported. A 66-year-old male was admitted to Ashikaga Red Cross Hospital because of skin eruption and sore throat. His eruption was tender and erythema-like nature. He developed a spiking fever after admission. CBC revealed pancytopenia, and a bone marrow specimen showed increased megakaryoblasts and fibrosis. These blasts were shown to be CD41-positive by flow cytometric analysis. A diagnosis of AMKL was then made. Skin biopsy revealed infiltration of neutrophils without vasculitis, compatible with SS. Oral administration of prednisolone was begun which improved his skin lesions considerably. He was then treated with low dose Ara-C, which was however ineffective. The blasts increased in the peripheral blood and he died on the 72nd hospital day. There are 37 reported cases of SS associated with acute nonlymphocytic leukemia, and this is the first case report of SS associated with AMKL. PMID- 8479087 TI - [Ph1 positive myeloblastic crisis followed by Ph1 negative, bcr rearrangement positive T lymphoid crisis in a CML case]. AB - A 26 year old Japanese male who had a history of leukocytosis in 1985 and received chemotherapy because of myeloblastic crisis of chronic myelogenous leukemia (CML) from May 1986, was admitted in November 1987. He had lymphadenopathy, lymphoid tumor of paranasal sinus and pleural effusion with marked lymphoid cells infiltration. On admission, laboratory data of peripheral blood and bone marrow revealed remission; lymphoid cells of pleural effusion were positive for CD3, CD4 and CD8. Second induction chemotherapy was performed successfully. After a few months, however, myeloblastic crisis recurred. Intensive chemotherapy ended in failure and he died of renal and heart failure. Chromosome analysis showed Ph1 and additional abnormalities at myeloblastic crisis and normal at T lymphoid crisis, but the same rearrangement of breakpoint cluster region existed in both crisis cells. Therefore we supposed that more than two-step pathogenesis is involved in the development of Ph1 positive or Ph1 negative CML clone of this patient. PMID- 8479088 TI - [Primary Waldenstrom's macroglobulinemia associated with pure red cell aplasia in which Ts/c lymphocytes inhibiting erythroid precursors were detected]. AB - Waldenstrom's macroglobulinemia (WMG) is a malignancy of B lymphocytes manifesting heavy accumulation of monoclonal IgM in the plasma. In about 80% cases of WMG, Normocytic normochronic anemia (NNA) is complicated. A case of WMG complicated with pure red cell aplasia (PRCA) and the results of in vitro CFU-E colony assay of bone marrow mononuclear cells (BMMNC) cultured with the patient's serum and/or peripheral lymphocytes were described. A 59-year-old male was admitted with serum total protein Level of 9.7g/dl and 48.2% of gamma globulin. The diagnosis of WMG was made by monoclonal IgM in immunoelectrophoresis. Severe NNA was initially demonstrated on admission and gradually deteriorated further. Both reticulocytes in peripheral blood and erythroid precursors in bone marrow were markedly decreased. Erythropoietin showed high values in plasma. Complication by PRCA was considered to be present in vitro study of a CFU-E colony formation of BMMNC from a normal volunteer showed significant suppression on addition of the patient's peripheral lymphocytes and adverse enhancement by adding the patient's serum. This inhibition of CFU-E colony formation was most prominent by the addition of suppressor/cytotoxic T lymphocytes (Ts/c) and was dose dependent. This result showed the existence of inhibitory Ts/c against proliferation of allogeneic erythroid precursors. PMID- 8479089 TI - [Red cell fragmentation syndrome after bone marrow transplantation presumed to be caused by cyclosporin A]. AB - Red cell fragmentation syndrome (RCFS) appeared in a 19-year-old female with acute lymphocytic leukemia 30 days after receiving allogenic bone marrow transplantation (BMT) with a conditioning regimen of a high-dose of cytosine arabinoside, cyclophosphamide and total body irradiation. Thirty days after BMT, severe anemia, reticulocytosis and red cell fragmentation were recognized. As RCFS due to cyclosporin A was suspected, CsA therapy was immediately stopped and methotrexate was substituted for CsA. After the discontinuation of CsA, rapid resolution of the hemolysis was observed. When we resumed treatment with CsA, similar hemolysis developed and disappeared again after discontinuation of CsA. Though we considered that RCFS occurred due to CsA, the participation of GVHD and cytomegalovirus might be undeniable. PMID- 8479090 TI - [Interferon-alpha therapy in the myeloproliferative variants of hypereosinophilic syndrome]. AB - Two cases of hypereosinophilic syndrome (HES) that seemed to be myeloproliferative disorders were treated with interferon-alpha (IFN-alpha). Case 1 was a 45-year-old man with HES who was unresponsive to prednisolone. Because Flaum's hematologic grading score was 8 points, he was diagnosed as a myeloproliferative variant of HES. Although his condition was well controlled by hydroxyurea (HU), cardio-pulmonary insufficiency with refractory eosinophilia developed after 4 years. Instead of HU, IFN-alpha dramatically decreased eosinophil counts, and the clinical situation has stabilized since. Case 2 was a 30-year-old man with HES whose grading score was 9 points. IFN-alpha therapy was started when an accelerated phase of neutrophil dominant with chromosomal abnormality (8 trisomy) occurred. However, he died because of no response to IFN alpha and other chemotherapy. In both cases, studies of eosinophil colony formation revealed no excess of eosinophil colony-stimulating factor from their lymphocytes. Flaum's hematologic grading score was useful for the diagnosis of myeloproliferative variants of HES. IFN-alpha successfully induced hematologic remission in one case, and this therapy may be beneficial for these patients as a first line agent. PMID- 8479091 TI - [Myocardial hemorrhage due to high-dose cyclophosphamide treatment in a case of non-Hodgkin's lymphoma]. AB - 43-year-old male with non-Hodgkin's lymphoma which was resistant to standard treatment received high-dose chemotherapy followed by autologous stem cell transplantation. He had a past history of nephrectomy due to renal cell carcinoma. He had received adriamycin at a total dose of 280mg/m2, but had no episode of heart disease. His chest radiograph, electrocardiogram and serum creatinine were within normal ranges at the start of high-dose chemotherapy. He was given 120 mg/kg of cyclophosphamide (CPM) over two days. Serum creatinine levels elevated two days before transplantation, and he felt discomfort of the chest followed by severe arrhythmia. He died of heart failure one day after the transplantation. Postmortem examination revealed diffuse myocardial hemorrhage with degeneration and necrosis of the heart muscle. CPM is one of the useful antitumor alkylating agents for the treatment of malignant neoplasms. Although conventional doses of CPM can be used without adverse cardiac effects, high-dose CPM has been reported to induce cardiotoxicity in a few cases. Patients often develop fatal acute heart failure. For the safe use of high-dose CPM, we must consider about the dosing schedule, early detection of adverse cardiac effects, and patient risk factors. PMID- 8479092 TI - [Diagnosis of pheochromocytoma using 131I-MIBG scintigraphy]. AB - 131I-MIBG scintigraphy was performed on 18 patients with pheochromocytoma and 25 patients with essential hypertension. In comparison of grade of 131I-MIBG accumulation in various organs the heart accumulation of pheochromocytoma group was significantly lower than that of essential hypertension group. And between the positive and false negative accumulation group of pheochromocytoma reverse relationship was observed between the heart and tumor. The results of 131I-MIBG scintigraphy for pheochromocytoma included 78% sensitivity, 100% specificity, and 90% accuracy. False negative accumulation of tumors were shown at 6 lesions in 4 cases. On the bases of CT and operative findings, false negative accumulation was observed not only in very small tumors, but also in large cystic tumors with a small amount of tumor tissue or totally hemorrhagic necrosis within the tumor. PMID- 8479093 TI - [Scintigraphic appearance in stress 201Tl myocardial SPECT of midportion lesion in left anterior descending artery]. AB - Scintigraphic appearance of left anterior descending artery (LAD) lesion in stress 201Tl myocardial SPECT was studied in 43 patients (pts) with midportion lesion in LAD confirmed by coronary angiography. Right margin of ischemic region in the basal short axial image was -36 +/- 17 degrees and left margin was -128 +/ 75 degrees. In 28 pts of 43 pts left margin lied beyond -120 degrees. From the results it was concluded that in most cases basal inferior wall was perfused by septal branches from LAD. In 6 pts with midportion lesion situated proximal to the first diagonal branch and in 12 pts with midportion lesion situated proximal to the second diagonal branch ischemic region in the apical portion was noted at both septum and anterolateral wall. Critical short axial image, in which right margin of ischemic region shifted from plus to minus area, was the 3.2nd short axial image in the former group and the 5.2nd in the latter group (p < 0.01). In 10 pts with midportion lesion situated distal to the large first diagonal branch, ischemic region was noted in septal wall and not in anterolateral wall. It was concluded that right margin of ischemic region in the basal coronal image was the most useful sign for predicting midportion lesion and left margin for dominance between LAD and right coronary artery and that apical anterolateral ischemia was sign for LAD lesion involving diagonal branch. Critical short axial image was useful for determining whether the lesion was situated proximal or distal to the first diagonal branch and whether the lesion was situated proximal to the second diagonal branch. PMID- 8479094 TI - [Evaluation of the clinical usefulness of a new myocardial imaging agent, 99mTc Tetrofosmin (PPN1011)--a report of multicenter phase III clinical trials]. AB - The clinical usefulness of a new myocardial perfusion imaging agent, 99mTc-1,2 bis[bis(2-ethoxyethyl)phosphino]ethane (99mTc-Tetrofosmin, (PPN1011) was evaluated in 355 patients with various heart diseases. Both 1 and 2 day protocols resulted in images that were significantly clearer than those of 201Tl. The absence of significant drug related adverse reaction supported the safety of the agent for clinical use. Regional abnormalities detected by CAG agreed with 99mTc Tetrofosmin SPECT findings in 74% and with 201Tl SPECT in 78% of this study. Eighty-four percent of an abnormalities were detected with 99mTc-Tetrofosmin SPECT, as compared with those detected with 201Tl SPECT (88.4%). The complete concordance ratio between 99mTc-Tetrofosmin and 201Tl images in segmental analysis was 87-89% at rest and stress. Since 99mTc-Tetrofosmin SPECT was judged clinically useful in 93.2% (331/355) of the patients studied, it is concluded that 99mTc-Tetrofosmin is a promising agent for myocardial perfusion imaging. The simple labeling procedure without heating and cooling is suitable for emergency administration. Reconditioning of myocardial perfusion could be evaluated with 99mTc-Tetrofosmin injection before and after interventional therapy. These are additional features of the agent for clinical use. PMID- 8479095 TI - [Influence of cerebellopontine angle tumor on cerebellar circulation--possibility of remote effect to the cerebellum]. AB - Nine cases (4 men and 5 women, ranging in age from 39 to 73 years with a mean age of 51 years) of cerebello-pontine angle tumors were evaluated by cerebral blood flow scintigraphy on the basis of clinico-functional anatomy. In the 4 of 5 cases in which the middle cerebellar peduncle was compressed by the mass, definite hypoperfusion was revealed in the ipsilateral cerebellar hemisphere. On the other hand, in the 3 of 4 cases without compression of the middle cerebellar peduncle, no asymmetric perfusion was seen in either the right or left cerebellar hemisphere. There were neither supratentorial lesions nor signs of increased intracranial pressure in any of the 9 cases. On the vertebral angiograms of the 4 cases with compression of the middle cerebellar peduncle, non-opacification of the ipsilateral anterior inferior cerebellar artery occurred in only one case. There were no definite signs of reduction of cerebellar blood flow in the other 3 cases. The middle cerebellar peduncle is one of the largest bundles of centripetal fibers in the cerebellar hemispheres. Secondary neuronal fibers of the corticopontocerebellar pathway are the most prominent among these fibers. The mass lesion in the cerebellopontine cistern has a tendency to compress the middle cerebellar peduncle and may deactivate the corticopontocerebellar pathway even if it is small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479096 TI - [Semi-quantitative evaluation of cerebral blood flow with modified bull's eye display using 123I-IMP SPECT]. AB - We developed Modified Bull's Eye (MBE) display to demonstrate 123I-IMP SPECT images on a single map. To compare the difference of some SPECT images, we changed the ratio of the occipitofrontal diameter to the temporal diameter of oblique SPECT images and transformed the oblique images to round-shaped images. After circumferential profile analysis (CPA) was performed on the round-shaped oblique images, the data were mapped into a polar representation (MBE display). The severity score, as the index of severity of the perfusion defect, was calculated in the same way as the myocardial SPECT. We selected five slices from the round-shaped SPECT images and divided each slice into 12 areas. The severity of the perfusion defect was scored (0-3 points) visually, and the total score was defined as the "severity points". We compared the severity score with the severity points for 29 patients and six normal male volunteers. The correlation coefficient of the severity score and the severity points was 0.86 (p < 0.001). The MBE display makes it easy to evaluate SPECT images because it is represented on a single map, and it takes no more time to construct than the myocardial bull's eye display. It should be useful display. PMID- 8479097 TI - [The administered activity of radionuclides in nuclear medicine--rational reduction of medical radiation exposure]. AB - A survey of 104 hospitals was conducted to determine the administered activity of radionuclides. Eighty-five hospitals responded, and reported a total of 119,614 examinations in one year. The examinations included: bone scintigraphy, 26.4%; Thallium-201 (201Tl) myocardial scintigraphy, 15.5%; Gallium-67 (67Ga) scintigraphy, 13.3%; N-isopropyl-p-[123I]iodoamphetamine (IMP) brain perfusion scintigraphy, 7.0%. The administered activity was corrected by body weight only for children at more than 80% of the responding hospitals. The number of hospitals that reported over-administration of radionuclide varied according to the type of scintigraphy performed: bone, 76%; inflammatory (67Ga), 93%; myocardial (201Tl), 89.2%; brain (IMP), 8.5%. The administered activity of IMP was closer to the upper limits specified in the Recommendations on Standardization of Radionuclide Imaging by the Japan Radioisotope Association (1987), because IMP is very expensive and is supplied as single vials. The highest average effective dose was for myocardial scintigraphy, the second highest for inflammatory scintigraphy, and the third-highest for bone scintigraphy. In 201Tl and 67Ga scintigraphy, the entire contents of the vial may be administered two days before the expiration date, because the ratio of (true patient administered activity) to (declared patient administered activity) is similar to the ratio of (radioactivity on the day of supply) to (radioactivity on the day of expiration). The factors that influence administered activity are throughput, price of the radionuclide, and whether the radionuclide is sold as a single vial. In order to decrease the effective dose, it is necessary to establish a close cooperation between medical personnel, the makers of radiopharmaceuticals, and manufacturers of gammacameras. PMID- 8479098 TI - [A case of frontal lobe syndrome followed by serial 123I-IMP SPECT]. AB - Single photon emission computed tomography (SPECT) studies with N-isopropyl-p [123I]iodoamphetamine (IMP) were performed in a 58-year-old man with frontal lobe syndrome. He had abulia and personality changes suggesting frontal lobe impairment. Six follow-up SPECT studies were conducted during 18 months from the onset. On the first scan, no abnormal pattern of regional cerebral blood flow (rCBF) was found. On the second scan, a mild reduction of rCBF was observed in bilateral frontal lobes. Through the third to sixth scans, a progressed reduction of rCBF in bilateral frontal lobes was confirmed by a semi-quantitative regions of-interest analysis. Contrarily, abulia was improved, and personality change was not progressed during that period. Magnetic resonance imaging on admission revealed only a small subdural hematoma and high intensity areas in the right frontal lobe, which were resolved at the time of the sixth SPECT scan. It is suggested that rCBF studies by SPECT is not necessary concordant with psychiatric symptoms, and has possible limitations in pathophysiological evaluation for psychiatric disorders. PMID- 8479099 TI - [Clearance of 99mTc-Tetrofosmin from the myocardium and the adjacent organs]. AB - We studied clearance of a new myocardial perfusion imaging agent, 99mTc Tetrofosmin, from the myocardium and the adjacent organs in nine patients. 99mTc Tetrofosmin was injected intravenously at stress and at rest, and SPECT images were obtained 25 min and 120 min later. Anterior view images were also obtained 10 min and 150 min after the injection to compare the myocardial clearance with those from the liver and lung. Clearance from the liver was faster than those from the myocardium and lung. Washout rate calculated with SPECT was higher for the inferior wall than for the anterior wall and lateral wall (p < 0.05 at rest, N.S. at stress). The value was higher at stress in any region than at rest (the anterior wall and lateral wall, p < 0.01; the septum, p < 0.05; the inferior wall, N.S.). Washout rate for the anterior wall was 3.4 +/- 14.0% at rest and 18.0 +/- 10.6% at stress. The rate for the lateral wall was 2.7 +/- 22.5% at rest and 15.8 +/- 7.9% at stress. It was suggested that rapid hepatic clearance and high myocardial washout at stress may be important in determining the period between the injection of 99mTc-Tetrofosmin and the data acquisition for SPECT imaging. PMID- 8479100 TI - [Basic study of CA549, a new tumor marker for breast cancer, and evaluation of its clinical usefulness]. AB - We performed basic and clinical studies of IRMA kits for serum CA549 antigen and examined the immunological correlation between CA549 and CA15-3 antigens. Satisfactory results were obtained in the basic studies of CA549 assays, such as the reproducibility and the dilution test. Many patients with breast cancer had elevated serum CA549 concentrations and significant correlation was observed between serum CA549 and CA15-3 values. Anti-CA549 antibody completely inhibited the binding of 125I-labeled anti-CA15-3 antibody to its antigens. These results suggest that CA549 and CA15-3 antigens have similar immunological characteristics. PMID- 8479101 TI - [Usefulness of electrocardiogram gated 99mTc-methoxy isobutyl isonitrile (MIBI) single photon emission computed tomography for detection of wall motion abnormality of left ventricle]. AB - We evaluated whether the newly developed perfusion imaging agent "99mTc-methoxy isobutyl isonitrile (MIBI)" has a possibility to detect wall motion abnormality of left ventricle. Electrocardiogram (ECG) gated single photon emission computed tomography (SPECT) was performed in 6 patients with myocardial infarction (anterior: 3 and inferior: 3). Apical and basal short axis images were selected from each patient and circumferential analysis was performed on end-diastolic (ED) and end-systolic (ES) images respectively. Count in end-diastole (EDC) and count in end-systole (ESC) were obtained, then % (ESC-EDC) and (ESC-EDC)/EDC were calculated. Wall motion of left ventricle was evaluated by either ultrasonic cardiogram or left ventriculography. Left ventricle was divided into anterior, septal, posterior and lateral areas and then each area was divided into apical and basal segments (finally the heart was divided into 8 segments). Of 48 segments, 33 segments showed normal wall motion and 15 segments showed abnormal wall motion: hypokinesis, akinesis and dyskinesis. % (ESC-EDC) was 74.39 +/- 16.85% in segment of normal wall motion and 33.27 +/- 23.56% in segment of abnormal wall motion (p < 0.001). (ESC-EDC)/EDC was 48.67 +/- 13.35% in segment of normal wall motion and 23.33 +/- 18.83% in segment of abnormal wall motion (p < 0.001). From these data, lower limit of % (ESC-EDC) and (ESC-EDC)/EDC in normal wall motion was defined as 40 and 22 respectively: mean -2SD of normal wall motion. Sensitivity of diagnosis of abnormal wall motion was 73% in % (ESC-EDC) and 60% in (ESC-EDC)/EDC (n.s.). Specificity was 94% and 97% (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479102 TI - [The recent studies of myocardial blood flow and metabolism by using positron emission computed tomography]. AB - Since the application of positron emission computed tomography (PET) for myocardium, the evaluation of myocardial blood flow, glucose metabolism, fatty acid metabolism, oxygen consumption and etc. has been performed. Especially, it has been regarded very important clinically to evaluate myocardial viability from the mismatch of myocardial glucose metabolism and blood flow. Many early myocardial PET studies were qualitative, while recently noninvasive quantitation method without arterial blood sampling has become possible in quantitating myocardial glucose metabolism or myocardial blood flow reserve. We quantitated regional myocardial glucose utilization rates (rMGU) in 114 cases during fasting, oral glucose loading, or insulin clamp to study the relation between rMGU and plasma insulin value or FFA value, the normal rMGU value during each condition and the difference of rMGU among each part of myocardium. And as to the question in which condition of FDG study was appropriate to evaluate myocardial viability, we introduced the opinion of Schelbert for oral glucose loading or insulin injection method and presented our opinion for fasting or mild insulin clamp. PMID- 8479103 TI - Metabolic response to burn injury: nutritional implications. AB - The response to critical illness involves alterations in all aspects of metabolic control, favoring catabolism of stored energy substrates and protein. Glucose production is accelerated, due principally to a chronic elevation in glucagon. Whereas glucose is available at increased rates, the muscle tissue is less responsive than normal to the stimulatory effect of insulin on glucose uptake. Stored triglyceride is also catabolized at a high rate, predominantly due to enhanced adrenergic activity. This causes the release of free fatty acids at a rate well in excess of their requirement for oxidation, leading to a high rate of reesterification and triglyceride transport in plasma. Protein metabolism is characterized by accelerated catabolism that is not balanced by a corresponding increase in synthesis. Whereas the mechanism for this response is not known, peripheral insulin resistance does not appear to be responsible. PMID- 8479104 TI - Problems in assessing the response to therapy on bone metastases in breast cancer: analysis of post-recurrence prognostic factors. AB - The problems of assessment of response to therapy and the factors contributing to the post-recurrence survival period were clinically investigated using 72 patients mostly with evaluable bone metastases. When the various factors involved in the post-recurrence survival period were investigated by Cox multivariate analysis, the results were significant for number of metastatic lymph nodes at initial surgery (p < 0.05) and disease-free period (p < 0.01), while the therapeutic effect on bone metastases made only a marginal contribution (p = 0.06). Imaging of bone metastases required a long time until effects could be assessed, 4 months (1-20 months) for Partial Response (PR) cases and 10 months (2 60 months) for Progressive Disease (PD) cases, with a median of 8 months, but even so, assessment of effect based on imaging techniques did not necessarily correlate with the clinical course. No background factors or therapeutic modalities typical for responders were noted. These findings require a comprehensive assessment of therapeutic utility for bone metastases by considering (a) the improvement of clinical symptoms (b) the decrease in tumor markers, and (c) the absence of new lesions. PMID- 8479105 TI - Changes of pial vessel diameter and CO2 reactivity during insulin-induced hypoglycemia and in the recovery period following glucose administration. AB - The present study examined the changes of cerebrovascular CO2 reactivity during insulin-induced hypoglycemia and in the recovery period following glucose administration in cats. The diameters of pial vessels were continuously measured using the vidicon camera system. Hypoglycemia was induced by intraperitoneal injection of Actrapid insulin (100 IU/kg). Cerebrovascular CO2 reactivity was estimated by the changes of pial vessel diameters during 3 min inhalation of 5% CO2 in air at each stage of glucose level. CO2 reactivity was impaired in the hypoglycemic stage and this impairment was further enhanced in the early recovery stage. In the late recovery stage, CO2 reactivity was restored particularly in the small arteries which were less innervated by autonomic nerves. These results suggest that the sympathetic activity plays an important role in the impairment of cerebrovascular CO2 reactivity during hypoglycemia. PMID- 8479106 TI - A system for three-dimensional shape measurement and its application in microtia ear reconstruction. AB - Microtia is one form of ear anomalies representing the defect of a partial or total loss of external ear. This paper describes new method of total auricular reconstruction which combines the use of tissue expander and the non-contact, 3 dimensional (3-D) shape measurement system. The anterolateral and posterior surface of the both sides of the ear of the patients were measured with the 3-D shape measurement system. The data from normal side was mirror-imaged electronically and transferred to the computer-controlled milling machine to create the life-sized, mirror-image wax model. These models were sterilized and used as a template or an aid during assembling procedure of the autologous cartilage framework in order to reproduce the 3-D configuration of the wax model. Seven cases were treated with this method and 5 cases (72%) were graded as excellent (superior to that result obtainable from conventional methodology), one each (14%) was good (better result) and fair (the same level). There are no poor evaluations. In two cases, the exposure of the expander, one of the major complications, developed. Although additional surgery was needed, excellent and fair result was obtained in these cases. It was concluded that the method presented here was evaluated as an overall good method and its application should be further extended. PMID- 8479107 TI - Lymphangioma of the jejunal mesentery in an adult: a case report and a review of the Japanese literature. AB - A rare case of lymphangioma of the jejunal mesentery in a 34-year-old woman is presented. She was diagnosed as having an ovarian cyst preoperatively, but laparotomy revealed a cystic tumor of the mesentery that was histologically diagnosed as lymphangioma. Thus far, 44 cases of adult mesenteric lymphangioma have been reported in Japan. In nine cases, accurate diagnosis of mesenteric cysts was obtained preoperatively. In 31 cases, complete excision with or without bowel resection was done, whereas two cases were partially resected and one case was drained. PMID- 8479108 TI - Immunoelectron microscopic study on IgA, secretory component and complement component C3 in the liver of children undergoing total parenteral nutrition through neonatal period. AB - To study the mechanism of the intrahepatic cholestasis observed during total parenteral nutrition (TPN) in neonates, we examined the localization of IgA, secretory component (SC) and complement component C3 (C3) in the liver in 4 patients by light and electron microscopic immunohistochemistry. In the patients who received TPN for 1 month, IgA- and SC-positive cholestasis was limited to bile canaliculi, but the integrity of both the canalicular wall and intercellular tight junction was maintained. These findings suggest that obstruction in the biliary tract develops at the canalis of Hering, causing reflux of IgA and SC into the bile canaliculi. When the duration of TPN extended beyond 6 months, the cholestasis in bile canaliculi progressed further, and degeneration of hepatocytes became more marked. Bile retained in hepatocytes occasionally contained IgA and SC. IgA- and SC-positive cholestasis also developed in the interlobular bile ducts, where no cholestasis had been observed 1 month after the beginning of TPN. SC production and SC-mediated transport of IgA, which are important functions of bile duct epithelial cells in the local immune mechanism, were impaired in association with the injury of those cells. C3 was localized not only in the hepatocellular organelles where C3 is normally observed, but also in the lumen of dilated bile canaliculi, suggesting that C3 is released from hepatocytes into bile in neonates receiving TPN and that C3 may be involved in some local immune mechanism of biliary system. PMID- 8479109 TI - [Identification of Mycobacterium avium-intracellulare complex in Tohoku district of Japan by using DNA probes]. AB - Attempts were made to identify Mycobacterium avium and Mycobacterium intracellulare in the M. avium-intracellulare complex (MAC) isolated in the Tohoku district of Japan by using DNA probes (Gen-Probe; Rapid Diagnostic System) which are specific for M. avium, M. intracellulare and M. tuberculosis complex, respectively. In the Tohoku district, the ratio of M. avium isolates (80%) exceeded that of M. intracellulare isolates. It was thus shown that, in the Tohoku district where no data concerning the ratio of M. avium to M. intracellulare isolates had been available, the ratio of M. avium by far exceeded that of M. intracellulare. PMID- 8479110 TI - [Investigation of self-discharged patients of pulmonary tuberculosis]. AB - This study investigates 27 cases in which the patients left hospital care without permission for personal reasons. These patients were classified as "self discharged patients". Each of the patients had been diagnosed as having pulmonary tuberculosis, and were receiving treatment at the National Chiba Higashi Hospital during the period from January 1988 to July 1991. Disease was in an advanced stage in each of the patients when admitted: all sputum examinations were positive and chest roentgenograms revealed cavities in 26 patients. In addition to pulmonary tuberculosis, the patients were also diagnosed has having a variety of other medical complications such as diabetes mellitus, gastric ulcers and liver disease. Many of them were unemployed or were day labors. Reasons attributed to patients self-discharge from the hospital included repetition of alcohol drinking and unauthorized outings. At the time patients chose to leave hospitalization 11 cases checked positive for sputum examinations, and 16 cases never returned to complete therapy. Many of them were rated as high risk patients for pulmonary tuberculosis because they had no immediate family, did not own a residence or have regular employment thus economic and psychological conditions were very low. There is a high possibility that these individuals will suffer pulmonary tuberculosis relapse and become infectious bacteria carriers. It is important that such patients be hospitalized long enough to receive adequate treatment to prevent then from becoming infectious carriers and spreading disease. PMID- 8479111 TI - [Drug resistance of M. tuberculosis and comparison of drug sensitivity test in Nepal]. AB - In Nepal, drug sensitivity test for M. tuberculosis has been carrying out at the clinic of German-Nepal Tuberculosis Project (GENETUP) since 1986 and at National Tuberculosis Centre (NTC) since 1991. The studies of primary drug resistance and acquired drug resistance were performed at NTC. On the other hand, results of drug sensitivity test at GENETUP and NTC were compared and analyzed. In total, 160 M. tuberculosis strains which were isolated from new smear positive patients were studied for the primary drug resistance. One of 160 strains, 21 (13.1%) strains were resistant to one or more drugs. Resistance rate to one drug, two drugs and three drugs were 9.4%, 3.1% and 0.6% respectively. Resistance to four drugs and five drugs were not found. Prevalence of resistance of each drug were INH 8.1%, SM 5.0%, RFP 2.5%, EB 0.6% and Tb1 1.3% respectively. In total, 125 strains which were isolated from previously treated patients were studied for the acquired drug resistance. Out of 125 strains, 103 (82.4%) strains had resistance to one or more drugs. Resistance rate to one drug, two drugs, three drugs, four drugs and five drugs were 13.6%, 28.0%, 31.2%, 4.0% and 5.6% respectively. Resistance rate of each drug were INH 56.8%, SM 38.4%, RFP 71.2%, EB 16.8% and Tb1 24.0% respectively. Since media, criteria of resistance and definition of resistance for drug sensitivity test are different between GENETUP and NTC, it is difficult to compare the results. However, it is necessary to understand the differences well and get good agreement with both sides. PMID- 8479112 TI - [Behaviour of gamma delta TCR+ T cells during the course of nontuberculous mycobacterial infections and proliferative response of host lymphocytes to 65kD heat shock protein]. AB - In order to know the possibility that gamma delta TCR+ T cells induced by Mycobacterium avium complex (MAC) infections participate in the expression of host resistance and in the occurrence of Behcet disease, we examined the behaviour of them in MAC-infected host mice. In both BALB/c (Bcgs; MAC susceptible) and CBA/JN (Bcgr; MAC-resistant) strain mice, a transient but appreciable increase in the number of gamma delta TCR+ T cells in the host peritoneal lymphocytes was noted around week 1 to 2 after M. intracellulare infection via ip. route. The degree of induction of gamma delta TCR+ T cells was somewhat higher in CBA/JN mice than in BALB/c mice. Therefore, gamma delta TCR+ T cells are partly responsible for the expression of host resistance against the MAC in the early phase of infection. However, the subsequent decrease in the level of gamma delta TCR+ T cells was observed by week 5. Thus, in the case of chronic state of MAC infection, the size of gamma delta TCR+ T cell-pool seems to be in normal level. This suggests that per cell activity of gamma delta TCR+ T cells rather than mobilizing number of them is important factor in the mechanisms for occurrence of allergic diseases including Behcet disease. Although, the early increase in gamma delta TCR+ T cells of peritoneal cells was also observed during the course of M. fortuitum infection, the degree of induction of gamma delta TCR+ T cells in A/J mice (M. fortuitum-susceptible) was in similar level as that in BALB/c mice (M. fortuitum-resistant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479113 TI - Parathyroid gland function in chronic renal failure. AB - The concept that the PTH-calcium curve is representative of parathyroid function has been discussed. Comparisons of parathyroid function have been made between normal humans and hemodialysis patients and also between hemodialysis patients with different forms of renal osteodystrophy. From these comparisons, it is apparent that the magnitude of HPT is much greater in patients with renal failure than in normal humans, and as represented by the ratio of basal to maximal PTH, the parathyroid gland appears to be stimulated at basal serum calcium levels in hemodialysis patients. Similarly, based on an analysis of the PTH-calcium curve, we were able to determine that several differences in parathyroid function were present in hemodialysis patients with different forms of renal osteodystrophy. As compared to hemodialysis patients with LTAABD and aplastic bone disease, patients with osteitis fibrosa have a greater magnitude of hyperparathyroidism, a greater sensitivity of the parathyroid cell (slope), a higher set point of calcium, and greater PTH stimulation at basal serum calcium (ratio of basal to maximal PTH). Calcitriol treatment of hemodialysis patients with osteitis fibrosa resulted in a significant decrease in PTH throughout the PTH-calcium curve and also reduced the sensitivity (slope) of the PTH-calcium curve. The concept of hysteresis has been discussed as well as the role that the ambient basal serum calcium concentration may have on the determination of the PTH-calcium curve. Finally, the effect that successful renal transplantation has on HPT has been examined. In conclusion, we believe that the PTH-calcium curve provides a reliable assessment of parathyroid function, and as such, has considerable application for the study of parathyroid disorders in the clinical setting. PMID- 8479114 TI - Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake. AB - This study was designed to test the hypothesis that induction of insulin-like growth factor-1 (IGF-1) is reduced in the uremic rat liver, which would help to explain the purported growth hormone resistance noted in uremia. IGF-1 mRNA, in the steady state and after acute induction by two doses of 100 micrograms/100 g body wt recombinant human growth hormone (rhGH), was quantitated by solution hybridization in total liver RNA, extracted by the guanidine thiocyanate/cesium chloride gradient method. Eighteen Sprague-Dawley rats weighing 100 to 102 g were randomly divided into three groups: sham-operated control rats (control group); 5/6 nephrectomized rats (uremic group); and sham-operated controls with dietary intake matching that of the uremic rats (pair-fed group). The results showed that the steady state liver IGF-1 mRNA was 1.7 arbitrary densitometry units (ADU) in the uremic animals, and was lower than the value of 3.2 ADU in the control animals (P < 0.05). After the acute administration of rhGH, the liver IGF-1 mRNA of control, uremic and pair-fed groups showed mean increases of 154% (P < 0.05), 124% (not significant, NS) and 117% (NS), respectively. The lack of IGF-1 induction in the uremic group supported the concept of growth hormone resistance in uremia. In addition, a similar lack of induction was observed in the pair-fed group, whose food intake was 65% that of the control animals. This indicated that the lack of IGF-1 induction was at least partially due to the reduced food intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479115 TI - IGF-II/Man-6-P receptors in rat kidney: apical localization in proximal tubule cells. AB - The present study was performed to determine the localization of insulin-like growth factor II (IGF-II) binding in the rat nephron and, furthermore, to determine directly the distribution of the IGF-II/Man-6-P receptor in the proximal tubule. The IGF-II/Man-6-P receptor was visualized by immunohisto- and cytochemical techniques, and the binding of IGF-II was shown by light and electron microscope autoradiography applying 125I-IGF-II directly on cryosections. The tubular uptake of IGF-II was studied by autoradiography after in vivo injection of 125I-IGF-II. The light microscope immunolabeling was confined to a relatively narrow band in the apical part of the proximal tubule cells just below the brush border, and was strongest in the first portion of the proximal tubule, segment 1 (S1), with decreasing intensity in segment 2 (S2) and weaker in segment 3 (S3). Several cytoplasmic bodies were labeled but no label was observed in the basolateral part of the cells. We did not detect any labeling of glomeruli or other segments of the nephron. Electron microscope immunocytochemistry in the proximal tubule revealed a strong labeling in apical endocytic invaginations, small endocytic vacuoles, and large endocytic vacuoles, weaker in lysosomes and dense apical tubules. Light microscope autoradiography after incubation of cryosections with labeled IGF-II demonstrated an intense labeling just beneath the brush border, especially in S1 of the proximal tubule, and, in addition, the corresponding electron microscope autoradiography revealed an intense labeling over large endocytic vacuoles and lysosomes. These results were confirmed and extended by competitive binding experiments and quantitative immunocytochemistry. After i.v. injection of 125I-IGF-II autoradiographic grains were almost exclusively observed in the electronmicroscope over endocytic vacuoles and lysosomes in the S1 of the proximal tubule. The present study shows that the IGF-II/Man-6-P receptor is located in components of the vacuolar system in the apical cytoplasm of rat renal proximal convoluted tubule cells, mainly in S1. This localization was seen to be consistent using various immunolabeling and autoradiographic techniques in vivo and in vitro. PMID- 8479116 TI - Calcium antagonists and converting enzyme inhibitors reduce renal injury by different mechanisms. AB - Both glomerular hypertension and hypertrophy have been associated with the development of glomerular injury in models of hypertension and reduced renal mass. The purpose of this study was to examine the effects of antihypertensive therapy on these parameters in the remnant kidney model of progressive glomerular sclerosis. Rats underwent 5/6 nephrectomy and were randomly assigned to receive either no therapy, the calcium entry blocker (CEB), nifedipine, or the angiotensin converting enzyme inhibitor (CEI), enalapril. Administration of either drug was associated with a reduction in systemic blood pressure and in the severity of glomerular injury assessed eight weeks after renal ablation. Micropuncture studies four weeks after ablation revealed that systemic and glomerular capillary pressure were high in untreated remnant kidney rats and reduced by enalapril. Administration of nifedipine was associated with a decline in systemic pressure, however, plasma renin levels increased, causing efferent arteriolar vasoconstriction and persistence of glomerular hypertension. Morphometric analysis showed that kidney weight, glomerular volume and glomerular capillary radius were lower in nifedipine treated rats than in the other two groups, indicating that the CEB, but not enalapril, inhibited the hypertrophic response to ablation of renal mass. Therefore, both CEIs and CEBs reduce glomerular injury in rats with remnant kidneys but they may act by different mechanisms. CEI reduce glomerular capillary pressure while CEBs inhibit compensatory kidney growth. PMID- 8479117 TI - Distribution of erythropoietin producing cells in rat kidneys during hypoxic hypoxia. AB - We have used in situ hybridization to determine the localization and distribution of cells expressing the erythropoietin (EPO) gene in kidneys of rats exposed to reduced oxygen tensions to characterize the control of renal EPO formation during hypoxic hypoxia. Animals were subjected to severe hypoxia (7.5% O2) for 4, 8 and 32 hours to assess changes related to the duration of hypoxic exposure, and additionally to 9% and 11.5% O2 for eight hours to define changes related to the degree of hypoxia. The number of cells containing EPO mRNA were counted on tissue sections and compared to tissue concentrations of EPO mRNA and to the serum hormone concentrations. In situ hybridization revealed expression of the EPO gene exclusively in peritubular cells that were predominantly located in the cortical labyrinth under all conditions tested. After four hours of severe hypoxia (7.5% O2) approximately 170-fold more cells were found to contain EPO mRNA than under normoxic conditions. The number of EPO producing cells did not change significantly between four and eight hours exposure to 7.5% O2, but the amount of EPO mRNA per kidney increased approximately threefold. Further continuation of hypoxia resulted in down-regulation of renal EPO mRNA levels, which was mainly due to a reduction in the number of cells containing EPO mRNA. Comparison of graded degrees of hypoxia applied for eight hours showed an inverse exponential relationship between oxygen tension and the number of EPO producing cells. This recruitment of cells expressing the EPO gene occurred along a gradient extending from the corticomedullary border to the subcapsular tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479118 TI - Lack of albuminuria in the early heterologous phase of anti-GBM nephritis in beige mice. AB - Passive anti-glomerular basement membrane (GBM) nephritis in the mouse is accompanied by acute massive albuminuria in the early heterologous phase. As we have previously shown, this albuminuria does not occur in the beige mutant of the C57BL/6J strain which is deficient for the leukocytic neutral proteinases elastase and cathepsin G. To address the question whether an intrinsic defect in the polymorphonuclear granulocyte (PMN) or local factors in the beige kidney are responsible for the lack of albuminuria in the beige mouse strain, we conducted reciprocal bone marrow transplantations (BMT) in beige and congenic control mice. Injection of anti-GBM antibody resulted in only slight albuminuria (89 +/- 47 micrograms/18 hours; N = 6) in normal (that is, non-irradiated, non reconstituted) beige mice. By contrast, in beige mice, reconstituted with bone marrow (BM) from control mice, acute albuminuria developed (3032 +/- 1408 micrograms/18 hours; N = 8), to a degree comparable to that in non-irradiated control mice (4411 +/- 3405 micrograms/18 hours; N = 6, P < 0.01). Albuminuria in control mice, reconstituted with beige BM, was in the range of the normal beige mice (112 +/- 55 micrograms/18 hours; N = 9). Reconstitution with syngeneic bone marrow demonstrated that BMT by itself did not influence the level of albuminuria. All mice showed similar morphological lesions, with comparable influx of PMN in the glomeruli two hours after antibody injection. Elastase activities of PMN extracts in BMT groups were not different from those in donor mice. We conclude that the absence of albuminuria in beige mice is caused by an intrinsic defect in leukocytic neutral proteinase activity. PMID- 8479119 TI - Ca2+ oscillations in the rabbit renal cortical collecting system induced by Na+ free solutions. AB - The presence of a Na(+)-Ca2+ exchange system has been previously demonstrated at the basolateral side of the cortical collecting system. The role of such an exchanger in maintaining low intracellular [Ca2+] ([Ca2+]i) in this nephron segment is now investigated. Cells from the connecting tubule and cortical collecting duct of rabbit kidneys were isolated by immunodissection with mAb R2G9 and subsequently cultured on glass coverslips. [Ca2+]i was measured in single cells using quantitative fluorescence microscopy. Surprisingly, isoosmotic substitution of extracellular Na+ ([Na+]o) for N-methylglucamine generated [Ca2+]i oscillations in individual cells instead of an anticipated sustained increase in [Ca2+]i. The amplitude of these oscillations ranged between 150 to 600 nM (average 308 +/- 19 nM) and occurred at a frequency of 0.63 +/- 0.03 min 1, with a duration of 44 +/- 2 seconds per spike. Oscillations were only observed in response to [Na+]o less than 5 mM and lasted until Na+o was re-introduced. The compound U73122 (10 microM), a new phospholipase C inhibitor, inhibited [Ca2+]i oscillations, which strongly suggests that IP3 generation initiates [Ca2+]i oscillations. [Ca2+]i oscillations were independent of extracellular Ca2+ and could not be inhibited by lanthanum ions, indicative for an intracellular source for the generation of Ca2+ spikes. Addition of thapsigargin, a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase activity, induced a considerable intracellular Ca2+ release, after which [Ca2+]i oscillations could no longer be provoked. Caffeine (20 mM) reversibly inhibited the Ca2+ oscillations, which implies that Ca(2+)-induced Ca2+ release is involved in generating these oscillations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479120 TI - Vasopressin receptor-mediated endocytosis in cells transfected with V1-type vasopressin receptors. AB - We examined the process of receptor-mediated endocytosis in A-9 lung fibroblast and chinese hamster ovary (CHO) cells transfected with the recently cloned vasopressin V1a receptor (51). We used a fluorescent labeled vasopressin analog (rhodamine-mercaptopropionic acid lysine vasopressin) and radiolabeled vasopressin to examine this process in the two transfected cell lines. Both A-9 and CHO cells internalize vasopressin in a manner consistent with receptor mediated endocytosis. A-9 cells internalize vasopressin more rapidly than CHO cells. The process is inhibited by vasopressin and by specific vasopressin V1 receptor antagonists but not by specific V2 receptor antagonists. Hypertonic sucrose inhibits endocytosis in both cell types suggesting a role of clathrin coated pits in the endocytosis of receptor in these cells. These cells are excellent models in which to examine the effect of receptor mutations on vasopressin receptor-mediated endocytosis. PMID- 8479121 TI - Nonenzymatic glycation of mesangial matrix and prolonged exposure of mesangial matrix to elevated glucose reduces collagen synthesis and proteoglycan charge. AB - Expansion of the mesangial matrix in diabetes occurs after prolonged exposure to the diabetic milieu. To mimic the long-term hyperglycemia of diabetes mellitus we developed tissue culture systems that might approximate the chronic state. This was accomplished in two ways: (1) by growing mesangial cells on extracellular matrix glycated and crosslinked in vitro and (2) by continuously growing cells on their own matrix on filters in elevated glucose medium (500 mg/dl) for up to eight weeks without passage. Synthesis of collagen and proteoglycans was evaluated in cells grown under these conditions. In both these situations, 3H proline incorporation into collagenase sensitive protein and 35S incorporation into sulfated proteins were reduced compared to control cultures. Despite reduction in 35S incorporation into proteoglycans in the high glucose cultures, total glycosaminoglycan content was unchanged. However, proteoglycans generated by mesangial cells grown in elevated glucose media were of a lower negative charge than controls. In mesangial cells continuously grown on filters, the levels of messenger RNA for collagen types I and IV, biglycan and TGF-beta were not different in cells grown at elevated or standard glucose concentrations for two and four weeks. We conclude that crosslinking of mesangial matrix or continuous culture of cells for prolonged periods of time in high glucose medium, which may also crosslink matrix, suppresses collagen synthesis and reduces the negative charges on matrix proteoglycans without altering mRNA levels. PMID- 8479122 TI - Bilateral ureteral obstruction alters levels of the G-protein subunits G alpha s and G alpha q/11. AB - To evaluate the effects of bilateral ureteral obstruction (BUO) on the levels of G-protein subunits in glomeruli, we examined the types and amounts of G-protein subunits in glomerular membranes from sham-operated control (SOC) rats and rats with BUO of 24 hours duration utilizing bacterial toxin-catalyzed ADP ribosylation and specific antibodies. ADP-ribosylation catalyzed by cholera or pertussis toxin demonstrated the presence of Gs and Gi proteins in glomerular membranes. Immunoblots further revealed the existence of two types of G alpha s (45 and 52 kDa), as well as G alpha i2 (40 kDa), G alpha i3 (41 kDa), G alpha q/11 (42 kDa) and G beta (35 to 36 kDa) in glomerular membranes. The predominant subspecies of G alpha s was the 52 kDa protein. Detectable amounts of G alpha o were not found in glomerular membranes. Moreover, G-protein subunits were not detected in cytosolic extracts of glomeruli. Both forms of G alpha s and G alpha q/11 were significantly reduced in glomerular membranes from rats with BUO when compared to SOC rats. No significant difference in total G alpha i, G alpha i2 and G alpha i3 and G beta content was observed between the two groups of rats. In vivo pretreatment of rats with simultaneous administration of the angiotensin converting enzyme inhibitor, enalaprilat, and the thromboxane synthase inhibitor, OKY-046, maintained the amount of G alpha s and G alpha q/11 in rats with BUO at the levels seen in SOC rats. The two drugs did not affect the amounts of G protein subunits in glomerular membranes of SOC rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479123 TI - Gianturco self-expanding stent in the treatment of stenosis in dialysis access grafts. AB - This study evaluated the effectiveness of the Gianturco endovascular stent in preserving graft patency following percutaneous transvenous angioplasty (PTVA) of stenotic lesions occurring at the graft-vein anastomosis in hemodialysis patients with polytetrafluoroethylene grafts. Fifty-eight patients having 50% or greater stenosis were randomly divided into a treatment group (N = 28) and a concurrent control group (N = 30) following PTVA. In the treatment group, a stent was placed following dilatation. Graft thrombosis, the need for surgical revision, or the need for a repeat PTVA were used as end point events. The period of time from the PTVA/stent procedure to the end point event was referred to as the duration of efficacy (DE). By life table analysis, the DE for the treatment group was 100% at 30 days, 91% at 60 days, 85% at 90 days, 72% at 180 days, and 17% at 360 days. Comparison of the characteristics and results obtained in the treatment group and that of the concurrent control group revealed no significant difference in any parameter prior to treatment, in the response to PTVA, or in the DE of the procedure performed. It was concluded that the stent offered no advantage in the treatment of the graft-vein anastomosis stenotic lesion affecting PTFE dialysis access grafts. PMID- 8479124 TI - Soluble CD23 as an effector of immune dysregulation in chronic uremia and dialysis. AB - Patients with chronic renal failure often present an immunodeficiency state paradoxically exacerbated by hemodialysis and associated with signs of T cell activation. The presence of circulating monokines suggests that monocytes are also activated. Whether or not this includes B cells is controversial, despite frequently abnormal antibody responses. We thus investigated whether the soluble low-affinity receptor for IgE (Fc epsilon RII/CD23), recently identified as a marker of B cell and monocyte activation and possibly involved in T cell activation, was modulated by chronic renal failure and hemodialysis. Relative to values in healthy individuals (N = 31), plasma concentrations of soluble CD23 were significantly elevated in non-dialyzed chronically uremic patients (N = 44), more elevated in patients on peritoneal dialysis (N = 24), and most elevated in those on regular hemodialysis (N = 132), stabilizing after about six months. Soluble CD23 levels were unmodified by the first dialysis session but rose markedly during regular dialysis with cellulose or polysulfone membranes, but not with polyacrilonitrile AN-69 membranes. Soluble CD23 levels correlated with levels of IgG, and those of tumor necrosis factor alpha and interleukin-6, suggesting that increased sCD23 levels reflect activation of B cells and monocytes, respectively. These findings reinforce the view of soluble CD23 as a multi-functional receptor/cytokine, and provide evidence that it might contribute to the immune dysregulation associated with chronic renal failure and exacerbated by hemodialysis. PMID- 8479125 TI - 31P NMR spectroscopy investigation of muscle metabolism in hemodialysis patients. AB - Calf muscle metabolism of six patients with end-stage chronic renal failure undergoing maintenance hemodialysis and of six control subjects was studied using 31P nuclear magnetic resonance spectroscopy at 4.7 Tesla. Spectra were obtained at rest, during exercise and recovery. At rest, the inorganic phosphate, ATP and phosphocreatine concentrations, and the intracellular pH were similar in both groups of subjects. In the patients, the maximum workload achieved at the end of exercise led to a 84% and 46% depletion of phosphocreatine and ATP, respectively; under this condition, the intracellular pH fell to 6.50 +/- 0.09. In control subjects, a maximum workload caused no change in ATP concentration at the end of exercise, but a phosphocreatine depletion and an intracellular pH fall similar to those observed in the patients. Although the rate of phosphocreatine depletion during exercise was not different in the two groups of subjects, the decrease in intracellular pH was more rapid in the patients than in control subjects. At the end of maximum exercise, the rates of recovery of both phosphocreatine and intracellular pH were significantly reduced in the muscle of hemodialysis patients when compared to normal subjects. These results suggest that, in the calf muscle of hemodialysis patients, energy production via oxidative metabolism is impaired and compensated for by an increase in anaerobic glycolysis. PMID- 8479126 TI - Serial measurements of GFR in infants using the continuous iothalamate infusion technique. Southwest Pediatric Nephrology Study Group (SPNSG). AB - We undertook a preliminary study to determine if a clinical trial was feasible that would compare the effect of a low protein vs a control formula on GFR and growth in infants with congenital renal insufficiency (CIo < 55 ml/min/1.73 m2). In this report from the Infant Diet Protein Study, we describe validation of a method using the plasma clearance of iothalamate (CIo) as an estimate of glomerular filtration rate (GFR) and results of the preliminary study relating to renal function. The plasma CIo method was validated as an accurate estimate of GFR by showing it to be the same as the plasma clearance of inulin (CIn). In the preliminary study infants who qualified for the study were randomly assigned to a low protein or control formula and were followed from 8 to 18 months of age. CIo was measured at 8, 14 and 18 months of age in 21 of the infants and at 8 and 18 months of age in all twenty four infants that entered the study. Average absolute GFR in the 24 infants increased in the 10 month period from 5.3 +/- 2.7 to 7.6 +/ 4.5 ml/min. The percent increase in GFR was no different in infants whose GFR at 8 months of age was severely reduced from those whose GFR was only moderately reduced. When adjusted for age and body size, GFR did not change. Change in mean CIo or serum creatinine (SCr) from 8 to 18 months of age between the infants in each diet groups was not different. We conclude that a clinical trial enrolling more infants and extending the study period is necessary to evaluate dietary protein effect. PMID- 8479127 TI - Aluminum kinetics using bicarbonate dialysate with the sorbent system. AB - In the REDY system a sorbent cartridge is used to regenerate the spent hemodialysate so that only six liters of dialysate are required for a treatment. The manufacturer claims that the cartridge can be used to remove aluminum from the dialysate and that it does not add aluminum to the dialysate. This claim for acetate dialysate is supported by the literature, but there are few data available relative to bicarbonate dialysate. The present study evaluates the use of bicarbonate dialysate and the REDY system in regard to aluminum kinetics both in vitro and in vivo. In vitro, the sorbent cartridge removed aluminum from dialysate prepared from water containing as much as 470 micrograms/liter of aluminum, giving a dialysate containing less than 10 micrograms/liter. The first 500 ml of effluent contained 13 micrograms/liter of aluminum but after filtration decreased to below 10 micrograms/liter. Thus, it is unnecessary, as recommended, to discard the first effluent since this unfilterable aluminum will not pass through a dialysis membrane. In vivo, in a crossover study comparing the REDY with single pass, there were no significant differences between the pre- and post plasma aluminum concentrations, and the dialysate aluminum remained below 4 micrograms/liter during the dialysis. In a second in vivo study the effect of dialysate from tap water on plasma aluminum using the predialysis purification procedure was evaluated. There was no differences between the pre- and post plasma aluminum concentration. The aluminum levels were comparable to those of the crossover study. The dialysate remained below 4 micrograms/liter during the dialysis. PMID- 8479128 TI - Adsorption of complement factor D by polyacrylonitrile dialysis membranes. AB - Factor D, an essential enzyme of the alternative pathway (AP) of complement, accumulates in end-stage renal failure (ESRF). Polyacrylonitrile (PAN) membrane activates complement poorly and has been shown to adsorb C3a, the main anaphylatoxin released during complement activation. In the present work we investigated whether factor D might be adsorbed on PAN. In vitro there was a loss of hemolytic factor D when normal human serum (NHS) was incubated with PAN dialysis fibers, whereas no loss was observed with cuprophan (Cu) fibers. There was a dose and time dependent binding of purified radiolabeled factor D to PAN but not to Cu. The hemolytic function of factor D released from PAN by 2 M NaCl was normal. By contrast, factor D was inactive while adsorbed to PAN fibers. When 50 ml of NHS or 100 ml of whole blood were passed through a new hollow fiber PAN dialyzer 95% of factor D was adsorbed. The eluate from a PAN filter which had been used for dialysis in a patient with ESRF contained 38.4 mg of hemolytic factor D, representing 34% of the proteins eluted. By immunoblotting, antigenic factor D from the PAN eluate was identical to purified human factor D. In six patients there was a 81.4% decrease in hemolytic factor D in blood after dialysis with PAN, contrasting with a 9.6% decrease in those dialyzed with cellulose acetate. No factor D was found in the dialysis fluid of PAN dialyzers, indicating that PAN removed factor D mainly by adsorption. In conclusion, PAN has a significant capacity to adsorb factor D, a reaction that might contribute to the diminished capacity of PAN membrane to activate the AP of complement. Whether the efficient removal of large amounts of factor D might be beneficial in uremic patients remains to be defined. PMID- 8479129 TI - A multivitamin infusion prevents lipid peroxidation and improves transplantation performance. AB - The objective of this study was to test the hypothesis that ischemia reperfusion damage in kidney transplantation is associated with lipid peroxidation and that inhibition of lipid peroxidation by antioxidants improves the function of the transplanted kidney. Lipid peroxidation was assessed by measuring the plasma malonaldehyde content (as thiobarbituric acid reaction product) with high performance liquid chromatography. Kidney function was assessed by plasma creatinine and creatinine clearance. Thirty patients of an ongoing series were randomly selected into two groups, with 14 controls and 16 patients in the antioxidant therapy group. Therapy consisted of two ampoules of Omnibionta (which contains vitamins C, E, A and B complex) diluted in 500 ml physiological sodium chloride, which was infused intravenously prior to reperfusion onset. No significant differences existed for the age of the patients in the control (43.00 +/- 9.86 years) and the therapy group (41.56 +/- 14.14 years) nor in the kidney preservation time, which was 24.12 +/- 8.73 and 18.43 +/- 9.97 hours in the control and therapy group, respectively. The controls showed a transient increase of plasma lipid peroxides as measured by malonaldehyde with a peak one hour after onset of reperfusion. Compared to the baseline value of 0.74 +/- 0.26 (mean +/- SD) the one hour malonaldehyde value increased to 1.46 +/- 0.22 nmol/ml (P < 0.001). In the therapy group the plasma malonaldehyde level did not increase, but slightly decreased by about 20% compared to the baseline value. The difference of plasma malonaldehyde between the two groups one hour after reperfusion onset was highly significant (P > 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479130 TI - Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases. AB - This study offers morphological evidence of the involvement of lipid abnormalities in human glomerular injury. Renal biopsy tissues from patients with several types of glomerular diseases were immunocytochemically examined using antibodies to apolipoproteins (apo) A-I, B-100, and E, and antibodies to low density lipoprotein (LDL) receptors and scavenger receptors. Immunofluorescent staining showed the predominant deposition of apo B and apo E in the mesangial area in mesangial proliferative types of glomerulonephritis; the distribution and staining intensity of these apolipoproteins correlated with the grade of mesangial proliferation and proteinuria, but were independent of plasma lipid levels. Immunoelectron microscopy revealed that apo B and apo E were distributed in droplets within glomerular epithelial and mesangial cells or in a granular pattern in the expanded mesangial matrix. Apo A-I was mainly localized in the visceral epithelial cells of normal human kidneys. Staining for apo A-I was increased in the glomerular epithelial cells of nephritic kidneys, compared to the pattern in normal human kidneys, and was decreased in the sclerosed areas of glomeruli. An immunogold technique revealed the expression of LDL receptors on the surface membranes of glomerular mesangial and epithelial cells. Dual immunofluorescent staining showed that apo B and LDL receptors were occasionally co-localized in nephritic glomeruli. Scavenger receptor was detected on the plasma membranes of mesangial and visceral epithelial cells. The glomerular expression of scavenger receptor was increased in glomeruli with marked mesangial proliferation. In addition, the expression of this receptor was intense in monocytes/macrophages occasionally infiltrating the glomeruli. Our present findings indicate that in human nephritic kidneys, glomerular epithelial and mesangial cells express both LDL receptors and scavenger receptors. The accumulation of apolipoproteins, whether receptor-mediated or mediated by other mechanisms, can occur independently of plasma lipid levels, and may be associated with mesangial expansion and proteinuria. PMID- 8479131 TI - A crossover comparison of progression of chronic renal failure: ketoacids versus amino acids. AB - Rates of progression of chronic renal failure were compared in patients receiving alternately an amino acid supplement (AA) and a ketoacid supplement (KA) to a very low protein (0.3 g/kg), low phosphorus (7 to 9 mg/kg) diet. The first supplement was randomly chosen. Bias due to carryover effects was minimized by delaying the regression analysis until one month after starting or changing supplements. In order to minimize possible bias caused by initiating the two supplements at differing levels of severity, a multiple crossover design was used (ABA, BAB, ABAB, or BABA) with at least four GFR's in each treatment period (except for three GFR's in one instance). Sixteen patients completed the protocol; five dropped out. Average starting GFR's were nearly identical for the two supplements (15.4 and 15.9 ml/min). For each patient, mean progression on KA was compared with mean progression on AA. Thirteen out of 16 patients progressed more slowly on KA than AA. On the average, progression on KA was significantly slower (95% confidence limits = -0.36 to 0.09 ml/min/month) than on AA (-0.91 to 0.41 ml/min/month; P = 0.024). There was no significant difference in estimated protein intake, phosphate excretion, or mean arterial pressure between KA and AA periods. Serum triglyceride concentration was significantly lower on KA (P = 0.0026). 17-hydroxycorticosteroid excretion was also lower (P = 0.031). We conclude that KA slow progression, relative to AA, independently of protein or phosphorus intake, in patients on this regimen. PMID- 8479132 TI - [Secondary retinal detachment]. PMID- 8479133 TI - [Retinopathy of prematurity and retinal detachment]. AB - The authors examined 60 children (91 eyes), aged 5 months to 17 years, with retinal detachment in the ROP course; 19 eyes were selected for the surgery, 5 eyes with the active ROP phase and 14 myopic eyes with the vitreo-retinal changes resulting from ROP. The segmental or encircling scleral buckling was performed in 19 eyes, in 4 eyes the vitrectomy and the endo-tamponade was used. In 12 eyes (63%) the retinal attachment was achieved, in 2 eyes in the active phase (40%) and 10 eyes (71.3%) with regressed ROP. PMID- 8479134 TI - [Clinical course and treatment of angiomatosis of the retina]. AB - Basing on 11 cases of angiomatosis retinae, diagnosed and treated in the last 30 years in the Ophthalmological Clinic in Halle, the authors discussed the problems concerning this rare disease. Their observations confirmed the opinion that photocoagulation is the method of choice in the treatment of angiomatosis retinae and that it is successful in small, less than 2 disc diameter angiomas. The further possible therapeutical methods are cryocoagulation, radioactive-isotopes and vitrectomy. As the treatment should be repeated and the long-lasting follow up is necessary, the efficient cooperation with the patients is very important. PMID- 8479135 TI - [Treatment of secondary retinal detachment in von Hippel-Lindau disease]. AB - In the last 16 years, 8 patients (9 eyes) with secondary retinal detachment in von Hippel-Lindau disease were treated. The methods of treatment depended on the size and number of vascular tumours and on the extent and type of retinal detachment. The retina was successfully reattached in 4 eyes. In 4 eyes with the total retinal detachment, our treatment was uneffective. One patient is treated till now. The best results were observed when the tumours were small and single and the retinal detachment extended to less than 1 quadrant of the fundus of the eye. The successful therapy is conditioned by the complete destruction of the tumour. The treatment of the large retinal detachment, in spite of using different methods, is very often difficult and unsuccessful. PMID- 8479136 TI - [500 operations of retinal detachment. Early and long-term evaluation]. AB - The early and long-term postoperative results of 453 patients (510 eyes) with retinal detachment, treated with several buckling procedures, have been analysed. The follow-up, ranging from 2 to 9 years, revealed that the better anatomical and functional results were observed in the group of 325 eyes, in which the complete subretinal fluid drainage had been performed during the surgery, compared with 185 non-drained eyes. PMID- 8479137 TI - [Intraocular tamponade with SF6 gas in the treatment of selected cases of retinal detachment]. AB - The aim of this paper is to present the results of the endotamponade with SF6 gas in the treatment of 19 patients with retinal detachment. The cases selected for the surgery were characterised by the retinal tear situated in the upper part of the fundus of the eye or in the posterior pole with no symptoms of PVR phase C and D and vitreo-retinal traction. The indications for endotamponade, the causes of failures and the complications connected with this kind of surgery were discussed. PMID- 8479138 TI - [Blood-retinal barrier and visual field in retinitis pigmentosa]. AB - The aim of the research was to determine, with new-generation fluorometer (Fluorotron Master), the factor of fluorescein leakage into the vitreous and to reveal, with the static perimeter (Humphrey's), the quantitative parameter of the visual field in retinal pigmentary dystrophy. The factor of fluorescein leakage into the vitreous was almost ten times higher in retinal pigmentary dystrophy and it indicated the damage of blood-retina barrier. The correlation between the factor of fluorescein leakage into the vitreous and the degree of visual field defect has not been found. PMID- 8479139 TI - [Retinoschisis vs. retinal detachment--diagnosis and treatment]. AB - In the years 1985-1990, 987 patients with retinal detachment were treated in the Ophthalmological Clinic of Medical Academy in Poznan. In 25 patients, from the above group, the coexistence of retinoschisis was observed. The clinical picture of retinal detachment and retinoschisis was the basis for explaining the pathogenesis of two different phenomena: "retinoschisis versus retinal detachment" and "retinal detachment versus retinoschisis". The surgical treatment applied to 25 eyes resulted in 88% retinal attachment. PMID- 8479140 TI - [Clinical examinations on pathogenesis and treatment of serous macular detachment associated with congenital optic pit]. AB - The author reports two clinical tests performed in 6 patients for explaining the pathogenesis of serous macular detachment associated with congenital optic pit. The results of these tests indicate, that the detachment is caused by the fluid of vitreal origin. The treatment of this disease with the laser coagulation is also reported. PMID- 8479141 TI - [Serous macular detachment caused by congenital optic pit]. AB - The observations concerning the treatment of 5 patients suffering from the serous macular detachment caused by the optic pit are presented. In all 5 cases, the laser photocoagulation along the temporal margin of disc was applied. The retinal attachment was obtained in 2 eyes. PMID- 8479142 TI - [Use of transconjunctival cryoapplication in chronic pars planitis with involvement of peripheral retina and choroid]. AB - The transconjunctival cryoapplication was performed in 8 patients (13 eyes) with the recurrent pars planitis and the simultaneous involvement of peripheral retina and choroid. Before the surgery, the peripheral fundus of the eye was examined with the Goldmann three-mirror lens and afterwards, the cryoapplication of lesions was performed. The topical treatment, dexamethasone and indomethacin drops, followed the surgery only. In all cases the inflammation disappeared but the macular edema and vitreal exudation regressed slowly. The considerable improvement of visual acuity was achieved in 8 eyes (61%). So far, the results of the observations are satisfactory and they entitle the authors to carry on the application of the treatment mentioned above. PMID- 8479143 TI - [Simultaneous bilateral retinal detachment as a delayed consequence of retinopathy of prematurity]. AB - The case of prematurely born woman, aged 22, with bilateral retinal dialysis and detachment in high myopic eyes is presented. The minor head-trauma preceded the onset of the detachment. The segmental scleral buckling procedures were performed in both eyes. The attachment of the retina and some improvement of visual acuity were achieved. PMID- 8479144 TI - [History of the department of Ophthalmology in Krakow from 1851-1991]. PMID- 8479145 TI - Oxidized lipoproteins and leukocyte-endothelial interactions: growing evidence for multiple mechanisms. PMID- 8479146 TI - Neuroexcitation, excitotoxicity and human neurological disease. PMID- 8479147 TI - Capillary endothelium. Target site of renal radiation injury. AB - BACKGROUND: Therapeutic abdominal irradiation may be accompanied by late occurring progressive renal disease associated with glomerular mesangial sclerosis and tubular degeneration. Pathogenesis of this lesion is disputed. EXPERIMENTAL DESIGN: Kidneys of mature pigs were irradiated with a single dose of 9.8 Gy 60Co gamma-rays; serial individual kidney glomerular filtration rate and renal biopsies were obtained at 3-4-week intervals with death 24 weeks after irradiation. RESULTS: Irradiated pigs displayed a progressive reduction in glomerular filtration rate with minimal values observed 12 weeks postirradiation. Morphologic changes in irradiated glomeruli were characterized by leukocytic attachment to capillary endothelial cells 3-6 weeks after irradiation followed by activation and swelling of endothelial cells and occasional microthrombi formation. Similar changes were noted focally in peritubular capillaries with accompanying tubular degeneration and atrophy. In glomeruli these endothelial cell changes were followed by increased capillary permeability and fluid, erythrocyte, platelet, and leukocytic exudation into the subendothelial/mesangial space resulting in compression of glomerular capillary lumina. By 12 weeks postirradiation mesangial cells showed evidence of activation and proliferation accompanied by progressive mesangial expansion and sclerosis with continued reduction of glomerular filtration rate. CONCLUSIONS: It is concluded that endothelial cell injury represents the primary site of radiation damage in the kidney and that the progressive glomerular mesangial sclerosis and reduced renal function of radiation nephropathy may be associated with exposure of capillary elements to various vasoactive and growth promoting factors that stimulate mesangial contraction and proliferation resulting in reduced glomerular filtration area and glomerular filtration rate. PMID- 8479148 TI - Increase production of fibronectin by glomerular cultures from rats with nephrotoxic nephritis. Macrophages induce fibronectin production in cultured mesangial cells. AB - BACKGROUND: The participation of monocytes-macrophages and their products in the pathogenesis of several types of glomerulonephritis has become increasingly evident. One of the most important aspects is the potential stimulation of monocyte-macrophages of the extracellular matrix. Therefore, production of fibronectin (FN) by glomeruli of rats with nephrotoxic nephritis was studied. In addition, the effect of macrophage-conditioned medium and interleukin-1 on FN production by cultured mesangial cell (MC) was tested. EXPERIMENTAL DESIGN: Nephrotoxic nephritis was induced in rats by injection of nephrotoxic serum and glomeruli obtained at different periods of time from nephritic and normal animals were cultured. FN in glomerular supernatants was determined by enzyme-linked immunosorbent assay and newly synthesized FN by incorporation of [35S] methionine. Macrophage-conditioned medium was obtained from cultures of peritoneal resident macrophages and elicited macrophages by different stimuli. MC were cultured with or without macrophage supernatant or interleukin-1 and FN content from MC supernatants was determined by enzyme-linked immunosorbent assay. RESULTS: These data show increase amounts of FN in nephritic cultures when compared with saline controls (time of nephritis; day 4: 3.9-, day 8: 4.35-, and day 18: 2.68-fold increase in FN) and experiments of newly synthesized FN by incorporation of [35S]-methionine had similar results. Macrophage-conditioned medium had FN stimulatory effect on cultured MC but interleukin-1 did not. CONCLUSIONS: These data suggest: (a) that there is an increased newly synthesized FN production in glomeruli from rats with nephrotoxic nephritis, (b) that macrophage produce a FN-stimulatory factor(s) for MC, and (c) that this stimulatory factor probably is not interleukin-1. PMID- 8479149 TI - Decreased synthesis and delayed processing of sulfated glycoproteins by cells from human polycystic kidneys. AB - BACKGROUND: In polycystic kidney disease, there is progressive distention of tubules and remodeling of an altered extracellular matrix. Recent findings indicate a defect(s) in the synthesis, post-translational modification, cellular transport, and extracellular matrix incorporation of proteoglycans in PKD that may have a fundamental role in its pathogenesis. EXPERIMENTAL DESIGN: Pulse-chase techniques and quantitative autoradiography were used to investigate in vitro the de novo synthesis and the kinetics of intracellular transport and extracellular matrix assembly of sulfated glycoproteins by epithelial cells from normal human kidneys (NK) and from cysts of autosomal dominant polycystic kidneys (ADPKD). NK and ADPKD cell monolayers were pulsed with [35S]sulfate for 150 min and chased for four intervals between 15 and 120 min. RESULTS: In ADPKD versus NK cells there was a significant reduction in the de novo synthesis of sulfated glycoproteins and, during the chase, a marked prolongation of the disappearance time for cellular sulfated glycoproteins. Transport kinetics revealed a substantial delay in processing and release of these macromolecules by the Golgi apparatus in ADPKD cells. During the chase, kinetics for the cellular transport of sulfated glycoproteins by secretory vesicles and their assembly into extracellular matrix were comparable in ADPKD and NK cells. However, the percentage of total sulfated glycoproteins incorporated into the matrix of ADPKD versus NK cell monolayers was notably diminished. CONCLUSIONS: The findings indicate that in ADPKD versus NK cell monolayers, synthesis of sulfated glycoproteins is impaired, processing of sulfated glycoproteins by the Golgi apparatus is prolonged, and assembly of these macromolecules into the extracellular matrix is reduced. These alterations may have a fundamental role in the pathogenesis of autosomal dominant polycystic kidney disease. PMID- 8479150 TI - Differences in expression of lupus nephritis in New Zealand mixed H-2z homozygous inbred strains of mice derived from New Zealand black and New Zealand white mice. Origins and initial characterization. AB - BACKGROUND: F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice develop autoimmune glomerulonephritis resembling human lupus nephritis. Susceptibility to this complex autoimmune syndrome in humans and mice has been linked to genes mapping in or near the major histocompatibility complex that govern immune responses and levels of certain complement components. Previous studies showed that both parental strains contribute major histocompatibility complex-linked genes that are important for disease of the F1 hybrid. EXPERIMENTAL DESIGN: New inbred strains of New Zealand Mixed (NZM) mice were derived by selective inbreeding of progeny of a cross between NZB and NZW mice. Twelve of the 27 new NZM strains were selected for analysis. Mice were observed for up to 10 months of age to document the occurrence of nephritis and strain specific differences in disease expression. H-2, Hc, and coat color loci were determined for each strain to establish homozygosity of NZB and NZW polymorphic markers. Strains were screened for the presence of anti-dsDNA autoantibodies. RESULTS: In some NZM strains early onset of lupus nephritis in females resembled the (NZB x NZW)F1 model, whereas in other strains early disease also occurred in males. Age at death and severity of nephritis vary among the lines; a few strains remain relatively free of glomerular lesions. Histocompatibility (H-2) typing showed that all strains are homozygous for the NZW haplotype (Ku, Au, Sz, Dz). Coat color analysis for four loci on chromosomes 2, 4, and 7 was consistent with specific reassortments and recombinations to explain the grey, tan, and white mice with red/pink eyes and the presence or absence of the fifth component of serum complement (C5) (Hc, chromosome 2). Anti-dsDNA autoantibodies were found in all but one of the NZM strains reported here. CONCLUSIONS: The NZM strains of mice are a unique set of inbred strains that have inherited various genomic segments of the two parental strains that lead to phenotypic differences in disease expression. These results indicate that the previously proposed strict requirement for H-2 heterozygosity for the development of nephritis in the (NZB x NZW)F1 hybrid mice may not be valid. It is assumed that both the Lpn-1 locus of NZB and the Lpn-2 locus of NZW and a sufficient number of other disease associated genes of both ancestral strains have been recombined in these new strains to produce the various patterns of renal disease. PMID- 8479151 TI - Ammonium chloride alters renal tubular cell growth and protein turnover. AB - BACKGROUND: Since renal hypertrophy occurs in conditions associated with increased renal ammonia genesis it has been suggested that ammonia may stimulate renal growth. Indeed, quiescent cultured tubular epithelial cells exposed to NH4Cl undergo hypertrophy. However, ammonia inhibits liver regeneration in vivo and proliferation of cultured fibroblasts. This study was designed to evaluate the effect of ammonia (NH3/NH4+) as a regulator of kidney cell hypertrophy and also kidney cell proliferation. EXPERIMENTAL DESIGN: Cultured opossum kidney cells and primary rabbit proximal tubular epithelial cells were grown with or without (controls) NH4Cl present. RESULTS: After 3 days exposure to 5-20 mM NH4Cl, there was a dose-dependent depression of cell replication that ranged between 8 and 63% compared with controls (p < 0.017). In contrast, cell volume and protein content were significantly greater in the NH4Cl-treated cells. At 20 mM NH4Cl the protein content of treated cells exceeded that of controls by as much of 75%. This difference in protein content could, in part, be related to the disparity in cell density. However, experiments performed with cells at similar density revealed that NH4Cl also has a direct effect on cell protein content that increased by 25%; this appeared to be a consequence of depressed protein breakdown and was not due to altered protein synthesis. Experiments with rabbit kidney cells revealed that inhibition of replication was associated with a decrease in DNA [3H]thymidine incorporation. Cell cycle analysis revealed a fall in the proportion of cells in the S + G2 + M phase compared with controls (22 versus 30%, respectively; p < 0.01). NH4Cl also inhibited the burst of replication that followed chemically induced hypoxic injury of quiescent opossum kidney cells. CONCLUSIONS: We conclude that in addition to inducing hypertrophy, NH4Cl can inhibit tubular cell proliferation. Thus, while heightened ammoniagenesis in vivo may favor hypertrophy, this in vitro study raises the question whether an elevated intrarenal ammonia content might be harmful when cell replication is required. Acute tubular necrosis is a condition in which elevated ammonia levels and a requirement for cell replication coexist and could serve as an important model to study this question. PMID- 8479152 TI - Anomalous structure of urinary chondroitin sulfate from cancer patients. A potential new marker for diagnosis of neoplasias. AB - BACKGROUND: Chondroitin sulfate is significantly increased in tumors (10 to 100 times) when compared to the amounts present in normal adjacent tissues. To investigate if the changes in concentration of chondroitin sulfate could be reflected in the urine of cancer patients we have analyzed the chondroitin sulfate excreted by 44 patients with different types of tumors, 50 normal individuals and 15 patients with unrelated diseases. EXPERIMENTAL DESIGN: The identification and structural analyses of the sulfated glycosaminoglycans were made by electrophoresis and degradation with specific enzymes (chondroitinases AC and ABC), identification/quantitation of their disaccharide products by chromatography (paper and HPLC) and chemical determinations. RESULTS: The disaccharide products formed from chondroitin sulfate of the 44 cancer patients by action of chondroitinase ABC show a substantial relative increase of non sulfated disaccharide (32.1% +/- 15.2) with a relative decrease of 6-sulfated disaccharide (28.9% +/- 11.5) and 4-sulfated disaccharide (39.0% +/- 13.5) when compared to the chondroitin sulfate of normal subjects (9.1% +/- 2.2, 40.6% +/- 4.5 and 50.2% +/- 4.5, respectively) or from patients with unrelated diseases. There is a direct correlation between the non sulfated disaccharide content and the stage of malignancy of the cancer patients. A significant change of the ratio of chondroitin sulfate and heparan sulfate and a decrease in the electrophoretic migration of chondroitin sulfate were also observed in cancer patients. CONCLUSIONS: All the cancer patients analyzed so far have shown the structural anomaly of the urinary chondroitin sulfate and this may be useful in the diagnosis and follow up of cancer therapy. PMID- 8479153 TI - Spontaneous evolution of cytoplasmic lectin binding and nuclear size and deoxyribonucleic acid content in human colorectal cancers grafted onto nude mice. AB - BACKGROUND: The development of certain biologic characteristics in human colorectal tumor xenografted onto nude mice are described with respect to their precocious passages, i.e., passaging below 10 onto athymic mice. EXPERIMENTAL DESIGN: The biologic characteristic monitoring involved the determination of modifications occurring in cytoplasmic lectin binding and spontaneous development in nuclear size and DNA content. The lectin immunohistochemistry included the characterization of staining modifications in the glandular parts of the colorectal xenografts of wheat germ, Dolichos biflorus, peanut, Solanum tuberosum and Ulex europaeus I agglutinins. The nuclear modifications were monitored by means of the digital cell image analyses of Feulge-stained nuclei. RESULTS: The results show that although the xenografted human colorectal lines may be relatively stable according to their macroscopic growth over serial passaging, certain of their microscopic characteristics develop markedly. Three lectins, i.e., wheat germ agglutinin, Solanum tuberosum, and Ulex europaeus I, showed a glandular binding which remained relatively stable over serial passaging, whereas the peanut binding exhibited some variations and the DBA binding progressively disappeared. These cytoplasmic modifications occurring over time were less pronounced than those that occurred with respect to nuclear measurements, i.e., size and DNA content. CONCLUSIONS: Nuclear DNA content heterogeneity as revealed by DNA histogram typing rather than by DNA index assessments increased markedly in the colorectal xenografts over their serial passaging on nude mice. PMID- 8479154 TI - Expression of HSP 70, immediate-early response and heme oxygenase genes in ischemic-reperfused rat liver. AB - BACKGROUND: Reperfusion of the liver after non-necrogenic ischemia induces the expression of the HSP gene and the synthesis of the hsp 70 protein, the best known among stress (heat-shock) proteins. EXPERIMENTAL DESIGN: We have studied the time course of the induction and the effects of cycloheximide treatment on the expression of c-fos, c-jun and the heat-shock gene HSP 70 in ischemic reperfused livers; extracts of these livers have also been examined for the binding to a synthetic oligonucleotide containing the heat-shock consensus sequence (HSE) in order to reveal the possible presence of an active heat-shock factor (HSF) in ischemic-reperfused tissue. RESULTS: Expression of HSP 70 gene appears only after a certain threshold of cell damage, is preceded by induction of c-fos and c-jun but does not depend on ongoing protein synthesis. The binding of HSF to HSE seems to start during the late period of ischemia, although the subsequent reperfusion increases the effect. The level of heme-oxygenase mRNA, an indicator of oxidative stress, increases in the liver after reperfusion but the oxidative stress caused by CoCl2 treatment does not induce the expression of HSP 70 gene under the conditions of the present experiments. CONCLUSIONS: We suggest that, similar to heat-shock, protein malfolding occurring during ischemia may trigger the HSP 70 gene induction, which is then amplified by the subsequent reperfusion stress. A model of chemically induced oxidative stress seems to be unable to induce the HSP 70 gene expression with the same characteristics of heat shock or ischemia-reperfusion. PMID- 8479155 TI - Protein kinase C activity and messenger RNA modulation by estrogen in normal and neoplastic rat pituitary tissue. AB - BACKGROUND: Estrogens stimulate pituitary cell growth by prolactin cell hyperplasia in normal rat pituitaries while inhibiting growth of transplantable rat pituitary tumors in vivo and in vitro. The mechanisms by which estrogens stimulate proliferation of normal and hyperplastic pituitary tissues while inhibiting growth of established transplantable tumors is unknown. Protein kinase C (PKC) is involved in proliferation and differentiation of many cells including those of the anterior pituitary gland. PKC has a major role in regulating pituitary hormone synthesis and secretion. Analysis of PKC activity in normal, hyperplastic and transplantable pituitary tumors may provide insight into the mechanism of estrogen action on tumor growth and differentiation in pituitary tissues. EXPERIMENTAL DESIGN: Normal female rats and female rats with transplantable pituitary tumors were treated with estradiol 17 beta (E2) in vivo and subsequently analyzed for PKC activity. Rats with GH3 pituitary tumors were treated with E2 in vivo and a GH3 pituitary cell line maintained in vitro were also analyzed for PKC activity after estrogen treatment. The calcium-dependent and calcium-independent PKC isozymes were analyzed by in situ and Northern hybridization in normal and neoplastic pituitary tissue using specific oligonucleotide probes to characterize the subtypes of PKCs present in pituitary tissues. The calcium-dependent PKCs were also analyzed by immunohistochemistry using specific antibodies to PKC alpha, beta and gamma. RESULTS: Estrogen treatment increased total PKC activity significantly in normal pituitaries, but did not change total PKC activity in transplantable MtT/F4 and MtT/W15 tumors or in GH3 cells in vivo or in vitro. The mRNAs for PKC alpha and beta were detected in normal and neoplastic pituitary tissues and were increased after estrogen treatment in normal pituitary and MtT/F4 tumors, but not in MtT/W15 tumors. The calcium-independent PKC delta, epsilon and zeta were also detected in normal pituitary and in transplantable pituitary tumors and in GH3 cells by Northern hydridization and the levels of these PKCs were also regulated by estrogens. CONCLUSIONS: Estrogen modulates PKC levels in pituitary cells with an increase in total PKC activity in hyperplastic pituitaries but not in transplantable pituitary tumors. Estrogen also regulates the mRNA levels of the calcium dependent and calcium-independent PKC isozymes. PMID- 8479156 TI - Light- and electron microscopical studies of interstitial cells of Cajal and muscle cells at the submucosal border of human colon. AB - BACKGROUND: It has been suggested that interstitial cells of Cajal (ICC) at the submucosal border of the colonic circular muscle are pacemaker cells. We studied smooth muscle cells and ICC at the submucosal surface of the circular muscle layer of the normal human colon. EXPERIMENTAL DESIGN: Resected, unaffected specimens from human colon were studied by light microscopy and transmission electron microscopy. RESULTS: Throughout the colon, the inner fourth of each circular-muscle lamella was covered with a layer of 2 to 15 muscle cells (ICMC) with a smaller diameter, more perinuclear organelles, and a greater glycogen content than the outer circular muscle cells. ICMC were interconnected by adherens junctions and close appositions. Small bundles of ICMC were present in the submucosa. ICC were identified in all regions of the colon (ascendens, transversum, and sigmoideum) at the submucosal border, in deeper parts of the submucosa in close contact with smooth muscle bundles as well as in the circular muscle and main septa. ICC had a continuous basal lamina, caveolae, dense bands, thin and intermediate filaments, dense bodies and a well-developed smooth endoplasmic reticulum. Mitochondria and granular endoplasmic reticulum were very abundant. Lipid droplets and glycogen granules were frequent. Thick (myosin) filaments were absent. Close contacts to nerves and gap junctions to other ICC or smooth muscle cells were exceptional. Fibroblast-like cells in the submucosa were rich in granular endoplasmic reticulum and intermediate filaments. They had few dense bands and caveolae. Mitochondria, smooth cisternae and glycogen granules were sparse, cytoplasmic dense bodies and a continuous basal lamina were lacking. Fibroblast-like cells were associated closely with collagen bundles and they had no close contacts with nerves, ICC or muscle cells. CONCLUSIONS: Throughout the normal human colon, submucosal ICC and ICMC are identified and distinguished from other cell types present. Their organization and cytology differ from that of other animal species. The ultrastructure of ICC and ICMC is compatible with important regulatory functions on the circular muscle in the entire human colon. PMID- 8479157 TI - Control of health care costs. PMID- 8479158 TI - Co-occurrence of substance use and loneliness as a risk factor for adolescent hopelessness. AB - This research among a sample of 1,915 Mississippi adolescents investigated whether lonely adolescents who use illicit substances were at increased risk of hopelessness. Relative risk of scoring within the severe hopelessness range was 6.9 for non-substance users who were lonely and 4.2 for substance users who were not lonely. Yet, relative risk for severe hopelessness in substance-using lonely adolescents was 25.2. Lonely, substance-using adolescents were 25 times more likely to be severely hopeless than the reference group composed of non-substance using, not-lonely adolescents. Lonely adolescents who get drunk also were 15.9 times more likely to be severely hopeless than the reference group. Because hopelessness often is an indicator of suicidal behavior, these results may have important implications for school health adolescent suicide prevention efforts. PMID- 8479159 TI - Applying community organization to developing health promotion programs in the school community. PMID- 8479160 TI - The school nurse's role in attention deficit hyperactivity disorder. PMID- 8479161 TI - Selected behaviors that increase risk for HIV infection, other sexually transmitted diseases, and unintended pregnancy among high school students--United States, 1991. PMID- 8479162 TI - Teacher offers a child's perspective of weapon use. PMID- 8479163 TI - Peer coaching: building collegial support for using innovative health programs. AB - To ensure students achieve intended benefits from effective health programs, it is necessary to maximize program implementation and maintenance. Peer coaching provides a post-inservice staff development approach for health educators to strengthen teacher use of new health programs during implementation trials. While peer coaching positively influences teacher behavior and student outcomes, previous coaching programs have been limited in scope, have not been theoretically derived or adequately evaluated, and have not been systematically applied to health programs. This paper addresses teacher needs during trials, reviews peer coaching program features, and proposes a model to guide future planning, evaluation, and research. In this model, critical components of the coaching program include classroom assessments, coaching team cluster meetings, and administrative support. Strategies based on Social Learning Theory and Diffusion Theory are incorporated into the peer coaching program to influence teacher perceptions of their work roles, capability to implement a program, and commitment to the new instructional program. Interrelations among components are discussed and directions for future research and practice are suggested. PMID- 8479164 TI - Death themes in literature for children ages 3-8. AB - Children's literature provides an appropriate tool for addressing concepts of death education. This study examined how death is presented in literature for children ages three-eight. A review of literature and Holsti's formula for intercoder reliability were used to develop a data collection instrument. Children's books with death themes were identified, and a content analysis recording frequencies for 39 items was performed on 65 books available for the study. A profile of the typical children's book with death themes was developed. The profile is discussed in terms of positive and negative presentations of death and being developmentally appropriate for young children. Based on results from the study, death themes are presented in a positive, realistic way that promote healthy development. Because of its positive presentations, children's literature is recommended as a teaching tool for death education. PMID- 8479165 TI - Correlates of condom use and number of sexual partners among high school adolescents. AB - Factors associated with condom use and number of sexual partners were examined in a statewide sample of public high school students in grades 9-12 (N = 3,893). Data were collected in spring 1990 using the 70-item, self-report Youth Risk Behavior Survey, developed and piloted by the Centers for Disease Control. Composite scores were constructed to measure aggression, physical recklessness, alcohol use, illegal drug use, cigarette use, lack of exercise, and academic self image. Since simple polychotomous logistic regression models revealed a significant race by gender interaction, multivariate models were run separately for each race-gender group. Odds ratios and 95% confidence intervals were calculated from polychotomous logistic regression of lifetime sexual activity and condom use with their potential correlates. Risky sexual behavior appears to be correlated with a complex of other behaviors that place students at risk. A pattern of declining condom use with increasing number of partners was evident, especially for White students. PMID- 8479166 TI - Predicting cigarette smoking among adolescents using cross-sectional and longitudinal approaches. AB - The ability to identify groups of children at risk of initiating a smoking habit may prove useful in developing effective smoking prevention programs. This report includes data collected over a three-year period, and attempts to predict adolescents' smoking behavior using both cross-sectional and longitudinal analyses. In addition, predictor variables reflecting both interpersonal and intrapersonal domains were included. Results indicated the highest rates of accurate classification into smoking categories were achieved with cross sectional analyses. In addition, interpersonal variables emerged as most important in all analyses. Implications for smoking prevention programming are discussed. PMID- 8479167 TI - Scintigraphic evaluation of bacterial translocation during hemorrhagic shock. AB - We investigated the use of gamma scintigraphy to evaluate the temporal and spatial patterns of translocation of radiolabeled Escherichia coli from the porcine jejunum during and following hemorrhagic shock. Thirteen healthy mixed breed pigs (22-43 kg) were randomly allocated to two groups. Pigs were anesthetized with sodium pentobarital (30 mg/kg) and mechanically ventilated (100% O2). Each pig was instrumented for mean arterial pressure (MAP) and superior mesenteric artery (SMA) blood flow determination. A 25-cm loop of vascularly intact distal jejunum was isolated, and 10 mCi (10(11) cfu) of radiolabeled E. coli (99mTcO4-) was placed within the bowel segment. Consecutive 5-min scintigrams of the entire abdomen and thorax were collected for 6 hr. Pigs in the shock group (n = 7) were hemorrhaged such that MAP was maintained at 50-60 mm Hg for 5 hr. Pigs in the sham group (n = 6) were maintained without hemorrhage for 6 hr. The total radioactive counts in the translocation regions of the scintigram were plotted against time, and the slope of the regression lines was compared between groups. In the shock group, SMA blood flow decreased significantly (P < 0.05) during the hypotensive period but returned above baseline during reperfusion. The mean (+/- SD) slopes for translocation regression lines were 9.3 +/- 11.4 counts/min and 36.3 +/- 33.7 counts/min in the sham and shock groups, respectively (P < 0.05). Translocation was scintigraphically evident 50-100 min following induction of hemorrhage and did not require reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479168 TI - Phorbol dibutyrate and ionomycin improve murine effector cell cytotoxicity. AB - Simultaneous protein kinase C stimulation with phorbol 12,13-dibutyrate (PDBU) and calcium mobilization with ionomycin (Io) trigger cellular events leading to expression of proliferation-associated genes in human lymphocytes. The effect of a 16-hr exposure to PDBU and Io on the growth and cytotoxic activity of murine splenocytes and tumor-infiltrating lymphocytes (TIL) cocultured with interleukin 2 (IL-2) was studied. PDBU + Io increased the number of cytotoxic effector cells that could be generated in lymphokine-activated killer cells (LAK) cultures (40 fold) and to a lesser extent in TIL (10-fold). DNA synthesis of TIL increased significantly when exposed to PDBU + Io. Also, TIL stimulated with PDBU + Io demonstrated in vitro tumor-specific lytic activity significantly greater than that of control TIL (500 lytic units vs 50). The cell-surface phenotype of TIL treated with PDBU + Io was identical to that of control TIL (> 95% CD-3+, CD-4-, CD-8+). Results of adoptive immunotherapy using splenocytes stimulated by PDBU + Io and cultured in IL-2 were identical to those achieved when standard LAK cultures were used. However, treatment using TIL stimulated by PDBU + Io led to a significant reduction in the number of pulmonary nodules compared to standard TIL. In addition, PDBU + Io-stimulated TIL maintained significant in vivo activity without the need for systemic IL-2 administration. Pharmacologic manipulation of cytotoxic precursor cells is a useful strategy for improving the generation of murine cytotoxic effector cells. By using PDBU + Io, cytotoxic lymphocytes could be generated with improved in vitro and in vivo activity. PMID- 8479169 TI - Pancreaticogastrostomy: preferred reconstruction for Whipple resection. AB - Anastomotic leak is the main complication after Whipple procedures. We reviewed retrospectively our experience with pancreatic cancer patients treated with Whipple resection and reconstruction with a pancreaticogastrostomy (PG) or a pancreaticojejunostomy (PJ). Ten patients operated between 1966 and 1990 composed the PJ group. Eight patients operated recently made up the PG group. Data on age, length of stay (LOS), survival, and complications (early and late) were noted from patient's charts. Patients in the PJ group had an average age of 58.3 years, a mean LOS of 60.3 days (median, 48 days), and a mean survival of 14.5 months. PG group patients had a mean age of 64.5 years, an average LOS of 14.3 days (median, 14 days), and an average survival of 10+ months. None of these differences were significant. Major complications in the PJ group included 2 leaks, 2 cases of pancreatic insufficiency, and 2 deaths related to the anastomotic leaks. Eleven other major complications occurred. The PG group patients did not have any leaks. One developed pancreatic insufficiency. Complications in the PG group were much less serious than those in PJ group. The longest hospital stay in the PG group was 20 days (range, 2-20) and 144 days (range, 11-144) in the PJ group. We conclude that PG is superior to PJ because of the decreased incidence of anastomotic leaks and the less serious nature of the complications associated with PG. PMID- 8479170 TI - Increased circulating cholecystokinin in obstruction-induced acute pancreatitis. II. Pancreatic duct obstruction with and without bile duct obstruction. AB - Pancreatic exocrine stimulation by cholecystokinin (CCK) has been implicated in the pathogenesis of experimental acute pancreatitis. Bile exclusion from the gut stimulates duodenal CCK release and exacerbates obstruction-induced acute pancreatitis. Pancreatic and bile duct obstruction increases circulating CCK concentration. We hypothesized that acute pancreatitis induced by pancreatic and bile duct obstruction would be ameliorated when bile was returned to the duodenum. As many small pancreatic ducts drain into the bile duct in rats, preservation of bile flow required the use of a bile shunt. We studied acute pancreatitis and the time course of circulating CCK increase in three groups of rats after: (1) sham operation (dissection, no obstruction), (2) bile and pancreatic duct obstruction, and (3) bile and pancreatic duct obstruction with bile shunt. The rats were killed at 3-, 6-, and 18-hr intervals after operation. Their blood was collected for measurement of CCK, amylase, and bilirubin concentrations. The pancreata were excised, weighed, and processed for histological examination. The shunting of bile back to the duodenum ameliorated the acute pancreatitis along with a simultaneous limitation of the rise in CCK concentration. This suggests that bile duct obstruction, another form of bile exclusion, exacerbates pancreatic duct obstruction-induced acute pancreatitis. The elevation in CCK concentration showed an early peak indicating that the potential role of CCK in the pathogenesis of obstruction-induced acute pancreatitis is predominantly in the early phase of its development. PMID- 8479171 TI - Colonoscopy for intermittent rectal bleeding: impact on patient management. AB - Rectal bleeding is a frequent presenting symptom of a number of benign anorectal disorders. However, it may also be a warning sign of more significant gastrointestinal pathology. For this reason, full colonic evaluation has been recommended in patients with intermittent bright red rectal bleeding. The purpose of this study is to evaluate the utility of colonoscopy in this setting. Data were prospectively collected on 125 colonoscopies performed on the surgical service at the Cleveland Wade Park Veterans Administration Medical Center during a two year period. During this period 33 patients underwent colonoscopy for the evaluation of intermittent bright red rectal bleeding. Fourteen patients had abnormal rectal exams, including hemorrhoids in 9, mass lesions in 3, prolapse in 1, and fistula in ano in 1. Colonoscopy was normal in only 7 (21%) of the 33 patients examined. Findings in the remaining 26 included 31 polyps in 14 patients, cancer in 3, AVM in 1, diverticula in 9, hemorrhoids in 4, and other benign lesions in 5. Positive findings on rectal examination had no relationship to findings at endoscopy, with abnormal findings in 52% of patients with normal rectal exams and in 27% of patients with abnormal rectal exams (P = 0.187, NS). Findings at colonoscopy resulted in a change in management in 16 (48%) of patients examined. In patients with intermittent rectal bleeding, the entire colon should be evaluated regardless of findings on rectal examination, as a significant number of patients will have concomitant findings. Colonoscopy is an excellent method for colonic evaluation in this setting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479172 TI - Tumor necrosis factor mediates disseminated intravascular inflammation (DII) in the genesis of multiple organ edema. AB - Multiple system organ failure (MSOF), resulting from a diffuse overwhelming inflammatory response, is frequently the cause of death in patients suffering either severe injury or infection. Previous studies have demonstrated increased circulating levels of tumor necrosis factor with both severe injury and infection. In addition, the intravenous administration of tumor necrosis factor (TNF) has been shown to induce systemic responses similar to those seen in patients with MSOF. The data from in vitro studies suggest that TNF-mediated events at the level of the microcirculation may be primary in the genesis of multiple system organ edema and dysfunction. We hypothesized that the intravenous administration of TNF would acutely induce alterations in the microcirculation that were associated with the development of multiple organ edema and cardiorespiratory impairment. The cremaster microcirculation model was used to quantitate changes in microvascular indices. We directly observed increased numbers of firmly adherent leukocytes to the microvascular endothelium and quantitated decreased leukocyte rolling along the surface of the endothelium as leukocytes became firmly adherent following TNF injection. This TNF-mediated leukocyte-endothelial adherence was also associated with the development of microvascular protein leakage. TNF also acutely induced arteriolar vasodilation and increased microvascular blood flow. These changes in microvascular parameters were associated with the synchronous development of TNF-mediated multiple organ edema and cardiorespiratory impairment. These data support the hypothesis that TNF acutely mediates disseminated intravascular inflammation resulting in multiple organ edema and subsequent hemodynamic instability. PMID- 8479173 TI - Impaired response to alloantigens in murine biliary obstruction. AB - Male Lewis strain rats underwent bile duct ligation and division (BDL), selective hepatic duct ligation (SHL), simple ligation and recanalization (RCN), or sham celiotomy (SC). Unoperated rats served as normal controls (NC). At intervals of 1, 2, and 3 weeks postoperatively, the popliteal lymph node assay was used to study host versus graft (HVG) response. LBN-F1 splenocytes (5 x 10(6)) were injected into the hind foot pads, and the contralateral foot pad was injected with medium as a control. The popliteal lymph nodes were removed and weighed 7 days later. In the BDL group, HVG response was significantly impaired at 1 (BDL, 12.9 +/- 5.1 mg; SC, 21.6 +/- 2.6; NC, 22.4 +/- 9.4; P < 0.005, BDL vs SC or NC), 2 (BDL, 12.6 +/- 5.6; SC, 19.1 +/- 3.0; NC, 15.8 +/- 5.8; P < 0.001, BDL vs SC), and 3 weeks (BDL, 8.9 +/- 3.9; SC, 21.7 +/- 6.3; NC, 16.7 +/- 3.8; P < 0.001, BDL vs SC or NC). SHL did not cause hyperbilirubinemia or impair the HVG response at 2 weeks (SHL, 17.2 +/- 4.5; NC, 16.7 +/- 7.4). The serum bilirubin was normal 2 and 3 weeks after RCN, and the HVG response was normal in both groups; however, the HVG response was somewhat lower at 2 weeks (RCN, 12.1 +/- 2.1) than at 3 weeks (RCN, 18.2 +/- 4.4; P < 0.01, RCN 2 weeks vs RCN 3 weeks). BDL causes significant impairment in the murine response to alloantigens as measured by the popliteal lymph node assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479174 TI - Arterial hemorrhage complicating pancreatic pseudocysts: role of angiography. AB - Major arterial hemorrhage associated with pancreatic pseudocysts represents a formidable complication with high mortality rates. This study was undertaken to analyze presentation and outcome and to assess the role of angiography in diagnosis and management of this complication. A retrospective review of 180 patients referred for surgical management of pancreatic pseudocysts from 1964 to 1991 identified 13 patients (7.2%) with arterial hemorrhage. Eight patients presented with intracystic hemorrhage, 4 with upper gastrointestinal bleeding, and 1 with intra-abdominal bleeding. Six patients had gastroduodenal artery bleeding, 4 splenic, and 1 each left gastric, right colic, and left gastroepiploic. The site of bleeding was identified with selective visceral angiography in 9 patients; evidence of pseudocyst bleeding was seen in 5 of 7 patients who had contrast-enhanced computerized tomography (CT) scans. Angiographic embolization for control of hemorrhage was used in 6 patients and operative control in 7. Over the past decade, bleeding has been controlled with angiographic embolization in all patients except 1 with massive bleeding due to splenic artery erosion. Average blood loss was less in patients treated with angiographic embolization (6.8 vs 17.5 units, packed red cells, P < .05, Wilcoxon rank sum test). The sole mortality was a patient with cirrhosis treated in 1969. Clinical presentation of pseudocyst bleeding is variable; the underlying cause is usually related to chronic pancreatitis due to alcohol abuse. The dynamic contrast-enhanced CT scan is valuable in demonstrating evidence of pseudocyst bleeding. Accurate diagnosis with dynamic CT scan and angiography and control of bleeding with angiographic embolization has improved the outcome in patients with this complication. PMID- 8479175 TI - Comparison of techniques for harvesting enterocytes for transplantation. AB - Selective enterocyte transplantation is a potential alternative to small intestinal transplantation for treatment of the short bowel syndrome. Our aim was to compare chelation and enzymatic methods of isolating enterocytes with respect to initial cell yield and characteristics and in vitro growth. Enterocytes were harvested from adjacent ileal segments in 35 rabbits using chelation with EDTA and warm trypsinization. Determinations were made of initial viability by trypan blue exclusion, cell yield, and proportion of intact crypts. Cells (5 x 10(6)) were seeded in growth media into culture vessels. Cell attachment was estimated by measuring cells liberated by Dispase at 24 hr. In vitro growth was assessed at 14 and 28 days. Although total cell yield (15.0 +/- 9.9 vs 12.5 +/- 8.3 x 10(6) cells/cm) and intact crypts were similar, the trypsin technique resulted in cells with higher initial viability (86 +/- 7 vs 71 +/- 18%, P < 0.05). Cell attachment (7 +/- 8 vs 8 +/- 4%) and enterocyte disaccharidase activity were similar using both techniques. While the number of epithelial cell growth foci was not significantly different at 14 days, there was significantly greater surface coverage on both plain (44 +/- 20% vs 1 +/- 0%, P < 0.05) and Matrigel-coated (80 +/- 14 vs 16 +/- 25%, P < .05) vessels at 28 days with trypsin-isolated cells. Trypsinization resulted in a cell population which had a higher percentage of viable cells but a similar proportion of intact crypts and differentiated cells compared to those resulting from the chelation technique. Trypsin-liberated cells had greater capacity for in vitro growth particularly on Matrigel-coated surfaces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479176 TI - Limb-threatening ischemia complicated by perigenicular infection. AB - When graft infection or infection of the medial leg or popliteal fossa precludes a standard approach to revascularization of the ischemic leg, the literature suggests amputation may be the most prudent course because of excessive perioperative mortality and morbidity of attempts to reestablish axial flow. The purpose of this study is to define the outcome of revascularization when limb threatening ischemia is complicated by perigenicular infection. Of 1020 infrainguinal reconstructions performed since 1984, nine (0.9%) presented with limb-threatening ischemia and graft or wound infections involving the popliteal fossa (6) or medial thigh or calf wounds (3) which precluded standard revascularization in the five women and four men. Risk factors for infection included diabetes mellitus (5/9), wound hematoma at initial operation (2/9), and intravenous drug abuse (1/9); Staphylococcus aureus was the predominant organism in all infected wounds and two popliteal fossa infections. The other deep infections grew group D streptococci, Enterococcus, and Salmonella. Extra anatomic reconstruction was performed from the femoral (7) and iliac vessels (2) extending to the below-knee popliteal (2), the anterior tibial (4) and the peroneal (3) arteries using vein (5), and PTFE (4) in a lateral tunnel which avoiding the plane of the infection. Postoperative complications included MI (1), early graft thrombosis (2), and osteomyelitis of the femur (1); there were no deaths. With a mean follow-up of 19 months (3-57 months), primary graft patency was 66% and secondary patency was 78%, resulting in salvage of 66% of extremities at risk. These data demonstrate the safety and efficacy of extra-anatomic reconstruction for maintaining axial flow when limb-threatening ischemia is complicated by perigenicular infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479177 TI - The effect of protein binding on the adherence of staphylococci to prosthetic vascular grafts. AB - Staphylococcus epidermidis is the major bacterium causing prosthetic vascular graft infections and the ability of some S. epidermidis strains to produce slime is associated with pathogenicity. This study investigated the effect of protein binding of staphylococci as a possible mechanism affecting bacterial adherence to vascular graft materials. Slime- and non-slime-producing S. epidermidis strains and an encapsulated Staphylococcus aureus were incubated with Dacron or expanded polytetrafluoroethylene (PTFE). The slime-producing RP-62A strain had significantly greater adherence to all materials than the other bacteria tested and coincubation with serum did not affect its adherence. The adherence of all bacteria was greater to Dacron than to PTFE. Serum increased the adherence of S. aureus to PTFE (P < 0.05) but did not significantly alter the bacterial adherence to other materials. This suggests that protein binding does not affect the adherence of S. epidermidis to prosthetic vascular grafts. PMID- 8479178 TI - The regulation of mitochondrial fatty acid oxidation and hepatic gene expression by catecholamine. AB - We hypothesized that dopamine or dobutamine may alter hepatic mitochondrial fatty acid oxidation secondary to an effect on hepatic gene expression. We investigated the effect of dopamine or dobutamine on hepatic fat oxidation and gene transcription by studying the enzyme carnitine palmitoyltransferase (CPT), the rate-limiting step in hepatic mitochondrial long-chain fat oxidation. We incubated either H4IIE rat hepatoma cells or rat hepatocytes in primary cell culture with either dopamine (1, 0.1, 0.01 microgram/ml), dobutamine (1, 0.1, 0.01 microgram/ml), or vehicle control for 1, 2, 3, or 4 hr. We investigated the effect on (1) CPT mRNA (Northern or dot blotting) and the possible regulatory mechanism by incubating dopamine (0.1 microgram/ml) or dobutamine (0.1 microgram/ml) with propranolol or phentolamine, (2) CPT translation (CPT [35S]methionine incorporation), and (3) hepatic mitochondrial fatty acid oxidation ([1-14C]-palmitate oxidation to acid-soluble products). We conclude that (1) dopamine or dobutamine increases both hepatic CPT mRNA and CPT protein translation, (2) the effect on CPT mRNA is mediated by the beta-receptor, (3) the increase in hepatic mitochondrial fat oxidation induced by dopamine or dobutamine may be, in part, secondary to increased CPT transcription and translation, and (4) the significant difference in hepatic fat oxidation induced by dopamine as compared with that by dobutamine is secondary to factors other than transcriptional or translational mechanisms. We speculate that dopamine treatment in the critically ill may increase hepatic mitochondrial fatty acid oxidation and ketogenesis and that this increase in beta-oxidation may be, in part, secondary to increased CPT gene expression. PMID- 8479179 TI - POEMS syndrome in association with Sweet's syndrome--a new variant? PMID- 8479180 TI - An evaluation of residents' recognition of depressive symptoms in obstetrical patients. PMID- 8479181 TI - The impact of OBRA '90 on the pharmacist-patient-physician relationship. PMID- 8479182 TI - Scalping injuries: report of a historical case. PMID- 8479183 TI - Hepatomegaly and weight loss. PMID- 8479184 TI - Gross hematuria and easy bruising in a young man. PMID- 8479185 TI - High blood pressure: new efforts in primary prevention and disease management. PMID- 8479186 TI - Outpatient risk--inpatient injury. PMID- 8479187 TI - Reassuring patients about infection control. TMA Communications and Public Service Committee. PMID- 8479188 TI - Controlling costs after a workers' comp injury. PMID- 8479189 TI - OSHA stuff and nonsense. PMID- 8479190 TI - Breast cancer and the menstrual cycle. PMID- 8479191 TI - Significance of in vitro attachment of human colon cancers to extracellular matrix proteins in experimental and clinical liver metastases. AB - The attachment of 7 human colon cancer lines transplantable into nude mice, and primary tumors and liver metastases from 30 patients with colon cancer to 4 extracellular matrix proteins (EMPs)--Matrigel, laminin, fibronectin, and type IV collagen--was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H (MTT) assay. Cancer cells from the 4 established tumor lines which produced experimental liver metastases in vivo showed significantly greater attachment to each EMP than those from the other 3 tumor lines which did not. Although there were no significant differences between attachment to EMPs of cancer cells from 15 clinical primary tumors with liver metastases and those without, attachment to each EMP of cells derived from liver metastases was significantly greater than that of the cells from the corresponding primary tumors in 8 cases for which liver metastases and primary tumors were examined simultaneously. Attachment to EMPs, which could be determined simply and rapidly using the MTT assay, is thus considered a significant factor in experimental and clinical liver metastases of human colon cancers. PMID- 8479192 TI - Wound bleeding after head and neck surgery. AB - Using our head and neck service database, we reviewed 3,200 surgical procedures performed at our institution over a 7-year period. We identified 54 patients whose surgery was complicated postoperatively by wound bleeding. The procedure most often complicated by wound bleeding was parotidectomy, 1.7% (14 of 510 patients), followed by thyroidectomy, 1.6% (8 of 504 patients), neck dissection combined with other procedures, 1.3% (12 of 885 patients), and neck dissection alone, 1.1% (6 of 534 patients). Bleeding developed in flap donor sites in 2 of 227 patients and followed miscellaneous procedures in 12 others. Thirty-one patients were treated by reexploration in the operating room, 13 had limited exploration on the ward and 10 were observed with no intervention. There was no difference in wound healing between the three treatment groups. However, mean hospital stay was shortest for patients who had wound exploration in the operating room, 6.2 days, for exploration on the ward, 10.8 days, and 18.9 for those that were observed. Drains had no effect on wound healing or mean hospital stay. PMID- 8479193 TI - A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: a Radiation Therapy Oncology Group (RTOG) study. AB - The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2 year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress. PMID- 8479194 TI - The influence of surgical margins on advanced cancer treated with intraoperative radiation therapy (IORT) and surgical resection. AB - Intraoperative radiation therapy (IORT) has been used successfully in the treatment of malignancies, alone and as an adjunct to surgical resection. This study examined a single institution's experience with combined IORT and surgical resection in the treatment of advanced cancer. The records of 41 consecutive patients undergoing intraoperative radiation therapy (IORT) at the Fox Chase Cancer Center, from July 1987 through March 1990, were retrospectively reviewed. All patients had locally advanced disease, of whom 73% had failed previous multimodality therapy and 44% had undergone prior radiation therapy (XRT). The 2 year actuarial survival for the entire cohort was 72%. Disease-free survival was 47% at 1 year and 5% at 2 years. The only important prognostic factor predicting outcome was status of the surgical margin. Positive surgical margins decreased the 2-year actuarial survival from 100% to 59%, and increased the local failure rate from 21% to 52%. Margin status had no effect on the later development of metastatic disease. Higher IORT doses, field sizes > 7 cm, and multiple IORT fields were used for larger tumors and larger amounts of residual disease. These parameters alone did not correlate with improved local control. This analysis suggests the usefulness of aggressive surgical resection with IORT in extending survival for locally advanced or recurrent cancer. Negative margin status is the best predictor of a favorable outcome and should be used to select patients who may benefit from IORT. The use of radiation sensitizing agents should be explored in patients with positive margins, since in-field failure continues to be the major pattern of failure. IORT in conjunction with aggressive surgical resection should continue to be studied in prospective randomized clinical trials. PMID- 8479195 TI - Immunohistologic analysis of the extracellular matrix components of the fibrous stroma of human colon cancer. AB - In order to elucidate the gross composition of fibrous stroma and to better understand the obstructive nature of advanced human colonic cancers the extracellular matrix components of its stroma were analyzed immunohistologically, emphasizing the process of fibrosis and possible tissue constriction. Collagenous material, identified by Masson's trichrome stain, was distributed mainly in the invasive area, where type I and III collagens and chondroitin 4-sulfate stained intensely in the periacinar area, and further, fibronectin stained. Conversely, in the invasive area away from tumor acini type III collagen stained weakly and fibronectin not at all. Type V collagen and myofibroblasts stained in the periacinar area and did not stain in the invasive area away from tumor acini, the findings of myofibroblasts being prominent in cases with obstructive type carcinomas. In conclusion, the invasive area, especially the periacinar area, displayed signs of active ongoing fibrosis and tissue contraction, which may be responsible for the genesis of obstructing type colonic carcinomas. PMID- 8479196 TI - Breast Cancer Detection Demonstration Project data can determine whether the prognosis of breast cancer is affected by the time of surgery during the menstrual cycle. AB - The purpose of this study was to determine the feasibility of using Breast Cancer Detection Demonstration Project (BCDDP) data to ascertain whether the prognosis of breast cancer in premenopausal women is affected when surgery is performed relative to the different phases of the menstrual cycle. In the Louisville BCDDP only 40 cases were available for study, but even with this small number, the data indicate that survivorship was superior when the surgery was performed between days 7-20 of the menstrual cycle (P < 0.06). One thousand eighty-seven premenopausal women underwent surgery for breast cancer during the first 5 years of the national BCDDP, beginning in 1972. This large number of cases, plus the long period of follow-up should provide sufficient statistical power for us to evaluate if there is any relationship between the day of the menstrual cycle, the day surgery was performed, and prognosis. This feasibility study indicates that these women should be followed up and the appropriate statistical studies should be done. PMID- 8479197 TI - Photo detection of carcinoma of the colon in a rat model: a pilot study. AB - Photodynamic sensitizers are light-absorbing chemicals that cause photoreactions in biologic systems when exposed to light of the proper wave-length. Dihematoporphyrin ethers (DHE) are the active porphyrin derivatives most commonly used as a photosensitizer (Photofrin, QLT). DHE accumulates in tumor tissue and also fluoresces when light activated. A more reliable and less costly screening method for early detection and treatment of colon cancer is needed. The present study was designed to induce adenocarcinoma of the colon in rats with 1,2 dimethylhydrazine (DMH) and attempt to identify tumors early in their evolution by DHE fluorescence. Forty rats were injected with 20 mg/kg of DMH at weekly intervals until sacrifice. Photofrin (3 mg/kg) was injected through the tail vein in each prior to sacrifice. Eight colonic specimens contained invasive adenocarcinoma, seven of which fluoresced when exposed to a Woods lamp. Carcinoma in situ was identified in two specimens by fluorescence, and one fluorescent specimen contained dysplasia. PMID- 8479198 TI - Selected benefits of thoracotomy and chemotherapy for sarcoma metastatic to the lung. AB - To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy. Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung. PMID- 8479199 TI - Resection margin in patients with gastric cancer associated with esophageal invasion: clinicopathological study. AB - We investigated the correlations between resection margin involvement by carcinoma and a number of clinicopathological features in patients with gastric cancer and esophageal invasion. From January 1968 to December 1988, 1,040 patients with carcinoma of the stomach underwent gastric resection. Thirty-nine patients had tumor infiltration of the esophagus on histological examination of the resected specimens. The patients were divided into two groups on microscopic examination: those in whom the resection margin was less than 5 mm wide, and those in whom it exceeded 5 mm microscopically. There were 6 and 33 patients in the narrow and wide margin groups, respectively. There were statistically significant differences in tumor size, depth of cancer invasion, and macroscopic appearance between the two groups. The risk of resection margin involvement was high in tumors with the following features: large Borrmann type 4 tumor (macroscopic appearance and size) and infiltrative carcinoma (depth of invasion). PMID- 8479200 TI - Limb-sparing treatment with surgery and intraoperative radiotherapy (IORT) for a second local recurrence of myxoid liposarcoma in the popliteal region, after previous surgery and high-dose radiation. AB - A 46-year-old man with a second local recurrence of a myxoid liposarcoma in the fossa poplitea, after surgery and high-dose external beam radiotherapy, was successfully treated by a limb-sparing procedure combining marginal excision, intraoperative radiotherapy and reconstructive surgery. After a 48-month follow up, there was no evidence of disease, and the function of the leg and knee was normal. PMID- 8479201 TI - Inventory of plants used in traditional medicine in Somalia. IV. Plants of the families Passifloraceae-Zygophyllaceae. AB - Thirty-seven plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects. Three plants which should have been included in Part I of the series have been added and some corrections to that paper have been made. With these additions the series comprises 180 different plant species, distributed in 59 plant families. PMID- 8479202 TI - Plants used in Guatemala for the treatment of gastrointestinal disorders. 3. Confirmation of activity against enterobacteria of 16 plants. AB - Ethnobotanical surveys and literature review identified 408 plants used in Guatemala for the treatment of gastrointestinal disorders. The screening of 84 showed that 34 inhibit one or more enterobacteria; 16 of these were selected for further investigation. Extracts were obtained with three solvents of different polarity (n-hexane, acetone and alcohol) and the in vitro activity was demonstrated against enteropathogenic Escherichia coli, Salmonella enteritidis and Shigella flexneri. The activity of nine ethanolic extracts against enterobacteria, particularly Acalypha guatemalensis, Diphysa robinioides, Lippia dulcis, Psidium guajava and Spondias purpurea was confirmed. The plants with antibacterial activity are discussed. PMID- 8479203 TI - Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. AB - Mutagenic and antimutagenic activities of extracts and chromatographic fractions of Uncaria tomentosa bark are reported. The plant extracts and fractions show no mutagenic effect in different strains of Salmonella typhimurium with and without metabolic activation. However, the plant extracts and fractions show a protective antimutagenic effect in vitro against photomutagenesis induced by 8-methoxy psoralen (8-MOP) plus UVA in S. typhimurium TA 102. A decoction of U. tomentosa ingested daily for 15 days by a smoker decreased the mutagenicity induced in S. typhimurium TA98 and TA100 by the subject's urine. PMID- 8479204 TI - Toxic effects of crude root extract of Plumbago rosea (Rakta chitraka) on mice and rats. AB - The ethanolic root extract of Plumbago rosea (Plumbaginaceae) was studied for acute toxicity in mice and subacute toxicity in rats. The 24 h LD50 values of the extract in mice were 239.88 mg and 1148.15 mg/kg b.wt. for intraperitoneal and oral routes, respectively. Oral administration of doses above 1250 mg/kg produced severe diarrhea. In subacute toxicity studies no mortality was observed when 50 mg/kg of the extract was injected i.p. daily for 30 days; however, there was no weight gain in the treated rats. Significant reduction in the weights of liver, kidney, thymus and testes was observed in the male rats, while the spleen weight showed a significant increase from control. The females showed a significant loss in thymus weight and a gain in the weight of the uterus, but the liver and spleen did not show any weight change from the control. There was a significant increase in total WBC and neutrophil counts as well as in the levels of serum alkaline phosphatase and alanine transaminase (ALT) in both sexes. Similarly, the liver alkaline phosphatase level was significantly higher than control, but a significant reduction was observed in the DNA, RNA and total proteins. Thus, a higher drug dose (total dose of 15 g/kg b.wt.) was tolerated in fractionated administration, but it had a growth inhibitory effect in both sexes. The males appear to be more susceptible than females when individual organs are considered. PMID- 8479205 TI - Pulmonary complications of orthotopic liver transplantation. AB - We retrospectively reviewed the pulmonary complications and associated morbidity and mortality of 44 consecutive patients who underwent 52 orthotopic liver transplantations (OLTs) at the Mayo Clinic during 1987. All survivors participated in follow-up for 1 year after OLT. Of the five deaths in the study group, three were associated with pulmonary infections. On postoperative chest roentgenograms, 24 cases of pulmonary infiltrates were noted; 12 were caused by infections. Ten opportunistic pulmonary infections developed in nine patients: four cytomegalovirus, three Pneumocystis carinii pneumonia, and one each of Cryptococcus, Aspergillus, and Candida. All except one of the opportunistic infections were diagnosed after the sixth postoperative week. Fiberoptic bronchoscopy was helpful for diagnosing opportunistic pulmonary infections in six patients. One Aspergillus pulmonary infection was diagnosed by transthoracic needle aspiration. Bacterial pneumonia occurred in five patients. Preoperative pulmonary function tests, performed in 40 patients, revealed a restrictive ventilatory defect in 28% and impaired gas transfer in 52%. Pleural effusion was present in 18% of patients preoperatively and in 77% during the first week after OLT. Preoperative severity of liver disease and results of arterial blood gas determinations, pulmonary function tests, and chest roentgenography were not associated with postoperative mortality and pulmonary infections. Infectious and noninfectious pulmonary complications are common in liver transplant recipients. Attempts to decrease the frequency and severity of pulmonary complications by early diagnosis and effective treatment may diminish the morbidity and mortality associated with OLT. PMID- 8479206 TI - Medical mythology: Hygeia. PMID- 8479207 TI - Posttraumatic cervical dystonia. AB - Posttraumatic cervical dystonia has been described as a distinct syndrome with some similarities to idiopathic nontraumatic cervical dystonia (torticollis). We describe five patients in whom cervical dystonia developed immediately after relatively mild trauma to the neck. Four of the five patients had persistent contractions of all cervical muscles including the trapezius muscles, which almost completely prevented motion of the neck and resulted in muscle hypertrophy. The condition persisted unabated in all patients for the entire period of follow-up (duration, 1 1/2 to 3 years). Pharmaceutical interventions, which had been used previously for idiopathic nontraumatic cervical dystonia, failed to benefit these patients. Two patients who received injections of botulinum toxin had no more than mild benefit. Selective denervation was inapplicable because of the widespread involvement of all cervical muscles in all but one patient. Physical therapy was essentially ineffective. Because of the unusual features and possible medicolegal setting, clinicians may tend to diagnose this condition as a psychogenic disorder or litigation-oriented behavior. The clinical picture, however, is consistent with an organic dystonia that may render the patient functionally and occupationally disabled. PMID- 8479209 TI - Likelihood of malignant disease for various categories of mammographically detected, nonpalpable breast lesions. AB - To determine the likelihood of malignant disease for mammographically detected, nonpalpable breast lesions, we defined 11 morphologic categories and retrospectively reviewed the mammograms in 859 cases in which biopsy was performed after a wire localization procedure at our institution during 1989 and 1990. Within each category, the total number of lesions and the percentage of cases with a surgical pathologic diagnosis of malignant involvement were as follows: benign calcification, 25 (0% malignant); indeterminate calcification, 200 (22%); malignant calcification, 39 (92%); smooth mass, 84 (1%); irregular mass, 337 (40%); architectural distortion, 45 (47%); asymmetric breast tissue, 37 (3%, or 1 case of asymmetrically prominent ducts); smooth mass with calcification, 3 (0%); irregular mass with calcification, 68 (66%); architectural distortion with calcification, 14 (57%); and asymmetric breast tissue with calcification, 7 (29%). The overall rate of malignant involvement for the 859 cases was 34%. If follow-up examinations rather than biopsies had been done for the lesions categorized as benign calcification, smooth mass, smooth mass with calcification, and asymmetric breast tissue (excluding asymmetrically prominent ducts), the overall positive predictive value would have increased from 34 to 41%, and 148 biopsies would have been deferred (17% of all biopsies). If morphologic criteria are applied to the evaluation of mammographically detected, nonpalpable lesions, the rate of malignant disease at biopsy may reach 40%. This rate correlates with that in recent large series. PMID- 8479208 TI - Long-term follow-up of young patients with chronic hereditary or idiopathic pancreatitis. AB - We conducted a retrospective study of patients younger than 20 years of age who had a diagnosis of chronic pancreatitis and underwent assessment at the Mayo Clinic between 1960 and 1990. Those with a known etiologic factor for the pancreatitis (such as a virus, trauma, alcohol, or hyperlipidemia) were excluded from the study. We compared the clinical course of the 42 patients who had hereditary pancreatitis (HP)--defined as at least two family members affected by the condition--with that of the 28 patients who had idiopathic pancreatitis (IP). The mean age at initial assessment was 7 years for those with HP and 12 years for those with IP. All patients in both groups had abdominal pain. Vomiting was more frequent in patients with HP than in those with IP; otherwise the initial symptoms were similar in both groups. Patients with HP, however, had more complications, including pseudocysts (seven patients), steatorrhea (four), ascites (three), portal hypertension (two), and diabetes (one), than did patients with IP (one each had diabetes, steatorrhea, and a pseudocyst). Complications or pain necessitated surgical intervention in 23 of 42 patients with HP versus 4 of 28 patients with IP. Overall in comparison with IP, HP seems to be a more severe variant of chronic pancreatitis, inasmuch as it is associated with more frequent complications and need for surgical intervention. PMID- 8479210 TI - Falling off the pedestal: what is happening to the traditional doctor-patient relationship? PMID- 8479212 TI - Pulmonary manifestations of extrathoracic malignant lesions. AB - Two of the most common thoracic manifestations of extrapulmonary malignant tumors are thoracic metastatic lesions and pulmonary thromboembolism. Recognition of the broad array of patterns of pulmonary metastatic involvement is essential for optimal management of oncology patients. In addition to the "typical" pattern of multiple bilateral nodules, patients may have solitary nodules, reticulonodular infiltrates, hilar and mediastinal adenopathy, endobronchial obstruction, pleural disease, or even normal roentgenographic findings. An awareness of the association between cancer and pulmonary thromboembolism is also valuable. The mechanisms potentially responsible for the thrombotic events associated with malignant disease are discussed, and diagnostic issues are reviewed. PMID- 8479211 TI - Aneurysm of an aberrant right subclavian artery: case report and review of the literature. AB - In this article, we describe a case of a surgically treated aneurysm of an aberrant right subclavian artery. The historical literature to date is summarized, as are the key concepts relative to the anatomy, embryology, diagnosis, and treatment of this uncommonly occurring entity. Although the topic might be expected to be of concern to only a few specialists, all physicians should be aware that a patient with an enlarging aneurysm of an aberrant subclavian artery may experience dyspnea, dysphagia, or sudden collapse from rupture as the initial manifestations. An asymptomatic patient may have a mediastinal mass detected by roentgenography. The diagnosis may be confirmed with computed tomography or magnetic resonance imaging. As with most aneurysms, surgical treatment is recommended, and the benefit-to-risk analysis depends on individual case factors. PMID- 8479213 TI - Insufficiency-type stress fracture. PMID- 8479215 TI - Perioperative indications for red blood cell transfusion--has the pendulum swung too far? PMID- 8479214 TI - Palsies of the trochlear nerve: diagnosis and localization--recent concepts. AB - In this review, the anatomy of the trochlear nerve, the diagnosis of palsies of the trochlear nerve, and the localization of lesions of the trochlear nerve are discussed. Paresis of the superior oblique muscle is often not evident on duction testing; therefore, subjective diplopia testing with use of a Maddox rod is often necessary. The torsional component of the deviation may be evaluated by double Maddox rod testing. Palsies of the trochlear nerve must be distinguished from other causes of vertical diplopia, such as oculomotor palsy, skew deviation, myasthenia gravis, and Graves' ophthalmopathy. Trauma is the most common cause of isolated, unilateral or bilateral, acquired palsies of the trochlear nerve when a cause can be determined. The localization of lesions of the trochlear nerve to the nucleus or fascicles (or both), subarachnoid space, cavernous sinus and superior orbital fissure, or orbit depends on the associated damage to neighboring neurologic structures. Myokymia of the superior oblique muscle is usually idiopathic and benign but may rarely be an isolated manifestation of tectal disease. PMID- 8479216 TI - [Thyroid ophthalmopathy: clinical and tomographic study]. AB - BACKGROUND: To evaluate exophthalmos by Hertel exophthalmometer (HE) compared to computed tomography (CT), and extraocular muscle width on CT and its relation with the clinical course in patients with thyroidal ophthalmopathy. METHODS: On reviewed 118 orbits from 59 patients (50 women, mean age 40.6 y., range 12-84) who suffered a thyroidal ophthalmopathy (Graves' disease, n = 57; Hashimoto's thyroiditis, n = 2). Muscle width was evaluated using coronal and mid-axial scans in all cases. Medial rectus (MR) width was analysed by Hallin and Feldon technique. RESULTS: Exophthalmos by HE was 22.5 +/- 2.5 and 23.2 +/- 3.2 mm (right-RE/left eye-LE), and CT 20.8 +/- 3.2 and 20.9 +/- 2.9 mm (p < 0.00001, r = 0.72 and 0.65, respectively). MR width on mid-axial scan was 4.1 +/- 1.6 and 4.2 +/- 1.5 mm (RE/LE). On coronal scans, MR was the muscle more often enlarged followed by superior, inferior and lateral rectus. CONCLUSIONS: Exophthalmos measured by HE was greater than by CT-measured one, but with a good correlation. Muscle were not equally affected, being MR the most frequently enlarged. MR-width was not related to duration and severity of disease. PMID- 8479217 TI - [Effect of a highly hypocaloric diet on the control of morbid obesity in the short and the long term]. AB - BACKGROUND: The ponderal evolution and biochemical parameters during the in patient administration of a highly hypocaloric and high protein diet (VLCD) were evaluated. The efficacy at medium term of this treatment was determined and the possible determining factors of the ponderal evolution were analysed. METHODS: A VLCD was administered to 20 women with morbid obesity during 21 days. The modifications of the biochemical parameters were determined during admission. The ponderal evolution was studied during hospitalization and during 9 months of out patient follow up. The prognostic factors of ponderal evolution analyzed were: age, attempts to lose weight, familiar history of obesity, maximum weight attained, weight and index of body mass (IBM) at study initiation and admission, loss of weight during admission and the number of out patient controls. RESULTS: During hospitalization, a mean loss of 7.0-1.9 kg, a significant decrease in glycemia, cholesterol, triglycerides, lymphocytes and blood pressure were observed. It was found that ponderal loss at 3 and 6 months may be predicted by IBM upon initiation of the study. At 9 months weight was lower than at initiation of hospitalization but not than at discharge (p < 0.001). Weight upon initiation of the study and the maximum reached explain the weight at 9 months in 82.5% of the cases. CONCLUSIONS: Highly hypocaloric and high protein diets lead to a significant weight loss which is maintained at medium term and an improvement in the factors of cardiovascular risk are observed. Of the factors evaluated, only the grade of obesity significantly influences ponderal evolution. PMID- 8479218 TI - [Immunotherapy of leukemia]. PMID- 8479219 TI - [Spain and research in applied biology in the European community: present and future]. PMID- 8479220 TI - [Epidemiology of abdominal aorta aneurysms]. PMID- 8479221 TI - [Mild renal insufficiency in a 70-year-old male with bladder carcinoma]. PMID- 8479222 TI - [Molecular epidemiology]. PMID- 8479223 TI - [Mycobacterium gordonae isolation in samples from bronchial aspirates and its practical implications]. PMID- 8479224 TI - [Evaluation of a style of classes and seminars]. PMID- 8479225 TI - [Visceral leishmaniasis associated with disseminated intravascular coagulation. Report of 2 cases]. PMID- 8479226 TI - [Pre- and post-vaccination markers in health personnel]. PMID- 8479227 TI - [Retrospective evaluation of the effectiveness of the BCG vaccination program in neonates in Barcelona]. PMID- 8479228 TI - [Breast cancer, tamoxifen, and uterus]. PMID- 8479229 TI - [Brigantium study. Cardiovascular risk factors in childhood and adolescence in a rural area of Galicia]. AB - BACKGROUND: The aim of this study was to determine the levels of certain factors of cardiovascular risk in children and adolescents in rural areas of Gallicia. METHODS: One thousand eight children between the ages of 6 and 15 years selected from three primary schools were studied. Weight, height, blood pressure, serum levels of cholesterol and self admitted consumption of tobacco were determined in each participant. RESULTS: The patterns of body mass, blood pressure and total cholesterol selected to age and sex are very similar to those observed in a great deal of the Spanish and foreign studies. However, the absolute values do not necessarily coincide. The children studied were more obese than those reported in other studies carried out in the rest of Spain with similar values of systolic blood pressure and lower cholesterol levels. The levels of cholesterol in this study were within the range observed in other Western countries, lower than those found in other parts of Spain but much higher than the ideal quantities recommended by the WHO. Blood pressure was similar to that of a recent meta analysis of Spanish studies but much higher than that observed in the Second American Task Force Study. With regard to the use of tobacco, this population demonstrated lower prevalences to those of other Spanish populations. From the age of 14 the consumption of cigarettes greatly increases, especially in boys. CONCLUSIONS: Obesity and blood pressure appear to be a more important potential problem than cholesterol among the cardiovascular risk factors considered in the children studied in comparison with populations of a similar age. If prevention plans on the use of tobacco are foreseen in Spain, they should be made before the age of 14 when an important number of children already smoke or have tried cigarettes. PMID- 8479230 TI - [Clinical effectiveness and tolerance of acarbose in the treatment of insulin dependent diabetic patients (type I)]. AB - BACKGROUND: Acarbose is a reversible inhibitor of the intestinal alpha glucosidases, the oral administration of which delays or diminishes the postprandial increase of glucose and insulin. METHODS: A multicentric double blind clinical trial (11 centers), controlled versus placebo, crossed and randomized, was carried out with 137 insulin-dependent diabetic type I patients treated with diet and insulin. During the first 3 months of the trial the patients received placebo or acarbose randomly. Following one month of wash out with placebo the patients received the inverse medication for 3 more months. During the first month of each phase the patients were given 50 mg three times per day of acarbose or placebo and the two following moths received 100 mg x 3/day. RESULTS: Upon comparison of the two treatments significant statistical differences were found in HbA1 (p = 0.0005) and in postprandial glycemia (p = 0.007). There were differences, although not statistically significant, in the amounts of triglycerides, cholesterol and fasting glycemia. One hundred and two patients referred adverse events, most being gastrointestinal (flatulence, meteorism). CONCLUSIONS: Acarbose may be useful in the treatment of insulin dependent diabetic type I patients treated with insulin and diet since it reduces the levels significantly of HbA1 and postprandial glucose. PMID- 8479231 TI - [Multicenter study of HTLV-I and HTLV-II infection in Spain. Spanish Group for the Study of HTLV-II/II Infection]. AB - BACKGROUND: Human T-lymphotropic viruses type I (HTLV-I) and type II (HTLV-II) infections have been related to lymphoproliferative disorders and subacute neurological diseases. Screening blood donors for specific HTLV-I/II antibody has been implemented in Japan, United States, and recently in France. Should be it recommended in Spain? METHODS: Antibodies to HTLV-I/II were investigated in sera from 7,884 individuals living in Spain. They were classified in four major groups: 1) subjects at high-risk for retrovirus infection, as drug addicts, homosexuals, and polytransfused individuals (n = 4,740), 2) patients suffering HTLV-like symptoms (n = 760), 3) immigrants from or travellers to endemic areas (n = 1,427), and 4) blood donors (n = 957). RESULTS: Eighteen (0.22%) subjects were HTLV-I positive and 11 (0.12%) were classified as HTLV-II reactive. Five (71.5%) of 7 immigrants or travelers to endemic areas reacting against HTLV were typed as HTLV-I. Six (60%) of 10 drug addicts HTLV-reactive were typed as HTLV-II carriers. CONCLUSIONS: Both HTLV-I and HTLV-II infections are present in Spain, although in a low rate and mostly restricted to drug addicts (HTLV-II), and people coming from endemic regions (HTLV-I). All tested blood donors were negative. In this view, HTLV-I/II screening in Spanish blood banks seems to be non urgent, although alternative strategies should be considered. PMID- 8479232 TI - [Tobacco and adolescents: better safe than sorry]. PMID- 8479233 TI - [The illness perceived by the patient and the clinical method. A thought from the general medicine point of view]. PMID- 8479235 TI - [Drug-induced fever]. PMID- 8479234 TI - [Tobacco and adolescents: influence of the personal environment]. AB - BACKGROUND: The initiation of the smoking habit is related both with personal and environmental characteristics. Several authors have described the association of the smoking habit of parents, older siblings, and friends with the use of tobacco by teens. METHODS: This study is based on a cross-sectional survey to 6th and 7th grade students in Barcelona (Spain). RESULTS: This study confirms there is a growing proportion of smokers among teens when their parents, siblings and friend smoke. Children whose parents have quit smoking behave as the sons of parents who have never smoked, and smoke much less than the children of current smokers. When parents do not smoke, having siblings and friends who smoke increases the frequency of smoking from 0.2 to 3.4%, a 17-fold increase. CONCLUSIONS: Current smoking and future smoking intention are related with the number of smokers in the teen environment. These results support preventive programs in schools that include activities to resist external pressures to smoke. It also suggests that helping young adult smokers quit contributes not only to their own health, but also prevents the initiation of smoking among teens in their environment. PMID- 8479236 TI - [Campylobacter jejuni bacteremia in patients infected with HIV]. PMID- 8479237 TI - [Subcutaneous venous reservoirs]. PMID- 8479238 TI - [Hypoglycemic coma and advanced grade atrioventricular block with episodes of torsades de pointes]. PMID- 8479239 TI - [Changes in the thyroid hormone profile following the prophylactic administration of mefloquine]. PMID- 8479240 TI - [One year's experience with "home hospitalization" in the rural area]. PMID- 8479241 TI - [Preventive interruption of the administration of HA-1A monoclonal antibody against endotoxin]. PMID- 8479242 TI - Generation of early afterdepolarization in mouse ventricular fibers at long cycle length. AB - Early afterdepolarization (EAD) was studied in ventricular fibers of mouse heart. EAD could be occasionally induced under long cycle length of superfusion with Tyrode's solution (containing 3.0 or 5.0 mM KCl) at long cycle length. Three types of EAD were found: a second plateau with a prominence, a single triggered burst and a train of triggered bursts. Take-off potential of the first triggered burst or of the prominence varied from -40 to -60 mV. The triggered bursts in the third type often stopped at -35 to -45 mV level forming a very long second plateau before it completely repolarized. Changing abruptly from a long cycle length to a short one lead to a transient EAD induction. It is suggested that EAD in ventricular fiber in mouse heart shared the characteristics of that in atrial fibers, although it was very difficult to induce and was not very reproducible. PMID- 8479243 TI - The electrophysiological effects of alcoholized rhubarb solution in feline heart in vivo. AB - The effects of Chinese medicine, alcoholized rhubarb, on cardiac electrophysiology and contractile force were studied by using monophasic action potential (MAP) techniques with an improved pressure-electrical transducer epicardial electrode and/or an endocardial pressure-contact electrode catheter in 27 feline hearts in vivo. The results of the experiments were as follows: 1) Alcoholized rhubarb solution (1.5 g/kg) caused a greater increase in the MAP amplitude (from 18.8 +/- 0.62 mV to 26.7 +/- 3.87 mV, p < 0.01), in the MAP maximum rate of rise of phase 0 (from 1.7 +/- 0.13 V/sec to 2.6 +/- 0.43, p < 0.01), and in the MAP duration at 50% and 90% repolarization (from 194.3 +/- 14.00 msec to 216.3 +/- 6.30 msec and from 238.8 +/- 21.41 msec to 280.5 +/- 14.68 msec, respectively, p < 0.01), and a decrease in the heart rate (from 130.8 +/- 12.10 bpm to 110.8 +/- 10.35 bpm, p < 0.01) in the epicardial monophasic action potentials after rhubarb solution administration for 1 min. 2) The ventricular contractile force of the feline heart in vivo was also significantly increased (11.1 +/- 0.52 g to 14.0 +/- 1.41 g, p < 0.01) by rhubarb solution. 3) A dose-dependent relation of alcoholized rhubarb solution was found and indicated that lower doses (1.0-1.5 g/kg) had an excitatory effect, while a higher dose (2.0 g/kg) had inhibitory or toxic effects on the intact feline heart. The present study provides evidence that Chinese rhubarb solution has electrophysiological effects on the feline heart in vivo. PMID- 8479244 TI - A study on the development of nociceptive responses in pre- and postweanling rats: the tail electric stimulation test as a suitable methodology. AB - The development of nociceptive responses to the tail electric stimulation test was investigated. Male Wistar albino rats were used for studies on adult and pre- and postweanling rats of 20 and 25 days of age, respectively. The thresholds for the motor response (tail withdrawal), vocalization during stimulus and vocalization afterdischarge were assessed. These responses are considered to be integrated at spinal, medulla oblongata and diencephalon-rhinencephalon levels, respectively. Adult animals showed significantly higher thresholds for the three responses when compared to the neonates, while 25-day old rats showed significantly higher thresholds for the vocalization afterdischarge than the 20 day old pups. Although the effect of age cannot be ruled out, these latter results might indicate that the weaning process is critical in the development of the mechanisms related to the emotional/affective component of pain. The results also indicate the suitability of the nociceptive test employed for these kinds of studies. PMID- 8479245 TI - Selective inhibition of endothelium-dependent relaxation by sympathectomy in rabbit carotid artery rings in vitro. AB - The influence of cervical and periarterial sympathectomy on endothelium-dependent relaxation of the rabbit common carotid artery was studied in vitro. Noradrenaline, serotonin, acetylcholine and papaverine concentration-response curves of sympathectomized and control rabbit common carotid artery rings were recorded and analyzed and effects of endothelium removal were investigated. Endothelium-dependent relaxation was selectively and significantly inhibited in 3 weeks postsympathectomy arterial preparations. Alterations in acetylcholine receptors of endothelial cells, decrease in endothelium-derived relaxing factor synthesis, or desensitization of medial muscular cells to endothelium-derived relaxing factor are hypothetical causes of this phenomenon. PMID- 8479247 TI - Telemetry. PMID- 8479246 TI - The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam. II. Influence of hydrogel-borne propylene glycol and skin pretreatment with lauryl alcohol. AB - Enhancers of the percutaneous diffusion of clonazepam in the isolated single-pass perfused rabbit ear were evaluated and included propylene glycol (PG), polyethylene glycols (PEGs) of different molecular weight, as well as skin pretreatment with lauryl alcohol (LA). PG caused a concentration-dependent increase in the diffusion of clonazepam, due partly to the increased solubility of the active principle in the hydrogel. PEGs of molecular weight up to 3,000 Daltons added to the PG hydrogel showed a simple additive effect on percutaneous diffusion enhancement induced by PG. Transdermal delivery of clonazepam also increased as a function of exposure time following pretreatment with LA. PMID- 8479248 TI - A foreshortened method of measuring liquid gastric emptying in normal volunteers. AB - The purpose of this study was to compare the cumulative fraction absorbed-time profile method of paracetamol with the shorter proportional area under the curve method of paracetamol by pretreating normal volunteers with cisapride, codeine and metoclopramide with and without neostigmine. Both methods are sensitive and comparable in defining early phase liquid gastric emptying, with the proportional area under the curve method having the advantage of providing the relevant information with a two-hour study period. PMID- 8479249 TI - Alternatives to assess rate of absorption. PMID- 8479250 TI - BN-50739: a PAF antagonist and limitation of myocardial infarct size. AB - Anesthetized rats were subjected to coronary artery ligation (CAL) for 72 h and infarct size was measured macroscopically using TTC staining. Systolic blood pressure and ECG were monitored. BN-50739 (5 mg/kg i.p.) decreased the myocardial infarct size in rats. It prevented the loss of R wave, an electrophysiological measure of ischemic injury in this model. In addition, BN-50739 markedly reduced serum malondialdehyde levels elevated as a consequence of CAL. It is speculated that being a PAF antagonist, BN-50739 decreased lipid peroxidation, perhaps by inhibiting migration of PMN cells to the site of ischemic injury through the limited collateral flow available in rat myocardium, and consequently may have reduced the generation of oxygen reactive species. This may be responsible for its beneficial effect in limiting infarct size. PMID- 8479251 TI - [Annus horribilis for MFR. The junior program is a lottery involving millions]. PMID- 8479252 TI - [Bad arguments for the grades!]. PMID- 8479253 TI - [How to deal with drunk drivers]. PMID- 8479254 TI - [The tobacco legislation must be more stringent]. PMID- 8479255 TI - [The debate on equality is important]. PMID- 8479256 TI - [Variation ECG. New thinking on diagnostics in electrophysiology]. PMID- 8479257 TI - [Nitric oxide--more than a vasodilator]. AB - Endothelium-dependent vasodilation is mediated by nitric oxide (NO), which is synthesised from the amino acid arginine. The enzymes involved are present in several cell types, and NO has important regulatory functions in many of the organ systems of the body. NO seems to be of importance in the regulation of blood pressure, neuronal activity in the peripheral and central nervous systems, in ventilation perfusion-matching in the lungs, and in immune defense. Although the clinical use of nitroglycerin is more than a century old its mechanism of action, the liberation of NO, has only recently been elucidated. Endogenous nitric oxide synthesis inhibitors have been identified, and both these and NO itself are being examined in clinical trials. PMID- 8479258 TI - [Public information about ionizing radiation is unsatisfactory]. PMID- 8479259 TI - [Neglected research of anorexia and bulimia]. PMID- 8479260 TI - [The greatest progress in enteral nutrition. Percutaneous endoscopic gastrostomy is used more and more]. PMID- 8479261 TI - [Nutrition via gastrostomy. Low frequency of complications with PEG]. PMID- 8479262 TI - [Myocarditis after Borrelia infection? Case reports]. PMID- 8479264 TI - [Need for thrombocytes among hematologic patients. Medical and economic aspects]. PMID- 8479263 TI - [Screenings methods for microalbuminuria. Measuring rods are sufficiently exact]. PMID- 8479265 TI - [The Swedish hostage in Bagdad in 1990. Early stress reactions and psychological support]. PMID- 8479266 TI - [Positive effects of the guarantee of care. Markedly reduced waiting lists for treatment]. PMID- 8479267 TI - [Prontosil. A German coloring agent which became the current sulfa]. PMID- 8479268 TI - [How to grade a good physician?]. PMID- 8479269 TI - [Surplus of physicians--parallels with the 30's]. PMID- 8479270 TI - [Open care environment--nothing granted for pediatric surgeons only!]. PMID- 8479271 TI - [Reconsideration of and professorship in psychoanalysis are needed]. PMID- 8479272 TI - [Cardiopulmonary resuscitation. New discoveries and recommendations]. PMID- 8479273 TI - [A longitudinal study of schoolchildren. Rehabilitate early in backache/headache]. PMID- 8479274 TI - [Mental stress and heart disease. Is there a connection?]. PMID- 8479275 TI - [Diethylstilbestrol. Tragic late effect after prenatal exposure]. PMID- 8479276 TI - [Rubber allergy. An increasing problem with special risk for children with myelocele]. PMID- 8479277 TI - [HIV-positive Africans spread the infection. Many of them ignore the rules of protection against the infection]. PMID- 8479278 TI - Distribution of GAP-43 (B50/F1) mRNA in the adult rat brain by in situ hybridization using an alkaline phosphatase labeled probe. AB - GAP-43 (B-50,F1, pp46) is a calmodulin binding protein which is specific to the nervous system and also a substrate for the protein kinase C. Furthermore an enrichment of this protein in the growth cone and developmental brain indicate that this protein is related to nerve development, regeneration, and outgrowth. While its level dramatically decreases after the completion of synaptogenesis, the protein is still to some extent continuously expressed in certain regions of the mature brain. In order to clarify GAP-43 localization in mature normal rats, we investigated the distribution of GAP-43 mRNA in the rat central nervous system by using a non-radioisotopic in situ hybridization histochemistry. This method demonstrated GAP-43 mRNA expressing cells with high resolution. GAP-43 mRNA was more abundant in the forebrain than in the lower brainstem. Intense hybridization signal was observed in the mitral cells of olfactory bulb, cerebral cortex, CA3 region of hippocampus, diagonal band, substantia nigra, raphe nuclei, locus coeruleus, and dorsal motor nucleus of vagus. Weak to moderate hybridization signals were also widely expressed in thalamus, hypothalamus, and midbrain. Moreover, most noradrenergic, adrenergic, serotonergic, histaminergic, and caudal part of dopaminergic cells exhibited an intense GAP-43 mRNA signal. Thus, GAP-43 mRNA is abundantly expressed under normal conditions in the brain and may play an important physiological role particularly in the forebrain and in monoaminergic neurons supporting the findings that GAP-43 could be implicated in plasticity and monoamine release. PMID- 8479279 TI - A comparison of microtubule assembly in brain extracts from young and old rats. AB - Microtubule assembly was examined in the high-speed supernatant from homogenates of young (2-4 months old) and old (more than 24 months old) rat brains and significant age-related differences in microtubule assembly were found in the absence of exogenous GTP. In extracts from young brains, the increase in absorbance at 350 nm, which reflects the assembly reaction, was characterized by three phases (lag, elongation, and steady state) superimposed on a slow continuous increase due to non-specific aggregation. However, assembly in extracts from old brains, was very sluggish, in some cases barely more rapid than the non-specific aggregation reaction. Two to three times as much protein was assembled into cold-labile microtubules in extracts from young brains than from old brains. When 1 mM GTP was included in the assembly solutions the patterns of assembly in extracts from young and old brains became similar, with about the same amount of protein assembled into cold-labile microtubules. The assembly of tubulin purified from rat brains showed no differences between young and old. Results showed that extracts from old brains contained a higher GTPase activity than extracts from young brains. The sluggish assembly in extracts from old brains could be due to a deficiency in GTP or an inefficient regeneration of GTP. PMID- 8479280 TI - Neural regulation of phenylethanolamine N-methyltransferase in vivo: transcriptional and translational changes. AB - The hypothesis that neural regulation of rat adrenal medullary phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) occurs through transcriptional control is examined by following temporal changes in PNMT mRNA expression using paradigms of acute and chronic reserpine treatment. Concommitant changes in PNMT activity and protein were also measured to determine if reserpine induced changes depend solely on gene activation. Further, changes in adrenal corticosterone were measured to examine whether mRNA and enzyme responses might be mediated via reserpine induced changes in ACTH, and hence, corticosterone. Steady-state levels of PNMT mRNA peaked at approximately 8-fold normal by 6 h after a single reserpine injection (10 mg/kg i.p.), and then declined to control values. With continued treatment, a second, slower rise occurred after three alternate day injections (approximately 3-fold basal levels). Enzyme activity and protein rose simultaneously but were attenuated in magnitude and time course by comparison to message. With both acute and chronic treatment, activity increased 2.0-fold, peaking at 12 h after a single dose of reserpine and again after four doses of the drug. Protein, as measured by immunotitration, was elevated 1.2-and 1.4-fold, respectively. Adrenal corticosterone rose approximately 8-fold at 6 h, declined slightly at 12 h, rose again, and remained elevated thereafter. Comparison of the time courses for the various indices demonstrated that the early parallel bursts in PNMT mRNA and corticosterone are consistent with an increase in transcriptional activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479281 TI - Effect of growth factors and cytokines on expression of amyloid beta protein precursor mRNAs in cultured neural cells. AB - We analyzed the effect of several growth factors and cytokines on the expression of amyloid beta protein precursor (APP) mRNAs in cultured mouse neuronal and glial cells. In neuronal cultures from embryonic day-15 brain. Northern blotting revealed that APP mRNAs increased by 1.3- to 2.6-fold when treated with nerve growth factor, basic fibroblast growth factor, interleukin 1, interleukin 2, interleukin 3, interleukin 6 or granulocyte-macrophage colony-stimulating factor but not with tumor necrosis factor alpha. An S1 nuclease protection assay revealed that the enhanced APP mRNA in neuronal cultures was exclusively APP695 mRNA. On the other hand, astrocyte-enriched cultures prepared from postnatal day 2 brain did not show any significant alteration among these factors. We conclude that certain growth factors and cytokines could enhance APP 695 mRNA expression in neurons in vitro. PMID- 8479282 TI - Cholinergic regulation of rat preproenkephalin RNA in the adrenal medulla. AB - Expression of the rat preproenkephalin (ppENK) gene involves transsynaptic cholinergic mechanisms. We evaluated the effects of cholinergic agonist treatments in vivo on the expression of adrenomedullary ppENK RNA. Cholinergic treatment with nicotinic + muscarinic receptor agonists resulted in a synergistic 100-fold rise in steady-state ppENK messenger RNA levels, but only a 30- to 35 fold rise in initiation of steady-state ppENK RNA transcripts. The levels of initiated ppENK steady-state RNA peaked at two days, whereas mature (1.45 kb) ppENK mRNA levels continued to rise, peaking at four days. This suggested that other transcriptional (attenuation or alternative splicing) or post transcriptional (RNA stabilization) regulatory mechanisms must be operative. As multiple ppENK RNA start sites exist, we examined how usage of multiple sites was altered by cholinergic treatments. The predominant start site changed from E2 in the basal state, to E4 after primary cholinergic stimulation, to E3 after re treatment. This represents novel example of differential usage of multiple RNA initiation start sites in vivo. Differences in initiated and mature transcripts are consistent with at least four mechanisms involved in control of cholinergic induced ppENK RNA expression: (i) simply new initiation of RNA transcripts, (ii) differential usage of the multiple RNA start sites, (iii) stabilization of mRNA transcripts, and (iv) attenuation and/or alternative RNA splicing of RNA transcripts. PMID- 8479283 TI - Colocalization of muscarinic acetylcholine receptors and protein kinase C gamma in rat parietal cortex. AB - The present investigation analyzes the cellular distribution of muscarinic acetylcholine receptors (mAChRs) and the gamma isoform of protein kinase C (PKC) in the rat parietal cortex employing the monoclonal antibodies M35 and 36G9, respectively. Muscarinic cholinoceptive neurons were most present in layers 2, 3 and 5, whereas most PKC gamma-positive cells were found in layers 2, 5 and 6. Under normal, non-stimulated conditions, approximately 58% of all muscarinic cholinoceptive neurons were immunoreactive for PKC gamma. Conversely, nearly all PKC gamma-positive neurons were M35-immunoreactive. Although both pyramidal and nonpyramidal neurons express the two types of protein, the pyramidal cell type represents the vast majority. Of all cortical neurons, the large (15-25 microns in diameter) muscarinic cholinoceptive pyramidal neurons in layer 5 express the gamma isoform of PKC most abundantly and most frequently. Approximately 96% of these cells are immunoreactive for PKC gamma. Stimulation of mAChRs by the cholinergic agonist carbachol resulted in a pronounced increase in the intensity of 36G9 immunoreactivity, which may suggest that the mAChRs are functionally linked to the colocalized PKC gamma. No change was found in the number of 36G9 immunoreactive neurons. In contrast, the number of immunocytochemically detectable muscarinic cholinoceptive neurons increased by approximately 38% after carbachol stimulation. The high degree of codistribution in cortical neurons of both transduction proteins suggests a considerable cholinergic impact upon the regulation of PKC gamma, a candidate key enzyme in cortical learning and memory mechanisms. PMID- 8479284 TI - Increases in sulphated glycoprotein-2 mRNA levels in the rat brain after transient forebrain ischemia or partial mesodiencephalic hemitransection. AB - Sulphated glycoprotein-2, thought to be involved in programmed cell death in peripheral organs, has been detected at increased levels in brain degenerative states. In this paper we have investigated the regional and cellular expression of this protein during development of brain lesion. With this aim sulphated glycoprotein-2 mRNA levels were studied in models of ischemic (transient forebrain ischemia) or mechanical (partial mesodiencephalic hemitransection) brain injuries using in situ hybridization histochemistry. Marked increases in sulphated glycoprotein-2 mRNA were observed in lesioned brains in both models. In addition, we report a shift in the regional distribution of positive cells in both lesion models 1-7 days post-lesion. After transient forebrain ischemia, sulphated glycoprotein-2 mRNA increases were always localized in selectively vulnerable regions (caudate-putamen, hippocampal formation), showing a temporal change in the pattern of intraregional distribution from less to more lesioned parts. In the case of mechanical lesion at 1 day, increased labelling had a widespread distribution on the lesioned side and was also observed on the intact side near the midline. In contrast, at 7 days increased labelling was restricted to regions directly lesioned (either areas whose input and/or output connections were severed by the transection or areas which were directly affected by the mechanical lesion). Analysis at the cellular level revealed that at both time intervals and in both lesion models most cell bodies overlain by dense clusters of specific grains were non-neuronal cells. The distribution patterns and their change over time suggest that at least some of these cells are inflammatory and phagocytic cells. The majority of degenerating neuronal cells after ischemia did not show increased levels of sulphated glycoprotein-2 mRNA. However, seven days after hemitransection and at all time intervals after transient ischemia, some cells clearly identifiable as neurons exhibited increased sulphated glycoprotein 2 mRNA levels. PMID- 8479285 TI - Memory processing and apamin induce immediate early gene expression in mouse brain. AB - The present study analyses the effects of learning on the spatial pattern and the time-course of changes of immediate early gene messenger RNA's (c-fos and c-jun) in mouse brain produced by training in an appetitive bar-pressing task. Activation of c-fos and c-jun after training is strictly located in the hippocampal formation and is learning-dependent. Levels of both proto-oncogene mRNAs in the trained group were 4 to 5 times higher than in the sham-conditioned group. Injections of apamin, a bee venom neurotoxin that selectively blocks a class of Ca(2+)-activated K+ channels and improves learning and memory retention, produced as compared to untrained animals a 3- to 5-fold increase of expression of c-fos and c-jun with the same pattern as that observed in the trained animals. Post-training injection of 0.2 mg/kg apamin enhanced 1.4-fold the expression of both immediate early genes in CA1, CA3 and dentate gyrus as compared to trained saline-injected mice. All these results suggest that apamin-induced increase of immediate early gene expression might be related to the apamin-induced facilitation of learning. PMID- 8479286 TI - Non convulsive spike-wave discharges do not induce Fos in cerebro-cortical neurons. AB - Immunohistochemical localisation of Fos was used as a marker of neuronal activity to demonstrate neurons active during non-convulsive spike-wave epilepsy. Fos positive neurons in cortex and several subcortical areas were counted. In undisturbed animals. Fos counts were not related to spike-wave in any region. With the electroencephalographic (EEG) recording procedure. Fos induction occurred in all regions, even after habituation. However, in central cortex, counts were found to be inversely related to spike-wave duration. This suggests that neuronal activity is not increased during spike-wave and that the central cortex in these animals is less responsive to arousal than in non-epileptic animals. PMID- 8479287 TI - Dopamine transporter mRNA expression is intense in rat midbrain neurons and modest outside midbrain. AB - Dopamine transporter mRNA expression in individual neurons from the substantia nigra pars compacta. 'All' area, arcuate nucleus of the hypothalamus, retina, and olfactory bulb was assessed by in situ hybridization. High levels of expression were noted over individual neurons in midbrain nuclei; much lower expression was found in cells of the inner nuclear layer of the retina, glomerular cell layer of the olfactory bulb, and medial aspect of the arcuate nucleus of the hypothalamus. The low levels of expression in the latter nuclei are consistent with the paucity of effects of cocaine in visual and olfactory systems, failure to detect photoaffinity-labelled transporter protein in hypothalamus or olfactory bulb, and observations that little or no damage is found in dopaminergic neurons outside the basal midbrain in idiopathic Parkinsonism. PMID- 8479288 TI - Different posttranscriptional controls for the human neurofilament light and heavy genes in transgenic mice. AB - To investigate the mechanisms regulating neurofilament gene expression, we generated transgenic mice with high copy number of the intact human neurofilament light (NF-L) and heavy (NF-H) genes. Overexpression in transgenic mice of NF-L mRNA from 3- to 5-fold in different regions of the central nervous system (CNS) resulted only in a mild increase of 10-50% in the levels of NF-L proteins. The failure to enhance NF-L protein content was not due to interspecies differences in posttranscriptional NF-L regulation. For instance, based on specific immunodetection, it is estimated that human NF-L proteins composed 80% of total NF-L content in the spinal cord of transgenics. In contrast to the situation with NF-L, the CNS of transgenic mice bearing multiple copies of the human NF-H gene showed comparable increases in the levels of NF-H mRNA and proteins. These results suggest that the NF-L and NF-H genes are subject to different posttranscriptional regulation in the CNS. In vivo labeling of newly synthesized proteins by injection of [35S]methionine in the spinal cords of normal and transgenic mice provided evidence that the posttranscriptional regulation of NF-L expression in the CNS must occur, at least in part, at the level of translation. PMID- 8479289 TI - Reduction of calbindin-28k mRNA levels in Alzheimer as compared to Huntington hippocampus. AB - Disturbances in calcium homeostasis have been observed to be associated with Alzheimer's and other neurodegenerative diseases. Increased total calcium levels and decreased levels of calcium binding proteins have been found in Alzheimer brain tissue. However, the mechanism behind these disturbances remain unknown. In situ hybridization with tritiated antisense RNA probes for the calcium binding proteins, calbindin-28k and calmodulin, was used to examine the expression of genes coding for these proteins in Alzheimer and Huntington brain tissues matched for age, agonal process and autopsy interval. mRNA levels for calbindin-28k were reduced by 35% in CA1 and CA2 regions of Alzheimer hippocampus, as compared to Huntington control. In contrast, calmodulin expression was unchanged in CA1 but reduced by 30% in CA2. mRNA expression of calbindin-28k and calmodulin in Alzheimer temporal cortex did not differ from control. There were no significant differences in calcium binding protein message levels in cerebellar Purkinje cells between Alzheimer and Huntington control. There was no correlation between calcium binding protein message levels and brain weight, autopsy interval, patient age or the extent of neurofibrillary degeneration. Instead, decreased calbindin-28k expression in Alzheimer-affected hippocampus was due to an increase in the percentage of neurons expressing lower message levels for these proteins. PMID- 8479290 TI - Regulation of growth-associated protein 43 (GAP-43) messenger RNA associated with plastic change in the adult rat barrel receptor complex. AB - Plastic change occurs in the adult rat barrel receptor complex following peripheral deafferentation by removal of facial vibrissae (vibrissectomy) and can be prevented by prior depletion of brain norepinephrine. Growth-associated protein (GAP-43, B50, F1, pp46), a marker for synaptic reorganization, increases in the barrel cortex of adult rats following both peripheral and central deafferentation. Here we followed changes in GAP-43 mRNA expression in the barrel receptor system following vibrissectomy. Adult rats had unilateral total vibrissectomy with sparing of the central (C3) vibrissa. By in situ hybridization, GAP-43 mRNA first increased at 24h (9%, P < 0.05) in the ipsilateral trigeminal complex. Levels remained elevated (up to 25% of the unlesioned side) over the next 6 days, decreased to 88% at 7 days and returned to control levels at 14 days. Contralateral barrel cortex levels of GAP-43 mRNA increased by 14% at 4-5 days remained elevated through 7 days and returned to control levels by 14 days. Increased GAP-43 mRNA levels 6 days after vibrissectomy were reproduced by complete transection of the infraorbital nerve and were blocked by depletion of brain norepinephrine. No change occurred in ventrobasal thalamus GAP-43 mRNA at any time. Dot blot and Northern blot hybridizations of GAP-43 mRNA after vibrissectomy showed a 43% increase in the ipsilateral trigeminal complex and a 16% increase in the contralateral barrel cortex at 3 days and an 84% increase in ipsilateral trigeminal and 50% increase in contralateral barrel cortex GAP-43 mRNA at 6 days, respectively. Thus, deafferentation-induced plasticity in the barrel pathway depends upon norepinephrine and is associated with increase in both GAP-43 mRNA and protein suggesting that this may involve a structural change. PMID- 8479291 TI - Multiple mRNA species of choline acetyltransferase from rat spinal cord. AB - A cDNA library directed by a specific primer was constructed from the rat spinal cord and screened with 32P-labeled rat choline acetyltransferase cDNA which was recently isolated in this laboratory. Sequence analysis of 29 clones indicated that there are four types of cDNA (R1-, R2-, N1- and M-types). The nucleotide sequences in these cDNAs were identical in the coding region and the first 38 bp of the 5'-noncoding region, but differed in the 5'-noncoding region upstream of 38 bp. The R1-type was identical to the cDNA previously cloned from the rat spinal cord. The M and N1-type cDNAs both had sequences homologous to that of the cDNA previously obtained from the mouse spinal cord. Polymerase chain reaction analysis confirmed the presence of these 4 types of mRNA and found another type (N2-type) of transcript. The numbers of cDNA clones isolated and the relative amounts of polymerase chain reaction products for each type of mRNA suggested that the most abundant transcript was M-type. Sequencing of the genomic clone containing the 5'-region of choline acetyltransferase mRNA revealed that these five types of mRNA species were transcribed from three different promoter regions and produced by differential splicing of the 5'-noncoding exons. PMID- 8479292 TI - The expression of tropomyosin genes in pure cultures of rat neurons, astrocytes and oligodendrocytes is highly cell-type specific and strongly regulated during development. AB - Transcripts from the alpha-, beta- and delta-tropomyosin genes were studied during development of pure cultures of rat neurons, astrocytes and oligodendrocytes. The three cell types contained five alpha-tropomyosin messengers, produced using both alternative promoters and splicing; one was specific for mature neurons. The beta-tropomyosin gene is expressed only in astrocytes and the delta-tropomyosin gene in all three cell types, especially in immature cells. Most of the tropomyosin isoforms are highly cell-specific. Their developmental regulation involves either differential expression of genes, in neurons and oligodendrocytes, and/or changes in alternative splicing, in astrocytes, delta-Tropomyosin (TM-4) may be important during the growth of neuronal and glial cell processes, while specialized isoforms such as the neuron specific alpha-tropomyosin TMBr-3 may be involved in the function or plasticity of the mature cells. PMID- 8479294 TI - Muscle fatigue. June 1979. PMID- 8479293 TI - The complete amino acid sequence for brain beta spectrin (beta fodrin): relationship to globin sequences. AB - The amino acid sequence of mouse brain beta spectrin (beta fodrin), deduced from the nucleotide sequence of complementary DNA clones, reveals that this non erythroid beta spectrin comprises 2363 residues, with a molecular weight of 274,449 Da. Brain beta spectrin contains three structural domains and we suggest the position of several functional domains including f-actin, synapsin I, ankyrin and spectrin self association sites. Analysis of deduced amino acid sequences indicated striking homology and similar structural characteristics of brain beta spectrin repeats beta 11 and beta 12 to globins. In vitro analysis has demonstrated that heme is capable of specific attachment to brain spectrin, suggesting possible new functions in electron transfer, oxygen binding, nitric oxide binding or heme scavenging. PMID- 8479295 TI - Introduction: exercise capacities and adaptations of people with chronic disabilities--current research, future directions, and widespread applicability. AB - This symposium addresses the unique physiological problems, current research, future needs, and widespread applicability for research involving people experiencing five major chronic disabilities within the United States: quadriplegia, paraplegia, mental retardation, multiple sclerosis, and poliomyelitis. Each author represents ACSM members who, by their distinguished research efforts, exemplify scientists who have demonstrated their dedication to the specific needs of these populations. The papers will give a brief description of the pathophysiology of the disability and the resultant effects upon the group's acute response to exercise and their physiological adaptations to exercise programs. Each paper will include reports on the state of current research and what benefits to that group could be expected if a major research breakthrough occurred. Additionally, the papers will indicate the major research questions currently confronting each population and a brief statement about the strategy needed to resolve these questions. If applicable, the authors will address how such a model (of the specific disability/disease) could be used to better understand the able-bodied response to exercise. The purpose of this symposium, therefore, was not only to better understand the effects of exercise on persons having chronic disabilities, but from a physiological point of view, to use what we know about the response of people with chronic disabilities to better understand the able-bodied response. PMID- 8479296 TI - Exercise capacity of individuals with paraplegia. AB - Spinal cord injury below the first thoracic vertebra defines the condition of paraplegia, with common medical sequelae including impaired motor function, bone and muscle atrophy, poor myocardial function, and a general decline of physical fitness. Recently, there has been renewed interest in the role of exercise for improving the physical fitness, health, and rehabilitation potential of individuals rendered wheelchair dependent following spinal cord injury. This brief review examines the pathophysiology of paraplegia, outlines useful strategies for cardiorespiratory fitness assessment, discusses the current levels of cardiorespiratory fitness in individuals with paraplegia, and highlights a few unique responses to acute exercise in this population. PMID- 8479297 TI - Exercise responses and quadriplegia. AB - The purpose of this paper is to review the exercise physiology literature on spinal cord injured individuals with quadriplegia performing voluntary arm exercise and/or electrically stimulated leg exercise. The effects of level of injury, active muscle mass, and sympathetic dysfunction on acute physiologic adjustments during exercise testing and chronic training adaptations are discussed. Several topics for future research are suggested, including methods to achieve higher aerobic/cardiovascular fitness, reduce secondary cardiovascular/pulmonary disabilities and related health care costs, and promote health, wellness, and an active lifestyle. PMID- 8479298 TI - Physical fitness and exercise training of individuals with mental retardation. AB - Recent social policies have focused on reentering persons with mental retardation (MR) into the work force and the mainstream of society. However, as individuals with MR age, their rate of institutionalization greatly outweighs that of the general population as well as children with MR. Health care organizations have expressed serious concern about the impact of an aging population with disabilities, particularly the cost associated with institutionalization. Considering that cardiovascular disorders are more common in population with than without MR, and that physical fitness has been directly related to work productivity among individuals with MR, physical fitness and exercise training have important implications for this population. Yet, available data suggest that individuals with MR have low levels of physical fitness, a higher incidence of obesity, and may respond differently to exercise training than persons without MR. This paper reviews current knowledge of physical fitness status, impact of exercise testing and training, and identifies differences between populations with and without MR, with special emphasis on trends associated with aging. This review is limited to three physical fitness components: obesity, cardiovascular fitness, and muscular strength and endurance, as these components have been shown to impact health and well-being, and are related to work performance of persons with MR. Suggestions for future research are also provided. PMID- 8479299 TI - Exercise and multiple sclerosis. AB - Multiple sclerosis (MS) is a neurological disease characterized by a variety of potentially debilitating symptoms. The manner in which the disease affects each individual is unique; however, many individuals with MS have a normal life expectancy and remain ambulatory throughout their lives. Very little research has focused on understanding how MS affects basic physiologic responses during exercise. Four general topics have been addressed: autonomic control of heart rate (HR) and arterial blood pressure (BP), cardiorespiratory fitness, skeletal muscle function, and symptom instability under thermal stress. Abnormalities in cardiovascular reflexes have been observed in some MS individuals during quiescent testing; however, HR and BP responses during exercise have not confirmed such findings. Deficits in cardio-respiratory fitness appear to be present in moderately impaired individuals, which are not always present in minimally impaired persons. Similarly, abnormalities in skeletal muscle function have been reported in some individuals with MS, while absent in others. Training appears to improve both cardiorespiratory fitness and skeletal muscle function. Findings appear to be indirectly influenced by the level of physical impairment of the experimental sample. This factor needs to be considered in sample selection, as well as in analyzing and reporting data. Elicitation of symptoms in response to thermal stressors has been documented by several investigators using unreliable techniques to measure core temperature. The use of more valid methods during rest and exercise have not confirmed the relationship between symptoms and core temperature changes. It may be that thermal sensitivity, although typically reported by most MS individuals, is a symptom that is very unique to each individual and sample selection may have indirectly contaminated results in past research. Considerations for future research are discussed. PMID- 8479300 TI - Poliomyelitis and the post-polio syndrome: exercise capacities and adaptation- current research, future directions, and widespread applicability. AB - Poliomyelitis is an acute viral disease that attacks the brain and the ventral horn of the spinal cord. Damage to the lower motor neurons usually results in atrophy and weakness of muscle groups, perhaps paralysis and possibly deformity. A second type, bulbar poliomyelitis, infects the medulla oblongata and may result in dysfunction of the swallowing mechanism along with respiratory and circulatory distress. Minor forms of poliomyelitis result in fever, sore throat, headache, and upper body stiffness, but leave no significant atrophy or paralysis. The purpose of this paper is to review post-polio syndrome (PPS) as well as the effect of exercise on the symptoms and morphologic adaptations to PPS and where future research efforts should be directed. The most common features of PPS for over 350,000 afflicted survivors include general fatigue, weakness, and joint/muscle pain. The primary reasons for these symptoms include 1) destruction of the anterior horn cells by the polio virus, leaving fewer motor neurons to induce muscle contraction; 2) unaffected motor unit enlargement by reinnervation through terminal sprouting; and 3) defective transmission at the neuromuscular junction secondary to failure of terminal axonal sprout. Acute responses to resistive exercise suggest significant muscle strength decrements in the knee extensors compared with similar aged people without polio. However, limited training investigation indicates significant strength increases for the knee extensors following at least 6 wk of training. Acute aerobic responses also differ significantly from those observed in aged-matched control subjects. Chronic aerobic responses to limited training studies suggest significant elevations in maximal oxygen uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479301 TI - Effects of Ca(2+)-channel drugs on K(+)-induced respiration in skeletal muscles. AB - When skeletal muscles are exposed to elevations in extracellular K+, they experience a significant and long-lasting increase in O2 uptake. The basis for this response is unknown but may be related to an influx in extracellular Ca2+ ions during sarcolemmal depolarization. The purpose of this study was to determine if altering Ca2+ entry, either by removal of Ca2+ from the bathing fluid or by exposing muscles to selective Ca(2+)-channel agonists or antagonists, would affect K(+)-induced respiration. Isolated frog sartorii muscles were incubated in normal Ringer's solution (R) or a modified Ringer's containing 10 or 18 mM KCl. O2 uptake increased 83.7% in R+10 mM KCl and 502.2% in R+18 mM KCl. Incubation in Ca(2+)-free R+18 mM KCl containing Ni2+ in place of Ca2+ depressed the metabolic response to elevated K+. O2 uptake increased 234.5% in R+18 mM KCl containing Ni2+ and 80.6% in R+18 mM KCl containing Mg2+. Similarly, addition of the Ca(2+)-channel antagonists (gallopamil (D600) and diltiazem (DILT)) to R+18 mM KCl also depressed the respiratory response to elevated K+. O2 uptake increased 224.2% and 133.1% in R+18 mM KCL containing D600 and DILT, respectively. Conversely, addition of the Ca(2+)-channel agonists (Bay K 8644 (BAY) or palmitoyl carnitine (PC)) to R+10 mM KCl enhanced the metabolic response to elevated K+. O2 uptake increased 278% and 438.9% in R+10 mM KCl containing BAY and PC, respectively. These results indicate that the stimulatory effects of elevated extracellular K+ on skeletal muscle respiration are at least partially dependent on the availability of extracellular Ca2+ and its subsequent entry during membrane depolarization. PMID- 8479302 TI - 31P-MRS of quadriceps reveals quantitative differences between sprinters and long distance runners. AB - Phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS) has been used to characterize the spectral pattern of quadriceps muscle at rest for sedentaries (N = 10), sprinters (N = 12), and long-distance runners (N = 10). Intracellular pH (pHi), phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE), adenosine triphosphate (ATP) and total phosphate (Pt), defined as the sum of the areas of PCr, PDE, Pi, and 3 times the beta-ATP resonances, were obtained from all spectra. The pHi and ATP/Pt ratio were the same in the three groups of people studied. The PCr/Pi and PCr/Pt ratios were significantly lower and the Pi/Pt ratio was significantly higher for long-distance runners than for sprinters and sedentaries, while the PDE/Pt ratio was significantly lower for sprinters than for sedentaries and long-distance runners. Furthermore, the PCr concentration for sprinters and sedentaries was significantly higher and the Pi was significantly lower than for long-distance runners. The results obtained in this study can be explained by the accepted differences in fiber type composition between sprint and endurance athletes. We suggest that 31P-MRS at rest could be used to monitor noninvasively the individual adaptive response to training in the metabolic characteristics of the athlete muscle fiber. PMID- 8479303 TI - Effect of continuous infusion of an anabolic steroid on murine skeletal muscle. AB - The purpose of this study was to investigate whether continuous infusion of an anabolic steroid, stanozolol, would alter skeletal muscle size and performance in sedentary male mice. The study was performed as a preliminary to an investigation on the effect of anabolic steroids on skeletal muscle regeneration in the mdx mouse, an animal model used for the study of Duchenne muscular dystrophy. Skeletal muscle structure and contractile behavior, and heart, liver, kidney, and testis wet weights were assessed after 3 or 6 wk of continuous exposure to one of two concentrations of stanozolol. Continuous release pellets containing either a high (1.5 mg) or low (0.5 mg) concentration of stanozolol were implanted into 8 wk-old C57BL/6J male mice. Control mice were implanted with pellets containing the drug vehicle. Stanozolol infusion had no significant effect on the contractile strength or mass of either fast-twitch extensor digitorum longus or slow-twitch soleus muscle. The resistance to fatigue of both muscles, assessed in vitro, was unaffected by stanozolol; however, postfatigue recovery of soleus twitch and tetanic tension after 3 wk of treatment was significantly (P < 0.05) increased in high-dose mice compared with control and low-dose mice. Androgen sensitive muscles, bulbocavernosus and levator ani, were significantly (P < 0.05) increased in wet weight after 3 wk of stanozolol treatment, but were not significantly different from control muscles after 6 wk, suggesting that continuous infusion produced a tolerance to the drug. Similarly, heart wet weight was significantly (P < 0.05) increased in stanozolol-treated mice compared with control after 3 wk, but not after 6 wk. Testis wet weight was significantly (P < 0.05) decreased in low-dose mice compared with control mice at 3 wk, but not at 6 wk. Plasma testosterone concentration was not significantly different between any of the groups after 3 or 6 wk of treatment. This study suggests that in the absence of other factors (e.g., high-intensity exercise or other degenerative changes in muscle fibers), continuous infusion of an anabolic steroid produces no significant effect on the growth, contractile strength, or endurance of hindlimb skeletal muscles. PMID- 8479304 TI - Is insulin-like growth factor gene expression modulated during cardiac hypertrophy? AB - The goal of this study was to examine the relationship between work-induced cardiac hypertrophy and insulin-like growth factor-I and -II (IGF-I and -II) mRNA expression in adult female Sprague-Dawley rats. Increased cardiac work was induced by coarctation, which involved placing a constricting silk ligature around the abdominal aorta to increase peripheral resistance. Cardiac hypertrophy was determined by measuring in vivo left ventricular protein synthesis rates. There was a rapid increase in left ventricular weight (LV) [both absolute and relative to body weight (mg tissue.100 g-1 body weight)] following the coarctation surgery. By the third day following coarctation, LV weight was increased approximately 20% and reached 24% by the 10th day as compared with controls. Protein synthesis rates increased dramatically, reached a peak level at 3 d (133%.d-1) compared with 29% Ks.d-1 in the sham operated group and then began to slowly decrease toward control rates. The fractional synthesis rates of total protein in the LV were unchanged 1 d post-surgery. IGF-I mRNA content in the LV decreased to approximately 38% below the control content at day 1. However, by 3 d post-surgery IGF-I mRNA content increased to 30-50% above controls, were 31% above control by day 7, and remained elevated thereafter. On the other hand, IGF II mRNA content remained constant throughout the 10 d post-surgery. Work necessitated increase in cardiac protein mass may be mediated, in part, by a local autocrine/paracrine production of IGF-I. PMID- 8479305 TI - Alterations in inspiratory and leg muscle force and recovery pattern after a marathon. AB - We measured lung mechanics and metabolic parameters, first in a series of 15 marathon (M) and 12 half-marathon (H) runners, before and 2.5 h after the race, in order to assess the running effect on respiratory muscles. Maximal static inspiratory (Pi) and expiratory (Pe) pressures, maximal voluntary ventilation (MVV), blood lactate (LAC), arterialized blood gases (ABG), plasma glucose (GLU), and, with a visual analog scale, subjective tiredness were assessed. Pi decreased in M and H without change in Pe, MVV, or lung mechanics; it was still abnormal 2.5 h after the race and did not correlate with LAC, ABG, training parameters, running times, or subjective tiredness. A second study of six other M compared Pi, Pe, adductor pollicis longus (Ppol), and triceps surae (Ptri) forces, aiming to: 1) assess the reproducibility of the prolonged Pi decrease without Pe change, 2) prove that such a decrease corresponded to a real reduction in inspiratory muscle force and was not due to a poor collaboration of the subjects, 3) correlate Pi decrease with the force loss of a potentially tired leg muscle: the triceps surae. We observed a significant and similar decrease in Pi and Ptri, but no change in Ppol and Pe. Moreover, the high correlation between Pi and Ptri diminutions suggested a similar recovery pattern for inspiratory and leg muscles. In conclusion, the prolonged decrease in Pi after such races is compatible with inspiratory muscle fatigue, which, as well as its recovery, is similar to leg muscle tiredness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479306 TI - Interrelationships between mechanical power, energy transfers, and walking and running economy. AB - The interrelationships between aerobic demand, kinematic and kinetic-based estimates of mechanical power output and energy transfer, and total body angular impulse (summation of net joint moments integrated with respect to time over a stride) were quantified for walking at 1.69 m.s-1 and running at 3.35 m.s-1 to assess the ability of these various biomechanical expressions to explain interin dividual differences in walking and running economy. Fourteen healthy men participated in the walking study and 16 recreational male runners were subjects for the running analysis. Each subject performed treadmill locomotion for determination of aerobic demand and overground locomotion from which biomechanical measures were quantified. It was expected that mechanical power and angular impulse expressions would correlate positively with aerobic demand while energy transfer expressions would correlate negatively. Correlations between aerobic demand and power estimates primarily were positive, but explained no more than 32% of the variability in walking or running VO2 (center of mass model: 0.22 < r < 0.57; segment-based model: -0.02 < r < 0.20; kinetic model: -0.07 < r < 0.22). Total body angular impulse also correlated positively with aerobic demand (0.32 < r < 0.42). Energy transfer expressions from the various analytical models showed no consistent relationship with aerobic demand, either in terms of magnitude or direction (-0.26 < r < 0.48). It was concluded that mechanical power, energy transfer, and angular impulse expressions frequently used in analyses of gait explain only a small proportion of normal interindividual variability in the aerobic demand at a given speed of walking or running. PMID- 8479307 TI - State anxiety and ambulatory blood pressure following resistance exercise in females. AB - The purpose of this investigation was to examine state anxiety and blood pressure responses during ambulatory recovery from resistance exercise. Fourteen females completed three separate bouts of resistance exercise in which the sets (N = 3), repetitions (N = 10), exercise type (knee extension, knee flexion, arm pull down, chest press, shoulder press, and abdominal curl), and time (30 min) were held constant, but the intensity was manipulated to equal 40%, 60%, and 80% of the 10 repetition maximum for each exercise. Immediately before as well as 1, 15, 30, 45, 60, 75, 90, 105, and 120 min following the cessation of exercise blood pressure and heart rate were assessed. State anxiety assessments were initiated immediately following blood pressure measurements. The subjects were ambulatory during the post-exercise period, and information about body posture during the cardiovascular assessments was obtained. MANOVAs, ANOVAs, and Tukey tests revealed that post-exercise state anxiety levels were reduced compared with pre exercise values from 90 to 120 min following exercise. Systolic blood pressure was elevated at 1 and 15 min following the 80% intensity condition, and at 1 min following the 60% intensity condition. It is concluded that during ambulatory recovery from resistance exercise: 1) reductions in state anxiety are realized; and 2) systolic blood pressure, in contrast to what has been shown to occur following aerobic exercise, is not reduced. PMID- 8479308 TI - Magnetic resonance imaging determination of left ventricular mass: junior Olympic weightlifters. AB - The relationship between left ventricular mass (LVM) and peak VO2 in junior elite Olympic-style weightlifters and sedentary subjects was investigated. Ten male weightlifters (mean +/- SE, age = 17.5 +/- 0.4 yr, wt = 72.9 +/- 3.3 kg) and 15 sedentary males (age = 18.8 +/- 0.4 yr, wt = 69.6 +/- 2.0 kg) served as subjects. Peak VO2 was measured using a continuous, incrementally loaded bicycle ergometry protocol. LVM was measured using magnetic resonance imaging techniques. Absolute peak VO2 was not significantly different (P > or = 0.05) between the weightlifters and the control subjects (3.5 +/- 0.1 vs 3.3 +/- 0.11.min-1). Absolute LVM (g) was significantly (P < or = 0.05) correlated to absolute peak VO2 (1.min-1) in the weightlifters (r = 0.723), but not in the control subjects. No other correlations between LVM in absolute or normalized by body weight, body surface area, or fat free mass terms, and absolute peak or normalized by body weight peak VO2 were significant. The weightlifters absolute LVM was significantly greater (P < or = 0.05) than that of the controls (208.1 +/- 10.0 vs 179.7 +/- 8.4 g). LVM normalized by body weight and body surface area but not by fat free mass, was significantly greater (P < or = 0.05) in the weightlifters than the control subjects. These data indicate that LVM in junior elite weightlifters is greater than that of control subjects and absolute LVM is related to absolute peak VO2 in weightlifters but not control subjects. PMID- 8479309 TI - Prediction of percent body fat in adult males using dual energy x-ray absorptiometry, skinfolds, and hydrostatic weighing. AB - The purpose of this study was to compare the prediction of percent body fat (%FAT) by dual energy x-ray absorptiometry (DXA), skinfolds (SF), and hydrostatic weighing (HW) in adult males. Subjects were 35 adult male Caucasians (mean +/- SD; age: 39.1 +/- 14.0 yr, height: 180.6 +/- 5.3 cm, weight: 81.0 +/- 11.1 kg). %FAT, determined by HW with residual volume determined via O2 dilution, served as the criterion. DXA %FAT was determined by the Norland XR-26 (XR-26) bone densitometer and by the SF equations of Jackson and Pollock (JP) (1978), and Lohman (LOH) (1981). Criterion referenced validation included analyzing mean (+/- SD) %FAT values using a one-way ANOVA for significance, comparison of mean differences (MD), correlations (r), standard error of estimates (SEE), and total errors (TE). Significant differences were found between means of each method. The r (0.91) and SEE (3.0 %FAT) for DXA compare favorably with the established SF methods of JP and LOH for predicting %FAT; however, DXA demonstrated the largest MD (3.9 %FAT) and TE (5.2 %FAT). Regression analysis yields HW = 0.79* DXA + 0.56. The results do not support earlier research that found no significant difference between HW and DXA %FAT in males. The study suggests the density of the fat-free body (DFFB) is not constant, and that the variation in bone mineral content affects the DFFB, which contributes to the differences between DXA and HW %FAT. We recommend further research to identify inconsistencies between manufacturers of DXA equipment in prediction of %FAT in males. PMID- 8479310 TI - Accuracy of RPE from graded exercise to establish exercise training intensity. PMID- 8479311 TI - Effect of pre-existing health conditions on the results of reconstructive microvascular surgery. AB - The effect of different pre-existing health conditions on the results of reconstructive microvascular surgery are reviewed. These conditions include: age, vital organ failure, diabetes, arterial and venous diseases, medications, smoking, wound healing disorders, epidermolysis bullosa, hematological diseases, multiple injury patients, pregnancy, and neuropsychiatric disease. PMID- 8479312 TI - Operative complications and the management of intraoperative flow failure. AB - Free flap flow failure can be either that of an artery and/or vein(s). One approach is to ascertain precisely which vessel(s) is compromised, then figure out whether the problem is on the patient's side or the flap side or at the anastomosis itself. A well perfused patient can minimize a patient-side problem. An anastomotic problem can be revised with or without adding a graft. There is potential to avoid further anastomotic problems with the use of some form of anticoagulant. Problems on the flap side, if limited, can be dealt with by resection or repair. Anticoagulants may be of value. Occasionally, another free flap is needed. PMID- 8479313 TI - Monitoring techniques for the detection of flow failure in the postoperative period. AB - Free tissue transfer is now a commonly used reconstructive tool. Vascular compromise is still a common complication and salvage rates of compromised flaps have been in the region of 50%. Numerous monitoring techniques have been tried but there is yet no single technique which has enjoyed universal acceptance. This paper reviews the available techniques and indicates where current trends are leading. PMID- 8479314 TI - Ischemia reperfusion injury: a review. AB - Ischemia reperfusion injury is reviewed in the context of the evolution of flap research over the past decade. A description of the clinical relevance of this field is presented and the possible etiologies are reviewed. The pathophysiology of this injury is then explored in some detail. Both skin and myocutaneous flaps, in a variety of animal models, are discussed. Research performed in vitro, as well as in other organ systems similarly affected by ischemia and reperfusion, is also examined. Particular attention is placed on the function of several newly described inflammatory mediators where it appears relevant to future research and treatment in the field of reconstructive microsurgery. PMID- 8479315 TI - Pharmacologic intervention in ischemia-induced reperfusion injury in the skeletal muscle. AB - This article provides a concise review on the potential causes of ischemia induced reperfusion (I/R) injury and pharmacologic intervention in the skeletal muscle. Special emphasis is placed on the recent observation of the acute ischemic preconditioning phenomenon for prevention of I/R injury in skeletal muscle. Finally, the mechanism of ischemic preconditioning and its clinical applications for augmentation of skeletal muscle tolerance to prolonged ischemic insult are discussed. PMID- 8479316 TI - The medical leech: an old treatment revisited. AB - The treatment modality of choice for venous insufficiency after free tissue transfer or replantation remains surgical repair. When this is not technically possible, the use of medical leeches is a useful adjunct to treatment. This paper reviews the history of the use of leeches in medicine, the anatomy and physiology of Hirudo medicinalis, the techniques of leech therapy, and the complications and contraindications. PMID- 8479317 TI - Complications in head and neck microsurgery. AB - Microvascular surgery plays a vital role in head and neck reconstruction. This paper deals with the complications arising from this form of surgery. They can be classified as general complications, anastomotic problems, and specific problems related to particular donor and recipient sites. PMID- 8479318 TI - Complications and unsatisfactory results in the microsurgical reconstruction of lower extremities. AB - Complications and unsatisfactory results in the microsurgical reconstruction of lower extremities were reviewed in a chronological sequence. Perioperative complications were grouped into the following categories: improper patient or donor tissue selection, unsatisfactory choice of recipient site vessels, inadequate exposure of recipient site vessels, improper "insetting" of the free tissue transfer, extralumenal obstruction, and miscellaneous adverse factors. Vascular changes in the limb as a result of free tissue transfer are discussed. Discussion of late postoperative problems includes the long-term results of soft tissue and skeletal reconstruction. PMID- 8479319 TI - Experimental microsurgical vein grafts: quantitative temporal analysis of progressive media fibroplasia. AB - The sequential histopathologic changes in microvenous grafts placed in a microarterial system were studied. In 48 Sprague Dawley rats, a 1 cm segment of epigastric vein was interposed into a defect created in the femoral artery. Grafts were explored at 1, 2, 4, and 12 weeks. After an initial smooth muscle hyperplasia, a progressive fibroplasia of the media was observed. Only small focal areas of intimal hyperplasia were seen. The width of the media was measured with an eyepiece micrometer. A statistically significant (P < 0.01) increase in width from 17 microns at 1 week to 462 microns at 12 weeks was noted. Although this process has been described before, this is the first quantitative assessment. PMID- 8479320 TI - Colon transplantation: a new microvascular technique. AB - This paper describes a new transplantation technique, using the colon instead of the small bowel for intestinal transplantation. With microsurgical techniques, allogeneic colon transplantation was carried out in rats in a heterotopic fashion. The vascular pedicle containing the aortic cuff and the portal vein was anastomosed to the aorta and the inferior vena cava of the host, respectively. The technique has proven reliable and reproducible, and our preliminary results suggest that the colon produces a milder rejection response than transplantation of the small bowel. PMID- 8479321 TI - En bloc kidney and whole pancreaticoduodenal transplantation with bladder drainage in the rat: microsurgical technique and outcome. AB - A microsurgical technique for en bloc kidney and whole pancreaticoduodenal transplantation with bladder drainage employing triple vascular anastomoses without the need for a vascular cuff is described. Nineteen combined isografts were performed using this technique in inbred male Lewis (RT1:I) rats with streptozotocin-induced diabetes. Six recipients died within 1 month from early complications (two from uremia, two from pancreatitis, one from bleeding, one from peritonitis); the other 13 survived more than 1 month after transplantation with both the pancreas and kidney grafts functioning. Four of the 13 rats died after 1 month (one from uremia secondary to an obstructed ureter, one from unexplained uremia, one from peritonitis after a biopsy, and one of unknown causes). The pancreas isografts of two animals were excised at 1 and 3 months to confirm dependence on the graft; both animals became hyperglycemic after graft pancreatectomy and had immediate declines of urine amylase activity to normal. One animal was sacrificed at 3 months to determine the insulin content of its native and transplanted pancreas; insulin was very low in the former and normal in the latter. The remaining rats survived with both grafts functioning for at least 6 months (normoglycemic, high urinary amylase levels, normal or near-normal plasma creatinine concentrations), before being sacrificed within the context of other experiments and for histological observations. Both the kidney and pancreas isografts were well preserved microscopically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479322 TI - Replantation of a multiple digit and circular palm amputation: a case report. AB - A case of successful replantation of multiple digits and circular palm amputation caused by an industrial punch force is reported. The two-level amputation was reconstructed by first replanting the severed fingers to the palmar segment and then connecting the palm segment to the hand stump. An arterial crisis was treated with urokinase, and postoperative functional recovery is described. PMID- 8479323 TI - Connective tissue disease and autoantibodies in the kindreds of 63 patients with systemic sclerosis. The United Kingdom Systemic Sclerosis Study Group. AB - Systemic sclerosis (SSc) tends to occur in a sporadic fashion and familial occurrence of the disease is unusual. Nevertheless, reports of related connective tissue diseases (CTD), autoantibodies, or both in family members together with associations of certain HLA class II phenotypes with SSc suggest that genetic factors might play a part in susceptibility to the disease. Because of the relative rarity of SSc only a small number of family pedigrees have been studied previously. This report represents the largest study to date, to our knowledge, of family members of patients with scleroderma, and provides the opportunity to investigate the relative importance of genetic and environmental factors operating in the disease. The family pedigrees of 63 patients with systemic sclerosis were examined with respect to clinical, serologic, and immunogenetic features. Multiple cases of SSc were seen only in 1 family, in which the disease affected a father and daughter. Disease expression in these 2 individuals was very similar both clinically and serologically; relatives with other connective tissue diseases were found in 9 families, and nonspecific features of CTD such as Raynaud phenomenon, and arthralgia or arthritis, occurred commonly, especially in female relatives. Antinuclear antibodies (ANA) were also detected more frequently in relatives than in controls. However, antibodies previously demonstrated to have a high degree of specificity for SSc were confined to patients with this disease. Probands had an increase in the frequency of HLA-DR3, DR5, and C4AQO. Patients with diffuse scleroderma had an increased frequency of HLA-DR3, while those with the limited form of the disease had an increased frequency of HLA DR5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479324 TI - Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. AB - In the present study we have analyzed the prevalence and characteristics of the most relevant clinical and immunologic features in 1,000 patients with SLE. Several differences in the expression of the disease have been observed in relation to the patients' age at onset, sex, and autoantibody serology. The childhood-onset patients more often had malar rashes (55% vs 39%) and nephropathy (28% vs 15%) as presenting manifestations. During the evolution of the disease, these patients had an increased prevalence only of malar rash (79% vs 56%) and a lower prevalence of rheumatoid factor (6% vs 19%). The older-onset patients (age 50 or older) less often showed malar rash (21% vs 42%), arthritis (52% vs 71%), and nephropathy (3% vs 17%) as the first symptom. During the evolution of their disease, these patients had a decreased prevalence of malar rash (33% vs 60%), photosensitivity (29% vs 47%), arthritis (73% vs 85%), nephropathy (22% vs 41%), thrombosis (4% vs 15%), and anti-La antibodies (6% vs 20%), but an increased prevalence of sicca syndrome (33% vs 15%). Males more often had serositis (28% vs 16%) as a first symptom, but they presented with a lower prevalence of arthritis (74% vs 85%) during the evolution of the disease. The presence of ANA, a high titer of anti-dsDNA, rheumatoid factor, anti-ENA, and antiphospholipid antibodies also distinguished additional homogeneous SLE subsets of clinical significance. PMID- 8479325 TI - Herpetic infection, with especial reference to involvement of the nervous system. 1929. PMID- 8479326 TI - The spectrum of non-Candida fungal infections following bone marrow transplantation. AB - We evaluated a consecutive series of patients who underwent bone marrow transplantation (BMT) at a single institution between 1974 and 1989 for the occurrence of a non-Candida fungal infection in the first 180 days after BMT. Of the 1186 patients, 129 (11%) patients developed a total of 138 significant non Candida fungal infections in this period. Eight patients had multiple distinct infections. The most common isolate was Aspergillus spp. (n = 97), followed by Fusarium (n = 10), and Alternaria (n = 6). The 4 clinical subtypes of infections were minor skin or soft-tissue infections (n = 7), infections of a single organ or site (n = 61), disseminated fungal infection (n = 58), and isolated fungemia (n = 12). The respiratory tract was involved in 95% of single organ or site infections, and 84% of disseminated infections. Outcome was poor, with only 18% of patients surviving. The cause of death was directly related to the non-Candida fungal infection in 66% of patients who died. Mortality rates were significantly higher in patients with either single-organ or site infections (41%) or disseminated infections (83%). The cause-specific mortality rate was greatest following infections with Aspergillus, Chrysosporium, Fusarium, Mucor, or Scopulariopsis, in which there was a high potential for invasive disease and disseminated infection. In contrast, the cause-specific mortality rate was lowest in infections which were either isolated fungemia or were localized and amenable to surgical debridement, most often seen with those infections caused by Acremonium, Alternaria, Penicillium, and Saccharomyces. The spectrum of clinical infections caused by these uncommon non-Candida fungal isolates both in our series and in the literature is reviewed. These unusual opportunistic fungal isolates are now gaining recognition in immunosuppressed patients such as the BMT population, and have a significant impact on patient outcome. Effective therapy of non-Candida fungal infections remains difficult. Early aggressive surgical debridement appears to be important in control of localized invasive infections. Prolonged therapy with amphotericin B is the standard of care, although the role of the newer antifungal agents is not yet well-defined. Ancillary roles may also be provided by granulocyte transfusions and the colony-stimulating factors. PMID- 8479327 TI - Infective endocarditis at a large community teaching hospital, 1980-1990. A review of 210 episodes. AB - We studied 210 episodes of infective endocarditis in 204 patients. The prevalence of this disease in our series ranged from 0.32 to 1.30 (mean, 0.75) episodes per 1000 admissions per year. There were 115 male and 89 female patients, whose ages ranged from newborn to 91 years (median, 60-70). One-hundred-and-forty-eight episodes involved host valves and another 33 episodes occurred in intravenous drug users. There were 2 episodes of early and 27 episodes of late prosthetic valve endocarditis. Staphylococcus aureus accounted for 99 episodes (47.1%), alpha-hemolytic streptococci for 29 episodes (13.8%), enterococci for 11 episodes (5.2%), culture-negative endocarditis for 11 episodes (5.2%), and other organisms for 60 episodes (28.6%). Severe back pain was the chief complaint in 15 patients. 2-D echocardiography was performed in 164 episodes, results in 67 (40.9%) of which were positive. Valve surgery was performed in 29 episodes (23 host valves and 6 prosthetic valves). The overall mortality was 21.4%. Autopsy was performed in 22 of the 45 patients who died (48.9%). The mortality rate increased with age, (10.1% and 31.5% for patients < 60 years old and 60 years or older, respectively (p < 0.001). PMID- 8479328 TI - Prevalence of obesity in adults with mental retardation: implications for health promotion and disease prevention. AB - The purpose of this study was to determine the incidence of obesity among 364 adults (mean age, 36.8 years) with mental retardation living in four residential settings. Skinfold measurements were used to measure adiposity. Results indicated that rates of obesity were significantly higher among females, subjects with severe mental retardation had the lowest overall rates of obesity, and the institutional group had the lowest incidence of obesity. These findings indicate a need for more investigation into the caloric intake and energy expenditure of adults with mental retardation, specifically focusing on level of retardation and living arrangement. PMID- 8479329 TI - Use of blacklight as visual stimulation for people with profound mental retardation and multiple handicaps. AB - Nineteen people with profound mental retardation and multiple handicaps who lived in a large ICF/MR facility were given visual stimulation in a blacklight environment. A comparison was made between conditions of blacklight and normal light for tracking and reaching. The students performed reliably higher under conditions of blacklight. In the blacklight environment, which removed distracting stimuli and exaggerated critical features, students were able to respond better to visual cues. PMID- 8479330 TI - Education of children with mental retardation in the Arab countries. AB - An overview of current issues in the education of children with mental retardation in Arab countries was presented and salient features of available programs were described. Major problems facing Arab practitioners working with this population were also discussed. The conclusion was made that despite serious challenges, special education programs for children with mental retardation in Arab countries are gradually evolving, making the outlook for these children more promising. PMID- 8479331 TI - On the importance of helping families: policy implications from a national study. AB - This study is a companion to our 4-year study (Birenbaum, Guyot, & Cohen, 1990) on financing health care for individuals with autism or severe mental retardation. We reported on nonmedical expenditures and opportunity costs pertaining to maintaining a child or young adult with serious developmental disabilities in the home or in residential care and discussed policy implications for assisting their families. We proposed that (a) personal care and family support should be included in health care requirements, (b) family-centered care should be promoted, (c) appropriate programs and care should be provided for young adults no longer in school, (d) financing and organizing of family supports and subsidies should be administratively simple, (e) Medicaid should be expanded to increase use of home- and community-based services, and (f) financial support should be provided to families. PMID- 8479332 TI - Comparison of families of children with mental retardation and families of children without mental retardation. PMID- 8479333 TI - On the medicalization of family caregiving. PMID- 8479334 TI - In the best interests of the family: some comments on Birenbaum and Cohen's recommendations. PMID- 8479335 TI - Injuries in young people with developmental disabilities: comparative investigation from the 1988 National Health Interview Survey. AB - Injury rates among community-based young people with developmental disabilities were compared to controls and to young people with chronic illness and their controls, using data from the 1988 National Health Interview Study. Children with disabilities had higher injury rates than did controls, but children with chronic illness did not. Preschoolers with chronic illness tended to have lower rates of injury. Analyses were also conducted by sex. These injury patterns may be due to both impaired function resulting from disability and overprotection with decreased exposure to risk. PMID- 8479336 TI - The era of optimism, 1850-1870: a preliminary reappraisal. AB - Hervey B. Wilbur founded the Barre School, the first private residential school in the United States, in 1848. Samuel G. Howe began the Massachusetts School for Idiotic and Feeble Minded Youth, the first residential public school in the United States, in 1850. Correspondence of the period indicates educational results were less than expected and that strains of pessimism surfaced quite early. By the late 1850s, both Howe and Wilbur raised the possibility of custodial care. The primary source material suggests that the disillusionment with the residential facility as a vehicle for reform and habilitation reflected the decreased faith in moral education and remediation of problems associated with insanity, criminal behavior, and the poverty in the pre-Civil War period. PMID- 8479337 TI - Behavioral problems and medication utilization. AB - Although psychotropic medications are commonly used with older adults who have mental retardation, patterns of medication use for this group are not easily determined. Our objective was to explore relations between prescribed psychoactive treatments and rated behavioral difficulties. Adults with moderate mental retardation living in congregate and group care settings were rated by care providers using a standard behavior rating instrument. Older adults demonstrated a tendency toward higher medication utilization. Results indicated higher drug utilization in the larger setting despite the fact that behavior problems and cognitive level was matched across all settings. Medication utilization appears to be related to multiple factors, not only the behavioral or cognitive characteristics of adults with mental retardation. PMID- 8479338 TI - Percolation phenomenon: the effect of capillary network rarefaction. AB - The relationship between microvascular network resistance and functional capillary density was investigated by computer simulation. A model of spinotrapezius muscle microcirculatory network was constructed from measured data of vessel length and diameter. Progressive rarefaction was simulated by random stepwise removal of capillaries from the network. The flow distribution in the network was calculated after each step of capillary removal. Network resistance increased little when decreases in functional capillary density were less than 30%. Furthermore, capillary flow did not decrease and its variance across the network was unchanged despite the gradual flow redistribution. However, with further decreases in capillary density, network resistance increased in a double exponential fashion. The resistance approached infinity at a critical value of functional capillary density termed the percolation threshold. The value of this parameter varied between 56 and 62% and it was lower when capillaries with the lowest flow were preferentially removed. PMID- 8479339 TI - Comparative evaluation of laser Doppler flux metering, bulbar conjunctival angioscopy, and nail fold capillaroscopy in sickle cell disease. AB - Eleven adult patients with stable sickle cell disease (SCD) were investigated twice at a 15-day interval by nail fold capillaroscopy (NFC), bulbar conjunctival angioscopy (BCA), and laser Doppler flux metering (LDF). NFC and BCA are essentially descriptive. NFC revealed, in some patients, network patterns similar to those observed in vasculitis. BCA provides a reproducible method for the visual assessment of the microcirculation. When using a rating scale with five criteria it identified abnormalities related to both altered red blood cells and vascular morphology but failed to discriminate between patients. LDF, in contrast, is quantifiable and showed reproducible characteristic reactive alterations of vasomotion in response to ischemia after 3 min of occlusion. The SCD patients had a delayed response, best measured by the recovery half time, which was four to five times longer than that of normal subjects. In addition, the cold provocative test was always abnormal, as evidenced by a significant drop in the contralateral flux, and was often poorly tolerated. The observed trends suggest that BCA and LDF should be performed in a large cohort of patients, both in the steady state and during vasoocclusive crises. These methods seem to be useful complementary noninvasive procedures to cellular and clinical evaluation monitoring for therapeutic trials. PMID- 8479340 TI - A simplified method for culture of endothelial cells and analysis of adhesion of blood cells under conditions of flow. AB - We have developed a simplified technique for culturing human umbilical vein endothelial cells under shear flow conditions, using prefabricated glass microcapillary tubes ("microslides") with a well-defined rectangular cross section and good optical quality. These microslides have been incorporated into a controlled flow system for quantitative video-microscopic analysis of the adhesion of blood cells to endothelial cells. Microslides were pretreated with 3 aminopropyltriethoxy-silane, or gelatin, and then loaded with a suspension of endothelial cells. After the cells had settled and attached to the substrate, the microslides were inserted into a flow-based culture system. Medium was drawn through them at intervals or continuously until confluency was reached (approximately 24 hr). Cells were cultured at wall shear stresses over a range 0.06 to 2.2 Pa. For adhesion assays, the endothelialized microslides were attached to microscope slides, and suspensions of blood cells were drawn through at desired wall shear stresses (0.02-0.5 Pa). Adhesion of malarial-infected red blood cells and of neutrophilic granulocytes was quantitated by direct microscopic observation. The adhesive behavior of both cell types closely resembled that previously described by ourselves and others using flow chambers incorporating endothelial-coated glass coverslips. The use of microslides represents a significant simplification of methodology for endothelial cell growth and adhesion studies under flow conditions. PMID- 8479341 TI - Quantitative analysis of the Landis method. AB - Landis developed the single capillary micro-occlusion method for the determination of the capillary filtration coefficient, Lp. More recently, several modified versions of Landis's original procedure have been introduced in an attempt to measure Lp with greater ease and accuracy. Each of the techniques assumes that the capillary is a uniformly cylindrical indistensible tube. Since recently obtained experimental data have demonstrated that the capillary is compliant, a distributed mathematical model of the capillary was developed to reveal the extent to which capillary distensibility influences the measurement of Lp at different sites along the capillary. After assigning physiologic values to this modeled capillary, including Lp and the capillary wall's modulus of elasticity, Landis's method and two of its modified versions were performed on the modeled capillary, with each yielding values for Lp at 10 different locations along the capillary. Comparison of these 10 computed Lp values with the corresponding Lp values defined in the modeled capillary demonstrates that capillary distensibility can introduce significant error into the measurement of Lp. PMID- 8479342 TI - Reproducibility of the finger cooling test. AB - A finger cooling test is used to objectify Raynaud's phenomenon and to assess its severity. For this purpose, finger skin temperature (FST) and laser Doppler flux (LDF) are measured on the fingertips before and during cooling of the hand (16 degrees water bath for 5 min) and a subsequent recovery period (20 min). To study reproducibility, this test was performed twice within 3 months in 34 healthy subjects and in 56 Raynaud patients. Three test parameters were used in the analysis: the baseline value, the value after 12 min of recovery, and the mean level during recovery. We determined the limits of agreement (mean differences between the first and the second test +/- 2SD) and the coefficients of variation. No systematic differences between the first and the second test were found. Outside temperature did not influence FST or LDF. FST was shown to have a better reproducibility than LDF. For the baseline value in the total group the coefficient of variation was 3.3% for FST and, rather high, 21.6% for LDF. The limits of agreement for the baseline value in the total group were -4.8 to 4.2 degrees for FST and -25.2 to 22.2 arbitrary units for LDF. In conclusion, the applied cooling test has limited value in individual cases, but can be useful when comparing large groups in pathophysiologic or therapeutic studies. PMID- 8479343 TI - Influence of selenium on the microvasculature of the retina. AB - The impact of small differences in selenium exposure during the first year of life was investigated in male Wistar rats. Forty-five rats were evaluated in two experiments. Rats were provided diets that contained sucrose as the sole carbohydrate to induce an elevation in blood triglycerides, cholesterol, glucose, and insulin. In each experiment one-half the rats received 0.1 mg Se/kg and the other half 0.2 mg Se/kg diet. Both levels of selenium supported normal activity of the marker for selenium sufficiency erythrocyte glutathione peroxidase. In experiment 1 rats were maintained in galvanized cages and in experiment 2 they were housed in stainless steel cages. In both experiments rats provided 0.2 mg Se/kg diet had fewer acellular degenerating capillaries and a higher ratio of pericyte to endothelial cells in the capillary wall than those fed 0.1 mg/kg as well as fewer vessels over the optic disc head. In the second experiment, the height of the central choroid was also greater in rats exposed to the higher level of selenium suggesting that the element protected the capillaries in this region from degeneration. In contrast to vascular tissue, the retinal parenchymal tissue was unaffected by the level of selenium exposure. These results are consistent with the hypothesis that the microvasculature has a unique requirement for selenium. PMID- 8479344 TI - Enhanced arteriolar vasomotion in rats with chronic salt-induced hypertension. AB - The aims of this study were (1) to determine if the establishment of hypertension in the Dahl salt-sensitive (DS) rat is accompanied by alterations in arteriolar vasomotion and (2) to explore the influence of endogenous nitric oxide on vasomotion in normotensive and hypertensive DS rats. Rhythmic diameter changes of arcading arterioles were studied in the superfused spinotrapezius muscle of DS fed high (4%) or low (0.45%) salt diets for 6 weeks. Mean arterial pressure for DS on high salt (166 +/- 7 mm Hg) was significantly greater than that for DS on low salt (131 +/- 9 mm Hg). There was no difference between hypertensive and normotensive DS in time-averaged arteriolar diameter, vasomotion frequency, or vasomotion cycle length. However, average vasomotion amplitude was 93% greater in hypertensive DS than in normotensive DS. Inhibition of nitric oxide synthesis with NG-Nitro-L-arginine methyl ester did not alter vasomotion in hypertensive DS, but increased vasomotion amplitude in normotensive DS to a level not different from that in hypertensive DS. L-Arginine had no effect on vasomotion in either group. Therefore, cyclic variations in arcade arteriole diameter are normally limited by basal nitric oxide, and the enhancement of these variations in animals with salt-induced hypertension may be attributable to the loss of this nitric oxide influence. The increased vasomotion amplitude and unchanged average diameter in hypertensive DS suggests a reduced hydraulic resistance within this particular segment of the arteriolar network. PMID- 8479345 TI - A computer controlled system for multiple site microcirculatory measurements. AB - A system has been developed for intravital microscopy studies that records optical signals at different tissue sites together with X-Y coordinates within an area of up to 100 cm2. Z axis coordinates can also be recorded. The system utilizes a computer and a motor-driven microscope stage to rapidly and repetitively move between selected sites. The system can also be used to map topological features and geometry. The application of the system to study spatial heterogeneity of changes in tissue metabolism with time and to map vascular network architecture is described. PMID- 8479346 TI - Preventing childhood allergy. PMID- 8479348 TI - Who are the elderly? PMID- 8479347 TI - Arthritis: the hidden disability. PMID- 8479349 TI - Effectiveness of low-dose intradermal hepatitis B vaccination. Five years' experience of primary vaccination. AB - OBJECTIVE: To determine whether intradermal hepatitis B vaccination is an effective procedure. DESIGN: A study of antibody responses to hepatitis B vaccine in 753 medical students. SETTING: Routine vaccination of medical students with intradermal doses of hepatitis B vaccines of various origins. OUTCOME MEASURES: Rates of seroconversion and geometric mean levels of antibody achieved. RESULTS: Seroconversion rates, indicated by antibody to hepatitis B surface antigen (anti HBs) levels of 10 mIU/mL or more, varied between 82% and 94.7% with different preparations of the vaccine. With a four-dose intradermal schedule over two successive cohorts, Engerix-B (SmithKline Beecham) gave better responses, in this context, than H-B-Vax II (Merck Sharp & Dohme). Any reactions to the vaccination were mild and local. CONCLUSION: The intradermal route is a practical method of vaccination against hepatitis B in healthy young adults when the cost of the vaccine is an inhibiting factor. PMID- 8479351 TI - Rubella vaccination and congenital rubella syndrome in Western Australia. AB - OBJECTIVE: To review the incidence of congenital rubella syndrome (CRS) and the acceptance of schoolgirl rubella vaccination in Western Australia (WA), and to determine whether any groups in the community are at increased risk of having a child affected by CRS. DESIGN: Review of records of the WA Birth Defects Registry for cases of CRS; survey of obstetricians for terminations of pregnancy for maternal rubella infection; survey of schoolgirls eligible for the 1991 annual rubella vaccination campaign; review of Perth Immunisation Clinic and rural community and child health records; review of the rubella immune status of women tested antenatally. MAIN OUTCOME MEASURES: The incidence rate of CRS per 10,000 live births in WA 1980-1990; the incidence of rubella-associated terminations of pregnancy during 1990 and 1991; trends in rubella vaccine acceptance among WA schoolgirls between 1971 and 1991; and the proportion of women attending antenatal clinics who showed satisfactory immunity against rubella, stratified by country of birth. RESULTS: The incidence rate of CRS in WA remains below 2 cases per 10,000 live births. Approximately 86% of Perth schoolgirls have been vaccinated against rubella. Rubella vaccine acceptance fell in some country areas during the late 1980s, but is now returning to acceptable levels. Women born in Asia are at greater risk of having a baby affected by CRS than women born in Australia. Babies with CRS may be born to women who have previously been vaccinated against rubella. CONCLUSIONS: The incidence of CRS has fallen dramatically since the introduction of the schoolgirl vaccination program, but there is still a need for mechanisms to identify and vaccinate non-immune women. PMID- 8479350 TI - Booster doses of hepatitis B vaccine: responses to low-dose inoculations. AB - OBJECTIVE: To examine the anamnestic response to hepatitis B vaccine in previously vaccinated subjects. DESIGN: Subjects who had received a course of hepatitis B vaccine at least two years previously had a sample of blood taken before and seven days after a low-dose booster of hepatitis B vaccine. SETTING AND PARTICIPANTS: A pilot group of laboratory scientists in the Microbiological Diagnostic Unit; fifth year medical students, University of Melbourne; and a group of ambulance officers from the Geelong Ambulance Depot (Victoria). All participants volunteered after having been informed of the study. OUTCOME MEASURES: Serum levels of antibody to hepatitis B surface antigen (HBsAg) were measured before and after the booster dose of vaccine and, when available, in serum taken a month after the end of the primary course of vaccine, and the changes in antibody level were studied. RESULTS: Although some individuals with a restricted antibody response were identified, most showed a quick response. There was limited evidence that this rise peaked early and began to fall within weeks. CONCLUSIONS: In many subjects, levels of antibody to HBsAg peak early after booster doses of vaccine but the rapid anamnestic response to small amounts of antigen make it probable that effective protection from symptomatic illness may be long lasting, when there has been a satisfactory primary response. This provides an argument for testing for adequate seroconversion after vaccination. PMID- 8479352 TI - The disabled elderly living in the community: care received from family and formal services. AB - OBJECTIVES: Based on a community sample, to assess the reasons disabled elderly people need care, the type of formal services they receive, the characteristics of their carers and the degree of psychological morbidity in these carers. DESIGN AND SETTING: A community survey of people aged 70 or more years living in Canberra or Queanbeyan. Survey participants were asked to nominate informants, who were interviewed about the subjects' state of health. The informants provided information on need for care, services received and the role of carers. Informants also reported on their own health, including symptoms of anxiety and depression. RESULTS: Elderly people needed care because of physical disability more often than behavioural disability. Those with physical disability received more formal services and more help from health professionals than those with behavioural disability. Contact with general practitioners was high for both disabled and non-disabled subjects. Carers of the physically disabled had raised levels of anxiety and symptoms of depression, and poorer self-rated health, but carers of the behaviourally disabled did not. Wives, daughters and husbands made up the biggest categories of carers and around two-thirds of carers were women. CONCLUSION: Family carers play an important role in maintaining disabled elderly people in the community and this role is often stressful. Formal services have to be aimed as much at the needs of the carers as at the disabled people themselves. PMID- 8479353 TI - Relevance of pharmacokinetics and pharmacodynamics. AB - Appropriate and rational use of drugs in the elderly is a matter of growing medical and social concern. The elderly as a group are particularly prone to adverse drug reactions. Such reactions have often been due to inappropriate drug prescribing, based on incomplete recognition and knowledge of changes in drug handling with age and pathological states associated with ageing. Recognition of such changes with modification of prescribing practice may lead to benefits by minimising the incidence of adverse drug reactions. This article discusses the current knowledge of age-related changes in drug absorption, distribution, clearance and sensitivity and some implications of these changes for clinical therapeutics in the elderly. PMID- 8479354 TI - Domestic violence and the general practitioner. AB - Domestic violence is a common social problem that raises many difficult questions and management issues for both the patient and the doctor. Domestic violence is an abuse of power within the relationship. Physical assault is common and serious, but psychological abuse is more damaging. Perpetrators of domestic violence do not usually perceive that they have a problem and no change in their behaviour is possible unless they want to change. For general practitioners the first step in dealing with domestic violence is detection, and that means acknowledging that it can exist in any patient. General practitioners have three choices in their management of victims of domestic violence: they can do nothing, they can be sympathetic only or they can be an agent of change. Effective management of domestic violence involves raising the victim's self-esteem so that she is able to alter her situation herself. PMID- 8479355 TI - Central nervous system tuberculosis in Australia: a report of 22 cases. AB - OBJECTIVE: To review the clinical features, treatment and outcome of patients with central nervous system (CNS) tuberculosis. DESIGN AND SETTING: A retrospective analysis of the case records of patients diagnosed as having CNS tuberculosis in a large Australian teaching hospital. PATIENTS: Twenty-two patients with CNS tuberculosis were identified between 1978 and 1989. Six patients (age range, 17-78 years) were Australian-born whites, seven patients (age range, 21-68 years) were overseas settlers in Australia and nine patients (age range, 14-56 years) were New Caledonians. The diagnoses included tuberculous meningitis, intracranial tuberculomas and intracranial tuberculous abscesses. These were confirmed by microbiology and/or histopathology in 16 patients and were presumptive in the remaining six. RESULTS: All patients were treated with antituberculous drugs and 14 received corticosteroids as well. Fourteen patients made a full recovery and two had mild residual neurological disability. Four patients died and two were left with severe residual disability. The neurological state of seven patients (all non-whites) deteriorated paradoxically after they started taking the antituberculous drugs. CONCLUSIONS: The diagnosis of CNS tuberculosis may be difficult to make, so therapy based on a presumptive diagnosis will often be needed because of the poor outcome if treatment is delayed. Computed tomographic scanning helps the initial diagnosis and demonstrates the processes underlying paradoxical deterioration, which may occur in the face of adequate antituberculous treatment. Corticosteroids are effective in treating this uncommon complication. PMID- 8479357 TI - Planning bedside teaching--3. Briefing before seeing the patient. PMID- 8479356 TI - Psychotropics, thiazide diuretics and hip fractures in the elderly. AB - OBJECTIVE: To determine whether psychotropic medications increase, and thiazide diuretics decrease, the risk of hip fractures in elderly Australians. DESIGN: Population-based case-control study. SUBJECTS AND SETTING: The population aged 65 years and over living in a defined area in western Sydney, Australia, during 1990 1991. Cases (n = 209) were recruited from hospitals and controls (n = 207) were selected by an area probability sampling method, with additional sampling from nursing homes. Response rates were 96% for cases and 84% for controls. MEASURES: Data were collected directly from subjects by questionnaire; a proxy respondent was required for 27% of subjects. In addition to medication use, information was also collected on potential confounders: alcohol consumption, body mass index, cognitive status, dairy product consumption, health status, physical activity, smoking history and type of residence. RESULTS: The use of temazepam, a short acting benzodiazepine, was associated with an increase in the risk of hip fracture--odds ratio, adjusted for age, gender and residence is 3.78; 95% confidence interval (CI), 1.60-8.92. After adjusting for multiple potential confounders by logistic regression, the odds ratio for temazepam use was 3.52. There was a non-significant (P > 0.05) increase in hip fracture risk associated with the use of antidepressants and antipsychotics. Thiazide diuretics were not associated with a risk of hip fracture--the multivariate-adjusted odds ratio was 0.98 (95% CI, 0.49-1.99). CONCLUSIONS: Temazepam may increase the risk of hip fracture in elderly people. The effect of thiazide diuretics on fracture risk should be assessed in a large randomised trial. PMID- 8479359 TI - The clinician and therapeutic drug monitoring in the 1990s. PMID- 8479358 TI - Screening for carriers of genetic disease: points to consider. PMID- 8479360 TI - Quality of life in cancer care. PMID- 8479361 TI - Head injuries from road accidents--a diminishing problem? PMID- 8479362 TI - Algal toxins and bellyaches beyond the Barcoo. PMID- 8479363 TI - Rubella vaccination. PMID- 8479364 TI - The effectiveness of rubella vaccine. PMID- 8479365 TI - Electrocution. PMID- 8479366 TI - Scombroid poisoning. PMID- 8479367 TI - Atrial fibrillation. PMID- 8479368 TI - Hormone replacement therapy and breast cancer. PMID- 8479369 TI - Hysterectomy. PMID- 8479370 TI - The cost of cost-of-illness studies. PMID- 8479371 TI - Ovarian carcinoma: a continuing challenge. PMID- 8479372 TI - Problems assessing aboriginal infant mortality. PMID- 8479373 TI - The potential for elderly donors to increase renal transplantation rates in Australia. AB - OBJECTIVE: To estimate the potential increase in renal donation rates if elderly donors (those over 60 years of age) were considered. DESIGN: Patients dying from acute brain damage resulting from stroke were identified using the Royal Melbourne Hospital (RMH) Stroke Service Register. Their records were retrospectively analysed to assess their eligibility as potential renal donors. SETTING: One hundred and ninety-eight patients dying from acute brain damage caused by stroke at a large metropolitan teaching hospital (RMH), from May 1987 to December 1990 inclusive. PATIENT ASSESSMENT: Patients were considered "eligible", "ineligible" or "possibly eligible" (requiring further assessment) as donors according to existing strict criteria (see methods) but irrespective of age. RESULTS: Of 198 stroke patients dying of brain damage, 92 satisfied the criteria of eligibility for renal donation; 51 of these were over 60 years old, yet only one became a renal donor. CONCLUSION: There is good evidence that elderly donors are acceptable for renal transplantation, yet they are not being referred. The consideration of elderly stroke victims as renal donors could have a dramatic effect on decreasing transplant waiting lists, increasing recipient patient well-being, and reducing hospital costs. PMID- 8479374 TI - Cholestatic hepatitis associated with flucloxacillin. AB - OBJECTIVE: To estimate the frequency of cholestatic hepatitis of uncertain origin occurring among persons who had recently received flucloxacillin, a drug which has recently been reported as causing cholestatic hepatitis, and to compare this frequency with that related to oxytetracycline, a drug which has seldom been reported as causing this disorder. DESIGN: A retrospective cohort study using data automatically recorded on general practitioners' office computers. SETTING: Some 600 general practices in the United Kingdom. SUBJECTS: 132,087 people who received flucloxacillin and 145,844 people who received oxytetracycline. MAIN OUTCOME MEASURE: Clinically documented cholestatic hepatitis of uncertain origin diagnosed 1-45 days after a prescription for flucloxacillin, 46-90 days after a prescription for flucloxacillin and, for comparison, 1-45 days after a prescription for oxytetracycline. RESULTS: There were 10 cases of cholestatic hepatitis of uncertain origin diagnosed within 45 days of receiving flucloxacillin that were either characteristic of or consistent with a syndrome recently described as being associated with this drug; there was one such case 46 90 days after a prescription for flucloxacillin; there were three such cases 1-45 days after a prescription for oxytetracycline. CONCLUSION: Flucloxacillin is a likely cause of cholestatic hepatitis. The risk is estimated to be in the range of 7.6 per 100,000 users (95% confidence interval, 3.6-13.9). PMID- 8479375 TI - Erythromycin-associated cholestatic hepatitis. AB - OBJECTIVE: To estimate the risk of cholestatic hepatitis of uncertain origin in patients who had recently received erythromycin, a drug which is known to cause this disorder. DESIGN: A retrospective cohort study using data automatically recorded on general practitioners' office computers. SETTING: Some 600 general practices in the United Kingdom. SUBJECTS: 366,064 people who received erythromycin. MAIN OUTCOME MEASURE: Clinically documented cholestatic hepatitis of uncertain origin diagnosed 1-45 days after a prescription for erythromycin. RESULTS: There were 13 cases of cholestatic hepatitis of uncertain origin diagnosed within 45 days of receiving erythromycin which were either characteristic of or consistent with a syndrome previously described as being associated with this drug. CONCLUSION: The risk of cholestatic jaundice associated with erythromycin is estimated to be in the range of 3.6 per 100,000 users (95% confidence interval, 1.9-6.1). PMID- 8479376 TI - Serological evidence of the three chlamydial species in an aboriginal community in the Northern Territory. AB - OBJECTIVE: To determine the pattern of seropositivity to the three species of Chlamydia in women and children from a single community. DESIGN: Testing of blood samples obtained during a prospective study of mothers and infants. For each individual, the sample giving the highest titre of antichlamydial antibody was included in the analysis. SETTING: The only health centre for a small rural community in the Top End of the Northern Territory. This served all 1200 or so residents, almost 95% of whom were Aboriginal. PARTICIPANTS: Sixty-one pregnant Aboriginal women at routine antenatal clinic visits, and 114 of their children aged between one and six years at the time of sampling. MAIN OUTCOME MEASURE: Specific IgG or IgM antibody to any of the three species of Chlamydia at titres > or = 32, as determined by micro-immunofluorescence. RESULTS: IgG antibody to one or more chlamydial species was found in 83.6% of mothers and 42.1% of their children. IgM antibody was found in five mothers and four children, in each case against only one chlamydial species. IgG antibody to C. trachomatis was found in 55.7% of mothers and 28.9% of children, to C. pneumoniae in 59.0% of mothers and 19.3% of children, and to C. psittaci in 29.5% of mothers and 17.5% of children. Log linear modelling gave positive correlations between seropositivity for C. trachomatis and C. pneumoniae (chi 2 = 9, P < 0.01), and for C. trachomatis and C. psittaci (chi 2 = 15, P < 0.001). Cross-reactivity was more evident in children than in mothers. CONCLUSIONS: This is the first Australian report providing serological evidence of exposure to the three chlamydial species in one community. The seropositivity patterns suggest complex interactions when all species are present. PMID- 8479377 TI - Admission rates for hip fracture in Australia in the last decade. The New South Wales scene in a world perspective. AB - OBJECTIVES: To study the changes in admission rates for hip fracture in New South Wales in the last decade; and to compare the age-adjusted rates with those from Europe, America and Asia. METHODS: Hospital discharge data for the years 1981, 1986 and 1989-1990 for New South Wales were used. The number of patients discharged with hip fracture (International Classification of Diseases code 820) as one of the diagnoses was calculated. Age-specific rates were calculated using the census population for 1981, 1986 and 1991. These rates were then directly standardised to the 1985 United States population and then presented with similarly adjusted rates from countries in Europe, America and Asia. RESULTS: For New South Wales men, the incidence rates of hip fracture (directly standardised to the 1985 United States population) for 1981, 1986 and 1989-1990 were 148 per 100,000, 181 per 100,000 and 182 per 100,000 respectively. In women, the rates for these three years were 437 per 100,000, 537 per 100,000 and 500 per 100,000 respectively. The age-adjusted rates for both men and women were high and were comparable to the rates in the United States and New Zealand. CONCLUSIONS: The incidence of hip fracture in NSW in the last decade was very high by world standards. The prevention of hip fracture is essential as the Australian population ages. PMID- 8479378 TI - Planning bedside teaching--6. Reflection on the clinical experience. PMID- 8479379 TI - Medicine in tropical Australia. AB - In the unique environment of Australia's tropical north there are endemic diseases inherited from Gondwana, others introduced from the north and from Europe, and a wide range of particularly venomous animals. There is continuing disparity in morbidity and mortality between Aboriginal people and other Australians in tropical areas and elsewhere. This is being addressed by the National Aboriginal Health Strategy, which emphasises social, environmental and economic issues, as well as control and coordination of services by Aboriginal and Torres Strait Islander communities. While the re-introduction of malaria remains a potential threat, together with other infections, current diseases in tropical Australia are being better elucidated; melioidosis is now recognised as the commonest cause of fatal [corrected] community-acquired pneumonia in the Top End of the Northern Territory, and a new focus of scrub typhus has been found. Sexually transmitted diseases are an urgent issue, especially for Aboriginal communities, given the potential impact of the human immunodeficiency virus. PMID- 8479380 TI - Molecular biology in ocular disorders. PMID- 8479381 TI - Qualitative research in medical practice. PMID- 8479382 TI - Focus groups: a useful research method in general practice. PMID- 8479383 TI - Protracted form of encephalitis with good outcome. AB - OBJECTIVE: To present four patients seen over a five-year period who developed severe protracted encephalitic illnesses but whose outcomes were favourable. CLINICAL FEATURES: Of the four patients, aged 18, 22, 34 and 19, three presented with acute psychosis, and all had a prolonged clinical course requiring intensive care management. One patient had residual generalised seizures and the other three recovered fully. No infective or toxic agent could be identified but viral encephalitis was considered most likely. OUTCOME: Despite the protracted courses, the outcomes were favourable. This is in contrast to the generally poor outcomes in encephalitis caused by established infective agents such as herpes simplex type 1. CONCLUSIONS: When the aetiology and hence the natural history of the encephalitis is unknown, long-term intensive support is appropriate. PMID- 8479384 TI - Endocarditis caused by Brucella melitensis. AB - OBJECTIVE: To describe the management of an uncommon but serious infection in Australia. CLINICAL FEATURES: A 25-year-old woman developed endocarditis after residence in Turkey and consumption of goat dairy products. Brucella melitensis was isolated from blood cultures. INTERVENTION AND OUTCOME: The valve remained infected after prolonged intravenous administration of trimethoprim sulfamethoxazole, gentamicin and rifampicin. Uncontrolled sepsis and worsening haemodynamic function necessitated valve replacement. To date the patient remains well while taking trimethoprim-sulfamethoxazole and rifampicin. CONCLUSION: Endocarditis due to Brucella spp. is uncommon in Australia. This infection is difficult to cure with antimicrobial therapy alone and early surgical intervention is advisable. PMID- 8479385 TI - Pulmonary arteriovenous malformation. Progressive enlargement with replacement of the entire right middle lobe in a patient with concomitant mitral stenosis. AB - OBJECTIVE: To present a case of pulmonary arteriovenous malformation (AVM) that showed progressive enlargement in a patient with concomitant rheumatic mitral stenosis. CLINICAL FEATURES: A 73-year-old woman first presented eight years ago because of an uncomplicated acute myocardial infarction. She was noted to have rheumatic mitral stenosis. Six years later, she developed symptomatic sick sinus syndrome for which a permanent pacemaker was implanted. Chest x-ray revealed new development of an opacity in the middle zone of the right lung. Two years later, she was admitted to hospital because of progressive dyspnoea. Chest x-ray showed further increase in size of the right middle zone opacity. OUTCOME: She died of cardiopulmonary failure on the 18th day in hospital. Autopsy revealed a pulmonary AVM, replacing the entire right middle lobe. CONCLUSION: The elevated pulmonary vascular resistance caused by mitral stenosis may have increased the preferential flow of blood through the AVM, leading to its rapid enlargement. Patients with concomitant pulmonary AVM and mitral stenosis need to be recognised, as close follow-up and early treatment may be desirable. PMID- 8479386 TI - Vaccination against influenza infection. Thoracic Society of Australia and New Zealand. PMID- 8479387 TI - Human fetal tissue for medical research. PMID- 8479388 TI - Recurrent episodes of confusion, headache and visual disturbance in a young woman. PMID- 8479389 TI - Kids play the safe way. PMID- 8479390 TI - Pregnancy from subzonally microinjected epididymal spermatozoa. PMID- 8479391 TI - Compensable psychiatric illness. PMID- 8479392 TI - Fatal Stevens-Johnson syndrome associated with a new non-steroidal anti inflammatory agent, tiaprofenic acid. PMID- 8479393 TI - Disarming the box-jellyfish. PMID- 8479394 TI - Awareness of the National Asthma Campaign. PMID- 8479395 TI - Child homicide--the extreme of child abuse. PMID- 8479396 TI - Child homicide--the extreme of child abuse. PMID- 8479397 TI - New directions for acute stoke therapy. PMID- 8479399 TI - Gap between approved indications and use of older drugs. PMID- 8479398 TI - Decisions in clinical management. PMID- 8479400 TI - Vigabatrin in the Sturge Weber syndrome. PMID- 8479401 TI - The history of studying the interactions of medical, surgical, and psychiatric conditions and their treatments. PMID- 8479402 TI - Organic and psychological sequelae of traumatic brain injury: the postconcussional syndrome in clinical practice. PMID- 8479403 TI - Psychiatric disorders complicating treatment of patients with pulmonary disease. AB - Treatment of pulmonary disease can be significantly complicated by the presence of psychiatric disorders. It is therefore essential to evaluate and understand the interaction of the pulmonary and psychiatric disorders in order to optimize patient care and management. PMID- 8479404 TI - Presentations and management of depression in medical-surgical patients. AB - Depression in medical-surgical patients has great impact on their well-being and medical condition. Although depression is like cancer, it is like a treatable cancer. If it is recognized and treated, the positive results can be dramatic and rewarding. PMID- 8479405 TI - Recognition and management of delirium in medical-surgical patients. PMID- 8479406 TI - Emotional aspects of sleep disorders: the case of obstructive sleep apnea syndrome. PMID- 8479407 TI - Biopsychosocial aspects of AIDS. PMID- 8479408 TI - Management of the psychiatric aspects of chronic noncancer pain. PMID- 8479409 TI - Depression syndromes in patients with Alzheimer's disease, Parkinson disease, and cerebral vascular accidents. PMID- 8479410 TI - Evaluation and care of the dementia patient. AB - Dementia is the result of a variety of factors that produce cognitive decline. While no cure exists for the majority of cases, treatment is available, and optimism for the future is reasonable. PMID- 8479411 TI - Specific psychotherapy approaches to medical-surgical patients. PMID- 8479412 TI - Management of psychiatric disorders in epileptic patients. PMID- 8479413 TI - Rates of cesarean delivery--United States, 1991. AB - Cesarean deliveries have accounted for nearly 1 million of the approximately 4 million annual deliveries in the United States since 1986 (Table 1). The cesarean rate in the United States is the third highest among 21 reporting countries, exceeded only by Brazil and Puerto Rico (1). This report presents data on cesarean deliveries from CDC's National Hospital Discharge Survey (NHDS) for 1991 and compares these data with previous years. PMID- 8479414 TI - Malaria among U.S. Embassy personnel--Kampala, Uganda, 1992. AB - The treatment and prevention of malaria in Africa has become a challenging and complex problem because of increasing drug resistance. Although the risk of acquiring malaria for U.S. citizens and their dependents stationed overseas generally has been low, this risk varies substantially and unpredictably. During May 1992, the Office of Medical Services, Department of State (OMS/DOS), and CDC were notified of an increased number of malaria cases among official U.S. personnel stationed in Kampala, Uganda. A review of the health records from the Embassy Health Unit (EHU) in Kampala indicated that 27 cases of malaria were diagnosed in official personnel from March through June 1992 compared with two cases during the same period in 1991. EHU, OMS/DOS, and CDC conducted an investigation to confirm all reported malaria cases and identify potential risk factors for malaria among U.S. Embassy personnel. This report summarizes the results of the investigation. PMID- 8479415 TI - FDA approval of use of a new Haemophilus b conjugate vaccine and a combined diphtheria-tetanus-pertussis and Haemophilus b conjugate vaccine for infants and children. PMID- 8479416 TI - Fatalities attributed to entering manure waste pits--Minnesota, 1992. AB - In August 1992, four farm workers in Minnesota died in two separate incidents after entering manure waste pits: two were poisoned by hydrogen sulfide gas, and two were asphyxiated. The Minnesota Fatality Assessment and Control Evaluation (FACE) program was notified of the incidents by the state Occupational Safety and Health Administration and the Minnesota Farming Health Project, respectively. This report summarizes the investigations of these two incidents by the Minnesota FACE program and CDC's National Institute for Occupational Safety and Health (NIOSH) FACE personnel. PMID- 8479417 TI - Update: investigations of persons treated by HIV-infected health-care workers- United States. AB - Previous reports have described transmission of human immunodeficiency virus (HIV) to five persons (patients A, B, C, E, and G) during receipt of care from an HIV-infected dentist in Florida and other investigations of patients who were treated by HIV-infected health-care workers (HCWs). This report updates these investigations and presents evidence that a sixth patient (patient I) became infected with HIV while receiving care at the Florida dental practice, the only practice in which HIV transmission from an infected HCW to patients has been documented. PMID- 8479418 TI - Fetal alcohol syndrome--United States, 1979-1992. AB - Fetal alcohol syndrome (FAS) is characterized by a variety of physical and behavioral traits that result from maternal alcohol consumption during pregnancy. Features of FAS include prenatal or postnatal growth deficiency, abnormal facial features, and central nervous system deficits. CDC's Birth Defects Monitoring Program (BDMP)--a national program to monitor congenital malformations--has collected data on the incidence of FAS among newborn infants since 1979. This report presents a rate for FAS in the United States using BDMP data from 1979 through 1992. PMID- 8479419 TI - A specific host factor binds at a cis-acting transcriptionally silent locus required for stability control of yeast plasmid pSR1. AB - A cis-acting locus, Z, of plasmid pSR1 functions in stable maintenance of the plasmid in the native host, Zygosaccharomyces rouxii. The Z locus was shown to be located in a 482 bp sequence in the 5' upstream region of an open reading frame, P, by subcloning various DNA fragments in a plasmid replicating via the ARS1 sequence of the Saccharomyces cerevisiae chromosome. Northern analysis revealed that the Z region is not transcribed in either the native host Z. rouxii or the heterologous host S. cerevisiae. The Z region is protected from micrococcal nuclease attack in Z. rouxii but not in S. cerevisiae, its protection depending on the product of the S gene encoded by pSR1. Gel retardation assays suggested that a factor present in nuclear extracts of Z. rouxii cells, irrespective of the presence or absence of a resident pSR1 plasmid, binds to a 111 bp RsaI-SacII sequence in the Z region. These findings suggest that a host protein binds to the Z locus and that the S product interacts with this DNA-protein complex and stabilizes pSR1. PMID- 8479420 TI - Signal transduction and sporulation in Bacillus subtilis: autophosphorylation of Spo0A, a sporulation initiation gene product. AB - Spo0A is a positive/negative transcriptional regulator that plays a very important role in sporulation initiation in Bacillus subtilis. The N-terminal amino acid sequence of Spo0A is homologous to that of regulator proteins of the two-component regulatory systems involved in signal transduction in bacteria. Phosphorylation of SpooA through a phosphorelay has been reported recently. In this study, we found that Spo0A is autophosphorylated in the presence of ATP and that an autophosphorylation-deficient Spo0A mutant is completely defective in initiating sporulation. These results suggest that Spo0A autophosphorylation is an essential event in the signal transduction process that controls sporulation in B. subtilis. PMID- 8479421 TI - Analysis of the Rhizobium meliloti exoH/exoK/exoL fragment: ExoK shows homology to excreted endo-beta-1,3-1,4-glucanases and ExoH resembles membrane proteins. AB - Nucleotide sequencing of a 4.15 kb DNA fragment from megaplasmid 2 of Rhizobium meliloti 2011 revealed the location of the genes exoH, exoK and exoL. The putative proteins encoded by these genes have molecular weights of 41, 30, and 44 kDa, respectively. The hydrophobicity profile of the ExoH amino acid sequence resembles that of transmembrane proteins. The predicted exoL gene product does not contain hydrophobic regions, indicating a cytoplasmic localization. The exoK gene product is characterized by a putative signal peptide and exhibits significant homology to endo-beta-1,3-1,4-glucanases of bacilli and Clostridium thermocellum. R. meliloti exoK mutants induced pink nodules and synthesized a reduced amount of exopolysaccharide (EPS). Colonies of this mutant showed a delay in the appearance of the Calcofluor white fluorescence. In addition, the formation of the characteristic halo was strongly delayed. R. meliloti exoL and exoH mutants induced pseudonodules. The exoH, but not the exoL mutant, synthesized an EPS that could be precipitated by cetyl pyridinium chloride (CPC) and also by ethanol. Plasmid integration mutagenesis revealed promoter regions preceding exoH, exoK and exoL. PMID- 8479422 TI - Differential expression of the psbA genes in the cyanobacterium Synechocystis 6803. AB - The 5' region and transcription initiation sites of the psbA-2 and psbA-3 genes of Synechocystis 6803 were determined. The otherwise highly homologous genes were shown to diverge significantly in the 5' noncoding regions. The transcription start site for the psbA-2 gene was mapped to position -49 upstream of the coding region and for the psbA-3 gene to position -88, i.e. 38 bp upstream of the psbA-2 transcription start point. Both genes exhibit promoter elements, which conform in sequence and position to Escherichia coli consensus motifs. The two genes share identical -35 sequences but differ in their -10 sequences. Primer extension analysis demonstrated that the psbA-2 and psbA-3 genes are differentially expressed, with > 90% of the total psbA transcripts being produced by the psbA-2 gene and the rest by the psbA-3 gene. Inactivation of the psbA-2 gene resulted in an eightfold up-regulation of the psbA-3 gene. The strikingly higher stability of the psbA transcripts in darkness compared to light, and the accumulation of a specific decay intermediate under dark conditions was reported previously. We show here that this dark-stability applies to both the psbA-2 and psbA-3 transcripts. The psbA-3 transcript did not appear to produce the processed intermediate, arguing for the involvement of the 5' non-coding region as a determinant in psbA transcript degradation. PMID- 8479423 TI - Isolation of temperature-sensitive aminoacyl-tRNA synthetase mutants from an Escherichia coli strain harboring the pemK plasmid. AB - The pem locus, which is responsible for the stable maintenance of the low copy number plasmid R100, contains the pemK gene, whose product has been shown to be a growth inhibitor. Here, we attempted to isolate mutants which became tolerant to transient induction of the PemK protein. We obtained 20 mutants (here called pkt for PemK tolerance), of which 9 were temperature sensitive for growth. We analyzed the nine mutants genetically and found that they could be classified into three complementation groups, pktA, pktB and pktC, which corresponded to three genes, ileS, gltX and asnS, encoding isoleucyl-, glutamyl- and asparaginyl tRNA synthetases, respectively. Since these amino-acyl-tRNA synthetase mutants did not produce the PemK protein upon induction at the restrictive temperature, these mutants could be isolated because they behaved as if they were tolerant to the PemK protein. The procedure is therefore useful for isolating temperature sensitive mutants of aminoacyl-tRNA synthetases. PMID- 8479424 TI - The plant hormone abscisic acid mediates the drought-induced expression but not the seed-specific expression of rd22, a gene responsive to dehydration stress in Arabidopsis thaliana. AB - Nine cDNA clones, corresponding to genes that are responsive to dehydration (named RD), have been isolated from Arabidopsis thaliana. The sequence of a putative protein encoded by one of the RD cDNA clones, RD22, exhibits considerable homology to an unidentified seed protein (USP) of Vicia faba. Northern analysis showed that RD22 mRNA is induced by salt stress as well as by water deficit but not by cold or heat stress. RD22 mRNA appeared after the application of abscisic acid (ABA), an indication that transcription of RD22 mRNA is induced by endogenous ABA, the production of which is triggered by drought and salt stress. The induction of RD22 mRNA by ABA was inhibited by cycloheximide. Thus, it appears that protein synthesis is required for the induction of this mRNA by ABA. By contrast, protein synthesis was not required for the ABA responsive induction RD29 mRNA, which corresponds to another dehydration responsive gene of A. thaliana. These results suggest that there are at least two mechanisms for the induction of dehydration-responsive genes by ABA. RD22 mRNA was also expressed during the early and middle stages of seed development, showing a pattern of expression similar to that of USP. The seed-specific expression of RD22 seems not to be regulated by ABA. Structural analysis of the RD22 genomic clone revealed that the structural gene (designated rd22) contains three introns, and only a single copy of the gene is present in the A. thaliana genome, while the gene for USP from V. faba is actually a family of genes with 10 to 20 members.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479425 TI - Two classes of isocitrate lyase genes are expressed during late embryogeny and postgermination in Brassica napus L. AB - We have analyzed the structure of genes encoding the glyoxylate cycle enzyme isocitrate lyase from Brassica napus L. and their expression during embryogeny and postgermination. Restriction mapping, nucleotide sequence, and DNA gel blot hybridization analyses of cDNA and genomic clones indicated that there are approximately six isocitrate lyase genes in the B. napus genome that can be divided into at least two subfamilies based upon their divergence in 5' and 3' untranslated regions. We showed previously that isocitrate lyase mRNA accumulates during late embryogeny and postgermination. Here, we present results which indicate that several isocitrate lyase genes are expressed at both stages of development. First, gene-specific probes were used to show that mRNAs encoded by representatives of both gene subfamilies accumulated in both late maturation stage embryos and in seedlings of B. napus. Second, a single B. napus isocitrate lyase gene, together with 3.5 kb and 1.4 kb of 5' and 3' flanking regions, respectively, was expressed in both embryos and seedlings of transgenic tobacco plants. The results indicated that accumulation of isocitrate lyase in late embryogeny and postgermination does not result from the alternate expression of distinct members of the gene family. PMID- 8479426 TI - At least four regulatory genes control sulphur metabolite repression in Aspergillus nidulans. AB - Mutations in four genes: sconA (formerly suA25meth, mapA25), sconB (formerly mapB1), sconC and sconD, the last two identified in this work, relieve a group of sulphur amino acid biosynthetic enzymes from methionine-mediated sulphur metabolite repression. Exogenous methionine has no effect on sulphate assimilation in the mutant strains, whereas in the wild type it causes almost complete elimination of sulphate incorporation. In both mutant and wild-type strains methionine is efficiently taken up and metabolized to S adenosylmethionine, homocysteine and other compounds, scon mutants also show elevated levels of folate-metabolizing enzymes which results from the large pool of homocysteine found in these strains. The folate enzymes appear to be inducible by homocysteine and repressible by methionine (or S-adenosylmethionine). PMID- 8479427 TI - Nonsense suppression in thymine-requiring strains of Escherichia coli is a consequence of altered folate metabolism. AB - Thymine-requiring strains of Escherichia coli suppress nonsense and frameshift mutants of T4 phage. We proposed that these mutants make errors during translation because of an imbalance in folate metabolism. A thymine-requiring strain grown under suppressing conditions has elevated levels of reduced folates. We tested the effect of either mutational blocks or the inhibition of various steps in folate biosynthesis on suppression. Conditions which prevent the accumulation of 5-methyl tetrahydrofolate inhibit suppression, suggesting that elevated levels of this folate are required for suppression. Furthermore, conditions that result in an accumulation in dihydrofolate inhibit suppression. PMID- 8479428 TI - Mutants of Ustilago maydis defective in production of one of two polypeptides of KP6 toxin from the preprotoxin. AB - Double-stranded RNA viruses of Ustilago maydis encode secreted killer toxins to which other cells of the same species and closely related species are sensitive. KP6 toxin consists of two polypeptides, alpha and beta, produced from a single precursor preprotoxin. In this work, we cloned complementary DNA for the toxin encoding segment of two of the KP6 nonkiller mutants NK3 and NK13 that secrete the beta and alpha polypeptides, respectively. Both sequence analysis of the cDNA clones and in vitro translation of the toxin-encoding double-stranded RNAs showed that both mutants can produce full-length preprotoxins. Cys51 in alpha is converted to Arg in NK3 and Thr25 and Lys42 in beta are changed to Pro and Arg, respectively, in NK13. Although alpha and beta are encoded in a single prepropolypeptide, only the beta polypeptide is secreted by NK3 and only the alpha polypeptide is secreted by NK13. This differential expression of peptides from one precursor is a unique phenomenon. Neither of the nonsecreted polypeptides accumulated in the cytosol. The possible effects of these mutations on preprotoxin folding and their consequences for toxin secretion are discussed. PMID- 8479429 TI - The cell cycle genes cdc22+ and suc22+ of the fission yeast Schizosaccharomyces pombe encode the large and small subunits of ribonucleotide reductase. AB - The cdc22+ gene of Schizosaccharomyces pombe is required early in the cell cycle, and its transcript varies in concentration in step with the cell cycle, with a peak level at the G1-S boundary. The sequences of the cdc22+ gene and of a multicopy suppressor of cdc22ts mutations, suc22+, have been determined. The cdc22+ open reading frame, which is interrupted in the genome by a single intron very close to its 5' end, encodes a protein of 811 amino acids, which has an amino acid sequence highly similar to that of the large subunit of ribonucleotide reductase from several species. The suc22+ gene contains an uninterrupted open reading frame of 391 amino acids, very similar to the sequence of the small subunit of ribonucleotide reductase. Disruption of either gene is lethal. Upstream of the cdc22+ coding region are seven short sequence elements similar to the recognition sequence for MluI, which are involved in regulating periodic transcription of the gene. Inhibition of DNA synthesis by hydroxyurea results in a several-fold increase in the level of the cdc22+ transcript. In contrast, hydroxyurea does not induce the 1.5 kb transcript of suc22+, but results in the induction of a 1.9 kb mRNA which hybridises to suc22+ DNA. PMID- 8479430 TI - A technique for targeted mutagenesis of the EF-Tu chromosomal gene by M13 mediated gene replacement. AB - A generally applicable system for targeted mutagenesis of a chromosomal sequence is described. The Escherichia coli tufA gene was mutated using a recombinant M13mp9 phage vector carrying a tuf gene. Integration via crossing over with the chromosomal tufA target gene produced an M13 lysogen. These lysogens were screened for resistance to kirromycin. The M13 phage carrying tufA mutations were efficiently retrieved by a genetic procedure. Genetic mapping was performed with the M13 vectors. The same recombinant M13 phage was used for mutagenesis, lysogen formation, gene replacement, retrieval, mapping and sequencing of kirromycin mutants. Three different mutations yielding resistance to kirromycin were found: two of these have previously been found and characterised, while the third mutation, Gly316-->Asp, is a new mutant. We also report the identification of a fourth kirromycin-resistant mutant, Gln124-->Lys. PMID- 8479431 TI - A study of integrative transformation in Schizosaccharomyces pombe. AB - Using the one-step gene disruption technique, we studied the effect of various parameters on the disruption frequency (percentage of homologous integrants) and transformation efficiency (number of transformants per microgram of input DNA) of integrative transformation in Schizosaccharomyces pombe. We used suc1 as the target gene for disruption and ura4 as the selectable marker. Our results are as follows. 1) Use of the strong adh1 promoter to drive the expression of ura4 did not affect the disruption frequency but modestly increased the transformation efficiency. 2) The transformation method had a profound effect, with the lithium acetate method yielding both a 10-fold higher disruption frequency compared to the protoplast method and a 5- to 10-fold higher transformation efficiency. 3) The presence of increasing amounts of non-homologous sequences at the ends of the transforming DNA decreased the disruption frequency by up to 5-fold but had no effect on the transformation efficiency. We also describe the use of the sup3-5 allele in an ade6-704 genetic background to discriminate between the products of homologous versus non-homologous integration, thereby promoting the identification of rare homologous integrants. PMID- 8479432 TI - Resistance in tomato to Xanthomonas campestris pv vesicatoria is determined by alleles of the pepper-specific avirulence gene avrBs3. AB - Bacterial spot disease of tomato and pepper caused by Xanthomonas campestris pv vesicatoria is prevented by resistance genes in the plant that match genes for avirulence in the bacterium. Based on DNA homology to the avirulence gene avrBs3, which induces the resistance response on pepper, we have isolated another avirulence gene from X. c. vesicatoria, designated avrBs3-2. This gene differs in specificity from avrBs3 in inducing the hypersensitive response on tomato but not on pepper. Sequence analysis of the avrBs3-2 gene revealed a high degree of conservation: the 3480 bp open reading frame contains an internal region of 17.5 nearly identical 102 bp repeat units that differ in their order from those present in the avrBs3 gene. The coding region is 97% identical to avrBs3 and expresses constitutively a 122 kDa protein, thus representing a natural allele of this gene. The previously isolated 1.7 kb avrBsP gene from X. c. vesicatoria is 100% identical to the corresponding avrBs3-2 sequence, indicating that these genes might be identical. Interestingly, derivatives of avrBs3-2 lacking the C terminal region and part of the repetitive region are still able to confer incompatibility in tomato. The avrBs3-2 gene is compared with the sequence of avrBs3 derivatives generated by deletion of repeat units that also have avirulence activity on tomato. Both genes, avrBs3 and avrBs3-2, are flanked by a 62 bp long inverted repeat, which prompts speculations about the origin of the members of the avrBs3 gene family. PMID- 8479433 TI - Cloning and analysis of the mating type genes from Cochliobolus heterostrophus. AB - Cochliobolus heterostrophus, a heterothallic Ascomycete, has a single mating type locus with two alternate forms called MAT-1 and MAT-2. MAT-1 was cloned by complementing a MAT-2 strain using a cosmid library from a MAT-1 strain and screening for a homothallic transformant. The cosmid recovered from this transformant was able to re-transform a MAT-2 strain to homothallism and MAT identity was proven by restriction fragment length polymorphism and conventional genetic mapping. All homothallic transformants could mate with either MAT-1 or MAT-2 strains, although the number of ascospores produced by self matings or crosses to MAT-2 strains was low. Progeny of selfed homothallic transformants were themselves homothallic. MAT-2 was cloned by probing a cosmid library from a MAT-2 strain with a fragment of insert DNA from a MAT-1 cosmid. A 1.5 kb subclone of either MAT-containing cosmid was sufficient to confer mating function in transformants. Examination of the DNA sequence of these subclones revealed that MAT-1 and MAT-2 contain 1297 bp and 1171 bp, respectively, of completely dissimilar DNA flanked by DNA common to both mating types. Putative introns were found (one in each MAT gene) which, when spliced out, would yield open reading frames (ORFs) that occupied approximately 90% of the dissimilar DNA sequences. Translation of the MAT-1 ORF revealed similarity to the Neurospora crassa MATA, Podospora anserina mat-, and Saccharomyces cerevisiae MAT alpha 1 proteins; translation of the MAT-2 ORF revealed similarity to the N. crassa MATa, P. anserina mat+, and Schizosaccharomyces pombe mat-Mc proteins. These gene products are all proven or proposed DNA binding proteins. Those with similarity to MAT-2 are members of the high mobility group. PMID- 8479434 TI - The Nicotiana tabacum genome encodes two cytoplasmic thioredoxin genes which are differently expressed. AB - A Nicotiana tabacum thioredoxin h gene (EMBL Accession No. Z11803) encoding a new thioredoxin (called h2) was isolated using thioredoxin h1 cDNA (X58527), and represents the first thioredoxin h gene isolated from a higher plant. It encodes a polypeptide of 118 amino acids with the conserved thioredoxin active site Trp Cys-Gly-Pro-Cys. This gene comprises two introns which have lengths of 1071 and 147 bp respectively, and three exons which encode peptides of 29, 41 and 48 amino acids, respectively. This thioredoxin h shows 66% identity with the amino acid sequence of thioredoxin h1 (X58527) and only around 35% with the choroplastic thioredoxins. The two thioredoxins, h1 and h2, do not have any signal peptides and are most probably cytoplasmic. Using the 3' regions of the mRNAs, two probes specific for thioredoxins h1 and h2 have been prepared. Southern blot analysis shows that thioredoxin sequences are present in only two genomic EcoRI fragments: a 3.3 kb fragment encodes h1 and a 4.5 kb fragment encodes h2. Analysis of the ancestors of the allotetraploid N. tabacum shows that thioredoxin h2 is present in N. sylvestris and N. tomentosiformis but that thioredoxin h1 is absent from both putative ancestors. Thus, the thioredoxin h1 gene has probably been recently introduced in to N. tabacum as a gene of agronomic importance, or linked to such genes. Northern blot analysis shows that both genes are expressed in N. tabacum, mostly in organs or tissues that contain growing cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479435 TI - Genetic and physical mapping of barley telomeres. AB - Barley (Hordeum vulgare L.) telomeres were investigated by means of pulsed field gel electrophoresis (PFGE) and in situ hybridization. In situ hybridization showed that a tandemly repeated satellite sequence has a subtelomeric location, and is present at thirteen of the fourteen chromosome ends. PFGE revealed that this satellite sequence is physically close to the telomeric repeat. Pulsed field gel electrophoresis was then used for segregation analysis and linkage mapping of several telomeric and satellite loci in a segregating doubled-haploid population. The telomeric repeat displayed a hypervariable segregation pattern with new alleles occurring in the progeny. Eight satellite and telomeric sites were mapped on an restriction fragment length polymorphism (RFLP)-map of barley, defining the ends of chromosome arms 1L, 2S, 3L, 4S, 4L, 5S and 6. One satellite locus mapped to an interstitial site on the long arm of chromosome 3. The physical location of this locus was confirmed by in situ hybridization to wheat/barley addition line 3. PMID- 8479436 TI - The A mating-type genes of the mushroom Coprinus cinereus are not differentially transcribed in monokaryons and dikaryons. AB - The A mating type factor of Coprinus cinereus regulates part of a developmental sequence that leads to the conversion of the asexual monokaryon into the fertile dikaryon. The A42 factor is a complex of seven genes, at least four of which are involved in determining the specificity of mating interactions. In this report we show that the A42 genes are constitutively expressed in both monokaryons and dikaryons. This has important implications with respect to intracellular recognition of a compatible mating, which requires an interaction between proteins already present within the cells of the mating partners, and for the subsequent maintenance of dikaryotic growth. PMID- 8479437 TI - The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. AB - The Drosophila Tumorous-lethal (Tum-l) mutation acts as an activated oncogene, causing hematopoietic neoplasms, overproliferation, and premature differentiation. Tum-l is a dominant mutation in the hopscotch (hop) locus, which is required for cell division and for proper embryonic segmentation. The Tum-l temperature-sensitive period for melanotic tumor formation includes most of larval and pupal development. PMID- 8479438 TI - Amplification and loss of repeat units of the human minisatellite MS1 integrated in chromosome III of a haploid yeast strain. AB - Minisatellites comprise arrays of tandemly repeated short DNA sequences which show extensive variation in repeat unit number. The mechanisms that underlie this length variation are not understood. In order to study processes influencing length changes of minisatellites, we integrated the human minisatellite MS1 into a haploid strain of the yeast Saccharomyces cerevisiae. Frequent spontaneous generation of MS1 alleles with new lengths were observed in this yeast strain. Hence it is concluded that recombination between members of a pair of homologous chromosomes is not a prerequisite for the generation of length changes in MS1 in yeast. PMID- 8479439 TI - Electrophoretic karyotypes of the elm tree pathogen Ophiostoma ulmi (sensu lato). AB - Pulsed field gel electrophoresis using OFAGE, TAFE, and CHEF systems has been used to more fully characterize karyotypic variation within the two closely related fungal species of Ophiostoma ulmi sensu lato. Twelve wild-type and laboratory strains, representing the less aggressive species O. ulmi and both of the biotypes of the more aggressive species O. novo-ulmi were studied and their karyotypes determined. Depending on the strain, a minimum of four to a minimum of eight chromosomal DNA bands were present that fall into three distinct size classes, with one exception. Strain CESS16K (O. novo-ulmi, North American aggressive subgroup) contains a unique chromosomal DNA band which comigrated near a Saccharomyces cerevisiae chromosome of 0.95 Mb. This unique band was the smallest O. ulmi s. l. chromosomal DNA observed. Seven of the twelve strains shared a common chromosomal DNA banding pattern, whereas each of the other five had a unique karyotype. There was no correlation between chromosome profile and species, as some O. novo-ulmi and O. ulmi strains shared common electrophoretic karyotypes. PMID- 8479440 TI - Individualization and estimation of relatedness in crocodilians by DNA fingerprinting with a Bkm-derived probe. AB - Individual-specific DNA fingerprints of crocodilians were obtained by the use of Bkm-2(8) probe. Pedigree analyses of Crocodylus palustris, C. porosus and Caiman crocodilus revealed that the multiple bands (22-23 bands with Aludigest) thus obtained were inherited stably in a Mendelian fashion. Unique fingerprints permitted us to identify individuals, assign parentage, and reconstruct the DNA profile of a missing parent. Average band sharing between unrelated crocodiles was found to be 0.37. Band sharing between animals of known pedigrees increased predictably with relatedness and provided a basis for distinguishing relatives from non-relatives. Similar results obtained in other species/genera, using the same probe, suggest that this approach may be applicable to all species of crocodilians, and could facilitate genetic studies of wild and captive populations. PMID- 8479441 TI - Effect of tandem repeated AUG codons on translation efficiency of eukaryotic mRNA carrying a short leader sequence. AB - The effect on translation of multiple copies of the initiation codon AUG at the initiation site in a eukaryotic mRNA carrying a short leader sequence was tested in translation experiments in vitro. DNA, corresponding to a chimeric mRNA sequence consisting of the 5' leader region of brome mosaic virus (BMV) RNA4 and the goat pre-alpha-lactalbumin mRNA sequence, was prepared and transcribed in vitro using SP6 RNA polymerase. Site-directed mutagenesis was carried out to change the sequence around the initiation codon AUG. In a wheat germ translation system, the yield of protein obtained using the mRNA with a duplication of the AUG codons at the initiation site was 1.6 times that achieved when only one AUG was present. The rate of formation of the 80S initiation complex was measured by the ribosome binding assay using cycloheximide. A good correlation was observed between the ability to form the complex and translation efficiency. PMID- 8479442 TI - Pseudomonas aeruginosa promoters which contain a conserved GG-N10-GC motif but appear to be RpoN-independent. AB - The proC gene of Pseudomonas aeruginosa encodes the constitutive delta 1 pyrroline 5-carboxylate reductase (the third enzyme of proline biosynthesis) and ranks among the numerous Pseudomonas genes which are poorly transcribed in Escherichia coli. The promoters of the proC gene were located by deletion mapping. The 5' ends of the proC transcripts originating from one promoter were determined by primer extension. This promoter has a GG-N10-GC motif with a 16 bp spacing between the GC doublet and the transcription start site. Such spacing is unusually long for sigma 54-dependent promoters. In rpoN mutants of P. aeruginosa and P. putida a proC'--'lacZ fusion was expressed at wild-type levels, suggesting that sigma 54 RNA polymerase is not involved in proC transcription. The expression of another P. aeruginosa gene, anr (for anaerobic regulation of nitrate respiration and anaerobic arginine degradation), also appeared to be independent of RpoN in Pseudomonas and occurred at a very low level in E. coli. The proC and anr promoters have sequence similarities in addition to the conserved GG--N10--GC motif and may also be related to some alg (alginate) promoters of P. aeruginosa. We propose that the proC and anr promoters are activated by proteins, including perhaps an alternative sigma factor, which are present in Pseudomonas but absent from E. coli. PMID- 8479443 TI - Molecular characterization of conventional and new repeat-induced mutants of nit 3, the structural gene that encodes nitrate reductase in Neurospora crassa. AB - Nitrate reductase of Neurospora crassa is a dimeric protein composed of two identical subunits, each possessing three separate domains, with flavin, heme, and molybdenum-containing cofactors. A number of mutants of nit-3, the structural gene that encodes Neurospora nitrate reductase, have been characterized at the molecular level. Amber nonsense mutants of nit-3 were found to possess a truncated protein detected by a specific antibody, whereas Ssu-1-suppressed nonsense mutants showed restoration of the wild-type, full-length nitrate reductase monomer. The mutants show constitutive expression of the truncated nitrate reductase protein; however normal control, which requires nitrate induction, was restored in the suppressed mutant strains. Three conventional nit 3 mutants were isolated by the polymerase chain reaction and sequenced; two of these mutants were due to the deletion of a single base in the coding region for the flavin domain, the third mutant was a nonsense mutation within the amino terminal molybdenum-containing domain. Homologous recombination was shown to occur when a deleted nit-3 gene was introduced by transformation into a host strain with a single point mutation in the resident nit-3 gene. New, severely damaged, null nit-3 mutants were created by repeat-induced point mutation and demonstrated to be useful as host strains for transformation experiments. PMID- 8479444 TI - A homologous gene-reporter system for the basidiomycete Schizophyllum commune based on internally deleted homologous genes. AB - Problems encountered in our attempts to achieve expression of heterologous genes, driven by ascomycetous regulatory sequences, in homobasidiomycetes led us to develop a gene-reporter system based on the expression of homologous genes in Schizophyllum commune. Internal deletions were made in the coding sequences of the regulated Sc4 gene and the constitutively expressed GPD gene. After introduction of these constructs into S. commune it was found that the expected truncated transcripts were produced. The internally deleted Sc4 gene, containing 1140bp of upstream and 200 bp of downstream sequences, was only expressed in dikaryons at the time of fruiting (as was the resident Sc4 gene) but not at all in monokaryons, indicating that the construct contained all regulatory sequences necessary and sufficient to confer control by the mating-type genes and expression during fruiting. The internally deleted GPD gene, containing 1300 bp of upstream and 150 bp of downstream sequences, was expressed both in monokaryons and dikaryons at levels similar to those of the resident GPD gene, indicating that all sequences necessary for proper expression were present. This reporter gene system may be applicable to the analysis of cis-regulatory sequences of these genes. Furthermore, heterologous genes may be inserted into the well expressed GPD deletion construct to obtain expression of such genes in S. commune and possibly in other homobasidiomycetes. PMID- 8479445 TI - Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni. AB - An ATP-diphosphohydrolase (EC 3.6.1.5) was identified in the tegumental fraction isolated from Schistosoma mansoni worms. Both ATP and ADP were hydrolyzed to AMP at similar rates by the enzyme. Other nucleotides were also degraded by the tegument enzyme, revealing a broad substrate specificity. Electrophoretic separation of tegumental proteins under non-denaturing conditions followed by addition of ATP or ADP as substrate revealed a single band of activity with similar mobility. In addition, similar heat-inactivation profiles were obtained for ATPase or ADPase activities, indicating that a single enzyme is responsible for degrading both nucleotides. The enzyme was not inhibited by vanadate, levamisole, tetramisole, ouabain or sodium azide. The ADPase activity was not affected by adenosine (5')-pentaphospho-(5')-adenosine (Ap5A) or by an excess of glucose and hexokinase used as an ATP-trapping system, thus excluding the presence of any significant adenylate kinase activity. The ATP-diphosphohydrolase displayed micromolar affinities for both Mg2+ and Ca2+, and the calcium-activated enzyme was inhibited by millimolar Mg2+. In intact live worms a calcium phosphate precipitate was formed on the outer tegumental surface upon incubation of the worms with either ATP or ADP, indicating the ectolocalization of this enzyme. In addition, ultrastructural histochemical localization of the enzyme was obtained. A distinct deposition of lead phosphate granules on the outer surface of the tegument was observed by electron microscopy, in the presence of either ATP or ADP as substrate. It is suggested that the ATP-diphosphohydrolase could regulate the concentration of purine nucleotides around the parasites and hence enable them to escape the host hemostasis by preventing ADP-induced platelet activation. PMID- 8479446 TI - A developmentally regulated gene of Echinococcus granulosus codes for a 15.5 kilodalton polypeptide related to fatty acid binding proteins. AB - A stage-specific expressed gene has been isolated from a cDNA expression library of Echinococcus granulosus protoscolices. The isolated clone contains the complete coding sequence. The corresponding protein (EgDf1) has a molecular weight of 15.5 kDa and is expressed at the tegumental level in the protoscolices, being undetectable in the germinal layer of the metacestode. This protein shares an important homology with a family of low-molecular weight proteins involved in the binding of hydrophobic ligands. This family includes a protein of Schistosoma mansoni (Sm 14) that has immunoprotective activity in rodents. Histochemical and metabolic data already reported for E. granulosus suggest that EgDf1 could be a molecular marker for early events in the process of protoscolex differentiation. PMID- 8479447 TI - Role of acidic compartments in Trypanosoma brucei, with special reference to low density lipoprotein processing. AB - In the bloodstream form of Trypanosoma brucei, specific receptors mediate the endocytosis of host low-density lipoprotein particles. We have explored the fate of ligand and receptor with a biochemical approach, using inhibitors of the endocytotic apparatus. The weak base chloroquine rapidly accumulates in trypanosomes, its uptake is prevented by the proton ionophore monensin, and it induces the swelling of intracellular vacuoles, indicating that their content is acidic. Cell-associated LDL is rapidly degraded into intermediately sized fragments and TCA-soluble material that can be recovered in cell extracts and extracellular medium. Chloroquine, leupeptin and E64, but not PMSF, efficiently prevent LDL proteolysis, suggesting that degradation occurs in those acidic compartment(s) and is mediated by thiol-protease(s). Both monensin and chloroquine decrease the number of LDL receptors exposed at the cell surface, a phenomenon amplified in the presence of LDL. This provides indirect evidence that internalised LDL receptors are recycled at a rate which is slowed down by receptor occupancy and by agents that impair acidification of the endocytic organelles. Finally, chloroquine decreases by half the growth rate of procyclic trypanosomes in vitro at 5 micrograms ml-1. At 40 mg kg-1 per day, it also slows down the increase in parasitaemia and prolongs the survival time of infected mice by up to 2 days. PMID- 8479448 TI - Selective import of nuclear-encoded tRNAs into mitochondria of the protozoan Leishmania tarentolae. AB - The trypanosomatid mitochondrial genome does not encode tRNA genes at all and experimental evidence obtained with Leishmania tarentolae shows that tRNAs in mitochondria represent a selected set of imported nuclear-encoded tRNAs. In this paper we present the data showing that tRNAs derived from the clustered genomic tRNA genes are invariably imported into mitochondria, while tRNA from the solitary gene is not. By sequencing a cosmid DNA clone of L. tarentolae genomic DNA, we have identified a 1.5-kb subclone encoding a duplicate set of the closely linked tRNA(Tyr) (GTA) and tRNA(Thr) (AGT) genes. Northern analysis shows that these tRNAs are imported into mitochondria. In contrast, when the tRNA gene [tRNA(Gln) (CUG)] located alone in a 40-kb DNA fragment was examined, the corresponding tRNA was not detected in the mitochondrion. This "loner" tRNA gene is highly unusual since the 3'-flanking putative RNA polymerase III transcription termination signal sequence is characterized by a long string of 8 Ts followed by an A and a stretch of 7 Cs, while all other trypanosomatid tRNA genes whose tRNA transcripts are imported are terminated by a possible transcription termination signal of only 4-6 Ts. Whether the correlation found between the gene organization and tRNA-import characteristics is of general significance needs to be investigated further. A simple computer analysis presented in this paper rules out the possibility that tRNAs found in the trypanosomatid mitochondrion are the products of the U-addition type 'RNA editing' of maxicircle DNA. PMID- 8479449 TI - A gene encoding a 69-kilodalton major surface protein of Giardia intestinalis trophozoites. AB - A gene encoding a 68.5-kDa trophozoite surface protein (TSP11) of the Australian Giardia intestinalis (syn. G. lamblia) isolate, Ad-1, has been cloned from a genomic expression library screened with an antiserum specific for 3 major surface antigens. Sequence analysis of two overlapping genomic fragments identified a single open reading frame that contained no introns and predicted a cysteine-rich, 667-residue polypeptide with features common to other trophozoite surface proteins. These include the presence of 27 copies of the 4-amino acid Cys X-X-Cys motif, an N-terminal signal sequence and a highly conserved, hydrophobic C-terminal segment. Transcripts from the tsp11 gene were detected as a single band on Northern blots using total RNA extracted from Ad-1 trophozoites. Primer extension analysis indicated that the mRNA has a 5' untranslated region of only 5 nt, similar to the very short (1-6 nt) leader sequences reported for other Giardia mRNAs. A large portion of the promoter distal segment of tsp11 has homology with tsa417, a gene encoding a 72.5-kDa trophozoite surface antigen of the Afghanistan-derived G. intestinalis isolate, WB [13]. PMID- 8479450 TI - Design of Onchocerca DNA probes based upon analysis of a repeated sequence family. AB - Repeated DNA sequences have been instrumental in the development of DNA probes for many different parasites. Isolation of such DNA probes has generally been accomplished by differential screening of genomic libraries with total genomic DNA preparations. In the current work, a rational design strategy is presented for the development of oligonucleotide probes based upon repeated sequence families. A repeated sequence family present in the genome of Onchocerca parasites, designated O-150, has been amplified from various samples of genomic DNA using PCR. DNA sequence analysis of the resulting PCR products demonstrated that the sequences may be arranged into clusters within which the individual sequences are identical or nearly identical. Differences among the cluster consensus sequences have been exploited to explain the specificities of previously isolated O-150 based probes and to develop two new oligonucleotide probes. One of these probes hybridizes specifically to Onchocerca volvulus O-150 PCR products, while the second hybridizes specifically to O-150 PCR products from the closely related bovine parasite O. ochengi. These oligonucleotide probes have been used to characterize Onchocerca infective larvae isolated from wild caught infected flies in West Africa. Because repeated sequence families are a common feature of most genomes, including those of parasites, this method should be applicable to the rational design of oligonucleotide probes for other parasitic infections. PMID- 8479451 TI - Characterization of a surface metalloprotease from Herpetomonas samuelpessoai and comparison with Leishmania major promastigote surface protease. AB - The monogenetic kinetoplastid protozoan parasite Herpetomonas samuelpessoai expresses a surface-exposed metalloprotease. Comparable to the Leishmania promastigote surface protease, or PSP, the protease of Herpetomonas is active at the surface of fixed and live organisms, and both enzymes display an identical cleavage specificity toward a nonapeptide substrate. The protease was enriched 440 times by partition into Triton X-114 followed by 2 steps of anion exchange chromatography. The 56-kDa enzyme is inhibited by the metal chelator 1,10 phenanthroline and is susceptible to cleavage by glycosyl-phosphatidylinositol phospholipase C (GPI-PLC). The conservation of an identical surface protease activity in these monogenetic and digenetic trypanosomatids suggests that the enzyme has a physiological function in the promastigote (insect) stage of these parasites. PMID- 8479452 TI - Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. AB - Genus- and species-specific sequences are present within the small subunit ribosomal RNA genes of the four human malaria parasites. Oligonucleotide primer pairs specific to each species were designed for specific amplification by the Polymerase Chain Reaction (PCR), to detect each malaria species. DNA equivalent to 5 microliters of blood was sufficient for the detection of each of the species. Blood samples obtained from 196 patients attending a malaria clinic in Trad province (Thailand) were analyzed. Detection and identification of the parasites, solely by electrophoretic analysis of the PCR products, has proven to be more sensitive and accurate than by routine diagnostic microscopy. A high proportion of mixed species infections were brought to light by the PCR assay. Implications for medical treatment and epidemiological studies are discussed. PMID- 8479453 TI - Purification and partial characterization of an acid proteinase from Dirofilaria immitis. AB - An acid proteinase of Dirofilaria immitis worms was purified 437-fold by gel filtration on Sephadex G-75 followed by pepstatin-agarose gel affinity chromatography. The enzyme with a molecular weight of 42,000 and specific activity of 384 units (mg protein)-1 was homogeneous as judged by both affinity chromatography and SDS-polyacrylamide gel electrophoresis. However, polyacrylamide disc electrophoresis at pH 8.9 revealed that the enzyme is composed of 5 multiforms, all carrying proteinase activity. Optimum pH of the enzyme was in the range of pH 2.8-3.4, and its isoelectric point ranged between 5.8 and 6.4. The purified proteinase showed a potent activity against hemoglobin and myoglobin releasing acid soluble peptides, but not free amino acids. Complete inhibition of the proteolytic activity by pepstatin in the order of 10(-7) M strongly suggests that the enzyme belongs to the carboxyl-proteinase family. PMID- 8479454 TI - Molecular cloning of an echinococcal microtrichal antigen immunoreactive in Echinococcus multilocularis disease. AB - A cDNA expression library of the larval stage of the cestode worm Echinococcus multilocularis has been established in the phage lambda ZAPII system. By immunoscreening with pooled sera from patients with alveolar echinococcosis an immunoreactive clone, termed pEM13, was isolated. EM13 was expressed using the expression vector pGEX-3X, resulting in the synthesis of a glutathione S transferase fusion protein. 82% of the sera from 28 patients suffering from E. multilocularis disease had antibodies against EM13, whereas none of the 55 sera obtained from Echinococcus granulosus-infected patients and none of the 15 sera from patients with other helminthic infections reacted with recombinant EM13. By use of a polyclonal rabbit anti-EM13 hyperimmune serum native EM13 protein could be detected only in the protoscolices of E. multilocularis, but not in E. granulosus larvae or hydatid fluid. Immunoelectron microscopy suggested that EM13 is located in the microtriches on the surface of the larvae. In contrast, EM13 mRNA could be detected by Northern blot analysis in both E. multilocularis and E. granulosus larval RNA preparations. Nucleotide and amino acid sequence analysis of a cDNA clone coding for the corresponding antigen of E. granulosus larvae, termed EG13, revealed a 21-bp insertion, a 51-bp deletion and additional 22 nucleotide exchanges resulting in a 96.3% identity at the nucleotide sequence level and a 96.6% identity at the amino acid sequence level to the coding region of the cDNA pEM13. Cross-reactivity of the polyclonal anti-EM13 serum with the recombinant EG13 indicates a posttranscriptional regulation mechanism, resulting in an EG13 negative phenotype in E. granulosus. PMID- 8479455 TI - Characterization of a benzyl-phenoxy-ethanamine binding protein in Trypanosoma equiperdum and the possible relation between binding affinity and trypanocidal activity. AB - A new family of benzyl-phenoxy-ethanamine derivatives has been assayed for trypanocidal activity. Using tritiated morpholino-benzyl-phenoxy-ethanamine as a probe, it is shown that this ligand is able to bind specifically to a protein contained in extracts of Trypanosoma equiperdum. The binding is saturable and of high affinity (KD = 4 nM: Bmax = 200 fmol (mg protein)-1). The in vitro activities of the investigated compounds against this parasite correlate with their affinities to the putative binding site. Moreover, using an azido functionalized morpholino-benzyl-phenoxyethanamine as photoprobe a major M(r) = 40,000 protein was specifically revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. This molecular weight corresponds with the previously observed value determined for the antioestrogen binding site protein of rat liver which has been shown to specifically bind antioestrogens of the triphenylethylene family and phenoxyethanamine derivatives. PMID- 8479456 TI - Chitinolytic activities in Heligmosomoides polygyrus and their role in egg hatching. AB - The occurrence of chitin in the eggshell of Heligmosomoides polygyrus has been determined by histochemical and biochemical techniques. Approximately 5% of the egg dry weight was chitin. Staining with Calcofluor white showed the chitin in the eggshell to be more accessible to the stain after hatching or rupturing of the eggshell. Chitinolytic activity has been detected using fluorescent substrates in extracts of adult males (at low levels), females and eggs. Enzyme activity in situ, within the developing larvae, was visualised with the same substrates. It was localized in discrete granules about 1 micron in diameter which occurred as groups in areas of about 5 microns in diameter, in the posterior third of the larvae. The chitinolytic activity in the eggs increased with the age of the egg and was released into the medium when the eggs hatched. The chitinase activities were very sensitive to inhibition by allosamidin, a specific chitinase inhibitor, with an IC50 for the crude egg extract of 2.2 nM. However, treatment of eggs with 250 microM allosamidin resulted in a slowing but not cessation of egg hatching. PMID- 8479457 TI - Characterization of the mRNA encoding a proline-rich 37-kilodalton glycoprotein from the excretory-secretory products of Trichostrongylus colubriformis. AB - A glycoprotein, with apparent molecular weight in SDS-polyacrylamide gels of 37 kDa, has been isolated from the excretory-secretory (ES) products of the adult stage of Trichostrongylus colubriformis, a parasitic nematode. This protein is the major ES product recognized in immunoblots by lymph from a naturally infected sheep. A synthetic oligonucleotide, based on peptide sequence data from a digest of the purified protein was used to successfully screen a cDNA library. A cDNA clone was isolated which encoded a presumptive protein precursor of 220 amino acids that contained a 63 amino acid region of which more than 35% of the residues were proline, three peptide sequences determined from the natural component, and three potential N-glycosylation sites, consistent with the protein being isolated from the lectin-bound fraction of the adult ES products. The presumptive, processed, amino terminus encoded by the cDNA clone was preceded by a signal-like, hydrophobic-rich region of 16 amino acids. PMID- 8479458 TI - Cloning and characterization of a vacuolar ATPase A subunit homologue from Plasmodium falciparum. AB - The distribution of the antimalarial drug chloroquine is determined to a significant extent by a transvacuolar pH gradient in Plasmodium falciparum. A proton pump similar to the vacuolar ATPase found in many cell types has been suggested to maintain a pH gradient across the membranes of acidic compartments in the parasite. In order to understand and define the components involved in the mechanism of acidification of parasite vesicles, we have cloned and characterized a gene, designated VAP-A, encoding a P. falciparum homologue of the catalytic A subunit of the vacuolar ATPase. The VAP-A gene encodes a polypeptide of 611 amino acids which shows between 56 to 61% amino acid identity over its entire length with the sequences of vacuolar ATPase A subunits from several species. The VAP-A gene exists as a single copy gene on P. falciparum chromosome 13 and gives rise to a transcript of 3.7 kb. Antibodies raised against a VAP-A gene segment expressed in Escherichia coli react specifically with a 67-kDa polypeptide, consistent with the size predicted from the sequence and with the size of the corresponding polypeptide in other organisms. The 67-kDa protein is present throughout the asexual erythrocytic cycle and is expressed at similar levels in 5 P. falciparum isolates of differing chloroquine sensitivity. Sequence analysis of the coding region of the VAP-A gene from 2 chloroquine-sensitive and 3 chloroquine-resistant isolates has shown no changes that are linked to chloroquine resistance. Therefore, a proposed chloroquine resistance-linked vacuolar acidification defect does not involve mutations in the VAP-A gene in the isolates we have studied. PMID- 8479459 TI - Cloning and characterization of differentially expressed genes from in vitro grown 'amastigotes' of Leishmania donovani. AB - Leishmanial parasites routinely undergo cyclic differentiation from promastigotes to amastigotes during their life cycle. This process involves both morphological and macromolecular changes. To study such changes, we used a axenic culture system which permits the continuous generation and cycling of Leishmania donovani from promastigotes to 'amastigotes' in vitro. cDNA libraries were constructed from poly(A)+ RNA isolated from both the pro- and amastigote forms. Using differential cDNA hybridization techniques, 3 unique cDNAs clones (P17, A41 and A45) were isolated from the amastigote library. To assess whether these clones were differentially expressed by the pro-or 'amastigotes' forms, they were hybridized to RNA isolated from each of these parasite forms in Northern and slot blots. Results of these analyses showed that 'amastigotes' had approx. 2-fold higher levels of the A41 and A45 RNAs compared to the promastigotes. Conversely, promastigotes showed approx. 2-fold higher levels of the P17 RNA than 'amastigotes'. Nucleotide sequence analysis and comparison with those in Gene bank, revealed that the 3 cDNAs represent unique leishmanial genes. Comparison of the deduced amino acid sequences revealed that P17 open reading frame (ORF) had significant similarity with a soybean ribosomal protein S11; A41 ORF with a Bacillus subtilis spore germination gene (gerC) and A45 ORF with yeast stress inducible protein (STI1). It is of interest to note that, of the 3 cDNAs identified, the A45-encoded protein was recognized by sera from patients with clinically active visceral leishmaniasis and was encoded by a single copy gene. PMID- 8479460 TI - Cloning and expression of the gene for Plasmodium falciparum transmission blocking target antigen, Pfs230. PMID- 8479461 TI - Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. AB - BACKGROUND: The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. METHODS AND RESULTS: We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively. CONCLUSIONS: The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis. PMID- 8479462 TI - Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. AB - BACKGROUND AND METHODS: Irregular disfiguring skin hyperpigmentation due to inflammation may develop in black persons. We investigated the treatment of this hyperpigmentation with topical tretinoin (0.1 percent retinoic acid cream). Fifty four subjects completed a 40-week randomized, double-blind, vehicle-controlled study. Twenty-four subjects applied tretinoin daily to the face, arms, or both areas, and 30 subjects applied vehicle cream. At base line and after 40 weeks of treatment, each subject's post-inflammatory hyperpigmented lesions and normal skin were assessed by clinical and colorimetric evaluations and by analysis of biopsy specimens. RESULTS: The facial post-inflammatory hyperpigmented lesions of the tretinoin-treated subjects were significantly lighter after the 40 weeks of therapy than those of the vehicle-treated subjects (P < 0.001); overall improvement was first noted after four weeks of tretinoin treatment. At the end of treatment, colorimetry demonstrated a 40 percent lightening of the lesions toward normal skin color in the tretinoin-treated lesions, as compared with an 18 percent lightening in vehicle-treated lesions (P = 0.05). The epidermal melanin content in the lesions decreased by 23 percent with tretinoin and by 3 percent with vehicle (P = 0.24). Normal skin was minimally lightened by tretinoin as compared with vehicle, according to both clinical evaluation (0.1 vs. -0.1 unit change on an 8-point scale; P = 0.055) and colorimetry (P < 0.001). Retinoid dermatitis developed in 12 of the 24 tretinoin-treated subjects who completed the study (50 percent) and in 1 tretinoin-treated subject who withdrew from the study, but diminished as the study progressed. CONCLUSIONS: Topical application of tretinoin significantly lightens post-inflammatory hyperpigmentation and, to a clinically minimal but statistically significant degree, lightens normal skin in black persons. PMID- 8479463 TI - Vitamin E consumption and the risk of coronary disease in women. AB - BACKGROUND: Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis. METHODS: In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease). RESULTS: As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95 percent confidence interval, 0.38 to 0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multi vitamins). CONCLUSIONS: Although these prospective data do not prove a cause-and effect relation, they suggest that among middle-aged women the use of vitamin E supplements is associated with a reduced risk of coronary heart disease. Randomized trials of vitamin E in the primary and secondary prevention of coronary disease are being conducted; public policy recommendations about the widespread use of vitamin E should await the results of these trials. PMID- 8479464 TI - Vitamin E consumption and the risk of coronary heart disease in men. AB - BACKGROUND: The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. METHODS: In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. RESULTS: After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. CONCLUSIONS: These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies. PMID- 8479465 TI - Brief report: shock and multiple-organ dysfunction after self-administration of Salmonella endotoxin. PMID- 8479467 TI - Pathogenetic mechanisms of septic shock. PMID- 8479466 TI - Recent advances in pulmonary medicine (2) PMID- 8479468 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 20-1993. A 23-year-old woman with a rapidly enlarging intraoral mass after a tooth extraction. PMID- 8479469 TI - Chronic pancreatitis and pancreatic cancer. PMID- 8479470 TI - Tretinoin (retinoic acid) revisited. PMID- 8479471 TI - The American Health Security Act. A single-payer proposal. PMID- 8479472 TI - Actual versus self-reported intake and exercise in obesity. PMID- 8479473 TI - Actual versus self-reported intake and exercise in obesity. PMID- 8479474 TI - Actual versus self-reported intake and exercise in obesity. PMID- 8479475 TI - Actual versus self-reported intake and exercise in obesity. PMID- 8479476 TI - Massive obesity simulating lymphedema. PMID- 8479477 TI - Pancreatic and islet transplantation for diabetes. PMID- 8479478 TI - Pancreatic and islet transplantation for diabetes. PMID- 8479479 TI - Predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings. PMID- 8479480 TI - High-dose erythropoietin for unstable hemoglobin Burke in a patient receiving hemodialysis. PMID- 8479481 TI - Clinical problem-solving: sounds in the attic. PMID- 8479483 TI - Clinical problem-solving: sounds in the attic. PMID- 8479482 TI - Clinical problem-solving: sounds in the attic. PMID- 8479485 TI - HMOs and physicians without board certification. PMID- 8479484 TI - State-by-state pharmaceutical formulations? PMID- 8479486 TI - Abdominal pain after taking ursodiol. PMID- 8479487 TI - Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. AB - BACKGROUND AND METHODS: The combination of mifepristone (RU 486) and a prostaglandin analogue given either intramuscularly or intravaginally is effective in terminating early pregnancy, but the prostaglandin component of the regimen is cumbersome to administer and has side effects. We conducted two studies to determine the efficacy of 600 mg of mifepristone followed by a small dose of misoprostol, an orally active prostaglandin E1 analogue, for the same purpose. In the first study, 505 women who had had amenorrhea for less than 50 days received 400 micrograms of misoprostol 48 hours after receiving mifepristone, if the pregnancy was not terminated within that period. In the second study, 390 women initially received the same treatment, but if the pregnancy was not terminated within four hours after the administration of misoprostol, they were offered an additional 200-micrograms dose of misoprostol. RESULTS: In study 1, the rate of success (termination of pregnancy and complete expulsion of the conceptus) was 96.9 percent (95 percent confidence interval, 94.1 to 97.7 percent)--similar to the success rate of approximately 95 percent for mifepristone followed by the intramuscular or intravaginal administration of prostaglandin. Abortion occurred in 2.9 percent of the women within 48 hours after the administration of mifepristone, in 60.9 percent within 4 hours after the administration of misoprostol, and in 33.2 percent thereafter. The failures included ongoing pregnancies in four women (0.8 percent) and incomplete abortions in nine (1.8 percent); two other women (0.4 percent) required vacuum aspiration for prolonged uterine bleeding. In study 2, pregnancy was terminated in 5.5 percent of the women before the administration of misoprostol and within four hours after the first dose of misoprostol in 69.1 percent. Among the 71 women who received a second dose of misoprostol, 67 had complete abortions, 2 had partial retention of the conceptus, 1 had synechia with ongoing pregnancy, and 1 had an ectopic pregnancy. One ongoing pregnancy, which was terminated by vacuum aspiration, was recorded among the 27 women who declined to take the second dose of misoprostol. The overall rate of success of the regimen with the optional second dose of misoprostol was 98.7 percent (95 percent confidence interval, 96.8 to 99.5 percent). No woman had any serious adverse event. CONCLUSIONS: The combination of mifepristone and misoprostol is effective for the termination of early pregnancy in terms of success, tolerance, safety, and practicality. PMID- 8479488 TI - Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group. AB - BACKGROUND: Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis. METHODS: We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter). RESULTS: In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis. PMID- 8479489 TI - Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. AB - BACKGROUND: Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. METHODS: We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). RESULTS: Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects. PMID- 8479490 TI - Brief report: a molecular defect in the vasopressin V2-receptor gene causing nephrogenic diabetes insipidus. PMID- 8479491 TI - Brief report: a mutation in the vasopressin V2-receptor gene in a kindred with X linked nephrogenic diabetes insipidus. PMID- 8479492 TI - Hormonal contraception. PMID- 8479493 TI - Case records of the Massachusetts General Hospital. Weekly Clinicopathological Exercises. Case 21-1993. A 71-year-old man with a rash and severe sensorimotor neuropathy. PMID- 8479494 TI - Mifepristone (RU 486) in the United States. What does the future hold? PMID- 8479495 TI - Molecular insights into diabetes insipidus. PMID- 8479496 TI - Treatment of Gaucher's disease. PMID- 8479497 TI - Treatment of Gaucher's disease. PMID- 8479498 TI - Treatment of Gaucher's disease. PMID- 8479499 TI - Treatment of Gaucher's disease. PMID- 8479500 TI - Treatment of Gaucher's disease. PMID- 8479501 TI - Treatment of Gaucher's disease. PMID- 8479502 TI - Polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus. PMID- 8479503 TI - Polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus. PMID- 8479504 TI - Prevention and treatment of Pneumocystis pneumonia. PMID- 8479505 TI - More things that go bang in the night. PMID- 8479507 TI - Facial palsy in Lyme disease. PMID- 8479506 TI - Error in chemotherapy dosages. PMID- 8479508 TI - Compulsory payment for unwanted treatment. PMID- 8479509 TI - Syncope after eating. PMID- 8479510 TI - Physician-assisted suicide--Michigan's temporary solution. PMID- 8479511 TI - Canadian study fuels move to limit rise in drug prices. PMID- 8479512 TI - 15 drug companies to share data on AIDS therapies. PMID- 8479513 TI - Population control. PMID- 8479514 TI - Cancer. A death in the life of p53. PMID- 8479515 TI - Structural biology. Picture an enzyme at work. PMID- 8479516 TI - Universal tree of life. PMID- 8479517 TI - Universal tree of life. PMID- 8479518 TI - The pathogenesis of atherosclerosis: a perspective for the 1990s. AB - Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation. PMID- 8479519 TI - Interfacial activation of the lipase-procolipase complex by mixed micelles revealed by X-ray crystallography. AB - The three-dimensional structure of the lipase-procolipase complex, co crystallized with mixed micelles of phosphatidylcholine and bile salt, has been determined at 3 A resolution by X-ray crystallography. The lid, a surface helix covering the catalytic triad of lipase, adopts a totally different conformation which allows phospholipid to bind to the enzyme's active site. The open lid is an essential component of the active site and interacts with procolipase. Together they form the lipid-water interface binding site. This reorganization of the lid structure provokes a second drastic conformational change in an active site loop, which in its turn creates the oxyanion hole (induced fit). PMID- 8479520 TI - Kinship affects morphogenesis in cannibalistic salamanders. AB - Inclusive fitness theory predicts that organisms can often increase their fitness by helping relatives. Indeed, many animals modify their behaviour towards kin in a fashion consistent with theory. Morphogenesis may also be sensitive to kinship environment, especially in species that facultatively produce distinct morphs that differ in their ability to harm relatives, such as those that produce alternative cannibalistic and non-cannibalistic phenotypes. We tested this hypothesis by examining whether consanguinity affected the probability that structurally distinctive cannibal morphs would develop in larval Arizona tiger salamanders (Ambystoma tigrinum nebulosum). We report here that when tiger salamander larvae are reared in mixed-brood groups they are significantly more likely to develop the cannibal morphology and at an earlier age than siblings reared in pure-sibship groups. In general, morphogenesis may be responsive to kinship in any species that facultatively develops structures that can be used against conspecifics as weaponry. PMID- 8479521 TI - A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. AB - Extracellular deposition of amyloid beta-protein (beta-AP), or A4 protein (M(r) 4,000), is associated with Alzheimer's disease and with Down's syndrome (trisomy for chromosome 21). The large membrane-bound precursor protein (APP) of beta-AP is normally cleaved within the beta-AP region by a putative proteinase (APP secretase) to release its extracellular portion; beta-AP is produced by an alternative proteolytic processing. Here we demonstrate that APP contains a proteinase inhibitor domain for the matrix metalloproteinase gelatinase A, which is located in the C-terminal glycosylated region of the secretory forms of APP. In addition, we show that the gelatinase has an APP secretase-like activity, which hydrolyses the Lys16-Leu17 bond in the beta-AP sequence. Our results indicate that the proteinase inhibitor domain of APP and gelatinase A may be involved in the formation of beta-AP. PMID- 8479522 TI - p53 is required for radiation-induced apoptosis in mouse thymocytes. AB - The p53 tumour suppressor gene is the most widely mutated gene in human tumorigenesis. p53 encodes a transcriptional activator whose targets may include genes that regulate genomic stability, the cellular response to DNA damage, and cell-cycle progression. Introduction of wild-type p53 into cell lines that have lost endogenous p53 function can cause growth arrest or induce a process of cell death known as apoptosis. During normal development, self-reactive thymocytes undergo negative selection by apoptosis, which can also be induced in immature thymocytes by other stimuli, including exposure to glucocorticoids and ionizing radiation. Although normal negative selection involves signalling through the T cell receptor, the induction of apoptosis by other stimuli is poorly understood. We have investigated the requirement for p53 during apoptosis in mouse thymocytes. We report here that immature thymocytes lacking p53 die normally when exposed to compounds that may mimic T-cell receptor engagement and to glucocorticoids but are resistant to the lethal effects of ionizing radiation. These results demonstrate that p53 is required for radiation-induced cell death in the thymus but is not necessary for all forms of apoptosis. PMID- 8479523 TI - Thymocyte apoptosis induced by p53-dependent and independent pathways. AB - Death by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy. Apoptosis can be initiated by various agents and may be a result of expression of the oncosuppressor gene p53 (refs 6-8). Here we study the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca(2+)-dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Our results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage. PMID- 8479524 TI - Solution structure of the POU-specific DNA-binding domain of Oct-1. AB - The transcription factor Oct-1 belongs to a family containing a POU DNA-binding domain. This bipartite domain is composed of a POU-specific domain (POUs) and a POU-homeodomain (POUhd) connected by a flexible linker. The left half of the optimal POU binding site, the octamer ATGCAAAT, is recognized by POUs and the right half by POUhd. We have determined the solution structure of POUs by nuclear magnetic resonance. It consists of four alpha-helices connected by short loops. Helices I and IV are in a parallel coiled-coil arrangement. The folding topology appears to be similar to that of the bacteriophage lambda-repressor and 434 repressor. For the well defined parts of the protein (residues 1-71), the average root-mean square deviation for the backbone atoms is 0.9 A. Based on the observed selective exchange broadening in the (15N,1H)-HMQC (heteronuclear multiple quantum coherence) spectrum of the POUs-DNA complex we conclude that DNA-binding is mediated by helix III. We propose a model for the POU-DNA complex in which both recognition helices from the two subdomains have adjacent positions in the major groove. PMID- 8479525 TI - Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. AB - The tumour-suppressor gene p53 is inactivated in most human malignancies either by missense mutations or by binding to oncogenic proteins. In human soft tissue sarcomas, inactivation apparently results from MDM2 gene amplification. MDM2 is an oncogene product that may function by binding to p53 and inhibiting its ability to activate transcription. Here we show that, when expressed in Saccharomyces cerevisiae, human MDM2 inhibits human p53's ability to stimulate transcription by binding to a region that nearly coincides with the p53 acidic activation domain. The isolated p53 activation domain fused to another DNA binding protein is also inactivated by MDM2, confirming that MDM2 can inhibit p53 function by concealing the activation domain of p53 from the cellular transcription machinery. PMID- 8479526 TI - Yeast DNA repair and recombination proteins Rad1 and Rad10 constitute a single stranded-DNA endonuclease. AB - Damage-specific recognition and incision of DNA during nucleotide excision repair in yeast and mammalian cells requires multiple gene products. Amino-acid sequence homology between several yeast and mammalian genes suggests that the mechanism of nucleotide excision repair is conserved in eukaryotes, but very little is known about its biochemistry. In the yeast Saccharomyces cerevisiae at least 6 genes are needed for this process, including RAD1 and RAD10 (ref. 1). Mutations in the two genes inactivate nucleotide excision repair and result in a reduced efficiency of mitotic recombinational events between repeated sequences. The Rad10 protein has a stable and specific interaction with Rad1 protein and also binds to single-stranded DNA and promotes annealing of homologous single-stranded DNA. The amino-acid sequence of the yeast Rad10 protein is homologous with that of the human excision repair gene ERCC1 (ref. 3). Here we demonstrate that a complex of purified Rad1 and Rad10 proteins specifically degrades single-stranded DNA by an endonucleolytic mechanism. This endonuclease activity is presumably required to remove non-homologous regions of single-stranded DNA during mitotic recombination between repeated sequences as previously suggested, and may also be responsible for the specific incision of damaged DNA during nucleotide excision repair. PMID- 8479527 TI - Problems in Italy. PMID- 8479528 TI - A revived opportunity for fetal research. PMID- 8479529 TI - The dark side of molecular biology. PMID- 8479530 TI - Signal transduction. How receptors turn Ras on. PMID- 8479531 TI - Structural biology. Max in a complex affair. PMID- 8479532 TI - Cerebellar flocculus hypothesis. PMID- 8479533 TI - Study proves Iraq used nerve gas. PMID- 8479534 TI - Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain. AB - The three-dimensional structure of the basic/helix-loop-helix/leucine zipper domain of the transcription factor Max complexed with DNA has been determined by X-ray crystallography at 2.9 A resolution. Max binds as a dimer to its recognition sequence CACGTG by direct contacts between the alpha-helical basic region and the major groove. This symmetric homodimer, a new protein fold, is a parallel, left-handed, four-helix bundle, with each monomer containing two alpha helical segments separated by a loop. The two alpha-helical segments are composed of the basic region plus helix 1 and helix 2 plus the leucine repeat, respectively. As in GCN4, the leucine repeat forms a parallel coiled coil. PMID- 8479535 TI - Glowing report may not avert closure of Dutch primate centre. PMID- 8479536 TI - Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. AB - The proteins Grb2-Sem-5, Shc and Sos have been implicated in the signalling pathway from tyrosine kinase receptors to Ras. Grb2-Sem-5 binds directly to murine Sos1, a Ras exchange factor, through two SH3 domains. Sos is also associated with ligand-activated tyrosine kinase receptors which bind Grb2-Sem-5, and with the Grb2-Sem-5 binding protein, Shc. Ectopic expression of Drosophila Sos stimulates morphological transformation of rodent fibroblasts. These data define a pathway by which tyrosine kinases act through Ras to control cell growth and differentiation. PMID- 8479537 TI - Stolen report alleging discrimination and favouritism in NIH office raises furore. PMID- 8479538 TI - Transgenic N. glauca plants expressing bacterial virulence gene virF are converted into hosts for nopaline strains of A. tumefaciens. AB - Tumours are induced by Agrobacterium tumefaciens on a variety of plants. The virulence determinants of A. tumefaciens reside on a large tumour-inducing (Ti) plasmid. This plasmid carries two regions essential for tumour induction, namely the T region and the Vir region. During infection the T region is transferred to the plant cell, where it becomes stably integrated in one of the host chromosomes as T-DNA. Expression of T-DNA leads to the production of the plant hormones auxin and cytokinin, as well as to the synthesis of specific amino-acid derivatives termed opines. Agrobacterium strains are classified according to the types of opines produced by the tumours they induce. The Vir region contains genes that are expressed in the bacterium and are required for T-DNA transfer to plant cells, and several other genes that affect the efficiency of transfer and the host range. Vir regions from different Ti plasmids may vary slightly in the genes they contain: for instance, the virF gene, which is present in the Vir-region of octopine Ti plasmids, is absent from nopaline Ti plasmids. Mutation of the virF gene leads to a weakened virulence of octopine strains on tomato and Nicotiana glauca (shrub tobacco). Nopaline strains are strongly attenuated in N. glauca compared with octopine strains because of the absence of the virF virulence gene from the Ti plasmid in nopaline strains. The virF gene product may be transferred to and be active in plant cells. Here we isolate transgenic N. glauca plants in which the virF coding sequence is expressed using the cauliflower mosaic virus 35S promoter. The presence of the VirF protein converts the non-host N. glauca into a host for tumour formation by A. tumefaciens nopaline strains and octopine virF mutants. Our results indicate that certain virulence gene products such as the VirF protein may be transferred to plant cells during tumour induction, where they function as mediators of T-DNA transfer. PMID- 8479539 TI - Spatial calcium buffering in saccular hair cells. AB - The potential importance of intracellular calcium-binding proteins in rapid and highly localized Ca2+ signalling is poorly understood. During fast synaptic transmission, which occurs at specialized active zones where Ca2+ diffuses only a few tens of nanometers from channels to neurotransmitter release sites, a cytoplasmic Ca2+ buffer would have to be extremely fast or present in millimolar concentrations to intercept a significant fraction of the calcium ions en route to their targets. Therefore, Ca2+ buffers have been presumed to be unimportant in fast exocytosis and another fast calcium-mediated process, electrical resonance in hair cells. Here I present evidence to the contrary by showing that hair cells in the frog sacculus contain millimolar concentrations of a mobile cytoplasmic calcium buffer that captures Ca2+ within a few microseconds after it enters through presynaptic Ca2+ channels and carries it away from the point of entry. This spatial buffering reduces the presynaptic free Ca2+ by up to 60 per cent and probably restricts the region in which the internal calcium ion concentration exceeds 1 microM to within < 250 nm of each synaptic site. The buffer can thus influence both electrical resonance and synaptic transmission. Calbindin-D28K or a related protein may serve as the mobile calcium buffer, an action similar to its function in transporting Ca2+ across intestinal epithelial cells. PMID- 8479540 TI - The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. AB - Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras GNRP in mammalian cells. PMID- 8479542 TI - Germany revamps system to fund medical research. PMID- 8479541 TI - Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. AB - Many of the actions of receptor tyrosine kinases are mediated by the protein Ras, including the activation of various downstream serine/threonine kinases and the stimulation of growth and differentiation. The human protein Grb2 binds to ligand activated growth factor receptors and downstream effector proteins through its Src-homology (SH) domains SH2 and SH3, respectively, and like its homologue from Caenorhabditis elegans, Sem-5, apparently forms part of a highly conserved pathway by which these receptors can control Ras activity. Here we show that the SH3 domains of Grb2 bind to the carboxy-terminal part of hSos1, the human homologue of the Drosophila guanine-nucleotide-releasing factor for Ras, which is essential for control of Ras activity by epidermal growth factor receptor and sevenless. Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grb2/hSos1 complex couples activated EGF receptor to Ras signalling. PMID- 8479543 TI - Montagnier to assess French AIDS effort. PMID- 8479544 TI - 5-HT3 receptor ligands lack modulatory influence on acetylcholine release in rat entorhinal cortex. AB - The objective of this study was to explore the role of 5-HT3 receptors in modulating potassium (K+)-evoked release of [3H]-acetylcholine ([3H]-ACh) from superfused slices of rat entorhinal cortex previously loaded with [3H]-choline. Rat entorhinal cortices were cross-chopped into 300 microns slices, superfused with oxygenated Krebs buffer containing 2.5 mmol/l Ca2+ and stimulated with two consecutive exposures of 20 mmol/l K+ for 4 min (S1 and S2, respectively). Compounds were added 20 min before S2 stimulation and remained in the superfusion buffer for the duration of the experiment. The S2/S1 ratio was then calculated. Stimulated release of [3H]-ACh was dependent on extracellular Ca2+ and K+ concentration. In Sprague Dawley rats, 2-methyl-5-HT (10(-9)-10(-6) mol/l), in the presence of 1 mumol/l ritanserin or 1 mumol/l ondansetron, had no influence on K(+)-evoked release of [3H]-ACh. In slices prepared from Hooded Lister rats, 2 mumol/l 5-HT but not 2-Me-5-HT significantly (P < 0.05) inhibited K(+)-evoked [3H]-ACh release only 17% in the presence of 1 mumol/l ritanserin. However, 2 mumol/l 2-Me-5-HT plus 1 nmol/l ondansetron had no effect. High performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) was used to monitor endogenous release of ACh in the above conditions to confirm data from the radiolabelled experiments. No significant inhibition or increase in K(+) evoked ACh release was observed with either 5-HT3 receptor agonists or antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479545 TI - Autoradiographic mapping of 5-HT1 receptors in the guinea-pig brain with particular reference to the 5-HT1D receptor sites. AB - The anatomical distribution of 5-HT1 receptors in the guinea-pig brain was studied by means of in vitro quantitative autoradiography using [3H]-5-HT as ligand. The relative presence of the subtypes of the 5-HT1 binding site was investigated by adding selective concentrations of 8-OH-DPAT, (-)21,009, mesulergine and 5-CT. In addition, differentiation of 5-HT1D receptors was achieved by incubation of the tissues with [3H]-5-HT in the presence of 100 nmol/l 8-OH-DPAT together with 100 nmol/l mesulergine. Areas presenting high densities of 5-HT1A receptors included the neocortex (internal layers), hippocampal formation (dentate gyrus, CA1 field), septum and raphe nuclei, while 5-HT1C sites accounted for most of the [3H]-5-HT binding to the choroid plexus. Non 5-HT1A-non 5-HT1C sites (mainly 5-HT1D and, also probably, 5-HT1E receptors) were clearly predominant in the guinea-pig brain. These sites were mainly present in the neocortex (external layers), basal ganglia, hypothalamus and midbrain (substantia nigra, superior colliculus). As previously described, sites with the properties of 5-HT1B receptors could not be clearly identified in the guinea-pig brain. The present results, in addition to providing a detailed map of the 5-HT1 receptors in the guinea-pig brain, indicate that the guinea-pig is a useful laboratory animal for the study of 5-HT1D receptors. PMID- 8479546 TI - Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms. AB - The present study investigated the anorectic activity of d-fenfluramine (d-F) and the relationship with brain levels of unchanged drug and its metabolite d norfenfluramine (d-NF) in marmosets, relating them to neurochemical effects on the serotoninergic system. d-F and d-NF were equally active in reducing food intake (ED50 about 3 mg/kg, p.o.). However, the brain concentrations of the metabolite required to reduce food intake after synthetic d-NF were more than twice those after d-F, indicating that d-NF contributes to but does not completely explain the anorectic effect of d-F. At this dose d-F did not appreciably modify the serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) contents of the brain regions examined, except for a slight enhancement of 5-HIAA in hippocampus. In vitro in brain cortical synaptosomes d-F inhibited [3H]5-HT uptake more potently than d-NF, as in other species. d-F and d-NF showed similar potency in stimulating [3H]5-HT release, in a Ca++ dependent manner. The tritium released by d-F and d-NF appeared to be mainly unmetabolized [3H]5-HT. Like in other species the marmoset too has saturable and specific [3H]d-F binding sites, for which d-NF has lower affinity. d-F and d-NF have low affinities for 5-HT receptor subtypes, except that d-NF has appreciable affinity for 5-HT1C and 5 HT1D receptors. Unlike in rodents but similarly to primates in the striatum the pharmacology of 5-HT receptors seems to correspond to the 5-HT1D subtype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479548 TI - German Society of Pharmacology and Toxicology, 34th spring meeting. Mainz, 16-18 March 1993. Abstracts. PMID- 8479549 TI - Implementing a mandatory drug screening program: pros and cons for the dialysis unit. PMID- 8479550 TI - States tighten grip on limiting physician self-referral, but exceptions for referring to renal care facilities are seen. PMID- 8479547 TI - A target K+ channel for the LP-805-induced hyperpolarization in smooth muscle cells of the rabbit portal vein. AB - The resting membrane potential of smooth muscle cells of the rabbit portal vein was -51.2 mV. LP-805 (8-tert-butyl-6,7-dihydropyrrolo[3,2-e] 5-methylpyrazolo [1,5-a] pyrimidine-3-carbonitrile) hyperpolarized the membrane to -62.3 mV (10 microM) and inhibited the burst spike discharges as measured using the microelectrode method. In dispersed smooth muscle cells, LP-805 (10 microM) generated an outward-current with a maximum amplitude of 68 pA at a holding potential of -40 mV in experiments using the voltage-clamp procedure. The reversal potential of the outward current evoked by LP-805 was -82 mV and this value was close to the equilibrium potential for K+ (-80 mV) in the present ionic conditions, suggesting that LP-805 activated the K+ channel. Generation of both the hyperpolarization and the outward current by LP-805 was inhibited by glibenclamide (> or = 1 microM). Using the cell-attached and cell-free patch clamp (in the presence of GDP) procedures, the maxi-K+ channel current (150 pS) could be recorded in the absence of LP-805; application of LP-805 additionally opened a small conductance K+ channel current (15 pS) without change in the activity of the maxi-K+ channel. The maxi-K+ channel was sensitive to charybdotoxin (0.1 microM) and to intracellular Ca2+ ([Ca2+]i) concentration. The 15 pS channel was insensitive to [Ca2+]i and charybdotoxin, but sensitive to intracellular ATP concentration. Glibenclamide (> 1 microM) inhibited the 15 pS K+ channel activated by LP-805.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479551 TI - Putting data to work. PMID- 8479552 TI - Clinton hopes managed competition will slow runaway health care train. PMID- 8479553 TI - Plenty of questions still remain on Clinton's approach to health care reform. PMID- 8479555 TI - Special travel agencies/summer camps for dialysis and transplant patients. PMID- 8479554 TI - Transplant recipients share expression of music, photography, painting, and writing. PMID- 8479556 TI - Ethics and economics: a tug-of-war for the renal care team? PMID- 8479557 TI - Ethics and economics: a tug-of-war for the renal care team? PMID- 8479559 TI - True reform not likely until '95, but it's coming. PMID- 8479558 TI - TB--will history repeat itself? PMID- 8479560 TI - FOB, FOH, but in 1993, who is a FOM? (Friend of Bill, friend of Hillary, friend of medicine). PMID- 8479562 TI - Defining the important ingredients of a quality laboratory. PMID- 8479561 TI - With education, intervention by family physicians can prevent kidney disease. PMID- 8479563 TI - Looking back: 14 years as a renal social worker. PMID- 8479564 TI - [Dehydration in geriatrics: dry stuff?]. PMID- 8479565 TI - [Report by the Health Council on dialysis and kidney transplantation]. AB - The Health Council of the Netherlands has summarised the developments regarding dialysis and renal transplantation over the period 1985-1990, and estimated the numbers of patients and transplantations for 1995. Currently 21% of the patients are treated with peritoneal dialysis. In 1991 53% of patients undergoing haemodialysis in a specialised centre were dialysed only twice weekly. The figure for the patients being dialysed thrice weekly may rise to 75% in 1995. The number of renal transplantations may rise from 28/million inhabitants in 1991 to 35/million in 1995, which is the figure in the surrounding countries. In that case, the prospective number of dialysis patients in 1995 is 3600; if there is no increase in the number of transplantations, it will be 3790. At this moment 1400 patients are waiting for transplantation; the mean waiting time is > 3 years. PMID- 8479566 TI - [Dehydration in geriatric patients; pathophysiology, diagnosis, therapy and prevention]. PMID- 8479567 TI - [Islet amyloid polypeptide or amylin; breakthrough in the diagnosis and prevention of type II diabetes mellitus?]. PMID- 8479568 TI - [Do foods specially intended for diabetics have any health benefit?]. PMID- 8479569 TI - [Shockwave lithotripsy in the pancreas; the first 16 patients treated in Rotterdam-Dijkzigt]. AB - Sixteen patients, 7 women and 9 men, with a mean age of 42 years and with recurrent attacks of abdominal pain as a result of chronic calcifying pancreatitis, were treated with extracorporeal shock wave lithotripsy (ESWL), after endoscopical removal of one or more stones from the main pancreatic duct had proved impossible. In all patients fragmentation by ESWL of the stone situated farthest distally was attempted, after which the remaining calculi and fragments could be voided spontaneously or could be flushed via a drain placed endoscopically in the main pancreatic duct. In 12 patients (75%) fragmentation of stones was achieved, 11 of them had a dramatic relief of pain immediately after ESWL. In 7 patients (44%) stone clearance was achieved; at follow-up (1-38 months after ESWL) none of these had complaints. Of the 5 patients with stone fragmentation without stone clearance, 2 were operated on because of recurrent symptoms. The only complication seen after ESWL, was an exacerbation of pancreatitis in 1 patient, which could be treated conservatively. If pancreatic stones cannot be removed endoscopically, ESWL appears to be an attractive alternative to an operation. It is important to achieve stone clearance. PMID- 8479570 TI - [Results of 4 years of gallstone lithotripsy]. AB - OBJECTIVE: Determination of the efficacy of extracorporeal shock wave lithotripsy (ESWL) of gallbladder stones and adjuvant treatment with oral bile acids. SETTING: Department of Surgery, University Hospital Dijkzigt, Rotterdam, the Netherlands. DESIGN: Descriptive clinical research. PATIENTS AND METHODS: In 4 years, 133 patients (34 males and 99 females, mean age 49 years (range 24-81)) underwent 299 ESWL sessions, on an outpatient basis except for the first 16. All patients received adjuvant oral bile acid therapy (7-8 mg/kg body weight urso- and chenodeoxycholic acid, starting one day after ESWL). The number of ESWL sessions was 2.5 (mean; range: 1-7) with 2817 shock waves (75-4000), a session duration of 62 min (35-210). 73.7% of the patients (n = 98) required intravenous analgesic sedation. RESULTS: At a mean follow-up of 13.8 months (1-45), 27.6% of the patients were free of stones. At 1 year after the first ESWL session, 51.0% of the patients with a solitary stone and 8.3% of the patients with 2-10 stones were free of stones (p < 0.0001). Of the 43 patients who had become free of stones 6 developed recurrent stones (14.0%). Fifty-seven patients (42.9%) suffered from colic, 9 (6.8%) from obstruction of the common bile duct, including 4 who developed pancreatitis. Two patients had transient haematuria and one acute cholecystitis; 15 (11.3%) suffered from an oral bile acid-related diarrhoea, which could easily be resolved by lowering the dose of chenodeoxycholic acid. 30 patients (22.6%) underwent cholecystectomy. CONCLUSIONS: Our results reconfirm that ESWL is safe and moderately effective in selected patients. Nowadays most patients choose laparoscopic cholecystectomy, which implies that ESWL will be confined to patients with an increased operative risk and to those who refuse surgery. ESWL should be limited to patients with solitary stones. PMID- 8479571 TI - [Dutch psychiatry and the 'Citation Index']. AB - All regular articles in Archives of General Psychiatry, American Journal of Psychiatry, British Journal of Psychiatry and Psychological Medicine from 1988 through 1992 were counted and classified according to the country of the first author. 445 articles (II% of the total number) originated in other countries than the U.S.A., Canada, the United Kingdom and the Commonwealth countries Australia and New Zealand. The Netherlands had the biggest share (48 articles). After correction for population figure the Netherlands were third, after Ireland and Israel. The basis for research in Dutch psychiatry, however, is probably rather narrow, as only few institutes contributed. PMID- 8479572 TI - [How can reinfection by Gardnerella vaginalis be prevented?]. PMID- 8479573 TI - [Surgical correction of urinary incontinence and (or) prolapse symptoms]. PMID- 8479574 TI - [The treatment of erection disorders]. PMID- 8479575 TI - [Aberrant origin of the left coronary artery from the pulmonary artery as cause of ventricular fibrillation in a young woman]. PMID- 8479576 TI - [Thin is not always fashionable]. PMID- 8479577 TI - Women at risk of family violence. AB - Presented here are the basic, core picture and pathognomonic features of spouse (or partner) violence, stripped of obscuring traditional, often male-dominated misinformation. Spouse abuse, like other forms of intentional injury or violence, should no longer be considered tolerable or "normal." It represents a form of psychopathology, corrupting the family emotional setting, provoking human anguish and even death. It often perpetuates itself into the next generation. Assault or murder by an abusive male or lover must be recognized as an all too common, preventable, public health issue. Health care and legal professionals, as well as the public at large, must be informed to recognize the features of this tragic family drama. State laws and welfare agencies have started to accommodate this problem, directing victims to appropriate counseling, support and protection. Reluctant or passive police, attorneys and judges may present considerable frustration to those trying to assist these families. PMID- 8479578 TI - Price comparison between Nebraska rural and urban hospitals for delivery of health services. PMID- 8479579 TI - Toxic strep syndrome. PMID- 8479580 TI - Intrapartum analgesia. PMID- 8479581 TI - Sentimental women need not apply. From the president. PMID- 8479582 TI - Nurses are the ones who are really caring for our patients. PMID- 8479583 TI - ANA position statement on registered nurse utilization of unlicensed assistive personnel. PMID- 8479584 TI - Long-term care for young and old must be part of health care reform, says ANA. PMID- 8479585 TI - [Associative networks, formal thought disorders and schizophrenia. On the experimental psychopathology of speech-dependent thought processes]. AB - Association psychology research in psychiatry dates back to Kraepelin, Aschaffenburg and C.G. Jung. Findings of the 1950s and 60s in this field suggest that semantic memory is organized in the form of a network. New results of experimental psychiatric studies indicate that schizophrenic symptoms, in particular formal thought disorders, are in part the result of an unfocussed activation or disinhibition of such associational network structures: The phenomenon of semantic priming is more pronounced in schizophrenic patients than in normals. Moreover, the phenomenon of indirect semantic priming on short stimulus onset asynchrony can be seen only in schizophrenic patients. The study of spontaneous speech further suggests the activation of structures responsible for the storage and processing of meaning. Increase in semantic priming, similar to that observed in schizophrenia, can further be observed in normal subjects on awakening from REM sleep. The findings are discussed in the framework of recent findings on the neurobiological causes of schizophrenia. They can be related structurally to an involvement of the frontal lobe, and functionally to disturbances of dopaminergic transmission. Methods such as the investigation of priming effects in lexical decision tasks, as well as concepts from the domain of cognitive neuroscience such as neural networks and the spreading activation model of lexical access, can help to bridge the gap between phenomenological psychopathology and neurobiology. PMID- 8479586 TI - [Validation of diagnoses according to psychiatric diagnostic manuals in follow-up studies, exemplified by affective and schizophrenic diseases]. AB - The new international classification schedules ICD-10 and DSM-III-R were developed by committees of experts. These schedules need to be validated. One strategy is to conduct prospective long-term follow-up studies recruiting patients with a broad variety of syndromes diagnosed initially by previous and more recent classification schedules. Studies following this strategy are discussed and a new two-year follow-up study is presented. Several modifying psychosocial and treatment factors and methodological problems impose limitations on the interpretation of those studies with regard to the validity of applied classification schedules. Alternative validation strategies are discussed. PMID- 8479587 TI - [Multiple personality disorder: old concepts presented as new]. AB - The rapid increase in numbers of MPD patients in the Anglo-American literature requires discussion of the diagnostic concept. The classification of MPD as Dissociative Disorders by DSM-III-R and ICD-10 follows the traditional conceptualization of hysteria and hypnosis. In the view of the majority of modern authors child abuse appears as a new etiological issue. This theme highly sensitive is critically discussed against the background of older psychopathological concepts of forgetting. A careful analysis of personality traits and motivation in the individual case help to avoid overuse of the new diagnostic label. PMID- 8479588 TI - [Prognosis of puerperal psychoses: follow-up and outcome after an average of 26 years]. AB - 61 women, who became ill for the first time in their life within 6 weeks after childbirth were investigated after a mean of 25.6 years (minimum 12, maximum 41 years), using various standardised instruments of evaluation. A total of 39 Patient (63.9%) had had a recurrence of illness, the average number of further episodes being 4.8. 31 of the women had had additional pregnancies and deliveries, and 8 of these (25.8%) had suffered another postpartum psychosis. 23.5% of the patients who had reached or passed the climacteric became ill again in close connection with that time (first time after the postpartum psychosis or first time after a relapse-free interval of more than 12 years). 72.1% of the patients were symptom-free at the time of follow-up, only 17 (27.9%) showed persisting alterations (13.1% "adynamic-deficient syndrome", 9.8% "slight asthenic insufficiency syndrome", 4.9% "chronic subdepressive syndrome"). Considering also the findings according to the Global Assessment Scale (GAS) and Disability Assessment Schedule (WHO/DAS) the long-term outcome was found to be favourable in the majority of cases, with regard to the frequency and intensity of disability and persisting alterations. PMID- 8479589 TI - [Effect of therapy variables on suicide of released psychiatric clinic patients. Results of a controlled study]. AB - We studied therapeutic factors influencing the risk of suicide during outpatient treatment. A total of 64 former psychiatric inpatients who had committed suicide within one year after their discharge were compared with the same number of control patients fulfilling the following matching criteria: sex, age, RDC diagnosis, year of discharge and length of observation period. There were no significant differences between the two groups in psycho-social or clinical pre discharge variables including previous suicidal behavior, but the suicide subjects became more frequently suicidal during the post-discharge outpatient treatment. The formal conditions of the treatment were comparable in both groups. However, the control patients were treated by therapists with substantially longer professional experience and they also more frequently received psychopharmacological agents including lithium. PMID- 8479590 TI - [Empirical findings on the personality structure of borderline patients]. AB - In the present study the question of personality structure in borderline patients is studied empirically. The "Diagnostic Interview for Borderlines" of Gunderson and Kolb is used to classify the patients. In an inpatient sample of borderline patients (n = 26) the clinical diagnoses of personality structure according to psychoanalytic criteria are investigated and compared to those of an inpatient sample of patients with neurotic disorders (n = 24). According to the results most of the borderline patients (88%) had received a diagnosis of a schizoid personality structure according to psychoanalytic criteria, in contrast to the neurotic patients. The results are compared to those of studies using descriptive psychiatric criteria. PMID- 8479591 TI - [Are visual and auditory perception modified in psychopathological assessment of expressive markers of psychiatric patients?]. AB - The assessment of nonverbal expression (e.g. facial action, speech, body movements, etc.) are an important aspect of the diagnostic and prognostic process in psychiatric patients. By means of observer rating scales' expression is usually assessed on different observation levels. It appears that visual and auditory perception of expression interfere with one other. In the present study it was demonstrated, that ratings of certain attributes of expression was significantly more inconsistent in schizophrenic than in depressed patients, provided information was simultaneously displayed to both visual and auditory channels of perception. A "disintegration" of the components of expression in schizophrenics may explain why raters get differings impressions of the patient's overall expression. Moreover, the description of expressive behaviors seems to be influenced by diagnostic stereotypes. The development of a more objective method of assessment would therefore be promising. PMID- 8479592 TI - [A case of "delusional growth". On the origin and nosologic classification of somatic dysmorphic disorder]. PMID- 8479593 TI - [Are phase II or phase II antidepressive drug studies still feasible considering currently required inclusion and exclusion criteria?]. AB - The present policy of pharmaceutical companies to aim at perfectionistic, and therefore inflexible protocols for clinical drug-trials renders patient recruitment increasingly difficult or even impossible, and may result in an increasing number of non-completed studies. It appears that many of today's inclusion and exclusion criteria are not sufficiently assessed in terms of their scientific basis and clinical usefulness. Sense and nonsense of these criteria are discussed. The tendency to adhere to streamlined protocols to certify the needs of drug regulators will severely impair the feasibility and validity of antidepressant drug trials in psychiatric in-patients. PMID- 8479594 TI - [Successful hyposensitization treatment of a patient with schizoaffective psychosis and carbamazepine allergy]. AB - For the prevention of relapse in a 25 year old man with schizoaffective psychosis, lithium was prescribed but had to be discontinued because the patient developed psoriasis. Carbamazepine was started but had to be discontinued as the patient developed a generalized substance-induced skin rush. A six-week desensitization procedure with increased oral doses, starting with 1 mg per day, allowed relapse prevention with carbamazepine on a usual dosage. To our knowledge, this is the first report of a successful desensitization of a psychiatric patient with carbamazepine allergy. PMID- 8479595 TI - [Wilhelm Griesinger and the Stuttgart community hospital--experiences with community care. Comments on the contribution by W. Rossler. Wilhelm Griesinger and community care]. PMID- 8479597 TI - Regulation of malate dehydrogenases from neonatal, adolescent, and mature rat brain. AB - Since the malate-aspartate shuttle in brain has been shown to be closely linked to brain energy metabolism and neurotransmitter synthesis, the activity of MDH, one of the enzymes of the malate-aspartate shuttle, was studied in cortical non synaptic mitochondria (mMDH) and cytosol (cMDH) in 1-4 day, 18-20 day and 7-8 week old rats. The mean mMDH activity (nmol/min/mg protein) was 10,517 +/- 734 (mean +/- SEM), 8,882 +/- 241 and 10,323 +/- 561 and cMDH activity was 2,453 +/- 99, 4,673 +/- 152 and 6,821 +/- 205 in 1-4 day, 18-20 day and 7-8 week old rats, respectively. While cMDH activity increased with age (p < 0.0001), mMDH activity showed no change. This study also determined if endogenous compounds, previously shown to alter malate metabolism, affected MDH activities. Lactate inhibited only cMDH activity, by a competitive mechanism. Oxaloacetate inhibited mMDH by partial non-competitive inhibition and cMDH by competitive inhibition. Alpha ketoglutarate competitively inhibited both enzymes; however, the inhibition of mMDH activity was more pronounced than that of cMDH activity. Citrate inhibited mMDH via an uncompetitive mechanism and cMDH via a noncompetitive mechanism. The mechanisms of inhibition of mMDH and cMDH by each of the effectors were the same over the three ages. The results suggest mMDH and cMDH activities show a dissimilar developmental pattern and may be regulated differently by endogenous effectors. The greater sensitivity of mMDH, compared to cMDH, to certain effectors may be related to the dual role of mMDH in the tricarboxylic acid cycle and the malate-aspartate shuttle. PMID- 8479596 TI - Is ammonia a pathogenetic factor in Alzheimer's disease? AB - An attempt was made to review experimental evidence in favor of the idea that ammonia plays a role in dementia of the Alzheimer type (DAT). Hyperammonemia causes biochemical and cellular dysfunctions in the brain, which can be found in brains of DAT patients. The most conspicuous among these findings are astrocytosis, impairment of glucose utilization, and a decreased rate of energy metabolism, and the impairment of neurotransmission, with a net increase in excitability and glutamate release. The derangement of lysosomal processing of proteins is another potential site of ammonia action. This aspect is especially important in view of the growing evidence for the role of the endosomal-lysosomal system in the formation of amyloidogenic fragments from beta-amyloid precursor protein. Ammonia is not considered a primary factor of the disease. However, since hyperammonemia and release of ammonia from the brains of DAT patients is well supported by published observations, ammonia should be taken into account as a factor that contributes to manifestations and the progression of DAT. If elevated ammonia concentrations turn out to be indeed as important in DAT, as is suggested in this review, rational therapeutic avenues can be envisaged that lead to the amelioration of symptoms and progression of the disease. PMID- 8479598 TI - Abundant Gs alpha mRNA in basket cells of the dentate gyrus in adult rat hippocampus. AB - In situ hybridization histochemistry (ISHH) has been used to study the differential distribution and relative abundance of mRNAs encoding a stimulatory alpha subunit of the G-protein (Gs alpha) and glutamic acid decarboxylase (GAD) in the dorsal hippocampus in adult rat brain. The present quantitative study shows that GABAergic neurons containing high levels of GAD mRNA, express considerably more Gs alpha message than excitatory principal neurons, the granule cells of the dentate gyrus and the pyramidal cells of CA1 subfield. A subpopulation of basket cells of the dentate gyrus exhibited a uniquely high level of Gs alpha mRNA, in addition to GAD. These findings may indicate a specific functional role for Gs alpha in these GABAergic neurons in the hippocampus. PMID- 8479599 TI - Nuclear benzodiazepine binding: possible interaction with thyroid hormone receptors. AB - The biochemical and pharmacological properties of nuclear [3H]flunitrazepam in brain tissues were studied. Nuclear [3H]flunitrazepam binding is saturable for both central and peripheral binding sites. Inosine and hypoxanthine displace nuclear [3H]flunitrazepam binding with greater potency than the membrane [3H]flunitrazepam binding. Triiodothyronine (T3) increases the maximum number of binding sites (Bmax) of nuclear [3H]flunitrazepam binding in vitro while thyroxine (T4) does not have any effect. Diazepam reduces the affinity of nuclear 125I-T3 binding in vitro, while the Bmax is not affected significantly. Mild digestion of chromatin, using micrococcal nuclease, reveals that a major portion of nuclear [3H]flunitrazepam binding sites are located on chromatin. These data suggest a functional role for nuclear benzodiazepine binding and a possible modulatory effect of benzodiazepines on T3 binding with its nuclear receptors. PMID- 8479600 TI - Naphthalenesulfonamide derivatives ML9 and W7 inhibit catecholamine secretion in intact and permeabilized chromaffin cells. AB - The role of protein phosphorylation in catecholamine secretion from bovine adrenomedullary chromaffin cells was studied using different protein kinase inhibitors. Naphthalenesulfonamide derivatives as ML9 and ML7, more specific for the myosin light chain kinase, and the calmodulin antagonist W7 inhibited catecholamine secretion 20 and 40% respectively in digitonin-permeabilized chromaffin cells. ML9 also decreased calcium evoked protein phosphorylation of different proteins including tyrosine hydroxylase in permeabilized cells. These naphthalenesulfonamide derivatives showed also an effect in intact cells, ML9 and W7 produced 50% inhibition in catecholamine secretion and 45Ca2+ uptake, however H8 had no effect. The partial [3H]nitrendipine binding displacement of these drugs to adrenomedullary membranes suggests that these sulfonamide derivatives could interact directly with L-type calcium channels in intact cells. The results obtained in permeabilized cells suggest a possible role of protein phosphorylation in the regulation of catecholamine secretion in chromaffin cells. PMID- 8479601 TI - The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance. AB - L-dopa, the major treatment for Parkinson's disease (PD), depletes S-adenosyl-L methionine (SAM). Since SAM causes PD-like symptoms in rodents, the decreased efficacy of chronic L-dopa administered to PD patients may result from a rebound increase in SAM via methionine adenosyl transferase (MAT), which produces SAM from methionine and ATP. This was tested by administering intraperitoneally saline, or L-dopa to mice and assaying for brain MAT activity. As compared to controls, L-dopa (100 mg/kg) treatments of 1 and 2 times per day for 4 days did not significantly increase MAT activity. However, treatments of 3 times per day for 4 and 8 days did significantly increase the activity of MAT by 21.38% and 28.37%, respectively. These results show that short interval, chronic L-dopa treatments significantly increases MAT activity, which increases the production of SAM. SAM may physiologically antagonize the effects of L-dopa and biochemically decrease the concentrations of L-dopa and dopamine. Thus, an increase in MAT may be related to the decreased efficacy of chronic L-dopa therapy in PD. PMID- 8479602 TI - Rat brain microsome fluidity as modified by prenatal ethanol administration. AB - The fluorescence anisotropy (r) of diphenylhexatriene (DPH) and of trimethylamino diphenylhexatriene (TMA-DPH) as a function of temperature (10 degrees to 54 degrees C) was measured in brain microsomes of newborn rats prenatally exposed to ethanol. In this temperature range, the relationship between r and T was linear. The addition of ethanol in vitro to microsomal suspensions influenced the slope of the line of r versus T only when DPH was used as a probe and with high concentrations of the alcohol (> or = 0.3 M). The administration of ethanol (18% of total energy intake) in vivo to pregnant dams affected the slope of the lines of r versus T of the microsomes of pups, either using DPH or TMA-DPH as probes. The slope was also affected in brain microsomes obtained from dams, yet, only with TMA-DPH and in the opposite sense than in pups. We conclude that the effect of prenatal exposure to ethanol depended on metabolic alterations induced by the alcohol and not on its detergent properties for the following reasons: (a) The effects in vitro and in vivo were different and (b) in vitro effects could be obtained only with high concentrations (> or = 0.3 M), whereas in vivo effects were produced by small doses of ethanol. Besides, the effects of the administration of the alcohol in vivo were different in adult and intrauterine life. PMID- 8479603 TI - Actions of a monoclonal antibody Tor 23 on rat brain presynaptic cholinergic processes. AB - Tor 23 is a monoclonal antibody, generated against cholinergic terminals of the Torpedo californica, that has been found to bind to the extracellular surface of cholinergic neurons in a variety of tissues. This study shows that Tor 23 inhibits: 1) high affinity [3H]hemicholinium-3 binding to detergent-solubilized membranes prepared from rat neocortices; 2) high affinity [3H]choline uptake in rat neocortical and striatal P2 preparations; and 3) [3H]acetylcholine synthesis in isolated nerve terminals. Tor 23 does not appear to affect low affinity [3H]choline uptake or [3H]acetylcholine release. These results are consistent with the hypothesis that Tor 23 may bind to nerve terminal high affinity choline transporters in the rat brain. PMID- 8479604 TI - Neurotoxicity of 2,4-dichlorophenoxyacetic butyl ester in chick embryos. AB - Fertilized hens' eggs were externally treated, before starting incubation, with a single dose of 2,4-Dichlorophenoxyacetic butyl ester (2,4-D b.e., 3.1 mg/egg). Chicks at different developmental stages were examined, extending from 10 day embryos to one day after hatching. Previously, we demonstrated that 2,4-D b.e. produces hypomyelination in chicks born from treated eggs. In search of the causes of this hypomyelination, "myelin markers" such as sulphatides, cerebrosides and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity, as well as protein and nucleic acid contents were determined in the embryonic brains. We have shown in the present study that the chemical alterations occurred even before the period of active myelination, since myelin appears in chicken brain stem and cerebrum approximately after 17 days of incubation, and most of the chemical parameters studied are diminished before that time. The DNA content in brain of treated group is increased from the 14th embryonic day (with a transient diminution at 12th day) to the first hatching day, when compared to the control, suggesting a proliferation of glial cells, possibly oligodendrocytes. PMID- 8479605 TI - Colocalization of progestin receptors with serotonin in raphe neurons of macaque. AB - Progesterone stimulates prolactin secretion in estrogen-primed women and monkeys. We hypothesize that this effect is neurally mediated since pituitary lactotropes do not contain progestin receptors (PR). In rodents, progesterone enhances hypothalamic serotonin (5HT) content, and both progesterone and 5HT stimulate prolactin and LH secretion. However, it was not known whether progesterone acts directly on 5HT neurons or through other neurons. Using a double immunocytochemical procedure, we show that 5HT neurons in macaque contain PR and thus are a progestin target system. Midbrain tissue blocks were obtained from two female monkeys and immersion-fixed prior to freezing and sectioning. PR was detected with a monoclonal antibody against human PR (B39) bridged to horseradish peroxidase and developed in diaminobenzidine. PR immunoreactivity appeared as a brown reaction product which localized in the nuclei of individual neurons. 5HT was detected with an antiserum generated against a conjugate of 5HT and BSA bridged to alkaline phosphatase. 5HT immunoreactivity appeared as a blue reaction product in the cytoplasm and axons of the pontine raphe nucleus. Neurons containing both nuclear reaction product for PR and cytoplasmic reaction product for 5HT were observed in both the dorsal and ventral aspects of the midbrain raphe nucleus as well as the raphe magnus. In summary, progesterone can have a direct action on 5HT neuronal function and thereby influence those endocrine and affective systems under serotonergic control. PMID- 8479606 TI - Chronic ethanol increases proopiomelanocortin gene expression in the rat hypothalamus. AB - The effect of chronic ethanol exposure on proopiomelanocortin (POMC) mRNA accumulation, beta-endorphin (beta-EP) levels as well as incorporation of [3H] phenylalanine into beta-EP-related peptides was investigated in the rat hypothalamus. Animals were treated with an ethanol-containing liquid diet for 15 days. Both sucrose pair-fed and ad libitum-fed control groups were included. The levels of immunoreactive beta-EP, as well as the relative proportions of nonacetyl and acetyl forms of beta-EP in the hypothalami of the ethanol-treated rats were not significantly different from those in the sucrose and lab chow fed control rats. Northern blot analysis of total hypothalamic RNA indicated that ethanol-treated rats had higher POMC mRNA levels than sucrose pair-fed and control rats. Quantitation of the in vitro incorporation of [3H]-phenylalanine into POMC, beta-lipotropin and beta-EP by the hypothalamus, using immunoprecipitation and polyacrylamide disc-gel electrophoresis with sodium dodecyl sulfate, revealed that the increased hypothalamic POMC mRNA content was associated with increased incorporation of [3H]-phenylalanine into POMC by the hypothalami of the ethanol-treated rats. It is concluded that chronic ethanol can alter the expression of the POMC gene in the hypothalamus. PMID- 8479607 TI - Effects of naloxone on estrogen-induced changes in hypothalamic gonadotropin releasing hormone pulse generator activity in the rhesus monkey. AB - In the ovariectomized rhesus monkey, estradiol (E2) markedly reduces the frequency of the GnRH pulse generator as monitored by LH pulse frequency and the concurrent changes in hypothalamic electrical activity, an action mimicked by morphine. In addition, the duration of the increments in multiunit electrical activity (MUA volleys) that precede each LH pulse is decreased by estrogen administration, an action also shared by morphine. The role of endogenous opioids in these actions of E2 was investigated in 8 ovariectomized animals restrained in primate chairs. They were fitted with indwelling cardiac catheters and with bilateral arrays of recording electrodes chronically implanted in the mediobasal hypothalamus. Physiological serum E2 levels achieved by subcutaneous implantation of E2-containing Silastic capsules increased MUA volley interval from 50.8 +/- (SEM) 1.6 min in the control period to 81.1 +/- 6.2 min following E2. Mean MUA volley duration decreased from 21.9 +/- 1.0 to 13.0 +/- 0.7 min. The placement of empty Silastic capsules had no effect on MUA volley duration or interval. Naloxone administration (2.5 mg bolus followed by a 1 mg/h infusion lasting 4-8 h) completely (n = 4) or partially (n = 2) blocked the effects of E2 on MUA volley interval in 6 of the 8 monkeys, and was without effect in the remainder. In contrast, however, naloxone had little or no effect on the action of E2 on MUA volley duration, (13.0 +/- 0.7 vs. 14.0 +/- 0.9 min). These findings suggest that the inhibitory action of E2 on GnRH pulse generator frequency, like that of all other gonadal steroids studied to date, may be mediated by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479608 TI - Enhancing effect of intracerebrally infused beta-endorphin antiserum on the secretion of cortisol in foot-shocked sheep. AB - It was found in our earlier experiments that infusion of beta-endorphin (beta End) into the 3rd brain ventricle in sheep elicited a differential effect on the secretion of cortisol under physiological and stress conditions. Under physiological conditions it elevated the level of cortisol in the peripheral blood, while in stressed animals it suppressed it. To obtain further support for the suppressive action of beta-End on cortisol secretion under stress conditions a beta-End antiserum was infused into the 3rd ventricle of the brain in stressed and nonstressed sheep and the concentration of plasma cortisol was measured. Stress was induced by mild electric foot shock. Infusion of the beta-End antiserum during stimulation enhanced the plasma cortisol values, when compared with those obtained during the infusion of rabbit hyperimmune serum containing anti-guinea pig gamma-globulins or saline. Moreover, during the infusion of beta End anti-serum some aggravation of stress symptoms expressed by the increase of restlessness and higher frequency of defecations and urinations was observed. Additional experiments carried out to study the effect of beta-End on prolactin (PRL) secretion showed that this opioid induced a very high secretion of PRL in stressed animals. On the basis of these data and the known suppressive action of PRL on the corticosterone response to stress in the rat, we suggest that the suppressive action of beta-End on cortisol secretion in stressed sheep could be caused by the action of PRL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479609 TI - Neuropeptide Y regulation of LHRH release in the median eminence: immunocytochemical and physiological evidence in hens. AB - It has been suggested that hypothalamic median eminence (ME) might be a control site for luteinizing hormone-releasing hormone (LHRH) release. Thus, stimulatory and/or inhibitory inputs acting at this site might be involved in regulating LHRH release from the ME and, therefore, luteinizing hormone (LH) release from the anterior pituitary. Since a role for neuropeptide Y (NPY) on LH release has been suggested, we have hypothesized that NPY might act in the ME to control preovulatory LHRH release in hens. To examine this possibility we have determined: (a) the immunocytochemical distribution of LHRH and NPY in the ME of the hen, (b) the basal and NPY-stimulated release of LHRH in vitro from the ME of hens undergoing a natural or a premature preovulatory surge of LH, and (c) the tissue content of LHRH and NPY in microdissected MEs, at various times before and during a natural or a premature preovulatory surge of LH. A potential role for NPY on LHRH release in the ME is suggested for the following reasons. (a) There are opportunities for synaptic interactions between NPY and LHRH-containing axons at this site. LHRH-containing cell bodies localized in the anterior hypothalamus/medial preoptic area project to the ME. NPY-containing perikarya, concentrated in the ventromedial aspect of the arcuate nucleus, might contact LHRH processes going to the ME and/or might themselves send axons to the ME, (b) Addition of NPY to the incubation media increases LHRH release from microdissected ME tissue of hens killed at the time of the natural preovulatory surge of LH, but not in hens killed 7 h before the occurrence of this surge. However, the stimulatory effect of NPY on LHRH release can be induced at this latter time when a premature LH surge is elicited. While the natural preovulatory surge of LH occurs 4 h before the second ovulation in a sequence (C2 ovulation), administration of progesterone (P4) 10-14 h before the expected natural C2 ovulation advances the natural LH surge by 7-8 h. Thus, NPY might act as a physiological stimulus of LHRH release at the ME during the preovulatory surge of LH. This is suggested since in vitro basal LHRH release from denervated ME tissue does not change before and during the natural or the premature LH surge. Therefore, preovulatory release of LHRH in vivo might be under a continuous drive from stimulatory inputs to the LHRH neuron and NPY might be one of these stimulating factors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8479610 TI - Effects of rat prolactin on gonadotropin-releasing hormone secretion by the explanted male rat hypothalamus. AB - Chronic hyperprolactinemia in the rat is associated with suppression of plasma gonadotropin concentrations. The reduction of gonadotropins is considered to be due to either an inhibitory effect of prolactin (PRL) on pituitary gonadotropin secretion and/or suppression of hypothalamic gonadotropin-releasing hormone (GnRH) release. In contrast to the in vivo effects of PRL on hypothalamic GnRH release, it has recently been reported that endogenous hypothalamic PRL exerts a tonic stimulatory effect on GnRH release in vitro. The present study was undertaken to further evaluate the role of PRL on GnRH release. To accomplish this, we set up a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release by individually incubated longitudinally halved hypothalami. PRL at the concentrations of 100 and 1,000 nM (2,300 and 23,000 ng/ml) inhibited iGnRH release. This suppressive effect of PRL was apparently specific since growth hormone, a PRL-related molecule, did not have any significant effect on iGnRH release at the concentration of 1,000 nM (21,500 ng/ml) and a PRL antiserum completely suppressed the inhibitory effect of exogenously added PRL. On the other hand, this antiserum had no effect on basal iGnRH release suggesting that hypothalamic PRL does not regulate GnRH release. Based on the observation that PRL exerts a sexually dimorphic effect on plasma gonadotropin levels, we also evaluated the effects of testosterone (T), dihydrotestosterone (DHT), 17 beta-estradiol (E2), and progesterone (P) on PRL inhibited iGnRH release in vitro. T, DHT and E2 did not have any detectable effect on PRL-suppressed iGnRH release whereas P, at the concentration of 0.1 nM (0.03 ng/ml), completely abolished the effect of PRL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479611 TI - Intracellular recordings from neurons of the arcuate nucleus in superfused explants of rat hypothalamus. AB - The membrane properties of arcuate nucleus (ARN) neurons and their connections with extranuclear regions were examined in vitro, using intracellular recordings obtained in superfused explants of rat hypothalamus. Current-clamp analysis revealed that the electroresponsive properties of a large proportion of ARN neurons are influenced by the expression of various forms of low threshold rectification. When the initial membrane potential of a neuron was maintained negative to -70 mV, depolarizing current injection could precipitate an immediate bursting response, due to the activation of a low-threshold spike, or delay firing as a result of transient outward rectification. These properties represent a means by which changes in membrane potential may modulate the responsiveness of ARN neurons to synaptic input. Indeed, electrical stimulation revealed that in addition to efferent projections to the supraoptic nucleus, medial preoptic area, or neurointermediate pituitary, subgroups of ARN neurons may receive a reciprocal, or collateral innervation from each of these areas. This functional diversity of intrinsic and synaptic mechanisms provides ARN neurons with a high capacity for the complex local processing of afferent information. PMID- 8479612 TI - Characterization of cysteamine induction of the 22K prolactin variant in the rat pituitary. AB - Glandular kallikrein (GK) is an estrogen-induced and dopamine-repressed lactotroph protease postulated to play a role in the processing of prolactin (PRL) to novel hormonal forms. Recent studies have shown that GK can process PRL in vitro from a 25K form to a 22K form in the presence of thiols--which appear to transform PRL into conformations (folding states) that are GK substrates. We and others have reported 22K PRL variants in the rat pituitary which can be increased by the administration of cysteamine (CSH), a biological thiol known to alter PRL conformation in vitro and in vivo. The present study further characterized CSH induction of the 22K PRL variant. Estrogen-primed rats were used in dose-response and time-course studies with CSH. CSH effects on 22K PRL levels were studied by Western blot analysis of reduced pituitary extracts (disulfides reduced with dithiothreitol before electrophoresis). Changes in PRL conformation were studied by Western blot analysis of nonreduced samples (thiols and disulfides trapped with iodoacetamide). CSH increased 22K PRL in a dose-dependent manner that was well correlated with the dose-response curve for changes in PRL conformation. CSH at 300 mg/kg produced 10- to 15-fold increases in pituitary levels of 22K PRL. In the time course study, 22K PRL levels peaked within 2 h, plateaued between 2 and 16 h, and approached control levels by 24 h after CSH dosing. CSH-elicited changes in PRL conformation peaked within 1 h, plateaued between 2 and 8 h, and reached control levels within 16 h of CSH dosing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479613 TI - Epidermal growth factor stimulates thyrotropin secretion in the rat. AB - The present work studied the effects of epidermal growth factor (EGF) on the release of thyrotropin (TSH) and prolactin (PRL) from perifused pituitary glands of 200-gram male Wistar rats. Each pituitary gland, cut into halves, was placed in a chamber of a perifusion system connected to a peristaltic pump which conveyed the perifusion medium (Medium 199, pH 7.3, Gibco, USA) from a reservoir to a chamber at a flow rate of 100 microliters/min. Each tightly closed chamber contained one pituitary gland and 600 microliters medium and it was placed in a water bath at 37 degrees C throughout the experiment. One milliliter samples of effluent were collected every 10 min for 60 min to obtain baseline values of TSH and PRL. Thereafter, TSH-releasing hormone (TRH) 10(-8) M or EGF (10(-11), 10( 10), 10(-9) or 10(-8) M) were added to individual chambers and the 10-min sampling of effluent continued for 60 min. EGF 10(-11) M elicited no TSH response, but 10(-10) and 10(-9) M doses induced significant increases in TSH secretion (p < 0.01) with a peak at 10 min after addition of EGF. In another experiment, EGF 10(-8) M or TRH 10(-8) M significantly elevated TSH secretion (p < 0.01). However, TRH, but not EGF, stimulated PRL secretion (p < 0.01). In the in vivo studies, the intravenous administration of EGF 10(-5) M or TRH 10(-5) M both induced significant elevation of TSH release at 10 min after the injection (p < 0.02 for EGF and p < 0.01 for TRH).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479614 TI - Colocalization of corticotropin-releasing factor and vasopressin in the paraventricular nucleus of the human hypothalamus. AB - The anatomical relationship between corticotropin-releasing factor (CRF) containing cells and arginine vasopressin (AVP)-containing cells in the human hypothalamus was investigated by immunocytochemistry. In the paraventricular nucleus of the hypothalamus (PVH), CRF-like immunoreactivity (CRF-LI) was present exclusively in parvocellular cells, while AVP-like immunoreactivity (AVP-LI) was present in both parvocellular and magnocellular cells. No CRF-immunoreactive neurons were observed in the supraoptic nucleus. All CRF-immunoreactive parvocellular cells in the PVH were also AVP immunoreactive. We confirmed the presence of AVP in the CRF-immunoreactive cells by using two kinds of anti-AVP antisera, one of which recognized the side chain of AVP while the other recognized the ring structure of AVP. Colocalization of CRF-LI and AVP-LI was observed not only in the same perikarya but also in the same nerve fibers of parvocellular cells. The present results raise the possibility that AVP and CRF may be secreted together into the human portal circulation. PMID- 8479615 TI - Central administration of bombesin blocks the estrogen-induced afternoon prolactin surge. AB - The effect of central administration of bombesin (BB), a neuropeptide originally isolated from the skin of frogs, on the estrogen-induced afternoon prolactin (PRL) surge was studied. Two doses of BB, 0.15 and 0.75 micrograms/rat, were injected into the lateral cerebroventricle of estrogen-primed ovariectomized rats at 12.00 h through preimplanted cannulae. Serial blood samples were obtained through preimplanted intra-atrial catheters during the whole afternoon hours. The small dose of BB delayed the afternoon PRL surge for an hour, but did not prevent it from occurring. The large dose of BB, however, blocked the surge completely. When the same effective dose of BB was co-administered with a BB antagonist, [Leu13-psi(CH2NH) Leu14]-BB (L psi L-BB), it no longer inhibited the PRL surge. The afternoon PRL surge was also reinstated in BB-treated rats by giving a single injection of sulpiride (1 microgram/rat, i.v.), a dopamine antagonist, at 14.00 h in the same afternoon. These results suggest that BB, by acting through specific BB receptors, can inhibit the PRL surge possibly through activating the dopaminergic systems. PMID- 8479616 TI - Effects of intracerebroventricular and intrahypothalamic cocaine administration on adrenocortical secretion. AB - Cocaine (COC) has been described as exerting potent stimulatory effects on the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study, we investigated the acute and chronic effects of intracerebroventricular and intrahypothalamic injections of COC in rats. Twenty minutes following intracerebroventricular injection of COC (1-100 micrograms), dose-dependent increases in plasma corticosterone (CS) were observed, although the highest dose tested (100 micrograms) evoked a significantly smaller response than that following 50 micrograms. Prior stressing of the animals resulted in elevated plasma CS levels (315 +/- 16 ng/ml) and significantly decreased plasma CS concentrations following 50 micrograms COC (87.8 +/- 3.2%). Injections above the hypothalamic paraventricular nucleus (PVN), the site of corticotropin-releasing factor-secreting neurons which regulate HPA activity, required relatively higher doses of COC in order to elicit increases in plasma CS; injections of 0.5 microgram had no effect, 1 microgram resulted in an increase to 168 +/- 68 ng/ml (p < 0.005), and 2.5 micrograms produced an increase to 146 +/- 29 ng/ml (p < 0.025). Post-PVN injections of COC, behind the posterior margin of the PVN in the vicinity of the ventral noradrenergic ascending bundle, also required a high dose (2.5 micrograms) in order to elicit a plasma CS response (208 +/- 19 ng/ml; p < 0.005), with no significant response seen following 0.5 microgram COC. No effects of specific neurotoxic lesions of the catecholaminergic or serotonergic innervation of the hypothalamus were observed upon adrenocortical responses to COC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479617 TI - Influence of in vivo reproductive endocrine state on growth hormone-releasing factor stimulated adenylate cyclase activity in anterior pituitary fragments. AB - The growth hormone releasing factor (GRF) stimulated adenylate cyclase activity was evaluated in membrane fractions of anterior pituitary glands from male and female rats and in gonadectomized rats following in vivo gonadal steroid treatments. The baseline adenylate cyclase activity was lower in random estrous cycle female rats as compared with males. When estrous cycle phases were evaluated, diestrus 1 females had a lower basal activity as compared with males, while proestrus females were similar to males. The maximal stimulation of adenylate cyclase activity by GRF (i.e. Vmax) was lower in random estrous cycle female rats than in males. This lower Vmax, relative to males, was more pronounced in diestrus 1 than in proestrus females. There was little difference in the ED50 for GRF-stimulated adenylate cyclase activity among these groups. The adenylate cyclase activity was altered 1 week after gonadectomy or 1 week after gonadectomy plus simultaneous in vivo gonadal steroid treatment. The expression of data as a function of whole tissue (content) or as a function of protein (concentration) influenced magnitude and direction of these treatment effects. This may reflect the proliferation of nonsomatotroph cell populations and altered protein synthetic activity following reproductive endocrine manipulations. When expressed as a whole tissue content, the baseline adenylate cyclase activity was unchanged after gonadectomy when compared to same-sex, gonadal-intact cohorts. However, an increase in the Vmax for GRF-stimulated adenylate cyclase activity was found in gonadectomized rats relative to sham-operated, gonadal-intact cohorts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479618 TI - Endocrine features of glucocorticoid endangerment in hippocampal astrocytes. AB - Metabolic insults, such as ischemia or hypoglycemia, typically cause severe neuronal injury in the hippocampus and this cell vulnerability can be exacerbated by glucocorticoid (GC) exposure. This endangerment can also be demonstrated in vitro in both neurons and astrocytes. Direct GC effects on cell physiology thus appear to play a role, but the actual mechanism remains unclear. In order to clarify whether GCs act as damaging agents via a 'classical' steroid route, we examined the temporal features and steroid-specificity of this synergy in hippocampal astrocyte cultures derived from E18 fetal rats. A 24-hour pretreatment with corticosterone (CORT), the principal GC in the rat, enhanced both hypoxic and hypoglycemic cell damage, as measured by lactate dehydrogenase assay. This damaging effect was abolished when CORT exposure was reduced to 8 or 4 h prior to the hypoglycemic or hypoxic treatment, respectively. A 24-hour exposure to several nonGC steroids also failed to enhance hypoxic cell damage. The damaging effect of CORT was attenuated if steroid exposure occurred during the hypoglycemic insult and was absent in both hypoxic and hypoglycemic paradigms if CORT exposure was limited to the recovery period. These results suggest that GCs aggravate metabolic astrocyte injury via classical hormonal effects that are steroid-specific, receptor-mediated, and emerge slowly after prolonged steroid exposure. PMID- 8479619 TI - Apoptosis in the anterior pituitary gland of the rat: studies with estrogen and bromocriptine. AB - Apoptosis was investigated by electron and light microscopy in the anterior pituitary gland of the male Fischer rat in which hyperplasia of prolactin secreting cells had been induced by estrogen implanted subcutaneously for 6 weeks. Counts by light microscopy of apoptotic cells and cells containing phagocytosed apoptotic bodies increased during a period of 44 h after estrogen withdrawal. Necrosis was present but was not prominent. Administration of bromocriptine after estrogen withdrawal increased apoptotic counts to nearly double those in the absence of bromocriptine. Bromocriptine caused some increase in necrosis. Apoptosis occurred in prolactin-secreting cells identified by immunostaining and in other cells. Phagocytosed apoptotic bodies were seen in folliculo-stellate and not in other cells. It is concluded that apoptosis occurs in the anterior pituitary gland and is induced by bromocriptine. Phagocytosis of apoptotic bodies is a function of the folliculo-stellate cells. PMID- 8479620 TI - On vocal cord dysfunction. PMID- 8479621 TI - More poisonous snakes. PMID- 8479623 TI - Geneva Convention. PMID- 8479622 TI - Emergency transport. PMID- 8479624 TI - 1992 Federal Nursing Service Award recipient. An introduction to monoclonal antibody concepts for the oncology nurse. AB - Over the past 16 years, there has been an explosion of knowledge in the field of monoclonal antibody technology. There is an enormous potential for the use of monoclonal antibodies in the diagnosis and treatment of malignancies, and many clinical trials are under way. This paper serves as an introduction to monoclonal antibody concepts for the oncology nurse. Antibody/antigen principles, production of monoclonal antibodies, common side effects of use, and nursing implications are discussed. Results of a recent clinical trial and a patient case study are used to illustrate the application of radiolabeled monoclonal antibodies as a cancer diagnostic technique. PMID- 8479625 TI - 1992 Mary J. Nielubowicz Award recipient. Nursing organizational restructure: choosing to change. AB - Major organizational change frequently results in fear, anxiety, and resistance. Change is often initiated in response to a perceived threat. However, intentional changes to historical patterns of nursing care delivery are now more prevalent, in the absence of crisis, as leaders anticipate new challenges and fulfill today's nurses' need for high-level professional satisfaction. This essay describes factors which inspired nursing organizational restructure at a naval hospital. The specific modifications made and strategies for managing them are reviewed in the context of using planned change principles and risk-taking behavior to achieve organizational growth. PMID- 8479626 TI - 1992 New York-Tidewater chapters History of Military Medicine Essay Award recipient. James Claude Kimbrough: the father of modern U.S. Army urology. PMID- 8479627 TI - Wartime military service and utilization of VA health care services. AB - This study sought to examine predisposing, enabling, and illness characteristics associated with use of Department of Veterans Affairs (VA) health care services. In view of VA's unique mission to care for war veterans, special attention was given to features of wartime military service as predisposing factors for VA health care use. Data from a 1987 national survey of veterans were used to compare VA users and non-users. Logistic regression analysis was used to identify specific variables independently associated with VA health service use. Among current VA health service users, 55% served in combat and 71% in a war zone. Multivariate analysis showed that high illness level, service-connected disability status, and lack of health insurance are the strongest predictors of VA service use. Significant associations were also found between military service during a wartime era, in a war zone, and in combat, and VA health service utilization. Although no differences were noted in VA health service use between veterans of different wartime eras, it was notable that among Korean War-era veterans alone, war zone and combat exposure were not associated with increased VA health service use, perhaps reflecting the more limited public attention that has been paid to veterans of that war. Veterans with war-related military experience show a distinct affinity for VA services. PMID- 8479628 TI - The military health care provider in litigation: an overview. AB - Nowhere is the importance of readiness more critical than in the context of the health care provider preparing for an appearance in court. Accordingly, it is necessary to maintain a general working knowledge of both the general principles associated with the rendering of health care services in the military and the basic tactics that lawyers may employ toward health care providers during litigation. PMID- 8479629 TI - Electromagnetic pulse (EMP), Part I: Effects on field medical equipment. AB - The electromagnetic pulse (EMP) from a high-altitude nuclear detonation has the potential to cover an area as large as the continental United States with damaging levels of EMP radiation. In this study, two of seven items of medical equipment were damaged by an EMP simulator. Computer circuit analysis of 17 different items showed that 11 of the 17 items would be damaged by current surges on the power cords, while two would be damaged by current surges on external leads. This research showed that a field commander can expect approximately 65% of his electronic medical equipment to be damaged by a single nuclear detonation as far as 2,200 km away. PMID- 8479630 TI - The future of post-residency fellowship education. AB - Post-residency fellowship education has traditionally been a transitionary phase toward a possible career involving medical research and teaching. The increasing sophistication required for performing medical research, the emphasis on molecular medicine, significant overcrowding in specialty disciplines, high student indebtedness, declining availability of government research grant funding, and the rise or academic-corporate joint ventures facilitating technology transfer to the private sector are causing changes in the traditional approach to and content of fellowship programs. In light of the overall recent economic downturn with the consequent contraction in research budgeting, fewer fellows will probably be trained in the near future. Alternatives in fellowship programming and support are explored. PMID- 8479631 TI - A multifocal comparison of health status and physical readiness test results of Navy personnel. AB - Many health risk factors are behaviorally related and therefore subject to modification. This study compared health risk appraisal (HRA) age, chronological age, identified risk factors, physiological measures, and demographic variables with Physical Readiness Test results of 100 active duty Navy personnel. Cholesterol levels were 200 mg/dl or greater in 42% of the subjects, with 32% having total:high-density lipoprotein cholesterol ratios of 5.0 or above. Additionally, HRA ages were significantly higher than chronological ages (p < or = .05). This study presents methods for (1) identifying needs for health teaching and/or counseling, and (2) increasing individual awareness of health risk factors and the effects of lifestyle on health risk. PMID- 8479632 TI - Handcuff neuropathy among U.S. prisoners of war from Operation Desert Storm. AB - Handcuff neuropathy was the most common neurologic problem acquired by U.S. prisoners of war during Operation Desert Storm. Neurologic deficits were exclusively sensory in all those affected and began to resolve shortly after their release from captivity. Some individuals expressed concern that these injuries could be career-threatening. One of those repeatedly restrained felt that he had discovered measures that could be undertaken to lessen the likelihood of developing neuropathy. PMID- 8479633 TI - A survey of Army medical department reserve personnel mobilized in support of Operation Desert Storm. AB - Surveys from 3,930 Army medical reservists mobilized in support of the Health Services Command mission during Operation Desert Shield/Storm were collected as units were demobilized from April to June, 1991. A survey questionnaire addressed questions related to factors associated with mobilization and intentions to remain in or leave reserve service after demobilization. Results were grouped according to rank, years of service, occupational specialty, and reserve category. Survey items used 6-point Likert scales to rate 38 items. Stepwise multiple regression models were developed to predict criterion items. PMID- 8479634 TI - The amateur Radio Emergency Service (ARES) and the National Disaster Medical System (NDMS). AB - The rescue, treatment, and evacuation of thousands of patients from a natural disaster or armed conflict that is coordinated by the National Disaster Medical System must be performed in accordance to health care standards recognized in this country. Without an effective communication system, morbidity and mortality will needlessly rise. A medical communication protocol that addresses this problem is proposed. PMID- 8479635 TI - Accuracy of self-reported health histories: a study. AB - Many military health care providers (including most dental providers) depend on self-reported health questionnaires for critical information about their patients' medical history. These questionnaires demand high standards of patient self-awareness and integrity, and their importance justifies checking their accuracy. The authors checked the accuracy of 155 self-reported health histories by comparing them with histories documented in medical records. Although we found some discrepancies, over 95% of our sample showed reasonable agreement between self-reported medical histories and documented medical histories. PMID- 8479636 TI - A comparison of the visual field restrictions with the M17 series protective mask and the MCU-2/P chemical-biological mask. AB - The U.S. Air Force and U.S. Navy recently adopted the MCU-2/P Chemical-Biological Mask to replace the M17 series of protective masks. Visual field plots were generated on a patient wearing each of these respirators. Although both resulted in a decrease of the visual fields, the magnitude of restrictions was far less with the MCU-2/P Chemical-Biological Mask. PMID- 8479637 TI - Scrub typhus in Korea: importance of early clinical diagnosis in this newly recognized endemic area. AB - Scrub typhus became a well recognized infectious disease threat to military operations in the Pacific Theater during World War II. Early diagnosis and treatment with tetracycline or chloramphenicol dramatically reduces the mortality and morbidity of this disease. Korea is a newly recognized scrub typhus endemic country. We report our experience with 189 scrub typhus patients seen at a civilian outpatient clinic in Chinhae, Republic of Korea, from 1985 through 1990, and verify the accuracy of clinical diagnosis by serologic tests. PMID- 8479638 TI - CHAMPUS recapture in the treatment of ear infections. AB - Ear infections, commonly referred to as otitis media, are one of the most commonly occurring problems of childhood. The "hit and miss" treatment of this disorder can result in parental frustration and early referral for surgical treatment. The application of managed care principles require that a standard approach to care be employed for the treatment of this condition. It should be high-quality, low-cost, and accessible to the patient population. The use of group appointments for common medical problems was first recommended by the military-commissioned PRISM III report of the early 1980s. It was felt that this technique could increase access and improve quality of care. A modification of this concept was tested that allowed the advantages of group parent teaching and medical history intake while preserving the individualized approach to care for a larger number of patients. This method was found to increase the productivity of the clinic by over 100%, while reducing the referral of patients outside the AF clinic to less than 1%. PMID- 8479639 TI - The military gynecologist in low-intensity conflict environment. AB - U.S. military medical personnel have been assigned to Honduras since August 1983. While reserve components have 2-week assignments and Air Force medics receive 3 month assignments, U.S. Army medical personnel are assigned for 6-month tours. Duties include rendering medical care and air evacuation capability to all U.S. Forces in the Central American area of operations, conducting medical civic action programs termed MEDRETES, and assisting the host government in developing and conducting a health care system for indigent rural Hondurans. Gynecological care to women soldiers assigned to this low-intensity conflict environment and gynecological surgery capability for indigent Hondurans has been one important aspect of the military medical presence. PMID- 8479640 TI - Post-extubation non-cardiogenic pulmonary edema. AB - Non-cardiogenic pulmonary edema (NCPE) is a rare entity manifested by pulmonary edema with normal pulmonary arterial pressures. NCPE has been described in children and recently reported in adults. Onset is rapid and late recognition or inappropriate treatment may lead to a fatal outcome. Most adult cases have been attributed to laryngospasm and generation of a large negative intrathoracic pressure causing transcapillary filtration. The majority of reported adult cases were at risk for Upper Airway Obstruction (UAO). This report describes three young, active duty men who developed this entity following routine uncomplicated surgical procedures. Intubations were uncomplicated and fluid management appropriate. No patient had risk factors for UAO. Early extubation with respiratory attempts against a closed glottis may be etiology for this complication. PMID- 8479641 TI - Computed tomography-guided needle localization of suspicious breast lesions. AB - Non-palpable breast lesions, suspicious for carcinoma, are usually localized prior to biopsy using standard mammographic techniques. We report two patients in whom computed tomography was used to localize suspicious non-palpable breast lesions that could not be readily localized using standard mammographic techniques. PMID- 8479642 TI - Recurrent coumadin-induced soft tissue necrosis resulting in mastectomy. AB - A 58-year-old woman developed Coumadin-induced necrosis of the left breast, resulting in a mastectomy. This patient had experienced an earlier episode of coumadin-induced necrosis that resolved spontaneously. The etiology of this rare complication is unknown. The literature has suggested that patients can be restarted on Coumadin without difficulty. This case and others in the literature suggest that this may not be true. Patients requiring long-term anticoagulation should be considered for other treatment modalities if they develop Coumadin induced skin necrosis. PMID- 8479643 TI - [Hematomas of the abdominal rectus muscle]. AB - The authors report their experience in relation to a series of 12 cases of hematoma of the rectus abdominis (ER) observed over the course of 13 years at the 2nd Division of General Surgery at Vicenza Hospital: 7 were spontaneous, 2 post traumatic, 1 occurred during anti-coagulant treatment, 1 in a patient with altered coagulation levels due to liver cirrhosis, and 1 was post-operative. Clinical symptoms were sub-acute in 8 cases and were characterised by abdominal pain in all cases, the appearance of an abdominal mass in 4 cases and by ecchymosis in 3 cases. Symptoms were acute in 4 cases with signs of impaired general conditions and anemia. Echography made a decisive contribution to the diagnosis in this pathology and, based on the author's experience, when it was used it prevented the use of surgery. Computerised axial tomography, although it contributed a few precise findings to the diagnosis of ER, was rarely useful. Eight patients were operated: 2 due to collapse and anemia, 4 due to failure to identify the disease, 1 due to persistence of the parietal mass, and 1 due to infection of the hematoma. In the 4 cases which were not operated, the course of the disease was more favourable. The sole death was an elderly cardiopathic patient due to postoperative complications following general surgery. The most suitable therapeutic approach, in those cases where an accurate diagnosis of ER has been made, is to refrain from any form of treatment and to monitor symptoms until they resolve, which will occur spontaneously after 20-30 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479644 TI - [Multiple synchronous colorectal carcinomas]. AB - The authors studied 118 patients with colon cancer (65 males and 53 female) admitted and operated at the Surgical Department of the Casalpusterlengo Hospital (Milan, Italy); over a period of 5 years (1986-1990). All patients were submitted to a pre-op. work-up with Barium enema, colonoscopy, abdominal ultrasound exam, and PAP-test and mammogram for females patients. We found 7 cases (5.9%) of multiple synchronous colon cancer (in 4 patients 2 cancers and in 3 patients 3 cancers). We also found extracolonic malignancy in the same patients (1 synchronous and 2 metachronous). New criteria are proposed to distinguish multiple colon cancers from multifocal colon cancers. It may be concluded that every patient with colo-rectal cancer requires a complete pre-op. examination of the colon and some tests to rule out other extracolonic malignancy. PMID- 8479645 TI - [Morbidity and mortality after elective Billroth II gastric resection in duodenal ulcer. Authors' experience]. AB - A retrospective study was carried out those patients who underwent elective Billroth II gastric resection for pyloric or duodenal ulcer at the Surgical Division of the Scientific Institute of Gastroenterology of Castellana Grotte between 1974 and 1989. The aim of the study was to asses the incidence of postoperative morbidity and mortality. A total of 526 patients were included in the study (mean age 49 years +/- 12 years; 451 males (86%) and 75 females (14%). Morbidity was 20.7% and mortality 1.5%. These findings are in line with those reported in the literature and confirm that gastric resection for duodenal ulcer, even when performed electively, has a far from negligible morbidity and mortality rate. It is well known that, in comparison to more conservative operations such as vagotomy, gastric resection for peptic ulcer presents a high rate of postoperative morbidity and mortality, but a lower incidence of ulcerous recidivation. Unless there are valid preoperative criteria on which to base the choice of one or other techniques, the surgeon will usually choose the method with which the is most familiar. until studies have been carried out to identify the risk factors leading to postoperative morbidity and mortality, the authors suggest that gastric resection is reserved for those patients presenting a low operative risk. PMID- 8479646 TI - [Trends in the incidence of acute appendicitis in Italy during the past 30 years]. AB - The incidence and mortality rate of acute appendicitis for the years 1955 and 1987 were calculated on the basis of data used by ISTAT. In 1955 the incidence was 5.7 per 1000 whereas in 1987 this had fallen to 3.7 per 1000. In both years examined there was a prevalence of females (in 1987 females accounted for 4.3 per 1000 in comparison to 3 per 1000 recorded for for males). In 1987 the lowest incidence was recorded in the over 60 years olds, whereas the highest incidence was in males between 1 and 14 years old (7.57 per 1000) and females between 15 and 24 years old (12.17 per 1000). Mortality diminished from 0.42% in 1955 to 0.05% in 1987. The highest rate of mortality was recorded in those patients over 60 years old (1.5%). PMID- 8479647 TI - [Intra-operative irrigation during colonic resection and anastomosis in colonic obstruction]. AB - The faecal loading associated with colonic obstruction is a fundamental deterrent to constructing a primary distal colonic anastomosis. The authors describe their preliminary experience of intraoperative colonic irrigation in the management of left sided large bowel emergencies. Five patients were operated using this technique (4 cancer obstruction and one sigma volvulus). They show good results performing primary anastomosis after emergency distal resection combined with complete colonic cleansing. PMID- 8479648 TI - [Symmetry, ptosis and a new infra-mammary border in the reconstruction of the breast with a tissue expander]. AB - The aim of this procedure is to obtain a permanent prosthesis (after mastectomy and the insertion of a tissue expander) that is similar to the contralateral breast in volume, morphology and inframammary border. The technique involves aspiration of the tissue expander fluid until the desired volume is obtained and the measurement of the fluid which indicates the volume of the prosthesis to be inserted. Given the satisfactory results obtained, the intention is to continue adopting this procedure. PMID- 8479649 TI - [Heterologous lyophilized collagen in the secondary healing of pilonidal fistulae]. AB - The authors evaluate heterologous lyophilized collagen efficacy and tolerability in second intention healing of pilonidal sinus fistulae. This therapeutical approach seems to be characterized by a lower relapse incidence. The use of heterologous lyophilized collagen relevantly reduces the prolonged healing time required by such method. PMID- 8479650 TI - [Hypocobaltemia in chronic obstructive arteriopathy. Physiopathologic and therapeutic importance]. AB - The role of some so-called primary and secondary (or oligo-elements) elements in the physiopathology of the cardiocirculatory system has been well known from a number of years and they have been regularly included in the treatment protocols. Some, including K, Ca, Mg and Zn, are extremely well known and widely used in clinical practice. Recently, however, a growing number of studies have focused on the biological importance of other oligo-elements in the pathogenetic mechanisms of atherogenesis and its clinical manifestations. This study aimed to verify the exact role of free cobalt in the physiopathology of the chronic obstructive arterial diseases (COAD). A total of 80 patients affected by 2nd stage COAD were examined and the levels of some oligo-elements, including Co, were assayed. Constantly low levels were found (85% of cases) in relation to other oligo elements studied (Cu, Zn, Mg, Ca). This findings is particularly interesting since it confirms the biochemical hypothesis of atherosclerosis according to which parietal damage plays a central role in the pathogenetic mechanism. Some enzymatic deficiencies, which lead to changes in membrane stability at the level of the endothelial cells, are closely related to the presence of tissutal and humoral peroxidation products. These peroxides (lipid peroxides), which are formed following the interaction of fatty acids with oxygen free radicals, have been identified by a number of studies as being responsible for endothelial damage. Several authors have shown that lipid peroxidation is involved in the atherogenic process through several mechanisms entailing monocytic activity and reduced prostacyclin (PG2) synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479651 TI - [ Tissue and blood CEA levels in stomach cancer]. AB - The assays of serum CEA is a useful prognostic marker in patients with stomach cancer. In this study pre-operative serum CEA and tissue CEA in tumour or biopsy were assayed in a group of patients with gastric carcinoma in order to assess their prognostic roles. Based on an analysis of the results the authors affirm that high serum CEA levels in patients with advanced stages of stomach cancer indicate a fatal prognosis, and likewise the finding of tissue CEA in loco regional lymph nodes at the same concentration as that in the primary tumour is also the sign of a severe prognosis. PMID- 8479653 TI - [Abdominal desmoid tumor]. AB - Two cases of desmoid tumor of the abdominal wall are reported, together with some considerations and a review of the literature; desmoid tumor is an unusual neoplasm which affects women in prevalence. This is an histologically benign neoplasm with no metastatic capacity; however it is highly invasive in the site where it arose, so its treatment can become very difficult. The treatment is by surgical excision that must be as wide as possible, in order to obviate the great incidence of recurrence. The role of radiotherapy, hormone and chemotherapy has not been completely assessed so far. PMID- 8479652 TI - [Primary malignant melanoma of the esophagus. Report of 3 cases and review of the literature]. AB - Primary malignant melanoma of the esophagus is an extremely rare tumour with a fatal prognosis. Only 122 cases have been reported to date in the literature, of which 105 are undoubtedly primary. This study presents three new cases which were surgically treated: two cases underwent subtotal esophageal resection and intrathoracic esophagogastroplasty, and one case underwent total esophageal resection and cervical esophagogastroplasty. The histogenesis, role of immunochemical markers and the therapeutic problems related to malignant esophageal melanoma are discussed in the light of a new review of the literature. PMID- 8479654 TI - [Surgical treatment of aneurysms of the popliteal artery]. AB - The authors report their experience of two cases of popliteal artery aneurysm. Both patients were treated with aneurysm resection and inverse saphenous vein bypass. Early surgical intervention is the only effective therapeutic tool to avoid serious complications of this pathology. PMID- 8479656 TI - [Role of surgery for non-Hodgkin lymphoma of the gastrointestinal tract]. AB - From January 1974 to December 1990, 619 patients were submitted to surgical treatment for gastrointestinal carcinoma: 10 cases (1.61%) of non-Hodgkin's lymphomas were observed (4 of the stomach, 3 of the small intestine, 1 of the colon, 2 of the rectum). There were 5 men and 5 women, mean age 57.1 years (range 34-80). In 6 patients the diagnosis was performed with radiological investigations, in 4 with ultrasonography too. Endoscopy biopsy was unfit for diagnosis in the gastric localizations, while it was positive in both rectal localizations. Seven patients were operated and no postoperative morbidity or mortality was observed. The role of surgery is discussed, diagnosis for staging and therapy alone or associated with chemotherapy and/or radiotherapy. PMID- 8479655 TI - [Therapeutic approach in ventral hernia]. AB - Laparoceles are diseases of the abdominal wall and their repair does not usually involve technical problems which are difficult to resolve. The use of classic surgical methods, such as direct suture and plastic surgery, enables the parietal defect to be easily repaired in most case. However, cases do occur in which the surgeon is faced with considerable technical and tactical difficulties largely due to anatomopathological causes: the "loss of the right of domicile" of herniated viscera and the loss of musculo-aponeurotic substance. In the former case it is necessary to prepare the peritoneal cavity using pneumoperitoneum. In the event of the extensive destruction of the muscular component, or when the parietal breech is located next to bone or cartilagenous structures, it is essential to use a prosthesis. The paper goes on to describe the indications for the use of various techniques and their respective methods of use under different anatomo-clinical conditions. PMID- 8479657 TI - [Doppler color echography in the diagnosis of impotence]. AB - This study reports the experience achieved with duplex and color Doppler ultrasonography in 120 impotent patients. The following morphodynamic parameters of the cavernosal arteries were studies before and after intracorporal injection of a mixture of vasoactive drugs: arterial diameter, wall pulsatility, morphology of the spectral waveform, peak systolic velocity, end diastolic velocity and flow volume. The veno-occlusive mechanism of the corpora cavernosa was studied directly by determination of flow along the deep dorsal vein of the penis and indirectly by serial evaluation of the diastolic flow of the cavernous arteries. PMID- 8479658 TI - Hypertension and its treatment in a New Zealand multicultural workforce. AB - AIMS: To investigate ethnic variations in blood pressure levels and the likelihood of hypertension being treated in a multicultural New Zealand workforce. METHODS: An employed population of 5651 staff aged 40 to 64 years at worksites in Auckland and Tokoroa, who recorded their current prescribed medication, were measured for blood pressure, weight and height. Body mass index (BMI) was calculated. RESULTS: Mean blood pressure levels were higher in men than women, and increased with age and BMI. Compared with Europeans, mean systolic and diastolic blood pressures were higher in Maori (by 5 to 6 mmHg), Pacific Islanders (by 4 to 6 mmHg) and Asians (by 1 to 5 mmHg) after controlling for age and blood pressure treatment. This increase in Maori and Pacific Islanders, compared with Europeans, was approximately halved after also controlling for BMI, but still remained statistically significant (p < 0.05). In contrast, ethnic differences in BMI did not explain any of the blood pressure increase in Asians. In analyses restricted to hypertensive participants, the likelihood of hypertension being treated was higher in women than men (odds ratio (OR) = 3.42; 95% CI 2.13, 5.47), and lower in Maori (OR 0.33; 95% CI 0.19, 0.58), Pacific Islanders (OR 0.27; 95% CI 0.16, 0.47) and Asians (OR 0.29; 95% CI 0.10, 0.86) than Europeans. CONCLUSION: These results suggest that the likelihood of hypertension being treated is related to sex and ethnic group; and that other unknown factors, in addition to increased BMI levels, explain the higher blood pressure levels in Polynesians compared to Europeans. PMID- 8479659 TI - The patient with haematuria. PMID- 8479660 TI - Planned early discharge from New Zealand maternity hospitals. AB - AIMS: The purpose of the Plunket National Child Health Study was to establish a database on health indicators of New Zealand children and families. This paper examines the issue of early discharge in New Zealand maternity hospitals. METHODS: As part of the study, 4286 parents were interviewed when the child was around six weeks post partum regarding their planned choice for length of post natal hospital stay and their actual length of stay. RESULTS: Most New Zealand mothers choose to stay in hospital for 4-7 days following childbirth. Those mothers choosing early discharge (within 48 hours of delivery), tended to be multiparous, nonEuropean, less educated and of lower socioeconomic status. CONCLUSIONS: The characteristics of those choosing early discharge demonstrate the vulnerability of this group and also have implications for the provision of health care services which are discussed. PMID- 8479661 TI - Cervical cancer: changing trends in the Wellington region. AB - AIM: To identify changes in patient and tumour characteristics of women with carcinoma of the cervix treated through the Wellington Regional oncology unit between 1975-89. METHODS: The medical records of the patients treated between 1985-9 were reviewed. The age and stage of disease was noted in each case and results compared with the previous two 5-year cohorts. RESULTS: Over the 15 year period there was no obvious reduction in the incidence of cervical cancer. There was a significant trend towards women presenting with earlier stage disease. In the 1985-9 cohort, patients less than 40 years old were significantly more likely to present with earlier stage disease, and there was no detectable difference between the incidence of cervical cancer in Maori and nonMaori. CONCLUSIONS: The results indicate that cervical screening has not yet made an impact on the incidence of cervical cancer in the greater Wellington region, and possible reasons for this are discussed. PMID- 8479662 TI - Diabetes detection on the surgical wards in an area with a high prevalence of diabetes. AB - AIM: To describe the prevalence of diabetes and audit the processes used for diabetes detection on the surgical wards at Middlemore Hospital. METHODS: By the retrospective viewing of the notes of all admissions over a 12 month period. Comparison was made with routinely collected hospital discharge data. RESULTS: Notes from 10,893 of 11,004 (99.0%) admissions were viewed. 550 (5.0%) admissions involved a diabetic patient but diabetic patients were more likely to be readmitted (27.6% vs 13.5% diabetes vs no diabetes, chi 2 = 61.2, df = 1, p < 0.001). Only 18.2% of diabetic admissions and 24.5% of diabetic patients were identified as such on hospital discharge data. No screening for diabetes was undertaken in 34.2% of younger and 8.7% of older admissions and 7.5% of patients had either glycosuria or a glucose > or = 8.0 mmol/L but received no follow up. Only 17 new cases of diabetes were detected. Although no ethnic group difference in screening or identification of diabetes was found, in those aged > or = 60 years, 31% of Maori and 26% of Pacific Islands inpatients had diagnosed diabetes (vs 7.9% European). A similar excess of diabetes in Maori (18%) and Pacific Islands (16%) patients was found in those aged 40-59 years (Europeans 6%). CONCLUSION: In areas with a high proportion of Maori and Pacific Islands people, diabetes is an important medical condition to be considered in all surgical inpatients. Screening tests for diabetes need to be more closely followed up, perhaps by informing the general practitioner of the inpatient glucose. PMID- 8479663 TI - Lifestyle advice to pregnant patients. PMID- 8479664 TI - Wernicke's encephalopathy presenting with blindness. PMID- 8479665 TI - Cost benefit of pharmacy audit and nonrestrictive antibiotic policy. PMID- 8479666 TI - Antiarrhythmic drugs. PMID- 8479667 TI - Health messages on alcohol advertising: a positive or a counterproductive measure? PMID- 8479668 TI - Childhood asthma. PMID- 8479669 TI - Costing the HIV/AIDS epidemic. PMID- 8479670 TI - Use of ondansetron (Zofran) PMID- 8479671 TI - Safety of intravenous dipyridamole thallium myocardial perfusion imaging: experience in 435 patients. AB - Dipyridamole stress 201Tl scintigraphy is widely used in the investigation of myocardial ischaemia. We report our experience of adverse effects observed during this diagnostic procedure. A prospective study was undertaken of 435 consecutive patients (mean age 59 years; 273 males) referred to two nuclear medicine departments for assessment of myocardial perfusion was undertaken. Patients were monitored prior to and following the infusion of dipyridamole. All symptomatic, haemodynamic and electrocardiographic changes were documented. No deaths occurred in this series. Adverse events were observed in 174 (40%) patients. Of these, three patients experienced 'major' adverse events (0.6%) requiring hospitalization (myocardial infarction = 1; chest pain = 1; simple partial seizure = 1). 'Moderate' adverse events occurred in 39 (8.9%) patients and required intravenous aminophylline to reverse effects (ST segment abnormalities = 26; nausea = 7 headache = 3; chest pain = 2; bronchospasm = 1; protracted vomiting = 1; diarrhoea = 1). 'Minor' adverse events were experienced by 132 (30.3%) patients and did not require aminophylline. Sixty per cent of our patients experienced no ill effects from dipyridamole given as an exercise substitute in conjunction with 201Tl imaging. The rest had symptoms which were mostly mild, although a few patients found the experience unpleasant. Only one patient experienced a life-threatening episode. PMID- 8479672 TI - Regional distribution of 123I-(ortho-iodophenyl)-pentadecanoic acid and 99Tcm MIBI in relation to wall motion after thrombolysis for acute myocardial infarction. AB - To characterize the myocardium after thrombolytic therapy for infarction single photon emission computed tomographic (SPECT) studies with 123I-(ortho-iodophenyl) pentadecanoic acid (oPPA) and 99Tcm-methoxyisobutyl isonitrile (MIBI) were obtained at rest in nine patients within a fortnight after the acute event. A decreased oPPA activity compared to MIBI was observed in 15/45 segments (7/9 patients). The segments with discordant oPPA/MIBI activities showed less severe wall motion abnormalities than the segments with concordant decreased oPPA and MIBI activities (P = 0.004). A significant association was found between discordant oPPA/MIBI activities and the early evolution of wall motion following thrombolysis: discordant oPPA/MIBI activities were present in nine of the 11 segments (82%) with improved wall motion, while the wall motion of the seven segments with similar decreased oPPA and MIBI activities was unchanged or had deteriorated (P = 0.018). It is concluded that metabolic abnormalities often persist longer than perfusion and wall motion abnormalities soon after thrombolysis, and that 123I-oPPA in combination with 99Tcm-MIBI is useful to demonstrate myocardial areas which have been salvaged by thrombolysis. PMID- 8479674 TI - The design and construction of a central radiopharmacy. AB - Following an inspection by the Medicines Control Agency (MCA) of the existing radiopharmacy, it was necessary to design and build a new facility at the Western Infirmary to supply radiopharmaceuticals for patient use throughout the West of Scotland. This is one of the largest radiopharmacies in Europe, supplying some 40,000 patient doses per year prepared using both closed and open procedures. The design parameters and construction details of the new facility are presented. PMID- 8479673 TI - Markers of left ventricular dysfunction induced by exercise, dipyridamole or combined stress on ECG-gated myocardial perfusion scans. AB - An index of left ventricular contraction can be extracted from the cavitary time activity curve of electrocardiographic (ECG)-gated myocardial perfusion scans. To assess the induction of stress-induced myocardial depression, we compared contraction indexes derived from immediate poststress and delayed 201Tl images with indexes of ventricular dilation and lung uptake in the prediction of severe coronary artery disease (defined as two or more 90% stenoses). Stress procedures were performed in 93 patients with symptom-limited supine bicycle exercise alone, and in 227 with intravenous dipyridamole, combined where possible with exercise. The immediate and delayed contraction indexes reflected left ventricular dysfunction on ventriculography (P < 0.0001), but additionally the immediate index was reduced (P < 0.0001) in severe coronary disease. Stress-induced hypokinesis was seen frequently after each of the test modes. The relationship with angiographic findings was better defined for indexes of contraction than for lung uptake or ventricular dilation (P < 0.01). The prediction of severe coronary disease was optimized by combining the poststress contraction index and lung uptake. These data support the use of ECG-gated myocardial scans in evaluating the functional consequences of stress/imaging procedures. PMID- 8479675 TI - Use of fine needle aspiration cytology in the management of the solitary cold thyroid nodule. AB - The aim of this study was to evaluate the use of fine needle aspiration cytology (FNA) in the management of the solitary cold thyroid nodule and set up a thyroid cytology service in a district general hospital. One hundred and eight patients underwent FNA and then went on to have thyroid lobectomy. The results of cytology were compared with histology. The percentage of cancers was 8% and of benign lesions 92%. The overall accuracy of FNA was 86%. There were no false positive results and one false negative result. If one includes a suspicious cytology as positive then six of seven cancers were diagnosed by FNA. Also, 49 benign colloid nodules were accurately diagnosed by FNA and could have avoided surgery (55% of the Series). We conclude that fine needle aspiration cytology is a useful adjunct to the management of the solitary cold thyroid nodule and should be used with other clinical information to decide the best form of treatment for the patient. PMID- 8479677 TI - Democrats introduce OSHA reform bill. PMID- 8479676 TI - Scintigraphy and sonography in reflux nephropathy: a comparison. AB - The evaluation of reflux nephropathy (RNP) is a major task in the following up of children with vesicoureteral reflux (VUR). Adequate monitoring of RNP development depends on the frequent use of sonographical and scintigraphical examinations. In order to evaluate the accuracy of sonography in monitoring RNP 63 patients suffering from VUR (mean age: 8.8 years, range: newborn to 18 years, male:female = 19:44) were examined prospectively. We calculated renal size sonographically and compared our data to static and dynamic renographic findings. Our results showed a good correlation between relative DMSA uptake and sonographically estimated relative renal size (r = 0.95, P < 0.001), whereas not unexpectedly the correlation between relative kidney function and sonographically estimated renal size was poor (r = 0.83, P < 0.01). We therefore believe, that in monitoring children with VUR, sonography can offer accurate information on questions about renal size and renal parenchymal structure as well as pelvic distention. With very small kidneys as well as with kidneys showing severe dilatation and above all for evaluating renal function, scintigraphy proved to be the better method. PMID- 8479678 TI - Notes from Washington. PMID- 8479679 TI - Lead construction standard readied. PMID- 8479680 TI - Mine safety experts aim for 'zero fatalities'. PMID- 8479681 TI - Coal dust and black lung. PMID- 8479682 TI - Healthcare claims and cost analysis can reap huge dividends for employers. PMID- 8479683 TI - ASHRAE's Indoor Air Quality procedure generates the dilution ventilation rate. PMID- 8479684 TI - Case incentive plan gives safe workers 'friendly competition,' encouragement. PMID- 8479685 TI - Unheeded advice? PMID- 8479686 TI - Blueprint for health surveillance. PMID- 8479687 TI - Analytical focus reduces anxiety over CTD claims. PMID- 8479688 TI - Detecting 'fakes'. PMID- 8479689 TI - Correct PPE helps alleviate persistent back injuries, compensation expenses. PMID- 8479690 TI - Skin exposures can develop into dermatitis. PMID- 8479691 TI - Emphasize handwashing benefits. PMID- 8479693 TI - AOHC's Atlanta conference sets up debates on healthcare, safety issues. PMID- 8479692 TI - Who's protected? Legal, ethical issues in employing the immunosuppressed. AB - There does exist a growing population of immunosuppressed people who are entering or re-entering the workforce, and their impact will be felt in the future. They present unique needs that should be addressed clearly, but the waters remain muddy. How do all remain protected and at what cost? The government has established mandates for hiring and accommodating the disabled, but how does the small employer survive the financial consequences? What happens when the 16-year old bone-marrow transplant recipient cuts her hand on metal shelving at the hardware store where she works? Who is liable for the medical costs if the individual contracts an infection, or worse, tetanus? Is the individual's transplant considered a pre-existing condition? Will the employer's worker's compensation package cover the expense? Worse yet, what happens if this individual should die of complications from the injury? Who is responsible? Would the outcome be different if the employer knew the individual was immunosuppressed? Does the pre-existing condition influence the medical insurance coverage or costs? Can a truly safe environment be provided? At what cost to whom? PMID- 8479694 TI - Fibrinous iritis and IOLs. PMID- 8479695 TI - "Sterile" endophthalmitis after sutureless cataract extraction. PMID- 8479696 TI - Ultraviolet radiation damage to the corneal endothelium? PMID- 8479697 TI - Different providers and differing error rates in health care outcomes: cataract co-management at what price? PMID- 8479698 TI - Postoperative Propionibacterium endophthalmitis. Treatment strategies and long term results. AB - PURPOSE: Postoperative Propionibacterium endophthalmitis is a condition characterized by exacerbations and remissions that has often been accompanied by recurrence after treatment. The purpose of this study is to evaluate the efficacy of initial therapies in preventing recurrent endophthalmitis and to assess the safety of intraocular lens (IOL) exchange performed during treatment of active endophthalmitis. METHODS: The records of 22 patients with culture-proven Propionibacterium endophthalmitis treated at one facility were retrospectively reviewed. RESULTS: Two patients presented acutely, were treated with intraocular antibiotic injection alone, and experienced no recurrent inflammation. Twenty patients presented with chronic, delayed-onset pseudophakic endophthalmitis. Eight of these were treated initially with intraocular antibiotic injection alone, and recurrent endophthalmitis developed in seven. Twelve patients with chronic endophthalmitis were initially managed surgically with either pars plana vitrectomy or IOL exchange. Four of the 12 experienced recurrent endophthalmitis. Patients undergoing capsulectomy as part of initial management experienced the lowest rate of recurrent endophthalmitis. Eight patients eventually underwent total capsulectomy and IOL explantation, seven of whom had IOL exchange. None of these eight patients had recurrent endophthalmitis. In seven of the eight, persistent bacterial colonization of the lens capsular remnants was demonstrated. CONCLUSIONS: These data suggest that recurrent Propionibacterium endophthalmitis is due to persistence of viable organisms sequestered within lens capsular remnants, and that initial therapy directed toward surgical removal of these sequestered organisms results in a reduced frequency of recurrent endophthalmitis. Intraocular lens exchange with complete capsular removal during active endophthalmitis was not associated with recurrent or persistent endophthalmitis. PMID- 8479699 TI - Vitreous cultures in suspected endophthalmitis. Biopsy or vitrectomy? AB - BACKGROUND: Isolation of bacteria from vitreous biopsy often guides therapy in suspected endophthalmitis. Therapeutic vitrectomy provides an additional source of culture material. The authors compared the ability of these two techniques to isolate organisms from patients with acute endophthalmitis. METHODS: In a large ophthalmic microbiology laboratory during a 4-year period, the authors analyzed 206 microbial culture results from patients with suspected endophthalmitis. RESULTS: Two hundred six cases were evaluated. While cultures of vitreous biopsy specimens obtained using a needle and syringe were positive in 91 (53.8%) of 169 patients, culturing the contents of the vitrectomy cassettes produced positive cultures in 29 (74.8%) of 39 patients. Both techniques were performed on 23 patients. Vitreous biopsy allowed isolation of the causative organism in 43% of these patients, whereas vitrectomy was 76% successful. Both comparisons were significant at the P < 0.01 level. No positive vitreous biopsy cultures had associated negative vitrectomy cultures. CONCLUSION: Culturing the contents of the vitrectomy cassette significantly increases the likelihood of obtaining a positive culture compared with merely culturing a vitreous biopsy. PMID- 8479700 TI - Capnocytophaga endophthalmitis. AB - PURPOSE: This article presents three patients with endophthalmitis associated with infection with Capnocytophaga species. METHODS: The medical records of three patients with culture-positive Capnocytophaga endophthalmitis were reviewed. A panel of isolates of Capnocytophaga were then tested for sensitivity to third generation cephalosporins. RESULTS: Endophthalmitis with Capnocytophaga species developed in three patients. Infection in the setting of sepsis developed in one patient. Two other patients, one with a penetrating injury and another with keratitis in association with a corneal graft, developed mixed infection with Capnocytophaga being the predominant infecting organism by culture. Two patients recovered vision with clearance of the infection. The third patient underwent enucleation. Capnocytophaga was found to be sensitive to several of the third generation cephalosporins. To the best of the authors' knowledge, these are the first reported cases of endophthalmitis with Capnocytophaga species. CONCLUSION: Capnocytophaga species, previously shown to cause necrotizing keratitis, is a potential cause of endophthalmitis, either as a single organism or as part of a mixed infection. PMID- 8479701 TI - Suprachoroidal hemorrhage. Clinical features and results of secondary surgical management. AB - PURPOSE: The purposes of this study are to identify clinical features in eyes with suprachoroidal hemorrhage which portend a poor visual prognosis and to determine visual outcome in these eyes after secondary surgical management of suprachoroidal hemorrhage. METHODS: This was a retrospective study of 106 patients with suprachoroidal hemorrhages occurring in association with trauma (35), cataract surgery (30), glaucoma surgery (17), penetrating keratoplasty (6), corneal perforation (5), secondary lens implantation (3), pars plana vitrectomy (3), and other causes (7). RESULTS: Five (10%) of 49 eyes with a suprachoroidal hemorrhage and an initial retinal detachment had a visual outcome of 20/200 or better compared with 21 (43%) of 49 eyes without a retinal detachment. The presence or absence or a retinal detachment could not be determined in eight patients and all eight of these patients had a poor visual outcome. Sixteen (20%) of 82 eyes with a 360 degrees suprachoroidal hemorrhage had a visual outcome of 20/200 or better compared with 10 (47%) of 21 for those with suprachoroidal hemorrhage limited to one or two quadrants. The extent of the hemorrhage could not be determined in three eyes. Overall, 34% (14/41) of the patients with suprachoroidal hemorrhage who had a secondary surgical procedure achieved a visual outcome of 20/200 or better. Forty-three percent (6/14) who had a suprachoroidal hemorrhage during or after cataract surgery and who were treated with secondary surgical management achieved a visual outcome of 20/200 or greater. CONCLUSION: Clinical features associated with a poorer visual outcome included initial or indeterminate retinal detachment and 360 degrees suprachoroidal hemorrhage. Limited suprachoroidal hemorrhage without initial retinal detachment usually has a good visual prognosis and does not usually require secondary surgical intervention. However, if the former complication is present, secondary surgical intervention should be considered. PMID- 8479702 TI - Cryotherapy during surgery for giant retinal tears and intravitreal dispersion of viable retinal pigment epithelial cells. AB - BACKGROUND: Retinal pigment epithelial (RPE) cells are a major component of contractile cellular membranes in proliferative vitreoretinopathy (PVR). Displacement of viable RPE cells into the vitreous cavity is necessary for membrane formation. This study examines the effect of cryotherapy during surgery for giant retinal tears on the dispersion of viable cells into the vitreous cavity. METHODS: A total of seven eyes undergoing vitrectomy and retinal reattachment surgery were studied. Vitreous fluid from three eyes was aspirated immediately after cryotherapy; fluid from four eyes was aspirated after scleral indentation with the cryoprobe, but without cryotherapy. Colonies of pigmented cells routinely grew in flasks inoculated with fluid from eyes treated with cryotherapy. In contrast, flasks inoculated with fluid from eyes not treated with cryotherapy contained significantly fewer viable cells. CONCLUSION: Cryotherapy performed during retinal reattachment surgery in eyes with giant retinal tears is likely to enhance intravitreal dispersion of viable RPE cells. The findings in this study suggest that possible harmful effects of cryotherapy should be evaluated further and that alternative methods of creating a chorioretinal adhesion should be considered in cases with an especially high risk of PVR. PMID- 8479703 TI - Retinal vascular changes in congenital hypertrophy of the retinal pigment epithelium. AB - BACKGROUND: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a well-defined clinical entity with usually well-delineated, pigmented oval or round lesion with smooth or scalloped margins. Occasional retinal vascular changes have been reported previously. PURPOSE AND METHOD: To assess the prevalence of these changes, the authors performed a retrospective analysis of 12 patients with CHRPE, for whom fluorescein angiography allowed visualization of the entire lesion and of the retinal vascular capillary bed. RESULTS: Retinal vascular changes were found in 11 (91%) of these 12 patients. The changes consisted of capillary rarefaction in all 11 patients, with areas of capillary nonperfusion exceeding 1 disc diameter (DD) in three patients (25%), micro aneurysmal capillary dilatations in three (25%), and chorioretinal anastomosis in one. CONCLUSION: These results suggest that the above changes could constitute clinical and angiographic characteristics of CHRPE and allow easy corroboration of its diagnosis, thus avoiding the need for further clinical investigations. PMID- 8479704 TI - Effect of transposition surgery on rectus muscle paths by magnetic resonance imaging. AB - PURPOSE: To evaluate effects of transposition on extraocular rectus muscle paths in middle and deep orbit. METHODS: The effect of various transposition procedures was assessed in five patients, using surface coil magnetic resonance imaging (MRI), performed with controlled gaze before and after surgery. Path changes were compared with those expected under conventional concepts of functional orbital anatomy, quantified by biomechanical modeling. RESULTS: Vertical rectus transpositions of 6 to 10 mm produced changes in muscle paths of 3 mm or less, assessed posterior to the equator of the globe. Lateral rectus transpositions as large as 10 mm resulted in almost no movement of muscle bellies. Conventional modeling predicted much larger changes. CONCLUSION: The authors observed less movement of rectus muscle bellies relative to orbital walls than would be expected under the traditional assumption that transposed muscles follow the shortest path from origin to insertion. This implies that middle and deep orbital tissues (connective tissues and compartmentalized orbital fat) constrain the paths of rectus muscle bellies, preventing them from sliding freely to follow their transposed insertions. The authors propose that these tissues function as "pulleys" elastically coupled to the orbital wall, and that they are important determinants of extraocular muscle function. PMID- 8479705 TI - The Teller acuity card procedure. Three testers in a clinical setting. AB - PURPOSE: The Teller acuity card procedure provides a quantitative measure of grating acuity in infants and young children and has been used in clinical and laboratory settings. The purpose of this study is to address the influence of the individual testers in a clinical setting. The authors report a comparison of acuity results obtained by three well-trained, experienced testers in a busy hospital-based clinical practice. METHODS: Three different testers (A, B, C) performed 971 consecutive acuity assessments using the Teller acuity card procedure on 570 patients. The testers used similar techniques and adaptations, depending on clinical need. Diagnostic categories include nystagmus, aphakia, strabismus, glaucoma, retinopathy of prematurity (ROP), ptosis, optic nerve abnormalities, etc. Patients ranged in age from 2 weeks to 17 years (mean +/- standard deviation, 23 +/- 20 months). RESULTS: When each patient was represented only once, A tested 144 patients; B, 251; and C, 175. The geometric mean right eye acuity scores of A were 3.00 cycles/degree (cy/deg) (0.34 octaves, standard error [SE]; n = 134); B, 4.05 cy/deg (0.20 octave, SE; n = 225); and C, 3.71 cy/deg (0.30 octave, SE; n = 163). An analysis of covariance showed a significant difference in the mean log scores across testers (P = 0.02 adjusted for both age and diagnosis). Age was a strong predictor of acuity (P = 0.0001), and the interactions between tester and age and tester and diagnosis were not significant. The geometric mean left eye acuity scores for A were 2.86 cy/deg (0.33 octave, SE; n = 132); B, 3.46 cy/deg (0.23 octave, SE; n = 218); and C, 3.32 cy/deg (0.30 octave, SE; n = 160). The differences for left eyes among testers were not significant (P = 0.37 adjusted for age and diagnosis). CONCLUSIONS: These results suggest that the tester may influence the acuity results measured by the Teller acuity card procedure in a clinical setting. Evaluation of interobserver reliability in clinical subjects should be a high priority of further work using the Teller acuity card procedure. PMID- 8479706 TI - Distance stereoacuity. Assessing control in intermittent exotropia. AB - BACKGROUND: A patient's ability to control an intermittent exotropic deviation is usually assessed by subjective means such as observation of control in the office, questioning the patient and/or family about control at home, and reports of monocular eye closure in bright light. An objective method of assessing control has not been developed. PURPOSE: The purposes of this study are to determine if distance stereoacuity was different in patients with intermittent exotropia than in normal subjects and to determine if distance stereoacuity could be used as a objective means of assessing control in intermittent exotropia. METHODS: The authors evaluated near and distance stereoacuity in 44 patients with intermittent exotropia and 50 normal subjects. Patients with intermittent exotropia also were assessed for office control, home control, and monocular eye closure in bright light. Additionally, six patients who underwent successful surgery were reevaluated postoperatively. CONCLUSION: Normal subjects and patients with intermittent exotropia had good near stereoacuity. Patients with intermittent exotropia demonstrated significantly worse distance stereoacuity than the population of normal subjects (P < 0.001). Five of six patients with poor distance stereoacuity preoperatively had dramatic improvement in distance stereoacuity postoperatively. Diminished distance stereoacuity seems to be an objective measure of poor control of the exotropic deviation. This test may provide important objective criteria for deciding when to perform surgery in patients with intermittent exotropia. PMID- 8479707 TI - Extraocular muscle involvement in sarcoidosis. AB - BACKGROUND: Sarcoidosis is a granulomatous inflammatory disease that may have a variety of ocular and orbital manifestations. The most common ocular manifestation is uveitis, and the most common orbital manifestation is dacryoadenitis. Extraocular muscle involvement in sarcoidosis has rarely been reported. The authors report a case of sarcoidosis involving the extraocular muscles of a 15-year-old boy with bilateral, painful, external ophthalmoplegia and enlargement of all extraocular muscles on computed tomography (CT) scan. RESULTS: Lateral rectus muscle biopsy and transbronchial lung biopsy showed noncaseating granulomas characteristic of sarcoidosis. Cultures and serologic studies excluded fungal and mycobacterial diseases. Treatment with oral corticosteroids improved symptoms and signs. CONCLUSIONS: The authors report the first case of sarcoidosis in a patient with symptomatic extraocular muscle involvement, and only the third case in which extraocular muscle involvement has been shown histologically. PMID- 8479708 TI - Retrobulbar anesthesia risk. Do sharp needles really perforate the eye more easily than blunt needles? AB - PURPOSE: Conventional wisdom in ophthalmology is that the force required to perforate an eye during retrobulbar injection is noticeably greater with a specially designed blunt needle than with a standard hypodermic needle. A search of the literature showed no measurements of scleral perforation pressure with specific needle tips. The authors investigated this concept. METHODS: A computerized search for eye perforations of the surgical records over a 5-year period at Wilford Hall United States Air Force Medical Center was conducted. A double-masked trial by experienced ophthalmologists, using preserved eye bank eyes and several commercially available needles, subjectively assessed the force required to perforate the globe. The authors designed and built a portable transducer system to objectively measure the perforation pressure of human globes with the needles. Measurements were done with preserved and unpreserved human cadaver eyes. RESULTS: No globe penetrations or perforations were found in this consecutive series of over 4000 retrobulbar anesthesia procedures. A subjective difference between the hypodermic and blunt needles was detected. Objective measurements showed a significant difference between the hypodermic and blunt needles, and between types of blunt needles. The difference was present with both eye bank eyes and fresh cadaver eyes. CONCLUSIONS: Blunt-tipped needles do require greater force to penetrate the eye. The noncutting edge, blunt-tipped needles have higher scleral perforation pressures than those with cutting edges. PMID- 8479709 TI - The effect of simulated cataract on the glaucomatous visual field. AB - PURPOSE: The current study is designed to determine the effect of light scattering (simulated cataract) on glaucomatous visual fields. METHODS: Twelve patients with relative scotomas caused by glaucoma underwent the 30-2 threshold test with the Humphrey Visual Field Analyzer twice: once with and once without having a light-diffusing piece of ground glass in front of the eye, which, in previous experiments, has been shown to decrease perimetric threshold by 4.4 decibels (dB) in normal eyes. As controls, 12 patients underwent the same examination with and without a piece of clear glass in front of the eye. In each pair of fields, five points were analyzed within the relative scotoma and compared with five points in a normal area of the opposite hemifield. RESULTS: The diffusing ground glass produced a mean decrease of perimetric threshold of 5.7 dB (standard deviation [SD] = 3.3 dB) within the area of relative scotoma compared with 6.1 dB (SD = 2.4 dB) within the normal area and 4.4 dB (SD = 2.25 dB) at the fovea. The differences between means were not statistically significant. In addition, the diffusing glass did not affect the corrected pattern SD (CPSD) index (6.5 dB with the diffuser and 6.5 dB without). CONCLUSION: Light scattering depresses the glaucomatous visual field diffusely. Relative glaucomatous scotomas and normal areas are depressed equally, expressed as change in decibel of sensitivity. Therefore, in following patients with cataracts and glaucoma, depression of threshold sensitivity in glaucomatous areas out of proportion to normal areas should not be attributed to the light scattering effect of the cataract, but rather to possible worsening of glaucomatous damage. PMID- 8479710 TI - Priority of test locations for automated perimetry in glaucoma. AB - PURPOSE: Static threshold automated perimetry is a demanding test which can be tiring for some patients. The authors investigate how to optimize early stages of the test which can shorten examination time and improve performance. The effectiveness of measuring every point twice to improve diagnostic precision (proportion of eyes correctly diagnosed as normal or glaucomatous) also was evaluated. METHODS: The authors evaluated the relative contributions of individual test locations to the sensitivity and specificity of static threshold perimetry. One hundred visual fields (Octopus Program G1) of 100 patients with open-angle glaucoma and early glaucomatous defects were used to rank the most frequently defective test locations. This sequence was modified so that highly correlated points were not ranked together. The sensitivities and specificities of the defined sequence of test presentations were then measured in a separate database of 70 normal controls and 70 patients with early glaucomatous visual field defects. RESULTS: Sensitivity and specificity were, respectively, 80% and 80% after 12 locations, 89% and 89% after 26 locations, and 97% and 99% after all 59 test locations. The information obtained with the first phase alone approximates that of both phases. CONCLUSION: Staging of locations tested with automated perimetry in glaucoma may be a valuable method to reduce examination time, minimize fatigue effects, and optimize diagnostic information. Retesting every point does not improve diagnostic precision. PMID- 8479711 TI - Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma. AB - BACKGROUND: Juvenile glaucoma is an uncommon form of open-angle glaucoma that is usually recognized during childhood or early adulthood and which often has a strong family history. METHODS: The authors clinically characterized a large multigeneration family with autosomal-dominant, juvenile-onset, open-angle glaucoma. Linkage analysis with short tandem repeat polymorphisms was used to evaluate the Rieger's syndrome locus as the site of the disease-causing mutation. RESULTS: Forty members of a family with a five-generation history of open-angle glaucoma were examined. Clinical data were available from an additional five individuals, three of whom were decreased. Older family members provided limited information about the visual history of five other deceased individuals in the first three generations. Fifty-nine people were at 50% risk of harboring the disease-causing mutation; and of these, 30 were affected with glaucoma by examination or by family history. All affected patients had an affected parent. The average age at diagnosis was 18 years (range, 8-30 years). Affected family members tended to be myopic but lacked other ocular or systemic abnormalities. The intraocular pressures (IOPs) of affected individuals were commonly more than 50 mmHg when they were first examined. Gonioscopy showed the angles to be open, with no abnormal pigmentation, iris processes, or embryonic tissue. Topical medications were initially effective in controlling IOP, but surgery was usually required for long-term pressure control. The Rieger's syndrome locus on chromosome 4q25 was excluded as the site of the disease-causing mutation. CONCLUSION: Juvenile open-angle glaucoma can occur as an autosomal dominant trait with high penetrance. Genetic linkage analysis of the family reported here has the potential to identify the chromosomal location of a glaucoma-causing gene. This gene is genetically distinct from the chromosome 4 locus that was recently associated with Rieger's syndrome. PMID- 8479712 TI - Results of therapeutic penetrating keratoplasty. AB - PURPOSE: To determine the anatomic and visual results of therapeutic penetrating keratoplasty (PK) and its role in the management of corneal disease. METHODS: The authors reviewed the records of all of their patients who had undergone therapeutic PK over the past 9 years and evaluated each for the following criteria: cure of disease, graft clarity, and visual acuity. Patients were divided into seven categories: (1 and 2) bacterial and fungal keratitis, (3 and 4) herpetic keratitis, with and without inflammation, (5) acanthamoebic keratitis, (6) perforations due to keratoconjunctivitis sicca, and (7) other causes of perforation. RESULTS: In microbial keratitis, therapeutic PK eradicated the disease in all cases. Seventy-three percent of grafts for bacterial keratitis and 60% for fungal keratitis remained clear. A higher percentage of clarity was achieved when grafts were 9.0 mm or less. Seven patients with secondary endophthalmitis were cured with a surgical approach including therapeutic PK. In herpetic keratitis with active inflammation, only 36% of grafts remained clear, and inflammation recurred in 36%. All perforations due to post-herpetic persistent epithelial defects in "quiet" eyes were grafted successfully. In patients with severe keratoconjunctivitis sicca, eyes were anatomically stabilized in 83%, but all grafts failed because of complications from ocular surface disease. CONCLUSIONS: Therapeutic PK is valuable in the management of microbial keratitis that does not respond to antimicrobial therapy. Results are poorer for patients with herpetic keratitis, although selected patients respond to therapeutic PK when other methods of management have failed. Patients with perforations due to keratoconjunctivitis sicca have a uniformly poor prognosis for graft clarity. PMID- 8479713 TI - A prototype erodible mask delivery system for the excimer laser. AB - PURPOSE: The authors developed an erodible mask delivery system for the argon fluoride 193-nm excimer laser, which offers the possibility of correcting hyperopia and astigmatism as well as myopia. METHOD: Masks were made of polymethylmethacrylate on a quartz window, with intended corrections for myopia and hyperopia of 2.5 and 5 diopters (D). Ablations using the mask and control ablations using an expanding diaphragm were performed in 30 eyes of 15 pigmented rabbits with an Excimed UV200 laser (Summit Technology, Inc, Waltham, MA). The rabbits were followed for 134 days with regular biomicroscopy and retinoscopic examination by two observers. RESULTS: Ablations with the mask to correct myopia were successful and produced stable corrections, although the higher-power mask produced undercorrections. Hyperopic masks produced paradoxic myopic corrections, possibly due to the lack of a transition zone at the edge of the mask. Corneas ablated with the mask had less sub-epithelial haze than those ablated with the diaphragm at all examinations. Results of histopathologic examination showed epithelial hyperplasia over the ablation zone in all eyes. Dichlorotriazinyl aminofluorescein collagen staining showed subepithelial new collagen in all eyes, but there was no relation between the depth of ablation at any point on the cornea and the amount of new collagen deposited there. CONCLUSIONS: Myopic ablations are feasible with the erodible mask, although additional calibration is needed. Hyperopic ablations were unsuccessful with the current design. Corneas ablated with the mask may be clearer than corneas ablated with the diaphragm, possibly due to a smoother ablated surface. Regression of effect after laser ablation in the rabbit model is likely due more to epithelial hyperplasia than to stromal remodeling. PMID- 8479714 TI - Visual prognosis in giant cell arteritis. AB - PURPOSE: The visual prognosis in giant cell arteritis (GCA) was evaluated over a 5-year period. METHODS: The authors reviewed the records of all patients with a diagnosis of GCA established at the Mayo Clinic over a 5-year period regarding visual status. Follow-up data for these patients were obtained 5 years later. RESULTS: Of the 245 patients studied, 34 (14%) permanently lost vision because of GCA. In 32 of these patients, the visual deficit developed before glucocorticoid therapy for GCA was begun; in the 2 other patients, the visual loss occurred after the diagnosis was made and therapy was started. Visual loss progressed in three patients after initiation of oral glucocorticoids, and in five other patients vision improved. After 5 years, the probability of loss of vision developing after initiating oral glucocorticoid treatment was determined to be 1% (Kaplan-Meier technique), and the probability of additional loss was 13% in patients with GCA who had a visual deficit at the time therapy was begun. CONCLUSION: The development or progression of visual loss was rare after the initiation of glucocorticoid therapy. PMID- 8479715 TI - A new ultrasonographic method to detect disease activity and predict response to immunosuppressive treatment in Graves ophthalmopathy. AB - PURPOSE: To determine whether the internal reflectivity of the eye muscles on A mode ultrasonography serves as indicator for disease activity in Graves ophthalmopathy, thereby predicting response to immunosuppressive treatment. METHODS: Eye muscle reflectivity, expressed as percentage of the initial scleral spike, was measured in the superior, medial, and lateral recti, and normal values were determined in 23 healthy controls. These were compared with values in 16 consecutive patients with untreated, moderately severe Graves ophthalmopathy. The accuracy of the measurement was assessed by calculating the intra- and interobserver coefficient of repeatability. Baseline eye muscle reflectivity in the 16 patients was correlated to the therapeutic outcome 24 weeks after start of immunosuppressive therapy. The response to treatment served as indicator for pretreatment disease activity. RESULTS: Eye muscle reflectivity could be measured reliably, with an intraobserver coefficient of repeatability of 8.2% in controls and 10.2% in patients. Patients had lower reflectivity than controls (54.6 +/- 17.4% versus 70.7 +/- 6.6%; P < 0.001). Reflectivity in eye muscles with the lowest echogenicity was lower in responders than in nonresponders (25.8 +/- 8.4% versus 40.6 +/- 13.6%; P = 0.02). From the individual data, a cut-off value of 40% was derived, which appeared as an accurate predictor of outcome (positive predictive value 73%; 95% confidence interval 39%-94%). CONCLUSIONS: Measuring eye muscle reflectivity in Graves ophthalmopathy appears to be a reliable new method to determine disease activity, with a promising accuracy in predicting therapeutic outcome of immunosuppressive treatment. PMID- 8479716 TI - Orbital infarction syndrome. AB - BACKGROUND: The authors define orbital infarction as ischemia of all intraorbital and intraocular structures. It is a rare disorder due to the rich anastomotic vascularization of the orbit. PATIENTS: The authors report three patients with orbital infarction with similar clinical presentations: acute blindness, orbital pain, total ophthalmoplegia, and anterior and posterior segment ischemia. RESULTS: Etiologies of orbital infraction syndrome include occlusion of the common carotid artery (case 1), giant-cell arteritis (case 2), and mucormycosis (case 3). CONCLUSION: Three cases discussed in this article illustrate that orbital infarction is a disorder that can occur secondary to different mechanisms such as (1) acute perfusion failure (e.g., common carotid artery occlusion [possibly combined with anomalous orbital anastomotic channels]), 2) systemic vasculitis (e.g., giant-cell arteritis), and (3) orbital cellulitis with vasculitis (mucormycosis). The blindness and retinal and optic nerve damage were permanent, whereas the other signs of orbital ischemia (ophthalmoplegia and anterior segment ischemia) resolved. Therefore, diagnosis of orbital infarction can best be made during the acute phase. PMID- 8479717 TI - Scleral melt after cryotherapy for conjunctival melanoma. AB - BACKGROUND: The authors report a patient with a cryotherapy-induced scleral melt after combined excision and cryotherapy of a conjunctival melanoma arising within primary acquired melanosis with atypia. FINDINGS: In a 65-year-old white man, a severe scleral melt developed within 1 month of complete excision of a superficial conjunctival melanoma combined with double-freeze-thaw nitrous oxide cryotherapy to the scleral bed and surrounding conjunctival margins. Ultrasound biomicroscopy showed the degree of scleral thinning. CONCLUSIONS: Although many complications associated with cryotherapy have been described in the literature, there are no reports of a scleral melt. Scleral melt is a potential complication of cryotherapy that can occur despite taking precautions and should be monitored in the first few weeks after cryotherapy to the scleral bed of excised conjunctival tumors. PMID- 8479718 TI - The rationale for precise management of distal radius fractures. AB - Fractures of the distal radius continue to be one of the most common skeletal injuries treated by orthopedic or trauma surgeons. These injuries account for one sixth of all fractures seen and treated in emergency rooms. The rapid expansion of knowledge regarding the functional anatomy of the hand and wrist, the recognition by treating physicians of the ever increasing functional demands of senior citizens, and improved methodologies of achieving and maintaining anatomic restoration of these fractures have generated a renewed interest in addressing these fractures in a more precise manner. PMID- 8479719 TI - Fractures of the distal radius. A modern treatment-based classification. AB - The classification of fractures is necessary to make a proper assessment of the injury and to recommend appropriate treatment. This article presents a treatment based classification that assists in directing treatment. It is straight forward and easy to remember, yet has the potential for expansion to more detailed subclassifications as desired. Specific treatment planning can result from reference to this classification. PMID- 8479720 TI - Imaging techniques for distal radius fractures and related injuries. AB - In patients with distal radius fractures, routine roentgenographic examination in at least two or three planes should be performed first and is usually sufficient for correct diagnosis and adequate treatment. A careful examination of the soft tissues of the forearm and wrist on conventional roentgenograms may be key for correct diagnoses. Routine roentgenographic examination of the wrist, preferable in four views, should be performed in every patient with a distal radius fracture acutely as well as at follow-up. The technique is easy to perform, universally available, and inexpensive. Advanced imaging techniques such as radionuclide bone imaging, CT, or MR imaging should not be first choice modalities in patients with distal radius fractures and should be used only when conventional roentgenograms are inconclusive. Scintigraphy can be helpful for diagnosing occult fractures, for documenting fracture healing and ligamentous or cartilaginous post-traumatic disorders, as well as for diagnosis and follow-up of reflex sympathetic dystrophy. A disadvantage of scintigraphy is its poor specificity. Indications for CT include the confirmation of occult fractures suspected on the basis of the findings of physical examination and focally hot bone scintigrams when plain films are normal or inconclusive. In comparison with conventional radiography, CT is superior for the preoperative evaluation of complex comminuted distal radius fractures, depicting the distal radial articular surface and size and position of fracture fragments, as well as for the assessment of fracture healing. Additionally, CT is the imaging technique of choice for the correct diagnosis of subluxations of the distal radioulnar joint. Magnetic resonance imaging is an important diagnostic technique for the evaluation of suspected injuries of soft tissues related to distal radius fractures, such as to the flexor and extensor tendons or the median nerve, and for the early diagnosis of necrosis of the scaphoid or lunate. Other indications include identification of triangular fibrocartilage complex perforations, ruptures of carpal ligaments, and demonstration of contents of the carpal tunnel. PMID- 8479721 TI - Extra-articular fractures of the distal radius. AB - Extra-articular distal radius fractures frequently are undertreated. Results correlate directly with restoration of anatomy. Immobilization in plaster is an inferior method of preserving radial length and palmar tilt. Failure to maintain reduction with plaster can be predicted by the initial injury, if reduction is lost, closed reduction of the redisplaced fracture should be accompanied by external fixation. PMID- 8479722 TI - Distal radius fractures: patterns of articular fragmentation. AB - Distal radius articular fractures principally result from the die-punch mechanism of injury that leads to consistent patterns of articular disruption with readily identifiable radiographic signs of instability and reducibility. In the vast majority of articular fractures, prompt recognition of these key radiographic features serves as a sound basis for optimal management. Whereas the type I stable injury can be managed by short-term immobilization, the most frequently encountered type II unstable die-punch fracture requires stabilization provided by external fixation, frequently coupled with percutaneous internal fixation, to maintain an accurate reduction. Restoration of articular congruity in an irreducible type IIB dorsal die-punch fracture, in contrast, can only be accomplished by open treatment, usually comprising a limited exposure for reduction and internal fixation of the radiocarpal articular surface, supplementary external fixation, and adjunctive iliac bone grafting. The irreducible type IIB articular fracture with volar displacement is most suitable for stabilization by plate and screw fixation; however, in patients with excessive comminution, Kirshner wires provide a satisfactory alternative method of fixation. The type III spike fragment is secured with either small screws or wires in conjunction with closed or limited open articular restitution and appropriate nerve and tendon surgery. The irreducible type IV fracture demonstrating wide separation of articular components always requires extensive open treatment for restoration of articular congruity as well as repair of associated skeletal and soft tissue injuries. In the type V explosion injury, provisional stabilization employing, external fixation provides a sturdy framework for critical revascularization or resurfacing procedures and serves to maintain radial alignment before definitive articular reconstruction. In more severe injuries, early detection and repair of frequent periarticular injuries are essential for a favorable recovery. In those fractures requiring open reduction with internal fixation, supplementary external fixation and iliac bone grafting have proved to be increasingly beneficial adjuvants to management. In all cases, preservation of articular congruity with precise restoration of key medial fragments is the principal prerequisite for a successful outcome. PMID- 8479723 TI - External fixation of distal radius fractures. Indications and technical principles. AB - External fixation of unstable intra-articular fractures of the distal radius has become an effective tool in the management of these difficult injuries. Careful assessment of the fracture pattern, appropriate patient selection, meticulous surgical technique, the appropriate choice of fixation device and pins, recognition of the need for augmentation with limited internal fixation or bone grafting, and aggressive postoperative rehabilitation provide the foundation for successful management of these fractures while minimizing complications. The surgeon must remember that the pin-bone interface is the link between the patient and the fixator. He or she must ensure a stable environment for this interface by providing a clean, tight purchase of the pin in bone with minimal damage to the bone and its surrounding soft tissues at the time of operation. Postoperatively, the surgeon must convey to the patient the importance of maintaining a healthy environment for this pin-bone interface. An appropriately chosen external fixation device can be expected to provide overall stability while maintaining length as well as angular and rotational alignment. However, it cannot be expected to provide precise small fragment control and restoration of articular congruity. This must be achieved by precise reduction and limited internal fixation using Kirschner wires while prevention of late collapse is afforded by subarticular bone grafting of the metaphyseal defect. Adherence to these principles should provide a satisfactory outcome with a significant reduction in the rate of complications when external fixation is used for the management of complex fractures of the distal radius. PMID- 8479724 TI - External fixation. Technical advances based upon multiplanar ligamentotaxis. AB - The principle of ligamentotaxis obtained by longitudinal traction is useful in restoring skeletal length to distal radial fractures. Using external skeletal fixation to translate the hand in radial-ulnar and dorsal-palmar directions, ligamentotaxis in two additional planes aligns and tilts the distal radial fragment and its articular surface. Following restoration of palmar tilt by palmar translation, wrist position can be adjusted into neutral or extension to help avoid finger stiffness and carpal tunnel syndrome without compromising fracture reduction. PMID- 8479725 TI - Unstable articular fractures of the distal radius. Comparative techniques of ligamentotaxis. AB - Ligamentotaxis employing either pins and plaster or external fixators, frequently in conjunction with supplemental Kirschner wire internal fixation, has proved to be a reliable means of maintaining an accurate reduction of unstable articular fractures of the distal radius. Critical preoperative evaluation and surgical restoration of articular congruity along with attention to key technical details have resulted in a reproducible successful recovery. In our experience, the advantages of the pins and plaster technique are its relatively simple methodology, its comparatively low cost, and its high level of patient acceptance. The distinctive advantages of the external fixator are its superior mechanical efficiency, its capacity for fracture adjustment during the healing period, and the fact that it ensures unimpeded access to wounds. Nonetheless, regardless of the specific method chosen, this study clearly supports the contention that precision in patient selection and pin placement are the prerequisites for successful ligamentotaxis in the management of distal radius fractures. PMID- 8479726 TI - The history and evolution of percutaneous pinning of displaced distal radius fractures. AB - This article discusses the history and evolution of percutaneous pinning of displaced distal radial articular fractures. Six distinct methods are examined from an historical viewpoint, focusing on problems associated with each technique. The evolution of the Kapandji technique to include arum nuts and the Rayhack technique to include an alignment jig and pin guide with locking set screws is presented also. PMID- 8479727 TI - Intrafocal (Kapandji) pinning of unstable fractures of the distal radius. AB - Intrafocal pinning of distal radius fractures was described first by Kapandji in 1976. The technique has been used widely in Europe but remains relatively unknown in the United States. It is indicated in unstable distal radius fractures without significant intra-articular displacement. This article provides a review of the European experience, a description of the surgical technique, and an analysis of our own clinical series. Intrafocal pinning works best in patients less than 65 years of age, for the fracture patterns described previously. It provides the surgeon with a simple and effective, minimally invasive method of improving alignment and stability of unstable fractures. PMID- 8479728 TI - Indications and techniques of open reduction. Internal fixation of distal radius fractures. AB - Complex distal radius fractures present in a variety of patterns that differ by the area and degree of involvement of the articular and metaphyseal fracture components. No single method of treatment is appropriate for all fractures. This article discusses the types of fractures that either require or are best handled by formal open reduction and internal or external fixation. PMID- 8479729 TI - Concomitant skeletal and soft tissue injuries. AB - The diagnosis and treatment of those injuries most commonly seen in conjunction with distal radius fractures are reviewed in this article. Concomitant tendon, arterial, and nerve injuries often are associated with a high-energy mechanism of trauma. These injuries may complicate an already difficult fracture care plan, especially if the diagnosis of these injuries is delayed. Late tendon rupture and intercarpal injuries are discussed also. PMID- 8479730 TI - Distal forearm fractures in children. Complications and surgical indications. AB - Appropriate indications for operative management of pediatric distal forearm fractures include: 1. Compartment syndrome for fasciotomy. 2. Open fractures for irrigation and debridement. 3. Soft tissue/nerve entrapment. 4. Displaced intra articular physeal fractures. 5. Displaced or angulated fractures when the patient is close to skeletal maturity. 6. Correction of physeal arrest with malalignment or malrotation. 7. Gross displacement with cosmetic deformity. PMID- 8479731 TI - Reconstructive procedures for malunion and traumatic arthritis. AB - Despite the fact that surgical management of fractures of the distal radius has become more aggressive, leading to substantial improvement of anatomic results, malunion and post-traumatic arthritis remain the two most common complications following conservative treatment. Techniques, operations, and salvage procedures are discussed in this article. PMID- 8479732 TI - Management and rehabilitation of distal radius fractures. AB - Distal radius fractures require precise medical treatment, therapeutic intervention during fracture immobilization, and specialized rehabilitation thereafter to ensure an optimal functional result. With an understanding of the mechanics of distal radius fractures, surgical intervention, and bone healing, the therapist can modify the therapy program according to the patient's individual needs. The therapeutic process is begun in the crucial stage of bone healing during fracture immobilization. By addressing edema reduction and early range of motion of the uninvolved joints, most problems can be avoided before cast or fixator removal. Rehabilitation following the immobilization period should focus on regaining wrist movements provided that earlier problems have been addressed properly. During the rehabilitative process, the therapist can incorporate scar management, modalities, joint mobilization, active and passive range of motion, splinting, and strengthening to maximize the patient's functional result. PMID- 8479733 TI - [Laparoscopic cholecystectomy]. AB - Traditional cholecystectomy has been the standard surgical treatment of the gallstone disease for more than 100 years. The technical development led to a new surgical procedure and its rapid acceptance. This is laparoscopic cholecystectomy. Its application is becoming widespread in therapy too. But most of the surgeons are lack of technical experiences in this field. Currently it restricts the indications those are anyway the same of standard cholecystectomy. Besides its many advantages, laparoscopic cholecystectomy has its own disadvantages and being an invasive procedure, there are possibilities of complications. The latest can be reduced by the adequate choice of patients, the careful learning of the operative technic and by turning to open surgery (conversion) when it is necessary. Its morbidity is nearly equal to complications of standard cholecystectomy, but mortality rate is lower (0.05-0.2%). Our morbidity of performed 300 laparoscopic cholecystectomies was 6.4%. We had no death. The hospitalization became as short as 4 days. Our early clinical results (90%) are the same of traditional cholecystectomy. Laparoscopic cholecystectomy as a new surgical procedure involves the efficiency of the standard cholecystectomy and the noninvasive endoscopic technic. Laparoscopic cholecystectomy performed by well trained surgeons is a safe surgical procedure, its early results are excellent and makes the choice of surgical treatment, used in bile surgery richer. PMID- 8479734 TI - [Amanita phalloides poisoning in a 15-year case load of a pediatric intensive care unit]. AB - The clinical course of eight patients with Amanita phalloides poisoning is reviewed. Early diagnosis was based on the history, characteristic clinical features and non-specific laboratory data. A complex supportive therapy with gastric lavage, bowel irrigation, correction of volume and electrolyte abnormalities, and penicillin-G (Penicillin, Biogal), silibinin (Legalon SIL, Madaus), thioctacid (Thioctacid, Asta), corticosteroid (Di-Adreson-F aquosum, Organon) administration was commenced in every cases before identification of the mushroom. Haemoperfusion was performed in six cases, and in one patient plasmapheresis was applied as well. Seven children recovered completely. Unfortunately, a girl of 12 years died. According to the authors' experience, the use of non-invasive and invasive methods of the non-specific detoxication is proposed in case of severe Amanita phalloides poisoning. PMID- 8479735 TI - [Zinc excretion in osteoporotic women]. AB - Urinary zinc excretion was detected in 24 normal and 25 age matched osteoporotic women. The osteoporotic group was classified in two groups on the basis of bone mineral density (BMD) measurements. Urinary zinc excretion was 327 micrograms/g creat. in healthy subjects and 488 micrograms/g creat. in the "common porotic group". In the "trabecular porotic group" (decreased BMC with DEXA at the lumbar spine alone or together with the femoral neck, but with normal radius BMD) it was 455 micrograms/g creatinine while in the "cortical porotic group" (decreased BMD with SPA at the radius midshaft and/or all the sites measured) the zinc excretion was even higher, 588 micrograms/g creat. The difference between the normal and porotic groups was statistically significant, while within the porotic groups it was not, however the tendency was remarkable. A close significant correlation exists between BMC of radius and urinary zinc excretion. In the osteoporotic group the urinary calcium excretion was significantly higher, than in normal group (220.2 vs 145.2 mg/g creat, p < 0.01). The correlation between the urinary zinc and calcium excretion was not significantly statistically. Elevated urinary zinc excretion is characteristic in both types of involutional osteoporosis in women and therefore seems to be a potential new simple marker of bone resorption. PMID- 8479736 TI - [Ovarian carcinoma antigen (CA 125) and ovarian cancer (clinical follow-up and prognostic studies)]. AB - Serum concentrations of ovarian carcinoma antigen (CA 125) were determined by Abbot CA 125-EIA Monoclonal kit from 66 patients with malignant ovarian tumor. The preoperative serum levels of CA 125 were elevated (> 35.0 IU/ml) in 93% (27/29). After the laparotomy and before the irradiation or chemotherapy in 36% (24/36) of patients had elevated levels. No significant correlation was seen between elevated levels and histology, tumor grade and clinical stage. However, the rate of positive cases were significantly higher in advanced stages than in the 1st stage (p < 0.05). No significant correlation was found between the preoperative levels of CA 125 and the clinical course. The postoperative elevated levels indicated bad prognosis. Good conformity was found between CA 125 levels and the therapy response. Serological follow up revealed a correlation with the clinical course of ovarian carcinoma in 84% (44/52). In patients with tumor progression the CA 125 levels increased before clinical signs of progression with median lead time of 97 days. The second look laparotomy proved, that residual tumor larger than 2 cm of diameter cause elevated levels. Smaller tumors remained marker negatives. CA 125 determination before operation, during and after therapy provide a useful tool in detecting progression and persistence of ovarian carcinoma. PMID- 8479737 TI - Overexpression of cyclin D1 in mouse skin carcinogenesis. AB - Recent studies have provided evidence suggesting that disruption of cyclin function may play a critical role in tumorigenesis. Cyclin D1, a putative G1 cyclin previously isolated in human parathyroid adenomas (designated PRAD1) and mouse macrophages (designated Cyl1), has been implicated in various neoplasias including breast and squamous cell carcinomas (SCC). The role of cyclin altered regulation in the different stages of tumor progression has not been studied in a well defined animal model system. In the study presented here, Cyl1 was mapped to the distal end of mouse chromosome 7 and found to be dramatically overexpressed in skin SCC. In premalignant stages of tumor development, early papillomas showed basal Cyl1 transcript levels, whereas over-expression was observed in most advanced papillomas. These findings suggest that altered expression of cyclin D1 plays a critical role in mouse skin carcinogenesis and may be related to the acquisition of autonomous growth by papillomas. Further studies on the role of cyclin D1 in the mouse model system should prove valuable for understanding the multistep basis of tumor progression. PMID- 8479738 TI - Amino acid substitutions modulate the effect of Jun on transformation, transcriptional activation and DNA replication. AB - The retroviral oncogene v-jun and its cellular counterpart code for proteins that function as major components of the transcription factor complex AP-1. Jun proteins bind to the AP-1 consensus sequence as homodimers or heterodimers with members of the Fos protein family. This report compares the ability of viral and cellular Jun proteins (v-Jun and c-Jun) to activate transcription and to stimulate DNA synthesis. The effect of amino acid substitutions on cellular transformation is also described. In F9 cells c-Jun is a more effective transactivator than v-Jun, which carries two amino acid substitutions in the carboxy-terminal region that together down-regulate transactivation. The delta deletion, present in the amino-terminal region of v-Jun, does not affect transactivation in F9 cells; however, it does modulate the stimulation of DNA synthesis. When delta is deleted, the amino acid substitutions are without consequence on DNA synthesis. In the presence of delta the amino acid substitutions down-regulate DNA synthesis. Deletion of the Jun transactivation domain, which is required for cellular transformation, abolishes both transactivation and stimulation of DNA synthesis. We conclude that transformation, transactivation and stimulation of DNA synthesis all depend on the presence of the transactivation domain. The three functions are, however, not tightly correlated, and further work is needed to define the role of the biochemical activities of Jun in oncogenesis. PMID- 8479739 TI - Mutation of a phosphorylation site in the DNA-binding domain is required for redox-independent transactivation of AP1-dependent genes by v-Jun. AB - The ability of the nuclear oncoprotein Jun to activate transcription is controlled both by level of DNA binding and by the activity of its transactivation domain. Control of DNA binding is achieved by two mechanisms: phosphorylation and redox regulation. Mutation of Ser-226 inhibits phosphorylation of the DNA binding, resulting in enhanced DNA-binding and transactivation activity of Jun. In contrast, mutation of Cys-252, which is the target for repression of DNA-binding activity under oxidative conditions, results in a strong decrease of Jun-specific activation of transcription. However, transactivation by c-Jun-Cys-252 is fully restored upon mutation of Ser-226. Both mutations are also found in the oncogenic counterpart of c-Jun, v-Jun, and are the only differences between these proteins in the DNA-binding domain, suggesting that v-Jun escapes down-modulation of DNA binding by both mechanisms. However, inhibition of phosphorylation of Ser-226 is absolutely required for the ability of v-Jun to activate transcription of AP-1-dependent genes in a redox-independent manner. PMID- 8479740 TI - Chimeric c-Jun containing an heterologous homodimerization domain transforms primary chick embryo fibroblasts. AB - To investigate a possible role for c-Jun homodimers in c-Jun-mediated transformation, we designed two chimeric c-Jun derivatives, called c-Juneb1 and c Jungcn4. In these chimeric derivatives the natural dimerization domain of c-Jun was replaced by the heterologous homodimerization domain of the Epstein-Barr virus EB1 or the yeast GCN4 transcription factor. Chick embryo fibroblasts chronically infected with retroviruses expressing c-Jun, c-Juneb1 or c-Jungcn4 are transformed. Infection with each construction results in sustained growth in low serum and development of colonies from single cells in agar with similar efficiencies. In contrast to c-Jun, c-Juneb1 and c-Jungcn4 confer additional phenotypic alterations related to in vitro transformation including a condensed cell morphology and ability to develop highly invasive, fast growing colonies in agar. These data suggest that c-Jun homodimers can transform chick embryo fibroblasts and activate cellular functions which influence cell morphology and invasive potential in agar. These findings are consistent with the notion that cellular transformation by c-jun is mediated by c-Jun homodimers. PMID- 8479741 TI - Structural determinants outside of the leucine zipper influence the interactions of CREB and ATF-2: interaction of CREB with ATF-2 blocks E1a-ATF-2 complex formation. AB - Dimerization of leucine zipper-containing proteins has been associated characteristically with the formation of a coiled-coil structure between two compatible leucine zipper motifs. In the present study we demonstrate the association of the leucine zipper of cAMP response element-binding protein (CREB) with a zinc finger motif of ATF-2. The association of the CREB leucine zipper with the ATF-2 zinc finger is stabilized if the ATF-2 leucine zipper is intact, implying that the preferred interactive structure of ATF-2 juxtaposes the amino terminal zinc finger motif of this protein with the carboxy-terminal leucine zipper of this same protein. Furthermore, we demonstrate that the association of the CREB leucine zipper with the ATF-2 zinc finger in vitro blocks the association of the adenoviral E1a protein with ATF-2. Similarly, overexpression of full-length CREB, or a truncated version of this protein corresponding to the carboxy-terminal 74 amino acids that make up the DNA-binding and dimerization domains, can block the ATF-2-mediated transcriptional stimulation by E1a in vivo. Mutation of the ATF-2 zinc finger motif stimulates DNA binding of this protein, and abolishes interactions with E1a and CREB proteins. These results demonstrate that the structural conformation of ATF-2 is critical for DNA binding and protein protein interactions and, further, that leucine zippers can mediate protein protein interactions with structural motifs other than leucine zippers. PMID- 8479742 TI - Wild-type but not mutant p53 can repress transcription initiation in vitro by interfering with the binding of basal transcription factors to the TATA motif. AB - It has previously been shown that excess wild type (wt) p53 can repress the transcriptional activity of a variety of promoters in intact cells. To determine whether this transcriptional repression represented a direct effect of p53, wt and mutant p53 were prepared from E. coli-produced p53 and from insect cells infected with a recombinant baculovirus. When added into an in vitro transcription system, wt p53, but not mutant p53 reduced markedly transcription from the c-myc promoter, as well as from an array of other promoters, with the exception of an MHC class I gene promoter. The presence of wt p53 seemed to affect specifically the formation of the transcription preinitiation complex because preformed initiation complexes were completely refractory to wt p53, as was also the process of transcript elongation. Wild-type but not mutant p53 interfered with the stable binding of TBP and TFIIA to the TATA motif, although both wt and mutant p53 could associate in vitro with purified TBP. We propose that upon binding to TBP, wt but not mutant p53 specifically blocks the ability of TBP to engage in interactions required for efficient transcriptional initiation. This may account, at least in part, for the ability of excess wt p53 to inhibit cell proliferation and to interfere with neoplastic processes. PMID- 8479743 TI - A novel germline p53 splicing mutation in a pediatric patient with a second malignant neoplasm. AB - A novel germline p53 splicing mutation was identified in a pediatric patient with two metachronous primary cancers that are constituent tumors of the Li-Fraumeni syndrome. Genomic DNA from the second tumor showed the same mutation and loss of heterozygosity at the p53 locus. The mutant mRNA and protein were present in the tumor tissue. In contrast, in the normal tissues bearing the germline mutation in the heterozygous state, predominantly normal mRNA was expressed and the mutant p53 protein was not detectable. The functional silence and relative lack of mutant p53 mRNA expression in the normal tissues of this patient may be caused by decreased stability or decreased production. If this proves a more general pattern of expression of mutant p53 in individuals with germline mutations, these findings may explain the paucity of tumors in individuals affected with the Li Fraumeni syndrome. PMID- 8479744 TI - Defining the critical gene expression changes associated with expression and suppression of the tumorigenic and metastatic phenotype in Ha-ras-transformed cloned rat embryo fibroblast cells. AB - Carcinogenesis requires a complex series of genetic changes often involving multiple oncogenes and the inactivation of multiple tumor-suppressor genes. We presently examined the effect of the Krev-1 tumor-suppressor gene on the tumorigenic and metastatic potential of Ha-ras-transformed cloned rat embryo fibroblast (CREF) cells. Ha-ras-transformed CREF cells are morphologically transformed and anchorage independent; produce reduced levels of nm23-H1 (a putative metastasis-suppressor gene product) and TIMP-1 (tissue inhibitor of metalloproteinase 1) transcripts and mRNA compared with CREF cells; produce increased levels of cripto, 94-kDa gelatinase/type IV collagenase (94-kDa GEL), osteopontin (OPN) and transin/stromelysin transcripts and mRNA compared with CREF cells; and are tumorigenic and metastatic in both nude mice and syngeneic rats. Ha-ras-transformed CREF cells coexpressing the Krev-1 gene display a reversion in cellular phenotype and gene expression to that of untransformed CREF cells. However, Ha-ras/Krev-1-coexpressing CREF cells retain, albeit with extended latency periods, both tumorigenic and metastatic potential that is not related directly to the final level of Ha-ras or Krev-1 mRNA or the Ha-ras p21 transforming protein. Development of metastatic potential is, however, directly correlated with a reduction in nm23-H1 and TIMP-1 transcription and mRNA levels and an enhanced expression of cripto, 94-kDa GEL, osteopontin and transin. In contrast, expression of additional tumor-suppressor genes, such as the RB gene and p53, or genes associated with tumorigenesis in other model systems, such as major excreted glycoprotein (MEP), 72-kDa gelatinase/type IV collagenase (72-kDa GEL), fibronectin (FIB), tenascin and intracellular adhesion molecule 1 (ICAM-1) is not altered in a consistent manner during in vitro transformation suppression or escape from tumorigenic and metastatic suppression. These results indicate that Krev-1 suppression of the Ha-ras-transformed/oncogenic phenotype is associated with a distinct program of gene expression changes manifested by altered rates of transcription and steady-state mRNA levels of specific oncogenic suppressing and oncogenic-inducing genes. These data support a model of Ha-ras induced metastasis in CREF cells that involves a direct modulation in the expression/suppression of specific combinations of oncogenic-suppressor genes and metastasis-promoting genes that are regulated coordinately in the process of tumor progression. PMID- 8479745 TI - Autocrine transformation of hemopoietic cells resulting from cytokine message stabilization after intracisternal A particle transposition. AB - Cell lines that no longer require exogenous interleukin 3 (IL-3) for growth were isolated from an IL-3-dependent cell line that possesses characteristics of early lymphoid cells. Unlike the parental cells (FL5.12), these autocrine transformed lines (FL-IL3-R) constitutively secreted IL-3, were rearranged at the IL-3 locus and formed tumors upon injection into syngeneic mice. The rearrangement and IL-3 expression resulted from the transposition of an intracisternal A particle (IAP) provirus into the 3' untranslated region of the IL-3 gene. This region contained ATTTA sequence motifs that have been associated with cytokine and oncogene mRNA instability. IL-3 transcripts from the autocrine transformed cell lines had a longer half-life than similar transcripts isolated from either phorbol ester stimulated T cells or the WEHI-3B myelomonocytic cell line. IAP proviral transposition did not alter the transcription rate of the IL-3 gene in FL-IL3-R cells. Therefore, IAP proviral transposition can activate IL-3 gene expression by prolonging mRNA stability, and this mechanism can contribute to the autocrine transformation of the hemopoietic cells. PMID- 8479746 TI - ABL oncogenes directly stimulate two distinct target cells in bone marrow from 5 fluorouracil-treated mice. AB - Mice reconstituted with BCR/ABL-infected 5-fluorouracil-treated bone marrow are considered a model system for human chronic myelogenous leukemia, a malignancy that arises in hematopoietic stem cells. These animals develop multiple types of hematopoietic tumors, which could arise either from undifferentiated cells that mature during tumor development or from progenitors committed to different lineages. To examine the BCR/ABL-sensitive target cells present in the marrow of mice treated with 5-fluorouracil, we used a single-step in vitro assay. These experiments revealed that both the P210 and P185 BCR/ABL proteins and the related v-abl protein induce lymphoid and myeloid colonies, colony types that mimic two of the prominent types of tumors found in the reconstitution model. The lymphoid colonies were similar to lymphoid colonies found following infection of normal bone marrow with respect to differentiation state and tumorigenicity. The cells in the myeloid colonies were differentiated and non-tumorigenic. Fluorescence activated cell sorting revealed that most of the lymphoid and myeloid colonies arose from distinct precursors and that the lymphoid colonies arose from B lineage-committed cells. These data suggest that most of the lymphomas observed in the reconstitution model arise from committed progenitors that are distinct from those involved in the myeloid disease. PMID- 8479747 TI - The physiology of bcl-2 expression in murine B lymphocytes. AB - Quantitation of bcl-2 gene expression in B-lineage lymphocytes from normal adult mice allows the identification of four cell populations, characterized by successive three- to fivefold increases in average mRNA levels: bone marrow pre-B cells, bone marrow B cells, splenic B cells and long-lived splenic B cells. Thus, in line with previous experiments using overexpression systems, a correlation between longevity and levels of bcl-2 mRNA exists also in the physiology of B lineage cells. The data are compatible with a quantitative regulation of expression, possibly determined at selective differentiation steps. No difference in bcl-2 expression was detected by comparing splenic IgD+ with IgD- B cells, while distinctly low levels of bcl-2 mRNA were scored in peritoneal CD5+ and CD5- B cells. These observations indicate that the reported persistence of peritoneal B cells may be controlled by mechanisms other than bcl-2 gene expression. PMID- 8479748 TI - Transfected wild-type and mutant max regulate cell growth and differentiation of murine erythroleukemia cells. AB - Max protein forms specific DNA-binding dimeric complexes with itself and with proteins of the c-myc gene family. A large volume of data has accumulated on the role of the c-myc proto-oncogene in cell proliferation, differentiation and tumorigenesis. To elucidate the role of max in regulating c-myc functions and the effect of both proteins on cell proliferation and differentiation, we transfected murine erythroleukemia (MEL) cells with a full-length wild-type (wt) human max gene and a mutant containing a double point mutation in the basic region (bm), which abolishes specific DNA binding. All clones expressing wt-max grow slowly, and the process of inducer-mediated differentiation is delayed. Furthermore, cells transfected with the mutated max exhibit growth retardation, accumulation in the G0/G1 phase of the cell cycle and spontaneous differentiation. Our findings are consistent with a model in which a large excess of wt-Max in the cells enhances the formation of Max-Max growth-suppressor complexes, while elevated bm-Max deprives the cell of growth-promoting Myc-Max heterodimers in a dominant-negative manner, presumably by inactivating endogenous Myc and Max. PMID- 8479749 TI - Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings. AB - We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benign and malignant tumours (tricholemmoma of the scalp, multiple trichoepitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, malignant fibrous histiocytoma of the thigh and endometrial adenocarcinoma) and belongs to a family with some, but not all, features of the Li-Fraumeni syndrome. The mutation, found in both blood lymphocyte and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early age. We have demonstrated that formalin-preserved material from these tumours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunohistochemical positivity with four antibodies to the p53 protein. Positive staining was also seen in scattered nuclei of morphologically normal epidermal keratinocytes and pilosebaceous cells, but not in lymphocytes or other morphologically normal cells from the index case. However, a similar staining pattern in apparently normal tissue was also observed in 13/48 sections from other individuals with various skin conditions (melanocytic naevi, psoriasis and normal skin adjacent to malignant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p53 mutations. PMID- 8479750 TI - Tumorigenic activity of rho genes from Aplysia californica. AB - rho genes have been found in both lower and higher eucaryotes. They code for proteins of 21 kDa, highly conserved in evolution, which belong to the superfamily of ras GTPases. Among the members of this superfamily there are proteins with a regulatory function, such as ras, and proteins involved in vesicular trafficking, such as the family of rab proteins. We have investigated the putative role of rho proteins from Aplysia californica as transforming GTPases utilizing the wild-type and a Val-14 mutant, equivalent to the oncogenic Val-12 mutation of ras genes found in animal and human tumors. Over-expression of either rho gene was sufficient to confer anchorage- and serum-independent growth. Moreover, when introduced into nude mice, selected clones generated from either gene were able to induce tumors, although those carrying the mutated version were more efficient. Pathological analysis indicated that generated tumors corresponded to well-differentiated fibrosarcomas with distinct and intersecting bundles and spindle cells. By contrast, ras-induced tumors were poorly differentiated fibrosarcomas. Thus, our results indicate that under appropriate conditions rho genes function as oncogenes and may have a role in the regulation of proliferation in fibroblast cells. PMID- 8479751 TI - Lack of c-jun expression in a transformed cell line isolated by glucocorticoid promotion of ras-transfected rat embryo fibroblasts. AB - Rat embryo fibroblasts (REFs) are inefficiently transformed by the T24-ras oncogene. A contributing factor to cellular resistance to transformation is the limited tolerance to p21-ras oncoprotein expression. Here we present data suggesting that long-term glucocorticoid treatment of ras oncogene-transfected REFs results in increased tolerance to p21-ras oncoproteins, leading to expression of the transformed phenotype. Stably transformed cell lines that expressed high levels of H-ras and could be maintained in the absence of hormone were isolated. In three out of four lines studied, the AP-1-dependent collagenase gene was expressed at a low level. In one of these lines, low collagenase expression was paralleled by lack of c-jun mRNA. Immunochemical analysis revealed that progression to hormone independence was not paralleled by mutations in the p53 gene. We propose that a decreased expression of AP-1-driven genes may result in increased tolerance to p21-ras oncoprotein. PMID- 8479752 TI - Expression cDNA cloning of a serine kinase transforming gene. AB - By ectopic expression of cDNAs derived from a Ewing sarcoma cell line in NIH3T3 cells, we isolated a transforming gene (est). Sequence analysis revealed homology to the cot oncogene, which encodes a novel serine kinase. Whereas the cot product was truncated at its carboxy-terminal end as a result of gene rearrangement during transfection, est encodes the normal cot product. Thus, this gene can be activated as an oncogene by overexpression as well as by gene rearrangement. NIH3T3 cells transfected with est formed progressively growing colonies in soft agar and were tumorigenic in nude mice. The 3.2-kb est transcript was expressed at low level in both human fibroblasts and epithelial cells. Addition of the tumor promoter, okadaic acid (OA), or cytokine, interleukin 1 (IL-1), but not serum or platelet-derived growth factor (PDGF), induced increased expression of the est transcript. Using fluorescence in situ hybridization, we localized the est gene to the short arm of human chromosome 10 at band p11.2. PMID- 8479753 TI - The ezrin-like family of tyrosine kinase substrates: receptor-specific pattern of tyrosine phosphorylation and relationship to malignant transformation. AB - A method for the isolation of tyrosine kinases substrates was developed. The method takes advantage of immuno-affinity purification of an entire set of proteins phosphorylated by tyrosine kinases, followed by generation of antisera against the purified protein pool and immunological screening of bacterial expression libraries with these antisera. By applying this methodology to the study of the phosphorylation events triggered by activation of the epidermal growth factor receptors, we have isolated several cDNAs encoding novel putative tyrosine kinase substrates. One of these cDNAs encodes radixin, a protein belonging to the band 4.1 family of proteins and highly related to ezrin and moesin. We demonstrated that, despite a high degree of relatedness, these three proteins exhibit a distinct receptor-specific pattern of phosphorylation, raising the possibility that they might mediate receptor-specific cellular changes. In addition the generation of antibodies specific for either radixin, ezrin or moesin allowed us to show that a previously described tumor transplantation antigen is indeed ezrin, thus implicating this protein in the determination of the biological phenotype of certain tumors. PMID- 8479754 TI - Two potentially oncogenic cyclins, cyclin A and cyclin D1, share common properties of subunit configuration, tyrosine phosphorylation and physical association with the Rb protein. AB - Originally identified as a 'mitotic cyclin', cyclin A exhibits properties of growth factor sensitivity, susceptibility to viral subversion and association with a tumor-suppressor protein, properties which are indicative of an S-phase promoting factor (SPF) as well as a candidate proto-oncogene. Other recent studies have identified human cyclin D1 (PRAD1) as a putative G1 cyclin and candidate proto-oncogene. However, the specific enzymatic activities and, hence, the precise biochemical mechanisms through which cyclins function to govern cell cycle progression remain unresolved. In the present study we have investigated the coordinate interactions between these two potentially oncogenic cyclins, cyclin-dependent protein kinase subunits (cdks) and the Rb tumor-suppressor protein. The distribution of cyclin D isoforms was modulated by serum factors in primary fetal rat lung epithelial cells. Moreover, cyclin D1 was found to be phosphorylated on tyrosine residues in vivo and, like cyclin A, was readily phosphorylated by pp60c-src in vitro. In synchronized human osteosarcoma cells, cyclin D1 is induced in early G1 and becomes associated with p9Ckshs1, a Cdk binding subunit. Immunoprecipitation experiments with human osteosarcoma cells and Ewing's sarcoma cells demonstrated that cyclin D1 is associated with both p34cdc2 and p33cdk2, and that cyclin D1 immune complexes exhibit appreciable histone H1 kinase activity. Immobilized, recombinant cyclins A and D1 were found to associate with cellular proteins in complexes that contain the p105Rb protein. This study identifies several common aspects of cyclin biochemistry, including tyrosine phosphorylation and the potential to interact directly or indirectly with the Rb protein, that may ultimately relate membrane-mediated signaling events to the regulation of gene expression. PMID- 8479755 TI - Analysis of multigene families by DNA fingerprinting of conserved domains: directed cloning of tissue-specific protein tyrosine phosphatases. AB - Little is known about the number of mouse protein tyrosine phosphatases (PTPs) and their developmental and tissue-specific expression patterns. A new procedure based on fingerprinting of amplified catalytic domains detects expression of at least 20 different mouse PTPs during development. The majority of these PTPs show developmentally regulated expression patterns; some display a unique tissue specificity. Diagnostic fragments detected in the fingerprint analysis are used here as specific probes to directly clone two previously unknown ubiquitously expressed PTPs and PTP1C, a protein tyrosine phosphatase highly expressed in thymus RNA. The fingerprinting procedure is also applicable to the analysis of protein tyrosine kinases and may also be used to study the expression pattern of other multigene families. PMID- 8479756 TI - Deletion mapping in colorectal cancer of a putative tumour suppressor gene in 8p22-p21.3. AB - Although previous studies of acquired loss of heterozygosity (LOH) in colorectal tumours have suggested that a tumour suppressor gene may lie within the short arm of chromosome 8, its precise localisation remains to be determined. To obtain a more accurate positional map 120 colorectal cancers were examined with eight chromosome 8 polymorphic markers comprising both restriction fragment length polymorphisms and microsatellite polymorphisms based on (CA)n repeats. 91 cases were informative and LOH was detected in 47 (51%). The markers most commonly sited within the lost region mapped to the lipoprotein lipase gene (LPL) at chromosome 8p22. From study of tumours showing break-points within 8p, a common region of deletion was established extending centromerically from LPL to the ankyrin 1 gene (ANK1) which is mapped to 8p21.1-11.2. This overlaps with common deleted regions observed in other studies of colorectal tumours (8p23.1-p21.3) and bladder tumours (8p21-q11.2). Taken together, the results in colorectal cancer delineate a region in 8p22-p21.3 where the putative tumour suppressor gene must lie. The chromosome 8p deletions appear to be independent of those involving 5q and 17p in the same tumours. No relationship was found between the presence of 8p deletion and site or stage of the tumour, or the sex or age of the patient at diagnosis. PMID- 8479757 TI - Stabilised p53 facilitates aneuploid clonal divergence in colorectal cancer. AB - Mutations in the p53 tumour suppressor gene are amongst the most frequent genetic abnormalities acquired in tumours. Recent studies in vitro suggest that mutant p53 destabilises the genome and facilitates development of aneuploidy. Here, in a study of 83 colorectal carcinomas, we demonstrate that alterations in p53 (detected by immunocytochemical stabilisation) precede and apparently facilitate divergence of aneuploid sub-clones. Aneuploidy in these tumours (but not those with normal p53) is predominantly in the subtetraploid range, suggesting that endoreduplication is important in its origin. This association with a specific phase of carcinoma progression is not shared by other commonly acquired genetic abnormalities in these tumours. These observations highlight the critical role of p53 in the regulation of abnormal chromosome replication and afford an explanation for the association between p53 abnormalities, aneuploidy and biological aggression in cancer. PMID- 8479758 TI - The medical profession: reality and reform. PMID- 8479759 TI - Market economics and biomedical ethics. AB - Though biomedical ethics has only recently been recognized as a major new medical field, the connection between the practice of medical professionals and the ethics of medical practice dates back to the beginning of Western medicine. More recently, ethics has become more and more involved with economics. PMID- 8479760 TI - Assessing the need for bioethics networks. AB - Because the ethical choices of medicine become more and more complex each year, the Pennsylvania Medical Society Commission on Bioethics in 1992 sponsored a survey to assess the need for a statewide ethics network. This article discusses the results of that survey. PMID- 8479762 TI - Student trustee discusses tuition, choices, and reform. PMID- 8479761 TI - Physicians speak out on system reform concerns. AB - Physicians this past winter took an aggressive role testifying at hearings on a health care reform plan proposed late last year by the governor's Economic Development Partnership (EDP). The State Society offered substantial support to those physicians and closely monitored each event. This second in a series of articles highlights Society members' comments about reform and includes excerpted testimonies submitted to the EDP by three concerned physicians. PMID- 8479763 TI - Helping the medically indigent and underserved. Part II--Physician's Voluntary Fee Discount Program and Society-AMA Cooperative Physician Placement Service. PMID- 8479765 TI - New methodology challenges PRO. PMID- 8479764 TI - The intimate plague: child abuse becomes epidemic. Interview by Juli C. McGreevy. PMID- 8479766 TI - Relief offered in underserved areas. The Health Care Group. PMID- 8479767 TI - American ethics: a world perspective. PMID- 8479768 TI - Crossed eyes. PMID- 8479769 TI - [Hepatitis B vaccination of neonates]. PMID- 8479770 TI - [Guidelines for completing a medical certificate for obtaining a higher rate of family assistance in atopic dermatitis]. AB - This paper gives guidelines for medical doctors in which cases of atopic dermatitis an attestation--according to austrian law--can be given to get an elevated family subvention. Following points have to be taken into consideration: correct diagnosis of atopic dermatitis, severity of disease (more than 10% of body surface), duration of disease (more than 6 months), correct treatment with acknowledged methods, necessity of diet and psychotherapy, combination with other atopic diseases. In the rule only in infancy and for preschool aged children the attestation can be given. PMID- 8479771 TI - [Vitamin K administration to neonates]. PMID- 8479772 TI - [Diphtheria in an infant]. AB - A seven week old infant developed pharyngeal diphtheria. The child quickly deteriorated with severe dyspnea and bradycardia. These symptoms made endotracheal intubation necessary. The pharynx and the larynx were covered with pseudomembranes. At the fourth day of hospital stay antitoxin has been administrated. At first the condition of the child became much better. Then progredient paralysis of the diaphragm occurred and led again to intubation. The neurologic complications resolved completely. Diphtheria--above all in an infant- is a rare disease. Our report shows, that it has to be kept in mind to react adequately if necessary. The source of the infection seemed to be visitors from India or Russia. Therefore Diphtheria generally has to be regarded as an "imported disease". PMID- 8479773 TI - Successful extracorporeal lithotripsy of gallbladder stones in a 12 year-old girl. AB - An otherwise healthy 12-year-old girl presented with radiolucent gallstones and colicky pain. After extracorporeal shock wave lithotripsy and oral bile acid treatment she is free of stones and biliary symptoms since 18 months. The treatment options for gallstone disease in this age group are discussed. PMID- 8479774 TI - [Acute reversible liver necrosis after valproate therapy (immunologic hypersensitivity)]. AB - We describe a case of a 9-year-old boy with the severe acute liver injury caused by idiosyncrasy after the administration of valproate. The liver biopsy performed during the first days after the onset of the disease revealed the necrosis of more than 50% of hepatocytes but the injury was almost fully reversible which was well demonstrated by the second biopsy five months later. After five years an evidence for the immunologic idiosyncrasy caused by valproate was still present, which was demonstrated in vitro by blastic transformation of lymphocytes from the patient. The boy is quite healthy and epilepsy is under control of suximide. The family was informed that the boy could be treated with valproate never more. PMID- 8479775 TI - Ventilator dependence and high tetraplegia. PMID- 8479776 TI - Tetraplegics and the justice of resource allocation. PMID- 8479778 TI - Experience with ventilator dependent patients. PMID- 8479777 TI - The French organisation of mechanical ventilation at home for neuromuscular diseases. AB - In this paper there is an outline of the organisation and the results of domiciliary ventilation for patients with neuromuscular diseases where there are serious respiratory problems, in relation to special facilities that have been made available in France. The clinical and economic benefits are stated, in particular concerning the situation in the greater Paris area. PMID- 8479779 TI - Southport experience with domiciliary ventilation. AB - Experience of the Southport Spinal Injuries Centre in reestablishing ventilator dependent patients back in their own homes has confirmed the view that such level of disability need not prevent people from returning to the community and start living again. Convincing the carers in the community and abolishing the traditional boundaries between hospital and community appear to be the fundamental prerequisites. Increased use of advanced assistive technology will enable these disabled people to have more acceptable control of their lives. PMID- 8479780 TI - The Swedish experience in the organisation of domiciliary ventilation for patients with a high spinal cord injury. PMID- 8479781 TI - Implications of focal spinal cord lesions following trauma: evaluation with magnetic resonance imaging. AB - In a series of 15 patients who underwent early and follow up magnetic resonance imaging following spinal cord injury, those with focal spinal cord abnormalities such as cord contusion or haematoma had worse neurological outcomes, and most developed spinal cord cysts, showing as well-defined areas of CSF intensity within the cord on T1 weighted images. Patients with cord oedema initially, had better outcomes, with the development of residual areas of myelomalacia. These observations suggest that patients with focal initial spinal cord abnormalities may have an increased risk of developing posttraumatic spinal cord cysts, which may be associated with the development of delayed neurological deterioration. PMID- 8479782 TI - The development of a spinal injuries unit in Armenia. AB - A severe earthquake in December 1988 in Armenia, resulted in a large number of spinal cord injuries. A rehabilitation facility was urgently established in Yerevan by the Red Cross with volunteers from various countries outside the then Soviet Union. A programme of training of Armenian doctors, nurses and therapists was established, and a new purpose built spinal unit planned. The new unit was opened in August 1992 and should serve as a model for similar units throughout the Commonwealth of Independent States. PMID- 8479783 TI - Arterial oxygen saturation over time and sleep studies in quadriplegic patients. AB - This study evaluated arterial oxygen saturation (SaO2) over time in a randomly selected group of quadriplegic patients to assess whether clinical history prospectively correlated with profiles of oxygen saturation. In 16 stable male quadriplegic patients (C4-T5), we used pulse oximetry to measure SaO2 over a 24 hour period. Measured values of SaO2 were formatted into a cumulative frequency distribution of SaO2 over time. The cumulative SaO2 values from the quadriplegic patients were compared to SaO2 values in a control group of 12 age-matched healthy male subjects. Ten quadriplegic patients had SaO2 profiles comparable to the range observed in healthy subjects. Six quadriplegic patients had SaO2 profiles outside of the normative range. These 6 exhibited cyclic desaturations (> 4%) during periods of behaviorally-defined sleep, suggestive of sleep disordered breathing. During wakefulness, however, their values of SaO2 were within the normative range. With respect to level of injury, age, time after injury, or medication use, there was no difference between the six 'hypoxic' quadriplegic patients and the 10 'normoxic' quadriplegic patients. Five of the 6 hypoxic patients had a positive medical history of snoring and increased daytime sleepiness, as compared to 6 of 10 normoxic patients who gave a similar history. We also performed polysomnographic studies in a subgroup of 7 quadriplegic patients. In this subgroup, sleep-disordered breathing was observed in 3 patients (AHI of 54/53/12 per hour, respectively). We conclude that in quadriplegic patients, in whom there is a low clinical suspicion for sleep-disordered breathing, there can occur significant decreases in SaO2 over time. PMID- 8479784 TI - The dynamics of magnetic resonance findings in patients with a spinal haematoma. AB - In 6 patients with an incomplete transverse section, magnetic resonance (MR) imaging revealed a spinal haematoma. The MR signal intensity changed with the interval between the haemorrhage and the MR investigation. Signal intensities of T1- and T2-weighted images exhibited specific changes with time after the haemorrhage, allowing for a retrospective assessment of the time of onset of the haemorrhage. PMID- 8479785 TI - Pyrexia in hospitalised spinal cord injury patients. AB - To discover the frequency of pyrexia in spinal cord injury (SCI) patients in the Hospital for Medicine of the Locomotor System (HMLS/SARAH), a review study was undertaken. For a period of 3 months, all new episodes of fever were recorded. During the study 221.3 patients/month were observed. The age ranged from 14 to 60 years and time of lesion from 1 to 6,264 days: 85 patients were paraplegia or paraparetic, and 44 tetraplegic or tetraparetic. At the beginning of the study 10.8% of the patients had fever. During follow up, we observed a rate of 33.9 new incidences per 100 patients/month. In 77.3% only one cause was identified, and in 8% no cause could be defined. The commonest causes were urinary tract infection (UTI) (44.3%), and soft tissue infections (11.4%). Frequent causes of fever in the acute stage other than UTI were complications related to the initial trauma and thromboembolic disease (p < 0.05). These results demonstrate the high incidence of fever in patients with SCI, in addition to providing a useful approach for diagnosis and management. PMID- 8479786 TI - Neurological outcome from conservative or surgical treatment of cervical spinal cord injured patients. AB - This is an analysis of the results of treatment of 1761 patients with traumatic injury of cervical spinal cord, admitted to hospital within the first hours or days after injury. Analysis of the results of conservative treatment in 798 patients and of surgical treatment in 963 patients has shown that the results are to a large extent dependent on the method of treatment and when specialist treatment was started. PMID- 8479787 TI - Adhesive capsulitis of the shoulder. AB - Adhesive capsulitis of the shoulder is a relatively common problem that can cause significant functional morbidity in a wide variety of patient populations. Numerous treatment methods have been advocated and are reviewed and summarized in this article. Although several advances have been made in determining the etiology of this disorder, it remains poorly understood and without any definitive treatment algorithm. PMID- 8479788 TI - Developments in diagnosis of the painful total hip replacement. AB - There has been significant improvement in the interpretation of diagnostic tests for the evaluation of the cemented and uncemented symptomatic total hip replacement. Lucent lines around cemented implants have often been found to represent remodeling rather than loosening. Lysis without looseness has been described as a cause of hip pain in both cemented and uncemented hip replacements. Therefore, there are a number of recent developments in diagnosis that must be considered when evaluating the symptomatic cemented or cementless total hip replacement. Some of these developments are reviewed in this paper. Other developments and contemporary algorithms for treatment incorporating these recent data will be presented in next month's issue. PMID- 8479789 TI - The saphenous nerve: an external method for identifying its exit from the adductor canal. AB - The saphenous nerve is the largest and longest branch of the femoral nerve. At its proximal origin, it travels with the femoral artery. The nerve passes lateral to medial in the adductor canal to emerge subcutaneously and supply the medial side of the knee. This investigation analyzes the course of the nerve in 24 lower extremities (12 right, 12 left) and offers a standardized measuring system for externally pinpointing the nerve's exit from the canal. This study may benefit physicians who treat patients with knee pain of obscure etiology. It probably will have direct application to saphenous nerve injection by physicians as part of a pain-management program. PMID- 8479790 TI - Limited femoral endoprosthesis for avascular necrosis of the femoral head. AB - The options for treatment of the young patient with late-stage avascular necrosis of the femoral head are limited. The authors performed a conservative type of femoral hemiarthroplasty on a select group of patients. They chose for the series only patients with Ficat stage III and IV avascular necrosis, particularly those who had an intact acetabulum and femoral-head involvement only. Of 19 procedures followed for an average of 36 months, there were 84% good and excellent results. The authors feel that this operative procedure may have a role in the treatment of this specific group of young patients. PMID- 8479791 TI - Percutaneous screw fixation of intercondylar fracture of the distal humerus. AB - A greenstick intercondylar fracture of the distal humerus occurred in a 13-year old boy. The articular surface of the trochlea was diastased nearly 5 mm. The fracture was reduced and fixed percutaneously using a 4.5-mm cannulated screw from a lateral approach. PMID- 8479792 TI - Subcapital femoral neck fracture following open reduction and internal fixation of an intertrochanteric hip fracture using a sliding screw and side plate. AB - This case report illustrates a subcapital femoral neck fracture following application of a compression screw and side plate to treat an intertrochanteric hip fracture. This is an uncommon complication in the management of intertrochanteric hip fractures. The authors describe steps in this surgical technique that minimize the possibility of this complication. PMID- 8479793 TI - Measuring intramedullary nails. AB - Determining the length of nail needed for intramedullary nailing can sometimes be difficult. This article describes a simple procedure for taking this important measurement. PMID- 8479794 TI - A 35-year-old-man with pain in the metatarsophalangeal joints. Soft-tissue chondroma. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenographic examinations are found on the first two pages. The final clinical and roentgenographic differential diagnoses are presented on the following pages. PMID- 8479795 TI - The novel hydroxynaphthoquinone 566C80 inhibits the development of liver stages of Plasmodium berghei cultured in vitro. AB - The causal prophylactic activity of the novel hydroxynaphthoquinone, 566C80, was assessed against the exo-erythrocytic (EE) stages of Plasmodium berghei cultured in the human hepatoma cell line, HepG2. 566C80 was found to be highly active as an inhibitor of EE development and was more active than the established causal prophylactic pyrimethamine. A 566C80 concentration of 1.85 x 10(-9) M, added 3 h after sporozoite invasion, reduced the numbers of EE forms visible at 48 h by 50 degrees o, while the equivalent concentration of pyrimethamine was 1.95 x 10(-8) M. PMID- 8479796 TI - Common and rare trout parasites in a small landscape system. AB - Brown trout (Salmo trutta) from four lakes within an area of approximately 40 km2 were found to harbour nine helminth species. Crepidostomum metoecus could be classified as core species, while Crepidostomum farionis had an intermediate position. All the others could be classified as satellite species. Salmon (Salmo salar) fingerlings were grown to smolts in an earthpond over the summer. The fingerlings became infected with Crepidostomum spp. which may indicate a superior colonization ability in the core species. The results support the 'rescue effect hypothesis' rather than the 'carrying capacity hypothesis'. PMID- 8479797 TI - In vitro excystation of Cryptosporidium parvum. AB - Protocols for in vitro excystation of oocysts of Cryptosporidium parvum, including different chemical pre-incubation steps, were compared to examine some of the biochemical triggers involved in excystation and to define an in vitro excystation protocol of a reproducibly high efficiency. Pre-incubation steps which increased the permeability of the oocysts were found to enhance excystation dynamics and pre-treatment of oocysts with saliva was found to decrease the permeability and reduce excystation. Although excystation was maximal after incubation for 4 h, sporozoites tended to lyse over this period, and maximum sporozoite recovery occurred after 30 min. The results obtained are discussed in relation to excystation protocols adopted by different research groups and a number of recommendations are given for in vitro excystation of C. parvum oocysts. PMID- 8479798 TI - Aerobic resistance of Trichomonas vaginalis to metronidazole induced in vitro. AB - Aerobic resistance of Trichomonas vaginalis to metronidazole was induced in vitro by anaerobic cultivation of drug-susceptible trichomonads with low concentrations of the drug (2-3 micrograms/ml) for 50 days. Minimal lethal concentrations (MLC) for metronidazole of the resistant derivatives were high in aerobic susceptibility assays (MLC = 216-261.5 micrograms/ml) but low in anaerobic assays (MLC = 4.2-6.3 micrograms/ml), surpassing MLC values of their parent strain approximately 50-fold and 3-fold under aerobiosis and anaerobiosis, respectively. Sensitivity to metronidazole under anaerobic conditions and activity of the hydrogenosomal enzyme pyruvate: ferredoxin oxidoreductase indicated that the resistance was of the aerobic type. Dependence of the resistance manifestation on O2 was further confirmed by susceptibility assays in vitro performed in defined gas mixtures of different oxygen content (1-20%). Five percent concentration of O2 proved to be the threshold required for resistance demonstration and the MLC values further increased with increasing O2 concentrations. The in vitro-induced resistance was also demonstrated in vivo by subcutaneous mouse assay. The dose of metronidazole needed to cure 50% of infected mice (DC50) was 223 mg/kg x 3 for resistant derivative MR-3a but 6.6 mg/kg x 3 only for its drug-susceptible parent strain. The metronidazole-resistant strains developed in this study correspond by their properties to drug-resistant T. vaginalis strains isolated from patients refractory to treatment, and promise to be a useful tool in the study of 5 nitroimidazole aerobic resistance. PMID- 8479799 TI - Population dynamics of Sphaerospora dicentrarchi Sitja-Bobadilla et Alvarez Pellitero, 1992 and S. testicularis Sitja-Bobadilla et Alvarez-Pellitero, 1990 (Myxosporea: Bivalvulida) infections in wild and cultured Mediterranean sea bass (Dicentrarchus labrax L.). AB - The population dynamics of Sphaerospora dicentrarchi and S. testicularis, myxosporean parasites of sea bass (Dicentrarchus labrax), was studied in different groups of cultured and wild fish. S. dicentrarchi prevalence was higher for wild fish (100%) than for cultured ones (70.5%). Infection levels increased with host age and there were no significant sex differences in cultured fish. Among parasitized organs, the gall bladder and intestine registered the highest infection levels in wild and cultured fish. A progressive increase in infection levels of S. testicularis was observed in cultured males during the spawning season in four consecutive periods. The evolution of the percentage of the different parasitic stages is pointed out. The infection seems to be related to water temperature and gonadal maturation. PMID- 8479800 TI - The recruitment of mast cells, exclusively of the mucosal phenotype, into granulomatous lesions caused by the pentastomid parasite Porocephalus crotali: recruitment is irrespective of site. AB - Adults of the porocephalid pentastomid Porocephalus crotali infect the lung of rattlesnake definitive hosts and larvae develop in rat intermediate hosts. In the latter, nymphs encyst within a variety of tissue sites (commonly abdominal fat bodies and lungs) and each becomes the focus of an eosinophilic granuloma. From an early stage in infections, granulomas become increasingly infiltrated by mast cells which, using conventional histology and paired immunofluorescence against mast cell proteases, appear to be exclusively of the mucosal phenotype. Mucosal mast cells are concentrated along the dorsal region of the parasite and in a plug of tissue containing degenerating cuticles within independent granulomas, which is located between its head and tail. ELISAs against the rat mast cell proteases I and II (RMCP I and II), extracted from abdominal fat, lung, spleen, liver and kidney granulomas at various intervals post-infection, reveal a substantially elevated concentration of RMCP II in all lesions. In fat, concentrations increase up to about 100 days post-infection, at which time moulting ceases and inflammatory responses subside. RMCP II was scarcely detectable in matched control tissues. Unlike infections with certain nematode parasites, where enteric mucosal mast cells secrete RMCP II systemically, concentrations of RMCP II in the serum of infected rats were significantly reduced when compared with age-matched uninfected controls. These results confirm that P. crotali can selectively recruit mucosal mast cells to a variety of tissue sites, most of which are non mucosal. Possible mechanisms are discussed. PMID- 8479801 TI - Purification and properties of phosphoenolpyruvate carboxylase from Molinema dessetae (Nematoda: Filarioidea). AB - The presence of phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31), an enzyme at the branchpoint of glycolysis and the Krebs cycle was detected in the Filaria Molinema dessetae. This enzyme has not previously been identified in Helminths, which have so far been found to only possess a phosphoenolpyruvate carboxykinase (EC 4.1.1.32). This enzyme had a level of activity comparable to that of pyruvate kinase, and was relatively less active than enzymes such as malate dehydrogenase or lactate dehydrogenase. We propose here a method of purification of M. dessetae PEP-carboxylase. When purified to electrophoretic homogeneity, the enzyme had a molecular weight of 64 kDa. Kinetic studies indicated that the carboxylation reaction had an optimal pH of 5.8. The enzyme was inhibited by cations such as Fe2+, Zn2+, Cd2+, Cu2+ but required the presence of Mg2+ or Mn2+. The enzyme was thermostable. The apparent Km value of 2.38 mmol for phosphoenolpyruvate for the carboxylation reaction was higher than previously reported values. The Km value for KHCO3 was found to be 1.6 mmol. PEP-carboxylase did not catalyse the reverse reaction. PMID- 8479802 TI - Vaccination of merino lambs against haemonchosis with membrane-associated proteins from the adult parasite. AB - Groups of South African, farm-reared merino lambs about 4 months old were vaccinated with extracts of adult Haemonchus contortus enriched with H11, an integral membrane protein from the parasite's intestinal microvilli, or with proteins soluble in Tween 20. The lambs were challenged with 5000 infective 3rd stage larvae. Compared to the adjuvant-injected controls, lambs vaccinated with 350 micrograms/kg liveweight of the H11-enriched extract showed an 89% reduction in parasite egg production and an 88% reduction in total worm burden at post mortem 35 days post-challenge. The H11-enriched extract contained some protein also present in the Tween 20 extract. Lambs vaccinated with 600 micrograms/kg of protein soluble in Tween 20 showed a 40% reduction in faecal egg counts and 51% reduction in total worm numbers 35 days post-challenge. Animals injected with 20 micrograms/kg of a sub-fraction containing H11 obtained from the H11 extract, showed a 71% reduction in egg output and total worm numbers. PMID- 8479803 TI - Pharmacological profile of the 5-hydroxytryptamine receptor of Fasciola hepatica body wall muscle. AB - 5-HT is a candidate for the excitatory transmitter at the neuromuscular junction in trematodes including Fasciola hepatica. This study has determined the response of a muscle strip preparation from Fasciola hepatica to 5-HT and a range of agonists that distinguish between the vertebrate receptor 5-HT subtypes. 5-HT increased the resting tone and the rhythmic activity of the muscle strip. Of the 19 compounds tested, only 10 had an effect similar to 5-HT and all but 2 of these were tryptamine compounds. 5-HT was more potent than tryptamine whilst 4-OH tryptamine had no effect, suggesting that the response is mediated by a 5-HT rather than a tryptamine receptor. 5-Fluorotryptamine and 5 carboxyamidotryptamine were the most potent agonists. 8-OH-DPAT also mimicked the effect of 5-HT, though less potently. Assuming that these agents elicit their response through a common receptor, this suggests the presence of a 5-HT receptor with similar properties in terms of agonist recognition as the vertebrate 5-HT1 class of receptor involved in controlling Fasciola muscle motility. PMID- 8479804 TI - Effects of qinghaosu (artemisinin) and its derivatives on experimental cutaneous leishmaniasis. AB - We have investigated the effect of qinghaosu (QHS, artemisinin) and its derivatives on Leishmania major replication in vitro and on the disease development in mice infected with L. major. Artemisinin is effective against promastigotes in vitro, with an ED50 (50% effective dose) at 7.5 x 10(-7) M. Both artemisinin and artemether are leishmanicidal for amastigotes in infected murine macrophages in vitro, with ED50 at 3 x 10(-5) M and 3 x 10(-6) M respectively. These compounds have no effect on the viability of macrophages or on the phytohaemaglutinin-induced proliferation of normal spleen cells, even at 10(-4) M. BALB/c mice infected in the footpad with L. major developed significantly smaller lesions and parasite loads when treated with the compounds. Intra-lesion injection of the compounds was the most effective route. The intramuscular and oral routes were also effective; however, intravenous injection with artesunate was not effective. PMID- 8479805 TI - Assessment of monoclonal antibodies to Echinococcus granulosus antigen 5 and antigen B for detection of human hydatid circulating antigens. AB - Four monoclonal antibodies (MAb) to Echinococcus granulosus Antigen 5 (Ag5) and Antigen B (AgB) were assessed in an enzyme-linked immunosorbent assay (ELISA) for detection of circulating antigens (CAg) in sera of human patients with E. granulosus infection. Around 5.5-8% of 200 sera from 42 surgically proven hydatid patients contained detectable CAg by individual MAb. The combined detection rate for CAg, using four MAb, was 19% (38/200). Although hydatid CAg was detected by MAb in at least one serum sample from 21 of 42 patients, some patients remained negative in the assay regardless of the time when serum samples were taken (pre- or post-operatively), or of the continuing presence of hydatid cysts, their location or fertility. In addition, it was observed that the binding capacity of MAb for sheep hydatid cyst fluid antigen (SHCF) was somewhat reduced in the presence of normal human serum. The CAg detection assay would only be useful for assessment of hydatid infection status in patients with detectable CAg in serum samples. PMID- 8479806 TI - Immunocytochemical evidence for the presence of substance P-like peptide in Diphyllobothrium dendriticum. AB - Substance P immunoreactivity (SP-IR) was detected in the nervous system of the gull-tapeworm Diphyllobothrium dendriticum. The distribution of the SP-IR neurons in the plerocercoid differs from that of other peptidergic and aminergic neurons in the worm. As well as occurring in the ganglionic commissure and along the two main nerve cords, SP-IR neurons are located laterally to the main nerve cords but not dorsally or ventrally. The SP-IR neurons have projections extending to the surface. Bipolar SP-IR neurons with processes to the surface also occur in the tip of the scolex. A sensory function for the SP-IR neurons is suggested. PMID- 8479807 TI - Maximum local helminth parasite community richness in British freshwater fish: a test of the colonization time hypothesis. AB - The investigation of Price & Clancy (1983), which demonstrated a significant positive correlation between total helminth species number per host species and geographical range of freshwater fish host species in Britain, was re-examined using a different measure of parasite species richness. Re-calculation of the correlations between the two parameters after controlling for the effect of the composition of the list of fish by excluding, on biological and distributional grounds, 2 species of agnathans and 7 species of introduced teleosts, and for the effect of sampling effort by using helminth richness in the richest component community of each fish species rather than check-list data, reveals no significant relationship between helminth species richness and host range. Habitat and an omnivorous host diet now appear more significant determinants of helminth richness than the accumulation of parasites by predation. The findings provide little support for the interpretation of the relationship between helminth species richness and host range in terms of island biogeographic theory, but do support an alternative explanation in terms of the colonization time hypothesis, i.e. that helminth species richness is related to the time since the fish host arrived in Britain. PMID- 8479808 TI - Gene therapy: possibilities and promise. PMID- 8479809 TI - Plasma fibrinogen and its correlates in children from a biracial community: the Bogalusa Heart Study. AB - Fibrinogen levels were measured in 5- to 17-y-old children (n = 3047; 40% black and 49% female), from a well-defined biracial community. No significant race and sex differences in fibrinogen levels were observed, but levels increased (p < 0.001) with age or sexual maturation in black females. Adjusted for age, fibrinogen concentrations were positively correlated with ponderal index (weight/height3) (0.09-0.22, p < 0.01), triceps skinfold thickness (0.10-0.23, p < 0.05), and subscapular skinfold thickness (0.13-0.24, p < 0.01) in all race-sex groups. Weak correlations were found between fibrinogen level and blood pressure and lipoprotein components for some of the race-sex groups, but these become nonsignificant or minimal after adjustment for ponderal index and skinfolds. A positive correlation (0.12-0.16, p < 0.01) was found between fibrinogen and white blood cell count for Caucasians, which still held after adjustment for ponderal index and skinfolds. In a stepwise regression, ponderal index, white blood cell count, and HDL cholesterol showed an independent association with fibrinogen. PMID- 8479810 TI - Antenatal cocaine exposure produces accelerated surfactant maturation without stimulation of antioxidant enzyme development in the late gestation rat. AB - Antenatal cocaine administration is associated with increases in catecholamines and glucocorticoids and results in fetal hypoxemia, with the speculated potential for increased free radical formation in the fetus. Because of this, we hypothesized that antenatal cocaine exposure would produce not only accelerated pulmonary surfactant maturation, but also stimulation of antioxidant enzyme (AOE) system maturation and the ability to mount a protective AOE response to hyperoxia as well. Seventy-two, 48, and 24 h before delivery at either 20, 21, or 22 d of gestation, pregnant rats received twice daily s.c. injections of cocaine hydrochloride (40 mg/kg) or saline. Off-spring demonstrated growth retardation with significant reduction in body weight at all 3 gestational d studied that persisted to the 5th postnatal d. Serum corticosterone and total catecholamines were elevated from 50 to 200% in cocaine-exposed adult rats and pups. Advanced surfactant development in cocaine-exposed fetal offspring was apparent at d 21 of gestation, with significant increases in lung disaturated phosphatidylcholine content in cocaine (3.94 +/- 0.67 mg/g lung) versus control (3.25 +/- 0.64) offspring (p < 0.01). No increases in AOE maturation were found in cocaine exposed fetuses at all 3 gestational d studied, whereas a significant decrease was demonstrated in glutathione peroxidase activity at d 20 and 22 of gestation in cocaine-exposed fetuses. In addition, cocaine newborns manifested a protective AOE response to hyperoxia of a magnitude similar to that of control newborns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479811 TI - Mitigation of pulmonary oxygen toxicity in rats by intratracheal instillation of polyethylene glycol-conjugated antioxidant enzymes. AB - Hyperoxic lung injury may be mitigated by increasing alveolar epithelial antioxidant activity. We examined whether intratracheal instillation of superoxide dismutase (SOD) and catalase, conjugated to polyethylene glycol (PEG) to permit cellular access, reduces hyperoxic lung injury. Adult rats, pretreated intratracheally with 1,500 U PEG-SOD and 10,000 U PEG-catalase or with inactivated PEG-SOD/catalase, 1% PEG, or saline (treated controls), were exposed to hyperoxia (fraction of inspired oxygen > 0.95) for 48 h and compared with untreated air controls. Alveolar wash protein values in the treated control groups were significantly higher than in the PEG-SOD/catalase and air control groups, which had comparable values. Lung homogenate and alveolar type II cell SOD and catalase activities were higher after PEG-SOD/catalase treatment and lower after the control treatments when compared with untreated air controls. Lung homogenate dipalmitoyl phosphatidylcholine decreased and alveolar wash dipalmitoyl phosphatidylcholine increased after hyperoxia, but these changes were less after PEG-SOD/catalase treatment. Rats pretreated intratracheally with PEG SOD/catalase survived significantly longer in hyperoxia than saline controls. These data indicate the potential of intratracheal antioxidant treatment to reduce pulmonary oxygen toxicity. PMID- 8479812 TI - Prevention of postasphyxial increase in lipid peroxides and retinal function deterioration in the newborn pig by inhibition of cyclooxygenase activity and free radical generation. AB - Free radicals have been implicated in the development of injury to the immature retina. Asphyxia increases free radicals as well as prostaglandins (PG) in neural tissues. We assessed whether in the retina the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, which in turn disrupts retinal function. Newborn pigs were treated with either saline, ibuprofen (194 mumol/kg i.v.), or allopurinol (1 mmol/kg i.v.), and retinal malondialdehyde (MDA), hydroperoxides, PGE2 and PGF2 alpha levels, and the amplitudes and implicit times of the a- and b-waves of the full-field electroretinogram were measured before and 1 h after a 5-min period of asphyxia. In saline-treated animals, asphyxia caused a marked increase (p < 0.01) in MDA, hydroperoxides, PGE2, and PGF2 alpha concentrations in the retina. This was associated with a significant decrease (p < 0.01) in the b-wave amplitude measured under scotopic and photopic conditions and an increase in the b-wave implicit times. Ibuprofen and another cyclooxygenase inhibitor, indomethacin (28 mumol/kg i.v.), decreased PGE2 and PGF2 alpha levels and prevented the increase in MDA and hydroperoxides after asphyxia. Allopurinol maintained low concentrations of MDA and hydroperoxides after asphyxia. Both ibuprofen and allopurinol prevented the postasphyxial changes in the b-wave amplitude and diminished the delay in implicit time observed after asphyxia in saline-treated pigs. Our findings suggest that in the retina after asphyxia free radicals appear to originate primarily from the cyclooxygenase pathway and contribute to the deterioration in retinal electrophysiologic function of the newborn animal. Cyclooxygenase inhibitors, like free radical scavengers, may protect retinal function from deteriorating after oxidative stresses. PMID- 8479813 TI - Hyperoxia and alkalosis produce pulmonary vasodilation independent of endothelium derived nitric oxide in newborn lambs. AB - Supplemental oxygen and alkalosis are the most effective treatments used to lower pulmonary arterial pressure in children with pulmonary hypertensive disorders. However, their mechanisms of action are unknown. Endothelium-derived nitric oxide (EDNO) is an important mediator of pulmonary vascular tone and produces potent pulmonary vasodilation during pulmonary hypertension. In vitro evidence suggests that EDNO may mediate the vasodilating effects of oxygen. To investigate whether EDNO synthesis mediates the pulmonary vasodilation produced by hyperoxia [normocarbic ventilation with 100% oxygen, arterial oxygen tension > 450 torr (60 kPa)] or alkalosis (hyperventilation with 21% oxygen, pH > 7.55) in vivo, eight intact newborn lambs were studied during similar degrees of pulmonary hypertension induced either by the infusion of U46619 (a thromboxane A2 mimic) or N omega-nitro-L-arginine (an inhibitor of EDNO synthesis). The lambs were sedated, paralyzed, and mechanically ventilated. Meclofenamic acid was infused to inhibit prostaglandin synthesis. During pulmonary hypertension induced by U46619, pulmonary arterial pressure and pulmonary vascular resistance were significantly decreased by acetylcholine (an EDNO-dependent vasodilator) (23.1 +/- 3.4% and 43.3 +/- 14.5%, respectively), hyperoxia (26.8 +/- 7.8% and 32.9 +/- 10.6%), and alkalosis (32.1 +/- 10.3% and 36.1 +/- 17.0%) (p < 0.05). During pulmonary hypertension induced by N omega-nitro-L-arginine, the decreases in pulmonary arterial pressure and pulmonary vascular resistance produced by acetylcholine (9.6 +/- 6.4% and 23.9 +/- 14.1%, respectively) were significantly attenuated (p < 0.05), but the decreases produced by hyperoxia or alkalosis were unchanged. Therefore, hyperoxia and alkalosis can produce pulmonary vasodilation independent of EDNO synthesis in the intact newborn lamb. PMID- 8479814 TI - Biologic effects of parenteral bisulfite on human vascular tissue. AB - Antioxidant properties of bisulfite are used to stabilize parenteral amino acid solutions. After reports of adverse reactions to dietary sulfites, we evaluated whether the infusion of bisulfite had biologic effects on human vascular tissue. Because an endothelial oxidative injury can affect mediators of vasoreactivity, vascular pressure and prostaglandin production were studied in an intact human vein model infused with clinically relevant amino acid solutions differing only by their metabisulfite content (0 versus 300 mg/L). The amino acid solution containing bisulfite presented higher venous pressure (p < 0.01) and prostaglandin production (6-keto-prostaglandin F1 alpha, p < 0.01; and prostaglandin E2, p < 0.05). A hydroxyl radical-generating system added to the solutions did not modify the pressure readings, but it resulted in an overall decrease in prostacyclin production (p < 0.05). Despite this known inhibitory effect on oxidative challenge on prostaglandin I2 production, prostaglandins remained higher in the presence of bisulfite. The results suggest that the effect of bisulfite takes place before prostaglandin H2 synthesis in the eicosanoid cascade, whereas the oxidative challenge affects specifically the synthesis of prostaglandin I2, after prostaglandin H2, indicating that there is no interaction between bisulfite and the hydroxyl generating system. Bisulfite has local vascular effects on endothelial mediators, separate from its antioxidant properties. PMID- 8479815 TI - Regulation of fetal lamb ductus arteriosus smooth muscle cell migration by indomethacin and dexamethasone. AB - Postnatal closure of the ductus arteriosus (DA) requires the development, during late gestation, of "intimal cushions." These structures, which partially occlude the vessel lumen, are characterized by smooth muscle cell (SMC) migration into an expanded subendothelium. DA SMC migration is dependent upon increased fibronectin (FN) production. We hypothesized that indomethacin (INDO) or dexamethasone, which could influence FN production, may affect SMC migration and DA intimal cushion formation. SMC harvested from the DA and aorta of 100-d fetal lambs were seeded onto three-dimensional collagen gels. Migration into the gels was quantitatively assessed by phase-contrast microscopy. INDO retarded DA SMC migration (p < 0.05), but it had no effect on aorta SMC migration. Synthesis of FN was measured after [35S]-methionine radiolabeling of cells, gelatin sepharose extraction of conditioned media, and resolution by SDS-PAGE. Despite the decrease in migration, INDO did not affect FN synthesis in DA SMC, whereas dexamethasone, a stabilizer of FN mRNA that increased DA FN synthesis by 44%, had no further effect on SMC migration. We then investigated whether INDO might be influencing SMC migration by decreasing collagenase production or altering cell shape through changes in F actin polymerization. Collagenase activity, assessed by zymography using collagen types I and IV, was similar in control and treated DA and aorta cells. Image analysis of the actin cytoskeleton after rhodamine-phalloidin staining of DA SMC, however, revealed significant shortening of INDO-treated DA SMC relative to control, consistent with the observed reduction in migration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479816 TI - Mechanically increased right ventricular afterload alters left ventricular configuration, not contractility, in neonatal lambs. AB - Left ventricular dysfunction has been observed in human infants with pulmonary hypertension. The purpose of this study was to establish whether mechanically increased right ventricular afterload alters left ventricular performance by altering its contractility, configuration, or both. Six neonatal 3- to 7-d-old lambs were acutely instrumented with micromanometer-tipped catheters and two pairs of ultrasonic crystals to measure left ventricular pressure and anterior posterior and septal-free wall dimensions. The product of these two dimensions, denoted left ventricular area, was used as an index of left ventricular volume. Two levels of mechanically increased right ventricular afterload were induced with a closed pericardium under three levels of left ventricular preload produced by whole-blood transfusions. Four brief increases in left ventricular afterload were induced by constricting the aorta under each right ventricular afterload and preload condition. Using multiple linear regression, we found that the slope of the end-systolic pressure-area relationship, an index of contractility, was unchanged [0.90 +/- 0.11 mm Hg/mm2 (SEM)], and stroke area (65.8 +/- 7 mm2) and cardiac output (the product of stroke area and heart rate) (13,400 +/- 1,660 mm2/min) were maintained. However, the area intercept of the pressure-area line at zero pressure (499 +/- 13 mm2) shifted significantly to the left in the presence of both levels of increased right ventricular afterload (by -39.2 +/- 13 and -76.2 +/- 15 mm2, respectively). Mechanically increased right ventricular afterload alters left ventricular configuration and causes a shift in the operating volume (area) range of the ventricle with no change in contractility in 3- to 7-d-old lambs. PMID- 8479817 TI - Pancuronium does not alter the hemodynamic status of piglets after normoxia or hypoxia. AB - Pancuronium is a neuromuscular blocking agent commonly used to eliminate agitation in sick newborn infants requiring mechanical ventilation. Experimental data supporting this method of intervention are controversial, and hemodynamic studies in newborn infants report conflicting results. This study was designed to determine the hemodynamic effects of pancuronium administered under conditions of normoxia, hypoxia, and preexposure to hypoxia in neonatal piglets with normal lungs. After baseline hemodynamic and blood gas measurements were obtained, pancuronium was administered in two i.v. bolus injections of 0.1 mg/kg. Tidal volume and minute ventilation were maintained constant during the experimental procedure by adjusting ventilator settings. Twenty min after pancuronium, no changes from baseline values were found in arterial blood gases, heart rate, cardiac output, mean arterial pressure, systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, central venous pressure, or pulmonary capillary wedge pressure in any of the three conditions studied. In conclusion, pancuronium administered during normoxia, hypoxia, or after preexposure to hypoxia while controlled ventilation is maintained does not alter systemic or pulmonary hemodynamic status of the newborn piglet. PMID- 8479818 TI - Three different strains of heat-killed group B beta-hemolytic streptococcus cause different pulmonary and systemic hemodynamic responses in conscious neonatal lambs. AB - Although group B beta-hemolytic streptococcus (GBS) causes pathologic hemodynamic alterations in both human neonates and neonatal animal models of sepsis, little is known about strain-dependent differences in hemodynamic responses to GBS. This study compared pulmonary and systemic hemodynamic dose-response profiles in conscious neonatal lambs with three different strains of heat-killed GBS originally isolated from infected human neonates (group 1: serotype Ib, early onset sepsis; group 2: serotype Ib, necrotizing enterocolitis; and group 3: serotype III, meningitis). Regression models of hemodynamic responses were characterized after lambs were injected with heat-killed GBS (dose range 0.1-6.0 x 10(9) colony-forming units, i.v.). All three GBS strains caused dose-dependent increases in mean pulmonary arterial pressure and pulmonary and systemic vascular resistances and decreases in cardiac output and heart rate. The GBS strain used in group 1 caused a greater effect on mean pulmonary arterial pressure and systemic vascular resistance than those used in groups 2 and 3 and was the only strain to cause an increase in mean systemic arterial pressure. The GBS strains used in groups 1 and 2 had a greater effect on pulmonary vascular resistance than that used in group 3. No group differences were observed in cardiac output and heart rate responses, which were, however, influenced by age, gender, and duration of postoperative recovery of the lambs. No attenuation or augmentation of hemodynamic effect was observed after sequential doses of 10(9) colony-forming units of GBS given in a single day. This study demonstrates strain-dependent quantitative differences in pulmonary vascular response and qualitative differences in systemic vascular response to heat-killed GBS. PMID- 8479819 TI - Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma levels in neonatal sepsis. AB - Tumor necrosis factor-alpha, IL-1 beta, and IL-6 are thought to be involved in the pathogenesis of sepsis with gram-negative bacteria. We studied these cytokines during neonatal sepsis with mainly gram-positive bacteria. Ten newborns with clinical sepsis and 22 healthy controls were enrolled in the study. TNF alpha plasma levels proved to be increased in the newborns with sepsis up to 560 +/- 234 pg/mL (ng/L) versus 36 +/- 4 pg/mL (ng/L) in the control group (p < 0.005), whereas IL-6 plasma levels in newborns with sepsis were 79.700 +/- 37.500 pg/mL (ng/L) versus 55 +/- 28 pg/mL (ng/L) in the control group (p < 0.01). The IL-1 beta plasma levels were only slightly elevated in the group newborns with sepsis [up to 18 +/- 5 pg/mL (ng/L) versus 7 +/- 1 pg/mL (ng/L) in the control group (p < 0.01)]. After the start of therapy with antibiotics, both TNF alpha and IL-6 plasma levels decreased concomitantly with the improvement of the clinical situation within 2 d. These data confirm the abundant presence of TNF alpha and IL-6 during neonatal sepsis, whereas IL-1 beta appeared to be present in small amounts only. Nevertheless, the IL-1 beta but not the TNF alpha plasma level appeared to correlate inversely with the decrease in diastolic tension as standardized according to birth weight (R = 0.66, p = 0.04). TNF alpha, IL-1 beta, and IL-6 were not correlated with any febrile response in the group with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479820 TI - Combination macrophage-colony stimulating factor and interferon-gamma administration ameliorates the osteopetrotic condition in microphthalmic (mi/mi) mice. AB - Malignant osteopetrosis is a fatal congenital bone disorder characterized by defective osteoclastic function. Death frequently occurs within the first decade of life. The precise molecular defect(s) that causes osteopetrosis is not known. The possibility that osteoclasts, like macrophages, are controlled by interactions with cytokines suggests that these agents may provide a means of increasing osteoclastic function. Macrophage-colony stimulating factor (M-CSF), a cytokine known to enhance macrophage and osteoclast generation, and recombinant human interferon-gamma (rIFN), a cytokine known to stimulate superoxide generation by white cells, were administered to microphthalmic (mi/mi) mice in an attempt to improve the osteopetrotic condition. Each cytokine was administered separately and in combination to neonatal mi/mi mice for 7 consecutive d. Bone turnover, osteoclast numbers, superoxide generation by white cells, and hematocrit were assessed. rIFN, M-CSF, and a combination of the cytokines stimulates oxygen-derived free radical production by white cells and increased bone resorption. rIFN resulted in a reduction in the number of osteoclasts. This reduction in number was ameliorated by M-CSF. M-CSF alone and in combination with rIFN resulted in improved hematopoietic function, increased weight gain, and increased physical activity of the affected mutants. PMID- 8479821 TI - Different regulation of clonal growth by transforming growth factor-beta 1 in human fetal articular and costal chondrocytes. AB - The variable affection of rib and limb growth in human skeletal dysplasias suggests the presence of site-specific regulatory mechanisms for chondrocyte proliferation. We therefore studied the clonal growth of normal human costal and articular chondrocytes from the same four fetuses (15 to 30 wk of gestation) in a semisolid medium (0.8% methylcellulose) with a basal supplementation of 5% heat inactivated FCS. IGF-I[0.3-12.5 ng/mL (0.04-1.6 nmol/L)], IGF-II [0.3-12.5 ng/mL (0.04-1.7 nmol/L)], and hGH [0.5-25 ng/mL (0.02-1.1 nmol/L)] stimulated clonal growth of articular and costal chondrocytes without site-specific difference. In contrast, a significant difference was found for transforming growth factor-beta 1, which proved to be a potent growth factor for fetal articular chondrocytes but did not stimulate or only minimally stimulated fetal costal chondrocytes [p < 0.05 for 0.3 ng/mL (0.01 nmol/L) TGF-beta 1 and p < 0.01 for 1.25 ng/mL (0.05 nmol/L) TGF-beta 1 using paired t test]. Preincubation with an IGF-I receptor antibody (alpha IR-3) completely prevented the proliferative effect of IGF-I, IGF II, and hGH, indicating that hGH acts via autocrine or paracrine induction of IGF. The antibody partly reduced TGF-beta 1 action on articular chondrocytes [p < 0.05 for 0.3 ng/mL (0.01 nmol/L) TGF-beta 1, NS for 1.25 ng/mL (0.05 nmol/L) TGF beta 1 using paired t test]. These results indicate that TGF-beta 1 is involved in the regulation of human fetal growth and has a different effect in ribs and limbs. PMID- 8479822 TI - Effects of ischemia and reperfusion on intrinsic vascular regulation in the postnatal intestinal circulation. AB - The purpose of these experiments was to determine the effect of 1 h of total ischemia followed by 2 h of reperfusion on intrinsic vascular regulation within intestine from 3- and 35-d-old swine. Intrinsic vascular regulation was defined as the ability of in vitro segments of small intestine to bring about adjustments of blood flow and the arteriovenous O2 content difference across the intestinal segment of sufficient magnitude to preserve tissue O2 uptake in response to a 35% reduction in arterial perfusion pressure. This response was elicited before (control conditions) and after ischemia-reperfusion (post-I/R). In older subjects, the efficacy of blood flow regulation was attenuated post-I/R, insofar as blood flow fell in response to pressure reduction. However, this group demonstrated a rise in arteriovenous content difference after pressure reduction under control and post-I/R conditions that were of sufficient magnitude to preserve tissue O2 uptake. In younger subjects, blood flow regulation was absent under control conditions and post-I/R. The arteriovenous O2 content difference increased in response to pressure reduction under control conditions but failed to do so post-I/R; consequently, tissue oxygenation decreased in response to arterial pressure reduction post-I/R in 3-d-old intestine. We conclude that ischemia-reperfusion affects intrinsic vascular regulation in postnatal intestine and that this effect is age-dependent. Intestine from older subjects maintains the intrinsic capacity to preserve tissue oxygenation in response to a hypotensive challenge despite the insult of ischemia-reperfusion, whereas intestine from younger subjects does not maintain this capacity. PMID- 8479823 TI - Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats. AB - We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8% O2). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 microM. Allopurinol did not lower rectal temperature more than 0.04 degrees C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats. PMID- 8479824 TI - Deficiency of the adenine nucleotide translocator in muscle of a patient with myopathy and lactic acidosis: a new mitochondrial defect. AB - In a patient with a mitochondrial myopathy, presenting with lactic acidosis, 31P nuclear magnetic resonance spectroscopy in resting muscle showed half the creatine phosphate level of controls. The creatine phosphate resynthesis rate after aerobic exercise was only 18% of that in controls. However, the activities of complexes I to V catalyzing oxidative phosphorylation and the pyruvate and the 2-oxoglutarate dehydrogenase complexes showed a 2- to 20-fold increase. In line with this, the uncoupled mitochondrial respiration rate was significantly higher than in controls. In contrast, the respiration of the mitochondria from the patient was less stimulated by ADP than that of control mitochondria. This finding could point to a defect in complex V, the enzyme directly involved in ATP synthesis. The activity of complex V, measured as the mitochondrial ATPase activity, and its concentration, as judged from Western blots using antisera against the F1 part of complex V, were, however, also greatly increased in the patient. Alternatively, the transport system, importing ADP into and exporting ATP out of the mitochondrial matrix, the ADP/ATP or adenine nucleotide translocator, could be affected. Immunostaining of Western blots revealed a 4 fold decrease in the concentration of the adenine nucleotide translocator in the patient. Because oxidative phosphorylation was not disturbed in fibroblasts and lymphocytes, we conclude that this patient suffers from a muscle-specific deficiency of his mitochondrial adenine nucleotide translocator, a defect unknown so far. PMID- 8479825 TI - Preservation of permeability barrier ontogenesis in the intrauterine growth retarded fetal rat. AB - The epidermal permeability barrier is provided by intercellular lipids forming multiple membrane bilayers in the stratum corneum. In the fetal rat, the barrier to transepidermal water loss forms during the 20th d of gestation and is accompanied by 1) increasing stratum corneum thickness; 2) increasing stratum corneum lipid content, particularly nonpolar ceramide and cholesterol content; and 3) the formation of lamellar unit structures throughout the stratum corneum interstices. In this report, we demonstrate that among pups of 20 d gestational age increasing barrier competence is correlated with increasing fetal weight. It has been previously demonstrated that fetal rats subjected to intrauterine growth retardation (IUGR) exhibit a thinner stratum corneum and decreased content of differentiation-specific epidermal structural proteins. To determine whether IUGR fetal rats also exhibit immaturity of barrier function and the barrier membrane system, maternal rats underwent unilateral uterine vessel ligation on d 17 or 18 of gestation and IUGR and control littermates were harvested on d 20, 21, or 22 of gestation for determination of transepidermal water loss. Despite significant somatic growth retardation and a thinner stratum corneum, barrier function in IUGR fetal rats did not significantly differ from that in control littermates at any gestational age. In both IUGR and control fetal rat epidermis at 21 d gestational age, lipids were deposited in a membrane pattern as visualized by nile red fluorescence microscopy and formed lamellar unit membrane structures throughout the stratum corneum intercellular domains as observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479826 TI - Erythrocyte docosahexaenoic acid correlates with the visual response of healthy, term infants. AB - Recent studies have reported that formula-fed preterm infants score lower on visual and developmental tests relative to breast-fed preterm infants. This phenomenon has been associated with the presence of docosahexaenoic acid (DHA), an omega-3 fatty acid, in breast milk and its absence from infant formula. To investigate the possibility that DHA status of healthy, term infants is also related to neuronal function of the visual pathway, we studied the erythrocyte fatty acid profiles of 16 infants at 22.3 +/- 3.9 wk of age and related these to maturity of the visual pathway as assessed by visual-evoked potentials. Healthy, term infants fed breast milk had better visual-evoked potential acuity (p < 0.05) and higher DHA levels (p < 0.001) than infants who received infant formula as their major energy source. There was a positive correlation between erythrocyte DHA and visual-evoked potential acuity (p < 0.01). The data are preliminary and the long-term effects as yet unknown. However, our results suggest that there is an urgent need to evaluate the dietary fatty acid supply of formula-fed term infants. PMID- 8479827 TI - Lawson Wilkins Pediatric Endocrine Society and European Society for Paediatric Endocrinology. Fourth Joint Meeting. June 3-7, 1993, San Francisco, California. Abstracts. PMID- 8479828 TI - Ethnocultural variations in the prevalence and impact of childhood chronic conditions. PMID- 8479830 TI - Multiculturalism, chronic illness, and disability. AB - To gain at least an initial understanding of the underlying beliefs and attitudes in a cross-cultural situation, we believe that the three key points discussed in this paper should prove a significant point of departure: 1. Traditional beliefs about the cause of chronic illness or disability will play a significant role in determining family and community attitudes toward individuals with a disability and will influence when, how, and why medical input is sought. 2. The expectation of survival on the part of parents and community will have an effect on the amount of time, energy, and cooperation shown by family and community for the individual who has an impairment. 3. The expectations by family and community for the social role(s) and individual with a chronic illness or disability will hold will affect a broad range of issues, including education, social integration, and independence. Furthermore, although chronic illness and disability are often considered as issues distinct from the full range of problems encountered in society for immigrant and minority groups, in fact, these issues could not be more closely tied. The frequently discussed concerns within the ethnic and minority community about the role of the family, integration and acculturation, social articulation with the greater American society, stress, cross-cultural misunderstanding, and outright prejudice can all compound the problems encountered for the chronically ill or disabled individual in a multicultural society. PMID- 8479829 TI - Health insurance differentials among minority children with chronic conditions and the role of federal agencies and private foundations in improving financial access. PMID- 8479831 TI - Culture, ethnicity, and bicultural competence: implications for children with chronic illness and disability. PMID- 8479832 TI - Culture, ethnicity, and the family: critical factors in childhood chronic illnesses and disabilities. PMID- 8479834 TI - German Physiology Society, 72nd meeting. Munchen, 9-12 March 1993. Abstracts. PMID- 8479833 TI - Race and ethnicity: issues for adolescents with chronic illnesses and disabilities. An annotated bibliography. PMID- 8479835 TI - Address of President Clara D. Noyes. Twentieth annual convention of the NLNE, 1914, St. Louis, Missouri. PMID- 8479836 TI - Address of President Clara D. Noyes. Proceedings of the twenty-first annual convention of the NLNE, 1915, San Francisco, California. PMID- 8479837 TI - Address of President Clara D. Noyes. Proceedings of the twenty-second annual convention of the NLNE, 1916, New Orleans, Louisiana. PMID- 8479838 TI - Address of President Sara E. Parsons. Proceedings of the twenty-third annual convention of the NLNE, 1917, Philadelphia, Pennsylvania. PMID- 8479839 TI - Address of President S. Lillian Clayton. Proceedings of the twenty-fourth annual convention of the NLNE, 1918, Cleveland, Ohio. PMID- 8479840 TI - Address of President S. Lillian Clayton. Proceedings of the twenty-fifth annual convention of the NLNE, 1919, Chicago, Illinois. PMID- 8479841 TI - Address of President S. Lillian Clayton. Proceedings of the twenty-sixth annual convention of the NLNE, 1920, Atlanta, Georgia. PMID- 8479842 TI - Address of President Anna C. Jamme. Proceedings of the twenty-seventh annual convention of the NLNE, 1921, Kansas City, Missouri. PMID- 8479843 TI - Address of President Anna C. Jamme. Proceedings of the twenty-eighth annual convention of the NLNE, 1922, Seattle, Washington. PMID- 8479844 TI - Address of President Linda Richards. Second annual convention of the Superintendents' Society, 1895, Boston, Massachusetts. PMID- 8479845 TI - Address of President Laura Logan. Proceedings of the twenty-ninth annual convention of the NLNE, 1923, Swamscott, Massachusetts. PMID- 8479846 TI - Address of President Laura Logan. Proceedings of the Thirtieth annual convention of the NLNE, 1924, Detroit, Michigan. PMID- 8479847 TI - Address of President Laura Logan. Proceedings of the thirty-first annual convention of the NLNE, 1925, Minneapolis, Minnesota. PMID- 8479848 TI - Address of President Carrie M. Hall. Proceedings of the thirty-second annual convention of the NLNE, 1926, Atlantic City, New Jersey. PMID- 8479849 TI - Address of President Carrie M. Hall. Proceedings of the thirty-third annual convention of the NLNE, 1927, San Francisco, California. PMID- 8479850 TI - Address of Mary E. P. Davis. Third annual convention of the Superintendents' Society, 1896, Philadelphia, Pennsylvania. PMID- 8479851 TI - Address of President Carrie M. Hall. Proceedings of the thirty-fourth annual convention of the NLNE, 1928, Louisville, Kentucky. PMID- 8479852 TI - Toward economic stability, 1929-1944. PMID- 8479853 TI - Address of President Elizabeth C. Burgess. Proceedings of the thirty-fifth annual convention of the NLNE, 1929, Atlantic City, New Jersey. PMID- 8479854 TI - Address of President Elizabeth C. Burgess. Proceedings of the thirty-sixth annual convention of the NLNE, 1930, Milwaukee, Wisconsin.Developing potential leaders. PMID- 8479855 TI - Address of President Elizabeth C. Burgess. Proceedings of the thirty-seventh annual convention of the NLNE, 1931, Atlanta, Georgia. The effect on nursing education of American traditions and ideals. PMID- 8479856 TI - Address of President M. Adelaide Nutting. Fourth annual convention of the Superintendents' Society, 1897, Baltimore, Maryland. PMID- 8479857 TI - Address of President Elizabeth C. Burgess. Proceedings of the thirty-eighth annual convention of the NLNE, 1932, San Antonio, Texas. What are nurses going to do about it? PMID- 8479858 TI - Address of President Effie J. Taylor. Proceedings of the thirty-ninth annual convention of the NLNE, 1933, Chicago, Illinois. Yesterday--today--tomorrow. PMID- 8479859 TI - Address of President Effie J. Taylor. Proceedings of the fortieth annual convention of the NLNE, 1934, Washington, D.C. Of what is the nature of nursing? PMID- 8479860 TI - Address of President Effie J. Taylor. Proceeding of the forty-first annual convention of the NLNE, 1935, New York, New York. Twenty-five years in nursing education. PMID- 8479861 TI - Address of President Effie J. Taylor. Proceedings of the forty-second annual convention of the NLNE, 1936, Los Angeles, California. PMID- 8479862 TI - Toward social reform, 1894-1913. PMID- 8479863 TI - Address of President Nellie X. Hawkinson. Proceedings of the forty-third annual convention of the NLNE, 1937, Boston, Massachusetts.A task and a vision is joy unspeakable. PMID- 8479864 TI - Address of President Nellie X. Hawkinson. Proceedings of the forty-fourth annual convention of the NLNE, 1938, Kansas City, Missouri. The outlook in nursing education. PMID- 8479865 TI - Address of President Nellie X. Hawkinson. Proceedings of the forty-fifth annual convention of the NLNE, 1939, New Orleans, Louisiana. PMID- 8479866 TI - Address of President Nellie X. Hawkinson. Proceedings of the forty-sixth annual convention of the NLNE, 1940, Philadelphia, Pennsylvania. PMID- 8479867 TI - Address of President Stella Goostray. Proceedings of the forty-seventh annual convention of the NLNE, 1941, Detroit, Michigan. PMID- 8479868 TI - Address of President Stella Goostray. Proceedings of the forty-eighth annual convention of the NLNE, 1942, Chicago, Illinois. PMID- 8479869 TI - Address of President Mary Agnes Snively. Fifth annual convention of the Superintendents' Society, 1898, Toronto, Canada. PMID- 8479870 TI - Address of President Stella Goostray. Proceedings of the forty-ninth annual convention of the NLNE, 1943, Chicago, Illinois. PMID- 8479871 TI - Address of President Stella Goostray. Fiftieth annual report of the NLNE, 1944, Buffalo, New York. The time is now. PMID- 8479872 TI - Toward professional maturity, 1945-1952. PMID- 8479873 TI - Address of President Ruth Sleeper. Fifty-first annual report of the NLNE, 1945, New York, New York. PMID- 8479874 TI - Address of President Ruth Sleeper. Proceedings of the fiftieth convention of the NLNE, 1946, Atlantic City, New Jersey. PMID- 8479875 TI - Address of President Ruth Sleeper. Proceedings of the fifty-first convention of the NLNE, 1947, Seattle, Washington. One world--one objective for nursing education. PMID- 8479876 TI - Address of President Ruth Sleeper. Proceedings of the fifty-second convention of the NLNE, 1948, Chicago, Illinois. A year of sowing. PMID- 8479877 TI - Address of President Agnes Gelinas. Proceedings of the fifty-third convention of the NLNE, 1949, Cleveland, Ohio. The pressures, problems,and programs of nursing education. PMID- 8479878 TI - Address of President Agnes Gelinas. Proceedings of the fifty-fourth convention of the NLNE, 1950, San Francisco, California. Unified nursing organizations. PMID- 8479879 TI - Address of President Agnes Gelinas. Proceedings of the fifty-fifth convention of the NLNE, 1951, Boston, Massachusetts. Increasing the teacher supply in schools of nursing. PMID- 8479880 TI - Address of President Agnes Gelinas. Proceedings of the fifty-sixth convention of the NLNE, 1952, Atlantic City, New Jersey. Needed: bettereducational programs in nursing. PMID- 8479881 TI - Address of President Lystra E. Gretter. Ninth annual convention of the Superintendents' Society, 1902, Detroit, Michigan. PMID- 8479882 TI - Toward the future, 1953-. PMID- 8479883 TI - Address of President Ida Giles. Tenth annual convention of the Superintendents' Society, 1903, Pittsburgh, Pennsylvania. PMID- 8479884 TI - Address of President Georgia M. Nevins. Eleventh annual convention of the Superintendents' Society, 1905, Washington, D.C. PMID- 8479885 TI - Address of President Annie W. Goodrich. Twelfth annual convention of the Superintendents' Society, 1906, New York, New York. PMID- 8479886 TI - Address of President Maude Banfield. Thirteenth annual convention of the Superintendents' Society, 1907, Philadelphia, Pennsylvania. PMID- 8479887 TI - Address of President Mary Hamer Greenwood. Fourteenth convention of the Superintendents' Society, 1908, Cincinnati, Ohio. PMID- 8479888 TI - Address of President Isabel Hampton Robb. Fifteenth annual convention of the Superintendents' Society, 1909, St. Paul, Minnesota. PMID- 8479889 TI - Address of President Mary Adelaide Nutting. Sixteenth annual convention of the Superintendents' Society, 1910, New York, New York. PMID- 8479890 TI - Address of President Mary M. Riddle. Seventeenth annual convention of the Superintendents' Society, 1911, Boston, Massachusetts. PMID- 8479891 TI - Address of President Mary C. Wheeler. Eighteenth annual convention of the Superintendents' Society, 1912, Chicago, Illinois. PMID- 8479892 TI - Toward international involvement, 1914-1928. PMID- 8479893 TI - [Initial trauma care]. PMID- 8479894 TI - [New AIDS vaccine tested in 8 countries]. PMID- 8479895 TI - [Prostate cancer in Scandinavia. Variations in practice and attitude to radical treatment]. AB - Some controversy persists as to the optimal assessment and treatment of prostate cancer, a lack of consensus reflected in differences in clinical practice. Our survey among departments of urology and general surgery in the Nordic countries showed Danish physicians to be the most conservative, while the most active intervention strategies were found in Finland. PMID- 8479896 TI - [When is Scandinavia getting specialized trauma care? Report from a leading trauma center in the USA]. AB - The specialized care provided at the trauma centre in Baltimore, Maryland, in the USA is described. By means of a sophisticated communications system, prehospital and hospital care are coordinated with a view to providing optimal care to people with various types of injuries. It is suggested how the American experience might be applied to conditions in the Nordic countries in order to improve the quality of trauma care. PMID- 8479897 TI - [Recording of heart arrest according to the Utstein model]. PMID- 8479898 TI - [Health effects in Sweden of the Chernobyl accident]. AB - An international committee (2) which has studied the health and environmental effects of the Chernobyl accident within the borders of the former Soviet Union does not expect that any increase in cancer frequency among adults can be demonstrated epidemiologically. However, the possibility of an observable increase in the incidence of thyroid cancer and increase in juvenile leukemia could not be excluded. The statistics in Sweden is more accurate, though the radiation doses were significantly lower. It would appear to be unlikely that any changes in cancer incidence (even among children), in mental development in children, in malformations or genetic changes ascribable to the Chernobyl accident will ever be demonstrated in Sweden. PMID- 8479899 TI - [Integration of the patient's viewpoint in quality assessment--a new method]. AB - Attempts at evaluating the health services are characterised by the multiplicity of methods used to assess diagnosis, treatment and care--e.g., compliance investigations, consensus and audit methods, and methods that include evaluation by patients. By means of triangulation methods both medical and consumer perspectives can be included in the evaluation. PMID- 8479901 TI - Editing of a tRNA anticodon in marsupial mitochondria changes its codon recognition. AB - RNA editing has been described for organellar genes of protozoa and plants as well as in three cases for nuclear transcripts of mammals. The mitochondrial tRNA for aspartic acid is encoded in the mitochondrial genome of marsupials with the anticodon GCC. However, cDNA from the gene product revealed that the second nucleotide of the anticodon of the tRNA is posttranscriptionally changed to be recognized as an uridine residue. This restores the coding property of the tRNA. Direct sequencing as well as clones of the amplified cDNA indicated that about 50% of the cellular pool of pre-tRNA molecules for aspartic acid is edited. Thus, RNA editing occurs in mammalian mitochondria and can affect the anticodons of tRNAs. PMID- 8479900 TI - Compilation of E. coli mRNA promoter sequences. AB - An updated compilation of 300 E. coli mRNA promoter sequences is presented. For each sequence the most recent relevant paper was checked, to verify the location of the transcriptional start position as identified experimentally. We comment on the reliability of the sequence databanks and analyze the conservation of known promoter features in the current compilation. This database is available by E mail. PMID- 8479902 TI - cDNA cloning and transcriptional properties of a novel GC box-binding protein, BTEB2. AB - We have cloned a cDNA for a novel GC box-binding protein designated BTEB2 from a human placenta cDNA library using rat BTEB cDNA (Imataka et al. (1992). EMBO J. 11,3663-3671. as a hybridization probe. BTEB2 consists of 219 amino acids and contains three contiguous zinc finger motifs at its C-terminus. The zinc finger domains showed 59% and 64% sequence similarity to those of Sp1 and BTEB, respectively. Adjacent to the N-terminal of the zinc finger motifs, a short sequence rich in basic amino acids is conserved between BTEB2 and Sp1. Furthermore, This basic sequence concurs with the N-terminal half of the consensus sequence for basic domains of the proteins containing both helix-loop helix and leucine zipper motifs. The other region of BTEB2 is notably rich in proline, serine, threonine, and alanine residues. BTEB2 expressed in Escherichia coli showed DNA-binding activity whose specificity was closely similar to that of Sp1. Cotransfection experiments using Hepa-1 cells (a mouse hepatoma cell line) with a BTEB2 expression plasmid and GC box-containing reporter plasmids revealed that BTEB2 apparently activated the expression of the CAT activity. Moreover, when BTEB2 was fused to GAL4 DNA-binding domain, the chimeric protein could enhance the transcription through promoters containing GAL4-binding sites. Analysis of the BTEB2 mRNA by RNA blot analysis demonstrated that the mRNA was expressed specifically in testis and placenta with different sizes, 20S and 28S, respectively, among various organs examined. PMID- 8479903 TI - Activity of U-snRNA genes with modified placement of promoter elements in transfected protoplasts and stably transformed tobacco. AB - In higher plants the promoter elements of pol II- and pol III-transcribed U-snRNA genes are identical, comprising a -30 TATA box and an upstream sequence element, USE. The USE and TATA are centred approximately four and three helical DNA turns apart in pol II and pol III genes, respectively, and it is this difference in the element spacing that determines the RNA polymerase specificity of the gene. In this study we have analyzed the effect of spacing mutations on activity of Arabidopsis U2 and U6 genes in transfected protoplasts of Nicotiana plumbaginifolia and in stably transformed tobacco. In the pol III-transcribed U6 gene the insertions and deletions of either odd or even numbers of half helical turns completely inactivate transcription in transfected protoplasts, consistent with the high conservation of the element spacing found in all plant U-snRNA genes. Surprisingly, while insertions of 50 base pairs (bp) or more into the spacer of the pol II-specific U2 gene inactivate transcription, a deletion of 5 bp or insertions of as much as 20 bp decrease transcription by only 40 to 70%. This relaxed requirement for the conserved element spacing is only seen in transfected protoplasts since the same mutant U2 genes are not transcribed in stably transformed tobacco when transcription takes place from the chromosome. The results provide some clues about possible factor interactions at the promoters of plant U-snRNA genes and also offer an example of major differences in transcription between transiently and stably transformed cells. PMID- 8479904 TI - Purification of mouse MEP-1, a nuclear protein which binds to the metal regulatory elements of genes encoding metallothionein. AB - Metal regulatory elements (MREs) shared by metallothionein (MT) gene promoters are essential for metal induction of MT genes. MEP-1, a nuclear protein which binds to these elements has been purified from heavy metal-resistant mouse L cells using footprinting, Southwestern and UV cross-linking techniques to assay its binding activity. The purification scheme, starting from crude nuclear extracts, involved a combination of heparin-Sepharose and MRE-DNA affinity chromatography. The purified protein preparation showed a single polypeptide band of 108 kDa on polyacrylamide gel electrophoresis, and 2D-gel analyses revealed the presence of a protein species migrating as a single population of approximately 110 kDa. MEP-1 does not appear to be glycosylated since it eluted with the flow-through on a Wheat Germ Sepharose column. It was retained by a zinc Chelating Sepharose column suggesting that amino acid residues (i.e., cysteine, histidine) which have an affinity for zinc ions are exposed on the protein surface. Binding studies with the purified protein indicated that it binds specifically to MRE sequences and that the binding can be abolished by a point mutation in the MRE core consensus sequence or by the addition of the chelating agent 1,10-phenanthroline. Binding activity can be restored by the addition of zinc ions to the chelated protein. These results suggest that MEP-1 is one of the major proteins interacting with MRE sequences. PMID- 8479905 TI - The biochemical defects of prp4-1 and prp6-1 yeast splicing mutants reveal that the PRP6 protein is required for the accumulation of the [U4/U6.U5] tri-snRNP. AB - We have raised specific antibodies against the PRP6 protein and shown that the U4, U5 and U6 snRNAs are co-precipitated with this protein. Using splicing extracts prepared from in vivo heat-inactivated cells, we have characterized the prp4-1 and prp6-1 biochemical defects. In inactivated prp4-1 cell extracts, the U6 snRNA content as well as the U6, U4/U6 snRNPs and the [U4/U6.U5] tri-snRNP particles amounts are severely reduced. In inactivated prp6-1 cell extracts, the PRP6 mutant protein is barely detectable. Glycerol gradient analyses indicate that, in these extracts, the [U4/U6.U5] tri-snRNPs are present in very low amounts, but U4/U6 snRNP particles are normally represented. These results establish that the PRP6 protein is required for the accumulation of the [U4/U6.U5] tri-snRNP. We found no evidence for the presence of the PRP6 protein in the U4/U6 particle. PMID- 8479906 TI - A novel method for site specific introduction of single model oxidative DNA lesions into oligodeoxyribonucleotides. AB - Calf thymus terminal deoxynucleotidyl transferase was used to incorporate several products of oxidative base damage onto the 3' end of oligodeoxyribonucleotides. Under the defined conditions described in this report, single residues of dihydrothymine, beta-ureidoisobutyric acid, thymine glycol, urea, 7-hydro-8 oxoadenine, 7-hydro-8-oxoguanine, 5-hydroxycytosine and 5-hydroxyuracil were incorporated into oligodeoxyribonucleotides of different lengths. The reaction is both efficient and cost effective. The 3' termini of the reaction products were suitable substrates for ligation by phage T4 DNA ligase, facilitating greatly the construction of oligodeoxyribonucleotides containing unique and site specific oxidative DNA lesions. PMID- 8479907 TI - Variable effects of the conserved RNA hairpin element upon 3' end processing of histone pre-mRNA in vitro. AB - We have studied the requirements for efficient histone-specific RNA 3' processing in nuclear extract from mammalian tissue culture cells. Processing is strongly impaired by mutations in the pre-mRNA spacer element that reduce the base-pairing potential with U7 RNA. Moreover, by exchanging the hairpin and spacer elements of two differently processed H4 genes, we find that this difference is exclusively due to the spacer element. Finally, processing is inhibited by the addition of competitor RNAs, if these contain a wild-type spacer sequence, but not if their spacer element is mutated. Conversely, the importance of the hairpin for histone RNA 3' processing is highly variable: A hairpin mutant of the H4-12 gene is processed with almost wild-type efficiency in extract from K21 mouse mastocytoma cells but is strongly affected in HeLa cell extract, whereas an identical hairpin mutant of the H4-1 gene is affected in both extracts. The hairpin defect of H4-12 specific RNA in HeLa cells can be overcome by a compensatory mutation that increases the base complementarity to U7 snRNA. Very similar results were also obtained in RNA competition experiments: processing of H4-12-specific RNA can be competed by RNA carrying a wild-type hairpin element in extract from HeLa, but not K21 cells, whereas processing of H4-1-specific RNA can be competed in both extracts. With two additional histone genes we obtained results that were in one case intermediate and in the other similar to those obtained with H4-1. These results suggest that hairpin binding factor(s) can cooperatively support the ability of U7 snRNPs to form an active processing complex, but is(are) not directly involved in the processing mechanism. PMID- 8479908 TI - A chicken RAD51 homologue is expressed at high levels in lymphoid and reproductive organs. AB - Comparisons of the amino acid sequences of three yeast RecA-like proteins, Rad51 and DMC1 from S.cerevisiae and Rad51 from S.pombe, revealed several highly conserved regions. Degenerated oligonucleotides encoding two of these regions were used for the polymerase chain reaction to clone a chicken RecA-like gene. The encoded protein shares 68% and 49% identical amino acids with the Rad51 and DMC1 proteins. The strong sequence conservation between the yeast and chicken genes indicates that RecA homologues are conserved throughout evolution from prokaryotes to higher eukaryotes. High expression of the chicken Rad51 gene was found within the organs of lymphoid and germ cell development suggesting its involvement in lymphoid and meiotic recombination. PMID- 8479909 TI - Different TRE-related elements are distinguished by sets of DNA-binding proteins with overlapping sequence specificity. AB - Several promoter elements with sequence similarity to the prototype TPA responsive element (TRE) were compared by mobility-shift analyses. Activities within whole cell extracts were identified that bind to the TRE-like elements in the collagenase, the somatostatin, and the c-jun promoters. The corresponding factors appeared to differ in their degree of selectivity for these TRE-like sequences. One protein species bound equally well to all TREs. In addition, a subset of specific activities recognised only the somatostatin and the c-jun derived element and one DNA-protein complex had exclusive specificity for the TRE present in the c-jun promoter. By antibody 'supershift' assays some of the protein components of the specific complexes were identified as CREB- and ATF related products. Based on these data we postulate that bZip protein dimers differ in their ability to tolerate variations from the canonical TRE sequence. We propose that TRE-like promoter elements are distinguished by this ability to bind to different subsets of a family of related transcription factors. PMID- 8479910 TI - An insulinoma nuclear factor binding to GGGCCC motifs in human insulin gene. AB - Cell specific expression of the insulin gene is achieved through transcriptional mechanisms operating on 5' flanking DNA elements. In the enhancer of rat I insulin gene, two elements, the Nir and Far boxes, located at positions -104 and 233 respectively and containing the same octameric motif are essential for B cell specific transcription activity. Homologous sequences are present in the human insulin gene. While studying the binding of nuclear proteins from insulinoma cells to the -258/+241 region of the human insulin gene, we observed a previously undetected protein binding site in the intron I region between nucleotides +160 and +175. The binding activity was present in insulin producing cells such as RIN and HIT insulinoma cells but not in fibroblasts or insulin negative fibroblast x RIN hybrid cells. DNAse I footprinting and gel retardation/methylation interference experiments allowed us to define the core binding site of the intron binding factor as a GGGCCC hexamer. This factor is also capable to bind to a related sequence, contiguous to the Far-like element in rat and human insulin genes. The binding of the GGGCCC binding factor in this critical region of the insulin gene enhancer may participate in the regulation of insulin gene expression. PMID- 8479911 TI - Cell-specific expression of helix-loop-helix transcription factors encoded by the E2A gene. AB - The E2A gene encodes transcription factors of the helix-loop-helix family that are implicated in cell-specific gene expression as part of dimeric complexes that interact with E box enhancer elements. It has previously been shown that transcripts of the E2A gene can be detected in a wide range of cell types. We have now examined expression of the mouse E2A gene at the protein level using polyclonal antisera directed against distinct portions of the E2A protein to probe blots of cellular extracts. A 73 kDa protein was identified by this analysis: this protein is highly enriched in cell lines of B lymphoid origin as compared to pancreatic beta-cells and fibroblast cells. The detection of this protein selectively in extracts of lymphoid cells correlates with the presence of the E box-binding activity LEF1/BCF1 in these cells; this binding activity was previously shown to be efficiently recognized by antiserum directed against E2A gene products. Transfection of cells with full length E2A cDNA leads to appearance of protein co-migrating with the 73 kDa protein on SDS gel electrophoresis and co-migrating with LEF1/BCF1 on mobility shift analysis. Our results are consistent with the view that the DNA-binding activity LEF1/BCF1 is a homodimer of E2A proteins; the selective appearance of this putative cell specific transcription factor in B lymphoid cells seems to be attributable, at least in part, to the elevated E2A protein concentrations in these cells. PMID- 8479912 TI - Protection of human endothelial cells from oxidant injury by adenovirus-mediated transfer of the human catalase cDNA. AB - In a variety of disorders, endothelial cells are exposed to high levels of oxidants, generated within the cells and/or consequent to local inflammation. In the context of the sensitivity of endothelial cells to oxidant stress, particularly related to H2O2, we have designed a replication deficient recombinant adenovirus containing the human catalase cDNA (AdCL) to transfer the catalase cDNA to the endothelial cells, in order to augment intracellular anti H2O2 protection. Human umbilical vein endothelial cells that were not infected or infected with control adenovirus maintained low levels of catalase mRNA. Endothelial cells infected with AdCL expressed AdCL-driven exogenous catalase mRNA, as early as 24 hr and at least for 7 days. Catalase protein levels were increased significantly over controls in cells infected with AdCL, as were catalase activity levels, with catalase activity correlated closely with levels of catalase protein. Importantly, when the endothelial cells were exposed to 500 microM H2O2, all the AdCL infected endothelial cells survived, compared to only 37% of the control cells. Thus, a recombinant adenovirus containing the human catalase cDNA is able to infect human endothelial cells in vitro and express high levels of functional intracellular catalase, protecting the cells against H2O2 mediated oxidant stress. These observations support the feasibility of the transfer of catalase cDNA to human endothelium to protect against oxidant injury. PMID- 8479913 TI - Activation and repression of Drosophila alcohol dehydrogenase distal transcription by two steroid hormone receptor superfamily members binding to a common response element. AB - Developmental activation of the Drosophila alcohol dehydrogenase (Adh) distal promoter is controlled by the Adh adult enhancer (AAE). Within this 150 bp, complex enhancer is a small (12 bp) positive cis-acting element that is required for high levels of distal transcription in adult flies and ADH-expressing tissue culture cells. We previously reported that the steroid receptor superfamily member FTZ-F1 binds to this site. We have identified a second steroid receptor superfamily member, DHR39, which also binds to this site. DHR39 is expressed throughout development in transcripts of several sizes. In situ hybridization to embryos has shown that DHR39 RNA is found primarily in the central nervous system, and not in embryonic tissues that express ADH. FTZ-F1 RNA, however, shows temporal-specific patterns similar to those of the distal promoter. FTZ-F1 and DHR39 have identical amino acids in the 'P-box' of the DNA binding domain, suggesting that they have identical DNA recognition characteristics. By electrophoretic mobility shift analysis we show that a DHR39 fusion protein binds specifically to two FTZ-F1 binding sites. By over expressing the full length DHR39 protein in a transient co-transfection assay we have shown that it represses distal Adh expression in a dosage- and binding site-dependent manner. Over expression of an alternative DHR39 open reading frame that lacks part of the putative ligand binding domain does not alter Adh expression. In contrast, over expression of FTZ-F1 specifically activates distal Adh expression. PMID- 8479915 TI - The preprotachykinin A promoter interacts with a sequence specific single stranded DNA binding protein. AB - An element within the Preprotachykinin A (PPT) promoter is highly homologous to an element from the rat type II Na channel promoter. This Na Channel element has been previously proposed to be common to a number of neuronal genes. We demonstrate that the PPT element binds a sequence specific DNA binding protein. The protein binds to only one strand of the PPT element and has little or no specificity for the double stranded DNA species. Gel retardation analysis indicates that the protein is found in both rat neuronal tissue and adult dorsal root ganglia neurons in culture but not in established tissue culture cell lines. Using the PPT element linked to magnetic beads we have been able to demonstrate the enrichment of a protein with a molecular weight of 40k with that of the binding activity. A mechanism for protein binding to the DNA is proposed based on the fact that the region binding the protein is the loop of a larger stem-loop structure in the DNA. PMID- 8479914 TI - Estrogen-inducible and liver-specific expression of the chicken Very Low Density Apolipoprotein II gene locus in transgenic mice. AB - We have examined the chicken Very Low Density Apolipoprotein II (apoVLDL II) gene locus in transgenic mice. A DNA fragment composed of the transcribed region, 16 kb of 5' flanking and 400 bp of 3' flanking sequences contained all the information sufficient for estrogen-inducible, liver-specific expression of the apoVLDL II gene. The far-upstream region contains a Negative Regulating Element coinciding with a DNaseI-hypersensitive site at -11 kb. In transgenic mice, the NRE at -11 kb is used for downregulating the expression to a lower maximum level. The NRE might be used for modulating apoVLDL II gene expression, and may be involved in the rapid shut-down of the expression after hormone removal. PMID- 8479916 TI - Isolation and characterization of cDNA clones encoding the Drosophila homolog of the HMG-box SSRP family that recognizes specific DNA structures. AB - Recently an HMG-box protein denoted SSRP1, for structure-specific recognition protein 1, has been discovered which binds to specific DNA structural elements such as the bent, unwound conformations that occur upon the formation of intrastrand crosslinks by the anticancer drug cisplatin. The SSRP family includes the mouse protein T160, which recognizes recombination signal sequences. In order to delineate functional domains more clearly, a homolog of SSRP1 was cloned from Drosophila melanogaster. This homolog maps to polytene region 60A (1-4) and shares 54% identity with human SSRP1. Comparison of the predicted amino acid sequences among SSRP family members reveals 48% identity, with structural conservation in the carboxy terminus of the HMG box as well as domains of highly charged residues. Interestingly, however, the most highly conserved regions of the protein are in the less well understood amino terminus, strongly suggesting that this portion of the protein is critical for its function. PMID- 8479917 TI - Two cDNAs from the plant Arabidopsis thaliana that partially restore recombination proficiency and DNA-damage resistance to E. coli mutants lacking recombination-intermediate-resolution activities. AB - Escherichia coli ruvC recG mutants lack RuvC endonuclease, which resolves crossed strand joint molecules (Holliday junctions) formed during homologous recombination into recombinant products, and an activity (RecG) thought to partially replace RuvC. They are therefore highly deficient in homologous recombination, and sensitive to UV light and chemical DNA-damaging agents, presumably because of inability to tolerate unrepaired DNA damage by recombinational mechanisms (Lloyd, R.G. (1991) J. Bacteriol. 173:5414-5418). We transformed these mutants with plasmids expressing cDNAs from the plant Arabidopsis thaliana. Selection for bacteria with increased resistance to methylmethanesulfonate yielded two cDNAs, designated DRT111 and DRT112 (DNA damage-repair/toleration). Expression of these plant cDNAs, especially DRT111, restored conjugal recombination proficiencies in ruvC and ruvC recG mutants to nearly wild-type levels. Both plant cDNAs significantly increased resistance of both mutants to UV light and several chemical DNA-damaging agents, but did not fully correct the mutant phenotypes. Drt111 activity, but not Drt112, also increased, to nearly wild-type levels, resistance of recG single mutants to UV plus mitomycin C. The predicted Drt111 and Drt112 polypeptides, 383 and 167 amino acids respectively, show no similarity with one another or with prokaryotic Holliday resolvases. Both appear chloroplast targeted; Drt112 is highly homologous to Arabidopsis plastocyanin. DRT111 and DRT112 probes hybridize only to DNA from closely related plants. PMID- 8479918 TI - Computer-assisted prediction, classification, and delimitation of protein binding sites in nucleic acids. AB - We present a method to determine the location and extent of protein binding regions in nucleic acids by computer-assisted analysis of sequence data. The program ConsIndex establishes a library of consensus descriptions based on sequence sets containing known regulatory elements. These defined consensus descriptions are used by the program ConsInspector to predict binding sites in new sequences. We show the programs to correctly determine the significant regions involved in transcriptional control of seven sequence elements. The internal profile of relative variability of individual nucleotide positions within these regions paralleled experimental profiles of biological significance. Consensus descriptions are determined by employing an anchored alignment scheme, the results of which are then evaluated by a novel method which is superior to cluster algorithms. The alignment procedure is able to include several closely related sequences without biasing the consensus description. Moreover, the algorithm detects additional elements on the basis of a moderate distance correlation and is capable of discriminating between real binding sites and false positive matches. The software is well suited to cope with the frequent phenomenon of optional elements present in a subset of functionally similar sequences, while taking maximal advantage of the existing sequence data base. Since it requires only a minimum of seven sequences for a single element, it is applicable to a wide range of binding sites. PMID- 8479919 TI - Cloning and sequence of the human RecA-like gene cDNA. PMID- 8479920 TI - Nucleotide sequence and secondary structure of the chloroplast group I intron Cr.psbA-2: novel features of this self-splicing ribozyme. PMID- 8479921 TI - Sequence of the dengue virus type 2 (strain PR-159) NS1 gene and comparison with its vaccine derivative. PMID- 8479922 TI - Sox 15, a novel member of the murine Sox family of HMG box transcription factors. PMID- 8479923 TI - Complete small ribosomal subunit RNA sequence of the chiton Acanthopleura japonica (Lischke, 1873) (Mollusca, Polyplacophora). PMID- 8479924 TI - Human ribosomal protein S20 cDNA sequence. PMID- 8479925 TI - Sequence of a cDNA encoding human ribosomal protein L26 and of a cDNA probably encoding human ribosomal protein L6. PMID- 8479926 TI - Cloning and analysis of cDNA for rat histone H1(0). PMID- 8479927 TI - Molecular cloning and DNA sequence of a Dictyostelium cDNA encoding a Ran/TC4 related GTP binding protein belonging to the ras superfamily. PMID- 8479928 TI - DNA sequence of the putA gene from Salmonella typhimurium: a bifunctional membrane-associated dehydrogenase that binds DNA. PMID- 8479929 TI - E. coli host strains significantly affect the quality of small scale plasmid DNA preparations used for sequencing. PMID- 8479930 TI - A simple and rapid amplification procedure for cDNA cloned in dephosphorylated plasmid. PMID- 8479931 TI - Ultrasonic ligation for rapid high-efficiency subcloning in plasmid vectors. PMID- 8479932 TI - Quantitative analysis of anti-CEA antibody accumulation in human colorectal carcinomas. AB - In order to obtain quantitative data on intratumoral antibody accumulation we analyzed resected colorectal adenocarcinomas of 25 patients who had undergone immunoscintigraphy 4-14 days earlier. All had been injected with 0.5-1.0 mg intact anti-CEA antibody (BW 431/26) labelled with 70-80 MBq131I. Correlation of tissue radioactivity concentrations with tumor characteristics revealed significantly higher values in necrotic compared to viable as well as in CEA positive compared to CEA-negative viable tumor tissue indicating action of both specific and unspecific uptake mechanisms. In contrast, diagnostic results of immunoscintigraphy were influenced by tumor size only. 11 of 12 false-negative findings were obtained in tumors < 4 cm in diameter. Since ex-vivo scintigraphy of resected specimens correctly visualized all but one of these lesions, it is concluded that technical limitations of scintigraphy are the main cause of negative results of radioimmunoimaging with 131I-labelled antibodies. PMID- 8479933 TI - [The value of bone scintigraphy in thigh pain following cementless hip prosthesis]. AB - Persisting postoperative pain of the thigh is a common problem of cementless hip endoprostheses occurring in about 15-20% of the patients. We performed a comparative study including patients with (n = 40) and without (n = 45) pain of the thigh. 85 cementless porous-coated anatomic (PCA) hip endoprostheses in 74 patients were examined. All patients underwent clinical examination including a standardized questionnaire, x-ray, and 3-phase bone scintigraphy. Slight or moderate 99mTc-MDP uptake in the area of the greater and lesser trochanter as well as at the tip was a common finding in PCA prostheses in patients without pain and was not a sign of loosening of the hip. Radiologically, there was no difference between patients with and without pain. However, persisting pain of the thigh in patients with PCA prosthesis corresponded with an increased uptake at the tip and the medial and lateral femur, not being a sign of loosening even in this group. The special biomechanical conditions of cementless prostheses causing inhomogeneous intraosseous stress distribution are supposed to be the reason for that. PMID- 8479934 TI - [Prophylactic inhalation of amphotericin B in invasive aspergillosis: a distribution study]. AB - Invasive pulmonary aspergillosis (IPA) during periods of immunosuppression or prolonged neutropenia is a serious condition with high mortality. Prophylaxis is unsatisfactory because of the low effectiveness of systemic administration of amphotericin B (AMB) and because of its side effects. Prophylactic inhalation of AMB by means of a nebulizing system may be able to reduce the incidence of IPA. Therefore, we studied the distribution of nebulized 99mTc-labeled AMB and estimated its particle size. AMB is homogeneously distributed in the lung and partly deposited in the terminal respiratory unit; it remains there with a half life of at least 14 h. Therefore, prophylaxis of IPA with AMB nebulized as described can be recommended. PMID- 8479935 TI - 201Tl reinjection predicts improvement of left ventricular function following revascularization. AB - The aim of this study was to evaluate the correlation between improved Tl uptake in reinjection imaging with improvements in regional wall motion and global ejection fraction following PTCA or aorto-coronary bypass surgery. 19 patients with CHD were investigated and divided into two groups according to their thallium uptake in the reinjection studies. Group I showed additional uptake on reinjection imaging compared to the redistribution image, whereas group II showed no additional uptake. Both groups had a similar number and distribution of affected vessels and location of the leading stenosis. Stress, redistribution and reinjection images were obtained prior to revascularization and evaluated semiquantitatively from a bulls eye scheme. There was a postoperative increase in regional wall motion in group 1 from 5.3 to 8.8% whereas group II did not show a relevant change (6.3 vs 6.0%). The ejection fraction increased II from 55.0 to 66.7% in group I and dit not increase in group II (59.8 vs 58.7%). The overall predictive value of the reinjection image for improvement in wall motion (> 10%) was 91% and for the redistribution image 58%. Increased uptake in reinjection imaging predicts improved ventricular function following revascularization and indeed indicates viable myocardium with reversible functional impairment. PMID- 8479936 TI - [The importance of the radioiodine test for the calculation of the therapeutic dose in benign thyroid diseases]. AB - The aim of this study was to determine the significance of the radioiodine uptake test for predicting the kinetics of therapeutic 131I doses in the treatment of benign thyroid disorders. We studied retrospectively the histories of 518 consecutive patients treated with 131I for hyperthyroidism or autonomous thyroid goiter, with respect to uptake and effective half-life of tracer and therapeutic doses. The mean half-life and uptake of the therapeutic doses were significantly smaller than that of the tracer dose. A comparison of different methods of calculation showed that the radioiodine uptake test is indispensible for dose calculation in radioiodine treatment but a single measurement after 24 or 48 h is sufficiently accurate because, on average, the therapeutic dose was achieved as planned and with the smallest scatter. Average half-lives specific to the disease to be treated may be used in the calculations. PMID- 8479937 TI - [Long term biokinetics of 169Yb following injection as citrate, hydroxyethylethylenediaminetetraacetate and nitrilotriacetate]. AB - 169Yb complexes with known biokinetics in tumour-bearing mice up to 48 h p.i. were injected into healthy mice to study the radionuclide biodistribution in various organs and tissues for 672 h after injection, in order to obtain reliable biokinetic data in an animal model, not affected by tumour-growth, as a basis for the calculation of biological half-life and dose distribution. The results demonstrated the existence of at least two components with different biological half-lives in the organs and tissues investigated. The effective half-lives of these components decreased with increasing stability of the complexes administered. The effective half-life of the fast component was a few hours and that of the slow one between about 200 and 800 h. PMID- 8479938 TI - A new prognosis-oriented classification of chronic glomerulonephritis. PMID- 8479939 TI - [Does a short-term hemodialysis treatment influence function of the pituitary testicular axis in patients with chronic renal failure?]. AB - Abnormal function of the pituitary-gonadal axis is a well documented endocrine abnormality in chronic renal failure (CRF). The purpose of the work was to assess the influence of the short-term haemodialysis treatment on LH, FSH and testosterone secretion. In 17 men dialyzed up to 50 months and 10 non-dialyzed male patients with advanced CRF the test of stimulation with LHRH was done. Results obtained in patients were compared with those assessed in healthy subjects. Significantly higher concentration of LH and FSH and lower concentration of testosterone in serum under basal conditions were found in patients as compared to controls. Basal concentrations of LH, FSH and testosterone in dialyzed patients and in non dialyzed men were similar. The area under the curve of LH, FSH and testosterone in both groups of patients was similar. These results suggest that in men dialyzed shorter than 50 months haemodialysis treatment does not change significantly the function of the pituitary-testicular axis as compared to men with advanced CRF. PMID- 8479940 TI - [Effect of aminophylline on respiratory function in patients with chronic renal failure treated by peritoneal dialysis]. AB - In 8 patients with chronic renal failure aminophylline influence was studied on respiratory function. No changes were seen in lung volumes after 30 minutes of intravenous aminophylline infusion. After 2 weeks of intraperitoneal infusion of aminophylline, maximal ventilation, vital capacity, forced vital capacity and inspiratory residual volume rose significantly. Residual volume and the ratio residual volume/total lung capacity, decreased. This changes may indicate an improved contractility of the respiratory muscles. A rise in the concentration of oxypurines after peritoneal dialysis and a significant improvement in the arterial oxygen tension indicate that aminophylline influences the respiratory function by bronchodilatation and by contractility improvement of the respiratory muscles. PMID- 8479941 TI - [Effect of long term prazosin treatment on secretion of insulin, glucagon, gastrin, and pancreatic polypeptide in patients with essential hypertension]. AB - Secretion of insulin, glucagon, gastrin and pancreatic polypeptide (PP) at basal and test meal stimulation conditions were investigated in 17 patients with essential hypertension (EH) before and after 12 months of treatment with prazosin and in 10 healthy subjects. Before prazosin therapy, patients with EH differ from healthy subject higher insulin and gastrin but lower PP secretion after test meal stimulation. 12 month therapy with prazosin enhanced insulin and suppressed gastrin secretion stimulated by test meal in comparison to the pretreatment values. Prazosin therapy did not influence significantly glucagon and PP secretion. Our results suggest, that long term prazosin treatment markedly influenced insulin and gastrin secretion in patients with EH. PMID- 8479942 TI - [Factors influencing survival in patients with coronary disease. I. Characteristics of examined patients and survival curves]. AB - The group of 683 patients with the significant narrowing (> 70%) of at least one coronary vessel diagnosed by coronarography performed between 1976-1988 in the Institute of Cardiology in Warsaw was followed during one to seven years. The number of patients with a poor left ventricular function was high in the group treated surgically and non surgically. Ejection fraction < 50% was found in 27% and 43% respectively, LVEDP > 12 mmHg (66% and 69%), EDVI > 100 ml/m2 (58% and 70%). Survival curves were calculated in the two different subsets of patients treated surgically and non surgically. Despite some favorite trend toward a better outcome for patients treated surgically the differences were not statistically significant for a whole group. However we showed a significantly higher probability of survival in the subgroup of the three vessel disease treated surgically compared to other treatment. There were no significant differences in survival in patients with one, two, or three vessel disease treated surgically (survival probability of 0.82; 0.78; 0.84 respectively after 7 years). In patients treated non surgically the growing number of diseased vessels worsened the prognosis (survival probability of 0.84; 0.78; 056 respectively). In our observation the differences for better outcome in patients with poor left ventricular function treated surgically did not reach a statistical significance. PMID- 8479943 TI - [Influence of diabetes on the clinical course and hospital mortality of patients with recent myocardial infarction]. AB - In group of 1026 patients with recent myocardial infarction (from program "Streptokinase in acute myocardial infarction"--patients below 70 years old, up to 12 hours from the onset of the symptoms) we analyzed the influence of diabetes on clinical course and hospital mortality. In this group were 77 patients with noninsulin-dependent diabetes (NIDDM), and 21 patients were insulin-dependent diabetes (IDDM). The risk factors of coronary heart disease and myocardial infarction in the past were significantly more often in patients with diabetes than in subjects without diabetes. In hospital mortality was significantly higher (p < 0.05) in group of patients with diabetes (17.3%) than in group without diabetes (9.5%). Reinfarction in the hospital period occurred significantly more often in diabetes group (p < 0.01). Congestive heart failure was observed in 50% patients with diabetes and in 32.3% cases without diabetes (p < 0.01), the left ventricle aneurysm occurred accordingly 9.8% i 5.2% (N.S.). Early ventricular fibrillation and atrio-ventricular blocks occurred with the same frequency in the both groups. We analyzed also the influence of thrombolytic therapy on clinical course in patients with diabetes proving the benefit of this treatment. PMID- 8479944 TI - [Factors influencing survival in patients with coronary heart disease. II. Multivariate logistic function analysis]. AB - A group of 683 patients with the significant narrowing (> 70%) of at least one coronary vessel diagnosed by coronarography performed between 1976-1988 in the Institute of Cardiology in Warsaw was followed during one to seven years. Two hundred ninety of them were treated surgically, 393 non surgically. A multivariate logistic function (MLF) analysis of 10 variables is presented obtained from anamnesis and hemodynamic data and their significance upon survival after 2, 4 and 6 years. In the group treated non surgically the number of narrowed vessels was a factor independently significant after 2, 4 and 6 years. After 4 and 6 years the ejection fraction and the left ventricle end diastolic volume index were also significant. In the group treated surgically none of those were significant after 2 years. After 4 and 6 years anamnesis of arterial hypertonia was significant after 6 years also left ventricle end diastolic volume index. Coefficients calculated from multivariate logistic function analysis allow the calculation of probability of survival for an individual patient. PMID- 8479945 TI - [A difficult diagnostic case of malignant hypertension]. AB - A case of a 62-year old male with malignant hypertension was described. The clinical picture was dominated by the presence of cachexia, polyuria and polyneuropathy. Laboratory examinations revealed highly elevated sedimentation rate, hyponatremia and hypokalemia. Secondary hypertension as well as other diseases with similar clinical symptoms were excluded basing in diagnostic procedures. The authors discuss pathophysiological mechanisms on the base of abnormally elevated activity of the renin-angiotensin-aldosterone system. Unusual body weight loss (approximately 20 kgs), polyneuropathy and irreversible lesion of renal tubules without renal function impairment are emphasized. PMID- 8479946 TI - [Pulsed dose intravenous steroid treatment in the therapy of acute lupus nephritis with renal failure]. AB - The effectiveness of pulse-dose intravenous steroid treatment was studied in acute phase of lupus nephritis with renal failure rapidly progressive despite conventional therapy. On 5-6 consecutive days 1g of prednisolone or methylprednisolone was given intravenously to 33 patients with a mean initial serum creatinine 5.9 +/- 4.1 mg/dl (521.6 +/- 362.4 mumol/l); then the patients were placed on conventional therapy. Immediate remission (group I), lasting at least 6 months, was achieved in 23 patients (69.7%), with a significant decrease of serum creatinine from 4.5 +/- 3.2 mg/dl (397.8 +/- 282.9 mumol/l) to 1.3 +/- 0.7 mg/dl (114.9 +/- 61.9 mumol/l) (p < 0.001) within 3 months. In 19 patients the remission lasted more than a year; till now the longest one is 13 years. In 10 patients (group II), the therapy brought no improvement and they went quickly into terminal renal failure. In this group the initial serum creatinine was 8.9 +/- 3.6 mg/dl (786.8 +/- 318.2 mumol/l), which was much higher than in the I group. All those patients were admitted to chronic dialysis programme; however, 5 of them died during the first 3 months of the treatment. The most frequent complications of the therapy were infections; all but one (a generalized zoster being a cause of death) caused no therapeutic difficulties. Pulse-dose intravenous steroid treatment makes achieving rapid clinical remission possible even in cases of advanced renal failure due to acute phase of lupus nephritis, refractory to conventional therapy. PMID- 8479947 TI - [Mesangium]. PMID- 8479948 TI - Comparison of probiotics maintained by in vivo passage through laying hens and broilers. AB - Cecal colonization by salmonellae may be greatly reduced by inoculating chickens with normal cecal microflora, a phenomenon known as competitive exclusion. Unfortunately, it has not been possible to reliably store active cecal microflora over long time periods, and it is difficult to obtain consistent experimental results with different batches of microflora. In order to overcome these problems, the present authors have maintained active cecal flora through a 2-yr period by in vivo passage through both broiler chicks and layers that were fed a diet containing 5% lactose. Competitive exclusion cultures maintained in laying hens worked as well as cultures from broilers. Cecal microflora from either source excluded both nonlactose-fermenting and lactose-fermenting Salmonella strains. Colonization by both types of Salmonella was reduced even when the competitive exclusion organisms were given as late as 3 days after oral challenge inoculation with Salmonella typhimurium. PMID- 8479949 TI - Effect of dietary lactose on cecal morphology, pH, organic acids, and Salmonella enteritidis organ invasion in Leghorn chicks. AB - The effect of 14 or 19 days of 10% dietary lactose administration on Salmonella enteritidis (SE) colonization and histological, morphometric, and organic acid changes of the ceca were investigated. At Day 13 or 18, chicks were challenged with 10(8) cfu of SE. Chicks were killed and cultured 24 h later. A reduction in the total number of positive SE organ invasions was observed following 14 days (P < .001) or 19 days (P < .005) of treatment in chicks fed with lactose. Histological examination revealed a marked reduction in lamina propria thickness of ceca, as well as subjective epithelial cell proliferation from chicks following either 14 or 19 days of lactose administration. Using morphometric analysis, a reduction in the mean lamina propria thickness in chickens fed with lactose during 14 or 19 days was observed as compared with controls (P < .05). Yet, an increase (P < .05) in the mean epithelial cell length in both lactose treated groups was observed as compared with controls. Lactose decreased luminal pH (P < .05) and increased the concentration of acetic, propionic, butyric, and lactic acid (P < .05). These data indicate that lactose-induced resistance to SE organ invasion is associated not only with an increase in organic acid concentration but also with measurable morphological changes of the cecal mucosa. PMID- 8479950 TI - An evaluation of fructooligosaccharide in diets for broiler chickens and effects on salmonellae contamination of carcasses. AB - Two similar trials were conducted to evaluate the effects of dietary inclusion of fructooligosaccharide (FOS) on live performance and carcass characteristics of broilers and on incidence and level of salmonellae on prechill broiler carcasses. The FOS was fed at two levels (0 and .375%) in a complete factorial arrangement with two levels (0 and 55 mg/kg) of bacitracin methylene disalicylate (BMD) in nutritionally complete diets. Broilers were grown to 49 days of age, and samples were processed to determine dressing percentage, abdominal fat content, and most probable number salmonellae on prechill carcasses. The addition of FOS to nutritionally complete broiler diets at .375% had little consistent effect on growth rate, feed utilization, mortality, carcass dressing percentage, abdominal fat content, or incidence or severity of salmonellae contamination of processed broiler carcasses. There appeared to be an antagonism between FOS and BMD on both live performance and salmonellae contamination of processed broiler carcasses. PMID- 8479951 TI - The effects of shuttle programs upon the growth of broilers and the development of immunity to eimeria species. AB - A floor-pen trial was conducted to investigate the effects of different shuttle programs upon the growth of broilers to 8 wk of age. Nicarbazin, halofuginone, and robenidine, when included in the starter feed for 3 wk, were effective in preventing lesions due to Eimeria. The effects of medication upon performance were apparent, medicated groups gaining more weight by 6 wk and having a lower feed conversion at 6, 7, and 8 wk than the unmedicated controls. There were no significant differences in body weight at 6, 7, or 8 wk or feed conversion at 6 or 7 wk among the medicated groups, whether medication was withdrawn for 7 or 14 days. A decrease in the number of small and medium oocysts in the litter was observed as the trial progressed. Few large oocysts (Eimeria maxima) were seen in the medicated groups. Numbers of oocysts did not increase following withdrawal of medication. Birds from all medicated groups were challenged at 6 wk with oocysts of Eimeria acervulina, Eimeria maxima, or Eimeria tenella. Weight gains were similar to that of the unchallenged controls, indicating that they had acquired immunity to these species of Eimeria. PMID- 8479952 TI - Effect of oligosaccharide additions on nitrogen-corrected true metabolizable energy of soy protein concentrate. AB - In order to determine TMEn response to individual saccharide moieties, five different sugar additions were made to a soy protein concentrate control that contained low levels of oligosaccharides. The sugar additions to the control were made to approximate the amounts of raffinose, stachyose, and sucrose found in soybean meal (SBM). All samples were precision-fed to adult Leghorn roosters to determine TMEn values. The control had a dry matter gross energy (GE) of 4,873 kcal/kg, CP of 73.1%, and TMEn value of 3,757 kcal/kg. Raffinose and stachyose significantly reduced TMEn values for the control. Sucrose did not exhibit this effect. In a second experiment, different levels of stachyose and raffinose were added separately to the control to develop a TMEn dose response curve for these alpha-galactosides of SBM. The TMEn of soy protein concentrate was found to be significantly decreased by stachyose and raffinose inclusion and to be dose dependent. PMID- 8479953 TI - Thyroid hormone and growth hormone regulation of broiler adipocyte lipolysis. AB - Broiler adipocytes in culture were utilized 1) to determine acute and chronic effects of triiodothyronine (T3) and growth hormone (GH) on lipolysis; and 2) to determine whether T3 and GH act synergistically to increase lipolysis. Short-term effects of T3 and GH on lipolysis were determined by measuring glycerol release from adipocytes incubated for 1 h with T3 or GH and glucagon (GLU). To investigate long-term effects, adipocytes were cultured for 24 h with T3, GH, or a combination of T3 and GH before removal of hormones by washing and assessment of lipolysis. Basal and GLU-stimulated lipolysis were not altered by short-term (1 h) incubation of adipocytes with T3 or GH. Pretreatment of adipocytes with T3 for 24 h increased (P < .05) basal lipolysis and lipolysis in the presence of low (.3 to 1.5 ng/mL) doses of GLU. Preincubation of adipocytes with GH for 24 h decreased (P < .05) glycerol release in response to maximal stimulatory doses (3 to 10 ng/mL) of GLU and increased (P < .05) glycerol release in response to .3 ng GLU/mL. Long-term pretreatment of adipocytes with a combination of T3 and GH produced a similar increase in lipolysis with .3 ng GLU/mL as pretreatment with either T3 or GH alone. Thus, T3 and GH did not act synergistically to increase lipolysis from broiler adipocytes. PMID- 8479954 TI - Influence of large doses of ascorbic acid on performance, plasma calcium, bone characteristics, and eggshell quality in broilers and Leghorn hens. AB - Four experiments were conducted using broilers (Experiments 1 and 2) or White Leghorn hens (Experiments 3 and 4) to determine the effects of large doses of dietary ascorbic acid on performance, plasma concentration of total and ionic calcium, bone characteristics, and eggshell quality. A total of 564 male broilers were fed diets containing ascorbic acid (ranging from 0 to 3,000 ppm) from 3 to 7 wk of age. Weight gain and feed conversion were measured, and blood plasma was analyzed for total and ionic calcium. Leg bones (femur, tibia, and metatarsus) were analyzed for bone mineral content, density, and breaking strength. In Experiments 3 and 4, a total of 484 Leghorn hens were fed diets containing ascorbic acid (ranging from 0 to 3,000 ppm) for 4 wk. Egg weight and specific gravity were determined, and plasma and tibiae were analyzed as in Experiments 1 and 2. Results of the broiler experiment (Experiment 2) indicated that plasma ionic calcium was significantly increased (P < .05) in ascorbic-acid-treated birds. Among leg bones examined, femur strength was improved by 16% in birds fed 2,000 ppm of ascorbic acid (Experiment 2). Other bone characteristics were not affected. In the layer experiments (Experiments 3 and 4), egg weight increased up to 5% and egg specific gravity was improved in hens fed 2,000 or 3,000 ppm of ascorbic acid, which also had increased calcium in the blood. Results suggest that large doses of ascorbic acid in the diet influence calcium metabolism, affecting bone and eggshell mineralization in chickens. PMID- 8479955 TI - Effects of sex, heat stress, body weight, and genetic strain on the dietary lysine requirement of broiler chicks. AB - Experiments were carried out to investigate the effects of sex, heat stress (37 C), body weight (heavy and light within strain), and strain of chicks on the dietary lysine requirement of chicks during 8 to 22 days posthatching. A lysine deficient basal diet (.64% total lysine, 23% CP, 3,200 kcal ME(n)/kg) containing corn, feather meal, and soybean meal was supplemented with graded levels of L lysine.HCl to produce growth response curves. The lysine-deficient diet contained .52% true digestible lysine as determined with a precision-fed cecectomized adult cockerel assay (Experiment 1). Hubbard x Hubbard chicks were used in Experiment 2 and New Hampshire x Columbian crossbred chicks were used in Experiments 3 and 4. Experiment 2 compared lysine requirements of male and female chicks. Weight gains between sexes were similar when diets were deficient in lysine, but males grew faster than females when lysine-adequate diets were fed. Male chicks required a higher level of dietary lysine than females for both maximal weight gain and feed efficiency. Also, regardless of sex, the lysine requirement (percentage of diet) for maximal feed efficiency was higher than that for maximal weight gain. In Experiment 3, heat stress reduced weight gain and feed intake of both males and females by about 22%, and it increased the lysine requirement of female but not male chicks. In Experiment 4, light and heavy chicks were selected from male and female populations. Heavy and light chicks exhibited the same dietary lysine requirement for maximal growth. However, the lysine requirement for maximal feed efficiency was higher for heavy birds than for light birds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8479956 TI - Follicle-stimulating hormone-enhanced fibronectin production by chicken granulosa cells is influenced by follicular development. AB - Experiments were conducted in vitro to examine the effect of ovine follicle stimulating hormone (FSH) on various fractions of fibronectin (deposited, secreted in medium, and cell-associated) resulting from culture (12 or 24 h) of chicken granulosa cells isolated from the largest (F1) and third largest (F3) preovulatory follicles as well as from a pool of immature small yellow follicles (SYF). Fibronectin in each fraction was quantified with a specific ELISA. The amount of fibronectin deposited in culture wells containing unstimulated cells increased with time and was greatest in wells containing F1 cells. Follicle stimulating hormone increased the quantity of fibronectin deposited within 12 h by F3 and SYF cells, but not by F1 cells. The magnitude of FSH-enhanced fibronectin deposition was greatest in cells derived from immature SYF. Fibronectin secreted in the medium by unstimulated cells also increased with the stage of follicular maturation. Follicle-stimulating hormone increased the amount of fibronectin secreted in the medium by F3 and SYF cells. The quantity of fibronectin associated with cells was increased by FSH in all cell types. Total (deposited plus medium plus cell-associated) fibronectin production was elevated in a dose- and time-dependent manner when FSH was added to F3 and SYF granulosa cells, but the gonadotropin was without effect in F1 cells. The magnitude of FSH stimulation (fold increase) of total fibronectin production was calculated as a multiple of the unstimulated (control) value for each cell type. The relative change in total fibronectin production resulting from addition of FSH (after 24 h incubation) was .02- to .24-fold in F1 cells as compared with .33- to .92-fold in F3 cells and 2.75- to 4.38-fold in SYF cells. These results indicate that FSH stimulates fibronectin production by chicken granulosa cells, and this stimulatory effect decreases as the follicle matures. PMID- 8479957 TI - Stimulus control of copulatory behavior in male Japanese quail. AB - The copulatory behavior of sexually experienced male Japanese quail was tested using taxidermic models with varying proportions of natural and artificial features. Completely artificial models exerted little control over copulatory behavior, and whole natural body models reliably elicited copulatory behavior. In single model presentation tests, a model containing a natural head and neck with an artificial body was as effective in eliciting copulatory behavior as a whole body model, but a model containing a natural body with an artificial head and neck was largely ineffective. In choice tests, however, males clearly preferred a whole model over a natural head and neck model, and a natural body model over a completely artificial model. These data indicate male Japanese quail do attend to features of body plumage. Furthermore, test procedures can influence conclusions about effective controlling stimuli. PMID- 8479958 TI - Evidence that estrogen binding sites are present in bone cells and mediate medullary bone formation in Japanese quail. AB - Studies were carried out in Japanese quail to characterize the binding of estrogen to bone cells and to determine whether induction of medullary bone by estrogen is mediated by estrogen receptors. First, attempts were made to identify specific, high affinity nuclear binding sites for estrogen with a nuclear exchange assay in oviduct and femora from laying female quail and in liver, kidney, and femora from adult male quail treated with estradiol valerate (2 mg per bird). High-affinity nuclear estrogen binding sites were detected in each of the tissues except femora. Second, estrogen binding sites in femora from male quail were localized by radioautography after treatment with 100 microCi of [3H] 17 beta-estradiol ([3H]-E). Estrogen binding sites were present at 1 and 3 h after administration of [3H]-E, and binding of the radiolabeled hormone was prevented by the simultaneous administration of an excess of radioinert estrogen. Third, estradiol valerate (.4 mg) was given as a bolus to adult male Japanese quail. Five days later, the quail had hypercalcemia due to accumulation of phosvitin in serum, had an extensive network of medullary bone at the femur midshaft, and had reduced cortical bone area. The nonsteroidal, anti-estrogen tamoxifen (2 mg/day) prevented estrogen-induced hypercalcemia, medullary bone formation, and reduction of cortical bone area. Fourth, the estrogen target cells in femora from adult male quail that were induced to differentiate to osteoblasts by estrogen treatment were located by [3H]-proline radioautography as early as 12 h following administration of the hormone. These results are interpreted as evidence that induction of medullary bone is a process mediated by estrogen receptor. PMID- 8479959 TI - Evaluation of cross-contamination on automatic viscera removal equipment. AB - Contamination of poultry carcasses by fecal or ingested material is a major problem in the processing of poultry products. It was determined that the automatic equipment used to process uncontaminated carcasses could be used to clean and reprocess contaminated carcasses and significantly reduce the manual labor required to reprocess these carcasses. The potential for cross contamination of the automatic viscera removal equipment was tested by microbiological evaluation, and it was determined that cross-contamination by this equipment was not a problem. PMID- 8479960 TI - Research note: differential chemotaxis of Physarum polycephalum to Salmonella gallinarum and Salmonella pullorum. AB - The chemotactic and chemotropic responses of the plasmodial stage of the slime mold Physarum polycephalum were used to distinguish Salmonella gallinarum and Salmonella pullorum from 10 Salmonella serovars that are commonly isolated from domestic poultry. Utilizing an in vitro plasmodium agar plate assay method, P. polycephalum was attracted to S. gallinarum and S. pullorum, but the organism was repelled by Salmonella derby, Salmonella dublin, Salmonella enteritidis, Salmonella heidelberg, Salmonella minnesota, Salmonella montevideo, Salmonella newington, Salmonella newport, Salmonella reading, and Salmonella typhimurium. PMID- 8479961 TI - [Medicinal plants of the New World--500 years of discovery in the Americas]. PMID- 8479962 TI - [Biological frost prevention in fish, frogs, flies and pines]. PMID- 8479963 TI - [Potassium agonists: mechanisms of action and therapeutic expectations]. PMID- 8479964 TI - [Preservation today]. PMID- 8479965 TI - A comparative study of facial growth following lip and palate repair performed in sequence and simultaneously: an experimental study in beagles. AB - This study was designed to assess the effects of the commonly accepted sequence of cleft lip and palate repair on subsequent maxillofacial growth and to compare these effects with those resulting from simultaneous lip and palate repair. Using 62 eight-week-old normal beagles, we tested the hypothesis that sequential repair (lip first, palate second) of surgically induced lip and palate defects is less detrimental to maxillofacial growth than simultaneous repair of both surgically created defects. Animals were assigned to one of four groups: two control groups (unoperated and unrepaired) and two experimental groups. Defects simulating cleft of the lip, alveolus, and palate were surgically created in the unrepaired controls and in the experimental animals. In one experimental group, the lip and palate defects were repaired immediately and simultaneously. In the other experimental group--simulating current clinical practice--the lip defect was repaired first at the time that it was created, while closure of the palatal defect was delayed 4 weeks. After the animals were killed at 36 weeks of age, 11 maxillary variables were measured directly from cleaned skulls and analyzed by using univariate and multivariate techniques. Animals that had lip and palate defects closed in sequence had less severe maxillofacial aberrations than animals with simultaneously closed defects. Sequential closure of the defects also had identifiable effects on maxillofacial form. The growth aberrations observed among animals with sequential closure, however, are primarily attributable to surgical creation of the defects and not to the surgical repair. Delaying palate repair is less traumatic to the subsequent growth of the maxillary complex than simultaneous repair of lip and palate defects. PMID- 8479966 TI - Periocular reconstruction: a systematic approach. AB - The records and photographs of 90 patients who underwent reconstructive procedures on the eyelids, canthi, and periocular tissues between 1982 and 1988 were reviewed retrospectively. The defects created by either fresh tissue histologically controlled resection or primary excision were analyzed according to location, size, and degree of resection and visual status. Histologic types included nodular, morphea, and fibrosing basal cell carcinomas; well to poorly differentiated squamous cell carcinoma; and melanoma in situ. The adequacy of both ocular protection and tissue preservation was assessed between 1 and 6 years postoperatively. Anatomic as well as functional reconstructions were performed with a complication rate of 12 percent. There were two tumor recurrences requiring extensive craniofacial extirpation and reconstruction. A systematic method of classifying periocular defects was developed in order to analyze various reconstructive options as well as the type and frequency of complications encountered. This classification system is applicable to primary benign and malignant lesions as well as defects. Analysis of patients who underwent periocular reconstruction in the context of this classification system reveals that larger defects and those involving the medial canthus are more prone to complications. Recurrent complications in the medial and lateral canthal region underscore the necessity of routinely utilizing ancillary procedures such as lacrimal intubation and canthopexy. Recommendations for periocular reconstruction are suggested based on this classification system. PMID- 8479967 TI - The fate of intraoral free muscle flaps: is skin necessary? AB - Intraoral free musculocutaneous flaps can be bulky and inflexible for reconstruction of mucosal and soft-tissue defects to the head and neck. Free muscle flaps alone can be much less bulky and restore better contour than musculocutaneous flaps. When using free muscle flaps, however, it was felt that a skin graft was needed for proper epithelialization without significant contracture. Nine patients, average age 59 years (range 42 to 71 years), six males and three females, underwent extirpation of head and neck tumors and reconstruction with free muscle flaps only. Mucosal defects from 4 x 4 to 12 x 10 cm (four floor of mouth, five hard palate) were filled. Reconstruction was done with seven free rectus abdominis muscle flaps and two internal oblique/iliac bone flaps. All flaps survived with no significant complications. There was one minor abdominal wound separation. All patients who were able to swallow started oral feedings by 2 weeks postoperatively. Total epithelialization of even the large defects was completed by 8 weeks. Histologic assessment revealed an early fibrin layer over the muscle at 1 week with eventual epithelialization that was indistinguishable microscopically from normal surrounding mucosa. There was some contracture in all the flaps, but this was not clinically significant, even in the large defects. Intraoral free muscle flaps offer a safe and reliable reconstructive method that has led to a good functional result. PMID- 8479968 TI - Familial medial telangiectatic nevus: variant of nevus flammeus--port-wine stain. AB - Six families in which a few members, in three generations, were affected with medial telangiectatic nevus (salmon patch, stork bite, angel's kiss) on the forehead, glabella, upper eyelids, upper lip, nose, and nuchal and occipital areas are presented. This is a mild variant of lateral telangiectatic nevus (nevus flammeus, port-wine stain) that disappears in about 50 percent of patients during the first years of life. In one family, lateral telangiectatic nevus (nevus flammeus, port-wine stain) and superficial (strawberry) hemangioma coexisted with medial telangiectatic nevus. This paper discusses the familial incidence of medial telangiectatic nevus and a new modality of treatment. Moreover, the paper presents a classification of vascular malformations and proposes a new terminology. PMID- 8479969 TI - Botulinum A toxin for treatment of aberrant facial nerve regeneration. AB - Twelve patients with involuntary synkinetic eyelid closure were given 40 injections of botulinum A toxin. Temporary improvement in involuntary eyelid closure was observed in all 12 patients. Eleven of the 12 patients desired repeated injections. Dose requirements for this indication were compared with doses used in 697 injections in 112 patients with essential blepharospasm and Meige syndrome. Additionally, dose comparisons were made with 269 injections in 71 patients with hemifacial spasm. Dose requirements needed to treat aberrant regeneration of the facial nerve were substantially less than needed to treat blepharospasm and Meige syndrome. The dose requirement was similar to that in hemifacial spasm treatment. The reason for the differences probably relates to existing muscular denervation associated with hemifacial spasm and aberrant facial nerve regeneration. PMID- 8479970 TI - Reduction mammaplasty and correction of ptosis: a personal technique. AB - New upper pedicle reduction mammaplasty and mastopexy techniques are presented. The surgical steps are described point by point. An analysis is made of the results obtained in 25 patients who underwent surgery between November of 1987 and November of 1988 and were examined in December of 1990 with a mean follow-up of 31.5 months. An assessment was made of the postoperative ptosis, which was minimal in 76 percent of patients. The overall assessment of breasts was satisfactory (good mammary morphology and a correct position of the nipple-areola complex). Nipple-areola complex sensitivity was unchanged in 80 percent of patients. Good-quality inframammary scars were observed in 92 percent of patients, with scar length never exceeding 4 cm. The overall complication rate was 32 percent, but only 12 percent were major complications. The technique presented is excellent when the quantity of glandular tissue to be removed is less than 400 gm, and it is not therefore recommended for gigantomasties. PMID- 8479971 TI - An in vivo study of the effect of various breast implant filler materials on mammography. AB - Silicone breast implants have the potential to interfere with mammography through a variety of different mechanisms. One important factor is the radiopacity of the implant. A comparison was made of the effect of six different implant filler materials on visualization of known breast lesions in a living subject. The materials studied were normal saline, a triglyceride solution, silicone gel, a solution of 50% polyvinylpyrrolidone (PVP) in saline, a solution of 10% PVP in saline, and a solution of 2.5% PVP in glycerine. The ease with which known breast lesions could be identified through different materials varied dramatically. The poorest visualization was through the silicone gel-filled implant. The best visualization was through the prosthesis containing a triglyceride solution. Physical density, atomic number, and electron density are the factors which determine the radiopacity of materials used to fabricate breast implants. Radiopacity, in turn, affects the ease with which breast lesions can be imaged in vivo. The radiologic characteristics of filler materials will be an important consideration in the design of future breast implants. PMID- 8479972 TI - The relative radiolucencies of breast implant filler materials. AB - Breast implants in current use utilize silicone gel for filler material. One substantial drawback of silicone gel is its radiodensity, resulting in the obscuration of breast tissue on mammography. The relative radiolucencies of silicone gel, saline, breast tissue equivalent, triglycerides (peanut oil), and polyvinylpyrrolidone (Bio-Oncotic gel) were determined by using standard mammographic equipment. Visibility through these materials was compared by using a standard breast phantom as background. The x-ray dosage necessary to create each mammographic image was measured. Peanut oil provided the clearest image of the phantom artifacts, required the least radiation exposure, and was approximately four times more radiolucent than the saline or Bio-Oncotic gel and about 45 times more radiolucent than silicone gel. As improved implant filler materials are being sought, triglycerides maintain superior radiographic properties. PMID- 8479973 TI - Capsular tissue: a new local flap. AB - Capsular tissue, the interface that forms between an implanted device and the body's own soft tissues, has recently been shown to develop its own unique blood supply. This capsular tissue with its extensive vascular plexus has not been described previously as an isolated flap. The purpose of our study was to determine whether an isolated flap of capsular tissue would survive as a local pedicle flap and provide enough inherent vascularity to support a skin graft. Isolated expanded and nonexpanded capsular flaps were compared by using 20 expanders (10 expanded and 10 nonexpanded) in two mixed-breed female pigs. Expanded and nonexpanded capsular flaps were elevated 8 weeks following expander placement. These flaps were raised on their capsular bases alone, and skin grafts were placed onto the capsular surfaces. All the expanded capsular flaps and their skin grafts had 100 percent survival. Skin grafts on the nonexpanded flaps survived an average of 28 percent, with graft survival corresponding to flap survival. This study confirms that flaps of isolated expanded capsular tissue survive and provide enough inherent vascularity to support a split-thickness skin graft. PMID- 8479975 TI - Endogenous versus toxin-induced diabetes in rats: a mechanical comparison of two skin wound-healing models. AB - This study was designed to compare skin wound healing in three groups of Wistar rats: normal, genetically diabetic, and streptozotocin-induced diabetic. All diabetic animals received daily insulin. Full-thickness midline dorsal skin wounds were analyzed biomechanically for strength, toughness, and elasticity (Young's modulus) at 1 and 3 weeks after wounding. Wounds from normal controls were the strongest, toughest, and least compliant. Genetically diabetic rat wounds were the weakest and had the lowest elastic modulus. Wounds from the streptozotocin-induced rats were intermediate for all parameters measured (ANOVA, p = 0.001). Toxin-induced diabetes is less detrimental to skin wound healing than diabetes of endogenous origin. Whether this is due to basic differences in the models or to differences in duration of diabetes is unknown. PMID- 8479974 TI - Ventral/incisional abdominal herniorrhaphy by fascial partition/release. AB - Ventral/incisional abdominal hernias following celiotomies continue to be a vexing problem for both patients and general and plastic and reconstructive surgeons, since no universally applicable preventive or reconstructive techniques have evolved. With reference to reconstruction, for example, primary repair is associated with a high incidence of recurrence; utilization of synthetic mesh is susceptible to extrusion, infection, and intestinal fistulization; and employment of truncal or extremity, free or rotational, myofascial flaps is associated with the morbidity of the procedure per se. By contrast, the use of fascial partition/release of the components of the abdominal wall employing bilateral parasagittal relaxing incisions in the obliquus externus abdominis and/or transversus abdominis fascia facilitates coaptation of the linea alba and obviates the aforementioned morbidity. This technique was utilized electively in seven adult patients with large defects of the anterior abdominal wall. In addition, for two patients, synthetic nonabsorbable mesh was applied superficial to the midline fascial closure. During a mean follow-up interval of 18 months (range 6 to 36 months), each patient healed per primum without evidence of eventration or herniation. The theoretic and pragmatic advantages of this technique are discussed. The use of fascial partition/release for reconstruction of abdominal wall defects should be part of the armamentarium of all herniotomists. PMID- 8479976 TI - Microbiology and healing of the occluded skin-graft donor site. AB - Delayed healing of skin-graft donor sites may be costly and life-threatening, especially in patients with large body surface area burns. A donor site dressing should maximize the ability of the wound to heal without increasing the risk of local infection, systemic infection, or both. Specifically, the possibility of a secondary infection may either slow the healing process or ultimately convert the donor site into a full-thickness skin loss. A number of materials ranging from gauze to biologicals have been investigated for use as donor site dressings. The use of hydrocolloids for donor sites has been widely studied and has shown improved healing rates over the rates reported for conventional dressings. Our recent study using hydrocolloids confirmed earlier research that showed fewer infections and more rapid donor site healing. PMID- 8479977 TI - Prefabricated flaps using tissue expanders: an experimental study in rats. AB - The aim of this study was to determine if muscle vascularized pedicle flaps (MVP flaps) elevated in expanded tissue on the rat would survive to the same or greater area than flaps elevated in nonexpanded tissue. The animals were divided into three groups: group I (n = 10), with a tissue expander; group II (n = 10), with a tissue expander but not expanded; and group III (n = 10), with a thin silicone sheet (Biobrane). The mean surviving area of group I (96.6 +/- 3.6 percent) was statistically higher than that of group II (73.2 +/- 24.7 percent) (p < 0.05) and group III (59.5 +/- 25.1 percent) (p < 0.005). These experiments demonstrate that there is a larger area of flap survival in expanded muscle vascularized pedicle flaps than that found in nonexpanded flaps in rats. The mechanism of increased vascularity associated with tissue expansion is still unclear, but microangiography of flaps showed increased vascularity of the pedicle itself, especially in group I. PMID- 8479978 TI - Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen. AB - The morphologic events in the microcirculation that lead to reperfusion injury of ischemic skeletal muscle remain incompletely understood. The purpose of this experiment was to evaluate leukocyte endothelial adherence characteristics and dynamic changes in microvessel caliber during reperfusion of an in vivo skeletal muscle ischemia preparation. In addition, the effect of hyperbaric oxygen treatment on these microcirculatory changes also was studied. An intravital microscopy preparation of a transilluminated gracilis muscle in 27 rats was used to observe a total of 101 arterioles and 63 venules (13 to 73 microns diameter). Baseline hemodynamics were videotaped for 30 minutes following muscle isolation. The animals were divided into six groups: (1) sham, no ischemia, (2) 4 hours of global ischemia only, (3) no ischemia plus hyperbaric oxygen (one 2.5 ATA/1 hour of treatment with 100% oxygen), (4) 4 hours of ischemia plus hyperbaric oxygen during ischemia, (5) 4 hours of ischemia plus hyperbaric oxygen immediately on reperfusion, and (6) 4 hours of ischemia plus hyperbaric oxygen 1 hour after reperfusion. Changes in arteriolar and venular diameters at specific times during 3 hours of reperfusion were recorded, and the number of adherent and slow-rolling leukocytes in 100-microns venular segments were counted and compared with baseline measurements. The proximity of arterioles to venules was classified as adjacent (< 15 microns) or distant (> 15 microns). No significant changes in leukocyte endothelial adherence or arteriolar diameter were noted in group 1 sham or group 3 nonischemic hyperbaric oxygen-treated rats when compared with baseline measurements. A significant increase in adherent leukocytes was observed in group 2 ischemic venules (+14.9 +/- 2.5) within 5 minutes of reperfusion, which was maintained for 3 hours. Reperfusion measurements of arteriolar diameter in group 2 ischemic muscle preparations demonstrated an initial vasodilation that was followed at 1 hour by a progressive and severe vasoconstriction (-46.9 +/- 11.3 percent at 3 hours) in arterioles adjacent to venules that was not seen in distant arterioles. The increase in adherent leukocytes seen in group 2 ischemic venules was significantly reduced by hyperbaric oxygen treatment given during ischemia (group 4) or up to 1 hour during reperfusion (groups 5 and 6). In addition, the progressive ischemic arteriolar vasoconstriction was inhibited in all groups (4, 5, and 6) treated with hyperbaric oxygen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8479980 TI - Comparison of the contact neodymium:YAG and carbon dioxide lasers for skin deepithelialization. AB - The application of laserbrasion by the carbon dioxide (CO2) laser for skin deepithelialization previously has been proven efficacious in numerous clinical experiences. This study in adult Sprague-Dawley rats was designed to compare those known effects of the CO2 laser with the contact neodymium:yttrium-aluminum garnet (Nd:YAG) laser for skin deepithelialization, since tactile feedback from the handpiece of the latter is a theoretical advantage. This proved that although the contact Nd:YAG laser does have the capability to achieve skin deepithelialization, when compared with more conventional methods, it is laboriously inefficient and therefore at present impractical. PMID- 8479979 TI - Laser-assisted microvascular anastomosis of human adult and placental arteries with expanded polytetrafluoroethylene microconduit. AB - Laser-assisted microvascular anastomoses can be performed more quickly than sutured anastomoses, yet manifest similar patency rates and tensile strength. This study was undertaken to determine if in vitro laser-assisted microvascular anastomoses could be created between human adult arteries (anterior tibial arteries), human placental arteries, and expanded polytetrafluoroethylene microconduits. A CO2 laser was applied in single or continuous bursts with a matrix of variables encompassing power P = 80 to 160 mW, spot size SS = 150 to 500 microns, and exposure time EXP = 1.0-second continuous exposure (n = 2 each composite setting). The endpoints measured to assess the ability to laser-weld vessels were morphologic appearance by scanning electron microscopy and bursting strength. Scanning electron microscopy revealed apparent fusion of human placental arteries and human adult arteries to expanded polytetrafluoroethylene microconduits at settings of P = 130 mW, SS = 300 microns, and EXP = 1.0 second, though bursting pressure at all settings was less than 10 mmHg. Laser-assisted microvascular anastomoses of human placental artery to human placental artery and human adult artery to human adult artery were successful at this setting, though bursting pressures of anastomoses incorporating placental vessels were significantly weaker than those created with adult tissue. The relative weakness of laser-assisted microvascular anastomoses incorporating placental arteries might be explained by qualitative or quantitative differences in vessel wall collagen, as seen in fetal tissue, and deserves further characterization. PMID- 8479981 TI - Extended wrap-around flap for reconstruction of the finger with recurrent arteriovenous malformation. AB - Treatment of arteriovenous malformations of the finger is difficult because complete resection of malformations by ligation or en bloc resecting methods is impossible. We used an extended wrap-around flap consisting of a combined wrap around flap and a dorsalis pedis flap to reconstruct the soft-tissue defects following complete resection of a recurrent malformation in the index finger. This method has two advantages: no postoperative recurrence of the malformation is expected, and the affected finger can be preserved. However, it is indicated only for malformations with no invasion to the bone and localized in one finger. PMID- 8479982 TI - The form-ative years. PMID- 8479984 TI - Double fillet of foot free flaps for emergency leg and hand coverage with ultimate great toe to thumb transfer. AB - A 42-year-old woman presented with avulsion amputation of her right leg 14 cm below the knee joint and a hemihand amputation of the opposite hand. Two free flaps, taken from the amputated foot, were used to cover the injured extremities. The sole fillet flap was used to preserve length and cover the injured leg, while the dorsal fillet flap covered the injured hand and provided ectopic storage for the great toe. The great toe was later transferred on a pedicle for thumb reconstruction. Spare parts surgery is now a well-accepted technique. This case demonstrates maximum utilization of amputated parts for functional and aesthetic reconstruction. PMID- 8479983 TI - Salvage replantation of two fingers from a nonreplantable midpalm. AB - To achieve better functional results following mutilating multidigital trauma, every effort should be made to maximize the ultimate function of the hand, and the plan of replantation should be guided accordingly. All usable parts should be salvaged from the amputated nonreplantable areas. A patient is reported in whom two fingers taken from the nonreplantable midpalm were used to reconstruct the thumb and ring fingers, ultimately improving the overall quality of the patient's life. PMID- 8479985 TI - Magnetic resonance imaging of the nose with surface coils: a new technique to evaluate functional and aesthetic problems. AB - Determining the preoperative functional and aesthetic anatomy has been of critical importance to surgeons planning nasal procedures. Beyond skilled clinical examination, few objective studies exist to aid the surgeon. Magnetic resonance imaging (MRI) represents a potentially excellent method for precise anatomic imaging of the nose. Unlike computed tomography (CT) and conventional x rays, MRI involves no radiation. Similar to CT, however, MRI can provide computer enhanced three-dimensional and quantitative airway data. Full-head MRI has proven sensitivity in evaluation of tumors of the brain and sinuses and is the imaging modality of choice for many soft-tissue tumors. Due to the relatively high cost of conventional full-head MRI scanning ($600 to $1200 per scan), MRI of the nose utilizing full head scanning technique has been limited. The recent development of small field of view surface coils has enabled higher-resolution nasal scans at a fraction of the scanner time and cost ($200 to $500) of conventional MRI scans. We have developed a protocol utilizing a small field of view coil which results in reproducible high-resolution nasal scans requiring less than 6 minutes of scanner time. This protocol has been used in both the diagnosis and follow-up of patients with traumatic and congenital nasal and septal deformities. Image resolution obtained using the protocol is significantly better than with conventional coils. This technique is excellent for both diagnosing and documenting nasal anatomy and pathology. PMID- 8479986 TI - Central tongue reduction for macroglossia. AB - Unhappy with our postoperative results from standard tongue reduction methods, we have developed a central tongue reduction technique. This technique allows for alteration of the tongue base as well as tongue height and width while minimizing postoperative scarring. Although the technique and its associated surgical complications are in some ways comparable with the standard tongue reduction methods, our postoperative polysomnographic and tongue functioning results are improved. It is noteworthy that none of our patients had worse speech postoperatively and that our one Down syndrome patient had improved speech. Our indication for central tongue reduction is macroglossia of any sort in appropriate patients. PMID- 8479987 TI - A lip guard to protect repaired unilateral cleft lip in adults. PMID- 8479988 TI - Circumferential wiring for fractures (Le Fort types) of the maxilla. PMID- 8479989 TI - Facial artery musculomucosal flap. PMID- 8479990 TI - Ideal approach to management of chronic nonhealing ulcer of the foot: basic principle of surgery revisited. PMID- 8479991 TI - Enterocutaneous fistulas treated successfully by a turnover flap from surrounding tissue reinforced by musculocutaneous flaps and other local flaps. PMID- 8479992 TI - The art of plastic surgery. PMID- 8479993 TI - Periareolar mammaplasty technique with silicone supporting sheeting. PMID- 8479995 TI - Computed tomography for diagnosis of deep venous thrombosis in burn patients. PMID- 8479994 TI - Proper terminology for status of breast implants. PMID- 8479997 TI - Local flap template versus the fan principle for skin flaps. PMID- 8479996 TI - Acute management of the burned patient. PMID- 8479998 TI - The monobloc frontofacial advancement: do the pluses outweigh the minuses? AB - The results of 32 patients who underwent transcranial monobloc frontofacial advancement by the senior author (Wolfe) are examined. Fifteen of the patients were Crouzon's and 17 were Apert's, 14 of whom also underwent simultaneous facial bipartition. The ages ranged from 7 months to 14 years. Although a transcranial facial advancement carries with it substantial risks, with careful consideration of airway control, the anterior cranial base dura, and the retrofrontal dead space, the procedure is recommended for carefully selected patients. The indications and contraindications for the procedure in various age groups are given. PMID- 8479999 TI - Complications with facial advancement: a comparison between the Le Fort III and monobloc advancements. AB - Certain procedures for facial advancement may carry greater risk than others. While many believe that separating the cranial base by monobloc advancement leads to a higher complication rate, no comparative series between the Le Fort III and monobloc advancements has ever been reported. We reviewed our series of these different techniques. Over a 15-year period, 29 patients underwent 30 surgical procedures, with either a midfacial or frontofacial advancement. The average age of patients at the time of surgery was 12 years, with a range from 3 to 26 years. There were 20 Le Fort III and 10 monobloc advancements. Follow-up averaged 4 years, with a range from 10 weeks to 13 years. There were no deaths in this series. The infectious complications differed significantly between the two groups, with all major infections occurring in the monobloc group. The noninfectious complications (2 major and 20 minor) were proportionately distributed between the Le Fort III and monobloc groups. Aesthetic results of the midface, judged by the percentage of revisions necessary, were found to be the same between the two procedures. Aesthetic results were noted to correlate strongly with age at the time of surgery, with the older patients being judged as having a better aesthetic result and most of the younger patients requiring a repeat of the facial advancement. We conclude that while we were unable to determine any definitive aesthetic advantage of one procedure over the other in our series, there was a significantly higher infection rate with the monobloc advancement. On the basis of these results, we recommend a staging of the forehead and midfacial advancements. PMID- 8480000 TI - Median facial dysplasia in unilateral and bilateral cleft lip and palate: a subgroup of median cerebrofacial malformations. AB - The median facial dysplasia group of patients is a unique, distinct, definable group characterized by mid-line facial deficiencies in the presence of a unilateral or bilateral cleft lip with or without cleft palate and without clinically detectable anomalies of the brain. This group of patients comprised 2 percent of new cleft lip and palate patients. The midline facial deficiencies in median facial dysplasia are characterized by a poorly defined Cupid's bow, absence of the labial frenulum and anterior nasal spine, deficient columella, and poorly developed septal cartilage and premaxilla. One of the central incisors may be absent or rudimentary. There are no definable gross abnormalities of the brain. The results of intelligence tests of median facial dysplasia patients have a normal distribution and are not significantly different from those of a noncleft normal population. Unoperated and operated median facial dysplasia patients all have typical midfacial growth disturbances below the norm for their ages. The classification of median facial dysplasia patients as well as other median cerebrofacial anomalies, the embryologic basis of these deformities, and the clinical results of their treatment are helpful in understanding some of the problems related to the treatment of the cleft lip and palate patient. Median facial dysplasia patients demonstrate an inherent potential for poor midfacial growth. Deficiencies of soft tissue such as a lack of the Cupid's bow make it difficult to reconstruct the lip and nose satisfactorily. PMID- 8480001 TI - Rigid and non-rigid kinetic depth effect with rotating discrete helices. AB - To examine the conditions in which human observers fail to recover the rigid structure of a three-dimensional object in motion we used simulations of discrete helices with various pitches undergoing either pure rotation in depth (rigid stimuli) or rotation plus stretching (non-rigid stimuli). Subjects had either to rate stimuli on a rigidity scale (Experiments 1 and 2) or to judge the amount of rotation of the helices (Experiments 3 and 4). We found that perceived rigidity depended on the pitch of the helix rather than on objective non-rigidity. Furthermore, we found that helices with a large pitch/radius ratio were perceived as highly non-rigid and that their rotation was underestimated. Experiment 5 showed that the detection of a pair of dots rigidly related (located on the helix) against a background of randomly moving dots is easier at small phases in which the change of orientation across frames is also small. We suggest that this is because at small phases the grouping of dots in virtual lines does occur and that this may be an important factor in the perceived nonrigidity of the helices. PMID- 8480002 TI - Context-produced increase in visibility. AB - It has not been clearly shown that context (e.g., three lines of a square) increases the visibility of a feature (e.g., the fourth line of the same square). To investigate this possibility, four sets of context+feature, context, feature, and BLANK (empty field) stimuli were used. For three out of the four sets, the context+feature stimulus was less likely to be falsely identified as the context and BLANK stimuli (i.e., the stimuli without the feature) than was the feature stimulus. For the same three sets, discriminating between the context+feature and context stimuli produced fewer false identifications (FIs) than discriminating between the feature and BLANK stimuli. THE CONCLUSION: the context components of context+feature stimuli increased the visibility of the feature components of the same stimuli. PMID- 8480003 TI - Aging and temporal discrimination of brief auditory intervals. AB - In a duration-discrimination experiment, young adults (mean age = 25.1), middle aged adults (mean age = 45.5), and older adults (mean age = 64.6) were presented with two very brief auditorily marked intervals per trial, and their task was to decide which of the two was longer in duration. An adaptive psychophysical procedure was used to determine difference thresholds in relation to a constant standard interval of 50 ms. It was found that duration-discrimination performance was unaffected by age; all three age groups yielded a difference threshold of approximately 17 ms. It was concluded that the ability to discriminate durations of very brief auditory intervals appears to be based on an underlying timing mechanism that does not slow down with advancing adult age. PMID- 8480004 TI - A psychophysiological analysis of response-channel activation and outcome states in Eriksen's noise-compatibility task. AB - Eleven subjects were tested with a modified version of Eriksen's noise compatibility task. Four noise conditions were realized--neutral, compatible, fully incompatible, and partially incompatible context. Target and flanking stimuli had an intrinsic association to either the left- or the right-hand side. As a response subjects pulled, with either their left or their right hand, an ordinary bicycle handbrake from a preload position towards a stop. The EMG from the forearm muscles and the movement trajectory were recorded continuously. Trials were categorized according to the outcome states, i.e., whether a full movement or only a rudimentary EMG activation had occurred in the correct and in the incorrect response channels, respectively, and whether the correct-channel activation was leading or lagging. Incompatible noise delayed information transfer and increased the likelihood of errors, while compatible noise had an opposite effect, i.e., it facilitated transfer and reduced the likelihood of errors. The effect of noise on transfer times was the same for all outcome states. Moreover, in all cases, noise had an effect on transfer times only up to the point of EMG onset, while it left movement-execution times unaffected. These findings are seen as contradictory to a strong continuous flow conception according to which any response-related change in the input channel is continuously and immediately transferred to the response-execution device. At least the final stage of movement control seems to be autonomous and not subject to input control, except for the case that a movement already initiated has to be aborted completely. PMID- 8480005 TI - The effects of sleep deprivation and incentives on human performance. AB - This study explores whether KR (knowledge of results) and reward compensate for the negative joint effects of sleep deprivation and signal degradation in a choice-reaction task. The negative effect of signal degradation on performance was aggravated by sleep loss and time-on-task, whereas KR improved performance, especially when signals were degraded. Reward changed the effects of time-on-task owing to lack of sleep. Performance was also improved by a brief task interruption after 30 minutes' work, with 5 more minutes to go. These results can be interpreted in terms of the performance model of Sanders (1983), which links energetic mechanisms to stages of information processing. A lack of energetic supply from the arousal mechanism to perceptual processing, induced by signal degradation, sleep deprivation, and time-on-task, was effectively counteracted by KR:KR enables the mobilization of effort to compensate for this lack of arousal. The relation between reward and KR is not yet clear. The interruption effect suggests that the influence of time-on-task is not due to loss of arousal, but causes a reallocation of resources by effort. PMID- 8480006 TI - Is the brain an effective Turing machine or a finite-state machine? AB - A theorem presented by Hornik, Stinchcombe, and White (1989) suggested the possibility that connectionist networks could be effectively Turing machines. Levelt (1990) argued that the theorem of Hornik et al. only implies that networks are finite-state machines and are therefore not capable of generating the very unlimited productivity of symbol systems. Yet it can be argued that all real machines, including the brain, are finite-state machines. If so, no real machine actually possesses the very unlimited productivity of symbol systems. So any model of actual behaviour should capture the limitations on productivity inherent in the situation. Thus connectionist networks can be valuable models in psychology, precisely because they are finite-state machines. PMID- 8480007 TI - Children with disabilities and the Children Act: who will assess their needs? AB - The Children Act focuses attention on meeting the assessed needs of children with disabilities. General practitioners (GPs) and Community Child Health (CCH) doctors in one health district were asked by postal questionnaire who it was who currently assessed such needs and who would do so in the future. The involvement of GPs (15) varied from none (1) to regular reassessment (3). Nearly all (14) treated acute illnesses but educational assessments were assigned to CCH doctors. Community doctors (9) had a clearer idea of their role including regular reassessment (9), education assessment (9) and interagency liaison (3). Both groups complained of poor communication with each other and with hospital services. To fulfil the requirements of the Children Act, community child health services, family health services authorities and district health authorities will have to specify how and by whom children with disabilities are identified and assessed. Arrangements will vary according to local service development. These arrangements, and the resulting liaison with other agencies, should be specified in National Health Service contracts, thus improving communication and cooperation. PMID- 8480008 TI - A survey of community child health audit. AB - Community child health medical audit is established in most districts surveyed. A minority have integrated audit with hospital paediatric units. Very few districts use an external auditor. Subject audit is preferred to individual performance audit and school health services were the most common services subjected to medical audit. The need for integrated audit and audit forms suitable for use in the community services is discussed. PMID- 8480010 TI - Investigation of smoking habits among 14-17-year-old boarding school pupils: factors which influence smoking status. AB - A questionnaire-based investigation was performed to elucidate factors with possible influence on smoking status in 557 14-17-year-old boarding school pupils. A representative sample of boarding school pupils in Denmark participated. Before entering boarding school an increased risk of being a smoker was present if a majority of one's schoolmates were smokers (odds ratio 5.9; P < 0.0001); if parents were not living together (odds ratio 2.1; P < 0.005); if older brother or sister was a smoker (odds ratio 3.1; P < 0.0001); and if both parents smoked (odds ratio 1.9; P < 0.01). After changing to boarding school there was an increased risk of starting to smoke if a majority of the schoolmates were smokers (odds ratio 4.6; P < 0.0001). Believing that smoking causes damage to the smokers' own health decreased the risk (odds ratio 2.9; P < 0.01). More efficient smoking prevention programmes should be created by aiming particularly at the special problems encountered in certain age groups, and possibly through a better understanding of the influence that psycho-social factors may have on youngsters' risk of becoming smokers. PMID- 8480009 TI - The school leaver medical: an evaluation. AB - The school records of 492 pupils attending routine school leaver medicals were examined retrospectively. Excluding known problems and problems detected by school nurse screening, only 11 new problems were detected which needed treatment (although a further 18 pupils were investigated to exclude potentially serious problems). Selective examination of school leavers by a school doctor with routine screening by a school nurse would appear to be a more efficient use of time than routine medicals. PMID- 8480011 TI - Preventing unintended teenage pregnancies. AB - A review of the literature on unplanned and teenage pregnancies was undertaken for four District Health Authorities. This work was carried out within a national context of increasing conception rates for teenage women aged 16 and under and in the knowledge that pregnant teenagers and their children tend to have poor life chances. The Health of the Nation White Paper has now focused attention on this by the inclusion of a target to reduce pregnancies to under 16-year-old women by half. To achieve this, health authorities need some understanding of the types of services which might be effective. Whilst there is limited evaluative work on the effectiveness of services for young people in this country, international comparisons suggest that some methods for reducing unintended teenage pregnancies may be more effective than others. The specific service issues identified are the need for advice and support pre-conceptually, during pregnancy and after abortion/birth; the need for easier access to contraception; the need for improved information on risky behaviour--particularly relating to pregnancy, sexually transmitted diseases, HIV/AIDS and substance abuse, and the need for improved medical and social care for pregnant teenage women. The most effective approaches for preventing unintended teenage pregnancy would appear to be the development of comprehensive advisory and family planning services, including sex education and the commitment by central and local government to tackle the adverse socio-economic factors which are associated with teenage pregnancy. PMID- 8480012 TI - The UPA score and teenage pregnancy. AB - Teenage motherhood is often said to be the result of deficient contraceptive and abortion services. Using data from the Public Health Common Data Set (PH CDS) we demonstrate two important effects in a Regional Health Authority: higher rates of conception are related to a live birth rather than an abortion pregnancy outcome; District Health Authorities (DHAs) with high underprivileged area scores (UPA) are more likely to have high rates of conception in the teenage years than those districts with low scores. PMID- 8480013 TI - Routine weighing of infants. PMID- 8480014 TI - The Tomlinson Report. PMID- 8480015 TI - Public health aspects of the war in Yugoslavia. PMID- 8480016 TI - Measles epidemics in Kerman City, Iran. AB - In early 1990 an outbreak of measles occurred in Kerman City (population 257,284), Iran. Overall 745 cases were identified, four of whom died (case fatality ratio was 5.4 per thousand). Illness was limited, primarily, to children below 15 years of age: 166 (22.3%) cases were in children under five years, 573 (77%) in those aged between five and 14 years and six (0.8%) were above 15 years of age. The age of the cases ranged from 5 months to 35 years. The age-specific attack rates were 3.9, 1.8, 7.3 and 2.8 per 1,000 for children under 1, 1-4, 5-9 and 10-14 years of age respectively. Overall 14 (1.9%) children with measles were hospitalized for severe complications which consisted mainly of pneumonia, otitis and gastroenteritis. Based on 745 cases with available immunization records, vaccine efficacy was calculated at 88% indicating a slight problem with the cold chain or vaccine. The outbreak was primarily related to low immunization coverage during the last 10 years and indicates the need to improve vaccine coverage with the AIK-C existing vaccine. It also highlights the urgent need for an effective single-dose measles vaccine (Edmondson-Zagreb) for children below nine months of age. PMID- 8480017 TI - Falls among elderly nursing home residents. AB - The purpose of this study was to measure the rate of falls and to identify the causes, consequences and opportunities for preventing falls among 796 permanent residents of a nursing home. Altogether 377 falls were reported among 207 residents during the study period. The most important association discovered was that between impaired visual acuity and falls. In addition, 49% of the fallers suffered from severe and 19% from mild dementia. In the group of demented subjects it was impossible to assess visual acuity in 30% of the fallers as the subjects were unable to fixate at request. This finding may be one explanation for the increased incidence of falls in demented subjects. We conclude that the high number of subjects suffering from dementia among institutionalized elderly limits the possibility of training in prevention. The main emphasis in prevention of falls in institutions should be in proper design of the environment, including the visual environment. PMID- 8480018 TI - Is there consensus on the placement of older adults? AB - In implementing Caring for People, local authorities and health authorities must decide the most appropriate source of provision of long-stay residential care for older adults. A review of the planning and funding arrangements introduced by Caring for People was conducted, referenced by professional opinion, to find how far a consensus on the above could be achieved. PMID- 8480019 TI - [Postmortem high-resolution computed tomography of the lung. Radiologic morphologic correlations]. AB - To establish precise correlations between high-resolution computed tomography (CT) and normal pulmonary anatomy and pulmonary pathology, 49 lungs affected by different diseases were analysed. Post-mortem high-resolution CT scans were compared with the corresponding macroscopic and microscopic pathological findings. For scanning, lungs were inflated and fixed, which avoided any decrease in the structural resolution of pulmonary parenchyma and allowed a topographically exact correlation between CT appearances and morphological changes. After demonstration of the structural details relevant for CT in normal pulmonary parenchyma, an attempt is made to establish the morphological basis of the following CT phenomena: thickening of interlobular septae, increase in pulmonary translucency, consolidation of the non-nodular alveolar and of the nodular type, and changes in the pleural region. Although CT findings in pulmonary lesions are mainly non-specific, knowledge of the corresponding morphological basis is helpful in diagnostic evaluation. PMID- 8480020 TI - [Functional HR-CT of the lung. Experimental studies of the pulmonary vascular and airway reactions]. AB - We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 microns and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 microns through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol induced bronchoconstriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualizes adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method. PMID- 8480021 TI - [Computed tomography in noninfectious interstitial lung diseases]. AB - Computed tomography is a well-established imaging technique for the assessment of non-infectious interstitial pulmonary disease. Compared with the conventional chest radiograph it is characterized by a higher degree of sensitivity and specificity, particularly when a high-resolution technique is implemented. Because of its superior correlation with the morphological characteristics in specific diseases, it plays an important role if the histological diagnosis is doubtful and also in patients with clinical features suggestive of pulmonary disease in the presence of a normal chest film. This article describes the limitations of the conventional chest radiograph and the advantages of pulmonary computed tomography. Typical CT findings in different interstitial diseases are illustrated, and their value is discussed in comparison with the plain radiograph. PMID- 8480022 TI - [High-resolution computed tomography of the lung in young patients with cystic fibrosis]. AB - In a prospective study we proved the value of high-resolution computed tomography (HRCT) and the CT scoring system developed by Stiglbauer et al. on 47 young patients suffering from cystic fibrosis (CF) (median age: 10.1 years). The most frequent pulmonary finding was bronchial wall thickening (BWT) in 43 patients (94.6%), followed by bronchiectasis (BE) in 36 patients (79.2%). A less frequent finding was ill-defined patchy consolidation (39.6%). We found an almost even distribution of BWT and BE in the upper and lower lobes of the lung. These two findings were scored according to their severity and extent. The maximum possible score for BWT and BE was 72 in a single patient. For both the overall score was 19.9 +/- 11.1. A statistically significant correlation of the CT scoring system with the lung function tests FEV1/FVC (P = 0.03) and MEF50 (P = 0.02) was found. The results of HRCT and the CT scoring system were shown to be valuable methods in the assessment of pulmonary changes, in young patients suffering from CF. PMID- 8480023 TI - [High-resolution computed tomography (HR-CT) of the lung following lung transplantation]. AB - We report our high-resolution computed tomography (HRCT) and conventional CT findings after lung transplantation in 20 patients. Sixty-four examinations were performed 7-511 days after transplantation. The radiological observations were then correlated with the clinical results. The pathological findings in the early postoperative phase were pleural effusion, edema, and pulmonary consolidation. The HRCT findings associated with acute rejection were nonspecific. Dilation and thickening of the walls of the peripheral bronchi is a common, but non-specific feature in bronchiolitis obliterans. The manifestations of posttransplant lymphoproliferative disorder are discussed in two patients. PMID- 8480024 TI - [Magnetic resonance tomographic findings in cardiac tumors]. AB - After ultrasound, magnetic resonance imaging (MRI) is the second noninvasive powerful method of examining the heart. The findings in 9 patients with cardiac tumors are reported, who were examined by means of MRI: There was little variance in the MRI signal behavior (with only one exception), although the tumor population examined was very heterogeneous. The MRI techniques used (T1-weighted spin echo, steady-state gradient echo) seem to allow no better tumor specification than ultrasound. Wince multiplanar reconstruction is possible with MRI, tumor size, localization, and the borders of the cardiac neoplasms can be depicted. The cine technique provides dynamic information. In addition, this method allows reliable discrimination between the flow effects and true space occupying lesions. PMID- 8480025 TI - [A malignant bone tumor?]. PMID- 8480026 TI - Regulation of serotonin synthesis. PMID- 8480027 TI - Short-term control of GABA synthesis in brain. PMID- 8480028 TI - Short-term control of the synthesis of acetylcholine. PMID- 8480029 TI - [Chronic idiopathic periostosis]. PMID- 8480030 TI - Isolated unilateral clavicular hypoplasia. A case report. PMID- 8480031 TI - [A rare case of congenital fusion between the scaphoid and capitatum]. PMID- 8480032 TI - [Muscular hydatidosis. The echographic, computed tomographic and magnetic resonance aspects. Apropos a case]. PMID- 8480033 TI - [Cerebral ischemic lesions following tuberculous meningitis. A case report]. PMID- 8480034 TI - [Recklinghausen's neurofibromatosis. A report of a case characterized by extensive thoracic and abdominal locations]. PMID- 8480036 TI - [A case of suspected pulmonary alveolar microlithiasis]. PMID- 8480035 TI - [Magnetic resonance in the diagnosis of lesions of the carpal triangular fibrocartilage. The experience with 49 patients with chronic pain at the wrist]. AB - In order to evaluate the diagnostic capabilities of MR Imaging in defining triangular fibrocartilage (TFC) lesions, 49 selected patients--21 with rheumatoid arthritis, 13 with traumatic injury and 15 with wrist fracture--presenting chronic wrist pain were examined with MR Imaging. The wrists of 12 healthy subjects were also studied as a control group. MR examinations were performed by means of a superconductive 1.0 T unit (Magnetom-Siemens); SE and GE T1- and T2 weighted pulse sequences were employed to acquire images of the wrists on the coronal, axial and, if necessary, sagittal planes. The results showed peripheral TFC tears in 10 cases, central TFC lesions in 12 cases and TFC lesions with collateral insertion involvement in 9 cases. In 4 patients focal thickening of TFC without disruption was observed. The correct diagnosis was made in all the 19 surgically verified cases. Our experience confirms the clinical value of MR Imaging in the evaluation of TFC lesions in patients with chronic ulnar pain syndrome. PMID- 8480037 TI - [Rhodococcus equi pulmonitis in HIV+. A review of the literature and a case report]. PMID- 8480038 TI - [A pseudoaneurysm of the right phrenic artery treated by preoperative percutaneous embolization]. PMID- 8480039 TI - [The echographic diagnosis of portal venous gas. 3 cases]. PMID- 8480040 TI - [A rare case of a voluminous aneurysm of the hepatic artery. A computed tomographic, echo-Doppler and arteriographic study]. PMID- 8480041 TI - [The magnetic resonance aspects of cystic lymphangiomatosis. Apropos a case]. PMID- 8480042 TI - [A volumetric increase in the submandibular glands due to an organic iodate contrast medium. A case report]. PMID- 8480043 TI - [Desmoid tumor of the anterior abdominal wall. A case report]. PMID- 8480044 TI - [The disease of beta 2-amyloid deposition in the differential diagnosis of juxta articular subchondral geode lesions]. AB - Beta-2 amyloidosis deposition is a new type of amyloidosis recently observed in long-term hemodialysis patients. One of the major osteoarticular complications of this disease is the appearance of subchondral bone cysts. In this paper the radiologic features of such radiolucencies are described and the criteria are outlined of the differential diagnosis from the geodes found in other arthropathies or para-physiologic conditions. The importance of the status of the joint space is stressed: on the basis of its patterns, arthropathies may be grouped as follows: inhomogeneous space narrowing in degenerative arthritis; homogeneous space narrowing in inflammatory arthritis; normal or nearly normal joint space if there is no/not-prevalent involvement of articular cartilage. PMID- 8480045 TI - [Osteoporosis and the thalassemia "trait"]. AB - The authors evaluated the prevalence of the thalassemia trait in a general population affected with femoral neck fractures. Our research was aimed at assessing whether hemoglobinopathy might affect osteoporosis, which is responsible for femoral fractures. Two hundred and thirty-eight patients admitted to St. Anna Hospital, Ferrara, for proximal femoral fractures, were retrospectively studied. The patients were 68 males and 170 females, aged 58 to 83 years (mean age: 70.4 years). The thalassemia trait was seen in 11.76% of cases, versus in 7-8% of the general population. The high prevalence of heterozygous beta-thalassemic subjects probably means that the beta-thalassemia condition is a further "variable" which is responsible for the more frequent occurrence of fractures of the proximal femur and is certainly related to an osteopenic condition much more severe than usual. PMID- 8480046 TI - [Hemophilic arthropathy: echography and radiology]. AB - Our experience is reported with the combined use of radiology and US in the study of 210 joints of hemophilic patients. The study was carried out considering that in hemophilia the classification of the grades of disease generally relies upon X ray findings which, although reliable in the advanced stages of the disease, appear inadequate in the early stages. In fact, synovial hypertrophy, cartilage erosions and initial subchondral cysts are most often missed on X-ray films. In the examined cases, US was employed to evaluate: 1) the degree of synovial hypertrophy, 2) the status of the explorable cartilage, 3) the presence of effusions and 4) the status of bone linings--whenever erosions, even of minimal extent, were suspected, X-rays were always performed and the results employed as the reference standard. The examined joints did not exhibit the same grade of involvement: the knee, elbow and ankle had advanced arthropathy in 85% of cases, corresponding to > or = 7 according to Pettersson score. On the contrary, the shoulder and hip were found to be equally involved either by initial (Pettersson score: 0-6) or by advanced arthropathy (Pettersson score: > or = 7). Moreover, in nearly 10% of the cases, hemarthrosis was found which showed no correlation with the grade of joint involvement. Our results indicate that: 1) US appears very useful in the early stages of the disease when the X-ray picture is negative or poorly significant. The demonstration of early alterations is useful mainly in those cases in whom synoviectomy is considered (for prevention); the latter is useful only if performed before cartilage erosion appear; 2) US appears equally useful in hemarthrosis cases, especially in those of limited extent in which the clinical therapeutic management may be difficult; 3) US appears unnecessary in the cases of advanced arthropathy in which X-rays serve as the reference standard. PMID- 8480047 TI - [Magnetic resonance angiography in the study of neoplastic cerebral pathology]. AB - To date, magnetic resonance angiography (MRA) has been used in neuroradiology mainly to study vascular malformations and atherosclerotic changes of the carotid bifurcation. Our study was aimed at investigating the role of MRA with the time of-flight technique in the study of intracranial neoplasms; a superconductive 1.5 T magnet was used, and FLASH and FISP 2D and 3D pulse sequences were acquired before and after Gd-DTPA administration. Fifty-five MRA examinations were performed. Our series consists in 32 meningiomas, 14 glial tumors, 3 hypophysis adenomas, 2 metastases, 1 NF2, 2 craniopharyngiomas, 1 lymphoma and 1 rhinopharyngeal carcinoma with intracranial involvement. In 27 patients MRA results were compared with DSA findings. The results showed high agreement relative to indirect angiographic patterns (dislocations, encasement, dural sinuses involvement) and poor accuracy in the demonstration of tumor vascularization (inflow and outflow, vascular neoformation). PMID- 8480048 TI - [Inflammation of the anterior chest wall: its assessment by magnetic resonance]. AB - Magnetic resonance (MR) is the imaging method used to assess primary and secondary inflammatory lesions of the chest wall. Five patients with inflammatory lesions of the anterior chest wall were submitted to MR examinations in order to define the role of this method in both identification and assessment of the extent of tissue involvement. In all the examined patients MR Imaging accurately showed the involved muscle groups and the presence/absence of mediastinitis. MR Imaging easily detected sternal and clavicular osteomyelitis; in one patient only MR failed to detect osteomyelitis of the first rib. The accurate assessment of soft tissue infections enabled us to select the most suitable surgical therapy to reduce esthetic damage. Two cases were restudied after chest wall reconstruction by means of rotated pectoral flaps. In the 2 patients in whom the differential diagnosis between inflammatory lesion and recurrent tumor could not be made by means of MR Imaging, CT-guided needle biopsy was performed. PMID- 8480049 TI - [Nodular lesions simulated on an anthropomorphic thoracic phantom. A comparison between analog and digital images of the thorax]. AB - Aim of this work is to evaluate the diagnostic accuracy of different modalities of digital radiology, compared with conventional radiology, in the detection of lung nodules. Forty images of an anthropomorphic chest phantom, on which simulated nodules had been previously set, were analyzed by 6 radiologists with 4 different viewing modalities: a) conventional radiography; b) photostimulable plates digital radiography; c) photostimulable plates digital image on dedicated monitor; d) conventional radiography digitized with Film Laser Digitizer and viewed on Display Workstation. For each image the radiologists had to transfer on a sketch the site of the detected nodules giving an opinion on their detectability (uncertain-presumable-probable-certain presence) with a 1 to 4 score. The statistical analysis of the results was made using modified ROC curves. No statistically significant difference was found between the areas under a) and c) ROC curves (p = 0.262). A statistically significant difference resulted between the areas under a) and d) ROC curves (p < 0.05) and, particularly, between the a) and b) areas (p < 0.001), in favor of a). PMID- 8480050 TI - [A comparison between traditional mammography and digital with storage phosphors]. AB - Conventional and digital mammographic images obtained with storage phosphors were compared. The digital images were acquired with high-resolution 3rd-generation (HR III) screens and specifically adapted algorithms. The experience was made both on a phantom and in vivo. The phantom study was carried out by comparing conventional with digital radiographs acquired with: a) same kV (28) and same mAs; b) same kV (24) and same mAs; c) 28 kV with 30% mAs reduction, in digital images only. The results obtained upon counting the amount of recognizable details per image demonstrated slight loss of information in digital radiographs only when mAs was reduced by 30%. Two hundred patients were studied; they were divided into four groups according to the type of breast (medium inherent contrast or solid breast) and to exposure factors. After conventional mammography, an additional digital radiograph was performed using one of the three techniques previously employed on the phantom. Separately, 10 ductogalactographies and 10 magnification radiographs of microcalcifications were compared; the same exposure factors were used in these images too. The radiographs were viewed by three expert mammographic radiologists; contrast quality and spatial resolution were investigated and a score was given to each image on a 3-grade scale (insufficient, sufficient, good). The comparison of the mean values obtained showed higher contrast and better enhancement of nodular lesions on digital images, on which, however, the depiction of microcalcifications was worse than on conventional radiographs, especially with lower radiation doses, even though the number of detected microcalcifications was the same. PMID- 8480051 TI - [The evaluation of a digital system for the automatic analysis of the density of abdominal radiograms]. AB - This paper reports the results of the evaluation of an automatic system developed to analyze radiographic densities. This system, called RADEN, has been implemented at the Institute for Information Processing of the Italian National Research Council in Pisa. Forty-three pairs of abdominal X-ray films were obtained before and after the administration of ionic iodate contrast medium (i.i.c.m.) during urographic examinations. The 86 X-ray films were acquired and digitized using a computer-controlled optoelectronic device with a sampling step ranging 125 microns to 250 microns. The resulting images were arrays of 512 x 512 pixels, each one quantified on a byte (256 gray levels). The computing system included a high-performance personal computer equipped with a video RAM board having built-in facilities for image processing and with an optical disk to archive the images. Automatic and semi-automatic procedures were developed to segment, recognize and classify the images and to characterize three homogeneous regions--i.e., bone, water and air. The output data were compared with the area values of the air densities computed directly on the X-ray films by a radiologist. Furthermore, both data sets were compared with the scores given in a blind study by four observers. The subsequent statistic analysis showed the increase in air density areas after i.i.c.m. administration and the applicability of the implemented system to the automatic examination of abdominal radiographic densities. The results encourage to believe that the proposed approach could be employed as a first step for the development of quite a more complex system oriented to X-ray image understanding and to assisted diagnosis. PMID- 8480052 TI - Spondylo-metaphyseal dysplasia corner fracture type (a cautionary tale). AB - Spondylo-metaphyseal dysplasia Sutcliffe type is a rare disease characterised by oval vertebral bodies, coxa vara and metaphyseal irregularities. It was named spondylo-metaphyseal dysplasia corner fracture type by Langer et al. as corner fractures are a constant feature later in life. We report 3 further cases of spondylo-metaphyseal dysplasia Sutcliffe type; one without coxa vara and 2 bone dysplasias with distinctive radiographic features--different from spondylo metaphyseal dysplasia Sutcliffe type, for diagnosis. Both of the latter showed corner fractures. Corner fractures are a characteristic but not diagnostic feature of spondylo-metaphyseal dysplasia Sutcliffe type. PMID- 8480053 TI - [The pancreas in diabetes mellitus. The echographic aspects]. AB - Forty patients with diabetes mellitus (25 with insulin-dependent and 15 with non insulin dependent diabetes) were studied by means of US in order to evaluate possible volumetric alterations in the pancreas and their eventual progression over time. Thirty healthy subjects were also studied as a control group. The following variables were recorded: thickness of the head, body and tail of the pancreas and area of its head. The patients were also divided into 5 groups according to the age of diabetes (< 1, > 1, > 7, > 14, > 21 years). The results showed 25 IDDM patients to exhibit significant reduction in these variables relative to controls (p < = 0.01), especially in the body (average reduction 40%) and tail (average reduction -20%) of the pancreas. NIDDM patients exhibited non-significant reductions in pancreatic size. The study of the 5 groups of IDDM patients, divided according to the duration of diabetes, revealed all pancreatic variables to reduce more than in controls within a year since diagnosis, to exhibit relative increase during the next 7 years and finally to reduce again in the following years. These results show that anatomic damage to the pancreas occurs within the first year of diabetes. Moreover, IDDM was seen to alter the normal proportions among the single anatomic structures forming the pancreas, especially relative to two anatomic ratios--i.e., head/body and tail/body pancreatic thickness. The relative values in IDDM patients were markedly higher than those in controls (p < 0.001). The patients were again divided into 5 groups according to the age of diabetes: the values of the above ratios in the course of diabetes greatly differed from those observed in controls--i.e., they increased within the first year of diabetes, were steady during the next 7 years, and returned to normal values after 21 years of diabetes, which meant the return to the normal anatomic ratios among the three parts of the pancreas. PMID- 8480054 TI - [The echographic and computed tomographic diagnosis of polysplenia]. AB - Polysplenia syndrome is a malformation with impaired visceral lateralization; it consists in the incomplete development of the spleen which is replaced by two or more splenules (1-3 cm phi). This malformation is often associated with other anomalies and is more frequently seen in situs inversus and situs ambiguus. On the basis of their findings in 3 cases, the authors describe the main US and radiographic patterns of polysplenia syndrome, that is: polysplenia syndrome associated with situs solitus (several splenules where the spleen should be, without other anomalies); polysplenia syndrome associated with situs ambiguus (splenules in the right hypochondrium with such anomalies as "umbrella-like" liver and the absence of the hepatic segment of the inferior vena cava and enlargement of both azygos and hemiazygos veins); polysplenia syndrome associated with situs viscerum inversus (right-sided splenules, with transposition of abdominal and thoracic organs). The splenules exhibit the same echogenicity as the liver; when situs viscerum ambiguus is present. US patterns of splenuli are equivocal and may mimic liver metastases. On the contrary, CT allows better demonstration of both the anomaly and the associated malformations. PMID- 8480055 TI - [Echography applied in dermatologic diseases. A comparative preliminary study of the use of high-frequency transducers]. AB - Ultrasonography (US) was first used in dermatology in 1979. During the last few years, US has evolved thanks to technological progress and its use has been on the increase, in dermatology, to study both localized and diffuse skin diseases. In this paper, the authors review and compare the results obtained with a 20 MHz transducer with those obtained with 7.5 MHz and 10 MHz transducers in the study of skin alterations. Three parameters were considered: lesion identification, spatial evaluation and US structure. Fifty-eight cases of localized and 48 of diffuse skin diseases were examined. The localized forms were benign in nature in 18 patients (3 nevi, 2 seborrheic keratoses, 3 ulcus cruris cases, 6 sebaceous and 2 liquid cysts). The other 40 patients had malignant neoplastic lesions (16 epitheliomas, 13 primitive melanomas, 1 metastatic melanoma, 8 lymphomas and 2 Kaposi's sarcomas). The 48 cases of diffuse conditions included 27 systemic sclerosis, 18 psoriasis and 3 lichen planus cases. The comparative analysis of the results obtained using the different types of transducers in the study of localized dermatoses showed no differences in lesion identification and in the depiction of their US features. On the other hand, the 20 MHz transducer was much more accurate than the others as regards the spatial evaluation of the lesions measurable in millimeters, whereas it poorly demonstrated the lesions > 1.5 cm. However, only the 20 MHz transducer could demonstrate the US features of diffuse conditions. PMID- 8480056 TI - [Computed tomography in the follow-up of patients nephrectomized for adenocarcinoma]. AB - A retrospective study was carried out of 159 CT examinations acquired in 64 patients who underwent unilateral nephrectomy for renal-cell carcinoma (34 in the left-hand side and 30 in the right-hand side). Thirty-nine patients were examined twice in the three years following nephrectomy; 25 were examined three or more times over a 5-year period after nephrectomy. Acute or chronic inflammatory disease was demonstrated in 6 patients (4 abscesses were detected by means of clinico-radiologic signs and 2 by means of cytology after CT-guided needle biopsy). Twenty patients had local recurrences 2-7 cm phi: in 17 of them the diagnosis was confirmed by CT-guided percutaneous FNAB; 15 patients had liver metastases, in 3 of them associated with local recurrences; 26 patients were free of both local recurrences and distant metastases. The authors analyze the value of CT in the definition of post-nephrectomy anatomic alterations, in the early detection and staging of local recurrences, and in the differentiation between postoperative fibrosis and complications. Moreover, the value is stressed of CT guided FNAB of suspicious lesions. Our study suggests the value of a methodical CT follow-up of asymptomatic post-nephrectomy patients. CT immediately after surgery is also recommended to serve as a baseline reference for subsequent examinations. In our series, CT was accurate in the early detection of both local recurrences and distant solitary metastases. PMID- 8480057 TI - [The stationary grid in mammography: its clinical evaluation]. PMID- 8480058 TI - [Smoking addiction treatment, with nicotine chewing gum, in primary care. Double blind study]. AB - BASIS: Study of the efficacy of nicotine chewing gum in the treatment of smoking addiction in primary health care. METHODS: Three interventions groups are compared. Active group (37): treated with group psychotherapy and nicotine chewing gum; Placebo group (38): Treated exactly as first group, but with placebo chewing gum, and Outpatient Group (31): Individual psychotherapy in an outpatient basis, with nicotine chewing gum. RESULTS: Comparison of results, one year after intervention, between active group (35.1% success) and placebo group (13.2% success) showed the existence of statistically significant differences (p < 0.03). Outpatient group yielded 25.8% success rate, without finding any statistically significant differences in comparison with the active group. CONCLUSIONS: Nicotine chewing gum can be an effective support in the treatment of smoking addiction, in primary health care, in certain smokers, assuming that this treatment is accompanied with individual or group psychotherapy follow up, which reinforces the behavior and prevents relapses. PMID- 8480059 TI - [Diabetes mellitus in the elderly: a study on its clinical presentation, C peptide reserve, and immunogenetic markers of insulin dependence]. AB - In order to evaluate clinical presentation and to determinate classification criteria of type 1 diabetes in the elderly, we carried out a study in 258 diabetic patients more than 60 years old of which 100 used insulin by failure to oral hypoglycemic agents (OHA). The prevalence of ischemic cardiovascular disease was 36%, peripheral vascular disease 34% and stroke 30%. Non-proliferative retinopathy 47%, nephropathy 16% and peripheral neuropathy 37%. Cardiovascular risk factors as obesity (36%), hypertension (33%) and hypercholesterolemia (12%) were evaluated. The average duration of diabetes was 20 years. Post-glucagon C Peptide, HLA-DR antigens and islet cell antibodies (ICA), were measured in 75 older diabetic patients on treatment of which 24 used insulin, 11 diet and 40 OHA. Older patients on treatment with insulin had longer duration of disease, less obesity, low level basal of C-Peptide and a low response to post glucagon C Peptide (0.94 +/- 0.5 pmol/ml) compared with patients on diet (1.8 +/- 0.9 pmol/ml) and OHA (1.8 +/- 0.8 pmol/ml). Older diabetics on insulin therapy had a greater frequency of HLA-DR3 (42%) and HLA-DR4 (21%) than other older diabetics. The ICA was negative in most patients. This study shows the high prevalence of macrovascular and microvascular disease in elderly patients with diabetes mellitus and that the most reliable parameter in classifying type 1 (insulin dependent) diabetes is the measurement of basal and post-glucagon C-Peptide. HLA DR specific markers can be used with this parameter because their expression is partly shared. This approach appears useful in the older diabetic patients to help classify diabetes and its management. PMID- 8480060 TI - [Respiratory function tests. Differences between smokers and non-smokers. Effects of withdrawal]. AB - The purpose of this study is to determine the characteristics of spirometric performance in a group of smokers and to carry out a prospective study of the changes in ventilatory lung function after smoking withdrawal. The ventilatory lung function was studied in 90 smokers and 30 non-smokers. Afterwards the smokers were included in smoking withdrawal program. One year later, the ventilatory function tests were repeated in those individuals who were able to stop smoking. Respiratory function tests were likewise repeated in 10 subjects chosen randomly among those who were not able to stop smoking. The initial study of the ventilatory lung function showed that smokers had significantly lower values of FVC (p < 0.001), FEV1 (p < 0.001), FEVC1/FVC (p < 0.001), FEF25-75 (p < 0.01 and PEF (p < 0.01) compared to non-smokers. Likewise smokers also had a statistically significant higher prevalence rate of obstructive pulmonary disease (p < 0.001). Ventilatory function studies performed one year after smoking withdrawal on those who were able to stop smoking showed a significant improvement of respiratory function parameters compared to studies done one year before. There was also a significant decrease in the prevalence and severity of obstructive pulmonary disease. No differences were observed in the ventilatory function tests performed on the ten subjects who did not stop smoking. From these data we suggest that tobacco consumption produces obstruction of the airways that can be reverted, at least in part, after smoking withdrawal. PMID- 8480061 TI - [Spontaneous tendinous rupture in systemic lupus erythematosus. Presentation of 2 cases]. AB - Spontaneous tendinous breakage is a rare complication in patients with systemic erythematous lupus. Bilateral tendinous breakage is an exceptional phenomena. Two cases of bilateral spontaneous breakage are discussed, one achillea, the other patellar, its frequency is compared in the scientific literature with the one found in the patients at our center. Magnetic Resonance usefulness is underlined to confirm the diagnosis of tendinous breakage. PMID- 8480062 TI - [Secondary arterial hypertension in type I neurofibromatosis (NF-1). Findings in 6 patients]. AB - With the aim to analyze the association of Type I Neurofibromatosis with secondary arterial hypertension, a retrospective study has been performed on 36 patients, diagnosed of pheochromocytoma (n = 12) and/or renal artery stenosis (n = 25), finding in 6 of them diagnostic criteria of Type I neurofibromatosis, of these 4 showed pheochromocytoma, 1 renal artery stenosis and 1 pheochromocytoma plus renal artery stenosis. CAT and angiography were the best diagnostic imaging methods to confirm clinic and biological suspicion of adrenal tumor of renal artery stenosis. It is recommended the systematized study of patients with NF-1 together with their relatives who phenotypically show some illness stigma, or with arterial hypertension resistant to conventional treatment. PMID- 8480063 TI - [Auditory evoked potentials and magnetic resonance in the diagnosis and follow-up of central pontine myelinolysis]. AB - We report the case of a woman who developed central pontine myelinolysis in spite of gradual correction of hyponatremia. The good clinical evolution as well as the influence of rapid correction of serum sodium concentration in the unfolding of this rare condition are discussed. Several diagnostic procedures, mainly auditory evoked responses and magnetic resonance imaging are also analysed. We remark the particular interest of the auditory-evoked responses in the attestation of an eventual remyelination. PMID- 8480064 TI - [Specifications on the lecithin/sphingomyelin ratio (L/S). Updated review]. AB - We review the lecithin/sphingomyelin ratio (L/E) studying the amniotic fluid to value the fetal lung maturity. We compare him with others biological parameters. We consider the modifications arising across pregnancy and in different diseases as well as the factors influencing its results. PMID- 8480065 TI - [Rectovaginal fistula as presentation form of Crohn disease]. PMID- 8480066 TI - [Favorable course of cerebral toxoplasmosis treated with doxycycline and pyrimethamine]. PMID- 8480067 TI - [Primary duodenal adenocarcinoma. Report of a new case]. PMID- 8480068 TI - [Clinical resolution of a suspected thyroid nodule]. PMID- 8480069 TI - [Parkinsonism induced by metoclopramide]. PMID- 8480070 TI - [Mononucleosis syndrome in a patient with varicella]. PMID- 8480071 TI - [Sweet's syndrome as presentation form of hairy cell leukemia]. PMID- 8480072 TI - [Native valve endocarditis caused by Staphylococcus epidermidis]. PMID- 8480073 TI - [Herpes zoster involving multiple cranial nerves]. PMID- 8480074 TI - Developmental retardation of the Japanese quail embryo under the influence of dexamethasone. AB - Cultured Japanese quail embryos were treated with various doses of dexamethasone on day 2 and in part also on day 5. The treatment lead to a significant delay of development. This was demonstrated by means of developmental (growth rate, developmental stage), histological and metabolic (excreted uric acid, protein synthesis) parameters. The effect was intensified when the agent was administered into the subembryonic liquid instead of the albumen. This is due to the fact that a higher dilution is expected when the agent is deposited into the albumen. In conclusion Japanese quail embryos respond to exogenous glucocorticoids, at a very early stage of development and at a comparatively low concentration with a depression of development. PMID- 8480075 TI - Cellular sensitivity to native type IV collagen in primary biliary cirrhosis. AB - We examined 60 patients with various chronic liver diseases for cellular sensitivity to native human type I and IV collagens using an in vitro leucocyte migration inhibition test. Mononuclear cells from 7 (33%) of 21 patients with chronic active hepatitis, 14 (52%) of 27 patients with liver cirrhosis and 11 (92%) of 12 patients with primary biliary cirrhosis exhibited cellular sensitivity to type IV collagen, although cells from almost all patients responded to type I collagen. None except one for type I collagen of 25 normal controls showed positive response to both collagens. In chronic active hepatitis and liver cirrhosis, cellular sensitivity to type IV collagen was significantly lower than to type I collagen (p < 0.01). Patients with primary biliary cirrhosis showed significantly higher cellular sensitivity to type IV collagen when compared to patients with other chronic liver diseases (p < 0.01). Cellular sensitivity to type IV collagen was significantly correlated with serum levels of the 7S domain of type IV collagen in all 85 subjects (r = +0.462, p < 0.001). These findings suggest that cellular sensitivity to type IV collagen as well as to type I collagen exists in chronic liver disease, especially in primary biliary cirrhosis, and may reflect the accelerated metabolism of the perisinusoidal and peribiliary basement membranes. PMID- 8480076 TI - Antiproliferative and antimetastatic effects of gossypol on Dunning prostate cell bearing Copenhagen rats. AB - Gossypol, a polyphenolic aldehyde naturally present in cottonseed, has long been recognized as a male contraceptive and recently as a potential anticancer agent. Our study used a rodent model to evaluate gossypol's potential for the treatment of human prostatic carcinoma. Two-month-old Copenhagen male rats received subcutaneous implants of a subpassage of MAT-LyLu prostatic cancer line, a highly metastatic, androgen-independent Dunning prostate tumor subline that specifically metastasizes to lymph nodes and lungs of recipients. After 2 weeks of gossypol treatment (0 or 12.5 mg/kg B.W./day S.C.) initiated immediately after transplantation, the rats were sacrificed and evaluated for prostate tumor growth and metastasis. Testosterone and gossypol levels in tumor tissue and various reproductive organs and serum potassium level were measured by radioimmunoassay (RIA), high pressure liquid chromatography (HPLC) and atomic emission spectroscopy (AES), respectively. Gossypol-treated rats exhibited weight reductions in developed MAT-LyLu prostate tumor mass and prostate of 24% (p < 0.05) and 31% (p < 0.05), respectively; whereas testicular and epididymal weights were not significantly affected. Few metastases (20%) were observed in either lymph nodes or lungs of gossypol-treated recipients. The control rats, however, had a much higher rate of lung (60%) and lymph node metastasis (40%). Testicular testosterone levels, as measured by RIA, were significantly lower in gossypol treated rats than in controls (p < 0.05), but serum testosterone levels were not different. Extractable gossypol content in the prostate tumor, as measured by HPLC, reached 19.67 ng/gm and was 1.28 times higher than in liver, 1.98 times higher than in testes, but was 3.3% of that in prostate. Moreover, serum had the highest gossypol content (10.7 micrograms/ml). Serum potassium levels, as measured by AES, were significantly higher in gossypol-treated individuals than controls (p < 0.05). Our results indicate for the first time that gossypol has antiproliferative and antimetastatic effects on MAT-LyLu prostate cancer cells and can be explored as a potential therapeutic agent for androgen-independent human prostatic carcinoma. PMID- 8480077 TI - Theophylline increases pyridoxal kinase activity independently from vitamin B6 nutritional status. AB - Asthmatics treated with theophylline, a potent inhibitor of pyridoxal kinase and therefore a vitamin B6 antagonist, demonstrated a significant correlation (r = 0.71; p < 0.001) between drug plasma levels and erythrocyte pyridoxal kinase activities. A cross-over, placebo controlled study was completed on 15 healthy volunteers to investigate the mechanism by which theophylline induces pyridoxal kinase activity. The subjects were supplemented with vitamin B6 or placebo for two weeks before theophylline therapy was started. Vitamin B6 supplementation resulted in a four-fold increase in circulating pyridoxal 5'-phosphate levels, while placebo had no effect. When theophylline therapy was commenced, erythrocyte pyridoxal kinase activities increased significantly (p < 0.001) irrespective of whether vitamin B6 or placebo was supplemented. It is concluded that a depressed vitamin B6 status is not responsible for higher erythrocyte pyridoxal kinase activities encountered during theophylline therapy, but that the drug is directly responsible for elevated enzyme levels. PMID- 8480078 TI - Effects of felbamate and other anticonvulsant drugs in two models of status epilepticus in the rat. AB - Felbamate was compared with several antiepileptic drugs for protective effects in two rat models of status epilepticus. Felbamate was ten times more potent against pilocarpine-induced seizures in lithium-treated rats than in lithium-free animals. Diazepam, valproate and phenobarbital were effective in both the high dose pilocarpine and lithium-pilocarpine models. On the other hand, phenytoin was ineffective in both models, whereas carbamazepine displayed protective effects only in the lithium-pilocarpine model. PMID- 8480079 TI - In vitro metabolism of cyanohydroxybutene: formation of a glutathione-S transferase catalyzed product. AB - The pancreatotoxin cyanohydroxybutene (CHB) causes a significant and prolonged elevation in glutathione (GSH) in liver and pancreas (Wallig and Jeffery, 1990). Here we report that urinary thiols also increase. This suggests that CHB may react with GSH, either directly or following phase I oxidation, to form an adduct, which is further metabolized to the corresponding mercapturic acid for urinary excretion. Metabolism of CHB by hepatic mixed function oxidase and cytosolic alcohol dehydrogenase enzymes was evaluated by monitoring microsomal NADPH consumption and alcohol dehydrogenase-dependent NADH generation, respectively. There was no apparent increase in the rate of microsomal NADPH consumption or alcohol dehydrogenase-dependent NADH generation in the presence of CHB. To evaluate in vitro formation of a glutathione-S-transferase (GST) catalyzed adduct, [3H-glycyl]-GSH and [14C-cyano]-CHB were incubated at 37 degrees C for 1 h, with or without GST. Dinitrophenol derivatization and high performance liquid chromatographic (HPLC) analysis (Farris & Reed, 1987) revealed no double-labeled peaks, suggesting that no stable conjugate was formed. However a tritiated product, not present in control samples, and with an identical retention time to cysteinyl-glycine (cys-gly) was formed. In addition, the product has a fast atom bombardment mass-spectrum consistent with cys-gly. These results suggest that while CHB may not undergo phase I oxidation, in the presence of CHB, GSH may break down to form cys-gly. A mechanism for CHB-dependent breakdown of GSH to cys-gly is proposed, and the pharmacological implications of this finding are discussed. PMID- 8480080 TI - Antiinflammatory activity of aminoketone derivatives of 2,4-disubstituted thiazoles. AB - A group of nine aminoketones, 2,4-disubstituted thiazole derivatives were tested in vivo in order to evaluate their biological activity. Antiinflammatory activity was studied by means of the carrageenin-induced mouse paw edema. Writhing induced by acetic acid in rats used to evaluate the analgesic activity. The results are discussed from the view of structure activity relationship. PMID- 8480081 TI - Antipyrine concentrations in liver and blood monitored by microdialysis of unrestrained conscious rats. AB - A newly developed microdialysis probe for measurement of drugs in unrestrained, conscious animals was used for quantitation of antipyrine in liver and blood of rats. Microdialysis probe were implanted in the liver and right jugular vein of rats; antipyrine was then administered at a dose of 50 mg/kg i.p. The concentration of antipyrine was determined in the fluid from the two probes and compared with measurement made on blood drawn from the left jugular vein. The elimination half lives in serum, blood dialysate and hepatic dialysate were 2.24 +/- 0.09, 2.06 +/- 0.31 and 2.10 +/- 0.32 hrs, respectively; there were not significantly different statistically. The concentration of Na+, K+ and Cl- in the hepatic dialysate was stable at least for up to 12 hrs in anesthetized rats. In unrestrained, conscious animals these electrolytes were stable in hepatic dialysate for at least 48 hrs. Therefore, the microprobe should be useful for analysis of drugs in extra cellular fluids of rats liver for up to 48 hrs. These studies suggest that this microdialysis technique by employing the newly developed probe will be useful in many studies on pharmacokinetics and drug metabolism in the organ. PMID- 8480082 TI - Evaluation of 5-hydroxytryptamine concentration in portal vein measured by microdialysis. AB - Free 5-hydroxytryptamine (5-HT) concentration in the portal vein was monitored in anesthetized rats using microdialysis. The 5-hydroxytryptamine metabolite 5 hydroxyindoleacetic acid (5-HIAA) was also measured. Concentration of 5-HT in the portal vein decreased gradually after insertion of a microdialysis probe but fluctuated markedly throughout the entire perfusion, whereas 5-HIAA values did not fluctuated in the same manner. An electron microscopic study of the probe membrane after dialysis showed platelet adhesion and aggregation on part of the membrane. In contrast, 5-HT concentration measured by puncture and direct blood sampling of the portal vein did not fluctuate in the same way as that determined by microdialysis. These results suggest that measurement of free 5-HT concentration in the blood by microdialysis might be inaccurate due to contamination of 5-HT from adhesion and aggregation of platelets on the probe membrane. PMID- 8480083 TI - Effect of various dietary constituents on gastrointestinal absorption of aluminum from drinking water and diet. AB - The influence of some frequent dietary constituents on gastrointestinal absorption of aluminum from drinking water and diet was investigated in mice. Eight groups of male mice received lactic (57.6 mg/kg/day), tartaric (96 mg/kg/day), gluconic (125.4 mg/kg/day), malic (85.8 mg/kg/day), succinic (75.6 mg/kg/day), ascorbic (112.6 mg/kg/day), citric (124 mg/kg/day), and oxalic (80.6 mg/kg/day) acids in the drinking water for one month. At the end of this period, animals were killed and aluminum concentrations in liver, spleen, kidney, brain, and bone were determined. All the dietary constituents significantly increased the aluminum levels in bone, whereas brain aluminum concentrations were also raised by the intake of lactic, gluconic, malic, citric, and oxalic acids. The levels of aluminum found in spleen were significantly increased by gluconic and ascorbic acids, whereas gluconic and oxalic acids also raised the concentrations of aluminum found in kidneys. Because of the wide presence and consumption of the above dietary constituents, in order to prevent aluminum accumulation and toxicity we suggest a drastic limitation of human exposure to aluminum. PMID- 8480084 TI - Second branchial arch anomalies induced by fluconazole, a bis-triazole antifungal agent, in cultured mouse embryos. AB - The teratogenic potential of the novel bis-triazole antifungal agent fluconazole (F) was investigated on mouse embryos during early organogenesis using the whole embryo culture system. Early somite stage embryos (4-5 somites) were continuously cultured for 48 hours in rat serum added with 0, 25, 50 or 75 micrograms/ml of F. Doses of 50 and 75 micrograms/ml of F significantly (p < 0.001) impaired morphogenesis, resulting in a 83.3% and 91.6% of embryos showing second branchial arch anomalies, respectively. These findings demonstrate that F induces second branchial arch anomalies in cultured mouse conceptuses. Furthermore, these results may suggest an useful model for the study of arches-derived malformations. PMID- 8480085 TI - Differentiation of acute promyelocytic leukemia cell induced by 1,25 dihydroxyvitamin D3 and pentoxifylline (Trental). AB - Human promyelocytic leukemia cell line HL-60 in tissue culture was treated with various concentrations of 1,25-dihydroxyvitamin D3, (D3) pentoxifylline (Px) or in combinations. Differentiation to normal granulocytes or monocytes was evaluated by nitroblue tetrazolium (NBT) reducing capacity and morphologic criteria. (D3) produced monocytic differentiation, but sub-differentiation inducing doses of (Px) had no effect. In previous studies we found higher doses of (Px) to produce granulocytic differentiation in vitro and in vivo. PMID- 8480086 TI - Role of the immune system in recovery from infection. AB - Infection is regarded as an imbalance between microbial pathogenicity factors and the host defense system. The virulence mechanisms include adhesion, chemotaxis, invasion, resistance and production of toxins. In addition, local and/or systemic immune functions in patients undergoing infections are altered. Nonspecific as well as specific cellular and humoral defense mechanisms are affected. The interaction of defined microbial pathogenicity factors with immune effector cells results in the activation of a variety of inflammatory mediators; they are a prerequisite for protective immunity but also induce local or systemic damage in the host when they occur in excessive amounts and when their metabolism is inadequately controlled. The analysis of the pathophysiological events during infection in patients by taking advantage of modern molecular and cell-biological methods may contribute to the development of novel therapeutic strategies. PMID- 8480087 TI - Clinical requirements in the treatment of today's respiratory tract infections. AB - Respiratory tract infections (RTIs) are among the most frequent infections in man and lower tract infections account substantially for the overall mortality in hospitals. Regarding the etiology of pneumonias, one has to consider different pathogenic mechanisms, age of the patients, underlying diseases, concomitant medications, symptomatologies, seasonal influences, and clinical conditions, e.g. intensive care environment and mechanical ventilation. To optimize the rational management of respiratory infections, identification of the etiologic agent would be desirable. The decision of how to treat is often based on epidemiologic, clinical, and radiological assessments. Epidemiologic studies have shown a pronounced difference in the etiologic spectrum between community- and hospital acquired RTIs. In community-acquired pneumonias, pneumococci, Haemophilus influenzae, Legionella, Mycoplasma and viruses predominate, whereas in nosocomially acquired pneumonias, Enterobacteriaceae, e.g. Klebsiella, Proteus, Enterobacter as well as Pseudomonas and staphylococci comprise the most frequent isolates. Empirical therapy has to cover all possible etiologic pathogens which most likely cause the infection. In addition, an adequate kinetic profile, e.g. once or twice daily dosing, sufficient pulmonary tissue or fluid penetration, and acceptable tolerance and costs are prerequisites for optimal therapy. Drugs of choice for the treatment of community-acquired pneumonia are aminobenzylpenicillins or macrolides. Oral cephalosporins exhibit excellent activity against many bacterial pathogens of typical community-acquired pneumonia, and are active against beta-lactamase-producing H. influenzae. PMID- 8480088 TI - Relevance of antibiotic tissue penetration in treating respiratory tract infections. AB - The majority of bacterial respiratory tract infections are caused by streptococci, Haemophilus spp. and Moraxella catarrhalis. These pathogens are located extracellularly. In logical consequence, the bactericidal action of the antimicrobial is required in these loci. To define the reasonable dosing regimen for effective eradication without creating unnecessary toxic potential we need to know (1) the distribution principles and kinetics, and (2) the correct correlation between concentration profiles in extracellular fluid (ECF) and blood. According to the permeability of the vascular capillaries unbound drug concentrations in plasma and ECF are in a dynamic equilibrium. Thus, for the beta lactam antibiotics therapeutic efficacy is predictable by maintaining the free drug concentration above the bacterial minimum inhibitory concentration. Tissue homogenate data can only be useful if correctly interpreted by correcting for the partitioning between the tissue components. PMID- 8480089 TI - Antibiotic treatment of pediatric community-acquired lower respiratory tract infections: challenges and possible solutions. AB - Bacterial pneumonia presents a real challenge in childhood, since its morbidity is impressive, its diagnosis is elusive and the treatment options are not always clear. Despite these difficulties, appropriate management based on an individual approach, good clinical skills and available antibiotics provides a rapid cure to most cases. The problems in diagnosis and treatment as well as the therapeutic approach to childhood bacterial pneumonia are discussed. PMID- 8480090 TI - Literature survey on clinical efficacy and tolerability on cefetamet pivoxil: an analysis of 3,128 cases. AB - The oral third-generation cephalosporin cefetamet pivoxil has a broad spectrum of antibacterial activity and favorable pharmacokinetic properties which makes it particularly suitable for the treatment of upper and lower respiratory tract infections as well as of infections of the urinary tract. The clinical trial results of cefetamet pivoxil have been reviewed from the literature in 4,112 patients out of whom 3,128 patients were treated with cefetamet pivoxil. The standard doses of cefetamet pivoxil, 500 mg twice daily in adults and 10 mg/kg twice daily in children, were at least as effective and in many cases clinically superior to most currently recommended antibiotics for the treatment of complicated urinary tract infections including pyelonephritis. High efficacy has also been demonstrated in patients with pneumonia, in acute exacerbation of chronic bronchitis and infections of the ear, nose and throat. Clinical trial results have shown that a 7-day treatment period with cefetamet pivoxil is as effective as a 10-day course of phenoxymethylpenicillin in the treatment of pharyngotonsillitis due to group A beta-hemolytic streptococci. Cefetamet pivoxil was well tolerated: 226 patients (7.2%) out of 3,128 had adverse events which were mainly gastrointestinal, i.e. diarrhea, nausea and vomiting. An additional 53 (1.7%) patients had laboratory changes which were of no clinical relevance. Premature treatment withdrawals were reported in 13 (0.5%) out of 2,612 adults and in 11 (2.1%) out of 516 children. All adverse events subsided rapidly after treatment. Many current antibiotic treatment regimens require the administration of three daily doses. However, twice daily standard doses of cefetamet pivoxil of 500 mg in adults or 10 mg/kg in children provide unbound plasma concentrations of cefetamet which generally exceed the MIC90 for susceptible organisms between doses and are clinically effective, well tolerated and should result in good compliance. PMID- 8480091 TI - [Clinical features and pathogenesis of Yusho (PCB poisoning)]. AB - The occurrence and progress of Yusho (PCB mass poisoning) is briefly described. Various investigative studies on Yusho are also briefly reviewed. Yusho occurred in the northern district of Kyushu Island in 1968. A specific product of rice oil used for food was accidentally contaminated with PCB during its manufacturing process and consequently, the customers who ate it showed severe intoxication symptoms. Major clinical symptoms of Yusho were acneiform eruptions and circumscribed pigmentation. These skin and mucous membrane eruptions, because of their appearance, caused severe mental suffering for the patients. The government authorized patients amounted to 1,860. These symptoms have gradually declined with the passing of years and presently the principal clinical problems are only various subjective complaints. At first, it was naturally thought that the causative agent of Yusho was PCB (Kanechlor 400) itself. However, it was found later that the causative rice oil contained PCDF (polychlorodibenzofuran) and PCQ (polychloroquaterphenyl) which were proved to be formed during the heating process used in the deodorization of the oil. PCDFs show, in animal studies, a high toxicity and therefore its role for the pathogenesis of Yusho is seriously evaluated in spite of its rather small contaminating amount. On the other hand, PCQs are recognized as the specific marker of Yusho, since almost no PCQ is a general environmental pollution substance. PMID- 8480092 TI - [Neurotoxicity of methyl bromide--neuropathologic evaluation--preliminary study]. AB - Methyl bromide exposure produces disorders of the central and peripheral nervous system. In the literature, there are many neuropathologic studies on the nervous system, especially on the central nervous system, of experimental animals intoxicated with methyl bromide presented. However, in our opinion, a variety of lesions of the nervous system described in the human methyl bromide intoxication have not been well reproduced in the experimental animals. In this study, male Wistar rats were subjected to a 6-hour exposure a day to methyl bromide at a concentration of 500 or 290 ppm 3 days a week for 3 to 8 weeks. The systematic neuropathologic studies of their central and peripheral nervous systems were carried out to reproduce the nervous system lesions in the human methyl bromide intoxication hitherto not produced in the experimental animals. Among the rats exposed to methyl bromide at a concentration of 500 ppm for 10 to 18 days, the axonal degeneration of myelinated fibers at the cervical level of the fasciculus gracilis, which probably corresponds to the degeneration of the spinal posterior column in humans, and the necrosis of the caudate-putamen and atrophy of neurons and pallor of the neuropile in caudate-putamen, thalamus and cingulate cortex, which probably correspond to the degenerative findings of the cerebrum in humans, were found. The rats exposed to methyl bromide at a concentration of 290 ppm for 8 weeks (24 days) did not show any noticeable abnormalities histologically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480093 TI - [Comparison of the casual serum triglyceride levels at health check-up with the values during fasting]. AB - Since higher levels of serum triglycerides were frequently found during the UOEH physical check-up for employees and students in 1989, we analysed subjects with higher triglyceride levels and discussed ways of handling them. Blood sampling to determine serum lipids was done between 13:00-15:00. Of the total (males 1257, females 1267), 272 had higher serum triglyceride levels (over 200 mg/dl) (males 246, females 26) (1st TG). One hundred and twenty-one of the group with higher TG levels in the 1st examination were reevaluated by blood sampling the morning after overnight fasting (2nd TG). There was a significant positive correlationship between the TG levels from the 1st examination and those from the 2nd examination (r = 0.62, n = 121, P < 0.0001). The predictive value calculated from the equation between the TG in the first and second measurements was 341.7 mg/dl. There was a 14.9% rate of false negatives in subjects under 341.7 mg/dl on the first TG measurement. However, there were only 6.3% false negatives in the subjects under 250 mg/dl on the first TG measurement. Age, body mass index and serum cholesterol level were significantly higher in the group with the higher TG level on reevaluation (more than 160 mg/dl) than those in the group with the lower TG level on reevaluation (less than 160 mg/dl). We concluded from these results that the casual serum TG levels above 250 mg/dl might be a suitable cut off level in physical check-ups. PMID- 8480094 TI - [Problems in Papanicolaou classification]. AB - There are several reasons why Papanicolaou classification should not be used for the interpretation of cytologic findings. First, many different classification criteria are sometimes used for a single pathologic condition. Second, inflammatory change or hormonal evaluation are not included in the system. Third, the classification is not compatible for the evaluation of endometrial lesions or chorionic diseases. Fourth, mismanagement of the patient is sometimes encountered when this classification is only used. Instead of Papanicolaou classification, descriptive diagnosis should be used for cytologic interpretation. PMID- 8480096 TI - Developing links to higher education institutions. PMID- 8480095 TI - The ENB framework and higher award. PMID- 8480097 TI - An initiative within higher education. PMID- 8480098 TI - International difficulties. PMID- 8480099 TI - Leading questions. PMID- 8480100 TI - Placing APL on the agenda. PMID- 8480101 TI - Locality-based teaching. PMID- 8480103 TI - Coping with disability. PMID- 8480102 TI - Nurses under stress. PMID- 8480104 TI - Nursing's nature and boundaries. PMID- 8480106 TI - Classroom observation research. PMID- 8480105 TI - Managing educational change. PMID- 8480107 TI - Degrees of change. PMID- 8480108 TI - [Why a "7th Romance Meeting of Immunology and Allergy"?]. PMID- 8480109 TI - [Global approach to the asthmatic patient]. PMID- 8480110 TI - [Indications for intravenous immunoglobulins]. PMID- 8480111 TI - [Targets for immuno-allergic reactions]. PMID- 8480112 TI - [New markers of vasculitis: antineutrophil antibodies]. PMID- 8480113 TI - [Antihistaminics: dangerous medications?]. PMID- 8480114 TI - New vaccines for the world: needs and prospects. PMID- 8480115 TI - [Alcohol and arterial hypertension]. PMID- 8480116 TI - [Duration of rehabilitation and fate of patients with cerebral infarction]. AB - We studied 61 patients with a first stroke, admitted in our rehabilitation center. Functional evolution is usually good, 84% of patients are able to return at home, after a mean of 4.6 months of rehabilitation. Age, sex, severity of the initial deficit, shoulder-hand syndrome, etiology and localisation of stroke are the factors which determine the functional recovery and duration of hospitalisation. PMID- 8480117 TI - [Growth and hormones: from fetus to adult]. PMID- 8480118 TI - [From hypercalcemia to the discovery of a new hormone: PTHrP]. PMID- 8480119 TI - [Headache and acute respiratory distress in a young woman]. PMID- 8480120 TI - [Treatment of hospital and medical waste in the Canton of Vaud: why, by whom and how?]. PMID- 8480121 TI - [Consensus: cum sensu?]. PMID- 8480122 TI - [Faradization according to Duchenne de Boulogne (1855)]. PMID- 8480123 TI - [Concerning Heraieff's article ob obesity in the Revue medicale de la Suisse Romande (No.11, Vol.112, November 1992)]. PMID- 8480124 TI - Hospital won't limit duties of HIV+ pharmacist. PMID- 8480125 TI - Public perceptions about AIDS are at odds with facts. PMID- 8480126 TI - To flush or not to flush with heparin. PMID- 8480127 TI - Fractures are never simple. PMID- 8480128 TI - Now I stand up for my patients. PMID- 8480129 TI - OTC interactions. Asthma medications. PMID- 8480130 TI - A nurse's guide to implanted ports. PMID- 8480131 TI - Patient teaching for x-ray and other diagnostics. Transesophageal echocardiogram. PMID- 8480133 TI - Fat substitutes--a closer look. PMID- 8480132 TI - Assessing pediatric rashes. PMID- 8480134 TI - Sorbitol isn't always a sweet deal. PMID- 8480135 TI - Statistics don't always tell the whole story. PMID- 8480136 TI - When a merger involves opposing religious doctrines. PMID- 8480137 TI - Less isn't more if you can't read it. PMID- 8480138 TI - Association of HLA class I and class II antigens with rheumatic fever in a Turkish population. AB - The distribution of class I and class II HLA antigens of 100 Turkish patients with rheumatic fever, 77 of whom had cardiac involvement, was examined. We compared the results with a control group of identical origin. The frequency of HLA A10 and HLA B35 antigens were found significantly higher in patients with rheumatic fever (p < 0.05, p < 0.01, respectively). The frequency of HLA A10 and HLA DRw11 in patients with cardiac involvement were significantly higher than in those without cardiac involvement (p < 0.05, p < 0.01, respectively). On the other hand, HLA Cw2 antigen frequency was found significantly higher in patients without cardiac involvement than in those with rheumatic heart disease (p < 0.05). We support the concept that rheumatic fever is an immunological reaction to group A, beta hemolytic streptococci in individuals who have genetic predisposition. PMID- 8480139 TI - Evaluation of criteria contributions for the classification of systemic lupus erythematosus. AB - The American Rheumatism Association (ACR) preliminary and revised criteria for classification of systemic lupus erythematosus (SLE) were evaluated for sensitivity and specificity in a population of 100 patients with SLE and 100 patients with other rheumatic diseases. Bayes' theorem was applied for evaluation of ARA criteria for the classification of SLE and a scoring system was developed which allows simple determination of the probability of SLE. The evaluation revealed considerable differences in values of the ARA criteria. The serologic tests and discoid lupus appeared to be the most distinctive criteria, while Raynaud's phenomenon, oral and nasal ulcers and arthritis were of little value. Comparison of SLE and control patients presenting the same number of criteria revealed that patients with SLE exhibit more distinctive criteria. This finding emphasizes the need for a quantitative evaluation of classification criteria. PMID- 8480140 TI - More evidence of distinctive features of mixed connective tissue disease. AB - A comparison of clinical, immunological and HLA-D region antigen features was made between 22 patients with mixed connective tissue disease (MCTD) and 118 patients with systemic lupus erythematosus (SLE), scleroderma or primary Sjogren's syndrome. The MCTD patients had hypergammaglobulinemia more often than did those with SLE and scleroderma, but had less skin ulceration, serositis, nephritis, central nervous system disease and hypocomplementemia than the SLE patients. The frequencies of HLA-DR4 and its Dw4 subtype were significantly increased in MCTD as compared with both the other patient groups and healthy controls. Anti-RNP antibodies and the clinical characteristics together seem to illustrate a disease syndrome which is clinically and genetically distinct and fits with the prevailing concept of MCTD. PMID- 8480141 TI - Clinical features in patients with chronic muscle pain--with special reference to fibromyalgia. AB - Clinical characteristics were studied in patients with chronic muscle pain, divided into three groups according to the characteristics of their pain; "fibromyalgia" (n = 23), "widespread muscle pain" (n = 21), and "regional muscle pain" (n = 28). Typical fibromyalgia features were also seen in the other groups of patients, but not to the same extent. In particular, sleep disturbance, subjective swelling, cold and exercise intolerance and low self-reported physical performance were significantly related to fibromyalgia. The major components of fibromyalgia were not wholly different compared with other European and North American studies, except for sleep disturbance and subjective swelling, which was somewhat more pronounced in this study. The most used medications in fibromyalgia patients at referral were analgesics, anxiolytic drugs and female sex hormones. Medication in fibromyalgia was not excessive and seemed appropriate compared to the other patient groups. Effects of various biases and classification criteria on the results of fibromyalgia studies are discussed. The characteristic features of fibromyalgia, its stability when diagnosed and the promotion of research and patient management justify the current classification of fibromyalgia at this stage. PMID- 8480142 TI - Proresid therapy in rheumatoid arthritis. A comparison with injectable gold using life-table analysis. AB - Proresid, mainly consisting of podophyllotoxin derivatives and two glycosides thereof, has been used as a disease-modifying antirheumatic drug in Sweden since the late 1960s. A life-table analysis of Proresid treatment averaging 41 months (range 4-144) in 79 rheumatoid arthritis patients showed a termination rate of 40, 56, 75 and 85% after 1/2, 1, 2 and 4 years, respectively. Dominant reasons for discontinuing therapy were inefficacy (37%) and gastrointestinal symptoms (35%). The risk of discontinuation of therapy due to inefficacy was constant over time, while the risk due to other causes, including side effects, gradually decreased. A comparison with injectable gold therapy showed, after adjusting for confounding factors, that the total termination incidence was higher (p < 0.05) in the Proresid-treated patients. A comparison with the regional cancer register of 334 patients exposed to Proresid for a mean time of 2.2 years showed no increased cancer risk after a mean observation time of 6.1 years. PMID- 8480143 TI - Cyclosporin treatment in rheumatoid arthritis is associated with an increased serum activity of beta-glucuronidase. AB - The serum activity of beta-glucuronidase (beta-gluc) has been presumed to indicate the disease activity in rheumatoid arthritis (RA). In 10 patients with RA the serum beta-gluc was repeatedly determined after the initiation of a treatment with cyclosporin for one year. A significant increase of beta-gluc was found after 8, 12 and 16 weeks compared to the values before treatment, while the concentration of the soluble interleukin 2-receptor decreased. The data reveal, that beta-gluc is not a useful indicator of the disease activity during cyclosporin treatment. PMID- 8480144 TI - The course of erythropoietin in patients with rheumatoid arthritis with normal and low blood-hemoglobin. A longitudinal study. AB - A consistent elevated level of erythropoietin was found in eight patients with R.A., who continuously for 10 years had a low hemoglobin (< 8 mmol/l) compared with nine patients with R.A., who had a normal hemoglobin (> or = 8 mmol/l) (p = 0.017). A significant inverse correlation between erythropoietin and hemoglobin (r = -0.61) was found in the low-hemoglobin group, but not in the normal hemoglobin group. Erythropoietin was not found to be correlated to clinical variables. PMID- 8480145 TI - Pulmonary pseudolymphoma presented with a mass lesion in a patient with primary Sjogren's syndrome: beneficial effect of intermittent intravenous cyclophosphamide. AB - A 61-year-old woman with primary Sjogren's syndrome (SS) presented with fever, dry cough, dyspnea on exertion, and a mass lesion with reticular shadowing at both bases on her chest X-ray. Pulmonary pseudolymphoma was diagnosed by transbronchial lung biopsy which revealed infiltration of T cell-like slightly atypical lymphoid cells. After three infusions of cyclophosphamide (750 mg every 4 weeks) combined with prednisolone, the pulmonary mass lesion was diminished and her symptoms improved. Evaluation of the 12 reported cases of pulmonary pseudolymphoma with SS that presented with mass lesions showed an increase in IgM level, frequent pulmonary fibrosis, precedence of SS, and better prognosis with immunosuppressants in those patients. PMID- 8480146 TI - Adult idiopathic polymyositis without elevation of creatine kinase. Case report and review of the literature. AB - A patient fulfilling diagnostic criteria for definite polymyositis, but with normal levels of creatine kinase (CK) is reported. Review of the literature reveals significant variations regarding the frequencies of normal CK reported among cases with myositis. The discrepancies may be partly explained by inclusion of both probable and possible polymyositis, administration of steroid therapy prior to estimations of CK, and possible differences in CK levels between polymyositis and dermatomyositis. The patient reported did not suffer from neither lung disease nor concomitant malignancy. Thus, the alleged association between low levels of CK and poor prognosis in myositis could not be supported by the present case report. PMID- 8480147 TI - [The DHS (dynamic hip screw) buttress plate in the management of unstable proximal femoral fractures]. AB - The DHS-implant system is a technically simple and widely used operative treatment modality for pertrochanteric fractures of the femur. In unstable 4-part fractures rotation of the head and neck fragment around the lag screw and significant impaction might lead to lateralisation of the greater trochanter and therefore to marked shortening. To prevent these effects we treated 17 patients with 4-part fractures with a prototype of a modular trochanteric DHS buttress plate. With this additional implant lateralisation of the greater trochanter could be prevented in all cases. This also leads to a limitation of telescoping, with less shortening even with immediate full weight bearing. PMID- 8480148 TI - [Laparoscopic cholecystectomy in a teaching center. Apropos of 208 interventions]. AB - Laparoscopic cholecystectomy is a relatively recent acquisition and still remains limited to a few surgeons. We started an education program for surgeons used to open biliary surgery. Between September 1990 and December 1991, 208 patients have been operated on day 14 operators flanked by 2 teachers. Technique was standardized and all patients were examined preoperatively for absence of stones in bile ducts using i.v. cholangiography and tomography. Only 6 patients (< 3%) needed to be converted to laparotomy. Morbidity was less than 6% and due to minor complications. Only one patient needed reoperation because of incisional hernia. Mortality was nil. Mean postoperative hospitalization time was less than 3 days. We conclude that laparoscopic activity in a teaching center allows acquisition of a new technique modality while remaining safe for patients. PMID- 8480149 TI - [Multiple tumors of colon and rectum]. AB - The possible occurrence of multiple synchronous or metachronous malignant lesions in patients with carcinoma of the colon and rectum is a well known event. In this population-based study in the Geneva area from 1970 to 1986, the frequency of synchronous colorectal carcinomas was 1.1% and that of metachronous carcinomas 1%. The relative risk of metachronous colorectal carcinoma is higher than in the general population (colon after rectum 1.2, colon after colon 1.7 and rectum after rectum 1.4). A high association of adenomatous polyps with multiple colorectal carcinoma was observed. The 5-year actuarial survival in case of curative resection was 87% for metachronous carcinomas, 35% for single carcinomas and 33% for synchronous carcinomas. We conclude that complete preoperative colonoscopy, whenever possible, should be performed to screen patients with synchronous carcinomas. Finally, a lifelong follow-up of the residual colon or rectum should be planned to detect metachronous lesions. PMID- 8480150 TI - [Multiple organ removal from the viewpoint of the non-transplanting hospital. Cost, yield, problems]. AB - Our algorithm is an example of the way in which multiple organ donation can be organized in a hospital which does not perform transplants. We describe problems which arise during evaluation of the donor and pending explanation. In conclusion we call for better coordination and support from transplantation centres. PMID- 8480151 TI - [The significance of computerized tomography in the conservative treatment of liver injuries]. AB - Increasing experience with early radiological evaluation by ultrasound (US) and computed tomography (CT) of patients with abdominal trauma is leading to more frequent use of conservative treatment in patients with severe liver injuries. In a retrospective study with predominant use of peritoneal lavage only 3 out of 100 patients with liver injuries were treated non-surgically. In a consecutive prospectively evaluated series of 75 patients with early use of US and CT, 30 patients in stable circulatory conditions were treated non-surgically. With increasing experience a higher percentage of patients, even with severe liver injuries, could be treated non-operatively. 17 patients with minor injuries (grade I and II, modified according to Moore) and 13 patients with severe injuries (grade III and IV) could be treated non-surgically. 2 patients with grade IV injury developed an arterial/portal-venous fistula and an arterial aneurysm which necessitated radiological embolizations. All conservatively treated patients have been followed up for a mean period of 18 months without complications. Although a precise anatomical classification of the liver injury degree seems difficult, the predictive value of computed tomography for non surgical treatment was good. Use of i.v.-contrast is mandatory. We conclude that in experienced hands computed tomography allows precise evaluation of liver injuries for adequate treatment, provided careful follow-up (intensive care unit, CT, angiography) ensues to avoid complications. PMID- 8480152 TI - [Unstable spinal injuries in cranio-cerebral injuries]. AB - Estimates of the incidence of injury to the cervical spine among patients suffering blunt trauma to the head vary widely. In an attempt to quantify the risk, the records of 593 consecutive patients with blunt craniocerebral injuries admitted to our trauma center in 1991 were reviewed. The overall incidence of cervical spine injuries was 5.8% and for unstable cervical spine injuries 2.9%. In the management of head trauma with associated cervical spine injuries realignment and immobilization of the spine and surgery of the head were carried out as first step, followed by decompression and stabilization of the affected segment in the same session. In patients with altered consciousness there is always loss of cooperation and early spinal stabilization for optimal treatment in the intensive care unit and in the wake-up-phase is important. PMID- 8480153 TI - [Initial results with the unreamed AO tibial nail]. AB - It is generally accepted that intramedullary nailing in combination with reaming should be avoided in treating open fractures. However, the use of an unreamed, solid nail combined with interlocking also allows stabilization of open and complex fractures. 20 tibia fractures (65% open, 45% complex fractures) have been treated by the AO unreamed tibial nail (UTN), 12 (5 of them open fractures) by direct nailing and 8 after initial stabilization by an external fixator. In our series no intraoperative complications, no soft-tissue healing problems and no infections occurred. Thus, treatment of both open and comminuted fractures by UTN appears to be safe and generally needs no secondary stabilization. PMID- 8480154 TI - [Preoperative arthroscopy in fresh complicated internal knee lesions]. AB - In a prospective study, 197 preoperative arthroscopies were carried out on 194 patients with fresh severe internal lesions of the knee. The injuries are analyzed, with reference in particular to diagnosis and treatment of additional meniscus lesions. Advantages and disadvantages of the procedure are discussed. PMID- 8480155 TI - [Incidence of ileus following rectum resection in rectal carcinoma with or without radiotherapy]. AB - Between 1984 and 1989 240 patients underwent radical abdominal resection of a rectal carcinoma. Out of 201 patients surviving 12 months or more postoperatively, two groups are surveyed. The first group presents patients undergoing adjunctive radiation therapy (n = 47), while the second group did not undergo postoperative radiation therapy (n = 134). Mean follow-up time postoperatively is 39 months. Within the irradiation group, the incidence of ileus was found to be 23% (11/47), and in the non-irradiated group 8% (11/134). Subsequent reoperations in order to clear intestinal obstruction were performed on 4% (5/134) of non-irradiated patients and on 21% (10/47) of the irradiated group. Considering the increased risk of postoperative ileus after rectal resection for rectal carcinoma, serious reflection should be given to assessing the appropriateness of adjunctive radiation therapy. PMID- 8480156 TI - [Digestive system carcinoid tumor and synchronous malignant tumors]. AB - 270 digestive carcinoid tumors have been diagnosed at the Pathology Institute of Lausanne between 1971 and 1990; of these 21 were associated with other, synchronous, tumors: 7 of the carcinoids were from the appendix (33%), 8 from the small bowel (38%), 4 were from the colorectum (25%), one from the duodenum (4.5%) and finally one from the stomach (4.5%). Two thirds (14) were associated with adenocarcinomas of the colon, the rest with 2 gastric tumors, 1 tumor of the appendix, 1 of the gallbladder, 1 of the small gut, 1 of the duodenum and 1 of the peritoneum. The mean age of the patients was 70 years, which correlates with the large proportion of carcinomas of the colon. The males (16) clearly outnumbered the females (5) for no obvious reason. 80% of the carcinoids were discovered during the treatment of the associated tumor. Survival was directly related to the stage and aggressivity of the malignant tumor. The carcinoid itself hardly changed the prognosis, except for one case of liver failure due to metastases from carcinoid of the stomach associated with an adenocarcinoma. The histologic features of the carcinoid tumors were unexceptional. Different hypotheses to explain the associations are formulated. PMID- 8480157 TI - [Hemodynamic effects of the implantation of an intracaval oxygenator]. AB - Treatment of severe respiratory failure by extracorporeal membrane oxygenation (ECMO) is complex. However, there is now an intravascular gas exchanger (IVOX) available that provides extrapulmonary gas transfer without requiring an extracorporeal blood path. The present study was performed to determine the hemodynamic effects resulting from the intracaval placement of the intravascular device. A bovine model (n = 6; body-weight = 72 +/- 5 kg) was selected for temporary lung support with the intravascular device. The latter was placed in the caval axis under fluoroscopic control after full instrumentation of the animal for hemodynamic measurements including a pulmonary artery catheter for determination of cardiac output by thermodilution and continuous readout of mixed venous oxygen saturation. All measurements were taken after a stabilization period of 15 min. The heart rate moved from 65 +/- 8 before to 72 +/- 10 after implantation and 68 +/- 9 after onset of intravascular gas exchange (NS). Right atrial pressure was 13 +/- 3 mm Hg before, 12 +/- 3 mm Hg after implantation and 10 +/- 3 mm Hg after onset (NS) whereas femoral venous pressure moved from 14 +/- 3 mm Hg to 17 +/- 4 mm Hg (p < 0.05) and remained at 17 +/- 4 mm Hg after onset. Cardiac output was 5.3 +/- 0.7 l/min before, 5.4 +/- 0.7 l/min after implantation and 5.3 +/- 1.1 l/min after onset (NS) while mixed venous oxygen saturation dropped from 60 +/- 7% to 54 +/- 11% and moved to 57 +/- 11 after onset of the device (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480158 TI - [Islet of Langerhans transplantation in humans]. AB - Islet of Langerhans transplantation is an alternative to whole pancreas transplantation for type I diabetic patients, in whom exogenous insulin therapy has not prevented the occurrence of systemic complications. Thanks to a new isolation technique of human islets, 45 patients have been transplanted worldwide since 1988, of whom only 7 have become totally insulin-independent. Rejection and quality of the islet preparations are problems which remain to be solved. Autotransplantation of islets has been proposed in patients undergoing a pancreatectomy for benign disease. The present report concerns two of our patients who had a pancreatectomy with islet autotransplantation. Both patients are insulin-independent 3 and 11 months postoperatively, with satisfactory metabolic tests. Islet autotransplantation can be proposed when pancreatectomy for non-malignant disease is performed. This method may prevent the development of insulin-dependent diabetes, known to be particularly labile. Because of the sophisticated technical procedures required, human islet isolation is at present only performed in a small number of medical centers and still is in the field of medical experimentation. PMID- 8480159 TI - [Platelet aggregation inhibitor and brain infarct: quo vadis?]. PMID- 8480160 TI - [Whiplash injury--a confusing concept]. AB - The functional anatomy of the cervical spine, the biomechanics of lesions due to rear end collisions, the human behaviour of victims of these collisions and the influence of insurance, legislation, court decisions and the modalities and duration of treatment are discussed in a survey of the literature on lesions of the cervical spine due to rear end collisions. The problems posed by changed court rulings on lesions of the cervical spine due to rear end collisions are mentioned, as well as the danger of producing a "whiplash" compensation epidemic. It appears that immediate treatment of the lesion avoiding manipulation, long immobilization and delay in decisions on compensation may reduce the frequency, intensity and duration of symptoms. The symptoms usually remit after settlement of compensation and seldom give rise to substantial disability. The prevention of lesions of the cervical spine and head due to rear end collisions will only be possible if car safety engineers succeed in preventing rear end collisions and/or in ending hyperextension by appropriate devices. The head supports in use today are not sufficient to prevent hyperextension of the cervical spine. PMID- 8480161 TI - [Is extracorporeal cholelithotripsy still justified as treatment in cholelithiasis?]. AB - This prospective study evaluates the results of extracorporeal shock-wave piezoelectric lithotripsy in 52 patients, 41 with radiolucent and 11 with calcified shell gallstones. The fragmentation rate was above 90% and the complication rate 31%, with pain or intolerance to the adjuvant dissolution therapy in particular. At the end of the treatment, 7 cholecystectomies were carried out among the 31 patients in whom lithotripsy failed. After 18 months, the success rate was 23% and only 12 patients remained stone free. Nowadays, thanks to the new laparoscopic therapy, extracorporeal shock-wave lithotripsy is no longer judged appropriate, particularly in view of its poor cost-effectiveness and high recurrence ratio. PMID- 8480162 TI - [Extracorporeal shockwave lithotripsy of the gallbladder: importance of selection criteria]. AB - In recent years, a number of alternatives to surgery for gallstones have been developed. Among them, extracorporeal shock-wave lithotripsy (ESWL) was promising, being non-invasive and risk-free. Nevertheless, its results vary according to the size, number and composition of the stones and according to the bile acids treatment used for fragment dissolution. To better evaluate the importance of these factors, we have widened the selection criteria currently used (1 to 3 non-calcified stones with a diameter below 30 mm) by including patients with large stones (up to 40 mm in diameter), multiple stones (up to 10 stones) and calcified stones. We also compared, for efficacy of fragment dissolution after ESWL, treatment by ursodeoxycholic acid alone as opposed to a mixture with chenodeoxycholic acid. Our results were (1) significant lessening of the fragmentation rate and of the number of gallbladders free of stones 1 year after ESWL when selection criteria are widened; (2) a mixture of ursodeoxycholic and chenodeoxycholic acids may favour fragment dissolution after ESWL compared to treatment by ursodeoxycholic acid alone. PMID- 8480163 TI - [Diffuse idiopathic skeletal hyperostosis (DISH) and pseudo-coxarthritis following long-term etretinate therapy]. AB - A 51-year old patient with congenital basal cell naevus syndrome was treated with etretinate (50-100 mg/daily) over a period of 5 years (cumulative dose 110 g). Clinically he developed a stiff back with pronounced disability of both hips. Radiologically, axial involvement of the spine with severe diffuse idiopathic skeletal hyperostosis especially of the lumbar spine, and ossifications of both hips were documented. Rheumatological implications of long-term therapy with etretinate are discussed. PMID- 8480164 TI - [Neurological side effects following vaccination of early-summer meningoencephalitis. Case report and experiences of the Swiss Center for Adverse Drug Effects]. AB - Two weeks after vaccination against tick-born encephalitis (TBE) a 69-year-old patient developed subacute myelo-polyradiculitis. The neurological symptoms subsided after a few weeks. Alerted by this observation, we scanned the database of the Swiss Drug Monitoring Center (SANZ) for similar case reports. Of twenty spontaneous reports 11 concerned neurological side effects closely related to TBE vaccination. We conclude that TBE vaccination is associated with substantial neurological side effects and should, therefore, remain restricted to individuals at high risk for TBE. PMID- 8480165 TI - [Concerning: "Long-term course in differentiated thyroid carcinoma" by H. Rosler, A. Birrer, D. Luscher and J. Kinser (Schweiz. med. Wschr. 1992; 122: 1843-1857)]. PMID- 8480166 TI - The economics of life and death. AB - Mortality data can be used to analyze economic performance. Such information can illuminate critical aspects of the economic organization of society. PMID- 8480167 TI - Moderation in science budgeting. PMID- 8480168 TI - Database contamination. PMID- 8480169 TI - Database contamination. PMID- 8480170 TI - Sequencing the human genome. PMID- 8480171 TI - Congress may hang up on AIDS hotline. PMID- 8480172 TI - Sex surveys come out of the closet. PMID- 8480173 TI - Genetic 'master switch' for left-right symmetry found. PMID- 8480174 TI - Cytokines and estrogen in bone: anti-osteoporotic effects. PMID- 8480175 TI - Imaging of features on surfaces by condensation figures. AB - Condensation of a vapor to a liquid on a cold surface that is not wet completely by this liquid leads to the formation of an array of droplets. If the surface is heterogeneous in its physical properties (especially its interfacial free energy), the patterns of these arrays reflect this heterogeneity. The distribution of droplets of water (condensation figures or CFs) observed by optical microscopy on a surface can be correlated with the molecular structure of that surface. The substrates used to investigate the formation and morphology of the CFs were patterned, self-assembled monolayers of different alkanethiolates on gold and of alkyl siloxanes on glass. Analysis of CFs is a valuable nondestructive technique for characterizing heterogeneities in surfaces. PMID- 8480176 TI - Social structure of pilot whales revealed by analytical DNA profiling. AB - Long-finned pilot whales swim in large, extremely cohesive social groups known as pods. Molecular typing revealed that pod members form a single extended family. Mature males neither disperse from nor mate within their natal pods, a situation unusual for mammals. Such behavior could be explained in terms of inclusive fitness benefits gained by adult males helping the large number of female relatives with which they swim. PMID- 8480177 TI - Where plants make oxygen: a structural model for the photosynthetic oxygen evolving manganese cluster. AB - In the photosynthetic evolution of oxygen, water oxidation occurs at a catalytic site that includes four manganese atoms together with the essential cofactors, the calcium and chlorine ions. A structural model and a determination of the manganese oxidation states based on x-ray absorption spectroscopy are presented. The salient features, in both higher plants and cyanobacteria, are a pair of di mu-oxo bridged manganese binuclear clusters linked by a mono-mu-oxo bridge, one proximal calcium atom, and one halide. In dark-adapted samples, manganese occurs in oxidation states (III) and (IV). Data from oriented membranes display distinct dichroism, precluding highly symmetrical structures for the manganese complex. PMID- 8480178 TI - Reversal of left-right asymmetry: a situs inversus mutation. AB - A recessive mutation was identified in a family of transgenic mice that resulted in a reversal of left-right polarity (situs inversus) in 100 percent of the homozygous transgenic mice tested. Sequences that flanked the transgenic integration site were cloned and mapped to mouse chromosome 4, between the Tsha and Hxb loci. During early embryonic development, the direction of postimplantation turning, one of the earliest manifestations of left-right asymmetry, was reversed in homozygous transgenic embryos. This insertional mutation identifies a gene that controls embryonic turning and visceral left right polarity. PMID- 8480179 TI - Intermediate filament formation by a yeast protein essential for organelle inheritance. AB - Intermediate filaments are abundant cytoskeletal components whose specific cellular functions are poorly understood. The Saccharomyces cerevisiae protein MDM1 displays structure and solubility properties that are similar to those of intermediate filament proteins of animal cells. Yeast cells that have a mutant form of MDM1 exhibit temperature-sensitive growth and defective transfer of nuclei and mitochondria to daughter cells during incubation at the nonpermissive temperature of 37 degrees C. The purified, wild-type MDM1 protein readily forms 10-nanometer-wide filaments at either 4 degrees C or 37 degrees C. In contrast, the purified, mutant protein forms filaments at 4 degrees C but fails to form such structures at 37 degrees C. These results suggest that intermediate filament proteins are universal components of eukaryotic cells. PMID- 8480180 TI - Retinoic acid stimulates regeneration of mammalian auditory hair cells. AB - Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage. PMID- 8480181 TI - Linkage on chromosome 3 of autoimmune diabetes and defective Fc receptor for IgG in NOD mice. AB - A congenic, non-obese diabetic (NOD) mouse strain that contains a segment of chromosome 3 from the diabetes-resistant mouse strain B6.PL-Thy-1a was less susceptible to diabetes than NOD mice. A fully penetrant immunological defect also mapped to this segment, which encodes the high-affinity Fc receptor for immunoglobulin G (IgG), Fc gamma RI. The NOD Fcgr1 allele, which results in a deletion of the cytoplasmic tail, caused a 73 percent reduction in the turnover of cell surface receptor-antibody complexes. The development of congenic strains and the characterization of Mendelian traits that are specific to the disease phenotype demonstrate the feasibility of dissecting the pathophysiology of complex, non-Mendelian diseases. PMID- 8480182 TI - Immuno-PCR with a commercially available avidin system. PMID- 8480183 TI - Lung cancer. Part 1. Introduction. PMID- 8480184 TI - The biology of lung cancer. PMID- 8480185 TI - Chemoprevention of lung cancer. PMID- 8480186 TI - Imaging in lung cancer. PMID- 8480187 TI - Human erythrocyte membrane protein band 4.2 (pallidin). PMID- 8480188 TI - Molecular genetics of the glycophorin A gene cluster. PMID- 8480189 TI - Glycophorin C and related glycoproteins: structure, function, and regulation. PMID- 8480190 TI - Ankyrins: structure and function in normal cells and hereditary spherocytes. PMID- 8480191 TI - The challenges of inhibitor patient care. PMID- 8480192 TI - Use of porcine factor VIII for surgical procedures in hemophilia A patients with inhibitors. AB - We have described the use of polyelectrolyte fractionated porcine factor VIII (HYATE:C, Porton Speywood Ltd, Wrexham, UK) to provide hemostasis in 45 patients with hemophilia A complicated by inhibitor antibodies. The cases were collected from hemophilia care providers in seven nations and represent some of the experience with porcine factor VIII generated over the past 12 years. A wide variety of procedures was performed with varying degrees of associated hemostatic challenge in a difficult treatment group. The patients were representative of the hemophilia population in general and ranged in age from 1 to 67 years. The results of our survey should encourage clinicians to consider use of porcine factor VIII to provide hemostatic coverage in hemophilia patients with inhibitors who require surgical procedures. Hemostatic coverage was satisfactory in the vast majority of episodes; there have been only a small number of easily controlled, well-tolerated adverse reactions, which were usually self-limited in nature. No life-threatening reactions to porcine factor VIII were seen during coverage for surgical procedures in our survey, although serious reactions can occur as noted above. This is remarkable, since surgical patients usually are treated with higher doses of porcine factor VIII for greater periods of time than most other hemophilic patients treated for hemarthroses or soft-tissue bleeding, for example. Thrombocytopenia in association with porcine factor VIII therapy has been a major concern since the first crude preparations were used in the 1950s. Modern series, however, note the incidence of thrombocytopenia in only a minority of patients treated with the current polyelectrolyte fractionated preparations of porcine factor VIII. In our series, thrombocytopenia with platelet counts of less than 150 x 10(9)/L occurred in 11 of 54 treatment episodes (20%). The mechanism for thrombocytopenia demonstrated in a previous study involves porcine von Willebrand factor, which may copurify with porcine factor VIII and cause platelet aggregation and/or clearance from the circulation. The phenomenon of thrombocytopenia appears to be related to the administration of high doses of porcine factor VIII in some cases; however, in other patients, it may develop inconsistently at modest doses. It may be that there are idiosyncratic differences between patients that determine the dose of porcine factor VIII likely to cause thrombocytopenia. As yet, there is no way to predict which patient will develop thrombocytopenia while being treated with porcine factor VIII.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8480193 TI - The treatment of acquired factor VIII inhibitors: worldwide experience with porcine factor VIII concentrate. International Acquired Hemophilia Study Group. PMID- 8480194 TI - Immunosuppression of factor VIII inhibitors in nonhemophilic patients. PMID- 8480195 TI - Diagnosis of factor VIII versus nonspecific inhibitors. PMID- 8480196 TI - Continuous infusion of porcine factor VIII for the treatment of patients with factor VIII inhibitors. PMID- 8480197 TI - Prediction and management of adverse events associated with the use of factor IX complex concentrates. AB - Among the adverse events that have been associated with the use of F IX CC in inhibitor patients, the likelihood of transmission of blood-borne pathogens is now greatly reduced. However, one must be aware of the possibility of thrombotic complications and acute myocardial infarction when using large, repetitive doses of F IX CC. A greater awareness of such potentially life-threatening complications, and avoidance of frequent, repetitive large doses, should decrease the risk. F IX CC are not always effective in achieving or maintaining hemostasis in hemophiliacs with inhibitors. Thus, in subjects who are responding suboptimally, in those in need of surgical intervention, or in those who have large intramuscular hemorrhages and/or will require a prolonged period of treatment, alternative therapeutic approaches should be considered. PMID- 8480198 TI - World registry on factor VIII inhibitor patients: why? PMID- 8480199 TI - Radiographic features that enable assessment of first metatarsal rotation: the role of pronation in hallux valgus. AB - This study describes a method of detecting first metatarsal pronation on the basis of the movement of the inferior tuberosity of the base of 20 cadaveric first metatarsals at 0 degrees, 10 degrees, 20 degrees and 30 degrees pronation. On pronation, the inferior tuberosity of the base of the first metatarsal moved lateral to the mid-line axis. At 10 degrees, the tuberosity pointed to the junction of the inner third and outer two-thirds of a line between the midpoint and lateral tubercle of the base. At 20 degrees, it pointed to the junction of the inner two-thirds and outer third of that line. At 30 degrees, it pointed to the outer margin of the lateral third. Using these features, the amount of first metatarsal pronation in 100 consecutive weight-bearing views of feet was recorded and plotted against the corresponding intermetatarsal angles in those feet. Four of 43 patients with an intermetatarsal angle of less than 9 degrees had pronation greater than 10 degrees, 48 of 57 patients with an intermetatarsal angle greater than 9 degrees had pronation greater than 10 degrees (P < 0.001). As intermetatarsal angles increase, the amount of first metatarsal pronation increases (r = 0.69). Pronation and varus deviation of the first metatarsal are linked; both alter the tendon balance maintaining proximal phalanx alignment and lead to the development of hallux valgus. PMID- 8480200 TI - Eosinophilic granuloma: MRI manifestations. AB - The appearance on magnetic resonance imaging (MRI) of 16 cases of pathologically proven eosinophilic granuloma were reviewed retrospectively and correlated with the radiographic appearance of the lesion. The most common MR appearance (ten cases) was a focal lesion, surrounded by an extensive, ill-defined bone marrow and soft tissue reaction with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, considered to represent bone marrow and soft tissue edema (the flare phenomenon). The MRI manifestations of eosinophilic granuloma, especially during the early stages, are nonspecific, and may stimulate an aggressive lesion such as osteomyelitis or Ewings sarcoma, or other benign bone tumors such as osteoid osteoma or chondroblastoma. PMID- 8480201 TI - MR imaging of eosinophilic granuloma: report of 11 cases. AB - The findings in 11 patients with histologically proven eosinophilic granuloma (EG) examined by magnetic resonance imaging (MRI) are described. In contrast with the variable appearance of EG on conventional radiography and computed tomography (CT), relatively constant features--intermediate to high signal intensity on T1 weighting, high signal intensity on T2-weighting, marked enhancement--were found on MRI. MRI was superior to other imaging methods in demonstrating bone marrow involvement and any accompanying soft tissue mass or inflammation. Intermediate to high signal intensity on T1-weighting and marked contrast enhancement could not be "explained" by histological findings. Prediction of the evolutionary phase of EG by MRI remains questionable because of the phase I (proliferative) histology of all 11 lesions. PMID- 8480202 TI - Factors affecting the thickness of the cervical prevertebral soft tissues. AB - Lateral cervical spine films of 227 patients examined over 2 years were analyzed to determine the thickness of the soft tissues anterior to C2 through C4. These measurements were correlated with patient age, sex, weight, shoulder width, neck width, and calculated radiographic magnification. We found that only patient weight and age had any statistically significant effect on the soft tissue thickness. A stepwise regression model produced a simple equation for predicting the mean value of the soft tissue thickness (specifically at C3) using the patient's age and weight: C3 width = 3.7 mm-0.02 x age (years) + 0.01 x weight (pounds). Using this formula we determined that weight and age account for 28% of the observed variability in the soft tissue measurements at C3. These relationships were similar at C2 and C4. Interestingly, patient sex and radiographic magnification had no detectable effect on the measured widths. PMID- 8480203 TI - Giant cell tumor in children and adolescents. AB - The radiological appearance of giant cell tumors (GCT) in the developing skeleton was retrospectively assessed in 49 (10.6%) of the 462 patients with GCTs seen in consultation by the Netherlands Committee on Bone Tumors. There were 31 female and 18 male patients, all below 19 years of age. Thirty-four tumors were located in short and long tubular bones, two in the tarsus, while the others were in the pelvis, vertebral spine, and a rib. Involvement of the epiphysis in tubular bones was closely related to the age of the patient: the average age of the 3 patients with a lesion in the metaphysis was 11 years, that in the 6 patients with metadiaphyseal lesions 13 years, average age in the 10 patients with epimetaphyseal lesions 17 years, and it was also 17 years in the 17 patients with epimetadiaphyseal lesions. In tubular bones with the epiphyseal growth plates still open, the epiphysis was never involved, with the exception of two epimetadiaphyseal lesions in which closure of the growth plate was difficult to establish. Assessing GCT characteristics in this study population demonstrated that epiphyseal involvement increased with age and showed; to some extent, a predominance of female patients. PMID- 8480204 TI - Radiographic assessment of sagittal knee instability in weight bearing. A study on anterior cruciate-deficient knees. AB - In 16 patients with chronic, symptomatic anterior cruciate ligament-deficient knees, sagittal displacement was studied in the standing position using fluoroscopic control and a simple device to support the knee. In slight weight bearing all knees but one had normal femorotibial alignment in the lateral view. During full weight bearing sagittal displacements between 2 mm and 17 mm were recorded in 14 patients. The largest displacements were obtained at different angles of inclination of the leg and flexion of the knee joint and were independent of the point of support of the knee joint. The reproducibility of this new standing technique was within 2 mm. A high correlation with previous methods of radiographic measurements of sagittal laxity was found. By the use of the normal relationship between the tibial eminence and the femoral condyles it is possible to record and measure sagittal displacements on a single lateral radiograph of the standing knee joint. PMID- 8480205 TI - Coexistence of calcific tendinitis and rotator cuff tear: an arthrographic study. AB - A prospective evaluation of the coexistence of calcific tendinitis and tear of the rotator cuff demonstrated by arthrography was made in patients presenting with shoulder pain. Patients were X-rayed using conventional views and impingement views. Eighty-one patients (mean age 61.2 years) with calcific tendinitis underwent arthrography. Arthrography showed 22 partial or complete tears of the rotator cuff. A small rather than a large amount of calcification was more likely to be associated with a rotator cuff tear (p = 0.005). The coexistence of calcific tendinitis with rotator cuff tear is not uncommon, especially in older age groups. PMID- 8480206 TI - Fractures of the occipital condyles: report of four cases and review of the literature. AB - Fractures of the occipital condyle are rare; 32 cases have been reported in the literature. Here, the authors describe four additional cases of occipital condylar fracture. Anderson's classification is used: type I fracture: comminution of the condyle without significant displacement; type II: basilar fracture extending into the condyle; type III: condylar avulsion. The possible mechanisms are identified. Computed tomography proved essential in diagnosing these fractures; coronal reconstructions together with axial scans are particularly helpful. Three-dimensional reconstruction did not prove essential in diagnosing these fractures. PMID- 8480207 TI - Slipped capital femoral epiphysis: ultrasonographic findings. AB - Slipped capital femoral epiphysis (SCFE) is an uncommon skeletal disorder of adolescence often overlooked because of its nonspecific clinical presentation. Anteroposterior radiography may fail to demonstrate a minimal slip even when clinical examination raises suspicion of the disease. On the other hand, prompt diagnosis is essential to obtain better therapeutic results. In our patient population joint effusion, which often accompanies SCFE, was readily recognized and quantified by ultrasonography (US). US also permitted recognition of the initial SCFE and assessment of the degree of slip by measuring the height of the physeal step. As to metaphyseal remodeling, plain radiography seems to be more informative than US; however, US has a role in the follow-up of SCFE because of the risk of slippage in the contralateral hip. This work suggests that US is useful as a primary imaging tool in the evaluation of subjects with limp or hip or knee pain to rule out SCFE. PMID- 8480208 TI - Predisposing factors in obstetrical fractures. AB - To compare various obstetrical methods with different types of obstetrical fractures, 29 neonates with fractures were evaluated retrospectively. Plain films of skull, limbs and chest were obtained. Transfontanellar ultrasonography was performed in one case and a computed tomographic scan of the skull in two. We reviewed 12 fractures of long bones, 7 fractures of the skull, and 10 fractures of the clavicle. Ten fractures occurred during caesarean sections and 11 in vaginal delivery requiring medical assistance. Depressed skull fractures were associated with manoeuvres and the use of forceps during delivery. Fractures of the long bones were associated with caesarean section, breech delivery with assistance and low birth weight. All fractures were treated conservatively except for skull fractures with depression of more than 2 cm. Early consolidation occurred in all fractures of long bones. The long-term follow-up of all fractures but one revealed no persisting disability. The belief that obstetrical fractures occur primarily in large babies or after breech delivery is not supported by this study. PMID- 8480209 TI - Case report 765. Von Gierke's disease. PMID- 8480210 TI - Case report 777. Osteolytic Paget's disease of the fifth lumbar vertebra. PMID- 8480211 TI - Case report 778. Melorheostosis presenting as two soft-tissue masses with osseous changes limited to the axial skeleton. PMID- 8480212 TI - Case report 779. Carbonate apatite calcification of ligamentum flavum. PMID- 8480213 TI - Case report 780. Fracture of talar beaks in tarsal coalition. PMID- 8480214 TI - Case report 782. Predominantly osteolytic Paget's disease of the calcaneus. PMID- 8480215 TI - Case report 783. Intraosseous ganglion of scapula. PMID- 8480216 TI - Health consequences of employment and unemployment: longitudinal evidence for young men and women. AB - This study examines the impact of employment and unemployment on psychological health and well-being, as measured by the General Health Questionnaire (GHQ). Using longitudinal data, it traces health changes over time for a variety of groups and through a variety of labour market experiences: during sustained employment and unemployment, in the transition from school to employment and unemployment, and as people move between employment and unemployment and between satisfying and unsatisfying jobs. The results show that employed people report significantly lower levels of health disorder than students and the unemployed. These differences are largely unaffected by demographic attributes, living arrangements, socioeconomic status or immediate labour market experiences, and can be attributed to employment status itself rather than predisposing health differences. However, the health consequences of employment and unemployment are directly contingent upon quality of work. As a result, the highest levels of health risk are found amongst dissatisfied workers and the lowest levels amongst satisfied workers. In between these two extremes lie employed people neither satisfied nor dissatisfied with their jobs, unemployed people irrespective of duration, and students. These results indicate that what happens in the workplace has even more impact on a person's health than success or failure in finding a job and keeping it. PMID- 8480217 TI - The structure and properties of the sense of coherence scale. AB - Previous work of the author presents a salutogenic theoretical model designed to explain maintenance or improvement of location on a health ease/dis-ease continuum. The model's core construct, the Sense of Coherence (SOC), was consciously formulated in terms which are thought to be applicable crossculturally. The SOC scale which operationalizes the construct is a 29-item semantic differential questionnaire, its design guided by Guttman's facet theory. A 13-item version of the scale has also been used. The purpose of the present paper is to present the extant evidence from studies conducted in 20 countries for the feasibility, reliability and validity of the scale, as well as normative data. In 26 studies using SOC-29 the Cronbach alpha measure of internal consistency has ranged from 0.82 to 0.95. The alphas of 16 studies using SOC-13 range from 0.74 to 0.91. The relatively few test-retest correlations show considerable stability, e.g. 0.54 over a 2-year period among retirees. The systematic procedure used in scale construction and examination of the final product by many colleagues points to a high level of content, face and consensual validity. The few data sets available point to a high level of construct validity. Criterion validity is examined by presenting correlational data between the SOC and measures in four domains: a global orientation to oneself and one's environment (19 r's); stressors (11 r's); health, illness and wellbeing (32 r's); attitudes and behavior (5 r's). The great majority of correlations are statistically significant. All available published normative data on SOC-29 and SOC-13 are presented, data which bear upon validity using the known groups technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480218 TI - Increasing reliance on user fees as a response to public health financing crises: a case study of El Salvador. AB - Since the early 1980s, the Ministries of Health of most Developing Countries have been plagued by significant and persistent resource shortages. One response of many Third World countries to this health financing crisis has been to turn to user fees. This article presents a case study of the evolution of public health care system fees in El Salvador in the decade of the 1980s. Since 1980 falling levels of real funding of the Ministry of Health of El Salvador have resulted in falling supplies of drugs, materials and equipment throughout the public health system, and have contributed to declining utilization levels of public health facilities. Local public health providers and their community health boards (patronatos) have responded to this crisis by creatively institutionalizing decentralized, revolving accounts based on 'voluntary' user fees for ambulatory care, collected and retained at individual facilities. This article describes the legal foundations, organization, functioning, incentive structures, financial performance, and the institutional development of El Salvador's local user fee systems. PMID- 8480219 TI - Suicide and unemployment in Australia 1907-1990. AB - Ever since Durkheim postulated a relationship between economic change and suicide there has been evidence of a general association between aggregate data on unemployment and the frequency of suicide. Quantitatively, however, the association has been variable and it is clear that due to differing cultural, social and individual determinants of suicide, the relationship is complex. Methodological difficulties abound with interpretation of aggregate data. Australian records for most of the present century are suitable for examining secular trends in suicide and unemployment by age group and gender to gain an indication of the extent to which both parameters may be causally related. An aggregate/ecological study was designed to incorporate quantitative and qualitative strategies. Annual age-adjusted male and female suicide rates and annual unemployment rates were derived for the period 1907-1990. Female suicide rates were generally stable throughout the period, whereas those for males demonstrated sharp fluctuations with the peaks coinciding with times of high unemployment. The association between suicide and unemployment for 15-24 year old males was comparatively high for the recent period, 1966-1990. The increasingly youthful contribution to male suicide was demonstrated by a rise in the loss of life years during 1973-1984. Despite the inability of any investigation based on aggregate data to establish an unequivocable causal relationship, no evidence was detected to suggest that relatively high population levels of unemployment were not related to the occurrence of suicide. PMID- 8480220 TI - Patient control over dying: responses of health care professionals. AB - Decisions concerning how, when and where patients should die have traditionally been the exclusive domain of health care professionals. More recently, patients and their families are demanding increasing control over these decisions. This paper reports on the responses of 20 physicians and 20 nurses in a major teaching hospital regarding the desire of patients to exert more control over the circumstances of their dying. The findings, based on in-depth, semi-structured interviews, suggest that while health care professionals are generally in favour of the principle of patient control over dying, they have reservations about accommodating patients' wishes in actual clinical situations. Key factors that underly their ambivalence on this point are: (1) specific patient circumstances, such as age, severity of illness and mental competence; (2) moral and legal concerns; and (3) the type of intervention requested by patient. The results indicate that patient control over dying represents a challenge to the clinical judgement of health care professionals; that it runs counter to their perception of their role as healers and supporters; that it raises crucial concerns about their personal ethics and legal liability and that it poses a challenge to their professional autonomy and power. It is likely that health care practitioners will increasingly be pressured to concede their autonomy and enter into a partnership with patients in the decision-making process. PMID- 8480221 TI - The attitudes of patients and physicians towards placebo treatment--a comparative study. AB - Placebo treatment in clinical practice can be given either in order to comply with the wishes of the patient, or with the purpose of doing good and not causing harm. In the former instance, the procedure may be in accordance with the interests of the patient, yet be in conflict with the interests of the medical profession. In the latter instance, the procedure presupposes that in most cases the patient has not been informed of the nature of the treatment; this type of procedure may jeopardize a trusting patient-doctor relationship. Therefore, it is of interest to investigate both the extent to which patients and physicians feel they can accept placebo treatment and a paternalistic attitude, and in which particular situations. In order to shed some light on this matter, we compiled a questionnaire built around three case histories which problematize placebo treatment and paternalistic acts. The questionnaire was distributed to 100 patients and 100 physicians. 83 patients and 94 physicians responded. The results show that patients and physicians do not automatically follow specific group interests. Physicians are more inclined to respect the patient's option to refuse medical treatment than the patients are inclined to respect a physician's professional autonomy. Patients appear more to be paternalistic in their judgements than physicians, but one cannot rule out the possibility that the answers of the physicians reflect the fact that placebo treatment represent a socially undesirable behaviour. We conclude that theoretical and normative analyses of the perspective of the actors ought to be supplemented by empirical research.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480222 TI - Primary health workers in north east Brazil. AB - One approach to providing primary health care in developing countries is to implement programs which rely on minimally trained primary health workers (PHWs). Originally, such programs were primarily designed for rural areas with intact social structures--where a community--based PHW could easily establish a link between the community and the conventional health services (delivery programs). However, faced with increasing migration of the rural population to urban centers in developing countries, the present need for elementary health care in urban slums raises the question of whether PHWs can also provide health assistance to the population there. This paper deals with the issue of whether PHWs in North East Brazil can improve health care delivery and the health situation of the poor population in rural and urban areas. The investigations covered both PHWs and the population. Questionnaire-guided interviews and participant observation were used as research tools. The conclusion is drawn that the PHW-program there has succeeded, if the PHWs have increased the coverage of the health service delivery and also the level of health-related knowledge, attitudes and practices (KAP) in the population--although with significant differences between rural and urban areas (higher coverage and higher KAP in rural areas). The quality of training and supervision and the characteristics of the area and local framework were also found to influence the quality of the work (performance) of the PHWs. PMID- 8480223 TI - Social science and the study of pain since Zborowski: a need for a new agenda. AB - In 1969, anthropologist Mark Zborowski published People in Pain, in which he showed that pain is responded to by behaviors and attitudes learned by pain sufferers within the cultures in which they are socialized. Research for this work was accomplished at a time when a number of social scientists were deeply involved in inquiry about the relationship between the individual psyche and society, and were, therefore, interested in subjective experiences of individuals. For reasons discussed in this article, social researchers shifted their focus, in the late 1960s and throughout the 1970s, from the study of subjective experience to research pertaining to more objectively verifiable phenomena. Consequently, because pain is not easily measurable, relatively few studies illuminating the human experience of pain were performed by social scientists since Zborowski completed his work. This article provides an overview of the small but pertinent research that has been conducted since the late 1960s, and challenges social scientists to develop a new agenda for the study of pain experiences. This research may be especially timely now, when there seems to be renewed interest among social scientists to study subjective experiences. PMID- 8480224 TI - Witchcraft-explained childhood tragedies in Tlaxcala, and their medical sequelae. AB - This paper describes results of a study in Tlaxcala, Mexico, involving the sudden death of infants and children that culturally are explained as resulting from the attack of blood-sucking witches. The attacks of the supernaturals are relatively common occurrences and an elaborate ideology has evolved to explain them. Such an ideology serves to explain what constitutes a major trauma of loss and supernatural assault. Data on a total of 47 cases were collected prospectively. The illness experiences of the parents following these traumas were recorded and their nature and consequences analyzed. The results of the study provide a 'folk medical' epidemiology of sudden infant death, a well identified cultural ecological stressor. Ideas from cultural, psychological and medical anthropology as well as general medicine and psychiatry are used in the interpretation of the results. PMID- 8480225 TI - Socioeconomic, environmental, demographic and behavioral factors associated with occurrence of diarrhea in young children in the Republic of Congo. AB - This study is the result of a cross-sectional survey undertaken in five regions of the Republic of Congo. A sample of 612 women having children under 3 years of age was interviewed to determine the socioeconomic, environmental, demographic and behavioral factors associated with the occurrence of diarrhea in young children. Logistic regression analysis was used to determine which variables predict the occurrence of diarrhea in a multivariable context. Most of the statistically significant variables were those suggesting behaviorally mediated modes of transmission. These include: type of weaning food fed to the child, maternal age, sex of the child, maternal sickness and method of refuse disposal. Male children had a more than two-fold odds of experiencing recent diarrhea than did female children among those greater than 1 year of age. Although breastfeeding status was not statistically significantly associated with diarrheal disease, children under 1 year of age who were already weaned had a greater odds of disease than those who were still breasted. Due to the pattern of extended breastfeeding in this population, this relationship was difficult to assess. Urban residence also was highly associated with diarrheal disease occurrence. Urban residence is likely to reflect a host of socioeconomic, environmental and behavioral factors. These findings underscore the potential impact of educational interventions on the occurrence of diarrheal disease among young children. PMID- 8480226 TI - Prevalence of smoking in physicians and medical students, and the generation effect in The Netherlands. AB - This study investigates smoking habits and attitudes towards smoking in general practitioners, consultants at a university hospital, medical students and students of health policy and management (H.P.M.). An anonymous, self administered postal survey was used. Thirty-eight percent of the general practitioners, 27% of the consultants, 18% of the medical students and 31% of the H.P.M. students are current smokers. The prevalence of smoking was found to be higher in the male general practitioners and the male H.P.M. students than in the general male population. The prevalence of smoking was lower in female physicians and students than in their male counterparts and also lower than in the general female population. Medical students are not inclined to start smoking: a strong generation effect can be observed. This will reinforce the current downward trend in the prevalence of smoking in Dutch physicians. The doctors were found to have a suboptimal level of knowledge about methods of smoking cessation and about the association between smoking and health disorders. Most Dutch physicians, especially those who smoke, fail to perceive their role as an example to the general population concerning smoking behaviour. Medical students were found to have even less recognition of their future exemplary role. PMID- 8480227 TI - What do students find attractive about the practice of medicine? A pattern of stability over time. AB - There is little consensus about the stability or instability of medical students career preferences during their time in college. These two studies found little change in their perception of the attractiveness of aspects of medical work which may be related to their final career choice. In the first study three successive cohorts of students in a London medical school completed questionnaires about the attractiveness of various medical job-attributes. Each cohort was tested twice such that the pattern of testing covered the entire course. Only data from students who were present at both test sessions were used for the longitudinal study. Comparisons with students in other London schools indicated that the study groups were representative of all London medical students. The second study was cross-sectional comparing final year data from 1983 and 1991 at three London medical schools. The first study results suggest that students enter medical school with values and opinions about their work which remain, on the whole, unchanged until they leave. There were significant decreases in the attractiveness of four attributes, but none became significantly more attractive. The second study revealed little change, five attributes were significantly less attractive 8 years later. In both studies most of the changes related to organisational rather than patient-related attributes. This may reflect greater realism about doctors' work. Comparison of final years students' data with published data from the mid-seventies confirms the overall stability of these values. It is suggested that specialists could use this information to highlight the desirable aspects of their work and so 'sell' their discipline to students and newly qualified doctors. PMID- 8480228 TI - Methodology of dietary investigation. PMID- 8480229 TI - W.H.R. Rivers and the anthropology of psychiatry. PMID- 8480230 TI - The impact of war on children's health in Mozambique. AB - Since 1982, South African destabilization of Mozambique has caused children's health to deteriorate. Destabilization has functioned through support of a surrogate movement and economic pressure. Attacks on economic and civilian targets have included the health services, leading to closure of 48% of the primary health care network. The war has caused displacement of over 3,000,000 persons and an estimated 494,000 excess childhood deaths between 1981 and 1988. An estimated 200,000 children have been separated from their families or orphaned; many children have also witnessed atrocities and suffered violence. A deepening economic crisis has been followed by an economic structural adjustment programme. Responses to the war include changes in vaccination strategy and programmes to reunite families and heal psychological trauma. PMID- 8480231 TI - Obstacles to medical audit: British doctors speak. AB - Currently, British doctors are being encouraged by government, managers and their professional associations to undertake medical audit. How easy a task will it be to introduce audit? In an attempt to find out, doctors working in general, geriatric and accident and emergency medicine in four district general hospitals were interviewed. Twenty-eight consultants and 34 junior doctors participated. Generally speaking, doctors accepted the need for audit. In this paper we have focussed deliberately on their worries, since it is these which are of most importance in developing better methods of implementation. The 19 obstacles to audit that respondents identified can be grouped into four categories: perceptions of the need for and the role of audit; practical considerations; the effects of audit; and anxieties about the use of audit. In general, criticisms were levelled at the way audit was being implemented rather than at the principles of the approach. While some obstacles could be overcome by simple, practical measures, others will require a change in doctors' knowledge, beliefs and attitudes. The difficulty of achieving such changes should not be underestimated. PMID- 8480232 TI - The body: from an immateriality to another. AB - A first level of immateriality of the human body is very classic for anthropologists: it concerns the different conceptions of soul, of a supernatural component of the human being. It refers also to different kinds of continuity and exchange between the human body and society. The other immateriality appears as an answer to the biological reductionism of the body. As we can see in biomedical conception of the body, as well as in different totalitarian utopias, biological reductionism tends to reduce the whole person to its biological body. Consciously or unconsciously, people cannot accept it. Contemporary ways of healing reflect this contradiction: people accept biological knowledge but they do not accept a purely biological conception of their own body. They conceive that there is an immaterial part in the human body; however it is not supernatural but a part of nature. In this way this 'not divine immateriality' can be conciliated with some kind of scientific approach. The refusal to enclose the person in the biological body appears as a constant through human societies. At the medical level, this refusal is always present in the ill person's image of his body and of his illness. At a more general level, this refusal is probably necessary in order to keep human freedom as well as human specificity. PMID- 8480233 TI - Child health and the social environment of white and black children. AB - Both poverty and other factors associated with race are related to child health. However, the mechanisms of these relationships have not been adequately specified. The purpose of this study was to explore the relationship of the social environment to child health status in black and white children and further, to explore whether the patterns of the effects of social class were different by race. This study provides further evidence that the social environment is strongly associated with child health status. Several risk factors are similar for both white and black children: mothers who view their own health as fair or poor are much more likely to rate their children in poor health. The presence of childhood chronic medical conditions is independently associated with poor health status regardless of race. However, the relative importance of several social risks for poor health status differs between white and black children. Specifically, while low family income is a consistent risk factor for poor health among white children, low income alone is not a risk factor for black children. Among black children, other social risks that are associated with poverty, such as low maternal education and a mother's perception of her own health as poor, increased the risk of poorer health in the child. PMID- 8480234 TI - Societal and ecological determinants of urban health: a case study of pre reproductive mortality in 19th century Gibraltar. AB - A historical based enquiry of colonial Gibraltar at the turn of the 19th century was conducted in order to assess what factors gave rise to residential variation of pre-reproductive mortality. Gibraltar's unusual configuration of a port city, garrison town, and commercial centre at the tip of the Iberian peninsula offers a unique opportunity to examine the interplay of ecology, demographic and socio economic factors on childhood mortality. Communal living under the patio system and the sharing of essential resources were characteristic features of life on the Rock. Using the residential district as the focus of enquiry, stepwise regression results for the period 1879-81, designated as a period of 'low ecological stress', indicated that the number of gallons of potable water per person captured a significant amount of variability in mortality. During the year 1878, a serious shortfall in rainfall was associated with lower life expectancy, a change in the seasonal pattern of mortality, and elevated rates of death attributable to the diarrhea complex. Under this period of 'high ecological stress', the percentage of servants in the household, a proxy for wealth/status, proved to be the single most important factor accounting for 46.6% of the variation in the death rate under 15. Analysis of mortality at the patio level revealed that residents of buildings of two household units had lower mortality than residents living in smaller or larger dwellings, particularly in the period of high ecological stress. The complex pattern of mortality at the district and patio level is explained in terms of the development of residential preferences and decentralized nature of vital resources, such as the water support system and food supply. PMID- 8480235 TI - Anti-permissive attitudes to lifestyles associated with AIDS. AB - AIDS is in the tradition of diseases which have given moral interpretations. One way in which this moralistic perspective may express itself is by members of the public holding high risk groups responsible for their (AIDS related) lifestyles and their considering AIDS to be a self-inflicted disease. A unique data source of 7000 verbatim comments recorded in the course of 25,000 structured Computer Assisted Telephone Interviews on Lifestyle and Health which contain a substantial component on AIDS--knowledge, attitudes, beliefs and sexual behaviour, was used to document negative attitudes to 'AIDS related lifestyles'. These comments revealed that despite evidence of concern about drug use, many respondents consider AIDS to be irrelevant to the majority of the population. There is some evidence that AIDS has contributed to reinforcing negative attitudes towards homosexuality and drug use, especially among older respondents. Extreme punitive attitudes towards high risk groups were expressed by a small minority (predominantly males). PMID- 8480236 TI - Health related response to natural disasters: the case of the Bangladesh cyclone of 1991. AB - This paper evaluates the health related response to large natural disasters using the example of the recent Bangladesh cyclone of 1991. After providing a description of the extent of the health response, it focuses on three major issues: (i) assessment of needs (ii) coordination of major groups involved in health relief and rehabilitation efforts and (iii) appropriateness and effectiveness of the health response in terms of definable outcome criteria. The conclusions are that in the case of the Bangladesh cyclone: (a) the assessment of needs was more reactive rather than anticipatory and was not based on any systematic data gathering from the field; (b) in contrast to previous disaster situations there was excellent coordination of the major groups involved in the aid process (the government, the armed forces and non-governmental organizations) and (c) given the caveat of inadequate baseline information, it appears that the health response was prompt and effective in preventing any increase in mortality from diarrheal diseases and measles. The reasons for the deficiencies and successes of the health response are analysed and finally a list of detailed recommendations to facilitate future disaster/cyclone management and response is provided. PMID- 8480237 TI - Towards understanding treatment preferences of hospital physicians. AB - Seventy-two physicians working in a university hospital in The Netherlands were interviewed to clarify their decision-making process when choosing drugs of preference. Each physician was questioned about the treatment choices for either one or two general case descriptions. The physicians considered only a limited set of different treatment options, on an average 1.7-5.0. Further, the physicians expressed their expectancies as regards various treatment alternatives, and the value or weight they attached to the principle aspects of a treatment. An analytical decision model was used as a reference to gain insight into the extent to which the physicians make decisions based on their own subjective expectancies and values. This model assumes that physicians follow a maximizing strategy by choosing the treatment they personally assess as optimal. It was found that a model including only biomedical expectancies and values predicted the preferred treatment correctly in no more than 53% of the cases. Sometimes, biomedical aspects were disregarded that should have been relevant according to the physicians themselves. Adding aspects of the social environment and experiences improved the prediction of the model substantially; 3 out of 4 treatment preferences could be understood by following an analytical maximizing strategy including biomedical aspects and social aspects and experiences. In the remaining cases, the physicians were not able to describe their decision in terms of this maximizing strategy, which points at the use of alternative decision strategies. One alternative decision strategy mentioned by the physicians was a 'follow-the-routine' decision rule. PMID- 8480238 TI - Maternal education and child feeding practices in rural Bangladesh. AB - This study in rural lowland Bangladesh used spot and event observations from 185 children aged 4-27 months in order to examine whether child feeding practices differed with mother's education and with household education. Each child and his/her caretakers were observed for a mean of 20 hr over 6 months from February to July 1986. Only 25% of mothers and 51% of fathers had had any formal education. Exploratory partial correlations and stepwise multiple regression analyses revealed significant behavioral differences with both maternal and household measures of education while controlling for wealth. Caretakers in families with education were found to feed the children more frequently, with fresher food, and in cleaner, more protected places. They did not allow their children to eat food intended for someone else as often, and were more observant when their children's food dropped during the feeding. These caretakers also used more cups and bottles for feedings, breastfed their children less frequently, and their mothers terminated the breastfeedings more often. These behaviors suggested a shift from less attentive feeding practices and less frequent feedings to more frequent feedings in which the caretaker took more control of the child's feeding sessions. They also suggest a commitment to more labor-intensive child care. These associations between education and child feeding practices are mechanisms through which maternal education may improve child health and growth. They suggest the need for promoting more formal and nonformal education. PMID- 8480239 TI - Child feeding practices in a rural area of Zimbabwe. AB - This paper reports preliminary results from a study of child feeding practices in a rural area of Zimbabwe. Although Zimbabwe has relatively low infant mortality rates, it still has high child malnutrition rates. Several factors, including sex roles and relations between the sexes, access to resources, food costs and availability, time and energy costs of food production and preparation, and illness beliefs and practices, especially those concerning diarrhea and malnutrition, are examined as possible determinants of feeding practices and nutritional and health status. Results are compared to reports made by the World Bank and the Zimbabwe national nutrition survey. Whereas the World Bank report suggests a problem of late introduction of breastmilk supplements or solids, we found the opposite tendency of early introduction (by 3 months) of supplements. We suggest that mothers' pragmatic attitudes, interacting with certain social, cultural, and economic variables, are important factors influencing their child feeding decisions, especially resisting the use of commercial infant formula, at least in this rural area, and promoting prolonged breastfeeding. PMID- 8480240 TI - HIV transmission through social and geographic networks in Uganda. AB - Long distance drivers and prostitutes at trading centres and towns have been targeted as groups that engage in risky sexual behaviours that promote HIV transmission. While towns and stops along highways have been linked to HIV transmission, the role of small urban and rural centres have been overlooked. There is need to study socio-geographical mating networks because situations not deemed to be risky may be an important aspect of HIV transmission. PMID- 8480241 TI - Interfacing anthropology and epidemiology: the Bedouin Arab Infant Feeding Study. AB - This paper encapsulates a 10 year effort of multi-disciplinary research on the relationship between infant feeding, growth, and morbidity among the Negev Bedouin Arabs of Israel as they underwent a transition from semi-nomadism to urban settlement. The research team was multi-disciplinary including a nutritional epidemiologist and an anthropologist who both came to the study with previous experience in interdisciplinary work. The specific study objectives were (1) a description of infant feeding practices among Negev Bedouin Arab women at various stages of settlement, (2) an examination of the trend in these infant feeding practices, (3) a comparison of the extent to which different infant feeding practices are related to infant morbidity and growth after adjustment for exposure to social change and other covariates. The data collection took place in 1981-83 and the analysis from 1984-88. In this paper, two areas of the study are discussed in depth: the duration of exclusive breast feeding during the practice of the traditional postpartum 40 day rest period, and the development of a culture-specific scale of socioeconomic status. Through these examples, we highlight the use of ethnographic data and the merging of epidemiology and anthropology from hypothesis generation through data collection, data analysis and interpretation. PMID- 8480242 TI - Prostitution and the military: planning AIDS intervention in Belize. AB - First world militaries based in 'third world' countries offer an appropriate context for developing AIDS intervention models that are keyed to large-scale population movements and regional differences in HIV infection. In this work, the ethnographic concept of 'social interface' replaces the epidemiological concept of 'risk group' to allow for a more dynamic analysis of the particular forms of interactions between groups that may be linked to the sexual transmission of HIV. The social interface between military and sex workers in Belize displays two distinct forms of organization: (1) 'recognized prostitution' in health-regulated brothels, and (2) 'quasi-prostitution' in non-health regulated public sites such as bars and hotels. These two forms are also distinguished by the ethnicity, national origin, and professional identity of sex workers. Based on survey-form participant-observation in Belize and cross-cultural data on condom use, the social identity of sex workers emerges as a factor crucial to understanding how public health information is incorporated by heterosexuals who put themselves at risk for HIV in different social contexts. The scope of analysis shifts between the personal and transnational; discussion of the possibilities for inter governmental negotiations regarding AIDS policy issues is included. PMID- 8480243 TI - Role conflict: cause of burnout or energizer? AB - A year-long study of public child welfare administrators examined the effects of role conflict on their attitudes and performance. Popular belief and some of the literature have suggested that burnout is inevitable for those confronted with role conflict. Other literature has proposed that it may instead be energizing to individuals and lead to greater personal and organizational effectiveness. This qualitative study found that individuals in the study had developed specific, effective skills for responding to role conflict. Although there was a public presentation of self that indicated they were under stress and in "impossible" situations, there was in fact an energizing effect resulting from the ongoing challenge of dealing with conflict. PMID- 8480244 TI - Facilitating support groups for professionals working with people with AIDS. AB - Social workers, nurses, and other health care professionals who work with people with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) are experiencing burnout from the excessive demands on their energy, strength, and resources. Support groups, with their focus on awareness, shared experiences, supportive and helping relationships, and the emotional consequences of working with people with AIDS, help health care professionals manage stress and enhance their capacity and effectiveness to work with these clients. In addition, support groups help participants feel less isolated and share feelings regarding such difficult issues as death, anger, helplessness, and loss. The use of this type of group work is identified, including its administration, effective intervention techniques, and issues of health care professionals who work with the HIV/AIDS epidemic. Problems related to group membership and dropout rates are explored as unresolved issues. PMID- 8480245 TI - Effects of social support and undermining on African American workers' perceptions of coworker and supervisor relationships and psychological well being. AB - Although social undermining is a commonly experienced stressor in human services workplaces, it has received little study in contemporary models of social work stress and burnout. Furthermore, African Americans currently make up nearly 25 percent of self-identified social workers in the United States, yet most literature on personnel relationships in human services does not reference this group. Data collected from a national sample of 288 African American members of the National Association of Social Workers were used to investigate the impact of undermining among coworker and supervisor-supervisee relationships. Multiple regression analyses revealed substantial increases in irritability, depression, anxiety, and depersonalization among social workers when social undermining was included in a set of predictor variables (age, gender, and social support). The presence of social support, however, did not diminish the impact of undermining. The authors discuss several practice and training implications of these findings. PMID- 8480246 TI - Classification and correlates of ethical dilemmas in hospital social work. AB - The authors used categories based on the NASW Code of Ethics to code hospital social workers' descriptions of ethical dilemmas according to the specific principles in conflict. They also developed codes to identify discharge destination and medical care issues involved in the ethical dilemma. Most ethical dilemmas were found to involve conflicts between client self-determination and client best interest. Ethical dilemmas were more likely when patient mental status was impaired and when decision making was problematic. Ethical dilemmas were related to delayed discharge, in-hospital mortality, and less-than-adequate postdischarge care. The study enhances understanding of ethical dilemmas and advances a methodology for studying their occurrence and consequences. PMID- 8480247 TI - Record keeping: directions for the 1990s. AB - In studies conducted in the late 1980s, managers and direct service workers agreed that their biggest record-keeping problems were caused by lack of time. This article describes how 114 agencies in 20 states tried to resolve this problem Agencies were more successful when they simplified recording and allocated new resources to the task. This article outlines the techniques these agencies used and contrasts those that were more successful with those that had mixed or poor results. The findings suggest directions for record keeping in social services agencies in the 1990s, when agencies will face critical choices about how to use limited resources. PMID- 8480248 TI - Suicide prevention: a classroom presentation to adolescents. AB - The increase in attention given to adolescent suicide has led to a proliferation of suicide prevention programs in schools throughout the United States. Concern is mounting over the benefits of these programs. The author, with the same concern about his own suicide prevention program, subjects his program to a statistical analysis of effectiveness. Results show that a disturbingly high proportion of adolescents had undesirable attitudes about suicide in the baseline period. The program appears to have caused a significant shift from undesirable to desirable attitudinal responses in six of eight targeted areas. In addition, the results seem to dispel a commonly held belief that associating mental illness with suicide will diminish self-disclosure. PMID- 8480249 TI - Misdiagnosing assessment. PMID- 8480250 TI - [The right to health among all individuals and social groups is an exigency of man and a responsibility of the state and of society]. PMID- 8480251 TI - [The Free Trade Agreement and environmental health in Mexico]. AB - This work offers an overview of the state of the art and future state of environmental health in our country from a viewpoint of the impact of the commercial opening established in the Free Trade Agreement among Mexico, the USA, and Canada. In the first section of this work, we analyze the expected economic changes resulting from the implementation of the FTA and foretells the way in which those changes will influence the present environmental and epidemiologic profiles of this country in the medium and long term. The main changes predicted by the analysis are, in the epidemiologic context, the acceleration of the transference of occupational, consumption, environmental and population risks, characteristic of industrialized countries, to the country's polarized epidemiologic profile; and, in the environmental context, a transition consisting of a broadening and composition of the spectrum of pollutants, including and important lagging of bacteriologic control. The second section offers an analysis of the predicted response capacity facing the new environmental risk dynamics in the country, encompassing regulation, normativeness and enforcement of environmental and consumer protection, as well as obstacles found in health services to the implementation of surveillance, detection and treatment of health damages caused by environmental factors. The analysis of the organized social response to these problems discloses a relative flexibility of the normativeness and enforcement functions in comparison with our northern neighbors, a paramount factor for the possible transference of environmental risks, as well as the informational and research deficiency about environmental issues, basic elements for sustaining environmental health in the country, aiming at speeding up the development and transference of technologies for prevention, detection and management of environmental risks in the country, drawing upon the systematization of our experience and that of our neighbors. This speeding process ought to match, in the medium term, the velocity of risk transference produced by the commercial opening. In this way, the commercial integration of North America will become a favorable context for the development of the environmental health infrastructure of the country. PMID- 8480252 TI - [Mortality in young adults: international comparisons]. AB - In searching for an epidemiological indicator which might reflect the impact of the widespread use of various drugs among California youth in the late 1960s, the customary sources of health statistics were found to be unsatisfactory due to the lack of consensus on diagnosis of drug related problems. Examination of mortality of young adults (persons aged 15-24, YAM) showed marked and paradoxical rises when drug use was rising. Males and Blacks had higher rates than females and Whites; motor vehicle accidents were the largest single overall cause. But the rise, both in California and the US was proportionally greater among women and motor vehicle accidents did not contribute to the rise. Examination of rates during mid-1970s for various countries showed that for countries with per capita income less than about $3,000 per year, YAM due to diseases was very closely correlated with per capita income. Above that external cause, YAM and particularly that due to motor vehicle accidents, increased with per capita income. The increase was steeper in some countries than in others. The difference in these two groups of countries was correlated with fraction of national income spent on education and with ethnic homogeneity. In the US fluctuations in YAM paralleled admissions for heroin use. As part of the Epidemiological Revolution, young adult mortality complements infant mortality, since it is closely related to social health, employment opportunities and appropriateness of education. Further, it is important for the potential development of a country, region, or community. This report examines YAM data for mid-1980s from selected countries and notes major changes during the past decade, most countries having shown striking decreases. In some countries high rates of suicide, homicide and death due to civil disorders provide an incentive for further improvement. In other countries, the high rates for death attributed to motor vehicle crashes compels attention. Involvement of young persons themselves in plans for improvement of their opportunities seems an essential strategy, for which the educational strategies suggested by Freire seem to be appropriate. PMID- 8480253 TI - [Women and violence: an everyday fact]. AB - In comparison with other countries, Mexico lacks information on the issue of violence against women, especially regarding the incidence and prevalence of battering and emotional abuse. The aim of this study was to determine the frequency and distribution of violence against women among both rural and urban populations in the state of Jalisco, Mexico. A cross-sectional study was conducted among two groups randomly selected; 1,163 rural women (RW) and 427 urban women (UW). Variables included: frequency of violence of family members against women and vice versa, socioeconomic variables and reason for violence. The results were: a) 44.2 per cent and 56.7 per cent rural and urban female population, respectively, suffered some form of violence; b) the principal aggressor was the husband in more than 60 per cent of the cases in both rural and urban areas. Significant statistical difference (p < 0.05) were found between rural and urban groups in relation to low education, middle-age and family size over 7 members. PMID- 8480254 TI - [Patterns of medical prescriptions for individuals with diabetes mellitus type 2 at the primary care level]. AB - A cross-sectional study was conducted to investigate the prescription patterns of general practitioners for non-insulin dependent diabetes mellitus patients in Guadalajara, Mexico. Two hundred and forty medical prescriptions were evaluated. These were indicated by 16 primary care physicians. Results showed that physicians prescribed pharmacologic agents in 93 per cent of the cases, dietary control in 73 per cent, and physical exercise in 48 per cent. A combination therapy of these three measures was employed in 40 per cent of the patients, but the combination regimen of diet and exercise was given only to 3 per cent of the patients. Data showed significant differences in prescribing patterns according to gender of physicians; male physicians prescribed the three measures by more than 10 per cent; On the contrary, female physicians prescribed the drug as the only therapy 27 per cent of the time. The proportion of prescribing diet and exercise measures increased with more years of professional experience. These observations support the findings that prescription patterns by primary care physicians do not meet the criteria currently recommended by international committees for diabetes therapy. We discuss some implications for the metabolic control of the disease and the quality of medical care. PMID- 8480255 TI - [A self-care group in diabetes mellitus type 2]. AB - The present work presents the experience of a diabetes self-care group in San Antonio Tecomitl, Milpa Alta, D.F., Mexico. Diabetes is a serious disease posing a public health problem in our country, since it affects a great number of productive age persons, causing, if uncontrolled, deleterious effects on their life quality and expectancy because of vascular and neural complications. We carried out an intervention in six female patients diagnosed as having diabetes mellitus type II, with different stages of the disease; all of them were residents of Milpa Alta municipality, with an average age of 63.6 years. They were receiving different doses of oral hypoglycemic agents. The group of patients met once a week for two-hour sessions in which they received: a) information about diabetes mellitus, b) self-care training and c) profound relaxation techniques. In each session we evaluated glycemia, body weight and blood pressure in each patient. Results from the intervention showed no correlation between body weight and blood pressure, though there was a significant variation in glycemia levels after the intervention. PMID- 8480256 TI - [The use of personal computers and health damage in the workers of a daily newspaper]. AB - We present the results of a research work carried out in 1989 in newspaper workers in Mexico City. This research was supported by the worker's Union. The main objective was to identify health occupational problems related with the use of personal computers (PC). The results of this work intended to be used for promoting preventive measurements to be included in the worker's contract. We found some evidences of an association between the use of PC visual fatigue and muscle pain as well as of an association between myopia and astigmatism, although it was not possible to demonstrate their relationship with PC. However, the chronic evolution of visual fatigue can induce refraction problems. In relation to the presence of stress and its subjective symptoms, we confirmed that the existence of psychological and physiological symptoms were greater in workers that use PC. It was also observed that these subjective symptoms have a very close relationship with the work contents more than with the use of the PC itself. PMID- 8480257 TI - [The privatization of public services. The case of health services in Costa Rica]. AB - This article analyzes the role of the State and public enterprises in the development of nations, from a particular standing point, and inquires into the privatization issue, reviewing both its concept and the possible mechanisms for its implementation. Also, emphasis is made on the selling of public enterprises as one of the several ways to privatize. Within this context, some measures for the reorganization of the Costa Rican National Health System are proposed. These measures uphold fundamental values of social justice. This article is based on a theoretical-conceptual framework from an innovative experience in health services management in Costa Rica, in which a self-managing cooperative society (a nonprofit enterprise) manages, by contract with national health care public institutions, an urban local health care system. PMID- 8480258 TI - [The validation of qualitative nutritional indicators: the Guttman Scale vs the customary diet]. AB - The purpose of this study was to assess the validity and feasibility of using the Guttman Scale as an indicator of usual dietary intake. Validation was done by comparing the results of dietary intake of a population obtained by using the Guttman Scale with a well-known method for evaluating dietary intake: the dietary history (one week). The study was done in seven communities in the state of Puebla, Mexico. Results from this study showed a weak correlation between the Guttman Scale with socioeconomic status and nutritional status. However, the results obtained with the dietary history method had a significant relationship with socioeconomic status and nutritional status. The conclusions are that the Guttman Scale has limitations when it is used as an alternative to the dietary history method for evaluating the total caloric intake, though it can be useful to determine dietary patterns of the individual. PMID- 8480259 TI - [An evaluation of the new program of Master of Sciences in Environmental Health]. AB - Our country is presently undergoing a historical, environmental and economic transition, along with an intense industrial expansion. As the rapid industrialization has not run parallel with the strengthening of environmental sanitary infrastructure, metropolitan cities have grown anarchically, turning over excessive amounts of air, water and soil pollutants. The harmonic combination of development, environment and health requires the supervision of trained human resources. The scarcity of such resources is a major restriction to overcome. In response to the lack of human resources devoted to environmental issues, the School of Public Health of Mexico established the Specialty of Environmental Health. In coordination with experts and decision makers from the health services, this specialty was reorganized in a Master of Science Degree in Environmental Health. Several institutions participated in this program actively, either with financial support or with human resources. The major obstacle to the continuity of the Program has been the lack of institutional financial support for students to devote fully to the programs. Nevertheless this Master's Degree is expected to undergo intense development in coming years. In the future, this program will have to reduce its epidemiologic focus and adopt a more general one. Efforts will be directed toward a wider national and international projection. PMID- 8480260 TI - [Bioethics and environmental health]. AB - Institutions such as World Health Organization and United Nations have considered the necessity to establish programs to control and preserve our environment. From the beginning, industrial development has polluted the air, water and soil, in some cases irreversibly affecting the ecosystems. Rampant use of natural resources and inattention to preventive measures have promoted environmental pollution, along with its hereditary effects, producing brain damage, intoxications, cancer, and respiratory and cardiovascular conditions, among other problems. It is necessary to put aside self-serving materialism and individualism and become aware of this problem. It is necessary to implement environmental policies, foster bioethical responsibility in environmental health research, conduct epidemiologic, biomedical and toxicologic environmental health research works if we are to have a worthy life and an optimal environment. PMID- 8480261 TI - [Historical and practical treatise on vaccines. 1803]. PMID- 8480262 TI - Intraoperative cholangiography for laparoscopic cholecystectomy. AB - Intraoperative cholangiography in the course of laparoscopic cholecystectomy is not only valuable to detect common bile duct stones, but also to delineate the anatomy of the biliary ducts, facilitate the dissection, avoid injuries to the biliary tract and identify other abnormalities, such as fistulas, cysts and tumors of the biliary system. Most surgeons use a variation of the transcystic injection of contrast. We describe herein a technique of cholangiography through the gallbladder, performed before starting any dissection in the cystic duct area, which has resulted in a rate of 92 percent of adequate cholangiograms and has proved to be easier, by far, and safer than the transcystic technique. A comparison was made between 405 instances of open cholecystectomies and 200 laparoscopic cholecystectomies with transcystic cholangiograms and 105 laparoscopic cholecystectomies with cholangiograms done through the gallbladder. All instances were done for symptomatic chronic or acute calculous cholecystitis. Satisfactory cholangiograms were obtained in 95 percent of open cholecystectomies and in only 68 percent of transcystic laparoscopic attempts. Complications and false-positive findings were seen in transcystic laparoscopic procedures in five and six instances, respectively. Cholangiography performed through the gallbladder was 100 percent successful among 73 patients with chronic cholecystitis and in 66 percent of 32 patients with acute calculous cholecystitis. For optimal visualization of the bile ducts, it is essential to exert pressure on the gallbladder after the injection of contrast to advance the contrast through the cystic duct. This is greatly facilitated by the use of a double-balloon catheter to avoid leak at the site of the gallbladder puncture. PMID- 8480263 TI - Increasing antibiotic dose decreases polymicrobial infection after hemorrhagic shock. AB - Hemorrhagic shock has been shown to increase the susceptibility to infection despite the administration of conventionally accepted doses of antimicrobial drugs. The efficacy of increasing antibiotic dose in a model of mixed gram negative infection, both with and without hemorrhagic shock, was examined. Shock was induced by bleeding rats to a mean arterial pressure of 45 millimeters of mercury for 45 minutes followed by resuscitation with shed blood and saline solution. One hour after shock or sham, the rats were inoculated with 1 x 10(8) Escherichia coli plus 1 x 10(9) Bacteroides fragilis in a fecal suspension subcutaneously. Rats were given either no antibiotic (CONTROL) or cefoxitin at 30 milligrams per kilogram (STANDARD) or 200 milligrams per kilogram (HIGH) intraperitoneally, 30 minutes before and at six and 12 hours after inoculation. Tissue cefoxitin concentrations were measured 30 minutes before and at six and 12 hours after inoculation. Tissue cefoxitin concentrations were measured 30 minutes after the initial dose. STANDARD reduced abscess diameter by 58 percent compared with CONTROL in rats that were not shocked, but only by 26 percent after shock (p < 0.05 shock versus sham). HIGH further decreased abscess diameter and weight (4 +/- 1 millimeter and 22 +/- 22 milligrams) after shock compared with STANDARD (9 +/- 1 millimeter and 230 +/- 90 milligrams; both p < 0.05). Peak tissue cefoxitin levels were greater than 19 times the minimal inhibitory concentration for each bacteria for HIGH compared with eight times for STANDARD. These data demonstrate that an increased dose of cefoxitin was superior to a conventional dose in controlling a mixed gram-negative infection after shock and suggest that altering traditional antibiotic use may decrease the incidence of infection after shock and hemorrhage. PMID- 8480264 TI - Ketorolac and patient controlled analgesia in the treatment of postoperative pain. AB - Ketorolac tromethamine (Toradol [Syntex, Palo Alto]), a new commercially available nonsteroidal antiinflammatory drug (NSAID), has appropriate solubility and minimal tissue irritation, making it suitable for intramuscular injection. Previously, NSAID have only been available for oral use in the United States for the treatment of pain. Ketorolac, the most potent NSAID known, relieves pain through inhibition of arachidonic acid synthesis at the cyclooxygenase level and has no central opioid effects. The results of previous studies using parenteral ketorolac in combination with patient administered narcotics have shown a 40 percent reduction in narcotic requirements. However, ketorolac is presently only approved for intramuscular injection and oral use in the United States. In a prospective, randomized study, we compared intramuscular ketorolac in combination with patient controlled intravenous narcotic analgesia (morphine) (PCA-M) to PCA M alone for the control of pain after extensive colonic resections. The combination of intramuscular ketorolac and PCA-M provided equal pain relief with no increased side effects when compared with narcotics alone. However, narcotic requirements of the patients were decreased by an average of 45 percent. Ketorolac and narcotics in combination provide effective postoperative pain relief and significantly decrease narcotic requirements. This combination may be particularly beneficial in the subpopulation of patients especially prone to narcotic related complications. PMID- 8480265 TI - Hysteroscopic metroplasty with resectoscope or microscissors for the correction of septate uterus. AB - During 1990, we performed hysteroscopic incision of uterine septum in 23 women with repeated abortion. The patients were allocated randomly to metroplasty with resectoscope (12 patients in group 1) or microscissors (11 patients in group 2) to compare surgical feasibility and anatomic results with these instruments. The uterine cavity was distended by instillation of sorbitol and mannitol solution under manometric control. Two patients in group 1 and three in group 2 had a complete septum. In group 1, the mean operating time, plus or minus standard deviation (S.D.), was 22 +/- 6 minutes compared with 17 +/- 5 minutes in group 2 (p = 0.06). The mean amount of distension medium used, plus or minus S.D., was 890 +/- 153 milliliters in group 1 versus 671 +/- 170 milliliters in group 2 (p = 0.003). One woman in group 1 with complete uterine septum had a uterine perforation that was managed conservatively. Postoperative morbidity for the entire series was negligible. At follow-up ultrasonography and hysteroscopy performed two months postoperatively, a residual fundal notch > or = 1 centimeter deep was detected and corrected in four patients in group 1 and two in group 2. Our findings indicate that, in terms of operating time and efficacy, the resectoscope and microscissors are equally valid instruments to correct a septate uterus, with a feasibility rate of 100 percent. PMID- 8480266 TI - Evidence of venous stasis after abdominal insufflation for laparoscopic cholecystectomy. AB - Intraoperative venous stasis may increase the risk for perioperative deep vein thrombosis and pulmonary embolism. To determine if abdominal insufflation during laparoscopic cholecystectomy causes venous stasis, eight patients undergoing this procedure had their left common femoral veins examined by a duplex scanner before and after abdominal insufflation; the veins then were examined again before and after deflation. The right femoral veins were catheterized to measure femoral venous pressures. Abdominal insufflation to 14 millimeters of mercury pressure increased femoral venous pressures (10.2 +/- 4.1 millimeters of mercury to 18.2 +/- 5.1 millimeters of mercury; p < 0.001) and slowed peak blood velocities (24.9 +/- 8.5 centimeters per second to 18.5 +/- 4.5 centimeters per second; p < 0.05) without changing the cross-sectional areas (1.1 +/- 0.4 centimeter squared to 1.2 +/- 1.5 centimeter squared; p = NS) of the common femoral veins. Insufflation also reduced or eliminated pulsatility in the common femoral veins in 75 percent of the patients, indicating that insufflation was causing partial proximal venous obstruction. After 80 +/- 21 minutes of surgery, these changes remained significant. Deflation of the abdomen restored normal venous pulsatility in all patients, reduced femoral venous pressures (18.5 +/- 5.2 millimeters of mercury to 12.2 +/- 9.8 millimeters of mercury; p < 0.001), increased the peak blood velocities (14.2 +/- 6.8 centimeters per second to 28.1 +/- 16 centimeters per second; p < 0.05) and decreased the cross-sectional areas (1.4 +/- 0.6 centimeters squared to 0.9 +/- 0.4 centimeters squared; p < 0.05) of the common femoral veins, indicating venous decompression had occurred. The results suggest abdominal insufflation causes venous stasis during laparoscopic cholecystectomies. Measures shown to reduce intraoperative venous stasis, such as pneumatic compressive stockings, may benefit patients undergoing these procedures. PMID- 8480267 TI - Laparoscopic treatment of adnexal torsion. AB - Adnexal torsion remains an infrequent and difficult to diagnose gynecologic emergency. Until recently, laparoscopic diagnosis was followed by laparotomy. Now, with proper laparoscopic technique, it is possible to untwist the adnexa or to remove it with excellent results. We report herein our cumulative four year experience with laparoscopic detorsion or removal of the adnexa in 41 patients. Ten patients were simultaneously pregnant, seven having the ovarian hyperstimulation syndrome, six with paraovarian cysts and 18 with idiopathic torsion. All of the women had an uneventful recovery, with 14 of 19 patients who claimed desire for pregnancy becoming pregnant within one year after the procedure, emphasizing its advantages and safety. PMID- 8480268 TI - The use of oximetry in determining intestinal blood flow. AB - The intraoperative evaluation of intestinal ischemia and viability is often subjective and unreliable. The results of recent reports of pulse and surface oximetry have suggested that these techniques may be useful in assessing intestinal blood flow. In the current study, we evaluated and compared the ability of intestinal tissue oxygen saturation (as measured by pulse oximetry) and intestinal surface oxygen tension (as measured by surface oximetry) to determine the actual intestinal tissue blood flow (as measured with a radiolabeled microsphere technique). In five dogs, tissue oxygen saturation, surface oxygen tension and blood flow of the proximal and distal parts of the small intestine were measured under basal conditions. A clamp placed around the root of the superior mesenteric artery was then tightened to decrease the blood flow through this artery (as measured by an ultrasonic flow probe) by 50 percent and then by 75 percent, repeating all measurements after each reduction. The two consecutive reductions in superior mesenteric artery blood flow resulted in an average 54 and 76 percent reduction in tissue blood flow, respectively. As a result of these reductions in tissue blood flow, the average intestinal tissue oxygen saturation (percentage), as determined by pulse oximetry, decreased significantly from a basal value of 93 +/- 1 to 83 +/- 1 (p < 0.05) and then to 76 +/- 1 (p < 0.05) with the two progressive blood flow reductions. Intestinal surface oxygen tension decreased more steeply, from a basal value of 97 +/- 1 to 80 +/- 6 (p < 0.05) and then to 64 +/- 7 millimeters of mercury (p < 0.05) with the same two reductions in tissue blood flow. Both techniques were capable of estimating tissue blood flow, but pulse oximetry was quicker and simpler to use. We conclude that the pulse oximeter has the potential to be of value in the intraoperative assessment of intestinal blood flow. PMID- 8480269 TI - Burn induced cardiac dysfunction is reduced by pentoxifylline. AB - Thermal injury impairs cardiac contractility and slows isovolumic relaxation; these myocardial defects persist despite adequate fluid resuscitation. Results of previous studies suggest that myocardial dysfunction occurring after thermal injury results from the byproducts of activated neutrophils and other inflammatory mediators. Pentoxifylline (PTX) (Hoechst-Roussel Pharmaceuticals) has been shown to modulate many of the deleterious effects mediated by the neutrophil. In the current study, isolated coronary perfused hearts of rats were used to determine if PTX improved cardiac dysfunction after burn injury. Parameters measured included left ventricular pressure (LVP), maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max). Full thickness scald burns averaging 40 percent of total body surface area (burn groups, n = 22) or zero percent for sham burns (n = 10) were produced using a template device. Ten rats with burns were not fluid resuscitated and served as untreated burns. An additional 12 burned rats received PTX intraperitoneally (50 milligrams per kilogram) 30 minutes, six hours and 20 hours after thermal insult. The results of ex vivo studies confirmed significant burn mediated cardiac dysfunction as indicated by a decrease in LVP (55 +/- 4 millimeters of mercury, p < 0.001), +/- dP/dt max (1,063 +/- 119 millimeters of mercury per second; 874 +/- 82 millimeters of mercury per second, p < 0.001) and a downward shift of LV function curves from those obtained for sham-burn hearts. However, hearts from burned rats treated with PTX had significantly higher LVP (76 +/- 3 millimeters of mercury, p < 0.001) and +/- dP/dt max (1,790 +/- 54 millimeters of mercury per second; 1,334 +/- 50 millimeters of mercury per second, p < 0.001) compared with hearts from untreated burned rats and generated LV function curves comparable with those calculated for sham-burned rats. The current data indicate that PTX attenuates postburn cardiac dysfunction and suggest a potential role for the adjunctive use of PTX after thermal injury. PMID- 8480270 TI - Surgical treatment or gastric drainage only for intestinal obstruction in patients with carcinoma of the ovary or peritoneal carcinomatosis of other origin. AB - The records of 38 patients with advanced carcinoma of the ovary and 21 patients with peritoneal carcinomatosis of other origin who were treated for relief of intestinal obstruction were retrospectively analyzed. An explorative laparotomy was performed upon 40 instances, whereas in 25 instances, a large bore draining tube gastrostomy was done primarily. Retrospectively, the 40 explorative laparotomies were performed in two separate groups of patients. The first group consisted of 15 patients without palpable masses or ascites and five patients with intestinal obstruction as the first sign of ovarian disease. Another group of 20 patients presented with clinically manifest ascites or palpable masses, or both. The patients in group 1 survived for a median time of 154 days (range of 29 to 1,086 days) without recurrent intervention for obstruction. The patients in group 2 died after a median time of 36 days (three to 151 days). The explorative laparotomy was successful in only one patient in group 2. A third group of 25 patients was deemed inoperable and primarily received a tube gastrostomy. Twenty three patients presented with ascites or palpable masses, or both. They died after a median time of 33 days (eight to 163 days). Surgical therapy for relief of intestinal obstruction should only be considered in patients who do not present with manifest ascites or palpable masses and in patients with carcinoma of the ovary for whom effective chemotherapy is available. Percutaneous gastrostomy should be the method of choice for other patients. PMID- 8480271 TI - The failure of conventional methods to promote spontaneous transpyloric feeding tube passage and the safety of intragastric feeding in the critically ill ventilated patient. AB - Nasoenteral tube feedings are often recommended in critically ill patients when gastrointestinal tract function is intact. Conventional methods of placement include turning the patient on the right side and the use of drugs that stimulate peristalsis to promote transpyloric passage. A prospective study was initially performed to assess the success of conventional methods used to promote transpyloric feeding tube placement in patients requiring assisted ventilation admitted to the Surgical Intensive Care Unit (SICU) (Part I of the study). In 68 critically ill ventilated patients, placement of nasoduodenal feeding tubes was attempted. Successful transpyloric placement was achieved in only ten patients. There was no correlation between age, gender, admitting diagnosis, time of tube placement and successful placement. The second part of the study was initiated to assess the safety of nasogastric feeding in critically ill ventilated patients. Forty-two patients admitted to the SICU were considered candidates for gastrointestinal tract feeding and were fed through the gastric route. Twenty five patients reached enteral feeding goal rate within 72 hours, while 34 patients achieved goal rate by five days. Eight patients required total parenteral nutrition to meet nutritional needs because of an inability to achieve adequate nutritional support enterally. There were 11 complications noted in ten patients, including one episode of aspiration pneumonia. The presence of complications was not related to age, gender, admitting diagnosis, infusion method or type of formula used. Duodenal intubation using conventional methods in critically ill ventilated patients is unsuccessful in most patients. Nasogastric feeding in this group of patients can be safely administered in selected instances. PMID- 8480272 TI - A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. AB - Recent evidence of pancreatic penetration of several antibiotics active against the usual flora found in pancreatic sepsis, at therapeutic minimal inhibitory concentration, prompted the authors to perform a randomized, multicenter, clinical trial on imipenem prophylaxis in acute pancreatitis. Seventy-four patients with computed tomographic (CT) scans demonstrating necrotizing pancreatitis within 72 hours of onset were randomly assigned to two groups receiving no antibiotic treatment or 0.5 gram of prophylactic imipenem administered intravenously every eight hours for two weeks. Pancreatic sepsis was always detected by means of cultures (percutaneous CT or ultrasound-guided needle aspiration and intraoperative samples). The incidence of pancreatic sepsis was much less in treated patients (12.2 versus 30.3 percent, p < 0.01). Therefore, the authors recommend prophylactic use of imipenem in patients with acute necrotizing pancreatitis. PMID- 8480273 TI - A new approach to the treatment of nonsteroidal anti-inflammatory drugs induced gastric bleeding by free radical scavengers. AB - The effect of the free radical scavengers allopurinol (50 milligrams) and dimethyl sulfoxide (DMSO) (500 milligrams), taken orally four times a day, on the clinical outcome of hematemesis resulting from nonsteroidal anti-inflammatory drugs (NSAID) induced erosive gastritis was examined in a prospective randomized double-blinded controlled trial. In 180 fully evaluable patients with osteoarthritis or rheumatoid arthritis, administration of allopurinol (n = 63) or DMSO (n = 58) enabled significantly (p < 0.01) larger numbers of patients to remain hemodynamically stable with no rebleed relative to those in the control group (n = 59). The results of endoscopic examination 48 hours after admission demonstrated that gastric erosions were still present in significantly more patients in the control group (p < 0.01; n = 20; 50 percent) than in the allopurinol (n = 5; 9 percent) or DMSO (n = 4; 7 percent) groups. The radical scavengers also reduced the number of patients requiring blood transfusion because of a rebleed or continued bleeding and emergency operation relative to control values. It is, thus, construed that oxygen derived free radicals mediate the mechanism of NSAID induced erosive gastritis. Scavenging these radicals impairs the gastritis, stimulates healing and protects against the complications of its hemorrhagic episodes. PMID- 8480274 TI - Use of percutaneous stitches in laparoscopic mesh hernioplasty. AB - Sutures placed percutaneously have considerably facilitated the accurate intraperitoneal laparoscopic placement of synthetic mesh in the groin. The mesh effectively covers the abdominal wall defect, preventing further herniations in the area. PMID- 8480275 TI - End in end anastomosis to the diseased aorta. PMID- 8480276 TI - The usefulness of Avitene for the control of oozing in laparoscopic cholecystectomy. AB - An efficient method for the laparoscopic application of Avitene is presented herein. During laparoscopic operation, we cannot staunch bleeding points directly. Given such circumstances, the spray application of Avitene is a very effective method of hemostasis that should make laparoscopic operations even safer. PMID- 8480277 TI - The technique of giant prosthetic reinforcement of the visceral sac performed through an anterior groin incision. AB - The technique of giant prosthetic reinforcement of the visceral sac performed through an anterior groin incision is described. The procedure, which is usually performed through an abdominal incision, is indicated for all hernias of the groin that are at high risk for recurrence after classical repair and that are encountered unexpectedly during routine primary hernioplasty. PMID- 8480278 TI - The Whipples and their legacies in medicine. AB - George Whipple and Allen Whipple lived as contemporaries, but were not related. Their careers have many similarities. Both had the best available education and training. Both achieved distinction as administrator, educator and researcher. George Whipple founded the medical school at University of Rochester and was its first Dean for 32 years. Allen Whipple established a modern department of surgery at Columbia University and held the chair in surgery for 25 years. Both Whipples were published extensively and did extensive work on the gastrointestinal system. George Whipple's elucidation of the effect of liver on hemoglobin formation won for him a Nobel Prize. The work of Allen Whipple on the pancreas earned him the title of father of modern pancreatic surgical treatment. He also revitalized the surgical management of portal hypertension. Both Whipples were remembered with eponyms--George Whipple for his report on a small intestinal disease and Allen Whipple for his triad and operation. Both achieved international reputations and represented the finest embodiments of American medicine. PMID- 8480279 TI - Surgical treatment for tubal pregnancies. AB - From these data, it seems highly likely that conservation of the involved tube does not substantially increase the risk of a future ectopic pregnancy, although it does slightly increase the chance of a subsequent intrauterine pregnancy. This advantage of conservative therapy is also demonstrable in patients with a repeat tubal pregnancy. Pregnancy rates after conservative operation still compare favorably with those after in vitro fertilization. There seems to be a slightly increased risk of persistent trophoblastic activity after laparoscopic conservative therapy compared with conservative surgical treatment by laparotomy, but prospective randomized data are lacking. The psychosocial and economic benefits of laparoscopic treatment are well established. PMID- 8480280 TI - Electrophysiological characterization of rat striatal neurons in vitro following a unilateral lesion of dopamine cells. AB - The effects of a unilateral 6 to 19-week lesion of dopamine cells on the excitability of rat striatal neurons were investigated in vitro using the intracellularly recorded membrane properties of neurons obtained ipsilateral and contralateral to 6-hydroxydopamine (6-OHDA) injection sites. Neurons ipsilateral to the lesion site and in striatal tissue depleted of dopamine exhibited resting membrane potentials and membrane resistances similar to those recorded in contralateral striatal neurons. Denervation appeared to have no appreciable effect on the proportion of neurons exhibiting various patterns of neuronal spiking (repetitive, bursting, or single spike) evoked by depolarizing current pulses. Current-voltage determinations revealed nominal rectification in the majority of neurons and marked nonlinearity consistent with inward rectification at potentials hyperpolarized and depolarized to rest in a large proportion of the remaining neurons. Neurons ipsilateral to 6-OHDA lesion sites exhibited these relationships in the same proportion as contralateral control cells. However, ipsilateral neurons with nominal rectification exhibited an average rate constant for the early onset of small hyperpolarizing membrane transients which was significantly smaller than that of controls. This finding suggests that intrinsic membrane parameters regulating the excitability of certain striatal neurons may be under the influence of dopamine or other factors closely associated with nigrostriatal nerve terminals. PMID- 8480282 TI - [Development and changes in cardiology]. PMID- 8480281 TI - Striatal binding of the PET ligand 11C-raclopride is altered by drugs that modify synaptic dopamine levels. AB - Bilateral decreases in striatal 11C-raclopride binding were observed in adult female baboons with high resolution PET following administration of drugs that act centrally on dopaminergic neurons. At baseline and following administration of d-amphetamine (a dopamine-releasing drug), GBR-12909 (a potent dopamine reuptake inhibitor), or tetrabenazine (a biogenic amine depleting drug) PET scans of 11C-raclopride binding were obtained in a CTI 931 positron tomograph. In all studies, the ratio of the distribution volumes for the striatum to the cerebellum for 11C-raclopride binding decreased significantly by an average of 16.2% for d amphetamine, 22.1% for GBR-12909, and 28.3% for tetrabenazine while there were no significant changes observed in the cerebellum or in the rate of systemic metabolism of the radiotracer. These decreases exceed the test/retest variability of striatal 11C-raclopride binding measured in the same animals under identical experimental conditions (Dewey et al., 1992b). Together these studies demonstrate that PET measurements of striatal 11C-raclopride binding can be used to indirectly and non-invasively monitor changes in synaptic dopamine concentrations that result from a variety of neurophysiologic mechanisms. PMID- 8480283 TI - [What contributes to the occurrence of sexually transmitted diseases?]. PMID- 8480284 TI - [Prevalence of Chlamydia trachomatis in women applying for abortion in Oslo 1985 91]. AB - The prevalence of Chlamydia trachomatis was investigated in a retrospective study of 17,215 women who requested termination of pregnancy at Ulleval and Aker hospitals in Oslo during the years 1985-89 and 1991. The overall prevalence of C trachomatis decreased from 11.3% (267/2,354) in 1985 to 3.8% (112/2,958) in 1991. The reduction was considerable from 1985 to 1989 but only slight at the end of the period. The prevalence was higher in younger women during the whole period. In women < 25 years old the prevalence decreased from 16.7% in 1985 to 6.3% in 1991, and in women > or = 25 years old from 5.9% in 1985 to 1.8% in 1991. PMID- 8480285 TI - [Follow-up after treatment of genital chlamydia infection]. AB - We surveyed routine practice among a random sample of 302 Norwegian general practitioners. 49% perform a test of cure in all the patients whom they treat for genital infection caused by Chlamydia trachomatis. 22% of the practitioners test "most" patients, 19% test "some" patients while 10% of the general practitioners test none of the patients after treatment for genital chlamydial infection. Female practitioners perform more tests of cure than male practitioners do. Most tests are performed 1-4 weeks after completion of treatment. Although test of cure has been a controversial topic, we believe it to be a useful measure against the epidemic of genital chlamydial infections. The purposes of the test are to establish whether or not the treatment has been effective and ensure that the patient has not been reinfected by a partner who did not receive treatment. The test of cure must be performed later than two weeks after completion of treatment, in order to avoid false positive tests as a result of residual chlamydial antigen in the genitalia. PMID- 8480286 TI - [Endocrine treatment of prostatic cancer. A renaissance for parenteral estrogen]. AB - The standard treatment for advanced cases of cancer of the prostate is castration. Oestrogens, administered per os may have serious side effects, in particular thrombosis and cardiovascular complications. If the oestrogens are administered parenterally, changes in liver function can be avoided and risk of side effects markedly reduced. 38 patients have been treated at Huddinge Hospital in Stockholm, and 14 patients at Aker Hospital in Oslo, with polyoestradiol phosphate (Estradurin) 240 mg injected intramuscularly every 4th week (initial dose 320 mg). We can sum up our own experience as follows: Plasma testosterone is reduced to castration level after 2-3 weeks. Liver function, evaluated by the sexual hormone binding globulin level in plasma, remains unchanged. Morbidity and mortality from cancer are the same as may be achieved by surgical orchidectomy. The only side effect of significance is gynaecomastia. Follow-up of the patients does not indicate any increased risk of thrombosis or cardiovascular disease. The treatment is fairly cheap compared with other alternative methods of endocrine treatment. PMID- 8480287 TI - [Emergency admissions to a department of internal medicine. Are departments of internal medicine used optimally, and how would observation units affect the management of the department?]. AB - 279 consecutive emergency admissions to our Department of Internal Medicine were reviewed. Admission was appropriate for 58%. These patients consumed 88% of the "ward-days" during the period studied. Of the remaining patients, 22% could have been treated adequately in an observation unit, 10% need not have been hospitalized, and 10% should have been admitted to a different department. All stays in hospital lasting more than 50 days were due to lack of a place in a nursing home. If no patient had to wait more than 50 days, this would release 23% of the total "ward-day" capacity. The pressure on Departments of Internal Medicine could be reduced substantially by establishing observation units, and reducing the waiting time for a place in a nursing home. PMID- 8480288 TI - [The practical benefits of ambulatory continuous ECG recording]. AB - The diagnostic yield from ambulatory continuous ECG recording (Holter ECG) has been evaluated retrospectively in 200 consecutive patients referred from an urban population of 250,000 for arrhythmia diagnosis or evaluation. About half of the patients were in hospital, the other half were ambulatory. In 20/200 (10%) the examination was obviously useful: indication for therapy was documented or arrhythmia and symptoms did not coincide. 53/200 (26.5%) possibly benefited, with qualitative or quantitative observations of clinical interest, and 127 (63.5%) probably did not benefit (no previously unknown findings of importance). Of the 85 patients referred for syncope, six obviously benefited and ten possibly benefited from the examination. PMID- 8480289 TI - [Botulinum toxin. A new therapeutic alternative in spastic dysphonia (laryngeal abductor dystonia)]. AB - Laryngeal dystonia is a condition characterized by involuntary spasms of the laryngeal muscles. In most patients this involves the adductor laryngeal muscles (adductor laryngeal dystonia). Treatment with a variety of therapies, including speech therapy and pharmacotherapy, have led to minimal improvement. Injections of botulinum-toxin (Botox) bilaterally into the vocalis muscles is a new treatment for adductor laryngeal dystonia. Since May 1991 we have treated 23 patients with adductor laryngeal dystonia with botulinum-toxin. In 74% of the patients the voice improved within 24-72 hours, and effect lasted for 2-14 months (average four months). Most of the patients got a breathy voice and a mild sensation of dysphagia during the first week after the injection. PMID- 8480290 TI - ["Microscopic colitis" and collagenous colitis. Unusual explanation of diarrhea of unknown origin]. AB - The article describes two female patients with severe diarrhoea. Both patients were suspected of having an organic diarrhoea syndrome and underwent extensive investigations. No specific diagnoses such as inflammatory bowel disease, pancreatic cholera, malabsorption and surreptitous ingestion of laxatives could be established. Histologic examination of biopsy specimens from apparently normal colon revealed microscopic changes characteristic of "microscopic colitis" in one of the patients, and of collagenous colitis in the other. The authors discuss similarities between these two microscopic abnormalities in colonic mucosa and their close association with chronic watery diarrhoea. PMID- 8480291 TI - [Fatty tissue necrosis and oil granuloma after subcutaneous injections of vitamin B12]. AB - A patient is described who developed fatty tissue necrosis and oil granuloma in her thigh after repeated subcutaneous injection of vitamin B12. The injections were taken in a badly documented attempt to prevent migraine. The preparation used was vitamin B12 combined with a mineral oil to give slow release resorption. We describe the histopathological mechanism for reaction of fatty tissue to mineral oil injections. The 40 ml cavity of fat necrosis had to be drained out several times and over a long period of time before our patient was without symptoms. PMID- 8480292 TI - [Epilepsy and physical activity]. AB - Physicians should encourage epileptic patients to participate in sporting activities to enhance their physical fitness, self-esteem and social integration. Since about 5% of the population with epilepsy run the risk of suffering seizures induced by exercise, advice on such activity should be given individually. The physician should have good insight into the patient's medical history and should be interested in, and know about the different kinds of sport. The risk of injuries connected to seizure must be weighed against the physical, psychological and social problems which may result from exclusion from sports. PMID- 8480293 TI - [Infectious diseases and physical activity]. AB - Moderate physical activity has a beneficial effect on health. On the other hand, physical and psychological stress may have a suppressive effect on the immune system, implying that intense physical activity may possibly enhance the appearance of infectious diseases. There are no studies showing any effect on the immune system, nor on the frequency of infections, from physical training of low to moderate intensity. However, in several cases, high intensity training has been shown to produce chronic overtraining, which may impair general health. It is suggested that the extreme physical exertion of elite athletic training may suppress the immune system and thus lead to enhanced susceptibility to infectious diseases. Furthermore physical activity during the incubation period of several serious infectious diseases seems to be especially disadvantageous for the course of the disease. PMID- 8480294 TI - [Apolipoprotein E phenotyping--useful in the study of hyperlipoproteinemia type III]. AB - Apolipoprotein E (apo E) is a protein constituent of several plasma lipoproteins. Its major physiological role is to mediate the interaction of these lipoproteins and receptors. Three common apo E alleles and six phenotypes are known. The phenotype E2/E2 is associated with type III hyperlipoproteinemia. As a consequence of the increasing clinical interest in apo E phenotypes, especially in relation to the diagnosis of type III hyperlipoproteinemia, we have established a method for apo E phenotyping. Allele frequencies from a population of 211 healthy individuals are presented. The results show that, like as in Finland and Sweden the e4 allele is more frequent than in non-Nordic countries. PMID- 8480295 TI - [Closed functional treatment of fractures of the ulnar shaft]. AB - Various treatments of isolated fractures of the ulnar shaft have been attempted. The rates of non-union have varied widely, and impaired movement of the elbow and wrist is common at the end of the treatment. We present a series of eight patients who were treated initially with an above-elbow plaster, followed by a brace on the lower arm. All fractures healed with good functional results. PMID- 8480296 TI - [Chlamydia pneumoniae--pathogenesis and perspectives]. AB - Chlamydia pneumoniae, a Gram-negative bacterium, formerly named TWAR but identified as a distinct species since 1988, is now considered to be the most common agent of chlamydial infection in Scandinavia. C pneumoniae has a different tissue trophism from that of Chlamydia trachomatis, since C pneumoniae may infect bronchi and lungs, macrophages, monocytes, and endothelial cells. C pneumoniae, like other chlamydiae, has a slow, intracellular life cycle. An absence of reaction from the host cells, combined with scant tissual reaction owing to the low endotoxic activity of chlamydial lipopolysaccharide, may help to explain the usually discreet clinical picture. Atherosclerosis and coronary heart disease may follow chronic lung infection, and acute pneumonic episodes can trigger myocardial infarct. Asymptomatic infection with C pneumoniae is widespread. Intriguing diagnostic questions are the possible existence of a non-pathogenic carrier state, and the conceivable sensitization of the host with respect to a heterotypic, secondary chlamydial infection by, for example, C trachomatis, giving rise to an aggravated clinical picture. Early antibiotics are indicated to avoid the development of chronic disease. PMID- 8480297 TI - [Complaints about primary care physicians]. AB - The most serious complaints against general practitioners are investigated and dealt with by the Directorate of Health. A systematic review of 100 cases of complaint from 1983 up to 21 May 1992 showed that 57 of them concerned an urgent need of medical assistance and deputizing service. One-quarter of the complaints concerned telephone consultations. Incorrect diagnosis was the most frequent reason for the complaint. More than half of the cases referred to acute somatic diseases and accidents. The results will be used jointly by the Directorate of Health and the Norwegian Medical Association to improve practice. PMID- 8480299 TI - [Ethics and mathematics in clinical trials]. PMID- 8480298 TI - [Cancer anxiety in Somna--created by the newspaper Dagsrevyen?]. PMID- 8480300 TI - [Medical education--ready to fall down?]. PMID- 8480301 TI - [After the debate on death]. PMID- 8480302 TI - The role of acupuncture in analgesia. PMID- 8480303 TI - Practical management of dental hard tissue disorders in the dog. PMID- 8480304 TI - Perineal herniorrhaphy in the dog. PMID- 8480305 TI - Diagnosis and surgical modalities of megacolon in the cat. PMID- 8480306 TI - Surgical treatment of perianal fistulas in dogs, evaluation of 33 patients. PMID- 8480307 TI - Effect of slow release antibiotics on pin-tract infection. PMID- 8480308 TI - Arthritis--its classification, pathogenesis and clinical relevance. PMID- 8480309 TI - Understanding and controlling inherited diseases in dogs and cats. PMID- 8480310 TI - Polymorphic DNA markers for molecular diagnosis of inherited diseases in dogs. PMID- 8480311 TI - Adverse reactions to food [allergies]. PMID- 8480312 TI - Liposome-enhanced tumour therapy in canine mammary gland tumours. PMID- 8480313 TI - Canine growth hormone regulation: new insights. PMID- 8480314 TI - Clinical aspects and surgical procedures in trichiasis. PMID- 8480315 TI - Tumours of the lid margin, corneal ulcers and perforations. PMID- 8480316 TI - Diseases and basic surgery of the nictitating membrane. PMID- 8480317 TI - Diagnostic ultrasound in companion animals. PMID- 8480318 TI - Contrast radiography of the gastrointestinal tract: barium or air? PMID- 8480319 TI - Neoplasias and pseudoneoplasias. PMID- 8480320 TI - Congenital and genetic skin disease. PMID- 8480321 TI - Behaviour problems in cats. PMID- 8480322 TI - Recent advances in psychopharmacology. PMID- 8480324 TI - Anthropomorphism, spoiling, and environmental factors. PMID- 8480323 TI - Nonsteroidal anti-inflammatory drugs (NSAIDS) in companion animal medicine. PMID- 8480325 TI - Chemotherapy in reptiles. PMID- 8480326 TI - Hereditary Kooiker dog ataxia. PMID- 8480327 TI - Activity of mouse liver glutathione S-transferases toward trans,trans muconaldehyde and trans-4-hydroxy-2-nonenal. AB - This study investigated the catalytic activities of hepatic glutathione S transferase (GST) isoenzymes isolated from CD-1 mice toward two activated alkenals of toxicological relevance: trans,trans-muconaldehyde (MA), a putative myelotoxic metabolite of benzene, and trans-4-hydroxy-2-nonenal (HNE), a highly reactive lipid peroxidation product. The activity toward 1-chloro-2,4 dinitrobenzene (CDNB) was also determined. Four isoenzymes with pI values of 9.8, 8.7, 6.4, and 5.7 were each isolated from male and female mice. The isoenzymes with pI values of 8.7 and 6.4 are pi and mu class GSTs, respectively, whereas the pI 9.8 and 5.7 GSTs are both alpha class isoenzymes. CDNB activity was greatest in the pi (pI 8.7) isoenzyme of both sexes. In addition, the CDNB activity of the pi (pI 8.7) isoenzyme from males was markedly greater than the corresponding GST from female mouse liver. In contrast to CDNB, both MA and HNE were better substrates for the acidic alpha (pI 5.7) and mu (pI 6.4) GSTs, whereas minimal activity toward either alkenal was detected in the pi (pI 8.7) and alpha (pI 9.8) isoenzymes. Maximum activity toward MA and HNE was exhibited by the alpha (pI 5.7) isoenzyme of both sexes. The level of HNE activity observed with the alpha (pI 5.7) isoenzyme was five- to sixfold greater than that reported previously for any mouse GST isoenzyme. Moreover, the specific activities of the female alpha (pI 5.7) isoenzyme toward both HNE and MA were markedly greater than those of the corresponding isoenzyme from males. A similar gender-specific difference was noted in the activity of the mu (pI 6.4) isoenzyme toward HNE, but not toward MA. These results show that both MA and HNE are substrates for the alpha (pI 5.7) and mu (pI 6.4) GSTs of murine liver, with maximum activity toward both activated alkenals exhibited by the alpha (pI 5.7) isozyme. In addition, evidence is presented that demonstrates a female-dominant sex difference in the activity of the alpha (pI 5.7) isoenzyme toward MA and HNE, which contrasts sharply with the male-dominant activity of pi class GSTs toward CDNB. These results are consistent with the hypothesis that alpha and mu class GSTs are critical detoxication enzymes in female mouse liver, whereas pi-class GST isozymes predominate in the liver of male mice. PMID- 8480328 TI - The role of oxidative metabolism in hexachlorobenzene-induced porphyria and thyroid hormone homeostasis: a comparison with pentachlorobenzene in a 13-week feeding study. AB - Hexachlorobenzene (HCB) induces a broad spectrum of effects including disturbances in the heme synthesis (porphyria) and in thyroid hormone homeostasis. For most of its effects, biotransformation of the parent compound seems to be a prerequisite. The present study was designed to assess the relevance of the oxidative metabolites in HCB-induced toxicity, with special attention to the role of the reactive tetrachlorobenzoquinone (TCBQ). To this end, toxicity and biotransformation of HCB were compared with those of pentachlorobenzene (PCB), since this chemical is oxidized to the same products as HCB, i.e., pentachlorophenol (PCP) and TCBQ. Female Wistar rats received diets containing different dose levels of HCB or PCB for 13 weeks, with or without cotreatment with triacetyloleandomycin (TAO), a selective inhibitor of cytochrome P450IIIA1/2. Rats treated with HCB (high dose) had significantly elevated levels of urinary porphyrins from the 4th week on and had a significant hepatic accumulation of porphyrins at the end of the study. Both urinary porphyrin excretion and hepatic porphyrin accumulation were greatly inhibited in rats receiving cotreatment with HCB and TAO. However, the inhibition of HCB-induced porphyria by TAO cannot be explained by a diminished formation of the highly reactive TCBQ, since rats treated with a high dose of PCB, which had a several fold higher urinary excretion of PCP and TCHQ compared to a high dose of HCB, did not develop porphyria. Instead, the present study points to the involvement of a putative reactive intermediate in the primary oxidative step in HCB-induced porphyria, since based on paired observations of individual rats, the degree of porphyria was correlated to a high degree with excretion of PCP, whereas correlation of porphyria with early excretion of TCHQ was much weaker. This finding fits well with the fact that the mechanisms of oxidation of HCB to PCP and PCB to PCP are different. Both HCB and PCB were oxidized to PCP and tetrachlorohydroquinone (TCHQ), the reduced analog of TCBQ. Cytochrome P450IIIA1/2 appears to be involved in the conversion of HCB and PCB, since cotreatment of TAO resulted in a strongly diminished urinary excretion of PCP and TCHQ. Treatment with HCB as well as PCB results in disturbances of retinoid and thyroid hormone homeostasis. These effects, which have also been reported after exposure to polychlorinated biphenyls, originate from interference of hydroxylated metabolites (notably PCP) with the plasma thyroxine transport protein, transthyretine, and since this metabolite is formed from both HCB and PCB, this results in the same toxicity for both compounds. PMID- 8480329 TI - Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats. AB - In a previously conducted 2-year study, a concentration-dependent increase in Leydig cell adenomas was observed in Crl:CD BR(CD) rats fed diets containing the herbicide linuron. Linuron has been shown to be negative in a battery of six tests for genotoxicity; therefore, a nongenotoxic mechanism of tumorgenesis was investigated. Linuron is structurally related to the nonsteroidal antiandrogen, flutamide. Flutamide has also been shown to produce Leydig cell tumors within 1 year, presumably due to sustained hypersecretion of luteinizing hormone (LH) which occurs following disruption of the hypothalamic-pituitary-testicular (HPT) axis. To investigate whether linuron possesses antiandrogenic activity, sexually immature and mature CD rats were administered either 200 mg/kg linuron or 10 mg/kg flutamide (positive control) for 2 weeks. Accessory sex organs were weighed and serum hormone levels were measured to assess androgen status and alterations in the HPT axis. Serum from a multigeneration reproduction study with linuron was also analyzed for serum hormone levels. In addition, competitive receptor binding studies were conducted to evaluate the ability of linuron to bind to the androgen receptor. Linuron decreased accessory sex organ weights in sexually immature and mature linuron-treated rats. Increased serum estradiol and LH levels were observed in sexually mature linuron-treated rats. Serum estradiol and LH levels were also elevated in P1 and F1 male rats from the multigeneration reproduction study. These accessory sex organ and hormonal changes are consistent with those seen with the antiandrogen flutamide, the only exception being serum testosterone, which was elevated following exposure to flutamide but not to linuron. The inability of linuron to increase testosterone levels may reflect the lower potency of linuron as an antiandrogen compared with that of flutamide, which is a potent antiandrogen. Additionally, linuron competed with [3H]testosterone for binding to the androgen receptor. The IC50 data for competition to the androgen receptor suggest that linuron is approximately 3.5 times less potent than flutamide. These data are consistent with the effects seen with flutamide and demonstrate that linuron is a less potent antiandrogen than flutamide. Collectively, these data support the hypothesis that linuron produces Leydig cell tumors via an antiandrogenic mechanism where sustained hypersecretion of LH appears to be responsible for the development of Leydig cell hyperplasia and adenomas. PMID- 8480330 TI - Maturational changes in dermal absorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Fischer 344 rats. AB - An earlier study indicated that percutaneous absorption of a 40-nmol dose of TCDD decreased with aging in rats, suggesting that the potential for systemic exposure following dermal contact would be decreased in older age groups. In this study, maturational changes in potential for systemic exposure to TCDD following dermal application of a low dose (200 pmol) of this chemical were examined in male Fischer 344 rats. Absorption, tissue distribution, and elimination of TCDD, measured as TCDD-derived radioactivity, were examined 72 hr after dermal application of 200 pmol [3H]TCDD (111 pmol/cm2 applied over 1.8 cm2) to the interscapular region of 3-, 5-, 8-, 10-, and 36-week-old rats. The dose was applied in 60 microliters acetone and the application site was covered with a perforated metal cap; animals were held in individual metabolism cages. Dermal absorption was greatest in 3-week-old rats (approximately 129 pmol; approximately 64% of the administered dose), decreasing to approximately 80 pmol (approximately 40%) in 5-, 8-, and 10-week-old rats and to 45 pmol (approximately 22%) in 36 week-old rats. In each age group, 70 to 80% of the radioactivity remaining at the application site 72 hr after dosing could be removed with acetone swabs. Major tissue depots of radioactivity were liver and fat; skin and muscle were minor depots. Changes in distribution of absorbed TCDD-derived radioactivity reflected changes in body mass of these depots; however, tissue concentration also varied. Whole body dissection was performed on rats to determine body mass of tissue depots. Adipose tissue content (Y) increased linearly with body weight (X), Y = 0.03X + 2.1 (r2 = 0.95). Elimination of absorbed TCDD-derived radioactivity was incomplete in all age groups with larger residues being recovered in the carcass. Results indicate that TCDD is absorbed to a greater degree through skin of very young animals and that a significant decrease in potential for systemic exposure may occur during maturation and again during aging. PMID- 8480331 TI - In vitro analysis of the accumulation and toxicity of inorganic mercury in segments of the proximal tubule isolated from the rabbit kidney. AB - Cellular accumulation and toxicity of inorganic mercury were studied in suspensions (1 mg protein/ml buffer) of proximal tubular segments isolated from the kidneys of rabbits. Mercuric chloride containing trace amounts of radiolabeled inorganic mercury (203Hg2+) was added to the buffer to produce a concentration of inorganic mercury ranging from 0.1 to 10 microM. Significant release of lactate dehydrogenase (LDH) and significant decreases in oxygen consumption (QO2), which were used as indices of cellular injury, were detected only when the tubules were in the presence of 10 microM inorganic mercury. At this concentration of inorganic mercury, cellular release of LDH increased and QO2 decreased significantly between the 1st and 4th hr of exposure, by which time most of the proximal tubular cells were necrotic. Maximal cellular content of inorganic mercury was attained within the first 5 min of exposure, during which time nearly 70% of the inorganic mercury in the bath was removed. Accumulation of mercury was more gradual when the tubules were exposed to 0.1 microM inorganic mercury. Addition of 40 microM glutathione, cysteine, or bovine serum albumin to the bath provided the segments of the proximal tubule with complete protection from the toxic effects of 10 microM inorganic mercury. The rate of uptake of inorganic mercury was also significantly decreased. By the end of 4 hr of exposure only about 30% of the content of mercury in the bath was abstracted. These findings indicate that isolated segments of proximal tubules take up inorganic mercury very rapidly and subsequently become intoxicated. They also show that when compounds containing free sulfhydryl groups are in the presence of inorganic mercury in the bath, the rate of uptake of inorganic mercury is significantly decreased and the tubules are provided protection from the toxic effects of the inorganic mercury. PMID- 8480332 TI - Potentiation and antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin effects in a complex environmental mixture. AB - There is increasing need to understand the toxicity of complex environmental mixtures. The organic phase of a leachate (OPL) from the Love Canal chemical dump site is a complex mixture that contains over 100 organic compounds, including 0.74 ppm 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice congenic at the Ah locus were used to evaluate several toxic effects of the OPL, including immune function and hepatic enzyme induction. OPL toxicity was compared with that of pure TCDD in both C57BL/6J Ahb/b and congenic C57BL/6 Ahd/d (B6.D2) mice. Mice were given single oral doses of up to 2 g OPL/kg or 100 micrograms TCDD/kg, immunized, and evaluated after 7 days. The TCDD equivalent of the OPL was determined to be 3.9 and 5.0 ppm in C57BL/6J and B6.D2 mice, respectively. This is six times the TCDD content. The Ah phenotype-dependent response ratio was calculated by dividing the dose required to cause an effect in the B6.D2 strain by the dose causing the same effect in the C57BL/6J strain. Ratios based on both ED50s and the lowest observed adverse effect levels were used to determine whether each adverse effect was Ah phenotype-dependent, the extent to which TCDD contributed to the effect, whether there were interactive effects between the AhR ligands and nonligands and if they were additive, antagonistic, or synergistic, and whether the response was predictable based on the known chemical composition of the mixture. It was concluded that the non-TCDD component potentiated TCDD immune suppression, and possibly thymic atrophy, through AhR mechanisms. In contrast, this analysis indicated that the non-TCDD component of the OPL antagonized the ability of the TCDD component to induce hepatic AHH activity whereas OPL hepatomegaly was caused primarily by the non-TCDD component of the OPL. This study demonstrates that the toxicity of mixtures containing TCDD may not be accurately predicted based on the TCDD content alone and that this approach could be useful in the toxicologic assessment and management of environmental contamination. PMID- 8480333 TI - Acute inflammatory response to sheep red blood cell challenge in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): phenotypic and functional analysis of peritoneal exudate cells. AB - TCDD is a widespread environmental contaminant of concern to human health because of its well-recognized immunotoxicity in laboratory animals. Suppression of the murine antibody response to xenogeneic erythrocytes has been shown to be one of the most sensitive assays for TCDD immunotoxicity. However, the cellular mechanisms underlying the suppressed immune function have not been fully elucidated. In the present studies, peritoneal macrophage recruitment, activation, and antigen-presenting function in response to sheep red blood cell (SRBC) injection were compared in C57Bl/6 mice treated with a single oral dose of 0 or 5 micrograms TCDD/kg. In vehicle-treated mice, SRBC injection induced a typical inflammatory response in the peritoneal cavity. Within 6 hr, the number of neutrophils increased and remained elevated until 40 hr. Macrophage numbers increased at 24 hr and remained elevated through 72 hr. In TCDD-treated mice, a hyperinflammatory response to SRBC was observed. The total number of peritoneal exudate cells was significantly greater at 16, 24, and 40 hr after SRBC challenge when compared to that of vehicle-treated mice. The increased number of peritoneal cells reflected significant increases in both neutrophils and macrophages. Mac-1+ peritoneal cells were examined by two-color flow cytometric analysis on Days 0-3 after SRBC injection for expression of the activation markers F4/80 and I-A. The intensity of F4/80 fluorescence significantly decreased 24-72 hr following SRBC challenge, while fluorescence associated with I-A significantly increased at 72 hr. These changes are consistent with macrophage activation. TCDD did not significantly alter F4/80 expression on Mac-1+ cells, whereas I-A expression was increased earlier on cells from TCDD-treated mice. However, TCDD treatment did not alter the antigen presentation function of peritoneal cells, assessed by their ability to induce the proliferation of SRBC-primed T cells in vitro. The antigen-presenting function of adherent spleen cells was also not altered by TCDD exposure. To test the hypothesis that an excess number of phagocytes in TCDD treated mice were clearing the antigen more efficiently, leading to a smaller (e.g., suppressed) antibody response, we attempted to overcome TCDD suppression by increasing the amount of SRBC antigen used for challenge. However, the magnitude of the anti-SRBC response in TCDD-treated mice was not significantly altered by increasing the antigen challenge dose, suggesting that enhanced clearance of antigen by macrophage is not a mechanism for TCDD-induced suppression of the anti-SRBC response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8480334 TI - In vivo metabolism of chloroform in B6C3F1 mice determined by the method of gas uptake: the effects of body temperature on tissue partition coefficients and metabolism. AB - Mice exposed to various chemicals have been shown to respond by decreasing their core body temperature. To examine what effect such a response might have on the determination of in vivo metabolism, core body temperatures of B6C3F1 mice were recorded with temperature telemetry devices during exposure to chloroform (CHCl3) in a closed, recirculating chamber (100 to 5500 ppm). Significant decreases in body temperature occurred in all mice exposed to greater than 100 ppm CHCl3, with the greatest decrease of 14 degrees C occurring at 5500 ppm. A starting CHCl3 concentration of 4000 ppm had no effect on the 7-ethoxycoumarin O-deethylase (ECOD) activity or P450 levels determined at the end of a 5-hr gas uptake exposure. A physiologically based pharmacokinetic (PB-PK) model was developed to describe the effects of decreased body temperature on the analysis of metabolic data. In vitro ECOD activity as a measure of in vivo P450 metabolism was determined for temperatures ranging from 24 to 40 degrees C. In vitro enzyme activity decreased linearly from a maximum at 37 degrees C to one-third of this activity at 24 degrees C. A linear equation describing this enzymatic activity temperature correlation was incorporated into the PB-PK model structure to describe decreases in metabolic activity resulting from decreases in core body temperature. In vitro blood/air and tissue/air partition coefficients were determined for CHCl3 at temperatures ranging from 24 to 40 degrees C. All blood/air and tissue/air partitions increased with decreasing temperature, while the tissue/blood partition coefficients calculated from the tissue/air and blood/air partitions decreased with decreasing temperature. Adding these temperature corrections to the model greatly improved the overall fit of the gas uptake curves at all concentrations. Incorporation of a first-order metabolic rate constant was also required to provide an adequate representation of the data at high concentrations. The analysis of gas uptake data by the use of a PB-PK computer model is a very powerful technique for determining in vivo metabolism of many volatile compounds, but the incorporation of significant deviations from a generally used model structure (i.e., Ramsey-Andersen model) to account for shortcomings of the model's ability to adequately analyze a gas uptake data set should be based on data collection when possible. PMID- 8480335 TI - Ovariectomy enhances cadmium-induced nephrotoxicity and hepatotoxicity in rats. AB - The toxicity of cadmium (Cd) chloride was studied in ovariectomized (OX) female rats and non-OX female rats after intravenous administration of the compound at doses of 2.0 and 3.0 mg/kg for 14 days. Mild hypochromic microcytic anemia developed in all rats treated with Cd, but growth retardation in the OX rats was more prominent than that in the non-OX rats. There was an increase of AST and ALT and a decrease of total cholesterol and the A/G ratio in both OX and non-OX rats treated with Cd. The hepatic and renal Cd concentrations increased in a dose dependent manner, and the concentrations in both organs on Day 14 were comparable in the 3.0 mg/kg OX group (liver, 270.0 +/- 39.6 micrograms/g; kidney, 121.3 +/- 10.1 micrograms/g) and non-OX group (liver, 277.0 +/- 29.9 micrograms/g; kidney, 100.8 +/- 1.3 micrograms/g). Hepatocyte necrosis developed only in OX rats treated with Cd, and the nephrotoxicity of Cd was also notably enhanced by ovariectomy, since Cd nephropathy affected the proximal convoluted epithelium more severely and more frequently in OX rats than in non-OX rats. BrdU-labeled cells in the renal cortex were increased by approximately 2.7-fold in OX rat (7.4 cells/mm2) over those in the renal cortex in non-OX rat (2.7 cells/mm2). In conclusion, the present study demonstrated that ovariectomy enhanced Cd-induced nephrotoxicity and hepatotoxicity in rats. PMID- 8480336 TI - The involvement of Kupffer cells in carbon tetrachloride toxicity. AB - Carbon tetrachloride (CCl4) is a classical pericentral hepatotoxicant; however, precise details of its mechanism of action remain unknown. One possibility is that Kupffer cells participant in this mechanism since CCl4 elevates calcium, and the release of toxic eicosanoids and cytokines by Kupffer cells is calcium dependent. Therefore, these studies were designed to evaluate the role of Kupffer cells in CCl4 toxicity in the rat in vivo. Kupffer cells were destroyed selectively with gadolinium chloride treatment (10 mg/kg GdCl3 iv) 1 day prior to administration of CCl4 (4 g/kg ig). Twenty-four hours after CCl4 treatment, rats were anesthetized, blood samples were drawn for aspartate aminotransferase (AST) determination, which is indicative of parenchymal cell damage, and trypan blue was infused into the liver to stain the nuclei of dead hepatocytes. AST levels were in the normal range and trypan blue staining was negligible in livers from vehicle- or GdCl3-treated rats. As expected, CCl4 treatment alone elevated AST levels to values over 4000 U/liter and caused massive cell death (60-90 trypan blue-positive cells/pericentral field). In dramatic contrast, the elevation in AST and cell death due to CCl4 were almost completely prevented by GdCl3 treatment. In attempts to understand this phenomenon, metabolic and detoxification pathways were assessed. CCl4 is metabolized via cytochrome P450 II.E.1; however, GdCl3 treatment did not alter this pathway as assessed from p nitrocatechol formation from the selective substrate, p-nitrophenol. GdCl3 treatment also had no effect on hepatic glutathione levels. On the other hand, GdCl3 treatment significantly reduced infiltration of neutrophils resulting from exposure to CCl4. These data clearly support the hypothesis that Kupffer cells participate in the mechanism of toxicity of CCl4 in vivo, possibly by release of chemoattractants for neutrophils. PMID- 8480337 TI - Characterization of vitamin A potentiation of carbon tetrachloride-induced liver injury. AB - Pretreatment of rats with large doses of vitamin A (VA, retinol) has been shown to potentiate carbon tetrachloride hepatotoxicity. The relationship between VA dose or pretreatment duration with VA and the extent of potentiation of CCl4 hepatotoxicity is unknown. Therefore, VA was administered to male SD rats (180 200 g) by oral gavage in daily doses of 100,000, 150,000, 200,000, or 250,000 IU/kg for 3 weeks. In another experiment, rats were given VA in a daily dose of 250,000 IU/kg for 1 day, 1, 2, 3, or 5 weeks. At 24 hr after the last VA dose, CCl4 (0.15 ml/kg, ip) was administered. Hepatotoxicity was assessed by increases in plasma alanine aminotransferase activity and by histological evaluation of the liver. Additionally, the correlation between the hepatic concentration of retinol and retinyl palmitate after VA treatment and the extent of potentiation of CCl4 induced liver injury was studied. In the initial 3-week dose-response study, as the daily dose of VA increased so did the degree of potentiation of CCl4 hepatotoxicity. All treatment durations with VA (250,000 IU/kg per day), except 1 day, resulted in equivalent potentiation of CCl4 hepatotoxicity. VA treatment did not result in elevated hepatic concentration of retinol. However, VA treatment did increase the concentration of retinyl palmitate in the liver (except for the 1-day treatment). No linear correlation could be seen between the hepatic concentration of retinyl palmitate and the extent of VA potentiation of CCl4 hepatotoxicity. VA treatment also potentiated to hepatotoxicity of minimally hepatotoxic doses of acetaminophen, allyl alcohol, and endotoxin. Because these chemicals produce hepatic injury by diverse mechanisms it is concluded that VA potentiates hepatic injury by altering a process involved in the progression of cell injury. PMID- 8480338 TI - Vitamin A potentiation of carbon tetrachloride hepatotoxicity: enhanced lipid peroxidation without enhanced biotransformation. AB - To better understand the mechanism by which vitamin A (VA, retinol) potentiates the hepatotoxicity of carbon tetrachloride, its effect on metabolism and covalent binding of CCl4 as well as its effect on lipid peroxidation was determined. 14CCl4 (0.15 ml/kg, 21.4 microCi/mmol) was administered to male SD rats that had been treated with vitamin A (250,000 IU/kg/day for 1 week) or vehicle. Vitamin A pretreatment did not increase the 24-hr biotransformation of 14CCl4 to 14CO2, to exhaled volatile organics, or to metabolites excreted in the urine or feces. Furthermore, there was no dramatic effect of vitamin A pretreatment on the covalent binding of 14CCl4 equivalents to hepatic lipids and proteins at early time points (1/2-4 hr) after administration of 14CCl4. The microsomal concentration of cytochrome P450 was unchanged by vitamin A treatment. There was a dramatic increase (6-8x) in the amount of ethane exhaled in those rats treated with vitamin A and then administered CCl4 compared to that of those administered CCl4 without pretreatment. The enhanced lipid peroxidation as evidenced by the increased exhalation of ethane was not the result of vitamin A-induced decreases in hepatic glutathione or vitamin E. These data indicate that the potentiation of CCl4 hepatotoxicity by vitamin A pretreatment is associated with an enhancement of lipid peroxidation that is independent of changes in CCl4 biotransformation or the hepatic concentration of two important hepatoprotective agents. PMID- 8480339 TI - Vitamin A potentiation of carbon tetrachloride hepatotoxicity: role of liver macrophages and active oxygen species. AB - Pretreatment of rats with large doses of vitamin A (VA) potentiates the hepatotoxicity of CCl4. Because our previous studies indicate that VA treatment does not enhance CCl4 metabolism but does enhance CCl4-induced lipid peroxidation and activates liver Kupffer cells to release increased amounts of oxygen-centered free radicals, the current studies were designed to determine if VA treatment potentiates CCl4-induced liver injury through increased release of reactive oxygen species. Plasma clearance of colloidal carbon, an index of Kupffer cell phagocytic activity, was enhanced two- to threefold in rats treated for 7 days with VA (retinol, 250,000 IU/kg per day). Accordingly, VA treatment alone caused Kupffer cell activation. To determine if these activated Kupffer cells could potentiate hepatic injury through release of reactive oxygen species upon CCl4 challenge, polyethylene glycol coupled-superoxide dismutase (PEG-SOD, 10,000 IU/kg) or -catalase (PEG-CAT, 40,000 IU/kg) was given iv 2 hr after CCl4 (0.15 ml/kg, ip) to control or VA-pretreated rats to quench any released reactive oxygen. PEG-SOD and PEG-CAT effectively blocked VA potentiation of CCl4 liver injury as assessed at 24 hr by change in plasma ALT. Methylpalmitate (MP, 2 g/kg), an inhibitor of Kupffer cell phagocytosis and related oxygen burst, also blocked the potentiation of liver injury when given iv 24 hr before CCl4 to VA pretreated rats. At the doses used, PEG-SOD or PEG-CAT did not influence CCl4 toxicity in control rats (at 0.15 or 2 ml CCl4/kg). Importantly, SOD, CAT, and MP blocked the enhanced lipid peroxidation induced by CCl4 in VA-pretreated rats. From these findings we conclude that the potentiation of CCl4 liver injury by VA pretreatment is mediated, at least in part, by active oxygen species released from Kupffer cells and possibly other macrophages that are activated by VA. Supporting this conclusion is the failure of VA pretreatment to increase the release of LDH from suspension of hepatocytes incubated with CCl4. PMID- 8480340 TI - Differential ovotoxicity of 4-vinylcyclohexene and its analog, 4 phenylcyclohexene. AB - Vinylcyclohexene (VCH) is an industrial byproduct that is known to cause the destruction of ovarian follicles in mice. Its analog, 4-phenylcyclohexene (4PC), is a volatile product from latex-backed carpeting. These studies were undertaken to assess the structure-activity relationships of these compounds and the potential for 4PC to cause ovotoxicity. Female B6C3F1 mice were dosed with VCH (6 mmol/kg/day, ip) or 4PC (3 or 6 mmol/kg/day, ip) daily for 30 days. Treatment with VCH caused dramatic reductions in small and growing follicles as compared to those of vehicle controls. No treatment-related ovarian lesions were associated with 4PC administration. Plasma FSH concentrations were unaltered by treatment with either compound. These results indicate that in mice, the substitution of the phenyl for the vinyl group in the 4 position eliminates the ovotoxicity caused by this class of compounds. Presumably, the ability of the vinyl group to form an epoxide (or dihydrodiol) and/or its smaller size accounts for this difference in ovarian toxicity. PMID- 8480341 TI - Ozone inhalation stimulates expression of a neutrophil chemotactic protein, macrophage inflammatory protein 2. AB - Short-term exposure of humans and animals to ozone results in increased lung neutrophils; however, the mechanisms underlying this response are not completely understood. We examined the potential involvement of the neutrophil chemotactic factor, macrophage inflammatory protein 2 (MIP-2), in ozone-induced inflammation. Exposure-response relationships for ozone and MIP-2 expression were characterized by exposing C57B1/6 mice to 0.1-2 ppm ozone for 3 hr and determining lung levels of MIP-2 mRNA 6 hr after exposure. Temporal relationships between ozone and MIP-2 were determined by exposing mice (2 ppm ozone x 3 hr) and characterizing MIP-2 mRNA expression 0, 2, 6, and 24 hr after exposure. Neutrophils in lung lavage fluid were determined in both exposure-response and time course studies. Ozone concentrations > or = 1.0 ppm increased MIP-2 mRNA and this increase corresponded with recruitment of neutrophils. MIP-2 mRNA was increased immediately after ozone exposure and decreased to control levels by 24 hr. To examine the role of direct oxidant effects in ozone-induced MIP-2 expression, alveolar macrophages were exposed in vitro for 4 hr to 10(-10)-10(-5) M hydrogen peroxide and MIP-2 expression was characterized. MIP-2 mRNA levels in lung macrophages were increased by > or = 10(-9) M hydrogen peroxide. In summary, our findings suggest the chemotactic protein MIP-2 may be responsible, at least in part, for ozone induced increases in lung neutrophils and indicate that direct exposure of alveolar macrophages to an oxidant is sufficient to induce MIP-2 expression. PMID- 8480342 TI - Thymectomy as treatment of autoimmune diseases other than myasthenia gravis. AB - This paper reviews the different series of thymectomies performed in patients with autoimmune diseases other than myasthenia gravis. It is possible that thymectomy can decrease the activity of T-helper lymphocytes or, alternatively, it may enhance the activity of T-suppressor lymphocytes, whose function is depressed in autoimmune diseases. Thymectomy was performed empirically for systemic lupus erythematosus and rheumatoid arthritis. The therapeutic benefits were questionable. Conflicting results were reported for thymectomy against autoimmune hemolytic anemia. Several trials were conducted to assess the therapeutic value of thymectomy in multiple sclerosis. Benefits were achieved only in relapsing-remitting but not in chronic-progressive multiple sclerosis. The effect of thymectomy in autoimmune diseases associated with myasthenia gravis were also reported. The authors conclude that thymectomy as treatment for autoimmune diseases other than myasthenia gravis is not elective therapeutic choice and it is acceptable only in selected cases. PMID- 8480343 TI - Effect of ambient temperature on immune functions of athymic nude mice. AB - We performed cytoflourometric analysis of the expression of various T and B surface markers on lymphocytes isolated from bone marrow, spleen and lymph nodes of nu/nu and +/+ mice kept at 22 or 28 degrees C for various time intervals. In bone marrow of nu/nu mice the cold exposure decreased the expression of sIg and CD4 molecules and increased expression of MHC class II antigens. In the spleen, the numbers of MHC class II and sIg expressing lymphocytes continually decreased with the length of cold exposure. At the same time, the number of CD4+ cells increased. The most pronounced changes in lymph nodes were observed in the expression of CD5 antigen. The values obtained from euthymic mice kept at cold temperature were always comparable to those found in mice kept at 28 degrees C. Exposure to lowered temperature caused in nu/nu mice also significant changes in appearance of subpopulations of cells differing in size and in density of antigens. The changes did not affect the antibody response to a thymus independent antigen. PMID- 8480344 TI - Phenotype and adhesion characteristics of rat thymic macrophages cultivated in serum-free medium. AB - Rat thymic macrophages (TMF) were cultivated in serum-free medium (Biorich 2) using an explant technique. This medium favored the growth of macrophages and inhibited the proliferation of other non-lymphoid cells. Macrophage characteristics of cultivated cells were confirmed by their morphology, NSE activity and positivity (approx. 95%) with ED1 and Mar 1 mAbs (pan-macrophage markers in the rat). The majority of non-adherent cells (NAC) released in culture medium during the proliferation of TMF also possessed macrophage characteristics. Both adherent TMF and NAC were heterogeneous cells expressing cortical/CMZ phenotype (ED2+, R-MC 41+, R-MC 42+) and CMZ/medullary phenotype (R-MC 43+, R-MC 44+). NAC population contained higher proportion of cells expressing class II MHC molecules, IL-2R and 1F119 antigen compared to adherent TMF. The TMF phenotype changed during cultivation and upon stimulation with inflammatory cytokines (IL 1, IFN-gamma, TNF-alpha). TMF formed rosettes with syngeneic or allogeneic thymocytes both at 37 and 4 degrees C. The percentages of rosettes was dependent on the incubation time and TMF/thymocyte ratio. A higher percentage of immature thymocytes (CD4-CD8- or CD4+CD8+) bound to TMF compared to mature, cortisone resistant thymocytes. The involvement of TMF membrane molecules in TMF/thymocyte adhesion was tested by preincubation of TMF with specific mAbs. It was found that Mar 1 mAb was partially inhibitory, OX-42 (anti CD11b) was slightly stimulatory, whereas other mAbs had no significant effect. PMID- 8480345 TI - Transfusion science and practice in developing countries: "...a high frequency of empty shelves....". PMID- 8480346 TI - Artificial preservatives for platelets. PMID- 8480347 TI - Posttransfusion survival of stored red cells and membrane-associated complement inhibitors. PMID- 8480349 TI - Storage of platelets in additive solutions: the effect of citrate and acetate in in vitro studies. AB - The in vitro effects of storage of platelets prepared from 6 pooled buffy coat units and stored in a platelet storage medium consisting of CPD and plasma and different platelet additive solutions were evaluated. The total count of platelets per pooled unit included in the present investigation (n = 20) was 335 +/- 35 x 10(9) (mean +/- SD). Measurements of pH, pO2, pCO2, glucose, lactate, ATP, total adenine nucleotide content, and extracellular adenylate kinase activity were performed in a three-part study. The observations were 1) During storage in saline and citrate (10 mmol/L of citrate), the consumption of glucose and the production of lactate were significantly increased over the values with storage in saline, which were used as a reference. The values for pH at Day 6 were significantly lower. 2) The effects of different concentrations (10, 20, and 30 mmol/L) of acetate in saline were studied. With the exception of significantly higher pH values in saline and acetate, no significant differences were seen in the effects with saline and those with saline and acetate. 3) The combined effect of citrate and acetate was evaluated. The consumption of glucose and the production of lactate, the values for pO2, and extracellular adenylate kinase activity were significantly lower with saline and citrate and acetate than with saline and citrate. Significantly higher values for pH were found at Day 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480348 TI - Lack of clinical significance of "enzyme-only" red cell alloantibodies. AB - In a retrospective study on samples from 10,000 recently transfused patients, 35 samples were found to contain an antibody that reacted with ficin-treated red cells but was not demonstrable by low-ionic-strength saline solution and indirect antiglobulin test (LISS-IAT). In those 35 patients, the specificity of the antibody was such that each patient would have been transfused with antigen negative blood had the antibody reacted in LISS-IAT. Tests on red cells from the units already transfused showed that 19 patients had among them received, by chance, 32 antigen-positive and 74 antigen-negative units. The remaining 16 patients had among them received 57 units that were, again by chance, all antigen negative. One patient given antigen-positive blood suffered a delayed transfusion reaction; in two others the antibodies became LISS-IAT active after transfusion. However, similar changes to the LISS-IAT-active state were seen with two antibodies of patients given only antigen-negative blood. Also found in the 10,000 patients were 28 clinically insignificant antibodies, 77 sera in which the antibody was too weak to identify, and 216 autoantibodies that reacted only with ficin-treated red cells. These data support a belief, generally held in the United States but not necessarily elsewhere, that the use of protease-treated red cells for routine pretransfusion tests creates far more work than the accrued benefits justify. PMID- 8480350 TI - Roles of acetate and phosphate in the successful storage of platelet concentrates prepared with an acetate-containing additive solution. AB - The development of a synthetic medium for platelet storage is an important goal in transfusion medicine. Its use would make large volumes of plasma available for fractionation and might improve the quality of platelets after storage. Several investigators have described successful storage in media containing acetate. The previous work of the authors showed that platelet concentrates (PCs) can be stored successfully for 5 days at 22 degrees C by using an additive solution (Seto sol) to replace 80 to 95 percent of the plasma usually employed as a suspending medium. Seto sol contains 23 mM (23 mmol/L) sodium acetate and 25 mM (25 mmol/L) sodium phosphate. The roles of acetate and phosphate in achieving successful platelet storage were studied in the work reported here. The concentration of acetate decreased linearly for 7 days at 0.61 +/- 0.11 mumol per day per 10(9) platelets in parallel with the disappearance of 1-14C or 2-14C acetate. There was no disappearance of tritiated acetate from PCs or of 1-14C acetate from platelet-free mixtures of plasma and Seto sol, which suggests that the disappearance of 14C acetate from PCs reflected oxidation to CO2, which could leave PCs through the walls of the plastic container. Since O2 consumption was 1.47 mumol per day per 10(9) platelets, and the oxidation of a molecule of acetate requires 2 molecules of oxygen, acetate oxidation accounted for approximately 85 percent of oxygen consumption by platelets. The pH of PCs stored in Seto sol was nearly constant for 7 days, whereas, without acetate, it fell to 6.4 +/- 0.1 on Day 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480351 TI - Storage of single-donor platelet concentrates: metabolic and functional changes. AB - During the last decade, the trend toward intensifying chemotherapeutic regimens in patients with hematologic malignancies rapidly increased the demand for single donor platelet concentrates (PCs). The logistics of such supply, however, necessitated the storage of these blood components prior to transfusion. Today, most blood centers use di(2-ethylhexyl)phthalate-free blood bags, which are assumed to allow a storage period of up to 5 days. This report describes biochemical and functional changes of stored single-donor PCs, which may influence the expected quality of PCs. The acid-base status is characterized by an initial respiratory alkalosis compensated by a metabolic acidosis. Changes in extracellular electrolyte, lactate dehydrogenase, glucose, lactate, elastase, and complement levels, as well as in the release of alpha granule content and the initial activation of plasma coagulation, are demonstrated. These changes result in a functional impairment of stored PCs as reflected by thromboxane and serotonin release reaction and by aggregation and in vitro bleeding time studies. In contrast, in vivo recovery and survival rates have been reported to be unaffected. Whether the good recovery and survival rates are caused by a rejuvenescence of stored PCs in vivo or are due to injured circulating platelets has not yet been proven. PMID- 8480352 TI - Refrigerated storage of lyophilized and rehydrated, lyophilized human red cells. AB - Human red cells (RBCs) were collected in CPDA-1 and then freeze-dried in lyoprotective solution. The lyophilized RBCs were then stored at -20 degrees C for 7 days. At the end of the storage period, the lyophilized RBCs were rehydrated and washed in dextrose saline. The washed, reconstituted, lyophilized RBCs were resuspended in final wash solutions of ADSOL, CPDA-1, or a special additive solution containing glucose, citrate, phosphate, adenine, and mannitol, and then they were stored at 4 degrees C for an additional 7 days. The main purpose of this study was to determine whether human RBCs can be lyophilized in such a manner that normal metabolic, rheologic, and cellular properties are maintained during rehydration and subsequent storage in standard blood bank preservative solutions. Our results show that reconstituted, lyophilized RBCs maintained levels of ATP, 2,3 DPG, lactate, and cellular properties that are equal to or better than those in control nonlyophilized RBCs stored for a comparable period in CPDA-1. Reconstituted, lyophilized RBCs stored at 4 degrees C after rehydration also show better maintenance of ATP, 2,3 DPG, and lactate than do control RBCs stored in the same preservative solutions for comparable periods. PMID- 8480353 TI - Blood donation and patterns of use in southeastern Nigeria. AB - A retrospective study of donor blood availability and patterns of use from 1984 through 1988 was conducted in a 400-bed university teaching hospital in Nigeria by extraction of data from the master registers for blood donors and recipients. Blood transfusion requests, number of persons who underwent phlebotomy, number of crossmatches performed, and blood use increased each year during the period of study. Average wastage rate and crossmatch-to-transfusion ratio were 3.5 percent and 1.61, respectively. Replacement blood donation constituted 98 percent of available donor blood. Obstetrics and gynecology and surgery patients used 70.4 percent of the donor blood. The donor blood units were used as whole blood (81%) because of a lack of infrastructure such as a refrigerated centrifuge. Less than 5 percent of the donors were females. It is concluded that the levels of voluntary blood donation and general blood supply are unacceptably low. The need for a functional National Blood Transfusion Service is highlighted. PMID- 8480354 TI - Blood donation behavior of Hispanics in the lower Rio Grande Valley. AB - This study was designed to determine the blood donation behavior and attitudes of Hispanic residents of the Lower Rio Grande Valley for the purpose of developing promotional and educational approaches to enhance levels of donor participation. Personal interviews of 545 respondents were conducted in English and Spanish using quota sampling and standard intercept techniques at lower- and middle income supermarkets in five cities during a payday weekend. A number of research hypotheses were established to test for demographic, behavioral, and attitudinal differences that were observed in donors and nondonors using chi-square analysis and multiple discriminant analysis. After analyzing the difference between Hispanics and non-Hispanics for blood donation rates, all non-Hispanics were eliminated from analysis, and the remaining 419 Hispanics were evaluated on the basis of their donor behavior. Donation among Hispanics was most likely to be by better-educated, English-speaking, higher-job-status individuals who had participated in a blood donation drive. Donors tend to have parent(s) who were donors, and they were also more likely to carry an organ donor card. Donors were found to vary in their behaviors as well as their attitudes and beliefs. Perceptions of a lack of safety in donating, the risk of contracting acquired immune deficiency syndrome, and the financial motivation of donors were most pronounced among Hispanics, which indicated a need for improved education on these issues. PMID- 8480355 TI - Safety and efficacy of preoperative donation of blood for autologous use by patients with end-stage heart or lung disease who are awaiting organ transplantation. AB - Many patients are, perhaps inappropriately, denied the benefits of autologous blood transfusion, because they are thought to be too ill to donate blood safely. The safety and efficacy of autologous blood donation by selected patients with end-stage heart or lung disease who are awaiting organ transplantation were studied to determine if even these critically ill patients could be suitable candidates for autologous blood donation. Seventy-two adults awaiting heart or lung transplantation were evaluated for autologous blood donation in a hospital based blood collection facility. Phlebotomy was performed if the patient met the required medical eligibility protocol, and if he or she consented to participate. Units of blood were separated into packed red cells and plasma and stored in a frozen state. Of 48 heart transplant candidates, 31 (65%) were each able to donate 1 to 8 units of blood. The median number of exposures to allogeneic components was 1 for patients who donated and 7 for nondonors (p = 0.0141). Among patients who donated, 54 percent required allogeneic components, as compared to 88 percent of nondonors (p = 0.0968). Of 24 lung transplant candidates, 15 (63%) made 1 to 6 donations each. The median number of exposures to allogeneic components was 0 for donors and 2 for nondonors (p = 0.1871), but only 45 percent of donors required allogeneic components, as compared to 100 percent of nondonors (p = 0.0418). No serious complications during or following phlebotomy were observed. It is concluded that autologous blood donation by patients with end stage heart or lung disease may be safe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480356 TI - Transfusion therapy: improved patient care and resource utilization. AB - Improving the quality of medical care while reducing costs is one of the major challenges facing the health care system in the United States. At a 1020-bed, tertiary-care, teaching hospital, the Transfusion Committee modified transfusion practice by establishing new transfusion guidelines based upon national standards rather than local practices and by implementing educational and monitoring systems. Over a 3-year period, the number of transfusions decreased, the types of transfused components changed, and the waste due to unused components decreased. From the baseline of Fiscal Year (FY) 1989 (89), the number of exposures to components from allogeneic blood donors for the patient population decreased by 11,015 in FY 90, 14,067 in FY 91, and 16,990 in FY 92, thereby decreasing the risk of transfusion-transmitted disease, transfusion reaction, and alloimmunization. As compared to costs in FY 89, the altered transfusion practices resulted in cost savings of $376,269 in FY 90, $566,375 in FY 91, and $684,704 in FY 92. Over the 3-year period, exposures to components from allogeneic blood donors for the patient population were reduced by 42,072, and the total cost savings was $1,627,348. The methodology and results should be reproducible at other hospitals. PMID- 8480357 TI - Rh phenotypes of Chinese blood donors in Hong Kong, with special reference to weak D antigens. AB - Among Hong Kong Chinese blood donors, 99.71 percent were found to be D+. Of these, 55.02 percent were of the phenotype CCDee. The Du phenotype was found to be present in 0.016 percent. Among the 0.27 percent who were apparently D-, 0.079 percent were of the Del phenotype, while the remaining 0.19 percent were "true D ," as defined by a nonreactive eluate obtained by an adsorption and elution procedure using anti-D. The ccdee phenotype constitutes 56.77 percent of the "apparent D-" and 80.24 percent of the true D-. Data show that anti-D rarely occurs in Hong Kong Chinese, and it is postulated that this could be due to the presence of a very weak form of the D antigen among many of those who appear to be D-. PMID- 8480359 TI - Correction of the corrected count increment units. PMID- 8480358 TI - Selection of white cell-reduced blood components for transfusions during early infancy. PMID- 8480360 TI - Platelets collected with a two-stage automated blood cell separator. PMID- 8480362 TI - Soluble proteins: size, shape and function. AB - Why are proteins so big? Why do cells build oligomeric proteins? A visual survey of the protein structures available in the Protein Data Bank sheds new light on these questions. PMID- 8480361 TI - The metabolic role of leucovorin. AB - Interest in determining if leucovorin, known chemically as 5-formyltetra hydrofolate, plays a role in one-carbon metabolism is reemerging. While investigations in the 1940s suggested it was an important donor of one-carbon units in folate-mediated biosynthetic reactions, studies between the 1950s and 1980s disproved this hypothesis and dismissed its presence in biological systems as artifactual. Recently, new data has focused attention on the possible biological function of this compound that is widely used in cancer chemotherapy. PMID- 8480363 TI - Amino acid titration curves--misshapen or mislabeled? AB - Titration curves are frequently used to illustrate the change in charge of amino acids with pH, and as such are a fundamental part of most biochemistry courses. We have noticed that the graphs of titration curves appearing in many biochemistry textbooks are drawn incorrectly near the origin of the titration. This article demonstrates that this curve is misshapen, or, alternatively, that the axis of the graph is incorrectly labelled. PMID- 8480364 TI - Protein conformation monitored by energy-selective optical spectroscopy. AB - Fluctuations in the polypeptide chain lead to disorder in proteins and to a distribution in the parameters that regulate their functions. Using low temperature (to reduce the fluctuations) and narrow-band lasers (to select one substate among the many forms), high-resolution absorption and fluorescence spectra for chromophores in proteins can be obtained. These spectra reveal information on the kind and extent of disorder in proteins and allow for the determination of the vibrational energies of both ground and excited state molecules, true inhomogeneous spectral width, and kinetic studies of individual protein substates. PMID- 8480365 TI - Hydrophobicity curvature and membrane fusion. PMID- 8480366 TI - Sequence homologies between four cytoskeleton-associated proteins. PMID- 8480367 TI - A template for the protein kinase family. AB - The crystal structure of the catalytic subunit of cAMP-dependent protein kinase, complexed with ATP and a 20-residue inhibitor peptide, is reviewed and correlated with chemical and genetic data. The striking convergence of the structure with the biochemistry and genetics provides for the first time a molecular basis for understanding how this enzyme functions, as well as an explanation for the highly conserved residues that are scattered throughout the molecule. Because these residues probably serve a common role in all eukaryotic protein kinases, this first protein kinase structure serves as a general template for the entire family of enzymes. PMID- 8480368 TI - Multiple functions of nucleosomes and regulatory factors in transcription. AB - The in vivo packaging of DNA with histone proteins to form chromatin makes its transcription a difficult process. Biochemical and genetic studies are beginning to reveal mechanistic details of how transcriptional regulatory factors confront at least two hurdles created by nucleosomes, the primary structural unit of chromatin. Regulatory factors must gain access to their respective binding sites and activate the formation of transcription complexes at core promoter elements. Distinct regulatory factors may be specialized to perform these functions. PMID- 8480369 TI - RCC1 in the cell cycle: the regulator of chromosome condensation takes on new roles. AB - In the eukaryotic cell cycle, nuclear DNA replication (S phase) and mitosis (M phase) are linked such that replication must be complete before mitosis can begin. In order for this coupling to work, there must be some system for detecting unreplicated DNA and transducing an inhibitory signal to prevent the activation of mitotic factors. The DNA-bound protein RCC1 is involved in this regulatory process since mitosis initiates before DNA synthesis is finished in the absence of RCC1. This has led to the proposal that RCC1 is a signalling molecule, detecting unreplicated DNA and producing the inhibitory signal. However, mutants in RCC1 show defects beyond their inability to regulate the cell cycle, suggesting other roles for the RCC1 protein in the nucleus and thus hitherto unexplored relationships between cell cycle control and other cellular processes. PMID- 8480370 TI - Noradrenergic mechanisms in Parkinson's disease. PMID- 8480371 TI - Ca(2+)-inhibited adenylyl cyclase in cardiac tissue. PMID- 8480372 TI - Modulation of platelet function by free radicals and free-radical scavengers. AB - Platelets have the capacity to generate oxygen-derived free radicals and are often present at inflammatory foci with other free-radical-generating cells such as white blood cells. Free radicals can modify platelet adhesion and aggregation directly or through effects on the vascular endothelium, which generates prostacyclin and nitric oxide. To defend against the overproduction of free radicals the body manufactures endogenous scavengers, which can be of enzymic or non-enzymic origin. Daniela Salvemini and Regina Botting describe how free radical scavengers may be used therapeutically to regulate the platelet reactivity involved in many pathological phenomena. PMID- 8480373 TI - Molecular characterization of the dopamine transporter. AB - Neurotransmission, which represents chemical signalling between neurons, usually takes place at highly differentiated anatomical structures called synapses. To fulfill both the time and space confinements required for optimal neurotransmission, highly specialized proteins, known as transporters or uptake sites, occur and operate at the presynaptic plasma membrane. Using the energy provided by the Na+ gradient generated by the Na+/K(+)-transporting ATPase, these transporters reuptake the neurotransmitters soon after their release, thereby regulating their effective concentrations at the synaptic cleft and the availability of neurotransmitters for a time-dependent activation of both pre- and postsynaptic receptors. The key role these proteins play in normal neurotransmission is further emphasized when the physiological and social consequences of drugs that interfere with the function of these transporters, such as the psychostimulants (e.g. amphetamine and cocaine) or the widely prescribed antidepressant drugs, are considered. In this review, Bruno Giros and Marc Caron elaborate on the potential consequences of the recent molecular cloning of the dopamine and related transporters and summarize some of the interesting properties that are emerging from this growing family of Na(+)- and Cl(-)-dependent transporters. PMID- 8480374 TI - Neuronal ATP receptors and their mechanism of action. AB - ATP stores and supplies energy in neurons, but it also acts as a transmitter molecule. ATP activates a class of membrane receptors termed P2 purinoceptors. Based on the potencies of structural analogues of ATP, P2 purinoceptors in non neuronal tissues were classified by classic pharmacological methods into two subtypes, P2x and P2y. Peter Illes and Wolfgang Norenberg report that electrophysiological investigations indicate the presence of P2y-like purinoceptors on neurons. They describe two alternative ionic transduction mechanisms that may be activated by this receptor family. PMID- 8480375 TI - Endothelins--from receptors to medicine. AB - Since the discovery of endothelins, peptides with exceptional vasoconstrictor potency that were originally suggested to act by causing the opening of Ca2+ channels, it has emerged that these agents are important in intercellular communication in many tissues. They exert their effects through G protein-coupled receptors, of which two classes have been cloned. Robert Miller, John Pelton and John Huggins review the progress made towards a molecular understanding of ligand recognition by endothelin receptors. Receptor-selective agonists and antagonists have emerged from attempts to understand the three-dimensional structure of the endothelin pharmacophore, from structure-activity studies and from rapid screening programmes. From the nature of the secretion and action of endothelins, it would seem that these peptides are involved in long-term changes rather than in acute responses to stimuli, and that they are likely to be important in a number of pathological states. Evidence suggests that receptor antagonists with appropriate affinity and selectivity may be useful in the treatment of conditions as diverse as hypertension, ulcerogenesis and ciclosporin toxicity. PMID- 8480376 TI - Current perspectives on anabolic-androgenic steroid abuse. AB - For the past 40 years anabolic-androgenic steroids have been used by a wide variety of athletes with the hope of improving their training, endurance and performance. Proponents of their use claim that the drugs increase muscle strength and mass, endurance, decrease recovery time between workouts and improve physique. Critics claim that these beneficial effects are due primarily to expectancy and other factors associated with training; many doctors also claim that their use is actually quite dangerous. Regardless of their efficacy, the use and abuse of anabolic-androgenic steroids has escalated such that in 1990 the US Congress enacted the Anabolic Steroids Control Act requiring that anabolic steroids be added to Schedule III of the Controlled Substances Act. This action placed compounds such as testosterone cipionate and nandrolone decanoate in the company of various opioid drugs, amphetamines and barbiturates. As chair of the American Society for Pharmacology and Experimental Therapeutics' Committee on Substance Abuse, Scott Lukas advocates continued research on the effectiveness, toxicity and natural history of anabolic-androgenic steroid abuse. PMID- 8480377 TI - Nonchiral, homochiral and composite chiral drugs. AB - Chirality and the implicit stereoselectivity in pharmacodynamics and pharmacokinetics, in particular of racemic therapeutics, are interesting from both scientific and applied points of view. There is much literature on the subject, including a series of papers on chirality in TiPS in 1986 (Vol. 7, pp. 20-23, 60-64, 112-116, 155-158, 200-205 and 281-285). The choice between single stereoisomers (homochiral drugs) and composite chiral drugs (mixtures of stereoisomers) depends upon therapeutic advantages (such as a reduction in xenobiotic load), possible adverse side-effects and development costs. There is a need for critical evaluation of existing and new composite chiral drugs, while the potential of nonchiral drugs is hardly discussed in the literature. This review by E. J. Ariens considers current information on composite, homo- and nonchiral drugs, with particular regard to drug development. PMID- 8480378 TI - [Chronic pelvic pain]. PMID- 8480379 TI - [Long-term prognosis for women with chronic pelvic pain without laparoscopically demonstrable cause]. AB - With the object of assessing the long-term prognosis and the frequencies of recurrence and remission in women chronic low abdominal pain without laparoscopically visible cause, questionnaire were sent in 1985 and 1991 to 55 women who had been submitted to laparoscopy in 1982-1984 for this reason. These women had been told that there was no demonstrable explanation of the pain experienced and were then discharged. 65% and 55% respectively had experienced and unfavourable course with considerable and continued symptoms. Only 22% stated in both investigations that they had experienced a favourable course and that they were, by and large, free from pain. 36% changed from an unfavourable to a favourable course or the reverse. The assessment made by the women was confirmed by a series of subordinate questions and this demonstrated a marked difference between the favourable and unfavourable courses of the condition. It is concluded that laparoscopy with exclusion of significant pathology is not, in itself, satisfactory as treatment of this patient group and that no improvement occurs in the course of time. The condition varies greatly with many recurrences and remissions and, for this reason, uncontrolled reports of the therapeutic effects are of no significance. When compared with the literature, it is suggested that this patient group should be referred early in the course of the condition to a therapist with specialist psychological/sexological insight and/or to a physiotherapist with interest in this patient group. PMID- 8480380 TI - [Ultrasound Doppler examination of the carotid artery]. AB - Ultrasound-Doppler examination of the carotid artery is employed to an increasing extent in investigation of patients with cerebrovascular disease. The diagnostic criteria and results achieved with the various forms: continuous wave Doppler, duplex scanning and colour-Doppler, are described. In the two latter methods, the accuracy is high in the diagnosis of occlusions, quantitating of all degrees of stenosis and also in identification of normal vessels. On comparison with arteriography, the accuracy is stated to be typically 85-95%. The reproducibility of the method is high and equivalent to the results obtained by assessment of the same arteriography by two independent radiologists. The sources of error are discussed and it is concluded that ultrasound-Doppler examination of the carotid artery should replace arteriography in the primary investigation of patients with cerebrovascular disease. PMID- 8480381 TI - [The immune system and physical training]. AB - The effects on the immune system of sudden physical exercise and degree of training are reviewed. During moderate as well as strenuous physical exercise natural killer (NK) cells especially, but also T and B cells are released into the blood. A few hours after moderate physical exercise the immune system is back to the pre-exercise state, but following strenuous exercise the lymphocyte concentration and the NK and B cell functions are suppressed. The immune suppression following strenuous exercise is at least partly due to release of prostaglandins from an elevated number of monocytes in the circulation. The importance of stress hormones for mediating the immune modulation is discussed. Examination of trained persons at rest show that these have elevated NK cell activity when compared to matched controls. There are sporadic reports in the literature, showing that persons who train moderately have fewer infections, while persons who train very hard have increased risk of upper respiratory diseases. These findings are in accordance with the observed immune modulation on moderate versus strenuous exercise. The effects of physical training in relation to acute and chronic diseases are evaluated. PMID- 8480382 TI - [Respiratory monitoring during sleep]. AB - A review of respiratory disorders of sleep with the possible related clinical alterations are described. Techniques and methods used in non-invasive respiratory monitoring during sleep are presented. Diagnostic events and therapeutic approaches are discussed related to special patient groups: the obstructive sleep apnoea syndrome, asthma, chronic obstructive pulmonary disease and neuromuscular diseases. PMID- 8480383 TI - [The course of bronchial asthma in adults. Factors of importance for the annual decline of lung function]. AB - The purpose of this study was to describe the relation of various factors of potential importance to the rate of decline in lung function in adults with intrinsic and extrinsic asthma. Of 180 asthmatic patients, 143 (79%) participated in a 10 year follow up examination; 94 patients had intrinsic asthma and 49 extrinsic asthma. Patients with intrinsic asthma had an annual decline in FEV1 of 50 ml, whereas those with extrinsic asthma had a decline of 23 ml; the rate of decline of lung function increased with increasing age in both groups. There was no relation between rate of decline in lung function and number of cigarettes smoked. An inverse relation between initial FEV1 and decline in FEV1 was found for the patients with extrinsic asthma but not for the patients with intrinsic asthma. A high degree of airway variability--that is, reversibility in FEV1--at the time of enrollment was found to be associated with a steeper decline in lung function in patients with intrinsic asthma, whereas increasing degrees of obstruction (decreasing FEV1/VC ratio at enrollment) and need for treatment with corticosteroids were associated with a more pronounced decline in FEV1 in patients with extrinsic asthma. The rate of decline in lung function is greater in patients with intrinsic asthma than in patients with extrinsic asthma; the prognosis for intrinsic and extrinsic asthma is to some extent influenced by different factors, which suggests that the pathogenetic mechanisms underlying intrinsic and extrinsic asthma may differ. PMID- 8480384 TI - [Nosocomial pneumonia in an intensive care unit]. PMID- 8480385 TI - [Causes of visual impairment among Scandinavian children]. PMID- 8480386 TI - [Earlier experiences with duplex scanning of femoropopliteal and crural vein bypass]. AB - Identification and correction of graft stenoses in femoropopliteal and -crural vein bypasses can prevent reconstruction failure. Sixty six consecutive vein bypasses entered a postoperative surveillance protocol, which implied clinical assessment, measurement of ankle blood pressure and duplex-scanning every three months. In 15 cases the duplex-scanning indicated graft stenoses. Seven were revised, five of which remain patent after a median follow-up of three months. Eight stenoses were observed without intervention. Five of these uncorrected stenoses (63%) thrombosed and the function of the bypass could not be reestablished. Of the 34 bypasses with normal duplex-scans only 2 (6%) thrombosed (p < 0.01 compared to observed but not revised stenosis). Neither clinical evaluation or ankle blood pressure measurement could reliably predict graft failure. This study indicates that duplex-scanning effectively identifies grafts at risk and can be expected to improve long-term patency of infrainguinal vein bypasses. PMID- 8480387 TI - [Treatment of anal incontinence with an implanted artificial anal sphincter]. PMID- 8480388 TI - [Contact tracing in HIV infection]. AB - The results of contact tracing in two male and one female HIV antibody positive index cases are described. Altogether 19 sexual partners were reported, of whom 13 were traced. In one case previously unknown HIV infection was diagnosed. Contact tracing for HIV infection in Denmark depends solely upon the cooperation of the index case and upon the willingness of notified partners to appear for counselling and testing. The efficacy of partner notification for HIV infection in Denmark based on the current strategy should be further evaluated. PMID- 8480389 TI - [Intrathoracic perforation of stomach ulcer in a massive hiatal hernia]. AB - A case of intrathoracic perforation of a chronic gastric ulcer in a hiatus hernia is presented. A 67-year-old woman had suffered from interscapular pain and epigastric discomfort following large meals for four years. During the week before admission, the epigastric and interscapular pain increased, reaching a crescendo in the 24 hours before the patient's arrival in the emergency room. Chest and abdominal x-ray showed free gas and a large hiatus hernia with an intrathoracic stomach. At laparotomy, the stomach was gently returned to the abdominal cavity, and a perforated chronic gastric ulcer was found on the greater curvature. The ulcer was excised, and the diaphragmatic crura were approximated. Apart from wound dehiscence, the postoperative course was uneventful. PMID- 8480390 TI - [Fibrinogen substitution in systemic defibrination because of thrombolysis in acute myocardial infarction]. PMID- 8480391 TI - [Incidence of schizophrenia]. PMID- 8480392 TI - [Liver in systemic lupus erythematosus]. PMID- 8480393 TI - [American turnaround in the cholesterol policy]. PMID- 8480394 TI - [Cholesterol screening--fraud or fact?]. PMID- 8480395 TI - [Neuroblastoma: epidemiology and spontaneous remission. Significance for evaluation of screening studies]. PMID- 8480396 TI - [Pravastatin--(Pravachol)--a new inhibitor of cholesterol synthesis]. PMID- 8480397 TI - Report of the RCVS working party on veterinary undergraduate education. PMID- 8480398 TI - Local secretory IgA in dogs with low systemic IgA levels. AB - Low plasma IgA concentrations are commonly found in clinically normal dogs. In order to ascertain the relative importance of local and systemic IgA concentrations as factors determining the absence of clinical signs, IgA concentrations in plasma and tears were assayed in clinically normal dogs with a deficiency of IgA (10.33 +/- 0.63 mg/dl). The IgA levels in tears (25.28 +/- 1.91 mg/dl) did not differ significantly from those of control dogs or from previously published data for dogs. Thus, low systemic levels did not imply a significant reduction in local IgA levels. The absence of clinical signs in dogs with low plasma IgA concentrations may therefore be explained by the presence of normal secretory levels and an effective immune response against local pathogens. PMID- 8480399 TI - Reduced rumination in bovine spongiform encephalopathy and scrapie. PMID- 8480400 TI - Delayed ragwort poisoning associated with lactation stress in cows. PMID- 8480401 TI - First report of kidney enlargement disease in UK goldfish. PMID- 8480402 TI - Meat hygiene service. PMID- 8480403 TI - Cyclosporin eye drops. PMID- 8480404 TI - Detection of bacterial antigens in milk. PMID- 8480405 TI - Poultry meat inspection. PMID- 8480406 TI - Bilateral optic disc colobomas and microphthalmos in a thoroughbred horse. AB - A thoroughbred colt had bilateral but unequal microphthalmos together with microcornea, abnormalities of the iris and lens and posterior segment colobomas. The case is compared with other reports of microphthalmos and coloboma in horses. PMID- 8480407 TI - Radiography as an aid in the diagnosis of traumatic reticuloperitonitis in cattle. AB - Radiographs of the reticulum, the medical records and the surgical and post mortem findings for 151 cattle were evaluated, and the radiographic findings in animals which had no pathological changes in the cranioventral abdomen were compared with those in animals with traumatic reticuloperitonitis. Features that were found to be reliable in the diagnosis of the condition included atypically positioned foreign bodies, abnormal gas shadows in the region of the reticulum, and depressions in the cranioventral margin of the reticulum. In addition to the reticulum, the remainder of the cranioventral abdomen was also assessed radiographically. An accumulation of gas or a gas-fluid interface outside the gastrointestinal tract, and intra-abdominal masses were typical findings in cattle with traumatic reticuloperitonitis. Various parameters were used to determine the reliability of radiography of the reticulum in the diagnosis of the condition; its prevalence was 50 per cent, the sensitivity of the radiographic diagnosis was 76 per cent, the specificity was 93 per cent, the accuracy was 85 per cent, the positive predictive value was 92 per cent and the negative predictive value was 80 per cent. PMID- 8480408 TI - Incidence of hydrometra in dairy goats. AB - Hydrometra or pseudopregnancy is characterised by the accumulation of aseptic fluid within the uterus and a persistent corpus luteum. In goats the diagnosis can be easily made by ultrasound. The incidence of hydrometra was investigated in three herds of dairy goats, in two of them during one oestrous season and in the other over three years. The incidence varied between 3.0 per cent and 20.8 per cent with a mean incidence of 9.0 per cent. The incidence in older goats was significantly higher than in yearlings, and the chance of a hydrometra increased with the age of the goats. The finding, during one year, that a pseudopregnancy occurred more often after an induced ovulation, was not repeated in another year. PMID- 8480409 TI - Urine retention and abdominal straining in a ewe with a pyometra and a retained corpus luteum. PMID- 8480410 TI - Possible association of metritis with periparturient subcutaneous oedema in dairy cows. PMID- 8480411 TI - Prescribing for racehorses. PMID- 8480412 TI - Sarcoptic mange. PMID- 8480413 TI - Identification of a putative cellular receptor for HTLV-I by a monoclonal antibody, Mab 34-23. AB - The ability of HTLV-I to infect cells is presumed to be dependent, in some part, on the attachment of the virus to a target cell via a specific cell surface receptor which is, as yet, unknown. Here we present evidence that a monoclonal antibody, Mab 34-23, inhibits the binding of HTLV-I to IL-2 and phytohemagglutinin-activated peripheral blood mononuclear cells and also inhibits virus entry into these cells. Analysis of a variety of target cells, including a human:mouse somatic hybrid which contains only human chromosome 17q, indicates that the binding of Mab 34-23 correlates with HTLV-I adsorption and entry. SDS PAGE and Western blot analysis show that Mab 34-23 binds to four major proteins of MW 31, 45, 55, and 70 kDa and this binding can be inhibited by HTLV-I and not HIV proteins. HTLV-I virions bind to proteins of similar molecular weight and virus-binding to these proteins can be inhibited by preincubation with Mab 34-23. These data suggest that Mab 34-23 may identify a specific cell surface receptor(s) for HTLV-I. PMID- 8480414 TI - The parvovirus H-1 NS2 protein affects viral gene expression through sequences in the 3' untranslated region. AB - We reported previously that an NS2 null mutant of parvovirus H-1 (H-1SA) was capable of lytic growth in human and hamster cells, but not in rat cells (Li and Rhode, 1991). The host-range phenotype of H-1SA was also manifested in newborn rats and was associated with a reduction of viral protein synthesis to about 10% of wild-type virus and an absence of virions in cultured rat fibroblasts. However, the H-1SA mRNAs for NS1 and capsid proteins, R1 and R3, accumulated to wild-type levels and translated well with a cell free rabbit reticulocyte lysate. These results indicate that NS2 plays an important role in the regulation of viral protein synthesis in rat cells in vivo and in vitro, but NS2 is largely dispensable in other types of cells, such as human and hamster cells. To analyze whether the 5' and 3' untranslated regions (UTR) of viral RNA are involved in the regulation by NS2, the viral VP2 gene was replaced by a reporter gene, firefly luciferase, in a plasmid clone of viral sequences and the protein synthesis under the control of P38 was evaluated by luciferase assay. Cells were transfected with luciferase expressing plasmids and subsequently infected with wild-type H-1 or H 1SA. We were able to mimic the defect in expression that we observed in cultured cells and animals with virus infection. Luciferase activity in H- 1SA-infected rat cells was about 10-fold lower than that in H-1-infected rat cells, but only 2 fold lower or less in H-1SA-infected human cells and hamster cells compared to wild-type H-1. These results are consistent with our previous data that NS2 has a host-range phenotype in the natural host of H-1, the rat. Deletion of 5' UTR sequences from P38 transcripts reduced the overall P38-luc expression but expression was NS2 independent, whereas deletion of the terminal 3' UTR sequences of viral RNA reduced NS2-dependent expression in rat cells. These results suggest that the regulation of viral protein synthesis by NS2 depends on RNA sequences in the 3' UTR. PMID- 8480415 TI - The short tail-fiber of bacteriophage T4: molecular structure and a mechanism for its conformational transition. AB - Electron microscopy, image processing and computational sequence analysis were used to investigate the structure of the short tail-fiber of bacteriophage T4. This molecule, an oligomer of gp12, is an adhesin that binds the virion irreversibly to the bacterial surface. Short tail-fibers were isolated from mutant-infected cells in which gp12 is synthesized and assembled correctly, but not incorporated into virions. Visualized in negative stain, these filamentous molecules are approximately 38 nm in total length, with an arrowhead-shaped head (approximately 10 nm long by 6 nm wide), a 24-nm shaft of uniform width (approximately 3.8 nm), and a small, seemingly flexible, tail. The primary sequence contains a domain consisting of tandem quasi-repeats, each about 40 residues long, extending from approximately residue 50 to residue 320. Molecular mass analyses by scanning transmission electron microscopy confirm that the molecule is a trimer. The masses of the head, shaft, and tail domains are consistent with (trimers of) the carboxy-terminus, the repeat region, and the amino-terminus, respectively. When short tail-fibers are visualized extending from baseplates, their heads are distal, i.e., detached, implying that it is the tail that remains in contact with the baseplate. Analysis of the molecules' curvature properties detects three hinge-sites: these suggest how the short tail fiber may be initially accommodated in a compact conformation in the "hexagon" state of the baseplate, from which it converts to the extended conformation when the baseplate switches into its "star" state. PMID- 8480416 TI - A multicomponent cis-activator of transcription of the E1b gene of adenovirus type 5. AB - We report that transcription of the adenovirus type 5 E1b gene is activated substantially in cis by sequences located between positions -362 and -49 with respect to the RNA start site. DNA fragments consisting of the -362 to -49 sequences, or subsets thereof, were inserted into a reporter plasmid containing a minimal E1b promoter (positions -48 to +14) joined to the Escherichia coli cat gene. In the presence of cotransfected E1a and E1b genes in trans, CAT enzyme synthesis in transfected KB cells was stimulated about 20-fold by sequences from 362 to -49 (XY) in cis and to a lesser extent by sequences from either -362 to 128 (X) or -127 to -49 (Y). Adenoviruses were isolated lacking the X, Y, or XY sequences and KB cells were infected with one of the mutants, as well as wild type virus to provide E1a and E1b in trans. Deletion of both X and Y resulted in a 20-fold reduction in early E1b RNA and a 12-fold reduction in late RNA. Deletion of X or Y alone produced up to 5-fold reductions in early or late E1b RNA accumulation. In vitro DNA-protein interactions in the Y sequence were revealed by modification of the procedure used for previous detection of X region footprints. These data indicate that X and Y sequences, which include E1a protein coding and 3' untranslated DNA, also participate in DNA-protein interactions necessary for high levels of E1b promoter activity. The presence of such overlapping genetic elements raises the interesting possibility that functional E1a and E1b mRNAs must be synthesized from separate templates. PMID- 8480417 TI - Infectious hepatitis B virus variant defective in pre-S2 protein expression in a chronic carrier. AB - All human hepatitis B viruses characterized so far express three envelope proteins, pre-S1, pre-S2, and HBs, which are believed to function as binding proteins for the cellular receptor, as targets for immune-mediated virus elimination, and in virion morphogenesis and secretion. Here we report the characterization of infectious HBV variant genomes that are unable to express a pre-S2 protein and which were derived from serum of a highly viremic chronic carrier. Direct sequencing of the amplified pre-S region and sequencing of 50 cloned amplified pre-S DNA fragments revealed that in all molecules, in addition to numerous nucleotide changes, there were deletions of the pre-S2 translation initiation codon and three codons 54 nucleotides downstream thereof. No pre-S2 protein and altered pre-S1 proteins were found in the serum of the patient. Cloned infectious HBV DNA genomes having the pre-S region substituted by the variant pre-S region were replication competent in cultured hepatoblastoma cells. Morphologically normal virions were efficiently secreted and were infectious for primary human hepatocyte cultures. These data demonstrate that HBV devoid of pre S2 protein can occur in vivo as a dominant or exclusive virus population and that expression of the pre-S2 protein is not essential for HBV replication, virion morphogenesis, secretion, or in vitro infectivity. PMID- 8480418 TI - Early and late gene expression in UT-7 cells infected with B19 parvovirus. AB - UT-7, a human megakaryocytoblastoid cell line, can be persistently infected with B19 parvovirus. We performed detailed serial analysis of parvovirus DNA replication and RNA transcription of synchronized cells. RNA transcription appeared as an early event following infection, with viral RNA detected about 6 hr after infection. In contrast, dimer-replicative intermediate forms of parvovirus DNA did not appear until more than 16 hr after infection. Northern analysis of specific transcripts showed an earlier appearance of nonstructural protein RNA (6 hr) compared to capsid protein RNA (24 hr). The addition of an inhibitor of protein synthesis to block synthesis of nonstructural protein abolished capsid protein RNA transcription as well as DNA replication. Primer extension analysis confirmed the initiation of all transcription from the single P6 promoter. RNA transcription precedes DNA replication of B19 parvovirus in these cells, and RNA processing may have a major role in regulating gene expression. PMID- 8480419 TI - Isolation, characterization, and mapping of temperature-sensitive mutations in the genes essential for lysogenic and lytic growth of the mycobacteriophage L1. AB - Forty temperature-sensitive mutations affecting lytic growth and eight affecting both establishment and maintenance of lysogeny of the temperate mycobacteriophage L1 have been isolated. All of the latter mutations form one complementation group and map within a very short region around the 15% coordinate of the L1 genome; these affect a single gene, cl, coding for the L1 repressor. The former 40 mutations form 28 complementation groups, identifying 28 different genes, G1-G28, essential for the lytic growth of L1. These genes have been mapped using the Gts mutations. Of the 28 Gts mutants, 14 are defective in host lysis at 42 degrees but not at 32 degrees while the other 14 can lyse the host at both temperatures. Among the former 14 Gts mutants, 6 are also defective in L1 DNA synthesis at 42 degrees, and they map in two different clusters, 4 around 65% and 2 around 84% of the L1 genome. PMID- 8480420 TI - Selection and partial characterization of dengue 2 virus mutants that induce fusion at elevated pH. AB - Two types of dengue (DEN) 2 virus mutants were selected either by repeated exposure to acidic pH (acid mutant, AM), or by the addition of ammonium chloride to Aedes albopictus C6/36 cells prior to and during viral infection (fusion mutant, FM). Both mutants grew more slowly than the parent strain and induced smaller plaques in Vero cells. The 50% fusion from within index for both mutants occurred at least 0.65 pH units higher than with the wild-type DEN virus. A single amino acid substitution (Asn-153 to Asp) was found in the envelope (E) glycoprotein of the AM virus. Three amino acid substitutions were detected on the E-glycoprotein of the FM virus: Ile-6 to Met, Asn-134 to Ser, and Asn-153 to Tyr. No mutations were found in the precursor to the membrane protein, prM. The DEN virus E-glycoprotein has two potential glycosylation sites: Asn-67 and Asn-153. The loss of the potential glycosylation site at Asn-153 or the change in the chemical characteristics resultant from the amino acid substitutions in both mutants implicates these regions of the E-glycoprotein in virus-mediated membrane fusion. PMID- 8480421 TI - Temperature-sensitive mutants in the vaccinia virus A18R gene increase double stranded RNA synthesis as a result of aberrant viral transcription. AB - Mutations in the vaccinia gene A18R cause activation of the cellular ribonucleolytic 2-5A pathway. To determine the mechanism of 2-5A pathway activation, mutant infections were analyzed for synthesis of double-stranded RNA and for transcription of individual virus genes. At late times postinfection, A18R mutant-infected cells contained an increased amount of complementary RNA and a higher steady state level of RNA from regions of the genome transcribed normally only early in the infection. The phenotype of A18R ts mutants is indistinguishable from that of wild-type infections done in the presence of isatin-beta-thiosemicarbazone (IBT). Actinomycin D is a potent inhibitor of activation of the 2-5A pathway in IBT-treated wt infections. Based on these observations, we conclude that the phenotype induced by A18R mutants or by IBT treatment of wt infections is caused by a loss of control of late viral transcription. PMID- 8480422 TI - The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees. AB - Hepatitis B virus (HBV) with an in-frame stop codon within the pre-core region of the virus genome caused fulminant hepatitis in two individuals. Serum from a chronically infected patient who was the source of the virus was inoculated into three chimpanzees at dilutions of 10(-1), 10(-3), and 10(-7). All three chimpanzees developed acute hepatitis B with relatively high peak values of liver enzymes in their serum. The complete nucleotide sequence of virus DNA recovered from the chimpanzee serum by enzymatic amplification was identical with that from the human serum. By comparing the sequence of this strain (HT) with that of 32 published HBV genomes, changes in nucleotides and predicted amino acids that were rarely or never found in other HBV isolates were identified. Thirteen such nucleotides were found within the cis-acting regulatory elements, of which 6 were within the enhancer II-core promoter region. Twenty-four rare or unique changes in amino acids were found in open reading frames, of which 15 occurred in the region that spanned the 3' half of the X gene, through the pre-core/core gene, to the 5' end of the polymerase gene. Thus, an HBV pre-core stop mutant implicated in fulminant hepatitis is highly infectious, induces severe hepatitis in chimpanzees, and possesses significant genetic variation from reported HBV isolates. PMID- 8480423 TI - Characterization of two African swine fever virus 220-kDa proteins: a precursor of the major structural protein p150 and an oligomer of phosphoprotein p32. AB - Two kinds of unrelated African swine fever virus proteins of 220 kDa have been identified by means of two-dimensional gel electrophoresis and immunoprecipitation analysis. One species, named pp220 and identified as the precursor of the major structural protein p150, was found to be a moderately acidic protein (pl near 7) expressed after the replication of the viral DNA. The second species, a cluster of 220-kDa proteins with slightly different isoelectric points (pl ranging from 5 to 6), was found to be a homooligomeric complex formed by an early 32-kDa protein. This component was identified as the viral phosphoprotein p32, the most immunogenic early protein of African swine fever virus. A detailed characterization of its oligomeric structure is reported. PMID- 8480424 TI - RNA binding of recombinant nucleocapsid proteins of hantaviruses. AB - Genes encoding the nucleocapsid (N) proteins of two hantaviruses, Hantaan virus strain 76-118 (HTN) and Puumala virus strain CG 18-20 (PUU), were expressed in Escherichia coli as histidine-tagged proteins. They were purified by metal chelate affinity chromatography under native or denaturing conditions to near homogeneity. The soluble form of HTN N protein was associated with RNA of E. coli. Renatured N proteins were shown to bind in vitro transcribed RNA representing the hantaviral small genomic (S) RNA segment. RNA binding was shown by affinity to filter-immobilized N proteins and by gel mobility shift assays. Competition experiments using tRNA, poly(U) and poly(A)+ U indicated that binding of RNA by the N protein is nonspecific. However, direct binding of ds-RNA resulted in efficient formation of large complexes suggesting that double stranded nucleic acids are bound preferentially. Carboxyterminal fragments of HTN and PUU N proteins containing about 100 amino acids of the carboxy termini retained full binding capacity indicating that RNA binding occurs via a carboxyterminal domain. PMID- 8480425 TI - HIV-1 Nef protein inhibits the recruitment of AP-1 DNA-binding activity in human T-cells. AB - The human immunodeficiency virus type 1 long terminal repeat, HIV-1-LTR, contains binding sites for several cellular transcription factors which contribute to HIV 1 gene expression. Our previous studies on the function of the HIV-1-encoded Nef protein suggested that Nef may be an inhibitor HIV-1 transcription. To determine whether Nef affects the binding of cellular factors implicated in HIV-1 regulation, 32P-labeled oligonucleotides corresponding to the binding sites were incubated with nuclear extracts prepared from Nef-expressing T-cell lines that were not stimulated or were stimulated with T-cell mitogens. We found that Nef inhibited the recruitment of AP-1 DNA-binding activity in mitogen-stimulated human T-cells. Additionally, Nef expressing cells were transiently transfected with a plasmid in which HIV-1 AP-1 DNA recognition sequences were cloned downstream of the chloramphenicol acetyltransferase (CAT) gene. Mitogen-mediated transcriptional activation of the CAT gene in this construct was inhibited in Nef expressing cells but not in control cells. These studies suggest that, by inhibiting AP-1 activation, Nef may play a role in regulating HIV-1 gene expression in infected T-cells. PMID- 8480426 TI - Mapping of the human immunodeficiency virus type 2 envelope glycoprotein CD4 binding region and fusion domain with truncated proteins expressed by recombinant vaccinia viruses. AB - Human immunodeficiency virus type 2 (HIV-2) is more closely related to certain simian immunodeficiency viruses than to HIV-1. The HIV-1 and HIV-2 envelope (env) glycoproteins share only approximately 40% amino acid (aa) sequence homology. Additionally, HIV-1 and HIV-2 seem to differ in pathogenicity and in host range. In order to identify the functional domains of the HIV-2 env glycoprotein, e.g., the CD4 binding region, the membrane anchor, and the fusion site, and to compare them to equivalent sites of HIV-1, a set of recombinant vaccinia viruses (VV) was constructed expressing N-terminal overlapping env proteins of 863 (full-length gp160), 708, 534 (full-length gp120), 438, 332, 198, and 488 aa (internal deletion of aa 333-707). Upon infection, only env proteins comprising the amino terminal half of the transmembrane protein were expressed on the cell surface. Such VV constructs also induced syncytia in CD4-positive cells. The syncytia were smaller when the cytoplasmic domain of the transmembrane protein was removed. The CD4 binding site of HIV-2 was located between the carboxy terminus of gp120 (aa 512) and aa 438. Thus the amino-terminal half of the transmembrane protein of HIV 2 is sufficient for cell surface localization of the env protein and syncytia induction. These properties are shared with the HIV-1 env protein and demonstrate a functional conservation among HIV-1 and HIV-2 despite their genetic and phenotypic heterogeneity. PMID- 8480427 TI - Selection and characterization of a neuraminidase-minus mutant of influenza virus and its rescue by cloned neuraminidase genes. AB - A neuraminidase (NA)-deficient mutant, designated NWS-Mvi, of the reassortant influenza virus A/NWS/33HA-A/tern/Australia/G70c/75NA (H1N9), was selected by passaging virus in MDCK cells in a medium containing neuraminidase from the bacterium Micromonospora viridifaciens and polyclonal antiserum against the influenza NA. Growth of the resulting mutant virus is dependent on the addition of neuraminidase to the medium. Western blot analysis showed that the neuraminidase protein was absent from the mutant virus particles, and Northern hybridization showed that RNA segment 6, which contains the coding information for the NA, had undergone massive deletion. Viral protein synthesis in cells infected with the mutant virus was not dependent on the addition of neuraminidase. In the absence of a functional NA, the NWS-Mvi mutant virus can infect MDCK cells with normal cytopathic effects. This neuraminidase-minus influenza virus serves as an excellent source of parent virus for reverse genetics experiments involving genes that encode a functional neuraminidase. PMID- 8480428 TI - RNase protection analyses show high genetic diversity among field isolates of satellite tobacco mosaic virus. AB - Fifteen field isolates of satellite tobacco mosaic virus (STMV) were collected from wild Nicotiana glauca plants within a 20-km2 area in southern California. Analyses of the entire length of the satellite genomic RNA of each isolate by RNase protection assays showed that there were 10 different genotypes within the 15 isolates, including some with regions of extreme divergence from the STMV type strain. This indicates a very high level of genetic diversity between natural STMV populations. Isolates from adjacent plants (within 3 m) were not always identical, but were more similar than those from more distant locations. Mapping of the genomic sites of heterogeneity revealed that in all cases the 3' half of the genome, which comprises the untranslated region, was more conserved than were the 5' coding regions. PMID- 8480429 TI - Structure and expression in baculovirus of the Mokola virus glycoprotein: an efficient recombinant vaccine. AB - The sequence of the glycoprotein gene of the Mokola virus, the more divergent element of the Lyssavirus genus, has been determined and the predicted protein structure compared to its counterpart in rabies vaccine strains. A global similarity of 54.3% was observed. The divergence affects particularly the rabies antigenic sites involved in the B-cell response. This provides a molecular basis for the absence of cross-protection between Mokola and rabies viruses and argues for the necessity of a specific anti-Mokola vaccine. Toward this goal, a cDNA copy of the glycoprotein gene was cloned into the baculovirus and expressed in Spodoptora frugiperda cells. A recombinant protein was produced in substantial amounts at the surface of the insect cells. Although less strongly glycosylated than the native viral glycoprotein produced in BHK-21 cells, the recombinant protein is antigenically and immunologically similar, it is recognized by specific monoclonal antibodies, and protects mice against an intracerebral challenge with Mokola virus. It therefore constitutes the first experimental genetically engineered vaccine against a rabies-related virus, and fulfills the international standard for protection. PMID- 8480430 TI - Double-stranded strong-stop DNA and the second template switch in human immunodeficiency virus (HIV) DNA synthesis. AB - Synthesis of unintegrated retroviral DNA via reverse transcription is thought to involve two separate template switches. Minus-strand strong-stop DNA, a major product of in vitro reactions using detergent-treated virions, is synthesized prior to the first template switch. Plus-strand strong-stop DNA, which is found base-paired to near full-length minus-strand DNA in infected cells, is believed to be synthesized before the second template switch. Using a synchronized, one step HIV infection model, we report here the detection in acutely infected cells of a novel double-stranded strong-stop HIV DNA with a discrete length of approximately 650 base pairs, commencing at or near the left hand end of the right-hand U3 region of the HIV long terminal repeat. The plus-strand of this double-stranded strong-stop DNA possesses the primer binding site sequence and appears to be synthesized prior to the completion of the synthesis of its complementary minus-strand. In contrast, the minus-strand of the double-stranded strong-stop DNA lacks the primer binding site sequence after RNaseH digestion. We propose that a transient free plus-strand strong-stop DNA is released from its template by displacement synthesis and subsequently used as template for the synthesis of its complementary minus-strand. The proposed transient free plus strand strong-stop DNA may also mediate the second template switch. PMID- 8480431 TI - [Unexpected and undesirable treatment results]. AB - The most frequent causes of unexpected and undesired results of treatment are due to insufficient information of the patient, furthermore, apart from technical deficiencies, to insufficient attention and experience of the physician, and to erroneous evaluation of the situation, especially with measuring out a dose of treatment-"medicus curat". On the other hand "natura sanat" comprises spontaneous healing. It's reactions of adaptation to functional stress are just partially known and, therefore, cannot be controlled safely. With insufficient incorporation of the cybernetic systems of the tissues into our planning of operations counter-reactions have to be expected, resulting in unphysiological, "unsound" operative procedures. They are characterised by relative frequent recurrences. The chances to reduce unexpected and undesired results in the "curative" and "sanative" sector are outlined. The personal experience remains most important. PMID- 8480432 TI - [Distribution pattern of subchondral mineralization in the glenoid cavity in normal subjects, athletes and patients]. AB - To get information on the stresses acting on the shoulder joint, the distribution of subchondral mineralisation was examined by means of CT-Osteo-absorptiometry in the glenoid cavity in healthy people, athletes and patients. In young persons two density maxima are found ventrally and dorsally older persons, however, show a centrally located maximum which suggests a different joint mechanics in different ages depending on the decreasing physiological incongruence. In gymnasts the overall mineralisation is significantly higher, maxima are found centrally or shifted dorsally. In patients with recurrent dislocation of the shoulder or instability the zone of highest density is shifted to the edges of the glenoid cavity indicating that the prevailing position of the resultant force is excentric. By means of CT-Osteo-absorptiometry these individual patterns of mineralisation can be displayed in the living and can give information on the individual mechanical situation ("loading history") of a joint. PMID- 8480433 TI - [Computer-assisted analysis of the kinematics of the upper ankle joint]. AB - Usually the upper ankle joint is described as a typical hinge though it had been often remarked that the axis of rotation moves considerably with regard to the angular adjustment between the tibia and the trochlea tali. In the present study the relation between the movements in the upper ankle joint and the geometry of the lateral ligaments was analysed. The contours and elected landmarks of 6 dissected ankle joints were measured using a digitizer which allowed the computerized scanning of motion x-rays. In addition the proximal and distal insertion planes of the lateral ligaments were registered. Mathematical procedures were applied on the experimental data to predict the kinematic principles. The model of an hinged joint could not reproduce the motion curve which was actually found. Using the model of a link chain with four pivots, which was determined by the course of the talofibular and the calcaneofibular ligament, a good correlation with the experimental results was evident. This model implies a rotary and gliding component in the movement of the tibia against the trochlea tali. Beside the correspondence with the data of the present study the model allows an easy explanation of many other well known morphologic phenomena of the upper ankle joint for which a stringent interpretation was not yet available. PMID- 8480434 TI - [Shoulder arthrodesis. Possible causes of functionally poor results]. AB - Due to severe articular destruction of the glenohumeral joint with corresponding soft tissue changes arthrodesis has been performed in 24 patients since 1973. After an average period of 5.4 years (2-15) years, 22 patients were reviewed. Primary bone consolidation was achieved in all cases. During the observation period in 7 cases one of the following additional operations had to be performed on the involved shoulder: subcapital osteotomy due to excessive abduction (2 cases), resection of the acromio-clavicular joint due to painful osteoarthritis (2 cases), partial resection of an ugly acromion projecting laterally (1 case), removal of the fixation plate protruding proximally (4 cases). 18 patients experienced a marked improvement after arthrodesis. No improvement in 2 cases and a deterioration in 2 cases were the result of a not optimal positioning of the arthrodesis. A position of 20 of abduction, 20 to 30 of flexion and 45 of internal rotation proved to be functionally the most beneficial. Patients will be only painless if the optimal position of the arthrodesis was achieved. Excessive abduction and flexion was generally experienced as unpleasant. Deviation in the rotational position leads to functional restriction. The remaining function after arthrodesis is often overrated. PMID- 8480435 TI - [Synovial giant cell tumor or nodular circumscribed form of pigmented villonodular synovitis?]. AB - In two case reports we demonstrate symptoms, clinical findings and treatment of patients with a benign synovial giant cell tumor of the knee and ankle joint. This tumor impresses like a localized pigmented villonodular synovitis but compared to this benign synovial giant cell tumors are rare in synovial joints and more often localized at the synovial tendon sheaths of fingers. Symptoms and clinical findings often mimic meniscal lesions. One of the most important finding is a hemorrhagic joint effusion without previous trauma. There are no typical findings in diagnostic imaging procedures and it seems that the most important fact is that the clinician is aware of this type of synovial tumor. Early resection of the tumor within wide margins is the treatment of choice. Postoperative radiotherapy is not to recommend. PMID- 8480436 TI - [Diagnosis and clinical aspects of Yersinia arthritis]. AB - Clinical and serological criteria of Yersinia arthritis are presented by a review of the literature and case studies. Characteristic findings are preceding abdominal symptoms followed by oligoarthritis of the lower extremities. 80% of patients are HLA-B 27 positive, rheumatoid factors are negative. Detection of Yersinia in stool cultures is a rare proof. The most important serological indicator is IgA for identification of Yersinia antibodies. Yersinia arthritis will resolve without sequelae under symptomatic and antibiotic (chemotherapeutic) medication within 6 months. PMID- 8480437 TI - [Are pathohistological studies helpful in the clinical differential diagnosis of chronic arthritis?]. AB - We have evaluated the diagnostic and therapeutic consequences of histopathological examinations of knee synovium from 216 patients with chronic arthropathies. We were able to differentiate between non-rheumatic etiologies, such as tuberculous arthritis, villonodular synovitis, crystal arthropathies and chondromatosis. This resulted in the establishment of a diagnosis and often a guide to therapy as well. It is rarely possible however to conclusively differentiate among the different inflammatory rheumatic diseases or osteo arthroses by the histopathology of the joint lesions seen. PMID- 8480438 TI - [Suppression of macrophage subpopulations in post-traumatic osteomyelitis]. AB - Similar to other chronic inflammatory diseases such as rheumatoid arthritis the distribution of macrophage subtypes seems to be disturbed in post-traumatic osteomyelitis. This atypical distribution is clearly locally restricted in osteomyelitis. 27E10-positive macrophages found only during the acute phase of inflammation were reduced in 39%, the 25F9-positive subtype, predominating in the late stage of inflammation, was missing in 33%. The antiinflammatory macrophage RM3/1 was decreased in 40% of the osteomyelitis biopsies. Local suppression of macrophage subsets has to be discussed as one of the reasons for the persistence of chronic inflammatory processes in osteomyelitis. PMID- 8480439 TI - [Fibrous dysplasia versus osteofibrous dysplasia. Morphological, differential diagnostic and clinical aspects. Experiences from the Westfalen bone tumor registry]. AB - Histologically, this lesion, which was first described by Campanacci, is characterized by an osteofibrous stroma replacing normal bone, showing trabeculae which, unlike in FD, are surrounded by a regular rim of prominent cubic osteoblasts, mature lamellar bone and zonal segmentation with newly formed trabeculae mostly in the cortical region. Radiologic features are eccentric, usually diaphyseally localized osteolytic lesions of the tibia with ground glass appearance. Differential diagnosis includes FD and adamantinoma. Just like OFD, the latter occurs almost exclusively in the tibia, its potential malignancy calling for a more radical therapeutical procedure. Being such a rare lesion, there are no clear guidelines regarding formal pathogenesis and therapy of adamantinoma in combination with osteofibrous stromal reaction. The mean age of the eleven patients with OFD was nine years, which is considerably lower than that of patients with FD (30 years). The lesions were found exclusively in the tibia. Surgical therapy is often followed by a recurrence of the tumor (in two cases in the present material), so it should be avoided, where possible. Thus, surgery should only be performed if complications are imminent, such as marked bone deformation or pseudoarthrosis. Unlike in FD, once bone maturation is completed, surgical treatment of OFD is not normally followed by recurrent disease. Thus, the prognosis of OFD with restricted surgical therapy is more favourable than that of FD, which frequently shows extensive skeletal involvement and recurrent disease even after many years. The more aggressive course of OFD reported by other authors must therefore be explained by too early surgical intervention, i.e. during bone maturation. PMID- 8480440 TI - [Cost analysis of a bone bank]. AB - The costs of a bone-bank working in accordance with the guidelines of the german federal chamber of physicians are described. Establishing a bone-bank storing deep-frozen bone is not very expensive. The main costs are due to laboratory costs for excluding HIV, hepatitis, syphilis and bacterial contamination of bone grafts. In our experience with 206 bone grafts about 20% of them are to be discharged because of positive laboratory tests. The costs of each bone graft are DM 327. A second HIV-Test of the donor 3 months after explantation of a bone graft will cause rising of costs up to 47%. About 20-30% of bone graft donors will probably not carry out this test. In this case discharging of the bone graft is necessary. PMID- 8480441 TI - [Damage assessment of a stainless steel lock pin]. AB - Metallurgical investigation methods were used to determine the cause of failure in a broken and explanted lock pin. Material analysis revealed that the implant material consists of a stainless steel. The fractographic investigation indicated a fatigue fracture with its typical characteristics. Macroscopic damage of the outer surface of the implant caused the fatigue fracture in the bone fracture region. Once the lock pin had failed, further crack propagation of the fatigue fracture was largely dependent on stress intensity and/or overloading of the implant in the bone fracture region as well as on the number of stress cycles. The following items should be observed by the physician applying implant materials: 1. A material showing only very small surface scratches in the order of magnitude of thousands of millimeters should not be implanted at all, because even the smallest surface roughness may cause fractures of the material. 2. Implant materials from low-cost manufacturers should never be applied. Such materials often show construction faults (in the present case an unnecessary weld in the upper part of the lock pin) or the material itself is not well conditioned (in the present case an insufficient annealing treatment). PMID- 8480442 TI - [Undesirable treatment results from the viewpoint of an expert witness on medical liability problems--an analysis of 142 cases]. AB - Causes of proven medical misconduct were analyzed on the basis of 142 expert testimonies prepared for an advisory committee on medical liability. The principal causes of misconduct identified were: 1. an incorrect indication for surgery; 2. Unsatisfactory surgical technique; 3. Inadequate preoperative patient enlightenment. In many of the cases in which an incorrect indication for therapy or a technical error could not be proved, the patients or their lawyers attempted to assert their claims by declaring that they had been insufficiently informed. The majority of the claims for recourse concerned: a) problems associated with implantation of total hip replacements; b) sequelae of revisional osteotomies of the lower extremity; c) infiltration therapy with a topical anesthetic; d) sequelae of lumbar disc surgery. These four therapeutic categories accounted for almost two-thirds of all proven errors of therapy and in informing patients. A total of 16.26% of the claims were resolved in the plaintiff's favor. Several examples are presented to illustrate the problem of incorrect indication and unsatisfactory surgical technique as a cause of proven therapeutic error. PMID- 8480443 TI - [Determination of the elasticity of the femoral cortex of Adam's arc in patients with osteoarthritis]. AB - In this study, the compressive strength, the compressive force as well as cortical thickness of prismatic specimens from Adam's arc of the femur were determined in patients with osteoarthrosis. Correlations were evaluated between the cortical bone parameters, which depend on age and sex. Supported by histomorphometric data of cancellous bone, the great variability of mechanical properties revealed the variable osteological status prior to implantation of hip endoprostheses. Its eventual consequences for alloarthroplastic surgery had been discussed. PMID- 8480444 TI - [Fracture incidence in 803 women with postmenopausal osteoporosis under drug treatment]. AB - In a survey of cases of confirmed postmenopausal osteoporosis, 803 women were asked to complete a questionnaire on radiologically confirmed fractures sustained prior to and during drug therapy. Under monotherapy (fluoride or calcium, n = 92) the number of peripheral and central fractures was 54% and 49% lower, respectively. The corresponding figures with two substances (fluoride and calcium, n = 226) were 58% and 60%, with three substances (fluoride, calcium and estrogens or Vitamin D, n = 223) 83% and 72%, and with four substances (n = 254) 85% and 75%. PMID- 8480445 TI - [Bone/cement interface reactions following several years of implantation and consequences for its fixation]. AB - Retrieved femora with fixed cemented hip arthroplasties were sectioned horizontally. Bone sections were prepared of the whole cross-sectional area to study the bone/cement-interface (bci) histologically and morphometrically. The interface between bone and cement mainly consists of a thin (< 25 microns) connective tissue layer. Demineralized zones were in parts found, this tendency seems to slightly increase in time. The bone newly formed at the bci is structured like thick trabecular bone or like dense cortical bone. A strong fixation seems possible even if a thin connective tissue layer exists, and a complete adaptation of the implant to the bone is not necessary, as the bone adapts as well. PMID- 8480446 TI - [Sterilization and the mentally handicapped: who decides?]. AB - At the moment sterilization of mentally handicapped persons is carried out in a medical and a legal vacuum in Belgium as well as abroad. To give an adequate answer to the problem of sterilization of mentally handicapped adolescents in medical practice, Dr. J. Denekens undertook an extensive literature review and an empirical investigation comprising case-studies of 52 adolescents, their parents and family doctors. The adolescents, between the ages of 16 and 21, were selected at random from students attending schools for mentally handicapped persons in the province of Antwerp during the school year 1989-1990. This study and investigation resulted in the formulation of medical and ethical criteria to assist decision makers confronted with a request for sterilization from or on the behalf of a mentally handicapped person who may be unable to decide this issue alone. These criteria have been ordered in a useful and practical algorithm that enables a motivated, logical and ethically responsible decision to be taken. A proposal of procedure for such a sterilization request has been elaborated. The medical-ethical criteria, the algorithm and the procedure proposal come out right in time as the European Parliament is discussing a motion that deals with the legal part of the subject. PMID- 8480447 TI - [Peroxisomal beta-oxidation]. AB - In animal cells peroxisomes as well as mitochondria are capable of degrading lipids via beta-oxidation. Nevertheless, there are important differences between the two systems. 1) The peroxisomal and mitochondrial beta-oxidation enzymes are different proteins. 2) Peroxisomal beta-oxidation does not degrade fatty acids completely but acts as a chain-shortening system, catalyzing only a limited number of beta-oxidation cycles. 3) Peroxisomal beta-oxidation is not coupled to oxidative phosphorylation and is thus less efficient than mitochondrial beta oxidation as far as energy conservation is concerned. 4) Peroxisomal beta oxidation is not regulated by malonyl-CoA and--as a consequence--by feeding as opposed to starvation. Peroxisomes are responsible for the beta-oxidation of very long chain (> C20) fatty acids, dicarboxylic fatty acids, 2-methyl-branched fatty acids, prostaglandins, leukotrienes, and the carboxyl side chains of certain xenobiotics and of the bile acid intermediates di- and trihydroxycoprostanic acids. Mitochondria oxidize mainly long (C16-C20) chain fatty acids, which- because of their abundance--constitute a major source of metabolic fuel. The first step in peroxisomal beta-oxidation is catalyzed by two acyl-CoA oxidases in extrahepatic tissues and by three acyl-CoA oxidases in liver, each enzyme having its own substrate specificity. Palmitoyl-CoA oxidase and pristanoyl-CoA oxidase are found in liver and extrahepatic tissues. The former enzyme oxidizes the CoA esters of straight chain fatty acids, dicarboxylic fatty acids and prostaglandins; the latter enzyme oxidizes the CoA esters of branched fatty acids but also shows some activity towards straight chain and dicarboxylic fatty acids. Hepatic peroxisomes contain a third acyl-CoA oxidase, trihydroxycoprostanoyl-CoAA oxidase, which oxidizes the CoA esters of the bile acid intermediates di- an trihydroxycoprostanic acids. Treatment of rodents with a number of structurally diverse compounds called peroxisome proliferators, results in the proliferation of peroxisomes, especially in liver, and in the induction of the hepatic peroxisomal beta-oxidation enzymes except pristanoyl-CoA oxidase and trihydroxycoprostanoyl-CoA oxidase. There exist several inborn errors, in which peroxisomal beta-oxidation is deficient. These diseases are characterized by severe neurological symptoms. The biochemical findings in these diseases confirm the function of peroxisomal beta-oxidation as described above. PMID- 8480448 TI - [The central role of the thymus in the education of T cells to neuroendocrine principles]. AB - The thymus, the lymphoid organ responsible for the induction of central T cell self-tolerance, is the site of expression of peptides belonging to the neurohypophysial peptide family. The classical model of neurosecretion established by the Scharrers for the hypothalamo-neurohypophysial axis however cannot be applied to characterize the secretory pathways of neurohypophysial related peptides in the thymic epithelial component. The novel model of cell-to cell cryptocrine signalling has recently been proposed by J.W. Funder to describe the molecular relationships between fixed epithelial cells and migratory differentiating cells. In the thymus, the cryptocrine signalling is further closely associated to the presentation of the "self" molecular structure by major histocompatibility complex-derived proteins to developing T cells. On the basis of our observations, the model of the thymic repertoire of neuroendocrine "self" antigens transposes to the molecular peptide level the dual physiological role of the thymus in T cell negative and positive selection. Moreover, this model should also contribute to a better understanding of the molecular mechanisms underlying the central T cell tolerance of "self" neuroendocrine functions. PMID- 8480449 TI - Pharmacological influences on cardiopulmonary arrest-related brain damage in the rat. AB - The aim of the present work was to evaluate the protective properties of the calcium-entry blocker nimodipine against brain damage induced by cardiopulmonary arrest in a rat model. We studied first the effect of nimodipine administered in a blind and randomized fashion and started 5 min after the restoration of spontaneous circulation. Our experiments showed no improvement of survival, and nimodipine did not improve the neurological outcome in the animals surviving after 7 days. We even observed a trend toward a decreased survival rate when higher doses of nimodipine were used. In order to evaluate whether the lack of protective effect of nimodipine might have been due to the fact that it was given too late, we administered nimodipine in the second series of experiments at the earliest feasible postischemic moment, i.e. at the start of the resuscitation attempts. However, this study also failed to show an improved outcome in nimodipine-treated animals; there was even a significantly decreased resuscitation rate. In order to exclude that a cerebroprotective effect was antagonized by deleterious effects of nimodipine on the cardiovascular system, which may be especially vulnerable after resuscitation, we also studied nimodipine in the 4-vessel occlusion model in the rat. Indeed, in contrast to the cardiopulmonary arrest model, cardiovascular depression does not occur in this model. In these experiments, we started the administration of nimodipine before the induction of global brain ischemia, used 2 different dosage regimens and provided prolonged drug administration after restoration of cerebral blood flow in order to create optimal circumstances for a cerebroprotective effect to be detected. These experiments, however, also failed to show any cerebroprotective effect of nimodipine. In this 4-vessel occlusion model, we also evaluated, as a control drug, 1,3-butanediol, an alternate substrate for brain metabolism during ischemia that has been shown to offer cerebral protection in this animal model. Our results could, however, not confirm this beneficial effect. We conclude that in the rat there is no cerebroprotective effect of the calcium-entry blocker nimodipine on global brain ischemia as present during cardiopulmonary arrest. On the contrary, we even observed adverse effects, especially when high doses are used and/or when the drug is given during resuscitation attempts. PMID- 8480450 TI - Progress in the management of ovarian cancer at the First Department of Obstetrics and Gynecology, University of Vienna, since 1955. PMID- 8480451 TI - [Embryotomy. A historical review]. AB - Destructive operations are the oldest type of bloody operation in obstetrics and possibly in the (written) history of Medicine. The name "embryotomy" is already mentioned in the hippocratic literature. The indication and technique of this "two-tempi" operation (embryotomy or reduction of the fetus and embryulcia or extraction of the reduced foetus) were thoroughly mentioned, described and coded for the first time by Soranos of Ephesos. Soranos was also the first to mention clearly by their names the instruments used. Only the Arabic physicians, especially Albucasim, transmitted to us the first image of their collection of instruments. The author elucidates the many--medical and ethical--aspects relating to embryotomy, which has been practised till after W.W.II. PMID- 8480452 TI - Production and some properties of fibrinolytic enzymes from Fusarium oxysporum N.R.C.1. AB - A mixture of yeast extract and peptone in the culture medium was the most favourable for the production of active fibrinolytic enzyme by Fusarium oxysporum N.R.C.1. Potassium dihydrogen phosphate had stimulating effect, while glucose, sucrose, lactose, ribose and soluble starch had adverse effect on enzyme productivity. The optimum of the fibrinolytic enzyme activity was at pH 7.0. PMID- 8480453 TI - Purification and properties of two fibrinolytic enzymes from Fusarium oxysporum N.R.C.1. AB - The crude fibrinolytic enzyme preparation from Fusarium oxysporum N.R.C.1 was purified into two enzymes by ammonium sulphate precipitation followed by chromatography on Sephadex G-100 and DEAE-cellulose. Both fibrinolytic enzymes were more active on human than on bovine fibrin. The activity of the "major" enzyme component on human fibrin was 72-fold that of the "minor" enzyme component. Both enzymes had the same temperature (37 degrees C) and pH (6.98) optima. The "minor" enzyme component was more stable than the "major" one against heat and pH treatments. Both enzymes were significantly activated with Co2+ and inhibited with EDTA. PMID- 8480454 TI - Fusarium poae and Fusarium sporotrichioides in cereal grains of the Slovak Republic. AB - The occurrence of Fusarium poae and F. sporotrichioides was examined in 37,172 cereal grains of 229 samples from the Slovak Republic. In an area where strains of Fusarium parasitized. 40% of grains on average, owing to unfavourable weather, 5 strains of F. poae were isolated (0.5% out of 1,015 strains of Fusarium). In an area where the situation was less unfavourable, Fusarium spp. contaminated on average 4.1% of grains, F. poae were present in 6.1% out of 82 strains of Fusarium. When cereal ripened and harvested under climatically favourable conditions. Fusarium spp. were isolated, on average, out of 3.0% of grains, but the strains of F. poae made an essential part of the mycoflora (25.5% out of 985 isolated Fusarium strains). In three samples there were ascertained 5%, 15% and 19.5% of grains contaminated by strains of F. poae, F. sporotrichioides was isolated only 5 times. PMID- 8480455 TI - Mycoflora and mycotoxin of hazelnut (Corylus avellana L.) and walnut (Juglans regia L.) seeds in Egypt. AB - Fifty-one species and 3 varieties appertaining to 20 genera were collected from 20 samples of each of hazelnut and walnut seeds on glucose- and 40% (W/V) sucrose Czapek's agar at 25 degrees C and 45 degrees C with the most common mesophiles were Aspergillus flavus, A. fumigatus, A. niger, Cladosporium cladosporioides, C. herbarum, Penicillium chrysogenum, P. citrinum and P. oxalicum. Fusarium (represented by F. equiseti, F. moniliforme and F. oxysporum) was recovered from walnut seeds in moderate frequency (on glucose-Czapek's agar). Eurotium (E. amstelodami, E. chevalieri, E. repens and E. rubrum) was completely absent on glucose agar, but it was isolated in high frequency from the two types of seeds on 40% sucrose-Czapek's agar. Aspergillus fumigatus and Rhizomucor pusillus were the most common thermophilic fungi in hazelnut and walnut seeds on glucose agar at 45 degrees C. Humicola grisea var. themoidae and Thermoascus aurantiacus were encountered rarely from walnuts. The nuts samples were assayed for natural occurrence of aflatoxins B1, B2, G1 and G2, citrinin, ochratoxin A, patulin, sterigmatocystin, zearalenone, T-2 toxin and diacetoxyscirpenol by thin layer chromatography analysis. Aflatoxin was detected in 90% of hazelnut samples (25 175 micrograms/kg) and 75% of walnut samples (15-25 micrograms/kg). Zearalenone was detected in one sample of walnut (125 micrograms/kg). This is the first report for the presence of zearalenone in walnut. The other mycotoxins were not detected. PMID- 8480456 TI - [The localization of toxin in the cells of Pasteurella multocida]. AB - The application of the degradation procedure for Gram-negative bacteria according to Bewick and Lo to Pasteurella multocida indicates that the obvious localization of the toxin is in the periplasm. The stability of the outer membrane and of the substances adhering to it is essential for the release of the toxin. The production of the toxin clearly depend on the media used. PMID- 8480457 TI - [The toxin-producing ability of salmonella from bovine test material]. AB - Cell-free supernatants of 40 Salmonella strains of different serovars were tested for the existence of enterotoxic substances in the rabbit skin permeability factor test, rabbit ileal loop test, tissue culture assays (CHO K1, RTG-2), and baby mouse test. There were differences in the test results between the strains even within the same serovar. Correlation coefficients between the results of different toxin tests were low. It is therefore improbable that the "enterotoxic activity" of Salmonella is caused by only one toxic substance. The activities revealed in the different test systems could not be related to virulence or the epizootiological behaviour of the strains. The in vitro occurrence of the virulence factor "enterotoxin production" is lower for Salmonella than for E. coli and V. cholerae. PMID- 8480458 TI - Clinical chemical diagnosis of diseases assisted by logistic regression illustrated by diagnosis of canine primary and secondary hepatobiliary diseases. AB - OBJECTIVE: The purpose of the present study was to demonstrate the use of logistic regression models in the prediction of diseases using the prediction of canine primary and secondary hepatobiliary diseases as an example. Briefly, in a logistic regression model independent variables (i.e. the analytical results) are combined in a linear equation that is used to estimate the logarithm of the odds (logit) of an event (i.e. having primary or secondary hepatobiliary disease). From the estimated logit given by the logistic regression model, a conditional probability of the event (i.e. having primary or secondary hepatobiliary disease) can be calculated. STUDY DESIGN: Twenty-six dogs with verified primary and secondary hepatobiliary diseases and 19 dogs, initially suspected to have hepatobiliary diseases, but with apparently other diseases, were included in the study. The following clinical chemical parameters were measured: alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (AP), bilirubin(Total) (TB), urea, glucose, retention of bromosulphthalein (BSP), fasting and postprandial total serum bile acid concentration (FSBA and PSBA). Logistic regression analysis, using the CATMOD procedure in SAS, was used to select which of the measured parameters should be included in the model, and to derive a logistic regression model using the selected parameters. To observe more closely the potential of the logistic regression model, the model was also used to classify a test group consisting of 13 dogs (6 dogs with hepatobiliary diseases and 7 dogs with other diseases). RESULTS: By logistic regression analysis, ASAT and PSBA were selected to be included in the final model, and the final logistic regression model was Y = -3.194 + 0.044.PSBA + 3.251.ASAT. The logistic regression model classified correctly 38 (84%) of 45 dogs in the present study. Specifically, 21 (81%) of 26 dogs with verified primary or secondary hepatobiliary diseases and 17 (90%) of 19 dogs with various other diseases were correctly classified by the logistic regression model. When the model was used on the test group, 5 (83%) of 6 dogs with hepatobiliary diseases and 7 dogs (100%) of 7 dogs with other diseases were correctly classified. CONCLUSIONS: Even though the logistic regression model derived in the present study only serves as an example, thus reducing the practical usefulness of the derived logistic regression model, the present study indicates a great potential of logistic models for the diagnosis of diseases. PMID- 8480459 TI - Determination of the fructosamine concentration in bovine serum samples. AB - The study reports on a spectrophotometric assay for the determination of serum fructosamine concentration. The assay was evaluated for use in bovine serum samples by assessment of the precision, accuracy and detectability. A reference interval for the bovine serum fructosamine concentration was also established. Further, the effect of acute changes in blood glucose on serum fructosamine concentration as well as the diurnal variations of the serum fructosamine concentration were investigated. The main conclusions can be summarized as follows: Determination of bovine serum fructosamines may be achieved by a precise and accurate assay with a detection limit well below the serum fructosamine concentration normally found in bovine sera. As a reference interval for the bovine serum fructosamine concentration 213.4 mumol/l to 265.0 mumol/l may be used. Serum fructosamine concentration is not affected by acute changes in blood glucose, and it displays no significant diurnal variation in cows. PMID- 8480460 TI - Periparturient concentrations of insulin glucagon and ketone bodies in dairy cows fed two different levels of nutrition and varying concentrate/roughage ratios. AB - High producing multiparous dairy cows were fed either diets differing in energy content or diets with identical energy and protein content but differing in roughage content at the end of the dry period and beginning of lactation. Basal insulin and ketone bodies were analysed every week from 3 weeks before to 7 weeks after calving. Pancreatic glucagon was estimated 3 weeks before, 1-3 days after, and 3 weeks after calving. Before calving the feeding regimen had a very strong influence on the basal insulin level. High amounts of concentrate increased basal insulin levels until one week before calving and caused an interruption in the physiological decreasing course. After calving the insulin levels were low in all groups of cows. Before calving there were small variations in the glucagon levels, and no influence of feeding was observed. After calving there was a strong increase, especially in the cows fed the highest amounts of concentrate. Feeding high amounts of concentrate resulted in varying and in many cases increased levels of ketone bodies in plasma. Hyperketonemic cows had lower insulin and higher glucagon levels than normal cows. The influence of non structural carbohydrates in the feed on pancreatic hormones is a cause of ketogenesis is discussed. PMID- 8480461 TI - [Effect of the storage temperature and time and the test sample materials on the LDH isoenzyme activity and protein fractions in horse blood]. AB - The LDH-isoenzyme activities and the concentration of protein fractions did not differ among heparinized plasma and serum samples of horses. In heparinized plasma samples stored at 20-22 degrees C and -18 degrees C the LDH-isoenzyme activities and the content of the protein fractions remained constant within seven days. In contrast in heparinized blood samples the total LDH activity increased markedly after seven days of storage. This increase was shared by all LDH-isoenzymes but to different extents. While the share of LDH1, LDH2 and LDH3 decreased, the proportions of LDH4 and LDH5 increased. The concentration of the protein fractions in heparinized blood samples was not affected by storage at 20 22 degrees C for seven days. PMID- 8480463 TI - Dicephalus, Arnold-Chiari malformation and spina bifida in a Japanese black calf. AB - A case of dicephalus, Arnold-Chiari malformation (ACM) and spina bifida was reported in a Japanese Black calf. Both brains and crania showed the same abnormalities as those of the monocephalic cases with ACM and were mirror-images of each other. The common findings were elongation of the brain, caudal displacement and hypoplasia of the cerebellum, dorso-ventral compression of the skull, platybasia, and enlargement of the foramen magnum. The craniolacunia was also found in our case. PMID- 8480462 TI - [Laryngeal hemiplegia in warmblood horses--a study of stallions, mares and their offspring]. AB - Laryngoscopic examination during sedation was performed on 24 stallions and on their offspring (240 foals and 474 adult horses). Additionally the dams (n = 308) of 35 foals and 216 horses were examined. With the bilateral comparison of the arytaenoid movements the function of the abductory and adductory laryngeal muscles were evaluated and the left abductory dysfunction (idiopathic laryngeal hemiplegia, ILH) was divided into six degrees. The incidence and degree of ILH depended on age and the occurrence of the same dysfunction in the parents. Foals suffered in significantly lower number (24.7 per cent) than adult horses (49.7 per cent). The progeny of unaffected parents suffered significantly less from ILH (8.9 per cent of the foals, 39.6 per cent of the adult offspring) than did comparable progeny of affected parents (41 per cent of the foals, 60.9 per cent of the adult offspring). There was no correlation between the occurrence of ILH and sex. 120 horses were examined laryngoscopically and during work to get an information about the correlation between a visible ILH and the appearance of a typical inspiratory noise. 54.3 per cent of the horses with ILH had a typical inspiratory noise. 80.9 per cent of the horse with a typical inspiratory noise showed ILH. PMID- 8480464 TI - Normal electro- and vectorcardiographic data in the growing Friesian calf using a semi-orthogonal lead system. AB - This study derives normal values for electro- and vectorcardiographic parameters, as generated by the Holmes semi-orthogonal lead system, in healthy growing calves. Sixty-four electrocardiograms were recorded from healthy Friesian calves aged from one week to one year. Waveform and duration were analysed and compared in the X-, Y- and Z-leads. The modal P, QRS and T tridimensional vectors were graphically constructed and their magnitude and orientation were calculated. The duration of waves and intervals were similar to data previously reported in the bovine species. Differences from data reported in other species were attributed to heart rate. The duration of waves and QT and ST intervals significantly lengthened with the decrease in heart rate which occurred during growth. PR interval significantly lengthened with physical maturation, and this change was independent of the decrease in heart rate. The magnitude and the orientation of the spatial modal vectors were approximately similar to the few data previously reported in cattle and in other ungulates and were not affected by somatic growth. PMID- 8480465 TI - Omega-3 fatty acid incorporation in fat and muscle tissues of growing pigs, fed supplements of fish oil. AB - Fifteen pigs from two litters of Norwegian Landrace were divided into three groups of five animals. The pigs were fed individually the same basic diet for 64 days, one group serving as control, the two other groups receiving daily supplements of 5 and 20 g fish oil, respectively. Biopsies were taken from subcutaneous fat and muscle tissues on day 0, 3, 8, 16 and 32. Samples were also collected from animals slaughtered on days 64 and 78. In fat tissue from pigs given a daily dose of 20 g fish oil containing 30% eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as triglycerides, the concentrations of EPA and DHA were significantly increased above the levels in the control animals over the 32 days period. Unexpectedly, there was also a significant increase in docosapentaenoic acid (DPA), in spite of the very low level of this fatty acid in the fish oil. In fat tissue from pigs given 5 g fish oil the contents of EPA and DPA were significantly increased. Also in muscle tissue from pigs given a daily dose of 20 g fish oil, the concentration of EPA, DPA and DHA were significantly elevated above the level of the control group over the 32 days period. In muscle tissue from pigs given 5 g fish oil only the contents of EPA were significantly increased. There was a positive correlation between the dose of fish oil and the concentrations of omega-3 polyunsaturated fatty acids in both fat and muscle tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480466 TI - Is there a place for urinary growth hormone measurement? AB - The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice. PMID- 8480467 TI - Subclinical hypothyroidism and hyperlipoproteinaemia: indiscriminate L-thyroxine treatment not justified. AB - It is still under discussion whether subclinical hypothyroidism is a biochemical syndrome or a disease associated with an increased risk for development of vascular diseases due to lipid elevation. Therefore, we investigated lipid values in 40 patients with subclinical hypothyroidism, which is defined in terms of normal (N = 26) or slightly increased (N = 14) basal TSH values and/or an exaggerated TSH response (N = 34) to TRH (> 25 mU/l). Patients with increased lipid values were treated with L-thyroxine and reanalysed three months later. Mean levels of total cholesterol. LDL- and HDL-cholesterol and triglycerides in patients with subclinical hypothyroidism were comparable with those in normal subjects. Individual analysis, however, revealed hyperlipoproteinaemia (HL) in 22.5% of the patients investigated (HL type IIa in seven, type IV in two patients). Thyroid function was the same in affected patients as in those with normal lipid values, whereas higher age was significantly more often associated with this syndrome (p < 0.01). Treatment with L-thyroxine resulted in a significant decrease in total and LDL-cholesterol (p < 0.05), although a normalization of their lipid values could be obtained only in half of the patients. None of the subjects with hyperlipoproteinaemia had a history or clinical signs of actual vascular disease. Although the incidence of hyperlipoproteinaemia in our study group of patients with mild subclinical hypothyroidism (22.5%) is comparable to that of the normal population (21.5%), it is more severe in the former group (LDL-cholesterol in patients 5.26 +/- 0.58 vs 4.8 +/- 0.56 mmol/l in controls; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480468 TI - Pancreas and gut hormone responses to oral glucose and intravenous glucagon in cystic fibrosis patients with normal, impaired, and diabetic glucose tolerance. AB - Pancreatic and gut hormone responses to oral glucose, and insulin sensitivity were studied in cystic fibrosis patients with normal (N = 14), impaired (N = 4), and diabetic (N = 12) glucose tolerance, and in 10 control subjects, and beta cell responses to oral glucose and intravenous glucagon were compared. Compared to control subjects, initial insulin and C-peptide responses to oral glucose were lower in all patient groups, and decreased with decreasing glucose tolerance. Insulin sensitivity in patients with impaired and diabetic glucose tolerance was lower than in control subjects. The 6 min post-glucagon C-peptide concentration was positively correlated with the initial insulin response to oral glucose. Fasting levels of pancreatic polypeptide, pancreatic glucagon, total glucagon, glucagon-like peptide-1 7-36 amide, and gastric inhibitory polypeptide were normal in all patient groups. Following oral glucose, pancreatic polypeptide responses were absent in all patients, suppressibility of pancreatic glucagon secretion was increasingly impaired with decreasing glucose tolerance, and gut hormone levels were normal. In conclusion, at cystic fibrosis (a) insulin secretion is impaired even when glucose tolerance and insulin sensitivity are within the normal range, (b) the glucagon test gives valid estimates of residual beta cell function, (c) pancreatic polypeptide response to oral glucose is absent, (d) glucagon suppressibility decreases with decreasing glucose tolerance, and (e) the enteroinsular axis is intact. PMID- 8480469 TI - Stimulation of mitogenesis in human thyroid epithelial cells by endothelin. AB - We investigated whether a potent vasoconstrictor, endothelin, stimulated the proliferation of human thyroid epithelial cells (thyrocytes). [3H]-thymidine incorporation into normal thyrocytes and thyrocytes from patients with Graves' disease was significantly increased at 10(-9) mol/l endothelin, reaching a plateau at 10(-8) mol/l. The proliferative responses of the thyrocytes obtained from patients with Graves' disease were similar to those of normal thyrocytes. Furthermore, the cell number of thyrocytes stimulated by endothelin was increased as compared with that of unstimulated thyrocytes. Neither indomethacin nor heparin affected this endothelin-stimulated thyrocyte proliferation. When thyrocytes were cultured with both endothelin and recombinant interleukin 1 beta, there was an additive effect on thyrocyte proliferation. The Ca2+ entry blocker, verapamil, inhibited both the proliferative responses of thyrocytes to endothelin and the additive effect of endothelin and recombinant interleukin 1 beta on thyrocyte proliferation. These results suggest that endothelin functions as a growth-promoting factor for human thyrocytes, presumably through intracellular calcium influx. PMID- 8480470 TI - Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients: vagal neuropathy or islet cell dysfunction? AB - The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response, the insulin-dependent diabetic patients were studied during normo- and hyperglycemic experimental conditions at blood glucose levels of 5 and 15 mmol/l, respectively. The PP response was identical on the two occasions, the response being significantly smaller than in the healthy subjects. Thus, PP response is independent of short term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion in insulin-dependent diabetic patients. Alternatively, the reduction in PP secretion in these patients reflects dysfunction of the PP secreting cells of the pancreas. Iv injection of cholecystokinin-8 elicited a small but significant increase in PP concentrations, while iv secretin did not increase PP concentrations at all in healthy subjects. These stimuli are therefore less suitable in the assessment of vagal neuropathy. PMID- 8480471 TI - Human early placental trophoblasts produce an epidermal growth factor-like substance in synergy with thyroid hormone. AB - Previous studies have shown that human trophoblast is the site of epidermal growth factor (EGF) localization, reception and action and that thyroid hormone exerts similar effects on trophoblasts endocrine function as observed with EGF. Thus, the present study was designed to examine local production of an EGF-like substance in synergy with thyroid hormone by early placenta. Explants of normal early (7-8 weeks) placentas were cultured in a serum-free condition in the presence or absence of L-triiodothyronine (T3), with or without cycloheximide for 4 days. The conditioned media were dialyzed, lyophilized, acidified and chromatographed over a Sephadex G-75 column equilibrated with 1 mol/l acetic acid. EGF was measured by a specific RIA for human EGF. Fractionation of the serum-free conditioned media resulted in the elution of immunoreactive EGF with an apparent molecular weight of 9,000 which is larger than [125I] human EGF. The addition of T3 (10(-8) mol/l) resulted in increased secretion of immunoreactive EGF by placental explants. By contrast, the addition of cycloheximide (5 x 10(-5) mol/l) dramatically reduced the secretion of immunoreactive EGF. The similarity of the immunoreactive EGF material to authentic human EGF was supported by parallel displacement in human EGF-RIA. These results suggest that human early placental trophoblast is capable of producing an EGF-like substance and that thyroid hormone enhances the local production of the EGF-like substance. This suggests that an autocrine/paracrine control system, wherein EGF serves as the signal in regulating placental growth and function in synergy with thyroid hormone, exists in human early placenta. PMID- 8480472 TI - Mortality in patients treated for hyperthyroidism with iodine-131. AB - Causes of death were studied in 10,552 Swedish hyperthyroid patients treated with 131I diagnosed between 1950 and 1975. The patients were followed for an average of 15 years (range 0-35 years) and were matched with the Swedish Cause of Death Register. A total of 5,400 deaths were observed and the overall standardized mortality ratio was 1.47 (95% confidence interval (CI) 1.43-1.51). The standardized mortality ratio for females was 1.50 (95% CI 1.46-1.55) compared to 1.31 (95% CI 1.23-1.39) in males. The most common cause of death (61%) was from cardiovascular diseases (standardized mortality ratio 1.65; 95% CI 1.59-1.71). Significantly elevated risks were also seen for tumours, diseases of the endocrine system, respiratory system, gastro-intestinal system, and congenital malformations. In all causes of death, except tumours and trauma, decreasing standardized mortality ratios over time were seen. Patients followed for more than 10 years had significantly elevated risks for tumours, diseases of the endocrine, respiratory, and cardiovascular systems. Patients given higher 131I activity and younger patients had higher standardized mortality ratios than those given lower activity and older patients. The hyperthyroidism per se, rather than the 131I treatment, appeared to be the major explanation for the elevated mortality. PMID- 8480473 TI - Significance of steroidogenic enzymes in the pathogenesis of adrenal tumour. AB - We examined both activities and amounts of steroidogenic cytochrome P-450s at the posttranslational protein level and steroid contents in the adrenocortical adenoma from patients with primary aldosteronism and Cushing's syndrome. Aldosterone synthase cytochrome P-450 (human P-450aldo) was detected in the tumour portion of aldosterone-producing adenoma, but not in the normal control adrenals, at the protein level. Neither the activities nor the amounts of other P 450s in the tumour portion of aldosterone-producing adenoma were significantly different from those in the non-tumour portion in the adenoma and the normal control adrenals. The aldosterone content was significantly elevated, while the androstenedione content was significantly decreased in the tumour portion of the adenoma compared with that in the normal control adrenals. In Cushing's syndrome, both the activities and amounts of P-450(17 alpha) and P-450c21 were significantly elevated in the tumour portion compared with the non-tumour portion of the adenoma and the normal control adrenals, while those of P-450scc and P 450(11 beta) in the tumour portion were not significantly different from the normal control adrenals. The cortisol content was significantly elevated, while the amounts of aldosterone and 18-hydroxydeoxycorticosterone in the tumour portion of the adenoma were significantly decreased compared with those in the normal control adrenals. These results demonstrate that overexpression of P 450aldo in aldosterone-producing adenoma, and those of P-450(17 alpha) and P 450c21 in cortisol-producing adenoma may play some role in the pathogenesis of primary aldosteronism and Cushing's syndrome, respectively. PMID- 8480474 TI - Heterogeneity of neuropeptide Y immunoreactivity in patients with pheochromocytoma: influence on the diagnostic power of measuring plasma NPY using antisera with different specificities. AB - The nature of NPY-like immunoreactivity (NPY-LI) was investigated in plasma and tumour tissue of 17 pheochromocytoma patients by HPLC, gel filtration and isoelectric focusing using two radioimmunoassays (RIAs) directed against the C- and N-terminals of NPY respectively. The two RIAs gave similar results in pheochromocytomas: 86% of cases had higher NPY-LI concentrations than those found in normal adrenal glands and NPY-LI behaved like authentic human NPY during gel filtration and HPLC. Assessed by isoelectric focusing, NPY was found to be amidated in seven of nine tumours. Contrary to the findings obtained in tumours, the results of the two RIAs in plasma samples were not always concordant: compared to controls, elevated concentrations of NPY-LI were found in 86% of cases of pheochromocytomas using the C-terminally directed RIA and in 76% of cases using the N-terminally directed RIA. The results of HPLC and gel filtration of NPY-LI in plasma suggested that circulating C- and N-terminal NPY fragments account for the discrepancy between the results of the two RIAs. In conclusion, most pheochromocytomas contain large amounts of NPY-LI that behaved like authentic NPY by chromatographic analysis. On the contrary, circulating NPY-LI in some pheochromocytoma patients is heterogeneous with cleaved products which influence differently the power of the C- and N-terminally directed RIAs for the diagnosis of pheochromocytoma. PMID- 8480475 TI - Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients. AB - In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1 +/- 3.2, placebo vs 103.3 +/- 3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2 +/- 0.2 vs 5.7 +/- 0.2 mmol/l, p < 0.01), serum insulin (168.0 +/- 14.5 vs 138.9 +/- 7.9 pmol/l, p < 0.05), serum C-peptide (0.68 +/- 0.03 vs 0.58 +/- 0.02 nmol/l, p < 0.05) and total serum cholesterol (6.07 +/- 0.41 vs 5.48 +/- 0.38 mmol/l, p < 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p < 0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p < 0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU.kg-1 x min-1) glucose disposal rate tended to be increased (18%, p = 0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss. PMID- 8480476 TI - Effects of tibolone on serum concentrations of lipoprotein(a) in postmenopausal women. AB - OBJECTIVE: To evaluate the effects of tibolone (Org OD14), a synthetic steroid used for the relief of postmenopausal symptoms, on serum concentrations of lipoprotein(a) (Lp(a)), an independent risk marker for coronary heart disease. DESIGN: Subset of women participating in a non-randomized prospective trial of tibolone therapy. Twenty-seven women requesting relief of menopausal symptoms were treated with tibolone 2.5 mg/day for six months; 27 women who did not request treatment acted as controls. RESULTS: Tibolone induced a substantial fall (p < 0.001) in serum Lp(a) levels (median change -48%, range -100% to +3%). CONCLUSIONS: In terms of cardiovascular risk, the ability of tibolone to lower serum concentrations of Lp(a) may be advantageous in view of the unwanted reduction in high density lipoprotein concentrations which has previously been demonstrated in users of this steroid. PMID- 8480477 TI - The effect of single doses of inhaled beclomethasone dipropionate on the circadian rhythm in serum osteocalcin in normals. AB - A single dose of 2.5 mg prednisone leads to a significant transient decrease in serum osteocalcin, which is only demonstrated by frequent serum sampling. The aim of the present study was to evaluate whether a single dose of inhaled beclomethasone dipropionate causes transient changes in serum osteocalcin, indicating a systemic effect on bone cells. In a double-blind, placebo controlled, cross-over design we evaluated the effects of single doses of 250 micrograms and 1000 micrograms beclomethasone on the circadian rhythm in serum osteocalcin. Fifteen normal subjects aged 23-38 years were studied twice with an interval of one week with hourly blood sampling from 16.30 until 17.00 the following day; 1000 micrograms beclomethasone, but not 250 micrograms, suppressed serum cortisol by 14.4 +/- 6.7% (p = 0.03). Neither of the beclomethasone doses significantly altered the time pattern of serum osteocalcin. We conclude that a single inhaled dose of beclomethasone in the therapeutical range does not acutely influence osteoblastic activity as judged from serial measurements of serum osteocalcin. PMID- 8480478 TI - In vivo acute testicular testosterone response to injection of luteinizing hormone in the rat fetus. AB - The acute in vivo testosterone response to LH stimulation and its change during late fetal life were determined in the rat. In 18.5-day-old fetuses, testicular testosterone content was increased in a dose- and time-dependent manner after fetal subcutaneous LH injection. The maximum response was small: the testicular content and plasma concentration were increased by 200% and 250% over basal values respectively, while they were increased 1100% and 1200% in adult rats. Similarly, comparable low responses were obtained after subcutaneously injecting the fetuses with human chorionic gonadotropin (hCG) and after injecting LH into the vitelline vein. Between days 18.5 and 21.5 of fetal life, the testosterone levels in the testis and plasma of uninjected or PBS-injected fetuses decreased and were comparable in both groups. In maximally LH-stimulated fetuses, the testicular content did not change with age, and plasma concentration was lower on day 21.5 than on day 18.5. Since the number of Leydig cells increases 1.5 to 2 fold between days 18.5 and 21.5, these results show an age-related decrease in basal and maximally LH-stimulated in vivo testosterone secretions per Leydig cell during late fetal life. PMID- 8480479 TI - Biological and immunological properties of the international standard for FSH 83/575: isoelectrofocusing profile and comparison with other FSH preparations. AB - The new international standard for FSH, IS 83/575, has been analyzed, after isoelectric focusing separation, by Sertoli cell in vitro bioassay, radioligand receptor assay and two highly specific immunometric assays. Its molecular composition was then compared with the isoelectric focusing profiles obtained from the fractionation of the reference preparation 2nd IRP 78/549 and from pools of human male and female pituitary extracts and male and female sera. The results showed that > 80% of immunoreactive and bioactive FSH in the IS 83/575 has a pI value < 4, while such very acidic material was represented much less in the other FSH preparations tested. All the immunoreactive material contained in the IS 83/575 was shown to be capable of receptor binding and bioactivity in vitro. A generally good correspondence between IEF profiles obtained by bioassay and by immunofluorimetric assay was evident in the case of IS 83/575, 2nd IRP 78/549 and pituitary extracts, although the profiles recorded by immunofluorimetric assay were rather smooth and more isoforms were detected by bioassay. A striking discrepancy between immunoreactive FSH and bioactive FSH was observed after isoelectric focusing fractionation of the serum pools, in which some bioactive material was not detected by immunofluorimetric assay and some of the immunoreactive FSH peaks were devoid of bioactivity, indicating that serum contains inhibitors of FSH action and that immunometric assays based on monoclonal antibodies may miss some bioactive FSH isoforms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480480 TI - Low-dose recombinant alfa-2a-interferon: a feasible maintenance therapy in acute myeloid leukaemia in the older patient. AB - Eleven patients with acute myeloid leukaemia (AML) in first complete remission (CR) were treated with alfa-2a-interferon (for short 'interferon') maintenance therapy, at a dose of 3 MU twice to thrice weekly subcutaneously. Adjustments were made to maintain neutrophil counts > 1 x 10(9)/l and platelet counts > 100 x 10(9)/l. A transient fall in haemoglobin, neutrophil and platelet counts was noted in all 9 evaluable patients. Median time to nadir was 7 weeks. Initial dosage reductions were necessary in 5 patients, 3 of whom were later able to tolerate the starting dose. No episodes of infection or bleeding were documented during therapy and no red cell or platelet transfusions were necessary. At the time of writing (median follow-up of 31 weeks), 7 patients continue in CR, 6 of whom remain on interferon. One patient discontinued interferon on developing sicca syndrome. Other than in this patient, side effects were minor. Mean dose administered was 6.7 MU/patient/week. We conclude that low-dose IFN maintenance therapy is well tolerated in older patients with AML in first CR. PMID- 8480481 TI - Changes in plasma levels of prothrombin fragment F 1 + 2 in cases of disseminated intravascular coagulation. AB - Plasma levels of prothrombin fragment F 1 + 2 (PTF) and thrombin-antithrombin III complex (TAT) were assayed in 86 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, which suggested that the in vivo generation of thrombin is highly accelerated by the cleavage of the prothrombin molecule by factor Xa. On the contrary, no significant elevation of plasma levels of PTF was observed in cases of DIC with severe hepatic failure or fulminant hepatitis in spite of significant elevation of TAT. Plasma levels of PTF were directly proportional to those of TAT in 86 cases of DIC as a whole (r = 0.682, p < 0.001). The measurement of both parameters was considered to be useful to estimate the hemostatic activation in DIC. PMID- 8480482 TI - Expression of fibronectin and adhesion to fibronectin in myeloma cell lines. AB - Fibronectin (FN) expression in six myeloma, two mature B-cell lines, and four T cell lines was analyzed. All myeloma cell lines expressed FN at various levels, while mature B- and T-cell lines apparently had less FN. Moreover, an extramedullary plasmacytoma-derived myeloma cell line, KHM7, was found to secrete FN into the culture medium. Fibronectin receptors, VLA4 or VLA5, were expressed at various levels on all myeloma cell lines. An adhesion assay revealed three of six myeloma cell lines bound to FN. However, there was no correlation between binding to FN and FN receptor expression, indicating a complicated FN binding pathway. The mechanism and pathological significance of FN expression and FN binding in myeloma cells are discussed. PMID- 8480483 TI - Recurrent transient bone marrow hypoplasia associated with pregnancy. AB - A 24-year-old female was admitted for evaluation of thrombocytopenia during her second pregnancy. During the second trimester of her first pregnancy, the patient developed aplastic anemia which resolved completely following termination of pregnancy. Three and a half years later she was admitted in the third trimester of pregnancy suffering from severe thrombocytopenia and hypoplastic bone marrow which improved after a normal delivery. To the best of our knowledge this is the first description of recurrent bone marrow hypoplasia associated with pregnancy. PMID- 8480484 TI - Atypical hereditary ovalocytosis associated with defective dyserythropoietic anemia. AB - The cases of a child and his mother affected by chronic anemia with atypical elliptocytosis are reported. When adolescent the mother underwent splenectomy, with an incomplete response. Anemia was characterized by a morphological picture of ovalocytosis associated with a significant percentage of spherocytes in the peripheral blood of the child and spiculated red cells in that of the splenectomized mother. Bone marrow aspirates of the child showed a striking erythropoietic hyperplasia with marked decrease of mature cells and dyserythropoietic features. Reticulocyte count was rather low. Ferrokinetics showed ineffective erythropoiesis. Biochemical studies on red blood cell membrane cytoskeleton showed that beta-spectrin, alpha-spectrin and protein 4.1, which are usually altered in hereditary elliptocytosis (HE), were normal in our cases. This report confirms the hypothesis of Torlontano who postulated the existence of a distinct atypical form of HE associated with ineffective and dysplastic erythropoiesis. PMID- 8480485 TI - Severe osteoporosis and multiple vertebral collapses in a child during treatment for B-ALL. AB - The incidence of bone lesions at diagnosis of childhood acute lymphoblastic leukemia (ALL) is relatively high. However, no cases of severe osteoporosis with multiple vertebral collapses secondary to treatment in children with ALL have been reported. We report the case of a 9-year-old-boy with B-ALL, with no bone lesions at the diagnosis that, following the 4th block of aggressive chemotherapy (protocol B-ALL BFM 86), presented severe back pain and functional impairment with diffuse osteoporosis and vertebral collapses. He was treated with calcitonin, vitamin D, calcium, physical therapy and orthopedic corset. Osteoporosis progressed slowly during the following 2 months of chemotherapy and the boy developed dorsal kyphosis. After discontinuing antiblastic treatment progressive clinical improvement was observed, with complete resolution of kyphosis in about 6 months. An almost complete bone recovery was seen on X-ray survey at 26-months follow-up. PMID- 8480486 TI - Myelodysplastic syndrome with thrombocytosis in a patient with Klinefelter's syndrome. AB - We report herein a patient with Klinefelter's syndrome associated with refractory anemia with excess of blasts in transformation, a subtype of myelodysplastic syndrome (MDS). The MDS developed with karyotypic abnormality involving t(4;7)(q21;q11), and was characteristic of marked thrombocytosis and marrow infiltration by many atypical megakaryocytes. The patient also had diabetes mellitus and a disturbed immune system. To our knowledge, this is the fifth reported case of MDS in patients with Klinefelter's syndrome in the literature. PMID- 8480488 TI - In vivo evidence of all-trans retinoic acid inducing maturation in acute promyelocytic leukaemia. AB - All-trans retinoic acid therapy induces maturation in acute promyelocytic leukaemia. We document in vivo evidence of differentiation by all-trans retinoic acid in a case of acute promyelocytic leukaemia which was characterized by cytoplasmic vacuolations. PMID- 8480487 TI - B-type large-cell primary splenic lymphoma with massive involvement of the red pulp. AB - A B-type large-cell primary splenic lymphoma with massive red-pulp involvement was diagnosed in a 64-year-old woman presenting with malaise, fever, anemia, atypical lymphoid cells in peripheral blood, and splenomegaly. This case differs from most splenic lymphomas both macroscopically and microscopically. At macroscopic examination, the spleen was homogeneously red without tumoral nodules or masses. Microscopically, the cords of the red pulp were extensively invaded by tumor cells maintaining patient sinuses. The white pulp was reduced by expansion of the red pulp. To our knowledge only few additional cases of splenic lymphoma with similar features have been previously described. The differential diagnosis of this unusual form of lymphoma with other lymphoproliferative disorders is briefly discussed. PMID- 8480489 TI - A rapid method for the detection of alpha I/65 hereditary elliptocytosis. PMID- 8480490 TI - Proteins C and S in two different vaso-occlusive disorders. PMID- 8480491 TI - Treatment of acute idiopathic thrombocytopenic purpura with high-dose methylprednisolone and immunoglobulin. AB - In childhood idiopathic thrombocytopenic purpura (ITP), both intravenous high dose steroids and immunoglobulin treatments have been demonstrated to raise platelet counts reliably and in most cases within 72 h, when used as separate therapeutic modalities. However, until now, the preferred emergency management of life-threatening complications in children with ITP has been immediate splenectomy. Since steroids and immunoglobulin create a partial splenic dysfunction, through different mechanisms, we investigated whether combined treatment with both drugs could produce a rapid platelet count increase comparable to that of splenectomy. Eleven patients, ages 4 months to 6 years, with a diagnosis of acute ITP were entered into this pilot study. Treatment consisted of intravenous high-dose methylprednisolone (20 mg/kg in 30 min) followed by intravenous gamma globulin (Gamimune-N, 1 g/kg over 5 h). The combined therapy resulted in rapid increments in the platelet counts of all patients within the 24-hour period. At 12-h, in particular, 9/11 patients had platelet counts of 30 x 10(9)l or more. We conclude that this combined therapy provides a prompt rise in platelet counts to a safe and hemostatic level and may offer a viable alternative for emergency splenectomy and its associated morbidity/mortality in many cases of childhood ITP. PMID- 8480492 TI - Lung permeability and other pathophysiological lung problems in shock. PMID- 8480493 TI - Kidney function in shock. PMID- 8480494 TI - Manipulation of the immunoinflammatory reaction in clinical sepsis. AB - For many years patients with sepsis and septic shock have been treated with antibiotics, fluids, surgery (if indicated) and, in the more severe cases, inotropic and ventilatory support. During recent years there has been an intensive development of new treatments based on increased knowledge of the pathophysiology. This presentation will focus on treatments modulating the immunoinflammatory response, which are either available in clinical practice today or which will be available in the near future. It is concluded that optimal therapy depends on the stage of the septic disease as well as the gram stain of the causative bacteria. PMID- 8480495 TI - Volume substitution in shock. AB - Shock treatment seems optimal when a "balanced" fluid and volume regimen, including both crystalloid (Ringer's acetate) and about 3% colloid, is used. Dextran is the colloid of choice due to its beneficial effects on plasma volume, hemorheology, and microvascular blood flow. Dextrans exert, in addition, inhibiting effects on the shock- and trauma-induced activation of the cascade system, whereby the risk of complications in the form of multiple organ failure is reduced. Infusion of red blood cells, plasma or thrombocytes should be based on a proper assessment of each individual patient's actual need of oxygen transporters and coagulation factors. PMID- 8480496 TI - Oxygen transport in severe sepsis. PMID- 8480497 TI - The pathophysiology of shock. AB - Trauma often includes considerable losses of blood and plasma that may lead to hypovolemia and shock. The initial response of the body to trauma and hemorrhage is characterized by a neuroendocrine-mediated general defence reaction for the maintenance of circulatory homeostasis and substrate availability for vital organ function. Endogenous fluid is mobilized from intracellular and interstitial sources into the vascular compartment. This transcapillary refill is achieved by activation of glucose osmotic and neurogenic adaptive vascular mechanisms. The metabolic consequences of insufficient tissue perfusion are anaerobic glycolysis with increased production of lactate and hydrogen ions, acidosis, impaired mitochondrial energy production, disturbed ionic homeostasis across cell membranes, and reduced functional capacity of tissue cells. The shock- and trauma induced alterations in tissue perfusion and metabolism vary, depending on the autoregulatory capacity of an organ, its basal metabolic requirements, its high energy phosphagen reserves, and its ongoing functional activity. Metabolic alterations impairing organ function occur early in the kidney and the liver and late in the heart and the brain. The ischemic tolerance of the skeletal muscle cell is considerable but vast amounts of lactic acid are produced, which at reperfusion will reach central blood and disturb vital organ function. Tissue factors released from mechanically traumatized or hypoxic cells will activate cascade systems and may induce alterations in remote organs, i.e. result in the development of multiorgan failure. PMID- 8480498 TI - Optimization of oxygen transport to the tissues. PMID- 8480499 TI - Cascade system activation in shock. AB - Trauma and sepsis activate different cascade systems. Activation of the coagulation and clotting systems, of the kinin-kallikrein system and of the complement system are important etiological mechanisms behind development of the adult respiratory distress syndrome (ARDS) and multisystem organ failure (MOF) after extensive trauma or severe septic situations. Activation of complement with the release of anaphylatoxins and terminal complement complexes is associated with increased mortality and development of ARDS and MOF after major surgery and in situations of septic shock. The anaphylatoxins have potent vascular properties and they activate leukocytes. Their effects on the leukocytes lead to the release of free oxygen radicals, different lysosomal enzymes and cytokines, leukotrienes and histamine. All these inflammatory mediators may, if released in extensive amounts, induce microvascular injury and interstitial edema. If this process takes place in the lung, ARDS may develop and if other organs, i.e the liver and the kidneys, are involved, MOF may be the result. PMID- 8480500 TI - Physiological aspects of vascular endothelial cell interactions in hypertension and atherosclerosis. AB - Hypertension causes a number of alterations of the coronary circulation which may influence the outcome of anaesthesia and surgery. These include changes in the architecture of the coronary vasculature, and impairments in coronary reserve and autoregulatory ability of the coronary microvasculature during decreases in perfusion pressure. Chronic hypertension may also alter endothelial regulation of vascular control. Many of the vasodilators used to treat hypertension may have unique effects on the coronary circulation which may become modified by chronic hypertension and cardiac hypertrophy. In this review, each of these areas are considered together with some unique aspects of endothelial/vascular smooth muscle interactions as they relate to acute and chronic hypertension, and to the pharmacological agents used in the treatment of hypertension. PMID- 8480501 TI - Therapies for perioperative hypertension: pharmacodynamic considerations. AB - Cardiac output (CO) and peripheral resistance (PR), the two major determinants of systemic arterial blood pressure (BP), are regulated principally by the adrenergic (ADR) and renin-angiotensin-aldosterone (RAA) systems. Antihypertensive medications ultimately decrease CO, PR, or both, by acting at various sites in the ADR and RAA pathways or affecting cardiovascular functions directly. Beta-ADR-receptor blockers decrease heart rate (HR) and stroke volume (SV) by preventing the cardiostimulating effects of catecholamines and inhibiting renin release. Alpha-ADR-receptor blockers prevent the vasoconstricting effects of catecholamines and reduce PR (afterload). Angiotensin-converting enzyme inhibitors (ACEI) block the formation of angiotensin, a potent peripheral vasoconstrictor and aldosterone releaser. Hence, ACEI cause a decrease in both PR and CO, the latter by preventing salt and water retention by aldosterone, thereby reducing plasma volume and venous return. Direct vasorelaxation and, thus, a fall in PR can be achieved by vasodilators. These include drugs (e.g. calcium antagonists) that prevent the entry of calcium ions into vascular smooth muscle cells, and others (e.g. nitrovasodilators) that boost the intracellular levels of vasodilating second messengers (e.g. cyclic GMP). Antihypertensives from different classes are often combined to improve the ratio between therapeutic and adverse effects. PMID- 8480502 TI - The ideal agent for perioperative hypertension and potential cytoprotective effects. AB - Perioperative hypertension is primarily due to increased systemic vascular resistance (SVR). Therefore, the major therapeutic approaches are directed at reducing vasoconstriction, using drugs that increase cyclic nucleotides or block calcium entry into vascular smooth muscle. Nitroprusside and other nitric oxide derived vasodilators affect both the resistance vessels and the vascular capacitance bed. Antihypertensive drugs that affect venous return can have unpredictable effects on blood pressure and calculated SVR. The new intravenous dihydropyridine calcium antagonists have arterial vasodilating actions and are especially promising as new therapeutic approaches for perioperative hypertension. Following coronary bypass-grafting, patients have undergone direct mechanical manipulation of their native grafts, coronary arteries, and internal mammary artery, creating a potential risk for coronary or internal mammary spasm. Calcium antagonists may be an important therapy for perioperative hypertension in such patients. Experimental models have demonstrated that calcium antagonists can attenuate the production of inflammatory mediators and thereby reduce cellular damage following reperfusion. These potential anti-inflammatory drugs may prove to offer additional benefits in the therapy of perioperative hypertension. The potential anti-inflammatory and cytoprotective effects of calcium antagonists may make them the ideal agents for the treatment of acute perioperative hypertension. PMID- 8480503 TI - Isradipine: a profile in essential hypertension. AB - Isradipine is a new dihydropyridine-derived calcium antagonist. It possesses marked vascular selectivity, resulting in a powerful vasodilating action, whereas, in practical terms, it is devoid of cardiac effects. The usefulness of isradipine in the treatment of arterial hypertension is well documented, both when used as single-drug treatment and in combination with other agents, particularly, beta-blockers. Isradipine is well tolerated and does not negatively affect quality of life or capacity for physical exercise. It does not cause metabolic disturbances and, apart from the typical dihydropyridine-type vascular side-effects, specifically, flushing and ankle oedema, there are no specific adverse effects. Even ankle oedema is apparently relatively rare with this compound. Studies in animal models show that isradipine has a potent anti atherosclerotic effect, and a brain tissue-preserving effect after experimental stroke, in doses that are relevant for antihypertensive treatment. If such results can be confirmed in humans, they will undoubtedly be of great clinical importance. PMID- 8480504 TI - Haemodynamics and tissue specificity with isradipine. AB - The significant effects of isradipine in producing arterial vasodilation and mild negative chronotropic effects without significant negative inotropic effects suggests that this agent should provide excellent antihypertensive efficacy in the treatment of perioperative hypertension. Isradipine may prove to be a safe antihypertensive treatment in patients with impaired ventricular function (cardiac failure), impaired myocardial perfusion (ischaemia), and in cases of selected conduction abnormalities or arrhythmias. The demonstration that its effects are limited to vascular resistance rather than vascular capacitance is an important distinguishing feature of isradipine compared with other antihypertensive agents. Finally, the potential application of this dihydropyridine calcium antagonist for cytoprotection and its effects on atherosclerosis remain exciting therapeutic prospects. PMID- 8480505 TI - Isradipine and the coronary circulation. AB - Isradipine has been shown to be an effective vasodilator in different vascular beds. Experimental evidence suggests that isradipine is a potent coronary vasodilator, and this is supported by clinical studies in both cardiology and cardiac surgery. Furthermore, in these studies, coronary vasodilation was not accompanied by evidence of any significant effect on cardiac contractility or conduction. It can be concluded that the cardiac effects of isradipine will ultimately prove to be beneficial in patients undergoing myocardial revascularization. PMID- 8480506 TI - A randomized comparative study of the electrophysiological and electrocardiographic effects of isradipine vs verapamil. AB - Isradipine is a new dihydropyridine calcium antagonist reported to have minimal effects on cardiac electrophysiology. Of 19 patients with normal cardiac electrophysiological profiles, 11 received isradipine intravenously at doses of 0.0010, 0.0020, 0.0040 and 0.0080 mg.kg-1 (0.0150 mg.kg-1 total dose), and eight received verapamil intravenously at 0.0125, 0.0250, 0.0500 and 0.1000 mg.kg-1 (0.1875 mg.kg-1 total dose). One patient experienced hypotension several minutes after receiving the third isradipine dose. With isradipine, systolic blood pressure (BP) decreased from 154 +/- 24 to 151 +/- 22, 143 +/- 25, 133 +/- 19 and 124 +/- 17 mmHg, respectively. Diastolic BP decreased from 83 +/- 10 (baseline) to 80 +/- 12, 76 +/- 10, 74 +/- 7 and 68 +/- 9 mmHg, respectively. With verapamil, systolic BP changed from 132 +/- 20 (baseline) to 135 +/- 29, 132 +/- 24, 130 +/- 25 and 115 +/- 17 mmHg, respectively, and diastolic BP changed from 80 +/- 14 to 84 +/- 14, 81 +/- 9, 78 +/- 6 and 73 +/- 5 mmHg, respectively. Isradipine had no significant effect on the PR, QRS, QT and QTc intervals, nor were there changes in the atrial-His (AH) and His-ventricle (HV) intervals, atrioventricular nodal effective refractory period. Wenckebach cycle length or sinus node recovery time. Similarly, verapamil at the doses studied did not significantly affect PR, QRS, QT, QTc, AH or HV intervals. However, with verapamil, the Wenckebach cycle length changed significantly from 394 +/- 82 (baseline) to 448 +/- 93 ms. Despite the significant fall in BP with isradipine, heart rate did not change significantly. These results support the electrophysiological neutrality of isradipine on the cardiac conduction system. PMID- 8480507 TI - Comparative study of isradipine and sodium nitroprusside in the control of hypertension in patients following coronary artery-bypass surgery. AB - Essential hypertension is a common occurrence after coronary artery bypass-graft surgery. CABG and may lead to postoperative complications. In an open randomized study, either isradipine or sodium nitroprusside was given by infusion to 27 postoperative CABG patients who had a mean arterial pressure (MAP) greater than 100 mmHg. Both agents were able to achieve reductions in MAP to 80-90 mmHg quickly and safely, although the effects of isradipine at the dosage used were apparent sooner and gave smoother control than with sodium nitroprusside. There were two non-responders with the latter agent. Systemic vascular resistance fell and cardiac output increased in patients in both treatment groups. Also, an increase in heart rate was observed with both agents, although this increase was smaller with isradipine. In conclusion, isradipine appears to be a useful agent in the treatment of hypertension following CABG surgery and may have some advantages over sodium nitroprusside. PMID- 8480508 TI - Incidence and aetiology of perioperative hypertension. AB - The reported incidence of perioperative hypertension associated with coronary artery bypass-graft (CABG) surgery ranges from 30-80%, which may reflect the various definitions of the condition as well as differences in the patients' preoperative states. Systolic, diastolic and mean arterial blood pressures are variously used to define perioperative hypertension, but absolute values range from a target systolic blood pressure of below 170 mmHg in some studies to below 110 mmHg in others. Patients' preoperative states have been extensively studied to determine potential risk factors. The majority of these studies indicate that perioperative hypertension is predictive of perioperative cardiac morbidity, but others do not confirm this finding, rendering the issue unresolved. The consequences of perioperative hypertensive episodes include bleeding from vascular suture lines, cerebrovascular haemorrhage or subendocardial ischaemia, and are associated with a mortality rate that may approach 50%. Increases in peripheral vascular resistance (PVR), caused by elevated levels of circulating catecholamines, appear to be the primary aetiology. Antihypertensive agents which correct or prevent the increase in PVR would appear to be the most appropriate therapy. However, no single agent appears to be ideal for all hypertensive episodes, suggesting multiple potential aetiologies. PMID- 8480509 TI - Gliofibromas (including malignant forms), and gliosarcomas: a comparative study and review of the literature. AB - The presence of connective tissue elements in gliomas necessitates in every case a thorough analysis of the character and derivation of such elements to allow the formulation of an appropriate diagnosis. Four cases are presented in this paper. In cases 1 and 2 (anaplastic astrocytomas in two children, 9 and 4 years old, respectively) all the neoplastic elements were astrocytes and their ability to produce or indirectly promote the production of reticulin and collagen fibers accounted for the presence of such elements in close association with the tumor cells. The term "gliofibroma" has been coined for such tumors, but "desmoplastic astrocytoma", (low grade or anaplastic) or in highly malignant cases "desmoplastic glioblastoma", as the case may be, also seem to be appropriate terms for such neoplasms. In contrast, cases 3 and 4 represented composite tumors in adults (66 and 58 years old, respectively) and the neoplasms of these patients consisted of glioblastoma and sarcoma, the latter component demonstrably being of vascular origin. This is the type of tumor usually referred to as gliosarcoma or "Feigin tumor". Although some apparent similarities between the two groups may exist at times, the histogenesis of the latter group's sarcomatous or sarcoma like portions is different from that of the first group and, therefore, warrants separate diagnostic terms and placement in brain tumor classification. PMID- 8480510 TI - Colocalization of cholinesterases with beta amyloid protein in aged and Alzheimer's brains. AB - The colocalization of beta amyloid protein with the enzymes acetyl- and butyrylcholinesterase was assessed using immunocytochemistry for beta amyloid protein and a sensitive histochemical technique for cholinesterases. In non demented aged and Alzheimer's disease brains, double-stained sections for cholinesterases and thioflavin-S showed that all thioflavin-S-positive plaques were also positive for cholinesterases, indicating the presence of these enzymes in all plaques with beta-pleated amyloid protein. When amyloid angiopathy was present, cholinesterases were also observed in amyloid-laden vessels walls. Comparison of series of adjacent sections alternatively stained for acetylcholinesterase, beta amyloid protein and butyrylcholinesterase, as well as by double histo-immunocytochemical staining, showed either cholinesterase in a proportion of the preamyloid diffuse plaques. These data indicate that cholinesterases are associated with the amyloid protein from very early stages, when the beta-pleated structure is being formed. Novel functions attributed to acetyl- and butyrylcholinesterase, such us their proteolytic activity either by themselves or in association with heparan sulfate proteoglycans, may play a role in the aggregation or the consolidation processes taking place at the early stages of diffuse plaque formation. PMID- 8480511 TI - The possible role of lysosomal enzymes in the pathogenesis of hypertensive cerebral lesions in spontaneously hypertensive rats. AB - In an attempt to clarify the role of lysosomal enzymes in the developmental mechanisms of cerebral lesions under chronic hypertensive conditions, we biochemically investigated the activities of acid phosphatase (AcPase), N-acetyl beta-glucosaminidase (NAGase) and cathepsin B (CathB) in the cerebral cortex and subcortical white matter in stroke-prone spontaneously hypertensive rats (SHRSPs). We also investigated enzyme-histochemically the activities of AcPase and NAGase, and immunohistochemically the distribution of CathB. The activities of all enzymes tended to increase with advancing age. The enzyme activities in the aged SHRSPs were in general higher than those in normotensive rats, the differences being significant at 24 weeks of age. Histochemical investigation showed that SHRSPs had an increased number of cells with positive reaction to these enzymes in the edematous cortex with and without vascular changes, and degenerated subcortical white matter. These cells with positive reaction were made up of reactively increased astrocytes and microglia. Neurons in the edematous area also showed slightly intensified enzyme activities. The present studies suggest that chronic hypertension or chronic edema due to hypertension causes increased activities of lysosomal enzymes in the cerebral cortex and subcortical white matter and, thus, that activated lysosomal enzymes may take part in the developmental mechanisms of cystic formation as well as the diffuse degeneration of the white matter. PMID- 8480512 TI - Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings. AB - We report three siblings born with severe neonatal encephalopathy, manifested clinically by microcephaly, myoclonus, and muscular hypertonus. Karyotypic analyses and all biochemical investigations were unrevealing. All three patients died during infancy. Postmortem examination of the brain in one child disclosed severe neuronal loss in the inferior olives and the pontine nuclei. There was also severe hypoplasia of the cerebellum and micrencephaly. There was diffuse gliosis of the white matter in all areas of the brain. We believe this may represent a previously undescribed form of familial infantile encephalopathy with olivopontocerebellar hypoplasia. PMID- 8480513 TI - Columnar arrangement of beta-amyloid protein deposits in the cerebral cortex of patients with Alzheimer's disease. AB - The spatial pattern of beta-amyloid protein (BAP) deposits in Alzheimer's disease cerebral cortex was investigated. In cortical areas where the accumulation of BAP was relatively sparse, the deposits tended to accumulate vertically in a columnar arrangement. Typically, these aggregates consisted of both consolidated and diffuse deposits approximately 200 to 600 microns in width. Blood vessels running perpendicularly to the pial surface were sometimes observed penetrating the center of these columns, but this was not a consistent finding. These BAP extracellular aggregates might be related to the columnar organization of the cerebral cortex. PMID- 8480514 TI - Experimental emetine myopathy: enzyme histochemical, electron microscopic, and immunomorphological studies. AB - Ipecac, containing emetine hydrochloride, is used by patients with anorexia nervosa to induce vomiting. Its chronic usage may result in a myopathy and a cardiomyopathy, the former marked by cytoplasmic bodies. We studied myopathological changes after daily injections of female Wistar rats with emetine hydrochloride intraperitoneally for periods of 4, 5, 9, and 10 weeks. The extensor digitorum longus muscle and the soleus muscle showed core-like lesions, streaming of the z-discs, nemaline bodies, cytoplasmic bodies, and spheroid cytoplasmic bodies. Immunomorphological studies revealed increased amounts of desmin. During a period of repair, i.e., 2, 4, and 6 weeks after termination of emetine application, these myopathological alterations faded while proliferation of the T-tubular system, i.e., honeycomb structures, was more often prevalent. Pathological features completely disappeared between 6 and 12 weeks of recovery. PMID- 8480515 TI - Ultrastructural neuropathology of chronic wasting disease in captive mule deer. AB - Chronic wasting disease (CWD), a progressive and uniformly fatal neurological disorder, is characterized neuropathologically by intraneuronal vacuolation, spongiform change of the neuropil and astrocytic hyperplasia and hypertrophy. Ultrastructural neuropathological findings consist of (1) extensive vacuolation in neuronal processes, within myelin sheaths, formed by splitting at the major dense lines or within axons; (2) dystrophic neurites (dendrites, axonal preterminals and myelinated axons containing degenerating mitochondria and pleomorphic, electron-dense inclusion bodies); (3) prominent astrocytic gliosis; (4) amyloid plaques; and (5) giant neuronal autophagic vacuoles. Other findings include activated macrophages and occasional spheroidal structures containing densely packed fibrillar material of unknown origin, abundant structures suggestive of degenerating microtubules entrapped in filamentous masses, vacuoles and myelin figures. Similar findings have been previously observed in scrapie infected hamsters and Creutzfeldt-Jakob disease (CJD)-infected mice, bovine spongiform encephalopathy, and CJD indicating that CWD in captive mule deer belongs to the subacute spongiform encephalopathies (transmissible brain amyloidoses). PMID- 8480516 TI - An early cytoplasmic change before Lewy body maturation: an ultrastructural study of the substantia nigra from an autopsy case of juvenile parkinsonism. AB - Neurons containing a central pale area which may possibly represent an early cytoplasmic change before Lewy body maturation were observed in the substantia nigra from a rare autopsy case of juvenile parkinsonism. Ultrastructurally, such neurons exhibited cytoplasmic swelling along with disappearance of the rough endoplasmic reticulum from the central part of the perikaryon. The pale central cytoplasm was replaced by numerous-cored vesicles, mitochondria, ribosome-like granules and a few Lewy body filaments. The relation of this central pale area to the pale body is discussed. PMID- 8480518 TI - [Treatment of obstructive processes of prostatic origin with the Fabian prosthesis]. AB - The present report is a contribution of our experience on the use of Fabian's prothesis. All patients had a urethral obstructive process which resulted from a hyperplastic or carcinomatous prostatic disease for which open- or endoscopic surgery was totally contraindicated due to the patients' general status as a result of major cardiorespiratory disorders. A literature review and an evaluation of both indications and contraindications for using such prothesis was made. PMID- 8480517 TI - Cortical tubers demonstrate reduced immunoreactivity for synapsin I. AB - To evaluate the effects of tuberous sclerosis (TS) on cortical synaptic organization, we analyzed synaptic densities within cortical tubers from the brains of two TS patients using a polyclonal antibody directed against synapsin I, a synaptic terminal-specific protein. The synaptic densities of the tubers and adjacent histologically normal cortex were obtained by determining optical densities using an IBAS (Zeiss) image analysis system. The tubers showed abnormally low levels of synapsin I compared with the normal cortex. The data suggest that cortical tubers do not contain a normal complement of synapses. This may reflect focal underdevelopment of normal cortical-cortical connections. Altered afferent cortical projections may also contribute to synaptic loss in cortical tubers. PMID- 8480519 TI - [Blue nevus of the prostate]. AB - The presence of melanin in the prostatic gland's stroma is a histopathological finding of extreme rarity. It receives the name of blue nevus as a result of its similitude to the skin's blue nevus. The paper describes the finding of melanin stores in the fibromuscular stroma of a patient's prostate and reviews the theories on its source. PMID- 8480521 TI - [Acute colonic pseudo-obstruction (Ogilvie syndrome) after nephrectomy for renal carcinoma: persistence after decompressive colonoscopy and spontaneous remission]. AB - A 65-year-old male patient presented acute dilatation in the ascendant colon on the third post-operative day following nephrectomy due to renal adenocarcinoma. No changes in colonic diameter were seen after decompressive colonoscopy and, while the patient was asymptomatic, conservative therapy was instituted and the picture was resolved in just a few days. The case is used to review the issue of acute colonic pseudo-obstruction and its relationship to urological operations. PMID- 8480520 TI - [Cyst of the seminal vesicle. Importance of transrectal echography in this type of malformations]. AB - Presentation of one case of seminal vesicle cyst with no associated anomalies. Review of diagnostic procedures useful in this type of disease, illustrating the relevance of transrectal ultrasound scanning due to its high specificity and low morbidity. Comments on the therapeutical options for this entity. PMID- 8480523 TI - [Acquired cystic renal disease, bilateral spontaneous renal hemorrhage, and functional renal transplantation. Review of the literature and report of a case]. AB - Presentation of one case of bilateral, retroperitoneal, intracystic and spontaneous renal haematoma in a patient with acquired renal cystic disease (ARCD) and renal transplantation with functioning graft. A literature review is made with regard to the association of ARCD and spontaneous renal haematoma in dialysed patients; also an analysis of the etiopathogenic factors, as well as diagnostic and therapeutical approaches to the above association. No reference has been found in the literature of concomitant ARCD, bilateral spontaneous renal haemorrhage and renal transplantation with functioning graft. PMID- 8480522 TI - [Urothelial carcinoma after treatment with cyclophosphamide. Review of the literature and presentation of our caseload]. AB - Cyclophosphamide has been used since 1958 in the treatment of various malignant tumours and certain systemic diseases, toxicity to the urothelium, frequently causing haemorrhagic cystitis and less often urothelial carcinomas, being one of its most notorious side effects--some 60 urothelial carcinoma cases have been published following therapy with cyclophosphamide since 1971. The present paper is a contribution of two new cases and its raises the need of paying special attention to urinary manifestations as well as narrowing the cooperation between the physicians which prescribe cyclophosphamide and the urologist, in order to make an appropriate follow-up and management of the patient. PMID- 8480524 TI - [Gastrocystoplasty for renal insufficiency in adults]. AB - Vesical substitution or augmentation with various segments from the gut is a frequent occurrence in urology. In the presence of normal renal function there are few or no metabolic disorders. In the presence of renal failure the most suitable gut segment is the stomach due to its characteristics of Cl- and ammonium excretion, smaller mucus formation, acid pH provided to the urine and because it allows easy ureteral regrafting. This article contributes one case of gastrocystoplastia in a patient with trigonal bladder and chronic renal failure, presenting reno-vesical TB. PMID- 8480525 TI - [Congenital prepubic sinus: blind epispadial duplication of the urethra]. AB - Presentation of one case of congenital epispadial urethral duplication in a 1 year old child. The malformation consisted on one normal urethra and the other one a prepubic epispadial accessory urethra, with the proximal end finishing blind into the anterior side of the bladder. The mictional cystography performed showed normal bladder and urethra, while the retrograde urethrography through the dorsal sinus showed a 3 cm long tract with no communication to the urethra or the bladder. Treatment consisted in total exeresis of the accessory urethra by way of suprapubic approach, with no symphysiotomy. Up to the present date, the patient remains asymptomatic. PMID- 8480526 TI - [Urologic surgery without hospitalization]. AB - The improvement of surgical utensils, the development of endoscopic techniques, the simplification of many surgical procedures and the increasing substitution of classic surgery with treatments using the physical effects originated from innovative devices, together with the evolution of anaesthetic techniques, make possible for urological operations to be now simpler and less aggressive. All of what, whenever both the hospital and the social environment so allow it, can let us in many cases dispense with hospitalizations which, up to now, were considered essential or, at any rate, significantly reduce the patient's stay in hospital. PMID- 8480527 TI - [Medical and surgical aspects of renal lithiasis]. AB - Over the last ten years a true revolution has developed in the resolution of renal and excretory tract calculi. Modern technology has made available to urologists a wide variety of procedures to be used for the fragmentation and removal of calculi, providing few complications, and more satisfaction and speed. The results have surprised urologists, patients and the entire community, up to the point where all interest in the etiological diagnosis and medical management of the lithiatic condition has been lost. Treatment, however, can only be considered complete when formation of new calculi is stopped; and progress to achieve this objective has also been relevant. The purpose of this paper is to explain the reasons for which surgical and medical management should not be competitive but complementary. Surgical procedures are directed to existing calculus, whereas medical measures focus on prophylaxis. PMID- 8480528 TI - [Current controversies on the treatment of urinary lithiasis]. AB - With the discovery during the 1960s of an access to the renal sinus and intra operative radiological monitoring, the lithiasis surgery reached its summit of technical perfection. A comparative study on the various therapeutical options is presented: NLP, URN, ESWL and open surgery, as the single or combined treatment in complex renal lithiasis. Also, intrasinusal and transparenquimatous accesses to the intrarenal tract are compared, evaluating the morbidity, surgical time and economical interpretation of both techniques. Establishment of each treatments' indications and contraindications as well as likely short- and long-term adverse effects of the new technologies. PMID- 8480529 TI - Report of the 14th meeting of the British Inflammation Research Association. Topic: cellular and molecular aspects of inflammatory bowel disease. PMID- 8480530 TI - Muramyldipeptide and granulocyte-macrophage colony-stimulating factor enhance interferon-gamma-induced nitric oxide production by rat alveolar macrophages. AB - Rat alveolar macrophages incubated with recombinant rat interferon-gamma produce L-arginine-dependent nitric oxide, which is rapidly decomposed into nitrite: this production by interferon-gamma was markedly enhanced by granulocyte-macrophage colony-stimulating factor and muramyldipeptide, but not by other cytokines. The enhancement was dependent on the presence of L-arginine in the incubation medium. It was based on a simple synergism between interferon-gamma and muramyldipeptide and a priming effect of granulocyte-macrophage colony-stimulating factor for interferon-gamma-induced nitrite production. These data suggest that cytokine networks are important in the induction of nitric oxide in rat alveolar macrophages. PMID- 8480531 TI - Pharmacologic manipulation of a four day murine delayed type hypersensitivity model. AB - A murine delayed-type hypersensitivity (DTH) model was developed as a tool for drug discovery. Time course studies indicated that hind paw swelling was maximal at four days post-sensitization with picryl chloride. A pharmacological survey involving daily administration of drugs revealed that as a class, the glucocorticoids (e.g. dexamethasone and corticosterone) were the most potent inhibitors of the DTH response. The immunosuppressants, methotrexate, cyclosporine A, cyclophosphamide, and azathioprine, were all able to suppress the DTH response, with methotrexate being the most potent suppressor of paw swelling. Likewise, non-steroidal anti-inflammatory agents (e.g. indomethacin, piroxicam, diclofenac, and naproxen) all suppressed the DTH response, with indomethacin and piroxicam being the most potent suppressors. A series of central nervous system affecting drugs, including serotonin agonists [e.g. trifluromethylphenylpiperazine (tfMPP), 1-(3-chlorophenyl)piperazine (mCPP), quipazine, and 8-hydroxy-DPAT hydrobromide (8-OH DPAT)], and serotonin antagonists (e.g. cyproheptadiene, ketanserin, and mianserin) were examined in the 4 day DTH model. Except for 8-OH DPAT, all of the serotonin agonists were able to suppress the DTH response, with mCPP being the most potent suppressor. In contrast, none of the tested serotonin antagonists had any effect on the DTH response. The histamine antagonists (e.g. cimetidine and chlorphineramine) were largely ineffective in suppressing the DTH response. These data provide a pharmacological profile for a series of immunomodulator, non-steroidal anti inflammatory, and central nervous system active compounds in a classic immunologic model. PMID- 8480532 TI - In vitro effects of hyaluronan on prostaglandin E2 induction by interleukin-1 in rabbit articular chondrocytes. AB - Effects of hyaluronan (HA) on the prostaglandin E2 (PGE2) production induced by recombinant human interleukin-1 beta (rhIL-1 beta) in rabbit articular chondrocytes were studied in vitro. The rhIL-1 beta-induced PGE2 production was dose-dependently inhibited by HA. HA with the highest molecular weight (M(r) = 2.0 x 10(6)) exhibited an inhibitory effect that was statistically more significant than the same polymer of lower molecular weights (M(r) = 1.0 x 10(6), 0.5 x 10(6)). This effect was observed in both young and adult rabbit articular chondrocytes. Since PGE2 has been implicated as a mediator of inflammatory joint diseases, our observations suggest that HA may elicit an anti-inflammatory effect by inhibiting PGE2 production. PMID- 8480533 TI - The use of angiostatic steroids to inhibit cartilage destruction in an in vivo model of granuloma-mediated cartilage degradation. AB - Angiogenesis is an important component of the development of chronic inflammatory diseases such as rheumatoid arthritis. It is known that clinically used anti rheumatic drugs exert, in part, effects on the angiogenic response. Little work, however, has investigated the potential of experimental angiostatic therapies in chronic inflammatory disease models. The effect of one such angiostatic treatment, cortisone combined with heparin, was tested in an in vivo model of granuloma-mediated cartilage degradation. Angiostatic treatment significantly retarded the growth of granulomatous tissue, mononuclear cell influx into the granuloma, and the degradation of juxtaposed cartilage. This correlated with a decrease in the vascularity of the granulomatous tissue. Modulation of this component of pathogenesis of "angiogenesis-dependent disease" may be useful as a new therapeutic approach. PMID- 8480534 TI - Therapeutic potential of protein kinase C inhibitors. AB - The serine/threonine protein kinase, protein kinase C (PKC) is a family of closely related isoforms which are physiologically activated by diacylglycerol generated by the binding of a variety of agonists to their cellular receptors. Free fatty acids may also play a role in activating PKC. The enzyme apparently mediates a wide range of signal transduction processes in cells and, therefore, inhibitors directed selectively against PKC may have wide-ranging therapeutic potential. This review highlights the evidence that inappropriate activation of PKC occurs in a number of disease states. Such evidence, however, is often seriously flawed because it relies on the use of phorbol esters, which are potent and direct PKC activators but may not mimic the physiological triggering of the enzyme in cells, or on the use of non-selective protein kinase inhibitors such as H7 and staurosporine. A new generation of bis-indolylmaleimides, derived from the lead provided by staurosporine, shows a high degree of selectivity for PKC over closely related protein kinases and such agents may provide more appropriate tools to investigate the role of PKC in cellular processes. PMID- 8480535 TI - Airway inflammation induced by xanthine/xanthine oxidase in guinea pigs. AB - Airway inflammation is suggested to play an important role in bronchial asthma. However, there is poor documentation about the effects of reactive oxygens on airway tissues in aspect of airway inflammation. Presently, we investigated whether aerosolized xanthine (X)/xanthine oxidase (XOD) induces airway inflammation in anesthetized guinea pigs. Inhalation of X for 5 min followed by inhalation of XOD for 5 min was performed with an ultrasonic nebulizer in anesthetized animals. Airway inflammation was assessed by airway vascular permeability using Pontamine sky blue. Inhalation of X/XOD produced a marked Pontamine sky blue exudation in the trachea, main bronchus and lungs. The X/XOD induced increase in Pontamine sky-blue exudation was attenuated by pretreatment with inhaled catalase, but not by superoxide dismutase. Additionally, in the bronchus and lungs, the increase in Pontamine sky-blue exudation was significantly suppressed by deferoxamine. The above results indicate that hydrogen peroxide and hydroxyl radical converted from superoxide anion cause an intense airway inflammation. PMID- 8480536 TI - Identification of tissue kallikrein messenger RNA in human neutrophils. AB - Expression of tissue kallikrein in human neutrophils has been suggested by previous studies using enzymatic and immunochemical techniques. Secretion of this potent biological factor by neutrophils would be of marked significance in the inflammatory process. The present study utilized the polymerase chain reaction following reverse transcriptase generation of total neutrophils cDNA to demonstrate the presence of tissue kallikrein mRNA in the human neutrophils. In addition, use of sequence-specific primers demonstrated the presence of mRNA for the hGK-1 gene, but not for the hPK gene product or the gene for prostate specific antigen. These results confirm that tissue kallikrein is present in neutrophils and may be secreted as part of the inflammatory process. PMID- 8480537 TI - Release of polyamines in cultures of rat parotid and liver cells. AB - Rat parotid gland and liver cells were cultured for 6 and 24 h. The cells as well as their growth medium were analyzed on their content of the polyamines putrescine, spermidine and spermine. In control medium the content of polyamines was very low but already after 6 h substantial amounts of all three polyamines under study had been released into the medium from parotid as well as from liver cells. The release was much more pronounced from parotid compared to liver cells. Putrescine was accumulated in parotid cells as well as in the medium indicating that a new synthesis of this amine occurred in these cells. PMID- 8480538 TI - Rat paw edema and leukocyte immigration induced by plant lectins. AB - Lectins from Dioclea grandiflora (DG) and Canavalia brasiliensis (CB) were compared with Concanavalin A (ConA) for their ability to induce paw edema and peritoneal cell immigration in rats. ConA caused a slight edema with a peak at 1 h after injection, while DG or CB induced a pronounced and long-lasting edema that reached a maximum at about 6 h. Different antiinflammatory drugs partially inhibited the edema. alpha-D-glucose (GLU) partially blocked the edema caused by ConA and markedly inhibited that due to CB, but had no effect on the edema induced by DG. alpha-Methyl mannoside (alpha-MM) blocked the edema caused by DG and ConA, but did not affect that caused by CB. At doses much lower than those used to induce paw edema, the lectins promoted an intense accumulation of neutrophil and mononuclear cells in the rat peritoneal cavity. CB and DG were more potent than ConA, which also presented a different profile of cell immigration. GLU significantly inhibited leukocyte accumulation caused by all lectins. alpha-MM impaired ConA- and DG-induced cell immigration, but only partially inhibited CB. Thus, despite their physicochemical similarities with ConA, DG and CB have more powerful pro-inflammatory effects. This difference seems to be related to their sugar-binding properties. However, while ConA- and DG-induced effects were inhibited more by alpha-MM than by GLU, CB-induced effects were inhibited more by glucose. PMID- 8480539 TI - Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack. AB - In vitro models of pancreatic islet cell inflammation are the lysis of isolated islet cells by activated macrophages or by oxygen radicals released by the endothelial enzyme xanthine oxidase. Dihydrolipoic acid protected islet cells in both systems by different modes of action. Macrophage cytotoxicity towards islet cells, which is nitric-oxide-mediated, was suppressed by 2 h of preincubation of macrophages with lipoic acid. Similarly, 2 h of preincubation sufficed to protect islet cells against enzymatically produced oxygen radicals. Dihydrolipoic acid was found by chemiluminescence assay to scavenge directly such radicals. In macrophages dihydrolipoic acid suppressed the production of nitrite as a measure of nitric oxide release. These results suggest that dihydrolipoic acid is an anti inflammatory agent which at the same time interferes with nitric oxide release from inflammatory macrophages and protects target cells from oxygen radical attack. PMID- 8480540 TI - Effect of BW B70C, a novel inhibitor of arachidonic acid 5-lipoxygenase, on allergen-induced bronchoconstriction and late-phase lung eosinophil accumulation in sensitised guinea-pigs. AB - The actions of BW B70C, an orally available, biologically persistent and selective inhibitor of arachidonic acid 5-lipoxygenase, have been examined in two systems of anaphylaxis in actively sensitised guinea-pigs in vivo. In anaesthetised, artificially ventilated animals pretreated with mepyramine and indomethacin to leave only the "peptidoleukotriene-dependent" component (leukotrienes C4, D4 and E4) of the anaphylactic response, direct inhalation of nebulised allergen resulted in a slowly developing bronchoconstriction which was prevented in a dose-dependent manner by BW B70C (2-50 mg/kg p.o.) administered 1 or 6 h before challenge. In conscious animals fasted overnight and then pretreated with mepyramine to prevent death due to acute bronchial anaphylaxis, exposure to nebulised allergen produced slight respiratory symptoms. When blood and lung samples were analysed 4-48 h after allergen provocation a sustained leukocytosis and pulmonary eosinophil accumulation were observed. In contrast, in food-replete conscious animals, the early respiratory symptoms were still observed upon allergen inhalation, but no significant blood leukocytosis or accumulation of eosinophils in the lungs occurred subsequently. The eosinophil influx induced by allergen in fasted animals was assessed both by histological examination and determination of tissue peroxidase content, two measures which demonstrated reasonable agreement. Administration of a single dose of BW B70C (10 mg/kg p.o.) 1 h prior to allergen challenge did not affect the subsequent eosinophil infiltration 24 h later, but 20 mg/kg given in divided doses (-1 and +12 h) produced 67% inhibition of cell accumulation. A single dose of 50 mg/kg ( 1 h) had a similar effect (78% inhibition). The potent glucocorticosteroid betamethasone was used as a reference compound, and 4 mg/kg given as a divided dose (-1 and +7) fully inhibited lung inflammation assessed 24 h after provocation with allergen. BW B70C inhibited both acute and allergic bronchoconstriction and late-phase eosinophil accumulation subsequent to allergen inhalation in guinea-pigs. In view of the apparent requirement for sustained plasma levels of BW B70C in order to prevent late-phase eosinophil recruitment to the lung after a single challenge with allergen, it is unclear whether inhibition of 5-lipoxygenase underlies the observed anti-eosinophil accumulation effects of the compound, but the anti-bronchoconstrictor effects are consistent with the known inhibitory activity of BW B70C against 5-lipoxygenase. PMID- 8480541 TI - Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role. AB - The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-L-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-L-arginine assay, (2) significant inhibition of lambda-carrageenan hind-paw oedema and croton-oil induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections. PMID- 8480543 TI - Update on childhood asthma. PMID- 8480542 TI - The retinoic acid analog CBS-211A potentiates the 1 alpha,25-dihydroxyvitamin D3 induced differentiation of U937 cells. AB - We report the effect of CBS-211A, a synthetic retinoid analog, designed for topical eye administration, on the growth and differentiation of myelomonocytic cells. This compound was assayed alone or in combination with 1 alpha,25 dihydroxyvitamin D3 (1 alpha,25(OH)2D3), since we previously evidenced a synergism of retinoic acid (RA) and 1 alpha,25(OH)2D3 in the induction of U937 cell differentiation. Unlike RA, CBS-211A neither affected the growth of myelomonocytic cells nor differentiated them. Nevertheless, when it was associated with 1 alpha,25(OH)2D3, CBS-211A strongly potentiated the 1 alpha,25(OH)2D3-induced inhibition of U937 cell proliferation and caused a dramatic increase in their differentiation toward monocytes/macrophages. The co inducing effect of CBS-211A was restricted to U937 cells. Our data suggest that CBS-211A may have therapeutic implications in the treatment of certain kinds of myelomonocytic leukemia. CBS-211A also provides an interesting tool to understand the mechanisms involved in the differentiation of myelomonocytic cells. PMID- 8480544 TI - Changing pattern of asthmatic symptoms during childhood--different diseases? PMID- 8480545 TI - Airway inflammation, bronchial reactivity and asthma. AB - Asthma is a common disease of children the basis of which is a state of chronic immunological inflammation which causes bronchial hyperreactivity and renders the patient liable to develop widespread airways obstruction in response to a variety of stimuli. In many instances it is likely that the immunological inflammation results from ongoing antigenic stimuli with the release of chemical mediators responsible for short term bronchospasm and cytokines responsible for the ongoing inflammatory process. Other insults can apparently result in very similar immunological events in asthmatics, particularly viral infections and a similar process can be initiated in children without asthma, including those with chronic bacterial infections of the lungs. There are differences in the bronchial hyperreactivity of asthma and other diseases which suggest that in the asthmatic the mast cell is either different structurally or functionally and this renders the patient susceptible to exercise induced asthma in addition to the bronchial hyperreactivity to chemical mediators common to a number of diseases with hyperreactivity. There is good evidence of direct genetic control of atopy and the large majority of children with asthma are atopic but there is no direct genetic link between atopy and asthma and twin studies strongly suggest the existence of a 'permissive' asthma gene which will allow the disease to develop if there is an appropriate external trigger. The only drugs which have been shown to significantly reduce bronchial reactivity are the corticosteroids with a lesser effect noted for sodium cromoglycate and nedocromil. Inhaled corticosteroids can reverse the immunologic inflammatory process and reduce bronchial reactivity, sometimes to normal levels, but on stopping treatment the patient reverts back to the asthmatic state. At the present time it appears that controlled longterm inhaled corticosteroid therapy is the most rational treatment for significant perennial childhood asthma. PMID- 8480546 TI - A specific feedback by anti-IgE autoantibodies on the cytokine network in allergy. AB - During recent years we have shown that anti-IgE antibodies can have different biological functions. Depending on their epitope specificity they can be anaphylactogenic or not, they interfere with IgE binding to its receptor or not, and they enhance or inhibit IgE synthesis. Therefore we propose a theoretical model implying that anti-IgE autoantibodies are specific feed back molecules that neutralize IgE induced by the cytokine network. In the normal individual this system would be beneficial, where as the atopic individual, due to differences in its B cell repertoire, will produce the wrong type of anti-IgE antibody. The wrong type of anti-IgE antibody may even aggravate the disease as some of these autoantibodies may induce IgE synthesis or trigger effector cells that in turn generate a Th2 like cytokine pattern. PMID- 8480547 TI - Immuno-allergologic aspects of childhood asthma. AB - Asthma has a major impact on the health of children. Airway inflammation and bronchial hyperresponsiveness of variable severity have presently come to be considered underlying the pathogenesis and pathophysiology of the condition. Atopy in infancy seems to predict the severity of bronchial hyperresponsiveness in later childhood. Genetic predisposition, allergen exposure and contributory factors combine to set the clinical picture. Early sensitization to ingested or inhaled allergens accelerates development of allergic asthma. In children, the activity of inflammation can be assessed by estimation of indirect markers. PMID- 8480548 TI - Mechanisms of airways inflammation which may be amenable to prophylaxis. AB - The presence of mucosal inflammation in the lower airways of atopic asthmatics and to a milder degree of atopic nonasthmatics suffering from rhinitis points to atopy and allergen exposure as risk factors for lower airways disease. The study of mechanisms which regulate the degree of inflammation should enable the understanding of why some individuals suffer from rhinitis alone whereas others go on to develop bronchial disease. This information should enable the development of prophylactic strategies to prevent atopy from expressing itself in the lower airways. PMID- 8480549 TI - The risks and benefits of inhaled antiinflammatory therapy in children. PMID- 8480550 TI - The use of inhaled steroids in young children. AB - There are apparently irreversible inflammatory changes in the airways of young adults with chronic asthma so a strong case can be made for starting anti inflammatory treatment early. Corticosteroids have potent and diverse anti inflammatory activity. High efficacy is established in school age children. Trials in pre-school children and infants have given more mixed results perhaps because of problems with administration. No clinically important systemic effects have been observed in children taking conventional doses of inhaled steroids. PMID- 8480551 TI - Comparison of different inhalation schedules to control childhood asthma. AB - In a double-blind, placebo-controlled study control of asthma was assessed by diary symptom cards, peak-flow measurements and lung function within 3 treatment groups over a 6 months period. 36 children (25 boys, 11 girls 5.5 to 13.2 years of age) with exogen allergic, perennial asthma inhaled either beclomethasone dipropionate (BDP) with salbutamol (S) or disodium cromoglycate (DNCG) with S or a placebo preparation with S from metered dose inhalers (MDI) through a large spaced auxiliary device (Volumatic). At entry, after 2 and 4 months lung function tests were performed evaluating changes in the degree of pulmonary hyperinflation, bronchial obstruction, and bronchial hyperreactivity (BHR). Daily PF measurements showing wide variations (up to 10-12%) were insensitive to indicate any significant changes. In contrast evaluation of symptom diaries presented dramatic improvement during the first 3 months of the study. In addition, the DNCG group showed significant improvement of BHR (p = 0.02). Moreover, the majority of patients on regular therapy with salbutamol and placebo showed an increase of airway resistance. It is concluded that even in mild childhood asthma, for optimal control a combination of a beta 2-stimulant as bronchodilator and DNCG or BDP as protector should be applied. PMID- 8480552 TI - Psychosomatic symptoms in asthmatic children and adolescents. AB - In order to identify different patterns of association between physical and psychical symptoms in childhood asthma 102 children have been investigated. Somatic investigations included clinical examination, whole-body plethysmography, total IgE and RAST of specific allergens such as pollens, mites and animals. Psychosocial assessment comprised a semi-structured interview and questionnaires (Achenbach, CBCL and Olson, FACES II). There were typical psychosocial patterns in function of aetiopathogenetic groups. The infection-induced asthma was accompanied by high anxiety and here the most school problems were found. Children with seasonal asthma were psychologically healthy whereas those with perennial asthma showed important psycho-vegetative difficulties secondary to chronic somatic disease. Atypical asthma was found to be most often associated with real psychiatric symptoms. We concluded that psychosocial findings are heterogeneous and should be interpreted in relation to somatic manifestations. PMID- 8480554 TI - Assessment of functional abnormalities in infants and children with lung disease. AB - Lung function testing in infants and children has to cover a wide palette of various investigational procedures and the fact that babies can predominantly only be tested asleep and young children may not cooperate accurately must be taken into account. There is still a life-span between 2 and 5 years in which lung function testing is impossible. Different techniques for infants lung function testing (spirometry, squeeze-jacket method, forced oscillation technique, occlusion technique, whole-body infant-plethysmography, multibreath nitrogen washout (MBNW), interruption technique), which helps already in early childhood to evaluate objectively clinical findings in infants after infant respiratory distress syndrome (iRDS) with/or without hyaline membrane disease (HMD), developing or not developing broncho-pulmonary dysplasia (BPD), wheezy bronchitis or cystic fibrosis (CF) are available. Lung function techniques in children include spirometry, whole-body plethysmography, multibreath nitrogen washout (MBNW), interruption technique, bronchial challenge tests, exercise testing. PMID- 8480553 TI - Consequences of unbalanced protease in the lung: protease involvement in destruction and local defense mechanisms of the lung. AB - Complex mechanisms regulate sequestration, retention and migration of neutrophils in the lung. Neutrophils can migrate into the lung without producing significant damage under some circumstances, whereas at other times great structural alteration occurs. A potential explanation lies in the phenomenon of priming, a state of altered responsivity of neutrophils. A wide variety of molecules are able to induce this higher degree of responsiveness including PAF, TNF, GM-CSF, and IL-1. Enhanced cellular responses include secretion, adhesion and synthetic function. Unprimed neutrophils can migrate through lung tissues, secreting but little of their contents, in the context of "normal" inflammatory response. On the other hand neutrophils primed before the emigration phase, injury to the tissue they are migrating through would be likely by virtue of releasing toxic mediators. One of these mediators is neutrophil elastase, a potent protease. It is the purpose of this review to highlight the duality function of neutrophils as (i) one of the bodies highly effective host defense weapons and (ii) mediator of destruction and host defense impairment in the lung by releasing mediators such as neutrophil elastase. PMID- 8480555 TI - A new method for assessing flow-volume measurements by means of a simple isoflow electronic pocket device (IfloPen). AB - The IfloPen is a new device for measuring isoflows featuring specific information about the effort-independent part of the flow-volume curve. Whereas the recording of the latter normally requires expensive equipment, the IfloPen is a handy, portable and simple device. In addition, the isoflow technique requires minimal cooperation. Significant correlations have been found between the isoflow-points measured with the IfloPen and PF, MEF50, MEF25 and FEV1 (p < 0.001). The IfloPen showed better correlations with spirometric lung function data than with the Peak flow-Meter. Even experimentally induced bronchial obstruction during a bronchial challenge with carbachol can be measured functionally by the IfloPen, showing similar changes as obtained by the FEV1 and the MEF50 (p < 0.001). From a practical point of view, the IfloPen features a new device to measure more accurately bronchial obstruction (no overestimation, physiological breathing maneuver, good practicability). It can therefore be used in medical practice and is a suitable device for home monitoring. PMID- 8480556 TI - The interrupter technique--a renaissance of a non-invasive approach for lung function testing in infants and children. AB - The analysis of the postocclusional rapid oscillatory mouth pressure transients pao(t) after expiratory flow interruption during 100 ms features additional information to the conventional interrupter technique. The analysis focuses on the sudden oscillatory rise in pressure after flow interruption and the following damped oscillation. By calculating the first derivative of pao(t) ( = change in pressure), the frequency omega 0 and damping characteristic d of the pressure swings reflecting the inertive and elastic properties of the thoracopulmonary system can be computed. The interrelationship between omega 0 respectively d and different sizes of lung volume respectively characteristics of airway mechanics (airway resistance (Raw) and/or maximal expiratory flow at 50% vital capacity (MEF50)) was evaluated in 5 healthy adult subjects (28-37 y) and 10 healthy children (7-14 y). The measured frequency was statistically significantly related to lung volume (p < 0.05) and varied between 66 Hz in healthy adults and 91 Hz in children. The damping factor d increased with increasing airway resistance (n.s.) and decreasing MEF50 (p < 0.005). These findings add further arguments to the conjecture previously intimated that development of the viscoelastic properties of the lung are defined by characteristics of airway mechanics in close relationship to lung growth. In consequence, alterations in mechanical properties observed in diseased lungs have functionally closely be evaluated in relation to actual lung volumes (pulmonary hyperinflation, restrictive lung disease). PMID- 8480557 TI - The lung clearance index (LCI) as an estimate of ventilation inequalities in patients with cystic fibrosis. AB - Assessment of respiratory function is indispensable for provision and control of respiratory care in infants and children with lung disease. Based on plethysmographic measurements and the multibreath nitrogen washout (MBNW) distinction of patients with cystic fibrosis (CF) into different functional groups revealed that the mixed type (TGV > 130 % pred. and Raw > 130 % pred.) has to be considered as worst: highest degree of trapped gases (TG) and ventilation inequalities and consequently most impeded gas exchange. Best predictor in patients with abnormal gas exchange are the degree of bronchial obstruction (Raw) and the amount (TG). Vital capacity (VC) as overall estimate of lung function is best predicted by TG, FEV1 and MEF50. The major merit of the MBNW technique is the possibility to have the amount of TG estimated. Based on the present the calculation of the LCI adds no further information of sufficient clinical importance, remaining the question open, whether the assessment of the so called "moment ratios" from the entire washout curve would feature a better estimate of disturbed lung physiology. PMID- 8480558 TI - Prevalence of childhood asthma: facts, tendencies and interpretations. AB - Questionnaire surveys are an appropriate instrument to assess epidemiologic data on respiratory ill health, to analyse influences of environmental factors on respiratory morbidity and to evaluate treatment strategies. To investigate the prevalence rates of asthma and symptoms suggestive of asthma we performed population surveys in Swiss school children. Special attention is drawn to particular aspects such as atypical symptoms, underdiagnosis and undertreatment of asthma. PMID- 8480559 TI - Family-centered birthing: a niche for family physicians. PMID- 8480560 TI - Integrating mental health into family practice. PMID- 8480561 TI - Erythema nodosum and Hansen's disease. PMID- 8480562 TI - Aminoglycosides for infections in the elderly. PMID- 8480563 TI - Nonulcer dyspepsia: current approaches to diagnosis and management. AB - Many patients with dyspepsia do not have peptic ulceration or other organic disease that explains their symptoms. The etiology of nonulcer dyspepsia is not established, and its treatment remains empiric. A careful clinical evaluation can usually rule out other disorders, such as gastroesophageal reflux disease and irritable bowel syndrome, and can identify patients who require immediate investigation and those who can safely receive empiric therapy with antacids or a histamine H2-receptor antagonist. If diagnostic investigation is indicated, endoscopy is the procedure of choice. The physician can then classify patients with documented nonulcer dyspepsia on the basis of symptoms, which may guide therapy. Many patients with nonulcer dyspepsia respond to reassurance, explanation, dietary modifications and avoidance of precipitating factors. PMID- 8480564 TI - Management of cataract in adults. Agency for Health Care Policy and Research. PMID- 8480565 TI - Pyogenic hepatic abscess. AB - Pyogenic hepatic abscess is a rare condition associated with severe sequelae. The diagnosis may be obvious in patients with fever and leukocytosis who are clearly predisposed to this infectious complication. In patients without known risk factors, diagnosis and treatment are often delayed, usually until numerous health care resources have been consulted. The evaluation of occult hepatic abscess may be improved by a history directed at identifying predisposing conditions, by an appropriate physical examination and by the use of computed tomographic scanning. The standard treatment for pyogenic hepatic abscess is percutaneous or open drainage, accompanied by broad-spectrum antibiotic therapy. PMID- 8480566 TI - Common dermatoses in the elderly. AB - Common dermatoses in the elderly include xerosis, pruritus, contact dermatitis, acne rosacea, stasis dermatitis, bullous pemphigoid and herpes zoster. Physicians must be able to recognize these pathologic changes superimposed on the intrinsic and extrinsic effects of aging. Diagnosis is dependent on clinical appearance and supportive laboratory studies. Management is based on correct diagnosis. PMID- 8480567 TI - Cluster headache. AB - Cluster headache is a rare condition that predominantly affects older men. The diagnosis is based on the history and clinical characteristics, which are distinctive. The headache is always unilateral, excruciating and, most uniquely, occurs in timed attacks, called "clusters." The etiology is unknown, but disturbances in the hippocampal areas controlling circadian rhythm may contribute to cluster headache. Various treatments to relieve individual attacks and to shorten active cluster periods have been used, including systemic corticosteroids, lithium, ergotamine and calcium channel blockers. Patient education and individualized treatment are important elements of the management plan. PMID- 8480568 TI - The rational management of labor. AB - Some practices and procedures that are common during the management of childbirth lack proof of efficacy, and some have adverse effects. The practice of withholding food and liquids and using intravenous fluids during labor may pose risks such as fluid overload, and maternal and fetal hyperglycemia. Enemas should be reserved for women with painful constipation. Evidence does not support the value of shaving the perineal area. Nonpharmacologic measures to control pain during labor are safe and moderately effective. Pharmacologic methods of analgesia and anesthesia provide good pain relief but pose significant risks. Continuous electronic fetal monitoring should be considered a diagnostic procedure, not a screening procedure. Amniotomy may shorten labor but can result in abnormally high uterine forces, infection, umbilical cord prolapse and fetal laceration. Position changes and alternative birth positions promote greater comfort and efficiency during labor. Finally, episiotomy has not been shown to reduce severe lacerations or prevent pelvic relaxation, and use of this procedure should be limited. PMID- 8480569 TI - AMA issues diagnostic and treatment guidelines on child sexual abuse. PMID- 8480570 TI - Ultrasound guide wire-directed stent deployment. AB - A new mechanically rotated 20 MHz intravascular ultrasound guide wire (0.032 inch) with a transducer core was placed through the central lumen of a peripheral arterial balloon-expandable stent. Using an anesthetized canine model, 11 stents were then deployed into the iliac or femoral arteries. Eight stents were successfully deployed with proper position and full stent expansion documented by ultrasound imaging. Four of the stents were overlapping and the double row of stent struts at the region of overlap was easily seen. Three stents were unsuccessfully deployed because of undersizing, as clearly documented by ultrasound imaging showing stent strut recoil. As a result, the procedure was modified by performing ultrasound measurements of arterial dimensions before stent selection. There were no complications attributed to the ultrasound guide wire. This study demonstrates an effective combination of diagnostic and therapeutic devices that may allow more precise placement of intravascular stents. PMID- 8480571 TI - Serial angiographic observations after successful directional coronary atherectomy. AB - This study focuses on the early and late angiographic evolution observed in 82 patients with coronary artery disease who were successfully treated by directional coronary atherectomy (DCA) without adjunctive balloon angioplasty. Qualitative inspections and quantitative measurements were obtained from a selected angled-view projection in the following conditions: (1) before treatment; (2) immediately after treatment; (3) the day after atherectomy; (4) 1 month after; and (5) 6 months after. The appearance of the treated segment 24 hours after the procedure did not differ in 79 patients from that observed immediately after DCA; silent total occlusion occurred in two patients, and one had an aneurysm at the site of resection (all three patients were excluded from the analysis). At the 1-month study restenosis developed in 3 (3.6%) patients; the remaining 76 had identical appearances, with no evidence of renarrowing of the lumen. However, from 1 to 6 months after the procedure restenosis developed in 35 of the remaining 76 (46%) patients, and 41 patients were free of restenosis and symptoms. These findings, which show that early elastic recoil does not occur after successful DCA, are different from the changes observed after balloon angioplasty. At the 1-month observation restenosis is an infrequent but possible phenomenon (3.8%). From this point the healing of the arterial wall leads to no or mild renarrowing (late success); an exaggerated proliferative response produces restenosis. PMID- 8480572 TI - Preprocedural anticoagulation does not reduce angioplasty heparin requirements. AB - To determine whether continuous preprocedural heparin influences the need for anticoagulation during percutaneous transluminal coronary angioplasty (PTCA), we compared heparin requirements in patients therapeutically anticoagulated after continuous heparinization for > or = 12 hours with patients not pretreated with heparin (controls). A Hemochron device was used to monitor the activated clotting time (ACT) values during the procedure. An ACT > or = 300 seconds was used as a measure of optimal anticoagulation. Patients pretreated with heparin had significantly higher preprocedural ACT measurements (163 +/- 31.5 vs 126 +/- 13 seconds, p < 0.001) and partial thromboplastin time (PTT) measurements (46 +/- 15 vs 25 +/- 3 seconds, p < 0.001) than controls. While the amount of heparin needed to achieve an initial ACT > 300 seconds was slightly greater in control patients (10,682 +/- 1,852 vs 9,269 +/- 2,993 units, p < 0.001), the total heparin required to maintain an ACT > 300 seconds throughout the procedure was similar between the two groups (11,551 +/- 3,181 units vs 12,136 +/- 2,575 units, p = NS). Thus preprocedural anticoagulation does not significantly reduce total heparin requirements, and these patients should receive the same initial heparin regimen as patients not pretreated with intravenous heparin. PMID- 8480573 TI - Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarction. AB - The mechanism of adverse effects of calcium channel blockade on cardiac performance and survival in patients with cardiac dysfunction after myocardial infarction is controversial. To test whether left ventricular dilatation and remodeling, as predictors of long-term survival and cardiac performance, are important, rats with healed infarcts received a vasodilating calcium channel blocker (anipamil) or placebo. After 8 weeks the mortality rate (total population n = 111) was 35% with calcium channel blockade and 4% with placebo in rats with infarction (p < 0.001). In survivors with large infarctions (44% +/- 12% of left ventricle, n = 9), calcium channel blockade did not aggravate left ventricular dysfunction and decreased chamber stiffness, but increased left ventricular volume (1.55 +/- 0.13 ml/kg, p = 0.03 vs placebo: 1.16 +/- 0.11 ml/kg; n = 11) (passive pressure-volume relationship) at persistently elevated volume/mass ratio. Thus this study shows for the first time that aggravation of left ventricular dilatation and remodeling is one important mechanism by which calcium channel blockade may reduce survival in the presence of ventricular dysfunction after myocardial infarction. PMID- 8480574 TI - Tedisamil (KC 8857) is a new specific bradycardic drug: does it also influence myocardial contractility? Analysis by the conductance (volume) technique in coronary artery disease. AB - To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope Emax fell by 14% at rest (13 patients) and by 10% during tachycardia (6/13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil (p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QTc duration increased by 14% (p < 0.05), filling pressure and dp/dtmin remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease. PMID- 8480575 TI - Prevalence and functional significance of transient ST-segment depression during daily life activity: comparisons of ambulatory ECG with stress redistribution thallium 201 single-photon emission computed tomographic imaging. AB - To assess the prevalence and functional significance of ischemic ambulatory ECG responses, we prospectively performed ambulatory ECG monitoring in 244 patients (mean age 61 +/- 10 years) referred for stress redistribution thallium 201 myocardial perfusion scintigraphy. The prevalence of ST-segment depression during ambulatory ECG was 33% among patients with a positive exercise ECG, but prevalence varied in selected patient subgroups. Among three groups with coronary artery disease (CAD), the group with ambulatory ECG ischemia (group 1) had a greater frequency of ischemic thallium responses (p = 0.07), a greater median number of reversible thallium defects (p < 0.05), and a greater summed thallium "reversibility" score (p < 0.05) than did the group with a positive exercise ECG but negative ambulatory ECG response (group 2) or that with negative exercise and ambulatory ECG responses (group 3). Exercise ST depression in group 1 versus group 2 was significantly greater (p = 0.002), occurred at a lower heart rate threshold (p = 0.002), and lasted longer after exercise (p = 0.001). Notably, one third of group 1 patients also manifested evidence of transient ischemic dilation of the left ventricle after exercise (p < 0.01 vs groups 2 and 3), a sign of severe ischemia. However, although functionally less "sick" than group 1 patients, 66% of group 2 patients and 50% of group 3 patients still had an ischemic thallium response, which was sometimes severe. Thus transient ischemia during ambulatory ECG monitoring identifies a functionally sicker cohort of patients with CAD and occurs in approximately one third of CAD patients with positive results of exercise tests. A negative ambulatory ECG response, however, does not exclude functionally significant disease among CAD patients. These results imply that caution should be applied in the interpretation of a negative ambulatory ECG response for the purpose of patient risk stratification. PMID- 8480576 TI - Dobutamine stress echocardiography: prevalence of a nonischemic response in a low risk population. AB - The problems of population referral bias in the calculation of specificity in diagnostic testing for coronary artery disease have been previously described. Previous studies investigating the sensitivity and specificity of dobutamine stress echocardiography (DSE) have been subject to pretest and posttest referral biases, largely as a result of the requirement for coronary arteriography. This study determines the normalcy rate for DSE by examining a population at statistically low risk for coronary artery disease. The probability of significant coronary artery disease was determined for 828 consecutive patients referred for DSE at the University of Michigan, and groups were identified with < 10% and < 5% probability of disease. Four of 72 patients (5.6%) with a normal baseline echocardiogram and a probability of coronary artery disease of < 10%, and three of 38 (7.9%) with a probability of < 5% were found to have an abnormal DSE, yielding normalcy rates of 94.4% and 92.1%, respectively. The area of abnormality involved the posterior circulation in three of four patients (75%). This study demonstrates that DSE has a normalcy rate of 92% to 94% and is an accurate test for excluding the presence of significant coronary artery disease. PMID- 8480577 TI - Catheter ablation with radiofrequency current of ventricular tachycardia originating from the right ventricle. AB - Catheter ablation of ventricular tachycardia (VT) with radiofrequency current would be safer than the conventional ablation with direct current shocks. Seven patients who had eight morphologically distinct symptomatic monomorphic VTs underwent catheter ablation with radiofrequency current. The mean age +/- SD was 52 +/- 16 years, and the mean cycle length of the clinical VT was 298 +/- 36 milliseconds. Sustained VT was induced by programmed stimulation with or without isoproterenol in four patients and developed during the infusion of isoproterenol alone in two patients. Of these, four VTs were entrained with rapid pacing. The ablation was attempted at the site of earliest activation through the distal electrode and the external patch electrode on the back during VT in seven episodes in six patients. In the other patient it was applied during sinus rhythm. Energy was 40 to 50 W in the first case and 30 to 40 W in the others, and was given for 30 seconds. All VTs were terminated within 6 seconds, 3.6 +/- 0.8 seconds after the application of the radiofrequency current. Additional current was given to one to four predetermined sites by mapping. The mean number of applications was 4.0 +/- 1.3 sites. Except in the first patient, VT was eliminated successfully and VT was not induced by programmed stimulation, by the administration of isoproterenol, or by treadmill exercise testing. VT did not recur during the follow-up period of 6.8 +/- 1.1 months. PMID- 8480578 TI - Increasing catheter ablation lesion size by simultaneous application of radiofrequency current to two adjacent sites. AB - Treatment of ventricular tachycardia by radiofrequency current application can be difficult, partly because of the larger size of the reentry circuit in relation to the lesion generated. Larger lesions than those currently achieved with single radiofrequency applications are desirable. This study evaluated simultaneous radiofrequency application to two adjacent electrodes to determine the effects of inter-electrode distance and configuration (bipolar serial vs parallel) on lesion size and tissue temperature. Two 6F electrodes were placed, with the tips facing each other, on bovine myocardium in a saline bath at 37 degrees C. Radiofrequency current was applied to a single electrode, or simultaneously to two electrodes connected either in series or in parallel. Tissue temperature, power, and lesion size were measured. Lesions produced by simultaneous radiofrequency delivery to both electrodes were more than twice the size of those produced by a single electrode alone (> 100 mm3 vs 33.2 mm3, p < 0.01). Temperatures between electrodes were greater than those temperatures at the same distances from a single electrode (p < 0.001). The size of the lesions increased as inter electrode distance decreased below 3.5 mm (p < 0.030) because of the increasing depth of the lesion between the electrodes. Two electrodes placed in a bipolar as opposed to a parallel configuration were most efficient, as this configuration produced greater lesion sizes for a given level of power delivery (p < 0.0001). The bipolar lesion size decreased by > 50% if one electrode was not in contact with the tissue (p < 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480579 TI - Effects of diltiazem on concealed atrioventricular nodal conduction in relation to ventricular response during atrial fibrillation in anesthetized dogs. AB - By means of a new quantitative index for concealed conduction, we evaluated the effects of diltiazem on atrioventricular (AV) node concealment and correlated this index with the variability of the ventricular response during atrial fibrillation in 16 anesthetized mongrel dogs. After determination of the atrial effective refractory period (ERP), AV nodal ERP (AVNERP), concealment zone, and concealment index (AVNERP of blocked atrial extrasystole/AVNERP of conducted atrial extrasystole), the R-R intervals during atrial fibrillation induced by electrical stimulation were measured. Both low (0.1 mg/kg) and medium (0.2 to 0.4 mg/kg) doses of diltiazem prolonged the AVNERP and increased the mean R-R interval during atrial fibrillation. Only medium doses of diltiazem increased the degree of concealed conduction in the AV node and accentuated the variability of R-R intervals. There was a good positive correlation between the variability of the ventricular response during atrial fibrillation and the concealment index. In conclusion, medium doses of diltiazem are more effective in reducing heart rate during atrial fibrillation than a low dose. However, medium doses also increase the degree of concealed conduction in the AV node and enhance the irregularity of the ventricular response during atrial fibrillation. Measurement of the concealment index is useful for quantitating the degree of concealed conduction in the AV node, which is actually an important determinant of the ventricular response during atrial fibrillation. PMID- 8480580 TI - Longitudinal study in 18 cases of fetal supraventricular tachycardia: Doppler echocardiographic findings and pathophysiologic implications. AB - A longitudinal study was performed in nine nonhydropic and nine hydropic fetuses with supraventricular tachycardia (SVT). First, because of a lack of reference methods in utero, the validity of spatial (length and area) and temporal parameters for semiquantitative grading of atrioventricular (AV) valve regurgitation by color Doppler flow mapping and M-Q mode imaging was evaluated by a longitudinal intraindividual study before and after drug-induced cardioversion to sinus rhythm and by correlation with the severity of hydrops and the time required for complete remission of hydrops. Second, with the demonstration of AV valve incompetence and changes in venous blood flow velocity wave forms, new data were collected concerning chronic SVT in the fetus. AV valve incompetence occurred in eight fetuses: during SVT only in three severely hydropic fetuses, during sinus rhythm in one nonhydropic fetus, and in seven hydropic fetuses including those previously mentioned, where AV incompetence outlasted tachycardia. The length and area of the regurgitant jet as imaged by color Doppler flow mapping and the temporal duration of regurgitation in relation to the systolic phase as measured by M-Q mode continuously diminished intraindividually but with great interindividual differences in the time span required for complete remission, which ranged from 5 to 42 days. Pulsed-wave Doppler studies of blood flow in the inferior vena cava and left hepatic vein demonstrated normal biphasic forward flow with a systolic and a diastolic surge during sinus rhythm in all fetuses and in two instances also during SVT of 190 and 195 beats/min, respectively. In all cases a pulsatile reversal of blood flow with systolic forward flow and diastolic reverse flow was observed during tachycardia greater than 220 beats/min. Thus the presence of functional AV valve incompetence as a result of annular enlargement seems to be a sign of SVT-induced "cardiomyopathy" during fetal life. AV valve incompetence during SVT was always associated with extremely severe hydrops and seemed to indicate the most severe degree of ventricular dysfunction, which could influence the selection of antiarrhythmic drugs. After termination of SVT, severe AV valve insufficiencies also occurred in other cases of hydrops, probably because of the markedly increased diastolic filling distending the already enlarged annular ring. The observed great interindividual differences in time required for disappearance of AV valve incompetence and hydrops could be explained by a different state of progression of tachycardia-induced "cardiomyopathy" at the time of drug-induced cardioversion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8480581 TI - Hemodynamic determinants of exercise capacity in chronic atrial fibrillation. AB - To evaluate the response of patients with chronic atrial fibrillation (AF) to exercise, 79 male patients (mean age 64 +/- 1 years) with AF underwent resting two-dimensional and M-mode echocardiography and symptom-limited treadmill testing with ventilatory gas exchange analysis. Patients were classified by underlying disease into five subgroups: no underlying disease (LONE: n = 17), hypertension (HT: n = 11), ischemic heart disease (n = 13), cardiomyopathy or history of congestive heart failure (CHF: n = 26), and valvular disease (n = 12). A higher maximal heart rate than expected for age was observed (175 vs 157 beats/min), which was most notable in the LONE and HT subgroups. Maximal oxygen uptake (VO2 max) was lower than expected for age in all groups. Patients with CHF had a lower resting ejection fraction than all other patients (p < 0.001), a lower VO2 max, and a lower maximal heart rate than LONE and HT patients (p < 0.001). Stepwise regression analysis demonstrated that echocardiographic measurements at rest were poor predictors of VO2 max and VO2 at the ventilatory threshold. Among clinical, morphologic, and exercise variables, maximal systolic blood pressure accounted for the greatest variance in exercise capacity, but it explained only 35%. In patients with AF the higher than predicted maximal heart rates may be a compensatory mechanism for maintaining exercise capacity after the loss of normal atrial function. However, even in the absence of underlying disease, it does not appear to compensate fully for a compromised exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480582 TI - Increased risk of progressive hemodynamic deterioration in advanced heart failure patients requiring permanent pacemakers. AB - To determine the influence of long-term permanent pacing systems on survival in patients with severe left ventricular dysfunction, data from 557 consecutive patients hospitalized with advanced heart failure for cardiac transplant evaluation and discharged on medical therapy were reviewed. Permanent pacemakers were identified in 42 (8%) patients. One-year actuarial risk of death from heart failure or urgent transplantation in paced patients was higher (49%) than that of a control group, matched for the severity of heart failure (15%, p = 0.003). Sudden death did not differ between paced patients and controls. PMID- 8480583 TI - On-line estimation of stroke volume by means of echocardiographic automated border detection in the canine left ventricle. AB - Echocardiographic automated border detection (ABD) is a new on-line technique that can determine the interface between blood and myocardial tissue and calculate left ventricular (LV) cavity area in real time. The objective of this study was to determine whether ABD measurements of the LV cavity area could be used to estimate LV stroke volume at basal conditions and during large changes in LV stroke volume induced by inferior vena caval occlusions in an open-chest canine model. Seven dogs had LV stroke volume measured by electromagnetic flow from the ascending aorta with epicardial recordings of ABD echocardiographic area at the midventricular short-axis level. Simultaneous beats of stroke volume were recorded along with ABD echo area during baseline apnea and during IVC occlusions. Neither ABD echo stroke area nor stroke volume varied significantly during apnea baseline. Changes in stroke area were closely correlated with changes in stroke volume for 540 matched beats from 24 IVC occlusions: R = 0.93, standard error of the estimate = 5%, y = 0.92x + 0.4 (p < 0.001). Echocardiographic ABD appears to be a promising new on-line method of determining rapid alterations in LV stroke volume; it also has potential applications to multiple investigational and clinical settings. PMID- 8480584 TI - 31P MR spectroscopy in hypertrophic cardiomyopathy: comparison with Tl-201 myocardial perfusion imaging. AB - Abnormal phosphate metabolism of the myocardium was evaluated in patients with hypertrophic cardiomyopathy (HCM) using 31P magnetic resonance (MR) spectroscopy. The results were compared with those from left ventricular function and thallium 201 (Tl-201) perfusion scintigraphy. Six normal volunteers and 19 patients with HCM were studied with a 1.5 T MR system. The spectra were localized to the myocardium using volume selection with the depth-resolved surface coil spectroscopy (DRESS) technique. Peak areas of 2,3-diphosphoglycerate (DPG), phosphodiesters (PDE), phosphocreatine (PCr), and beta-ATP were determined by fitting Gaussian functions to the phased spectra. The peak areas were corrected for contamination of blood adenosine triphosphate (ATP) and PDE. The corrected PCr/beta-ATP ratio in patients (1.07 +/- 0.10, mean +/- SE) was significantly lower compared with that in normal volunteers (1.71 +/- 0.13, p < .01). The PCr/beta-ATP ratio showed an abnormal decrease (< mean -2 SD of the controls) in 11 (58%) of 19 patients. The averaged PCr/beta-ATP ratio in 15 patients with normal left ventricular ejection fraction (LVEF) was 1.14 +/- 0.10, significantly lower than in healthy subjects. By contrast, the corrected PDE/PCr ratio in HCM did not differ significantly compared with that in healthy subjects (0.46 +/- 0.09 vs 0.36 +/- 0.09). The PDE/PCr ratio was abnormally elevated (> mean + 2 SD of the controls) in only four (21%) of the patients. On Tl-201 myocardial single photon emission computed tomography (SPECT) imaging, the perfusion of the left ventricular wall looked normal in 6 and abnormal in 5 of 11 HCM patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480585 TI - Coronary vasodilating action of dobutamine in patients with idiopathic dilated cardiomyopathy. AB - To assess the coronary hemodynamic effects of dobutamine in patients with idiopathic dilated cardiomyopathy, dobutamine was infused at the incremental infusion rates of 25, 50, 100, and 200 micrograms/min into the left main coronary artery of nine patients undergoing cardiac catheterization. In response to dobutamine infusion, systemic hemodynamic effects were dose related. At the highest infusion rate cardiac index and left ventricular peak positive rate of rise in ventricular pressure increased from 2.33 +/- 0.54 to 2.97 +/- 0.65 L/min/m (p = 0.001) and from 690 +/- 177 to 1157 +/- 275 mm Hg/sec (p = 0.001), respectively. Left ventricular end-diastolic pressure decreased from 17 +/- 8 to 8 +/- 7 mm Hg (p = 0.001) and a trend toward decrease in left ventricular wall stress was observed (from 166 +/- 75 to 148 +/- 66 gm/cm2, not significant). Heart rate and mean arterial pressure remained unchanged. The coronary hemodynamic response to dobutamine infusion was also dose related. At the highest infusion rate coronary sinus blood flow increased from 133 +/- 35 to 179 +/- 47 ml/min (p < 0.01) and was associated with an increase in coronary oxygen blood content from 4.5 +/- 0.6 to 7.8 +/- 1.7 ml per 100 ml (p < 0.01) whereas myocardial oxygen consumption remained unchanged. During dobutamine infusion norepinephrine decreased in the femoral artery and in the coronary sinus from 1.03 +/- 0.34 to 0.641 +/- 0.179 ng/ml (p < 0.05) and from 1.76 +/- 0.98 to 1.38 +/- 0.65 ng/ml (p < 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480586 TI - Variation in left ventricular regional wall stress with cine magnetic resonance imaging: normal subjects versus dilated cardiomyopathy. AB - We measured the variation of end-systolic wall stress and its relation to regional ejection fraction in short-axis planes through the left ventricle in normal subjects and in patients with dilated cardiomyopathy (DCM) by cine magnetic resonance imaging. There was a gradual increase in end-systolic wall stress but a gradual decrease in ejection fraction from apex to base in normal subjects (14 +/- 6 to 52 +/- 15 kdyne/cm2, 78% +/- 12% to 62% +/- 8%) and in patients with DCM (49 +/- 28 to 130 +/- 30 kdyne/cm2, 40 +/- 18 to 23% +/- 9%). The end-systolic wall stress in patients with DCM was higher than in normal subjects at every level (p < 0.01). We conclude that there is a variation in end systolic wall stress in both normal subjects and patients with DCM with regional ejection fraction inversely related to regional end-systolic wall stress. PMID- 8480587 TI - Subepicardial myocardial lesions. AB - Subepicardial myocardial lesions are rarely seen at necropsy, and a description of them and their causes has not been reported. Over the last 13 years we have studied 22 patients with subepicardial myocardial lesions. They ranged in age from 14 to 73 years (mean 47), and 20 were men. The lesions were associated with atherosclerotic coronary artery disease in six patients, sarcoidosis in five, idiopathic dilated cardiomyopathy in four, lymphocytic myocarditis in two, and hypoplastic right and left circumflex coronary arteries in one. In four patients the cause was unclear. In the patients with atherosclerotic coronary artery disease, the subepicardial myocardial lesions were small, few in number, and located in the left ventricular posterior wall. In patients with sarcoidosis or myocarditis, the subepicardial lesions were extensive and commonly associated with transmural left and right ventricular lesions. The right ventricular half of the ventricular septum also was frequently affected. In the remaining nine patients, the subepicardial lesions were small and unassociated with transmural left ventricular lesions. Thus subepicardial myocardial lesions occur in a variety of cardiac diseases. PMID- 8480588 TI - A new model for infective endocarditis of the mitral valve in rabbits. AB - To produce an experimental model of infective endocarditis without inserting catheters into the heart, we injected a bacterial suspension into rabbits in which mitral complex lesions had been induced by electrical stimulation of the cervical vagus. Typical infective vegetations grew on the surface of the mitral valves 1 week later. The formation of vegetations was related to the timing of the inoculation. Streptococcus viridans injected just after vagal stimulation produced vegetations in 10 of 17 animals (58.8%), but the same bacteria injected 14 days after vagal stimulation did so in only 2 of 11 animals (18.2%). The incidence of infective endocarditis was significantly higher after early inoculation compared with delayed inoculation (p < 0.01). The susceptibility to infection depended on the species of bacteria injected. Both S. viridans and Pseudomonas pseudoalkaligenes injected just after vagal stimulation produced vegetations in 10 of 17 (58.8%) and 6 of 13 (46.2%) animals, respectively, but Staphylococcus epidermidis injected just after vagal stimulation did not produce vegetations in any of the 10 animals. S. viridans injected into nine normal animals never produced vegetations. These findings indicate that infective endocarditis develops after intravenous injection of bacterial suspensions alone in rabbits with mitral complex lesions. PMID- 8480589 TI - The safety of transesophageal echocardiography in the elderly. AB - The safety of transesophageal echocardiography (TEE) in elderly patients (aged > or = 70 years) and young patients (aged < or = 50 years) was compared in a retrospective study of 283 examinations in each group. A greater percentage of studies was performed in an intensive care unit in the elderly group (22%) as compared with the younger group (13%, p < 0.02). In studies performed in an intensive care unit, 39% (24/61) of patients in the elderly group and 45% (17/38) in the young group were on ventilators. Transient systemic hypotension complicating TEE was 3.5 times more frequent in the elderly (5%) as compared with the young group (1.4%, p < 0.02). Life-threatening complications associated with TEE were rare (< 0.01%) and included third-degree atrioventricular block in one patient and profound vasovagal reaction in one patient in the elderly group and myocardial ischemia in one patient in the young group. Being elderly and on a ventilator were independent predictors of the development of systemic hypotension during TEE. Overall, TEE is a low-risk procedure but is associated with a 3.5 times greater risk of systemic hypotension in elderly patients as compared with younger subjects. The benefit and risk should be assessed in all patients before TEE, particularly in the elderly. PMID- 8480590 TI - Biplane transesophageal echo-Doppler studies of atrial septal defects: quantitative evaluation and monitoring for transcatheter closure. AB - Forty-four patients with atrial septal defects, aged 7 months to 18 years (median 8.9), underwent biplane transesophageal (TEE) and transthoracic (TTE) echocardiography. The size of the defect and the shunt flow volume were measured by TEE and compared with the actual size at surgery (N = 14) or the shunt volume measured by the Fick method (N = 34), respectively. In all cases the location and morphology of the defect were clearly demonstrated by TEE; on the other hand, two patients with sinus venosus-type and multiple-type defects, respectively, and one with a small ostium primum defect did not have a complete diagnosis by TTE. The defect size determined by TEE correlated well with the surgical measurement. Similarly a significant correlation was demonstrated between the shunt volume measured by TEE and that obtained by the Fick method. In three patients transcatheter closure of the atrial septal defect by means of a clamshell device was accomplished successfully with TEE monitoring. We conclude that biplane TEE provides a better appreciation of cardiac anatomy and hemodynamic evaluation than TTE in this setting, and TEE is essential for monitoring during transcatheter closure. PMID- 8480591 TI - Left-to-right shunt through patent foramen ovale in adult patients with left sided cardiac lesions: a transesophageal echocardiographic study. AB - To define the prevalence rate of left-to-right interatrial shunt through patent foramen ovale in adults with symptomatic left-sided cardiac lesions, 56 patients were examined with transthoracic and transesophageal echocardiography and cardiac catheterization. By transesophageal echocardiography, 15 patients (group A) were found to have left-to-right interatrial shunt through patent foramen ovale, constituting a prevalence rate of 27%. In group A, transthoracic echocardiography detected the interatrial shunt in two patients, and catheterization detected it in only one. The remaining 41 patients (group B) had no shunt demonstrated by either echocardiographic or catheterization examinations. In another 44 patients (group C) with no significant left-sided cardiac lesions, no interatrial shunt could be found by transesophageal echocardiography even though some of them had a patent foramen ovale. All patients with such shunt had left atrial size > 34 mm (45.1 +/- 6.0 mm), left atrial pressure > 13 mm Hg (23.4 +/- 7.6 mm Hg), and pressure gradient between left and right atria > 10 mm Hg (19.3 +/- 5.2 mm Hg). These findings support the concept that in the presence of a patent foramen ovale any left-sided cardiac lesion increasing left atrial size and pressure may induce left-to-right interatrial shunt through this channel and that the prevalence rate is much higher than generally acknowledged. PMID- 8480592 TI - Effect of percutaneous balloon valvuloplasty on pulmonary hypertension in mitral stenosis. AB - Percutaneous mitral balloon valvuloplasty (PMBV) has been useful in decreasing mitral valve obstruction in mitral stenosis; however, the long-term effects of valvuloplasty on pulmonary artery pressure have not been extensively studied. Thirty-three patients underwent PMBV in our institution between January 1988 and December 1991. There were significant reductions in peak (19 +/- 1 to 12 +/- 1 mm Hg) and mean (10 +/- 0.7 to 6 +/- 0.4 mm Hg) mitral valve gradients estimated by Doppler techniques immediately after PMBV. The mitral valve area, as assessed by the pressure half-time method, increased from 1.06 +/- 0.05 to 1.98 +/- 0.08 cm2 (p < 0.001) after the procedure and remained significantly greater (1.68 +/- 0.11 cm2) at 17 +/- 2 months. Right ventricular systolic pressure (RVSP) was estimated in patients with tricuspid regurgitation (TR) using the modified Bernoulli equation. There was a good correlation between Doppler and catheterization for RVSP (r = 0.83 pre valvuloplasty; r = 0.87 post valvuloplasty). Right ventricular systolic pressure by Doppler was 56 +/- 4 mm Hg before valvuloplasty and 48 +/- 4 mm Hg immediately afterwards (p < 0.001). Nine patients had TR on follow-up Doppler studies with an estimated RVSP of 53 +/- 9 mm Hg (p = NS compared with pre- and post-valvuloplasty values). Six of these nine patients had moderate or severe mitral regurgitation (MR), compared with one patient without TR at follow up (p < 0.05). There appears to be a good correlation between the RVSP determined by Doppler and measured at catheterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480593 TI - The clinical spectrum of patients with aneurysms of the ascending aorta. AB - Aneurysms of the ascending aorta are often unsuspected, yet they can quickly lead to death from aortic rupture or dissection. To examine the clinical spectrum of patients with aneurysms of the ascending aorta, we searched the University of California, San Francisco (USCF) Echocardiography Data Base for all patients with aneurysms of the ascending aorta (> or = 5.0 cm in diameter) seen over a 7-year period. The echocardiograms and clinical courses of these patients were then reviewed. We identified 15 patients with aneurysms of the ascending aorta: five had aneurysms > 7.0 cm in diameter, three had aneurysms 6.0 to 6.9 cm, and seven had aneurysms 5.0 to 5.9 cm in diameter. Among the five patients < 50 years of age, four had Marfan's syndrome, and among the 10 patients > or = 50 years of age, eight had evidence of atherosclerotic vascular disease. At presentation, 13 patients had nonspecific symptoms, and two were asymptomatic. Echocardiography demonstrated that 12 patients had at least mild aortic insufficiency and that five had aortic dissections. One of the seven patients who underwent surgical resection died of an intraoperative cardiac arrest, and two of the eight patients treated medically died within 1 week of presentation. We conclude that the clinical spectrum of patients with aneurysms of the ascending aorta is wide. Because these aneurysms are often unsuspected, physicians should have a low threshold for imaging the ascending aorta in patients with Marfan's syndrome or atherosclerotic vascular disease, particularly when aortic insufficiency is present. PMID- 8480594 TI - Definition and measurement of restenosis after successful coronary angioplasty: implications for clinical trials. AB - Angiographic restenosis represents the most established measure of long-term outcome in most prospective clinical trials of coronary angioplasty (PTCA). The accuracy of assessing this endpoint is of utmost importance. The purpose of this article is to propose guidelines for the use of coronary angiography in this setting. First, the cineangiograms must be of high technical quality and performed in a high proportion of consecutive patients in follow-up under controlled study conditions that are reproducible. Second, computer-assisted quantitative coronary angiographic analysis is essential to minimize interobserver and intraobserver variability in stenosis measurement between successive studies. The following recommendations are presented for quantitative coronary angiographic analysis. Because biplane orthogonal views cannot always be performed both at baseline and at follow-up, stenosis measurement in the single plane, most severe view often constitutes the most consistent and practical approach. The edge-detection method is still much more reproducible and accurate than densitometry and should be the preferred method of analysis. Measurement of reference diameter by the interpolated method is more objective than measurement by the user-defined approach and should be used whenever possible. Finally, measurements of absolute minimum diameter and percent diameter stenosis are both important in the assessment of outcome in clinical trials. Absolute minimum diameters are independent of variations in reference diameter, and the extent of reduction in minimum diameter between the immediate postangioplasty and follow-up angiograms, when expressed in dichotomous or continuous fashion, accurately defines the extent of vessel wall hyperplasia as an endpoint. On the other hand, vessel size corresponds in general to the size of myocardium subserved, and absolute changes do not take into account this physiologic fact. Therefore defining restenosis in terms of significant reduction in percent diameter stenosis is also a useful approach because of its clinical relevance. Thus clinical restenosis requires that a successfully dilated segment (< 50% diameter stenosis) show a > or = 50% diameter stenosis at follow-up angiography with, in addition, a meaningful degree of change, that is, exceeding 2 SDs of observer variability in quantitative measurements which, in our experience, translates into > or = 15% difference between early postangioplasty and follow-up angiography measurements. PMID- 8480595 TI - Causes of congenital heart diseases: old and new modes, mechanisms, and models. PMID- 8480596 TI - Ebstein's anomaly: a long-term study of survival. AB - This study examines data regarding the survival of patients with Ebstein's malformation. Of 61 patients studied at the University of Minnesota, 31 are currently alive, with the average survival being 15 years. Several factors adversely affected survival: NYHA functional classification, hemoglobin level, right atrial pressure, symptoms during the neonatal period, and cardiac surgery. Data from a multi-institutional study collected during the past decade adds information regarding survival. Of 18,281 patients in the study, 71 (0.4%) had Ebstein's malformation. Sixteen of these were among 7235 infants, and of these seven died during the first year of life. In contrast, among 55 patients over the age of 1 year, four died, each after cardiac surgery. The data help our understanding of the course of patients with Ebstein's malformation and decisions regarding surgical treatment. PMID- 8480597 TI - Reversal of perfusion defect on resting thallium-201 emission computed tomography in stunned myocardium and coronary spasm. PMID- 8480598 TI - Internal mammary-to-coronary artery communication in a patient with occluded right coronary artery. PMID- 8480599 TI - Efficacy and safety of amiodarone in infants. PMID- 8480600 TI - Acceleration of atrioventricular conduction during corticosteroid therapy. PMID- 8480601 TI - Double atrial responses to a single ventricular premature impulse resulting from simultaneous ventriculoatrial conductions through the normal pathway and a slow paraseptal accessory pathway. PMID- 8480602 TI - Torsade de pointes induced by astemizole in a patient with prolongation of the QT interval. PMID- 8480603 TI - Atrial fibrillation after intravenous administration of gasoline. PMID- 8480604 TI - Left ventricular hypertrophy in normotensive cocaine users. PMID- 8480605 TI - Atypical presentation of papillary fibroelastoma mimicking multiple vegetations in suspected subacute bacterial endocarditis. PMID- 8480606 TI - Disappearance of a large intraaortic mass in a patient with prior systemic embolization. PMID- 8480607 TI - Complementary value of transthoracic and transesophageal echocardiography in detecting a mycotic aortic aneurysm ruptured into the right atrium. PMID- 8480608 TI - Myxoma of the mitral valve detected by transesophageal echocardiography. PMID- 8480609 TI - Single ventricle with severe pulmonary hypertension: natural survival into the third decade of life. PMID- 8480610 TI - Dilation of the ductus arteriosus by oral prostaglandin E1 derivative in cyanotic congenital heart diseases. PMID- 8480611 TI - Prospective study of bacteremia during transesophageal echocardiography. PMID- 8480612 TI - Rapid resolution of symptomatic acute pericarditis with ketorolac tromethamine: a parenteral nonsteroidal antiinflammatory agent. PMID- 8480613 TI - Impaired ventricular repolarization associated with disturbed left ventricular sympathetic function and diastolic filling in diabetes. PMID- 8480614 TI - Assessment of a coronary artery fistula to the pulmonary artery by transesophageal echocardiography. PMID- 8480615 TI - TEE in the diagnosis of intravenous leiomyomatosis extending into the right atrium. PMID- 8480616 TI - Early descriptions of aortic valve stenosis. PMID- 8480617 TI - Early descriptions of aortic regurgitation. PMID- 8480618 TI - Introduction: is hypertension a metabolic disease? PMID- 8480619 TI - Antihypertensive therapy to maximally reduce coronary risk. AB - Antihypertensive therapy as it is currently prescribed has not provided the degree of protection against coronary disease that was predicted by epidemiologic evidence. At least five steps can be taken to maximally reduce coronary risk: (1) more frequent, out-of-the-office monitoring of blood pressure, particularly during the early morning hours; (2) diligent search for other coexisting coronary risk factors; (3) vigorous use of various life-style modifications; (4) greater selectivity in the choice of antihypertensive agents, using those that may provide additional benefits for other coronary risk factors and other coexisting conditions; and (5) avoidance of coronary hypoperfusion by too great a reduction of blood pressure. PMID- 8480620 TI - Decreased peripheral blood flow in the pathogenesis of the metabolic syndrome comprising hypertension, hyperlipidemia, and hyperinsulinemia. AB - Major cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes, often cluster in the same individuals. It has been claimed that obesity, hyperinsulinemia, insulin resistance, and a deranged intracellular handling of ions have pathogenetic importance in the development of this metabolic syndrome. However, a decrease in peripheral blood flow is another factor found in all the different facets of this syndrome. An increased peripheral resistance and a rarefaction of skeletal vessels are often seen in hypertensive subjects. Also, the insulin resistance so commonly seen in hypertension may be a consequence of a decreased blood flow because insulin resistance is associated with a decreased capillarization in skeletal muscle. Furthermore, the activity of skeletal muscle lipoprotein lipase, the key enzyme involved in the removal of triglycerides from the circulation, is known to be related to skeletal muscle vascularization. Because enhanced sympathetic activity has been associated with vascular hypertrophy and rarefaction of vascularization, overactivity in this part of the autonomic nervous system may lead to structural changes that will decrease the blood flow in peripheral tissues and thereby induce the metabolic syndrome of cardiovascular risk factors, particularly in individuals who, for genetic reasons, have decreased capillarization at the onset. PMID- 8480621 TI - Pathogenesis and treatment of hypertension associated with diabetes mellitus. AB - The pathogenesis of hypertension associated with diabetes mellitus (DM) involves an interplay of hereditary and acquired mechanisms. A familial trait for essential hypertension appears to be a risk factor for the development of both hypertension and nephropathy in type I DM and coexists commonly with impaired insulin sensitivity, relative hyperinsulinemia, and dyslipidemia, which can already be detected before the appearance of hypertension, obesity, or upper abdominal redistribution of body fat. The latter finding helps explain the frequent development of hypertension as well as dyslipidemia and/or type II DM in given individuals. Obesity is an important factor promoting these complications. Type I or II DM but not uncomplicated essential hypertension is characteristically accompanied by excess body Na+. This abnormality complements a tendency toward vascular hyperreactivity and a presumably morphologic and functional vasculopathy, thereby promoting the pathogenesis of hypertension in diabetic patients. For the treatment of hypertension in diabetic patients, nonpharmacologic measures are indispensable. If drugs are needed, angiotensin converting enzyme (ACE) inhibitors and some but not all calcium antagonists are the preferred agents. Monotherapy or a combination of these drug types allows effective blood pressure control in most diabetic patients without further metabolic impairment; ACE inhibitors even tend to improve glucose control. Ketanserin may be a potential alternative, and if a diuretic is also needed, the metabolically neutral indapamide is a reasonable choice. If these agents do not allow satisfactory blood pressure highly selective beta 1-blockers or alpha 1 blockers may be introduced as a second choice. In diabetic patients with nephropathy, effective antihypertensive therapy can reduce proteinuria and slow the progression of the nephropathy; ACE inhibitors may improve diabetic proteinuria even at unchanged systemic blood pressure levels. Unless diuretics are needed for reasons other than hypertension, the treatment of diabetic patients with thiazides or loop diuretics in conventional dosage should probably be avoided until clarification of their influence on prognosis. Nevertheless, whether and to what extent other agents and nonpharmacologic measures can modify the prognosis in diabetic patients is also unclear, and the approach to antihypertensive therapy is therefore still largely empiric. PMID- 8480622 TI - Hypertension in diabetic nephropathy: prevention and treatment. AB - Hypertension is the major determinant of morbidity and mortality in diabetic patients. In type I diabetes hypertension develops in parallel with the evolution of nephropathy, whereas in type II diabetes hypertension precedes the onset of manifest diabetes mellitus by years or decades. Nephropathy is equally common in types I and II diabetes. Strong genetic determinants for nephropathy have been recognized, but it is unclear whether a genetic predisposition to hypertension and elevated sodium-lithium countertransport are involved. In epidemiologic studies hypertension is related to the risk and rate of evolution of diabetic nephropathy, retinopathy, and cardiovascular complications. The relationship appears to be causal, because antihypertensive treatment attenuates the rate of loss of glomerular filtration. In this respect angiotensin-converting enzyme inhibitors appear to be superior (renal protective action). Calcium channel blockers have been promising in experimental studies, but clinical information is currently incomplete. PMID- 8480623 TI - Reduction of left ventricular hypertrophy: how beneficial? AB - Left ventricular hypertrophy (LVH) can no longer be considered a compensatory adaptation of the heart serving to normalize the increased wall stress in hypertension. Recent studies have indicated that LVH is a powerful pressure independent risk factor for cardiovascular morbidity and mortality. The pathophysiologic sequelae of LVH are reduced ventricular filling and contractility, ventricular dysrhythmias, and diminished coronary reserve or myocardial ischemia. Left ventricular hypertrophy can be reduced by antihypertensive therapy, although not all drugs are equipotent in this regard. Recent studies have shown that such a reduction also improves the pathophysiologic sequelae of LVH, that is, ventricular filling, coronary reserve, and ventricular dysrhythmias, and maintains left ventricular pump function. Although the reversal of these pathophysiologic findings is encouraging, it remains unknown whether a reduction of LVH will ultimately reduce the excessive risk of sudden death, acute myocardial infarction, and congestive heart failure that has been associated with this disorder independent of arterial pressure. PMID- 8480624 TI - Pharmacologic profile of trandolapril, a new angiotensin-converting enzyme inhibitor. AB - Trandolapril is a newly developed angiotensin-converting enzyme (ACE) inhibitor that is rapidly hydrolyzed mainly in the liver to its biologically active metabolite trandolaprilat. The time to reach peak plasma concentrations of trandolaprilat is about 6 hours; the effective plasma half-life of accumulation at steady state is 24 hours. The active metabolite trandolaprilat has very high lipophilicity in comparison with other ACE inhibitors, which should contribute to an improved tissue penetration of the substance. The very high affinity of trandolaprilat to the ACE and the corresponding low dissociation rate are probably the two main reasons for the prolonged duration of action. The high potency of trandolaprilat in ACE inhibition is reflected by its low IC50 (concentration needed to inhibit 50% of the enzyme activity). With repeated once daily administration of trandolapril, plasma ACE activity was reduced in a dose dependent fashion, but increasing the dose beyond 2 mg did not further reduce angiotensin II levels, apparently because of the compensatory increase in plasma renin levels. Therefore trandolapril in a dose of 2 mg once a day reduces blood pressure consistently throughout the 24 hour-period after intake. Because of its particularly long half-life, trandolapril, probably more than any other drug of its class, can be considered a true, once-a-day antihypertensive drug. PMID- 8480625 TI - Influence of the nonsulfhydryl angiotensin-converting enzyme inhibitor trandolapril on lipid and carbohydrate metabolism related to exercise capacity in healthy subjects. PMID- 8480626 TI - Cardiac effects of trandolapril in hypertension. AB - Baseline echocardiography was performed on 25 patients with essential hypertension and a supine diastolic blood pressure of 95 to 114 mm Hg while receiving placebo. Once-daily trandolapril was then titrated from 1 to 4 mg. After 3 months of therapy, supine diastolic blood pressure decreased by 7.5% (p < 0.0001). Left ventricular hypertrophy regressed as evidenced by a 23.2% (p < 0.0001) decrease in left ventricular mass index at 3 months and a 12.4% (p < 0.05) reduction of relative wall thickness at 6 months. Although afterload decreased by 12.4% (p < 0.05) at 3 months, left ventricular systolic function remained unchanged, whereas left ventricular contractility, which was assessed from the load-independent relationship of end-systolic wall stress to velocity of circumferential fiber shortening, improved. Left ventricular diastolic function (E/A ratio) improved in 15 of 25 patients with low baseline values from 0.96 +/- 0.14 to 1.18 +/- 0.25 (mean +/- SD, p < 0.0002) at 3 months. We conclude that trandolapril effectively reduces left ventricular hypertrophy and improves diastolic function in patients with hypertension while systolic function is preserved. PMID- 8480627 TI - Clinical experiences with trandolapril. AB - In this article the clinical experiences with the new non-sulfhydryl angiotensin converting enzyme inhibitor trandolapril are reviewed. The drug lowers blood pressure effectively in patients with mild-to-severe hypertension including elderly and obese patients. Distinguishing features of the compound are its long plasma half-life and high degree of lipophilicity. PMID- 8480628 TI - Development and optimization of a supercritical fluid extraction method for the analysis of aflatoxin B1 in grain dust. AB - A new method for the extraction of aflatoxins from small quantities of airborne dust, using supercritical carbon dioxide, is described. The efficacy of this method is compared with a previously used liquid extraction procedure, using naturally contaminated grain dust samples. Supercritical fluid extraction (SFE) provides faster, more sensitive, and more selective extraction, compared with the liquid extraction method. The optimized SFE conditions for 0.1-1.2 g of dust in a 2.5 mL extraction chamber are: 2000 psi, 40 degrees C, 15 mL of liquid CO2, static extraction for 15 min, and 250 microL of acetonitrile added to sample in the extraction chamber. A detection limit of 1 ng aflatoxin B1 per sample is obtained using off-line HPLC analysis with UV detection. Lower detection limits are obtained using on-line SFE and HPLC analysis with fluorescence detection. PMID- 8480629 TI - A model for correcting Workplace Protection Factors for lung deposition and other effects. AB - The Workplace Protection Factor (WPF) is a measure of the protection provided by an industrial respirator against a challenge agent. It is traditionally defined as the ratio of the ambient contaminant concentration (Co) in a worker's breathing zone to the in-facepiece contaminant concentration (Ci) that occurs during inhalation, and is determined by simultaneous concentration measurements during the time the respirator is worn. There are several sources of particulate loss that result in the overestimation of the true WPF. A model is presented to "estimate" these losses so that an adjusted or "unbiased" WPF can be calculated. This model requires three measurements: Co, Ci, and the ambient aerodynamic mass frequency particle size distribution (PSD). Both Co and Ci are expressed in units of "mass per unit volume." There are four steps to the calculation of the unbiased WPF. First, the in-facepiece PSD is estimated using the ambient PSD and a particle leak penetration curve. Second, the fraction of the in-facepiece PSD that will deposit in the lung is estimated using the in-facepiece PSD and a "reference worker" total lung deposition curve. Third, the fraction of the in facepiece PSD that will deposit at the inlet of the sampling probe during both inhalation and exhalation is estimated using the in-facepiece PSD, the exhaled in facepiece PSD, and published inlet deposition data. Last, the adjusted in facepiece concentration is calculated using the estimates from steps two and three. The adjusted WPF, WPFa, is then calculated as the ratio of the measured ambient contaminant concentration and the adjusted in-facepiece concentration. PMID- 8480630 TI - Exposure of sprayers and plant handlers to mevinphos in Finnish greenhouses. AB - The exposure of sprayers and plant handlers to mevinphos, a toxic organophosphate insecticide, was evaluated in eight flower-growing greenhouses. The purpose was to assess an appropriate re-entry interval for mevinphos after its application in greenhouses. Inhalational and dermal exposure was measured during two days after application by measuring mevinphos in the greenhouse air and on the foliage. Workers' dermal exposure was measured with patch and handwash samples. The method of application considerably affected the levels of mevinphos in greenhouse air and on the foliage. The occupational exposure was measured with patch and handwash samples. The method of application considerably affected the levels of mevinphos in greenhouse air and on the foliage. The occupational exposure limit for mevinphos in Finland (100 micrograms/m3) was exceeded during the use of nonthermal foggers. Usually, however, the concentration of mevinphos in the breathing zone of the workers was below 10 micrograms/m3 9-12 hr after application. Mevinphos disappeared rapidly from greenhouse air and from the foliage after application, with a half-life of 9.2 hr. These data provide evidence that the main route of exposure to mevinphos is dermal, a conclusion supported by the excellent correlation between dermal exposure and the amount of mevinphos on the foliage. The calculated re-entry interval for mevinphos was approximately 4.5 hr. However, that interval is likely to be too short in practice because the risk of dermal exposure is considerable for more than 10 hr after the application of mevinphos. PMID- 8480631 TI - Electric and magnetic fields: what do we know? PMID- 8480632 TI - Exposure assessment for power frequency electric and magnetic fields. AB - Over the past decade considerable data have been collected on electric and magnetic fields in occupational environments. These data have taken the form of area measurements, source characterizations, and personal exposure measurements. Occupational EMF levels are highly variable in space and time. Exposures associated with these fields exhibit similar large variations during a day, between days, and between individuals within a group. The distribution of exposure measures is skewed over several decades with only a few values occurring at the maximum field levels. The skewness of exposure measures implies that large sample sizes may be required for assessments and that multiple statistical descriptors are preferred to describe individual and group exposures. Except for the relatively few occupational settings where high voltage sources are prevalent, electric fields encountered in the workplace are probably similar to residential exposures. Consequently, high electric field exposures are essentially limited to utility environments and occupations. Within the electric utility industry, it is definitely possible to identify occupations with high electric field exposures relative to those of office workers or other groups. The highly exposed utility occupations are linemen, substation operators, and utility electricians. The distribution of electric field exposures in the utility worker population is very skewed even within a given occupation. As with electric fields, magnetic fields in the workplace appear to be comparable with residential levels, unless a clearly defined high-current source is present. Since high current sources are more prevalent than high-voltage sources, environments with relatively high magnetic field exposures encompass a more diverse set of occupations than do those with high electric fields. Within the electric utility industry, it is possible to identify occupational environments with high magnetic field exposure relative to the office environment. Utility job categories with the highest exposures are generation facility workers, substation operators, utility linemen, and utility electricians. There are also higher exposures among traditional "electrical worker" job categories. Outside the electrical utility industry, potential sources of high occupational magnetic field exposures at ELF are induction furnaces, welding machines, electrical transportation systems, and electrical distribution vaults. However, the use of low power electrical equipment such as small motors in close proximity to workers and possibly for long periods of time could also lead to high exposure situations. Handheld survey instruments are available to perform area measurements of electric and magnetic fields at power frequencies but not aat all frequencies within the ELF range. Sophisticated personal computer-based instruments are available to characterize areas and sources across the entire frequency range.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8480633 TI - A review of in vitro studies: low-frequency electromagnetic fields. AB - In vitro studies of effects of low-frequency (LF) electromagnetic (EM) fields have revealed a variety of sensitive cell-physiologic end-points. Effects have been reported on (1) DNA, RNA, and protein synthesis; (2) cell proliferation; (3) cation fluxes and binding; (4) immune responses; and (5) membrane signal transduction (i.e., hormones, enzymes, and neuro-transmitters). Typically such effects occurred as a result of short-term exposure of cells to EM at frequencies of 100 Hz or less and at low field intensities. The dependency on frequency or modulation, as well as the apparent weak cellular interaction of these LF EM fields, lacks theoretic explanation. It has not been determined whether effects are induced by electric or magnetic fields. Confounding interpretation of the results are phenomena such as (1) transient or time-delayed responses; (2) modulation- and intensity-specific effects, referred to as modulation or intensity "windows;" and (3) general lack of dose- (or dose-rate) response data or EM field thresholds. Consequently, although it is well-established that LF EM fields affect biological systems in vitro, use of these data to assess human health effects is limited. This paper reviews selected published reports of LF EM fields on in vitro systems. Where possible, relevance of the findings to occupational exposures will be assessed, principally by considering the consistency of in vitro and in vivo EM exposure effects and comparison of EM field intensities that affect in vitro systems with occupational EM exposure intensities. Finally, suggestions will be made for the direction of future in vitro research of direct pertinence to potential occupational exposure problems. PMID- 8480634 TI - Biological effects of extremely low-frequency electromagnetic fields: in vivo studies. AB - This paper discusses the biological effects of exposure to extremely low frequency electromagnetic fields observed in animal studies. Three areas of investigation are reported: (1) studies on the nervous system, including behavior and neuroendocrine function; (2) experiments on cancer development in animals; and (3) measurements of currents and electric fields induced in animal models by exposure to external magnetic fields. An attempt is made to evaluate experimental results and interpret them with respect to potential health implications. PMID- 8480635 TI - Overview of epidemiologic research on electric and magnetic fields and cancer. AB - This overview of epidemiologic research addresses the potential role of 60 Hertz electric and magnetic fields (EMF) in the etiology of cancer. The key findings are summarized with notation of the methodological challenges with which investigators must content. Although exposure is ubiquitous, long-term average EMF is influenced primarily by the background levels in homes, use of selected electric appliances such as electric blankets, and workplace exposures to energized equipment. Studies of residential exposure have focused on childhood cancer, starting with the report of an excess of wire configurations associated with elevated magnetic fields near the homes of children who developed cancer compared to healthy children. Several subsequent studies have tended to confirm that association, although the evidence falls short of demonstrating a causal association between magnetic fields and cancer. Exposures from electric appliances have been less extensively pursued, with some suggestions of an association with childhood cancer. A more extensive literature has evaluated the association between workplace exposure to EMF, based on job titles of "electrical workers" and cancer. Across many different study designs and settings, certain groups of electrical workers show elevated occurrence of leukemia and brain cancer. The consistency of findings is notable, but the key question is whether the association with job title is due to EMF or some other agent in the workplace. Future research would benefit from specification of testable challenges to a causal association between EMF exposure in the home or workplace and cancer, along with continued efforts to improve our understanding and measurement of EMF exposure. PMID- 8480636 TI - Electric and magnetic field management. AB - The emergence of new electrical technologies has produced an extremely complex electric and magnetic field environment in which we must live and work. Although there presently exist no universally accepted human exposure guidelines, current biological research may someday produce such limits. It is in anticipation of these exposure limits that electric and magnetic field management techniques are being investigated. At low frequencies, two categories of field management exist: cancellation and shielding. The particular class of control used will depend on several functions of the field and its source, and will be determined finally on a case-by-case basis. In general, it is found that magnetic fields are much more complicated to manage than electric fields. The discussion of this paper serves as a primer in the area of low frequency electric and magnetic fields and the control thereof. PMID- 8480637 TI - Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia. AB - A combined use of noninvasive techniques and electrophysiologic study in the prediction of arrhythmic events was prospectively evaluated in 303 surviving patients of acute myocardial infarction (AMI). The most powerful combination of noninvasive prognostic variables in identifying patients suitable for invasive strategies was also assessed. Patients who had > or = 2 variables among left ventricular ejection fraction < 0.4, ventricular late potentials and repetitive ventricular premature complexes (VPCs) were considered eligible for programmed ventricular stimulation. After 15 +/- 7 months of follow-up, 19 patients (6%) had an arrhythmic event. Left ventricular dyskinesia (p < 0.00001) and ejection fraction < 0.4 (p < 0.000001), late potentials (p < 0.001), filtered QRS duration > or = 106 ms (p < 0.00001), VPCs/hour > 6 (p < 0.05), paired VPCs (p < 0.01), > or = 2 runs of unsustained ventricular tachycardia (VT) per monitoring (p < 0.001), heart rate variability index < or = 29 (p < 0.00001) and mean RR interval < or = 750 ms (p < 0.01) were found to be significant univariate predictors of events. At multivariate analysis, only low left ventricular ejection fraction, prolonged filtered QRS duration, reduced heart rate variability index and detection of > or = 2 runs of unsustained VT per monitoring had an independent relation to late arrhythmic events. Of 67 eligible patients, 47 (70%) consented to undergo programmed stimulation. A positive electrophysiologic study was found to be the strongest independent predictor of events among patients preselected by noninvasive techniques. With a good sensitivity (81%), a combined use of noninvasive tests and electrophysiologic study selected a group of post-AMI patients at sufficiently high risk (event rate 65%) to be considered candidates for interventional therapy. The combination of > or = 2 variables among left ventricular ejection fraction < 0.4, filtered QRS duration > or = 106 ms and > or = 2 runs of unsustained VT was superior to the other ones in identifying high risk subjects (positive and negative predictive values for arrhythmic events of 44 and 99%, respectively). On the basis of the data, this scheme appears to be the most appropriate for selecting patients suitable for electrophysiologic testing and invasive strategies after AMI. PMID- 8480638 TI - Prognostic significance of early ischemia after acute myocardial infarction in low-risk patients. IRES (Ischemia Residua) Study Group. AB - Early postinfarction angina is generally believed to imply an unfavorable prognosis. However, most of the published information devices from data collected in the prethrombolytic era, with widely differing populations and definitions of early angina, and very little data pertinent to low-risk patients are available. This collaborative study prospectively assessed the incidence of early recurrent ischemia after thrombolysis, as well as its prognostic significance, in 453 consecutive patients aged < or = 70 years with an uncomplicated course in the first 24 hours of a first myocardial infarction participating in the second Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI 2) trial. Early recurrent ischemia (spontaneous, transient ST depression or elevation of > 1 mm and/or T-wave inversion), assessed in the coronary care unit with continuous clinical and electrocardiographic monitoring, was documented in 35 of 453 patients (8%) and was unrelated to sex, age, electrocardiographic location, Q-wave or non-Q-wave infarction, thrombolytic agent and time to its administration. In-hospital cardiac events (7 deaths, 19 nonfatal reinfarctions and 8 urgent revascularizations) occurred in 15 of 35 patients (43%) with versus 19 of 418 without (4.5%) recurrent ischemia (p < 0.001). At the 6-month follow-up of 352 medically treated patients who did not have in-hospital events, the incidence of death, reinfarction and recurrent angina was comparable between patients with (2 of 18, 11%) and without (62 of 334, 19%) early ischemia (p = NS). With use of stepwise multivariate analysis, early ischemia was the only significant predictor of in-hospital cardiac events (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480639 TI - Five- to ten-year outcome after multivessel percutaneous transluminal coronary angioplasty. AB - The early and late outcome of patients who underwent multivessel percutaneous transluminal coronary angioplasty (PTCA) in a 1-stage procedure are described, and the predictors for clinical event and new revascularization procedure are identified. Of 1,937 patients treated by PTCA between 1981 and 1986, 203 (10.4%) had multivessel PTCA in a 1-step procedure. A follow-up extending to 71 +/- 23 months was obtained in 195 patients (96%). Primary success was achieved in 91% of 494 attempted sites, and complete revascularization in 65% of 203 patients. There were no in-hospital deaths. Acute complications occurred in 13 patients (6.4%), including non-Q-wave (n = 8) and Q-wave (n = 5) infarction, and urgent coronary artery bypass surgery (n = 3). Before PTCA, 126 patients (62%) were in class III or IV of the Canadian Cardiovascular Society classification; at follow-up, 84% were angina-free or in class I. Death occurred in 14 patients and nonfatal myocardial infarction in 18. Angiographic restenosis was diagnosed in 37.2% of dilated lesions in 96 patients (60% of 159 restudied). A repeat revascularization procedure for restenosis or progression of disease, or both, was needed in 92 symptomatic patients (47%). The survival rate at 7 years without the need for surgery or PTCA was 53%, and cardiac survival without myocardial infarction was 85.5%. The only independent predictor of cardiac death was ejection fraction (p < 0.001). The rate of restenosis per patient was primarily determined by the number of segments dilated, whereas progression of disease was related to the number of nonsignificant coronary artery stenoses (< 50%) at baseline (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480640 TI - Recent changes in the management and outcome of acute closure after percutaneous transluminal coronary angioplasty. AB - The major cause of morbidity and mortality associated with percutaneous transluminal coronary angioplasty (PTCA) is acute closure. This study compared the clinical outcome of 2 groups of patients who experienced acute closure during PTCA. One group was treated during a period when intracoronary stents, laser balloons and perfusion balloons were available for treatment of acute closure (group II). These results were compared with the clinical outcome a group of similar patients who were treated for acute closure during a period that immediately preceded the availability of these devices (group I). One hundred sixty-six patients had acute closure in group I, whereas 156 patients experienced acute closure in group II. Baseline clinical characteristics were similar for both groups. There was no difference in ejection fraction, number of vessels diseased, degree of stenosis or number of vessels attempted between the 2 groups. Patients in group II had more balloon inflations and longer balloon inflation times when compared with patients in group I. Of the 156 patients in group II, 47% were treated with either an intracoronary stent, laser balloon or perfusion balloon. Group II patients had fewer Q-wave myocardial infarctions (9.1 vs 20.3%, p = 0.005). In addition, peak creatine phosphokinase levels (826 +/- 1,515 vs 517 +/- 1,050, p < 0.01) and mean residual stenosis (40.7 +/- 33.2 vs 58.0 +/- 34.4%, p < 0.0001) were also lower in group II patients. There was also less coronary artery bypass grafting during the same admission (38.6 vs 29.5%, p = 0.02) in group II patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480641 TI - Effects of aspirin DL-lysine on thrombin generation in unstable angina pectoris. AB - To evaluate the effects of aspirin on thrombin generation in patients with unstable angina, plasma levels of thrombin-antithrombin III complex (TAT) as a new marker of thrombin generation and of 11-dehydro-thromboxane B2 (11-dehydro TXB2) as an indicator of platelet activation were measured in 18 patients with unstable angina, including 8 patients with prolonged rest angina (> 15 minutes). Aspirin DL-lysine (900 mg) was administered intravenously to 9 of the 18 patients (aspirin group); the other 9 were not given aspirin during the first 24 hours of hospitalization (non-aspirin group). Clinical characteristics, angiographic features and medications other than aspirin were similar between the 2 groups. Levels of plasma TAT and 11-dehydro-TXB2 were significantly higher (p < 0.05) in patients with prolonged rest angina than in those without the condition (n = 10). In 5 patients with prolonged rest angina who received aspirin, plasma TAT levels (ng/ml) were significantly decreased (4.52 +/- 1.18 at baseline, 2.50 +/- 0.65 at 1 hour and 2.16 +/- 0.42 at 24 hours after aspirin administration, p < 0.01) with a significant decrease in plasma 11-dehydro-TXB2 levels. However, the reduction in TAT after aspirin administration was slight in patients without prolonged rest angina (n = 4). In contrast, levels of plasma TAT and 11-dehydro-TXB2 in the non aspirin group remained unchanged during the study period. These results suggest that aspirin rapidly reduces thrombin generation through inhibition of platelet activity in patients with unstable angina with prolonged rest angina. PMID- 8480642 TI - Clinical significance of morphologic classification of coronary arterial segmental stenosis due to Kawasaki disease. AB - Coronary arteriograms obtained in 1,392 patients from a cohort of 4,562 with Kawasaki disease showed 395 to have coronary arterial lesions. The specific lesions, known as segmental stenoses, were observed in 62 patients, involving 68 coronary arterial branches. The lesions involved the right coronary artery in 56 cases (14.2% of the group with arterial lesions) and the left coronary artery in the other 12 (3% of the overall group with arterial lesions). Three morphologic variations were observed. Braid-like lesions accounted for 15 lesions, involving the right coronary artery and occurring < 2 years after the onset of Kawasaki disease. Bridging vessels were observed in 40 of 68 arterial lesions, 30 of which involved the right coronary artery. Of these bridging vessels, 86% were present within 4 years of onset of the disease. Pericoronary communications were observed in the remaining 13 of 68 lesions, 11 involving the right coronary artery and appearing at variable intervals, but usually significantly later than the other lesions. Myocardial ischemia was found at the first study in 60% of braid-like lesions, but in only 29% of the lesions at follow-up studies. Of bridging vessels or pericoronary communications, 95 and 77%, respectively, were found to have produced ischemia in the initial study, which persisted in 78 and 77%, respectively. There are 3 different mechanisms involved in the formation of segmental stenosis, with different prognoses for the clinical course of myocardial ischemia. PMID- 8480643 TI - Radiofrequency ablation in multiple accessory pathways and the physiologic implications. AB - The presence of multiple accessory pathways was noted in 24 of 210 consecutive patients (12 males and 12 females aged 15 to 77 years [mean +/- SD 43 +/- 16]) with the Wolff-Parkinson-White syndrome who underwent electrophysiologic study and radiofrequency ablation. Six had 3 and 18 had 2 accessory pathways. There were 25 manifest and 29 concealed accessory pathways. The location of the accessory pathways was in the left free wall in 22, the right free wall in 17, the left posterior portion of the ventricular septum in 8, the right posterior portion of the ventricular septum in 6, and the midseptum in 1. The success rate of accessory pathway ablation and the fluoroscopic time in these 24 patients with multiple accessory pathways were 89% and 78 +/- 66 minutes, respectively, whereas they were 98% (p < 0.01) and 36 +/- 37 minutes (p = 0.01) in the 186 patients with a single accessory pathway. The mean applications, the power level of the radiofrequency current and the application duration in these 24 patients were 21 +/- 22, 30 +/- 3 W, and 27 +/- 10 seconds, respectively. In the 186 patients with a single accessory pathway, they were 9 +/- 12 applications (p = 0.02), 30 +/- 4 W (p = NS) and 26 +/- 9 seconds (p = NS), respectively. Seventeen of the 24 patients had a follow-up electrophysiologic study 89 +/- 40 days after ablation, and 2 (12%) had resumption of a right and left accessory pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480644 TI - Factors determining late success after mitral balloon valvulotomy. AB - Mitral balloon valvulotomy (MBV) has proved to be an effective method in the treatment of patients with mitral stenosis. Although several factors determining an optimal immediate result have been described, there is little information regarding long-term follow-up, as well as factors influencing late success after MBV. This study analyzes 350 patients (mean age 46 +/- 12 years) treated by MBV who were clinically followed up between 6 months and 6 years. At least 1 echo Doppler follow-up study was obtained in 298 patients 28 +/- 14 months after MBV; hemodynamic reevaluations were performed in 66 patients after 23 +/- months. Late success was considered if the patient was in functional class I to II and free of major events (death, restenosis and valve surgery). Restenosis was defined as a 50% loss of initial gain with regard to valve area by echocardiography, which was confirmed hemodynamically. After a mean follow-up of 38 +/- 15 months, 296 patients (84%) remained in functional class I to II, without surgery or the need for an increase in medical treatment. The 5-year Kaplan-Meier survival rate was 94 +/- 1%, whereas restenosis, valve surgery and major event-free probability were 90 +/- 3%, 91 +/- 2% and 85 +/- 2%, respectively. Multivariate study (Cox regression model) identified the presence of sinus rhythm (p < 0.001) and the absence of calcium at fluoroscopy (p < 0.003) as the only independent factors of late success.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480645 TI - Clinicopathologic features of active infective endocarditis isolated to the native mitral valve. AB - Although a number of clinicopathologic studies in patients with active infective endocarditis (IE) have been reported, none have focused on patients studied at necropsy with active IE isolated to the mitral valve. We studied at necropsy 63 patients (aged 12 to 88 years [mean 50], 44 males [70%]) with active IE limited to the native mitral valve: 21 (33%) had preexisting mitral valve disease (rheumatic in 8, prolapse in 3, hypertrophic cardiomyopathy in 1, and mitral annular calcium in 9), and the other 42 patients (67%) had previously normal mitral valves. Of the latter 42 patients, 22 (52%) had recognized predisposing factors to IE: opiate addiction in 14, habitual alcoholism in 6 and/or chronic hemodialysis in 4. Staphylococcus aureus or epidermidis was the responsible organism in 32 patients (51%), and the active IE was associated with an infection elsewhere in the body in 31 patients (50%). The active IE caused rupture of mitral chordae tendineae in 11 patients (18%), perforation of the anterior mitral leaflet in 7 patients (11%), and mitral ring abscess in 10 patients (16%). Grossly visible systemic emboli were found in 44 patients (70%) and 33 (52%) had infarcts in 1 or more body organs. Thus, active IE isolated to the mitral valve in necropsied patients appears to be more common in males than females (2 to 1); the infection more commonly than not involves a preexisting anatomically normal valve rather than a preexisting abnormal one (2 to 1); the vegetations often do not cause or worsen valvular dysfunction; a predisposing factor is commonly present (2 of 3 patients), and the IE commonly is part of a generalized or systemic infection (1 of 2 patients). PMID- 8480646 TI - Retrobronchial vertical vein in totally anomalous pulmonary venous connection to the innominate vein and its specific occurrence in right isomerism. AB - Recently, a case of right isomerism with totally anomalous pulmonary venous connection (TAPVC) to the innominate vein through a vertical vein that ascended in the mediastinum posterior to the left-sided main bronchus was encountered. This retrobronchial vertical vein that has not been described previously in patients with TAPVC to the innominate vein prompted the performance of a retrospective analysis of 44 cases with TAPVC to the innominate vein in which angiography had been performed. The 44 cases consisted of 36 patients with situs solitus, 7 with right isomerism, and 1 with left isomerism. The spatial relation of the vertical vein to the adjacent pulmonary artery and main bronchus could be defined in 41 cases. The vertical vein was retrobronchial in 4 of 5 cases with right isomerism in which the location of the vertical vein could be defined with certainty. No case with situs solitus or left isomerism was associated with a retrobronchial vertical vein. In all 4 patients with a retrobronchial vertical vein, angiographic evidence of obstruction of pulmonary venous drainage was present, and was due to an extrinsic bronchial compression in 2 and to an intrinsic narrowing of the vertical vein in 2. PMID- 8480647 TI - Relation of elevated plasma endothelin in congenital heart disease to increased pulmonary blood flow. AB - Endothelin-1 (ET), a potent vasoconstrictor peptide, has been found to be elevated in children with pulmonary hypertension associated with congenital heart defects. To evaluate the effect of pulmonary blood flow on ET concentrations, 5 ml blood samples were obtained peripherally at cardiac catheterization from 35 patients, ages 0.13 to 17 years (median 2). Plasma was extracted and ET measured by radioimmunoassay. Patients were classified into 2 groups based on the presence (group A) or absence (group B) of increased pulmonary blood flow defined as a Qp/Qs > or = 1.5. When the 13 patients (37%) in group A were compared with the 22 patients (63%) in group B there were no significant differences in age, cardiac index, or pulmonary and systemic resistances. ET concentrations were significantly higher in group A patients (median 3.25, range 0 to 16.5 vs median 0, range 0 to 6.35 pg/ml; p < or = 0.05). Pulmonary blood flow and pulmonary artery pressure were also higher in group A patients (p < or = 0.01). When patients within group A were subdivided into those with and without pulmonary hypertension, no difference was present in their ET concentrations (mean/SD: 4.4/4.3 vs 4.0/6.4 pg/ml, p = NS). Thus, ET is elevated in patients with congenital heart disease associated with left-to-right shunts and it appears that this increase is related to increased pulmonary blood flow independent of pulmonary artery pressure. PMID- 8480648 TI - Detection of atherosclerotic lesions in the aorta by transesophageal echocardiography. AB - Transesophageal echocardiographic studies were prospectively performed in 152 consecutive patients older than age 40 years referred to the echocardiography laboratory to assess the prevalence of atherosclerosis in the thoracic aorta and relate this to a history of systemic embolization. Forty-four patients (29%) had at least 1 atherosclerotic lesion in the thoracic aorta. This was associated with a higher prevalence of coronary artery disease (78% of all patients with coronary artery disease), carotid artery disease (88% of all patients with carotid artery disease) and peripheral vascular disease (all symptomatic patients). Forty-two of all patients (28%) had systemic emboli, 20 (48%) of whom had at least 1 atheromatous lesion in the thoracic aorta. Conversely, only 24 of 110 patients (22%) without previous systemic emboli had atheromatous lesions (p < 0.001). It is concluded that atherosclerotic lesions in the thoracic aorta can readily be identified with transesophageal echocardiography. The detection of atherosclerotic plaques of the aorta represents a marker of diffuse atherosclerotic disease, often associated with carotid, coronary and peripheral vascular disease and with the occurrence of systemic emboli. Transesophageal echocardiography may be used serially to investigate whether dietary or pharmacologic maneuvers, or both, can shrink established atherosclerotic plaques in the thoracic aorta. PMID- 8480649 TI - Comparison of activated partial thromboplastin time to activated clotting time for adequacy of heparin anticoagulation just before percutaneous transluminal coronary angioplasty. PMID- 8480650 TI - Comparison of major complication rates with new atherectomy devices for percutaneous coronary intervention in women versus men. PMID- 8480651 TI - Direct holmium laser-assisted balloon angioplasty in acute myocardial infarction. PMID- 8480652 TI - Six-month quantitative angiographic follow-up of < 50% diameter stenoses dilated during multilesion percutaneous transluminal coronary angioplasty. PMID- 8480653 TI - Frequency of unfavorable cardiac events documented by routine telemetry monitoring after uncomplicated percutaneous transluminal coronary angioplasty. PMID- 8480654 TI - Interleukin-6 (IL-6) as a mediator of stunned myocardium. PMID- 8480655 TI - Prevalence of reciprocating tachycardia in patients aged < 50 years with apparent lone atrial fibrillation. PMID- 8480656 TI - Rapid bedside temporary pacing by the right supraclavicular subclavian vein approach. PMID- 8480657 TI - Long-term survival in the Munich Mild Heart Failure Trial (MHFT). PMID- 8480658 TI - Variability of mitral valve area by Gorlin formula after replacement by a caged ball prosthesis. PMID- 8480659 TI - Discrepancies between Doppler and catheter gradients across bileaflet aortic valve prostheses. PMID- 8480660 TI - Percutaneous balloon mitral valvotomy in patients with history of embolism. PMID- 8480661 TI - Frequency of acquired coronary-cameral fistula after ventricular septal myectomy in hypertrophic cardiomyopathy. PMID- 8480662 TI - Determinants for outcome of balloon valvuloplasty for severe pulmonary stenosis in neonates and infants up to six months of age. PMID- 8480663 TI - The 12-lead electrocardiogram of "healthy" ambulatory subjects with positive Lyme immunoserology. PMID- 8480664 TI - Relation between mitral annular calcium and complex intraaortic debris. PMID- 8480665 TI - Electrocardiographic changes during long-term follow-up of pediatric heart transplant recipients. PMID- 8480666 TI - Ego-state therapy: an overview. AB - Ego-state therapy is a psychodynamic approach in which techniques of group and family therapy are employed to resolve conflicts between the various "ego states" that constitute a "family of self" within a single individual. Although covert ego states do not normally become overt except in true multiple personality, they are hypnotically activated and made accessible for contact and communication with the therapist. Any of the behavioral, cognitive, analytic, or humanistic techniques may then be employed in a kind of internal diplomacy. Some 20 years experience with this approach has demonstrated that complex psychodynamic problems can often be resolved in a relatively short time compared to more traditional analytic therapies. PMID- 8480667 TI - The use of ego-state therapy in the treatment of posttraumatic stress disorder. AB - Ego-state therapy has been cited in the literature as a promising tool for the treatment of patients who suffer from the effects of past trauma experiences. In this paper, I review various methods to activate ego states and to uncover traumatic experiences and their related internal conflicts in sexually abused patients with posttraumatic symptoms. I also discuss ego-state-therapy techniques that promote the integration and resolution of trauma. Three clinical case examples illustrate the use of ego-state therapy with posttraumatic patients. I suggest ways in which ego-state-therapy methods can be useful with some of the symptomatology specific to this population. The effectiveness of ego-state therapy is also explored in dealing with certain features of posttraumatic conditions that can complicate treatment, including dissociation and fragmentation, cognitive and perceptual distortion, and rigidification of personality and behavior. PMID- 8480668 TI - From strength to strength: "inner strength" with immature ego states. AB - The ego-strengthening literature concentrates on the use of hypnotic techniques with the entire or total personality. Ego-state therapy conceptualizes the ego as a system of subpersonalities or ego states that have shifting energies. At any particular time the ego state with the most energy is dominant or executive. Any technique that can be used with an individual patient can also be used with an identified ego state. The "inner-strength" hypnotic technique has been used for ego strengthening and mobilization of inner resources. In this paper the "inner strength" technique is used with ego states that have been identified as responsible for specific symptoms. We will discuss indications for the appropriate use of this technique in ego-state therapy and the mechanisms of its role in the resolution of symptoms in the cases presented. PMID- 8480669 TI - Ego-state therapy for self-injurious behavior. AB - The authors describe the use of ego-state therapy for the treatment of self injurious behavior (SIB). We propose that for some patients, SIB results from conflict among dissociated ego states. We review the historical and theoretical basis for this position and delineate a specific treatment technique. Our strategy consists of identifying an ego state in which SIB occurs, activating the patient's ego strengths using inner-adviser techniques and facilitating the integration of these resources within the ego state responsible for the behavior. We have used this strategy with favorable results for patients with dissociative symptoms, primarily those suffering from borderline personality disorder, posttraumatic stress disorder, or dissociative disorders. PMID- 8480670 TI - Therapeutic writing as a form of ego-state therapy. AB - In this paper I describe a special form of ego-state therapy that integrates writing letters to one's self as an internal therapeutic communication among various ego states previously not fully aware of each other or engaged in destructive power struggles. Expressing one's thoughts, feelings, and urges in writing transforms primary process activities of the self into secondary processes that are more mature and adaptive to healthy functioning in day-to-day living. This method also reinforces the idea of patient empowerment in the form of self-healing and utilizing internal resources in the process of recovery. PMID- 8480671 TI - Accessing the relevant areas of maladaptive personality functioning. AB - Personality functions in different dimensions: perceptual, cognitive, and affective (emotional). It can be manifested in different areas--overt (conscious), covert (unconscious), or in some relative degree of each. Personality segments can operate independently of one another, as in multiple personalities or with varying degrees of mutual dependence and intercommunication, as in normal "ego states." Therapeutic interventions will be more efficient if focused within the problem dimension, area, or segment. The essence of Alexander and French's "corrective emotional experience" was a restructuring of the patient through release and interpretation within the "emotional" sphere. When their concept is extended to other dimensions of personality functions, such as behavioral, perceptual, and cognitive, it allows interventions to be more specifically focused in the regions that are most relevant. In this paper we present specific techniques using this extended concept. Rapid and significant change followed in the patient so treated. PMID- 8480672 TI - Research directions in nutrition: view from the NICHD. PMID- 8480673 TI - Accuracy of measurements of body composition by dual-energy x-ray absorptiometry in vivo. AB - The accuracy of body-composition measurements in vivo by dual-energy x-ray absorptiometry (DEXA) was assessed in seven pigs (weight: 35-95 kg) by measurement by DEXA in vivo and chemical analysis after postmortem homogenization. The regression lines between these measurements were not significantly different from the line of identity (P > 0.05), the r values were > 0.97, and the corresponding SEEs were 2.9%, 1.9 kg, and 2.7 kg for percent fat, fat tissue mass, and lean body mass, respectively. Changes in fat and lean tissue mass (simulated by placing 8.8 kg porcine lard on the trunk of six women) were accurately measured by DEXA. The measured total-body bone mineral (TBBM) was significantly affected by the lard (P < 0.05). In conclusion, DEXA is an accurate method for measurement of soft-tissue body composition. TBBM measurements in longitudinal studies may, however, be difficult to interpret if considerable change in soft-tissue composition has occurred. PMID- 8480674 TI - Advantage of knee height over height as an index of stature in expression of body composition in adults. AB - It is not clear how body composition should best be compared between subjects, but it is accepted that simply comparing total mass or percentage fat-free mass (FFM) or fat mass (FM) is not adequate. Indexing body composition to stature seems more appropriate, but the decline in height with age or osteoporosis could confound comparisons of body composition across age or disease groups. Using bioimpedance data from 600 adults in the Framingham Offspring Study, we examined the ability of height and knee height indexes to correctly describe the loss of FFM seen with increasing age between 28 and 75 y. Indexing body composition to height obscured the loss of FFM with age (r = -0.065, P < 0.26 for men; r = 0.050, P < 0.394 for women), whereas indexing body composition to knee height preserved the correct information (r = -0.154, P < 0.007 for men; r = -0.161, P < 0.006 for women). These data suggest that knee height is a reliable surrogate for stature and should be used to adjust body composition measurements when bioimpedance is used to estimate body composition. PMID- 8480675 TI - Resting energy expenditure in human immunodeficiency virus-infected patients: comparison between patients with and without secondary infections. AB - Resting energy expenditure (REE) was measured in 165 malnourished patients with human immunodeficiency virus infection and compared with that of 31 control subjects. Of these patients, 129 had no symptoms of secondary infections (NI), whereas 36 had evolving secondary infection (I) despite a body temperature < 38 degrees C. Mean REE was 11% higher in the NI group than in the control group (P < 0.05); it was 34% higher in the I group than in the control group (P < 0.001) and 21% higher than in the NI group (P < 0.01). In all cases the best predictive variable for REE was the fat-free mass (FFM) (r = 0.77, P < 0.001 in NI; r = 0.70, P < 0.001 in I; r = 0.78 in the control group. The REE-FFM ratio was 152.5 +/- 1.2 and 207 +/- 5.4 kJ.kg-1.d-1 in the NI and I groups, respectively. A high energy expenditure may be a harbinger of secondary infection in acquired immunodeficiency syndrome and may participate in accelerated weight loss. PMID- 8480676 TI - Seasonality of energy expenditure during pregnancy and lactation for rural Nepali women. AB - Total energy expenditure (TEE) was estimated for 19 nonpregnant, nonlactating (NPNL) and 24 pregnant (P) or lactating (L) women from 3601 h of minute-by-minute observation and 168 measurements of the energy cost of activities. NPNL women significantly increased subsistence activity and TEE from 9.9 MJ [1.89 x basal metabolic rate (BMR)] in the winter to 10.5 MJ (2.01 x BMR) in the monsoon season. There were differences between NPNL,P, and L women in the winter, but not in the spring or monsoon season when all individuals sustained very heavy physical activity. High TEE values resulted from spending very long hours in tasks that, although appearing physically demanding to the casual observer, were characterized by light or moderate energy cost. The study highlights the importance of seasonal constraints on women's work, which prevent P and L women from significantly curtailing physical activity during the monsoon season, and which effectively limit the scope of behavioral mechanisms for saving energy and reducing TEE. PMID- 8480677 TI - Adipose tissue fatty acids as biomarkers of dietary exposure in Danish men and women. AB - Adipose tissue fatty acids, it has been proposed, reflect dietary intake. Using data from a validation study preceding a prospective study on diet, cancer, and health in Denmark, we were able to compare fatty acid profiles in adipose tissue biopsies from 86 individuals (23 men and 63 women) aged 40-64 y and dietary intake of fatty acids (as percentage of total fat) assessed by two 7-d weighed diet records or by a semi-quantitative food frequency questionnaire. Correlation coefficients (Pearson r) between fatty acid concentrations in adipose tissue biopsies (as percentage of total peak area) and dietary intake of fatty acid (percentage of total fat), determined from the diet records for men and women, respectively, were as follows: polyunsaturated fatty acids r = 0.74 and r = 0.46; n - 3 fatty acids of marine origin: eicosapentaenoic acid r = 0.15 and r = 0.61, and docosahexaenoic acid r = 0.47 and r = 0.57. Correlation coefficients obtained by using the food frequency questionnaire were slightly lower for most fatty acids. PMID- 8480678 TI - Individual effects of dietary saturated fatty acids and fish oil on plasma lipids and lipoproteins in normal men. AB - Fish ingestion is associated with lower mortality from coronary heart disease (CHD). However, in some Western populations whose diets are rich in saturated fatty acids (SFAs), CHD mortality is consistently high despite high fish consumption. To study this paradox, we fed six healthy men diets with two amounts of SFA (5% and 19% of energy) that also differed in total fat (25% and 39% of energy). Each fat amount was given with and without n-3 fatty acids (FAs) (2% of energy) for 3 wk. On both the low and high SFA diets the presence of n-3 FAs significantly lowered plasma total cholesterol, very-low-density-lipoprotein cholesterol, (high-density-lipoprotein cholesterol (HDL-C), total triglyceride, and very-low-density-lipoprotein triglyceride. Compared with the high SFA diet, the low SFA diet decreased total cholesterol, low-density-lipoprotein cholesterol, and HDL-C. No interaction of SFA and n-3 FA was found. These results indicate that dietary SFAs and n-3 FAs have independent mechanisms of actions on the plasma lipids and lipoproteins. Optimal plasma lipids were produced by the diet low in SFA and high in n-3 FA. PMID- 8480679 TI - Marked increase in plasma high-density-lipoprotein cholesterol after prolonged fasting during Ramadan. AB - We evaluated the effect of the Ramadan fasting on plasma lipids and lipoproteins in normal individuals. Twenty-four healthy subjects were studied before the end of the Ramadan month (Ram) and for 1 mo thereafter. Plasma total cholesterol (TC), triglycerides, low-density-lipoprotein cholesterol (LDL-C), and very-low density-lipoprotein cholesterol (VLDL-C) did not change. High-density-lipoprotein cholesterol (HDL-C) was 30% higher (P < 0.005) at the end of Ram; apolipoprotein A-I also increased (P < 0.0001). Both the ratios of TC to HDL-C and LDL-C to HDL C (P < 0.001) decreased at Ram. There was a striking nonpharmacologic improvement in plasma HDL-C and ratios of TC to HDL-C and LDL-C to HDL-C, which were most probably induced by eating one large evening meal a day. Further studies to determine the mechanism of this observation are underway. PMID- 8480680 TI - Rapid incorporation of fish or olive oil fatty acids into rat hepatic sinusoidal cell phospholipids after continuous enteral feeding during endotoxemia. AB - Therapeutic modalities that downregulate macrophage and endothelial production of eicosanoid mediators by displacing membrane arachidonic acid (20:4 omega 6) may benefit patients at increased risk of septic complications. The objective of this study in rats was to assess the incorporation of fish or olive oil fatty acids into hepatic Kupffer and endothelial (K&E) cell phospholipids after 4 d of continuous enteral feeding during endotoxemia. Either endotoxin (ETX) (0.5-1 mg 1.day-1) or vehicle was infused intravenously during the last 72 h. Dietary fish and olive oil fatty acids were rapidly incorporated into both K&E and plasma phospholipids irrespective of ETX cotreatment. Rats infused with the fish oil enriched diet had a significantly lower relative percent of both K&E linoleic acid (18:2 omega 6) and 20:4 omega 6, whereas rats infused with the olive oil enriched diet only had a lower relative percent of 18:2 omega 6 compared with control rats receiving corn oil. Provision of specific dietary lipids by continuous enteral infusion may prove efficacious for the rapid modulation of hepatic sinusoidal cell membrane fatty acids under either normal or endotoxemic conditions. PMID- 8480681 TI - Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. AB - Ten control (healthy) subjects and 15 non-insulin-dependent diabetics underwent an oral glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). In control subjects (placebo-treated vs vitamin E-supplemented subjects, respectively) vitamin E reduced the area under the curve for glucose (344 +/- 21 vs 287 +/- 13 mmol.L-1 x min-1; P < 0.05) and increased total body glucose disposal (39.0 +/- 0.3 vs 47.6 +/- 0.4 mumol.kg lean body mass-1 x min-1; P < 0.05) and non oxidative glucose metabolism (23.4 +/- 0.2 vs 30.8 +/- 0.3 mumol.kg lean body mass-1 x min-1; P < 0.05). In diabetics (placebo-treated vs vitamin E supplemented subjects, respectively) vitamin E supplementation reduced glucose area under the curve (614 +/- 129 vs 544 +/- 98 mmol.L-1 x min-1; P < 0.03) and increased glucose disappearance (19.4 +/- 0.4 vs 26.4 +/- 0.7 mumol.kg lean body mass-1.min-1; P < 0.03), total glucose disposal (19.0 +/- 0.7 vs 28.1 +/- 0.4 mumol.kg lean body mass-1 x min-1; P < 0.02), and nonoxidative glucose metabolism (8.5 +/- 0.3 vs 13.9 +/- 0.3 mumol.kg lean body mass-1 x min-1; P < 0.02). Therefore we conclude that administration of pharmacologic doses of vitamin E is a useful tool to reduce oxidative stress and improve insulin action. PMID- 8480682 TI - Positive association between serum zinc and apolipoprotein A-II concentrations in middle-aged males who regularly consume alcohol. AB - The relationship of serum zinc with serum concentrations of lipids and apolipoproteins was investigated in 464 male clerical workers aged 35-59 y. Subjects were divided into three groups, by drinking habits. Serum triglycerides, apolipoprotein (apo) A-I, and apo A-II in occasional (2-5 times/wk) and regular (> or = 6 times/wk) drinkers were higher than in non- or seldom (< 1 time/wk) drinkers, whereas serum zinc, total cholesterol (TC), and apo B were not different among groups. Significantly higher high-density-lipoprotein cholesterol (HDL-C) and HDL-C% (HDL-C/TC%) were observed in regular drinkers. Correlation analysis revealed that the serum zinc concentration was positively correlated with apo A-II only in the regular drinkers, and the relationship was significant even after body mass index, smoking habits, and frequency of physical exercise were adjusted for. The results suggest that the individual response of the apo A II concentration to alcohol is associated with zinc nutritional status in regularly drinking middle-aged men. PMID- 8480683 TI - Toenail selenium as an indicator of selenium intake among middle-aged men in an area with low soil selenium. AB - Toenail selenium concentration has been proposed as a long-term (6-12 mo) indicator of human selenium status. This study investigated the association between toenail selenium concentration and selenium intake and other dietary factors among 166 urban men aged 55-69 y. The dietary information was collected by food records covering a 6-mo period. Toenail clippings were collected by mail 9-10 mo after food recording. The mean selenium intake from food was 42.5 micrograms/d and the dietary intake was equal to that of users and nonusers of selenium supplements. The mean toenail selenium concentration was 0.47 mg/kg. The mean selenium intake from supplements was 29.7 micrograms/d among supplement users. In the analysis of covariance the best predictors of toenail selenium concentration were selenium intake from supplements and food, and among supplement users dietary beta-carotene also. PMID- 8480684 TI - Low red blood cell glutathione reductase and pyridoxine phosphate oxidase activities not related to dietary riboflavin: selection by malaria? AB - This study was designed to confirm that low dietary riboflavin does not contribute to the flavin-deficient red blood cells commonly found in subjects in Ferrara Province, northern Italy. In this area it is primarily an inherited characteristic believed to have been selected for by malaria, which was endemic from the 12th century. In parallel with assessment of daily riboflavin intake (DRI), flavin adenine dinucleotide-dependent glutathione reductase (EGR) and flavin mononucleotide-dependent pyridoxine phosphate oxidase (PPO) were measured in beta-thalassemic heterozygotes, their normal relatives, and normal spouses (representative of the normal population). In all of these groups there is a high incidence of deficiency of these flavin enzymes. We found that the majority had an adequate riboflavin intake and there was no significant correlation of EGR and PPO activities with DRI. Thus, interpretation of low EGR activity is discussed with reference to studies of EGR done to detect nutritional riboflavin deficiency in countries where there is malnutrition and endemic malaria. PMID- 8480685 TI - The effect of zinc supplementation on parasitic reinfestation of Guatemalan schoolchildren. AB - One hundred thirty children (65-95 mo old) from a low-socioeconomic neighborhood of Guatemala City participated in a randomized, double-blind, controlled trial of zinc supplementation. One group received 10 mg Zn/d (n = 65) and the other group received a placebo (n = 65); 90 +/- 9.2 doses were given over 120-150 d. Stools were examined for prevalence and intensity of helminths and prevalence of protozoa at the beginning and end of the study. The initial prevalence was 42% for helminths and 18% for protozoa, with no differences between groups. Mebendazole was administered to all children, and protozoal infections were treated specifically at the beginning of the study. The reinfection rates were 17% (11 of 65) for helminths and 12.3% (8 of 65) for protozoa in the zinc group and 15% (10 of 65) and 10.7% (7 of 65), respectively, in the placebo group (P > 0.05). Analysis by specific parasites revealed no treatment effect. We conclude that neither plasma or hair zinc status nor oral zinc supplementation had an effect on parasite status in children. PMID- 8480686 TI - Effect of chemotherapy on the energy and protein metabolism of children near the end of treatment for acute lymphoblastic leukemia. AB - Eight children in the final 3 mo of chemotherapy for acute lymphoblastic leukemia were studied while on oral 6-mercaptopurine (6MP) maintenance therapy and then again 4-9 mo after chemotherapy had been completed. Six of the eight were also studied a second time while on 6MP in the 24-h period after receiving intravenous methotrexate (MTX). 6MP reduced protein oxidation after a test meal and reduced fasting urinary urea excretion by enhancing the reutilization of endogenous amino acids for protein synthesis. MTX had no detectable effects on protein metabolism but reduced overnight carbohydrate utilization by enhancing fat utilization. A similar enhancement of fat utilization was evident after a test meal. The two drugs in combination resulted in effects on protein and energy metabolism that were the sum of the individual effects plus an increase in the rate of whole-body protein turnover and synthesis. PMID- 8480687 TI - Resting energy expenditure before and after treatment for Pseudomonas aeruginosa infection in patients with cystic fibrosis. AB - To investigate whether metabolic rates change after antipseudomonal treatment, resting energy expenditure (REE) was measured in 29 patients with cystic fibrosis (CF) aged 5-27 y before and after a 2-wk course of intravenous antibiotics for the treatment of chronic Pseudomonas aeruginosa infection. Before therapy, mean (+/- SD) REE was increased to 119.0 +/- 11.4% of the predicted normal value (REE%). Seventeen of the 29 patients were classified as having increased baseline REE% (> 115% of predicted, group I), whereas 12 patients had resting energy expenditures within the normal range (group N). After antipseudomonal therapy, mean REE% decreased significantly by 6.2% of predicted. This decline was negatively correlated with the baseline REE% (r = 0.70, P < 0.001). It was most pronounced (-11.3%) in group I whereas patients of group N showed no major changes. These results suggest that antipseudomonal therapy can reduce increased energy requirements of moderately ill CF patients with chronic Pseudomonas aeruginosa infection. PMID- 8480688 TI - Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases. AB - The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes. PMID- 8480689 TI - Pathogenesis of the fatty liver in protein-energy malnutrition. PMID- 8480690 TI - Zinc metabolism in pregnancy. PMID- 8480691 TI - Serum lipids and arterial blood pressure in relation to waist-to-hip ratio in young males. PMID- 8480692 TI - Nutrition of Alaskan Natives. PMID- 8480693 TI - Crime and punishment. PMID- 8480694 TI - Angle classification. PMID- 8480695 TI - Facial keys to orthodontic diagnosis and treatment planning. Part I. AB - The purpose of this article is twofold (1) to present an organized, comprehensive clinical facial analysis and (2) to discuss the soft tissue changes associated with orthodontic and surgical treatments of malocclusion. Facial examination leads to avoidance of potential orthodontic and surgical facial balance decline and enhances diagnosis, treatment planning, treatment, and quality of results. Patients are examined in natural head position, centric relation, and relaxed lip posture. Nineteen key facial traits are analyzed. By examining the patient in this format, reliable facial-skeletal traits can be recorded that enhance all aspects of care. Orthodontics and surgery used to correct the bite alter facial traits; alteration should reverse negative traits and maintain positive traits. This cannot be achieved without a complete understanding of the face before treatment. Tooth movement (orthodontic or surgical) used to correct the bite can negatively impact facial esthetics, especially if pretreatment esthetics are not defined before treatment. Treating the bite based on model analysis or on osseous cephalometric standards without examination of the face is not adequate. Three questions are asked regarding the 19 facial traits before treatment: (1) What is the quality of the existing facial traits? (2) How will orthodontic tooth movement to correct the bite affect the existing traits (positively or negatively)? (3) How will surgical bone movement to correct the bite affect the existing traits (positively or negatively)? This article is for orthodontists, and yet, much surgical information is included. This is intentional. We only treat what we are educated to see. The more we see, the better the treatment we render our patients. PMID- 8480696 TI - Periodontal tissue response to orthodontic movement of teeth with infrabony pockets. AB - The aim of this study was to evaluate the effect of orthodontic tooth movement on the level of the connective tissue attachment in sites with infrabony pockets. The experiment was carried out in four beagle dogs. The second and fourth premolars were extracted. After healing, angular bony defects were prepared at the mesial aspect of the third premolars. The exposed root surface was scaled and planed, and a notch was prepared at the bottom of the defect. Plaque-collecting cotton floss ligatures were placed around the neck of the teeth and maintained in situ for 3 weeks, followed by an additional 2 months of plaque accumulation before the orthodontic tooth movement was initiated. In each dog, one premolar was moved away from the angular bony defect and one premolar into and through the angular bony defect. The maxillary third premolars served as control teeth and were not subjected to orthodontic tooth movement. After orthodontic treatment (5 to 6 months), the teeth were stabilized for a period of 2 months before biopsy sampling. Clinical, radiographic, and histologic evaluations revealed that it was possible to establish and maintain an infrabony pocket with a subcrestal, plaque induced inflammatory lesion during the entire course of the study. While the control teeth had maintained their attachment levels, all but one of the orthodontically moved teeth showed additional loss of attachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480697 TI - Serum and alveolar bone phosphatase changes reflect bone turnover during orthodontic tooth movement. AB - Acid and alkaline phosphatase changes have been demonstrated histochemically and biochemically during the early stages of an orthodontic tooth movement cycle. However, quantitative data on neither alveolar bone nor serum phosphatase changes over an entire tooth movement cycle have been reported. This study examined acid, tartrate-resistant acid (TRAP), and alkaline phosphatase changes in serum and alveolar bone during an orthodontic tooth movement cycle in 288 adult male Sprague-Dawley strain rats. The effect of differing initial force magnitudes on phosphatase changes was also examined. Data were obtained from four groups: sham control and three treatment groups (20, 40, and 60 gm activations). Each group (n = 72) was subdivided equally into six sacrifice subgroups (1,3,5,7,10, and 14 days). Treated animals received a precisely loaded orthodontic tipping force to the maxillary molars. Phosphatase measures were obtained by colorimetric assays. Analysis of variance (ANOVA) procedures were performed to examine for differences within groups across time and among groups at each time point. Data from treated animals were combined, adjusted for control values, and examined across time to permit comparisons with previously described histomorphometric changes. Analysis of variance indicated no differences occurred in the control group across time. Significant differences in serum values occurred across time within the force groups (p < 0.01), and among force and control groups at various times in both sera and bone (p < 0.05). In the pooled treatment data, a peak in serum acid phosphatase occurred at day 1 and in bone at day 3 (the later mirroring histomorphometric findings) (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480698 TI - Craniofacial morphometry by photographic evaluations. AB - Frontal and lateral oriented profile photographs of 108 healthy young adults (57 men and 51 women) were taken, and a standardized protocol was used to quantitatively describe the depicted craniofacial soft tissue structure, the relationships among facial structures, and head posture relative to the ground. Pictures were taken in two body positions, standing and sitting. The male faces were, on average, wider and longer than the female faces, in both frontal and lateral views, with greater differences in the mouth and chin regions. Both sexes were generally symmetrical. Persons who were asymmetric compensated for their appearance by changing head posture relative to the ground, so that in the frontal plane, the interpupillary axis and the occlusal plane were parallel to the ground. Measurements can be employed in computer graphic reconstructions used in orthognathic, maxillofacial, and plastic surgery. In the standing position, the Frankfurt plane was directed upward and forward, with a mean angle of 13 degrees relative to the ground. In seated subjects, it was more nearly horizontal (5 degrees in the men, 8 degrees in the women). This result confirms the need for a careful reevaluation of standard cephalometric and photographic protocols. PMID- 8480699 TI - Pulpal response to orthognathic surgery: a long-term radiographic study. AB - The purpose of this study was to determine if the ischemia associated with orthognathic surgery causes long-term pathologic changes in the pulp similar to those documented after traumatic injuries. A total of 93 patients, 21.9 to 63.9 years of age (mean 38.5 years, SD 9.4), consented to participate in a follow-up study ranging from 4.7 to 15.3 years (mean 8.9 years, SD 2.9) after surgery. LeFort I osteotomy was performed on 42 patients and bilateral sagittal split osteotomies on 76 patients. Full-mouth series of periapical radiographs taken at the time of follow-up were compared with pretreatment and posttreatment panoramic radiographs. The development of pulp canal obliteration was observed more often in the maxillae of patients treated with LeFort I osteotomy than in those without (p < 0.001). No difference was seen in the frequency of maxillae with teeth developing radiographic signs of pulp necrosis between patients treated with and without LeFort I osteotomy. However, a higher proportion of the teeth were affected among the patients treated with osteotomy (p < 0.01). The presence of a restoration or caries was a risk factor for the development of necrosis (p < 0.01). Bilateral sagittal split osteotomies had no apparent effect on long-term pathologic pulpal changes. No internal resorption was seen. Only very few teeth were extracted during the follow-up period. PMID- 8480700 TI - Recording and measuring malocclusion: a review of the literature. AB - The methods of recording and measuring malocclusion can be broadly divided into two types: qualitative and quantitative. Among the qualitative methods of recording malocclusion, Angle's method of classifying malocclusion with or without modifications is probably the most widely used. The "WHO/FDI Basic Method for Recording of Malocclusion" was published in 1979 to establish an assessment format to determine the prevalence of malocclusion and to estimate treatment needs of a population. Among the many occlusion indices developed by various research workers, the occlusal index developed by Summers appeared to have the least amount of bias, is best correlated with clinical standards and has the highest validity during time. More recently, methods have also been developed to enable assessment of treatment need according to grade index scales. However, experience in using these methods is still very limited. PMID- 8480701 TI - The influence of growth hormone (rhGH) therapy on tooth formation in idiopathic short statured children. AB - The purpose of this preliminary study was to evaluate tooth formation in children with idiopathic short stature, before and during treatment with recombinant growth hormone (rhGH). Twenty-nine short-statured children ages 6 to 13 years were assigned into two treatment groups, an "experimental" group (n = 18), which received rhGH, and a "control" group (n = 11), which was observed for 1 year before commencing rhGH treatment. Clinical and radiographic records were obtained at the initial, year 1, and year 2 visits. Tooth formation and stature were assessed by calculating Z-scores, appropriate for the age and gender of each child. Delta-Z scores, which measure the change in Z-score over time, were also calculated between annual visits. Height was measured and recorded every 3 months, and Z-score statural norms for age and gender were derived from the 1977 National Center for Health Services national probability sampling. Tooth formation standards were derived from Moorrees et al. A matched control sample for tooth development was derived from untreated children. Tooth formation was initially delayed although the degree of reduction in stature exceeded the initial degree of delay in tooth formation. During this 2-year study, rhGH therapy had a significant influence on acceleration or gain in stature, but did not have a significant influence on tooth formation. PMID- 8480702 TI - Patient empowerment: the young patient. AB - The responsibilities that doctors have for their patients often transcend the obvious. When orthodontists begin treatment relationships with young people, they should understand that preadolescent and adolescent patients are very impressionable and educable. This creates the possibility for extraordinary positive experiences during the period of therapy that may be unexpected by the doctor, the professional office staff, the patient, and the patients' families. In the present day climate created by OSHA and barrier techniques, recognition of our potential role is more important than ever. Children will be exposed over an extended time interval to the work of well-trained orthodontists and orthodontic staff. Role modeling and mentoring may occur that could benefit these patients throughout their entire life. New responsibilities that can create a sense of accomplishment and build self-confidence are introduced and accepted. The genesis of this article was the result of a conversation that developed between Mrs. Burnes and me after she had commented about the positive influence that her children's orthodontic therapy had on their general character development. Noting her area of professional expertise, and combining that with my general interest in the subject of personal character development, we decided to commit our thoughts to paper. Our goal was to identify some of the mutually satisfying interactions that can occur between the orthodontist, staff, patient, and parent. PMID- 8480703 TI - Palatal measurements of prematurely born, very low birth weight infants: comparison of three methods. AB - To enable investigation of palatal changes in infants who are prematurely born, it is necessary to first establish a reliable method of measurement of these tiny edentulous palates. This study compared the Olivetti-Inspector machine, Vernier calipers, and stereophotogrammetry for this purpose. Measurements were taken of 12 palatal casts of four infants at prescribed time intervals during the neonatal period. In each of the three methods, measurements were recorded as variables generated in the X and Z axes of the Cartesian scale in relation to three specified points along the Y axis. The results revealed that all methods were comparable, but the Vernier calipers differed significantly from the other two methods in height measurements, (p < 0.001). It was also found that both the Olivetti-Inspector machine and the Vernier calipers consistently underestimated the width, compared with Olivetti-Inspector machine, (p < 0.05). Stereophotogrammetry was found to be the most consistent method of measuring the configuration of preterm infant palates. PMID- 8480704 TI - A mesially impacted mandibular second molar. Treatment considerations and outcome: a case report. AB - The uprighting of an impacted mandibular second molar presents special problems that may require auxiliary appliances and the implementation of "therapeutic diagnosis." In this case, the presence of an ectopically positioned third molar required modification of the original treatment plan. PMID- 8480705 TI - Pneumoparotitis with orthodontic treatment. AB - Self-induced pneumoparotitis has not been commonly associated with orthodontic treatment nor dental treatment in general. However, the patient described previously and the other reported cases demonstrate the distinct possibility that accommodation to appliance irritation by "puffing out" the cheeks could result in parotid swelling. Pneumoparotitis should definitely be considered in the evaluation of patients with parotid swelling, particularly in cases of unexplained swelling with rapid onset. PMID- 8480706 TI - Mock Boards and motivation: the keys to certification by the American Board of Orthodontics. PMID- 8480707 TI - Concern for orthodontic education. PMID- 8480708 TI - Comments on the frontal sinus and mandibular growth prediction. PMID- 8480709 TI - Facial keys to orthodontic diagnosis and treatment planning--Part II. PMID- 8480710 TI - Normalization of incisor position after adenoidectomy. AB - Changes in incisor inclination and position in both jaws of children during the first 5 years after adenoidectomy were studied. The main change is a significant increased labial inclination of the incisors for the adenoidectomy groups. All variables that measure the labiolingual position of the mandibular incisors confirm a significant labial incisor positioning for both sexes. Stepwise regression analysis shows that 41% to 44% of the incisor proclination after adenoidectomy is accounted for by two regressors--sex (female) and increase in the sagittal size of the nasopharynx. The study supports the hypothesis that a changed mode of breathing after adenoidectomy is associated with significant labial positioning of the incisor teeth. PMID- 8480711 TI - Moments with the edgewise appliance: incisor torque control. AB - Traditional edgewise orthodontic mechanics are significantly limited in their ability to provide incisor torque control because of the limitations of bracket to-bracket mechanics and the poorly defined reciprocal actions inherently produced. Attempts to address this issue clinically have been largely empirical. The science of mechanics dictates that all incisor torque control mechanisms must act through one of two basic principles: the moment of a couple or the moment of a force. The torquing arch is a modification of the traditional edgewise system and employs the moment of a couple to achieve incisor torque control and precise definition of reciprocal effects. The torquing arch force system includes a large moment to rotate incisors in a crown facial/root lingual direction, and concurrent equilibrium forces to extrude incisors and intrude molars. Alternatively, the base arch uses the moment of a force to also rotate incisors in a crown facial/root lingual direction. The base arch, however, includes a large moment to rotate molars in a crown distal/root mesial direction, and concurrent equilibrium forces to intrude incisors and extrude molars. Depending on how they are employed, torquing arches and base arches may also rotate molars in a faciolingual direction, enhance or diminish posterior anchorage, and increase or conserve arch perimeter. Contemporary quality orthodontic care requires an awareness and control of all of the forces created by orthodontic appliances. PMID- 8480712 TI - Morphologic and functional implications of the surgical-orthodontic management of mandibular prognathism: a comprehensive review. AB - The aim of this review is to present the various morphologic and functional implications of the surgical-orthodontic management of mandibular prognathism, thus providing a more complete determination of the efficacy of this modality of treatment. Major conclusions that can be drawn from the bibliography indicate that: (1) After treatment considerable improvement takes place on the soft tissue and dentoskeletal profile, occlusal tooth contacts, and temporomandibular joint function and and pain; (2) Surgical management of mandibular prognathism can be associated with decreased maximum interincisal opening; (3) Although immediately after surgery there is a tendency for the condyles to be distracted downward and anteriorly from their preoperative position, in long-term postsurgery the condyles, on the average, regain their initial position; (4) Compensatory alterations in the pharyngeal, suprahyoid, and infrahyoid muscular regions take place postoperatively; (5) Skeletal changes after mandibular setback to correct mandibular prognathism occur frequently, but their magnitude and patterns exhibit variation and are not necessarily detrimental; and (6) Fulfillment of expectations toward surgical-orthodontic management of mandibular prognathism was reported to be frequent. PMID- 8480713 TI - The evaluation of dual cement resins in orthodontic bonding. AB - Dual-cement resins are composite resins that are both light activated and chemically cured. They can be cured completely with a visible light source or by the catalyst and base reaction of the material. With the control of setting time, dual cements appear to offer clinicians advantages in orthodontic bonding. The purposes of the present research are to compare various dual cements in regard to orthodontic bonding and to evaluate them in relation to currently used chemically cured and light-cured composite resins for bonding stainless steel mesh-backed orthodontic brackets. Seven currently available orthodontic bonding systems (three light cured and four chemically cured) and three dual cements were evaluated. Each of the 10 groups contained 15 noncarious mandibular incisors. Mandibular incisor brackets were bonded to the teeth in accordance with the manufacturer's recommendation. After bonding, the teeth were stored for 5 days in water at 37 degrees C. An Instron machine (Instron Corp., Canton, Mass.) was used to test samples. All samples were compared with Concise orthodontic bonding composite (3M, St. Paul, Minn.). The results of this investigation show that it is possible to bond solid, mesh-backed metal orthodontic brackets to teeth with a dual cement. The shear bond strengths of the dual cements, as tested in the laboratory, should be adequate to withstand normal orthodontic forces. Increased control of the setting time of the dual cements will allow the clinician more time to correctly position brackets and to remove excess resin before curing. In addition, the clinician can be assured of complete polymerization with the chemical properties of the dual cement resins. PMID- 8480714 TI - Effects of orthodontics on the facial profile: a comparison of changes during nonextraction and four premolar extraction treatment. AB - Cephalometric radiographs were used to examine soft tissue profiles of 198 orthodontic patients treated with full fixed appliances without extraction of any permanent teeth. Records were selected at random from five sources: cases treated by a Tweed Foundation instructor using the Tweed technique, patients treated with the Begg appliance, patients treated in one of two different practices with pretorqued, preangulated edgewise appliances, and patients treated in two stages with a functional appliance followed by full fixed edgewise appliances. The criteria for selection of cases and the methods of data collection were designed to allow comparisons with data collected by Drobocky and Smith on patients treated with extraction of four first premolars. Although the mean value of soft tissue changes were smaller in the nonextraction patients, the variability of these changes were generally as great as in the four premolar extraction cases. In addition, the percentage of undesirable facial changes was similar in the extraction and nonextraction samples. The results provide additional evidence that it is simplistic and incorrect to blame undesirable facial esthetics after orthodontic treatment on the extraction of premolars. PMID- 8480715 TI - Class II elastics and extractions and temporomandibular disorders: a longitudinal prospective study. PMID- 8480716 TI - A comparison of the rate of space closure using a nickel-titanium spring and an elastic module: a clinical study. AB - A study of the efficiency of space closure after premolar extraction was undertaken, comparing a nickel-titanium closed coil spring and an elastic retraction module by using sliding mechanics along an 0.019 x 0.025-inch stainless steel arch wire in 0.022 x 0.028-inch preadjusted stainless steel brackets. The rate of space closure in 17 subjects was analyzed from study models and was found to be significantly greater and more consistent with the nickel titanium closed coil springs than with the elastic modules, in both arches. There were no clinically observable differences in the tooth positions between the respective techniques. PMID- 8480717 TI - Three-stage activator treatment of a severe skeletal Class II, open bite malocclusion. AB - Activator therapy for a severe Class II, Division 1 malocclusion with open bite malocclusion is described. The treatment was performed in three stages: one, "early-early," at the age of 5 to 6 years; one "early," between 9 and 11 years; this was followed by 2 years of retention with a maxillary retainer. The patient continued to be observed further over a 3-year period. The final records show a normal, stable occlusion, and good facial balance. PMID- 8480718 TI - ABO certification: a worthy goal. PMID- 8480719 TI - Principles of the merge letter. PMID- 8480720 TI - The management of financial assets yield considerations. PMID- 8480721 TI - Cyclosporine and other immunosuppressive agents: current and future role in the treatment of inflammatory bowel disease. PMID- 8480722 TI - Endoscopic surveillance of Barrett's esophagus: another viewpoint. PMID- 8480723 TI - Current treatment modalities for symptomatic gallstones. AB - Gallstone disease is an important clinical problem: approximately 10% of all adults in the western population have gallstones. Most gallstones, however, remain asymptomatic, and from various disciplines there is consensus that only symptomatic gallstones require therapy. Since the first gallbladder extirpation in 1882, cholecystectomy has been considered the gold standard. Nowadays, this operation is performed laparoscopically in most hospitals. Despite relatively low morbidity and mortality rates, a number of alternative therapies have been developed in the past few years. These alternative treatment modalities are especially indicated in high risk patients and in patients rejecting surgery. In this review article, the currently available treatment modalities are discussed. PMID- 8480724 TI - Cyclosporine enemas for treatment-resistant, mildly to moderately active, left sided ulcerative colitis. AB - Ten patients with treatment-resistant left-sided ulcerative colitis were treated in an open protocol with 350 mg cyclosporine enemas nightly for 4 wk. A 12-point clinical disease activity index (DAI) score was calculated at baseline and after 4 wk. Whole blood and colonic tissue cyclosporine concentrations were determined by HPLC at the end of the study. Five of 10 patients responded to treatment, defined as a decrease in the clinical DAI score > or = 3 points. Responders retained the enemas longer than nonresponders (7.5 +/- 1.3 vs. 3.3 +/- 2.2 h, p = 0.01), and there was a positive correlation between decrease in the clinical DAI score and enema retention time (r = 0.64, p = 0.05). The mean colonic tissue cyclosporine concentration was not significantly higher in responders than in nonresponders (2884 +/- 1635 vs. 2359 +/- 576 ng/g, p = 0.52), and the correlation between decrease in the clinical DAI score index and colonic tissue cyclosporine was weak (r = 0.39, p = 0.26). Cyclosporine was undetectable in whole blood samples from all patients, and there were no apparent side effects with treatment. In conclusion, 50% of patients with treatment-resistant left sided ulcerative colitis significantly improved during therapy with cyclosporine enemas for 4 wk. Patients with longer enema retention times were more likely to respond. A controlled trial is underway to investigate these findings further. PMID- 8480725 TI - Rapid closure of Crohn's disease fistulas with continuous intravenous cyclosporin A. AB - Fistulas complicating Crohn's disease often are refractory to medical management. Immunosuppressive therapy is sometimes effective but requires several months before efficacy can be determined. We treated five patients with Crohn's disease complicated by chronic draining fistulas unresponsive to previous surgery, steroids, antibiotics, total parenteral nutrition, 6-mercaptopurine, or azathioprine with continuous infusion cyclosporin A (CyA). The five patients had a total of 12 fistulas (five enterovaginal, three perianal, three enterocutaneous, one enterovesical). CyA was administered initially at 4 mg/kg/day for 6-10 days, after which oral dosing was begun at 8 mg/kg/day and adjusted to maintain trough serum levels of 100-200 ng/ml. All fistulas responded to CyA infusion with decreased drainage and with improvement in both perifistular inflammation and patient comfort. Complete resolution of drainage was seen in 10 of the 12 fistulas. Initial response was seen after a mean of 3.6 days (range, 2 5 days) with complete cessation of drainage in the 10 fistulas after a mean of 7.9 days (range, 3-28 days). Therapy was continued for a mean of 6.2 months (range, 1.5-18 months). Relapse was seen in two perianal fistulas (3 wk and 7 months) and in two enterovaginal fistulas (1 and 2 months). Two of these recurrences corresponded to lowered serum levels of CyA. An enterocutaneous fistula also recurred after 2.5 months, associated with a distal stricture that required resection. Side effects were minor except for a mycotic aneurysm in one patient which occurred after 7 months of treatment. Intravenous CyA may prove to be a useful agent in the initial management of refractory Crohn's disease fistulas, although relapse as serum levels are lowered and infectious complications are limiting factors for long-term use as a single agent. PMID- 8480726 TI - The effect of ethanol on the pancreatic duct sphincter of Oddi. AB - Alcohol ingestion causes pancreatitis to develop in some people, but the mechanism(s) by which alcohol causes pancreatitis are unclear. The effect of alcohol on the pancreatic duct sphincter of Oddi (PD-SO) may play a significant role. To better understand the effects of alcohol on the PD-SO, we studied 24 alcoholic subject's PD-SO before and after 80 g of alcohol was instilled into their stomachs. Seventeen of the subjects had a prior history of pancreatitis. The mean maximal alcohol level achieved by 30 min after the instillation was 98.1 +/- 47.9 mg/dl. The only prealcohol differences between the pancreatitis group and the nonpancreatitis group were higher mean basal PD-SO pressures and higher mean phasic contraction amplitudes (8.7 and 20.2 mm Hg higher, respectively) in the pancreatitis group. The acute change in the subjects' blood alcohol levels produced similar changes in both groups. A non-statistically significant fall in the mean basal PD-SO pressure of 2.7 mm Hg was observed. The phasic contraction mean amplitude decreased by 24.1 mm Hg (p < 0.001) and the mean duration decreased by 0.6 s (p = 0.0064). The frequency of phasic contractions did not change after ingestion of alcohol. There was a significant fall in the percentage of antegrade phasic contractions (-15.8%, p = 0.016), which was compensated for by nearly equal increases in the percentage of retrograde and simultaneous contractions. We conclude that acute alcohol ingestion in subjects with a history of chronic alcohol consumption changes the PD-SO motor activity in a way that could predipose to duodenopancreatic reflux. Thus, reflux of bile, activated enzymes, or other substances into the pancreatic duct might occur more readily and predispose one to pancreatitis after alcohol ingestion. PMID- 8480727 TI - Comparison of simultaneous esophageal pH monitoring and scintigraphy in infants with gastroesophageal reflux. AB - Twenty-nine infants under 1 yr of age were studied by simultaneous esophageal pH monitoring and scintigraphy for evaluation of gastroesophageal reflux (GER). Scintigraphy and pH monitoring were performed for 120 min after infants ingested their usual volume of formula. The number of reflux episodes during six 20-min intervals, as determined by both tests, were recorded. Esophageal pH monitoring was continued for 18-24 h. Sixteen of 29 patients exhibited GER by pH monitoring during the 2-h study. Gastroesophageal reflux occurred in seven of 29 during the first hour and 13 of 29 during the second hour. The mean time of first reflux episode detected by pH monitoring following the feeding was 82.4 +/- 49.3 min. In comparison, 28 of 29 patients had GER by scintigraphy during the 2 h. All 28 exhibited GER during the first hour, whereas only 22 of 29 patients exhibited GER during the second hour. The mean time of first episode of reflux by scintigraphy was 3.1 +/- 2.7 min. Forty-five percent of all reflux episodes detected by scintigraphy occurred during the first 20 min and 80% were detected during the first hour. In contrast, only 17% of reflux episodes were seen by pH monitoring during the first 20 min and 35% during the first hour; 65% of reflux episodes detected by pH monitoring were during the second hour. There was no correlation between the total number of reflux episodes detected by scintigraphy and 2-h esophageal pH monitoring during the 2-h study period (r = 0.326; p > 0.1). Overall, to detect reflux, scintigraphy was a more sensitive method than esophageal pH monitoring under the conditions of this study. Scintigraphy selectively detected reflux during the first 60 min post-prandially whereas pH monitoring was more likely to detect reflux beyond the first postprandial hour. These observations help to explain the lack of correlation between the two tests. PMID- 8480728 TI - Effect of age and bolus variables on the coordination of the glottis and upper esophageal sphincter during swallowing. AB - We studied 1) the effect of age and bolus variables on a) the coordination of deglutitive vocal cord adduction and upper esophageal sphincter (UES) relaxation and b) the duration of deglutitive vocal cord adduction; 2) the effect of the presence of a manometric catheter across the UES on the deglutitive glottal function; and 3) the temporal relationship between deglutitive vocal cord closure and swallow-induced apnea. We studied 10 young (23 +/- 2 yr) and 10 healthy elderly (73 +/- 2 yr) volunteers by concurrent videoendoscopy, UES manometry, respirography, and submental surface electromyography. In both groups the onset of vocal cord adduction preceded the onset of UES relaxation, deglutitive apnea, and submental electromyogram swallowing signal. In both groups, bolus volume and temperature did not have any significant effect on the duration of deglutitive vocal cord adduction. In both young and elderly volunteers, water swallows, compared with dry swallows, significantly shortened the interval between the onset of deglutitive vocal cord adduction and the onset of UES relaxation. In conclusion, coordination between deglutitive glottal and UES function, as well as the duration of deglutitive vocal cord adduction, is preserved in the elderly. Bolus volume and temperature do not have a modulatory effect on the duration of vocal cord closure, but water swallow shortens the interval between the onset of glottal closure and UES relaxation. This shortened interval may contribute to the safety of the airway during swallowing of liquid volumes. PMID- 8480729 TI - Magnetic resonance imaging and localized in vivo proton spectroscopy in patients with fulminant hepatic failure. AB - Magnetic resonance imaging (MRI) and in vivo proton spectroscopic changes in the brain in three patients with fulminant hepatic failure are described. MRI showed cerebral atrophy in two and changes somewhat similar to what have been described in chronic hepatic encephalopathy. MR spectroscopy showed low myoinositol with high glutamine in grade IV coma, which returned to normal as patient showed clinical recovery. We conclude that these techniques will be useful in understanding the complex pathophysiology of fulminant hepatic failure. PMID- 8480730 TI - Does co-prescription of sucralfate with ranitidine therapy enhance the healing of gastric ulcers? AB - It has been suggested that the co-administration of ranitidine and sucralfate may enhance peptic ulcer healing more than administration of either drug alone. This study compared the frequency of healing of gastric ulcers treated with either ranitidine 300 mg nocte plus sucralfate 1 g tds or with ranitidine 300 mg nocte plus placebo. Patients (n = 259) were treated initially for 4 wk, and this period was extended to 8 wk for those patients whose ulcers had not healed. Ulcer healing and patient symptom data were assessed at 4 and 8 wk, whereas patients recorded the presence of ulcer pain on a daily basis. Ulcer healing rates were 63% and 66% at 4 wk, and were 93% and 91% at 8 wk, in the ranitidine-plus sucralfate group and the ranitidine-plus-placebo group, respectively. Both treatments were equally effective in relieving symptoms. Thus, combination therapy with sucralfate provided no additional benefit over treatment with ranitidine alone. PMID- 8480731 TI - Esophageal manometry in children with esophagitis. AB - Esophageal motility was studied in 31 patients with mild to moderate esophagitis and in 48 patients without esophagitis to determine the effect of esophageal inflammation on lower esophageal sphincter pressure, and the amplitude, duration, and velocity of esophageal contractions. There were no significant differences in any of these parameters associated with esophageal inflammation. We conclude that mild to moderate esophagitis does not cause serious esophageal dysfunction in children. PMID- 8480732 TI - NSAID-induced gastric ulceration is dose related by weight: an endoscopic study with flurbiprofen. AB - Numerous studies have shown that higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased levels of mucosal injury and ulceration in both normal volunteers and patients. The present dose-ranging study was designed to determine whether escalating doses of a commonly prescribed NSAID, flurbiprofen, when expressed as mg/kg dosages, were associated with increased mucosal injury and ulceration. Subjects received either the recommended dose of 300 mg/day of flurbiprofen (N = 10), or the higher than recommended doses of 400 mg/day (N = 20) and 500 mg/day (N = 10), for a period of 7 days. Endoscopic examination was performed on day 0 and day 7, and the stomach was evaluated on day 7 for mucosal injury on a 0-4 scale, and for the presence or absence of ulcer. One gastric ulcer was seen in each of the 300- and 400-mg groups. However, in the 500 mg/day group, four gastric ulcers were seen (40%) (p = 0.04). Three of the six subjects developing gastric ulcer were of a fairly low body weight (two women, one man), and when the data were analyzed on a mg/kg basis, all six ulcers occurred in 19 of the 40 subjects receiving > 5.95 mg/kg, whereas no gastric ulcers were seen in the 21 subjects receiving dosages below that level (p < 0.01). These data suggest that, at least for this agent, a threshold level may exist above which gastric ulcers are much more likely to occur. This may in part explain why elderly debilitated, low-body-weight female patients are more prone to NSAID-related gastric ulcer. PMID- 8480733 TI - Helicobacter pylori prevalence in acquired immunodeficiency syndrome. AB - Helicobacter pylori is consistently reported with high prevalence in HIV-negative patients with chronic gastritis and active ulcer disease. This study is an evaluation of the prevalence of H. pylori in AIDS patients, and the association with chronic gastritis, erosions, and ulcer disease. Seventy-three AIDS patients referred for the evaluation of gastrointestinal symptoms underwent upper endoscopy and antral gastric biopsy. Histologic gastritis was diagnosed and degree of activity graded on hematoxylin-eosin stain. H. pylori organisms were identified by acridine orange stain. A single pathologist evaluated the biopsy specimens. H. pylori was found in 15% (11 of 73) of AIDS patients. Histologic chronic active gastritis was evident in 94.5% (69 of 73) of the study group. H. pylori was identified in 15.9% (11 of 69) of biopsy specimens with histologic chronic active gastritis. The organism was more common in biopsy specimens with a higher grade of activity in the chronic gastritis. Endoscopic erosions or ulcers were noted in 11 patients (seven gastric, four duodenal). H. pylori was present in 18% (2 of 11) of AIDS patients with erosions or ulcers. The prevalence of H. pylori in AIDS patients with histologic chronic active gastritis is much lower than the prevalence previously reported for HIV-negative patients with similar pathology. The low prevalence observed does not implicate H. pylori as the causal agent in most chronic active gastritis in the AIDS population. Impaired acid secretion may reduce colonization of gastric mucosa and explain the low rate of H. pylori observed. PMID- 8480734 TI - Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. AB - The effect of ursodiol on the clinical and biochemical features, serum, urinary, and biliary bile acids was investigated over a 2-yr treatment period in 14 patients with primary biliary cirrhosis (stages II-IV). Pruritus and fatigue improved, and alkaline phosphatase and liver transferases declined significantly in all patients during therapy. In four patients, less inflammation was noted by liver biopsy after 2 yr, but histology of disease did not change. Serum and urinary bile acids were increased several-fold before treatment, with cholic acid predominating. Ursodiol accounted for 30% of biliary bile acids after administration (gallstone subjects approximately 50%), and was conjugated with glycine and taurine in a ratio of 7.3:1. However, in the endogenous bile acids, the ratio increased from 1.2:1 to only 2.1:1. About 6% unconjugated bile acids were secreted into the bile (healthy controls < 1%). Thus, in patients with primary biliary cirrhosis, a larger fraction of free bile acids and a higher proportion of taurine-conjugated bile acids are secreted into the bile, compared with healthy controls. Ursodiol improves symptoms and histology with lower biliary enrichment with this bile acid. PMID- 8480735 TI - The role of neopterin in assessing disease activity in Crohn's disease: classification and regression trees. AB - Neopterin, a product of human monocytes/macrophages stimulated by gamma interferon, was previously found to be correlated with clinical activity of Crohn's disease. The present investigation attempted to identify more precisely the role of neopterin for assessment of clinical activity in a multivariate setting. A broad panel of clinical and laboratory variables was obtained on 76 patients. Neopterin was determined in urine by high performance liquid chromatography. Using a 4-point clinical activity score as dependent variable, multivariate linear discriminant analyses were performed in order to identify subsets of statistically independent laboratory activity indices. Neopterin was shown to be an independent indicator for clinical activity. The significant variables were then tested together with the eight constituent variables of the Crohn's Disease Activity Index. The resulting model, which consisted of the three laboratory variables--erythrocyte sedimentation rate, serum protein and neopterin, together with pain score--was further subjected to two multivariate techniques for comparison: polychotomous logistic regression analysis and the technique of classification and regression trees. By all methods, neopterin was included into the multivariate models, confirming that its determination aids in the assessment of clinical activity in Crohn's disease. PMID- 8480736 TI - Endogenous sex hormones and cholesterol gallstones: a case-control study in an echographic survey of gallstones. AB - In a population survey of gallstones, the serum levels of hormones of the pituitary-gonadal axis and the sex hormone-binding globulin (SHBG) were compared in subjects with cholesterol gallstones and in a control group. In 84 subjects who entered the survey, echographic gallstones that had been identified at the survey, turned out to be radiolucent or mixed (predominantly of cholesterol) at subsequent x-ray. The controls were without gallstones at echography, matched to the cases for potential confounders of the association sex hormones cholelithiasis. Testosterone (T) 17-beta-estradiol (E2), 17-OH progesterone (P), and SHBG were dosed by radioimmunoassay; follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (Prl) by dissociation-enhanced lanthanide fluoro immunoassay (DELFIA). Men with gallstones had lower LH than controls (n = 34, median difference = -0.62 mU/ml, 95% confidence interval (CI) -1.20 to -0.26 mU/ml, paired sign test, p = 0.003). Premenopausal women in the luteal phase of the menstrual cycle with gallstones had higher E2 than controls (n = 7, median difference: +117, pg/ml, 95% CI: +10 to +218 pg/ml, p = 0.008). Postmenopausal women had lower LH than controls (n = 35, median difference = -4.57 mU/ml, 95% CI -9.5 to -1.0 mU/ml, p = 0.04). No other hormones showed statistically significant differences between cases and controls, in either males or females. The findings of this exploratory study in subjects with radiolucent and mixed gallstones suggest that men and postmenopausal women have lower LH, and premenopausal women in the luteal phase of the cycle have higher E2, than controls. PMID- 8480737 TI - The relationship of plasma polyunsaturated fatty acid deficiency with survival in advanced liver cirrhosis: multivariate analysis. AB - Total plasma fatty acids were measured in 101 cirrhotic inpatients (64 men, 37 women, aged 64.3 +/- 1.2 (SEM) yr; range, 34-80) who were subsequently followed for survival for a mean of 14.8 +/- 1.0 months. Data on plasma fatty acids have been published elsewhere. Individual values of these variables were categorized in a binary fashion using the 5th or the 95th percentiles of a group of 44 well nourished healthy controls (24 men, 20 women, aged 51.3 +/- 2.1 yr; range, 32-76) as the cutoff limit. Forty-nine patients died during follow-up (2-yr cumulative probability of survival, 52%). Deficiency of palmitate, dihomo-tau-linolenate, and arachidonate (values below the 5th percentile) were univariately associated with death (long-rank test). However, after a multivariate analysis (Cox's proportional hazards regression), only the existence of plasma arachidonate deficiency was included in the final model (beta, 0.62; relative risk, 1.86; 95% CI, 1.06-3.25; p < 0.05). We conclude that arachidonic acid deficiency significantly increases the mortality risk in patients with advanced liver cirrhosis. PMID- 8480738 TI - Intrahepatic portosystemic venous shunt: diagnosis by color Doppler imaging. AB - Intrahepatic portosystemic venous shunt is a rare clinical entity; only 33 such cases have been reported. It may be congenital, or secondary to portal hypertension. Five patients with this disorder are presented, each of whom was diagnosed by color Doppler imaging, including waveform spectral analysis. One patient with clinical evidence of cirrhosis and portal hypertension had episodes of hepatic encephalopathy and elevated blood levels of ammonia. This patient had a large tubular shunt between the posterior branch of the portal vein and the inferior vena cava. Shunts of this type are considered to be collateral pathways which develop in the hepatic parenchyma as a result of portal hypertension. The other four patients had no evidence of liver disease, and all four evidenced an aneurysmal portohepatic venous shunt within the liver parenchyma. Shunts of this type are considered congenital. The diagnosis of intrahepatic portosystemic venous shunts was established by color Doppler imaging, which demonstrated a direct communication of color flow signals between the portal vein and hepatic vein, in addition to the characterization of the Doppler spectrum at each sampling point from a continuous waveform signal (portal vein) to a turbulent signal (aneurysmal cavity), and finally, to a biphasic waveform signal (hepatic vein). As demonstrated by the five patients, color Doppler imaging is useful in the diagnosis of an intrahepatic portosystemic hepatic venous shunt, and the measurement of shunt ratio may be useful in the follow-up and determining the therapeutic option. PMID- 8480739 TI - Results of a multicenter trial using a mechanical lithotripter for the treatment of large bile duct stones. AB - A prospective, uncontrolled trial of the use of a prototype mechanical lithotripter was performed in 116 patients at nine centers. Standard endoscopic approaches had failed to remove all stones, primarily because of large size (80% of patients). For 92% of patients, common bile duct stones were successfully captured and fragmented following the use of this lithotripter. The frequency of pancreatitis and hemorrhage was no greater than with standard endoscopic retrograde sphincterotomy, and complications unique to lithotripter use were not noted. For endoscopists skilled in therapeutic duodenoscopy, this modality should be considered in management of common bile duct stones refractory to standard techniques. PMID- 8480740 TI - Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease. AB - Aspartame is an artificial sweetener completely metabolized in the gut and absorbed as aspartate, phenylalanine, and methanol. Phenylalanine is thought to mediate or exacerbate hepatic encephalopathy, and an impaired liver may not be able to cope with the ammoniagenic properties of the amino acid constituents, or adequately metabolize methanol. Thus, we compared the clinical and biochemical effects of a single ingestion of aspartame (15 mg/kg) to skim milk (phenylalanine content equimolar to aspartame) and placebo in patients with chronic, alcoholic liver disease in a randomized, crossover study. Aspartame produced an elevation of plasma phenylalanine significantly greater than milk and placebo (Cmax 14.55 +/- 7.38, 10.95 +/- 4.95, 8.84 +/- 4.55 mumol/dl, respectively; p < 0.01). However, quantified encephalopathic changes were observed only with milk (p < 0.05). Plasma aspartate, methanol, formate, and ammonia levels remained unchanged after all treatments. The lack of clinical derangements in encephalopathic indices, methanol accumulation, or biochemical changes in liver status suggests that a single large dose of aspartame (representing 5 times the average daily intake of adults) may be used safely by patients with chronic, stable liver disease. PMID- 8480741 TI - Abdominal tuberculosis: still a potentially lethal disease. AB - The findings in a 4-yr survey of 82 patients with abdominal tuberculosis are described and compared with those encountered in previous surveys. Fourteen cases of intestinal, 11 of mesenteric-lymphnodal, and 57 of peritoneal tuberculosis were identified. The disease occurred essentially in patients living under worsening socioeconomic conditions, and 51 of them had associated pulmonary tuberculosis. Symptoms and clinical findings were again nonspecific, but newer imaging, endoscopic, and other invasive procedures were helpful in establishing a definite diagnosis. In addition, adenosine deaminase determination showed great promise as a noninvasive diagnostic procedure in patients with tuberculous ascites. The six hospital deaths in the series highlight the hazard of potentially lethal delays in early diagnosis and treatment, even in centers with a high awareness of the disease. PMID- 8480742 TI - Plasma acetate levels in a group of obese diabetic, obese normoglycemic, and control subjects and their relationships with other blood parameters. AB - Acetate is a short-chain fatty acid derived from colonic fermentation of carbohydrate and dietary fiber, and from endogenous glucose and fatty acid metabolism in the liver. An impaired acetate metabolism has been reported in diabetic subjects. The aim of the study was to evaluate plasma acetate levels in a group of obese diabetic subjects, compared with obese normoglycemic subjects and normal control subjects. Eleven noninsulin-dependent diabetic patients taking oral antidiabetic drugs, eight obese normoglycemic subjects, and seven control subjects were studied. Liver, kidney, and gut functions were normal in all subjects. Blood acetate, glucose, insulin, and C-peptide were evaluated in all subjects. Acetate levels were significantly higher in the diabetic subjects than in obese normoglycemic and normal subjects. Significant correlations between HbA1c, glucose, and acetate levels, but not between acetate and C-peptide or insulin, were also observed. PMID- 8480743 TI - Acute pancreatitis presenting with visual disturbance. AB - Retinopathy is a rarely recognized complication of acute pancreatitis. We review the literature on this condition and report a case in which the manifestations of retinopathy dominated the clinical picture, initially diverting attention away from the presence of pancreatic disease. PMID- 8480744 TI - Fluoxetine treatment of depression caused by interferon-alpha. AB - Interferon-alpha is the only approved and effective treatment for hepatitis C. Psychiatric side effects are common and have frequently required a decrease in dose or discontinuation of therapy. We here report a case of interferon-alpha induced depression in a 40-yr-old man with hepatitis C successfully treated with the antidepressant fluoxetine, which allowed completion of interferon treatment. PMID- 8480745 TI - AIDS-related hepatic Kaposi's sarcoma: massive bleeding following liver biopsy. PMID- 8480746 TI - Efficacy of the somatostatin analog octreotide in the treatment of two patients with refractory diabetic diarrhea. AB - Two patients with severe refractory diabetes-related diarrhea are described. One patient had steatorrhea. Both responded to octreotide during a mean follow-up period of 7 months. The pathophysiology of diabetic diarrhea and the potential mechanism of action of octreotide are discussed. The only adverse side effect reported was hypoglycemia in one of the patients, which required a reduction of the insulin dose. Octreotide is a safe and effective agent for the treatment of refractory diabetic diarrhea. PMID- 8480747 TI - Failure of piezoelectric lithotripsy of a gallstone impacted in the gallbladder neck. AB - Failure of extracorporeal shockwave lithotripsy is most frequently related to total stone mass, the size of individual stones, or unrecognized stone calcification which interferes with the dissolution effects of orally administered bile salts. We report a case of piezoelectric extracorporeal shockwave lithotripsy failure in a young woman with a 2-cm stone impacted in the neck of the gallbladder. Despite adequate positioning of the shockwave focal point on two separate occasions, no fragmentation was achieved. The stone was subsequently retrieved after the woman underwent laparoscopic cholecystectomy. When treated ex vivo, the stone rapidly fragmented. We hypothesize that the impacted stone, lacking a uniform liquid interface, failed to fragment because of the inability of cavitational forces to achieve a surface effect. PMID- 8480748 TI - Normal serum alkaline phosphatase: an unusual finding in early suppurative biliary obstruction. PMID- 8480749 TI - Acute liver failure due to non-Hodgkin's lymphoma. AB - Acute hepatic failure secondary to involvement of the liver by hematologic malignancies is a very uncommon condition, and usually has a fatal prognosis. We describe the case of a woman who developed acute hepatic failure due to infiltration by a non-Hodgkin's lymphoma 18 yr after the initial diagnosis of a nodular-type lymphocytic lymphoma, while she was apparently in remission. Early diagnosis was achieved through liver biopsy; therefore, rapid administration of chemotherapy allowed her complete recovery. Hepatic biopsy may provide a diagnosis in patients in whom the etiology of liver failure is unknown, thus establishing the possible need for specific treatment. PMID- 8480750 TI - Upper gastrointestinal hemorrhage preceding development of Bouveret's syndrome. AB - Gastric outlet obstruction by a gallstone is a very uncommon clinical entity; it was first reported by Bouveret in 1896. In the patient presented, we were able to show the development of formation of the bilioenteric fistula with massive arterial bleeding from the eroded cystic artery until duodenal occlusion. The process was endoscopically and radiologically observed and documented. Although the diagnosis was made immediately, the patient had to undergo surgery because the gallstone proved to be too large to be extracted endoscopically. PMID- 8480751 TI - The irritable bowel syndrome: in your dreams? PMID- 8480752 TI - Esophageal carcinoma and achalasia: another call for screening? PMID- 8480753 TI - Posttransplant biliary complications: management menagerie. PMID- 8480754 TI - Heatstroke and its manifestations. PMID- 8480755 TI - Change in the histologic type of gastric carcinoma. PMID- 8480756 TI - Ischemic hepatitis. PMID- 8480757 TI - Re: Chronic non-B, non-C hepatitis: report from Pakistan. PMID- 8480758 TI - Colonoscopy to the cecum: how often do we get there? Experience in a community hospital. PMID- 8480759 TI - Colonic obstruction due to anospasm from a thrombosed hemorrhoid mimicking colonic pseudoobstruction in a frail and elderly patient. PMID- 8480760 TI - Presedation intravenous hydrocortisone to reduce diazepam-induced phlebitis. PMID- 8480761 TI - Pulmonary fat emboli associated with acute fatty liver of pregnancy. PMID- 8480762 TI - Successful Helicobacter pylori eradication: a systemic effect of antibiotics? PMID- 8480763 TI - Rectus sheath abscess in Crohn's disease. PMID- 8480764 TI - Gastric ulcer penetrating to the liver: endoscopic diagnosis. PMID- 8480765 TI - The effect of vibro-acoustic stimulation on fetal behavioral state organization. AB - During the third trimester of pregnancy there is a gradual development of fetal behavioral states. These states are distinct and discontinuous modes of neural activity; they reflect a certain degree of maturity and/or integrity of the fetal brain and are homologous with those seen in newborn infants. Abnormal state development has been found in growth retarded fetuses and in fetuses of women with type-1 diabetes. Behavioral state organization is not easily influenced by external factors and most stimuli fail to induce a state change when the fetus is in quiet sleep (state 1F). However, fetuses do react to vibro-acoustic stimulation (VAS) with an electronic artificial larynx. This stimulus induces excessive fetal movements, prolonged tachycardia, disorganization of behavioral states, and state transitions normally not seen in healthy fetuses. The backgrounds for these excessive and unusual reactions are largely unknown. For the time being, it seems better not to use this device in clinical practice. In this review paper, data on the development of behavioral states and on fetal reactions to VAS are discussed. PMID- 8480766 TI - Work in pregnancy. AB - Pregnant women in the western world are increasing their part in paid employment. This can be added to their work in the home which, with their leisure and athletic activities, might add up to a considerable load; the possible effects this exertion could have on the woman and her unborn child has been realized only in the last twenty years and many attempts have been made to quantify it. The patterns of work in the home, in employment, and at sporting activity are assessed. There are two distinct areas of possible influence on the fetus: the work with its physical effort might affect respiratory and metabolic acid-base balance and specific teratogens related to activity at work may be encountered and act at nodal points during fetal growth at specific times, causing congenital abnormalities of organs. Potential hazards under chemical, physical, and biological headings are considered, while both the psychological and physical effect of energy expenditure are discussed. Possible measures of outcome are assessed and three recently published studies from the U.S. and U.K. are examined to show the difficulties of making valid measurements about the effect of work on the pregnancy, as well as that of pregnancy on the work. It is probable that ordinary work done by a fit young woman has no serious effect on herself or a healthy fetus. Research will continue, for it may be that with an impaired afferent nutrition and oxygen supply to the fetus, certain specific increases in degrees of work could have an exaggerated effect. PMID- 8480767 TI - The biomechanics of vibration and low back pain. AB - This work is a review of the mechanical factors related to low back pain production in a vibration environment. The sitting posture is an extreme orientation for the lumbar intervertebral disc that 1) increases its internal pressure, 2) increases its anteroposterior shear flexibility, while: 3) decreasing its resistance to buckling instability and 4) stressing the posterior region of the disc. Vibration is an additional mechanical stressor. Several studies suggest that the following preventive measures be taken to reduce the risk of low back pain due to driving: 1) minimize the vibration reaching the driver, 2) avoid lifting or bending immediately following driving, and 3) walk around for a few minutes following driving. PMID- 8480768 TI - Selected health risks caused by long-term, whole-body vibration. AB - The problem of a "vibration disease" caused by low-frequency whole-body vibration (wbv) is critically discussed. Disorders of the nervous, circulatory, and digestive systems are interpreted not to be predominantly wbv-specific, but to be related to the totality of working conditions. Long-term wbv exposure can probably contribute to the pathogenesis of disorders of female reproductive organs (menstrual disturbances, anomalies of position) and disturbances of pregnancy (abortions, stillbirths). Animal experiments suggest harmful effects on the fetus. WBV has a minor synergistic effect on the development of noise-induced hearing loss. Degenerative changes of the spine are more prevalent among wbv exposed workers. Model calculations demonstrate an increased spinal load in pregnant women exposed to wbv or self-induced vibration, and illustrate a possibility for the comparison of data on stress, strain, and strength. The analysis of individual exposure-effect relationships is suggested as a future approach for evaluating potential occupation-related diseases. PMID- 8480769 TI - Asbestos fiber type in malignant mesothelioma: an analytical scanning electron microscopic study of 94 cases. AB - Although the association between asbestos exposure and malignant mesothelioma is indisputable, controversy continues regarding the relative contribution of the various types of asbestos fibers to the development of mesothelioma. We examined the types of asbestos fibers recovered from lung parenchyma in more than 90 cases of malignant mesothelioma from the United States, using an analytical scanning electron microscope. Almost half of the patients were former asbestos insulators or shipyard workers. The fibers were recovered from lung tissues obtained at autopsy or surgical resection by means of a sodium hypochlorite digestion procedure. Amosite asbestos was identified in 81% of the cases and accounted for 58% of all fibers 5 microns or greater in length. Tremolite/actinolite/anthophyllite were identified in 55% of the cases and accounted for 10% of all fiber types. Chrysotile was identified in 21% of the cases and accounted for 3% of fibers exceeding 5 microns in length. Crocidolite was found in 16% of the cases and accounted for 3% of fibers exceeding 5 microns in length. Nonasbestos mineral fibers (commonly found in the lungs of the general population) were observed in 71% of the cases and accounted for 25% of all fibers 5 microns or greater in length. The findings in this study are at odds with the assertion that crocidolite asbestos is responsible for most mesotheliomas in the United States. PMID- 8480770 TI - Mortality of professional chemists in England and Wales, 1965-1989. AB - Several studies on the mortality of chemists have revealed a lower overall mortality but an excess of deaths from certain diseases, in particular, cancers. This study determined the causes of mortality of 4,012 chemists among 14,884 members of The Royal Society of Chemistry who were followed for a period of 25 years. The results demonstrated consistency with other studies. There was an overall low mortality rate, with fewer deaths than expected from cancers, but an excess mortality from lymphatic and hematopoietic cancers, in particular leukemias. There was an excess of deaths from certain gastrointestinal cancers. There was reduced mortality from respiratory diseases, including lung cancers, and from cardiovascular disease. New findings reported in this study are increased mortality from cancers of the duodenum and kidney, certain skin cancers, mental disorders, and diseases of the nervous system. PMID- 8480771 TI - Validity of exposure in one job as a surrogate for exposure in a cohort study. AB - Frequently, information pertaining to only one job is available or used to evaluate risk estimates of disease in occupational epidemiologic research. The amount of misclassification that such a practice could create has not, however, been examined. We used data from a mortality study of workers employed in 10 formaldehyde-producing or -using plants to address how closely several parameters of exposure based on the first, longest, or last job held in a company compared with those based on the worker's entire employment history at the plant. The best predictor for cumulative formaldehyde exposure at the plant was the longest job at that plant, with a correlation coefficient (r) of 0.70. The correlation with average exposure over the worker's employment was 0.77 for the first job and 0.74 for the longest and last jobs. Peak exposures and highest exposure levels experienced in the plant were more closely related to the first job (r = 0.72 and r = 0.74). The highest correlation with any of the measures was never with the last job. Variation between plants for each of these comparisons, however, was wide. These findings indicate that the use of a single job as a surrogate for exposure received at a particular worksite can result in different degrees of misclassification for different exposure measures. Even though the correlations were generally high, the associated misclassification of exposure could lead to a substantial underestimation of the relative risks in some situations. In this report two hypothetical examples show what effect the misclassification rates could have on estimates of disease risks. PMID- 8480772 TI - Methodology in industrial health studies: Social Security disability data and the medical care system. AB - This paper is directed at the exploration and development of the Social Security data, in the ascertainment and evaluation of industrial health effects. The focus of the study is on disability data, as a national uniform means to identify illnesses and disease that occurred prior to death, that were not recorded on the death certificates. A cohort of employees of an industrial company was processed through the Social Security System to simultaneously identify the disability and death claims that were filed. The total number of white males that filed disability claims was 1,333 and for white females 278. The total number of claims filed for the white males was 1,734 and for white females 382. Comparisons were made of all causes of disability with all causes of death for white males and white females. A remarkably high percentage of causes of disability were not recorded or available by death certificate for ICD categories of diseases and specific cancer sites. The study also demonstrated that disability data contribute significantly to the confirmation of the diagnosis for the cancer sites. The development of the methodology linking Social Security data on disability, medical care, and mortality with industrial medical and environmental exposure data in epidemiological studies is discussed. PMID- 8480773 TI - Upjohn pharmacist reimbursement programs halted by FDA. PMID- 8480774 TI - Heparin lock flush solution versus 0.9% sodium chloride injection for maintaining patency. PMID- 8480775 TI - Providing pharmaceutical services through a pharmacy management company. PMID- 8480776 TI - Asking for more help. PMID- 8480777 TI - Importance of following instructions when compounding. PMID- 8480778 TI - Results of a brown-bag day. PMID- 8480779 TI - Follow-up to coverage of nurse practitioner prescribing bill in California. PMID- 8480781 TI - Insurance that isn't. PMID- 8480780 TI - Marketing practices and health care costs. PMID- 8480782 TI - Implementation of a hospital policy for health care workers exposed to hepatitis or the human immunodeficiency virus. AB - Implementation of a hospital policy for health care workers exposed to the human immunodeficiency virus (HIV) or hepatitis is discussed, using a model program established by San Francisco General Hospital (SFGH). Occupational Safety and Health Administration (OSHA) guidelines on blood-borne pathogens require a comprehensive program for management of occupationally exposed workers at all health care institutions. To meet the need of immediate assessment, SFGH has established a 24-hour hotline staffed by several clinicians. These clinicians provide risk assessment at the time of the call, and the 24-hour pharmacy service, using an anonymous system to protect the worker, can have zidovudine prophylaxis available within five minutes for workers potentially exposed to HIV. Hepatitis prophylaxis focuses on hepatitis B immunization and administration of hepatitis B immune globulin to workers who have been exposed. Ongoing medical management involves monitoring the adverse effects of zidovudine, ensuring that workers receive any workers' compensation benefits to which they are entitled, providing pretest and posttest counseling for exposed workers and their significant others and families, and supplying appropriate documentation. Confidentiality is essential for worker participation in the program. The costs of such a program are not insignificant but must be borne by the institution if it is to take care of its health care workers. Institutional policies and procedures must address all the components of postexposure management, as well as the issues related to HIV- and hepatitis B-infected health care workers. Sufficient staffing and funding, confidentiality, and prevention are the keys to a successful program. PMID- 8480783 TI - Health center-supplier team approach to solving i.v. equipment problems. AB - A team approach to problem solving in which a health care center and a supplier worked together to improve product quality is described and a detailed example is provided. When the health care center began using a new supplier for i.v. solutions and equipment, the supplier's incomplete product line and recurrent functional problems with products led to dissatisfaction of staff members. The supplier suggested that the health care center and supplier form a quality action team. The team addressed eight product concerns by using a total quality management process. For each concern, the team defined the problem and formulated a problem statement, collected data and determined the contributing factors to the problem, developed an action plan for solving the problem, and executed the plan and monitored its impact. After the first meeting, the team met monthly to monitor progress and discuss new ways they could work together to improve product quality and reduce costs. The implementation of the action plans allowed the health care center to realize cost savings and increased staff members' satisfaction with the supplier's products. A quality action team, composed of representatives from a health care center and one of its suppliers, used a total quality management process to solve problems to the satisfaction of both sets of participants. PMID- 8480784 TI - Pharmacy-managed, weight-based heparin protocol. AB - A revised protocol for heparin therapy, in which dosing was based on the patient's weight and the pharmacy staff assumed responsibility for management of the treatment protocol, was evaluated. A fixed-dose protocol for heparin therapy, in which an initial loading dose and infusion rate were specified by physicians and partial thromboplastin times (PTTs) were determined every 12 hours, was revised to determine dosing based on patient weight and diagnosis and to include more levels of dose adjustment and additional laboratory tests. Data on demographic characteristics of patients, heparin therapy, laboratory monitoring, conversion to warfarin therapy, and protocol management were collected for the patients receiving heparin under the revised protocol. Results were compared with those obtained for the old, fixed-dose protocol, which was managed by nursing staff. The revised protocol showed improvements in heparin therapy according to commonly accepted treatment criteria, including dosages, time to achieve a PTT associated with therapeutic anticoagulation, and the time a patient was in the target PTT range. The new protocol was also significantly more effective in avoiding low as well as high PTT ratios. The laboratory monitoring mandated by the revised protocol enhanced the monitoring of heparin therapy, and pharmacy management improved the accuracy and documentation of heparin therapy. Under the revised protocol, anticoagulation goals were attained more rapidly, and dosing changes were more likely to be correct and appropriately documented. PMID- 8480785 TI - Stability of midazolam hydrochloride in parenteral nutrient solutions. AB - The compatibility and stability of midazolam hydrochloride in three parenteral nutrient (PN) solutions and the stability of 15 amino acids in the presence of midazolam hydrochloride were studied. Six combinations of three PN solutions with amino acid concentrations of 1.5%, 2.5%, and 5% and two midazolam concentrations (0.1 and 0.5 mg/mL) were prepared in triplicate and stored at room temperature under normal fluorescent lighting. Duplicate samples were visually inspected for color change, precipitation, or gas formation and tested for pH. The samples were evaluated for midazolam and amino acid content by high-performance liquid chromatography at zero, one, three, and five hours. Midazolam and amino acid concentrations did not change significantly during the study. There was no evidence of color change, precipitation, or gas formation with any midazolam-PN solution combination when the combinations were examined visually and under a microscope, and no substantial changes in pH occurred. Midazolam 0.1 and 0.5 mg/mL (as the hydrochloride salt) was stable in the three PN solutions studied; in addition, the amino acids present in the 1.5%, 2.5%, and 5% amino acid PN solutions were stable when combined with midazolam at concentrations of 0.1 and 0.5 mg/mL. PMID- 8480786 TI - Evaluating and selecting an information system, Part 2. AB - Final steps in the evaluation and selection of a computerized information system for the pharmacy department are described. Once the computerization committees have been established, the needs assessment has been conducted, and vendors have responded to the request for proposal, the vendors and their products are subjected to quantitative and qualitative evaluations. The quantitative evaluation involves factors that can be counted, weighted, or tabulated and involves little professional judgment. Vendors can be quantitatively evaluated on the basis of the utility and features of the proposal, the fields to which the product applies, financial strength, product maturity, number of installations, regional presence, user group, software releases and upgrades, personnel, technology, and system costs. The qualitative evaluation requires judgment and intuition and is best performed by pharmacists. Vendors can be qualitatively evaluated on the basis of references, site visits, personnel, demonstrations and presentations, history and plans, user group, product literature, implementation plans, technology, and personalities. The steering committee makes the final selection of a system, and a contract is written that safeguards the hospital's interests. The contract should include performance criteria, promises made orally by salespersons, protection against software and other defects, a phased-in payment schedule, and language covering hardware, support and maintenance, default, and liability. Resources should be budgeted for implementation and stress testing after the contract is signed. Costly errors in selecting a pharmacy information system can be avoided by thoroughly evaluating vendors and writing a contract that protects the hospital. PMID- 8480787 TI - Pharmacy students' experience with identifying and solving drug-related problems during clinical clerkship. PMID- 8480788 TI - Preliminary study of autonomy as a factor influencing medication-taking by elderly patients. PMID- 8480789 TI - Refractometric testing of alfentanil hydrochloride, fentanyl citrate, sufentanil citrate, and midazolam hydrochloride. PMID- 8480790 TI - ASHP guidelines on preventing medication errors in hospitals. PMID- 8480791 TI - Medication error versus medication misadventure--what's in a name? PMID- 8480792 TI - Initial responses to recommendations of the Blue Ribbon Committee on Generic Medicines. PMID- 8480793 TI - Generic and alternative brand-name pharmaceutical equivalents: select with caution. PMID- 8480794 TI - Michael's sign. PMID- 8480795 TI - Where credit is due. PMID- 8480796 TI - Authenticity remembered. PMID- 8480797 TI - Immunization strategy worked. PMID- 8480798 TI - The delivery dilemma: a question of competency. PMID- 8480799 TI - My life as a symptom. PMID- 8480800 TI - Diabetic hypoglycemia: how to keep the threat at bay. PMID- 8480801 TI - Where did the jobs go? PMID- 8480802 TI - IV vesicants: how to avoid extravasation. PMID- 8480803 TI - Moral support for 'Grandparents Who Care'. PMID- 8480804 TI - New relief for esophageal varices. PMID- 8480805 TI - Carpal-tunnel syndrome. PMID- 8480806 TI - Four against infection. PMID- 8480807 TI - Sleuthing on tribal turf. PMID- 8480808 TI - What is transesophageal echocardiography? PMID- 8480809 TI - Selecting a QA glucose meter. PMID- 8480810 TI - 1993 directory of nursing organizations. PMID- 8480811 TI - Neural correlates of mental phenomena. PMID- 8480812 TI - Caring for the AIDS victim: what can we learn? PMID- 8480813 TI - In memoriam George Tarjan, M.D. 1912-1991. PMID- 8480814 TI - Psychosocial impact of HIV-related caregiving on health providers: a review and recommendations for the role of psychiatry. AB - OBJECTIVE: The author considers current knowledge about the stresses of HIV related care and assesses available evidence for the presence of major occupational, physical, and psychiatric morbidity in health care providers involved in intensive HIV-related caregiving. METHOD: The review is based on anecdotal reports of AIDS-care-related psychosocial distress and the literature concerning caregivers' attitudes toward people with HIV illness and HIV-related caregiving, the psychosocial impact of HIV work, and stress related to the ethical and philosophical challenges facing HIV caregivers. RESULTS: Few of the current publications concerning HIV caregiver stress come from the psychiatric literature. Psychiatry appears to lack a strong clinical, educational, research, or policy presence regarding psychosocial stress in HIV care providers. The numerous studies in the nursing, medical, public health, and health education literature do not include any controlled investigations documenting the incidence and prevalence of physical, psychological, occupational, or interpersonal symptoms or disorders in health care professionals who devote a substantial amount of their clinical activities to patients with HIV illness. CONCLUSIONS: Major HIV-related stress in conjunction with other psychiatric morbidity, such as mood disorders, anxiety disorders, substance abuse, and relationship and occupational problems, seems likely in susceptible caregivers. Decisions about the structure and form of delivery of HIV-related care and programs for caregivers must be based on more carefully controlled psychiatric observations of occupational, physical, psychological, and social adaptation to HIV-related work. The author suggests several areas in which psychiatric clinicians, educators, researchers, and policy experts can make major contributions. PMID- 8480815 TI - Neural correlates of self-induced dysphoria. AB - OBJECTIVE: The authors explored the question of whether acute, transient changes in mood are reflected in activation of discrete neuronal systems in the human brain. METHOD: Using positron emission tomography, they measured the regional cerebral blood flow (CBF) of seven psychiatrically healthy subjects under two conditions. During the control condition the subjects were resting with their eyes closed. During the active condition, with their eyes still closed, they were asked to imagine or recall a situation that would make them feel very sad. They were explicitly asked to experience sadness and to avoid any feelings of anger or anxiety. RESULTS: There were significant differences in regional CBF measured during the control condition and during the active condition, particularly in the inferior and orbitofrontal cortices. Women showed bilateral inferior and orbitofrontal activation, but men displayed predominantly left-sided activation in these areas. CONCLUSIONS: The authors conclude that the inferior and orbitofrontal cortices play an important role in normal emotional cognitive processes. PMID- 8480816 TI - The enduring psychosocial consequences of mania and depression. AB - OBJECTIVE: The authors sought to determine the scope, severity, and persistence of psychosocial impairment arising from bipolar and unipolar affective disorder. METHOD: Patients with bipolar (N = 148) or unipolar (N = 240) major affective disorder were assessed as they sought treatment and again after a 5-year follow up. Concurrently, parents, siblings, and adult children underwent similar assessments and were followed for 6 years. To quantify the impact of affective disorder, probands were individually matched to relatives who had no lifetime history of affective disorder. Sixty-nine relatives who were depressed at intake constituted a separate, nonclinical study group and were also matched to relatives who were well. RESULTS: Both unipolar and bipolar patients began follow up with deficits in annual income. Relative to comparison subjects, affective disorder groups were significantly more likely to report declines in job status and income at the end of follow-up and significantly less likely to report improvements. Similarly, both bipolar and unipolar patients showed significant deficits in nearly all other areas of psychosocial functioning measured at follow up. Except for relationships with spouses, deficits did not differ significantly by polarity. Surprisingly, probands with recovery sustained throughout the final 2 years of follow-up also showed severe and widespread impairment. Relatives with major depression exhibited substantial deficits on follow-up, but job status and income were not significantly affected. CONCLUSIONS: The psychosocial impairment associated with mania and major depression extends to essentially all areas of functioning and persists for years, even among individuals who experience sustained resolution of clinical symptoms. PMID- 8480817 TI - Does age make a difference in the effects of physical health and social support on the outcome of a major depressive episode? AB - OBJECTIVE: The authors examined the effects of physical health and social support on 6-month outcome of a major depressive episode in 67 patients who were less than 60 years old and 46 patients who were 60 years old or older. They hypothesized that despite their higher rate of troublesome health problems, older patients would have fewer depressive symptoms at follow-up than would younger patients. METHOD: The Center for Epidemiologic Studies Depression Scale (CES-D Scale) and a modified version of the National Institute of Mental Health Diagnostic Interview Schedule were used to gather data from inpatients and outpatients treated at Duke University Medical Center during a face-to-face interview at baseline and over the telephone at 6-month follow-up. At baseline, all patients met DSM-III-R criteria for a major depressive episode. Data analyses included bivariate and multivariate procedures. RESULTS: At baseline, the mean CES-D Scale scores of the two age groups were similar. As expected, the mean illness index score of the older patients was significantly higher and their mean impaired subjective social support score was slightly lower than those of the younger patients. At 6-month follow-up, the mean CES-D Scale score of the younger patients was above the depressive threshold, but the mean CES-D Scale score of the older patients was below the depressive threshold. The illness index and impaired subjective support measures were significant predictors of depressive symptoms at 6 months for the younger patients but not for the older patients. CONCLUSIONS: The authors conclude that older depressed patients have a more favorable prognosis than younger depressed patients. Predictors of outcome vary by age. PMID- 8480818 TI - Somatization and the recognition of depression and anxiety in primary care. AB - OBJECTIVE: The authors examined the effect of patients' style of clinical presentation on primary care physicians' recognition of depression and anxiety. METHOD: The subjects were 685 patients attending family medicine clinics on self initiated visits. They completed structured interviews assessing presenting complaints, self-report measures of symptoms and hypochondriacal worry, the Diagnostic Interview Schedule (DIS), and the Center for Epidemiologic Studies Depression Scale (CES-D). Physician recognition was determined by notation of any psychiatric condition in the medical chart over the ensuing 12 months. RESULTS: The authors identified three progressively more persistent forms of somatic presentations, labeled "initial," "facultative," and "true" somatization. Of 215 patients with CES-D scores of 16 or higher, 80% made somatized presentations; of 75 patients with DIS-diagnosed major depression or anxiety disorder, 76% made somatic presentations. Among patients with DIS major depression or anxiety disorder, somatization reduced physician recognition from 77%, for psychosocial presenters, to 22%, for true somatizers. The same pattern was found for patients with high CES-D scores. In logistic regression models education, seriousness of concurrent medical illness, hypochondriacal worry, and number of lifetime medically unexplained symptoms each increased the likelihood of recognition, while somatized presentations decreased the rate of recognition. CONCLUSIONS: While physician recognition of psychiatric distress in primary care varied widely with different criteria for recognition, the same pattern of reduction of recognition with increasing level of somatization was found for all criteria. In contrast, hypochondriacal worry and medically unexplained somatic symptoms increased the rate of recognition. PMID- 8480819 TI - Development of aphasia, apraxia, and agnosia and decline in Alzheimer's disease. AB - OBJECTIVE: The purpose of this study was to compare the stage and the subtype models of disease progression in Alzheimer's disease. The authors address the issue of whether the overall rate of clinical decline is different in Alzheimer's disease patients with and without early development of aphasia, apraxia, or agnosia. METHOD: The study was a case series study. Two separate cohorts of Alzheimer's disease patients were used, one from an ongoing single center study at Stanford University (N = 57) and the other from a multicenter project across the state of California (N = 70). Patients were assessed every 6 months in the Stanford study and yearly in the state study. All patients were assessed at least three times. The outcome measure was the average rate of decline on the Mini Mental State examination. RESULTS: The average rates of decline on the Mini Mental State were computed for each subject. Subjects were then divided among groups according to whether and when they exhibited aphasia, agnosia, or apraxia. The effects of the presence of aphasia, agnosia, or apraxia were assessed by comparing the average rates of decline on the Mini-Mental State. CONCLUSIONS: Alzheimer's disease patients who developed aphasia or apraxia declined more rapidly than those patients who did not develop either sign. These results were not attributable to differences in Mini-Mental State scores at entry into the study. The results suggest the presence of subtypes of Alzheimer's disease in which accelerated decline is associated with the early appearance of certain neurological signs. PMID- 8480820 TI - Denial of memory deficit in Alzheimer's disease. AB - OBJECTIVE: Patients with probable Alzheimer's disease often deny or underestimate the severity of their memory impairment. The authors examined the relationships between denial and severity of cognitive impairment and between denial and the presence of depressed mood and sad affect in 128 patients with probable Alzheimer's disease. METHOD: Denial of memory deficit was evaluated by structured interview. Cognition was evaluated with a quantitative examination that assessed performance on 16 subtests. Depression was rated by using a scale that included patients' self-ratings as well as caregivers' and examiners' assessments of the patient's mood and affect. Pearson correlation coefficients were used to quantify the relationship between denial and demographic, cognitive, and depression variables. Stepwise multiple regression analysis was used to further examine the relationship between denial and individual cognitive subset scores. RESULTS: Denial did not correlate with age at onset of Alzheimer's disease, duration of illness, or educational background. It did correlate with gender: women exhibited greater denial than men. A significant correlation was found between denial and overall severity of cognitive deficit and particularly with impairment in object naming. A negative correlation was found between denial and depression. CONCLUSIONS: The association between denial and cognitive impairment may suggest that denial of probable Alzheimer's disease results from disruption of cognitive abilities needed for awareness of illness. The negative association between denial and depression may suggest that depression in Alzheimer's disease is in part reactive in nature. PMID- 8480821 TI - Comorbidity in psychosis at first hospitalization. AB - OBJECTIVE: The authors sought to determine the prevalence and effects of medical and psychiatric comorbidity on initial outcome in a group of patients experiencing a first episode of psychosis. METHOD: Patients with a first episode of psychosis who were consecutively admitted to a hospital (N = 102) were examined for the presence of psychiatric and medical disorders. Patients were given psychiatric diagnoses with the use of the Structured Clinical Interview for DSM-III-R and were rated weekly on symptom rating scales. Outcome variables at discharge were final symptom rating scale scores, length of hospitalization, and recovery on the basis of operationalized criteria. RESULTS: Comorbid diagnoses were present in 52.0% (N = 53) of the patients, and 37.7% (N = 20) had multiple comorbid diagnoses. The most common comorbid diagnosis was substance abuse. Patients with affected psychoses were significantly more likely than those with nonaffective psychoses to have a comorbid substance abuse diagnosis. Patients with psychiatric comorbidity had poorer initial outcomes, while those with medical comorbidity had fewer symptoms at discharge. CONCLUSIONS: Comorbidity is common and may be a useful predictor of the outcome of a first episode of psychosis. PMID- 8480822 TI - Unrecognized cocaine use among schizophrenic patients. AB - OBJECTIVE: Unrecognized stimulant use could lead to the misdiagnosis of schizophrenia or the misunderstanding of its course and prognosis. This study was conducted to determine the prevalence of unrecognized stimulant use among patients with a clinical diagnosis of schizophrenia. METHOD: The subjects were 108 schizophrenic patients admitted consecutively to a Veterans Affairs psychiatric hospital. Admitting psychiatrists supplemented routine clinical evaluations with a semistructured interview regarding recent and lifetime use of alcohol, cocaine, amphetamine, marijuana, and opiates. A urine specimen was assayed for the four illicit drugs. RESULTS: Of the 103 patients who provided a urine specimen, 37 (36%) used cocaine during the 6 months before admission, including 31 who used the drug in the week before admission. Because of the poor reliability of negative self-reports of recent cocaine use, clinicians failed to recognize cocaine use in one-third of the patients with a urine toxicology positive for cocaine metabolites. Two other groups of patients were identified; schizophrenic patients without substance abuse (including alcohol) and schizophrenic patients with substance abuse other than stimulants. Both substance abusing groups were younger than the nonabusing group, but the three groups had similarly high rates of recent psychotic symptoms, homelessness, and unemployment. CONCLUSIONS: Among schizophrenic patients who require hospitalization, clinicians should not rely solely on self-reported stimulant use. Recognition of stimulant use could be improved through routine urine toxicologies for all psychotic patients. The authors suggest that recognition of stimulant use among schizophrenic patients may identify a population with a better prognosis for schizophrenia and different treatment needs. PMID- 8480823 TI - Achieving cocaine abstinence with a behavioral approach. AB - OBJECTIVE: The authors compared the efficacy of a multicomponent behavioral treatment and drug abuse counseling for cocaine-dependent individuals. METHOD: The 38 patients were enrolled in outpatient treatment and were randomly assigned to the two treatments. Counseling in the behavioral treatment was based on the community reinforcement approach, while the drug abuse counseling was based on the disease model of dependence and recovery. Patients in the behavioral, but not the drug counseling, treatment also received incentives contingent on submitting cocaine-free urine specimens. RESULTS: Of the 19 patients who received behavioral treatment, 58% completed 24 weeks of treatment, versus 11% of the patients who received counseling. In the behavioral treatment group 68% and 42% of the patients achieved at least 8 and 16 weeks of documented continuous cocaine abstinence, respectively, versus 11% and 5% in the drug abuse counseling group. CONCLUSIONS: This multicomponent behavioral treatment appears to be an effective intervention for retaining outpatients in treatment and establishing cocaine abstinence. PMID- 8480824 TI - Pharmacotherapy of bulimia nervosa with fluoxetine: assessment of clinically significant attitudinal change. AB - OBJECTIVE: The authors used an individual change model to examine the clinically significant effect of pharmacotherapy with fluoxetine on the attitudes and beliefs characteristic of bulimia nervosa. METHOD: Three hundred eighty-two women meeting DSM-III-R criteria for bulimia nervosa participated in a multicenter, double-blind, randomized clinical trial of placebo, 20 mg of fluoxetine, and 60 mg of fluoxetine for 8 weeks. Behavioral change was assessed with self-monitored measures of binge eating and purging, and psychological change was measured with the self-rating Eating Disorder Inventory and the Hamilton Rating Scale for Depression. A specific statistical method was used to determine clinically significant change in psychological measures. RESULTS: On the majority of psychological measures, more of the subjects receiving active drug than those receiving placebo showed clinically significant change. Behavioral improvement was significantly associated with the likelihood of demonstrating clinically significant psychological change. The observed effect of pharmacotherapy on attitudinal change was not related to the presence of depression at baseline. These results compare favorably with other interventions for bulimia nervosa. CONCLUSIONS: Measures of change in treatment studies should reflect clinical as well as statistical significance. In the short-term, treatment of bulimia nervosa with fluoxetine appears to produce clinically significant attitudinal and behavioral changes. PMID- 8480825 TI - Severity of psychiatric symptoms after HIV testing. AB - OBJECTIVE: The authors were interested in the psychiatric effects of serological testing for HIV and what information feasibly available at intake might predict more severe psychiatric symptoms 1 year later. METHOD: HIV testing in a private office setting was offered to adults at perceived risk for HIV infection but without AIDS. At entry, then 6 and 12 months later, subjects were counseled by psychiatric nurses and assessed by the Hamilton Rating Scale for Depression, Beck Depression Inventory, Spielberger State-Trait Anxiety Inventory, and Brief Symptom Inventory. RESULTS: Mean scores on all measures of psychiatric symptoms were lower at follow-up among both 106 HIV-positive and 222 HIV-negative adults. One year after HIV testing, 121 (37%) of the 328 subjects had scores associated with psychopathology. These elevated scores were not predicted by serostatus but by initial psychopathological scores (N = 150), annual income less than +15,000 (N = 114), being female (N = 46), and history of injection drug use (N = 32) and heterosexual risk factors (N = 60) as compared to males having sex with males (N = 236). CONCLUSIONS: Before the development of more severe physical symptoms, on average, knowledge of HIV infection does not increase psychiatric morbidity; however, regardless of serostatus, a notable percentage of at-risk adults have sustained high levels of psychiatric symptoms. Counseling during the HIV testing process provides an opportunity to identify these individuals for closer study and indicated psychiatric treatment. PMID- 8480826 TI - Clinical course of alcoholism in 636 male inpatients. AB - OBJECTIVE: This study was undertaken to determine the relative order of appearance of symptoms in alcohol dependence. METHOD: The age at which 21 alcohol related major life events first occurred was investigated in 636 male alcohol dependent inpatients through a standardized, structured personal interview with each subject and at least one resource person. RESULTS: A general pattern of first occurrence of these events was observed. Heavy drinking escalated further when the subjects were in their late 20s, followed by evidence of interference with functioning in multiple life areas in the early 30s, a subsequent perception of loss of control, and then an intensification of social and job-related problems, along with evidence of deterioration in body systems, in the mid- to late 30s. Similar patterns of problems emerged when the alcoholic subjects were divided into subgroups based on onset of alcohol dependence before or after age 30, presence or absence of a family history of alcoholism, and presence or absence of additional psychiatric disorders. CONCLUSIONS: These data indicate that there is a typical progression of events related to alcohol dependence. This information can be useful for clinicians in their work with patients and for teachers and researchers as well. PMID- 8480827 TI - Psychiatric disorders in adult children of alcoholics: data from the Epidemiologic Catchment Area project. AB - OBJECTIVE: The authors examined differences in the prevalence of psychiatric disorders in individuals who did or did not have alcoholic parents. METHOD: They used data from the National Institute of Mental Health Epidemiologic Catchment Area project, specifically from the Piedmont of North Carolina. Prevalence of psychiatric disorders was estimated in 408 ECA participants who reported problem drinking in their mother, their father, or both and in 1,477 age- and sex-matched subjects who did not report having alcoholic parents. RESULTS: The adult children of alcoholics showed significantly higher current (6-month) prevalence rates of simple phobia and agoraphobia and lifetime rates of dysthymia, generalized anxiety disorder, panic disorder, simple phobia, and agoraphobia. Adult children of alcoholics also had significantly more antisocial symptoms. Male children of alcoholics had higher rates of alcohol and drug abuse and reported more antisocial symptoms than did female children of alcoholics. Male children of alcoholics had a significantly higher rate of lifetime diagnoses of alcohol and drug abuse than men who were not children of alcoholics. More female children of alcoholics had generalized anxiety disorder than women who were not children of alcoholics. Both male and female children of alcoholics had significantly more antisocial symptoms than their matched comparison subjects. Sons of alcoholic fathers had a higher rate of substance abuse and more antisocial symptoms than did daughters of alcoholic fathers. Daughters of alcoholic fathers had a higher rate of generalized anxiety disorder. CONCLUSIONS: These data on adult children of alcoholics in a large community sample add to a literature based mainly on descriptive material or studies of smaller samples. PMID- 8480828 TI - Missed psychiatric appointments: who returns and who stays away. AB - OBJECTIVE: This study investigated reasons for missed psychiatric appointments, rescheduling of appointments, adverse outcomes, and the association of specific diagnoses and treatments with missed appointments. METHOD: A prospective survey covering all individual outpatient visits to seven mental health clinic psychiatrists was conducted during a 3-month period in 1991. Of the 1,620 scheduled visits, 142 (8.8%) were missed, representing 130 separate patients. For each missed appointment, the psychiatrist involved completed a questionnaire on the type of visit, the patient's DSM-III-R diagnosis, the reason for missing the appointment, the date of patient recontact, and adverse outcome, if any. RESULTS: Of the 142 missed appointments, 71.1% were rescheduled spontaneously by the patients; of these, most (73.3%) were rescheduled within 2 weeks. The remaining missed appointments represented various outcomes, including dropping out of treatment. The most common stated reason for missing an appointment was patient error, such as forgetting, oversleeping, or getting the date wrong. Patients with PTSD and/or substance abuse were significantly more likely than others to miss appointments, and those with major depression were somewhat less likely to do so. CONCLUSIONS: Most patients quickly reschedule missed appointments, and those in more intensive treatments miss fewer appointments. Missed appointments for initial evaluation are not rescheduled most often. Patients in ongoing treatment who do not return may have histories of noncompliance with treatment. The high rate of rescheduling suggests that follow-up of patients who miss appointments should be a clinical decision rather than a routine policy. PMID- 8480829 TI - Ketoconazole administration in hypercortisolemic depression. AB - Ketoconazole, an antiglucocorticoid drug, was administered to 10 hypercortisolemic depressed patients for up to 6 weeks. Three patients dropped out because of side effects or intercurrent illness. The remaining seven had significant ketoconazole-associated decreases in serum cortisol levels and in depression ratings. Antiglucocorticoid agents may be useful probes for investigating the sequelae of hypercortisolemia in patients with major depression. PMID- 8480831 TI - A comparison of treated and untreated simple phobia. AB - The authors compared 25 treated and 58 untreated subjects with simple phobia uncomplicated by other lifetime anxiety disorders. The treated individuals reported more phobias involving dogs and cats, elevators, and transportation; most had multiple phobias; and many experienced panic attacks in the context of their phobias. The untreated individuals typically reported only one phobia, which was often related to blood-injury and was seldom complicated by panic symptoms. PMID- 8480830 TI - CSF transthyretin in patients with depression. AB - Some depressed patients may suffer from restricted central hypothyroidism, which could occur if levels of the thyroid hormone transport protein transthyretin were low. CSF transthyretin was measured in eight inpatients with refractory major depression and nine neurological patients. The depressed patients had significantly lower transthyretin levels than the comparison subjects, suggesting that central hypothyroidism, with normal peripheral thyroid concentrations, could occur in some depressed patients. PMID- 8480832 TI - Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. AB - In a double-blind, crossover study, 13 fluoxetine-treated patients with obsessive compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each. There were no significant differences between buspirone and placebo in obsessive compulsive, depressive, or anxiety symptoms. PMID- 8480833 TI - Buprenorphine versus heroin dependence: comparison of toxicologic and psychopathologic characteristics. AB - Sociodemographic, toxicologic, and psychopathologic characteristics of 22 buprenorphine addicts and 45 heroin addicts admitted for inpatient detoxification were compared. Although the buprenorphine addicts were older, clinically significant differences were not apparent. The availability of buprenorphine may be the main reason for its abuse. PMID- 8480834 TI - Self-induced water intoxication treated with group psychotherapy. AB - The authors conducted a controlled, prospective 4-month study of 10 male inpatients with chronic schizophrenia and polydipsia. The five men who were treated with group psychotherapy drank significantly less fluid than the five men not given this therapy. The effect of group psychotherapy quickly dissipated in the follow-up period, indicating the need for ongoing treatment. PMID- 8480835 TI - Development of obsessive-compulsive symptoms during clozapine treatment. PMID- 8480836 TI - Interaction between fluoxetine and neuroleptics. PMID- 8480837 TI - Detectable levels of fluoxetine metabolites after discontinuation: an unexpected serotonin syndrome. PMID- 8480838 TI - Precipitation of dystonia by m-CPP in a schizophrenic patient treated with haloperidol. PMID- 8480839 TI - HLA and panic disorder. PMID- 8480840 TI - Ultrashort noninvasive opiate detoxification. PMID- 8480842 TI - Treatment with drugs and drug testing. PMID- 8480841 TI - Allegations of abuse in psychotic patients. PMID- 8480843 TI - Multiple personality disorder in Europe. PMID- 8480844 TI - Panic as a posttraumatic stressor. PMID- 8480845 TI - Panic as a posttraumatic stressor. PMID- 8480846 TI - CPM in polydipsic psychiatric patients. PMID- 8480847 TI - Serotonin and Parkinson's disease. PMID- 8480848 TI - Buspirone, anxiety, and sleep. PMID- 8480849 TI - Differences in late- and early-onset schizophrenia. PMID- 8480850 TI - Psychotherapy and borderline personality disorder. PMID- 8480851 TI - Women in academic psychiatry and research. PMID- 8480852 TI - AIDS policy: position statement on confidentiality, disclosure, and protection of others. Commission on AIDS. PMID- 8480853 TI - AIDS policy: guidelines for inpatient psychiatric units. Commission on AIDS. PMID- 8480854 TI - Hemoglobin catabolism and host-parasite heme balance in chloroquine-sensitive and chloroquine-resistant Plasmodium berghei infections. AB - Catabolism of host hemoglobin by the malaria parasite liberates required amino acid precursors, but is also releases large amounts of potentially toxic heme that accumulates in parasite food vacuoles during intra-erythrocytic development. The schizonticidal drug chloroquine binds to free heme with high affinity and is concentrated in parasite food vacuoles. To better understand the disposition of heme within the host-parasite complex, we studied the balance of hemoglobin and heme in Plasmodium berghei-infected reticulocytes in the rat and compared this process in chloroquine-sensitive (CS) and chloroquine-resistant (CR) parasites. We found that CS P. berghei parasites have 1.5-fold more heme than CR parasites isolated from rats, and that CS P. berghei-infected reticulocytes accumulate more chloroquine than CR P. berghei-infected reticulocytes. Despite these differences in parasite heme content, the decrease in host cell hemoglobin content and the rate of free amino acid generation within the host-parasite complex is similar in CS and CR P. berghei-infected rat reticulocytes. The heme content of the infected reticulocyte-parasite complex decreases with increasing parasitemia but to a lesser extent than expected for the decrease in hemoglobin. Furthermore, the decrease in host-parasite heme is accelerated in the CR P. berghei infection compared with the CS P. berghei infection. Therefore, hemoglobin catabolism by malaria parasites is associated with the overall loss of heme from the host parasite complex and with variable deposition of heme within parasites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480855 TI - Oxidative stress and Trichomonas vaginalis: the effect of hydrogen peroxide in vitro. AB - The oxidative stress response induced in Trichomonas vaginalis by exposure to various concentrations of hydrogen peroxide (H2O2) was traced by metabolic labeling and monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography of trichloroacetic acid-precipitated proteins. Concentrations of H2O2 > 450 microM decreased incorporation of radiolabel into protein and altered protein synthesis resulted in a banding pattern similar to the heat shock protein profile. The proteins produced by oxidative stress included molecules with average molecular masses of 145-165, 92-84, 66, 43-46, and 35-36 kD. Oxidative stress induced changes in T. vaginalis protein synthesis slowly. Full conversion to oxidative stress response occurred within 150-180 min after stress initiation. The oxidative stress responses of three strains freshly initiated from stabilates were compared with the responses of the same strains cultured in vitro for extended periods (culture adapted). Both freshly initiated and culture adapted T. vaginalis of the three strains synthesized the 92-84- and 66-kD heat shock proteins but differed in the synthesis of the 74-75-, 43-, and 35-36-kD molecules. Culture adaptation did not modify the oxidative stress response of the three strains tested. PMID- 8480856 TI - Induction of adhesiveness in human endothelial cells by Plasmodium falciparum infected erythrocytes. AB - Cytoadhesion of infected erythrocytes to endothelium plays an important role in the pathogenesis of Plasmodium falciparum malaria. In vitro assays of cytoadhesion have helped to identify putative host ligands, namely thrombospondin, platelet glycoprotein IV (CD36), and intercellular adhesion molecule-1 (CD54) as possible mediators of cytoadhesion. However, the presence of these ligands on some host cells to which infected erythrocytes do not adhere raises the possibility that other molecules or factors may be involved. In the present study, we investigated the effects of prolonged incubation of endothelial cells (EC) with infected erythrocytes on adhesiveness of EC. We also studied the effects of tumor necrosis factor (TNF), interleukin-1 (IL-1), and phorbol myristate acetate (PMA). We found that when EC were incubated in contact with ring-infected erythrocytes for 24 hr during which the rings developed into trophozoites, adhesiveness was enhanced up to 250%. Incubation of EC with IL-1 or TNF for 12 hr increased adhesiveness by 50% at minimum doses of 5 U/ml and 50 U/ml, respectively, while PMA decreased adhesiveness in a consistent and dose dependent manner. These results show that host EC adhesive ligands for infected erythrocytes can be induced, most notably by direct contact between the EC and infected erythrocytes containing developing parasites. The cultured human EC used in this study lacked surface CD36 detectable by immunofluorescence assay, suggesting that CD36 is not required for endothelial adhesiveness. PMID- 8480857 TI - Biology and pathology of Schistosoma mansoni and Schistosoma japonicum infections in several strains of nude mice. AB - Schistosoma mansoni and S. japonicum infections in nude mice (nu/nu) were compared with infections in nu/+ heterozygotes or intact mice. Seven to 12 weeks after exposure to S. mansoni, the responses of Swiss NCR, C3H, BALB/c and C57B1/6 nude mice did not differ substantially. Nude mice of all these strains showed minute granulomas around eggs in the liver and minimal hepatic fibrosis. Microvesicular and necrotizing changes in hepatocytes were similar in all mouse strains, and S. mansoni infections were frequently lethal to nude, but not to intact mice between the seventh and ninth weeks of infection. Nude mice that survived the ninth week of infection generally lived until the 12th week. The number of eggs per mature worm pair in the tissues of S. mansoni-infected nude mice was similar to the number in intact mice, but nude mice passed fewer eggs in the feces. Nude mice that received serum from infected intact mice excreted eggs in the stool in numbers equivalent to intact mice, but continued to form minute granulomas around S. mansoni eggs. Reconstitution with fetal thymus or with splenocytes from normal or S. mansoni-infected mice partially or completely restored hepatic granuloma size, granuloma eosinophils, hepatic fibrosis, and excretion of eggs in the feces. In contrast to S. mansoni infection, S. japonicum infections in nude mice did not cause necrosis of hepatocytes or excessive mortality, and S. japonicum eggs were passed in the feces in numbers equivalent to those passed by infected intact mice. PMID- 8480858 TI - Differential sequestration of parasitized erythrocytes in the cerebrum and cerebellum in human cerebral malaria. AB - Sequestration of parasitized red blood cells (PRBC) in the microvessels results in impairment of microcirculation with organ dysfunction in complicated human Plasmodium falciparum malaria. In cerebral malaria patients, the percentage of small blood vessels with PRBC sequestration is higher in the brain than in other organs. The clinical severity of cerebral malaria depends on the level of PRBC sequestration in the brain. In our study, postmortem samples from cerebrum and cerebellum of 16 patients who died of P. falciparum malaria were examined and compared using light microscopy. In the cerebellum, the percentage of microvessels with PRBC sequestration was higher than that in the cerebrum. The difference in sequestration rates between cerebrum and cerebellum is statistically significant (P < 0.05). There is a higher degree of vascularity in the cerebellum (7 vessels/mm2) than in the cerebrum (5 vessels/mm2), and the difference is also statistically significant (P < 0.025). Perivascular hemorrhages also occur more frequently in the cerebellum than in the cerebrum. The results of this study, which show that differential sequestration of PRBC occurs in the microvessels of the cerebrum and cerebellum, explain the varied neurologic manifestations that result from cerebral and cerebellar dysfunction in human cerebral malaria. This study also reveals the necessity of postmortem histologic examination of the cerebellum in every suspected case of cerebral malaria. PMID- 8480859 TI - Development of in vitro parameters of cell-mediated immunity in the course of human cutaneous leishmaniasis infection. AB - The goal of the present study was to determine whether a correlation between the clinical stage of cutaneous leishmaniasis lesions and in vitro parameters of cell mediated immunity could be established. For this purpose, we measured lymphocyte proliferation, using a total lymphocyte proliferation (TLP) blood assay, and leishmanicidal effector activity using peripheral blood mononuclear cells (PBMC) in a three-day assay. The parameters of leishmanicidal activity measured included percent infected monocytes and number of amastigotes per 100 infected monocytes 24 and 72 hr after infection. Three groups of people were studied: a group of patients in the course of the disease, a group of immune individuals, and unexposed controls. The results of the study suggested that the ability of PBMC to kill parasites increased in patients as the lesions cured, and was highest in immune individuals. In contrast, the TLP response once positive, did not increase after cure. In approximately 30% of the patients who were retested on several occasions during the course of the disease, a positive response reversed to negative both in the TLP and the effector assays while the lesions were still active. In approximately 50% of these cases, the response eventually became positive again. The data presented show that effector activity and proliferation correlate with immunity, and suggest that marked heterogeneity characterizes the immune response in the course of active disease. PMID- 8480860 TI - Enhancement of resistance to Cryptosporidium parvum by pooled bovine colostrum during murine retroviral infection. AB - The therapeutic efficacy of pooled bovine colostrum for the control of cryptosporidiosis was investigated during murine acquired immunodeficiency syndrome in female C57Bl/6 mice. Mice were infected with LP-BM5 murine leukemia retrovirus for four months and then inoculated with Cryptosporidium parvum oocysts. Persistent cryptosporidiosis was established in all retrovirus immunosuppressed mice, while control mice were refractory to infection. Parasite colonization of intestinal villi was significantly (P < 0.05) reduced in immunosuppressed animals that received dietary supplemental pooled bovine colostrum compared with to those that did not receive colostrum treatment. Similarly, shedding of oocysts in the feces of immunosuppressed animals that received dietary pooled bovine colostrum was significantly (P < 0.05) reduced compared with those that did not at 26 days post-parasite challenge. Since the nonimmune bovine colostrum contained no anti-Cryptosporidium antibodies, this suggests that passively transferred antibodies alone are unlikely to have provided the improved resistance shown in this study. PMID- 8480861 TI - Leishmania donovani parasites in the nasal secretions, tonsillopharyngeal mucosa, and urine centrifugates of visceral leishmaniasis patients in Kenya. AB - In the early 1930s, investigators of visceral leishmaniasis stated that Leishman Donovan bodies are found in body fluids of kala-azar patients, for example, in urine, feces, semen, and nasal and pharyngeal secretions. Based on this finding, we investigated the diagnostic potential of nasal secretions, tonsillopharyngeal mucosal swabs, and urine centrifugates inoculated into Schneider's Drosophila Medium (containing antibiotics and antifungal agents) as well as with Giemsa stained smears. Consequently, 64 randomly selected patients with visceral leishmaniasis from Kenya (59 who were splenic culture or Giemsa stain positive and five who were culture negative but Giemsa stain positive) were tested by three noninvasive methods. These tests were all performed before the patients were treated with Pentostam. Cultures of nasal and tonsillopharyngeal swabs and urine centrifugates produced 28 positive samples representing 24 patients (37.5%). Moreover, a set of 25 Giemsa-stained slide smears made from the nasal and tonsillopharyngeal mucosa of 25 patients with visceral leishmaniasis who had not tested positive in cultures produced nine positives. Therefore, the overall total of patients who tested positive by all of the above methods was 33 or 51.6%. The cryopreserved Leishmania isolates were characterized by cellulose acetate electrophoresis using 20 enzyme systems. The isoenzyme profiles produced by the parasites were represented in five different L. donovani s.l. zymodemes. Representatives of these isolates were also characterized by DNA Southern blotting analysis, which corroborated the isoenzyme results. PMID- 8480862 TI - Immunodiagnosis of human dirofilariasis in Puerto Rico. AB - A seroepidemiologic study was carried out in humans inhabiting southeastern Puerto Rico, the area on this island with highest prevalence of canine heartworm, to detect the presence of antibodies to Dirofilaria immitis. Three hundred serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) using somatic antigens of the adult worm. Serum samples from eight patients were positive for anti-dirofilarial IgG. These patients had a mean age of 54 years. Although the study population had a female: male of 2.5:1, six out of the eight positive sera were from males. The minimum prevalence of human dirofilariasis was conservatively estimated to be 2.66%. After Western blot analysis of positive sera, four polypeptide markers with M(r) values of 15, 33, 42, and 69 kD were selected as potential immunologic markers for this human infection. Three of them (15, 33, and 69 kD) were specifically reactive only with ELISA-positive sera. The 42-kD polypeptide reacted strongly with ELISA-positive sera, although it reacted weakly with some of the ELISA-negative controls. The 15-, 33-, and 69-kD polypeptides were recognized by positive sera in several combinations, but only those sera with the highest ELISA optical density values reacted with all three polypeptides. PMID- 8480863 TI - A case of intestinal capillariasis in the Republic of Korea. AB - In 1991, we observed a Korean man infected by Capillaria philippinensis who had no history of traveling in known endemic areas. He had year-long diarrhea with severe loss of body weight. He enjoyed hunting and fishing and eating raw meat of game animals and fish. An open full-thickness biopsy of the ileum showed flat mucosal surface and sections of the round worm, and fecal examination revealed numerous elliptical helminth eggs. The worms and eggs were consistent with features of C. philippinensis. He was treated with albendazole and was cured. This is the first known case of intestinal capillariasis in the Republic of Korea. PMID- 8480864 TI - Child growth, nutritional status, and schistosomiasis japonica in Jiangxi, People's Republic of China. AB - The association between schistosomiasis japonica and nutritional status and child growth was studied cross-sectionally in 239 males and females (age range 4-19.9 years) residing in Jishan Island in Po Yang Lake in an endemic region of Jiangxi, China. The presence of Schistosoma japonicum eggs in Kato stool smears and the intensity of schistosomiasis as assessed by quantitative egg count were determined, as were the presence of hookworm, Ascaris, and Trichuris eggs. Anthropometric measures included stature, weight, weight-for-height, upper arm muscle area, and the sum of triceps and subscapular skinfold thickness. The association between schistosomiasis and nutritional status and growth was analyzed with multivariable models adjusted for the influence of age, age2, and polyparasitism. The prevalence of schistosomiasis was approximately 70% in both males and females. Current schistosomiasis and its intensity were significantly related to reduced stature, weight, weight-for-height, and the sum of skinfolds (all P < 0.01) in females across the entire age-span. The greatest age-specific differences were during adolescence in females: 4 cm in height and 5 kg in weight. In males, intensity of schistosomiasis was related (P < 0.03) only to the sum of skinfolds. The cross-sectional associations between anthropometric reductions and schistosomiasis japonica in childhood and adolescence indicate a strong independent effect of infection on malnutrition and growth in this population from a highly endemic region of China. PMID- 8480865 TI - Etiology of hypoferremia in a recently sedentary Kalahari village. AB - To determine the etiology of hypoferremia in recently sedentary hunter-gatherers, a community located in the Kalahari Desert of Botswana was studied. Iron profiles of 106 Basarwa (Bushmen, San) volunteers were examined. Hematocrits were measured in the field. The remaining blood was processed for transportation to a research medical laboratory for further studies. Subnormal serum iron values were present, depending on the subpopulation, in 50-52% of the volunteers. Transferrin saturation was subnormal in 35-49% of those tested. The absence of subnormal serum ferritin levels indicates that dietary iron deficiency is not the cause of the hypoferremia. Instead, serum ferritin was greater than 50 micrograms/l (a level indicative of anemia of chronic disease/inflammation) in 92% of the hypoferremic adult Basarwa. We suggest that by depriving microbes of needed iron, the frequency of the anemia of infections and chronic disease in this population might be a response to, and defense against, a chronically high pathogen load in a community that has not yet incorporated sanitation practices appropriate for sedentary aggregations. PMID- 8480866 TI - Comparison of human trichinellosis caused by Trichinella spiralis and by Trichinella britovi. AB - The first documented report of an outbreak of human trichinellosis caused by Trichinella spiralis in Italy is described. Two family groups were involved. The source was wild boar meat products. The principal clinical features were fever (60%), myalgia (50%), and diarrhea (40%). The most useful laboratory indicators were eosinophilia (100%), elevated levels of creatine phosphokinase (CPK) (90%) and other muscle enzymes, parasite-specific IgG titers (100%), and anti-newborn larvae antibodies (30%). The levels of these responses correlated with the number of infective muscle larvae ingested, which was influenced by the length of time the ingested meat was cured. The clinical and biological features observed during human infection with T. spiralis appear to have been different from those reported during two outbreaks due to T. britovi, which occurred in southern Italy. The main distinctions between the two types of infections were a longer duration of parasite-specific IgG, increased CPK levels, and a more severe intestinal symptomatology in T. spiralis-infected patients than in those infected with T. britovi. PMID- 8480867 TI - Transmission of Crimean-Congo hemorrhagic fever virus in two species of Hyalomma ticks from infected adults to cofeeding immature forms. AB - Crimean-Congo hemorrhagic fever (CCHF) virus was transmitted from infected adult Hyalomma ticks to uninfected larval and nymphal Hyalomma ticks while cofeeding on a guinea pig host that did not have a detectable viremia. When tested after feeding with infected adults, three (0.8%) of 370 H. truncatum larvae contained detectable CCHF virus (mean virus titer 10(1.6) plaque-forming units [PFU]/tick). The virus was transmitted transstadially from infected larvae and was detected in 15 (1.2%) of 1,253 nymphs and 12 (0.1%) of 2,049 adults. Virus was recovered from 18 (1.9%) of 931 H. impeltatum nymphs, which originated from larvae that cofed with infected adults. After H. impeltatum nymphs cofed with infected adults, CCHF virus was detected in 21 (4.3%) of 449 (mean virus titer 10(1.7) PFU/tick) fed nymphs, but none of 886 adults tested after molt. Results of this study indicate that a small proportion of either larvae or nymphs may acquire CCHF infection while cofeeding on a host without a detectable viremia. PMID- 8480868 TI - Treatment of subperiodic Brugia malayi infection with a single dose of ivermectin. AB - A clinical trial on the efficacy of a single oral dose of ivermectin at 20, 50, 100, and 200 micrograms/kg was carried out in 40 subjects with subperiodic Brugia malayi microfilaremia. There was no significant difference in the clearance of microfilaremia in the four treatment groups, and the lowest geometric mean microfilarial count (GMC) achieved in the 40 subjects was 8.8/ml or 8.3% of the initial count (106.1/ml), at two weeks post-treatment. The GMC started to increase at one month post-treatment and by six months was 22.2% of the initial GMC. Only 27.5%, 23.1%, 15.0%, and 18.9% of subjects were amicrofilaremic at two, four, 12, and 24 weeks post-treatment, respectively. Mild fever in 35% of the subjects was the primary side reaction and was more common in those with microfilarial counts > or = 500/ml (85.7%) than in those with counts < 500/ml (32%). The clearance of B. malayi microfilaremia by ivermectin was less rapid than that reported for Wuchereria bancrofti. The smaller number of side reactions encountered in the present study compared with those reported for bancroftian filariasis is probably related to the lower microfilarial density in the present subjects. Since ivermectin at a single oral dose of 20-200 micrograms/kg can reduce the GMC to less than 10% at two weeks and maintain it below 25% of the initial level even at six months post-treatment, it is recommended that the drug be seriously evaluated for use in the control of brugian filariasis. PMID- 8480869 TI - Proceedings of the NIH Consensus Development Conference on Gallstones and Laparoscopic Cholecystectomy. Bethesda, Maryland, September 14-16, 1992. PMID- 8480870 TI - National Institutes of Health Consensus Development Conference Statement on Gallstones and Laparoscopic Cholecystectomy. PMID- 8480871 TI - Natural history of asymptomatic and symptomatic gallstones. AB - Review of the sparse literature on the prognosis of asymptomatic and mildly symptomatic gallstones reveals a diversity of methods, definitions, and groups of patients studied, which makes it difficult to draw conclusions. It appears that serious symptoms and complications develop in about 1% to 2% of patients with asymptomatic gallstones annually, with fewer complications developing in later years than in years soon after gallstones are discovered. In patients with stones with mild symptoms, rates of the development of complications are perhaps a little higher, about 1% to 3% per year. In patients who are initially mildly symptomatic, cholecystectomy for severe symptoms probably is undertaken in 6% to 8% per year in the early years, decreasing with longer follow-up. Other than symptoms, no factors related to prognosis have been established. Acute cholecystitis is the most common severe complication of gallstones. Based on follow-up studies, obstructive jaundice, cholangitis, pancreatitis, and cancer of the gallbladder are infrequent complications. Risk of subsequent colon cancer should not ordinarily be a factor when cholecystectomy is considered. Analyses of cost-effectiveness have not demonstrated substantial differences in life expectancy between patients with asymptomatic gallstones who undergo immediate open cholecystectomy compared with watchful waiting. PMID- 8480872 TI - Clinical manifestations and impact of gallstone disease. AB - The main symptom of gallstone disease is biliary pain. Biliary pain is not necessarily colicky or postprandial, and it most frequently occurs at night during the same clock-time. The relief of biliary pain by cholecystectomy would support the idea that the gallbladder or the stones caused pain. Long-term follow up studies after cholecystectomy are infrequent, however. Our studies show that biliary pain is relieved in 99% of patients after 4 years of follow-up. The nonspecific symptoms associated with gallstones (i.e., dyspepsia, bloating, belching, etc.) remained in 12% of these patients. We have also shown that the gallbladder itself, without stones, can cause pain and that this biliary pain is relieved in 77% of patients by cholecystectomy. The impact of gallstones on the patient depends on the quality of cholecystectomy as classically measured by morbidity and mortality. However, quality must also be monitored by comparing the long-term relief of biliary pain and the cost. Quality cannot be monitored through inaccurate national databases or multicenter trials. Rather, the continuous quality improvement (CQI) technique of larger centralized health care systems may be the most accurate monitoring system. This technique coordinates the entire health care system by assuming that any process can improve its quality, no matter how good it may already be. Our CQI laparoscopic cholecystectomy database has yielded preliminary perspectives on accurate data collection and improving costs. After a thorough examination, 5% of the database contained cases not done laparoscopically (coding errors), whereas it missed 21% of true laparoscopic cholecystectomy cases (staff errors). Only with the accuratized database were we able to provide insight into cost-savings procedures. PMID- 8480873 TI - Pathogenesis of gallstones. AB - Gallstones form as a result of many disorders. Unphysiologic supersaturation, generally from hypersecretion of cholesterol, is essential for the formation of cholesterol gallstones. The other common abnormalities of the hepatobiliary system in gallstone patients are accelerated nucleation, gallbladder hypomotility, and the accumulation of mucin gel. An attempt is made here to relate hypersecretion of cholesterol and biliary supersaturation to the molecular basis of the associated phenomena. Supersaturation of bile with calcium hydrogen bilirubinate, the acid calcium salt of unconjugated bilirubin, is essential for pigment gallstone formation, but its magnitude remains undefined in model systems. Nucleation and the precipitation of calcium hydrogen bilirubinate with the polymerization of the pigment in the gallbladder, together with the deposition of the inorganic salts, calcium carbonate and phosphate, result in black pigment gallstone formation. On the basis of ex vivo muscle studies, gallbladder hypomotility is unlikely in patients with black pigment stones but is invariably present in patients with cholesterol stones. Pigment supersaturation in the gallbladder is the result of hepatic hypersecretion of bilirubin conjugates in hemolytic disorders and possibly enterohepatic cycling of unconjugated bilirubin in nonhemolytic states. Less common is bile salt hyposecretion from impaired synthesis in constitutional disorders and cirrhosis, and uncompensated interruption of the enterohepatic circulation in ileal dysfunction syndromes. Bile salt deficiency causes incomplete solubilization of unconjugated bilirubin and impaired binding of calcium ions. Stasis and anaerobic bacterial infection are responsible for brown pigment stones, which usually form in the bile ducts. In addition to the precipitation of calcium hydrogen bilirubinate that remains unpolymerized, there is also the deposition of the calcium salts of saturated fatty acids and free bile acids, both of which are the result of bacterial enzymatic hydrolysis of biliary lipids. PMID- 8480874 TI - Overview of therapeutic modalities for the treatment of gallstone diseases. AB - The management of gallstone diseases has been revolutionized in less than 2 years by the advent of laparoscopic cholecystectomy (LC). However, the rapid adoption of LC has occurred without comparative randomized trials with other available therapies. Thus, the evaluation of LC versus other therapies can only be based on case series. The criteria used for this evaluation are clinical effectiveness, cost-effectiveness, and the patient's level of acceptance and satisfaction with the procedure. The techniques of both LC and open cholecystectomy (OC) have the advantage over other approaches, such as extracorporeal shock-wave lithotripsy or bile acid therapy, of eliminating not only the gallstones but also the gallbladder, thereby preventing recurrence of the disease. Additionally, medical therapies are effective in only a subgroup of patients. Since the complications of surgery are more frequent and more severe in older patients and, due to life expectancy, the risk of recurrence is lower in this population, cost effectiveness analyses have shown that medical therapies may be preferable in older patients in the subgroup eligible for the respective medical therapies. Compared with OC, LC results in a reduction in hospital stay and time to return to work, in lower cost, and in higher patient satisfaction with the procedure. However, a major concern with the laparoscopic approach has been an increase in the incidence of bile duct injury, particularly during the learning phase of the procedure. Clearly, this problem must be solved. The development of training courses in laparoscopy and the adoption of rigorous criteria for ductal identification are critical in preventing such injuries. Bile duct injury can probably be reduced at least to the level of OC (about 1 in 1,000). Acute cholecystitis may also be treated by LC, but the safety and timing of surgery should be conclusively evaluated. Patients with gallbladder stones and choledocholithiasis are usually treated by endoscopic sphincterotomy either before or soon after laparoscopic surgery. Laparoscopic techniques of common bile duct exploration that will obviate the need for endoscopic sphincterotomy are in the developmental stages. When such a technique is available, comparative trials with endoscopic sphincterotomy will be necessary to assess the best approach. PMID- 8480875 TI - Oral and contact dissolution of gallstones. AB - The appropriate selection of patients for treatment with oral ursodeoxycholic acid (UDCA)--a drug that has virtually no side effects--results in about 50% of patients experiencing safe dissolution of gallstones within 2 years. Eligible patients have small (less than 20 mm in diameter) radiolucent gallstones in a gallbladder visualized by oral cholecystography (OCG); ideal candidates are thin women who have gallstones that are less than 15 mm in diameter, floating when observed by OCG, or of low density on computed tomographic (CT) scanning. Contact dissolution with methyl tert-butyl ether (MTBE) is rapid, effective more often than UDCA, and safe but requires the expertise of an interventional radiologist. Any size and number of cholesterol gallstones that are not CT-dense will be dissolved by MTBE, leaving at most only insoluble debris that is clinically innocuous. Although gallstones recur after dissolution by UDCA or MTBE in 50% of patients within 5 years, recurrent gallstones are usually asymptomatic and/or can probably be dissolved. We conclude that oral or contact dissolution provides an alternative treatment to cholecystectomy for about 30% of patients with symptomatic gallstones. PMID- 8480876 TI - Gallstone lithotripsy. AB - Extracorporeal shock-wave lithotripsy (ESWL) has been applied to patients with gallstones since the mid-1980s. Lithotriptors differ by their means of shock-wave generation, the mechanisms by which they are coupled to the patient, and their imaging systems. Entry in most treatment protocols is limited to symptomatic patients with one to three radiolucent stones having a diameter of 30 mm or less and a functioning gallbladder according to oral cholecystography. Treatments are given on an out-patient basis using intravenous analgesia and include adjuvant bile acid therapy. Deaths have not been reported, and the incidence of serious complications, related to the presence of fragments in the biliary system, is low. The studies show that ESWL is a safe and effective treatment for patients with a single gallstone less than or equal to 20 mm in diameter, but the efficacy for larger single stones and multiple stones is poor. To date, the Food and Drug Administration has not approved lithotriptors for the treatment of gallstones in the United States. PMID- 8480877 TI - Open cholecystectomy. AB - The experience with "open" biliary tract surgery is documented in this report in an effort to provide a basis for comparison with the more recent experience with laparoscopic cholecystectomy. During the years 1932 through 1984, 14,232 patients were surgically treated for nonmalignant biliary tract disease at The New York Hospital-Cornell Medical Center. Among these patients, the mortality rate was 1.7% (237 postoperative deaths). Cholecystectomy was performed in 10,749 patients, and the mortality rate was 0.6% (60 postoperative deaths). Of this group of patients, chronic cholecystitis was present in 8,910 patients, and the mortality rate was 0.4% (38 postoperative deaths). Acute cholecystitis was present in 1,839 patients, and the mortality rate was 1.2% (22 postoperative deaths). Choledochotomy as a component of the primary biliary tract operation was performed in 2,226 patients (15.6%), and there were 89 postoperative deaths (4%). In the last 6 years of this study (1978 through 1984), 1,693 patients underwent cholecystectomy alone, and the mortality rate was 0.2% (3 postoperative deaths). PMID- 8480878 TI - Mini-lap cholecystectomy. AB - With the introduction of laparoscopic cholecystectomy, the surgical community witnessed a revolution in basic ideology. Gone are the days when surgeons spoke of wounds healing "from side to side, and not top to bottom." The surgical community has become aware of the concept of minimally invasive surgery. Despite this recent advance, surgeons have long realized that the surgical wound does contribute to morbidity and mortality. The mini-lap cholecystectomy, described as early as 1982, is an indication that surgeons are making an attempt to reduce this morbidity. Mini-lap cholecystectomy is now being suggested as an alternative to laparoscopic cholecystectomy--a technique that boasts many of the same benefits without the problems inherent in laparoscopic surgery. The author has reviewed the literature for mini-lap cholecystectomy, laparoscopic cholecystectomy, and conventional cholecystectomy. Using this "historical" database, he then compares the three techniques to determine whether mini-lap cholecystectomy is a viable alternative. PMID- 8480879 TI - Laparoscopic cholecystectomy: the European experience. AB - Laparoscopic cholecystectomy, initially performed in France in 1987, has rapidly spread to other European countries, the United States, and elsewhere. Of the techniques that have evolved, the "French" technique, in which the surgeon stands between the patient's legs, and the "American" technique, in which the surgeon stands on the patient's left side, are the most commonly used. In the former technique, the liver is retracted via the mid-clavicular cannula and the infundibulum of the gallbladder via the anterior axillary port. In the latter technique, the liver is retracted by axial traction on the gallbladder through the anterior axillary cannula and the infundibulum through the mid-clavicular cannula. This position may increase the risk of bile duct injury. The technique selected for operative cholangiography should be adapted to the problem at hand. Cystic duct cholangiography shows ductal calculi more reliably due to better filling of the common bile duct; direct puncture of the gallbladder is safer when the biliary anatomy is unclear. A number of European studies confirm the safety of laparoscopic cholecystectomy. Mortality rates vary between 0% and 0.1%, and duct injury rates range between 0.2% and 0.6%. Conversion, which is done in 3% to 8% of cases, may be necessary in the case of uncontrollable hemorrhage, bile duct injury unsuitable for laparoscopic repair, or if the gallbladder is densely scarred (scleroatrophic). It can also be done for safety reasons, when the anatomy is unclear. Complications include bile collections due to accessory duct or cystic duct stump leaks or less commonly to common duct injury. The average postoperative stay is longer in Europe (3.2 days) than in the United States. A decision tree is presented for the management of common bile duct stones. In general, preoperatively identified ductal stones are removed by endoscopic sphincterotomy, which is then followed by laparoscopic cholecystectomy to remove the source of the calculi. The techniques of laparoscopic choledochotomy and transcystic exploration for the removal of stones in the common bile duct are only beginning to be used, but they may well prove to be the most popular procedures. Results with these procedures will need to be evaluated against those obtained with endoscopic sphincterotomy. PMID- 8480880 TI - U.S. experience with laparoscopic cholecystectomy. AB - Thirteen published series concerning laparoscopic cholecystectomy performed in the United States were reviewed. The review was based on reports that included at least 100 patients. Three of the series are surveys of surgery chairpersons and multiple hospitals. The other 10 series are based on the experience of the investigators. The operation was performed by trained and qualified surgeons, usually in females with early gallbladder and gallstone disease. The patient profiles were similar, and the outcomes were favorable. The incidence of complications and deaths was very low, but the rate of injury to the common bile duct was slightly higher in laparoscopic cholecystectomy than in open cholecystectomy. Intraoperative cholangiography can be performed selectively. The major benefits to the patient are a short hospital stay, early return to activity, and a reduced hospital bill. PMID- 8480881 TI - Laparoscopic versus open cholecystectomy: the Canadian experience. The McGill Gallstone Treatment Group. AB - Numerous uncontrolled trials have suggested that laparoscopic cholecystectomy (LC) is a major improvement over open cholecystectomy (OC). In an effort to objectively document the benefits of LC, two Canadian studies are reviewed. The first is a matched time series based on prospective data from a single surgeon's practice in which patients are closely matched for baseline characteristics. The groups consist of 121 patients from each of 3 time periods: 1989, prior to the introduction of LC; 1990, when LC was being introduced; and 1991, when LC had become the preferred method of cholecystectomy. The second study is a randomized trial, in which LC is compared with mini-cholecystectomy. In both studies, the superior efficacy of LC is demonstrated with respect to the duration of hospitalization and the duration of postoperative convalescence. The incidence of complications as well as their severity is also less in LC patients. Although quality of life improves after any type of cholecystectomy, LC patients improve faster and seem to accept the operation better. These studies support the widespread dispersion of LC in Canada, although comparative efficacy with nonsurgical alternatives has not been addressed. PMID- 8480882 TI - Comparison of laparoscopic cholecystectomy with open cholecystectomy in a single center. AB - In this retrospective study, we compared the results of 1,283 open cholecystectomies (OCs) performed at our medical center during the pre laparoscopic era with 1,107 laparoscopic cholecystectomies (LCs) performed from 1990 to 1992. There was no difference in the percentage of cases of acute and chronic cholecystitis in each time period (16.8% in each), nor were there differences in the patient characteristics for each group. The percentage of patients undergoing intraoperative cholangiography was similar for patients with chronic cholecystitis for each period, although the incidence of abnormal cholangiograms was lower in the laparoscopic era (5.8% versus 15.2%, p < 0.001). There was one bile duct injury in the OC group and three in the LC group (although one of these occurred after conversion ot an open procedure), but this difference was not statistically significant. However, there was a higher mortality rate in the patients with acute cholecystitis treated with OC (2.3% versus 0%, p = 0.03) and an increase in the overall complications in the patients with chronic cholecystitis in the OC group (7.5% versus 3.1%, p < 0.001) compared with the LC group. The increase in overall complications appeared to be primarily related to the increased rate of wound-related complications (3.6% versus 0%, p < 0.001) in the patients with chronic cholecystitis in the OC group. LC appears to be a safe procedure with a low incidence of complications including bile duct injury when performed by adequately trained surgeons. PMID- 8480883 TI - Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy. AB - To assess the cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy from the payer's perspective, we estimated the probabilities of potential outcomes of each procedure, associated quality-of-life effects, and related direct medical charges and incorporated these estimates into a computerized simulation model. The model projects that laparoscopic cholecystectomy will be more effective than open surgery in terms of total mortality and quality-adjusted survival, for both sexes and all ages. Projected 5 year cumulative charges are lower for laparoscopic cholecystectomy than for open cholecystectomy ($5,354 versus $5,525 for 45-year-old women; $6,036 versus $6,830 for 45-year-old men), and the differences increase substantially with increasing age. We concluded that laparoscopic cholecystectomy is likely to be less costly and more effective than open cholecystectomy for most patients, as long as it does not routinely require preoperative cholangiography and is not associated with increased professional fees or increased risks of retained stones or bile duct injury. PMID- 8480884 TI - The laparoscopic buck stops here! PMID- 8480885 TI - Endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy. AB - Few laparoscopic surgeons currently explore the bile duct at cholecystectomy, which has focused attention on the role of preoperative endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and treatment of duct stones. Indications for ERCP depend on the likelihood of duct pathology; clinical, biochemical, and radiologic predictive factors are well established. Expert endoscopists use ERCP sparingly, only in patients known or very likely to have duct stones, believing that the duct can be cleared after laparoscopic cholecystectomy (LC) when necessary in almost every case. Paradoxically, when the level of local ERCP expertise is modest, ERCP may be attempted before LC more often, thus leaving the option of open exploration if ERCP fails. ERCP is highly efficient in the management of patients with symptoms after LC in order to exclude, diagnose, and treat complications such as retained stones, cystic duct leaks, and strictures. Concern about performing sphincterotomy in young patients (especially those with normal-sized ducts) because of unknown long-term effects is leading some endoscopists to remove small stones through the intact papilla. Selected patients with gallbladder and duct stones may be best treated by endoscopic duct clearance alone, without cholecystectomy (unless or until symptoms develop). Overall, ERCP techniques are currently used in about 10% of patients before or after LC. Each surgical/endoscopic team should develop an algorithm to maximize the effectiveness of the combined approach and to minimize problems. PMID- 8480886 TI - Lithotripsy in the treatment of biliary stones. AB - Noninvasive or minimally invasive techniques for the treatment of biliary stones have been significantly advanced in the past two decades. The least invasive, extracorporeal shock-wave lithotripsy, continues to be used successfully, not only at its earliest reported site of use in Munich, Germany, but also in numerous other centers in the world. Lithotriptors that utilize a spark gap electrode or other sources of energy to generate sound waves and imaging by radiographic and ultrasonographic targeting of stones have proved to be effective in fragmenting biliary stones (90% to 95%) that are too large or otherwise inaccessible to removal by endoscopic papillotomy. Stone clearance (53% to 90%) may require successive treatments and the removal of debris by transendoscopic or surgical means. The mortality is low (0.5%), and the post-treatment course is relatively uncomplicated in an elderly, high-risk group of patients. PMID- 8480887 TI - Role of open choledochotomy in the treatment of choledocholithiasis. AB - In recent years, several less invasive procedures have challenged the preeminence of open choledochotomy in the management of patients with choledocholithiasis. Alternatives now include endoscopic sphincterotomy, extracorporeal shock-wave lithotripsy, percutaneous transhepatic stone extraction, and laparoscopic common duct exploration. In deciding whether an alternative is appropriate for an individual patient, factors to consider include the following: (1) the presence or absence of the gallbladder; (2) the severity of the presenting symptoms; (3) the results of open choledochotomy; and (4) local endoscopic, radiologic, and laparoscopic expertise. Review of available data suggests that endoscopic sphincteroplasty is appropriate for older patients without a gallbladder and for those with severe toxic cholangitis. However, endoscopic sphincterotomy has not been proven to be worthwhile before open surgery. Open choledochotomy has been reported to have a mortality rate of less than 2%, leaving fewer than 5% of patients with retained stones. Since the introduction of laparoscopic cholecystectomy, treatment algorithms for patients with common duct stones have seldom included open choledochotomy. However, future prospective, randomized trials of the management of patients with choledocholithiasis should include open choledochotomy as the gold standard. PMID- 8480888 TI - Laparoscopic approach to common duct pathology. AB - The author reviews his experience with the laparoscopic management of common duct pathology and compares it with the experience of others as reported in the literature. Routine intraoperative cholangiography is advocated. A variety of methods of managing common duct stones laparoscopically is presented. These include balloon-catheter manipulation, fluoroscopically guided basket extraction, and choledochoscopic evaluation and removal of stones. The accumulated experience indicates that more than 90% of common duct stones can be removed laparoscopically via the cystic duct. This approach significantly reduces the need for either preoperative or postoperative endoscopic retrograde cholangiopancreatography. Although laparoscopic choledochotomy has been employed in a number of cases and can be performed with a high degree of safety and efficacy, it is needed only infrequently. This form of management results in decreased dependence upon T-tubes, thereby reducing postoperative morbidity and the length of hospitalization. A rational protocol for the management of common duct pathology is presented. PMID- 8480889 TI - Exposure, dissection, and laser versus electrosurgery in laparoscopic cholecystectomy. AB - The technical complications of laparoscopic cholecystectomy occur while creating the pneumoperitoneum, placing trocars, obtaining exposure, and performing the initial dissection of the cystic duct and artery. The errors most feared are intestinal injury, vascular injury, and common bile duct injury. Bile duct injury usually results from the misinterpretation of the extrahepatic biliary anatomy. Confusion is most likely if the gallbladder infundibulum is pushed superiorly and medially, pulling the common bile duct out from behind the duodenum and into line with the cystic duct and gallbladder. Other dissection errors resulting in bile duct injury include the failure to begin dissection on the gallbladder, routine dissection of the cystic duct all the way to the common bile duct, failure to identify anomalies of the cystic and hepatic ducts, failure to open all folds of the gallbladder infundibulum, and entrapment of a narrow common bile duct by a cystic duct clip "slid" too far proximally. Proper dissection strategy includes posterolateral traction on the gallbladder infundibulum and initiation of dissection at the most medial point where the gallbladder is clearly seen. Pedunculation of the gallbladder will reveal most ductal anomalies but should be supplemented with routine digital fluoroscopic cholangiography. The controversy over optimal sources for thermal dissection of the gallbladder has largely been resolved. Electrosurgical dissection is a more rapid, hemostatic, and economical dissection. PMID- 8480890 TI - Gallbladder and gallstone removal, open versus closed laparoscopy, and pneumoperitoneum. AB - Surgeons need to be aware of the various options available to remove enlarged gallbladders or gallstones lost during laparoscopic cholecystectomy. Every attempt should be made to recover stones that have escaped from a ruptured gallbladder during laparoscopic cholecystectomy, short of converting to laparotomy. Initial access to the peritoneal cavity can be safely accomplished using either a closed or an open technique. Ideally, surgeons should become facile with both procedures. Carbon dioxide (CO2) gas has emerged as the most practical agent for pneumoperitoneum during laparoscopic cholecystectomy. Surgeons should be knowledgeable about the physiologic and pathologic effects of CO2 gas. PMID- 8480891 TI - Routine versus selective intraoperative cholangiography. AB - Since its introduction 60 years ago, intraoperative cholangiography (IOC) has reduced the incidence of unnecessary common bile duct (CBD) explorations from 66% to less than 5%. However, the use of routine IOC during cholecystectomy remains controversial. Routine IOC during laparoscopic cholecystectomy reduces the incidence, level, and severity of bile duct injuries. Performing routine IOC with CBD exploration eliminates the need for postoperative endoscopic retrograde cholangiopancreatography or endoscopic sphincterotomy in the 1.4% to 3.5% of postoperative patients with abdominal pain or retained stones, thereby also eliminating the need for reoperation after failed endoscopic sphincterotomy. The financial cost of routine IOC is equal to or less than the cost of treating the severe bile duct injuries that are prevented as well as the cost of the work-up and treatment of patients with retained stones who have not had IOC. A policy of routine IOC sets operative priorities and improves the surgical skills that are necessary for laparoscopic transcystic duct CBD exploration. PMID- 8480892 TI - Laparoscopic management of acute cholecystitis. AB - The role of laparoscopic surgery in patients presenting with acute cholecystitis remains controversial. From September 1989 through August 1992, a total of 720 patients underwent cholecystectomy. Ninety-six were unplanned admissions with a clinical diagnosis of acute cholecystitis. Laparoscopic surgery was attempted in 83 patients. Thirteen individuals were not offered laparoscopy because of the surgeon's inexperience. Twenty-two (27%) patients required the laparoscopic procedure converted to an open laparotomy. The mean postoperative hospital stay for patients undergoing laparoscopic cholecystectomy was 3.3 days versus 6.8 days for the laparotomy group. There was no mortality and no bile duct or major vascular injuries in either group. The overall operative morbidity rate was 16.9%. Laparoscopic cholecystectomy appears to be a safe and beneficial option in selected patients with acute cholecystitis. A low threshold for conversion to laparotomy appeared to be an important factor in maintaining a low incidence of operative complications. Several modifications to the technique of laparoscopic cholecystectomy have evolved over the 3-year study period and are described. PMID- 8480893 TI - Surgery for gallstone pancreatitis. AB - Operative intervention during an attack of biliary pancreatitis is an effective way to treat the associated biliary tract disease and prevent the development of future attacks. Laparoscopic cholecystectomy has now emerged as the procedure of choice to treat cholelithiasis, but the treatment of associated choledocholithiasis is not yet defined. There are currently two possible approaches to these patients: First, early endoscopic retrograde cholangiopancreatography (ERCP) to determine if stones are present within the bile duct and, if so, early endoscopic sphincterotomy. If this approach is followed, then laparoscopic cholecystectomy should be performed as soon as the acute symptoms have subsided. On the other hand, if ERCP is not performed early and there are no obvious signs of biliary obstruction, laparoscopic cholecystectomy should probably be performed just before the patient is discharged. By waiting 5 to 6 days after the onset of the attack, the chances of finding associated choledocholithiasis are minimized. At the time of laparoscopic cholecystectomy, a cholangiogram must be obtained. If choledocholithiasis is found, the common bile duct may be explored via laparoscopic techniques, the operation may be converted to an open procedure, or the patient may be scheduled for endoscopic sphincterotomy for the next day. PMID- 8480894 TI - Role of endoscopy in gallstone pancreatitis. AB - Early identification of those patients presenting with acute pancreatitis due to gallstone disease is important since emergency intervention may prevent the development of local and systemic complications. Urgent biliary surgery carries unacceptably high morbidity and mortality rates, but endoscopic retrograde cholangiopancreatography in experienced centers appears to be safe and is the optimal method for the diagnosis of bile duct stones. Two randomized controlled prospective trials have shown an advantage for endoscopic sphincterotomy and bile duct clearance compared with supportive therapy when performed within 24 to 72 hours of admission in those patients whose symptoms are considered severe according to prognostic scoring systems. PMID- 8480895 TI - Effect of nonbiliary problems on laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy may be performed safely in most patients with symptomatic cholelithiasis. There are few absolute contraindications to laparoscopic cholecystectomy. Many relative contraindications exist, which relate to the surgeon's experience and the ability of the operating team to manage potential complications. Preoperative evaluation should assess the potential nonbiliary problems that affect the performance of laparoscopic cholecystectomy, including severe cardiopulmonary disease, coagulopathy, cirrhosis, and pregnancy. Since most therapeutic laparoscopic procedures are currently performed with a carbon dioxide (CO2) pneumoperitoneum, the physiologic effects of the elevated abdominal pressure and absorbed CO2 must be understood by the surgeon. Specific nonbiliary problems addressed in this review are cardiopulmonary disease, hypercortisolism, cirrhosis and portal hypertension, morbid obesity, previous abdominal surgery, and pregnancy. PMID- 8480896 TI - Complications of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy is a safe and effective treatment of cholelithiasis in experienced hands. Mortality is rare. The Southern Surgeons Club data and several other recent large series indicate that major complications occur in less than 3% of patients. The most significant common complication is injury to the bile duct, for which the greatest risk factor is inexperience. Major biliary injury usually requires reoperations. Roux-en-Y hepaticojejunostomies, often multiple, are usually necessary for repair. The popularity of this technique continues, and further efforts should be focused on elimination of the learning curve for major biliary injury. If injuries do occur, they should be recognized early, and patients should be referred to centers experienced in their treatment. PMID- 8480897 TI - Complications after laparoscopic cholecystectomy. AB - After becoming alarmed about seven unusual and severe complications reported by New York State hospitals after laparoscopic cholecystectomy, the Department of Health of New York State tabulated all reported adverse incidents. After observing unusual injuries to the great vessels of the abdomen and an increase in major bile duct injury during laparoscopic cholecystectomy, the Department of Health prepared a memorandum to New York State hospitals advising closer attention to education, credentialing, proctoring, and outcome after these operations. The frequency of cholecystectomy has increased sharply, by 21%, since the advent of laparoscopic cholecystectomy. The serious injury rate may be approximately 15 times that observed after an open cholecystectomy. Recognizing the theoretic advantages of the procedure, the Department of Health reminded hospital Boards of Trustees of their obligation to establish mechanisms for credentialing and privileging surgeons and surgical teams so that the risks do not exceed those expected of the open procedure and to detect and correct deviations from this standard. PMID- 8480898 TI - Registry of laparoscopic cholecystectomy and new and evolving laparoscopic techniques. AB - To collect information on the rapid application of laparoscopic surgery, the National Laparoscopic Surgery Registry surveyed more than 4,000 of the 16,000 currently practicing laparoscopic surgeons. Preliminary analysis of the data has revealed that most of the respondents had been trained in general surgery, but a small percentage were certified only in surgical subspecialties. Surgeons acquiring skills in laparoscopic surgery had various levels of experience ranging from less than 1 year to more than 38 years in surgical practice. Nearly 90% of the respondents attended a laparoscopic cholecystectomy course with hands-on training. In those courses, an average of 16 hours was devoted to animal laboratories for acquisition of skills. Additional training in the form of a preceptorship is being undertaken by an increasing number of surgeons. The future of minimally invasive surgery is being supported by rapid advances in technology. New video systems capable of displaying three-dimensional images and miniaturized fiberoptic scopes are now available. Computer enhanced three-dimensional ultrasound images provide the surgeon with the ability to examine the content and consistency of tissues in addition to their appearance. Advances in mechanical retraction may eliminate the need for carbon dioxide insufflation of the abdomen. Tissue repair using tissue glues or laser-mediated processes may reduce the need for endocavitary suturing. These advances in technology and techniques may reduce the morbidity and mortality of these surgical procedures and, ultimately, improve the standard of care for surgical patients. PMID- 8480899 TI - [The role of clonidine in anesthesia]. AB - For decades the adrenergic alpha2 agonist clonidine has been considered to be one of the classical, centrally acting antihypertensive agents. In addition to its antihypertensive and sympathicolytic effects, in recent studies clonidine has been demonstrated to be an effective sedative and analgesic and to reduce the amount of anaesthetic agents required. Therefore, a reconsideration of possible new indications for clonidine in clinical anaesthesiology seems to be justified. This paper presents the pharmacological basis for treatment with clonidine and reviews the extensive literature on its clinical indications in anaesthesia. Clonidine apparently produces its sedative and anaesthetic-sparing effects by stimulation of centrally located alpha2 adrenoceptors. Analgesia seems to be mediated mainly by activation of alpha2 adrenoceptors in the dorsal horn of the spinal cord. Considering its clinical indications, clonidine is often used as a supplement in the treatment of alcohol withdrawal syndromes. Future indications for clonidine may be the treatment of postoperative shivering and chronic pain management. Administration of clonidine in combination with a local anaesthetic prolongs analgesia and motor blockade. Its use in premedication and postoperative pain management may be limited by its principal effects of hypotension and bradycardia. In future, cardiovascular side effects may be minimized if all the subtypes of alpha2 adrenoceptors, their distribution within the central nervous system, and their specific action are clearly defined. This could result in a detailed therapeutic index of more selective and potent alpha2 agonists. PMID- 8480900 TI - [Topographic-quantitative EEG-analysis of the paradoxical arousal reaction. EEG changes during urologic surgery using isoflurane/ N2O anesthesia]. AB - Increases in slow-wave (delta) activity in the EEG may reflect increased depth of anaesthesia provided that hypoxia, haemodynamic instability and drug overdose have been excluded. In contrast, similar intraoperative EEG responses have been described as paradoxical arousal reactions. The aim of this study was to assess the effects of surgical stimulation on spatial EEG changes during anaesthesia with 0.6% isoflurane/66% nitrous oxide. METHODS. The present study investigated changes in EEG power and frequencies in 20 patients (mean age 36 +/- 8 years; ASA I or II) scheduled for elective urological surgery during steady-state anaesthesia with 0.6% isoflurane and 66% nitrous oxide. The following variables were measured: heart rate (HR), mean arterial blood pressure (MAP), end-tidal isoflurane (PetISO) and carbon dioxide concentrations (PetCO2), arterial oxygen saturation (SaO2%) and body temperature (degree C). Patients were randomly assigned to one of two groups: group 1 (n = 10; without surgery) and group 2 (n = 10; with surgical procedure). The EEG was recorded over 20 min. The first 5 min were taken as baseline. In group 2 surgical stimulation (skin incision with subsequent surgical preparation) was started 1-2 min after recording of baseline values. Topographical distribution of EEG output was recorded from 17 electrodes (international 10-20 system), digitized and stored on disk (CATEEM) after establishment of steady-state anaesthesia (PetISO: 0.6%; PetCO2: 35-37 mmHg). Data are given as medium (microV2/Hz) and relative changes (%) +/- SD with respect to baseline. Statistical significance was tested for F4 versus C4 for the delta- and alpha-1-frequency bands using Wilcoxon's test (P < 0.05). RESULTS. In group 1 (without surgical stimulation) all parameters did not change over time. EEG slowing with an increase in power (> 100%) was noted in 8 patients of group 2 (n = 10; during surgical stimulation). By visual inspection of the original EEG tracings paradoxical arousal patterns were seen in these patients. In group 2, delta output changed from 69.6 microV2/Hz (baseline) to 147.4 microV2/Hz at frontal leads (F4) 5-6 min after the start of surgery. Only minimal changes were observed for theta activity. At the same time, in most cases fast wave activity (alpha 1, alpha 2, beta 1 and beta 2) was decreased by more than 50% at identical cortical areas. Increases in MAP were noted continuously after start of surgery up to a maximum of 19.8% from baseline, which became significant at the 16-min level. Heart rate did not change over time. DISCUSSION. Our data demonstrate that EEG slowing may be induced by surgical stimulation during steady-state anaesthesia with 0.6% isoflurane/66% nitrous oxide in oxygen. These findings are consistent with previous reports indicating the occurrence of slow wave patterns following sensory stimulation in comatose patients. Since these events occur predominantly at frontal areas they may not be detected with single-channel parietal recordings. Our data suggest that topographical EEG monitoring may useful for assessing painful events during surgery. Using EEG monoparameters like spectral edge frequency or median the occurrence of paradoxical arousal reactions may be falsely interpreted as an increased depth of anaesthesia. PMID- 8480901 TI - [Propofol, isoflurane and neuroleptanesthesia. Ophthalmic surgery in geriatric patients]. AB - Ophthalmic surgeons require anaesthesia to ensure that the patient is completely relaxed for microsurgical operations and that the intraocular pressure is reduced. These conditions must be maintained throughout the operation. In addition to these requirements, the anaesthetist mostly deals with elderly patients with multiple diseases. Although earlier studies have shown which general or local anaesthesia is preferred for which patients and operations, studies on which general anaesthesia technique is ideal to fulfil these requirements are still lacking. The aim of this study was to show which technique causes the least stress for a geriatric patient undergoing an ophthalmic operation, propofol/fentanyl anaesthesia, isoflurane anaesthesia or neuroleptanaesthesia. PATIENTS AND METHODS. Sixty patients aged 60 years and above were included in this study. After being randomly allocated to either propofol/fentanyl (continuous propofol infusion), isoflurane or neuroleptanaesthesia, they underwent ophthalmic surgery. Intraoperative complications (cardiocirculatory changes) and surgical conditions were recorded. After the operation, patient vigilance and post-operative pain reactions (nominal pain score) were assessed over 8 h by means of simple reaction tests and the Juhl index. Within the first 2 h after surgery, cardiocirculatory changes were also documented and arterial blood gases measured. RESULTS. The treatment groups did not differ with respect to general biometric data, preoperative risk or operations carried out. Intraoperative cardiocirculatory changes and the resulting therapy (positive inotropic drugs, volume replacement fluids) were similar in all groups. The surgical conditions were equally good in all groups. Apart from a lower rate pressure product in the first 60 min after propofol/fentanyl anaesthesia, there were no postoperative differences in cardiocirculatory parameters or blood gases. After isoflurane anaesthesia the time until the patients were able to give their names and perform the finger-nose test properly was longer than that after neurolept-anaesthesia or propofol anaesthesia. After propofol anaesthesia the patients could perform simple tests earlier and were more alert over the whole monitoring period than after isoflurane or neuroleptanaesthesia. On the other hand, the patients in the neuroleptanaesthesia group had fewer pain complaints than those in the two groups compared. DISCUSSION. None of the anaesthesia techniques used in this study showed an intraoperative advantage. This is not surprising since all anaesthetics, with the exception of ketamine, reduce intraocular pressure. The prerequisite, however, is careful monitoring of anaesthesia in elderly patients in order to avoid cardiocirculatory changes, mild hyperventilation and coughing and pressing at the end of the operation. Until this point in time no change in the depth of anaesthesia is allowed. Therefore, it seems on the whole that there are benefits from propofol-fentanyl anaesthesia because of the fact that in comparison with the rather techniques, elderly patients become alert again faster. However, sufficient postoperative pain therapy is necessary to free the patients of pain to the same degree as with neuroleptanaesthesia. In most cases peripherally acting analgesic substances with no interference with vigilance are sufficient. PMID- 8480902 TI - [Halothane absorption by dry soda lime]. AB - Humidified soda lime is commonly used to eliminate carbon dioxide from the circulatory system. Little is known about adverse reactions to accidentally dried soda lime. Therefore, a case of unexpected absorption of halothane by dry soda lime is reported. These observations were confirmed by a simulation with relevance to anaesthetic practice. CASE REPORT. A 46-year-old ASA class I patient was scheduled for elective surgery. After induction of general anaesthesia with 500 mg thiopentone, followed by 100 mg suxamethonium, the trachea was intubated. The patient was ventilated with nitrous oxide in oxygen and 1.5 vol% of halothane for several minutes in the induction room. After being connected to a new circulatory system in the operating theatre, the patient was ventilated but, in addition inspiratory and expiratory anaesthetic gas concentrations were measured. Despite a vaporizer position of 1.5 vol% the inspiratory concentration of halothane was below 0.2 vol%. Disconnecting the tube, the typical odour of halothane was missing in the inspiratory line of the circulatory system, but was present in the fresh gas tube. Furthermore, the lower part of the soda lime canister was surprisingly hot. After removing both the absorbers, the inspiratory halothane concentration immediately normalized. The absorbers were replaced by canisters filled with fresh soda lime, and the anaesthesia was terminated without further complications. An absorption of halothane by dried soda lime was suspected. METHODS OF SIMULATION. In the first simulation four circulatory systems with two soda lime canisters each were perfused with 21 of oxygen for 48 h. In the second simulation four soda lime canisters placed in one circulatory system were perfused with 1 l for 120 h. For measurement of halothane absorption each canister was placed in a circulatory system. The canister was perfused with a fresh gas flow of 2 l of oxygen and a vaporizer position up to 1.3 vol% of halothane. By the time an equilibrium was reached, i.e., in- and outflow concentrations of halothane were equal for a 3-min period, further halothane vaporization was stopped. In a 30-s interval the soda lime temperature and the gas concentration entering and leaving the soda lime canister were registered. Subsequently, the humidity of the soda lime was determined. RESULTS. In the first simulation 6 of the 8 canisters showed a humidity of soda lime of 15.5% of 19%, with halothane being absorbed in one case. Normally, the equilibrium between in- and outflow gas concentration was reached after 3.5-4 min. In the remaining two canisters the humidity was 14% and 9%. Only a small amount of halothane vapour was absorbed. The halothane concentrations were in equilibrium after 10 to 13 min. The probes from the second simulation revealed a humidity of soda lime of 2% to 8.7%. Below a humidity of 4% the concentration of halothane leaving the canister was greatly reduced. It took 63 min to reach a steady state in the 2% humidity probe and the temperature rose to 43.1 degrees C. CONCLUSIONS. Accidental perfusion of the circulatory system with dry oxygen can cause a reduction in the humidity of soda lime. Dried soda lime delays the increase of halothane concentration in the inspiratory limb. The absorption of halothane is accompanied by an increase in the temperature of the soda lime. Therefore, in every situation lacking a sufficient anaesthetic level during inhalation anaesthesia, absorption of the vaporized anaesthetic must be excluded. Only dried soda lime can absorb halothane. PMID- 8480903 TI - [The effect of age on the spread of spinal anesthesia using isobaric 2% mepivacaine]. AB - In the elderly, anaesthesia and surgery are associated with higher perioperative mortality and morbidity as compared to younger patients. There is some evidence that spinal anaesthesia may improve the postoperative state of elderly patients. A prospective study was performed to elucidate the effects of age on the characteristics of spinal anaesthesia with isobaric 2% mepivacaine. METHODS. Forty-six patients aged between 17 and 39 years and 48 elderly patients aged between 76 and 87 years having operations on the lower extremities or lower abdomen were investigated. All patients received 4.5 ml plain mepivacaine 2% (90 mg) as a subarachnoid injection in the L3-4 interspace in the sitting position. The patients were turned supine immediately after the injection. Time of onset, extent and duration of analgesia, motor block, and cardiovascular responses were assessed. The segmental level of sensory loss was tested using the pin-prick method. RESULTS. It was found that the time to maximal motor blockade was significantly decreased in the older age group compared to the younger group (7.9 vs 11.5 min). In the older group, the time to maximum spread was significantly shorter (11.4 vs 13.6 min). A significantly higher sensory block was obtained in the older group (T8 vs T10). The mean duration of analgesia or motor blockade did not differ significantly (200.7 vs 192.8 min). There were no unacceptably high degrees of spinal blockade. In the older group there was a tendency to a greater decrease in systolic arterial pressure as compared to preanaesthetic values (23.7% vs 16.3%) and greater falls in diastolic blood pressure were observed in the older group (22.1% vs 14.4%). A greater volume of lactated Ringer's solution was necessary in the older group (14.8 vs 10.3 ml/kg). Postspinal headache was encountered in 3 patients in the younger group and 2 in the older group. DISCUSSION. It is concluded that there was a tendency for greater spread of spinal analgesia with isobaric 2% mepivacaine in the elderly. The clinical significance of this finding is limited. In elderly patients hypotension is more common than in younger patients, but might not be related solely to age or extent of the neural blockade. PMID- 8480904 TI - [Analysis of the therapy of chronic pain. A comparison of previous therapy and specialized pain therapy]. AB - In Germany patients with chronic pain are often undertreated. It is necessary to establish more specialized institutions for pain therapy. As pain therapy is time consuming and labor intensive the costs must be justified by quality and efficiency. METHODS. We analyzed the new patients who came to our pain clinic in 1990 and compared the previous nonspecialist pain-related treatment with our pain therapy. For each patient we recorded the duration of pain therapy in the past, the number of physicians involved in the treatment, the number and duration of hospital stays and the number of operations carried out to relieve pain. For our pain therapy we recorded the number of treatments on an outpatient basis, the number of patients who were hospitalized and the number of hospital days. The outcome of our pain therapy was determined on a visual analogue scale (VAS). Pain relief of more than 50% was defined as adequate pain therapy. RESULTS. In 1990 we treated 379 new patients in our pain clinic. The largest group (140, 37%) had pain of the muscle or skeletal system. A further 75 patients (18%) had neuropathic pain, 66 (17%) suffered from cancer pain, several types of headache were found in 57 patients (15%), 19 patients (5%) had phantom limb pain, 11 (3%) suffered from reflex sympathetic dystrophy, and we diagnosed psychogenic pain in 11 patients (3%). On average the patients had been treated for their pain over a period of 10 years by eight different physicians. Patients suffering from migraine had the longest duration of preliminary therapy (19.2 years), while patients with cancer pain were pretreated for 2, 3 years in the period before. 80% (n = 302) of all patients were hospitalized at least once. A total of 20,959 hospital treatment days was registered. At least one operation was performed in 34% of the patients (n = 130) to relieve the pain. For all patients the pain relief afforded by the preliminary therapy was insufficient. In our pain therapy the patients had on average 6.5 outpatient appointments. We hospitalized 45 patients (12%), for a mean of 11 days. During the observation period 74% of the patients (n = 280) obtained pain relief of more than 50% in comparison with the start of treatment. CONCLUSION. The findings of our retrospective study demonstrate that specialized pain therapy is evidently effective. If such therapy is instituted early enough, chronic pain can be prevented. Shorter duration of disease, fewer stays in hospitals and less absence from work could reduce the economic costs of chronic pain. It is necessary to make specialised pain therapy a regular component of clinical practice; this means redoubling our efforts concerning education and experimental and clinical studies. The efficiency of pain therapy must be documented in order to improve the care of patients with chronic pain. PMID- 8480905 TI - [Inhaled nitric monoxide. Application and continuous measurement of concentration]. AB - Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that may be useful in the treatment of patients with severe pulmonary hypertension. We describe a delivery system of inhaled NO that allows safe application and continuous measurement of the inspired NO concentration during mechanical ventilation. From a gas cylinder containing NO in N2 (600 ppm NO), an adjustable amount of gas is introduced into the inspiratory side of the tubing system via a pressure reduction valve, a magnetic valve, and a special injection nozzle. The NO concentration is diluted to the desired value by the tidal volume. The magnetic valve is connected to the ventilator and opens at the beginning of each inspiration and closes after a predetermined time. The gas volume is proportional to the pressure at the magnetic valve and the opening time. To monitor the inspiratory NO concentration, a specimen of gas is taken from an angle-connector and passed over an electrochemical sensor. The second nozzle of the sensor is connected to a water seal, which is adjusted to the positive end-expiratory pressure level of the ventilator to insure that the gas flow over the sensor is limited to inspiration. PMID- 8480906 TI - [Myxedema coma as a rare postoperative complication]. AB - Myxedema coma is characterized by severe lack of thyroid hormones, unconsciousness and serious restriction of vital functions. The mortality rate still ranges between 50 and 80%. In patients with inapparent hypothyroidism myxedema coma occasionally follows surgery, anesthesia or severe infection. A case of myxedema coma following surgery is reported. CASE REPORT. A 46-year-old woman was anesthesized for hip replacement. The intraoperative cardiovascular situation was characterized by hypotension and tachycardia. On the first postoperative day, unexpectedly a cardiac arrest occurred. Resuscitation with high doses of epinephrine was successful. There was no evidence of myocardial infarction, hypoxia and pulmonary embolism as causative factors for cardiac arrest. A pulmonary artery catheter was inserted and showed low cardiac output. Catecholamines and intravascular fluids were administered without hemodynamic improvement. In the next 5 days pneumonia was followed by ARDS and acute renal failure. After successful treatment of these complications the patient remained in deep coma. An intracerebral disease could be excluded by computerized tomography. Evaluation showed low thyroid hormones (T3; T4) and elevated TSH. The diagnosis of a myxedema coma was assumed. After failure of oral therapy with L thyroxine (0.025-0.05 mg/day) for 10 days, intravenous therapy with 0.5 mg L thyroxine was performed. Thirty-six hours later the patient regained consciousness, without cardiac complications. The patient progressed uneventfully under oral therapy with 0.1 mg L-thyroxine and was discharged from the hospital 6 weeks later. DISCUSSION. Pathophysiology and symptomatology of a case of postoperative myxedema coma are described (Tables 1-4). In this patient, the following symptoms occurred: low thyroid hormones (T3; T4), elevated TSH, deep coma, decreased ventilatory response to CO2, diminished myocardial contractility under catecholamine stimulation, impaired renal water excretion. After failure of oral substitution of L-thyroxine, intravenous therapy had to be performed in spite of the high risk of further cardiac complications in this patient. This led to complete recovery with normal neuropsychological and cardiopulmonary parameters. CONCLUSION. Myxedema coma is a rare complication in postoperative care, but in cases of inexplicable unconsciousness thyroid failure should be excluded. If myxedema coma is evident, intravenous therapy with L-thyroxine should be performed under the conditions of extended monitoring. PMID- 8480907 TI - [Comments on the paper by K.A. Lehman and K.H. Krauskopf. Intraoperative consciousness during balanced anesthesia]. PMID- 8480908 TI - [Forensic aspects of blood transfusions]. PMID- 8480909 TI - Organic-phase biosensors for monitoring phenol and hydrogen peroxide in pharmaceutical antibacterial products. AB - Organic-phase biosensors open new opportunities for assays of challenging pharmaceutical products. Such opportunities are illustrated for the rapid determination of phenol and peroxide antiseptics in different anti-infective formulations. The tyrosinase and peroxidase enzyme electrodes offer reliable quantification of these antibacterial agents following sample dissolution in the organic solvent. The dynamic properties of these enzyme electrodes are exploited for rapid and reproducible flow-injection assays of the pharmaceutical products (relative standard deviation = 1.6-1.9%). Such developments should facilitate rapid quality control testing in the pharmaceutical industry and should be applicable to other therapeutic agents and products. Applicability to cosmetic products containing hydrogen peroxide is also demonstrated. PMID- 8480910 TI - Agarose gel electrophoresis system for the separation of antibiotics used in animal agriculture. AB - A novel electrophoresis system using agarose gel has been developed for the separation and as an aid in the classification of antibiotics. This system utilizes Nunc cell factory disposable tissue culture dishes, which serve as bioassay dish and cooling chamber for agarose gel, in a custom designed electrophoresis unit. Tris(hydroxymethyl) methylamine-succinate buffer at pH 6.0 and 8.0 are employed as the electrolyte for electrophoresis. Bioautography was used as the indicator of mobility. Any agar diffusion assay can be modified to use this system. A suggested name for this system is Nunc cell factory agarose gel electrophoresis (NUAGE). Selected antibiotics, representative of the aminoglycoside, beta-lactam, macrolide, moenocinol, peptide, polyene, polyether, quinone and tetracycline classes, were separated with this system. PMID- 8480911 TI - Echocardiographic Doppler evaluation of left ventricular diastolic function in athletes' hypertrophied hearts. AB - It is well known that one of the most evident effects of prolonged and intense physical training is an increase of left ventricular mass. This increase could have a great influence on the diastolic properties of the heart, which can now be accurately evaluated by use of pulsed- and continuous-wave of Doppler echocardiography. The aim of this study was to evaluate the diastolic function of a group of superendurance athletes (professional bicyclists, exercising more than forty hours a week). Sixteen athletes (A), aged between twenty and thirty-one years, during the period of maximal training, and 16 age-matched controls (C) were studied. All subjects were evaluated at rest with mono-dimensional, two dimensional, and Doppler echocardiography. Diastolic (DD) and systolic (SD) diameter, posterior wall (PW), and interventricular septum (IVS) thickness were also measured. The left ventricular mass (LVM) was calculated. Diastolic function was evaluated by calculating isovolumetric relaxation time (IVR) with continuous wave Doppler, and deceleration time (DT), rapid filling flow peak (Ep), and atrial filling peak (Ap) were evaluated with pulsed Doppler echocardiography. The LVM (A: 354 +/- 47 g vs C: 170.6 +/- 33.4, p < 0.05), DD (A: 57.7 +/- 3.9 mm vs C: 50.5 +/- 2.7, p < 0.01), PW thickness (A: 11.9 +/- 0.7 mm vs C: 8.4 +/- 0.6, p < 0.05), and IVS thickness (A: 12.3 +/- 1 mm vs C: 8.2 +/- 0.9, p < 0.05) were significantly greater in the athletes than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480912 TI - Comparison of treadmill walking and stair climbing over a range of exercise intensities in peripheral vascular occlusive disease. AB - Although claudication pain and hemodynamic responses to exercise are related to the degree of arterial narrowing in the lower extremities, the nature of these responses to different exercise tasks and intensities is less clear. Thus, the purpose of this study was to compare claudication and hemodynamic responses to graded walking, level walking, and stair climbing over a range of exercise intensities. Ten patients with peripheral vascular occlusive disease performed five tests within each of the three exercise tasks. Similar values of oxygen consumption were obtained among exercise tasks at each intensity (p = ns). Time to onset of claudication pain and to maximal pain were similar among exercise tasks (p = ns), and both demonstrated a curvilinear decrease as intensity increased (p < 0.05). Foot transcutaneous oxygen tension, ankle systolic blood pressure, and ankle/brachial systolic pressure index were also similar among the three exercise tasks (p = ns); however, each decreased linearly as exercise intensity increased (p < 0.05). Thus, in peripheral vascular occlusive disease, the imbalance between oxygen delivery to the exercising lower extremity musculature and the local metabolic demand is similar during different weight bearing activities. Second, even though the peripheral circulation is progressively impaired with increased exercise intensity, anaerobic metabolism in the ischemic lower extremity musculature may prevent a continual decline in claudication times. The clinical implication is that a more thorough assessment of the functional limitations imposed by claudication pain is not obtained by using different types of weight-bearing exercise tests as opposed to using on ly one type. PMID- 8480913 TI - Risk factors for varicose disease before and during pregnancy. AB - Risk factors for varicose disease before and during pregnancy have been analyzed by use of data from a survey on venous disease in pregnancy conducted in 611 women (mean age thirty years, range fifteen to forty-seven) who consecutively delivered at the Obstetric-Gynecologic Clinic "L. Mangiagalli" of Milan between January and April, 1989. In total, 137 women (22%) reported varicose disease before the index pregnancy. The relative risk (RR) of varicose disease before the index pregnancy increased with age, being, as compared with women aged twenty nine years or less, 1.6 in those aged thirty to thirty-four and 4.1 in those aged thirty-five years or more (chi 2(1) trend 25.28, p < 0.001). Compared with nulliparae, women reporting a full-term pregnancy before the index pregnancy had an RR of venous disease of 1.2, and the risk increased to 3.8 in women reporting two or more births (chi 2(1) trend 25.28, p < 0.001). A family history of varicose disease was associated with an RR of venous disease of 6.2 (95% confidence interval, CI, from 4.1 to 9.6). No relationship emerged between varicose disease and overweight. Of the 474 women who did not report venous disease before the index pregnancy, 132 (28%) developed venous disease during the index pregnancy. The risk of developing venous disease in pregnancy increased with age, being, as compared with women aged twenty-four years or less, 4.0 in those aged thirty-five years or more, and the trend in risk was statistically significant (chi 2(1) trend 16.25, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480914 TI - Types of basilar artery syndrome: clinicoradiologic correlation. AB - Twenty-two patients with ischemic stroke, as a single event, in the territory of basilar artery (BA) are reported. On the basis of the findings from computerized tomography (CT) and clinico-radiologic features, the authors propose that this heterogeneous entity--the basilar artery (BA) syndrome--can be divided into five subtypes. Type 1 (complete type), characterized by infarctions in the whole territory of BA, is incompatible with life; type 2, with extensive brain stem infarct, may result in a locked-in state; and type 3, with infarctions in part of the BA territory (incomplete form or "partial syndrome") may have a more variable clinical outcome. However, type 4, with a top of the BA syndrome, and type 5, with negative CT BA syndrome (angiographically verified), are often more benign. Although initial CT scanning may infrequently be unrevealing, serial and follow up CT scannings have proven their usefulness in the majority of cases as a noninvasive tool, in contrast to cerebral angiography, for predicting the short term prognosis of BA syndrome. PMID- 8480915 TI - Transesophageal echocardiography for detecting intracardiac thrombi in embolic stroke. AB - The authors studied 56 patients with cardioembolic stroke to search for intracardiac thrombi by use of transesophageal and transthoracic echocardiography. Forty consecutive patients were examined within four weeks of stroke onset and the remaining 16 in the chronic stage. They also performed ultrafast computed tomography in 9 of them. Underlying heart disease was present in all subjects. Anticoagulant therapy had already been started in 29 at the time of examinations. Using their own criteria for echocardiography, they diagnosed intracardiac thrombus in 7 cases and valvular vegetation in 1. Six thrombi were located in the left atrial appendage, 4 of which were smaller than 10 mm in diameter. These small thrombi were not found by either transthoracic echocardiography or computed tomography. Transesophageal echocardiography appears to be superior to the other two methods, especially for detecting small intracardiac thrombi in the left atrial appendage. PMID- 8480916 TI - Plasma, serum and whole-blood viscosity variations with age, sex, and smoking habits. AB - To study the influence of age, sex, and smoking habits on rheology, the authors measured plasma (PV), serum (SV), native (NBV), and corrected (CBV) blood viscosity with a computerized rotational viscometer in 152 blood donors (86 men and 66 women) and in 20 healthy persons (4 men and 16 women) attending smoke aversion treatment. None of the viscosity measures or erythrocyte sedimentation rate changed significantly with age, whereas hematocrit (HC) and fibrinogen concentration (FC) both increased with ageing (p < 0.05 and p < 0.001, respectively). Higher (p < 0.001) values of NBV and HC were found in men than in women, whereas higher values were found in women than in men for FC (p < 0.01) and ESR (p < 0.001). In blood donors, moderate smoking (mean twelve cigarettes/day) significantly influenced only ESR, which was higher (p < 0.001) in smokers than in nonsmokers. In heavy smokers (mean twenty-one cigarettes/day), however, higher (p < 0.001) PV, SV, and NBV were found, as well as higher (p < 0.01) FC and HC as compared with nonsmoking blood donors. PMID- 8480917 TI - Behcet's disease in the etiology of Budd-Chiari disease. AB - Hepatic venous outflow obstruction (Budd-Chiari syndrome-BCS) was diagnosed in 30 patients during the period from March, 1987, to May, 1991, in Hacettepe University Hospital, Turkey. Patients with Behcet's disease constituted the major group (12/30) in the etiologic distribution. Although the vascular manifestations of Behcet's disease, including venous and arterial occlusions, varices, and aneurysms, are well known, the hepatic vein involvement has been reported in only 22 cases in the literature so far. The authors present 30 cases of BCS, of whom patients with Behcet's disease comprise the largest group (40%). The angiographic findings are not specific to Behcet's disease. It is noted, however, that inferior vena cava involvement is more common in these patients (83.3%) than it is in the rest of the group (61.1%). It is suggested that Behcet's disease should be included among the diagnostic possibilities in a case of BCS, particularly in the countries in which it is prevalent. PMID- 8480918 TI - Primary muscular hydatid cyst causing arterial insufficiency: case report and literature review. AB - Hydatid disease, though known to occur in most organs and areas of the body, is extremely rare in skeletal muscle. In this article the authors present a case of a primary muscular hydatid cyst, originating from the adductor muscle group, causing obstruction of the femoral artery and vein. PMID- 8480919 TI - Renovascular hypertension caused by lymph node metastasis in a patient with uterine cervical cancer: case report. AB - Renovascular hypertension was found in a fifty-four-year-old woman who had been diagnosed as having uterine cervical cancer, stage Ib, six months before admission. Renal arteriography showed a stenosis of the right renal artery with a significant increase in renal vein renin level from the ipsilateral kidney. Abdominal computed tomographic scanning showed enlarged lymph nodes in the para aortic region at the level of the right renal artery, which suggested metastasis of the carcinoma. Metastatic lymph node swellings probably caused compression of the right renal artery. PMID- 8480920 TI - A case report of siblings with hypertrophic cardiomyopathy that progressed to dilated cardiomyopathy--case reports. AB - The authors encountered 2 brothers with hypertrophic cardiomyopathy (HCM), both of whom were later found to have progressed to dilated cardiomyopathy (DCM). Case No. 1 (younger brother): A diagnosis of HCM without left ventricular (LV) dilatation was made at age two by cardiac catheterization and echocardiogram. However, he had been well until age thirteen when dyspnea developed. Echocardiograms showed LV wall thickening (septum 20 mm, and posterior 18 mm) and LV dilatation (left ventricular diastolic diameter [LVDd] 60 mm) accompanied by LV dysfunction (ejection fraction [EF] 18%). At autopsy, the heart weighed 875 g and showed LV dilatation with thickened walls. Case No. 2 (elder brother): At age twelve, he was found to have an increased heart size on x-ray when his family was evaluated owing to his brother's condition. Cardiac catheterization and echocardiogram showed HCM without LV dilatation. He remained asymptomatic until age twenty when dyspnea developed, at which echocardiography showed a dilated LV. The authors speculate that the HCM with progression to DCM is an atypical type of familial HCM and that progression to DCM is genetically determined. PMID- 8480921 TI - Giant congenital left ventricular aneurysm in an adult--a case report. AB - Congenital cardiac aneurysms are extremely rare. The echocardiographic features of this condition have never been described. The authors report a case of giant congenital left ventricular aneurysm wherein the diagnosis was made by echocardiography and confirmed at cardiac catheterization. The aneurysm was surgically removed. The histologic examination showed that the aneurysmal wall was only 1.5 to 2 mm thick but contained all the layers of the heart. PMID- 8480922 TI - Coronary artery ectasia--a case report and literature review. AB - A case report of coronary artery ectasia is presented. A middle-aged man was admitted with sudden onset of respiratory arrest which is a rather rare occurrence. Relevant articles are reviewed, and discussion mainly concerns the etiologic and pathophysiologic point of view. PMID- 8480923 TI - Indium 111-labeled platelets accumulation over abdominal aortic graft with chronic disseminated intravascular coagulation--a case history. AB - The authors describe a seventy-six-year-old man with aortic graft, which became the focus of chronic disseminated intravascular coagulation (DIC). The patient had abdominal aortic aneurysm (AAA) and the size had increased up to 38 mm in diameter. The AAA was excised and replaced by Dacron graft. Ten months later, the DIC became chronic with renal dysfunction. Indium 111-labeled platelets scintigraphy showed increased accumulation of radioactivity over the graft. In the treatment of chronic DIC, low-dose subcutaneous heparin injection (5,000 10,000/day) was effective, and he was discharged. In this case there was also suspicion of lung cancer and recurrent aortic aneurysm, which were a more reasonable cause of chronic DIC. This case suggests that an aortic graft prosthesis may be a cause of localized chronic DIC and that indium 111-labeled platelets scintigraphy is useful for the detection of localized chronic DIC. Moreover, subcutaneous heparin administration may be effective for chronic DIC in patients with an abdominal aortic graft prosthesis. PMID- 8480924 TI - From Peachtree Street and back. PMID- 8480925 TI - Laparoscopic inguinal herniorrhaphy in a swine model. Third place winner of the Conrad Jobst Award in the Gold Medal paper competition. AB - A simplified method of laparoscopic inguinal herniorrhaphy using prosthetic materials was evaluated in a swine hernia model. The goals of this study were to determine 1) effectiveness of repair in a rapidly growing animal, 2) effectiveness and extent of adhesion formation of different prosthetic materials, 3) the effect of repair on testicular growth, and 4) histologic effects on the hernia site and surrounding structures. In a prospective randomized study, 30 juvenile male swine (average, 23 kg) with 35 congenital indirect inguinal hernias underwent laparoscopic herniorrhaphy using one of three prosthetic materials: Group 1 (polytetrafluoroethylene/Gore-Tex), N = 10; Group 2 (polypropylene mesh/Marlex), N = 10; Group 3 (polypropylene mesh/Prolene), N = 10. A standardized laparoscopic herniorrhaphy technique consisting of stapling prosthetic material over the hernia defect without peritoneal dissection was employed. During the 3-month postoperative period, animals were sequentially examined for normal growth and development, normal testicular development, and signs of hernia recurrence. Clinically apparent complications related to herniorrhaphy occurred in five animals (17%) during the observation period (one with repair failure, one with testicular torsion, two with repair failure and bowel obstruction, and one with intestinal obstruction secondary to adhesions). All three animals with bowel obstruction died. At 90 days after surgery all remaining animals (N = 27) were euthanized (Group 1 = 9, Group 2 = 8, Group 3 = 10). Average weight was 84 kg. Necropsy findings included no additional hernia recurrences, and one mesh erosion into the urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480926 TI - Elective procedure for peptic ulcer: a disappearing operation. AB - We retrospectively reviewed all the operative procedures performed for benign peptic ulcer disease in a regional hospital during the past 6 years. The indications were hemorrhage, perforation, obstruction, chronicity, and gastrocolic. No operation for chronicity has been performed since 1986. Only in perforation was there a statistical difference between male and female. Two hundred forty-six patients were admitted for bleeding, 108 were given transfusions and 38 required operative intervention for control of bleeding. The average units of blood given to patients with bleeding, who underwent operative intervention and recovered, was 7.2. The 6 deaths in this group were in patients who received 15.7 units of blood. Of these, none survived. Twenty patients with perforated ulcers were successfully treated with gastric resection with vagotomy. One patient with a perforated ulcer had primary suture repair, another had vagotomy and pylorplasty. Both required gastric resection because of obstruction and reperforation, respectively. Gastric resection with truncal vagotomy successfully corrected obstruction in 18 patients and chronicity in 9 patients, without mortality. Death from hemorrhage is directly related to delay in operative intervention. With the availability of effective medication for control of gastric acidity, the need for selective vagotomy or elective operative procedure for ulcers is fast disappearing. PMID- 8480927 TI - Safety, efficacy, cost, and morbidity of laparoscopic versus open cholecystectomy: a prospective analysis of 228 consecutive patients. AB - Laparoscopic cholecystectomy has become the procedure of choice in most hospitals for the resolution of surgically treatable gallbladder disease. Few reports address the results of laparoscopic cholecystectomy in comparison to open cholecystectomy during the same time interval within the same institution. One hundred ninety-six laparoscopic cholecystectomies were performed from April 1990 through February 1991. Initial patient selection was restricted to elective procedures for chronic cholecystitis with expanded indications as experience was gained. Of the 196 cases, 11 required conversion to open cholecystectomy, leaving 185 laparoscopic cholecystectomies for comparison. During the same period, 82 open cholecystectomies were performed. Thirty-nine of these were complicated cases and would not have been considered for laparoscopic cholecystectomy early in the study, leaving 43 routine open cholecystectomies for comparative purposes. In the laparoscopic group, 1.1 per cent of the patients had major operative complications as opposed to the open group, which had none. There were no common bile duct injuries in either group. To provide a true cost-benefit analysis, a group of patients was identified that would qualify for elective, same-day admission for either an open or laparoscopic procedure. Laparoscopic cholecystectomy (LC) was performed on 70 patients, and open cholecystectomy (OC) was performed on 26 patients. A comparison of data from these groups showed no significant difference in age or sex. Hospitalization costs averaged $5,390 for the LC group versus $5,392 for the OC group. Postoperative hospital stay averaged 1.3 days for the LC group versus 3.7 days for the OC group (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480928 TI - Impact of a major hurricane on surgical services in a university hospital. AB - Hurricane Hugo struck Charleston, South Carolina, on September 21, 1989. This report analyzes the impact this storm had upon surgical care at a university medical center. Although disaster planning began on September 17, hurricane damage by high winds and an 8.7-foot tidal surge led to loss of emergency power and water. Consequently, system failures occurred in air conditioning, vacuum suction, steam and ethylene oxide sterilization, plumbing, central paging, lighting, and refrigeration. The following surgical support services were affected. In the blood bank, lack of refrigeration meant no platelet packs for 2 days. In radiology, loss of electrical power damaged CT/MRI scanners and flooding ruined patient files, resulting in lost information. In the intensive care unit, loss of electricity meant no monitors and hand ventilation was used for 4 hours. In the operating room, lack of temperature and humidity control (steam, water, and suction supply) halted elective surgery until October 2. Ground and air transportation were limited by unsafe landing sites, impassable roads, and personnel exhaustion. Surgical planning for a major hurricane should include: 1) a fail-safe source of electrical power, 2) evacuation of as many critically ill patients as possible before the storm, 3) cancellation of all elective surgery, and 4) augmented ancillary service staffing with some, although limited, physician support. PMID- 8480929 TI - Injury severity dictates individualized antibiotic therapy in penetrating abdominal trauma. AB - Antibiotics play a crucial role in reducing the risk of postoperative infection in patients suffering penetrating abdominal trauma. The infection rate for patients with these injuries ranges from 7% to 16%. Single agents with broad spectrum activity have proven efficacy, but dosage and duration are still controversial. A prospective, double-blinded study was performed on 102 patients randomized to receive one of three antibiotics for a total of 12 hours: cefoxitin (3 doses, 31 patients); ceftizoxime (2 doses, 36 patients); or mezlocillin (3 doses, 35 patients). Two distinct groups at risk for postoperative infection were evident depending on the severity of injury: Group A were those with no colon injury or a colon injury that could be repaired, no evidence of shock, or fewer than 3 organs injured; Group B were those requiring a colostomy, evidence of shock on presentation, or three or more organs injured. All comparisons of the patient populations receiving the different antibiotics showed the two groups to be equivalent. The mean penetrating abdominal trauma index for Group A was 8.8 and 28.2 for Group B. The overall infection rate for Group A was 10.3% and 42.3% for Group B. There was a significant increase in infection rate for all antibiotics except ceftizoxime in Group B compared with group A. The penetrating abdominal trauma index was significantly higher in all patients who developed infection for all antibiotics. In addition, if the surgical wound was closed primarily, patients with colon injuries developed wound infections 71% of the time, and those with small-bowel injuries did so 30% of the time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480930 TI - Management of epiphrenic esophageal diverticula. A fifteen-year experience. AB - Epiphrenic esophageal diverticula represent an unusual cause of dysphagia, pain, and weight loss. Although commonly associated with motility disorders, distal esophageal diverticula also have been associated with reflux strictures or other lesions. To determine the most appropriate diagnostic evaluation and operative approach, we reviewed the recent 15-year experience with epiphrenic esophageal diverticula at our institution. Over the study period, 18 patients were diagnosed with pulsion epiphrenic diverticula. Nine patients (50%) with symptomatic diverticula were referred for surgical management. All referred patients were evaluated with preoperative manometry, endoscopy, and contrast esophagography. Diverticulectomy was performed via posterolateral thoracotomy in all patients, combined with myotomy in the 6 patients (67%) with abnormal manometric results and in 2 patients with normal manometric results. The third patient with normal manometric results underwent simple diverticulectomy. There was no operative mortality. One complication, a small esophageal leak, was managed successfully by early reoperation. All patients were free of dysphagia at discharge. Follow-up was obtained for 17 patients (94%) ranging from 3 months to 12 years. Good to excellent results (measured by relief of symptoms, weight gain, and absence of clinical recurrence) were seen in all 9 surgical patients; 6 of 9 nonsurgical patients remained or became symptomatic. This experience demonstrates the efficacy of surgical management of symptomatic epiphrenic esophageal diverticula. Diverticulectomy combined with selective myotomy permits excellent operative results and resolution of associated symptoms. PMID- 8480931 TI - Definitive treatment of colon injuries: a prospective study. AB - The results of a prospective protocol for penetrating injuries of the colon in 252 patients are presented. The protocol emphasized definitive management of the injury by repair, resection and anastomosis or exteriorized repair. Colostomy was reserved for left colon injuries requiring resection or for delayed treatment. Two hundred nineteen patients (86.9%) had definitive treatment by repair (N = 159), resection and anastomosis (N = 26), or exteriorized repair. This was successful in 205 patients (93.6%). Three patients had anastomotic leak after repair or ileocolostomy. Eight of the 34 patients with exteriorized repair had suture-line breakdown and 26 (76.5%) patients avoided a colostomy. Injury severity indices (anatomic: Abdominal Trauma Index and Flint grading of colon injury) were higher in the exteriorized repair than in the repair group. Postoperative abdominal abscesses occurred in 43 patients (17.1%). A multiple regression analysis identified the Abdominal Trauma Index (P < 0.0001) and the presence of colostomy (P < 0.0004) as significant independent factors in association with this complication. Mortality from sepsis was 2.4 per cent (6 patients) and in only one patient was the death directly related to colon injury management. We conclude that the majority of colon injuries can be managed by repair or resection with anastomosis. End colostomy is unavoidable in Flint 3 injuries of the left colon. In other situations, ileocolic or colocolic anastomoses appear to be safe in hemodynamically stable patients. Loop colostomy has a role in delayed treatment, but can be replaced by an exteriorized repair in Grade 2 colon injuries that do not require resection. PMID- 8480932 TI - Systemic and mesenteric vascular effects of platelet-activating factor and cocaine. In vivo effects on a neonatal swine model. AB - Mesenteric hypoperfusion may be responsible for alterations in gut mucosa leading to necrotizing enterocolitis. Platelet-activating factor (PAF) and cocaine have been implicated in the etiology of necrotizing enterocolitis. We have demonstrated direct toxic effects of these compounds in vitro, but the in vivo mechanism of bowel damage is unknown. Newborn piglets (3.0 +/- 0.3 kg) had physiologic parameters (electrocardiogram, blood pressure, pulse, and central venous pressure) continuously monitored as well as Doppler probe recordings of superior mesenteric artery flow (Qsma). Aortic flow with calculation of cardiac index, and systemic and mesenteric vascular resistances (SVR and MVR) were also determined. Group 1 (N = 8) received PAF (0.5 microgram/kg). Groups 2 (N = 8) and 3 (N = 8) received high (17 mg/kg) and low (9 mg/kg) doses of cocaine, respectively. Each subject served as its own control. Histology demonstrated edema or early mucosal hemorrhage in all groups. PAF caused a third-degree atrioventricular block of short duration and a prolonged decrease of the cardiac index, but only a brief elevation of SVR and MVR. The cocaine groups had a sustained increase of SVR and MVR associated with a decrease of cardiac index. The decrease of Qsma paralleled the changes of MVR in each subject. These data show that both PAF and cocaine induce mesenteric ischemia. The effect of PAF is of short duration and mainly related to its cardiotoxic effects resulting in low Qsma. Cocaine causes an increase in MVR with prolonged depression of mesenteric flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480933 TI - Natural history and clinical evaluation of the lumpectomy scar. AB - After lumpectomy with axillary dissection and radiation therapy, there are numerous changes that occur to the breast that, if unrecognized as routine, post treatment changes, can lead to inappropriate intervention by the physician. The purpose of this study is to evaluate the time required to achieve stable post treatment mammographic and physical findings. One hundred twenty-three patients age 56.6 years with a mean tumor size of 15.9 +/- 8.2 mm were observed every 6 months with a mean change in scar size of 16.7 +/- 10.6 mm. A scar never developed in 27 per cent and completely resolved or decreased in 90 per cent. Calcifications developed in 16 per cent of the patients; 40 per cent in the scar, 60 per cent outside the scar. Recurrence developed in 2 per cent of the patients at a mean time of 53 months and was believed to be favorably influenced by cytologic evaluation of the resection margins at the time of tumor excision. Stabilization or resolution of the post-treatment changes occurred within 24 to 36 months. The conclusion is for careful surgical and radiologic follow-up with examinations, fine-needle aspirations, and meticulous mammograms guiding the need for biopsy. PMID- 8480934 TI - Sepsis and infection in the intensive care unit: are they related? AB - Sepsis is a clinical syndrome characterized by fever, leukocytosis or leukopenia, tachycardia, increased cardiac index, reduced systemic vascular resistance, and hypercatabolism. It is generally believed to be a response to invasive infections, although an infectious source cannot always be identified in patients with sepsis. Over an 18-month period 287 patients were admitted for more than 48 hours to a noncardiac adult surgical intensive care unit. Data were collected concurrently and recorded in a computer database. Seventy-three patients (25%) developed sepsis, and 50 (68% of those with sepsis) had bacteremia, with a mean of 1.5 organisms and 3.5 positive blood cultures per patient. Only 22 of 50 patients with bacteremia had a potential infectious source, and there was a concordance of cultures from the putative source and the blood stream in only 10 patients. Forty-one patients with sepsis (56%) had no apparent infectious source, but 28 of these (68%) had bacteremia, often with multiple organisms. Forty of the 73 patients with sepsis died in the hospital. Mortality in sepsis could not be predicted by the presence of an infectious source (P > 0.35) and was not related to bacteremia (P > 0.75). Mortality was strongly associated with the development of multiple organ failure (P < 0.0001). Sepsis is a generic response to a number of physiologic insults and does not require infection for expression. This inflammatory response may have survival value by increasing oxygen delivery to sites of injury, but uncontrolled inflammation may cause dysfunction in several vital organ systems. The associated immunosuppression results in bacterial colonization of sites from which bacteria ordinarily are excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480935 TI - Decreased red blood cell deformability and impaired oxygen utilization during human sepsis. AB - Sepsis is characterized by decreased microcirculatory flow and increased peripheral shunting. Previous studies have shown red blood cell deformability (RCD) is decreased during sepsis. The purpose of this study was to evaluate the effect of changes in RCD on hemodynamics and oxygen utilization during sepsis. RCD, arteriovenous oxygen difference (DA-VO2), mixed venous oxygen saturation (MVO2), intrapulmonary shunt (QS/QT), cardiac index, and systemic vascular resistance were measured in 10 trauma patients, all of whom had or developed clinical sepsis. Data are expressed as mean +/- SD. Patients with normal RCD (> 0.75) were compared with those with low RCD (< 0.75). Patients with low RCD had a significantly higher incidence of sepsis (100% vs. 20%, P < 0.05, Student's t test or Fisher's Exact Test), lower DA-VO2 (2.4 +/- 0.9 vs. 4.8 +/- 1.5 P < 0.05, Student's t test or Fisher's Exact Test), and higher MVO2 (79 +/- 8 vs. 65 +/- 11 P < 0.05, Student's t test) or Fisher's Exact Test) than those patients with normal RCD. There was a direct correlation between RCD and DA-VO2 (r = 0.852, P < 0.001). MVO2 correlated inversely with changes in RCD (r = 0.813, P < 0.001). No significant correlation existed between RCD and cardiac index or systemic vascular resistance. Patients with low RCD demonstrated impaired oxygen utilization; changes in RCD correlated closely with changes in DA-VO2 and MVO2. These data suggest that decreased RCD may have an etiologic role in the impaired oxygen utilization that occurs during sepsis. PMID- 8480936 TI - Role of the leukocyte in endotoxin-induced alterations of the red cell membrane. Second place winner of the Conrad Jobst Award in the Gold Medal paper competition. AB - Sepsis and endotoxemia are known to be associated with alterations in the red cell membrane that result in diminished flexibility. This decreased flexibility may be responsible, in part, for the microcirculatory abnormalities accompanying sepsis. The etiology of these sepsis-associated changes remains unclear. This study evaluates the role of the white blood cell in these abnormalities. Specimens were obtained from 44 volunteers and divided into two treatment groups. Group I specimens were incubated with Escherichia coli endotoxin (2 micrograms/ml) followed by removal of the white blood cells. The white blood cells were removed from group II specimens before endotoxin incubation. Paired, saline-incubated samples served as controls. After incubation, washed erythrocytes were evaluated for deformability and membrane viscosity. Deformability was assessed by filtration through 4.7-microns membranes. Red cell deformability was expressed as filtration rate (volume of cells per second per square centimeter). Membrane viscosity was assessed by fluorescent spectroscopy of cells into which the membrane probe 1(4-(trimethylamino)-phenyl)-6-phenyl 1,3,5-hexatriene had been incorporated. Results were expressed as anisotropy. Endotoxin resulted in a significant increase in erythrocyte membrane viscosity (experimental, 0.296 +/- 0.002 vs. control, 0.284 +/- 0.002, P < 0.001). This was reflected by a significant decrease in cellular deformability (experimental, 142.55 +/- 6.55 vs. control, 157.86 +/- 8.63, P < 0.01). However, these alterations are not a direct effect of endotoxin, but require the presence and participation of the white blood cell and/or its mediators (experimental, 0.301 +/- 0.002 vs. control, 0.300 +/- 0.001, P = NS). PMID- 8480937 TI - [Food allergy: nutritional value and allergenic properties of hypoallergenic formulas]. PMID- 8480938 TI - [Use of the thermometer among mothers of young children]. AB - Due to the importance of fever and its correct measurement, we try to describe in our study the use of the thermometer by a sample of mothers of young children chosen at random in a low-middle class neighborhood. We surveyed them at home and checked their use of the thermometer. We found a frequent and correct usage of the thermometer. We identify the mother's educational level as one indicator of some of the mistakes in their use of the thermometer. We propose specific points to teach every mother when she goes to the pediatrician in order to provide adequate use of the thermometer in children with fever. PMID- 8480939 TI - [Percutaneous balloon valvotomy in neonatal obstructive cardiopathy. I: critical pulmonary valvular stenosis]. AB - Percutaneous pulmonary balloon valvotomy using one balloon or more in sequential approach was attempted in 9 no selected neonates with critical pulmonary valve stenosis between March 1985 and October 1990 (mean age 10 + 8.6 days). The procedure was successful in seven of them (78%) in whom with a 1.22 + 0.2 balloon/annulus ratio the right ventricular systolic pressure decreased from 96 to 45 mmHg (p < 0.001), the transvalvular gradient from 65 to 23 mmHg (p < 0.001); and the systemic oxygen saturation increased from 69 to 86% (p < 0.001). In one patient the valve was not crossed. Two patients underwent surgery because unsuccessful balloon valvotomy result in the immediate and mid term period: hypoplastic right ventricle in one, and inferior vena cava thrombosis that prevent a second dilation in the other respectively. The mid term follow up showed a 62% (5/8) of successful result. Although the complex methodology and complications are not uncommon, the balloon pulmonary valvotomy is a safely and effective therapy for neonates with critical pulmonary stenosis. PMID- 8480940 TI - [Isolation of Ureaplasma urealyticum in respiratory samples from two patients with bronchiolitis]. AB - We report the cases of two patients, 5 and 4 months of age, without clinically important antecedents, that were hospitalized with a bronchiolitis syndrome. In the respiratory samples (nasopharynx aspirates) of both patients we isolated Ureaplasma urealyticum in pure culture and with a quantitative count > 10(3) cfu/ml. Vaginal cultures of mothers were negative. The patients were treated with fluid therapy and salbutamol, and after the respiratory cultures were reported positive, with erythromycin for 7 days. Because of the age of the patients (not in the neonatal period) and the type of respiratory syndrome (bronchiolitis), it is very difficult to evaluate the real clinical significance of these isolations. We review the respiratory pathology caused by U. urealyticum during the neonatal period and we recommend the need for a multicenter study about the clinical significance of this microorganism in children under one year of age. PMID- 8480941 TI - [Fibrin adhesive: a new therapeutic alternative in the treatment of cystic lymphangioma]. AB - We present three cases of cystic lymphangioma of the neck, treated with a new therapeutic method which consists of an injection of fibrin adhesive into the lesion following aspiration of the liquid contents of the lymphangioma. Two of the cases had been treated surgically and were faced with the recurrence of the tumor, the aforesaid treatment was applied. In the third case, it was the only therapy applied. We believe that the results obtained were excellent in all three cases. PMID- 8480942 TI - [A study from Navarra. Hyperlipidemias. Avarage scores and percentiles for lipids and lipoproteins in a population of children and adolescents. Correlation with anthropometric parameters]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, the following parameters: total cholesterol, HDL cholesterol, LDL-cholesterol, triglycerides and C/HDL and LDL/HDL risk quotients were determined in 5,829 children. These children, of both sexes and between the ages of 4 and 17 years, were selected at random from the school population in our community. Average values and percentiles of these parameters were obtained for each group according to age and sex as a previous step to define the health condition or "lipid risk" in our population. When determining the correlation of these biochemical parameters with the anthropometrical parameters of BP, age, weight, height, Quetelet Index, body mass surface, skinfold thickness and the percentage of subcutaneous fat (after the necessary logarithmic transformations, adjusted to each age and sex group by Z-scores) we find that none of the correlation coefficients are significant. The triglycerides and the HDL cholesterol have a low, but significant. The triglycerides and the HDL cholesterol have a low, but significantly, correlation with the other lipid parameters. The lipid risk quotient (C/HDL, LDL/HDL) shows a higher correlation with LDL-cholesterol than with total cholesterol. PMID- 8480943 TI - [A study from Navarra. Hyperlipidemia V. What is the best definition of hyperlipemia in childhood and adolescence?]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analyzed in 5,829 children of both sexes, between 4-17 years of age, and selected at random from the school population in our community. In this article, we analyze the different definitions for lipid risk during childhood, whether based on percentile values, according to age and sex of the child, of cholesterol, LDL/cholesterol, or risk quotients (C/HDL, LDL/HDL), or even on the absolute values of all of these parameters. An appropriate definition for hyperlipemia during childhood, once we know the average variations in the levels of lipids and lipoproteins according to age and sex, as well as the variations of the lipid risk prevalence according to its definition, would be: 1. Previous screening according to cholesterol serum levels: Values higher than the 70th percentile for each group according to age and sex: or higher than 185 mg/dl for children age 4 to 12 and 170 mg/dl for children age 13 to 17. 2. To calculate the LDL/HDL quotient among those selected children included in the definition of hyperlipemia when the quotient is higher than the 85th percentile for the patients age and sex, or it is higher than 2.2. PMID- 8480944 TI - [Prognosis of perinatal asphyxia in full-term neonates]. AB - We have performed a prospective study in 65 asphyxiated term newborns to evaluate the prognostic value of three different methods: 1) Neurological examination, 2) Electroencephalographic tracings (EEGs) and 3) Transfontanellar sonography, carried out periodically from birth until discharged from the neonatal unit. The neurological status of surviving infants was assessed at one year of age. We found a statistically significant (p < 0.0001) association between the neurological examination, electroencephalographic tracings and transfontanellar sonography during the neonatal period and the neurological development. The prognostic value, as a function of sensibility, specificity and predictive value of the three methods was very high. No differences were found among them, although the EEGs and neurological examinations showed the highest predictive values. PMID- 8480945 TI - [Increased serum levels of soluble IL-2 receptor in food intolerance: possible mechanism of delayed immunity in milk intolerance]. AB - The levels of soluble interleukin-2 receptor (sIL-2R) were measured in 35 serum samples from children with food intolerance; 19 had an IgE-mediated sensitization and were considered as atopic patients, skin tests and RAST were negative in the remaining 16 children and they were diagnosed as having cow milk intolerance (CMI) Forty-three coeliac patients were included as a positive control group and 18 normal children as the negative control group. The atopic group showed normal values of sIL-2R (1,183 +/- 468 u/ml); however, it was increased in children with CMI (1,453 +/- 469 u/ml, p < 0.05). The sIL-2R mean value was highest in patients with gastrointestinal symptoms (1,458 +/- 461 u/ml, p: 0.03) and the presence of atopic dermatitis was not relevant. The sIL-2R was also elevated in 8 children with igE-mediated sensitization against cow's milk (1,477 +/- 328 u/ml, p < 0.05). These results suggest that a delayed cellular mechanism occurred in CMI, similar to that present in coeliac disease, although it was less severe. In addition, there is an overlap of humoral and cellular immunological mechanisms in the IgE-mediated sensitization to cow's milk, but we did not find this coincidence in the allergy to remaining foods. From a pathogenic point of view, to separate CMI from IgE-mediated allergies to milk does not seem to be sufficiently justified at the present time. It is possible that the atopy against cow milk proteins in children has a different immunological mechanism than the atopy to other foods, which would explain its better prognosis. PMID- 8480946 TI - [The role of calcium ions and temperature on the effect of exogenous semisynthetic surfactants (experimental study)]. AB - With the final aim of preventing neonatal respiratory distress syndrome (RDS), the present study was carried out on premature rabbits (28 days of gestation) that showed a moderate level of RDS. These animals were treated intratracheally with 25 microliters of semisynthetic surfactant, composed of natural adult rabbit surfactant/DPC/DPPG (1/0.6/0.6 mol P) in two types of carriers, saline solution (Sf) and a calcium solution (5 mM of Cl2Ca), which were also used as controls. This was maintained throughout the experimental period at 37 degrees C or 60 degrees C, while checking the effect of temperature on their behavior. The final results in the P/V curves showed a significant increase in the maximum distention in the cases treated with semisynthetic surfactant at 60 degrees C with calcium vehicle (60.96 ml/kg) and with saline solution as the vehicle (58.51 ml/kg) with respect to the control without treatment (44.08 ml/kg) (p < 0.05). In the morphometric quantification of the lungs fixed to 10 cm H2O, the highest distention (VV) is reached by the semisynthetic surfactant in calcium solution (Mez.Ca) at 37 degrees C (56.30%) and 60 degrees C (56.31%), followed by the semisynthetic surfactant in saline solution at 37 degrees C (55.17%). The maximum compliance expressed the highest distention (with or without emphysema) and the morphometric distention together with the compliance at 10 cm H2O showed the residual trapping and/or anticollapsing effect. The temperature and the type of vehicle used for the semisynthetic mixture did not significantly influence the lung distention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480947 TI - [Glutaric aciduria type I]. AB - We report three patients with glutaric aciduria type I. The biochemical diagnosis of two cases was revealed by determination of free glutaric acid in urine, by using the CG/EM method. In the third patient, however, these levels were only slightly increased and the diagnosis was attained by the determination of total glutaric acid and glutaryl-carnitine. Serum carnitine levels were decreased in two cases. Clinical symptoms of this type of organic acidemia are highlighted by an acute or subacute presentation with signs of dysfunction of the neostriatum, simulating a cerebral paralysis with extrapyramidal signs. Homozygous patients have been reported with the same biochemical and enzymatic activity findings, but these patients were neurologically asymptomatic throughout life. Other features suggestive of the disease are macrocephaly associated with a widening of the subarachnoid spaces. Riboflavin and carnitine administration to these patients seems to prevent new bouts of neurological dysfunction. PMID- 8480948 TI - [Dystonia as a principal manifestation of Leigh syndrome in an infant]. PMID- 8480949 TI - [Virilizing adrenal carcinoma: exeresis and successful treatment with op'DDD]. PMID- 8480950 TI - [Endotracheal and endobronchial tuberculosis. Variability of its clinical manifestation, diagnostic and therapeutic importance of flexible endoscopy]. PMID- 8480951 TI - [Aspergillus infection of the vascular prosthesis in a child with aortic coarctation. Evolution and therapy]. PMID- 8480952 TI - [Epidemiology of bites in a child day-care center]. PMID- 8480953 TI - [Benign myoclonus in infancy]. PMID- 8480954 TI - [Transient hyperphosphatasemia in childhood: 2 new cases at an unusual age]. PMID- 8480955 TI - [Apropos of a case of multiple deprivations: difficulty of evaluation and psychosocial intervention in childhood]. PMID- 8480956 TI - Management of hypertension after ambulatory blood pressure monitoring. AB - OBJECTIVE: To study the test-ordering behavior of practicing physicians regarding ambulatory monitoring of blood pressure and to assess changes in patient management after this study. DESIGN: Cross-sectional assessment of physicians' practice habits regarding the ordering of ambulatory blood pressure monitoring and a longitudinal study of patient management after monitoring. SETTING: Physicians' offices in central Connecticut. PARTICIPANTS: Two hundred thirty seven consecutive patients referred by 65 community- and hospital-based physicians. MEASUREMENTS: Indications for ambulatory blood pressure monitoring, changes in diagnosis and therapy, and office blood pressures before and after the ambulatory blood pressure study. RESULTS: The main indications for ordering the test included borderline hypertension (27% of studies ordered), assessment of blood pressure control during drug therapy (25%), evaluation for "white coat" or "office" hypertension (22%), and drug-resistant hypertension (16%). After the ambulatory blood pressure study, only 13% of the patients had further testing (for example, echocardiography); the diagnosis was changed in 41% of the patients, and antihypertensive therapy was changed in 46%. In 122 patients for whom data were complete, office blood pressure measured by the referring physician decreased from 161/96 +/- 22/12 mm Hg before the ambulatory blood pressure study to 151/86 +/- 27/12 mm Hg 3 months after the study (P = 0.004 for systolic blood pressure and P < 0.001 for diastolic blood pressure). One to 2 years after the study, office blood pressure was 149/86 +/- 24/12 mm Hg (P > 0.2 compared with 3 months after the study). Seventy-two percent of the patients had a lower office blood pressure within 3 months of the ambulatory blood pressure study. CONCLUSIONS: Practicing physicians use ambulatory blood pressure recordings for appropriate indications, and data from the monitoring studies affected the management of patients with hypertension. PMID- 8480957 TI - The effectiveness of ovarian cancer screening. A decision analysis model. AB - OBJECTIVE: To estimate the effectiveness of ovarian cancer screening with CA 125 and transvaginal sonography. DESIGN: Decision analysis was used to examine the no screen compared with the screen strategy. SETTING: Estimates of cancer incidence, survival, and life expectancy were derived from population-based data and clinical series. SUBJECTS: A cohort of 40-year-old women of all races and residing in the United States. INTERVENTIONS: A one-time screening intervention. The criterion standard for diagnosis of ovarian cancer was evaluation with exploratory laparotomy. MAIN OUTCOME MEASURE: Average years of life expectancy gained by women in the screened group. RESULTS: Screening for ovarian cancer with a combination of CA 125 and transvaginal sonography increases the average life expectancy in the population by less than 1 day. CONCLUSIONS: Given the limited effect on overall life expectancy, it is unlikely that mass screening for ovarian cancer with CA 125 and transvaginal sonography would be an effective health policy. PMID- 8480958 TI - Clinical manifestations of trichomoniasis in men. AB - OBJECTIVE: To determine the prevalence and clinical manifestations of trichomoniasis among sexually active men. DESIGN: Survey of two groups of men attending a sexually transmitted disease clinic. Subjects had a comprehensive sexual history and clinical examination plus cultures for Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis. PARTICIPANTS: The study included 147 sexual partners of women with trichomoniasis and 300 subjects selected randomly from heterosexual men coming to the same clinic for evaluation of new problems. MAIN OUTCOME MEASURES: Isolation of T. vaginalis was compared with urogenital signs and symptoms. RESULTS: The prevalence of T. vaginalis was 33 of 147 (22% [95% CI, 16% to 29%]) among sexual contacts of women with trichomoniasis and 17 of 300 (6% [CI, 3% to 9%]) among heterosexual men attending the same clinic. Men with trichomoniasis alone were more likely to complain of urethral discharge (P < 0.01), to have discharge on examination (P < 0.03), and to have inflammatory cells in their urethral secretions (P < 0.01) than were men who did not have T. vaginalis, N. gonorrhoeae, or C. trachomatis. Trichomonas vaginalis remained associated with nongonococcal nonchlamydial urethritis (adjusted odds ratio 3.8; CI, 1.1 to 11.2) after adjustment for race, age, number of sex partners in the previous 6 months, exposure to a partner with trichomoniasis, and history of trichomoniasis, urethritis, or gonorrhea. CONCLUSIONS: Trichomoniasis was common among men at risk for sexually transmitted diseases and was associated with symptoms and signs of urethritis. PMID- 8480959 TI - Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia. AB - OBJECTIVE: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia. DESIGN: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks. SETTING: Ambulatory patients recruited by 362 participating centers throughout the United States. PATIENTS: Women (n = 3390) from the total cohort of 8245 volunteers. MEASUREMENTS: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study. RESULTS: Among women, lovastatin (20 to 80 mg/d) produced sustained (12- to 48 week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol/L (160 mg/dL), and 40% to 87% achieved the goal of 3.36 mmol/L (130 mg/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin. CONCLUSION: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women. PMID- 8480960 TI - Pleural effusions in hospitalized patients with AIDS. AB - OBJECTIVE: To determine the incidence, cause, and characteristics of pleural effusions in hospitalized patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective. PARTICIPANTS: A total of 222 patients with AIDS hospitalized between January 1986 and January 1992 at the Medical University of South Carolina hospitals. RESULTS: Pleural effusions occurred in 59 patients for an overall incidence of 27%. The mean age of the patients was 35 +/- 2 years (SE) and the male to female ratio was 5:1. The cause was infectious in 39 (66%) patients, noninfectious in 18 (31%), and unknown in 2 (3%). Pleural effusions were caused by bacterial pneumonia in 18 (31%) patients, Pneumocystis carinii pneumonia in 9 (15%), Mycobacterium tuberculosis in 5 (8%), septic embolism in 2 (3%), Nocardia asteroides in 2 (3%), cryptococcus neoformans in 2 (3%), and Mycobacterium arium intracellulare in 1 (2%). Among noninfectious causes (n = 18), hypoalbuminemia was the cause in 11 patients (19%), cardiac failure in 3 (5%), and atelectasis, Kaposi sarcoma, uremic pleurisy, and adult respiratory distress syndrome in 1 (2%) each. Patients with AIDS who had pleural effusions had significantly lower serum albumin levels and had lower CD4 counts than did those without pleural effusions (P < 0.001). CONCLUSIONS: Pleural effusions are common in hospitalized patients with AIDS. Bacterial pneumonia is the most common cause for pleural effusion in AIDS. Large effusions are associated with Kaposi sarcoma and tuberculosis. Hypoalbuminemia is a common cause of noninfectious pleural effusions. PMID- 8480961 TI - Clinical course after liver transplantation in patients with sarcoidosis. PMID- 8480962 TI - Nodular lymphangitis: a distinctive but often unrecognized syndrome. AB - PURPOSE: To describe nodular lymphangitis by reviewing the clinical and epidemiologic features of this disease with an emphasis on distinguishing specific etiologic agents. DATA SOURCES: English-language articles were identified through a MEDLINE search (1966 to September 1992) using sporotrichosis, lymphangitis, and sporotrichoid as key words; additional references were selected from the bibliographies of identified articles. In addition, three new patients with nodular lymphangitis are described. STUDY SELECTION: One hundred fifty articles were reviewed to determine details of the etiologic agents and clinical signs and symptoms of patients with nodular lymphangitis. DATA SYNTHESIS: Nodular lymphangitis develops most commonly after cutaneous inoculation with Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum, Leishmania braziliensis, and Francisella tularensis. The setting in which infection is acquired is useful in differentiating among the various organisms causing infection. Sporotrichosis and leishmaniasis can have longer incubation periods than do the other common causes of nodular lymphangitis. A painful ulcer at the site of the initial lesion suggests tularemia; frankly purulent drainage often accompanies infections with Francisella and Nocardia species. Ulcerated or suppurating lymphangitic nodules occur commonly with Nocardia infections. Patients with nodular lymphangitis who fail to respond to empiric treatment for sporotrichosis should be evaluated for other organisms with appropriate biopsies and cultures. CONCLUSIONS: Nodular lymphangitis has distinctive clinical signs and symptoms, most commonly due to infection with a limited number of organisms. A detailed history, accompanied by information obtained from skin biopsy specimens using appropriate stains and cultures, should allow specific, effective therapy for most of these infections. PMID- 8480963 TI - Automated ambulatory blood pressure devices and self-measured blood pressure monitoring devices: their role in the diagnosis and management of hypertension. American College of Physicians. PMID- 8480965 TI - A way out. PMID- 8480964 TI - Characteristics of primary care office systems as predictors of mammography utilization. AB - OBJECTIVE: To evaluate the association between primary care office systems and mammography utilization by women older than 50 years. DESIGN: Cross-sectional. SETTING: An independent-practice association health maintenance organization (HMO) in Massachusetts. PARTICIPANTS: One hundred thirty-two primary care practices, representing 321 physicians and 4378 women with at least 12 months of recent, continuous assignment to a practice participating in the HMO. MEASUREMENTS: Practice characteristics and procedures for mammography referral and follow-up were ascertained by interviews of office managers. For each practice, the proportion of women older than 50 years who received a mammogram during their most recent 12-month period of assignment to the practice was calculated. MAIN RESULTS: Forty-five percent of eligible women received a mammogram during their most recent year of assignment to an HMO practice. In a regression model, use of one particular urban mammography center, group practice, and low percentage of Medicaid patients in the practice were each associated with 9% to 12% higher mammography utilization; use of flowsheets and the scheduling of mammograms by the patients themselves were associated with 7% to 9% higher utilization. Smaller, nonsignificant increases were associated with the use of reminders to patients (5%) and the presence of only internists on staff (5%). The model accounted for 51% of the variation in mammography utilization among practices. CONCLUSIONS: Mammography utilization among women older than 50 years, in a population in which cost was not a barrier, was related to specific office characteristics. Features of the mammography center, the process for scheduling mammograms, the use of flowsheets to prompt physicians, and the use of reminders to patients are important. PMID- 8480966 TI - Deciding about screening. PMID- 8480967 TI - United we stand. PMID- 8480968 TI - Screening for renovascular hypertension. PMID- 8480969 TI - Color Doppler ultrasound and deep venous thrombosis. PMID- 8480970 TI - Color Doppler ultrasound and deep venous thrombosis. PMID- 8480971 TI - Drug interaction of terfenadine and carbamazepine. PMID- 8480972 TI - The medical malpractice system. PMID- 8480973 TI - The medical malpractice system. PMID- 8480974 TI - The medical malpractice system. PMID- 8480975 TI - The medical malpractice system. PMID- 8480976 TI - More on medical malpractice. PMID- 8480977 TI - More on medical malpractice. PMID- 8480978 TI - [Annulo--aortic ectasia. Prognosis and treatment]. AB - Nine cases of aneurysm of the ascending aorta responsible for aortic insufficiency were identified between 1975 and 1989. Seven of these fell within the context of Marfan's syndrome, while the other 2 were idiopathic. Aortic leak was found to be massive from the outset in 5 cases and progressively worsened in 2 other cases. Mean follow-up was 138 months. Five patients were treated surgically, with nil mortality. Three corrective procedures were used: aortic valve replacement only or in combination with an additional procedure concerning the aorta (3 cases), or composite graft using the Bentall technique as modified by Cabrol (2 cases). There were 2 late complications among the incomplete procedures (detachment of the valve graft, recurrence of aneurysm). The 4 patients who did not undergo surgery all died: twice of aortic dissection and as a result of myocardial dysfunction in the other 2 cases. These results confirm the potentially grave course of this condition and emphasise the usefulness of routine surgery. Mastery of surgical techniques now justifies the extension of the indications of prophylactic surgery to any aneurysm having reached 6 cm. The Bentall technique modified by Cabrol remains the treatment of choice. PMID- 8480979 TI - [Mid-term follow-up after transluminal coronary angioplasty. Clinical results, mortality, morbidity apropos of 500 consecutive procedures]. AB - The aim of this study was evaluation of mid-term results, with a mean follow-up of 23 months (range: 6 months to 6 years), in 449 patients undergoing 500 consecutive angioplasty procedures before 1989. All of these 449 patients underwent primary angioplasty, and not dilatation after restenosis. Data processing of information, based upon a questionnaire filled out by the patient's own cardiologist, enabled 100 per cent follow-up. In these patients with a mean age of 56 (range: 32-83), angioplasty was single in 93 per cent of cases. The indication was unstable angina (45%), following a myocardial infarction (44%) or, more rarely, stable angina (10%). The anterior interventricular was dilated more often than the right coronary and circumflex (56%, 31% and 22% respectively). The cardiac survival rate of 41 months was 94.3 per cent, 78 per cent of patients not having experienced any serious coronary events at the time of last available information. 65 (sixty five) per cent of patients were asymptomatic and the Thallium stress test was normal in 67 per cent of them. Angina recurred in 17 per cent of patients, twice as often in women (p < 0.02). 14 (fourteen) per cent had undergone a bypass procedure and 14 per cent had been redilated. Comparisons by the Kaplan-Meier method showed less good results after the age of 57: higher mortality (p < 0.01), more frequent recurrences of angina (p < 0.05), more frequent aorto-coronary bypasses (p < 0.001). Aorto-coronary bypasses were commoner after dilatation of the anterior interventricular (p < 0.005), after multiple dilatations (p < 0.03) or after unstable angina (p < 0.05). PMID- 8480980 TI - [Irreversible auriculo-ventricular block of viral origin]. AB - Transitory disturbances of atrioventricular conduction are an usual feature of the acute phase of viral myocarditis. In contrast, the onset of complete heart block is rarer. The authors report a case of permanent heart block of progressive onset in a context of infectious mononucleosis in a 29-year-old male, requiring fitting with a permanent pacemaker. A long term follow-up visit confirmed the irreversible nature of the conduction disturbance. PMID- 8480981 TI - [Myocardial infarction, late fibrinolysis and resolving cerebral embolism]. AB - The authors report a case of a cerebral embolism, with a rapidly resolving course, during late fibrinolysis using tissue plasminogen activator in a patient with a posterolateral myocardial infarction. A review of the literature is used as basis for considering the effects of fibrinolytic treatment on left intraventricular thrombi during the acute phase of myocardial infarction. The risk of systemic embolism during such treatment is stressed. PMID- 8480982 TI - [Successive decrease of left ventricular segmental kinetic disorders after transluminal coronary angioplasties in the same patient]. AB - The authors report the case of a patient developing two successive left ventricular kinetic abnormalities secondary to acute or chronic ischemia, and reversible after transluminal coronary angioplasty. The concept of myocardial hibernation is suggested as a possible mechanism. PMID- 8480983 TI - [Localized type 2 dissection unrecognized by transesophageal echography. Apropos of a case]. AB - The authors report a case of type 2 dissection, strictly confined to the terminal portion of the ascending aorta, not seen by transesophageal echocardiography because of the existence of a blind spot and responsible for a false negative. The role of TEE in the diagnostic approach to dissections is reviewed, as are its limitations, of which it is important to be aware because of the poor prognosis of pathology of this type. PMID- 8480984 TI - [Simultaneous prescription of digoxin and an anti-arrhythmia agent, is it dangerous?]. AB - Many anti-arrhythmic drugs modify the pharmacokinetics of digoxin and increase serum levels. This possibility is considered for the majority of main anti arrhythmics on the basis of a review of the literature. Quinidine, propafenone, flecainide, amiodarone and verapamil increase blood digoxin levels, sometimes to twice their baseline values. Suggested mechanisms involve above all a decrease in clearance of digoxin and changes in its volume of distribution. Reported accidents considered to be a direct consequence of these interactions are nevertheless rare in the literature, and the need for modifying dose and increased cardiological surveillance in the case of such a combination is essentially a question of precaution. Disopyramide, procainamide and mexiletine do not appear to have any reported effects on the pharmacokinetics of digoxin, their combined prescription never having had any effect on blood digoxin levels. PMID- 8480985 TI - [Ambulatory or single measurement of blood pressure: comparison in a controlled trial in patients with hypertension]. AB - Single measurement during a visit and the calculation of blood pressure pattern from an ambulatory record are different criteria for evaluation of the efficacy of antihypertensive treatment. Results obtained by these two methods were compared in a controlled trial. Acebutolol or enalapril were given double-blind to 17 patients with uncomplicated moderate essential hypertension. After a two week run-in period (with dummy treatment), patients were allocated at random into two parallel groups. They took acebutolol (400 mg) or enalapril (20 mg) as a single daily dose for 3 months. Ambulatory measurement of blood pressure for 24 hours (Spacelabs 5200 SPM) was carried out the day prior to final inclusion, and at the end of the first then the third month of active treatment. A single measurement of blood pressure took place at the same times. Safety/acceptability of treatment based upon clinical and laboratory parameters was good. At inclusion, single measurements showed that all patients had a diastolic blood pressure (DBP) over 95 mmHg. However, ambulatory BP was significantly lower in the enalapril group. With treatment, the fall in DBP by single measurement was significant only at the first month with enalapril and at the third month with acebutolol while the effects of both drugs were significant on ambulatory systolic blood pressure (SBP) and DBP by the first month. Ambulatory BP revealed a superior antihypertensive action of acebutolol on SBP at the third month but this was not shown by single BP measurements. These results confirm the specificity of trial protocols of antihypertensive drugs based upon ambulatory BP measurements. PMID- 8480986 TI - [Antihypertensive action, clinical and biological acceptability of perindopril: main results in 23,460 patients with mild to moderate hypertension treated for 6 months in general practice]. AB - Efficacy and acceptability of perindopril (Coversyl) in general practice were evaluated in 23,460 hypertensive patients (52.9% women) during an open six month trial. Patients had essential mild to moderate hypertension (94 mmHg < supine DBP < 115 mmHg) associated or not with obesity (34%), diabetes (12%), hypercholesterolemia (36%), smoking habits (24%). Mean hypertension duration was 6.5 years, 70 p. cent of patients were 50 to 69 years old and 12 p. cent 70 years old or more. Perindopril was started at 4 mg except in older and patients with renal insufficiency (2 mg). If supine DBP remained > 90 mmHg the dose was doubled up to 8 mg/day, then a thiazide diuretic was added. Monotherapy was held in 90 p. cent of cases all along the study, more than 8 over 10 times at 2 or 4 mg/day. Normalized patients (DBP < or = 90 mmHg) were 69.87 and 95 p. cent respectively at the first, third and sixth month. Mean supine SBP and DBP decrease were 27.3 and 18.0 mmHg. Antihypertensive activity was similar in patients taking psychotrope or non steroidal anti-inflammatory agents and in others, as well as in older (> or = 70 years), diabetics and obeses, however with a significantly more frequent bitherapy in these last three sub-groups. Cough, a well known side effect of ACEI led to withdrawal in only 2.6 p. cent of cases. Withdrawals for side-effect were more frequent in older patients (6.1%), in those taking psychotrope (5.3%) or non steroidal anti-inflammatory agents (6.0%) than in diabetics (4.1%) or the others (4.1%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8480987 TI - [Aneurysm of the interatrial septum. Contribution of transesophageal echography. Relation with systemic embolic complications]. AB - The aim of this study was to evaluate the contribution of transesophageal echocardiography to the diagnosis of aneurysms of the interatrial septum and to identify the role played by this condition in unexplained systemic embolic accidents. Thirty two aneurysms of the interatrial septum were discovered in a consecutive series of 751 transesophageal echocardiograms, i.e. an incidence of 4.2 per cent. The diagnosis was possible by transthoracic echocardiography in only 9 cases (28%). Search for a patent foramen ovale by a contrast test was positive in 87 per cent of cases of aneurysm of the interatrial septum as compared with 45 per cent for patients without an aneurysm (p < 0.01). In patients in whom transesophageal echocardiography was requested for etiological evaluation of an ischemic vascular accident of embolic origin (n = 191), an aneurysm of the interatrial septum was found in 8.3 per cent of cases. In patients with no history of a systemic embolic accident (n = 560), the incidence of septums of the interatrial septum was 2.8 per cent (p < 0.01). Furthermore, 50 per cent of patients with an aneurysm of the interatrial septum had a history of systemic embolism. Transesophageal echocardiography thus appears to be superior to transthoracic echocardiography in the positive diagnosis of aneurysms of the interatrial septum and our study is suggestive of their emboligenic nature. PMID- 8480988 TI - Myxozyma vanderwaltii sp. nov. (Candidaceae), a new yeast species isolated from a flower of Protea repens (L.) L. AB - Three strains of an undescribed species of the genus Myxozyma were recovered. The new species differs from other accepted species of the genus in its assimilation pattern of carbon sources, mol% G + C and low DNA-DNA homology. A description of the new species, Myxozyma vanderwaltii, and a key to the species accepted in the genus are given. PMID- 8480989 TI - Mycelial elongation and sporulation of two fungi on amended media in light or dark. AB - Botrytis allii and Collectotrichum dematium are onion pathogens which can infect in the field and cause decay in storage. Some phenolics can hinder development of these fungi, but the effect of cytokinins is not clear. Cytokinins (kinetin or 6 benzyladenine) or phenolics (caffeic or chlorogenic acids) were added to agar at concentrations of 0 to 10(-3) M. Cultures were continuously irradiated with fluorescent light or maintained in the dark for 6 days. On unamended media, final mycelial elongation was 45 or 17.8 mm and sporulation was 28 or 10.6 x 10(4) spores/ml for Botrytis and Colletotrichum, respectively. For Botrytis, mycelial elongation was slightly (5%) but significantly increased and sporulation increased by 21% by incubation on phenolics as compared to cytokinins. Mycelial extension of Colletotrichum was not affected by amendment. Sporulation of Colletotrichum on kinetin was 16 to 28% greater than on the other amendments. As amendments concentration increased elongation of mycelia of both fungi decreased. Sporulation of Botrytis increased by 60% as amendment concentration increased from 0 to 10(-5) M and then decreased 25% at 10(-3) M. As amendment concentration increased from 0 to 10(-3) M, sporulation of Colletotrichum increased by 45%. Incubation in light increased mycelial extension 3 to 17% for Botrytis and Colletotrichum respectively, and sporulation was increased approximately 78% for both fungi. These compounds do not appear to inhibit development of these Botrytis or Colletotrichum species in culture. PMID- 8480990 TI - The use of neural networks to aid in microorganism identification: a case study of Haemophilus species identification. AB - Neural networks were evaluated as a tool for identifying microorganisms. Data from a microorganism identification table were used to train a neural network. Based on the results of identification tests the neural network could correctly identify each Haemophilus species from a group of 13 Haemophilus species. PMID- 8480991 TI - Why it pays for bacteria to delete disused DNA and to maintain megaplasmids. AB - Genetic information for disused metabolic systems is easily lost. This can be understood on the basis of a mathematic model for the description of the growth of individual microbial cells. The essential features of the model are that the uptake of nutrients is proportional to the surface area of the cell and maintenance costs are proportional to the volume. This explains why disused genes are easily lost. Growth of the individual cell continues until DNA replication of the genome is completed. The consequence is that cells with a large genome size are bigger at the moment of cell division. This results in a less favourable surface to volume ratio, which has a negative influence on the population growth rate. This means that cells with a smaller genome size will have a selective advantage. In cells in which the total DNA is divided over several units which replicate simultaneously (e.g. a cell with more chromosomes or a cell with one chromosome and one or more megaplasmids) a high surface to volume ratio can be maintained. The great metabolic differences between phylogenetically strongly related bacteria are due to loss of genetic information for complex metabolic characters in order to maintain a small genome size and a favourable surface to volume ratio. PMID- 8480992 TI - The growth kinetics of B. subtilis. AB - There has been considerable discussion by Kubitschek and Cooper concerning the growth rate of cells of E. coli throughout the cell cycle. Consequently, it is relevant to test Kubitschek's linear model against the exponential model espoused by Cooper (and many others) with another organism and another technique. Burdett et al. measured, by electron microscopy and computer analysis of the microphotographs, the distribution of lengths of a population of cells of Bacillus subtilis grown in 0.4% succinate in a minimal medium. The data were fitted to the extended Collins-Richmond method of Kirkwood & Burdett which subdivided the cell cycle into several phases. I have taken their results and compared them with the linear and exponential growth models for the entire cell cycle after applying correction to the data for the shape of completed and forming poles; i.e., to put the data on a cell-volume basis instead of a cell length basis. Most of the correction involves no arbitrary assumptions. The conclusion is that global volume growth rate is nearly proportional to cell volume; i.e. growth of Bacillus subtilis is nearly exponential for almost every cell in the growing culture. PMID- 8480993 TI - Regulation of the expression of the Pseudomonas stutzeri recA gene. AB - With the aid of recA-lacZ fusion strains, the in vivo regulation of the Pseudomonas stutzeri recA gene has been studied. It is shown that expression of this gene can be induced with a variety of DNA damaging agents, as well as with agents that interfere with DNA replication. For this induction, the presence of an active RecA protein is essential. Sequence analysis of the promoter region of the P. stutzeri recA gene showed that its open reading frame is preceded by an SOS-box, suggesting a regulation of its expression, similar to the regulation of recA expression in Escherichia coli. PMID- 8480994 TI - Anaerobic fungi and their cellulolytic and xylanolytic enzymes. AB - Anaerobic fungi are the inhabitants of the digestive tract of herbivorous mammals, ruminants as well as non-ruminants. One of the major characteristics of all anaerobic fungi examined thus far, is their production and secretion of a range of polysaccharide-degrading enzymes, including cellulases, xylanases and glucoside-hydrolases. The cellulolytic enzymes of the anaerobic fungus Neocallimastix frontalis have been shown to possess a high activity. Therefore anaerobic fungi and/or their enzymes could be interesting for many biotechnological applications including saccharafication of lignocellulosic residues, production of polysaccharidehydrolysing enzymes. This review summarizes the present knowledge of anaerobic fungi with special emphasis on their cellulolytic and xylanolytic enzymes. Further, a comparison with aerobic fungi is made. PMID- 8480995 TI - Effect of bacterial lipopolysaccharide on the content of lipid peroxidation products in lungs and other organs of mice. AB - The influence of lipopolysaccharide from Escherichia coli (LPS, 17 mg/kg body weight) on the lipid peroxidation process in organs of mice was studied. The content of conjugated dienes (CD), lipid peroxides (LP), malondialdehyde (MDA) (all three lipid peroxidation by-products), peroxidase (PO) activity and wet-to dry weight ratio in lungs, heart, spleen, kidneys and liver were determined 1.5 h after intravenous injection of LPS. Animals observed at this time-point had reduced activity and decreased body temperature by about 2 degrees C, however, all analysed organs did not reveal any changes of wet-to-dry weight ratio comparing to organs from mice injected with sterile, pyrogen free 0.9% NaCl. Only extracts from heart and lungs showed significant increase in the tissue level of at least two lipid peroxidation products. The heart content of CD, MDA, and LP was about 1.5-, 1.3-, and 2.4-fold higher than in control group. In lungs CD and MDA increased 3.3- and 1.3-times but in spleen only content of LP was elevated. In these organs the suppression of PO activity was also observed. Liver and kidneys did not reveal any convincing enhancement of lipid peroxidation process and alterations of PO activity. Since free radical reactions are involved in lipid peroxidation process and inactivation of PO these results suggest that heart, lungs and spleen are the organs mostly exposed to oxidative stress during the first 1.5 h after single injection of LPS in mice. PMID- 8480996 TI - Biosynthesis and function of trehalose in Ectothiorhodospira halochloris. AB - Trehalose 6-phosphate synthase, catalyzing the reaction between UDP-glucose and glucose 6-phosphate and forming trehalose 6-phosphate, was isolated and partially purified (30-fold) from the phototrophic, halo-alkaliphilic bacterium Ectothiorhodospira halochloris. The activity is stabilized by 20 mM MgCl2, 50 mM NaCe and 2M glycine betaine. The molecular weight was 63000. The enriched enzyme had a MgCl2 optimum at 3-6mM, a pH optimum at 7.5 (in Tris-HCl buffer) and a temperature optimum at 50 degrees C. The Km-values were 1.5 x 10(-3) M for UDP glucose and 2 x 10(-3) M for glucose 6-phosphate. The enzyme showed a salinity dependence with optimal concentrations between 100 and 300mM salt. Higher concentrations of salt resulted in a decrease in activity. In the presence of inhibitory salt concentrations the compatible solute glycine betaine had a protective effect with a maximum between 0.5 and 2.0M. PMID- 8480997 TI - In vivo labeling of Escherichia coli cell envelope proteins with N hydroxysuccinimide esters of biotin. AB - The primary amine coupling reagents succinimidyl-6-biotinamido-hexanoate (NHS-A biotin) and sulfosuccinimidyl-6-biotinamido-hexanoate (NHS-LC-biotin) were tested for their ability to selectively label Escherichia coli cell envelope proteins in vivo. Probe localization was determined by examining membrane, periplasmic, and cytosolic protein fractions. Both hydrophobic NHS-A-biotin and hydrophilic NHS-LC biotin were shown to preferentially label outer membrane, periplasmic, and inner membrane proteins. NHS-A- and NHS-LC-biotin were also shown to label a specific inner membrane marker protein (Tet-LacZ). Both probes, however, failed to label a cytosolic marker (the omega fragment of beta-galactosidase). The labeling procedure was also used to label E. coli cells grown in low-salt Luria broth medium supplemented with 0, 10, and 20% sucrose. Outer membrane protein A (OmpA) and OmpC were labeled by both NHS-A- and NHS-LC-biotin at all three sucrose concentrations. In contrast, OmpF was labeled by NHS-A-biotin but not by NHS-LC biotin in media containing 0 and 10% sucrose. OmpF was not labeled by either NHS A- or NHS-LC-biotin in E. coli cells grown in medium containing 20% sucrose. Coomassie-stained gels, however, revealed similar quantities of OmpF in E. coli cells grown at all three sucrose concentrations. These data indicate that there was a change in outer membrane structure due to increased osmolarity, which limits accessibility of NHS-A-biotin to OmpF. PMID- 8480998 TI - Distribution of viral abundance in the reef environment of Key Largo, Florida. AB - The distribution of viral and microbial abundance in the Key Largo, Fla., reef environment was measured. Viral abundance was measured by transmission electron microscope direct counts and plaque titer on specific bacterial hosts in water and sediment samples from Florida Bay (Blackwater Sound) and along a transect from Key Largo to the outer edge of the reef tract in Key Largo Sanctuary. Water column viral direct counts were highest in Blackwater Sound of Florida Bay (1.2 x 10(7) viruses per ml), decreased to the shelf break (1.7 x 10(6) viruses per ml), and were inversely correlated with salinity (r = -0.97). Viral direct counts in sediment samples ranged from 1.35 x 10(8) to 5.3 x 10(8)/cm(3) of sediment and averaged nearly 2 orders of magnitude greater than counts in the water column. Viral direct counts (both sediment and water column measurements) exceeded plaque titers on marine bacterial hosts (Vibrio natriegens and others) by 7 to 8 orders of magnitude. Water column viral abundance did not correlate with bacterial direct counts or chlorophyll a measurements, and sediment viral parameters did not correlate with water column microbial, viral, or salinity data. Coliphage, which are indicators of fecal pollution, were detected in two water column samples and most sediment samples, yet their concentrations were relatively low (<2 to 15/liter for water column samples, and <2 to 108/cm(3) of sediment). Our findings indicate that viruses are abundant in the Key Largo environment, particularly on the Florida Bay side of Key Largo, and that processes governing their distribution in the water column (i.e., salinity and freshwater input) are independent of those governing their distribution in the sediment environment. PMID- 8480999 TI - Microbiological transformations of lipids: acyl-specific hydrolysis of lard by yeasts. AB - The fatty acid and positional specificities of Saccharomyces cerevisiae (UI SACCH) and Schizosaccharomyces octosporus (NRRL Y-854) in the hydrolysis of lard were studied by using gas-liquid chromatography. Synthetic triglycerides were used to determine the positional specificities of the lipases of both organisms. Palmitic acid is specifically cleaved from all three triglyceride ester positions by S. cerevisiae, while S. octosporus was able to cleave stearic acid at either position 1 or position 3 of the glycerol moiety. Preparative scale fermentation with 200 g of lard per liter yielded 48.4 g of palmitic acid per liter with S. cerevisiae and 42 g of stearic acid per liter with S. octosporus. The free fatty acids produced by microbial transformation of lard were characterized spectrally (1H and C nuclear magnetic resonance and mass spectrometry) and chromatographically (thin-layer and gas chromatographies). PMID- 8481000 TI - Production of high concentrations of ethanol from inulin by simultaneous saccharification and fermentation using Aspergillus niger and Saccharomyces cerevisiae. AB - Pure nonhydrolyzed inulin was directly converted to ethanol in a simultaneous saccharification and fermentation process. An inulinase-hyperproducing mutant, Aspergillus niger 817, was grown in a submerged culture at 30 degrees C for 5 days. The inulin-digestive liquid culture (150 ml) was supplemented with 45 g of inulin, 0.45 g of (NH4)2SO4, and 0.15 g of KH2PO4. The medium (pH 5.0) was inoculated with an ethanol-tolerant strain, Saccharomyces cerevisiae 1200, and fermentation was conducted at 30 degrees C. An additional 20 g of inulin was added to the culture after 15 h of fermentation. S. cerevisiae 1200 utilized 99% of the 65 g of inulin during the fermentation, and produced 20.4 and 21.0% (vol/vol) ethanol from chicory and dahlia inulins, respectively, within 3 days of fermentation. The maximum volumetric productivities of ethanol were 6.2 and 6.0 g/liter/h for chicory and dahlia inulins, respectively. The conversion efficiency of inulin to ethanol was 83 to 84% of the theoretical ethanol yield. PMID- 8481001 TI - Glucose and carbon dioxide metabolism by Succinivibrio dextrinosolvens. AB - Growth rates and culture conditions affect the molar yields of catabolic end products and cells of Succinivibrio dextrinosolvens growing on glucose. When growth in chemostats occurred, a trend toward decreased succinate and acetate formation, increased lactate formation, and a higher yield of cells correlated with an increase in the growth rate. End product and cellular yields on defined medium indicate a high maintenance requirement for S. dextrinosolvens and are consistent with energy conservation steps during the formation of acetate and succinate. Simultaneous carbon dioxide consumption and production were determined from batch studies with NaH14CO3, and the amounts were used to calculate a fermentation balance. These data also indicated that CO2 consumption lags behind CO2 production early in the growth phase, becoming equivalent to it toward stationary phase. Significantly more CO2 was fixed by S. dextrinosolvens when the organism was cultured in chemostats sparged with CO2. Formate is in part derived from free CO2 in the medium, as shown by 13C nuclear magnetic resonance studies, and may be sensitive to CO2 availability. Nuclear magnetic resonance data are consistent with the carboxylation of a C3 intermediate of the Embden-Meyerhof Parnas pathway of glycolysis to a C4 compound to eventually form succinate. PMID- 8481002 TI - Degradation of benzene, toluene, ethylbenzene, and xylenes (BTEX) by the lignin degrading basidiomycete Phanerochaete chrysosporium. AB - Degradation of the BTEX (benzene, toluene, ethylbenzene, and o-, m-, and p xylenes) group of organopollutants by the white-rot fungus Phanerochaete chrysosporium was studied. Our results show that the organism efficiently degrades all the BTEX components when these compounds are added either individually or as a composite mixture. Degradation was favored under nonligninolytic culture conditions in malt extract medium, in which extracellular lignin peroxidases (LIPs) and manganese-dependent peroxidases (MNPs) are not produced. The noninvolvement of LIPs and MNPs in BTEX degradation was also evident from in vitro studies using concentrated extracellular fluid containing LIPs and MNPs and from a comparison of the extents of BTEX degradation by the wild type and the per mutant, which lacks LIPs and MNPs. A substantially greater extent of degradation of all the BTEX compounds was observed in static than in shaken liquid cultures. Furthermore, the level of degradation was relatively higher at 25 than at 37 degrees C, but pH variations between 4.5 and 7.0 had little effect on the extent of degradation. Studies with uniformly ring-labeled [14C]benzene and [14C]toluene showed substantial mineralization of these compounds to 14CO2. PMID- 8481003 TI - Antibody-magnetite method for selective concentration of Giardia lamblia cysts from water samples. AB - An antibody-magnetite method was developed in order to selectively concentrate Giardia cysts from water samples. The indirect technique employed a mouse immunoglobulin G anti-Giardia antibody as a primary antibody and an anti-mouse immunoglobulin G antibody-coated magnetite particle as a secondary labeling reagent. The magnetically labeled cysts were then concentrated by high-gradient magnetic separation. Ninety percent of the seeded cysts were recovered from buffer when this method was employed. An average of 82% of the seeded cysts were recovered from water samples with various turbidities. Significantly higher cyst recoveries were obtained from water samples with turbidities below 600 nephelometric turbidity units. PMID- 8481004 TI - ScrFI restriction-modification system of Lactococcus lactis subsp. cremoris UC503: cloning and characterization of two ScrFI methylase genes. AB - Two genes from the total genomic DNA of dairy starter culture Lactococcus lactis subsp. cremoris UC503, encoding ScrFI modification enzymes, have been cloned and expressed in Escherichia coli. No homology between the two methylase genes was detected, and inverse polymerase chain reaction of flanking chromosomal DNA indicated that both were linked on the Lactococcus genome. Neither clone encoded the cognate endonuclease. The DNA sequence of one of the methylase genes (encoded by pCI931M) was determined and consisted of an open reading frame 1,170 bp long, which could encode a protein of 389 amino acids (M(r), 44.5). The amino acid sequence contained the highly characteristic motifs of an m5C methylase. Extensive regions of homology were observed with the methylases of NlaX, EcoRII, and Dcm. PMID- 8481005 TI - Evaluation of colilert-marine water for detection of total coliforms and Escherichia coli in the marine environment. AB - A test that allows for early detection of fecally contaminated coastal water would enhance public health protection. Colilert-Marine Water (Colilert-MW; Environetics, Branford, Conn.) is a rapid 24-h test that has recently been developed to detect total coliforms and Escherichia coli in coastal water. We performed a premarketing evaluation of the Colilert-MW product, testing it in parallel with the multiple tube fermentation (MTF) method for 86 coastal water samples in southern California. Statistical analysis was performed by using paired t tests and linear regression. Bacterial isolates were evaluated by biochemical and genetic analysis. The results of this study showed a strong correlation between the traditional MTF and the Colilert-MW method for detection of total coliforms (r = 0.95) and E. coli (r = 0.89) in ocean water samples. Paired t-test results indicated that the Colilert-MW and MTF were equivalent in detecting E. coli and that the Colilert-MW may be more sensitive in the detection of total coliforms. We conclude that Colilert-MW would be a useful tool with which to monitor coastal beach water. PMID- 8481006 TI - Identification of metabolites from the degradation of fluoranthene by Mycobacterium sp. strain PYR-1. AB - Mycobacterium sp. strain PYR-1, previously shown to extensively mineralize high molecular-weight polycyclic aromatic hydrocarbons in pure culture and in sediments, degrades fluoranthene to 9-fluorenone-1-carboxylic acid. In this study, 10 other fluoranthene metabolites were isolated from ethyl acetate extracts of the culture medium by thin-layer and high-performance liquid chromatographic methods. On the basis of comparisons with authentic compounds by UV spectrophotometry and thin-layer chromatography as well as gas chromatography mass spectral and proton nuclear magnetic resonance spectral analyses, the metabolites were identified as 8-hydroxy-7-methoxyfluoranthene, 9 hydroxyfluorene, 9-fluorenone, 1-acenaphthenone, 9-hydroxy-1-fluorenecarboxylic acid, phthalic acid, 2-carboxybenzaldehyde, benzoic acid, phenylacetic acid, and adipic acid. Authentic 9-hydroxyfluorene and 9-fluorenone were metabolized by Mycobacterium sp. strain PYR-1. A pathway for the catabolism of fluoranthene by Mycobacterium sp. strain PYR-1 is proposed. PMID- 8481007 TI - High-level cryIVD and cytA gene expression in Bacillus thuringiensis does not require the 20-kilodalton protein, and the coexpressed gene products are synergistic in their toxicity to mosquitoes. AB - Interactions among the 20-kDa protein gene and the cytA and cryIVD genes located in a 9.4-kb HindIII fragment were studied. A series of plasmids containing a combination of these different genes was constructed by using the Escherichia coli/Bacillus thuringiensis shuttle vector pHT3101. The plasmids were then used to transform an acrystalliferous strain, cryB, derived from B. thuringiensis subsp. kurstaki. The results from sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses suggest that although the 20-kDa protein is required for the efficient CytA protein production in E. coli, it is not required in B. thuringiensis. With or without the truncated 20-kDa protein gene, the CtyA and/or CryIVD proteins are produced and form parasporal inclusions in B. thuringiensis cells. However, more-efficient expression is obtained when a second protein, probably acting as a chaperonin, is present. In addition, the time course studies show that the CytA and CryIVD proteins are coordinately produced. Both the crude B. thuringiensis culture and purified inclusions from each recombinant B. thuringiensis strain are toxic to Culex quinquefasciatus larvae. The parasporal inclusions formed in B. thuringiensis cells are mosquitocidal, with CytA synergizing CryIVD toxicity. PMID- 8481008 TI - Aspartate aminotransferase and tylosin biosynthesis in Streptomyces fradiae. AB - Aspartate aminotransferase as well as valine dehydrogenase and threonine dehydratase was required for the biosynthesis of tylosin in Streptomyces fradiae NRRL 2702. The biosynthesis of these enzymes and tylosin production were repressed by high concentrations of ammonium ions. The change in specific tylosin production rates in batch cultures with different initial concentrations of ammonium ions showed patterns similar to those of the specific production rates of aspartate aminotransferase, valine dehydrogenase, and threonine dehydratase. Aspartate aminotransferase has been purified by acetone precipitation, DEAE cellulose, hydroxyapatite, and preparative electrophoresis chromatographies. The purified enzyme (120 kDa) consisted of two subunits identical in molecular mass (54 kDa) and showed homogeneity, giving one band with a pI of 4.2 upon preparative isoelectric focusing. The enzyme was specific for L-aspartate in the forward reaction; the Km values were determined to be 2.7 mM for L-aspartate, 0.7 mM for 2-oxyglutarate, 12.8 mM for L-glutamate, and 0.15 mM for oxaloacetate. The enzyme was somewhat thermostable, having a maximum activity at 55 degrees C, and had a broad pH optimum that ranged from 5.5 to 8.0. The mode of action was a ping pong-bi-bi mechanism. PMID- 8481009 TI - Isolation and characterization of an extracellular glycosylated protein complex from Clostridium thermosaccharolyticum with pectin methylesterase and polygalacturonate hydrolase activity. AB - An extracellular protein complex was isolated from the supernatant of a pectin limited continuous culture of Clostridium thermosaccharolyticum Haren. The complex possessed both pectin methylesterase (EC 3.1.1.11) and exo-poly-alpha galacturonate hydrolase (EC 3.2.1.82) activity and produced digalacturonate from the nonreducing end of the pectin chain. The protein consisted of 230- and 25-kDa subunits. The large subunit contained 10% (wt/wt) sugars (N-acetylgalactosamine and galactose). Under physiological conditions both activities acted in a coordinated manner: the ratio between methanol and digalacturonate released during degradation was constant and equal to the degree of esterification of the pectin used. Prolonged incubation of the enzyme with pectin led to a nondialyzable fraction that was enriched in neutral sugars, such as arabinose, rhamnose, and galactose; the high rhamnose/galacturonic acid ratio was indicative of hairy region-like structures. The smallest substrate utilized by the hydrolase was a tetragalacturonate. Vmax with oligogalacturonates increased with increasing chain length. The Km and Vmax for the polygalacturonate hydrolase with citrus pectate as a substrate were 0.8 g liter-1 and 180 mumol min-1 mg of protein-1, respectively. The Km and Vmax for the esterase with citrus pectin as a substrate were 1.2 g liter-1 and 440 mumol min-1 mg of protein-1, respectively. The temperature optima for the hydrolase and esterase were 70 and 60 degrees C, respectively. Both enzyme activities were stable for more than 1 h at 70 degrees C. The exo-polygalacturonate hydrolase of Clostridium thermosulfurogenes was partially purified while the methylesterase was also copurified. PMID- 8481010 TI - Selection of Pseudomonas sp. strain HBP1 Prp for metabolism of 2-propylphenol and elucidation of the degradative pathway. AB - A mutant of Pseudomonas sp. strain HBP1, originally isolated on 2 hydroxybiphenyl, was selected for the ability to grow on 2-propylphenol as the sole carbon and energy source. In the mutant strain, which was designated as Pseudomonas sp. strain HBP1 Prp, the cellular induction mechanism involved in the synthesis of the NADH-dependent monooxygenase is changed. 2-Propylphenol, which is known to be a substrate of the monooxygenase, does not induce formation of the monooxygenase in the wild type but does have an induction effect in the mutant strain. Furthermore, in contrast to the wild type, mutant strain HBP1 Prp constitutively produces a small amount of monooxygenase and metapyrocatechase. The enzymes from strain HBP1 Prp catalyzing the first three steps in the degradation of 2-propylphenol--the NADH-dependent monooxygenase, the metapyrocatechase, and the meta fission product hydrolase--were partially purified, and their activities were measured. The product of the monooxygenase activity was identified by mass spectrometry as 3-propylcatechol. The metapyrocatechase used this compound as a substrate and produced a yellow meta fission product that was identified by mass spectrometry as 2-hydroxy-6-oxo-nona 2,4- dienoate. Butyrate could be detected as a product of the meta fission product hydrolase in crude cell extract of 2-propylphenol-grown cells, as well as an intermediate in culture broths during growth on 2-propylphenol. All three enzymes expressed highest activities for the metabolites of the degradation of 2 hydroxybiphenyl. PMID- 8481011 TI - Survival of nonculturable Aeromonas salmonicida in lake water. AB - The survival of Aeromonas salmonicida subsp. salmonicida was investigated in sterile and untreated lake water. In sterile lake water (filtered and autoclaved), it was found that cells of A. salmonicida entered a nonculturable but viable condition. Viability was determined by flow cytometry with the dye rhodamine 123, which is taken up and maintained within cells with a membrane potential. For survival studies in untreated lake water, A. salmonicida was marked with the xylE gene by using the plasmid pLV1013. Marked cells were detected by growth on tryptone soy agar and tryptone soy agar supplemented with kanamycin. Cells were also detected by polymerase chain reaction DNA amplification of the xylE gene and a chromosomal DNA fragment specific for A. salmonicida (pLV1013). The results indicated that A. salmonicida entered a nonculturable condition in untreated lake water over a 21-day study. The viability of nonculturable cells could not be determined in mixed samples; however, the presence of nonculturable cells containing both chromosomal and plasmid DNA was confirmed. PMID- 8481012 TI - Quality control of bacterial enumeration. AB - Standard bacterial suspensions can be used to assess test method performance, via control charts, and inhibition of recovery when analyzing water samples. Variability in standard suspensions prepared from different strains and species and the use of frozen environmental samples for quality control for spore and bacteriophage analyses are also discussed. PMID- 8481013 TI - Purification, characterization, gene cloning, and sequencing of a new beta glucosidase from Bacillus circulans subsp. alkalophilus. AB - An intracellular beta-glucosidase was purified from cell extracts of Bacillus circulans subsp. alkalophilus by NAD affinity and high-performance anion-exchange chromatographies. The enzyme was active against a wide range of aryl-beta glucosides and beta-linked disaccharides. The structural gene for beta glucosidase was cloned in Escherichia coli. The beta-glucosidase gene consisted of an open reading frame of 1,350 bp encoding a protein of 450 amino acids with a calculated M(r) of 51,303. The enzyme exhibited from 45 to 66% identity with five bacterial beta-glucosidases. PMID- 8481014 TI - Comparison of fluorescent gentamicin-thallous-carbonate and KF streptococcal agars to enumerate enterococci and fecal streptococci in meats. AB - Two selective and differential media were compared for their abilities to enumerate enterococci and fecal streptococci in pork, beef, and poultry products. Counts obtained on KF streptococcal (KF) agar were compared with counts obtained on fluorescent gentamicin-thallous-carbonate (fGTC) agar. Reactions of 13 known enterococcal species were also observed. All 13 species of enterococci as well as Streptococcus bovis and Streptococcus equinus grew equally well on fGTC agar. KF streptococcal medium allowed growth of most species of enterococci but not S. bovis and S. equinus. Quantitative comparisons between the two media inoculated with pure cultures of known species of enterococci revealed equivalent plate counts following incubation. However, when meat samples were plated, counts on fGTC agar were consistently and significantly higher than counts on KF agar for all sample sources. PMID- 8481015 TI - Comparison of chemical assay, bioassay, enzyme-linked immunosorbent assay, and dot blot hybridization for detection of aerobactin in members of the family Enterobacteriaceae. AB - In order to determine the best strategy for detection of aerobactin in members of the family Enterobacteriaceae, we compared the results of three phenotypic assays, including a chemical assay, a cross-feeding bioassay, and an enzyme linked immunosorbent assay (ELISA), with the results of a dot blot hybridization assay using a specific probe for the aerobactin genes. The sensitivity and specificity of the ELISA were better than those of the chemical and cross-feeding assays, but the results of dot blot hybridization were the most reproducible. However, none of the Serratia and Enterobacter cloacae strains which produced aerobactin hybridized with the probe. We concluded that the best strategy for aerobactin detection is a two-step procedure that combines screening by dot blot hybridization with an ELISA for negative strains. PMID- 8481016 TI - Treatment of a Nocardia brasiliensis mycetoma with sulfamethoxazole and trimethoprim, amikacin, and amoxicillin and clavulanate. PMID- 8481017 TI - A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching. AB - BACKGROUND AND DESIGN: Based on potential contributions of mast cells to neurofibroma-associated itching, pain, and tenderness, the mast cell blocker ketotifen fumarate (Zaditen, Sandoz Pharmaceuticals Corp, Hanover, NJ) has been proposed as a treatment for these symptoms. To test the hypothesis that ketotifen decreases neurofibroma-associated itching, pain, and tenderness, data were accumulated from two protocols. The first was an open-label protocol involving 25 patients with relatively severe symptoms (1170 patient-months), and the second was a double-blind protocol involving 27 patients with either relatively mild or severe neurofibroma-associated symptoms (316 patient-months). All subjects received either oral placebo or 2 to 4 mg of ketotifen fumarate per day. Using a scale of 1 to 10, symptoms were measured before, during, and after treatment. RESULTS: Itching severity scores (means) were as follows: for all patients receiving ketotifen, 7.8 before, 2.8 during, and 7.2 after treatment; for ketotifen-treated patients in the double-blind protocol, 6.6 before, 3.9 during, and 6.4 after treatment; and for placebo-treated patients, 6.0 before and 6.0 during treatment. Pain and tenderness severity scores (means) were as follows: for all patients treated with ketotifen, 7.6 before, 3.6 during, and 6.6 after treatment; for double-blind ketotifen-treated patients, 6.3 before, 4.6 during, and 6.1 after treatment; and for placebo-treated patients, 7.9 before and 6.7 during treatment. CONCLUSIONS: Pretreatment, treatment, and posttreatment levels of itching, pain, and tenderness associated with neurofibromas, using both open label and double-blind protocols, indicate that ketotifen offers a realistic approach to treating these symptoms. PMID- 8481018 TI - Long-term suppression of recurrent genital herpes with acyclovir. A 5-year benchmark. Acyclovir Study Group. AB - BACKGROUND AND DESIGN: This multicenter trial (19 sites) was initiated in 1984 in more than 1100 immunocompetent individuals with a history of frequently recurring genital herpes (mean, > or = 12 episodes per year). The first year of this suppressive therapy trial was placebo controlled, with acyclovir being provided for episodic treatment in both groups. Thereafter, patients were treated with open-label acyclovir suppressive therapy on a long-term basis (400 mg twice daily) to continue to assess its long-term safety and efficacy. Complete data are available on 389 of the 430 patients who began the fifth year of the study. RESULTS: Patients were seen quarterly for review of diaries and clinical laboratory evaluations. The percentage of patients recurrence free for any 3 month quarter of the fifth year ranged from 86% to 90%. The mean annual number of recurrences per patient declined from 1.7 during the first year to 0.8 during the fifth year of suppressive therapy. The frequency of false prodromes has also decreased over time. More than 20% of the patients receiving suppressive therapy for 5 years have been recurrence free the entire time. The duration of herpetic outbreaks during suppressive therapy has not changed. CONCLUSION: This study extends the safety and efficacy profile of oral acyclovir in the suppression of genital herpes to 5 years. The majority of the patients were recurrence free on an annual basis during suppressive therapy. Therapy was well tolerated. Acyclovir usage was not associated with serious side effects or cumulative toxicity. PMID- 8481019 TI - Creeping eruption. A review of clinical presentation and management of 60 cases presenting to a tropical disease unit. AB - BACKGROUND AND DESIGN: Cutaneous larva migrans is an infection with a larval nematode, most frequently by dog or cat hookworms. It has a characteristic presentation that is easily recognizable. We reviewed the charts of 60 patients with cutaneous larva migrans who presented to the Tropical Disease Unit, Toronto (Ontario) Hospital, during a 6-year period. RESULTS: Ninety-five percent of the patients were Canadians who had recently returned from the tropics or subtropics, notably the Caribbean. Almost all patients had a linear or serpiginous, very pruritic larval track. Topical thiabendazole was efficacious in 52 (98%) of 53 patients treated. Albendazole cured six (88%) of seven patients treated. Because of adverse effects, oral thiabendazole and liquid nitrogen were not utilized. CONCLUSION: We conclude that topical thiabendazole and oral albendazole are very effective and safe modalities for the treatment of cutaneous larva migrans. PMID- 8481020 TI - Studies on the repopulation of Langerhans cells in partial-thickness wounds. Air exposed and occlusively dressed. AB - BACKGROUND AND DESIGN: The use of occlusive dressings on partial-thickness wounds has been shown to promote early epithelization and connective tissue regeneration. Because Langerhans cells (LC) have been implicated in epidermal homeostasis we studied the rate of repopulation of LC in air-exposed vs occlusively dressed wounds. Partial-thickness wounds on the backs of pigs were treated with occlusive dressings (Tegaderm) for 3 days or left air exposed. On days 3, 5, 7, and 11 after keratome wounding, epidermal sheets from the regenerating wounds were isolated and stained for LC using indirect immunofluorescence. The LC populations were quantified in the interfollicular regions and expressed as average number of cells per square millimeter of epidermis. RESULTS: Normal skin control had 1024 +/- 93 LC/mm2 distributed uniformly. On day 3 after wounding occlusive-dressing-treated wounds had an LC repopulation of 46% of the original value. Langerhans cells in air-exposed skin could not be evaluated until epithelization occurred at day 5. Langerhans cells in both air-exposed and occlusive-dressing-treated wounds were 46% to 51%, 65% to 71%, and 91% of normal value, respectively, on days 5, 7, and 11. CONCLUSIONS: We conclude that at least in regenerating epidermis, the degree of repair of the new epidermis apparently plays a limited role in the migration of LC, as does the earlier growth of blood vessels. PMID- 8481021 TI - Autoimmune pemphigus. A distinct staining pattern with an anti-desmoglein antibody. AB - BACKGROUND AND DESIGN: Diagnosis of autoimmune pemphigus is based on the immunodetection of IgG deposits in the epidermal intercellular spaces. Desmoglein is a desmosomal component that has been assumed to be the antigen of pemphigus foliaceus. We investigated the use of one monoclonal antibody (32-2B) to desmoglein 1 on paraffin sections. Twenty-nine pemphigus samples were studied (22 pemphigus vulgaris, seven pemphigus foliaceus). RESULTS: In 29 patients suffering from autoimmune pemphigus, the staining for desmoglein was represented by coarse granules along the cytoplasmic borders of epithelial cells in lesional and perilesional skin and in mucous membranes. This peculiar staining is different from the fine dots along the cytoplasmic membrane observed in normal skin. This abnormal staining seems to be specific for pemphigus. Hereditary acantholytic diseases and other diseases such as bullous pemphigoid, intraepidermal IgA dermatosis, eczema, herpes, and transient acantholytic dermatosis show a similar pattern to normal skin. CONCLUSION: The use of 32-2B on biopsy specimens in cases of autoimmune pemphigus demonstrated a specific staining pattern. It could be used on paraffin sections as a diagnostic test of autoimmune pemphigus. It can even be done retrospectively. PMID- 8481022 TI - The distribution of IgA pemphigus antigen in human skin and the role of IgA anti cell surface antibodies in the induction of intraepidermal acantholysis. AB - BACKGROUND AND DESIGN: IgA pemphigus is an uncommon intraepidermal vesiculopustular disease that has clinical and histologic similarity to subcorneal pustular dermatosis and pemphigus foliaceus. All patients have IgA antibodies bound to the epidermal cell surface, and half of the patients have circulating IgA anti-cell surface antibodies detected by standard immunofluorescence testing. We studied the distribution of IgA pemphigus antigen in human skin and the pathogenetic role of circulating IgA antibodies in the induction of intraepidermal vesicle formation. We used skin specimens from numerous sites of two cadavers, as well as from neonatal foreskin, and serum specimens of two patients with IgA pemphigus. OBSERVATIONS: Organ culture and immunofluorescence studies revealed the following: (1) IgA pemphigus antibodies bound preferentially to the granular layer in the vast majority of skin sites that were tested. In one cadaver, binding was preferential to the spinous layer of plantar and buttock skin. No binding was observed in oral and esophageal mucosa. (2) Neither bound nor circulating IgA antibody was complement fixing. (3) One IgA pemphigus serum specimen that was negative by standard immunofluorescence had IgA antibodies that bound the epidermal cell surface after incubation under explant culture conditions. (4) Both IgA pemphigus serum specimens induced acantholysis in skin explant cultures. CONCLUSIONS: When antibodies from one IgA pemphigus serum specimen are used, the expression of IgA pemphigus antigen in human skin shows regional variability, interindividual variability, and variability in the microscopic distribution within the epidermal cell layers. IgA pemphigus antibodies play a role in the pathogenesis of IgA pemphigus. The skin explant culture is more sensitive than is standard immunofluorescence to detect circulating IgA antibodies. PMID- 8481023 TI - Childhood discoid lupus erythematosus. AB - BACKGROUND: Discoid lupus erythematosus (DLE) is uncommon in childhood. Less than 2% of patients with DLE develop the disease before 10 years of age. OBSERVATIONS: We present eight cases of childhood DLE with onset before age 10 years: four black boys with cutaneous DLE, three black girls ages 7, 2, and 6 years at onset, who developed systemic lupus erythematosus at ages 12, 9, and 8 years, respectively, and a 10-year-old Hispanic boy who had a systemic flare at the age of 20 years. CONCLUSIONS: A review of the 16 published cases of childhood DLE reveals that it is similar to its adult counterpart in its presentation and chronic course. However, several important differences are noted: a lack of female predominance, a low incidence of photosensitivity, and frequent progression to systemic lupus erythematosus at an early age. A discussion of the management of DLE in children is also presented. PMID- 8481024 TI - Drug therapy for neurofibromatosis? PMID- 8481025 TI - Multiple black nodules on the thumb. Dorsal mucoid cysts of the finger. PMID- 8481026 TI - Superficial erosions with some oozing and marked crusting. Pemphigus erythematosus (PE). PMID- 8481027 TI - A solitary plaque of the cheek--granuloma faciale. PMID- 8481028 TI - Burning discomfort and swelling of the hands and face of a young child. Erythropoietic protoporphyria (EPP). PMID- 8481029 TI - Recall of cutaneous toxicity from fluorouracil. PMID- 8481030 TI - Lack of serum selenium rise after overnight application of selenium sulfide. PMID- 8481031 TI - Secondary hyperparathyroidism in patients with ichthyosis is not caused by vitamin D deficiency or ingestion of retinoids. PMID- 8481032 TI - Caustic ingestion. PMID- 8481033 TI - Failure to thrive in congenital heart disease. PMID- 8481034 TI - Renal stone disease--investigative aspects. PMID- 8481035 TI - Gastrointestinal morbidity and growth after repair of oesophageal atresia and tracheo-oesophageal fistula. AB - Upper gastrointestinal morbidity and anthropometric data in 334 patients aged 1 to 37 years with repaired oesophageal atresia and tracheo-oesophageal fistula are reported. Two thirds were subsequently hospitalised with oesophageal complications and half underwent one or more surgical procedures. Thirteen percent were hospitalised for more than 50 days. Anastomotic strictures were present in one third and just under half had gastro-oesophageal reflux. Dysphagia was present in about 65% in all age groups but symptom severity and surgical intervention decreased significantly after 5 years of age. Gastro-oesophageal reflux symptoms were commoner in the older patients increasing from 18% in the group under 5 years of age to 52% in those over 15 years. Height centile distribution was normal, but the median weight centile was the 25th. Weight for height values greater than 2 SD below the mean were present in 13%, and two thirds of these patients were under 5 years of age. The majority of adults enjoyed a normal lifestyle and were comparable with their peers. PMID- 8481036 TI - Respiratory morbidity after repair of oesophageal atresia and tracheo-oesophageal fistula. AB - Respiratory morbidity in 334 patients aged 1 to 37 years with repaired oesophageal atresia and tracheo-oesophageal fistula is reported. Just under half the patients were subsequently hospitalised with respiratory illness. Two thirds of admissions were before 5 years of age. Five percent were admitted on more than five occasions. Patients with gastro-oesophageal reflux and low birth weight were more likely to be admitted. Thirty one percent of patients had one or more episodes of pneumonia in the first five years of life and 5% after 15 years. The prevalence of annual bouts of bronchitis in these age groups was 74% and 41% respectively. The prevalence of wheeze was about 40% in all age groups. Patients with symptoms persisting after 15 years were more likely to have had lower respiratory tract illness in early childhood and a history of atopy. In the 12 months before review, weekly episodes of wheezing were present in one third under 5 years and 15% over 15 years. Thirty two percent of patients aged 5-10 years and 8% over 15 years missed two or more weeks of school or work in the previous year with respiratory illness. PMID- 8481037 TI - Investigation of vascular compression of the trachea: the complementary roles of barium swallow and echocardiography. AB - To determine the preferred investigation of congenital vascular compression of the trachea, preoperative investigation in 40 patients undergoing surgery 1981-91 was analysed. The importance of preoperative identification of detailed arterial anatomy in determining surgical technique was also assessed in 122 consecutive patients undergoing surgery 1952-91. Of the 40 patients (median age 5 months) seen 1981-91, barium swallow before referral suggested the diagnosis of vascular compression in 26 of 27 (96%). Angiography (1/3), bronchoscopy (0/6), and echocardiography (2/6) were generally unhelpful in diagnosing vascular compression before referral. Echocardiography was performed after referral in 18 consecutive patients since 1986 and the correct arterial anatomy was identified in 16 (88%); hyperinflation resulted in inadequate images in the two others. Barium swallow is the investigation of choice to screen for suspected vascular compression of the trachea; echocardiography at the referral centre can define the arterial anatomy in nearly all patients. Further investigation can be reserved for selected cases. PMID- 8481038 TI - The natural history of congenital myotonic dystrophy: mortality and long term clinical aspects. AB - Although the genetic basis of the congenital form of myotonic dystrophy has recently been clarified, data as to outcome in terms of life expectancy and morbidity are scanty. Life table data based on a cohort of 115 patients with a confirmed diagnosis of congenital myotonic dystrophy are presented. The data suggest a 25% chance of death before 18 months of age and a 50% chance of survival into the mid-30s. The profile of disease and complications among survivors is also charted. PMID- 8481039 TI - Coronary risk factors in schoolchildren. AB - Death rates from coronary heart disease (CHD) in Northern Ireland are among the highest in the world. However, no data have been available to test the hypothesis that the high prevalence of CHD is reflected by the risk status of the childhood population. A randomly selected 2% population sample of 1015 children aged 12 and 15 years was studied to obtain baseline information on blood pressure, lipid profile, cigarette smoking, family history, physical activity, cardiorespiratory fitness, and dietary fat intake. Using available criteria thresholds, 15-23% displayed increased blood pressure, 12-25% had unfavourable lipid profiles, and 18-34% were overfat. In 15 year old children, 16-21% admitted being regular smokers, 26-34% displayed poor cardiorespiratory fitness, and 24-29% reported little physical activity in the previous week. Dietary analysis revealed relatively low polyunsaturated to saturated fatty acid ratios and high mean fat intakes, accounting for approximately 40% total daily energy. Despite the exclusion of family history from the analysis, 16% of the older children exhibited three or more risk factors. These results justify major concern about the level of potential coronary risk in Northern Ireland schoolchildren. Broadly based primary prevention strategies aimed at children are essential if future adult CHD mortality is to be reduced. PMID- 8481040 TI - Noonan's and DiGeorge syndromes with monosomy 22q11. AB - A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome. PMID- 8481041 TI - International trends in pedestrian injury mortality. AB - Trends in pedestrian injury mortality for children aged 0-4 and 5-14 for England and Wales, Denmark, Sweden, the USA, and New Zealand were examined from 1968 onwards. While there has been a reduction in the pedestrian mortality in all these countries, there are striking international differences in the extent of these reductions. Denmark has achieved the greatest fall in mortality with the smallest decrease seen in New Zealand. Countries which have experienced major decreases in pedestrian mortality are distinguished by having placed greater emphasis on environmentally based prevention strategies rather than pedestrian skills education. PMID- 8481042 TI - Metabolic effects of growth hormone treatment: an early predictor of growth response? AB - Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months. PMID- 8481044 TI - An improved clinical method for detecting meningeal irritation. AB - Neck stiffness is the most important sign of meningitis. When the neck is flexed, the inflamed nerve roots and meninges of the cervical region get stretched. This causes protective muscle spasm manifesting as neck stiffness. Kernig's sign represents similar phenomena involving the distal spinal cord and related nerves. A manoeuvre that stretches the neural elements of the whole length of the spinal canal simultaneously will be a more sensitive test for meningeal irritation. Eliciting neck stiffness while the patient sits up with knees extended achieves this. This method is more sensitive, specific, and amenable to objective assessment. PMID- 8481043 TI - Serum amyloid A protein in acute viral infections. AB - Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID- 8481045 TI - Injuries in primary care practices. AB - A study of injuries among 0-15 year old children attending primary care clinics in a low social class and a middle class neighbourhood was carried out during a period of one year. Data were collected in a structured form by the physicians while the patient was in the clinic. The rate of injuries was 121.3/1000 children per year in the clinic from the lower social class neighbourhood and 70.7/1000 children per year in the clinic from the middle class neighbourhood. Injuries in playgrounds, and on pavements and streets occurred in higher proportions in the low social class than in the middle class neighbourhood clinics. The most frequent causes of injuries were falls and being struck and injured by cutting/piercing instruments; these caused mostly contusions and lacerations. The clinic was the first place of treatment in 65% of the cases in the middle class area and in 45% in the lower social class area; 28% and 10% respectively were referred to the hospital for additional treatment. Data from primary care clinics should be considered when estimating the incidence of injuries in the community, in planning intervention programmes, and future research. PMID- 8481046 TI - Growth hormone deficiency and combined immunodeficiency. AB - The first description of an association of isolated growth hormone deficiency (IGHD) and combined immunodeficiency is presented. The findings suggest that IGHD should be considered as a cause of short stature in children with combined immunodeficiency before attributing growth retardation to infection. PMID- 8481047 TI - Hyperphosphataemia after enemas in childhood: prevention and treatment. AB - The case of a child with severe hyperphosphataemia and symptomatic hypocalcaemia secondary to retention of phosphate administered through an antegrade continence enema is reported. Caution should be exercised with the use of phosphate enemas and prompt action taken to remedy retention. The use of glucose with insulin in the emergency management of acute hyperphosphataemia is discussed. PMID- 8481048 TI - Compliance with antibiotic prophylaxis in urinary tract infection. AB - Compliance with antibiotic prophylaxis after urinary tract infection was assessed in 32 children, using a parent questionnaire, and a urine test for antibacterial substances. In 31 (97%) cases, parents reported giving the antibiotics every day but only 22 (69%) of urine tests were positive. Failure to understand the reasons for prophylaxis and non-compliance were significantly associated. PMID- 8481049 TI - Cycle helmets. PMID- 8481051 TI - Counted data (1). PMID- 8481050 TI - Cows' milk induced intestinal bleeding in infancy. PMID- 8481052 TI - Infant rib fracture--birth trauma or non-accidental injury. PMID- 8481053 TI - Mycoplasma and thrombocytopenia. PMID- 8481054 TI - Synovial lymphocytes and the aetiology of synovitis. PMID- 8481055 TI - Role of protein glycosylation in immune regulation. PMID- 8481056 TI - A walk round the edges of self tolerance. PMID- 8481057 TI - A reappraisal of the evidence that rheumatoid arthritis and several other idiopathic diseases are slow bacterial infections. PMID- 8481058 TI - Molecular and cellular mechanisms of joint destruction in rheumatoid arthritis: two cellular mechanisms explain joint destruction? PMID- 8481059 TI - IgG3 cryoglobulins in autoimmune MRL-lpr/lpr mice: immunopathogenesis, therapeutic approaches and relevance to similar human diseases. AB - MRL-lpr/lpr mice spontaneously develop an autoimmune disease resembling systemic lupus erythematosus and rheumatoid arthritis. One of the unique serological abnormalities in this strain is remarkably high concentrations of cryoglobulins. Analysis of immunoglobulin components in their cryoglobulins has shown selective enrichment of a particular IgG subclass, IgG3. As IgG3 enrichment is also found in two other cryoglobulins, which are induced after injection with bacterial lipopolysaccharides or infection with malaria, IgG3 apparently represents a major source of murine cryoglobulins. Studies on murine IgG3 monoclonal antibodies (mAbs) have clearly shown that murine IgG3 have the unique physiochemical property to self associate through non-specific IgG3 Fc-Fc interaction, and that most of them can generate monoclonal cryoglobulins. Most strikingly, IgG3 monoclonal cryoglobulins with rheumatoid factor (RF) activity induce extensive pathological manifestations: skin vascular purpura and glomerulonephritis with 'wire loop' lesions. Although the cryoglobulin activity of IgG3 RF mAb is solely responsible for the generation of glomerular lesions (both RF and cryoglobulin activities are necessary for skin vascular lesions), the absence of nephritogenic activity by some IgG3 cryoglobulins supports the idea that qualitative features of cryoglobulins are critical to determine their pathogenic activity. The demonstration of a positive correlation between the production of IgG3 cryoglobulins and the development of lupus nephritis in MRL-lpr/lpr mice further substantiates the pathological importance of cryogenic autoantibodies. On the other hand, it should be emphasised that non-cryogenerating IgG3 autoantibodies may not be harmful, but even protective, as a result of their interaction with pathogenic IgG3 cryoglobulins. Finally, the development of an experimental model of cryoglobulinaemia associated with vascular and glomerular disease certainly represents an invaluable opportunity to study the molecular mechanisms responsible for the generation of cryoglobulins and their associated tissue lesions, and also to assess various therapeutic approaches. Our demonstration that anti-idiotypic mAb can prevent the pathogenic effects of the cryoprecipitable IgG3 RF mAb suggests strongly that such a therapeutic approach might be successful in similar diseases in man. PMID- 8481061 TI - Renal failure and hyperkalemia associated with ketorolac tromethamine. AB - Three patients who were treated with ketorolac tromethamine (Toradol), an injectable nonsteroidal anti-inflammatory drug for pain management, developed acute renal failure or hyperkalemia or both. These complications were reversible in two cases after discontinuing the drug. Clinical conditions preexisted in each patient that rendered them susceptible to the renal complications of nonsteroidal anti-inflammatory use. It is well known that caution should be observed while using nonsteroidal anti-inflammatory drugs in patients whose renal function may be preserved through prostaglandin-mediated vasodilatory effects. The same cautions apply to ketorolac. Since its major marketed use is as an analgesic and its potent effect on prostaglandin synthesis may not be well recognized, those cautions must be emphasized. PMID- 8481062 TI - The milk-alkali syndrome. A reversible form of acute renal failure. AB - The milk-alkali syndrome became rare with the advent of modern ulcer therapy with nonabsorbable antacids, histamine2 blockers, and sucralfate. An increased frequency of this syndrome seems likely with the growing popularity of the use of calcium carbonate as an antacid or as calcium supplementation to prevent osteoporosis. We treated five patients who had six episodes of the milk-alkali syndrome; four of these cases were diagnosed between 1990 and 1992. All patients were ingesting massive quantities of calcium and absorbable alkali and were unaware of the toxic effects of these compounds. All patients presented with the triad of hypercalcemia, metabolic alkalosis, and renal failure. All metabolic abnormalities were corrected, and renal function improved with appropriate supportive measures and cessation of calcium and alkali ingestion. In two patients, the renal failure was so severe that dialysis was necessary. In four patients, either the serum amino-terminal parathyroid hormone or 1,25 dihydroxycholecalciferol levels were appropriately decreased in response to hypercalcemia. The serum carboxy-terminal parathyroid hormone levels were increased because of renal failure. Since both physicians and patients are often unaware of the calcium and alkali content of many nonprescription medicines, the diagnosis of the milk-alkali syndrome, a reversible cause of renal failure, can be missed if a detailed history of such intake is not elicited. Measurement of the serum amino-terminal parathyroid hormone and 1,25-dihydroxycholecalciferol levels may help differentiate milk-alkali syndrome from primary hyperparathyroidism. PMID- 8481060 TI - Bacterial and viral superantigens: roles in autoimmunity? AB - Superantigens are bacterial, viral, or retroviral proteins which can activate specifically a large proportion of T cells. In contrast with classical peptide antigen recognition, superantigens do not require processing to small peptides but act as complete or partially processed proteins. They can bind to major histocompatibility complex class II molecules and stimulate T cells expressing particular T cell receptor V beta chains. The other polymorphic parts of the T cell receptor, which are crucial for classical antigen recognition, are not important for this interaction. When this strategy is used a large proportion of the host immune system can be activated shortly after infection. The activated cells have a wide variety of antigen specificities. The ability to stimulate polyclonal B (IgG) as well as T cell responses raises possibilities of a role for superantigens in the induction of autoimmune diseases. Superantigens have been a great tool in the hands of immunologists in unravelling some of the basic mechanisms of tolerance and immunity. PMID- 8481063 TI - Measles susceptibility of hospital personnel. PMID- 8481064 TI - A clinical model for diagnosis of urinary tract infection in young women. PMID- 8481065 TI - Complications of infective endocarditis in the 1980s. PMID- 8481066 TI - Pleasure heals. The role of social pleasure--love in its broadest sense--in medical practice. PMID- 8481067 TI - Cost-effectiveness analysis of various strategies in the diagnostic management of pulmonary embolism. AB - BACKGROUND: Since the clinical diagnosis of pulmonary embolism is unreliable, various objective diagnostic methods (or combinations thereof) are advocated. Pulmonary angiography is the accepted reference method but is considered less suitable for initial screening due to its invasive nature. Therefore, at least nine different diagnostic management strategies employing invasive and noninvasive diagnostic tests are used in clinical practice. We assessed the cost effectiveness of these strategies to help identify the optimal approach. METHODS: Based on assumptions derived from published data, we calculated mortality, morbidity, adequacy for the indication of anticoagulant therapy, and associated diagnostic and therapeutic costs using a decision analytic model. Additionally, a cost-effectiveness analysis was performed using incremental costs per additional life saved. RESULTS: The analysis identified three separate categories of diagnostic management strategies: (1) Treatment of all patients (or of those with an abnormal perfusion scan) results in the lowest mortality and morbidity rates but the highest costs due to inappropriate treatment of 55% to 70% of patients. (2) Pulmonary angiography strategies with or without prior perfusion-ventilation lung scintigraphy and ultrasonography of the legs have comparable low mortality and morbidity rates, costs savings of approximately 40%, and inappropriate treatment in fewer than 5% of patients. (3) Use of perfusion-ventilation scintigraphy with or without ultrasonography results in unacceptably high mortality rates. CONCLUSIONS: At present, the optimal diagnostic management strategy should include pulmonary angiography. Use of perfusion-ventilation lung scintigraphy and ultrasonography results in a 40% to 50% reduction in the number of patients requiring pulmonary angiography and is cost-effective. PMID- 8481068 TI - 'Subclinical hypothyroidism'. Natural course of the syndrome during a prolonged follow-up study. AB - OBJECTIVE: To determine the natural course of the syndrome "subclinical hypothyroidism." DESIGN: Prospective study of 30 subjects with "subclinical hypothyroidism," as documented precisely by normal serum thyroxine and triiodothyronine concentrations and high serum thyrotropin levels on three occasions at intervals of 2 to 3 weeks. The subjects were followed up for 4 to 15 years (mean, 8.2 +/- 2.3 years), with repeated determinations of thyroid hormone indices at intervals of 3 to 6 months. SETTING: Endocrinology Clinic at the Veterans Affairs Medical Center. RESULTS: 16 subjects developed definitive primary hypothyroidism within 3 months to 2 years, as reflected by a progressive rise in serum thyrotropin level with a gradual decline in serum thyroxine and triiodothyronine concentrations, with serum thyroxine levels falling to subnormal concentrations. In 14 of these subjects, primary hypothyroidism could be attributed to known etiologic factors, whereas in the remaining two the cause was not apparent. Persistently elevated serum thyrotropin with normal serum thyroxine and triiodothyronine concentrations following a cyclic pattern was observed in 14 subjects during the follow-up period. In 11 of these subjects, there was a history of non-radical surgery or conventional radiation therapy to the neck area, whereas in the remaining three subjects, no apparent cause could be identified. CONCLUSIONS: "Subclinical hypothyroidism" is not always a forerunner of primary hypothyroidism. Two distinct populations evolve: (1) those with true preclinical or subclinical hypothyroidism, which may be predicted by the presence of one of the well-known etiologic factors responsible for onset of primary hypothyroidism, and (2) euthyroidism with reset thyrostat--a permanent state without a definitive progression to hypothyroidism, most probably secondary to a previous subtle insult to the thyroid gland. PMID- 8481069 TI - Factors predicting improvements in lipid values following cardiac rehabilitation and exercise training. AB - BACKGROUND: Cardiac rehabilitation and exercise training improve prognosis following major cardiac events, partly by improving coronary risk factors, including plasma lipids. Only limited data are available to define predictors of lipid improvements following aggressive nonpharmacologic therapy with cardiac rehabilitation. METHODS: We studied 237 consecutive patients from two institutions who were enrolled in outpatient phase 2 cardiac rehabilitation and exercise programs. By univariable and multivariable analyses, we assessed the impact of numerous clinical variables, including indexes of obesity, age, gender, lipid concentrations, exercise capacity, and psychological factors, on improvements in plasma lipid values with cardiac rehabilitation. RESULTS: Coronary risk factors improved following cardiac rehabilitation, including levels of low-density lipoprotein cholesterol (-4%; P < .05), high-density lipoprotein cholesterol (7%; P < .0001), and triglycerides (-13%; P < .0001); body mass index (-2%; P < .0001); percentage of body fat (-5%; P < .0001); and exercise capacity (26%; P < .0001). By both univariable and multivariable analyses, corresponding dyslipidemic baseline values were the strongest predictors of improvements in levels of low-density lipoprotein cholesterol (univariable: r = .51, P < .0001; multivariable: t = 8.5, P < .0001), high-density lipoprotein cholesterol (univariable: r = .37, P < .0001; multivariable: t = 6.6, P < .0001), and triglycerides (univariable: r = .36, P < .0001; multivariable: t = 6.8, P < .0001). By multivariable analyses, reductions in body mass index (t = 4.6, P < .0001) and older age (t = 4.0, P < .0001) were strong independent predictors of reduction in triglyceride values following cardiac rehabilitation. However, low baseline triglyceride values were independently associated with improvements in both low-density and high-density lipoprotein cholesterol levels. Using a model incorporating 13 clinical variables, improvements in lipid values with cardiac rehabilitation were only modestly predictable with the variables assessed, accounting for only 30% to 40% of the improvements in lipid values. CONCLUSIONS: (1) Coronary risk factors markedly improved following cardiac rehabilitation and exercise training. (2) Improvements in lipid values are modestly predictable. (3) Those patients with the worst baseline lipid values had the most improvements in lipid values following cardiac rehabilitation. However, patients with combined hyperlipidemia and low levels of high-density lipoprotein cholesterol are likely to require drug treatment. PMID- 8481070 TI - Variation in utilization of procedures for treatment of peripheral arterial disease. A look at patient characteristics. AB - OBJECTIVE: To examine associations between demographic characteristics and use of interventional procedures in patients with peripheral arterial disease. DESIGN: Case series drawn from a statewide hospital discharge database. SETTING: Nonfederal acute-care hospitals in Maryland. PATIENTS AND INTERVENTIONS: A total of 7080 cases of angioplasty, bypass surgery, or amputation for lower-extremity peripheral arterial disease in 1988 through 1989. MAIN OUTCOME MEASURE: Use of angioplasty, bypass surgery, and lower-extremity amputation. RESULTS: A total of 1185 angioplasties, 4005 bypass operations, and 1890 amputations were identified. Population-based annual rates showed that angioplasty use peaked at about 70 per 100,000 at the age of 65 to 74 years, bypass surgery use peaked at more than 250 per 100,000 at 75 to 84 years of age, and amputation use peaked at about 225 per 100,000 at 85 years of age and older. The age-adjusted likelihood of having a procedure for peripheral arterial disease was 1.7 times higher in men than in women and 1.6 times higher in blacks than in whites. Compared with patients who had angioplasty or bypass surgery, patients who had amputations were more likely to be more than 65 years old, to be black (odds ratio, 2.5), to have Medicaid or no insurance (odds ratio, 1.7), to have diabetes mellitus (odds ratio, 3.0), and not to have hypertension (odds ratio, 3.1). Compared with patients who had bypass surgery, patients who had angioplasty were more likely to be under 65 years old, to be white (odds ratio, 1.7), and not to have diabetes mellitus (odds ratio, 1.3). CONCLUSION: Patient race is associated with differences in the frequency with which angioplasty, bypass surgery, and amputation are performed for peripheral arterial disease, and insurance status is associated with the likelihood of having amputation. PMID- 8481071 TI - Epidemic obesity in the United States. PMID- 8481072 TI - Changes in undergraduate medical education. A critique. PMID- 8481073 TI - Management of gallstones in diabetic patients. AB - The management of gallstones in diabetic patients has traditionally been considered problematic. Autopsy findings and uncontrolled studies have documented a higher prevalence of cholelithiasis in diabetics, and early reports showed dramatically increased perioperative morbidity and mortality for treatment of diabetics with acute cholecystitis. As a result, some authorities have recommended prophylactic cholecystectomy for diabetic patients with asymptomatic gallstones, which is in contrast to recommendations for nondiabetics. More recent investigators have shown comparable rates of operative morbidity and mortality for biliary surgery in diabetics when compared with the general population. Recent studies have questioned whether diabetes is an independent risk factor for gallstone formation. Decision analyses using these new data have shown that prophylactic cholecystectomy is not of clear benefit and should not be routinely recommended for diabetics with asymptomatic gallstones. We believe that available data, although limited, indicate that asymptomatic patients with diabetes do not benefit from screening for gallstones and that cholecystectomy should only be performed in cases of symptomatic cholelithiasis, as is the case in the general population. PMID- 8481074 TI - Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. AB - OBJECTIVE: To evaluate the relationship between serum cholesterol level and all cause, coronary heart disease (CHD), and non-CHD mortality as a function of age. METHODS: The data source was the biennial examination data from 1948 through 1980 for the 5209 men and women enrolled in the Framingham Heart Study. Age-specific analyses by the Cox proportional hazards regression model were performed of survival subsequent to ages 40, 50, 60, 70, and 80 years for all subjects enrolled and alive at each of the stated ages. Complementary models were studied that used high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or total cholesterol level as predictors of survival subsequent to the examination at which lipoprotein subfractions were determined (1968) through 1973). RESULTS: The relationship between total cholesterol level and all-cause mortality was positive (ie, higher cholesterol level associated with higher mortality) at age 40 years, negative at age 80 years, and negligible at ages 50 to 70 years. The relationship with CHD mortality was significantly positive at ages 40, 50, and 60 years but attenuated with age until the relationship was positive, but not significant, at age 70 years and negative, but not significant, at age 80 years. Results for the relationship between low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and mortality help explain these findings. Non-CHD mortality was significantly negatively related to cholesterol level for ages 50 years and above. The negative results in the oldest age group for all-cause and CHD morality appeared to be due to a negative relationship with low-density lipoprotein cholesterol levels rather than the protective effect of high high-density lipoprotein cholesterol levels. Similar results from several modified analyses make low cholesterol level due to severe illness an unlikely explanation for our results. CONCLUSIONS: Physicians should be cautious about initiating cholesterol-lowering treatment in men and women above 65 to 70 years of age. Only randomized clinical trials in older people can settle the debate over the efficacy and cost-effectiveness of lipid-lowering interventions for reducing mortality and morbidity in this population. PMID- 8481075 TI - Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV. AB - BACKGROUND: Inhibitors of hydroxymethylglutaryl co-enzyme A reductase are widely used to treat hypercholesterolemia. They have a good short- to medium-term safety profile, but long-term safety data are limited. METHODS: Seven hundred forty-five patients with severe hypercholesterolemia (mean baseline plasma cholesterol level on diet, 9.3 mmol/L [360 mg/dL]) were treated with lovastatin for a median duration of 5.2 years. Their mean age at baseline was 50 years, 68% were male, 60% had familial hypercholesterolemia, and 42% had a history of coronary heart disease. Seventy-seven percent of patients had titrations of lovastatin to 80 mg/d, and 58% took other lipid-lowering agents, usually bile acid sequestrants, concomitantly. RESULTS: The mean changes at 5 years in total, low-density lipoprotein, and high-density lipoprotein cholesterol were -35%, -44%, and +14%, respectively. Eighty percent of patients completed the study, 13% were unavailable for follow-up, 4% were discontinued due to adverse events unlikely to be related to lovastatin, and 3% (21) were discontinued because of drug attributable adverse events: marked but asymptomatic increase in aminotransferase values (10 patients), gastrointestinal disturbance (three patients), rash (two patients), myalgia (one patient), myopathy (two patients), arthralgia (one patient), insomnia (one patient), and weight gain (one patient). Sixteen patients died during the study, all of coronary disease. Of these, 14 had coronary heart disease at baseline. There were no deaths attributable to trauma, suicide, or homicide, and there were only 14 cases of cancer (vs 21 expected). There was no evidence for an adverse effect on the lens. CONCLUSIONS: Lovastatin is a generally well-tolerated and effective drug during long-term use. PMID- 8481076 TI - Excess body weight. An underrecognized contributor to high blood cholesterol levels in white American men. AB - BACKGROUND: The influence of body weight on serum lipids is often overlooked in clinical practice. METHODS: The association between body weight adjusted for height as calculated by body-mass index (BMI) and serum lipid and lipoprotein levels in white men was examined using the second National Health and Nutrition Examination Survey (NHANES II). Lipid results were categorized into six different levels of BMI: (1) 21.0 kg/m2 or lower, (2) 21.1 to 23.0 kg/m2, (3) 23.1 to 25.0 kg/m2, (4) 25.1 to 27.0 kg/m2, (5) 27.1 to 30.0 kg/m2, and (6) greater than 30.0 kg/m2, and three age groups: (1) young men (20 through 44 years), (2) middle-aged men (45 through 59 years), and (3) older men (60 through 74 years). RESULTS: Using linear trend analysis, changes in BMI from categories 2 to 5 in young men were associated with a total cholesterol level 0.59 mmol/L (23 mg/dL) higher (P < .01), a non-high-density lipoprotein (non-HDL) cholesterol level 0.70 mmol/L (27 mg/dL) higher (P < .01), and a low-density lipoprotein (LDL) cholesterol level 0.59 mmol/L (23 mg/dL) higher (P = .03). For middle-aged men and older men, the same change in BMI was associated with smaller but still significant differences in total cholesterol levels (higher by 0.31 mmol/L [12 mg/dL] [P < .01] and 0.28 mmol/L [11 mg/dL] [P < .01], respectively) and non-HDL cholesterol levels (higher by 0.37 mmol/L [14 mg/dL] [P < .01] and 0.25 mmol/L [10 mg/dL] [P < .01], respectively), whereas the LDL cholesterol levels were unchanged. Although advancing age may blunt the BMI-associated differences in total and LDL cholesterol levels, the BMI-associated differences in triglyceride levels (higher by 0.70 to 1.33 mmol/L [62 to 118 mg/dL] [P < .001]) and HDL cholesterol levels (lower by 0.18 to 0.39 mmol/L [7 to 15 mg/dL] [P < .001]) were of similar magnitude in all age groups. CONCLUSION: Excess body weight is associated with deleterious changes in the lipoprotein profile. Higher BMI was associated at all ages with higher plasma triglyceride level, lower HDL cholesterol level, and higher total and non-HDL cholesterol levels. In young men, the higher total cholesterol level was reflected mainly in the LDL cholesterol level; in middle aged and older men, in the non-HDL fraction. Programs to reduce coronary heart disease by improving lipid levels should include more emphasis on achieving and maintaining ideal body weight. PMID- 8481077 TI - Who should be screened for HIV infection? A cost-effectiveness analysis. AB - BACKGROUND: The advent of effective prophylactic treatments for asymptomatic persons infected with human immunodeficiency virus has led to interest in widespread screening programs. However, the costs of screening programs and therapy are high, and the prevalence of infection above which screening becomes an appropriate use of scarce health care dollars remains undetermined. METHODS: To examine the cost-effectiveness of screening in populations with differing prevalences of infection, we developed a Markov model to compare costs and life expectancy for two strategies: (1) screening and prophylactic treatment for infected persons who have or who develop low CD4+ (T4) cell counts, and (2) no screening. Based on studies in the literature, we estimated the prevalence of HIV infection, the rate of T4-cell loss, the rates of developing the acquired immunodeficiency syndrome and Pneumocystis pneumonia stratified by T4 cell counts, the life expectancy with the acquired immunodeficiency syndrome, the efficacy of prophylactic therapies, and costs. RESULTS: In populations with a prevalence of infection more than 5%, which includes known risk groups, screening costs less than $11,000 per life-year gained. In populations with a prevalence as low as 0.15%, screening costs only $29,000 per life-year gained. Even when the efficacy of zidovudine is assumed to be limited to 3 years, screening still costs less than $40,000 per life-year gained in populations with a prevalence of 0.5% or greater. However, in populations with a very low prevalence of infection (two to 10/100,000), such as members of the general population without reported risk factors, screening costs rise to between $290,000 and $1,277,400 per life-year gained. CONCLUSIONS: When considering only direct medical benefits, screening for asymptomatic human immunodeficiency virus infection in the general population, without regard to reported risk factors or seroprevalence data, would be expensive. In populations with a prevalence of infection of 0.5% or greater, however, the cost-effectiveness of screening falls within the range of currently accepted medical practices. These results suggest that screening be offered routinely to all persons in defined populations, such as persons receiving care at hospitals or clinics, or residing in geographic areas, where the seroprevalence is 0.5% or more, and underscore the need to conduct seroprevalence studies to identify such populations. PMID- 8481078 TI - Fluconazole-resistant Candida albicans after long-term suppressive therapy. AB - Candida albicans is generally considered to be susceptible, in vivo, to fluconazole. In the population infected with human immunodeficiency virus, recurrent bouts of oral and esophageal candidiasis have led to increasing use of fluconazole for long-term prophylaxis. With prolonged therapy, the issue of developing resistance emerges. We report a case of fluconazole-resistant C albicans esophagitis that developed after fluconazole was used for more than 600 days. PMID- 8481079 TI - Hypermagnesemic pseudocoma. AB - We treated a case of iatrogenic hypermagnesemia that clinically mimicked a central brain-stem herniation syndrome. Hypermagnesemia (magnesium level, 9.85 mmol/L [24 mg/dL]) can cause parasympathetic blockade, inducing fixed and dilated pupils, in addition to neuromuscular blockade. Extreme hypermagnesemia can therefore mimic a midbrain syndrome and cause a pseudocomatose state. PMID- 8481080 TI - Reversible parkinsonism induced by hypercalcemia and primary hyperparathyroidism. AB - We describe a patient who had the recent onset of both primary hyperparathyroidism and parkinsonism. Surgical removal of a parathyroid adenoma was followed by spontaneous resolution of the parkinsonism. Hypoparathyroidism and other disorders of calcium metabolism are recognized causes of secondary parkinsonism, while hyperparathyroidism is not. We review the relevant literature, which supports the hypothesis that hypercalcemia may have induced cytotoxic changes in the basal ganglia of this patient. PMID- 8481081 TI - Captopril and the effect of interferon gamma on monocytes. PMID- 8481082 TI - Nicotinic receptors in the cerebellar vermis modulate the gain of the vestibulospinal reflexes in decerebrate cats. AB - 1. The possibility that the cholinergic afferent system terminating in the vermal cortex of the cerebellar anterior lobe acts on the target neurons by utilizing nicotinic receptors has been investigated in decerebrate cats by testing the effects of local microinjection of cholinergic nicotinic agonists and antagonists on posture as well as on the dynamic characteristics of the vestibulospinal (VS) reflexes. 2. Unilateral injection into the vermal cortex of the culmen of nicotine (0.25 microliter at the concentration of 0.05-0.5 microgram/microliter saline) decreased the extensor tonus in the ipsilateral forelimb, while the extensor tonus in the contralateral forelimb increased. The some agent significantly increased the gain of the first harmonic component of the EMG responses of the ipsilateral and more prominently also of the contralateral triceps brachii to animal tilt. However, the phase angle of the responses remained bilaterally unmodified. The effects described above were first observed 5-10 min after the injection, reached the peak after 40-60 min and persisted for at least 2-3 h before disappearing. 3. The effective area was located between the second and the fourth folium of the cerebellar vermis rostral to the fissura prima, at the laterality of 1.4-1.8 mm. This area, which upon cathodal stimulation suppressed the spontaneous EMG activity of the ipsilateral triceps brachii, actually corresponds to the zone B of the cerebellar cortex which exerts a direct inhibitory influence on the lateral vestibular nucleus. Moreover, the effects were dose-dependent. 4. Microinjection of nicotinic antagonists of both the ganglionic type (hexamethonium, 0.25 microliter at 4 micrograms/microliters saline) and the neuromuscular type (d-tubocurarine, 0.25 microliter at 7 micrograms/microliters saline) produced a postural asymmetry opposite in sign to that elicited by nicotine. The same agents also decreased the response gain of the triceps brachii of both sides to animal tilt recorded either under normal conditions or after previous injections of nicotine. 5. The experiments indicate that the cholinergic system is involved in the control of posture as well as in the gain regulation of the VS reflexes. Previous histochemical studies had shown that the cholinergic fibers terminate not only on Purkinje (P)-cells, but also and more prominently as mossy fibers ending on granular cells. This system may thus affect the discharge of P-cells and related inhibitory interneurons not only ipsilaterally but also contralaterally to the side of the injection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481083 TI - EEG-blocking before and during voluntary movements: differences between the eyes closed and the eyes-open condition. AB - Movement-related EEG periods of 1 s duration were analyzed by fast Fourier transformation in the Bereitschaftspotential (BP) paradigm in 21 healthy, right handed normals. Spectra of the rest period and the BP period before the onset of the voluntary movement, and of the rest period and the movement period, were compared in order to describe blocking effects before and during movement execution (fast fist closure of the right hand). When comparing the rest period and the movement period with the eyes closed as well as with the eyes open, blocking was pronounced in both conditions within the total frequency range of the alpha-band, especially at positions contralateral to the movement over the motor cortex (C3') and the parietal cortex (P3) as well as at the parietal midline electrode (Pz). Moreover, when comparing the spectra of the rest and the BP periods in the eyes-closed condition, significant differences were again seen, with lower values during the BP period at C3' and P3. We were, however, able to observe over the parietal cortex an increase of alpha power in the 10 Hz range during the BP period with the eyes opened and fixated. This increase during the BP period in the eyes-open condition was not found when the eyes were closed. This paradoxical phenomenon of an increase of power with the eyes opened instead of blocking during the BP period, as observed in the eyes closed, may be due to an additional activation effect on the already activated (blocked) EEG in the eyes-open condition during fixation. PMID- 8481084 TI - Transient epileptiform experience affects the duration of penicillin-induced convulsive activity in the awake rat. AB - 1. Experiments were performed to investigate whether the sensitivity of the cerebral cortex to produce convulsive activity was modified by a transient epileptic focus. For this reason, 30 awake rats received two intracerebral penicillin (PCN) injections (125 IU/0.5 microliter solvent), the first one into the motor or visual cortex, the second one two weeks later into the motor cortex. Convulsive activity was recorded by means of EEG. 2. After the first PCN injection, interictal activity lasted 143.4 +/- 19.3, S.E. min (n = 17) in the motor cortex group, but 426 min (n = 13) in the visual group (p < 0.05). The median frequency of interictal potentials (np/min) was significantly lower in the motor cortex group than in the visual cortex group (18.4 and 25.5 np/min, respectively, p < 0.05). The period between the onset of the first and last seizure was 110.6 +/- 10.2 min for the motor cortex group, and 119.8 +/- 31.2 min for the visual cortex group. The seizures lasted longer and were less frequent in the motor than in the visual group (length: 12.5 +/- 1.1 vs 7.5 +/- 2.8 s; number: 43 +/- 11 vs 131 +/- 40, respectively, 0.05 < p < 0.1). 3. After the second PCN injection which was performed in all rats into the motor cortex, the duration but not the frequency of the interictal activity depended on the site of the first injection. The duration after this treatment was 96.8 +/- 43.3, S.E. min in the visual and 173.2 +/- 30.5 min in the motor cortex group (p < 0.05), while the frequency values of both groups were at a similar level (20.5 +/- 2.1 vs 18.9 +/- 1.7 np/min, respectively). Also the period with generalized activity after the second PCN injection was shorter in the visual than in the motor cortex group (43.9 +/- 32.3 vs 114.3 +/- 31.8 min, respectively, p < 0.05), and the number of seizures slightly lower (8 +/- 210 vs 54 +/- 30, respectively, p < 0.1). The length of the seizures was rather equal 11.6 +/- 2.5 vs 12.0 +/- 3.5 s, respectively, p > 0.1). 4. It is postulated that a transient epileptiform focus can induce, in a site-specific manner, long-lasting anticonvulsant effects. Therefore, epileptogenic experience may not only sensitize the brain, but also desensitize it with respect to the induction and duration of epileptiform activity. PMID- 8481085 TI - Histochemical assessment upon the striatal distribution of acetylcholinesterase in the cat. AB - The distribution of acetylcholinesterase (AChE) was explored in the striatum of the cat following a slightly modified Geneser-Jensen and Blackstad method. The well-known histochemical organization of the cat's striatum, characterized by the presence of small areas with poor concentration of AChE, called "striosomal bodies" or "striosomes", which were embedded in a prominent tissular matrix presenting more intense staining for AChE, was clearly recognized. An additional finding, however, was that regional variations in the deposit of AChE both in the striosomal bodies and in the matrix-compartment, occurred within different rostrocaudal and dorsoventral striatal territories of the cat's caudate nucleus. These results point to consider these two striatal compartments as part of a more complex histochemical design for the striatum of carnivores. PMID- 8481086 TI - The effect of pulvinar-lateral posterior complex stimulation on multiunit activity at the cingulate cortex in the cat. PMID- 8481087 TI - Early c-fos expression in the rat vestibular and olivocerebellar systems after unilateral labyrinthectomy. PMID- 8481088 TI - N5,N10-methenyltetrahydromethanopterin cyclohydrolase from the extremely thermophilic sulfate reducing Archaeoglobus fulgidus: comparison of its properties with those of the cyclohydrolase from the extremely thermophilic Methanopyrus kandleri. AB - Archaeoglobus fulgidus and Methanopyrus kandleri are both extremely thermophilic Archaea with a growth temperature optimum at 83 degrees C and 98 degrees C, respectively. Both Archaea contain an active N5,N10 methenyltetrahydromethanopterin cyclohydrolase. The enzyme from M. kandleri has recently been characterized. We describe here the purification and properties of the enzyme from A. fulgidus. The cyclohydrolase from A. fulgidus was purified 180 fold to apparent homogeneity and its properties were compared with those recently published for the cyclohydrolase from M. kandleri. The two cytoplasmic enzymes were found to have very similar molecular and catalytic properties. They differed, however, significantly with respect of the effect of K2HPO4 and of other salts on the activity and the stability. The cyclohydrolase from A. fulgidus required relatively high concentrations of K2HPO4 (1 M) for optimal thermostability at 90 degrees C but did not require salts for activity. Vice versa, the enzyme from M. kandleri was dependent on high K2HPO4 concentrations (1.5 M) for optimal activity but not for thermostability. Thus the activity and structural stability of the two thermophilic enzymes depend in a completely different way on the concentration of inorganic salts. The molecular basis for these differences are discussed. PMID- 8481089 TI - Formylmethanofuran: tetrahydromethanopterin formyltransferase and N5,N10 methylenetetrahydromethanopterin dehydrogenase from the sulfate-reducing Archaeoglobus fulgidus: similarities with the enzymes from methanogenic Archaea. AB - The sulfate-reducing Archaeoglobus fulgidus contains a number of enzymes previously thought to be unique for methanogenic Archaea. The purification and properties of two of these enzymes, of formylmethanofuran: tetrahydromethanopterin formyltransferase and of N5,N10 methylenetetrahydromethanopterin dehydrogenase (coenzyme F420 dependent) are described here. A comparison of the N-terminal amino acid sequences and of other molecular properties with those of the respective enzymes from three methanogenic Archaea revealed a high degree of similarity. PMID- 8481090 TI - Purification, partial characterization, and subcellular localization of a 38 kilodalton, calcium-regulated protein of Rhizobium fredii USDA208. AB - Calcium is essential for the growth of rhizobia and the formation of nitrogen fixing root-nodules on legumes, but its precise role in these processes remains unknown. We have found that Rhizobium fredii USDA208 accumulates a major 38 kDa protein when grown in media supplemented with 0.3-2 microM Cacl2. We have purified this protein and raised polyclonal antibodies against it. The protein initially is synthesized as a 40 kDa precursor which subsequently undergoes calcium-dependent processing to give rise to the mature polypeptide. Subcellular and immunocytochemical localization studies indicate that the 38 kDa protein accumulates preferentially in the periplasmic space. Its N-terminal sequence, AETIKIGVAGPMTG, shows significant homology to the N-termini of amino acid binding proteins from the periplasm, including leucine-, isoleucine-, and valine-specific binding proteins of Pseudomonas aeruginosa and Escherichia coli and a leucine specific binding protein of E. coli. The R. fredii protein does not, however, bind [3H]-leucine. The 38 kDa protein is encoded by the bacterial chromosome. It is absent in several rhizobia other than R. fredii, but antigenically related polypeptides are present in Escherichia coli and Erwinia carotovora subsp. carotovora. PMID- 8481091 TI - Characterisation of mutations in the Klebsiella pneumoniae nitrogen fixation regulatory gene nifL which impair oxygen regulation. AB - The nifL gene product of Klebsiella pneumoniae inhibits the activity of the positive activator protein NifA in response to increased levels either of fixed nitrogen or of oxygen in the medium. In order to demonstrate that the responses to these two effectors are discrete we have subjected nifL to hydroxylamine mutagenesis and isolated nifL mutants that are impaired in their ability to respond to oxygen but not to fixed nitrogen. Two such mutations were sequenced and shown to be single base pair changes located in different parts of nifL. The amino acid sequence of NifL shows limited homology to the histidine protein kinases which comprise the sensing component of bacterial two-component regulatory systems. In the light of the location of one of the oxygen-insensitive mutations (Leu294Phe) we have reassessed this homology and we suggest that the Gln273-Leu317 region of NifL may facilitate interactions between NifL and NifA. PMID- 8481092 TI - Isolation and characterization of a new spore-forming sulfate-reducing bacterium growing by complete oxidation of catechol. AB - A new mesophilic sulfate-reducing bacterium, strain Groll, was isolated from a benzoate enrichment culture inoculated with black mud from a freshwater ditch. The isolate was a spore-forming, rod-shaped, motile, gram-positive bacterium. This isolate was able of complete oxidation of several aromatic compounds including phenol, catechol, benzoate, p- and m-cresol, benzyl alcohol and vanillate. With hydrogen and carbon dioxide, formate or O-methylated aromatic compounds, autotrophic growth during sulfate reduction or homoacetogenesis was demonstrated. Lactate was not used as a substrate. SO4(2-), SO3(2-), and S2O3(2-) were utilized as electron acceptors. Although strain Groll originated from a freshwater habitat, salt concentrations of up to 30 g.l-1 were tolerated. The optimum temperature for growth was 35-37 degrees C. The G + C content of DNA was 42.1 mol%. This isolate is described as a new species of the genus Desulfotomaculum. PMID- 8481093 TI - [2,6-Epoxy-3-benzazocines: centrally acting N/O-acetals produced by cyclization of amino- and amidoacetals]. AB - Under acidic conditions the secondary amines 10a and 10b, the primary amine 15, the amide 17a, and the urethane 17b were cyclized to yield the 2,6-epoxy-3 benzazocines 11a, 11b, 16, 18a and 18b, respectively. Ring closure of the inverse amide 5a, however, failed to give the tricyclic N/O-acetal 6. With LiAlH4 the epoxy bridge of the urethane 18b was opened to afford the bicyclic 3-benzazocine 20. While the N-(2-methoxyethyl) derivative 11b did not influence the behaviour of mice, the N-methyl derivative 11a showed strong central effects. PMID- 8481094 TI - Nonsteroidal antiinflammatory agents, XVII: Inhibition of bovine cyclooxygenase and 5-lipoxygenase by N-alkyldiphenyl-pyrrolyl acetic and propionic acid derivatives. AB - A series of 19 N-alkyl-diarylpyrrolyl-acetic and-propionic acid derivatives was synthesized and tested. Using bovine blood as enzyme source the inhibition of cyclooxygenase and 5-lipoxygenase, respectively, was applied to determine the antiinflammatory activity. In general all compounds tested inhibit 5-lipoxygenase more effectively than cyclooxygenase. A structure-activity relationship is discussed. PMID- 8481095 TI - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XIX: 4,4'-Phenylene-bis-sydnone imines. AB - Fourteen 4,4'-m-phenylene- and two 4,4'-p-phenylene-bis-sydnone imine hydrochlorides have been synthesized. All compounds exhibited good solubility in water. In the m-series the 3-(3-phenylpropyl)-derivative 5c and the 3-hexyl compound 5l showed antiplatelet activities at or below 10 mumol/L (IC50, Born test with collagen). The corresponding p-compounds had the same (6l) or slightly lower (6c) activity. No effect on the fibrin formation (Quick-test) could be observed. PMID- 8481096 TI - [Benzomorphan analogs with doxpicomine partial structure: synthesis andpsychopharmacologic investigations of 5-aminomethyl- and 5-(alpha-aminobenzyl) substituted 2,6-epoxy-3-benzoxocines]. AB - Addition of the beta-alanine derivative 6 to the homophthalaldehyde monoacetal 5 and subsequent LiAlH4-reduction led to the dihydroxy acetal 8, which was cyclized with acid to give the 5-aminomethyl-2,6-epoxy-3-benzoxocines 2a and 2b. The reaction of 5 with the anion of the beta-lactam 9 yielded two separable diastereomers: 10a with u,l-configuration and 10b with 1,1-configuration. Via the 2-benzopyran 11a (11b), the aminoalcohol 12a (12b), and the secondary amine 13a (13b), the beta-lactam adduct 10a (10b) was transformed to give the 5-(alpha dimethylaminobenzyl)-2,6-epoxy-3-benzoxocine 3d (3b). The relative configurations of all these "beta-lactam route" products (10-13, 3d, and 3b) were established by their 1H-NMR-spectra. Attempts failed to get the missing diastereomers 3a and 3c by epimerization of the beta-lactams 11a and 11b or by reductive amination of the benzoyl derivatives 17a and 17b. Finally, 3a and 3c were obtained by phenylmagnesium bromide addition to the nitriles 21a and 21b, followed by LiAlH4 reduction, formaldehyde/NaBH3CN methylation and chromatographic separation. In the Irwin-screen (mouse) only 2a.HCl, 3b, and 3d (100 mg/kg body weight) caused weak central effects. PMID- 8481097 TI - Volatile metabolites in occupational exposure to organic sulfur compounds. AB - Dimethyl sulfide in breath was determined by the gas chromatographic method in 14 persons exposed to organic reduced sulfur compounds in sulfate pulp mills. Dimethyl sulfide concentrations in breath (range 0.04-0.69 cm3/m3 were compared to the combined workplace concentrations of methyl mercaptan, dimethyl sulfide and dimethyl disulfide. This method of analysis proved to be a practical noninvasive way to assess recent exposure, and therefore it should be applicable to workplaces contaminated with organic sulfur compounds in the pulp industry. PMID- 8481098 TI - Toluene metabolism in isolated rat hepatocytes: effects of in vivo pretreatment with acetone and phenobarbital. AB - Hepatocytes isolated from control, acetone- and phenobarbital-pretreated rats were used to study the metabolic conversion of toluene to benzyl alcohol, benzaldehyde, benzoic acid and hippuric acid at low (< 100 microM) and high (100 500 microM) toluene concentrations. The baseline formation rates of toluene metabolites (benzyl alcohol, benzoic acid and hippuric acid) were 2.9 +/- 1.7 and 10.0 +/- 2.3 nmol/mg cell protein/60 min at low and high toluene concentrations, respectively. In vivo pretreatment of rats with acetone and phenobarbital increased the formation of metabolites: at low toluene concentrations 3- and 5 fold, respectively; at high toluene concentrations no significant increase (acetone) and 8-fold increase (phenobarbital). Apparent inhibition by ethanol, 7 and 60 mM, was most prominent at low toluene concentrations: 63% and 69%, respectively, in control cells; 84% and 91% in acetone-pretreated cells, and 32% (not significant) and 51% in phenobarbital-pretreated cells. Ethanol also caused accumulation of benzyl alcohol. The apparent inhibition by isoniazid was similar to that of ethanol at low toluene concentrations. Control and acetone-pretreated cells were apparently resistant towards metyrapone; the decrease was 49% and 64% in phenobarbital-pretreated cells at low and high toluene concentrations, respectively. In these cells, the decrease in presence of combined ethanol and metyrapone was 95% (low toluene concentrations). 4-Methyl-pyrazole decreased metabolite formation extensively in all groups. Benzaldehyde was only found in the presence of an aldehyde dehydrogenase inhibitor. Increased ratio benzoic/hippuric acid was observed at high toluene concentrations. These results demonstrate that toluene oxidation may be studied by product formation in isolated hepatocytes. However, the influence of various enzymes in the overall metabolism could not be ascertained due to lack of inhibitor specificity. PMID- 8481099 TI - Surface binding and uptake of cadmium (Cd2+) by LLC-PK1 cells on permeable membrane supports. AB - Recent studies have shown that Cd2+ has relatively specific damaging effects on cell-cell junctions in the renal epithelial cell line, LLC-PK1. The objective of the present studies was to examine the surface binding and uptake of Cd2+ by LLC PK1 cells in relation to the disruption of cell-cell junctions. LLC-PK1 cells on Falcon Cell Culture Inserts were exposed to CdCl2 containing trace amounts of 109Cd2+ from either the apical or the basolateral compartments, and the accumulation of 109Cd2+ was monitored for up to 8 h. The integrity of cell-cell junctions was assessed by monitoring the transepithelial electrical resistance. The results showed that the cells accumulated 3-4 times more Cd2+ from the basolateral compartment than from the apical compartment. The accumulation of Cd2+ from the basolateral compartment occurred in two phases: a rapid, exponential phase that occurred in 1-2 h and coincided with a decrease in transepithelial resistance, and a slower, linear phase that continued for 6-8 h. The Cd2+ that accumulated during the rapid phase was easily removed by washing the cells in EGTA, indicating that most of it was bound to sites on the cell surface. By contrast, most of the Cd2+ that accumulated during the slower phase could not be removed by EGTA, indicating that it had been taken up by the cells. Additional studies showed that the rapid phase of Cd2+ accumulation was enhanced when Ca2+ was present at low concentrations (0.1 mM), and was greatly reduced when Ca2+ was present at high concentrations (10 mM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481100 TI - Electroretinographic assessment of early retinopathy in rats. AB - Amoscanate, a substance which damages photoreceptors, was administered orally to Wistar rats in doses of 10, 40, and 125 mg/kg body weight once daily for 3 or 10 days. At both times electroretinographic, ophthalmological, and histopathological examinations of the retina were carried out to compare the sensitivity of conventional methods and to test electroretinography (ERG) for suitability for use in toxicity studies. Time-dependent and dose-dependent effects were found by electroretinography and light microscopy. However, signs of retinal changes appeared earlier and more distinctly in the electroretinogram. Ophthalmological fundus examination in albino rats yielded no characteristic correlate. In conclusion, electroretinography constitutes a valuable supplement to histopathology and is suitable for use in toxicity studies. PMID- 8481101 TI - Effects of high doses of testosterone propionate and testosterone enanthate on rat seminiferous tubules--a stereological and cytological study. AB - The effects of exogenous testosterone on various testicular variables has become of increasing significance because of its potential use in male contraception. For this reason, high doses of two testosterone esters [testosterone propionate (TP) and testosterone enanthate (TE)] were used in a study of their influence on the morphology, length and curvature of the seminiferous tubules of the rat testis, and on cytological smears of the seminiferous tubules epithelium. TP was given for 14 days (3 mg/100 g body weight, i.m.) to assess the acute effects of testosterone on the seminiferous tubules. TE was administered for 60 days (in the same manner as TP) to study possible chronic effects on the rat testis. After TP and TE treatment the seminiferous tubule epithelium showed disorganization and desquamation of spermatogenic cells. In the TP-treated testes the tubules lined with Sertoli cells only were observed. The values for the length and curvature of seminiferous tubules of the TP- and TE-treated rats were significantly reduced (p < 0.001). All these changes were observed earlier in the TP-treated than in the TE-treated animals. In cytological smears of the testis of the TP- and TE-treated rats an increase of vacuoles and residual bodies in Sertoli cell cytoplasm was noted. In addition, a reduction of spermatogenic cells, particularly sperms, was manifest in the smears after treatment. Large groups of Sertoli cells were seen in the smears from these testes. PMID- 8481102 TI - Investigation of possible metabolism of pigment yellow 17, a 3,3' dichlorobenzidine-based pigment, after inhalation exposure in rats. AB - Rats were exposed by inhalation to the technically highest administrable concentration of 230 mg Pigment Yellow 17/m3 air for 4 h. Inhalability of the dust was guaranteed by a mass-median aerodynamic diameter of 1.0-1.1 microns. For 14 days after exposure, urine and serum samples were analysed for 3,3' dichlorobenzidine, the parent carcinogenic amine of the test compound. No 3,3' dichlorobenzidine could be detected either in urine or blood, the detection limit being 5 ng/ml for both media. Based on the results of this study there is no evidence for metabolic cleavage of Pigment Yellow 17 to 3,3'-dichlorobenzidine in the rat. PMID- 8481103 TI - Effect of Sairei-to on gentamicin nephrotoxicity in rats. AB - The effect of Sairei-to, an oriental traditional medicine, against gentamicin nephrotoxicity was examined in gentamicin nephrotoxicity rat models. Gentamicin nephrotoxicity was induced by s.c. injection of gentamicin (100 mg/kg/day, for 3 days) in male Sprague-Dawley rats. Renal functions of two rat groups were compared, one eating rat chow containing 2.5% Sairei-to, the other eating normal rat chow. Sairei-to administration reduced the increase of urinary N-acetyl-beta D-glucosaminidase (NAG) and protein excretion, and decreased creatinine clearance induced by gentamicin. Gentamicin increased renal cortical malondialdehyde (MDA) concentration in normal diet group but not in the Sairei-to diet group. The renal cortical gentamicin concentration was not different between the two groups. In conclusion, Sairei-to shows reno-protective action against gentamicin nephrotoxicity, possibly through its anti-oxidant action. PMID- 8481104 TI - Poisoning by toxic honey in Turkey. AB - One of the food intoxications encountered in Turkey is the case caused by toxic honey made by bees from Rhododendron species. R. luteum and R. ponticum are the two species which grow in the north regions of Turkey. Grayanotoxins, mainly Grayanotoxin I (Andromedotoxin) occurring only in Ericaceae plants, are the compounds responsible for poisoning. In this investigation, the diagnosis and treatment of 11 cases of poisoning admitted to Kartal Occupational Diseases Hospital between 1983 and 1988 are presented. The results of the light microscopic and chemical analysis of toxic honey samples are compared with those of the ordinary honey samples and the extract of Rhododendron leaves. PMID- 8481106 TI - In vitro percutaneous absorption and metabolism in man of 2-chloro-4-ethylamino-6 isopropylamine-s-triazine (atrazine). AB - Atrazine is an extensively used herbicide in the USA. Our objective was to determine the absorption and metabolism (detoxification) of atrazine in human skin. Percutaneous absorption of atrazine in human skin from four sources was examined utilizing a flow-through in-vitro diffusion system. About 16.4% of the applied dose was absorbed by the skin. Radioactivity in the receptor fluid at 20 h was less than 5% of the administered dose. The highest concentration of the applied dose was found in the skin supernates, where 12.0% of the dose (68 nmol) was recovered. Some metabolites of atrazine were identified by thin layer and high pressure liquid chromatography after extraction of receptor fluid and the skin supernates. Two metabolites of atrazine [2-chloro-4-ethylamino-6-amino-s triazine (desisopropylatrazine) and 2-chloro-4,6-diamino-s-triazine] were found in the receptor fluid and the skin supernates. An additional metabolite (2-chloro 4-amino-6-isopropylamino-s-triazine) was found in the skin supernates. Since desisopropylatrazine represented about 50% of the total metabolites formed during percutaneous absorption, cleavage of the N-isopropyl to the amino product was a key step in the metabolism of atrazine. Further metabolism may proceed by cleavage of the N-deethyl group to give totally dealkylated atrazine. The biotransformation of atrazine was studied in skin microsomal fraction supplemented with an NADPH-generating system. In analogy to metabolism during percutaneous absorption, atrazine was metabolized to its deisopropyl and deethylpropyl derivatives. In addition, 2-hydroxy derivatives of atrazine were formed by the skin microsomal fractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481105 TI - Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate. AB - We measured in nine patients, poisoned by organophosphorus agents (ethyl parathion, ethyl and methyl parathion, dimethoate, or bromophos), erythrocyte and serum cholinesterase activities, and plasma concentrations of the organophosphorus agent. These patients were treated with pralidoxime methylsulphate (Contrathion), administered as a bolus injection of 4.42 mg.kg-1 followed by a continuous infusion of 2.14 mg.kg-1/h, a dose regimen calculated to obtain the presumed "therapeutic" plasma level of 4 mg.l-1, or by a multiple of this infusion rate. Oxime plasma concentrations were also measured. The organophosphorus agent was still detectable in some patients after several days or weeks. In the patients with ethyl and methyl several days or weeks. In the patients with ethyl and methyl parathion poisoning, enzyme reactivation could be obtained in some at oxime concentrations as low as 2.88 mg.l-1; in others, however, oxime concentrations as high as 14.6 mg.l-1 remained without effect. The therapeutic effect of the oxime seemed to depend on the plasma concentrations of ethyl and methyl parathion, enzyme reactivation being absent as long as these concentrations remained above 30 micrograms.l-1. The bromophos poisoning was rather mild, cholinesterases were moderately inhibited and increased under oxime therapy. The omethoate inhibited enzyme could not be reactivated. PMID- 8481107 TI - Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver. AB - The hamster is known to display very high rates of monooxygenase-mediated biotransformation. In comparison with other species little knowledge has been gathered with respect to the nature of its cytochrome P450 enzymes and their respective inducibility. We studied the consequences of induction of P450 enzymes in rats and Syrian golden hamsters using the regioselective oxidative O demethylation of the coumarin derivative scoparone. This metabolic conversion indicates differential effects of P450 inducers in the rat, in which various types of inducers cause different shifts in the isoscopoletin/scopoletin metabolite ratio (I/S-ratio). Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats. In rat liver microsomes total demethylation rates of scoparone increased upon in vivo treatment with phenobarbital or beta-naphthoflavone. Phenobarbital reduced the I/S-ratio whereas beta-naphthoflavone caused an increase in this ratio. In hamster liver microsomes both phenobarbital and beta naphthoflavone treatments resulted in a decrease in the I/S ratio. In this species the total scoparone demethylation rate was not much affected by phenobarbital, but beta-naphthoflavone caused a huge increase in over-all scoparone biotransformation. In both species, dexamethasone, isoniazid and clofibrate were much less effective. In contrast to the rat, in the hamster the scoparone biotransformation profile cannot be used to differentiate between phenobarbital- or beta-naphthoflavone-treated animals. PMID- 8481109 TI - The disturbed mind. PMID- 8481108 TI - Enzyme induction of the early chick embryo by airborne particulate extracts. AB - The induction by airborne particulate extracts of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (ECOD) in early chick embryos was studied to determine whether or not lethality by the extracts was related to the induction. The optimal pH values for AHH and ECOD were 7.1 and 6.9, respectively, after administering the extracts to early embryos. The AHH inducing capacity was significantly increased 4 h after injection of the extracts, then the value gradually increased. The ECOD inducing ability was similar to that of AHH, although to a lesser extent. Among fractions from the extracts, the neutral fraction was responsible for most of the AHH inducing activity. Two neutral subfractions (N2 and N3), consisting mostly of polycyclic aromatic hydrocarbons (PAH) and their derivatives, had the highest inducing activity. A dose-response relationship was observed between the amounts of the N2 and induction of AHH and ECOD in 8-day-old embryos. When the N2 was administered at different stages of development (days 5-9), the values of induced AHH and ECOD activities increased along with the days of development. Extracts of the smaller airborne particulates (< 1.1 and 1.1-2.0 microns cut-off diameters) had stronger AHH and ECOD inducing abilities than those of the larger, since the former contained high levels of PAH and their derivatives. These results suggested that PAH and their derivatives in the airborne particulates induced AHH and ECOD activities in the early chick embryo. The relationship between the extent of AHH and ECOD inducing activities and that of embryolethality caused by extracts of airborne particulates was not well established. PMID- 8481110 TI - Compliant victims of the sexual sadist. AB - This is a descriptive summary of the experiences of a sample of women who have been consensually involved with criminal sexual sadists. The paper details the physical, sexual, and psychological abuse to which the women were subject as well as the process by which they were transformed from independent, competent women to the compliant appendages of their criminally active partners. Similarities in the sexual sadist's criminal and consensual sexual activities as they reflect a specific paraphilic preference are discussed. PMID- 8481111 TI - Obsessive compulsive disorder. An update. AB - Developments in the neurosciences, neuropharmacology and in cognitive/behavioural therapy have helped in providing effective treatment for OCD. That OCD can be treated successfully is likely to lead to greater public demands on clinicians for diagnosis and treatment. It is thus hoped that the quality of life for sufferers will improve and the secretiveness and shame they now feel about their illness will no longer occur. PMID- 8481112 TI - Assessing the risk of violent and fear-inducing behaviour in the mentally disordered. AB - Assessing the risks of violence in mentally disordered individuals is, as with suicide risk, an uncertain process that tends to produce high numbers of false positives, as well as the occasional failure to recognise imminent danger. Ideally we should have a data base on which actuarial estimates could be made, but in our present state of knowledge careful clinical assessment and common sense have to suffice. When the result of assessing a patient as at risk of being violent is to increase the level of support and therapeutic activity provided few ethical issues arise. When involuntary hospitalisation or curtailment of rights follows, the assessment of dangerousness must be soundly based and persuasive. The assessment of dangerousness remains a dubious business but on occasion it is our business. PMID- 8481113 TI - Identifying potential gun offenders. AB - According to the results of a Saulwick Age Poll (The Age, 13 June 1988) one in three Australians aged 18 to 24 would like to have a gun. Many of them join pistol shooting clubs. Target pistol shooting, part of the Olympic Games programme, is a safe sport. It develops self discipline, teaches body control, to make decisions under pressure, how to handle stress and think logically as an individual. There are about 70 pistol clubs in Victoria. Following the rule "prevention is better than the cure" MISC introduced screening of new members. The system--interview, the questionnaire, a probation period--was found during the two year trial period successful as a strategy to identify people who are potential risks to society. PMID- 8481114 TI - Challenges to the admissibility of DNA profiling evidence in criminal trials. AB - This article presents an overview of the credibility of DNA profiling in criminal trials. DNA profiling does not provide absolute identification but has to be considered as a component of evidence. Apart from being used to help determine guilt it can be used to exonerate suspects. PMID- 8481115 TI - Youth suicide in the Australian Capital Territory. AB - A study was made of all suicides of young people aged under 25 years in the Australian Capital Territory (ACT) over the 6 year period 1985 to 1990. The rationale was to attempt to identify significant risk factors. 'Psychological autopsies' were carried out on material from the coroner's files. The results of the study suggest that suicide among the young in the ACT appears to be the result of a complex interplay of intrapersonal, interpersonal and social environmental factors. PMID- 8481116 TI - Criminal investigative analysis. AB - In its pursuit of those responsible for the commission of serious violent crime, law enforcement will continue to explore and refine the Criminal Investigative Analysis process. To this end, it will enthusiastically collaborate with the medical profession. The results of continuing studies will be made available to relevant bodies. If a general practitioner becomes aware of a patient's unexplained changes of behaviour an additional question should perhaps be considered: "What else is happening in your life?" The response and its evaluation and subsequent intervention may avert a tragedy. Notification of police and anonymity of a practitioner are always contentious issues. In my mind, responsibility to the community in general completely over-shadows the debate on anonymity and confidentiality. In recent discussions with professionals involved in the mental health field there was a consensus that if a treating doctor becomes aware that a person is likely to be violent or cause harm to themselves or the community, the problem of confidentiality does not occur. The safety of the public is paramount. In addition, senior vice president of the Australian Medical Association, Dr Brendan Nelson, was quoted in the Sunday Age 16 August 1992 as follows: "If a patient tells you that she is going to kill her husband and you believe it is a serious threat, then you have a responsibility to the person whose life is in danger to inform the authorities." To do otherwise, surely is an injustice and it would appear to therefore follow, also unethical and immoral.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481117 TI - An unlikely pregnancy and its consequences. AB - This commentary illustrates the case of a young married woman (who will be referred to as Debbie), who presented requesting a tubal ligation, but after a joint discussion with her husband (who will be referred to as Boyd), it was decided that he would have a vasectomy. Shortly after the operation, Debbie became pregnant. The importance of full discussion of medical procedures with patients and their families so that informed decisions can be made and a close working relationship established will be highlighted. PMID- 8481118 TI - Euthanasia in The Netherlands. General practice facts. AB - The recent survey of the way general practitioners act in case of euthanasia, did point to the fact that procedural requirements were not always observed. This concerned particularly the issuing of an appropriate death certificate. It is important that the practice of euthanasia be prudently surveyed in order to safeguard the standard of euthanasia that general practitioners are able to provide. Fear in the community for unwanted medical practice is understandable when the history of Hitler Germany is used as a frame of reference. Stories of mercy killing in nursing homes or elsewhere will as well increase anxiety. This fear is, however, based on a wrong understanding of euthanasia. The formulated requirements and prudent surveillance offer the best protection against the fear of the community. PMID- 8481119 TI - Rehabilitation of elderly patients. Don't give up too quickly! AB - Rehabilitation means 'to restore to previous condition, rights, privileges, to attain some degree of independence (New Oxford Dictionary). The general practitioner will inevitably be involved in deciding when and where the patient will go. With increasing care, understanding and effort, it is hoped that with the above in mind, an increasing number of seemingly incapable elderly people will be helped. Just as with other age groups, an increasing number of elderly will be able to continue making a worthwhile contribution to society and to solve their own problems in ways that they choose. PMID- 8481120 TI - Epilepsy and sport. AB - Sport and epilepsy are not mutually exclusive, providing the disease has been properly diagnosed and managed and adequate safeguards are taken. The author also outlines specific contraindications for the sports-minded person with epilepsy. PMID- 8481122 TI - Curing the warts. PMID- 8481121 TI - The health information network. AB - The health information network concept is certainly visionary. It has much merit but it is doomed to failure unless the proposed users of this information show much more concern for confidentiality. PMID- 8481123 TI - Update in the treatment of schizophrenia. AB - The large number of drugs available to treat schizophrenia and the emergence of atypical and newer agents that provide efficiency with lessening of side effects may not only serve to provide more amelioration against this disease, but may also help us to unravel the neurochemical defects of the disorder. Despite these encouraging trends, the reality is that schizophrenia is still a devastating illness for a sizeable minority affected with the condition, that a 'cure' is not yet possible, and that drug therapies alone will not provide all that is required in acute or continuing management. Supporting care in the community for patient and family are just as important as pharmacotherapy in managing this problem. PMID- 8481124 TI - Intellectual disability. The counselling of parents and family. AB - A sympathetic general practitioners who is aware of the problems encountered by these families has a vital role in their health care. Families who face a lifetime of dealing with a myriad of problems appreciate having an accessible counsellor they are comfortable with. Being aware of the process of adaptation undergone by the family enables practitioners to do their job more effectively. Disability and its effect on the family is a worthwhile challenge for holistic family practitioners. PMID- 8481125 TI - Patient education. Tubal ligation. PMID- 8481126 TI - Dr David Hollands. Wildlife photographer. AB - Dr David Hollands and his wife, Dr Margaret Hollands, have been a successful team -in their professional and family lives. Their working lives and private lives have obviously been closely enmeshed and it is difficult to attribute the success of one in a particular field to one only--somewhere along the line there has been the influence and more often than not the direct help of the other. Country medical practice has provided David Hollands with a deeply satisfying professional life and allowed him to develop his boyhood love of natural history. Although well known in his own locale of Orbost, Victoria, for his medical skill he has recently gained wider recognition as a wildlife photographer with the publication of his two books. His wife, Margaret, will be the subject of next month's Notable Australian Doctors. PMID- 8481127 TI - Split skin injuries. PMID- 8481128 TI - Marital surprises. PMID- 8481129 TI - Extemporaneous prescribing. Module. 1. AB - Australian Family Physician is pleased to be able to present a home course in extemporaneous prescribing, an interesting area that is poorly understood by many practitioners, especially recent graduates. Dr Bernard Kelly has been teaching this discipline to Family Medicine Trainees in New South Wales for many years and has written a series of modules to be placed in the journal during 1993. A question of historical pharmacological interest is included at the end of each module. PMID- 8481130 TI - True stories. AB - Four stories, all true, all upsetting, all with lessons for the discerning doctor. In this series, life won 3-1. But none of us are immortal, no matter what an over confident American group who call themselves 'The Immortals' I saw on television the other day has to say. Lest we forget--families, friends, patients and what we do to them, stress and risk factors--the potpourri of our medical lives. PMID- 8481131 TI - Chronic fatigue syndrome. PMID- 8481132 TI - GPs--the missing link. PMID- 8481133 TI - Concomitant coronary revascularization and resection of lung cancer. AB - As age and smoking are common risk factors, patients with lung cancer frequently have coexistent ischaemic heart disease. Ignoring the coronary disease results in an unacceptable operative mortality, whilst sequential coronary grafting and lung resection may prejudice the results of the resection. A series of 10 patients underwent combined coronary revascularization (average 2.9 grafts per patient) and lung resection for carcinoma (seven lobectomies, one bilobectomy, one sleeve lobectomy, and one pneumonectomy). The majority of patients had unstable angina, triple vessel or left main coronary artery stenosis and poorly staged tumours. There was no operative mortality and the average hospital stay was 20 days. Half the patients had significant peri-operative morbidity; seven are alive and well at between 12 and 38 months follow-up; but three have died of recurrent carcinoma (one with associated sepsis) at 3, 8, and 13 months. Combined coronary revascularization and lung resection can be safely performed in selected patients. The early morbidity is mainly related to the cardiac procedure and impaired respiratory function preoperatively, but the long-term results are dependent upon the control of the lung carcinoma. PMID- 8481134 TI - Hip fractures: changing patterns in hospital bed use in NSW between 1979 and 1990. AB - Osteoporotic hip fractures are associated with significant medical, social and financial costs. To examine trends in hip fracture incidence, acute hospital admissions, bed use and outcome for these fractures were reviewed for the period 1979-90. In this period, there was a 45% increase in the total number of fractures. In women aged 65 and over increases in admission rate were found between 1979 and 1986. Fracture admission rates for women stabilized after 1986, but remained approximately 7% higher than in the baseline year of 1979. In men aged 65 years and over there was no discernible change in fracture incidence. Length of stay in hospital was inversely related to the total number of proximal femoral fracture cases in each year. As a result of the large decreases in length of stay, overall bed use in 1991 was very similar to that in 1979, in spite of the large increase in fracture admissions. This reduction in length of stay may reflect, not only the pressures of greater demand, but also improved surgical and postoperative management and the effects of early intervention and rapid transit treatments. PMID- 8481135 TI - The cost-efficiency of incentive spirometry after abdominal surgery. AB - This report gives the results of a cost-efficiency analysis of a prospective longitudinal study evaluating two forms of prophylaxis against postoperative pulmonary complications in 876 patients undergoing abdominal surgery. It cost $12.19 per patient for conventional chest physiotherapy, and equivalent costs accrue when incentive spirometers are recycled and used on average 2.3 times (in the Royal Perth Hospital, incentive spirometers are recycled an average of 4.7 times). Maximum cost-containment can be achieved by carefully selecting patients for physical chest care and then instigating a programme of perioperative chest care utilizing recycled incentive spirometers. This approach does not compromise the clinical benefits of prophylactic chest care and allows physiotherapy resources to be directed toward patients with established pulmonary problems. PMID- 8481136 TI - Jejunal diverticulosis. AB - Jejunal diverticulosis is considered to be a generally asymptomatic condition in which the diverticula are pulsion mucosal herniations with walls lacking a muscle layer. These opinions in particular are examined in this review of 20 cases of jejunal diverticulosis treated during an 8 year period. The predominant complication in each case was inflammation or perforation (nine), diarrhoea or malabsorption (five), haemorrhage (three), chronic abdominal pain (two) and pseudo-obstruction (one). At least 10 patients had more than one complication, although this was often unrecognized. Ten patients complained of chronic abdominal pain, in eight of whom the cause was not diagnosed until other complications supervened. Unrecognized malabsorption may be common, as the mean serum albumin in 12 patients presenting acutely with inflammation, perforation or haemorrhage, was low (mean 32 g/L, normal 39-48 g/L). Histology sections were reviewed in the 12 cases that underwent resection, of whom 11 were suitable for classification. Four cases had narrow-mouthed pulsion diverticula with a thin or absent muscle coat, and had developed at the point of blood vessel penetration. Four cases had wide-mouthed diverticula in which the muscle layer was present, suggesting an abnormality of the intestinal wall. Two had features of both. In one case a Meckel's type diverticulum was located 10 cm from the duodenal-jejunal flexure. Seven had mucosal villous atrophy consistent with bacterial overgrowth. In conclusion, jejunal diverticulosis may be associated with complications more frequently than has been recognized and pathologically is a diverse condition. PMID- 8481137 TI - The safety and duration of non-operative treatment for adhesive small bowel obstruction. AB - Small bowel obstruction (SBO) due to adhesions is often initially treated non operatively but the safety and duration of non-operative treatment is controversial. The aims of this study were to assess the safety of non-operative treatment and determine the optimal duration of non-operative treatment in adhesive SBO. A retrospective analysis of patients admitted with a diagnosis of adhesive SBO following an initial period of non-operative treatment was performed. Patients whose condition resolved with non-operative treatment were compared with patients who required surgical intervention after an initial period of non-operative treatment. There were 123 admissions having an initial period of non-operative treatment. The SBO resolved in 85, the remaining 38 required surgical intervention. Complete resolution occurred within 48 h in 75 (88%) cases, the remaining 10 had resolved by 72 h. Thirty-one of 38 patients required surgical intervention for SBO more than 48 h duration after admission. The difference between cases resolving within 48 h and those requiring surgery after 48 h was significant (chi 2 = 113, P < 0.001). Three (2.4%) patients, initially treated non-operatively, had small bowel strangulation. All three were operated on within 24 h of admission when changes in clinical findings suggested small bowel strangulation may be present. There were no deaths in the group having an initial period of non-operative treatment. In the absence of any signs of strangulation, patients with an adhesive SBO can be managed safely with non operative treatment. Most cases of adhesive SBO that will resolve, do so within 48 h of admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481138 TI - Laparoscopic management of pneumatic dilatation resistant achalasia. AB - Three patients with achalasia, who were successfully managed by laparoscopic Heller myotomy and Nissen fundoplication, are described. Each patient had failed to respond to two pneumatic dilatations of the oesophagus. PMID- 8481139 TI - Mid-colon oesophagocoloplasty for corrosive oesophageal strictures. AB - Corrosive strictures of the oesophagus are common and being long and dense frequently require surgical replacement of the oesophagus. Presently available techniques of oesophagocoloplasty are associated with a significant mortality and major morbidity, such as a high rate of ischaemic necrosis of the colon, cervical salivary fistula or oesophagocolic stenosis. A method of mid-colon oesophagocoloplasty using an isoperistaltic colonic segment from the mid ascending to the mid-descending colon is reported. The procedure was carried out in 33 patients. The conduit was placed retrosternally in 27 patients and subcutaneously in the rest. The essential steps of the procedure are simultaneous neck and abdominal dissection, near-total mobilization of the colon from the ileocaecal segment to the sigmoid colon and sequential clamping of ileocolic, right colic and usually the middle colic vessels leaving the left colic vessels as the major vascular pedicle. The divided ileum is used to pull the colon into position thus avoiding traumatization of the colon and leaving the whole length of the mobilized colon available for anastomosis. A wide side to side oesophagocolic anastomosis in the neck, resection and discarding of the bulky terminal ileocaecal segment after completion of the cervical anastomosis, closure of the terminal end of the colon and its placement adjacent to the hypopharynx and end to side cologastric anastomosis complete the procedure. There was no mortality and there was no instance of colonic necrosis. The procedure restored an ability to eat normal food in 93.9% of patients compared to only 39.2% of patients with bougienage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481140 TI - Angular vein of the axilla and the anatomy of the subscapular vein important in axillary node dissection. AB - The anatomy of the subscapular vein and its tributaries is described. Importantly, the angular branch of the subscapular vein and its almost constant relationship to the thoracodorsal nerve were demonstrated. PMID- 8481141 TI - Videothoracoscopic primary repair of early distal oesophageal perforation. AB - Distal oesophageal perforation following dilation of oesophageal strictures or achalasia is usually recognized soon after the event. Treatment of two patients with perforation resulting from vigorous achalasia, diagnosed within hours of the procedure, was approached by videothoracoscopic exposure and successful primary repair was achieved in both instances. Details relating to patient preparation and operative technique are presented. Both patients recovered, with normal diet being tolerated by the seventh day after surgery, were discharged on day eight and 10 and returned to normal activities within 3 weeks of surgery. The technique presented is apparently well suited to distal oesophageal perforations diagnosed early, when primary closure can be achieved safely, and significantly improves patient recovery after this often iatrogenic injury. PMID- 8481142 TI - Use of Blount's epiphyseal staples to control massive iliac venous haemorrhage. AB - Significant injuries to major veins are life-threatening events and may lead to patient exsanguination. Treatment usually consists of direct suture repair. A case in which a serious iliac venous haemorrhage was not able to be controlled with the usual surgical procedures is reported. A desperate attempt to achieve haemostasis using orthopaedic staples was successful. The simplicity of this technique makes it a useful addition to the surgeon's armamentarium when dealing with life-threatening venous haemorrhage. PMID- 8481143 TI - Branch duct origin of solid type pancreatic ductal carcinoma. AB - A case of branch duct origin of solid type pancreatic ductal carcinoma is presented. Stepwise tissue sections of an entire specimen, including the carcinoma area, and mapping, with special reference to the relationship between the main duct and the carcinoma area, were performed. Carcinoma cells of the branch duct showed intraductal spread with minimal stromal invasion. No carcinoma tissue was observed in the main duct. Therefore this case was considered to be of branch duct origin. The finding of histologically identified branch duct origin of solid type pancreatic ductal carcinoma indicates a distinct advantage to be gained by giving special attention to both the main and branch ducts when using image diagnosis for early detection of carcinomas, and may represent the first reported surgically resected case. PMID- 8481144 TI - Metastasis of pineal germinoma via ventriculoperitoneal shunt. AB - The case of a 13 year old boy with pineal germinoma and subsequent metastasis 3 years later via ventriculoperitoneal shunt to the abdominal cavity is presented. The abdominal disease was managed with chemotherapy and subsequent surgical resection. He remains free of disease 2 years following the resection. The literature regarding this rare complication is reviewed. PMID- 8481145 TI - Naevoid basal cell carcinoma (Gorlin's) syndrome. AB - The multiple naevoid basal cell carcinoma syndrome (Gorlin's syndrome) is an inherited multisystem disorder which affects not only the skin, but also the skeletal system and a variety of other tissues and organs. This is a report of the case of a 29 year old woman who presented with multiple advanced basal cell carcinomas. On the basis of a literature review, guidelines for management are suggested and the importance of early diagnosis and regular follow-up is emphasized. PMID- 8481146 TI - Gallstone ileus complicating endoscopic sphincterotomy. AB - A case of gallstone ileus is described complicating an endoscopic sphincterotomy. This rare cause of small bowel obstruction should be considered following endoscopic treatment of very large bile-duct calculi. PMID- 8481147 TI - Delayed cerebrospinal rhinorrhoea. PMID- 8481148 TI - Helicobacter pylori. PMID- 8481149 TI - Some fallacies of statistical inferences about psychotherapy. AB - Statistical methodology does not provide an effective, impartial, or objective way to determine the validity of theories of psychotherapy. Furthermore, the correlations revealed by statistical studies of psychotherapy are clinically irrelevant. Nevertheless there is a growing trend to recognise only statistically "proven" techniques of psychotherapy as legitimate medical treatment. The replacement of established medical standards for psychotherapy with this bogus new scientism is likely to lead to iniquitous clinical and administrative restrictions upon psychotherapists which will cause unnecessary suffering to patients. PMID- 8481150 TI - Adolescent identity disorder: a case presenting with cultural identification problem. AB - A computer search of the psychiatric literature starting from 1983 showed no studies or clinical reports of Identity Disorder. A case history of a 15 year old Chinese boy with Identity Disorder presenting with cultural identification problems is described. Cultural identification among second generation immigrants is discussed in detail. Cultural factors can be very important in the consideration of Identity Crisis and Identity Disorder in adolescents. PMID- 8481151 TI - Making conscious identifications: a means of promoting empathic contact. AB - A rationale for encouraging the development of empathic skills is discussed, along with the current status of such training in medical education. The concept of empathy and previous approaches to empathy training are discussed briefly. A technique, which I have called "conscious identification", is described. In essence it involves an attempt by the trainee to "put himself in the patient's position" and to write an account in the first person of what he perceives of the patient's experience. The technique is illustrated using three case studies. Possible applications are discussed as well as the limitations of the technique. PMID- 8481152 TI - Psychotherapy supervision in Hong Kong: a meeting of two cultures. AB - The experience of psychotherapy supervision of a group of trainee psychiatrists, in a university setting in Hong Kong, is reported from the supervisor's perspective. The trainees showed difficulties in this exercise. The cultural difference between the supervisor and the trainees, and that between the Western psychotherapy culture and the Chinese culture, is discussed. It is then followed by a description of what is seen as the trainees' resistance in the acceptance of psychotherapy and of the supervisor. This is considered to be one of the problems in the transcultural application of psychotherapy, and has to be overcome if this importation is to be successful. PMID- 8481153 TI - Psychiatrist-patient sexual relationships: the ethical dilemmas. AB - Sexual relationships between psychiatrists and their patients raise a number of important ethical issues. The power inequality, transference and dependence which often occur in a therapeutic relationship render patients vulnerable to exploitation. Psychiatrists informed by a patient of sexual contact with a previous psychiatrist face a complex ethical dilemma. Attempts at regulation by professional organisations, or by the legal system, may create conflicts between the rights of the persons involved. The role of the psychiatric profession in confronting the problem of sexual exploitation of patients is discussed. PMID- 8481154 TI - Back to bedlam? Chelmsford and the press. AB - The Australian press played a vital part in bringing the events at Chelmsford Private Hospital to the attention of the general public, and in pressuring the New South Wales government to institute a Royal Commission into Deep Sleep Therapy. This paper describes the ways in which the press brought Chelmsford events onto the public agenda. It pays particular attention to aspects of the press coverage of the findings of the Royal Commission. The paper identifies the discourses concerning psychiatric care, the doctor-patient relationship and the role of the government in regulating the medical profession which were dominant in press accounts of Chelmsford. It is argued that while pre-existing stereotypes about mad psychiatrists and asylums were used to describe Chelmsford, more confronting ideas concerning the need for medical regulation and patient consumerism received press attention and therefore a public airing. The implications for psychiatric care in Australia are examined. PMID- 8481155 TI - The snake on the caduceus: dimensions of medical and psychiatric responsibility in the Third Reich. AB - The literature on the activities of medical professionals during the tumultuous years of the Third Reich has, over the last decade, increased substantially. However, many questions remain unanswered and the subject is likely to receive further attention following recent access to previously restricted archival material in Eastern Europe. In this paper, based on the English language literature, the author explores the role of medicine, and in particular psychiatry, in defining the bio-medical vision that was central to Nazi ideology. PMID- 8481156 TI - Ethical standards and clinical practice. PMID- 8481157 TI - Juries and psychologically disturbing cases. PMID- 8481158 TI - The Australian multicentre moclobemide trial. PMID- 8481159 TI - A case register for neuroleptic malignant syndrome. PMID- 8481160 TI - Sex and gender and the impaired therapist. PMID- 8481161 TI - Sex and gender and the impaired therapist. PMID- 8481162 TI - Obstructive sleep apnoea and depression. PMID- 8481163 TI - Combined fluoxetine and desipramine in resistant depression. PMID- 8481164 TI - Referrals from psychologists. PMID- 8481165 TI - Stability of psychiatric diagnoses in New Zealand psychiatric hospitals. AB - This study examines the stability over a five year follow-up of first admission psychiatric diagnoses assigned in New Zealand psychiatric hospitals in 1980 and 1981. Diagnostic stability is a measure of the degree to which psychiatric diagnoses remained unchanged at a later hospital admission. Reasonably high levels of stability were found for the initial diagnoses of substance abuse disorders (86% stable), anorexia nervosa (70%), schizophrenia (67%), and affective disorder (67%). Poor levels of stability were noted for the initial diagnoses of personality disorder (36%), other psychosis (excluding schizophrenia and affective psychosis) (22%), and other neurosis (excluding neurotic depression) (20%). The major trends in diagnostic change are described. Factors influencing diagnostic instability are also examined. For patients with an initial diagnosis of schizophrenia, a change in hospital is found to be the strongest factor causing diagnostic instability, with time between admissions and age at first admission also having a significant influence. The implications of these findings are discussed. PMID- 8481166 TI - Post-traumatic stress disorder in Australian prisoners of the Japanese: a clinical study. AB - The clinical findings of examination of 11 Australian prisoners of the Japanese (POWs (J)) are reported. They were examined for evidence, past or present, of Post-Traumatic Stress Disorder (PTSD). Three currently satisfied the DSM-III-R criteria for a diagnosis of PTSD and at least three more would probably have done so if a complete assessment had been possible. All but two described many of the symptoms of PTSD and would probably have satisfied the criteria for the diagnosis at some time following their release from captivity. The subjects were all seen between mid 1988 and mid 1990 and the difficulties of the study and its implications are discussed. PMID- 8481167 TI - Screening for psychiatric symptoms and illness behaviour in a pain clinic. AB - Evolution of a multidisciplinary pain clinic in a rehabilitation hospital is described. The assessment process was facilitated, particularly with respect to psychiatric and psychological evaluation, by the preliminary administration of two well established but simple self-administered questionnaire instruments, the Illness Behaviour Questionnaire (IBQ) and the Crown-Crisp Experiential Index (CCEI). The characteristics of our pain clinic population are described. They demonstrate questionnaire profiles which are typical of pain patients. Attention is drawn to the CCEI profile now shown in three studies of pain patients, predominance of the somatic anxiety (S) scale occurring in all. Correlations between the IBQ and CCEI showed, inter alia, that the S scale is a measure of somatisation in pain patients. This paper aims to describe the changes in the clinic since previously published descriptions, to note the characteristics of our patient on the questionnaire instruments and to comment on the value of these questionnaires in the assessment of psychiatric symptoms and somatisation in pain clinic patients. PMID- 8481168 TI - Mortality of public mental health patients: a Singapore experience. AB - This study reports the Standardised Mortality Ratio (SMR) by age and sex among public mental health patients in Singapore. The authors also examine the differences between those who were classified as "inpatient deaths" and those who were classified as "outpatient deaths". Mortality was 5.1 times that of the general population and the SMR was most accentuated in the younger, female patients. Of the 217 deaths documented over two years, schizophrenia was the most common diagnosis. Inpatient deaths (N = 120) occurred in older patients with prior physical illness who died of natural causes. In contrast, outpatient deaths (N = 97) involved younger patients with no previous illness and the majority jumped to their deaths. Mortality studies are necessary in monitoring the efficacy of mental health provisions. PMID- 8481169 TI - How many bed-days for an area's psychogeriatric patients? AB - Data were obtained concerning all admissions during a four-year period of persons aged 65 years and over, from a defined catchment area, to the general hospital psychiatric units in the area or to the nearest psychiatric hospital. The mean length of stay was 41.3 days. Of 449 admissions, 55% were diagnosed as having affective disorder or adjustment disorder with depressed mood, but this group accounted for 65% of the bed-days in the acute units with a mean length of stay of 49.2 days. Dementia cases accounted for 24% of admissions and 23% of bed-days. At present, the recommended number of acute psychogeriatric beds to serve this population of 34,000 elderly is 22; development of a comprehensive psychogeriatric service with appropriate community staffing may make it possible to reduce this number. PMID- 8481170 TI - A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness. AB - The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline. PMID- 8481171 TI - Prediction of response to antidepressant medication by a sign-based index of melancholia. AB - We examine the capacity of a new melancholia index (focussing on CORE signs indicative of psychomotor change) to predict response to antidepressant medication. In a naturalistic study, depressed patients were assessed and rated by their treating psychiatrist, and we focus on those who received antidepressants for three weeks or more. Those subjects who returned high CORE scores (putative melancholia) at baseline improved more over the initial six weeks, but analyses suggested that the differential improvement outcome was independent of medication. Thus, CORE scores predicted outcome for those receiving antidepressant medication, but possible mechanisms remain unresolved. PMID- 8481172 TI - The relationship between psychosocial factors and developmental outcome for very low and extremely low birthweight infants: a review. AB - Over the last quarter century, the improved survival rate of very low birthweight infants has sharpened questions about their residual disabilities. Longitudinal studies have devoted attention to the cognitive and neurodevelopmental outcome of these infants, but much less is known about their long-term social and emotional development. Psychiatrists consulting to neonatal intensive care units and assessing these infants in their families, will be assisted by a better understanding of the developmental and psychological outcomes of such infants. This paper reviews the state of knowledge in both of these areas. It argues the paramount importance of psychosocial factors to the infants' developmental outcome, and the importance of longitudinal research in further clarifying the predictive value of these factors. In a subsequent paper, we consider the efficacy of interventions with this group. PMID- 8481173 TI - Psychosocial interventions for very low birthweight infants: their scope and efficacy. AB - With the burgeoning of infant psychiatry, and the increasing survival and development of cohorts of very low birthweight (VLBW) infants, psychiatrists are becoming increasingly involved with other professionals in designing and implementing early intervention programs. Psychosocial interventions for VLBW infants generally report positive results regardless of the orientation of the practitioners, or the stated goal of the intervention: however, they have often taken place independently of longitudinal research, and sometimes without grounding in theories of infant and family development. This paper first reviews the current state of research and findings related to infant-focussed, parent directed, and interactional programs. Second, it addresses a number of basic questions to be considered by psychiatrists involved in consulting to neonatal intensive care units, who have to appraise, design or implement intervention programs with this group. Throughout this discussion, it is proposed that the notion of infants at developmental risk needs to be supplemented by that of caregivers at risk, and that the professional boundaries which these distinctions represent need to be overcome. PMID- 8481174 TI - The essentials of psychoanalysis. AB - Psychoanalysis, as procedure, theory and therapy, is a unique activity centred around a special approach to a formalised intersubjective relationship. The phenomena of transference and counter-transference between analyst and analysand allow the emergence of a generative interplay between creative impulses struggling for expression and a persistent search for clarity by appropriate analytic interpretations and synthetic constructions of what takes place. PMID- 8481175 TI - Human immunodeficiency virus infection, dementia and the older patient. AB - Australian statistics have shown that 10.9% of AIDS cases have occurred in the 50 years and over age group. To date little attention has been given to the many issues surrounding HIV infection in the older population, for example, the failure to consider HIV as an aetiological factor in the older person presenting with neuropsychiatric disorder and the potential for misdiagnosis of AIDS dementia complex as dementia of the Alzheimer type. This paper includes a discussion of the clinical features of the AIDS dementia complex, its resemblance to the syndrome of "subcortical dementia", and review of the literature reporting dementia as the presenting feature of HIV infection in older individuals. PMID- 8481176 TI - Surveillance for colorectal cancer. PMID- 8481177 TI - Use of the metyrapone test for assessing pituitary-adrenal function. PMID- 8481178 TI - HIV prevalence among Washington, DC, residents having abortions. PMID- 8481179 TI - Antineoplastons: the controversy continues. PMID- 8481180 TI - Breaking of transplantation tolerance after reduction of immunosuppression. PMID- 8481181 TI - Breaking bad news. PMID- 8481182 TI - Ethics committees: is the tail wagging the dog? PMID- 8481183 TI - Therapeutic biliary endoscopy and laparoscopic cholecystectomy. PMID- 8481184 TI - Clinical and histopathologic changes in the host cornea after epikeratoplasty for keratoconus. PMID- 8481185 TI - Microalbuminuria, lipoproteins, and diabetic control. PMID- 8481186 TI - Hodgkin disease and HIV. PMID- 8481187 TI - Does sucralfate impede levothyroxine therapy? PMID- 8481188 TI - Telephone directory listings of presumptive Chinese surnames: an appropriate sampling frame for a dispersed population with characteristic surnames. PMID- 8481189 TI - Unnecessary morbidity following irradiation of lateralized head and neck carcinoma. PMID- 8481190 TI - The relation between experience and outcome in heart transplantation. PMID- 8481191 TI - Unreconstructed man. PMID- 8481192 TI - A method for removal of broken vertebral screw. PMID- 8481193 TI - Update on the dementia spectrum of depression. PMID- 8481194 TI - Eating disorders and social phobia. PMID- 8481195 TI - Another example favouring the location of BPES at 3q2. PMID- 8481196 TI - Sustained-release niacin for low levels of high-density lipoprotein cholesterol. PMID- 8481197 TI - Liver dysfunction in CJD. PMID- 8481198 TI - Flunarizine and essential tremor. PMID- 8481199 TI - Reappearance of end-diastolic velocities in the umbilical artery following maternal volume expansion: a preliminary study. PMID- 8481200 TI - Measles vaccine: titre and safety. PMID- 8481201 TI - Brain research in Europe. PMID- 8481202 TI - Hazards of antagonizing narcotic sedation with naloxone. PMID- 8481203 TI - Twin studies: genetic factors are important. PMID- 8481204 TI - Suicide prevention: fact or fiction. PMID- 8481205 TI - Pneumocystosis in patients with acquired immunodeficiency syndrome. PMID- 8481206 TI - Nursing care of patients receiving long-term infusion of neuromuscular blocking agents. PMID- 8481207 TI - Re: Mast cell infiltration in intestine used for bladder augmentation in interstitial cystitis. PMID- 8481208 TI - Patterns of elder abuse. PMID- 8481209 TI - Re-emergence of tuberculosis. PMID- 8481210 TI - Tuberculosis: the return of an old enemy. AB - Tuberculosis is an ancient human scourge that continues to be an important public health problem worldwide. The increasing number of multidrug-resistant (MDR) M. tuberculosis isolates from both AIDS and non-AIDS patients is an ominous trend that threatens tuberculosis eradication programs both in the U.S. and overseas. New antituberculosis vaccines with therapeutic properties are urgently needed for human immunodeficiency virus-infected individuals, as well as health care professionals likely to be exposed to MDR tubercle bacilli. Recombinant DNA vaccines bearing protective genes from virulent M. tuberculosis are being developed using shuttle phasmids to transfer genetic material from one mycobacterial species to another. Improved assay procedures are needed to measure the protection afforded by these new vaccines under experimental and field test conditions. Tuberculosis vaccine development should be given a high priority in current medical research goals. PMID- 8481211 TI - Biomass growth rate during the prokaryote cell cycle. AB - The rate of biomass growth throughout the cell cycle of prokaryotes is important in the study of global regulation. Two limiting cases have generally been considered: the exponential model and the linear model. The exponential model is a logical expectation because protein, the main component of biomass of a bacterial cell, increases continuously during the cell cycle and therefore the means for synthesis of other cell components and metabolites also increases. In addition, during the cell cycle, ribosomes, the means of production of proteins, increase monotonically. As a consequence, the increase of all should be autocatalytic and the content of cell substance should be an exponential function of time. Two cellular components would not be expected to increase exponentially: the DNA and the cell envelope. The former because of the intermittent synthesis of the chromosome, and the latter because of changes in the surface-to-volume ratio with growth and division. In contrast to the exponential model, the linear model of Kubitschek postulates that the cell only increases its membrane transport capability over a brief period during the cell cycle, and, thus limited by transport, all cell components can increase only at a constant linear rate during most of the cell cycle. Other proposed models are intermediate and assume that the growth rate of the cell depends on some cell cycle event, such as the initiation of chromosome replication. The models have relevance to prokaryotes undergoing balanced growth; they may not be relevant to eukaryotic microbes or to eukaryotic cells in tissue culture that have endogenous rhythms or are controlled by protein growth factors. Logically, the models could possibly apply to a free living cell that does not respond to environmental cues. Even under rigidly constant conditions, however, cells may try to respond to a stimulus that was periodic or regulatory under natural conditions, but is present at a constant level under the experimental culture condition. There are four classes of experiments that have been used to measure the accumulation of dry biomass or its components during the cell cycle of a bacterium, as typified by Escherichia coli. For the first class of experiments, the dimensions of living cells are measured under the microscope. So far, the experiments have been limited by the resolving power of the phase microscope, but adequate resolution should be possible with the confocal scanning light microscope or various video computer systems. Such experiments are called integral because augmentation of cell constituents is followed. The second class involves pulse-chase labeling of cells and then their separation into different phases of the cycle or age groups and measurement of the radioactivity per cell in the fractions. Such experiments are called differential in that the rate is measured directly instead of being deduced by comparing the total size at different times.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481212 TI - The prochlorophytes: are they more than just chlorophyll a/b-containing cyanobacteria? AB - The prochlorophytes are a diverse group of photosynthetic prokaryotes that fall within the cyanobacterial lineage, yet lack phycobilisomes as light harvesting structures. Instead, the prochlorophytes have a light-harvesting apparatus composed of the higher plant pigments chlorophylls a and b. This review discusses the evolutionary relationships among these bacteria, with focus on the structure and function of the photosynthetic apparatus. This analysis yields a consensus from studies both on Prochloron sp. and Prochlorothrix hollandica as to how the thylakoid membrane is organized. Overall, we propose that the structure of the light-harvesting complexes (LHC) from prochlorophytes is very different from those of chloroplast systems, and is evolutionarily very ancient. The functional association of the light-harvesting apparatus with photosystem I (PSI) in both Prochlorothrix and Prochloron, as well as a demonstrated capacity for PSI dependent anoxygenic photosynthesis in Prochlorothrix, may indicate that there is an increased dependence on cyclic photophosphorylation in these organisms. Finally, the structure of the prochlorophyte thylakoid membrane is discussed with respect to the forces that drive thylakoid membrane stacking in prochlorophytes and chloroplasts. We suggest that the light-harvesting structures in prochlorophytes play little, if any, role in this process. PMID- 8481213 TI - Disease flare with gonadotrophin-releasing hormone (GnRH) analogues. How serious is it? PMID- 8481214 TI - Contraceptive choice for women with 'risk factors'. AB - Women with many medical conditions need to plan their families with special care. For such women, the risk of complications with particular contraceptive methods is increased. Women with severe hypertension, a previous myocardial infarction or venous thromboembolism, or cerebrovascular stroke have a significant risk of problems in pregnancy, and should avoid the combined pill. The combined pill may increase the risk of cardiovascular disease in patients with diabetes mellitus and may worsen the severity of migrainous headaches in susceptible patients. Women with active hepatitis should wait for liver function tests to normalise before becoming pregnant or starting the combined pill or injectable progestogen. Control of epilepsy may deteriorate with use of the combined pill; this is probably because of the risk of drug interactions. Similarly, contraceptive control may also fail in women receiving rifampicin (rifampin) concurrently with contraceptive steroids. Intrauterine contraceptive devices should not be used in women who have experienced previous episodes of pelvic inflammatory disease, or with previous malignancy of the genital tract until complete cure is likely. Other conditions which may appear, become more common or worsen when the combined pill is prescribed include hepatic adenoma, gall bladder disease, ulcerative colitis, alopecia, hirsutism and acne. Some of these conditions are potentially hazardous to the woman's health, in which case combined pill use should be stopped. If the condition is unchanged then the combined pill may sometimes be reintroduced with caution. PMID- 8481215 TI - Adverse reactions and drug interactions with radiopharmaceuticals. AB - Adverse reactions to radiopharmaceuticals are comparatively few in number. Various estimates quote an incident rate of 1 to 6 reactions per 100,000 injections. Other figures quoted are 1 in 800 for the bone-seeking radiopharmaceutical methylene diphosphonate, and 1 in 400 for the lung visualisation agent macroaggregated albumin. The very low numbers of reported adverse effects probably reflect the tiny amounts of material which are used in the formulation of radiopharmaceuticals. Adverse reactions to radiopharmaceuticals are usually mild and transient and require little or no medical treatment. A few reactions involve respiratory or circulatory collapse or loss of consciousness. Several fatalities have been reported with the liver scanning agent 99mTc (technetium 99m)-albumin colloid. Clinical manifestations may be categorised under the headings of vasomotor effects i.e. faintness, pallor, diaphoresis or hypotension, and anaphylactoid effects such as nausea, dermographism, wheezing, bronchospasm, erythema and pruritus. The most prominent group of radiopharmaceuticals that have been reported to produce adverse events are the diphosphonates, which are used for scanning the skeleton. Typical diphosphonate reactions include erythema (especially over the extremities), nausea, vomiting and malaise. The onset of reaction is usually 2 to 3 hours after injection. The second group of radiopharmaceuticals which give rise to adverse events are the colloids, which are used for liver and spleen scintigraphy. Typical colloid reactions include pallor, nausea, flush and pulse changes. Adverse events may also occur as a result of the patient's medication interfering with the disposition of the radiopharmaceutical. Although not usually hazardous or dangerous, such events may be so pronounced that a marked deviation in the expected pharmacokinetics may occur. Drug interactions can be conveniently categorised under the headings of unusual handling of the radiopharmaceutical because of pharmacological action, genuine in vivo interaction between the medication and radiopharmaceutical, drug-induced disease and interaction between the radiopharmaceutical and catheters or syringes. The most serious drug interactions are those where the patient is taking cortisone or cytotoxic agents prior to tumour scintigraphy. Other important effects occur in patients undergoing bone scanning who are receiving iron preparations. Nifedipine has been reported to produce quite severe problems in scanning, including difficulties in the radiolabelling of red cells (for cardiac scintigraphy), and other effects where the drug appears to prevent the transport of bone-seeking materials into the skeleton. Many drugs alter hormonal status and these effects may produce marked deviations from the expected biodistribution. Diethylstilbestrol (stilboestrol), digitalis, gonadotrophins, phenothiazines and cimetidine all increase estrogen levels in high doses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481216 TI - Adverse effects of antimalarials. An update. AB - Various drugs are widely used in the prophylaxis and treatment of malaria. In the prevention of malaria in travellers, a careful risk-benefit analysis is required to balance the risk of acquiring potentially serious malaria against the risk of harm from the prophylactic agent. Unfortunately, the information needed to perform accurate analyses of this type is not available for most antimalarials. In the prophylaxis of malaria, chloroquine and proguanil have an excellent safety record, being very rarely associated with severe adverse reactions in the recommended dosages. However, in many parts of the world they are no longer effective prophylactic agents. Pyrimethamine-dapsone (Maloprim) is associated with agranulocytosis, especially if the recommended dose is exceeded, and should be reserved as a second-line agent for travellers to high risk areas. Pyrimethamine-sulfadoxine (Fansidar) and amodiaquine are associated with a relatively high incidence of potentially fatal reactions, and are no longer recommended for prophylaxis. Mefloquine, a relative newcomer, may provoke severe neuropsychiatric reactions with a frequency of 1 in 15,000 to 20,000 users at the prophylactic dosage. In the treatment of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial drugs is acceptable. As chloroquine resistance has become widespread, alternative agents including quinine, mefloquine, pyrimethamine sulfadoxine, tetracyclines, halofantrine and artemisinin (qinghaosu) and its derivatives may be used in treatment regimens. The therapeutic ratios for chloroquine, quinine and mefloquine are narrow and toxicity is frequent when recommended treatment dosages are exceeded; parenteral administration above the recommended dose range is especially associated with the hazards of cardiac and neurological toxicity. PMID- 8481217 TI - Zidovudine toxicity. Clinical features and management. AB - Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable. PMID- 8481219 TI - [Psychotic intoxication and a psychotic episode]. AB - A man 27 years with a breath alcohol concentration of 0.7 g/kg had delusional ideas and other signs that indicate a psychotic intoxication. By the end it was a psychotic episode however concerning a patient with a polytoxicomania--the drugs were alcohol, cocaine, and Phencyclidine. There are no indications for the primary manifestation of a psychosis. PMID- 8481218 TI - Effects of terfenadine on psychomotor performance. An overview. AB - Sedation and impairment of psychomotor performance are well known adverse effects of the traditional antihistamines. These effects appear to be caused by different mechanisms, but both may have potentially dangerous consequences. while several of the newer antihistamines, such as terfenadine, have overcome the problem of sedation, it is also important to establish their propensity to cause psychomotor impairment. Many single- and multiple-dose studies (mostly in healthy volunteers) have compared the effects of terfenadine on psychomotor performance with those of placebo, as well as traditional and other nonsedating antihistamines. Over half of the studies employed divided-attention tasks that are considered relevant to everyday activities, such as driving. Like several other nonsedating antihistamines, single doses of terfenadine of up to 120 mg did not impair driving performance and generally had no significant effects on other psychomotor tests compared with placebo. In most of the multiple-dose studies, terfenadine 60 mg twice daily was administered for up to 5 days. Again, the effects of terfenadine on psychomotor performance differed little from those of placebo. Thus, the available evidence suggests that the problem of impaired psychomotor performance associated with the older, traditional antihistamines does not apply to terfenadine. PMID- 8481220 TI - [Exceptions for revoking the driver's license of alcohol intoxicated drivers at apprehension and during initial withdrawal]. AB - Exceptions from the withdrawal of permission to drive should be allowed primarily to first offenders. In case of alcohol conspicuous first offenders a post schooling course has a positive influence to exceptions, if a favourable prognosis for the future can be made especially in case of total abstinence instead of "Controlled Drinking": In spite of longstanding good reputation (minimum 25 years) exceptions to the withdrawal of permission to drive are excluded if the blood alcohol concentration exceeded 1.8/1000. PMID- 8481221 TI - [Revoking the driver's license, assessment of driver competence, re-education and therapy in alcohol offenses: approaches to a necessary reorientation]. AB - After representing figures and facts about drinking behaviour and drinking driving offences of the 45 mio. drivers in Germany counter-measures for DWI offenders are dealt with. The proceedings practised so far are critically analysed and new approaches are discussed. Primarily reviewed are special preventive measures and here particularly the selection procedure usually applied in Germany, in which on demand of the driver licensing authorities the question is to be answered by expert opinions whether there is to be reckoned with driving under the influence in die future, too. It is pointed out that the expert opinions are not valid enough for making a distinct decision in an individual case. Validity coefficients obtained in evaluation studies lie between phi = 0 and .28, raising the expectancy value of 50% resulting by chance at best only on to 65%. Moreover the psychological interview is understandably burdened with faked answers of the explored person, in several cases increased by a specific, professionally managed preparation for the testing situation. As a way out of the dilemma expert opinions prognosticating driver behaviour should be waived in favour of making diagnoses and proposals for treatment. The timing of regranting the driver license is then only determined by the revocation period pronounced by the court and by the performance of the measures recommended by the experts and demanded by the licensing authority. As a support for such a procedure a more consistent and resolute administration of the judicial revocation of driver license with longer periods for repeaters should be provided. Besides there is necessary a wider range of rehabilitation programs for drivers with alcoholic problems. PMID- 8481222 TI - [Effect of Kava-Special Extract WS 1490 combined with ethyl alcohol on safety relevant performance parameters]. AB - The Kava-special extract WS 1490 (3 x 100 mg/d over 8 days) was tested in a placebo-controlled randomised double-blind study to establish whether it has any adverse effects on safety-related performance when administered together with ethyl alcohol (0.05% blood alcohol concentration). The study was carried out as a comparison of two independent groups each containing 10 male and 10 female healthy volunteers aged between 18 to 60 years (mean: 40.45 +/- 12.2 years). The batteries of performance tests consisted of seven procedures. It was conducted before treatment without alcohol as well as the 1st, 4th and 8th day of treatment together with alcohol. The results showed no negative multiplicative effects caused by the Kava-special extract WS 1490 together with alcohol. With the concentration test however there was a remarkable advantage of the WS 1490 group at the 4th day of treatment (p < 1%). The collection of well-being data as well as the description of adverse events proved WS 1490 to be well tolerated. PMID- 8481223 TI - Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). II. Neurological, psychiatric, and demographic influences on baseline measures of disease severity. AB - The "Predictors Study" is a prospective cohort study of the natural history of Alzheimer disease (AD), the aim of which is to identify milestones in disease progression and to develop a model to predict disease course in individual patients. The empirical background to this study is based on previous reports that the presence of extrapyramidal signs (EPS), myoclonus, and psychosis in AD may signify greater disease severity at any given stage and a more rapid course of the disease over time. The present analyses were conducted to determine whether these independent "predictor" variables were associated with greater disease severity at baseline within a new cohort of 224 mild AD patients recruited from three different medical centers (in New York, Baltimore, and Boston). Measures of disease severity were provided by the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale (BDRS), which measures functional capacity. Independent variables were EPS, delusions, and slowing of the posterior dominant EEG rhythm. The frequency of myoclonus and hallucinations was too low to permit adequate statistical assessment of their effects at this time. EPS and EEG slowing were associated with low mMMSE scores, whereas delusions were primarily associated with impaired functional capacity. These effects were independent of the influence of age and disease duration. These results indicate that the effects of these independent variables can be detected at mild stages of AD and that these effects can be generalized across different geographical regions. PMID- 8481224 TI - Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). I. Study design, cohort description, and intersite comparisons. AB - Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The "Predictors Study," a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed. PMID- 8481225 TI - A retrospective study of syphilis seropositivity in a cohort of demented patients. AB - A retrospective study of 376 patients with dementia was performed to determine the rate of syphilis seropositivity. Subjects were seen over a 2.5-year period and received medical, social, psychiatric, neurological, and laboratory evaluations. Mean age was 74 years and 73% were women. Diagnoses included Alzheimer's disease (AD; 29.8%), vascular dementia (VascD; 24.7%), combined AD/VascD (14.3%), and other diagnoses (31.2%). Dementia was moderately advanced with a mean Folstein Mini-Mental State Score of 16. Fluorescent treponemal antibody absorption tests (FA) were performed on 338 of the patients with 10.9% being reactive. Two of nine subjects with reactive FA's had reactive rapid plasma reagin tests. PMID- 8481226 TI - Wide third ventricle correlates with low choline acetyltransferase activity of the neocortex in Alzheimer patients. AB - We evaluated central, temporal, and cortical atrophy by linear measurements on brain computed tomography (CT) in 17 patients with moderate to severe histologically verified Alzheimer disease (AD) compared with findings in 84 nondemented elderly controls. Measurements were adjusted for age and head size. The AD patients had wider third and lateral ventricles as well as larger temporal horns and Sylvian fissures compared with controls. Cortical atrophy tended also to be more pronounced for AD patients relative to controls. Thus measures of central and temporal atrophy clearly distinguished AD patients from normal aged individuals. In AD patients, the width of the third ventricle was significantly correlated with the choline acetyltransferase (ChAT) activity in the post-mortem frontal cortex (r = 0.65, p = 0.005) and in the temporal cortex (r = 0.59, p = 0.006). CT measures did not correlate significantly with neurofibrillary tangle or senile plaque scores. The result suggests that the width of the third ventricle better reflects the degree of cholinergic deficit than severity of histopathological changes, scores of plaques, and tangles in AD. PMID- 8481227 TI - Neuropathologic diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles. AB - A diagnosis of definite Alzheimer disease (AD) is made when there is a history of progressive dementia combined with the pathologic findings of numerous senile plaques and neurofibrillary tangles in neocortex. Recent studies have shown, however, that there may be significant interrater variability in the quantitation of these histopathologic lesions. In the present two-center study, interrater reliability and test-retest reliability for plaque and tangle counts were examined when histologic staining and sampling were controlled. We report similar levels of reliability for plaque and tangle counts in 35 cases of AD, nine normal elderly controls and six non-AD dementias: Pearson correlations for interrater reliability ranged from 0.68 to 0.88, and from 0.97 to 0.99 for test-retest reliability. Using quantitative cut-points, concordance between laboratories for experimental diagnoses of AD versus non-AD made on the basis of these lesion counts ranged from 84 to 92% (kappa scores: 0.69-0.84). The agreement between these experimental diagnoses and the clinicopathologic diagnoses of record ranged from 74 to 86% (kappa scores: 0.50-0.71). Thus, under optimal conditions, a moderate to substantial degree of interrater reliability can be attained in the pathologic diagnosis of AD. PMID- 8481228 TI - Alzheimer disease (AD), modified proteins, and aspirin. PMID- 8481229 TI - Cellular and molecular aspects of antigen processing and the function of class II MHC molecules. AB - Antigen processing is the conversion of native antigen molecules into short peptides that can then bind to major histocompatibility complex (MHC) molecules. Class II MHC (MHC-II) molecules target to endocytic compartments, where they bind peptides that are produced by internalization of extracellular antigens and subsequent antigen catabolism. The resulting peptide-MHC complexes are displayed on the surface of antigen-presenting cells for recognition by T cells. Thus, MHC II molecules first serve as peptide receptors that rescue peptides from total lysosomal degradation and transport them to the plasma membrane; the MHC-II molecules then form a composite peptide-MHC-II determinant that is recognized by the T cell receptor. Recent work has begun to clarify the molecular events and transport mechanisms that govern antigen processing. PMID- 8481230 TI - Early-passage rat lung fibroblasts do not migrate in vitro to transforming growth factor-beta. AB - Lung fibrosis has been postulated to be mediated by the production of macrophage derived growth factors that are both mitogenic and chemotactic for fibroblasts. In vitro studies from our laboratory demonstrated that alveolar and interstitial macrophages treated with iron and asbestos release platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) into the media. This conditioned media was capable of inducing proliferation and chemotaxis of primary rat lung fibroblasts (RLF). TGF-beta is known to be present in the media, and RLF have high-affinity receptors for TGF-beta. However, we found that > 95% of the chemotaxis was blocked by a polyclonal anti-PDGF antibody, whereas anti-TGF-beta did not change cell migration. TGF-beta has been described previously as a potent chemoattractant for fibroblasts. Thus, we tested the potential of purified TGF beta to induce RLF chemotaxis in an attempt to address this apparent contradiction in results. Four separate preparations of RLFs from four different rats, Swiss 3T3 cells, human and rat fetal skin fibroblasts, and human foreskin fibroblasts were tested for chemotaxis using purified porcine TGF-beta 1 as well as human TGF-beta. None of these cells responded chemotactically to TGF-beta over a broad range of concentrations used (0.004 pg/ml to 50 ng/ml). RLF plated at different densities also did not respond to TGF-beta. On the other hand, all the fibroblast types migrated vigorously to PDGF (4 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481231 TI - Explant culture of rabbit tracheobronchial epithelium: structure and prostaglandin metabolism. AB - This study examines the potential usefulness of explant culture of rabbit tracheal epithelium as a model for the study of epithelial function under normal and potentially pathologic conditions. Accordingly, we assessed the structure and prostaglandin E2 (PGE2) release of tracheal epithelial explants obtained from adult pathogen-free rabbits. Epithelial cells attached to their native connective tissue substratum were maintained in culture for 5 days in serum-free medium, under bipolar conditions (air-liquid interface) on a permeable membrane (pore size, 0.2 mm), and nourished from the basolateral surface. At 5 days in culture, scanning and transmission electron microscopy and light microscopy demonstrated a pseudostratified, ciliated columnar epithelium with prominent folds and mucus secretion identical in appearance to the mucosa before culture. On the day of dissection (day 0) and after 4 days in culture (day 4), explants released PGE2 into the medium spontaneously. However, day 4 explants produced 3- to 4-fold greater amounts of PGE2 than day 0 explants. Moreover, day 4 explants demonstrated increased PGE2 release in response to bradykinin, a receptor dependent agonist, and ionomycin, a calcium ionophore, while day 0 explants did not. Primary tracheal epithelial cell cultures grown to confluence (day 9) on a collagen substrate demonstrated PGE2 responses to bradykinin and ionomycin that qualitatively resembled those of day 4 explants. We conclude that rabbit tracheal explants cultured in vitro under the above conditions maintain cellular differentiation, in situ three-dimensional organization, and PGE2 synthetic pathways over several days in culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481232 TI - Relationship of secretory granule content and proliferative intensity in the secretory compartment of the hamster bronchial epithelium. AB - We have previously shown that normal hamster airway epithelial secretory cells have a lower proliferative intensity than basal cells, but because of their high frequency are a major contributor to cell renewal (Am. J. Respir. Cell Mol. Biol. 1990; 2:51-58). In the present experiment, the relation between proliferative intensity and secretory granule content in bronchial epithelial cells is studied. [3H]thymidine (2 microCi/g wt) was given intraperitoneally, 1 h before killing, to 5 hamsters treated 21 days earlier with intratracheal saline and to six hamsters in which secretory cell metaplasia had been induced by intratracheal treatment with 300 micrograms of human neutrophil elastase given 21 days earlier. Light microscopic autoradiograms were prepared from 2-microns-thick Epon sections of left intrapulmonary hilar bronchi. Cells were categorized as basal, ciliated, secretory, or indeterminate. Secretory cells were classified as either: S1, with 0 to 4 granules; S2, with > or = 5 granules with intervening cytoplasm; or S3, with abundant granules and no apparent supranuclear cytoplasm. Proliferative intensity was defined by the categorical labeling index (LIc) at 1 h after [3H]thymidine injection. LIc was determined by the number of labeled cells in a category as the percent of labeled and unlabeled cells of that category. LIc of each of the cell categories were similar in the elastase and saline groups. LIc was highest for basal cells, reflecting their proliferative intensity, and lowest for ciliated cells. In the saline group, LIc of S1 (0.25%) was significantly higher compared with S2 (0.13%); S3 cells were rare (0.2%) and none were labeled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481233 TI - Pulmonary macrophages suppress the proliferation and cytotoxicity of tumor infiltrating lymphocytes. AB - Adoptive immunotherapy with interleukin-2 and tumor-infiltrating lymphocytes (TIL) is rarely effective in primary lung cancer. We hypothesize that pulmonary macrophages (PM), which are increased substantially in the lungs of smokers, might suppress TIL function. The addition of PM into the TIL cytotoxicity assay produced a concentration-dependent suppression of TIL cytotoxicity with up to 71% inhibition of autologous tumor killing at the 1:1 PM:TIL ratio. Inhibition was not target-specific, as killing of NK-sensitive (K562), NK-resistant (M14), and autologous tumor targets were equally suppressed. Nor was inhibition specific for lung TIL, as similar inhibition was observed with melanoma and renal TIL. Using a model system, we demonstrated that both CD3+ antigen-specific and CD56+ nonspecific lymphocytes are susceptible to the suppressive effects of the PM. Direct co-incubation of PM and TIL for 4 to 44 h resulted in progressive suppression of TIL proliferation and cytotoxicity. TIL cytotoxicity remained suppressed even if PM were removed from the co-culture after 24 h, but was restored if the separated TIL were re-incubated in interleukin-2. These results suggest that PM may locally regulate the proliferative and cytotoxic function of adoptively transferred TIL. PMID- 8481234 TI - Distribution of manganese superoxide dismutase mRNA in normal and hyperoxic rat lung. AB - Aerobic metabolism requires a continuous oxygen supply, which in turn can form partially reduced species (free radicals) that damage cellular components. To prevent this, organisms have elaborate free radical-scavenging defenses that include the superoxide dismutases. The lungs are unique in their role as an oxygen-gathering system, making these defenses critical to lung integrity. Manganese superoxide dismutase (Mn-SOD) levels increase in rats exposed to sublethal doses of hyperoxia and correlate with the development of tolerance to higher levels of hyperoxia. Although pulmonary Mn-SOD protein and mRNA levels both change with hyperoxia, the timing and levels differ dramatically. Lung heterogeneity makes extrapolation of data from whole tissue homogenates or cultures difficult. In this study, in situ hybridization of Mn-SOD in the lungs of adult rats exposed to air or to 85% O2 for 3 days was performed. In animals exposed to either air or 85% O2, Mn-SOD transcripts were present in arterioles, the septal tips of alveolar ducts, alveolar type II cells, and mesothelial cells. Hyperoxic lung had an intense, continuous labeling of the pleura that was distinctly greater than the intermittent labeling of the pleura found in control animals. The high level of expression of Mn-SOD mRNA in alveolar duct septal tips in both control and O2-exposed animals may be secondary to increased aerobic activity in these regions, which contain collagen and elastin and are important stress-bearing elements in the lung. Alveolar type II cells are metabolically active secretory cells and thus may experience increased endogenously generated oxidative stress. Pleural effusions are common after hyperoxic exposures, suggesting damage to the mesothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481235 TI - Fibulin's organization into the extracellular matrix of fetal lung fibroblasts is dependent on fibronectin matrix assembly. AB - Fibulin is a newly described extracellular matrix (ECM) glycoprotein whose function has not been elucidated. We have observed that cultured fetal lung fibroblasts produce fibulin and have postulated that its expression may be important during lung development. To begin to understand the potential function of fibulin in lung development, we examined its expression and distribution in cultured fetal lung fibroblasts. Immunofluorescence staining of cultured fibroblasts revealed that fibulin was distributed upon their surface in a fibrillar array resembling fibronectin (FN), another ECM glycoprotein expressed by fetal lung fibroblasts and implicated in lung and heart development. Detection of fibulin by immunofluorescence staining of nonpermeabilized cells, its immunoprecipitation from 125I-cell surface-labeled fibroblasts, pulse-chase analysis, and temperature-induced phase separation studies revealed that fibulin is an ECM peripheral membrane protein that is synthesized and secreted by cultured fetal lung fibroblasts shortly after plating and incorporated into their matrix in a divalent cation-dependent manner. Because fibulin co-distributes with both FN and the FN receptor, the integrin alpha 5 beta 1, we examined the possibility that fibulin was interacting with both components. Dissociation of FN receptors from FN fibers with anti-FN receptor antibodies did not affect fibulin's distribution, suggesting that fibulin binds FN and that this interaction is not affected by the state of FN receptor binding. Finally, inhibition of FN matrix assembly prevented the deposition of fibulin, providing further support for FN-fibulin interactions and suggesting that fibulin deposition is dependent on FN matrix assembly. PMID- 8481236 TI - Secretion of surfactant protein A and phosphatidylcholine from type II cells of human fetal lung. AB - Surfactant protein A (SP-A) appears to have a role in lung immune defense as well as generation and metabolism of the alveolar surface-active film. Previous studies indicated that lamellar bodies isolated from lung tissue had a relatively low content of SP-A and that exogenous SP-A was needed for rapid formation of a surface-active film in vitro. We therefore tested the hypothesis that SP-A was secreted from type II cells primarily by a pathway separate from lamellar bodies. Cells were isolated from explants of human fetal lung that had been cultured with hormones to promote differentiation of type II cells, and secretion of surfactant lipid and SP-A were compared. Cultured cells secreted labeled phosphatidylcholine in a nearly linear fashion for 48 h. Basal secretion of SP-A, assayed by enzyme linked immunosorbent assay, was linear for only 12 h after plating of cells; during this time, there was no accumulation of intracellular SP-A. Addition of secretagogues (phorbol ester, calcium ionophore, and beta-adrenergic agonist) stimulated phosphatidylcholine secretion approximately 4-fold. In contrast, the secretion rate of SP-A was not significantly affected by secretagogues. These findings indicate that a relatively small amount of secreted SP-A (approximately 10%) is released with lamellar bodies. Most SP-A is released by constitutive secretion and may be important for both surfactant- and nonsurfactant-related functions. PMID- 8481237 TI - Distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cells in vitro and in vivo. AB - The interactions of bronchial epithelial cells with the basement membrane control cell morphology, differentiation, and proliferation in addition to having a major role in malignant transformation. Since these interactions are mediated by the integrin family of cell adhesion receptors, we characterized the integrin repertoire and adhesive properties of normal human bronchial epithelial cells in culture and cell lines derived from nine lung carcinomas using subunit-specific monoclonal antibodies. In addition, the integrin repertoire of three of the transformed cell lines was reexamined after the cells formed tumor nodules in immunodeficient mice. Bronchial epithelial cells in culture expressed multiple integrin subunits with the capability of binding to collagen and laminin (alpha 2, alpha 3, and alpha 6) and at least two subunits that are capable of mediating adhesion to fibronectin (alpha 3 and an alpha v-containing integrin). The alpha v beta 3 vitronectin receptor was not present. This distribution closely mimicked that seen by bronchial epithelial cells in situ. Cell lines derived from transformed pulmonary epithelial cells showed great heterogeneity with respect to integrin expression--some showing fewer, some greater, and some the same types of integrins as nontransformed epithelial cells. Only slight changes in integrin expression were seen in tumor cells propagated in immunodeficient mice. Although the adhesion characteristics of the transformed cells mirrored their adhesion receptor profile, no correlation between integrin profile and the ability to grow in SCID mice was observed. This study defines the integrin repertoire of human bronchial epithelial cells and sets the stage for future investigations exploring how the regulation and signal transduction mechanisms of these receptors might affect important pulmonary processes such as bronchial cell differentiation, wound healing, and malignant transformation. PMID- 8481238 TI - Spontaneous contractility of human fetal airway smooth muscle. AB - Physical forces such as fetal breathing and fluid secretion may influence lung development, perhaps by their ability to distend the fetal lung. We found that airway smooth muscle cells in first-trimester human lung tissue and cultured lung tissue explants spontaneously contract. The contractions caused visible movement of intraluminal fluid and distended the distal ends of the epithelial tubules, suggesting that they produced significant changes in intraluminal pressure. Smooth muscle contractility and responses to pharmacologic manipulations were recorded with video microscopy. The interval between contractions ranged from 8 to 135 s (mean +/- SEM, 54 +/- 5 s; n = 20). Smooth muscle contractility was not inhibited by tetrodotoxin or atropine, implying a myogenic rather than neurogenic origin. Because cholinergic nerves modulate adult airway smooth muscle contractility, we asked whether fetal airway smooth muscle cells were regulated by cholinergic agents. The cholinergic agonists acetylcholine and carbachol both increased fetal airway smooth muscle contractility. Contractions were inhibited by the calcium channel blockers CdCl2 and nifedipine, suggesting that an influx of extracellular Ca2+ accompanied airway smooth muscle contractions. Isoproterenol dilated the contractile regions of the epithelial tubules and stopped contractions. Lemakalim, an activator of smooth muscle ATP-sensitive K+ channels, also arrested contractions and relaxed fetal airway smooth muscle. In conclusion, human fetal airway smooth muscle contacts spontaneously and exhibits pharmacologic responsiveness similar to adult airway smooth muscle. We speculate that fetal airway smooth muscle contractions, possibly exerting effects through phasic changes in intraluminal pressure, may be an important physical force contributing to lung development. PMID- 8481239 TI - Significant mitral regurgitation is protective against left atrial spontaneous echo contrast and thrombus as assessed by transesophageal echocardiography. AB - This retrospective study examines whether a relationship exists between the severity of mitral regurgitation (MR) and the presence of left atrial spontaneous echo contrast and/or thrombus (SEC/THR) as assessed by transesophageal echocardiography in 427 consecutive patients. Clinical data were evaluated in 316 of these patients. Nine percent of patients with MR < or = 2+ versus < 1% of those with MR > or = 3+ had SEC/THR (p < 0.03). Atrial fibrillation, left ventricular dysfunction, mitral stenosis, and mitral valve prosthesis were demonstrated to be independent positive predictors of left atrial SEC/THR, whereas MR > or = 3+ was an independent negative predictor of SEC/THR. SEC/THR was less common in patients with MR > or = 3+ than in patients with MR < or = 2+ for any given number of independent positive predictors of SEC/THR. This relationship did not hold true in patients with a mechanical mitral prosthetic valve. Clinical data revealed a trend towards a lower prevalence of stroke or transient ischemic attacks in patients with MR > or = 3+. Stroke and transient ischemic attacks were significantly more common in patients with SEC/THR (p < 0.001). We suggest that significant MR may be protective against the formation of left atrial SEC/THR. PMID- 8481240 TI - Importance of sampling both pulmonary veins in grading mitral regurgitation by transesophageal echocardiography. AB - Pulmonary venous flow patterns have been used to assess severity of mitral regurgitation; however, the issue of which pulmonary veins to sample has not been determined. We performed pulsed wave Doppler transesophageal echocardiography of both the left and right upper pulmonary veins in 80 patients who had mitral regurgitation determined by independent transesophageal echocardiography color flow mapping. Pulmonary venous flow patterns, peak systolic and diastolic flow, and the presence of reversed systolic flow were compared between the left and right pulmonary veins for each grade of mitral regurgitation. Flow patterns were discordant in 20 (25%) of the 80 patients. Of the 43 patients with 4+ mitral regurgitation, there was discordant flow in 16 (37%) of the patients with mainly reversed systolic flow in the right upper vein, while there was blunted or normal systolic flow in the left upper vein. Of the 16 patients with discordant flows, 14 had eccentric jets, mainly anteromedial jets. We conclude that if discordant flow can occur in 25% of patients with mitral regurgitation and in 37% of patients with 4+ mitral regurgitation, then both pulmonary veins must be evaluated when assessing the severity of mitral regurgitation with pulsed wave Doppler transesophageal echocardiography. PMID- 8481241 TI - Demonstration of dual parallel jet interaction in an in vitro model of multivalvular disease by use of optical visualization and color Doppler flow mapping. AB - Parallel jets, such as those occurring in the heart in multivalvular diseases like combined mitral stenosis and aortic insufficiency, have created difficulty when color Doppler flow mapping or continuous wave Doppler has been used to localize or to measure the jets because they appear to merge. Dual jet interaction was reproduced in an in vitro transparent model by driving two parallel adjacent jets, one lower velocity, higher mass, through a 19 mm2 orifice, and the other higher peak velocity, smaller mass through two orifices, 0.27 mm2 and 1.5 mm2, by use of a solution of India ink and cornstarch to optically visualize the jet interaction and image the interaction by color Doppler. Consistent deviation of the lower velocity jet towards the higher velocity jet was observed, and the large jet angled more strongly towards the small jet for the 1.5 mm2 small jet orifice than for the 0.27 mm2 orifice for constant large and small jet velocities. There was a better linear correlation of the amount of large jet angulation to the ratio of both jets' Reynolds numbers than to the ratio of both flow rates. The jets interacted as close as 1.3 cm from their point of origin, and the region after the jets merged was a highly turbulent mixing zone where neither jet could be separately imaged or visualized. These observations suggest that relative velocity plays a primary role in determining jet interaction which is a recruitment phenomena but that other hydrodynamic parameters, such as flow rate and Reynolds numbers, determine the degree to which the jets deviate. PMID- 8481242 TI - Doppler ultrasound of the subclavian artery as an aid to quantification of aortic insufficiency. AB - Aortic insufficiency (AI) induces backflow of blood in the arterial system that is most pronounced in the major arteries close to the heart. Assuming that the intensity of the arterial backflow of blood may reflect the severity of AI, the systolic and diastolic flow profiles of the subclavian artery were studied in 40 patients with and 10 patients without AI that was angiographically proved by use of continuous wave Doppler ultrasound (8 MHz transducer, supraclavicular approach). Patients with angiographically determined severe AI (n = 17) had significantly higher diastolic regurgitant flow velocities (V-max) than patients with only mild (n = 9) or moderate (n = 14) degrees of AI (Severe AI = 35.0 +/- 12.0 cm/sec, moderate AI = 16.8 +/- 3.9 cm/sec, mild AI = 7.4 +/- 2.6 cm/sec; p < 0.01) and also showed significantly higher values with regard to the time velocity integral of the regurgitant jet (severe AI = 13.8 +/- 5.6 cm; moderate AI = 5.7 +/- 2.4 cm, mild AI = 1.4 +/- 0.9 cm; p < 0.01). After classification by jacknife discrimination analysis, the Doppler ultrasound grading was compared with a corresponding three-point scale (mild, moderate, severe) from aortic root angiography. A correct estimation of the severity of AI was possible in 44 of 50 patients (88%; overestimation in one, underestimation in five) and in 41 of 50 patients (83%; overestimation in one, underestimation in eight) with regard to V max and the time velocity integral of the regurgitant jet, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481243 TI - Detection of proximal stenosis of left coronary artery by digital transesophageal echocardiography: feasibility, sensitivity, and specificity. AB - To assess feasibility, sensitivity, and specificity of transesophageal echocardiography (TEE) in visualizing proximal left coronary artery segments (entire left main, proximal left anterior descending, and circumflex) and in identifying proximal coronary stenosis, 160 consecutive patients were studied. Each patient underwent TEE before coronary angiography; the echocardiographic images were digitized and reviewed in a continuous cineloop format. The entire proximal left coronary artery was adequately imaged in 111 patients (70%). A stenosis was considered to be present at TEE if hyperreflecting plaques narrowing the coronary lumen were observed. TEE observed the presence of a stenosis in 6 of 6, 50 of 63, and 13 of 24 patients with stenosis detected at angiography on the left main, left anterior descending, and circumflex, respectively, and 2 of 105, 5 of 48, and 14 of 87 patients without angiographically detectable coronary stenosis in corresponding coronary segments. Thus, sensitivity and specificity of TEE in identifying stenosis of the left main coronary artery, proximal left anterior descending artery, and proximal circumflex artery were 100% and 98%, 79% and 89%, 54% and 84%, respectively. In conclusion, TEE identification of the proximal left coronary artery is feasible in most patients. Accuracy in identifying significant proximal stenosis varies from segment to segment and is higher for the left main coronary artery. PMID- 8481244 TI - Resolution limitations in intravascular ultrasound imaging. AB - Interest in the use of ultrasound to characterize the structure and composition of blood vessel walls has risen dramatically as a result of the development of intravascular ultrasonic imaging transducers mounted on the tips of small diameter catheters. A study of the resolution of these transducers is needed to understand the limitations in the visualization of these structures. Theoretic and experimental studies of the resolution of the two principal designs of intravascular ultrasonic transducers, the mechanically scanned single element and the multielement circular array, were carried out. Comparisons of the two designs reveal that they have similar resolutions. However, the resolutions in two of the three dimensions are shown to decrease linearly with increasing radial distance. Significant errors in image interpretation, particularly in larger diameter vessels, will result if this variation in resolution is not accounted for. PMID- 8481245 TI - Quantitation of the motion of the cardiac base in normal subjects by Doppler echocardiography. AB - Because the motion of the base of the heart plays a central role in its filling and emptying, we developed an original method to characterize the base motion dynamics throughout each cycle by use of pulsed Doppler echocardiography. A 100 Hz wall filter and low gain settings were used to record the low-frequency, high energy Doppler signals generated by the motion of the base. From the apical four chamber view, the sample volume was placed at the lateral margin and at the common septal margin of the tricuspid and mitral annuli. These signals were differentiated from left and right atrioventricular flows by their opposite direction, higher energy, timing, and unique audio signal. The dynamics of the cardiac base were quantitated in 17 normal subjects (31 +/- 13 years). The time relationship between transvalvular flows and the motion of the base was studied in nine normal subjects by matching recordings at the same RR interval. The Doppler signal of the motion of the cardiac base showed a succession of positive (apically directed) and negative (atrially directed) velocity waves. Differences in the dynamics of the cardiac base were demonstrated between its left and right components, probably related to different loading conditions and different myocardial mechanical properties. The relationship between the motion of the base and mitral flow as shown in this study suggests that Doppler-measured mitral flow velocity underestimates relative left ventricular inflow velocity with respect to the atrium by about 17% at peak early flow and by 20% at peak late flow. The method reported in the present study allows a more informative noninvasive quantitation of the cardiac base motion derived from measurements of its velocity, excursion, and acceleration. This new method may provide unique information on the left ventricular and right ventricular performance in the meridional direction. PMID- 8481246 TI - Supine bicycle stress echocardiography versus tomographic thallium-201 exercise imaging for the detection of coronary artery disease. AB - To compare the accuracy of supine bicycle stress echocardiography (SBSE), a new technique for evaluating coronary disease during peak exercise, with tomographic thallium-201 exercise imaging (SPECT), 71 patients were evaluated by SBSE, SPECT, and coronary arteriography. Twenty patients had normal coronary vessels; 22 had single-vessel, 14 had double-vessel, and 15 had triple-vessel disease. There were no differences in sensitivity (90% vs 92%), specificity (80% vs 65%), and accuracy (87% vs 85%) between SBSE and SPECT for the group of 71 patients. The results were similar in patients with and without prior myocardial infarction and with single-, double-, or triple-vessel disease. There were no differences between SBSE and SPECT for disease detection for the group of 213 individual vessels in sensitivity (88% vs 80%), specificity (87% vs 84%), and accuracy (88% vs 82%), but SBSE was more sensitive for the left anterior descending artery (97% vs 82%, p < 0.005) and for arteries involved in triple-vessel disease (93% vs 69%, p < 0.01) and more specific for the right coronary artery (88% vs 66%, p < 0.01). Supine bicycle exercise was associated with significantly lower maximal heart rates than treadmill exercise but with significantly higher systolic and diastolic blood pressures. There were no differences in heart rate x systolic blood pressure. We conclude that SBSE and SPECT are equally reliable for coronary disease detection in patients and for evaluation of disease in specific arteries with the exception of SBSE's higher sensitivity for the left anterior descending artery and arteries involved in triple-vessel disease and higher specificity for the right coronary artery. PMID- 8481247 TI - Detection of coronary artery disease with upright bicycle exercise echocardiography. AB - This study examined the advantages and limitations of upright bicycle exercise echocardiography in the evaluation of a large series of patients with known or suspected coronary artery disease. The study population consisted of 309 patients (231 men, mean age 57 +/- 11 years) who underwent exercise echocardiography within 8.5 +/- 16.1 days of coronary angiography. All stress electrocardiographic, echocardiographic, and angiographic data were reinterpreted in a blinded manner by the investigators. No patient was excluded because of poor echocardiographic image quality. Wall motion was analyzed at baseline, peak exercise, and immediately after exercise with a 16-segment model, and a regional wall motion score index was calculated at each stage. Abnormalities were ascribed to the distribution of the three coronary arteries and correlated with qualitative angiography. There were 126 patients with wall motion abnormalities at rest and 211 (75%) with coronary artery disease. The stress electrocardiogram (ECG) was negative in 61, positive in 144, and nondiagnostic in 104, yielding a sensitivity of 40% and a specificity of 89%. Echocardiography was normal in 76 of 98 patients without coronary disease (78% specificity) and abnormal in 193 of 211 patients with disease (91% sensitivity). Sensitivity was higher among patients with multivessel disease compared with those with single vessel disease (95% versus 86%, respectively, p = 0.03). Among patients with normal wall motion at rest (n = 183), sensitivity was 83% and specificity was 84%. Of the 104 patients with a nondiagnostic stress ECG, echocardiography correctly identified 95% of those with coronary disease and 75% of those without disease. Among 82 patients with a wall motion abnormality at rest, an additional exercise-induced wall motion abnormality developed in 32 of 46 patients (70%) with multivessel disease and seven of 32 (22%) with single-vessel disease. Overall, echocardiography detected 258 of 392 (66%) individual coronary lesions. Accuracy was higher for lesions in the left anterior descending and right coronary arteries (both 79%) compared with the left circumflex artery (36%, p < 0.001). In conclusion, upright bicycle exercise echocardiography is an accurate technique for the evaluation of patients with known or suspected coronary artery disease and is especially valuable in patients with a nondiagnostic stress ECG. The test provides supplemental information on the extent and location of coronary lesions and is useful in patients with and without prior myocardial infarction. PMID- 8481248 TI - Stress echocardiography: is there an optimal type of stress? PMID- 8481249 TI - A double-blind trial of glycopyrrolate for transesophageal echocardiography. AB - Glycopyrrolate is an anticholinergic agent used to dry oral secretions and has been advocated for routine use with transesophageal echocardiography (TEE). To evaluate the safety and efficacy of glycopyrrolate for this unique application, a prospective double-blind placebo-controlled study of glycopyrrolate was performed in 61 patients who were awake while undergoing TEE. Thirty patients were randomized to the standard dose of glycopyrrolate (0.2 mg intravenously), and 31 patients received 1 ml of saline solution as placebo. Intravenous midazolam was used for sedation in all but one patient. Heart rate, electrocardiogram, blood pressure, and oxygen saturation were continuously monitored before, during, and after TEE. The patients scored their comfort immediately after TEE and were interviewed at 24 hours for side effects. The operator scored the ease of performing the TEE. No complications occurred in either group. Changes in vital signs and oxygen saturation were similar in both groups. The operator ease and patient comfort was similar in both groups. A significantly higher incidence of the following side effects was observed at 24 hours in patients who received glycopyrrolate versus those who received placebo: sore throat, 63% versus 19%; dry mouth, 43% versus 6%; and urinary retention, 16% versus 0% (p < 0.05 for all). No benefit from glycopyrrolate was noted in operator ease or patient comfort. In conclusion, glycopyrrolate is not recommended for routine use when performing TEE on patients who are awake. PMID- 8481250 TI - Outpatient transesophageal echocardiography with intravenous propofol anesthesia in children and adolescents. AB - Outpatient transesophageal echocardiography (TEE) was performed in 10 children and adolescents (aged 3 to 19.5 years, mean 13.5 years; weight 12 to 91 kg, mean 49 kg), including two with Down's syndrome and one with autism, for diagnostic evaluation of issues unresolved by transthoracic echo examination (TTE). Issues for TEE: evaluation for atrial septal defect (two patients); anatomy of left ventricular outflow tract obstruction (one patient); aortic valve anatomy before valvuloplasty for insufficiency (one patient); evaluation for cause of cyanosis after Fontan operation (one patient); determination of source of high-velocity intracardiac turbulence after atrioventricular septal defect repair (one patient); rule out cardiac embolic source in patient with stroke (one patient); evaluate prosthetic valve function and rule out thrombus (one patient); determination of anatomic relationship of mitral valve to a ventricular septal defect before surgery for complex cyanotic heart disease (one patient); and evaluation for aortic dissection in Marfan's syndrome (one patient). Intravenous propofol anesthesia administered without endotracheal intubation by an anesthesiologist allowed successful outpatient TEE in nine patients; midazolam conscious sedation was used in one. Outpatient TEE resolved diagnostic issues in all patients without complication, thereby avoiding cardiac catheterization in six patients and supplementing catheterization for preoperative planning in four patients. TEE can be performed safely and effectively with propofol anesthesia in the outpatient setting in carefully selected children and adolescents to provide vital diagnostic information. However, given the invasive nature of the procedure and the use of anesthesia, outpatient pediatric TEE should be used judiciously. PMID- 8481251 TI - Problems in timing of respiration with the nasal thermistor technique. AB - When one analyzes transvalvular and venous flow velocity patterns, it is important to relate them to respiration. For this reason a nasal thermistor technique is often used, although it is known that this signal is delayed in relation to intrathoracic pressure changes. The magnitude and variation in delay have not been investigated previously and were, therefore, studied in a model experiment in 10 normal subjects, in 10 patients with obstructive, and in 10 patients with restrictive pulmonary disease. Esophageal pressure variations measured with an air-filled balloon served as a gold standard for intrathoracic pressure changes. During basal conditions there was, for both patient groups and normal subjects, a considerable delay of the thermistor signal. The average delay for all subjects was 370 msec with a wide variation (from 120 to 720 msec). At higher breathing frequencies the delay shortened to 310 msec (P < 0.01) but there was still a wide variation (ranging from 200 to 470 msec). Theoretic calculations show that the delay caused by the respiratory system accounts for only a minor portion of the total delay. Model experiments confirmed that the response characteristics of the thermistor probes limit the accuracy in timing of respiration. The total delay with the investigated thermistor technique is too long and variable to fulfil clinical demands. PMID- 8481252 TI - Aortic dissection complicating cardiac surgery: diagnosis by intraoperative biplane transesophageal echocardiography. AB - Aortic dissection is a rare but devastating complication of cardiopulmonary bypass. Intraoperative transesophageal echocardiography can be a useful technique to define the anatomy of the dissection, to evaluate its extension and progression, and to detect the presence of aortic insufficiency. We describe two cases in which transesophageal echocardiography helped in making a rapid diagnosis of aortic dissection during cardiac surgery and demonstrate how it may play a role in therapeutic decision making. PMID- 8481253 TI - Tricuspid flail leaflets after orthotopic heart transplant: a new complication of endomyocardial biopsy. AB - A case of tricuspid flail leaflets in a patient with orthotopic heart transplant is reported. The use of echocardiography to document the complication and its relationship to endomyocardial biopsy is presented. PMID- 8481254 TI - Optimal antithrombotic therapy following aortocoronary bypass: a meta-analysis. AB - To evaluate the role of antithrombotic therapy, on preserving graft patency, we performed a meta-analysis of randomized clinical trials involving aspirin (ASA), dipyridamole (D), anticoagulants (AC) and placebo or nontreatment controls (P). Manual literature searches were performed supplemented by computerized MEDLINE listings complete to July 1991. Saphenous vein graft occlusion was determined by angiography (patients with > or = 1 distal anastomotic occlusion). The trial data were aggregated with the methods of Mantel and Haenszel. The results are reported as odds ratios (OR) +/- 95% confidence intervals (CI). Seventeen trials were evaluated. Aspirin strongly influenced graft occlusion [ASA +/- D vs P: OR 0.60, 95% CI 0.51, 0.71, P < 0.0001], but dipyridamole provided no additional benefit [ASA+D vs ASA: OR 0.94, 95% CI 0.72, 1.24, P = 0.71]. Anticoagulants reduced graft occlusion [AC vs P: OR 0.56, 95% CI 0.33, 0.93, P = 0.025] and the results were similar to that achieved with aspirin [ASA vs AC: OR 0.95, 95% CI 0.62, 1.44, P = 0.87]. The combination of aspirin and anticoagulants was superior to anticoagulants alone in two limited trials [ASA+AC vs AC: OR 0.55, 95% CI 0.33, 0.88, P = 0.01]. A low (100 mg) to medium (325 mg) daily aspirin dosage was more effective than a high dose (975 mg). Early postoperative treatment (< or = 6 h) strongly influenced graft occlusion while preoperative administration provided no additional benefit. No mortality advantage was identified for any antithrombotic therapy. Aspirin or anticoagulants enhance saphenous vein graft patency following aortocoronary bypass surgery, and a combination thereof deserves further investigation in a trial large enough to detect the effects of these treatments with respect to clinical events. PMID- 8481255 TI - Lowered threshold for ventricular fibrillation in amiodarone-treated pigs undergoing cardiopulmonary bypass and cardioplegic arrest with St. Thomas' cardioplegic solution. AB - The antiarrhythmic agent amiodarone has been suspected of causing reduced cardiac performance after extracorporeal circulation and cardioplegic arrest in patients. This has recently been confirmed in an experimental model where pigs were exposed to cardiopulmonary bypass and cold cardioplegic arrest with Bretschneider's solution. Due to the high concentration of the cardio-depressant agent procain in Bretschneider's solution, it could be speculated whether it is the combination of amiodarone and this solution that may be potentially deleterious, rather than amiodarone alone. To investigate this, adult pigs (75 +/- 2 kg at surgery) were treated with amiodarone for 30 +/- 2 days (1400 mg/day: n = 8, untreated controls: n = 4, blind experiment), followed by exposure to cardiopulmonary bypass with universal cooling to 28 degrees C and topical cold cardioplegic arrest with St. Thomas' solution for 60 min. Apart from 1 g of calcium (Ca2+) at the end of bypass, no inotropic drugs were administered. Cardiac reserve was tested by right ventricular pacing (200 beats/min until death or up to 30 min). The two groups did not differ concerning preload or afterload, heart rate, cardiac output, left ventricular pressure, arterial pressure or rate of change in left ventricular relaxation (-dP/dt) before or after bypass was terminated, while the rate of change in left ventricular contraction (+dP/dt) was lower in the amiodarone-treated pigs. The time on bypass, before stable hemodynamics had recovered, was prolonged in amiodarone-treated animals, 46 +/- 4 min versus 31 +/ 3 min in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481256 TI - Alterations of cell-mediated immune response following cardiac surgery. AB - Nosocomial infections in patients following cardiac surgery are frequently associated with opportunistic microorganisms indicating a dysregulation of cell mediated immune response. The objective of this prospective randomized trial, therefore, was to investigate the mechanisms of dysregulation and the counterregulatory effects of immunomodulation. Twenty patients underwent conventional postoperative therapy, another 20 patients received indomethacin, which inhibits synthesis of the down-regulating mediator prostaglandin E2, and a further 20 patients were given thymopentin in addition to indomethacin, thereby augmenting activation and differentiation of the T-lymphocytes. The immunologic parameters studied included T-lymphocytes and monocytes as well as interleucin (IL)-1 and IL-6 synthesis by monocytes, and IL-2 and IL-6 synthesis by T lymphocytes. Following cardiac surgery a significant, persistent reduction of T lymphocytes and IL-2 synthesis as well as significant monocytosis could be observed. Indomethacin treatment resulted in a normalization of the cellular imbalance at the end of the first postoperative week, but IL-2 synthesis remained significantly reduced during the entire observation period. Conversely, with combined indomethacin and thymopentin treatment restoration of cellular distribution as well as protection of IL-2 synthesis could be achieved. These results indicate a quantitative and functional impairment of the forward regulation of cell-mediated immunity. It was shown for the first time that combined indomethacin and thymopentin treatment could successfully counteract these immunomechanistic alterations. PMID- 8481257 TI - High incidence of aneurysm formation following patch plasty repair of coarctation. AB - Repair of aortic coarctation was performed in 152 adolescent and adult patients (mean age 28.5 years, range 14-67 years). Ninety patients were treated with patch plasty, 33 with end-to-end anastomosis, 18 with interposition of a tubular graft, 6 with prosthetic bypass and 5 with direct plasty. There were two (1.3%) early and ten (6.6%) late deaths after 2.9 to 11.8 (mean 6.6) years. Of the remaining 140 patients, 129 (92.1%) were reexamined with computed tomography and angiography after 1.5 to 17.2 (mean 9.1) years postoperatively. In 27 patients (35.1%) of the patch plasty group significant dilatation at the operative site was observed and reoperation for aneurysm formation was required in 15 patients (19.5%). Resection of the intimal crest did not increase the probability of aneurysm formation, whereas Dacron as patch material and late hypertension had a significant influence. Six of the ten late deaths occurred in the patch plasty group. Rupture of an aneurysm at the operative site was proved in two of these patients, and three patients died suddenly for unknown reasons. In the other groups significant dilatation was observed in 13 patients and 3 local aneurysms required reoperation (2 after end-to-end anastomosis and 1 after direct plasty). We conclude that patch plasty repair of coarctation should be abandoned in adults. End-to-end anastomosis is advisable only if possible without excessive tension. Reoperation with interposition of a tubular graft on left heart bypass proved to be a safe method. PMID- 8481258 TI - Early results of intravascular oxygenation. AB - We have used the intravascular oxygenator (IVOX) in eight patients (14-76 years) with acute respiratory failure. At the time of referral for IVOX all patients were on inotropic support, five had pneumothoraces and two were on haemofiltration. Ventilatory data before IVOX were: ventilated for 2-14 days (median 6), PEEP 5-12 cm H2O (12), PIP 34-95 cm H2O (49), FiO2 0.7-1 (1), PaO2 5.4-26 KPa (8.5) and PaCO2 3.7-23 KPa (8). The intravascular oxygenator was used for 6 h-12 days (median 4), the oxygen transfer achieved was 68-140 ml/min (85) and the carbon dioxide removed was 40-106 ml/min (59). It was possible to decrease the ventilator settings with a significant increase in the PaO2 by 48 h (P < 0.05) but the fall in PaCO2 did not reach significance. As the IVOX was turned from "off" to "on" the mean PaO2 increase was 0.35 KPa +/- 0.14 SEM (P = 0.04) and the mean PaCO2 decrease 0.7 KPa +/- 0.2 SEM (P = 0.02) without any significant change in cardiac output. Two patients survived and six died from multisystem failure with three patients being hypoxic at the time of death. Postmortem examinations on five patients did not reveal any IVOX-related complications. We conclude that IVOX is safe but it is not as efficient in gas exchange as extracorporeal membrane oxygenation at present. Further improvement in the gas exchange efficiency of this prototype could render IVOX a very useful device. PMID- 8481259 TI - Antiplatelet therapy in children with left-sided mechanical prostheses. AB - Valve replacement in children has always been associated with a high mortality, outgrowth of the prosthetic valve and difficulty in managing anticoagulation. Between January 1985 and April 1991, 20 patients (14 males and 6 females) underwent replacement of a left-sided cardiac valve. The median age at diagnosis was 21.6 months (1 to 120 months) and the median age at surgery was 85 months (11 to 213 months). Six patients were under 4 years of age. The site of valve replacement was aortic in 11 patients and left atrioventricular (AV) valve in 9 patients. The indications for aortic valve replacement were stenosis (6) and incompetence (5). The left AV valve was replaced in three patients following repair of AV septal defect, in one patient with corrected transposition of the great arteries (LTGA), in one patient with severe dysplasia and insufficiency, and in four patients for congenital mitral stenosis. A Bjork-Shiley prosthesis was used in three mitral and one aortic position, all the other patients receiving a St. Jude prosthesis: six mitral and ten aortic. All patients were anticoagulated (warfarin) for 3 months post implantation and then switched to a regimen of aspirin and persantine. There was no early or late death. Median follow-up was 12.3 months (4 to 72 months). Total follow-up was 59 patient-years or 708 months. There was one incident of thromboembolism (1.7%/patient-year) and four instances of bleeding (6.8%/patient-year). There was no valve thrombosis. Our regime of early warfarin followed by long-term antiplatelet therapy has been associated with a low incidence of thromboembolism and no valve thrombosis. PMID- 8481260 TI - Incidental lung adenocarcinoma in a 20-year-old woman with bronchiectasis. AB - A case of lung adenocarcinoma in a 20-year-old woman with bronchiectasis is presented. The patient showed no clinical and radiological findings in regard to the carcinoma. The tumor was discovered incidentally in the parenchyma of the lung specimen resected due to chronic bronchiectasis. PMID- 8481261 TI - Castleman's disease arising from the intercostal space. AB - A 27-year-old woman was investigated for a tumour of the posterior chest wall. This was excised surgically and histologically it proved to be a hyaline vascular type of angiofollicular lymphoid hyperplasia or Castleman's disease. This is the third case from the literature of such a tumour arising from the intercostal space. Surgical excision has been proved curative until now with no recurrence. PMID- 8481262 TI - Coronary artery anastomotic contour--a method for individual surgeons to assess their suture techniques. AB - A method is described whereby individual surgeons may monitor their coronary graft suturing techniques. The coronary artery anastomotic contour is measured quantitatively in corrosion resin cast models made of anastomoses between long saphenous vein and the left anterior descending coronary artery of a pig's heart. The relevant parameter assessing the contour is the mean anastomotic narrowing expressed as a percent (MAN%). To provide an example of the potential of the method, a single surgeon compared a continuous suture technique (n = 30) with an interrupted one (n = 30) using corrosion resin models. There was significantly less (P < 0.05) narrowing of the anastomotic contour with the interrupted technique (mean MAN% = 0.3 +/- 2.9) than with the continuous (mean MAN% = 10.5 +/ 3). PMID- 8481263 TI - Magnetic resonance imaging of vascular rings. PMID- 8481264 TI - Choroid plexus cysts: significance and current management practices. AB - Choroid plexus cysts are commonly found in normal fetuses in the second trimester, but the presence of cysts is an indication for a targeted ultrasound scan for signs associated with aneuploidy. In this review the authors explain the histological basis for choroid plexus cyst formation, the association with aneuploidy, and the management controversies that continues to be debated in the literature. PMID- 8481265 TI - Routine ultrasound surveillance of the pregnant uterus. AB - The routine ultrasound examination of the pregnant uterus is presented in this article. The approach is based on published guidelines, dividing the examination into studies of the first trimester and studies of the second and third trimesters. The discussion emphasizes the standard anatomical views and describes the normal sonographic appearances. The methods of obtaining important measurements are described, and tables are provided to analyze these measurements. A systematic approach to obstetric ultrasound is important in ensuring completeness and in maximizing the detection of fetal abnormality. PMID- 8481266 TI - Amniotic fluid volume: fluid dynamics and measurement technique. AB - Evaluation of amniotic fluid volume is an important aspect of obstetrical ultrasound. Several methods are currently used to describe amniotic fluid volumes. The most common are the subjective assessment of fluid and the semiquantitative methods. The reproducibility of these methods is excellent in experienced hands. Because of the multiple methods used to assess fluid, both oligohydramnios and polyhydramnios have numerous definitions. Regardless of which definition is used, it is clear that both of these entities are associated with a variety of fetal and maternal conditions. Abnormal amniotic fluid volume may be the only or earliest sonographic sign of an obstetrical problem. Therefore, it is important that sonologists are familiar with amniotic fluid volume assessment. Although subjective and semiquantitative techniques may produce similar results, a numerical scale is no substitute for experience and training. One should be able to recognize lesser degrees of fluid abnormality and be able to assess the trend of amniotic fluid volume in serial examinations. PMID- 8481267 TI - Twin growth problems: causes and sonographic analysis. AB - Understanding the significant increased risks associated with twin pregnancies requires knowledge of the embryogenesis of twins and the unique placental characteristics seen only in twin gestations. Dizygotic "fraternal" twins, 70% of all twins, are at relatively low risk when compared with monozygotic twins, largely due to abnormalities seen in association with monochorionic placentation. The sonographic determination of chorionicity and amnionicity allows better estimation of pregnancy risk--up to 50% mortality in monochorionic-monoamniotic twins. Careful evaluation of intrauterine twin growth assists in the early identification of fetal abnormalities because normal twin growth should parallel that of singleton pregnancies until late in the third trimester. A number of the unique complications affecting growth in twin pregnancies are discussed, including twin transfusion syndrome, the "stuck twin" phenomenon, twin embolization syndrome, and development of acardiac twins. PMID- 8481268 TI - Condom use among high-risk women in Honduras: evaluation of an AIDS prevention program. AB - In 1988, the Honduran Ministry of Health initiated an intervention study designed to increase AIDS awareness and promote preventive behavior, especially condom use, among registered commercial sex workers (CSWs). The program consisted of weekly talks and free condom distribution to all CSWs who attended the sexually transmitted disease clinic during a 10-week period. Pre- and postintervention surveys were used to evaluate change in knowledge and condom use. Condom diaries were used to measure condom use during the program. One hundred thirty-four women who participated in the intervention completed the initial and follow-up surveys. There was a statistically significant increase in mean condom use from 64% to 70% of client contacts. Condom use recorded in diaries during the program period appeared even higher. Factors found to be associated with increased use postintervention include low baseline condom use and higher client fee. The reliability of the methods of measuring condom use and the implications of the findings for future intervention studies among sex workers and their clients are discussed. PMID- 8481269 TI - Sexual risk for HIV transmission among gay/bisexual men in substance-abuse treatment. AB - A sample of San Francisco gay/bisexual men in substance-abuse treatment (N = 314) was compared to the San Francisco Men's Health Study (SFMHS) cohort to compare levels of sexual behaviors that are high-risk for HIV transmission. Quantitative data were supplemented by analysis of transcripts of focus group discussions with gay men in treatment at the same agency. Sexual risk for HIV infection was significantly higher for gay/bisexual men in substance-abuse treatment than among the community-based (SFMHS) sample of gay/bisexual men. Among those entering outpatient alcohol/drug treatment, 21% reported unprotected insertive and sex, 23% reported unprotected receptive anal sex, and 32% reported unprotected insertive and/or receptive anal sex during the previous 3 months. In comparison, in the SFMHS cohort, 17% reported unprotected insertive and sex, 15% reported unprotected receptive anal sex, and 22% reported unprotected insertive and/or receptive anal sex during the previous 6 months. Substance abusers in focus groups identified a number of factors that made it difficult to reduce their sexual risk behavior, including the perceived disinhibiting effects of alcohol and other drugs, learned patterns of association between substance use and sex (especially methamphetamine use and anal sex), low self-esteem, lack of assertiveness and negotiating skills, and perceived powerlessness. PMID- 8481270 TI - A contextual model of stress among parent caregivers of gay sons with AIDS. AB - This paper examines the impact of AIDS on the parent/adult child relationship among parent caregivers of gay sons with AIDS. Drawing on literature on family caregiving of older people and research on parents of gay sons with AIDS, the theoretical concepts of family ethos of affection/obligation, attitudes toward homosexuality, and stress are reviewed. Based on these key theoretical concepts and linkages, a model is developed that suggests the family characteristics that differentiate low-stressed parent caregivers and high-stressed parent caregivers. A case study is presented to illustrate the model. Recommendations for research and implications for professionals are discussed. PMID- 8481271 TI - Perceptions of vulnerability: impact on AIDS-preventive behavior among college adolescents. AB - Perceptions of their own and others' risk of contracting AIDS, AIDS knowledge, and extent of AIDS-preventive behavior (APB) were assessed in sexually active heterosexual college students (N = 80) to investigate why many college students fail to enact APB. Personal risk of contracting AIDS was estimated to be significantly lower than risk for each of a set hypothetical persons who varied in degree of similarity to respondents, p < .0001. ANOVAs indicated that males (F = 60.13, p < .0001), homosexual males and females (F = 62.55, p < .0001), and young adults not in college (F = 8.17, p < .005) were perceived as more likely to contract AIDS than females, heterosexuals, and college students, respectively. AIDS knowledge was related to accuracy of risk estimates, but was not predictive of APB. Lack of APB is discussed in terms of illusion of unique invulnerability and the characterization of AIDS as an outgroup problem. Implications and recommendations for AIDS-preventive education programs are discussed. PMID- 8481272 TI - Knowledge and attitudes about AIDS among staff of community-based health and social service organizations in the Southwest: implications for staff training. AB - To ascertain the specific AIDS training needs of staff from community-based organizations in the Southwest, a survey of knowledge and attitudes was conducted by the National Coalition of Hispanic Health and Human Services Organizations (COSSMHO) in the 5 Southwestern cities of Albuquerque, El Paso, Phoenix, San Diego, and Tucson. The responses of 1057 staff were examined according to staff position: managerial, direct service, clerical, and volunteer. Staff were 60.3% Hispanic/Latino and 28.4% white non-Hispanic. Staff responses were examined on 3 dimensions of AIDS-related knowledge and on 3 attitudinal dimensions. A multivariate analysis of covariance (MANCOVA) that controlled for 4 sources of group nonequivalence revealed generally that managers and direct service staff had higher knowledge and more favorable attitudes than did clerical and volunteer staff. Of greatest concern, however, was the number of specific knowledge items for which all staff obtained less than 80% correct answers. Disturbing knowledge deficits exist on important AIDS-related information across all levels of staff. Specific content and strategies are presented for corrective interventions by staff type. PMID- 8481273 TI - The role of family therapy in decreasing HIV high-risk behaviors among adolescents. AB - Adolescence is a critical time for the prevention of human immunodeficiency virus (HIV) infection and both the prevention and treatment of high-risk-for-HIV behaviors such as drug abuse and unprotected sex. Family therapy appears to be a promising, yet neglected, source of influence in the prevention of HIV. In this paper, the authors identify HIV risk factors among adolescents and provide a rationale for the use of family therapy to prevent high-risk-for-HIV behaviors among adolescents. Also included are the components of one promising family therapy model for addressing risk reduction in adolescents. An illustrative case example is provided. PMID- 8481274 TI - First Asian/Pacific Island Men's HIV Conference, Los Angeles, California. PMID- 8481275 TI - [PTFEe in the treatment of facial wrinkles]. AB - The first signs of skin aging appear quite early, around 30 years of age, and show as glabella and facial wrinkles particularly pronounced around the eye, lips and nasolabial area. None of these imperfections can be expressively modified through a cervicofacial rhytidectomy (facelift). The use of PTFEe in reconstructive surgery has been established by years of positive experience; therefore, the well known characteristics of such material suggested the idea of extending its use to aesthetic surgery. The corrections performed with this material are carried out mostly as day hospital surgery in local anaesthesia, requiring, however, technical skill to obtain satisfying results. PMID- 8481276 TI - [The diagnostic and therapeutic strategies in neoplasms of the adrenal cortex: the authors' own experience]. AB - The Authors report their limited series of neoplasms of the adrenal cortex, and underline the decisive role of the modern diagnostics based on imaging techniques (US--TC--NMR). These, in fact, often allow a good definition also in the non functioning adrenal masses incidentally discovered (incidentalomas). The authors emphasize the high quality of such diagnostic methods offering a good reliability in discriminating the nature of the adrenal mass. These undeniable diagnostic advantages have a positive impact on the surgical strategy, allowing together with a careful morphological study of the lesion, to program in detail possible demolitive operations. The authors finally underline the importance of the surgical access: they are persuaded the best is the bilateral under-rib incision. This surgical approach assures a complete exploration of the abdominal and pelvic cavity; moreover, it allows to face every complication. PMID- 8481277 TI - [Isolated unilocular hydatidosis of the kidney: a rare clinical event]. AB - The authors report a case of granulomatous hydatid disease of the kidney recently observed in a 47-year-old female patient with a preoperative diagnosis of nephrolithiasis. The rarity of the location and the likely asymptomatic nature of the disease are, in the authors opinion, of clinical and scientific interest. PMID- 8481278 TI - [Malignant mesothelioma located in the pleura: its radical surgical treatment]. AB - The authors report a rare case of localized malignant pleural mesothelioma infiltrating the thoracic wall. The absence of widespread pleural involvement allowed for a radical operation with removal of a large portion of the thoracic wall. However, due to rarity of such tumor, an hypothesis on long term prognosis is difficult to formulate. PMID- 8481279 TI - [The surgical treatment of a differentiated thyroid carcinoma infiltrating the large mediastinal veins]. AB - The authors report on 2 patients affected by well-differentiated, locally advanced, thyroid carcinoma infiltrating the major mediastinal veins. Removal of the neoplastic mass was possible through a combined cervical and trans-sternal approach. Surgical indication, operative strategy and follow up are discussed. A review of the literature is also reported. PMID- 8481280 TI - [Juvenile vascular pathology due to homocystinuria. A clinical case report]. AB - The authors report a case of juvenile vasculopathy in a homocystinuria patient. They point out that thromboembolism may be the only symptomatic expression of this genetically determined metabolic disease. Diagnostic approach and surgical therapy of the vascular lesions as well as medical therapy to prevent further complications are analysed. The opportunity to perform clinical tests for the diagnosis of homocystinuria in all those young patients presenting vascular lesions without other risk factors is finally stressed. PMID- 8481281 TI - [Intestinal obstruction due to phytobezoars]. AB - The authors report nine cases of small bowel obstruction due to phytobezoars, observed from January 1982 to October 1991. The main factors in the pathogenesis of phytobezoars, particularly alimentary habits and previous gastric surgery, are considered. In five patients the operation, always performed in emergency, consisted in a longitudinal enterotomy. In two cases the plasticity of the phytobezoar allowed for a manual progression beyond the ileocecal valve. In two patients an intestinal resection was necessary. The authors prefer the finger fracture technique with manual progression of the phytobezoar beyond the ileocecal valve when the ileal loop is well conserved and the phytobezoar itself has enough plasticity. PMID- 8481282 TI - What is the future of biliary surgery? PMID- 8481283 TI - [Loco-regional anesthesia in the surgery of inguinal and crural hernias. The authors' own experience with 1730 treated cases]. AB - The authors report their experience with the use of loco-regional anaesthesia for the surgical treatment of inguinal and femoral hernias. Their series includes 1730 operations, 235 of which for hernia relapses, performed exclusively in the outpatient department. In the authors opinion, with loco-regional anaesthesia it is possible to treat any type of inguinal-femoral hernia, reducing the risks related to total anaesthesia and the complications arising from bedrid. Excellent results were achieved especially in the elderly and high risk patients like cardiopathic or those affected by respiratory and hepatorenal insufficiency with a complete absence of mortality and morbidity. PMID- 8481284 TI - [Intermittent electromechanical dissociation of the internal anal sphincter in idiopathic fecal incontinence]. AB - Ten patients with median age of 51 years (range 24-75; 9 female) presenting idiopathic faecal incontinence and twelve normal subjects with median age of 34 years (range 25-71; 5 female) underwent fine wire anal sphincter electromyography and anal manometry. The results were analysed using non-parametric methods of statistical analysis. The median IAS EMG was 0.30 Hz (range 0.18-0.38), in incontinent and 0.48 Hz (range 0.31-0.55) in controls; p. < 0.01. Ambulatory resting pressures were a median of 66 cmH2O (range 49-83 cmH2O), for the incontinent and 82 cmH2O (range 66-120) for controls; p < 0.04. IAS EMG frequency correlated with resting anal pressures in both groups (p < 0.003). IAS EMG silence not attributable to electrode movement or to the recto-anal inhibitory reflex, lasting 0.5-4 minutes, occurred in all but two of the incontinent patients. No recruitment of the external sphincter or puborectalis muscle was noted during these episodes. Such electromechanical dissociation was not seen in the control group. PMID- 8481285 TI - [Anatomicosurgical research on isolating the retrohepatic segment of the vena cava inferior]. AB - The retrohepatic segment of the inferior vena cava is considered of major importance in the surgical management of both thoracoabdominal trauma and neoplasms involving the venous wall. Twenty autopsies and 10 anatomical specimens were employed to examine the patterns of the avascular inter-hepato-caval median space. For the isolation and ligation of the hepatic veins a rubber snare was inserted into the avascular plane assuring a right tension of the vasculo parenchymal lamina which attracts the liver to the vena cava. The number and the course of the hepatic veins were clearly identified. Authors' experience, coupled with a critical review of the literature, confirms that successful isolation of the believed surgically inaccessible retrohepatic vena cava and hepatic veins may represent a suitable approach for major injuries or neoplasias of these structures. PMID- 8481286 TI - Medical consultations for asthma attacks, 1988-1991. PMID- 8481287 TI - New immune system vaccines to be tested. PMID- 8481288 TI - Test could reveal HIV infection in newborns. PMID- 8481289 TI - Protecting the consumer. PMID- 8481290 TI - Spurious connection or real risk? PMID- 8481291 TI - Sponsorship: seen to be above suspicion. PMID- 8481293 TI - Nurses work. Life after redundancy. PMID- 8481292 TI - Sex on the ward. PMID- 8481294 TI - Nurses work. Why counsel? PMID- 8481295 TI - Therapeutic risks in mental health nursing. AB - Taking risks would appear to be a part of everyday life for most people, but this is not always the case for many long-stay psychiatric patients. Nurses frequently over-protect people receiving mental health care because they are concerned that the patient may come to harm. Allowing patients to take therapeutic risks which can help them to learn from their mistakes can be extremely beneficial. This article outlines the importance of incorporating safeguards into the care plan to ensure the risk of harm is minimised. PMID- 8481296 TI - Delaying attendance at A&E departments. AB - In the first article of a new four-part series, Mike Walsh analyses the reasons why patients delay before attending an accident and emergency (A&E) department. Interviews with a sample of 200 A&E patients were conducted to find out why people attend when they do. Factors such as presence of a wound, access to the department and type of condition were found to be significant in their decision. The concepts of utilisation time, illness time and appraisal time are essential in understanding why patients may delay their attendance. Subsequent articles will address questions such as why people attend A&E rather than their GP, pain and anxiety in A&E, and patients' opinions of their experience. PMID- 8481298 TI - Achieving a healthy working environment. PMID- 8481297 TI - Open learning for enrolled nurses. AB - Within the new market economy of the NHS, it is necessary to provide reliable information on the viability of educational initiatives which are planned, implemented and evaluated in an economic manner without compromising quality. The Sheffield and North Trent College of Nursing and Midwifery offers a unique opportunity for enrolled nurses who wish to retake first level nursing examinations. An evaluation of the course was undertaken which revealed that 75 per cent of the students felt the course had enhanced their personal study skills and professional awareness. PMID- 8481299 TI - Lateral nursing: nursing muddles. PMID- 8481300 TI - The pro-am debate. PMID- 8481301 TI - Worst among equals. PMID- 8481302 TI - The Clay column. PMID- 8481303 TI - Migraine: not just a headache (continuing education credit). PMID- 8481304 TI - Diabetes care: dispelling the myths (continuing education credit). PMID- 8481305 TI - New combinations beat HIV in vitro. PMID- 8481306 TI - Not playing God. PMID- 8481307 TI - A colour-blind health service. PMID- 8481308 TI - Food for thought. PMID- 8481309 TI - Employment law: the tender trap. PMID- 8481310 TI - Satisfaction with pay: changing nurses' pay. PMID- 8481311 TI - Nurses work--cost effectively. PMID- 8481312 TI - Nurses work. More nurses are needed. PMID- 8481313 TI - Nurses work. Age before duty. PMID- 8481314 TI - Epilepsy (continuing education credit). PMID- 8481315 TI - Computerised care plans in Tayside. AB - The development of ward nursing information systems and, in particular, the advent of computerised nursing care plans, have caused some controversy and discomfort in professional circles. This article describes how staff in a large general hospital in Tayside set about refining their information technology base, with particular emphasis on the role of the project nurse who had overall responsibility for the implementation of the programme. Despite cautionary words from some commentators, it appears that the computerised care planning module has been received positively by nursing staff. PMID- 8481316 TI - Pain and anxiety in A&E attenders. AB - Little research has been carried out into pain and anxiety in the A&E department. In the third article in this series, a study of 200 patients is described which revealed that only a small number of A&E patients reported having no pain or anxiety while substantial numbers were reporting high pain and/or anxiety levels. A statistically significant linkage between high pain and anxiety levels was demonstrated. The author reviews what factors cause anxiety and fear in patients attending A&E and concludes that nurses can alleviate worry and pain by better communication. PMID- 8481317 TI - Sister Susie. Multiskilling and other hot air. PMID- 8481318 TI - Ivory towers of strength. PMID- 8481320 TI - The Standard guide to achieving change quietly. PMID- 8481319 TI - Bullying: I fought back. PMID- 8481321 TI - Call for urgent review of HIV guidelines for health workers. PMID- 8481322 TI - Hepatitis A & B: the nurse's role (continuing education credit). PMID- 8481323 TI - Fats of life (continuing education credit). PMID- 8481324 TI - [The acute abdomen]. PMID- 8481325 TI - [Poisonous and less poisonous plants]. PMID- 8481326 TI - [History of alcoholic embryopathy. Historical sources in the visual arts and in literature]. PMID- 8481327 TI - [Analysis of the activities of pediatric nurses in a neonatal intensive care unit -study at the county children's hospital in Linz]. PMID- 8481328 TI - [Viral pneumonia and respiratory distress syndrome in an infant]. PMID- 8481329 TI - [Maternal protection legislation: Employer may request examination to prove work prohibition]. PMID- 8481330 TI - [Working time in the hospital: the union has the right to determine the working hours]. PMID- 8481331 TI - [Franz von Rinecker (1811-1883)]. PMID- 8481332 TI - [Perceptual disorders?]. PMID- 8481333 TI - [Tick bites; health risks]. PMID- 8481334 TI - Diagnosis and treatment of 17-hydroxylase deficiency. AB - Leading symptoms of 17-hydroxylase/17,20-lyase deficiency in childhood are hypertension and hypokalemia. We found this enzyme defect in 3 phenotypically female siblings aged 12, 15 and 16 years. Two of the sibs have a 46,XY chromosome pattern, the third is genetically female. Pubertal development did not occur. Both of the 46,XY sibs have male internal and female external genitalia. The 46,XX sister has normal female internal genitalia. At the time of diagnosis, two of the three siblings had hypertension (RR between 190/135 and 160/110 mmHg). Two of the three siblings had low serum potassium and metabolic alkalosis. All three patients had excessively high plasma levels of 11-deoxycorticosterone (DOC) and corticosterone. Aldosterone was also elevated whereas plasma renin activity was suppressed. Plasma cortisol and its 17-hydroxylated precursors were low, as were plasma testosterone, dihydroepiandrosterone sulphate and estradiol, while the gonadotropins LH and FSH were elevated in all three patients. We studied the steroid profiles of these three patients during long term glucocorticoid treatment with dexamethasone, which is now followed for 13 years. Blood pressure and serum potassium became normal. Plasma aldosterone, corticosterone and DOC were clearly lower but not fully normalized. The two genetically male sisters obtained estrogens for induction of female secondary sex characteristics. The third 46,XX sister has normal menstruations during substitution with cyclic estrogen/gestagen therapy. All three patients lack pubic and axillary hair, and reached normal adult heights both for phenotypic sex and for target height. The psychosocial orientation is female in all of them. Apart from rare reports of development of malignant hypertension, prognosis is better than in other enzyme deficiencies causing congenital adrenal hyperplasia since no Addisonian crises occur due to DOC and corticosterone overproduction resulting in apparently normal endogenous glucocorticoid activity. PMID- 8481335 TI - The pathogenesis of adrenal and extra adrenal hyperandrogenism. AB - The data reviewed in this paper suggest that a factor other than ACTH which is suppressible by treatment with glucocorticoid, plays an essential role in the regulation of adrenal androgen production. Adrenal androgen biosynthesis probably takes place exclusively in specific androgen-secreting cells. That availability of androgen substrate alone e.g. 17OH-progesterone, is not sufficient to lead to hyperandrogenaemia is clear from data which was obtained from treated patients with the 21 hydroxylase deficiency type of congenital adrenal hyperplasia. In pituitary ACTH excess, cortisol production is relatively greater than that of androgens. In contrast, in some patients with ectopic ACTH production, the excess production of androgens is relatively greater than that of cortisol. Taken together, these observations suggest that a factor closely related to ACTH, i.e. a POMC fragment other than ACTH, plays an important role in the regulation of adrenal androgen production, that in Cushing's disease the ratio of ACTH to the androgen-stimulating fragment increases, and that in some patients with ectopic ACTH syndrome the ratio of ACTH to the alternative fragment may be decreased. In addition, the data reviewed are consistent with a model for the pathogenesis of idiopathic hirsutism and polycystic ovary syndrome whereby mild adrenal androgen excess is primary to the development of these disorders. However, the identity of the putative adrenal androgen stimulating hormone has yet to be established. PMID- 8481336 TI - Partnership and sexuality in adult female patients with congenital adrenal hyperplasia. First results of a cross-sectional quality-of-life evaluation. AB - In congenital adrenal hyperplasia affected female patients are born with ambiguous genitalia caused by prenatally elevated circulating androgens from the defective adrenal glands. Surgical correction and life-long medication is needed to enable a normal female life. In contrast to androgen-related behaviour little information is available regarding the psychosocial consequences of genital malformations and lifetime medical treatment on the life of female patients. We report the results regarding partnership and sexuality of a comprehensive quality of-life evaluation of female patients with congenital adrenal hyperplasia. While there was no significant difference in the first overall evaluation between the various clinical forms of congenital adrenal hyperplasia, patients differed significantly from healthy controls in regard to partnership and sexuality. However, overall analysis suggested, that the patients were able to adjust well to their condition and were able to lead a normal life. Further longitudinal research is needed to more clearly identify problem areas and to improve medical and psychological treatment. PMID- 8481337 TI - Mass spectrometry in the diagnosis of steroid-related disorders and in hypertension research. AB - The use of GC/MS and microbore HPLC/electrospray mass spectrometry for clinical studies in hypertension and mineralocorticoid research is described. In particular, an automated GC/MS method allows nearly quantitative measurements of metabolites of major steroids of adrenal, placental and gonadal origin. This method is able to distinguish almost all steroid related disorders. Electrospray mass spectrometry in conjunction with microbore HPLC is the latest mass spectrometry technique applicable to biochemical investigations. It offers high sensitivity (15 pg) for measurement of intact steroid conjugates and related compounds. PMID- 8481338 TI - 19-Nor-corticosteroids in genetic hypertension. Effects of inhibitors of 11 beta, 18, 19-hydroxylase activity. AB - The long-term objective is to understand the role of the adrenal in altering systemic arterial blood pressure. This paper summarizes research on genetic hypertension in the rat and bears a relationship to several forms of human hypertension in which defects of steroid hydroxylases lead to increased secretion of mineralocorticoids other than aldosterone in genetic and experimental hypertension in rats. We demonstrated that 19-nor-corticosteroids are produced in excess in genetic and experimental hypertension in rats and man. We studied the enzymatic alteration responsible for excessive production of 19-nor deoxycorticosterone (19-nor-DOC) in the salt-sensitive hypertensive rat S/JR. Biosynthesis of 19-nor-steroids involves hydroxylation of the C-19 methyl group. We characterized the adrenal 11 beta, 18,19-hydroxylase enzyme system in inbred salt-sensitive and resistant rats (R/JR). This system is capable of all three hydroxylations. The Km for 19-hydroxylation was different from S/JR and R/JR but was much greater for 11 beta- and 18-hydroxylation in both. This suggested that the catalytic site for 19-hydroxylation is different from that for 11 beta and 18. The S/JR adrenal enzyme binds the substrate with higher affinity than does the R/JR adrenal enzyme. We were unable to distinguish the cDNAs of the S/JR from the R/JR adrenal enzyme from bovine 11 beta-hydroxylase cDNA by restriction mapping. We were unable to demonstrate restriction length polymorphism. 19 Acetylenic DOC is an inhibitor which preferentially inhibits the 19-hydroxylation of DOC, and does not interfere with the 18- and 11 beta-hydroxylation. This inhibition leads to a reduction in blood pressure in the S/JR Dahl rat. We suggest that an S/JR 19-nor-DOC is involved in the development of salt sensitivity and hypertension and that inhibition of its formation by acetylenic DOC and other aromatase and non-aromatase inhibitors is associated with reversal of these phenomena. PMID- 8481339 TI - Factors controlling steroid biosynthesis in the zona glomerulosa of the adrenal. AB - The biosynthesis of aldosterone in the adrenal zona glomerulosa is influenced by a number of factors of which the main physiological regulator is the octapeptide, angiotensin II (AII). Sodium restriction increases plasma aldosterone, adrenal glomerulosa AII receptors and the activity of enzymes of the early and late aldosterone biosynthetic pathway. The effects of sodium restriction are mimicked by prolonged administration of low doses of AII, and prevented by blockade of AII formation using converting enzyme inhibitors, indicating that the effects of sodium restriction are mediated by AII. However, the adrenal glomerulotrophic actions of AII are impaired in rats on high sodium diet indicating that other factors are modulating the effects of AII in these conditions. A number of factors are known to influence aldosterone secretion, several of which have been shown to preferentially modulate the effect of AII. While the stimulatory effect of AII is potentiated by serotonin or increases in extracellular potassium, it is inhibited by dopamine, somatostatin and atrial natriuretic peptide. Future investigations will be important to understand the relative role of the individual regulators in the physiological control of adrenal sensitivity to AII, and how activation of various intracellular messenger systems results in changes in activity of the enzymes of the aldosterone biosynthetic pathway. PMID- 8481340 TI - Final steps of aldosterone biosynthesis: molecular solution of a physiological problem. AB - The final two steps of aldosterone biosynthesis play a key role in the complex physiological adaptation of aldosterone secretion to changes in sodium and potassium content of the mammalian organism. The nature and identity of the enzyme catalyzing these steps have only recently been established. In the rat as well as in the human adrenal, two types of cytochrome P-450(11 beta) are encoded by two different genes. The major type of the enzyme catalyzes only the conversion of deoxycorticosterone to corticosterone or 18-hydroxy-11 deoxycorticosterone; it is present in all the zones of the adrenal cortex. The second type of the enzyme catalyzes the three steps involved in the conversion of deoxycorticosterone to aldosterone and occurs only in the zona glomerulosa. In rat zona glomerulosa cells, separate control systems independently regulate the expression of the two genes, according to long-term in vivo experiments or to experiments with primary cultures of zona glomerulosa cells. Expression of the non-aldosterone-producing enzyme is induced by ACTH, whereas the expression of the aldosterone-producing enzyme is dependent on the extracellular potassium concentration. PMID- 8481341 TI - The forms and functions of 11 beta-hydroxysteroid dehydrogenase. AB - In this review, we consider the relationship between the structure and function of 11 beta-hydroxysteroid dehydrogenase (11-HSD) purified from rat liver. The rat liver enzyme is a single domain glycoprotein with a unique active site and belongs to the short chain alcohol dehydrogenase family. Evidence supporting the presence in other tissues of 11-HSD isoforms is discussed. PMID- 8481342 TI - Role of androgens in breast cancer. AB - There is a vast amount of information on the concentration of different androgens in human breast cancer in pre- and post-menopausal women. Many years ago it was suggested that some androgens, in particular dehydroepiandrosterone (DHA), could be one of the parameters to establish whether these androgens can predict breast cancer. However, the enormous data available on the plasma and tissue concentrations, particularly DHA and DHA sulfate (DHA-S) allow confirmation that the quantitative values of these androgens are not significantly different in normal women from those with breast cancer. Another important aspect of androgens in breast cancer is their function as precursors of estrogens, hormones which play an important role in breast cancerization. However, it is not clear at present what the quantitative contribution of androgens "via aromatase" is to the formation of estrogens, because more recently it was found that estradiol in breast cancer tissues originates mainly "via sulfatase" using estrone sulfate as precursor. A point of further interest is that a series of authors have demonstrated that the administration of DHA to experimental animals with breast cancer significantly decreased the evolution of the disease. This part of the data is also contradictory because other experimental information has shown that administration of DHA can increase the incidence of granulosa cell tumors. Finally, it has been suggested that androgens, in their capacity as anti estrogens, can be used to substitute anti-estrogens in cases where treatment with classical anti-estrogens has no response. In conclusion, more information concerning the plasma and tissular concentrations of androgens, their contribution as estrogen precursors and their biological response(s), is needed in order to have a clearer idea of the role of these steroids in breast cancer. PMID- 8481343 TI - The pathology of Cushing's disease. AB - In this brief review the pathology of Cushing's disease is summarized. The most frequent morphologic abnormality is a basophilic microadenoma of the pituitary accompanied by the Crooke's hyaline change in the cytoplasm of nontumorous corticotrophs. Other tumor variants include chromophobic macroadenomas, Crooke's cell adenomas and corticotroph carcinomas. In some cases, no tumor can be documented in the pituitary. In the adenohypophyses of a few patients with hypercorticism, corticotroph hyperplasia is present which may be the cause of Cushing's disease. The pathogenesis of Cushing's disease is not clear. The question of whether corticotropin-releasing hormone (CRH) plays a role in its genesis has yet to be elucidated. Studies on animals and observations on human pituitaries indicate that CRH can induce accumulation of corticotrophs. Although no evidence is available to prove that CRH is involved in the neoplastic transformation of corticotrophs, it is possible that hypothalamic peptides which stimulate ACTH secretion may play a role in the progression of corticotroph adenoma of the pituitary. PMID- 8481344 TI - The structure of glucocorticoid receptors. AB - The glucocorticoid receptor of mouse thymic lymphoma cells was investigated. The receptor-hormone complex in cytosolic extracts has a Stokes' radius of 82 A and Mw approximately 330 kDa. In the presence of salt at high concentrations, however, the receptor-complex has a Stokes' radius of 60 A and Mw approximately 120 kDa. This receptor form is able to interact with DNA. Chemical cross-linking was used to stabilize the high molecular weight receptor structure against subunit dissociation and this was found to prevent receptor activation to DNA binding. The affinity labeled receptor was submitted to progressive cross-linking and the intermediate cross-linked forms were analyzed. This led to the conclusion that the high molecular weight receptor structure is a hetero-tetramer consisting of one receptor polypeptide of approximately 100 kDa, two molecules of the 90 kDa heat shock protein hsp90 and an additional protein subunit. The latter was unequivocally identified by immunochemical techniques as the 59 kDa protein p59. The 70 kDa heat shock protein was found not to be a bona fide receptor component but was a contaminant of our immunopurification procedure. Cross-linking studies also showed that the receptor exists in the high molecular weight form in intact cells and in the absence of hormone. PMID- 8481345 TI - Reduced aldosterone metabolites in hypertension. AB - Significant quantities of 5 alpha and 5 beta-Ring A-reduced metabolites and several polar cytochrome P-450 dependent hydroxylated neutral metabolites of aldosterone (Aldo) (NMA) are soon present in the kidney during the latent period, prior to the expression of Aldo's effects on Na+ and K+. Their levels in the kidney (a) correlate, in a dose-dependent manner, with the magnitude of physiological responses to Aldo in male rats, (b) are lower in the kidneys of females, which show smaller responses to Aldo than males, (c) are lower in the kidneys of males treated with the anti-mineralocorticoid spironolactone, and (d) their synthesis can be regulated by dietary Na+ and K+. Anti-mineralocorticoids completely inhibit synthesis of 5 alpha-reduced metabolites of Aldo in both kidney and toad bladder and of several of the polar hydroxylated NMA in both liver and kidney. 5 alpha-Reduced metabolites and their 2-hydroxylated derivatives possess significant mineralocorticoid activity and their synthesis is increased in rats fed a low Na+ diet and decreased with a high Na+ diet. We have suggested that their synthesis may play a major role in the expression and/or regulation of the individual renal anti-natriuretic and kaliuretic actions of Aldo. PMID- 8481346 TI - Corticosteroid receptors and aging. AB - We have measured plasma aldosterone, plasma cortisol, and glucocorticoid and mineralocorticoid receptors in mononuclear leukocytes in 54 healthy aged subjects (60-97 years old) and in a group of 21 controls (21-50 years old). In addition all parameters and age were plotted for correlation. Plasma cortisol was significantly higher in the aged group (346 +/- 140 nmol/l) than in controls (260 +/- 120). Mean plasma aldosterone was not different in the two groups. Both Type I and II receptors in mononuclear leukocytes were lower in the aged group than in controls (Type I 198 +/- 96 and 272 +/- 97 receptors per cell; Type II 1738 +/- 801 and 3339 +/- 918 receptors per cell). A direct correlation was found between cortisol and age and between Type I and II receptors in aged subjects, and between cortisol and Type I receptors, and cortisol and Type II receptors in controls. When all subjects are plotted together, a direct correlation was observed between cortisol and age and between Type I and II receptors, and an inverse correlation between age and Type I and age and Type II receptors. We conclude that the parallel reduction of both Type I and II receptors with age is not due to prior cortisol increase, but the increase of plasma cortisol can be considered the result of age-dependent involution of these receptors. PMID- 8481347 TI - The role of vascular steroid receptors in the control of vascular contractility and peripheral vascular resistance. AB - Evidence is presented that glucocorticoids (GC) and mineralocorticoids (MC) control contractility of vascular smooth muscle (VSM). This control is effected through the in situ mechanism for the action of these steroids in the arterial and arteriolar wall. This action is mediated through GC and MC receptors in the VSM cell. Acting through these receptors, MC and GC increase transport capacities of different transmembrane transport systems for Na+ and/or Ca2+ through induction of synthesis of proteins constituting the transport systems. Colocalization of enzymes deactivating cortisol in VSM, with VSM receptors for GC and MC further strengthens the concept that the arterial network houses an in situ molecular mechanism for the control of VSM contractility, thus peripheral vascular resistance. PMID- 8481348 TI - Paracrine regulation of the renin-aldosterone system. AB - A number of clinical states have been described where there are derangements or discrepancies between renin-angiotensin and aldosterone secretion. We have studied the potential effect of some cytokines or growth factors (peptide regulatory factors) on this system in vitro. Both tumor necrosis factor/cachectin and interleukin I are potent regulators acting as renin secretagogues and inhibitors of aldosterone synthesis. These actions are mediated by prostaglandin cyclooxygenase products and their actions mimic the syndrome of hyperreninemic hypoaldosteronism in critical illness. Insulin and insulin-like growth factor I are also renin secretagogues in vitro However in a diabetic model (streptozotocin rat), there is resistance to both agonists as well as enhanced feedback suppression to angiotensin. A third peptide, transforming growth factor (TGF beta) has even more complex actions, acting as a secretagogue at low doses (10( 12) M) but inhibiting renin at higher doses. TGF beta production is increased in the diabetic state so that this peptide as well as the insulin family may be involved in hyporeninemic hypoaldosteronism. PMID- 8481349 TI - Angiotensin II and dexamethasone regulate angiotensinogen mRNA by different mechanisms. AB - Angiotensinogen synthesis and secretion in the liver is regulated by glucocorticoids and angiotensin II. In isolated hepatocytes in suspension culture, both dexamethasone and angiotensin II induced an increase in angiotensinogen mRNA (2.5- and 4-fold, respectively) with half maximal stimulation at 20 and 200 nM, respectively. In a nuclear run on assay, transcription of the angiotensinogen gene in nuclei from hepatocytes exposed to angiotensin II was not significantly different from controls, whereas dexamethasone-pretreatment dramatically stimulated angiotensinogen mRNA synthesis. By inhibition of transcription in hepatocytes, as well as in [32P]uridine pulse and chase experiments, angiotensin II was shown to stabilize angiotensinogen mRNA, prolonging the intracellular half-life from 83 to 191 min. In polysomal extracts from hepatocytes, a 12 kDa protein could be identified, that binds to a probe of the 3'-untranslated region (UTR) angiotensinogen mRNA. The binding activity of this protein appears to be higher in hepatocytes exposed to angiotensin II, and to have a stabilizing effect on angiotensinogen mRNA. It is proposed that angiotensin II enhances the binding activity of a 12 kDa protein the 3'-UTR of angiotensinogen mRNA, which results in increased stability and transcription of angiotensinogen mRNA. PMID- 8481350 TI - Changes in the renin-angiotensin system after nephrectomy and adrenalectomy. AB - The study investigates the change in angiotensinogen (Aogen), angiotensin I (AngI) and renin plasma concentration after nephrectomy and adrenalectomy. The aim of the study was to elucidate the mechanisms that are involved in the up regulation of the Aogen plasma levels after nephrectomy and the contribution of the adrenals. Rats were treated with the beta 1-selective adrenoceptor blocker, atenolol, and with the angiotensin antagonist, DuP 753 in order to inhibit renal renin release and to check whether the increase in plasma Aogen after nephrectomy is mediated by angiotensin (AngII), respectively. The plasma Aogen levels increase approx. 5-fold 24 h after nephrectomy. This increase is significantly reduced in the presence of atenolol. After nephrectomy plus adrenalectomy there is a maximal increase of 60% in plasma Aogen levels 8 h after surgery and a subsequent decline. In the presence of atenolol this increase is even smaller. In contrast after adrenalectomy the plasma Aogen levels continuously declined. In the presence of atenolol the plasma Aogen levels were approx. 20% higher at time 0 but declined with the same slope as after adrenalectomy without atenolol treatment. Treatment with DuP 753 caused an almost complete inhibition of the increase in Aogen plasma levels after nephrectomy. Significantly higher Aogen levels were found only after 24 h. At time 0, immediately after nephrectomy the plasma AngI levels were increased compared to the respective control rats. Significantly higher AngI values (P < 0.05) could also be observed in nephrectomized rats and in nephrectomized plus adrenalectomized rats at time 0 in the presence and absence of atenolol and DuP 753, respectively. In contrast after adrenalectomy alone the AngI levels at time 0, were not different from those of the controls. Subsequently the AngI levels increased at a similar rate as after adrenalectomy in the presence of atenolol. These findings suggest that the increase in plasma Aogen after nephrectomy is essentially mediated by AngII via an adrenal mechanism. It seems likely that this process is triggered by renin released during surgery. The increased renin release after adrenalectomy that is responsible for the increased degradation of Aogen seems not to be mediated by a sympathetic stimulation of the renal beta 1-adrenoceptors. PMID- 8481351 TI - Differential diagnosis in primary aldosteronism. AB - The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists of a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with PA are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51 and 44%, respectively. They had similar blood pressure levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma also had higher values of the aldosterone precursor 18 hydroxy-corticosterone, and of atrial natriuretic peptide, probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radiocholesterol scintiscan provided similar results (85% accuracy): adrenal veins catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dexamethasone-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldosterone, 18-hydroxy-corticosterone, 18-hydroxy-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system. Isolated cases of primary adrenal hyperplasia (with all functional tests resulting compatible with APA, but no tumour at surgery) and aldosterone producing carcinoma (1 case) have also been reported in the present study. PMID- 8481352 TI - Mineralocorticoid production of adrenal cortical adenomas. AB - We studied in vitro and in vivo corticosteroid production as well as the presence of symptoms of an increased mineralocorticoid effect in patients with 'silent' adrenal cortical adenomas, and compared these results to those found in patients with classical mineralocorticoid excess syndromes. We found that under in vitro conditions, cells from 'silent' adrenal cortical adenomas (n = 19) produced substantial amounts of both zona glomerulosa and fasciculata steroids, although the production of steroids in these cells was lower compared to that in mineralocorticoid-producing adenoma cells (n = 26). Patients with aldosterone producing and 'silent' adenomas had significantly increased plasma atrial natriuretic peptide levels, which remained non-suppressible after upright posture and furosemide administration. Of the 25 patients with 'silent' adenomas, 11 had low and non-stimulable plasma renin activity (PRA) before but, in most cases, not after adrenal surgery. When compared to those with normal PRA (n = 14), patients with low PRA 'silent' adenomas (n = 11) had higher blood pressure which was significantly reduced after surgery, and a mild hypokalemia before but not after surgery. Although basal plasma concentrations of aldosterone, 18-hydroxy corticosterone, corticosterone, deoxycorticosterone, 18-hydroxy-DOC, cortisol,11 deoxycortisol and 17-hydroxy-progesterone (17-OH-P) were not increased in either groups of 'silent' adenomas, ACTH stimulation produced a hyperreactive response for all measured steroids, of which an extremely high 17-OH-P seemed to be one of the most intriguing findings. We consider that these observations in 'silent' adrenal cortical adenomas may justify surgical intervention, irrespective of the size and potential malignancy of these adenomas. PMID- 8481353 TI - Problems in diagnosis and management of congenital adrenal hyperplasia due to 21 hydroxylase deficiency. AB - A number of biochemical tests have been utilized to assist the diagnosis of steroid 21-hydroxylase deficiency. The specificity and accuracy of plasma 17 hydroxyprogesterone assays are important. A profile of steroids in urine by gas chromatography and mass spectrometry is the definitive test. Molecular biology is not practical for the diagnosis of a new case. The ACTH stimulation test for detection of heterozygotes is a poor discriminant. Fertility in patients with congenital adrenal hyperplasia may be due to excess of progesterone as well as of androgens. Gene amplification offers the best approach in molecular biology for the prenatal diagnosis of 21-hydroxylase deficiency. PMID- 8481354 TI - Prenatal diagnosis and treatment of 21-hydroxylase deficiency. AB - Prenatal diagnosis of 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia (CAH), has benefited from the advances in endocrinologic and molecular genetic studies. In 1976, prenatal diagnosis of the disease was first attempted by measuring 17-hydroxyprogesterone in the amniotic fluid in the second trimester of pregnancy. Discovery of a close linkage between HLA and the disease gave a second approach for prenatal diagnosis, the latter being made by linkage study of the haplotypes of the index case in a given family. Diagnosis was later made directly by molecular biology. Currently, the studies of the C4-CYP21B gene locus by Southern blotting and the CYP21B gene mutations by PCR methods simplify the diagnostic procedure of an early and accurate prenatal diagnosis in the first trimester. In these conditions all families are now informative. Moreover, using a direct genetic analysis associated with the possibility of detecting the heterozygotes in a non-related CAH population, a prenatal diagnosis can be done in a family without a previously CAH affected child. From our results in a series of 274 pregnancies at risk for CAH in whom prenatal diagnosis has been made by these different approaches, it can be concluded that steroid analysis in the amniotic fluid is an accurate method but provides only a late (second trimester) diagnosis, while an early and accurate diagnosis now relies on adequate molecular genetic studies on chorion villus biopsies. In the aim to prevent the virilization of the external genitalia in CAH female fetuses, prenatal treatment was instituted in our group in 1979 by giving dexamethasone to the mother. This prenatal treatment appears safe for the fetus and the child and is effective in preventing virilization of CAH affected females. Although the degree of prevention is not always complete in all cases, the advantages of prenatal treatment are prevailing over the complications observed in a few mothers. PMID- 8481355 TI - Male pseudohermaphroditism caused by nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency. AB - We observed a boy with ambiguous genitalia and normal testes. Steroid analyses performed during newborn age surprisingly were inconclusive basally and after hCG stimulation, but showed an insufficient testosterone response. Possibly during the early postnatal period the 3 beta-HSD activity in peripheral tissues may have been sufficient to substitute for the deficient 3 beta-HSD activity in the adrenal and gonads. In contrast at 11 and 22 months basal as well as ACTH stimulated levels of 17OHPreg, DHEA and testosterone were typical for a 3 beta HSD defect. PMID- 8481356 TI - Congenital lipoid adrenal hyperplasia--genes for P450scc, side chain cleavage enzyme, are normal. AB - In the most severe form of congenital adrenal hyperplasia (CAH), termed lipoid CAH, both the adrenals and gonads fail to convert cholesterol to pregnenolone, so that no steroid hormones are made. Newborns have female external genitalia irrespective of karyotype, and suffer a severe salt-losing form of CAH. Previous studies have shown that adrenal or gonadal mitochondria from these patients also fail to convert cholesterol to pregnenolone in vitro, implicating a lesion in the single gene for P450scc, which is the sole enzyme converting cholesterol to pregnenolone. Two patients with XY karyotypes had female genitalia and unmeasurable steroids after stimulation with ACTH and hCG. ACTH stimulation tests of parents, obligate heterozygotes, showed normal stimulation of all precursor steroids. Southern blotting patterns of the P450scc gene were normal. Oligonucleotide-initiated enzymatic amplification (PCR) of all P450scc exons showed normal sequences on multiple amplifications and sequencing reactions, indicating normal P450scc genes. Northern blots of testicular RNA from a 6-month old patient and from a control fetus showed normal P450scc mRNA, indicating a normal P450scc promoter. Reprobing of the blot with our cloned human cDNAs for adrenodoxin reductase and adrenodoxin showed that these electron transport cofactors used by P450scc were also normal. Similarly, probing with cDNAs for all three known factors involved in cholesterol transport to the mitochondria-sterol carrier protein 2, endozepine, and steroidogenesis activator peptide were also normal. These results suggest that the lesion in lipoid CAH is not in the P450scc system or in any known step upstream from P450scc. PMID- 8481357 TI - Mutations in human 11 beta-hydroxylase genes: 11 beta-hydroxylase deficiency in Jews of Morocco and corticosterone methyl-oxidase II deficiency in Jews of Iran. AB - Steroid 11 beta-hydroxylase is encoded by two homologous genes, CYP11B1 and CYP11B2, located on chromosome 8q21-22. CYP11B1 encodes a specific cytochrome P 450 (P-450c11) necessary for cortisol biosynthesis, with predominantly 11 beta hydroxylase and moderate 18-hydroxylase activity, whereas CYP11B2 encodes another isozyme (P-450cmo) necessary for aldosterone biosynthesis, with 11 beta hydroxylase, 18-hydroxylase and 18-oxidase activities (the latter two termed corticosterone methyl-oxidase I and II; CMO-I and II, respectively). Two steroid biosynthetic defects, both relatively frequent in Israel, are caused by specific mutations in each of these genes. 11 beta-Hydroxylase deficiency is frequent among Jews from Morocco (1 in 5000 to 7000 births), and is characterized by virilization, hypertension, impaired cortisol biosynthesis, and increased deoxycorticosterone and androgens. Affected individuals have a single base substitution in exon 8 of CYP11B1, codon 448, from CGC (arginine) to CAC (histidine). This sequence, normally absent in CYP11B2, constitutes a true point mutation within the heme binding domain of CYP11B1 that results in marked impairment of enzymatic activity. The clinical expression is characterized by a wide range of variability in the signs of both androgen and mineralocorticoid excess, even though an identical mutation was found in all but one of the affected alleles examined. CMO-II deficiency is frequent among Jews from Iran (1 in 4000 births), and is characterized by a typical salt-wasting syndrome, increased 18-hydroxycorticosterone, impaired aldosterone biosynthesis, and a high ratio of these steroids. No mutation was found in CYP11B1, but all individuals affected were homozygous for two missense mutations in CYP11B2. The first, in exon 3, codon 181, from CGG (arginine) to TGG (tryptophane) is a mutation that completely abolishes both CMO-I and II activities, whereas the second, in exon 7, codon 386, from GTG (valine) to GCG (alanine) is a more conservative substitution that produces only a minimal reduction in CMO-I activity. Individuals homozygous for either one of these mutations are asymptomatic. PMID- 8481358 TI - Stage I endometrial carcinoma: the role of neoadjuvant progesterone therapy. AB - A prospective study was devised in 1980 to assess the effect on survival of neoadjuvant Provera as part of the primary treatment of endometrial carcinoma in conjunction with surgery and radiotherapy. Between June 1980 and June 1985, 218 patients with Stage I adenocarcinoma of the corpus uteri were allocated on the basis of hospital of presentation to receive either neoadjuvant treatment with medroxyprogesterone acetate (MPA) 100 mg t.i.d. p.o. from diagnosis for 90 days, or no adjuvant treatment (the control group). The minimum follow-up was 5 years. There was no significant difference between the overall actuarial survival in the treatment group (123 cases) and that in the control group (95 cases). This was 83.7% and 69.2% at 5 and 10 years respectively in the treatment group and 78.9% and 70.7% in the control group (P > 0.1). PMID- 8481359 TI - Sustained indomethacin and ranitidine with intermittent continuous infusion interleukin-2 in advanced malignant melanoma: a phase II study. AB - Experimental work has shown that, during the development of tumours, host macrophages are triggered to produce high levels of prostaglandin E2 which inactivates natural killer cells and suppresses lymphokine activated killer cell development. Sustained, uninterrupted indomethacin treatment, when combined with interleukin-2 (IL-2), can totally eradicate experimental metastases. Most trials utilizing high dose IL-2 employ indomethacin and ranitidine in order to alleviate or prevent IL-2 toxicity, but only administer these medications concurrently with IL-2 therapy. A Phase II trial was conducted in patients with advanced melanoma. Patients received 50-75 mg indomethacin three times daily and 150 mg ranitidine twice daily, starting at least 1 week prior to IL-2 and continuing until intolerance or disease progression. Continuous venous infusion IL-2 was administered for three courses, each consisting of 5 days of treatment at 18 x 10(6) iu/m2/day for the first course with escalation of dose for the subsequent courses if toxicity allowed. Twenty-one patients were eligible to receive all components of therapy. Three patients achieved an objective response (one complete and two partial), giving a response rate of 14%. However, two of these objective responses (one complete and one partial) were achieved on indomethacin and ranitidine alone, prior to the commencement of IL-2 therapy. In this study, indomethacin and ranitidine, without IL-2, have been shown to have antitumour activity in advanced melanoma; continuous infusion IL-2 appeared to add little to the response seen with these two agents. PMID- 8481360 TI - Isolated cutaneous relapse in Hodgkin's disease: a case report and review of the literature. AB - Cutaneous Hodgkin's disease is uncommon, and is usually associated with evidence of systemic disease. We report a case of apparently isolated cutaneous relapse in a patient with Hodgkin's disease, and review the literature on cutaneous Hodgkin's disease as a whole. PMID- 8481361 TI - Non-Hodgkin's lymphoma presenting with jaundice and hypercalcaemia. AB - A patient is reported with B-cell lymphoma (centroblastic high grade non Hodgkin's) with pancreatic involvement, who presented with jaundice and hypercalcaemia. Particularly unusual features include the presentation with a pancreatic mass and the association of hypercalcaemia with centroblastic lymphoma. PMID- 8481362 TI - The successful use of radiotherapy for osteoblastoma. AB - We report a case of osteoblastoma arising in the petrous temporal bone of a 16 year-old boy. Attempts at surgical resection were unsuccessful. The patient was treated with radiotherapy and is now well 10 years later. A review of the literature indicates that radiotherapy has been used rarely for this tumour and some have felt it to be detrimental. Our report illustrates a case where planned radiotherapy has been successful when full surgical resection had not been possible. PMID- 8481363 TI - Assessment of visual function for patients on tamoxifen. PMID- 8481364 TI - Radiotherapy patient scheduling. PMID- 8481365 TI - A comparison of doxorubicin, epirubicin and mitozantrone as single agents in advanced breast carcinoma. AB - Between July 1985 and December 1987, 87 patients with advanced breast carcinoma were randomized to receive single agent doxorubicin (70 mg/m2), epirubicin (70 mg/m2) or mitozantrone (14 mg/m2) at 3-weekly intervals. The patients had received no previous chemotherapy for their advanced disease but 91% had received prior hormonal therapy. The response rates were 36% with doxorubicin, 32% with epirubicin and 26% with mitozantrone, but these differences did not reach statistical significance. The median survival of all patients was 8.3 months. There was no significant difference in response rates or survival according to menopausal status. The toxicities of the three agents are compared. Nausea, vomiting and alopecia were more severe in patients treated with doxorubicin or epirubicin than those treated with mitozantrone. Myelosuppression and infective episodes occurred more frequently with mitozantrone. Two cardiac complications were reported. This study shows that the toxicity and low efficacy of all three agents limit their use as single agents in advanced breast carcinoma. The role of single agent chemotherapy and the relative toxicities of these drugs are discussed. PMID- 8481366 TI - Women and clinical oncology. AB - In the United Kingdom 20% of consultants and 23% of senior registrars are female. A questionnaire sent to female clinical oncologists revealed that 90% have full time contracts, although 36% had spent time in part-time training. Sixty-seven per cent of the total have children and the husbands of 51% of the 74% who are married are doctors. Twenty-four per cent believe they have experienced sexual discrimination in clinical oncology and 10% believe they have failed to be appointed to a post because of their gender. Problems highlighted were of inadequate funding for locums to cover maternity leave and poor child care facilities. PMID- 8481367 TI - Radiotherapy patient scheduling using a desktop personal computer. AB - This paper describes the transition from a conventional paper based patient scheduling system for radiotherapy to a computer based system in a busy clinical department. The hardware and software requirements are set out, together with a description of the current advantages and future potential for development of the system as part of a mathematical model of departmental activity. PMID- 8481368 TI - Myopic keratomileusis with the excimer laser: one-year follow up. AB - BACKGROUND: The possibility of using an argon fluoride excimer laser to perform the refractive incision in keratomileusis spurred us to develop the present surgical technique of using a microkeratome to make a primary corneal incision that yields a corneal disc, then making the refractive excision of stroma with excimer laser ablation, and finally suturing the corneal disc in place. METHODS: We describe the procedures and a prospective study of 30 consecutive eyes from 22 consecutive patients with high myopia (range, -11.20 D to -24.50 D) who underwent excimer laser myopic keratomileusis. A plano corneal disc was cut with a BKS 1000 microkeratome, followed by argon fluoride excimer laser ablation of the stroma with the Summit Eximed UV 200LA laser (Summit Technology, Inc, Waltham, Mass), either of the resected disc (28 eyes) or in situ on the stromal bed (two eyes). RESULTS: By 3 weeks after surgery, 83% of the corneas were considered clear. In 17 eyes (57%), the difference between the intended and achieved refraction was < 1.00 D; in 9 eyes (30%), the difference was 1.00 to 3.00 D; in 4 eyes (13%), the difference was 3.00 to 6.00 D. At 12 months after surgery, uncorrected visual acuity was 20/40 or better in 3 (10%) eyes, and 20/50 to 20/100 in the remaining 27 (90%) eyes, in contrast to 100% of eyes that saw worse than 20/200 before surgery. Two eyes had a very deep ablation of the lenticule that led to irregularities in Bowman's layer. CONCLUSIONS: Excimer laser myopic keratomileusis is an effective way to correct high myopia and may be more accurate than other methods of keratomileusis. A new nomogram for the procedure is presented. PMID- 8481369 TI - Excimer laser photorefractive keratectomy for hyperopia. AB - BACKGROUND: Excimer laser photorefractive keratectomy has generated considerable interest as a technique for correcting myopia. In this study, the excimer laser was used to correct hyperopia. METHODS: A prospective clinical study based on the results of photorefractive keratectomy in 23 consecutive hyperopic eyes (one eye per patient) is presented. The excimer laser used in this study was a MEL 60 (Aesculap-Meditec); this laser emits 193-nanometer laser light. A 1-year follow up study of two groups of eyes was performed. All patients were followed for 12 months. The first group comprised 15 hyperopic eyes with preoperative refraction between +2.0 and +7.5 diopters (mean spherical equivalent +4.7 +/- 1.6 D). The second group comprised eight aphakic eyes with preoperative refraction between +11.0 and +16.0 D (mean spherical equivalent +13.1 +/- 2.0 D). RESULTS: In group 1, 12 eyes (80%) were within +/- 1.0 D of the intended correction (baseline, +2.0 to +7.5 D) after 1 year. In group II, only three of the eight aphakic eyes (37%) were within +/- 1.0 D of the intended final refraction (baseline, +11.0 to +16.0 D). The stability of refraction in group I was better than in group II. At 12 months, best corrected visual acuity was unchanged in 14 eyes of group I. One eye had lost two lines. In group II, best corrected visual acuity was unchanged in six eyes after 12 months. In two eyes, best spectacle-corrected visual acuity was lower than the preoperative value, because of decentration of the ablation zone. After 1 year, 80% of the eyes in group I and 25% of those in group II had a visual acuity of 20/40 or better. CONCLUSION: Photorefractive keratectomy is an efficient and relatively safe procedure for correcting hyperopia up to +7.5 D. The predictability is good. Results of photorefractive keratectomy to correct highly hyperopic (aphakic) eyes are not as encouraging. Three patients in this study lost one to three lines of best spectacle-corrected visual acuity due to decentration of the clear zone. Two of the patients belonged to group II. Therefore, we do not recommend photorefractive keratectomy in highly hyperopic eyes, especially if they are aphakic, because even slight decentration may lead to loss of best corrected visual acuity. As in other refractive surgical procedures, great care must be taken to improve the centration of the clear zone. PMID- 8481370 TI - Long-term endothelial cell loss following phacoemulsification: model for evaluating endothelial damage after intraocular surgery. AB - BACKGROUND: Newer concepts of phakic intraocular lens (IOL) surgery present concerns as to their long-term deleterious effect on the endothelium. We examine the behavior of the endothelium for up to 6 years following uneventful phacoemulsification surgery, to establish a baseline for what might be an acceptable level of endothelial cell loss due to intraocular surgical trauma. METHODS: Ninety-three eyes undergoing phacoemulsification surgery who had multiple endothelial specular microscopy examinations for up to 6 years were examined. Central endothelial specular photomicrographs were analyzed in all cases and the percent of endothelial cell loss as a function of time was calculated. Cell density calculations were corrected for the normal endothelial cell loss as a function of age. RESULTS: Routine uncomplicated phacoemulsification surgery demonstrated a 9% endothelial cell loss 1 year postoperatively. This is in marked contrast to the 16% average endothelial cell loss cited in the literature after phakic AC-IOL surgery. In general, anterior chamber IOL surgery following cataract removal compares unfavorably to posterior chamber IOL insertion long term (20% cell loss versus 12% cell loss). CONCLUSIONS: A model is proposed to look at the rate of endothelial cell loss that would be significant enough to create the threat for corneal edema long term following refractive intraocular surgery in young patients. Suggestions for critical comparisons between the observed endothelial aging seen with phakic IOLs and values for more routine IOL surgery are proposed to predict the long-term threat for endothelial cell loss and corneal decompensation, which might result many years after phakic refractive IOL surgery. PMID- 8481371 TI - Comparison of excimer laser and microkeratome myopic keratomileusis in human cadaver eyes. AB - BACKGROUND: There are currently four techniques of keratomileusis in clinical use: cryolathe, planar with mold, excimer laser, and in situ. Comparative studies among the techniques are rare in human cadaver eyes. We studied the newest of these techniques using the argon fluoride (193 nm) excimer laser to perform the excision of stroma as compared to the nonfreeze, planar, lamellar myopic keratomileusis using the Barraquer-Krumeich-Swinger (BKS) technique. METHODS: Corneas were dehydrated in dextran-containing medium. A 9.00-diopter correction was attempted with each technique using the manufacturers' parameters. There were six eyes in each group. Keratometry was done with the instrument (Bausch & Lomb) mounted vertically. RESULTS: The laser group achieved a mean keratometric flattening of 5.80 +/- 1.00 D; the BKS group achieved a flattening of 3.80 +/- 1.30 D. CONCLUSIONS: These results demonstrated the difficulty in obtaining results in eye-bank eyes that match those achieved clinically. The different results of these two techniques underscore the need to use clinical data to adjust laser keratomileusis operating parameters. PMID- 8481372 TI - Optics of the corneal epithelium. AB - BACKGROUND: The refractive effect of the corneal epithelium in relation to the cornea as a whole is relatively unknown, yet it may affect the efficacy of keratorefractive surgical procedures, most notably photorefractive keratectomy and epikeratoplasty. This article investigates the refractive effect of the epithelium on the cornea. METHODS: We measured the corneal keratometry in 10 fresh human eye-bank eyes with and without epithelium. All readings were performed at 2.0- and 3.6-millimeter diameter zones with an automated keratometer. RESULTS: When the epithelium was removed, there was an increase in corneal refractive power in every case. The mean change was +1.03 D (range, 0.55 to 1.85 D) at the central 2.0-millimeter diameter zone and +0.85 D (range, 0.29 to 1.60 D) at the 3.6-millimeter diameter zone. We also found a change in both the power and axis of astigmatism in most cases. CONCLUSIONS: The corneal epithelium plays an active role in determining the final surface power of the cornea. It accounts for an average of 1.03 D of the power of the eye at the central 2-millimeter diameter zone. The difference in astigmatism suggests that the epithelium does not form a layer of uniform thickness over Bowman's layer. It appears that the epithelium attempts to minimize abrupt changes in surface contour. These findings suggest that in refractive procedures such as photorefractive keratectomy the refractive contribution of the epithelium must be taken into account to improve predictability. PMID- 8481373 TI - Four-incision radial keratotomy for high myopia after penetrating keratoplasty. AB - BACKGROUND: High amounts of myopia can frequently produce anisometropia and limit visual rehabilitation by conventional means in eyes with clear corneal grafts. This condition is frequently coupled with large amounts of astigmatism. Four incision radial keratotomy provides a way to reduce myopia in normal individuals. In our present study, we used the technique of four- incision radial keratotomy to reduce myopia in a group of keratoplasty patients who failed conventional visual rehabilitation. Arcuate or transverse keratotomy was used in conjunction with radial keratotomy in eyes with high amounts of astigmatism. METHODS: This study retrospectively examined a group of 11 eyes with penetrating keratoplasty which underwent four-incision radial keratotomy for the treatment of visually disabling myopia. The radial incisions were placed in the graft, inside the graft host interface. Seven eyes underwent concomitant arcuate relaxing incisions at the graft-host interface for treatment of associated astigmatism. One additional eye had paired straight transverse incisions for the treatment of astigmatism. The mean postoperative follow up was 16 months (range, 3 months to 5 years). RESULTS: There was a mean reduction of the spherical equivalent refraction of 3.48 diopters (D) (range, 0.25 to 7.75 D). The eight eyes undergoing astigmatic surgery showed a mean reduction in keratometric astigmatism of 2.25 D (range, 6.75 to +6.50 D) and refractive astigmatism of 4.63 D (range, -1.50 to -9.50 D). Nine of the 11 eyes had stable or improved best spectacle corrected visual acuity. Two eyes had reduction of best spectacle corrected visual acuity--one due to development of irregular astigmatism and one due to worsening of preexisting macular edema. CONCLUSIONS: Four-incision radial keratotomy can reduce myopia after penetrating keratoplasty when the patient is unable to tolerate spectacle or contact lens correction. It can be combined with relaxing incisions or transverse keratotomy to reduce astigmatism. There is a high amount of variability, and predictability is currently limited by the complex topographical changes occurring in corneal transplants. Complex corneal biomechanical changes may predispose these eyes to the development of irregular astigmatism. PMID- 8481374 TI - Multifocal effect of against-the-rule myopic astigmatism in pseudophakic eyes. AB - BACKGROUND: In monofocal intraocular lens (IOL) implants we can sometimes obtain a certain degree of pseudoaccommodation. The use of a slight myopic astigmatism is proposed for postoperative refraction to achieve a significant increase in the depth of field and to reestablish a certain degree of pseudoaccommodation in pseudophakic eyes. METHODS: Eighty-one eyes with against-the-rule myopic astigmatism were evaluated in 50 patients who underwent IOL implant surgery. We selected patients with corrected monocular visual acuity greater than or equal to 20/30 and with a refraction ranging from +0.50 to -1.25 diopters sph, from -0.50 to -2.75 D cyl, ax from 55 degrees to 140 degrees. RESULTS: Monocular uncorrected distance visual acuity in 68% of eyes was 20/40 or better, while binocular uncorrected distance visual acuity in 84% of eyes was 20/40 or better and in 66% of eyes was 20/30 or better. Monocular uncorrected near visual acuity in 67% of eyes was J3 or better, while binocular uncorrected near visual acuity in 82% of eyes was J3 or better and in 68% was J2 or better. Sixty-four percent of patients never wear glasses for distance, while 34% use them occasionally and only 2% always wear them. Fifty-four percent of patients never wear glasses for near, 32% use them occasionally, while 14% always wear them. CONCLUSION: These data show that with a low against-the-rule simple myopic astigmatism (about -1.50 D cyl x 90) we can often offer pseudophakic patients a rewarding independence from glasses both for distant and near vision. PMID- 8481375 TI - The treatment of persistent wound leak after radial keratotomy. AB - BACKGROUND: Macroperforation of the cornea during refractive keratotomy can result in persistent wound leak and may need treatment by suturing. METHODS: We describe two eyes that developed a macroperforation during radial keratotomy with persistent leakage of aqueous. The wounds were sutured with 10-0 and 11-0 nylon sutures. RESULTS: The sutures induced irregular astigmatism as shown by corneal topography. Removal of sutures improved the topography and led to an acceptable outcome. CONCLUSION: Macroperforations with persistent aqueous leaks should be sutured. Suture removal within a few weeks after surgery can avoid persistent irregular astigmatism and lead to a good refractive result. PMID- 8481376 TI - Double Descemet's membrane in penetrating keratoplasty. AB - A rare complication of penetrating keratoplasty is incomplete removal of the host Descemet's membrane, which can progressively become opaque. Utilizing a Nd:YAG laser, we opened the opaque membrane, improving visual acuity from 20/400 to 20/100. PMID- 8481377 TI - Early rehabilitation after small incision cataract surgery. AB - BACKGROUND: The use of smaller cataract incision is thought to induce less astigmatism, resulting in a more stable refraction and more stable wound. METHODS: We have analyzed the early astigmatic changes and rehabilitation in 20 eyes of 16 patients operated with advanced phacoemulsification techniques. The patients operated with small-incision surgery (incision 4.0 mm) were compared to those with large-incision surgery (incision 7.5 mm). Keratometric values and visual acuity data were evaluated up to 6 months postoperatively. RESULTS: Less initial induced astigmatism was demonstrated at day 7 postoperatively with a 4.0 millimeter incision (0.1 +/- 0.53 D) compared with a 7.5-millimeter incision (1.90 +/- 1.97). Similar but not statistically significant changes were seen at days 1 and 30 postoperatively. Visual rehabilitation was also faster in the small incision group and 70% of the eyes gave uncorrected visual acuity of 20/40 or better in this group as early as the first postoperative day. Only 11% of the eyes showed that uncorrected visual acuity after large-incision surgery at first postoperative day. CONCLUSION: The low amount of induced cylinder, rapid stabilization of the wound, and faster visual rehabilitation confirms the advantage of small-incision cataract surgery to large-incision surgery. PMID- 8481378 TI - Achromobacter xylosoxidans keratitis following penetrating keratoplasty. AB - BACKGROUND: Achromobacter xylosoxidans is a bacterium not previously reported in a corneal infection. We present a case of infectious keratitis caused by this organism, occurring 1 month following penetrating keratoplasty. METHODS: Identification of the organism was accomplished by staining, culture, and sensitivity testing of the corneal scraping obtained from the involved area. The infection responded to subconjunctival ticarcillin, piperacillin eye drops, and I.V. azlocillin. RESULTS: Complete healing with a resultant corneal opacity involving mostly the anterior and middle stroma was achieved 1 month later. CONCLUSIONS: A. xylosoxidans should be considered as a potential pathogen in instances of early postkeratoplasty infectious keratitis. PMID- 8481379 TI - Isomorphic corneal topography: a clinical approach to 3-D representation of the corneal surface. AB - BACKGROUND: Newer methods of refractive surgery produce their effect by reshaping the corneal surface. It follows that topographic representations, used primarily to map refractive power, should now emphasize morphology and contour features. METHODS: We introduce a procedure using commercially available instrumentation which provides isomorphic three-dimensional corneal topography. The representations may be displayed either as refractive power, as is conventionally done, or as the more surgically relevant contour configuration. These images contain data points that are continuous rather than stepped as in the familiar color-coded displays. RESULTS: The technique proved easy to execute requiring no special software or mainframe computing. The corneal displays generated were freely rotatable and rescalable. CONCLUSIONS: In addition to producing clear and intuitive three-dimensional representations, the digital graphics environment allows manipulation unavailable in the conventional color-coded format; such representations should be particularly valuable for pre- and postoperative evaluation. PMID- 8481380 TI - In planning the number of incisions, size of the clear zone, etc, for radical keratotomy, do you use minus or plus cylinder form? PMID- 8481381 TI - Inhibition of electron transport of rat-liver mitochondria by synthesized antimycin A analogs. AB - A series of antimycin A analogs was synthesized by replacement of a dilactone ring moiety of natural antimycin A by various alkyl, substituted phenyl, substituted diphenyl ether, or amino acid ester groups. The structure-inhibitory activity relationship was studied with rat-liver mitochondria to identify roles of the dilactone-ring moiety in the inhibitor binding to a Qi reaction center of cytochrome bc1 complex. All derivatives caused further reduction of cytochrome b reduced by succinate and the oxidant-induced reduction, showing that the derivatives inhibited electron transport by interacting with a Qi reaction center. The inhibition tended to increase as the hydrophobicity of the inhibitor increased. The mode of binding of inhibitor molecules to a Qi center, which was reflected in, for example, a sigmoidal titration curve for respiratory inhibition and a time-dependent change in inhibitory activity, varied depending on structure. These results suggested that the role of the dilactone-ring moiety of antimycin A may be not only to support hydrophobic interaction with the binding domain by increasing the hydrophobicity of the molecule, as proposed earlier, but also to regulate close fitting of the salicylic acid moiety to the binding domain. PMID- 8481382 TI - Primary structure, deduced from cDNA, secondary structure analysis and conclusions concerning interaction surfaces of the delta subunit of the photosynthetic ATP-synthase (E.C. 3.6.1.34) from millet (Sorghum bicolor) and maize (Zea mays). AB - Lambda gt11 cDNA clones for the nuclear-encoded subunit delta of the chloroplast ATP-synthase from Zea mays and Sorghum bicolor were sequenced. The processing site for S. bicolor delta was established, and the sequence of the mature subunit delta from Z. mays was completed by N-terminal sequencing of the proteins isolated from chloroplasts. Only five amino acids are identical and not more than 16% conservatively exchanged in all sequences of delta subunits from higher plants and the corresponding proteins from alga, bacteria and mitochondria (OSCP) available. In binary comparison the comparatively high conservation of hydrophilic residues indicates the importance of the surface of delta. The degree in identities of surface residues correlates with the capacity in hybrid reconstitution of photophosphorylation. A hypothetical secondary structure model for a typical delta subunit can be deduced from prediction algorithms. Three putative amphipathic alpha helices and an antiparallel amphipathic beta sheet seem to be conserved. These common secondary structure features should be significant for the function of the delta subunit of F0F1 ATPases. PMID- 8481383 TI - Identification of an exchangeable non-catalytic site on mitochondrial F1-ATPase which is involved in the negative cooperativity of ATP hydrolysis. AB - Labeling of mitochondrial F1-ATPase with 8-azido-ATP or 8-azido-ADP under turnover conditions with Mg(2+)-ATP resulted in the identification of one exchangeable non-catalytic site whose occupation with a ligand does not influence the ATPase activity of F1 when measured at Vmax. With 8-azido-ADP two exchangeable non-catalytic sites could be labeled, but at one of them the bound ligand exchanges, at least partly, during the illumination under turnover conditions. After labeling an exchangeable non-catalytic site under turnover conditions with 8-azido-ATP or with 8-azido-ADP, F1-ATPase kept the ability to bind NAP3-2N3ADP at the slowly exchangeable noncatalytic site, thereby inhibiting the ATPase activity by 45%, as recently described (Edel et al. (1992) Biochim. Biophys. Acta 1101, 329-338). Covalent modification of the low-affinity non catalytic site with 8-nitreno-AT(D)P increased the Km of ATP and abolished the negative cooperativity of ATP hydrolysis. This site can therefore be marked as a regulatory site, whose occupation with a nucleotide decreases the affinity of the catalytic sites for ATP. PMID- 8481384 TI - Lipid composition of the vacuolar membrane of Acer pseudoplatanus cultured cells. AB - Tonoplast was prepared by osmotic lysis of a pure vacuolar fraction isolated from protoplasts derived from Acer pseudoplatanus cultured cells. After their extraction, neutral and polar lipids were separated by a thin layer chromatography. Phospholipids, glycolipids and neutral lipids represented 44.5%, 39.1% and 16.4% of total lipids, respectively. Sterols (glycosylated plus non glycosylated forms) constituted 30.8% of total lipids; 75% of sterols were glycosylated. The most prominent lipids were phosphatidylethanolamine (20.8%), phosphatidylcholine (13.5%), ceramide monohexoside (12.8%), steryl glycoside (12.2%) and acylated steryl glycoside (10.9%). Glucose was the only sugar released by acid hydrolysis of these three later compounds. The major neutral lipids were free sterols, triacylglycerols and steryl esters. The phospholipid composition was characterised by a high content of phosphatidylethanolamine (50% more than phosphatidylcholine). The fatty acid composition of phospholipids revealed two major components: palmitic and linoleic acids; they accounted together for 60 to 80% of fatty acids. When tonoplast was incubated at pH 5.5 with 5 mM Ca2+, the free fatty acid content (12% of neutral lipids) increased by 10% and lysophospholipids were detected. This indicated the presence of a calcium dependent phospholipase A2 associated with the tonoplast. PMID- 8481385 TI - Octadecatetraenoate synthesis in the unicellular alga Isochrysis galbana: studies with intact and broken chloroplasts. AB - (1) Monogalactosyldiacylglycerol (MGD) is the major lipid component of Isochrysis galbana. In cells incubated for 3 h with [1-14C]]acetate or [1-14C]oleate. MGD contained 35.9% and 52.8%, respectively, of the label incorporated into cellular lipids. (2) 18:4 amounted to 50-60% of the total FA of MGD. Separation of MGD species of cells grown with [1-14C]oleate on AgNO3 impregnated plates revealed 20 distinct spots. The slowest spot was identified as dioctadecatetraenoyl MGD. Fast moving species were enriched with 18:1. (3) In cells incubated for 3 h with [1 14C]oleate, approx. 60% of the radioactivity was associated with 18:1. Subsequent chase resulted in a gradual shift of label and after 48 h [14C]18:1 declined to 10% and [14C]18:4 reached 52%. This shift was also reflected in the labeling pattern of the MGD-species. Dioctadecatetraenoyl-MGD became labelled only after 24 h. (4) Addition of the substituted pyridazinone herbicide (SAN 9785) during the chase period inhibited [14C]18:4 formation; [14C]18:2 and [14C]18:3 accumulated instead. (5) Isolated chloroplast readily incorporated [14C]oleate into MGD and PA. Considerable amounts of [14C]18:1 were desaturated to 18:2 and 18:3. Only very small amounts of 18:4 were formed. O2 was required for desaturation. Cofactor requirement could not be shown. (6) Membranes isolated from broken chloroplasts retained the ability to incorporate [14C]oleate into MGD and PA and desaturate 18:1 to 18:2 and 18:3. PMID- 8481386 TI - In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) to apolipoprotein AI in rabbits. AB - In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) from E. coli to apolipoprotein (apo) AI was investigated. rh-Met-proapo AI was labeled with 125I, and then administered intravenously to rabbits. Blood was sampled periodically for 6 days. The plasma decay curves of radioiodinated rt-Met proapo AI were similar to those of human mature apo AI (fractional catabolic rate (FCR); 1.018 +/- 0.090/day vs. 0.976 1 0.031/day, respectively). In vivo conversion of rh-Met-proapo AI to mature apo AI was examined by autoradiography of the isoelectric focusing (IEF) slab gel, i.e., the HDL fraction from each sampling point was semiquantitatively applied to IEF. It was found that the radioactivity of rh-Met-proapo AI migrated to more acidic isoproteins, the conversion was complete within 24 h, and the FCR of rh-Met-proapo AI was 9.20 +/- 1.34/day. Although the plasma decay curves of both human pro (rh-Met-proapo AI) and mature apo AI were significantly steeper than those of rabbit mature apo AI4 and apo AI5 (FCR; 0.703 +/- 0.027/day and 0.795 +/- 0.031/day, respectively), the conversion rate of human rt-Met-proapo AI to mature apo AI in rabbit was assumed to be 1:1. In vitro incubation of rh-Met-proapo AI with rabbit serum produced mature apo AI isoproteins, as determined by the apo AI immunoblotting method. Prediction of the amino acid sequence at the NH2 terminus of rabbit proapo AI showed that the prosegment consisted of an alpha helix with a high probability of a beta turn at Pro9, which is close to that in humans. Thus, (1) the proteolytic cleavage of proapo AI is an extracellular event, (2) the converting enzyme in rabbits can also process human proapo AI, (3) this converting enzyme does not specifically and directly attack the Gln6-Asp7 bond which links the carboxyl terminal residue of the hexapeptide to the amino-terminal residue of human mature apo AI. The conformation of proapo AI at the NH2 terminus (alpha helix of the prosegment and a beta turn at Pro9) may have a key role in this cleavage, and (4) the examination of rh-Met-proapo AI in rabbits helps to explain the early events of HDL biogenesis. PMID- 8481387 TI - Adsorption, compression and stability of surface films from natural, lipid extract and reconstituted pulmonary surfactants. AB - A pulsating bubble surfactometer was used to study the surface activities and surface film stabilities of bovine pulmonary surfactants (10 mg/ml) and a reconstituted surfactant (10 mg/ml). Pulmonary surfactants were natural surfactant (NS), lipid extract surfactant [LES(chol)] and lipid extract surfactant without neutral lipids (LES). NS is composed of phospholipids, neutral lipids and surfactant-associated proteins (SP-A, SP-B and SP-C). Both LES(chol) and LES are organic solvent extracts of NS. LES(chol) retains all the components of NS except SP-A. Reconstituted surfactant was dipalmitoylphosphatidylcholine (DPPC): 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG): SP-B/7:3:1%. All three pulmonary surfactants attained the equilibrium surface tension almost instantaneously at 37 degrees C. The adsorption rates of NS and LES(chol) at 24 degrees C were similar to those at 37 degrees C, while LES exhibited a lower adsorption rate at 24 degrees C. Reconstituted surfactant adsorbed slower than any of the pulmonary surfactants. Film stability was studied by recording the spontaneous increase in the pressure gradient of a static bubble at the minimum size (Rmin) once near zero surface tension was attained. The order of surface film stabilities were: reconstituted surfactant > > NS > LES > LES(chol). Surface films of NS and LES could be stabilized by prolonged pulsation, while film stability of LES(chol) was only moderately affected by pulsation. These results indicate that SP-A in NS promotes formation of some unique structure, possibly tubular myelin, which induces selective adsorption of lipids into the surface. PMID- 8481388 TI - Metal ion and salt effects on the phospholipase A2, lysophospholipase, and transacylase activities of human cytosolic phospholipase A2. AB - Human cytosolic phospholipase A2 (cPLA2) is an arachidonic acid specific enzyme which may play a role in arachidonic acid release, eicosanoid production, and signal transduction. The PLA2 activity of this enzyme is stimulated by microM levels of Ca2+. Using a pure recombinant enzyme, we have confirmed that cPLA2 is not absolutely dependent on Ca2+, since Sr2+, Ba2+ and Mn2+ also gave full enzyme activity. Heavy metals, in contrast, inhibited enzyme catalysis suggesting the involvement of an essential cysteine residue. In the absence of Ca2+, high salt concentrations overcame the requirement for divalent metals, indicating that Ca2+ is not required for PLA2 catalytic activity. cPLA2 also displays a lysophospholipase (lyso PLA) activity with lysophosphatidylcholine micelles as a substrate. Unlike the PLA2 activity, the lyso PLA activity toward these micelles is not stimulated by Ca2+. However, upon the addition of glycerol or Triton X-100 to the assay, Ca2+ activation is observed, indicating that substrate presentation can affect the apparent Ca2+ dependence. Glycerol was found to be a potent stimulator of lyso PLA activity and specific activities up to 50 mumol min-1 mg-1 were observed. In addition to the PLA2 and lyso PLA activities, we report that cPLA2 displays a relatively low, CoA-independent transacylase activity which produces phosphatidylcholine from lysophosphatidylcholine substrate. The observation of this novel transacylase activity is consistent with the formation of an acyl-enzyme intermediate. PMID- 8481389 TI - Competitive inhibition of lipolytic enzymes. IX. A comparative study on the inhibition of pancreatic phospholipases A2 from different sources by (R)-2 acylamino phospholipid analogues. AB - The inhibitory power (Z) of a number of (R)-1-alkyl-2-acylamino phospholipid analogues was determined for three mammalian phospholipases A2 from pig, ox and horse pancreas. All three enzymes display a clear preference for anionic (phosphoglycol) inhibitors over the zwitterionic (phosphocholine) derivatives; this effect is most pronounced for the bovine enzyme. Upon variation of the 1 alkyl chain length, the bovine and equine phospholipases, like the porcine enzyme in previous studies, show an optimum in Z for a six-carbon alkyl group. The introduction of a double bond in the 2-acylamino group generally improves the inhibitory power as compared with a fully saturated acyl chain. For the horse enzyme, the presence of an (R)-2-undecenoylamino group in the phosphocholine- and phosphoglycol-containing inhibitors resulted in affinities which are nearly 4 and 5 orders of magnitude higher, respectively, than for the substrate molecule. Direct determination of the dissociation constant Ki* of several inhibitors incorporated in a host lipid/water interface of non-inhibitory n octadecenylphosphocholine micelles, was performed by ultraviolet difference spectroscopy. The progressive binding of a single inhibitor molecule into the active site of the three enzymes was followed quantitatively by an increasing tyrosine perturbation. With moderately strong competitive inhibitors (Z values ranging from about 50 to 10,000), quantitative values for Ki* were obtained. Extrapolation of the experimentally found linear relationship between Z and 1/Ki* yields predicted Ki* numbers for the much stronger inhibitors with Z values between 10,000 and 100,000. PMID- 8481390 TI - Kinetics of the interaction of amphipathic alpha-helical peptides with phosphatidylcholines. AB - The rate of association of three amphipathic alpha-helical peptides with phosphatidylcholine liposomes was examined to provide more detailed information on the relationship between peptide length and the kinetics of lipid interactions. When added to dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC) liposomes from a guanidine-HCl solution, a ten residue peptide rapidly decreased the turbidity of the liposomes. However, a related 17-residue peptide had only a minimal effect on liposome turbidity. A 14 residue peptide was intermediate in effectiveness. Similarly, when liposomes were added to peptides dissolved in an aqueous buffer, the ten residue peptide but not the 17-residue peptide cleared the turbid liposomes and the 14-residue peptide was intermediate in efficacy. The rate of binding to the liposomes was compared with the three peptides by measurements of the kinetics of energy transfer from the single tryptophan residue of the peptides to a fluorescent probe in the bilayer interior. The tryptophan residue of the ten residue peptide effectively transferred energy to the probe, while that of the 14-residue peptide was less effective. Little or no energy transfer was observed with the 17-residue peptide. The binding of the 10 residue peptide was rapid and complete within < 100 ms. The 14-residue peptide bound more slowly, but still within seconds. The time frames for binding are an order of magnitude shorter than those observed for lipid clearing. The relationship between peptide length, liposome clearing and lipid binding kinetics is discussed in terms of a possible competing peptide-peptide interaction in the aqueous phase and a slow rearrangement of the lipid bilayer. PMID- 8481391 TI - Incorporation of stearic acid (18:0) and palmitic acid (16:0) in phospholipid molecular species studied in isolated rat liver cells. AB - The incorporation of [1-14C]16:0 and [1-14C]18:0 in the molecular species of PC and PE in isolated rat liver cells was studied. More [14C]18:0 than [14C]16:0 was esterified both in PC and PE. Also the chain elongated and desaturated products (16:1, 18:0 and 18:1) were incorporated. The main molecular phospholipid species formed from [14C]18:0 were 18:0-18:2, 18:0-20:4 and 18:0-22:6. 18:0-18:0 species was not detected, independent of the substrate concentration (0.1-0.9 mM). With [14C]16:0 at low substrate concentration (0.1 mM) the dominating species are 16:0 18:2, 16:0-20:4 and 16:0-22:6. These species were detected already after 10 min. The same main species are formed both in PC and PE, but the relative amounts differ. In PC the combination with 18:2 is most abundant for both saturated fatty acid substrates. In PE 18:0-20:4 dominates when 18:0 is the substrate, and 16:0 22:6 when 16:0 is. At higher substrate concentrations (0.4-0.9 mM) 16:0 is also esterified in 16:0-16:0. This molecular species is efficiently degraded in the cells within 2-3 h, in contrast to the other species formed. The results suggest that 16:0 and 18:0 are directly incorporated in the sn-1 position in physiologically important phospholipid molecular species. With an excess of 16:0, 16:0-16:0 is also formed in substantial amounts, but this uncommon species is thereafter removed. PMID- 8481392 TI - Inhibition of oxidized low-density lipoprotein metabolism in macrophage J774 by helvolic acid. AB - The antibiotic helvolic acid inhibited cholesteryl ester accumulation in macrophage J774 treated with oxidized low-density lipoprotein (LDL) at a concentration of 50-350 microM. The agent reduced oxidized 125I-LDL degradation and [14C]oleate incorporation into cholesteryl ester. In a cell-free assay, ATP dependent acidification of endosomes and lysosomes was significantly inhibited by 35 microM helvolic acid, suggesting that this activity accounts for the inhibition of oxidized LDL metabolism in the macrophages. PMID- 8481393 TI - Characterization of the in vitro conversion of dolichol to dolichoate in bovine thyroid. AB - The enzymic conversion of dolichol into dolichoic acid has been studied in bovine thyroid subcellular fractions using [1-3H]dolichol as a substrate. The presence of conversion activity could be demonstrated in both the mitochondrial- and supernatant fractions. Investigation of cofactor requirements revealed that NAD+ was essential for reaching optimal activity. From kinetic studies Km-values of 3.5-4 microM and 0.29 mM could be calculated for, respectively, dolichol and NAD+ using the mitochondrial fraction as an enzyme source. No inhibitory effects from ethanol or pyrazole were detected suggesting that alcohol dehydrogenase is not involved in the dolichol-->dolichoate conversion as observed in a bovine thyroid mitochondrial fraction. From inhibitor studies the conversion system behaves distinctly differently from the NADP(+)-depending microsomal oxidoreductase as well as from catalase. The conversion activity in the supernatant on the other hand must be ascribed, at least partially, to a side activity of alcohol dehydrogenase. PMID- 8481394 TI - Preparation and characterization of spheroidal, reconstituted high-density lipoproteins with apolipoprotein A-I only or with apolipoprotein A-I and A-II. AB - This study describes the preparation of spheroidal reconstituted HDL which contain apolipoprotein (apo) A-I only, (A-I w/o A-II) r-HDL, or apo A-I and apo A II, (A-I w A-II) r-HDL. Spheroidal (A-I w/o A-II) r-HDL with diameters of 8.0, 9.2 and 11.2 nm were prepared by incubating discoidal (A-I w/o A-II) r-HDL with lecithin-cholesterol acyltransferase and low-density lipoproteins. Spheroidal (A I w A-II) r-HDL were prepared by displacing apo A-I from spheroidal (A-I w/o A II) r-HDL with apo A-II. Modification with apo A-II did not significantly affect the diameters of the 8.0 and 9.2 nm (A-I w/o A-II) r-HDL. When, however, apo A-II was added to the (A-I w/o A-II) r-HDL of diameter 11.2 nm, the size of the particles decreased to 9.4 nm. To determine whether modification of (A-I w/o A II) r-HDL with apo A-II altered the structure of the r-HDL, the packing of phospholipids in the modified and unmodified particles was compared by steady state fluorescence polarization and the environments of the apo A-I tryptophan residues in (A-I w/o A-II) and (A-I w A-II) r-HDL were compared by fluorescence spectroscopy. The results of these studies suggested that modification of spheroidal (A-I w/o A-II) r-HDL with apo A-II alters the environment of apo A-I tryptophan residues in small, but not large, r-HDL and does not affect the packing of phospholipids. PMID- 8481395 TI - Is there a specific lysophospholipase in human pancreatic juice? AB - The existence of a specific lysophospholipase in human pancreatic juice was evaluated. The proteins were separated by a series of chromatographic steps including Sephacryl S-200, cholate-Sepharose 4B, Sephadex G-100 and CM-Sephadex G 50. The enzyme activities against 1-palmitoyl lysolecithin (LL) as well as tributyrin (TB) and p-nitrophenyl butyrate (PNPB) were determined in all the fractions of these purification procedures. Enzyme activity against LL was always eluted in parallel with activities against TB and PNPB, and no unique activity against LL could be found. The specific activity against LL was 40-times lower than that against PNPB and 200-times lower than that against TB. It is concluded that there is no unique lysophospholipase in human pancreatic juice and that the hydrolysis of lysolecithin is most likely performed by carboxyl ester lipase. PMID- 8481396 TI - The interaction between beta-carotene and lipoxygenase in plant and animal systems. AB - The effect of beta-carotene (BC) on the activity of lipoxygenase (LOX) from plant and animal sources has been examined. Soybean lipoxygenase L-2 activity towards linoleate was inhibited by BC by a maximum of 70% at pH 6.5, whereas L-1 activity was little affected at pH 9.0. Lineweaver-Burk plots indicated that BC inhibited LOX activity by mixed competitive/non-competitive mechanisms. Other hydrophobic compounds also inhibited LOX activity; oleic acid and retinol were competitive inhibitors whereas tocopherol acetate and 5,8,11,14-eicosatetraynoic acid (ETYA) were non-competitive inhibitors. Binding studies with L-2 LOX bound to Sepharose indicated BC-binding and inhibition with the immobilized LOX. Activity of LOX from animal sources was also inhibited by BC both towards linoleate and arachidonate. PMID- 8481397 TI - Regulation of synthesis of lactosylceramide in normal and tumor proximal tubular cells. AB - We have measured the binding and degradation of low-density lipoprotein (LDL) and LDL-mediated effects on cholesteryl ester (CE) synthesis in cultured normal and tumor proximal tubular (PT) cells. The effects of LDL on the regulation of glycosphingolipid metabolism in cells was pursued employing radioactive precursors, e.g., [3H]serine, and [3H]glucose and by measuring the activity of UDP-galactose: glucosylceramide: B1-4 galactosyltransferase (GalT-2). In normal PT cells, there was a saturable and displaceable binding and degradation of 125I LDL and a LDL mediated 14-fold stimulation of cholesteryl ester (CE) synthesis. This was accompanied by a suppression (70-80%) of incorporation of [3H]glucose and [3H]serine into GlcCer, LacCer, GbOse3Cer and GbOse4Cer and suppression (70 80%) of GalT-2 activity. In tumor PT cells, displaceable binding and degradation of 125I-LDL was not observed and LDL failed to stimulate CE synthesis. In such cells, LDL exerted a concentration-dependent stimulation of [3H]glucose and [3H]serine incorporation into GSL. Maximum stimulation (250%) of GalT-2 activity in tumor PT cells occurred with 25 micrograms LDL/ml medium. We conclude that LDL taken up via receptor mediated pathway decreases GaIT-2 activity in normal PT cells. In contrast, LDL not taken up via the LDL receptor pathway in tumor PT cells failed to suppress the incorporation of [3H]glucose and [3H]serine into glycosphingolipids and GalT-2 activity leading to a stimulation of lactosylceramide synthesis. PMID- 8481398 TI - Reaction of aspirin with cysteinyl residues of lens gamma-crystallins: a mechanism for the proposed anti-cataract effect of aspirin. AB - Incubation of lens crystallins with aspirin inhibits the development of opacities caused by cyanate. Cyanate-induced opacities are thought to be due to carbamylation of the lysyl residues which causes a decrease in the protein charge and subsequent conformational changes that permit disulfide bonding. Because aspirin can also react with lysyl residues, it has been proposed that the aspirin inhibition of cataractogenesis is due to acetylation of the lysyl residues which would block their reaction with cyanate. However, acetylation of lysyl residues also lowers the protein charge and would be expected to effect changes in protein conformation similar to those caused by carbamylation. Therefore, acetylation of the lysyl residues is not a satisfactory explanation for the inhibitory effect of aspirin on lens opacification. Our investigations of the reactions of cyanate and aspirin with bovine gamma II-crystallins show that the cysteinyl residues are also carbamylated and acetylated at pH 7.4. At this pH, the carbamylation at the cysteinyl residues is reversible, leading to regeneration of the thiol group and disulfide bonding. In contrast, the acetylation at cysteinyl residues is stable at pH 7.4 and can prevent disulfide bonding. This difference in stability explains how cyanate promotes, and aspirin inhibits, cataractogenesis. PMID- 8481399 TI - Phospholipid synthesis in the lymphomatous mouse liver studied by 31P nuclear magnetic resonance spectroscopy in vitro and by administration of 14C radiolabelled compounds in vivo. AB - High phosphomonoester to ATP ratios have been found in 31P magnetic resonance spectra from livers of patients with hepatic lymphoma (Dixon et al. (1990) Br. J. Cancer 63, 953-958). The present study of a murine lymphoma showed that the phosphomonoester in the lymphomatous liver was largely phosphoethanolamine, which is an intermediate of phospholipid metabolism. A significant positive correlation was found between the concentration of phosphoethanolamine, measured by high resolution 31P nuclear magnetic resonance spectroscopy of extracts, and the degree of infiltration, assessed by quantitative histology. The phosphoethanolamine concentration reached about 10 times its normal level, but the phosphocholine concentration remained the same as in the normal liver. Radiolabelling studies showed that while the rate of phosphoethanolamine synthesis from exogenous [14C]ethanolamine was higher in the lymphomatous mouse liver than in control livers, the rate of phosphatidylethanolamine synthesis was lower in the lymphomatous liver. The rate of phosphatidylcholine synthesis in lymphoma-bearing livers was not significantly different from that in control mouse livers. PMID- 8481400 TI - Comparison of baculovirus-expressed c-Abl and BCR/ABL protein tyrosine kinases. AB - Mouse c-Abl type IV and human BCR/ABL proteins have been expressed in insect cells using the baculovirus system. The proteins were expressed as full-length polypeptides as judged by electrophoresis in denaturing gels. They were identified by immunoprecipitation and immunoblotting with antibodies against ABL peptides and, for BCR/ABL, against a BCR peptide. In these immunoprecipitates both proteins gave autophosphorylation principally on tyrosine. Both proteins were active tyrosine kinases, phosphorylating a variety of tyrosine-containing substrates. In fresh extracts both proteins contained phosphotyrosine as shown by Western blots with antiphosphotyrosine antibodies. Partial purification could be achieved readily using ion exchange columns, and the BCR/ABL protein, p210BCR/ABL, could be further purified to near-homogeneity using an antiphosphotyrosine column. Both enzymes required a divalent metal ion for activity. At low concentrations of ATP (2 microM) and with angiotensin II as substrate both enzymes were activated by Mn2+ or by Mg2+. No major differences in catalytic properties were found between the two isolated enzymes in solution. The oncogenic properties of p210BCR/ABL may be due to its different subcellular location, or to the presence of an intracellular inhibitor of c-Abl that does not inhibit BCR/ABL, or to altered substrate-specificity such that it can phosphorylate a unique substrate which is not recognised by c-Abl. PMID- 8481401 TI - Rapid screening method of abnormal insulin-receptor gene expression: allele specific oligonucleotide hybridization by using silent polymorphisms. AB - An asymmetrical reduction in the levels of the insulin receptor mRNA transcribed from one allele was reported in some patients with severe insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). To detect this abnormality, we designed the less laborious method; Allele-specific oligonucleotide hybridization of the amplified mRNA (cDNA) by using silent polymorphisms in the insulin receptor gene (nucleotide positions at 1686 and 1698). The allelic frequencies of C-1686 and T-1686 were 0.63 and 0.37, respectively (0.60 and 0.40 in 10 normal subjects, and 0.67 and 0.33 in 20 NIDDMs; n.s.). Similarly, the allelic frequencies of A-1698 and G-1698 were 0.47 and 0.53, respectively (0.50 and 0.50 in the normal subjects, and 0.45, and 0.55 in the NIDDMs; n.s.). These results suggest that these two polymorphisms are very common in Japanese. Nineteen (64%) out of 30 cases are heterozygous at one or two position(s), suggesting that it is possible to distinguish the mRNA transcribed from each of two alleles of the insulin receptor gene with using allele-specific oligonucleotide hybridization. Although we successfully measured the ratio of mRNA expression from two alleles of the gene in 20 NIDDMs, there was no patient whose mRNA transcribed from one allele of the insulin receptor gene was extremely decreased. We showed that allele-specific oligonucleotide hybridization method is useful for the screening of abnormal insulin-receptor gene expression. PMID- 8481402 TI - Effect of increased gene dosage expression on the alpha-interferon receptors in Down's syndrome. AB - The gene coding for the alpha, beta-interferon (alpha, beta-IFN) receptor is localized to chromosome 21. Cells from patients with Down's syndrome contain an extra chromosome 21, and thereby an expected 1.5-times increase in the number of genes located to this chromosome and in consequence a 1.5-times increase in cell surface alpha-IFN receptors. Actual measurements of these by competition binding experiments with human recombinant alpha-IFN on peripheral blood mononuclear cells (PBMC) from patients with Down's syndrome resulted in a mean of 1.69, which is in accordance to the theoretical 1.50, but slightly overestimated due to the calculation method. The increased gene dosage of the alpha-IFN receptor was quantitatively verified by Southern blot-hybridizations. Further characterization of alpha-IFN receptor binding showed insignificant differences in dissociation constants among patients and healthy individuals. PMID- 8481403 TI - Glomerular thromboxane A2/prostaglandin H2 receptors: characterization and effect of adriamycin-induced nephrotic syndrome. AB - We have characterized the thromboxane (TX) A2/prostaglandin (PG) H2 receptor in glomeruli isolated from the rat using the agonist radioligand [125I]-BOP. Binding of [125I]-BOP was highly specific, stereoselective, and to a single class of high affinity binding sites (Kd = 1.16 +/- 0.22 nM and Bmax = 348 +/- 32 fmol/mg protein; n = 6). Binding of [125I]-BOP was competed for by the agonist ONO11113 (Kd = 50.8 +/- 8.0 nM; n = 4) and the antagonists SQ29548 (Kd = 15.8 +/- 1.0 nM; n = 3), L657925 (Kd = 12.1 +/- 2.2 nM; n = 3) and L657926 (Kd = 1642 +/- 135 nM; n = 3). I-BOP also produced a TXA2/PGH2 receptor-mediated rise in [Ca2+]i in isolated glomeruli In adriamycin-induced nephrotic syndrome in the rat, the development of proteinuria is reported to be dependent on increased renal TXA2 production. We therefore examined whether or not changes in glomerular TXA2/PGH2 receptors occur between control and nephrotic rats. No changes in expression or affinity of either glomerular or platelet TXA2/PGH2 receptors were observed. Kd and Bmax values for isolated glomeruli were 1.45 +/- 0.24 nM and 406 +/- 72 fmol/mg for controls and 1.22 +/- 0.25 nM and 321 +/- 62 fmol/mg for nephrotic rats (n = 6). PMID- 8481404 TI - Applications of biotinylated V3 loop peptides of human immunodeficiency virus type 1 to flow cytometric analyses and affinity chromatographic techniques. AB - A principal neutralizing determinant of human immunodeficiency virus type 1 (HIV 1) lies within the V3 loop of gp120, the external major envelope glycoprotein. V3 loop peptides derived from two HIV-1 strains, HTLV-III BH-10 (V3-BH10) and LAVELI (V3-ELI), were synthesized and biotinylated. The binding of both biotinylated V3 BH10 and V3-ELI to the surfaces of MOLT-4 clone 8 cells was demonstrated by flow cytometric analyses. Both the peptides (more than 2 microM) bound to the cells (2 x 10(5) in a dose-dependent manner. The binding of biotinylated V3-BH10 was specifically inhibited by a neutralizing monoclonal antibody (0.5 beta). The binding of both of the biotinylated V3 loop peptides was enhanced by the addition of unlabeled V3-BH10. In addition, the peptides were employed as ligands on affinity columns. A major V3 loop binding protein (V3BP) was purified from the membrane soluble fraction of MOLT-4 cells by successive application to two different V3 loop columns. V3BP consisted of two major polypeptides (32 and 33 kDa). The SDS-PAGE profile of V3BP did not change under non-reducing conditions, but only a single band was observed after analysis on native PAGE. The major peak of the eluate as determined by size exclusion chromatography was broad and the estimated relative molecular mass was much larger than 33 kDa, suggesting that V3BP comprises several subunits. Taken together, we confirmed that the V3 loop peptides are useful in the characterization of V3BP(s) of which they are conformational ligands. PMID- 8481405 TI - Decreased catalase activity is the underlying mechanism of oxidant susceptibility in glucose-6-phosphate dehydrogenase-deficient erythrocytes. AB - Historically, it has been theorized that the enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes arises as a direct consequence of an inability to maintain cellular glutathione (GSH) levels. This study alternatively hypothesizes that decreased NADPH concentration leads to impaired catalase activity which, in turn, underlies the observed oxidant susceptibility. To investigate this hypothesis, normal and G6PD-deficient erythrocytes and hemolysates were challenged with a H2O2-generating agent. The results of this study demonstrated that catalase activity was severely impaired upon H2O2 challenge in the G6PD-deficient cell while only a transient decrease was observed in normal cells. Supplementation of either normal or G6PD-deficient hemolysates with purified NADPH was found to significantly (P < 0.001) inhibit catalase inactivation upon oxidant challenge while addition of NADP+ had no effect. Analysis of these results demonstrated direct correlation between NADPH concentration and catalase activity (r = 0.881) and an inverse correlation between catalase activity and erythrocyte oxidant sensitivity (r = 0.906). In contrast, no correlation was found to exist between glutathione concentration (r = 0.170) and oxidant sensitivity. Analysis of NADPH/NADPt ratio in acatalasemic mouse erythrocytes demonstrated that NADPH maintenance alone was not sufficient to explain oxidant resistance, and that catalase activity was required. This study supports the hypothesis that impaired catalase activity underlies the enhanced oxidant sensitivity of G6PD-deficient erythrocytes and elucidates the importance of NADPH in the maintenance of normal catalase activity. PMID- 8481406 TI - The activity of wheat gliadin peptides in in vitro assays for coeliac disease. AB - A fraction of a peptic-tryptic-pancreatinic digest of wheat gliadin (fraction 9), known to be toxic to individuals with coeliac disease, together with synthetic peptides containing key gliadin sequences, were tested for their effects on foetal chick intestine and on rat liver lysosomes. Fraction 9 and a dodecapeptide corresponding to residues 75-86 of A-gliadin (RPQQPYPQPQPQ) were the only peptides to display appreciable activity in both assays. A synthetic hexapeptide corresponding to residues 77-82 was only weakly toxic to lysosomes and non-toxic to chick duodenum. A decapeptide corresponding to residues 76-85 was non-toxic in both assays. Two serine-containing peptides containing the key sequence PSQQ were also tested but were found to be non-toxic, as was the hexapeptide PSQQQP. The results suggest that the key sequences QQQP and PSQQ are not sufficient by themselves to cause activity. Further tests on synthetic peptides will be necessary to define the sequences of highest toxicity. PMID- 8481407 TI - Isolation and purification of a squamous cell carcinoma of the head and neck associated antigen identified by autologous antibody. AB - We have previously shown that detection of autologous antibody activity to squamous cell carcinoma of the head and neck may be augmented by dissociation of immune complexes. Western blot analysis with autologous antibody has identified a 60 kDa squamous cell carcinoma of the head and neck-associated antigen in spent media and immune complex-dissociated serum ultrafiltrate not recognized by normal human sera. Antigen-containing fractions of spent media were eluted from anion exchange columns immediately after serum albumin indicating that the antigen has an acidic pI < 4. Preparative purification of the squamous cell carcinoma antigen was accomplished by anion exchange of concentrated spent media (protein concentration 300 mg/ml) followed by lectin affinity chromatography with a Triticum vulgaris column. A single 60 kDa band was detected by silver stain and Western blot in antigen-containing fractions eluted following lectin affinity chromatography and SDS-PAGE. Final concentration of the antigen was determined to be 1 microgram/ml of protein with relative activity increased 1600 x over unfractionated spent media. We conclude that a squamous cell carcinoma of the head and neck-associated antigen, detected by autologous antibody, is an acidic 60 kDa glycoprotein. PMID- 8481409 TI - Study of intracellular deposition of the anti-leprosy drug clofazimine in mouse spleen using laser microprobe mass analysis. AB - Laser microprobe mass analysis (LAMMA) was used to study the composition of the brick-red crystalline material which had accumulated in the spleen of mice that had received the anti-leprosy drug Clofazimine in their diet for several months. The crystalline deposits light-microscopically resembled pure Clofazimine crystals. The presence of the drug in the crystals was indicated by LAMMA by the appearance of the chloride mass peaks in the negative mass spectra. More specific information was obtained from the positive mass spectra. A mass signal for the protonated molecule was present. PMID- 8481408 TI - A novel mutation in erythropoietic protoporphyria: an aberrant ferrochelatase mRNA caused by exon skipping during RNA splicing. AB - An aberrant ferrochelatase mRNA lacking exon 10 was found in a patient with erythropoietic protoporphyria (EPP). In her genomic DNA an A-->T transversion at position -3 of the donor site of intron 10 appeared to be responsible for the exon skipping. Both the patient and her sister were heterozygous for this mutation. PMID- 8481410 TI - Identification with liquid chromatography-ionspray mass spectrometry of the metabolites of the enantiomers N-methyl dextrorphan and N-methyl levorphanol after rat liver perfusion. AB - To gather more information on stereochemical factors in the hepatic disposition of organic cations, mass spectrometry coupled to liquid chromatography was used to determine the identity of the metabolites excreted in bile after isolated rat liver perfusions with the quaternary ammonium derivatives of the enantiomeric drugs dextrorphan and levorphanol. Ionspray mass spectrometry was chosen for its soft ionization and absence of thermal degradation of labile compounds. The drugs were labelled with a stable (2H) isotope and mixed with unlabelled drugs to create an artificial isotope pattern in the mass spectrum and facilitate the recognition of unknown metabolites. In mass spectra that were recorded under normal conditions, fragmentation was absent and metabolites of N-methyl dextrorphan and N-methyl levorphanol were visible as parent-ion 'doublets'. Collision-induced fragmentation studies were performed to support the identification of the metabolites. For N-methyl dextrorphan the glucuronide, the glutathione conjugate and the glucuronide of the N-demethylated metabolite were found in bile. For N-methyl levorphanol the glucuronide, the glutathione conjugate, the sulphate conjugate and the glucuronide of a hydroxylated N-methyl levorphanol were excreted in bile. Thus a remarkable stereoselectivity occurs in the metabolism of these quaternary ammonium compounds in the rat liver. PMID- 8481411 TI - Determination of amphetamine, methamphetamine and desmethyldeprenyl in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry. AB - A sensitive and specific assay for the quantitative determination of amphetamine, methamphetamine and desmethyldeprenyl in human plasma specimens is described. Electron capture/negative ion chemical ionization gas chromatography/mass spectrometry is used to determine the extracted plasma concentrations of the three target compounds as their N-heptafluorobutyryl derivatives. Quantitation is performed by stable isotope dilution using d6-amphetamine and d6-methamphetamine as internal standards. Selected ion monitoring of the [M-HF]- ions of both the analytes and internal standards results in minimum quantifiable limits of 0.10 ng ml-1 for both amphetamine and methamphetamine and 0.25 ng ml-1 for desmethyldeprenyl. Excellent linearity (r = 0.998) up to at least 5.00 ng ml-1 is demonstrated. PMID- 8481412 TI - Electrospray ionization of selected low-molecular-weight natural biotoxins. AB - Electrospray ionization (ESI) spectra were acquired for several low-molecular weight marine and freshwater biotoxins. Spectra were dominated by ions that represented protonated molecules, contained few other ions, and corresponded well with spectra acquired by other soft ionization techniques. Each biotoxin was successfully analyzed using similar ESI conditions. Nozzle-skimmer differential voltage greatly influenced spectra of several compounds by enhancing collision induced dissociation in the transport region of the ESI source. PMID- 8481413 TI - Determination of serum cholesterol by stable isotope dilution method using discharge-assisted thermospray liquid chromatography/mass spectrometry. AB - A discharge-assisted thermospray (plasmaspray) liquid chromatography/mass spectrometric method for the determination of total serum cholesterol is described. The method incorporates stable isotope dilution using (3,4 13C)cholesterol as an internal standard. Liquid chromatographic separation is performed using methanol as a flow solvent and effluents are directly introduced to the mass spectrometer. [MH-H2O]+ ions are monitored during liquid chromatography/mass spectrometry using the selected ion monitoring method. Satisfactory agreement between the analytical result and the certified value of the National Institute of Standards and Technology (formerly National Bureau of Standards) standard reference material serum is obtained with a relative standard deviation of 0.6%. PMID- 8481414 TI - Testing for prostate cancer. PMID- 8481415 TI - ESRD: pay now or pay later. PMID- 8481416 TI - Virginia's 'bold step' eases access for the uninsured. PMID- 8481417 TI - Medical center hour: breaking the bad news. PMID- 8481418 TI - 'Reform': practical solutions or political gain? PMID- 8481419 TI - Antitrust laws and the business of insurance. PMID- 8481420 TI - End stage kidney disease: increasing incidence in Virginia. AB - The incidence of new cases of end stage renal disease (ESRD) in Virginia increased an average of 14.5% annually from 1988 through 1991, producing a parallel increase in expenditures for the ESRD program. Hypertension (34%) and diabetes mellitus (32%) are the most frequent causes of ESRD in Virginia, with highest incidence among Afro-Americans and the elderly. Physicians should be aware of those at risk for ESRD so that reversible causes of renal failure can be identified and corrected. In addition, they should know which drugs to prescribe and which to avoid. Better detection and management of high blood pressure and diabetes mellitus can slow progressive renal failure and make a difference in the incidence of ESRD in Virginia during the coming years. PMID- 8481421 TI - Free radicals: only part of the story? PMID- 8481422 TI - Cerebral blood flow in patients with dementia of Alzheimer's type. AB - In the normal brain as well as in Alzheimer's disease (AD), regional cerebral blood flow (CBF) is coupled to metabolic demand and, therefore, changes in CBF reflect variations in neuronal metabolism. The use of radionuclide techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provides an accurate assessment of regional functional activity, i.e., CBF and metabolism, and could be very helpful for the differential diagnosis of AD. This disease is characterized by a decrease in global CBF and metabolism. When found, a symmetric bi-parieto-temporal CBF reduction is highly diagnostic for AD, despite the fact that a similar CBF pattern could also be observed in other types of dementia. Many AD patients with parieto-temporal flow reduction also have a diffuse flow reduction in the frontal cortical areas, particularly in advanced stages of the disease. Lateral CBF asymmetry is also very frequent; speech disorders are highly characteristic of left-sided flow reduction, while visuospatial apraxia is dominating in the right sided cases. In advanced and severe cases of AD, CBF and metabolism tend to be more uniformly reduced throughout the cortex, sparing only the primary visual and sensory-motor cortices. PET and SPECT measurement of brain perfusion and metabolism has added a new dimension to the knowledge of dementia disorders, with a better differential diagnosis between AD and other forms of dementia. The correlation with neuropsychological data has also given new insight into the disease. PMID- 8481423 TI - Established populations for epidemiologic studies of the elderly: study design and methodology. AB - A project initiated by the intramural Epidemiology, Demography and Biometry Program of the National Institute on Aging, entitled "Established Populations for Epidemiologic Studies of the Elderly" (EPESE), has developed information on death, chronic conditions, disabilities, and institutionalization for representative samples of elderly people living in communities. The EPESE consists of prospective epidemiologic studies of approximately 14,000 persons 65 years of age and older in four different communities: East Boston, Massachusetts; two rural counties in Iowa; New Haven, Connecticut; and segments of five counties in the north-central Piedmont area of North Carolina. The study design includes an initial baseline household interview followed by continued surveillance of morbidity and mortality. Participants are re-contacted annually in conjunction with the collection of data on cause of death and factors related to hospitalization and nursing home admissions. Concurrently, the investigators developed substudies focused on specific problems of the elderly. The value of this research lies in the longitudinal design which allows for analyses aimed at identifying risk factors of diseases, disabilities, hospitalizations, institutionalization, and mortality. PMID- 8481424 TI - Circadian secretion of melatonin and thyrotropin in hospitalized aged patients. AB - Alterations in periodical functions are known to occur in aging and may be regarded as markers of the aging process itself. Melatonin and Thyroid Stimulating Hormone (TSH) circadian periodicities were studied in 22 aged subjects and in 13 adult controls. The study of rhythmicity was performed by the Cosinor analysis. Elderly subjects were hospitalized because of various concomitant diseases. Circadian periodicity of both hormones was disrupted in the aged group, and the deterioration of melatonin periodicity was significantly correlated with the decay in cognitive functions, quantified by the Mini Mental State evaluation. Diabetes was also found to affect, though not significantly, melatonin, but not TSH, periodicity. Melatonin and TSH nocturnal peaks were decreased in aged people. TSH oscillation amplitudes were inversely correlated with age. No correlation was found between melatonin and TSH secretory features both in adult and in aged subjects. PMID- 8481425 TI - Body composition and its relation to bone mass and fractures in an urban and a rural population. AB - A higher incidence of fragility fractures in urban than in rural populations has been described. The present study included 954 randomly selected men and women between the ages of 40 to 80 years living in the cities of Malmo, an urban population, and Sjobo, a typical agricultural community. Lean body mass (LBM) was estimated with a bioelectrical impedance method; bone mineral content (BMC) of the forearm was evaluated by single photon absorptiometry, and strength of the quadriceps, and hamstring muscles of the right knee, and hand grip were measured. The age-related difference in LBM between the ages of 50 to 80 were 7.8 kg in men and 2.9 kg in women. Urban men aged 60 and 70, and women aged 50 and 70 had a 1.8 to 3.7 kg lower LBM than rural subjects. One hundred women (17%) and 28 men (11%) had experienced fragility fractures. Women aged 70 with fragility fractures had 3.1 kg lower LBM than women without fractures, and the age-dependent difference in LBM was greater in the urban and rural women with fracture, than in women without fracture. LBM showed a higher correlation to BMC, in the range of 0.20 0.28, than the correlation between body weight and BMC. Quadriceps muscle strength was lower in the elderly age groups in both sexes, and a 40% decline was seen both in those from the highest and lowest quartiles of LBM. Use of LBM instead of body weight showed higher correlations to flexion strength of the knee and hand grip.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481426 TI - Bone mineral density in relation to anthropometric properties, physical activity and smoking in 75-year-old men and women. AB - Bone mineral content (BMC, g.cm-2) and density (BMD, g.cm-3) were studied in 75 year-old men and women in relation to anthropometric and certain life-style factors. This study covered all the men and women born in 1914 who were residents in the city of Jyvaskyla in 1989 (N = 388). A hundred and three men and 188 women participated in bone measurements performed at the calcaneus using a 125I-photon absorption method. BMC was on average 36% and BMD 17% higher in the men than in the women. BMC and BMD associated with body mass in both sexes, and with body fat and use of estrogen in the women. There was a negative correlation between the BMD values and the number of cigarettes smoked over the entire life course in both sexes. Moderate physical activity was related to higher BMC in men. Men and women who had been physically active earlier in their life tended to show higher BMD values than those who had been more sedentary. PMID- 8481427 TI - Mutations of mitochondrial DNA support human aging. PMID- 8481428 TI - [Encrusted ulcerated lesion after a burn]. PMID- 8481429 TI - [Paramandibular mass in a diabetic woman]. PMID- 8481430 TI - [Acute, symmetrical polyarthritis as a manifestation of Staphylococcus aureus sepsis in a hemodialyzed patient]. PMID- 8481431 TI - [Clear-fluid meningitis in a patient with boutonneuse fever]. PMID- 8481432 TI - [Surgical wound infection and empyema caused by Pasteurella multocida]. PMID- 8481433 TI - [The toxic shock syndrome: apropos of a case]. PMID- 8481434 TI - [Alopecia and albendazole]. PMID- 8481435 TI - [Outbreak of familial botulism]. PMID- 8481436 TI - [Efficacy of cefsulodin -irgasan-novobiocin agar media in the isolation of Aeromonas mesophiles from feces]. PMID- 8481437 TI - [The Tween-80 test in the identification of Moraxella catarrhalis]. PMID- 8481438 TI - [Experimental model of Lyme disease in rats]. AB - BACKGROUND: An experimental model in rats can contribute to the understanding of the pathogenesis and improvement of treatment of Lyme borreliosis. OBJECTIVE: To develop a Lyme arthritis experimental model in Sprague-Davies rats. MATERIAL AND METHODS: An intraperitoneal inoculation of Borrelia burgdorferi in three groups of Sprague-Davies rats was made. The first group was inoculated with dead B. burgdorferi. The second group was inoculated with low virulence B-31 B. burgdorferi. The third group was inoculated with high virulence B-297 B. burgdorferi. RESULTS: After six months of follow-up, none of the rats in the first two groups presented arthritis whereas in the third group 18 rats (72%) developed arthritis in one or more joints. Histologic showed synovial hypertrophy and inflammatory infiltration composed of polymorphonuclear leukocytes, plasma and mast cells in the infected joint. B. burgdorferi was isolated in the liver and spleen cultures taken 14 days after inoculation in 40% of the rats inoculated with B-297 strain. CONCLUSION: An easy and inexpensive experimental model of Lyme arthritis in rats has been developed. PMID- 8481439 TI - [Perinatal Streptococcus agalactiae infections. Clinical epidemiological study and evaluation of a prevention program]. AB - BACKGROUND: To prove both the importance of SGB (group B streptococci) as a cause of perinatal infection and the efficacy of a prophylactic treatment in pregnant women with cervicovaginal colonization by SGB. METHODS: Retrospective study of 197 third trimester pregnant women who were carriers of SGB (155 received intrapartum prophylaxis) and of 44 patients with SGB infections during pregnancy, post-partum and neonatal periods. RESULTS: No neonatal sepsis was detected in the group of SGB carrier mothers who received antibiotic prophylaxis. In carrier pregnant women who did not receive prophylaxis, one case of neonatal sepsis by SGB was detected and a greater prevalence of intrapartum fever, and neonatal infection with negative cultures was observed. SGB was frequently isolated as a cause of early sepsis and neonatal meningitis (13 cases), intraamniotic infection (12 cases) and puerperal endometritis (8 cases). In 45% of the patients with perinatal infections by SGB, the cervicovaginal culture performed in the third trimester of pregnancy did not detect the presence of SGB. CONCLUSIONS: The administration of intrapartum ampicillin to pregnant SGB carriers permits the prevention of perinatal infections by this microorganism in a great number of patients, although the possibility of late colonization, which may not be detected during pregnancy, stil remains. PMID- 8481440 TI - [Application of PCR for the detection of mutations in the genes coding for beta lactamases]. AB - BACKGROUND: The purpose of this study was to develop a satisfactory technique to detect punctual mutations in blaTEM genes. METHODS: The strains [E. coli HB 101 pBR322 (TEM-1), E. coli J62 RP4 (TEM-2)] were submitted to PCR with primers PL1 and PL2 which amplify the genetic region susceptible of punctual mutations. Then, we developed Southern blot and hybridization with oligonucleotide probes (GIn 37, Lys 37 y Thr 261), corresponding to first and last mutations. RESULTS: A region of 841 bp was amplified using the primers previously described. Hybridization experiments with the Thr 261 probe gave positive signal with both strains (both carry the mutation); GIn 37 only hybridized with TEM-1 and Lys 37 only with TEM 2. CONCLUSIONS: The use of primers which amplify all the region susceptible of mutations in blaTEM and oligonucleotide probes allows the specific detection of point modifications in the original genes by the use of digoxigenin-labeled oligonucleotide probes. PMID- 8481441 TI - [Diagnosis of anaerobic infection of the pleural fluid using gas-liquid chromatography]. AB - BACKGROUND: An assessment of the efficacy of the detection of volatile and non volatile fatty acids that are produced by microorganisms aimed at the possible diagnosis of pleural empyema. METHODS: 106 pleural fluids were examined by gas liquid chromatography in contrast to conventional aerobic and anaerobic cultures. The sample previously prepared (1 microliter) was injected in an Hewlett-Packard 5890 chromatograph, that was equipped with a fused silica capillary column and a flame ionization detector. RESULTS: Growth of aerobic or anaerobic microorganisms was obtained in 13 (12.3%) of the samples, and volatile or non-volatile fatty acids were detected in all of them (sensitivity = 1). No growth was obtained in the 93 samples, but volatile or non-volatile fatty acids were detected in 64 (68.8%) of them (specificity = 0.31). A positive predictive value of 0.17 and a negative predictive value of 1 were obtained. Growth of anaerobic microorganisms was obtained in 9 samples (8.5%) and volatile fatty acids were detected in all of them (sensitivity = 1). Anaerobic microorganisms did not grow in 97 samples, however volatile fatty acids were detected in 2 (2.1%) of them. A positive predictive value of 0.82 and a negative of 1 were obtained. CONCLUSIONS: Referring to pleural fluid samples, the detection of volatile and non-volatile fatty acids by gas-liquid chromatography is a highly sensitive method, that may be used to quickly reject negative samples in about 30 mins. Furthermore, when anaerobic microorganisms exist, the high specificity of gas-liquid chromatography will make it possible to confirm their presence in the sample, mainly if there is a clinical suspect of anaerobic infection. Thus, the utilization of this sensitive method may also change the therapeutic behaviour. PMID- 8481442 TI - [Salmonella typhimurium as the causal agent of pulmonary cavitations]. AB - BACKGROUND: Relation between patients with immunosuppression (malignancy, renal transplant) and bacteremia by Salmonella non-typhi, specially by Salmonella typhimurium, is known. This relation has been published for patients who suffer from AIDS, and so Salmonella bacteremia could even begin the clinical disease. But even though the relation between the infection by Salmonella and AIDS is well known, and the pulmonary involvement in them has been told, this etiology as a producing agent of lung cavitation has not much documentation. METHODS: We examined three patients (two women and one man) suffering from fever of one week of duration, cough, expectoration and thoracic pain in two of them. The third patient had fever and cachexia without clinical symptoms. The man and the two women had a blood count with neutrophilia and leucocytosis in two cases and leucopenia in the other one. All of them suffered a very important depression of cell immunity (CD4 of 140, 70 and 4, respectively) and positive blood cultures for Salmonella typhimurium. RESULTS: Chest X-Ray showed, in all the cases, pulmonary cavities. CONCLUSIONS: Salmonella typhimurium must be included among the agents that can produce pulmonary cavities like Staphylococcus aureus, mycobacteria, fungus and other gram-negative bacilli. PMID- 8481443 TI - [Typing methods: plasmid analysis. Advantages and disadvantages]. PMID- 8481444 TI - Intermittent ischemia. PMID- 8481445 TI - Oxygenated crystalloid cardioplegia. PMID- 8481446 TI - Crystalloid versus blood cardioplegia. PMID- 8481447 TI - Technical considerations and logic of antegrade and retrograde blood cardioplegic delivery. PMID- 8481448 TI - Controlled aortic root reperfusion in cardiac surgery. PMID- 8481449 TI - Continuous normothermic blood cardioplegia. PMID- 8481450 TI - Myocardial protection in patients with acute myocardial infarction and cardiogenic shock. PMID- 8481451 TI - Myocardial protection for reoperative cardiac surgery in acquired heart disease. AB - We have reviewed a variety of techniques that have recently been used to improve the results of reoperation coronary bypass valve re-replacement and redo thoracic aortic surgery. The basic tenets of management in these high-risk areas are: (1) innovative use of cardiopulmonary bypass techniques to improve patient safety, including deep hypothermic arrest, (2) use of retrograde as well as antegrade infusion of cardioplegic solutions, (3) meticulous operative technique, (4) prevention of left ventricle distension, (5) TEE monitoring of intracardiac air, and (6) careful post-bypass hemodynamic monitoring. Reoperative CABG specifically requires avoiding injury to previously placed open conduits or atherosclerotic conduits, an increasingly recognized risk factor in these patients. Though direct myocardial cardioplegic protective techniques are very important for reducing operative risk, the importance of the total operative plan is critical for maximizing patient safety and ensuring improved long-term survival. PMID- 8481452 TI - Pediatric cardioplegic techniques. AB - We use warm induction and reperfusion with amino acid enhancement on all neonates and preoperatively stressed patients to induce arrest without contracture and to replete high-energy substrates. Blood cardioplegia is used in all age groups. We then employ hypothermia in the majority of patients (all neonates), ranging from deep (18 degrees C), to moderate (26 degrees to 28 degrees C), with warm or near normothermia used in only simpler anatomic repairs. The clear benefits of hypothermia in conferring additional cardiac and systemic ischemic protection along with the relatively greater ease of cooling and rewarming in the pediatric patient warrant its continued use in the majority of open-heart cases. Calcium levels are maintained in the 0.3 to 0.5 mM/L range during the conduct of the operation and reperfusion phase. Before removal from bypass, calcium is administered through either bolus or continuous drip technique to provide a normocalcemic level of 1 to 1.2 mM/L. This close attention is particularly important in the neonate to avoid contracture injuries and to maximize cardiac function, and is warranted if citrate-phosphate-dextrose (CPD)-containing transfusion or prime components are used. Preoperative evaluation for aortopulmonary collaterals with coil embolization is routinely performed, and is particularly important in single ventricle physiology where preserved myocardial function is so vital to a favorable outcome. The opportunity to perform some surgeries off bypass, such as on the RV outflow tract, may be used whenever it represents a viable alternative in very young or ill patients. Similarly, the majority of Glenn shunts, for example, are performed using a caval-RA shunt without formal cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481453 TI - Myocardial protection: an overview. PMID- 8481454 TI - Redefining nursing's role in Central Africa. Interview by Jim Lavery. PMID- 8481455 TI - Home care nursing in Ecuador. Interview by Karen Schmidt. PMID- 8481456 TI - A day in the life of a Dutch home care nurse. PMID- 8481457 TI - Out of the breast cancer closet. PMID- 8481459 TI - B.C. health care: the new vision. PMID- 8481458 TI - Camp nurse. PMID- 8481460 TI - Responding to anger. PMID- 8481461 TI - Let no one be silent. PMID- 8481462 TI - Cross border nursing. PMID- 8481463 TI - Role of protein synthesis, prostaglandins, and estrogen in rat ovarian metalloproteinase inhibitor production. AB - Matrix metalloproteinases and their inhibitors regulate follicular connective tissue remodeling associated with ovulation. We examined the control of metalloproteinase inhibitor activity and gene expression by various treatments in cultured rat granulosa cells and intact whole ovaries. Cells were isolated from preovulatory follicles of immature eCG-primed rats and cultured with various treatments for 24 h. Metalloproteinase inhibitor activity was measured in the media. The addition of LH or the phorbol ester 12-O-tetradecanoylphorbol 13 acetate (TPA) increased inhibitor activity 2.5- and 2.6-fold above that in control cultures, respectively. Cycloheximide treatment blocked basal and LH- and TPA-stimulated inhibitor activity, suggesting that the increase in granulosa cell inhibitor activity resulted from de novo protein synthesis. Indomethacin, a prostaglandin synthase inhibitor, had no effect on basal or LH-induced granulosa cell inhibitor activity. Addition of the antiestrogen tamoxifen citrate or an aromatase inhibitor, 10-propargylestr-4-ene-3,17-dione, did not affect basal or LH-stimulated inhibitor activity, implying that estrogen is not involved in the signal transduction pathway leading to increased inhibitor activity. Northern analysis demonstrated the presence of mRNA for a tissue-derived metalloproteinase inhibitor, TIMP-1, which increased with LH stimulation, in rat granulosa cells. Similarly, an hCG stimulus increased TIMP-1 mRNA in periovulatory ovaries to the highest levels prior to ovulation. Neither cycloheximide nor indomethacin altered hCG-stimulated TIMP mRNA levels in periovulatory ovaries. The present study demonstrates that the LH- and TPA-induced increase in inhibitor activity resulted from de novo protein synthesis; however, de novo protein synthesis does not appear necessary for the increase in TIMP mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481464 TI - Perforin-expressing cells during spontaneous abortion. AB - The metrial gland of pregnant rodents contains an abundant population of natural killer (NK)-like cells called granulated metrial gland (GMG) cells. Since GMG cells express the cytolytic protein, perforin, and since cells with NK activity have been implicated in spontaneous abortions, we have studied the distribution of perforin-containing cells in the uterus of mice undergoing normal pregnancy (Swiss mice) and spontaneous abortions (CBA/J x DBA/2 mice). The distribution of perforin-positive GMG cells was essentially the same near healthy and aborting conceptuses, suggesting that GMG cells are not involved in most cases of spontaneous abortion in this abortion model. Small perforin-positive cells were observed near the aborting conceptus in about 5% of the cases. However, it is not known whether their presence was the result or the cause of abortion. PMID- 8481465 TI - Comparative follicular development in Meishan and Large White gilts during prepubertal periods and its relation to hormonal stimulation. AB - Changes in follicular development in the left ovary and ovarian response to hormonal injections (hCG or eCG and hCG) in the right ovary were studied in Meishan gilts (n = 36) at 3, 2, and 1 standard deviations (SD) before the mean age of puberty (51, 64, and 77 days of age) and in Large White gilts (n = 24) at 3 and 1 SD (140 and 166 days of age). Left ovaries were removed at the time of hormonal treatments and the remaining ovaries were removed 18 h after hCG was injected alone (hCG) or 72 h after eCG was injected (eCG-hCG). Both nonatretic and atretic (> 4 pyknotic bodies) antral follicles > 0.6 mm in diameter were identified in the left ovaries by histological techniques. LH-sensitive follicles were identified in the right ovaries by counting follicles with dispersed cumulus cells around the oocytes. All large White gilts showed the presence of antral follicles at both 3 and 1 SD before puberty while 6, 7, and 12 Meishan gilts had antral follicles > 0.6 mm at 3, 2, and 1 SD before puberty, respectively. In Large White gilts, the mean number of nonatretic antral follicles > 0.6 mm remained constant at 3 and 1 SD before puberty, while in Meishan gilts, the mean number increased as gilts got older. Mean percentage of class 1 nonatretic follicles (0.6-1.12 mm) of the total number of nonatretic follicles increased significantly with age in Meishan gilts (p < 0.02), while those of class 3 (2.01 3.56 mm) decreased significantly (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481466 TI - Preparation of an enriched fraction of luteinizing hormone-secreting cells from a mixed population of rat anterior pituitary cells. AB - To determine whether female rat gonadotropes differentially secrete only LH, only FSH, or both LH and FSH, a new method of preparing an enriched fraction of LH secreting cells from a mixed population of cells was developed. Dispersed female rat pituitary cells were incubated for 4 h in glass tubes with magnetic beads coated with anti-LH antibody. The tubes were then placed in a magnetic particle concentrator to separate cells bound to antibody-coated beads (518b7-bound) from the rest of the cell population (518b7-unbound). Several controls were used in this experiment: 1) mixed cells immediately plated without any preincubation (control); 2) mixed cells incubated without magnetic beads (incubated-only); 3) mixed cells incubated with magnetic beads but not separated (nonseparated); and 4) mixed cells first incubated with magnetic beads coated with normal mouse serum (NMS) and then separated into NMS-bound and NMS-unbound populations. After removal of magnetic beads from cell populations, the cells were plated at 200,000 cells/well. The 518b7-bound cells secreted 1.5-, 2-, 2-, and 5-fold more LH than control, incubated-only, nonseparated, or 518b7-unbound cells, respectively (p < 0.05); 518b7-bound cells secreted 2.5-, 3.8-, 3.8-, and 11-fold more FSH than control, incubated-only, nonseparated, and 518b7-unbound cells. The ratio of LH:FSH secreted did not vary between the different treatment groups, but the ratio of LH:FSH contained in 518b7-selected cells was greater than that for unbound cells. Our data indicate that we have prepared an enriched fraction of LH secreting pituitary cells that also secrete FSH but have a greater capacity for producing LH than FSH in culture. These results are supportive of the view that LH and FSH are secreted by the same cells. PMID- 8481467 TI - Interference with the cytolytic activity of interleukin-2-treated lymphocytes by bovine uterine luminal protein. AB - Bovine uterine luminal protein (ULP) components (> or = 4 x 10(6) and 21,000 M(r)) were obtained from uterine flushings on Day 17 of pregnancy. Experiments were conducted to determine the capability of these components to interfere with the cytolytic activity of interleukin-2 (IL-2)-treated peripheral blood lymphocytes (PBL), designated LAK (lymphokine-activated killer) cells, upon K-562 tumor cells. Proteins (10-100 micrograms) were added at the onset of a 5-day culture period to wells containing PBL (3 x 10(6) + bovine recombinant IL-2 (12,000 IU). After culture, percentage cytotoxicity (Cyt) was assessed by the 51Cr release assay at 4 and 22 h of incubation for ratios (5:1-200:1) of LAK:K 562 cells. Percentage Cyt was affected (p < 0.0001) by time, ratio, protein treatment, and all two-way interactions. Although trends were apparent, neither ULP component affected (p > 0.05) percentage Cyt at 4 h. By 22 h of incubation, mean percentage Cyt values for the > or = 4 x 10(6) and 21,000 M(r) components at effector:target cell ratios of 150:1 (p < 0.002) and 200:1 (p < 0.0001) were less than percentages for LAK cells alone. BSA and serum protein (control preparations) each failed (p > 0.05) to affect percentage Cyt. In conclusion, both ULP components interfered with the cytolytic activity of LAK cells, presumably by the suppression of LAK cell generation. PMID- 8481468 TI - Modulation of preimplantation embryonic development by antisense oligonucleotides to major histocompatibility complex genes. AB - The Ped (preimplantation embryo development) gene, which controls the rate of mouse preimplantation embryonic cleavage division and subsequent survival of the embryo, maps to the Q region of the MHC (major histocompatibility complex). Mouse embryos were treated with antisense oligonucleotides to mRNA for the Q region genes Q7/Q9, each of which encodes the Qa-2 antigen. The reverse transcription polymerase chain reaction (RT-PCR) was used to show that antisense treatment, but not sense treatment, decreased the level of mRNA for Qa-2 antigen in preimplantation embryos. Furthermore, both the expression of Qa-2 protein and the rate of embryonic cleavage division were decreased by treatment with antisense but not sense oligonucleotides. These results provide direct evidence that the Ped gene phenotype is at least partially encoded by the Q7/Q9 genes. It is likely that the mouse Ped gene has a human homolog, perhaps within HLA-F. Identification of genes--such as the Ped gene--that affect survival of the embryo may be vitally important for the enhancement of animal and human reproductive success. PMID- 8481469 TI - Localization of a spermatid-specific histone 2B protein in mouse spermiogenic cells. AB - Mammalian spermiogenesis is characterized by chromatin condensation and replacement of the histones typical of somatic and earlier spermatogenic cells by protamines in the nucleus. However, a spermatid-specific H2b histone (ssH2b) that has an unusual carboxyl-terminus containing a region rich in hydrophobic amino acids is transcribed and translated in mouse round spermatids. The hydrophobicity of this region suggested that the protein may be localized at the nuclear envelope, the initial site of chromatin condensation during spermiogenesis. To identify ssH2b in the spermatid nucleus, an antiserum (anti-ss-H2b127-138) was generated against a synthetic peptide corresponding to the unique carboxyl terminus of the protein. Immunocytochemistry of fixed, frozen testicular sections at both the light and electron microscopic levels indicated that ssH2b is present in nuclei of round spermatids. Moreover, the protein was not found to be preferentially associated with the nuclear envelope, indicating that it is not involved in chromatin-nuclear envelope interaction in the round spermatid. Rather, it appeared to be distributed uniformly throughout the nucleus with the exception of its exclusion from the nucleolus. In addition, the ssH2b protein was not found in mature sperm even when the chromatin was partially decondensed, suggesting that it is present and functions only during a restricted period of spermatogenic development. PMID- 8481470 TI - Alteration of growth, advancement of puberty, and season-appropriate circannual breeding during 28 months of photoperiod reversal in woodchucks (Marmota monax). AB - In woodchucks (Marmota monax), as in other marmotine rodents, endogenous circannual metabolic and reproductive cycles persist and free-run at intervals of 10-12 mo for up to 4 yr in a neutral photoperiod of 12L:12D. The annual metabolic cycle is not altered by exposure to constant long days or short days for several months. In the wild, changes in food intake cause body weight to peak in late summer and reach nadirs in early spring, and there is a single annual breeding season in late winter. To determine whether normal changes in photoperiod entrain the endogenous circannual cycle, aspects of reproduction, food intake, and body weight were studied for 28 mo in eight groups of woodchucks housed in light controlled rooms. These included four groups of 7-10 males and four groups of 7 10 females exposed to automated and continuous daily changes in photoperiod. The imposed changes in photoperiod resembled native Northern Hemisphere (boreal) changes or Southern Hemisphere (austral) changes in photoperiod. The treatments started at the summer solstice shortly after capture as 2.5-mo-old juveniles or 14.5-mo-old yearling adults. In austral vs. boreal woodchucks, started as juveniles, annual increases in testosterone and testis descent at 5, 14, and 23 mo of study were advanced by 2, 5, and 6 mo, respectively. Annual increases in progesterone at 7, 16, and 25 mo of study were advanced by 4, 5, and 6 mo, respectively. The older woodchucks were significantly but less dramatically affected by austral photoperiod for the first 6 mo of study, and by 8-12 mo were advanced the same as the younger animals. At 16-17 and 26-27 mo of photoperiod reversal, 16 austral females had normal pregnancy rates (78%) and produced normal sized litters (4.3 +/- 0.2) that were advanced by 5 and 6 mo, respectively, relative to those of boreal controls. Body weights in austral vs. boreal juveniles were reduced at 3-5 mo of study but not in older woodchucks. At 1 and then 2 yr of austral lighting, peaks in body weight were advanced by 4 and then 5 mo relative to boreal controls in young animals, and by 2 and then 5 mo in older animals. Between 1 and 2 yr of austral lighting in both age groups the nadirs in food intake (45 g per day) were about 16-25% of peak food intake 6-8 mo earlier, as in boreals, but advanced by 5-6 mo relative to boreals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481471 TI - Presence of transforming growth factor-alpha messenger ribonucleic acid (mRNA) and absence of epidermal growth factor mRNA in rat ovarian granulosa cells, and the effects of these factors on steroidogenesis in vitro. AB - Granulosa cell steroidogenesis has been reported to be modulated by transforming growth factor-alpha (TGF alpha) and its biochemical and physiological analog, epidermal growth factor (EGF). In this report, we studied whether TGF alpha or EGF mRNA is produced by granulosa cells, examined the morphological effects of TGF alpha or EGF on granulosa cell cultures, and measured the changes in granulosa cell progesterone production in cells cultured with TGF alpha or EGF. RNA from fresh granulosa cells and from those incubated overnight and for 4, 7, and 10 days with FSH was studied with reverse transcription-polymerase chain reaction for TGF alpha and for EGF. Only TGF alpha mRNA appeared to be present in the granulosa cells. Phase-contrast microscopy revealed that the combination of FSH plus TGF alpha or EGF resulted in cell shape changes and an increase in lipid droplets in the granulosa cells. Electron microscopy revealed that the endoplasmic reticulum increased in the granulosa cells incubated with either EGF or FSH plus EGF. Mitochondria of granulosa cells incubated with growth factors possessed ultrastructural features consistent with those found in preovulatory granulosa cells. Culture of the granulosa cells with FSH plus TGF alpha or with FSH plus EGF resulted in significantly elevated progesterone and 20 alpha hydroxyprogesterone levels. The highest level of progesterone production was on the eighth day of culture. We conclude that TGF alpha mRNA is produced by granulosa cells and that granulosa cell differentiation, as defined by morphological and biochemical criteria, is significantly stimulated in vitro by the combination of FSH and TGF alpha. PMID- 8481472 TI - Expression of H-2K major histocompatibility antigens on preimplantation mouse embryos. AB - Genes in the major histocompatibility complex (MHC) have been shown to play a role in development and reproduction. In the mouse, class I MHC proteins are expressed on oocytes and preimplantation embryos. Each mouse strain contains multiple class I genes located in the classical regions, K and D, and the nonclassical regions, Q and TL, of the mouse MHC, the H-2 complex. This study was undertaken to evaluate the expression of the classical class I MHC antigen, H-2K, on preimplantation mouse embryos. Through use of appropriate monoclonal antibodies (mAb) and an ELISA procedure, it was shown that H-2K antigens are detectable on oocytes and blastocyst-stage embryos, but not on 2-cell or 8-cell embryos. This pattern of expression is different from that reported in previous studies showing expression of total class I antigens and the nonclassical MHC antigen, Qa-2, on all stages of preimplantation embryos, including 2-cell- and 8 cell-stage embryos. To analyze the nature of the H-2K protein on blastocysts, H 2K antigens were isolated from an H-2K overproducing cell line (RDM-4) and used in blocking experiments. It was found that the purified antigen blocked binding to tissue culture cells by 54% and to embryos by 68%. Therefore, H-2K antigens on tissue culture cells and embryos appear to be very similar, but perhaps not identical. Thus escape of embryos from surveillance by the maternal immune system may not be effected by the expression of a different or embryonic form of MHC antigens. PMID- 8481473 TI - Induction by estradiol-17 beta of polycystic ovaries in the guinea pig. AB - In the present study we wished to develop a model for polycystic ovarian syndrome (PCOS) using the guinea pig, because this animal's cycle, compared to other rodent models, more closely emulates that of humans. Four silastic capsules, either empty or containing cholesterol or estradiol-17 beta, were placed subcutaneously for 48 h on Day 10 or 12 of the cycle. Vaginal smears were taken daily. Cardiac blood was drawn at various intervals. At necropsy, trunk blood was collected and ovaries were excised and analyzed histologically. Cycle length was extended over that in controls in animals treated with estradiol-17 beta (E2) on Day 12 of the cycle. Treatment with E2 resulted in an increase in serum estrogen 2 h after capsule insertion. No changes were evident in progesterone or androstenedione concentrations with treatment. Animals treated with E2 and killed late (54 days after capsule removal) showed cysts grossly (group A), while occult cysts were present in E2-treated animals killed early (17 days; group B); no cysts were observed in control groups. Ovarian weight and size were increased in group A over controls. There was an increase in the fraction of atretic:total follicles < 500 mm in size in group A compared to group B as well as compared to controls. Since these results are similar to those seen in human PCOS, we conclude that the guinea pig may serve as an exceptional and unique model for the study of PCOS and may be applicable to humans. PMID- 8481474 TI - Follicular development and ovulation in the marmoset monkey as determined by repeated laparoscopic examination. AB - This paper describes the course of follicular development in vivo in the marmoset monkey, the only anthropoid primate with a relatively high (2-4) and variable ovulation number. Results are presented in relation to predictions from a mathematical model of control of follicle selection and ovulation number. Repeated laparoscopic examinations during the follicular phase were conducted for 14 cycles. Ovulatory follicles were 1.0 mm (median) in diameter at Day 6 and could be distinguished from nonovulatory follicles by Day 8, at which point they were 2.0 mm in diameter. Ovulations were not synchronous; the most common observation 1-2 days after the estradiol peak was ovulation of one follicle but not the other. Examination of the course of follicular development within a cycle and the distribution of ovulation sites both supported predictions stemming from a mathematical model of follicle selection developed by Lacker et al. [Biol Reprod 1987; 37:570-580]. Specific findings were the following: 1) Variations in patterns of follicle growth within a cycle resembled those generated by the model; in 64% of cycles, the 2-3 ovulatory follicles grew at similar rates. However, in 36% of cycles, ovulatory follicles displayed disparate rates of growth. 2) An examination of the distribution of ovulation sites (right versus left) revealed no significant difference from a binomial distribution, suggesting the likelihood that interovarian (rather than intraovarian) factors control this distribution. PMID- 8481475 TI - Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. AB - Repair of human endometrium after menstruation and preparation of the endometrium for implantation involves profound angiogenic changes. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. Four species of mRNA encoding VEGFs were identified in human endometrium and myometrium. All species were present throughout the menstrual cycle. Two species, VEGF165 and VEGF121, were present in peripheral leukocytes, indicating tissue-specific splicing of the two other VEGF transcripts. In situ hybridization of mRNA encoding VEGF was not restricted to vascular smooth muscle but was present in epithelial and stromal cells of endometrium throughout the cycle, and the distribution changed during the course of the cycle. All four species of VEGF were expressed by the endometrial carcinoma cell lines Ishikawa, HEC 1-A, and HEC 1-B. Estradiol increased steady state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1 A cells. Conditioned medium from these cells possessed angiogenic activity that was depleted by passage through a heparin affinity column. None of the cell lines demonstrated mRNA for acidic or basic fibroblast growth factor (FGF), despite previous reports of the identification of immunoreactive basic FGF in HEC 1-A and HEC 1-B cells. These findings show that VEGFs, not FGFs, are the principal angiogenic growth factors secreted by these cells and that human endometrium expresses a secreted angiogenic growth factor whose site of expression changes during the menstrual cycle. PMID- 8481476 TI - Temporary anestrus induced by injection of luteinizing hormone-releasing hormone in hamsters. AB - The photoperiod-induced anovulatory state of the Syrian hamster (Mesocricetus auratus) is characterized by a daily rhythm of circulating LH and FSH with a surge in blood levels occurring each afternoon. The association between anestrus and the presence of daily gonadotropin surges suggests that initiation of the characteristic daily rhythm of LH and/or FSH after transfer to short days results in blockade of ovulation. We tested whether daily injection of LHRH affects the 4 day rhythm of vaginal estrous cycles, induces daily surges of LH and FSH, blocks ovulation, and induces regression of the ovaries. LHRH (1 microgram/animal) was injected (s.c.) at 1630 h each day into females with regular 4-day estrous cycles. Injections began on the afternoon of estrus and continued for 12 days (experiment 1) or 8 days (experiments 2 and 3). In saline-injected controls, vaginal discharges occurred regularly at 4-day intervals during the injection period in all experiments. In contrast, vaginal estrus was not observed during the period of LHRH injection in any animals. Ova were found in oviducts of all saline-injected controls (8.9 +/- 0.8; n = 8) on the morning of estrus (after 8 injections), but no ova were found in oviducts of LHRH-injected females. Levels of plasma LH but not FSH increased after injection of LHRH each day, whereas the 4-day estrous cycle rhythm of gonadotropins was not disturbed in saline-injected controls. Vaginal estrous cycles and a 4-day rhythm of LH release resumed within 7 days after LHRH injections were stopped.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481477 TI - Effect of recombinant bovine somatotropin on the superovulatory response to pregnant mare serum gonadotropin in heifers. AB - Treatment of mature heifers with recombinant bovine somatotropin (BST) increases the number of ovarian follicles of 2-5 mm in diameter. This study was carried out to investigate whether the increase in the number of small follicles induced by BST treatment can enhance the superovulatory response. In the first experiment, 24 heifers were assigned, in a randomized block design, to four treatment groups: 1) control; 2) BST; 3) pregnant mare serum gonadotropin (PMSG); 4) BST+PMSG. On Day 7 of the estrous cycle, animals in groups 2 and 4 received injections of 320 mg BST (in a sustained release formulation), while heifers in groups 1 and 3 received 10 ml saline. Five days later heifers in groups 3 and 4 were treated with a single dose of 2000 IU PMSG to induce superovulation. Embryos were recovered nonsurgically on Days 6-8 of the following cycle, and all heifers underwent laparoscopy on Day 9 to assess ovulation rate. In a second experiment, 24 heifers were assigned randomly to four treatment groups: 1) PMSG (1000 IU); 2) BST (320 mg) + PMSG (1000 IU); 3) PMSG (2000 IU); 4) BST (320 mg) + PMSG (2000 IU), and then treated as for experiment I. In both experiments, all heifers were scanned daily using real-time ultrasound from the day before BST injection until the day of ovulation to monitor dynamics of ovarian follicular growth and development, and blood samples were collected daily throughout the experimental period for measurement of peripheral progesterone, estradiol-17 beta, growth hormone (GH), and insulin-like growth factor-I (IGF-I).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481478 TI - Gelatinolytic and caseinolytic proteinase activities in the secretions of the ventral, lateral, and dorsal lobes of the rat prostate. AB - The ventral, lateral, and dorsal lobes of the rat prostate produce secretions rich in protein. We examined these secretions for proteinase activities, using gelatin- and casein-containing SDS-polyacrylamide gel zymographies. The ventral lobe demonstrated both higher activities and more molecular forms of proteinase activities that cleaved these two protein substrates than did the other lobes. Ca(2+)-stimulated gelatinolytic activities of approximately 48, 51, 58, 64, 74, and 80 kDa were found in ventral prostate secretions in addition to activities detected in the absence of added Ca2+: a very strong 27-kDa activity; prominent 22-, 86-, 90-, and 94-kDa activities; and less active 36-, 41-, 100-, 130-, and 140-kDa activities. Ca(2+)-stimulated gelatinolytic activities of 51, 58, 74, 80, 86, 90, and 94 kDa were present in lateral prostate secretions (none were detected in secretions of the dorsal lobe), and Ca(2+)-independent activities of 25, 27, and 100 kDa were found in secretions of both the lateral and dorsal lobes. The Ca(2+)-stimulated activities were inhibited by EGTA and EDTA. Benzamidine inhibited all gelatinolytic activities except for the 22-, 25-, and 27-kDa Ca(2+)-independent forms when Ca2+ was not added to the reaction buffer. However, in the presence of 5 mM CaCl2, the Ca(2+)-stimulated forms of proteinase were unaffected by benzamidine, whereas the other activities sensitive to benzamidine were inhibited. Prominent Ca(2+)-independent caseinolytic activities of 20, 23, 31, 37, 83, 89, and 94 kDa were detected in ventral lobe secretions along with less active forms of about 39, 48, 53, 57, 60, 63, 80, 103, 110, 125, and 160 kDa. Caseinolytic activities of approximately 23, 31, 53, 89, 94, 103, 120, and 125 kDa were found in lateral prostate secretions, and 89, 94, and 103 kDa activities were found in secretions of the dorsal lobe. Quantitatively, most gelatinolytic and caseinolytic activities were present in the soluble portion of the secretion of each prostatic lobe. The ventral, lateral, and dorsal prostate lobes all secrete gelatinolytic and caseinolytic proteinase activities; however, quantitatively the ventral lobe is the most notable in this function since its secretions contain more molecular forms and greater activities of these proteinases. PMID- 8481479 TI - Regulation of messenger ribonucleic acid encoding 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in the ovine corpus luteum. AB - Three experiments were conducted to determine how steady-state levels of mRNA encoding 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD) in the ovine corpus luteum vary 1) between the two steroidogenic luteal cell types, 2) during the estrous cycle, and 3) during prostaglandin F2 alpha (PGF2 alpha)-induced luteolysis. In the first experiment, RNA (10 micrograms) was isolated from purified preparations (n = 4) of large or small steroidogenic luteal cells. Large luteal cells contained 42% more (p < 0.05) message for 3 beta HSD per microgram RNA than did small luteal cells, while the amount of mRNA for tubulin did not differ between the two types of luteal cells. To determine whether luteal levels of mRNA for 3 beta-HSD differ during the estrous cycle, corpora lutea were collected from cycling ewes (n = 3/day) on Days 3, 6, 9, 12, and 15 postestrus. Levels of mRNA for 3 beta-HSD were similar on Days 3, 6, 9, and 12 but were lower (p < 0.05) on Day 15 postestrus, while levels of mRNA for tubulin were unchanged. In the final experiment, ewes were treated on Day 10 postestrus with two injections of PGF2 alpha (5 mg each) or saline (control) at a 4-h interval. Corpora lutea were collected from ewes (n = 4/treatment) 1 h or 8 h after the second injection of PGF2 alpha or 8 h after the second saline injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481480 TI - Effect of neonatal diethylstilbestrol exposure on volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus and pituitary responsiveness to gonadotropin-releasing hormone in female rats of known anogenital distance at birth. AB - The effects of neonatal diethylstilbestrol (DES) exposure on the volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN-POA) and on GnRH-stimulated LH secretion were investigated in castrated female rats of known anogenital distance (AGD) at birth. The AGD was measured in females on the day of birth, and 0.1 microgram DES or corn oil was injected from Days 1 through 10 of life. The volume of the SDN-POA was significantly larger in animals that had received DES than in those that had received corn oil. The largest SDN-POA volumes were seen in DES-treated animals that had long (> 1.4 mm) AGDs, and smallest volumes in corn oil-treated females that had short (< or = to 1.4 mm) AGDs. Within treatment groups, animals with longer AGDs had significantly larger SDN-POA volumes than those with short AGDs. Within AGD subgroups, the effect of DES was similar in that the percentage increase in SDN-POA volume was equivalent. Pituitary responsiveness to GnRH was greater in corn oil-treated females with long AGD than in similarly treated females with short AGD. DES treatment blunted LH secretion in both AGD subgroups, but the increased LH secretion was preserved in rats with long AGD. The results indicate that the individual effects of the postnatal environment depend on the androgenicity of the intrauterine microenvironment. Further, variations in the individual's response to potential environmental hazards may be predicted by antecedent intrauterine events. PMID- 8481481 TI - Testicular weight, Sertoli cell number, daily sperm production, and sperm output of sexually mature rabbits after neonatal or prepubertal hemicastration. AB - The present study was conducted to investigate the influence of hemicastration and age at hemicastration on the subsequent testicular development of male rabbits through sexual maturity. Thirty New Zealand white rabbits were left intact or were hemicastrated on Day 35, 49, 77, or 105 postconception. Beginning at 7 mo of age, ejaculates were collected every other day for 1 mo, and the last ten ejaculates were used to quantify daily sperm output. At 8 mo, the rabbits were killed and their carcases, testes, testicular capsules, and epididymides were weighed. Testicular tissue was processed for quantification of sperm production rates by enumeration of homogenization-resistant spermatids and via histometric evaluation. Regardless of the age at hemicastration, this manipulation did not alter the development of the remaining testis as assessed from testis weight, numbers of Sertoli cells per testis, daily sperm production, or sperm output (p > 0.05). On the basis of these findings, it would appear that the development of the spermatogenic capacity of the remaining testis of the rabbit is not altered appreciably by hemicastration at a young age. PMID- 8481482 TI - Birth of mice after transplantation of early cell-cycle-stage embryonic nuclei into enucleated oocytes. AB - The present study was conducted to investigate the influence of cell cycle stage of the donor nucleus on chromatin structure and development of mouse embryonic nuclei transplanted into enucleated oocytes. Donor cell-cycle stage was controlled in order to examine, in addition, the developmental potential of nuclei from 2-, 4-, and 8-cell-stage embryos. The cell cycle stage of donor nuclei was classified as early, middle, or late. After nuclear transfer, electrofusion, and activation, early-stage transplants formed a single pronucleus like structure, but middle-stage transplants formed very irregular types of structures and late-stage transplants extruded a polar body. A high proportion of development to the blastocyst stage (77.8%) and an increased cell number (62.1 cells) were obtained from the early 2-cell-stage transplants as opposed to the middle- (0%) and late-stage (20.8%, 37.0 cells) transplants (p < 0.001). With transplantation of early-stage nuclei, high proportions of development to the blastocyst stage and of offspring were obtained from nuclear transplant embryos with a nucleus from a 2-, 4-, or 8-cell-stage embryo. The results confirm that the donor cell-cycle stage critically affects the chromatin structure and development of nuclear transplant embryos. The results also demonstrate that the nuclei from 2-, 4-, and 8-cell-stage mouse embryos in the early stage of each cell cycle can be reprogrammed when transplanted into enucleated mature oocytes. PMID- 8481483 TI - Suckling-induced inhibition of luteinizing hormone secretion and follicular development in the early postpartum sow. AB - The endocrine basis of lactational anestrus, the causes of reproductive dysfunction after early weaning, and the relationships among LH, FSH, and prolactin (PRL) secretion and follicular development were evaluated in sows weaned 6 h after farrowing (zero-weaned, n = 8) and in normally lactating sows (n = 9). An irregular, high-frequency episodic-type pattern of LH secretion was present in the early postpartum period, irrespective of treatment, and in a proportion of sows this pattern was associated with a marked elevation of baseline LH concentrations. This pattern of LH secretion was maintained in the zero-weaned sows but LH secretion was inhibited in lactating sows, resulting in a difference (p < 0.05) in mean plasma LH between groups 72-78 h postpartum. There were no differences in FSH between groups in any period of sampling. Variable but elevated plasma PRL was observed in suckled sows but declined (p < 0.05) to basal levels within 12 h of zero-weaning. Follicular development measured at laparotomy or slaughter 96 h postpartum was greater (p < 0.05) in zero-weaned than in control sows. The development of lactational anestrus in the sow therefore requires suckling-induced inhibition of LH secretion by 78 h postpartum. This inhibition of LH release does not appear to be causally related to short-term changes in PRL secretion. PMID- 8481484 TI - Luteinizing hormone and prolactin responses to naloxone vary with stage of lactation in the sow. AB - The principal aim of this study was to investigate the involvement of an opioidergic mechanism in the development of suckling-induced inhibition of LH secretion during early lactation in the sow. A preliminary experiment suggested that 2 mg/kg naloxone given as a single bolus injection was above the threshold for antagonism of endogenous opioid activity in early lactation. In the main experiment, injection of 2 mg/kg naloxone 39 h postpartum, followed by injection of 1 mg/kg naloxone at 3-h intervals from 42 h to 78 h postpartum, was not able to prevent the gradual inhibition of LH secretion observed in untreated lactating sows. In contrast, a single injection of 2 mg/kg naloxone at Day 10 of lactation was effective in increasing LH secretion (p < 0.05). There were no effects of the naloxone treatment at any time on FSH secretion. Naloxone decreased (p < 0.05) plasma prolactin at Day 10 of lactation; but again during the first 78 h after farrowing, chronic naloxone treatment did not affect plasma prolactin. These data suggest that the development of the inhibitory effect of suckling on LH secretion in the sow may not be opioid dependent. In contrast, an opiate-dependent mechanism was confirmed as an important component of the suckling-induced suppression of LH secretion in established lactation. PMID- 8481485 TI - Differential genomic imprinting of major histocompatibility complex class I antigens in the placenta of the rat. AB - The RT1.A and Pa (class I) loci in the major histocompatibility complex (MHC) of the rat are genomically imprinted in the placenta, since only the paternally derived antigens are expressed. To determine whether the RT1.E (class I) locus, which defines the end of the MHC opposite RT1.A, is genomically imprinted in the placenta, two different types of crosses were studied: all possible mating combinations of the DA (AaE-) and WF (AuEu) inbred strains and various matings of the R16 (AaE-), R33 (AaEu), and R34 (AaE-) congenic recombinant strains. The results showed that the Eu locus was not imprinted. Thus, genomic imprinting can be different at two endogenous loci that are part of a multigene family in tight linkage disequilibrium. The lack of Eu imprinting is not due to the locus' being monomorphic, since the monomorphic Pa locus is imprinted, and it is most probably not due to its distance from the imprinted RT1.A and Pa loci (0.4 cM). We suggest that the control of the imprinting may lie in the physical structure of the DNA proximate to the imprinted locus. PMID- 8481486 TI - A method for reactivation of the movement of demembranated ram sperm models with decondensed nuclei and a description of their ultrastructure. AB - In the procedure described, demembranated ram sperm models were treated to decondense their nuclei, and the movement of their sperm tails was then reactivated. The duration of movement was sustained for more than 30 min, with a tail-wave frequency of up to 14 Hz. Decondensed sperm models adhered to each other and to the slide; but adherence was prevented by addition of an anti agglutination factor derived from dialyzed, freeze-dried ram seminal plasma, which allowed models to swim freely. Electron microscopy showed that most areas of the sperm model nuclei were decondensed and contained fine interconnected filaments with structures resembling nucleosomes at anastomosing regions. Some central, lateral, and basal regions of the nuclei were not fully decondensed. The axoneme, outer dense fibers, and fibrous sheath were not affected ultrastructurally by the extraction procedure; the mitochondria of the middle piece appeared to be extracted, while the acrosome but not the perforatorium was removed. Use of decondensed, reactivated sperm models provides a means to monitor the decondensation of sperm in vitro while maintaining minimal disruption to sperm tail components. This will allow access to the nucleus for experimental manipulation in sperm models. PMID- 8481487 TI - Porcine uterine retinol-binding proteins are identical gene products to the serum retinol-binding protein. AB - Retinol-binding proteins (RBP) are secreted by the porcine uterus under the influence of progesterone and consist of multiple charge forms. Evidence has been previously presented by this laboratory that these uterine RBP are distinct from serum RBP. We have followed the secretion of the uterine RBP during two stages of pseudopregnancy, examined their properties and amino acid sequences, and attempted to clone their cDNA. Analysis of the charge forms present in uterine flushes by anion-exchange chromatography showed that forms 1 (p < 0.01) and 3 (p < 0.05) predominated at Day 13, whereas forms 2 (p < 0.05) and 4 (p < 0.01) were most abundant at Day 45. All four charge forms appeared to form stable complexes with transthyretin (TTR) and were recognized by antiserum to human serum RBP on Western blots. Several cDNA clones isolated from an endometrial cDNA library all appeared to code for a protein identical to classical RBP. Off-blot amino acid sequencing of the first ten residues of two of the more divergent charge forms of uterine RBP indicated complete sequence identity with pig serum RBP. These data suggest that the uterine RBP charge forms may be slightly modified forms of a single protein product corresponding to the classical form of RBP. The change in appearance of the charge forms during pseudopregnancy is probably due to chemical modifications. These modifications do not appear to influence the binding of each charge form to TTR. PMID- 8481488 TI - Risk factors for renal cell carcinoma: results of a population-based case-control study. AB - For a case-control study of risk factors for renal cell carcinoma, a mailed questionnaire was used to collect data on 518 cases and 1,381 population-based controls in Ontario, Canada. Active cigarette smoking increased risk twofold among males (odds ratio estimate [OR] = 2.0, 95 percent confidence interval (CI) = 1.4-2.8) and females (OR = 1.9, CI = 1.3-2.6). Passive smoking appeared to increase risk somewhat among nonsmokers (males: OR = 1.6, CI = 0.5-4.7; females: OR = 1.7, CI = 0.8-3.4). A high Quetelet index (QI) was associated with a twofold increase in risk in both sexes, although this was based on reported weight at age 25 years for males (OR = 1.9, CI = 1.2-3.1) and five years prior to data collection for females (OR = 2.5, CI = 1.4-4.6). Diuretic use was associated with significantly increased risk among females, but not among males. Phenacetin use increased risk, while acetaminophen use was not associated with altered risk, although few subjects used either compound. Multiple urinary tract infections increased risk, but only significantly in females (OR = 1.9, CI = 1.2-2.9). Our data indicate the need for further exploration of passive smoking and diuretics as risk factors, as well as elucidation of mechanisms by which high lifetime QI and frequent urinary-tract infections might increase risk of this cancer. PMID- 8481489 TI - Nasopharynx cancer in Italian migrants. AB - Incidence and mortality for nasopharynx cancer in Italian migrants to Australia, Brazil (Sao Paulo), Canada, England and Wales, France, Uruguay, and the United States (Connecticut; Los Angeles and San Francisco, California) are analyzed. While the available incidence and mortality rates in the south of Italy--from where a large majority of migrants derive--are comparable to or lower than the other Western countries, the study shows a high risk in Italian migrants compared with the locally-born populations. These results are consistent in both sexes and in all host countries with the exception of the two South American ones. This finding possibly reflects a migration from some Italian sub-areas at higher risk, consistent with the high risk reported for some other Mediterranean populations (Maghreb, Malta). PMID- 8481490 TI - Serum lipids and left-sided adenomas of the large bowel: an extended study of self-defense officials in Japan. AB - In the on-going study of men retiring from the Self-Defense Forces in Japan, we previously reported that serum total cholesterol was not related to colorectal adenomas but that men with low levels of serum high-density lipoprotein (HDL) cholesterol had an elevated adenoma risk. We examined whether the previous observation was reproducible in a different set of data accrued subsequently in the study. Serum total cholesterol, HDL-cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were compared between 138 cases of colorectal adenomas at the depth of 60 cm or less from the anus and 909 controls with normal sigmoidoscopy in the period from October 1988 to December 1990. There was virtually no relation between adenoma risk and any of the serum lipids studied with or without adjustment for smoking, alcohol use, and body mass index. In the analysis combining the earlier and present data, however, men with large adenomas (> or = 10 mm, n = 25) tended to have lower levels of total cholesterol and LDL-cholesterol compared with controls (n = 1,612); adjusted mean differences were -0.21 mmol/l (P = 0.24) and -0.26 mmol/l (P = 0.13), respectively. These findings are inconclusive, but hypocholesterolemia may be associated with the growth of colorectal adenoma. PMID- 8481491 TI - Tobacco, alcohol intake, and diet in relation to adenocarcinoma of the esophagus and gastric cardia. AB - Little is known about the etiology of adenocarcinoma of the distal esophagus/cardia, a cancer which has increased in incidence in the United States over the last two decades. We analyzed data on smoking, alcohol use, dietary intake, and other factors obtained from 173 hospitalized males with adenocarcinoma of the distal esophagus/cardia (cases) and 4,544 hospitalized males with diseases not related to smoking and of other organ systems than the gastrointestinal tract (controls). Cases of squamous cell carcinoma of the esophagus (n = 136) and adenocarcinoma of the distal stomach (n = 122) were included as separate case groups. All subjects were interviewed in 28 hospitals in eight cities in the US between 1981 and 1990. After adjustment for covariates, the odds ratio (OR) for adenocarcinoma of the distal esophagus/cardia for current smokers was 2.3 (95 percent confidence interval [CI] = 1.4-3.9) and that for ex smokers was 1.9 (CI = 1.2-3.0) relative to never-smokers. The OR for drinkers of four or more ounces of whiskey-equivalents of alcohol per day (relative to those consuming less than one drink per week) was 2.3 (CI = 1.3-4.3). Intakes of total fat and vitamin A from animal sources were significant risk factors and fiber intake was associated inversely with adenocarcinoma of the distal esophagus/cardia. Although the number of female cases of adenocarcinoma of the distal esophagus/cardia was small (n = 21), significant associations were observed for smoking and alcohol. PMID- 8481492 TI - Migration to towns, occupation, smoking, and lung cancer: experience from the Finnish-Norwegian lung cancer study. AB - A total of 4,604 men who were interviewed in Finland in 1962 in connection with the Finnish-Norwegian lung-cancer study were followed-up for lung cancer during 1963-87 to establish why urbanized (via migration) men who smoked had a greater lung-cancer risk than native urban smokers. Exposure to occupational carcinogens was inferred from the title of the longest job held. A clear dose-response relation between occupational exposure and lung cancer was found in the urbanized but not among the native urban dwellers. The extra risk associated with migration to towns and smoking was found especially by those urbanized subjects who worked in heavily exposed industries: their lung cancer risk was more than twice that of native urban men in similar jobs, while those urbanized subjects in academic or clerical jobs showed no increased risk when compared with native urban men in corresponding work. Cardiorespiratory symptoms had a prognostic value in every residential group, but especially among the urbanized. Urbanized men who smoked and worked in heavily exposed industries, and suffered from shortness of breath, had a fourfold risk of lung cancer when compared with native urban smokers without this symptom. We conclude that although the joint effect of smoking and occupational exposure is the main explanatory factor for high risk of lung cancer in urbanized males, environmental and psychosocial factors also may have a contributory effect. PMID- 8481493 TI - Pesticide exposures and multiple myeloma in Iowa men. AB - A population-based case-control study of 173 White men with multiple myeloma (MM) and 650 controls was conducted in Iowa (United States), an area with a large farming population, to evaluate the association between MM, agricultural risk factors, and exposure to individual pesticides. A slight nonsignificantly elevated risk for MM was seen among farmers (odds ratio [OR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.7). Although slight excesses were observed, there were no significant associations between MM and handling either classes of pesticides or specific pesticides. Thus, this study found little evidence to suggest an association between risk of MM and farming or pesticides. PMID- 8481494 TI - Are the known bladder cancer risk-factors associated with more advanced bladder cancer? AB - Risk factors for superficial and invasive bladder cancer were examined in a case control study of 470 cases identified in 1967-68 in the Brockton and Boston Standard Metropolitan Areas (MA, United States) and of 500 population-based controls. Histologic specimens were reviewed and classified as superficial or invasive, following a standardized protocol. The tobacco-associated risk for superficial bladder cancer was odds ratio (OR) = 2.6 (95 percent confidence interval [CI] = 1.7-4.1) and the risk for invasive bladder cancer was OR = 1.7 (CI = 1.1-2.5). For subjects less than 60 years of age, the risks were greater for invasive tumors (OR = 4.3, CI = 1.2-15) than for superficial tumors (OR = 2.0, CI = 0.9-4.2), but this pattern for tobacco use was not found in older subjects. A strong trend of increased risk with increased amount of cigarettes smoked was shown only for invasive bladder tumors. No clear pattern of excess risk for invasive bladder tumors was seen for age at first use and years since last use of tobacco. The risk associated with occupational exposure to aromatic amine bladder carcinogens was OR = 1.7 (CI = 0.8-3.3) for superficial and OR = 1.5 (CI = 0.8-3.0) for invasive bladder cancer. For subjects less than 60 years of age, the risks were greater for invasive (OR = 12.0, CI = 2.1-65) than for superficial tumors (OR = 4.3, CI = 0.8-24), but this pattern for occupational exposure was not found in older subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481495 TI - Risk factors for small intestine cancer. AB - Small intestine cancer is relatively rare. Clinical reports have suggested that several medical conditions may predispose to increased occurrence of this cancer, but otherwise its etiology is unknown. In one of the first case-control studies of this cancer, we compared questionnaire responses provided by next-of-kin of 430 persons who died of small intestine cancer cf921 controls who died of other causes. Subjects were identified from decedents included in the 1986 United States National Mortality Followback Survey. The questionnaires sought information on demographic and lifestyle characteristics, including diet and use of tobacco and alcohol. Tobacco and alcohol consumption were unrelated to risk of small intestine cancer, but weekly or more frequent consumption of red meat and monthly or more frequent intake of salt-cured/smoked foods were associated with two- to three fold increases in risk. The findings suggest that dietary factors probably are involved in risk of small intestine cancer, but additional research in other settings is required to clarify the determinants of these rare cancers. PMID- 8481496 TI - Accuracy of death certificates in East Germany. PMID- 8481497 TI - Epidemiology of the M-component immunoglobulin types of multiple myeloma. AB - The purpose of this population-based case-control study was to learn whether risk factors differ for the individual immunoglobulin types of multiple myeloma. In particular, we sought to determine whether IgA and IgG myeloma were related to a history of exposure to reported IgA- and IgG-stimulating conditions, respectively, or to a history of selected occupational and physicochemical exposures. The M-component immunoglobulin type was determined from immunoelectrophoresis as reported in medical records, and exposure status was obtained through in-person interviews. IgG (56 percent) and IgA (22 percent) M components predominated. For 17 percent of cases, no peak was found on immunoelectrophoresis; they were presumed to have light-chain myeloma. Persons with these three types of myeloma did not differ with respect to distributions of age or race, but a somewhat higher proportion of light-chain cases were women (58 percent cf 45 percent of all other cases). Detailed analysis of the IgA and IgG subtypes provided little evidence that they differ with respect to prior immune stimulation or employment in several specific jobs. IgA myeloma, but not IgG myeloma, was associated modestly with a history of exposure to chest and dental X rays. Our study provides little evidence that IgA and IgG myeloma differ with respect to the risk factors examined. PMID- 8481498 TI - Recent cohort trends in malignant melanoma by anatomic site in the United States. AB - The incidence of malignant melanoma has been increasing steadily in the United States. The increase may be due to lifestyle changes in subsequent generations or birth cohorts. The nine population-based tumor registries in the Surveillance, Epidemiology, and End Results program (SEER) have been in existence for a sufficient time to begin to investigate cohort trends for the US population. Cases were the 18,787 Caucasians aged 20 to 84 years, who reported to SEER registries with a diagnosis of melanoma in 1974-86. Among men born between 1890 and 1919, each subsequent five-year birth cohort experienced 45 to 57 percent increases in age-adjusted melanoma incidence of the arm and trunk, and 14 to 20 percent increases were experienced across each site (arm, leg, head, and trunk) for the 1920-44 cohorts of men. Among women born between 1890 and 1919, 24 to 29 percent increases were seen for melanoma of the trunk, arms, and legs for each subsequent five-year birth-cohort, followed by six to 29 percent increases in the 1920-44 cohorts. Recent birth cohorts, 1945-64, have shown stabilizing rates, even after an attempt to adjust for the increasing tendency for diagnoses to be made in doctors' offices. Thus, the dramatic birth-cohort effects appear to have ended beginning with those born in 1945. However, melanoma rates will continue to rise until those born after 1945 represent the majority of the population. Furthermore, for the most recent cohorts, the trunk has become the most common site (per square meter of body surface) for men and the second most common site for women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481499 TI - The relationship of stressful life events, health status and stress-resistance resources in persons with AIDS. AB - Depression and hopelessness are major problems in persons with AIDS (PWAs). This study provides a paradigm for viewing these mental health states as outcomes that are dependent on stressors, physical health states, and stress-resistance resources. The sample consisted of 30 male, English-speaking PWAs with stage IV AIDS. A significant positive relationship was found between negative life events and the measure of depression, and number of complications and depression. Satisfaction with social support, intrapersonal hope, and global hope were all significantly, negatively associated with hopelessness. The findings support the importance of stress-resistance resources in promoting mental health in PWAs. PMID- 8481500 TI - The administration of didanosine (ddI) in the adult: a nursing perspective. AB - Until October 1991, zidovudine was the only licensed anti-HIV drug. Because zidovudine has limitations, the development of additional drugs is needed. One such drug is didanosine, which received FDA approval for patients who are intolerant of zidovudine or who have received prolonged zidovudine therapy. The authors provide an overview of the administration and adverse effects of didanosine, and recommend nursing interventions. PMID- 8481501 TI - Standards and evaluation in community-based case management. PMID- 8481502 TI - Connecting and disconnecting: bereavement experiences of six gay men. AB - This research investigation explored the bereavement experiences of gay partners of men who died of AIDS-related complications. Interviews with six men provided data for analysis using the qualitative method of grounded theory. Two basic social-psychological processes were identified that characterized the bereavement experience: connecting and disconnecting. Themes generated from the data that described the process of connecting were: sharing the death, caring for the PWA, legitimizing the relationship, memorializing, and AIDS-related work. Performing death-related tasks, letting go of the relationship, and passage characterized the process of disconnecting. Special considerations for bereavement in gay men and implications for nursing are discussed. PMID- 8481503 TI - Disseminating research: writing abstracts. AB - Disseminating research findings is a critical step in making research useful. Careful preparation of abstracts allows investigators the opportunity to communicate their findings effectively to other healthcare professionals. This paper presents criteria developed by the Association of Nurses in AIDS Care (ANAC) Research Committee to be used in reviewing research abstracts for future ANAC conferences. Content of abstracts and ideas for abstract development are provided, along with a brief analysis of the reviews of research abstracts submitted for the 1992 ANAC Annual Conference. PMID- 8481504 TI - AIDS-designated units or scatter beds: which is better? PMID- 8481505 TI - Structure, function, and activation of the erythropoietin receptor. PMID- 8481506 TI - Current status of cytogenetic research in childhood acute lymphoblastic leukemia. PMID- 8481507 TI - Elevated interleukin-8 serum concentrations in beta-thalassemia and graft-versus host disease. AB - Neutrophil chemotactic and functional defects occur in beta-thalassemia and in patients after bone marrow transplantation (BMT). Interleukin-8 (IL-8) is a novel chemotactic and activating peptide for neutrophils and can be detected in the circulation. IL-8 serum concentrations were evaluated in 30 beta-thalassemic patients before and after BMT. Serial samples from 16 patients were also studied. Fourteen sera from healthy children, 43 patients with chronic viral hepatitis, 16 patients on chronic transfusion treatment for various hematologic disorders, and 28 healthy adults were studied as controls. IL-8 was evaluated by an enzyme linked immunosorbent assay. Patients with beta-thalassemia had higher IL-8 concentrations than did normal controls, patients with liver disease, and patients on chronic transfusion. beta-Thalassemic patients with severe liver siderosis and fibrosis had the highest IL-8 concentrations. After BMT in patients with successful engraftment, IL-8 concentrations decreased significantly. In contrast, in patients with acute graft-versus-host disease (GVHD), IL-8 concentrations were not statistically different from the concentrations found before BMT and were higher than in patients with no complications and patients with graft rejection. IL-8 may play a part in the immune dysregulation that occurs in beta-thalassemia and may be involved in the immune mechanisms leading to GVHD. PMID- 8481508 TI - Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor chimeric transgenes for terminal differentiation coupled to growth arrest and apoptosis. AB - Conditional mutants of the myeloblastic leukemic M1 cell line, expressing the chimeric mycer transgene, have been established. It is shown that M1 mycer cells, like M1, undergo terminal differentiation coupled to growth arrest and programmed cell death (apoptosis) after treatment with the physiologic differentiation inducer interleukin-6. However, when beta-estradiol is included in the culture medium, M1 mycer cells respond to differentiation inducers like M1 myc cell lines, where the differentiation program is blocked at an intermediate stage. By manipulating the function of the mycer transgene product, it is shown that there is a 10-hour window during myeloid differentiation, from 30 to 40 hours after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, where activation of c-myc has no apparent effect on mature macrophages. M1 mycer cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal myelopoiesis and in leukemogenesis, also providing a strategy to clone c-myc target genes. PMID- 8481509 TI - Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma. AB - Anti-B-blocked ricin (anti-B4-bR) combines the specificity of the anti-B4 (CD19) monoclonal antibody with the protein toxin "blocked ricin." In blocked ricin, affinity ligands are attached to the ricin B-chain to attenuate its lectin binding capacity. In a phase I trial, Anti-B4-bR was administered by 7-day continuous infusion to 12 patients in complete remission after autologous bone marrow transplantation (ABMT) for relapsed B-cell non-Hodgkin's lymphoma (NHL). Patients were treated at 20, 40, and 50 micrograms/kg/d for 7 days. Potentially therapeutic serum levels could be sustained for 3 to 4 days. The maximum tolerated dose was 40 micrograms/kg/d for 7 days (total 280 micrograms/kg). The dose-limiting toxicities were reversible grade IV thrombocytopenia and elevation of hepatic transaminases. Mild capillary leak syndrome was manifested by hypoalbuminemia, peripheral edema (4 patients), and dyspnea (1 patient). Anti immunotoxin antibodies developed in 7 patients. Eleven patients remain in complete remission between 13 and 26 months post-ABMT (median 17 months). These results show that Anti-B4-bR can be administered with tolerable, reversible toxicities to patients with B-cell NHL in complete remission following ABMT. PMID- 8481510 TI - Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation. AB - The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with multifactor-responsive HPP-CFC, renews in vivo granulopoiesis in a manner comparable with marrow harvests without 5-FU pretreatment, and provides accelerated in vivo platelet recovery. This marrow may be an appropriate target marrow for gene insertion in gene-therapy protocols. PMID- 8481511 TI - Phenotypic and functional characterization of competitive long-term repopulating hematopoietic stem cells enriched from 5-fluorouracil-treated murine marrow. AB - Lymphomyeloid stem cells from the bone marrow of C57BL/6 mice treated with 5 fluorouracil (5-FU) were characterized with respect to 12 parameters using fluorescence-activated cell sorting and a competitive long-term repopulation assay. Stem cells were larger than lymphocytes and exhibited side light-scatter characteristic of blast cells. Most expressed low levels of Thy-1.2, high levels of Sca-1 (Ly6-A/E), H-2Kb, and AA4.1 antigens and stained brightly with rhodamine 123. Significantly, most long-term repopulating cells also expressed CD4, some at high density. In addition, a significant proportion displayed low to medium levels of the "lineage-specific" markers CD45R (B220), Gr-1, and TER-119. A simple and rapid multiparameter sorting procedure enriched the stem cells 100 fold and substantially removed most other clonogenic cell types, including day 12 spleen colony-forming cells. Cells able to generate cobblestone colonies on stromal cells in vitro were co-enriched. Lethally irradiated mice transplanted with limiting numbers of the sorted stem cells did not survive unless cotransplanted with "compromised" marrow cells prepared by prior serial transplantation and shown to be depleted of long-term repopulating activity. A significant number of recipients transplanted with 25 to 100 sorted cells contained donor-derived B and T lymphocytes and granulocytes in their peripheral blood for at least 6 months. Limiting dilution analysis in vivo indicated that the frequency of competitive long-term repopulating units (CRU) in the sorted population was at least 1 in 60 cells. The calculated frequency of CRU was largely independent of the time of recipient analysis between 10 and 52 weeks, indicating that highly enriched stem cells can be recruited relatively early in certain transplant settings. This simple enrichment and assay strategy for repopulating hematopoietic stem cells should facilitate further analysis of their regulation in vivo. PMID- 8481512 TI - Echicetin: a snake venom protein that inhibits binding of von Willebrand factor and alboaggregins to platelet glycoprotein Ib. AB - Echicetin, a new protein isolated from Echis carinatus venom by reverse phase and ion exchange chromatography specifically inhibited agglutination of fixed platelets induced by several platelet glycoprotein Ib (GPIb) agonists, such as bovine von Willebrand factor (vWF), alboaggregins, and human vWF in the presence of botrocetin. Unlike alboaggregins, echicetin bound to GPIb but did not induce agglutination of washed or fixed platelets. In contrast to disintegrins, it did not block adenosine 5'-diphosphate (ADP)-induced platelet aggregation in the presence of fibrinogen. The apparent molecular weight of echicetin measured on sodium dodecyl sulfate (SDS) gel electrophoresis was 26 Kd under nonreducing conditions. On reduction, echicetin showed 16 and 14-Kd subunits suggesting that the molecule is a dimer. Reduced echicetin retained its binding activity and its inhibitory effect on the agglutination of fixed platelets induced by bovine vWF. 125I-echicetin bound to fixed platelets with high affinity (kd = 30 +/- 1.8 nmol/L) at 45,000 +/- 2,400 binding sites per platelet. The binding was selectively inhibited by a monoclonal antibody to the 45-Kd N-terminal domain of platelet GPIb, but not by monoclonal antibodies to other regions on GPIb. Binding of 125I-bovine vWF to fixed platelets was strongly inhibited by echicetin. In contrast, bovine vWF showed a much weaker inhibitory activity on binding of 125I echicetin to platelets. The half life of echicetin in blood was approximately 170 minutes with no detectable degradation. Echicetin significantly prolonged the bleeding time of mice, suggesting that it may inhibit vWF binding to GPIb in vivo as well as in vitro. PMID- 8481513 TI - Vanadate activates platelets by enhancing arachidonic acid release. AB - Human platelet activation is associated with, and regulated by, the phosphorylation of a number of proteins. Recently, attention has been focused on tyrosine phosphorylation of proteins and their function in platelet activation. Here vanadate, an inhibitor of tyrosine phosphohydrolase, was used to examine the role that tyrosine phosphorylation plays in platelet activation. Vanadate (7.5 to 100 mumol/L) stimulated the dose-dependent aggregation of saponin-permeabilized, but not intact, platelets. Electron-microscopic studies indicated small degranulated aggregates. Vanadate-induced aggregation was inhibited by pretreatment with prostacyclin (1 to 10 nmol/L), genistein (1 to 10 micrograms/mL), aspirin (100 mumol/L), or BW755C (80 mumol/L). Aggregation was associated with the aspirin-sensitive formation of [32P]phosphatidic acid and the phosphorylation of platelet proteins, notably pleckstrin and myosin light chain. Immunoblotting studies indicated that vanadate caused the tyrosine phosphorylation of proteins of approximate molecular weights 26, 29, 32, 40, 42, 80, and 90 Kd. Preincubation with BW755C abolished the phosphorylation of the 26 , 29-, 32-, 40-, and 42-Kd proteins but not the 80- and 90-Kd proteins. Vanadate stimulated the release of [3H]-arachidonic acid that was not affected by pretreatment with BW755C. The subsequent conversion of [3H]-arachidonic acid to [3H]-thromboxane A2 was significantly inhibited. These findings show that vanadate stimulates platelets by promoting arachidonic acid release from phospholipids. Tyrosine phosphorylation, potentially of the 80- or 90-Kd proteins, may regulate a platelet phospholipase A2. The release arachidonic acid was converted to thromboxane A2 that produced secondary effects such as phospholipase C activation, protein phosphorylation, and aggregation, and was associated with the tyrosine phosphorylation of the 26-, 29-, 32-, 40-, and 42-Kd proteins. PMID- 8481514 TI - Double heterozygosity for mutations in the platelet glycoprotein IX gene in three siblings with Bernard-Soulier syndrome. AB - Bernard-Soulier syndrome (BSS) giant platelets have defective and/or deficient glycoprotein (GP) Ib/IX complexes, causing absent ristocetin-induced aggregation, defective interaction with von Willebrand factor, morphologic abnormality, and a clinical bleeding tendency. Recently several mutations have been described in the platelet GPIb alpha gene in individuals exhibiting the BSS phenotype. We have studied a family with classical BSS, and have excluded lesions at the GPIb alpha locus by restriction fragment length polymorphism linkage analysis. Analysis of the genes for two other components of the platelet GPIb:IX complex, namely GPIb beta and GPIX, showed two different missense mutations in the coding region of the GPIX gene: an A-->G transition in codon 21 results in conversion of an aspartic acid to glycine and an A-->G change in codon 45 converts an asparagine residue to serine. Three affected individuals are doubly heterozygous for these mutations, which alter conserved residues in or flanking the GPIX leucine-rich glycoprotein motif. Both mutations create new recognition sites for the enzyme Fnu 4H1; therefore, this enzyme was used to screen 60 normal subjects (120 alleles). Neither mutation was detected in any subject other than direct relatives of the affected individuals. Although low levels of GPIb were demonstrable by both flow cytometry and immunoblot analysis in an affected individual's platelets, there was no evidence of GPIX immunoreactivity. We propose that expression of abnormal GPIX prevents stable assembly of the GPIb/IX complex, causing BSS in the doubly heterozygous individuals in this family. PMID- 8481515 TI - Spreading of platelets on fibrin is mediated by the amino terminus of the beta chain including peptide beta 15-42. AB - We have investigated the adhesion and spreading of platelets on polymerized fibrin of varying structure to identify sites that mediate these interactions. Fibrin was prepared with thrombin to remove both fibrinopeptide A (FPA) and fibrinopeptide B (FPB) and with reptilase or Agkistrodon contortrix thrombin-like enzyme (ACTE) to selectively remove FPA or FPB, respectively. Residual fibrin bound enzymes were inhibited with D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK). Platelet adhesion was independent of fibrinopeptide cleavage and was equal on fibrin prepared with each of the three enzymes. In contrast, FPB cleavage increased spreading as quantitated by fluorescence microscopy of platelets stained for glycoprotein IIb-IIIa. The 24% +/- 4% spreading on reptilase-fibrin was significantly less than the 70% +/- 8% on thrombin-fibrin or 65% +/- 9% on ACTE-fibrin (P < .0005 for both). Protease III from Crotalus atrox venom was used to specifically cleave residues B beta 1-42 from fibrinogen to further investigate the role of the beta chain N-terminus in promoting platelet spreading. After clotting with thrombin, this fibrin derivative lacked beta 15-42 and supported significantly less spreading. A monoclonal antibody (MoAb) reactive with beta 15-21 inhibited spreading on thrombin-fibrin as did peptide beta 15-42, while control MoAbs and peptides had no significant effect. These results indicate that adhesion and spreading of platelets on fibrin are mediated by different interactions, and that spreading can be mediated by FPB cleavage and the amino terminus of the beta chain including residues beta 15-42. PMID- 8481516 TI - Deficiency of plasma plasminogen activator inhibitor 1 results in hyperfibrinolytic bleeding. AB - A 63-year-old man was evaluated for a lifelong history of bleeding commencing with frequent epistaxis as a child; all previous routine coagulation parameters were within the normal range. The patient's hemorrhagic disorder is characterized predominantly by delayed bleeding at surgical sites. In the resting state, there was no clinical or laboratory evidence of excessive fibrin(ogen)olysis. Bleeding was not caused by disseminated intravascular coagulation, factor XIII deficiency, alpha 2-antiplasmin deficiency, or dysfibrinogenemia. It was found that the patient was deficient in plasma PAI-1 antigen and activity but with approximately half normal antigen and normal activity of platelet PAI-1. The low concentration of plasma PAI-1 was insufficient to neutralize circulating t-PA, resulting in high t-PA activity with normal antigen and causing the hyperfibrinolytic activity observed. Studies on seven family members of the proband indicated autosomal inheritance of plasma PAI-1 deficiency. Studies on this patient emphasize a clear correlation between decreased plasma PAI-1 activity and hyperfibrinolytic bleeding and also emphasize the unique role of plasma PAI-1 in the balance between the coagulation and fibrinolytic mechanisms. PMID- 8481517 TI - Role of leuCAM integrins and complement in platelet-monocyte rosette formation induced by immune complexes of human immunodeficiency virus-type 1-immune thrombocytopenic purpura patients. AB - Patients with human immunodeficiency virus-type 1-immune thrombocytopenic purpura (HIV-1-ITP) have elevated polyethylene glycol (PEG)-precipitable immune complexes (ICs) composed of IgG, IgM, and complement that are threefold to sevenfold higher than in healthy control subjects. These complexes contain anti-F (ab')2 as well as anti-idiotype antibodies versus anti-HIV-1gp120. Because anti-F (ab')2 and anti-idiotype antibodies correlate with thrombocytopenia (r = .83 [J Clin Invest 77:1756, 1986] and r = .90 [J Clin Invest 89:356, 1992], respectively) we studied the binding of ICs to platelets and monocytes as well as their role in platelet monocyte rosette formation. ICs bind to platelets in a saturation-dependent manner (optimum at 10 micrograms/mL; 0.5% of serum conc). Binding to platelets could not be inhibited with platelet saturating concentrations of aggregated IgG or with monoclonal antibody (MoAb) IV.3 versus FcR gamma II. Platelet binding could be inhibited with Fab anti-C3, anti-Clq, or anti-C4 by 57%, 40%, and 46% respectively, not with control Fab (P < .001). Monocytes from HIV-1-ITP patients form rosettes with normal platelets 16.8 +/- 5.2 rosettes/100 monocytes compared with 4.8 +/- 0.8 control monocytes plus normal platelets (P = .009). Gel-washed HIV-1-ITP platelets formed 19 +/- 2.0 rosettes with U937 cells compared to 6.3 +/ 1.0 for normal platelets (P = 0.001). Arming of U937 cells with HIV-1-ITP ICs (5 micrograms/mL) formed 36.7 +/- 2.5 rosettes compared with 10.6 +/- 1.2 for control ICs (P < .01). Rosetting of armed U937 cells could be inhibited with MoAbs versus the alpha chains of CD11a (LFA-1), 11b (Mac-1), or 11c (p150,95) by 67%, 70%, and 61%, respectively (P < .007), whereas binding of ICs to U937 cells was unaffected. Isotype-matched control as well as MoAbs versus antigens on U937 cells (CD13, CD33) or the anti-FcR gamma II receptor had no effect. However, Fab fragments of polyclonal anti-C3 inhibited rosette formation by 78% (P < .01); control Fab had no effect. Thus, platelet-monocyte rosette formation is not Fc dependent. It is complement receptor dependent and requires the cooperation of all three leuCAM integrins. PMID- 8481518 TI - Phenotypic diversity of natural killer (NK) populations in patients with NK-type lymphoproliferative disease of granular lymphocytes. AB - Using monoclonal antibodies (MoAbs) termed GL183 and EB6, directed to a novel family of natural killer (NK) specific triggering molecules, four functional subsets of NK cells have been recently defined (GL183+EB6-; GL183+EB6+; GL183 EB6+; GL183-EB6-). In healthy individuals, all these subsets are represented in variable portion. The expression of EB6 and GL183 surface antigens has been analyzed in a series of 14 patients with lymphoproliferative disease of granular lymphocytes (LDGL) characterized by a chronic CD3-CD16+ lymphocytosis. Our data showed that in 11 of 14 cases, the proliferation was specifically sustained by one of the four possible subsets of granular lymphocytes (GLs) (seven cases: EB6 GL183-; three cases: EB6+GL183-; one case: EB6-GL183+). In the remaining three cases, a pattern was demonstrated that is consistent with that of healthy individuals (ie, the presence of all four subsets). When expressed on GL surfaces, in the majority of cases tested both EB6 and GL183 MoAbs behave as functional surface molecules as assessed in the redirected killing of P815 target cells. We also provided evidence that EB6+GL183+ proliferating cells show a definite (type 1) in vitro NK specificity as do their normal counterparts. The unique expansion of a defined subset of NK cells in most patients with LDGL suggests that the pathologic noxa leading to GL proliferation selectively acts on a specific subset of NK lymphocytes. PMID- 8481519 TI - Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. AB - Acute lymphoblastic leukemia (ALL) in infants generally shows distinctive biologic features and has a poor prognosis. Cytogenetic studies indicate that many infant leukemias have chromosome 11q23 translocations. Because of these findings and the distinct clinical features of infant leukemia, we investigated 30 cases of infant ALL for molecular defects of 11q23. Fourteen cases had cytogenetic abnormalities of 11q23, and all of them showed 11q23 rearrangements at the molecular level. An additional seven cases also had 11q23 molecular rearrangements, including one with normal cytogenetic analysis. Molecular abnormalities of 11q23 were significantly correlated with adverse prognostic factors, including age under 6 months, hyperleukocytosis, CD10- phenotype, and early treatment failure. Molecular analysis identified a group of infants with germline 11q23 that had a very good treatment outcome with a projected event-free survival of 80% at median follow-up of 46 months compared to 15% in infants with rearranged 11q23 (P < .001). These findings suggest that a high proportion (70%) of infants with ALL have 11q23 rearrangements and that these rearrangements are not always detectable by cytogenetic analysis. The presence of germline 11q23 DNA may identify a subgroup of infant ALL patients with a good outcome using current therapy and a different etiology for their ALL. PMID- 8481520 TI - Granulocyte-macrophage colony-stimulating factor induces sequential activation and deactivation of binding via a low-affinity IgG Fc receptor, hFc gamma RII, on human eosinophils. AB - Eosinophils are important in antibody-mediated immune defense against parasites based on interaction with Ig receptors (FcR). Of the three classes of IgG FcR in humans, hFc gamma RI, II, and III, solely hFc gamma RII (CD32) is expressed on freshly isolated eosinophils. Despite an expression level similar to that found on monocytes and polymorphonuclear granulocytes, binding activity of hFc gamma RII on eosinophils is constitutively low. Freshly isolated eosinophils had a negligible ability to form rosettes with IgG-sensitized erythrocytes (EA-IgG). Addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) caused an approximately threefold increase in EA-IgG rosettes. This increase was maximal after 35 minutes, and declined upon further incubation at 37 degrees C. Analysis of hFc gamma RII expression levels showed no significant changes and neither was the expression of other hFc gamma R classes induced. Blocking studies with anti Fc gamma receptor monoclonal antibody (MoAb) proved hFc gamma RII specificity of enhanced IgG complex binding. These phenomena were not restricted to GM-CSF action, because the addition of interleukin-3 or interleukin-5 similarly enhanced EA-IgG binding. The kinetics of activation of hFc gamma RII binding activity were paralleled by the binding of EA-C3bi to CR3 on eosinophils. In contrast to the stable expression of hFc gamma RII during activation with GM-CSF, CR3 expression increased slowly. Ligand binding via both types of opsonin receptors proved receptor specific. However, the kinetics of enhanced binding via hFc gamma RII and CR3 suggested the possibility of a common mechanism underlying the enhancement of ligand binding via hFc gamma RII and CR3. This hypothesis was supported by the fact that binding via hFc gamma RII proved sensitive to both high concentrations of F(ab')2 fragments of anti-CD11b MoAb MO1 and chelation of bivalent cations with EDTA. In conclusion, our studies indicate that cytokines can induce a transient enhancement of hFc gamma RII binding activity. Qualitative, and not quantitative, changes in this receptor appear to underly the modulation of binding activity, which may be linked to changes in CR3 activity. PMID- 8481521 TI - Kinetics of hemoglobin S polymerization and gelation under shear: I. Shape of the viscosity progress curve and dependence of delay time and reaction rate on shear rate and temperature. AB - Polymerization and gelation of deoxyhemoglobin S makes red blood cells (RBCs) rigid and is the immediate basis of pathogenesis in sickle cell disease. Hence, characterization of hemoglobin S viscosity and its time-dependent development as RBCs pass through the microvasculature is important in understanding pathogenesis. Because RBCs and the intraerythrocytic milieu in vivo are subject to shear, the shear dependence of polymerization kinetics is also important. In steady-state cone-plate viscometry we find: (1) gelation under shear progresses exponentially with time; (2) shear markedly increases exponential rate and (3) shortens delay time independent of when in the delay time it is applied; (4) shear greatly decreases the temperature dependence of the exponential rate and delay time; (5) simultaneous with its acceleratory effect on polymerization, shear breaks down gel structure. We conclude that shear acts to accelerate gelation by breaking fibers and creating new growing ends, a process that occurs in addition to the homogeneous and heterogeneous nucleation of new fibers that occurs in the absence of shear. Fibers that break are part of a gel network rather than in free solution. The shear dependence of gelation rates means that the critical clinical issue, whether the delay time is long enough and gelation slow enough to permit deoxygenated cells to pass through the microvasculature before they rigidify, depends on in vivo shear rates as well as on degree of unsaturation and hemoglobin concentration. PMID- 8481522 TI - Sickle erythrocyte-endothelial interactions in microcirculation: the role of von Willebrand factor and implications for vasoocclusion. AB - To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes. PMID- 8481523 TI - Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a single amino acid substitution (426 Arg-->Gln) associated with hereditary hemolytic anemia. AB - A point mutation (1277 CGG to CAG) was identified in the R-type pyruvate kinase (PK) cDNA of a PK variant, PK Sapporo, associated with hereditary non-spherocytic hemolytic anemia. The mutation causes a single amino acid substitution from Arg to Gln at the 426th amino acid residue of human R-type PK; consequently, the hydrophobicity around the mutated site is drastically decreased. The amino acid change occurred in the eighth alpha helix of A domain (A alpha 8) of PK, and it has been proposed that this region as well as A alpha 7, A beta 7, and A beta 8 is a potassium (K+) binding site. Because K+ binding to the PK subunit is considered to be essential for substrate binding, the mutation might account for the decreased affinity for phosphoenolpyruvate (PEP). This is compatible with the fact that all the reported PK variants carrying point mutations in those area have a high Michaelis constant (Km) for PEP. PMID- 8481524 TI - Origin of a soluble truncated transferrin receptor. AB - It has recently become evident that elevation of reticulocytes in the circulation of several species, including humans, leads to the formation of a noncellular transferrin receptor (TFR). In humans, the majority of the released receptor is in truncated form (Shih et al: J Biol Chem 265:19077, 1990). In other species (sheep, rat, chicken) the receptor is associated with a vesicle (exosome) and is full length (Johnstone et al: J Cell Physiol 147:27, 1991). In this report we show that in sheep reticulocytes incubated in vitro, the majority (approximately 75%) of the released receptor is of native size and is exosome associated. A fraction (approximately 25%) is a truncated form of approximately 80 Kd corresponding to the exofacial domain of the TFR. Herein we also address the question of whether the truncated receptor originates by proteolytic cleavage directly from the cell surface or by cleavage from exosomes. Using surface 125I labeled sheep reticulocytes as the experimental model, we show that during in vitro maturation, 125I-TFR of native size appears in exosomes before the soluble, truncated, exofacial domain of the receptor is detected in the medium. Because cleavage and release of the exofacial domain would likely leave the truncated cytoplasmic and transmembrane domains in the originating membrane (plasma membranes or exosomes), both fractions were probed with antibodies specifically generated against the cytoplasmic domain of the receptor. Only exosomes, not plasma membranes, show the presence of a approximately 17-Kd peptide recognized by the antibody to the cytoplasmic domain of the transferrin receptor. Thus, it is concluded that the truncated, soluble receptor originates from exosomes in sheep. A 17-Kd cytoplasmic domain of the TFR was also detected in exosomes from the reticulocytes of an anemic man, suggesting that the truncated receptor in man may also originate from exosomes. Using in vitro cultures of surface 125I-labeled sheep reticulocytes, it is concluded that exosome formation is the principal route for maturation-associated loss of the TFR. A similar conclusion was made earlier (Johnstone et al: J Cell Physiol 147:27, 1991) for the nucleoside transporter of maturing sheep reticulocytes. PMID- 8481525 TI - Blood-feeding host preferences of the isomorphic species Simulium venustum and S. truncatum. AB - Animal-baited traps, using fox, mink, rabbits and ducks, were used in host preference experiments in two habitats (Beach and Woods). A generalized linear model of blood-feeding host preference is presented to test for significant differences between the isomorphic species Simulium venustum and Simulium truncatum. The S. truncatum population peaked before that of S. venustum. On any given day the two species divided their blood-feeding efforts among the different hosts in the same proportions. On the Beach, fox was the preferred host at the beginning of the season, but by the end of the season flies fed with equal frequency on the fox and the mink. In the Woods fox remained the preferred host throughout the season (late May to early July). Possible reasons for these feeding trends are discussed. PMID- 8481526 TI - Effects of two blood-feeding regimes on mortality and female reproduction in a laboratory colony of stable flies, Stomoxys calcitrans. AB - Stable flies (Stomoxys calcitrans L.) deprived of a bloodmeal until 3 days post emergence had higher mortality rates than control flies fed from the day of emergence. Fat bodies of deprived females required one more bloodmeal to reach maximum size, and maximum size was smaller, than fat bodies of control females. Ovarian development did not commence prior to feeding in deprived flies, and proceeded more slowly thereafter, resulting in a one blood-meal delay in egg maturation in deprived flies. Deprived females produced fewer (54.7, SD 2.8) eggs than controls (75.9, SD 3.7) and eggs from deprived females were smaller (mean length 684.0 microns) than control females' eggs (mean length 1165.7 microns). PMID- 8481527 TI - Changes in malathion and pyrethroid resistance after cypermethrin selection of Culex quinquefasciatus field populations of Cuba. AB - Use of the organophosphorus insecticide malathion for mosquito control in Cuba, for 7 years up to 1986, selected elevated non-specific esterase and altered acetylcholinesterase (AChE) resistance mechanisms in Culex quinquefasciatus. In central Havana space-spraying of malathion was replaced by the pyrethroid cypermethrin in 1987: alternate cycles of malathion and cypermethrin were applied in some of the more rural areas of Havana district during 1987-91. Consequently, populations of Cx quinquefasciatus in the central area of Havana developed resistance to cypermethrin, but there is no evidence of pyrethroid resistance in the outlying areas. Malathion resistance levels declined significantly after 1986, measured both by bioassay and the frequency of the elevated esterase resistance mechanism, and then stabilized with no measurable decline during 1990 in any of the populations tested. These populations had less than 10% frequency of susceptible homozygotes for both the esterase and AChE resistance mechanisms, indicating that organophosphate resistance is still prevalent in Cuban Cx quinquefasciatus. These two mechanisms appear to be in linkage equilibrium, suggesting that current selection for double resistance is not strong. In the central Havana region, pirimiphos-methyl, an organophosphorus insecticide unaffected by the two common malathion resistance mechanisms, is now being used in a resistance management strategy designed to avoid pyrethroid resistance spreading. PMID- 8481528 TI - Laboratory colonization of Anopheles quadriannulatus from sympatry with other sibling species of the Anopheles gambiae complex in Zimbabwe. AB - A laboratory colony of the mosquito Anopheles quadriannulatus was established from a wild population occurring sympatrically with An.arabiensis in Zimbabwe. These sibling species are members of the An.gambiae Giles complex and were distinguished primarily by means of their specific polytene chromosome banding patterns. By using an ox-baited trap, we sampled selectively for the more zoophilic An.quadriannulatus. It was confirmed that An.quadriannulatus has the diagnostic slow allozyme of aspartate aminotransferase (AAT95/95). In a mixed population under laboratory conditions, An.arabiensis displaced An.quadriannulatus within eight generations, without introgression. Colonization of An.quadriannulatus was facilitated by pooling the progeny from wild-caught mothers of confirmed identity and by using a specially adapted cage to promote mating. PMID- 8481529 TI - Malaria in urban and rural Kinshasa: the entomological input. AB - Mosquitoes were collected on human bait over a 16-month period (September 1988 to December 1989) in an urban and a rural area of Kinshasa, Zaire. P. falciparum malaria sporozoite rates were determined by ELISA. In the urban area Culex quinquefasciatus accounts for 96% of the 121 bites/person/night (b/p/n). The only anopheline is Anopheles gambiae, sensu stricto, with an average of 5.1 b/p/n and a sporozoite rate of 1.86%. The entomological inoculation rate (EIR) averages 0.08 infective b/p/n. Malaria transmission is almost interrupted at the end of the dry season. In the rural area mosquito nuisance is small (20 b/p/n), almost entirely due to six species of Anopheles including four vectors of malaria: An.gambiae (13.3 b/p/n), An.funestus (2.4 b/p/n), An.nili (0.4 b/p/n) and An.brunnipes (0.7 b/p/n) with mean sporozoite rates of 7.85%, 6.60%, 6.63% and 0.53% respectively. An.paludis (0.4 b/p/n) and An.hancocki (0.2 b/p/n) were not found infective. Malaria transmission is intense and perennial: the overall EIR varies monthly between 0.60 and 3.29 infective b/p/n. The specific contributions of An.gambiae, An.funestus and An.nili average 1.07, 0.14 and 0.03 infective b/p/n respectively. Malaria transmission peaks during the rainy season in both study areas. The daily mean survival rates for An.gambiae were 0.91 and 0.78 in the rural and urban area, respectively. All An.gambiae examined belonged to the forest cytotype (Coluzzi et al., 1979). Through its effect on the sporozoite rate, the higher vector survival rate in the rural environment appears to be the major determinant of the greater malaria transmission rate in the rural area as compared to urban Kinshasa. PMID- 8481530 TI - Lice of farm animals in Libya. AB - This first report on the lice of farm animals in Libya lists a total of fifteen species, as follows: Haematopinus quadripertusus and Linognathus vituli from cattle, Bovicola ovis, Linognathus pedalis, L. africanus and L. ovillus from sheep, L. stenopsis, L. africanus and Bovicola caprae from goats. Poultry harboured Lipeurus caponis, L. heterographus, Menacanthus stramineus, Menopon gallinae, Goniocotes gallinae, Goniodes gigas and G. dissimilis. PMID- 8481531 TI - Mean life expectancy of Old World screwworm fly, Chrysomya bezziana, inferred from the reproductive age-structure of native females caught on swormlure-baited sticky traps. AB - The reproductive status of native (wild) screwworm fly, Chrysomya bezziana, caught on swormlure-baited sticky traps in Papua New Guinea is described. A total of 1122 females and 25 males were trapped. Of these females 595 were scored for insemination status and stage of ovarian development (on a scale of 2-10) of which 20% were in suitable condition for assignment to first, second and third ovarian cycles. Of the nulliparous females, only 17% were inseminated at stage 3 of ovarian development, 70% at stage 4, 93-97% at stages 5 and 6, and all of stages 7-10 (gravids). All parous females were inseminated. More than half of the captured females were parous (58%) and only 7% of the total were gravid. Proportions of females in ovarian cycles 1, 2 and 3 were 41%, 50% and 9% respectively. Survival of female Ch.bezziana in the laboratory was adequately described by lognormal and Gompertz survival functions, for both of which the mortality rate is an increasing function of reproductive age. Analysis of the reproductive age distribution of native females estimated their mean life expectancy at 9 days under the prevailing mean field temperature of 26.5 degrees C. This equates to completion of 1.7 ovarian cycles and an estimated mean lifetime fecundity of 146 female progeny. The survival models, which also allowed responsiveness of females to swormlure-baited traps (female trappability) to vary according to their stage of ovarian development, indicated significant age dependent trapping bias. These findings are compared with similar data for the New World screwworm fly, Cochliomyia hominivorax. PMID- 8481532 TI - Habitat preferences and carcase colonization by sheep blowflies in the northern North Island of New Zealand. AB - In urban Auckland, from September 1991 to May 1992, only six specimens of the Australian sheep blowfly, Lucilia cuprina, were collected in farmed parkland and in garden habitats. The common green blowfly, Lucilia sericata, was the most common calliphorid trapped in these habitats. Neither of the two Lucilia species were found in native bush remnants in urban or rural areas where Calliphora hilli was dominant. Similarly very few L.cuprina (0.3% of the total) were trapped in rural rubbish tips in January and February where the majority of blowflies were again L.sericata. These results are compared with data collected from pastoral habitats, where L.cuprina is the major cause of flystrike. Lucilia cuprina was reared from five out of ninety-nine carcases found in rural areas. Calliphora stygia and L.sericata were the most common blowflies colonizing carrion and were reared from 59% and 51% of the carcases respectively. PMID- 8481533 TI - A trial to control the tsetse fly, Glossina morsitans centralis, with low densities of odour-baited targets in west Zambia. AB - A large-scale trial investigated the possibility of eradicating G.m.centralis from a traditional cattle rearing area using odour-baited targets at a reduced overall target density from 4 to 0.5-2.3 per km2, thus cutting down initial material costs by about 50%. Only the periphery of what was thought to be prime tsetse habitat (dense woodland) was treated with targets. These were all black or blue/black cloth (1.8 x 1 m), sprayed with deltamethrin suspension concentrate and baited with butanone and/or acetone (40-130 mg/h) and 1-octen-3-ol (0.5 mg/h). Although fly catches from traps and flyrounds initially dropped by approximately 3% per day and trypanosomiasis cases declined by 99% within a year, eradication was not achieved, so that more targets were deployed at a later stage. Although initially cheaper, the option of using reduced target densities proved financially unattractive because of prolonged periods of target maintenance prior to eradication. Revised strategies for tsetse control with odour-baited, insecticide-impregnated targets in west Zambia are presented. PMID- 8481534 TI - Aspects of sandfly biology in southern Switzerland. AB - During three field surveys of phlebotomine sandflies in the region of Sessa, Minor Malcantone, southern Switzerland, annually 1987-89, Phlebotomus perniciosus and P. mascittii were caught regularly by means of light traps, but only when the traps were in close association with humans. The most productive catching sites were in the middle of Sessa village, in basements or partially closed shelters in the immediate vicinity of human dwellings. All catching sites outside the village were negative. The only other sandfly species caught was Sergentomyia minuta, four specimens only. P.perniciosus and P.mascittii always occurred together and were found to feed--at least occasionally--on human blood. Glucose and fructose were identified in wild-caught sandflies of both species. A breeding place of P. mascittii was identified in the basement of a house in the middle of Sessa. Analyses of soil samples revealed moderately loamy humus with a slightly acidic pH (5.6). PMID- 8481535 TI - Uptake and fate of specific antibody in feeding larvae of the sheep blowfly, Lucilia cuprina. AB - The quantity of specific antibody ingested by larvae of Lucilia cuprina and its fate after ingestion were studied in larvae grown on sheep and on an artificial diet. Larvae grown to late first or early second instar on sheep vaccinated with horse myoglobin contained 66% less specific antibody detected by enzyme linked immunosorbent assay than larvae grown to a similar stage on an artificial diet containing 75% serum from the same sheep. A similar result was obtained when larvae were grown to mid-third instar. Larvae grown on sheep to first or second instar contained approximately the same quantity of specific antibody per unit weight of larvae as those grown to third instar. Larvae grown on diet to third instar contained 22% less specific antibody per unit weight than those grown to first or second instar. In larvae grown on diet to late third instar, ingested diet retained 91 +/- 12% of its original specific antibody activity in the crop, 50 +/- 11% in the anterior midgut, 8 +/- 2% in the posterior midgut and 13 +/- 6% in the hindgut. The mean concentration of total immunoglobulin detectable in the haemolymph of individual third instar larvae grown on diet was 1.7 +/- 2.8 micrograms/ml. Assays of specific antibody in the haemolymph of similarly reared larvae indicated that all or most of this immunoglobulin remained functional. The implications of the quantities and distribution of ingested functional antibody found in feeding larvae of L.cuprina are discussed in relation to the possibility of vaccinating sheep against these larvae and the selection of likely internal targets as sources of potential protective antigens. PMID- 8481536 TI - Changes in immunity to Ixodes ricinus by rabbits infested at different levels. AB - Two groups of rabbits were infested twice with different numbers of Ixodes ricinus adults: one group (high infestation) with twenty-five females and twenty five males and the other group (low infestation) with five pairs. A third infestation was performed in both groups with fifteen adult pairs. Tick biology was monitored for resistance effects. At the second infestation, the feeding and the egg production were more perturbed in ticks fed on high infestation rabbits. The embryogenesis was only affected in ticks from high infestation rabbits. At the third infestation, resistance was increased only in low infestation rabbits, which became more resistant than high infestation rabbits. The blastogenic response of peripheral blood lymphocytes and antibody production against ticks were assessed. A salivary gland extract and an integumental antigen from I. ricinus adult females were able to initiate lymphocyte proliferation. The response was significantly higher in high infestation rabbits, especially at the end of the second infestation, and higher in low infestation rabbits during the third infestation. Non-specific proliferation with concanavalin A was temporarily decreased in both rabbits groups during the first and the second infestations. Specific antibody response to salivary and integument antigens were always the highest in high infestation rabbits. The involvement of tick-induced immunosuppression is discussed. PMID- 8481537 TI - Enhancement of tick-borne encephalitis virus transmission by tick salivary gland extracts. AB - To investigate the role of ticks in TBE virus transmission, salivary gland extract (SGE) was derived from partially fed female Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus appendiculatus ticks. Guinea-pigs were infested with uninfected R. appendiculatus nymphs and inoculated with a mixture of TBE virus and SGE or with virus alone. The number of ticks which on average acquired virus from feeding on animals inoculated with TBE virus and SGE from partially fed ticks was 4-fold greater than the number that became infected by feeding on animals inoculated with virus alone or virus plus SGE from unfed I. ricinus. Viraemia was detected in 67% of guinea-pigs inoculated with virus plus SGE compared to 30% of guinea-pigs inoculated with virus alone. Virus titres in the blood were similar for both groups of animals [range 2.0-2.8 log10 plaque-forming units (PFU)/ml of blood]; however, the number of ticks that became infected was significantly higher on animals inoculated with virus plus SGE from partially fed ticks. No significant difference was observed with respect to the tick species used to derive SGE. The results indicate that TBE virus transmission is enhanced by factor(s) associated with the salivary glands of feeding ticks, and that these factor(s) may facilitate efficient transmission of TBE virus between infected and uninfected ticks even when they feed on hosts that have no detectable viraemia. PMID- 8481538 TI - The effect of dung beetle activity on the discharge of Pilobolus sporangia in cattle faeces. PMID- 8481539 TI - Antisense DNA oligonucleotides. I: The use of ionspray tandem mass spectrometry for the sequence verification of methylphosphonate oligodeoxyribonucleotides. AB - The sequences of synthetically prepared methylphosphonate oligodeoxyribonucleotides have been verified using ionspray tandem mass spectrometry with sample introduction via flow injection. The technique involves the use of product-ion scans from multiply protonated (4+ and 5+) precursors. Among the ions detected are several series of fragments of different charge states that indicate the base sequence of the intact molecule. Oligomers as large as 18 bases have been successfully characterized. PMID- 8481540 TI - Antisense DNA oligonucleotides. II: The use of matrix-assisted laser desorption/ionization mass spectrometry for the sequence verification of methylphosphonate oligodeoxyribonucleotides. AB - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has been used to measure accurately the molecular masses of synthetic methylphosphonate oligodeoxyribonucleotides, up to 18 nucleotides in length. A simple method has been developed for the complete sequence verification of these compounds, which are intractable by classical means. Sequencing from the 5' end of the molecule is possible because of inefficiencies in the synthetic procedure. Complementary information from the 3' end can be obtained by partial hydrolysis of the methylphosphonate backbone. PMID- 8481541 TI - Chemical archaeology of kava, a potent brew. AB - Kava lactones, which are present in the intoxicating Pacific Island drink, kava, have now been detected in a number of archaeological artefacts using selected-ion monitoring techniques in conjunction with gas chromatography/electron impact-mass spectrometry. Thus it is now possible to link unequivocally kava drinking, a major aspect of the ceremonial culture of many Pacific societies, to the archaeological record. In addition, a new variation of the kava lactone skeleton was tentatively identified in the form of 7,8-dihydro-5,6-dehydrokawain and 7,8 dihydro-5,6-dehydromethysticin. PMID- 8481542 TI - In situ reduction suitable for matrix-assisted laser desorption/ionization and liquid secondary ionization using tris(2-carboxyethyl)phosphine. AB - The suitability of the hydrochloride salt of tris(2-carboxyethyl)phosphine (TCEP) for in situ reduction with matrix-assisted laser desorption/ionization (MALDI) and liquid secondary ionization (LSI) mass spectrometry is evaluated. TCEP can be used to irreversibly reduce organic disulfides to thiols in water and is active at an acidic pH. We found that TCEP was suitable for partial reduction of bovine insulin deposited on the target and mixed with either sinapinic acid in MALDI or glycerol and m-nitrobenzyl alcohol in LSIMS. When TCEP was added to insulin deposited on the target without prior mixing of sinapinic acid the in situ MALDI protocol resulted in almost complete reduction. PMID- 8481543 TI - Sequence-ion studies in peptides: the generation of C" ions. AB - The mechanism for the formation of C"-type ions from protonated peptides, produced under conditions of fast-atom bombardment and collisional activation was investigated. Comparison of the tandem mass spectra of the [M + H]+ ions of a model peptide and the corresponding [Md + D]+ ions, in which all exchangeable hydrogens are replaced with deuterium, revealed that neither the carboxylic hydrogen nor a hydrogen from a nitrogen atom is involved in the process of migration of a hydrogen which leads to the formation of C"n-type ions. The most feasible position from which the transferred hydrogen originates is that at the first C-atom in the side-chain of the adjacent amino acid. PMID- 8481544 TI - The ethnic distribution of antibodies to glutamic acid decarboxylase: presence and levels of insulin-dependent diabetes mellitus in Europid and Asian subjects. AB - Our objective was to ascertain the frequency of antibodies to glutamic acid decarboxylase (GAD) in Europids and four Asian ethnic groups with insulin dependent diabetes mellitus (IDDM) to gain insight into why the prevalence and incidence of IDDM varies so widely among ethnic and/or geographically diverse population groups. The subjects in this study were Europid (n = 49), Japanese (n = 16), Thai (n = 7), Korean (n = 21), and Chinese (n = 13) persons with IDDM with a duration ranging from 5 to 14 years. There were similar numbers of healthy controls matched for each ethnic group. A validated radioimmunoprecipitation assay used GAD from pig brain radiolabeled with 125I using chloramine T. Islet cell cytoplasmic antibodies measured by indirect immunofluorescence were expressed as Juvenile Diabetes Foundation units. The prevalence of antibodies to GAD, compared with Europids (63%), was much lower in all Asian populations with IDDM: Japanese (31%), Thai (29%), Korean (5%), and Chinese (27%). The mean level of antibodies to GAD, however, among diabetics from each population who gave a positive reaction, was similar. For all groups, the prevalence of antibodies to GAD was much higher than that of islet cell cytoplasmic antibodies. Almost all IDDM subjects positive for islet cell antibodies had antibodies to GAD, but the converse did not hold. A radioimmunoprecipitation assay for antibodies to GAD applied to serum from subjects with IDDM in various ethnic groups showed that Europids with IDDM had a much higher prevalence of such antibodies than did Asians. This held for all ethnic groups, and particularly Koreans. Thus, among different populations, there may be etiologic heterogeneity of IDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481545 TI - Is growth hormone associated with diabetic retinopathy? AB - The role of growth hormone (GH) in the pathogenesis of diabetic retinopathy was evaluated in 150 patients with non-insulin-dependent diabetes mellitus by measuring urinary GH excretion using a highly sensitive enzyme immunoassay. Urinary GH excretion was not significantly different among diabetic patients without retinopathy (mean, 2.4 ng/day; range, < 0.3-20.0 ng/day), with background retinopathy (2.7 ng/day; < 0.3-22.0 ng/day), and with proliferative retinopathy (3.1 ng/day, 0.9-15.6 ng/day). These data suggest that GH does not play a role for the pathogenesis of diabetic retinopathy through the increased physiological secretion. PMID- 8481546 TI - Type I diabetic nephropathy: clinical characteristics and economic impact. AB - Approximately one-third of type I diabetic patients develop diabetic nephropathy with confounding pathogenesis--frequently manifested as heavy persistent proteinuria, fall in glomerular filtration rate, and increased arterial hypertension. There is increasing incidence and prevalence of type I diabetes, particularly in northern Europe and the United States. Increased morbidity and mortality occur in type I diabetic patients with renal disease. Among type I patients with persistent proteinuria, death occurs on the average within 5-10 years. The economic impact of endstage renal disease due to diabetic nephropathy is overwhelming, and the cost is increasing at an alarming rate. PMID- 8481547 TI - Renal hypertrophy as a prognostic index for the progression of diabetic renal disease in non-insulin-dependent diabetes mellitus. AB - The aim of this study is to elucidate the clinical significance of estimating renal size in non-insulin-dependent diabetes mellitus (NIDDM). Renal size was compared in 57 NIDDM patients with persistent normoalbuminuria [group I; 19 cases, albumin excretion rate (AER) < 20 micrograms/min], microalbuminuria (group II; 24 cases, AER = 20-200 micrograms/min), or macroalbuminuria (group III; 14 cases, AER > 200 micrograms/min). Three groups were matched for age and diabetes duration. Renal size was estimated using drip-infusion pyelography according to Simon's method (mean kidney length/height of second lumbar spine and disc; renal ratio, RR). Thirteen patients with persistent microalbuminuria (10 normotensive and 3 hypertensive) were traced during at least 3 years. Angiotensin-converting enzyme inhibitor (enalapril) was used in 11 cases. The results are as follows: (1) Renal size in groups II (RR, 3.47 +/- 0.28; cited as mean +/- SD) and III (3.62 +/- 0.32) significantly increased compared with that in group I (3.26 +/- 0.20) (p < 0.01 and p < 0.001, respectively). No statistical differences could be detected between groups II and III. (2) As a whole, good metabolic (glycosylated hemoglobin, HbA1) and hemodynamic (systolic blood pressure, SBP) control was achieved during the last 12 months (HbA1, 8.4% +/- 0.9%; SBP, 122 +/- 8 mm Hg). There was no significant correlation between RR and creatinine clearance, HbA1, SBP, or diastolic blood pressure during the first and last 12 months. Initial RR significantly correlated with AER during the last 12 months (r = 0.651, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481548 TI - Audit of the change from twice daily to basal-bolus insulin regimens in insulin dependent diabetes. AB - Basal-bolus insulin regimens have become popular with patients, but clinicians' enthusiasm for their use has been tempered by a number of reports that suggest that these regimens do not improve overall glycemic control when compared with conventional, twice daily, regimens. Indeed, it has been suggested that basal bolus regimens may be abused by certain patients leading to an increase in body weight and deterioration in glycemic control. This paper reports the results of a retrospective audit of 145 insulin-dependent diabetic patients changed from conventional insulin therapy to a basal-bolus insulin regimen. After 3 months on the basal-bolus regimen, a small but significant fall in total insulin (10%; p < 0.001) and intermediate-acting insulin (50%; p < 0.001) dose was recorded. During this time period serum fructosamine measurements also fell by 10% (p < 0.001) indicating a small but significant improvement in glycemic control. Body-mass index (BMI) and body weight data did not support the view that basal-bolus regimens lead to an increase in body weight. Analysis of the data by gender did not support the view that the basal-bolus insulin regimen is prone to abuse by female patients. PMID- 8481549 TI - Association of thermal perception thresholds with cardiovascular autonomic function in diabetes. AB - In order to study the association between warm thermal-perception thresholds (WPT), cold thermal-perception thresholds (CPT) and cardiovascular autonomic function, we examined 91 otherwise healthy patients with diabetes mellitus (69 with type I and 22 with type II). The covariance analysis revealed that WPT was associated with the deep-breathing E/I ratio and the Valsalva ratio (p = 0.004 and p = 0.008, respectively) whereas CPT was associated with the Valsalva ratio and the postural blood pressure decrement (p = 0.008 and p = 0.004, respectively). These associations possibly reflect histological similarities between the parasympathetic nerves and those mediating warm sensation, and between the sympathetic nerves and those mediating cold sensation. PMID- 8481550 TI - Taurine prevents galactose-induced cataracts. AB - Intact lenses from New Zealand white rabbits were incubated in tissue culture media containing either 5 mM glucose or 5 mM glucose plus 30 mM galactose. The standard media did not contain taurine. Lenses were also cultured in a third medium containing 30 mM galactose plus 0.2 mM taurine. The frequency of cataract formation was evaluated as a function of the culture media. One lens (1/10), in media containing 5 mM glucose, developed a lenticular opacification during a 72-h incubation. Lenses (12/15) incubated in 30 mM galactose, without taurine, developed cataracts; fewer lenses (2/13) exposed to 30 mM galactose plus 0.2 mM taurine developed cataracts (p < 0.005). Galactose cataracts have been associated with lens edema attributed to the osmotic stress of tissue polyol (galactitol) accumulation. The water content of the noncataractous and cataractous lenses in this experiment did not differ. Lens edema, therefore, was not thought to be important in cataract pathogenesis. Taurine, an organic osmolyte was lower (5.1 +/- 1.5 mumol/g protein) in cataractous lenses than in control lenses (10.0 +/- 1.0 mumol/g protein). Malondialdehyde, an indicator of lipid peroxidation, was higher (36.6 +/- 5.0 mumol/g protein) in lens-containing opacifications than in noncataractous lenses (10.1 +/- 1.9 mumol/gm protein) (p < 0.01). The levels of malondialdehyde suggest that lipid peroxidation was increased in the process of sugar cataractogenesis. The malondialdehyde content of all the lenses correlated inversely (r = -0.53, p < 0.01) with the coincident lens taurine levels. Taurine appears to protect the lens against the development of sugar cataracts; its inverse relationship with lens malondialdehyde suggests this is an antioxidant effect. PMID- 8481551 TI - The predictive value of albuminuria for cardiovascular and renal disease. A 5 year follow-up study of 476 patients with type I diabetes mellitus. AB - A 5-year follow-up study of 476 type I adult diabetic patients previously studied cross sectionally revealed that, during the observation period, 19 patients died and 30 developed cardiovascular or renal disease, such as myocardial infarction (n = 8), cerebrovascular disease (n = 3), amputation (n = 6), and renal insufficiency (n = 13). The patients were registered by one and the most-severe event only. The yearly death rate was 8.0 per 1000, compared with the expected death rate of 2.0 for people with corresponding age and sex in the general population. In patients with renal insufficiency, one also had myocardial infarction, and one had had an amputation. The ages of patients who died, with myocardial infarction, cerebrovascular disease, amputation, or renal insufficiency, were 44.2 +/- 12.7, 41.3 +/- 6.6, 43.7 +/- 13.2, 45.3 +/- 15.7, and 40.8 +/- 9.8 years, respectively. Urinary albumin concentration in a single early morning urine sample was found to be a strong prognostic marker for the development of cardiovascular disease or death. In contrast, age, gender, age at onset and duration of diabetes, levels of blood pressure, serum creatinine, and HbA1c, or presence of hypertension, as well as changes in blood pressure and hBa1c, during the observation period did not influence the survival or incidence of cardiovascular disease. However, blood pressure and HbA1c were associated with increased urinary albumin concentrations during the follow-up period. PMID- 8481552 TI - Oral health and salivary composition in diabetic patients. AB - The salivary composition and flow rate were examined in 20 patients with insulin dependent diabetes mellitus (IDDM) and in 19 patients with non-insulin-dependent diabetes mellitus (NIDDM) and compared with 20 healthy controls. Resting and stimulated whole and submandibular saliva was analyzed. Significantly lower resting salivary flow rates were found in the IDDM patients as compared to the NIDDM group. In the IDDM patients potassium concentration in resting saliva was significantly higher compared with healthy controls and in stimulated whole saliva compared with NIDDM patients. No difference in salivary total protein, amylase, lactoferrin, or lysozyme was found among the three groups examined. The IgA concentration of the IDDM patients was significantly higher in whole resting saliva compared with controls and in the submandibular saliva compared with both NIDDM patients and controls. No difference was found between controls and the diabetic patients examined in prevalence of complaint of dry mouth. The salivary flow rates, however, were significantly lower in the three subgroups with dry mouth compared with the subgroups without this complaint. Caries were detected in 100% of the diabetic patients and controls. No correlation was observed between the incidence of caries and any of the salivary parameters examined. A higher prevalence and severity of periodontal disease was detected in the diabetic patients as compared to the controls. A significant positive correlation was found between the gingival index and the concentrations of total protein, albumin, lysozyme, and lactoferrin in whole resting saliva in the three groups examined. PMID- 8481553 TI - Rapidly progressing diabetic retinopathy upon improved metabolic control. PMID- 8481554 TI - Fecal excretions of hydroxy fatty acid and bile acid in diabetic diarrheal patients. AB - Thirteen normal subjects, 5 diarrheal controls (Group I) and 13 diabetics without peripheral neuropathy (Group II) were compared with 7 diabetic patients (Group III) with respect to fecal excretions of bile acids and hydroxy fatty acids for pathogenesis of diabetic diarrhea. The mean fecal excretions of bile acids per day were 304.9 mg for the normal controls, 297.8 mg for Group I, and 382.4 mg for Group II, while those of Group III were significantly higher (958.2 mg, p < 0.01) than the foregoing groups, and nearly three times as much as the controls. As to the fecal fatty acid excretion, there were no significant differences observed among these groups. The percentages of fecal hydroxy fatty acids were not significantly different in normal subjects (1.5%), Group I (2.0%), and Group II (1.2%). In contrast, the percentage of hydroxy fatty acid for Group III was greatly (p < 0.01) increased (13.2%). From the above results, the percentage of hydroxy fatty acid in diabetic diarrheal patients was high, suggesting that there is bacterial overgrowth. Meanwhile, the fecal bile acid level was increased about three times, indicative of poor absorption of bile acid from mild to moderate degree. Therefore, it is considered improbable that fecal hydroxy fatty acids and bile acids are the cause of diabetic diarrhea. PMID- 8481555 TI - Methods for the analysis of enantiomers of racemic drugs application to pharmacological and pharmacokinetic studies. AB - Although the existence and differences in biological behavior of optical isomers have long been appreciated, there has been an apparent reluctance to address these differences in pharmacology and the pharmaceutical sciences. At least part of this reluctance arises from the belief that the separation of enantiomers requires highly specialized analytical equipment and expertise. The purpose of this review is to present general principles that allow the separation of stereoisomers and demonstrate that these procedures can be accomplished using available and convenient chromatography techniques. PMID- 8481556 TI - Approaches to the identification and classification of chemical allergens in mice. AB - During the last 10 years understanding of the immunobiological mechanisms whereby chemicals induce allergy has increased significantly. In parallel there have emerged opportunities to develop alternative methods for the prospective identification and classification of chemical contact and respiratory allergens. Attention has focused largely on the mouse, and several novel approaches to the identification of contact allergens have been described, among them the local lymph node assay, the mouse ear swelling test and, most recently, the noninvasive mouse ear swelling assay (MESA). Progress has been made also in defining methods for measuring respiratory sensitization potential in mice. Recent evidence indicates that respiratory and contact allergens provoke qualitatively different immune responses characteristic of selective T helper (Th) cell activation. Evaluation of the nature of immune responses induced in mice by chemicals may permit not only assessment of allergenic potential, but also prediction of the form allergic reactions will take. PMID- 8481557 TI - A new method for assessing Ca2+ requirements for vasoconstriction in the rat isolated perfused kidney. Effect of norepinephrine and endothelin. AB - The consecutive perfusion with three different media containing 1) a high-K+, Ca(2+)-free solution with 1 mM of EDTA, 2) a high-K+, Ca(2+)-free solution with 1mM of EDTA and 0.3-10 microM of norepinephrine (NE) or 1-10 nM of endothelin (ET), and 3) a normal K+ solution without EDTA, NE, or ET, respectively, produced three rapid and transient vasoconstrictions of the isolated and perfused rat kidney. Results obtained from preincubation with prazosin (0.9 nM) and nifedipine (10 nM) or reperfusion at various Ca2+ concentrations showed that the responses involved are characterized by a different mobilization of cellular and extracellular Ca2+. The first phase greatly depends on the influx of extracellular Ca2+ and/or membrane Ca2+ through voltage-dependent channels, the second from mobilization of intracellular Ca2+, while the third is due mainly to the influx of extracellular Ca2+ through receptor-activated channels. NE elicited Ca2+ mobilization from both cellular and extracellular sources through activation of alpha-1 adrenoceptors. ET is particularly effective in producing extracellular Ca(2+)-dependent vasoconstriction in a prazosin-resistant manner. Present results show that this method could be suitable to distinguish different Ca2+ requirements for spasmogen-induced vasoconstriction in the isolated and perfused rat kidney. PMID- 8481558 TI - A new cannula-inserting method for measuring vascular responsiveness. Separate intraluminal and extraluminal perfusion of canine basilar artery. AB - We modified the cannula-inserting method to examine the difference in response of vessels to intraluminal or extraluminal application of vasoactive substances. A polyethylene roof was designed to cover the isolated canine basilar artery so that an extraluminal superfusion stream could pass over an artery that simultaneously received an intraluminal perfusion. An extraluminal administration of KCl produced a monophasic transient vasoconstriction, but intraluminal KCl produced relatively small tonic constriction even at high concentrations. Serotonin-induced vasoconstrictions were significantly larger with intraluminal administration than with extraluminal. Prostaglandin F2 alpha-induced vasoconstriction exhibited no significant difference between the administration routes. Endothelin caused a long-lasting constriction, which was slightly larger in extra- than intraluminal administration. Our modified cannula-inserting technique provides a new method to examine the different effects produced by intraluminal and extraluminal application of drugs. PMID- 8481559 TI - Comparison of liposome fusion and electroporation for the intracellular delivery of nonpermeant molecules to adherent cultured cells. AB - Intracellular delivery of nonpermeant molecules to cultured cells in situ can be problematic. This work is a comparison between two methods of accomplishing this delivery; liposome-mediated delivery and electroporation. The final goal was to examine the effects of the glutathione S-transferase (GST) inhibitor Basilen Blue (BB) on glyceryl trinitrate biotransformation in porcine kidney epithelial (PK1) cells after intracellular delivery. Initial evaluation used the fluorescent markers carboxyfluorescein and lucifer yellow (LY). This was followed by biochemical analysis of glyceryl trinitrate biotransformation. Liposome-mediated delivery proved ineffective in spite of variations in the lipid composition of the liposomes and the use of an agglutinin and a fusogen. In contrast, electroporation was a very effective method for intracellular delivery of both lucifer yellow and basilen blue to the PK1 cells. The results show that in cells where Basilen Blue was introduced, there was a decrease in both the glyceryl trinitrate (GTN) biotransformation and ratio of glyceryl-1,2-dinitrate (1,2-GDN) to glyceryl-1,3-dinitrate (1,3-GDN) formed. The technique of in situ electroporation shows great promise for the assessment of a variety of nonpermeant molecules of pharmacological interest. PMID- 8481560 TI - Is pentobarbital appropriate for basal anesthesia in the working rat heart model? AB - In the present study we have examined the effects of the general anesthetic agents for the excision of the heart on the hemodynamic function of the ischemic perfused heart. Animals were divided into three groups. In one group rats were anesthetized with sodium pentobarbital intraperitoneally. Animals of the second and third groups were anesthetized with inhalation anesthetics, sevoflurane and isoflurane, respectively. The hearts were then rapidly excised and perfused by a working heart model. After control perfusion, whole-heart ischemia was induced by one-way aortic valve for 15 min followed by reperfusion for 30 min. During preischemic control period, cardiac output (CO) and left ventricular dP/dT maximum (LV dP/dT max) in the isoflurane group were significantly higher than those in the pentobarbital group. During reperfusion, CO and LV dP/dT max in the isoflurane and sevoflurane groups recovered more rapidly than those in the pentobarbital group. Although there were no significant differences in myocardial ATP and glycogen levels among the groups, myocardial lactate in the pentobarbital group was significantly higher than those in the sevoflurane and isoflurane groups. These results suggest that intraperitoneal pentobarbital anesthesia, administered prior to heart excision, may affect the performance of the ischemic perfused heart thereafter. Therefore, we would suggest that isolation of hearts by means of inhalation anesthesia is better than by means of pentobarbital in the working rat heart. PMID- 8481561 TI - Reproducibility of the model of induced ventricular tachycardia in conscious dogs with infarction. AB - The canine model of ventricular tachycardias (VT) induced by programmed stimulation is used routinely in several laboratories to test antiarrhythmic drugs. The aim of the present study was to determine the rate of success and reproducibility of this model. We analyzed a group of 58 dogs that underwent a 2 hr occlusion and were submitted to programmed electrical stimulation at least 4 days after the surgery. Only 29 dogs (50%) were inducible and included in the study, as 22 dogs died following myocardial infarction, and seven dogs were never inducible. Out of 130 trials, 92 (70%) performed on inducible dogs were positive with 11% of nonsustained ventricular tachycardias, 63% of sustained monomorphic ventricular tachycardias, and 26% of ventricular fibrillation. Inducibility decreased over time in a subgroup of 19 dogs that was submitted to four trials during the first month after the infarction (68% of inducible dogs versus 46% in trials 1 and 4, respectively). Ventricular effective refractory period decreased significantly from 146 +/- 7 msec at trial 1 to 114 +/- 6 msec at trial 4, and the severity of the induced ventricular tachycardias increased. This variability should be considered when planning studies on antiarrhythmic drugs in this model. PMID- 8481562 TI - Familial recurrence risks and inheritance of multiple sclerosis. AB - The cause of multiple sclerosis is unknown. There is considerable circumstantial evidence that multiple sclerosis is a complex trait, probably autoimmune in nature, and is determined by both genetic and environmental factors. It is recognized that relatives of multiple sclerosis patients are at greater risk for developing the disease than the general population, although this risk is still relatively low in absolute terms. Monozygotic co-twins of multiple sclerosis patients appear to have the highest risk of any group of relatives, although the absolute risk is well under 100%, as would be predicted if multiple sclerosis is purely a genetic disorder. PMID- 8481563 TI - Hormonal factors in susceptibility to multiple sclerosis. AB - Evidence implies that hormonal factors are involved in susceptibility to multiple sclerosis. Diseases associated with a class II allele occur more frequently in women than in men. Multiple sclerosis is more frequent in women, particularly in the early- and late-onset groups. Pregnancy has a favorable effect on the course of multiple sclerosis on both a short- and a long-term basis. Experimental allergic encephalomyelitis, an animal model with similarities to multiple sclerosis, is also influenced by hormonal factors in both occurrence and severity. The multiple levels of interaction between immune, endocrine, neurologic, and genetic systems probably explain the action of sex steroids in multiple sclerosis susceptibility. PMID- 8481564 TI - Magnetic resonance in multiple sclerosis. AB - Magnetic resonance and various chemical measurements, such as spectroscopy, are being systematically applied to both multiple sclerosis and the experimental model (experimental allergic encephalitis). The dynamic aspects of multiple sclerosis pathology can be visualized on serial magnetic resonance imaging scans, and enhancement techniques help distinguish another type of activity by showing a leaky blood-brain barrier in acute lesions. Quantitative measures applied to the image also appear to provide an index of the burden of disease both in individual patients and in groups. A combination of the dynamic information available from serial studies and the quantitative information concerning burden of disease promises to provide both sensitivity and objectivity to standard outcome measures in multiple sclerosis. In addition, natural history studies of the evolution of magnetic resonance imaging and spectroscopy will revolutionize our understanding of the evolution of the actual tissue changes in multiple sclerosis pathology that can be characterized during life. PMID- 8481565 TI - Clinical trials in multiple sclerosis. AB - In this past year, there has only been modest progress in the search for an effective treatment for multiple sclerosis and its complications, although a number of carefully designed trials are in progress. No treatment predictably slows the course of active disease. The marginal benefits previously claimed for azathioprine have been strengthened by a meta-analysis of previously published work. Methylprednisolone may have a minor role in the treatment of very severe, acute optic neuritis but prednisone use may predispose patients to recurrent optic neuritis. 4-Aminopyridine and 3,4-diaminopyridine may prove useful for the symptomatic treatment of some multiple sclerosis patients; pemoline may be an alternative to amantadine for the control of fatigue; and acetazolamide may be an alternative to carbamazepine and phenytoin for the treatment of painful tonic spasms. PMID- 8481566 TI - Clinical aspects of epilepsy including diagnosis, management, pharmacotherapy, and surgery. AB - This review emphasizes clinical manifestations, recognition of specific epileptic syndromes, use of antiepileptic drugs, and surgical evaluation and outcome. Juvenile myoclonic epilepsy is increasingly recognized but still underdiagnosed. Good evidence exists for a relationship between Landau-Kleffner syndrome (acquired epileptic aphasia) and electrical status epilepticus during sleep, which reflects the course of the aphasia. In focal onset seizures, the type of aura may be as valuable for determining the lobe of seizure onset as electroencephalographic and neuroimaging techniques. In temporal lobe seizures, postictal language assessment was used to determine the side of origin, and hippocampal and temporal volumetry using magnetic resonance imaging proved reliable indicators of the side of involvement. Valproate sodium and carbamazepine were equally effective for secondarily generalized tonic-clonic seizures, but carbamazepine was superior to valproate for complex partial seizures. One study suggests that in children, increased daytime sleep tendency persists 4 to 5 months after discontinuation of antiepileptic drugs and that neither drugs nor seizure activity are necessarily involved. Many recent publications were devoted to surgical treatment. The main issues reviewed concern patient selection and correlation between preoperative parameters and outcome after surgery. PMID- 8481567 TI - Clinical neurophysiology, neuroimaging, and the surgical treatment of epilepsy. AB - Improved neurodiagnostic tools for examining cerebral structure and function have greatly enhanced the safety and efficacy of surgical treatment for epilepsy, and markedly increased the number of candidates for these surgical interventions. The application of new developments in clinical neurophysiology, as well as recent advances in neuroimaging, for surgical therapy of medically refractory seizures are reviewed. Improvements in surgical results are documented and future directions are discussed. PMID- 8481568 TI - Pain and disorders of consciousness. PMID- 8481569 TI - HIV and interventional radiology: a national survey of physician attitudes and behaviors. AB - PURPOSE: The frequency of parenteral and cutaneous exposure to blood or body fluid during interventional radiologic procedures, current use of barrier precautions by interventional radiologists, and physician attitudes about testing for the human immunodeficiency virus (HIV) and related issues were assessed. MATERIALS AND METHODS: An anonymous survey of interventional radiologists was conducted by mail in November 1991. RESULTS: Of 1,530 surveys, 819 (54%) were returned and 806 (53%) were completed and evaluable. Ninety-six percent of respondents (763 of 794) perform procedures in patients infected with HIV. Sixty nine percent oppose mandatory testing of physicians for HIV. Eighty-seven percent (693 of 797) reported at least one procedure-related injury (range, 0-99; mean, four). Fifty-eight percent of injuries occurred with use of a sharp instrument (381 of 662), 20% were due to needle recapping (133 of 662), and 7% (44 of 662), to improper disposal of a sharp instrument. Contact between a physician's blood and a patient was reported in only one case (0.2%). Eighty-five percent of respondents (671 of 789) changed their use of barrier precautions in the last 10 years; concerns about HIV were cited by 96% as a reason for change. Reported use of barrier measures was highly variable. CONCLUSION: Exposure to patients' blood or body fluid is not infrequent during interventional radiologic procedures. Exposure of patients to the blood or body fluid of health care workers is rare. Use of recommended precautions in interventional radiology is variable, and practices that could lead to preventable injury remain common. Strategies should be developed to reduce risks even further and to encourage universal compliance with government guidelines. PMID- 8481570 TI - Endovascular treatment of arteriovenous fistulas arising from branches of the subclavian artery. AB - PURPOSE: The goal of this study was to evaluate the role of endovascular techniques in the treatment of arteriovenous fistulas (AVFs) in the subclavian region. PATIENTS AND METHODS: Since 1984 six patients with AVFs arising from branches of the subclavian artery have been treated. All AVFs were of iatrogenic origin (five venous punctures and one pacemaker insertion). Two patients had cardiac insufficiency, three had a bruit, and one had upper extremity venous hypertension. Angiographically, four of the AVFs were located on the thyrocervical trunk and two were on the internal mammary artery. RESULTS: All fistulas were treated by means of endovascular occlusion with a detachable balloon, with full resolution of symptoms. One AVF recurred after a balloon deflated prematurely. The patient was treated again and was subsequently cured. No other complications were associated with treatment. CONCLUSION: Endovascular balloon occlusion of AVFs in the subclavian region is a simple, effective, and safe method that eliminates the need for surgery. It should be the method of choice for treatment of these lesions. PMID- 8481571 TI - Transcatheter embolization of a superior mesenteric artery pseudoaneurysm and arteriovenous fistula. PMID- 8481572 TI - Fragmentation of biliary calculi in 71 patients by use of intracorporeal electrohydraulic lithotripsy. AB - PURPOSE: Failure of percutaneous or endoscopic removal of biliary calculi is often associated with impacted stones or stones larger than 1.5 cm. In these difficult cases, intracorporeal electrohydraulic lithotripsy (EHL) is a method that allows large stones to be fragmented and removed percutaneously or endoscopically. In this study, the authors expand their experience with EHL and further evaluate the safety and efficacy of this technique to remove biliary tract calculi. PATIENTS AND METHODS: Intracorporeal electrohydraulic lithotripsy was used to treat 71 patients with calculi in the bile ducts (n = 35) or gallbladder (n = 36). Access was obtained by means of a surgical T-tube tract (n = 16), percutaneous transhepatic biliary drainage (n = 14), percutaneous cholecystostomy (n = 36), an intraoperative approach during common duct exploration (n = 2), and at endoscopic retrograde cholangiopancreatography (n = 3). RESULTS: EHL lithotripsy was effective in fragmenting all biliary stones in 69 of the 71 patients (97%). All of the stone fragments were removed in 67 of these 69 patients (94%). Major complications, including bile peritonitis and gallbladder necrosis, occurred in five patients; however, all major complications were related to the initial percutaneous drainage or tract dilation. No significant complications were directly attributable to the EHL procedure. CONCLUSION: Intracorporeal EHL is a safe and effective method that can be used to improve the success of percutaneous and endoscopic biliary calculi removal. PMID- 8481573 TI - Budd-Chiari syndrome: recanalization of an occluded hepatic vein with percutaneous transluminal angioplasty and a metallic stent. PMID- 8481574 TI - Treatment of Budd-Chiari syndrome with a transjugular intrahepatic portosystemic shunt. PMID- 8481575 TI - Vasa vasorum changes following stent placement in experimental arterial stenoses. AB - PURPOSE: Experimental stenoses were created in canine aortae to compare the effects of stent placement and balloon angioplasty on the vasa vasorum. MATERIALS AND METHODS: A balloon-expandable Palmaz stent was placed in the proximal stenosis, and angioplasty was performed in the distal stenosis in each of eight dogs. Two dogs were killed at 4, 8, 12, and 18 months, respectively. Specimens were studied by means of microangiography, histology, scanning electronic microscopy, and Spalteholz technique. RESULTS: At up to 12 months, there was proliferation of the vasa vasorum and a rich plexus formed in each of the animals at each treated site. More vasa vasorum were seen after stent placement than after angioplasty. The new vessels were mainly venules located in the media. At 18 months, there was regression of the venules and the vasa vasorum distribution returned to baseline. CONCLUSION: The authors conclude that the effects of stents on the vasa vasorum are temporary. PMID- 8481576 TI - Recirculation-type Amplatz clot macerator: determination of particle size and distribution. AB - PURPOSE: A high-speed mechanical clot macerator was tested in vitro, and the distributions and sizes of residual particles produced by this device were determined. MATERIALS AND METHODS: Human thrombi aged for 4 days and 10 days were macerated using a recirculation-type Amplatz thrombectomy device with an 8-F, high-speed screw propeller. The device was activated for 15, 30, and 60 seconds. Two different methods of particle measurement were used to determine overall particle distribution and to determine the size and number of large particles. RESULTS: The recirculation device liquefied 99.2% of 4-day-old and 98.8% of 10 day-old thrombi, producing particles ranging in size from 13 to 1,000 microns; all particles were smaller than 1,000 microns. Particle size and distribution results were identical for the 30-second and 60-second activation times. CONCLUSION: The recirculation-type thrombectomy device appears to perform well as a method of macerating human thrombi. Clinical trials need to be conducted to test the device further and to determine if it can be used safely on venous as well as arterial occlusions. PMID- 8481577 TI - Traumatic ischemia of the hand in a tennis player: successful treatment with urokinase. PMID- 8481578 TI - Pseudoaneurysm formation following directional atherectomy. PMID- 8481579 TI - Artifactual occlusion of the anterior tibial artery secondary to patient immobilization. PMID- 8481580 TI - Massive brachiocephalic artery bleeding due to a Gianturco tracheal stent. PMID- 8481581 TI - Resolution of diffuse vein graft narrowing after distal angioplasty. PMID- 8481582 TI - Intraperitoneal catheters: percutaneous placement with fluoroscopic guidance. AB - PURPOSE: The authors reviewed their experience with percutaneous placement of catheters into the peritoneal cavity for the administration of intraperitoneal chemotherapy to determine if their approach resulted in a lower complication rate than the reported 12%-16% rate and to demonstrate the technical advantages over surgically placed catheters. PATIENTS AND METHODS: Seventy-six patients with gastrointestinal or gynecologic malignancies underwent 152 procedures during a 20 month period. The catheters were used to deliver antineoplastic agents and, in some patients, to drain ascites. Catheter insertion was performed with local anesthesia and a modified Seldinger technique. A 5-F catheter was used in 89% of procedures; in the remainder, the catheter was of a larger caliber. RESULTS: The procedure was successful in 145 (95%) instances and failed in seven (5%) attempts because of peritoneal adhesions. The catheters remained in place for less than 2 days in 56%, 2-10 days in 25%, and more than 10 days in 19% of patients. One catheter remained in place for 15 weeks. Complications occurred in seven procedures (5%). Four cases of mild peritonitis responded to a brief course of intravenously administered antibiotics, and severe pain in two patients required premature catheter removal. A single case of inadvertent transcolonic catheter placement occurred without adverse sequelae to the patient. CONCLUSIONS: Intraperitoneal catheterization can be performed with local anesthesia by using a simple technique with a very low complication rate. The catheters can remain in place for prolonged periods without significant risks. PMID- 8481583 TI - Bleeding due to needle biopsy: effect of venopirin in an animal model and implications for humans. AB - PURPOSE: This study was undertaken to address the effect of platelet dysfunction on bleeding associated with percutaneous needle biopsy. MATERIALS AND METHODS: With use of an established animal model, 199 biopsies were performed on the livers of 13 anesthetized pigs (95 on control animals, 104 on venopirin-treated animals). The needles used were 16-22-gauge Chiba type, 18-gauge Tru-Cut, and 18 gauge Menghini. The biopsies were performed under direct vision at laparotomy with consistent technique. Blood loss was measured, and the results were compared. Statistical analysis was performed with the Student t test and the Turkey test, after logarithmic transformation of the data. RESULTS: A substantial increase in blood loss resulting from the biopsy procedures was demonstrated in the animals with platelet dysfunction. This was much greater than the effect of either needle size or prothrombin time prolongation previously reported by the authors. CONCLUSION: Platelet function may be an important factor in determining the risk of bleeding due to percutaneous needle biopsy. PMID- 8481584 TI - Percutaneous nephrostomy for nonoperative management of fungal urinary tract infections. AB - PURPOSE: Percutaneous nephrostomy has proved to be an important modality in the nonoperative treatment of bacterial pyonephrosis. The role of this technique in the management of fungal pyonephrosis continues to evolve. The authors retrospectively reviewed their experience with percutaneous nephrostomy in the management of fungal pyonephrosis. PATIENTS AND METHODS: Seven patients, two neonates and five adults, were identified with proved fungal infections. Eleven percutaneous nephrostomy tubes were placed, all with use of the Seldinger technique. RESULTS: Percutaneous nephrostomy allowed (a) prompt microbiologic diagnosis of fungal infection (Candida albicans in six patients, Torulopsis glabrata in one); (b) urinary diversion with subsequent improvement in renal function, enabling systemic administration of potentially toxic antifungal drugs 5-fluorocytosine and amphotericin B (four patients); (c) local irrigation with amphotericin B (four patients), (d) guidewire fragmentation of fungus balls (two patients); and (e) introduction of a Simpson atherectomy device to obtain biopsy specimens from an obstructing ureteral polypoid lesion (one patient). The funguria was successfully eradicated in six patients, one of whom died on the 39th hospital day of a pulmonary embolus and another of whom died of extensive small bowel infarction during hospitalization. The one patient whose outcome of antifungal treatment remains unknown died at home with a functioning percutaneous nephrostomy 23 days after the procedure. CONCLUSION: Percutaneous nephrostomy may play a role in the non-operative management of fungal urinary tract infection. PMID- 8481585 TI - Appropriateness of stent placement in the treatment of celiac artery stenosis. PMID- 8481586 TI - Prevalence and incidence of vertebral deformities. AB - There is a need to identify vertebral fractures from radiographs taken at a single point in time, but considerable controversy surrounds the methods to be used. We extended a data set to comprise baseline radiographs of the thoracic and lumbar spine on an age-stratified random sample of 762 Rochester, Minnesota, women and used revised methods to define vertebral deformities morphometrically. Changes in the method of measuring vertebral heights, changes in the source of normal values for vertebral measurements and changes in the criteria for assessing vertebral deformity had little impact on estimated prevalence and incidence in this population. The prevalence of any vertebral deformity was estimated at 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3 28.2), while the incidence of a new deformity in this group was estimated at 17.8 per 1000 person-years (95% CI, 16.0-19.7). Projected nationally, these data suggest that over 500,000 white women in the United States develop vertebral deformities for the first time each year and that over 7 million white women aged 50 years and over might be affected at any given time. These estimates are limited by the absence of a reliable 'gold standard' with which to determine false positive and false negative rates associated with this or any other morphometric method. Information on the health consequences of vertebral deformities of various sorts would be most helpful in choosing between alternative approaches to defining them. PMID- 8481587 TI - Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. AB - We evaluated the ability of bone density and vertebral fractures at baseline to predict vertebral fracture incidence in a cohort of postmenopausal women with osteoporosis. The study population was 380 postmenopausal women (mean age 65 years) treated for osteoporosis in a randomized, placebo-controlled, clinical trial of the bisphosphonate etidronate at seven geographic centers in the United States. Baseline measurements of bone mineral density were obtained in 1986 by quantitative computed tomography at the spine and dual-photon absorptiometry at the lumbar spine and hip. Vertebral fractures were documented on serial spine radiographs. Proportional hazards models were used to evaluate the ability to predict the risk of subsequent fractures during an average of 2.9 years of follow up. Presence of one or two fractures increased the rate of new vertebral fractures 7.4-fold (95% confidence interval = 1.0 to 55.9). Additional fractures at baseline further increased the fracture rate. A decrease of 2 standard deviations in spinal bone density by absorptiometry was associated with a 5.8 fold increase in fracture rate (95% confidence interval = 2.9 to 11.6). The lowest and highest quintiles of bone density had absolute fracture rates of 120 and 6 cases per 1000 patient-years, respectively. In general, the simultaneous use of two predictors (bone density and prevalent fractures or two bone density measurements) improved fracture prediction, compared with the use of a single predictor. We conclude that both bone density and prevalent vertebral fractures are strong, complementary predictors of vertebral fracture risk. The results suggest that physicians can use bone density and prevalent vertebral fractures, individually or in combination, as risk factors to identify patients at greatest risk of new fractures. PMID- 8481588 TI - Changing incidence and residual lifetime risk of common osteoporosis-related fractures. AB - Changes in incidence and lifetime risk of fractures are of major importance in the epidemiology of osteoporosis. We focused on hip fractures in women and men and on radial and humeral fractures in women. The study subjects comprised 4500 women and men 20 years old or more with fractures. In women 1735 fractures of the distal radius, 747 fractures of the proximal humerus, 878 cervical and 635 trochanteric hip fractures were included. In men 273 cervical and 232 trochanteric hip fractures were included. The fractures were registered during the period 1976 to 1984 and changes in age-specific incidence were calculated (chi-squared test for linear trend; p-values less than 0.05 were considered significant). On the basis of life tables and population background data, the lifetime risk was estimated. The incidence of cervical hip fractures in women aged 60-89 years decreased significantly (p < 0.05) during the observation period, while no significant decrease was found in the incidence of trochanteric fractures. No significant changes in incidence were observed in women with radial or humeral fractures, or in men with hip fractures. A women 60 years old with a life expectancy of 81 years had an estimated residual lifetime risk of radial, humeral or hip fracture of 17%, 8% and 14% respectively. A man 60 years of age with a life expectancy of 77 years had an estimated risk of hip fracture of 6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481589 TI - Radial and humeral fractures as predictors of subsequent hip, radial or humeral fractures in women, and their seasonal variation. AB - Hip fractures are common in elderly women, and early risk assessment of future hip fractures is relevant in relation to prevention. We studied the predictive value of radial and humeral fractures in women. The influence of weather conditions on the risk was also studied. Women aged 20-99 years with a fracture of the distal radius (n = 1162) or proximal humerus (n = 406) were followed for 0 to 9 years. The relative risk (RR) and 95% confidence limits (CL) of subsequent fracture among women suffering radial or humeral fractures compared with the background population were calculated. Women 60-79 years of age who had suffered a fracture of the distal radius or proximal humerus had relative risks of sustaining a hip fracture of 1.9 (1.3-2.6, 95% CL) and 2.5 (1.3-3.6, 95% CL) respectively. The relative risk of hip fracture was highest within the first years following a fracture of the radius or the humerus. Women suffering an upper extremity fracture (radius or humerus) in snowy or icy weather had a marginally increased risk (RR = 1.3, 0.4-2.3, 95% CL and RR = 1.8, 0.3-3.4, 95% CL) for a later hip fracture. A woman 50 years old with a radial or a humeral fracture had an estimated residual lifetime risk of sustaining a subsequent hip fracture of 17% and 16% respectively compared with 11% for the background population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481590 TI - The assessment of vertebral deformity: a method for use in population studies and clinical trials. AB - The absence of specific criteria for the definition of vertebral fracture has major implications for assessing the apparent prevalence and incidence of vertebral deformity. Also, little is known of the effect of using different criteria for new vertebral fractures in clinical studies. We therefore developed radiological criteria for vertebral fracture in women for assessing both the prevalence and the incidence of vertebral osteoporosis in population and in prospective studies and compared these with several other published methods. Normal ranges for vertebral shape were obtained from radiographs in 100 women aged 45-50 years. These included ranges for the ratios of anterior/posterior, central/posterior and posterior/predicted posterior vertebral heights from T4 to L5. The predicted posterior height was calculated from adjacent vertebrae. In contrast to other methods, our definition of fracture required the fulfillment of two criteria at each vertebral site, and was associated with a lower apparent prevalence of fracture in the control women due to a lower false positive rate. The prevalence and incidence of vertebral deformity using different criteria were then compared in a series of women with skeletal metastases from breast cancer in whom radiographs were obtained 6 months apart. The prevalence of vertebral deformity and the specificity for deformity varied markedly with differing criteria. Using a cut-off of 3 standard deviations the prevalence of vertebral deformity in the women with breast cancer was 46%. Using other methods, the prevalences of deformity ranged from 33% to 74%. Over a 6-month interval 25% of patients with breast cancer sustained 61 deformities using our method, of which only 8% resulted from errors in reproducibility. The number of patients sustaining new deformities was increased twofold when assessed by other methods (45%-53%), but errors of reproducibility may have accounted for 21% of the new deformities. The magnitude and distribution of these errors have important implications for the apparent therapeutic efficacy of agents in clinical trials of osteoporosis. The rapid semi-automated technique for assessing vertebral deformities on lateral spine radiographs that we have developed has a high specificity, and reduces the impact of errors of reproducibility on estimates of prevalence and incidence. The method should prove a value in assessing vertebral deformity both in population studies and in prospective clinical trials. PMID- 8481591 TI - Consequences of a hip fracture: a prospective study over 1 year. AB - From a population of 230,000 residents, 1429 consecutive hip fracture patients were studied with regard to their social and physical functions both before sustaining the fracture and 1 year later. Changes in the patients' accommodation, need of help and walking aids were described. Using logistic regression we found important factors regarding the ability to return home, mortality within 1 year and length of hospital stay. The cost of a hip fracture over the time a patient is in hospital is, including the cost of an internal fixation, about US $6000. The total cost over 1 year is about US $26,000 per patient, including the operation. PMID- 8481592 TI - Age-related differences in total and regional bone mass: a cross-sectional study with DXA in 429 normal women. AB - Total body bone mineral content (TBBMC), total body bone mineral density (TBBMD) and regional bone mineral content (BMC) and density (BMD) were assessed by dual energy X-ray absorptiometry (DXA) in 429 normal women aged 15-83 years, of whom 242 were premenopausal and 187 postmenopausal. The population was divided into 5 year age groups. In the premenopausal women no changes in TBBMC, TBBMD or regional BMC and BMD were observed with age, and TBBMC and TBBMD values correlated well with body weight (p < 0.001). Postmenopausal women showed an overall reduction in bone mass (p < 0.001), more marked at the axial level than peripherally (1.6% vs. 0.8%/year). The values of TBBMC and TBBMD correlated well with chronological age, time since the onset of menopause and body weight (p < 0.001). In these women age did not correlate with body weight, which suggests that postmenopausal bone mass loss depends more on chronological age and time since the onset of menopause than on other variables. The stability observed in bone mass values from ages 15-19 to menopause highlights the importance of stimulating the acquisition of an appropriate peak bone mass in women before adolescence begins. PMID- 8481593 TI - Broadband ultrasound attenuation compared with dual-energy X-ray absorptiometry in screening for postmenopausal low bone density. AB - Broadband ultrasound attenuation (BUA) was investigated as an inexpensive, simple and radiation-free method of screening for low perimenopausal bone density. A total of 587 women (50-54 years), invited for screening had bone mineral density (BMD) measured at the femoral neck and the lumbar spine by dual-energy X-ray absorptiometry (DXA). At the same visit the BUA of the calcaneus was measured. The correlation between BUA and BMD was approximately 0.4 compared with 0.67 between femoral neck and spinal BMD. Receiver operating characteristic (ROC) curve analysis demonstrated BUA to have the same ability for discriminating between low BMD at either the femoral neck or lumbar spine. BUA with a cut-off for normality at the median (BUA = 80) had a sensitivity of 68% and specificity of 67% for low bone density identified by a BMD less than the 25th centile at the femoral neck or lumbar spine. The correlation between BUA and BMD was insufficient to allow identification of the same groups as having low bone density. PMID- 8481594 TI - New bisphosphonates in osteoporosis. AB - Bisphosphonates are non-biodegradable compounds characterized by a phosphorus carbon-phosphorus bond. By substituting the hydrogens on the carbon atom, a variety of bisphosphonates can be synthesized, each with distinct physical chemical, biologic, therapeutic, and toxicologic characteristics. Bisphosphonates have in general a strong affinity to calcium phosphates, both in vitro and in vivo. They inhibit bone resorption through a cellular mechanism that is not yet completely understood. When given in large amounts, some bisphosphonates can inhibit normal and ectopic mineralization through a physical-chemical mechanism. The main difference among the various compounds appears to be their potency in inhibiting bone resorption, which can vary from 1 to 10,000. The potential efficacy of bisphosphonates in osteoporosis has been investigated extensively in animals. In the growing rat, they induce an increase in intestinal absorption and body retention of calcium. Various types of experimental osteoporosis, such as induced by immobilization, ovariectomy, administration of corticosteroids, or low calcium diet, can be prevented. Bisphosphonates are rapidly cleared from plasma, with 20%-60% deposited in bone and the remainder excreted in the urine. The half life in bone is, however, very long. The toxicity of bisphosphonates is low, probably because of their rapid plasma and soft tissue clearance. It varies greatly from compound to compound. Bisphosphonates are used successfully in diseases with increased bone turnover, such as Paget's disease of bone, tumoral bone disease, and recently, osteoporosis. Most results in osteoporosis have been obtained with etidronate and pamidronate. Both of these compounds, as well as other bisphosphonates, such as tiludronate, alendronate, and clodronate, inhibit bone loss and sometimes even increase bone mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481595 TI - Rationale for the use of clodronate in osteoporosis. AB - Bisphosphonates are widely used in disorders associated with increased resorption of bone, particularly in Paget's disease of bone and in the hypercalcemia of malignancy. Because of their undoubted efficacy and relatively low toxicity, bisphosphonates are attractive candidates for the management of osteoporosis. Clodronate, one of the many bisphosphonates being tested in osteoporosis, may be given intravenously or by mouth. In contrast to etidronate, even high doses of clodronate do not impair the mineralization of bone, making it suitable for long term use in osteoporosis. As do all the bisphosphonates tested thus far, clodronate appears to delay the rate of bone loss in osteoporosis. Long-term studies are relatively few, so that its steady-state effects on bone mass are not yet known. Most data suggest clodronate is capable at least of delaying the rate of bone loss, but several pilot studies with this agent suggest that increments of bone mass might be sustainable for several years. Clodronate is likely to decrease the frequency of osteoporotic fractures, but there is no evidence for this at present. Well-controlled, long-term prospective studies are needed. PMID- 8481596 TI - Visions for the future in osteoporosis research. AB - An ideal therapeutic agent for osteoporosis-one that both inhibits osteoclastic bone resorption and stimulates new bone formation-is not currently available. Currently available resorption inhibitors (estrogen, bisphosphonates, and calcitonin) prevent further bone loss and stabilize bone mass. However, they have a negligible to very modest effect on bone formation over prolonged periods, and do not cause prolonged increases in bone mass. A universally acceptable bone formation stimulator is not currently available. Future research is likely to focus on the use of peptide growth factors to stimulate appositional bone growth, or on the use of low molecular weight compounds that may selectively stimulate bone cells to produce these factors in the local bone remodeling microenvironment. PMID- 8481597 TI - Calcitonins: newer routes of delivery. AB - Because of its anti-osteoclastic and analgesic properties, calcitonin is a first line choice in the treatment of several bone diseases characterized by absolute or relative bone resorption. With regard to the prevention and treatment of postmenopausal osteoporosis, the chronic nature of the disease and the subsequent long duration of the pharmacological intervention require uncomfortable parenteral administration to be repeated on a long-term basis. Newer routes of administration have therefore been developed. At present the most promising of these are the nasal spray and the rectal suppository. Both routes have been shown to induce significant increases in plasma levels of salmon calcitonin. The ability of salmon calcitonin to cross the nasal mucosa was shown immunologically by the generation of specific anti-salmon-calcitonin antibodies in the plasma. In healthy volunteers these alternative routes of administration do not decrease the anti-osteoclastic activity of calcitonin, as demonstrated by a significant decrease in biochemical parameters that reflect bone turnover. In the prevention and treatment of postmenopausal osteoporosis, as well as in the treatment of Paget's disease of bone, the properties of calcitonins are generally preserved if they are administered non-parenterally. However, the equivalent doses required to sustain the effects of calcitonin have not been fully elucidated. This article reviews the potential benefits of two methods of non-parenteral administration of calcitonins in the prevention and treatment of postmenopausal osteoporosis. PMID- 8481598 TI - Criteria for successful estrogen therapy in osteoporosis. AB - Estrogens are well established as agents that stabilize the skeleton and reduce the risk of osteoporotic fractures among postmenopausal women. For maximum benefit, preventive therapy should begin as early as possible after ovarian failure begins to occur. Efforts to prevent bone loss are likely to achieve the best results when initiated prior to significant loss of bone tissue and trabecular penetration. An effect on skeletal bone mass can be obtained by any route of administration and transdermal estrogen use is an alternative to oral estrogen. Long-term therapy may reduce the risk of hip fracture by 50% and of vertebral fracture by a greater amount. The minimum effective dose is probably that which achieves circulating estrogen levels in the mid-follicular range. For women with a uterus in place, a progestin usually is provided to protect the endometrium; it is given cyclically in younger women but may be given continuously in women several years past menopause. Progestins do not interfere with the effects of estrogen on the skeleton, and it is possible that some progestins enhance the skeletal effects of estrogen. For patients with osteoporosis, estrogens can be used as first-line therapy since in these patients they have the same skeletal stabilizing effect and reduce the risk of recurrent fracture. PMID- 8481599 TI - Vertical transmission of viral hepatitis. PMID- 8481600 TI - Donor deferral registries. AB - In the last half of this century, donor deferral registries have grown in size, scope, and importance for blood collection organizations and regulatory agencies. This has occurred despite the lack of direct evidence that, when used with all other methods, they contribute meaningfully to the safety of the blood supply. Any decrease in the perceived benefit of deferral registries has been a result of the introduction of a panoply of serological testing of donor blood intended to detect transmissible disease. As the sensitivity of serological testing improves, the relative merit of the subjective methods used for blood supply safety diminish. Although computers have become a mainstay in the management of deferral registries, accurate and consistent donor identification, good manual systems, and quality control of data bases are key features to their successful management. As with the other subjective methods used in maintaining blood supply safety, techniques must be developed to determine the value of the many features of donor deferral registries. Efforts must be made to simplify these processes and focus on those elements that provide important contributions to blood supply safety. Today, donor deferral registries are major activities in most blood centers and are believed to play a significant role in blood supply safety. It is time for their role to be carefully reexamined. PMID- 8481601 TI - Leukodepletion blood filters: filter design and mechanisms of leukocyte removal. AB - Modern leukocyte removal filters have been developed after years of refinement in design. Current filters are composite filters in which synthetic microfiber material is prepared as a nonwoven web. The filter material may be surface modified to alter surface tension or charge to improve performance. The housing design promotes effective contact of blood with the filter material and decreases shear forces. The exact mechanisms by which these filters remove leukocytes from blood components are uncertain, but likely represent a combination of both physical and biological processes whose contributions to leukocyte removal are interdependent. Small-pore microfiber webs result in barrier phenomena that permit retention of individual cells and increase the total adsorptive area of the filter. Modifications in surface charge can increase or decrease cell attraction to the fibers. Optimum interfacial surface tensions between blood cells, plasma, and filter fibers not only permit effective blood flow through small fiber pores, but also facilitate cell contact with the material. Barrier retention is a common mechanism for all modern leukocyte-removal filters and applies to all leukocyte subtypes. Because barrier retention does not depend on cell viability, it is operative for cells of any age and will retain any nondeformable cell, including whole nuclei from lymphocytes or monocytes. Barrier retention is supplemented by retention by adhesion. RBCs, lymphocytes, monocytes, granulocytes, and platelets differ in their relative adhesiveness to filter fibers. Different adhesive mechanisms are used in filters designed for RBCs compared with filters designed for platelets. Although lymphocytes, monocytes, and granulocytes can adhere directly to filter fibers, the biological mechanisms underlying cell adhesion may differ for these cell types. These differences may depend on expression of cell adhesion molecules. In the case of filtration of fresh RBCs, platelet-leukocyte interaction seems to supplement other mechanisms of leukocyte retention. The interactions of cells with biomaterials is an area of important research for implantable medical devices, artificial organs, and orthopedic, vascular, and dental prosthetics. Research in these areas is likely to contribute to improved biomaterials for blood filters. Improved techniques for the preparation of hybrid polymers and new techniques for surface modification of existing polymers will increase the technical opportunities for the development of synthetic surfaces ideally designed for leukocyte removal. It is therefore likely that the performance of leukocyte-removal filters will continue to improve. The development of cost-effective leukocyte removal filters specifically designed for use during component preparation would permit leukocyte depletion of all cellular blood components. PMID- 8481602 TI - Recombinant activated factor VII in the treatment of bleeding episodes in patients with inherited and acquired bleeding disorders. AB - The FVIII/FIX by-passing agent, rFVIIa, offers an alternative approach to the treatment of hemophilia patients as well as nonhemophiliacs with antibodies against FVIII/FIX. Such treatment can be administered regardless of the inhibitor titer in these patients, and rFVIIa is active hemostatically in hemophilia B patients also. It is easy to administer but seems to need repeated dosing at 2 to 3-hour intervals, at least initially, in patients with severe bleeding, with a dose of 70 to 100 micrograms/kg body weight required to induce hemostasis. Depending on the severity of the bleeding the dose intervals may be prolonged to every 3 hours for 1 to 2 days or until clinical improvement is observed. Thereafter, the dosage interval can be increased to every 4 hours if continued therapy is required. PMID- 8481603 TI - Perfluorocarbon-based red blood cell substitutes. AB - Since our review 5 years ago, a new generation of PFC emulsion has been developed and is undergoing extensive testing. This new generation is the result of the application of physicochemical principles, applied to both the choice of the PFC itself and the emulsifier, as well as advances in emulsion-producing technology. The efficacy of PFCs in general for oxygen transporting capability has been fully recognized, as exemplified by the limited license issued to Fluosol. The latter also represents the recognition of the relative absence of major toxicity of PFCs in general. The development of new products owes much to the lessons learned during the past 20 years and to advances made in the physical chemistry of PFCs. These advances now permit the rational selection or design of the most appropriate PFC and the design of emulsifiers best suited for the purpose. Perflubron represents a clear advance over the Fluosol-DA-type formulation. It is only one but the most advanced of the second-generation products. At least three other commercial entities (Hema-Gen/PFC, Green Cross, Adamantech) are also developing products based on the above principles. Five years ago we concluded that, in spite of the enormous complexity of PFC emulsions as large volume parenterals, they have shown remarkable biocompatibility. The advances in the past 5 years have confirmed this conclusion. The advances occurring during the past 5 years show that the application of the proper technology can lead to product improvement, and that PFC preparations with significant transfusional and nontransfusional potential are, in fact, feasible. It remains to be seen whether high PFC-content emulsion can be successfully deployed in initial, prehospital resuscitation situations. The high PFC content will reduce the absolute requirement for the maintenance of FIO2 > 0.8 in the case of Fluosol-DA for optimal efficacy. The second-generation products also seem to lend themselves to intraoperative use, because they can be removed from the blood postoperatively by plasmapheresislike methods. They are also suitable in combination with autologous blood donation/transfusion. All of these potential applications are in various stages of exploration and, if found to be efficacious, will likely conserve the supply of whole blood and blood components. The nontransfusional applications, particularly those in diagnostic imaging, seem to show substantial promise. Because they involve smaller doses than transfusional applications, they may enter clinical use earlier. The applications in radiation and chemotherapy of malignant diseases represent an intermediate position between the transfusional and nontransfusional uses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481605 TI - New program established in naturopathic medicine. PMID- 8481604 TI - Challenges in transfusion microbiology. PMID- 8481606 TI - Role modeling. PMID- 8481607 TI - Nurse chooses life and accountability. PMID- 8481608 TI - The creative mind project: in search of healing. PMID- 8481609 TI - Nurses for the environment: taking a stand on current issues. PMID- 8481610 TI - Parents' and teachers' praxes of and attitudes to the health and sex education of young people with mental handicaps: a study in Stockholm and Tokyo. AB - In 1989/1990, parents and teachers of young people with mental handicaps in Stockholm (41 parents and 20 teachers) and Tokyo (106 parents and 111 teachers) were given a questionnaire about their praxes of and attitudes towards health and sex education. Results from the study indicated that, compared to parents and teachers in Tokyo, parents and teachers in Stockholm gave more information about health and sex to their 15-16-year-old young people with mental handicaps. This was especially so regarding information about HIV/AIDS. More parents and teachers in Stockholm also had positive attitudes towards sex and interpersonal relationships--not only for young people in general but also for young people with mental handicaps--compared to parents and teachers in Tokyo. Some questions of an ethical nature were found difficult to answer in both Stockholm and Tokyo. PMID- 8481611 TI - Clinical and cytogenetic survey of institutionalized mentally retarded patients with emphasis on the fragile-X syndrome. AB - A detailed clinical and cytogenetic survey for the fragile-X syndrome was undertaken on 201 institutionalized mentally retarded males with no previously recognized cause of retardation, and the causes of mental retardation were summarized from a total of 595 institutionalized male and female patients after the review of their medical records including clinical and cytogenetic data. Among the 201 males clinically and cytogenetically examined, five (2.5%) had abnormal chromosome findings with four (2%) having the fragile-X syndrome. Twelve of the males (6.0%) were diagnosed with a single gene disorder. In the present study, mental retardation was classified as possibly due to multifactorial causes when a genetic syndrome, chromosome abnormality or environmental insult was not identified, but mental retardation was present in one or more first and/or second degree relatives, but did not follow a recognizable inheritance pattern. Hence, mental retardation was recorded in other family members and may indicate possible multifactorial causes in 45 males (22.4%). An environmental insult was noted in 25 males (12.4%); unexplained birth defects in three males (1.5%); a specific condition or diagnosis identified, but cause unknown (e.g. Rubinstein-Taybi syndrome) in 10 males (5%); and no diagnosis made in the remaining 101 males (50.2%). Of all 595 patients (334 males and 261 females), including the 201 males who had undergone a detailed clinical and cytogenetic evaluation, 39 (6.6%) had abnormal chromosome findings, with Down's syndrome noted in 31 of the patients. Twenty-five patients (4.2%) were diagnosed with a single gene disorder while mental retardation was noted in other family members and may indicate possible multifactorial causes in 64 patients (10.8%). An environmental insult was noted in 170 patients (28.6%); unexplained birth defects in 17 patients (2.9%); a specific condition or diagnosis but cause unknown in 27 patients (4.5%); and no diagnosis made in 253 patients (42.5%). Clinical and cytogenetic screening of mentally retarded patients for the fragile-X syndrome and other causes of mental retardation is helpful in identifying individuals and their families who may benefit from genetic services such as counseling and treatment. This study was performed over an approximate 2 year period from 1987 to 1989. PMID- 8481612 TI - Staff turnover in ordinary housing services for people with severe or profound mental handicaps. AB - The characteristics and turnover of direct-care staff in two housing services for adults with moderate, severe or profound mental handicaps are described. Both staff groups were predominantly female with a good representation of staff aged under 30, and between 30 and 50 years. Most had prior experience in a caring capacity before taking up their current posts, but only a quarter to a third had a relevant vocational qualification. Turnover was similar in the two services, but varied considerably between settings in each. Average annual turnover ranged from 8 to 39% in one and from 5 to 48% in the other. However, most houses still had a core of long-serving staff providing continuity over time. The implications of the level of staff turnover found for management and staff training are discussed, as are the reasons for leaving given by former staff of one of the services, together with their views on job satisfaction, conditions of work, and the adequacy of management and training. PMID- 8481613 TI - Epilepsy, dementia and adaptive behaviour in Down's syndrome. AB - Widespread inquiry identified 378 adults with Down's syndrome resident in Leicestershire, England. The immediate carer of 351 of these (92.8%) was interviewed for the purpose of establishing a past history of seizures, including the age at which the seizures began. The immediate carer was also invited to provide information to enable the completion of an Adaptive Behaviour Scale (A.B.S.) rating. Individuals with a history of seizures were divided into two groups on the basis of whether or not seizures commenced prior to or after age 35 years. Two control groups of individuals with Down's syndrome, but without a history of seizures were selected. Adaptive Behaviour Scale scores for those in whom seizures commenced at a younger age were similar to those who had no recorded history of seizures. However, in those in whom seizures began in later life, scores on all domains of the A.B.S. were significantly reduced compared to both young epileptic patients and their controls. Adaptive Behaviour Scale scores for the older control group held an intermediate position, suggesting that late onset epilepsy may be a late manifestation of a dementing process. A clinical diagnosis of dementia recorded in the case records was significantly associated with the presence of late-onset epilepsy. This is supportive of the hypothesis that late-onset epilepsy in individuals with Down's syndrome is associated with Alzheimer's disease. PMID- 8481614 TI - Factors influencing the expectations of parents for their mentally retarded children. AB - In terms of treatment for cure, education, training and general information, parental expectations for their mentally retarded children are influenced by various factors such as the age and sex of the retarded child, the level of mental retardation, the education and occupation of the parents, and the socio economic status and area of living. In the present study, an attempt has been made to find out the correlation of six variables namely, age, sex, literacy, locality of living, level of retardation and duration of follow-up on the expectation of one hundred parents of mentally retarded children who attend the home-based services at the National Institute for the Mentally Handicapped, Secunderabad, India. The intercorrelation among the six independent variables and the dependent variable revealed that age of the child and duration of follow-up have a high correlation (P < 0.01), and literacy of the parents and duration of follow-up were positively correlated (P < 0.05 level). It was also found that age and duration of follow-up have a positive correlation. Further detailed multiple regression analysis was conducted and the results are discussed. PMID- 8481615 TI - Surgical treatment of corneal pathology in patients with Down's syndrome. AB - Keratoconus is a major cause of blindness in patients with Down's syndrome. A retrospective study of 30 corneal grafts for keratoconus in these patients revealed a 5-year graft survival of 67%. Postoperative trauma and/or infection was the main cause for graft failure. Conditions that should be met before the indication for corneal transplantation in a patient with Down's syndrome are formulated as a result of 15 years experience with that patient population. In appropriate cases, corneal transplantation may undoubtedly improve the quality of life in these patients. PMID- 8481616 TI - Medical and psychiatric needs of adults with a mental handicap. AB - This study describes the assessment of the medical and psychiatric needs of adults with a mental handicap recently resettled in community facilities including 'staffed houses'. No statistically significant differences were found for behaviour problems and psychiatric diagnosis prior to resettlement and one year after. However, increased use of primary care and expert psychiatric service were found following the resettlement. Clinical and service issues in relation to successful maintenance of people with mental handicap in the community are discussed. PMID- 8481617 TI - Span of apprehension in mentally retarded children: an initial investigation. AB - The present investigation is the first to apply Estes' (1965) span of apprehension task to the study of attentional functioning in mentally retarded persons. Detection accuracies of 25 children diagnosed as mildly mentally retarded and 25 non-retarded children were compared under conditions of 100-ms exposure duration, and either two, four, six or eight distractor letters. Significant main effects of subject group and distractor number were found, with no interaction. These results provide converging evidence in support of previous positions that posit a structural deficit in mentally retarded individuals with respect to centrally mediated processing. PMID- 8481618 TI - Possible Asperger's syndrome in a mentally handicapped transvestite offender. AB - A 38-year-old man with a moderate mental handicap and Asperger's syndrome is described. His transvestism and history of offending behaviour is interpreted in the light of this. PMID- 8481619 TI - Pathological jealousy and mental handicap. AB - Though widely reported in the general population, pathological jealousy has not previously been reported in an individual with a mental handicap. We describe the case of a 39-year-old man with a borderline mental handicap and an abnormal premorbid personality who demonstrates the condition. PMID- 8481621 TI - The influence of caffeine on human EEG under resting conditions and during mental loads. AB - The effect of caffeine (single oral doses of 200 mg and 400 mg) on the CNS was tested under resting conditions and while performing a concentration performance test in a placebo-controlled pilot study on ten healthy males. The EEG was evaluated quantitatively by spectral analysis with a Computer Aided Topographical ElectroEncephaloMetry system. Comparison of the averaged frequency content revealed a clear difference between the change in the functional state of the brain due to the mental arithmetics, on the one hand, and the caffeine effect, on the other. Both states of altered brain activity were reflected in a particular topographical distribution of the frequency change with respect to a frontal occipital accentuation. Comparison of the two periods of mental arithmetics in the absence or presence of caffeine showed a tendency to concentration-dependent differences from each other. Administration of 200 mg and 400 mg caffeine in the relaxed state effected the decrease in spectral power in the theta and alpha ranges. The concentration performance test without caffeine effected decreases in power in the alpha range in frontal to parietal cortex and enhanced theta power in frontal and occipital regions and the alpha power in occipital cortex. The caffeine-dependent decrease in theta power and the decrease in delta power seen under relaxation conditions after 400 mg are not observed during the concentration performance test in the presence of caffeine. PMID- 8481620 TI - Alveolar surfactant and adult respiratory distress syndrome. Pathogenetic role and therapeutic prospects. AB - The adult respiratory distress syndrome (ARDS) is characterized by extended inflammatory processes in the lung microvascular, interstitial, and alveolar compartments, resulting in vasomotor disturbances, plasma leakage, cell injury, and complex gas exchange disturbances. Abnormalities in the alveolar surfactant system have long been implicated in the pathogenetic sequelae of this life threatening syndrome. This hypothesis is supported by similarities in pulmonary failure between patients with ARDS and preterm babies with infant respiratory distress syndrome, known to be triggered primarily by lack of surfactant material. Mechanisms of surfactant alterations in ARDS include: (a) lack of surface-active compounds (phospholipids, apoproteins) due to reduced generation/release by diseased pneumocytes or to increased loss of material (this feature includes changes in the relative composition of the surfactant phospholipid and/or apoprotein profiles); (b) inhibition of surfactant function by plasma protein leakage (inhibitory potencies of different plasma proteins have been defined); (c) "incorporation" of surfactant phospholipids and apoproteins into polymerizing fibrin upon hyaline membrane formation; and (d) damage/inhibition of surfactant compounds by inflammatory mediators (proteases, oxidants, nonsurfactant lipids). Alterations in alveolar surfactant function may well contribute to a variety of pathophysiological key events encountered in ARDS. These include decrease in compliance, ventilation-perfusion mismatch including shunt flow due to altered gas flow distribution (atelectasis, partial alveolar collapse, small airway collapse), and lung edema formation. Moreover, more speculative at the present time, surfactant abnormalities may add to a reduction in alveolar host defense competence and an upregulation of inflammatory events under conditions of ARDS. Persistent atelectasis of surfactant-deficient and in particular fibrin-loaded alveoli may represent a key event to trigger fibroblast proliferation and fibrosis in late ARDS ("collapse induration"). Overall, the presently available data on surfactant abnormalities in ARDS lend credit to therapeutic trials with transbronchial surfactant administration. In addition to the classical goals of replacement therapy defined for preterm infants (rapid improvement in lung compliance and gas exchange), this approach will have to consider its impact on host defense competence and inflammatory and proliferative processes when applied in adults with respiratory failure. PMID- 8481622 TI - Does pertussis infection induce manifestation of allergy? AB - To evaluate whether pertussis induces the development of allergy, a prospective study was performed in 25 children aged 0.8-12.2 years. The patients underwent allergy diagnostics during pertussis infection and at a follow-up visit 8-14 months later. Diagnostic criteria included the medical history of the patients and their families, a modified skin prick test, measurement of serum IgE and radio-allergosorbent test screening for specific sensitizations. At the time of pertussis, serum IgE concentration in the study group was 62 +/- 30 kU/ml. At the follow-up visit, there was a significant increase in serum IgE to 137 +/- 51 kU/ml, which was also significantly higher than IgE in an age-matched control group. Children at a significantly higher risk for developing IgE increase or new allergic sensitizations were those with a family history of allergy or potentially allergic disease in their personal history. Our results indicate that pertussis may induce IgE production in affected children. PMID- 8481623 TI - Clinical meaning of the torque between stance leg and ground for the analysis of gait mechanism. AB - Transversal torque between the stance leg and the ground was measured in 169 test persons with normal gait (91 women, 78 men; ages 15-79 years) using three dimensional force plates. Taking the average of six to ten single steps produces reproducible person- and group-specific data. This permits the isolation and study of individual solutions to specific problems of locomotion, so-called gait mechanisms. The relatively great torque during the double-stance phase is caused mainly by the medially directed, short-term impact peak at heel strike, with the stride length as lever arm. Double-stance torque is therefore determined by motion dynamics and does not help in understanding individual gait mechanisms. Torque measured during the single-stance phase is, in comparison, rather small and is interindividually relatively variable. Experimentally measured torque is considered in terms of various hypotheses concerning the creation of torque in the human gait. Men obviously tend, for reasons of equilibrium and stability, to compensate the various torques. Better than the more known vertical, sagittal, and frontal force components, the remaining torque represents the individual problem solution and therefore permits the study of specific gait mechanisms, both physiological and pathological. Using the characteristic gait of patients with hemiplegia as an example, it is shown that pathological torque observed systematically on the nonaffected side in such patients is a quantitative measure of the trunk rotation necessary to move the plegic side forward. Measurement of this torque therefore permits precise determination of the degree of damage, as well as quantitative control and objective documentation of the rehabilitation progress. PMID- 8481624 TI - HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors. AB - The prevalence of circulating autoantibodies against thyroperoxidase (mic-TPO) was determined in 3,000 healthy blood donors (age range: 23 to 60 years) from the Hamburg area. Of the blood donors, 153 (5.1%) were found to have high titer of mic-TPO (> 350 IU/ml). Only two autoantibody positive subjects (0.06%) were chemically hyper- and hypothyroid, respectively. Analysis of HLA-DR specificities revealed that HLA-DR specificities DR3 and DR5 were significantly increased when compared to controls (n = 1,863). Comparison of the autoantibody-positive probands with a group of disease controls, i.e., Graves' patients and patients with lymphocytic thyroiditis, revealed a higher prevalence of HLA-DR3-positive HLA haplotypes in the disease controls when compared to autoantibody positives. Individuals with a mic-TPO level greater than 2,000 IU/ml were almost exclusively found to have one HLA-DR3 or HLA-DR5 positive HLA haplotype. We conclude that a high prevalence of high-titer mic-TPO can be found in healthy blood donors. Circulating signs of thyroid autoimmunity were associated with HLA specificities also found to be associated with autoimmune thyroid diseases. PMID- 8481625 TI - Clinical application of three-dimensional sonography in internal medicine. AB - Three-dimensional sonography represents a development of non-invasive diagnostic imaging by real-time two-dimensional sonography. The use of transparent rotating scans, comparable to a block of glass, generates a three-dimensional effect. The first clinical application of this technique was in the field of gynecology and obstetrics, namely in prenatal diagnostics. In this study we describe its first application in internal medicine. In preliminary examinations on healthy volunteers we obtained specific processing data for optimal imaging results. This was followed by secondary examinations on 123 patients who had previously undergone conventional sonography with pathological findings. In more than 75% of the cases examined we found an optimal reproduction of sonographic findings with respect to the evaluation criteria developed by us for the three dimensional imaging of processed data. With the inclusion of measurement parameters such as distance determination and volume measurements the data gathered will allow the generation of reproducible results. Future studies will confirm the value of this method in diagnostic imaging. PMID- 8481626 TI - Xanthoma disseminatum: a rare normolipemic xanthomatosis. AB - Xanthoma disseminatum (XD) is a rare benign histiocytic disorder with extensive cutaneous and mucous membrane xanthomas in normolipemic patients. We describe the 9-year course of a 25-year-old white man who presented with multiple brownish reddish papulous skin tumors that developed over 3 years and remained relatively constant, with spontaneous regression and progression of individual lesions since. In addition, there was asymptomatic xanthomatous infiltration of the epipharnyx and symptomatic infiltration of the synovial membrane of the left knee joint leading to restriction of movement. Histologically, the corium was infiltrated by large lipid-storing macrophages, polynucleated histiocytic giant cells of the Touton and the foreign body type. Immunhistochemically, the lipid storing cells could be classified as macrophage/monocyte derived cells distinctly different from Langerhans' cells without proliferative activity. The clinical picture and course as well as laboratory findings indicating normolipidemia made it possible to differentiate XD from other normolipemic xanthomatosis, especially juvenile xanthogranuloma, eruptive histiocytoma, and histiocytosis X. The etiology of XD is still unknown. It is possible to differentiate xanthoma disseminatum from malignant histiocytosis X by the clinical picture and immunhistochemical studies. Thus it is no longer justified to administer cytostatic treatment for this disorder. PMID- 8481627 TI - Serum CA 125 levels in patients with non-malignant liver diseases without ascites. PMID- 8481628 TI - Bioequivalence of allopurinol preparations: to be assessed by the parent drug or the active metabolite? AB - Allopurinol is converted almost completely into a single active metabolite, oxipurinol, which has the same therapeutic pattern but a much longer elimination half-life than the parent compound. Therefore both allopurinol and oxipurinol were evaluated in our bioequivalence study in healthy volunteers comparing two allopurinol brands. Bioequivalence determination was based on the 90% confidence intervals (CI) of the area under the plasma concentration time curve from time zero to infinity (AUC0-infinity), of the area from time zero to the last measurable plasma concentration (AUC0-t (last)), and Cmax. Because of the lack of compound-specific criteria we used conventional limits for the bioequivalence range. Under these conditions the brand chosen as test preparation was judged to be bioequivalent to the reference form with respect to the extent of bioavailability, AUC0-infinity, and AUC0-t (last) of the parent drug. The CI of Cmax of allopurinol slightly exceeded the upper limit of 130%, so that bioequivalence was not confirmed with regard to the rate of bioavailability of the parent compound. The CI values of both AUC and Cmax of the active metabolite were tighter than those of allopurinol. In addition, the CI values of Cmax of oxipurinol were smaller than those of the corresponding AUC. As a consequence the test drug can clearly be accepted as bioequivalent, based on metabolite data. Since the active metabolite is of greater therapeutic significance than the parent drug, assessment of the bioequivalence of allopurinol preparations needs to be based on oxipurinol rather than allopurinol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481629 TI - Heterozygotic gene expression in endomyocardial biopsies: a new diagnostic tool confirms the Duchenne carrier status. AB - Identification of the defective gene and the absent gene product dystrophin can substantiate the clinical evidence for manifesting X-linked Duchenne type muscular dystrophy (DMD). It is not always possible, however, to rule out definitely a clinically asymptomatic carrier status in question, since even in the proven carrier DNA analysis is often inconclusive, and multinucleated skeletal muscle fibers express a basically normal membrane dystrophin. To substantiate the value of endomyocardial biopsy as a new tool for detection of the DMD carrier status we examined an endomyocardial biopsy of a volunteer who met the clinical criteria of a DMD carrier. Dystrophin immunohistochemistry and western blot of her skeletal muscle biopsy were inconclusive, and polymerase chain reaction and cDNA analysis failed to locate directly the X-chromosomal defect. We observed a clearcut mosaic of dystrophin-positive and -negative mononucleated cardiac muscle cells, reflecting a heterozygote carrier status in her endomyocardial biopsy, whereas 20 controls were uniformely positive. The incidence of DMD (1:3000 males) and especially the 30% spontaneous mutation rate, still the major pitfall in DNA analysis, show the need for an additional diagnostic tool. PMID- 8481630 TI - Diets, lipids, calcium and hypertension. PMID- 8481631 TI - Who has the right to end life? PMID- 8481632 TI - Laws needed to control gene therapy. PMID- 8481633 TI - Preoperative information: the role of the ward nurse. AB - Many health care professionals are becoming increasingly aware of the benefits of giving preoperative information to patients. However, many nurses still view the provision of such information as a luxury, only to be afforded when all the 'proper' work is done. PMID- 8481634 TI - Holism in nursing: its meaning and value. AB - The term holism implies the integration of parts to achieve harmony. What can this ideal mean in a world which is fragmented and in a nursing context constrained by resources? Holism has some valuable applications for nursing and some warnings too. PMID- 8481635 TI - Child sexual abuse. 2: Techniques for helping adult survivors. AB - Nurses play a valuable role in helping victims of child sexual abuse. Through constant reassurance and skilled assistance the victims can realize that they can survive the abuse experience. The nurse wishing to work with this group of patients has an ethical and moral obligation to develop the necessary expertise and clinical competence to ensure that the intervention does not cause further harm and the development of maladaptive behaviour. PMID- 8481636 TI - Quality of life after intensive care. AB - Quality of life must be assessed after patients have received intensive care. Long-term survival of intensive care patients should be evaluated. TISS (Therapeutic Intervention Scoring System) is an extremely useful tool for estimating the cost of treatment given to an individual patient. APACHE II (Acute Physiology and Chronic Health Evaluation) is an effective index for measuring severity of illness. Age of patient and severity of illness dramatically affect the cost of treatment in intensive care. PMID- 8481637 TI - Do the benefits of continuing education outweigh the costs? AB - Debate on the costs and benefits of continuing professional education for nurses has intensified following the PREPP proposals. Evidence suggests that nurses who consider that their educational needs are being fully met have higher morale and work more efficiently than those who do not. PMID- 8481638 TI - Distance learning. AB - South Bank University boasts the only Diploma in Professional Studies in Nursing course in the UK that can be undertaken entirely by distance learning. How does it work and what should students hope to gain from such a course? PMID- 8481639 TI - In remembrance of nursing pioneers: Tiffany, Wells and Jones. PMID- 8481640 TI - The professional role of the nurse. AB - The extent to which nurses feel that their contribution is recognized and that they are involved in important decisions varies according to grade and location. Clinical nurses generally feel that they exert little influence over doctors, general management or their own nurse managers. PMID- 8481641 TI - Neurological emergencies. 2: Nurse-aid management of fits. AB - During the fit, the patient should be protected from further injury. The nurse aider should remove or guard the patient against dangerous objects nearby. To avoid further injury the nurse aider must carefully restrain and control the patient's movements. A clear airway must be maintained. The patient should be placed in the recovery position. Details of the fit should be observed. PMID- 8481642 TI - How to promote quality of care and preserve patient autonomy. AB - This article explores the relationship between the provision of a quality service and the promotion of patient autonomy. The key issue of meeting patients' actual needs while maintaining their self-worth within a budget-conscious environment is examined. PMID- 8481644 TI - Home is where the debts are. PMID- 8481643 TI - Impediments to advanced practice nursing. PMID- 8481645 TI - Live to work, work to live? PMID- 8481646 TI - Camp nursing: tips to help you experience success. PMID- 8481647 TI - Help! She's in labor! PMID- 8481648 TI - Show the $value$ of nursing. PMID- 8481649 TI - Pathogenic significance and diagnostic value of lupus autoantibodies. AB - Systemic lupus erythematosus (SLE) is characterized by a panoply of autoantibodies (more than 50). Some of them are more prevalent (anti-ds DNA > 80%) while others are less frequently detected, but highly specific for SLE (anti Sm, 20%). In this review we will discuss the clinical significance of anti-RNP, anti-Ro, anti-La and anti-phospholipid antibodies. We will also summarize the clinical and experimental evidence for the pathogenic role attributed to each one of these antibodies. PMID- 8481650 TI - Iris protein antibodies in serum of patients with juvenile rheumatoid arthritis and uveitis. AB - Homogenates of bovine iris were fractionated by gel filtration chromatography, and the column-eluted proteins were probed with pooled sera obtained from patients with pauciarticular juvenile rheumatoid arthritis (JRA). The serum pool prepared from patients with pauciarticular JRA and a history of anterior uveitis, but not from those without the eye disease, contained IgG antibodies which bound a low molecular weight iris antigen (LMW-IA) as measured by a modified ELISA. LMW IA was protease-sensitive and contained at least four proteins of approximate molecular weights of 16, 13, 9 and 6.5 kD with no uronic acid or carbohydrate. Analysis of individual patient sera for IgG anti-LMW-IA antibody demonstrated that 1/20 (5%) pediatric non-rheumatic disease controls (NRDC), 1/19 (5.3%) non uveitic pauciarticular JRA patients and 6/21 (28.6%) uveitic pauciarticular JRA patients were positive by ELISA. Levels of anti-LMW-IA antibody did not correlate with serum IgG concentration, the presence of IgG antibody to soluble retinal S antigen (S antigen) or reactivity to the low molecular weight fraction of bovine choroid (LMW-C). Ten of 21 (47.6%) children with pauciarticular JRA and uveitis had serum antibody that reacted with LMW-IA and/or retinal S antigen as compared to 1/20 (5%) NRDC patients and 3/19 (15.8%) patients with pauciarticular JRA uncomplicated by uveitis. Analysis of patient immunoreactivity to proteins of the anterior uveal tract may provide a greater understanding of pathogenic features related to arthritis-associated eye disease. PMID- 8481651 TI - Use of a high molecular weight Entamoeba histolytica antigen fraction in enzyme linked immunosorbent assay and thin layer immunoassay tests. AB - A high molecular weight Entamoeba histolytica antigen fraction I was employed for the determination of anti-amoebic antibodies in ELISA and thin layer immunoassay (TIA) tests. A large number of human serum and immunized guinea pig serum samples were tested against this antigen. In comparison, ELISA was found more sensitive than the TIA technique. The potent antigen fraction I used in these tests was lyophilized at an optimum concentration of 1 mg/ml for obtaining uniform results. PMID- 8481652 TI - Expression of the alpha chain of human Fc epsilon RI in transfected rat basophilic leukemia cells: functional activation after sensitization with human mite-specific IgE. AB - The actual dilemma in studying the binding and triggering capacity of IgE from allergic patients is the lack of cultured basophils or mast cell analogs of human origin. Human IgE binds with exquisite species specificity to the high affinity IgE receptor (Fc epsilon RI) expressed on the surface of these cells. In rodents this receptor has been characterized as a tetrameric plasma membrane protein composed of an IgE-binding alpha chain, a beta chain and two disulfide-linked gamma chains. In order to establish a cell line expressing the alpha chain of human Fc epsilon RI which can be triggered with IgE from human patients and specific allergen, we transfected the cDNA coding for the human alpha subunit into rat basophilic leukemia cells. The resulting transfectants express the human alpha chain on the cell surface in the form of a hybrid complex associated with endogenous rat gamma chains. After sensitization with human IgE from mite specific patients, the transfectant produces a calcium response upon incubation with allergen. The established cell line can be used as a model system to study the mechanism of mast cell triggering through IgE from allergic patients. PMID- 8481653 TI - Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythematosus. AB - Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 +/- 11 and 25 +/- 11 mm Hg, respectively. However, the frequency of PH was higher in SLE (60%) than in MCTD patients (33%). The titers of aCL were significantly higher in SLE (38 +/- 27 IU/ml) than in MCTD (17 +/- 7 IU/ml; p < 0.02). Two SLE patients with high titers of aCL had multiple cerebral infarction and transverse myelitis, and deep vein thrombosis, respectively. A significant correlation between the titers of aCL and mPAP was observed in patients with MCTD (p < 0.05), but not in patients with SLE. PMID- 8481654 TI - Relationship among asthma, serum IgE levels and skin test sensitivity to inhaled allergens. AB - In two groups of subjects, we have shown that increased high total serum IgE levels (with and without age and sex correction) are significantly associated with the asthmatic phenotype, as diagnosed by a physician. This association was confirmed by discriminant analyses; as compared to variables such as specific sensitivity to allergens and smoking history, age- and sex-corrected log[total serum IgE] was the best predictor of the status of physician-diagnosed asthma in these subjects. Additionally, we observed significantly increased skin test sensitivity to house dust allergens in asthmatics. These findings support previous studies showing that high total serum IgE levels and IgE-mediated sensitivity to house dust allergens are associated with the presence of asthma. PMID- 8481655 TI - Late phase bronchoconstriction and eosinophilia as well as methacholine hyperresponsiveness in Ascaris-sensitive rhesus monkeys were reversed by oral administration of U-83836E. AB - We used the Ascaris-sensitive primate model to assess the effect of oral doses of the 2-aminochroman (U-83836E) lazaroid on the antigen-induced late phase (24 h) bronchoconstriction (LPBC), eosinophilia and methacholine hyperreactivity. Following establishment of consistent lung resistance measurements and bronchoalveolar lavage eosinophilia in 4 Ascaris reactor primates, we determined the baseline aerosol mecholyl provocative challenge for 50% increase (PC50 in mg/ml) in these animals. Twenty-four hours following antigen challenge, we again determined the PC50 (mg/ml). In all 4 animals, there was a statistically significant decrease in PC50 (5.4- to 32-fold, n = 5-7; p < 0.029). Bronchoconstriction at 24 h increased in all 4 (49-86% over saline aerosol, p < 0.05). Eosinophilia increased from 21 to an average of 33% of total cells (p < 0.05 compared to saline). Repeating the antigen challenge in the presence of oral doses of 10 mg/kg U-83836E 18 and 3 h before and 6 h after challenge resulted in 53-70% inhibition of LPBC, 53-81% inhibition of eosinophilia (p < 0.05 compared to Ascaris) and return of the mecholyl PC50 (mg/ml) to before antigen levels (p = NS) thus blocking increased hyperreactivity. These results indicate U-83836E, like steroids, would be an effective drug for asthma and lung inflammation. PMID- 8481656 TI - Immunosuppressive factors detected during convalescence in a patient with severe serum sickness induced by carbamazepine. AB - We report on a patient with severe serum sickness induced by carbamazepine in whom anticarbamazepine IgG antibodies were detected in the serum. The T cells of the patient showed impairment of phytohemagglutinin-induced proliferation, and hypergammaglobulinemia was evident. The clinical features and immunological abnormalities were compatible with immunoblastic lymphadenopathy. Immunosuppressive factors were also detected in the patient. Their molecular weights ranged from 20,000 to 30,000 as evaluated by Sephadex G-200 gel filtration. Such immunosuppressive cytokines were not detected in other patients with carbamazepine allergy who did not develop the clinical manifestations of immunoblastic lymphadenopathy. These results suggest that the T cell functional deficiency of immunoblastic lymphadenopathy is induced by these immunosuppressive cytokines. PMID- 8481657 TI - Lymphoma ...the next questions. Proceedings of a meeting. Orlando, Florida, April 1-4, 1992. PMID- 8481658 TI - Is the working formulation adequate for the classification of the low grade lymphomas? PMID- 8481659 TI - Bone marrow transplantation for Hodgkin's disease--recent advances and current issues. PMID- 8481660 TI - Biochemical modulation of arabinosylcytosine for therapy of leukemias. AB - Analysis of different ribonucleotide reductase inhibitors to modulate arabinosylcytosine (ara-C) metabolism suggested that pretreatment with arabinosyl 2-fluoroadenine (F-ara-A) significantly potentiated the rate of ara-CTP (5' triphosphate of ara-C) accumulation in both quiescent lymphocytes (p = 0.046) and in cycling blasts (p = 0.017). In vitro incubations of freshly isolated leukemia cells from patients with chronic (n = 7) or acute (n = 5) leukemias with F-ara-A, increased the rate of ara-CTP accumulation by a median of 1.5 or 1.7-fold, respectively, when subsequently incubated with ara-C. The objective of the present investigation was to test the hypothesis that ara-C can be biochemically modulated during therapy of leukemias. To test the biochemical modulation of ara C in the clinical setting, we designed two protocols to administer fludarabine (clinical formulation of F-ara-A) and ara-C in a pharmacologically directed sequence for patients with chronic lymphocytic leukemia (CLL) refractory to conventional fludarabine therapy or for patients with acute myelogenous leukemia (AML) in relapse. Comparison of ara-CTP pharmacokinetics demonstrated a significant increase in the area under concentration curve (AUC) of ara-CTP both in CLL (median 1.5-fold) and AML cells (median 1.8-fold) after fludarabine infusion. Analyses of different processes involved in the metabolism of ara-CTP indicated that the increase in AUC was due to potentiation of the rate of ara-CTP accumulation. These studies demonstrate that protocols designed on biochemical and pharmacological rationales modulate ara-C metabolism during therapies. PMID- 8481661 TI - Treatment of relapsed or refractory AML with intermediate-dose arabinosylcytosine (ara-C): confirmation of the importance of ara-C triphosphate formation in mediating response to ara-C. PMID- 8481662 TI - High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: results of an age adjusted randomized comparison. AB - 193 patients with relapsed or refractory acute myeloid leukemia (AML) were entered into a prospective randomized comparison of high-dose versus intermediate dose cytosine arabinoside (AraC) both combined with mitoxantrone (mitox) according to the previously established sequential HD-AraC/mitox regimen (S-HAM). AraC was administered by 3 hr inf. q 12 hrs on days 1, 2, and 8, 9 at randomly assigned doses of either 3.0 versus 1.0 g/m2 in pts. < 60 years of age or 1.0 versus 0.5 g/m2 in older pts. Mitox was given to all cases at a dose of 10 mg/m2/d on days 3, 4, and 10, 11. Randomization was stratified for primary refractoriness against induction therapy and the length of first remission in relapsed cases (< 6 mths., 6-18 mths., > 18 mths.). From 151 presently evaluable cases 72 pts (48%) achieved a complete remission (CR), 38 cases (25%) were non responders (NR) and 41 pts. (27%) died within the first 6 weeks after the start of treatment (early death = ED). No significant differences were found in CR rates being 52% and 44% for the 3.0 versus 1.0 g/m2 AraC regimens in pts. < 60 years and 48% and 45% after 1.0 versus 0.5 g/m2 AraC in older pts. No differences between the respective regimens emerged either for the time to CR (median 46 days) nor remission duration (median 4.5 mths). Analysis of treatment failures, however, demonstrated a significantly higher rate of NR after the lower dose regimens in both age groups of 41% and 32% versus 11% and 14% in pts. receiving AraC at higher doses (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481663 TI - Asparaginase revisited. PMID- 8481664 TI - Can the polymerase chain reaction be used to direct therapy? PMID- 8481665 TI - L-asparaginase and PEG asparaginase--past, present, and future. AB - L-asparaginase is an enzyme which hydrolyses asparagine. Since the 1960s it has been known that some leukemic cells are deficient in asparagine synthetase and therefore cannot manufacture sufficient quantities of this essential amino acid to maintain cell viability. L-asparaginase is predominantly useful in acute lymphocytic leukemia (ALL) although responses have been noted in patients with acute myeloid leukemia, lymphoma, and rarely other tumors. L-asparaginase has been used in conjunction with methotrexate and ara-C in combination programs in leukemia. The major side-effect limiting the usefulness of L-asparaginase is allergic reactions. In addition, it is probable that neutralizing antibodies develop which shorten the half life of the drug so that the goal of depletion of plasma levels of asparagine cannot be attained or maintained. Polyethylene glycol (M.W. 5000) can be conjugated to L-asparaginase at sites not involving the active site of the enzyme. This enables free access of a small molecule, asparagine, to the active site of the enzyme but prevents uptake by the reticuloendothelial system, greatly decreasing the probability of developing antibodies against the asparaginase and prolongs the circulating half life of the drug. In a phase I/II study conducted at the M.D. Anderson Cancer Center, 37 heavily pretreated patients with refractory hematologic malignancy were treated. The age range from 15 to 73 years, median 49 years. Nineteen patients had ALL, 15 lymphoma, two myeloma, and one Hodgkin's disease. The dose levels of PEG L-asparaginase varied from 250 IU/m2 up to 8000 IU/m2. The pharmacokinetic profile demonstrated a monophasic half life consistent with a one compartment model with a single elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481666 TI - The role of interferon in the therapy of low grade lymphoma. PMID- 8481667 TI - Combination chemotherapy in the treatment of follicular low-grade lymphoma. AB - The therapeutic approach to patients with follicular low-grade non-Hodgkin's lymphoma is controversial and has varied over a wide spectrum. A "watch and wait" approach in asymptomatic patients has been taken in some studies. In other series, single agent therapy with alkylating agents as cyclophosphamide or chlorambucil has been employed. Response rates including complete responses are high, but relapses inevitably occur. Three-drug combination chemotherapy regimens consisting of cyclophosphamide, vincristine, and prednisone (CVP) have been utilized, in addition to more intensive regimens consisting of four or more drugs. Although responses are commonly achieved, there is no consistent survival advantage conferred by these more aggressive regimens. However, the remission duration may be prolonged in some subsets of patients as those with follicular mixed lymphoma. Due to the prolonged natural history of follicular low-grade lymphoma, a long period of follow-up is necessary to adequately evaluate the impact of a therapeutic regimen on remission duration and overall survival. Future trials may employ more aggressive therapy in combination with growth factors or biologic response modifiers in an effort to improve the outcome of patients with follicular low-grade lymphoma. PMID- 8481668 TI - Treatment of low grade non-Hodgkin's lymphomas with fludarabine. PMID- 8481669 TI - Anthracycline containing regimens in intermediate grade lymphoma. Italian Cooperative Study Group on Intermediate Grade Malignant Lymphoma. AB - From March 1991 to April 1992, 44 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma (according to the Kiel classification) were entered in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the combination chemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Forty-four patients were randomly assigned to receive either CI(idarubicin)OP or CH(doxorubicin)OP. The study is ongoing and so far no significant differences in complete response rate and (non )hematologic toxicity have been observed. PMID- 8481670 TI - Human B cell lymphomas: in vitro and in vivo studies on growth factors and cell growth. AB - The B cell non-Hodgkin's lymphomas (NHL-B) are a common, but heterogeneous group of human lymphoid neoplasms, consisting of monoclonal populations of neoplastic B lymphocytes demonstrating non-random chromosomal abnormalities, often associated with proto-oncogene translocations. Clinically and pathologically, these lymphomas are classified as low, intermediate, or high grade, according to the clinical aggressiveness of the NHL-B subtype. The clinical behavior can also be correlated with biological function regarding proliferative capabilities of the tumor cells. Our studies have shown that the low grade B cell lymphomas have low constitutive proliferative capacity in vitro and do not respond to cytokine growth factors (CGF), while the high grade NHL-B respond to the B cell growth factor (BCGF) family of CGFs. The high grade NHL-B also secrete BCGFs both in vitro and in vivo, as autocrine growth factors that may provide a target for new therapeutic approaches to therapy. PMID- 8481671 TI - Prognostic factors in large-cell lymphomas. AB - A review of the most significant prognostic factors found in large cell lymphomas is presented. Prognostic factors are divided in four categories: (a) those related to the patient: age at diagnosis; (b) those related to the tumor: stage, tumor bulk, spreading of tumor, extranodal sites, LDH and beta 2-microglobulin levels; (c) those related to the host-tumor relationship: performance status, presence of B symptoms, serum albumin level, and interleukin secretion; and (d) those related to the physicians: type of treatment, dose intensity of this treatment. Most of these parameters are related to each others and only a few of them keep statistically significant correlation with outcome in multiparametric studies. New prospective studies with new therapeutic strategies should stratify patients before treatment on these most important prognostic factors. PMID- 8481672 TI - What is the role of third generation regimens for initial therapy of non Hodgkin's lymphomas? AB - The advances in therapy for aggressive non-Hodgkin's lymphoma have improved the long-term outlook for patients with this disease. However, many questions still remain such as: which combination chemotherapy protocol is the best? Is it necessary to use a third generation regimen, or is CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) adequate? And finally is the extent of dose intensity that can be achieved with conventional therapy adequate in poor prognosis patients? Although several smaller comparative trials have been done, the four arm trial currently being performed by the South West Oncology Group (SWOG) will represent the largest trial designed to address this issue. One best protocol has not yet been identified as being superior to others for the therapy of patients with aggressive non-Hodgkin's lymphomas. However, certain subsets of patients may benefit from specific protocols. This information can hopefully be gleaned from subset analysis of the SWOG study in the future. At the present time, since one best therapy cannot be identified, physicians should chose a regimen that they are confident in and familiar with it's use. By utilizing a particular regimen, one can minimize the treatment-related mortality and optimize the patient's change for a good outcome. Subset analysis to identify particular groups that may benefit from higher dose intensity will be an important feature for future analysis. PMID- 8481673 TI - Chronic administration of etoposide in the treatment of non-Hodgkin's lymphoma. AB - The importance of schedule in the cytotoxic efficacy of etoposide is suggested by the mechanism of action and supported by clinical data in the treatment of small cell lung cancer. To further evaluate the effects of drug schedule, we studied the efficacy of oral etoposide 50 mg/m2 daily for 21 consecutive days, repeated every 28-35 days, in the treatment of refractory lymphoma. Twenty-five patients were treated; all had received previous chemotherapy and were considered incurable. Fifteen patients (60%) responded to treatment (14 partial responses, 1 complete response), including 5 of 9 patients who had received previous intravenous etoposide. Median response duration was 8 months in patients with low grade lymphoma and 3 months in those with intermediate or high grade lymphoma. The single complete responder remains disease-free 19 months after completion of therapy. Two patients responded to chronic oral etoposide immediately after progression on intravenous etoposide-containing regimens, demonstrating improved efficacy of the chronic schedule. Single agent etoposide, administered at this dose for 21 days, provides an effective and convenient treatment option for patients with indolent lymphoma. Incorporation of this etoposide schedule into combination regimens for aggressive lymphoma is currently under investigation, and preliminary results are reported. We are currently conducting a phase I study using low dose, continuous infusion etoposide (25 mg/m2/day). By avoiding high peak serum levels and maintaining a constant serum level of approximately 1 microgram/ml, we hope to retain efficacy and minimize or avoid myelotoxicity. Continuous infusion was continued for as long as tolerated. Blood counts were measured weekly, and therapy temporarily interrupted if WBC < 2000/microL developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481674 TI - Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma. AB - Idarubicin, a new analogue of daunorubicin, was administered intravenously at a dose of 15 mg/m2 to 31 patients with previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age 69 years, performance status 1, and prior chemotherapeutic regimens 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 CR and 10 PR) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with non-hematologic toxicities (nausea/vomiting, mucositis, and anorexia) seen in < 50% of patients. Median hematologic values during the first cycle for this dosage included WBC 1300/mm3, platelets 129,000/mm3, and hemoglobin 10.9 mg/dl. With dose escalation, hematologic toxicity was dose-limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in intravenous form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma. Further studies employing idarubicin in non Hodgkin's lymphoma should be considered. Cardiac function should be followed in trials utilizing anthracycline-type chemotherapeutic agents. PMID- 8481675 TI - Can we identify patients with low grade lymphoma for frontline ABMT? AB - Autologous Bone Marrow Transplant (ABMT), at this point, is an experimental procedure reserved for patients without cure potential with available conventional chemotherapy. Unfortunately, the Ann Arbor staging system has not been able to identify these cases since there are patients with Stage IV who do well and others who do not. We have reported on a risk model based on gender and tumor burden (TB) assessment that can stratify patients with uniform Ann Arbor stage IV follicular low-grade lymphoma (FLGL) into three prognostic groups: (a) a group of females with low TB who have achieved a plateau of failure free survival (FFS) and survival of 50% and 92%, respectively, and who should not receive frontline ABMT; (b) a group of males with high TB having a median FFS and survival of only 12 and 48 months, respectively, and who could potentially benefit from ABMT; (c) a large group of patients with other TB-sex combinations, who are continuously relapsing at ten year follow-up, and whose survival is dismal. Even some of these, who have at best a 50% ten year survival, have not reached a plateau in their survival curves. This large group of patients, like all stage IV patients, will have a median age of 60 years at the time of initial diagnosis and treatment, and will be probably over 60 years old by the time they relapse, at which time salvage therapy will have increased morbidity and mortality, more so if it includes ABMT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481676 TI - Who are clinicians? PMID- 8481677 TI - "The significance of pain in children's experiences of hemophilia". PMID- 8481678 TI - Community elders: prevalence and correlates of depressive symptoms. AB - This pilot study examined the prevalence and correlates of depressive symptoms among community-dwelling elders 75 years of age and older. Forty subjects were recruited from a research volunteer pool. Cross-sectional data were collected during structured in-home interviews. High depressive symptoms were reported by 10 (25%) of the elders; of these, 8 were males. Depressive symptoms were positively related to the need for instrumental support. Higher depressive symptoms were associated with poorer functional health status and self-rated health and with lower morale, life satisfaction, and quality of life. Nurses working with community-dwelling elders 75 years of age or older should be alert for depressive symptoms among those with indications of poor physical and functional health, and instrumental support needs should be assessed. Further investigation into the age/gender issue as it relates to the development of depressive symptoms is warranted. PMID- 8481679 TI - Symptoms reported by older and middle-aged adults after coronary bypass surgery. AB - Knowledge of the most prevalent symptoms after coronary artery bypass surgery (CABS) can be used to assist patients to anticipate recovery. The purposes of this study were to describe the prevalence of symptoms during the first 6 weeks after CABS, to assess changes in the number and types of symptoms, and to compare symptoms in older and middle-aged adults. The most prevalent symptoms during hospitalization (Time 1) were pain, edema, wound drainage, fever, and fatigue. In the third through fifth postoperative weeks (Time 2), the most prevalent symptoms were pain, edema, sleep problems, fatigue, and wound drainage. At 6 weeks (Time 3), sleep problems, edema, pain, fatigue, and shortness of breath were the most common. Number of symptoms decreased significantly between Times 1 and 3. All symptoms were more prevalent at Time 2 than at Time 1 and less prevalent at Time 3, with the exception of sleep problems, which were reported more frequently at Time 3 than at Time 1. The most persistent symptoms were edema, fatigue, sleep problems, pain, and shortness of breath. Significantly more middle-aged adults than older adults reported anxiety at Time 2. No other age-related differences were found. Implications for nursing practice and research are discussed. PMID- 8481680 TI - Wandering in Alzheimer's dementia patients. AB - The purpose of this research was to describe wandering behaviors of institutionalized patients with Alzheimer's disease in their natural environment. Such descriptive information is necessary before successful product and/or nursing intervention programs can be developed. Videotaped behavioral observations yielded detailed data descriptive of patients with middle and late dementia. These patients have the physical ability to perform various functions, activities, or actions; the individual's mental ability is less supportive of physical ability. The degree of task simplicity required to enable the patient to complete unsupervised tasks depends on the level of dementia. The need for interventions is greatest during unstructured periods of the day. PMID- 8481681 TI - Preterm infants in pain: nurses' and physicians' perceptions. AB - Within the past few years, the assumption that preterm infants experience little or no pain has been challenged in nursing and medical literature. It is not clear to what extent changes have taken place in the practice area. The purpose of this qualitative study was to explore the beliefs of NICU nurses and physicians about the existence and treatment of pain in preterm infants. Respondents to the open ended interviews were 5 neonatologists and 10 nurses at two regional referral neonatal intensive care units in North Carolina. Interviews took from 20 to 40 minutes and were analyzed using the Ethnograph program. All respondents agreed that preterm infants experience pain. Both groups identified behavioral and physiological cues to pain recognition. There were differences in initial approaches to treatment. However, both groups indicated that the nurse has the pivotal role in recognition and initiation of treatment to reduce or eliminate pain. PMID- 8481682 TI - Social skills training and cognitive restructuring for adolescents on hemodialysis. AB - The purpose of this study was to test a social skills and cognitive restructuring intervention designed for adolescents undergoing hemodialysis. A single-case experimental design with multiple baselines across subjects was used. Cognitive restructuring and assertive skills training were incorporated into eight weekly instructional modules. A convenience sample of 6 adolescents entered the program; 3 subjects completed the program. Data were analyzed using visual analysis. Although no striking changes could be seen between pre- and post-intervention phases for self-efficacy and self-report of assertive behaviors, there was a trend toward growth in overall social skills for 2 subjects. Another subject made some obvious increases in all areas of self-efficacy in comparison to other subjects. This study points out the merit of identifying depression as a factor in cognitive impairment and the exercise of personal efficacy. PMID- 8481683 TI - Complications of enteral nutrition in hospitalized patients with artificial airways. AB - This study investigated complications of enteral feeding in hospitalized patients with artificial airways. A prospective chart review, using a descriptive design, was used in this study of 51 inpatients in a large southeastern teaching hospital. A low (5.9%) incidence of pulmonary aspiration was found. Diarrhea was also found to be an infrequent complication (2%). The most common complication in this sample was interruption in continuous tube feedings: 24 patients (47%) experienced such interruptions, resulting in potential underfeeding. Further investigation of the adequacy of nutrition of hospitalized tube-fed patients with artificial airways is necessary to determine clinical significance. PMID- 8481684 TI - The human/animal bond as a correlate of family functioning. AB - This study investigated whether selected family characteristics are predictive of family functioning. The intent was to examine whether family cohesion and adaptability could be predicted from the characteristics of family education, income, marital status, and level of pet attachment. A survey research design was used to distribute questionnaires to families in therapy in six southeastern states. Findings indicated that 15% of the variance in family adaptability could be significantly (p < .05) accounted for by the combination of family education, income, marital status, and pet attachment. However, variance in family cohesion could not be significantly accounted for by this combination of variables. Family pet attachment was significantly (p < .05) correlated with both family adaptability and family cohesion. Clinical practice implications of these findings for nurses and other health care professionals are discussed, and recommendations for future studies are identified. PMID- 8481685 TI - Setting a research agenda to promote nursing research. AB - This study is a first step in the process of focusing research efforts in a developing nursing research program. A two-round Delphi technique, a method for formulating consensus, was employed to address the aim of organizationally reaching consensus regarding nursing research priorities. Questionnaires were mailed to "experts," defined as all registered nurses within the division (N = 634). Round 1 respondents identified 609 different research items, which were then sorted and categorized into a 100-item Round 2 questionnaire. Research directives and program planning will center around the priority areas. PMID- 8481686 TI - [Formation of a complex between glycogen phosphorylase and creatine kinase in rabbit skeletal muscles]. PMID- 8481687 TI - [Comparative-biochemical analysis of right-handed, left-handed, and ambidextrous rats]. PMID- 8481688 TI - [Participation of intestinal, hepatic and pulmonary basins in the formation of the lipid profile of blood and lymph in experimental atherosclerosis]. PMID- 8481689 TI - [A family of ankyrin-like orthopoxviridae proteins]. PMID- 8481690 TI - [The role of serotonin 1A and dopamine D2 receptors in buspirone effects on the electrical activity of white rat brain]. PMID- 8481691 TI - [Participation of met-enkephalin in the organization of the functional direction of the vagus effect on cardiac rhythm]. PMID- 8481692 TI - [Cytochrome P-448: study of oligomeric structure]. PMID- 8481693 TI - [Directed mutagenesis of bacterial formate dehydrogenase: the role of Cys-255 in the catalysis and stability of the enzyme]. PMID- 8481694 TI - [Paradoxical toxic effect and antagonism of O-(N-arylcarbamoylated) acylhydroxymoylchloride cholinesterase inhibitors with calcium]. PMID- 8481695 TI - [Anxiety as a possible cause for sex ratio disturbance in a generation ("the war years phenomenon")]. PMID- 8481696 TI - [Somnogenic effects of a delta-sleep peptide analog with an increased resistance to hydrolysis]. PMID- 8481697 TI - [Radiophosphene--an indicator of radiation stimulation of the central nervous system]. PMID- 8481698 TI - [New vectors for highly effective expression of hybrid proteins in E. coli]. PMID- 8481699 TI - [Migration of colonies of human epidermal keratinocytes in culture]. PMID- 8481700 TI - [Spontaneous instability of population waves formed by bacteria]. PMID- 8481701 TI - [EEG pharmacodynamics upon single administration of seduxen in healthy volunteers]. PMID- 8481702 TI - [Basic paths of morphological progress of the mammalian eye]. PMID- 8481703 TI - [Repeating DNA sequence present in pretelomeric segments of human chromosomes]. PMID- 8481704 TI - [Molecular-cytogenetic analysis of heterochromatin fragments induced by gene inactivation in the variegation position effect in Drosophila]. PMID- 8481705 TI - [Study of repeating DNA sequences in murine Ehrlich ascites cancer cells upon long-term mutagenic action]. PMID- 8481706 TI - [Mechanism of regulating the activity of glycogen phosphorylase b by adenosine-5' monophosphate]. PMID- 8481707 TI - [The role of nucleoside triphosphates in the motor reaction of living organisms]. PMID- 8481708 TI - National Advisory Committee on Immunization (NACI). Statement on pertussis immunization. PMID- 8481709 TI - The effect of proportion overlap and repeated testing on primed work fragment completion. AB - Subjects studied a list of words (e.g., cheetah) and received an implicit word fragment completion test (complete -h-t-h). On the test, the ratio of studied to nonstudied items (proportion overlap) was 0, 25, 50, 75, or 100%. Subjects were administered the identical test twice. Proportion overlap did not affect priming in word fragment completion, on either the first or second test. Also, the completion of studied and nonstudied fragments increased over repeated tests, but priming (the studied-nonstudied rate) remained unchanged. The proportion overlap of items between study and test does not affect performance on primed word fragment completion. PMID- 8481710 TI - Masking and visual field effects on a lateralized rod-and-frame test. AB - The rod-and-frame test (RFT) has been widely used in the study of sex differences in spatial abilities. However, laterality studies involving this test are very scarce. An experiment was conducted to investigate whether laterality effects would be affected by post-stimulus masking. Ninety-six subjects participated in the experiment. For half the subjects, stimuli were followed by a blank screen, while for the other half, stimuli were followed by a mask. An overall left visual field advantage (LVFA) was found in the task. An interaction of sex of subjects, masking conditions, and frame tilt was also found. Further analyses showed that the sex by angle of frame interaction was significant when a mask was presented after the stimuli, but not when no mask followed the stimuli. Data tended to confirm the hypothesis that the LVFA was only significant when a mask was presented after the stimuli. These findings demonstrate the usefulness of a masking procedure in visual field studies, whereas the right hemisphere advantage found on the RFT is consistent with previous findings with visuo-spatial tasks. PMID- 8481711 TI - Effects of distinctiveness, repetition and semantic priming on the recognition of face familiarity. AB - Three experiments are reported which provide evidence for the independence of effects of repetition from those of distinctiveness and semantic priming in the recognition of familiar faces. In Experiment 1, repetition priming is shown to be additive with face distinctiveness in a face familiarity decision task, where subjects make speeded familiarity decisions to a sequence of famous and unfamiliar faces. Experiment 2 examines the combined effects of distinctiveness and semantic priming. The results suggest that the effect of distinctiveness is additive with that of semantic priming. Experiment 3 uses a more powerful design in which effects of distinctiveness and semantic priming were assessed while all items were repeated three times during the course of the experiment. Effects of repetition and distinctiveness were again additive, as were effects of repetition and semantic priming. Distinctiveness and semantic priming were additive at 1,000 ms SOA, though appeared to interact at 250 ms SOA. The results give further evidence for the separation of the mechanisms of semantic from repetition priming, and furthermore suggest that distinctiveness operates at a different locus from those of either of the priming mechanisms. PMID- 8481712 TI - Eye movement control during visual object processing: effects of initial fixation position and semantic constraint. AB - Eye movement patterns were recorded while subjects viewed arrays of line drawings of objects. The initial landing position of the eyes on an object was found to be normally distributed around the center of the object, with the modal landing position at the center. Landing variability was greater in the direction of the eye movement vector than in the direction perpendicular to the movement, and there was more of a tendency to undershoot the center of the object than to overshoot it. Landing position was found to influence other aspects of eye movement behaviour. The duration of the first fixation on an object decreased and the probability of refixating an object increased as the deviation of the initial landing position from the center of the object increased. The effect of a cognitive factor, semantic constraint, was also examined. Landing position and semantic constraint were found to interact such that semantic constraint had a greater effect the further the eyes landed from the center of the object. The results are discussed in terms of their implications for the use of eye movement behaviour as an indicator of perceptual and cognitive processing. PMID- 8481713 TI - [Attention behavior of infants and modulation of maternal language]. AB - Language spoken to infants has several peculiarities that are also found in other cultures. In this study we have examined the specific relationships between some infant's behaviours and the prosodic modulations of maternal speech in a face to face interaction. 14 mothers with their four month-old infant were observed in a laboratory setting in order to obtain a corpus of 2100 maternal words. There is a variation of maternal speech prosody that depends upon the attentional behaviours of the infant. When the infant is interacting (the gaze is directed towards the mother with a neutral or positive expression, joint gaze), the mother has a tendency to produce longer utterances with a more variable fundamental frequency than that observed when the infant is not interacting (looking elsewhere or alternating). There is also a larger occurrence of complex and bell-shaped curves during the infant's positive and joint gazes. The infant appears to be an active partner in mother-infant verbal exchange. PMID- 8481714 TI - History of laparoscopy: urology's perspective. PMID- 8481715 TI - Perirenal hematomas caused by SWL with EDAP LT-01 lithotripter. AB - A total of 419 calculi in the upper urinary tract of 402 patients were treated by SWL with the EDAP LT-01 lithotripter from July 1988 to September 1989. Subcapsular hematomas resulted in 17 kidneys of 16 patients, an incidence of 4.1%. On CT scan, fractures with subcapsular hematomas were observed in nine kidneys, and a retroperitoneal hematoma was observed in one patient. There was no significant difference in stone location and size, grade of hydronephrosis, number of shock waves, applied energy, or post-treatment fever between the groups with and without hematomas. However, the hematoma group revealed significantly (P < 0.01) higher incidences of pretreatment hypertension (> 160/95 mm Hg) and use of antiplatelet agents. It is difficult to detect some disorders of blood coagulation in ordinary laboratory studies in patients receiving low dosages of antiplatelet agents; and many drugs including analgesic and anti-inflammatory agents, calcium antagonists, coronary vasodilators, antiplatelet agents, beta blockers, and lipid-regulating agents have antiplatelet actions. Therefore, particular care should be taken in SWL when a patient is using those drugs. PMID- 8481716 TI - Absence of long-term gonadotoxicity in primates receiving extracorporeal shock wave application. AB - Extracorporeal shock wave lithotripsy (SWL) is becoming popular in the management of lower ureteral calculi; however, the quantity of data on its potential gonadotoxic effects are limited. Eight nonhuman primates had baseline measurements of testicular volume, semen analysis, serum testosterone and FSH assays, and DNA flow cytometric analysis of testicular aspirates. The anesthetized primates were lowered into a Dornier XL-1 lithotripter and at a 20 kV power setting had various numbers of shocks (0, 500, 1500) directed at each testis. Sequential studies were done at 6-week intervals for 9 months. The control group showed no significant change in any measure. Semen analysis, testosterone, and FSH results were variable and without statistically significant differences. There were changes in the DNA histograms, with the tetraploid (4N) group of cells being the most sensitive. All changes caused by SWL application returned to baseline by 9 months. Data from this primate study document no apparent long-term male gonadotoxicity from SWL, but the authors suggest measures to protect the testis during clinical use. PMID- 8481717 TI - Retroperitoneal laparoscopic nephrectomy: laboratory and clinical experience. AB - Laparoscopic nephrectomy using an entirely retroperitoneal approach was performed in six anesthetized female pigs. In each animal, the kidney was localized using fluoroscopy, following which the retroperitoneum was insufflated with CO2. Subsequently, a retroperitoneal laparoscopic nephrectomy was performed in a 48 year-old man with a chronically obstructed, nonfunctioning kidney. Although the retroperitoneal approach provides excellent exposure for the dissection of the renal hilum, anatomic factors in the human limit port placement and organ entrapment and increase the risk for development of a pneumothorax. PMID- 8481718 TI - Laparoscopic nephropexy for symptomatic nephroptosis: initial case report. AB - Laparoscopic nephropexy was performed in a 25-year-old woman with intractable pain and a palpable pelvic mass associated with right nephroptosis for more than 1 year. Evaluation by a supine and an erect intravenous urogram (IVU) revealed right renal descent of three vertebral bodies with mild hydronephrosis. Laparoscopic transperitoneal nephropexy was performed in a 2 and a half hour procedure. The patient stayed in the hospital 2 days postoperatively and returned to full activities 3 weeks later. At 2 months postoperatively, she is asymptomatic. An upright IVU2 months postoperatively revealed renal descent of only one vertebral body and no hydronephrosis. This is the first report to our knowledge of a successful laparoscopic nephropexy. PMID- 8481719 TI - Omental evisceration through small laparoscopy port sites. AB - Two children developed omental evisceration through small periumbilical port sites after peritoneal endoscopy for nonpalpable testes. Factors that predispose to this complication include decompression of the pneumoperitoneum by suction. These factors and steps to avoid it such as closure of all endoscopic fascial defects under direct vision are described. PMID- 8481720 TI - New tip design and shock wave pattern of electrohydraulic probes for endoureteral lithotripsy. AB - A new tip design of a 3.3F electrohydraulic probe for endoureteral lithotripsy was evaluated in comparison to a regular probe. The peak pressure, as well as the slope of the shock front, depend solely on the voltage. Increasing the capacity leads merely to broader pulses. A laser-like short high-pressure pulse has a greater impact on stone disintegration than a corresponding broader low-pressure pulse of the same energy. Using the regular probe, only positive pressures were obtained. Pressure distribution around the regular tip was approximately spherical, whereas the modified probe tip "beamed" the shock wave to a great extent. In addition, a negative-pressure half-cycle was added to the initial positive peak pressure, which resulted in a higher maximal pressure amplitude. The directed shock wave had a greater depth of penetration into a model stone. Thus, the ability of the new probe to destroy harder stones especially should be greater. The trauma to the ureter was reduced when touching the wall tangentially. No difference in the effect of the two probes was seen when placing the probe directly on the mucosa. PMID- 8481721 TI - Endopyelotomy and endoureterotomy with the acucise ureteral cutting balloon device: preliminary experience. AB - Endoureterotomy and endopyelotomy usually involve an endoscopic antegrade approach. In an effort to simplify this technique, we designed an 8-mm balloon catheter with a 100-microns electrocautery cutting wire (Acucise) for retrograde incision of the ureter under fluoroscopic control. Twenty-eight patients with ureteral or ureteropelvic junction obstruction of 3.5 cm or less underwent Acucise endoureterotomy or endopyelotomy. The average operating time was 100 minutes, and the average hospital stay was 2.6 days. Follow-up was obtained with a subjective symptom score, intravenous urography, diuretic renal scan, a Whitaker test, or various combinations thereof. All patients had a minimum of 3 months of follow-up (mean 3.8 months; range 3-9 months). Overall, of the 21 patients who had symptoms of upper tract urinary obstruction, 14 (67%) had complete resolution, and another 4 (19%) had partial resolution, of their symptoms. Postoperative studies demonstrated normal upper tracts in 71% and improvement in another 14% of the patients. In our experience, the Acucise ureteral cutting balloon device provides an effective and efficient means for performing a retrograde endoureterotomy or endopyelotomy. PMID- 8481722 TI - Endoscopic use of Nd:YAG laser to remove Marlex strut from Kock continent urinary reservoir. AB - A Marlex strut, which was designed to prevent efferent valve prolapse and peristomal herniation in the Kock continent urinary reservoir, eroded through the pouch wall, resulting in persistent bacteriuria and the inability to catheterize the pouch. The eroding strut was removed endoscopically with the Nd:YAG laser. Continence has been preserved and ease of catheterization restored. PMID- 8481723 TI - New temporary coil stent (Urocoil) for treatment of recurrent urethral strictures. AB - The Urocoil is a temporarily inserted self-expanding and self-retaining coil stent made of medical-grade stainless steel that is inserted under fluoroscopy after topical anesthesia of the urethra. This stent was used for 16 patients with a variety of recurring urethral strictures who had been managed in the past by repeated dilatations and urethrotomies. The stent was left in place for 6 months. Unlike permanently implanted mesh stents, no tissue growth into the lumen occurred with this stent, making its removal a simple procedure. With a follow-up of 3 to 9 months after removal, no recurrence of the strictures was observed. This temporary stent seems to be effective in the treatment of recurring urethral strictures. Satisfactory and promising results were obtained without leaving a foreign body permanently in the urethra. PMID- 8481724 TI - Extracorporeal shock wave lithotripsy for calcified ureteral stent. AB - Calcification of a ureteral stent has been an unusual complication of long-term stent use for bypassing ureteral obstruction or after surgical repair. Open or percutaneous procedures have usually been required to remove the calcification before the stent can be extracted. We report six cases of calcified ureteral stents successfully managed by extracorporeal shock wave lithotripsy (SWL) followed by cystoscopic extraction, thus avoiding open or percutaneous procedures. PMID- 8481725 TI - Efficacy of endoscopic hydrocele ablation. AB - We describe a new endoscopic technique that was used for the treatment of symptomatic scrotal hydroceles in 10 men. Through a small skin incision, the parietal surface of the tunica vaginalis was ablated endoscopically using either electrocautery or the KTP:YAG laser. This approach permitted visual inspection of the scrotal contents with minimal manipulation and was performed using monitored local anesthesia with bilateral spermatic cord blocks. With a mean follow-up interval of 6.1 months, no hydrocele recurrences, wound infections, or hematomas have been detected. The mean operative time was comparable (53 minutes) to that in a historical control group consisting of 15 men who had undergone open hydrocelectomy at our institution (46 minutes). Postoperative scrotal discomfort was minimal, with 6 of the 10 patients requiring no analgesics. Patients were able to resume their preoperative lifestyles an average of 2 days after surgery. In contrast, 11 of the 15 men in the control group was still complaining of scrotal pain, requiring oral analgesics, at their 2-week follow-up visit. Thus, endoscopic hydrocele ablation appears to be an effective and well-tolerated alternative to treat hydroceles with minimal postoperative discomfort. PMID- 8481726 TI - Relationship of fluid intake to voluntary micturition and urinary incontinence in geriatric patients. AB - The aim of this study was to investigate, in a group of geriatric inpatients with established incontinence, the relationships among urine loss, voided volumes, frequency of voiding, and fluid intake. The investigated included 128 patients: 76 women and 52 men, with a median age of 79 years. One-half had significant cognitive impairment. Patients underwent 24-hr monitoring of fluid intake, urine loss, and voiding, as well as conventional videourodynamic testing. Diurnal and nocturnal voiding frequencies were significantly but relatively weakly related to fluid intake. Diurnal and nocturnal voided volumes were more closely related, however, to the fluid intake. There was a strong and easily interpretable relationship among nocturnal voided volume, nocturia, cystometric bladder capacity, and evening fluid intake. Sixty of 128 patients had urodynamically proven urge incontinence, and this group was studied separately. They were more cognitively impaired and had significantly greater urine loss and smaller fluid intake than was true of the other incontinent patients. Urine loss was significantly related to fluid intake in this group. Nocturnal urine loss increased by an average of 28 ml/dl of evening fluid intake and decreased by 17 ml/dl voided at night. These results suggest that nocturnal toileting and evening fluid restriction may reduce nocturnal urine loss by a small but useful amount in carefully selected older patients with severe urge incontinence. PMID- 8481727 TI - Time-series analysis of urethral electrical conductance measurements in the assessment of unstable urethral pressure: results in normal patients and in those with genuine stress incontinence. AB - It is well established that urethral pressure variations occur in patients with or without urinary incontinence, but to what extent they contribute to a patient's symptoms remains unclear. Previous work has suggested that in stress incontinent patients, a rise in bladder neck electrical conductance (BNEC) occurs simultaneously with a fall in urethral pressure, and that this represents bladder neck opening. Six patients with genuine stress incontinence (gsi), and six normal controls underwent simultaneous urethral pressure and BNEC measurements, the results being subjected to time-series analysis, to determine whether the previous finding could be confirmed statistically, and to establish whether a similar association was present in normal women. All six patients with gsi and five of the normal patients had unstable urethral pressure. Estimated cross correlation of differenced data for the two parameters showed a significant negative correlation at zero time lag in three patients with gsi and two of the control group. There was no significant correlation between the two parameters in the other seven patients. We conclude that the previous finding of a correlation between urethral pressure variation and BNEC, suggesting bladder neck opening occurs as urethral pressure falls in patients with gsi is confirmed, but appeared to be present in only 50% of patients; the finding is just as likely in normal patients, and therefore whilst it may be of relevance to the severity of symptoms, could not be held to have any aetiological significance. PMID- 8481728 TI - Uroflowmetry in the puerperium. AB - One hundred women underwent uroflowmetry once per day for the first 3 days after delivery, and the results compared to those of 53 nonpregnant controls in an effort to determine 1) whether urinary flow in the puerperium is different to that found without pregnancy, 2) whether uroflow parameters change as the puerperium progresses, and 3) which characteristics of a patient or her labour bear most influence upon the results of uroflowmetry. Urinary flow in the puerperium was seen to be different from that of the nonpregnant female in that mean flow rates were lower. In addition to this, voided volume, total flow time, and time to peak flow were all significantly increased on day 1, but were comparable on days 2 and 3. Other than for falling voided volumes, uroflow parameters did not alter significantly as the puerperium progressed. Correlation of the variables age, parity, baby weight, length of first and second stage, use of epidural and perineal suturing with the parameters of urinary flow failed to show any significant relationship. PMID- 8481729 TI - Urothelial permeability of the isolated whole bladder. AB - The urothelium of the bladder presents an effective barrier to the penetration of solutes from the urine into the bladder wall. Previously, we have demonstrated that the dye indigocarmine can be utilized intravesically to study urothelial permeability. In general, intravesical indigocarmine (administered in vivo) will not penetrate the bladder wall unless the urothelium is damaged by overdistension, acetone administration, or mechanical damage. Unfortunately, using in vivo methodologies, one is limited in the study of the effect of specific conditions and permeations on bladder permeability. In the current study an isolated in vitro whole bladder model was developed to quantitatively study the permeability of the bladder urothelium. In these studies, the penetration of indigocarmine into and through the bladder wall was quantitated under various conditions. The in vitro bladder was filled by infusing 1% indigocarmine in saline in a step-wise manner at the rate of 10 ml in 10 minutes followed by a stabilization period of 10 minutes. Samples were taken from the bath at 20 minutes intervals for spectrophotometrical analysis of the dye. At the end of experiment the bladder was washed in saline for 10 minutes, and stored and extracted in formalin. In general, no indigocarmine penetrated the urothelium until the in vitro capacity was reached and exceeded. At intravesical volumes greater than capacity, the dye concentration in the bath increased very rapidly, even though the integrity of the bladder wall remained intact. In bladders treated with a gentle 50% acetone wash for 1 minute the dye started to penetrate into the bath at intravesical volumes of 25% of capacity and increased rapidly thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481730 TI - A model of the mechanics of smooth muscle reservoirs applied to the intestinal bladder. AB - A model of the mechanics of smooth muscle reservoirs was derived from the stress strain relation in smooth muscle strips. The model was applied to the intestinal bladder reservoir but may also be applied to natural reservoirs such as the bladder. The relation between reservoir volume and pressure was calculated at different values of smooth muscle tone and was found to accord with clinical results. The muscle tone of the bowel when measuring off the bowel to construct the reservoir was found to have a profound influence on its ultimate volume. Stiffening of a part of the reservoir wall as a result of edema or fibrosis will cause a substantial decrease in functional capacity, both directly as a result of a reduced expansion of the diseased part and indirectly by enhancing the stretching of the adjacent normal wall. The pressure rise produced by a slow peristaltic contraction was calculated to depend both upon the strength of contraction and on the degree of reservoir filling: Almost no pressure rise will occur in the near empty reservoir, while the highest pressure rise was calculated to occur at a volume of about 300 ml. If only a part of the reservoir contracts, more filling is needed before the pressure increases and the maximum pressure will be reached at a substantially higher volume. Localized contractions will stretch the resting reservoir wall and so activate stretch receptors, which may cause a desire to void, resulting in reduced functional capacity. PMID- 8481731 TI - Sacral spinal cord and root potentials evoked by the stimulation of the dorsal nerve of penis and cord conduction delay for the bulbocavernosus reflex. AB - Segmental spinal cord and root potentials in response to stimulations of the dorsal nerve of penis, tibial nerve, and the sural nerve were epidurally recorded in normal subjects. EMG responses from the bulbocavernosus (BC) and the various leg muscles were also recorded in response to bipolar stimulations by the same epidural needle electrodes of the sacral cord and lumbosacral roots. The afferent conduction velocity from the penis to Th12-L1 intervertebral level was about 40 m/sec on the average, which is significantly slower than those obtained by the stimulation of the mixed and cutaneous nerves at the lower limb. The latency of the motor responses of the BC muscle from Th12-L1 spine levels were found comparatively longer than those of thigh muscles on maximal epidural stimulation in spite of the shorter distances to the BC muscle. The central conduction delay within the sacral cord of the bulbocavernosus reflex was calculated and found to be about 8.2 msec, while the central conduction time was about 1.1 msec for the Soleus-H-Reflex. These findings may suggest that there may be about 5-6 synapsis necessary for the first component of the bulbocavernosus reflex, though some faster oligosynaptic cord linkage may also exist. PMID- 8481732 TI - Regulation of the bladder neck closure by lumbar splanchnic nerves at ejaculation in the dog. AB - To clarify the role of canine thoracolumbar splanchnic nerves for bladder neck closure during ejaculation, these nerves of adult male mongrel dogs were exposed under anesthesia using ketamine hydrochloride and pentobarbital, and electrical stimulation and anatomical dissection studies were performed. Bladder neck closure by the stimulation of each sympathetic nerve was monitored with a 10 Fr silicon catheter equipped with pressure-sensitive rubber balloon placed at the bladder neck. The dissection study revealed that canine thoracolumbar splanchnic nerves consisted of two nerve groups: one branching from the sympathetic trunks at thoracic and L1 ganglia, reaching caudal mesenteric plexus (CMP) through the anterior wall of the aorta, the other branching from the sympathetic trunks at level L2-L5 ganglia, reaching CMP through the posterior side of the bilateral spermatic arteries. The former were designated intermesenteric splanchnic nerves, the latter lumbar splanchnic nerves. No bladder neck closure was observed by electrical stimulation of the distal end of severed intermesenteric splanchnic nerves or of the sympathetic trunks at the lumbopelvic level among 10 dogs examined. At least one lumbar splanchnic nerve generated the closure in all 10 dogs and generally, a few lumbar splanchnic nerves, generated the closure. The results indicate that bladder neck closure during ejaculation is generated by lumbar splanchnic nerves regardless of their branching levels from lumbar sympathetic ganglia, but not by either intermesenteric splanchnic nerves or pelvic sympathetic trunks. PMID- 8481733 TI - Effect of cromakalim on micturition function in rats. AB - Although many studies investigating the effect of cromakalim on bladder contractility exist, thus far, there are no published studies investigating its effect on micturition function in conscious rats. We measured the effect of cromakalim i.v. on urine output, frequency, volume of each micturition, and blood pressure in saline-diuresed and non-diuresed rats. In saline-diuresed rats cromakalim produced significant decreases in urine output (0.1 mg/kg, 32%; 0.3 mg/kg, 46%; 1.0 mg/kg, 68%) and average frequency (0.1 mg/kg, 36%; 0.3 mg/kg, 51%; 1.0 mg/kg, 70%) in the first 3 hours. At 3-6 hours after administration of cromakalim there were rebound increases in both urine output (0.1 mg/kg, 290%; 0.3 mg/kg, 373%; 1.0 mg/kg, 538%), and frequency (0.1 mg/kg, 147%; 0.3 mg/kg, 181%; 1.0 mg/kg, 314%) and by 6-12 hours the effects of cromakalim on micturition function were gone. Mean arterial pressure dropped to 50% of control immediately after cromakalim administration in saline-diuresed rats and began to return to control levels after 3 hours. Cromakalim produced similar results in non-diuresed rats. The decrease in urine output 0-3 hours after cromakalim administration may have been a consequence of cromakalim's profound decrease in blood pressure that occurred during that time. PMID- 8481734 TI - Clinicopathological studies of the dementias from an epidemiological viewpoint. AB - Studies which examine patients with and without dementia during life and then examine brain tissue after death are extremely difficult to conduct. There are now several such studies published, representing a major contribution to the understanding of the pathologies of the dementias. These studies were not designed to represent population samples and, from an epidemiological viewpoint, they are flawed because none are population-based and none represent the full range of function observed during life. It is therefore important to examine the available studies for their contributions and biases. PMID- 8481735 TI - The medical complications of anorexia nervosa. AB - The physical complications of anorexia nervosa are common and can be life threatening, but psychiatrists and the increasing number of non-medical therapists involved in treatment programmes often overlook these complications. Cardiovascular complications are the most common, and the most likely to result in fatalities, particularly in those patients who vomit, purge or abuse diuretics, because of the electrolyte abnormalities induced. Osteoporosis is an early and perhaps irreversible consequence of severe weight loss. Further, there are dangers in rapid intravenous hyperalimentation. PMID- 8481736 TI - Attitudes of British psychiatrists to the diagnosis of somatisation disorder. A questionnaire survey. AB - A postal questionnaire was sent to 195 senior British psychiatrists who were asked about their attitudes towards the DSM-III-R diagnosis of somatisation disorder (SD) and the ICD-10 diagnosis of multiple somatisation disorder. Of the 148 respondents, 98 (66%) had experience of liaison psychiatry, and these psychiatrists used the diagnosis significantly more often than those without liaison sessions. More than half the respondents perceived SD as both a personality disorder and a mental state disorder, although 27% thought that patients with SD had an undiagnosed physical disease. The marked discrepancy between British and North American psychiatrists in diagnostic practices was perceived to be a consequence of both the difference in health care systems and the interest shown in the disorder by North American psychiatrists, rather than a reflection of genuine differences in prevalence. PMID- 8481737 TI - Techniques for interviewing the somatising patient. AB - Liaison psychiatrists need to interview somatising patients in a way which allows a full assessment of the problem. This can best be achieved if the psychiatrist has already discussed with the referring physician the reason for referral and what the patient has been told about it. The medical notes should always be reviewed in detail and independent data obtained from a relative or other informant. During the interview itself the psychiatrist must be prepared to use techniques which deepen rapport with the patient, who may be initially wary or hostile. The psychiatrist should attempt to establish early a treatment alliance. Special aspects of the mental state need to be noted, including the patient's attitude to his/her symptoms and the strength with which somatic beliefs are held. Different approaches may be used according to the nature of the problem and the therapeutic style of the doctor. An awareness of these interview techniques would greatly reduce the chances of fruitless interviews with a hostile patient who believes the symptoms are being dismissed as being 'all in the mind'. PMID- 8481738 TI - The management of chronic somatisation. AB - 'Somatisation' is a process in which there is inappropriate focus on physical symptoms and psychosocial problems are denied. In some patients this process becomes chronic (in excess of six months). Special skills and strategies are required by non-psychiatrists to manage these patients, for whom the acceptance of psychiatric treatment should be facilitated. When taking the history, doctors should be aware of psychosocial cues; thereafter they should be consistent and unambiguous in their management. An agenda should be set early on, with limits on investigations. Failure to manage this group of patients is costly, and further intervention studies are required not only to reduce health service and other costs, but also to relieve the non-monetary burden of physical and psychosocial disability on patients and their relatives. PMID- 8481739 TI - The premenstrual syndrome: a twin study. AB - Data are presented from 157 monozygotic and 143 dizygotic female twin pairs of reproductive age who completed a self-report questionnaire on the premenstrual syndrome (PMS). For global PMS scores, the correlation coefficient for the monozygotic twins (0.55) was double that of the dizygotic ones (0.28). The results are consistent with the hypothesis that aggregation for global PMS scores is determined by genetic factors acting additively over a number of loci. Two alternative explanations are suggested: that monozygotic twins share greater environmental similarities than dizygotic ones; or that PMS scores may be a reflection of some other underlying characteristic (such as neuroticism), which is itself genetically determined. PMID- 8481740 TI - Delusions in children and teenagers admitted to Bethlem Royal Hospital in the 19th century. AB - The case notes of 1069 children and teenagers admitted to Bethlem Royal Hospital ('Bedlam') in the 19th century were analysed with particular reference to the frequency and types of delusions. Delusions were present in 700 (65%), among whom there were significantly more boys than girls. There was a statistically significant rise in the frequency of delusions from 1830 to the end of the century. Sixty-six per cent of the patients were discharged cured and, taken overall, the presence of delusions did not affect the prognosis: specifically, delusions did not worsen the prognosis in those diagnosed as suffering from mania or melancholia. Nevertheless, the prognosis was worse in boys with single paranoid delusions, or paranoid delusions in combination with auditory hallucinations of people, and worse for girls with delusions of exaltation in combination with other types of delusions. PMID- 8481741 TI - The postconcussional syndrome: social antecedents and psychological sequelae. AB - The study consisted of a prospective investigation of 45 consecutively admitted patients who had sustained a mild head injury. In all cases the duration of post traumatic amnesia was less than 24 hours. Head injury patients had an average of three adverse life events in the year preceding injury compared with 1.5 for controls. Using the PSE, 39% of the group were diagnosed psychiatric cases at six weeks after the injury. For cases the mean level of chronic social difficulties (3.3) was four times that for non-cases (0.8). Six months after injury, 28% of the head injury group had three or more symptoms. These chronic cases were on average ten years older than those whose symptoms had remitted. Chronic cases had, on average, three social difficulties, twice as many as found among those whose symptoms had remitted. The emergence and persistence of the postconcussional syndrome are associated with social adversity before the accident. While young men are most at risk of minor head injury, older women are most at risk of chronic sequelae. PMID- 8481742 TI - How important is the assessment of social skills in current long-stay in patients? An evaluation of clinical response to needs for assessment, treatment, and care in a long-stay psychiatric in-patient population. AB - Service response to problems in 20 clinical and social competence areas was assessed in 156 long-stay in-patients, using the Needs for Care Assessment (NFC). Although there were few unmet needs for treatment, over 200 instances of unmet needs for the assessment of social skills were found, and reasons for this are discussed, as is the importance of social-skills assessment in this group. In around a third of the sample most of the social-skill areas in the NFC were not applicable. PMID- 8481743 TI - The adult adjustment of offspring of parents with drinking problems. AB - One hundred and sixty-four 16-35-year-old offspring of parents with drinking problems, recruited from a variety of clinical and community sources, were compared with 80 respondents of similar ages from similar sources who did not have parents with drinking problems. Each was interviewed using a semistructured interview. Adult adjustment was similar in the two groups, but the offspring of parents with drinking problems did report considerably more disharmony in their families of origin, and many more childhood difficulties. Factor analysis of the adult adjustment data for the samples combined showed four factors which accounted for 41% of the variance; these factors differed little in their effect in the two groups. The groups' reports of the drinking problems of their siblings, however, suggests that this sample might be unrepresentative of the true risk to the children of parents with drinking problems for the development of alcohol-related (although not other) difficulties in adulthood: 16% of this group reported a sibling with a drink problem and a further 9% were unsure, but only one member of the comparison group reported a sibling with a drink problem, and one was unsure. Path analysis showed that both parental problem drinking and family disharmony are related in complex ways to adjustment difficulties in adulthood. 'Demoralisation', the largest of the four factors, was particularly related to disharmony in the family of origin: in the absence of disharmony, offspring versus comparison status was negatively correlated to demoralisation in adulthood, suggesting that having a parent with a drinking problem might sometimes be a strengthening experience. PMID- 8481744 TI - Head circumference in 'preschizophrenic' and control neonates. AB - Head circumference, body weight, body length, and shoulder circumference at birth were studied in 70 RDC schizophrenic patients and 70 demographically matched controls from the same delivery series, using information recorded in the medical records at the time of birth. With preterm babies removed from both samples, only head circumference among preschizophrenic infants was significantly smaller than that of controls. Preschizophrenic infants also had a disproportionately smaller head circumference in relation to body length than did controls. Among the former, a small head circumference was systematically related to an absence of family history of psychosis, but was not related to season of birth or recorded pregnancy complications. The findings were strongest for females. The results suggest there is an unidentified non-genetic factor in schizophrenia that disturbs prenatal cerebral development. PMID- 8481745 TI - A trial of two cognitive-behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients: I. Outcome. AB - Despite neuroleptic medication, many schizophrenic patients continue to experience residual positive psychotic symptoms. These residual symptoms cause distress and disability. We report a controlled trial of two cognitive behavioural treatments to alleviate residual hallucinations and delusions. Forty nine patients were recruited into the trial, of whom 27 entered the trial and completed post-treatment assessment, and 23 were reassessed at six-month follow up. Patients were randomly allocated to either coping strategy enhancement (CSE) or problem solving (PS). Half the patients were allocated to a high-expectancy positive demand condition and half to a counter-demand condition to evaluate expectation of improvement. Patients receiving either cognitive-behavioural treatment showed significant reductions in psychotic symptoms compared with those in the waiting period, who showed no improvement. There was some evidence, although equivocal, that patients receiving CSE improved more than those receiving PS. There was no evidence that improvements generalised to negative symptoms or social functioning, nor was there evidence that expectancy of treatment benefit contributed to the treatment effect. PMID- 8481746 TI - Institutionalisation and the long-term course of schizophrenia. PMID- 8481747 TI - A proposal to classify happiness as a psychiatric disorder. PMID- 8481748 TI - Caffeine: use and effects in long-stay psychiatric patients. AB - In a double-blind crossover study of 26 long-stay schizophrenic patients, no correlation was found between caffeine consumption and levels of anxiety and depression. No significant changes in patients' behaviour or levels of anxiety and depression occurred when the wards changed to decaffeinated products. Serum caffeine levels confirmed compliance. No evidence was found to support a removal of caffeinated products from this group of patients. PMID- 8481749 TI - Munchausen's syndrome and organic brain disorder. AB - A case of Munchausen's syndrome was probably caused by brain damage sustained during a necessary cholecystectomy. Doctors should not be discouraged from seeking treatable disorder because of such patients' behaviour. PMID- 8481750 TI - Behavioural sensitisation and steroid-induced psychosis. AB - As yet, there is no satisfactory model with which to understand steroid-induced mental disorder. It is suggested that a case of prednisone-induced psychosis in an adolescent female with Crohn's disease can be best understood in terms of behavioural sensitisation to steroid therapy. PMID- 8481751 TI - Cross-dressing in men with learning disabilities. AB - Four men with learning disabilities were considered to show transvestic fetishism, and a fifth to show transvestism. However, developmental retardation and personality problems may modify the concepts behind such categorisation. PMID- 8481752 TI - Erotic target location errors in male gender dysphorics, paedophiles, and fetishists. PMID- 8481753 TI - Puerperal affective psychosis: is there a case for lithium prophylaxis? PMID- 8481754 TI - Puerperal affective psychosis: is there a case for lithium prophylaxis? PMID- 8481755 TI - Assessment of insight in Singapore. PMID- 8481756 TI - In defence of clozapine. PMID- 8481757 TI - Clozapine, cognition, and schizophrenia. PMID- 8481758 TI - Mentally ill sex offenders. PMID- 8481759 TI - Mabi bark tea. PMID- 8481760 TI - 'Hidden' spending on community services. PMID- 8481761 TI - HIV infection, serotonin, and sexual dysfunction. PMID- 8481762 TI - Hysteria in childhood. PMID- 8481763 TI - Folate and depression. PMID- 8481764 TI - Outdated ECT machines. PMID- 8481765 TI - Parental age in schizophrenia in a case-controlled study. PMID- 8481766 TI - Women's labour force participation and socioeconomic development: influences of local context and individual characteristics in Brazil. AB - We address several key hypotheses about the effects of socioeconomic development on women's labour force participation during the transition from agriculture to industrialism. To this end, we explore differences in women's labour force participation in Brazil by education, marital status, age, and urban or rural residence. We also show how socioeconomic development affects the overall level of women's participation and the differentials by education, etc. Our data are drawn from a large 1973 PNAD (Pequisa Nacional por Amostra de Domicilos) survey conducted by the Brazilian census bureau. Socioeconomic development in different parts of Brazil ranges from pre-industrial agriculture to heavy industry. Using logistic regression, we show that the general level of women's labour force participation does not change with the level of development. Highly educated women are much more likely than the less educated to be in the labour force (net of other influences); this difference is substantially greater than in post industrial societies. Somewhat surprisingly, the influence of education is the same across the range of development levels in Brazil. Single women are more likely to be in the labour force than married women, and the difference grows during development. Age has a curvilinear relationship to labour force participation, and the old are much less likely to participate in more developed places. Rural women are slightly more likely to be in the labour force at all levels of development. PMID- 8481767 TI - Intraocular co-grafts of fetal dorsal raphe nucleus and suprachiasmatic nucleus. AB - Serotonergic neurons in the fetal dorsal raphe nucleus were grafted together with fetal anterior hypothalamic tissue including the suprachiasmatic nucleus (SCN) to the anterior eye chamber of adult rats. After 6 weeks transplantation, the double grafts were immunocytochemically examined using antisera against serotonin, arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP). The raphe grafts contained a large number of serotonin-immunoreactive neurons and fibers, but only a few AVP-immunoreactive fibers and VIP-immunoreactive neurons and fibers. On the other hand, numerous AVP- and VIP-immunoreactive neurons and fibers were found in the SCN of the anterior hypothalamic graft. Outgrowing serotonin-immunoreactive fibers from the raphe tissue were densely distributed in the anterior hypothalamic graft. In the SCN, however, only a few fibers were detected. The results demonstrate that the isolated anterior hypothalamic grafts can be innervated by the serotonergic neurons from the raphe grafts, but the innervation pattern of these fibers was quite different from the normal rat. The present results indicate that the isolated SCN has an inhibitory influence on the growth of serotonergic fibers. PMID- 8481768 TI - Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro. AB - There is now considerable evidence that nitric oxide (NO) is an important neuroregulatory agent, but there has been very little investigation of the possible role of NO in neuroendocrine mechanisms. We have previously shown that acute rat hypothalamic explants can be used to study the regulation of hypothalamic neuropeptide release, and we have now utilised this experimental approach to investigate the putative involvement of NO in the control of the principal corticotropin-releasing hormone, CRH. We studied the direct effects of the NO precursor L-arginine (L-ARG), as well as the NO donors molsidomine and sodium nitroprusside, on both the basal and stimulated release of CRH; the stimuli used were non-specific depolarisation with potassium chloride (KCl) and the specific cytokine, interleukin-1 beta (IL-1 beta; 100 U/ml). L-ARG was tested in each experimental condition with and without contemporaneous addition of its competitive antagonist NG-monomethyl-L-arginine (L-NMMA). IL-1 beta-induced CRH release was also investigated in the presence of D-arginine (D-ARG), which is not active as a precursor to NO, and ferrous hemoglobin (Hb), a substance which is a potent inactivator of NO. None of the NO precursors (L-ARG, molsidomine, sodium nitroprusside) or antagonists (L-NMMA or Hb) was able to affect basal CRH release. However, L-ARG 10 and 100 microM were found to significantly inhibit the release of CRH induced by 40 mM KCl; CRH fell to 45% of its stimulated level at the higher dose of L-ARG. This effect was attenuated in the presence of L-NMMA at a ten-fold higher dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481769 TI - Calcium-binding proteins in the chick Edinger Westphal nucleus. AB - It has been suggested that the calcium-binding proteins, parvalbumin and calbindin-D28K, are involved in the control of intracellular calcium levels but their exact functions are unknown. Immunoreactivity for parvalbumin has been associated with rapidly firing cells, while calbindin has been implicated in protecting neurons from excitotoxicity. Since the chick Edinger Westphal nucleus contains two populations of neurons with different firing patterns, parvalbumin and calbindin immunoreactivities were examined in the Edinger Westphal nuclei of posthatch chicks to determine whether a particular subpopulation of neurons is associated with either protein. Moderate levels of parvalbumin immunoreactivity were found consistently associated with repetitively firing neurons in the lateral Edinger Westphal nucleus. In contrast, medial neurons expressed much lower levels of parvalbumin immunoreactivity. Many medial neurons were negative for parvalbumin although occasionally a few medial neurons stained as strongly as lateral neurons. Definitive calbindin immunoreactivity was absent from Edinger Westphal nuclei despite robust staining of cells in other parts of the brainstem and in control sections of cerebellum. PMID- 8481770 TI - Receptive fields of single cells from the face zone of the cat rostral dorsal accessory olive. AB - Natural stimulation was used to map the receptive fields of single cells recorded from the rostral medial portion of the dorsal accessory olive (rDAO) and the subjacent principal olive (PO) of the barbiturate anesthetized cat. Previous reports indicated a somatotopic mapping of the entire contralateral body within the rDAO which included a small face zone and a larger zone with a very precise map for the limbs. While concentrating on the face zone of the rDAO we confirmed the previously reported somatotopy (face: rostral and medial; forelimb: caudal and medial; hindlimb; caudal and lateral; and trunk: rostal and lateral) and found a somatotopy within, and adjacent to, the face zone. At the border between rDAO regions representing forelimb and face, cells with forelimb fields were found to lie dorsally to cells with facial fields. Within the rDAO face region, cells with large facial fields lie dorsally to cells with small facial fields. In both cases, the more ventral cells lie in the ventral lamella of the PO, which suggests a functional as well as physical continuity between rDAO and the ventral lamella of the PO. We therefore conclude that the face zone in the rDAO and the face zone in the PO form one continuous and complete map of the face with an orderly progression of receptive fields. Furthermore, we have found that stimulation of the red nucleus can inhibit rDAO cells with facial receptive fields just as it does cells with receptive fields from the rest of the body. PMID- 8481771 TI - Spatial memory and stereotypic behaviour of animals in radial arm mazes. AB - The symmetric radial arm maze, described by Olton in 1976, has developed into an important tool for the study of spatial memory. In a typical test an animal is placed in the centre of the maze, which contains some small piece of food at the end of each arm. The sampling behaviour of the animal is then recorded. In such studies the score (number of choices of arms which still contain food) of the animal is normally compared with the score of an imaginary animal which changes arms entirely at random. In a new method of analysis the non-random score of the animal is split into two parts, one depending on memory and one on stereotypic choice behaviour. Even mild departures from randomness are shown to alter considerably the expected 'random' score in an eight-armed maze. The part of the score claimed to depend on memory was shown to increase when the animals learn to search the maze, the stereotypic part did not. The general effect from stereotypic choice behaviour is shown to result, in most animals, in an increase in the total score. In an eight-armed maze this increase may amount to more than 20% of the total non-random score, even in a well-trained animal. The effect is less pronounced in mazes with 16 arms. It has been proposed that hippocampal lesions produce a stereotypic behaviour. We propose, based on our analysis, that the stereotypic behaviour is not produced but revealed by hippocampal lesions which destroy almost completely the memory-guided behaviour masking the stereotypic behaviour in the intact animal. PMID- 8481772 TI - Splitting of locomotor circadian rhythmicity in hamsters is facilitated by pinealectomy. AB - The role of the pineal gland in the mammalian circadian system has not been well established, in contrast to a fair number of reports indicating pharmacological effects of melatonin in the circadian organization. In order to establish the effects of pinealectomy on the time course of splitting of circadian rhythmicity, the wheel running locomotor activity was continuously recorded in golden hamsters under light-dark conditions or constant light. The analysis of transients from the actograms shows that removal of the pineal gland induces a reduction in the latency and an increase in the duration of transients before the splitting occurs. The power spectral analysis from selected segments of the data shows that concomitant to the development of the splitting there is an increase in the power of ultradian components. In pinealectomized animals the changes in the power spectrum occurs at least 30 days before that in the control animals. These observations suggest that pineal gland could be involved in the coupling mechanism among the different oscillators of the rodent circadian system. Furthermore, since the light intensity used in this study is enough to completely suppress the melatonin synthesis from the pineal, the present results suggest that a signal from the pineal other than melatonin is involved in the process. PMID- 8481773 TI - Effects of superior olivary complex lesions on binaural responses in rat auditory cortex. AB - Unilateral or bilateral lesions of the superior olivary complex (SOC) were made by local injection of kainic acid through a micropipette lowered stereotaxically into the rat's auditory brain stem. The lesions had the effect of destroying cell bodies in the superior olive without disrupting fibers of passage. After a recovery period of approximately one month physiological recordings were made with tungsten microelectrodes from the auditory cortex of normal animals and animals with SOC lesions. For animals with unilateral SOC lesions recordings were made either ipsilateral or contralateral to the site of damage. Monaural and binaural tone bursts (110 ms duration) were presented dichotically through a sealed sound delivery system and binaural interaction patterns were determined by comparison of monaural and binaural responses. Some cells were excited by stimulation of either ear and facilitated by binaural stimulation (binaural summation or EE cells), whereas others were excited by contralateral stimulation and inhibited by simultaneous ipsilateral stimulation (binaural suppression or EI cells). Both binaural summation and suppression responses were still present following unilateral SOC lesions. Interaural intensity difference thresholds were within the normal range and no differences were found between animals with lesions placed ipsilateral or contralateral to the recording site. Following a bilateral lesion in one case, both binaural summation and suppression responses were still present. The bilateral lesion had the effect of shifting the average interaural intensity difference thresholds in favor of the contralateral ear. These data suggest that binaural interactions above the level of the superior olive contribute to physiological responses in auditory cortex and that binaural responses in the rat's auditory cortex are shaped by both olivary and supraolivary interactions. PMID- 8481774 TI - Long-term increases in the numerical density of synapses in the chick lobus parolfactorius after passive avoidance training. AB - Passive avoidance training has been shown to cause an increase in synaptic density (Nvsyn) in the lobus parolfactorius (LPO) of the one-day old chick. The present study was conducted to investigate the time-course over which this plastic change takes place. Two groups of chicks were trained to peck at either a water coated bead (Control) or a methyl-anthranilate coated bead (M-trained). M trained chicks showed avoidance responses when offered a similar but dry bead, 30 min later. Right and left hemisphere LPOs were obtained at intervals of 1, 6, 12, 24 and 48 h after training. Synaptic counts were made using a 3-dimensional stereological probe; the 'dissector'. A significantly larger mean Nvsyn (31%) was found in the left hemisphere of M-trained chicks 24 h after training, compared with Control chicks, and the difference fell to 10% at 48 h post-training. M trained chicks also had a greater Nvsyn (17%) in the right hemisphere at 48 h post-training. The bilaterality of these findings is of particular interest, since unilateral lesions of the LPO fail to produce amnesia for the avoidance task. The importance of these results in the process of memory formation is discussed. PMID- 8481775 TI - Rod outer segment disk shedding in rats with lesions of the suprachiasmatic nucleus. AB - The suprachiasmatic nucleus (SCN) of the hypothalamus constitutes a major pacemaker for circadian rhythms in mammals. Rod outer segment (ROS) disk shedding follows a circadian rhythm that persists after pre-chiasmatic optic nerve section (ONS) (Teirstein et al., Invest. Ophthalmol. Vis. Sci., 19 (1980) 1268-1273), suggesting local oscillatory control. However, entrainment and phase-shifting to light-dark (LD) cycles are disrupted, suggesting that central efferent signals are involved in phase control. In the present experiment, lesions of the SCN were administered to 45 rats, resulting in complete behavioral arrhythmicity in 24 rats, dampened rhythmicity in 11 rats and robust rhythms in 10 rats. The extent of lesions was verified by histological and immunocytochemical methods. After screening for presence or absence of activity rhythms, rats were assigned to separate groups for ROS disk shedding analysis at four phases relative to the (LD) 12:12 cycle: 1.5 h after light onset, 1.5 h after dark onset, and at corresponding phases immediately upon release into 24 h of constant darkness. The disk shedding pattern, with relatively high phagosome numbers during the early light phase and low numbers at nighttime, was similar for behaviorally arrhythmic, dampened and rhythmic groups. These data indicate an independence of the disk shedding rhythm from possible SCN humoral or neuronal efferent influences. PMID- 8481776 TI - Nucleus ventralis posteromedialis neurons relaying somatosensory lingual input to the cerebral cortex in the cat. AB - The cortical projection of somatosensory lingual units in the nucleus ventralis posteromedialis (VPM) of the thalamus was studied in urethane-chloralose anesthetized cats. Ipsilateral lingual units were recorded from the lateral subdivision of nucleus ventralis posteromedialis parvocellularis (VPMpcl). They were antidromically excited following electrical stimulation of the ventral aspect of the coronal gyrus or its caudally adjacent orbital gyrus. From these same cortical areas, positive surface potentials were recorded following electrical stimulation of the ipsilateral lingual nerve. Electrical stimulation of the same cortical areas elicited jaw opening movement. Contralateral somatosensory lingual units were recorded from the VPM proper. They were antidromically excited following electrical stimulation of the SI somatosensory cortex. PMID- 8481777 TI - [125I]Vasoactive intestinal peptide binding in rodent suprachiasmatic nucleus: developmental and circadian studies. AB - The suprachiasmatic nucleus (SCN) of rat and hamster have been studied extensively and shown to play critical roles in circadian rhythmicity. [125I]Vasoactive intestinal peptide (VIP) binding levels are high in the rat SCN, suggesting that VIP receptors may be an important component of SCN function. In contrast to previously demonstrated diurnal variations in VIP immunoreactivity and VIP mRNA, the present study found [125I]VIP binding to be stable across the light-dark cycle in both rat and hamster SCN. High [125I]VIP labeling appeared to be coextensive with the rat SCN but extended somewhat beyond the cytoarchitectonic boundaries of the hamster SCN. Binding density in hamster SCN was slightly higher than in rat. In the developing rat SCN, [125I]VIP binding levels distinguished the SCN on embryonic day 18, and appeared to increase to postnatal day 10 before declining to adult levels. The early presence of [125I]VIP binding suggests possible involvement of VIP receptors in fetal entrainment of circadian rhythms. PMID- 8481778 TI - Assessing chronic brain damage by quantification of regional volumes in postischemic rat brains. AB - The present study provides data on fresh volumes of 39 anatomically defined brain regions after a 10 min transient forebrain ischemia in the rat. Ischemia was induced by occlusion of the carotid arteries and simultaneous hypotension. After a survival period of 3 months the rats were transcardially perfusion-fixed with Bodian's solution, and the brains processed for paraffin embedding and serially sectioned. The sections were Nissl-stained for delineation of the brain regions. The volume of a brain region was calculated from 8-10 equidistant sections, using the Cavalieri method and corrected for shrinkage of the brain. Fresh volumes were reduced by 27-50% in the layers of the hippocampal CA1 sector, by 40-46% in the substantia nigra, by 19% in the caudate nucleus, by 13% in the subiculum and the cingulate areas 1-3, by 12-14% in the retrosplenial and temporal areas. The results show that determination of fresh volumes is a sensitive method for quantification and localization of ischemic brain damage in the whole brain. PMID- 8481779 TI - Effect of adenosine receptor agonists on spontaneous and K(+)-evoked acetylcholine release from the in vivo rat cerebral cortex. AB - Repeated applications of elevated K+ (100 mM) in artificial cerebrospinal fluid (CSF) were used to evoke an efflux of acetylcholine (ACh) from the in vivo rat cerebral cortex using a cortical cup technique. Elevated K+ reproducibly increased the levels of ACh in cup superfusates by a factor of 3-5-fold above basal levels (27.2 +/- 9.7 nM). The adenosine A1 receptor agonist N6-cyclopentyl adenosine (CPA), at a concentration of 10(-8) M, depressed basal, but not K(+) evoked ACh efflux. 10(-6) M CPA increased basal, but did not alter K(+)-evoked, ACh efflux. The A2 selective agonist CGS 21680 did not alter either basal, or K(+)-evoked, ACh efflux. The inhibitory effects of 10(-8) M CPA on ACh efflux would be consistent with the presence of adenosine A1 receptors on cholinergic nerve terminals in the cerebral cortex. At a higher concentration (10(-6) M) CPA elevated basal release, possibly by activating low affinity A2 receptors. The failure of CGS 21680 (10(-8) M) to alter basal ACh release suggests an absence of high affinity A2 receptors in these terminals. Whereas elevated K+ in cup superfusates consistently enhanced ACh efflux from the cerebral cortex, this increase was not affected by either CPA or CGS 21680. High K(+)-evoked release of cerebral cortical ACh may be an inappropriate model for the study of adenosine's actions on neurotransmitter release. PMID- 8481780 TI - G-protein effects on retrograde axonal transport. AB - Movements of medium and large sized membranous organelles (0.5-1 microns in diameter) were visualized within segments of the crab walking leg nerve with Nomarski differential interference contrast optics and subjected to video contrast enhancement. Accessibility to the axoplasm was demonstrated by intra axonal fluorescence following addition of rhodamine conjugated to 40 kDa dextran to the external medium. Perfusion of the axons with a 1 microM solution of the 20 kDa G-protein, cp20, but not control solutions, reduced the number of organelles moving in the retrograde direction per unit time, but not the number of organelles moving in the anterograde direction. Such alteration of organelle movement may contribute to memory-specific changes of neuronal morphology. PMID- 8481781 TI - Unmasking human visual perception with the magnetic coil and its relationship to hemispheric asymmetry. AB - Visual suppression by a magnetic coil (MC) pulse delivered over human calcarine cortex after a transient visual stimulus 80-100 ms earlier has been used to suppress the representation of a 'masking' visual stimulus and thus to unmask a 'target' visual stimulus given, e.g., 100 ms before the mask. The resulting target unmasking as a function of the interval between mask and MC pulse is approximately the inverse of the visual suppression curve. Arbitrary visual linear patterns can similarly be unmasked. At the long target-mask interval used, the site of masking is deduced to lie beyond calcarine cortex. In several right handed subjects tested, powerful MC stimulation of the left (but not right) temporo-parieto-occipital cortex also led to (weaker) unmasking. PMID- 8481782 TI - Spermine promotes the survival of primary cultured brain neurons. AB - The effects of polyamines on the survival of hippocampal and cerebellar neurons in primary culture were investigated. Putrescine and spermidine showed no effects on the neuronal survival, while spermine increased significantly the number of surviving neurons in both hippocampal and cerebellar cultures. The concentration effect curve for spermine was bell-shaped with the maximum effect at a concentration of 10(-8) M. The survival-promoting effect of spermine was blocked by ifenprodil, an antagonist at the polyamine site of the NMDA receptor channel complex. These results suggest that spermine exerts trophic effects on brain neurons through an ifenprodil-sensitive mechanism. PMID- 8481783 TI - An in vitro study of the effects of methylprednisolone on lesioned and uninjured mammalian spinal neurons. AB - Cultured spinal neurons were subjected to dendrite amputation 100 microns from the perikaryon and treated with methylprednisolone (MP). Survival was significantly increased by 30 micrograms/ml MP but not by 10, 20 or 60 micrograms/ml. Survival was reduced by 100 micrograms/ml MP. These results suggest: (1) MP protects neurons subjected to physical trauma, and (2) the effective dose range is very narrow. These findings may have implications for MP's observed bimodal effects in spinal cord injury. PMID- 8481784 TI - Median preoptic neurons projecting to the hypothalamic paraventricular nucleus are sensitive to blood pressure changes. AB - Twenty-one neurons in the median preoptic nucleus (MnPO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. The activity of these identified neurons was tested for a response to activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous administration of the alpha-agonist metaraminol. Of the neurons tested, 14 displayed a reduction and 2 exhibited an increase in neuronal excitability that accompanied a 30- to 50 mmHg elevation in mean arterial pressure, while 5 were unresponsive. The results show that efferent pathways from the MnPO to the PVN may receive neural inputs from the peripheral baroreceptors, suggesting the involvement of the pathways in the control of cardiovascular function. PMID- 8481785 TI - The effect of halothane dose on striatal dopamine: an in vivo microdialysis study. AB - The relationship between a level of an anesthesia state and striatal dopamine concentration was investigated. The effect of halothane administration on dopamine level in rat striatal extracellular fluid was determined in tracheotomized rats, using an in vivo brain microdialysis method. The striatal dopamine was increased by halothane doses. The correlation coefficient between halothane and dopamine concentrations was 0.69. PMID- 8481786 TI - Effects of ethmoidal nerve stimulation on respiration-related neurones in the dorsal medulla of the cat. AB - Stimulation of the nasal mucosa produces a number of respiratory reflexes the afferent limb of which is provided by the ethmoidal nerve, a branch of the trigeminal nerve. In the cat this nerve terminates within the trigeminal nucleus. It has no direct projection to brainstem respiratory centres. This study examines the response of respiratory-related neurones in the nucleus of the solitary tract (NTS) to ethmoidal stimulation. It demonstrates that these neurones show both excitatory and inhibitory responses to ethmoidal stimulation. Thus, the NTS appears to be involved in respiratory reflexes initiated by stimulation of the nasal mucosa. PMID- 8481787 TI - Activity-dependent expression of the transcription factor Zif268 reveals ocular dominance columns in monkey visual cortex. AB - The visualization of neuronal populations activated by sensory stimulation has been approached using a number of different methodologies. Recent developments in our understanding of transcription factors have provided a new window for observing neural activity. We have found that the transcription factor Zif268 is expressed throughout the visual cortex of the monkey at high basal levels and that monocular visual deprivation produces dramatic changes in its levels revealing ocular dominance columns in striate cortex with as little as 2 h of selective exposure. These results show that immunodetection for Zif268 may be used for labelling activated neuronal populations in the monkey with several key advantages over prior techniques. PMID- 8481788 TI - Protective effects of basic fibroblast growth factor against hippocampal neuronal damage following cerebral ischemia in the gerbil. AB - We examined the effects of treatment with basic fibroblast growth factor (b-FGF) on hippocampal CA1 neuronal damage following 3 min of forebrain ischemia in the gerbil. Continuous infusion of b-FGF (24 or 240 ng/day over 4 days) using an implanted osmotic minipump into the lateral ventricle prevented CA1 neuronal damage in a dose-dependent manner. PMID- 8481789 TI - Naltrexone-induced alterations of the distribution of morphine in brain regions and spinal cord of the rat. AB - The effects of naltrexone injected intravenously (i.v.) on the pharmacological actions and distribution of i.v. injected morphine in brain regions and spinal cord of male Sprague-Dawley rats were determined. Naltrexone (0.625- and 2.5 mg/kg doses) antagonized the analgesic and hyperthermic effects of morphine (10 mg/kg dose). For distribution studies, naltrexone (0.625- and 2.5-mg/kg doses) was co-administered with morphine via indwelling catheters. Rats were sacrificed at various times after drug injection and the concentration of morphine in brain regions (hypothalamus, hippocampus, cortex, pons and medulla, amygdala, midbrain and corpus striatum), spinal cord and serum was determined by radioimmunoassay. The concentration of morphine in various brain regions was found to be time dependent. Initially, at 5 min, the highest concentration of morphine was found in the hypothalamus and the lowest in the striatum. In cortex and spinal cord, the concentration of morphine was significantly higher in comparison to the other brain regions at 30- and 60-min time points. Co-administration of lower dose of naltrexone (0.625 mg/kg) did not significantly alter the distribution of morphine in brain regions and spinal cord with some exceptions. The higher dose of naltrexone (2.5 mg/kg) increased the concentration of morphine in several brain regions and spinal cord. The ratio of the concentration of morphine in brain region or spinal cord to serum was decreased by naltrexone. It is concluded that naltrexone also alters the distribution of morphine in the central nervous system. PMID- 8481790 TI - Insulin and insulin-like growth factor I enhance regeneration in cultured adult rat sensory neurones. AB - Insulin and the insulin-like growth factors (IGFs) may directly affect the growth, development, and maintenance of the vertebrate nervous system. Previous in vitro studies have focused on embryonic nervous tissue. In this study the effects of insulin, IGF-I, IGF-II and nerve growth factor (NGF) on regeneration and neuronal survival were studied in cultured adult rat sensory neurones in a cell culture environment that limited non-neuronal cell mediated effects. Regeneration, as assessed by neurite outgrowth, was significantly enhanced by insulin and IGF-I in a dose-dependent manner. The half-maximally effective concentrations, ED50's, were approximately 1 nM and 0.1 nM for insulin and IGF-I, respectively. Concentrations of IGF-I as low as 10pM were active. There was some evidence that IGF-II stimulated regeneration, although this failed to reach statistical significance. NGF also promoted regeneration, confirming previous studies, exhibiting an ED50 of approximately 0.3 ng/ml and inducing a maximal response 2-fold greater than that observed with insulin or IGF-I. Combined treatment with NGF and insulin had an additive effect. Specific anti-NGF antiserum inhibited the regenerative response to NGF but failed to block the response to IGF-I, supporting the view that IGF-I was acting directly on sensory neurones rather than stimulating NGF production by non-neuronal cells. Insulin, IGF-I and NGF had no effect on neuronal survival in this culture system. These results show that adult sensory neurones can respond with enhanced regenerative growth to insulin and IGF-I, in addition to NGF although the response to IGF-II was less clear. PMID- 8481791 TI - Neurofilaments assume a less random architecture at nodes and in other regions of axonal compression. AB - Neurofilament distributions were mathematically characterized in four chicken somatic motor axons at each of four histologically distinct regions: compact myelinated regions, compact myelinated regions associated with Schwann cell nuclei, Schmidt-Lanterman clefts, and nodes of Ranvier. Compact myelinated regions had the largest cross-sectional areas, the lowest neurofilament densities, and the most random neurofilament organizations--nodes of Ranvier had the smallest cross-sectional areas, the highest neurofilament densities, and the most ordered architectures. In these myelinated axons, the closest natural neurofilament spacing was 25 nm. Mathematical analyses of serial sections suggested that neurofilament interactions are sufficiently weak and transient to permit a full range of variation from random to ordered cytoskeletal architectures as the neurofilaments move longitudinally through the few micron span of the paranodal-nodal region of a single axon. PMID- 8481792 TI - Chronic food restriction and weight loss produce opioid facilitation of perifornical hypothalamic self-stimulation. AB - Electrical stimulation frequency thresholds for lateral hypothalamic (LH) self stimulation were monitored throughout a 3 week period of food restriction and a subsequent 3 week period of re-feeding. Rats with electrodes placed in the perifornical LH were sensitive to this dietary manipulation as evidenced by a high positive correlation between body weight and self-stimulation threshold. Rats with electrodes in the zona incerta/subincertal region or ventral hypothalamus displayed little or no change in threshold. Lateral ventricular injection of naltrexone (200.0 nM) reversed the decline in threshold that was otherwise present during food restriction in rats with perifornical placements. Naltrexone had no effect on thresholds of rats with placements outside the perifornical region. These findings suggest that food restriction and weight loss activate an opioid mechanism that facilitates perifornical LH self-stimulation. The documented association of perifornical LH with the phenomenon of stimulation induced feeding, and the reciprocal connections between this region and gustatory structures, supports the hypothesis that facilitation of self-stimulation by food restriction is related to the natural phenomenon of positive alliesthesia (i.e. the hunger-dependency of food reward). PMID- 8481793 TI - Retinal afferents innervate functionally tectal but not neocortical grafts placed in lesioned superior colliculus of adult rats. AB - Solid pieces of tectum or occipital neocortex derived from 17-day rat fetuses were placed over the lesioned right superior colliculus (SC) in adult rats as sheets retaining the internal structure of the embryonal tissue. The upper laminae of the recipient's SC (approximately up to stratum opticum) were removed by aspiration after the neocortex overlying the SC was aspirated out. Two to 5 months after the operation a microelectrode study of the neuronal electrical activity in the grafts was performed. Recordings from the tectal transplants revealed normal patterns of the spontaneous neuronal activity in all grafts and clear neuronal reactions to visual stimuli in a large portion of them (6 out of 11). Visual reactions in these grafts were recorded from the majority of studied neurons (185/226). The properties of the receptive fields as well as the range of latencies of the reactions corresponded to those characteristic of the normal SC. Topographic representation of the visual field upon the transplants was found. Recordings from the cortical grafts showed an abnormal character of the spontaneous neuronal activity and the absence of reactions to any sensory stimulation of the recipients. The data obtained suggest that regenerating optic axons in adult hosts retain specificity in functional innervation of only appropriate target neurons and can re-establish the topographic representation of the retina upon tectal grafts. Retinal afferents innervate functionally tectal but not neocortical grafts placed in lesioned superior colliculus of adult rats. PMID- 8481794 TI - Opioid-induced inhibition of voltage-gated calcium channels parallels expression of omega-conotoxin-sensitive channel subtype during differentiation of NG108-15 cells. AB - Depolarization-induced increases in intracellular free calcium concentration ([Ca2+]i) were measured in single NG108-15 cells using indo-1 based microfluorimetry. In cells differentiated for 6 days in serum-free forskolin (5 microM) supplemented media, application of micromolar concentrations of [D-Ala2-D Leu5]enkephalin (DADLE) inhibited Ca2+ influx mediated by voltage-gated Ca2+ channels. Inhibition of 50 mM K(+)-induced Ca2+ influx by DADLE was concentration dependent over the range of 0.1 to 10 microM and blocked by 100 microM naloxone. Differentiation increased the amplitude of depolarization-induced [Ca2+]i transients from 78 +/- 21 nM in undifferentiated cells to 1,282 +/- 318 nM after 6 days. One microM nitrendipine inhibited Ca2+ influx by at least 65% at all stages of differentiation, while sensitivity to omega-conotoxin GVIa (omega-CgTx) did not appear until day 3. omega-CgTx inhibited a dihydropyridine-sensitive Ca2+ channel. DADLE inhibition of Ca2+ channels did not appear until 3 days of differentiation. Thus, opioid inhibition of depolarization-induced Ca2+ influx paralleled the expression of omega-CgTx sensitive voltage-gated Ca2+ channels. PMID- 8481795 TI - Potentiation by choline of basal and electrically evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum. AB - We examined the release of acetylcholine (ACh) and dopamine (DA) using a novel probe through which striatal neurons could be both superfused and stimulated electrically in both anesthetized and freely moving awake animals. Optimal stimulation parameters for eliciting ACh release from cholinergic neurons differed from those required for eliciting DA release from dopaminergic terminals: at 0.6 ms pulse duration, 20 Hz and 200 microA, ACh release increased to 357 +/- 30% (P < 0.01) of baseline and was blocked by the addition of tetrodotoxin (TTX). Pulse durations of 2.0 ms or greater were required to increase DA release. Unlike ACh release, DA release showed no frequency dependence above 5 Hz. The maximal evoked releases of ACh and DA were 556 +/- 94% (P < 0.01) and 254 +/- 38% (P < 0.05) of baseline, respectively. Peripheral administration of choline (Ch) chloride (30-120 mg/kg) to anesthetized animals caused dose-related (r = 0.994, P < 0.01) increases in ACh release; basal release rose from 117 +/- 7% to 141 +/- 5% of initial baseline levels (P < 0.05) and electrically evoked ACh release rose from 386 +/- 38% to 600 +/- 34% (P < 0.01) in rats given 120 mg/kg. However, Ch failed to affect basal or evoked DA release although neostigmine (10 microM) significantly elevated basal DA release (from 36.7 fmol/10 min to 71.5 fmol/10 min; P < 0.05). In awake animals, Ch (120 mg/kg) also elevated both basal (from 106 +/- 7% to 154 +/- 17%; P < 0.05) and electrically evoked (from 146 +/- 13 to 262 +/- 16%; P < 0.01) ACh release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481796 TI - C-fos expression in rat lumbar spinal cord following peripheral stimulation in adjuvant-induced arthritic and normal rats. AB - Our previous data reported a maximal expression of the c-fos immediate-early gene in the lumbar spinal cord of the non-stimulated polyarthritic rat neurons, three weeks after Freund's adjuvant injection. The present study utilises c-fos expression to judge the reactivity of spinal neurons to calibrated mechanical pressure applied to the ankle joint, in both normal and arthritic rats under ketamine anesthesia. The results indicate that the number of Fos-like immunoreactive neurons (1) is slightly decreased in ketamine-anesthetized non stimulated arthritic rats as compared to the non-anesthetized non-stimulated ones, (2) is significantly higher in both stimulated normal and arthritic animals as compared to non-stimulated animals, particularly in laminae I, II, V and VI of L3 and L4, and (3) is significantly increased in stimulated arthritic as compared to stimulated normal rats, in all laminae of lumbar spinal segments. The appearance of 'basal' Fos labeling during the adjuvant-induced arthritic disease and the increased number of Fos-like immunoreactive neurons in stimulated arthritic rats compared to stimulated normal animals indirectly suggests that these neurons are abnormally active and thus involved in the hyperalgesia of arthritic disease. Therefore the use of Fos-like immunoreactivity in the chronic pain model seems to be an appropriate tool to study possible effects of various pharmacological compounds, such as analgesics and anti-inflammatory drugs. PMID- 8481797 TI - Neurochemical evidence that 5-hydroxytryptaminergic neurons tonically inhibit noradrenergic neurons terminating in the hypothalamus. AB - The medial zona incerta (MZI) and dorsomedial nucleus of the hypothalamus (DMN), which contain cell bodies and terminals of incertohypothalamic dopaminergic (DA) neurons, are densely innervated by both noradrenergic (NE) and 5 hydroxytryptaminergic (5-HT) neurons. In view of emerging anatomical and pharmacological evidence suggesting possible interactions between 5-HT and catecholaminergic neurons, the effects of experimental procedures that inhibit or disrupt 5-HT neurons on the activities of catecholaminergic neurons terminating in these regions were examined in the present study. Catecholaminergic neuronal activity was estimated by measuring catecholamine synthesis (accumulation of 3,4 dihydroxyphenylalanine [DOPA] after administration of a decarboxylase inhibitor) and metabolism (concentrations of the dopamine metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) and the norepinephrine metabolite 3-methoxy-4 hydroxyphenylethyleneglycol (MHPG)) in the MZI and DMN of both male and female rats. Inhibition of 5-HT neurons following administration of the 5-HT1A autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increased the accumulation of DOPA in the DMN and the concentrations of DOPAC in the MZI and DMN, indicating an activation of catecholaminergic neurons in these regions. Concentrations of MHPG were increased in the MZI and DMN by 8-OH-DPAT or 5,7 dihydroxytryptamine-induced lesions of 5-HT neurons, revealing that NE neurons terminating in these regions were activated following procedures that decrease 5 HT neuronal function. Following destruction of NE neurons projecting to the MZI and DMN, 8-OH-DPAT no longer increased DOPAC concentrations in these brain regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481798 TI - [3H]phorbol ester binding sites and neuronal plasticity in the hippocampus following entorhinal cortex lesions. AB - Entorhinal cortex lesioning (ECL) produces a loss of more than 80% of the synapses in the outer molecular layer of the hippocampus. However, the loss of synapses is transient. Beginning a few days after denervation, new synapses are formed, virtually replacing the lost inputs within 2 months. Synaptic remodelling induced by ECL is associated with specific modifications of neurotransmitters, hormones and growth factors. Particularly, protein kinase C (PKC) plays important functional roles in receptor-mediated transmembrane signal transduction. PKC is also involved in various aspects of synaptic plasticity, such as cellular growth and differentiation. To investigate further the potential roles of PKC in synaptic plasticity observed in the ECL model, [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding, a putative marker of PKC, was examined at different times post-lesion. [3H]PDBu binding sites transiently decreased bilaterally at 2 and 8 days post-lesion (20%) in different laminae and sub-fields of the rostral hippocampus but returned to control values at 14 and 30 days post-lesion. In caudal portion of the hippocampus, [3H]PDBu binding was also decreased at 2 days post-lesion but only on the contralateral side. Interestingly, [3H]PDBu binding sites in the cortex increased by up to 30% in the contralateral side while no significant change was observed in the ipsilateral side at any time post-lesion. It is known that PKC can be regulated by different systems following alterations of neuronal and glial activity. We suggest that these could be involved in the response of PKC and [3H]PDBu binding sites following ECL. Moreover, PKC seemed to be modified in different brain areas in neuronal inputs from the entorhinal cortex and the subsequent reinnervation process. PMID- 8481799 TI - Pituitary gland responsiveness to LHRH and LHRH neuronal responsiveness to excitatory stimuli are severely impaired in female rats treated neonatally with high doses of androgen. AB - Treatment of neonatal female rats with androgen renders these animals permanently sterile as adults. Previously, we reported that these androgen-sterilized rats (ASR) do not respond to the positive feedback effects of estrogen by having LH surges. We also reported that this defect might be due to the failure of these animals to show increased hypothalamic norepinephrine turnovers (an index of secretion) in response to steroid treatment. Although LHRH-catecholamine synapses are established before or at birth, whether such synapses are functional remains to be resolved. Accordingly, in the present studies, female rats were given 1.25 mg of testosterone propionate at 5 days of age and, at 100 days of age, these ASR and controls were ovariectomized and treated with estradiol. In these animals, we examined whether activation of medullary A1 noradrenergic neurons would amplify LH release following preliminary depolarization of LHRH neurons with an electrochemical stimulus (ECS). As well, we reexamined whether LHRH neuronal responsiveness to exogenous NE and pituitary responsiveness to LHRH differ in controls versus ASR. In controls, two pulses of LHRH given 60 min apart elicited increases in plasma LH with the second pulse inducing greater LH release than the first pulse. In ASR, significantly less LH was released after either LHRH pulse and particularly after the second pulse. When the spacing between the two LHRH pulses was reduced to 25 min, equivalent levels of LH release occurred in controls and ASR after the second pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481800 TI - Cellular and intracellular localization of epsilon-subspecies of protein kinase C in the rat brain; presynaptic localization of the epsilon-subspecies. AB - The cellular and intracellular localization of the epsilon-subspecies of protein kinase C (PKC) in the rat brain was demonstrated by immunocytochemistry using specific antibodies against epsilon-PKC. The epsilon-PKC-specific immunoreactivity was most abundant in the hippocampal formation, olfactory tubercle and Calleja's islands, was moderate in the cerebral cortex, anterior olfactory nuclei, accumbens nucleus, lateral septal nuclei and caudate-putamen and low in the thalamus and medulla. The epsilon-PKC-immunoreactivity was scanty in the perikarya, except for the pyramidal cells of CA3 region of the hippocampus and the immunoreactivity was mainly present in neuropils and nerve fibers. The distribution of epsilon-PKC immunoreactive neurons was consistent with that obtained by in situ hybridization histochemistry. Electron microscopic observations of the hippocampus revealed that the epsilon-PKC is predominantly present in the cytoplasm of axon and nerve terminals and that this enzyme is associated with mitochondrial membrane and vesicles. These results suggested that epsilon-PKC is probably involved in presynaptic functions in CNS, perhaps even neurotransmitter release. PMID- 8481801 TI - A novel stretch receptor in the jaw of the rat. AB - We report here an unusual type of stretch receptor found on each side of the rat jaw. This receptor has unique morphological features: it is quite long (24-28 mm), lies in connective tissue in between masticatory muscles, and extends between the medial pterygoid muscle-tendon on the maxilla and the masseter-tendon on the mandible through a zigzag course, forming a Greek capital letter sigma when viewed from the side. The receptor is neither in parallel nor in series with any masticatory muscles and receives multiple innervation. The receptor increases its length when the jaw closes and shortens when the jaw opens. Electron microscopy revealed axial structures composed of a central cellular core surrounded by tightly packed collagen bundles which are separated from the capsule by a wide capsular space. Most of the sensory endings are found among axial collagen bundles, some in between core cells. The core cells have many finger-like processes on their surface, being coupled by desmosomes. The origin and nature of these cells are unclear. The wide capsular space is filled with Alcian blue positive substrate, probably acid glycosaminoglycans. The structures of outer and inner capsules are similar to those of muscle spindles, the former being composed of three to ten layers of thin flattened cells. The response of the receptor was examined with in vivo as well as in vitro preparations. In in vivo experiments, impulse discharges from this receptor increased with the increase in jaw closing. When the jaw was fully opened the impulse discharge from this receptor disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481802 TI - D1 dopamine agonist and antagonist effects on regional cerebral glucose utilization in rats with intact dopaminergic innervation. AB - The effects of stimulation and blockade of the D1 dopamine receptor on regional cerebral glucose utilization (RCGU) were studied using quantitative [14C]2 deoxyglucose autoradiography in naive rats. Systemic administration of the selective D1 antagonist, SCH 23390 (0.5 mg/kg), lowered glucose utilization by 24 28% in the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra pars reticulata (SNr), and motor cortex, suggesting that stimulation of the D1 receptor by endogenous dopamine contributes to basal metabolism in these regions. Administration of SCH 23390 increased RCGU in the lateral habenula, as do selective D2 antagonists. The selective D1 agonist, SKF 38393 (30 mg/kg), increased RCGU in the SNr (up 22%) without affecting the other brain regions which were examined. This modest increase contrasts with the large increase in RCGU (up 100-200%) in the SNr elicited by similar doses of SKF 38393 in rats with acute or chronic dopamine depletion. Systemic administration of amphetamine (5.0 mg/kg), a dopamine releasing agent, increased RCGU in the caudate-putamen (up 33%), globus pallidus (up 23%), subthalamic nucleus (up 46%), entopeduncular nucleus (up 78%), and SNr (up 72%) and lowered RCGU in the lateral habenula (down 43%). All of these amphetamine effects were blocked by pretreatment with either SCH 23390 (0.5 mg/kg) or eticlopride (2.0 mg/kg, a selective D2 antagonist). These results suggest that endogenous dopamine stimulates both D1 and D2 receptors in vivo and provide metabolic evidence to support the concept of a functional linkage of D1 and D2 receptor systems in animals with intact dopaminergic innervation. PMID- 8481803 TI - Aging alters the entraining effects of an activity-inducing stimulus on the circadian clock. AB - In young hamsters, a single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian clock, while repeated injections of triazolam entrain the circadian clock to the period of the injections. Triazolam appears to act on the circadian clock by inducing an acute increase in the activity of the animals, which in turn phase-shifts the circadian clock. Surprisingly, single injections of benzodiazepines do not phase-shift the activity rhythm of old hamsters, despite the fact that such treatment induces similar acute changes in the activity state of young and old animals. We compared the entraining effects of repeated injections of triazolam on the circadian clock of young and old hamsters; while six out of seven young hamsters were entrained to the triazolam injections, only one out of seven old animals was entrained by this treatment. Three of the remaining six old hamsters showed a lengthening of the activity rhythm, while no consistent effect on the period of the activity rhythm was observed in the remaining three old animals. These results indicate that the circadian system of old hamsters becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state, and suggest that aging is associated with a weakened coupling between the activity-rest cycle and the circadian clock. PMID- 8481804 TI - Evidence for the behavioral supersensitivity of dopamine D2 receptors without receptor up-regulation in morphine-abstinent rats. AB - The effect of morphine tolerance-dependence and abstinence on the characteristics of dopamine D2 receptors in brain regions and spinal cord was determined in the rat. Male Sprague-Dawley rats were implanted s.c. under light ether anesthesia with 6 morphine pellets for a 7-day period, each containing 75 mg of morphine free base. Rats implanted with placebo pellets served as controls. This procedure resulted in the development of tolerance to morphine as evidenced by decreased analgesic response to a challenge dose of morphine. Similarly, the development of physical dependence was evidenced by a decrease in body weight and colonic temperature after morphine pellet removal (withdrawal). The binding characteristics (Bmax and Kd values) of [3H]spiroperidol to dopamine D2 receptors were determined in the tissues of morphine-tolerant and morphine-abstinent rats. In the tolerant rats, the pellets were left intact at the time of sacrificing, whereas, in the abstinent rats the pellets were removed 18 h prior to sacrificing. The binding of [3H]spiroperidol was determined in membranes prepared from brain regions (hypothalamus, hippocampus, cortex, pons and medulla, midbrain, corpus striatum and amygdala) and spinal cord of rats from various treatment groups. [3H]Spiroperidol bound to brain regions and spinal cord at a single high affinity site. The Bmax or the Kd values in brain regions and spinal cord of morphine-tolerant and -abstinent rats did not differ from their respective placebo controls. The behavioral responses to a selective dopamine D2 receptor agonist, 2-bromo-alpha-ergocryptine were also determine in the morphine abstinent rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481805 TI - Neurofilament in feline primary afferent neurones: a quantitative immunocytochemical study. AB - Two populations of cat L4 dorsal root ganglion (DRG) neurones were apparent from their Nissl staining with Toluidine blue. One had neurones of all sizes and the other had predominantly small neurones. The size distribution of neuronal profiles in the two populations overlapped and both were approximately normal. They corresponded to the light (L) and small dark (SD) cell populations previously described in rat DRGs. These neurones were examined with four antibodies to neurofilament: RT97, NFH, 155 and anti-68kD. RT97 is specific for the phosphorylated form of the 200 kDa subunit; NFH recognises both phosphorylated and non-phosphorylated forms of this subunit; 155 and anti-68 kDa recognise the 155 kDa and 68 kDa subunits respectively. The clearest differential labelling was seen with NFH and RT97 and this labelling was compared with cell size. High intensity NFH labelling was in a population of neuronal profiles of all sizes and low intensity labelling in a population of predominantly small neuronal profiles. These populations corresponded respectively to the L and SD populations seen with toluidine blue staining. In the rat, these populations can be demonstrated by both NFH and RT97. In contrast in the cat, high intensity RT97 labelling was seen in only 75% of the L neuronal profiles defined with NFH and was also seen in some SD neuronal profiles defined with NFH. It is thus proposed that L and SD cell types are present in the cat DRG and can be demonstrated using the anti-neurofilament marker, NFH. PMID- 8481806 TI - Morphine inhibits antidromic vasodilatation without affecting the excitability of C-polymodal nociceptors in the skin of the rat. AB - The effect of morphine was examined under identical conditions on (a) antidromic vasodilatation, an 'efferent' function of C-nociceptors in the skin, and (b) afferent responses to heat and pressure of C-polymodal nociceptors. Morphine caused a large, naloxone-reversible, fall in peak antidromic vasodilatation (ADV). However it caused no significant change in heat or mechanical excitability of C-polymodal nociceptors in normal or mildly inflamed skin. The mechanisms by which morphine might affect efferent, but not afferent, functions of C nociceptors are discussed. PMID- 8481807 TI - Selective alteration in B-50/GAP-43 phosphorylation in brain areas of animals characterized by cognitive impairment. AB - When methylazoxymethanol acetate is administered to pregnant rats at gestational day 19, the offspring are greatly impaired in the learning of a two-way active avoidance task and these behavioral changes are paralleled by a change in the phosphorylation of the protein B-50/GAP-43 in hippocampus but not in cortex. The expression of the protein is not altered, indicating that the phosphorylation of B-50 is a sensitive marker of alterations in synaptic plasticity associated with impairments of learning abilities in rats. PMID- 8481808 TI - Auditory sensory gating in the rat hippocampus: modulation by brainstem activity. AB - Auditory stimuli repeated at short intervals result in diminished evoked responses recorded from the skull surface and from the hippocampus in the rat. The rat has been used to model diminished responses to repeated auditory stimuli- a phenomenon seen in normal human subjects, but often absent in schizophrenics. In this study, we examined the neural circuitry involved in the processing and gating of auditory responses recorded from the hippocampus of the rat. Evoked potentials and single neuron activity with diminished responses to the second of paired tones were recorded in the brainstem reticular formation in the paragigantocellular region at the caudal level of the pons, but diminished responses were not observed in the primary auditory relay nuclei. Electrical stimulation of this region of the brainstem reticular formation was able to substitute for the first, or conditioning, auditory tone to produce sensory gating of the response to the second, or test, tone when recording from the hippocampus. Stimulation of the auditory nuclei up to the level of the lateral lemniscus, but not the superior colliculus, was also able to substitute for an auditory stimulus to produce sensory gating in the hippocampus. The gating of hippocampal responses to auditory stimuli may thus involve pathways which branch from the lemniscal auditory pathway at the level of the lateral lemniscus and ascend to the hippocampus via the brainstem reticular formation. PMID- 8481809 TI - Gender influences outcome of brain injury: progesterone plays a protective role. AB - The contributions of gender and gonadal hormones in the cascade of events following brain injury are largely unexplored. We measured cerebral edema following cerebral contusion in rats under three hormonal conditions to address this issue. Normally cycling females exhibited significantly less edema than males, and pseudopregnant females were virtually spared from post-injury edema. Subsequent studies of ovariectomized females, with or without hormone treatment, indicated that the reduction of cerebral edema was associated primarily with the presence of circulating progesterone. We conclude that progesterone has a protective effect on the brain following traumatic injury. PMID- 8481810 TI - Effect of varying levels of glucose on oxygen deprivation-induced delayed neuronal cell death in primary cerebrocortical cultures. AB - Calcium accumulation and neuronal injury of rat cortical cell cultures in vitro were examined following oxygen deprivation under conditions of normal and low glucose. 45Ca2+ uptake and lactate dehydrogenase (LDH) release, measured at 12 and 24 h after oxygen deprivation, were significantly elevated in cultures exposed to combined oxygen deprivation and low glucose (1.7 or 0.6 mM). Although those cultures deprived of oxygen combined with no glucose displayed delayed increases in 45Ca2+ influx, no significant elevation in LDH release at 24 h was observed. PMID- 8481811 TI - ATP mediates an excitatory noradrenergic neuron input to supraoptic vasopressin cells. AB - Although A1 noradrenaline (NA) neurons of the caudal medulla provide a direct, excitatory input to supraoptic vasopressin cells, they do not use NA as their primary transmitter. We have now tested the possibility that adenosine 5' triphosphate (ATP) may fulfill this role. Extracellular recordings from rat supraoptic nucleus demonstrated that locally applied ATP excites neurosecretory vasopressin cells and that this effect is mimicked by the ATP receptor-agonist alpha,beta-methylene ATP and blocked by the ATP receptor-blocker suramin. Suramin did not block the excitatory effect of locally applied NA on vasopressin cells but did block excitations produced by vagus nerve stimulation, such excitations having previously been shown to involve a pathway in which the final relay is an input from the A1 cell group. These results indicate that certain central NA neurons use ATP as a transmitter and also provide the first demonstration of a specific physiological role for central purinergic neurons, i.e. regulation of secretion of the neurohormone vasopressin. PMID- 8481812 TI - Pulmonary and upper airway afferent influences on the motor pattern of vocalization evoked by excitation of the midbrain periaqueductal gray of the cat. AB - It has been established previously that natural-sounding vocalization is evoked by excitation of the midbrain periaqueductal gray (PAG). It is not known, however, whether the motor output for such vocalization is invariant, or whether it is influenced by afferent discharge. We have investigated, in the unanesthetized precollicular decerebrate cat, the patterns of upper airway and respiratory EMG activity evoked by microinjection into the PAG of the excitatory amino acid D,L-homocysteic acid (6 to 40 nmol in 30-200 nl), under conditions of varied pulmonary and upper airway afferent input. The PAG-evoked pattern in the control state consisted of a 1- to 2-min sequence of episodic vocalizations (hiss or howl-like) with expiratory (vocalization) durations of generally less than 2 s, separated by one or more inspirations. During such PAG-evoked vocalization, a significant prolongation of the expiratory duration and an extended discharge in laryngeal, intercostal and abdominal muscles was evoked by the application of warm, humidified static air pressures (5-30 cm H2O) either: (i) to the lungs and tracheo-bronchial tree via a tracheostomy, or (ii) as an airflow through the upper airways in an expiratory direction. In contrast, if the development of the usual vocalization-related air pressures (5-45 cm H2O) in the lungs and airways was prevented by opening a tracheal cannula to the atmosphere, shortened respiratory durations (inspiratory and expiratory) occurred. The effects evoked by static pressure inflations of the lungs could be blocked by bilateral vagotomy or reversibly blocked by unilateral vagotomy combined with vagal cooling sufficient to abolish Hering-Breuer reflexes. These results indicate that the motor pattern for vocalization evoked by excitation of PAG is exquisitely sensitive to pulmonary and upper airway afferent input. PMID- 8481813 TI - Inhibition of NMDA-evoked electrophysiological activity by ethanol in selected brain regions: evidence for ethanol-sensitive and ethanol-insensitive NMDA-evoked responses. AB - Our laboratory has previously shown that systemically administered ethanol inhibits NMDA-evoked electrophysiological activity in some, but not all, neurons in the medial septum. In the present report, it was found that ethanol, when applied locally via electro-osmosis, potently inhibited NMDA-evoked neuronal activity in a current-dependent manner in the inferior colliculus and hippocampus. In contrast, locally applied ethanol failed to inhibit NMDA-evoked activity in the lateral septum. The inhibition by ethanol of NMDA-evoked activity in the inferior colliculus was specific, in that ethanol failed to inhibit neuronal activity of the inferior colliculus evoked by the excitatory neurotransmitter glutamate. These findings indicate that ethanol can specifically inhibit NMDA-evoked activity in vivo via a local action, and that the ability of ethanol to inhibit NMDA-evoked activity varies regionally in brain. The possibility that these results are explained by the existence of two types of NMDA receptors, one sensitive to ethanol, the other insensitive to ethanol, is discussed. PMID- 8481814 TI - A robust, high-sensitivity algorithm for automated detection of proteins in two dimensional electrophoresis gels. AB - The automated interpretation of two-dimensional gel electrophoresis images used in protein separation and analysis presents a formidable problem in the detection and characterization of ill-defined spatial objects. We describe in this paper a hierarchical algorithm that provides a robust, high-sensitivity solution to this problem, which can be easily adapted to a variety of experimental situations. The software implementation of this algorithm functions as part of a complete package designed for general protein gel analysis applications. PMID- 8481815 TI - Prediction of protein secondary structure by the hidden Markov model. AB - The purpose of this paper is to introduce a new method for analyzing the amino acid sequences of proteins using the hidden Markov model (HMM), which is a type of stochastic model. Secondary structures such as helix, sheet and turn are learned by HMMs, and these HMMs are applied to new sequences whose structures are unknown. The output probabilities from the HMMs are used to predict the secondary structures of the sequences. The authors tested this prediction system on approximately 100 sequences from a public database (Brookhaven PDB). Although the implementation is 'without grammar' (no rule for the appearance patterns of secondary structure) the result was reasonable. PMID- 8481816 TI - Prediction of protein secondary structures by a neural network. AB - We have studied the prediction of globular protein secondary structures by neural networks. Protein secondary structures are allocated to amino acid residues using Kabsch and Sander's dictionary of protein secondary structures and the neural network is taught the protein secondary structures. The input layer of the neural network allows sequences of residues including 20 amino acids, chain break, B, X and Z. We consider classifying secondary structures into groups of 3, 4 and 8. In each case, we calculate the percentage of correct predictions. We discuss the effect of overlearning on the protein secondary structure prediction. In addition, we include the application of a neural network with a modular architecture to prediction of protein secondary structures. We compare the results from neural networks with a modular architecture and with a simple three layer structure. PMID- 8481817 TI - An approach to systematic detection of protein structural motifs. AB - A procedure to detect similar local structures of proteins from C alpha coordinates is presented. First, the conformations of seven-residue peptide segments are approximated by a limited number of representatives, each of which is assigned a symbol. Thus, the overall conformation of a protein is represented by a symbol string. The comparison of these symbol strings using a sequence alignment technique then gives pairs of similar local structures. These pairs are considered candidates of structural motifs. The application of the procedure to the analysis of 93 proteins gave 858 pairs of similar local structures, which included several well-known structural motifs such as the nucleotide-binding beta alpha beta-unit and the calcium-binding EF hand. The characterization of amino acid patterns of similar local structures given by the procedure should be useful for the development of protein structure prediction based on the acquisition of empirical rules from a large-scale database. PMID- 8481818 TI - MASCOT: multiple alignment system for protein sequences based on three-way dynamic programming. AB - A multiple alignment methodology that can produce high-quality alignment is extremely important for predicting the structure of unknown proteins. Nearly all the methodologies developed so far have employed two-way alignment only. Although these methods are fast, the alignments they produce lose reliability as the similarity of sequences reduces. We developed the MASCOT multiple alignment system. MASCOT can sustain the reliability of alignment even when the similarity of sequences is low. MASCOT achieves high-quality alignment by employing three way alignment in addition to two-way alignment. The resultant alignments are refined by simulated annealing to higher quality. We also use a cluster analysis of sequences to produce highly reliable alignments. PMID- 8481819 TI - Building multiple alignments from pairwise alignments. AB - Given a family of related sequences, one can first determine alignments between various pairs of those sequences, then construct a simultaneous alignment of all the sequences that is determined in a natural manner by the set of pairwise alignments. This approach is sometimes effective for exposing the existence and locations of conserved regions, which can then be aligned by more sensitive multiple-alignment methods. This paper presents an efficient algorithm for constructing a multiple alignment from a set of pairwise alignments. PMID- 8481820 TI - TREECON: a software package for the construction and drawing of evolutionary trees. AB - A package of programs (run by a management program called TREECON) was developed for the construction and drawing of evolutionary trees. The program MATRIX calculates dissimilarity values and can perform boostrap analysis on nucleic acid sequences. TREE implements different evolutionary tree constructing methods based on distance matrices. Because some of these methods produce unrooted evolutionary trees, a program ROOT places a root on the tree. Finally, the program DRAW draws the evolutionary tree, changes its size or topology, and produces drawings suitable for publication. Whereas, MATRIX is suited only for nucleic acids, the modules TREE, ROOT and DRAW are applicable to any kind of dissimilarity matrix. The programs run on IBM-compatible microcomputers using the DOS operating system. PMID- 8481821 TI - A fast, sensitive pattern-matching approach for protein sequences. AB - Pattern-matching algorithms are a powerful tool for finding similarities and relationships among the steadily growing amount of known protein sequences. We present a fast, sensitive pattern-matching algorithm that describes a pattern by its physico-chemical properties rather than by occurrence of amino acids, using a fast, dynamic programming algorithm. Selected examples will demonstrate applications and advantages of our approach. PMID- 8481822 TI - Dot-plot comparisons by multivariate analysis (DOCMA): a tool for classifying protein sequences. AB - A method aimed at classifying protein sequences without resorting to pairwise alignment is presented. Called DOCMA (DOt-plot Comparisons by Multivariate Analysis), it is based on a multivariate analysis of the pairwise dot-plots between all the sequences in the set. The dot-plots are first simplified by considering only the projections of the 'diagonal' segments of similarity onto the axes. From these projections a data matrix is built, in which each column is representative of the comparisons of one given sequence with all the other ones. This data matrix is then transformed into a distance matrix by a chi-squared analysis, from which the coordinates of the sequences in an orthonormal Euclidean space are obtained. The sequences are finally classified by a dynamic clustering procedure followed by a search for strong clusters. Application of this method to protein families such as the globins, the cytochromes c and the aminoacyl-tRNA synthetases shows that it is quite effective in delineating subgroups that contain even distantly related sequences. PMID- 8481823 TI - An interactive graphic program for calculating the secondary structure content of proteins from circular dichroism spectrum. AB - A graphic program has been developed to calculate the secondary structure content of proteins from their circular dichroism spectrum. All the information concerning analysis and results are given on a single screen. The actual and the theoretical spectra are plotted to allow visual inspection of the fit quality. The percentages of secondary structure and statistical parameters (r.m.s., residuals) are provided. The program is fully interactive for spectra analysis. Moreover, cursors driven by a mouse or arrow keys are moveable onto spectra yielding all the information concerning a given wavelength, such as the theoretical and experimental ellipticities, wavelength, values of reference model for alpha-helix, beta-sheet and beta-turn. Interfaces are provided for the CONTIN program of Provencher and Glockner. PMID- 8481824 TI - PCAP: probe choice and analysis package--a set of programs to aid in choosing synthetic oligomers for contig mapping. AB - In the program, PCAP, we provide a methodology for choosing synthetic oligonucleotide probes to be used in contig mapping experiments. The package serves the purpose of presenting a series of short oligonucleotides (8-12mers) that are chosen based on constraints with respect to frequency of occurrence within a particular genome and the G+C content of the oligonucleotides. The four programs contained within the package: (i) convert GenBank files to a format useable by the package; (ii) calculate trinucleotide and tetranucleotide frequencies in available sequence data on a particular species; (iii) present the user with upper and lower bounds on the frequencies of hybridization sites for oligonucleotide probes of length 8-12, (iv) allow the user to place constraints on site frequency and G+C content and provides a list of short probe sequences that fit these criteria. These sequences can then be synthetically produced and used in hybridization experiments to carry out contig mapping. PMID- 8481825 TI - Classification of protein sequences by their dipeptide composition. AB - A simple approach to scan quickly a large protein sequence database for homology is described. The approach used is strictly dependent on the database organization. A database has been compiled in which protein sequences are grouped into families of closely related proteins, each family being characterized by its average dipeptide composition. A new entry in the database can be allocated in a family by comparing its dipeptide composition with the average dipeptide composition of the families. PMID- 8481826 TI - A hypertext-like approach to navigating through the GCG sequence analysis package. AB - Programs of the recently released Unix version of the Genetics Computing Group (GCG) sequence analysis package can now be accessed via a user-friendly hypertext like navigation system, HYGCG. The resultant system organizes the diverse suite of programs into logical groups, and provides a guide and explanation of commands. In addition, for users unfamiliar with the Unix operating system, the program also provides a similar interface to commonly used Unix commands. Options for personal customization and expansion to accommodate GCG extensions and other software are also provided. This system should be useful especially to the inexperienced or infrequent user as context-sensitive on-line help is provided within this simple and consistent approach. Written in the C language and using the curses and termcap libraries, the system is easily portable to most Unix environments and has been made freely available via anonymous file transfer protocol (FTP) through the Internet global computer network. No modification of the GCG package is needed. PMID- 8481827 TI - ODS: ordering DNA sequences--a physical mapping algorithm based on simulated annealing. AB - In the program ODS we provide a methodology for quickly ordering random clones into a physical map. The process of ordering individual clones with respect to their position along a chromosome is based on the similarity of binary signatures assigned to each clone. This binary signature is obtained by hybridizing each clone to a panel of oligonucleotide probes. By using the fact that the amount of overlap between any two clones is reflected in the similarity of their binary signatures, it is possible to reconstruct a chromosome by minimizing the sum of linking distances between an ordered sequence of clones. Unlike other programs for physical mapping, ODS is very general in the types of data that can be utilized for chromosome reconstruction. Any trait that can be scored in a presence--absence manner, such as hybridized synthetic oligonucleotides, restriction endonuclease recognition sites or single copy landmarks, can be used for analysis. Furthermore, the computational requirements for the construction of large physical maps can be measured in a matter of hours on work-stations such as the VAX2000. PMID- 8481828 TI - A special-purpose processor for gene sequence analysis. AB - Advances in computational biology have occurred primarily in the areas of software and algorithm development; new designs of hardware to support biological computing are extremely scarce. This is due, we believe, to the presence of a non trivial knowledge gap between molecular biologists and computer designers. The existence of this gap is unfortunate, as it has long been known that for certain problems, special-purpose computers can achieve significant cost/performance gains over general-purpose machines. We describe one such computer here: a custom accelerator for gene sequence analysis. The accelerator implements a version of the Needleman-Wunsch algorithm for nucleotide sequence alignment. Sequence lengths are constrained only by available memory; the product of sequence lengths in the current implementation can be up to 2(22). The machine is implemented as two NuBus boards connected to a Mac IIf/x, using a mixture of TTL and FPGA technology clocked at 10 MHz. The boards are completely functional, and yield a 15-fold performance improvement over an unassisted host. PMID- 8481829 TI - Euthanasia: honoring a life. PMID- 8481830 TI - Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment. AB - We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150-450 micrograms/day for 6-33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2 +/- 4.2 micrograms/liter versus 8.0 +/- 3.3 micrograms/liter, P < 0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r = 0.67, P < 0.001). Also IGF-I concentrations were positively correlated with BGP (r = 0.66, P < 0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146 +/- 46 micrograms/liter versus 127 +/- 44 micrograms/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation. PMID- 8481831 TI - Impact near the hip dominates fracture risk in elderly nursing home residents who fall. AB - Hip fractures among the elderly are a significant and rapidly growing public health problem. The prevailing view is that most hip fractures are the consequence of age-related bone loss or osteoporosis. However, because over 90% of hip fractures are the result of falls, we have undertaken a falls surveillance study to determine if factors related to the mechanics of falling are associated with increased risk of hip fracture. Case subjects with hip fracture and control subjects without hip fracture were sampled from falls recorded at the Hebrew Rehabilitation Center for Aged, a chronic care facility. Fall information was obtained by interview of the subject and witnesses if the fall was witnessed. Data were analyzed by multiple logistic regression. Increased risk of hip fracture from a fall was associated with impacting on the hip or side of the leg and potential energy associated with the fall. Quetelet, or body mass index, was inversely related to fracture risk. The adjusted odds ratio of hip fracture for a fall involving impact on the hip region was 21.7 (95% confidence interval, 8.2 58). The potential energy associated with these falls was an order of magnitude greater than the average energy required to fracture elderly, cadaveric, proximal femurs in earlier in vitro experiments. We conclude, therefore, that a fall from standing height should no longer be considered minimal trauma but rather trauma of sufficient magnitude to pose a high risk of hip fracture if impact occurs on the hip and if energy-absorbing processes are inadequate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481832 TI - Geometric variables from DXA of the radius predict forearm fracture load in vitro. AB - The purpose of this investigation was to determine the cross-sectional geometry of the radius in female and male cadaveric specimens using dual-energy X-ray absorptiometry (DXA), to measure the accuracy of this technique compared with a digitizing procedure, and to measure the correlation between these DXA-based geometric variables and the load required to produce a forearm fracture. Paired intact forearms were scanned at a distal site and at a site approximately 30% of the forearm length from the distal end. The cross-sectional area and the moments of inertia of two sections at 10 and 30% of the forearm length were computed from the X-ray attenuation data. One member of each pair was then sectioned at the 30% location, which is mostly cortical bone, and the section was traced on a digitizing pad. The other forearm was loaded to failure in a servohydraulic materials test system. The DXA-based area and moment of inertia at 30% correlated significantly with the digitized results (r2 = 0.93 for area; r2 = 0.95 for moment; P < 0.001). The conventional bone mineral density from DXA did not associate significantly with failure load, but the minimum moment of inertia and the cross-sectional area at 10% correlated in a strong and significant manner with the forearm fracture force (r2 = 0.67 for area; r2 = 0.66 for moment; P < 0.001). The determination of radial bone cross-sectional geometry, therefore, should have better discriminatory capabilities than bone mineral density in studies of bone fragility and fracture risk. PMID- 8481833 TI - Plasma levels of parathyroid hormone, vitamin D, calcitonin, and calcium in association with endurance exercise. AB - Nine male marathon runners were investigated during habitual training (week 0), after 3 weeks of training break (week 3), and after 2 weeks (week 5) and 4 weeks (week 7) of retraining. Maximal oxygen uptake, body fat (BF), and plasma levels of 25(OH)D3, 1,25(OH)2D3, parathyroid hormone (PTH), calcitonin (CT), albumin, and albumin-corrected calcium were determined throughout weeks 0-7. The maximal oxygen uptake decreased after training break and increased during retraining (P = 0.002). BF did not change significantly. Plasma 1,25(OH)2D3 was elevated after training break and decreased after 2 and 4 weeks of retraining [week 0: 44.0 +/- 3.7 (SEM) pg x 1(-1); week 3: 52.4 +/- 6.0 pg x 1(-1); week 5: 42.0 +/- 2.8 pg x 1(-1); week 7: 36.9 +/- 2.3 pg x 1(-1); P = 0.03]. Plasma 25(OH)D3 did not change significantly. Plasma PTH increased throughout the training break and retraining (week 0: 1.36 +/- 0.25 pmol x 1(-1); week 3: 2.02 +/- 0.43 pmol x 1(-1); week 5: 2.23 +/- 0.60 pmol x 1(-1); week 7: 2.63 +/- 0.34 pmol x 1(-1); P = 0.03). Albumin-corrected calcium values were transiently decreased during retraining (week 3: 2.77 +/- 0.08 mM; week 5: 2.47 +/- 0.05 mM; week 7: 2.66 +/- 0.07 mM; P = 0.01). Plasma CT did not change during training break, but was transiently decreased during retraining (week 0: 9.97 +/- 0.39 pmol x 1(-1); week 3: 9.91 +/- 0.37 pmol x 1(-1); week 5: 8.19 +/- 0.50 pmol x 1(-1); week 7: 9.02 +/- 0.45 pmol x 1(-1); P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481834 TI - Marathon running accompanied by transient decreases in urinary calcium and serum osteocalcin levels. AB - We evaluated the effects of marathon running on bone metabolism in 23 noncompetitive athletes (15 women, 8 men, age range 23-55 years). The volunteers were studied 10 days before, immediately after, and 1, 3, and 5 days after the run. Serum osteocalcin levels were decreased on average by 20% (from 4.9 to 3.9 micrograms/liter, P = 0.005) in men and by 10% (from 4.9 to 4.4 micrograms/liter, P < 0.05) in women at the end of the marathon, with lowest osteocalcin levels (67 55% of the prerun levels) encountered 1 day after the marathon. The activity of bone alkaline phosphatase was decreased in women (from 66.3 to 62.3 U/liter, P < 0.05) after the run, and this drop was detectable at each checkup after the run. Urinary excretion of calcium was lowered on average by 82% in men (from 2.8 to 0.5 mumol/minute, P < 0.05) and by 76% in women (from 2.5 to 0.6 mumol/minute, P < 0.005) after the run, but had already returned to prerun levels 1 day after the marathon. Urinary excretion of hydroxyproline tended to rise in both men and women, but the change did not reach statistical significance in either sex. These changes suggest a transient suppression in osteoblast function during the marathon. PMID- 8481835 TI - Bone mineral density in weight lifters. AB - The effect of intense physical training on the bone mineral content (BMC) and soft tissue composition, and the development of these values after cessation of the active career, was studied in 40 nationally or internationally ranked male weight lifters. Nineteen were active and 21 had retired from competition sports. Fifty-two age- and sex-matched nonweight lifters served as controls. The bone mineral density (BMD) in total body, spine, hip, and proximal tibial metaphysis was measured with a Lunar Dual-energy X-ray absorptiometry (DXA) apparatus and the BMD of the distal forearm was measured with single photon absorptiometry (SPA). Seventeen of the lifters had been measured earlier with SPA in the forearm and 23 in the tibial condyle during their active career in 1975. The BMD was significantly higher in the weight lifters compared with the controls (10% in the total body P < 0.001, 12% in the trochanteric region P < 0.001, and 13% in the lumbar spine P < 0.001). All measured regions except the head showed significant higher bone mass in the weight lifters compared with the controls. In older lifters, the difference from the controls seemed to increase in total body and lumbar vertebrae (BMD), but remained unchanged in the hip. Significant correlation was found between the SPA measurements in 1975 and the corresponding measurements 15 years later in both the forearm (r = 0.51, P < 0.05 at the 1-cm level and r = 0.87, P < 0.001 at the 6-cm level) and in the tibial condyle (r = 0.61, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481836 TI - Growth hormone involvement in the regulation of tartrate-resistant acid phosphatase-positive cells that are active in cartilage and bone resorption. AB - Young male Sprague-Dawley rats (5-7 weeks old, 80-120 g) were hypophysectomized (HX) and maintained on thyroxin and dexamethasone replacement therapies. Ten days after surgery, some HX rats received a single injection of human growth hormone (hGH), and others five daily injections of hGH. Tartrate-resistant acid phosphatase (TRAP) histochemistry was employed in order to evaluate the number of cells of resorptive potential in the metaphyseal bone of the proximal tibiae of HX rats and was compared with normal rats and HX rats that further received hGH replacement therapy. In normal rats, two populations of TRAP-positive cells were identified: multinuclear cells, which showed histological characteristics of osteoclasts, and small mononuclear cells, the number of which was overwhelming when compared with the number of TRAP-positive multinuclear cells. Both populations were reduced in the HX rat, but more so the mononuclear cells, which were assumed to represent the precursor pool of mature osteoclasts and chondroclasts (P < 0.005). Five daily injections of hGH to HX rats brought about a significant increase in the number of TRAP-positive multinuclear cells, the number of nuclei of these cells, and the number of mononuclear TRAP-positive cells, throughout the metaphyseal bone (P < 0.05). A single injection of hGH increased only the number of TRAP-positive multinuclear cells in the trabecula/bone marrow interface (P < 0.05), indicating a very rapid fusion of precursor cells into mature osteoclasts in that particular location.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481837 TI - Proliferative responses to estradiol, IL-1 alpha and TGF beta by cells expressing alkaline phosphatase in human osteoblast-like cell cultures. AB - The use of primary (nontransformed) bone cell cultures is hampered by their cellular heterogeneity. Primary cultures of osteoblast-like cells have been shown to proliferate in response to several osteotropic agents, but because mixed cell populations are present it is uncertain whether a true osteoblastic response was observed. By combining (1) localization of [3H]-thymidine incorporation into the nuclei of actively dividing cells by autoradiography with (2) subsequent induction of osteoblast differentiation by 1,25(OH)2D3 to optimize the number of cells expressing high alkaline phosphatase activity and (3) its localization by histochemical staining, it is possible to measure the proliferation of cells that are capable of expressing a more mature osteoblastic phenotype in heterogeneous human trabecular bone cell cultures. Over a 72-hour incubation period, rhIL-1 alpha (0.2-2 ng/ml) exerted a dose-dependent stimulation of proliferation of cells expressing alkaline phosphatase. Purified human TGF beta 1 produced a biphasic increase in the proliferation of these cells (0.01-1 ng/ml) but 17 beta and 17 alpha-estradiol (10(-12)-10(-8) M) failed to consistently regulate cell growth. Furthermore, 17 beta-estradiol did not reproducibly modulate proliferation induced by IL-1 alpha or TGF beta when added together in cultures. This procedure represents a more accurate method for the assessment of osteoblast proliferation in primary bone cell cultures and demonstrates that estrogen is not mitogenic for human osteoblasts and does not potentiate the actions of putative local stimulators of osteoblast replication. PMID- 8481838 TI - Effect of treadmill exercise on vertebral and tibial bone mineral content and bone mineral density in the aged adult rat: determined by dual energy X-ray absorptiometry. AB - Dual energy X-ray absorptiometry (DXA; Hologic QDR-1000W) in an ultrahigh resolution mode, was used to examine the changes in tibial/fibula and vertebral L4 + L5 bone mineral content (BMC) and bone mineral density (BMD) in each 14 month-old female rat at 0, 9, and 16 weeks of study. Twenty rats were randomized by a stratified weight method into two groups, control and exercised. Exercise consisted of running on a flat-bed treadmill, 17 m/minute, 1 hour/day and 5 days/week. As compared with the control group, a significant increase in tibia/fibula BMC and vertebral BMD was apparent at 9 weeks after exercise training (P = 0.014 by 2-way analysis of variance). The slope of the gain of the tibia/fibula BMC and BMD by 16 weeks of training was ninefold and fivefold higher than that of the control group (P < 0.01 and P < 0.05, respectively, by Mann Whitney test). The correlation coefficient (r) between the final dry weight of excised bone and the final BMC of the intact rat was 0.843 and 0.71 for tibia/fibula and vertebrae, respectively. In summary, we found that in the aged rat, by 9 weeks, exercise increases BMC and BMD in the tibia, whereas in the vertebrae, only increases in the BMD were found. This study demonstrates that this precise and accurate DXA technique is useful in a longitudinal study of in vivo bone mineral changes in the rat over time by taking into account the individual variation between animals as well as changes between groups. PMID- 8481839 TI - Effects of two non-endurance exercise protocols on established bone loss in ovariectomized adult rats. AB - The effects of non-endurance exercise on bone properties were evaluated in 9 month-old sham-operated (SH) and ovariectomized (OVX) rats. The studies were started 3 months postsurgery, after bone mass was decreased in OVX rats. The sham and OVX rats were either kept sedentary (SED) or were trained to run with one of two protocols: 12 m/minute, 50 minutes/day, 4 days/week (low intensity, frequent, EX-1); or 21 m/minute, 40 minutes/day, 1 day/week (moderate intensity, infrequent, EX-2). A group of seven rats evaluated at the beginning of the study served as baseline control. The bone mineral was assessed by the ash weight of the left femur, tibia, and 4th lumbar vertebra. Biomechanical (strength, deformation, stress, strain, and stiffness) and morphometric (length, cortical and medullary area, moment of inertia) properties were evaluated for the right femur. There was a significantly lower bone mineral and mechanical properties in OVX-SED (n = 7) than in SH-SED (n = 10) rats. The OVX-EX-1 (n = 6) rats had higher ash content of femur and tibia than OVX-SED rats, but the change was significant only for tibia. The EX-2 had no effect on the ash content, but femur stress was higher in OVX-EX-2 (n = 8) than in OVX-SED rats. The femur yield force and deformation were improved in OVX rats with both exercise protocols, whereas the vertebra ash weight, femur strain, modulus of elasticity, length, cortical area, and moment of inertia were not changed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481840 TI - Material damping for monitoring of density and strength of bones. AB - The aim of this work was a preliminary assessment of the feasibility of using in vivo measurements of mechanical properties of bones to detect mineral loss and further to relate them to the tendency of the bone to fracture in the case of loss of minerals, such as in osteoporosis. Previous studies of bone strength in vitro have demonstrated that the decrease in bone strength in both the spine and the femur has strong correlation with the mineral content (BMC) measured with bone densitometry. It was demonstrated that loss of mineral in the bone is accompanied by substantial change of the main mechanical properties, decrease of the Young's modulus, and increase of the damping factor. The change in those properties is one order of magnitude greater than the change in bone density. Moreover, increase of bone density, by way of training, resulted in decrease of the damping factor that also was substantially greater than the change in density. The tests showed clearly that the change in mechanical properties was much greater than the change in bone mass density. This offers an attractive new alternative to the detection of bone mass loss as it appears that the change of the bone mass is well correlated to the change in these mechanical properties. In particular, the change in the damping factor of the material was found to be much more substantial than the bone density change. Therefore, the damping mechanism offers the vehicle for a direct assessment of the bone tendency to fracture due to the loss of mass, as tendency to fracture and mass loss are known to be related.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481841 TI - Aminoalkylbisphosphonates, potent inhibitors of bone resorption, induce a prolonged stimulation of histamine synthesis and increase macrophages, granulocytes, and osteoclasts in vivo. AB - Aminoalkyl derivatives of bisphosphonates are potent inhibitors of bone resorption. A single I.P. injection of 4-amino-1-hydroxybutylidene-1,1-bis phosphonate (AHBuBP) induced a prolonged enhancement of histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung, and liver of mice and resulted in an increase in histamine. The induction of HDC by the agent was dose dependent (16-80 mumol/kg) and peaked 3-4 days after its injection (40 mumol/kg). Repeated S.C. injections of smaller doses of AHBuBP (0.32 or 1.6 mumol/kg/day) for 4 days also enhanced HDC activity. However, the minimum dose capable of inhibiting bone resorption (0.064 mumol/kg/day) was lower than that inducing HDC. Unexpectedly, AHBuBP, at the doses inducing HDC, increased macrophages, granulocytes, and even osteoclasts. The size of osteoclasts was also enlarged by the agent. Another aminobisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, but none of non-amino derivatives, also exhibited essentially the same effects as those of AHBuBP. These results indicate that in spite of increase in osteoclasts and their enlargement, bone resorption is still inhibited by amino bisphosphonates. As granulocyte and granulocyte-macrophage colony-stimulating factors and interleukin 3 induce HDC in hematopoietic organs, and histamine has a hematopoietic activity, the HDC induction by aminobisphosphonates may be relevant to the proliferation of progenitor cells of macrophages, granulocytes, and osteoclasts. PMID- 8481842 TI - Effect of 24R,25-dihydroxyvitamin D3 on the formation and function of osteoclastic cells. AB - Previous reports demonstrated that the administration of large doses of 24R,25 dihydroxyvitamin D3 [24R,25(OH)2D3] to animals with normal vitamin D supply causes an increase in bone volume with reduced bone resorption and decreased osteoclast number. The present study was undertaken to clarify if 24R,25(OH)2D3 has any inhibitor effect on the formation and function of osteoclasts. The effect of 24R,25(OH)2D3 on the formation of osteoclastic cells was examined by measuring the number of tartrate-resistant acid phosphatase-positive multinucleated cells (MNCs) formed from hemopoietic progenitor cells obtained from spleens of 5 fluorouracil-treated mice. Treatment with 1,25(OH)2D3 or parathyroid hormone fragment 1-34 [PTH(1-34)] stimulated osteoclast-like MNC formation in a dose dependent manner. Addition of 24R,25(OH)2D3 alone showed a weak stimulatory effect on MNC formation at 10(-6) M, which appeared to be due to its binding to 1,25(OH)2D3 receptors. In contrast, when 24R,25(OH)2D3 was added together with 1,25(OH)2D3 or PTH(1-34), it inhibited osteoclast-like MNC formation stimulated by these hormones. A significant inhibition of MNC formation was observed with 10(-7) M 24R,25(OH)2D3, and the stimulatory effect of 1,25(OH)2D3 or PTH(1-34) was almost completely eliminated with 10(-6) M 24R,25(OH)2D3. Neither 24S,25(OH)2D3 nor 25(OH)D3 exhibited a similar inhibitory effect. The effect of 24R,25(OH)2D3 on the resorptive function of osteoclasts was examined by measuring the formation of resorption pits by mouse bone cells on dentine slices. Treatment with 24R,25(OH)2D3 also inhibited the resorption pit formation stimulated by 1,25(OH)2D3 or PTH(1-34) with similar dose response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481843 TI - Detection of renal allograft dysfunction with color Doppler flow ultrasound. AB - Thirty-six color Doppler flow (CDF) ultrasound studies were performed on 28 allograft kidneys to assess the capability of this technique in diagnosing transplant dysfunction through morphology and Doppler spectra. The composite score obtained from ultrasound images showed no statistical significance. Quantitative studies with Pulsatility Index (PI) and Resistive Index (RI) after localization of the arcuate, interlobar, segmental and main renal arteries by CDF revealed significant differences between normal functioning graft kidneys and the group of acute rejection, as well as the group of acute tubular necrosis (ATN) (P < 0.05). No apparent change was demonstrated in patients with chronic rejection. When PI was greater than 1.60 or RI was greater than 0.80, the transplant kidney was more likely to be rejected, though possibility of ATN should be considered. RI was easier to calculate, and correlated better than PI with the serum creatinine level. CDF expedited the Doppler spectrum study. PMID- 8481844 TI - Acute acalculous cholecystitis. AB - To demonstrate the importance of early detection and diagnosis of acute acalculous cholecystitis, 34 patients with this disease, were studied retrospectively. Twenty patients had a delay between the onset of symptoms and operative intervention, exceeding 48 hours; five of them were found to have a perforated gallbladder during operation; however, no such complication was encountered in the 14 patients who underwent surgical treatment within 48 hours of onset. Sixteen patients had post-operative complications, and four patients who died produced in a mortality rate 11% (4/34). Three mortality cases had coexisting cardiovascular disease and the operation was also delayed for more than 48 hours. PMID- 8481845 TI - Bacteriology of necrotizing fasciitis: a review of 58 cases. AB - Necrotizing fasciitis is a relatively rare soft tissue infection that is characterized by rapidly widespread necrosis of the fascia and subcutaneous tissue. Fifty-eight cases were reviewed over a 5.5-year period. The majority of wound cultures were polymicrobial and single culture rate was 18.6%. The facultative organisms were most frequently recovered. The most frequently discovered bacteria were E. coli, Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus aureus and group D enterococcus. The overall mortality rate was 48.3%. Early recognition, serial radical surgical debridement and strong and appropriate antibiotics were essential for survival. PMID- 8481846 TI - [Ventilation tube insertion for treating adult otitis media with effusion]. AB - The etiologic factors and treatment of otitis media with effusion (OME) in children are well described and established. On the contrary, little has been published with regard to OME in adults and its treatment. To further investigate this problem, we reviewed the records of all adult patients who had received ventilation tube (VT) insertion for OME in VGH-Taipei from 1983 to 1986. There were 335 VT insertions performed on 140 adult patients whose follow-up periods were longer than 6 months. Among them, fifty patients received more than one VT insertion due to recurrence of OME in one or both ears. The average follow-up period was more than 4 years. The coexistence of nasal diseases was found in 46% of the adult OME patients. The mean extrusion time of the VT was 10.2 months. After VT insertions, the improvements of mean air conduction and mean air-bone conduction gap were 10.1 and 11.8 dB respectively. After the extrusion or removal of VT, there was no recurrence of OME in 50 ears (14.9%). Recurrence of OME occurred in 199 ears (59.4%). Dry persistent perforations of the eardrums were found in 27 ears (8.1%). Discharging persistent perforations were noted in 24 ears (7.2%). No recurrence of OME was observed in 24.2% of the ears with serous effusion fluids, whereas only 4.8% of the ears with mucoid fluids were free from recurrence during the follow-up period. Post-intubation otorrhea, which was the most common complication, developed in 92 ears (27.5%). Our results suggest that the recurrence rate of OME after extrusion of VT is high in the adult patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481847 TI - [Analysis of malignancy of human brain glioma with silver colloid-staining technique]. AB - The nucleolar organizer regions are loops of DNA that exist in cellular nucleolus and possess ribosomal ribonucleic acid genes. Ribonucleic acid polymerase I acts on these areas. This experience collects 52 primary human gliomas at TSGH from 1984 to 1989. These included 23 astrocytomas, 8 anaplastic astrocytomas and 21 glioblastoma multiforms. After thin cutting on slides and deparaffinizing, we stained each by the silver colloid technique. We counted the total quantity of Ag NOR dots of over 400 tumor cells of each case and average of Ag-NOR dots per cell (+/- standard error of the mean) with X1000 oil lens. The results are 1.68 +/- 0.05, 2.00 +/- 0.10; 2.55 +/- 0.13 respectively, showing significant differences among these. The average Ag-NOR paralleled the degree of histopathological malignancy. With the average Ag-NOR of tumor cells to predict the patients prognosis, we found that the group containing patients with less than 2.00 Ag-NOR per cell had better prognosis than the group with 2.00 Ag-NOR or more. The silver colloid-staining technique is a simple, rapid and reproducible method to evaluate the malignancy of human brain gliomas and to estimate the long-term prognosis of patients. PMID- 8481848 TI - [Psychogenic dizziness]. AB - Psychogenic dizziness is defined as recurring or persistent symptoms of balance dysfunction, inconsistent with organic vestibular disease as determined by history, clinical examination and pertinent investigations, and consistent with emotional origin. Of 1,335 patients seen in our dizziness clinic between January 1988 and August 1991, psychogenic dizziness was diagnosed in 180 (13.5%) patients. There were 67 men and 113 women aged from 12 to 77 years (mean age 40.2 years). The characteristics of psychogenic dizziness are: (1) continuous dizziness for long periods of time; (2) younger patients; (3) predominant female; (4) associated symptoms of panic attack, such as headache, breathlessness, nausea, sleep disturbance, paresthesias, anxiety and palpitation; (5) symptoms of aggravation due to stressful life events; (6) normal neurotological bedside examination; (7) hyperventilation reproduced accurately. The electronystagmographic results of 74 patients show normal bithermal caloric responses in 47 patients (63.5%), caloric hyperactivity in 21 patients (28.4%), canal paresis in four patients (5.4%), canal paresis with directional preponderance in two patients (2.7%), large random voluntary eye swings or severe blinking in 35 patients (47.3%), and spontaneous nystagmus (slow phase velocity < 6.5 degrees/s) in four patients (5.4%). There were 31 patients who consulted psychiatrists with diagnoses of anxiety (51.6%), depression (16.1%), insomnia (12.9%), psychosomatic disorder and adjustment disorder. Treatment of patients with psychogenic dizziness must be directed at the underlying anxiety. Psychiatric consultation is necessary. PMID- 8481849 TI - [A responses to Ko's mental health questionnaire by patients with peptic ulcer disease]. AB - The author conducted a study of personality characteristics using Ko's mental health questionnaire (KMHQ) on 279 patients who received upper gastrointestinal endoscopic examination at the Taichung Veterans General Hospital during the three months from May 12 to August 11, 1983. Those patients, 203 men and 76 women, voluntarily entered the study. Forty-four patients were randomly selected to receive the same KMHQ again 18-21 months later. The 13 subscales of the KMHQ were confirmed to have a good value of the test-retest reliability (r = 0.419 to 0.796, p < 0.001). Based on the findings of endoscopic examination, 279 patients were divided into two groups: the experimental group of 104 patients (those with gastric ulcer, duodenal ulcer and mixed abnormal findings) and the control group of 175 patients (those with normal findings, superficial gastritis and duodenitis). A comparison of the 13 subscales of the KMHQ between these two groups of patients revealed no significant differences in the mean scores except that a greater obsessionality index (scale VII) was seen in the experimental group than in the control group (t = 2.35, p < 0.05). In conclusion, peptic ulcer patients with positive endoscopic findings have the characteristic of significant greater obsessionality according to KMHQ. PMID- 8481850 TI - One-stage operation for bilateral spontaneous pneumothorax using imaged thoracoscopic technique: case report. AB - Bilateral apical bullae have previously been approached by staged or one-staged bilateral thoracotomy. In a 26-year-old male with bilateral primary spontaneous pneumothorax, bilateral apical bullae were successfully removed with thorough pleural abrasion using imaged thoracoscopic surgery in one operation. Postoperative pain was markedly reduced, pulmonary toilet was easily accomplished and cosmetic appearance of the scar satisfactory. Bilateral bullectomy and pleurodesis using imaged thoracoscopic surgery can, therefore, provide a simpler and safer option for bilateral pneumothorax. PMID- 8481851 TI - Triplet pregnancy in premature ovarian failure after oocyte donation and in vitro fertilization: a case report and review of literature. AB - Oocyte donation in premature ovarian failure patients has become an extended indication for In Vitro Fertilization (IVF) procedure. Here the first case report is presented in Taiwan, R.O.C. of a triplet pregnancy in a patient with premature ovarian failure. After an adequate hormonal replacement therapy with oral premarin and intramuscular progesterone for endometrium preparation, the transfer on D15 of four embryos (with donated oocytes and IVF) resulted in implantation of three. Pregnancy support was provided also by oral premarin and intramuscular progesterone until the tenth week of gestational age (GA). The patient received Caesarean section at 35 weeks GA with delivery of three healthy babies weighing 2530 gm, 2420 gm, and 1810 gm respectively on Aug. 17, 1990. PMID- 8481852 TI - [Twin pregnancy complicated by single intrauterine death. Report of six cases and literature review]. AB - From 1982 to 1991, six twin pregnancies, in which one of the fetuses died in utero, have been encountered. The causes of antepartum death in twin gestation could be identified in four cases; one with abruptio placenta, one with twin-to twin transfusion syndrome, one with twisting of cord and one with velamentous insertion of cord. All six surviving infants had no abnormality in the follow-up of two to seven years. Although a conclusion about the prognosis could not be drawn from such a small series, these good results may have resulted from 1) 2 cases having been dichorionic twins, and 2) the other 4 monochorionic twins of 31 36 gestation weeks were delivered 1 to 5 days after the diagnosis. Conservative treatment was usually suggested until the fetal lung was mature enough for induction of labor. One case was treated after the death of its counterpart with tocolytic agent for a further 15 days because of prematurity. Cesarean section was performed finally for fetal distress resulting from chronic abruption placenta. The other five cases were delivered through vaginal route. According to experience as well as literature review, to improve the prognosis, obstetricians should be familiar with the management of one fetal death in twin pregnancy, especially in those with monchorionic twins. PMID- 8481853 TI - [Cantrell's pentalogy: a case report]. AB - Cantrell's pentalogy is a congenital anomaly resulting from embryologic development defect. The anomalies observed in this disorder were: (1) a midline, supraumbilical abdominal wall defect, (2) a defect of the lower sternum, (3) a deficiency of the anterior diaphragm, (4) a defect in the diaphragmatic pericardium, (5) congenital intracardiac defects. Its occurrence in the newborn is quite uncommon, though it was first described by Cantrell and his colleagues in 1958. A one-day-old male fullterm newborn was presented. Omphalocele and partial ectopia cordis were noted immediately after birth. Echocardiogram revealed tetralogy of Fallot with atrium septal defect. Operative findings were sternal cleft, pericardial defect and ventral diaphragmatic defect. The literature on clinical manifestations, embryogenic defect and management of Cantrell's pentalogy is reviewed briefly. PMID- 8481854 TI - [Maturation of ganglioneuroblastoma to ganglioneuroma: a case report]. AB - A 1 year and 7 months old girl had suffered from chronic diarrhea for 6 weeks. A huge abdominal mass was found. She received subtotal resection of the tumor and the histological picture showed ganglioneuroblastoma. Then, 12 courses of chemotherapy (including cyclophosphamide, doxorubicin cisplatin and etoposide) were given for 8 months, but the residual tumor mass over the previous surgical area was still noted by CT scan. A second excision of the tumor was performed and histology showed a picture of ganglioneuroma incidentally. Chemotherapy was discontinued. The patient is still alive and well for more than one year. PMID- 8481855 TI - [Acute amphetamine intoxication with catatonia: a case report]. AB - A marked increase of cases of amphetamine intoxication has been witnessed in Taiwan over the past two years, and poisoning accounts for the direct cause of death in some cases of them. We report a case of 30-year-old woman, who developed immobility, rigidity, mutism and staring after the intake of four grams of amphetamine powder. She initially had generalized twitching, but finally came to a state of total immobility. One hour after admission, apnea and cyanosis occurred suddenly and she died about half an hour later. Chronic amphetamine intoxication with catatonia has been reported in Japan, but acute amphetamine intoxication with catatonia has never been reported in the literature. In this report, we explore the possible mechanisms of catatonia in amphetamine intoxication and its clinical significance. Catatonia is supposed to be one of the poor prognostic signs of acute amphetamine intoxication that requires intensive care. PMID- 8481856 TI - The advocacy role of the perioperative nurse. PMID- 8481857 TI - Endoscopic surgery--scope vs scapel. PMID- 8481858 TI - The joys of initiating laparoscopic surgery in a small rural hospital. PMID- 8481860 TI - AIDS and health promotion. PMID- 8481859 TI - Perioperative care of the neonate. AB - The neonate is a unique individual with his/her own needs. This article deals with the adjustments the neonate has to make to extrauterine life; some of the differences between neonates and older children and adults, and the special needs of the neonate who needs surgery. PMID- 8481861 TI - AIDS and human sexuality. AB - The sexual behaviours placing an individual at risk for HIV infection are those also placing him/her at risk for gonorrhoea, syphilis, hepatitis B, chlamydia and unplanned pregnancy. This article proposes that approaches to HIV prevention must be included within a broad context of human sexuality. To address disease prevention in the absence of including people's relationships, social, behavioural and emotional needs is futile. Compartmentalization, denial of risk by various populations, and societal barriers are all factors to be overcome in the fight against HIV transmission. Specific strategies involved in a comprehensive approach are outlined under the categories of predisposing, enabling and reinforcing factors contributing to healthy sexual behaviour. PMID- 8481862 TI - HIV/AIDS education participation by the African community. AB - Africans United to Control AIDS, an HIV/AIDS community-based programme, is described. The project goal is to increase HIV/AIDS awareness among the African community in Metropolitan Toronto within a culturally appropriate context. A brief overview of African immigration to Canada is presented. Community participation, programme activities, outreach strategies and education sessions are discussed. Outreach strategies include the development of education materials and media contacts. The section on education sessions includes the preparation, delivery and evaluation of these sessions, and subjects such as misconceptions, marriage, sexuality, confidentiality, basic HIV/AIDS information, condoms, homophobia, use of videos. Success, failures, barriers to HIV/AIDS education and overcoming these barriers are discussed throughout this article. PMID- 8481863 TI - Grade 6 students benefit from Learning About AIDS. AB - The purpose of this study was to assess the impact of an educational program, Learning About AIDS, on Grade 6 students' knowledge of HIV/AIDS and attitudes towards persons living with AIDS(PLWAs). A pretest/post-test/follow-up comparison group design was utilized to evaluate this intervention. Findings indicated that Grade 6 students who received Learning About AIDS were significantly more knowledgeable about HIV/AIDS at post-test and follow-up than were comparison group students. As well, the treatment group students' attitudes toward PLWAs were significantly more positive than those of the comparison group at both post test and follow-up. It was concluded that Learning About AIDS was a beneficial and worthwhile program for these Grade 6 students. PMID- 8481864 TI - [Women, AIDS and sexually transmitted diseases: strategies of action for prevention and education]. AB - AIDS and STDs are major health problems among Canadian women. The prevention of HIV and STD transmission will possibly be more effective if certain factors pertaining to social status and affecting behaviour patterns are understood and taken into account. The Ottawa Charter can be used as a reference in designing prevention and education programs. PMID- 8481865 TI - AIDS education from a front line worker's perspective. PMID- 8481866 TI - The epidemiology of HIV and AIDS in Canada: current perspectives and future needs. AB - There is little doubt the HIV epidemic is of enormous public health importance for Canadians. Currently, it is estimated that between one and two in 1,000 adult Canadians are infected with HIV. Compared to other industrialized countries, Canada is a country of intermediate incidence. Much effort has gone into developing and maintaining the AIDS surveillance system as well as carrying out HIV seroprevalence studies in selected populations. In spite of under-reporting of AIDS cases (estimated to be 12-25%), the available data provide a general picture of the HIV epidemic in Canada. Nevertheless, a number of questions remain unanswered, and we need more information to plan preventive interventions and provide services to persons who are already infected. In this article, we present a brief overview of the epidemiology of AIDS and HIV in Canada. We identify some disturbing trends in the epidemic and reiterate the need for more information to improve our preventive efforts and help set research priorities to help plan future studies. PMID- 8481867 TI - AIDS prevention programs in a smaller community. AB - This paper discusses the development and implementation of an AIDS prevention program in a non-urban area. A non-urban area provides challenges, issues and barriers not found in a large urban area. Characteristics of smaller centre residents, their attitudes and values will shape their response to HIV/AIDS issues. To facilitate HIV service delivery and program implementation, a variety of strategies to facilitate "ownership" are required to create a supportive, caring environment for families affected or infected by AIDS within small community settings. PMID- 8481868 TI - [Quebec after a decade of epidemic HIV infection: what is the status of interventions in health promotion?]. AB - Quebec has the highest rate in Canada of AIDS among injection drug users (IDU), women and individuals originating from Model II countries. Long-term prevention of HIV transmission in Quebec calls for intervention measures (individual risk reduction) as well as the implementation of health promotion strategies. A rigorous conceptual framework like the Ottawa Charter for Health Promotion allows us to better identify relevant measures to be developed in order to curb the HIV epidemic in the province of Quebec. PMID- 8481869 TI - AIDS and the aboriginal community. AB - A concise portrait of HIV and AIDS within the Aboriginal community is difficult to present. Just as there are different customs and traditions among tribes, so are there different ways by which this issue is being addressed. The response to HIV/AIDS in the Aboriginal community is the process of moving from an individual or personal perspective to an immediate and extended family approach through the community, nation or society, and finally to the greater picture, Mother Earth. We don't necessarily move through in this order, rather we go back and forth as the need arises. When we deal with HIV or AIDS, it is important to view how this will affect our whole life: physical, mental, emotional and spiritual aspects of ourselves as well as financial, psychosocial and other dimensions. The teachings and study of children, youth, adults and elders are also discussed. We recognize the work we do in this area now will be a tool for survival in the future. PMID- 8481870 TI - HIV/AIDS implications for the social service sector. AB - This paper examines the response of the social service sector to the HIV/AIDS crisis in Canada. Examples of innovative projects and programs are provided and the challenges of responding to needs in rural and remote settings and special populations are explored. The importance of forging effective partnerships between social service professionals and community-based agencies is highlighted and the need for the social service infrastructure to adapt to the highly variable needs of PLWAs is highlighted. PMID- 8481871 TI - Health promotion and AIDS prevention. PMID- 8481872 TI - Shooting off fireworks: the successes and failures of an intensive, broad-based AIDS awareness campaign. AB - Broad-based AIDS awareness campaigns often involve media advertisements, posters and/or pamphlets intended to address a specific concern related to HIV/AIDS. They focus on safer sex, prevention for young adults, women's issues in relation to HIV, etc. During the autumn of 1991 a group of Manitoba AIDS organizations came together to organize, promote and deliver an eight-week AIDS Awareness Campaign that would address a broad spectrum of HIV/AIDS-related issues. Instead of attempting to solidify one prevention message, this campaign attempted to satisfy a variety of organizational agendas. Although it achieved its goals and was a very visible, but short-lived exercise in AIDS awareness, this campaign proved to be taxing on local community-based resources. PMID- 8481873 TI - Making HIV prevention work in the north. AB - Meeting the challenges of diverse cultures, numerous languages and great distances, the Northwest Territories discovered innovative ways to promote AIDS prevention. This article discusses obstacles to HIV prevention and techniques used to overcome them commonly found in health services for the NWT. For example, techniques for improved service delivery include reliance on decentralized services provided by regional health boards and Community Health Representatives. Further, the challenges posed by language diversity and cultural taboos against speaking openly about sexual matters have been partially overcome through the conversion of materials and concepts into aboriginal languages which are culturally appropriate. The article specifically discusses two AIDS education campaigns in which these techniques were utilized: namely, Health is a Community Affair Campaign (or the Door-to-Door Project) and local initiatives which hosted presentations by an Aboriginal person living with AIDS. PMID- 8481874 TI - Strategic planning for AIDS prevention--city of Toronto's experience. AB - This paper chronicles the planning process for the City of Toronto Department of Public Health's HIV/AIDS Prevention Program for 1991/1992. The process benefited from extensive consultation and input from Department staff, community representatives and the local Board of Health. A discussion of various questions that arise when planning a multifaceted program as well as practical suggestions are offered. The paper is written in the form of a letter to an incoming program coordinator. PMID- 8481875 TI - A health department's response to AIDS. Condomania: a public education intervention. AB - Experience gleaned from no smoking campaigns, seatbelt safety crusades, dental hygiene programs and other health promotion efforts, have pointed to the usefulness of social marketing principles in formulating and implementing broad based behaviour change programs. Using social marketing as a tool of health promotion, the Vancouver Health Department, in cooperation with the Vancouver Women and AIDS Project and the Positive Women's Support Network, implemented a three-year plan for six one-month condom awareness campaigns. Two of these campaigns have been successfully completed; the third is in the planning stage. The purpose of these campaigns is to make condoms a more acceptable feature of everyday sexual activity with 19-30 year-olds; women in particular have been targeted because of the increasing incidence of HIV among this population. The program consists of six major components. They are: design and production of campaign materials; public promotion-advertising; focused community education; volunteer recruitment and training; media relations; and program evaluation. PMID- 8481876 TI - Causal evaluation of impact of support workshop for HIV+ men. AB - A program logic model was used to design and evaluate a support workshop for men infected with HIV. The model identified three proximal outcomes leading to the ultimate goal of motivating participants to initiate ongoing support relationships. Path analysis was used to evaluate the workshop. The findings indicated the most important motivator to initiating ongoing support was the awareness among participants of the need to talk about their HIV status and risk of transmission and their feeling capable to do so. The proximal outcomes which contributed to this impact were: recognition of their own needs from listening to testimonials by others, developing awareness and skills by engaging in role plays, and learning options for discussion by participating in a sexual issues group. The workshop findings demonstrated the benefits of developing a pre program logic model and using causal evaluation to understand factors determining impact. PMID- 8481877 TI - A framework for health promotion ... a framework for AIDS. AB - During the 1980s, many AIDS prevention programs and interventions were established. However, program planning was often done with little consideration of the theoretical models useful for implementing successful interventions. In order to refine our AIDS prevention work in the future, it is necessary to look at theoretical frameworks to ensure we are designing and implementing effective and efficient AIDS prevention programs. It is suggested in this article that the health promotion framework is uniquely suited to AIDS prevention work. Challenges involved in the application of this framework are considered. Specific health promotion strategies such as community development, mutual aid, public policy and strengthening community health services are examined. The author concludes that health promotion is an effective model to address a comprehensive, coordinated, ethical response to HIV/AIDS prevention in Canada. PMID- 8481878 TI - Vascular evaluation. AB - This article details a variety of tests to detect venous insufficiency in the lower extremities, including palpation, stress testing, thermometry, thermography, segmental systolic pressures, Doppler studies, and plethysmography. PMID- 8481879 TI - Common peripheral vascular diseases. AB - Among the most common causes of morbidity and mortality in elderly individuals are the manifestations of the various peripheral vascular diseases. Many chronic degenerative diseases, which begin in middle age, are associated with peripheral vascular disease. Heart disease, hypertension, hyperlipidemia and diabetes are all risk factors for peripheral vascular diseases and also common degenerative conditions in our society. Other risk factors, such as diet, smoking, stress, lack of exercise, and obesity, are also closely associated with peripheral vascular disease. Aging itself is also a risk factor. Appropriate treatment for disease processes such as diabetes and hypertension and control of other preventable risk factors have been shown to reduce the morbidity and mortality seen in peripheral vascular disorders. Our rapidly aging population requires increasing amounts of medical resources, placing an enormous burden on society because the aged population are generally more dependent upon government sponsored health care services. The podiatric practitioner is in a position as a primary care provider to influence the health practices of our aging population. The implementation of a health practice that stresses prevention and wellness as well as the appropriate management and a referral of patients with peripheral vascular disorders will limit the morbid results of peripheral vascular diseases. PMID- 8481880 TI - Pharmacologic considerations in the geriatric patient. AB - A physician has the primary responsibility of first causing no harm. Unfortunately, the myriad of pharmacologic agents available to the clinician at times may make this directive difficult. When the variable of age-related changes is introduced, the clinician's task may seem almost impossible. The most important aspect of gerontology is that there are no constants. Age-related changes are inconsistent. Although liver function may vary little among the general population, virtually every other system is affected by the aging process. Additional factors that complicate treatment of the geriatric patient are multiple organ diseases, the intervention of multiple practitioners, and nutritional variation. Multiple diseases require polypharmacy with its greater tendency for drug-drug interaction and iatrogenic disease exacerbation. Multiple clinician involvement frequently lacks appropriate communication between the various specialties. Aging is commonly associated with drastic changes in dietary habits. An older person living alone may tend to miss more meals than other groups. Meals that are consumed may be inadequate and lack proper balance, especially adequate amounts of protein. Mineral and vitamin depletion are additional problems, especially with patients on diuretics and chronic anti infective therapy. In this article an attempt has been made to stimulate thought and generate an awareness in the podiatric practitioner of the considerations necessary when contemplating drug therapy in the geriatric population. Long lists of specific agents and recommended dosages, which quickly become outdated as newer drugs are introduced into the clinical arena, were intentionally not presented in this article. The author hopes that this article will generate interest in conducting additional research in podiatric applications of drugs. PMID- 8481881 TI - Diabetes mellitus. AB - Diabetes mellitus occurs commonly in the older patient and is frequently undiagnosed. In many cases, the initial manifestations of diabetes mellitus are lower extremity complications with which this disease is known to be associated. Unfortunately, these complications are similar to other age-related degenerative processes; therefore, vigilance for the detection of undiagnosed diabetes mellitus is essential in the evaluation and treatment of lower extremity pathologic conditions. PMID- 8481882 TI - Infection and the older patient. AB - An increasing number of elderly patients are in and out of doctors' offices, hospitals, nursing homes, and so forth, under continual medical care. Numerous invasive procedures allow for casual transfer of infectious diseases by fellow patients as well as health care workers. Dramatic increases in infectious diseases such as foot infections, pneumonia, staphylococcal infections and, because of necessary invasive and blood transfusion procedures, AIDS can be expected in the future. The elderly patient is often a debilitated, compromised, immunodeficient host who is highly susceptible to any number of infections. With this in mind as the population grows older, clinicians must begin to apply Universal Precautions in their practices if they have not already done so, and not underestimate any disease or symptom in any patient, regardless of their age or their condition. PMID- 8481883 TI - Physical medicine and its relationship to patient management. AB - In this article, some general concerns for the use of modalities and procedures for the older person are given. Management of the geriatric patient requires knowledge, understanding, and patience; it requires a clinician and health care staff that care about older people. It requires a recognition of the dignity of age and the intrinsic worth of each individual as a human being. It requires hope and an ability to project a quality of life, regardless of the living condition. It requires kind words and a hands-on effort. It requires an appreciation of life and a high degree of ethical and moral concern. PMID- 8481884 TI - Podiatric services in long-term care facilities. AB - The 1981 White House Conference on Aging in its Recommendation Number 148 stated that "comprehensive foot care be provided for the elderly in a manner equal to care provided for other parts of the body." This key position speaks to the need and right of foot care for all. The inclusion of appropriate podiatric services in long-term care programs will often produce dramatic effects. Immobility can be replaced by activity. Quality of care translates into improved quality of life. Support and encouragement can be directed to independence and a strong sense of personal identify and worth. Isolation can be replaced by interaction. When the quality of life decreases due to disease, disability, or age, those precious aspects of dignity must be restored to a maximum level by caring staffs. Because ambulation is a catalyst for life, podiatric care can help regain some of the lost dignity by keeping the patient walking and moving about, so that he or she can accept and participate in the social activities provided by the facility. PMID- 8481885 TI - Gerontology-geriatrics education. AB - This article provides a conceptual outline for the geriatric component of primary podiatric medicine as well as a summary of gerontologic considerations applicable to professional, postdoctoral, and continuing education. This article also focuses on health promotion and prevention. Given the projected number of older patients in the United States and the prevalence of foot problems needing care in the older population, the podiatrist of today and tomorrow must become and remain a viable member of the primary geriatric care team. PMID- 8481886 TI - Medicare. An administrative viewpoint. AB - Medicare was the first significant legislation that provided a health insurance program for a segment of our nation's population, initially for the elderly population and then expanded to include other chronically ill patients that in a sense are high risk. It provided a recognition for the special services of doctors of podiatric medicine as equivalent to the services provided by other practitioners. What we fail to recognize many times is that Congress, as representatives of the people, projected a need for podiatric care in this particular entitlement program. It provides a scope of practice for podiatrists that is governed by state law, which also is a mandate of the people. The individual state practice acts are again the will of the people through their state legislatures, which established the need and recognition for podiatric care. The system designed by Medicare provides for fiscal intermediaries, who are the insurance carriers that administer the program. Each carrier then establishes its own guidelines to deal with the medical policies of the program. The local guidelines for each state or area are additional documents that need to be reviewed for local modifications of the Medicare regulations. There are four options for patient payment: assignment, direct payment by the patient, billing the patient followed by patient payment upon receipt of his or her Medicare payment, or the selection of a health maintenance organization or similar private insurance option. Under this fourth option, the patient gives up his or her right to direct podiatric care, which is clearly a violation of the intent of the legislation that added podiatric medicine to Medicare in 1967. Given the changes that take place in any system, the original intent of Medicare was to provide an availability and access for podiatric care as required by the patient. To modify the system to change that intent without a change in law is morally, ethically, and legally questionable. PMID- 8481887 TI - Ulcer therapy. AB - The geriatric patient is at risk for many podiatric conditions. Ulcers can become chronic and life-threatening in this population if not treated properly. Treatment for ulcers is based on an understanding of anatomy and physiology. This article is meant to be used as a guide for the podiatrist serving the elderly population. PMID- 8481888 TI - Physiological pharmacokinetics and cancer risk assessment. AB - There has been considerable progress in recent years in developing physiological models for the pharmacokinetics of toxic chemicals and in the application of these models in cancer risk assessment. Physiological pharmacokinetic models consist of a number of individual compartments, based on the anatomy and physiology of the mammalian organism of interest, and include specific parameters for metabolism, tissue binding, and tissue reactivity. Because of the correspondence between these compartments and specific tissues or groups of tissues, these models are particularly useful for predicting the doses of biologically active forms of toxic chemicals at target tissues under a wide variety of exposure conditions and in different animal species, including humans. Due to their explicit characterization of the biological processes governing pharmacokinetic behaviour, these models permit more accurate predictions of the dose of active metabolites reaching target tissues in exposed humans and hence of potential cancer risk. In addition, physiological models also permit a more direct evaluation of the impact of parameter uncertainty and inter-individual variability in cancer risk assessment. In this article, we review recent developments in physiologic pharmacokinetic modeling for selected chemicals and the application of these models in carcinogenic risk assessment. We examine the use of these models in integrating diverse information on pharmacokinetics and pharmacodynamics and discuss challenges in extending these pharmacokinetic models to reflect more accurately the biological events involved in the induction of cancer by different chemicals. PMID- 8481889 TI - Enhancement of gap junctional intercellular communication in tumor promoter treated cells by components of green tea. AB - Green tea (Camellia sinensis) has been reported to inhibit tumor promotion in vivo and in vitro. Many tumor promoters inhibit gap junctional intercellular communication (GJIC) which may be an important mechanism of promotion. In the present study, we hypothesized that green tea would enhance GJIC in promoter treated cells. An aqueous extract of green tea (GTE) and several of its constituents were tested for their effects on GJIC in p,p' dichlorodiphenyltrichloroethane (DDT)-, 12-O-tetradecanoylphorbol-13-acetate (TPA)- and dieldrin-treated WB-F344 rat liver epithelial cells. All three promoters inhibited GJIC in a dose-responsive manner at non-cytolethal concentrations. (GTE (10-80 gamma/ml) enhanced GJIC 20-80% in promoter-treated cells. (-)-Epigallocatechin gallate and (-)-epicatechin gallate also enhanced GJIC in DDT-treated cells, but no effects were seen with (+)-catechin, (-) epicatechin, (-)-epigallocatechin, caffeine, or theobromine. These data suggest GTE may inhibit tumor promotion by enhancing GJIC and that the most active components are the catechin gallates. PMID- 8481890 TI - Relationships between oestrogen-inducible proteins, oestradiol and electrolyte ratio in breast cyst fluid. AB - Women who have breast cysts with intracystic Na+/K+ < 3 may have a higher risk of developing breast cancer than women who have breast cysts with intracystic Na+/K+ > 3. In this study wide-ranging intracystic concentrations of cathepsin D and pS2 (oestrogen inducible proteins/polypeptides) as well as oestradiol were found. The concentrations of cathepsin D and oestradiol were significantly higher in the low electrolyte ratio cyst group than in the high electrolyte ratio cyst group. No significant difference was found between pS2 concentrations in the two groups. The significantly higher intracystic concentrations of cathepsin D, a mitogenic lysosomal endopeptidase and oestradiol in the low electrolyte ratio group may partly provide an explanation for the higher risk of breast cancer which has been observed in this group of women. PMID- 8481891 TI - Antileukemic effects of non-metabolizable derivatives of spermidine and spermine. AB - To determine whether non-metabolizable derivatives of spermidine and spermine exert anticancer effects, L1210 leukemic mice were treated with 5,8 dimethylspermidine and 5,8-dimethylspermine. Both derivatives cured 5% of the leukemic mice. The increase in median survival time, however, was slight. In combination with alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, only 5,8-dimethylspermine had a favorable effect. Treatment with DFMO is known to increase the uptake of extracellular polyamines and presumably their derivatives, by depleting the intracellular putrescine and spermidine content. However, treatment of L1210 leukemia cells in vitro with DFMO did not affect the uptake of the methyl-substituted polyamines added to the growth medium. 5,8 Dimethylspermidine and 5,8-dimethylspermine repressed the ornithine decarboxylase activity when added to cultures of L1210 leukemia cells. S-Adenosylmethionine decarboxylase activity was only repressed by 5,8-dimethylspermine. This finding may explain the potentiation by this derivative and not by 5,8 dimethylspermidine, of the antileukemic effect of DFMO. PMID- 8481892 TI - Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice. AB - The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (-) epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12 dimethylbenz[a]anthracene (DMBA) and promoted using croton oil was inhibited by the topical application of 100 mg/kg body weight (b.w.) of (-)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2-4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 microgram/ml of (-)-epicatechin, further highlighting its antiproliferative effect. PMID- 8481893 TI - Modulation of transferrin receptor expression by insulin and granulocyte macrophage colony stimulating factor in AML-193 leukemic cells. AB - The effects of insulin and granulocyte-macrophage colony stimulating factor (GM CSF) on the expression of transferrin receptors in AML-193 myeloid leukemia cell line were investigated. Insulin, alone or in combination with GM-CSF, caused an increase in surface transferrin receptors within 5 min. This increase was inhibited by hyperosmolarity but not by cycloheximide suggesting the involvement of receptor recycling from internal pools. In contrast, receptor increase after 18 h of incubation with insulin and GM-CSF was sensitive to cycloheximide indicating that long term effects of these growth factors are mediated through protein synthesis. These results may have implications on combined GM-CSF + antitransferrin receptor antibody therapy of leukemias. PMID- 8481894 TI - Dietary fat promotes mammary tumorigenesis in MMTV/v-Ha-ras transgenic mice. AB - The purpose of this study was to investigate the influence of dietary fat on mammary tumorigenesis in MMTV/v-Ha-ras transgenic mice. Female MMTV/v-Ha-ras transgenics were fed diets providing 0, 5 or 25% of calories from corn oil (CO). The mammary tumor incidence was 7% (0% CO), 36% (5% CO) and 52% (25% CO). Ras mRNA levels were increased in mammary tumors in the 25% CO group. The ras transgene was hypomethylated in mammary tumors, but not in liver or nontransformed mammary tissue. Mammary tumors expressed apolipoprotein E mRNA. Alterations in gene structure and expression in transgenic mice may suggest mechanisms by which dietary fat promotes mammary tumors. PMID- 8481895 TI - Tumor growth and adherence change the expression of macrophage Mac-2. AB - The galactose-specific animal lectin, Mac-2, has been identified in macrophage (M phi) membrane, cytoplasmic, and nuclear fractions. Flow cytometric analyses showed that there is a decrease in membrane Mac-2 during tumor growth. After 24-h adherence there was an increase in the number of normal host (NH) and tumor bearing host (TBH) Mac-2+ M phi. Immunoblot analyses of NH and TBH M phi identified changes in the subcellular localization of Mac-2. The increase in nuclear Mac-2 during tumor growth, and after prolonged adherence of NH and TBH M phi, correlates with an increase in M phi entering the late G1 phases of the cell cycle. Northern blot analyses showed an increase in Mac-2 mRNA during tumor growth, and an increase in NH and TBH M phi after 24-h adherence. Tumor growth is able to manipulate the immune system through M phi by causing a down-regulation in membrane Mac-2 and an up-regulation in intracellular Mac-2. NH and TBH M phi respond to adherence by expressing increased membrane and nuclear Mac-2, but TBH M phi response is lower. PMID- 8481896 TI - The androgen receptor status of neuroendocrine cells in human benign and malignant prostatic tissue. AB - Neuroendocrine (NE) cells containing neurosecretory granules, rich in various peptide hormones and biogenic amines, are components of the human prostate epithelium and prostatic adenocarcinomas. Neuroendocrine differentiation in prostatic adenocarcinomas has been associated with a poor prognosis and, following androgen withdrawal therapy, tumor cell populations have been observed to become enriched with NE cells. We assessed androgen receptor (AR) expression in NE cells in benign and malignant prostatic tissue using double-labeling immunocytochemistry with validated monoclonal antibodies to the AR and to chromogranin A (a generic NE marker). Neuroendocrine cells in benign and malignant prostatic tissue generally showed nuclear staining with AR. Some distinct AR-negative nuclei were observed in normal NE cells. In prostatic adenocarcinomas with extensive NE differentiation, a subpopulation of AR-negative NE cells was demonstrated. In conclusion, benign and malignant prostatic tissue contain both AR-positive and AR-negative NE cells that may have significance in regards to androgen-independent tumor growth and tumor progression. PMID- 8481897 TI - Inhibition of cell motility after nm23 transfection of human and murine tumor cells. AB - Abstract nm23 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. The cellular mechanisms by which the nm23 protein may directly or indirectly modulate the metastatic phenotype is not yet known. Because cell motility plays an essential role in metastatic dissemination, we have studied whether tumor cells transfected with nm23 complementary DNA have any alterations in their ability to migrate. Our results demonstrate that nm23 transfection inhibits the ability of murine melanoma and human breast carcinoma cells to migrate in response to serum or to defined factors such as platelet derived growth factor or insulin-like growth factor 1. Random, unstimulated cell motility was not depressed in the nm23 transfectants. The results suggest that the nm23 gene product may interact with intracellular molecules that are essential for stimulated cell motility in two different tumor cell systems. PMID- 8481898 TI - Footprinting of individual tumors and their variants by constitutive cytokine expression patterns. AB - We have examined the cytokine mRNA expression profile of six different human cell lines derived from Ewing sarcomas using polymerase chain reaction and found each to constitutively express a characteristic pattern. Furthermore, each cell line differed in the levels of secreted cytokines. We also analyzed the expression of several cytokines in murine UV-induced sarcomas and their heritably stable progressive variants. Each murine tumor also constitutively expressed a large number of cytokines, and in some cases, the more malignant variants differed from their parental tumors. These results demonstrate that tumors of the same type, and even in the same lineage, can have distinct cytokine expression and/or secretion profiles. Some cytokines may stimulate tumor growth while others may have antitumor effects. Cytokine therapy may be tailored depending upon the cytokine profile of the individual malignancy. PMID- 8481899 TI - Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation. AB - Tumor necrosis factor (TNF), a cytokine, and okadaic acid, a tumor promoter, strongly phosphorylated the same proteins, vimentin and heat shock protein 27, although their time courses were different. Human TNF-alpha at a concentration of 0.6 nM markedly stimulated transformation of BALB/3T3 cells initiated with 3 methylcholanthrene. The human TNF-alpha was about 1000 times more effective than the chemical tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13 acetate. TNF induced growth of v-Ha-ras transfected BALB/3T3 cells (Bhas 42 cells), whereas it did not induce growth of nontransfected BALB/3T3 cells. Okadiac acid induced mouse TNF-alpha from Bhas 42 and BALB/3T3 cells. The results suggest that a chemical tumor promoter induces the secretion of TNF-alpha from various cells. The TNF then acts as an endogenous tumor promoter in vivo. PMID- 8481900 TI - Amplification of cyclin genes in colorectal carcinomas. AB - The genetic status of cyclin genes was examined in a panel of 47 colorectal carcinoma cell lines. Cyclin D2 was found to be amplified in one tumor and cyclin E in another. In each of the two cases, the amplified cyclin gene was overexpressed at the protein or mRNA level. Cyclin D1, previously shown to be amplified in breast and other tumors, was not amplified in these cancers. These data suggest that a variety of cyclin genes can play a role in human tumorigenesis and that cyclins D2 and E are particularly important in a subset of colorectal neoplasms. PMID- 8481901 TI - Association of glyceraldehyde-3-phosphate dehydrogenase expression with cell motility and metastatic potential of rat prostatic adenocarcinoma. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression is increased in Dunning R-3327 rat prostatic adenocarcinoma cell lines relative to normal rat ventral prostate tissue. GAPDH expression closely correlates with cell motility of Dunning prostate cancer cell lines and accurately distinguishes cell lines with high metastatic potential from those with low metastatic potential. Increased GAPDH expression in the cancer cell lines is not simply related to increased growth rate, since rapidly proliferating normal prostate tissue did not exhibit elevated GAPDH expression. PMID- 8481902 TI - Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain. AB - Laminin is a large multidomain protein with diverse biological activities. We previously demonstrated that intact laminin as well as an A chain synthetic peptide (LamA2091-2108) stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation. Here we report that LamA2091-2108 increases t-PA production by the highly metastatic murine melanoma cell line B16F10, with no effect on the parental B16F1 line, which has a low metastatic capacity. Incubation of plasminogen with B16F10-conditioned medium results in direct activation of the zymogen to plasmin. Furthermore, following incubation of B16F10 cells with plasminogen, plasmin is eluted from the cell surface, suggesting that these cells contain binding sites for plasminogen/plasmin in close proximity to t PA binding sites. Quantitation of t-PA activity using the synthetic substrate Val Leu-Lys-p-nitroanilide indicates a minimal 10-fold increase in t-PA in the conditioned medium of B16F10 cells grown in the presence of LamA2091-2108, with no increased t-PA activity observed in B16F1-conditioned medium. Similar results were obtained in immunocapture experiments which are specific for t-PA antigen. In addition, B16F10 melanoma-associated t-PA catalyzes the plasminogen-dependent hydrolysis of laminin. Together these data suggest that degradation of basement membrane proteins by metastatic melanoma cells may release fragments (such as LamA2091-2108) which stimulate both the production and activity of metastasis associated proteinases such as t-PA, providing a mechanism for augmentation of the metastatic capacity of B16F10 melanoma cells. PMID- 8481903 TI - Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre-messenger RNA at ED-A, ED-B, and CS1 regions in human liver tumors. AB - The molecular diversity of fibronectin arises from alternative RNA splicing at regions termed ED-A, ED-B, and IIICS. We investigated the splicing patterns of fibronectin pre-mRNA at both ED-B and IIICS regions in various human liver tissues with an emphasis on the expression of the alternative cell adhesive site CS1 within the IIICS region. The relative abundance of the fibronectin mRNA containing the CS1 sequence was significantly increased in both fetal and cancerous liver tissues, although it was not affected in nonmalignant tissues with chronic hepatitis and cirrhosis. Similarly, the relative abundance of the fibronectin mRNA containing the ED-B region was also increased in both fetal liver and liver tumors, showing a close parallelism with the splicing pattern at the ED-A region. Immunohistochemical examination of cancerous liver tissues with monoclonal antibodies directed to the ED-A and ED-B segments revealed that the fibronectin isoforms containing these extra peptide segments were specifically deposited in the tumor nodules. Other genes encoding kininogen, gamma chain of fibrinogen, and beta-amyloid protein precursor, all of which had been shown to be alternatively processed, did not show any significant alteration in the splicing pattern in cancerous liver tissues. These results indicate that the alternative splicing of fibronectin pre-mRNA at the ED-A, ED-B, and IIICS regions is coordinately modulated in both fetal and cancerous liver tissues toward inclusion of the extra peptide segments and that not all but only selected genes are susceptible for "fine tuning" of alternative RNA splicing in cancerous liver tissues. PMID- 8481904 TI - Coordinate expression of N-myc 2 and insulin-like growth factor II in precancerous altered hepatic foci in woodchuck hepatitis virus carriers. AB - Over 50% of the hepatocellular carcinomas (HCCs) arising in the livers of woodchucks with persistent woodchuck hepatitis virus (WHV) infection contain integrations of WHV DNA within, or immediately adjacent to, a unique and functional N-myc 2 retroposon [G. Fourel et al., Nature (Lond.), 347: 294-298, 1990; Y. Wei et al., J. Virol., 66: 5265-5276, 1992]. The integrations are believed to activate the expression of N-myc 2 by an enhancer insertion mechanism [Y. Wei et al., J. Virol., 66: 5265-5276, 1992]. Since the fetal growth factor insulin-like growth factor II (IGF-II) is also expressed in woodchuck HCCs [X. X. Fu et al., J. Virol., 62: 3422-3430, 1988; D. Yang and C. E. Rogler, Carcinogenesis (Lond.), 12: 1893-1901, 1991] we sought to determine the earliest stage in hepatocarcinogenesis at which overexpression of N-myc and IGF-II could be detected. The earliest precancerous lesions so far identified in woodchucks are altered hepatic foci (AHFs) [K. Abe et al., Jpn. J. Cancer Res., 79: 466-472, 1988; H. Popper et al., Hepatology (Baltimore), 1: 91-98, 1981]. Using in situ hybridization, we have demonstrated that both the N-myc and IGF-II genes are coordinately overexpressed in nearly all AHFs in precancerous woodchuck livers. In contrast, WHV replication was either repressed or undetectable in the same AHFs. The use of probes selective for N-myc 2 versus N-myc 1 (the normal mammalian homologue) revealed nearly exclusive expression of N-myc 2 in AHFs. Cells within AHFs were generally slow growing, as determined by frequency of histone III-expressing hepatocytes; however, a few fast-growing AHFs, with growth rates nearly equivalent to those of HCCs, were identified. Furthermore, very highly elevated N-myc 2 or IGF-II expression was detected in a few subregions within AHFs which otherwise exhibited a uniformly moderate expression, suggesting that selection for higher levels of N-myc or IGF-II expression may occur within AHFs. These data suggest that coordinate expression of N-myc 2 and IGF-II and repression of WHV replication may be functionally involved in the development of AHFs and that cells expressing very high levels of N-myc and IGF-II may be selectively enriched as AHFs progress to HCC, since high levels of N-myc and IGF II are common in HCCs. PMID- 8481905 TI - Roles of human hepatic and pulmonary cytochrome P450 enzymes in the metabolism of the environmental carcinogen 6-nitrochrysene. AB - 6-Nitrochrysene is remarkably tumorigenic in the lung and liver of newborn mice and approximates the activities of certain ultimate carcinogenic metabolites of polycyclic aromatic hydrocarbons. Previous studies have indicated that the major metabolic activation pathway of 6-nitrochrysene in newborn mice is initially through the formation of the proximate tumorigen trans-1,2-dihydro-1,2-dihydroxy 6-aminochrysene with subsequent formation of 1,2-dihydroxy-3,4-epoxy-1,2,3,4 tetrahydro-6-aminochrysene. In order to provide information on the possible risk associated with human exposure to 6-nitrochrysene, the ability of human hepatic and pulmonary microsomes to metabolize 6-nitrochrysene was investigated. The major metabolites identified in 11 hepatic microsomes were trans-1,2-dihydro-1,2 dihydroxy-6-nitrochrysene, trans-9,10-dihydro-9,10-dihydroxy-6-nitrochrysene, trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene, 6-aminochrysene, and chrysene 5,6-quinone. Following the incubations of 6-nitrochrysene with 11 different human pulmonary microsomes, qualitatively similar metabolic patterns were obtained, although quantitative differences were evident. These results demonstrated that human liver and lung are capable of metabolizing 6-nitrochrysene to known potent carcinogenic metabolites via ring oxidation and nitroreduction. In an attempt to define the roles of individual human hepatic P450 involved in the metabolism of 6 nitrochrysene, the catalytic activities known to be associated with a specific P450 were analyzed and compared with the levels of each metabolite of 6 nitrochrysene formed with the same microsomes. Rates of phenacetin O-deethylation (P450 1A2) and nifedipine oxidation (P450 3A4) were well correlated with the rates of formation of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6 aminochrysene, respectively. Inhibition studies with specific P450 inhibitors and antibodies further support the view that P450 1A2 and P450 3A4 are the major forms responsible for the formation of trans-1,2-dihydro-1,2-dihydroxy-6 nitrochrysene and 6-aminochrysene, respectively, in human liver. Further metabolism of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene appears to require P450 3A4. In the human lung, P450 1A1 appears to play a major role in the metabolism of 6-nitrochrysene to trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene. These results provide some requisite knowledge for evaluating human susceptibility to 6-nitrochrysene. PMID- 8481906 TI - Coexpression of messenger RNA for TRK protooncogene and low affinity nerve growth factor receptor in neuroblastoma with favorable prognosis. AB - Nerve growth factor (NGF), essential for differentiation and survival of sympathetic neurons is suggested to play a role in differentiation or regression of neuroblastoma. Expression of mRNA for the trk protooncogene, encoding a tyrosine kinase receptor essential for functional NGF signal transduction, and mRNA for the low affinity NGF receptor (LNGFR) was examined in 45 neuroblastomas and 3 benign ganglioneuromas using Northern blot analysis. Expression of trk mRNA and LNGFR mRNA correlated with young age, favorable clinical stages, and absence of N-myc amplification. All children (n = 19) with neuroblastomas coexpressing mRNA for trk and LNGFR are alive 8-84 months from diagnosis, regardless of age and stage. In contrast, no child (n = 15) with tumor lacking trk mRNA is alive without disease. Three subsets of patients were distinguished, one favorable (trk+, LNGFR+, n = 19, 100% survival probability), one intermediate (trk+, LNGFR , n = 11, 62.3% survival probability), and one unfavorable (trk-, LNGFR +/-, n = 15, 0% survival probability, P < 0.001). In widespread neuroblastoma stage IVS prone to spontaneous regression, three tumors coexpressing trk and LNGFR mRNAs regressed after no or minimal therapy while the remaining tumor expressing trk but not LNGFR mRNA progressed to a fatal outcome. It is concluded that neuroblastomas coexpressing mRNA for both NGF receptor subtypes are favorable tumors likely to differentiate or regress spontaneously or respond to conventional therapy. It is further hypothesized that loss of functional NGF receptors is an important step in tumorigenesis of undifferentiated malignant childhood neuroblastoma. For these unfavorable tumors current therapy remains futile and first-line innovative therapy is justified. PMID- 8481907 TI - Inhibition of doxorubicin-induced apoptosis in vivo by 2-deoxy-D-glucose. AB - Previous studies have shown that DNA cleavage by mammalian topoisomerase II is ATP dependent and can be inhibited by metabolic inhibitors. Furthermore, it has been shown that metabolic inhibitors also have a cytoprotective effect in vitro against topoisomerase II-targeting antitumor drugs. However, the nature of the ATP-dependent process is not known. We have previously shown that doxorubicin induces apoptosis (programmed cell death) in the murine small intestine which can be inhibited by the protein synthesis inhibitor cycloheximide. In the present study, we have demonstrated that 2-deoxy-D-glucose reduces the incidence of doxorubicin-induced apoptosis in vivo if administered within 45 min of the doxorubicin. Maximum reduction was observed at 2 h after treatment (approximately 66%); however, significant reduction was still observable at 9 h after treatment (approximately 33%). Significant positive correlation was observed between protein synthesis inhibition and apoptosis inhibition. Other possible mechanisms of action of the inhibitor do not appear to be important in cytoprotection. The inhibitor did not reduce the uptake of doxorubicin into the intestinal epithelium; however, it caused a significant increase in retention of the drug. The kinetics of inhibition suggest that alteration of cell cycle kinetics, inhibition of formation of doxorubicin-topoisomerase II complex or induction of glucose-regulated proteins are not significant factors in cytoprotection. These studies indicate that at least in the mouse small intestinal epithelium, the ATP dependent process in cell killing by doxorubicin may involve protein synthesis. PMID- 8481908 TI - Plasma pharmacokinetics of vinblastine and the investigational Vinca alkaloid N (deacetyl-O-4-vinblastoyl-23)-L-ethyl isoleucinate in mice as determined by high performance liquid chromatography. AB - The plasma pharmacokinetics of vinblastine and N-(deacetyl-O-4-vinblastoyl-23)-L ethyl isoleucinate (VileE) in mice have been studied as part of the preclinical investigations of VileE, a new investigational semisynthetic Vinca alkaloid. Groups of animals received the test compounds through i.v. bolus injection at LD10, 0.5 x LD10, and 0.1 x LD10 doses. VileE has also been administered p.o. Drug plasma levels have been analyzed with a sensitive and selective method using liquid-liquid extraction for sample clean-up and high-performance liquid chromatography combined with fluorescence detection for quantification. Following i.v. injection, plasma kinetics of both vinblastine and VileE can be described adequately by a three-compartment open model. VileE demonstrates nonlinear pharmacokinetics with decreasing clearance and increasing terminal half-lives at increasing doses. Comparison of the plasma concentration versus time curves for vinblastine in humans and mice indicates that the toxicity of these compounds may not be directly related to the drug exposure expressed by the area under curve in plasma but by the terminal half-life and the time that a toxic threshold level is attained. Pharmacokinetically guided dose escalation in coming phase I trials of VileE is, therefore, discouraged. PMID- 8481909 TI - Growth inhibition of hormone-responsive and -resistant human breast cancer cells in culture by N1, N12-bis(ethyl)spermine. AB - Previous studies have documented differential sensitivity of human lung cancer and melanoma cell lines to the cytotoxic effects of N1, N12-bis(ethyl)spermine (BESpm). We show here that BESpm can significantly inhibit the growth of six human breast cancer cell lines with 50% inhibitory concentration in the microM range. The degree of inhibition does not correlate with estrogen receptor status. Detailed studies with estrogen receptor-positive MCF-7 and estrogen receptor- negative Hs578t cells show a similar dose-response curve with concentrations of 1 10 microM resulting in maximal growth inhibition. Growth inhibition in both lines is associated with an 8-12-fold induction of the polyamine catabolic enzyme, spermidine/spermine N1-acetyltransferase, and a progressive decrease in intracellular polyamine levels over 6 days even though steady-state levels of BESpm are achieved within 24 h. Similar studies on WTMCF7 and AdrRMCF7 cells show that the acquisition of resistance to hormonal or doxorubicin therapy is not associated with resistance to the growth-inhibitory effects of BESpm. These results suggest that BESpm exerts similar growth-inhibitory effects against both hormone-responsive and -unresponsive human breast cancer cells, a finding which has significance for the potential use of polyamine analogues in treating human breast cancer. PMID- 8481910 TI - Influence of vascular thermotolerance on the heat-induced changes in blood flow, pO2, and cell survival in tumors. AB - Vascular thermotolerance in SCK tumors of A/J mice was studied by comparing the changes in blood flow, as measured by the 86Rb uptake method, from a single heating with those from two heatings. The heat-induced decline in 86Rb uptake in tumors could be substantially inhibited when the tumors were preheated, indicating the development of vascular thermotolerance. In SCK tumors, the vascular thermotolerance peaked 5 or 18 h after the tumors were heated for 1 h at 41.5 degrees C or 42.5 degrees C, respectively. Consequently, the tumor blood flow decreased by 50% in 81 min when the tumors were heated at 43.5 degrees C without preheating, whereas the tumor blood flow decreased by 50% in 195 min at 43.5 degrees C when the tumors were preheated 18 h earlier at 42.5 degrees C for 1 h. The influence of vascular thermotolerance on the heat-induced changes in intratumor pO2 was also investigated. The average intratumor pO2 was 8.9 mm Hg before heating. Heating at 43.5 degrees C or 44.5 degrees C for 1 h dramatically decreased the intratumor pO2 to 3.0 or 1.2 mm Hg, respectively. However, the intratumor pO2 decreased to 6.6 or 3.8 mm Hg when the tumors were heated at 43.5 degrees C or 44.5 degrees C, respectively, 18 h after preheating at 42.5 degrees C for 1 h. Heating the tumors when tumor vasculatures were at peak thermotolerance was relatively ineffective in suppressing tumor growth. The data demonstrate that vascular thermotolerance in tumors may exert profound effects on tumor response to multiple heatings in clinical hyperthermia. PMID- 8481911 TI - The spatial distribution of immunotoxins in solid tumors: assessment by quantitative autoradiography. AB - The spatial distribution of i.v. administered immunotoxins in s.c. human rhabdomyosarcoma RD2 xenografts was studied. The toxin and immunotoxins were: (a) diphtheria toxin (DT); (b) a binding-deficient form of DT (CRM107) linked to a monoclonal IgG1 antibody (454A12) directed against the human transferrin receptor (454A12-107); (c) the binding-deficient form of DT linked to the Fab' fragment of 454A12 (Fab'-107); and (d) the binding-deficient form of DT coupled to MOPC21, a monoclonal IgG1 with no significant binding to RD2 cells. DT and the immunotoxins were radiolabeled with 125I and injected via the tail vein into tumor-bearing athymic mice (median tumor weight, 0.25 g). Tumors were removed 2, 6, and 24 h after injection of DT or immunotoxin. Film images of 20-microns frozen sections were digitized by video microscopy, and gray levels were converted to tissue concentrations based upon the film response to radioactivity standards and the specific activity of the radiolabeled toxins. Images of the tumors were characterized quantitatively by the kurtosis and the area above threshold; the kurtosis is a measure of the spatial heterogeneity of the radiolabeled immunotoxins, and the area above threshold is defined here as the fractional tumor area that reaches or exceeds 1.5% of the initial plasma concentration. The spatial distribution of DT in the tumors was extremely uniform, characterized by low kurtosis values. In contrast, the autoradiograms of 454A12-107 were punctate in appearance and were characterized by very high kurtosis values. Fab'-107, which has approximately one-half the molecular weight of the intact immunotoxin and binds only monovalently, also produced punctate images with kurtosis values similar to those for 454A12-107. The nonbinding immunotoxin distributed somewhat less uniformly than DT but much more homogeneously than either of the binding immunotoxins. DT, 454A12-107, and Fab'-107 have similar affinities for their respective receptors, but the concentration of binding sites for DT on RD2 cells (<3,000 receptors/cell) is much lower than the concentration of transferrin receptor (60,000 receptors/cell). Thus, the heterogeneous distribution of 454A12 107 and Fab'-107 probably reflects retarded penetration due to binding to the tumor cells. The area above threshold was greatest for DT and lowest for 454A12 107; the fragment and nonbinding immunotoxins had intermediate values. The lower area above threshold for the nonbinding immunotoxin as compared with DT may be due to the considerably large molecular weight and hence the lower capillary permeability and diffusion coefficient of the immunotoxin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481912 TI - Induction of differentiation in myeloid leukemia cell lines and acute promyelocytic leukemia cells by liposomal all-trans-retinoic acid. AB - All-trans-retinoic acid (ATRA) induces complete remissions in the majority of patients with acute promyelocytic leukemia. Despite continuous p.o. ATRA administration, many patients relapse after a short remission duration. In these patients, ATRA plasma concentrations were found to be very low, which was related to induction of retinoic acid-binding protein and increased drug catabolism by cytochrome P-450-mediated reactions. An i.v. ATRA formulation, which can be achieved by encapsulating ATRA into liposomes, may have the potential to overcome these unwanted effects. We investigated the ability of liposomal ATRA (L-ATRA) to induce differentiation of human myeloid leukemia cell lines (HL-60, KG-1, and THP 1). Cellular differentiation, as assessed by morphological criteria and by the expression of a mature myeloid cell surface antigen (CD11b on HL-60 and KG-1 cells), was induced by culture in the presence of L-ATRA. The ability of L-ATRA treated HL-60 cells to reduce nitroblue tetrazolium demonstrated that they were functionally differentiated cells. Cell cycle analysis revealed significant growth inhibition of the cells after L-ATRA treatment. Following culture with L ATRA, cells from five patients with acute promyelocytic leukemia were found to be morphologically and immunophenotypically mature myeloid cells. L-ATRA was as effective as free ATRA in inducing differentiation of the cell lines and of the cells from patients with acute promyelocytic leukemia. We conclude that L-ATRA effectively induces differentiation and may be a useful parenteral ATRA formulation for overcoming the pharmacological mechanisms that lead to "retinoid resistance." PMID- 8481913 TI - Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms. AB - Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8481914 TI - Genetic construction, expression, and characterization of a single chain anti carcinoma antibody fused to beta-lactamase. AB - We report the genetic construction and expression of a fusion protein between an antibody single chain-linked variable domain fragment specific for human carcinomas and beta-lactamase II from Bacillus cereus. Sequences encoding the variable regions of the L6 monoclonal antibody were assembled so as to be separated from each other by an 18-amino acid linker and from the mature form of beta-lactamase by a 6-amino acid linker. The construct was placed under the transcriptional regulation of the lac promoter, and the PelB signal sequence was used to direct export of the fusion protein to the periplasmic space of Escherichia coli. After induction, biologically active material was recovered from both culture supernatants and cell lysates. Affinity chromatography yielded about 2.5 micrograms of protein/ml of initial culture volume. The fusion protein was shown to bind to tumor cells at least as well as chemically prepared F(ab') and to maintain beta-lactamase activity at a level similar to that of the native enzyme. Tumor cells coated with the fusion protein were sensitive to a cephalosporin mustard prodrug in a dose-dependent fashion comparable to that of enzyme chemically conjugated to F(ab'). This article demonstrates the feasibility of using single chain-linked variable domain-enzyme fusion proteins for the activation of anticancer prodrugs. PMID- 8481915 TI - p53 mutation is a common genetic event in ovarian carcinoma. AB - Using the single-strand conformational polymorphism technique, we have screened 66 malignant ovarian tumors for p53 mutation in exons 5 to 8. Thirty-four of the tumors demonstrated a single-strand conformational polymorphism band shift in this region of the gene, including 6 in exon 5, 7 in exon 6, 12 in exon 7, and 10 in exon 8 (one of the tumors showed a shift for exons 7 and 8). All of the single strand conformational polymorphism shifts have been further characterized by DNA sequencing, and 31 of 35 have been shown to represent genuine DNA alterations. These include 27 point mutations (23 missense, 2 nonsense, and 2 silent mutations), 3 deletions (a 2-base pair deletion introducing, by frameshift, a stop codon further downstream; a 3-base pair deletion; and an unusual 6-base pair deletion made up of separate 2-base pair and 4-base pair deletions), and a 4-base pair insertion (introducing a stop codon downstream). In total, 29 of the 66 (44%) carcinomas analyzed had mutations affecting the primary sequence of the p53 protein. p53 mutation was found in tumors of all International Federation of Gynecologists and Obstetricians stages, suggesting that it might be an earlier genetic event in the progression of epithelial ovarian tumors than previously thought. A significantly greater number of p53 mutations were seen in high-grade serous carcinomas than in those of endometrioid and mucinous types (0.02 > P > 0.01). Analysis of the distribution of point mutations showed no preference for any particular mutation type. PMID- 8481916 TI - Effects of cisplatin on the induction of apoptosis in proliferating hepatoma cells and nonproliferating immature thymocytes. AB - A 2-h exposure of JB1 rat hepatoma cells in late log phase of growth to 50 microM cis-diamminedichloroplatinum (II) (cisplatin) resulted in the asynchronous detachment of cells from the monolayer over 4 days. Detached but not monolayer cells exhibited condensed chromatin and DNA fragmentation, which is indicative of endonuclease activation, the hallmarks of apoptosis in epithelial cells. The number of cisplatin-treated cells identified as apoptotic at any one time was never > 1% of the total cell number present on addition of drug. Two days after drug addition there was a decrease from 85% to 29% cells in G1 phase of the cell cycle, cells in S phase increased from 9% to 18%, and cells in G2/M phase increased from 6% to 51% with respect to untreated cells. Previous studies by Eastman and colleagues demonstrated that cisplatin-induced apoptosis of Chinese hamster ovary cells occurred in the G2 phase of the cell cycle [A. Eastman, Cancer Cells (Cold Spring Harbor), 2: 275-280, 1990]. Continuous exposure of JB1 cells to cycloheximide (1 microM) during and after exposure to cisplatin prevented both drug-induced changes in cell cycle distribution and the engagement of apoptosis. Freshly isolated immature rat thymocytes are known to be exquisitely sensitive to the induction of apoptosis by multiple stimuli including dexamethasone, etoposide, and irradiation. However, no significant increase in the amount of apoptosis above control levels was observed up to 36 h after a 2-h exposure to 50 microM cisplatin. JB1 cells have a doubling time of 24 h, whereas > 90% of immature rat thymocytes are noncycling. The data presented here provide indirect evidence that initiation of cisplatin-induced apoptosis may need to be coupled to a cell cycle-mediated event. PMID- 8481917 TI - Chromosome abnormalities in eighty-three head and neck squamous cell carcinomas: influence of culture conditions on karyotypic pattern. AB - Short-term cultures from 115 squamous cell carcinomas (SCC) of the head and neck were cytogenetically investigated. Thirty-six of the tumors have been reported previously, whereas 79 are new cases. The material was divided into two series based on the medium used. The 80 tumors of series I were cultured in RPMI 1640 supplemented with fetal calf serum, glutamine, antibiotics, insulin, cholera toxin, and epidermal growth factor. The 35 tumors of series II were cultured in a chemically defined, serum-free medium with a low calcium concentration, MCDB 153, which stimulates epithelial growth while inhibiting fibroblasts. A total of 83 tumors with clonal karyotypic abnormalities were detected in the two series. Series II had a higher proportion of tumors with complex karyotypic changes than series I (43% versus 15%), a lower proportion of tumors with pseudo- or neardiploid clones characterized by simple rearrangements (3% versus 34%), and a lower frequency of unrelated clones (3% versus 24%), indicating that the different culture conditions favored growth of different cell populations. Except for rearrangements of 1p22, which were mainly found in series I, the distribution of breakpoints in structural aberrations was similar in the two series and clustered to several chromosomal bands or regions, in particular 11q13, 1p22, 1p11-12, 3p11-q11, 5q13, 1q25, 15q10, and 8q10. Unbalanced structural aberrations were more common in series II, frequently leading to loss of segments from chromosome arms 3p, 7q, 8p, 11q, 13p, 14p, and 15p, whereas gain of genetic material often involved chromosome arms 1q, 3q, 8q, and 15q. PMID- 8481918 TI - Baculovirus recombinants expressing the human carcinoembryonic antigen gene. AB - Carcinoembryonic antigen (CEA), one of the most extensively studied human tumor associated antigens, represents a potential target for passive as well as active immunotherapy. We describe here the first baculovirus recombinants expressing the human CEA gene. Eight baculovirus clones were isolated which expressed products of varying molecular weights; one clone, termed BVCEA-140, was shown to contain multiple CEA epitopes by reactivity to a panel of anti-CEA monoclonal antibodies. When purified protein isolated from this clone was deglycosylated, immunoreactive species ranging from M(r) 50,000 to M(r) 110,000 were found. Results of Southern blot analysis carried out on BVCEA-140 DNA were consistent with the hypothesis that these products result from the stable expression of variants which have recombined within the repeated domains of CEA. Other baculovirus recombinants expressing products comprising different portions of the CEA gene were also derived. One, termed BVCEA-35, was shown to be a recombination between the first 87 bases of domains I and III of the CEA gene. A variant, termed BVCEA-16, contained only the NH2-terminal domain of the CEA gene. Moreover, a recombinant expressing the closely related molecule nonspecific cross-reactive antigen was also derived. As shown here, commercially available preparations of CEA, which are derived from tumor biopsies or cell line supernatants, may contain nonspecific cross-reacting antigens and other contaminants. Thus, the recombinant CEA molecules described should have numerous uses including validation of the use of monoclonal antibodies as standards in CEA serum assays, the characterization of immune responses to CEA, the use as immunogen, and the study of structure function relationships. PMID- 8481919 TI - Transforming growth factor-alpha expression produces only morphological transformants of diploid human fibroblasts. AB - Transforming growth factor-alpha (TGF-alpha) is a potent mitogen for a variety of epithelial and mesenchymal cells and is commonly expressed in many human tumors and tumor cell lines. Frequently, this creates a potential autocrine circuit for growth stimulation in these cells; however, this is occurring in a background of other mutation-generated events. To determine the significance of the TGF-alpha circuit alone, we expressed the human TGF-alpha cDNA in a diploid human foreskin fibroblast strain, 7-25, under the control of the cytomegalovirus immediate early promoter-enhancer region and screened transfectants for TGF-alpha expression by Northern analysis and by immunoprecipitation. Partially processed forms (M(r) 24,000 and 20,000) of the recombinant TGF-alpha were observed in cell lysates and a M(r) 5500 fully processed form was secreted by the fibroblasts into the media. TGF-alpha-expressing clones showed an altered morphology and an increased saturation density (1.4- to 2.1-fold) but did not exhibit anchor-age-dependent growth in soft agarose or the ability to form tumors in nude mice. Additionally, expression of recombinant TGF-alpha did not extend the lifespan of these fibroblast clones. Scatchard analysis revealed approximately 10(5) epidermal growth factor (EGF) receptors on the surface of these human fibroblasts, indicating that the failure of TGF-alpha expression to strongly transform these cells is not due to low EGF receptor levels. These data suggest that cell type plays an important role in determining the transforming ability of TGF-alpha. PMID- 8481920 TI - Fibroblast growth factor 4 transfection of MCF-7 cells produces cell lines that are tumorigenic and metastatic in ovariectomized or tamoxifen-treated athymic nude mice. AB - Successful antiestrogen treatment in patients with tamoxifen-responsive breast tumors is often followed by an outgrowth of tumors cells that are antiestrogen resistant, implying that estrogen-dependent tumors can become estrogen independent. In an effect to mimic this progression, we have transfected fibroblast growth factor 4 into MCF-7 cells, a human breast carcinoma cell line that is estrogen-dependent for growth in nude mice. This transfection results in cell lines that form progressively growing, metastatic tumors when injected s.c. into untreated or tamoxifen-treated ovariectomized nude mice. In contrast to the parental cell line, growth of transfected cells in ovariectomized nude mice is stimulated by tamoxifen treatment and inhibited by estrogen treatment of the mice. Parental MCF-7 cells were transfected with an expression vector for beta galactosidase, conferring the ability to convert the chromogenic substrate, 5 bromo-4-chloro-3-indoyl-beta-galactoside, to a blue color and allowing the detection of their presence within tumors developing after coinoculation with fibroblast growth factor 4-transfected cells. The fibroblast growth factor 4 transfected cells could support growth and metastasis of the beta-galactosidase expressing parental cell line when both lines were coinjected into the same site in untreated or tamoxifen-treated, ovariectomized mice. These data suggest a possible role for fibroblast growth factors in the progression of breast tumors to an estrogen-independent, antiestrogen-resistant, metastatic phenotype. They also support a role for paracrine factors in mixed populations of tumor cells of differing states of malignant progression. PMID- 8481921 TI - Quantitative demonstration of spontaneous metastasis by MCF-7 human breast cancer cells cotransfected with fibroblast growth factor 4 and LacZ. AB - We recently established transfectants of MCF-7 human breast cancer cells with fibroblast growth factor 4 (fgf-4) that showed rapid growth and spontaneous metastasis in ovariectomized and tamoxifen-treated nude mice. To establish a spontaneous metastatic model of human breast cancer cells in nude mice with a sensitive marker for detection of micrometastasis, the transfection of fgf-4 was combined with transfection of the bacterial lacZ gene encoding beta galactosidase. MKL-4 cells, a lacZ transfectant of an fgf-4-transfected cell line, showed the same level of fgf-4 expression as parental cells and expressed a high level of beta-galactosidase activity. When MKL-4 cells were injected s.c. into female nude mice, rapidly growing tumors developed. Whole organ staining for beta-galactosidase activity was able to detect even small numbers of metastatic tumor cells. Micrometastases in lymph nodes, lung, and brain were detected 3 weeks after the tumor cell injections, the first time point tested. Within 12 weeks, metastases were observed in lymph nodes, lung, brain, kidney, perirenal fatty tissues, liver, spleen, retroperitoneum, heart, and gallbladder. The frequency of metastasis and number of foci were correlated with the volume of the primary tumors. The distribution of metastatic sites was similar to that in breast cancer patients. MKL-4 cells may be a useful model for studying the malignant progression of hormone-dependent breast cancer, antimetastatic drugs, or early events in metastasis. PMID- 8481922 TI - Correspondence Re: H. Nagasawa and J. B. Little, Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res., 52: 6394-6396, 1992. PMID- 8481923 TI - Environmental carcinogenesis and its prevention: the head and neck cancer model. PMID- 8481924 TI - Fourth annual Pezcoller Symposium--adhesion molecules: cellular recognition mechanisms. PMID- 8481925 TI - Menstrual effects on surgical treatment for breast cancer. PMID- 8481926 TI - Diagnosis and treatment of spinal cord compression in malignant disease. PMID- 8481927 TI - Diagnosis and management of malignant pleural effusion. PMID- 8481928 TI - Prospects for gene-directed therapy with antisense oligodeoxynucleotides. PMID- 8481929 TI - Impact of adjuvant chemotherapy in breast cancer on response to tamoxifen at relapse. AB - A series of 105 patients with operable breast cancer previously entered in the WMOA adjuvant therapy trials were reviewed in order to assess methods of treatment on relapse and subsequent patterns of relapse and survival, related to previous adjuvant therapy. Tamoxifen was the predominant medical therapy offered on relapse. Unexpectedly, analysis of the relapse and survival data for these hormone-treated patients suggested that prior adjuvant therapy negatively influenced response to tamoxifen, with overall survival of treated and control patients being identical. Although not statistically significant, possible explanations of this trend have been explored. PMID- 8481931 TI - Effect of adjuvant systemic therapy on response to treatment after relapse. PMID- 8481930 TI - Response to chemotherapy after relapse in patients with or without previous adjuvant chemotherapy for breast cancer. The French Epirubicin Study Group. AB - The French Epirubicin Study Group undertook a retrospective study to evaluate the response rate at relapse, time to treatment failure, and overall survival according to previous CMF-type adjuvant chemotherapy in patients who had taken part in two successive clinical trials. The statistical significance of the comparisons was tested after adjustment for the factors that differed most between the two groups. Patients who had received previous adjuvant chemotherapy had a lower response rate (p = 0.03), a shorter time to treatment failure (p = 0.007), and shorter overall survival after relapse (p = 0.008); overall survival after initial diagnosis was not significantly different. With respect to patients with axillary node metastases at the time of diagnosis (N+ patients), those with previous adjuvant chemotherapy had a lower response rate (p = 0.01) and shorter time to treatment failure (p = 0.02), but overall survival after relapse and after initial diagnosis were not significantly different. This retrospective and descriptive study suggests that chemotherapy is less effective after relapse, as measured by response rate and time to treatment failure, in patients with previous adjuvant chemotherapy. PMID- 8481932 TI - Efficacy and tolerability of 4-hydroxyandrostenedione (4-OHA) as first-line treatment in postmenopausal patients with breast cancer after adjuvant therapy. AB - Aromatase inhibitors are known to be effective in the treatment of advanced postmenopausal breast cancer. To assess the efficacy of the aromatase inhibitor 4 hydroxyandrostenedione (4-OHA) as first-line treatment in patients who were either resistant to or had relapsed after adjuvant therapy, 50 eligible patients received intramuscular 4-OHA either 250 mg or 500 mg fortnightly until disease progression or severe adverse events. Of the 43 patients evaluable for clinical response (UICC criteria), 15 (36%) showed objective response (CR+PR), 6 (14%) stable disease (SD). In relation to disease site, objective responses were obtained in 55% of cases with soft tissue metastases (16/29); in 33% with visceral metastases (8/24), and in 24% with bone involvement (5/21). In relation to previous adjuvant treatment, there were eight objective responses among the 17 patients treated with chemotherapy (47%), and seven objective responses among the 24 treated with tamoxifen (29%). The treatment was well tolerated. These results support the hypothesis that adjuvant therapy, whether hormonal or chemotherapy, may make patients less responsive to subsequent treatment. PMID- 8481933 TI - Experience with aromatase inhibitors in the treatment of advanced breast cancer. AB - Inhibition of the aromatase enzyme system has become an established means of hormonal treatment for hormone-responsive advanced breast cancer. The widest clinical experience is with aminoglutethimide, which achieves around 30% objective remissions of metastatic disease for up to 1 year. Due to the sometimes serious side-effects of this drug, preclinical and clinical investigations have been undertaken and have yielded a number of steroidal and non-steroidal aromatase inhibitors that have been shown in early or mature clinical trials to give objective disease remissions similar to those with aminoglutethimide but with less toxicity. There is thus good reason to believe that newer aromatase inhibiting drugs will soon be available for routine use in patients with breast cancer. This paper summarizes our experience and reviews data from other groups. PMID- 8481934 TI - Cell biological factors associated with the response of breast cancer to systemic treatment. AB - A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficulty accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positively, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities. PMID- 8481935 TI - Use of endocrine therapy to study the biology of breast cancer. AB - Drug resistance is the main reason for therapeutic failure and death in breast cancer. In vitro investigations have identified some mechanisms that may be responsible for resistance to chemotherapeutic agents in breast cancer, but we know little about the mechanisms responsible for resistance to endocrine treatment in receptor-positive tumors. Accordingly, a major task for future studies is to explore the mechanisms of both primary and acquired resistance to endocrine treatment as well as to chemotherapy in breast cancer. Drug resistance may be related to alterations in endocrine as well as paracrine delivery of certain growth factors or hormones, but it may also be caused by alterations in drug disposition. Primary resistance may be evaluated by comparing the response to drug treatment with the expression of different biochemical parameters in the tumor before treatment. To explore the mechanisms of acquired drug resistance requires study of the changes in biological parameters developing over time during drug therapy. Also, it may be of interest to use certain drugs (like a 'classical' anti-estrogen and a steroidal anti-estrogen) in a particular sequence to explore the possibility of cross-resistance (or lack of it) between particular treatment modalities. Possible implications for the design of future trials in breast cancer treatment are discussed. PMID- 8481936 TI - Raised intracranial pressure, the syndrome of inappropriate antidiuretic hormone secretion, and arginine vasopressin in tuberculous meningitis. AB - Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mmHg, range 8.4-50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8-42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia. PMID- 8481937 TI - Cerebrospinal compensation in hydrocephalic children. AB - One hundred and fifteen cases of hydrocephalus in children were analysed. Cerebrospinal compensatory reserve was assessed by a computerized, constant rate, lumbar infusion test. Head circumference and ventricular size were measured and a psychometric examination carried out. A classification of hydrocephalus based on resting cerebrospinal fluid pressure (CSFP) and resistance to cerebrospinal fluid outflow (RCSF) was introduced. Parameters of compensatory reserve were compared in atrophy (low CSFP, low RCSF), normal-pressure hydrocephalus (low CSFP, increased RCSF), non-communicating hydrocephalus (high CSFP, low RCSF) and acute hydrocephalus (high CSFP and increased RCSF). Significant differences were found between the factors describing compensatory ability in these groups. Sixty-two patients could be classified on the basis of resting CSFP and RCSF. Differentiation between the types of hydrocephalus was shown to be more accurate when all variables measured during the pressure-volume test were considered. The patterns of the time courses of CSFP during rate infusion tests in the different types of hydrocephalus are presented. PMID- 8481938 TI - Arachnoid cyst of the lateral ventricles. PMID- 8481939 TI - Reflex seizures in Down syndrome. AB - A unique patient with Down syndrome who developed reflex seizures is described. The patient has had recurrent intermittent seizures for the past 3.5 years. These seizures were usually precipitated by auditory stimuli such as sudden loud noises. While having seizures the patient experienced severe discomfort in the posterior neck area. The seizures usually lasted 10-20 s, and there was no aura, nor was there a postictal phase. Of the numerous investigations performed, closed circuit electroencephalogram video telemetry was most helpful in arriving at an accurate diagnosis. Carbamazepine administration resulted in total seizure control and reflex stimuli no longer provoke seizure activity. Although it has been suggested that reflex seizures may be due to genetic factors or structural central nervous system defects, we were unable to uncover the cause of the reflex seizures in our patient. PMID- 8481940 TI - Circadian rhythm of glucose utilization in the pineal body of rats of different ages. AB - Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 mumol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging. PMID- 8481941 TI - Invasive character of an intradural spinal meningioma in early childhood. AB - The authors report the case of a 2-year-old baby girl with an intradural meningotheliomatous meningioma of the cauda equina which recurred three times. Despite four operative procedures and localized radiotherapy, the lesion kept on growing to reach the retroperitoneal space. Extensive laminectomy and associated radiotherapy were probably responsible for a spinal dislocation which had to be operated on. The child was left paraplegic with major bladder dysfunction after all procedures. This is the first reported case of well-documented "malignant" evolution of a spinal meningioma. PMID- 8481942 TI - Ependymomas of the filum terminale in childhood: report of four cases and review of the literature. AB - Four cases of ependymoma of the filum terminale occurring in childhood are reported. The clinical, therapeutic and prognostic features seen at this age and in adults were compared. PMID- 8481943 TI - Pathologic findings in a patient with a vein of Galen aneurysm treated by staged endovascular embolization. AB - Vein of Galen aneurysms are uncommon malformations that can be treated with a combination of endovascular embolization and surgery. Since the relevant techniques are new and innovative, their pathologic sequelae are not yet well described. A patient treated with staged embolization over a 15-month period developed evidence of cerebral venous hypertension on angiography. At necropsy, we observed marked myointimal proliferation of the aneurysm wall, dura, and cerebral vessels in addition to severe widespread encephalomalacia, calcinosis, and rare mural thrombi. These vascular changes have not been previously described in cases of vein of Galen aneurysm, and may, in part, be a consequence of embolization therapy. PMID- 8481944 TI - Pleomorphic xanthoastrocytoma associated with von Recklinghausen neurofibromatosis. AB - The authors present a case of pleomorphic xanthoastrocytoma that occurred in a 14 year-old boy with von Recklinghausen's neurofibromatosis. The circumscribed tumor with a cystic component was located in the medial right temporal lobe. The designation of pleomorphic xanthoastrocytoma has been suggested for this neoplasm on the basis of its unique histological features. These include positive glial fibrillary acidic protein staining. PMID- 8481945 TI - Supratentorial glioblastoma in children: a series of 27 surgically treated cases. PMID- 8481946 TI - Value orientation, health beliefs, and cardiovascular health in young African American women. PMID- 8481947 TI - Development of antigenic heterogeneity in the splenic meshwork of severe combined immunodeficient (SCID) mice after reconstitution with T and B lymphocytes. AB - Recently, we produced monoclonal antibodies reacting specifically with the reticular meshwork (RM) of lymphoid tissues, and demonstrated that, in the splenic white pulp of normal mouse, the antigenic heterogeneity of RM was associated with the segregation of the T and B lymphocytes. In the present study, we attempted to visualize further the interaction between splenic RM and T and B lymphocytes transferred into severe combined immunodeficient (SCID) mice. The splenic white pulp of naive SCID mice, containing a few T and B cells, showed little tendency for T-B segregation and antigenic diversity of RM. Transfer of spleen or bone marrow cells from normal mice resulted in complete recovery of lymphocyte populations, showing not only a clear segregation of T and B lymphocytes but also a remarkable antigenic diversity of RM. The same results were obtained following the transfer of spleen or bone marrow cells from the nude mouse. Next, we transferred purified T lymphocytes to one group of SCID mice and B cells to another. In mice given T cells, a few B cells were observed in the white pulp; T lymphocytes lodged not only in the inner periarterial lymphatic sheath (PALS) but also in the outer PALS and follicles. In the animals to which B cells were transferred, T cells were few and the homing of B cells occurred only into their proper compartments, such as the outer PALS, follicles and marginal zone, but not in the inner PALS. Thus, B cells can home into their proper compartments of the splenic white pulp independently of T lymphocytes. PMID- 8481948 TI - Localization of collagen type VI in articular cartilage of young and adult mice. AB - Collagen type VI was demonstrated immunomorphologically in articular cartilage (distal femur) of young (2-8 weeks) and adult mice by fluorescence and electron microscopy (gold-labelled second antibody--sandwich method) using pre- and post embedding techniques. This collagen type was mainly seen in the vicinity of chondrocytes, and in larger amounts in adult cartilage. Electron-microscopic inspection (pre-embedding technique) revealed labelling above plaques that were 40-160 nm in size, and from which up to 7 fine filaments (< or = 10 nm) per unit sectional plane radiated. Using the post-embedding technique, only labelled plaques could be demonstrated; fine filaments were not perceptible. This was partly a result of the low contrast. It is assumed that the globular ends of up to 20 of the fine type VI filaments are anchored in one plaque and that the antibodies bind to the non-collagenous globular domains. Filaments radiated from the plaques and formed a three-dimensional network that stabilized the structures of the cartilaginous matrix. Antibodies against fibronectin also labelled similar plaques. The ends of the type VI filaments are possibly linked into the plaques by fibronectin. PMID- 8481949 TI - Localization of cholecystokinin-like and calcitonin-like peptides in infant carotid bodies: a light- and electron-microscopic immunohistochemical study. AB - Previous immunohistochemical studies have identified several regulatory peptides in the carotid body chief cells in both humans and animals. These peptides, together with amines, may be important in the modulation of the chemoreflex by the carotid body. We report the localization and distribution of calcitonin and cholecystokinin-like (CCK) immunoreactivity in chief cells of human infant carotid body by light- and electron-microscopic immunohistochemical techniques. Consecutive sections immunostained with calcitonin and/or CCK antibodies revealed positively stained chief cells, both alone and in clusters, scattered throughout the carotid body lobule. Generally more chief cells were positive for calcitonin than for CCK. This was confirmed by quantitative analysis showing that the ratio of calcitonin to CCK immunoreactive cells was consistently > 2:1 in all cases studied. There was no apparent correlation between the immunoreactivity for the two peptides and the age, sex, or postmortem interval. Calcitonin-like and CCK like immunoreactivities were localized electron-microscopically over the dense core granules of the chief cells. Calcitonin and CCK-like peptides in carotid body chief cells may act as neurotransmitters or neuromodulators involved in chemoreception. PMID- 8481950 TI - Localization of neuropeptide Y and atrial natriuretic peptide in the endothelial cells of human umbilical blood vessels. AB - The localization of neuropeptide Y (NPY) and atrial natriuretic peptide (ANP) in the endothelial cells of human umbilical blood vessels was studied using the pre embedding peroxidase-antiperoxidase (PAP) technique for electron microscopy and avidin-biotin-complex (ABC) immunostaining for endothelial cells cultured from umbilical vein. Subpopulations of NPY- and ANP-immunoreactive endothelial cells were present in term umbilical vein and artery. The umbilical vein contained more positive cells than the artery. The percentage of NPY- and ANP-immunoreactive umbilical vein cells in culture was 32% and 44%, respectively, out of a total of 3013 cells examined. The possibility that these potent vasoactive substances located in the endothelial cells of the non-innervated umbilical vessels are involved in the local regulation of blood flow is discussed. PMID- 8481951 TI - Morphology and distribution of Muller cells in the retina of the toad Bufo marinus. AB - We have previously shown that an antibody against neuron-specific enolase (NSE) selectively labels Muller cells (MCs) in the anuran retina (Wilhelm et al. 1992). In the present study the light- and electron-microscopic morphology of MCs and their distribution were described in the retina of the toad, Bufo marinus, using the above antibody. The somata of MCs were located in the proximal part of the inner nuclear layer and were interconnected with each other by their processes. The MCs were uniformly distributed across the retina with an average density of 1500 cells/mm2. Processes of MCs encircled the somata of photoreceptor cells isolating them from each other by glial sheath, except for those of the double cones. Some of the photoreceptor pedicles remained free of glial sheath. Electron microscopic observations confirmed that MC processes provide an extensive scaffolding across the neural retina. At the outer border of the ganglion cell layer these processes formed a non-continuous sheath. The MC processes traversed through the ganglion cell layer and spread beneath it between the neuronal somata and the underlying optic axons. These processes formed a continuous inner limiting membrane separating the optic fibre layer from the vitreous tissue. Neither astrocytic nor oligodendrocytic elements were found in the optic fibre layer. The significance of the uniform MC distribution and the functional implications of the observed pattern of MC scaffolding are discussed. PMID- 8481952 TI - Resident macrophages (ED2- and ED3-positive) do not phagocytose degenerating rat skeletal muscle fibres. AB - Two soleus muscles with degenerating muscle fibres were serially sectioned and adjacent sections from various levels of the skeletal muscles were stained with antibodies that react with either monocytes and inflammatory macrophages (ED1) or with the major subpopulations of resident macrophages (ED2 and ED3). ED2+ and ED3+ resident macrophages were abundant throughout the muscles but were not present within the degenerating fibres. ED1+ cells, in contrast, were rarely observed within the undamaged regions of the muscles but were abundant within the degenerating fibres and in the perimysium between arterioles and degenerating fibres. It is concluded that the phagocytosis of damaged muscle fibres is not carried out by the major subpopulations of resident macrophages. PMID- 8481953 TI - Total numbers of neurons in myenteric ganglia of the guinea-pig small intestine. AB - Two techniques that are thought to stain all of the neurons in the myenteric ganglia of the intestine are NADH diaphorase histochemistry and immunohistochemistry using a "nerve cell body" antiserum. However, this assumption has never been directly verified. In the present study myenteric ganglia of the guinea-pig ileum were prepared as whole-mounts and stained with either of these techniques. All nerve cells that could be identified in the whole mounts were counted. The whole-mounts were then embedded flat in resin and serially sectioned at 1 micron. Nerve cells were identified and counted from the serial sections, and the data compared to those obtained from the whole-mounts. NADH diaphorase histochemistry did not reveal all the neurons at incubation times that gave selective staining. In contrast, "nerve cell body" antiserum stained the entire neuronal population. To determine the total number of nerve cell bodies/ganglion and the proportion of nerve cell bodies with calbindin immunoreactivity, whole-mounts that had been processed for calbindin immunohistochemistry were serially sectioned and reconstructed. The total number of neurons per myenteric ganglion was 105 +/- 10 (SE). Calbindin-immunoreactive neurons comprised about 20% of the myenteric neurons, which is considerably less than previous estimates, because previously the total population has been underestimated. The spatial density of myenteric neurons in the undistended ileum of the guinea-pig is 17,300 nerve cells/cm2. PMID- 8481954 TI - Polarized distribution of gamma interferon-stimulated MHC antigens and transferrin receptors in a clonal cell line isolated from Fisher rat thyroid (FRT cells). AB - The characteristics of a polarized epithelial cell line and dynamics of an endogenous polarized plasma membrane constituent were studied by use of an subclone, FRT-9, from the Fisher rat thyroid cell line, FRT. Transmission electron microscopy (conventional, freeze-fracture), determination of transepithelial electrical parameters and immuno-fluorescence study, were used to establish polarity and demonstrated the basolateral distribution of transferrin receptors and the major histocompatibility complex antigens (constitutive Class I or gamma interferon-induced Class II). PMID- 8481955 TI - Morphofunctional study on prolactin-producing cells of the anterior pituitaries in adult male rats following thyroidectomy, thyroxine treatment and/or thyrotropin-releasing hormone treatment. AB - An immunoelectron-microscopic and morphometric study was carried out on the anterior pituitary prolactin (PRL) cells of adult male Wistar rats treated with a combination of thyroidectomy and administration of L-thyroxine (T4) and/or synthetic thyrotropin-releasing hormone (TRH) in order to clarify the effects of changes in the hypothalamus-pituitary-thyroid axis on the ultrastructure and function of PRL cells. After thyroidectomy, PRL cells underwent atrophy and hypofunction of their cell organelles, but these changes tended to be restored to their normal level by T4 treatment. On the other hand, the administration of TRH to intact rats produced hypertrophy and hyperfunction in the PRL cells, although this treatment had no effect on the PRL cells of thyroidectomized rats. However, treatment with a combination of T4 and TRH had a strong effect and led to hypertrophy and hyperfunction in the PRL cells of thyroidectomized rats. Serum and pituitary PRL levels were measured by radioimmunoassay (RIA) for a comparison with the morphological results. They correlated well with the morphological changes. These results indicate that TRH stimulates PRL secretion in the presence of thyroid hormone, and that the thyroid hormone plays an important role in the basic maintenance of PRL cell function and its reactivity to TRH. PMID- 8481956 TI - Occurrence, distribution and neurochemical features of small intestinal neurons projecting to the cranial mesenteric ganglion in the pig. AB - The small intestine of the pig has been investigated for its topographical distribution of enteric neurons projecting to the cranial mesenteric ganglion, by using Fast Blue or Fluorogold as a retrogradely transported neuronal tracer. Contrary to the situation in small laboratory animals such as rat and guinea-pig, the intestinofugally projecting neurons in the porcine small intestine were not restricted to the myenteric plexus, but were observed in greater numbers in ganglia of the outer submucous plexus. The inner submucous plexus was devoid of labelled neurons. Retrogradely labelled neurons were mostly found, either singly or in small aggregates, in ganglia located within a narrow border on either side of the mesenteric attachment. For both nerve networks, their number increased from duodenum to ileum. All the retrogradely labelled neurons exhibited a multidendritic uniaxonal appearance. Some of them displayed type-III morphology and stained for serotonin. This study indicates that, in the pig, not only the myenteric plexus but also one submucous nerve network is involved in the afferent component of intestino-sympathico-intestinal reflex pathways. The finding that some of the morphologically defined type-III neurons participate in these reflexes is in accord with the earlier proposal that type-III neurons are supposed to fulfill an interneuronal role, whether intra- or extramurally. PMID- 8481957 TI - Ultrastructure of the taste disc in the red-bellied toad Bombina orientalis (Discoglossidae, Salientia). AB - The taste disc of the red-bellied toad Bombina orientalis (Discoglossidae) has been investigated by light and electron microscopy and compared with that of Rana pipiens (Ranidae). Unlike the frog, B. orientalis possesses a disc-shaped tongue that cannot be ejected for capture of prey. The taste discs are located on the top of fungiform papillae. They are smaller than those in Ranidae, and are not surrounded by a ring of ciliated cells. Ultrastructurally, five types of cells can be identified (mucus cells, wing cells, sensory cells, and both Merkel cell like basal cells and undifferentiated basal cells). Mucus cells are the main secretory cells of the taste disc and occupy most of the surface area. Their basal processes do not synapse on nerve fibers. Wing cells have sheet-like apical processes and envelop the mucus cells. They contain lysosomes and multivesicular bodies. Two types of sensory cells reach the surface of the taste disc; apically, they are distinguished by either a brush-like arrangement of microvilli or a rod like protrusion. They are invaginated into lateral folds of mucus cells and wing cells. In contrast to the situation in R. pipiens, sensory cells of B. orientalis do not contain dark secretory granules in the perinuclear region. Synaptic connections occur between sensory cells (presynaptic sites) and nerve fibers. Merkel cell-like basal cells do not synapse onto sensory cells, but synapse-like connections exist between Merkel cell-like basal cells (presynaptic site) and nerve fibers. PMID- 8481958 TI - Effect of omeprazole-evoked hypergastrinemia on ultrastructure of enterochromaffin-like cells in the stomach of portacaval-shunted rats. AB - The histamine-producing enterochromaffin-like (ECL) cells in the acid-producing portion of the rat stomach responded to long-standing hypergastrinemia (omeprazole treatment daily for 8-10 weeks) with hypertrophy (and hyperplasia) and with a reduced number of granules and vesicles per unit cytoplasm. There was a reduction in the ratio of electron-dense granules versus vesicles and an increase in the profile diameter of the vesicles. Also, portacaval shunting (PCS) induced changes in the ECL cells, manifesting (i) as an increase in cell number and size, and (ii) as a reduced number of granules and vesicles per unit area. The cytoplasmic granules and vesicle profiles were enlarged, and the ratio of granules versus vesicles was reduced. The combination of PCS and long-standing hypergastrinemia (omeprazole treatment) produced a greatly enhanced ECL cell hypertrophy (and hyperplasia) and a marked reduction in the number of granules. The ratio of granules versus vesicles was markedly reduced while the profile diameters of both granules and vesicles were increased. The relative predominance of very large vesicles (vacuoles) was a prominent feature of the ECL cells in these rats. PMID- 8481959 TI - Topography of short portal vessels in the rat pituitary gland: a scanning electron-microscopic and morphometric study of corrosion cast replicas. AB - We applied scanning electron microscopy combined with imaging and morphometric techniques to analyze the dorsal topography and morphology of short portal vessels linking the capillary beds of the pituitary neural and anterior lobes in adult male albino rats. The pituitary microvasculature was replicated by intracarotid injection of Batson's No. 17 compound producing plastic casts that were advantageous for comprehensive morphometric analyses using an imaging device. The analysis revealed the existence of two types of portal vessels having quantitatively different morphological properties. The bilateral venular plexus of 3-4 vessels located at the base of the infundibular stalk (each venule measuring 300 microns in length and 32 microns in diameter) appears to be the major part of the short portal system in the dorsum of the rat pituitary gland. Narrower capillary-like shunt vessels (6.8 microns in diameter), of about the same length as the venules, were situated throughout other subregions of the intermediate lobe cleft. The short portal vessels of both types made direct anastomoses with the capillary networks in the neural and anterior lobes. The neural lobe capillaries were twice as numerous (1324 per mm2), and only half as wide (6.2 microns), as the sinusoidal capillaries in the anterior lobe (density of 637 per mm2; diameter of 13.7 microns). The topographical position of the portal venular system suggests that the caudolateral subregions of the pituitary neural and anterior lobes have a functional relationship dependent on rapid interlobe transfer of neurohumoral factors such as hormones via the portal blood. This process appears to be supplemented throughout the rest of the cleft between the two lobes by a small number of capillary shunts that supply the epithelial cell lobules of the intermediate lobe in situ. The findings collectively indicate that this portal system provides a constant stream of neurohumoral information that is shared moment-by-moment between the pituitary neural and anterior lobes. PMID- 8481961 TI - Year-round conditioning for basketball. AB - Year-round conditioning specifically designed for basketball has reached a high level of sophistication over the past several decades. There is growing evidence that it can contribute to improved performance and reduced injury. The major components of conditioning for basketball have been identified as anaerobic power (stages I and II), aerobic power, muscular strength/power/endurance, and flexibility. The concept of year-round conditioning uses the principles of periodization in work and rest to achieve peak performance and avoid injury. There are unique problems associated with the various levels of competition that require diligent monitoring on the part of the coach to maximize physical condition and avoid overtraining. PMID- 8481960 TI - Catalase-negative peroxisomes in human embryonic liver. AB - Hepatic peroxisomes in human embryos with a menstrual age of 6 and 7 weeks have been examined via catalase cytochemistry. In the younger sample, the organelles show no catalase activity, their matrix being pale and coarsely reticular. In the 7-week specimen, the peroxisome population consists of catalase-positive and catalase-negative organelles. The latter have a morphology identical to that of the 6-week sample and represent 66% of the population. The positive organelles show a pronounced staining heterogeneity. Together with the simultaneous presence of negative organelles, this might reflect the onset of catalase import into the peroxisomes during this period. Catalase heterogeneity excludes a continuous exchange of matrix contents; moreover, interconnections between peroxisomes have not been observed, and no cluster formation occurs. The data therefore also suggest that catalase is imported into individual, preexisting organelles in embryonic liver. The three peroxisomal beta-oxidation enzymes become detectable by immunocytochemistry only later during development. Morphological indications for a rapidly dividing population, such as elongated and/or tailed organelles, have not been observed. Morphometry has revealed that, in these early stages, the organelles are significantly smaller than the peroxisomes of fetal and adult human liver. PMID- 8481962 TI - A protocol for the health and fitness assessment of NBA players. AB - The assessment of the health and fitness of elite basketball players should be a multidisciplinary process. We have described an organized, efficient, and comprehensive protocol for preseason physical evaluations that could be used at the university as well as professional level. PMID- 8481963 TI - Assessment and treatment of basketball injuries. AB - In this article, we have discussed acute musculoskeletal injuries, acute exacerbations of illness related to basketball, and preparation for these emergencies. Although the acute nature of the problems require constant diligence on the part of the health care provider, the rewards of good management to the player and to the treating physician make it all worthwhile. PMID- 8481964 TI - Special considerations in the medical management of professional basketball players. AB - The NBA basketball players are among the finest athletes in the world. That along with the increased popularity of the NBA has put a premium on the health of the players. The course of the season puts tremendous stress and strain on players. As medical illnesses occur, the physician may feel increased pressure to put the ill player back into the line-up. One cannot let the pressure for the player to return to activity interfere with good medical practice. At times, it is difficult to allow for the natural course of an illness, however, as discussed in this article, sometimes this is exactly what needs to be done. The temptation to overtreat is also seen in some team physicians. This too must be avoided. Along with proper treatment, there is the need for education of the athletes both in social interactions and in diet and life-style. Then we, as team physicians, can sit back and enjoy the performance on the court. PMID- 8481965 TI - Common hand and wrist injuries in basketball players. AB - Multiple injuries to the hand are relatively common in basketball. This article explains the importance of an early and thorough examination, preferably by a hand specialist. It is important to obtain a history of prior injury during the assessment because treatment and prognosis may be very different. Delayed treatment often yields an inferior result and lost time. If an injury is not treated initially, it may require operative treatment or even be untreatable. PMID- 8481966 TI - Back injuries in basketball players. AB - The basketball player with lower back or lower extremity radicular pain needs to be carefully evaluated. A complete history of any previous symptomatology and a specific history of the new injury are absolutely essential. A careful physical examination with an understanding of the anatomy as well as possible causes of the lower back pain is crucial. An accurate diagnosis is essential in treating every athlete. Most basketball-related lower back injuries will respond to conservative nonsurgical treatment. Rehabilitation is a cornerstone in not only treating the initial symptoms, but decreasing the risks of reinjury. The goal of returning the basketball player to previous performance level as quickly as possible, with a minimal risk of re-injury, is the goal of the team physicians. PMID- 8481967 TI - Injuries of the posterior cruciate ligament. AB - A review of the anatomy and biomechanics of the posterior cruciate ligament, and the systematic approach for the diagnosis and treatment of isolated posterior cruciate ligament injuries and posterior cruciate ligament insufficiency in combination with other ligamentous instabilities is discussed. PMID- 8481968 TI - Basketball knee injuries and the anterior cruciate ligament. AB - Basketball arguably may present the greatest risk for anterior cruciate ligament (ACL) injury because it is well known that ACL injuries may occur with external or internal rotation of the tibia with or without hyperextension. All of these mechanical phenomena occur repetitively in a running, jumping, and cutting sport such as basketball. This article discusses the diagnosis and mechanism of injury as well as treatment of ACL injury. PMID- 8481969 TI - Rehabilitation of anterior cruciate ligament injuries. AB - Rehabilitation of the anterior cruciate ligament absent or reconstructed knee is becoming a true artform. Accelerated, but controlled rehabilitation, is becoming more commonplace. Scientific-based data along with clinical experiences are the basis of the rehabilitation guidelines brought forth in this article. Anterior cruciate ligament strain and implications for exercise, continuous passive motion, proprioceptive exercise, and the role of knee bracing are all discussed in relation to the overall rehabilitation program. PMID- 8481970 TI - Overuse injuries of the knee in basketball. AB - Overuse injuries of the knee are abundant in basketball players. This article discusses the pathophysiology of overuse and the principles of treatment. The diagnosis and clinical management of jumper's knee, patellofemoral pain, and stress fractures are outlined with specific attention to rehabilitation techniques and training. PMID- 8481971 TI - Sprained ankles as they relate to the basketball player. AB - Concepts based on newer medical information concerning ankle injuries have changed in recent years. With these changing concepts, the method of treatment has also changed. It is the purpose of this article to review some of the commonly known information concerning ankle sprains, to emphasize the association of subtalar injury with the ankle sprain complex, to outline new information concerning the static stabilizers on the lateral aspect of the ankle, and finally, to utilize this information in producing a rationale for a new type of surgical treatment for chronic instability of the ankle. PMID- 8481972 TI - Pretreatment with glucose infusion prevents fatal outcome after hemorrhage in food deprived rats. AB - Twenty-four hour food deprivation increases mortality after experimental hemorrhage. Survival after hemorrhage is closely related to the capacity of the animal to develop hyperglycemia. In this study, 24 hr food deprived rats were given a 3-hr infusion of either 0.3 ml/100 g b.wt./h 30% glucose iv (n = 10) or the same volume of 0.9% NaCl (n = 10) prior to 60 min of standardized hemorrhage. Glucose infusion resulted in a transient hyperglycemia, and 600% greater hepatic glycogen content compared to saline (P < 0.001). During hemorrhage, glucose treated rats developed substantial hyperglycemia while glucose levels fell in saline treated (P < 0.001). Concomitant developments in hematocrits indicated improved plasma refill in glucose treated animals (P < 0.01). While saline treated rats developed irreversible shock and died within 3 hr of bleeding, glucose treated rats had a MAP of 52 +/- 2 (mean +/- SEM) mm Hg by the end of hemorrhage (P < 0.01). All glucose-treated rats recovered and survived the seven day observation period. It is concluded that glucose infusion leading to hepatic glycogen repletion alters outcome after experimental hemorrhage in food deprived animals. These experimental results may be of clinical relevance, since elective surgery is generally performed after overnight fasting, which substantially reduces the hepatic glycogen reserve. PMID- 8481973 TI - Endothelin-1-induced increases in microvascular permeability in isolated, perfused rat lungs requires leukocytes and plasma. AB - Effect of endothelin-1 (ET-1) (10(-8) M) on pulmonary microvascular permeability was examined in isolated rat lungs perfused with blood or various blood components. Microvascular permeability was assessed by measuring fluid filtration rate (FFR) in lungs pretreated with papaverine in order to prevent changes in vascular smooth muscle tone. ET-1 significantly increased FFR (131.0 +/- 10.1 mg/min, P < 0.01) after perfusion with blood for 60 min. In lungs perfused with leukocytes resuspended in plasma, ET-1 increased FFR significantly both 30 min (40.4 +/- 11.4 mg/min, P < 0.01) and 60 min (97.4 +/- 14.5 mg/min, P < 0.01) after it was added to the perfusate. Heat inactivation (56 degrees C; 1 hr) of plasma did not attenuate this effect of ET-1 (94.4 +/- 25.1 mg/min, P < 0.01). When lungs were perfused with leukocytes resuspended in Krebs Ringer albumin instead of plasma, or with plasma only, ET-1 did not cause any change in FFR. In conclusion, ET-1 increases microvascular permeability in isolated blood-perfused rat lungs. The effect is critically dependent on the presence of leukocytes and plasma components other than complement. PMID- 8481974 TI - Effectiveness of dual cyclooxygense and leukotriene blockade with ibuprofen and LY203647 during canine endotoxic shock. AB - Ibuprofen and the leukotriene antagonist, LY203647, were used to evaluate the effectiveness of LY203647 in the dual blockade of cyclooxygenase and leukotriene to maintain hemodynamic parameters in endotoxemia. Ibuprofen pretreatment alone or dual blockade (ibuprofen plus LY203647) protected blood pressure and renal blood flow at 1 and 3 hr after endotoxin infusion. Cardiac output at 1 hr after endotoxin in dogs treated with ibuprofen was slightly but significantly decreased. Dual pretreatment prevented this decrease at 1 hr; however, cardiac output was similar in both groups by 3 hr. Dual blockade administered after endotoxin induced increases in blood pressure and cardiac output at 3 hr. LY203647 pretreatment alone did not prevent the postendotoxemic declines in any measured parameters. The increased plasma SGOT and lactate of endotoxemia were exacerbated by LY203647 and blunted by ibuprofen treatment. We conclude that the addition of LY203647 to ibuprofen treatment offers no additional significant protection of hemodynamic parameters. PMID- 8481975 TI - Pentoxifylline does not prevent endotoxin induced lung and liver lipid peroxidation in the adult sheep. AB - Our purpose was to determine the effect of pentoxifylline pretreatment on endotoxin-induced (5 microgram/kg) lung and systemic oxidant activity, measured as lipid peroxidation. We used the awake adult sheep with lung and soft tissue lymph fistulae to monitor microvascular changes as well as to monitor oxygen delivery and consumption. Oxidant activity was monitored using the level of plasma conjugated dienes, a measure of circulating lipid peroxides, and lung and liver malondialdehyde content, a measure of tissue lipid peroxidation. Sixteen sheep were given endotoxin, eight of which were pretreated with pentoxifylline (20 mg/kg bolus) followed by a 6 mg/kg/hr infusion. We found that the degree of early endotoxin-induced pulmonary hypertension and hypoxia and later increased pulmonary microvascular permeability was not attenuated with pentoxifylline. In addition, a comparable increase in circulating conjugated dienes, lung neutrophil sequestration, and a three-fold increase in lung malondialdehyde was seen in both groups. Soft tissue QL also increased to the same degree in both groups. Liver MDA increased from a control of 110 +/- 20 nM/g tissue to 165 +/- 32 nM/g with endotoxin alone and to 260 +/- 55 nM/g with pentoxifylline pretreatment, a significant increase over both control and endotoxin alone groups. Pentoxifylline, however, did improve hemodynamic stability, required significantly less fluid, and prevented the hyperdynamic state seen at 4-5 hr post endotoxin. We conclude that pentoxifylline attenuates the initial endotoxin induced hemodynamic instability, and later hyperdynamic state. However, pentoxifylline pretreatment does not appear to prevent endotoxin-induced oxygen radical release in the unanesthetized sheep. PMID- 8481976 TI - Removal of the submandibular glands increases the acute hypotensive response to endotoxin. AB - We investigated the roles of the submandibular glands and of their sympathetic innervation on the acute hypotensive response induced by the i.v. injection of endotoxin (10 mg/kg; Salmonella typhosa) into rats anesthetized with sodium pentobarbital. Endotoxin given to unoperated and sham-operated rats induced a transient 30-40 mm Hg drop in blood pressure. Rats that had their submandibular glands removed (sialadenectomy) or bilateral resection of the superior cervical ganglia (ganglionectomy), exhibited significantly larger drops in blood pressure (approximately 65 mm Hg) that were maintained for the 60 min of the experiment. This increased responsiveness to endotoxin in sialadenectomized and ganglionectomized animals was not related to changes in haematocrit, white blood cell counts, or neutrophil activity. Pretreatment of rats with pentoxifylline (PTX) produced substantial protection against the hypotensive effects of endotoxin in ganglionectomized and sialadenectomized rats, although this xanthine did not affect the responses of sham-operated rats. These results suggest that the submandibular gland elaborates a factor that protects against acute hypotension induced by endotoxin and that this factor is under the control of the cervical sympathetic nervous system. PMID- 8481977 TI - Triiodothyronine (T3) improves cardiovascular function during hemorrhagic shock. AB - Prior work showed that an intact thyroid axis augments survival from hemorrhagic shock (HS); this study assesses the effects of specific thyroid-related hormones on cardiovascular (CV) function during HS. Following thyroidectomy, 32 conditioned male dogs were subjected to HS to a mean arterial pressure (MAP) of 60 mm Hg for 90 min then to 40 mm Hg for 30 min. Postshock (PS), the dogs received thyroid-releasing hormone (TRH; 2 mg/kg), thyroid-stimulating hormone [control (TSH; 10 IU)], T3 (12 micrograms/kg), or T4 (40 micrograms/kg). Thirty minutes following treatment (PTX), they were resuscitated with shed blood and 50 ml/kg saline. CV and hormonal parameters were measured PS, PTX, postresuscitation (PR), and on day 2 (D2). There were no PS differences in CV parameters between groups. Following treatment, T3 significantly increased MAP (59.0 +/- 13 vs, 39.9 +/- 2.2 mm Hg) and cardiac output (CO; 0.92 +/- 0.1 vs. 0.80 +/- 0.1 liter/min; P < 0.05 by ANOVA). TRH treatment significantly improved PTX MAP (62.7 +/- 10 vs. 40.8 +/- 2.1; P < 0.05 by ANOVA). TSH and T4 did not significantly change PTX MAP or CO. There were no significant CV differences in the four groups following resuscitation or on D2. In conclusion, T3 improves MAP and CO during hemorrhagic shock. TRH transiently improved PTX blood pressure. Further study of the mechanism of this beneficial response afforded by T3 administration is warranted. PMID- 8481978 TI - Hemodynamic responses to changes in carotid sinus pressure after endotoxin and ibuprofen. AB - The hemodynamic responses to changes in carotid sinus pressure (CSP) were evaluated in nine pentobarbital-anesthetized dogs during control, endotoxin treatment, and ibuprofen (after endotoxin) treatment periods. Both carotid sinuses were isolated and perfused at varying pressures with oxygenated blood in the vagotomized animal. Alterations in carotid sinus pressure and the resultant responses were measured at 15-min intervals during a 30-min control period, for 60 min after 1 mg/kg endotoxin, and for 60 min after 10 mg/kg ibuprofen given after endotoxin. The results showed a reduction in calculated gain for mean arterial pressure (MAP) (change in arterial pressure/change in CSP), heart rate, and peripheral resistance (TPR) after endotoxin, without a corresponding reduction in cardiac output (CO) gain. These gain changes were accompanied by a decrease in absolute MAP, CO, and TPR. An indicator for cardiac performance gain also increased. Relatively, arterial pressure was partially maintained by an increase in CO despite a loss in ability to vasoconstrict. Ibuprofen failed to correct the MAP gain, and only partially restored MAP, but shifted a greater relative response to peripheral resistance. To test if TPR would also decrease if the decrease in CO was prevented, three additional animals were studied with a pump in series with the heart to maintain CO; TPR again dropped after endotoxin. The results indicate a loss of peripheral arterial tone after endotoxin, partially restored by ibuprofen. The CO response indicates a peripheral vascular failure rather than a central or carotid sinus failure mechanism. PMID- 8481979 TI - Adrenergic blockade attenuates endotoxin-induced hepatic glucose uptake. AB - The purpose of the present study was to elucidate the role of catecholamines in mediating the endotoxin-induced increase in glucose uptake of individual tissues. In vivo glucose utilization by selected tissues, assessed by the 2-deoxyglucose (2dGlc) tracer technique, was determined 3 hr following the i.v. injection of Escherichia coli lipopolysaccharide (LPS; 100 micrograms/100 g bw) or saline. Catecholamine action was inhibited by the combined administration of alpha and beta receptor antagonists, phentolamine and propranolol. Adrenergic antagonists alone did not change plasma glucose levels or the glucose metabolic rate (Rg) of the investigated tissues; however, adrenergic blockage resulted in mild hypoglycemia in endotoxemic animals. LPS administration increased in vivo Rg by the liver (571%), lung (229%), spleen (210%), intestine (76%), skin (82%), fat (181%), gastrocnemius muscle (70%), and kidney (61%). There was a significant elevation in the glucose metabolic clearance rate (MCR) by these tissues as well. LPS did not increase Rg by brain and testis. Adrenergic blockade completely prevented the LPS-induced Rg increase in the liver and partially inhibited the elevation in other tissues. The LPS-induced increase in the MCR in spleen, lung, intestine, skin, fat, muscle, and kidney was not altered by adrenergic blockade, indicating that the attenuated Rg in these tissues was the consequence of the decreased plasma glucose concentration observed under this condition. However, in the liver, adrenergic antagonists markedly inhibited the LPS-induced increase in both Rg and MCR. Thus our data indicate that the glucose metabolic response to LPS is partially mediated by catecholamines through the accompanying changes in plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481980 TI - Endotoxin contamination of superoxide dismutase and catalase. PMID- 8481981 TI - Does smoking influence acne? AB - One hundred and sixty-five patients with acne completed a questionnaire on smoking habits. Amongst 96 males, 19.7% were smokers (95% confidence interval 12.4-29.2%) compared to an expected prevalence of 34.5% from national statistics (P < 0.001). For 69 females, a prevalence of 12.1% (95% confidence interval 6.1 23.3%) was obtained compared to 32.7% expected (P < 0.001). The findings of this study support the hypothesis that some component of cigarette smoke, possibly nicotine, has an anti-inflammatory action on acne. PMID- 8481982 TI - Levels of fluconazole in serum, stratum corneum, epidermis-dermis (without stratum corneum) and eccrine sweat. AB - The distribution in the skin of orally active antifungals and other drugs claimed to be active in the treatment of skin diseases is of major importance, but to date has been studied only rarely. In the present study the distribution of fluconazole in stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat and serum was studied in human male volunteers after dosages of 50 mg daily for 12 days and 150 mg once weekly for 2 weeks. In the present study high levels of fluconazole were found especially in the stratum corneum. At a dose of 50 mg once daily the concentration of fluconazole after 12 days was 73.0 micrograms/g and 7 days after cessation of treatment the concentration was still 5.8 micrograms/g. At the 150 mg once a week dose the concentration 7 days after the second dose was still 7.1 micrograms/g in stratum corneum indicating that medication once a week may be effective in the treatment of dermatomycoses. High concentrations, all above the serum concentrations, were also seen in sweat and epidermis/dermis. These results indicate that fluconazole is delivered to the stratum corneum, where it is accumulated, through sweat and by direct diffusion through the dermis-epidermis. These pharmacokinetic results indicate that the drug should be very effective in the treatment of dermatomycoses. An extremely high concentration of the drug in the stratum corneum combined with concentrations from 2.93 to 4.62 micrograms/g in the rest of the epidermis and dermis is important in the treatment of these diseases. PMID- 8481983 TI - Improvement in survival rate of patients with acral melanoma observed in the past 22 years in Sendai, Japan. AB - While the incidence of malignant melanoma is much lower in Japanese than in Caucasians, the commonest site of melanoma in Japanese has been reported to be the acral regions of the limbs. The survival rate for acral and nodular melanoma observed at the Department of Dermatology, Tohoku University Hospital in Sendai, Japan from 1969 to 1990 was reviewed. Among 150 melanoma patients 125 (83%) and 17 (11%) had primary cutaneous melanoma and mucous membrane melanomas, respectively. Frequent sites for cutaneous melanomas were the sole (31%) and subungual regions (15%). Comparison of the stages of plantar melanoma at diagnosis showed that the proportion of stages III and IV decreased after 1980 with a corresponding increase in those with a tumour thickness of less than 4 mm (stage II). Concurrently, the prognosis of plantar melanoma has improved; the 5 year survival rate in each of the three periods 1969-75, 1976-80 and 1981-85 was 21, 70 and 90%, respectively. This was also the case with subungual melanoma. Such improvements in the prognosis are thought to be mainly due to early detection through the growing public awareness of this life-threatening disease. By contrast cases of nodular melanoma increased sharply after 1980. Among these, the high proportion of patients in advanced stages (stages III and IV) remained static even after 1980, with a resultant low 5-year survival rate in the above mentioned periods of 33, 38 and 18%, respectively. PMID- 8481984 TI - Histoanalytical study of the cellular infiltrate in the tuberculin reaction. AB - In contrast to the generally held view, in previous studies it has been found that the histopathological changes in delayed-type hypersensitivity reactions to intradermal purified protein derivative of tuberculin (PPD) in humans were not uniform. These were classified into three types based on their resemblance to features seen in other dermatoses, i.e.: (i) perivascular dermatitis type; (ii) basal spongiotic dermatitis type; and (iii) erythema multiforme type. These histopathological patterns correlated well with the clinical response seen in tuberculin hypersensitivity of tested subjects. In the present study, the immunohistopathological features in 44 skin biopsy specimens were assessed quantitatively by using multivariate analysis. The numbers of infiltrating cells in the epidermis and in the dermis which were immunohistologically positive to monoclonal antibodies against various mononuclear cells were counted separately to determine if there was any statistical correlation between the histopathological patterns and the phenotypes of infiltrating cells. As a result, a significant correlation was found between the histopathological patterns and the phenotypes of cells infiltrating the epidermis, such as CD8+ cells, CD4+ cells, CD11c+ cells and interleukin 2 receptor positive cells. All these cells showed a high correlation coefficient to the expression of HLA-DR antigen by keratinocytes. Next, factors that might regulate the inflammation and interaction among the infiltrating cells were assessed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8481985 TI - An immunohistochemical study of the distribution of plasminogen and plasminogen activators in bullous pemphigoid. AB - Abnormalities of the cutaneous plasminogen/plasminogen activator system have been associated with acantholytic disorders, psoriasis, keratinocytes in culture, and epidermis in healing wounds. The present study was undertaken to investigate the possible role of the plasmin/plasminogen protease system in lesion development in bullous pemphigoid (BP). Using polyclonal antibodies and a fluorescent technique, the immunohistochemical distribution of plasmin/plasminogen, fibrinogen and the plasminogen activators, urokinase (uPA) and tissue plasminogen activator (tPA), were studied in lesional and non-lesional skin from nine BP patients, one with linear IgA disease (LAD) and one with pemphigoid gestationis (PG). The distribution of the proteases was compared with that in normal skin (n = 4) and in suction blisters (n = 2). In normal skin, fibrinogen, tPA and uPA were absent from the epidermis and plasminogen was confined to the basal layer. Uninvolved BP skin was identical to controls. Focal areas of suprabasal plasminogen expression in the region of a blister was seen in 3/9 BP lesions and in 1/2 suction blisters. In 6/9 BP lesions and both uninvolved and lesional LAD and PG skin were identical to controls, and no suprabasal expression of plasminogen was present. These findings suggest that suprabasal plasminogen expression is unlikely to play a fundamental role in the pathogenesis of blister formation in BP as enhanced expression was not present in every case and the finding was not specific to BP, also occurring in a suction blister. Enhanced plasminogen expression rather may be a reflection of the processes of tissue repair. PMID- 8481986 TI - Laser therapy of verrucous epidermal naevi. AB - Forty-three patients with verrucous epidermal naevi were treated either with argon-laser coagulation or with carbon-dioxide laser vaporization. With the argon laser, very good to acceptable results could be achieved in 85% of patients with 'soft', papillomatous lesions. In 'hard', keratotic naevi the argon laser proved ineffective. In some of these cases CO2-laser treatment was effective, whereas generally there was a tendency to hypertrophic scar formation with this laser. As other therapeutic modalities for epidermal naevi are either insufficient or not applicable in widespread lesions, we feel that laser treatment is a valuable therapeutic alternative. PMID- 8481987 TI - Clinical utility of fluorometric scanning of plasma porphyrins for the diagnosis and typing of porphyrias. AB - The fluorometric emission scanning (using excitation at 405 nm) of plasma samples, simply diluted five-fold in phosphate-buffered saline, allows the differentiation of three conditions according to their porphyrin content. The emission maximum at 626-628 nm is a specific finding in variegate porphyria, while in erythropoietic protoporphyria a characteristic peak is found at 636 nm. A fluorescence emission maximum at 618-622 nm corresponds to a third group that includes normal subjects, non-porphyria patients and patients suffering from acute intermittent porphyria, hereditary coproporphyria, congenital erythropoietic porphyria (Gunther disease) and porphyria cutanea tarda. Therefore, this simple, quick and cheap screening test allows one to establish whether a patient with a photocutaneous syndrome has porphyria and whether this porphyria belongs to the types: variegate, protoporphyria or other cutaneous porphyrias. PMID- 8481988 TI - Bacillary epithelioid angiomatosis in acquired immunodeficiency syndrome (AIDS)- clinicopathological and ultrastructural study of a case with a review of the literature. AB - Bacillary epithelioid angiomatosis (BEA) is a rare cutaneous disorder usually affecting patients with human immunodeficiency virus (HIV) infection often misdiagnosed as a vascular tumour. We describe a 51-year-old, HIV-positive, Caucasian, homosexual male who developed scattered papulo-nodular lesions with clinicopathological and ultrastructural features of BEA. He had a dramatic therapeutic response to systemic antibiotics. There has been a lack of such reports in the European literature. The differential diagnosis is discussed and a brief review of the English literature to date is included. PMID- 8481989 TI - Heparin skin necrosis--an important indicator of potentially fatal heparin hypersensitivity. AB - Skin necrosis at injection sites is a rare complication of heparin therapy. In this report, we describe only the second case of the even rarer complication of skin necrosis occurring at sites distant to those of subcutaneous heparin injections. The patient had also suffered systemic thrombotic events due to heparin-dependent platelet activation prior to the development of the skin necrosis, although these had not been recognized as such at the time. The development of heparin-induced skin necrosis should result in the immediate cessation of heparin therapy in order to prevent potentially fatal thrombotic events. This is in contrast to warfarin-induced skin necrosis, where therapy may be continued or restarted at a lower dose. PMID- 8481990 TI - Familial Jessner's lymphocytic infiltration of the skin, occurring in a father and daughter. AB - Familial occurrence of Jessner's lymphocytic infiltration of the skin is reported in a father and daughter. A definitive diagnosis of Jessner's disease was greatly facilitated by the presence of large numbers of plasmacytoid monocytes within the dermal infiltrates in both patients. A role for skin-directed lymphocyte migration is suggested to account for the presence of this peculiar cell type. PMID- 8481991 TI - Localized pachydermodactyly in tuberous sclerosis. AB - Pachydermodactyly refers to a rare form of digital fibromatosis involving the proximal portions of the fingers. There are only nine cases reported in the literature, all idiopathic and occurring in young men. We report a 5-year-old Chinese boy with tuberous sclerosis who presented with localized pachydermodactyly since birth. This congenital form of pachydermodactyly may represent an additional cutaneous sign of tuberous sclerosis. PMID- 8481992 TI - Acne induced by inhaled corticosteroids. AB - Four cases of acne apparently induced by inhalation of potent corticosteroids prescribed for the treatment of asthma are described. In one case there appeared to be a dose-dependent relationship. While acne induced by topical or systemic administration of corticosteroids is well recognized, acne following inhaled corticosteroids has not previously been reported. PMID- 8481993 TI - Systemic nodular panniculitis in a patient with alpha-1 antitrypsin deficiency (PiSS phenotype). AB - The association of alpha-1 antitrypsin deficiency (PiZ phenotype) with systemic nodular panniculitis has been well documented. Despite reports of cases of systemic nodular panniculitis associated with other alpha-1 antitrypsin deficiency phenotypes, it is still not known if this association is fortuitous rather than causal. We report a case of systemic nodular panniculitis associated with alpha-1 antitrypsin deficiency (PiSS phenotype), with clinico-pathological features similar to those reported in cases associated with the PiZ phenotype. PMID- 8481994 TI - Cutaneous phaeohyphomycosis due to Alternaria alternata responding to itraconazole. AB - An 81-year-old man presented with a spreading, eczematous-appearing rash on the dorsum of the right hand and forearm, originating from three small, probably post traumatic, ulcers over the knuckles. He had the nephrotic syndrome for which he was on 60 mg prednisone daily. Histology of a biopsy of lesional skin was consistent with phaeohyphomycosis and Alternaria alternata was cultured. The rash cleared following treatment with 100 mg itraconazole daily and tapering of his prednisone dose. PMID- 8481995 TI - Livedo reticularis in a patient with systemic lupus erythematosus and anticardiolipin antibodies. AB - This report describes a case of livedo reticularis associated with increased titres of anticardiolipin antibodies (aCL) in a patient with systemic lupus erythematosus. A 38-year-old woman presented with fever, malaise, arthritis and livedo reticularis in a severe form. Antibodies to native DNA and an increased level of aCL were found. A significant positive correlation exists between livedo reticularis and elevated serum antiphospholipid activity in patients with systemic lupus erythematosus. aCL are shown to play a possible pathogenetic role in thrombotic events. This suggests that thrombosis is the underlying cause of livedo in these patients. A biopsy performed in a patient at the site where livedo was most marked showed no evidence of thrombi. It is postulated that the mechanism of livedo in lupus patients with aCL consists of both thrombosis and dysfunction in the regulation of the tone of the peripheral vascular bed. PMID- 8481996 TI - Hairy pigmented congenital naevocellular naevus in a patient with alopecia universalis. PMID- 8481997 TI - Acute lipodermatosclerosis in a pendulous abdomen. AB - A 54-year-old female developed tender, hot, erythematous skin at the apex of a large pendulous abdomen at the same time as she became symptomatic with congestive cardiac failure secondary to respiratory failure. Clinically and histologically the changes in the abdominal-wall skin resembled lipodermatosclerosis, a condition normally seen in the legs secondary to chronic venous insufficiency. PMID- 8481998 TI - Erythrodermic psoriasis. Report of a case associated with symptomatic hypophosphataemia. AB - We describe a patient with a long history of psoriasis who developed severe erythrodermic psoriasis associated with lethargy, muscular weakness and collapse. Serum biochemical screening at the time revealed severe hypophosphataemia, and when this was corrected by intravenous phosphate replacement her symptoms resolved and her psoriasis improved. Hypophosphataemia may therefore be another metabolic complication of erythrodermic psoriasis. PMID- 8481999 TI - Erosive, flexural lichen planus--an uncommon variant. AB - An unusual pattern and type of lichen planus is described in a 57-year-old female in which the flexures were exclusively involved. The affected areas were chronically eroded and ulcerated and resistant to topical treatment. Erosive lichen planus is known to occur on mucosal surfaces and cases of ulcerative lichen planus have been described involving the feet and lower limbs. Lichen planus involving flexures alone is uncommon and for erosion and ulceration to occur at these sites seems rare. We report a case of erosive, flexural lichen planus of long standing in a middle-aged female. PMID- 8482000 TI - Improvement of trigeminal neurotrophic ulceration with pimozide in a cognitively impaired elderly woman--a case report. AB - Neurotrophic ulceration of the face is a rare but well recognized sequel to division of the trigeminal nerve. Trauma is an important contributory factor and thought to be due in part to paraesthesiae, which encourages picking and scratching, with resultant chronic and persistent ulceration. A case is described of an 82-year-old woman with severe trigeminal neurotrophic ulceration which improved substantially with pimozide, given for treatment of unrelated paranoid symptoms. The possible relevance of this to the established use of pimozide in delusional parasitosis is briefly discussed. PMID- 8482001 TI - Angiosarcoma in congenital hereditary lymphoedema (Milroy's disease)--diagnostic beacons and a review of the literature. AB - In cases of congenital lymphoedema the finding of ulceration, violaceous nodules or papules, or apparent traumatic ecchymoses should act as a diagnostic beacon warning of dangers. A case is reported of a high-grade angiosarcoma developing in a patient with congenital hereditary lymphoedema (Milroy's disease). This is the second paper to report this complication, the third case report and the first case in which the diagnosis is substantiated by immunohistochemistry and lectin histochemistry. A review of cases of angiosarcoma complicating congenital hereditary and non-hereditary lymphoedema is also presented. PMID- 8482002 TI - Abstracts from the Joint Meeting of the Society for Cutaneous Ultrastructure Research (18th annual meeting) and the Japanese Society for Ultrastructural Cutaneous Biology. Vienna, 23-25 May 1991. PMID- 8482003 TI - The treatment of herpes zoster with flamazine--a double-blind placebo-controlled trial. PMID- 8482004 TI - Subepidermal bullous eruption induced by captopril. PMID- 8482005 TI - Lack of reactivity of glutenin and gliadin antisera to normal and dermatitis herpetiformis skin. PMID- 8482006 TI - Scabies keloid. PMID- 8482007 TI - Pustular psoriasis in childhood. AB - Recurrent annular pustular psoriasis over the trunk of an 11-year-old boy followed infantile psoriasis in the napkin area. Etretinate therapy induced a partial remission. The difficulty in distinguishing between annular pustular psoriasis and subcorneal pustular dermatosis of Sneddon and Wilkinson is discussed. PMID- 8482008 TI - Heat shock gene expression and development. I. An overview of fungal, plant, and poikilothermic animal developmental systems. PMID- 8482009 TI - The independent stage-specific expression of the 18-kDa heat shock protein genes during microsporogenesis in Zea mays L. AB - The small (18-kDa) heat shock proteins (hsps) of maize are encoded by a complex multigene family. In a previous report, we described the genetic information from cDNAs encoding two different members of the family. In this communication, we report the isolation and characterization of cDNA and genomic clones encoding information for a third member of this hsp family (c/gMHSP18-1). DNA fragments containing nucleotide sequences common to, or specific for, each of these characterized 18-kDa genes were prepared and used as probes to assess the expression of these genes during microsporogenesis and development of the gametophyte in an inbred line of maize (Oh43). Our results demonstrate (1) that mRNA transcripts encoding the 18-kDa hsps are expressed and/or accumulate during microsporogenesis, and (2) that genes encoding two of the characterized 18-kDa hsps are expressed and/or accumulate independently, in a stage-specific manner during microsporogenesis. These observations imply that the stage-specific expression of particular 18-kDa hsp genes results from gene-specific regulation during microsporogenesis and gametophyte development rather than from an overall activation of the heat shock or stress response. PMID- 8482010 TI - Expression of endogenous and microinjected hsp 30 genes in early Xenopus laevis embryos. AB - In the present study, we have examined the regulation of expression of a newly isolated member of the hsp 30 gene family, hsp 30C. Using RT-PCR, we found that this gene was first heat-inducible at the tailbud stage of development. We also examined the expression of two microinjected modified hsp 30C gene constructs in Xenopus embryos. One of the constructs had 404 bp of hsp 30C 5'-flanking region, whereas the other had 3.6 kb. Both gene constructs had 1 kb of 3'-flanking region. RT-PCR assays were employed to detect the expression of these microinjected genes. The presence of extensive 5'- and 3'-flanking regions of the hsp 30C gene did not confer proper developmental regulation, since heat-inducible expression of both of the microinjected constructs was detectable at the midblastula stage. The premature expression of the microinjected hsp 30 gene was not a result of high plasmid copy number of the presence of plasmid DNA sequences. These results suggest that the microinjected genes contain all the cis acting DNA sequences required for correct heat-inducible regulation but do not contain the elements required for the proper regulation of hsp 30 gene expression during development. It is possible that regulatory elements controlling the developmental expression of the hsp30 genes may reside upstream or downstream of the entire cluster. PMID- 8482011 TI - The induction of pyruvate kinase synthesis by heat shock in Xenopus laevis embryos. AB - Heat-shocked Xenopus embryos have an unusually complex heat shock response. The dominant heat shock protein (Hsp) has a relative molecular mass (M(r)) of 62,000 D (Hsp62). Affinity-purified IgGs against the glycolytic enzyme pyruvate kinase (PK; EC 2.7.1.40) specifically immunoprecipitated Hsp62 from extracts of embryos that had been heat-shocked at 37 degrees C for 30 min. Thus, Hsp62 and pyruvate kinase are immunologically cross-reacting. Electrophoretic separation of PK isoforms suggests that heat-shocked Xenopus embryos increase synthesis of an isoform of PK. Thermal denaturation studies suggest that this isoform has enhanced thermal stability. The identification of PK as an Hsp is discussed within the context of a physiological requirement for elevated levels of anaerobic glycolysis in heat-stressed cells as a vital component of the acquisition of thermotolerance. PMID- 8482012 TI - Regulation of two different hsp70 transcript populations in steroid hormone induced fungal development. AB - In the filamentous oomycete fungus Achlya, the differentiation of gamete bearing structures on vegetative hyphae of the male mating type, is induced by the Achlya steroid hormone, antheridiol. Among the several metabolically labeled intracellular proteins whose synthesis or accumulation is altered by hormone treatment are steroid-induced 85-kDa and 68- to 78-kDa proteins. The 85-kDa protein was previously shown to be the Achlya heat shock protein hsp85 [Brunt et al., 1990; Brunt and Silver, 1991], a component of the putative Achlya steroid hormone receptor. It was of interest to determine if the antheridiol-induced "70 kDa" proteins were hsp70-family heat shock proteins and if hormone treatment induced changes in the level of hsp70 transcripts. Two different Achlya hsp70 genomic sequences were cloned and used to investigate these questions. The two hsp70 sequences recognized two different mycelial transcript populations, one of which was regulated also by decreased glucose. Of note, both of the two hsp70 transcript populations were found to be regulated by antheridiol. The hormone induced changes in hsp70 transcript levels were temporally correlated with the onset of massive lateral hyphal branching and alterations in the pattern of secreted N-linked glycoproteins which occur in hormone-treated mycelia. To our knowledge, this represents one of the first reports on changes in hsp70 proteins and transcripts during fungal differentiation. Our results may have implications for the role of heat shock proteins in hyphal branching and secretion in filamentous fungi and perhaps other cell types. PMID- 8482013 TI - hsp23 and hsp26 exhibit distinct spatial and temporal patterns of constitutive expression in Drosophila adults. AB - To determine differences in the patterns of expression of Drosophila small heat shock proteins (shsp) during normal development in the absence of stress, proteins obtained from head, thorax and gonads of young (0-12 h, 3 days), middle aged (3-6 days) and 15- to 20-day-old adult flies were separated on SDS-PAGE gels and blotted with monoclonal antibodies against hsp23 and hsp26. hsp23 was found in the heads and gonads of young males and females. In contrast, the maximum expression of hsp26 was seen in gonads of young flies, and it was only lightly detected in the brain. The expression of both proteins decreased as flies aged. This age-related decrease was particularly striking for hsp23 in females. The immunoblot results obtained were complemented by immunostaining of thin parasagittal sections of whole fly bodies. Hsp23 was found to be expressed in the brain, thoracic ganglion, fat body and gonads of young (0-12 h) males and females. On the other hand, hsp26 was essentially detected in ovaries and testes of these young flies. The analysis of the tissue expression of both proteins demonstrate that each shsp has a distinct cellular localization. In the central nervous system, hsp23 and hsp26 were present in the neurocytes of the brain and the thoracic ganglion. In addition, hsp23 (but not hsp26) was also detected in the central neuropile of these two organs. In testis, hsp26 was localized in the cytoplasm of spermatocytes and, probably, in the spermatid bundles. In contrast, hsp23 was detected at the periphery of cells (membranes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482014 TI - Development and tissue-specific distribution of mouse small heat shock protein hsp25. AB - We have investigated the developmental and tissue-specific distribution of the mouse small hsp25 by immunohistology using an antibody that specifically identifies hsp25. Our analysis shows that the relative amount of hsp25 increases during embryogenesis. Through days 13-20 of embryogenesis, hsp25 accumulation is predominant in the various muscle tissues, including the heart, the bladder, and the back muscles. hsp25 is detectable also in neurons of the spinal cord and the purkinje cells. Furthermore analysis of the closely related alpha, B-crystallin shows that in several tissues, including the bladder, the notochordal sheath and the eye lens both proteins are coexpressed. Our studies demonstrate that mammalian hsp25 accumulation is developmentally regulated during mouse embryogenesis and support the view of an important functional role of small heat shock proteins in normal cell metabolism. PMID- 8482015 TI - Tissue-specific expression of heat shock proteins of the mouse in the absence of stress. AB - The steady-state levels of four members of the heat shock proteins families (HSP84, HSC73, HSP71, and HSP25) were examined by immunoblot analysis of several different tissues of young and adult mice in the absence of stress. These hsps were detected in all tissues but their level was variable. The levels of HSC73 and HSP84 varied only slightly between different tissues in either young or adult mice, with the exception of skin where these hsps were found in reduced amounts. In contrasts, the stress-inducible member of the HSP70 family, HSP71, was found to be expressed in all tissues but in amounts which differed by as much as two orders of magnitude between tissues. In general, the levels of both HSP71 and HSP25 were found to be tissue dependent, with higher levels found in tissues such as stomach, intestine, colon and bladder, tissues which are exposed to toxic environmental or metabolic products, and which may concentrate these substances by water resorption and/or be exposed to them for longer periods. The levels of HSP71 and HSP25 were generally positively correlated both in young and adult mice although this correlation was not found in certain tissues such as kidney, testes, and bone. Tissues of young mice contained lower amounts of HSP25 and HSP71 than were found in the same tissues from adults. We conclude that hsps are expressed in all tissues of the mouse in the absence of stress and that some organs, particularly those exposed to potentially toxic metabolites, show a higher level of expression of HSP71 and HSP25. PMID- 8482016 TI - HSP86 and HSP84 exhibit cellular specificity of expression and co-precipitate with an HSP70 family member in the murine testis. AB - This study extends to the protein level our previous observations, which had established the stage and cellular specificity of expression of hsp86 and hsp84 in the murine testis in the absence of exogenous stress. Immunoblot analysis was used to demonstrate that HSP86 protein was present throughout testicular development and that its levels increased with the appearance of differentiating germ cells. HSP86 was most abundant in the germ cell population and was present at significantly lower levels in the somatic cells. By contrast, the HSP84 protein was detected in the somatic cells of the testis rather than in germ cells. The steady-state levels of HSP86 and HSP84 paralleled the pattern of the expression of their respective mRNAs, suggesting that regulation at the level of translation was not a major mechanism controlling hsp90 gene expression in testicular cells. Immunoprecipitation analysis revealed that a 70-kDa protein coprecipitated with the HSP86/HSP84 proteins in testicular homogenates. This protein was identified as an HSP70 family member by immunoblot analysis, suggesting that HSP70 and HSP90 family members interact in testicular cells. PMID- 8482017 TI - Heat-shock gene expression and cell cycle changes during mammalian embryonic development. AB - Synchronized regulation of cell division during gastrulation is essential for the regional proliferation of cells and pattern formation of the early CNS. The neural plate and neuroectoderm cells are a rapidly dividing and differentiating population of cells with a unique and rapid heat-shock response. Heat shock and the heat-shock genes were studied during neural plate development in a whole rat embryo culture system at 9.5-11.5 days. A lethal shock can cause cell death and severe developmental defects to the forebrain and eye during organogenesis. Heat shock can also result in acquired thermotolerance whereby cell progression is delayed at the G1/S and S/G2 boundaries of the cell cycle. This delay in cell cycle progression caused an overall lengthening of the cell cycle time of at least 2 hr. The heat shock genes may therefore function as cell cycle regulators in neuroectoderm induction and differentiation. The kinetics and expression of the hsp genes were examined in neuroectodermal cells by flow cytometry and Northern analysis. The levels of hsp mRNA 27, 71, 73, and 88 were identified following exposure at 42 degrees C (nonlethal), 43 degrees C (lethal) and 42 degrees/43 degrees C (thermotolerant) heat shock. Examination of hsp gene expression in the neural plate showed tight regulation in the cell cycle phases. Hsp 88 expression was enhanced at Go and hsp71 induction at G2 + M of the cell cycle. Cells exposed to a thermotolerant heat shock of 42 degrees C induced hsp71 mRNA expression in all phases of the cell cycle with the mRNA levels of hsp27, 73, and 88 increased but relatively constant. Following a lethal heat shock, dramatic changes in hsp expression were seen especially enhanced hsp71 induction in late S phase. The regulated expression of hsps during the cell cycle at various phases could play a unique and important role in the fate and recovery of neuroectoderm cells during early mammalian embryo development. PMID- 8482018 TI - Lack of concordance between heat shock proteins and the development of tolerance to teratogen-induced neural tube defects. AB - The present study was undertaken to examine the role of heat shock response in the development of tolerance and cross-tolerance in an in vivo murine model of teratogen-induced neural tube defects. The experimental paradigm designed to address this question was to utilize inbred mouse strains that differed in their sensitivity to hyperthermia and valproic acid induced neural tube defects, subjecting the dams to subteratogenic pretreatments with either heat or valproic acid at two different timepoints during development prior to the administration of the teratogenic insult. A statistically significant reduction in the frequency of neural tube defects and/or embryolethality following a pretreatment in dams subsequently exposed to a teratogenic treatment was considered evidence for the induction of tolerance. This was observed in the SWV embryos exposed to the 38 degrees C pretreatment at 8:06 and to embryos exposed to either pretreatment temperature at 8:10 prior to a teratogenic heat shock at 8:12. In the LM/Bc embryos, only the 41 degrees C pretreatment at 8:06 induced thermotolerance. There was no evidence of tolerance induced in either mouse strain using valproic acid. On the other hand, cross-tolerance was clearly demonstrated in this study, with a low temperature (41 degrees C) pretreatment successfully protecting SWV fetuses from a subsequent teratogenic treatment with valproic acid, while valproic acid (200 mg/kg) was effective in reducing the risk of hyperthermia induced neural tube defects in the LM/Bc fetuses. In all instances, tolerance was induced in the absence of significant induction of hsp synthesis. The lack of concordance between hsps and thermotolerance suggests that some other factor(s) is involved in conferring thermotolerance on developing murine embryos. PMID- 8482019 TI - Changes in heat shock protein synthesis and heat sensitivity during mouse thymocyte development. AB - Heat shock protein synthesis was examined in mouse thymocytes at three stages of development: early embryonic thymocytes, which are CD4-CD8-, adult thymocytes, which are primarily CD4+CD8+, and mature spleen T cells, which are CD4+CD8- or CD4-CD8+. After either a 41 degrees C or 42 degrees C heat shock, the synthesis of the major heat-inducible protein (hsp68) was elevated during the first hour of recovery but then decreased abruptly in thymocytes from adult mice. In contrast, the synthesis of hsp68 continued for up to 4 h after heating embryonic mouse thymocytes or mature spleen T cells. The more rapid termination of the heat shock response in the adult thymocytes was not the result of either less heat damage or more rapid repair since the recovery of general protein synthesis was more severely delayed in these cells. As well, the double positive CD4+CD8+ cells were more sensitive to hyperthermia than either the double negative CD4-CD8- or single positive CD4+CD8- or CD4-CD8+ cells. Exposure of fetal thymus organ cultures to elevated temperature revealed that the double negative thymocytes were able to survive and differentiate normally following a heat shock treatment that was lethal for the double positive thymocytes. Exposure of thymocytes from adult mice to elevated temperatures induced apoptotic cell death. This was evident by the cleavage of DNA into oligonucleosome-sized fragments. Quantitation of the extent of DNA fragmentation and the number of apoptotic cells by flow cytometry demonstrated that the extent of apoptotic cell death was related to the severity of the heat stress. Double positive (CD4+CD8+) thymocytes are selected on the basis of their T-cell antigen receptor (TCR). Most of these cells are negatively selected and die within the thymus by an active process of cell deletion known as apoptosis. Restricting hsp synthesis in response to stress might be essential during developmental processes in which cell maturation is likely to result in death rather than functional differentiation. PMID- 8482020 TI - Heat shock gene expression and development. II. An overview of mammalian and avian developmental systems. PMID- 8482021 TI - Activity of a microinjected inducible murine hsp68 gene promoter depends on plasmid configuration and the presence of heat shock elements in mouse dictyate oocytes but not in two-cell embryos. AB - After fertilization in the mouse, the zygotic genome is activated in two-cell embryos by the spontaneous expression, among other genes, of the major inducible heat shock gene, hsp68, in the absence of heat-inducibility of heat shock genes. To obtain information on this phenomenon, we have probed one- and two-cell embryo's ability to express microinjected reporter DNA constructs, containing the Escherichia coli lacZ gene driven by promoters from early SV40 genes, the human beta-actin gene, and the normal or HSE-deleted mouse hsp68 gene. Activity of these promoters was also tested in mouse granulosa cells and dictyate oocytes, as a function of circular/linear construct configuration and occurrence of heat shock. The hsp68 promoter was heat-inducible in both granulosa cells and oocytes. Its heat activation required the presence of HSEs and, in the oocytes, of construct linear configuration. In the embryos however, this promoter was expressed independently of the presence of HSEs and of construct configuration, and its activity was not affected by heat shock. When constructs with early SV40 and beta-actin promoters were injected into one-cell embryos, they appeared to be inactivated with the first embryonic cleavage, in agreement with previous observations [Wiekowski et al., 1992]. By contrast, both normal and HSE-deleted hsp68 promoters maintained their activity through the first cleavage, providing the first evidence of a gene escaping such transcriptional repression. Present results confirm previous findings on hsp68 expression during early mouse development, and suggest that this activation is mediated by a factor(s) other than HSF. PMID- 8482022 TI - The variability of processing of technetium-99m DTPA renography. Role of interpolative background subtraction. AB - In quantitative renography, observer-dependent selection of renal outlines and background regions may account for considerable variability. This study of differential renal function with Tc-99m DTPA scintigraphy compares interpolative background subtraction with the authors' routine techniques; the latter involves background-subtracted uptake on data integrated over 1-3 minutes after injection. Other techniques considered were omission of background subtraction and use of 1 2 minute integration. The normal range was established in 24 hypertensive patients who had a normal angiogram and a normal radiometric glomerular filtration rate. The test set of 52 other hypertensive patients included 27 with renal artery stenosis. All techniques correlated well with the routine method (r > or = 0.98); however the interpolative background technique was unique in preserving the depiction of renal asymmetry but reducing the variability of replicate measurements (P < 0.05). Reduced renal function increased the variability of routine measurements, but the interpolative background subtraction method performed better in this instance (P < 0.01). Thus, the new technique appears to improve the definition of renal outlines and increase the reliability of measurements of differential renal function. PMID- 8482023 TI - Estimating renal function from the visual analysis of Tc-99m DTPA images. AB - Eleven visual parameters of Tc-99m DTPA imaging studies were evaluated to identify scintigraphic findings that best detect changes in renal function, to determine at which GFR levels they appear, and to establish criteria for visual estimation of renal function. Visual parameters were compared to in vitro GFR determinations in 41 patients. Three visual parameters offered best discrimination. The first one appeared at GFR values below 70 mL/min (sensitivity: 76%). The renal peak activity on the flow study (normally equal or greater than aortic) no longer reached the intensity of the aortic peak (pK < pA). The second parameter appeared at GFR values below 50 mL/min (sensitivity: 85%). The estimated kidney-to-liver ratio in the 2-minute image (usually 3 or greater) decreased to values less than 3. The third scintigraphic finding, pelvicalyceal system nonvisualization, appeared at GFR levels below 20 mL/min (sensitivity 100%). Use of these 3 scintigraphic findings allows categorization of patients into four functional groups: 1) severe dysfunction (GFR: 0-20 mL/min), 2) moderate to severe dysfunction (GFR: 21-50 mL/min), 3) moderate dysfunction (GFR: 50-70 mL/min), and 4) Normal study (GFR > 70 mL/min). Visual analysis of Tc-99m DTPA images does not identify patients with mildly decreased renal function (GFR: 70-90 mL/min). PMID- 8482024 TI - Evaluation of myocardial perfusion and function by technetium-99m methoxy isobutyl isonitrile before and after percutaneous transluminal coronary angioplasty. Preliminary results. AB - Myocardial perfusion and function were evaluated with Tc-99m MIBI myocardial scintigraphy before and after percutaneous angioplasty in six patients. In addition to conventional stress-rest images (3 projections: 45 degrees left anterior oblique, anterior, and left lateral), gated images were obtained at rest and during stress before and after angioplasty. Improvement in myocardial perfusion after angioplasty was demonstrated in all patients. The increase from rest to stress of radionuclide fractional shortening (an index of global left ventricular function computed on gated images) was greater after angioplasty than before (9% +/- 7% versus--0.5% +/- 8%, respectively, p < 0.05). Systolic wall thickening (an index of regional left ventricular function) showed a significantly greater rest-to-stress increase after angioplasty than before it in the regions supplied by treated vessels. Thus, Tc-99m MIBI myocardial scintigraphy is capable of evaluating myocardial perfusion and function. PMID- 8482025 TI - Basal interventricular septal thallium-201 defects: real or artifact? AB - Misinterpretation of reversible defects at the base of the interventricular septum is perhaps among the greatest single causes of false positive TI-201 myocardial perfusion images. This is a report of a patient with angiographically documented ischemia at the base of the septum and corresponding reversible defects as seen using TI-201 imaging. Illustrated are two different forms of malalignment artifact that duplicate this patient's findings in a patient with normal perfusion. PMID- 8482026 TI - Spurious lung metastases on radioiodine thyroid and whole body imaging. AB - In patients with differentiated thyroid cancer, radioiodine uptake in the area of the lung usually denotes metastasis; however, it could represent an uptake by unrelated pulmonary disease or by the breasts, or external contamination. In this study, 22 foci that simulated lung metastasis on 11 thyroid and whole body scans were proven not to be metastasis by reimaging after cleaning (15 foci), or were strongly suspected to be due to external contamination because of the features of other images (7 foci). All foci were noted only on anterior views of the chest. Of the 22 foci, 19 were focal, two were smeared, and one was lobar. Foci were multiple in 7 scans, unilateral in 10 scans, and were associated with other artifacts in 4 scans. Caution should be used in interpreting apparent pulmonary radioiodine uptake as lung metastasis; reimaging after cleaning the skin and changing garment should be obtained when the uptake is confined to anterior views of the chest and/or when its pattern is atypical. PMID- 8482027 TI - Reverse mismatch between perfusion and aerosol ventilation in transplanted lungs. AB - Thirty ventilation-perfusion pulmonary scintigraphic studies were performed in 13 patients who had undergone unilateral lung transplantation. Ventilation-perfusion mismatch (ventilation better than perfusion) was judged absent, mild, moderate, or severe in the transplanted and native lungs. Ventilation-perfusion mismatch was significantly worse in the transplanted lungs (p < .0001). Findings of lung biopsies and chest roentgenograms failed to correlate with the severity of ventilation-perfusion mismatch. Hypoxic pulmonary vasoconstriction appears to be significantly impaired in most unilateral lung transplants; the mechanism for this impairment is unclear. PMID- 8482028 TI - Bile duct leakage after laparoscopic cholecystectomy diagnosed by radioisotopic scanning. AB - Laparoscopic cholecystectomy is fast becoming the procedure of choice for removal of the gallbladder. It offers advantages over traditional cholecystectomy with shorter hospital stays, less postoperative pain, and lowered hospital costs. Laparoscopic cholecystectomy has been shown to be a safe procedure when performed by experienced surgeons, but a higher incidence of injury to the bile duct has been noted. Nuclear scintigraphy offers a noninvasive method for the diagnosis of traumatic injury to the bile duct. A case is presented in which a patient developed a major bile duct leak after undergoing an apparent successful laparoscopic cholecystectomy. The complication was promptly diagnosed through the use of nuclear scintigraphy. Radioisotopic scanning should be considered when evaluating patients who manifest abdominal pain after laparoscopic cholecystectomy. PMID- 8482029 TI - Correlation between bone imaging and the clinical picture in two unsuspected cases of progressive diaphyseal dysplasia (Engelmann's disease). AB - Progressive diaphyseal dysplasia was incidentally discovered in two patients referred for Tc-99m MDP bone scintigraphy (one for intense sciatica, the other for the detection of breast cancer metastases). Tracer accumulation in the diaphyses of the lower limbs and the base of the skull was accompanied by bone thickening and patency of the medullary cavity, as demonstrated by radiography, MRI, and bone marrow scanning. Comparison of the clinical pictures with the results of instrumental examinations showed that these were cases of sporadic progressive diaphyseal dysplasia of slight and average gravity, respectively. The differentiation of Ribbing's disease is explained and reference also is made to a finding not mentioned in the literature, namely frontal bone resorption lacunules in one patient. PMID- 8482030 TI - A comparative I-123 IMP SPECT study in Binswanger's disease and Alzheimer's disease. AB - The regional cerebral blood flow in 31 patients was semiquantitatively measured with SPECT using N-isopropyl iodo-amphetamine (I-123 IMP). Of the 31 patients, 9 had Binswanger's disease (BD) (mean age: 64.2 years), 10 had Alzheimer's disease (AD) (mean age: 66.8 years), and 12 were neurologically normal (mean age: 67.8 years). Tracer activity was determined in 7 pairs of cerebellar, cortical, and subcortical regions and was expressed as two ratios: the activity in each region of interest (ROI) compared to the mean count in the cerebellar region (ROI/CER ratio) and compared to the mean count in the occipital cortex (ROI/OCC ratio). Patients with BD showed a reduction of the ROI/CER ratio in the temporal cortex, thalamus, and basal ganglia compared to normal subjects. However, the ROI/CER ratio for the occipital region was higher than that of normal controls, suggesting that cerebellar blood flow was reduced in patients with BD. AD patients showed a decreased ROI/CER ratio in the frontal, temporal, and parietal cortices. Both BD and AD patients showed decreased ROI/OCC ratios in all the cortical and subcortical regions compared to the neurologically normal patients. In BD patients, the most marked reduction of both ratios was found in the thalamus, while for AD patients the most prominent reduction was seen in the parietal cortex. Our results indicate that these two types of dementia show characteristic regional cerebral blood flow patterns, which may be associated with their clinical features. PMID- 8482031 TI - Role of Ga-67 citrate imaging in extrapulmonary pneumocystis in HIV positive patients. PMID- 8482032 TI - Localization of Tc-99m MDP in a ureteral tumor. PMID- 8482033 TI - A comet-tail imaging artifact. Due to a "hot" point source and faulty electronics. PMID- 8482034 TI - Scintigraphic detection of a pleuro-biliary fistula. Post-operative complication of an amebic liver abscess. PMID- 8482035 TI - Salmonella osteomyelitis in an HLA-B27 patient. PMID- 8482036 TI - Diffuse liver uptake of Tc-99m phosphate compound associated with intravenous injection of iron colloid solution. PMID- 8482037 TI - Tc-99m HDP bone scintigraphy of ameloblastoma with panorex, CT, MRI, and gross correlation. PMID- 8482038 TI - Left ventricular thrombus identification. A scintigraphic and echocardiographic correlation. PMID- 8482039 TI - Simultaneous diagnosis of acute cholecystitis, intestinal malrotation, and duodenal diverticulum by cholescintigraphy. PMID- 8482040 TI - SPECT imaging of intense bone tracer uptake by an extensive extraosseous hemangioma. PMID- 8482041 TI - Dopamine and the kidney: ten years on. PMID- 8482042 TI - Enteric disease in early childhood inhibits microvillus expression by potential stem cells. AB - 1. Enterocyte development of microvillus structure has been measured in intestinal biopsies obtained from children suffering from coeliac disease, cow's milk protein intolerance and microvillus atrophy, and the results compared with similar measurements carried out in control children. 2. All types of enteric disease caused a significant 30% reduction in the length of microvilli present on undifferentiated basal crypt enterocytes, here referred to as potential stem cells. 3. Microvillus growth measured in control enterocytes took place mainly over the basal third of the villus. There was then little further change in structure during subsequent enterocyte migration to the villus tip. 4. Microvillus length in diseased tissue remained more or less constant during enterocyte migration to the crypt-villus junction. Microvillus length then decreased slightly during subsequent enterocyte migration over stunted villi. 5. The present results are discussed in relation to the supposed properties of potential stem cells. Comparisons are also made between profiles of microvillus development measured in healthy children and mature adults. PMID- 8482043 TI - Elevation of serum triacylglycerol concentration in association with hepatic microsomal enzyme induction after treatment with phenylbutazone and diclofenac sodium in rats. AB - 1. The relationship between serum triacylglycerol concentration and hepatic microsomal enzyme activity was examined in rats. 2. Two groups of rats were injected with diclofenac sodium at doses of 2.5 and 5 mg day-1 kg-1. A third group was injected with phenylbutazone at a dose of 20 mg day-1 kg-1. The treatment was continued for 15 days and the rats were killed 24 h after the last dose. 3. In all drug-treated rats, the serum triacylglycerol concentration and the hepatic microsomal activities of aminopyrine N-demethylase and aniline hydroxylase were significantly increased as compared with the corresponding values in control rats. The correlations between the serum triacylglycerol concentrations and the activities of the two enzymes, as indices of the hepatic microsomal activity, were highly significant. 4. These results indicate that the possibility of hypertriglyceridaemia as an adverse effect of the induction of the hepatic microsomal enzymes after the administration of phenylbutazone and diclofenac sodium should be considered. PMID- 8482044 TI - Ultrastructural characterization of platelet-activating factor-stimulated human eosinophils from patients with asthma. AB - 1. Purified human eosinophils from asthmatic patients were stimulated with platelet-activating factor in vitro and examined for morphological changes by transmission electron and light microscopy. Changes were also evaluated by morphometric analysis and were related to the platelet-activating factor stimulated release of granular eosinophil cationic protein. 2. Stimulation of eosinophils with platelet-activating factor induced a dose-dependent shape change, including the elongation of cells, loss of microvilli and the formation of lamellipodia. This effect was maximal at 25 min and was reversible. 3. Stimulation with platelet-activating factor also induced granule movement to the cell periphery and fusion of adjacent granules. Granules became swollen and vesiculated, whereas both the matrix and core showed evidence of solubilization. 4. There was a time-dependent secretion of eosinophilic cationic protein from human eosinophils upon stimulation with platelet-activating factor which occurred without significant lactate dehydrogenase release. 5. Morphometric analysis of the transmission electron micrographs indicated a significant reduction in cytoplasmic area after 10 min of incubation with platelet-activating factor from 39.0 +/- 1.7 microns 2 for untreated eosinophils to 33.2 +/- 2.3 microns 2 (P < 0.02) for platelet-activating factor-treated cells, underscoring the observation that the cells change from spherical to ellipsoidal. No significant increase in the perimeter of the cells was found. 6. The number of granule-profiles in platelet-activating factor-stimulated eosinophils was slightly reduced when compared with control, and an increase in granule area was observed 10 min after platelet-activating factor challenge (0.215 +/- 0.011 microns 2 versus 0.246 +/- 0.016 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482045 TI - A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. AB - 1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS.+ radical cation. 2. An automated method for use on a centrifugal analyser, as well as a manual method, is described. 3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard. 4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated. 5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity. PMID- 8482046 TI - Effects of oral alcohol on superior mesenteric artery blood flow in normal man, horizontal and tilted. AB - 1. The cardiovascular effects of oral alcohol (0.5 g/kg body weight diluted to 300 ml in sugar-free orange juice) were compared with those of placebo in 10 normal subjects. Measurements were made while the subjects were supine and horizontal for 45 min and after 10 min of 45 degrees head-up tilt. 2. After alcohol, plasma alcohol levels rose from 1.9 +/- 1.3 to 61.6 +/- 6.5 mg/100 ml. After placebo, plasma alcohol levels did not increase. After alcohol and placebo, supine blood pressure was unchanged; heart rate, both supine and during tilt, rose after alcohol only. 3. After alcohol, superior mesenteric artery and digital skin blood flow increased and calculated vascular resistances fell. There was no change after placebo. 4. Forearm blood flow, forearm vascular resistance and cardiac index did not change in either phase, except for a fall in cardiac index during tilt but only after alcohol. 5. In conclusion, the acute ingestion of 0.5 g of alcohol/kg body weight in normal subjects raised heart rate and actively dilated the superior mesenteric artery and digital skin vessels. There was no effect on blood pressure, cardiac output and skeletal muscle vascular tone. During head-up tilt after alcohol, there was a tendency for blood pressure to fall with a compensatory rise in heart rate. PMID- 8482047 TI - Endothelium-dependent modulation of responses to endothelin-I in human veins. AB - 1. We have investigated whether local vascular production of nitric oxide or prostacyclin regulates venoconstriction induced by the endothelium-derived peptide, endothelin-1, in vivo in man. 2. Six healthy subjects received local dorsal hand vein infusion of endothelin-1 for 60 min alone or, on two separate occasions, co-infused with the donator of nitric oxide, glyceryl trinitrate, or the vasodilator prostaglandin, prostacyclin. In further studies, endothelin-1 was co-infused with an inhibitor of nitric oxide production, NG-monomethyl-L arginine, or after oral administration of the irreversible inhibitor of prostaglandin production, acetylsalicylic acid (aspirin). 3. At a low dose (5 pmol/min), endothelin-1 alone caused slowly developing and long-lasting venoconstriction (maximal constriction: 66 +/- 4%). Although glyceryl trinitrate partially prevented endothelin-1-induced venoconstriction (maximum: 33 +/- 5%), inhibition of nitric oxide production did not affect endothelin-1-induced venoconstriction (maximum: 55 +/- 4%). 4. Prostacyclin was more effective at blocking the venoconstriction in response to endothelin-1 than glyceryl trinitrate (maximum: 12 +/- 3%), and there was substantial potentiation of endothelin-1-induced venoconstriction after pretreatment with aspirin (maximum: 90 +/- 3%). 5. Despite the capacity of nitric oxide to attenuate responses to endothelin-1, NG-monomethyl-L-arginine did not potentiate endothelin-1-induced venoconstriction, suggesting little or no stimulated production of nitric oxide in human veins. However, the potentiation of responses to endothelin-1 by aspirin indicates that endothelial production of prostacyclin attenuates responses to endothelin-1 in human veins in vivo. PMID- 8482048 TI - Long-term insulin treatment of vascular smooth muscle cells from rat aorta attenuates the synergistic effect of insulin on angiotensin II- and epidermal growth factor-induced DNA synthesis. AB - 1. In the present study the effects of acute and chronic insulin treatment on growth factor-induced cell growth were investigated in vascular smooth muscle cells. Cell growth was quantified by the incorporation of [3H]thymidine into cell DNA and by determination of total protein. 2. Insulin in a concentration range of 10(-9)-10(-6) mol/l had no effect on cell DNA synthesis. Insulin-like growth factor-1 in a concentration range of 10(-9)-10(-6) mol/l induced a concentration dependent increase in total cell protein, whereas no changes in DNA synthesis were observed. 3. Acutely, insulin enhanced the mitogenic effect of epidermal growth factor and angiotensin II. Long-term treatment with 10 and 100 ng/ml insulin over 14 weeks was associated with a time-dependent reduction in this potentiating effect of insulin on growth factor-induced DNA synthesis. To evaluate the mechanism of this effect, receptor binding studies were performed with 125I-labelled insulin-like growth factor-1. No difference in the Kd value (2.1 nmol/l) for insulin-like growth factor-1 was found between untreated and chronically insulin-treated cells, whereas the maximal number of binding sites decreased from 5.9 x 10(4) (untreated cells) to 4.7 x 10(4) (10 ng/ml) and to 4.3 x 10(4) (100 ng/ml) binding sites/cell in chronically insulin-treated cells. 4. We conclude that insulin acutely enhances the mitogenic effect of various growth factors such as epidermal growth factor and angiotensin II on vascular smooth muscle cells. Long-term insulin treatment reduced the number of receptor binding sites for insulin-like growth factor-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482049 TI - Treatment of anaemia in haemodialysis patients with erythropoietin: long-term effects on exercise capacity. AB - 1. The effects of correcting anaemia on exercise capacity were evaluated in 21 haemodialysis patients (aged 39 +/- 12 years) before starting treatment with recombinant human erythropoietin (Hb concentration, 73 +/- 10 g/l; total Hb, 59 +/- 12% of expected), after correction of the anaemia to a Hb concentration of 108 +/- 7 g/l and a total Hb 82 +/- 10% of expected, and in 13 of the patients after 12 months on maintenance recombinant human erythropoietin treatment (Hb concentration 104 +/- 14 g/l, total Hb 79 +/- 17% of expected). Fifteen healthy subjects (aged 41 +/- 9 years), who took no regular exercise, constituted the control group. Maximal exercise capacity was determined on a bicycle ergometer. Oxygen uptake, respiratory quotient, blood lactate concentration, heart rate and blood pressure were measured at rest and at maximal workload. 2. After 6 +/- 3 months on recombinant human erythropoietin, maximal exercise capacity increased from 108 +/- 27 W to 130 +/- 36W (P < 0.001) and the maximal oxygen uptake increased from 1.24 +/- 0.39 litres/min to 1.50 +/- 0.45 litres/min (P < 0.001). No significant changes in respiratory quotient (1.16 +/- 0.13 versus 1.18 +/- 0.13) and blood lactate concentration (4.0 +/- 1.8 versus 3.6 +/- 1.1 mmol/l) at maximal workload were observed, but the blood lactate concentration in the patients was significantly lower than that in the control subjects (6.7 +/- 2.3 mmol/l, P < 0.01). After the correction of anaemia, the aerobic power was still 38% lower in the patients than in the control subjects and 17% lower than the reference values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482050 TI - Effect of posture and acute glycaemic control on the excretion of retinol-binding protein in normoalbuminuric insulin-dependent diabetic patients. AB - 1. It has been suggested that tubular damage may precede glomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein. 2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load. 3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded. 4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482051 TI - Glucose-dependent uptake of chromium in human and rat insulin-sensitive tissues. AB - 1. This study was designed to investigate the influence of insulin and glucose on the distribution of trivalent chromium in human plasma and blood cells and in human and rat insulin-sensitive and -insensitive tissues. 2. Evidence is provided that, in the rat in vitro, a clear difference exists in chromium binding between insulin-sensitive and -insensitive tissues in that chromium binding is significantly enhanced by glucose in insulin-sensitive tissues. 3. Glucose dependent association of chromium with human adipose tissue was blocked by inhibitors of glucose transport. 4. Addition of insulin slightly increased the response to glucose in muscle and reduced the response to glucose in adipose tissue; such effects were less marked than those seen in response to glucose alone. 5. The results of this study in vitro support the hypothesis that, in vivo, chromium translocates from the blood compartment to insulin-sensitive tissues. PMID- 8482052 TI - Sulphation in the colon. PMID- 8482053 TI - Will health care demand continue to increase? PMID- 8482054 TI - The Colorado Women's Cancer Control Initiative: a comprehensive effort to address breast and cervical cancer in Colorado women--Part 1. PMID- 8482055 TI - A Friendship Bridge from the United States to Vietnam. PMID- 8482056 TI - Emergency consultation for HMO-hospital patients. PMID- 8482057 TI - Let's talk about America's health system. PMID- 8482058 TI - [Physical activity and osteoporosis]. AB - The aim of the present research was to underline the importance of physical activity in the prevention and treatment of osteoporosis. Therefore the authors considered age-related bone loss and the value of weight-bearing exercise on bone remodeling. Moreover the authors examined current world literature on physical exercise in post-menopausal age and bone mineral content in athletes, reporting their study's results. PMID- 8482059 TI - [Congestive heart failure with frequent hospital readmissions in the elderly]. AB - Ten elderly patients with heart failure and frequent hospital readmission within 12 months before the study, were submitted to clinical radiologic, electrocardiographic and echocardiographic evaluation in order to find the causes of readmission. The most frequent factors were found to be non compliance with drug prescriptions and therapy inadequate for the etiology of the heart failure and the kind of cardiac dysfunction. PMID- 8482060 TI - [Chronic administration of lithium and rubidium in rats. General behavior, explorative behavior and electric activity of the brain]. AB - We have studied the rat under chronic treatment with lithium carbonate and rubidium chloride both given ip. For a four week period we have recorded, once a week, weight, rectal temperature, tail-flick, motor co-ordination and general activity in a one-arm radial maze and in a Boissier-Simon table. At the end of the fourth week surface (SEEG) and deep EEGrams (DEEG: hippocampus, amygdala) were recorded from treated and control animals. FFT (Hanning window) was performed both for SEEG and DEEG. The findings are: 1) No changes in weight, rectal temperature, tail-flick and motor coordination (rotarod). 2) In the one arm maze and in the Boissier-Simon table rubidium is in contrast to the effects of lithium, it causes increased activity and aggression 3) the EEGrams were analyzed by means of FFT as power in preselected bands of frequency. The results, on the whole, suggest, since these two ions have opposite effects on brain norepinephrine metabolism, that they may be useful in the treatment of PMD. PMID- 8482061 TI - [Atypical retinitis pigmentosa in Laurence-Moon-Biedl-Bardet syndrome. Report of a case of chronic renal insufficiency under periodic hemodialysis treatment]. AB - A case of Laurence-Moon-Biedl-Bardet syndrome in a patient undergoing hemodialysis is reported. The principal characteristics of this congenital syndrome are described. A possible pathogenetic mechanism of the atypical form of retinitis pigmentosa (sine pigmento) is discussed. PMID- 8482062 TI - [Effectiveness and tolerability of simvastatin in subjects with primary hypercholesterolemia. Multicenter study]. AB - The efficacy and safety of simvastatin were evaluated in an open multicenter study over a 24-week period. One hundred seventy-two patients (91 men, 81 women) with primary hypercholesterolemia (mostly polygenic) were enrolled in 14 Centers in Northern Italy. The mean age was 55.8 +/- 9.7 years and the mean baseline total cholesterol level was 305 +/- 59 mg/dL. After 4 weeks on an AHA step 1 diet, patients who met the inclusion criterion (total cholesterol > or = 250 mg/dL) were given simvastatin 10 or 20 mg in the evening. The dose could be titrated up to a maximum of 40 mg o.d. at week 6 and 12. No dose titration was allowed after week 12. One hundred forty-nine patients (86.6%) completed the study according to the protocol, 2 (1.2%) were withdrawn from the study because of adverse events not related to the drug, 21 (12.2%) were unavailable for follow up. Simvastatin treatment was associated with a sustained dose-related reduction in total and LDL cholesterol (-28% and -39% respectively at the end of the study). Triglycerides showed a significant descending trend (-16% at week 24) and HDL-C increased by 9%. Apolipoproteins were measured in only 25 patients: apo B was reduced by 30% and apo A1 increased by 9%. Clinical side effects were not relevant. Mean levels of GOT, GPT and CPK significantly increased after 6 weeks on simvastatin, but remained stable and at any rate ioitlin the normal range thereafter. Eight patients (5.4%) experienced small transaminase level elevations (< 3ULN) and six (4%) small CPK elevations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482063 TI - [Evaluation of the clinical efficacy of misoprostol for gastric cytoprotection in patients under treatment with NSAID after proctologic intervention]. AB - To perform ambulatorial surgery with local anaesthetics, it is important to carry out a correct postsurgical NSAID therapy avoiding the risks induced by these drugs. Two groups of patients submitted to ambulatorial hemorrhoidectomy were enrolled in a randomized study to evaluate the safety of NSAID therapy with or without the coadministration of misoprostol, a PGE1 analogue with gastroprotective action. Aim of this study was to evaluate if misoprostol in coadministration with NSAID could permit a correct domiciliary postsurgical NSAID therapy without gastric symptoms related to the NSAID therapy. From January 1990 to December 1991, 95 patients underwent hemorrhoidectomy and were discharged with analgesic therapy: the first group (n = 45) without gastroprotective therapy, the second group (n = 50) with the coadministration of misoprostol 200 mcg bid. After 7 and 14 days of treatment patients showed the following symptoms: in the first group 13.3% of the cases showed mild epigastric pain, 8.8% moderate epigastric pain and 4.4% severe epigastric pain with heartburn; in the second group (NSAID + misoprostol) only 4% of the cases showed moderate epigastric pain. The incidence of epigastric pain was statistically higher (p < 0.05) in patients treated with NSAID alone in comparison with the group treated with NSAID + misoprostol. The results, according to international literature, show that correct gastro protective therapy with synthetic prostaglandins (misoprostol) is necessary for patients in treatment with NSAIDs. PMID- 8482064 TI - [Therapeutic use of metadoxine in chronic alcoholism. Double blind study of patients in a department of general medicine]. AB - Sixty patients, recognized as chronic alcoholics on the grounds of the case history and with a score above 11 of the Munich Alcoholism Test (MALT) have been treated with metadoxine or placebo for thirty days according to a double blind randomized design. In the group treated with active drug there has been a significant reduction higher than in the controls of the scores relating to the abstinence symptomatology, in particular regarding the neuropsychic residual symptomatology (anxiety, depression, insomnia) after the first week of treatment, a reduced requirement of benzodiazepines and/or neuroleptics, and a significant decrement higher than in the controls of the score of MALT at the end of treatment. Furthermore, metadoxine seems to make easy the maintenance of abstinence, at least at short term. PMID- 8482065 TI - [Vanadium, an indispensable trace element in living organisms. Current data on biochemical, metabolic levels and therapeutic doses]. AB - Having briefly analyzed the role of vanadium in living organisms, the author describes conditions induced by vanadium poisoning and deficit. The most recent acquisitions concerning the use of vanadium in the treatment of diabetes mellitus and its consequent role in the prevention of atherosclerosis are also illustrated. PMID- 8482066 TI - [Vitamins. How, when, why]. PMID- 8482068 TI - Abstracts of scientific papers and posters presented at the British Diabetic Association's Medical and Scientific Section spring meeting 1-2 April 1993, University of Liverpool. PMID- 8482067 TI - [Aspirin: as recommended by WHO]. PMID- 8482069 TI - Spatial perspective-taking in conversation. AB - Speakers can describe the locations of objects from their own perspective ("on my left" or "on the left"), their addressee's ("on your right" or "on the right"), or some perspective that avoids choosing one or the other person ("closer to both of us"). This study shows that speakers set spatial perspectives differently with actual conversational partners than with the usually studied imaginary addressees. Speakers with partners tended to use more egocentric perspectives than solo speakers. Pairs varied idiosyncratically in the perspective-setting strategies they picked, but all engaged in the same collaborative process: talking until both were sure they had understood each other. When conversational roles switched, the new speakers allocated spatial perspectives with remarkable precision, taking their partners' perspectives just as often as the partner had taken theirs. Speakers were more explicit about whose perspective they were taking when they held the floor for only one description than when they gave many descriptions in a row. PMID- 8482070 TI - What's lost in inverted faces? AB - Disproportionate inversion decrements for recognizing faces and other homogeneous stimuli are often interpreted as evidence that experts use relational features to recognize stimuli that share a configuration. However, it has never directly been shown that inversion disrupts the coding of relational features more than isolated features. Here we report three studies that compare inversion decrements for detecting changes that span the isolated-relational features continuum. Relatively large inversion decrements occurred for relational features (Thatcher illusion changes, internal feature spacing), with smaller decrements for isolated features (presence/absence of facial hair or glasses). The one discrepancy was a relatively large inversion decrement for detecting changes to the eyes and mouth, which we had classified as an isolated feature change. However, this decrement disappeared when the features were presented out of the face context (Experiments 2 and 3), suggesting that it occurs because subjects spontaneously code relations between the features and the rest of the face. Although the results support the interpretation of disproportionate inversion effects as evidence of relational coding, the difficulty of classifying changes as isolated or relational highlights an undesirable ambiguity in the isolated-relational feature distinction. We therefore consider alternative construals of the configural coding notion. PMID- 8482071 TI - Testing a non-decompositional theory of lemma retrieval in speaking: retrieval of verbs. AB - Theories of lexical access in speaking differ in whether they assume that words are accessed in a conceptually decomposed or non-decomposed way. In this paper, two experiments are reported that test the non-decompositional theory and computer model proposed by Roelofs (1992a). Subjects had to name pictured actions using verbs and ignore distractor verbs superimposed on the pictures. According to the theory, semantic inhibition should be obtained from distractor cohyponym verbs that are the names of other pictures in the experiment. By contrast, semantic facilitation should be obtained from hyponyms of the target verbs. Both predictions were empirically confirmed, both qualitatively and quantitatively. These findings support the proposed non-decompositional theory and computer model. Furthermore, they refute a recent attempt to deal with a class of retrieval problems within the decompositional framework. Bierwisch and Schreuder (1992) propose to solve the hyperonym problem (Levelt, 1989) by an inhibitory channel in the mental lexicon between a word and its hyperonyms. This predicts semantic inhibition by hyponyms, instead of the observed facilitation. PMID- 8482072 TI - Word and world order: semantic, phonological, and metrical determinants of serial position. AB - Animacy, word length, and prosody have all been accorded prominent roles in explanations for word order variations in language use. We examined the sequencing effects of these factors in two types of tasks. In recall tasks designed to simulate language production, we found selective effects of animacy. Animate nouns tended to appear as subjects in transitive sentences, but showed no special affinity for initial position in conjunctions within sentences, but showed no special affinity for initial position in conjunctions within sentences, suggesting a stronger involvement of animacy in grammatical role assignment than in word ordering. Word length had no significant impact: Shorter words did not appear earlier than longer words within sentences or within isolated conjunctions of nouns. Prosody had a weak effect on word order in isolated conjunctions, favoring sequences with alternating rhythm, but only in the absence of an animacy contrast. These results tend to confirm a hypothesized role for conceptual (meaning-based) accessibility in grammatical role assignment and to disconfirm a hypothesized role for lexical (form-based) accessibility in word ordering. In a judgment task, forms with animate nouns early were preferred across all constructions, and forms with short words early were often preferred both in sentences and in conjunctions. The findings suggest a possible asymmetry between comprehension and production in functional accounts of word order variations. PMID- 8482073 TI - Somatic mutations and cellular aging. PMID- 8482074 TI - cDNA clones from fish optic nerve. AB - 1. The present review describes the results of a cloning that was successfully employed in the study of optic nerve regeneration in fish. 2. Three intermediate filaments (IFs) expressed by the glial fish optic nerve were cloned. 3. By the use of this approach it was possible to resolve the controversial question of whether glial fibrillary acidic protein (GFAP) is expressed in the fish optic nerve. 4. Moreover, as a result of the information that emerged from the cloning, it was possible to raise well-characterized monospecific antibodies and successfully exploit them in order to determine glial cell maturation, lineage and plasticity, monitor the glial cell response to injury of the fish optic nerve, and compare it to that of a non-regenerative system. PMID- 8482075 TI - Antioxidant properties of di- and polyamines. AB - 1. One diamine, putrescine and two polyamines, spermidine and spermine (PAs) of different concentrations, were processed through antioxidant systems in order to study their antioxidant effects. The systems investigated were as follows. 2. "Oxidative stress" was induced in RBCs to investigate filtration parameters, the effect of reduced glutathione (GSH) and the change in lipid peroxidation (LP) superoxide dismutase (SOD) activities. 3. Initiated LP-decreasing characteristics of the substances were studied in pig brain homogenate. 4. The LP-decreasing effect of these PAs were studied in guinea-pig heart tissue homogenate perfused with Tyrode solution, stimulated, and then perfused by the Langendorff method. 5. In all three tests, the antioxidant characteristics of PAs were unambiguously proved. PMID- 8482076 TI - Specific adenosine phosphorylase from hepatopancreas of gastropod Helix pomatia. AB - 1. Specific adenosine phosphorylase from Helix pomatia hepatopancreas was separated from inosine-guanosine phosphorylase and purified 100-165 times; molecular weights were found to be 71,000 and 90,000, respectively. 2. The enzyme is specific for deoxy- and adenosine; it is inactive for 5'-methylthioadenosine and 5-amino-4-imidazole-carboxyamide riboside. Its sensitivity to several inhibitors differs from that of eucaryotic and bacterial purine nucleoside phosphorylases, and is not identical with the sensitivity of the S. mansoni adenosine-splitting enzyme. 3. H. pomatia adenosine phosphorylase differs in its mol. wt and Km values for P(i), ribose 1P, Ado and Ade from adenosine phosphorylase of B. subtilis. PMID- 8482077 TI - Aromatic alcohol oxidase and aldehyde oxidase activities in the digestive gland of three species of terrestrial gastropod (Helix aspersa, Arion ater, Limax flavus). AB - 1. Digestive gland homogenates of three species of terrestrial gastropod mollusc were used to prepare sources of soluble aldehyde oxidase and solubilized aromatic alcohol oxidase activities. 2. The snail (Helix aspersa) had two aldox isoenzymes each able to utilize salicylaldehyde whereas two slug species had a single apparent activity inhibitable by salicylaldehyde. 3. Aromatic alcohol oxidase activities of the three gastropods differed somewhat in their relative abilities to oxidize various methoxy-benzyl and amino-benzyl alcohols but, unlike fungal aromatic alcohol oxidase, were all able to utilize crotonyl alcohol as substrate. PMID- 8482078 TI - Prediction of protein antigenic sites in human corticotrophin-releasing hormone precursor. AB - 1. The primary structure of human corticotrophin-releasing hormone precursor (h pre-proCRH) has been analysed using a number of computer algorithms to identify the areas of highest predicted antigenicity. 2. These results were correlated with crossreactivity data obtained from studies of antibodies produced in rabbits by immunizing with h pre-proCRH, and a number of related peptides. 3. Six areas of high predicted antigenicity were identified in h pre-proCRH by the prediction routines utilized. Two of these corresponded almost exactly to the two putative cleavage sites of the prohormone, and a third lay within the C-terminal region of one of the products of post-translational processing of the prohormone, i.e. CRH(1-41). 4. Experimental crossreactivity data also indicated that a number of structural factors (e.g. Omega loops, peptide conformation) may also be involved in recognition of peptide fragments by antibodies. PMID- 8482079 TI - Comparative study of biochemical parameters and kinetic properties of dopamine beta-hydroxylase activity from cat and rat adrenals. AB - The specific adrenal dopamine-beta-hydroxylase activity measured in cat and rat was: (1) two times higher in cat than in rat; (2) significantly enhanced by ascorbate (up to 5 mM) that acts as a major activator; (3) differently affected by exogenous copper added to the incubation medium, leading to a decrease with large concentrations; and (4) similar, according to the kinetic parameters, thereby demonstrating a greater affinity for ascorbate than for tyramine. PMID- 8482080 TI - Comparative nuclear magnetic resonance studies of diffusional water permeability of red blood cells from sheep and cow. AB - 1. The diffusional water permeability (p) of sheep and cow red blood cell (RBC) membrane has been monitored by a doping nuclear magnetic resonance (NMR) technique on control cells and following inhibition with p-chloromercuribenzene sulfonate (PCMBS). 2. There were no significant differences in the water permeability of sheep and cow RBCs, the values of p being around 3 x 10(-3) cm/sec at 20 degrees C and 5 x 10(-3) cm/sec at 37 degrees C. 3. Systematic studies of the effects of PCMBS on water diffusion indicated that in both species the maximal inhibition is reached in 60-90 min at 37 degrees C with 1 mM PCMBS. 4. The degree of inhibition increased as the temperature of measurement decreased, regardless of PCMBS concentration and incubation time. 5. The values of maximal inhibition ranged from 60-70% at 20 degrees C to 50-60% at 37 degrees C in the case of sheep RBCs, and from 45-55% at 20 degrees C to 40-50% at 37 degrees C in the case of cow RBCs. 6. The basal permeability to water of sheep RBCs was estimated as 1.0 x 10(-3) cm/sec at 20 degrees C and 2.2 x 10(-3) cm/sec at 37 degrees C, and that of cow RBCs as 1.6 x 10(-3) cm/sec at 20 degrees C and 2.7 x 10(-3) cm/sec at 37 degrees C. 7. In both species the activation energy of water diffusion was around 23 kJ/mol in control cells and reached values of around 30 kJ/mol after incubation with PCMBS in conditions of maximal inhibition of water diffusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482081 TI - Detection of the 9-kDa vitamin D-dependent calbindin gene in a fruit bat (Rousettus aegyptiacus) fibroblast cell line. AB - 1. A fibroblast cell line was established from skin and lung tissue of the fruit bat (Rousettus aegyptiacus). 2. Genomic DNA, isolated from the fibroblast cells, was restriction digested and probed for the 9-kDa calbindin gene with a 180 base pair fragment of mouse calbindin-D9K cDNA. Genomic DNA from rats and humans was similarly probed. 3. Hybridization and thus homology was observed between the mouse probe and DNA from the rat and the fruit bat, but not the human. 4. The results are discussed in relation to the detection of calbindin-D9K in the fruit bat despite very low circulating levels of its inducer 1,25(OH)2D3. PMID- 8482082 TI - Treatment strategies for patients with the Guillain-Barre syndrome. PMID- 8482083 TI - Pulmonary microvascular fat in lung injury: an epiphenomenon? PMID- 8482084 TI - Pharmacokinetics of catecholamines in critically ill children: "you pays your money and you takes your choice". PMID- 8482085 TI - Severity of illness scoring: East meets West. PMID- 8482086 TI - Plasma exchange morbidity in Guillain-Barre syndrome: results from the French prospective, randomized, multicenter study. The French Cooperative Group. AB - OBJECTIVES: To describe all adverse events occurring during plasma exchange sessions in adult patients with the Guillain-Barre syndrome. To analyze these events with regard to the technical modalities and biological changes induced by sessions, and to try to identify a population at high risk for adverse events. DESIGN: Double-blind, randomized, prospective, multicenter trial. SETTING: A total of 28 French and Swiss intensive care units. PATIENTS: The study is based on 220 patients allocated either to plasma exchange (n = 109) or not (n = 111). This study focused on 105 patients who received at least one plasma exchange, with replacement fluid secondly allocated by randomization to albumin, or fresh frozen plasma. A total of 105 patients underwent 390 plasma exchanges. Fifty-five patients received albumin (208 sessions) as replacement fluid, and 50 patients received fresh frozen plasma (182 sessions). INTERVENTIONS: Prospective monitoring of patients for each session including technical modalities, adverse effects, and biological parameters. MEASUREMENTS AND MAIN RESULTS: A total of 253 adverse incidents were recorded. At least one adverse incident occurred in 39% of plasma exchange sessions among 80 (76%) patients. In 15 patients, plasma exchange treatment had to be discontinued because of severe intolerance (six patients, including three patients with severe bradycardias), intercurrent complications, mainly infections (four patients), and technical difficulties. One patient with pneumococcal septicemia and pneumonia died during the second plasma exchange session. Fresh frozen plasma was associated with more adverse incidents than albumin (135 vs. 118, p = .008). The occurrence of adverse events was also related to the preplasma exchange hemoglobin level assessed before the session (p = .04). Otherwise, the frequency of adverse effects did not depend on technical modalities (type of equipment, anticoagulation). Age, sex, previous history, neurologic severity, and the need for mechanical ventilation, as assessed on inclusion in the study, did not modify the risk of adverse effects. Finally, occurrence of bradycardia did not rely on initial neurologic severity. CONCLUSIONS: These results confirm that fresh frozen plasma should be abandoned as replacement fluid in plasma exchanges of Guillain-Barre syndrome patients. They also underline the need for close monitoring of patients during sessions and, especially, the respect of treatment contraindications. Some adverse incidents could be attributed to the underlying disease rather than to the plasma exchange session. PMID- 8482087 TI - Pulmonary microvascular fat: the significance? AB - OBJECTIVE: To determine the effects of fat emboli on cardiopulmonary function in critically ill patients. DESIGN: A prospective study. SETTING: Tertiary referral medical/surgical shock/trauma intensive care unit (ICU). PATIENTS: A total of 51 critically ill medical and surgical (including acute trauma) patients who required supplemental oxygen (FIO2 of > or = 0.35) to maintain arterial blood oxyhemoglobin saturation of > or = 90% and who had 62 pulmonary artery catheters placed for patient care reasons. INTERVENTIONS: Pulmonary capillary blood samples were obtained via the pulmonary artery catheters in the "wedged position" at insertion and postinsertion at 8, 24, 48, and 72 hrs. Cytospun smears of the buffy coat aspirates of these samples were made and were stained with Oil Red-O for fat. MEASUREMENTS AND MAIN RESULTS: One investigator, without knowledge of the patients' cardiopulmonary function, examined all smears and graded them 0 to 4+ for amount of fat. Fat scores were correlated with chest radiograph appearance, hemodynamic and respiratory parameters, complete blood cell counts with differential white blood cell counts, whether the patient was receiving lipid-containing parenteral nutrition, principal organ system failure, and reason for ICU admission. Samples from 27 pulmonary artery catheter insertions had no fat, 13 samples had low-grade (1+) episodic fat, and 22 samples had repeated episodes of > or = 2+ fat or isolated episodes of 4+ fat. There was a significant association between the amount of pulmonary microvascular fat and trauma as the reason for ICU admission. Of the other parameters, only chest compliance and body temperature showed unequivocal significant associations. These associations were opposite to the expected findings, but would support a conclusion that fat emboli did not cause the observed cardiopulmonary dysfunction. The inconsistent associations for the FIO2, PCO2, and mixed venous blood oxyhemoglobin saturation may be random events. CONCLUSION: Cardiopulmonary dysfunction commonly attributed to fat emboli is likely due to other causes. PMID- 8482088 TI - Dobutamine infusions in stable, critically ill children: pharmacokinetics and hemodynamic actions. AB - OBJECTIVE: To delineate dobutamine pharmacokinetics and hemodynamic responses in children. DESIGN: Prospective, pharmacokinetic study using sequential, graded dosing of drug. INTERVENTIONS: Graded intravenous dobutamine infusions of 0.5, 2.5, 5, 10, and 20 micrograms/kg/min were sequentially administered for 25 mins each. Plasma dobutamine concentrations and echocardiographically determined hemodynamic data were obtained at baseline and at 15 and 25 mins during each infusion rate. Hemodynamic responses were evaluated by paired t-test and by computerized evaluation of individual dose-response curves. SETTING: Pediatric intensive care unit in a university setting. PATIENTS: Eleven stable, critically ill children previously requiring inotropic support with dobutamine. Seven patients were postcardiac surgical patients; four patients had acute cardiac dysfunction with septic shock and/or adult respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Mean cardiac index increased from 3.8 to 5.2 L/min/m2 (p < .05). Increasing the infusion rate from 10 to 20 micrograms/kg/min increased cardiac index by 16% (p < .05). Cardiac index increased by > 10% in four of seven patients at a dobutamine infusion rate of 0.5 microgram/kg/min (mean 21%). The relationship of plasma dobutamine concentration to cardiac index, systolic blood pressure, and heart rate fit a threshold model with a log-linear relationship after the threshold in seven of nine, seven of 11, and eight of 11 patients, respectively. As anticipated, in the patients who responded, there were linear increases in hemodynamic responses with exponential increases in plasma dobutamine concentrations. Mean plasma clearance rate was 82 +/- 3 mL/min/kg. First-order kinetics were demonstrated by the direct linear relationship of plasma dobutamine concentration to infusion rate (mean r2 = .95; p < .01 for each patient) and by independence of clearance from dose and duration of each infusion. CONCLUSIONS: Dobutamine effectively improves systolic function in critically ill children. Hemodynamic responses to dobutamine generally follow a predicted log-linear dose-response model. Dobutamine clearance in this study was consistent with first-order kinetics. The wide variability in hemodynamic responses and clearance kinetics indicate that dobutamine infusions must be titrated individually. PMID- 8482089 TI - One-year outcome of elderly and young patients admitted to intensive care units. AB - OBJECTIVE: To compare the outcome of patients over and under age 65 admitted to two intensive care units (ICUs). DESIGN: Prospective, two-center study. Convenience sample of all admissions to two adult ICUs for a 1-yr period, with a 1-yr follow-up. SETTING: Adult multidisciplinary closed ICUs. PATIENTS: All patients (n = 1,040) admitted to two ICUs during a 1-yr period were entered into the study, except patients with self-induced poisoning. Of these patients, 145 patients were lost to follow-up. INTERVENTIONS: Admission statistics on all patients included demographic, case mix, and severity data. Variables associated with intensive care unit outcomes at discharge (length of stay, mortality) and at 1 yr from admission (mortality, functional capacity, health attitudes) were analyzed. Vital status was confirmed from both Alberta Vital Statistics and Alberta Health. Follow-up interviews were conducted with all available survivors. RESULTS: The elderly group (> 65 yrs) comprised 46% of patients studied. Both age groups (> 65 yrs and < 65 yrs) had comparable demographics and illness severity measures. Although ICU and 1-yr mortality rates differed between groups (16% of > 65 yrs vs. 12.9% of < 65 yrs ICU mortality and 49% of > 65 yrs vs. 31% of < 65 yrs 1-yr mortality), age was not a major contributor to the variance in outcome. At 1 yr, 65% of patients admitted to the study were alive. Follow-up interviews were conducted with 75% of survivors. Assessment of activities of daily living showed that the elderly patients were similar to younger patients. The elderly demonstrated more positive health attitudes than younger survivors. Functional capacity was significantly associated with health attitudes of younger patients, but not for older survivors. CONCLUSIONS: Age does not have an important impact on outcome from critical illness, which is most strongly predicted by severity of illness, length of stay, prior ICU admission and respiratory failure. Satisfaction with personal health should not be inferred from the functional status of elderly survivors of intensive care. PMID- 8482090 TI - Functional responses to extremely high plasma epinephrine concentrations in cardiac arrest. AB - OBJECTIVE: To evaluate the action of high-dose epinephrine by measuring simultaneously its vasopressor and norepinephrine releasing effects in humans during cardiac arrest. DESIGN: A prospective study on consecutive patients admitted with cardiac arrest. SETTING: Emergency Department in a large, urban hospital. PATIENTS: Eighteen patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (CPR). INTERVENTIONS: Catheterization of both the aorta and right atrium for the recording of pressure and collection of blood samples. Throughout the study period (12.5 mins), 18 patients received epinephrine at both the standard dose (1 mg, approximately 0.015 mg/kg) and high dose (0.2 mg/kg). Blood samples were drawn five times, every 2.5 mins. MEASUREMENTS AND MAIN RESULTS: Plasma epinephrine and norepinephrine concentrations; aorta, right atrial, and coronary perfusion pressures. Epinephrine concentrations (normal at rest = 160 +/- 10 [SEM] pmol/L) were increased at the time of the first sample (2.5 mins) by approximately 3,000-fold (to approximately 0.5 mumol/L), and, increased further to 12,000-fold (approximately 2.0 mumol/L) during the study. Aortic pressure increased from 20 +/- 3 to 28 +/- 3 mm Hg (p < .001), and coronary perfusion pressure increased from 4 +/- 3 to 10 +/- 3 mm Hg (p < .001). Simultaneous plasma norepinephrine concentrations were 30-fold higher than the normal resting value of 1.30 +/- 0.04 nmol/L, and increased by 90-fold during the study (p < .001). The spectral distributions of the individual correlations between plasma epinephrine and norepinephrine concentrations were segregated into high correlations (r > .83) in 12 of 18 patients and low r values (r = .29 to .79) in the remaining six patients. The distribution of the correlations was nonuniform by the Kolmogorov Smirnov goodness-of-fit test with p < .001; this profile suggests that norepinephrine responsiveness to epinephrine can separate two populations, one of which (r > .83) would have preserved viability of the corresponding epinephrine receptors. The correlations between plasma epinephrine concentrations and coronary perfusion pressures were distributed more evenly, also in a nonuniform pattern (p < .02 by Kolmogorov-Smirnov goodness-of-fit test) and the relationship between the two sets of correlations was not significant. CONCLUSIONS: Despite the very high prevailing plasma epinephrine concentrations during cardiac arrest, further epinephrine increases still elicit biological responses. The present work provides physiologic support for the use of large doses of epinephrine during the course of CPR. PMID- 8482091 TI - Verification of the Acute Physiology and Chronic Health Evaluation scoring system in a Hong Kong intensive care unit. AB - OBJECTIVES: To validate the Acute Physiology and Chronic Health Evaluation (APACHE II) severity of illness scoring system in Chinese patients in a multidisciplinary intensive care unit (ICU) in Hong Kong. To audit the service and utilization of an ICU with a low ICU to hospital bed ratio. DESIGN: Prospective data collection and review. SETTING: A 12-bed multidisciplinary ICU within a 1,430-bed tertiary care university hospital. PATIENTS: Data from 1,573 of 1,814 consecutive patients admitted to the ICU from May 1988 to November 1990 were studied. The patients were all Chinese. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patients' clinical details and APACHE II scores were recorded on day 2 of admission and reviewed at hospital discharge or after death. The APACHE II scores, risk of death values, age, and length of ICU stay between survivors and nonsurvivors were compared by two-sample t-tests. Relationships between mortality and APACHE II score, risk of death, and results from previous studies were investigated using the Pearson product-moment coefficient and regression analysis. Predictive capacity of risk of death was assessed by receiver operating characteristic curve analysis. The hospital mortality rate for study patients was 36%. Survivors were younger, had shorter ICU stays, lower APACHE scores, and lower risk of death values than nonsurvivors (p < .001). There was close correlation (r2 = .81, .77, and .76 for all patients, operative group, nonoperative group, respectively) between APACHE II scores and predicted risk of death values. Risk of death was an accurate group predictor of death in all patients and in separate operative and nonoperative groups. Areas under the receiver operating characteristic curves were 0.89 (all patients), 0.85 (operative), and 0.88 (nonoperative). Neither the Apache II scores nor risk of death scores were sufficiently accurate to predict outcome of individual patients. There was close concordance between observed and predicted mortality of patient groups. Mortality ratio was 0.97 (all patients), 0.89 (operative group), and 1.02 (nonoperative group). Chronological age, per se, was not a good predictor of mortality. The audit of the ICU service showed a short length (4.2 days) of ICU stay and high bed occupancy (80%). Subgroups of low-risk, postoperative patients with good outcomes and poor-risk patients admitted after cardiopulmonary arrest with a high mortality rate were identified. CONCLUSIONS: The APACHE II scoring system was an accurate predictor of group outcome in a Chinese population, making it suitable for comparisons between countries. Application of the APACHE II scoring system in a clinical audit facilitates critical appraisal of an ICU service. Problems identified by the study were a shortage of ICU beds and delayed referrals of patients. PMID- 8482092 TI - Coagulopathy as a predictor of outcome in meningococcal sepsis and the systemic inflammatory response syndrome with purpura. AB - OBJECTIVE: To identify simple, contemporary predictors of both morbidity and mortality in pediatric patients with purpuric sepsis syndrome in order to provide a basis for future study of innovative interventions. DESIGN: Retrospective study. SETTING: An 18-bed multidisciplinary intensive care unit (ICU) in a large pediatric hospital. PATIENTS: A total of 53 patients, ranging in age from 18 days to 17 yrs (mean 4.9 yrs) with either culture-proven meningococcal sepsis or the systemic inflammatory response syndrome with purpura, who were admitted to the ICU during the period from January 1, 1982 through March 15, 1992. METHODS: A computerized database was constructed containing the characteristics of these patients at presentation, during the first 24 hrs of hospitalization, and on discharge. Single variables were screened for significance between "good" (intact survival) and "poor" (mortality or survival with significant morbidity) outcome groups. Those variables found to be most significant were then tested for sensitivity, specificity, and predictive value. The best predictors identified in this manner were then compared with the two most-cited prognosticating strategies as applied to these patients. MEASUREMENTS AND MAIN RESULTS: Coagulopathy (defined as a partial thromboplastin time > 50 secs or serum fibrinogen concentration < 150 mg/dL [4.4 mumol/L]) at the referral site or on ICU admission was identified as an excellent predictor of poor outcome: sensitivity, specificity, positive and negative predictive values of a low serum fibrinogen value, being 81%, 95%, 93%, and 88%, and of prolonged partial thromboplastin time, being 95%, 90%, 86%, and 97%, respectively. Classical prognosticating strategies were found to be inadequately associated with mortality, yet comparable with coagulopathy in identifying patients destined for clinically important morbidity. CONCLUSIONS: We conclude that: a) outcome of pediatric patients with meningococcal sepsis or the systemic inflammatory response syndrome with purpura can be predicted rapidly, more easily, and with overall accuracy superior to classical prognostication strategies by the simple presence or absence of coagulopathy; b) when applied to a contemporary population, classical prognostication strategies lack value for prediction of mortality, yet remain valid for prediction of "poor outcome" (significant morbidity + mortality); c) when evaluating treatment strategies for such patients, the presence of serious coagulopathy may potentially be useful as an index of illness severity. PMID- 8482093 TI - Effects of pentoxifylline on in vivo leukocyte function and clearance of group B streptococci from preterm rabbit lungs. AB - OBJECTIVES: Pentoxifylline was evaluated for its ability to enhance inactivation of group B streptococci in lungs of prematurely born rabbits. Mechanisms associated with intrapulmonary streptococcal clearance and the pharmacodynamics of pentoxifylline were also investigated. DESIGN: Randomized, controlled animal trial. SETTING: University research laboratory. SUBJECTS: A total of 123 New Zealand rabbits were delivered prematurely by cesarean section and were used for clearance studies. Twenty-three preterm pups were additionally utilized to study the pharmacodynamics of pentoxifylline. INTERVENTIONS: Preterm rabbits were infected with group B streptococcal aerosols and given intraperitoneal injections of either pentoxifylline (25, 12.5, and 12.5 mg/kg) or placebo at 0, 6, and 12 hrs after infection. MEASUREMENTS AND MAIN RESULTS: At 0, 4, and 24 hrs, the numbers of streptococci were determined in the left lung, while the right lung underwent bronchoalveolar lavage to quantify intra-alveolar leukocytes, phagocytosis of inhaled bacteria, and concentrations of lysozyme and tumor necrosis factor. In a separate experiment, blood and bronchoalveolar fluid from infected animals were analyzed for pentoxifylline content. Streptococcal proliferation was less in pentoxifylline-treated animals than in controls at 24 hrs (p < .01). Pulmonary macrophages and polymorphonuclear leukocytes recovered from bronchoalveolar lavage fluid did not differ in numbers or phagocytic activity. Pentoxifylline-treated animals had lower levels of lysozyme (p < .02) and tumor necrosis factor (p < .005) in bronchoalveolar lavage fluid compared with placebo-treated pups. Therapeutic levels of pentoxifylline were achieved in blood and bronchoalveolar lavage fluid. CONCLUSIONS: Despite lowering lysozyme and tumor necrosis factor content in epithelial lining fluid, pentoxifylline improves the inactivation of group B streptococci in preterm rabbit lungs. These findings suggest that increased group B streptococcal clearance was coincident with an anti-inflammatory effect due to pentoxifylline. We conclude pentoxifylline may be clinically useful as an adjunctive therapy for group B streptococcal pneumonia in newborns. PMID- 8482094 TI - Collateral perfusion through overlapping vessels reduces canine right ventricular ischemic injury from positive end-expiratory pressure. AB - OBJECTIVE: To test, in a canine model of right ventricular ischemia with 15 cm H2O positive end-expiratory pressure, whether collateral perfusion through overlapping vessels from the left ventricle to the right ventricular free wall can reduce infarct size. DESIGN: Randomized, prospective, controlled, experimental study in dogs. SETTING: Anesthesia research laboratory of an academic medical center. SUBJECTS: Twenty microfilaria-free mongrel dogs. INTERVENTIONS: Anesthetized, closed-chest dogs were managed with the application of 15 cm H2O positive end-expiratory pressure. The right coronary artery was ligated (90 mins) with occlusion (n = 10) and without occlusion (n = 10) of overlapping vessels. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow (using radioactive microspheres) was measured in the area at risk (gentian violet) and in the area of necrosis (triphenyltetrazolium chloride). With right coronary and overlapping vessel occlusion, blood flow in the area at risk decreased from 80.1 +/- 14.0 to 9.0 +/- 1.7 mL/min/100 g after 5 mins of ischemia (p = .0001) and remained depressed at 8.7 +/- 1.8 mL/min/100 g after 75 mins of ischemia. With right coronary occlusion alone, blood flow decreased after 5 mins of ischemia from 64.8 +/- 5.4 to 14.3 +/- 1.9 mL/min/100 g (p = .0001 compared with baseline), which was 60% greater than the group with occluded collateral vessels (p = .0055). Moreover, after 75 mins of ischemia, blood flow in the area at risk increased further to 28.9 +/- 5.4 mL/min/100 g with patent overlapping vessels (p = .0001 compared with 5-min value). The patency of overlapping vessels during right ventricular free wall ischemia reduced the area at risk from 68.5 +/- 2.4% to 38.6 +/- 5.1% (p = .0001) and the area of necrosis/area at risk from 58.1 +/- 8.4% to 16.9 +/- 3.6% (p = .0007). CONCLUSIONS: Despite 15 cm H2O positive end expiratory pressure, perfusion through overlapping vessels improved peri-ischemic blood flow in the area at risk, thereby reducing the size of the risk area and the amount of right ventricular free wall necrosis. PMID- 8482095 TI - Action of carbon dioxide on hypoxic pulmonary vasoconstriction in the rat lung: evidence against specific endothelium-derived relaxing factor-mediated vasodilation. AB - OBJECTIVES: The effect of hypercapnia on pulmonary vascular tone is controversial with evidence for both a vasoconstrictor and vasodilator action. The objective of this study was to investigate the possibility that this dual response to CO2 could be explained by a direct constrictor action on smooth muscle and an indirect dilator action via the release of endothelium-derived relaxing factor. The effect of ventilation with hypercapnia (FICO2 0.15) on pulmonary pressor response to hypoxia (FIO2 0.3) was investigated. DESIGN: Prospective, randomized study. SETTING: The National Heart and Lung Institute, UK. SUBJECTS: The isolated, blood-perfused rat lung. INTERVENTIONS: Angiotensin-II and a blocker of endothelium-derived relaxing factor synthesis, NG-monomethyl-L-arginine (L-NMMA). MEASUREMENTS AND MAIN RESULTS: The vasomotor effect of hypercapnia depended on pulmonary arterial pressure. Under resting tone, CO2 acted as a mild constrictor (change in mean pulmonary arterial pressure from 14 +/- 2 to 15 +/- 2 mm Hg, n = 4; p < .05. At increased tone, induced either by hypoxia or Angiotensin-II, CO2 was a vasodilator. Thus, hypoxia increased mean pulmonary arterial pressure from 17 +/- 2 to 32 +/- 2 mm Hg (n = 8; p < .01), but simultaneous ventilation with hypoxia and hypercapnia reduced this by 16 +/- 1% (p < .01). Angiotensin-II (1 microgram) increased pulmonary arterial pressure from 14 +/- 2 to 39 +/- 5 mm Hg (n = 8; p < .01), but with hypercapnia, this angiotensin-induced pulmonary vasoconstriction was reduced by 18 +/- 6% (p < .001). The reduction in hypoxic pulmonary vasoconstriction induced by hypercapnia was not significantly different from that seen with Angiotensin-II hypercapnia. Blocking endothelium-derived relaxing factor synthesis using 30 microM NG-monomethyl-L-arginine did not significantly change either basal pulmonary arterial pressure or the response to hypercapnia, but increased hypoxic pulmonary vasoconstrictor by 24 +/- 4% (n = 4; p < .01). There was no significant difference between the change in hypoxic pulmonary vasoconstriction induced by hypercapnia after saline control (21 +/- 8% decrease) and the change in hypoxic pulmonary vasoconstriction caused by CO2 after 30 microM L-NMMA (25 +/- 10% decrease, p < .05, n = 8). CONCLUSION: Endothelium-derived relaxing factor seems unlikely to specifically modulate CO2 induced vasodilation in the rat pulmonary circulation. PMID- 8482096 TI - Pulmonary venodilation by isoflurane improves gas exchange during Escherichia coli bacteremia. AB - OBJECTIVE: To determine how isoflurance affects the longitudinal distribution of pulmonary vascular resistance and pulmonary gas exchange during Escherichia coli bacteremia. DESIGN: Prospective, controlled study with open-label assignment of animals to two groups. SETTING: Laboratory. SUBJECTS: Goehingen minipigs. INTERVENTIONS: Induction of acute respiratory failure by a 4-hr infusion of live E. coli bacteria in 12 animals; six animals anesthetized with methohexital/piritramide; six animals anesthetized with isoflurane. The control group consisted of four animals that received the same surgical procedure, but no E. coli infusion. Two animals were anesthetized with methohexital/piritramide and two with isoflurane, respectively. MEASUREMENTS AND MAIN RESULTS: Cardiac output and pressures were measured by means of an arterial catheter, Swan-Ganz catheter, and a left atrial catheter. Effective pulmonary capillary pressure was evaluated graphically from a pulmonary artery occlusion pressure decay. Arterial-alveolar PO2 ratio was calculated to evaluate pulmonary function. Measurements were performed before and after 1, 2, and 3.5 hrs of E. coli infusion. Statistical significance was tested with analysis of variance (ANOVA). E. coli infusion caused hypodynamic shock, an increase in pre- and postcapillary pulmonary vascular resistance and respiratory failure. Postcapillary pressure gradient and effective pulmonary capillary pressure were lower in the isoflurane-group. Methohexital-anesthetized animals developed pulmonary dysfunction after 1 hr of bacteremia, whereas isoflurane-anesthetized animals developed pulmonary dysfunction after 3.5 hrs of E. coli infusion (significantly different, ANOVA, p < .05). There were no significant changes in the sham group. CONCLUSIONS: Isoflurane is a pulmonary venodilator. During lethal E. coli infusion, it ameliorates the increase in pulmonary capillary pressure and preserves pulmonary function until vascular permeability increases. PMID- 8482097 TI - Diphosphoryl lipid A from Rhodopseudomonas sphaeroides induces tolerance to endotoxic shock in the rat. AB - OBJECTIVES: To examine the hemodynamic effects of diphosphoryl lipid A from Rhodopseudomonas sphaeroides and to examine the ability of this substance to induce tolerance to endotoxic shock. DESIGN: Randomized, prospective, controlled study comparing the hemodynamic actions of R. sphaeroides diphosphoryl lipid A to those effects of lipopolysaccharide form Salmonella minnesota, followed by a prospective, randomized, controlled study comparing pretreatment with R. sphaeroides diphosphoryl lipid A and phosphate-buffered saline in the induction of tolerance to endotoxic shock. SETTING: Laboratory of the Section of Critical Care Medicine at a University Hospital. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Eight rats were randomized to receive intravenous R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight or S. minnesota lipopolysaccharide, 0.5 mg/100 g body weight. Ten rats were then randomized to receive R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight, or phosphate-buffered saline intravenously 48 hrs before receiving S. minnesota lipopolysaccharide, 5 mg/100 g body weight, by intravenous infusion. MEASUREMENTS AND MAIN RESULTS: Cardiac index was significantly decreased from baseline in rats treated with lipopolysaccharide; there was no significant change in the R. sphaeroides diphosphoryl lipid A group. Peak circulating tumor necrosis factor (TNF) concentrations in the lipopolysaccharide-treated rats were higher than in R. sphaeroides diphosphoryl lipid A-treated rats (3.1 +/- 1.0 vs. 1.5 +/- 0.4 ng/mL). R. sphaeroides diphosphoryl lipid A significantly attenuated lipopolysaccharide-induced changes in mean arterial pressure and cardiac index. At baseline, there was no significant difference in serum TNF concentrations between rats pretreated with R. sphaeroides diphosphoryl lipid A and those rats pretreated with phosphate-buffered saline. TNF levels peaked at 1 hr post lipopolysaccharide infusion at 4.3 +/- 0.6 ng/mL in the phosphate-buffered saline group and at 2.0 +/- 0.5 ng/mL in the R. sphaeroides diphosphoryl lipid A group (p < .02). Four of five rats pretreated with R. sphaeroides diphosphoryl lipid A survived endotoxic shock, whereas none of the phosphate-buffered saline pretreated rats survived (p = .05). CONCLUSIONS: These observations are consistent with previous reports of the limited toxic effects of R. sphaeroides diphosphoryl lipid A and suggest that this molecule retains the ability to induce tolerance to endotoxic shock. PMID- 8482098 TI - Role of nitric oxide in the hemodynamic changes of sepsis. AB - OBJECTIVE: To study the role of nitric oxide in the hemodynamic changes of sepsis. DESIGN: Prospective, randomized, controlled, intervention study. SUBJECTS: Twenty-five sheep randomized to four groups: Group A (n = 8, nonseptic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) followed 15 mins later by L arginine (200 mg/kg i.v.); group B (n = 4, nonseptic sheep) received L-arginine followed 15 mins later by NG-nitro L-arginine; group C (n = 7, septic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) alone; group D (n = 6, septic sheep) received L-arginine (200 mg/kg i.v.) followed by NG-nitro L-arginine (20 mg/kg i.v.). INTERVENTIONS: Sheep were anesthetized with pentobarbital, mechanically ventilated and monitored with a pulmonary artery catheter, a peripheral artery catheter, and a Miller catheter in the left ventricle. Sepsis was induced by the intravenous administration of live Escherichia coli (1.5 x 10(9) microorganisms/kg over 30 mins), which resulted in systemic hypotension, pulmonary hypertension, high cardiac output, and hyperlactatemia. Acetylcholine was administered before and after each intervention. MEASUREMENTS AND MAIN RESULTS: In nonseptic sheep (groups A and B) NG-nitro L-arginine induced an increase in mean blood pressure (BP), pulmonary arterial pressure, and systemic and pulmonary vascular resistances, accompanied by a decrease in cardiac index and the first derivative of left ventricular pressure. L-arginine administered to normal sheep induced systemic vasodilation. In the sepsis groups (groups C and D), the increases in BP and systemic vascular resistances induced by NG-nitro L arginine were significant but less marked than in nonseptic sheep. Pretreatment of septic sheep with L-arginine totally abolished the NG-nitro L-arginine induced increases in systemic and pulmonary vascular resistances in this group. The administration of L-arginine in these animals induced both systemic and pulmonary vasodilation. Acetylcholine-mediated vasodilation was severely impaired in sepsis. In this condition, pretreatment with L-arginine improved the response to acetylcholine. CONCLUSIONS: These data support the view that nitric oxide plays a significant role in modulating systemic and pulmonary vasomotor tone in normal and septic sheep. L-arginine produced systemic vasodilation in normal sheep, whereas both systemic and pulmonary vasodilation were observed in septic animals. The impaired response to an endothelium-dependent vasodilator in sepsis was improved by the previous administration of L-arginine. PMID- 8482099 TI - Lung lavage with oxygenated perfluorochemical liquid in acute lung injury. AB - OBJECTIVE: To investigate the effects of lung lavage with oxygenated liquid perfluorochemical on gas exchange, lung mechanics, and cardiac function in animals with acute lung injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory. SUBJECTS: Eight adult cats (2 to 4 kg, random sex). INTERVENTIONS: Two insults were combined to cause lung injury: oleic acid infusion and saline whole-lung wash. Animals were assigned to either the control or treatment group which consisted of a perfluorochemical liquid (Rimar 101) lavage. Perfluorochemical liquid lavage was performed three times at hourly intervals after lung injury. Three other cats with identical injury but no perfluorochemical liquid lavage served as control animals. All cats were ventilated with an FIO2 of 0.95 and positive end-expiratory pressure of 2 cm H2O continuously. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas tensions and pH, dynamic pulmonary compliance were measured at 15-min intervals. Cardiac index was assessed hourly, and lung fluid was collected after each of the three perfluorochemical liquid lavages. Arterial oxygen tension and pulmonary compliance deteriorated abruptly after lung injury in all cats, and improved significantly (p < .001, two-way analysis of variance) 15 mins after perfluorochemical liquid lavage. These parameters gradually returned to their baseline over 60 mins. Arterial blood pressure and cardiac index decreased after injury in all cats, and were not significantly changed after perfluorochemical liquid lavage. Hemorrhagic fluid was recovered from distal airways by perfluorochemical liquid lavage, despite prior suctioning of the airway. CONCLUSIONS: Perfluorochemical liquid lavage removes pulmonary edema fluid and improves gas exchange and the mechanical properties of the lung, after acute severe lung injury. PMID- 8482100 TI - Pediatric intensive care training: confronting the dark side. AB - PURPOSE: To describe the dark side of pediatric intensive care fellowship training and offer educational approaches for understanding feelings of fallibility, anger, frustration, and loss. DATA SOURCES: Listening and observing fellows in the courses of their pediatric intensive care training and later careers. STUDY SELECTION: Studies that discussed pediatric residency and fellowship training, especially in the context of intensive care. DATA EXTRACTION: From group meetings, unit conferences, rounds, individual discussions, and child psychiatric consultations. RESULTS OF DATA SYNTHESIS: Pediatric intensive care unit (ICU) fellows gain a sense of mastery from the nature of their work: complex, technological, and frequently lifesaving. They face the usual personal stresses of extended training, including long work hours, limited financial resources, and relative isolation from family and friends. Pediatric ICU fellows confront deeper, "dark" feelings regarding their own high expectations, fallibility, anger, sense of loss, frustration, limited control, and the need to work closely with tense, grieving families. If the dark side is not acknowledged, fellows, team members, and faculty are likely to experience anger, detachment, and depression that may extend beyond work into their personal lives. CONCLUSIONS: Since the dark side is expected, normal, and inevitable, fellowship training programs should help fellows cope with and understand these feelings. Such understanding requires a sense of trust among intensive care staff and can be gained through group discussions, mentorship, specific team conferences, and child psychiatric consultation. PMID- 8482101 TI - Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. AB - OBJECTIVES: To review the molecular pathogenesis of septic shock, with particular emphasis on the induction of cytokines by endotoxin. By understanding the mechanisms that result in the systemic inflammatory response, novel clinical interventions may be more effectively studied. DATA SOURCES: The English medical literature was reviewed, including human clinical trials, animal experiments, and in vitro studies elucidating cellular and molecular interactions. Expert testimony from the Roundtable Conference on Sepsis (Brussels, March 1992) was also used to synthesize emerging concepts and to ensure inclusion of ongoing investigations. STUDY SELECTION: Emphasis on controlled experimental studies which elucidated the molecular and cellular interactions during sepsis. DATA EXTRACTION: This study focused only on data that directly involved the induction and regulation of protein mediators of sepsis, especially tumor necrosis factor (TNF) and interleukin-1. Data concerning the role of TNF during health were extracted from the author's peer-reviewed data. DATA SYNTHESIS: Information concerning the many facets of the systemic inflammatory response was integrated into a chronological, clinically oriented model of cytokine induction during endotoxemia. CONCLUSIONS: The induction of inflammation during sepsis is a complex, but increasingly understood, biological cascade that is dependent on inter- and intracellular signaling. Novel biotherapies may improve patient outcome in sepsis by interrupting any or all points of signal transduction. PMID- 8482102 TI - Detection of unsuspected imposed work of breathing: case reports. PMID- 8482103 TI - Hemodynamic changes and circulating recombinant tumor necrosis factor-alpha concentrations in a patient undergoing isolated limb perfusion. PMID- 8482104 TI - Dopamine infused continuously at high concentration with a low flow rate affects arterial blood pressure fluctuation waves. PMID- 8482105 TI - The case for standardized terminology: oxygen "saturation" values can trick the unwary and lead to clinical misjudgment. PMID- 8482106 TI - Anion gap, lactate, and acid-base status after cardiac surgery. PMID- 8482107 TI - Definitions for sepsis and organ failure. PMID- 8482108 TI - Clinical use of pulmonary capillary pressure: a technique whose time has arrived. PMID- 8482109 TI - Retinal pigment epithelial cells produce interleukin-1 beta and granulocyte macrophage colony-stimulating factor in response to interleukin-1 alpha. AB - The retinal pigment epithelium (RPE) is clinically involved in diverse ocular inflammatory diseases. Because perturbed RPE cells produce a variety of inflammatory substances, RPE cells may play an integral part in these diseases. Interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM CSF) are pleiotropic cytokines with the ability to trigger numerous inflammatory responses. This report shows that cultured human RPE cells synthesize interleukin 1 beta (IL-1 beta) and GM-CSF in response to the potentially inflammatory cytokine, IL-1 alpha, but not to E. coli endotoxin. Control RPE cells made little or no mRNA or protein for either IL-1 beta or GM-CSF. Upon stimulation of the cells by IL-1 alpha, both IL-1 beta and GM-CSF mRNAs were readily apparent by 3 hours, persisted for over 24 hours, and were translated into immunologically detectable proteins. GM-CSF protein was secreted into the culture medium, whereas IL-1 beta protein remained cell associated. The IL-1 alpha-induced mRNA and protein production were inhibited by dexamethasone. These observations provide additional evidence that RPE cells are capable of playing a pivotal role during ocular inflammation. PMID- 8482110 TI - Reduction in choroidal blood flow occurs in chicks wearing goggles that induce eye growth toward myopia. AB - Goggles that degrade the retinal image produce axial enlargement of the ocular globe and large myopic refractive errors. Many authors have assumed that visual image degradation itself leads to myopia. Hodos and co-authors have shown, however, that goggled eyes in chicks are considerably warmer than normal. Such temperature changes may either underlie or be a consequence of alterations in choroidal blood flow (CBF). Since alterations in CBF could affect eye growth, we explored the effect of monocular goggling on CBF in chicks. Plastic goggles were glued over one eye in four-day old chicks and the goggles were left in place for 12 or 14 days. Fourteen days after the goggling, CBF was measured using laser Doppler velocimetry. Three groups of chicks were studied: 1) chicks with goggles for 14 days; 2) chicks with goggles for 12 days followed by no goggles for the two days; 3) age matched non-goggled chicks. A -scan ultrasonography confirmed that the visual deprivation produced vitreous chamber elongation in the goggled eye and that the degree of elongation for the goggled eye was the same for the two goggled groups. The results were: 1) blood flow in non-goggled chicks was similar in both eyes; 2) blood flow was significantly reduced in the goggled eye in chicks wearing goggles for 14 days- 37% of control; and 3) blood flow was still significantly reduced in the goggled eye in chicks whose goggles were removed two days before measurement- 51% of control. These results show that CBF is reduced by goggles that result in myopic eye growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482111 TI - Choroidal blood flow is reduced in chicks with ocular enlargement induced by corneal incisions. AB - We have previously reported decreased choroidal blood flow (CBF) associated with goggle-induced ocular enlargement and myopia. It was uncertain, however, if this change in CBF was related to the occurrence of ocular enlargement or the increased ocular temperature produced by the goggle. We therefore used corneal surgery-induced ocular enlargement that eliminated the thermal effects observed with goggles to investigate the effects of ocular enlargement on CBF. Central corneal incisions (2 mm in length) were made in the right eye of 4 day old chicks and the wound sutured. In one group, the incision was oriented along the vertical meridian (with the head in its natural position -beak tip 30-45 degrees below horizontal), while in another group the incision was oriented along the horizontal meridian (with the head in its natural position). Age matched controls received no corneal incision. Two weeks later, CBF was measured using laser Doppler velocimetry. After determining CBF, the eyes were removed and axial length, nasotemporal length and dorsoventral length were measured. Ocular enlargement was induced in 11 out of 12 chicks with vertical cuts. The CBF in the operated eye of these 11 animals was 62% of that in the nonoperated eye. Ocular enlargement was also induced in eight of 14 chicks with horizontal cuts. The CBF in the operated eye in these eight chicks was 60% of that in the nonoperated eye. The extent of eye growth was greater in all dimensions in the vertical cut chicks with ocular enlargement than in the horizontal cut chicks with ocular enlargement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482112 TI - Human retinoblastoma cells express alpha B-crystallin in vivo and in vitro. AB - alpha B-crystallin is a major lens protein that is a member of the heat-shock family of proteins. Using immunohistochemical and northern blot techniques, we now demonstrate its presence in freshly-fixed retinoblastoma tissue. The protein is also abundantly expressed in cultured human retinoblastoma cells (Y-79 NEI, WERI Rb-1) as well as two subcultured Y-79 lines (ATCC and GM01232C). High expression of alpha B-crystallin may be involved in tumor growth and/or be a marker for general oncogenic "stress" in the tumor tissue. PMID- 8482113 TI - An instrument for quantifying meibomian lipid on the lid margin: the Meibometer. AB - An instrument, the Meibometer, is described for estimating the casual level of meibomian lipid on the human eyelid margins, adapted from a commercially available instrument used for measurement of skin surface lipid. A loop of plastic tape is pressed onto the everted lower lid margin to lift off a blot of lipid. The resultant change in light transmission of the tape is read by a photometer. Readings are not affected by side (R or L), time of day or lid surface temperature. After cleaning lipid from the lid margins with hexane, the rate of recovery per 10 blinks, as a percentage of the pre-cleaned level, was measured as 33.7 +/- 5.8 (mean +/- SE). This rate of delivery appears to provide enough lipid for complete resurfacing of the preocular tear film with every blink. Over short periods no detectable lipid was delivered in the absence of blinking. PMID- 8482114 TI - The casual level of meibomian lipids in humans. AB - Using a modified skin surface lipid measuring instrument, the Meibometer, the amounts of meibomian lipid on the lid margins (the casual levels) of 421 subjects aged 1 to 94 years were measured. The lowest levels were found in children younger than 14 years (means +/- S.E.: males = 1.48 +/- 0.17, females = 1.53 +/- 0.17 micrograms lipid/mm2 lid margin surface) and rose with age, the highest levels being found in males aged 60-69 years (mean +/- S.E. = 3.26 +/- 0.18 micrograms lipid/mm2 lid margin surface). Male levels were higher than females in the 20-29 years age group but male and female levels became indistinguishable above the age of 50. These age- and sex-related changes differed markedly from those seen in skin surface lipid levels. The age-related changes in the casual levels of lid lipids remain unexplained although an endocrinological mechanism modified by morphological factors is considered. PMID- 8482115 TI - A Na+/Ca2+ exchange mechanism in apical membrane vesicles of the retinal pigment epithelium. AB - The retinal pigment epithelium (RPE) lying between the neural retina and the choroid, performs as a transport organ for solutes and water between the choriocapillaries and the subretinal space. It also has the function to maintain the microenvironment of photoreceptors including the regulation of calcium ions during light or dark adaptation. In order to further elucidate the transport functions of the RPE, apical membranes were isolated from RPE by differential precipitation with divalent ions. In this work bovine tissues were used as well as elasmobranch tissues. For the latter, we have already purified and characterized membrane vesicles in a previous paper. Na(+)-K(+)-ATPase, alkaline phosphatase, and 5'-nucleotidase, which are marker enzymes of the apical membrane, were highly enriched in the final membrane fraction. The majority of the fraction consists of right side out vesicles. The fluorescent indicator for sodium, SBFI, or the calcium specific indicator, Fura-2, were pre-loaded into the apical membrane vesicles of RPE of either dogfish eyes or bovine eyes. When an outwardly-directed Ca2+ gradient was formed across the vesicular membranes, the Ca2+ influx was also enhanced by 136% for dogfish RPE and 167% for bovine RPE. This Na+ gradient dependent Ca2+ influx was blocked by bepridil, an antiarrhythmic agent which is a Na+/Ca2+ exchanger inhibitor. These results indicate that a Na+/Ca2+ exchanger is present in the apical membrane of bovine and dogfish RPE. PMID- 8482116 TI - Identification and characterization of arylamine N-acetyltransferase activity from the bovine retinal pigment epithelium. AB - Arylamine N-acetyltransferase (NAT) activity was identified and characterized in bovine retinal pigment epithelium (RPE) cells. Upon examining the RPE supernatant for multiple ionic species, one major NAT activity peak was detected. Based upon its substrate specificity, it is best described as an arylamine NAT. However, there was detectable arylalkylamine NAT activity within this peak. Further purification via size-exclusion HPLC revealed multiple peaks of NAT activity, although the major peak (around 30 kDa) again predominantly exhibits arylamine NAT activity. However, substrate specificity studies indicate that this arylamine NAT activity is able to acetylate specific arylalkylamine substrates. This arylamine NAT demonstrates a monomorphic pattern of acetylation since it acetylates rho-aminobenzoic acid rather than sulfamethazine. It also demonstrates a low sensitivity to methotrexate inhibition indicated by the high IC50 value (570 microM). The mode of inhibition by methotrexate is uncompetitive as demonstrated by kinetic analysis. PMID- 8482117 TI - Raman structural characterization of clear human lens lipid membranes. AB - Raman spectroscopy was used for the first time to characterize the structure of lipid membranes prepared from the nuclear and cortical regions of 48 and 69 year old clear human lenses. The interface region carbonyl band appears as a doublet at 1742 and 1728 cm-1. The lower frequency band is characteristic of a hydrogen bonded carbonyl group, perhaps to bilayer water. From the intensity of the curve fit bands, we calculate that 43% of the carbonyl groups are hydrogen bonded. Our data show that the hydrocarbon chains of the nuclear lipids are 1.4 times more saturated than those of the cortical lipids. The molar ratio of phospholipid CH2/= C-H groups was calculated to be 13 and 18 for cortical and nuclear lipids, respectively. Hydrocarbon chain disorder was estimated to be 72 and 58% (+/- 8% disorder) for the cortical and the nuclear lipids, respectively. Raman spectroscopy is sensitive to structural differences in various regions of the lipid bilayer and could be an effective tool to explore lipid and protein interactions in terms of lens region, age and opacity. PMID- 8482118 TI - Advances in maxillofacial imaging. AB - The maxillofacial region, extending from the base of the skull to the hyoid bone, is one of the most anatomically complex regions of the body. This area contains elements and organs belonging to a number of different systems that can be affected by a variety of local and systemic pathologic processes. Diagnostic imaging has assumed a central role in the evaluation of this region. In the following monograph, we present the reader with an overview of contemporary maxillofacial imaging, focusing on three areas: recent technical advances that impact on the diagnosis of the maxillofacial region, the appearances of various maxillofacial lesions on different imaging modalities, and an overview of the role of diagnostic imaging in the evaluation of the orthognathic patient. In the first section, we focus on recent technical advances in diagnostic imaging as they relate to the maxillofacial region. Imaging modalities discussed include panoramic radiography and three-dimensional imaging. We also examine the uses of recently developed computed tomography software for the evaluation of the dental implant patient and discuss the roles of both noninteractive and interactive software in this process. The second section focuses on the radiographic appearance of a number of common lesions involving the maxillofacial region. In this section, we use the gamut approach to examine a number of developmental, inflammatory, neoplastic, metabolic, and traumatic lesions or disorders. In the last section, we briefly review the subject of orthognathic surgery and the role of diagnostic imaging in the preoperative and postoperative evaluation of the orthognathic patient. The radiographic appearance of some of the more commonly performed midfacial osteotomies are presented. PMID- 8482119 TI - [Hygienic prerequisites of ambulatory surgery]. PMID- 8482120 TI - [Diagnostic and therapeutic arthroscopy in acute trauma of the knee joint]. PMID- 8482121 TI - [Status of arthroscopy in diagnosis and therapy of injuries of the shoulder joint]. PMID- 8482122 TI - [Indications for diagnostic and therapeutic arthroscopy of "small joints" (elbow, upper ankle joint, wrist joint, hip joint]. PMID- 8482123 TI - [Effect of intraoperative radiotherapy on postoperative follow-up of pancreas cancer]. AB - Surgical therapy alone has not been able to improve significantly long-term survival in cases of pancreatic carcinoma. Improvement can only be expected by more successful local and systemic tumor control. To achieve the former intraoperative radiotherapy (IORT) with high-energy electrons has recently been introduced into clinical practice. Between June 1989 und June 1991 23 patients underwent IORT while receiving palliative (n = 16) and curative (n = 7) procedures. During the same period 36 patients were operated upon without IORT. Irradiated patients suffered far more complications. A positive effect on survival or pain control in palliatively operated cases could not be demonstrated. Prolonged survival after curative resections with IORT seems probable but can not be proven due to small number of patients. Further progress requires combination of IORT with postoperative radiochemotherapy. PMID- 8482124 TI - [Arterial vascular injuries in fractures or dislocations of the lower extremity. Therapeutic concept and results]. AB - Combinations of fractures or dislocations with vascular damage of the leg have a high incidence of amputation or severe functional deficit. With this type of lesion 22 patients were treated at "Bergmannsheil" from 1986 to 1991. Using a pre , intra- and postoperative protocol, the amputation rate decreased to 18%. More than 80% of the patients had a good function of their leg with only minor joint restrictions. PMID- 8482125 TI - [Intramedullary nailing of fractures during the growth period with a new implant]. AB - Intramedullary nailing with flexible titan pins is a simple and safe method for the treatment of fractures in children. Avoiding the epiphysis two pins are introduced into the medullary space in a double-crossing way to stabilise diaphysial fractures of bigger bones such as femur, tibia or humerus. Forearm fractures are splinted with a single pin each to radius and ulna. The method is also practicable in proximal fractures of the radius, reduction and stabilisation can be achieved with an intramedullary pin in one step avoiding arthrotomy. PMID- 8482126 TI - [Value of heterotopic finger replantation]. AB - Multidigital amputations represent a challenging problem with regard in restoring optimal sensomotoric hand function. Often orthotopic finger stumps or the separated digits are unfit for conventional replantation. This condition is an imperative indication for transpositional replantation. Among 24 heterotopic replantations the survival rate was 82 percent. The favorable finger transfer was a pollizisation, followed by a substitution of the middle finger and finally creating an expanding opposite grip on the ulnar site of the hand. Secondary corrective procedures have been performed in 37.5 percent. To evaluate the global hand function score systems according to Millesi or Tamai have been applied. 65 percent presented a "good" subjective and objective hand function as to Tamai. However the regain of hand function has to be aspired much more in the single and individual case of transpositional replantations when compared to the Millesi score system. PMID- 8482127 TI - [Plasma cell and sclerosing osteomyelitis. A follow-up of 21 patients]. AB - Plasma cellular osteomyelitis was seen in the metaphysis while sclerosing osteomyelitis affected the diaphysis of long bones. In only about 20% of both forms local bacteria were noted. The onset of symptoms was inconspicuous and both clinical and radiological signs were nonspecific. Curettment or resection usually cured the disease. In some cases, however, aggressive surgery was necessary. As to surgery and outcome sclerosing osteomyelitis appeared less riskful than plasma cellular osteomyelitis. Both forms apparently represent the same basic pathological condition. PMID- 8482128 TI - [Laparoscopic resection of liver metastasis]. AB - Six weeks after a partial colon resection because of an adenocarcinoma of the sigmoid we removed a solitary liver metastasis (6th segment) by laparoscopic technique in a 63-year-old patient. Operation time was 95 min, the postoperative course was uneventful and the patient was discharged at day 6 postoperatively. PMID- 8482129 TI - [Ackerman tumor (verrucous carcinoma) of the perineal region. Differential diagnosis of anus cancer]. PMID- 8482130 TI - [Transhaesio intestini tenuis supragastrica as a sequela of colon resection in childhood]. PMID- 8482131 TI - [Subcutaneous CO2 emphysema after laparoscopic cholecystectomy]. PMID- 8482132 TI - [HIV-infection]. PMID- 8482133 TI - [Blood transfusion]. PMID- 8482134 TI - [Errors and danger in laparoscopic appendectomy]. PMID- 8482135 TI - [Errors and danger in laparoscopic cholecystectomy]. PMID- 8482136 TI - [Errors and dangers of laparoscopic anti-reflux surgery]. PMID- 8482137 TI - [Errors and danger in hernia surgery]. PMID- 8482138 TI - [Technique and long-term results of thoracic and thoraco-abdominal aortic diseases]. PMID- 8482139 TI - [Asymptomatic carotid stenosis: is there an indication for operation?]. PMID- 8482140 TI - [Bypass or thrombendarterectomy?--Reconstructive procedures in arterial occlusive disease of the pelvic area]. PMID- 8482141 TI - [The Gastrointestinal Quality of Life Index. A clinical index for measuring patient status in gastroenterologic surgery]. AB - Since the measurement of quality of life is a relevant endpoint of patient assessment, an international team of methodologists and surgeons have developed a new system-specific index. In different phases, items were collected, tested, rejected or retained and finally verified by international experts. The instrument was also validated against other generic measures, it was compared to 150 normals, tested for reproducibility with 50 stable patients and for responsiveness with 159 patients undergoing laparoscopic cholecystectomy. The product is a bilingual (German and English) questionnaire containing 36 items. Although further testing is in order, we conclude that the Gastrointestinal Quality-of-Life Index is ready to be used in clinical practice and research. PMID- 8482142 TI - [DNA analysis in stomach cancer--correlation of aneuploidy with tumor site]. AB - The DNA status and the proliferative activity was determined in 37 gastric carcinomas applying computerized image analysis. Aneuploidy was found in 51.4% (n = 19) of the tumors. Comparing diploid and aneuploid lesions the latter ones had statistically significant increased DNA amount, DNA index and proliferative rate (7.4 pg, 1.03 and 16.4% versus 12.8 pg, 1.78 and 30.7%; p < 0.05). Aneuploidy occurred more frequently in tumors at proximal sites (p < 0.05), but was not associated with histological type, differentiation and tumor stage. The prognostic impact of DNA aneuploidy remains controversial, since tumor aggressiveness per se is not directly related to aneuploidy. PMID- 8482143 TI - [Lung resections for pulmonary infections in intensive care patients]. AB - Pneumonia occurs in about 60% of ventilated patients with a lethality of approximately 40%. Since 1980 we performed a thoracotomy in 16 patients of an intensive care unit suffering from a lung infection (mean age 34 years). In all patients an adequate antibiotic therapy was unsuccessful. By means of the computed tomography we could ascertain a lung infection limited to one part of the lung, mostly combined by an abscess. We performed 14 lobectomies and one atypical wedge resection and segment resection each. Postoperatively 8 patients died: Three of them because of a persisting septic shock and five because of their multiple injuries. Lung resection is a good treatment in case of a lung infection with septic complications. PMID- 8482144 TI - [Resection of liver metastases of colorectal cancers. Results and prognostic factors]. AB - Between 1985 and 1991 268 liver resections were performed at the Department of Surgery of the University of Hamburg. 89 patients underwent liver resections because of colo-rectal secondaries. 82 patients could be followed for more than 1 year postoperatively. Their courses were analysed regarding the prognostic factors: age, sex, localisation of the primary tumor, size, number and localisation of metastases and radicality (R0-R1-R2-stage of resection). The results showed, that a significant prognostic influence regarding the long-term survival rate could only be observed in patients, in which a R0-resection with a tumor-free margin of more than 1 cm was performed. In these patients the cumulative 5-year survival rate was 37% with a median survival time of 39 months. In patients with a tumor-free margin < 1 cm (R0b) the long-term prognosis did not differ significantly from cases with R1 or R2 resections (under 10%). PMID- 8482145 TI - [Endorectal ultrasound in diagnosis and therapy planning of broad-base rectal adenomas]. AB - In this study the value of endorectal ultrasound in diagnosis and therapy of large rectal adenomas is shown. Between January 1988 and August 1992 93 patients with the primary diagnosis of adenoma proven by biopsy were examined by endorectal ultrasound. Sonographical differentiation of adenoma and carcinoma was done by echo-structure. Enlarged lymph nodes can be detected too. In 34 of 91 patients carcinoma was found by endorectal ultrasound and 28 were verified histologically. Sensitivity of endorectal ultrasound in detection of carcinoma in enlarged adenomas is 96%. Only preoperative endorectal ultrasound could give decisive criteria to take a second biopsy, to avoid mucosectomy in case of a malignoma or give the advice for a radical operation according to the tumor stage. Further staging of adenomas and small carcinomas is excellent by endorectal ultrasound and the right indication of local therapy can be confirmed. PMID- 8482146 TI - [Current status of gallstone surgery in Germany. Results of a survey and retrospective analysis of 27,403 interventions--open vs. laparoscopic surgery]. AB - Based on a representative poll, which included a retrospective data analysis, the current surgical approach to gallstone disease in Germany is presented. A total of 25,955 procedures in 1991 is analysed. 24.9% of all cholecystectomies were done laparoscopically. In 1992, already 81.4% of all surgeons reported own experiences with this new technique. Comparing open procedures with laparoscopic cholecystectomy the latter showed a lower incidence of complications (6.8 vs 8.7%) and perioperative death (0.14 vs. 0.43%). In contrast, relaparotomies were more frequent in the laparoscopy group (1.48 vs. 0.84%). The diagnostic and therapeutic approach for common bile duct stones is currently changing. There is a tendency towards less invasive endoscopic and laparoscopic procedures and towards their combination, respectively. PMID- 8482147 TI - [Laparoscopic cholecystectomy in Austria. The Austrian 1991 register]. AB - The number of surgical units, performing laparoscopic cholecystectomies (LC) in Austria increased from 24 hospitals (20%) in 1990 to 85 hospitals (70%) in 1991, performing 7351 LCs. In 97% the outcome was uneventful, the conversion rate was 2.1%; 0.85% required secondary laparotomy. Common bile duct lesion occurred in 0.5%, lethality was 0.1% (n = 4). Because of the cooperation of all surgeons Austria is the only country to present actual numbers concerning acceptance and penetration rate of LC. PMID- 8482148 TI - [Laparoscopic cholecystectomy in Switzerland. Critical retrospective evaluation of the first 3,722 cases. Swiss Professional Society of Laparoscopic and Thoracoscopic Surgery]. AB - In a national prospective multicenter study 3722 laparoscopic cholecystectomies (LC) performed by 179 surgeons in 50 Swiss institutions were analysed with special regard to technique and complications. Conversion to open cholecystectomy was necessary in 259 patients (7.0%), either expectively without intraoperative complications (4.5%) or due to intraoperative complications (2.5%). Three patients (0.08%) died within 30 days after operation and a total of 39 patients (1.0%) had to be reoperated. 31 (0.8%) bile duct injuries were registered. Common bile duct (CBD) stones were treated mainly by ERCP. In 8 cases laparoscopic removal of common bile duct stones was attempted and performed successfully in 6 patients. Postoperatively patients were discharged home after a mean of 4.4 days and returned to work after 14.0 days (range: 2-28). Laparoscopic cholecystectomy became the gold standard to remove the gallbladder, but further development is needed, to establish laparoscopic treatment of biliary tract stones in the near future. PMID- 8482149 TI - [Laparoscopic splenectomy]. AB - From August until October 1992 laparoscopic splenectomy has been performed upon three patients with idiopathic thrombocytopenia. The splenic vessels were divided by an Endo-GIA. The spleen could be removed through a slightly extended trocar incision. The Idiopathic thrombocytopenia without an enlarged spleen provides a possible indication for laparoscopic surgery. PMID- 8482150 TI - [Experiences with laparoscopic technique in anti-reflux surgery]. AB - The introduction of the laparoscopic techniques in antireflux surgery has created hopes for an improvement in the patients' outcome. Initial experience with minimally invasive procedures show that the application in antireflux surgery is possible without major problems. However, the functional result of antireflux surgery rather depends more on a differentiated indication for operation and an operative procedure designed to remove or compensate the underlying pathophysiologic functional defect. The method of access is of lesser priority. The promising results of this series may encourage to continue the demonstrated protocol and operative technique. However, generalized application of laparoscopic antireflux surgery should not be performed until further data of its advantages are available. PMID- 8482151 TI - [Thoracoscopic lobectomy in the animal model]. AB - To evaluate the possibility of a pure thoracoscopic lobectomy by preparation and selective division of hilar structures we performed left cranial lobectomies in 5 Gottingen mini-pigs. The vessels and the main bronchus were isolated and divided by an Endo-GIA stapler. As an alternative technique we used clips or endoscopic ligation. Inside the thoracic cavity the resected lobes were divided into 2 or 3 parts by the Endo-GIA. They could be extracted without destroying the tissue therefore making macroscopic examination possible. The intraoperative blood loss was minimal and all the pigs survived the operation. Two pigs were sacrificed initially, the remaining three one month later. These three showed no evidence of pleural fistula or atelectasis in remaining lung tissue either macroscopically or histologically. It appears that thoracoscopic selective lobectomy is technically possible at least in pig studies. Further studies will show whether thoracoscopic lobectomy in patient with malignancy is as effective as open radical thoracotomy techniques and if endoscopic mediastinal division is possible. PMID- 8482152 TI - [Reinforcement of the peritoneal sack using a large prosthesis (Stoppa operation)]. AB - To avoid repeated dissection and repair of used-up defect margins a truly innovative concept of eliminating recurrent hernias has been introduced by Stoppa. A giant prosthesis of polyester is inserted through a sub-umbilical midline incision and envelopes the inferior visceral sac, which is dissected bilaterally. The prosthesis is held in place against the bony pelvis and abdominal musculature by the pressure of the abdominal viscera and without sutures; it has no slit for the spermatic cord and prevents passage of viscera through a hernial orifice, even left open. PMID- 8482153 TI - [Treatment of recurrent inguinal hernia by implantation of a pre-peritoneal prosthesis. Results of a prospective study]. AB - 44 patients with 47 recurrent inguinal hernias entered a prospective study. All patients were operatively managed by a standardized technique using a polypropylene (Prolene) mesh inserted through a pre-peritoneal approach. Operating in the pre-peritoneal space avoids dissection of the scared cord and the "inlay" prosthetic mesh safely creates a new "fascia transversalis" with a low rate of recurrences. All patients were personally controlled every 6 months with a follow-up time of 12 to 60 months (mean 20.2 months). The low postoperative morbidity included only one seroma, no infection and no testicular complications. We observed one recurrence occurring 6 months after surgery (2%). The described operative technique using an inlay patch is recommended as the therapy of choice in all recurrent groin hernias. PMID- 8482154 TI - [Laparoscopic repair of inguinal hernia by subperitoneal prosthesis implantation (Stoppa operation)]. AB - The authors present their technique of inguinal hernia treatment by the putting of a very tall (15 x 10 cm) polypropylene prosthesis in its place in subperitoneal by laparoscopic access. From May 1, 1991 until January 31, 1992, 110 inguinal hernias (64 right and 46 left hernias) were operated on 93 patients. The first results are analysed: there was in particular no recurrence with an average of 4.3 months set-back. It should be observed that about 40% of the patients were operated under epidural analgesia. PMID- 8482155 TI - [Laparoscopic herniorrhaphy of inguinal hernia. Reinforcement of the transverse fascia with surgical mesh]. AB - A basic principle of inguinal herniorrhaphy is the reconstruction of the transverse fascia. This laparoscopic technique described, consists in an augmentation of the transverse fascia by nonabsorbable mesh in pre-peritoneal position. Some aspects should be recommended for laparoscopic herniorrhaphy: The anatomic structures must be dissected exactly. The prosthetic mesh should be fixed to the fascia by multiple staples. With indirect inguinal hernias the mesh should encircle the spermatic cord. PMID- 8482156 TI - [Carcinoma of the small intestine in Crohn disease. Case report and review of the literature]. PMID- 8482157 TI - [Pneumatosis coli--a rare cause of invagination ileus in the adult]. PMID- 8482158 TI - [100 years Murphy button: development, dissemination and further development]. PMID- 8482159 TI - [Thoracoscopic lobectomies]. PMID- 8482160 TI - Thoracotomy for colon and rectal cancer metastases. AB - Between 1978 and 1990, 23 patients underwent 35 thoracotomies for metastatic colorectal cancer. The pulmonary disease was diagnosed within an interval of 0 to 105 (average, 33.4) months after colon resection. Fifteen patients underwent a single thoracotomy; 12 patients had solitary lesions, and three patients had multiple nodules. Eight patients underwent multiple thoracotomies. The median survival following thoracotomy was 28 months; three-year survival was 45 percent, and five-year survival was 16 percent. Factors that had no significant bearing on survival included origin and stage of the primary tumor and patient age and sex. An interval before thoracotomy of three years had an impact on survival approaching statistical significance (P = 0.17). Patients who underwent multiple thoracotomies had a significantly prolonged survival (P = 0.04). Patients who underwent a single thoracotomy for a solitary lesion had a significantly prolonged survival compared with patients who had a single thoracotomy for multiple metastases. After thoracotomy, 14 patients eventually developed recurrent disease, which was confined to the lung in only four patients. Of these 14 patients, 11 subsequently died of cancer. We conclude that thoracotomy for metastatic disease should be considered when the primary tumor is controlled, the lungs are the only site of metastatic disease, and there is adequate lung reserve to withstand surgery. Survival following thoracotomy may be influenced by the interval before diagnosis, the number of pulmonary nodules, and the number of thoracotomies performed. PMID- 8482161 TI - How accurate is clinical examination in diagnosing and quantifying pelvirectal disorders? A prospective study in a group of 50 patients complaining of defecatory difficulties. AB - We prospectively evaluated 50 patients (38 females and 12 males; mean age, 44.7 +/- 15 years) who complained of defecatory difficulties to determine the accuracy of the clinical examination in diagnosing and quantifying pelvirectal abnormalities. Each parameter was then compared with the features of anorectal manometry and evacuation proctography performed by two independent observers. Global agreement between clinical diagnosis and the reference method (radiology for rectoceles, rectal intussusceptions, and abnormal perineal descent; manometry for anismus) was observed in 80 percent of cases. In rectoceles, anismus, and rectal intussusceptions especially, excellent negative predictive values were obtained (96, 96, and 80 percent, respectively). Clinical examination always diagnosed high-grade intussusceptions. Nevertheless, abnormal perineal descent was poorly evaluated in 20 patients. When compared with anal manometry, digital assessment was able to quantify resting and squeeze pressures and length of the anal canal with excellent correlation and good global agreement as well as predicting a short or hypotonic anal canal. Clinical assessment is usually sufficient and accurate in most pelvirectal disorders encountered in patients complaining of defecatory difficulties. Both anorectal manometry and evacuation proctography retain a definite but limited place in investigating pelvirectal disorders. PMID- 8482162 TI - Subcutaneous morphine pump for postoperative hemorrhoidectomy pain management. AB - PURPOSE: Many anorectal procedures are currently being performed on an outpatient basis, hemorrhoidectomy being the exception because of the need for parenteral narcotics postoperatively. We investigated the effectiveness of a subcutaneous morphine pump (SQMP) for outpatient posthemorrhoidectomy pain control. METHODS: In Phase 1 of our study, 22 patients undergoing radical hemorrhoidectomy were started on an SQMP protocol postoperatively. Twenty-nine patients received conventional postoperative narcotic dosing. In Phase 2, 19 patients enrolled in an SQMP protocol underwent hemorrhoidectomy in an ambulatory setting. Length of hospitalization, catheterization rate, and pain control were evaluated. RESULTS: In Phase 1, zero patients in the study group and two in the control group required additional hospitalization beyond 23 hours for pain control. The rates of catheterization were similar between the two groups. Pain control was considered satisfactory in 21 of 22 study patients. There was no correlation between pain level and morphine dose. Eighteen of 22 patients experienced minor side effects, necessitating pump removal in two patients. In Phase 2, 18 of 19 patients on the SQMP were discharged from the recovery room. Cost analysis shows the combination of outpatient hemorrhoidectomy and the SQMP to be cost-effective in comparison with an inpatient stay. CONCLUSIONS: The SQMP enables hemorrhoidectomy to be done on an outpatient basis. It provides effective pain control, enjoys high patient acceptance, and is cost-effective. PMID- 8482163 TI - Autologous fibrin glue in the treatment of rectovaginal and complex fistulas. AB - This nonrandomized series reports the use of autologous fibrin glue to treat complex rectovaginal and anorectal fistulas. The use of an autologous source to prepare fibrin glue eliminates the risk of disease transmission. Ten patients, six women and four men, with complex fistulas were treated with autologous fibrin glue application. Five patients had rectovaginal fistulas; one of them had Crohn's disease. Five patients had complex anal fistulas; two of them had Crohn's disease, and one had a large postanal ulcer associated with HIV disease. All patients had outpatient preoperative mechanical bowel preparation and prophylactic parenteral antibiotics. Six of the ten patients (60 percent) reported complete healing of the fistulas. Follow-up ranged from three months to one year. Four of five rectovaginal fistulas healed. The two patients with Crohn's disease and complex anal fistulas and the patient with HIV disease did not heal, but all three reported significantly less drainage. Autologous fibrin glue is a viable alternative for the treatment of recurrent rectovaginal and complex abscess/fistulas. PMID- 8482164 TI - Morphometric analysis of colorectal cancer. AB - Thirteen nuclear and cellular morphometric variables were measured in 312 cases of colorectal adenocarcinoma. All variables, except nuclear shape factors, differed significantly (P < 0.001) between normal colorectal and tumor tissue. In adenocarcinomas, epithelial nuclei in well-differentiated mucosa tended to be elliptic, while those in poorly differentiated mucosa were more spheric. Increasing values of maximum nuclear and elliptic diameter were associated with progression from none to simple tubule configuration (P < 0.001), none to easily discerned nuclear polarity (P < 0.001), and expanding growth pattern (P < 0.001). Univariate survival analysis revealed that none of the morphometric variables was significantly related to patient survival. Multivariate regression analysis showed that no morphometric variable could add significantly to a model containing the variables of patient age, Dukes stage, and tumor differentiation. Morphometry may be useful in distinguishing malignant from normal tissue and degrees of differentiation, but it is of little prognostic value in colorectal adenocarcinoma. PMID- 8482165 TI - Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model. AB - Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n = 33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P < 0.05). Gross inspection showed severe colonic inflammation through the first week (mean score = 4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonic inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans. PMID- 8482166 TI - Initial experience with laparoscopic appendectomy. AB - As experience with laparoscopy increases, new applications in general surgery are being identified. Treatment of acute appendicitis through the laparoscope has been proposed. We present our initial experience with this new technique. Over a 12-month period, laparoscopic appendectomy was attempted in 29 patients. There were no intraoperative complications. Two cases required conversion to the open technique owing to gangrene at the appendiceal base. The average operating time was 64 minutes. Two of nine patients with perforated appendicitis developed a pelvic abscess, and one patient developed wound cellulitis. Pain medication requirements were minimal, bowel function returned rapidly, and half of the patients were discharged on postoperative day one or two and returned to normal activity within one week. Based on our initial experience, it appears that laparoscopic appendectomy is a safe and effective technique for managing acute appendicitis and offers advantages in terms of decreased pain, decreased hospital stay, and a rapid return to normal activities. PMID- 8482167 TI - Cellular proliferation at sutured and sutureless colonic anastomoses. AB - Elevated cellular proliferation in the vicinity of an anastomosis may explain the enhanced susceptibility to carcinogens. The aim of this study was to determine whether anastomotic cellular proliferation was altered by different suture materials and whether a rise in cell turnover also occurred after a "sutureless" closure. A transverse descending colon enterotomy was repaired with interrupted sutures of 5/0 silk (n = 20), stainless steel (n = 20), or Vicryl (Ethicon, Inc., Somerville, NJ) (n = 20) or by a sutureless technique (n = 20). Using a stathmokinetic technique, crypt cell production rates (CCPR) were calculated at the anastomosis and in the adjacent colon at varying intervals between one week and six months after treatment. Overall colonic cellular proliferation appeared to be elevated at a sutured colotomy for at least three months (P < 0.05). In contrast, no significant elevation in cellular proliferation was observed at sutureless anastomoses. The duration of elevated proliferative response varied among the sutures. PMID- 8482168 TI - Parameters of anorectal and colonic motility in health and in severe constipation. AB - Anorectal function and colonic transit was assessed in 17 severely constipated patients and 15 age-matched controls. The constipated patients were divided into those who had "immobile perineum" (perineal descent < or = 1.0 cm during attempted defecation) and those who had a normal descent (> 1.0 cm) of the perineum. When constipation was accompanied by an immobile perineum, patients had impaired balloon expulsion, impaired and delayed artificial stool expulsion, decreased straightening of the anorectal angle, decreased descent of the pelvic floor with defecation, and prolonged rectosigmoid colon transit compared with the patients with constipation who had a mobile perineum and with normal controls. The mobile-perineum group differed from controls only in colon transit times, having prolonged total colon transit. Anal sphincter resting pressures, immediate artificial stool expulsion, resting anorectal angles, and electromyography of the external anal sphincter and puborectalis did not differentiate the constipated patients from the controls. We concluded that descent of the perineum of < 1 cm was associated with impaired expulsion, an adynamic anorectal angle, and slowed distal colon transit. This simple sign of pelvic floor function distinguished constipated patients with disordered expulsion from constipated patients with normal pelvic floor function. These patients may respond poorly to surgery and conventional management and would therefore be candidates instead for pelvic floor retraining. Accurate characterization and appreciation of pelvic floor dysfunction in patients with severe chronic constipation may improve the selection for and results of surgical and nonsurgical intervention. PMID- 8482169 TI - Redo pouches: salvaging of failed ileal pouch-anal anastomoses. AB - From October 1, 1984 to December 31, 1991 at the Clinica Chirurgica II of the University of Bologna, 140 patients submitted to ileal pouch-anal anastomosis for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Nineteen patients (13.5 percent) developed septic complications. Of these, 11 patients (7.8 percent) had pelvic sepsis. Eight patients required further surgical intervention. Five patients underwent the redo pouch procedure. Another redo pouch was performed in a patient who had previously, in another hospital, had an ileal pouch-anal anastomosis placed and then removed because of ischemic necrosis of the reservoir. No deaths are reported in the reoperated patients. Currently, five of the six patients who underwent the redo pouch procedure have a well functioning ileoanal anastomosis. The redo pouch procedure should always be attempted prior to the establishment of pelvic fibrosis. PMID- 8482170 TI - Level of serum gastrin as a predictor of liver metastasis from colorectal cancer. AB - There have been no reports on the relationship between serum gastrin level and liver metastasis in human colorectal cancer. One hundred forty patients who underwent surgery for colorectal cancer (T2 or more) were enrolled in this study. Fasting serum gastrin level was determined prior to the surgery. Incidence of liver metastasis was significantly (P < 0.01) higher in patients with a serum gastrin level of > or = 150 pg/ml (37 percent; 14/38) than in those with a serum gastrin level of < 150 pg/ml (12 percent; 12/102). As for the tumors with venous invasion, liver metastasis was detected in 11 of 55 patients (20 percent) with a serum gastrin level of < 150 pg/ml; however, it was detected in 11 of 19 patients (58 percent) with a serum gastrin level of > or = 150 pg/ml (P < 0.01). These results suggest that serum gastrin serves as a useful predictor of liver metastasis from colorectal cancer and that the predictability of liver metastasis can be improved when both serum gastrin level and venous invasion are considered. PMID- 8482171 TI - Ripstein procedure is an effective treatment for rectal prolapse without constipation. AB - The operation of choice for complete rectal prolapse is controversial. We reviewed 169 patients undergoing 185 surgical procedures for rectal prolapse over a 27-year period. The most common surgical procedure employed was the Ripstein procedure (n = 142) and is the focus of this report. Other surgical procedures used included resection rectopexy (n = 18), anterior resection (n = 7), Altemeier's (n = 9), Delorme's (n = 2), and anal encirclement (n = 7). The median age was 59 years (range, 12-94 years), and the female-to-male ratio was 5:1. The incidence of fecal incontinence, solitary rectal ulcer syndrome, and prior surgery elsewhere for rectal prolapse was 40 percent, 12 percent, and 19 percent, respectively. Operative mortality was 0.6 percent; morbidity was 16 percent. Median follow-up was 4.2 years (range, 1-15 years). Complete recurrence of prolapse after the Ripstein procedure was 8 percent; one-third of these patients recurred 3 to 14 years after surgery. Fecal incontinence improved after the Ripstein procedure or resection rectopexy in about half the patients. Persistence of prior constipation was more common after the Ripstein procedure than after resection rectopexy (57 percent vs. 17 percent; P = 0.03, chi-squared). Fifteen patients developed constipation for the first time after the Ripstein procedure. About one in three patients, irrespective of surgical procedures, remained dissatisfied with the final outcome despite anatomic correction of the prolapse. The Ripstein procedure has proven to be a safe procedure with good anatomic repair of the prolapse and may improve continence. In the presence of constipation, procedures other than the Ripstein procedure may be preferable. PMID- 8482172 TI - Self-expanding stainless steel stent application in rectosigmoid stricture. AB - In recent years, several reports on the experimental and clinical applications of the Gianturco stent (self-expanding stainless steel stent) have been published. However, to our knowledge, the use of stents in rectosigmoid strictures has not been reported. We used self-expanding stainless steel stents to dilate rectosigmoid strictures caused by nonresectable recurrent neoplasm. Insertion and dilation (sigmoid colon and rectum) in two patients were successful. Accordingly, these patients were able to maintain bowel activity and avoid palliative loop colostomy. We believe that this procedure is effective for nonresectable rectosigmoid stricture due to recurrent neoplasm. PMID- 8482173 TI - The management of an ileostomy including its complications. 1952. PMID- 8482174 TI - L-carnitine for treatment of nonspecific proctosigmoiditis. PMID- 8482175 TI - Study of human gastroduodenojejunal motility. Applied physiology in clinical practice. PMID- 8482176 TI - Ambulatory esophageal manometry, pH-metry, and Holter ECG monitoring in patients with atypical chest pain. AB - Standard Holter electrocardiographic (ECG) monitoring was combined with ambulatory esophageal manometry and pH-metry in 25 patients with atypical chest pain in order to determine whether an association could be found between spontaneous pain episodes and ischemic ECG changes or esophageal dysfunction. Results of ambulatory testing were compared to those obtained with standard esophageal manometry and provocative testing. Twenty-two of the 25 patients experienced a total of 88 pain episodes during ambulatory testing. Although 15 of the 22 patients (68%) experiencing pain during testing had at least one pain episode that correlated temporally with gastroesophageal reflux, esophageal dysmotility or ischemic ECG changes, 65% of all pain episodes were unrelated to abnormal esophageal events or ECG changes. Seventeen percent of pain episodes were associated with gastroesophageal reflux, 15% with esophageal dysmotility, and 2% with a combined acid reflux and esophageal dysmotility event. Only one pain episode was associated with ischemic ECG changes. Twelve of the 15 patients with chest pain episodes associated with reflux or esophageal dysmotility had other identical pain episodes in which there was no correlation. Reproduction of a patient's pain during standard manometry with provocative testing did not predict a strong correlation between the patient's spontaneous pain episodes and esophageal dysfunction during ambulatory recordings. In summary, patients with atypical chest pain have relatively few spontaneous pain episodes that correlate with gastroesophageal reflux, esophageal dysmotility, or ischemic ECG changes. It appears that different stimuli can trigger identical episodes of chest pain, which suggests that many of these patients may have dysfunction of their visceral pain sensory mechanisms. PMID- 8482177 TI - Reliability and interobserver variability of ultrasonographic measurement of gastric emptying rate. AB - Scintigraphy and real-time ultrasound are valid techniques to measure parameters of gastric emptying. However, scintigraphy involves exposure to ionizing radiation, while the precision of real-time ultrasound has not been previously evaluated. The objectives of the present study were to determine the inter observer and day-to-day variability of liquid gastric emptying rate measured by real-time ultrasonography in healthy volunteers and to compare the gastric emptying rate of males and females. Twenty healthy volunteers had ultrasonographic measurement of gastric emptying rate after ingestion of 300 ml beef broth. Nine subjects had a concurrent assessment by a second observer. Nine subjects had two studies performed on different days by the same sonographer. The T1/2 for 20 subjects was 24.77 +/- 6.84 min with no difference between the half emptying time for males (25.89 +/- 6.99 min) and females (24.02 +/- 6.94 min). The Pearson and intraclass correlation coefficients for observations made by two observers were 0.83 and 0.625, with a difference due to observer of 2.37 min +/- 5.26 (NS). The test-retest reliability across successive days was 0.136, representing considerable day-to-day variability within subjects. The variability between subjects was also large, explaining up to 79% of the total variance. We conclude that ultrasound is a useful method to evaluate gastric emptying with good interobserver agreement. Due to substantial day-to-day variability, sample sizes larger than previously suggested are required to demonstrate clinically important changes in gastric emptying rate in clinical trials. PMID- 8482178 TI - Objective and subjective results of a randomized, double-blind, placebo controlled trial using cisapride to treat gastroparesis. AB - Cisapride, a relatively new gastrointestinal prokinetic agent, has been reported to increase gastric emptying and improve symptoms of gastroparesis. We investigated these effects of cisapride in patients with severe idiopathic and diabetic gastroparesis during an eight-week trial. The study design was a two week single-blind placebo run in period to exclude placebo responders, followed by a six-week randomized, double-blind, placebo-controlled treatment phase. Delayed gastric emptying of solids on radionuclide scan and a minimum symptom intensity score were inclusion criteria. Forty-three patients were entered: four placebo responders and one other patient were excluded, leaving 19 patients randomized to cisapride (20 mg per os three times a day before meals), and 19 patients to placebo. Seven individual symptoms of gastroparesis were scored in a daily diary and reviewed at two-week visits. Sixteen patients in the cisapride group were able to complete the trial compared to 12 on placebo. The gastric emptying study was repeated at the end of treatment or at the time of withdrawal for those who dropped out. Cisapride significantly increased solid gastric emptying relative to baseline (P = 0.005) whereas placebo did not (P > 0.10). Cisapride did not significantly improve any symptom of gastroparesis relative to baseline or to placebo. We conclude that in a population of severe, refractory gastroparetic patients cisapride significantly accelerates gastric emptying of a solid meal without significantly reducing symptoms during a short-term treatment trial compared to placebo. Further trials of cisapride in less advanced and "end stage" gastroparetics than studied here or combining cisapride with other prokinetic agents or antiemetics, are warranted. PMID- 8482179 TI - Effect of trimebutine maleate on emptying of stomach and gallbladder and release of gut peptide following a solid meal in man. AB - We investigated the effect of orally administered trimebutine maleate on gastric and gallbladder emptying and on the release of gut peptide, pancreatic polypeptide (PP), and gastrin in humans for 120 min after ingestion of a solid meal. Gastric emptying was measured by a radionuclide technique. Gallbladder emptying was estimated by real-time ultrasonography. The oral administration of 200 mg of trimebutine maleate significantly shortened the lag time in starting gastric emptying (P < 0.05). Considering gallbladder emptying, trimebutine significantly inhibited the fasting emptying induced by neural reflex. Postprandially, there was a tendency toward an accelerated gallbladder emptying in the early phase. Neither the maximal percentage of gallbladder emptying nor the time of peak gallbladder emptying were affected. Trimebutine significantly blunted the post-prandial PP response in the cephalic and gastric phases, reflecting a vagal-cholinergic activity (P < 0.05). The PP response in the intestinal phase was also blunted. Gastrin release was significantly augmented only during the period of fasting after drug administration (P < 0.05). The major effect of trimebutine maleate appears to be a shortening of the lag time at the start of gastric emptying probably via its anticholinergic activity. PMID- 8482180 TI - Gastric acid inhibits antral phase III activity in duodenal ulcer patients. AB - Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC. PMID- 8482181 TI - Voluntary suppression of defecation delays gastric emptying. AB - We wished to test the hypothesis that colonic loading with fecal material leads to delayed gastric emptying. Twelve healthy male volunteers were studied. Each of these subjects went through two randomized study periods of four days. In one of these, the subjects defecated upon urge, in the other period defecation was voluntarily suppressed. Gastric emptying of a semisolid meal (mashed potatoes) was measured with the noninvasive applied potential tomography technique. On day 3 no significant changes in gastric emptying were found, but on day 4 the emptying rate had decreased from 85.8 +/- 11.0%/hr (mean +/- SEM) to 70.3 +/- 10.9%/hr (P < 0.05) and the T50 had increased from 38.5 +/- 3.4 min to 46.2 +/- 4.0 min (P < 0.025). The duration of the lag phase (4.1 +/- 1.5 min) was not significantly altered by suppression of defecation. Our conclusion is that voluntary suppression of defecation delays gastric emptying in normal subjects. This "cologastric brake" may be involved in the pathogenesis of upper abdominal symptoms in constipated patients. PMID- 8482182 TI - Disturbed gastric and small bowel transit in severe idiopathic constipation. AB - Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (111In-containing pancake) and liquids (99mTc-containing orange juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal--up to 48% solid residue (median: 11% for patients and 0% for controls, P < 0.01) and 40% of liquid (median 9% vs 0%, P < 0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal < 4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482183 TI - Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat. AB - Neuropeptide Y is distributed abundantly not only in the brain, but also in the gastrointestinal tract and suppresses intestinal muscle contraction in isolated muscle preparations. The purpose of the present study was to determine whether centrally administered neuropeptide Y modulated gastric emptying and intestinal transit in conscious rats. Graded doses of neuropeptide Y were administered intracisternally 1 min before ingestion of test meals through an oral tube. Four hours after ingestion of 60 Amberlite pellets, the rats were sacrificed and residual pellets in the stomach and the small intestine segments were counted to calculate the solid meal transit rate. The liquid meal transit rate was calculated 1 hr after 0.07% phenol red ingestion by determining the residual phenol red in the stomach and the small intestine segments. Neuropeptide Y elicited potent suppression of gastric emptying and intestinal transit of both solid and liquid meals. Pretreatment with propranolol antagonized, whereas phentolamine did not affect, the suppressive effect of central neuropeptide Y. Although carbachol blocked the effects of neuropeptide Y, neither atropine nor hexamethonium altered the actions of neuropeptide Y. In conclusion, centrally administered neuropeptide Y strongly inhibited gastrointestinal transit by stimulating a beta-adrenergic pathway. PMID- 8482184 TI - Effect of misoprostol on postprandial intestinal motility and orocecal transit time in humans. AB - We measured the effect of misoprostol (M), a PGE1 analog, on duodenojejunal postprandial motor activity and orocecal transit in eight healthy volunteers. Intestinal motility was studied by an intraluminal catheter with three strain gauge transducers connected to a solid-state datalogger, and transit time was measured by a hydrogen breath test. Subjects were studied for two consecutive days and fed twice a day with a similar, 600-kcal meal. Misoprostol (M) at 800, 400, or 200 micrograms or placebo were taken orally before every one of the four meals. Transit time was measured after the morning meal on both days, after ingestion of either 800 micrograms of M or placebo. On four occasions, following M, the normal fed pattern was not established and the migrating motor complex (MMC) was not interrupted by the meal. In all other occasions, when the higher doses of M were given, the first 1-2 hr after the meal revealed a hypoactive bowel. This effect was inconsistently seen following 200 micrograms of M. Orocecal transit time was consistently and significantly shorter after M than placebo: 48.3 +/- 9.5 min vs 104.4 +/- 4.8 min, P < 0.0001. Four subjects had diarrhea during the study. We conclude that misoprostol, particularly at higher doses, has a profound effect on intestinal postprandial motility and results in accelerated transit time. The motility changes induced by M may be responsible, in part, for its effect on transit. PMID- 8482185 TI - Integration of canine proximal gastric, antral, pyloric, and proximal duodenal motility during fasting and after a liquid meal. AB - The aim was to investigate the integration of proximal gastric, antral, pyloric, and duodenal motility during fasting and after feeding. Using a proximal gastric barostat and a manometric assembly with an array of side holes astride the gastroduodenal junction, the gastrointestinal interdigestive migrating motor complex was detected in five of seven conscious fasting dogs. During phase III of the complex, which lasted a mean +/- SEM of 13 +/- 0.5 min, 9.6 +/- 0.9 volume waves were present in the proximal stomach. The volume waves were coordinated with clusters of antral waves 64 +/- 11% of the time and with inhibition of duodenal waves 91 +/- 3% of the time. A 300-ml calorie-dense liquid meal abolished the complex and promptly increased proximal gastric volume in five of six dogs. Volume waves were nearly completely suppressed, while antral waves decreased from 24 +/- 3.0 waves/10 min to 10 +/- 2.8 waves/10 min (P < 0.05) and isolated pyloric pressure waves increased from 7.2 +/- 2.8 waves/10 min to 22 +/- 3.3 waves/10 min (P < 0.005). In summary, proximal gastric motility was integrated with antral, pyloric, and duodenal motility under both fasting and fed conditions. The integrated patterns likely account for the efficient clearance of indigestible solids during fasting and the controlled emptying of nutrients with feeding. PMID- 8482186 TI - Effect of erythromycin on interdigestive gastrointestinal contractile activity and plasma motilin concentration in humans. AB - The effects of erythromycin (EM) on gastrointestinal contractile activity during the interdigestive period were investigated in seven healthy subjects using an infused catheter system, and the changes in the plasma motilin concentration were also determined. Graded EM doses (0.1-1.5 mg/kg) were administered intravenously over 5 min, usually during gastric phase I. EM induced interdigestive migrating contractions (IMCs). Their induction rate was low after low doses of EM, but gradually increased as the dose increased to reach 71.4% at an EM dose of 0.375 mg/kg. Strong contractions, which were quite similar to phase III activity of the stomach but did not migrate or migrated incompletely to the duodenum, were observed at EM doses above 0.375 mg/kg. Therefore, the optimum dose of EM for inducing an IMC was established to be 0.375 mg/kg. In comparison with spontaneous IMCs, EM-induced IMCs had a significantly longer duration in the stomach and a significantly lower amplitude in the duodenum. These observations indicate that EM induced phase III activity more intensively in the stomach than in the duodenum. The plasma motilin concentration increased significantly during EM induced IMCs, and this suggested a close relationship between this hormone and induction of the IMC. The increase in motilin levels was also observed of the strong gastric contractions which did not migrate or migrated incompletely to the duodenum. Therefore, it seems reasonable to suggest that motilin is involved in phase III activity of the stomach rather than in that of the duodenum. PMID- 8482187 TI - Evaluation of anorectal physiology in patients with increased mast cells. AB - Diarrhea, urgency, and fecal incontinence are common complaints in systemic mastocytosis and in patients with increased gastrointestinal mucosal mast cells. We performed anorectal manometry on six patients with clinical symptoms of mastocytosis and histologic evidence of increased mast cells and compared the results to anorectal manometry of six age- and sex-matched controls, with no bowel symptoms. Standard techniques with balloon volumes were used to measure maximal basal pressure, maximal squeeze pressure, smallest volume sensed, degree of relaxation of the internal sphincter, and the volume causing: (1) a strong urge to defecate and (2) pain. Patients with mastocytosis, compared with controls, had smaller balloon volumes induce rectal urgency (97 vs 164 ml) and pain (117 vs 278 ml). A trend was present for lower maximal basal pressure in mastocytosis, but was not statistically significant. Sensitivity to balloon inflation suggests decreased rectal compliance or overreactive rectal contractility. These findings provide an explanation for the anorectal symptoms in patients with increased mast cells. PMID- 8482188 TI - Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis. AB - Ursodeoxycholic acid has been proposed for the treatment of primary biliary cirrhosis. The aim of this study was to evaluate the effect of ursodeoxycholic acid administration on bile acid metabolism in patients with early-stage primary biliary cirrhosis. Biliary bile acid composition, primary bile acid pool sizes, synthesis, and fractional turnover rate were measured before and after four weeks of ursodeoxycholic acid administration (600 mg/day) in nine patients with biopsy proven primary biliary cirrhosis (stages I-III). Molar percentages of chenodeoxycholic, cholic, and deoxycholic acids in bile were significantly decreased by ursodeoxycholic acid administration, while its biliary concentration increased to 34.2% at the end of the same four-week period. The cholic and chenodeoxycholic acid pools decreased, although not significantly, while the deoxycholic acid pool was reduced by 60% (from 0.7 +/- 0.12 to 0.29 +/- 0.07 mmol, P < 0.002). Primary bile acid synthesis was slightly increased, and fractional turnover rate was significantly increased. The conversion rate of cholic to deoxycholic acid was measured and found to be significantly increased (P < 0.05) after ursodeoxycholic acid administration; however, serum levels of both free and conjugated deoxycholic acid were significantly decreased (from 23.2 +/- 9.7 to 3.8 +/- 1.9 mumol/liter, P < 0.001). We conclude that in patients with primary biliary cirrhosis, ursodeoxycholic acid administration replaces endogenous bile acids in the enterohepatic circulation by increasing bile acid fractional turnover rate without significant increments of their hepatic synthesis. PMID- 8482189 TI - Concentrated ascitic fluid reinfusion after cascade filtration in tense ascites. AB - A new method for concentrated ascitic fluid reinfusion using a double ultrafiltration device is reported as 22 procedures in 20 cirrhotic patients (6 females, 14 males; median age 55 years, range 33-69) with tense, refractory ascites. Eight of the 20 patients had elevated creatinine levels. The mean time for each procedure was 189 +/- 82 min, during which a mean of 7.7 liters (1.3 13.3) of ultrafiltered ascitic fluid was removed and 613 ml (140-1700) of concentrated ascitic fluid rich in albumin (mean: 60 g, range 14-175) was reinfused. The procedure resulted in a mean weight loss of 8.1 kg (2.2-14.0) and a mean increase of 163 ml in urine output (24 hr). A reduction in the serum creatinine level (P < 0.05) and an increase in the plasma atrial natriuretic factor level (P < 0.02) 24 hr after reinfusion, while no changes in serum albumin, plasma and urinary electrolytes, plasma renin activity, aldosterone, and antidiuretic hormone levels were noted. Although minor evidence for a disturbance in coagulation was observed, there were no episodes of clinical bleeding. Four patients (20%) had transient chills or fever. Based upon this experience, it can be concluded that reinfusion of cascade filtered and concentrated ascitic fluid is a rapid, safe, and effective treatment for patients with tense ascites; it appears to have less side effects than more traditional methods and importantly does not require administration of heterologous plasma derivatives. PMID- 8482190 TI - Isolation of mucin from human hepatic bile and its induced effects on precipitation of cholesterol and calcium carbonate in vitro. AB - Biliary mucin was isolated from human hepatic bile, and its induced effects on the appearance time of cholesterol monohydrate crystals (nucleation time) and on the precipitation of calcium carbonate were studied in vitro to examine the possible significance of mucin for ductular gallstone formation. Mucin was isolated by gel filtration on Sepharose CL-4B and a subsequent CsCl density gradient ultracentrifugation. Mucin thus obtained had a high purity as shown by a high-molecular-weight band on SDS-polyacrylamide gel electrophoresis and by the compatible amino acid composition with mucin purified from the gallbladder. The mucin at as low a concentration as 100 micrograms/ml significantly shortened the cholesterol nucleation time in the supersaturated model bile, mimicking human hepatic bile. On the other hand, the addition of mucin inhibited calcium carbonate precipitation in vitro. Taking account of that both cholesterol and calcium salts are major constituents of ductular gallstones, we conclude that biliary mucin is likely to play an important regulating role in the formation of ductular stones. PMID- 8482191 TI - Lactitol in treatment of chronic hepatic encephalopathy. A meta-analysis. AB - The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase deficient patients. The methodological quality of these studies was high. Meta analysis showed that lactitol was as effective as other disaccharides in the treatment of encephalopathy: pooled odds ratio was 0.83, 95% confidence interval was 0.38-1.82. Results were not sensitive to the use of alternative methods of counting and attributing events in these trials. Patients experienced fewer side effects during treatment with lactitol, but the pooled odds ratio was not statistically significant. In all studies lactitol was considered more palatable. Clinical effectiveness of lactitol, in long-term treatment of chronic encephalopathy, is similar to those of lactulose. It seems that lactitol has lower side effects than lactulose. Future RCTs with a double-blind design could be mainly aimed at evaluating the side-effect profile of the two disaccharides. PMID- 8482192 TI - Is chemotherapy associated with development of Barrett's esophagus? AB - Columnar-lined or Barrett's esophagus is a premalignant condition. It is almost unvariably due to chronic gastroesophageal reflux. Since there are some reports that Barrett's esophagus can be induced by chemotherapy, we investigated 20 male patients, treated with chemotherapy for testicular cancer, and 18 female patients, treated with high-dose chemotherapy for breast cancer. Only one patient in the testicular cancer group had Barrett's esophagus of the circumferential type, in addition to typical reflux esophagitis and a hiatal hernia four years after chemotherapy. In the breast cancer group one patient had an indeterminate junction. Our results do not support the hypothesis that chemotherapy poses a substantially increased risk for the development of Barrett's esophagus. PMID- 8482193 TI - Treatment and long-term outcome of chronic radiation esophagitis after radiation therapy for head and neck tumors. A report of 13 cases. AB - The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. We describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2-120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N = 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482194 TI - Serum pepsinogens after interruption of long-term maintenance therapy with omeprazole in patients with reflux esophagitis. AB - Administration of omeprazole induces increases in serum concentrations of pepsinogens A and C. In 10 patients with reflux esophagitis who were on continuous maintenance treatment, the effect of cessation of omeprazole administration on serum pepsinogens was studied. Pepsinogens A and C were measured in serum samples on days 0, 1, 2, 4, 7, and 9 after treatment and the results were compared with the values available in eight patients at a time before omeprazole treatment. Serum pepsinogen A levels decreased gradually after cessation of omeprazole administration, and all values fell into the normal range after the seventh day of the study period, but were still higher than before therapy. Seven of 10 patients showed a decrease of pepsinogen C after nine days, but two patients had still increased levels at the end of the study period. The pepsinogen A:C ratio on the ninth day after cessation was significantly lower than on day 0 during omeprazole therapy. We conclude that long-term maintenance therapy with omeprazole induces significant increases in both serum pepsinogens. After cessation of omeprazole treatment, serum pepsinogens rapidly decrease in most patients, but continue to be higher before therapy for at least nine days. PMID- 8482195 TI - Local cellular and immune response by antral mucosa in patients undergoing treatment for eradication of Helicobacter pylori. AB - Thirty-six patients with nonhealing or recurrent duodenal ulcers (DU) were treated with omeprazole; 20 mg/day for one month followed by triple therapies (metronidazole, 400 mg three times a day, tetracycline, 500 mg four times a day with either colloidal bismuth, 120 mg four times a day or sucralfate 1 g four times a day. At least two gastric mucosal samples were collected from the antral portion of the stomach and from the duodenum before and immediately after omeprazole therapy and four weeks after completion of triple therapies. Samples were fixed in buffered formaldehyde and glutaraldehyde and examined histologically and histochemically for inflammation, density of H. pylori colonization, and immunohistochemically for the density of gastrin-secreting cells, immunoglobulins (IgA, IgG, IgM), kappa and lambda light chains and T lymphocyte population. H. pylori colonization of the antral mucosa before treatment was noted in 100% and active gastritis in 86% of patients. The histologically assessed clearance rate after omeprazole treatment was 47.3%, and after triple therapies, 69.5%. The prevalence of gastritis was observed in 63.9% and 33.3% respectively. All therapies were associated with an accumulation of serous fluid, increased population of lymphocytes and plasma cells, and secretion of immunoglobulins, particularly IgG and IgM in the upper part of the lamina propria. These changes, together with increased numbers of T lymphocytes within the crypt epithelium and the lamina propria, were associated with the presence of H. pylori organisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482196 TI - Ferrous sulfate reduces cimetidine absorption. AB - A variety of drugs that bind to iron have significant reductions in absorption when coadministered with iron compounds. Cimetidine has a structure that would suggest strong binding to iron ions. In vitro experiments were performed to examine a variety of characteristics of the binding of iron to cimetidine. Further studies were conducted to determine the effect of concurrent administration of ferrous sulfate on cimetidine absorption in an in vivo isolated perfused rat jejunal model of drug absorption. The dose of cimetidine was chosen to represent a human dose of 300 mg, while the ferrous sulfate doses were chosen to represent 150- and 300-mg doses. The higher ferrous sulfate dose completely inhibited cimetidine absorption (P < 0.01), while the lower dose of ferrous sulfate caused a 63% reduction in cimetidine absorption (P < 0.05). In vitro iron in its ferrous from rapidly oxidizes to the ferric form. The ferric form of iron binds to cimetidine and may be the cause of the decreased cimetidine absorption. Care should be taken in prescribing iron supplements with cimetidine. PMID- 8482197 TI - Squamous metaplasia of extrahepatic biliary system in an AIDS patient with cryptosporidia and cholangitis. AB - AIDS-related cholangiopathy is an increasingly recognized syndrome associated with significant morbidity and mortality. The mechanism of cholangiopathy is unknown but is assumed to be related to infectious pathogens such as CMV and cryptosporidia. The case of a Haitian with HIV and long-standing intestinal cryptosporidiosis who presented with cholangitis and protuberant intrabiliary filling defects is reported. Histopathological examination of biliary biopsies revealed previously unreported extensive squamous metaplasia of the bile duct epithelium, and the histogenesis of this condition is discussed. Chronic cryptosporidial infestation may be directly pathogenic resulting in squamous metaplasia that mimics biliary malignancy. PMID- 8482198 TI - Idiopathic chronic calcifying pancreatitis with diabetes mellitus. Analysis of pancreatic stone protein gene. AB - We present a case of a 27-year-old female suffering from chronic calcifying pancreatitis with diabetes mellitus. Radiographic examinations and exocrine pancreatic function tests revealed considerable dilatation of pancreatic ducts with large intraductal calculi and exocrine pancreatic insufficiency, respectively. Recent literature indicates that a decrease in the activity of pancreatic stone protein (PSP), which inhibits CaCO3 crystal formation in pancreatic juice, is closely related to the development of chronic calcifying pancreatitis. The patient had no apparent cause or family history of pancreatitis. We therefore investigated the possibility that alterations in the PSP gene might explain the chronic pancreatitis seen in this patient. Six exons of the PSP gene amplified by polymerase chain reaction were directly sequenced, but there was no apparent base mutation observed. Furthermore, Southern blot analysis revealed neither rearrangement nor deletion of the PSP gene in the genomic DNA of this case. However, this genetic approach will be useful for future study of the etiology of hereditary pancreatitis. PMID- 8482199 TI - Esophageal motility impairment in Plummer-Vinson syndrome. Correction by iron treatment. AB - We report the case of a 41-year-old woman with Plummer-Vinson syndrome and an esophageal motility disorder. She complained of dysphagia and odynophagia and had cheilitis, glossitis, and hypochromic anemia. An esophageal motility study showed low amplitude of contraction and high intrabolus pressure in the esophageal body. After iron replacement, the patient was free from symptoms, and a new motility study showed increased amplitude of contraction and decreased intrabolus pressure. PMID- 8482200 TI - Aspiration of bile during laparoscopic cholecystectomy benefits surgeon and investigator. PMID- 8482201 TI - Personality traits and gastric acid secretion in ulcer disease. PMID- 8482202 TI - [Work and health protection of nursing personnel in view of the guidelines of the European community on "lifting and carrying". Empiric study on the current situation and the potential for its shaping]. PMID- 8482203 TI - [Moving bodies in strange places and times]. PMID- 8482204 TI - [Activating care]. PMID- 8482205 TI - [Basal stimulation]. PMID- 8482206 TI - [Kinesthetics in nursing--moving with minimum effort]. PMID- 8482207 TI - [The Feldenkrais method]. PMID- 8482208 TI - [Proper tension and movement]. PMID- 8482209 TI - [Osteopathy]. PMID- 8482211 TI - [School for the back]. PMID- 8482210 TI - [Body building and movement formation--components of health care]. PMID- 8482212 TI - [Bobath's treatment of movement disorders]. PMID- 8482213 TI - [Potentials of physical therapy in cerebral movement coordination disorders in infants and children]. PMID- 8482214 TI - [Vojta's treatment of movement disorders]. PMID- 8482215 TI - [Perspectives of teacher training in nursing. A discussion with Thomas Bals' attempts at normalization]. PMID- 8482216 TI - [Nursing care of patients following liver and kidney transplantation]. PMID- 8482217 TI - [Immunosuppression and prevention of infection in patients with liver and kidney transplantations]. PMID- 8482218 TI - ["From health to disease"--the well person. Theoretical introductory article within the framework of a holistically oriented educational concept--development and implementation]. PMID- 8482219 TI - [The beautiful body]. PMID- 8482220 TI - [Plastic covering of skin and reconstruction of scars after scalds and burns]. PMID- 8482221 TI - [Possibilities of reconstructive plastic surgery]. PMID- 8482222 TI - [Shape changing and reconstructive surgery on the female breast]. PMID- 8482223 TI - [Birthmarks on the skin and their therapy]. PMID- 8482225 TI - [Nursing a child with cleft lip and cleft palate]. PMID- 8482224 TI - [Therapy of cleft lip and cleft palate]. PMID- 8482226 TI - [Carrying out the regulations for the nursing personnel. Utilization of data for the internal organization]. PMID- 8482227 TI - [Cough, head colds, hoarseness]. PMID- 8482228 TI - [The nursing process during nursing education. Legal requirements and reality]. PMID- 8482229 TI - [Accompanying care]. PMID- 8482230 TI - [Endoscopic ultrasound in the demonstration and staging of non-Hodgkin's lymphomas of the stomach]. AB - Nine patients (five women, four men, mean age 64.2 [49-77] years) with histologically confirmed gastric non-Hodgkin lymphoma (NHL) were investigated before starting therapy and during follow up, using endoscopic ultrasound, computer-assisted tomography and conventional ultrasound. Of ten gastric NHL infiltrations, nine were demonstrable using endoscopic ultrasound, three by computed tomography and two with conventional ultrasound. Accurate assessment of the primary tumour stage was possible in six out of eight cases using endoscopic ultrasound, but in none using tomography or conventional ultrasound. Three of these patients had inflammatory changes in enlarged paragastric lymph nodes and five malignant lymphomatous involvement. The latter was demonstrable by endoscopic ultrasound in all cases, by computed tomography in three cases and by conventional ultrasound in two cases. False positive results were obtained in two cases using endoscopic ultrasound and computed tomography. Regression of the tumour and of paragastric lymph nodes on radio-chemotherapy was demonstrable in two cases, and progression in one using endoscopic ultrasound; the other techniques showed progression of extragastric lymphoma involvement in only one case. Endoscopic ultrasound is an efficient method for demonstration and local staging of gastric non-Hodgkin lymphomas. PMID- 8482231 TI - [The benefits and risks of percutaneous transhepatic cholangioscopy]. AB - Percutaneous transhepatic cholangioscopy (PTCS) was undertaken in 101 patients (for diagnostic reasons in 64 and/or therapeutic reasons in 56) out of 167 consecutive patients (56 women, 45 men; mean age 64.2 [27-95] years) in whom percutaneous transhepatic drainage had been instituted. In all but one of 64 patients PTCS clearly defined stenoses which had been unclear in the cholangiogram. There was a 90% accuracy of histological diagnosis of biopsies obtained under vision in 60 cases. A malignant stenosis was seen in 19 of 25 cases (sensitivity 76%). Severe stenosis, not passable by contrast medium, were recanalized cholangioscopically in 14 of 15 cases. Biliary tract stones were completely removed by PTCS in 40 of 41 patients, by mechanical means (n = 4) or intracorporeal lithotripsy (n = 37). There were no complications from PTCS. It is concluded that PTCS can be performed safely and reliably in patients with functioning percutaneous transhepatic drainage. It provides the diagnosis of previously unclear cholangiographic findings as well as treatment of difficult biliary tract stenoses and/or ductal stones. PMID- 8482232 TI - [The thrombolysis of a septic portal vein thrombosis with ultrahigh-dosage streptokinase]. AB - Eight days after an appendicectomy a 40-year-old man developed a fever of up to 40.5 degrees C. The concentration of the transaminases was elevated (GOT 61 U/l, GPT 115 U/l, gamma-GT 226 U/l). Operative revision discovered no unusual wound conditions. Ultrasonography revealed splenomegaly (15 x 7 cm) and dilatation of the portal vein (diameter of 19 mm). The portal vein contained echo-dense constituents indicating thrombosis. Colour Doppler duplex sonography recorded only minimal residual flow around the thrombus. The fever gradually subsided under antibiotic treatment (metronidazole, 500 mg twice daily; mezlocillin, 2 g three times daily; later also gentamicin, 80 mg three times daily). Blood culture grew Bacteroides fragilis. 14 days after the wound revision ultra-high short-term lysis with streptokinase was instituted (9 mill IU over 6 hours), followed by heparin i.v. 25,000-30,000 i.v. daily for 5 days. 12 hours after the start of thrombolysis treatment the portal vein thrombus had been dissolved, and after 8 days the size of the spleen was normal. PMID- 8482233 TI - [The fundamentals of gene technology]. PMID- 8482235 TI - [Why is there a type-2 diabetes?]. PMID- 8482234 TI - [Abdominal obesity. The metabolic syndrome, arteriosclerosis and mortality]. PMID- 8482236 TI - [Parenteral vitamin K prophylaxis and the cancer risk]. PMID- 8482237 TI - [The treatment of acromegaly with octreotide]. PMID- 8482238 TI - [The long-term success after coronary angioplasty in old age]. AB - Long-term results of coronary angioplasty (CAP) were compared between two age groups of patients. Group 1 had 227 patients (158 men, 69 women) with a mean age of 70 (65-88) years, group 2 had 717 patients (611 men, 106 women), mean age 54 (20-64) years. Unstable angina was more common in group 1 than group 2 (48.9 vs 37.7%, P < 0.05). Multi-vessel disease was present in 50.7% of those in group 1 and 41.9% in group 2. Primary success of CAP was similar in the two groups (group 1: 88.1%, group 2: 90.5%). The long-term effect at the first follow-up angiography 3-4 months after CAP was slightly less favourable in group 1 than 2 (54.9 vs 58.3%; difference not significant). However, there were more patients with unstable angina in group 1. Thus the angiographic long-term results were worse in the older patients (44.6 vs 60.1%; P < 0.05), while there was no difference between the two groups as regards stable angina (64.7 vs 57.2%). After a second CAP (because of recurrence), the long-term angiographic effect was, if anything, slightly better in the older patients (87.0 vs 77.1%). The death-rate (cardiac causes of death) up to one year after CAP was comparable in the two groups (1.7 vs 0.8%), as was the rate of non-fatal myocardial infarction (2.2 vs 1.3%). These data indicate that clinical and angiographic long-term success after CAP is comparable in older and younger patient groups and age alone does not present a higher risk. PMID- 8482239 TI - [Acute myoglobinuric kidney failure in McArdle's syndrome. The diagnostic significance of 31P nuclear magnetic resonance spectroscopy]. AB - A 44-year-old man developed acute renal failure, associated with reddish brown urine, after severe physical exertion. Since childhood his physical capacity was known to be limited. Muscular indurations, cramps and pains had occurred after muscular work. Serum creatinine level on the day before hospitalization was 10.0 mg/dl, creatine-kinase activity 3,790 U/l, lactate dehydrogenase activity 670 U/l, myoglobin level 701 ng/ml. Cause of the rhabdomyolysis was thought to be McArdle's disease (glycogen storage disease type V: abnormal skeletal muscle glycogen utilization). 31P-magnetic resonance spectroscopy, which gives characteristic spectra with anaerobic muscle work, provided the diagnosis, which was confirmed by measurement of myophosphorylase activity in a muscle biopsy (zero activity). After two dialysis sessions and alkalinization of the urine diuresis again occurred and the retention indicators fell to normal in the course of the subsequent 18 months. Creatinine kinase activity remained elevated. PMID- 8482240 TI - [Chronic ethylene glycol poisoning]. AB - Over a six-week period a 60-year-old patient had several unexplained intoxication like episodes. He finally had severe abdominal cramps with changes in the level of consciousness and oligoanuric renal failure (creatinine 4.7 mg/dl). The history, marked metabolic acidosis (pH 7.15, HCO3- 2.2 mmol/l, pCO2 6.6 mmHg) as well as raised anion residue (43 mmol/l) and the presence of oxalates in urine suggested poisoning by ethylene glycol contained in antifreeze liquid. Intensive haemodialysis adequately eliminated ethylene glycol and its toxic metabolites (glycol aldehyde, glycolic acid). Renal function returned within 10 days, although the concentrating power of the kidney remained impaired for several weeks because of interstitial nephritis. The intoxication had been caused by a defective heating-pipe system from which the antifreeze had leaked into the hot water boiler (the patient had habitually prepared hot drinks by using water from the hot-water tap). Gas chromatography demonstrated an ethylene glycol concentration of 21 g per litre of water. PMID- 8482241 TI - [Multimodal therapy concepts in esophageal carcinoma]. PMID- 8482242 TI - [The warning of a chief physician against breach of the service regulations. The judgement of the Kempten Labor Court of 6 August 1992]. PMID- 8482243 TI - [Spring fatigue?]. PMID- 8482244 TI - [Anticoagulation in ischemic cerebral infarct?]. PMID- 8482245 TI - [Regional hyperthermic fibrinolytic perfusion]. PMID- 8482246 TI - [The fibronectin content of the bile]. PMID- 8482247 TI - [The late results following heart transplantation]. PMID- 8482248 TI - The increasing importance of allergy. PMID- 8482249 TI - Osteomas of the external auditory canal. PMID- 8482250 TI - Gastroesophageal reflux laryngitis. PMID- 8482251 TI - Allergic arthritis. PMID- 8482252 TI - Sudden cardiac arrest during adenotonsillectomy in a patient with subclinical Duchenne's muscular dystrophy. AB - We describe a four-year-old boy of Indian descent who had elective adenotonsillectomy for chronic sore throat and partial airway obstruction. About 10 minutes into the procedure, the patient suddenly developed cardiac asystole. After prolonged cardiac resuscitation, recovery was achieved. No permanent neurologic deficits resulted. The child was later found to have a strong family history of Duchenne's muscular dystrophy (DMD) and an elevated serum creatine kinase level documented since shortly after birth. We reviewed several case reports substantiating the risk for cardiac arrest during general anesthesia in DMD patients, and we concluded that DMD is a little-known risk for cardiac arrest during general anesthesia. The otolaryngologist must be aware of this potential complication, because tonsillectomy and adenoidectomy are commonly indicated for children at an age when DMD may be subclinical. PMID- 8482253 TI - Indirect microsurgery of the vocal folds--videostroboscopy vs. microstroboscopy. AB - In spite of the great significance of direct microlaryngeal surgery (DML), the inadequacies of this technique are evident. In order to avoid surgical trauma and introduce functional control during surgery, indirect microstroboscopic (IMS) and indirect videostroboscopic surgery (IVS) of the vocal folds are advocated. Both of these meet most criteria for surgical work in this field. The aim of this work was to make a comparative study of these techniques. The study is based on 603 operations conducted for benign lesions of the vocal folds. We are of the opinion that indirect vocal fold surgery for small benign lesions has significant advantages when compared with the conventional microlaryngoscopy, including laser surgery, which was proven elsewhere. When comparing these two indirect surgical approaches, the principal advantages of IVS surgery over the IMS method are easier surgical manipulation and better view. With respect to other areas of comparison, these techniques are quite similar. As complementary methods to conventional microlaryngoscopy, we believe that both IVS and IMS surgery should be used in practice. PMID- 8482254 TI - Functional parathyroid cyst and hypocalciuric hypercalcemia. AB - Parathyroid cysts are uncommon. They can be divided into functional and nonfunctional cysts depending on whether or not they are associated with hypercalcemia. Functioning cysts are very rare with less than twenty reported cases. We report a case of functioning parathyroid cyst associated with hypocalciuric hypercalcemia. We have been unable to find a similar case previously reported in the literature. PMID- 8482255 TI - The use of Merocel for temporary medialization of the middle turbinate during functional endoscopic sinus surgery. PMID- 8482256 TI - Pharyngeal pouch carcinoma. AB - Malignant change occurs in 0.3-10% of pharyngeal pouches, with longstanding pouches most at risk. Contrast radiology and endoscopy can detect large and medium sized tumors but are inadequate for small lesions and carcinoma in situ. Expectant treatment and conservative surgery fail to provide an excised pouch for histological analysis and small lesions may be missed. Consequently, careful consideration must be given to radical excision, particularly if the pouch has been longstanding. The role of radiotherapy in conjunction with surgery remains unproven. PMID- 8482257 TI - Can Rinne's test quantify hearing loss? PMID- 8482258 TI - Evaluating the lease vs. purchase decision. AB - Each individual lease vs. purchase situation should be analyzed using the Net Present Value evaluation Method proposed to decide which method of financing is best for a particular practice. As this article is not designed to be a comprehensive resource on lease vs. purchase decision making, it is hoped that this model can be a starting point for you and your financial manager to develop a NPV/lease vs. purchase model that is more relevant to your practice. PMID- 8482259 TI - Training in tympanoplasty. PMID- 8482260 TI - Serous otitis media. PMID- 8482261 TI - Vocal fold varicosities. PMID- 8482262 TI - Staging in cholesteatoma surgery. AB - The closed technique is the treatment of choice for middle ear cholesteatoma in the opinion of the author. Several interventions may be required. At the onset, the purpose of the systematic second stage procedure was to verify the absence of any residual cholesteatoma. Experience has shown that the interest of this second intervention lies equally in the opportunity to observe the evolution of the otitis disease process, and the tubal status and in the possibility of restoring transmission under optimal conditions, thanks in particular to the utilization of thick silastic sheeting. This technique necessitates, however, a long-term follow up. On occasion, a third intervention may be required. Despite the iterative nature of this surgery, it should be considered as a form of a logical progression offering the best chances of a successful anatomic and functional outcome for the patient. PMID- 8482263 TI - Findings in revision myringoplasty. AB - Findings in 38 revision myringoplasty operations were studied. Fascial grafts were used in all operations. The majority of immediate failures after primary procedures were found to be consequences of technical faults, i.e. poor anterior adaptation of the graft. Most of the late re-perforations were caused by atrophy of the graft without infection. The success rate for revision myringoplasty did not differ significantly from that for primary operations. It was concluded that better surgical techniques and better graft materials should be developed. PMID- 8482264 TI - Predominance of left ear in Meniere's disease, sudden deafness, inner ear damage, tinnitus and abnormally patent eustachian tube. PMID- 8482265 TI - The role of retraction pockets in cholesteatoma development: an ultrastructural study. AB - Persistent retraction pockets causes erosion by adhering to ossicles and other structures of the middle ear. These are characterized by lysis of fibrous layer. Being in contact the squamous epithelium and the middle ear mucosa, it comprises the precursor mechanism of cholesteatoma. The present study discards the classical theories assuming epithelial migration through marginal or attic perforation; and demonstrates that these secondarily develop as a result of cholesteatoma. Retraction pocket specimens obtained from 10 cases of adhesive otitis media were examined with light and transmission electron microscopy and the presence of papillary ingrowth of the squamous epithelium was demonstrated. PMID- 8482266 TI - Future directions in sleep research: a respiratory physician's perspective. PMID- 8482267 TI - Squamous cell carcinoma of the nasal septum mucosa. AB - Primary squamous cell carcinomas of the nasal septum constitute only 9% of all malignant tumors of the nasal cavity. We present 16 cases occurring during a 14 year period. As the initial signs of these carcinomas are no different from non neoplastic disease, a high index of suspicion is necessary in order to correctly diagnose these lesions. It seems to us that when the diagnosis of nasal septum carcinoma is established, the best method of treatment is wide surgical excision and immediate repair of the defect by a split-skin graft. PMID- 8482268 TI - A communication from the People's Republic of China: management of labyrinthine fistula with cholesteatoma. AB - Management and results in 43 cases of labyrinthine fistula with cholesteatoma are presented and discussed. The choice of surgical procedure is based on the presence or absence of infection; the size and location of the fistula; condition of the other ear; cochlear function, and condition of the stapes. Unchanged bone conduction has been obtained in 88% of our 43 surgical cases. The planned staged operation has produced good functional results. PMID- 8482269 TI - Treatment of otorrhea associated with tubes or perforations. PMID- 8482270 TI - Special drug communication teleconference. PMID- 8482271 TI - William McKim Marriott (1885-1936). PMID- 8482272 TI - Retinopathy of prematurity--current diagnosis and management. AB - Despite advances in ophthalmological care of premature infants, retinopathy of prematurity (ROP) remains a still unsolved problem for paediatricians as well as ophthalmologists. A survey of the current literature concerning drug therapy and surgical management as related to the different stages of ROP is given. The classification system for ROP according to the International Committee is presented as well as our screening policy in relation to the literature. The effectiveness in preventing severe cases of ROP and the toxicity of vitamin E supplementation in high-risk premature infants is still disputed and no recommendations can be given. Cryotherapy is recommended in symmetric cases of stage 3 + ROP. Nevertheless, quite a number of eyes still progress to more severe stages of ROP. Scleral buckling procedures and vitrectomy may lead to anatomical success in a few cases of retinal detachment, however, the visual outcome of such an operation is usually very poor despite reattachment of the central retina. PMID- 8482273 TI - Phytophotodermatitis mimicking child abuse. AB - A 13-month-old girl presented with red finger marks on both shoulders thought initially to be secondary to child abuse. The appearance of the marks was not typical of bruising of the stated age and there were no social concerns or other medical features of child abuse. Direct questioning revealed that the mother had been gardening on a sunny day and had picked the child up prior to the appearance of the marks. The marks are thought to represent a phytophotodermatitis. Many paediatric skin conditions can mimic child abuse. Recognition of this further possibility will prevent avoidable errors of diagnosis. PMID- 8482274 TI - Does constitutional delayed puberty cause segmental disproportion and short stature? AB - We have reviewed the growth of 98 boys and 34 girls with constitutional delay of growth and puberty followed until final height. At presentation chronological age was 14.1 (1.3) years (SD) in the boys and 13.0 (1.3) years in the girls. At presentation all patients were either prepubertal or in early pubertal maturation (4 ml testicular volume in the boys and breast stage II in the girls). Twenty nine boys (30%) and 2 girls (6%) were treated with either sex or anabolic steroids. Mean height SDS in the boys at presentation was -2.7 (0.7) which rose to -1.9 (0.9) at final height attainment. This was significantly lower than the predicted final height SDS of -1.4 (0.8) and mid-parental height SDS of -0.5 (0.7). Similar results were obtained for the girls with a height SDS at presentation of -3.2 (0.8) which increased to -2.3 (0.7) at final height which was significantly lower than predicted final height SDS of -1.7 (0.6) and mid parental height SDS of -0.8 (0.8). Both sexes had a relatively short sitting height at presentation; sitting height SDS -3.4 (1.0) and subischial leg length SDS -2.2 (1.0) in the boys and sitting height SDS -3.6 (1.1) and subischial leg length SDS -2.5 (0.7) in the girls. The relative disproportion between the segments had no significant change at final height. We are unable to explain the failure to achieve final height potential and the relatively disproportionate stature. Our data suggest that the late timing of the onset of puberty may be deleterious to spinal growth and consequently final height.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482275 TI - The long-term effect of cyproterone acetate on growth in girls with idiopathic precocious puberty. Androcur Study Group in Japan. AB - To define the effect of cyproterone acetate (CPA) on statural growth, 25 girls with idiopathic precocious puberty who had been treated with CPA were studied retrospectively. The final height SDS was -1.12 +/- 1.16 (mean +/- SD). The daily CPA dose was negatively related to the final height SDS. We divided our subjects into two groups according to the daily CPA dose [low dose, 84.9 +/- 15.4 mg/m2 (n = 19) vs high dose, 135.8 +/- 17.1 mg/m2 (n = 6)]. In the low dose group, the difference of the final height SDS minus height SDS for bone age at the initiation of CPA treatment was 0.55 +/- 1.16 and final height SDS was -0.82 +/- 1.05. The final height was not significantly different from the target height in the low dose group subjects whose target heights were obtained. Since the increment of height age to the increment of bone age during the treatment was significantly less in the group needing and treated with high dose CPA, high doses of CPA may reduce growth velocity more than its suppressive effect on bone maturation. These results suggest that CPA has an effect on statural growth in girls whose clinical symptoms can be controlled with a low dose of CPA, although they have not been compared with final height in untreated Japanese girls. PMID- 8482276 TI - Clinical settings and vasopressin function in hyponatraemic children. AB - Hyponatraemia is one of the most common electrolyte abnormalities in hospitalised children. In a prospective study we tested whether hyponatraemia is associated with sustained release of the antidiuretic hormone arginine vasopressin (AVP). Out of 27 children with persistent hyponatremia (serum sodium < 130 mmol/l), 25 had measurable plasma concentrations of AVP [median and quartiles 5.0 pg/ml (1.5 8.3)]. Volume contraction as consequence of sodium loss caused hyponatraemia in 16 patients. Hyponatraemia in the presence of extracellular volume expansion and reduced effective arterial blood volume occurred in 5 patients. Only 3 patients had normovolaemic hyponatraemia (so-called syndrome of inappropriate antidiuretic hormone secretion) and 3 suffered from chronic renal failure. It is concluded that plasma AVP concentration is measurable in most children with hyponatraemia. Non-osmotic stimulation of AVP release and lack of suppression of this hormone is an important pathogenetic mechanism of hyponatraemia in children. PMID- 8482277 TI - A regional experience of red cell aplasia. AB - The incidence and current management of red cell aplasia in children was determined from a retrospective survey of haematologists and paediatricians in the northern health region of England over a 7-year period. Thirty-three children were diagnosed: 4 had Diamond Blackfan anaemia, 22 transient erythroblastopenia of childhood, and 7 parvovirus B19 aplasia, with annual incidences of 1, 5 and 2 per 1,000,000 children respectively. Many were over-investigated. Three with Diamond Blackfan anaemia were steroid responsive. One with transient erythroblastopenia was retrospectively diagnosed because anaemia did not recur after steroids were stopped. Transient erythroblastopenia is the most common single cause of red cell aplasia in immunocompetent children. Time, observation and bone marrow examination before steroid therapy are the ways to distinguish transient erythroblastopenia from Diamond Blackfan anaemia or leukaemia. Interpretation of red cell indices using age-related percentiles may reduce the number of inappropriate investigations of the anaemia, but is often unhelpful in distinguishing the various causes of red cell aplasia. PMID- 8482278 TI - Cytokines predict coronary aneurysm formation in Kawasaki disease patients. AB - In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor alpha (TNF-alpha) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL 6, IL-8, sIL-2R and TNF alpha were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF alpha. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P < 0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P < 0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF alpha were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF alpha were significantly higher in the patients with than in those without coronary aneurysm (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482279 TI - A Japanese family of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy. AB - Three cases of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy are described from one related Japanese kindred. Two boys had died due to severe diarrhoea accompanied by total or subtotal intestinal villous atrophy. In contrast, although one patient showed the same symptoms and had circulating IgG antibodies against enterocytes, his condition improved dramatically and he developed well following the use of cyclosporin A (CSA). CSA may be beneficial in patients with this rare disorder. Auto-immune enteropathy should be considered as a cause of protracted diarrhoea with unknown aetiology. PMID- 8482280 TI - Unmasking of latent hypoparathyroidism in a child with partial DiGeorge syndrome by ethylenediaminetetraacetic acid infusion. AB - DiGeorge syndrome is a rare congenital anomaly with a wide range of clinical manifestations. This syndrome is usually associated with hypocalcaemia resulting from primary hypoparathyroidism. We report here a case of an 8-year-old boy with partial DiGeorge syndrome who presented initially with neonatal hypocalcaemia, but was subsequently normocalcaemic. Latent hypoparathyroidism was unmasked by a diagnostic EDTA infusion resulting in hypocalcaemia without a parathyroid hormone response. We propose that EDTA infusions can be useful in the diagnosis of latent hypoparathyroidism in children. PMID- 8482281 TI - Heterogeneity of Clostridium difficile isolates from infants. AB - In order to improve our understanding of the role of Clostridium difficile in infants we characterised the strains isolated from this population. The production of toxin A and toxin B was studied. The toxin A, playing a major role in the disease, was searched for in faecal samples. The serogroup of the isolates was determined because some serogroups have been shown to be more pathogenic than others. Over a 9-month period, 102 faecal samples from 102 hospitalised infants (0-12 months) were analysed and 26% of the children were colonised with C. difficile. Fifteen isolates secreted neither toxin A nor B (62.5%). Nine isolates were toxigenic and secreted both toxins (37.5%). Of the eight toxigenic strains tested, six were from serogroup H and two serogroup K. Of the 13 nontoxigenic strains tested, 8 belonged to serogroup D, 2 to serogroup X, and 1 each to serogroup A, serogroup B and serogroup C. Three infants out of 102 studied had toxin A in their faeces. In summary, the infants can be colonised by (1) nontoxigenic strains, most of them from nonpathogenic serogroup D, without toxin A in the faeces; (2) toxigenic strains of virulent serogroups H and K, with or without toxin A in the faeces. Although some infants had diarrhoea, none needed a specific treatment for C. difficile. No specific C. difficile pathology could be retained and different mechanisms are advanced to explain this absence of pathogenicity. PMID- 8482282 TI - Acute endocarditis following pneumococcal meningitis. AB - Acute mitral valve endocarditis, presenting as a new murmur and haematuria, complicated pneumococcal meningitis in a 20-month-old child with a normal heart. Awareness of this rare complication of pneumococcaemia and its early diagnosis, using cross-sectional echocardiography, improves the clinical outcome of a condition associated with a high mortality. PMID- 8482283 TI - Bacterial-induced activation of erythrocyte T-antigen complicating necrotising enterocolitis: a case report. AB - Erythrocyte Thomsen-Friedenreich crypt antigen (T-antigen) activation is not an uncommon event in infants with severe necrotising enterocolitis (NEC). Transfusion of these infants with blood products containing plasma carries the risk of causing intravascular haemolysis. T-antigen activation is easily detected using a rapid simple lectin agglutination test. Early recognition of T-antigen activation ensures the correct choice of plasma free transfusion therapy. We describe an infant with severe NEC complicated by T-antigen activation and haemolysis. PMID- 8482284 TI - Campomelic dysplasia--an underdiagnosed condition? AB - Campomelic dysplasia (CD) is a rare skeletal dysplasia. The incidence, reported in the literature, is 0.05-0.09 per 10,000 live births. During the period December 1985-December 1990 there were 18,350 live births with 4 cases of CD at Aker University Hospital in Oslo, Norway. This gives an incidence of CD in our observation period of 2.2 per 10,000. Eliminating our first case, because of Pakistani decent, the total incidence is 1.6 per 10,000 among Norwegian infants which is much higher than the incidence previously mentioned. Perhaps CD is under reported and a high proportion of patients remain undiagnosed. We present four cases and discuss the incidence. PMID- 8482285 TI - Carnitine palmitoyl transferase I deficiency presenting as a Reye-like syndrome without hypoglycaemia. AB - An apparently healthy girl aged 2 years 9 months developed a coma with hepatomegaly within 24 h after an influenza-like infection. Plasma glucose and urinary organic acid profile were normal but plasma and urinary carnitine concentrations were increased. Despite symptomatic therapy, she died 11 days later. Oxidation of [1-14C] palmitic acid in the patient's fibroblasts was severely decreased (13% of controls). Further investigations revealed a deficiency of carnitine palmitoyl transferase I (CPT I) in the patient's fibroblasts (15% of controls) whereas CPT II activity was normal. Only four patients with CPT I deficiency have been reported so far. The subtle clinical and biochemical presentation of this disorder, which may account for the small number of cases diagnosed, is discussed. PMID- 8482286 TI - Isolated defect of peroxisomal beta-oxidation in a 16-year-old patient. AB - We describe a 16-year-old boy suffering from psychomotor retardation, sensorineuronal hearing impairment, peripheral neuropathy, hepatosplenomegaly, short stature and delayed puberty. Postnatally, muscular hypotonia, mild facial dysmorphism and delayed fontanelle closure had been noticed. At the time of our examination, adrenal cortical function was normal. Biochemical analysis revealed accumulation of very long (> C22) chain fatty acids in plasma and fibroblasts. Furthermore, elevated levels of intermediates of bile acid synthesis and phytanic acid were detectable. These findings are consistent with a defect in the peroxisomal beta-oxidation system. A generalised defect of peroxisomal function was excluded by normal plasmalogen levels in erythrocytes and normal plasmalogen de novo synthesis in fibroblasts. Immunoblotting of the peroxisomal beta oxidation enzymes gave normal results suggesting retained immunoreactivity but catalytic inactivity of one of the enzymes involved, probably either the trifunctional protein or the peroxisomal ketothiolase. This case markedly differs clinically from the few published reports on isolated deficiencies of peroxisomal beta-oxidation. Among the patients with comparable biochemical findings, this is the first report of survival into adolescence. PMID- 8482287 TI - Glucose metabolism in a term infant with transient hyperinsulinism and high carbohydrate intake. AB - Transient hyperinsulinaemia is a well-known cause of hypoglycaemia in newborn infants. The hypoglycaemia may be caused by a decreased glucose production and/or an increased glucose uptake. Whether the increased uptake is caused by increased glucose oxidation or increased non-oxidative disposal is not known. The aim of this study was to investigate the fate of the large amount of glucose infused in a term infant who developed hypoglycaemia due to transient hyperinsulinaemia shortly after birth and was treated with high glucose infusions. On day 6 an indirect calorimetry study was performed, together with a glucose turnover study. Carbohydrate intake was 13.6 mg/kg per minute (19.6 g/kg per day). Both studies were repeated on day 11, when carbohydrate intake was normalised to 7.8 mg/kg per minute (11.2 g/kg per day). Glucose oxidation was 28% higher and non-oxidative glucose disposal was 257% higher on day 6 as compared to day 11. Our results indicate that hypoglycaemia during hyperinsulinism is the result of increased non oxidative disposal of glucose and not increased glucose oxidation. The results indicate a remarkable capacity of the newborn for lipogenesis during high carbohydrate intake. PMID- 8482288 TI - Non-specific elevation of immunoreactive trypsinogen in sick infants. AB - To determine the effect of neonatal illness on immunoreactive trypsinogen (IRT) levels, the IRT values obtained in sick infants transferred to a neonatal intensive care ward were compared with those found in matched controls. IRT levels from dried blood spots collected on day 4-5 of life from 372 sick infants had a mean value of 0.095 log transformed multiples of the median, whilst controls had a mean of -0.013: a highly significant difference. Classification of the sick infants into principal diagnostic categories failed to show any group contributing disproportionately to the observation. In particular, the level of elevation observed in 33 infants with gut abnormalities such as bowel obstruction, duodenal atresia, exomphalos and gastroschisis, in which some degree of pancreatic obstruction might be expected, was not greater than in other hospitalised infants. These data show that sick infants are at increased risk of being identified by an IRT screening programme aimed at detecting infants with cystic fibrosis. PMID- 8482289 TI - Determinants of oxygenation during high frequency oscillation. AB - Two studies are reported in which the aim was to assess whether oxygenation on transfer to or during high frequency oscillation (HFO) was influenced by the mean airway pressure (MAP) level. Sixteen infants, median gestational age 28 weeks, were recruited into the first study and 14 with a median gestational age of 29 weeks into the second. In the initial study, blood gases were measured immediately before and 30 min after transfer to HFO and comparison made of those infants in whom oxygenation did or did not improve. In the second study the infants were studied at two MAP levels, 2 and 5 cmH2O, above that used during conventional ventilation (baseline MAP) and at two frequencies (10 and 15 Hz), arterial blood gases were measured after 20 min on each setting. In the initial study, on transfer to HFO, oxygenation improved by a median of 21 mmHg in eight infants, but was either unchanged or deteriorated (n = 7) in the other eight infants, the median impairment in oxygenation was by 17 mmHg. The infants in whom oxygenation improved had required a significantly higher MAP during conventional ventilation than the rest of the study group. In the second study, increasing the MAP from 2 to 5 cmH2O above baseline resulted in a significant increase in oxygenation, which was significantly greater at 10 rather than 15Hz. Infants whose MAP remained below 13 cmH2O had impaired oxygenation during HFO compared to that experienced during conventional ventilation. The results of these two studies demonstrate that the MAP level during HFO is an important determinant of oxygenation. PMID- 8482290 TI - Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft fur Padiatrische Nephrologie. AB - Two regimens of steroid treatment for the initial attack of idiopathic nephrotic syndrome (NS) in children were compared in a controlled prospective multi-centre study. Long prednisone therapy consisted of 60 mg/m2 per 24 h for 6 weeks, followed by alternate day 40 mg/m2 per 48 h for 6 weeks. The standard prednisone therapy was 60 mg/m2 per 24 h for 4 weeks, followed by 40 mg/m2 per 48 h for 4 weeks. A total of 71 children with an initial attack of idiopathic NS were allocated at random to the two groups. The cumulative rate of patients with sustained remissions after 2 years was significantly higher after the long course than after the standard treatment (49% vs 19%, P = 0.0079). The mean relapse rate per patient at intervals of 3, 6 and 12 months was lower in the long-course prednisone group than in the standard prednisone group, and the proportion of children with frequent relapses during any subsequent 6 months period was lower in the long-course group than in the standard group (29% vs 57%, P = 0.03). Mild side-effects of corticosteroid therapy were observed more frequently after long course prednisone treatment. It is concluded that long-course prednisone therapy of the initial attack of steroid responsive NS is preferable to the standard regimen because it reduces the rate of subsequent relapses without increasing the risk for severe steroidal side-effects. PMID- 8482291 TI - Qualitative changes in general movements and their prognostic value in preterm infants. AB - Qualitative assessments of general movements have been shown to have considerable power in predicting neurological outcomes in preterm infants with brain damage. In the present study such assessments were made in 35 preterm infants without major neurological problems before term age, born between 27 and 34 weeks gestation, of whom 12 were small-for-gestational-age (SGA). Most infants maintained a normal or (mildly) abnormal quality from 35 weeks postmenstrual age through 6, 12, 18 to 24 weeks corrected age. Seven changed from initially abnormal movements to a normal quality, six of them after 12 weeks. Differences between SGA and appropriate-for-gestational-age infants became less evident with age, particularly after 12 weeks. This was not the case when comparisons were made on the basis of gestational ages below or above 32 weeks. The prediction of neurological and mental outcomes at 1 year also improved after 12 weeks, around which age a major transformation in neural functions occurs. It is concluded that assessments of movement quality are particularly successful in predicting abnormal outcomes in comparison to examinations based on muscle tone and elicited responses. PMID- 8482292 TI - Sibling cases of a degenerative neurological disease associated with hypocupraemia and hypobetalipoproteinaemia. AB - We describe two siblings, a boy and his younger sister, with degenerative neurological disturbances, hypocupraemia and hypobetalipoproteinaemia. The neurological features in both cases were developmental delay, dysarthria, hyperkinetics with an attention deficit, dysdiadochokinesis, night blindness, myoclonic jerks and convulsions. Their serum cooper levels did not increase despite administration of copper sulphate both orally or intravenously. The copper contents of the cultured fibroblasts in the patients were 1.5-fold that of controls. Although neurological disorders associated with abnormal copper metabolism and inherited in an X-linked manner have been previously reported, this is the first report of a neurodegenerative disease concurrent with abnormal copper metabolism and hypobetalipoproteinaemia. PMID- 8482293 TI - Intravenous immunoglobulin in two children with Guillain-Barre syndrome. AB - Two children with Guillain-Barre syndrome were successfully treated with high dose intravenous immunoglobulin (IVIG) and no relapses occurred over a 1 year follow up. No side-effects were observed. These data provide further evidence that IVIG may be safely and effectively employed in children with Guillain-Barre syndrome. PMID- 8482294 TI - The cost associated with intraperitoneal versus subcutaneous administration of erythropoietin. PMID- 8482295 TI - Ethnic differences in Helicobacter pylori infection. PMID- 8482296 TI - 3-Methylglutaconic aciduria in a patient with Pearson syndrome. PMID- 8482297 TI - Acute sensorineural deafness following herpes simplex infection. PMID- 8482298 TI - Pseudohyperkalaemia in Kawasaki disease. PMID- 8482299 TI - Hyponatraemia in "water babies": an underestimated problem? PMID- 8482300 TI - The synergistic effect of trauma and infection on interleukin-1 but not tumor necrosis factor liberation during posttraumatic gram-negative septicemia. AB - The release profiles of interleukin 1 (Il-1) and tumor necrosis factor (TNF) were studied during experimental Escherichia coli septicemia and peritonitis with and without a preceding (-48 h) moderate trauma (femur marrow nailing). The trauma alone did not induce significant Il-1 or TNF liberation to plasma. During septicemia, a rapid IL-1-rise (+30 min) and subsequent normalization (+120 min) was seen. A previous trauma delayed (30 min), but accentuated (2x) and prolonged (> 4 h) the Il-1 response. During peritonitis, a delayed (30 min) but otherwise similar Il-1-response was observed. TNF levels rose rapidly (+30 min) in all animals, and remained high throughout the experimental period (6 h). The trauma did not influence the TNF response. We conclude that a synergism exists between trauma and infection with regard to the magnitude of the Il-1 response. PMID- 8482301 TI - The role of bile and bile acids in bacterial translocation in obstructive jaundice in rats. AB - Male Sprague-Dawley rats were randomly divided into five groups in which group 1 received a sham operation (controls), groups 2-5 underwent common bile duct ligation and transection 14 days before the experiments. Two days prior to the studies, animals in groups 1 and 2 received saline orally, while groups 3-5 received an oral administration of either cholic acid, deoxycholic acid or whole bile. Specimens were taken for bacterial culture, and blood was collected for endotoxin assay. The rate of positive bacterial cultures from mesenteric lymph nodes in jaundiced saline-treated animals was significantly higher (p < 0.05) as compared with both controls and the other jaundiced animals treated with either bile or bile acids. Assays were positive for endotoxin in the jaundiced saline treated group, whereas they were negative in both controls and bile- or bile-acid treated animals. We conclude that oral administration of cholic acid, deoxycholic acid or whole bile inhibited bacterial translocation and endotoxin absorption in obstructive jaundice in the rat. PMID- 8482302 TI - Feline intestinal ischemia and reperfusion: relation between radical formation and tissue damage. AB - Experimental ischemia of 15, 30, or 60 min length, followed by 30 min of reperfusion, was produced in situ in the cat small intestine by means of an adjustable arterial clamp. Arterial perfusion pressure was lowered to such an extent that intestinal blood flow decreased from about 25 to 3.5 ml x min-1 x 100 g-1. The rate of free radical formation was followed intermittently with ESR and a modified spin trapping technique in the control period prior to ischemia and at various times during reperfusion. Upon reperfusion radical formation increased above the preischemic control value in all three series of experiments. Cumulative radical production during the 30 min reperfusion period rose from about 3 mumol x 100 g-1 after 15 min ischemia to approximately 4.5 mumol x 100 g 1 after 30 min and 8-10 mumol x 100 g-1 after 60 or 120 min ischemia. At the same time mucosal damage became more pronounced, suggesting a causal connection between tissue damage and radical formation. More specifically, radical production was strongly correlated to histological damage occurring during reperfusion as seen when comparing radical production in animals not experiencing reperfusion damage to those who did. Radical formation in these two groups were 0.35 and 9.0 mumol x 100 g-1, respectively (p < 0.0005). PMID- 8482303 TI - Impact of ischemia on tissue oxygenation and wound healing: intravital microscopic studies on the hairless mouse ear model. AB - To determine the effect of ischemia on tissue oxygenation and the healing of experimental wounds, chronic ischemia was induced in the ears of hairless mice by ligating 2 of the 3 main nutritional arteries. Tissue ischemia was verified by measurement of transcutaneous pO2 (tcpO2) prior to and on days 3, 6, 9, 12 and 15 after vessel ligation. TcpO2 values decreased from 24 to 6 mm Hg at day 2 after ligation, and slowly recovered to 12 mm Hg at day 12 after vessel ligation. In animals treated with the vasoactive drug buflomedil (3 mg/kg BW i.v., startling 2 days after vessel ligation) tcpO2 values were significantly higher on days 6 and 9 when compared to saline-treated control animals. In order to find out whether the enhanced tissue oxygenation resulted in enhancement of healing of wounds, we created circular wounds (diameter = 2.5 mm, depth 0.1 mm) on ischemic ears 2 days after vessel ligation. The wound surface area was measured by means of intravital fluorescence microscopy and digital planimetry at 3-day intervals until the time of wound closure. These experiments were performed on buflomedil-treated and control animals receiving equivalent amounts of saline. The reduction of wound surface area was accelerated and wound closure time was reduced from 15 days in control animals to 12 days in buflomedil-treated animals (p < 0.01). Functional capillary density as well as the microhemodynamic parameters microvessel diameter and red blood cell velocity were not different between buflomedil-treated and control animals. PMID- 8482304 TI - Bursting strength of experimental colonic anastomoses. A methodological study. AB - This study was performed to evaluate the validity of the bursting strength test of experimental anastomoses. By a combination of measuring the intraluminal physiological pressure during the test procedure with a radiological detection of the anastomosed intestinal segment until disruption it was demonstrated that the bursting pressure is a meaningful parameter since the maximum pressure equals the time of anastomotic leak. At day 6 60% of the tested segments disrupted outside the anastomotic line. This indicates that the bursting strength test is not a valid measure for determining the strength of colonic anastomoses after the 4th to 5th postoperative day. Moreover, the bursting wall tension parameter was evaluated. Assessment of the anastomotic radius demonstrated significant differences when the anastomotic radius at disruption was determined from the amount of inflated contrast compared with the radius detected radiologically. These differences had the effect that the wall tension at burst compared with the wall tension determined from direct radius measurement on day 4 was 61% higher than the wall tension determined from the amount of inflated contrast with no correction for elongation of the tested segment, and 36% higher than the wall tension determined from the amount of inflated contrast and corrected for elongation of the segment. No differences in the bursting strength were found between inflation rates of 2.5 and 5.0 ml.min-1. In conclusion, the bursting strength test is a meaningful parameter since the maximum physiological pressure equals the time of anastomotic radiological disruption, and the bursting pressure is a more exact parameter for measuring the bursting strength than the bursting wall tension. PMID- 8482305 TI - Myoelectric activity of an ileal isoperistaltic or antiperistaltic loop interposed between colon and rectum: an experimental study in pigs. AB - The myoelectric activity of 25-30 cm ileal loops interposed isoperistaltically or antiperistaltically between colon and rectum was investigated 1-3 and 20-22 weeks after surgery, in growing pigs chronically fitted with intraparietal electrodes on the loop and the ileum. The fundamental motor profile of the small intestine consisting of migrating myoelectric complexes (MMC) was present on both loops; the MMCs were propagated on the antiperistaltic loop in the original anatomical direction. There was no coordination between the occurrence of phase 3 on the loop and the ileum. Some minor differences concerning the duration, the frequency and the velocity of propagation of phase 3 were observed between the loops and the ileum. Moreover propagated clusters of spike bursts and propagated long duration spike bursts appeared on the isoperistaltic and antiperistaltic loop, respectively, but not on the ileum. No prominent differences in the motor profiles of the loops have been observed between 1-3 and 20-22 weeks after surgery. It is concluded that despite the presence of semisolid contents with an abundant microflora the fundamental intestinal motor profile persists in ileal loops interposed between colon and rectum. PMID- 8482306 TI - Intracerebroventricular infusion of neurotensin suppresses gastric acid secretion in dogs. AB - Synthetic neurotensin (NT) was infused intracerebroventricularly in 14 mongrel dogs to study the effects of the peptide on gastric secretion and on gastrin and NT levels. The infusion was performed with a specific apparatus, and gastric fluid was collected with a Pavlov pouch. NT was given in two series of experiments: as a bolus intracerebroventricular injection of 269.8 pmol/kg and as a continuous intracerebroventricular infusion at a rate of 539.6 pmol/kg/h for 30 min. The bolus injection caused a very significant decrease of gastric fluid volume, a significant decrease of HCl output and a significant increase of its pH, while serum immunoreactive gastrin increased significantly. The continuous infusion of NT caused similar changes in gastric secretion. The plasma NT levels did not change. In conclusion, the intracerebroventricular administration of NT increases the serum gastrin levels, decreases the volume and HCl content of gastric fluid, and increases its pH. PMID- 8482307 TI - Comparative study of augmentin versus metronidazole/gentamicin in the prevention of infections after appendicectomy. AB - Augmentin as single agent was compared to the combination of metronidazole/gentamicin in the prevention of sepsis after appendicectomy. Two hundred patients admitted to Riyadh Central Hospital with a clinical diagnosis of acute appendicitis were enrolled in a prospective randomized study. All patients had a preoperative chest X ray, CBC, urinalysis and any other necessary investigations. Patients received either drug regime intravenously, 30 min prior to surgery. The overall incidence of wound infections in the Augmentin group was 8% as compared to 14% in the metronidazole/gentamicin group. There were no intra abdominal abscesses in either group. Patients with perforated or gangrenous appendices received a 3- to 5-day course of treatment. All the early wound infection (2-4 days after operation) occurred in patients with gangrenous or perforated appendices. The results were studied statistically using chi 2 and there was no statistically significant difference between the infection rates in the two treatment groups whatever the state of the appendix at operation. Augmentin is as effective and well-tolerated as metronidazole/gentamicin in the prevention of wound infection following appendicectomy. The ease of administration of one drug with added anti-anaerobic property makes Augmentin superior to the tested combination. PMID- 8482308 TI - Comparison of two methods of autologous intrasplenic hepatocellular transplantation in partially hepatectomized dogs. AB - Autologous hepatocellular transplantation using reflux into the spleen via the venous tributaries was compared in 65% hepatectomized dogs to direct injection into the splenic pulp. Transplantation into the spleen via the inferior terminal polar splenic vein led to a better survival rate (50 vs. 0%). Hepatocytes embolization to the intrahepatic portal vein system was observed. Although hepatocyte transplantation into the spleen can be accomplished either by direct punction of the spleen or by retrograde injection into a splenic vein, the second method decreases the frequency of cell embolization. PMID- 8482309 TI - Surgical technique for cardiomyoplasty and iterative transthoracic biopsies in an experimental goat model. AB - Cardiomyoplasty is a new surgical procedure using transformed skeletal muscle to reinforce or substitute for the myocardium. For the purpose of studying surgical technique and investigating basic questions, we have developed a model of reinforcement cardiomyoplasty. Herein, we describe anesthetic management, surgical technique, and the technique for iterative transthoracic biopsies. This model has proven to be valuable in several long-term studies involving more than 30 goats. Preliminary data to ascertain the efficacy of the proposed technique are provided. PMID- 8482310 TI - Valvular colonic sphincter substitutes. An experimental study in dogs. AB - Three types of colonic sphincter substitutes were placed at an abdominal colostomy in dogs. Simple valve construction (8) was based on orthograde intussusception of the colon over 3.5 cm. In calibrated valves (6) the intraluminal pressure was increased by reducing the diameter of the overlying muscle coat. Reverse smooth muscle plasties (5) and simple colostomies (5) served as controls. Immediately after construction highest pressure (50 +/- 8.9 mm Hg) was obtained in calibrated valves. After 1 month the pressure dropped to 20 mm Hg, but remained stable thereafter. Although valvular constructions cannot maintain high pressure, they may be useful as substitutes for the internal anal sphincter by filling up the lumen so that the action of a surrounding striated muscle ring becomes more effective. PMID- 8482311 TI - Effects of PGE1 in experimental vasoconstrictive pulmonary hypertension. AB - The pulmonary vascular and systemic effects of PGE1 were studied in a canine model of pulmonary hypertension. Systemic arterial, central venous and pulmonary arterial pressures were monitored and an electromagnetic flow probe was placed around the ascending aorta for continuous cardiac index (CI) measurements. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and inferior vena cava. Gradual opening of this fistula significantly affected CI and these values were used to generate pressure-flow curves (pulmonary arterial pressure (PAP)/CI). Following PGF2 alpha infusion (5-10 micrograms/kg/min) significant pulmonary hypertension was observed (2- to 3-fold increase in PAP). PGF2 alpha infusion also resulted in a significant rise in heart rate and systemic vascular resistance (SVR) while CI was reduced. PGF2 alpha significantly increased both the line slope (vascular resistance) and intercept (outflow pressure) of the pressure-flow curves. Intravenous PGE1 infusion in doses ranging from 40 to 320 ng/ml/min elicited a dose-dependent reduction of both pulmonary and systemic vascular resistances, the former being slightly more affected. With PGE1 infusions only the intercept of the pressure flow curve was affected suggesting that specific components of the pulmonary vascular bed modulating the outflow pressure were involved. High doses of PGE1 significantly decreased arterial PO2, indicating that this prostaglandin derivative deteriorates pulmonary gas exchanges. PMID- 8482312 TI - Immunorestorative effect of thymostimulin on surgery immunodepression: experimental model. AB - The purpose of the present study is to ascertain the immunorestorative effect of two different drugs on immunodepression induced by small bowel surgical resection in an experimental model. The potential immunorestorative effect has been measured by the ability of the drug to avoid the delay of skin allograft rejection induced by surgery and the inhibition of CD4/CD8 index changes induced by surgery in spleen tissue. 120 Wistar-Furth rats (age 12-16 weeks) anesthetized with a single intramuscular dose of ketamine (25 mg), diazepine (4 mg) and atropine (0.1 mg) were allotted to two main groups. One group received a skin graft (SG) from Fisher 344 rats and was treated with placebo, Inmunoferon (AM-3 polypeptidic drug) or TP-1 (thymostimulin) before the experiment (groups I, II, III) or treated with placebo, Inmunoferon or TP-1 before the experiment and underwent enterectomy and anastomosis (groups IV, V, VI). On the 2nd, 5th and 8th postoperative days, biopsies of the SG were taken and the signs of rejection were microscopically studied and evaluated by a pathologist as zero, incipient, moderate or massive. The other group was treated similarly, but the animals did not receive a SG and were splenectomized 5 days later. CD4 and CD8 lymphocyte subpopulations were identified by means of immunoperoxidase technique and monoclonal antibodies. Thymostimulin is able to stimulate the presence of SG rejection signs on the 2nd postoperative day in nonenterectomized animals and on the 8th postoperative day in nonenterectomized animals and on the 8th postoperative day in enterectomized rats and is able to avoid the decrease of the CD4/CD8 index in spleen tissue after surgical immunodepression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482313 TI - In vitro studies on PMN-independent endothelial cell damage in trauma: decrease of PMN-endothelial cell adherence by fibrinogen degradation products and disturbance of endothelial cell membrane integrity by trauma serum. AB - Trauma favors the development of adult respiratory distress syndrome (ARDS). Adherence of polymorphonuclear leukocytes (PMN) to endothelial cells (EC) with subsequent EC damage by the respiratory burst products and proteases of the PMN is thought to be one of the basic mechanisms in the pathogenesis of ARDS. Recent studies have shown that there might also be PMN-independent mechanisms of EC damage. It would speak for PMN-independent EC damage if in the state of risk for this damage factors were found which decrease PMN activity or if EC damage appeared without PMN. Because in trauma and sepsis pathologic coagulation with high levels of fibrinogen degradation products (FDP) is often diagnosed, we investigated whether FDP-D and FDP-E might influence PMN adherence to EC. We also investigated whether serum of traumatized patients might provoke EC damage in a PMN-independent system in vitro. To achieve this we evaluated the viability of EC using a fluorescence staining method. We found that both FDP-D and FDP-E decreased PMN adherence to human EC significantly (p < 0.01) at a concentration of 50 micrograms/ml. Furthermore we found that EC membrane integrity can be disturbed by serum of trauma patients. These results suggest that in trauma also PMN-independent mechanisms are important for EC damage. PMID- 8482314 TI - The effect of portal hypertension on gastric epithelial proliferation in rats. AB - We investigated the effect of portal hypertension over time on gastric epithelial proliferation in rats. Portal-vein ligation (PVL) was applied to fourteen Wistar rats to produce experimental portal hypertension: seven rats (PVL2) had histological analysis after 2 months and the remaining seven (PVL4) after 4. An additional group of seven was employed as a control. Each rat was injected with bromodeoxyuridine and killed an hour later to assess gastric epithelial proliferation by an immunohistochemical staining technique. The labeling index between PVL and control animals differed significantly (p < 0.05). Labeling indices in fundic mucosa were 5.7 +/- 0.2% in controls, 3.9 +/- 0.3% in PVL2 rats and 4.0 +/- 0.3% in PVL4 rats, while in antral mucosa the corresponding figures were 7.5 +/- 0.6, 4.6 +/- 0.3 and 4.0 +/- 0.3%. In neither fundic nor antral mucosa was the total mucosal thickness significantly different between the control and PVL rats. In the PVL2 group, the frequency distribution of labeled cells showed a shift toward the mucosal surface in fundic glands. No significant differences between the two PVL groups were observed in any of the studied parameters. This study suggests that portal hypertension may inhibit gastric epithelial proliferation in rats. PMID- 8482315 TI - 27th annual scientific meeting of the European Society for Clinical Investigation, April 14-17, 1993, Heidelberg, Federal Republic of Germany. Abstracts. PMID- 8482316 TI - The effect of flunarizine on central nervous system oxygen toxicity in rats. AB - The toxicity of hyperbaric oxygen in the central nervous system is expressed by generalized tonic-clonic seizures. In the search for drugs effective against these seizures, we tested flunarizine, a calcium antagonist known to have antiepileptic properties and only minimal cardiovascular side effects. 49 rats with chronic cortical electrodes were injected i.p. with six different doses of flunarizine (10-300 mg/kg) or vehicle, before exposure to 0.5 MPa oxygen. Two doses of flunarizine and vehicle were given to rats exposed to oxygen with 5% CO2 at an absolute pressure of 0.5 MPa. EEG and spectral analysis of background EEG activity were monitored. The duration of the latent period before the appearance of electrical discharges in the EEG was used as an index of oxygen toxicity. There was no statistical difference between the duration of the latent periods for the seven groups treated by flunarizine or by vehicle on exposure to 0.5 MPa pure oxygen (P = 0.9 in ANOVA), but on exposure to oxygen with CO2, there was significant prolongation of the latent periods in comparison with vehicle (P < 0.001). Our results suggest that on exposure to hyperbaric oxygen, the antiepileptic effect of flunarizine might be masked, probably by its cerebral antivasoconstrictive effect. PMID- 8482317 TI - An evaluation of the biological significance of aluminium in plasma and hair of patients on long-term hemodialysis. AB - In hemodialyzed patients, the risk of toxicity attributed to the body accumulation of aluminium (Al) justifies the need for monitoring Al in various human media. In this study, Al concentrations in the hair and plasma of 78 hemodialyzed patients with chronic renal failure and of 351 healthy volunteers were measured by electrothermal atomic absorption spectrometry with Zeeman effect. Plasma Al concentrations in patients were significantly higher than in the controls and positively correlated with time on dialysis. Hair Al levels were widely distributed with no significant distinction between patients and controls. On the subject of establishing correlation, the authors stress the importance of taking into account the kinetics of the elimination of minerals from hair. Even when this was done, in the patient group there was no statistical link between plasma and hair Al levels. Hair Al analysis is of no value as an indicator of body Al accumulation. PMID- 8482318 TI - Long term effects of amlodipine on organ damage, stroke and life span in stroke prone spontaneously hypertensive rats. AB - The long term effects of amlodipine, a new long acting Ca2+ channel antagonist on organ damage, stroke and life span, were examined in stroke prone spontaneously hypertensive rats (SHRSPs). Blood pressure of the SHRSPs increased over the first 16 weeks and reached a stable level of about 250 mmHg in controls and about 200 mmHg in the amlodipine treated group. At 15 weeks after starting amlodipine treatment, all control SHRSPs exhibited varying degrees of myocardial fibrosis, proliferative and/or necrotic vasculitis and glomerular lesions, whereas only a few animals in the amlodipine group showed slight lesions. The average life span of animals was estimated to be 43.3 weeks and 71.1 weeks for control and amlodipine groups, respectively, which suggested a 1.6-fold prolongation of their life span by amlodipine treatment. These results indicate that the long term treatment of amlodipine suppresses the incidence of organ damage and stroke in SHRSPs and prolongs their life span. PMID- 8482319 TI - The metabolism and activation of 15,16-dihydrocyclopenta[a]phenanthren-17-one by cytochrome P-450 proteins. AB - The in vitro metabolism and activation to mutagens of 15,16 dihydrocyclopenta[a]phenanthren-17-one (CPP-17-one) were investigated using hepatic preparations from rats pretreated with prototype inducers of the cytochrome P-450-dependent mixed-function oxidases. Aroclor 1254-induced microsomes were the most effective metabolisers of this compound, the major metabolites being oxidation products of the bay region A ring. To a lesser extent hydroxylation of the non-aromatic D ring occurred, the products being the 15- and 16-hydroxyderivatives. Oxidation of the A ring was also achieved with microsomes from benzo[a]pyrene-treated rats but not with those from rats treated with clofibrate, phenobarbitone, isoniazid, dexamethasone and CPP-17-one itself, where the metabolites were primarily the oxidation products of the D ring. When CPP-17 one was used as a promutagen in the Ames test, only microsomes from Aroclor 1254 treated rats could elicit a positive mutagenic response. When 3,4 dihydrodihydroxy-CPP-17-one, the precursor of the ultimate mutagen, was used as the promutagen, a positive response was observed with microsomes from Aroclor 1254- and benzo[a]pyrene-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482320 TI - Toxicity of paracetamol in cultured chick hepatocytes treated with methotrexate. AB - Cultured chick hepatocytes were used to investigate the hepatotoxicity of methotrexate alone and in combination with paracetamol. Treatment with methotrexate alone at concentrations as high as 1 mg/ml resulted in no toxicity in cultured chick hepatocytes, as indicated by no detachment of cells and no effect on protein synthesis or on release of the intracellular enzyme lactate dehydrogenase. However, treatment with methotrexate alone resulted in a 30% decrease in reduced glutathione levels. Combined treatment with methotrexate and paracetamol was toxic, but only in cells preinduced for cytochrome P450 1A by treatment with beta-naphthoflavone. Under these conditions, methotrexate lowered the threshold concentration of paracetamol at which toxicity was observed. This methotrexate-mediated increase in paracetamol toxicity was associated with decreased formation of the glucuronide, sulfate and thiol metabolites of paracetamol and with increased covalent binding of radiolabeled paracetamol to macromolecules. In cells pretreated with beta-naphthoflavone, additional treatment with either methotrexate or buthionine sulfoximine, an inhibitor of glutathione synthesis, together with paracetamol, was associated with decreased restoration of glutathione levels. These results suggest that methotrexate increased paracetamol toxicity by decreasing the amount of glutathione available for conjugation with reactive metabolites of paracetamol. PMID- 8482321 TI - Cytogenetic effects of promutagens in genetically engineered V79 Chinese hamster cells expressing cytochromes P450. AB - V79 Chinese hamster cell lines genetically engineered to express rat CYP2B1, CYP1A1, CYP1A2, and their parental cell lines V79-MZ, without acetyltransferase, and V79-NH, with acetyltransferase, were studied for chromosome aberrations and sister chromatid exchange induced by aflatoxin B1, cyclophosphamide, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine. The parental V79 cell lines did not show clastogenic effects. Significant clastogenic effects were observed after an 18 h exposure to aflatoxin B1 and cyclophosphamide in CYP2B1 expressing cells, to benzo[a]pyrene in CYP1A1 and CYP1A2 expressing cells, to 7,12-dimethylbenz[a]anthracene and dimethylnitrosamine in cells, expressing CYP1A2 with or without acetyltransferase, and to cyclophosphamide in cells expressing both CYP1A2 and acetyltransferase. A significant sister chromatid exchange inducing effect was found after a 24 h exposure in each of the genetically engineered cell lines, except for benzo[a]pyrene and 7,12 dimethylbenz[a]anthracene in CYP2B1 expressing cells, and for benzo[a]pyrene in cells expressing both CYP1A2 and acetyltransferase. Thus, a battery of cell lines genetically engineered for metabolic competence may serve as a tool for investigating chromosomal changes induced by activated xenobiotics. PMID- 8482322 TI - Nicotine and its major metabolite cotinine have different effects on aldosterone and prolactin serum levels in the normal male rat. AB - Nicotine (0.01-1.0 mg/kg, i.p.) or cotinine (0.003-1.0 mg/kg, i.p.) treatment was administered to Sprague-Dawley male rats. The time-effect curves (5, 10, 30, 60 and 180 min) were analyzed. Nicotine dose-dependently increased blood aldosterone and corticosterone levels with a peak effect 10 min after the intraperitoneal injection. Nicotine treatment weakly decreased serum levels of aldosterone at 2 h, possibly as a consequence of nicotine metabolising to cotinine, resulting in higher serum levels of cotinine than nicotine. Cotinine dose-dependently reduced serum aldosterone levels, an effect which became more marked with time, leaving plasma corticosterone unchanged. Nicotine dose-dependently increased serum prolactin levels at 5 and 10 min following treatment, an effect which had diminished at 30 min. Cotinine dose-dependently reduced serum prolactin levels at 5 min followed by a dose-dependent increase at 10 min after which a dose dependent reduction was again found after 30 min post treatment. In conclusion, acute nicotine and cotinine treatment produced opposite effects on aldosterone and prolactin serum levels. The prolonged effect of cotinine on aldosterone levels may be involved in changes in brain function, and may be connected to the development of withdrawal effects after stopping cigarette smoking. As reported by other investigators, nicotine produced enhanced plasma corticosterone levels while cotinine treatment was ineffective. Since cotinine induced marked changes in serum prolactin levels while leaving LH levels unchanged, it seems plausible that cotinine affects neuroendocrine regulation via mechanisms not primarily related to circulatory effects. Thus, an action at the median eminence--pituitary level seems likely. PMID- 8482323 TI - Endothelium-dependent relaxation in rabbit aorta after cold storage. AB - The extent of preservation of endothelial, smooth muscle and neurogenic function following cold storage was studied in rabbit thoracic aorta. Relaxation responses to acetylcholine and sodium nitroprusside were compared between fresh aortic rings and rings that had been stored in a refrigerator for 2-8 days at 4 degrees C. In fresh aortic rings, the addition of acetylcholine to precontracted vessels resulted in dose-dependent relaxation. The magnitude of relaxation was gradually decreased after 4-8 days of cold storage. Relaxation in response to sodium nitroprusside did not change. Following cold storage contractions of aortic rings in response to noradrenaline and phenylephrine were not reduced. Contractile responses induced by transmural nerve stimulation were gradually attenuated with the length of cold storage. Electron microscopy after 4 days showed partial damage of endothelial cells (slightly vacuolized mitochondria). After 8 days, endothelial cells were destroyed; only membranous material was present. The structure of smooth muscle cells was only partially changed even after 8 days. Sympathetic nerve endings on the 4th day were partially, but on the 8th day completely destroyed. These results suggest that after cold storage of rabbit aorta, the gradual reduction of endothelium-dependent relaxation is probably caused by a decrease in production of the endothelium-derived relaxing factor due to the destruction of endothelial cells. PMID- 8482324 TI - Comparison of cardiac actions of doxorubicin, pirarubicin and aclarubicin in isolated guinea-pig heart. AB - The cardiac actions of doxorubicin were compared with those of pirarubicin and aclarubicin to understand the mechanisms responsible for differences in cardiotoxic effects of anthracycline agents. In left atrial muscle preparations obtained from guinea-pig heart and stimulated at 2 Hz, anthracyclines produced positive inotropic effects. The magnitude of the effect was pirarubicin > doxorubicin > aclarubicin. The order for depression of potentiated postrest contraction and prolongation of the time to peak twitch tension was doxorubicin > pirarubicin > aclarubicin. Drug washout following a 2-h incubation with 100 microM doxorubicin prevented a further increase in the time to peak twitch tension, caused a marked recovery of depressed potentiated postrest contractions, and augmented the positive inotropic effect. Pirarubicin and doxorubicin, but not aclarubicin, caused a parallel rightward shift of the dose-response curve for the negative inotropic effect of acetylcholine. The potency of inhibition of [3H]quinuclidinyl benzilate binding was pirarubicin > doxorubicin > aclarubicin. These results indicate that three anthracycline anticancer agents share similar effects on cardiac muscle contractility and on muscarinic acetylcholine receptors. The actions of aclarubicin were weak compared to those of doxorubicin or pirarubicin. Increases in the time to peak twitch tension and the depression of potentiated postrest contraction are apparently mediated by mechanisms different from those responsible for the positive inotropic effects or antagonism at muscarinic acetylcholine receptors. PMID- 8482325 TI - Hypotensive action of 5-HT receptor agonists in the vitamin B6-deficient hypertensive rat. AB - Feeding a vitamin B6-deficient diet to rats causes a moderate hypertension. The blood pressure responses to 5-HT1A receptor agonists were studied in conscious vitamin B6-deficient hypertensive rats. They were all effective in lowering blood pressure with the following rank order of potency: 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT) > flesinoxan > 5-methylurapidil > urapidil. The putative 5-HT1A receptor antagonist spiroxatrine by itself, did not have any effect on the blood pressure at the doses used (0.01-1 mumol/kg). However, dose dependently, it antagonized the hypotensive effect of flesinoxan and urapidil. The alpha 1-adrenoreceptor antagonist prazosin, on prior treatment, did not change the hypotensive effect of either flesinoxan or urapidil. The alpha 2 adrenoreceptor agonist clonidine dose dependently (0.01-0.1 mumol/kg) reduced blood pressure. This effect of clonidine was unaffected by spiroxatrine, but was dose dependently antagonized by the alpha 2-adrenoreceptor antagonist yohimbine. Binding studies with [3H]8-OH-DPAT indicated that the affinity and Bmax of 5-HT1A receptors was increased in vitamin B6-deficient hypertensive rats. The results suggest that decreased synthesis of 5-HT in brain regions and the consequent alterations in 5-HT receptors in the vitamin B6-deficient rats may be the underlying cause of the hypertension seen in these animals. PMID- 8482326 TI - Effect of chronic treatment with TFMPP, a 5-HT1 receptor agonist, on food intake, weight gain, plasma insulin and neuropeptide mRNA expression in obese Zucker rats. AB - 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP), a 5-HT1 receptor agonist, decreases food intake in rats when given acutely. The present investigation was performed to study the chronic effects of TFMPP on food intake and weight gain in genetically obese Zucker rats. Neurochemical and endocrine data on possible mechanisms involved in the action of TFMPP were collected at the end of the study. TFMPP (4 mg/kg per day s.c.) significantly reduced food intake on the 1st and 7th days, but no longer on the 14th and 28th days. Reduced food intake was associated with decreased body weight gains during the first two weeks of treatment, but no effect was found thereafter. Plasma insulin concentration was significantly lowered by TFMPP treatment without impairment of glucose homeostasis. In situ hybridization analysis did not reveal changes in the expression of preprocorticotropin-releasing factor mRNA in the paraventricular nucleus or preproneuropeptide Y mRNA in the arcuate nucleus. Chronic TFMPP administration significantly reduced the density of 5-HT2 receptors, as measured by quantitative receptor autoradiography, in the claustrum and cerebral cortex, but not 5-HT1C receptor density in the choroid plexus. It is concluded that the anorectic and weight gain-lowering effects of TFMPP decrease during long-term treatment in obese Zucker rats. PMID- 8482327 TI - Pharmacological characterization and autoradiographic localization of dopamine D1 receptors in the human umbilical artery. AB - Combined in vitro radioreceptor binding and autoradiographic techniques with [3H]SCH 23390 as a ligand were used to analyze the pharmacological profile and anatomical localization of dopamine D1 receptor sites in sections of human umbilical artery. The ligand was bound to sections of the artery in a manner consistent with the labelling of D1 receptors. These receptors, which show a fetal-to-maternal gradient with the highest concentration near the placenta, are located within the smooth muscle layer of the umbilical artery. The above findings suggest that endogenous dopamine may be involved in the control of the tone of the umbilical artery through the interaction with D1 receptors. PMID- 8482328 TI - Reduction of myocardial infarct size by ramiprilat is independent of angiotensin II synthesis inhibition. AB - The angiotensin-converting enzyme inhibitor ramiprilat, the angiotensin II receptor antagonist losartan, angiotensin II, ramiprilat plus angiotensin II, or saline (N = 6 each group), were administered i.v. in anesthetized, open-chest rabbit preparations of acute myocardial ischemia. Animals were instrumented for measurement of systemic hemodynamics and left ventricular +dP/dtmax, then subjected to 30 min of left anterior descending coronary artery occlusion (marginal branch) followed by 2 h of reperfusion. Ramiprilat (50 micrograms/kg), losartan (10 mg/kg), or saline were administered prior to reperfusion, and angiotensin II (2.5 ng/kg per min) was infused 15 min prior to occlusion and throughout the remainder of the experiment. Losartan was supplemented (10 mg/kg) after 1 h of reperfusion. These non-hypotensive doses of ramiprilat and losartan were demonstrated to significantly antagonize the systemic pressor effects of i.v. challenge with angiotensin I (15% of control, maximum) and II (5% of control, maximum), respectively, for the duration of the experiment. Systemic hemodynamic and +dP/dtmax changes due to occlusion/reperfusion or drug administration were similar between treatment groups. Infarct size was measured post-experimentally using tetrazolium staining and is reported as a percent of area at risk. Infarct size/area at risk (%) was significantly lower in rabbits administered ramiprilat only (20 +/- 6%*) or ramiprilat plus angiotensin II (26 +/- 5%*), compared to those receiving saline (41 +/- 6%), angiotensin II (51 +/- 4%), or losartan (52 +/- 4%, mean +/- S.E.M., * P < 0.05). These data indicate that direct angiotensin II receptor stimulation or receptor antagonism does not alter the degree of myocardial necrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482329 TI - Anti-leukotriene effects of WY-50,295 tromethamine in isolated guinea pig pulmonary tissues. AB - The abilities of WY-50,295 tromethamine, a 5-lipoxygenase inhibitor, to inhibit antigen-induced leukotriene (LT) release from guinea pig lung fragments, and to prevent LTD4 or antigen-induced contraction of isolated guinea pig tracheal muscle were compared with the activities of zileuton and MK-886 (two selective 5 lipoxygenase inhibitors), and LY171883 (a LTD4 receptor antagonist). In fragmented guinea pig lung, WY-50,295 tromethamine inhibited antigen-induced LT release with an IC50 of 0.63 microM, and was 4.6- and 5.2-fold more potent than zileuton and MK-886, respectively. WY-50,295 tromethamine differed from these 5 lipoxygenase inhibitors, however, in that WY-50,295 tromethamine competitively antagonized LTD4-induced tracheal contractions (pA2 = 6.06) at concentrations that inhibited LT release. LY171883 was an effective LTD4 receptor antagonist (pA2 = 6.96), that only inhibited antigen-induced LT release at higher concentrations (IC50 = 7.9 microM). WY-50,295 tromethamine almost completely inhibited antigen-induced leukotriene-dependent tracheal contractions, whereas high concentrations of zileuton, MK-886, or LY171883 produced only partial inhibition. This partial inhibition was likely to result from 'breakthrough' 5 lipoxygenase activity, because combinations of zileuton plus MK-886 or zileuton plus LY171883, were more effective than zileuton, MK-886, or LY171883 alone. The greater efficacy of WY-50,295 tromethamine in the antigen-challenged guinea pig trachea is likely to result from its combined abilities to prevent LT biosynthesis and block LTD4 receptors. PMID- 8482330 TI - Selective and complete blockade of acetylcholine-induced relaxation in rabbit aortic rings by N omega-nitro-L-arginine but not by glybenclamide. AB - This study addressed the possibility that acetylcholine-induced relaxation in the rabbit aorta is mediated by dual mechanisms: one N omega-nitro-L-arginine (NLA) sensitive, the other glybenclamide-sensitive. Acetylcholine, nitroglycerin and BRL38227 (lemakalim), an activator of glybenclamide-sensitive potassium channels, were added to an organ bath containing rabbit aortic rings in a cumulative manner in the absence or presence of NLA and/or glybenclamide. NLA inhibited acetylcholine-induced relaxation and potentiated the relaxant response to nitroglycerin. BRL38227 caused a dose-dependent relaxation in rabbit aortic rings, and 30 microM glybenclamide produced essentially complete inhibition of this relaxation. Glybenclamide alone produced no inhibition of acetylcholine induced relaxation. These results indicate that glybenclamide-sensitive potassium channels in the rabbit aorta play no role in mediating the relaxant response to acetylcholine, while NLA can produce a selective and essentially complete blockade of the relaxant response to acetylcholine in the rabbit aorta. PMID- 8482331 TI - Flow injection fluorescence microscopy: a novel tool for the study of cells through controlled perfusion. AB - Current methods of microscope stage perfusion do not take full advantage of existing technology for precise fluid control. The concept of flow injection, used extensively by analytical chemists, is described and its application to the fluorescence microscopic study of cultured cells is proposed. Using this technique, cells may be exposed to single or multiple reagent zones of almost any profile, sequence, and duration, with computer-controlled precision. A flow injection system is employed in conjunction with a novel perfusion chamber--the fountain cell. The ability of the flow injection system to perfuse cells with a reagent with a reproducibility of 1% RSD is demonstrated. The system was used to monitor changes in calcium levels in baby hamster kidney cells loaded with FURA-2 as a result of stimulation with a precisely timed concentration of ionomycin. The unique feature of the technique is that it allows a series of responses of a given cell to be directly compared to each other. PMID- 8482332 TI - The basement membrane protein BM-600/nicein codistributes with kalinin and the integrin alpha 6 beta 4 in human cultured keratinocytes. AB - The observation is reported that in low-passage human keratinocyte colonies cultured under conditions that allow full epidermal differentiation (i) the basement membrane protein BM-600/nicein, identified by the mAb GB3, is codistributed with laminin and collagen type IV as well as with the bullous pemphigoid antigen in footprints deposited by growing and migrating colonies; (ii) the integrin heterodimer alpha 6 beta 4 is codistributed with the same molecules suggesting its spatial association with basement membrane components; (iii) the distribution pattern of alpha 6 beta 4 and BM-600/nicein underneath individual cells is identical and is characterized by a typical "leopard skin" pattern complementary to the distribution of submembraneous F-actin microfilament network; (iv) a rabbit polyclonal antiserum to kalinin (R4012) used in double label immunofluorescence staining with mAb GB3 shows that this protein has the same distribution as BM-600/nicein and this suggests that they are identically located; and (v) immunoprecipitation with mAb GB3 to BM-600/nicein and BM165 to kalinin shows identical bands suggesting that nicein and kalinin represent the same molecular entity. We suggest that alpha 6 beta 4 displays not only an adhesive role for keratinocytes in view of its reported association to hemidesmosomes but may also be involved in organizing the molecules of the epithelial extracellular matrix, including those forming the basement membrane zone and hemidesmosomes, a function proposed for other integrins in other cellular systems. PMID- 8482333 TI - Cytochalasin D-induced actin gene expression in murine erythroleukemia cells. AB - There is a dynamic equilibrium between monomeric G-actin and polymeric F-actin microfilaments (MFs) in eucaryotic cells. We have previously shown that disruption of MFs with cytochalasin D (CD) induced beta-actin gene transcription, resulting in elevated levels of beta-actin mRNA and protein synthesis. CD also inhibited cell growth by arresting progression through the S phase of the cell cycle. These CD-induced responses were reversible since recovering cells progressed through the G2 phase and resumed normal growth while beta-actin mRNA and protein synthesis rapidly returned to control levels. In the present study, we show that the response of beta- and gamma-actin genes is due to the synthesis of a protein(s) acting at a 5' regulatory element that may be independent of or require sequences in addition to the serum response element (SRE). CD induces beta- and gamma-actin mRNA in a dose-dependent manner, reaching a maximum of 20 fold over control mRNA levels at 30 microM. beta- and gamma-Actin gene expression was also induced 5-fold by serum stimulation of quiescent murine erythroleukemia (MEL) cells, while combined treatment with serum and CD had an additive effect. Two protein synthesis inhibitors, cycloheximide and puromycin, blocked the CD induced increase in beta-actin mRNA, in contrast to the serum-induced increase which is insensitive to inhibitors of protein synthesis. The rapid return of beta actin mRNA to basal levels following CD removal did not require protein synthesis nor did it require progression through the G2 phase of the cell cycle. A vector containing the 5' end of the beta-actin gene linked to a CAT reporter responded to CD when transfected into MEL cells, localizing the responsive element to the 5' portion of the beta-actin gene. By contrast, a minimal 99-bp actin promoter CAT construct containing a functional SRE did not respond to CD. PMID- 8482334 TI - Transformation of NIH/3T3 to anchorage independence by H-ras is accompanied by loss of suppressor activity. AB - Despite their familiar sensitivity to transformation by dominant-acting ras oncogenes, NIH/3T3 cells carry a ras suppressor. When tested by cell fusion they were able to suppress the anchorage-independent phenotype of both mouse and human cells transformed by activated H-ras or N-ras. This suppression occurred without a decrease in expression of the activated ras oncogene. Ras-transformed NIH/3T3 clones cured of their oncogene by benzamide treatment reverted to a nontransformed phenotype, but had lost the ability to suppress other ras transformants, indicating that their initial transformation was accompanied by suppressor loss. In hamster cells an active ras oncogene increased the rate of chromosome segregation by > 100-fold. These results suggest that in vitro transformation of NIH/3T3 cells by ras may be more similar to multistep in vivo tumor development than previously suspected, involving not only expression of an active oncogene but also loss of a suppressor activity, perhaps induced by the clastogenic oncogene. PMID- 8482335 TI - The regulation of GTP-binding proteins during fertilization and zygote differentiation in Dictyostelium discoideum. AB - The development changes in GTP-binding proteins and the regulation of their appearance by calcium ions were investigated during early sexual development in Dictyostelium discoideum. GTP gamma S strongly inhibited gamete cell fusion, while GDP beta S slightly augmented it, suggesting that G-proteins have a critical role in cell fusion. A 52-kDa protein recognized by an anti-GTP-binding site-specific immune serum, was abundant during calcium-dependent early sexual development but decreased in amount concomitant with cell fusion. This protein remained at high levels in Ca(2+)-deficient cultures, suggesting that its down regulation is linked to the events of sexual development. Analysis of substrates for cholera and pertussis toxin-mediated [32P]ADP-ribosylation in D. discoideum extracts determined that the 52-kDa protein is a G-alpha subunit similar to mammalian Gs. The 52-kDa protein was also detected in vegetative, asexual amoebae, but diminished rapidly within the first 2 h of starvation. Together these data indicate that the 52-kDa protein functions during the growth phase and is lost upon entry into either the sexual or asexual developmental programs. The amounts of several lower molecular weight GTP-binding proteins, ranging from 21- to 28 kDa, increased during the stage of zygote differentiation and their increases were calcium dependent. These data provide the first analysis of G proteins during sexual development of D. discoideum and lay the foundation for continued analysis of the signal transduction events mediating cell fusion and zygote differentiation. PMID- 8482336 TI - Secretion of endogenous 16-kDa beta-galactoside-binding lectin from vitamin A pretreated chick embryonic cultured skin. AB - Localization of endogenous beta-galactoside-binding 16-kDa lectin and its gene expression pattern were investigated during differentiation of chick embryonic skin in vivo and in vitro and were compared with those of a 14-kDa lectin. By light microscopy, immunostaining of the 16-kDa lectin was weak in the undifferentiated epidermis, while it became intense in the keratinized epidermis, particularly in the intermediate cells. Essentially the same staining pattern was observed both in vivo and in vitro. The gene expression pattern was consistent with these immunohistochemical observations. These results were similar to those of the 14-kDa lectin [1]. On the other hand, in the vitamin A-pretreated cultured skin, mucous metaplasia of the epidermis was induced and marked changes in localization of these two isolectins were observed. The 16-kDa lectin expression was increased in the epidermis, especially in the superficial cells, and the gene expression was detected in all layers of the epidermis. However, 14-kDa lectin expression was markedly reduced in the metaplastic epidermis. In the keratinized epidermis, detailed localization of these lectins under the electron microscope was almost the same. Both of them were located primarily along the plasma membrane, in the intercellular space, and in the desmosomes. In the mucous metaplastic epidermis, however, the localization of the 16-kDa lectin was completely different from that of the 14-kDa lectin; e.g., the former was detected in the mucous granules and on the microvilli of the superficial cells, while the latter was scarcely observed in the epidermis. The present results revealed that (1) the 16-kDa lectin as well as 14-kDa lectin were expressed during the epidermal differentiation and (2) much of the 16-kDa lectin was produced and secreted from the vitamin A-pretreated cultured epidermis, while 14 kDa lectin disappeared. In the view of these facts, it is suggested that (1) both 14- and 16-kDa lectins may play an important role in differentiation of the skin and (2) the gene expression of 14- and 16-kDa lectins is regulated independently. PMID- 8482337 TI - Effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on proliferation of young and senescent WI-38 human diploid fibroblasts. AB - The effects of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on the proliferation, protein kinase C activity (PKC), and c-fos gene expression were examined in cultures of young and senescent (90-95% lifespan completed) WI-38 human diploid fibroblasts. We observed that, following stimulation with medium containing 10% fetal bovine serum (FBS), the translocation of PKC from the cytosol to the particulate compartment was less efficient in senescent WI-38 cells than in young cells. However, when PMA was added to the medium, the intracellular distribution of PKC activity in old cells became nearly identical to that observed in young cells. The inducibility of c-fos mRNA by serum addition, which is a protein kinase C-dependent event, was significantly amplified in the presence of PMA. Moreover, the duration of peak c-fos expression, after stimulation by FBS and PMA, increased in senescent cells as compared to young cells. Our results reveal that the normal signal transduction pathway is altered in senescent, slowly proliferating human fibroblasts and that it can be partially restored in the presence of the tumor promoter PMA. PMID- 8482338 TI - Three pools of lysosomal enzymes in Tetrahymena thermophila. AB - Secretion of lysosomal enzymes into the extracellular surroundings has been observed in many eukaryotic cells. We studied the activity of lysosomal enzymes in different subcellular fractions of Tetrahymena thermophila to get more insight into this general phenomenon. By density gradient centrifugation a light and a dense fraction of lysosomal particles were found. Electron microscopy revealed that the light fraction mainly consists of cell surface membranes. By immunostaining a lysosomal enzyme (beta-hexosaminidase) was detected on the plasma membrane. The Triton X-114 assay showed that the light fraction as well as purified cilia (an enriched source of plasma membrane) contain lysosomal enzymes predominantly covalently bound to the membrane. The dense fraction contains both membrane-bound and soluble forms of lysosomal enzymes. By labeling phagosomes/phagolysosomes with magnetic particles the dense fraction can be subdivided into two lysosomal vesicle populations: phagolysosomes and a further population of lysosomal vesicles which can not be labeled. The relationship between membrane-bound and soluble enzyme forms in phagolysosomes and this unlabeled vesicle population is different: In phagolysosomes 80% of the acid phosphatase and 20% of the beta-hexosaminidase are membrane-bound, whereas in the unlabeled vesicles 42% of the acid phosphatase and 8% of the beta-hexosaminidase are bound to the membrane. Furthermore, we present results suggesting that the unlabeled vesicle population of the dense fraction is the source of secreted lysosomal enzymes. A working model summarizing our present knowledge about the connection of the three pools of lysosomal enzymes in Tetrahymena is presented. PMID- 8482339 TI - The large cytoplasmic domain is not required for concentration of N-CAM at cell cell contacts in transfected mouse neuroblastoma cells. AB - We examined the localization of the 140- and 180-kDa transmembrane isoforms of chicken N-CAM following transfection into mouse N2A neuroblastoma cells. Both isoforms were expressed at the cell surface and became partially or completely localized at areas of cell-cell contact after several days of culture or of in vitro differentiation. These results indicate that the presence of the large cytoplasmic domain of the 180-kDa N-CAM isoform is not necessary to bring about the localization of N-CAM to points of cell-cell contact. PMID- 8482340 TI - A sequential staining technique for karyotypic analysis of interspecific somatic cell hybrids. AB - We describe a sequential staining technique for the karyotypic analysis of interspecific mouse x human somatic cell hybrids. Fluorescence in situ hybridization of samples, previously stained using standard trypsin/Giemsa protocols, was instrumental in the identification of human chromosomes present in hybrid lines. This procedure not only provided a simple distinction between human and mouse chromosomes, but it also allowed the visualization and monitoring of human sequences present in interspecific translocations and subchromosomal fragments. PMID- 8482341 TI - Oleic acid blocks epidermal growth factor-activated early intracellular signals without altering the ensuing mitogenic response. AB - In EGFR-T17 cells, which express high levels of the epidermal growth factor (EGF) receptor, addition of a saturating dose of EGF (10 nM) leads to an increase in Ins(1,4,5)P3/diacylglycerol and also to cytosolic calcium [Ca2+]i due to both intracellular redistribution and influx from extracellular medium. Pretreatment of cells with cis-unsaturated nonesterified fatty acids such as oleic acid (1 to 100 microM) inhibited EGF-stimulated Ins(1,4,5)P3 generation and Ca2+ release from intracellular stores. Furthermore, such a treatment completely suppress Ca2+ influx in a dose-dependent manner. At doses capable of suppressing such early signals, oleic acid did not alter the process of EGF-mediated internalization of the EGF/EGF-receptor complex, suggesting that [Ca2+]i rise did not mediate receptor internalization. EGF-induced cell proliferation assessed by either thymidine incorporation into DNA, direct cell counting, and microscopic observation was not altered by oleic acid, at doses able to block EGF-mediated early signals. In conclusion, suppression of Ins(1,4,5)P3 generation and [Ca2+]i rises by oleic acid did not alter EGF-receptor internalization nor EGF-induced cell mitosis. Such results suggest that [Ca2+]i rise is not instrumental for EGF stimulated cell proliferation. PMID- 8482342 TI - Polysaccharides influence the aggregation of Dictyostelium discoideum cells and bind to developmentally regulated cell surface proteins. AB - Six of ten anionic polysaccharides studied were found to significantly reduce the adhesion of growth-phase Dictyostelium discoideum cells. However, only hyaluronic acid, chondroitin-4-sulfate and chondroitin-6-sulfate interfered with the adhesion of aggregation-competent cells. Neither EDTA-stable nor EDTA-sensitive adhesion of postaggregation cells were affected by the polyanions. The two chondroitin sulfates influenced the aggregation of cells in submerged cultures, long and broad aggregation streams being formed and the broad sheets of cells eventually building multilayered aggregates. Radioiodination of cell surface proteins followed by cellulose fiber affinity chromatography identified the same nine proteins bound by hyaluronic acid and the chondroitin sulfates, six of which were regulated during development. Protease-resistant anionic material isolated from cells bound the same surface proteins as the three glycosaminoglycans. Discoidin I bound to the uncoupled cellulose fibers, suggesting a structural role for the lectin in the extracellular slime sheath. Anionic polysaccharides and cell surface lectins that bind them may be involved in the cell recognition, cell aggregation, and the cell sorting that occurs during pattern formation. PMID- 8482343 TI - Studies on the cellular pathway involved in assembly of the embryonic sea urchin spicule. AB - Micromeres from the 16-cell stage sea urchin embryo were isolated and cultured in vitro in seawater containing 3% horse serum. Under these conditions these cells differentiate into spicule-forming, primary mesenchyme cells. To obtain insight into the route traveled by Ca2+ to form the pseudocrystalline spicule composed of CaCO3 and matrix proteins, studies with various inhibitors were undertaken. Experiments with members of several different classes of Ca2+ channel blockers established that the Ca2+ utilized for spiculogenesis must be taken up by the cells. Moreover, studies using two agents that disrupt the endomembrane system, monensin and brefeldin A, showed that both blocked spicule formation. Based on these experiments, we conclude that extracellular Ca2+ must enter the primary mesenchyme cells prior to being deposited extracellularly as CaCO3 and that this ion and/or the matrix proteins found in the spicule are routed through the secretory pathway that has been established to exist in a wide variety of other cell types. PMID- 8482344 TI - Phagocytosis by normal human melanocytes in vitro. AB - Phagocytosis is an important first step in processing of antigens ultimately to be presented in the context of MHC class II molecules on the cell surface. Degradation of internalized antigens can then proceed by fusion of the phagosome with organelles containing lysosomal enzymes. Evidence for the phagocytic capacity of cultured normal human skin melanocytes is provided, both by electron microscopy and by confocal laser scanning microscopy. The phagocytic capacity of melanocytes is approximately 5% of that found for cultured human dermal skin fibroblasts. However, in a mixed culture of keratinocytes and melanocytes, uptake of 1 micron latex beads in 72 h was found to be comparable for both epidermal cell types, implicating in vivo significance for phagocytosis by melanocytes. Furthermore, it is shown that phagosomes containing latex beads will fuse with melanosomes, indicating that melanosomes can function as specialized lysosomal organelles within normal human skin melanocytes. The present investigation indicates that melanocytes are equipped with the phagocytic machinery important for the processing of antigens and thus may function as accessory cells within the skin immune system. PMID- 8482345 TI - Enhanced expression of fibronectin during in vivo cellular aging of human vascular endothelial cells and skin fibroblasts. AB - Vascular endothelial cells are thought to play an important role in human aging as their senescence and/or detachment from vascular wall contribute to arteriosclerosis and high blood pressure in elderly persons. Since fibronectin is necessary for cell attachment and spreading and its increased expression has been reported in aging fibroblasts, we checked its expression in aortic endothelial cells aged in vivo. We found that the steady-state level of fibronectin expression increases with increasing donor age, while the labeling index of cultured cells decreases with age. The increased level of fibronectin expression correlated well with an increase in cell area. To explore whether these changes were a reflection of exhaustion of proliferation potential in vivo, we examined fibronectin expression in human umbilical vein endothelial cells aging in vitro. Very similar results were obtained, supporting the idea that vascular endothelial cells age in vivo by using up division potential. When we examined the expression of fibronectin in human skin fibroblasts aged in vivo and fetal lung fibroblasts aged in vitro, we obtained similar results. In conclusion, the level of expression of fibronectin and cell size increase during in vivo and in vitro aging of both endothelial cells and fibroblasts in a coordinate manner. PMID- 8482346 TI - Sphingosine blocks both membrane fusion and calmodulin-dependent phosphorylation of the 100-kDa protein of chick embryonic myoblasts. AB - Sphingosine, a potent inhibitor of protein kinase C, was found to block membrane fusion of chick embryonic myoblasts in culture. This effect was dose-dependent and could be reversed upon removal of the drug. Treatment with 12-O tetradecanoylphorbol 13-acetate, which is a powerful activator of protein kinase C and capable of preventing myoblast fusion, further potentiated the inhibitory effect of sphingosine. Thus, the sphingosine-mediated inhibition of myoblast fusion appears to be independent of protein kinase C. Sphingosine also decreased the phosphorylation state of the 100-kDa protein when given to the cell extracts, and this inhibition was competitive with calmodulin. Thus, sphingosine seems to act as a calmodulin antagonist. These results suggest that the sphingosine mediated inhibition of myoblast fusion may be associated with the inhibitory effect of the drug against the calmodulin-dependent phosphorylation of the 100 kDa protein. PMID- 8482347 TI - Cell cycle-dependent regulation of Ca2+ in young and senescent WI-38 cells. AB - During the in vitro senescence of the normal human diploid cell line WI-38, there is a loss of ability to initiate DNA synthesis in response to mitogens. This loss of replicative capacity is reflected in an increasing average length of G1 and a decreasing fraction of cells in the rapidly proliferating pool. Calcium ion (Ca2+) has been shown to be important for progression through the cell cycle and we have measured two processes which contribute to the regulation of intracellular Ca2+ in the early, mid, and late G1 phase of the cell cycle. Basal intracellular Ca2+ concentrations in quiescent cells as well as initial transient mobilization of Ca2+ stores following mitogenic stimulation by growth factors were equivalent in young and senescent cells. Calmodulin levels in young, quiescent cells decreased 50% in the first 4-6 h after stimulation with fresh serum and then increased two- to fourfold immediately prior to entry into DNA synthesis. Senescent cells did not exhibit this cell cycle-dependent pattern and calmodulin levels remained generally constant throughout G1, sometimes increasing slightly, prior to S phase. These data suggest that perhaps the intracellular Ca2+ concentration is regulated differently in young and senescent cells. Indeed, the cell cycle regulation of calmodulin may be uncoupled from the cell cycle regulation of calmodulin mRNA. This difference could provide one mechanism for the failure of senescent cells to synthesize DNA following mitogenic stimulation. PMID- 8482348 TI - Differential effects of TPA and pristane on gene expression and transformation in mouse epidermal cells. AB - The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) or 2,6,10,14 tetramethylpentadecane (pristane) on gene expression and transformation were examined using two clones (P+, TPA transformation sensitive and P-, TPA resistant) of the mouse epidermal cell line JB6. Results from transformation studies indicated pristane was more efficient, i.e., lower concentrations were required to elicit an equivalent response, in transforming the P+, but not the P , clone of JB6 compared to TPA. Furthermore, results from these studies demonstrated either TPA or pristane was effective in the transactivation of the chloramphenicol acetyltransferase gene under the regulatory control of most viral promoter/enhancer elements transfected into the P+, but not the P-, clone of JB6. However, if a consensus cAMP response element was linked to the simian virus 40 early promoter, pristane activation was observed in both P+ and P- cells. The differential effects of these two compounds suggest that while they have similar characteristics, they may utilize different pathways to elicit their effects. PMID- 8482349 TI - Adhesion and activation of human neutrophils onto collagen chains separated by electrophoresis. AB - After separation of the various alpha chains of the collagens by SDS-PAGE, the binding of polymorphonuclear neutrophils (PMN) to these chains was detected by a double-antibody technique and the activation of PMN by nitro blue tetrazolium. All of the alpha chains tested were able to bind PMNs. The alpha 1 chain of type I collagen activated the PMN when it had not been treated with pepsin. Pepsinized types II and VI collagens did not activate PMN. The pepsinized alpha 1(III) chains and all three alpha chains from pepsinized type V collagen were able to activate PMN. PMID- 8482350 TI - Ultrastructural distribution of DNA within the ring-shaped nucleolus of human resting T lymphocytes. AB - The precise distribution of DNA within the resting human T lymphocyte nucleolus has been investigated, at the ultrastructural level, by cytochemical and molecular immunocytochemical techniques. The nucleolus is partially enveloped by a layer of condensed chromatin which, at several places, penetrates into the nucleolar body until in close contact with the fibrillar centers. Morphometric analysis reveals that 32% of the fibrillar center surface is essentially occupied by condensed chromatin. Using the in situ terminal deoxynucleotidyl transferase immunogold procedure for detecting DNA, we further show that evident label is exclusively found over the condensed chromatin and over the fibrillar centers, whereas no significant label is detected over the dense fibrillar component of the nucleolus. PMID- 8482351 TI - Cytoplasmic localization and nuclear transport of cofilin in cultured myotubes. AB - We used immunofluorescence methods to examine the cellular distribution of cofilin in chicken myotubes in primary culture. Cofilin showed mainly diffuse distribution in the cytoplasm except for rather strong staining around the nuclei and faint striated patterns along myofibrils, but did not stain inside the nuclei. Neither stress fiber-like structures nor myofibrils were clearly stained. In the presence of 10% dimethyl sulfoxide (DMSO), intranuclear actin-cofilin rods, which were composed of alpha-actin isoform and cofilin, were formed in all the nuclei of individual myotubes. In the cofilin sequence, a putative nuclear localization signal (NLS) was observed. We examined the NLS activity of this portion by using a synthetic peptide corresponding to the putative NLS. When the NLS peptide conjugated with bovine serum albumin was microinjected into the cytoplasm of myotubes, it was rapidly accumulated into the nuclei. The same result was obtained with in vitro a nuclear protein import assay system with digitonin-permeabilized myotubes. Therefore, we suggest that this portion is responsible for the nuclear transport of cofilin. In myotubes, the majority of cofilin was present in an unphosphorylated form and this form remained unchanged after the DMSO treatment. Thus, we suggest that the phosphorylation of cofilin itself is not directly involved in its nuclear transport at least in myotubes. PMID- 8482352 TI - T lymphocyte infiltration of two- and three-dimensional collagen substrata by an adhesive mechanism. AB - Lymphocytes were plated on two-dimensional (2D) and three-dimensional (3D) collagen substrata and their distribution and behavior determined using light and scanning electron microscopy. When allowed to settle on 2D collagen substrate T lymphocytes "rapidly" attached and penetrated and thus virtually never remained attached on top of the collagen. As a consequence of this penetration the cells appeared below the collagen. In contrast to lymphocytes, fibroblasts and macrophages allowed to settle on 2D collagen did not penetrate but underwent cytoplasmic spreading on top of the collagen. Lymphocyte attachment and penetration of 2D collagen was specifically inhibited by monoclonal antibodies to beta 1-integrins, indicating that the process depends on molecular adhesion to the collagen. The penetration of 2D collagen appeared to consist of tight binding of collagen fibers to the cells, local reorganization of the collagen carpet, and redistribution of the cell-attached collagen fibers from the "lower" to the "upper" pole/surface of the lymphocyte. Lymphocyte infiltration of 3D collagen substrata was also specifically inhibited by monoclonal antibodies to beta 1 integrins. During the infiltration of 3D collagen lymphocytes exhibited collagen fibers attached to their surface and seemed to provoke perturbation of the collagen. These results show that T lymphocytes are programmed to penetrate and perturb 2D and 3D collagen substrata by a mechanism dependent on adhesive interaction. However, deattachment tends to counteract persistent binding of the cells to 2D collagen. PMID- 8482353 TI - Chondrogenesis in chick limb bud mesodermal cells: reciprocal modulation by activin and inhibin. AB - Activin and inhibin are members of the transforming growth factor-beta superfamily sharing a common beta-subunit, but with opposite biological activities on the release of follicle-stimulating hormone from pituitary. Recent studies have demonstrated that activin is the long sought after mesoderm induction factor in amphibians. To determine if activin and inhibin affect the proliferation and differentiation of chick limb bud mesodermal cells during cartilage formation of the limb, recombinant human activin A and inhibin A were tested on stage 24 chick limb bud mesodermal cells. The results showed that activin A has an inhibitory effect on chondrogenic differentiation, as indicated by Alcian blue staining and decreased [35S]sulfate incorporation into proteoglycans. In addition, the expression of type II collagen mRNA, a specific phenotypic marker of cartilage, was greatly inhibited when cultures were exposed to activin A for 5 days at a dose of 10 ng/ml. In contrast, inhibin A stimulated cartilage formation, as indicated by increased expression of type II collagen mRNA and synthesis of proteoglycans. These results imply that activin A and inhibin A can modulate chondrogenesis during differentiation of limb bud cells in culture. PMID- 8482354 TI - 70-kDa heat-shock cognate protein colocalizes with karyophilic proteins into the nucleus during their transport in vitro. AB - Recently, we showed that antibodies against 70-kDa heat-shock cognate 66otein (hsc70) inhibit nuclear transport of karyophilic proteins in vivo. In this study, we examined the involvement of hsc70 in nuclear transport using a digitonin permeabilized cell-free transport system. Depletion of the cytosolic extract required for nuclear transport of hsc70 by incubation with anti-hsc70 antibodies reduced the nuclear transport activity significantly, and addition of purified hsc70 to the depleted extract restored the transport activity. We examined the localization of hsc70 during nuclear transport in vitro by indirect immunofluorescence studies. Hsc70 accumulated in the nucleus when bovine serum albumin (BSA) conjugated to SV40 large T-antigen nuclear localization signal (NLS) peptides (T-BSA) or nucleoplasmin was added exogenously to the cytosolic extract, but not when BSA conjugated to transport-incompetent point-mutated NLS peptide was added. This karyophilic protein-dependent accumulation of hsc70 was dependent on the cytosolic extract, temperature, and ATP and was sensitive to wheat germ agglutinin. Addition of excess unlabeled T-BSA to the cytosolic extract competitively inhibited the nuclear accumulation of fluorescently labeled T-BSA or nucleoplasmin, but did not affect accumulation of hsc70 into the nucleus. These results show that hsc70 is required for nuclear transport and that it is colocalized with karyophilic proteins during their active import into the nucleus in vitro. PMID- 8482355 TI - Identification of DNA-binding proteins in the parasitic protozoan Crithidia fasciculata and evidence for their association with the mitochondrial genome. AB - The single mitochondrion of trypanosomatid protozoans such as Crithidia fasciculata has a large and complex network of AT-rich DNA called kDNA. Little is known about proteins involved in the packaging and morphogenesis of this network. I report the purification of a protein fraction from this parasite which preferentially retained kDNA in the gel slot during electrophoresis. The proteins had approximate molecular weights of 22, 21, 17.5, 16.5, 15, and 13 kDa. They copurified with mitochondrial DNA, parts of which they protected from nuclease attack. The proteins resembled histones but they also differed from histones in significant ways. Immunological evidence showed that the proteins were enriched in a mitochondrial fraction, implying their association with kDNA in vivo. PMID- 8482356 TI - Modulation of growth of vascular smooth muscle cells by activin A. AB - Activin A is a homodimeric protein structurally related to transforming growth factor-beta. The present study was conducted to examine the effect of activin A on the growth of rat vascular smooth muscle cells (VSMC) in culture. When serum deprived cells were incubated with activin A, nuclear labeling of bromodeoxyuridine occurred after a 12-h lag period. The effect of activin A on nuclear labeling was dose-dependent, being maximal at 10(-9) M. Activin A also increased the number of VSMC after 30 h of incubation. Insulin-like growth factor 1 (IGF-1) had only a small effect on nuclear labeling by itself but the effects of IGF-1 and activin A were additive. When quiescent VSMC were treated with activin A for 4 h, the effect of subsequent IGF-1 was markedly enhanced. Furthermore, activin A induced an autocrine production of IGF-1 in VSMC. In contrast to these positive effects on cell growth, activin A was rather inhibitory to the action of IGF-1 in activin-primed cells. In addition, activin A inhibited platelet-derived growth factor-induced nuclear labeling. These results indicate that activin A modifies growth of VSMC by complex mechanisms involving autocrine production of IGF-1 and modification of the action of IGF-1. PMID- 8482357 TI - A light microscope study of linker histone distribution in rat metaphase chromosomes and interphase nuclei. AB - Several subtypes of the linker histone H1 are present in normal rat kidney epithelial cells (NRK-52E). Although H1 is essential in nucleosome and chromatin packaging or condensation, the unique functions of these very basic proteins are largely unknown. There has been much speculation on the role of each H1 variant on developmentally regulated or tissue specific gene expression. We have examined the global distribution of several H1 subtypes on metaphase chromosomes in an attempt to uncover large-scale differences in chromatin condensation. Polyclonal antibodies raised against HPLC-purified rat H1 subtypes revealed a pattern much like G or Q bands for all H1 variants tested on chromosomes harvested with either aqueous or organic spreading methods. H1(0), a less abundant form of H1, may be associated with terminally differentiated or senescent cells. In cultures treated to induce higher levels of H1(0) there were no visible differences at the light microscope level in the antibody banding pattern between induced and noninduced cells. The distributions of H1 subtypes on chromosomes may be visible in different tissues when viewed at higher magnifications. While chromosome patterns were consistent with the antibodies tested, the interphase nuclei displayed clear differences. An epitope specific for anti-H1A antibody is present in the nuclear envelope and is possibly used for chromosomal location or anchorage. Anti-H1B antibody did not specifically label the nuclear envelope, nor did anti-H1(0) antibody. Highly concentrated regions of H1(0) surround the nucleoli, possibly indicating a cluster of genes that are poised for transcription. PMID- 8482358 TI - Insulin induces an unmasking of the carboxyl terminus of G(i) proteins in rat adipocytes. AB - Several groups have shown a relationship between the insulin receptor and inhibitory G proteins, G(i). An antisera, 8729, to a peptide sequence (KNNLKDCGLF) corresponding to the carboxyl termini of G(i)alpha subunits was used to investigate this relationship by immunoelectron microscopy. Rat adipocytes were incubated in the absence or presence of 100 ng/ml insulin for 1 h and fixed for immunoelectron microscopy. Insulin-treated adipocytes stained with 8729 were labeled at the cell surface at a much higher density than control adipocytes. Subcellular fractionation of insulin-treated and control cells was followed by PAGE and Western blots of the plasma membrane and low-density microsomes with 8729. The density of the bands did not change in response to insulin treatment. Antibodies to noncarboxyl terminus sequences of the alpha subunit were used for immunoelectron microscopy and no difference was noted between insulin-treated and control adipocytes. These results indicated that 8729 was detecting a conformational change in the structure of G(i)alpha subunit in the plasma membrane in response to insulin. This unmasking of the carboxyl terminus was also seen in response to treatment with phenylisopropyladenosine and prostaglandin E2. Pertussis toxin-catalyzed ADP ribosylation also unmasked the carboxyl terminus. In contrast, isoproterenol, an agonist of stimulatory G proteins (Gs), did not induce an unmasking of the carboxyl terminus. These results support the hypothesis that some of insulin's effects are mediated through G(i) proteins in adipocytes. PMID- 8482359 TI - Growth control in a human colon carcinoma cell line mediated by cell-associated transforming growth factor-alpha (TGF alpha). AB - Transforming growth factor-alpha (TGF alpha) is able to elicit growth in many target cells expressing a functional epidermal growth factor (EGF) receptor. Other laboratories have reported that the TGF alpha precursor polypeptide (proTGF alpha) is inefficiently cleaved from many target cells, resulting in accumulation of proTGF alpha on the cell surface. Since it has been shown that noncleavable, mutated cell-associated TGF alpha can stimulate cell growth on receptor-bearing adjacent cells, we have tried to determine whether cell-associated TGF alpha populations might be involved in supporting autonomous cell growth regulatory mechanisms in a human colon carcinoma cell line, HCT116. To address this question, the levels of secreted and nonsecreted TGF alpha produced were determined. Cells grown to medium cell density (40-60% confluent) expressed the greatest percentage of cell-associated TGF alpha (50%). Incubation of HCT116 cells with 0.1 U/ml porcine pancreatic elastase resulted in the release of 67% of the cell-associated TGF alpha into their medium and caused the treated cells to acquire a newly established growth sensitivity to exogenous TGF alpha at a ligand concentration of 1.0 nM. Western blot analysis of EGF receptor phosphotyrosine levels showed a decrease in phosphotyrosine content after elastase treatment. Phosphotyrosine content was restored to basal levels if elastase treatment was followed by addition of exogenous TGF alpha or EGF. These results suggest that HCT116 cells use a "closed" autocrine loop between cell-associated TGF alpha species and their EGF receptor to stimulate their cell growth. PMID- 8482360 TI - Interleukin-1 differentially modulates chondrocyte expression of cyclooxygenase-2 and phospholipase A2. AB - Interleukin-1 beta (IL-1) increases the synthesis of prostaglandins as well as the expression of synovial fluid phospholipase A2 (PLA2) mRNA and activity by chondrocytes. In order to examine the potential involvement of cyclooxygenase in the induction of prostaglandins by IL-1, the effect of IL-1 on rabbit articular chondrocyte expression of cyclooxygenase enzymes was investigated. By Northern analyses, mRNA for cyclooxygenase-2 (COX-2) was found to be constitutively expressed, and its expression was increased in cultures treated for 24 h with IL 1 (100 ng/ml). Cyclooxygenase-1 mRNA was not detected in control or IL-1-treated cultures. IL-1 caused a concentration-dependent increase in steady-state levels of COX-2 message as assessed by slot-blot analyses. Half-maximal induction of the COX-2 message levels was estimated to require 1.2 ng/ml IL-1. In duplicate slot blots probed with a cDNA for synovial fluid PLA2, half-maximal induction of PLA2 mRNA was estimated to require 0.15 ng/ml IL-1, approximately 10-fold less IL-1 than required for COX-2. In addition, maximal increase in COX-2 message levels was only 3-fold as compared with a 13-fold induction of PLA2. No change in message levels for the intracellular protein, actin, was found between control and experimental cultures. Cycloheximide enhanced COX-2 transcript levels, but did not modulate IL-1 induction of COX-2. Actinomycin D did not inhibit IL-1 augmentation of COX-2 mRNA levels; whereas, induction of PLA2 mRNA levels was completely inhibited, implicating transcriptional mechanisms in the induction of PLA2 but not COX-2 mRNA. These data demonstrate that chondrocyte expression of COX-2 and synovial fluid PLA2 are differentially modulated by IL-1. PMID- 8482361 TI - Transcriptional activation of type I collagen genes by ascorbic acid 2-phosphate in human skin fibroblasts and its failure in cells from a patient with alpha 2(I) chain-defective Ehlers-Danlos syndrome. AB - L-Ascorbic acid 2-phosphate (Asc 2-P), a long-acting vitamin C derivative, stimulated transcription of genes for pro alpha 1(I) and pro alpha 2(I) collagen in normal human skin fibroblasts after 8 h of treatment in the absence or in the presence of cycloheximide, indicating Asc 2-P stimulates transcription of type I collagen genes in the absence of protein synthesis. The transcriptional rate in these cells reached the maximum value after 40 h of treatment, and at that time it was three to four times higher than that of the control cells cultured in the absence of Asc 2-P. Steady-state levels of mRNAs for pro alpha 1(I) and pro alpha 2(I) chains were also increased to be three to four times higher than the control levels by treatment of the cells with Asc 2-P for 72 h. When the fibroblasts obtained from a patient with Ehlers-Danlos syndrome were treated with Asc 2-P, the derivative also stimulated transcription of the gene for pro alpha 1(I) chain and accumulation of mRNA for pro alpha 1(I) chain. On the other hand, Asc 2-P failed to stimulate transcription of the pro alpha 2(I) gene or an increase in mRNA for pro alpha 2(I) chain. Sodium ascorbate showed effects quite similar to those of Asc 2-P, when fibroblasts obtained from a normal control or the patient were cultured for 16 h with it. These results indicate the existence of cis regulatory elements responsible for transcriptional activation by Asc 2-P or ascorbic acid in pro alpha 1(I) and pro alpha 2(I) genes of normal fibroblasts. These data also suggest some defect(s) of these elements in the pro alpha 2(I) gene of the patient with Ehlers-Danlos syndrome. PMID- 8482362 TI - Monoclonal antibodies targeted against the C-terminal domain of dystrophin or utrophin. AB - The structure-function relationships of dystrophin, a protein which is absent or defective in patients with Duchenne or Becker muscular dystrophies, and utrophin can only be compared if specific antibodies are produced. We expressed C-terminal parts of dystrophin and utrophin in expression vectors. Mice were immunized with recombinant proteins and 26 monoclonal antibodies were produced and analyzed. Their respective epitopes were determined using other overlapping recombinant products. We observed antibody specificity towards 400 kDa dystrophin and/or utrophin protein bands, either by Western blot analysis or immunodetection in human skeletal (quadriceps) and smooth (uterus) muscles. These antibodies have been used to compare the relative abundance of both dystrophin and utrophin relative to the structures analyzed. PMID- 8482363 TI - Role of Lys-110 of human NADH-cytochrome b5 reductase in NADH binding as probed by site-directed mutagenesis. AB - Lys-110 of human NADH-cytochrome b5 reductase was replaced by Ala, Met, or Arg by site-directed mutagenesis to evaluate the role of the residue. Km values of purified Lys-110-->Ala and Lys-110-->Met mutants for NADH were approximately 200 fold and 1,100-fold higher than that of the wild-type, respectively, while the value of the Arg mutant was almost the same as that of the wild-type. These results indicate that the positive charge at position 110 is important for NADH binding. The kcat value of Lys-110-->Ala was not affected, indicating that the residue only participates in the binding process in the reaction by forming an ionic interaction with phosphoryl group of NADH. PMID- 8482364 TI - Hepatic apolipoprotein B synthesis in copper-deficient rats. AB - The present study was designed to examine if induction of apolipoprotein B synthesis is associated with hypercholesterolemia in copper-deficient rats. This hypercholesterolemia mainly resides in an increase in the HDL-1 and LDL and is associated with a significant increase in plasma apoB concentration. Liver apoB mRNA levels were not significantly modified in deficient animals as compared to control rats. Studies on liver apolipoprotein synthesis indicated that apoB100 synthesis was increased in deficient animals whereas apoB48 synthesis was unchanged. Thus, it appears that the increase in apoB synthesis in the liver of copper-deficient rats occurs at the posttranscriptional level. The selective increase in apoB100 synthesis indicates the possible impact of this deficiency on the editing of apoB. An increase in apoB100 synthesis by the liver in copper deficient rats may significantly contribute to the increase in plasma concentration of LDL. PMID- 8482365 TI - The VP35 and VP40 proteins of filoviruses. Homology between Marburg and Ebola viruses. AB - The fragments of genomic RNA sequences of Marburg (MBG) and Ebola (EBO) viruses are reported. These fragments were found to encode the VP35 and VP40 proteins. The canonic sequences were revealed before and after each open reading frame. It is suggested that these sequences are mRNA extremities and at the same time the regulatory elements for mRNA transcription. Homology between the MBG and EBO proteins was discovered. PMID- 8482366 TI - Monoclonal anti-biotin antibodies simulate avidin in the recognition of biotin. AB - The sequence of the VH gene of a monoclonal anti-biotin antibody was determined. Biotin-binding motifs, similar to those in avidin and streptavidin, were identified in complementary determining regions 2 and 3, suggesting that natural selection of functional motifs may occur in unrelated protein types. PMID- 8482367 TI - Phosphorylation of mitochondrial proteins in bovine heart. Characterization of kinases and substrates. AB - Protein phosphorylation by [gamma-32P]ATP in total extract and subfractions of bovine heart mitochondria has been studied. The results show that, in addition to pyruvate dehydrogenase, three mitochondrial proteins, with molecular weights of 44,000, 39,000 and 31,000 Da, are phosphorylated by a cAMP-independent mitochondrial protein kinase. Three other proteins associated with mitochondria, with molecular weights of 125,000, 19,000 and 6,500 Da, are phosphorylated by the cytoplasmic cAMP-dependent protein kinase (kinase A). PMID- 8482368 TI - Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-Caldesmon. AB - h-Caldesmon in vascular smooth muscle is phosphorylated in response to pharmacologic stimulation. Although many kinases phosphorylate h-caldesmon, in vitro, the responsible kinase in intact tissue is unknown. The sites of phosphorylation in caldesmon from intact canine aortas have recently been identified and are consensus sequences for a proline-directed protein kinase. In this study, we investigated the phosphorylation of h-caldesmon by mitogen activated protein kinase (MAPK). Purified, recombinant MAPK phosphorylated porcine stomach h-caldesmon to a stoichiometry approaching 2 mol phosphate/mol protein. Phosphorylated h-caldesmon was subjected to proteolysis and the phosphopeptides were purified by high performance liquid chromatography. Two major phosphopeptides were identified and sequenced. These two peptides, VTS*PTKV and S*PAPK, were identical to the sequences of the sites phosphorylated in intact tissue. Antibodies to several enzymes implicated in the cascade of activation of MAPK were used to evaluate vascular smooth muscle by Western blotting. All components were found to be present. These data suggest that MAPK can function as a 'caldesmon kinase' in vascular smooth muscle. PMID- 8482369 TI - Starvation effect on rat kidney peroxisomal and microsomal fatty acid oxidation. A comparative study between liver and kidney. AB - Microsomal lauric acid 12-hydroxy lauric acid (omega)-hydroxylation and fatty acid peroxisomal beta-oxidation were studied in kidney tissue from starved rats. Starvation increased the microsomal omega-hydroxylation and peroxisomal beta oxidation of fatty acids with a high correlation between both processes. Earlier, we reported similar results in liver. Our results support the hypothesis that the role of microsomal fatty acids omega-hydroxylation is the generation of substrate for peroxisomal beta-oxidation, with the final purpose of contributing to a catabolic or gluconeogenic pathway from fatty acids. PMID- 8482370 TI - Structural modifications associated with the change in Ca2+ sensitivity on activation of m-calpain. AB - Autolysis of the Ca(2+)-dependent cysteine protease m-calpain involves cleavage of the large (80 kDa) and small (30 kDa) subunits of the enzyme, and an increase in Ca2+ sensitivity. The appearance of increased Ca2+ sensitivity was found to correlate with the cleavage of the large subunit after residue 9. PMID- 8482371 TI - Age-dependent deamidation of alpha B-crystallin. AB - Bovine and human alpha B-crystallin undergo deamidation upon aging in the lens. In bovine alpha B-crystallin, the specific site of deamidation has been identified by peptide mapping after tryptic digestion. Asn-146 was found to be subject to deamidation, whereas the only other asparagine residue, at position 78, is not affected. Asn-146 is flanked at the carboxylic side by a glycyl residue. Yet, the rate of in vivo deamidation is low. In vitro studies reveal that the deamidation is accompanied by significant racemization, indicating that the deamidation proceeds via formation of a succinimide intermediate. PMID- 8482372 TI - Presence of the brown fat-specific mitochondrial uncoupling protein and iodothyronine 5'-deiodinase activity in subcutaneous adipose tissue of neonatal lambs. AB - Subcutaneous adipose tissue of neonatal lambs has been examined for the presence of markers diagnostic of thermogenic brown fat. Uncoupling protein, uncoupling protein mRNA, and iodothyronine 5'-deiodinase activity were each detected in subcutaneous adipose tissue, as well as in the major internal fat depot (perirenal), of newborn lambs. These brown fat markers were not present, however, in adipose tissue of adult sheep. It is concluded that subcutaneous fat in newborn lambs is functionally 'brown', and similar to the internal fat; subcutaneous and internal adipose tissues follow a similar developmental path- from 'brown' to 'white'. PMID- 8482373 TI - Procathepsin L-specific antibodies that recognize procathepsin L but not cathepsin L. AB - Procathepsin L was purified to apparent homogeneity from the culture medium of v Ha-ras transformed NIH3T3 (Ras-NIH) cells in three steps; anion-exchange chromatography, gel filtration, and re-gel filtration. SDS-PAGE analyses revealed that the purified samples contained only the precursor form, procathepsin L, but not the mature enzyme, cathepsin L. Antibodies against purified procathepsin L were raised. These recognized both rat cathepsin L and the purified procathepsin L. To isolate procathepsin L-specific antibodies that did not recognize cathepsin L, sequential affinity chromatography procedures were carried out. Immunoblot analyses showed that the procathepsin L-specific antibodies recognized only procathepsin L, but not cathepsin L. PMID- 8482374 TI - The role of protein tyrosine phosphatases in density-dependent growth control of normal rat kidney cells. AB - In normal rat kidney cells protein tyrosine phosphatases (PTPases) play a role in attaining density-dependent growth arrest after stimulation with mitogens. The PTPase inhibitor sodium orthovanadate prevents density-dependent growth inhibition of EGF-treated cells and mimicks in that respect the action of TGF beta and retinoic acid. However, enhanced PTPase activity is not obligatory for maintaining cells in a density-arrested state. In contrast to TGF beta and retinoic acid, vanadate is unable to restimulate density-inhibited cells, indicating that different mechanisms are operating. Yet, vanadate is strongly potentiating the effect of low concentrations of TGF beta but not of retinoic acid, implicating that tyrosine phosphorylation is linked to TGF beta action and that PTPase may represent a negative control element in the TGF beta signaling pathway. PMID- 8482375 TI - Identification of phytanoyl-CoA ligase as a distinct acyl-CoA ligase in peroxisomes from cultured human skin fibroblasts. AB - Phytanic acid accumulates in excessive amounts in Refsum disease, a rare neurological disorder, due to a defect in its alpha-oxidation enzyme system in peroxisomes. The activation of phytanic acid to phytanoyl-CoA by phytanoyl-CoA ligase is a prerequisite for its alpha-oxidation. The studies described in this manuscript report that phytanoyl-CoA ligase in peroxisomes is an enzyme distinct from the previously reported acyl-CoA ligases. PMID- 8482376 TI - The antigenic domain of flagellin from S. paratyphi shares a structural fold with subtilisin. AB - Bacterial flagellin has two domains: the polymerizing domain consisting of N- and C-terminal regions which are partly disordered in the monomeric state; and the central antigenic domain with compact globular structure. The polymerizing domain is highly conserved in flagellins from different species but the antigenic domain is diverse in sequence and size. Whereas the former has direct functional significance for bacterial motility, the latter has not been identified as having a specific function except for defining the distinct serotype of the bacterium. The sequence alignment of flagellin from S. paratyphi with proteins of known three-dimensional structure reveals significant homology of the central 265 residue stretch with the bacterial serine protease, subtilisin. This homology is evident also in the comparison of the predicted secondary structure of flagellin with the observed secondary structural features in subtilisin. The deletions/insertions arising due to optimal alignment of the two proteins occur on the surface loops in the structure. Thus, a domain of S. paratyphi flagellin and subtilisin appear to have similar structural folds. PMID- 8482377 TI - Protein kinase C isoenzymes in human neuroblasts. Involvement of PKC epsilon in cell differentiation. AB - Although neuronal cells are a major target of phorbol ester action, the activity of the various protein kinase C (PKC) isoenzymes have not been studied in detail in human neuroblasts. Differentiation of the LAN-5 human neuroblastoma cell line by interferon-gamma (IFN-gamma) is accompanied by a twofold increase in PKC activity. Since PKC is a multigene family, we investigated which isoforms were expressed in control and differentiated cells, and which of these isoenzymes is involved in neuronal differentiation. We found that: (1) PKC activity is higher in differentiated than in undifferentiated cells; (2) RT-PCR analysis showed the expression of mRNA for PKC alpha, -gamma, -delta, -epsilon and -zeta and the absence of mRNA for beta in untreated LAN-5 cells; (3) Western blot evaluation with PKC isoform-specific antibodies showed the same pattern of PKC expression in non-differentiated cells; (4) Expression of PKC epsilon mRNA was significantly enhanced by IFN-gamma-induced differentiation, while the other isoforms were not affected; (5) Differentiation of LAN-5 cells with IFN-gamma or retinoic acid induced overexpression of the PKC epsilon protein, while inhibition of cell proliferation by fetal calf serum starvation was without effect. These findings suggest that expression of PKC epsilon isoform is tightly coupled with neuronal differentiation and may play a role in the maintenance of the differentiated state. PMID- 8482378 TI - Biochemical and immunological evidence that an acidic domain of hsp 90 is involved in the stabilization of untransformed glucocorticoid receptor complexes. AB - Polyclonal antibodies (AS 232-266) have been raised against the 232-266 amino acid sequence of the mouse hsp 84. This sequence possesses 54% acidic residues. AS 232-266 react with both the denatured and the free native murine hsp 84, but not with the bound hsp 84 present in the untransformed glucocorticoid receptor complexes (GR). Both AS 232-266 and peptide 232-266 were shown to decrease [3H]dexamethasone binding by GR. Moreover synthetic peptide 232-266, when added to 7 nm untransformed GR, convert them into 5 nm hsp 84-free GR. Taken together these data suggest that the acidic 232-266 sequence of hsp 84 is involved in the stabilization of the hsp 84-GR interaction, which is known to result in 7 nm complex formation and in GR ligand binding activity improvement. Both peptide 232 266 and AS 232-266 destabilize this interaction. PMID- 8482379 TI - cDNA cloning of a new type of subunit of mammalian proteasomes. AB - The primary structure of a new type of subunit (RN3) of rat proteasomes (multicatalytic proteinase complexes) has been determined from the nucleotide sequence of the cDNA. The cDNA encodes a protein of 232 amino acids but the directly determined N-terminal amino acid sequence suggests that the subunit is post-translationally processed to a M(r) = 24k form. Sequence alignments reveal a similarity of RN3 to other proteasome subunits. It can be designated a B-type proteasomal subunit but is not closely related to the beta subunit of the archaebacterial proteinase or to other members of the B group. PMID- 8482380 TI - Three-dimensional model of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase and relationships to the NADP(+)-dependent enzyme (carbonyl reductase). AB - Modelling the amino acid sequence of NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase into the three-dimensional structure of 3 alpha/20 beta hydroxysteroid dehydrogenase shows that these two enzymes, as well as the NADP(+) linked prostaglandin dehydrogenase (identical to carbonyl reductase) have similar conformations, in spite of very limited sequence identity (23-28%). Conservation of tertiary structures is greatest over the first two thirds of the polypeptide chains, where the typical NAD+ binding fold is retained, including the five first beta-strands, with only two short deletions or insertions up to residue 147. The remaining thirds of each of the prostaglandin dehydrogenases have significantly different architecture, including insertions that may contribute to enzyme specificity, and, except for an additional helix (alpha G), are difficult to model. Active site relationships can be evaluated and subunit interactions predicted, suggesting that the alpha E + alpha F two-helix surface constitutes the major subunit interacting area, forming a dimeric unit in the oligomeric enzymes. PMID- 8482381 TI - The local information content of the protein structural database. PMID- 8482382 TI - Endothelin-1 stimulated phospholipase D in A10 vascular smooth muscle derived cells is dependent on tyrosine kinase. Evidence for involvement in stimulation of mitogenesis. AB - The mechanism whereby endothelin stimulates mitogenesis of vascular smooth muscle cells is not understood. Here we show that endothelin-1 stimulates phospholipase D by a protein kinase C and tyrosine kinase dependent mechanism, and present evidence that implicate the phosphatidic acid formed by phospholipase D in the mitogenic response. PMID- 8482383 TI - Mycalolide-B, a novel and specific inhibitor of actomyosin ATPase isolated from marine sponge. AB - A toxin isolated from marine sponge, mycalolide-B, inhibited smooth muscle contractions without changing cytosolic Ca2+ levels. It also inhibited Ca(2+) induced contraction in permeabilized smooth muscles. In native actomyosin prepared from chicken gizzard, mycalolide-B inhibited superprecipitation and Mg(2+)-ATPase activity stimulated by Ca2+ without changing myosin light chain phosphorylation. In the permeabilized muscle and native actomyosin preparation thiophosphorylated with ATP gamma S, mycalolide-B inhibited ATP-induced contraction and Mg(2+)-ATPase activity, respectively, in the absence of Ca2+. Mycalolide-B also inhibited Mg(2+)-ATPase activity of skeletal muscle native actomyosin. Mycalolide-B had no effect on calmodulin-stimulated (Ca(2+)-Mg2+) ATPase activity of erythrocyte membranes. These results suggest that mycalolide-B selectively inhibits actin-myosin interaction. PMID- 8482384 TI - Homology of the NifS family of proteins to a new class of pyridoxal phosphate dependent enzymes. AB - Iterative profile sequence analysis reveals a remote homology of peroxisomal serine-pyruvate aminotransferases from mammals to the small subunit of soluble hydrogenases from cyanobacteria, an isopenicillin N epimerase, the NifS gene products from bacteria and yeast, and the phosphoserine aminotransferase family. All members of this new class whose function is known are pyridoxal phosphate dependent enzymes, yet they have distinct catalytic activities. Upon alignment, a lysine around position 200 remains invariant and is predicted to be the pyridoxal phosphate-binding residue. Based on the detected homology, it is predicted that NifS has also a pyridoxal phosphate-dependent serine (or related) aminotransferase function associated with nitrogen economy and/or protection during nitrogen fixation. PMID- 8482385 TI - An X-ray absorption study of the reconstitution process of bovine Cu,Zn superoxide dismutase by Cu(I)-glutathione complex. AB - The Cu(I)GSH complex has recently been shown to be a good candidate for delivering copper to the active site of Cu-free Cu,Zn superoxide dismutase both in vivo and in vitro. In this work X-ray absorption spectroscopy has been used to characterize the Cu(I)GSH complex and to follow in vitro the reconstitution of Cu,Zn superoxide dismutase from the copper-free protein and this complex. The results obtained indicate that the copper is directly transferred as Cu(I) from the GSH complex into the empty copper binding site. No evidence has been obtained for a ternary complex in which the metal is bound to both GSH and the protein. PMID- 8482386 TI - Electron transfer in pheophytin a-modified reaction centers from Rhodobacter sphaeroides (R-26). AB - The major part (> 90%) of bacteriopheophytin a in reaction centers (RCs) of Rhodobacter sphaeroides was substituted by plant pheophytin a. In modified RCs the photochemical formation of P+Qa- occurs with with a quantum efficiency of 79%. The intermediary state P+I- displayed a recombination time constant of 1.5 ns, and the electron transfer from I- to Qa was characterized by a time constant of 540 ps. On the basis of spectral properties of P+I- for native and modified RCs, it was suggested that bacteriopheophytin, as well as bacteriochlorophyll monomers located in L protein branch, have a transition at 545 nm with approx. equal extinction coefficients. Accordingly, the state P+I- in modified RCs is proposed to consist of a thermodynamic mixture of P+BL- (approximately 80%) and P+Phe- (approximately 20%). PMID- 8482387 TI - A 19F NMR study of the interaction of 3-fluoro-4-demethoxydaunomycin with the hexanucleotide d(TCCGGA)2. AB - 19F NMR spectroscopy has been used to study the binding of the fluorinated anthracycline 3-fluoro-4-demethoxydaunomycin with the hexanucleotide d(TCCGGA)2. In the spectrum of the 1:1 anthracycline-d(TCCGGA)2 complex four resonances of approximately equal intensity were observed. This indicated that 4 demethoxydaunomycin intercalated at all possible sites with similar affinity. This suggests that the specific high affinity binding sites that are observed in anthracycline-DNA footprinting experiments are strongly regulated by the local DNA conformation. PMID- 8482388 TI - B16-G4F mouse melanoma cells: an MSH receptor-deficient cell clone. AB - The two mouse melanoma cell lines B16-F1 and B16-G4F retain their melanogenic capacity when cultured in vitro. Melanotropic peptides such as alpha-melanocyte stimulating hormone (alpha-MSH) induce formation and release of melanin pigment in B16-F1 cells. In contrast, B16-G4F cells do not respond to alpha-MSH. Using receptor-binding analysis and photoaffinity crosslinking we demonstrate that the lack of response of B16-G4F cells to alpha-MSH is due to the absence of functional MSH receptors from the cell surface. Northern blot analysis of receptor mRNA revealed that MSH receptor mRNA is not expressed in B16-G4F cells. These cells represent a new tool for the study of signal pathways related to the control of melanogenesis in melanoma cells. PMID- 8482389 TI - The structure of human carbonic anhydrase II in complex with bromide and azide. AB - The three-dimensional structure of human carbonic anhydrase II complexed with azide and with bromide was investigated crystallographically. Both of these non protonated inhibitors replace the zinc and the 'deep' water, two catalytically important water molecules in the active site of the molecule. Both the azide and the bromide ions bind in a distorted tetrahedral manner 0.4 and 1.1 A from the zinc water position, respectively, but are in close contact (2.0 and 2.6 A, respectively) with the zinc ion. PMID- 8482390 TI - Purification and characterization of the cystinyl bond cleaving yeast aminopeptidase yscXVI. AB - Aminopeptidase yscXVI was purified from the yeast Saccharomyces cerevisiae. By SDS-PAGE the enzyme has a molecular weight of 45,000 Da, and in chromatofocusing, elution was observed at pH 6.2. The synthetic substrate cystinyl-4-nitroanilide (Km 22.5 microM, Vmax 12.9 mU/mg) is cleaved most efficiently in the pH range 7 8. Besides cleaving this standard substrate, aminopeptidase yscXVI acts on several other 4-nitroanilide substrates with unsubstituted N-terminal L-amino acids. Highest hydrolysis rate was measured with Lys-4-nitroanilide and Leu-4 nitroanilide. The activity of aminopeptidase yscXVI is abolished by chelating agents and restored by Zn2+, Mn2+ and Co2+ ions. Bestatin and amastatin are both strong inhibitors of the enzyme, with Ki values of 0.53 microM and 0.93 microM, respectively. Aminopeptidase yscXVI is detectable in the logarithmic growth phase, stationary phase, and in starved cultures of yeast. PMID- 8482391 TI - Adenine dinucleotide-mediated cytosolic free Ca2+ oscillations in single hepatocytes. AB - Single rat hepatocytes microinjected with aequorin respond to Ca(2+)-mobilizing agonists, including ADP and ATP, with oscillations in cytosolic free Ca2+. We show here that single rat hepatocytes also respond to the adenine dinucleotides Ap3A and Ap4A with Ca2+ oscillations which resemble those induced by ADP and ATP. PMID- 8482392 TI - Exon/intron organization of the gene encoding the mouse epithelin/granulin precursor (acrogranin). AB - Mouse genomic clones encoding the epithelin/granulin gene and its 5'- and 3' flanking regions have been isolated and sequenced. This gene was found to be a single-copy gene, and contained 13 exons interrupted by 12 introns. Eight out of the 12 introns are classified as phase 0, and are located within the central part of each of the tandem repeats in the amino acid sequence of the epithelin/granulin precursor. The first intron is unique because of the interruption of the 5'-untranslated region and its fairly large size (approximately 2.4 kbp). Consensus sequences for several of the potential regulatory elements are present in the 5'-flanking sequence, including a common CCAAT sequence. PMID- 8482393 TI - CoA esters of valproic acid and related metabolites are oxidized in peroxisomes through a pathway distinct from peroxisomal fatty and bile acyl-CoA beta oxidation. AB - In rat liver homogenates fortified with the appropriate cofactors (ATP and CoA), valproic acid induced H2O2 production rates by far lower than those recorded on the straight medium-chain fatty acid n-octanoic acid. Using directly the CoA esters of these carboxylic acids as substrates for the rat liver H2O2-generating enzyme activities, valproyl-CoA, and n-octanoyl-CoA were found to induce similar oxidation rates. In the rat liver homogenates, cyanide-insensitive valproyl-CoA and octanoyl-CoA oxidations occurred at rates similar to those of valproyl-CoA and octanoyl-CoA oxidase(s), respectively. Studies on fractions obtained from rat liver postnuclear supernatants by isopycnic centrifugation on a linear sucrose density gradient disclose that the density distribution of valproyl-CoA oxidase superimposes to those of catalase, fatty acyl-CoA oxidase and cyanide-insensitive fatty acyl-CoA oxidation, three peroxisomal marker activities. By contrast, the cyanide-insensitive valproyl-CoA oxidation does not adopt the typical peroxisomal distribution of these activities but rather exhibits a mitochondrial localization with, however, a minor peroxisomal component. Interestingly enough, the comparative study of rat tissue distribution, inducibility by clofibrate and sensitivity to deoxycholate indicated that valproyl-CoA oxidase is an enzyme distinct from fatty acyl-CoA oxidase and bile acyl-CoA oxidase. Taken as a whole, the results presented here support the occurrence of a peroxisomal oxidation of the CoA ester of valproic acid and its delta 4-enoic derivate which might be characterized by two major features: initiation by an acyl-CoA oxidase distinct from fatty and bile acyl-CoA oxidases, and inability to complete the beta oxidation cycle which would not proceed, at significant rates, further than the beta-hydroxyacyl-CoA dehydrogenation step in peroxisomes. PMID- 8482394 TI - FNA members meet at White House. PMID- 8482395 TI - Are we failing in adolescent health? PMID- 8482397 TI - Ethical issues affecting Florida nurses in clinical practice. PMID- 8482396 TI - Workplace issues. AIDS update. PMID- 8482398 TI - National nurse practitioner leadership summit--1993. PMID- 8482399 TI - How to get sponsored for speaking. PMID- 8482400 TI - Great things happen when agencies unite! PMID- 8482401 TI - Update on public health. PMID- 8482402 TI - Legislative and community response to cocaine use in pregnancy. PMID- 8482403 TI - Nonaccidental injuries in children. PMID- 8482404 TI - Children and violence. PMID- 8482405 TI - Genetic analysis of developmental mechanisms in hydra. XX. Cloning of interstitial stem cells restricted to the sperm differentiation pathway in Hydra magnipapillata. AB - Hydra magnipapillata polyps containing a subpopulation of interstitial stem cells restricted to the germline differentiation pathway were obtained. Chim-C1 is a chimeric strain produced by combining wild-type epithelial cell lineages with a temperature-sensitive interstitial cell lineage. It grows normally at 18 degrees C. When cultured at 25 degrees C, many polyps lost interstitial cells and their differentiation products (nerve cells and nematocytes), and subsequently turned into epithelial hydra unable to move or feed. Some polyps, however, turned into an unexpected type, termed "pseudo-epithelial hydra." These polyps resembled epithelial hydra in the absence of nerve cells or nematocytes in the tissue and in their inability to move or feed. In contrast to epithelial hydra, however, their tissue contained proliferating interstitial cells. Similar pseudo epithelial hydra were also produced from another strain, nem-1, by means of hydroxyurea treatment. Clones of pseudo-epithelial hydra were maintained through force-feeding over 130 days for chim-C1 and over 2 years for nem-1. In both cases, interstitial cells proliferated throughout the period without producing any nerve cells or nematocytes. These interstitial cells, however, differentiated into sperm. Thus, the interstitial cells present in pseudo-epithelial hydra were able to differentiate into gametic cells but not into somatic cells (nerve cells and nematocytes). These observations suggest that, as Littlefield (1985, Dev. Biol. 112, 185-193) has shown for H. oligactis, the interstitial stem cell population in H. magnipapillata includes a subpopulation which can differentiate only into gametic cells. PMID- 8482406 TI - Patterning of heads and feet during regeneration of Hydra oligactis aggregates. AB - The de novo appearance of head organizing centers was monitored during regeneration of aggregates made from dissociated body column tissue of Hydra oligactis using the head-specific monoclonal antibody CP8 (L. C. Javois, R. D. Wood, and H. R. Bode, 1986, Dev. Biol. 117, 607-618). Newly differentiated CP8+ head organizing centers were present by 24 hr of regeneration and were restricted to one half of the aggregate. Depending on subsequent patterning events these CP8+ cells went on to develop into heads or body tentacles, or remained as CP8+ patches. A comparison of the number of initial CP8+ patches with the final number of CP8+ structures indicated that this number was fairly constant, suggesting that a limited number of head organizing centers were established early during regeneration. Examination of fully differentiated head structures revealed that they were segregated to one end of the aggregate with feet segregated away from the CP8+ structures. Increasing the surface area of the aggregates resulted in a more random initial spacing of CP8+ head organizing centers and ultimately a more random distribution of differentiated heads and feet. However, polarized polyps with one head and foot detached and the remaining structures were then segregated. The ability of existing pattern formation models to describe interactions between head- and foot-forming systems resulting in the observed spacing of heads and feet is discussed. PMID- 8482407 TI - Apical orientation of the microtubule organizing center and associated gamma tubulin during the polarization of the retinal pigment epithelium in vivo. AB - Simple epithelial cells express a morphological and functional polarity along their apical-to-basal axis. During the development of epithelia, a unique reorganization of microtubule arrays is thought to play a fundamental role in the establishment of cell polarity. To begin to understand this process in vivo, we have determined the distribution of gamma-tubulin within developing chicken retinal pigment epithelium (RPE). gamma-Tubulin is a recently discovered centrosomal protein that plays a role in nucleating microtubule growth from the centrosome. Although the RPE monolayer becomes established during embryonic Day 3, cell polarity gradually develops and matures over the next 10-13 days. Our studies reveal that gamma-tubulin is located in a distinct focus subjacent to the apical membrane by embryonic Day 3, the beginning of the polarization process. Using primary cell cultures, we examined the relationship between the establishment of junctional complexes and the reorganization of microtubule arrays. Despite the recovery of junctional complexes and a transepithelial electrical resistance, cultured cells failed to relocate gamma-tubulin foci to a position subjacent to the apical membrane. Rather, these foci remained in the juxtanuclear region. These data indicate that the rearrangement of unique, epithelial microtubule arrays requires more than cell-cell and cell-basement membrane interactions. PMID- 8482408 TI - Sources of calcium in sea urchin eggs during the fertilization response. AB - Shortly after sperm-egg interaction the sea urchin egg is traversed by a Ca2+ wave, which is necessary for metabolic activation of the quiescent cell. Several sources including influx across the egg plasma membrane and release from intracellular stores may contribute to the rise in cytoplasmic Ca2+ activity. Inositol 1,4,5-trisphosphate (InsP3), cyclic ADP ribose (cADPR), and ryanodine have been reported to induce intracellular Ca2+ release. We used confocal laser scanning microscopy to image the Ca2+ transient during fertilization and parthenogenetic activation by microinjection of Ca2+ release agonists. A near instantaneous rise in Ca2+ localized to the egg cortex occurred near the time of sperm-egg binding, followed by a distinctive delay before the onset of the Ca2+ wave. Since the rise in cortical Ca2+ activity was absent when Ca2+ influx was prevented, it appeared that this change in Ca2+ activity was due to the opening of membrane Ca2+ channels. Blocking the influx did not alter the onset of the Ca2+ wave. The Ca2+ wave during the fertilization response seemed to require Ca2+ release mediated by InsP3-, cADPR-, and ryanodine-sensitive mechanisms. Parthenogenetic activation by microinjection of these three agents had different spatiotemporal patterns of Ca2+ release. Most significantly the injection of either InsP3 or cADPR, but not ryanodine, induced an enhanced pronucleus associated Ca2+ release, which was similar to the Ca2+ response during fertilization. PMID- 8482409 TI - Changes in expression of nonmuscle myosin heavy chain isoforms during muscle and nonmuscle tissue development. AB - Anti-human platelet myosin antibodies and two anti-peptide antibodies, anti peptide IIA and anti-peptide IIB, which recognize macrophage-type (MIIA) and brain-type (MIIB) isoforms of nonmuscle myosin heavy chain, respectively, were used to study expression of nonmuscle myosin isoforms in various tissues of mice during development. Tissue-specific changes in the relative isoform concentrations were observed by performing immunoblots of crude myosin extracts from nonmuscle and muscle tissues. In fetal and neonatal mouse tissues, the anti peptide IIB antibodies stained a single band, called MIIB2, while the anti peptide IIA and anti-platelet myosin antibodies stained a band that migrated faster than MIIB2. In brain, a slower moving band, MIIB1, started to appear at 2 weeks after birth, and in the adult cerebellum it was at least as abundant as MIIB2. In thymus, MIIB2 decreased selectively shortly after birth, while in liver both MIIB2 and MIIA rapidly disappeared, but the isoform(s) detected by anti platelet myosin antibodies (MIIApla) remained constant. The MIIB2 and MIIA as well as MIIApla found in striated muscles from fetal and neonatal mice decreased to levels that were below the limit of detection by 3 weeks of age. In cryosections of skeletal and cardiac muscles, MIIB2 was localized within the muscle cells, while MIIA and MIIApla were primarily in the blood vessels and capillaries. PMID- 8482410 TI - Cleavage asynchrony in the Tubifex embryo: involvement of cytoplasmic and nucleus associated factors. AB - The smaller AB-cell of the 2-cell embryo of Tubifex divides 40 min later than the larger CD-cell. The present study was undertaken to elucidate those factors that are responsible for this cleavage asynchrony. An examination of chromosome cycles showed that the AB-cell entered M-phase 5 min later and spent about 35 min longer in the prometaphase portion of M-phase than did the CD-cell. Even if cultured in isolation, the length of M-phase of AB isolates continued to be comparable to that of intact AB-cells. When AB and CD nuclei were brought into a common cytoplasm, they entered M-phase simultaneously. The durations of M-phase portions from prometaphase through telophase were not altered even in a common cytoplasm, as long as the mitotic figures of AB and CD nuclei were separated from each other. Only when the mitotic spindles of both nuclei were united at at least one pole was the length of prometaphase of the AB nucleus significantly shortened. Whole-mount immunocytochemistry of microtubules revealed that asters were involved in mitotic spindle assembly in the CD-cell but not in the AB-cell. The fully formed spindle of the AB-cell was anastral and barrel-shaped, while that of the CD-cell possessed asters at its poles. The morphology of the spindle was not altered by changes in the cytoplasmic environments; that is, the spindle of AB nucleus was found to be anastral even in the presence of a CD-cell cytoplasm. These results suggest that unlike the case of other animals so far studied, cleavage asynchrony in the Tubifex embryo is brought about not only by cytoplasmic components but also by nucleus-associated factors. PMID- 8482411 TI - Compartmentalized expression of the alpha- and gamma-subunits of the acetylcholine receptor in recently fused myofibers. AB - The mRNAs encoding the subunits of the acetylcholine receptor are clustered at the level of the neuromuscular junction in adult muscle fibers. We have followed the distribution of the mRNAs encoding the alpha- and gamma-subunits during development of the diaphragm muscle in the mouse by whole-mount in situ hybridization. We show that the mRNAs encoding both subunits display a nonhomogeneous distribution as early as Day 13.5, when the first neuromuscular contacts are formed. Extrajunctional mRNAs disappear during the following days with a concomitant increase in contrast of the synaptic domains. gamma-subunit mRNAs become undetectable at the end of the first postnatal week, together with the appearance of epsilon-subunit mRNAs. Our results imply that the expression of the acetylcholine receptor genes, including the gamma-subunit gene, is compartmentalized soon after neuromuscular contacts have been established. This has important implications for the understanding of the molecular mechanisms of neuromuscular junction formation. PMID- 8482412 TI - Replication timing and Xenopus 5S RNA gene transcription in vitro. AB - The influence of DNA replication in a chromosomal environment on the transcription of Xenopus laevis 5S RNA genes has been examined using low-speed extracts of Xenopus eggs and Xenopus sperm nuclei. The major oocyte- and somatic type 5S RNA multigene families of X. laevis are differentially expressed in these extracts dependent on limiting transcription factors and replicate in different compartments of S-phase. Under these particular experimental conditions the timing of replication of the somatic 5S RNA genes appears to be independent of their transcriptional activity. Moreover, differential transcription of the oocyte- and somatic-type 5S RNA genes is not influenced by the replication process. PMID- 8482413 TI - Multiple kinesin-like transcripts in Xenopus oocytes. AB - Recent evidence shows that kinesin-like proteins (Klps) form a very large multigene family. A recent study using the polymerase chain reaction (PCR) identified six new candidate Klps in Drosophila, making the total number of members of this family in Drosophila at least 11 (Stewart et al., 1991, Proc. Natl. Acad. Sci. USA 88, 4424-4427). The functional basis of this diversity is not clear. Different Klps could have cell type-specific functions, or they could perform different functions within the same cell type, or a mixture of both. To investigate the degree to which different Klps are expressed in the same cell, we chose the Xenopus oocyte. During oocyte differentiation, and in the egg, different types of microtubule-based motility occur; all are important to the normal development of the embryo after fertilization. Using PCR we identified and partially sequenced four novel Klp mRNAs from the Xenopus oocyte (denoted XKlps 1 4). Multialign sequence comparison suggests that one of them, XKlp3, may be the Xenopus counterpart of Drosophila Klp4. Similarly Xenopus Eg5 is closely related to Drosophila Klp2. Northern blot analysis reveals that the Xenopus XKlps have different patterns of expression during embryogenesis. These data show that at least four Klps can exist in the same cell and that they can be differentially regulated during early development, and suggest their differential function in oogenesis and early development. PMID- 8482414 TI - Segment-polarity mutations cause stripes of defects along a leg segment in Drosophila. AB - Various lines of evidence suggest that "segment-polarity" genes, which participate in segmenting the Drosophila embryo, may also play a role in the development of adult structures. Wilkins and Gubb (1991, Dev. Biol. 145, 1-12) have proposed that these genes specify the angular component of the polar coordinate system for each imaginal disc. If true, then segment-polarity mutations should cause abnormal patterning within well-defined sectors of the discs. To test this prediction, a leg segment was used where abnormalities can be precisely identified. The second-leg basitarsus bears eight rows of mechanosensory bristles, plus five chemosensory bristles between specific rows. Abnormalities were sought in the basitarsi of six different segment-polarity mutants and their 15 pairwise compounds. Consistent with the prediction, sectorial defects were indeed found: (1) deletions of specific rows (or chemosensory bristles) or portions thereof and (2) increased bristle number within (or between) specific rows. Both types of abnormalities were associated with changes in the widths of various parts of the circumference, implying that the alterations in bristle patterning may be mediated by regional perturbations of growth. PMID- 8482415 TI - Aberrant expression of Pax-2 in Danforth's short tail (Sd) mice. AB - The pattern of Pax-2 expression was studied in Danforth's short tail homozygous mice using Pax-2-specific antibodies. Because these mice lack a notochord in caudal regions, the floor plate of the spinal cord is not induced and posterior mesoderm-derived structures are also affected. The expression of Pax-2 during neural differentiation in the spinal cord was normal in anterior sections, but ectopic expression in the ventral half of the basal plate was observed in regions lacking the floor plate. The data support the hypothesis that Pax-2 expression domains are influenced by signals emanating from the floor plate and that Pax-2 functions during the dorsal-ventral patterning of the spinal cord. In the developing excretory system, Pax-2 expression was normal in the anterior structures, such as the mesonephros, and in the mesonephric duct. However, Pax-2 was not expressed in the uninduced metanephric mesenchyme. Thus, activation of Pax-2 in the mesenchyme is an early response to inductive signals emanating from the ureter. The Danforth's short tail mutation is a useful model for the study of developmentally regulated genes that are under the influence of the notochord or floor plate. PMID- 8482416 TI - Pronuclear positioning and migration during fertilization in Pelvetia. AB - The position and migration of egg and sperm pronuclei were studied in the brown alga Pelvetia. The egg pronucleus was located near the center of the cell before and after fertilization and, unlike pronuclei in animal eggs, did not migrate. Inhibitor studies indicated that anchoring of the egg pronucleus in the cell center was dependent on microtubules and microfilaments. An extensive array of microtubules, many of which extended into the actin-rich egg cortex, was associated with the egg pronucleus. Migration of the sperm pronucleus was investigated quantitatively in both living and fixed zygotes. Migration occurred linearly at rates from 0.11 to 0.29 microns/min and was oriented directly toward the egg pronucleus in the cell center. Sperm penetration was inhibited by cytochalasin D, which disrupts F-actin function, whereas sperm pronuclear migration was sensitive to the microtubule-depolymerizing drug, nocodazole. Microtubules associated with the migrating sperm pronucleus formed a sperm trail that terminated at the egg cortex. As these were the only microtubules associated with the sperm at early stages of migration, we conclude that they provide the force for migration. PMID- 8482417 TI - Inhibition of precardiac mesoderm cell proliferation by antisense oligodeoxynucleotide complementary to fibroblast growth factor-2 (FGF-2). AB - This laboratory recently reported the occurrence of concentrated deposits of fibroblast growth factor-2 (FGF-2; basic FGF)-like proteins in the sarcoplasm of embryonic cardiac myocytes from the earliest stage of avian heart development (M. H. Parlow, D. L. Bolender, N. P. Kokan-Moore, and J. Lough, Dev. Biol. 146, 139, 1991). To determine the role, if any, of FGF-2 during embryonic cardiogenesis, the proliferative and functional effects of treating cultured anterior lateral plate mesoderm from Hamburger-Hamilton stage 6 embryos with antisense oligodeoxynucleotide (ODN) complementary to FGF-2 mRNA were determined. Within 2 days of culture in defined medium, the explanted monolayer normally differentiates into a multilayer of proliferative cells that express sarcomeric alpha-actin and exhibit rhythmic contractions. The inclusion of 25 microM ODN that is complementary to the second exon of chicken FGF-2 mRNA caused a 50% inhibition in these cells' proliferative ability as judged by incorporation of 5' bromodeoxyuridine; contractility was similarly inhibited. These effects were prevented by including recombinant human FGF-2 protein in the medium. Treatment with sense ODN did not cause inhibition. Inhibition of FGF-2 protein synthesis in the explanted tissue by antisense ODN was verified by immunoprecipitation analysis. These results point to a critical role for FGF-2 in the autocrine regulation of proliferation, and perhaps differentiative function, of embryonic cardiac myocytes. PMID- 8482418 TI - Enhancer regions responsible for temporal and cell-type-specific expression of a spore coat gene in Dictyostelium. AB - The extracellular spore coat of Dictyostelium discoideum is composed of three major proteins, SP96, SP70, and SP60, encoded by the cotA, cotB, and cotC genes, respectively. The spore coat proteins are coordinately synthesized in prespore cells shortly after aggregation, stored in prespore vesicles during the slug stage, and secreted during encapsulation of spores. We have ligated various portions of the upstream region of cotB to lacZ such that a protein consisting of the first nine amino acids of SP70 fused to beta-galactosidase is synthesized in prespore cells. Individual cells that accumulate the enzyme can be observed in situ during early aggregation due to the sensitivity of the assay. We have found that prespore cells first appear in a random distribution throughout the aggregates with no indication of spatial localization. They subsequently sort out from prestalk cells that form a tip on the aggregates. The cotB regulatory region was subdivided into a proximal and a distal region, each of which could independently direct proper temporal and cell-type control. Transcriptional activity directed by these two regions appears to be additive in the full-length regulatory region. The proximal region was shown to be complex in that removal of certain portions partially reduced transcriptional activity while removal of other portions abolished all activity. Nevertheless, cells transformed with constructs showing attenuated activity expressed the fusion gene at the proper time in development and the activity was localized to prespore cells. The cis acting regions responsible for all aspects of cotB regulation appear to be closely opposed within the minimal essential sequence of the proximal region. PMID- 8482419 TI - PS2 integrin requirements in Drosophila embryo and wing morphogenesis. AB - The Drosophila inflated (if) gene encodes the alpha PS2 subunit of the PS integrins. We describe the generation of new if mutations, their lethal embryonic phenotype, and experiments that examine the spatial and temporal requirements for integrins in adult wing morphogenesis. Embryos hemizygous for either new allele, ifA7 or ifB2, make reduced amounts of alpha PS2. In a variety of genetic tests, these alleles behave similarly to ifk27e, which makes no detectable alpha PS2, and all three alleles display the same embryonic phenotype. We therefore conclude that all of the lethal alleles retain little or no wild-type alpha PS2 function. As seen for strong mutations at the myospheroid (mys) locus, which encodes the beta PS integrin subunit, if mutants show extreme defects in somatic muscle attachments and in midgut morphogenesis. Unlike mys, however, there is no dorsal herniation of the if mutant embryos. With respect to wing morphogenesis, clonal analysis experiments demonstrate that if+ function is required only in cells of the ventral wing surface. We have rescued the wing blister phenotype of double mutants for the hypomorphic mysnj42 and if3 alleles using a heat shock-inducible mys+ transgene. By varying times of transgene induction, we find that integrin function is required from very early in metamorphosis until at least the last 24 48 hr of wing development. PMID- 8482420 TI - A subtle defect underlies altered lamellar orientation in the Gr16 chorion mutant of Bombyx mori. AB - Gr16 (chromosome 2, 6.9 cM) is a dominant, grey egg mutation of the domestic silkmoth, Bombyx mori, which produces an opaque instead of a translucent chorion. To determine the underlying cause of this defect, we examined the effects of the mutation on chorion ultrastructure, protein accumulation, and biosynthesis patterns, and on the restriction patterns of early chorion structural genes, using the presumed wild-type progenitor strain, Old European 16 (OE16), for comparison. Cross-sections of mature chorions examined by scanning electron microscopy showed that the inner lamellae were oriented perpendicular, rather than parallel, to the egg surface, with a smaller vertical zone bordered by normally oriented lamellae in the heterozygote, suggestive of codominant expression. This defect first appeared in transmission electron micrographs early in choriogenesis, probably during framework formation and/or expansion stages. Mature chorion protein patterns resolved by isoelectric focusing or two dimensional polyacrylamide gel electrophoresis, synthetic profiles of virtually all chorion proteins following pulse-labeling with tritiated or [14C]glycine, and restriction patterns of early chorion genes examined by Southern blot hybridization were identical between mutant, wild-type, and heterozygote. These observations ruled out a major deletion of chorion structural genes or defects in the production and accumulation of normal chorion proteins as mechanisms underlying the mutation, unlike other putative Gr mutants mapping in its vicinity. The sole difference that we detected was a set of minor, early protein doublets of related size but differing isoelectric point, which showed reciprocal labeling intensities in Gr16 vs OE16 and were codominantly expressed. Preliminary pulse-chase experiments suggested that these proteins may be post-translationally modified forms which undergo differential processing in mutant and wild-type. Based on these observations, we postulate that the Gr16 mutation affects the primary structure of a minor, previously unidentified chorion or follicular cell component which is critical for determining lamellar orientation, and discuss models of how this might function. PMID- 8482421 TI - The winds of change. PMID- 8482422 TI - Tumor necrosis factor-alpha prevents rejection of islet xenografts (rat to mouse). AB - The effect of in vivo administration of exogenous tumor necrosis factor-alpha on the survival of rat islet xenografts in STZ-induced diabetic mice was examined. Daily subcutaneous injections of purified recombinant murine TNF-alpha (3 micrograms/day) for 7 days after transplantation of islets prolonged the survival of the xenografts (26.7 +/- 4.9 days) compared with controls (11.2 +/- 1.1 days). Extension of the treatment from 0 to 59 days after transplantation produced an even greater prolongation of graft survival (53.7 +/- 8.5 days). After cessation of treatment, an accelerated rejection of the grafts occurred. A most interesting finding was that delaying initiation of treatment until 3 days after transplantation and continuing until 60 days produced a remarkable prolongation of xenograft survival (mean survival time > 89.8 +/- 17.5 days) with 2 recipients still normoglycemic at 124 days. Removal of the grafts at this time returned the 2 mice to a diabetic state. A second islet transplant from the same donor rat strain (Wistar-Furth) had an accelerated rejection, indicating that the long-term survival of the xenografts was not because of induction of tolerance. Delaying initiation of TNF treatment until 6 days after transplantation produced only a slight prolongation of survival (17.5 +/- 1.2 days). Prolongation of islet xenograft survival also was obtained by continuous, subcutaneous delivery of TNF alpha by a 7-day mini-osmotic pump (3 micrograms/day). Lower daily doses of TNF alpha (0.003, 0.3, and 1.0 micrograms) had no effect on graft survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482423 TI - Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. AB - The biological effects and the metabolism of the intestinal hormone glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 were studied in normal healthy subjects. GLP-1 7-36 amide and GLP-1 7-37 equipotently stimulated insulin secretion (integrated hormone response 0-60 min, 631 +/- 211 vs. 483 +/- 177 pmol/h x L-1) and C-peptide secretion (integrated hormone response 9064 +/- 1804 vs. 9954 +/- 2031 pmol/h x L-1) and equipotently lowered plasma glucose (integrated decrease 48.3 +/- 5.7 vs. 46.2 +/- 8.4 mmol/h x L-1) and plasma glucagon (integrated decrease 80.4 +/- 24.3 vs. 156.0 +/- 34.6 pmol/h x L-1). Both GLP-1 7-36 amide and GLP-1 7-37 lowered the plasma concentration of free fatty acids significantly. The plasma half-lives of GLP-1 7-36 amide and GLP-1 7 37 were 5.3 +/- 0.4 vs. 6.1 +/- 0.8 min, and the metabolic clearance rates of the two peptides also were similar (14.6 +/- 2.4 vs. 12.2 +/- 1.0 pmol/kg x min). In conclusion, COOH-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas. PMID- 8482424 TI - Glucose-induced amplitude regulation of pulsatile insulin secretion from individual pancreatic islets. AB - The insulin secretory response to glucose was studied in single pancreatic islets isolated from ob/ob mice and rats. The perfusate from an individual islet was collected during 18-s periods and analyzed for insulin with an ELISA technique. Increase of the glucose concentration from 3 to > or = 5.5 mM resulted in pulses of insulin release often originating from the basal level and having a frequency of 0.4/min. Glucose regulation of insulin release from the individual islet was manifested by alterations of the amplitudes of the pulses but not of their frequency. It is concluded that the large amplitude oscillations of cytoplasmic Ca2+ known to occur in the pancreatic beta-cells have their counterpart in pulses of insulin release and that glucose stimulation of the secretory activity may be the result of recruitment of more beta-cells into an oscillatory state. PMID- 8482425 TI - Physical training reverses defect in mitochondrial energy production in heart of chronically diabetic rats. AB - This study examined the impact of physical training on cardiac mitochondrial respiration of rats with chronic diabetes mellitus. Diabetes was induced by an intravenous injection of STZ (50 mg/kg) and only rats with a blood glucose level between 14 and 22 mM 1 wk later were kept in the protocol. Exercise training was conducted on a treadmill with a progressive 10-wk program. Animals were killed at the end of the training program, and mitochondria were isolated from ventricular tissue by differential centrifugation. Both state 3 respiration and oxidative phosphorylation rates were depressed significantly in the mitochondria of diabetic rats. These alterations were reversed completely to normal by physical training, without any significant changes in plasma glucose or insulin levels. The activity of ANT was not affected by diabetes or training. These results indicate that the depressed OPR present in isolated heart mitochondria from chronically diabetic rats is reversed to normal by physical training, apparently by mechanisms independent of blood glucose control. This correction in mitochondrial energy production may explain the improvement in cardiac function previously reported in trained diabetic rats. PMID- 8482426 TI - Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. AB - Extreme insulin resistance occurs in patients with primary defects in insulin action at the receptor or postreceptor levels. The condition commonly is associated with acanthosis nigricans and ovarian masculinization. Despite a marked increase in insulin secretion, some patients develop frank diabetes mellitus that does not respond adequately to insulin therapy. Insulinlike growth factor I exerts metabolic effects similar to those of insulin. This study assessed the potential effectiveness of IGF-I as a blood glucose lowering agent in patients with extreme insulin resistance syndromes, including type A insulin resistance, congenital generalized lipodystrophy, and leprechaunism. Among the 11 patients studied, some exhibited mutated insulin receptors, whereas others were suspected to have defects in postreceptor sites. In each patient, plasma glucose levels decreased in response to subcutaneous injections of recombinant human IGF I (0.1-0.3 mg/kg body wt). The degree of the decrease was roughly comparable with that observed in normal individuals. IGF-I also reduced plasma insulin concentrations. A long-term trial of IGF-I (up to 16 mo) showed that IGF-I (0.1 0.4 mg/kg body wt twice daily) is effective in lowering both fasting and postprandial plasma glucose concentrations with decreases in both fructosamine and HbA1c values. Improvement of acanthosis nigricans was observed in some of the patients. These results suggest that recombinant human IGF-I could be used clinically as a hypoglycemic agent in diabetic patients with extreme insulin resistance in whom insulin treatment is ineffective. PMID- 8482427 TI - Predicting diabetes. Moving beyond impaired glucose tolerance. AB - We developed predictive models for type II diabetes using stepwise multiple logistic regression analyses of a cohort of 844 Mexican Americans and 641 non Hispanic whites who were nondiabetic at baseline and who were then followed for 8 yr. Models were developed for the overall population and separately for each sex and ethnic group. For optimal models, the multiple logistic regression program selected potential risk factors from a panel of 5 categorical and 14 continuous demographic, anthropometric, metabolic, and hemodynamic variables. For reduced models, the list of candidate variables was restricted to those commonly used in ordinary clinical practice, i.e., skinfolds, and serum insulin and postural glucose load variables were excluded. For all models, the stepwise process selected a mixture of anthropometric, glucose, lipid, and hemodynamic variables. The top 15% of the risk continuum for each model was defined as high risk to compare the performance of the models with the performance of impaired glucose tolerance (15% prevalence) as a predictor of diabetes. The relative risk of being high risk ranged from 12.16 to 35.29, whereas the relative risk of having impaired glucose tolerance ranged from 7.11 to 10.0. The sensitivity of the multiple logistic regression models ranged from 67.7 to 83.3% compared with 56.5 to 62.1% for impaired glucose tolerance. The results indicate that multivariate predictive models perform at least as well, if not better than impaired glucose tolerance in predicting type II diabetes but need not require an oral glucose load. Moreover, the models highlight the complex metabolic and hemodynamic syndrome that precedes diabetes. PMID- 8482428 TI - Impact of arterial blood pressure and albuminuria on the progression of diabetic nephropathy in IDDM patients. AB - To evaluate the impact of systemic blood pressure and albuminuria on the progression of diabetic nephropathy, we followed 41 IDDM patients with persistent albuminuria (> 300 mg/24 h) by measuring glomerular filtration rate (51Cr-EDTA technique), blood pressure, and albuminuria. None of the patients were taking drugs other than insulin. Arterial blood pressure, albuminuria, and blood glucose were measured four to eight times/yr, whereas glomerular filtration rate was determined twice yearly. During the median investigation period of 36 (15-66) mo, glomerular filtration rate decreased from 102 +/- 23 to 83 +/- 27 ml.min-1 x 1.73 m-2 (P < 0.001), albuminuria increased from 633 to 1435 micrograms/min (P < 0.001), and blood pressure rose from 133/85 +/- 10/9 to 149/93 +/- 8/11 mmHg (P < 0.001). Univariate analysis revealed a significant correlation between the rates of decline in glomerular filtration rate and diastolic blood pressure (r = 0.52, P < 0.01) and glomerular filtration rate and albuminuria (r = 0.34, P < 0.02). But stepwise multiple linear regression analysis only showed a significant correlation between the rate of decline in glomerular filtration rate and diastolic blood pressure (P < 0.01). In patients with diastolic blood pressure below the mean value of 89 mmHg, stepwise multiple regression analysis showed that albuminuria and not blood pressure was correlated significantly with rate of decline in glomerular filtration rate. Patients were stratified by average value of diastolic blood pressure measured during the investigation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482429 TI - Thoracic duct lymph. Relative contribution from splanchnic and muscle tissue. AB - We have shown previously that thoracic duct lymph insulin dynamics are well correlated with tracer-determined whole-body glucose uptake and have suggested that thoracic duct lymph insulin is representative of insulin concentration in muscle interstitial fluid. However, thoracic duct lymph is comprised of interstitial fluid from all sub-thoracic tissue beds. To investigate the relative contribution of muscle interstitial fluid to total thoracic duct lymph flow, the distribution and elimination of [14C]inulin was investigated in eight experiments with conscious dogs. Both plasma and thoracic duct lymph were measured, and a three-compartment model that was hypothesized to consist of plasma, splanchnic interstitial fluid, and muscle interstitial fluid was identified. Identifications were performed with either a bolus protocol (n = 4) or an infusion protocol (n = 4), and the predicted [14C]inulin dynamics in the splanchnic and muscle interstitial fluid compartments were compared with measured values in thoracic duct lymph. Neither compartment predicted the thoracic duct [14C]inulin dynamics; however, a model based on a percentage contribution from each tissue bed fit the thoracic data well. The relative contribution of splanchnic interstitial fluid to the total thoracic duct lymph flow averaged 78 +/- 5% for the bolus protocol and 54 +/- 5% for the infusion protocol. Thus, we conclude that in the conscious animal, approximately 25-50% of thoracic duct lymph originates from muscle interstitial fluid. PMID- 8482430 TI - Limitations in the use of [2-14C]acetate for measuring gluconeogenesis in vivo. AB - This study was undertaken to test two assumptions critical for use of [2 14C]acetate to measure gluconeogenesis in vivo. For the assumption that incorporation into glucose of products of [14C]acetate metabolism does not affect the distribution of label within the glucose molecule, we infused [2-14C]acetate in 17 healthy subjects and [3-14C]lactate in 10 healthy subjects and compared the ratio of the resultant specific activities of plasma glucose carbons 1, 2, 5, 6, and 3, 4 obtained with each tracer. The ratio obtained with [2-14C]acetate (2.99 +/- 0.07) was significantly different from the ratio obtained with [3 14C]lactate, (3.82 +/- 0.2, P < 0.01). Because the model predicts that these ratios should be identical, these results indicate that either the model is incorrect or that metabolism of [14C]acetate to other compounds affects the distribution of the label within the glucose molecule. To test the assumption that plasma 3-OH-butyrate specific activity approximates the specific activity of hepatic intramitochondrial acetyl CoA, we compared the ratio of specific activities of plasma glucose and 3-OH-butyrate obtained in 7 healthy subjects infused with [2-14C]acetate and [2-14C]octanoate. The ratio obtained with [2 14C]acetate (0.18 +/- 0.03) was significantly different from that obtained with [2-14C]octanoate, (0.10 +/- 0.02), P < 0.001. These results suggest compartmentalization of acetyl CoA within liver mitochondria and indicate that plasma 3-OH-butyrate specific activity may not necessarily approximate intramitochondrial acetyl CoA specific activity during [2-14C]acetate infusion. We conclude that assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo are not valid. PMID- 8482431 TI - Genotoxic agents increase expression of growth arrest and DNA damage--inducible genes gadd 153 and gadd 45 in rat pancreatic islets. AB - Pancreatic beta-cells are able to repair themselves after some sublethal injuries in vitro. However, little is known of the nature of the repair mechanisms active in these cells. This study examined the expression of growth arrest and DNA damage--inducible genes gadd 153 and gadd 45 in pancreatic rat islets and in the clonal insulin secretory HIT-T15 cells. Rat pancreatic islets were exposed in vitro to the alkylating agents streptozocin or methyl methanesulfonate, or to the cytokine recombinant interleukin-1 beta. Islet exposure to STZ or MMS reduced insulin release by 40-50% over the next 4 h, whereas exposure to rIL-1 beta induced a 60% increase in insulin release over the same period. Both gadd 153 and gadd 45 mRNA were detectable in rat islets, and their levels were increased twofold after STZ exposure, whereas MMS induced a fivefold increase in gadd 153 and a twofold increase in gadd 45 mRNA. Islet exposure to rIL-1 beta did not affect the expression of gadd 153 or gadd 45. HIT cells exposed to STZ or MMS also exhibited an increased expression of both gadd 153 and gadd 45. Again, this increase in gadd mRNA was more marked after MMS exposure. Moreover, expression of both gadd 153 and gadd 45 after MMS exposure lasted for a longer period of time than after STZ treatment. The effects of MMS on the expression of both gadd genes were inhibited by actinomycin D, suggesting that transcription is necessary for acute gadd induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482432 TI - Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocrine pancreas. AB - The actions of transforming growth factor-beta isoforms as potent regulators of growth and differentiation have led to the examination of their presence in the human pancreas. The cellular localization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 was assessed in the normal human pancreas by using immunohistochemical and in situ hybridization techniques. Although cytoplasmic immunoreactivity for TGF-beta 1, TGF-beta 2, and TGF-beta 3 was found in islet cells, acinar cells, and ductal cells, a differential immunostaining pattern for TGF-beta isoforms was observed. In the endocrine pancreas, the islet cells demonstrated diffuse cytoplasmic immunostaining for TGF-beta 1, TGF-beta 2, and TGF-beta 3. However, only TGF-beta 2 and TGF-beta 3 exhibited an intense pattern of immunostaining in a few endocrine cells. Most of the positive islet cells coexpressed insulin. In contrast, in the exocrine pancreas, a greater number of acinar cells showed immunoreactivity for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3. In the ductal cells, all three TGF-beta isoforms showed a similar intensity and pattern of immunostaining and were observed more frequently in the smaller distal ductules than in the larger pancreatic ducts. TGF-beta 1 and TGF-beta 3, but not TGF-beta 2, immunostaining was detected strongly in the smooth muscle cells and weakly in the endothelial cells of the blood vessels, whereas the fibroblasts of the interstitium were completely negative. In situ hybridization revealed that mRNA encoding all three TGF-beta isoforms colocalized with their respective proteins in islets, acinar cells, and ductal cells. In contrast, mRNA expression was absent in the smooth muscle cells and endothelium of the vessels. These results suggest that TGF-beta isoforms may act by both autocrine and paracrine mechanisms in the pancreas. The differential pattern of expression observed for each TGF beta isoform implies unique roles for these proteins in the regulation of the endocrine and exocrine pancreas. PMID- 8482433 TI - Fasting does not impair insulin-stimulated glucose uptake but alters intracellular glucose metabolism in conscious rats. AB - Effects of 24-h and 48-h fasting on maximal insulin-stimulated whole-body and muscle glucose uptake, glycogen synthesis, and glycolysis were studied in conscious rats by combining the glucose clamp technique with tracer methods. Fasting decreased body weight and basal plasma glucose, plasma insulin, hepatic glucose output, and glucose clearance (P < 0.05 for all). However, maximal insulin-stimulated whole-body glucose uptake, normalized to body weight, was almost identical in fed, 24-h fasted, and 48-h fasted rats (191 +/- 8, 185 +/- 14, and 182 +/- 5 mumol.kg-1.min-1, respectively; P > 0.7). Similarly, rates of insulin-stimulated glucose uptake by four different skeletal muscles, estimated by the 2-deoxyglucose injection technique, were not different among the three groups. In contrast to glucose uptake, insulin-stimulated whole-body glycolysis was decreased significantly after fasting (36% after 48 h fasting; P < 0.05), whereas insulin-stimulated whole-body glycogen synthesis was increased (44% after 48 h fasting; P < 0.05). In fed rats, glycolysis was the major pathway for glucose metabolism during hyperinsulinemia, accounting for 60 +/- 5% of glucose uptake. This fraction was decreased significantly by fasting (P < 0.01), so that after a 48-h fast, glycolysis accounted for only 40 +/- 3% of insulin-stimulated glucose uptake and glycogen synthesis became predominant pathway, accounting for 60 +/- 3% of whole-body glucose utilization. Whole-body patterns of glucose metabolism during hyperinsulinemia were paralleled by glucose metabolism in individual muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482434 TI - In vivo glucose metabolism in obese and type II diabetic subjects with or without hypertension. AB - This study examined whether the presence of hypertension, an insulin-resistant condition, exacerbates the defect in insulin action observed in obesity and type II diabetes mellitus. Glucose metabolism in the basal state and in response to insulin was quantitated by using the euglycemic insulin (20 mU.min-1 x m-2) clamp in combination with 3-[3H]glucose infusion and indirect calorimetry in 20 obese nondiabetic subjects (10 hypertensive and 10 normotensive), 26 type II diabetic subjects (13 hypertensive and 13 normotensive), and 11 normal nondiabetic subjects. The two groups of obese subjects and the two groups of diabetic subjects were matched for sex, age, race, body mass index, and fat distribution. Both in the basal state and during insulin infusion, glucose disposal rates (total, oxidative, and nonoxidative) were similar in obese subjects with or without hypertension. Compared with control subjects, both groups of obese subjects were markedly insulin resistant. Similarly, type II diabetic individuals, whether normotensive or hypertensive, were equally insulin resistant. The severity of insulin resistance was nearly identical in obese and diabetic groups. In diabetic subjects, the inhibitory effect of insulin on hepatic glucose output, lipolysis, and lipid oxidation was blunted compared with normal subjects. In obese subjects the ability of insulin to inhibit lipolysis and lipid oxidation was impaired. However, hypertension did not alter the suppressive effects of insulin on hepatic glucose production, plasma free fatty acid levels, or lipid oxidation in either obese or type II diabetic subjects. These results indicate that hypertension does not confer a greater severity of insulin resistance than that already is present in obesity and type II diabetes mellitus. PMID- 8482435 TI - Organization of the human GLUT2 (pancreatic beta-cell and hepatocyte) glucose transporter gene. AB - The gene encoding the predominant facilitative glucose transporter expressed in pancreatic beta-cells and hepatocytes, termed GLUT2, has been cloned and characterized. The human GLUT2 gene is composed of 11 exons spanning approximately 30 kilobases. The sequence of the promoter region and all exons and adjacent intron regions has been determined and deposited in the GenBank database. Two highly polymorphic simple tandem repeat DNA polymorphisms useful for linkage studies were localized in introns 1 and 4a. In addition, a 168-base pair insertion/deletion polymorphism was identified in intron 3. The characterization of the human GLUT2 gene will facilitate studies of its role in the development of diabetes mellitus. PMID- 8482436 TI - Banting Lecture. On the honey disease. A dialogue with Socrates. PMID- 8482437 TI - Proopiomelanocortin gene expression as a neural marker during the embryonic development of Xenopus laevis. AB - Proopomelanocortin (POMC) is the precursor protein for a number of peptide hormones and neuropeptides, and the POMC gene is transcriptionally very active in the pars intermedia of the pituitary of the amphibian Xenopus laevis (Xenopus). We analysed the expression of this gene during Xenopus embryogenesis, in order to examine whether it can function as a (novel) neural marker. We investigated the spatio-temporal distribution of POMC mRNA, using a single-stranded probe that corresponds to the 3' untranslated region of Xenopus POMC gene B mRNA. Gene transcripts were first detected at stage 25 of development via RNase protection assays. In situ hybridization analysis performed at stage 46 showed clearly that these transcripts are localised in a region representing the future pars intermedia of the pituitary. Experiments using Xenopus explants indicate that the POMC gene can be used successfully as an indirect marker in studies on neural induction: in the absence of interactions with mesoderm, ectoderm fails to express the POMC gene, whereas POMC transcripts are readily detectable in conjugates of ectoderm and mesoderm. Artificial application of two different signals, which are likely to be relevant for neural differentiation (namely retinoic acid and the activation of protein kinase C via phorbol ester), was not effective in evoking POMC gene expression in cultured ectoderm explants. However, retinoic acid treatment of conjugates of Xenopus ectoderm and mesoderm successfully prevented POMC expression. We conclude that POMC gene expression can be used as an indirect marker for anterior neural differentiation in Xenopus. PMID- 8482438 TI - Altered morphogenesis of the immature hamster uterus following neonatal exposure to diethylstilbestrol. AB - In previous studies, we found that a single neonatal exposure to diethylstilbestrol (DES) resulted in severe hyperplasia and a high incidence of endometrial adenocarcinoma in the uterus of adult hamsters. These observations prompted us to investigate the consequences of DES exposure on earlier stages of uterine morphogenesis. After neonates were treated within 6 h of birth (day 1) with 100 micrograms of DES or oil vehicle, uterine tissue morphometry plus cell labelling indices following in vivo pulse labeling with [3H]thymidine were determined on days 3-21 of life. The sequential findings were: (1) a precocious (day 3) burst of cellular proliferation throughout the uterus, (2) an early period (days 3-9) of hypertrophy and increased cell density in the luminal epithelium, (3) an extreme acceleration of uterine growth resulting in a persistent increase in total uterine mass (> threefold enhancement on days 5-21), (4) precocious development of endometrial glands (day 9) that were sites of intense but transient proliferative activity, (5) a middle period (days 9-15) when the percentage of stromal cells engaged in proliferative activity was reduced, (6) a second wave (days 15-21) of enhanced proliferative activity in the luminal epithelium, and (7) later development (day 21) of reduced cell density in the uterine stroma, apparently due to increased intercellular collagen accumulation. These results support our working hypothesis that the acute uterotropic response to neonatal DES treatment initiates a change in the developing hamster uterus, and later estrogenic stimulation promotes neoplastic progression in the DES-altered adult organ, perhaps due to disruption of stromal epithelial interactions. PMID- 8482439 TI - A short, eclectic history of exocrine pancreatic insufficiency and chronic pancreatitis. PMID- 8482440 TI - Intestinal antibody pattern of celiac disease: occurrence in patients with normal jejunal biopsy histology. AB - BACKGROUND: Patients with celiac disease have immunoglobulin (Ig) M antibodies and IgA antigliadin antibody in gut secretions; this pattern of intestinal immunity may be a marker of latent celiac disease. Its frequency in patients referred for jejunal biopsy has been examined. METHODS: Serum IgG and IgA antigliadin antibody, jejunal fluid IgA and IgM antibodies to gliadin, ovalbumin and beta lactoglobulin, and jejunal fluid IgA and IgM concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Seventeen of 19 celiac patients on normal diet and 16 of 23 on gluten-free diet had the celiaclike antibody pattern, as did 41 of 217 other patients. Jejunal biopsy histology had been classified as normal in 38 of these, with minor abnormalities in 3; however, intraepithelial lymphocyte (IEL) counts were high in 13 cases. Trial of a gluten free diet produced clinical improvement in 6 of 7 antibody-positive patients. After extra dietary gluten, one developed subtotal villous atrophy. CONCLUSIONS: The celiaclike intestinal antibody pattern and a high IEL count may be markers of latent gluten-sensitive enteropathy; some of these patients are clinically gluten sensitive in the absence of enteropathy. PMID- 8482441 TI - Accuracy of cutaneous recordings of gastric electrical activity. AB - BACKGROUND: This study was undertaken to determine the accuracy of cutaneous electrogastrography (EGG). METHODS: The ability of EGG to assess gastric contractions and electrical frequency, phase lag, and waveform was studied in 4 healthy volunteers with cutaneous electrodes before and after eating, 4 healthy fasting volunteers with intraluminal pressure recording tubes and cutaneous electrodes, 1 patient with surgically implanted gastric serosal electrodes, and 4 anesthetized dogs with serosal force transducers and implanted and cutaneous electrodes. In 2 of the dogs, an intragastric distending balloon was introduced. RESULTS: The use of long-distance serosal electrodes allowed direct comparison of internal and cutaneous signals. Cutaneous electrodes recognized 80%-85% of changes in frequency with spectral analysis. Only 30%-40% of increases in EGG amplitudes were associated with gastric contractions. Gradual distention of the canine stomach after blocking contractions with atropine and glucagon increased the EGG amplitudes. No appreciable phase lag could be discerned with EGG. The descending portion of the EGG waveform was predominant. CONCLUSIONS: Frequency dynamics is currently the only reliable cutaneous EGG parameter. PMID- 8482442 TI - Nonspecific motor disorder of the esophagus: a real disorder or a manometric curiosity? AB - BACKGROUND: Nonspecific esophageal motility disorder (NEMD) has become a catchall term to describe abnormal esophageal manometric findings that do not meet strict criteria for established esophageal motility disorders. The aim of this study was to determine whether NEMD is a real esophageal motility disorder characterized by impairment of its motor function or simply a manometric disturbance with no clinical consequences. METHODS: Esophageal transit of liquid and semisolids was studied using radioscintigraphic techniques in 10 symptomatic patients with manometrically diagnosed NEMD, 26 healthy control subjects, and 40 disease control subjects. The disease controls included 24 patients with achalasia, 9 with scleroderma, and 7 with diffuse esophageal spasm. RESULTS: Patients with NEMD had no impairment of liquid emptying compared with healthy controls. Liquid emptying was markedly delayed in patients with achalasia and scleroderma. However, semisolid emptying was markedly delayed in patients with NEMD compared with healthy controls (P < 0.001), and the extent of its delayed emptying was similar to that seen in patients with achalasia, scleroderma, and diffuse esophageal spasm. CONCLUSIONS: NEMD is not a manometric curiosity but a disorder characterized by selective impairment of semisolid emptying. PMID- 8482443 TI - Mesalamine capsules for the treatment of active Crohn's disease: results of a 16 week trial. Pentasa Crohn's Disease Study Group. AB - BACKGROUND: Mesalamine is released from sulfasalazine in the colon and benefits colonic Crohn's disease. The mesalamine used in this study releases the drug throughout the small bowel and colon. Therefore, this study was designed to detect benefit for Crohn's disease involving the small bowel alone or both the colon and small bowel. METHODS: This double-blind, randomized, multicenter prospective controlled trial compared placebo and three daily doses of mesalamine in 310 patients. The primary outcome criterion was change in the Crohn's Disease Activity Index (CDAI) from baseline to final study visit. RESULTS: Patients taking 4 g/day mesalamine experienced a decrease of 72 CDAI points compared with 21 points in the placebo group (P < 0.01). Remission occurred in 43% of the 4-g group and 18% of the placebo group. Patients with ileum-only disease showed a 93 point improvement on 4 g mesalamine, compared with a 2-point improvement in similar patients on placebo. Mesalamine in this trial was not associated with clinically significant toxicity. CONCLUSIONS: This controlled-release mesalamine preparation is safe and effective at 4 g/day as a single agent in treatment of active Crohn's disease of the ileum and colon. PMID- 8482444 TI - A novel human macrophage-derived intestinal mucin secretagogue: implications for the pathogenesis of inflammatory bowel disease. AB - BACKGROUND: A novel 68-kilodalton macrophage-derived protein (MMS-68) stimulating mucin release from respiratory epithelial cells has previously been described. In this study, the effect of MMS-68 on mucin release from intestinal epithelial cells was determined. METHODS: Colonic epithelial cells isolated from normal colon, ulcerative colitis, Crohn's colitis, and cells from three colon cancer cell lines were labeled with [3H]-glucosamine and stimulated with MMS-68. High molecular weight glycoproteins were precipitated and counted. RESULTS: In all of the cells tested, MMS-68 enhanced mucin secretion by 1.46-2.0-fold above control values, comparable to the level achieved with carbachol (10(-5) mol/L). Coincubation with anti-MMS-68 monoclonal antibody 1D-10 blocked this bioactivity. Freshly isolated intestinal macrophages reacted with monoclonal antibody 1D-10. Immunofluorescent staining of frozen sections revealed the presence of MMS-68 producing cells (macrophages) in the lamina propria of normal colon and Crohn's colitis, with weaker expression in ulcerative colitis mucosa. CONCLUSIONS: Intestinal macrophages produce a novel mucin secretagogue, which is as potent as carbachol for stimulating mucin secretion from colonic epithelial cells. This factor may explain, in part, the alterations in mucin secretion often seen in inflammatory bowel disease. PMID- 8482445 TI - Menetrier's disease: a form of hypertrophic gastropathy or gastritis? AB - BACKGROUND: Menetrier's disease is characterized by giant gastric folds and foveolar hyperplasia. The extent of mucosal inflammation and glandular atrophy, however, is controversial. The aim of this study was to test the hypothesis that patients previously diagnosed with Menetrier's disease actually represent at least two diseases: (1) Hypertrophic lymphocytic gastritis (HLG) and (2) Massive foveolar hyperplasia and minimal inflammation (MFH). METHODS: All cases of possible Menetrier's disease were identified, and their clinical, laboratory, and pathological data were reviewed. In twenty-three patients with giant fundal folds, full-thickness tissue specimens (n = 19) or large suction biopsy (n = 4) tissue specimens were obtained. RESULTS: Two distinct, nonoverlapping histological patterns were found; 13 patients had HLG and 10 patients had MFH. Clinical features and frequency of Helicobacter pylori were similar in these two groups. Patients with HLG had severe inflammation with numerous intraepithelial lymphocytes and mild foveolar hyperplasia. Alternatively, patients with MFH had greater foveolar hyperplasia, significantly thicker mucosa, and greater mucosal edema. CONCLUSIONS: Patients with MFH represent a form of hypertrophic gastropathy and should be designated as having Menetrier's disease, whereas patients with HLG should be considered part of the spectrum of lymphocytic gastritis. PMID- 8482446 TI - Mechanism of gastroprokinetic effect of EM523, an erythromycin derivative, in dogs. AB - BACKGROUND: The pharmacological properties of EM523, a nonpeptide motilin agonist, have not been well characterized. METHODS: The prokinetic effect of EM523 on motor-stimulating activity in the stomach, duodenum, and jejunum in seventeen conscious dogs was studied using force transducers implanted long term. EM523 (0.3-10.0 micrograms/kg) and receptor antagonists were injected intravenously during the interdigestive state. RESULTS: EM523 induced phase III like contractions in a dose-dependent manner, and the contractions were inhibited dose dependently by pretreatment with cholinergic and 5-HT3 receptor antagonists and dopamine but not by adrenoceptor and opiate antagonists or methysergide. The plasma immunoreactive motilin level was increased after EM523 to 60% of the mean maximum value during the spontaneous phase III contractions. Pretreatment with anti-canine motilin serum inhibited EM523-induced contractions by 19.2% in the motor index, but the contractile pattern was not affected. CONCLUSIONS: EM-523 induced phase III-like contractions are brought about through the cholinergic neural pathway and 5-HT3 receptors, and endogenous motilin release is partially involved. PMID- 8482447 TI - Effect of endothelin 1 on ion transport in isolated rat colon. AB - BACKGROUND: Endothelin may play a significant role in the regulation of gastrointestinal function because it has a variety of biological activities and because endothelin-like immunoreactivity as well as its specific binding sites have been found in the gastrointestinal tract. This study investigated the secretory effect and mechanism of action of endothelin 1 in mammalian large intestine. METHODS: Distal colonic segments from Sprague-Dawley rats were stripped of their muscle layers and mounted in Ussing chambers. The effects of endothelin 1 on short-circuit current in rat colonic mucosa were studied in the absence or presence of specific inhibitors. Transmural unidirectional 22Na+ and 36Cl- fluxes and endothelin 1-induced prostacyclin release were also measured. RESULTS: Serosal addition of endothelin 1 evoked a sustained increase in short circuit current that was significantly reduced by tetrodotoxin or atropine, and virtually abolished by a selective endothelin A receptor antagonist (BQ-123), furosemide, piroxicam, d,I-verapamil, or removal of serosal calcium. Hexamethonium, amiloride, diphenhydramine, or a specific platelet-activating factor antagonist (CV-6209) did not influence the response to endothelin 1. Endothelin 1 significantly decreased net sodium and net chloride absorption and induced a marked increase in prostacyclin release from the serosal surface of stripped colonic mucosa. CONCLUSIONS: Endothelin 1 has a secretory effect in rat colon. Its action seems to be mediated by cyclo-oxygenase products and enteric nerves via the activation of an endothelin A receptor. PMID- 8482448 TI - Restitution of frog gastric mucosa in vitro: effect of basic fibroblast growth factor. AB - BACKGROUND: Rapid re-epithelialization after superficial gastric mucosal injury is caused by migration of persisting viable epithelial cells. Basic fibroblast growth factor (bFGF) has been reported to enhance the healing of experimental duodenal ulcer, but its mode of action is unclear. The present experiments examine whether an effect of bFGF on restitution might contribute to such healing. METHODS: Paired halves of bullfrog fundic gastric mucosa in Ussing chambers were injured by luminal exposure to 1 mol/L NaCl for 10 minutes. RESULTS: Luminal protamine or suramin, both known to interfere with endogenous bFGF, significantly inhibited electrophysiological recovery at neutral luminal pH (pHL). Luminal sucrose octasulfate, which prevents acid degradation of bFGF, and an exogenous, acid-resistant form of bFGF allowed electrophysiological recovery at a pHL of 3.0 that completely prevented restitution in control tissues. Electrophysiological recovery correlated well with morphological restitution. The presence of endogenous bFGF in normal and restituting bullfrog mucosa was confirmed by positive staining with a monoclonal antibody. CONCLUSIONS: It is concluded that rapid epithelial repair after surface injury is at least in part mediated by bFGF. PMID- 8482449 TI - Long-term omeprazole therapy in peptic ulcer disease: gastrin, endocrine cell growth, and gastritis. AB - BACKGROUND: The effects of chronic drug-induced hypergastrinemia on the exocrine and endocrine stomach are still incompletely understood. Chronic hypergastrinemia in rats and humans is associated with gastric argyrophil cell hyperplasia. METHODS: Seventy-four patients with chronic ranitidine-resistant ulcerations were treated chronically with omeprazole (median observation period 48 [6-84] months). RESULTS: Median fasting serum gastrin levels increased from a pretreatment value of 74-145 pg/mL after 3 months. No further increase was observed thereafter. The finding of atrophic gastritis increased from 1.8% to 20.8% after 5 years. A doubling of the mean argyrophil cell volume density (0.36% vs. 0.74% after 5 years; P < 0.01%) was paralleled by a decrease in the normal endocrine cell growth pattern from 64.3% to 33.3% and an increase in micronodular hyperplasia (8.9% vs. 16.7%). These changes correlated with the severity of corpus gastritis and seemed to be more disease- than drug-related. No statistically significant changes were observed in the antral G- and D-cell volume densities under therapy. CONCLUSIONS: Long-term omeprazole therapy in humans results in moderate hypergastrinemia and a significant argyrophil cell hyperplasia, which are correlated to the grade of corpus gastritis. Because hypergastrinemia and gastritis are closely related, it is difficult to quantitatively assess their respective role in this process. PMID- 8482450 TI - Calretinin and calbindin-D28k immunoreactivity in the human gastrointestinal tract. AB - BACKGROUND: Calretinin and calbindin-D28k are similar Ca(2+)-binding proteins previously described in specific central neurons and other cells. METHODS: The immunocytochemical distribution of these two proteins was studied in the human gastrointestinal tract. RESULTS: In gastric and small intestinal endocrine cells, calbindin-D28k immunoreactivity was confirmed, but calretinin immunoreactivity was not found. Nerve cell bodies in both submucous and myenteric ganglia were immunoreactive for calbindin (13% and 38% of total cells, respectively) or calretinin (23% and 21%), some containing both proteins. In nerve processes, calretinin was generally more abundant than calbindin and was found particularly around blood vessels. Calretinin co-localized with immunoreactive vasoactive intestinal peptide, neuropeptide Y, galanin, or substance P in submucous ganglion cells and with substance P in myenteric cells. Calbindin-D28k colocalized with fewer peptides, specifically vasoactive intestinal peptide or galanin in submucous cells. By 8 weeks of fetal development, discrete neuronal localizations for both proteins and for calbindin-D28k in endocrine cells were apparent. CONCLUSIONS: In the enteric neuroendocrine system, calretinin and calbindin-D28k are useful markers that may help elucidate Ca(2+)-mediated functions in health and disease. PMID- 8482451 TI - Endogenous dopamine and duodenal bicarbonate secretion in humans. AB - BACKGROUND: Catechol-O-methyltransferase (COMT) inhibition prevents tissue degradation of catecholamines including dopamine. This study was undertaken to investigate the effect of intraluminal nitecapone, a peripherally acting COMT inhibitor, on duodenal mucosal bicarbonate secretion in humans and to compare the effect with that of the prostaglandin E1 analogue misoprostol. METHODS: The duodenal bulb was isolated by means of a three-balloon six-channel tube as previously described. Basal bicarbonate secretion and secretion after intraluminal administration of 30 and 150 mg nitecapone were determined in 11 healthy subjects. In 7 of these subjects, effects of intraluminal administration of 30 and 150 micrograms of misoprostol were studied in a second experiment. RESULTS: Even the lower dose of misoprostol increased duodenal bicarbonate secretion from 121 +/- 12 to 221 +/- 36 and the lower dose of nitecapone from 149 +/- 18 to 277 +/- 48 microEq.cm-1 x h-1, respectively (P < 0.05). With 150 micrograms of misoprostol or 150 mg of nitecapone there was a further increase in secretion to 296 +/- 33 (P < 0.01) and 421 +/- 36 (P < 0.001) microEq.cm-1 x h-1, respectively. The rise in bicarbonate secretion in response to nitecapone was associated with some increase in the release of prostaglandin E2 to the luminal perfusate. CONCLUSIONS: It seems likely that peripheral COMT inhibition increases duodenal mucosal bicarbonate secretion and protection by inhibition of mucosal degradation of dopamine, an increase similar in magnitude to that obtained by a prostaglandin E1 analogue. PMID- 8482452 TI - Presynaptic inhibition by adenosine A1 receptors on guinea pig small intestinal myenteric neurons. AB - BACKGROUND: Adenosine acts at A1 receptors to inhibit the release of most neurotransmitters. This study tested the hypothesis that both exogenous adenosine (ADO) and tonic release of endogenous ADO act at presynaptic A1 receptors to suppress excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in myenteric neurons. METHODS: Intracellular microelectrodes were used to study actions of ADO, the agonists 2-chloro-N6-cyclopentyl ADO, its 1-deaza derivative, 5'-N-ethylcarboxamido ADO, and CGS 21680 or the antagonists 8 cyclopentyl-1,3-dimethylxanthine, its 1,3-dipropyl analog, and 1,3-dipropyl-8-p sulfophenylxanthine on synaptic behavior in myenteric neurons. RESULTS: Each of the agonists suppressed slow EPSPs in all 35 AH/type 2, 8 of 10 S/type 1, and 7 of 7 nonspiking neurons. ADO also decreased neuronal excitability (n = 63) in AH/type 2 neurons. Agonists suppressed fast nicotinic EPSPs in all 20 S/type 1, 10 nonspiking, and 3 AH/type 2 neurons without having any effect on postsynaptic responses to nicotinic agonists. CCPA was more potent than CGS 21680 in suppressing EPSPs. In 30% of neurons, the only action of antagonists was to block the effect of A1 or A2 agonists on EPSPs. Agonists did not inhibit IPSPs, but unmasked robust slow IPSPs by preventing slow EPSPs. Antagonists acted alone to enhance EPSPs in 70% of neurons. CONCLUSIONS: (1) ADO acts at presynaptic A1 sites to suppress EPSPs in all neurons, (2) IPSPs are revealed by ADO, and (3) ongoing release of endogenous ADO inhibits synaptic transmission. PMID- 8482453 TI - Characterization and mediation of inhibitory junction potentials from opossum lower esophageal sphincter. AB - BACKGROUND: Activating nonadrenergic, noncholinergic (NANC) nerves of the lower esophageal sphincter (LES) hyperpolarizes and relaxes its circular smooth muscle. This relaxation is mediated by nitric oxide (NO) or an NO-containing compound. These studies were undertaken to compare the electrophysiological responses of circular smooth muscle from the LES and esophagus in response to NANC nerve stimulation and to test the hypothesis that NO mediates LES hyperpolarization. METHODS: The transmembrane potential difference was recorded with glass microelectrodes. Nerve-mediated membrane responses were evoked by electrical pulses of 0.5 msec duration and 50 V amplitude. RESULTS: Responses of LES muscle differed from those of the esophageal muscle. The duration of hyperpolarization was much longer in sphincteric muscle. The depolarization that followed hyperpolarization of esophageal muscle was not observed in sphincteric muscle. NG nitro-L-arginine, an inhibitor of NO synthase, attenuated the nerve-induced hyperpolarization. L-arginine, the substrate for NO synthase, antagonized the effect of NG-nitro-L-arginine. Exogenous NO hyperpolarized of the smooth muscle membrane. CONCLUSIONS: These data support the hypothesis that NO or an NO-like compound may mediate nerve-induced hyperpolarization of the opossum LES. PMID- 8482454 TI - Cigarette smoking, alcohol, and the risk of colorectal adenomas. AB - BACKGROUND: The present study was designed to further assess the reported association between cigarette smoking, alcohol, and colorectal adenomas. METHODS: A number of environmental and life-style risk factors were examined in 236 patients with histologically proven adenomas and 409 controls with no adenomas. RESULTS: Age, sex, race, and indication for procedure were similar in cases and controls. Those who had ever smoked were not at increased risk for adenomas compared with those who had never smoked. Years of smoking, cigarettes per day, and total pack-years showed no dose-response effect. Results for men and women were similar. Alcohol was a significant risk factor for men but not for women. Men in the highest quartile of daily caloric intake from alcohol were more than four times more likely than nondrinkers to develop adenomas, with a statistically significant trend in risk from the lowest to the highest quartile. These findings persisted after controlling for other potential risk factors for adenomas. The risk for colon and rectal polyps were similar. Men in the highest tertile of beer consumption were nearly six times more likely to develop adenomas than nondrinkers. CONCLUSIONS: Beer drinking is a risk factor for colorectal adenomas in this population. PMID- 8482455 TI - Percutaneous drainage versus albendazole therapy in hepatic hydatidosis: a prospective, randomized study. AB - BACKGROUND: Recently, drug treatment and percutaneous drainage have been used successfully when treating hepatic hydatid cysts. Until now, there is no published study comparing the relative safety and efficacy of these two forms of treatment. METHODS: In a prospective study, 33 hepatic hydatid cysts were randomly distributed to receive percutaneous drainage (10), albendazole (10 mg.kg 1.day-1 for 8 weeks) plus percutaneous drainage (12), and albendazole alone (11). Patients were serially assessed by clinical and biochemical examinations, ultrasonography, and hydatid serology. RESULTS: On serial ultrasonography, cysts attained heterogeneous echopattern in 18, uniform echogenicity in 11, and disappearance in 3. All 22 cysts treated with percutaneous drainage and only 2 (18.2%) cysts treated with albendazole alone reduced in size and change in echopattern (P < 0.01). Maximum size reduction was observed in cysts treated with a combination of percutaneous drainage and albendazole (P < 0.05). Complications observed with drainage were cyst infection in 2 patients, fever in 3, cyst biliary rupture in 1, and urticaria in 2. These were managed successfully without any mortality. Three patients who received albendazole developed reversible elevation of liver cell enzymes. CONCLUSIONS: It was concluded that percutaneous drainage with albendazole therapy is an effective form of management for hepatic hydatid cysts. PMID- 8482456 TI - Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis. AB - BACKGROUND: Hemodynamic studies have shown the efficacy of nitrates in reducing portal pressure in cirrhosis. We therefore studied the efficacy of isosorbide-5 mononitrate vs. propranolol in the prevention of first bleeding within a prospective controlled trial. METHODS: One hundred eighteen cirrhotics with esophageal varices were blindly randomized to receive 20 mg of isosorbide-5 mononitrate three times a day (n = 57) or propranolol (n = 61) up to the maximum tolerated dose. Both groups also received ranitidine (150 mg/day). RESULTS: The median follow-up was 29 months. Twenty-six patients dropped out (13 in the isosorbide group) because of poor compliance or complications unrelated to treatment. Eighteen patients died (9 in the isosorbide-treated group), 6 due to bleeding. The 1- and 2-year actuarial percentages of patients free of bleeding was 90.8% and 82.2% in the isosorbide-5-mononitrate--and 93.9% and 85.8% in the propranolol-treated groups, respectively (P = NS). These values are higher than those expected from the North Italian Endoscopic Club predicting scores. There were few major side effects in either group. The 2-year survival rate did not differ between the two groups (82.2% vs. 85.4%). CONCLUSIONS: Isosorbide-5 mononitrate administered orally is a safe and effective alternative to propranolol in the prophylaxis of bleeding in cirrhosis. PMID- 8482457 TI - Sinusoidal endothelial cell damage by activated macrophages in rat liver necrosis. AB - BACKGROUND: Massive hepatic necrosis caused by fibrin deposition in the hepatic sinusoids develops with hepatic macrophage activation in rats given endotoxin after administration of heat-killed Corynebacterium parvum. Targeted cells of such macrophages were investigated. METHODS: In C. parvum-treated rats, the pathological appearance of liver cells was serially measured in serum following endotoxin administration and compared with the appearance in the perfusate during closed liver perfusion with endotoxin. RESULTS: Serum activities of tumor necrosis factor, purine nucleoside phosphorylase present in both hepatocytes and sinusoidal endothelial cells, and levels of alanine aminotransferase were higher after 30 minutes, 1 hour, and 3 hours, respectively. Pretreatment of rats with gadolinium chloride, an inhibitor of macrophage function, reduced this liver injury. Although alanine aminotransferase activity remained almost unchanged in the liver perfusate, purine nucleoside phosphorylase activity increased. This increase was reduced when rats were pretreated with gadolinium chloride. There was sinusoidal endothelial cell damage around hepatic macrophages in the liver perfused with endotoxin. CONCLUSIONS: Activated hepatic macrophages may cause sinusoidal endothelial cell damage leading to hepatocyte necrosis in rats given C. parvum and endotoxin. PMID- 8482458 TI - Hepatitis C RNA in liver of chronic hepatitis C patients before and after interferon alfa treatment. AB - BACKGROUND: Successful treatment of chronic hepatitis C with interferon alfa is frequently followed by relapse. Because loss of hepatitis C viral RNA (HCV-RNA) in serum is not predictive of sustained response, the loss of HCV-RNA in liver as a predictor of sustained response was investigated. METHODS: Twenty-one patients with chronic hepatitis C treated with recombinant interferon alpha had HCV-RNA sequences determined in frozen liver tissue before and after treatment and in serum at the end of treatment. Reverse double polymerase chain reaction was used to detect sequences to the 5' nontranslated region of the HCV genome using double nested primers. RESULTS: HCV-RNA disappeared in the liver in 10 of 11 (91%) complete responders whereas it remained detectable in the liver or serum of 7 of 8 (87%) nonresponders. Five complete responders relapsed biochemically during 6 month's follow-up; 4 of these had no detectable HCV-RNA in liver at end of treatment. CONCLUSIONS: Disappearance of HCV-RNA in liver correlates with initial clinical outcome, but as previously reported with serum HCV-RNA, this loss does not necessarily allow prediction of a sustained response. PMID- 8482459 TI - Early-onset autoimmune hepatitis is associated with a C4A gene deletion. AB - BACKGROUND: Autoimmune hepatitis is an immunologically mediated disorder with some similarities to systemic lupus erythematosus, including an association with HLA-A1, B8, DR3. This haplotype includes a C4A, 21-OHA gene deletion. Low serum levels of complement and C4 null alleles have been reported in autoimmune hepatitis, but studies have been at the protein level only. METHODS: Twenty-four white patients with autoimmune hepatitis were studied by Southern blots using a C4A gene complementary DNA probe. HLA A, B, and C typing was determined using standard microcytotoxicity assays, and DR and DQ specificities were determined by restriction fragment length polymorphism analysis. RESULTS: Thirteen of 24 patients had the C4A gene deletion compared with 12 of 90 controls. HLA-A1 and B8 were increased in patients with autoimmune hepatitis, as were HLA-DR3 (DR17), Dw24, DQ2. Patients with a C4A gene deletion presented at a younger age than those without the deletion and had significantly lower serum C3 and C4 levels. The C4A gene deletion was associated with HLA-A1, B8, DR3 in all but 1 patient who was HLA-DR3 negative. CONCLUSIONS: A C4A gene deletion is found in patients with autoimmune hepatitis, especially those presenting at a young age. This complement gene deletion may be an important factor in the development of this disease. PMID- 8482460 TI - Circulating levels of endothelin in cirrhosis. AB - BACKGROUND: Current information concerning endothelin in cirrhosis is conflicting. Plasma endothelin concentration has been found to be increased in some studies and normal or reduced in others. The present study was aimed to investigate the plasma levels of endothelin in cirrhosis and to assess whether it is involved in the renal and hemodynamic disturbances and neurohumoral changes present in this condition. METHODS: Renal function, plasma renin activity, and plasma concentration of aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic factor, and endothelin were measured in 9 healthy subjects, 7 compensated cirrhotics, and 25 cirrhotics with ascites (10 with functional renal failure). RESULTS: Cirrhotics with ascites with and without functional renal failure showed higher endothelin levels (15.6 +/- 6.4 and 15.7 +/- 4.6 pg/mL, respectively; mean +/- SD) than compensated cirrhotics (6.4 +/- 1.8 pg/mL) and healthy subjects (3.4 +/- 1.0 pg/mL) (analysis of variance, F = 21.84; P < 0.001). These patients also showed higher plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic factor, although plasma endothelin levels only correlated significantly with plasma atrial natriuretic factor (r = 0.73, P < 0.001) and antidiuretic hormone concentrations (r = 0.59, P < 0.001). In 7 additional nonazotemic cirrhotics with ascites, plasma renin activity and the plasma concentration of aldosterone and endothelin were measured before and 24 hours after the intravenous administration of a saline solution of human serum albumin. Volume expansion markedly suppressed renin and aldosterone but not endothelin (21.03 +/- 7.34 vs. 23.97 +/- 14.29 pg/mL). CONCLUSIONS: Circulating plasma levels of endothelin are elevated in cirrhosis with ascites and do not decrease following plasma volume expansion. PMID- 8482461 TI - Tumor necrosis factor alpha and interleukin 6 plasma levels in infected cirrhotic patients. AB - BACKGROUND: Patients with liver cirrhosis disclose both increased production and decreased metabolism of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). The present study analyzes the characteristic pattern of these cytokines during sepsis in cirrhotics. METHODS: TNF-alpha and IL-6 plasma levels, measured during 15 days from the onset of cirrhotic decompensation or of the septic event, were compared between 14 infected patients with liver cirrhosis, 18 uninfected decompensated cirrhotic patients, and 35 septicemic patients devoid of liver disease. Cytokines were measured using immunoassays. RESULTS: In infected cirrhotics, initial levels of both TNF-alpha and IL-6 were significantly higher than in noninfected cirrhotic patients (P < 0.0001) or in septicemic patients devoid of cirrhosis (P < 0.001). Initial IL-6 plasma levels (threshold, 200 pg/mL) showed 89% specificity and 100% sensitivity in discriminating cirrhotic decompensation due to infection from that caused by other factors. TNF-alpha and IL-6 plasma levels remained significantly higher for many days in infected cirrhotic patients compared with the other two groups. CONCLUSIONS: Both the profoundly increased initial levels of TNF-alpha and IL-6 and their persistence over days after sepsis onset seem characteristic of the cirrhotic patients. The exact relationship between prolonged exposure to TNF-alpha and poor prognosis in these patients is unknown, but it might represent a unique opportunity for the use of anti-TNF-alpha antibodies during sepsis. PMID- 8482462 TI - In situ kinetics of acinar, duct, and inflammatory cells in duct ligation-induced pancreatitis in rats. AB - BACKGROUND: Acute pancreatitis remains a disease of uncertain pathogenesis. The resolution of the cellular events that underlie the development of pancreatitis may allow for significant advances in therapy. METHODS: A new experimental approach to acute pancreatitis in the rat, i.e., selective ligation of pancreatic ducts and immunohistochemical analysis of cellular kinetics using a panel of monoclonal antibodies, was devised. RESULTS: Immunostaining showed that the majority of the infiltrating cells bore macrophage-specific antigens (ED1 positive). Some neutrophils were also among the cellular infiltrate, but only a few T (OX19-positive) or B (His14-positive) lymphocytes were seen. At a later stage, more than half of the mononuclear cells in the stroma were neither macrophages nor lymphocytes, but possibly fibroblasts. In vivo labeling of proliferating cells with 5-bromo-2'-deoxyuridine and immunostaining showed active proliferation of duct epithelial and wall cells of the interlobular pancreatic duct on days 1 and 2, proliferation of nonacinar cells on days 1-4, and proliferation of acinar cells on days 2-28. CONCLUSIONS: These results indicate an important role of macrophages and the presence of complex processes of degeneration and regeneration in duct ligation-induced pancreatitis. PMID- 8482463 TI - Bovine gallbladder mucin accelerates cholesterol monohydrate crystal growth in model bile. AB - BACKGROUND: Gallbladder mucin accelerates cholesterol crystal nucleation, an early step in the pathogenesis of gallstones. To examine the role of gallbladder mucin in postnucleation gallstone maturation, the influence of mucin on cholesterol monohydrate crystal growth was studied in a novel model system. METHODS: Cholesterol crystals of a uniform size were incubated in model biles at 37 degrees C with varying cholesterol saturation indices. Crystal size was quantitated by measuring the width and length of individual crystals under polarizing light microscopy and calculating average crystal area. RESULTS: Crystal growth was dependent on the degree of cholesterol supersaturation of bile. Bovine gallbladder mucin (0.5-8 mg/mL) accelerated crystal growth in supersaturated model bile in a concentration- and time-dependent fashion compared with control incubations with bovine serum albumin or model bile alone (P < 0.05). Cholesterol crystal growth was accompanied by a progressive decrease in cholesterol saturation and an increase in total cholesterol crystal mass. Crystal growth was also accompanied by a decrease in total crystal number, suggesting net transfer of cholesterol to larger crystals. CONCLUSIONS: The acceleration of cholesterol crystal growth by gallbladder mucin may be of pathophysiological importance in the postnucleation maturation of cholesterol gallstones. PMID- 8482464 TI - Propafenone-induced liver injury: report of a case and review of the literature. AB - A case of an acute cholestatic syndrome associated with use of the antiarrhythmic drug propafenone is reported here. The close time relationship between the administration of the drug and the acute onset of the liver damage, the histological findings, and the reappearance of biochemical signs of liver dysfunction upon rechallenge with the same medication strongly suggest that propafenone was involved in the pathogenesis of this syndrome. Although rare, hepatotoxicity from this widely used antiarrhythmic medication should be kept in mind in the differential diagnosis of sudden cholestatic syndrome of obscure origin. PMID- 8482465 TI - Extracorporeal lipid elimination for treatment of gestational hyperlipidemic pancreatitis. AB - Gestational hyperlipidemia complicated by pancreatitis during the 24th week of gestation has been successfully managed by long-term extracorporeal elimination of triglyceride-rich lipoproteins. Three modes of treatment (plasma exchange, immunospecific apheresis, and a combination of both treatments) were compared for efficacy as therapy for metabolic derangements, altered blood rheology, and the loss of immunoglobulins. Treatments were performed by means of a peripheral venovenous approach. A combination plasma exchange/apheresis technique was highly effective; the loss of immunoglobulins remained acceptable. Clinical symptoms of pancreatitis subsided within 24 hours of the first treatment. A relapse during the 32nd week of gestation necessitated treatments more frequently than once a week. At the 36th week of gestation, after confirming lung maturity as indicated by a lecithin-sphingomyelin ratio of > 2.0, a cesarean section was performed. A healthy boy was delivered (2470 g; Apgar score, 9/10). This is the first report to show that long-term extracorporeal elimination of lipoproteins is a highly effective treatment of hyperlipidemic gestational pancreatitis. PMID- 8482466 TI - Intraluminal pancreatic candidiasis presenting as recurrent pancreatitis. AB - An 88-year-old man with closely spaced attacks of acute pancreatitis who was found to have ductal changes of chronic pancreatitis with multiple noncalcified intraluminal filling defects during endoscopic retrograde pancreatography is presented. These defects proved to be fungus balls made up of Candida albicans. He was treated with longitudinal pancreaticojejunostomy and oral fluconazole and has since remained recurrence free (30 months). It is suggested that Candida superinfection may occur in a chronically dilated pancreatic duct and may contribute to symptomatic recurrent inflammation of the pancreas. PMID- 8482467 TI - Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. AB - Hereditary nonpolyposis colorectal cancer (HNPCC) dates to Warthin's description of family G, which he began studying in 1895. Warthin's observations were not fully appreciated until 1966 when two families with an autosomal dominant inheritance pattern of nonpolyposis colorectal cancer (CRC) and endometrial cancer were described. This condition was first termed the "cancer family syndrome" and was later renamed HNPCC. Some have proposed that HNPCC consists of at least two syndromes: Lynch syndrome I, with hereditary predisposition for CRC having early (approximately 44 years) age of onset, a proclivity (70%) for the proximal colon, and an excess of synchronous and metachronous colonic cancers and Lynch syndrome II, featuring a similar colonic phenotype accompanied by a high risk for carcinoma of the endometrium. Transitional cell carcinoma of the ureter and renal pelvis and carcinomas of the stomach, small bowel, ovary, and pancreas also afflict some families. Current estimates indicate that HNPCC may account for as much as 6% of the total CRC burden. There are no known premonitory phenotypic signs or biomarkers of cancer susceptibility in the Lynch syndromes. This report will summarize current knowledge, with emphasis on the manner in which this knowledge can be employed effectively for diagnosis and management of HNPCC. PMID- 8482468 TI - Gluten sensitivity and latency: can patterns of intestinal antibody secretion define the great 'silent majority?'. PMID- 8482469 TI - Prolonged achlorhydria and gastric neoplasia: is there a causal relationship? PMID- 8482470 TI - Cyclosporin, the biology of the bile canaliculus, and cholestasis. PMID- 8482471 TI - Hyperlipidemic gestational pancreatitis. PMID- 8482472 TI - Hospital credentialing standards for physicians who perform endoscopies. AB - This document was developed to guide hospitals in making credentialling determinations involving endoscopy. Granting hospital privileges to a physician with inadequate qualifications obviously has important patient-care, economic, and legal implications. Particularly when privileges involve expensive, invasive procedures such as endoscopy, the prudent hospital will determine if the applicant for privileges has the training and experience needed to ensure competence in the procedure and in translating the information gained from it into an appropriate course of action. PMID- 8482473 TI - What constitutes endoscopic competence? PMID- 8482474 TI - Zinc in the treatment of Wilson's disease: how it works. PMID- 8482475 TI - Nausea and vomiting in pregnancy and cutaneous electrogastrogram. PMID- 8482476 TI - More problems with aspirin: it may cause appendicitis. PMID- 8482477 TI - Differing chemical content of the neuronal populations of submucosal ganglionic plexus of the enteric nervous system. PMID- 8482478 TI - Hyperdynamic circulation in cirrhosis: physiology or pathophysiology? PMID- 8482479 TI - Absence of false elevations with Kodak Ektachem lipase. PMID- 8482480 TI - Etiology of membranous obstruction of the inferior vena cava. PMID- 8482481 TI - Rat gastric alcohol dehydrogenase activity and ethanol metabolism. PMID- 8482482 TI - Omeprazole and gastric polyposis in humans. PMID- 8482483 TI - NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions. AB - 1. NS-398 (N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide) is a new non steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. 2. The anti-inflammatory potency of NS-398 in rat carrageenin-induced edema was as potent as that of indomethacin and 8 times more potent than diclofenac. In rat adjuvant arthritis, NS-398 showed a therapeutic effect comparable to that seen with loxoprofen but less than that seen with indomethacin and diclofenac. 3. The analgesic potency of NS-398 in rat adjuvant arthritic pain was much the same as that of indomethacin, and was about 3-5 times higher than that of diclofenac and loxoprofen. In the Randall-Selitto method in rats, NS-398 was 2-7 times as potent as loxoprofen, diclofenac and indomethacin. In acetic acid-induced writhing in mice, NS-398 was equipotent to indomethacin and diclofenac. 4. In LPS-induced fever in rats, NS-398 was 1.5-4.5 times as potent as loxoprofen and indomethacin, but less potent than diclofenac. 5. NS-398 produced little gastric ulceration in doses of up to 1000 mg/kg, while reference drugs produced distinct stomach lesions in doses of 10-30 mg/kg. 6. NS-398 inhibited prostaglandin (PG) endoperoxide synthase from sheep seminal vesicle microsomes less potent than that of ibuprofen. PMID- 8482484 TI - Acetylcholinesterase changes in hearts with sinus rhythm and atrial fibrillation. AB - 1. Clinical and experimental evidence suggest that changes in the autonomic tone play a role in the pathogenesis of atrial fibrillation. 2. We have studied the distribution of molecular forms of acetylcholinesterase (AChE) in atrial biopsies obtained from individuals without arrhythmias and in patients with atrial fibrillation. 3. Analysis of the distribution of globular and asymmetric AChE forms, showed a decrease in the amount of the globular forms of biopsies taken from atria during fibrillation. 4. This study is the first attempt to characterize the molecular forms of AChE in the human heart of patients with sinus rhythm and chronic atrial fibrillation. PMID- 8482485 TI - The effect of oral vanadyl treatment on the reactivity of tracheal smooth muscle obtained from insulin-dependent diabetic rats. AB - 1. In this study, we investigated the contractile effects of acetylcholine (ACh) and KCl in tracheas obtained from 12-13 wk insulin-dependent (ID)-diabetic rats. 2. The maximum contractile responses to ACh and KCl were significantly increased in ID-diabetic rat tracheas compared with those from controls. But the sensitivity (pD2 values) of ID-diabetic tracheas to these agents were not significantly altered relative to controls. 3. The alterations which occurred in ID-diabetic rats were prevented with oral vanadyl treatment during a 10 wk period. PMID- 8482486 TI - Basal and histamine-induced gastric acid secretion in alloxan diabetic rats. AB - 1. Effects of alloxan-induced diabetes on the rat gastric acid secretion were investigated using a number of biostatistical models described earlier. 2. Histamine-induced gastric acid secretion was found to be decreased in alloxan diabetic rats when compared with their age-matched controls. 3. Basal acid secretion was also decreased depending on experimentally-induced diabetes. 4. The above results strongly suggest that alloxan-induced diabetes depresses vagal activity and H2-receptor activity in the stomach. PMID- 8482487 TI - Subtype of muscarinic receptors mediating relaxation and contraction in the rat iris dilator smooth muscle. AB - 1. Carbachol produced a relaxation of dilator muscle at a concentration lower than 1 microM and a contraction at a concentration higher than 1 microM. 2. We studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, himbacine, the M3-selective antagonist, 4-diphenyl-acetoxy-N methylpiperidine methiodide (4-DAMP) and the non-selective antagonist, atropine, on carbachol-induced relaxation and contraction of the rat iris dilator smooth muscle. All the antagonists competitively inhibited both the responses to carbachol. 3. In relaxation and contraction, the low affinity of pirenzepine and himbacine suggest that the rat iris dilator smooth muscle receptors are not of the M1 and M2 subtypes. In contrast, 4-DAMP potently inhibited the carbachol induced relaxation and contraction with affinities similar to those reported for the M3 subtype. 4. Carbachol-induced relaxation and contraction of the rat iris dilator appears to be mediated through a homogeneous population of M3 subtype. PMID- 8482488 TI - Josamycin concentrations in radicular cysts following a single oral administration. AB - 1. Josamycin concentrations in cyst wall (wall) and cyst fluid (fluid) of radicular cyst and serum following a single oral administration of josamycin (600 mg) were assayed by a paper disk method. 2. The mean peak josamycin concentrations in wall, fluid and serum occurred at 1.5, 2 and 1.5 hr, respectively, and were 1.33 micrograms/g, 0.53 and 0.74 micrograms/ml, respectively. 3. The mean concentration ratios of wall/serum, fluid/serum and fluid/wall at the peak times (1.5, 2 and 2 hr) were 1.80, 0.64 and 0.42, respectively. 4. Josamycin concentrations in wall and fluid at the peak time exceeded MIC for 80% for clinically isolated strains of alpha-hemolytic Streptococci. PMID- 8482489 TI - Interaction of AZA analogs of chlorpromazine with the dopamine D2 receptor. AB - 1. Permanently charged AZA analogs of chlorpromazine inhibited the binding of [3H]spiperone and antagonized the apomorphine-induced inhibition of the potassium evoked release of [3H]acetylcholine. 2. The AZA analogs were more potent in binding affinity and antagonist activity than the trimethylammonium analog of chlorpromazine but less potent than chlorpromazine. 3. These results suggest that it is possible to enhance the binding of the permanently charged trimethylammonium analog of chlorpromazine by the addition of a functional group near the quaternary nitrogen which is capable of forming a hydrogen bond with the D2 dopamine receptor. 4. However, it appears that for optimal binding, as achieved with chlorpromazine, the hydrogen-bonding proton should be on the charged nitrogen. PMID- 8482490 TI - Effects of an inhibitor of GABA-aminotransferase (gamma-vinyl-GABA) on the spatial navigation deficit induced by nicotinic blockade. AB - 1. The present study investigated whether stimulation of the GABA-ergic system affects spatial navigation (water-maze, WM) deficit induced by nicotinic blockade (mecamylamine). 2. The effects of various doses of gamma-vinyl-GABA (GVG: 50, 150 and 300 mg/kg) and mecamylamine (2.5 and 10 mg/kg) were examined alone and in combination. 3. GVG at the dose 150 mg/kg alone did not impair the performance of rats in the WM task. 4. Mecamylamine at the dose 2.5 and 10 mg/kg clearly impaired the performance of rats in WM task. 5. When the two drugs were co administered, no interaction between mecamylamine and GVG was observed. 6. Combined nicotinic and muscarinic blockade did not interact as well with GVG administration. 7. Our results do not provide support for any interaction between cholinergic and GABA-ergic mechanisms. PMID- 8482491 TI - The effects of acetylcholine on insulin-dependent and non-insulin-dependent diabetic rat tracheal segments. AB - 1. In the present study, the contractile effects of acetylcholine (Ach) were investigated in isolated tracheal strips obtained from insulin-dependent (ID) and non-insulin-dependent (NID) diabetic rats. 2. The maximum responses to Ach were significantly decreased in 5-6 week ID diabetic rat tracheal segments compared with those from controls but, the sensitivity (pD2 values) of ID diabetic tracheas to Ach were not significantly altered relative to corresponding controls. 3. Tracheas isolated from 11-12 week NID diabetic rats exhibited reduced maximal contractile effect of Ach and also sensitivity (pD2 values) of NID diabetic tracheas to Ach were significantly decreased when compared to control rat tracheas. 4. Insulin treatment of both group of diabetic rats for 10 days corrected the changes observed in diabetic tracheas. PMID- 8482492 TI - The effects of glyburide and insulin on the cardiac performance in rats with non insulin-dependent diabetes mellitus. AB - 1. The effects of glyburide were studied on the myocardial contractile force and heart rate in the atria isolated from non-diabetic and non-insulin-dependent diabetic rats (diabetic). 2. In order to examine the myocardial changes in the alloxan model of non-insulin-dependent diabetes, atrial functions of 11-week old diabetic rats were evaluated by comparing with the atria from their age-matched controls. 3. Diabetic atria were found to possess an increased contractile force and reduced inotropic responses to isoprenaline as a consequence of non-insulin dependent diabetes induced by neonatal alloxan injection. 4. However, no significant change was observed in the heart rate of diabetic atria in response to isoprenaline when compared with controls. 5. Since apparent affinity constant (pD2 value) calculated for the inotropic response of diabetic atria to isoprenaline was also reduced, it might be suggested that non-insulin-dependent diabetes causes a decrease in the beta-adrenoceptor affinity of the rat atria. 6. Glyburide treatment (5 mg/kg/day per os) for 3 weeks was able to improve the reduced responsiveness of rat atria due to non-insulin-dependent diabetes as well. The results obtained in this study indicated that glyburide possesses an improving effect on the decreased beta-adrenergic responses of rat atria with non insulin-dependent diabetes mellitus. PMID- 8482493 TI - Pyrazine CH- and NH-acids. Antithrombotic activity and chromatographic behaviour. AB - 1. A series of newly synthesized pyrazine CH- and NH-acids was subjected to analytical and pharmacological studies. 2. The compounds were chromatographed in HPLC systems employing three reversed-phase columns and methanol-buffer solvents of various composition at acidic, neutral and alkaline pH. 3. Chemometrical analysis by the principal component method allowed for ordering of the compounds on a plane determined by the first two principal component axes. 4. Pharmacological tests were done for representatives of the series of compounds. 5. An in vivo antithrombotic assay on mice proved diversified bioactivity within the group of agents. 6. Attempts were undertaken to relate chromatographic behaviour to antithrombotic activity. 7. Based on the results obtained, an approach was proposed to reduce the number of pharmacological tests in selecting the most promising agents. PMID- 8482494 TI - Effect of testosterone on the response of young rat vas deferens to norepinephrine. AB - 1. Following in vitro treatment with 12 microM 6-hydroxy-dopamine, 2 microM B oestradiol, 0.1 microM propranolol and 10 microM cocaine vasa deferentia isolated from young rats (21-23 days old) showed supersensitivity to norepinephrine (NE) compared to those from adult (3 months old) rats. 2. The pA2 values for prazosin were higher in young (9.6 +/- 0.1) than in adult (8.3 +/- 0.1) rat vas deferens, with the slopes of the Schild plots not different from 1.0 (0.78 +/- 0.26 and 1.14 +/- 0.14, respectively). 3. The treatment of young rats with a single dose of testosterone abolished the supersensitivity to NE and the higher affinity for prazosin. 4. We conclude that there is a reduction of neuronal NE uptake and a decrease in the sensitivity to NE in the vas deferens as the rat matures sexually. 5. Testosterone induces a decrease in the sensitivity to NE, probably via an action on the alpha 1-adrenoceptor population and the sympathetic nerve discharge in this organ. PMID- 8482495 TI - Endogenous dopamine differently affects N-[1-(2 benzo(b)thiophenyl)cyclohexyl]piperidine and cocaine binding to the dopamine uptake complex. AB - 1. [3H]N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP) labels in vivo the dopamine uptake complex in the mouse striatum. 2. In mice treated with gamma butyrolactone (GBL, 400 mg/kg), [3H]BTCP specific binding was increased and ID50 values of BTCP and cocaine for the prevention of [3H]BTCP binding were significantly lowered. 3. In GBL-treated mice, cocaine (5 mg/kg, s.c.) had no effect on the BTCP ID50 value, whereas GBR 12783 (2 mg/kg, s.c.) increased it significantly. 4. Thus in vivo, endogenous dopamine and cocaine are competitive and non-competitive inhibitors, respectively, of the binding of [3H]BTCP. PMID- 8482496 TI - The effects of propranolol on skeletal muscle contraction, lipid peroxidation products and antioxidant activity in experimental hyperthyroidism. AB - 1. The mean levels of lipid peroxidation products, namely conjugated diene and malonaldehyde, were increased in the soleus muscles of hyperthyroid cats, while the mean glutathione peroxidase activity was decreased. No corresponding similar changes were noted in the fast extensor digitorum longus muscles and serum. 2. Propranolol administration prevented the increase in conjugated diene level in the soleus muscles of hyperthyroid cat but not the malonaldehyde level. It also prevented the reduction in glutathione peroxidase activity in the slow oxidative soleus muscles of hyperthyroid cats. 3. Maximal twitch tension, subtetanic tension and maximum tetanic tension of soleus and EDL muscles were reduced in hyperthyroid cats. Propranolol administration for 5 weeks to hyperthyroid cats did not prevent the reduction in tension of contractions of these muscles. 4. It is suggested that lipid peroxidation might not be responsible for the myopathy in hyperthyroidism and propranolol administration does not improve skeletal muscle function in hyperthyroid animals. PMID- 8482497 TI - Analgesic effects of intracerebroventricular administration of calcium channel blockers in mice. AB - 1. The antinociceptive action of calcium channel blockers administered intracerebroventricularly to mice using the acetic acid writhing test was studied. 2. The drugs produced dose-dependent inhibition of the number of writhes induced by the intraperitoneal administration of 10 ml/kg of 0.6% acetic acid. 3. The CaCBs may be ranked from most to least potent as follows: verapamil > nimodipine > diltiazem > flunarizine > nifedipine > cinnarizine. 4. Since naloxone pretreatment was not able to inhibit the antinociception produced by CaCBs an opioid mechanism of action is excluded. 5. It is suggested that CaCBs can induce analgesia through a decrease in cellular Ca2+ availability, increasing the nociceptive threshold. PMID- 8482498 TI - Hypoxia-induced coronary flow changes in the perfused rat heart: effects of high L-carnitine concentrations. AB - 1. Hemodynamic effects of physiological (0.04 and 0.07 mM) and high (8, 15 and 25 mM) L-carnitine (LC) concentrations were tested on the normally oxygenated and hypoxic perfused rat heart. 2. No effect was detected on aerobic hearts, whereas a dose-dependent rise in coronary flow (CF) during both the hyperemic and constrictive phases was observed in hypoxic hearts with 8, 15 and 25 mM LC. This action was apparently unrelated to a resting tension (RT) improvement, which was observed only with 25 mM LC. 3. When 11 mM glucose was replaced by 11 mM mannitol in the perfusion buffer, LC effects on the hyperemic phase were abolished; however, 25 mM LC resulted in CF-values still significantly higher than those detected without the drug, though RT was similar in these glucose-free groups. 4. It may be concluded that LC is ineffective on the perfused rat heart in aerobic conditions, whereas high LC concentrations can enhance CF only during hypoxia, these effects being independent of heart function improvements and partly unrelated to glucose presence. PMID- 8482499 TI - Neuroprotective effect of vinconate against postischemic alterations in binding of [3H]SCH 23390 in the gerbil brain. AB - 1. We investigated alterations in dopamine D1 receptors in the striatum and hippocampus after transient cerebral ischemia in gerbils using [3H]SCH 23390 autoradiography. 2. We also examined the effect of vinconate against the alterations in dopamine D1 receptors after transient ischemia. 3. Transient ischemia was induced for 10 min, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 min before ischemia. 4. [3H]SCH 23390 binding showed no significant alterations in the striatum and hippocampus 5 hr after ischemia, whereas severe reduction in these areas was found after 7 days of recirculation. 5. Vinconate showed no significant alterations in [3H]SCH 23390 binding in the striatum and hippocampus except for a decrease in the hippocampal CA3 sector and dentate gyrus 5 hr after ischemia. By contrast, vinconate prevented a significant reduction in [3H]SCH 23390 binding in the striatum, hippocampal CA3 sector, hilus, and dentate gyrus 7 days after ischemia. 6. Vinconate inhibited lipid peroxidation in rat brain homogenates in a concentration-related manner. 7. These results indicate that free radicals generated from abnormal dopamine metabolism may play a key role in the development of ischemic brain damage. Furthermore, they suggest that vinconate prevents ischemic brain damage by inhibiting lipid peroxidation. PMID- 8482500 TI - Effects of class I antiarrhythmic drugs on mitochondrial ATPase activity in guinea pig heart preparations. AB - 1. The effects of three class I antiarrhythmic drugs quinidine, lidocaine and lorcainide on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase, EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. 2. All three drugs inhibited the enzyme activity in a concentration-dependent fashion. 3. Lorcainide was the most potent, exerting inhibitory effects in the range of less than 1.0 nM-2.0 mM, with IC20 and IC50 values of 9.4 +/- 0.6 nM and 87.2 +/- 5.5 microM. However, in the range of approx. 10 nM-10 microM, the enzyme response decreased only slightly with increasing lorcainide concentrations. 4. Quinidine and lidocaine, on the other hand, inhibited the enzyme activity in the range of 1.0 microM-100 mM. 5. The IC20 and IC50 values for quinidine were 0.92 +/- 0.04 mM and 4.8 +/- 0.6 mM and for lidocaine were 115 +/- 6 microM and 2.3 +/- 0.3 mM. 6. The results show that all three drugs inhibit mitochondrial ATPase activity and that lorcainide is the most potent. 7. These inhibitory effects may be related to the lipophilicity and membrane stabilizing activity of this class of antiarrhythmic drugs. PMID- 8482501 TI - Positive chronotropic and inotropic responses to lysophosphatidylcholine are mediated by norepinephrine released from myocardial sympathetic nerve terminals. AB - 1. The effects of beta-adrenoceptor blockade and reserpinization on the positive chronotropic and inotropic responses to lysophosphatidylcholine (LPC) were examined in isolated atrial and ventricular preparations from rat hearts. 2. The positive responses to 10(-4) M LPC were about 40-55% of those to 10(-5) M norepinephrine (NE) in each preparation. 3. The responses to LPC in the presence of propranolol or in the reserpinized preparations were significantly smaller than the corresponding values obtained in control preparations, and were about 10 25% of those to NE. 4. It was concluded that positive chronotropic and inotropic responses to LPC are at least partially mediated by release of NE from myocardial sympathetic nerve terminals. PMID- 8482502 TI - Duration-dependent variability in the responses of diabetic rat aorta to noradrenaline and 5-hydroxytryptamine. AB - 1. The responsiveness of isolated aortic rings from 1, 4 and 12 week streptozotocin-induced diabetic rats to noradrenaline (NA) and 5 hydroxytryptamine (5-HT) were compared with those of non-diabetic controls under standard organ bath procedure. 2. There were significant increases in the maximum contractile responses to both agents after 1 and 4 weeks but not after 12 weeks of diabetes mellitus. 3. The variable responses show that duration-dependent functional changes occur in the course of streptozotocin diabetes in rats. PMID- 8482503 TI - Neuropeptide Y-induced inositol phospholipid hydrolysis in blood vessels from normotensive and spontaneously hypertensive rats. AB - 1. Neuropeptide Y (NPY) increased inositol phosphate (IP) formation in the femoral artery and vein of adult Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. Noradrenaline (NA, 10(-6) M) induced IP accumulation in both strains of rats. 3. Subthreshold concentrations of NPY (3 x 10(-9) M for femoral vein and 10(-8) M for femoral artery) failed to modify NA (10(-6) M) induced IP formation in both vessels. 4. These results suggest that the direct contractile effects but not the potentiation of NA-induced contractions may be directly linked to phosphatidylinositol turnover in adult SHR and WKY rats. PMID- 8482504 TI - Histamine H1 receptor binding sites in mouse uterine horns. AB - 1. The specific binding of both [3H]histamine and [3H]pyrilamine to crude membrane preparations obtained from mouse uterine horns was studied with the aid of radioligand binding techniques. 2. Saturation isotherms and binding of 300 nM of [3H]histamine in the presence of increasing concentrations of unlabelled histamine suggested the presence of two populations of [3H]histamine binding sites (IC50: 56 +/- 5.6 nM and 100 +/- 9.8 microM, respectively). 3. Pyrilamine displaced the high affinity binding site (IC50: 100 +/- 10 nM), while cimetidine displaced the low affinity one (IC50: 98 +/- 10 microM). 4. Saturation curve analysis by using [3H]pyrilamine as radioligand, revealed that H1 binding site varied according to the predominance of sexual hormones (Kd: 29 nM; 102 nM and 130 nM in uterine membranes from ovariectomized, diestrous and estrous, respectively). At the end of pregnancy Kd was found to be 71.1 nM. PMID- 8482505 TI - Morphological and electrophysiological changes induced by calcium ionophores (A23187 and X-537A) in spontaneously beating rabbit sino-atrial node cells. AB - 1. Effects of calcium ionophores (A23187 and X-537A) on the spontaneously beating sino-atrial (SA) node cells of rabbit heart were examined using electron microscopic and an electrophysiological techniques. 2. During exposure to A23187 or X-537A (2 x 10(-5) M), the cycle length was significantly prolonged by 11% (n = 12) or 118% (n = 11), respectively. But neither ionophore affected other action potential parameters. 3. X-537A (2 x 10(-5) M) induced irregular rhythm (dysrhythmia), probably due to cellular calcium overload. Similarly, ouabain (3 x 10(-7) M) also elicited dysrhythmia. In the presence of isoproterenol (ISP, 10( 7) M), X-537A potentiated dysrhythmia, and A23187 newly induced it. 4. In ultrastructural analyses, X-537A caused swelling of the cisternae of Golgi apparatus within 10 min, whereas A23187 and ouabain did not produce any changes even after 30 min-application. 5. Addition of high Ca2+ (10 mM) and/or ISP (10( 7) M) to X-537A produced a further dilation and vacuolization. In A23187 or ouabain, however, the addition of Ca2+ and ISP did not cause any changes, even during dysrhythmia. 6. These results indicate that X-537A elicited a more potent calcium overload than A23187, and that a discrepancy between ultrastructural damages and electrical changes exists. PMID- 8482506 TI - Preferential decarboxylation of L-threo-3,4-dihydroxyphenylserine in rat renal tissues. AB - 1. Administration of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS; 3, 10 and 30 mg/kg, i.p.) produced a dose-dependent increase in the tissue levels of both noradrenaline and its deaminated metabolite 3,4-dihydroxyphenylglycol (DOPEG) in the rat jejunum, liver and renal cortex, but not in the left ventricle. 2. The accumulation of noradrenaline and DOPEG after the administration of L-threo-DOPS (30 mg/kg, i.p.) was also found to be a time-dependent effect, reaching its maximum 15 min after the injection and then declining progressively. 3. The accumulation of noradrenaline and DOPEG after L-threo-DOPS (30 mg/kg, i.p.) was found to be similar in control and 6-OHDA treated rats and completely prevented by previous treatment with benserazide. 4. Administration of L-threo-DOPS (30 mg/kg) produced an increase in plasma levels of noradrenaline and DOPEG; this effect was maximum, for both noradrenaline (6.2-fold increase) and DOPEG (3.4 fold increase), at 30 min after the injection of L-threo-DOPS. 5. The results presented here support the view that most L-threo-DOPS is decarboxylated into noradrenaline by non-neuronal AAAD, a reaction occurring predominantly in renal tissues. PMID- 8482507 TI - Des-tyrosine-gamma-endorphin effects on morphine analgesia in mice. AB - 1. The effects that were induced by a beta-lipotropin fragment des-tyrosine-gamma endorphin (DT gamma E) devoid of opiate activity that was administered intraperitoneally or intracerebroventricularly to mice under morphine analgesia were investigated. The interaction of this peptide with the analgesic effects of morphine was examined using the hot plate and the tail flick test. 2. Intraperitoneal acute treatment with DT gamma E did not change the analgesic effects of morphine. 3. Intraperitoneal semi-chronic treatment performed for 4 days with DT gamma E enhanced morphine analgesic effects. 4. The intracerebroventricular acute treatment with DT gamma E reduced morphine analgesia in a dose-dependent way. 5. These results indicate that DT gamma E, although devoid of opioid activity per se, may interact with the opioid system, probably through an indirect mechanism. PMID- 8482508 TI - Effect of potassium on the contractile response of the rat detrusor muscle to field stimulation at increasing calcium concentrations. AB - 1. At 0.6 and 1.8 mM calcium, increasing the potassium concentration from 2.5 to both 7.5 and 12.5 mM significantly increased the contractile response to field stimulation at 0.5, 1, 2 and 4 Hz. There were no effects on the contractile responses to 8, 16, 32 and 64 Hz. 22.5 mM potassium significantly reduced the contractile response to all frequencies of stimulation. 2. At 5.4 mM calcium, the contractile responses to all frequencies in the presence of 2.5, 7.5 and 12.5 mM potassium were similar. The responses to all frequencies of stimulation in the presence of 22.5 mM potassium were significantly reduced. 3. In general, the relative responses to low frequencies of stimulation were significantly greater in the presence of 5.4 mM calcium than in the presence of 0.6 or 1.8 mM calcium. 4. The magnitude of the inhibition in the presence of 22.5 mM potassium was inversely proportional to the extracellular calcium concentration, i.e. the lower the calcium concentration, the greater the inhibition. 5. The bladder base responded to alterations in the potassium and calcium concentrations similarly to the bladder body. 6. In conclusion, increasing the potassium concentration from 2.5 mM (normal bath concentration) to 7.5 and 12.5 mM significantly enhanced the contractile response to low frequency stimulation at both 0.6 and 1.8 mM (normal bath concentration) calcium. PMID- 8482509 TI - Maternally-mediated developmental lithium toxicity in the mouse. AB - 1. Breast fed maternally-mediated developmental LiCl toxicity was determined in mice offspring as a function of offspring's gender and duration of maternal intake of LiCl (1 mEq). 2. The female offspring were more sensitive than the males to major organ weight changes by maternal exposure to LiCl. 3. Maternal intake of LiCl from preconception until weaning of the nurslings induced offspring hepatic alcohol dehydrogenase and heart lactate dehydrogenase in both sexes which was isoenzyme specific for the latter. 4. The offspring also showed induction of liver aldehyde dehydrogenase but only as consequences of postnatal exposure to LiCl. 5. The results indicate offspring developmental toxicity as a consequence of maternal exposure to Li salts and breast feeding. PMID- 8482510 TI - A possible mechanism for increased cerebrovascular permeability in diabetic rats: effects of insulin and 2-deoxy-glucose. AB - 1. Cerebrovascular permeability estimated as Evans blue extravasation significantly increased during insulin-induced hypoglycemia in both non-diabetic and diabetic rat groups. 2. Cerebrovascular permeability also increased significantly during 2-deoxy-glucose-induced intracellular glycopenia in both groups. 3. When a blood glucose level was fixed, cerebrovascular permeability showed no more significant change despite the hyperinsulinemic state in both groups. 4. Results suggest that hypoglycemia and/or intracellular glycopenia seems to be the major factor for increases in cerebrovascular permeability. PMID- 8482511 TI - Current trends in the study of potassium channel openers. AB - Some eight years ago it was found that certain smooth muscle relaxants exert their effect by opening a specific K+ channel resulting in cell membrane hyperpolarization. The use of K+ channel openers (cromakalim, pinacidil and RP 52891) and compounds which antagonize their actions (glibenclamide, phentolamine and alinidine) has enabled a great deal of research to be performed into the role of this K+ channel, not only in smooth muscle, but also in cardiac and skeletal muscle as well as neural and endocrine organ function. Much of the attention has centred on the smooth muscle relaxant actions of the K+ channel openers, since they have potential therapeutic use in disorders involving smooth muscle over reactivity such as hypertension and asthma. More recently the cardiac actions of the K+ channel openers have become the focus of interest. Although there appear to be good theoretical reasons why K+ channel openers may be of use in some arrhythmias and in ischaemic heart disease there are major hurdles to overcome. In particular, given that the effect of these compounds on vascular smooth muscle occurs at a concentration 20- to 100-fold lower than that required to produce cardiac effects, it is likely their therapeutic usefulness will be limited until a breakthrough in cardiac/vascular selectivity is made. There is also growing interest in endogenous K+ channel openers and the physiological role of the K+ channel which they open. Opening of K+ channels, either spontaneously or by endogenous regulators, could possibly be an important hypotensive mechanism both under normal conditions and in a number of pathological conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482512 TI - The complex interaction of ATP and UTP with isolated hepatocytes. How many receptors? AB - 1. ATP exerts multiple receptor-mediated effects on isolated hepatocytes: glycogenolysis through the activation of glycogen phosphorylase (cAMP independent, IP3/calcium-mediated), inactivation of glycogen synthase, inhibition of the glucagon effect on cAMP, activation of phospholipase D. The fact that some of these effects can be selectively altered and that they are not, or differently, reproduced by some other analogues of ATP, suggests the presence of more than one receptor. (i) Pertussis toxin abolishes the anti-glucagon effect of ATP without affecting its glycogenolytic effect. (ii) Single cell calcium measurements reveal major differences between ATP and ADP, (iii) 2MeSATP and ADP beta S, in clear contrast to ATP, barely increase the levels of IP3 and their glycogenolytic effects is completely blocked by phorbol ester treatment of hepatocytes. (iv) 2MeSATP differs from ADP beta S since it has no anti-glucagon effect. 2. Effects of UTP on isolated hepatocytes so far do not show any difference with effects of ATP, suggesting interaction with the same receptor(s). 3. It is proposed that liver plasma membranes contain (at least) three different receptors mediating (a) the activation of phospholipase C, (b) the activation of phospholipase D and (c) the inhibition of adenylate cyclase. PMID- 8482513 TI - Effects of oblongine chloride, an alkaloid from Leontice leontopetalum on guinea pig isolated smooth muscle and heart. AB - 1. The effects of (-)oblongine chloride, a quaternary alkaloid from Leontice leontopetalum, on guinea-pig isolated ileal longitudinal segments, main pulmonary artery rings, spontaneously-beating atrium and isolated perfused heart were studied. 2. Oblongine chloride (3 x 10(-5)-10(-3) M) caused concentration dependent relaxation of ileum, an effect which was not blocked by propranolol (10(-6) M) alone or in combination with prazosin (3 x 10(-8) M), or by indomethacin (10(-6) M), but was reduced by desensitization of the preparation by prior exposure to 3 x 10(-5) M ATP and, at high concentrations of oblongine, by a combination of propranolol and yohimbine (3 x 10(-6) M). 3. Oblongine chloride (10(-5)-3 x 10(-3) M) caused concentration-dependent relaxation of epinephrine precontracted pulmonary artery. This effect was not affected by propranolol or by indomethacin but was significantly attenuated by pretreatment with 3 x 10(-5) M ATP and potentiated by pretreatment with quinacrine (10(-5) M). 4. Oblongine chloride (10(-5) M-3 x 10(-3) M) caused concentration-dependent increase in the contractility but did not affect the rate of the atrium. Similar effects were obtained with isolated perfused heart except that large concentrations of oblongine (10(-3), 3 x 10(-3) M) inhibited both contractility and rate of the heart. The inotropic effects of oblongine on the atrium were not blocked by propranolol or indomethacin but were significantly blocked by quinacrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482514 TI - Peripheral administration of taurine antagonizes morphine-induced analgesia in mice. AB - 1. A single i.p. dose of taurine (25 mg/mouse) given to mice 3 hr before an i.p. injection of morphine (0.1 mg/mouse) decreased the analgesic response of the animals to morphine. 2. Neither a lower dose of taurine nor the same dose of another amino acid was effective. 3. The analgesic response to morphine was also reduced by inclusion of taurine in the drinking water. 4. The results of the present study indicate that peripherally administered taurine antagonized morphine-induced analgesia, similar to a previous report that taurine administered centrally, diminished the analgesic response to a centrally injected opioid peptide. PMID- 8482515 TI - The vascular relaxing effect of a factor released by rat atria distension. AB - 1. In order to develop a technique to obtain and preserve the atrial natriuretic factors (ANFs) which may be useful for eventual studies on the properties of these factors, we performed experiments on rat isolated atrium. 2. The two atria of adult Wistar rats (200-300 g body wt) deprived of food and water for 48 hr, were set up in an organ bath with modified Krebs-Henseleit solution and submitted progressively to increasing tensions of 0.5, 1.5 and 3.0 g. A sample of 2 ml obtained from the bath was treated with acetic acid 1 M and kept at -12 degrees C. Within 2 days the samples were evaluated for the activity of ANFs on isolated rat aortic rings. Aortic rings previously contracted with a submaximal concentration of phenylephrine were slowly relaxed by the samples. 3. Samples from atria submitted to the highest tension shifted the dose-response curve of contraction induced by increasing cumulative doses of phenylephrine to the right. This activity was absent from samples obtained from the solution in which the atria were dissected. This experimental model allows one to obtain and preserve a vascular relaxing factor from atrial myocardium. PMID- 8482516 TI - Characterization of the nipecotic binding to rat brain membranes. AB - 1. The specific binding of [3H]Nip and [3H]GABA to rat brain membranes has been reexamined. 2. Specific binding of [3H]Nip and [3H]GABA was exclusively dependent on sodium ions in a cooperative manner (Hill coefficient 2.2 +/- 0.2 and 2.4 +/- 0.3 for [3H]Nip and [3H]GABA binding, respectively). Potassium, lithium or choline chloride salts were ineffective for replacing NaCl. 3. Maximal binding was observed at 2 degrees C. The association constants were K+1 = 0.033 min-1 microM-1 for [3H]GABA. The dissociation constants obtained by the addition of 1 mM of non-labeled GABA were 0.087 +/- 0.01 min-1 and 0.139 +/- 0.025 min-1 for [3H]Nip and [3H]GABA, respectively. Scatchard curves were in agreement with these constants, KD = 1.6 microM for [3H]GABA and 2.6 microM for [3H]Nip with equal Bmax = 138 pmol per mg protein. 4. The dissociation constants for [3H]Nip bound increased from 0 to 0.035, 0.18 and 0.58 min-1 at 2, 16, 26 and 37 degrees C, respectively, contrary to the hydrophobic derivate of nipecotic acid, NO 328. 5. Pharmacological characterization and regional brain distribution of [3H]Nip and [3H]GABA binding and uptake, suggest that [3H]Nip specifically labels the neuronal GABA uptake system, absent in peripheral tissues. PMID- 8482517 TI - Duration-dependent attenuation of acetylcholine--but not histamine--induced relaxation of the aorta in diabetes mellitus. AB - 1. The relaxations of aortic preparations from 1, 4 and 12 week diabetic rats to acetylcholine and histamine were studied. 2. The relaxation to acetylcholine but not to histamine was significantly attenuated in the 4th and 12th weeks of the disease. In addition, the tissues became less sensitive to acetylcholine but not to histamine with increasing duration of the disease. 3. The results show that there is differential alteration in the responsiveness of the aorta from diabetic rats to both agents. PMID- 8482518 TI - Electrophysiological comparison of the effects of MCI-154 on smooth muscles between mesenteric artery and vein of dogs. AB - 1. Effects of MCI-154, a cardiotonic vasodilator, on smooth muscles were compared in isolated mesenteric artery and vein of dog. 2. MCI-154 depolarized the membrane, and inhibited Ca(2+)- and K(+)-contractions more in the vein than in the artery. 3. Nerve-mediated and noradrenaline-induced contractions, and the excitatory junction potential (e.j.p.) were inhibited by MCI-154 in the vein and potentiated in the artery. 4. Compound action potentials of perivascular nerves and action potentials generated on the e.j.p. were not altered by MCI-154. 5. MCI 154 predominantly dilates venous muscles, and as a result would reduce cardiac outflow and lower systemic blood pressure. PMID- 8482519 TI - Effects of two selective dopaminergic antagonists on ethologically-assessed encounters in male mice. AB - 1. Although it is accepted that dopaminergic antagonists suppress aggressive behaviour, the drugs used have been relatively non-selective or specific to the D2 receptor. 2. The selective D1 antagonist, SCH 23390, makes it possible to evaluate the impact of this receptor on aggressive behaviour. 3. The effects of SCH 23390 and Spiperone (a D2 antagonist) on the aggressive behaviour of mice were assessed employing a "standard opponent" test. 4. Both drugs markedly decreased aggressive behaviour whilst increasing immobility. However, whilst SCH 23390 increased immobility to a small extent, Spiperone, produced a general decline in active behaviours. 5. It appears that the D1 receptor inhibition of aggression is the more specific. PMID- 8482520 TI - Characterization of maximal intravenous dose volumes in the dog (Canis familiaris). AB - 1. Pharmacological evaluation of intravenously administered drugs is frequently limited by the dose volume. Commonly used osmolytes in dosing solutions are isotonic sodium chloride (0.9%) and dextrose (5%). 2. The objective of this study was to determine the maximum volume of an isotonic intravenous (i.v.) solution to be given to conscious dogs. 3. Four dogs (2 male, 2 female), prepared for urine collections and for blood pressure and heart rate determinations, were given saline or dextrose intravenously at infusion rates of 0.3 ml(kg min)-1, 1.0 ml(kg min)-1 or 3.0 ml(kg min)-1 for 60 min; a sham-infusion was also performed. 4. Hematocrit and serum osmolality, BUN, sodium, potassium, chloride, creatinine and glucose, urinary excretion of sodium, potassium, chloride, and urine flow rate, urine osmolality, and renal creatinine and glucose clearances were determined. 5. Intravenous infusion of greater than 1.0 ml(kg min)-1 (60 ml/kg) 0.9% saline was associated with significant hemodilution and tachycardia. 6. Intravenous infusion of greater than 0.3 ml(kg min)-1 (18 ml/kg) 5% dextrose was associated with significant hemodilution, hyponatremia, tachycardia and delayed CNS disturbances associated with hyponatremia. 7. Hence, the limiting volumes of isotonic vehicles that can be administered intravenously to conscious dogs without contributing substantial effects on systemic or renal function are approx. 60 ml/kg 0.9% saline (or an equivalent non-metabolizable osmolyte) and approx. 18 ml/kg 5.0% dextrose (or an equivalent metabolizable osmolyte), administered over 60 min. PMID- 8482521 TI - Characterization of the renal handling of p-aminohippurate (PAH) in the beagle dog (Canis familiaris). AB - 1. The renal clearance of p-aminohippurate (PAH) is the most commonly used method for estimation of renal blood flow in laboratory animals and in humans. 2. This study characterizes the renal handling of PAH in 11 beagle dogs and describes for this species critical parameters for the valid use of the renal PAH clearance technique to estimate renal blood flow. 3. PAH was given as a priming dose plus infusion rates of 0.01-6 mg/kg per min. 4. Steady-state plasma concentrations were achieved within 60 min. 5. Urinary excretion of PAH accounted for > or = 90% of the PAH infused. 6. Plasma PAH concentrations increased linearly with dose. 7. Renal secretion of PAH exceeded filtered PAH at plasma PAH concentrations less than approx. 6 mg%. 8. The TmPAH for renal PAH secretion was approx. 0.4 mg/kg per min. 9. At PAH infusion rates above TmPAH the clearance of PAH decreased and asymptotically approached the value of the GFR. PMID- 8482522 TI - Comparison of actions of endothelium-derived nitric oxide and sodium nitroprusside on mechanical responses evoked in aorta and mesenteric artery of the rabbit. AB - 1. The effects were investigated of endothelium-derived nitric oxide (EDNO; EDRF) and sodium nitroprusside (SNP) on the contraction evoked by noradrenaline (NA) or perivascular nerve stimulation in the presence (+E) or absence (-E) of endothelial cells in the rabbit mesenteric artery and aorta. 2. Acetylcholine (ACh) was more potent in relaxing (+)-tissues of the aorta than those of the mesenteric artery. These relaxing effects of ACh were inhibited under pretreatment with NG-nitro-L-arginine (L-NNA). 3. SNP relaxed the contraction evoked by NA or electric field stimulation in the aorta more than in the mesenteric artery in the presence or absence of endothelium. L-NNA (> 15 microM) consistently enhanced the amplitude of contraction evoked by either NA or electric field stimulation more strongly in (+E)-tissues from the mesenteric artery than in these from the aorta. 4. L-NNA accelerated the relaxing actions of SNP on contractions evoked by NA in (+E)-tissues prepared from the mesenteric artery though this action was less marked in the aorta. 5. Spontaneous release of EDNO is more potent in inhibiting contraction evoked in the mesenteric artery than in the aorta, whereas derived NO and exogenously applied NO are more potent in inhibiting contraction evoked in the aorta than in the mesenteric artery. PMID- 8482523 TI - Effect of trapidil on serum lipid and apolipoprotein levels in patients with ischemic heart disease. AB - 1. Serum total cholesterol (TCH), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein (LDL-C), atherosclerotic index (AI) and apolipoprotein (apo A-I, A-II, B, C-II, C-III and E) levels were investigated in patients with ischemic heart disease before and after medication of trapidil. 2. Twenty-one patients were orally given 100 mg of trapidil, three times daily (300 mg/day). After 8 weeks' administration, serum HDL-C level increased (P < 0.01) and AI decreased (P < 0.02) significantly, whereas TCH, TG and LDL-C levels tended to decrease but not significantly. 3. Among the parameters of apolipoproteins, apo A-I, a main protein of HDL-C, was significantly increased (P < 0.05) by trapidil. 4. These results indicate that trapidil has a beneficial effect on the coronary risk profile as reflected by lipid measurements. PMID- 8482524 TI - Estrogen and antiestrogen non-genomic effect in rat uterus contraction in calcium free solution. AB - 1. The effects of estrogens estradiol (E2, 10(-6)-10(-4) M) and diethylstilbestrol (DES, 10(-6)-10(-4) M) and the antiestrogens nafoxidine (N, 10(-6)-10(-4) M), tamoxifen (T, 10(-6)-6 x 10(-4) M), tamoxifen ethyl bromide (TEB, 10(-4) M) and ICI 164,384 (ICI, 10(-5) M) on tonic contractions induced by oxytocin (2 x 10(-8) M) or vanadate (3 x 10(-4) M) in rat uterus incubated in calcium-free EDTA treated solution have been assayed. 2. E2 and DES relaxed the tonic contraction induced by oxytocin in a dose dependent way (EC50: 1.11 +/- 0.01 x 10(-4) M and 1.5 +/- 0.07 x 10(-5) M). The vanadate-induced contraction only was relaxed with DES (57.62 +/- 2.38% at 10(-3) M). 3. The effect of DES on oxytocin contraction was unmodified by the protein synthesis inhibitor cycloheximide (10 micrograms/ml) and by the cyclooxygenase inhibitor indomethacin (3 x 10(-6) M), but enhanced by the intracellular calcium release inhibitor TMB-8 (10(-5) M). The antiestrogen tamoxifen (3 x 10(-5) M) promotes the relaxing effect of DES. 4. The antiestrogens N, and T, but not ICI, relaxed the oxytocin induced contraction (EC50: 4.51 +/- 0.43 x 10(-5) M and 2.27 +/- 0.05 x 10(-4) M). TEB (10(-4) M) produces a relaxation of 74.5 +/- 2.11%. The vanadate contraction is also relaxed by T (EC50: 6.03 +/- 0.04 x 10(-4) M). 5. The effect of T on oxytocin contraction was unmodified with cycloheximide or TMB-8 but decreased with indomethacin. PMID- 8482525 TI - Studies on the hypotensive mechanisms of NZ-105, a new dihydropyridine derivative, in rats and rabbits. AB - 1. Intravenous administration of NZ-105 caused a slow-onset and long-lasting hypotension in anesthetized SHR. 2. Centrally administered NZ-105 (0.04 mg/kg) slightly decreased blood pressure. 3. The hypotension of NZ-105 (0.1 mg/kg, i.v.) was not affected by atropine, propranolol, diphenhydramine plus cimetidine, aminophylline or indomethacin. 4. In ganglion-blocked rats, NZ-105 (0.003-0.3 mg/kg, i.v.) inhibited the pressor response to several hypertensive agents to a similar degree. 5. In pithed SHR, NZ-105 (0.03 mg/kg, i.v.) showed the same degree of hypotensive action as in non-treated SHR. 6. NZ-105 did not inhibit reflex responses to tilting in conscious rabbits. 7. Thus NZ-105 exerts its hypotensive action through the mechanisms of peripheral origin. PMID- 8482526 TI - Behaviour of leukocyte membrane fluidity in presence of anaesthetic drugs. Comparison between allergic patients and control subjects. AB - 1. In this study we compared the effects of two anaesthetic drugs on the leukocyte membrane fluidity in allergic patients versus control subjects. 2. Fluidity was assessed by means of the fluorescence polarization technique. 3. We report that the treatment of the whole leukocytes with thiopental or pancuronium enhanced membrane fluidity in the allergic group as well as in the control one, but the effect was more pronounced in allergics. 4. This finding suggests a different biophysical behaviour of the leukocyte membrane towards anaesthetic drugs in allergic diseases. 5. This agrees with the hypothesis of the existence of an intrinsic abnormality in allergic cells, expressed as an initial hyperreactive state. PMID- 8482527 TI - The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity. AB - 1. The influences of the purported serotonergic agonist 5-methoxy-N,N dimethyltryptamine (MeODMT) on noradrenaline release and metabolism were investigated in a rat spinal cord release model and a monoamine oxidase (MAO) assay. 2. MeODMT inhibited the basal outflow of tritium from rat spinal cord slices preincubated with [3H]noradrenaline and enhanced the electrically-evoked overflow. 3. Effects on basal outflow were not observed, when monoamine oxidase (MAO) was inhibited by pargyline. Effects on the evoked overflow were not observed in the presence of metitepine or phentolamine. 4. Preferential inhibition by MeODMT of MAO A-type enzyme activity was found in a direct assay. 5. The results provide evidence for two different effects by which MeODMT reinforces noradrenergic neurotransmission in the rat spinal cord: facilitation of stimulation-evoked noradrenaline release and inhibition of noradrenaline metabolism by MAO inhibition. PMID- 8482528 TI - Comparison of alloxan and streptozotocin induced diabetes in rats: differential effects on microsomal drug metabolism. AB - 1. Liver microsomes from alloxan or streptozotocin diabetic rats displayed differential drug metabolizing abilities in vitro. 2. Only streptozotocin liver microsomes exhibited changes in the cytochrome P-450 normal spectral characteristics. 3. Overall testosterone metabolism was significantly increased in streptozotocin diabetic liver microsomes, whereas it was markedly decreased in alloxan diabetes. Mixed function oxidase activity for aminopyrine was similar. 4. Glucuronidation reaction rates towards morphine, oestrone and p-nitrophenol were also markedly distinct in both models as well as after insulin treatment. 5. Results suggest that diabetogenic agents modify sex related isoenzymes of cytochrome P-450 differently and selectively reduce the synthesis of certain UDP glucuronyltransferase forms. PMID- 8482529 TI - The effects of the intestinal glucosidase inhibitory BAY M 1099 (miglitol) on glycemic status of obese-diabetic rats. AB - 1. Groups of lean and obese-diabetic (NIDDM) congenic male SHR/Nutl parallel-cp rats were fed a nutritionally adequate, high carbohydrate diet ad libitum with or without the alpha-glucosidase inhibitor miglitol (150 mg/kg diet) from 8 until 15 weeks of age, and key glycemic parameters were monitored throughout the study. 2. Miglitol treatment resulted in clinical improvement toward normal in percent glycosylated hemoglobin, glycemic and insulinogenic responses to an oral glucose tolerance, and in liver glucokinase activity, in concert with modest decreases in weight gain in obese rats. 3. These observations are consistent with improved insulin sensitivity in peripheral tissues following miglitol treatment, and indicate that this drug may be a useful adjunct to diet in the treatment of obesity, NIDDM, and possibly other disorders of carbohydrate metabolism. PMID- 8482530 TI - Analysis of dinucleotide frequency and codon usage in the phylum Apicomplexa. AB - Dinucleotide frequency (DiF) and codon usage (cu) were analysed in gene sequences from four parasitic protozoa, Babesia bovis, Theileria parva, Toxoplasma gondii and Eimeria tenella, of the phylum Apicomplexa. In keeping with the 'genome hypothesis', cu was found to be non-random and species specific in these organisms, although cu among members of the same subclass was found to be very similar. Several low-usage (lu) codons were identified, and the usage of lu codons appears to be related to the taxonomic position of the organisms under study. A comparison of the observed/expected DiF ratios obtained from gene coding regions revealed a low frequency of the TA and CG dinucleotides in all organisms studied. A comparison of these DiF ratios with those found in rRNA-encoding genes and in introns, showed that in the parasites, B. bovis and Th. parva (representing the piroplasms), the low frequency of dinucleotides appeared to be the result of coding pressure alone. In T. gondii and E. tenella (representing the coccidia), however, coding pressure could not completely explain differences in DiF. PMID- 8482531 TI - Adh and Adh-dup sequences of Drosophila lebanonensis and D. immigrans: interspecies comparisons. AB - We have cloned and sequenced the Adh genomic region of Drosophila lebanonensis (subgenus Scaptodrosophila) and D. immigrans (subgenus Drosophila). This region, which contains Adh, encoding the alcohol dehydrogenase enzyme, and Adh-dup (duplicate of Adh), has been compared with the same fragment from D. subobscura (subgenus Sophophora). Even though the flanking regions and introns of both genes have been affected by high substitution rates, the consensus sequences have been clearly identified. Although the overall homology of the coding regions was 76 78% among the species compared, there were differences in the exon distribution of the nucleotide substitutions when Adh or Adh-dup were compared, thus showing that these two genes differ in their evolutionary pattern. PMID- 8482532 TI - Induction of the murine class-II antigen-associated invariant chain by TNF-alpha is controlled by an NF-kappa B-like element. AB - The murine class-II antigen-associated invariant chain (Ii) is a glycoprotein whose synthesis is co-regulated with the major histocompatibility class-II antigens. The Ii mRNA is inducible by tumor necrosis factor-alpha (TNF-alpha). An NF-kappa B protein-binding site (NBS), located in the Ii promoter at bp -121 to 111, confers TNF-alpha inducibility on chimeric reporter constructs expressing the human growth hormone-encoding gene. A distal NF-kappa B-like protein-binding site (NBLS) located at bp -167 to -157 is not required for TNF-alpha inducibility, and deletion of this distal NBLS results in increased constitutive, as well as TNF-alpha-induced, expression of the reporter gene. The NBS is well protected during DNase I footprinting assays and specifically binds proteins in electrophoretic mobility shift assays. A distinct protein-DNA complex is observed when nuclear extracts from TNF-alpha-treated L-cells are used; this complex is not seen in extracts from untreated cells. PMID- 8482533 TI - Structure of the gene encoding the mouse 47-kDa heat-shock protein (HSP47). AB - HSP47, a 47-kDa heat-shock protein (HSP), is a member of a group of HSPs with the unique characteristics of collagen binding as well as transformation sensitivity. The protein belongs to the serpin (serine protease inhibitor) superfamily as determined from its amino acid sequence homology. We have isolated and characterized the mouse HSP47 including about 1 kb of the 5'-flanking region. This gene spans about 7.8 kb, consisting of six exons separated by five introns. This exon-intron structure is different from other serpin family proteins. Southern blot analysis revealed the existence of a single copy of HSP47. The promoter region contains a TATA box, four Sp1-binding sites and one AP-1-binding site. A complete heat-shock element (HSE) was found between nucleotides (nt) -61 and -79. Furthermore, the heat inducibility was reproduced by transfecting mouse BALB/3T3 cells with a plasmid carrying cat under the control of the HSE containing fragment (nt -197 and +38) of HSP47. Computer analysis of the promoter region did not show marked homology to other vertebrate promoters. PMID- 8482534 TI - DNA-binding proteins and their cis-acting sites controlling hormonal induction of a mouse beta-casein::CAT fusion protein in mammary epithelial cells. AB - Transcription of the mouse beta-casein (beta CAS)-encoding gene (casB) is regulated by the synergistic actions of insulin, glucocorticoid and prolactin in the mammary gland (MG). To delineate its regulatory sequence(s), we examined the hormonal inducibility of various chimeric constructs containing the promoter sequence of casB and the cat reporter gene in primary MG epithelial cells. A DNA fragment from bp -258 to +7 of casB was sufficient for the hormonal induction. Using a series of 5'- and internal deletions of the casB promoter region, at least three DNA elements were found to be necessary for full induction. These were located at bp positions -258 to -180, -154 to -136, and -98 to -62. DNase I footprinting analysis with a partially purified extract from lactating MG cells detected at least seven protected sequences, I(-242 to -219), II(-213 to -202), III(-151 to -139), IV(-125 to -110), V(-98 to -90), VI(-79 to -70) and VII(-59 to -45). Regions I/II, III and V/VI were included in the three DNA elements required for the hormonal induction, and the IV region corresponded to the MG consensus sequences of several milk protein-encoding genes. Competition gel retardation assays using nuclear extracts of lactating mouse MG revealed the presence of specific binding proteins for regions I, II, IV and VI, as well as specific protein(s) binding to both regions III and V. The binding activities of these proteins, except that associated with region IV, were increased from the virgin to lactating periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482535 TI - Characterization of the 5' flanking region of the gene encoding rat liver glycogen phosphorylase. AB - A genomic region encompassing 800 bp of the promoter-regulatory region and exon 1 of the gene (LGP) encoding rat liver glycogen phosphorylase has been isolated and characterized. Transcripts of the LGP gene initiate predominantly within an 8-bp region 48-bp upstream from the start codon. Additional transcripts were detected that initiate as far as 95 bp upstream from the start codon. To identify cis acting sequences involved in regulating transcription, HepG2 cells were transfected with vectors containing serial deletions of the promoter-regulatory region of LGP ligated to the cat reporter gene. Two upstream regions were found to enhance transcription. One of these regions contains an alternating purine pyrimidine sequence. LGP, which lacks a consensus TATA sequence, is like TATA less and CAAT-less housekeeping genes in that it contains G + C-rich domains upstream from multiple transcription start points. Nuclear proteins from adult rat tissues bound in a tissue-specific fashion to one of these G + C-rich regions. PMID- 8482536 TI - Sequence and single-base polymorphisms of the bovine alpha-lactalbumin 5' flanking region. AB - The alpha-lactalbumin (alpha LA)-encoding gene is a potential quantitative trait locus in dairy animals. In cattle, the production of alpha LA is tightly coupled to the onset of lactation and it serves as a regulatory subunit of the enzyme responsible for lactose synthesis. Lactose is the major osmole controlling water movement in the mammary gland. To better understand the control of bovine alpha LA expression, the 5'-flanking region of a Holstein alpha LA gene was cloned and sequenced. The sequenced clone contains 1952 bp of 5'-flanking region and 66-bp of the protein-coding region. Three single-bp polymorphisms were identified within this region. These polymorphisms occur at positions +15, +21 and +54 relative to the mRNA transcription start point (tsp). The +15 and +21 variations occur in the region encoding the 5'-untranslated region of the mRNA-coding sequence. The +54 polymorphism is a silent mutation in the SP-coding region of the gene. A polymerase chain reaction (PCR, Cetus)-based screening method has been employed to analyze the genotype of cattle at the +15 position. A total of 501 randomly selected cattle from seven breeds were screened for this allele. Of these animals, only the Holstein breed of cattle was found to contain the +15 variation and it occurs at a gene frequency of 32%. Sequence comparisons were conducted between the 5'-flanking regions of the bovine-milk-protein encoding genes, alpha LA, beta-casein and alpha S1-casein, which are coordinately expressed. Regions of similarity extending to 350 bp in length were observed between these sequences. PMID- 8482537 TI - Cloning of human and rat cDNAs encoding the mitochondrial single-stranded DNA binding protein (SSB). AB - We have retro-transcribed and amplified by PCR the full-length cDNAs specifying the rat and human precursors of the single-stranded mitochondrial DNA (mtDNA) binding protein (mtSSB). Each deduced sequence is composed of a 16-amino-acid (aa) N-terminal basic pre-sequence and a mature protein (132 aa in humans and 135 aa in the rat). The mature proteins are highly conserved among themselves and with the mtSSB from Xenopus laevis (Xl). Moreover, three regions of the protein are similar to corresponding domains of the SSB of Escherichia coli and to the E. coli F-sex factor SSB, indicating the existence of a broad class of DNA-binding proteins with structural and functional similarities both in prokaryotes and in prokaryote-derived organelles of higher organisms. PMID- 8482538 TI - Human L7a ribosomal protein: sequence, structural organization, and expression of a functional gene. AB - A cDNA coding for the human L7a ribosomal protein (r-protein) was used to isolate the corresponding gene by screening two human genomic libraries constructed in bacteriophage lambda and in a cosmid vector. One of the cosmid clones isolated, cos1.1, contains the whole L7 alpha gene, composed of eight exons and seven introns spanning 3226 bp. As in other mammalian housekeeping genes, the promoter and the first exon of the L7 alpha reside within a CpG-rich island. Furthermore, similar to the other higher eukaryote r-protein-encoding genes characterized so far, the human L7 alpha gene has a C as the major transcriptional start point localized in a pyrimidine-rich region and lacks a canonical TATA sequence. We show that 130 bp of the human L7 alpha gene 5'-flanking region represent the minimal element required to promote its transcription. This element is strikingly conserved between the mouse and human L7 alpha genes. Finally, a comparison of the human L7 alpha gene coding sequence and the predicted amino acid (aa) sequence with the sequences of mouse L7a, rat L7a, and the homologous yeast L4 shows that the aa sequence has been highly conserved during evolution. PMID- 8482539 TI - Cloning and structural organization of a xylanase-encoding gene from penicillium chrysogenum. AB - The filamentous fungus, Penicillium chrysogenum, is able to grow on xylan as a sole carbon source. Under these conditions, high levels of a xylanase (XYLP) are secreted into the medium. After purification and characterization of this enzyme, we have isolated both the encoding cDNA and the genomic sequence by using oligodeoxyribonucleotides derived from partial amino acid (aa) sequences of the purified enzyme. The gene is approximately 1.6 kb in length, and comparison of the nucleotide (nt) sequence of the genomic and the cDNA clone revealed the presence of ten exons and nine introns. All intron/exon splice junctions exactly follow the GT/AG rule, except for the seventh intron which shows atypical AT/AC splice sites. The immediate 5'-flanking region of the first exon contains one putative CCAAT consensus sequence and a perfect TATA box. Primer extension analysis revealed two transcription start points located 38 and 34 nt upstream from the ATG start codon. A sequence of 23 aa representing a typical signal peptide is present at the N terminus of the deduced aa sequence. Northern blot analysis of total cellular RNA indicated that xylP encodes a 1.3-kb transcript which is induced by xylan. The aa sequence of XYLP shows considerable homology to high-M(r) acidic xylanases (Xln) and cellulases from different bacteria, yeasts and fungi. PMID- 8482540 TI - Structure of the Paramecium caudatum gene encoding the B-type of the major hemoglobin component. AB - We have found the gene (Hb) encoding the B-type of the major hemoglobin (Hb) component in the ciliated protist, Paramecium caudatum, stock K33 of syngen 3. Gene Hb, which encodes a protein consisting of 116 amino acids (aa), had the same sequence as the A-type Hb in this species, with the exception of 10 nucleotides (nt) reflecting 5 single-aa differences. The coding region was interrupted at the position between codons 62 and 63 by one short intron, which was comparable with the second intron of plant Hb in position, phase and nt sequence. The maximum alignment of the P. caudatum Hb aa sequence with the other globin sequences from prokaryotes and lower eukaryotes indicates that these globins can be classified into two groups: one consists of protist and cyanobacterial globins of about 120 aa, and the other consists of fungal and other bacterial globins of about 150 aa having a significant homology with higher eukaryotic Hbs. These proteins share more than 25% homology with one another in each group. Our finding of the P. caudatum Hb intron corresponding to the second intron of plant Hb suggests that all of the globin-encoding genes have a common origin, and that at least two groups had already existed in the globin-encoding gene before prokaryote eukaryote radiation. PMID- 8482541 TI - Expression of the gene encoding secreted placental alkaline phosphatase (SEAP) by a nondefective adenovirus vector. AB - A nondefective recombinant human adenovirus 5 (Ad5) carrying the SEAP gene, encoding human secreted placental alkaline phosphatase, in the E3 region of the Ad5 genome was obtained. The expression of SEAP at the early and late stages of Ad5 infection was demonstrated in permissive and semi-permissive cell cultures. The amount of SEAP in the culture medium of the 293 cells was 13.6% of the total protein. PMID- 8482542 TI - Cloning of a cDNA encoding a DNA-binding protein TAXREB302 that is specific for the tax-responsive enhancer of HTLV-I. AB - The transcriptional activator, Tax, of human T-cell leukemia virus (HTLV-I) has been considered to interact with cellular proteins to act on target enhancer motifs. Using oligodeoxyribonucleotides containing the tax-responsive element (TAXRE) of the HTLV-I enhancer, we have cloned multiple cDNAs coding for TAXRE binding proteins (TAXREB), and determined the cDNA and the deduced 200-amino-acid sequences for TAXREB302. The recombinant protein binds to the enhancer DNA by specific interaction to the CRE-like sequence. A single 1.8-kb species of mRNA was detected in cultured cells, as well as in normal human tissues, especially brain and skeletal muscle. The 22-kDa native protein was detected in the cultured cell lysate by immunoblotting analysis. TAXREB302 does not have structural features common to the CRE-binding protein or activating transcription factor (CREB/ATF) family, but has homology to chicken erythroid transcription factor (Eryf1 or GATA-1), suggesting a possible protein-protein interaction. PMID- 8482543 TI - Cloning of a cDNA encoding sheep calcitonin from a thyroid C-cell library. AB - A sheep thyroid C-cell cDNA library constructed in lambda ZAPII was screened with a probe specific for the human calcitonin (CT)-encoding gene (CT). Plaque lifts from a total of 6 x 10(4) recombinant plaques identified six overlapping cDNA clones, one of which was an 806-bp cDNA representing an almost full-length copy of the sheep CT mRNA. The nucleotide (nt) sequence consists of a 71-bp 5' flanking sequence, a protein-coding region of 429 bp with a coding potential for a 143-amino-acid (aa) protein with a deduced M(r) of 15,888 and a 306-bp 3' untranslated region. Northern blot analysis of sheep thyroid tissue revealed two major mRNAs with sizes of 0.9 and 0.65 kb. The sheep CT cDNA shows 71% similarity at the nt level to human CT and 58% identity at the predicted aa level. PMID- 8482544 TI - Consecutive inactivation of both alleles of the gb110 gene has no effect on the proliferation and differentiation of mouse embryonic stem cells. AB - The gene gb110 was originally identified by provirus integration in the Mov10 mouse strain and encodes a 110-kDa protein with potential GTP-binding activity. The gene is evolutionarily conserved, and its expression is controlled in a developmentally and cell-cycle-specific manner, suggesting that it has an important function in differentiation and development. As a first step in studying the functional role of gb110, embryonal stem (ES) cell lines were derived in which both gb110 alleles were inactivated by consecutive gene targeting via homologous recombination. The first allele was interrupted by integration of a neomycin resistance-encoding gene (neo) and, subsequently, the second allele by integration of a hygromycin B resistance-encoding gene (hyg). Selection for homologous recombination was achieved by using promoter and AUG codon-deficient hyg or neo whose expression was dependent on integration into the host genome next to the transcriptional and translational start signals. The efficiency of gb110 gene targeting was very high, with 85-100% of all drug resistant colonies having undergone homologous recombination. ES cells lacking a functional gb110 were indistinguishable from the wild-type ES cells, indicating that this gene is not required for normal ES cell proliferation and differentiation in vitro. PMID- 8482545 TI - Structure of the gene encoding rat neutrophil chemo-attractant Gro. AB - A cloned rat gro gene encoding the neutrophil chemo-attractant Gro was isolated from a lambda Charon4A rat genomic library, and the nucleotide (nt) sequence of a 2500-bp fragment encompassing the coding region and 3'- and 5'-flanking regions was determined. The gene consisted of four exons separated by three introns. The transcription start point was determined by primer-extension analysis and found to be a G located 72 nt upstream from the start codon. The 5'-flanking region of the gene contained a 'TATA'-like structure and an NF-kappa B-binding sequence. PMID- 8482546 TI - Sequence of a cDNA encoding bovine apolipoprotein H. AB - The nucleotide sequence of the ApoH cDNA encoding the bovine apolipoprotein H (ApoH) has been determined. The deduced protein, which contains a 19-amino-acid (aa) signal peptide and the 326-aa mature ApoH, shows 89% and 86% homology with human and rat ApoH, respectively. PMID- 8482547 TI - Sequence of human GAS3/PMP22 full-length cDNA. AB - We have cloned the human growth arrest-specific gene GAS3 cDNA that encodes a transmembrane glycoprotein, the peripheral myelin protein 22 (PMP22). GAS3/PMP22 is implicated in Charcot-Marie-Tooth disease type 1A, an inherited peripheral neuropathy. PMID- 8482548 TI - The deduced amino acid sequence of human carbonic anhydrase-related protein (CARP) is 98% identical to the mouse homologue. AB - A recently reported mRNA, encoding 'carbonic anhydrase-related polypeptide' (CARP) from the Purkinje cells of mouse cerebellum, was shown to have a 30-40% deduced amino acid sequence identity with the carbonic anhydrases (CA) of mammals. In order to compare the mouse and human CARP sequences, we used the polymerase chain reaction (PCR) to amplify human CARP sequences from several cDNA libraries (salivary gland, testis and placenta). The sequence has an 89.3% sequence identity with mouse CARP at the nucleotide level and 97.9% at the amino acid level. This extremely high evolutionary conservation suggests an important function for the CARP gene product. PMID- 8482549 TI - The alternative 5'-end of the Drosophila melanogaster epidermal growth factor receptor cDNA (DER) is part of the D14-3-3 cDNA. AB - A portion of the cDNA reported as a novel cDNA encoding the Drosophila melanogaster homolog of the bovine 14-3-3 protein by Swanson and Ganguly [Gene 113 (1992) 183-190] already exists in the database. It was originally reported as an alternative 5' end of the D. melanogaster homolog of the epidermal growth factor receptor (DER). Schejter and Shilo [Cell 56 (1989) 1093-1164] later reported that this finding was due to a cloning artifact that joined the 14-3-3 cDNA onto the DER cDNA. PMID- 8482550 TI - Drosophila melanogaster poly(A)-binding protein: cDNA cloning reveals an unusually long 3'-untranslated region of the mRNA, also present in other eukaryotic species. PMID- 8482551 TI - CA125 measurement in epithelial ovarian cancer: a 10-year anniversary of clinical investigation. PMID- 8482552 TI - Vaginal squamous cell carcinoma with sarcomatoid spindle cell features. AB - A vaginal squamous cell carcinoma with prominent sarcomatoid spindle cell features found in a 25-year-old female is presented. The exclusively spindle shaped growth pattern of the neoplastic cells in the initial biopsy led to the diagnostic impression of a sarcoma. This in turn has resulted in an attempt at completely resecting the tumor. The 5.2 x 3.5-cm resected lesion, however, blended peripherally with a poorly differentiated squamous cell carcinoma. Moreover, the sarcomatoid component reacted with vimentin and cytokeratin, and tonofilaments and desmosomes were seen by electron microscopy. This apparently unique case indicates the need for obtaining representative tissue samples for providing an appropriate diagnosis prior to definitive therapy for vaginal squamous cell carcinoma. The primary treatment for large stage I squamous cell lesions of the vagina is radiotherapy, whereas an equally large sarcoma is best treated by wide local excision alone. PMID- 8482553 TI - Beta-core fragment of human chorionic gonadotropin in cervical intraepithelial neoplasia (CIN). AB - A low molecular weight glycoprotein immunologically identical with the beta-core fragment of hCG (beta C-hCG) has been described in invasive tumors of the genital tract, particularly carcinoma of the cervix. A previous report has also suggested increased urinary concentrations in subjects with cervical intraepithelial neoplasia (CIN). This prospective study of 107 patients with CIN was conducted to determine concentrations of beta C-hCG in the urine compared to a reference population without CIN. All subjects underwent a cervical smear and colposcopy, with biopsy when indicated. Between 11 and 18% of patients had urinary concentrations of beta C-hCG greater than the upper limit of the reference group and these results were confirmed when corrected for urinary creatinine concentration. A substantial number of subjects (19%) also had a positive result in a C-terminal immunoassay. It is concluded that preinvasive carcinoma of the cervix may secrete hCG or beta C-hCG in the earliest stages although measurement of beta C-hCG is unlikely to prove to be a valuable diagnostic marker in CIN. PMID- 8482554 TI - Stage I cervical adenocarcinoma: prognostic evaluation of surgically treated patients. AB - In order to evaluate clinicopathologic determinants of recurrence in adenocarcinoma of the uterine cervix, a detailed retrospective chart review and complete pathology analysis were performed for 79 patients who had been treated by Type III radical hysterectomy between 1975 and 1988. All patients had clinical stage I disease; 77 had cervical diameters of 4 cm or less. Eleven patients (14%) developed recurrent disease with a median time to recurrence of 14 months (range, 7-51). Recurrence location was central in 5 patients, pelvic wall in 2, and distant in 4. Seven patients died of disease. Five-year actuarial survival was 89%. None of the clinical features examined as possible prognostic factors was predictive of recurrence, including patient age (P = 0.91), cervical diameter (P = 0.30), presence of pain (P = 0.53), presence of abnormal bleeding (P = 0.19), and history of oral contraceptive use (P = 0.58). However, univariate analysis showed lymph node spread (P = 0.008), lymph-vascular space invasion (P = 0.05), and increasing grade (P = 0.05) to be significant predictors of recurrence. Lymph vascular space invasion remained significant when patients with positive nodes were excluded (P = 0.026). Depth of invasion > 3 mm was associated with greater recurrence risk than depth < or = 3 mm (P = 0.01). Number of mitoses (P = 0.10) was not significant. Multivariate analysis selected nodal positivity as the major prognostic parameter (P = 0.04). Further studies are needed to more clearly define the role of lymph-vascular space invasion, as an elevated risk ratio of 1.6 suggests an increased risk for recurrence. Patients whose pretreatment biopsies demonstrate obvious lymph-vascular space invasion might be considered for alternate treatment. PMID- 8482555 TI - Laparoscopic paraaortic node sampling in gynecologic oncology: a preliminary experience. AB - Because of the poor accuracy of nonsurgical methods in the detection of occult paraaortic lymph node metastasis, and because of the cost and discomfort of surgical staging, the feasibility of selective or elective paraaortic lymphadenectomy has been investigated in a preliminary series of four cases. Selective sampling of the lower paraaortic nodes in two cases of cervical carcinoma and of the infrarenal paraaortic nodes in two cases of early ovarian carcinomas were successfully completed by laparoscopy. The potential application of this new technique are discussed. PMID- 8482556 TI - Is serum CA 125 at the time of relapse a prognostic indicator for further survival prognosis in patients with ovarian cancer? AB - The prognostic significance of serum CA 125 level before treatment of relapse for invasive epithelial ovarian cancer has been evaluated in 135 patients. At time of relapse, serum CA 125 level was higher than 35 U/ml in 110 (82%) patients. Those with serum CA 125 level of 35 U/ml or less at relapse had a better prognosis than those with higher values. Among patients with serum CA 125 level higher than 35 U/ml no difference in survival was observed. By multivariate analysis the independent prognostic factors for survival were histologic type (P < 0.0001) and serum CA 125 level (P < 0.01). Randomized trials are needed to further evaluate whether early detection of disease relapse because of serial serum CA 125 measurements does have prognostic significance. PMID- 8482557 TI - A prospective randomized comparison of 6 and 12 cycles of cyclophosphamide, adriamycin, and cisplatin in advanced epithelial ovarian cancer: a Danish Ovarian Study Group trial (DACOVA). AB - Two hundred-two patients with FIGO stages III and IV epithelial ovarian cancer were randomized to 6 or 12 cycles of cyclophosphamide, Adriamycin, and cisplatin (CAP). Patients in complete clinical response underwent a second-look laparotomy, 1 month after cessation of chemotherapy. Patients randomized to 6 cycles and found to be in partial remission at second-look were to receive a further 6 cycles of CAP. Rate of complete pathological response was 23% for 6 cycles of CAP and 25% for 12 cycles; the median survival was 23 months for 6 cycles and 27 months for 12 cycles, and 3-year survival was 29% for 6 cycles and 35% for 12 cycles. None of these differences were statistically significant. Fifty-four patients randomized to 6 cycles were found to be in partial surgical remission at second-look laparotomy, and 24 of these patients agreed to a further 6 cycles and a third-look laparotomy. Six of these 24 patients had a complete pathological response at third-look, improving the complete response rate to 28% in those originally randomized to 6 cycles. However, 3 of these patients all had macroscopic tumors removed at second-look, and two had microscopic disease at second-look. Among patients achieving complete response mean cumulative doses in the CAP 6 cycle group were approximately 50% of those in the CAP 12 cycle group. However, when all patients were considered, this difference was only approximately 15% owing the continuation of chemotherapy in the partial responders of the 6 cycle group and early stopping for chemotherapy in the CAP 12 cycle group due to toxicity or progression. Patients in complete pathological response also showed similar survivals for 6 and 12 cycles. In conclusion, the study did not show a correlation between mean cumulative doses and complete pathological response and survival. PMID- 8482558 TI - Cerebral metastases secondary to ovarian cancer: still an unusual event. AB - An incidence of cerebral metastases secondary to epithelial ovarian cancer as high as 11.6% has been reported in small series and related to the prolonged survival of ovarian cancer patients treated with platinum compounds (Hardy, J. R., and Harvey, V. J. Gynecol. Oncol. 33, 296-300, 1989). A review of the histories of 413 ovarian cancer patients, treated from 1981 to 1989 with platinum based combination chemotherapy according to the protocols of the Gruppo Oncologico Nord Ovest (GONO) (North West Oncology Group), showed that only 9 patients (2.2%) developed clinical evidence of cerebral metastases. Six of 9 patients had FIGO Stage IIIc disease and 1 each with FIGO Stages Ic, IIc, and IV. All these patients had received cisplatin or carboplatin-based combination chemotherapy. Clinical response to initial cytotoxic therapy was as follows: complete response, 3 patients; partial response, 4 patients; stable disease, 1 patient; progressive disease, 1 patient. Cerebral metastases occurred at a median of 19 months (range 3-36) from diagnosis and median survival of patients with central nervous system (CNS) metastasis was 26 months (range 10-81) from diagnosis of primary disease and 8 months (range 1-45) from diagnosis of CNS involvement. The incidence of CNS metastases in our series is similar to that reported in the past and significantly lower than figures reported by the above mentioned paper. On the basis of our data we do not agree with Hardy and Harvey about the relationship possibly existing between prolonged survival and incidence of CNS metastases and, particularly, about the need for prophylactic cranial irradiation. PMID- 8482559 TI - Mesonephric remnant hyperplasia of the cervix: a clinicopathologic analysis of 14 cases. AB - Lesions derived from mesonephric remnants in the uterine cervix are rare. We describe 14 patients with benign, hyperplastic mesonephric remnant lesions. The patients ranged in age from 31 to 81 years (mean, 47). Four were postmenopausal. The lesions were incidental findings in all but 2 of the patients and frequently had been submitted for consultative pathologic opinion. Two patients did, however, present with symptoms (vaginal bleeding) likely attributable to their lesions and 1 of them had a cervical abnormality on clinical examination. Microscopically, the lesions were composed of lobular or diffuse proliferations of small, round mesonephric tubules which were frequently deep within the cervical wall and often extended to the surface of the cervix. Five of the patients had a referring diagnosis of probable or definite cervical adenocarcinoma due to the infiltrative appearance of the lesions. No mesonephric carcinomas were encountered. Hyperplastic lesions of mesonephric remnants are usually benign, incidental findings but may on occasion be associated with clinical symptomatology and are a potential source of diagnostic confusion for the pathologist. PMID- 8482560 TI - Phase II study of ifosfamide and mesna in nonsquamous carcinoma of the cervix: a Gynecologic Oncology Group study. AB - A phase II trial of ifosfamide (IFX) and mesna was conducted by the GOG in patients with recurrent or advanced nonsquamous carcinoma of the cervix. A starting dose of 1.5 g/m2 IFX iv daily for 5 days and 300 mg/m2 mesna iv every 4 hr with three doses daily after IFX were given. In patients who had received prior radiotherapy or chemotherapy, the starting dose of IFX was reduced to 1.2 g/m2. Forty-six patients were entered, and 41 are evaluable for toxicity. Forty patients are evaluable for response. Age range was 30-72 yr. GOG performance status was 0-1 for all but 2 patients. Fifteen patients (37.5%) developed GOG grade 3 or 4 granulocytopenia, and 1 developed grade 4 thrombocytopenia. One patient developed transient renal insufficiency. There was one complete response and five partial responses (12.5%) for a response rate of 15.0%. Median response duration was 4.2 months (range, 1.7-22.6 months). Three responses were seen in areas with pelvic disease only. Three responses were observed in extrapelvic sites. IFX possesses activity which compares favorably with that of other agents in this disease. PMID- 8482561 TI - Relationship between paraaortic lymph node involvement and intraperitoneal spread in patients with ovarian cancer--a multivariate analysis. AB - In 125 patients with epithelial ovarian cancer (FIGO stages I-IV), 32 (26%) had paraaortic lymph node (PAN) metastases. The estimated 5-year survival rate of PAN negative patients was 71%, while that of PAN-positive patients was 17% (P < 0.0001). Positive rates of PAN metastasis at each stage level, based only on intraperitoneal spread of the disease, were 2% for stage I, 9% for stage II, 43% for stage III, and 87% for stage IV. According to univariate analysis, histological grade, and all disease site parameters examined, such as subdiaphragmatic surface, liver and spleen capsule, intestines and mesentery, omentum, pelvic peritoneum, sigmoid colon and rectum, uterus and tubes, and peritoneal cytology, showed a statistically significant correlation to the presence of PAN metastasis. Multivariate analysis using the logistic regression model revealed that the omental involvement, uterine and tubal involvement, and histological grade were independently correlated with PAN metastasis. The relative risk of PAN metastasis in the patients with these three factors is 18.5 times higher than that in patients without these factors. The present data suggested that, for the disease with omental and/or uterine and tubal involvement, surgical evaluation of PAN is mandatory in order to perform correct FIGO staging. PMID- 8482562 TI - Type II estrogen-binding sites in human ovarian cancer: correlation with estrogen, progesterone, and epidermal growth factor receptor. AB - Type II estrogen-binding sites (Type II EBS) and the recently identified bioflavonoid-like ligand methyl-p-hydroxyphenyllactate may be regarded as a growth regulatory system active on both normal and neoplastic tissues. It has been reported that, in addition to estrogen and progesterone receptors, primary ovarian cancers also express Type II estrogen binding sites. These sites are able to bind estrogenic compounds and also some naturally occurring flavonoids such as quercetin. In this study we report the presence of cytosolic Type II EBS in a series of 10 normal ovaries, 42 primary ovarian tumors, and 14 metastatic deposits. Scattered levels of Type II EBS were found in normal ovarian tissues (median, 1603 fM/mg protein, range, 271-4943). In primary ovarian tumors and in omental metastases median levels of Type II EBS were 835 fM/mg protein (range, 134-4875) and 758 fM/mg protein (range, 204-2007), respectively. Although Type II EBS tend to be higher in normal than in malignant tissues the difference was not statistically significant. No correlation was found between Type II EBS levels and the common clinicopathological characteristics of the tumors. Moreover there was no relation between Type II EBS and estrogen and epidermal growth factor receptors. A significative inverse correlation with progesterone receptor levels was observed. The presence of Type II EBS in ovarian cancer could be of clinical importance since it has been demonstrated that bioflavonoids, through the interaction with Type II EBS, may exert a growth inhibitory activity both alone or in combination with chemotherapeutic agents on ovarian cancer cell lines and primary tumors. PMID- 8482563 TI - Serum CA 125 level allows early identification of nonresponders during induction chemotherapy. AB - CA 125 was measured during induction chemotherapy in 119 patients with advanced epithelial ovarian cancer who had residual disease after primary surgery in order to determine whether patients with poor response to further treatment could be identified during early chemotherapy. All patients had a prechemotherapy serum CA 125 level higher than 35 U/ml. Blood samples were further obtained 4 weeks after the first, second, and third course. Four weeks after the second course of chemotherapy, all 20 patients with PCR, or microscopic disease at second-look, all 17 who achieved complete clinical remission, and 36 of 40 who achieved partial remission had serum CA 125 of 65 U/ml or less or had a decrease of 50% or more of the prechemotherapy level. Survival analysis showed that patients with a serum CA 125 level of 65 U/ml or less 4 weeks after the second course of chemotherapy had the best prognosis. In patients with a serum CA 125 level higher 65 U/ml at that time, a decrease of 50% or more of the prechemotherapy level indicated a prognosis better than that with a lesser decrease. The combined criteria for serum CA 125 (level > 65 U/ml 4 weeks after the second course and a decrease < 50% of the prechemotherapy level) allowed for identification of a real high-risk group with a median survival of 8.9 months and was identified by Cox regression multivariate analysis as the most powerful indicator for survival (P < 0.0001). PMID- 8482564 TI - Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides. AB - In previous work, we saw that interleukin-6 (IL-6), a multifunctional cytokine, is produced by epithelial ovarian cancer cells and that ovarian cancer cells express the IL-6 receptor. Here, we examined the possibility that IL-6 acts as an autocrine growth factor for ovarian cancer cells. Inhibition of IL-6 gene expression by exposure to IL-6 antisense oligonucleotides resulted in greatly decreased cellular proliferation. Exposure of ovarian cancer cell lines (CAOV-3, OVCAR-3, and OC-436), to 1-5 microM of a 15-base single-stranded antisense IL-6 oligodeoxynucleotide, specific for a sequence in the second coding exon of the IL 6 gene, resulted in decreased IL-6 production and a > 80-85% inhibition of cellular proliferation. However, the addition of exogenous IL-6 failed to restore the proliferation of the antisense-treated cells. Antibodies to IL-6 did not consistently inhibit cell growth nor did rIL-6 enhance precursor frequency in a limiting dilution analysis. These results suggest that IL-6 does not directly induce the proliferation of ovarian cancer cells although endogenous IL-6 production is needed for optimal cell growth. As the majority of epithelial ovarian cancers produce IL-6, the direct specific inhibition of IL-6 gene expression is of potential therapeutic value. PMID- 8482565 TI - Monoclonal antibodies MA54 and MA61 as potential reagents in the prognosis of patients with ovarian cancer. AB - Monoclonal antibodies (moABs) MA54 and MA61 directed to the O-linked NeuAc alpha 2-6GalNAc epitope were generated by immunization with culture supernatants of lung adenocarcinoma cells. We have examined the correlation between the prognosis of patients (overall survival and progression-free survival) and circulating serum levels of CA54/61 antigen by comparison with CA125 in patients with epithelial ovarian cancer. Circulating serum CA54/61 antigen levels were determined by sandwich enzyme immunoassay kits. Serum antigen levels were elevated in 44.4% of the patients. Survival at 3 years for ovarian cancer patients with CA54/61-negative (serum CA54/61 levels < 15.2 U/ml) versus CA54/61 positive (CA54/61 > or = 15.2 U/ml) tumors was 64% versus 25% (P < 0.05). In contrast, there is no significant difference in the prognosis of patients based upon positive or negative CA125 antigen values (51% vs 67%). The overall survival rate was worse in patients with CA54/61-positive sera, indicating that positive CA54/61 levels in serum is an independent predictor of poor prognosis in ovarian cancer. In addition, CA54/61 status has been shown to be associated with early relapse of this malignancy. PMID- 8482566 TI - Treatment of advanced ovarian carcinoma in the elderly. AB - This study retrospectively analyzes the treatment of advanced ovarian cancer (Stages III and IV) in elderly patients (> or = 65) compared to that in younger patients (< 65). The purpose of this study was to identify possible treatment bias toward the elderly and to statistically analyze the nature of these differences. Seventy patients were evaluated of which 29 were identified as elderly and 41 as young. All patients were treated with platinum-based chemotherapy. Chi 2, log rank, Kaplan-Meier, and Cox model analyses were performed for multiple variables including age, grade of tumor, adequacy of surgery, and dose intensity. The elderly significantly differed from the young in the following analyses: median length of hospitalization, 20 days vs 11 days (P < 0.001); optimum surgery, 79.3% vs 97.5% (P = 0.02); initial chemotherapeutic dose reduction, 15.4% vs 0% (P = 0.02); median survival compared to age, 19.2 months vs 36.7 months (P < 0.03). When survival analysis was performed comparing 17 elderly patients and 40 younger patients who had optimum surgery and optimum initial chemotherapy, the median survival remained essentially unchanged, 22.0 months vs 36.7 months. There were differences in treatment intensity between young and old, however, the indications generally were valid and when analyzed by the Kaplan-Meier and Cox model, these differences became insignificant. It was concluded that when elderly patients can undergo aggressive surgical and chemotherapeutic management, survival remained significantly decreased for aged compared to younger patients. Physician bias was not a major factor accounting for the poorer survival observed in elderly patients. Age was the most significant variable related to survival and could not be accounted for by differences in adequacy of surgery or dose intensity. PMID- 8482567 TI - Platinum chemotherapy during pregnancy for serous cystadenocarcinoma of the ovary. AB - Ovarian carcinoma in pregnancy remains a rare event. Although concern regarding the gestation complicates therapy, platinum drug-based combination chemotherapy is often deemed warranted in such cases. We report the antepartum use of cisplatin, followed by carboplatin, for an ovarian serous cystadenocarcinoma. During this treatment, serial sonographic assessment of fetal morphometric parameters and biophysical profiles with fetal heart rate monitoring were performed to document fetal well being. Platinum-DNA adducts were measured in maternal blood, placenta, fetal amniotic cells, and cord blood. This report represents an attempt to define platinum drug transfer in utero and fetal growth and development during therapy and to document the first use of carboplatin in pregnancy. PMID- 8482568 TI - Interpreting figurative language expressions. AB - Interpretations of figurative language expressions were compared in matched samples of 28 language/learning-disabled (LLD) and 28 academically achieving (non LLD) adolescents. LLD adolescents performed significantly poorer than their non LLD age peers. All but 1 of 12 figurative language expressions contributed to the significant group difference. Stepwise discriminant analysis identified 3 figurative expressions as the best single predictors of an LLD group placement. Qualitative analysis indicated that the LLD group produced predominantly literal error interpretations while the non-LLD controls produced predominantly partial and/or incomplete error interpretations. The results indicate that interpretation and matching of figurative language expressions can assess levels of acquisition of metaphoric ability by adolescents and provide suggestions for intervention. PMID- 8482569 TI - [Psychogenic aspects of functional dysphonia]. AB - In order to estimate the significance of the psychogenic factor in the etiology of functional voice disorders on the basis of relevant psychological dimensions we compared patients with functional dysphonia, aphonia and a normal control group by means of an empirical-psychological test procedure. Psychogenic conditions proved to be a major factor in the etiology of aphonia, whereas such an interrelation turned out only partially in patients with functional dysphonia. The conclusion can be that psychogenic aspects are not necessarily of exceeding importance in the etiology of functional dysphonia. If no differentiation is made between the two kinds of voice disorders an overestimation of psychogenic influence might occur. PMID- 8482570 TI - Normal values and predictive equations for aerodynamic function in British Caucasian subjects. AB - Many useful objective measurements of air volume and flow may be made with a high degree of validity and reliability using present-day respirometers within a speech clinic. We have studied measures of aerodynamic function in 76 British Caucasian subjects and derived reference equations for mean flow rate (MFR), phonation quotient (PQ), vocal velocity index (VVI), phonation time and the phonation volume/vital capacity ratio. Measures from resting breathing patterns have also been investigated. Age was found to be an important determinant in the reference equations. MFR, PQ and VVI were all greater than previously reported. The equations derived in this study should provide a more appropriate assessment of aerodynamic function than the previously reported normal ranges. PMID- 8482571 TI - Evaluation of speech after completed late closure of the hard palate. AB - Speech was analyzed about 1 year postoperatively in 30 patients with cleft lip and palate who were the first ones to undergo late closure of the hard palate in Gothenburg, Sweden. Fourteen had bilateral and 16 had unilateral clefts. Soft palate closure had been performed at the mean age of 8 months, and the hard palate was closed at the mean age of 8 years with a range of 7-11 years. Imitated and spontaneous speech was analyzed at an average of 15 months after palatal repair. Six percent had moderate to severe hypernasal speech and 23% had retraction of dental consonants. No glottal articulation was found. Hoarseness and deviant s articulation were frequent. For 6 of the patients the same speech analysis was also made 1-3 months postoperatively. At this time there was no change in the speech of these 6 children compared with preoperative speech. Thus, the closure of the palate did not improve the speech directly. The improvement of the speech seems to be a gradual process. PMID- 8482572 TI - Speech rehabilitation in dysarthria. AB - Although the usefulness of speech rehabilitation in disorders such as asphasia is now recognized, many clinicians estimate that speech treatments for dysarthrics are of limited value. The conceptual approach to dysarthrias is a physiological approach that emphasizes the component-by-component analysis of the peripheral speech mechanism. The selection and sequencing of treatment procedures follow directly from the physiological nature and severity of involvement in each component. PMID- 8482573 TI - Inflammatory changes as a risk factor in the development of phonoponosis. AB - Inflammatory changes of the upper respiratory airway mucosa are very often observed in phonoponoses. While treating phonoponoses, we frequently find that general practitioners and even otorhinolaryngologists, while paying greatest attention to this component, neglect treatment for voice and phonatory pattern disturbance, and the patients are referred to a phonitrician with delay. The aim of the work is to study the frequency of inflammatory processes of the upper respiratory airways in phonoponoses and an attempt to establish the connection between these changes and the development of phonoponoses. The study involved 358 patients with different types of phonoponoses. Inflammatory changes were found in 84.6% of the cases, which was statistically highly significant. With inflammatory processes on the vocal organs the appearance of phonoponoses is facilitated. In that sense the inflammatory processes are risk factors in the appearance of phonoponoses. PMID- 8482574 TI - Effect of selegiline on speech performance in Parkinson's disease. AB - Comprehensive speech examinations of 10 equally affected subjects with moderate, treated Parkinson's disease were performed before and 4 weeks following initiation of treatment with selegiline (deprenyl), with other drug therapies unchanged. Forty different measures relating to the speech processes of respiration, phonation, resonation, articulation and prosody were examined to measure changes in performance due to selegiline. Significant improvements were noted for 8 of the 40 measures, with these improvements relating to the speech processes of articulation and respiration. The potential interactive effects of comedication are discussed. In addition, previously undescribed comprehensive speech characteristics of moderate Parkinson's disease are presented and discussed. PMID- 8482575 TI - Sequence divergence of B2m alleles of wild Mus musculus and Mus spretus implies positive selection. AB - Mouse beta 2-microglobulin (beta 2m) is polymorphic. Sequences of five allelic wild mouse B2m genes have been determined from the large exons of genomic DNA using the polymerase chain reaction. Relative to the standard B2m(a) allele, the products of four alleles of Mus musculus origin (w2, w3, w4, and w5), differ by only one or two amino acids. w5 has a single nucleotide change, Asp85-->Val, and is identical to the c allele. w3 has two changes, Val(-13)-->Ile and Lys44-->Glu. w2 differs at Arg81-->Thr and w4 at His34-->Gln, and they share the Asp85-->Val change with B2mc and B2mw5. w5 and c cells are lysed by S19.8, a monoclonal antibody specific for beta 2mb (Ala85), in a complement-mediated cytotoxicity assay, whereas w4 cells are not. Thus, distant changes appear to introduce subtle conformational effects on beta 2m structure. Five independent isolates of Mus spretus (w1) differ the most from B2m(a), with 12 amino acid changes and only one silent substitution. Replacements predicted from the nucleotide sequence occur in loops of the molecule facing away from the class I heavy chain and not in regions where beta 2m associates with class I alpha 3 domains. Concordantly, the w1-5 allelic forms of beta 2m associate well with H-2 heavy chains. The many amino acid changes in the spretus sequence and the paucity of silent substitutions suggest that B2m has been subject to positive selection. PMID- 8482576 TI - Characterization of the rhesus macaque (Macaca mulatta) equivalent of HLA-F. AB - Nucleotide sequence analysis of rhesus macaque major histocompatibility complex class I cDNAs allowed the identification of the orthologue of HLA-F, designated Mamu-F. Comparison of Mamu-F with earlier published human and chimpanzee orthologues demonstrated that these sequences share a high degree of similarity, both at the nucleotide and amino acid level, whereas a New World monkey (cotton top tamarin) equivalent is more distantly related. Exon 7, encoding one of the cytoplasmatic domains, is absent for all primate Mhc-F cDNA sequences analyzed so far. In contrast to the human, chimpanzee, and rhesus macaque equivalents, the cotton-top tamarin Saoe-F gene seems to have accumulated far more nonsynonymous than synonymous differences. PMID- 8482577 TI - New beta chain-encoding Mhc class II genes in the carp. PMID- 8482578 TI - The IL-2 receptor beta chain gene (Il-2rb) is closely linked to the Pdgfb locus on mouse chromosome 15. PMID- 8482579 TI - Immunodominance in the T-cell response to multiple non-H-2 histocompatibility antigens. V. Chromosomal mapping of the immunodominant cytotoxic T-cell target-1 (CTT-1). PMID- 8482580 TI - Peptide motifs of HLA-B35 and -B37 molecules. PMID- 8482581 TI - Amino acid sequences of seven V beta, eight V alpha, and thirteen J alpha novel human TCR genes. PMID- 8482582 TI - "You've come a long way, baby". PMID- 8482583 TI - Characterization of a class Ib gene of the rat major histocompatibility complex. AB - The cDNA and a partial genomic sequence of a rat class I major histocompatibility (RT1) gene, 11/3R, is reported here. The sequence contains several unique amino acid residues at certain positions, mutations in exon 7 (which is not expressed), a mutation of the canonical exon 8 stop codon to a sense codon, and includes a long 3' untranslated region (utr). The structure of exon 7 differs from that found in most rat class I genes and resembles exon 7 of most H-2K,D,L,Q genes. Parts of the 3' noncoding region are homologous to the RT1.A-4 and certain H-2 genes. Expression is detectable by northern blot analysis in mitogen-stimulated lymphocytes only, by polymerase chain reaction (PCR) in each tissue tested. After transfection into L cells 11/3R can be shown to be expressible at the cell surface. Probes derived from the 3' noncoding part crosshybridize with a number of restriction fragments which map to the RT1.C region, thus defining a subfamily of RT1.C region genes. Several members of this subfamily are deleted in the lm1 RT1 mutant. The 11/3R gene presents typical features of a class Ib gene. Aspects of evolution and the potential function of the gene are discussed. PMID- 8482585 TI - A genetic analysis of human minor histocompatibility antigens demonstrates Mendelian segregation independent of HLA. AB - An analysis of the genetic traits of human minor histocompatibility (mH) antigens is, unlike with inbred mice, rather complicated. Moreover, the fact that mH antigens are recognized in the context of MHC molecules creates an additional complication for reliable segregation analysis. To gain insight into the mode of inheritance of the mH antigens, we relied upon a series of HLA-A2-restricted cytotoxic T-cell (CTL) clones specific for four mH antigens. To perform segregation analysis independent of HLA-A2, we transfected HLA-A2-negative cells with the HLA-A2 gene: this results in the cell surface expression of the HLA-A2 gene product and, if present, mH antigen recognition. The mode of inheritance of the HLA-A2-restricted mH antigens HA-1, -2, -4, and -5 was analyzed in 25 families whose members either naturally expressed HLA-A2 or were experimentally rendered HLA-A2-positive. Analysis of distribution of the mH antigens in the parent population among the mating types, together with their inheritance patterns in the families, demonstrated that the four mH antigens behaved as Mendelian traits, whereby each can be considered a product of a gene with two alleles, one expressing and one not expressing the detected specificity. We also showed that the loci encoding the HA-1 and HA-2 antigens are not closely linked to HLA (lod scores Z (0 = 0.05) <-4.0). Some indication was obtained that the HA 4- and HA-5-encoding loci may be closely linked to HLA. While we are aware of the limited results of this nonetheless comprehensive study, we feel the similarity in immunogenetic traits between human and mouse mH antigens is at least striking. PMID- 8482584 TI - Polymorphism and phylogeny of dinucleotide repeats in human T-cell receptor Vb6 genes. AB - The Vb6 subfamily is the largest reported subfamily of human T-cell receptor (Tcr) genes, with as many as 14 possible members based on variation in reported DNA sequences. A study of the genomic organization of four distinct Vb6 genes indicated that they contained within their introns the uninterrupted dinucleotide repeat (GT)n, with n > 8. DNA amplification primers and conditions were determined which amplified the intron of these four different Vb6 gene segments. All four Vb6 genes tested showed length polymorphism when examined in a group of unrelated individuals. Careful sizing and DNA sequencing showed that the alleles of each gene differed in size by multiples of two base pairs (bp), due to different repeat numbers of the dinucleotide (GT)n. These four microsatellite polymorphisms had from three to ten alleles, and individual heterozygosities of 26% to 83%. The large number of alleles and the high heterozygosity make these polymerase chain reaction (PCR)-based polymorphisms very attractive genetic markers for segregation studies which postulate the presence of autoimmune susceptibility genes within the Tcrb region. Vb6 hybridization to genomic DNA confirmed the relatively large size of the Vb6 subfamily in several hominoid species. Nucleotide sequencing of an intron of the Vb6 genes from other primates revealed the presence of dinucleotide repeats similar to those found in human Vb6 genes. Thus, the (GT)n microsatellite was not only present in the Vb6 intron before Vb6 gene duplication, but was present before speciation of the hominoids. PMID- 8482586 TI - Increases in polycyclic aromatic hydrocarbon content and mutagenicity in a cutting fluid as a consequence of its use. AB - The aim of this study was to evaluate the relationships between the length of time a cutting fluid was used, its content in polycyclic aromatic hydrocarbons (PAHs) and its mutagenic potential. The PAH concentrations were determined by means of a high-resolution gas chromatograph-mass spectrometer in samples of new cutting fluid and in samples used for 3, 6 and 9 months. The following PAHs were measured: phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene+triphenylene, benzo[e]pyrene, benzo[a]pyrene and perylene. Mutagenicity assays were carried out on the aforementioned samples using the Ames test. Salmonella typhimurium TA98 was used as an indicator to show up mutagens capable of inducing frame-shift genetic changes, and Escherichia coli WP2 uvrA was used as an indicator to detect mutagens capable of inducing base pair genetic changes. The mutagenic tests were carried out with and without microsomal activation, using 1:1, 1:10, 1:20 and 1:50 dilutions of cutting fluid samples. An increase in the concentrations of total PAHs over time was observed in the samples of cutting fluid used for 3, 6 and 9 months. The highest percentage increase in PAH concentrations was observed in the 6-month-old sample (10 times the initial concentration, from 45 to 411.8 micrograms of oil). None of the samples were mutagenic to S. typhimurium without metabolic activation or to E. coli with and without metabolic activation. All samples except for the 1:1 diluted sample showed moderate but significant mutagenic activity in the S. typhimurium test with metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482587 TI - Occupational chronic exposure to organic solvents. XIV. Examinations concerning the evaluation of a limit value for 2-ethoxyethanol and 2-ethoxyethyl acetate and the genotoxic effects of these glycol ethers. AB - Two groups of workers occupationally exposed to glycol ethers in a varnish production plant or the ceramic industry were examined. For 19 persons the external and internal exposure was assessed on the Monday and Tuesday after an exposure-free weekend. In the varnish production area the concentrations of 2 ethoxyethanol (EE), 2-ethoxyethyl acetate (EEAc), and 2-butoxyethanol (BE) in air averaged 2.9, 0.5, and 0.5 ppm, respectively, on the Monday, and 2.1, 0.1, and 0.6 ppm, respectively, on the Tuesday. At the same workplaces the mean urinary 2 ethoxyacetic acid (EAA) and 2-butoxyacetic acid (BAA) concentrations were 53.2 and 0.2 mg/l on Monday preshift and 53.8 and 16.4 mg/l on Tuesday postshift. The results show that glycol ethers are very well absorbed through the skin. Therefore biological monitoring is indispensable. To study the kinetics of the toxic metabolite, 17 persons were examined for their excretion of EAA in urine during an exposure-free weekend. The median values of the calculated half-times were 57.4 and 63.4 h, respectively, which are longer than the values presented in literature until now. According to our calculations the limit value should not exceed 50 mg EAA per liter of urine, which is the current German biological tolerance value (BAT value) for EAA in urine. The maximum concentration value at the workplace (MAK value) for EE and EEAc in air should be revised. Finally, the subjects from the varnish production plant as well as a group of reference persons were studied for cytogenetic effects of glycol ethers (sister chromatid exchange, micronucleus test). Such effects could not be detected. PMID- 8482588 TI - Patterns of electromyographic shoulder muscle fatigue during MTM-paced repetitive arm work with and without pauses. AB - Surface electromyographic recordings from the lateral and the cervical portions of the descending trapezius muscle and from the infraspinatus muscle were assessed for 12 female subjects during performance of a standardized repetitive work simulation task involving 1 h of continuous work and 1 h with introduced pause activities. Discomfort ratings and ratings of perceived exertion were also assessed. Work pace was determined according to MTM-110 (Methods-Time Measurement) as 2466 cycles for both working hours. Muscle fatigue with a decrease in the mean power frequency and an increase in root mean square amplitudes was found both during continuous work and during work with pause activities. The muscle fatigue was less pronounced when pause activities were introduced into the work. Five-minute fatigue patterns were lower during the second hour, indicating adaptation to the work task and work pace. The ratings of perceived exertion and discomfort were similar during work with and without pauses and were higher during the second hour of work. Both work pace and a varied muscle activity pattern are of importance for prevention of muscle fatigue. PMID- 8482589 TI - Determination of urinary alkoxyacetic acids by a rapid and simple method for biological monitoring of workers exposed to glycol ethers and their acetates. AB - In control subjects and workers exposed to glycol ethers and their acetates, we determined the urinary metabolites (three alkoxyacetic acids) by a simple and rapid method. Levels of urinary metabolites were significantly higher in the solvent workers than in the nonexposed subjects. The exposure levels measured by personal monitoring of breathing zone air were far below the threshold limit value. The present results indicate that determination of urinary alkoxyacetic acids by the practical method used here is useful for evaluating excessive exposure to solvents. PMID- 8482590 TI - Salivary cortisol for monitoring circadian rhythm variation in adrenal activity during shiftwork. AB - To examine the validity of salivary cortisol for monitoring circadian rhythm variation in adrenal activity during shiftwork, saliva and blood samples were collected at 4-h intervals in experimental short-term shifts, i.e., day (work 0830-1600 h; sleep 0030-0800 h), evening (work 1630-2400 h; sleep 0430-1200 h), and night (work 0030-0800 h; sleep 1230-2000 h) shifts over 2 days. Cortisol levels, determined by radioimmunoassay, and the circadian profiles of saliva and sera were compared. The salivary cortisol showed relatively low levels, the 2-day mean value being 3.1%-3.3% that of serum total cortisol through all shifts. Significant differences in the serum to saliva cortisol ratios were noted among shifts and subjects. When expressed as a relative percentage of a 2-day mean value, however, salivary cortisol paralleled the modified circadian profiles of serum total cortisol of the evening and night shifts, with no significant time lag and no difference in magnitude. The cosinor analysis supported this finding. Thus, salivary cortisol appears to be an excellent measure for monitoring circadian rhythm variation in adrenal activity in healthy individuals during shiftwork. PMID- 8482591 TI - Blood concentrations of carbon disulphide in dithiocarbamate exposure and in the general population. AB - Blood carbon disulphide (CS2), both free and total, was determined by gas chromatography-mass spectrometry in 112 "normal" subjects and in 20 subjects employed in a dithiocarbamate factory, comprising ten blue-collar workers involved in dithiocarbamate production and ten white-collar office staff. The ten production workers were examined over two workshifts, the first at the beginning of the week (Monday) and the second after an intervening period of at least 1 day. Three blood samples were taken for each shift studied, one prior to starting work, one at the end of the shift and the third 16 h after the end of the shift (on the following morning). The mean CS2 blood levels measured in the 112 normal subjects was 663 ng/l for the free fraction and 3178 ng/l for the total. In 16 blood samples taken from the ten dithiocarbamate factory office workers, the mean free and total CS2 blood levels were 846 and 4140 ng/l, respectively, i.e. not significantly different from those observed in the normal subjects. At the end of the first 8-h shift, the ten dithiocarbamate factory production workers had free and total CS2 values of 1070 and 8471 ng/l, respectively, which were significantly higher than those observed prior to starting work (240 and 4738 ng/l). All the total CS2 levels measured in the shop-floor workers, with the sole exception of the values recorded prior to the start of the Monday shift (4738 ng/l), ranged from 7047 to 8471 ng/l and were significantly higher than those measured in the white-collar staff (4140 ng/l). PMID- 8482592 TI - Hygienic behaviour in chromium plating industries. AB - The impact of hygienic behaviour on the uptake of chromium has been studied in two small chromium plating factories. The correlation between the environmental monitoring measure (Cr-A) and the biological monitoring measure (Cr-U) varied between the two factories. In one factory (I) the correlation between Cr-U and Cr A was 0.68 (P < 0.001), while in the other factory (II) it was negative (r = 0.64, P = 0.03). However, in both populations a significant impact of hygienic behaviour on the variance in Cr-U levels could be detected. In factory I, explained variance could be enhanced to R2 = 0.94 (P < 0.001) when considering expressions of hygienic behaviour. In factory II, a strong relation proved to exist between Cr-U and dermal uptake. For the various questions referring to skin problems and possible dermal uptake, the correlation with Cr-U is up to 0.70 (P = 0.03). When comparing the results for the two factories, it is shown that in addition to individual differences in hygienic behaviour, general hygienic conditions also have an impact on uptake of chromium. In factory II, where many efforts were made to prevent exposure to chromium, Cr-U was significantly lower than in factory I (P < 0.001). PMID- 8482593 TI - Changes in nasal lavage fluid due to formaldehyde inhalation. AB - The aim of the study was to characterize the nature of the formaldehyde-induced nasal response consisting in symptoms of rhinitis and changes in nasal lavage fluid. Eleven healthy subjects and nine patients with specific skin sensitization were provoked in a toxicological chamber with formaldehyde at a dose of 0.5 mg/m3 over 2 h. Nasal lavage was performed prior to and immediately after provocation and 4 and 18 h later. Provocation with formaldehyde caused transient symptoms of rhinitis and prolonged changes in nasal washings. There were increases in the number and proportion of eosinophils and elevated albumin and total protein levels in nasal lavage fluid 4 and 18 h after provocation. No difference in the nasal response to formaldehyde was found between patients with skin sensitization and healthy subjects. These data confirm the irritative effects of formaldehyde and are also suggestive of nonspecific proinflammatory properties when formaldehyde is inhaled at a low (0.5 mg/m3) dose. PMID- 8482594 TI - Respiratory function in greenhouse workers. AB - Respiratory findings were studied in a group of 135 female and 32 male workers employed in greenhouses. In addition 51 women and 30 men were studied as a control group. Exposed women had significantly higher prevalences of chronic cough, dyspnea, chest tightness, and rhinitis (P < 0.01) than the controls. Among the men, only rhinitis was more prevalent in greenhouse workers (P < 0.01) than in controls. Smokers had higher prevalences of all chronic respiratory symptoms than nonsmokers, but the differences were statistically significant only for chronic cough and rhinitis in women and for chronic phlegm in men. There was a high prevalence of acute symptoms during work. A large number of greenhouse workers complained of skin reactions to plants and pesticides (women: 37.8%; men: 34.4%). Workers had significantly lower mean ventilatory capacity measurements (except in the case of forced vital capacity) when compared to standard predicted values. Smokers and nonsmokers had similar values of lung function expressed as percentages of the predicted values. Greenhouse workers exposed for more than 10 years had a significantly lower FEF25, measured as a percentage of the predicted value, than workers exposed for less than 10 years. Our data indicate that occupational exposure to greenhouses may be associated with the development of acute and chronic respiratory symptoms and impairment of ventilatory capacity. PMID- 8482595 TI - Study of the neurobehavioural toxicity of styrene at low levels of exposure. AB - Thirty workers in a dockyard exposed to concentrations of styrene lower than the TLV-TWA of 50 ppm and 30 control workers not subject to exposure but employed by the same company were subjected to three psychometric tests on one Monday morning and evening. The results were usually better in the evening than in the morning in both groups, which proves the lack of acute intoxication at the end of the day at this level of exposure. On the other hand, all of the tests conducted on the exposed subjects are significantly less good than those on the controls. The results suggest the existence of minor but significant organic mental disorders in the subjects exposed to a mean dose of 30 ppm in this study. These results are inconsistent with those of several recent studies. The advisability of lowering the TLV of 50 ppm in discussed. PMID- 8482596 TI - Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene. AB - The correlation between exposure to three xylene isomers and resulting urinary excretion of corresponding methylhippuric acid (MHA) isomers was studied among 175 Chinese workers of both sexes who had been predominantly exposed to xylenes (exposure to xylenes accounting for 70% or more of the total exposure on a ppm basis). Nonexposed controls (281 men and women) were also studied to define the background level of MHAs in urine. The solvent exposure of xylene-exposed workers during their workshift was monitored by diffusive sampling of breathing zone air, and MHAs in shift-end urine were determined by high-performance liquid chromatography. Regression analysis showed that the concentration of each MHA isomer correlated significantly with the time-weighted average intensity of exposure to the corresponding xylene isomer, and therefore the correlation between the sum of three xylene isomers in air and that of three MHA isomers in urine was also significant; the slope of the regression line was essentially the same among the three isomers. The calculated regression line suggested that the urinary MHA level after hypothetical exposure to xylenes at 100 ppm will be somewhat less than the proposed biological exposure index and biological tolerance value. Two social habits of smoking and drinking in combination suppressed the conversion of xylenes to MHAs in male workers. PMID- 8482597 TI - [The role of cytokines for the pathogenesis of psoriasis]. AB - Psoriasis is an inflammatory skin disorder characterized by marked hyperproliferation of keratinocytes in association with vascular expansion, fibroblast activation, leucocyte infiltration, and alterations of eicosanoid metabolism and of cytokine production. However, it is unclear at present whether these changes are the cause or the effect of the significantly increased keratinocyte turnover. More than one mechanism is involved in triggering active psoriasis; genetic predisposition and environmental factors affecting the immune system have a particularly important role. Most of the therapeutic regimens used for the treatment of psoriasis are immunosuppressive. Therefore, it is tempting to speculate that a specific defect of the immune system is the major pathogenic principle in psoriasis. There are several lines of evidence suggesting that changes in cytokine production by keratinocytes and immunocompetent cells in the skin of the patients, particularly of interleukin-6 and TGF alpha, may play an important part in propagation of the inflammatory response in psoriasis. Further studies are required to find how far local T-cell activation is involved as a basic mechanism of initiation and maintenance of the psoriatic inflammatory response. Accordingly, parameters such as the evaluation of cytokine production in vitro and in vivo and the measurement of cellular activation products may be useful in the diagnosis and monitoring of psoriasis. PMID- 8482598 TI - [Treatment of vitiligo with phenylalanine and UV-A]. AB - Seven patients with generalized vitiligo were treated with 100 mg/kg body weight phenylalanine in combination with UV-A. A 20% repigmentation of the vitiligenous area was achieved in only one patient. Three patients each showed either a sparse follicular repigmentation or no effect at all. Because of the disappointing therapeutic results and possible side effects, we cannot recommend a therapy with phenylalanine and UV-A for vitiligo. PMID- 8482599 TI - [Prognosis and success of inpatient psychotherapeutic dermatologic treatment of neurodermatitis patients]. AB - A large group of patients with atopic dermatitis underwent a combination of psychotherapy dermatological treatment, and 40 were selected for evaluation. Most of them had benefited from the cure, particularly those who themselves felt they were emotionally disturbed, those who were well educated and those with functional complaints. PMID- 8482600 TI - [Polymorphous light dermatosis. Clinical data and test results]. AB - In a retrospective study, the clinical data of 424 patients, 340 (= 80.2%) female and 84 (= 19.8%) male, with polymorphous light eruption (PLE) were evaluated; 89.1% of the patients had skin type II or III (according to Fitzpatrick). 368 Photoprovocation testing was performed on 332 of these cases. The duration of PLE was (mean +/- SD) 7 +/- 6.9 years, and the age at onset of the disease was 28 +/- 14 years. In 40.1% of the patients PLE developed without seasonal accentuation. Predilection sites for skin lesions were the extensor aspects of the upper arm or forearm (69.0%/66.7%) and the chest (59.5%); the face and the back of the hand were less frequently (41.0%/40.8%) affected. In most cases (53.6%/18.3%), the skin lesions were papular or erythemato-urticarial in type. The minimal erythema dose for UV-B was found to be normal in all 311 cases in which it was assessed. Photoprovocation testing yielded skin lesions of PLE in 38.4% of the female, and in 58.5% of the male patients. The frequency of positive reactions to photoprovocation testing was directly related to the duration of the disease, the persistence of naturally occurring lesions, and the time interval from accidental exposure to the development of lesions. PMID- 8482601 TI - [The pustular bacterid (Andrews). Are there clinical criteria for differentiating from psoriasis pustulosa palmaris et plantaris?]. AB - A case report on the rare entity of "true" Andrews bacterid and a review of the literature are used to illustrate clinical and morphological criteria that allow discrimination between Andrews bacterid and psoriasis pustulosa palmaris et plantaris. The patient noted the eruption of sterile pustules on palms and soles for the first time in his life at the age of 73 during an attack of acute tonsillitis. He had no history of psoriasis and it was also unknown in the family history. In contrast to psoriasis pustulosa palmaris et plantaris, Andrews bacterid becomes manifest as isolated pustules with an erythematous rim, which do not destroy the ridged skin. On the rest of the integument disseminated pustules are seen but no psoriatic stigmata. Thus, apart from the criterion of coincidence with an infection and the short course, we can also differentiate between Andrews bacterid and psoriasis pustulosa palmaris et plantaris on the basis of clinical criteria. PMID- 8482602 TI - [Therapeutic problem. Angiolymphoid hyperplasia with eosinophilia]. AB - A 35-year-old female patient suffered from angiolymphoid hyperplasia with eosinophilia for 9 years, with multiple, exophytic tumours on her left pinna and the surrounding skin. Systemic treatment with gamma interferon and glucocorticoids, intralesional injections of glucocorticoids and argon laser therapy had no effect. After the tumours had been pared away by electrocautery the patient was free of symptoms for 1 year and then developed a small local recurrence. Recurrences are common in angiolymphoid hyperplasia with eosinophilia. Malignant transformation has not been observed. We therefore regard non-radical surgery as the therapy of choice. PMID- 8482603 TI - [Sweet syndrome. Acute neutrophilic dermatosis in multiple myeloma]. AB - A 64-year-old woman complained of reddish plaques that had suddenly appeared on her upper arms and trunk. Histological investigation revealed perivascular distribution of a neutrophilic infiltrate in the upper and mid-dermis; direct immunofluorescence showed deposits of C3 and fibrin in and around the vessels. Laboratory values in the blood, X-ray of the head and fine-needle biopsy of the hip showed the typical pattern of multiple myeloma. After chemotherapy the dermatological lesions improved rapidly, and the plasmocytoma reached remission stage. The diagnosis of Sweet's syndrome was established on the basis of the clinical and histological changes and the improvement observed after steroid therapy. The coincidence with plasmocytoma confirms the interpretation of Sweet disease as a paraneoplastic syndrome. PMID- 8482604 TI - [Extensive metastatic Kaposi sarcoma in chronic immune suppressed bronchial asthma]. AB - In a severely ill 64-year-old man with multilocular Kaposi sarcoma HIV infection was excluded. The decisive factor in the pathogenesis, was long-term immunosuppression with systemic corticosteroids for bronchial asthma. The patient died from cardiorespiratory insufficiency in the course of tumour progression. Autopsy revealed a vast visceral manifestation of Kaposi sarcoma. PMID- 8482605 TI - [Pityriasis-lichenoides-et-varioliformis-acuta-like drug exanthema caused by astemizole]. AB - We report on a 40-year-old male patient who developed an unusual generalized drug eruption taking the form of a histologically confirmed pityriasis lichenoides et varioliformis acuta (PLEVA) after oral intake of the H1-antagonist astemizole. On two occasions, independently repeated medication with astemizole exacerbated the typical rash again. Oral exposure and the specific lymphocyte transformation test confirmed the suspected causal connection between astemizole and PLEVA. PMID- 8482606 TI - [Cerebriform intradermal nevus]. AB - A case is reported of an extended cerebriform intradermal naevus of the scalp. Additional skin findings were generalized small intradermal and compound-type naevi. There were no neurological or other internal anomalies. PMID- 8482607 TI - [Symmetrical cyanosis circumscripta e lipomate]. AB - We report the case of a 78-year-old woman with a symmetrical type of cyanosis circumscripta e lipomate above both knees. Clinical symptoms, pathogenesis and possible treatments are presented. PMID- 8482608 TI - [Osteoma cutis. Multiple miliary osteoma of the face]. AB - Primary and secondary forms of ossification can be distinguished on the basis of the skin, with osteoma cutis occurring in primary forms. Three entities can be differentiated: solitary and generalized osteoma cutis and multiple miliary osteoma of the face. Clinically, multiple papules 2-3 mm in diameter are present, which histologically consist of bony trabeculae enclosing mature fat cells and, occasionally, marrow cells. We describe the clinical, radiological and histological features of a case of multiple miliary osteoma of the face in an otherwise healthy 55-year-old woman. PMID- 8482609 TI - [Is the argon laser contraindicated in the summer?]. PMID- 8482610 TI - [Long-term effect of psoralens?]. PMID- 8482611 TI - [Perforating cutaneous amyloidosis. Comment on the contribution by M. Bacharach Buhles, U. Schultz-Ehrenburg and P. Altmeyer]. PMID- 8482612 TI - [Ross syndrome. Comment on the contribution by P. Itin, P. Hirsbrunner, T. Rufli, P. Fuhr and A. Hagmann]. PMID- 8482613 TI - [Congress of the "Epidemiology, Biostatistics and Informatics" Professional Association of the German Dermatologic Society and the Society of Medical Informatics, Medical Biometry and Epidemiology, Zurich 22-23 May 1992]. PMID- 8482614 TI - [The Berlin Pathogenic Neisseriae Conference]. PMID- 8482615 TI - [Antimycotic drugs. Part II]. PMID- 8482616 TI - Therapeutic effect of infused Fluosol-DA/carbogen with ephedrine, flunarizine, or nitroprusside. AB - The perfluorochemical emulsion Fluosol-DA plus carbogen breathing has been shown to increase the effectiveness of radiation therapy in preclinical solid tumors when the emulsion was administered by i.v. bolus injection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. PURPOSE: We hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly. METHODS AND MATERIALS: In the present study, the alpha/beta agonist ephedrine, the Ca2+ channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested. RESULTS: Ephedrine administration resulted in a decrease in the radiation plus Fluosol-DA +/- carbogen antitumor effects in both the Lewis lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine administration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both tumor systems. Even with flunarizine administration Fluosol-DA delivered slowly was less effective than when the emulsion was given rapidly. Flunarizine with Fluosol-DA infused i.v. over 30 min followed by carbogen breathing prior to and during radiation therapy resulted in a 1.7-1.6-fold increase in response compared with 2.4-2.2-fold with Fluosol-DA administered by injection i.v. and carbogen breathing prior to and during radiation therapy using growth delay of the Lewis lung carcinoma. The effects of nitroprusside were complex. This drug had considerably more effect at 10 Gy than at higher radiation doses. CONCLUSION: These studies suggest that Fluosol-DA given by i.v. injection may increase tumor perfusion and that a drug like flunarizine may be beneficial if the Fluosol-DA is administered slowly followed by carbogen breathing and radiation therapy. PMID- 8482617 TI - Deep regional hyperthermia: comparison between the annular phased array and the sigma-60 applicator in the same patients. AB - PURPOSE: Several institutions have accumulated clinical experience with the annular array as well as with the Sigma applicator. There exist only limited data in comparison of both heating devices possibly favoring the annular array over the Sigma applicator with regard to tumor temperatures and acute toxicity. The objective of this study was to record temperature distributions at identical sites in tumor and normal tissue in the same patients treated with each device. METHODS AND MATERIALS: Eighteen patients with advanced pelvic tumors were treated on successive occasions with regional hyperthermia using the annular phased array applicator usually driven at 60-80 MHz or the Sigma applicator usually driven at 70-90 MHz. In all patients detailed thermal mapping and temperature analysis for tumor and normal tissues could be performed. RESULTS: Regardless the device used the acute toxicity was treatment limiting in nearly 50% of the treatments. Systemic stress was treatment limiting in 30% of the treatments with both devices although systemic parameters (core temperature, heart rate, changes in blood pressure) were higher with the annular array. The overall mean minimum, average and maximum tumor temperature observed were 39.5 +/- 1.0 degrees C, 40.9 +/- 1.4 degrees C, 42.7 +/- 2.3 degrees C for the annular array and 39.3 +/- 0.9 degrees C, 40.9 +/- 1.4 degrees C, and 42.5 +/- 1.7 degrees C for the Sigma applicator. The time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of all measured sites were 41.7 +/- 2.1 degrees C, 40.8 +/- 1.4 degrees C, 39.9 +/- 1.2 degrees C for the annular array and 41.7 +/- 1.4 degrees C, 41.0 +/- 1.3 degrees C, and 40.1 +/- 1.0 degrees C, for the S-60. The difference was not statistically significant. With regard to normal tissue temperatures a trend to higher maximum temperatures in the deep muscle and fat tissue was evident for the Sigma applicator. The overall minimum and average normal tissue temperatures in the deep muscle and fat tissue and the rectum and the time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of the measured sites differ not statistically significant. CONCLUSION: These results indicate that there continue to be unresolved limitations in achieving temperature elevation in deep seated tumors of the pelvis with radiative coherent EM wave techniques using amplitude and phase steering capabilities without any special optimization procedure. PMID- 8482618 TI - Anaplastic carcinoma of the thyroid gland treated by radiation therapy. AB - PURPOSE: A retrospective review was performed to investigate the potential role of external beam radiation therapy with or without chemotherapy in anaplastic carcinoma of the thyroid. METHODS AND MATERIALS: Fifty-one patients with a histologically or cytologically proven anaplastic thyroid carcinoma, treated by external beam radiation therapy between January 1970 and December 1986 in the Dr. Daniel den Hoed Cancer Center are the subject of this report. The overall survival, local control rate and pattern of metastasis were analyzed. RESULTS: It was found that the impact of lung metastases and local relapse on survival was appreciable. Patients with metastases but locally free of tumor achieved a median survival of 7.5 months. In patients with local regional residual disease after therapy, an actuarial risk of death of 100% at 8 months and a median survival of 1.6 months was observed. For patients without disease at the end of radiation therapy, an actuarial median survival of 8 months was observed. CONCLUSION: This retrospective analysis supports the data from the literature that local control is indispensable for achieving a higher short-term survival rate, whereas even with local regional control patients might still die soon after the completion of their treatment because of distant metastases, predominantly in the lungs. A potentially new way of treatment, that is the combination of low dose Adriamycin with hyperfractionated external beam radiation therapy to the primary tumor and prophylactic irradiation to the lung, in order to obtain higher locoregional control and diminishing of distant metastases is briefly discussed. PMID- 8482619 TI - A prospective trial of accelerated radiotherapy in the postoperative treatment of high-risk squamous cell carcinoma of the head and neck. AB - PURPOSE: To evaluate the feasibility and toxicity of accelerated fractionation in the postoperative setting in high risk squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Thirty-two patients with high risk pathologic features (e.g., extracapsular extension, positive margins, > or = 4 nodes positive, perineural invasion) were enrolled in an accelerated fractionation schedule, using a modification of the M.D. Anderson concomitant boost technique delivering 63 Gy in 5.3 weeks at 1.8 Gy per fraction. RESULTS: Thirty patients (94%) completed treatment per protocol. Confluent mucositis was seen in 22 (69%) and five patients (22%) required 2 to 4 months for complete healing. Only five patients (16%) lost more than 10% of body weight. At a median follow-up of 32 months (range 22-42 months), the crude infield failure rate is 8/32 (25%). Infield recurrence was significantly associated with the interval from surgery to commencement of radiotherapy; 0/10 (0%) patients beginning radiotherapy within 4 weeks of surgery had infield failures compared to 8/22 (36%) for patients beginning radiotherapy more than 4 weeks after surgery (p = 0.035). CONCLUSION: While acute side effects appear to be increased compared to conventional radiotherapy, we conclude that postoperative accelerated radiotherapy is feasible and has acceptable toxicity in this population. These results support the concept of rapid tumor repopulation after resection. A randomized multi-institutional trial is currently underway to compare conventional and accelerated fractionation in the postoperative setting. PMID- 8482620 TI - Malignant spinal cord compression: a prospective evaluation. AB - PURPOSE: To determine the influence of treatment on ambulancy, pain control and functional outcome of patients with Malignant Spinal Cord Compression. METHODS AND MATERIALS: One hundred and thirty-seven patients with Malignant Spinal Cord Compression presenting or referred to the Department of Radiation Oncology, Westmead Hospital between August 1, 1989 and August 1, 1990 were studied prospectively. Patients were treated with palliative radiation therapy alone, surgery followed by radiotherapy or surgery alone. Two patients were not treated. Post-treatment outcome was assessed in terms of ambulatory status, improvement in pain and functional independence using the Functional Independence Measure. RESULTS: Thirteen of 16 patients (81%) who were ambulant pre-treatment remained ambulant after treatment. Two of 16 patients (16.5%) who were non-ambulant pre treatment became ambulant following treatment. Pain improved following treatment in 22 of 30 patients (73%). This benefit was seen equally for ambulant and non ambulant patients. A high level of functional independence was maintained in patients who remained ambulant. CONCLUSION: We conclude that prompt treatment of patients with Malignant Spinal Cord Compression while still able to walk is effective in maintaining ambulancy and functional independence, and that treatment improves pain in most patients. PMID- 8482621 TI - 3-dimensional optimization of multiple arcs for stereotactic radiosurgery. AB - PURPOSE: During linear accelerator-based radiosurgery, the physicians and physicists need to determine which combination of treatment arcs are "best" with regard to target coverage and incidental dose to adjacent structures. This is a complex problem, especially when targets are geometrically close to critical structures. The purpose of this article is to present a method to mathematically determine a set of arcs to produce desired target and normal structure dose distributions in linear accelerator radiosurgery. METHODS AND MATERIALS: Nonlinear least squares regression was used to determine the table angles and gantry angle arc ranges and their associated beam weights appropriate to linear accelerator radiosurgery. RESULTS: Three cases are presented: (a) critical structure close to target volume; (b) target volume too large for the largest collimator to cover the volume with one isocenter and a standard plan; (c) target volume located within one critical structure and close to another critical structure. The optimized treatment plans are all shown to be superior to a defined standard plan. CONCLUSION: The method successfully enables one to determine nonstandard arcs which achieve the desired results. In particular, the method enables one to find clinical treatment solutions, even when the desired results cannot be a priori defined. PMID- 8482622 TI - The investigation and rectification of field placement errors in the delivery of complex head and neck fields. AB - PURPOSE: To evaluate a novel technique for resolving field placement errors into their components and to quantify the improvement in accuracy potentially achievable by translation and rotation of the radiation beam. METHODS AND MATERIALS: One hundred and eighty-five films (both simulator and portal) from seventeen patients receiving radiotherapy to the head and neck region were analyzed in pairs. The computer based comparisons of complex fields with curved edges employed the intersections of perpendiculars from two reference points with the field periphery to define field match points. Field placement errors were resolved into those due to patient motion within the immobilization shell and those due to incorrect beam position, orientation, or shape. RESULTS: The median and the 95 percentile of the distribution of differences between prescribed (simulator) fields and treated (portal) fields referenced to the patients anatomy were 4.4 mm and 8.9 mm, respectively. The analysis suggests that with appropriate translation and rotation of the beam with respect to the immobilization shell these figures could be reduced to 3.1 mm and 8.2 mm, respectively, confirming the large contribution of patient motion within the shell to field placement accuracy. Comparisons between treated fields indicated smaller variability during treatment than between simulation and treatment. CONCLUSION: The perpendicular intersection method described here was found appropriate for the identification of field match points. The distributions of field placement errors were similar to those in a published study of straight edged fields. Translation and rotation of the applied field with respect to the immobilization shell would generally result in only a small improvement in field placement accuracy. PMID- 8482623 TI - A CT-based evaluation method for permanent implants: application to prostate. AB - A computerized tomography-based 3-dimensional evaluation scheme, using semi automatic seed localization from transverse computerized tomography-images, has been developed for permanent implants. The treatment isodose contour is generated at each scan plane and overlaid on the corresponding target contour for coverage visualization. Volume and surface dose histograms are generated for the target and neighboring normal structures. Dose inhomogeneity within the target is also estimated from the full-width at half maximum of the differential volume dose histogram. The matched peripheral dose is calculated from the ellipsoidal volume approximation for the target. The present evaluation method has been applied here to 10 actual permanent I-125 prostatic implantations. Coverages by 150 Gy and 100 Gy levels are found to range from 78-96% and 91-99% of the target volume, respectively. The average matched peripheral dose is found to be about two times the average peripheral dose (the dose encompassing 99% target) and about three times the average minimum peripheral dose (the dose encompassing 100% target). The dose inhomogeneities within the target volume, in these 10 cases, range from 220-420 Gy. PMID- 8482624 TI - Dose, volume, and tumor-control predictions in radiotherapy. AB - PURPOSE: Tumor volume has a profound influence on the dose required to control a given type of tumor. The most obvious explanation for this is related to the larger number of stem cells which must be sterilized, leading to a more stringent requirement on cell survival. There are, however, other mechanisms by which volume may influence tumor control, such as clonogenic fraction, oxygenation or inter-cellular communication. We investigate the question of whether the effect of volume on tumor control is, in general, predictable on the basis solely of the differing number of stem cells. METHODS AND MATERIALS: We investigate whether the effect of volume on tumor control in four sites can be predicted, using the linear-quadratic formalism, based on the assumption that the number of cells that must be sterilized is directly proportional to the tumor volume. We require that the biological parameters in the model should have plausible values. RESULTS: We find that the results of four clinical data sets, exhibiting a wide range of doses, volumes, and tumor control rates, are consistent with the hypothesis that the number of potential stem cells which must be sterilized is proportional to the tumor volume. CONCLUSIONS: If these considerations are correct, the potential exists that realistic radiobiologically-based dose corrections for tumor size could be routinely made. This applies both to an entire treatment, and also between fractions, as the tumor shrinks. Such an approach may contribute towards optimized radiotherapy. PMID- 8482625 TI - Postoperative irradiation in head and neck cancer. PMID- 8482626 TI - Sequencing adjuvant chemotherapy and radiotherapy in breast cancer patients. PMID- 8482627 TI - Inverted papilloma of the nasal cavity or paranasal sinuses: a malignant benign tumor. PMID- 8482628 TI - Effect of delay in radiation in the combined modality treatment of breast cancer. AB - PURPOSE: To study how the timing of radiation influences local control, overall survival, and disease-free survival in patients being treated with chemotherapy and radiation for a local-regional carcinoma of the breast. METHODS AND MATERIALS: Over a ten year period, 105 patients received chemotherapy and radiation treatments for a local-regional breast cancer. The population was divided into two groups based on the timing of their radiation treatments. Forty eight patients began their radiation within 6 months of their diagnosis (early radiation group). Fifty-seven patients had a delay in their radiation for 6 or greater months in order to first maximize chemotherapy treatments (delayed radiation group). There were no significant differences between the two groups with respect to nodal status, stage of the primary, estrogen receptor status, patient age, or type of surgery performed. The only prognostic parameter that was imbalanced was that of a greater percentage of patients with close or positive margins in the early radiation group compared to the delayed radiation group (69% versus 38%, p < 0.02). RESULTS: Comparisons of local control, overall survival, and disease-free survival between the early radiation patients and delayed radiation patients all favored the early radiation group. Respective 8-year actuarial rates were: local control--98% vs. 76%, p = 0.004; overall survival- 80% vs. 52%, p = 0.016; disease-free survival--71% vs. 48%, p = 0.008. The differences continued to be significant in a multivariate Cox regression model comparison: p = 0.011, p = 0.050, p = 0.009. There was only one death from intercurrent disease, so that overall survival approximated cause-specific survival to an accurate degree. CONCLUSIONS: In patients requiring chemotherapy and radiation treatments for a local-regional breast cancer, a delay in the initiation of radiation for a period of 6 months or greater from diagnosis resulted in a higher local failure rate. Furthermore, this higher local failure rate was associated with an increased rate of distant metastases and a decreased overall survival rate. PMID- 8482629 TI - Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. AB - PURPOSE: This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors. METHODS AND MATERIALS: Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving > 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk. RESULTS: The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of < or = 54 Gy had a significantly higher primary failure rate than those receiving > or = 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at > or = 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, > or = 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status > or = 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received > or = 63 Gy. CONCLUSION: With daily fractions of 1.7 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio. PMID- 8482630 TI - Brachytherapy for stage I & II oral tongue cancer: an analysis of past cases focusing on control and complications. AB - An analysis of the therapy used for 370 tongue cancer patients has been made, said patients having been treated by interstitial irradiation alone or by combined external irradiation and brachytherapy (Stage I:90 cases, IIa: 196 cases; and IIb: 84 cases). The neck was followed by close follow-up (304 cases), treated by elective neck irradiation (56 cases), or underwent operation at the time of local recurrence (10 cases). The results have shown that the 5-year survivals for Stages I, IIa, and IIb were 84%, 78%, and 72%, respectively. further, the 5-year primary control was 85% for tumors of the superficial type, 79% for tumors of the exophytic type, and 45% for tumors of the infiltrative type (p < 0.004). In non-electively irradiated patients, a neck metastasis occurred in 31% in Stage I, 41% in Stage IIa, and 51% in Stage IIb. Finally, 110 patients incurred radiation-induced complications (110/291 = 38%) and 11 patients (11/291 = 4%) required a surgical procedure. Brachytherapy for tongue cancer achieved results that are comparable with surgery. The analysis also revealed that the introduction of computer dosimetry and the use of a spacer (a dental guard) in brachytherapy have achieved superior results in the management of a tongue cancer. PMID- 8482631 TI - Radiotherapy is successful treatment for orbital lymphoma. AB - PURPOSE: To describe the clinical presentation, treatment technique, outcome and complications in a large single institutional experience using radiotherapy for treatment of orbital lymphoma. METHODS AND MATERIALS: Twenty-five patients with lymphoma of the orbit or ocular adnexa were treated with radiotherapy at Stanford University Medical Center during the fourteen year period, 1977-1991. Patients were staged using the Ann Arbor criteria with chest x-ray, computerized tomography of abdomen and orbits, lymphangiogram, and bone marrow biopsy. Patients with disease localized to the orbits as well as those with disseminated disease and symptomatic orbital lesions were treated. Thirty-one involved eyes were treated. Mean radiotherapy dose was 35.3 Gy, with a range of 28 Gy to 40.2 Gy. Lens protection was used in all cases. Two patients with diffuse large cell lymphoma also received chemotherapy as part of their initial treatment. Follow-up ranged from 10 months to 13 years, with a mean follow-up time of 4 years. RESULTS: Twenty patients had disease confined to one or both orbits (Stage I). One patient had a monoclonal atypical infiltrate, while the remainder had a histologic diagnosis of malignant lymphoma: diffuse small lymphocytic, 13; follicular mixed, 3; diffuse small cleaved, 3; diffuse large cell, 2; follicular small cleaved, 1; follicular and diffuse small cleaved, 1; undifferentiated, 1. Two local relapses occurred; the actuarial 5-year freedom from local relapse is 89%. Actuarial 5-year freedom from distant relapse, freedom from any relapse and overall survival are 77%, 70%, and 93%, respectively. Acute complications of treatment were mild. Late complications included transient cystoid macular edema (one patient), asymptomatic subcapsular and medial sector cataract formation (two patients), retinopathy (two patients), mild eyelid retraction (one patient), and dry eye with secondary conjunctivitis (one patient). CONCLUSION: Carefully planned radiotherapy with lens shielding is an effective and safe treatment in the management of orbital lymphoma. We recommend megavoltage radiation doses of 30-35 Gy in 180-200 cGy fractions for low grade lesions, and 36-40 Gy for intermediate and high grade lesions. PMID- 8482632 TI - Management of inverted papilloma of the nasal cavity and paranasal sinuses: importance of radiation therapy. AB - PURPOSE: Locally advanced inverted papilloma and inverted papilloma associated with squamous cell carcinoma are at high risk of local failure due to limitations of surgical resection resulting in repeat surgical procedures. The role of adjuvant radiation therapy is poorly defined. This study reviews a single institution experience of radiation therapy in the management of this disease. METHODS AND MATERIAL: Between 1977 and 1990 25 patients were treated at the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary with radiation therapy for inverted papilloma (seven patients) and inverted papilloma associated with squamous cell carcinoma (18 patients) of the nasal cavity and paranasal sinuses. All patients presented with locally advanced invasive tumors; 5 of 7 with inverted papilloma had previous resections and 4 of 18 with associated squamous cell carcinoma had history of prior surgical excisions of inverted papilloma only (three patients) or inverted papilloma with squamous cell carcinoma in situ (one patient). Sixteen patients underwent radiation treatment following gross total resection, eight patients after subtotal tumor resection and one patient was inoperable by local invasion and received radiation therapy alone. RESULTS: Local control was achieved in 6 of 7 patients with inverted papilloma only and one patient required additional resection for persistent disease. Of 18 patients with associated squamous cell carcinoma, 17 were locally controlled after radiation therapy and one had persistent tumor. One patient failed locally 3 years after treatment. With a mean observation time of 4.8 years (range: 0.5-12.9 years) all seven (100%) patients with inverted papilloma only and 15 of 18 (83%) patients with associated invasive carcinoma are alive and without evidence of disease. Three patients with inverted papilloma associated with squamous cell carcinoma died, two patients as a result of their disease (one patient with persistent disease, one patient after local failure) and one patient of intercurrent disease. No failure in either regional lymph nodes or at distant sites was recorded. In the majority of cases radiation therapy was well tolerated. CONCLUSIONS: Combined radiation therapy and surgery can offer excellent long-term control and should be considered in patients with history of recurrent disease, in the presence of suspected residual disease, after incomplete resection or for unresectable lesions. Patients with associated squamous cell carcinoma have a more aggressive course, however radiation therapy still has the prospect of permanent disease-free survival in patients who achieve local control. PMID- 8482633 TI - Radiotherapy alone for squamous cell carcinoma of the nasal vestibule: management of the primary site and regional lymphatics. AB - PURPOSE: To examine patterns of failures and complications in invasive squamous cell carcinoma of the nasal vestibule treated with radiotherapy alone. METHODS AND MATERIALS: Thirty-nine patients are reported with two-year minimum follow-up. Twenty-nine patients had tumors that were previously untreated; 10 were recurrent after prior surgical resection. Twelve patients received external beam alone, 18 had external beam followed by a radium implant, and nine had radium implant alone. RESULTS: Local control in patients eligible for analysis was as follows: T1, 11 of 13; T2, 6 of 6; and T4, 12 of 17 (1988 AJCC skin cancer staging classification). Previously untreated tumors and tumors recurrent after surgical excision alone had similar local control, stage for stage. Among T4 tumors, local control with radiotherapy was achieved in 11 of 13 lesions measuring < 4 cm in diameter versus 1 of 4 of those measuring > or = 4 cm. Of 37 patients with clinically negative regional nodes at presentation, 32 were managed with observation alone; of those eligible for 1-year minimum follow-up, 4 (15%) of 27 developed disease in the regional lymphatics. All regional node failures have been salvaged. In general, cosmesis was very good and complications were minimal. CONCLUSION: Radiotherapy in this series proved to be an effective and cosmetically favorable alternative to surgery for nasal vestibule carcinoma. Elective treatment of the regional lymphatics is not warranted in early stage, previously untreated patients, but should be considered for selected advanced and recurrent lesions. PMID- 8482634 TI - Alterations in growth phenotype and radiosensitivity after fractionated irradiation of breast carcinoma cells from a single patient. AB - PURPOSE: To investigate growth regulation and radiosensitivity in surviving clonogens after fractionated irradiation. METHODS AND MATERIALS: Four breast carcinoma cell lines isolated from the primary tumor (21NT, 21PT) and metastases (21MT-1, 21MT-2) of a single patient were exposed to cumulative radiation doses of 30 Gy yielding cell lines designated-IR with respect to their parent. The irradiated lines were then compared to their parent for serum-and growth factor requirements under defined media conditions, ability to proliferate in soft agar, concentration of TGF-alpha in conditioned medium, and radiosensitivity. RESULTS: The irradiated lines showed no change in proliferative doubling times under serum and growth factor-supplemented media conditions. A single line, 21MT-1-IR, acquired a limited ability to proliferate in serum-and growth factor-deplete medium with a day 2-4 doubling time of 44.5 hr. Three lines, 21MT-1-IR, 21MT-2 IR, and 21NT-IR, formed colonies in soft agar in contrast to none of the unirradiated parent lines. There were significant 6-8 fold increases in conditioned media TGF-alpha concentrations for 21MT-2-IR and 21NT-IR cells. The 21MT-1-IR and 21NT-IR cells were significantly less radiosensitive than their respective parent lines. This decrease in radiosensitivity appeared to be at least partially mediated by a released factor as the radiosensitivity of 21MT-1 cells was significantly decreased by pre-incubation with conditioned medium from 21MT-1-IR cells. CONCLUSION: Radiation-induced changes in growth phenotype vary with respect to clonal origin of the cell line and may influence the radiosensitivity of surviving clonogens after fractionated treatment. PMID- 8482635 TI - Effect of conjoint administration of tamoxifen and high-dose radiation on the development of mammary carcinoma. AB - PURPOSE: Tamoxifen is currently advocated for post-menopausal breast cancer patients receiving definitive irradiation after limited surgery. The purpose of this study was to assess in an experimental model for breast cancer whether the efficacy of irradiation is altered by conjoint administration of tamoxifen. To this end, rats with small tumors induced by 1-methyl-1-nitrosourea (MNU) were treated with tamoxifen, radiation, or a combination of the two modalities. METHODS AND MATERIALS: Female Sprague Dawley rats were injected i.p. with 50 mg MNU/kg body weight at 50 days of age. At 64 days post carcinogen, the majority of the rats had at least one palpable mammary tumor. At that time radiation with or without tamoxifen treatment was initiated and given 5 days per week for 5 weeks. Radiation dose was 4500 cGy delivered as 25, 180 cGy fractions. Tamoxifen, 500 mg/kg body weight, was administered subcutaneously each day during the irradiation interval. The study was terminated 28 weeks after carcinogen treatment. RESULTS: High dose radiation alone induced a reduction in the size of existing tumors, but resulted in a significant increase in the number of tumors that were detected. Treatment with tamoxifen alone also caused a reduction in tumor volume, but had no effect on final incidence or number of mammary tumors. Combined modality treatment resulted in a significant reduction in the volume of existing tumors and suppressed the enhanced occurrence of additional tumors observed when only radiation alone was administered. CONCLUSION: The findings of this study indicate that in the context of fractionated, high dose radiation treatment of established mammary cancers, tamoxifen may reduce the likelihood of subsequent tumor development and by so doing prove a helpful simultaneous conjoint adjuvant treatment to post-operative irradiation. PMID- 8482636 TI - Nicotinamide exerts different acute effects on microcirculatory function and tissue oxygenation in rat tumors. AB - PURPOSE: Nicotinamide has been reported to preferentially radiosensitize tumor tissue, supposedly through a reduction in tumor hypoxia. This may occur as a result of nicotinamide-induced changes in tumor blood flow and therefore the present study was undertaken to evaluate the effect of nicotinamide on circulatory parameters in skeletal muscle and tumor tissue (subcutaneously implanted DS-sarcomas) of the rat. METHODS AND MATERIALS: Mean arterial blood pressure (measured in the common carotid artery using a pressure transducer) and red blood cell flux (as measured by laser Doppler flowmetry) were continuously monitored for 120 min following a single intraperitoneal application of nicotinamide (500 mg/kg). An arterial blood pressure/laser Doppler flux ratio was estimated for tumor and muscle tissue. RESULTS: Nicotinamide significantly reduced the mean arterial blood pressure to a minimum value 25% below the pretreatment value 20 min after the commencement of drug administration, with partial recovery thereafter. Red blood cell flux through tumor tissue, following an initial rapid decrease, rose steadily to values 34% above those measured in control animals at t = 60 min, while the arterial blood pressure/laser Doppler flux ratio in tumor tissue fell to values 34% below those of control animals. In skeletal muscle similar trends were seen although the changes were not of the same extent as those seen in tumor tissue. Tumor pO2 was measured 60 min following i.p. application of nicotinamide using polarographic needle electrodes. Despite the significant increase in blood flow following nicotinamide, no significant difference was seen between pO2 histograms obtained in tumors in nicotinamide-treated and control animals. CONCLUSION: These findings suggest that nicotinamide preferentially improves tumor microcirculatory function and effectuates a decrease in the arterial blood pressure/laser Doppler flux ratio within tumor tissue, effects which reach their maximum approximately 60 min following nicotinamide administration. PMID- 8482637 TI - Uptake of pulmonary surfactant protein C into adult rat lung lamellar bodies. AB - Previous studies have provided evidence that a large proportion of secreted surfactant lipids is taken up from the alveolar air space by type II cells, incorporated into lamellar bodies, and resecreted. Our goal was to characterize the clearance of exogenously administered recombinant surfactant protein C (SP-C) and to determine if SP-C is taken up by type II cells and incorporated into lamellar bodies. SP-C was radiolabeled by alkylation with [3H]iodoacetic acid and retained its ability to enhance phospholipid adsorption to an air-liquid interface. A mixture of 100 micrograms phospholipid radiolabeled with [14C]dipalmitoylphosphatidylcholine and 10 micrograms SP-C was instilled into the lungs of spontaneously breathing anesthetized adult rats. At later times, the lungs were lavaged and subcellular organelles were isolated. The radioactivity of both phospholipids and SP-C (expressed as disintegrations per minute per microgram phospholipid) in lamellar body fractions increased up to 4 h postinstillation and began to decline after approximately 4 h. The results of this study suggest that SP-C and dipalmitoylphosphatidylcholine are taken up promptly from the alveolar air space and are incorporated into lamellar bodies with time courses that do not differ greatly. PMID- 8482638 TI - Lack of heart rate variation between morning and afternoon exercise testing in coronary artery disease patients. AB - The purpose of this study was to investigate cardiovascular [heart rate (HR), blood pressures, rate-pressure product (RPP)], physiological (oxygen uptake), and metabolic (blood plasma lactic acid concentration) responses during symptom limited graded exercise testing (SL-GXT) during early morning and late afternoon hours in an unmedicated, regularly exercising, coronary artery disease population. Subjects, males ages 41-71 yr (n = 11), underwent SL-GXT via cycle ergometry at 8:30 A.M. and 4:30 P.M. HR, systolic blood pressure, diastolic blood pressure, and RPP were evaluated at rest and at submaximal and peak work. Oxygen uptake and rate of perceived exertion were also determined at submaximal and peak power output, with blood plasma lactic acid concentration measured at peak work. Data, analyzed by the paired t test, failed to demonstrate any significant variation in HR, systolic blood pressure, diastolic blood pressure, RPP, or blood plasma lactic acid responses during exercise at the two points used. Oxygen uptake did not significantly change at any submaximal intensity. Thus SL-GXT results obtained at early morning (8:30 A.M.) and late afternoon (4:30 P.M.) are a reproducible, reliable means of prescribing exercise HR and work intensities. PMID- 8482639 TI - Influence of detergent aerosol on lung microvascular permeability. AB - Noncardiogenic edema fluid often contains high levels of plasma proteins, which may inhibit the function of the lung surfactant complex and thus decrease interstitial hydrostatic pressures. We questioned whether, in the awake and standing animal, displacement of the alveolar surface lining would alter the permeability of the thin and sparsely supported pulmonary capillaries. Sheep prepared with lung lymph fistulae were given an aerosolized detergent (Det) to displace the lung surfactant complex. After the sheep were given Det, protein flux was significantly increased (P < 0.05). To validate the suggested permeability increase, pulmonary vein occluders were surgically implanted and experiments repeated with pulmonary arterial pressures elevated 10 mmHg above baseline. After 2 h of elevated pulmonary arterial pressure, lung lymph increased fivefold. At this time, lymph-to-plasma total protein concentration ratios for air and saline-plus-ethanol vehicle were significantly lower (P < 0.01) than baseline ratios (0.26 +/- 0.06 and 0.34 +/- 0.07, respectively). No significant difference could be shown in lymph-to-plasma ratios after the sheep were given Det. We conclude that disruption of the alveolar lining can cause a detectable increase in protein flux due, in part, to an increase in microvascular permeability. PMID- 8482640 TI - Validity of the esophageal balloon technique at high frequencies. AB - The reliability of the esophageal balloon technique in measuring high-frequency changes in pleural pressure (Ppl) was investigated in six normal subjects by studying the amplitude ratio (A) and phase angle (phi) of esophageal (Pes) and mouth (Pm) pressures during airway occlusion and while pseudorandom pressure variations (2-32 Hz) were applied to the chest. The measurements were made with a common esophageal balloon-catheter system connected to a high-impedance piezoresistive transducer. When the cheeks were firmly supported, A averaged 1.08 +/- 0.063 at 2 Hz and 1.06 +/- 0.11 at 32 Hz. Pes increasingly led Pm with increasing frequency, and phi averaged 20.8 +/- 4.0 degrees at 32 Hz. Washing the airways with 80% He-20% O2 reduced phi by 50%. When the cheeks were not supported, A exhibited a strong positive frequency dependence, averaging 1.71 +/- 0.34 at 32 Hz, whereas phi increased much faster below 20 Hz and tended to decrease afterward. Because the esophageal transfer function Pes/Ppl = (Pes/Pm)/(Ppl/Pm), we could estimate Pes/Ppl by computing for individual subjects the pressure difference between the pleura and the mouth based on the lung and upper airway wall properties that were measured separately. The results suggest that the ratio of Pes and Ppl remains close to unity from 2 to 32 Hz, but Pes lags slightly behind Ppl (phi equals about -7 degrees at 32 Hz). PMID- 8482641 TI - Total respiratory input impedance with the upper airway wall shunt minimized. AB - Respiratory impedances (Zrs) measured with the cheeks manually supported (Zsc) demonstrate an antiresonance (AR) at approximately 170 Hz, whereas those measured with the head generator (Zhg) have an AR at significantly lower frequencies (150 Hz). The differences in the AR between methods were previously attributed to upper airway wall (UAW) shunting in Zsc, and Zhg was believed to represent shunt free impedance. To test this hypothesis, we measured four independent estimates of Zrs (4-256 Hz) in five healthy adults. Applying the oscillations at the mouth, we measured Zrs with the cheeks unsupported (Zuc) and when the subject's head and neck were enclosed in a rigid chamber completely filled with water (Zwa). We also measured Zhg with the oscillations applied around the head. Because water is incompressible, Zwa should minimize UAW shunt if not completely eliminate it. There were no significant differences in any of the AR features (e.g., location and bandwidth) of Zuc, Zsc, and Zwa. Conversely, all AR features of Zwa and Zhg were significantly different. To assess wall motion during both forms of oscillations (i.e., applied at the mouth and around the head), we measured two UAW local impedances by use of accelerometers placed on the cheeks (Zch) and submental (Zsm) region. Above 40 Hz, Zch and Zsm estimates were significantly dependent on the forcing method. Furthermore, Zch and Zsm made with the standard oscillations were consistent with the lumped UAW impedances measured with a head plethysmograph, whereas those made with the oscillations around the head were not. Therefore we conclude that, at > 32 Hz, Zsc more closely represents shunt free impedance than does Zhg and hence should be preferred when Zrs are measured. PMID- 8482642 TI - Weight-training-induced attenuation of the circulatory response of older males to weight lifting. AB - We examined the effects of 12 wk of dynamic strength training on the heart rate (HR) and blood pressure of older male subjects during 10 repetitions of single arm curl and single- and double-leg press at 60 and 80% of both the pre- and posttraining maximum capacities and during single maximum lifts (1 RM). The circulatory responses were greater at 80% of 1 RM than at 60% and increased with active muscle mass. After training, the 1 RMs increased by 24 (legs) to 54% (arms) and there was a marked attenuation of HR and arterial pressure during exercise when subjects lifted the same absolute load. Greatest reductions in HR (108 +/- 4 to 94 +/- 2 beats/min), systolic blood pressure (BPs, 247 +/- 14 to 206 +/- 9 Torr), diastolic pressure (156 +/- 9 to 116 +/- 5 Torr), mean arterial pressure (143 +/- 6 to 131 +/- 5 Torr), and rate-pressure product (268 +/- 22 to 196 +/- 12 HR.BPs/100) occurred during double-leg press at 80% of the pretraining 1 RM. After training, during lifting at 60, 80, and 100% of the posttraining 1 RMs, the HRs and arterial pressures were the same as those during pretraining testing when the same relative, but lighter, absolute loads were used. These observations are consistent with a significant part of the circulatory response to weight lifting being mediated by a feedforward "central command" mechanism coupled to the relative intensity rather than to the absolute level of force. PMID- 8482643 TI - Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling. AB - We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2-5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482644 TI - Centrally driven slow oscillating potential of extrathoracic trachea. AB - Spontaneous electrical activity of extrathoracic trachea was recorded along with force developed by tracheal smooth muscle and phrenic nerve activity in decerebrated, paralyzed, and artificially ventilated dogs with pneumothorax. The tracheal electrical activity exhibited slow oscillating potentials that were coupled with spontaneous phasic contraction of trachea. Both rhythmic changes were synchronous with central respiratory rhythm represented by phrenic burst, independent of the respirator's rhythm. The dominant component of the slow oscillating potentials consisted of sinusoidal waves with large amplitude that occurred shortly after cessation of phrenic burst, i.e., in the postinspiratory phase. The concomitant small change in the slow oscillating potentials began in the late inspiratory phase just before the initiation of the tracheal contraction. This phase relationship was preserved after removal of intrathoracic vagal afferents from lungs. Such slow oscillating potentials were also observed during lung collapse produced by disconnecting the tube attached to the respirator. Transection of recurrent laryngeal nerves abolished the slow oscillating potentials. These results indicate that the slow oscillating potentials of the extrathoracic trachea are generated by a physiological process associated with the central respiratory rhythm. The dominant component of the slow oscillating potentials occurs in the postinspiratory phase. PMID- 8482645 TI - Breathing periodicity in intact and carotid body-denervated ponies during normoxia and chronic hypoxia. AB - Periodic oscillations in pulmonary ventilation (VI), tidal volume (VT), and inspiratory and expiratory times (TI and TE) were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40-50 Torr) in awake intact (n = 8) and carotid body-denervated (CBD; n = 8) ponies. Periodic oscillations were identified by fast-Fourier transformation of breath-by-breath data and quantitated by determining the power ratio of significant periodic oscillations to total power of data sequence. Periodic oscillations of 0.063 0.500 cycles/breath were observed in all parameters during both normoxia and hypoxia. During normoxia, CBD accentuated periodicity of VT (P < 0.02) and VI (P < 0.01) but did not change TI or TE periodicity (P > 0.05). These findings suggest that carotid chemoreceptors serve to stabilize breathing (i.e., decrease periodicity) during normoxia, conceivably because of their shorter response time compared with that of central chemoreceptors. During certain periods of hypoxia, periodicity of VT and VI was significantly (P < 0.05) increased in intact ponies. The response to hypoxia in CBD ponies was variable, with VI periodicity significantly (P < 0.05) increasing, decreasing, or unchanging. Because some CBD ponies significantly changed their periodicity during hypoxia compared with normoxia, we conclude that carotid chemoreceptors are not requisite for hypoxia induced changes in periodic breathing. In addition, our observations in both groups of ponies during normoxia and hypoxia suggest that multiple mechanisms may lead to periodic oscillations in breathing. PMID- 8482646 TI - Effect of pulmonary blood flow on measurements of respiratory mechanics using the interrupter technique. AB - The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary arterial pressure, and left atrial pressure is unclear. Conventional methods for the measurement of respiratory mechanics model the respiratory system as a single compartment, which may not adequately represent the respiratory system in a diseased state. The interrupter technique models the respiratory system as two compartments, with the "flow resistance" of the conducting airways and chest wall (Raw) considered separately from Pdif, a measure of the viscoelastic properties of the lung and chest wall, together with any pendelluft present. The respiratory mechanics of 15 infants in the first year of life were studied during cardiac catheterization with the use of conventional methods and the interrupter technique. The infants had a PBF-to-systemic blood flow ratio ranging from 0.6 to 4.0:1. The specific dynamic compliance of the respiratory system was not related to the PBF; however, there was a significant relationship between PBF and the total resistance of the respiratory system (Rrs) [analysis of variance (ANOVA) F = 5.69, P < 0.05], Raw (ANOVA, F = 12.30, P < 0.01), and Pdif (ANOVA, F = 3.79, P < 0.05). Rrs increased significantly with an increase in mean left atrial pressure (ANOVA, F = 6.92, P < 0.05); however, dynamic compliance, Raw, and Pdif did not. These results suggest that the relationship between Rrs and PBF is due an increase in the resistive properties of the conducting airways and tissue components. PMID- 8482647 TI - Impact of frequency range and input impedance on airway-tissue separation implied from transfer impedance. AB - In humans, application of the DuBois (DuBois et al. J. Appl. Physiol. 8: 587-594, 1956) six-element model to respiratory transfer impedance (Ztr) data has been proposed as a means to noninvasively estimate airway and tissue properties. This approach requires prior knowledge of alveolar gas compressibility (Cg). With input impedance (Zin), prior knowledge of Cg is not required, but the data do not support a reliable separation of airway from tissue properties. In this study, we investigated the separation of airway and tissue properties when Ztr and Zin data are measured and analyzed simultaneously over a larger frequency range than usual. In 10 healthy adults, we measured Ztr and Zin from 2 to 64 Hz. Zin was measured using both the standard approach with oscillations directly into the airway opening (Zst) and the head generator approach (Zhg) with oscillations applied around the head. With Ztr data alone, we found that the airway resistance and inertance estimates were reliable with only 2- to 32-Hz data and were unaffected by including the additional 32- to 64-Hz data. Conversely, the estimates of tissue resistance and inertance were highly unreliable unless the 32 to 64-Hz data are included. Because of enhanced sensitivity of Ztr to Cg from 32 to 64 Hz, inaccuracies in the assigned Cg will distort the estimated tissue but not airway properties. The Ztr-based parameters predicted Zhg data far better than Zst data, which is consistent with Zhg data being less influenced by upper airway shunting over this frequency range. There was no apparent advantage to combining Ztr and Zhg data during parameter estimation. With Cg unfixed, the estimated Cg was 50-100% higher than expected from an independent measurement of functional residual capacity. These results confirm that Ztr alone can provide a reliable distinction of lumped respiratory airway and tissue properties that are little influenced by upper airway wall shunting but only if 2- to 64-Hz data are analyzed. This distinction, however, requires an accurate prior measurement of Cg, and this requirement cannot be removed by combining Ztr and Zin data. PMID- 8482648 TI - Gas uptake from an unventilated area of lung: computer model of absorption atelectasis. AB - A computer model of gas uptake from an area of nonventilated lung, such as a pulmonary lobe with an occluded bronchus or an alveolus with an occluded airway, is presented. Previous analyses have assumed that when an inert gas is present, equilibration of O2 and CO2 with mixed venous blood is sufficiently rapid to be treated as instantaneous. This is valid for insoluble gases such as N2 or He when the fractional concentration of inspired O2 (FIO2) is < or = 0.6 but is invalid for a relatively soluble gas such as N2O. When a mixture of O2 and an inert gas is breathed, the time for an area of unventilated lung to collapse depends on the solubility of the inert gas and FIO2. When the solubility is low (N2 or He), collapse takes longer than when 100% O2 is breathed, and the lower the FIO2 the longer the time to collapse. When the gas is more soluble (N2O) and FIO2 is > 0.3, collapse is more rapid than when 100% O2 is breathed. PMID- 8482649 TI - Effect of inhaled lyso-platelet-activating factor on airway microvascular leakage in the guinea pig. AB - Lyso-platelet-activating factor (PAF), the precursor and metabolite of PAF, is considered inactive, although it may be converted to PAF by airway cells. We have investigated the effects of inhaled lyso-PAF on bronchoconstriction and airway microvascular leakage in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after inhalation of lyso-PAF (0.3, 1, and 3 mM; 30 breaths) followed by measurement of extravasation of intravenous Evans blue dye into airway tissues, which was used as an index of airway microvascular leakage. Inhaled lyso-PAF caused an increase in RL and leakage of dye at all airway levels in a dose-dependent fashion, but intravenous lyso-PAF (0.25 mg/kg) had no airway effect. The maximum dose of inhaled lyso-PAF increased RL significantly by approximately 200%. The amount of extravasation of dye induced was 96 +/- 4 (SE) ng/mg of tissue in trachea, 77 +/- 8 ng/mg in main bronchi, and 65 +/- 7 and 25 +/- 1 ng/mg in proximal and distal intrapulmonary airways respectively; these values were all significantly higher (P < 0.01) than control values. These responses were completely abolished by a specific PAF-receptor antagonist WEB 2086 (2 mg/kg iv). Our results show that inhaled lyso-PAF is potent in increasing airway microvascular leakage. The effects of lyso-PAF may result from its metabolic transformation to PAF by lyso-PAF:acetyl-CoA acetyltransferase in the airway. PMID- 8482650 TI - Arterial blood pressure responses to graded transient arousal from sleep in normal humans. AB - During obstructive sleep apnea, transient arousal at the resumption of breathing is coincident with a substantial rise in blood pressure. To assess the hemodynamic effect of arousal alone, 149 transient stimuli were administered to five normal subjects. Two electroencephalograms (EEG), an electrooculogram, a submental electromyogram (EMG), and beat-to-beat blood pressure (Finapres, Ohmeda) were recorded in all subjects. Stimulus length was varied to produce a range of cortical EEG arousals that were graded as follows: 0, no increase in high-frequency EEG or EMG; 1, increased high-frequency EEG and/or EMG for < 10 s; 2, increased high-frequency EEG and/or EMG for > 10 s. Overall, compared with control values, average systolic pressure rose [nonrapid-eye-movement (NREM) sleep 10.0 +/- 7.69 (SD) mmHg; rapid-eye-movement (REM) sleep 6.0 +/- 6.73 mmHg] and average diastolic pressure rose (NREM sleep 6.1 +/- 4.43 mmHg; REM sleep 3.7 +/- 3.02 mmHg) over the 10 s following the stimulus (NREM sleep, P < 0.0001; REM sleep, P < 0.002). During NREM sleep, there was a trend toward larger blood pressure rises at larger grades of arousal (systolic: r = 0.22, 95% confidence interval 0.02-0.40; diastolic: r = 0.48, 95% confidence interval 0.31-0.62). The average blood pressure rise in response to the grade 2 arousals was approximately 75% of that during obstructive sleep apnea. Arousal stimuli that did not cause EEG arousal still produced a blood pressure rise (mean systolic rise 8.6 +/- 7.0 mmHg, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482651 TI - Properties of motor units after immobilization of cat peroneus longus muscle. AB - Changes in contractile properties of cat peroneus longus motor units were studied 2, 5, and 8 wk after selective immobilization of this muscle, which was achieved by fixing the distal tendon of the peroneus longus to the fibula either at the muscle minimal physiological length ("short" length) or at the length for a 90 degree ankle joint ("neutral" length). In each muscle, 75-90% of the units [slow (S), fast resistant to fatigue (FR), fast intermediate (FI), and fast fatigable (FF)] were studied. Immobilization elicited a permanent decrease in tetanic force developed by single motor units, which was larger for resistant-to-fatigue units (S, FR). In most instances this decrease was not related to the immobilization length. In all units, twitch contraction and half-relaxation times underwent a transient increase, the extent and time course of which were influenced by immobilization length. The relationship between the frequency of motor units activation and the ratio of unfused to maximal tetanic force was studied. For fast units, there was a transient shift of the relation toward low frequencies after 2 and 5 wk of immobilization at neutral and short length, respectively. PMID- 8482652 TI - Embolus size affects gas exchange in canine autologous blood clot pulmonary embolism. AB - Embolic pulmonary hypertension is associated with alterations in gas exchange of variable severity, which we hypothesized to be related to embolus size. We therefore examined the effects of different-size autologous blood clot embolization on pulmonary arterial pressure-cardiac output relationships (Ppa/Q) and on the distribution of ventilation-perfusion ratios (VA/Q) in 18 intact anesthetized and ventilated (inspired fraction of O2 0.4) dogs. Multipoint Ppa/Q plots were generated by a manipulation of venous return before and 60 min after sufficient amounts of small (1 mm, n = 6 dogs), medium (5 mm, n = 6 dogs), or large (10 mm, n = 6 dogs) clots to increase Ppa to 50 mmHg. The distribution of VA/Q was determined by the multiple inert gas elimination technique at the same intermediate Q in each of these experimental conditions. All three sizes of emboli resulted in an 82-92% mean angiographic pulmonary vascular obstruction and increased both the extrapolated pressure intercepts and the slopes of the linear Ppa/Q plots. Gas exchange was altered the most after large clots, which were associated with lower arterial pH, higher physiological and inert gas dead spaces, higher dispersion of ventilation, and also lower mean VA/Q of perfusion distributions. In contrast, inert gas dead space was decreased after small clots. We conclude that, in autologous blood clot embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size but that gas exchange is affected differently, mainly in high-VA/Q regions and most often after the largest clots. PMID- 8482653 TI - Myosin and troponin changes in rat soleus muscle after hindlimb suspension. AB - We examined the myosin heavy-chain (MHC), troponin T (TnT), and troponin I (TnI) isoform composition in the rat soleus muscle after 21 days of hindlimb suspension using electrophoretic and immunoblotting analysis with specific monoclonal antibodies. The suspended soleus showed a shift in the MHC isoform distribution with a marked increase (from 1.0 to 33%) in the relative amount of type IIa and IIx MHC and a corresponding decrease in type I MHC. However, type IIb MHC, which represents a major component in fast-twitch muscles, was not detected in suspended soleus muscles. TnT and TnI isoform composition was also changed with the appearance of fast-type TnI and TnT bands. However, a high-mobility TnT band, which represents a major component in fast-twitch muscles, was not expressed in suspended soleus. These isoform transitions may be related to the increased maximal velocity of shortening and higher calcium sensitivity previously reported in the rat soleus after hindlimb suspension. PMID- 8482654 TI - Dissipation of metabolic heat in the horse during exercise. AB - Horses were exercised at 40, 65, and 90% of their maximum O2 uptake (VO2max) until moderately fatigued (approximately 38, 15, and 9 min, respectively) to assess heat loss through different routes. Approximately 4,232, 3,195, and 2,333 kcal of heat were generated in response to exercise at these intensities. Of this, approximately 7, 16, and 20% remained as stored heat 30 min postexercise. Respiratory heat loss, estimated from the temperature difference between blood in the pulmonary and carotid arteries and the cardiac output, was estimated to be 30, 19, and 23% of the heat produced during exercise at the three intensities. The kinetics of the increases in muscle and blood temperature were similar, with the greatest change in temperature occurring in muscle (+3.8, 5.2, and 6.1 degrees C after exercise at 40, 65, and 90% of VO2max, respectively). The temperature of blood in the superficial thoracic vein was approximately 2 degrees C below that of arterial blood at rest. This difference had increased to approximately 3 degrees C during the last minute of exercise. The rate of sweating at sites on the back and neck increased with exercise intensity to a common peak of approximately 40 ml.m-2.min-1. If complete evaporation had occurred, water loss in response to exercise (estimated to be 12, 10, and 7.7 liters for the different intensities of exercise) greatly surpassed that required for dissipation of the metabolic heat load. PMID- 8482655 TI - Pulmonary interstitial pressure in intact in situ lung: transition to interstitial edema. AB - In anesthetized rabbits (n = 25) subject to slow intravenous saline loading (0.4 ml.min-1.kg-1) for 3 h, we measured pulmonary interstitial pressure (Pip) in intact in situ lungs with glass micropipettes inserted directly into the lung parenchyma via a "pleural window." Measurements were done in apneic animals at the end-expiratory volume with O2 delivered in the trachea. Pip was -10 +/- 1.5 (SD) cmH2O in control and increased to 0.6 +/- 3.8 and 5.7 +/- 3.3 cmH2O at 66 and 180 min, respectively. The wet-to-dry weight ratio (W/D) of the lung was 5.04 +/- 0.2 in the control group and 5.34 +/- 0.7 at 180 min (+6%); the corresponding W/D for intercostal muscles were 3.25 +/- 0.03 and 4.19 +/- 0.5 (+28%). Pulmonary interstitial compliance was 0.47 ml.mmHg-1.100 g wet wt-1. Pulmonary arterial and left atrial pressures were 18.4 +/- 2 and 3 +/- 1 cmH2O in control and increased to 19.5 +/- 2.9 and 4.6 +/- 1.7 cmH2O at 180 min, respectively. Aortic flow (cardiac output) increased from 103 +/- 35 to 131 +/- 26 ml/min; pulmonary resistance fell from 0.17 +/- 0.06 to 0.14 +/- 0.05 cmH2O.min.ml-1 (-18%), suggesting that the increase in Pip did not limit blood flow. The pulmonary capillary-to-interstitium filtration pressure gradient decreased sharply from a control value of 10 cmH2O to 0 cmH2O within 60 min because of the increase in Pip and remained unchanged for < or = 180 min. Data suggest that the pulmonary interstitial matrix can withstand fluid pressures above atmospheric, preventing the development of pulmonary alveolar flooding. PMID- 8482656 TI - Failure of vasodilator administration to increase blood flow to the fatiguing diaphragm. AB - Recent studies have suggested that coronary and limb muscle vessels do not maximally vasodilate under conditions in which cardiac and limb muscle contractile function is dependent on the level of blood flow but, rather, maintain a "vasodilator reserve." If a vasodilator reserve is also present in the fatiguing diaphragm, it may be possible to augment flow to this muscle with vasodilator administration, improving muscle function. The purpose of the present study was therefore to examine the effect of administration of a potent vasodilator, nitroprusside, on the blood flow and contractile function of the fatiguing diaphragm. Studies were performed using an in situ canine diaphragmatic strip preparation that permitted direct measurement of force and blood flow; cardiac output was monitored with a thermodilution catheter. The effects of nitroprusside were examined with the diaphragm rhythmically contracting in response to both subfatiguing and fatiguing stimulation paradigms. For both contraction paradigms, nitroprusside infusions elicited appreciable increases in cardiac output. Nitroprusside infusions also produced significant increases in diaphragmatic blood flow during subfatiguing diaphragmatic contractions but had no effect on flow during fatiguing contractions. Nitroprusside also had no effect on the rate of diaphragmatic fatigue. These data suggest that, under the conditions examined, the diaphragm exhausts its vasodilator reserve during the development of fatigue and vasodilator administration has no appreciable effect on diaphragm blood flow and function. Moreover, although vasodilator drugs with actions similar to nitroprusside are used clinically to augment flow to vital organs, our data would indicate that these drugs have no functionally significant effect on blood flow to the fatiguing diaphragm. PMID- 8482657 TI - Effects of intraphrenic injection of potassium on diaphragm activation. AB - The purpose of the present study was to determine whether potassium, injected into the arterial supply of the diaphragm, would reflexly alter efferent diaphragmatic motor outflow and systemic arterial pressure. Studies were performed using in situ canine diaphragm muscle strips in which the inferior phrenic artery and vein were cannulated and all other sources of strip blood flow were ligated. Injection of potassium (0.1 meq) into the inferior phrenic artery elicited a small transient (1-2 breaths) decrease in the peak strip tension developed during spontaneous muscle contractions, in peak integrated strip electromyographic (EMG) activity, and in the peak integrated EMG activity of the contralateral hemidiaphragm. This was followed by a more pronounced and more sustained increase in each of these parameters as well as an increase in systemic arterial pressure. This latter excitatory response was qualitatively similar to that induced by the injection of capsaicin (5 and 25 micrograms) into the phrenic artery. Section of the left phrenic nerve abolished the effects of intra-arterial potassium and capsaicin on systemic arterial pressure and right hemidiaphragm EMG activity. These data support the existence of a potent excitatory phrenic-to phrenic reflex that can be activated by potassium injection into the diaphragm. Activation of this pathway increases diaphragm motor activation and augments systemic arterial pressure. PMID- 8482658 TI - Bilateral deficit is larger for step than for ramp isometric contractions. AB - The force produced by a muscle group during a maximum effort bilateral task has been reported to be less than that produced during a maximum effort unilateral task. It was hypothesized that if decreased activation of primarily fast motor units is responsible for this bilateral deficit, 1) the bilateral deficit would be larger in step than in ramp isometric contractions and 2) the rate of torque generation in step contractions would be slower in bilateral than in unilateral tasks. Twelve healthy male subjects performed unilateral and bilateral isometric knee joint extension tasks in which maximum torque was generated under ramp and step conditions. The maximum torques produced in the bilateral tasks were 17.0 and 24.6% less than those produced in the unilateral tasks during the ramp and step conditions, respectively (both P < 0.001). The bilateral torque deficit for the step condition was significantly greater than that for the ramp condition (P = 0.012). The rate of torque generation in the step condition was 19.7% slower in the bilateral than in the unilateral task (P = 0.010). Thus the results from these torque measurements support the notion that decreased activation of primarily fast motor units may be responsible for the bilateral deficit. PMID- 8482659 TI - Evaluation of various models for respiratory inductance plethysmography calibration. AB - We evaluated one nonlinear and two linear models of the ventilatory system while calibrating the respiratory inductance plethysmograph (RIP) against a pneumotachometer. A calibration method involving voluntary varying rib cage and abdominal contributions to tidal volume in a single body position was utilized. The influence on accuracy of the choice of respiratory phase during calibration was assessed. Both tidal and intratidal volumes were evaluated. Ten adults with no history of respiratory disorders went through RIP calibration and validation in the sitting and supine positions. A linear calibration model, relating lung volume changes from the start of inspiration or expiration to rib cage and abdominal excursions from initiation of respiratory motion, had the best accuracy. The choice of respiratory phase for calibration did not affect accuracy. RIP generally underestimated lung volume at the start of inspiration and overestimated lung volume at the end of inspiration. RIP was more accurate in the supine than the sitting position, probably because of limited spine flexion in the supine position. PMID- 8482660 TI - Effects of long-term continuous respiratory resistive loading on rat diaphragm function and structure. AB - The effects of long-term (24- to 28-wk) continuous respiratory resistive loading on diaphragm mass, contractility, fatigue, and fiber types were studied in male rats. Increased respiratory resistance was produced by extratracheal banding, and results were compared with sham-operated pair-fed controls. At the time the animals were killed, banded tracheal segment internal diameter was reduced by 57% of control values. Diaphragm surface area and muscle mass (normalized for body mass) increased by 19% of control values. Isometric diaphragm contractility and fatigue resistance indexes were measured using an in vitro diaphragm costal strip preparation at 37 degrees C. Twitch and tetanic stimulations were evoked using direct stimulation. Compared with controls, baseline tensions (normalized for diaphragm cross-sectional area) were significantly decreased at low frequencies. Fatigue resistance (endurance) indexes were significantly increased at all frequencies. These findings were consistent with observed increases in number and cross-sectional area of type I (low-tension high-endurance) fibers. We conclude that the diaphragm adapts to chronic long-term resistive loads by sacrificing peak tensions for an increase in endurance capacity. PMID- 8482661 TI - Renin-angiotensin system stimulates respiration during acute hypotension but not during hypercapnia. AB - We reported that intravenous infusion of angiotensin II (ANG II) stimulated ventilation (VE) in conscious dogs. Other studies in our laboratory have demonstrated that increases in respiration occurred in association with activation of the renin-angiotensin system during acute hypotension and during hypercapnia. Therefore, in conscious dogs (n = 5), we examined the effects of ANG II receptor blockade with intravenous saralasin (0.5 micrograms.kg-1.min-1) on respiratory responses during progressive nitroprusside-induced hypotension and during the ventilatory response to increased inspired fraction of CO2 (VRC). During hypotension (mean arterial pressure decreased approximately 20%) combined with ANG II receptor blockade, VE, heart rate, and arginine vasopressin increases were attenuated compared within unblocked studies. With ANG II receptor blockade during hypotension, alveolar ventilation and arterial PCO2 (PaCO2) were unchanged, which contrasted with a doubling of alveolar ventilation and a decrease of 4.8 +/- 1 Torr in PaCO2 in unblocked studies. During hypercapnia, the slope of the VRC was not affected by ANG II receptor blockade, but with 6.5% inspired CO2 fraction, VE and PaCO2 were lower than in unblocked studies. These results indicated that ANG II contributed to the respiratory response to a modest hypotension but did not affect respiratory sensitivity to CO2. PMID- 8482662 TI - Selective brain cooling is affected by wearing headgear during exercise. AB - The purpose of this work is to relate the concept of selective brain cooling (SBC) during exercise to heat loss from the head while either bare or covered. During hyperthermia, SBC is considered to occur if tympanic temperature (Tty) is lower than esophageal temperature (Tes). In experiment I the head heat loss was measured with and without headgear. Each of four subjects took part in three sessions of exercise on a cycle ergometer. The face was cooled to simulate outdoor conditions. The first session (no headgear) served as control for the two following sessions in which a headband and a woolen cap were worn. Evaporative and radiative-convective heat loss were monitored from the head. Wearing a cap significantly reduced the heat loss from the head compared with the control condition. During the headband session the heat loss was not significantly lower than the control values. Tty, Tes, and head skin temperatures (T(sk)) were also recorded. Tty was significantly lower (-0.55 +/- 0.15 degrees C) than Tes at the end of exercise (150-W exercise load) when no headgear was worn. During headgear sessions, Tty was no longer significantly lower than Tes, either during the headband (-0.15 +/- 0.31 degrees C) or during the cap session (-0.30 +/- 0.13 degrees C). In experiment II the influence of wearing headgear on temperature regulation was studied. Hand skin blood flow, hand T(sk), and heat loss from the hand were recorded in addition to the variables monitored in experiment I. Wearing headgear elevated Tty and peripheral vasomotor responses, whereas Tes evolved in the opposite direction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482663 TI - Body fluid compartments, renal blood flow, and hormones at 6,000 m in normal subjects. AB - We previously described a syndrome of congestive heart failure occurring in healthy young men at extreme altitude (Anand et al. Lancet 335: 561-565, 1990). The pathogenesis of this condition is unclear. We therefore measured body fluid compartments, renal blood flow, and a variety of plasma hormones in 10 asymptomatic young men staying above 6,000 m for > 10 wk and compared the results with controls at sea level. Body compartments were measured with isotope dilution techniques and renal blood flow with o-[125I]iodohippurate sodium. There was a marked expansion of all the fluid spaces: total body sodium was 14% above normal (P < 0.05), total body water was 18% above normal (P < 0.05), plasma volume was 33% above normal (P < 0.05), and blood volume was 84.5% above normal (P < 0.001). The effective renal plasma flow was lower than normal by 55% (P < 0.001), but the reduction in the effective renal blood flow was 37% below normal (P < 0.001) because the hematocrit was high (41.6% above normal). Plasma norepinephrine was nearly 3 times normal (P < 0.01), cortisol 3 times normal (P < 0.001), and growth hormone 18 times normal (P < 0.01). Aldosterone was twice normal (P < 0.03). Plasma epinephrine, atrial natriuretic peptide, and plasma renin activity were unchanged. The degree of fluid retention in these normal subjects was similar to that in patients with severe untreated congestive heart failure (Anand et al. Circulation 80: 299-305, 1989), whereas sodium retention and reduction in effective renal blood flow were less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482664 TI - Surfactant treatment effects on alveolar type II cell morphology in rabbit lungs. AB - The effects of exogenous surfactant administration on alveolar type II cells and the lung parenchyma were examined in adult rabbits. Natural surfactant was instilled into the left lobe of New Zealand White rabbits while the right lobe served as the control. Four hours post-instillation, the lungs were fixed by vascular perfusion. Surfactant instillation did not change alveolar type II cell size but was associated with a significant reduction in the volume fraction of lamellar bodies in type II cells (20.4% in control lobes compared with 11.9% in surfactant-treated lobes). The size distribution of lamellar body profiles was different in surfactant-treated lobes compared with control lobes, with a significant decrease in lamellar bodies > 0.8 microns in diameter and a twofold increase in lamellar bodies 0.2-0.4 microns in diameter. Composite body profile number was also increased by 87% (P < 0.05) after instillation of surfactant compared with control. Saline instillation decreased lamellar body volume fraction in type II cells but three times less than surfactant instillation. These observations are consistent with a strong stimulus for secretion of endogenous surfactant 4 h after surfactant instillation in normal adult rabbit lungs, whereas the increase in composite bodies is consistent with new lamellar body formation, probably from both de novo synthesized and exogenous natural rabbit surfactant. These observations confirm that the secretory and synthetic processes of alveolar type II cells are significantly affected by exogenous surfactant instillation. PMID- 8482665 TI - Heat stress does not modify lactate exchange and removal abilities during recovery from short exercise. AB - Arterial and femoral venous lactate concentrations were measured before, during, and after short intermittent exercise (55-118% of maximal O2 consumption) in thermoneutral (N, 25 degrees C, 10.5 Torr) and hot (H, 45 degrees C, 17.5 Torr) conditions. The thermal load induced significantly higher heart rate and rectal temperature in H relative to N. All the arterial lactate (La) recovery curves were fitted to an equation containing two exponential time functions of the form La(t) = La(0) + A1a(1 - e-gamma 1at) + A2a(1 - e-gamma 2at) where the velocity constants gamma 1a and gamma 2a are the body's overall ability to exchange and remove lactate after exercise, respectively, and t is time. There was no significant difference in these constants, regardless of thermal conditions. The arterial lactate concentration at the end of exercise, the peak lactate concentration during recovery, the amplitudes A1a and A2a of the biexponential function, and the arteriofemoral venous lactate concentration difference during recovery were not significantly different in H relative to N. However, measured and computed arterial lactate concentrations during recovery, especially at the end of the tests, were higher in H (P < 0.04). The more elevated lactate concentrations in H at rest at the end of recovery denote a higher basal lactate production, and they were not due to muscle hypoxia. PMID- 8482666 TI - Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant. AB - Adult sheep (35 +/- 3 kg) underwent saline lung lavage and 1.5 h of mechanical ventilation to induce acute lung injury. Animals received 100 mg lipid/kg body wt of tracheally instilled surfactant (Inst Surf) or either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) and were killed 3 h later. Inst Surf and Neb Surf groups had significant improvements in oxygenation (P < 0.01) and peak inspiratory pressures (PIP) (P < 0.05) compared with pretreatment values. Improvements in oxygenation and PIP for Inst Surf animals were significantly greater than for Neb Surf animals (P < 0.05). Volumes of maximal pressure of quasi-static pressure-volume curves measured at the time the animals were killed were significantly greater for Inst Surf and Neb Surf animals than for animals given Neb Saline (P < 0.05). Alveolar recovery of exogenous surfactant was 100 times greater for Inst Surf animals (1,732 +/- 70 mg) than for Neb Surf animals (15.3 +/- 2.9 mg) at the time they were killed. Although there were no differences in exogenous surfactant distribution patterns at the lobar level between the two surfactant-treated groups, distribution histograms calculated for 10-g lung pieces revealed the Neb Surf animals had significantly more pieces within 25% of the mean value of 1.0 (42.7 +/- 6.9%) than did Inst Surf animals (20.8 +/- 5.5%) (P < 0.01). Exogenous surfactant therapy improved lung function with significantly different quantities of surfactant deposited in lung tissue for the two delivery methods evaluated. PMID- 8482667 TI - Hemodynamic and respiratory responses to carotid sinus pressure alteration in experimental hypertension. AB - The purpose of this study was to determine whether baroreflex control of respiratory responses is diminished in hypertension. Ten dogs were made chronically hypertensive with use of a bilateral renal wrap technique. Eight sham operated dogs served as normotensive controls. After the development of experimental hypertension, carotid baroreflex control of arterial pressure, heart rate, respiratory frequency, tidal volume, and ventilation was acutely assessed. Under pentobarbital anesthesia and with bilateral vagotomy, the carotid sinuses were isolated and perfused at controlled pressures. Before the carotid sinus region was manipulated, the mean arterial pressure was significantly higher (P < 0.005) in the hypertensive group (146.4 +/- 2.3 mmHg) than in the normotensive group (124.7 +/- 2.6 mmHg). The mean arterial pressures and heart rates measured at every level of carotid sinus pressure were significantly higher in the hypertensive group. Reflex gain of heart rate, but not mean arterial pressure, was significantly reduced in the hypertensive group. Respiratory frequency, tidal volume, and ventilatory responses to changes in carotid sinus pressure were significant and resulted in an approximately 40% reflex change in ventilation. These responses were not diminished in the hypertensive group. We conclude that respiratory baroreflex responses are preserved in experimental hypertension. PMID- 8482668 TI - Site and mechanical conditions for failure of skeletal muscle in experimental strain injuries. AB - Failure in muscle strain injuries has been reported to occur within the muscle belly, at the myotendinous junction, or within muscle near the myotendinous junction. The goal of this investigation was to determine by electron-microscopic examination the site of lesion in whole muscle strained to failure. In addition, site and conditions for failure of stimulated and unstimulated muscle were compared. Frog semitendinosus myotendinous units with intact tendon-bone junctions were strained at physiological strain rates to failure. All failures occurred at or near the proximal myotendinous junction in both stimulated and unstimulated muscle. Stimulated muscle required approximately 30% more force and approximately 110% more energy to reach failure. Electron-microscopic examination of longitudinal sections of small bundles of fibers showed that unstimulated muscle failed within the muscle near the myotendinous junction. Failure occurred in a single transverse plane of each cell within Z disks. Other Z disks near the failure site displayed strains of several hundred percent. Stimulated muscle failed within the lamina lucida at the myotendinous junction in most fibers. No Z disk strain was observed in those fibers. We conclude that the site of failure in muscle strain injuries varies with the state of activation of the cell at the time of injury. Furthermore, the data show that the breaking strength of the Z disk varied with muscle stimulation and indicate the existence of two load bearing systems in parallel within Z disks. PMID- 8482669 TI - Inhaled nitric oxide reverses hypoxic pulmonary vasoconstriction without impairing gas exchange. AB - Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that participates in the regulation of vascular tone. We studied the effects of inhaled NO gas on transient hypoxic pulmonary vasoconstriction and normal lungs in mechanically ventilated sheep. We measured hemodynamics and pulmonary gas exchange. For gas exchange measurements we used conventional blood gas analysis and the multiple inert gas elimination technique to estimate ventilation perfusion heterogeneity. Our hypotheses were 1) inhaled NO reverses hypoxic pulmonary vasoconstriction, 2) the hemodynamic effects of inhaled NO are limited to the pulmonary circulation, and 3) inhaled NO does not impair pulmonary gas exchange and may redistribute blood flow to better ventilated areas of the lungs. Hypoxic pulmonary vasoconstriction was induced by using a hypoxic inspiratory gas mixture. The addition of 20 ppm NO to the hypoxic inspiratory gases returned pulmonary arterial pressure to baseline values. Systemic hemodynamics and gas exchange indexes derived from conventional blood gas analysis remained constant. Gas exchange indexes for ventilation-perfusion ratios and gas dispersions improved. The addition of 20 ppm NO to medical air (21% O2) had no such significant effects on hemodynamics or pulmonary gas exchange. Our findings show that inhaled NO reverses transient hypoxic pulmonary vasoconstriction. The hemodynamic effects of NO are limited to the pulmonary circulation; it does not impair pulmonary gas exchange. Moreover, it redistributes blood flow to better ventilated alveoli. As such, NO has potential in the treatment of lung diseases associated with pulmonary hypertension. PMID- 8482670 TI - Breathing volumes and gas exchange during simulated rapid free ascent from 100 msw. AB - The crew of a disabled submarine can be rescued by means of free ascent through the water to the surface. Pulmonary gas exchange was studied during simulated rapid free ascent in subjects standing immersed to the neck in a pressure chamber. The pressure was rapidly increased to 1.1 MPa [100 meters seawater (msw)] followed by decompression at 0.03 MPa/s (3 msw/s). Effective inspired tidal volume, as estimated by an Ar dilution method, fell gradually to zero during decompression from 20 to 0 msw. Directly determined expired tidal volumes were increased up to two to three times at the time of return to surface pressure compared with pre- and postdecompression volumes. End-tidal PCO2 was increased on compression and fell to a nadir of 3.4 kPa (25 Torr) at the time of return to surface pressure. Thus, intrapulmonary gas expansion caused simultaneous inspiratory hypoventilation and expiratory hyperventilation. If O2-enriched gas is to be used to reduce the risk of decompression sickness, it should be administered early during decompression to alter the intrapulmonary gas composition. The time course of arterial PCO2 changes as reflected by end-tidal values during short-lasting compression/decompression would act to promote inert gas supersaturation in the brain. PMID- 8482671 TI - Cardiopulmonary adaptations to pneumonectomy in dogs. II. VA/Q relationships and microvascular recruitment. AB - Ventilation-perfusion relationships, diffusing capacity for O2, and hemodynamic response were measured at rest and during exercise while five adult dogs breathed air and 15% O2 2 mo (Pnx-A, n = 2) or 12 mo (Pnx-B, n = 3) after right pneumonectomy (removal of 58% of lung tissue). Results were compared with those in five sham-operated controls. The multiple inert gas elimination technique was employed. Maximal O2 uptake was reduced by 50% in Pnx-A and by 15% in Pnx-B. Ventilation-perfusion matching was impaired in Pnx-A but not in Pnx-B. The increase in O2 diffusing capacity during exercise was significantly restricted in Pnx-A but was partially restored in Pnx-B. Mean pulmonary arterial pressure at a given blood flow through the remaining lung was normal in Pnx-A but lower than normal in Pnx-B compared with control values for a single lung. Stroke volume and cardiac output were lower in both Pnx-A and Pnx-B than in controls at a given exercise level. All functional abnormalities were more severe at 2 mo than at 12 mo postpneumonectomy. Gas phase diffusion resistance was present in both Pnx-A and Pnx-B but not in controls. We conclude that physiological compensation postpneumonectomy is progressive. Inability to recruit pulmonary vascular bed with incremental perfusion pressure or flow appears to be the major pathophysiological process that limits early functional capacity after right pneumonectomy. PMID- 8482672 TI - Protein kinase C-mediated pulmonary vasoconstriction in rabbit: role of Ca2+, AA metabolites, and vasodilators. AB - We studied the effects of three chemically distinct protein kinase C activators on pulmonary vascular tone in the buffer-perfused isolated rabbit lung. The three activators, 12-deoxyphorbol 13-isobutyrate (12,13-phorbol), mezerein, and 1 oleoyl-2-acetyl-sn-glycerol, produce concentration-dependent increases in pulmonary arterial pressure, whereas the inactive compound 4 alpha-phorbol 12,13 dibutyrate does not affect pulmonary arterial pressure. Reducing calcium availability with verapamil, a calcium-free buffer, or a chelator of intracellular calcium significantly decreases the response to 12,13-phorbol or mezerein. Pretreatment with phloretin, an inhibitor of protein kinase C, has no affect on the vasoconstriction caused by infusion of a KCl bolus, but it does inhibit in a dose-dependent manner the response to 12,13-phorbol and mezerein. 12,13-Phorbol at a concentration of 2.5 microM, but not of 1 microM, stimulates prostacyclin and thromboxane synthesis by the isolated lung. Because inhibitors of thromboxane synthesis significantly decrease the response, thromboxane likely contributes to the vasoconstriction produced by higher concentrations of 12,13 phorbol and mezerein. Pretreatment with isoproterenol or nitroprusside reduces the increase in pulmonary arterial pressure caused by the protein kinase C activators but does not reverse vasoconstriction, even though subsequent treatment with verapamil does. In summary, activating protein kinase C in the isolated rabbit lung causes long-lasting pulmonary vasoconstriction, reducing calcium availability decreases the response, part of the increase in pulmonary arterial pressure appears secondary to thromboxane generation, and pretreatment with isoproterenol or nitroprusside prevents the vasoconstriction, but posttreatment with these vasodilators is ineffective. PMID- 8482673 TI - Relationship of pulmonary arterial pressure and airflow obstruction to emphysema. AB - Guinea pigs were exposed to cigarette smoke for 6 mo, after which lung and cardiac function and lung morphology were examined. The smoke-exposed animals were divided into two groups on the basis of final pulmonary arterial pressure. We found that the smoke-exposed animals with increased pulmonary arterial pressure had a moderate degree of airflow obstruction compared with the normotensive smoke group, which showed only mild airflow obstruction, and with the control group. Both smoke groups had similar degrees of emphysema. Although both smoke groups had an increased percentage of muscularized small arterioles, only the group with increased pulmonary arterial pressure had an altered flow pressure response to dobutamine. We conclude that although cigarette smoke appears to induce changes in the vascular structure and to produce emphysematous lung destruction, the increased pulmonary arterial pressure in guinea pigs chronically exposed to smoke is not directly related to either of these findings. Instead, it appears that there is a dynamic alteration of both the airways, producing airflow obstruction, and the vasculature, producing increased pulmonary arterial pressure. PMID- 8482674 TI - Effect of inspiratory muscle unloading on arousal responses to CO2 and hypoxia in sleeping dogs. AB - Chemical respiratory stimuli can induce arousal from sleep, but the specific mechanisms involved have not been established. Therefore, we tested the hypothesis that mechanoreceptor stimuli arising in the ventilatory apparatus have a role in the arousal responses to progressive hypercapnia and hypoxia by comparing arousal responses during spontaneous ventilation with those obtained when the inspiratory muscles were unloaded by mechanical ventilatory assistance. Studies were performed in three trained dogs in which the adequacy of inspiratory muscle unloading was verified by diaphragmatic electromyographic (EMG) recordings. In rapid-eye-movement (REM) sleep the arousal threshold during progressive hypercapnia increased from 68.4 +/- 0.5 (SE) mmHg during spontaneous runs to 72.3 +/- 0.8 mmHg during mechanically assisted runs (P < 0.01). In contrast there were no changes in arousal responses to hypercapnia during non-REM (NREM) sleep or to hypoxia in either NREM or REM sleep. However, during the assisted hypoxic runs, EMG activity of the transversus abdominis muscle was increased compared with the unassisted runs; therefore, the effects on arousal threshold of unloading the inspiratory muscles may have been offset by increased loading of the expiratory muscles. The findings indicate that even in the absence of added mechanical loads, mechanoreceptor stimuli probably arising in the respiratory muscles contribute to the arousal response to hypercapnia during REM sleep. PMID- 8482675 TI - Inhaled FMLP increases microvascular permeability in the rabbit trachea. AB - This study was designed to determine the effect of inhaled N-formyl-methionyl leucyl-phenylalanine (FMLP) on microvascular permeability in the rabbit trachea and to determine if the effect could be modified by cholinergic antagonism, neutral endopeptidase (NEP) inhibition, opioid receptor antagonism, or an opioid agonist. New Zealand White rabbits were anesthetized and pretreated intravenously with one of the following: saline, dimethyl sulfoxide (DMSO) (both controls), thiorphan, phosphoramidon (both NEP inhibitors), thiorphan and naloxone, morphine, or atropine. All rabbits were then given intravenous Evans blue before inhalation of nebulized DMSO (control) or FMLP. Extravascular tracheal Evans blue concentration was subsequently determined spectrophotometrically. FMLP caused a highly significant increase in microvascular permeability (92.6 +/- 7.1 micrograms/g of trachea, control 20.4' +/- 3.4). The effect of FMLP was significantly modified by cholinergic blockade (61.1 +/- 6.9) and by NEP inhibition (thiorphan 38.8 +/- 5.6, phosphoramidon 52.6 +/- 4.2). This effect of NEP inhibition could be reversed by concurrent treatment with the opioid receptor antagonist naloxone (95.9 +/- 34.6). Morphine had no significant effect. We concluded that FMLP increases microvascular permeability, which may in part explain the effect of FMLP on airway resistance in the rabbit. Inhibiting NEP decreases the response possibly through an effect on endogenous opioids. The response appears to be partially vagally mediated. PMID- 8482676 TI - Muscle metabolism during lactate infusion in human phosphofructokinase deficiency. AB - We studied the effect of intravenous infusion of sodium lactate (La) on muscle high-energy phosphate metabolism, pH, and venous effluent [NH3] in three patients with muscle phosphofructokinase (PFK) deficiency and three healthy subjects during maximal-effort rhythmic handgrip exercise (5 s of contraction alternated with 5 s of rest) performed for 3 min. Healthy subjects were matched to PFK deficient patients for gender and maximal handgrip strength. Force production was recorded and during lactate infusion was matched to that without lactate. 31P magnetic resonance spectroscopy was used to measure intracellular phosphocreatine (PCr), orthophosphate (Pi), ATP, and pH in the flexor digitorum profundus of the exercising forearm. La infusion had no effect on healthy subjects or patients during rest. In healthy subjects, La infusion had no effect on depletion of PCr; accumulation of Pi, ADP, or venous effluent NH3; or decline in pH in exercising muscle. In contrast, during exercise in PFK-deficient patients, [PCr] was higher (17.9 +/- 1.9 vs. 13.1 +/- 1.4 mmol/kg) and [phosphomonoester] (11.4 +/- 1.3 vs. 6.5 +/- 1.4 mmol/kg), [Pi] (9.2 +/- 1.8 vs. 5.0 +/- 0.7 mmol/kg), [ADP] (60.4 +/- 7.0 vs. 37.9 +/- 9.9 mumol/kg), and venous effluent [NH3] (335 +/- 136 vs. 176 +/ 61 mM) were lower (P < 0.05) during La infusion than in control conditions. The effects of La infusion on intracellular [PCr], [Pi], [phosphomonoester], [ADP], and [NH3] in PFK-deficient patients are consistent with the hypothesis that exogenous La augments the rate of oxidative phosphorylation in active muscle by bypassing the enzymatic block at PFK. PMID- 8482677 TI - Role of tendon properties on the dynamic performance of different isometric muscles. AB - The effect of the tendon's viscoelastic stiffness on the dynamic performance of muscles with different architecture was determined using the cat's medial gastrocnemius and extensor digitorum longus. Dynamic response models were derived under sinusoidal contraction-relaxation in the range of 0.4-6.0 Hz and between 20 and 80% of the muscles' maximal isometric tension, manipulated by orderly recruitment-derecruitment of motor units together with firing rate increase decrease. It was shown that, for isometric contractions at the muscle's optimum length, the dynamic response of the muscles was not significantly different before and after dissection of the tendon. Therefore the conclusion that under these conditions the tendon acts like a stiff force transmitter without significantly modifying the muscle's performance was confirmed and extended to muscles with different architecture. PMID- 8482678 TI - Quantifying the effect of intravascular perfluorocarbon on xenon elimination from canine muscle. AB - Intravenous infusions of perfluorocarbon (PFC) may improve decompression sickness outcome in animals by accelerating inert gas elimination from tissue, but any such effect has not been quantified experimentally. In this study we used an animal model of tissue Xe kinetics to test this hypothesis and to quantify the effect of PFC. Eight dogs were ventilated with dilute 133Xe in air for 4 h of Xe uptake. Four dogs were then given an infusion (20 ml/kg iv) of a 40% (vol/vol) perfluorodecalin-glycerol emulsion, and four control dogs were given only isotonic glycerol. All were then switched to open-circuit air breathing for 4 h of Xe elimination. During this time Xe radioactivity-time curves were recorded from two intact hind leg muscles, and the Xe mean residence times during elimination were estimated using an analysis by moments and compared by group. Tissue blood flows were measured using microspheres once during Xe uptake and twice during Xe elimination, and cardiac outputs were measured by thermodilution at 30-min intervals. In the PFC group the measured circulating PFC fraction increased the calculated Xe solubility by an average factor of 1.77 and so was expected to increase the Xe elimination rate by 77%. The observed Xe mean residence times on elimination for the PFC group averaged 33.5 min [95% confidence interval (CI) 19.5-47.6] compared with the glycerol control average of 70.1 min (95% CI 56.1-84.2), representing an increase in the rate of Xe elimination by a factor of 2.09 or 109%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482679 TI - Physical and cytochemical properties of neutrophils activated in situ in the lung during ZAP infusion in sheep. AB - Increased retention of activated neutrophils in the lungs contributes to endothelial cell injury. However, characterization of the morphological changes that occur in neutrophils during activation in the pulmonary microcirculation has not been fully determined in vivo. Therefore, the present study was designed to determine structural and cytochemical properties of neutrophils in situ in pulmonary arterioles and alveolar capillaries during the infusion of zymosan activated plasma (ZAP) or plasma (control) in anesthetized sheep. Quantitative morphological methods showed that ZAP infusion caused significant retention of neutrophils in alveolar capillaries [2.19 +/- 0.40 (SD) x 10(8) neutrophils/ml of capillary blood volume] and pulmonary arterioles (1.02 +/- 0.46 x 10(8) neutrophils/ml of arterial blood volume) compared with plasma infusion (1.03 +/- 0.15 and 0.30 +/- 0.10 x 10(8) neutrophils/ml, respectively; P < 0.05). Harmonic mean diameter of ZAP-activated neutrophils in situ (7.19 +/- 0.44 microns) was significantly greater than the diameter of neutrophils in plasma-treated sheep (6.29 +/- 0.17 microns; P < 0.05). Neutrophil cross-sectional area (54 +/- 3 microns2) and volume (248 +/- 27 microns3) in situ in alveolar capillaries were also significantly greater in ZAP-treated sheep than in control sheep (41 +/- 4 microns2 and 184 +/- 9 microns3, respectively; P < 0.05). Similarly, microvascular neutrophils in ZAP-treated sheep were vacuolated and elongated, filamentous actin was redistributed peripherally, and the cells were degranulated. We conclude that during ZAP infusion, neutrophils become enlarged and degranulated in pulmonary microvessels, especially in alveolar capillaries. The structural and cytochemical changes that occur are consistent with the hypothesis that neutrophil activation is accompanied by alterations in neutrophil physical properties, alterations that may facilitate retention and contribute to endothelial cell injury. PMID- 8482680 TI - Factors influencing measurement of protein reflection coefficient by filtered volume technique. AB - In isolated perfused organs, the protein reflection coefficient (sigma) can be estimated by comparing increases in hematocrit (Hct) and protein concentration (CP) during transvascular fluid filtration. In this study, we developed an equation for sigma to examine the potential influences of perfusate leak, evaporation, and hemolysis-induced changes in red blood cell volume and perfusate water. We also performed experiments in isolated ferret lungs to quantitate the magnitude of these potential sources of error and the effects of free hemoglobin on measurements of CP. These studies demonstrated that 1) perfusate leak does not cause an error because its effects on changes in Hct and CP counteract each other; 2) evaporation causes an overestimation of sigma, but in our experiments this effect was small; 3) hemolysis-induced changes in red blood cell and perfusate water volumes may cause an over- or underestimation of sigma, but these effects are small; 4) overestimations of CP due to increasing free perfusate hemoglobin concentration can cause substantial overestimations of sigma; and 5) values of sigma calculated from previous equations and from our equation were virtually identical, suggesting that the assumptions necessary for the previous equations were not significant sources of error. In agreement with previous workers, we conclude that the most important potential source of error is hemolysis-induced increases in free perfusate hemoglobin. PMID- 8482681 TI - Skeletal muscle calcium-activated neutral protease (calpain) with exercise. AB - The purpose of this study was to investigate whether exercise could induce calpain activation by altering the Ca2+ required for half-maximal activity (pCa50) and/or susceptibility of digestible muscle protein substrates. Rats (225 g) were assigned to control, exercise (25 m/min, 0% grade), and 24-h recovery groups. Exercise resulted in a generalized 48 +/- 18% loss of muscle glycogen and a twofold increase in plasma creatine kinase levels (P < or = 0.05). Exercise increased total caseinolysis of diethylaminoethyl Sepharose-prepared low (u) and high (m) Ca2+ calpain isoforms by 22 and 30%, respectively (P < or = 0.05). The pCa50 of u- and m-calpain with exercise increased from 5.98 +/- 0.12 to 6.20 +/- 0.15 (P > or = 0.05) and from 3.63 +/- 0.10 to 3.90 +/- 0.16 (P > or = 0.05), respectively. In vitro, calpain-mediated degradation/disappearance rates (i.e., percentage of protein degraded in 10 min) for control tropomyosin and alpha actinin were 69 and 30% compared with 92 and 61% after exercise (P < or = 0.05). The results of this study confirm that level running increases total nonlysosomal Ca2+ specific protease activity, which may promote exercise-induced muscle damage or fatigue. PMID- 8482682 TI - Tissue resistance and the contractile state of lung parenchyma. AB - When challenged with a contractile agonist in increasing graded concentrations, lung parenchymal tissue assumes a sequence of mechanical states. That sequence is mapped here. Isolated lung parenchymal strips from male Hartley guinea pigs were mounted in a bath containing Krebs solution at 37 degrees C, aerated with 95% O2 5% CO2. One end was attached to a force transducer and the other to a servo controlled lever arm. After stress adaptation, sinusoidal length oscillations (1% strain at 0.31 Hz) yielded force-length loops from which we computed induced changes in active tension (F), tissue stiffness (E), and hysteresivity (eta) (J. J. Fredberg and D. Stamenovic. J. Appl. Physiol. 67:2408-2419, 1989). Changes of tissue resistance (R) were, by definition, governed by those of eta and E. Histamine (10(-6) -10(-3) M), prostaglandin D2 (10(-5) -10(-4) M), and prostaglandin F2 alpha (10(-5) -10(-4) M) caused dose-related increases of F, eta, and E. Plotting induced changes of E vs. those of F revealed a unique relationship that was identical for these as well as a wider panel of contractile agonists; changes of E and F were closely associated. However, plotting induced changes of E vs. those of eta revealed relationships that differed distinctly between agonists; changes of eta were dissociated from those of F and E. This latter observation demonstrated the existence of distinct mechanical states that differed according to the specific agonist by which the tissue was stimulated. In producing agonist-induced changes in R, changes of E were of equal or greater importance compared with those of eta. We conclude that guinea pig lung parenchyma, viewed as an integrated physiological tissue system, exhibits different kinds as well as varying intensities of mechanical response according to the specific agonist present in the cellular microenvironment. These differences in contractile state reveal themselves principally in the hysteretic nature of the tissue. PMID- 8482683 TI - Abdominal compliance, parasternal activation, and chest wall motion. AB - We measured abdominal compliance (Cab) and rib cage displacement (delta Vrc) relative to abdominal displacement (delta Vab) during relaxation and tidal breathing in upright (U) and supine (S) postures in five normal subjects. In S, an abdominal binder was used to decrease Cab in two to five increments. We also measured the electrical activity of the parasternal muscle (EMGps) with the use of fine-wire intramuscular electrodes during CO2 rebreathing in U and in supine unbound (SU) and supine bound (SB) postures. During maximum binding (SB2), Cab decreased to 39 +/- 7% of the SU value (P = 0.01), matching Cab in U (P = 0.16). In the SB condition, the ratio of tidal delta Vrc/delta Vab to relaxation delta Vrc/delta Vab increased as Cab decreased, matching the data in U. For the group, this ratio decreased during SU to 47 +/- 10% (P = 0.02) but increased during SB2 to 86 +/- 7% (P = 0.18) of the value in U. During CO2 rebreathing, EMGps increased linearly with tidal volume (r > 0.727, P < 0.01). However, at any given tidal volume, the SU and SB2 EMGps were not significantly different (P = 0.12), and both were less than that in U (P < 0.02). The results suggest that the differences in chest wall motion between U and S may be due to the difference in Cab and not to different patterns of respiratory muscle recruitment. The mechanism may relate to changes in mechanical coupling between the diaphragm and the rib cage. PMID- 8482684 TI - Costal and crural diaphragm function during CO2 rebreathing in awake dogs. AB - If costal and crural diaphragm segments can perform as separate muscles, then CO2 stimulated ventilation may elicit differential segmental function. We studied diaphragm segmental length, shortening, and electromyogram (EMG) activity in 10 awake dogs chronically implanted with sonomicrometer transducers and EMG electrodes. During CO2 rebreathing, segmental shortening and EMG activity per whole tidal breath progressively increased, but segmental responses could not be differentiated at any level of CO2. With increasing CO2, resting end-expiratory length of both diaphragm segments increased. During the complete intrabreath inspiratory-expiratory cycle, costal and crural diaphragm revealed distinctive segmental function. At rest, crural shortening exceeded costal shortening in earliest inspiration, costal and especially crural shortening persisted into early expiration, and EMG activity of the crural segment was greater than that of the costal segment in earliest inspiration and showed more end-inspiratory/early expiratory [post-inspiratory inspiratory activity (PIIA)] activity. During CO2 stimulated breathing, neither segment shortened during the inspiratory flow of earliest inspiration. During CO2 rebreathing, shortening of the crural segment exceeded that of the costal segment during early inspiration and outlasted costal shortening during expiration; for both segments, shortening persisted after termination of inspiratory airflow. With increased CO2, EMG activity of the crural segment preceded that of the costal segment in earliest inspiration and was dominant into expiration, whereas costal EMG activity terminated abruptly with inspiratory flow. Thus, costal EMG PIIA was not evident during hypercapnia, whereas crural EMG PIIA was significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482685 TI - Effect of nebulized lidocaine on ventilatory response to CO2 in healthy subjects. AB - Partial vagal blockade produced by inhalation of a local anesthetic aerosol has enhanced CO2 responsiveness in some studies but not in others. The effect of inhaled local anesthetic may depend on the amount of drug depositing in the central airways, i.e., the degree of airway anesthesia. We examined the ventilatory response to CO2 rebreathing in 11 healthy subjects before and after inhalation of 4% lidocaine and a normal saline control solution. Lidocaine and control solutions were aerosolized via two different nebulizers: one produced particles with a mass median aerodynamic diameter of 5.28 microns, and the other produced particles with a mass median aerodynamic diameter of 1.76 microns. The ventilatory response to CO2 was not affected by the control solution. In contrast, the ventilatory response to CO2 was significantly increased after aerosolized lidocaine when administered via the moderate-particle-size nebulizer (2.13 +/- 0.66 vs. 1.83 +/- 0.54 l.min-1.Torr-1 during control, P = 0.01) but not via the small-particle-size nebulizer (1.96 +/- 0.82 vs. 1.94 +/- 0.84 l.min 1.Torr-1 during control, P = NS). The increase in ventilation was achieved predominantly by an increase in frequency (P = 0.01) while tidal volume was unchanged. In conclusion, airway receptors accessible to inhaled local anesthetic play a role in the control of breathing during CO2 rebreathing. Previous negative studies may be due to differences in nebulizer technique, affecting the amount of drug depositing within the central airways. PMID- 8482686 TI - Polyethylene glycol-conjugated superoxide dismutase protects rats against oxygen toxicity. AB - Superoxide dismutase (SOD) has an important role in the protection against O2 toxicity. Conjugation of Cu,Zn-SOD to polyethylene glycol (PEG-SOD) prolongs its plasma half-life and facilitates its cellular uptake. However, prior studies have shown that intravenous injection of PEG-SOD does not protect animals against O2 toxicity. In this study, we demonstrated that tracheal insufflation of PEG-SOD resulted in a dose-dependent protection against O2 toxicity. Nine of 15 rats (60%) insufflated with 25,000 U PEG-SOD survived continuous 100% O2 exposure for more than 7 days compared with control rats (n = 45), all of which died within 3 days of O2 exposure (P < 0.025). In contrast, insufflation of 25,000 U SOD, 9.7 mg methoxy-PEG (equivalent to the amount of methoxy-PEG present in 25,000 U PEG SOD), or a combination of SOD and methoxy-PEG had no protective effect. Furthermore, intravenous or intraperitoneal injection of PEG-SOD did not afford significant protection. Protection against O2 toxicity by PEG-SOD insufflation was associated with attenuated O2-induced pulmonary injury as evidenced by a reduced volume of pleural effusion. Insufflation of PEG-SOD markedly increased pulmonary SOD activity (to 300 and 370% of controls at 24 and 50 h, respectively) without affecting pulmonary catalase activity. We conclude that insufflation of PEG-SOD protects rats against O2 toxicity, possibly by enhancing pulmonary SOD activity. PMID- 8482687 TI - Inhibition of leukocyte adherence and aggregation for treatment of severe cold injury in rabbits. AB - We tested the hypothesis that blocking neutrophil adherence and/or aggregation reduces tissue injury that results when tissue is frozen and rewarmed. The left hindlimbs of three groups of New Zealand White rabbits were immersed in a -15 degrees C salt water bath for 30 min to freeze the foot. The foot was rewarmed in a 39 degrees C water bath. In two groups, adherence and aggregation were blocked with monoclonal antibody (MAb) 60.3, and the third group was treated with saline. Two of the groups were treated at the time of rewarming with either saline or MAb 60.3, and the third group received MAb 60.3 at the conclusion of rewarming. Tissue edema and tissue loss were significantly less in the two groups receiving MAb 60.3 than in the control group. Rabbits treated at the time of rewarming had less edema and tissue loss than those treated at the completion of rewarming. These studies indicate that a substantial component of severe cold injury is neutrophil mediated and occurs after rewarming. PMID- 8482688 TI - Epithelial modulation of preterm airway smooth muscle contraction. AB - To determine if epithelium from immature airways can modulate the responsiveness of smooth muscle, we studied paired trachealis muscle strips from preterm sheep. The epithelium was removed from one strip and left undisturbed in the other. Concentration-effect (CE) curves to acetylcholine (ACh), KCl, and isoproterenol were obtained. To evaluate maturational effects, responses to ACh and isoproterenol were studied in trachealis strips from adult airways. Maximal stress (Po) to ACh increased after epithelium removal in preterm (P < 0.05) but not adult strips. Epithelium removal caused a leftward shift of the ACh CE curves in both preterm and adult strips (P < 0.001) and a decrease in the dose required to achieve a one-half maximal response (ED50) in both preterm (P < 0.005) and adult strips (P < 0.05). The magnitude of the change in Po as well as in the ED50 for ACh between preterms and adults was similar. Epithelium removal did not alter either the Po or the CE curves of preterm strips stimulated by KCl. Response to isoproterenol in precontracted strips was enhanced in the presence of an intact epithelium in both groups (P < 0.05). These data demonstrate that preterm airway epithelium is able to modulate the responsiveness of smooth muscle. Additionally, the magnitude of the effect is unchanged with maturation. We speculate that damage of airway epithelium from mechanical ventilation may contribute to the increased incidence of airway hyperreactivity observed in preterm infants. PMID- 8482689 TI - Model-free numerical deconvolution of recirculating indicator concentration curves. AB - This paper investigates two model-free methods for numerical deconvolution of recirculating indicator concentration curves. The two methods, damped least squares and discrete orthogonal polynomial deconvolution, are applied to simulated data to verify the reliability of the algorithms. Both deconvolution methods provide damping that results in estimated transport functions that are smooth and reasonable estimates of the actual simulated transport function. On convolution with the simulated input curve, the estimated transport functions provide good fits to the simulated output curve. In addition, methods for identifying an optimal solution and for truncating the artifactually long oscillatory tails of the estimated transport functions are proposed, which appear to allow for reasonably accurate estimation of the mean transit times and variances of the transport functions as well. When either method was applied to indicator dilution data obtained from the pulmonary artery and left atrium, it was computationally stable while producing transport functions that when convolved with the input concentration curves provided good fits to the output concentration curves. The combined simulation and experimental results suggest that the proposed methods should be useful for estimating circulation transport functions from indicator dilution data. PMID- 8482690 TI - Multielectrode mapping of slow-wave activity in the isolated rabbit duodenum. AB - The technique of multiple simultaneous recordings from a large number of extracellular electrodes (> 100) is currently used in the study of normal and abnormal electrical conduction in the heart and the genesis of cardiac arrhythmias. To investigate whether such a system could also be applied in gastrointestinal electrophysiology, several studies were performed with this technique on segments of isolated rabbit duodenum. A multiple-electrode assembly consisting of 240 silver wires was positioned on the serosal surface of the duodenum, and the recorded signals were, after suitable processing, stored. Thereafter, analysis of all simultaneously recorded slow waves during a selected period of time was performed to reconstruct the pattern of conduction in the duodenum. The first results show that there is a considerable variation in conduction pattern, which is determined by the site of the natural pacemaker. Several experiments were performed to rule out possible deleterious effects of positioning the multiple-electrode assembly on the duodenum. Furthermore, prolonged periods of recording did not influence propagation speed and pattern provided that the positioning of the multiple electrode assembly was performed with care. Entrainment of the natural pacemaker was possible by applying electrical stimuli through 2 of the 240 extracellular electrodes during simultaneous recordings. In conclusion, multisite extracellular mapping of gastrointestinal smooth muscle is possible and can be used to study origin and spread of slow-wave activity. PMID- 8482691 TI - Measurement of microhemodynamics in the ventilated rabbit lung by intravital fluorescence microscopy. AB - Pulmonary microhemodynamic parameters were directly measured along with systemic pressures and cardiac output in the ventilated rabbit lung. Subpleural arterioles and venules ranging from 10 to 35 microns luminal diameter were investigated under zone 2 conditions, i.e., during inspiratory plateau at an airway pressure of 8 mmHg. Mean arteriolar and venular diameters (24.6 +/- 3.3 and 21.9 +/- 3.6 microns, respectively), mean red blood cell (RBC) fluxes (1,549 +/- 501 and 1,257 +/- 600 cells/s), and mean RBC velocities (0.79 +/- 0.21 and 0.82 +/- 0.21 mm/s) were measured using a fluorescence video-microscopic technique. Calculated microhematocrit (Hct mu) was below systemic values (Hctsys) (Hct mu/Hctsys: arterioles, 0.75 +/- 0.12; venules, 0.67 +/- 0.08). The mean capillary transit time of RBC was 0.47 +/- 0.16 s over a mean arteriovenous distance of 173 +/- 70 m. Significant correlations were demonstrated between microhemodynamic parameters. A correlation among cardiac output, pulmonary arterial pressure, and RBC velocity demonstrates the connection between macro- and microhemodynamics in the rabbit lung. In conclusion, the present model is the first one enabling the measurements of the principal circulatory determinants for gas exchange, i.e., microvascular blood flow, Hct mu, and capillary transit time of RBCs in the ventilated rabbit lung under simultaneous macrocirculatory control. PMID- 8482692 TI - Effects of low-dose dopamine on gut ischemia in a porcine model of hemorrhagic shock. PMID- 8482693 TI - Exercise and resistance to infection. AB - The influence of exercise on resistance to infection has been debated for decades. Part of this controversy is due to the complex interactions between pathogens and host defense mechanisms as well as to the mutable nature of exercise. Psychological influences and normal temporal variations in immune mechanisms have also complicated the issue. An understanding of how each of these factors affects host defense should help in the design of new experimental approaches to the problem as well as in the interpretation of previously published results. PMID- 8482694 TI - O2-induced changes in lung and storage pool thiols in mice: effect of superoxide dismutase. AB - Because glutathione (GSH) is an important antioxidant, we hypothesized that changes in lung and systemic availability of GSH and its precursor amino acid, cysteine, are induced by exposure to hyperoxia and that these changes could be modulated by toxic O2 metabolites. In organs and plasma of mice exposed to hyperoxia, we measured GSH and sulfur-containing amino acids (SAAs), the latter by capillary gas chromatography-mass spectrometry. In relatively O2-resistant Swiss-Webster mice, lung GSH increased during O2 exposure, whereas liver GSH (the major storage pool of cysteine) and liver and plasma cysteine all decreased. Pair feeding studies suggested that nutritional deprivation alone did not cause the decrease in plasma cysteine. In lung, SAAs were not decreased by O2 exposure. In fact, cystathionine increased sixfold, and gamma-cystathionase was not inhibited. These findings suggest that hyperoxia increases transsulfuration pathway activity and that cystathionase rate limits this process in lung. In comparative studies, lung GSH increased in O2-resistant high-CuZn superoxide dismutase (SOD) transgenic mice but not in genetically similar, nontransgenic controls (CBYB/6 x B6D/2) during hyperoxic exposure. In addition, liver GSH and plasma cysteine decreased in nontransgenic control but not in high-SOD mice, whereas lung cystathionine increased similarly in both groups. Thus, superoxide or its secondary products can modulate, at least in part, the changes in cysteine and GSH. Nonetheless, regardless of strain or SOD status, hyperoxic exposure consistently caused thiol and SAA changes, including increased lung cystathionine and oxidized GSH, demonstrating a strong association between these dynamic changes and oxidant stress. PMID- 8482695 TI - Withdrawal of placental prostaglandins permits thermogenic responses in fetal sheep brown adipose tissue. AB - Significant nonshivering thermogenesis cannot be demonstrated in fetal sheep cooled in utero but can be induced by supplemental oxygenation and umbilical cord occlusion, which suggests the presence of inhibitor(s) of placental origin. To test the hypothesis that an ecosanoid could be such an inhibitor, we studied eight fetal sheep at 136-141 days gestation. Thermistors were placed in the fetal esophagus, a cooling tube was placed around the trunk, a tracheal cannula and carotid catheters were inserted, and a snare was placed loosely around the umbilical cord. After indomethacin infusion for 18 h, the fetuses were cooled by 2.13 +/- 0.13 degrees C by circulating cold water through the coil. Within 60 min plasma free fatty acid levels rose threefold to 245 +/- 82 mu eq/l (P < 0.01) and glycerol levels rose to 197 +/- 17 mumol/l (P < 0.01). Ventilation caused a further rise in thermogenic indexes, and fetal oxygen consumption rose to 19.9 +/ 1.2 ml.kg-1.min-1. In four fetuses we ceased cooling, which caused thermogenic indexes to fall and oxygen consumption to fall to 6.9 +/- 1.1 ml.kg-1.min-1. We continued to cool three fetuses and infused prostaglandin E2 into the fetuses for 60 min; thermogenic indexes and oxygen consumption fell rapidly on infusion and rose rapidly when infusion ceased. We suggest that placental prostaglandins inhibit brown adipose tissue thermogenesis before birth and that withdrawal after placental separation is one factor in the initiation of nonshivering thermogenesis at birth. PMID- 8482696 TI - Utility of predicting group membership and the role of spatial visualization in becoming an engineer, physical scientist, or artist. AB - This article has two themes: First, we explicate how the prediction of group membership can augment test validation designs restricted to prediction of individual differences in criterion performance. Second, we illustrate the utility of this methodology by documenting the importance of spatial visualization for becoming an engineer, physical scientist, or artist. This involved various longitudinal analyses on a sample of 400,000 high school students tracked after 11 years following their high school graduation. The predictive validities of Spatial-Math and Verbal-Math ability composites were established by successfully differentiating a variety of educational and occupational groups. One implication of our findings is that physical science and engineering disciplines appear to be losing many talented persons by restricting assessment to conventional mathematical and verbal abilities, such as those of the Scholastic Aptitude Test (SAT) and the Graduate Record Examination (GRE). PMID- 8482697 TI - Surviving self-employment: a personal case history. AB - In the popular perception of what determines one's success as a free-lance illustrator, issues other than natural talent or artistic ability are seldom emphasized. In addition to a firm philosophical foundation and a good work ethic, the organization and management of practical concerns play significant roles in the successful operation of any free-lance business. Presented as a personal history, this article discusses some of the most important, yet most neglected, issues that are essential to the economic security and survival of anyone considering a career as a free-lance illustrator. PMID- 8482698 TI - Computer utilization trends in biomedical illustration. AB - A national study was designed to determine computer utilization trends in biomedical art and illustration in North America. In the fall of 1991, 453 surveys were mailed to the Association of Medical Illustrators and the Association of Biomedical Communications Directors; 112 (25%) completed survey forms were returned. The survey compares similarities and differences between the groups with regard to the impact (e.g., staffing, time, cost, and quality control) of computer technology (e.g., hardware, software) on biomedical artwork in the health sciences. PMID- 8482699 TI - Imaging technologies in cardiovascular interventions. AB - New and exciting vascular imaging technologies are assuming increasingly important roles in the management of vascular disease. Non-invasive modalities such as computerized tomography, magnetic resonance imaging and duplex ultrasound supplement the information obtained by invasive techniques including angiography, angioscopy and intraluminal ultrasound. This paper outlines the modern and developing vascular imaging techniques that are rapidly becoming integral components of therapeutic devices as well as advanced diagnostic systems. PMID- 8482700 TI - Aortic dissection: anatomic types and surgical approaches. AB - Our classification system of acute dissection of the aorta is based on the site of the main intimal tear: Type A: on the ascending aorta; type B: on the transverse aortic arch; type C: on the descending aorta. The extension of the dissecting process is classified as "antegrade" or "retrograde". Acute dissection involving the ascending aorta is an absolute surgical urgency. Any delay in referring the patient to a proper surgical institution or to the operating room increases the risk of death. Fifty per cent of patients, indeed, either untreated or medically supported, die within 48 hours after the onset of symptoms. Surgical therapy is mainly aimed at preventing the patient from dying from intrapericardial rupture of the aorta or from acute massive aortic regurgitation. In type A, it is necessary to replace the ascending aorta with a bloodtight Dacron prosthesis after resecting the entry site, if possible. Downstream, joining the two dissected cylinders by two running sutures and the aid of GRF glue, seals the false lumen. Upstream, the reconstruction of the aortic root and the resuspension of the aortic valve, also by means of running sutures and GRF glue, suppress the aortic valve insufficiency in 90% patients. However, in case of pre-existing annulo-aortic ectasia, the ascending aorta must be replaced by a composite tube according to the Bentail technique. The use of GRF glue since the beginning of 1977, has dramatically improved the immediate and long-term results, accounting for a hospital mortality rate of 10%, in patients less than 65 years old. In type B, resecting the entry site requires that the transverse arch be partially or totally replaced. It is, therefore, mandatory to protect the Central Nervous System. In our experience this is best achieved by perfusing the carotid arteries with cold blood (6 degrees C) during circulatory arrest at moderate core hypothermia (28 degrees C). With this technique of "Cerebroplegia", the hospital mortality rate has been lowered to 28%, higher, though, than in patients undergoing isolated replacement of the ascending aorta. In type C, only the dissections demonstrating symptoms of major complications (rupture or deleterious ischemia) require urgent surgical treatment. In the remaining cases, medical treatment, based on permanent and accurate control of the patient's blood pressure, lead to a good long-term survival rate. Close survey at regular intervals, by means of CT scan or MNR is mandatory to detect any aneurysmal evolution, which may require surgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8482701 TI - Noninvasive tests in venous insufficiency. AB - Chronic venous insufficiency (CVI) is the result of outflow obstruction, reflux or a combination of both. Noninvasive tests detect an quantify obstruction and reflux if present and define the anatomic localisation of the abnormality. In evaluating CVI noninvasive tests combine physiologic and imaging techniques. These tests are widely available, simple, quick and cost-effective and therefore they are the methods of choice for initial objective evaluation. Different tests provide answers to different questions. The optimum clinically useful information can be now obtained using only three instruments: pocket Doppler, duplex or color duplex scanner and air plethysmography. The value of ambulatory venous pressure, photoplethysmography and light reflection reography, air plethysmography, duplex and color duplex scanning to assess reflux and the value of tests to assess out flow obstruction are presented. Pooled data collected from large studies are also presented for reference. Qualitative and quantitative assessment of CVI are useful both for clinical assessment and to evaluate the effect of treatments. PMID- 8482702 TI - Reconstruction of major arteries of extremities after war injuries. AB - This paper reports on the experience regarding the reconstruction of arterial injuries gained at the Department of Surgery, Osijek General Hospital during the first year of war against Croatia. In the period between May 1991 and May 1992, 57 wounded with 60 injuries of the major arteries of the extremities were admitted to the hospital, all of them directly from the battlefield or from the streets of Osijek. As there is no consensus on the application of autologous vein graft or allograft in arterial injury reconstruction, our choice of surgical management and early results are reviewed. In the surgical repair of 60 injured major arteries of the extremities, 17 allografts and 19 autologous vein grafts were used. In conclusion, our results indicate that the use of allografts for arterial injury reconstruction may be useful in a highly contaminated area of war wound. PMID- 8482703 TI - Rupture of abdominal aortic aneurysms into the major abdominal veins. AB - Over the period January 1965-July 1992 26 spontaneous fistulas between an abdominal aortic aneurysm (AAA) and the major abdominal veins were observed and surgically treated. Twenty-two were aorto-caval, one iliaco-iliac and 3 aorto iliac; since clinical features, pathophysiology, principles of surgical treatment and postoperative care are similar, both the conditions are considered as a single disease (aorto-caval fistula: ACF). The incidence among 373 ruptured AAA operated in emergency conditions in the same period was 6.97%, with an operative mortality rate of 34.61% compared to an overall mortality for ruptured AAA of 34.85%. All subjects were males with a mean age of 67.3 years. Twelve subjects showed shock at admission (46.1%): the mortality rate in this subgroup was 50% compared to 21.4% among the non-shocked patients. Pain was always present, oedema of one or both of the lower limbs in 9 cases (34.6%) and abdominal bruit or murmur and thrill in 16 (61.5%). One patient died at laparotomy for irreversible cardiac arrest; the 25 completed procedures consisted of endoaneurysmal repair of the fistula under venous bleeding control by digital compression and prosthetic replacement of the abdominal aorta (7 straight and 18 bifurcated grafts). Intraoperative mean blood losses exceeded 4,000 ml, but autotransfusion, available only in 12 procedures, allowed significant sparing of heterologous blood units. The mortality rate was not clearly improved by autotransfusion, but among these 12 patients shock was present in 7 instances (58.3%), compared to 5 out of 14 subjects (35.7%) operated on before autotransfusion devices were available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482704 TI - Cardiac myxomas: surgical treatment, long-term results and recurrence. AB - Long-term results of the surgical treatment of cardiac myxomas are not completely understood due to its recurrence. We review our experience in 27 operated cases with a follow-up to 22 years (mean 6.5 years), in order to throw light on results and review the problem of recurrence. One patient had a previous recurrent myxoma. At surgery we resect all the tumors and their attachment bases. We prefer a biatrial approach, ample resection and exploration of all cardiac chambers. Hospital mortality was 3.7% (1 case of associated aortic valve replacement) and late mortality 7%. Long-term results were satisfactory, without recurrences. The postoperative life expectancy of these patients seems similar to that of the normal population, except in cases of recurrence or associated valve replacement. Recurrence is very low (4.7% in 526 cases reported in the literature), except in the case of young patients and recurrent, familial, multiple or complex myxomas. The multigrowth potential of the tumor seems more important than an inadequate surgical resection. PMID- 8482705 TI - Suitability of Doppler echocardiography for the assessment of right heart hemodynamics after De Vega tricuspid annuloplasty. AB - Cardiac Doppler Echocardiography is a suitable method for to evaluating right heart hemodynamics. However, the surgical correction of tricuspid valve annuloplasty changes valve geometry and might possibly lead to a technical obstacle to this estimation. The accuracy of Doppler echocardiography in the assessment of tricuspid regurgitation and systolic pulmonary pressure in patients who had undergone De Vega annuloplasty was evaluated in this study. Ten patients (9 females and 1 male), mean age 55.7 +/- 7.8 years, who had a previous De Vega annuloplasty for the treatment of tricuspid regurgitation due to a severe mitral stenosis, underwent a Doppler echocardiography study and, within two hours, right heart catheterization for a direct comparison of parameters calculated by different methods. Right ventricular-atrial maximal pressure gradient was found to be 32.6 +/- 11.07 mmHg by Doppler and 31.4 +/- 11.07 mmHg by catheterization. Pulmonary systolic pressure was 42.6 +/- 9.1 mmHg at Doppler and 39.1 +/- 11.3 mmHg at catheterization, with a highly significant correlation between the 2 techniques (r = 0.98%, p < 0.01). With semiquantitative Doppler evaluation 10 patients showed tricuspid insufficiency, which was mild in 8 and medium in 2. At catheterization all patients were found to have mild tricuspid insufficiency. Cardiac Doppler seems a reliable method in the evaluation of tricuspid regurgitation and of pulmonary systolic pressure even in patients who underwent De Vega annuloplasty. PMID- 8482706 TI - An anatomical variation of the right gastroepiploic artery that excludes its use as a pedicled coronary bypass graft. AB - In an attempt to perform complete coronary revascularization with only arterial conduits in a 44 year-old male, both internal mammary arteries and the right gastroepiploic artery were harvested. The right gastroepiploic artery, however, showed an anatomical variation that excluded its use as a pedicled graft. PMID- 8482707 TI - Venous and arteriovenous vascular malformations: diagnostic and therapeutic considerations regarding 239 patients observed in the 1978-1991 period. AB - The Authors report their experience in the treatment of venous and arteriovenous malformations, which in this paper are divided into two subgroups, pure venous malformations (VMs) and arteriovenous malformations (AVMs). A pure surgical indication was evident in less than 50% of cases (48.1%), while more conservative treatments were performed in remaining patients. Considering the particular characteristics of the disease, a complete surgical radicality isn't always possible, so surgery must be considered in selected cases. PMID- 8482708 TI - Total avulsion of the azygos vein and longitudinal laceration of the mediastinal pleura due to blunt chest trauma: a case report. AB - Complete avulsion of the azygos venous arch associated with a subtotal longitudinal laceration of the posterior mediastinal pleura resulting from blunt motor vehicular trauma is reported. A sudden forceful anteromedial rotation of the decelerating cardiac mass may be the etiologic mechanism of the rare injury. PMID- 8482709 TI - Traumatic tricuspid insufficiency following blunt chest trauma. AB - The insufficiency of the tricuspid valve developed due to blunt chest trauma is a rare and an insidiously progressing clinical incident. In this article we present a case which showed tricuspid insufficiency because of the rupture of the anterior papillary muscle due to trauma and which was treated surgically. PMID- 8482710 TI - Mycotic aneurysm of the celiac trunk: radical resection and reconstruction without prosthetic material. AB - The Authors report a case of mycotic aneurysm of the celiac trunk, originating from bacterial endocarditis on the mitral valve. The technique was excision and revascularization without interposition of any material: for the moment it is the first time that a mycotic aneurysm of the celiac trunk is treated in this manner. The post-operative course was normal. PMID- 8482711 TI - A case of cor triatriatum with end-stage renal disease: successful management of open heart surgery under hemodialysis, subsequent renal transplantation and pregnancy. AB - A female patient who had open heart surgery for cor triatriatum under hemodialysis, subsequent kidney transplantation and pregnancy is reported. We performed hemodialysis on the patient before, during and after heart surgery to control renal failure. Two years after heart surgery, she received a kidney graft from her mother. The kidney graft showed good function. She was treated with azathioprine and prednisone. Three years after renal transplantation she delivered a healthy male infant by elective Caesarean section at 37 weeks' gestation. Mother and infant did well following delivery. There was lack of hypertension, proteinuria, signs of graft rejection, and recurrence of heart failure during pregnancy. She showed serum creatinine level < 2 mg/dl, a prednisone of < 2 mg/kg/day. Elective Caesarean section has improved hydronephrosis due to the compression of the fetus. The aforementioned good criteria contributed to the successful pregnancy of the renal transplant patient in our experience. We believe early surgical intervention overcomes complicated heart disease even with endstage renal disease, and it gives a chance to receive renal transplantation and have a healthy child. To our knowledge, this is the first report that has described the successful management of open heart surgery under hemodialysis, subsequent renal transplantation and pregnancy in a female patient with chronic renal failure. PMID- 8482712 TI - Abdominal aortic aneurysmectomy associated with a native iliac kidney. Case report. AB - Abdominal aortic aneurysm (AAA) repair associated with a pelvic kidney is extremely rare. To date only 14 cases have been reported in the literature. The main problem during aortic cross clamping is kidney preservation. The purpose of this article is to record and additional case of AAA repair associated with a native pelvic kidney. The preservation has been successfully achieved by a distal aortic double clamping. PMID- 8482713 TI - Giant left ventricular aneurysm. AB - A 65 year old lady with known inferior left ventricular aneurysm presented with acute dysphagia and hoarseness. A barium swallow examination confirmed extrinsic compression of the oesophagus. Successful aneurysmectomy resulted in complete relief of the dysphagia and hoarseness. The clinical and radiological features are reviewed. PMID- 8482714 TI - Percutaneous embolization of subclavian pseudoaneurysmatic arteriovenous iatrogenic fistula by steel coils. AB - A case of iatrogenic subclavian arterio-venous fistula with pseudoaneurysm formation is described. Treatment by means of percutaneous embolization, on the venous side, with steel coils has been successful; in order to avoid complications, the arterial side was blocked by an angioplasty balloon. After discussing the more common complications of subclavian vein puncture, the Authors conclude that percutaneous embolization is a valuable alternative to surgery even in such a lesion, especially when the surgical risk is high. PMID- 8482715 TI - Neutrophil adhesion to endothelial cells impairs the effects of catalase and glutathione in preventing endothelial injury. AB - We studied the effects of the CuZn superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) on endothelial permeability to 125I-albumin after activation of neutrophils (PMN) with phorbol 12-myristate-13-acetate (PMA; 10(-8) M). PMN were either in direct contact with the endothelial cell monolayer grown on a porous gelatin-coated microporous 10-microns-thick polycarbonate filter (upright system) or separated from the endothelium by a similar filter (inverted system). Transendothelial 125I-albumin clearance rates were measured as an index of endothelial permeability. In the absence of antioxidants, activation of PMN increased transendothelial 125I-albumin clearance rates in both systems from 0.041 +/- 0.006 microliters/min (baseline) to 0.262 +/- 0.18 microliters/min (upright system) and from 0.063 +/- 0.02 microliters/min to 0.244 +/- 0.06 microliters/min (inverted system). PMA induced 80-90% of PMN to adhere to either gelatin-coated filters or to endothelial cells, from the basal PMN adhesion value of 5.3 +/- 2.2% and 4.3 +/- 1.1%, respectively. SOD, which dismutases superoxide anion to hydrogen peroxide (H2O2), did not alter the transendothelial 125I albumin clearance rates in either system at any concentration from 10-300 U/ml. CAT (100-1,000 U/ml) and GSH (0.5-10 mM), which remove the H2O2 generated during PMN activation, did not alter the increase in transendothelial 125I-clearance rates after PMN activation in the upright system, but both agents prevented the increase in transendothelial 125I-clearance rates in the inverted system. We conclude that PMN activation with PMA causes endothelial injury irrespective of PMN contact to the endothelial monolayer. Moreover, H2O2, a release product of PMN activation, is a critical mediator of PMN-dependent endothelial injury. Finally, the results indicate that CAT and GSH prevent endothelial injury only in the absence of direct PMN contact with endothelial cells, suggesting that antioxidants such as GSH and CAT are excluded from sites of PMN-endothelial contact and thus are ineffective antioxidants. PMID- 8482716 TI - Stretch and anesthetic dependency of atrial natriuretic peptide release demonstrated by an ultrastructural assay. AB - Using an ultrastructural assay developed to quantify the secretion of atrial natriuretic peptide-containing granules, release of the hormone, in response to different degrees of atrial distension, is directly demonstrated at the cellular level. The ultrastructural assay developed uses an in situ tannic acid perfusion technique to arrest the exocytosis of atrial granules in the anesthetized rat. Secretory granules, which retain the capacity to undergo exocytosis throughout a 30-minute tannic acid perfusion, accumulate at the cell surface in a state of fusion with the plasma membrane, with the core contents retained. Quantification of arrested granules thus provides a measure of the rate of granule release and allows the responses to different stimuli to be assessed. By altering the height of the perfusate, perfusion pressure and hence the degree of distension of the right atrium can be increased, and this causes a proportional rise in the release of secretory granules from individual myocytes. An anesthetic regime incorporating fentanyl citrate was found to increase significantly the rate of granule release, and this was further augmented by atrial distension. Quantification of the numbers of cytoplasmic granules under the same conditions did not reveal a reduction in granules. This is thought to be because only a small pool of granules is recruited for exocytosis, and granule production may continue during the perfusion period. Our assay of atrial secretory granule release allows the effect of a variety of stimulatory and inhibitory agents to be assessed directly at the cellular level and provides an independent comparison with previous biochemical data from whole animal and isolated organ studies. PMID- 8482717 TI - Inducers of the heat shock response stimulate phospholipase C and phospholipase A2 activity in mammalian cells. AB - Although the mammalian heat shock response has been well characterized, the processes that mediate the induction of the response and the regulation of heat shock protein function are not completely understood. We have investigated the potential role in heat-shocked cells of phosphoinositide-specific phospholipase C (PLC), a membrane enzyme activity involved in transmembrane signal transduction. Our studies indicate that heat shock activates PLC in each of seven cell lines, including cells of human, rat, mouse, and hamster origin. Heat shock produced increases in inositol phosphate concentrations comparable in magnitude to those achieved after simulation with growth factors, indicating that heat shock might initiate transmembrane signaling cascades of potential importance in cellular regulation. Common cellular responses to heat and growth factors also included feedback modulation of PLC by its products and the parallel stimulation of phospholipase A2 activity. In addition to heat shock, other agents that induce the stress response stimulated PLC activity. The data indicate a close correlation between expression of the mammalian heat shock response and stimulation of PLC activity and indicate a possible role for this enzyme activity in the regulation of some aspects of the stress response. PMID- 8482718 TI - Characterization of prostaglandin F2 alpha receptor of mouse 3T3 fibroblasts and its functional expression in Xenopus laevis oocytes. AB - Prostaglandin (PG) F2 alpha increased [3H]thymidine incorporation into quiescent NIH 3T3 cells, stimulated phosphoinositide breakdown, and raised intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner with ED50 values of 2.0 x 10(-8) M, 4.6 x 10(-8) M, and 7.5 x 10(-8) M, respectively. The increase in [3H]thymidine incorporation with PGF2 alpha was additive with that seen with epidermal growth factor (EGF) or insulin. The peak [Ca2+]i increase with PGF2 alpha was still obvious in the absence of extracellular Ca2+ and was insensitive to islet activating protein (IAP) pretreatment. Membranes prepared from NIH 3T3 cells exhibited a specific binding for PGF2 alpha, which was sensitive to GTP gamma S but not sensitive to IAP pretreatment. Xenopus laevis oocytes injected with NIH 3T3 cell mRNA between 18S and 28S rRNA fractionated by sucrose gradient, expressed a PGF2 alpha-specific Cl- current when examined by voltage clamp. This Cl- current was also insensitive to IAP pretreatment and not affected by extracellular Ca2+ concentration ([Ca2+]o). These results indicate 1) that the NIH 3T3 cells expressed a specific PGF2 alpha receptor which is linked to phosphoinositide-specific phospholipase C (PLC) activation and to mobilization of Ca2+ via an IAP-insensitive G-protein(s), 2) that this PGF2 alpha receptor may play an active role in the proliferation of NIH 3T3 cells, and 3) that this PGF2 alpha receptor can be expressed in the oocyte system. PMID- 8482719 TI - Serum-stimulated cell cycle progression and stress protein synthesis in C3H10T1/2 fibroblasts treated with sodium arsenite. AB - In this work, we demonstrated that a nonlethal dose of arsenite administered to quiescent C3H10T1/2 fibroblasts can enhance the mitogenic effect of suboptimal concentrations of serum. The mitogenic effect was dependent on the serum concentration and on the time interval between the administration of arsenite and that of serum. This suggests that mitogen sensitivity changes in time after arsenite treatment. It is shown that the concentrations of arsenite that enhance the mitogenic effect of serum also increase the mRNA levels of c-fos, HSP68, and HSP84 and induce the specific synthesis of Heat Shock Proteins (HSPs). The physiological significance of this phenomenon is most likely to counteract the long-term toxic effect of arsenite by early induction of compensation for cell loss. PMID- 8482720 TI - Follicle-stimulating hormone and human chorionic gonadotropin induced changes in granulosa cell glycosyl-phosphatidylinositol concentration. AB - In the present investigation, a hCG sensitive glycosyl-phosphatidylinositol (GPI) was isolated from cultured rat granulosa cells obtained from the ovaries of diethylstilbestrol (DES) implanted immature rats. The inositol-phosphoglycan (IPG) moiety of the GPI-lipid contains galactose, glucosamine, and myoinositol as demonstrated by metabolic labelling of granulosa cells for different time periods (5-96 h) with [3H]galactose, [3H]glucosamine, or [3H]myoinositol and treatment of the purified [3H]GPI with phosphatidylinositol-specific phospholipase C. Labelling equilibrium of the GPI-lipid was achieved after 24 h ([3H]galactose and [3H]myoinositol) or 72 h ([3H]glucosamine) incubation, whereas incorporation of other labelled carbohydrates tested ([3H]galactosamine, [3H]mannose, and [3H]sorbitol) was negligible throughout the time period studied. The glucosamine C-1 appears to be linked through a glycosidic bond to the myoinositol molecule of the IPG moiety as revealed by the generation of phosphatidylinositol (PtdIns) after nitrous acid deamination of dual labelled ([3H]glucosamine/[14C]palmitate or [3H]glucosamine/[14C]myristate) glycosyl-phosphatidylinositol. To investigate the fatty acid composition of the diacylglycerol (DAG) backbone of the GPI, granulosa cells were also labelled (5-72 hr) with [14C]linoleate, [3H]myristate, [3H]oleate, [3H]palmitate, or [3H]stearate and the radioactivity associated with the purified glycosyl-phosphatidylinositol determined. Incorporation of [3H]palmitate and [3H]myristate into the GPI-lipid peaked after 8 h and 24 h of labelling, respectively, and both fatty acids were partially released after PLA2 treatment of the dual labelled ([3H]glucosamine/[14C]palmitate or [3H]glucosamine/[14C]myristate) GPI. In parallel experiments no significant incorporation of labelled stearate, oleate, or linoleic acid into the DAG backbone of the glycosylphosphatidylinositol could be detected. Granulosa cells were also labelled with [3H]glucosamine in the presence of FSH (30 ng/ml), cholera toxin (1 microgram/ml), or the membrane permeable cAMP analog (but)2cAMP (1 mM). Time related increases in GPI-labelling were apparent after 48 h and reached a maximum level (3-, 5-, and 7-fold for FSH, CT, and (but)2cAMP, respectively) after 72 h in culture. In another set of experiments, granulosa cells were labelled for 72 h with [3H]glucosamine in the presence of (but)2cAMP (1 mM), TPA (10(-7) M), or combination thereof. The effect of treatment with the membrane permeable cAMP analog on GPI labelling was prevented in the presence of TPA, whereas no differences in [3H]GPI content could be observed in untreated granulosa cells or cells cultured in the presence of the protein kinase C activating phorbol ester alone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8482721 TI - CSF-1 control of C-FMS expression in normal human bone marrow progenitors. AB - We have previously shown (Zhou et al: Blood, 72:1870, 1988) that IL3, added with low concentrations of CSF-1 (1 ng/ml) to normal human CD34+ enriched cells, promoted the development of various types of colonies including those containing immature monocytes. However, when high concentrations of CSF-1 (20 ng/ml) were added alone or together with IL3, smaller colonies with mature macrophages were found. Here we show by in situ hybridization that IL3 allows the development, from CD34+ cells, of a subpopulation of immature progenitors which express the CSF-1 receptor (c-fms) mRNA. The expression of c-FMS protein was also substantiated by immunocytochemical studies using anti-c-fms antibody. The percentage of c-fms positive cells peaked at day 7 and began to decrease thereafter. When anti-CSF-1 antibodies were included in the culture, the decrease in c-fms mRNA after day 7 was abrogated. This indicated that endogenous CSF-1 was produced as CD34+ cells developed into monocytes or progenitors of monocytes and that CSF-1 modulates c-fms expression. We further demonstrated that when a high dose of CSF-1 (20 ng/ml) was added at day 7 to IL3-stimulated CD34+ cells, a rapid down-regulation of c-fms mRNA and protein was seen. No down-regulation was observed with low concentration of CSF-1 (1 ng/ml). The possibility that different concentrations of CSF-1 could modulate the development of monocytic progenitors is discussed. PMID- 8482722 TI - Regulation of insulin-like growth factor-IL expression and its role in autocrine growth of human neuroblastoma cells. AB - Insulin-like growth factor-II (IGF-II) is highly expressed in fetal tissues and may act as an autocrine growth factor during early embryogenesis. The SH-SY5Y human neuroblastoma cell line also expresses IGF-II and its receptors and responds to exogenous IGF-II with increased DNA synthesis, cell division, and neuritic outgrowth. For this study, we tested the hypothesis that IGF-II mediates autocrine growth of SH-SY5Y cells in serum-free media. SH-SY5Y cells plated at high densities proliferated in serum-free media, whereas sparsely plated cells did not. IGF-II mRNA levels increased within 24 hours of serum deprivation and were associated with increased immunoreactive IGF-II protein. Exogenous addition of IGF-II increased 3H-TdR incorporation and cell number in a dose- and time dependent fashion. By nuclear labelling experiments using 5-Bromo-2' deoxyuridine (BrdU), we detected a twofold higher percentage of S phase nuclei after a 24-hour incubation in IGF-II. Treatment of SH-SY5Y cells with anti-IGF-II antibodies in serum-free media inhibited cell proliferation, and this inhibition was partially overcome by the addition of increasing concentrations of IGF-II. Collectively, our results indicate that IGF-II mediates an autocrine growth mechanism in SH SY5Y cells that is associated with increased IGF-II expression. PMID- 8482723 TI - Protein kinase inhibitor, staurosporine, induces a mature neuronal phenotype in SH-SY5Y human neuroblastoma cells through an alpha-, beta-, and zeta-protein kinase C-independent pathway. AB - Previous studies have shown that the tumour-promoting phorbol ester 12-O tetradecanoyl phorbol-13 acetate (TPA) induces both morphological and functional differentiation in SH-SY5Y human neuroblastoma cells (Pahlman et al., 1981). In order to investigate the role of protein kinase C (PKC) in TPA-induced maturation of SH-SY5Y cells, we have used staurosporine, which is a potent inhibitor of protein kinases including PKC. Treatment of SH-SY5Y cells with 25 nM staurosporine for 72 hours caused an appearance of long, neuritelike processes with varicosities, terminated by growth cones. The morphological differentiation was accompanied by a cessation of DNA synthesis, induction of growth associated protein 43 (GAP-43), and neuropeptide Y (NPY) mRNA. These effects of staurosporine were comparable to those elicited by TPA. Staurosporine further induced a time-dependent increase in the expression of tyrosine hydroxylase protein and a 30-fold increase in the concentration of noradrenaline. TPA only induced a marginal increase in tyrosine hydroxylase expression. Both TPA and staurosporine induced an appearance of voltage-gated Ca2+ channels in SH-SY5Y cells detected with single-cell fluorescent measurements using fura-2. The Ca2+ channels were found almost exclusively in growth cones and varicosities. Staurosporine inhibited both basal and a TPA-induced phosphorylation of an endogenous 80kDa PKC substrate (p80), and also blocked c-fos proto-oncogene mRNA expression induced by the phorbol ester. Bryostatin 1, a potent activator of PKC, has failed to induce morphological or functional differentiation in SH-SY5Y cells (Jalava et al., 1990). Incubation of SH-SY5Y cells in the presence of 100 nM bryostatin 1 for 24 hours caused a complete disappearance of all immunoreactive alpha-, beta-, and zeta-PKC. The level of epsilon-PKC decreased by 70%. Staurosporine induced a partial translocation of the epsilon-isoenzyme but it failed to cause down-regulation of epsilon-PKC. Bryostatin 1-treatment did not interfere in the ability of staurosporine to induce morphological differentiation, cessation of DNA synthesis, and GAP-43 and NPY mRNA expression. The ability of staurosporine to stimulate tyrosine hydroxylase expression and to increase cellular content of noradrenaline was also unaffected. Taken together the results of this study show that staurosporine induces a mature neuronal noradrenergic phenotype in SH-SY5Y cells through an alpha-, beta-, and zeta-PKC independent pathway. PMID- 8482724 TI - Mechanism of retinoid-induced activation of latent transforming growth factor beta in bovine endothelial cells. AB - Cell-associated plasmin is a putative physiological activator of latent transforming growth factor-beta (LTGF-beta). Since retinoids enhance the production of plasminogen activator (PA) and thereby increase cell-associated plasmin activity, we tested the possibility that retinoids might induce the activation of LTGF-beta using bovine endothelial cells (ECs) as a model system. ECs treated with physiological concentrations of retinol or retinoic acid formed active TGF-beta in the culture media in a dose- and time-dependent fashion. Cells were treated with 2 microM retinol for 24 h, and the amount of TGF-beta produced during a subsequent 12-h incubation period was measured. Out of a total of 14 pM LTGF-beta secreted, 0.7 pM was converted to active TGF-beta. Northern blot analyses showed that mRNA levels for TGF-beta 2 but not for TGF-beta 1 increased in cells treated with retinol. Inclusion of either inhibitors of PA or of plasmin or antibody against PA in the culture medium as well as depletion of plasminogen from the serum blocked the formation of TGF-beta, suggesting that PA, plasminogen, and the resulting plasmin are essential for activation of LTGF-beta in retinoid-stimulated cells. Antibody against the LTGF-beta binding protein blocked activation implying that localization of LTGF-beta through its binding protein may be important. However, inhibition of binding of LTGF-beta to the cell surface mannose 6-phosphate receptor did not prevent activation. These data indicate that retinoids up-regulate the production of LTGF-beta in ECs and induce activation of LTGF-beta, perhaps, by increasing PA and plasmin levels. Thus, TGF beta might be a local mediator of some of the biological activities of retinoids both in vivo and in vitro. PMID- 8482725 TI - Autocrine/paracrine regulation of keratinocyte urokinase plasminogen activator through the TGF-alpha/EGF receptor. AB - Transforming growth factor-alpha (TGF-alpha) appears to be an important autocrine/paracrine regulator of keratinocyte function. Not only does TGF-alpha induce keratinocyte proliferation and migration in vitro, but it also has been detected in normal human epidermis and at elevated levels in hyperproliferative epidermis. In the present study we report that exogenous TGF-alpha increases urokinase-type plasminogen activator (uPA) in cultured human keratinocytes. Furthermore, in the absence of exogenous growth factors, the "basal" levels of uPA are decreased by an antagonist monoclonal antibody to the receptor shared by TGF-alpha and epidermal growth factor (EGF). These results suggest that an endogenous factor serves as an autocrine/paracrine regulator of keratinocyte uPA. We hypothesize that activation of the TGF-alpha/EGF receptor may coordinately regulate the keratinocyte response to cutaneous wounding, which includes enhanced uPA expression, migration, and proliferation. PMID- 8482726 TI - Mevalonate controls cytoskeleton organization and cell morphology in thyroid epithelial cells. AB - Blockade of mevalonate synthesis by the 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor mevinolin (lovastatin) causes FRTL-5 thyroid cells to undergo significant morphological changes; these include a transition from a flat, polygonal to a round shape, the development of cytoplasmic arborizations, and the loss of contact between neighboring cells. Immunofluorescence studies of cytoskeletal structures show that, at early times after administering the drug, and before the round phenotype develops, stress fibers disassemble while the peripheral actin filaments, which are adjacent to the cytoplasmic face of the plasma membrane, appear largely unaffected. Subsequently, when this cortical actin network becomes fragmented, cells start to round up and become separated from neighbors. Microtubules become disconnected from the plasma membrane and retract toward the cell center, although they do not appear depolymerized; indeed, at this stage, cytoplasmic elongations contain mostly intact microtubules. After exposure to mevinolin FRTL-5 cells also lose vinculin-related substrate contacts. Treatment of cells with either cycloheximide or colchicine abolishes morphological changes induced by mevinolin, suggesting that ongoing protein synthesis and microtubule integrity are prerequisites for the drug to be effective. Both cytoskeletal and morphological perturbations can be reversed by mevalonate, but not by cholesterol or the non-sterol derivatives of mevalonate such as dolichol, ubiquinone, and isopentenyladenine, individually or in combination. It is suggested that mevalonate deficiency may impair formation of isoprenylated proteins important for cytoskeletal organization and stability. PMID- 8482727 TI - Expression and loss of the transferrin receptor in growing and differentiating HD3 cells. AB - During induced differentiation and maturation of HD3 cells (a chicken erythroblast cell line infected with a temperature-sensitive mutant of the avian erythroblastosis virus), the levels of transferrin receptor (TFR) and nucleoside transporter increase. Both these activities increase before elevated levels of hemoglobin are detected. Shortly after induction, as cellular TFR levels rise, a native-size TFR is detected in the cell-free culture medium, associated with an exosome fraction (100,000 xg pellet). Nucleoside transporter (measured as NBMPR binding activity) is not increased in this pellet with induction. Previous studies have suggested that exosome formation in peripheral reticulocytes may be a significant route for loss of specific membrane proteins (Johnstone et al., 1991). Although the present experiments in HD3 cells do not address the quantitative importance of exosome formation, the studies suggest that exosome formation is an early event in commitment to the red cell lineage and is not a phenomenon restricted to the terminal stages of red cell maturation. PMID- 8482728 TI - Fibroblast contraction of collagen gels requires activation of protein kinase C. AB - Fibroblasts stimulated to contract collagen gels with serum were completely inhibited by staurosporine, a broad spectrum kinase inhibitor. Further analysis demonstrated that staurosporine is potent (IC50 17 nM), rapid in onset, and completely reversible. Complete inhibition of gel contraction was also observed with calphostin C (IC50 48 nM), an inhibitor specific for protein kinase C (PKC). Similar effects were not observed with KT5926 or KT5720, inhibitors for myosin light chain kinase and cAMP-dependent kinases, respectively. These data suggested that serum-stimulated fibroblast contraction is dependent upon activation of PKC. This was also observed with fibroblast contraction stimulated with endothelin-1, platelet-derived growth factor, and transforming growth factor beta. PKC activated directly with low concentrations of phorbol ester was observed to stimulate fibroblast contraction of collagen gels, in some cases within 30 minutes of exposure. PMID- 8482729 TI - Growth state-regulated expression of p52(PAI-1) in normal rat kidney cells. AB - In normal rat kidney (NRK) cells, synthesis of the 52-kDa substrate-associated type 1 inhibitor of plasminogen activator [p52(PAI-1)] is linked to alterations in cell shape and substrate adhesion. Subconfluent NRK cells accumulated significantly more ventral undersurface-associated p52(PAI-1) compared to newly confluent or 1-to 2-day postconfluent cultures, suggesting that p52(PAI-1) expression was also growth state-modulated. Since cytoarchitectural constraints function in cell growth control, changes in p52(PAI-1) synthesis were assessed with respect to defined morphologic events that accompany growth activation of cultured NRK cells. Stimulation of low population density, quiescent NRK cells with 20% serum-containing medium resulted in a rapid increase in matrix p52(PAI 1) protein content (6- and 26-fold after 1 and 5 hr, respectively). Growth activation in response to serum reflected activations in p52(PAI-1) cytoplasmic mRNA abundance, which peaked at 2 hr (125-fold increase) and subsequently declined (100-fold increase) at 5 hr poststimulation. Morphologic analysis indicated that quiescent NRK cells were devoid of transcytoplasmic actin filaments and focal contact-associated vinculin. A marked increase in the fraction of cells that elaborated transcytoplasmic microfilaments and vinculin containing focal adhesions was evident within 5 min of serum addition. Such cytoarchitectural restructuring preceded p52(PAI-1) induction. Morphologic reorganization and p52(PAI-1) induction occurred prior to progression of cells through the S-phase, indicating they are early events associated with serum stimulation in the NRK cell system. The relevance of p52(PAI-1) induction during this growth state transition is not clear but may influence the established cytoarchitectural changes observed prior to p52(PAI-1) induction by regulating pericellular proteolysis and, thereby, cell-to-substrate adhesion. PMID- 8482730 TI - Pericyte growth and contractile phenotype: modulation by endothelial-synthesized matrix and comparison with aortic smooth muscle. AB - We compared the effects of endothelial-synthesized matrix and purified matrix molecules on pericyte (PC) and aortic smooth muscle cell (SMC) growth, heparin sensitivity, and contractile phenotype in vitro. When PC are plated on endothelial-synthesized (EC) matrix, cell number is, on average, 3.1-fold higher than identical populations grown on plastic. Under the same conditions, SMC proliferation is stimulated 1.6-fold. Purified matrix molecules, such as collagen type IV (COLL) or fibronectin (FN), both major components of the EC matrix, stimulate PC/SMC growth 1.2-1.7-fold. Heparin (100 micrograms/ml), which inhibits the growth of early passage SMC by 60%, inhibits PC growth approximately 50%, when cells were plated on plastic. However, PC plated on EC matrix in the presence of heparin (100 micrograms/ml) grow as well as parallel cultures grown on plastic (in the absence of heparin). Concomitant with matrix-stimulated proliferation, we observed a marked reduction in PC containing alpha vascular smooth muscle actin (alpha VSMA), as seen by immunofluorescence using affinity purified antibodies (173/615 positive pericytes on DOC matrix (28%) vs. 221/285 (77%) positive on glass). SMC respond similarly. Whereas alpha VSMA protein is markedly altered when PC and SMC are cultured on EC matrix, similar reductions in mRNA are not observed. However, Northern blotting does reveal that PC contain 17 30 times the steady-state levels of alpha VSMA mRNA compared to SMC. When SMC and PC cultures on plastic are treated with heparin, the steady-state levels of vascular smooth muscle actin mRNA increase 5 and 1.5 fold, respectively. Similarly, heparin treatment of PC grown on plastic induces a 1.8 fold increase in nonmuscle actin mRNA. These heparin-induced alterations in isoactin mRNA levels are not seen when PC are cultured on EC matrix. We also observed reductions in alpha VSMA and beta actin mRNA levels when PC are plated on FN, where they maintain a ratio of 13:1 (alpha:beta). Similar ratios are found in SMC present in rat and bovine aortae in vivo. These steady-state isoactin mRNA ratios are slightly different from those seen in cultured PC (8-10:1; alpha:beta). These results suggest that selective synthesis and remodelling of the endothelial basal lamina may signal alterations in pericyte growth and contractile phenotype during normal vascular morphogenesis, angiogenesis, or during the microvascular remodelling that accompanies hypertensive onset. PMID- 8482731 TI - Effect of phospholipid acyl chain modulation on vitamin E incorporation into pulmonary artery endothelial cell membranes. AB - Incorporation of vitamin E (alpha-tocopherol) was measured in total membranes of pulmonary artery endothelial cells (PAEC) following treatment with eight synthetic phosphatidylethanolamines (PE) (Palmitoyloleoyl, 16:0-18:1 PE1; distearoyl, 18:0-18:0 PE2; dioleoyl, 18:1-18:1 PE3; stearoyl- linoleoyl, 18:0 18:2 PE4; dilinoleoyl, 18:2-18:2 PE5; stearoyl-arachidonyl, 18:0-20:4 PE6; diarachidonyl, 20:4-20:4 PE7; and stearoyl-docosahexenoyl, 18:0-22:6 PE8). Endogenous PE content of native membranes was 0.88 +/- 0.01 nmol/mg protein. Incorporation of PE irrespective of fatty acid content significantly (P < 0.02) increased the PE content of total membranes. Vitamin E incorporation in control membranes was 63 +/- 9 nmol/mg protein. Incorporation of vitamin E in PE1- to PE7 treated cells were significantly (P < 0.05) increased compared to controls and were comparable to each other. Vitamin E incorporation into PE8-treated cells was threefold greater (P < 0.001) than controls and twofold greater (P < 0.001) than PE1- to PE7-treated cells. Increased PE content results in increased vitamin E incorporation into PAEC membranes irrespective of the fatty acids present on the acyl chain, and maximal incorporation of vitamin E in PE8-treated cells may relate to the increased carbon chain length rather than to the degree of unsaturation at the sn2 position. PMID- 8482732 TI - Regulation of polyamine transport by polyamines and polyamine analogs. AB - Regulation of polyamine transport in murine L1210 leukemia cells was characterized in order to better understand its relationship to specific intracellular polyamines and their analogs and to quantitate the sensitivity by which it is controlled. Up-regulation of polyamine uptake was evaluated following a 48-hr treatment with a combination of biosynthetic enzyme inhibitors to deplete intracellular polyamine pools. The latter declined gradually over 48 hr and was accompanied by a steady increase in spermidine (SPD) and spermine (SPM) transport as indicated by rises in Vmax to levels approximately 4.5 times higher than control values. Restoration of individual polyamine pools during a 6-hr period following inhibitor treatment revealed that SPD and SPM uptake could not be selectively affected by specific pool changes. The effectiveness of individual polyamines in reversing inhibitor-induced stimulation of uptake was as follows: putrescine < SPD < SPM = the SPM analog, N1, N12-bis(ethyl)spermine (BESPM). In contrast to stimulation of transport, down-regulation by exogenous polyamines or analogs occurred rapidly and in response to subtle increases in intracellular pools. Following a 1-hr exposure to 10 microM BESPM, Vmax values for SPD and SPM fell by 70%, whereas the analog pool increased to only 400-500 pmol/10(6) cells- about 15-20% of the total polyamine pool (approximately 2.8 nmol/10(6) cells). SPM produced nearly identical regulatory effects on transport kinetics. Both BESPM and SPM were even more effective at down-regulating transport that had been previously stimulated four to fivefold by polyamine depletion achieved with enzyme inhibitors. A dose response with BESPM at 48 hr revealed a biphasic effect on uptake whereby concentrations of analog < 3 microM produced an increase in SPD and SPM Vmax values, whereas concentrations 3 microM and higher produced a marked suppression of these values. Cells treated with 3 microM BESPM for 2 hr and placed in analog-free medium recovered transport capability in only 3 hr. Thus, whereas stimulation of polyamine transport is a relatively insensitive and slowly responsive process that tends to parallel polyamine depletion, down-regulation of polyamine transport by exogenous polyamines and analogs and its reversal are rapidly responsive events that correlate with relatively small (i.e., 15-20%) changes in intracellular polyamine pools. PMID- 8482733 TI - Defensins are mitogenic for epithelial cells and fibroblasts. AB - Defensins are a family of structurally homologous peptides contained within phagocytic cells. Although these peptides are best known for their broad spectrum antimicrobial properties, they also inhibit ACTH (corticotropin) stimulated corticosterone production, chemoattract monocytes, and lyse mammalian cells. We now report that these peptides are potent mitogens in vitro in the same concentration range that they display potent antimicrobial activity in vitro. These concentrations are in the same range as those expected to be present in vivo during the wound healing process. All defensins tested were stimulatory for epithelial cells and fibroblasts and acted synergistically with insulin. These are the first data to disclose the strong growth-promoting effects of this unique family of peptides and point to another basic mechanism whereby the macrophage and neutrophil may participate in a variety of trophic, physiologic, and pathologic processes. PMID- 8482734 TI - Statement of the Coalition for Oral Health. PMID- 8482735 TI - Inclusion of oral health into the National Health Care Reform Program. PMID- 8482736 TI - Mentoring the individual student: qualities that distinguish between effective and ineffective advisors. PMID- 8482737 TI - Supporting Student Research Group activities. PMID- 8482738 TI - A student's expectations of the research experience. PMID- 8482739 TI - Supporting student research at the administrative level. PMID- 8482740 TI - Mentoring during the transition from graduate student to faculty member. PMID- 8482741 TI - Pre-admission credentials and dental school performance of dental hygienists. AB - This study examined the effect of dental hygiene preparation prior to entering dental school on dental school performance. Study participants included 203 female students who entered a public dental school from 1980-1989. Groups 1 and 2 had completed dental school prerequisites and a dental hygiene curriculum in a community college setting (n = 19) or university setting (n = 22) respectively, and Group 3 (n = 162) were traditional students with no dental hygiene education. Preadmission variables were predental science and non-science grade point averages (GPA) and Dental Admission Test (DAT) scores. Performance variables were GPA of years one and two of dental school and National Board scores (Part 1). Results showed that Group 2 hygienists had significantly lower predental science GPAs than Group 1 or 3 and significantly lower non-science GPAs than Group 3 (p < 0). Both groups of hygienists had significantly lower DAT scores than Group 3 (p < 0). No difference was seen in first and second year GPAs or the National Board average. Adjusting performance scores to compensate for deficiencies in preadmission variables showed that Group 2 hygienists had significantly higher adjusted first-year GPAs and National Board averages than Group 3 (p < 0). Thus, hygienists performed as well as non-hygienists in spite of weaker admission credentials. PMID- 8482742 TI - Preclinical operative dentistry courses in northern Europe and Scandinavia. PMID- 8482743 TI - A survey of faculty practice plans in United States and Canadian dental schools. PMID- 8482744 TI - Statement of the American Association of Dental Schools on the future of the NIDR Intramural Research Program. PMID- 8482745 TI - Curriculum guidelines on oral and maxillofacial surgery. American Association of Dental Schools. PMID- 8482746 TI - Quantitative analysis of stratum corneum lipids in xerosis and asteatotic eczema. AB - Sphingolipids, a major constituent of intercellular lipids, are an important determinant for both water-holding and permeability barrier function in the stratum corneum. To assess the pathogenic role of sphingolipids in the stratum corneum of dry skin disorders such as xerosis and asteatotic eczema in leg skin, ceramides were quantified by thin layer chromatography after n-hexane/ethanol extraction of resin-stripped stratum corneum and evaluated as micrograms/mg stratum corneum. In healthy leg skin (n = 49), there was age-related decline in the total ceramide, whereas xerosis (n = 25) and asteatotic eczema (n = 16) suffering significantly reduced water-holding properties, exhibited no definite decrease, rather slight increase in ceramide quantity with the same composition of each individual ceramide as compared to healthy age-matched controls. These data indicate that the seemingly elevated level of ceramide is an artificial effect due to inflammatory processes which result from susceptibility to dryness. Analysis of sebum-derived lipids present in the stratum corneum revealed that there was a significant decline in free fatty acids in xerosis and asteatotic eczema as compared to age-matched healthy controls, and a similar decline in triglycerides in the above three groups when compared to younger controls. Although the observed decrease in the stratum corneum lipids may well explain the high incidence of winter dry skin in older people, the progression toward asteatotic eczema can not be accompanied solely by a decrease in ceramide quantity, suggesting that the evolution of xerotic skin is associated with other moisturizing factors and/or environmental stimuli. PMID- 8482747 TI - Evaluation of phenolic glycolipid-I (PGL-I) antibody as a multidrug therapy (MDT) monitor. AB - Since phenolic glycolipid-I (PGL-I) is an unequivocal marker for Mycobacterium leprae, this antigen has been a good candidate for the serodiagnosis and monitoring of the effectiveness of leprosy chemotherapy. The present study, a continuation of an earlier report, was undertaken to estimate PGL-I antibody titers in 40 leprosy patients 3 and 6 months after starting MDT. All the leprosy groups showed significant declines in anti PGL-I reactivity after 6 months. There was a good correlation between bacteriological indices (BI) and anti PGL-I antibody levels. Thus, PGL-I based serology may be useful in monitoring the response to multidrug therapy. PMID- 8482748 TI - Analyses of serum copper and zinc levels and copper/zinc ratios in skin diseases. AB - With the objective of comprehending abnormal metabolisms of the essential metals of zinc (Zn) and copper (Cu) in three groups of skin diseases, skin cancer, inflammatory diseases, and non-inflammatory disease, we measured serum levels of Zn and Cu in 151 cases of various cutaneous manifestations and estimated the significance of the ratios between the two metals (Cu/Zn). The serum level of Zn was significantly decreased in cases of bullous pemphigoid, decubitus ulcer, and alopecia areata. The serum level of Cu was elevated in cases of psoriasis, decubitus ulcer, and skin cancer. We observed no elevation of serum Zn level or abnormally depressed serum Cu level. The Cu/Zn ratio showed significantly different values among these three groups of the diseases, suggesting the utility of measuring Cu/Zn ratios for differential diagnosis over that of determining the serum level of Zn or Cu alone. It was also demonstrated that, in each skin disease, the Cu/Zn ratio clearly reflects the severity of the progress. PMID- 8482749 TI - Analysis of lymphocyte subpopulations in peripheral blood in adult and juvenile cases of dermatomyositis. AB - Dermatomyositis, recognized as an autoimmune disorder, occurs not only in adults but also in children. In this study, we evaluated lymphocyte subpopulations in the peripheral blood of 24 adult dermatomyositis and 14 juvenile dermatomyositis patients and in 17 healthy adults and 9 healthy children by flow cytometry using monoclonal antibodies. When compared with healthy adults and adult patients with inactive dermatomyositis, the adult patients with active disease had significantly lower percentages of CD3+ and CD8+ cells and a significantly higher percentage of CD20+ cells. In contrast, juvenile dermatomyositis patients had lymphocyte subpopulations not significantly different from those of healthy children; the activity/inactivity of disease did not make any difference. These results support our hypothesis that adult and juvenile dermatomyositis may be diseases of entirely different scope. PMID- 8482750 TI - Electron-microscopic observation of a human epidermal Langerhans cell in mitosis. AB - Langerhans cells are dendritic cells of the epidermis originating from bone marrow precursors which may exceptionally undergo mitosis within the skin. We report herein an electron-microscopic observation of a dividing LC within a seemingly hyperproliferative human epidermis. This observation further underlines the self-reproducing capacity of LC in situ and suggests that LC may respond to the same mitogenic stimuli as keratinocytes. PMID- 8482751 TI - A case of progressive systemic sclerosis associated with sarcoidosis and esophageal adenocarcinoma. AB - A 50-year-old Japanese female with progressive systemic sclerosis (PSS, CREST syndrome) is reported. During treatment for PSS, she was diagnosed by clinical and laboratory findings as having sarcoidosis, which was confirmed by histological examination of the skin and lymph nodes in July of 1991. She complained of back pain in August of 1991. Reflux esophagitis and Barrett's esophagus, found by endoscopy, progressed into a well-differentiated tubular adenocarcinoma. This is a very rare case of PSS associated with sarcoidosis and esophageal adenocarcinoma developing from Barrett's esophagus. PMID- 8482752 TI - Erythroderma, hair loss, and sinus histiocytosis with massive lymphadenopathy in a XYY-male. AB - This paper presents a case of sinus histiocytosis with massive lymphadenopathy (SHML) presenting as erythroderma in an XYY-male aged 27. The patient had little or no scalp, axillary, or pubic hair. Histologically, lymph nodes indicated dilatation of the sinuses with proliferation of benign-appearing histiocytes possessing abundant clear cytoplasm, admixed with giant cells and pericapsular fibrosis. Infiltrating histiocytes in the lymph nodes were OKM-1 (CD11b) positive, which is characteristic of monocyte-granulocyte lineages. In the present case, the abnormal presence of erythroderma, hair loss, SHML, and a chromosomal abnormality, XYY, were thought to be incidental features. PMID- 8482753 TI - Dyskeratosis congenita: a case report. AB - Dyskeratosis congenita, an uncommon situation in females, is described in a 30 year-old woman. The expression of the disease was partial and was characterized by mottled pigmentation, nail dystrophy, palmoplantar keratoderma, and hyperhidrosis. PMID- 8482754 TI - Acral lentiginous melanoma associated with Down's syndrome. PMID- 8482755 TI - Granulomatous tissue reaction and calcification of heterologous elastin implanted in hairless mouse skin: light and electron microscopic studies compared with reaction of heterologous collagen. AB - Heterologous elastin particles were injected into the deep dermis or below the panniculus carnosus of hairless mice. A granulomatous tissue reaction with concomitant giant cell formation occurred around the implanted elastin in the early stages and, subsequently, calcium deposition with disappearance of the histiocytes and giant cells occurred in the later stages. Ultrastructural study revealed that some elastin particles were engulfed by the giant cells; others underwent calcification but remained intact. The heterologous collagen used as a control also induced a granulomatous tissue reaction, but did not undergo calcification and gradually disappeared. These results suggest that the heterologous elastin and collagen particles exhibit different susceptibilities to digestion. However, it is not clear why the heterologous elastin underwent calcification. PMID- 8482756 TI - Reduction in sexual risk behaviors among college students following a comprehensive health education intervention. AB - Sexually active college students are at risk of contracting sexually transmitted diseases, including HIV infection. As a result, health education initiatives to prevent these infections are commonplace, but few controlled research studies have evaluated behavioral changes as a result of on-campus sex education. In a nonrandomized control trial, sexual risk behaviors of 341 students who had received a comprehensive health education intervention in a first-year seminar were compared with 227 students who were not enrolled in the seminar. The seminar curriculum included an intervention addressing facts about sexually transmitted diseases, safer sex, values, decision making, and assertiveness skills. Sexual abstinence (no sexual intercourse), number of sexual partners, consistent condom use, and methods of contraception were assessed at baseline and after 3 months. Compared with students who had not received the intervention, men in the seminar reported increased sexual abstinence but no change in consistent condom use; the women in the intervention group reported no change in sexual abstinence but an increase in consistent condom use. Women who had not received the intervention reported never using a condom more frequently than women who had received the intervention. The health education intervention on a college campus was associated with short-term reduction in sexual risk behaviors, but the reduction varied according to the students' gender. PMID- 8482757 TI - Using focus group interviews to identify salient issues concerning college students' alcohol abuse. AB - Despite extensive efforts to decrease alcohol abuse among college students, prevention approaches have had limited success. This study attempted to clarify reasons for this limited success and to identify directions for future interventions by directly interviewing college students on this topic. Five issues were discussed in the focus group interviews: (1) reasons for drinking alcohol, (2) reasons for not drinking alcohol, (3) circumstances surrounding overconsumption of alcohol, (4) topics and methods for prevention, and (5) gender differences in drinking patterns. The focus group interviews were found to be a valid tool for elucidating sensitive aspects of these issues and the relative importance of these issues to each other. The students revealed how susceptible they are to societal pressures to drink alcohol and how the limitations of their intrapersonal skills affect their alcohol consumption, most notably regarding sexuality issues. The authors contend that improving intrapersonal skills should be a major focus of programs to prevent alcohol abuse. PMID- 8482758 TI - HIV prevention among Asian-American college students: does the health belief model work? AB - This study examined the predictive utility of the health belief model (HBM) in relation to prevention of HIV infection among Asian-American college students. Four research hypotheses were proposed. Three of these hypotheses proposed a positive relationship between perceived susceptibility, severity, and benefits, and HIV-preventive behavior. The fourth research hypothesis postulated a negative relationship between perceived barriers to prevention and actual HIV-preventive behaviors. Results indicated that severity and barriers are significant predictors of the adoption of HIV-preventive behaviors among Asian-American students. Severity was a significant predictor of becoming more careful about the selection of intimate partners, reducing the number of sexual partners, and generally positive changes toward safer sexual behavior, whereas barrier was a significant predictor of becoming more careful about the selection of intimate partners, reducing the number of sexual partners, and ensuring that sexual partners are not HIV infected. It also appeared that cultural factors, such as beliefs about HIV, illness, prevention, sexuality, and homosexuality, need to be incorporated into tests of the model to enhance its predictive power. Implications of the results and suggestions for further research are discussed. PMID- 8482759 TI - Effectiveness of a college course focused on evaluation of health claims. AB - This study measured the effectiveness of a college course designed to instruct students to make critical evaluations of therapeutic claims for foods, nutrient supplements, weight-reduction products and diets, and alternative healthcare systems. Experimental and comparison groups were pretested and posttested to determine changes in source reliance and cognitive learning. The experimental group received instruction in five cognitive areas: (1) health and nutrition quackery, (2) consumer protection, (3) basic concepts in health and nutrition, (4) nutritional supplements and health foods, and (5) conventional and unconventional treatment of chronic diseases. The experimental group scored significantly higher in all five conceptual areas on the posttest, and in each case scored significantly higher than the comparison group did. Both groups rated medical/scientific sources of health and nutrition information as highly accurate during the two survey periods. The experimental group showed a change in source reliance, moving from dependence on the popular print media and individuals without formal education in a health field to medical/scientific sources, whereas the comparison group continued to use the popular press and electronic media. Findings suggest that a source targeted to the needs and interests of a specific group can bring about significant increases in knowledge gain and desirable changes in source reliance. PMID- 8482760 TI - Comparison of the cytology brush with the Dacron swab for detecting Chlamydia trachomatis by enzyme immunoassay in female university students. AB - Previous studies comparing the cytology brush (Cytobrush) with swabs for the detection of Chlamydia trachomatis from the uterine cervix have yielded divided results. The authors carried out a retrospective analysis at the University of South Florida Student Health Service to evaluate the effect of a change in specimen collection technique on C trachomatis prevalence estimates in female university students. Samples were collected from 1,003 women in 1989, using a small Dacron swab, and 1,229 women in 1990, using a brush; the samples were tested by means of the Pathfinder Enzyme Immunoassay (EIA) detection kit. Positive test results were 5.88% for 1989 and 11.66% for 1990. Actual C trachomatis prevalence for 1989 and 1990 was stable, as determined by three control groups. The results suggest that the cytology brush is more effective than the Dacron swab for the detection of C trachomatis in the uterine cervix when it is used with the Pathfinder EIA test kit. PMID- 8482761 TI - Noninvasive detection of Chlamydia trachomatis in men: a comparison of two immunoassay tests. AB - This investigation compared a rapid enzyme immunoassay test and an enzyme amplified immunoassay test with culture for the noninvasive detection of Chlamydia trachomatis urethritis in men. Urine specimens from 108 male subjects were evaluated for the presence of C trachomatis antigen, using the Kodak Surecell Chlamydia rapid enzyme immunoassay test and IDEIA Chlamydia enzyme amplified immunoassay test. The test results were then compared with urethral C trachomatis culture and urethral Gram's stain analyses. Performance characteristics of the two tests were similar. The rapid chlamydial enzyme immunoassay test demonstrated several clinical advantages. Appropriate use of these tests may decrease patient morbidity and clarify organism etiology for enhanced specific medical care of urethritis in men. PMID- 8482762 TI - Students and other patients. PMID- 8482763 TI - Establishing a student health all-appointment system: making the transition from a walk-in approach. AB - The authors offer a process for critically evaluating a walk-in system for patient and care provider satisfaction, for developing goals for a new patient flow system, and for designing and implementing an appointment system at a student health center. Their suggestions are based on their recent experience in making the transition from a walk-in approach to an all-appointment system in the general medicine division of the university's student health service. They give specifics of the appointment system established at their facility, including an explanation of the weekly appointment schedule, the monthly duty schedule, and a strong triage system. Key areas for consideration in converting to an all appointment system, such as reeducational techniques for various staffing responsibilities and strategies for marketing a new system to patients, are outlined in detail. PMID- 8482764 TI - Responding to student disruptions: incorporating supported education. PMID- 8482765 TI - An abstract error? PMID- 8482766 TI - Boosting practice activity and patient service. PMID- 8482767 TI - Assessing quality in dentistry: dental boards, peer review vary on disciplinary actions. AB - Reported inconsistencies in entry level exams and variations in available disciplinary mechanisms suggest the need for modifications to improve these processes. A quality assurance system combining education with some sanctions is likely to engender dentist support and improve quality of care. PMID- 8482768 TI - Lasers issue lauded. PMID- 8482769 TI - A note on nitrous. PMID- 8482770 TI - Pricing and the perception of health care service quality. AB - Do patients bargain-hunt when choosing a dentist or physician? Perceptions of quality, price and a patient survey are discussed. PMID- 8482771 TI - Maxillary sinus grafting for totally and partially edentulous patients. AB - The presence of the maxillary sinus and lack of adequate bone to stabilize the implants could make traditional implant placement impossible. The solution includes grafting bone to the posterior maxilla to provide adequate bone support for implant integration and long-term survival. PMID- 8482772 TI - CAD-CAM comments. PMID- 8482774 TI - Court stops Florida from recognizing Alabama hygiene program. PMID- 8482773 TI - Court says surgeon should have disclosed HIV status. PMID- 8482775 TI - When is a dentist an employee? PMID- 8482776 TI - Anxiety can increase post-surgical complications. PMID- 8482777 TI - WSDA issues consumer checklist. PMID- 8482778 TI - NYU Kriser Dental Center receives grant to help AIDS patients. PMID- 8482779 TI - Current concepts in dentin bonding: focusing on dentinal adhesion factors. AB - With greater need for treating root surface lesions, dentinal adhesives are more in demand. For successful treatment, all factors--dentin, tooth, patient and materials--must be considered. PMID- 8482780 TI - Current developments in dentin bonding systems: major progress found in today's products. AB - The procedures and products used in dentin bonding systems have changed over the years. An overview of the evolving systems is provided. PMID- 8482781 TI - How dentists classified and treated non-carious cervical lesions. AB - All North Carolina general dentists were shown color photographs of three non carious cervical lesions. A fourth picture showed cervical caries. Respondents were asked how they defined each lesion, its cause, treatment and frequency of appearance in practice. Cervical caries was identified and treated by almost all responding dentists, but they applied more varied terms, causes and treatments to non-carious defects. PMID- 8482782 TI - Determining amalgam marginal quality: effect of occlusal surface condition. AB - Currently there is no "standard" finishing and polishing procedure for dental amalgam restorations. This investigation evaluated the effect of four different finishing techniques on the durability of dental amalgam restorations as determined by the marginal breakdown. Burnishing immediately before carving or as part of the condensation process seems to improve the carving characteristics of the amalgam. PMID- 8482783 TI - Latex glove reactions found in a dental school. AB - When a survey was distributed to students, faculty and staff of a dental school to determine the incidence of latex glove reactions, 15 percent reported adverse reactions to glove use. The most frequently reported symptom was dermatitis, followed by urticaria, sweating, conjunctivitis and rhinitis. PMID- 8482784 TI - Conservative color improvement for teeth with fluorosis-type stain. AB - This report describes use of carbamide peroxide bleaching gel to lighten the enamel of teeth after enamel microabrasion. PMID- 8482785 TI - Managing patients with Alzheimer's: the primary care role of dentists. AB - The primary care role of a dentist in the comprehensive care and management of a patient with Alzheimer's disease and the caregiver is described. As part of a geriatric assessment team, the dentist can contribute to a strategy addressing these patients' complex needs. PMID- 8482786 TI - Speaking out for dentistry. PMID- 8482787 TI - Temporomandibular disorders: a survey of dentists' knowledge and beliefs. AB - General dentists and specialists likely to treat TMD were surveyed to gain information on their understanding of TMD causes, diagnosis and treatment. While the role of psychophysiologic factors in the etiology of TMD has been widely acknowledged in the practicing community, there is still a high level of controversy about the pathophysiologic aspects of TMD and appropriate diagnoses and treatment. PMID- 8482788 TI - Single-step purification of F(ab')2 mu fragments of mouse monoclonal antibodies (immunoglobulins M) by hydrophobic interaction high-performance liquid chromatography using TSKgel ether-5PW. AB - A procedure is described for preparation and single-step purification of F(ab')2 fragments, herein designated as F(ab')2 mu' from mouse monoclonal antibodies of the IgM class. Hydrophobic interaction high-performance liquid chromatography (HPLC) using TSKgel Ether-5PW was well applicable to the purification. The IgM was digested with pepsin at the pepsin-to-IgM ratio of 1:200 (w/w) in 100 mM citrate buffer (pH 4.2) at 37 degrees C for 2 h. The digests were applied to the gel equilibrated with the buffer containing 1 M ammonium sulfate. F(ab')2 mu fragments were adsorbed onto the gel with the same buffer, and eluted by reducing the ammonium sulfate concentration to 0 M. The fraction containing F(ab')2 mu fragments was homogeneous (purity higher than 97%) by both sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel-filtration HPLC. The recovery of the antigen-binding site was 55-72%. The cycle time of the Ether-5PW HPLC was 40 min, and up to 98 mg F(ab')2 mu fragments. The molecular mass of F(ab')2 mu was estimated to be 144-146 kDa. In comparison with IgM, F(ab')2 mu lost entirely the complement C1q binding activity, and the sugar content was greatly reduced. The binding of IgM with non-specific proteins turned to be negligible, when IgM was converted to F(ab')2 mu, suggesting that the fragments are useful for immunological application. PMID- 8482789 TI - Real-time kinetic analysis of limited proteolysis by ion-exchange chromatography using compressed, non-porous agarose beads. AB - In biotechnology there is a great need for methods that can be used for kinetic studies of ongoing processes, such as limited proteolysis. Ion-exchange chromatography on a nonporous, compressed agarose matrix was used in the study presented in this paper to monitor papain cleavage of fungal cellulases. This non porous matrix allows completion of a chromatographic analysis, with baseline resolution, within 30-60 s. Utilizing this very fast chromatographic method one can monitor a proteolysis 'continuously' by repeated chromatographic analysis of the incubation mixture and, if desired, terminate it at the optimal moment. Fractions were also collected for identification by activity assays and analytical SDS-PAGE. PMID- 8482790 TI - The use of phenyl-Sepharose for the affinity purification of proteinases. AB - Phenyl-Sepharose is most often used as an adsorbent for hydrophobic interaction chromatography (HIC). We report on its effective use for the affinity purification of some extracellular thermostable proteinases from bacterial sources. Proteinases belonging to the serine, aspartate and metallo mechanistic classes were effectively retained by the media. Purification factors in the range of 2.9-60 and enzyme activity yields in excess of 88% were obtained. In some cases homogeneous enzyme was obtained from culture supernatants in a single step. A number of other proteinases from mammalian sources were also retained. The specificity of the enzyme/support interaction was studied. Proteinases complexed with peptide inhibitors (pepstatin and chymostatin) showed reduced binding to phenyl Sepharose indicating interaction with the active site cleft whereas modification with low molecular weight active site directed inactivators such as PMSF and DAN did not, indicating that binding may not be dependent on the catalytic site. Pepsinogen and the pro-enzyme form of the serine proteinase from the thermophilic Bacillus sp. strain Ak.1 were not retained by the media and could be resolved in an efficient manner from their active counterparts. PMID- 8482791 TI - Solute/solvent interaction corrections account for non-ideal freezing point depression. AB - A new highly accurate curve-fitting technique for looking at freezing-point depression data was proposed by Fullerton et al. (Biochem. Cell Biol., in press). The method involve plotting mass solvent to mass solute ratio (Mw/M(s)) vs. 1/delta T (i.e. the inverse change in freezing point). A measured molecular weight and a solute/solvent interaction parameter (called I value) are inferred from the resultant linear plot. The accuracy of the molecular weight method was first demonstrated with the monomers of ethylene glycol, glycerol, propanol, mannitol, glucose and sucrose to show a mean molecular weight error of 0.02% with root mean square (RMS) error 0.9%. The RMS error (0.9%) is our best estimate of the molecular weight measurement accuracy for the method applied to a monomer. This error is consistent with the experimental precision (approximately 1%) which implies no systematic error. Non-ideality is described with a single constant, I. Polyethylene glycol (PEG) polymers of increasing length (vendor designation 200 to 10,000 Da) were analyzed to show monotonically increasing non-ideality (I values of 0.12 to 3.67) with increasing molecular weight. The measured molecular weights agreed with the end-point titration value for the three smallest polymers (where the number of polymeric units was less than or equal to 7). The method underestimates the vendor molecular weights for longer polymers. This disagreement is assigned to segmental motion (internal entropy) of longer, more flexible, PEG molecules. PMID- 8482792 TI - The application of polystyrene waveguides to protein adsorption investigations. AB - The possibility of detecting peroxidase adsorption on the surface of a planar polystyrene waveguide has been studied using light of the wavelength adsorbed by the protein molecules. When a single-mode optical waveguide was employed, maximal protein sensitivity was obtained when the thickness of waveguide layer was about 1.5-times greater than the cutoff thickness. Adsorption kinetics of peroxidase on the surface of polystyrene was studied with single-mode waveguides. A minimum surface concentration of 0.1 mg/m2 was observed experimentally. PMID- 8482793 TI - Colorimetric assay to determine alcohol dehydrogenase activity. AB - A colorimetric assay has been developed to quantify alcohol dehydrogenase (ADH) activity. The advantage of this method over conventional spectrophotometric assays is that many samples can be processed at once in a 96-well plate, monitoring the absorbance at 590 nm with a microtiter reader. ADH inhibitors have been used to show the specificity of this method. The assay offers an easy and reliable test for monitoring routine measurements of ADH activity and could be a valuable tool for those involved in the biomedical research of alcoholism, as well as in gene expression methodology in which Drosophila Adh has been widely used as reporter gene in transfection assays. PMID- 8482794 TI - [Bacterial contamination of the anterior chamber and cataract surgery]. AB - The authors report the results of bacteriologic cultures of the anterior chamber aspirate after cataract surgery. The results were positive for 15 cases (24%). Nine cultures were positive for 27 eyes operated by phacoemulsification and 6 cultures were positive for 35 eyes operated by extracapsular cataract extraction. The origin of these organisms is the normal bacterial flora of the conjunctiva and the inoculum size is very small. The most commonly identified organisms are coagulase-negative staphylococcus and propionibacterium acnes. PMID- 8482795 TI - [Experimental use of liposomes carrying an antimetabolite (mitoxantrone) in filtering surgery]. AB - Fibroblast proliferation plays a prominent role in closure of conjunctival filtering blebs and extensive investigations are being carried out to optimize antiproliferative pharmacotherapy in the prevention of filtering bleb failure in glaucomatous eyes with a poor prognosis undergoing surgery. Intercalating agents such as doxorubicin or daunorubicin have been shown to decrease fibroblast proliferation in tissue cultures. A liposomal delivery system was developed in an attempt to obtain a sustained release effect and to minimize ocular side effects of mitoxantrone (Novantrone, MITX), an antineoplastic agent with intercalating properties. The objectives of this study were to demonstrate the entrapment stability of MITX in multilamellar vesicles (reaching about 60% and remaining at this level for 8-weeks storage) and to investigate its activity in vitro (cell cultures) and in vivo (sclerectomy ab externo in rabbits). We showed that entrapped MITX inhibited in a dose-dependent manner subconjunctival fibroblast proliferation (ID50: 0.03 micrograms/l at D3 in cultures) and prolonged the success of filtration surgery in rabbits (decrease of intraocular pressure of 8 mm Hg in treated eyes versus 1.8 mm Hg in control eyes; p < 0.01). These results indicate the potential of MITX-entrapped liposomes in the control of conjunctival scarring in filtering bleb surgery. PMID- 8482796 TI - [Corneal crystalline deposits in benign monoclonal gammopathies. Apropos of 3 cases]. AB - Unusual corneal crystalline opacities at the level of Bowman's membrane and superficial stroma were observed in 3 patients with benign monoclonal gammopathy. Corneal immunohistochemical examination showed that the deposits consisted of immunoglobulin crystals identical to the paraprotein found in the serum (with the same light chain: Kappa in 2 cases and Lambda in the third case). The factors and mechanisms governing intracorneal immunoglobulin deposition in the cornea are discussed. PMID- 8482797 TI - [Vitreoretinochoroidal heredo-dystrophy, microcornea, glaucoma and cataract]. AB - Vitreoretinochoroidopathy with microcornea, glaucoma and cataract must be considered to be a distinctively autosomal dominant affection. The authors present evidence in the form of 18 carriers of the same anomaly detected with a pedigree extending up to six generations. Microcornea and vitreoretinochoroidal dystrophy are the prime characteristics; hypertonia and cataract are induced complications. The syndrome may be attributed to a hereditary dysgenesis affecting the anterior part of the globe with trabecular and preequatorial corneal alterations. The dystrophy has a slow development as shown by the clinical and electroretinographic course. Present treatment only consists of controlling ocular hypertonia and cataract. PMID- 8482798 TI - [Complications of secondary implantation in patients with aphakia]. AB - We analyzed retrospectively the complications and visual results of 154 cases of secondary intraocular lens implantation. The follow-up ranged from 1 to 4 years (mean 2.8 years). Best corrected final post-operative visual acuity was better or the same as the best corrected preoperative vision in 95.5% of the eyes. Vision deteriorated in 7 eyes (4.5%): in 3 eyes because of cystoid macular edema, in 2 eyes because of retinal detachment, in 1 eye because of corneal decompensation and in 1 eye because of macular hole. The incidence of complications was 15.4%. We believe that, in carefully selected patients, secondary intraocular lens implantation is highly successful. PMID- 8482799 TI - [Optical power of the corneal epithelium]. AB - The refracting power of the corneal epithelium is relatively unknown. We measured the keratometric refracting power of the cornea in two series of 10 fresh bank eyes and on five cat eyes with and without epithelium. The readings were performed at the 2 and 3.6 mm optical zones with an automated keratometer and with a videokeratoscope (TMS-1). The mean change was +1.30 D (0.55-1.85 D) at the 2 mm optical zone and 0.85 D (0.2-1.6 D) at the 3.6 mm optical zone in the first series of 10 eyes. The optical power of the epithelium was most significant within the central cornea. By removing the epithelium there was an increase in corneal refracting power and a change in the power and axis of astigmatism. We discuss the consequences of these findings and how they might affect the outcome of photorefractive keratectomy or other similar keratorefractive procedures. PMID- 8482800 TI - [Simultaneous failure of trabeculectomy and sclerotomy using laser holmium: YAG]. AB - We present a case of a bilateral chronic open-angle glaucoma in a 74 year old woman, operated on the right eye by conventional trabeculectomy and the left eye by holmium laser ab externo sclerostomy. Both filtering blebs remained elevated and functional for 18 months. After this follow-up period, both blebs simultaneously collapsed and intra-ocular pressure rose again. This case shows that a late conjunctival scarring process, depending on a non surgical factor, may still be encountered after Holmium: YAG laser sclerostomy just as after standard trabeculectomy despite reduced conjunctival tissue trauma. PMID- 8482801 TI - [Bourneville's tuberous sclerosis]. AB - We present a case of tuberous sclerosis, classified as phacomatosis. The patient is a young woman admitted to hospital for a tumor in the right eye. The diagnosis of tuberous sclerosis was based on the presence of the various symptoms of this disease. The patient's ophthalmological symptoms were severe. Ophthalmologists must look for these symptoms in all subjects at risk, particularly in patients with epilepsy but also in the presence of cutaneous or visceral symptoms. PMID- 8482802 TI - [Epikeratoplasty for post-traumatic aphakia]. PMID- 8482803 TI - [Conjunctival cyst of the inferior fornix. Apropos of a case]. AB - Conjunctival cystic lesions are not uncommon and may arise anywhere in the conjunctiva, although the inferior fornix is one of the most frequent sites. We report the case of a 5 year-old-male black patient who underwent surgical excision of an unusually large conjunctival cyst of the inferior left fornix. The histopathological study showed that the cyst border was lined by a conjunctival epithelium, consistent with a conjunctival inclusion cyst. PMID- 8482804 TI - [Preventive treatment of herpetic keratitis with acyclovir tablets]. AB - Although several drugs are available to treat superficial herpes simplex keratitis, viral latency and recurrences represent clinical challenges that have been inadequately addressed by current topical antiviral agents. One hundred and ninety patients with previous herpes simplex keratitis were entered in an open study to evaluate the efficacy of the prophylactic therapy of recurrence with Acyclovir (200 mg) four times daily for 1 month to 24 months. Forty patients were treated because of frequently recurring herpetic keratitis; 36 were treated during a short period because of known risk factors; 23 were treated after ocular surgery which needed topical corticosteroid therapy in the postoperative period and 91 patients were treated after penetrating keratoplasty for herpetic keratitis. The results of this study indicate that oral Acyclovir significantly lowered the incidence of recurrences of herpetic keratitis in selected patients. PMID- 8482805 TI - [Vitrectomy and diabetic retinopathy]. PMID- 8482806 TI - [Ocular herpetic dendritic ulcer in a patient wearing soft contact lenses]. PMID- 8482807 TI - Effects of age and exercise training on size and composition of the rat left main coronary artery. AB - This study evaluated the effects of age and exercise training on the left main coronary artery (LMCA) in young (Y-5 months) and old (O-27.5 months) female Fischer 344 rats. Both age groups were divided into trained (T) and weight matched sedentary (S) control groups. Training consisted of 10 weeks of treadmill running progressing to a maximum workload of 15% grade, 1 hr/day, 5 d/wk at speeds of 36 and 15 m/min for the Y and O rats, respectively. Aging resulted in a 40% increase in left ventricle (LV) weight which was proportional to the increased body weight of the old animals. Exercise training produced a mild (approximately 10%) but significant left ventricular hypertrophy (LVH) in both trained groups. Cross-sectional area of the LMCA lumen and wall, wall thickness, and areas of collagen (C), elastin (E), and collagen-to-elastin ratio (C/E) of the LMCA wall were determined morphometrically in all four groups. A method for pinpointing the coronary ostium for use as a reference point was also developed. LMCA lumen area almost doubled (p < .001) across the measured age difference, but was unaffected by training. With aging, the increase in LMCA wall area bordered on significance (p < .053), while wall thickness, C area, and the C/E ratio were unchanged. Our results indicate that there is a disproportionate increase in the cross-sectional area of the rat LMCA with respect to LV mass changes with aging. This finding presumably reflects adaptation of this vessel to elevated resistances further downstream in the coronary circulation so that tissue perfusion can be maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482808 TI - Aging and the pharmacokinetics and metabolism of metoprolol enantiomers in the rat. AB - After i.v. administration of racemic metoprolol in the rat, the plasma concentrations of (R)- and (S)-metoprolol were comparable, and no differences in pharmacokinetic parameters between the two enantiomers were found. From the 3rd to the 12th month, comparable changes were seen for both enantiomers: there was an increase in the area under the plasma concentration-time curve (AUC) and a decrease in blood and plasma clearance. Half-life showed a significant prolongation, volume of distribution decreased between 3 and 12 months and increased between 12 and 24 months. After oral administration of the racemate, AUC and Cmax (maximum plasma concentration) were slightly higher, while oral clearance was slightly lower for (R)-metoprolol than for (S)-metoprolol. With aging, Cmax and AUC increased for both enantiomers, while oral clearance decreased. The change in oral clearance as a function of age is different between (S)- and (R)-metoprolol, and thus enantioselective. In vitro disappearance rate in 3-month-old rats was significantly higher for (S)-metoprolol than for (R) metoprolol, although the difference was small. With aging, the disappearance rates of both enantiomers increased significantly, but not enantioselectively. PMID- 8482809 TI - Identification of disease genes and somatic gene therapy: an overview and prospects for the aged. AB - Positional cloning strategies for identification of disease genes include genetic linkage analysis in disease families and identification of individuals in whom the disease is associated with a specific chromosomal anomaly. Once a genomic region likely to contain the disease gene has been identified, overlapping genomic clones are isolated and the candidate gene sought. Somatic gene therapy entails introduction of the cloned gene into somatic cells to either replace genetically defective functions or alter pathological disease processes. Transfer of the gene may be accomplished by either DNA- or viral-mediated methods into a variety of tissue targets. Once the success and reliability of ongoing gene therapy trials for various human diseases is established, it may then be considered in the prevention and treatment of chronic, disabling diseases such as Alzheimer's disease, Parkinson's disease, arthritis, and diabetes as well as intervention of immunosenescence, when the relevant genes have been cloned. Ethical considerations for gene therapy for aging are similar to those for gene therapy in general. In addition, the ethics of gene therapy for treating diseases versus intervention of the normal aging process must be considered. PMID- 8482810 TI - Comparison of the lateral diffusion constant of hepatocyte membrane proteins in two wild mouse strains of considerably different longevity: FRAP studies on liver smears. AB - The liver cells of male and female wild mice (Peromyscus leucopus and Mus musculus) have been studied in young, adult, and old age groups. Because P. leucopus displays a life expectancy of 7-8 years, the age groups of this strain were from 5.5 to 68 months. M. musculus survives only to about 2.5 years; therefore, the age groups of this strain ranged from 6 to 27 months. Protein lateral diffusion in hepatocyte membranes was measured by means of fluorescence recovery after photobleaching (FRAP) in liver smears. The peroxide-induced autofluorescence was utilized as a fluorescent label, which in H2O2 treated liver smears is caused by the oxidation of riboflavin bound uniformly to all proteins of the cell membrane. This way the average lateral diffusion constant (D) and the fractional recovery of those proteins can be measured. In both males and females of both strains D displayed a negative linear age correlation. Intraspecies sex differences were small and statistically insignificant. However, interspecies comparisons of males or females resulted in a strongly significant difference: although the intercept points of the regression lines describing D were identical in both strains (3.1 x 10(-10) cm2/sec), the decay of D with aging was about 2.5 times faster in the short-living M. musculus than in the long-living P. leucopus. By the end of life expectancy, both strains reached practically identical values (about 1.9 x 10(-10) cm2/sec). The results lend further support to the membrane hypothesis of aging. PMID- 8482811 TI - Uptake of serotonin into platelets of senile dementia of the Alzheimer type patients. AB - [3H]-serotonin uptake in platelets was studied in 26 patients with senile dementia of the Alzheimer type (SDAT), 29 age-matched normal elderly persons, and 21 young subjects. The results showed a significantly lower uptake of serotonin into platelets of SDAT patients than in those of elderly controls (p < .02). Uptake of serotonin into platelets of elderly normal subjects was significantly lower than in the young (p < .01). These differences were due to reduced Vmax, whereas Km was unchanged. Isolated plasma from SDAT patients did not affect the uptake of serotonin into platelets of elderly controls, and vice versa, i.e., plasma obtained from elderly controls did not affect serotonin uptake in SDAT patients. The results indicate that serotonin uptake into platelets is reduced in normal aging, and more so in SDAT. Moreover, the reduced uptake in SDAT is not caused by a plasma factor in SDAT patients. No correlation was found between serotonin uptake and degree of cognitive impairment in SDAT patients. PMID- 8482812 TI - Exercise increases average longevity of female rats despite increased food intake and no growth retardation. AB - In previous studies, male rats given access to voluntary running wheels showed improved survival. Because the male runners did not increase food intake, it was not clear whether their improvement in average longevity was due to decreased availability of energy for cell proliferation and growth or to another effect of exercise. In this study, female rats, which increase their food intake in response to wheel running, were used to determine whether exercise can increase longevity when availability of energy for cell proliferation and growth is not decreased. At age 5 mo, the female voluntary wheel runners were running 9173 +/- 3640 m/day (mean +/- SD); running distance declined to 965 +/- 483 m/d by age 34 mo. From 5 mo to 10 mo of age, the runners ate approximately 37% more than the sedentary rats. Thereafter, the runners ate approximately 20% more. The runners and sedentary rats attained similar peak body weights. However, the runners gained weight more rapidly, attaining steady state by 11 mo; the sedentary rats' weights did not plateau until approximately 15 mo. The runners had a significant prolongation of average longevity without an increase in maximal life span. The sedentary rats' average age at death was 924 +/- 155 days (mean +/- SD; range, 619-1263 d) compared to 1009 +/- 132 days (range, 693-1259 d) for the runners, p < .001. These results show that exercise improves average longevity of rats independent of decreased availability of energy for cell proliferation and growth. They also provide evidence that an increase in food intake is not harmful when balanced by an increase in energy expenditure. PMID- 8482813 TI - Morbidity and mortality in rural community-dwelling elderly with low total serum cholesterol. AB - BACKGROUND: Low serum cholesterol has been associated with morbidity and mortality in the elderly. This study compared the health, functional status, and two-year mortality rates of community-dwelling rural elderly with serum cholesterol < 150 mg/dl to age- and sex-matched controls with serum cholesterol 200-240 mg/dl. METHODS: Self-reported disease history, disability, health habits, and cognitive function data were collected at a health risk appraisal interview. A single blood sample was also collected and analyzed for total serum cholesterol at a central lab. RESULTS: Of the 3,874 participants, 109 (2.8%) had total cholesterol levels < 150 mg/dl. Seventy-five percent of the low cholesterol group were male compared to 44% in the main study population. The low cholesterol group had significantly greater smoking history, current cigarettes smoked, diabetes history, angina and COPD symptoms, and assistance needed for heavy and light work. Men in the low cholesterol group had significantly lower blood pressure. After two years, 14 (12.8%) of the low cholesterol group had died vs 16 (7.3%) in the control group. There was no relationship to specific causes of death and cholesterol level. CONCLUSION: A very low cholesterol level in older individuals should be evaluated carefully to determine whether it is due to genetic or life style factors such as diet or, more likely, is a marker of disease. PMID- 8482814 TI - Age and sleep modify finger temperature responses to facial cooling. AB - BACKGROUND: The increased incidence of hypothermia with age suggests that healthy 80-year-olds might show impaired responsivity to transient, localized thermal stimulation. Such a deficit might be particularly clear during sleep, when behavioral thermoregulation is less likely. METHODS: We examined finger temperature cooling in response to local cooling of the face--a response presumed to be centrally mediated. Nineteen healthy 80-year-olds (12 female) and twenty seven 20-year-olds (10 female) were exposed to repetitive 20-minute cooling and rewarming cycles across a night of sleep deprivation and a night of sleep occurring three nights later. We sought to determine whether thermal responsivity was altered by age and sleep, but by design avoided inducing core temperature hypothermia. RESULTS: In response to facial cooling during sleep deprivation, finger temperature decreased significantly more in the young than in old. This suggested relatively greater heat retention in the young. During non-REM sleep the thermal responsivity of both groups decreased and age-related differences were no longer present. Changes in core temperature induced by the stimulation were minimal. CONCLUSIONS: The results suggest that the capability of retaining heat via peripheral vasoconstriction while awake decreases with age. Despite this vulnerability, responsivity during non-REM sleep as well as average core temperature were comparable between age groups. PMID- 8482815 TI - Hospitals' motivations in establishing or closing geriatric evaluation management units: diffusion of a new patient-care technology in a changing health care environment. AB - BACKGROUND: Although Geriatric Evaluation Management Units (GEMs) are beneficial to patients, they are still new and their adoption by hospitals is unknown. This study describes the adoption of GEMs in a large sample of hospitals, and explores the reasons underlying hospitals' decisions to open (and sometimes close) an inpatient GEM. METHODS: A nationwide mail survey was conducted of 3,655 hospitals. The survey asked whether the hospital had an operating GEM, had a GEM that closed, had considered opening a GEM (but had not done so), or had not considered opening a GEM. The survey also requested specific information about operating or closed GEMs. Descriptive statistics, chi-square, t-tests, one-way analysis of variance, and Tukey's standardized range test for multiple comparison of means were used to analyze the responses. RESULTS: Among the 1,639 responding hospitals, 159 had established GEMs, 200 were evaluating the possibility of opening a GEM, and 1,263 had neither opened nor considered opening a GEM. Adopters were more likely to be large, urban, teaching hospitals. Evaluators were more optimistic than adopters about GEM's potential to meet financial goals. GEMs that closed tended to be located in hospitals experiencing budget deficits. Among adopters, space and nonphysician staffing were the most critical barriers to establishing a GEM whereas, for evaluators, identifying reimbursement sources and physician staffing were the greatest barriers. VA GEMs are smaller and initiated for different reasons than non-VA hospital GEMs. CONCLUSIONS: Despite their demonstrated usefulness, the adoption of GEMs has been limited. The reasons underlying decisions to adopt this new technology or close a GEM are often related to financial, not clinical concerns. PMID- 8482816 TI - Endurance exercise training reduces glucose-stimulated insulin levels in 60- to 70-year-old men and women. AB - BACKGROUND: Aging is frequently associated with development of insulin resistance and deterioration of glucose tolerance. Plasma glucose and insulin concentrations tend to be higher than in young people, even in those older individuals whose glucose tolerance is within the normal range. A sedentary life style could play a role in the development of insulin resistance and hyperinsulinemia with advancing age. METHODS: We evaluated the effect of 9 mo of vigorous endurance exercise training (approximately 80% of maximal heart rate) on the glucose-stimulated insulin response and glucose disposal rate, using the hyperglycemic clamp procedure, in 12 people aged 65 +/- 1 yr (mean +/- SE) with normal glucose tolerance. The post-training hyperglycemic clamps were performed approximately 16 h after a usual exercise session. RESULTS: VO2max increased approximately 23% in response to the exercise program. The plasma insulin concentration (I) during hyperglycemia (180 mg.dL-1) was significantly lower (mean 36 +/- 6 microU.mL-1 before vs 26 +/- 5 microU.mL-1 after; p < .05) after the exercise program. Insulin action was improved by the exercise, as the glucose disposal rate (M) during hyperglycemia was unchanged despite the blunted insulin response, resulting in an increase in the M/I ratio from 24 +/- 5 to 30 +/- 5 (p < .05), a value similar to the M/I ratio of 33 +/- 4 found in normally active young subjects. CONCLUSION: These results provide evidence that regular exercise is effective in reducing hyperinsulinemia and improving insulin action in 65-yr-olds to levels typical of young people. PMID- 8482817 TI - Nonsteroidal anti-inflammatory drugs and blood pressure in an elderly population. AB - BACKGROUND: Short-term clinical studies suggest that nonsteroidal anti inflammatory drugs (NSAIDs) may interfere with the effectiveness of antihypertensive therapies. We studied the joint effects of these two classes of drugs among subjects participating in the cross-sectional baseline interview from a population-based cohort study of community-dwelling elderly. METHODS: Blood pressure was recorded by interviewers using a standard sphygmomanometer after at least 5 minutes in the sitting position. Two recordings were made in rapid succession, using the first and fifth Korotkoff sounds. The second recording was used for this study. From respondents' medication container labels, interviewers recorded the name and dosage regimen of each medication used during the preceding two weeks. RESULTS: Persons on antihypertensive therapy taking NSAIDs had systolic blood pressures approximately 5 mmHg higher than those not taking NSAIDs, and were more likely to have systolic blood pressure above 140 mmHg (odds ratio = 2.19, 95% confidence interval 1.33, 3.61). These findings could not be explained by differences between NSAID users and nonusers in age, relative weight, or the type or dose of antihypertensive regimen. No significant effects of NSAIDs were seen for diastolic blood pressure or among persons not taking antihypertensive drugs. When analyses were restricted to non-indomethacin NSAID use, the findings were unchanged. CONCLUSION: These findings suggest that NSAID use may be an important community reason for loss of pharmacologic control of hypertension. PMID- 8482818 TI - Kinematics of recovery from a stumble. AB - BACKGROUND: Injuries most frequently related to accidents in elderly persons are falls during locomotion and stair ascent and descent. Although numerous risk factors have been related to falling behavior, effective strategies to predict and prevent falls have not evolved. The rationale underlying this study was that systematic experimental and analytical investigation of the effects of perturbations during locomotion and the subsequent requisites for recovery could lead to the development of clinically relevant evaluation(s) capable of identifying a predisposition to falling. The present study is the first biomechanical investigation of recovery from an anteriorly directed stumble. METHODS: Seven healthy, young males participated in this study. While the subjects walked along a walkway in the laboratory, stumbles were unexpectedly induced using a mechanical obstacle. Videotape records of these trials were analyzed and selected sagittal plane kinematics extracted. RESULTS: The perturbation caused an increase in the maximum trunk flexion angle from 4.3 degrees (control) to 18.3 degrees (p = .057), and this change was significantly associated with preperturbation walking velocity (p = .036). The maximum hip and knee flexion angles increased from 26 to 47 degrees (p = .039) and from 60 to 89 degrees (p = .009), respectively. The increases in maximum hip flexion velocity (79%) and maximum knee extension velocity (36%) were not significant. CONCLUSIONS: Identification of the principal elements of control during perturbed locomotion can contribute to understanding the relationship between specific age related performance deficits and some types of falling behavior. The results suggest that recovery from a stumble is dependent upon lower extremity muscular power and the ability to restore control of the flexing trunk. PMID- 8482819 TI - Personality development across the adult life span: subjective conceptions vs cross-sectional contrasts. AB - This research examined possible contributions of subjective conceptions about development to the study of long-term personality stability and change. Young, middle-aged, and old adult subjects rated 100 trait-descriptive adjectives with respect to perceived stability and change across seven decades of adulthood, their desirability, self-descriptiveness, and personal controllability. Subjective conceptions indicated growth during early and middle adulthood, followed by decline in old age. These conceptions were optimistic. They involved more growth than decline, and desirable traits were seen as more descriptive of self and more controllable than were undesirable traits. Older subjects were more optimistic about late-life development than were young or middle-aged subjects. In contrast, cross-sectional comparisons of self-descriptions indicated stability. Potential threats to the validity of both approaches are discussed, and it is concluded that the use of both measurement procedures will be beneficial for research on personality stability and change. PMID- 8482820 TI - Associations between early experiences with parents and well-being in old age. AB - This study explores the impact of early experiences with parents on health and well-being in old age. An interview survey was conducted with a representative sample of 267 elderly community residents in the age group 65-74. Standard measures for health, self-esteem, anxiety, depression, and loneliness were included as dependent variables. Quality of parenting was measured by means of a retrospective questionnaire focused on the care dimension of parental behavior. The foremost conclusion of this study is that early experiences with parents have an impact on the well-being of elderly persons. The effect is stronger among those older persons who lack a current attachment figure in the form of an affectionate partner; also, it is stronger for unattached older men than for unattached older women. PMID- 8482821 TI - Early parental loss and personal control in later life. AB - There has been a considerable amount of research on the impact of early parental loss on children and younger adults, but far fewer studies have examined whether the effects of this early traumatic event extend into late life as well. The purpose of this research was to see whether early parental loss is associated with diminished feelings of personal control among older adults who participated in a nationwide survey (N = 519). In the process of examining this relationship, a conceptual model was developed and tested to attempt to explain why early loss may exert this effect. This model tests the following theoretical sequence. First, it is hypothesized that early parental loss is associated with lower levels of educational attainment and that people with limited schooling are more likely to encounter financial problems in later life. Finally, this model predicts that greater financial strain is in turn associated with diminished feelings of personal control among older adults. Subsequent analyses of this model provide empirical support for these theoretical linkages. PMID- 8482822 TI - The role of social comparisons processes in the psychological adaptation of elderly adults. AB - Social comparison processes were investigated as mechanisms by which elderly women maintain or enhance their psychological well-being in the face of health related threats or loss. In Study 1, a measure of social comparisons was tested, and a preliminary model of the effects of health and social comparisons on depression was examined (N = 42). In Study 2, a separate sample of elderly women (N = 243) completed self-report measures concerning physical health, upward and downward social comparison processes, and positive and negative aspects of psychological adaptation. As predicted, worse physical health status was linked to more frequent social comparisons; however, more positive social comparisons were related to better mental health outcomes, even for women in poor health. In fact, the effects of social comparisons were strongest for women in the poorest health, resulting in psychological outcomes similar to women in good health. Thus, social comparisons appear to play a significant role in psychological well being in old age. The findings also point to the importance of distinguishing between frequency and consequences of social comparison processes. PMID- 8482823 TI - Improved foot position sense as a result of repetitions in older adults. AB - This research investigated whether acuity of perceived foot position changes as a result of repetitions in older and young adults. Subjects actively held four reference positions with one foot and matched these positions 12 times with the other foot. The data suggest that young adults performed the matching tasks with more overall accuracy and less variability than the older adults. Both young and older adults needed progressively less time to perceive an accurate match with repetitions. Repeated matching trials improved performance consistency in the older adults and resulted in less bias in both age groups. These results imply that adult aging affects the quality of the sensory signals conveying foot position at the ankle joint, but that repetitions make older adults more aware of proprioceptive feedback resulting in faster, more consistent, and more accurate performance. PMID- 8482824 TI - A comparative analysis of neuropsychological test performance of Spanish-speaking and English-speaking patients with Alzheimer's disease. AB - Because the diagnosis of dementia is highly dependent on the identification of neuropsychological deficits, there have been increasing concerns regarding cultural bias in tests designed to measure cognitive and intellectual function in English-speaking and Spanish-speaking adults. Despite their widespread clinical use, the effects of potential cultural bias on these measures among these two groups are largely unknown. We assembled a group of 76 females who received an NINCDS-ADRDA clinical diagnosis of Alzheimer's disease (AD). Half of these subjects were primary Spanish speakers, and the other half reported English as their primary language. All subjects were matched on chronological age and severity of memory impairment. Factors such as educational attainment and depression were entered into the analyses as covariates. The two groups were compared with respect to their performance on a battery of neuropsychological tests that are representative of what is typically used to diagnose the presence and severity of dementia. The finding that Spanish-speaking AD patients scored lower on specific neuropsychological measures is discussed in terms of inherent language biases and the possible lack of saliency of a number of these tests. The results obtained further suggest the need to modify certain neuropsychological indices so that they will better serve diverse ethnic and cultural groups. PMID- 8482825 TI - Age differences in mental rotation task performance: the influence of speed/accuracy tradeoffs. AB - Young and old subjects performed a mental rotation task with a within-subject instructional manipulation of speed/accuracy criteria. The three sets of instructions emphasized speed, accuracy, or both speed and accuracy equally. Both age groups changed reaction time (RT) in response to instructions, but there was no Age x Instruction interaction. Whereas young subjects showed decreases in accuracy with decreasing RT, older adults showed relatively stable levels of accuracy with decreasing RT, suggesting that young subjects were more willing to sacrifice accuracy for improvement in speed. Speed/accuracy operating characteristics for the two groups did not overlap, suggesting that age differences in response criteria cannot completely account for age differences in mental rotation performance. PMID- 8482826 TI - Time use of caregivers of impaired elders before and after institutionalization. AB - Time use was examined by means of time budgets obtained from 165 caregivers of older persons recruited from nursing home waiting lists and state nursing home assessment programs. "Yesterday interviews" were done at baseline (T1) and, again, an average of 5 months later when the elder had either entered a nursing home (n = 77) or was still awaiting entry (n = 88). Caregivers who provided more help (particularly instrumental assistance) to their elder were more likely to see that person placed in a nursing home at follow-up. More caregiving time was reported by those living with the elderly person and by nonworking and lower income caregivers; the elders being cared for by these groups were also more impaired. Less caregiving time (a total gain of 1 hour 47 minutes) was reported by caregivers following admission of the older person to the nursing home. The gained time was allocated to a significant degree to family interaction, recreation, and time outside the home. PMID- 8482827 TI - Classification of adult day care: a cluster analysis of services and activities. AB - Using data from a 1986 national census survey of 774 adult day care (ADC) centers, this study (a) determined whether distinct classes of ADC could be identified based on measures of program services and activities, and (b) delineated the distinguishing characteristics of such classes on other available measures of structure, process, and client population. A cluster analysis of 10 "process" measures of services and activities identified 6 classes of ADC centers: Alzheimer's Family Care, Rehabilitation, High Intensity Clinical/Social, Moderate Intensity Clinical/Social, General Purpose, and Low Scoring. Validity was examined by developing a set of expectations for pairs of classes on other available variables. Of 12 expectations, 11 were supported by the statistical tests. Finally, profiles of the 6 classes were developed to describe the classes on 30 other characteristics. The findings clarify the settings to which previous ADC studies are generalizable and indicate a need for effectiveness studies on special classes of ADC. PMID- 8482828 TI - Marriage and romantic involvement among aged African Americans. AB - This study examined the extent and structural correlates of marriage, romantic involvement, and preference for romantic involvement among older adults in a national sample of African Americans. Multivariate analyses indicated that gender, age, education, income, and urban residence were important predictors of marriage and romantic involvement. In particular, men and younger respondents were more likely than women and older respondents to be married, have a romantic involvement, or be desirous of a romantic involvement. The effects of the decreased probability of marriage for future cohorts of older African American women on their supportive networks, living arrangements, and income adequacy are discussed. PMID- 8482829 TI - Conjugal support: factor structure for older husbands and wives. AB - The purpose of this study was to investigate the factor structure of social support among older spouses. The sample consisted of 298 older marital dyads who participated in the Aging Couples Study. Confirmatory factor analysis techniques were used to examine conjugal support in a series of nested measurement models at the couple and individual levels. Two research questions were addressed: (a) the viability of conjugal support as a couple's construct, and (b) the dimensionality of social support within the marital dyad. Results showed that conjugal support was a husband/wife, rather than a couple, construct. Findings also showed that conjugal support was a multidimensional construct consisting of three factors: instrumental support, emotional support, and confiding. Moreover, husbands and wives perceived the dimensions of conjugal support differently. PMID- 8482830 TI - Patterns of nonresponse in a national survey of elderly Japanese. AB - Data from a nationwide sample of older adults in Japan were analyzed to determine patterns of unit nonresponse. Maximum likelihood logistic regression analyses identified age, sex, geographic region, and urbanicity as significant predictors of response status. The probability of nonresponse was higher for men, persons living in certain regions, and those in large urban areas. Age had a curvilinear relationship with response status; the probability of nonresponse decreased from age 60 to age 70, and then increased again with the highest rates at the oldest ages. When nonrespondents were disaggregated into three different groups based on reason for nonparticipation (i.e., refusals, not-at-homes, other reasons), variation in the results was found. For example, while men were more likely than women to refuse an interview or be absent from home during the survey period, they were no more likely to not participate for other reasons. Use of different response rate calculations and a substitution sampling procedure were not found to seriously affect study results. PMID- 8482831 TI - Changes in functional status and the risks of subsequent nursing home placement and death. AB - This research examined the effects of changes in functional status on the risks for subsequent nursing home placement and death. Using data on the 3,646 baseline self-respondents to the Longitudinal Study on Aging who were successfully reinterviewed at the first follow-up (1986) and who were not in a nursing home at that time, a two-stage analysis was conducted. First, the risks for nursing home placement and death between the 1986 and 1988 follow-ups were modeled based on a static set of baseline (1984) indicators. Measures of the change in functional health status between baseline and first follow-up were then introduced to determine whether such change had significant net effects and enhanced model fit. Substantial improvement in model fit was obtained for both outcomes. The risk of nursing home placement was associated with deterioration in advanced (i.e., cognitive) ADLs and lower body function. Deterioration in basic ADLs and lower body function was associated with the risk of dying. PMID- 8482832 TI - Analysis of IL-2, IL-4, and IFN-gamma-producing cells in situ during immune responses to protein antigens. AB - Immunohistochemistry has been used to define the patterns and kinetics of IL-2, IL-4, and IFN-gamma production at the sites of Ag exposure and in the lymphoid tissues of immunized mice, and to examine the anatomic relationships between cytokine-producing T cells and various APC or Ag-stimulated B cells. The earliest detectable cytokine response to administration of a protein Ag in adjuvant was the appearance of IFN-gamma-producing NK cells at the site of immunization by day 3. T lymphocytes producing IL-2, IL-4, and IFN-gamma were initially detected in draining lymph nodes and spleen within 7 days after immunization, and IL-2 producing cells were present at the immunization site several weeks later. Thus, T cell activation is initiated within lymphoid tissues, and these cells migrate back to depots of Ag. The IFN-gamma produced by NK cells early after immunization may regulate the phenotype of the subsequent Ag-specific T cell response. Using a hapten to which the antibody response is oligoclonal and dominated by a single idiotype, Ag-stimulated (idiotype-producing) B cells could also be detected by immunohistochemistry. These B cells were present in the same areas of lymphoid tissues as cytokine-producing T lymphocytes. Two-color staining showed that idiotype-producing B cells were in close proximity to both IL-2- and IL-4 producing T cells, suggesting that T cells producing either of these cytokines could provide helper function for the B cells. Finally, after subcutaneous immunization with adjuvant, IL-2+ T cells were found adjacent to F4/80+ macrophages, suggesting that macrophages function as important APC in this response. PMID- 8482833 TI - A mutant antigen-presenting cell defective in antigen presentation expresses class II MHC molecules with an altered conformation. AB - Ag presentation by APC to class II MHC-restricted T cells involves a sequence of events: 1) intracellular processing of protein Ag into immunogenic peptides, 2) specific binding of peptides to class II MHC molecules, and then 3) transport of the MHC-peptide complexes to the plasma membrane. The critical event in the activation of T cells by APC is the recognition of MHC-associated antigenic determinants by the TCR/CD3 complex. In this report we describe the isolation and characterization of a mutant APC with a defect in an intracellular process that results in its inability to form MHC-peptide complexes for recognition by T cells. The mutant APC cannot present many different protein Ag with both I-A and I-E molecules but is able to present processing-independent peptides. The functional defect in the mutant APC is not caused by either a decrease in expression or a structural mutation in class II MHC molecules. Further, there is no mutation in the invariant chain (li) and it displays a normal kinetics of association and dissociation from the class II MHC molecules during biosynthesis. Although the mutation is not in the genes encoding for the class II MHC molecules or li, the mutant APC expresses class II MHC molecules with distinct serological epitopes suggestive of an altered conformation. Pulse-chase experiments suggest that a conformational difference between I-Ad molecules of wild-type and mutant cells occurs after the class II molecules exit from the endoplasmic reticulum but while they are still associated with li. The mutant cell produces few compact (SDS-resistant) class II heterodimers. This mutant APC provides a tool for studying the cell biology of Ag processing and presentation. PMID- 8482834 TI - Phosphatidylserine enhances the ability of epidermal Langerhans cells to induce contact hypersensitivity. AB - Phosphatidylserine (PS) modulates several immune functions in vitro, including T cell activation, antibody and cytokine production, and macrophage growth. In the present work we studied the effects of PS on the induction of contact hypersensitivity (CH) in mice. BALB/c mice painted with PS (9.4-75 mg/kg) and with a sensitizing dose of DNFB or oxazolone on the same skin site exhibited a dose-dependent augmentation of CH reactions to either DNFB (> 60%) or oxazolone (> 35%), respectively. Bovine brain PS-enriched phospholipid mixture, lyso-PS, and dipalmitoyl-PS also induced similar enhanced CH responses, whereas phosphatidylglycerols had no effect. Increased CH was observed only when PS was applied from 2 days before to 12 h after DNFB. Immunization of naive syngeneic mice with skin grafts that were treated with PS and DNFB also led to enhanced (> 50%) CH responses. In addition, immunization by iv injection of epidermal cell suspensions enriched for Langerhans cells (LC) or of purified LC that were treated with PS (1-100 microM, 30 min, 37 degrees C), and then modified in vitro with DNBS (1 mg/ml, 30 min, 37 degrees C) led to increased (> 30-75%) CH responses in recipient syngeneic animals. Finally, adoptive transfer of DNFB immune lymph node cells obtained from mice that were treated with PS induced augmented CH responses in recipient animals. The results suggest that PS is capable of up-regulating the induction of CH in mice by stimulating the APC function of epidermal LC. PMID- 8482835 TI - Differential expression of IL-4 receptors in human T and B lymphocytes. AB - IL-4R have been described in unstimulated human T and B lymphocytes. However, a precise comparative study on the expression and regulation of IL-4R in isolated human T and B cell populations has not yet been fully assessed. We examined the mRNA levels and the cell membrane expression of IL-4R in freshly isolated T and B lymphocytes as well as in in vivo- and in vitro-stimulated cells. IL-4R protein expression and transcript levels were higher in tonsillar unstimulated B cells than in T cells. Splenic and peripheral blood B lymphocytes also expressed higher surface IL-4R in their membranes than T cells did. Large B lymphocytes from tonsils (in vivo-activated cells) obtained by Percoll gradient centrifugation displayed higher IL-4R levels than resting cells. On activation in vitro of T lymphocytes with IL-2 or PHA, slight increments on the IL-4R mRNA and protein levels were achieved. However, maximal levels of IL-4R expression were obtained on T cell incubation with IL-4 at a concentration of 100 U/ml. Similarly, the same concentration of this lymphokine up-regulated the surface IL-4R molecules and the IL-4R mRNA levels in purified B lymphocytes. Cross-linkage of surface Ig by insolubilized anti-IgM potentiated the effect of IL-4 in up-regulating IL-4R expression in B cells, probably by inducing outgrowth of IL-4R positive subpopulations. The B cell mitogen, Staphylococcus Aureus Cowan I, although inducing cell proliferation, was ineffective in promoting new receptor synthesis. Cell proliferation was not required for IL-4-dependent IL-4R up-regulation on both T and B lymphocytes. PMID- 8482836 TI - T cell receptor antagonism mediated by interaction between T cell receptor junctional residues and peptide antigen analogues. AB - A major objective of new rational immunosuppressive therapies is to be able to inhibit deleterious T cell responses in an Ag-specific manner. Recently, a novel approach to inducing Ag-specific nonresponsiveness in T cells, termed receptor or TCR antagonism, has been described. Several analogues of the influenza hemagglutinin (H3) peptide HA307-319 were shown to block recognition of the native HA307-319 peptide by a DR1-restricted T cell clone at concentrations 1,000 to 10,000-fold less than required to competitively inhibit HA307-319 binding to DR1. These Ag analogues that inhibited T cell recognition differed from the stimulatory antigenic peptide only at single positions. How such limited changes affect the ternary complex interactions of TCR, peptide, and DR remains unclear. In the present study, we have utilized two different DR5-restricted T cell clones that exhibit mutually exclusive specificities for HA peptides with or without substitutions at position 313 to investigate the molecular requirements for receptor antagonism. In this reciprocal model system, we show that a single peptide/DR complex can antagonize one T cell clone while stimulating another. A comparison of nucleotide sequences derived from the TCR of the T cell clones that were either antagonized or stimulated by the peptide analogue/DR5 complex indicated that the different responses of these T cells result from minor differences in the amino acid residues in junctional regions that most likely interact directly with position 313 of the peptide analogues. Our results suggest that TCR antagonism is an Ag-specific phenomenon in which T cells are inhibited by interactions involving TCR residues required for the recognition of conventional Ag and the altered residues in peptide analogues. PMID- 8482837 TI - Role of TNF-alpha in CD8+ cytotoxic T lymphocyte-mediated lysis. AB - The possibility that lymphokines such as TNF-alpha produced by CD8+ CTL are responsible for acute (short term) target cell damage induced by CTL has been debated for many years. However, the slow kinetics of TNF-induced target cell death stands in sharp contrast to the rapid target cell lysis mediated by CTL. We find that cloned CD8+ CTL activated through their TCR secrete TNF-alpha. On the other hand, our cloned CTL also have a membrane form of TNF-alpha, and they kill TNF-alpha-sensitive target cells not recognized through the TCR in a slow (18-h) lytic reaction using this surface-associated TNF-alpha. There is no secreted TNF alpha release during this interaction. Cyclosporin A and protein synthesis inhibitors block TNF-alpha secretion, but have no effect on slow lysis mediated by the CTL. On the other hand, TNF-alpha-resistant variants are greatly resistant to slow lysis, and antibodies to TNF-alpha strongly inhibit this slow lysis. Thus, although secreted TNF-alpha does not seem to be the mechanism behind slow lysis, some form of TNF-alpha, most likely the membrane-associated form, must be involved. Not only does surface TNF-alpha appear to be biologically active in these CTL, but its expression is enhanced severalfold upon activation of the CTL through the TCR. This may be important in vivo, where surface TNF-alpha could preserve the localized nature of cytolysis and endow a CTL with an additional, albeit slower, mechanism of cell lysis. Finally, we find that although activated CTL clearly use the membrane form of TNF-alpha in slow lysis, they appear not to use TNF-alpha, in any form, during acute lysis, even under conditions in which degranulation and perforin assembly are blocked. PMID- 8482838 TI - Role of CD8 in staphylococcal enterotoxin B-mediated lysis by cytotoxic T lymphocytes. AB - Recent evidence has suggested that recognition of superantigens such as the staphylococcal enterotoxins by CTL occurs independently of the accessory molecule CD8. These conclusions are based on the observation that antibodies to CD8 do not appear to be effective inhibitors of T cell lysis that is mediated by enterotoxin. This is in contrast to the well-known inhibitory effects of anti-CD8 antibodies on T cell activation by most peptide/class I complexes. In this study, we show that lysis of staphylococcus enterotoxin B (SEB)-bearing target cells by the mouse alloreactive CTL clone 2C is inhibited by anti-CD8 antibodies. SEB mediated lysis by a polyclonal population of mouse CTL was also inhibited by anti CD8 antibodies, but only under conditions where the SEB concentration is low. Inhibition occurs even when class I negative Daudi cells are used as targets. Thus, the observed inhibition does not appear to be due to the prevention of intercellular interactions between CD8 and class I molecules but is probably a consequence of preventing the intracellular association of CD8 and TCR. At the high ligand densities used in most previous studies, very few of the CD8/TCR complexes may be required for activation. Under these conditions, lysis may appear to be CD8 "independent" because 1) there are a sufficient number of preexisting CD8/TCR complexes for activation; or 2) prohibitively high concentrations of antibody would be needed to saturate unassociated CD8. PMID- 8482839 TI - Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells. AB - Signaling via the CD3/TCR complex induces programmed cell death (apoptosis) in immature thymocytes and transformed T lymphocytes (hybridomas or leukemic cells). Accumulating evidence indicates, however, that apoptosis can be triggered also in mature peripheral T cells. Here we show that a significant fraction of cells of a given IL-2-dependent TCR-alpha beta + clone or polyclonal short term line is killed when cultured for 20 h in the presence of PHA, anti-CD3 (OKT3), or anti TCR (BMA031) mAb. Apoptosis can be triggered by these stimuli in CD4+, CD8+, and CD4-CD8- (double-negative) TCR-alpha beta+ clones. Activation-driven cell death (as quantified by propidium iodide staining and FACS analysis) is associated with fragmentation of DNA into oligonucleosomal bands of approximately 200 bp. Although freshly isolated peripheral blood T cells are largely resistant to apoptosis, the sensitivity to anti-CD3/TCR mAb or PHA-triggered cell death gradually increases upon activation and IL-2-dependent culture of T cells, and reaches a plateau level after 15 to 20 days. These data indicate that stimuli that activate resting T cells initiate death by apoptosis in activated T cells. The implications of these results for the regulation of cellular immune responses and the establishment of peripheral tolerance will be discussed. PMID- 8482840 TI - Rat class III Fc gamma receptor isoforms differ in IgG subclass-binding specificity and fail to associate productively with rat CD3 zeta. AB - Several new rat class III Fc gamma R isoforms are described here, extending the genetic complexity of this receptor family and further distinguishing rat CD16 from mouse CD16, represented by only one receptor isoform, and human CD16, represented by only two isoforms. RNase protection assays reveal that three rat tumor cell lines--RBL-1 basophilic leukemia cells, RM-SV1 macrophages, and CRNK 16 NK cells--all coordinately express multiple and probably identical rtFc gamma RIII-related transcripts in similar relative proportions but at significantly different levels. These results indicate that no single isoform predominates in these cell types but that the overall level of rtFc gamma RIII-related transcripts is differentially regulated. Two of the rtFc gamma RIII isoforms found to have extensive amino acid sequence differences in their second extracellular (EC2) domains are shown to bind rat and mouse IgG subclasses differently. This result suggests that the receptor isoform diversity in this species may function as a mechanism for extending the IgG-binding capacity of rat leukocytes. Cloned cDNA for the rat CD3 zeta protein was also isolated in this study and its ability to augment surface expression of class III Fc gamma R was tested by rosetting of cDNA-transfected COS cells. Like the structurally homologous mouse CD3 zeta, rat CD3 zeta fails to promote surface expression of Fc gamma RIII, sharply contrasting the efficient receptor expression produced by human CD3 zeta. Variations in the transmembrane amino acid sequences correlate with the divergent capacities of these CD3 zeta molecules to augment receptor expression. The high levels of CD3 zeta message expressed in rat NK cells may indicate that other unidentified hetero-subunits are required for assembly of rat CD3 zeta into functional CD16 receptors. PMID- 8482841 TI - Ca2+ ionophore A23187-dependent stabilization of granulocyte-macrophage colony stimulating factor messenger RNA in murine thymoma EL-4 cells is mediated through two distinct regions in the 3'-untranslated region. AB - We analyze the role of the Ca2+ ionophore A23187 in the induction of GM-CSF mRNA expression in EL-4 thymoma cells. Northern analysis shows that A23187 increases the half-life of GM-CSF mRNA. To identify potential Ca2+ response elements in the GM-CSF mRNA, we produced stable transfectants containing pRSV-CAT (EL-4cat) or hybrid constructs in which most of the GM-CSF 3'-untranslated region (EL-4gm) or the adenosine-uridine boxes alone (EL-4au) were placed in a downstream position from the CAT coding region. A23187 induces a 4.4-fold increase in CAT activity in EL-4cat cells and a 210-fold and 48-fold increase in CAT activity in EL-4gm and EL-4au cells, respectively. Actinomycin D chase experiments in transfected cells demonstrate that A23187 increases the half-life of CAT mRNA from 15 min to 3 h in EL-4au cells and more than 3 h in EL-4gm cells, suggesting that the effect of Ca2+ is mediated predominantly by the adenosine-uridine boxes with a smaller contribution from upstream regions. To map these upstream regions, we transfected cells with constructs containing mutations of the 3'-untranslated region. With two of these mutations, corresponding to a region located about 160 bases upstream of the adenosine-uridine boxes, CAT activity was induced only 50-fold compared to 200-fold in EL-4gm cells. These data indicate that two regions within the GM-CSF 3'-untranslated region interact to modulate Ca2+ effects on GM-CSF mRNA half-life. PMID- 8482842 TI - A functional analysis of the antigenicity of streptokinase using monoclonal antibody mapping and recombinant streptokinase fragments. AB - Streptokinase (SK), a bacterial product of pathogenic Streptococcus species, is now widely used as an effective therapy for the treatment of heart attacks. Because naturally occurring antibody to SK is ubiquitous, serious allergic reactions to SK therapy are common. To begin to identify regions of the molecule that are important for the antigenicity of SK we performed studies using a panel of 51 hybridomas producing anti-SK antibodies, recombinant SK fragments, and assays of SK activity. Antibodies generated from mice hyperimmunized with wild type SK were shown to fall into six distinct complementation groups by competitive binding studies. Recombinant SK fragments were used to determine the peptide regions recognized by these complementation groups. Correlation of the effects of the mAb on SK function, with knowledge of their SK fragment-binding pattern, suggested regions of the SK molecule that are important for the construction and the catalytic function of the SK-plasminogen activator complex. PMID- 8482843 TI - Different effects of substitutions at residues 224 and 228 of MHC class I on the recognition of CD8. AB - Previous studies indicated that weak xenoresponse to HLA class I by mouse T cells is due to the inefficient interaction of mouse CD8 with the alpha 3 domain of HLA class I. The present study using chimeric H-2Kb molecules with recombinant alpha 3 domain between H-2Kb and HLA-B7 as well as single amino acid mutants of H-2Kb demonstrated that each substitution at residues 224 and 228 affects recognition of CD8-dependent mouse CTL clones. On the other hand, reactivity of IL-2 producing H-2Kb-specific T cell hybridoma transfected with mouse CD8 alpha was abrogated by substitution at residue 224 but not by that at residue 228. This indicates that the substitution at residue 228 affects recognition of CD8 dependent CTL but does not critically affect binding of CD8 to MHC class I molecules, although residue 224 abrogates binding of CD8. The model structure of the alpha 3 domain of H-2Kb suggests that the substitution at residue 224 induces conformational change of CD8 binding loop, whereas minimum structure change by the substitution at residue 228 is expected. It is therefore speculated that minimum structure change of CD8 binding loop by substitution at residue 228 may influence binding affinity of CD8, which abrogates recognition of CD8-dependent CTL but not IL-2 production of the CD8-dependent T cell hybridoma. PMID- 8482844 TI - Alteration of Leishmania donovani infection levels by selective impairment of macrophage signal transduction. AB - Leishmania donovani is an obligate intracellular protozoan which residues and multiples in macrophages. The molecular basis for this host-parasite interaction is poorly understood. Targeting a signal transduction pathway in the macrophage would allow this parasite to manipulate cellular gene expression, and this may aid in ensuring its survival. We demonstrate that in macrophages infected with L. donovani for 18 h, c-fos gene expression mediated through protein kinase A was unaffected under conditions where there was an impairment of protein kinase C (PKC)-mediated c-fos gene expression. This selective impairment of PKC-mediated c fos gene expression was substantially augmented in macrophages put in contact with L. donovani promastigotes or amastigotes for only 1 h. Treatment of macrophages with L. donovani-conditioned media was not sufficient to significantly impair signal transduction. These data revealed that L. donovani selectively impaired the transmission of information from the cell surface to the nucleus and that this effect is induced very soon after macrophage-parasite contact. The biologic significance of this altered signal transduction in the macrophage with respect to infection with L. donovani was then examined by treating macrophages with various protein kinase inhibitors prior to infection with amastigotes. Macrophages that were treated with PKC inhibitors demonstrated an increase in the initial uptake of the parasite and carried heavier infection levels than did controls. In contrast, treatment of macrophages with an inhibitor of calmodulin-dependent protein kinase (CaM-PK) did not show significant differences in the initial uptake of parasite, but prolonged impairment of CaM-PK resulted in a decrease in the level of macrophage infection. Further experiments revealed that promastigote proliferation was severely impaired by the CaM-PK inhibitor but not any of the other inhibitors. PMID- 8482845 TI - Increased protein kinase C activity in low density eosinophils. AB - Eosinophil heterogeneity is expressed in cell density, membrane receptors and function. It has been observed that increases in some functional activities correlate with decreased sedimentation density in human eosinophils. However, the cellular mechanisms to explain the up-regulation of eosinophil function have not been fully explored. Protein kinase C (PKC) is an important family of enzymes mediating signal transduction for a wide variety of functions in many different cell types. Changes in the activity of PKC could explain some of the observed differences in function. In these experiments, PKC activity of human granulocyte lysate supernatants was measured as the phosphatidyl serine-dependent transfer of 32P from [gamma-32P]ATP to a protein substrate under conditions of maximal stimulation; a measure of activatable PKC concentration. We observed that the activity present in eosinophils (87.2 +/- 8.4 pmol PO4 incorporated into histone per minute per 10(6) cells, n = 30) was not significantly different from that of neutrophils assayed under the same conditions (91.5 +/- 5.6 U, n = 31) but the percent of total activity that was phosphatidyl serine dependent was greater in eosinophils (97 +/- 1% vs 81 +/- 1% for neutrophils, p = 0.001). Blood eosinophils isolated from low density Percoll fractions had a higher activity (120 +/- 16 U) than that found in the higher density cells from the same subjects (81 +/- 19 U, n = 9, p = 0.011). When eosinophils recovered from bronchoalveolar lavage (BAL) fluid after segmental Ag challenges were assayed, the PKC activity of BAL eosinophils was similar to that of blood-derived eosinophils of equal density and low density BAL eosinophil PKC tended to be equal to or greater than higher density cells. The beta isozyme of PKC but not the alpha or gamma was detected in eosinophils by Western blotting with isozyme-specific mAb. These data indicate that eosinophil PKC activity is primarily caused by the beta-isozyme, is related to cell density in blood-derived cells, and may have a relationship to cell function. PMID- 8482846 TI - Modulation of lipopolysaccharide-induced cytokine gene expression in mouse bone marrow-derived macrophages by muramyl dipeptide. AB - Previous studies have shown that an i.v. injection of muramyl dipeptide (MDP) before a LPS challenge strongly potentiated serum TNF and IL-6 release in mice. Therefore the direct action of MDP was examined on TNF-producing cells, namely in macrophages stimulated or not by LPS. The level of TNF-alpha, IL-1 alpha, and IL 6 mRNA was determined in bone marrow-derived macrophages (BMM). A marked TNF alpha mRNA accumulation was found between 1 and 6 h after stimulation with MDP or LPS. LPS-induced IL-1 alpha mRNA transcript was delayed (3 h) than those after MDP induction (1 h). Conversely, kinetic induction of the IL-6 mRNA transcript was delayed in MDP-treated BMM as compared with LPS-stimulated cells. MDP pretreatment of BMM for 3 h not only enhanced the total level of LPS-induced TNF alpha, IL-1 alpha, and IL-6 mRNA (respectively 2.9-, 1.6-, and 2.4-fold increase), but it also delayed the kinetics of IL-1 alpha and IL-6 species accumulation. The enhancement induced by MDP pretreatment at the level of cytokine mRNA accumulation was correlated with an increase in LPS-induced TNF and IL-6 biologic activity production in supernatant fluids. In addition, in BMM from C3H/Hej mice MDP pretreatment enhanced the weak effect of LPS on TNF mRNA transcript accumulation and was required to produce LPS-induced TNF bioactivity. Our results suggest that MDP and LPS could act through distinct pathway(s) to induce cytokine gene expression. Moreover, the priming effect displayed by MDP could result in modulation of the LPS-induced cytokine gene expression at the transcriptional and/or post-transcriptional level. PMID- 8482847 TI - Uncoupling of early signal transduction events from effector function in human peripheral blood neutrophils in response to recombinant macrophage inflammatory proteins-1 alpha and -1 beta. AB - Macrophage inflammatory proteins-1 (MIP-1) alpha and beta are members of the C-C branch of the platelet factor 4 superfamily of cytokines, recently designated the "chemokine" superfamily. It has been suggested that the major cellular targets for the biologic activities of the C-C chemokines are the mononuclear leukocytes. However, the original designation of murine MIP-1 proteins as inflammatory mediators was based on suggestions that they activated neutrophil functions such as chemotaxis, the respiratory burst, and degranulation. In this study, we have evaluated the ability of human (Hu) MIP-1 alpha and beta to affect purified human neutrophil function. Although both rHuMIP-1 alpha and -1 beta stimulated significant calcium mobilization in human monocytes, only HuMIP-1 alpha exerted a detectable effect on neutrophils. HuMIP-1 alpha stimulated a small, dose dependent increase in intracellular calcium, which was accompanied by a simultaneous change in right-angle light scatter, the latter indicating induction of shape change. While the effect of HuMIP-1 alpha on calcium mobilization in neutrophils was small when compared with that elicited by IL-8 or Gro alpha, it had similar characteristics to that by other receptor-dependent neutrophil agonists in that it was dependent on pertussis toxin-sensitive G proteins and on both mobilization of calcium from intracellular sources as well as influx from the extracellular environment. In addition, stimulation of neutrophils with HuMIP 1 alpha led to desensitization to subsequent additions of HuMIP-1 alpha. The stimulatory effect of HuMIP-1 alpha on neutrophil calcium mobilization and shape change was not coupled to other standard measures of neutrophil effector function. For instance, neither HuMIP-1 alpha nor -1 beta had any detectable stimulatory effect on the Na+/H+ antiport, degranulation, actin polymerization, or chemotaxis. Moreover, although HuMIP-1 alpha binding could easily be measured on monocytes or monocytic cell lines, the number of sites were too few to characterize on neutrophils by the same technique. Taken together, these results show that neither HuMIP-1 alpha nor -1 beta stimulate significant neutrophil activation and support the concept that the biologic effects of members of the C C branch of the platelet factor 4 superfamily are not primarily directed toward neutrophils. PMID- 8482848 TI - MCP-1 expression by rat type II alveolar epithelial cells in primary culture. AB - Recruitment and activation of mononuclear phagocytes are potentially critical regulatory events for control of pulmonary inflammation. Located at the boundary between the alveolar airspace and the interstitium, alveolar epithelial cells are ideally situated to regulate the recruitment and activation of mononuclear phagocytes through the production of cytokines in response to inflammatory stimulation from the alveolar space. To test this hypothesis, we investigated the production of monocyte chemotactic polypeptide-1 (MCP-1), a protein that is chemotactic for and that activates monocytes, by rat type II alveolar epithelial cells in primary culture. Immunocytochemical staining using anti-murine JE, an antibody recognizing rat MCP-1, demonstrated cell-associated MCP-1 Ag throughout the monolayer. The intensity of staining was increased in response to IL-1 beta. When type II epithelial cells formed a tight monolayer on a filter support, there was polar secretion of MCP-1 Ag into the apical compartment by both control and IL-1-stimulated cells as measured by specific MCP-1 ELISA. Northern blot analysis revealed that IL-1 and TNF-alpha stimulated MCP-1 mRNA expression in a dose dependent manner, whereas dexamethasone blocked MCP-1 expression by cells stimulated with IL-1. In contrast to previous results using transformed epithelial cell lines, MCP-1 mRNA was induced in these primary cultures directly by stimulation with LPS. These data suggest that alveolar epithelial cells may have an important and previously unrecognized role in the initiation and maintenance of inflammatory processes in the lung by recruiting and activating circulating monocytes through the production of MCP-1. PMID- 8482849 TI - Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. AB - Monocytes/macrophages play a critical role in the pathogenesis of HIV infection, both as targets for virus replication and as sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, glycoprotein 120, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and IL-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that glycoprotein 120, similar to LPS, stimulates the secretion of endothelin-1, as well as TNF-alpha, from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction, we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene that is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex. PMID- 8482850 TI - Construction of a bispecific antibody reacting with the alpha- and beta-chains of the human IL-2 receptor. High affinity cross-linking and high anti-proliferative efficiency. AB - A bispecific antibody recognizing both the alpha- and beta-chains of the IL-2R was generated by sulfhydryl-directed chemical reassociation of monovalent Fab' fragments prepared from the anti-alpha mAb 33B3.1 (rat IgG2a) and from the anti beta mAb A41 (mouse IgG1). Whereas the 33B3.1/A41 bispecific mAb (bi-mAb) binds to isolated alpha- and beta-chains with low affinity (Kd = 4 nM), its binding to cells co-expressing the two chains shows both low and high affinity components. The high affinity-binding sites (Kd = 100 pM) most probably correspond to the cross-linking by the bi-mAb of alpha- and beta-chains, whereas the low affinity component corresponds to the excess of alpha-chains. High affinity binding of bi mAb on activated T cells is observed at 37 degrees C and not at 4 degrees C, suggesting that i) the two chains are dissociated at 4 degrees C in the absence of ligand and ii) the mechanism of bi-mAb catalyzed cross-linking of these two chains is temperature dependent. In contrast to parental 33B3.1 and A41 IgG, which recognize single positive (alpha + and beta +, respectively) and double positive alpha +/beta + cells with similar affinities, the 33B3.1/A41 bi-mAb is specific for activated alpha +/beta + cells with respect to its high affinity binding. In contrast to A41, which does not affect IL-2-induced proliferation of 4AS cells or anti-CD3-activated PBL, and to 33B3.1, which do inhibit proliferation but only partially and at high doses, the bi-mAb showed full blocking efficiencies at low concentrations (IC50 of 300 to 400pM) corresponding to the formation of high affinity alpha/bi-mAb/beta complexes. These half-maximal effects were observed at 10-fold lower concentrations than when using a combination of equimolar concentrations of parental 33B3.1 and A41 IgG. Because of their specificity and high blocking efficiencies, anti-alpha/anti-beta bi-mAb may constitute a better alternative for IL-2R-directed immunosuppression. PMID- 8482851 TI - Analysis of cytokine production by Mycobacterium-reactive T cells. Failure to explain Mycobacterium leprae-specific nonresponsiveness of peripheral blood T cells from lepromatous leprosy patients. AB - Recent analyses of antimycobacterial T cells clones from a small number of individuals indicate that mycobacteria preferentially induce Th cells that produce high levels of IFN-gamma and no or little IL-4 in Mycobacterium leprae resistant tuberculoid leprosy (TT) patients and healthy subjects, whereas in one study M. leprae-induced Ts clones from polar lepromatous leprosy (LL) patients showed a reciprocal cytokine secretion profile and mediated their suppressive activity via the release of high levels of IL-4. We have evaluated these findings in peripheral blood T cells from a larger panel of TT and LL patients as well as healthy individuals. Mycobacterium-reactive T cell lines generated from the PBMC of these individuals were tested for cytokine secretion and proliferative capacity in response to M. leprae, Mycobacterium tuberculosis, and various individual mycobacterial Ag. The lepromatous pole of the leprosy spectrum was additionally investigated by analyzing the cytokine-secretion profile of M. leprae-induced (suppressor) T cell clones as well as primary ex vivo PBMC. All T cell lines from healthy individuals and TT patients responding to M. leprae, M. tuberculosis, or individual Ag, produced high levels of IFN-gamma and TNF-alpha but little or no IL-4 and IL-6. At the lepromatous pole, T cell lines failed to proliferate upon stimulation with M. leprae but in some cases produced significant levels of IFN-gamma. No IL-4 or IL-6 secretion was observed in response to M. leprae. These lines displayed strong proliferation and Th1-like cytokine production upon stimulation with M. tuberculosis. Similarly, stimulation of primary PBMC from LL patients with M. leprae or M. tuberculosis resulted in the release of IFN-gamma but no detectable IL-4 production. Control tetanus toxoid-reactive T cell lines from the same individuals instead produced large amounts of IL-4 and low levels of IFN-gamma. The analysis of M. leprae-induced T cell clones, including those with known suppressive activity, revealed that all lepromatous T cell clones produced large amounts of IFN-gamma. Most of these clones released no or little IL-4, but some clones produced higher levels of IL-4 in addition to IFN-gamma. Most clones tested produced IL-10 as well. The suppressor activity of suppressor T cell clones could not be inhibited by a neutralizing anti-IL-4 antibody and only in one case by neutralizing anti-IL-10 antibody. Anti-IL-4 and anti-IL-10 could not overcome the M. leprae-specific unresponsiveness observed in primary PBMC from LL patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8482852 TI - A synthetic peptide analogue of a determinant of type II collagen prevents the onset of collagen-induced arthritis. AB - The immunization of genetically susceptible strains of mice with type II collagen (CII) elicits a collagen-induced arthritis that resembles rheumatoid arthritis. Our laboratory previously identified a region of CII, CII-245-270, that contains a T cell epitope that is prominent in the immune response to CII. Residues critical to the I-Aq-restricted presentation of this determinant have been characterized. To produce synthetic peptides with the potential of disrupting I Aq-restricted Ag presentation, synthetic analogue peptides were developed that contain site-directed substitutions in critical positions. One analogue peptide was found to be an efficient competitor for binding to I-Aq and to be capable of inhibiting T cell responses in vitro. When DBA/1 mice were coimmunized with CII and the analogue peptide, the incidence and severity of arthritis were greatly reduced, concordant with the humoral immune responses to CII. PMID- 8482853 TI - Induction of circulating IL-1 receptor antagonist by IFN treatment. AB - This study was undertaken to determine whether IFN induce IL-1 receptor antagonist (IL-1Ra), a specific inhibitor of IL-1. Plasma samples were obtained from healthy volunteers (n = 5) and patients with chronic hepatitis C (n = 5) treated with IFN-alpha, and from patients with renal cell carcinoma (n = 6) treated with IFN-gamma and assayed for IL-1Ra by a specific radioimmunoassay. Both types of IFN were administered subcutaneously. In vitro studies were carried out with PBMC from healthy volunteers. A single, low and nontoxic dose (1 x 10(6) U) of IFN-alpha induced circulating IL-1Ra, which reached peak levels within 12 h. This effect was dose-dependent and more pronounced with a higher dose (5 x 10(6) U). Peak IL-1Ra levels 12 h after 5 x 10(6) U IFN-alpha were 4.16 +/- 0.35 ng/ml in healthy volunteers and 5.7 +/- 0.73 ng/ml in patients with chronic hepatitis C (difference not significant). Thereafter levels declined but remained elevated for 24 h. IFN-gamma treatment led only to a modest increase of circulating IL-1Ra even at a dose of 400 micrograms; this dose, however, was associated with side effects similar to those seen after injection of 5 x 10(6) U IFN-alpha. PBMC stimulated with IFN-alpha or IFN-gamma produced IL-1Ra in vitro. The induction of IL-1Ra may contribute to the antiviral, anti-inflammatory, and antiproliferative effects of IFN. PMID- 8482854 TI - Surface-exposed conserved region of the streptococcal M protein induces antibodies cross-reactive with denatured forms of myosin. AB - Vaccines based on a highly conserved cell surface exposed C-repeat region of the group A streptococcal M protein molecule have been found to induce protection against mucosal challenge by homologous and heterologous streptococcal serotypes. Rabbit hyperimmune antisera were produced to four partially overlapping peptides of the C-repeat region of M6 protein. These were examined by both direct and competitive ELISA and by Western blotting for their reactivity against mammalian coiled coil proteins such as laminin, myosin, light meromyosin, heavy meromyosin, and cardiac tropomyosin, and to the denatured forms of some of these molecules. All sera reacted strongly with the recombinant M6 protein molecule. In addition, antibodies to three of the peptides displayed generally low levels of cross reactivity with at least one of the mammalian proteins, whereas antibodies to one peptide did not cross-react with any of the proteins tested. The observed reactivity was found to be directed predominantly against denatured forms of the mammalian molecules. For instance, the cleaved forms of myosin bound better to the cross-reactive antibodies than the intact molecule. Furthermore, heat denatured heavy meromyosin competed severalfold better in competitive ELISA than the non-heat-denatured "native" form. Our results demonstrate that M protein peptides corresponding to epitopes shared among rheumatic fever-associated strains of streptococci can lead to the production of low levels of antibodies reactive with mammalian coiled coil molecules. These antibodies are directed against the denatured forms of these molecules. PMID- 8482855 TI - Mapping human T cell epitopes in Leishmania gp63: identification of cross reactive and species-specific epitopes. PMID- 8482856 TI - Modulation of host response during infection with Trichinella pseudospiralis using immuno-stimulant drug. AB - Infection of the mouse with Trichinella pseudospiralis is accompanied by pronounced suppression of host inflammatory response. This study examines the effect of infection with this parasite on one major component of cell mediated immunity: delayed type hypersensitivity (DTH) reaction and the effect of administration of immunostimulant drug (Levamisole) on host response to T. pseudospiralis infection. Serum cortisol levels and the response of skin test to phytohaemagglutinin were used to construct the time table of drug regimen. Three groups were studied; group I (infected mice), group II (received levamisole on day 6 p.i.) and group II (received Levamisole on day 14 p.i.) Early administration of Levamisole restored DTH response to normal and histopathological examination of infected muscles revealed evident collagen deposition around the muscle larvae. PMID- 8482857 TI - Effect of various organic nutrients on the reproductive rates of bacterivorous hymnostomes in a freshwater canal, Shibin El-Koum, Menoufia, Egypt. AB - The effect of adding two different organic materials; wheat extract and bactopeptone was studied on some of the most abundant Bacterivorous Hymnostomes collected from freshwater canal in Shibin El-Koum, Menoufia. It was found that some of these ciliates prefer plant protein as wheat, others prefer animal protein as bactopeptone, someone have the ability to accommodate with both organic materials. A significant positive relationship between log doubling times and log cell volumes of these hymnostomes was confirmed. PMID- 8482858 TI - Counter immunoelectrophoresis, a modified technique for the identification of blood meals of sandflies collected from Qualyobia Governorate, Egypt. AB - Specificity and sensitivity are very important when investigating the blood meals of an insect vector, particularly those having different hosts. Several techniques are used for the identification of the blood meals. Counter immunoelectrophoresis is the technique of choice. The modification was to secure save of time and least amount of materials. In this paper, a modified technique of the counter immunoelectrophoresis (CIEP) was used for the identification of the blood meal of wild Phlebotomus papatasi collected from different sites in Qualyobia Governorate. Eight antisera were used. These were human, cat, dog, rat, sheep, goat, bovine and avian. The results showed that 99.52% of 832 female P. papatasi contained human blood, 0.12% (one female) contained only avian blood and 0.36% or three females each contained mixed blood of human together with dog blood (One), rat blood (one) or avian blood (one). P. papatasi is an anthropophilic insect, but in rare cases, it is zoophilic. PMID- 8482859 TI - Population dynamics of some synanthropic fly species in different habitats in Buraydah, Saudi Arabia. AB - The population dynamics of five synanthropic fly species, Chrysomyia rufifacies, Musca d. domestica Muscina stabulans F. Sarcophaga haemorrhoidalis, and Stomoxys calcitrans, were studied at three different habitats in Buraydah, Saudi Arabia. The chosen habitats were the slaughter house, the cattle market and the rubbish dumps. The number of flies caught per twenty sticky bands was taken monthly, for a whole year, as an index to the fly population at that habitat during that month. M. d. domestica was the most abundant fly species; it made up nearly 98%, 81% and 75% of the total synanthropic fly population at the rubbish dumps, the cattle market and the slaughter house, respectively. It reached its maximum abundance in May and minimum occurrence in January. House flies were collected throughout the year and survived conditions seemed to be unsuitable for other species. PMID- 8482860 TI - Scanning electron microscope observations on the digenean intestinal parasite Astiotrema reniferum (Plagiorchiidae). AB - The body surface of adult digenean intestinal parasite Astiotrema reinferum (Looss, 1898) Stossich, 1904 has been studied using scanning electron microscopy (SEM). The posterior region of the body forms a slender stalk terminating with two ventrolateral lobes. The lobes are armed with numerous large spine that are sharply pointed and orientated in all directions. There are regional variations in the distribution of spines all-over the body. The spines are abundant on the general body surface of the head region, the rim of the oral sucker, the inner lip of the ventral sucker and on the posterior ventrolateral lobes. No spines were observed on the genital pore and on the excretory opening. The sensory papillae found on both the oral and ventral suckers are arranged in a bilateral symmetrical patterns. They are dome shaped but some of them possess a short knob like process and others have no process. The papillae are more abundant on the oral sucker than on the ventral sucker. The possible functions of the spines and sensory papillae are discussed relative to their position. PMID- 8482861 TI - Delta virus versus HBsAg in chronic active hepatitis and their relation to clinical, laboratory, and morbidity findings in bilharzial and non-bilharzial patients. AB - This work was done to study the effect of delta virus and HBV infection, as two aetiological factors on clinical presentation, biochemical liver functions and prognosis of chronic active hepatitis (CAH) in schistosomiasis infected and non infected patients. 66.7% of the patients were carriers for HBsAg, among them 41.7% were infected with delta virus. It was evident that the clinical presentation of the patients with positive serological markers of HBV and HDV demonstrated advancing liver disease than in the other studied groups. Moreover, the biochemical liver profile was significantly affected when the triad of chronic HBV, delta virus and schistosomiasis infection was present. This could be related to the immunosuppression caused by schistosomal infection. Furthermore, mortality rate was significantly higher in schistosomiasis infected individuals. PMID- 8482862 TI - Studies on T. spiralis and T pseudospiralis larvae recovered from mice immunized with heterologous Trichinella antigen. AB - In this study, S3 antigen of T. spiralis and T. pseudospiralis was given to the heterologous infection in albino mice. The recovered larvae were studied as regards: their number, length and steroscan examination. It was found that vaccination of mice with T. spiralis (S3) antigen induced reduction in T. pseudospiralis larval count by 66.43% and significant reduction in length. Using T. pseudospiralis (S3) antigen reduction of 74.77% in T. spiralis larval count was detected as well as significant reduction in length. Scanning electron microscopic (SEM) examination revealed more or less similar finding in both species: loss of integrity of the cuticle, some of the larvae were attacked by granulocytes mainly eosinophils and few larvae appeared completely destructed with loss of normal architecture. A peculiar finding was noticed in case of T. pseudospiralis larvae in form of fine electron dense deposits giving the cuticular surface a motling appearance. PMID- 8482863 TI - Puffing activity after a heat shock in Musca domestica L. AB - Changes in puffing pattern after heat shock in Musca domestica were studied during the prepupal stage. Eight puffs which normally do not appear during development, were detected. One was found on chromosome X, one on chromosome III, two on chromosome IV and four on chromosome VI. Most of the observed puffs were large and had a complex structure characterized by visible granules. PMID- 8482864 TI - Some immunological aspects on human Schistosoma mansoni infection in Egypt. AB - Human Schistosomiasis mansoni is a chronic disease, which ranges from subclinical infection to huge hepatosplenomegaly. Reducing the risk of infection remains the aim of many control measures. So the present study was designed to evaluate the interaction between S. mansoni infection and immunological system of the host. The study included 3 groups of 50 adult males each. The first group was control group, the second group was early S. mansoni infection and third group was advanced schistosomiasis with hepatosplenomegaly. The results showed some changes in both humoral and cellular immune response during the course of infection. PMID- 8482865 TI - A new species of Eimeria (Apicomplexa) from Cordylus cataphractus (Sauria: Cordylidae), from South Africa. AB - Three armadillo girdled lizards, Cordylus cataphractus Boie, 1828, housed at the Dallas Zoo in Texas, USA but originally imported from Namaqualand, South Africa, were found to be passing oocysts of a previously undescribed species of eimerian. Oocysts of Eimeria murphyi sp. n. are cylindroidal, 44.1 x 21.3 (41.5-46.5 x 20.5 24) microns, with a shape index (length/width) of 2.07 (1.75-2.21). A micropyle and oocyst residuum are absent, but a polar granule is present. Sporocysts ellipsoidal, 13.5 x 10.2 (13-14.5 x 9.5-11) microns (N = 20), with a shape index of 1.32 (1.23-1.46). Each sporozoite possesses a single, posterior refractile body. This represents the first report of coccidia infecting a member of the saurian family Cordylidae. PMID- 8482866 TI - Helisoma duryi: its present range of distribution and implications with schistosomiasis snails in Egypt. AB - The range of distribution of Helisoma duryi, a potential competitor to schistosomiasis snail vectors in Egypt, was determined in the south of Nile Delta. Results show that H. duryi was found in the River Nile, Geziret El Kerateyeen banks, Damietta and Rosetta Branches, Tawfiky and Menoufy Canals and their branches and Bassoussiya, Bahadiya and Sheshaa canals and their branches. Helisoma was found in all categories of canals and drains co-existing in various degrees with other snail species including schistosomiasis vectors (Bulinus truncatus and Biomphalaria alexandrina). The population density of H. duryi and associated B. truncatus, B. alexandrina and Physa acuta were studied for one year in three channels. Statistical analysis of results show that Helisoma has a significantly negative correlation with schistosomiasis vectors in these channels. Helisoma population showed a major peak in the warmest months of the year (July-August) thus showing recovery in population after "Winter Closure" later than Bulinus, Biomphalaria and Physa. Helisoma proved to be free of any natural trematode infection. PMID- 8482867 TI - Studies on tissue cholinesterase in experimental trichinosis in albino rat. 2 effects of treatment with Mintezol and 5-fluorouracil-Endoxan. AB - The changes in cholinesterase (ChE) activity was studied in different tissues of normal and 60 days T. spiralis infected albino rats following treatment with Mintezol (5 mg/rat/day, for 5 days) and 5-fluorouracil-Endoxan (500 mg/rat/day- 100 mg/rat/day, for 5 days). In normal rats, administration of either Mintezol or 5-fluorouracil-Endoxan provoked a general decrease in the ChE activity of the various rat tissues. Treatment of 60 days T. spiralis infected rats with Mintezol increased markedly the ChE activity of the brain, liver, gastrocnemius muscle and serum. Meanwhile treatment with 5-fluorouracil-Endoxan decreased the enzyme activity in the selected rat tissues. It can be concluded that treatment with Mintezol and 5-fluorouracil-Endoxan in trichinellosis represents a certain danger. This danger results from general inhibition of ChE activity which may cause accumulation of acetylcholine. PMID- 8482868 TI - A survey of gregarines associated with Tenebrio molitor and Opatriodes vicinus in the central region of Saudi Arabia. AB - The present work recorded five species of septate gregarines in the intestine of two species of insects they were: Gregarina polymorpha (Hamm.), in the gut of Tenebrio molitor (L.), percentage of infection 100%, with a density of 2-6 and G. cuneata (Stein), in the gut of T. molitor (L.), percentage of infection 100% with a density of 15-17; Hirmocystis harpali (Watson), in the mid gut of Opatriodes vicinus (Fairmaire), percentage of infection 34%, with a density of 19-28 and Leidyana sp., in the mid gut of O. vicinus percentage of infection 17%, with a density of 2-11 and Spharorynchus chabaudi percentage of infection 33% with a density of 100-180 in an infected insect. Members of genus Gregarina are considered to be coccidian and malarial organisms, however, till now gregarines cause little or no damage to their hosts. PMID- 8482869 TI - Serum immunoglobulin and complement values in scabietic patients. AB - Immunity entails all the forces concerned with recognition, specific reaction and removal of foreign bodies after they again access into the body of the host. The immune system interacts with genetics and infectious agents as well as with metabolic, endocrine and environmental factors. The serum immunoglobulins (G.M.A. & E.) and complement (C3 and C4) were estimated in sixteen parasitologically proven patients with scabies. The causative agent was Sarcoptes scabiei. The results showed a high significant increase in the mean average of IgG., IgM. and in particular IgE pretreatment than in patients three months after treatment and in patients after treatment than in controls. On the other hand, there was a significant decrease in the mean average in the mean average of IgA after treatment was insignificant compared with controls. The C3 and C4 showed no significant changes in the mean average in the patients before or after treatment compared with controls. The changes in the IgG., IgM. and in particular IgE. may be specific reaction to the parasite or a non specific one to the dead parasite or its faeces or even to a secondary infection developed. On the other hand, the decrease in the IgA. may be due to the mite or its products which interfere with its synthesis. It is concluded that scabies is associated with a humoral immunological response against the mite infestation. PMID- 8482870 TI - A study on Phlebotomus species, the vectors of leishmaniasis in Gassim, Saudi Arabia. AB - A total 935 adult sandflies were collected and identified from Buraydah, Gassim region. Phlebotomus papatasi represented 79.6% of the total population whereas P. sergenti represented 20.4% throughout two successive years (October 1990- September 1992). Apart from May, female sandflies outnumbered the males in both species. The seasonal incidence of both P. papatasi and P. sergenti seemed to be highly affected by climatic factors prevailed in the study area. PMID- 8482871 TI - Entamoeba bovis Liebetanz 1905 recorded from large ruminants in Egypt. AB - Investigations carried out on trematode parasites affecting cattle and buffaloes in Ismailia Governorate revealed a degree of infection with Fasciola sp. attaining 6.95% among the former, and 16.16% among the latter. Concerning Paramphistomum sp. infection, it was 43.83% among cattle and 9% among buffaloes. During these studies, it appeared that cattle or buffaloes having no infection with Fasciola sp. or those being infected with Paramphistomum sp. only proved to harbour Entamoeba bovis trophozoites with a percentage of about 85% in cattle, and 80% among buffaloes. This protozoan parasite was also recovered from the gall bladders and bile ducts of slaughtered beef cattle that had no infection with liver flukes. The morphological picture of the fresh E. bovis trophozoite as well as its cyst were described, and the significance of such parasite on its host was discussed. PMID- 8482872 TI - Clinical and parasitological aspects on human scabies in Qualyobia Governorate, Egypt. AB - In the last decade, human scabies caused by Sarcoptes scabiei and other non human strains is one of the most common contagious parasitic disease. Over a period of one year (June 1991--May 1992), a total of 200 scabietic patients were diagnosed in the outpatients' clinic of Dermatology and Venereology, Benha University Hospitals. They were 120 females and 80 males (sex ratio = 1.5:1). Their ages ranged between three months up to 70 years old. Most of the patients were parasitologically positive (160 or 80%). The most common signs and symptoms were itching, skin burrows, scratch markings, papules and pustules. Regional lymphadenitis was sometimes present as well as fever in patients with secondary bacterial infection. The most affected sites were the abdomen (100%), followed by the buttocks (81.3%), the thigh (50%), legs (50%) and the arms and web spaces (62.5%). The male external genitalia was infested in 60% and the female breast was infested in 72.7%. The sex and site distribution of the infestations were attributed to the risk factor of exposure to infestation. The patients were successfully treated with 5% sulfur precipitate and 2-5% permethrin. The whole results were discussed on the light of the previous work. PMID- 8482873 TI - Isolation and concentration of microfilariae from peripheral blood of Wuchereria bancrofti infected patients by density gradient centrifugation. AB - A Ficoll-Hypaque gradient centrifugation technique was used for isolation and concentration of microfilariae from peripheral blood of 30 subjects with clinically and parasitologically diagnosed Wuchereria bancrofti infections. 86% of the microfilariae were found in the Ficoll-Hypaque layer. None were detected in the plasma, leucocyte layer or lower erythrocyte layer. 14% of microfilariae were identified on the top part of the erythrocyte layer. A 35 fold concentration and 88% quantitative recovery of parasites was achieved by conventional centrifugation of microfilariae-rich Ficoll-Hypaque layer. Following the centrifugation procedures, living motile microfilariae were separated. These results indicate that Ficoll-Hypaque centrifugation technique could be an effective method for the detection of low levels of microfilaraemia, and for obtaining relatively pure suspensions of living microfilariae for metabolic studies, production of antigen-rich excretory-secretory products and antigen analysis. PMID- 8482874 TI - Studies on the incidence and pathogenesis of Dicrocoelium dendriticum in slaughtered sheep in Riyadh abattoir, Saudi Arabia. AB - The incidence of Dicrocoelium dendriticum in slaughtered sheep both local and imported was carried out in Al Riyadh abattoir. A percentage of 28 was found among condemned livers. The highest rate of Dicrocoelium infection was among Naheemi sheep imported from Turkey. Recommendations to control this parasitic disease are necessary since it is a modern dangerous zoonotic parasite. PMID- 8482875 TI - The seasonal abundance of Gerbillus pyramidum and their flea ectoparasites in Al Arish, North Sinai Governorate, Egypt. AB - The seasonal abundance and the flea ectoparasites of Gerbillus pyramidum were studied. The results showed that the jerboa was more common in Summer (jerboa index 0.43) and least common in Winter (jerboa index 0.35). The overall male to female ratio was 4.2:1. The flea ectoparasites were more common in Autumn (flea index 10.5) and least common in Summer (flea index 6.8). The overall flea index was 8.75 and the majority of fleas (90.9%) was collected on male jerboa. The collected fleas in a descending order of abundance and flea index were: Xenopsylla cheopis (3.1), X. ramesis (2.7), Stenoponia tripectinata (1.4), Nosopsylla sinaiensis (0.9), Hopkinsipsylla occulta (0.6), and Pulex irritans. (0.01). PMID- 8482876 TI - Antifilarial IgM versus IgG antibody determination in the diagnosis of Wuchereria bancrofti infection in Egyptians. AB - Circulating antifilarial IgM and IgG antibodies were assessed by indirect ELISA in 184 serum specimens from 80 patients with clinically and parasitologically diagnosed filarial infections (20 with acute filariasis 40 with chronic filariasis & 20 asymptomatic microfilaraemic subjects), 64 individuals with other parasitic infections, 20 parasitologically-free subjects from filariasis endemic areas and 20 normal healthy controls. A soluble surface membrane extract from Dirofilaria immitis worms was used as the antigen. Using a single serum dilution of 1:128 and optical densities (OD) at 492 nm, the respective cut off values for IgM and IgG were found to be 0.24 and 0.22. All healthy non-endemic controls were seronegative by IgM and IgG ELISAs. The highest antifilarial IgM OD492 values were obtained in 20 patients with acute filariasis (95% sensitivity), while the highest antifilarial IgG OD492 values were observed n 40 patients with chronic filariaisis (97.5% sensitivity). Asymptomatic microfilaraemic subjects gave IgM and IgG OD492 values which were significantly lower than those of other forms of clinical disease and endemic control subjects. The antifilarial IgM and IgG respective sensitivities in asymptomatic subjects were 75% and 70%. Endemic controls had positive antifilarial IgM (65%) and IgG (75%) levels. Of 64 subjects with other parasites only one with Ancylostoma duodenale had positive IgM level (98.4% specificity); while 9 patients with nematodal infections mainly had false positive antifilarial IgG antibody levels (85.9% specificity). These results suggest that measuring circulating antifilarial IgM antibody level may have some diagnostic advantage over measuring IgG antibody level for the detection of active filarial infection and consequently better management of the disease. PMID- 8482877 TI - A study of autoimmunity in schistosomiasis. AB - Circulating auto-antibodies were estimated in sera of ten normal persons and fifty-four schistosomal patients classified into 3 groups: Group I 20 patients with early S. mansoni infection, Group II 20 patients with post schistosomal hepatic fibrosis and Group III 14 patients with post schistosomal glomerulonephritis. A significant high levels of auto antibodies (antinuclear antismooth muscle and antimitochondrial antibodies) were noticed in Groups II & III. Anti-ds DNA antibodies were significantly higher in Group III than in the other two groups. It was interesting to notice absence of rheumatoid factor in patients with schistosomal glomerulonephritis which may suggest that RF production may have a protective mechanism in patients with schistosomiasis against development of renal disease. PMID- 8482878 TI - Ecology of Biomphalaria alexandrina the snail vector of Schistosoma mansoni in Egypt. AB - The patterns of spreading and seasonal variation of population density of Biomphalaria alexandrina, the snail vector of Schistosoma mansoni in Egypt, in correlation with some environmental parameters were studied for 1988-1990 in four irrigation canals in Giza and Qalyoubiya Governorates. Results shown that the spreading patterns of snails along canals are changeable because of water current and irrigation activities. The snail population density showed two peaks, different in height, in April-May and November-December separated by two bottoms following the Winter Closure and during the hot summer season. The height of the peaks appears to be dependent on the extent of the "Winter Closure" and the prevailing water temperature. Two snail sampling tools, the dip-net and drag scoop, were used concurrently in this study. No considerable difference in sampling efficacy was recognized between these tools in the case of Biomphalaria. However, the dip-net appears to be more efficient in sampling other pulmonates while the drag scoop is more efficient in sampling prosobranchs. It is also realized that double sampling of 50% of sampling sites the next day should be satisfactory as a quality control system in snail population studies. PMID- 8482879 TI - New records of some of sarcophagid flies with distribution of all known flesh flies (Diptera:Sarcophagidae) of Saudi Arabia. AB - The Sarcophagidae (Flesh) of Saudi Arabia are reviewed based on collections of adult flies. Ten species of sarcophagid flies were recorded of which five are considered to be new record in Saudi Arabia. Checklist and information are given for each species concerning its geographical distributions and other observations. PMID- 8482880 TI - Effect of bacteriophage lysogeny on the efficacy of two bacterial larvicide formulations under field conditions. AB - Two types of man-made ditches were selected for carrying out this experiment; one polluted with nitrogenous matters (sewage water) and second filled with accumulated irrigated clear non-chlorinated water. No phages were detected in samples collected from both types of ditches. However, phage(s) specific to only B. sphaericus was (were) detected after spraying the two types with both B. thuringiensis H-14 and B. sphaericus commercial formulations. The detection of phage(s) was observed after 3 days post-spraying in the polluted ditch and after one week in the non-polluted one. This observation was explained by a possible transduction of naturally existed phage(s) on other spore forming bacteria to the sprayed B. sphaericus only, as its commercial formulation is based on spores which germinate to produce vegetative cell, while B. thuringiensis H-14 contains only the O-endotoxin as active ingredient, and also due to the increase of the number of bacteria in the sprayed ditches due to the recycling of B. sphaericus in the aquatic breeding places. PMID- 8482881 TI - Descriptions of new parasite species. PMID- 8482882 TI - Hydrocele in filarial and non filarial patients. Histopathological, histochemical and ultrastructural studies. AB - Twenty biopsied material of the testicular tissue were obtained from patients with unilateral hydrocele (eight due to lymphatic filariasis and twelve of idiopathic causes). Twenty biopsies lymphatic were also obtained from the normal unaffected testes and were used as control. The data obtained from histopathological, histochemical and ultrastructural studies revealed alternation in the testicular tissue with hydrocele than in the normal control testis. In the filarial hydrocele 37.5% of the cases showed thickening of the basement membrane and fibrosis with arrest of the spermatogenesis at the level of secondary spermatocytes. In addition, 12.5% showed thickening with interstitial fibrosis. Microfilariae were seen in hydrocele fluid of 3/8 cases (37.5%). In the idiopathic hydrocele 50% of the testicular tissue showed marked collagen deposits and testicular atrophy with fibrosis and thickening of basement membrane. The second 50% of cases showed variable degree of maturation arrests. Explanation for these variations in the pathological and anatomical pictures in both types of hydrocele is suggested. In the filariasis hydrocele it is due to the inflammatory response that may subside and recurrent. In the idiopathic hydrocele, it is due to the irreversible hypoxia caused by the continuous mechanical pressure due to huge amount of hydrocele fluid resulting in irreversible degenerative process with marked fibrosis. PMID- 8482883 TI - Assessment of serum copper and zinc levels in chronic Schistosoma mansoni patients with and without hepatic involvement before and after praziquantel therapy. AB - Estimation of serum copper and zinc was carried out on 40 Schistosoma mansoni patients with and without hepatosplenic involvement (group A and B respectively) before and after single oral dose of 40 mg praziquantel therapy as well as 20 normal controls (group C). Full clinical examination and assessment of liver function tests was done. HBsAg positive cases were excluded. The results showed a significant increase in the copper level in both groups (A and B) before treatment when compared to normal controls, and a significant reduction in zinc level only in group B. Following praziquantel therapy the copper level decreased with concomitant increase in the serum zinc level. PMID- 8482885 TI - The susceptibility of the Egyptian Phlebotomus papatasi to five insecticides. AB - Phlebotomus papatasi is the main vector of zoonotic cutaneous Leishmaniasis caused by L. major in nearly all the East Mediterranean Region. Generally speaking, control of any arthropod-borne disease should be directed against both the parasite and the vector. The present study was undertaken to establish a base line susceptibility levels of the Egyptian P. papatasi to five insecticides. These insecticides were: B H C and D D T (chlorinated hydrocarbon), permethrin (synthetic pyrethroides), malathion (Organophosphorus) and propoxur (carbamate). The results obtained revealed that the laboratory bred P. papatasi were more susceptible to the five insecticides than the wild caught ones. The insecticidal efficiency of the five insecticides based on LC50 was in the following descending order: propoxur, permethrin, BHC, DDT and malathion for laboratory bred flies and propoxur, permethrin, BHC, malathion then DDT for wild caught flies. The least LC50 was when using propoxur for both the wild caught flies (0.0014%) and laboratory bred ones (0.00043%). The least LT50 was when using propoxur for both the wild caught flies (4.8 seconds) and the laboratory bred flies (2.2 seconds). PMID- 8482884 TI - The effect of nifedipine [correction of nifidipine] and cimetidine on the haemodynamics of Egyptian bilharzial pulmonary hypertension. AB - The pathogenesis of bilharzial pulmonary hypertension differs from the hypoxic type of pulmonary hypertension. Nifedipine [corrected] a calcium channel blocker was tried as a treatment for lowering pulmonary artery pressure. Nifedipine [corrected] 20 mg sublingually was found to lower the pulmonary artery pressure but not to a statistically significant level. No significant changes before and after 200 mg cimetidine intravenous, were seen. PMID- 8482886 TI - Studies on tissue cholinesterase in experimental trichinosis in albino rat. 1. Effect of T. spiralis infection. AB - Adult male albino rats were orally infected with Trichinella spiralis (T. spiralis) larvae (400 larvae/rat). The cholinesterase (ChE) activity was then determined in the serum, brain, spinal cord, liver, stomach, intestine, heart, diaphragm and gastrocnemius muscle of the infected rats at different time intervals (15, 30, 45, 60 and 90 days) after infection. The enzyme activity was inhibited at all the time intervals in the brain, liver, heart and diaphragm while it increased progressively in the serum. In the spinal cord the ChE activity was inhibited at 15, 30 and 45 days postinfection but was markedly increased thereafter. In the intestine, stomach and gastrocnemius muscle the enzyme activity was generally increased. These alterations in ChE activity may be due to the stress effect due to the presence of the larvae in the tissues and/or the toxic effect or their metabolites. PMID- 8482887 TI - Development of Eimeria stiedae in a non-specific host. AB - Infection with E. stiedae was established in immunocompromised mice given dexamethasone for ten days prior to the infection and for two weeks later. The infection was similar to that of rabbits as regard the pathological and clinical picture. PMID- 8482888 TI - The management of spinal cord compression in patients with advanced malignancy. AB - We retrospectively evaluated the medical records of 17 hospice patients who developed spinal cord or cauda equina compression due to metastatic epidural tumor to ascertain the nature and outcome of the disorder in this setting. Epidural compression occurred following admission to the hospice in five cases and prior to admission in 12 cases. Six patients were ambulatory following treatment, and this favorable outcome occurred only in those who were ambulatory at diagnosis. In the group of patients who were paraplegic after treatment, problems related to pain, decubitus ulcers, and constipation were most challenging. This experience highlights the need for a more vigilant approach to back pain in patients at risk of epidural compression in the hospice setting. Further studies are necessary to establish the appropriate management of these patients. PMID- 8482889 TI - Pain in hospitalized patients with medical illnesses. AB - To evaluate the prevalence of pain in hospitalized patients with medical illness, we retrospectively reviewed the records of 313 consecutive admissions to the medical service of the Hennepin County Medical Center. Of the 224 eligible patients, 157 (70.1%) experienced nonprocedural pain on presentation or in the hospital, and pain was the chief complaint of 34.8%. In order of frequency, the most common types of pain were headache, cardiac pain, abdominal pain, noncardiac chest pain, joint pain, and hepatic pain. Female patients were more likely to have pain complaints, especially headache and joint pain. Patients with pain tended to be older, but this did not reach statistical significance. Among patients with pain, no quantitative assessments of pain intensity were documented in the medical record by any caregiver. This study underscores both the high prevalence of pain and the lack of pain assessment among patients hospitalized for acute medical illnesses. Adequate evaluation and management of pain should be considered as an important part of quality care. PMID- 8482890 TI - Patient-controlled analgesia for sickle-cell-related pain. AB - To delineate dose ranges, utilization patterns, and the frequency and types of problems encountered, we retrospectively reviewed the medical records of 46 patients with sickle hemoglobinopathies who used patient-controlled analgesia (PCA) a total of 92 times for the management of vasooclusive pain. Patients varied widely in the drug administered, use of basal infusion, individual dose, and total amount of drug received. On the day of heaviest use, the average maximum hourly dose was equivalent to 0.09 mg/kg of morphine. In this study, 11 patients and two families disliked PCA, one patient had respiratory compromise, and one patient tampered with the machine. Patient satisfaction with PCA probably reflects interactions among the psychosocial impact of chronic illness and chronic pain, individual psychological and temperamental factors, environmental contingencies, and the expectations and beliefs of the family and the health-care professionals. Based on this experience, recommendations can be proposed for the use of PCA in this condition. PMID- 8482891 TI - The Cancer Pain Role Model Program of the Wisconsin Cancer Pain Initiative. AB - The Cancer Pain Role Model Program was established in 1990 by the Wisconsin Cancer Pain Initiative to train physicians to be role models for appropriate pain management. Community and academic physicians along with their "clinical partners," a nurse or pharmacist, were recruited to attend a 1-day education conference that included lectures, small group workshops, and development of an action plan. A total of 44 physicians and 55 clinical partners have attended two conferences (1990 and 1991). Participants listed 199 activities on their action plans; postconference surveys have documented initiation of 212 projects aimed at educating others, improving clinical care, resource development, educating self, or research. The Cancer Pain Role Model Program appears to be a promising means of transferring cancer pain information, legitimizing cancer pain as an important treatment issue, and institutionalizing cancer pain management. PMID- 8482892 TI - Intrathecal infusional therapies for intractable pain: patient management guidelines. AB - This article focuses on appropriate patient selection for and management of patients selected for continuous spinal infusional opioid therapy. Patients with cancer-related pain who have undergone sequential strong opioid drug trials, who have intractable, unmanageable side effects, and who have undergone a successful spinal opioid efficacy trial are candidates for implantable spinal infusional therapy. Patients with noncancer-related chronic pain, who have failed all conventional syndrome-specific therapies before neuroablative surgical procedures, including sequential strong opioid drug trials, who have intractable, unmanageable side effects, and who have undergone successful spinal opioid efficacy trial are deemed candidates for implantable spinal infusional therapy. Patients with chronic noncancer-related pain and patient with cancer-related pain who have life expectancies greater than 3 mo all have implanted programmable infusion pumps. Patients with cancer-related pain who have life expectancies less than 3 mo have implanted permanent epidural catheters connected to external pump systems. Management guidelines for complications of therapy broadly categorized as surgical, mechanical, and pharmacologic are presented. PMID- 8482893 TI - Strontium-89 therapy in a patient with carcinoma of unknown origin and incurable pain from bone metastases. PMID- 8482894 TI - The use of opioid analgesics in an 11-year-old with a family history of drug abuse. PMID- 8482895 TI - Neonatal pain: a comprehensive survey of attitudes and practices. AB - We surveyed 352 physicians board certified in neonatal-perinatal medicine on their attitudes and practices in the area of pain and pain management in neonates and infants. In contrast to earlier surveys of this type, almost all respondents indicated that even the youngest and most premature infants are able to perceive pain, and most reported that they always advocated anesthesia during the intraoperative period. The use of analgesic agents in the postoperative period, however, was more variable. Respondents who indicated that neonates perceived less pain than adults reported seeing fewer signs of pain and using less analgesia in the postoperative period. They were also more likely to believe that analgesics are too dangerous to use in neonates and that physiologic factors such as incomplete myelination of the pain pathways and neural/physical immaturity (factors now known not to play a role) contribute to diminished pain sensitivity. Conversely, respondents who indicated that neonates do not perceive less pain than adults, the majority of respondents, reported seeing more signs of pain and using more medication in the postoperative period. These physicians also believed that the physiologic stress associated with pain can be more dangerous than the analgesics. We conclude that attitudes and reported practices have changed in the area of neonatal pain and pain management. Furthermore, our data indicate that these attitudes significantly predict reported postoperative medicating practices. PMID- 8482896 TI - [Distribution of occlusal stress on mandible, dentition and teeth]. PMID- 8482897 TI - [Development of a handy dental surveyor]. AB - A small portable surveyor, easy to use, was newly devised. The surveyor is essentially a parallelometer, an instrument used for determining the relative parallelism of two or more surfaces of the teeth or other parts of the dental cast. The characteristic structures of this instrument is as follows: The vertical standard is directly connected to the cast table with a universal joint, different from the others, and it can be tilted in any given degree to the table. The vertical sliding spindle can move freely parallel to the standard with the two horizontal arms, and it carries pencil leads of 0.9mm phi inside just as a mechanical pencil in structure. The accuracy of this surveyor is thought to be equal to that of the conventional ones in ordinary use. PMID- 8482898 TI - [Analysis of expression of p53 tumor suppressor gene in human oral squamous cell carcinoma]. AB - Expression of p53 tumor suppressor gene was examined in oral squamous cell carcinomas (OSCC), the precancerous lesions (leukoplakia) and cell lines established from OSCC, to investigate (1) whether or not all p53 mutations can be detected immunohistochemically and (2) when the alterations of the p53 gene and/or protein occur during the genesis of OSCC from leukoplakia. Over-expression was detected in 11 out of 16 cell lines with the anti-p53 monoclonal antibody PAb1801, although the remaining 5 cell lines have previously been reported to have mutations, thus suggesting that the immunohistochemical method has a limitation. To answer the second question, the ZA case was chosen as this case of OSCC with a point mutation at codon 279 had a history of leukoplakias which showed a malignant progression. The polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) method was employed to determine the presence of the mutation. Immunohistochemistry showed over-expression of the p53 protein in all 5 biopsy materials of leukoplakia, while the mutation was detected in 2 materials. In other 15 cases of leukoplakia, over-expression has a relation to epithelial dysplasia. These results indicate alterations of p53 gene and/or protein are observed not only in OSCC but also in leukoplakia and play an important role in the genesis of OSCC. PMID- 8482899 TI - [Isolation and characterization of oral treponemes]. AB - The oral treponemes were isolated on nine media and classified according to Anaerobe Laboratory Manual (1977). The four media, which were used with the plate in-bottle method, were Medium 10 (M10), M10 supplemented with 10% rumen fluid, M10 supplemented with 10% rabbit serum and cocarboxylate, and M10 added with rifampicin. The five media with the anaerobic glove box method were New Oral Spirochetes (NOS) medium, NOS medium added with rifampicin, alternated modified Oral Treponemes Isolation (aOTI) medium, and alternated M10 for anaerobic glove box. The isolation rate of the oral treponemes from 59 subgingival plaque samples of various forms of periodontal diseases was 85 percent. Ninety clinical isolates were subcultured and classified into six groups (I-VI) based on the carbohydrate fermentation and metabolic end products. Three saccaharolytic groups were further divided into nine subgroups by the fermentation patterns of sucrose, lactose, maltose and rhamnose. Two saccaharolytic subgroups were identified as Treponema socranskii, and two asaccharolytic groups were identified as "T. denticola" and "T. vincentii". However, the other subgroups and group could not be identified according to the characteristics of the presently recognized species. PMID- 8482900 TI - [Clinical study of masticatory movements in complete denture wearers--paths of masticatory movements and occlusal contacts]. AB - Bilateral balanced occlusion is believed to be one of the ideal types of occlusion for a complete denture since the occlusal contacts on the non-working side are concerned with the stability of the complete denture during mastication. In this study, the role of the occlusal contacts on the non-chewing side was investigated. The paths of masticatory movements were measured by sirognasograph and the occlusal contacts on the non-chewing side were measured by the 6-channel telemetry system. The results were follows; 1. The frequency of normal chewing pattern was observed to be higher in chewing on the habitual chewing side than in chewing on the non-habitual chewing side. 2. The average value in lateral deviations at the maximum opening point and maximum lateral closing point was larger in chewing on the habitual chewing side than in chewing on the non habitual chewing side. 3. Excursive closures were found in 36.0-71.1% among the total closures when chewing on the habitual chewing side and 4.9-20.9% on the non habitual chewing side. 4. The majorities of the excursive closures consisted of glidings from the lateral position to the centric position. 5. The width of the gliding in lateral excursion on the occlusal surface of the lower first molar was mostly 0.2-1.2mm. PMID- 8482901 TI - [Purification of bone morphogenetic protein and investigation of its effects on osteoblastic cell line UMR108]. AB - It is well known that the bone matrix contains proteins which can induce ectopic endochondral bone formation in vivo. One class of these proteins is the bone morphogenetic protein (BMP). In order to investigate the physiological function of the BMP, its purification was attempted from an extract of demineralized bone matrix and its actions on the osteoblastic cell line were investigated. To isolate the BMP, a demineralized bone matrix was extracted with 4M guanidine-HCl. A water-insoluble fraction (G-WI) was separated from the demineralized bone extract by dialysis against distilled water and centrifugation. The BMP was purified from G-WI by gel filtration on Sephacryl S-200 HR, cation exchange with Mono-S, heparin affinity column and finally by C1/8 reverse phase chromatography. Peptide sequence analysis revealed that the purified BMP fraction contained "BMP 3" reported by Wozney et al. (1988). In order to investigate its function, the BMP was applied to the rat osteogenic sarcoma cell line UMR108. The BMP inhibited the growth of the UMR108 cells and enhanced the alkaline phosphatase activity in a dose-responsive manner. PMID- 8482902 TI - [Osteopontin mRNA expression in remodeling alveolar bone incident to tooth movement--visualized by in situ hybridization]. AB - The purpose of this study was to investigate the osteopontin mRNA expression in the alveolar bone incident to the physiologic and experimental tooth movement. The upper jaws of female rats (7 weeks old) which were submitted to experimental molar tooth movement and control specimens were decalcified and sliced into paraffin sections. Osteopontin mRNA expression and tartrate-resistant acid phosphatase (TRACPase) activity were examined in the alveolar bone by use of in situ hybridization techniques and enzyme histochemistry, respectively. In the control specimens high levels of osteopontin mRNA expression was observed in the osteocytes and lining cells close to the osteoclasts which were detected by TRACPase staining in the distal areas of the tooth sockets. In the mesial tooth socket areas however, low levels of osteopontin mRNA expression was observed. In the experimental specimens high levels of osteopontin mRNA expression of both the osteoblasts and osteocytes was observed in the mesial areas of tooth sockets in response to the experimental tooth movement. These results indicated that osteopontin gene expression is related to the alveolar bone remodeling as far as the bone resorption incident to the physiologic tooth movement and that this expression level significantly increased in response to a certain mechanical stress incident to the experimental tooth movement. PMID- 8482903 TI - [Change in trigeminal mesencephalic neurons after teeth extraction in guinea pig]. AB - Trigeminal mesencephalic (Mes V) neurons innervating the periodontal mechanoreceptor (PMR) are known to play an important role in controlling the bite force and jaw-movements during mastication. After teeth loss, the PMR disappears due to loss of the periodontal membrane. The present work is a study on whether cell death is induced in the Mes V neurons in association with teeth loss. The upper and lower incisors were extracted on the right side in 5 guinea pigs (extraction group) and the other 5 guinea pigs were kept intact (control group). In the extraction group, the animals were kept alive for 58-119 days after teeth extraction. Serial coronal sections (50 microns thick) were made of the midbrain and pons and stained with cresyl violet. The Mes V neurons were counted on every other section. In the caudal half of the Mes V nucleus, where the neurons innervating the PMR are reported to be located, the number of neurons was less on the right side than on the left side (P < 0.01) in the extraction group, while there was no difference between the right and left sides in the control group. We conclude that teeth extraction can induce cell death in the Mes V neurons innervating the PMR and produce a significant change in the brainstem mechanisms controlling mastication. PMID- 8482904 TI - [Vascular endothelial cell proliferation suppressing factor produced by oral cancer]. PMID- 8482905 TI - [Right and left symmetry of the diameters of the crowns of the permanent anterior maxillary teeth and the relationship of their mutual compensation]. PMID- 8482906 TI - [Dental pulp irritation by various materials used to pretreat dentin]. PMID- 8482907 TI - [Oral cancer and tumor suppressive gene p53]. PMID- 8482908 TI - [Analysis of the path of the movement of the neural crest cells of the mammalian head region]. PMID- 8482909 TI - [Influence of various impression procedures for removable partial denture on displacement of soft mucosal tissue]. AB - In the impression-taking procedure for the distal extension removable partial denture, the pressure produced at the interface of the soft mucosal tissue and the impression material is the most important factor for the stability of the saddle under functional load. However, a review of the literature revealed little information about the displacement of the soft tissue caused by the impression pressure. In the present study, to investigate the influence of various impression procedures on the magnitude of the soft tissue displacement more precisely, a new three-dimensional deformation measurement system was devised. Compared to the previous studies, the greatest advantage of the system is that the hardened impression material can be surveyed directly without substituting a dental stone. It was found that, in the investigation using a partially edentulous simulated model, the amount of the subsidence in the soft tissue was increased as the thickness of the spacer of the impression tray was reduced or the seating speed of the tray was fast. Especially in the buccal area, a large amount of vertical displacement was present compared to the midridge and lingual area. Thus it was suggested that many factors are associated with the form of soft tissue under impression loading. PMID- 8482910 TI - [In vitro study on biocompatibility of zirconium and titanium]. AB - The purpose of this study is to evaluate the biocompatibility of zirconium compared with titanium by the in vitro study using human osteosarcoma cell line (HOS). Various characteristics of the HOS cells cultured on zirconium (99.9%) and titanium (99.9%) discs were investigated. On the colony formation of the HOS cells, there were no differences between the zirconium and titanium in colony size and number. Good proliferation of the HOS cells was observed on the zirconium as well as on the titanium. Morphological observation of the HOS cells by SEM revealed that the cells on the zirconium as well as on the titanium were flat and polygonal in shape with radial pseudopods. Collagen fibers and calcified substances were observed in the matrix of the HOS cells by TEM on the zirconium as well as on the titanium. The calcium of the HOS cell layer was stained well by Dahl's method. Analysis of the HOS cell layer by the Fourier transform infrared spectroscopy indicated that the HOS cells formed the same matrices including the apatite on the zirconium as on the titanium. Measurements of the zirconium and titanium elution into the human saliva indicated that the elution of zirconium was less than that of titanium. These results suggest that zirconium possesses as excellent biocompatibility as titanium. PMID- 8482911 TI - [Expression of glucocorticoid receptor gene during development of mouse embryos]. AB - Glucocorticoid, one of the steroid hormones, has been known to play important roles on homeostasis and development. To obtain information about the effects of glucocorticoid on the mouse embryonic development, temporal and spatial expression patterns of the glucocorticoid receptor (GR) gene were examined by the Northern hybridization and in situ hybridization techniques. Transcripts of the GR gene were found on embryonic day (ED) 10 by the Northern analysis. The amount of GR mRNA increased drastically on ED12 and was thereafter maintained at similar levels. On the other hand, obvious signals of GR gene expression were never detected until ED12 by in situ hybridization. On ED14 and afterwards, many organs, i.e. the pituitary gland, tongue, thymus, lung, liver and pre-cartilage, showed a high GR expression. These tissues were previously reported to be the target organs of glucocorticoid. The abrupt increase of GR gene transcripts in the embryonic tissues corresponded with the beginning of their maturation or function. These result suggest that the timing of the GR gene transcription becoming high in the embryonic tissues coincides with the onset of their terminal differentiation and function. PMID- 8482912 TI - [Influences of cusp inclination on stability and function of removable partial dentures]. AB - The influences of cusp inclination on the stability and the function of removable partial dentures were evaluated on 5 subjects with the maxillary unilateral free end saddle. An experimental removable partial denture was made with six pressure sensors fixed on to the basal surface. The artificial teeth were replaceable by attachment. Several metal maxillary canine risers were made to change the inclination of the lateral gliding movement. During lateral gliding, the canine risers and the artificial teeth were contacted with the opposing mandibular teeth simultaneously. The pressures exerted upon the supporting tissues and the mandibular movements were measured during mastication with each artificial teeth of different cusp inclination. The results were as follows: 1. The steeper cusp caused the reduction of the peak pressures as well as the total pressures in most measuring spots. 2. The time differences of the first and the peak pressure detection between 6 measuring spots extended as the cusp became steeper. 3. The mandibular movements were influenced by the cusp inclination especially in the subjects with tear-drop type masticatory strokes. 4. It was suggested that the moderate cusp of artificial teeth contributed to the denture stability in function. PMID- 8482913 TI - [Mechanical studies on dental magnetic attachments]. AB - The purpose of this study is to investigate the force distribution when using magnetic attachments in removable partial denture. The experimental magnetic attachments used in this study consisted of Nd-Fe-B magnets covered with permendur yokes and permendur keepers. The magnetic parts were attached to the experimental plate which was made of a titanium plate and an acrylic resin base, while the keepers were attached to the abutment teeth. The retentive force was measured by pulling the experimental plate vertically and diagonally with a tensile testing machine. In addition, the three-dimensional stress distribution of the abutment was analyzed by the finite element method when the magnetic attachment was removed. The results were as follows: 1. The maximum retentive force of the plate was influenced by the total of the attractive force, while the minimum force was by the number and arrangement of the attachments. 2. In almost all cases, the magnetic attachments worked most effectively when their attractive force was the same for each other. 3. When the pulling force was vertically applied to the abutment, the maximum stress arose in the alveolar bone around the root tip, and, when the force was laterally applied, the maximum stress arose on the axis of the 1/3 upper portion of the root. PMID- 8482914 TI - Cytokine priming of the respiratory burst in human eosinophils is Ca2+ independent and accompanied by induction of tyrosine kinase activity. AB - We report that pretreatment of human eosinophils with GM-CSF, IL-3, or IL-5 enhanced the respiratory burst induced by opsonized particles. In order to gain more insight into the intracellular mechanism(s) involved in cytokine priming, the role of [Ca2+]i and tyrosine kinases was studied. Optimal priming concentrations of GM-CSF, IL-3, and IL-5 did not induce a rise in [Ca2+]i, and Ca(2+)-depleted eosinophils ([Ca2+]i < 20 nM) were still primed after preincubation with these cytokines. GM-CSF, IL-3, and IL-5 induced phosphorylation of two proteins (102 and 122 kd) on tyrosine residues, as deduced from Western blot analysis with an antiphosphotyrosine monoclonal antibody (4G10). This cytokine-stimulated tyrosine phosphorylation was not inhibited under Ca(2+)-depleted conditions. In conclusion, this study demonstrates that GM-CSF, IL-3, and IL-5 priming of the opsonized particle-induced respiratory burst in human eosinophils is completely Ca2+ independent. Moreover the tyrosine phosphorylation of a 102-kd and a 122-kd protein is Ca2+ independent, suggesting that this event might be involved in cytokine priming. PMID- 8482915 TI - Laminin cleavage by activated human neutrophils yields proteolytic fragments with selective migratory properties. AB - We studied the interactions between human neutrophils, as well as the purified human neutrophil serine proteases elastase (HNE) and cathepsin G (HNCG), and laminin. Our results show that intact laminin and two proteolytic fragments generated by HNE bind to neutrophils and stimulate cell migration. Domain specific antilaminin monoclonal antibodies, rotary shadowing electron microscopy, and Western blotting mapped the two promigratory fragments on the laminin cross to the apical three-armed region and long arm, respectively. In contrast, a fragment derived from the terminal ends of short arms neither bound to neutrophils nor stimulated migration. When neutrophils embedded in a reconstituted basement membrane gel were activated with phorbol myristate acetate, several stable, proteolytic laminin fragments were released into supernatants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed that these fragments appeared identical to those generated after digestion of soluble laminin with HNE and HNCG. Furthermore, release of laminin fragments by embedded neutrophils was inhibited by diisopropyl fluorophosphate, and duplicated by incubating the basement membrane gel with purified HNE and HNCG. Our findings therefore suggest that neutrophils, through release of HNE and HNCG, are capable of digesting basement membrane laminin in vivo. In addition, the release of laminin fragments from damaged basement membranes may promote neutrophil migration and thereby accelerate inflammatory processes. PMID- 8482916 TI - Human pulmonary macrophages utilize prostaglandins and transforming growth factor beta 1 to suppress lymphocyte activation. AB - The ability to activate peripheral blood lymphocytes (PBLs) in vitro with interleukin-2 (IL-2) is suppressed by the presence of autologous human pulmonary alveolar macrophages (AMs). AMs suppress both IL-2-induced proliferation and the induction of lymphokine-activated killer cell (LAK) activity in a dose-dependent manner (79 +/- 6% suppression of LAK activity at a 0.25:1 AM/PBL ratio). Increasing the IL-2 concentration increased baseline LAK activity but did not prevent AM-mediated suppression. At least two different mechanisms of suppression were observed, one diffusible in nature and the other contact dependent. Indomethacin prevented the component of inhibition that diffused across porous polycarbonate membranes, indicating prostaglandins as the diffusible inhibitor. In contrast, indomethacin had no effect when added alone into conventional AM-PBL cocultures, but a combination of indomethacin and anti-transforming growth factor beta 1 (TGF-beta 1) antibody did prevent inhibition. This result suggests that TGF-beta 1 acts as an additional contact-dependent inhibitor. PBLs that were rendered unresponsive to IL-2 completely recovered their responsiveness within 4 days after removing AMs from the coculture. These features suggest that pulmonary macrophages have multiple mechanisms for locally suppressing IL-2 responses and lymphocyte activation. PMID- 8482917 TI - Affinity purification and subcellular localization of kinesin in human neutrophils. AB - Studies of granule-microtubule interactions in human neutrophils have suggested that mechanochemical ATPases such as kinesin or dynein may play a role in granule mobilization during neutrophil activation by inflammatory signals. In this study we show that proteins extracted from the surface of neutrophil granules, found previously to contain microtubule-dependent ATPase activity, caused microtubules polymerized from phosphocellulose-purified rat brain tubulin to move across glass slides. Antibodies were generated against peptides based on two regions of the amino acid sequence of Drosophila kinesin: the ATPase active site (amino acids 86 99) in the head of the kinesin heavy chain and the tail of the heavy chain (residues 913-933). These antibodies were found to recognize kinesin in rat brain extracts as well as kinesin-like polypeptides in extracts of human neutrophils. Furthermore, when used in immunoaffinity chromatography, these antibodies permitted the isolation of a protein from neutrophil granule extracts that was recognized by Drosophila kinesin antibodies. Subcellular localization by immunofluorescence microscopy showed this protein to be associated principally with the cytoplasmic granules of neutrophils. PMID- 8482918 TI - In vitro invasiveness of CTL clones and in vivo dissemination of CTL hybridomas. AB - Activated spleen T cells are invasive in hepatocyte and fibroblast cultures, and this property is dominantly expressed in T cell hybridomas. The invasive potential of the hybrids correlates with their capacity to disseminate in vivo. We have used this model to study the invasive and migratory properties of cytotoxic T lymphocytes (CTLs). Two murine CTL clones were highly invasive, independent of their state of activation. CTL hybridomas, derived from one of the clones, were similarly invasive. In vivo, CTL hybridoma cells disseminated to extravascular sites in the liver, kidneys, lungs, ovaria, tubae, uterus, and lymphoid, mesenchymal, and fat tissues. Within 7 to 14 days, 10(6) cells were lethal in 100% of mice. The adhesion molecules CD2, CD8, CD54, L-selectin, and CD49d (VLA-4 and LPAM-1 alpha-chain) were not expressed by all CTL hybridomas and therefore not indispensable for invasion in vitro and dissemination in vivo. In contrast, LFA-1 (CD11a/CD18), CD44, and VLA-6 (CD49f/CD29) were expressed on all hybrids. LFA-1 antibodies inhibited CTL hybridoma invasion in vitro, but antibodies inhibiting CD44-hyaluronate and VLA-6-laminin interaction had no effect. These results suggest that migration of cytotoxic T cells into noninflamed tissues is independent of their activation state and does not require L-selectin, LPAM-1, CD2, and VLA-4. PMID- 8482919 TI - Characterization of a human monocyte antigen, B148.4, regulated during cell differentiation and activation. AB - We analyzed the phenotypic changes associated with monocyte activation and differentiation using a newly developed monoclonal antibody (B148.4). Among peripheral blood leukocytes, the antigen recognized by this antibody is expressed on monocytes and granulocytes at high and low density, respectively. Antigen expression is lost during in vitro differentiation of monocytes and is absent on tissue macrophages, indicating that expression of this antigen is related to monocyte differentiation. Only 1 alpha,25-dihydroxyvitamin D3 and phorbol diesters, of several inducers tested, up-regulate B148.4 antigen expression on cells (monocytes and certain myeloid cell lines) that constitutively bear the antigen, without, however, allowing its maintenance during monocytic differentiation or inducing it on negative cells. By immunoprecipitation from B148.4+ U937 cells, the antigen is a complex of a major 116-kd and two minor 38- and 46-kd molecules. Analysis of eight different tissues reveals that the antigen is shared with endothelial cells. Biochemical characteristics, cellular distribution, and expression pattern on monocytes, myeloid cell lines, and AML cells upon culture with different stimuli indicate that B148.4 is a novel monocyte differentiation antigen. PMID- 8482920 TI - Diminished transcription of interleukin-8 by monocytes from preterm neonates. AB - Developmental delays, which impair antibacterial host defense, are present in the neutrophil system of human preterm neonates. We hypothesized that diminished production of interleukin-8 (IL-8), a neutrophil chemotactic peptide, might in part be responsible for these defects. To test this, monocytes from the blood of preterm neonates, term neonates, and adults were isolated immunologically by "negative panning" and subsequently stimulated with interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), or lipopolysaccharide (LPS), after which IL-8 levels in the supernatants were measured by ELISA. Total cellular RNA was extracted and IL-8 mRNA was assessed by Northern blotting and by competitive polymerase chain reaction (PCR) analyses. After stimulation with IL-1 alpha, IL-8 accumulation was lowest in supernatants of monocytes from preterm neonates, intermediate in supernatants of monocytes from term neonates and greatest from monocytes of adults. Similarly, when stimulated with TNF-alpha or LPS, monocytes from preterm neonates produced less IL-8 than cells from term neonates and adults. These differences in IL-8 concentrations paralleled differences in IL-8 mRNA expression. PMID- 8482921 TI - Functional alterations of human neutrophils by medium-chain triglyceride emulsions: evaluation of phagocytosis, bacterial killing, and oxidative activity. AB - Medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) emulsions currently used in nutritional therapy were evaluated for their in vitro effect on neutrophil oxidative metabolism, phagocytosis, and bacterial killing activities. Neutrophils from healthy adult male volunteers were assessed after blood incubation with commercially available fat emulsions containing LCT, MCT, or a mixture of 50% MCT and 50% LCT at a final triglyceride concentration of 20 mg/ml. It was observed that MCT-containing emulsions stimulated nitroblue tetrazolium (NBT) dye reduction by neutrophils as determined by a cytochemical NBT test performed directly on whole blood. This effect was dose dependent. However, after lipid removal by cell washing, the MCT-treated neutrophils showed decreased production of hydrogen peroxide (H2O2) and NBT reduction in response to bacterial lipopolysaccharide or phorbol myristate acetate stimuli as well as impaired phagocytosis and killing of Staphylococcus aureus. In contrast, the LCT emulsion did not alter any of the neutrophil functions evaluated. The present data suggest that MCTs elicit the oxidative metabolism of neutrophils, probably by phagocytosis of fat particles and, depending on the lipid concentration, this effect may not be reversible, leading to impairment of the cellular response to subsequent membrane stimuli. PMID- 8482922 TI - The mouse macrophage activation-associated marker protein, p71/73, is an inducible prostaglandin endoperoxide synthase (cyclooxygenase). AB - The inducible protein p71/73 marks the response of mouse macrophages to one of several stimuli (e.g., bacterial lipopolysaccharide or poly I:C) that trigger the expression of cytolytic activity when these cells have previously been primed for tumor cell killing by interferon-gamma (IFN-gamma). The results reported here identify this marker protein as the inducible prostaglandin endoperoxide synthase (PES), TIS10/PES-2. Identification was based on four findings: (1) p71/73, like the TIS10/PES-2 protein, was associated with cellular membranes; (2) the sequence of amino acids in the NH2 terminus of both p71 and p73 was 96% identical to the predicted NH2-terminal sequence of the TIS10/PES-2 protein; (3) a polyclonal antiserum raised against the COOH-terminal region of the TIS10/PES-2 gene product recognized p71/73 in immunoblots; and (4) dexamethasone, which blocks induction of TIS10/PES-2 expression, inhibited the induction of both p71/73 synthesis and tumoricidal activity in macrophage. Several regulatory roles for this protein in the activation process are possible. PMID- 8482923 TI - Transmembrane signaling pathways involved in phagocytosis and associated activation of NADPH oxidase mediated by Fc gamma Rs in human neutrophils. AB - We have previously shown that in neutrophils classical transmembrane signaling consisting of increased [Ca2+]i and hydrolysis of phospholipids was not essential for phagocytosis mediated by more than one receptor (yeast-IgG, yeast-C3b/bi, yeast-Con A). This work deals with the role of this transmembrane signaling in phagocytosis of erythrocyte (E) IgG, which is mediated only by receptors for IgG (Fc gamma Rs). The ingestion of E-IgG was associated with an increase in [Ca2+]i and production of inositol phosphates, phosphatidic acid, diacylglycerol, and arachidonic acid, via activation of phospholipases C, D and A2. Related to the same number of particles ingested, the respiratory burst and the transmembrane signaling during phagocytosis of E-IgG were much smaller than during phagocytosis of yeast-IgG. In Ca(2+)-depleted neutrophils, where the increase in [Ca2+]i and hydrolysis of phospholipids were lacking, the phagocytosis of E-IgG was depressed by about 60%; the respiratory burst was also depressed due to the decrease of ingestion and of stimulation of NADPH oxidase by residual phagocytosis. Pertussis toxin (PT) did not inhibit the phagocytosis of E-IgG but depressed by about 40% the stimulation of lipidic transmembrane signaling and the respiratory burst in normal neutrophils. In Ca(2+)-depleted neutrophils the toxin was without effect on ingestion and respiratory burst. Staurosporine did not inhibit the ingestion of E-IgG in normal and Ca(2+)-depleted neutrophils but depressed by 30-40% the respiratory burst in normal and not in Ca(2+)-depleted neutrophils. Genistein, an inhibitor of tyrosine kinase, did not inhibit the ingestion of E-IgG but depressed by 30-40% the respiratory burst both in normal and Ca(2+)-depleted neutrophils. These results demonstrate the following findings in human neutrophils. (1) Contrary to the phagocytosis mediated by more than one receptor (yeast-IgG, yeast-Con A, yeast-C3b/bi), the transmembrane signaling involving increase in [Ca2+]i and hydrolysis of phospholipids plays a role in the phagocytosis and respiratory burst mediated by Fc gamma Rs alone. Thus, different signal transduction pathways can be involved in phagocytosis and associated respiratory burst depending on the receptor or combination of receptors activated. (2) Fc gamma Rs alone promote phagocytosis with two signaling pathways independent of and dependent on [Ca2+]i changes and phospholipid hydrolysis and insensitive to PT, staurosporine, and genistein. (3) The signaling pathways promoting phagocytosis triggered by Fc gamma Rs alone are in some way, or at some step, different from those that activate the respiratory burst. PMID- 8482924 TI - C-reactive protein increases production of IL-1 alpha, IL-1 beta, and TNF-alpha, and expression of mRNA by human alveolar macrophages. AB - The concentration of C-reactive protein (CRP) increases in human plasma up to a thousandfold during inflammatory states. Because tissue macrophages have been shown to have receptors for CRP, the question arises of whether these cells may respond to increased local concentrations of CRP by producing cytokines capable of participating in the inflammatory response. Accordingly, we examined the capacity of alveolar macrophages--relatively accessible human macrophages--to produce interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in response to CRP. We found that production of IL-1 alpha, IL-1 beta, and TNF alpha, as measured by bioassay and immunoassay, increased in a dose-dependent manner after stimulation by CRP and that the levels of the respective mRNAs analyzed by Northern blot increased proportionally. These findings suggest that one of the functions of CRP may be to stimulate the production of IL-1 and TNF by macrophages at inflammatory sites where alterations of capillary permeability combined with an increased serum level lead to enhanced local concentrations of this acute-phase protein. PMID- 8482925 TI - Mast cell granules inhibit macrophage-mediated lysis of mastocytoma cells (P815) and nitric oxide production. AB - The effects of mast cell granules (MCGs) on macrophage-mediated lysis of P815 mastocytoma cells and nitric oxide (NO) production were studied. Murine peritoneal macrophages exhibited tumor cell killing and NO production only when activated with lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma). Coincubation of macrophages with MCGs during LPS activation dose-dependently inhibited macrophage-mediated tumor cell lysis. The MCG effect was not due to inactivation or removal of LPS by MCG. The inhibitory effect was also not due to histamine or serotonin present in the MCGs. The granules were not toxic to macrophages or P815 mastocytoma cells. The effect of MCGs on macrophage-mediated tumor cell killing was evident whether MCGs were added before or after a 4-h exposure of macrophages to LPS. However, the inhibitory effect was not seen if MCGs were added after macrophages had been exposed to LPS for 24 h. To assess whether MCGs could inhibit a non-LPS trigger, MCGs were tested on macrophages activated with IFN-gamma. In these experiments, MCGs dose-dependently inhibited macrophage-mediated tumor cell killing induced by IFN-gamma, LPS, or IFN-gamma plus LPS. Furthermore, in parallel experiments, MCGs significantly inhibited macrophage NO production induced by LPS, IFN-gamma, or IFN-gamma plus LPS. Pretreatment of MCGs with diisopropylfluorophosphate, a serine protease inhibitor, only partially abrogated the effects of MCGs. The results demonstrate that MCGs inhibit both LPS- and IFN-gamma-induced macrophage killing of P815 cells and the inhibition is associated with the decrease of NO production. PMID- 8482926 TI - Substrate-specific proteases (BLT-esterase) are localized predominantly in the natural killer cells of unprimed mice. AB - In leukocytes isolated from unprimed mice, the levels of extractable N alpha-Cbz Lys-thiobenzylesteresterase (BLT-esterase) closely correlated with the number of natural killer (NK) cells. The spleens of mice that exhibit severe combined immunodeficiency (SCID) contained much higher levels of this enzyme than other mouse strains. Treatments that resulted in a local accumulation of NK cells (as assessed by lytic activity) produced a concomitant increase in BLT-esterase activity. However, short-term in vitro treatment of spleen cells with interferon (IFN)-alpha/beta indicated that BLT-esterase levels correlated more closely with absolute numbers of NK cells than with their lytic capacity. There was a very good correlation between the numbers of cells bearing the NK phenotype (NK-1.1+) and BLT-esterase levels. Cells positively sorted using the NK-specific antibodies NK-1.1 and LGL-1 had high enzymatic activity. The BLT-esterase levels were high in both the NK-1.1+/LGL-1- and NK-1.1+/LGL-1+ subsets. Highly purified CD4+ and CD8+ T cells and sIg+ B cells demonstrated negligible enzyme, as did populations of cells highly enriched for macrophages or neutrophils. However, it should be stressed that the inbred mice used on this study have been maintained in a pathogen-free facility. It would be anticipated that mice maintained under less stringent conditions could exhibit appreciable levels of BLT-esterase activity in their T cells. Nonetheless, BLT-esterase is present at high levels in NK cells and cannot be regarded as a T cell-specific enzyme. PMID- 8482927 TI - Reconstitution of recombinant N-formyl chemotactic peptide receptor with G protein. AB - A recombinant human neutrophil N-formyl peptide receptor (rFPR) expressed in transfected mouse fibroblasts (TX2 cells) was analyzed for its ability to couple physically with the heterotrimeric G protein, Gi. Immunoprecipitation of photoaffinity-labeled rFPR and endogenous neutrophil formyl peptide receptor (nFPR) with an anti-FPR peptide antibody demonstrated that the receptors were identical in both size and extent of glycosylation. Coupling of rFPR with endogenous TX2 Gi was demonstrated by coimmunoprecipitation of the two proteins with an anti-Gi antibody. Moreover, rFPR was able to form a physical complex with purified Gi in a soluble reconstitution system. We observed similar affinities of rFPR and nFPR for Gi. This report provides the first direct evidence that rFPR associates physically with Gi and provides a foundation for analysis of the G protein coupling capacity of mutant rFPRs. PMID- 8482928 TI - LEEP. PMID- 8482929 TI - Clarithromycin vs penicillin. PMID- 8482930 TI - Clarithromycin vs penicillin. PMID- 8482931 TI - Bronc: a parable of compliance and patient care. PMID- 8482932 TI - Family secrets: a challenge for family physicians. PMID- 8482933 TI - Serum creatinine as an independent predictor of coronary heart disease mortality in normotensive survivors of myocardial infarction. POSCH Group. AB - BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality. PMID- 8482934 TI - Randomized placebo-controlled trials of antibiotics for acute bronchitis: a critical review of the literature. AB - BACKGROUND: Acute bronchitis is a common clinical problem that causes considerable morbidity and presents both diagnostic and treatment dilemmas for the physician. An evaluation of all published randomized controlled trials of antibiotics in the treatment of acute bronchitis was conducted to (1) quantitatively assess methodologic rigor, (2) determine if effectiveness of antimicrobial therapy is known, and (3) analyze strengths and weaknesses of randomized controlled trials in family practice settings. METHODS: A scoring system for the evaluation of randomized controlled trials was adapted for this study. Four raters, who were blinded to which journals published the studies and the type of antibiotic used in each study, assessed the six-randomized clinical trials for treatment of bronchitis identified through a literature search. The trials were rated according to criteria that measured internal validity. RESULTS: Scores for internal validity ranged from 65.5 to 102.5 points with a maximum possible score of 120 points (54.6% to 85.4%). The two trials with the highest scores assessed doxycycline and showed no benefit from use of this antibiotic. Single trials that studied erythromycin and trimethoprim-sulfamethoxazole showed improvement in outcome from use of these drugs; however, of the six trials, these two studies ranked fourth and fifth for internal validity. Low scores resulted from small sample size, possible contamination with other treatment measures, and poor assessment of subjects' compliance with antibiotic regimen. CONCLUSIONS: An evaluation of the current literature does not support antibiotic treatment for acute bronchitis. Further studies of this common illness are indicated. It is hoped that this critical review of randomized control trials will prove useful in the planning of future studies, in placing greater emphasis on methodologic rigor, and in giving greater consideration to the practical constraints of research in the family practice setting. PMID- 8482935 TI - Colposcopic accuracy in a residency training program: defining competency and proficiency. AB - BACKGROUND: The determination of proficiency in procedural skills has evoked keen interest, but meaningful guidelines are limited by the absence of pertinent clinical data. Colposcopic accuracy is defined as the clinical correlation between a colposcopic impression and a histologic report. The colposcopic accuracy of physicians in a university-based family practice residency colposcopy program was evaluated. METHODS: Demographic information, clinical findings, and laboratory results of patients evaluated by colposcopy were prospectively recorded. Colposcopic accuracy was calculated based on the agreement of the colposcopic impression with the histologic interpretation within one histologic grade. RESULTS: Colposcopic examinations were performed on 282 patients. Histologic evidence of premalignant cervical disease was identified in 115 patients as follows: mild dysplasia, 72; moderate dysplasia, 24; and severe dysplasia, 19. The colposcopic impression agreed within one histologic grade in 188 of 205 patients for a colposcopic accuracy rate of 91.7% (95% CI = 87.1% to 95.1%). CONCLUSIONS: Given an acceptable latitude of clinical correlation between the colposcopic impression and histologic interpretation, the colposcopic accuracy of family physicians compared favorably with that reported by other colposcopists. The more common colposcopic errors were overestimation of low grade disease and underestimation of high-grade disease. Colposcopic accuracy at an essential minimal proficiency level of 80% should form the basis for assessing specialized perceptual ability and therefore determining colposcopic competency. PMID- 8482936 TI - Health care needs of Appalachian trail hikers. AB - BACKGROUND: With a growing interest and participation in hiking, predictions indicate that over 45 million Americans will participate in backpacking and day hiking in 1993. There has been very little assessment of the health care needs of this group. The purpose of this study was to assess the health care needs of Appalachian Trail backpackers. METHODS: Backpackers who completed hiking the Appalachian Trail in 1987 or 1988 received a 3-page survey questionnaire. The survey contained questions to elicit demographic information, general health characteristics, and health care experiences during the hike. Information about injuries, medications carried and used during the backpacking activities, health care needs, and trail time lost because of health problems was also requested. RESULTS: Injuries and illnesses were reported by 82% of the respondents, incurring an average loss of 4.7 days of hiking. Musculoskeletal complaints, traumatic injuries, and gastrointestinal complaints were most often reported. The severity of these problems was such that medical attention was sought in 25% of these events. CONCLUSIONS: Hikers need to anticipate that musculoskeletal, gastrointestinal, and skin problems may occur during hiking. It is prudent to carry medications such as analgesics in the form of aspirin or other nonsteroidal anti-inflammatory agents, topical antibiotics, and bandages. Methods to purify water need to be used regularly, and adequate preparation of food needs to be a priority. PMID- 8482937 TI - An evaluation of two compact analyzers used for lipid analysis. AB - BACKGROUND: A number of relatively inexpensive compact analyzers are available for use in physician offices and outpatient clinics to measure total cholesterol and, more recently, high-density lipoprotein (HDL) cholesterol and triglycerides. This study was designed to document the analytical performance of two of them, the Abbott Vision and the Kodak Ektachem DT60, for assays of total cholesterol, HDL cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol. METHODS: Lipid profiles were measured from venous blood samples of 70 subjects with each test device, and results were compared with those from a laboratory standardized to the Centers for Disease Control. Coefficient of variation (CV) of multiple measurements from three pools of human serum (ie, precision), mean percent difference between device and standard laboratory results (ie, accuracy or bias), and 95% tolerance intervals (total error) were determined. The correct classification of patients into risk categories with device results was compared with the standardized laboratory results. RESULTS: The average CVs for total cholesterol, triglycerides, and HDL cholesterol with the Vision analyzer were 3.6%, 4.4%, and 10.5%, respectively, and with the DT60, 5.0%, 4.1%, and 6.8%, respectively. The average percent biases for the same analytes with the Vision analyzer were 0.2%, 4.0%, and -2.3%, respectively, and with the DT60, -2.1%, 12.1%, and 0.1%, respectively. Total error assessments indicated that total and HDL cholesterol measurements in individual patients met the guidelines of the National Cholesterol Education Program with both devices, but that triglycerides and LDL cholesterol measurements did not. Classification of subjects into risk groups based on total or LDL cholesterol gave clinically satisfactory results with either device. CONCLUSIONS: More precise measurement technology for LDL cholesterol is needed. Physicians and others who rely on compact analyzer results for diagnosis and treatment decisions should consider the degree of inaccuracy and imprecision in these values. PMID- 8482938 TI - Attitudes of Florida family practice residents concerning obstetrics. AB - BACKGROUND: The cost of liability insurance for obstetrical care and the fear of eventual litigation are reasons commonly cited by family physicians for not delivering babies. METHODS: Separate surveys were mailed to residency directors and third-year residents in Florida family practice residency programs to determine the attitude and practice plans of recently trained family physicians in regard to obstetrics. RESULTS: Three hundred twenty residents completed civilian family practice residency programs in Florida from 1986 through 1990. Only nine (2.8%) delivered babies the first year after residency. The major reasons that third-year residents gave for not planning to deliver babies included fear of being sued and the cost of malpractice insurance. Residents' estimates of first-year insurance costs were 350% higher than actual premiums. Furthermore, residents believed that the risk of being sued for the obstetrics portion of their practice would exceed the risk for the nonobstetric portion. CONCLUSIONS: Residents' estimates of the cost of malpractice insurance and their malpractice risk for delivering babies appear to be greatly exaggerated. These views are primarily obtained from nonresidency sources. PMID- 8482939 TI - Occupational Safety and Health Administration regulations for the physician's office. AB - Mandatory reporting and recordkeeping on job safety were established for all employers by the Occupational Safety and Health Administration (OSHA) Act of 1970. Physician interest in OSHA regulations recently increased with the publication of the Bloodborne Pathogens Standard. This review examines general employer communication to employees about new standards as well as reporting requirements for physician offices, including special OSHA forms needed to comply with illness and injury reporting. PMID- 8482940 TI - Insomnia: concerns of the family physician. AB - Insomnia is frequently seen in the primary care setting. Although poor sleep can impair daytime functioning and directly affect quality of life, insomnia often goes untreated, resulting in perpetuation and, sometimes, exacerbation of the problem. Reversing this trend requires that family physicians become attuned to complaints of insomnia and respond appropriately. Through education about proper sleep hygiene and stress management, and with the appropriate use of hypnotic agents, most cases of insomnia can be managed effectively by the primary care physician and patient without referral to a sleep specialist. PMID- 8482941 TI - Bell's palsy in pregnancy and the puerperium. AB - The incidence of Bell's palsy is significantly higher during the last trimester of pregnancy and the puerperium. Suggested explanations for this association include fluid retention, hypertension, compromise of the vasa nervorum, infection (particularly with herpes simplex virus), and an autoimmune process. The diagnosis is confirmed by identifying lower motor neurone paralysis and excluding secondary causes for the symptom complex. The majority of cases resolve spontaneously. Recovery may be delayed or incomplete in older patients and those with recurrent episodes or severe initial symptoms. The role of diuretics, steroids, or surgical decompression in treatment of pregnancy-related cases of Bell's palsy has not been well studied. PMID- 8482942 TI - Dermal complication of the bowel bypass syndrome: a case report. AB - Bowel bypass surgery, which involves shortening the small bowel to about 45 cm, is a modality of treatment for morbid obesity. Although this procedure is not routinely performed today, patients with complications from this procedure are still seen by physicians. The case of a patient who had bowel bypass surgery and experienced subsequent complications is discussed. PMID- 8482943 TI - Management of suspected perforation following colonoscopy: a case report. AB - Early detection of colon cancer is imperative for a good prognosis. Family physicians are therefore becoming the front line of defense in the fight against colorectal malignancy. Many family physicians are incorporating colonoscopy into their practices in an attempt to avoid costly referrals and loss of continuity of care. While the complication rate for colonoscopy is extremely low, any physician who performs colonoscopy must be fully aware of all possible complications and their management. PMID- 8482944 TI - A new triterpene glycoside from the roots of Symphytum officinale. AB - Chemical investigation of the EtOH-soluble portion of Symphytum officinale roots has resulted in the isolation of a new pentacyclic triterpene glycoside of oleanolic acid. Its structure was elucidated by spectroscopic studies, including 2D nmr, and chemical evidences as 3-O-[beta-D-glucopyranosyl-(1-->4)-beta-D glucopyranosyl-(1-->4)-alpha-L -arabinopyranosyl]-oleanolic acid [1]. PMID- 8482945 TI - Appenolides A-C: three new antifungal furanones from the coprophilous fungus Podospora appendiculata. AB - Appenolides A [1], B [2], and C [3], three new antifungal 2(5H)-furanones, have been isolated from liquid cultures of the coprophilous fungus Podospora appendiculata (UAMH 7225) by repeated preparative tlc on Si gel. The structures were assigned on the basis of nmr and ms data. PMID- 8482946 TI - Isolation of pseudoprototimosaponin AIII from rhizomes of Anemarrhena asphodeloides and its hypoglycemic activity in streptozotocin-induced diabetic mice. AB - A hot-H2O extract of rhizomes of Anemarrhena asphodeloides, the Japanese sino medicine "chimo," lowered the blood glucose level in alloxan-diabetic mice. Hypoglycemic activity-guided fractionation isolated a new glycoside, pseudoprototimosaponin AIII [1], which was compared with chemically known prototimosaponin AIII [2]. These compounds exhibited hypoglycemic effects in a dose-dependent manner in streptozotocin-diabetic mice but showed no effects on glucose uptake and insulin release, suggesting that the hypoglycemic mechanism may be due to inhibition of hepatic gluconeogenesis and/or glycogenolysis. PMID- 8482947 TI - Alkaloids from bufonid toads (Melanophryniscus): decahydroquinolines, pumiliotoxins and homopumiliotoxins, indolizidines, pyrrolizidines, and quinolizidines. AB - Skins of bufonid toads of the genus Melanophryniscus contain several classes of alkaloids: decahydroquinolines, pumiliotoxins, allopumiliotoxins, homopumiliotoxins, both 3,5- and 5,8-disubstituted indolizidines, 3,5 disubstituted pyrrolizidines, and a 1,4-disubstituted quinolizidine. Tricyclic alkaloids, including precoccinelline [193A] and alkaloid 236, an oxime methyl ether, are present in one population of Melanophryniscus stelzneri. PMID- 8482948 TI - Triterpenoid saponins from Gouania lupuloides. AB - The stems of Jamaican chawstick, Gouania lupuloides, have yielded two novel 16,17 seco-dammaranoid saponins, designated gouanoside A [4] and gouanoside B [5]. Structural assignments are based on spectroscopic data including 2D nmr experiments on the corresponding aglycones, gouanogenin A [1] and gouanogenin B [3]. PMID- 8482949 TI - Luffariolides F and G, new manoalide derivatives from the Okinawan marine sponge Luffariella sp. PMID- 8482950 TI - Penfield's homunculus: a note on cerebral cartography. PMID- 8482952 TI - Emanuel Swedenborg (1688-1772). PMID- 8482951 TI - Acute neuromuscular respiratory paralysis. PMID- 8482953 TI - Infarct topography and hemiparesis profiles with cerebral convexity infarction: the Stroke Data Bank. AB - For the 183 of 1276 patients in the NINDS Stroke Data Bank with convexity infarction in the middle cerebral artery territory, the size of the infarct did not differ between the two sides but the location of the main site of the infarct differed: on the left side, it was centred in the inferior parietal region, and was mid-frontal on the right. There was a good correlation between infarct size and weakness severity whether estimated by overall motor function on one side, arm, or hand alone. There was a poor correlation, however, for lesion location (lower third, middle third or upper third on either side of the Rolandic fissure) and any of the specific syndromes of focal weakness, no two cases sharing the same lesion for the same syndrome and several cases sharing the same lesion with a different syndrome. The findings indicated a difference in weakness syndromes between the two hemispheres and great individual variation of the acute syndrome caused by a given site of focal infarction along the Rolandic convexity. These variations may explain some of the difficulties showing effects of a given therapeutic agent in studies of acute ischaemic stroke. Large sample sizes will be required for the reliable assessment of any treatment using currently popular clinical stroke scales. PMID- 8482954 TI - The experiences of an acute stroke unit--implications for multicentre acute stroke trials. AB - The suitability of 200 consecutive patients admitted to a newly established acute stroke unit was assessed for participation in two multicentre trials currently in their pilot phase: the International Stroke Trial of aspirin and heparin, and the Multicentre Acute Stroke Trial of streptokinase versus placebo. Of the 200 patients (74 men, 126 women, mean age 71 years), 96% had cerebral CT, and 94% had a final diagnosis of cerebrovascular disease. Overall, 50% of patients presented within 6 hours and 70% within 12 hours of the onset of ictus. A total of 113 patients (56.5%) were potentially eligible for trial treatment with aspirin/heparin. Only 9 patients (4.5%) were eligible for streptokinase treatment: 50% were excluded because they presented after 6 hours; 23% had a previous stroke with clinical sequelae and 23% had severe systemic illness. Forty eight per cent of patients had more than one exclusion criterion. The potentially high enrollment rates in trials of antithrombotic agents contrast with the restricted recruitment for trials of streptokinase, emphasising the need for multiple centres to achieve useful study enrollment. PMID- 8482955 TI - Patterns of blood-brain barrier impairment and clinical features in multiple sclerosis. AB - Seventy four patients with clinically definite multiple sclerosis were studied by using polyacrylamide gel electrophoresis of cerebrospinal fluid to assess blood brain barrier function. Blood-brain barrier impairment was associated with recent clinical relapses of multiple sclerosis and worsened across a spectrum from the relapsing-remitting type of multiple sclerosis to secondary and primary progressive disease. The association between blood-brain barrier impairment and primary progressive disease is particularly interesting in the light of recent evidence that focal gadolinium enhancement on MRI is relatively unusual in patients with this disease. PMID- 8482956 TI - Congenital cervical spinal muscular atrophy: a non-familial, non progressive condition of the upper limbs. AB - Two patients with congenital cervical spinal muscular atrophy had symmetrical severe muscle weakness and wasting confined to the upper limbs, areflexia and congenital contractures. The shoulders were internally rotated, elbows extended and wrists flexed. There were no sensory or bulbar symptoms, scoliosis, long tract signs or lower limb involvement. This condition should be regarded as a neurogenic type of arthrogryposis, limited to the upper limbs. PMID- 8482957 TI - Focal electroencephalographic abnormalities and computerised tomography findings in children with seizures. AB - A persistent focal abnormality was observed in 157 (16%) electroencephalograms undertaken in 964 consecutive children with epileptic and non-epileptic seizures seen over one year. CT head scans were performed in 121 (77%) of the 157 children with a focus on the EEG; 26 (21%) showed an abnormality, and 21 (81%) of the abnormalities were localised. There was no difference in the proportion of abnormal scans associated with a delta or slow wave focus compared with a spike or sharp wave focus. An abnormal scan was uncommon after a single seizure. In only two patients (1.7% of all scans) did the findings on CT alter or greatly influence subsequent management. PMID- 8482958 TI - Association of HLA-Bw46DR9 combination with juvenile myasthenia gravis in Chinese. AB - One hundred and fifty two Chinese patients with myasthenia gravis in Taiwan were investigated for HLA-A, B, C and DR/DQ typing. HLA-Bw46 and DR9 frequencies were significantly increased in patients compared with the control group, and there was a decrease in DR3. Further analysis between different subgroups of patients showed Bw46 and DR9 were more significantly increased in the juvenile group than in the adult group. No single HLA allele was associated with either clinical type or thymic pathology, but there was an excess of BW46DR9 combination in both juvenile and ocular type patients. The Chinese population with myasthenia gravis is characterised by earlier age at onset, more ocular forms and less clinically severe illness than in whites, and these characteristics indicate a special subgroup that correlates with the strong Bw46DR9 association. PMID- 8482959 TI - Patients with spastic hemiplegia at different recovery stages: evidence of reciprocal modulation of early/late reflex responses. AB - Reflex electromyographic (EMG) muscle responses were recorded from abductor pollicis brevis (APB) and tibialis anterior (TA) muscles of fifty patients with spastic hemiplegia. Responses in the muscles were evoked during voluntary muscle contraction (about 20% of maximum voluntary effort) by submaximal but suprathreshold electrical stimulation of the median (at the wrist) and common peroneal (at the neck of the fibula) nerves respectively. Three EMG peaks (R1, R2 and R3) could be recorded after the direct muscle response (M). There was only a slight difference in R1-R2 latency interval of about 5 ms between upper and lower limbs on the unaffected side of the patients making it unlikely that this late response of the lower limb involves a long loop pathway, although this possibility cannot be discounted for the later, R3, response. Reflex behaviour was analysed for three clinical identifiable recovery stages of voluntary movements in the spastic limbs (synergistic, isolated and useful movements). The major finding was that an increase in the amplitude of the early response "R1" was associated with a decreased amplitude and delayed latency of the late response "R2" on the spastic side. The amplitude of R1 in the three different recovery stages decreased significantly, whereas the amplitude of R2 increased significantly with improvement of the functional stage of the limb. A significant negative linear correlation was found between R1 and R2 amplitude changes in upper as well as lower limbs. A refractoriness of the motor neuron pool as a possible explanation for the decreased R2 amplitude could be discounted. These findings together with recent work on reflex development in children support the hypothesis of reciprocal modulation of early and late reflex signals by supraspinal motor centers. PMID- 8482960 TI - Changes in sensation after nerve injury or amputation: the role of central factors. AB - Dynamic changes in somatosensory cortical maps are known to occur in experimental animals subjected to peripheral nerve transection or amputation. To study the sensory effects of central nervous system adaptation to temporary or permanent loss of input from a part of the hand, multimodality quantitative sensory tests were carried out in 11 patients with complete traumatic division and repair of the median or ulnar nerves and in six patients who had undergone amputation of one or more digits. As expected, vibration, two point discrimination, and tactile thresholds were raised in the territory of the injured nerve in a graded fashion, sensitivity being poorest in the patients with the most recent injuries. Surprisingly, localisation was better in the tips than at the base of the hypoaesthetic fingers, suggesting a central attentional gradient. Stimulus response curves conformed to a power function whose exponent was higher in denervated than in normal skin. Changes in psychophysical functions were also discernible in the intact hand. There was no hyperaesthesia in the territory of the nerve adjacent to the injured one or in the stump in the case of amputees. Central factors contribute to the sensory changes seen after nerve injury, but the functional effects of the cortical reorganisation that follows partial deafferentation are more subtle than a simple heightening of sensitivity in the surrounding skin. PMID- 8482961 TI - The relationship between visuospatial ability and perceptual motor function in Parkinson's disease. AB - To assess the contribution of visuoperceptual function to complex visuomotor responding in Parkinson's disease, 14 patients with idiopathic PD and 12 normal controls matched for age, education and general intellectual function were administered a visual tracing task. No difference was found between the groups on two visuoperceptual tests, the Benton Line Orientation test and a test of trajectory judgement. However, patients were significantly impaired in tracing a sawtooth design when two consecutive angles of the sawtooth were occluded. This impairment occurred in reproducing the basic form of the stimulus and not with accuracy of fine detail. These results suggest higher-order perceptual motor dysfunction independent of any breakdown in basic visuoperceptual processing or loss of fine motor control. It is concluded that Parkinsonian patients are unable to use sensory information accurately to plan and execute complex or new movements. PMID- 8482962 TI - Course and outcome of patients in vegetative state of nontraumatic aetiology. AB - A follow up study is reported of 100 consecutive unconscious patients admitted to an intensive care coma facility with a history of 30 days or more of unconsciousness of nontraumatic cause. Twenty recovered consciousness, all within 5 months of injury. 31 of the remaining patients died within 6 months following injury, while 49 continued unconscious until death. The mean life expectancy of these 49 was 26-34 months from that time. All 20 patients who recovered awareness continued to suffer from major disability. The prognosis for life or death and for recovery or not of consciousness was not significantly correlated with age or aetiology of the vegetative state. Among those who recovered consciousness, the younger patients showed somewhat better results in three parameters of function: locomotion, ADL and day-placement, but not in cognition, behaviour or speech accuracy and fluency. The overall results for these nontraumatic patients with postcomatose unawareness are clearly worse than those for patients with a similar period of unconsciousness following craniocerebral trauma. PMID- 8482963 TI - Long-term outcome of head injuries: a 23 year follow up study of children with head injuries. AB - The purpose of the 23 year follow up study was to determine the relationship between trauma variables including measures of head injury and very long-term sequelae. The study included 159 individuals with a mean age 31.40 years, of whom approximately 90% were admitted to hospital with a mild head injury during childhood (mean age 7.96). Extent of head injury was determined by unconsciousness, neurological status, skull fracture, EEG, post-traumatic seizures and a composite measure. The composite measure of neurological variables was the best predictor of long-term outcome. In addition, IQ recorded in the post acute phase was a reliable predictor of long-term outcome. Of the sample, 32.7% reported physical complaints and 17.6% reported current psychological/psychiatric problems unrelated to the head injury. Subjective sequelae (physical, intellectual and emotional) specified as due to the head injury were reported by 31% of the sample, and the sequelae were found to be related to the extent of the head injury and initial IQ. There were no discernible relationships between attribute variables including premorbid status and age with subjective sequelae. There were, however, significant relationships between subjective sequelae and objective, psychosocial measures of adaptation including educational lag, unemployment, current psychological/psychiatric problems and relationships with family members. Finally, there appeared to be continuity of complaints elicited during the five year follow up of the original project and current sequelae. The severity of the head injury was identified as the primary contributory factor in the reconstitution process and in the prediction of long term outcomes. PMID- 8482964 TI - Migraine madness: recurrent psychosis after migraine. AB - A 69 year old man with longstanding migraine with aura had four episodes of psychosis lasting 7-28 days during a 17 year period. During attacks he had formed visual hallucination and delusions, including reduplicative paramnesia. His mother was similarly affected. His EEG showed symmetrical frontal delta waves. The time course and EEG changes are similar to acute confusional migraine. The reduplicative paramnesia suggests a focal non-dominant hemisphere dysfunction. PMID- 8482965 TI - Coding of movement direction and amplitude in Parkinson's disease: are they differentially impaired (or unimportant)? AB - A recent study suggested that the preparation of movement direction, but not amplitude, may be selectively impaired by Parkinson's disease (PD). The authors examined the reprogramming of direction only, amplitude only, and direction and amplitude together, and included a control condition in which neither parameter was reprogrammed. The findings suggested that neither direction nor amplitude coding was differentially impaired in PD. Thus the structures affected by PD may not be uniquely involved in specifying only the direction or the amplitude of future movements; these structures probably have more complex higher-level roles. PMID- 8482966 TI - Acute upside down reversal of vision in vertebrobasilar ischaemia. PMID- 8482967 TI - Subcortical environmental reduplication: SPECT findings in a patient with a right thalamocapsular haemorrhage. PMID- 8482968 TI - Evidence for presynaptic inhibition on trigeminal primary afferent fibres in humans. PMID- 8482969 TI - Intracranial hypertension following psittacosis. PMID- 8482970 TI - Neurogenic effects on the palatopharyngeal muscle in patients with obstructive sleep apnoea: a muscle biopsy study. PMID- 8482971 TI - Risk of stroke in TIAs with a cerebral infarct on CT. PMID- 8482972 TI - Diabetes and stress hyperglycaemia in stroke. PMID- 8482973 TI - Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function. AB - Some CSF protein abnormalities have been proposed as a possible marker for vascular dementia. We studied the CSF protein levels and albumin ratio in 21 patients (mean age 64.04 +/- 7.5) with progressive bilateral motor impairment, and a CT picture of leucoaraiosis. Seven of these patients also presented with dementia. Twenty-seven Alzheimer's disease patients (mean age 59.59 +/- 5.30) without leucoaraiosis were taken as controls. We also evaluated the correlations of the albumin ratio values with the diagnosis of dementia, the severity of cognitive impairment, the degree of cerebral atrophy and presence of infarcts on CT, and the abnormalities in CSF circulation, found on isotopic cisternography, in the leucoaraiosis group. After controlling for age and sex, the patients with leucoaraiosis showed greater CSF albumin levels (0.27 g/l +/- 0.11 vs. 0.21 g/l +/- 0.06; covariance analysis P = 0.066), CSF IgG values (4.68 mg/100 ml +/- 1.45 vs. 2.85 mg/100 ml +/- 1.03; covariance analysis P < 0.001), and a higher albumin ratio (0.0078 +/- 0.0027 vs. 0.0058 +/- 0.0019; covariance analysis P = 0.013) than those with Alzheimer's disease. The variations of these parameters were not apparently related to the presence of dementia in the leucoaraiosis group. A significantly higher albumin ratio was observed in patients with a slowed CSF circulation compared to those with normal CSF circulation (0.0086 +/- 0.0028 vs. 0.0059 +/- 0.0019; covariance analysis P = 0.05). We conclude that, independently from the presence of dementia, patients with leucoaraiosis have CSF abnormalities consistent with functional blood-brain barrier alterations. PMID- 8482974 TI - The Extended Disability Status Scale (EDSS) as a predictor of impairments of functional activities of daily living in multiple sclerosis. AB - We investigated the relationship between the Kurtzke expanded disability status scale (EDSS) and an activities of daily living (ADL) scale that assesses disability across multiple functional domains based on self report of patients with multiple sclerosis (MS). Forty-three patients with definite MS responded on a 42-item ADL inventory and were also assigned an EDSS rating as part of their regular clinical examination. While a strong correlation was found between the EDSS and total ADL disability level, the ADL domain of 'Mobility' fully accounted for this relationship. The distribution of ADL scores as a function of EDSS level was curvilinear, as ADL variance was inconsistent across EDSS levels. Little ADL disability was evident when EDSS levels were below five. At higher EDSS levels, ADL variability increased substantially, making predictions regarding ADL level less exact. PMID- 8482975 TI - 6-[18F]fluorodopa metabolism in patients with hemiparkinsonism studied by positron emission tomography. AB - A group of 10 healthy control subjects and 10 patients with hemiparkinsonism (HD) were studied by positron emission tomography (PET) using 6-[18F]fluorodopa (FDOPA). FDOPA metabolism in the caudate nucleus and the putamen was separately estimated by measuring target-to-background ratios (TBRs) using composite images added between 30 and 60 min after FDOPA injection and by TBR-versus-time slopes during PET study. TBRs in the caudate nucleus and the putamen were 1.81 +/- 0.23 (mean +/- SD) and 1.92 +/- 0.28 in the 10 controls, respectively. In HD patients, on the dominantly affected hemisphere related to main clinical symptoms, TBRs were significantly decreased in the caudate nucleus (P < 0.01) and the putamen (P < 0.05) compared with those in the corresponding areas on the contralateral hemisphere, though those TBRs on both hemispheres were significantly decreased compared with the TBRs of normal subjects (P < 0.01). TBRs and TBR slopes in both the caudate nucleus and the putamen were correlated with disease severity according to Hoehn and Yahr. On the dominantly affected hemisphere, TBR and TBR slopes in the putamen were well correlated with individual clinical measures for bradykinesia and rigidity, and those in the caudate nucleus were also correlated with the severity of tremor. Our data suggest that in HD patients, PET study using FDOPA may provide unique and efficient information on the dysfunction of the dominantly affected caudate nucleus and the putamen which are correlated with diseased severity and individual clinical symptoms. PMID- 8482976 TI - Cerebral glucose metabolism and striatal 18F-dopa uptake by PET in cases of chorea with or without dementia. AB - Cerebral glucose metabolism was studied by positron emission tomography with [18F]fluorodeoxyglucose in 12 patients with chorea due to different underlying diseases. The striatal 18F-dopa uptake was also studied with 6-L-[18F]fluorodopa in 6 of them. Five of them were diagnosed as Huntington's disease two were as 'sporadic progressive chorea and dementia' with characteristic symptoms and signs of Huntington's disease but no family histories, two were as choreoacanthocytosis, and two had hemichorea caused by suspected vascular lesions in the contralateral striatum revealed by MRI. Caudate and putaminal glucose metabolism decreased in chorea compared to the controls. Hemichorea showed decreased glucose metabolism only in the contralateral striatum. Moreover the glucose metabolism decreased in demented each 7 patients in the frontal, temporal and parietal cortices as well as in the striatum. The caudate and putaminal 18F dopa uptake in patients with chorea showed no difference with that in the controls. The pathogenetic mechanism of chorea may involve decreased glucose metabolism and normal presynaptic dopaminergic activity in the striatum, and that of the demented state in chorea may also involve an additional decrease of the glucose metabolism in the frontal, temporal and parietal cortices. PMID- 8482977 TI - Mitochondrial DNA mutations at nucleotide positions 3243 and 3271 in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a comparative study. AB - Of 50 patients with the clinical characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 38 had a point mutation at nucleotide position (nt) 3243 in the tRNA(Leu(UUR)) region in mitochondrial DNA and 6 at nt 3271 in the same tRNA(Leu(UUR)) gene. Except for the later onset of the disease in the patients with the 3271 mutation, there were no clinical, biochemical and pathological differences between the two groups. Since the nt 3271 region is not located in the binding site for mitochondrial transcription termination (mTERM) factor, which has been proposed to be defective in the 3243 mutation, a functional defect in tRNA itself might be responsible for the enzyme defects in MELAS patients; however the mechanism by which the defective tRNA(Leu(UUR)) induces the stroke-like episodes remains to be clarified. PMID- 8482978 TI - Heparin treatment in patients with human T-lymphotropic virus type I (HTLV-I) associated myelopathy: a preliminary study. AB - Ten patients with HTLV-I-associated myelopathy (HAM) were treated in an uncontrolled preliminary trial of heparin. In 7 patients, motor dysfunction improved substantially and the effect continued for more than a month after the discontinuation of therapy. Sensory and urinary disturbances also improved in 3 of 4 and in 2 of 10 patients, respectively. Heparin did not alter the subsets of peripheral blood lymphocytes nor the titers of anti-HTLV-I antibodies in serum and cerebrospinal fluid. Spontaneous proliferation of peripheral blood lymphocytes, however, was depressed significantly (P < 0.05) in all cases. Heparin therapy has some advantages in cost, ease of administration and fewer side effects compared to other therapies such as plasmapheresis and interferon alpha. We conclude that heparin can be administered safely to HAM, and that a double-blind placebo-controlled trial is warranted to determine its efficacy in HAM. PMID- 8482979 TI - The innervation of human epidermis. AB - Using immunohistochemical procedures numerous nerve fibers have been found in all cell layers of human epidermis. These nerves originate from nerve trunks in the dermis, enter the epidermis, then divide distally to eventually end in small enlargements, near the surface of the skin and in deeper areas. Some endings may be external to stratum granulosum cells. Epidermal nerves appear to have a three dimensional territorial distribution in relationship to the skin's surface. The presence of epidermal nerve fibers was confirmed by electron microscope studies. The nerves are presumed to be sensory in nature. The existence of epidermal nerve fibers will necessitate changes in present theory of structure and function of peripheral sensation. PMID- 8482980 TI - Repair of N-methylpurines in DNA from lymphocytes of patients with amyotrophic lateral sclerosis. AB - We have previously reported reduced ability of ALS fibroblasts to repair genomic DNA damage produced by alkylating agents. This report presents our experience of studying DNA repair in lymphocytes from ALS patients. The repair of N methylpurines produced by treatment with the alkylating agent, methyl methanesulfonate, was studied in T-lymphocytes from patients with sporadic and familial ALS, and appropriate controls. Repair of damage was quantitated by using alkaline elution for genomic DNA repair, and methoxyamine protection of abasic sites in DNA fragments for gene-specific repair in the dihydrofolate reductase (dhfr) gene, at time points 0, 6 h and 24 h. No significant repair rate differences were observed between ALS and control lymphocytes in either genomic or gene-specific DNA repair. The possible reasons for the discrepancy with our earlier results in lymphocytes and fibroblasts are discussed. PMID- 8482981 TI - Dystrophin isoforms expressed in the mouse retina. AB - The dystrophin gene is expressed in various tissues of the mouse. Previous immunohistochemical studies suggested the existence of dystrophin protein in the outer plexiform layer of the retina. We analyzed mRNAs from the retina and other tissues of mice and detected the dystrophin transcripts (DT) with the use of the reverse transcription and polymerase chain reaction (RT-PCR) method. The 5' sequences, corresponding to the first exon, of DT in the retina was mainly the brain type, whereas in the 3' region of DT that corresponds to the C-terminal domain of dystrophin, some additional RT-PCR products were detected. Base sequences in three of them showed homology to those for previously reported human dystrophin isoforms. The DT variations in mice were identical between the retina and the brain. It was thus concluded that dystrophin really expresses in the mouse retina and most of the retinal dystrophin proteins belong to the brain type isoform. PMID- 8482982 TI - Age-dependent decline in cognitive information processing of HIV-positive individuals detected by event-related potential recordings. AB - Cognitive event-related potentials (ERP) were recorded in 100 HIV-positive patients of all CDC stages without clinical CNS deficits with an auditory oddball paradigm. Four latency peaks and three amplitudes were evaluated (N1, P2, N2 and P3 latencies, N1-P2, P2-N2 and N2-P3 amplitudes). In contrast to an age-matched control group of comparable education and social environment, a statistically significant N2-P3 amplitude reduction was found in the patient group deteriorating with the CDC stages. The physiological N2-P3 amplitude reduction with age in normals was found to be twice as fast in HIV-positive individuals. No group-statistically relevant EEG abnormalities were found in the patient group. In psychometric testing, there was no marked depressive syndrome in the HIV positive individuals, but a mild slowing of speed-dependent abilities. PMID- 8482983 TI - Plasma lipoproteins in cortical infarction versus transient ischaemic attacks: a case control study. AB - The authors investigated the relationship between plasma lipids and the risk for cortical infarction (61 cases) and transient ischaemic attacks (TIA) (35 cases) compared with matched controls. They observed a maximal increase of total cholesterol, of very low-density lipoprotein and low-density lipoprotein (LDL), triglycerides, total apolipoprotein (Apo), B,LDL-Apo B and Apo-A1, and small size high-density lipoprotein (HDL) and large size HDL whose separation was not possible. In contrast they observed a decrease of HDL-ApoE, a distribution of LDL in a single fraction and the presence of LDL of low weight in the group with cortical infarction with or without cardiac arrhythmias. For the first time, we describe a decrease of the HDL-ApoE/total ApoE ratio. TIA differed from the former group by a low level of HDL and the lack of abnormalities of Apo-A1, distribution of small and large size HDL, and in the distribution and the weight of LDL. These data suggest that previously demonstrated differences in LDL cholesterol and HDL-cholesterol levels between patients with ischaemic stroke and control subjects may apply to patients with cortical infarction, and that in TIA there are changes in the distribution and the weight of LDL. PMID- 8482984 TI - Physiological assessment of aspects of autonomic function in patients with secondary progressive multiple sclerosis. AB - A detailed non-invasive study of systemic and regional haemodynamic responses to a range of autonomic tests which assess sympathetic and parasympathetic pathways (mental arithmetic, cutaneous cold, isometric exercise, deep breathing, Valsalva manoeuvre and head-up tilt) were performed in ten patients with secondary progressive multiple sclerosis and ten age- and sex-matched healthy normal subjects (controls). Blood pressure rose in controls during the pressor tests and was maintained during tilt. In six out of ten patients with multiple sclerosis blood pressure was unchanged during one or more of the three pressor tests, but was maintained in all during tilt. In the controls, superior mesenteric artery blood flow fell during pressor tests and head-up tilt. In multiple sclerosis patients, superior mesenteric artery blood flow did not change during pressor tests but fell during tilt. Cardiac index rose during isometric exercise and fell during head-up tilt in controls. Forearm blood flow rose during mental arithmetic in the controls only, but fell during tilt in both groups. Individual analysis indicated that of the ten multiple sclerosis patients, four had responses during the pressor tests similar to controls. Responses to deep breathing and to the Valsalva manoeuvre in controls and multiple sclerosis patients were similar. We conclude that some patients with an aggressive and disabling form of multiple sclerosis have selective autonomic dysfunction, in particular involving pressor responses, despite the lack of postural hypotension. The autonomic abnormality is likely to involve central autonomic interconnections rather than afferent or sympathetic efferent pathways. Further clarification of the nature, site and progression of these lesions is needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482985 TI - Ceruletide therapy in action tremor following thalamic hemorrhage. AB - Two men, aged 63 and 71 years, developed a gross action tremor and dysesthesias several months after an intracerebral hemorrhage. CT and MRI showed a small hemorrhage in the posterior region of the lateral nucleus of the thalamus in each patient. The tremor occurred on movement, had frequencies of 2.5-4.5 Hz and the amplitude varied depending on the joint position of the limb. Ceruletide (a cholecystokinin analog) 0.8 micrograms/kg i.m. produced a marked reduction in the action tremor and improved motor function. This effect appeared 10-15 min after the injection, and lasted for up to 4 weeks. It is suggested that ceruletide may be of value in the treatment of action tremors following a thalamic lesion. PMID- 8482986 TI - Influence of repetitive magnetic stimuli on verbal comprehension. AB - The influence of repetitive magnetic transcranial stimulation over the temporo parietal cortex on verbal comprehension was investigated in 44 healthy subjects. In right-handed subjects, trains of 50 Hz magnetic stimuli over the left hemisphere produced more errors than stimulation over the right hemisphere. The result is not very clearcut, however; thus the test cannot be used for diagnostic investigation of language dominance. PMID- 8482987 TI - On the genetics of complex partial seizures: waking and sleep EEGs in siblings. AB - Waking and sleep EEGs were recorded in 29 siblings of 19 patients with complex partial seizures. At least 1 sibling with epileptic activity (EA) was found for 36.8% of the patients. Taking the 29 siblings as a basis, in 7 EA was recorded. Most EA was seen during sleep in stage C (29%). More EA was recorded in female siblings (28%: 18%) and in siblings of female patients (56%: 20%). All EA was seen in the age range 5-14 years. Siblings with occipital theta-delta activity with a generalization tendency showed more EA (59%) than those without this pattern (8%). Of the siblings of patients with generalized EA 50% showed EA, but only 25% of those of patients with localized EEG patterns. PMID- 8482988 TI - Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor. AB - To evaluate the effects of the aldose reductase inhibitor Ponalrestat (Statil) on diabetic autonomic neuropathy, a double-blind placebo controlled trial was carried out on a group of 34 diabetic patients with documented cardiac autonomic neuropathy. After a 4-week, placebo run-in period, patients were randomised for treatment with 600 mg Statil or placebo for another 24 weeks. Moreover, the reliability of the autonomic nerve function tests was investigated by comparing the results at onset and at week 4. Fifteen patients treated with Statil and 12 with placebo completed the study. Neither symptom scores nor cardiovascular reflexes, pupil reflexes and skin vasomotor reflexes improved after Statil therapy, which led us to conclude that Statil is not effective in the treatment of diabetic autonomic neuropathy. Reliability coefficients for cardiovascular reflexes and pupil reflex showed high values, ranging from 60% to 80%. Therefore these methods are recommended in future therapy trials. PMID- 8482989 TI - The coordination of posture and voluntary movement in patients with hemiparesis. AB - Postural adjustments associated with the task of raising oneself on tiptoes were investigated in a reaction time paradigm in six normal subjects and six patients with hemiparesis due to stroke. Body and ankle position in space were measured by means of a movement analysis system (ELITE). The findings indicate that the task of going up on tiptoes is performed in two steps. First, the centre of gravity is shifted forward to a position perpendicular to the forefoot. This movement is initiated by a phasic burst of EMG activity in the tibialis anterior (TA). The activity of the quadriceps femoris (QUA) aids the forward shift and together with the biceps femoris (BF) stabilizes the knee. Following these postural adjustments, the action of going up on tip-toes is performed mainly by the gastrocnemius medialis (MG). The basic pattern of preparatory (TA, QUA, BF) and focal (MG) activity was disturbed in its temporal sequence in patients with hemiparesis. The analysis of the biomechanical data showed smaller movement velocities for leaning forward and going up on tiptoes in patients, with increased movement amplitude on the paretic side. In addition, the correlation between the start of horizontal (leaning forward) and vertical (going up on tiptoes) hip movement was lost in patients. The preserved correlation between the latency of MG activity and the onset of the vertical hip movement on the paretic side in patients and the loss of correlation on the non-paretic side indicates that the EMG activity on the healthy side is adapted to the functional requirements of the affected side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482990 TI - Follow-up of neurophysiological tests and CT in late-onset cerebellar ataxia and multiple system atrophy. AB - The follow-up of neurophysiological tests (brain-stem auditory evoked potentials; blink reflex; sensory, motor and visual evoked potentials) and CT was investigated in 21 patients with late-onset cerebellar ataxia (CA) or multiple system atrophy. The study included an initial investigation and a follow-up examination on average 25.3 months later (minimum 8, maximum 36). Patients were divided into four groups: (1) those with pure CA after a minimum course of 5 years; (2) those with pure CA with pathological neurophysiological findings at the last examination; (3) those who at the first examination clinically presented with pure CA, but at the last examination were seen to have developed a multisystem disorder; (4) those with multiple system atrophy (mostly olivopontocerebellar atrophy) presenting additional non-cerebellar signs of involvement. Conforming to a strict interpretation of pure CA, group 1 patients invariably exhibited normal neurophysiological findings at all examinations. All patients in group 4, except for 2 only at the first examination, showed pathological changes in at least one of the neurophysiological tests. The main conclusion of this paper is that individuals who according to clinical criteria were initially classified as having CA but finally developed a multisystem disorder already had pathological neurophysiological findings at the initial examination (group 3). The increasing frequency of pathology in the several neurophysiological tests together with the progression of the disease is obviously of prognostic significance. CT revealed cerebellar atrophy without apparent involvement of brain-stem structures in all patients with CA; the majority of patients with multiple system atrophy also had atrophy of the brain stem, pointing to olivopontocerebellar atrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8482991 TI - Friedreich's ataxia presenting with pure sensory ataxia: a long-term follow-up study of two patients. AB - We describe two patients with Friedreich's ataxia whose presenting symptomatology was for years progressive tabetic ataxia. Based upon the initial clinical, electrophysiological and nerve biopsy data, a diagnosis of idiopathic sensory neuropathy was established. Subsequent examination of the kin showed that three sisters of case 1 had Friedreich's ataxia. Upon serial clinical and electrocardiographic study, both patients eventually developed a florid Friedreich's ataxia, including cardiomyopathy. Our findings indicate that at onset Friedreich's ataxia may be indistinguishable from sensory neuropathy and also that serial examination and investigation of kinship are essential steps for accurate diagnosis. PMID- 8482992 TI - Decrease in urinary excretion of 3-methylhistidine by patients with Duchenne muscular dystrophy during glucocorticoid treatment. AB - Seven patients, aged 10-17 years, with Duchenne muscular dystrophy were treated orally with prednisolone (PSL) at a dose of 0.8-1.0 mg/kg per day for 8 weeks. During the treatment their muscle strength, serum creatine kinase (CK) activity, serum levels of myoglobin (Mb), and urinary excretion of 3-methylhistidine (3 MeH) and glycine (Gly) were measured serially. In all the patients, the motor function or muscle strength improved, and the serum CK activity and Mb level decreased during PSL treatment. Urinary excretion of 3-MeH, a unique constituent of muscle contractile proteins, decreased to 51-63% of the baseline value in weeks 6-9 after the start of PSL administration, and returned to the baseline level in week 12. The ratios of 3-MeH to creatinine and to Gly also decreased during the treatment. Urinary excretion of Gly, which is ubiquitous in all tissues including muscle, did not decrease during the treatment. These findings suggest that PSL inhibits proteolysis of muscle contractile protein. PMID- 8482993 TI - Local steroid treatment in idiopathic carpal tunnel syndrome: short- and long term efficacy. AB - A clinical and electrophysiological study evaluated the usefulness of local steroid therapy for carpal tunnel syndrome (CTS). To evaluate the efficacy of local steroid therapy 32 patients (53 nerves) were randomly assigned to one of two groups: one (27 nerves) received 15 mg methylprednisolone acetate injected locally and the other (26 nerves) received the same amount of saline solution. The injections were repeated after a week. Clinical and electrophysiological findings were evaluated, double blind, at regular intervals. A clear-cut efficacy of steroid treatment was found. Only 8% of nerves were not benefitted while a marked early improvement was observed in most of the nerves. In order to appraise the long-term effect of local steroid treatment on CTS, 53 patients (91 nerves) were studied and followed up by means of clinical and electrophysiological examinations performed every 2 months for 2 years. The benefit of steroid treatment was transient. About 50% of the nerves became worse within 6 months and 90% within 18 months. Only a small percentage (8%) of the nerves remained improved at the 2-years follow-up. The clinical features were not useful in foretelling the duration of the improvement, which appeared to be related to the antidromic SAP latency. PMID- 8482994 TI - Difference in blood flow volume of the common carotid artery between vascular and non-vascular dementia detected by colour duplex sonography. AB - Using colour duplex sonography, blood flow volume in the common carotid artery was measured in 72 demented patients and 28 normal controls. Thirty-five patients with a Hachinski's ischaemic score of 7 or above and marked ischaemic lesions on CT were assigned to the vascular dementia (VD) group. Thirty-three patients with probable Alzheimer's disease according to the NINCDS-ADRDA criteria, 2 patients with Parkinson's disease, 1 patient with spinocerebellar degeneration, and 1 patient with Pick's disease were assigned to the non-vascular dementia (nonVD) group. The sum of blood flow volume in the bilateral common carotid arteries (CCA flow) in the nonVD group and in the VD group was lower than that in the control group. The CCA flow in the VD group was lower than that in the nonVD group. Comparison of patients matched for both age and the Hasegawa's dementia rating scale also revealed lower CCA flow in the VD group than in the nonVD group. Linear discriminant function analysis showed that nearly 90% of the demented patients were correctly diagnosed as having VD or as having nonVD. These results show the usefulness of colour duplex sonography in the differential diagnosis of patients with dementia. PMID- 8482995 TI - Deterioration or onset of migraine under oestrogen replacement therapy in the menopause. PMID- 8482996 TI - A case of recurrent Guillain-Barre syndrome preceded by different infections. PMID- 8482997 TI - Dentine lead and intelligence prior to school entry: a statistical sensitivity analysis. AB - The relationship between circumpulpal dentine lead and IQ at age 4 years 10 months was examined in 164 urban children. Negative correlations were observed between dentine lead and IQ scores, but were reduced in magnitude after adjustment for social covariates. Analyses using errors-in-variables regression models indicated that the degree of this reduction depended on difficult-to verify assumptions regarding the magnitudes of (i) measurement error in the lead variable and the covariates, and (ii) possible changes in the caretaking environment resulting from conjectured effect of lead on the child's cognitive and behavioral development. Sensitivity analyses were conducted in which estimates of the lead effect were repeatedly computed and compared for a range of possible values for factors (i) and (ii). It was found that the statistical significance of the lead effect on Full Scale IQ depended on the relative magnitudes of these factors, and that failure to incorporate measurement error in the analysis would have led to gross overestimation of the precision of the findings. PMID- 8482998 TI - Non-response bias in studies of diabetic complications: the Rochester Diabetic Neuropathy Study. AB - Non-response can bias studies of disease conditions but its influence has rarely been evaluated due to limitations of available data on the non-respondents. Because of a detailed medical record review for eligibility, we were able to compare clinical as well as demographic characteristics of respondents and non respondents in a population-based study of diabetic complications among Rochester, Minnesota residents. Non-respondents were older, less well educated, more likely to be widowed and more often retired. They were much more likely to have cardiovascular disease at baseline, but the prevalence of retinopathy, nephropathy and diabetic neuropathy was similar for respondents and non respondents, who were also comparable with regard to type of diabetes and diabetic therapy. While these findings indicate that data from the Rochester Diabetic Neuropathy Study can probably be generalized to diabetic residents generally, they reemphasize the potential for non-response bias in epidemiologic studies of clinical conditions, especially cardiovascular disease. PMID- 8482999 TI - Role of the complete blood count in detecting occult focal bacterial infection in the young febrile child. AB - Previous studies of the value of the complete blood count (CBC) in distinguishing viral from bacterial infection in young febrile children have failed to exclude children with clinically evident bacterial infection and thus have inflated the positive predictive value of the test for occult focal infection. We prospectively studied 2492 children 3-24 months of age who presented to a children's hospital emergency department between March 1989 and August 1990 with fever (> or = 38.0 degrees C) of acute (< or = 4 days) onset but no evident bacterial focus of infection, 433 (17.4%) of whom received a CBC. We also carried out an 8-year retrospective analysis to estimate prior, or pre-test, probabilities (prevalences) and examine CBC results for rare occult bacterial infections (meningitis, osteomyelitis, and septic arthritis). Estimated prior probabilities for the four most common categories of infection that can be diagnosed at the initial visit were: non-pneumonitic viral infection, 88.6% in boys and 86.0% in girls; pneumonia, 8.5% in both sexes; urinary tract infection (UTI), 3.0% in boys and 5.5% in girls; and bacterial meningitis, 0.0066% in both sexes. The likelihood (sensitivity) of a total white blood cell (WBC) count > or = 15,000/mm3 was 25.5, 64.5, 62.5, and 50.0% for viral infection, pneumonia, UTI, and meningitis, respectively. Among children with a high total white blood cell count, neither a total polymorphonuclear count > or = 10,000/mm3 nor a band count > or = 500/mm3 was associated with significantly elevated likelihoods for occult pneumonia or UTI, a finding confirmed by multiple logistic regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483000 TI - The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis. AB - During 1978-1990, 346 patients with sarcoidosis were enrolled in our institute. Of 346 patients, 295 patients were eligible for evaluation on the clinical course and prognosis. According of their clinical presentations, they were classified into 3 groups; severe, moderate and mild sarcoidosis. Of the 295 patients, 27 (9.2%) were classified as severe sarcoidosis who developed serious illness including involvement of the heart (8), lung (6), muscles (5), eyes (3), central nervous system (CNS) (3) or liver (2). The mean interval between the onset of disease to severe disability was 58.3 months. The interval was particularly long in those patients who presented with either pulmonary (100.8 months) or liver sarcoidosis (108 months). Of the 27 patients with severe sarcoidosis, 8 (29.6%) gradually became worse towards the end of their clinical course despite only mild clinical signs and symptoms at the first presentation. Therefore, the initial clinical symptoms and findings, including ocular involvement. ECG abnormalities, negative reaction to PPD, high value of serum angiotensin converting enzyme (ACE) and a small number of lymphocytes in peripheral blood, were not useful in predicting prognosis. The relationship between the maximum serum ACE value during the clinical course and the duration of the active phase was statistically significant in the 123 patients who were monitored throughout their course, suggesting that the maximum serum ACE may be a marker for assessing prognosis. Corticosteroid was administered to 76 patients (22%) with serious systemic involvement. They included 26 (96.4%) of the 27 severe sarcoidosis and 50 (37.9%) of the 132 moderate sarcoidosis. Patients with mild sarcoidosis did not receive corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483001 TI - Interobserver variation in the assessment of the sampling quality of cervical smears. AB - In order to assess the interobserver variation among cytological assistants in evaluating the sampling quality of cervical smears, all four laboratory assistants from one cytological department examined the same set of 71 smears. They assessed the presence of endocervical cells, the quality of fixation, the number of cells and the undesirable presence of clumps of cells. The interobserver agreement, uncorrected for chance, varied from 73 to 93% for the presence of endocervical cells and from 86 to 100% for the three other criteria. For the presence of endocervical cells, the kappa values, a measure for the interobserver agreement corrected for chance, varied from 42 to 84%. This is a reasonable outcome. For the three other criteria many kappa values were zero or uncalculable. The interobserver agreement in evaluating the sampling quality of cervical smears is reasonable to good, but not perfect. Prudence in the interpretation of quality data is warranted. PMID- 8483002 TI - Is there still an avoidable fraction of post-operative thromboembolic complications with heparin prophylaxis? The results of a case-control surveillance. Collaborative Group on Heparin Prophylaxis in Surgery (S.E.P.E.C.). AB - A case-control multicenter study was set up in 68 general and specialistic wards in Italian regional hospitals in order to assess whether underuse of heparin prophylaxis may account for at least a fraction of the thromboembolic events still occurring in surgical patients. 100 cases with clinically relevant thromboembolic or hemorrhagic events occurring during hospitalization for major surgery and 200 controls were identified. Controls were selected among patients not presenting any of the events under study during the same period of observation and were matched with cases for age, sex, and type of surgery. The results of the study suggest that heparin use in routine conditions of care closely reflects the "consensus" knowledge, patients at higher risk (specifically orthopedic surgical patients, those with varicose veins or with preoperative bed rest longer than 3 days) being treated more frequently with heparin. Absence of heparin prophylaxis does not appear to represent a specific risk factor for the occurrence of index events (OR 0.73, 95% CI = 0.42-1.26). Despite the higher rates of heparin exposure, the presence of varicose veins is associated with a statistically significant increase in the risk of postoperative complications (OR 2.23, 95% CI = 1.07-4.65). This study indicates that among known pre- and peri operative risk factors only varicose veins may be unprotected by the current prophylaxis practice. PMID- 8483003 TI - The Duke Severity of Illness Checklist (DUSOI) for measurement of severity and comorbidity. AB - The Duke Severity of Illness Checklist (DUSOI) was evaluated on 414 primary care adult patients using data collected both by medical providers at the time of the patient visit and later by a chart auditor. Severity scores for individual diagnoses were determined by summing the ratings for four non-disease-specific parameters: symptom level, complications, prognosis without treatment, and expected response to treatment. Mean diagnosis severity scores (scale 0-100) among the 21 most prevalent diagnoses varied from a low of 13.9 for menopausal syndrome to a high of 43.0 for sprains and strains. An overall severity score was calculated by combining diagnosis severity scores and giving highest weights to the most severe diagnoses. Provider-generated overall severity scores (mean = 43.3) and auditor-generated overall severity scores (mean = 38.9) were significantly correlated (coefficient of agreement = 0.59, p < 0.0001). Diagnoses varied in their individual contribution to the overall severity score, from 8.9% for lipid disorder to 90.0% for sprains and strains. Separate comorbidity severity scores were calculated to measure the severity of all of each patient's health problems except the diagnosis under study. For example, patients with menopausal syndrome had co-existing health problems which generated a high mean comorbidity severity score of 43.2, while patients with sprains and strains had a low mean comorbidity score of 4.7. The DUSOI Checklist can be used in the clinical setting by both providers and auditors to produce quantitative severity scores (by diagnosis, overall, and for comorbidity) which are based entirely upon clinical judgment. This method should be useful in controlling for severity of illness in clinical studies and indicating the outcome of medical care in terms of reduction in severity of illness following medical interventions. PMID- 8483004 TI - Should there be early publication of ancillary studies prior to the first primary report of an unblinded randomized clinical trial? PMID- 8483005 TI - Dentine lead and intelligence prior to school entry: a statistical sensitivity analysis. PMID- 8483006 TI - Epidemiology of premenstrual symptoms. PMID- 8483007 TI - Effects of passive smoking. PMID- 8483008 TI - Effects of passive smoking. PMID- 8483009 TI - Use of prostaglandins for induction of labor. AB - Nurse-midwives are sometimes required to intervene in the normal process of labor. Numerous clinical trials have investigated the use of prostaglandins for induction of labor. Research indicates the use of prostaglandins to be a safe and effective method of induction of labor with favorable results when compared with the more traditional use of oxytocin. Patient acceptance appears to be favorable because of the reduced need for restrictive and invasive methods of monitoring and administration that accompany intravenous oxytocin. Thus, the use of prostaglandins for induction of labor offers nurse-midwives an attractive alternative to the use of oxytocin when induction is medically indicated. This article provides a description of the biochemical effects of prostaglandins on the uterus and cervix, development and clinical use of prostaglandin preparations, indications for use of induction, and potential for utilization in nurse-midwifery practice. PMID- 8483010 TI - Third-trimester ultrasound for nurse-midwives. AB - Obstetric ultrasound has become well integrated into management of pregnancy, labor, and delivery. An increasing number of nurse-midwives have expanded their roles to include the use of this technology. This article reviews the basic principles of ultrasound physics, the content of ultrasound examinations, and the performance of basic scans. The uses of limited scans for third-trimester antepartum assessment and intrapartum management are reviewed. Issues surrounding the use of obstetric ultrasound, including limited scans, routine ultrasound screening, and necessary education, are discussed. Information on incorporating the use of ultrasound procedures into nurse-midwifery practice is included. PMID- 8483011 TI - The use of amnioinfusion in nurse-midwifery practice. AB - Intrapartum amnioinfusion is being used in a variety of clinical settings and for multiple therapeutic modalities to prevent fetal distress and improve outcomes. The procedure has demonstrated efficacy in cases of variable decelerations and thick, meconium-stained amniotic fluid. Amnioinfusion has been shown to improve maternal and neonatal outcomes by decreasing cesarean sections for fetal distress, improving cord pH, and decreasing the amount of meconium present below the cords at delivery. This article describes the pathophysiology of amniotic fluid volume disorders that indicate the use of amnioinfusion, reviews the literature regarding the indications and therapeutic effects, and describes techniques for the use of amnioinfusion. In addition, there is a discussion of the contraindications associated with the use of amnioinfusion and its use in and out of hospital settings. The technique for amnioinfusion is simple, easy, and inexpensive to initiate. It can be performed in a variety of settings, provided there is adequate equipment, personnel, and emergency services available. Certified nurse-midwives should become familiar and comfortable with the procedure in order to provide complete care for the families they serve. PMID- 8483012 TI - External cephalic version. AB - External cephalic version has been used periodically for centuries to manage breech presentations. As cesarean section rates have escalated in the last two decades, ways to curb this rise have been evaluated. By reducing the number of infants that arrive in labor in a malpresentation, it is possible to impact the overall cesarean section rate. External cephalic version is a safe, effective method when used in appropriate cases of breech presentation. A forward or backward roll can be accomplished in women at term with singleton gestations, adequate amniotic fluid, and reactive nonstress tests. Parity, fetal and placental position, and descent of the presenting part may all influence the success rate of the version. PMID- 8483014 TI - Guide to the use of the vacuum extractor by nurse-midwives. AB - The vacuum extractor has become a widely used instrument in many settings. It has proven to be a reliable method of ensuring safe passage of the fetus and/or enhancing maternal effort during the second stage of labor. The principles of vacuum-assisted birth are learned relatively easily and have been incorporated into many nurse-midwifery practices. This article reviews the principles of vacuum extraction as they apply to the practice of nurse-midwifery. Vacuum extractors available to nurse-midwives are compared. Nurse-midwives are familiarized with vacuum extraction so that they can make an informed choice concerning the vacuum extractor as an appropriate tool within their practice. This article is not intended to teach nurse-midwives to use the vacuum extractor. It does, however, provide guidelines for credentialing those nurse-midwives choosing to incorporate the principles of vacuum extraction into their practice. PMID- 8483013 TI - Subdermal contraceptive implants in nurse-midwifery practice. AB - Subdermal contraceptive implants have only recently been approved for use in the United States. At present, only one subdermal contraceptive implant, Norplant, is approved in the United States. This article describes the development of Norplant, its efficacy and safety, a description of the system, education for clients, side effects, indications and contraindications, insertion and removal, incorporation into midwifery practice, and education for health professionals regarding its use. PMID- 8483015 TI - High-tech skills in low-tech hands. Issues of advanced practice and collaborative management. AB - Nurse-midwifery practice has been defined by the American College of Nurse Midwives (ACNM) as "the independent management of essentially normal newborns and women ... occurring within a health care system which provides for medical consultation, collaborative management or referral .... "As the health care delivery system in the United States becomes increasingly complex and reliant on new forms of technology, it has become necessary to clarify roles and responsibilities for the nurse-midwife. In addition, mechanisms for acquiring new skills and for collaborating with physician colleagues must be well understood. A question frequently asked is where the boundaries of nurse-midwifery practice end and those of medical practice begin. Although practice scenarios vary for individual nurse-midwives and nurse-midwifery services, recent statements approved by the ACNM Board of Directors discuss these issues in an attempt to clarify the potentially confusing areas of collaboration and skill acquisition. This article explores the areas of expanded nurse-midwifery practice and collaborative management. Although individual clinical skills are not necessarily endorsed, a step-by-step approach that nurse-midwives can use for incorporation of new skills is presented. The concepts discussed will be a valuable tool to nurse-midwives in their practice. PMID- 8483016 TI - Fetal scalp blood sampling. AB - Fetal scalp blood sampling (FSBS), in conjunction with fetal heart rate monitoring, is a method of fetal surveillance that may avoid cesarean delivery of the healthy fetus or indicate the need for immediate delivery of a compromised fetus. Some researchers have recently begun to question the efficacy of FSBS. In this article, three nurse-midwives discuss FSBS as a tool in assessing fetal well being during labor and consider whether FSBS is a nurse-midwifery procedure. PMID- 8483017 TI - Differences between calcium antagonists: duration of action and trough to peak ratio. AB - Comparison of first- and second-generation calcium antagonists: Despite their diversity of structure, the first-generation calcium antagonists nifedipine, verapamil and diltiazem all have a short elimination half-life and a relatively short duration of action. In contrast, there appears to be wide diversity in these properties among the newer calcium antagonists, which are mostly dihydropyridines. The longer half-life and physicochemical properties of some of the newer agents allow full 24-h blood pressure control. Duration of action of lacidipine: Taken only once a day, lacidipine has proved as potent an antihypertensive agent as slow-release nifedipine administered twice a day. Lacidipine produces a satisfactory fall in blood pressure not only during waking hours but also during sleep at night, as shown by 24-h ambulatory monitoring. Moreover, this blood pressure fall is obtained without any reflex tachycardia or associated side effects. Compared with patients treated with placebo, systolic and mean arterial blood pressure variability (standard deviation) is reduced by lacidipine treatment. CONCLUSIONS: Control of blood pressure using lacidipine once a day meets the criteria proposed by the United States Food and Drugs Administration for antihypertensive drug efficacy and duration of action. PMID- 8483018 TI - Comparative effects of antihypertensive drugs on systolic blood pressure. AB - Importance of systolic over diastolic blood pressure measurements: Systolic pressure is known to be a more important independent cardiovascular risk factor than diastolic pressure in subjects over 50 years of age; after that age, a high incidence of two types of systolic hypertension is observed, sustained essential hypertension with a disproportionate increase in systolic pressure and isolated systolic hypertension. Effects of lacidipine on blood pressure in the elderly: The effects of vasodilators on blood pressure have been studied extensively. Recently, lacidipine, nitrendipine and enalapril were compared in a multicenter, randomly allocated, double-blind trial in elderly hypertensive patients with a disproportionate increase in systolic pressure treated for 8 weeks (n = 278). In these patients, supine systolic pressure decreased to a greater extent with lacidipine and enalapril than with nitrendipine, the difference between lacidipine and nitrendipine reaching statistical significance. In another trial, lisinopril produced a greater reduction in systolic pressure than atenolol. Finally, in a study in elderly patients with systolic hypertension, long-acting isosorbide dinitrate induced a selective sustained decrease in systolic pressure. Mechanisms of action of vasodilators: A fall in systolic blood pressure may be produced by vasodilators through a reduction in peripheral resistance with or without an active change in arterial compliance. Dihydralazine-like substances do not increase arterial compliance whereas angiotensin converting enzyme inhibitors, calcium entry blockers and nitrates tend to increase arterial compliance for the same decrease in mean arterial pressure. PMID- 8483019 TI - Similarities and differences between calcium antagonists: pharmacological aspects. AB - Characteristics of three different calcium antagonist groups: Most important calcium antagonists used to treat cardiovascular disease belong to one of three main groups, phenylalkylamines, dihydropyridines and benzothiazepines. The best known drug in each group is verapamil, nifedipine and diltiazem, respectively. Dihydropyridines are predominantly vasodilators, with little or no primary cardiac activity; the tachycardia caused by these compounds is a reflex phenomenon. Verapamil and related drugs are also vasodilators, with an additional depressant effect on atrioventricular conduction, heart rate and contractility. Diltiazem's pharmacodynamic profile and side effects may be considered as intermediate between those of the dihydropyridines and verapamil. Characteristics of new calcium antagonists: Several new calcium antagonists have been introduced in the last few years, virtually all dihydropyridines. Compared with the older generation of calcium antagonists these newer drugs tend to have (1) a longer duration of action; (2) some selectivity for a specific vascular bed, such as resistance, coronary, renal or cerebral vessels; (3) a potentially useful extra component, such as diuretic or anti-atherogenic activity. Newer calcium antagonists described in this review: The newer compounds briefly characterized in this review are amlodipine, felodipine, isradipine, lacidipine, nimodipine, nisoldipine and nitrendipine. New slow-release formulations are also discussed. There is a particular emphasis on lacidipine and its potential for cardiovascular drug therapy. PMID- 8483020 TI - Effects of calcium antagonists on left ventricular structure and function. AB - Effects of calcium antagonists on left ventricular hypertrophy: The goals of antihypertensive treatment are to lower systemic blood pressure and to reverse left ventricular hypertrophy. A number of different drugs can induce a decrease in left ventricular mass, some of which are calcium antagonists. In particular, verapamil, diltiazem and a number of dihydropyridines (nifedipine, isradipine, lacidipine) have proved effective in this respect. Left ventricular systolic function: Left ventricular systolic function is often normal at rest in patients with hypertension, but is quite commonly abnormal during exercise. Calcium antagonists therefore do not affect resting systolic function in this category of hypertensive patients. In contrast, in hypertensive patients with heart failure the administration of dihydropyridines improves systolic performance. Left ventricular diastolic function: Isovolumic relaxation and rapid filling are often impaired in patients with hypertension, with or without left ventricular hypertrophy. Verapamil is effective in abolishing this diastolic dysfunction when given intravenously; in contrast, medium-term therapy with calcium antagonists such as diltiazem or dihydropyridines does not improve left ventricular filling properties. However, when antihypertensive therapy achieves a reduction in left ventricular mass, a consistent improvement in diastolic properties occurs. PMID- 8483021 TI - Vascular effects of lacidipine: a review of animal and human data. AB - AIM: To compare the vascular effects of lacidipine with those of other calcium antagonists. METHODS: A review of published studies. RESULTS: Experimental studies have shown that for a similar fall in blood pressure, lacidipine increased cardiac contractility while verapamil decreased cardiac contractility. In the rat aorta, the dose of lacidipine required to reduce a calcium-induced contraction by 50% was lower than that of all other calcium antagonists tested except nisoldipine. In human studies, especially, there are inherent limitations in the techniques available to measure regional blood flows under physiological conditions, making it difficult to compare the effects of different antihypertensive drugs. A recent study showed that renal blood flow was increased by lacidipine without any reduction in renal function. As in animals, vital organ perfusion was either preserved or increased. Further, maximal coronary vasodilation was associated with lower coronary resistance values during lacidipine treatment compared with pretreatment values. Another lacidipine study showed increased brachial artery compliance, while a study on the radial artery showed that lacidipine increased the compliance of this artery also. CONCLUSIONS: Lacidipine has vascular selectivity. Although regional blood flows are difficult to measure, due to inherent limitations in the techniques available, the evidence suggests that lacidipine produces vasodilation in essential hypertensive subjects while maintaining or even increasing vital organ perfusion. This appears to be due to a regression of the structural changes that characterize hypertension. PMID- 8483022 TI - Are there differences in the renal effects of calcium antagonists? AB - AIM: To review the effects of calcium antagonists, and of the new dihydropyridine lacidipine in particular, on the glomerular filtration rate, renal plasma flow, and the sodium to water ratio in hypertensive patients. METHODS: Review of published data. RESULTS: Different studies have shown a wide range of responses to all three subgroups of calcium antagonists in glomerular filtration rates and in renal plasma flows. In some studies there was a reduction and in others a rise in these two renal parameters. The administration of lacidipine was associated with a significant rise in renal plasma flow which disappeared with chronic treatment and no change in the glomerular filtration rate. There are only a few studies on the long-term natriuretic and diuretic effects of calcium antagonists. In the short term, dihydropyridine calcium antagonists appear to produce diuretic and natriuretic effects, but these effects are not seen with verapamil. Lacidipine showed no trend towards sodium and water retention. CONCLUSIONS: Reported differences between calcium antagonists in glomerular filtration and renal plasma flow probably reflect differences in the baseline tone of pre- and postglomerular arterioles. Calcium antagonists do not cause sodium and water retention during chronic therapy. The new dihydropyridine derivative lacidipine lowers blood pressure without reducing renal function or causing sodium and water retention. PMID- 8483023 TI - Calcium antagonists and renal protection. AB - AIM: To review the renal benefits of calcium antagonists. METHODS: Review of published studies. RESULTS: Both experimental and clinical studies have indicated that, apart from being highly potent antihypertensive agents, calcium antagonists may also provide tissue protection and preservation. In three well defined clinical situations, the use of calcium antagonists has proved to be of value. First, in acute renal failure we and others have shown that the administration of dihydropyridine or diltiazem can, by preventing an intracellular calcium overload, avoid the renal damage induced by the use of a radiographic contrast agent. Second, in chronic renal failure, the administration of a calcium antagonist has been shown to be safe and at least similar in efficacy to other commonly used antihypertensive drug classes. Third, in renal transplant patients, calcium antagonists have been shown to prevent both acute and chronic cyclosporin nephrotoxicity. Calcium antagonists have a clear advantage in the case of acute toxicity because they allow faster renal function recovery and a shorter hospitalization time. The mechanisms by which this class reduces cyclosporin toxicity may be related to a reduction in the calcium influx into cells during ischaemic and reperfusion periods, which would reduce the generation of oxygen free radicals and perhaps reduce thromboxane production. CONCLUSIONS: Calcium antagonists have potential renal protective effects that favour their use in many clinical situations where renal function is impaired. PMID- 8483024 TI - Anti-atherosclerotic effects of calcium antagonists. AB - Effects of calcium antagonists on atherosclerosis in experimental animals: A variety of calcium antagonists can inhibit the development of aortic atherosclerosis induced by marked hypercholesterolemia in cholesterol-fed animals, following mechanical injury or intoxication with vitamin D, but not in the heritable hyperlipidemic rabbit. This effect is not mediated by modifications to plasma lipids, blood pressure or other conventional risk factors. Effects of calcium antagonists on atherosclerosis in humans: It has been difficult to assess the effects of calcium antagonists on the atherogenetic process in humans. Studies on the action of calcium antagonists in the primary prevention of atherosclerosis are obviously desirable; however, they are almost impossible to perform due to the slow development of atherosclerosis and the need for long-term follow-up. Data from several clinical trials in patients with established coronary artery disease have indicated that calcium antagonists may prevent the development of new atherosclerotic plaques and may even slow the progression of established lesions. CONCLUSIONS: Present experimental and clinical evidence indicates that calcium antagonists may be able to prevent or retard the progression of atherosclerosis by mechanisms independent of and in addition to blood pressure reduction. Large long-term trials are needed to confirm this finding and to determine whether the effect is associated with a decrease in atherosclerotic morbid and fatal complications. PMID- 8483025 TI - Effects of lacidipine on experimental models of atherosclerosis. AB - AIM: To evaluate the effect of lacidipine on the major processes of atherogenesis. METHODS: Cell-culture methods were used to study the effect of lacidipine. Low-density lipoprotein (LDL) receptor expression and cholesterol esterification were evaluated in human skin fibroblasts and in mouse peritoneal macrophages, respectively. The effect of lacidipine on cellular proliferation was tested on aortic myocytes cultured from rat aorta. RESULTS: Lacidipine did not affect LDL receptor expression, but it inhibited the ability of acetyl LDL to stimulate cholesterol esterification in macrophages by more than 95%. The drug inhibited cellular proliferation in a dose-dependent manner. This antiproliferative effect was confirmed in human femoral artery myocytes. In accord with the inhibitory effect on cellular growth, preliminary in vivo studies suggest that lacidipine may reduce neointimal formation induced by perivascular manipulation of the carotid artery in hypercholesterolemic rabbit. CONCLUSIONS: Our results indicate that lacidipine may be antiatherosclerotic through an effect on the major processes involved in atheroma formation. PMID- 8483026 TI - Clinical experience with HIV-infected patients at the University of Oklahoma Health Sciences Center: an update. AB - We reviewed the course of 545 human immunodeficiency virus (HIV)-infected patients seen between 1983 and March 30, 1991. A majority were Caucasian homosexual or bisexual men, while parenteral drug abusers represented a smaller proportion than seen nationwide. In the 274 patients with the acquired immunodeficiency syndrome (AIDS), the distribution of AIDS-defining conditions was generally consistent with those reported in studies from elsewhere in the United States. However, toxoplasmosis remained relatively uncommon. There was a slightly higher incidence of disseminated histoplasmosis compared to other studies. HIV encephalopathy (AIDS dementia) was likely underdiagnosed. Although data suggested prolongation of the asymptomatic phase of HIV infection, median survival after AIDS diagnosis remained approximately 12 months. PMID- 8483027 TI - The misuse of cardiopulmonary resuscitation. AB - Over a 41-month period, 1,233 "Code Blues" were retrospectively reviewed. Twenty five codes on infants and children < 16 years of age were eliminated from the study group. The adult survivors of 1,208 codes numbered 243 (20.1%). Clinical chart review revealed that 49 (4.0%) did not involve cardiopulmonary resuscitation (CPR) or intubation and were "non-codes." Of the remaining 1,159 codes, there were 194 (16.7%) survivors. Of these survivors, 102 (52.5%) were patients with respiratory distress or failure and required intubation only. No CPR was needed. Thus, only the remaining 92 survivors of the 1,057 codes were cardiac cases for which CPR was appropriate (8.7% survival). Ventricular tachycardia and fibrillation, promptly defibrillated, was the most important rhythm factor for survival. Underlying ischemic heart disease (acute myocardial infarction and chronic ischemic heart disease with arrhythmia) was the most common underlying disease entity among the survivors. CPR performed in the group of patients unlikely to survive was expensive. PMID- 8483028 TI - Firearm-related mortality in Oklahoma, 1985-1989. AB - To determine the extent of firearms as a cause of mortality, Oklahoma vital statistic records were analyzed. The annual mortality rate in Oklahoma between 1985 and 1989 was 20% higher than the U.S. rate. Firearms were the second leading cause of injury deaths; firearms were the leading cause of injury deaths among blacks and the leading cause of all deaths among blacks 15 to 29 years of age. Ninety-two percent of the firearm-related deaths were intentional; firearms accounted for 70% of suicides and 59% of homicides. The male death rate from firearms was 4.5 times the female death rate. Suicide rates were highest among white males 65 years and older; homicide rates peaked among black males 25 to 34 years of age. Residents of eastern Oklahoma had the highest rates. The magnitude and preventability of firearm-related deaths and injuries demand attention and collaboration from Oklahoma health care providers; public health, mental health, and education officials; and criminal justice professionals. PMID- 8483029 TI - In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage. AB - Naproxen is a nonsteroidal anti-inflammatory drug commonly used in the clinical treatment of joint disease. In this study, its effect in vivo on the biochemical composition, metabolic activities, and metalloproteinase activities of normal canine articular cartilage was analyzed. The articular cartilage from the knee joints of dogs who had been given naproxen for 4 weeks to maintain a serum level of 40-50 micrograms/ml was examined. Control animals were given a placebo. Treatment with naproxen was not found to change the composition (water, collagen, and proteoglycan) of the articular cartilage. The culture studies of cartilage explants indicated that proteoglycan synthesis rates were unaffected by the treatment with naproxen but that proteoglycan release from the tissue was suppressed. Analysis of the cartilage for matrix metalloproteinase activities showed reduced activity of neutral matrix metalloproteinase by 80%, of collagenase by 40%, and of gelatinase by 87%, with no change in activity of acid metalloproteinase or of tissue inhibitor for metalloproteinase. These findings indicate that in vivo treatment with naproxen has the capacity to modulate catabolic activities in articular cartilage. PMID- 8483030 TI - Functional assessment of joint use in experimental inflammatory murine arthritis. AB - A select group of cartilage proteoglycans (fetal human, porcine, and canine articular cartilages and human osteophytes, all depleted of chondroitin sulfate) produces progressive polyarthritis and spondylitis in BALB/c mice. The development of the disease in this murine strain is dependent on the expression of both cell-mediated and humoral immunities to host mouse cartilage proteoglycan. Autoantibodies have been detected in sera of arthritis animals from the fifth to sixth week after immunization, and their appearance precedes the development of the first clinical symptoms by a few days in animals with passively transferred arthritis. In this preliminary experiment, we describe several functional tests and gait analyses in normal mice, in acutely and chronically arthritic mice, and in randomly selected mice with proteoglycan induced and collagen-induced arthritis. The procedures revealed that changes in joint use and gait could predate by weeks the appearance of the first clinical symptoms (joint swelling, redness, and joint stiffness) of arthritis in mice. Moreover, abnormalities measured by functional tests, such as strength of grip and maintenance of posture on sandpaper, wood, or vinyl surfaces at three different tilt angles (30, 45, and 60 degrees), and gait analysis preceded the appearance of autoantibodies in sera of immunized animals; this indicates that such measurements could provide a noninvasive and simple method to assess joint function accurately during the development of arthritis. PMID- 8483031 TI - Effects of solvent preservation with or without gamma irradiation on the material properties of canine tendon allografts. AB - We studied the effects of solvent preservation with and without gamma irradiation on the material properties and morphology of canine tendons. Twenty-four paired tendons were harvested from both hind limbs of eight dogs. The tendons from the right legs were divided into three treatment groups of eight tendons each. In the first group, the tendons were subjected to solvent preservation for sterilization and drying (solvent group). In the second group, the tendons were treated in the same manner and then were sterilized by gamma irradiation (solvent/gamma group). The same treatments were applied to the tendons in the third group but in reverse order (gamma/solvent group). Tendons from the contralateral left legs were frozen immediately for use as controls for each corresponding treatment group. Histologically, the tendons treated with solvent, with or without gamma irradiation, had a more prominent wavy pattern in the collagen fibers than the control tendons. Mechanically, the tangent moduli for the solvent, solvent/gamma, and gamma/solvent groups were 58, 53, and 99%, respectively, of each contralateral control. The respective tensile strengths were 85, 39, and 86% of that of the contralateral control. The tendons in the solvent/gamma group underwent the most severe changes in material properties; the tendons in the gamma/solvent group changed the least. This suggests that gamma irradiation followed by solvent drying is the procedure of choice for the preservation of tendon allografts. PMID- 8483032 TI - Dynamic elongation behavior in the medial collateral and anterior cruciate ligaments during lateral impact loading. AB - The objectives of this experimental study were to determine (a) how quickly the medial collateral ligament (MCL) and the anterior cruciate ligament (ACL) elongate when a lateral impact force is imparted to the knee and if a person can react rapidly enough to provide protective muscle forces in the case of such an impact, (b) if the MCL and the ACL elongate simultaneously during a lateral impact, and (c) if resection of the ACL affects elongation of the MCL during a lateral impact. Eight whole-leg cadaver specimens were used. Each leg was mounted vertically in a testing-frame with the knee in 0 and 30 degrees of flexion. A submaximal impact was delivered from the lateral side by a pendulum instrumented with a force transducer. Elongation of the midsubstance of the MCL and the ACL was measured with Hall-effect displacement transducers. The ACL was resected and the entire test sequence was repeated. Following a lateral impact, elongation of the MCL and ACL reached peak values by 70 ms. This study indicated that contraction of the leg musculature would not protect the MCL and ACL from injury when a lateral impact load is applied to the knee. The MCL and the ACL never elongated simultaneously during a lateral impact. After lateral impact loading, the time required to reach maximum elongation (peak delay) averaged 52 ms in the anterior MCL fibers and 61 ms in the ACL when the knee was in 0 degrees of flexion. At 30 degrees of flexion, the peak delay averaged 38 ms in the anterior MCL fibers and 22 ms in the ACL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483033 TI - The Maquet procedure: effect of tibial shingle length on patellofemoral pressures. AB - The Maquet procedure--elevation of the anterior tibial tubercle--has been recommended for treatment of symptomatic osteoarthrosis of the patellofemoral joint. Although the operation was first described 30 years ago, it remains controversial, both on a clinical and on a biomechanical basis. In addition, deterioration of the long-term results has been suggested. One of the variables that has been ignored in both clinical and biomechanical studies has been tibial shingle length. In order to judge its effect, we examined contact pressures and areas in 15 cadaver knees with 7 and 20 cm tibial shingle lengths. We found significant patellofemoral pressure diminution only with 2 cm elevations. The short anterior tibial shingle with 2 cm of elevation tipped the patella on its superior pole, with a significant change in angle between the patella and the shingle. We suggest that this creates a potentially less than desirable biomechanical circumstance and believe it may explain the discrepancies among previously published reports. PMID- 8483034 TI - Complex balance reactions in different sensory conditions: adolescents with and without idiopathic scoliosis. AB - We measured simple and complex balance responses with a force plate stabiliometer in 70 adolescents: 50 with idiopathic scoliosis (IS) and 20 controls. In stable static balance positions, the two groups performed similarly, but when the visual and somatosensory systems were challenged simultaneously, the IS group had a significantly higher mean body sway than the controls. Within the IS group, children with mild, nonprogressive curves that had not been operated on were significantly more likely to maintain their balance when the visual and somatosensory systems were challenged simultaneously than those with curves > or = 40 degrees, who had had surgery, and who had more rapid progression of the curve. These findings suggest that adolescents with IS have normal balance in static, stable positions but are not able to perform as well as normal adolescents in sensory-challenged positions, particularly if they have a severe, progressive curve. Longitudinal studies are needed to determine whether balance dysfunction can be used to predict progression of the curve. PMID- 8483035 TI - Compressive properties of the cartilaginous end-plate of the baboon lumbar spine. AB - The viscoelastic behavior of the cartilaginous end-plate of the baboon (Papio anubis) was studied in an experiment on compressive creep. Data were analyzed with the biphasic poroviscoelastic constitutive theory to assess the relative contributions of flow-dependent and flow-independent viscoelastic mechanisms to the observed creep behavior. Material coefficients describing the equilibrium compressive behavior (HA) and both flow-independent (c, tau 1, and tau 2) and flow-dependent (k) viscoelastic effects were determined for the end-plate by the curve-fitting of the theoretical solution to the experimental creep data. Biochemical analyses were performed to test for potential relationships between material properties and composition which may give rise to the viscoelastic behavior of the end-plate. The results indicate that the cartilaginous end-plate has a hydraulic permeability of 14.3 x 10(-14) m4/N-s, which is associated with rapid transport and pressurization of the interstitial fluid in response to loading and an increased emphasis on flow-independent viscoelastic effects. Biochemical analyses for water, sulfated glycosaminoglycan content, and hydroxyproline indicate that the end-plate of the baboon is compositionally similar to the cartilaginous end-plate in humans. Interpretation of the mechanical and compositional data suggests that fluid pressurization in the cartilaginous end-plate may be important in the maintenance of a uniform stress distribution across the boundary between vertebral body and intervertebral disc. PMID- 8483036 TI - The effects of cisplatin on the incorporation of fresh syngeneic and frozen allogeneic cortical bone grafts. AB - Allograft transplantation with concomitant chemotherapy has proven successful in the treatment of malignant bone tumors. However, these chemotherapeutic agents may delay tissue healing, resulting in clinical complications. To clarify the effects of cisplatin on the healing of bone grafts, we studied the incorporation of stably fixed massive diaphyseal femoral syngeneic and allogeneic grafts in rats treated with cisplatin. These data were compared with those of historical controls from animals that did not receive cisplatin. Rats that were to receive a fresh syngeneic graft or frozen allogeneic graft were given cisplatin every 4 weeks starting 9 weeks preoperatively and continuing until the time of death. The total bone area of the graft in animals that received cisplatin was smaller than that of the graft in untreated control rats that did not receive cisplatin. The area of the frozen allograft did not increase between 2 and 4 months. Revascularization was incomplete in cisplatin-treated groups at 2 months, but by 4 months, vessel ingrowth in fresh syngeneic grafts approached control values. Frozen allografts remained poorly revascularized at 4 months. Host-graft union was poor at 2 months in cisplatin-treated rats compared with controls. In cisplatin-treated rats, the host-graft union of the frozen allograft remained inferior at 4 months while that of the syngeneic graft improved. Allogeneic cortical bone grafts are incorporated more slowly and incompletely than syngeneic grafts, and this handicap is exacerbated by the administration of cisplatin. PMID- 8483037 TI - Antibiotic-loaded biodegradable bone cement for prophylaxis and treatment of experimental osteomyelitis in rats. AB - A biodegradable, particulate composite bone cement containing gentamicin and vancomycin was used for both treatment and prophylaxis of Staphylococcus aureus osteomyelitis in rats. Osteomyelitis was established by inoculating S. aureus into holes that were drilled in the proximal tibiae and were filled with polymethylmethacrylate (PMMA) cylinders. The cylinders were left in place for 3 weeks. The infections were serially evaluated by clinical and radiographic examination and by quantitative culture for colony forming units (CFUs) at the time the rats were killed. For treatment, cements containing antibiotic were implanted in animals that had established osteomyelitis and were left in place for an additional 3 weeks. Sites treated with biodegradable cement containing antibiotics exhibited significantly fewer CFUs in comparison with controls (p < 0.01). Sites treated prophylactically with the biodegradable cement developed no infections as evaluated by clinical or radiographic criteria or by quantitative culture. At this relatively early time, no significant difference in therapeutic effectiveness was found when either the biodegradable cement or PMMA was used as a carrier for antibiotics. PMID- 8483038 TI - Bioerodible polyanhydrides for antibiotic drug delivery: in vivo osteomyelitis treatment in a rat model system. AB - Acute and chronic osteomyelitis can be difficult to treat by conventional means. Current methods of treatment involve the use of systemic antibiotics, the local implantation of non-degradable drug carriers, and surgical debridement. Each method has specific drawbacks. We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolymers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague-Dawley rats infected with a strain of Staphylococcus aureus. After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period. Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p < 0.01), of animals with a polyanhydride polymer implant alone (p < 0.01), and of animals with a PMMA/gentamicin implant (p = 0.03). Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone. PMID- 8483039 TI - Effects of severe diabetes and insulin on the femoral neck of the immature rat. AB - The interactive effects of severe diabetes and insulin therapy on the geometrical, biomechanical, and histomorphological characteristics of the femoral neck were studied in rats that had streptozotocin-induced, insulin-dependent (Type-I) diabetes. Thirty-six female Sprague-Dawley rats (8 weeks of age) were assigned randomly to one of three groups: 12 to control (C), 12 to severe diabetes mellitus (SDM), and 12 to severe diabetes with insulin treatment (SDI). At the conclusion of 10 weeks, the femoral necks were loaded to failure via cantilever-bending tests, and the geometrical, structural, and material properties of the femoral neck were measured and correlated with fracture-surface cross sections. Decalcified cross sections of the femoral necks were analyzed histomorphometrically to determine the porosity, the bone-cell counts, and the bone spicule/marrow space ratio. Rats with severe insulin-dependent diabetes had significantly lower total body mass than did control rats, as well as significantly less femur mass, femur length, total-bone cross-sectional area, and cortical-shell cross-sectional area. Insulin therapy ameliorated some, but not all, of the detrimental effects of diabetes on femoral neck geometry. Compared with control and SDI rats, SDM rats had lower values for femoral neck structural properties, although differences in structural properties may have been related to retarded growth as well as to diabetes. SDM rats had a significantly lower bone spicule/marrow space ratio and number of osteoclasts than did either the control or SDI rats and had significantly greater porosity in the femoral neck cortex than did control rats. Decrements in femoral neck material properties- which were independent of differences in body size--were significantly and linearly correlated with severity of diabetes (as measured by blood glucose level). PMID- 8483040 TI - Load transfer with the Austin Moore cementless hip prosthesis. AB - More than 1,300 Austin Moore hemiarthroplasties have been reviewed in the literature, with no reports of fracture of the stem. Many patients with these hip implants had good function. The lack of stem fractures in patients with good functions has not been explained and contrasts with stem fractures that have occurred in patients with cemented prostheses of other designs during the same time. We used three-dimensional finite-element analysis and free-body diagrams to explain the lack of fractures for this device by a description of the probable load-transfer mechanisms between the prosthesis and the bone. Results from our finite-element analysis indicate that, with good calcar-collar support, the stresses in the stem are small because the stem portion of the prosthesis and the bone are uncoupled and, consequently, do not share the resultant bending moment of the head and abductor forces. If the stem is coupled to the bone so that the resultant bending moment is shared, high stresses in the stem are predicted; such stresses are inconsistent with the complete absence of fractures of these prostheses. The results of the finite-element analysis further showed that loss of calcar-collar support with proximal fixation through the fenestrations resulted in high stresses in the stem and stress shielding of the proximal medial cortex. The uncoupled prosthesis also may be modeled with a free-body diagram as a three-force member loaded at the head, stem tip, and in the proximal region. With this model, it can be shown that the reaction force of the stem tip, and thus the peak bending stress in the stem, increases as calcar-collar support is decreased. If there is no calcar-collar support, proximal support must be provided by some combination of integration of bone in the fenestrations and wedging due to the lateral-medial taper of the device. Stresses in the stem are largest when there is no wedging, but high stresses develop in the cancellous bone in the fenestrations. When there is wedging, stresses in the stem can be low, but stresses in the supporting cancellous bone can be high; additional proximal support through the fenestrations substantially reduces these bone stresses. If reduced stresses in the cancellous bone are indicative of a stable device, these mechanisms indicate that fractures of the Austin Moore prosthesis have not occurred in normally loaded hips because load was transferred primarily either through the collar or by wedging, with additional support at the fenestrations. PMID- 8483041 TI - Healing of cancellous bone osteotomy in rabbits--Part I: Regulation of bone volume and the regional acceleratory phenomenon in normal bone. AB - We performed a simple, undisplaced, incomplete osteotomy of the distal medial condyle of mature New Zealand White rabbits and permitted healing without fixation for 4 weeks. During the recovery period, the rabbits received the bone label calcein in their drinking water. From ground stained and unstained sections, we determined histomorphometric parameters in five zones: osteotomy gap, juxtaosteotomy, lateral condyle, metaphysis, and diaphysis. At 4 weeks, newly formed cancellous bone had obliterated the osteotomy gap. Osteotomy also stimulated new bone formation in cancellous bone of the medial condyle around the osteotomy. At that site, we found a fivefold increase in new bone without a change in bone volume (BV). Stimulation of bone formation was not observed in cancellous bone of the lateral condyle that had not been operated on or in cortical bone of the metaphysis or diaphysis. The maintenance of BV, despite increased new bone formation in the osteotomized medial femoral condyle, was probably due to a local acceleration of bone remodeling. PMID- 8483042 TI - Healing of cancellous bone osteotomy in rabbits--Part II: Local reversal of arthritis-induced osteopenia after osteotomy. AB - With use of the intravital bone label calcein, we previously identified, by histomorphometry, greatly increased new bone formation and juxtaarticular osteopenia (a high turnover state) in carrageenan-induced experimental inflammatory arthritis of the knee in rabbits. In Part I of this paper, we showed that a large increase in new bone formation after a stable incomplete distal femoral condylar osteotomy of normal bone in the rabbit does not increase bone volume (BV) in normal tissue adjacent to the osteotomy (zone 1). In this study, we performed an osteotomy of bone made osteopenic by experimental inflammatory arthritis. After 4 weeks of healing, we examined new bone formation and BV in five zones around the osteotomy. In zone 0 (the osteotomy gap), new bone formation filled the gap to normal BV, as we found for the normal/osteotomy group. In zone 1 (adjacent to but excluding the osteotomy gap), we found greatly increased new bone formation and a return to normal BV, increased from the osteopenic level induced by experimental inflammatory arthritis. In this model, osteotomy apparently reversed the bone-wasting process of inflammatory arthritis. This effect was not observed in other zones: the lateral condyle that had not been operated on, the metaphysis, or the diaphysis. PMID- 8483043 TI - Muscle contraction increases the structural capacity of the lower leg: an in vivo study in the rat. AB - A model to study the contribution of muscle contraction to the structural capacity of the rat tibia was developed. The right lower leg was tested to failure in three-point ventral bending during electrically stimulated muscle contraction. The left lower leg was tested without stimulation, as a control. The mean ultimate bending moment for the stimulated legs was 0.603 Nm, compared with 0.492 Nm for the unstimulated legs (p < 0.001). The ultimate energy absorption was 0.313 and 0.188 J in the stimulated and unstimulated legs, respectively (p < 0.01). Fracture strength has been studied nearly exclusively in dissected bone stripped of all soft tissues. The present investigation suggests that studies of dissected bone are incomplete compared with the in vivo situation, as contraction of the muscles substantially increased the fracture strength of the lower leg in rats. PMID- 8483044 TI - A standardized experimental fracture in the mouse tibia. AB - The increased use of transgenic mice as experimental animals provides new opportunities to study the biology of fracture repair. We have developed a technique for the production of a standard closed experimental fracture in the mouse tibia. A 0.2 mm stainless-steel rod was introduced into the medullary cavity and the pre-nailed tibial shaft was fractured by an impact device, which resulted in a reproducible transverse or slightly oblique fracture pattern. The intramedullary rod maintained axial alignment, and the fractures united without displacement. On the basis of measurements of callus geometry, four-point bending tests, biochemical analyses, and quantitative histology, the progress of callus formation and remodeling occurred in a predictable sequence of healing phases. The ultimate bending loads of the fractures increased with time, reaching 74% of the strength of intact control tibias in 4 weeks. The stiffness values of the fractures returned to normal levels and, as determined radiographically, the fractures united by external callus in 4 weeks. Radiographically, callus size, cross-sectional callus area, and callus mass peaked at 2 weeks and decreased thereafter, indicating the start of external remodeling. Histologically, the amount of mesenchymal tissue was maximal at days 5 and 7. The callus cartilage area peaked at day 9; at its maximum, it accounted for 46% of the total callus area. Early periosteal formation of membranous new bone, followed by endochondral ossification, resulted in a linear increase of callus bone during the healing process. The healing sequence of the mouse tibial fracture was similar to that seen in the rat tibia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483045 TI - African-centered drug treatment: an alternative conceptual paradigm for drug counseling with African-American clients. AB - An alternative conceptual framework is presented for understanding the culturally normative behavior of African-Americans in drug abuse treatment and recovery, based on an appreciation of core African-centered beliefs. Key ontological and epistemological assumptions of traditional clinical and counseling interventions are presented that highlight the differences between traditional goals and theories and the proposed alternative conceptual system and treatment strategies. Implications for African-centered treatment and future research on the course of addiction and recovery among African-Americans are discussed. PMID- 8483046 TI - Enrollment of drug abusers in HIV clinical trials: a public health imperative for communities of color. AB - There is an increasing appreciation of the impact of drug abuse on AIDS in the United States because of the pivotal role of injecting drug use in the prevalence of total AIDS cases and case reporting among ethnic/racial minorities, women, and children. While the participation of injecting drug users (IDUs) in HIV clinical trails has increased steadily, the IDU accrual rate lags unacceptably behind the IDU proportion of AIDS cases. The stigma of drug abuse, issues related to poverty, and the underrepresentation of communities of color are the major obstacles to IDU participation in HIV clinical research. It is critical to overcome these obstacles as the spectrum of HIV disease in IDUs requires the development of an IDU-relevant scientific agenda for HIV clinical trials. This, in turn, is crucial to the development of effective therapies for the treatment of HIV disease in IDUs. To the extent that these endeavors are successful, more relevant therapies to communities of color will be developed, as injecting drug use is disproportionately more prevalent in these communities. PMID- 8483047 TI - Cultural competence: an interview with Warren Hewitt. Special Assistant to the Director, Center for Substance Abuse Treatment. PMID- 8483048 TI - Priorities for alcohol treatment research among U.S. Hispanics. AB - This article reviews the clinical research conducted with U.S. Hispanics and discusses priorities for alcohol treatment research in this ethnic group. Specific areas in which research is needed include epidemiological descriptions of client characteristics, access and utilization of alcohol treatment, the structure of alcohol programs, pathways to treatment, alcohol dependence and treatment effectiveness, and treatment matching in alcohol treatment. Methodological requirements, research funding strategies, and professional training needed for implementing the research needs identified in the article are also discussed. A concerted effort by funding institutions is needed to emphasize the importance of this research, and an increased commitment of funds for research and professional training is necessary. Such funds should be earmarked for research with minorities and training for minority professionals. PMID- 8483049 TI - Substance abuse treatment: cultural barriers in the Asian-American community. AB - Asians constitute the largest growing minority in the United States. However, inaccurate perceptions and stereotypes continue to mask a full understanding of the state of knowledge regarding their alcohol and other drug abuse. Much of the existing research has continued this trend by categorizing Asians as "others" or persisting in its attempts to explain low incidence rates by investigating metabolic phenomena. More recent community-based studies have shown alarming incidence rates of specific substance abuse among different Asian ethnic groups. Asian heterogeneity and cultural barriers have also contributed to the lack of knowledge regarding substance abuse prevalence rates. Issues related to taboo, denial, and loss of face further mask understanding of the extent of the problem. Institutional barriers and the lack of community infrastructure make treatment efforts difficult in serving a myriad of Asian groups. For most Asians undergoing treatment, cultural factors need to be considered, including the involvement of the family as well as the risk related to its transition under immigration and the following acculturation patterns. An example of a specific treatment program and activity is discussed in relationship to the cultural factors indicated above. Finally, recommendations are specified for future treatment policy, research, and services. PMID- 8483050 TI - Addressing treatment needs of Southeast Asian Mien opium users in California. AB - This report describes efforts in progress to meet the needs of opium smoking Mien immigrants in Oakland, California. Translating concepts of addiction and recovery into terms that are culturally relevant constitutes the basis for efforts to assist the Mien to adjust to an opium-free lifestyle. The acceptability and utility of clonidine, acupuncture, methadone, counseling, support groups, and other medical services are discussed. PMID- 8483051 TI - Is the therapeutic community culturally relevant? Findings on race/ethnic differences in retention in treatment. AB - The therapeutic community (TC) views cultural diversity as an essential ingredient in its treatment approach. However, based on clinical observation and some research, questions persist concerning the relevance of TC programming for numerical race/ethnic minorities. This article briefly reviews pertinent research and presents findings from recent studies on race/ethnic differences in readiness and suitability for, and retention in, TC treatment. A framework is outlined for the empirical study of cultural relevance issues in TCs. PMID- 8483052 TI - International training for drug abuse treatment and the issue of cultural relevance. AB - During the last ten years, there has been an increased demand for culturally relevant drug abuse treatment that is responsive to the unique needs of international populations, each with its own special culture and taboos. This article explores the assumptions that these distinct cultural characteristics require different treatment approaches to be effective, and presents both curriculum content and training designs used in educating diverse cultures in drug abuse treatment strategies. The authors discuss their training experiences in Central Europe, the Mediterranean, China, and Southeast Asian countries and conclude that, while cultural uniqueness certainly exists, it may be greatly exaggerated in terms of the need for special treatment modalities in the field of drug abuse treatment. PMID- 8483053 TI - Cross-cultural counseling with the chemically dependent: preparing for service delivery within a culture of violence. AB - This article prepares the clinician delivering chemical dependency treatment for more effective work in therapeutic dyads where there are racial, ethnic, or other "differences" between client and therapist. The objective is to prepare clinicians for service delivery within the present culture of violence and for the receipt of additional training in cross-cultural counseling and trauma resolution psychotherapy. Social learning and unconscious processes are reviewed in order to explain how this culture of violence operates and impacts treatment. The way in which chemically dependent clients of color--especially African Americans, Native Americans, and Latinos--have been impacted by both personal and cultural trauma is illustrated by a case example. The resolution of clients' personal trauma by properly trained clinicians is presented as relapse prevention and the clients' best defense against becoming a victim of violence and racism. The article ends with a brief description of the recommended clinical technique for this kind of work, and a statement of needed research. PMID- 8483054 TI - Cultural points of resistance to the 12-Step recovery process. AB - This article addresses some of the key issues in developing culturally relevant approaches to drug abuse treatment and recovery, using the HAFC/Glide African American Extended Family Program as a positive example of effective cultural adaptability within recovery. Cultural points of resistance to the recovery process are also addressed, including the perception that 12-Step fellowships are exclusive and confused with religion, confusion over surrender versus powerlessness, and concerns about low self-esteem, dysfunctional family structure, communication difficulties, and institutionalized and internalized racism. The authors also focus on professional resistance in other countries, where different treatment approaches and philosophies block the acceptance of a recovery concept in general and the 12-Step process in particular. In explicating these issues, addiction is presented as a multicultural problem in need of multicultural solutions. The challenge is to adapt the process of recovery to all cultures and races, to counter stereotypes on all sides, and to eliminate the perception that recovery only works for addicts from the White mainstream. PMID- 8483055 TI - Characterization of two monoclonal antibodies against secretory proteinase of Candida tropicalis DSM 4238. AB - Two murine IgM monoclonal antibodies (mAb; MT1 and MT2), which were produced against the secretory aspartic proteinase of Candida tropicalis DSM 4238, are described. Both antibodies reacted with the native and denatured conformations of the homologous proteinase antigen but showed different patterns of reactivity with other related proteinases (Candida albicans CBS 2730, serotype A; C. albicans ATCC 48867, serotype B; Candida parapsilosis DSM 4237) and with porcine pepsin. Neither of the antibodies inhibited the proteolytic activity of the homologous enzyme. MT1 also reacted with mannoproteins of C. tropicalis DSM 4238 and C. albicans CBS 2730 and immunofluorescence revealed that this antibody bound to the surface of blastoconidia and pseudomycelia of these two Candida species. A reaction with blastoconidia only was observed with C. albicans serotype B. MT1 also reacted weakly with Candida guilliermondii, but not with C. parapsilosis, Candida glabrata, Candida krusei or Candida kefyr. MT2 did not bind to fungal surfaces. Preliminary experiments suggested that mAb MT1 may recognize a carbohydrate epitope, while MT2 binds to an epitope consisting of the protein part of the enzyme. The two antibodies were used in an ELISA for the detection of proteinase antigen. ELISA with MT1 or MT2 as coating antibodies and a specific protein epitope recognizing mAb-biotin conjugate was able to detect 4 ng ml-1 of antigen. Trials with 26 sera from fungemic patients and 14 sera from controls suggest that MT2 is of potential value in antigen-directed serodiagnosis. PMID- 8483056 TI - The role of the complement system in the neutrophil functions stimulated in vitro by an alkali-insoluble cell wall fraction of Paracoccidioides brasiliensis. AB - We investigated the capacity of an alkali-insoluble cell wall polysaccharide fraction (F1) of Paracoccidioides brasiliensis to induce rat polymorphonuclear neutrophil (PMN) migratory and chemiluminescence (CL) responses. Normal rat serum pre-incubated with F1 induced a chemotactic neutrophil response which was fully abolished by heat-inactivation. The participation of the alternative complement pathway was more effective than that of the classical pathway since depletion of factor B by heating at 50 degrees C reduced PMN migration, whereas blockade of the classical pathway with EGTA left the migratory response practically unchanged. Opsonized serum F1 induced a significant release of oxygen radicals from PMN as measured by CL. The complement system was also found to be involved in this activity since serum inactivation at 56 degrees C altered the CL response. In addition to complement-derived fragments, other serum opsonins, probably cross-reacting antibodies, were required for optimal interaction between PMN and opsonized particles. These results contribute to the understanding of the role of fungal components and of the complement system in the inflammatory response observed in paracoccidioidomycosis. PMID- 8483057 TI - Calcium stimulates molecular and cellular events during the yeast-to-mycelium transition in Sporothrix schenckii. AB - Calcium ions (Ca2+) have been identified as mediators of proliferative and morphogenetic processes in many eukaryotic cells. The effects of these ions on the cellular and macromolecular processes that accompany the dimorphic transition from the yeast-to-mycelial form of Sporothrix schenckii have been studied. Ca2+ were found to stimulate germ tube formation and growth in these cells at an optimal concentration of 1.0 mM. Studies concerning the effects of this cation on the molecular processes that precede germ tube formation revealed that the earliest molecular event which was stimulated by 1.0 mM Ca2+ was RNA synthesis. An increased incorporation of radioactivity into RNA in the presence of 1.0 mM Ca2+ was first observed at 0-3 h, and subsequently at all other times tested, following inoculation. A stimulation in rRNA and tRNA synthesis was detected in the presence of 1.0 mM Ca2+. The incorporation of radioactivity into proteins was stimulated 3-5 h following induction in the presence of Ca2+ suggesting a specific effect of Ca2+ on protein synthesis. This increased incorporation takes place prior to the start of DNA synthesis. Incorporation of radioactivity into DNA was also stimulated in the presence of Ca2+, 6 and 9 h after inoculation. This stimulation resulted in nuclear division taking place with a shorter lag period and proceeding with increased kinetics. The results reported here are evidence that Ca2+ plays a role in the control of the early molecular and cellular processes that accompany the yeast-to-mycelium transition in S. schenckii and offer an explanation of how Ca2+ can control the expression of the dimorphic potential of this fungus. PMID- 8483058 TI - Conditions affecting the adherence of Cryptococcus neoformans to rat glial and lung cells in vitro. AB - Conditions affecting the adherence of clinical isolates of Cryptococcus neoformans to rat glial and lung cell cultures were studied. Adherence to glial cells was a time-dependent process that was affected by the yeast culture age and growth temperature. The most adherent yeasts were those from 48 h cultures grown at 37 degrees C. Formalin-treating the yeasts did not affect adherence but formalin-treating the glial monolayers prevented yeast binding. Treating the yeasts with trypsin reduced adherence to glial monolayers, indicating that the yeast adhesin had a trypsin-labile protein component. Certain carbohydrates inhibited cryptococcal adherence to glial and lung cells in a time and concentration-dependent manner. Of the carbohydrates tested, N-acetyl-D glucosamine, sucrose, lactose, sorbitol and myo-inositol were the most inhibitory, while mannose, galactose and xylose were the least inhibitory. The results collectively indicated that the mechanisms of adherence of C. neoformans to lung cells were similar to those of glial cells and that both involved a protein-containing adhesin on the cryptococcal surface that was expressed only after growth at 37 degrees C. Carbohydrate receptors also appeared to be involved with these interactions. PMID- 8483059 TI - Lipase of Malassezia furfur: some properties and their relationship to cell growth. AB - Lipase activity of Malassezia furfur, detected with alpha-naphthyl palmitate as a substrate, appeared to be associated with the insoluble fraction of the organism. Profiles of M. furfur lipase were similar to those of Candida cylindracea lipase. The pH optimum of the lipase was acidic, pH 5.0, which is very similar to skin surface pH. The enzyme activity was strongly activated by a lipase activator, sodium taurocholate (STC). Addition of STC to the culture medium activated cell growth in a dose-dependent manner and induced hyphae production. These results suggest that M. furfur lipase plays an important role in cell growth. PMID- 8483060 TI - Cryptococcosis produced by a urease negative strain of Cryptococcus neoformans. AB - A urease negative strain of Cryptococcus neoformans was isolated form a patient with AIDS. The identification of the yeast was confirmed by physiological and pathogenicity tests. Clinically, the disseminated cryptococcal infection in our patient was identical to those reported in other patients with AIDS. PMID- 8483061 TI - Disseminated adiaspiromycosis in a patient with AIDS. AB - A case of disseminated adiaspiromycosis in an AIDS patient is described. The most notable characteristic of the infection was the extensive osteomyelitis exhibited by the patient. Positive cultures for Chrysosporium parvum var. parvum were obtained from pus taken from a lesion of the wrist during surgery as well as from sputum samples and a bone marrow aspirate. Treatment with amphotericin B controlled the fungal infection. PMID- 8483062 TI - Oxygen consumption and carbon dioxide production during liquid ventilation. AB - Liquid ventilation with perfluorocarbon (PFCV) has advantages over conventional gas ventilation (GV) in premature and lung-injured newborn animals. Indirect calorimetric measurement of both oxygen consumption (VO2) and carbon dioxide production (VCO2) during PFCV has not been previously performed. In addition, comparison to indirect calorimetric measurement of VO2 and VCO2 during GV has not been evaluated. Ten fasted normal cats weighing 2.6 to 3.9 kg were anesthetized with pentobarbital and pancuronium. Tracheostomy was performed. Gas exchange was measured across the native lung during GV and across the membrane lung of the liquid ventilator during PFCV. VO2 was measured using a modification of a previously described, indirect, closed-circuit, volumetric technique. VCO2 was analyzed by capnographic assay of the mixed-expired closed-circuit air. The VCO2/VO2 ratio (RQ) was calculated. There was no change in VO2, VCO2, or RQ during PFCV when compared with GV (VO2: GV = 5.7 +/- 0.3 mL/kg/min, PFCV = 5.6 +/ 0.5 mL/kg/min [P = NS]; VCO2: GV = 4.9 +/- 1.1 mL/kg/min, PFCV = 4.8 +/- 0.9 mL/kg/min [P = NS]; RQ: GV = 0.85 +/- 0.21, PFCV = 0.86 +/- 0.21 [P = NS]). During GV the PaO2 was higher than during PFCV (PaO2: GV = 335 +/- 70 mm Hg, PFCV = 267 +/- 83 mm Hg [P = .04]), as is expected because of the relative reduction in the inspiratory PiO2 of the perfluorocarbon during liquid ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483063 TI - Maintenance of the placental circulation to evaluate and treat an infant with massive head and neck hemangioma. AB - A maternal ultrasound was obtained because of polyhydramnios at approximately 30 weeks gestation. The study identified a fetus with a large, solid mass involving the neck and left face. Because of the concern for airway obstruction, we sought an alternative to normal delivery or routine cesarean section. At 35.5 weeks gestation the mother underwent deep halothane anesthesia followed by cesarean section. Initially, only the head and neck of the fetus were delivered and a large hemangioma was noted to involve the anterior and left neck and all of the left face to the left eye. While maintaining placental and umbilical cord circulation, the infant was successfully nasotracheally intubated. The umbilical cord was divided and the delivery completed. At 1 week of age the infant underwent partial excision of that portion of the hemangioma overlying the trachea and the left external carotid artery was ligated. The infant was successfully extubated 12 days later. In the first 4 months of life she had three episodes of platelet trapping requiring high-dose systemic steroid therapy. Beginning at 8 months of age she was begun on intralesional injections of a 50/50 solution of triamcinolone and betamethasone with a marked reduction in the size of the lesion. Preservation of the placental circulation during delivery resulted in the avoidance of a potential hypoxic or fatal event. Intermittent intralesional steroid injections appear to have played a role in the marked reduction in the size of this large subcutaneous head and neck hemangioma. PMID- 8483064 TI - Extracorporeal membrane oxygenation: support for overwhelming pulmonary failure in the pediatric population. Collective experience from the extracorporeal life support organization. AB - Data from the Extracorporeal Life Support Organization (ELSO) regarding the use of extracorporeal membrane oxygenation (ECMO) in pediatric patients with respiratory failure are reviewed. Two hundred eighty-five children between the ages of 14 days and 18 years were supported with ECMO between January 1982 and September 1991. Although these data represent the experience of 52 ECMO centers, seven centers accounted for over 50% of the total. The patients had a mean age of 33 +/- 48 months with a median age of 13 months: 137 (48%) were male and 148 (52%) were female. There were numerous primary pulmonary diagnoses: the two most common were presumed viral pneumonia (32%) and adult respiratory distress syndrome (28%). Entry criteria for ECMO, although poorly defined and specific to each institution, attempted to identify children with an 85% to 100% predicted mortality. The survival rate with ECMO was 47% (135/285). Pre-ECMO mechanical ventilatory support was extreme with an FIO2 .97 +/- .07 and a mean airway pressure (MAP) 23.6 +/- 8 cm H2O used to achieve PaO2 of 50 +/- 39 and PaCO2 51 +/- 22 mm Hg. The MAP was significantly higher in nonsurvivors versus survivors (25.3 +/- 8.7 v 22.0 +/- 7.1 cm H2O, P < .01). The duration of ECMO was 4 hours to 35.5 days with a mean of 245 +/- 165 hours, which is approximately 10 days. Duration for survivors was 222 +/- 151 hours compared with 266 +/- 176 hours for nonsurvivors. ECMO complications are divided into two categories: mechanical (directly related to the ECMO circuit) and medical (patient related).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483065 TI - Multicenter comparison of conventional venoarterial access versus venovenous double-lumen catheter access in newborn infants undergoing extracorporeal membrane oxygenation. AB - A multicenter trial was designed to compare standard venoarterial (VA) access versus single-catheter, venovenous access using the double-lumen catheter (VV DLC) for newborns with respiratory failure undergoing extracorporeal membrane oxygenation (ECMO). Twenty-seven ECMO centers participated, each submitting data from the center's most recent VA cases, and data from VV-DLC cases completed upon entering the study. Data from 135 VA ECMO cases and 108 VV-DLC cases were submitted. All diagnoses resulting in neonatal respiratory failure were submitted, including patients with congenital diaphragmatic hernia (24 patients VA bypass, 11 patients VV-DLC bypass). Overall survival in patients undergoing VA bypass was 87%, while survival in patients undergoing VV-DLC bypass was 95%. Eleven patients required conversion from VV-DLC bypass to VA bypass because of insufficient support--10 of these patients survived (91% survival). Average bypass time for newborns undergoing VA bypass was 132 +/- 7.4 hours versus 100 +/ 5.1 hours for those undergoing VV-DLC bypass. Neurologic complications were more common in the VA bypass patients, although the VV patients were more stable. Hemorrhagic, cardiopulmonary, and mechanical complications, other than kinking of the DLC, occurred with approximately equal frequency in each group. In conclusion, in newborns with adequate cardiac function, venovenous ECMO using the DLC can provide the same level of support as conventional VA ECMO, without ligation of the carotid artery. PMID- 8483066 TI - Aminocaproic acid decreases the incidence of intracranial hemorrhage and other hemorrhagic complications of ECMO. AB - Since the inception of extracorporeal membrane oxygenation (ECMO), hemorrhage has been a major complication often limiting its usefulness. This study was undertaken to evaluate the effect of aminocaproic acid (AMICAR), an inhibitor of fibrinolysis, on all hemorrhagic complications of ECMO including intracranial hemorrhage (ICH). In 1990, 49 neonates and 5 older children received ECMO therapy. None of these patients received AMICAR. In 1991, 51 neonates and 5 older children received ECMO. Forty-two of these patients who were considered to be at high risk for bleeding complications (preexisting or anticipated surgical procedures, preexisting ICH, or profound hypoxia, acidosis, coagulopathy, or prematurity) were given AMICAR. The remaining 14 low-risk neonates did not receive AMICAR, and for purposes of analysis were combined with the 1990 group. AMICAR was administered just prior to or after cannulation (100 mg/kg, intravenously) and was infused continuously at 30 mg/kg/h until decannulation. Except for the addition of AMICAR, the ECMO protocol was identical for these two patient groups. Patients who received AMICAR had significantly less bleeding while on ECMO (P = .03) and required fewer blood transfusions (P = .01) than patients not receiving AMICAR. This difference was most significant in the congenital diaphragmatic hernia and cardiac subgroups (P = .0001) and was not significant in the meconium aspiration subgroup (P = .1). The incidence of ICH in the neonatal subgroup was also significantly reduced with no patient on AMICAR developing a new or extending a preexisting ICH (P = .007). Reexploration of the cannulation site for bleeding was also reduced in the AMICAR-treated group but the difference failed to reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483067 TI - Halothane as an anesthetic for fetal surgery. AB - Halothane has become the preferred anesthetic agent during fetal surgery because it can be administered via maternal inhalation and it improves surgical exposure by relaxing the uterus. However, the effects of halothane anesthesia on fetal cardiovascular homeostasis during fetal surgery have not been documented. In 10 pregnant ewes, inhalation halothane anesthesia was administered and their fetuses were instrumented for cardiovascular evaluation. During a 1-hour period we evaluated the acute effects of halothane anesthesia on fetal hemodynamics, arterial blood gases, cardiac output, placental blood flow, total vascular resistance, systemic vascular resistance, and placental vascular resistance. Fetal cardiac output and placental blood flow were determined by the radiolabelled microsphere technique and resistances were calculated using pressure and flow data. These findings were compared to both the results we obtained in 15 fetal sheep anesthetized with the maternal administration of intravenous ketamine, and to the accepted values found in nonanesthetized, chronically instrumented fetal sheep. Our findings indicate that with halothane anesthesia during fetal surgery fetal cardiac output and placental blood flow significantly decrease, and total vascular resistance increases. Placental vascular resistance increases out of proportion to systemic vascular resistance, resulting in the shunting of blood away from the placenta. The combination of decreased cardiac output and increased shunting of blood away from the placenta causes depressed respiratory gas exchange. These findings are not present with other anesthetic agents. Halothane has significant negative effects on both the fetal heart and the peripheral vasculature which disrupt fetal cardiovascular homeostasis. Halothane is a poor anesthetic during fetal intervention. PMID- 8483068 TI - Continuous epidural analgesia in newborn infants undergoing major surgery. AB - Providing safe, effective analgesia for newborn infants undergoing major surgery remains a challenge to pediatric anesthetists and surgeons. Continuous epidural analgesia (CEA) has been shown to provide safe and effective analgesia in infants and children; however, there is little reported use in neonates. We review our experience of CEA in 14 newborn infants (32 to 40 weeks gestation) aged 4 hours to 35 days undergoing major surgery, as well as a further 6 ex-preterm (25 to 29 weeks gestation) infants aged 2 to 5 months at time of surgery. In all cases effective analgesia was achieved for up to 69 hours without complication. All infants were awake and extubated uneventfully at the completion of surgery, which lasted 5 hours in one case. None of the infants developed respiratory depression or prolonged apnea. The technique has been widely accepted by surgeons, neonatal nursing staff, and neonatologists. PMID- 8483069 TI - Epidural fentanyl infusion with patient-controlled epidural analgesia for postoperative analgesia in children. AB - The use of epidural fentanyl infusion with patient-controlled epidural analgesia (PCEA) is becoming popular for postoperative analgesia in adults. Its use has not been reported in the pediatric population. We report our initial experience with this technique in pediatric patients. The charts of all children who received epidural fentanyl infusions for postoperative analgesia between June 1991 and February 1992, were reviewed. Thirty-one patients, ages 6 to 17 years (mean +/- SD, 13.2 +/- 2.7) received epidural fentanyl infusion with PCEA for 36 operative procedures. Epidural catheters were either inserted in the lumbar (n = 14) or thoracic (n = 22) epidural space at a level based on the surgery. A fentanyl bolus of 1.38 +/- 0.43 micrograms/kg was delivered via epidural catheter just prior to the conclusion of surgery. A continuous infusion of fentanyl (0.56 +/- 0.18 micrograms/kg/h) with a PCEA bolus (0.53 +/- 0.17 micrograms/kg) available every 15 minutes was initiated in the recovery room and was utilized for 8 to 110 hours (59 +/- 27 hours). Pain and sedation were assessed by verbal descriptive scales, and side effects were noted. Alterations in dosing regimen were made for inadequate analgesia or side effects. Analgesia was assessed as excellent or good in 78% of the patients, 91% in the thoracic catheter group and 57% in the lumbar catheter group (P < .02). Patients with thoracic catheters were more likely to need their infusion and PCEA doses decreased, whereas those with lumbar catheters more often needed their doses increased (P < .05). No patient had respiratory depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483070 TI - Regional anesthesia in pediatric surgery: complications and postoperative comfort level in 174 children. AB - Postoperative pain control (PPC) in children is a difficult management problem. Systemic narcotics often result in respiratory depression, while nonnarcotic analgesics are associated with inconsistent PPC. This report reviews a 29-month (January 1989 through July 1991) experience with 174 children (aged < 18 years) who received regional PPC through indwelling catheters. There were 105 males and 69 females. Patient age ranged from 1 day to 17 years 10 months (mean age, 97 months). All catheters were placed using introduction needles ranging from 24 to 16 gauge. Agents were delivered as either continuous infusion (151 patients, 87%) or bolus injections (23 patients, 13%). Analgesics were age- and weight determined dosages of bupivacaine with or without narcotic supplementation. All patients had surgical procedures except two who had catheters placed for pain control after trauma and one who had a catheter for intractable abdominal pain of unknown etiology. Twenty-five (15%) children had thoracic incisions, 76 (43%) abdominal, 16 (9%) flank, and 54 (31%) extremity. Catheter placement included 40 thoracic epidurals (23%), 100 lumbar (57%), 27 caudal (16%), and 7 pleural (4%). Catheters were utilized for a duration of 0.5 to 8 days (mean, 2.1 +/- 1.2 days). One hundred forty-four children required no additional pain medications (83%). Thirty (17%) patients required supplemental medications. Acetaminophen was used in 6 (3%), acetaminophen with codeine in 4(2%), morphine in 18 (10%), and Percocet in 1(1%). Minor complications occurred 21 times in 16 children (9%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483071 TI - A comparison of wound instillation and caudal block for analgesia following pediatric inguinal herniorrhaphy. AB - Regional analgesia, in a variety of forms, has been shown to afford effective postoperative pain relief after pediatric inguinal hernia repair. This study compares the efficacy of wound instillation with 0.25% bupivacaine (n = 20), caudal block with 0.25% bupivacaine (n = 35), and a control group (n = 15). Outcome parameters examined include total operating room time, time to extubation, postoperative objective pain scales, and requirement for supplemental analgesics. Patients who received caudal blocks had significantly decreased emergence times (P < .002), exhibited fewer pain-related behaviors postoperatively (P < .0025), and required less narcotic to maintain normal hemodynamics (P < .05). Operating room time was not statistically different between the three groups. The use of perioperative analgesic blocks resulted in quicker awakening, a more comfortable postoperative course, and potentially earlier discharge from same-day surgery. PMID- 8483072 TI - Incarceration of inguinal hernia in infants prior to elective repair. AB - The low morbidity and good results of elective herniorrhaphy in children are adversely affected by incarceration. Since incarceration is a potentially avoidable complication, we reviewed 908 consecutive cases to determine its incidence and consequences in children awaiting elective operation for an inguinal hernia. Eighty-five of the 908 children presented with an incarcerated hernia. Thirty of these 85 patients (35%) were known to have an inguinal hernia prior to incarceration, and 25 of the 30 were awaiting elective hernia repair. The median time from surgical office visit to planned operation was 22 days, but the mean interval from office visit to incarceration was 8 days. Eighty-five percent of the children with incarcerated hernias were infants under 1 year of age. Seventy-one of the 85 patients with an incarcerated hernia (84%) had successful manual reduction. They were all admitted and had a mean hospital stay of 2.5 days. Emergency operation after unsuccessful attempts at reduction was required in the other 14 children, increasing the average length of stay to a mean of 4.0 days. Significant complications, including infarction of the testis or ovary, bowel obstruction, intestinal necrosis, wound infection, and recurrent hernia, occurred in 26 of the 85 children (31%). We conclude that incarceration is a preventable problem. Even patients scheduled for hernia repair are at risk and the operation should be performed soon after the diagnosis is made. Infants are the highest priority group, since 35% of children less than 12 months of age experienced incarceration while awaiting elective surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483073 TI - Musculoskeletal involvement in children with gastroschisis and omphalocele. AB - A review of 58 children with gastroschisis and 8 children with omphalocele showed 14 musculoskeletal problems in 11 children. These problems consisted of limb deformities in 6 children, spinal deformities in 4 children, and osteopenia in 3 children, with 1 of the osteopenic children developing pathological fractures. About one third (5/14) of the problems were arthrogrypotic in nature. The remainder were mild digital deformities, developmental or spondylodysplastic scolioses, and, rarely, congenital spinal deformities. PMID- 8483074 TI - Experimental use of high-frequency ultrasound to image bowel wall after porcine intestinal transplantation. AB - A means to monitor intestinal allografts will be crucial for the future success of small bowel transplantation. We have previously demonstrated the ability of high-frequency ultrasound (US) to diagnose porcine intestinal ischemia in vitro. The aim of this study was to compare the histologic appearance of normal porcine small bowel versus bowel undergoing acute rejection, using 8.5-MHz US images. We allowed porcine heterotopic small bowel allograft transplants to reject and then removed, at scheduled intervals from postoperative day 0 to 12, specimens of both the transplanted bowel and the native bowel. We examined the tissues in vitro with an 8.5-MHz linear array US system then studied them histologically. Histologically, the earliest changes of rejection occurred at days 4 to 5, with mild submucosal edema, endotheliitis, and vasculitis affecting the small vessels; the mucosa remained normal. By days 7 to 8, the submucosal endotheliitis became more prominent, with focal thrombosed small vessels; the mucosa now appeared abnormal with flattened villi, erosions, and necrosis. By days 10 to 12, marked submucosal edema, vasculitis, endotheliitis, and necrotic mucosa were present. Ultrasonically, normal intestinal wall has five wall layers, corresponding to mucosa, submucosa, muscularis propria, and subserosal fat. The US criteria for abnormality were loss of folds, decreased numbers of echo layers, discontinuity of layers, and a homogeneous appearance. Using these US criteria, blinded observers differentiated normal from abnormal bowel wall after transplantation with a sensitivity of 84% and a specificity of 81%. Most of the errors occurred with the day 4 and 5 specimens, which appeared nearly normal on US.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483075 TI - Conversion of xanthine dehydrogenase to xanthine oxidase during ischemia of the rat small intestine and the effect of trifluoperazine on the conversion. AB - The conversion from xanthine dehydrogenase (XD) to xanthine oxidase (XO) and the effect of trifluoperazine (TFP), a calmodulin inhibitor, on the conversion were examined during the normothermic ischemia of the rat small intestine. Rat jejunums were stored in lactated Ringer's solution (LR) at 37 degrees C for various hours after intravascular flushing with LR. The extents of the conversion from XD to XO (%XO) constituted 21.1% +/- 3.0%, 36.2% +/- 7.0%, 63.2% +/- 8.1%, and 88.2% +/- 8.6% after 0, 2, 4, and 6 hours of the preservation, respectively (control group). The preservation without the intravascular flushing showed significant increase in the %XO (99.5% +/- 6.0%) only after 6 hours compared with those in the control group (P < .05). When the intestines were stored in LR containing 50 mg/L of TFP at 37 degrees C, or stored in LR at 37 degrees C after the intraperitoneal pretreatment with 10 mg/kg of TFP 1 hour before laparotomy showed significant decrease in the extents of the conversion after 4 hours (P < .005) and 6 hours (P < .025) of the preservation, compared with those in the control group. When the dose of TFP for the pretreatment was increased to 50 mg/kg, the suppressive effect on the conversion was found even after 2 hours (P < .025) as well as after 4 hours (P < .005) and 6 hours (P < .025) of the preservation. These results suggest that TFP could be effective on reducing the XO-mediated postischemic reperfusion injury by means of inhibiting the conversion during ischemia of the rat small intestine. PMID- 8483076 TI - Mucosal permeability to 51Cr EDTA following subclinical intestinal ischemia reperfusion injury in the weanling rat. AB - The etiology of necrotizing enterocolitis (NEC) is uncertain. We have hypothesized that subclinical intestinal ischemia might result in increased mucosal permeability to intraluminal toxins or bacteria, resulting in inflammation and NEC. In order to pursue this hypothesis, we designed a series of studies to investigate whether the first assumption is correct, ie whether a subclinical ischemia-reperfusion injury (IRI) results in increased mucosal permeability. Using a model of superior mesenteric artery occlusion (SMAO) in weanling rats, we initially defined 10-minute SMAO as "subclinical" IRI (ie, 100% survival, no histological changes, and no hemodynamic instability). Mucosal permeability to a standard probe molecule (51Cr EDTA) was then measured after sham operation, or 2-minute or 10-minute SMAO. There was an early increase in permeability 30 minutes after reperfusion in the 10-minute SMAO group, which was completely reversed by 2 hours. Further studies suggested that having passed through the mucosa, the probe entered the systemic circulation via both portal venous and intestinal lymphatic routes. Subclinical intestinal IRI results in an early, reversible increase in mucosal permeability to 51Cr EDTA, which may be important in the pathogenesis of NEC. Further studies are required to fully characterize this phenomenon, and to determine the mechanisms by which it occurs. PMID- 8483077 TI - Mesenteric ischemia in hypoplastic left heart syndrome. AB - Hypoplastic left heart syndrome (HLHS) has been widely viewed as a uniformly fatal form of congenital heart disease. Between January 1984 and December 1990, 387 patients with the diagnosis of HLHS were treated at this institution. Mesenteric ischemia was clinically diagnosed in 31 patients (8% incidence) and confirmed by pathology or surgery in 25 of those patients. The mean age at the time of onset was 17.5 +/- 5.4 weeks and only 13% were premature newborns. In 80% of the patients a low perfusion state and significant hypotension were documented within 48 hours prior to the diagnosis of bowel ischemia. Nine patients (29%) required operative intervention (bowel resection 4, diffuse ischemia 3, and simple drainage 2). Overall, at operation or at autopsy, nine patients (29%) had diffuse gastrointestinal ischemia. Of 31 patients with mesenteric ischemia, 26 children (84%) died shortly after onset of the gastrointestinal symptoms regardless of means of management. Five patients (10%) initially improved with aggressive medical and/or surgical management; however, 4 subsequently died secondary to complications of their primary cardiac disease. Therefore, the overall mortality of patients with mesenteric ischemia was 97%. Previous reports have estimated that up to 7% of full-term newborns with symptomatic congenital heart disease may develop necrotizing enterocolitis (NEC). Our unique group of patients with HLHS is comprised mostly of full-term infants who developed onset of mesenteric ischemia at a mean age of 4 months associated with an underlying low perfusion state. This mesenteric ischemia has been erroneously identified as NEC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483078 TI - Effects of newly introduced chemotherapeutic agents on a cytogenetically highly malignant neuroblastoma, xenotransplanted in nude mice. AB - A human neuroblastoma xenograft, designated TNB9, was used in this experiment. This xenograft is known to have a homogeneously staining region (HSR) on chromosome 20 and to exhibit 60- to 100-fold amplification of clones 8, G21 and N myc, and showed a rapid tumor weight doubling time of 5.9 days; it represents one of the most malignant strains of human neuroblastoma. The effects of nine different chemotherapeutic agents on this xenograft were studied according to the standard Battelle Columbus Laboratories protocol, and the in vivo chemotherapeutic sensitivity assessment disclosed that Mitomycin C, Ifosfamide, and Carboplatin were highly effective against it, while VP-16, NK-171, 5 Fluorouracil, and THP-Adriamycin were ineffective. Cytogenetic and molecular cytogenetic analyses suggest that the present data may accurately predict the clinical results with these chemotherapeutic agents in treating patients in advanced stages, as did those from our previous studies. Inclusion of Mitomycin C, Ifosfamide, and/or Carboplatin into a new chemotherapeutic protocol may be recommended. PMID- 8483079 TI - Imaging of neuroblastoma in patients identified by mass screening using urinary catecholamine metabolites. AB - Between April 1983 and August 1991, mass screening in Chiba Prefecture found 25 infants to be positive for neuroblastoma based on elevated urinary levels of catecholamine metabolites. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy (BS), and 67Ga scintigraphy (GS) detected neuroblastomas in 12 of the 25 infants. The primary site of tumor was the mediastinum in 1 patient, the adrenal gland in 7, retroperitoneum in 3, and pelvis in 1. To determine the accuracy of each imaging technique, the percent sensitivity (SE), percent specificity (SP), and percent accuracy (AC) were determined for each technique from surgical findings and a follow-up study. MRI showed the highest diagnostic accuracy (100% for SE, SP, and AC), followed by CT (100%, 92%, 96%), US (82%, 92%, 88%), BS (58%, 100%, 80%), and GS (42%, 85%, 64%) in that order. MRI is most suitable for the imaging of individuals judged to be positive in the mass screening for neuroblastoma because of the advantages of visualization of the spread of tumor and the relationship of tumor to the great blood vessels, important determinants of resectability and therapy. PMID- 8483080 TI - How great is the incidence of truly congenital common bile duct dilatation? AB - In an attempt to investigate the causes of common bile duct dilatation (CBDD), activity of the pancreatic enzymes in bile aspirated from the dilated duct during laparotomy was measured in 24 children with CBDD. The reasoning behind this is the fact that the existence of activated pancreatic enzymes, namely raised activity of all enzymes accompanied by trypsin activation, can be regarded as an acquired result of an anomalous choledochopancreaticoductal junction (ACP-DJ). All of the pancreatic enzymes measured were activated in 14 cases (58.3%) but no evidence of activation of enzymes, such as trypsin or others except for amylase and lipase, was observed in the remaining 10 cases (41.7%), whether an ACPDJ was present or absent. Eight of the 10 patients with no enzyme activation (33.3% of the total) were less than 2 months old. The findings in these eight infants, which included cystic dilation or hypoplasia of the intrahepatic duct, provide strong suggestive evidence of the congenital nature of these cases. These results suggest that at least one third of CBDD cases are congenital and the remaining cases are either acquired or a combination of congenital and acquired, or both. PMID- 8483081 TI - Persistent catheter-related bacteremia: clearance with antibiotics and urokinase. AB - A patient with terminal osteogenic sarcoma and catheter-related coagulase negative staphylococcal bacteremia was treated with vancomycin and blood cultures were positive for 4 days documented with quantitative colony counts. Urokinase therapy was initiated and was associated with a transient bacteremia with markedly increased colony counts of coagulase-negative Staphylococcus prior to eradication of the catheter-related infection. We feel that the combination of urokinase and appropriate antibiotics may be an effective method to eradicate line-associated coagulase-negative staphylococcal infection in selected patients. PMID- 8483082 TI - Spontaneous umbilical fistula: a rare complication of ventriculoperitoneal shunt. AB - Although complications following ventriculoperitoneal shunt for hydrocephalus are not uncommon, leak of cerebrospinal fluid from the normal umbilicus following ventriculoperitoneal shunt is very rare. One such case is reported. PMID- 8483083 TI - Colonic atresia and Hirschsprung's disease association shows further evidence for migration of enteric neurons. AB - The seventh case of colonic atresia and Hirschsprung's disease association is presented. It is proposed that if vascular accident occurs before the eighth week of intrauterine life, it does not only result in atresia but also associates with Hirschsprung's disease. PMID- 8483084 TI - Hirschsprung's disease complicating colon atresia. AB - An infant with the rare association of colon atresia, total colonic Hirschsprung's disease, and tetralogy of Fallot is presented. While Hirschsprung's disease associated with atresia of the colon has been reported five times previously, this is the first case with associated congenital cardiac disease. As in previous reports, initial operations to relieve obstruction due to the colon atresia failed because of the unrecognized aganglionosis. This infant initially had an ileostomy performed as a newborn and then two failed attempts at closure of the ileostomy. In this case, as in four previously reported cases, histological examinations of resected colon from the initial operations were first reported as normal and only under the pressure of increasing clinical evidence was the pathology reviewed and the absence of ganglion cells appreciated. We stress the importance of suspecting the coexistence of Hirschsprung's disease and colon atresia when a functional obstruction is present after repair of the atresia. PMID- 8483085 TI - Does the type of anomalous arrangement of pancreaticobiliary ducts influence the surgery and prognosis of choledochal cyst? PMID- 8483086 TI - A review of longitudinal studies that compared periodontal therapies. AB - There have been numerous longitudinal periodontal studies that have compared the effects of two or more therapies on various clinical parameters. These studies are reviewed and their results are compiled. Both surgical and non-surgical therapy produced improvement in periodontal health. Surgical therapy tended to create greater short-term probing depth reduction than non-surgical therapy; however, the advantage was lost in some studies over time. In shallow probing depths, surgery produced a greater loss of probing attachment than non-surgical therapy. In deeper probing sites, the short-term results comparing mean probing attachment change following non-surgical and surgical therapy were mixed. In most studies, no long-term differences in mean probing attachment level change were present between non-surgical and surgical therapy. There were no differences between surgical and non-surgical therapy in any of the gingival inflammatory indices. PMID- 8483087 TI - Periodontal regeneration of human infrabony defects. I. Clinical measures. AB - A series of investigations was undertaken to evaluate the extent and predictability of periodontal regeneration with barrier membranes in deep infrabony defects. This study reports the clinical outcomes in terms of probing attachment level (PAL) gains, probing pocket depth (PPD) reduction, and recession (REC) of marginal gingiva. Forty deep 1, 2, and 3-wall combination infrabony defects treated with membranes were evaluated 1 year postoperatively following a strict plaque control regimen (mean plaque score = 6.1%, bleeding score = 4% at 1 year). A PAL gain of 6.1 +/- 2.5 mm along with a PPD reduction of 5.9 +/- 2.5 mm were observed. A PAL gain of 2 mm or more was detected in almost 90% of the treated sites. No site lost attachment. Residual PPD was 3 mm or shallower in 95% of the sites. It is concluded that treatment of deep infrabony defects according to the principles of guided tissue regeneration and a strict plaque control regimen represents an efficacious and predictable treatment alternative. PMID- 8483088 TI - Periodontal regeneration of human infrabony defects. II. Re-entry procedures and bone measures. AB - This paper evaluates the osseous healing response of 40 infrabony defects treated with guided tissue regeneration. The selected sites presented with deep periodontal lesions with a 1-, 2-, and 3-wall combination infrabony component of 6.1 +/- 2.5 mm. Baseline intrasurgical clinical measurements were compared with intrasurgical clinical measurements obtained at the 1 year surgical re-entry. A significant regeneration of bone of 4.3 +/- 2.5 mm was observed, along with a 0.4 +/- 1.9 mm resorption of the alveolar bone crest, which resulted in a 4.7 mm reduction of the original infrabony defect. Almost 90% of the sites showed a bone gain of 2 mm or more, while no site lost supporting bone; 73 +/- 31.2% of the original defect was filled with bone. The 3- and 2-wall components were filled 95 +/- 6.2% and 82 +/- 18.7% of their original depth, respectively; however, the 1 wall component was filled only 39 +/- 62.4%. It is concluded that treatment of infrabony defects according to the principles of guided tissue regeneration and a strict plaque control regimen resulted in clinically significant and highly predictable bone regeneration. PMID- 8483089 TI - Periodontal regeneration of human infrabony defects. III. Diagnostic strategies to detect bone gain. AB - Assessment of actual treatment outcome by simple and available diagnostic tests represents an important aspect in the evaluation of periodontal regenerative procedures. This report focuses on the diagnostic accuracy of different strategies to detect the original extent of bone loss and bone gain in deep vertical defects following guided tissue regeneration. Characteristics of probing attachment level and radiographic bone linear measurements were compared to a gold standard obtained as intrasurgical clinical measurements at baseline and at the 1 year re-entry operation. Radiographic linear measurements underestimated bone loss (CEJ-BD) in 55% of cases while the estimate was within 1 mm in 25% of cases. The goodness of agreement could be significantly described by a general linear model incorporating measures of defect morphology. The original level of bone loss could be best detected by an approach which consisted of adding 1.5 mm to the measured attachment level loss. Such an approach correctly estimated bone loss within 1 mm in 85% of sites. In terms of ability to detect bone gain, radiographic measurements underestimated bone gain in 55% and overestimated it in 15% of sites. Diagnostic accuracy was assessed at different threshold values of true gain. The sensitivity and specificity plots intersected at a threshold value of 2.7 mm bone gain. Conversely, measures of probing attachment level gain agreed with the gold standard within 1 mm 45% of times. Intersection of the specificity and sensitivity plots occurred at 3 mm. Classification tables are presented for both diagnostic tests at different threshold values.2+e PMID- 8483090 TI - Time-related changes of in vivo projection errors in standardized radiographs. AB - Subtraction radiography requires radiographs made with identical projection geometry. Recently a new radiographic aiming device and an x-ray beam manipulator made it possible to repeat radiographic exposures in vivo with small angular errors and to measure the angular errors occurring. The purpose of the present investigation was to study in vivo the measuring error and the angular errors produced by this new method at different time points (0, 6, and 12 months) and to assess the effect of different time intervals between exposures (0, 6, and 12 months). Ten sites were investigated. At each time point 2 exposures were made, resulting in 6 radiographs per site. For each pair of radiographs the measuring errors occurring during analysis and the projection errors were determined for each time point and for each time interval. Friedman's test and t-test were used to evaluate the errors. A difference in the measuring error of the system and in the angular errors at the time points 0, 6, and 12 months could not be detected. A time interval between exposures also did not have an effect on the measuring error. Time did not affect the vertical and horizontal angular errors measured between the radiographs producing the smallest oblique error. A combination of radiographs producing the largest oblique angular error showed an increase of the horizontal and vertical angular errors when the time interval increases. These effects, however, were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483091 TI - Development of the murine periodontium. II. Role of the epithelial root sheath in formation of the periodontal attachment. AB - Experimental manipulation of the developing murine tooth germ has provided evidence that basement membrane components on the forming root surface are involved in early periodontal attachment formation. The purpose of this investigation was to determine the role of epithelial root sheath (ERS) cells in murine cementogenesis and periodontal ligament formation using tissue separation and recombination techniques. Root dentin specimens, with and without root associated basement membrane components (D + RBM or D - RBM), were recombined with dental sac in the presence or absence of ERS. Recombinations were cultured for 2 weeks, harvested, and examined by light, electron, and immunofluorescence microscopy. Mineralized tissue formed in all tissue recombinations. However, when ERS was included in recombinations between D + RBM and dental sac, 25% of recombinations formed a periodontal ligament with fibrous attachment of the root specimen to adjacent bone. These results support the hypothesis that root and periodontal ligament formation is influenced by epithelio-mesenchymal interactions and further support a key role for ERS in these processes. PMID- 8483092 TI - The effect of treatment on the activity of salivary proteases and glycosidases in adults with advanced periodontitis. AB - Enzyme activity in whole saliva of trypsin-like protease, elastase-like protease, general protease, and three glycosidases was measured by colorimetric assays, using synthetic substrates. A study group of 24 adults with advanced periodontitis was compared to a control group of 25 subjects with healthy periodontium. Clinical parameters and levels of enzyme activity were assessed at baseline, after non-surgical periodontal therapy (at 8 months), following the maintenance phase or periodontal surgery (at 15 months), and after the maintenance phase with or without systemic chemotherapy (at 20 months). The mean values of the proteolytic enzymatic activity and the activity of two glycosidases in whole saliva were significantly higher in the study group than in the control group at baseline. After the initial treatment phase at 8 months, all three proteases were reduced significantly, but the glycosidases were still high. After all treatment phases at 20 months, the activity of both the proteases and glycosidases approximated the values of the healthy group. In the saliva samples collected prior to treatment and following non-surgical periodontal therapy, the activity of salivary elastase correlated significantly with the number of deep gingival pockets (PD > or = 6 mm) and with either gingival index (GI) or the percentage of bleeding sites (BOP%). The enzyme activity in whole saliva appears to reflect the status of periodontal health. Salivary elastase shows good potential to serve as a novel adjunct to detect destructive periodontal inflammation and to follow periodontal healing after treatment. PMID- 8483093 TI - The relationship between restoration and furcation involvement on molar teeth. AB - The purpose of this cross-sectional study was to examine the correlation between the presence of a crown (CR) or a proximal restoration (RE) and furcation involvement (FI) on molar teeth. Data were collected from 134 periodontal maintenance patients who had restored and non-restored molars present both with and without FI. A majority of the restorations that were present in these patients had been in place for at least 5 years prior to the study. First and second molars were examined clinically using the following criteria: CR, RE, FI, mobility (MO), and probing periodontal attachment level (AL). Data were analyzed with a statistical program utilizing Pearson chi-square and the pair-difference t test. The results indicated that molars with CR or RE had a significantly (P < 0.01) higher percentage of FI but no greater mobility when compared to molars without restorations. Mean probing periodontal attachment loss was greater for restored than non-restored molars but only with marginal significance (P = 0.051). There was a greater difference in mean AL between restored versus non restored maxillary molars than for mandibular molars. This cross-sectional study provides evidence that molars with crowns or restorations involving the proximal tooth surfaces had a higher prevalence of FI and greater AL than molars without restorations. PMID- 8483094 TI - Localized osteomyelitis secondary to endodontic-implant pathosis. A case report. AB - This case report documents the placement of a single implant fixture in an incisor extraction socket, with the adjacent lateral incisor developing periapical pathosis within 2 weeks. This root-end inflammatory process proceeded to communicate with the surface of the implant fixture. Although endodontic therapy was performed within one week on the devitalized tooth, and extensive osteomyelitis developed around the implant. Three weeks after placement, the fixture had to be removed. The osteotomy site appeared to be healing uneventfully during the one month follow-up period. Seven possible causes for this occurrence are discussed. PMID- 8483095 TI - The results of efforts to improve compliance with supportive periodontal treatment in a private practice. AB - Patients who receive routine supportive periodontal treatment (SPT) tend to keep their teeth longer and enjoy greater periodontal health than those individual who do not receive this therapy. Previous studies have found less than optimal compliance to suggested SPT. The study reported in this paper covered 5 years of patient data and measured the effects of efforts to improve compliance in a private periodontal practice. These efforts included attempts at simplifying compliance, maintaining records of compliance, informing patients of the consequences of noncompliance, and attempting to identify noncompliers before active periodontal therapy was initiated. The results were measured against a similar group studied in previous work within the same office published in 1984. The main finding of the present study was an increase in complete compliance from 16% in 1984 to 32% in 1991. This increase came largely at the expense of the noncompliant group. The reason for the increase in compliance is likely due to efforts to increase compliance carried out in the office. However, other factors such as change in the hygiene practice law, increased public awareness of dental needs, and economic depression may also have affected compliance. This information suggests that noncompliance can be reduced if the problem is recognized and efforts are made to increase compliance. PMID- 8483096 TI - Thick free gingival and connective tissue autografts for root coverage. AB - Studies have shown partial to complete root coverage of denuded root surfaces with the use of thick free gingival autografts (FGGs) or subepithelial connective tissue autografts (CTGs). The purpose of this study was to determine which technique would result in more predictable root coverage of Miller Class I and II marginal tissue recession defects. Paired defects in 10 patients were randomly selected for treatment with either the FGG or the CTG. With stents as reference points, soft tissue recession was measured with a calibrated probe presurgically and 3 and 6 months postsurgically. No significant differences between paired sites in presurgical defect dimensions were found. One patient was dropped from the study for noncompliance with postoperative instructions. The mean percentage of root coverage for the CTG 3 and 6 months postsurgery for the remaining 9 patients was 78% and 80%, respectively. The mean percentage of root coverage for the FGG was 43% at both periods. The difference in root coverage between the 2 techniques was significant (P < 0.03). Complete root coverage was gained in 5 of 9 CTGs but only in one of 9 FGGs. Both techniques resulted in a significant improvement in keratinized tissue and probing attachment level, with most of the changes having occurred during the first three months postoperatively. Results suggest that the CTG may provide a greater percentage of root coverage than the FGG and that both techniques will effectively increase the width of keratinized tissue. PMID- 8483097 TI - [Efforts toward the formulation of the therapeutic stereoisomer of ibuprofen]. AB - In an on going effort to optimize ibuprofen antiinflammatory therapy, development studies on the active stereoisomer of ibuprofen have been conducted. The effects of pharmaceutical processing on the racemate (RAC-ibuprofen) and the enantiomer (S(+)-ibuprofen) were investigated. The formulation of the new stereospecific system, was impossible using wet granulation. The pharmaceutical development of S(+)-ibuprofen using direct compression appeared as a practical solution to this problem. The biopharmaceutical properties of the resulting tablets were well within pharmacopeia requirements. Nevertheless, mixing S(+)-ibuprofen with the excipients induced a drop in the enthalpy of fusion and after compaction, a low temperature eutectic appeared on the differential scanning calorimetry endotherms. Aging studies indicated that the raw material and pharmaceutical mixtures of S(+)-ibuprofen should be stored under strictly controlled conditions or processed immediately. PMID- 8483098 TI - A contribution to the structure-activity relationship in glutamate receptor ligands: 1. omega-Aminophosphonic acids do not antagonize NMDA receptors. AB - Pharmacological properties of a series of alpha, omega-diamino-omega phosphonocarboxylic acids and alpha, omega-diamino-alpha, omega-bis(phosphonic acids) on different excitatory amino acids mediated responses have been tested in CA1 rat hippocampal neurones, using intracellular recordings and current and voltage clamp techniques. In contrast with known antagonists as D(-)2-amino-5 phosphonopentanoic acid (AP-5) and 2-amino-4-oxo-5-phosphonopentanoic acid, which completely abolished the NMDA-response, no antagonistic activity was found. We conclude that the introduction of an omega-amino function abolishes the NMDA antagonistic activity of alpha-amino-omega-phosphonocarboxylic acids. PMID- 8483099 TI - A contribution to the structure-activity relationship in glutamate receptor ligands: 2. Characterization of 2-amino-4-oxo-5-pentanoic acid as NMDA receptor antagonist. AB - Pharmacological properties of 2-amino-4-oxo-5-phosphonopentanoic acid (AOPA) on excitatory amino acids mediated responses have been tested in CA1 rat hippocampal neurones, using intracellular recordings and current and voltage clamp techniques. These properties were compared with those of the well-known NMDA antagonist, D(-)2-amino-5-phosphonopentanoic acid (AP-5). AOPA completely abolished the response to NMDA but had no effects on the responses to AMPA, quisqualate and kainate. In voltage clamp experiments AOPA antagonized NMDA induced currents and produced a parallel shift of the NMDA concentration-response curve. Schild analysis gave a Kd value of 26 microM. AP-5 also produced a similar shift in this curve with a Kd of 6.9 mu. PMID- 8483100 TI - The effects of the tabletting machine speed on physical characteristics of pharmaceutical powders. AB - During compaction, crystallised materials are subjected to fragmentation which depends not only on the deformation undergone but also on the punch speed of the tabletting machine. Then, this process is followed by reagglomeration of the ground particles which also depends on the punch speed. Likewise, it was shown that materials with a relatively low specific heat such as Emcompress and acetylsalicylic acid are more sensitive to machine speed than boric acid or sodium chloride. From the present study it appears that tablet hardness is not a sufficient criterion to guarantee the reproducibility of a production batch. PMID- 8483102 TI - [Reactions and interactions of drugs]. PMID- 8483101 TI - [Some factors influencing the bioavailability of zinc in oral pharmaceutical dosage forms]. AB - Absorption and distribution of zinc in 6 dosage forms were determined in 10 subjects by performing a pharmacokinetic study of the serum zinc profile after oral administration of a dose corresponding to 45 mg elemental zinc. The aim of this study was to document the influence on zinc bioavailability of factors such as the chemical form of zinc, the pharmaceutical form, and the division of the administered dose. The pharmacokinetic parameters indicate for gelatin capsules without excipients taken in a non divided dose better performances for zinc gluconate in comparison to zinc sulfate. Concerning the pharmaceutical form, little difference is observed between an aqueous solution and a gelatin capsule for zinc sulfate and a non divided dose; on the contrary, a commercial gelatin capsule containing zinc gluconate with various excipients show better performances than gastro-resistant tablets when zinc intake is 3 times 15 mg. Finally, the division in 3 parts of the dose of zinc sulfate given in gelatin capsules very significantly improves zinc absorption. These results demonstrate the interest of the developed pharmacokinetic method in the assessment of zinc bioavailability in different pharmaceutical dosage forms. PMID- 8483103 TI - The immunoneuroendocrine role of melatonin. AB - A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MIIO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as gamma-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ. PMID- 8483104 TI - Antiproliferative effect of pineal indoles on cultured tumor cell lines. AB - The in vitro antiproliferative action of pineal indoles on several tumor cell lines including melanoma (B16), sarcoma (S180), macrophage-like cell line (PU5), fibroblasts (3T3), and choriocarcinoma (JAr) was examined by measuring the incorporation of 3H-thymidine by the tumor cells, and, in the case of melanoma cells, by also measuring the incorporation of 3H-leucine and 3H-uridine. Uptake of crystal violet was used to assess the viability of the tumor cells. The order of inhibitory potency of the indoles was found to be methoxytryptamine > melatonin, methoxytryptophol, hydroxytryptophol, and methoxyindoleacetic acid > serotonin and hydroxyindoleacetic acid. The possibility of an adverse effect of the indoles on the viability of normal cells was also investigated by employing a primary culture of rat hepatocytes. The release of glutamate-oxaloacetate transaminase by hepatocytes was not affected by the indoles, although the release of glutamate-pyruvate transaminase was increased to a small extent and the uptake of crystal violet was slightly inhibited. PMID- 8483105 TI - The role of the pineal in the control of the daily patterns of neurohypophysial hormone secretion. AB - Plasma concentrations of neurohypophysial hormones show clear rhythms over 24 hr which can be suppressed by exposure to constant light, an observation consistent with pineal involvement. A study has therefore been performed on the changes in the hormone levels in the hypothalamus, posterior pituitary, and plasma over 24 hr in control, pinealectomised, and sham pinealectomised animals to determine if the pineal could play a role. Water intake, urine excretion, packed cell volume, plasma osmolality, and electrolytes were also monitored. Pinealectomy had little effect on fluid balance, but after 8 weeks for oxytocin and 2 weeks for vasopressin the morning values (0700-0800) for the circulating concentrations of the hormones were significantly higher in the pinealectomized group compared with the combined sham operated and unoperated groups (pineal intact). By contrast, the pituitary vasopressin was significantly lower in the pinealectomised group. The increase in plasma oxytocin and vasopressin seen over the hours of daylight and accompanying fall in plasma osmolality seen in the pineal intact group were absent in the pinealectomised group. Similarly, the evening fall in pituitary hormone concentrations and increase in hypothalamic hormone content were absent in the pinealectomised animals. After 10 days of exposure to constant light, the fall in plasma osmolality in the pineal-intact animals over the day was no longer significant; instead a significant increase in plasma osmolality and sodium was seen in the pinealectomised group. Exposure to constant light, while altering the patterns of neurohypophysial activity in the pineal intact group, had little effect on the pinealectomised animals. PMID- 8483106 TI - A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p formylphenyl)sulphonylurea. AB - We investigated the metabolism of tolbutamide by using synthetic 1-butyl-3-(p formylphenyl)sulphonylurea (ATB), an intermediate in the metabolic pathway of tolbutamide. ATB (40 mg kg-1) administered intravenously to rabbits was oxidized to 1-butyl-3-(p-carboxyphenyl)sulphonylurea (CTB) and also reduced to 1-butyl-3 (p-hydroxymethylphenyl)sulphonylurea (HMTB). Therefore, it is likely that in the metabolism of tolbutamide, the oxidation of HMTB to ATB involved the reverse reaction, suggesting the reduction of ATB to HMTB. The oxidation of ATB to CTB was inhibited by disulfiram pretreatment. ATB was detected in the blood following intravenous administration of HMTB in rabbits pretreated with disulfiram. These results, confirm that ATB is an intermediate in the oxidative metabolism of tolbutamide in the rabbit. PMID- 8483107 TI - Pharmacokinetics and extracellular distribution to blood, brain, and muscle of alovudine (3'-fluorothymidine) and zidovudine in the rat studied by microdialysis. AB - Microdialysis was applied to sample the free drug concentration in the extracellular fluid in brain, muscle, and blood of rats given alovudine (n = 6) (3'-fluorothymidine) or zidovudine (n = 5) (25 mg/kg s.c.). Alovudine and zidovudine were analyzed by means of high performance liquid chromatography (HPLC) with UV detection. The assay for zidovudine was validated by a radioimmunoassay. In addition, the plasma protein binding of the drugs was measured by microdialysis in vitro. The concentrations attained in blood and muscle were similar for each drug, with a Cmax of 57 microM (blood) and 54 microM (muscle) for alovudine and 38 and 46 microM, respectively, for zidovudine. In contrast the Cmax in brain was 8 microM for alovudine and 4 microM for zidovudine. The peak concentration was attained 20-40 min after injection in blood and muscle and 40-60 min after injection in the brain. The half-lives of zidovudine in both blood and muscle were 37 min and in brain 69 min. For alovudine the corresponding half-lives were significantly longer: 61, 58, and 105 min, respectively. The ratio of the AUC0-180 brain/blood was 0.257 for alovudine and 0.186 for zidovudine. The plasma protein binding of zidovudine was 10%, while alovudine was virtually unbound. PMID- 8483108 TI - A prospective study of HIV-seropositive asymptomatic women of childbearing age in a developing country. AB - An observational study of 140 HIV-seropositive asymptomatic women of childbearing age was conducted in Haiti from 1984 to 1992 as part of a larger natural history study. Forty-four women were pregnant or became pregnant during the study period. The progression to HIV-related disease, AIDS, and mortality from AIDS was compared in the pregnant and nonpregnant cohorts. The mean follow-up time was 44 months. Overall, 32 of the 140 women (38%) developed AIDS, and 26 (19%) died from AIDS during the study period, with a cumulative AIDS incidence rate of 16% at 3 years after study entry. There was a trend toward earlier manifestation of HIV related symptoms among the pregnant cohort, but no significant difference was observed in the rate of progression to AIDS or death between the pregnant and nonpregnant women. PMID- 8483109 TI - Functional status and well-being in a placebo-controlled trial of zidovudine in early symptomatic HIV infection. AB - To determine the effect of zidovudine on functional status and well-being in patients with early symptomatic human immunodeficiency virus (HIV) infection, 70 subjects in a randomized, placebo-controlled trial (ACTG Protocol 016) were observed for 1 year using a brief quality-of-life questionnaire. Thirty-four subjects were assigned to placebo and 36 subjects to zidovudine, 200 mg orally every 4 h (1,200 mg daily). Functional status and well-being were measured every 3 months using a 30-item self-administered questionnaire derived from health ratings from the Medical Outcomes Study. The mean changes from baseline for zidovudine versus placebo groups were compared using paired and two-sample t tests. Subjects receiving a placebo reported better quality of life compared to baseline than subjects receiving zidovudine at 24 weeks for all dimensions of well-being, including overall health, energy, mental health, health distress, pain, and quality of life. The difference between the two groups' changes from baseline for overall health was 11.5 points on a 100-point scale (p = 0.02), and 11.1 points for energy (0.002). There were no differences between changes from baseline along various dimensions of functional status (physical, social, role, and cognitive function). At 52 weeks both groups reported worse overall health than at baseline, and changes in scores were more similar for the two groups. Although zidovudine has previously been demonstrated to delay progression of disease for patients with mildly symptomatic HIV infection, early in treatment the net effect of a 1,200 mg daily dose of zidovudine may diminish patients' subjective well-being.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483110 TI - Disseminated Penicillium marneffei infection associated with human immunodeficiency virus: a report of two cases and a review of 35 published cases. AB - Penicillium marneffei, a dimorphic fungus that is endemic in southeast Asia, causes deep-seated infection in humans and rodents. About 20 cases have been reported among the local populations of China, Thailand, and Hong Kong, and 35 cases have now been described in patients infected with the human immunodeficiency virus (HIV). We present a review of the literature and report two additional cases. Both immunocompromised and apparently immunocompetent hosts tend to develop disseminated, symptomatic infection. HIV-infected patients having travelled to southeast Asia and presenting with fever, skin lesions, hepatomegaly, adenopathies, or lung disease should be investigated for Penicillium marneffei infection. The diagnosis is based on the demonstration of the organism in clinical specimens. Treatment with amphotericin B or itraconazole is generally successful, but maintenance therapy is warranted for patients with an underlying immunodeficiency. PMID- 8483111 TI - Quality of life and health service use among HIV-infected patients with chronic diarrhea. AB - Health-related quality of life and the utilization of health resources are important components of the evaluation of patient outcome in HIV infection because medical problems are often progressive and debilitating, and treatment is palliative. We evaluated quality-of-life measures and resource utilization of patients with AIDS and/or CD4 lymphocytes < 200 who had symptoms of chronic diarrhea and compared them with similar patients with AIDS and/or CD4 lymphocytes < 200 without diarrheal symptoms. Annual charges were 50% higher for patients with chronic diarrhea ($24,567 versus $14,471 for the comparison group, p < 0.01). Higher charges for the patients with diarrhea were a result of more physician visits and diagnostic testing. Quality-of-life scores were poor for all patients, but deterioration over the year in role functioning (social activity, daily living, energy, cognition) and general health was clearly evident (p < 0.01) for the patients with chronic diarrhea. These patients also suffered significant work loss and reported greater need for assistance in the home. These data suggest that HIV-infected patients with diarrhea experience marked decreases in quality of life and that care for patients with chronic diarrhea is costly. Relatively little attention has been paid to this debilitating syndrome, and current treatment options rarely provide permanent relief. Research and innovation in this area are needed; an estimated 25-50% of HIV-positive individuals suffer from this symptom complex. PMID- 8483112 TI - HIV vaccine trials: some design issues including sample size calculation. AB - Anticipating the availability of one or more candidate HIV vaccines for efficacy testing in the next few years, public health agencies are now planning for the conduct of large-scale efficacy trials. We expect these trials to be randomized, double-blind, placebo-controlled studies with prevention of infection as the primary goal. We discuss in detail factors that influence sample size. Factors most influential are the incidence rate of HIV infection in the study population and the minimum efficacy at which a vaccine is still considered acceptable. The smaller either of these factors is, the larger the sample size will be. The desire to complete trials quickly, the gradual accrual of benefit from vaccination, the inaccuracies of assays to detect infection, the need to counsel participants to avoid exposure to HIV, and loss to follow-up all tend to drive up sample size. To illustrate, 83 subjects per study arm suffice to detect 90% efficacy in a population with a 7% annual risk of infection. This assumes a 3 year study with accrual completed in 1 year, no loss to follow-up, and Types I and II error rates of 5 and 10%, respectively. In contrast, 4,254 subjects per arm are required to identify a 60% effective vaccine in a population with a 1% annual risk. The study is also shortened to 2 years, assumes a 5% annual loss to follow-up, and supposes that the full benefit of vaccination is achieved in 6 months. The most realistic assumptions indicate that trials are very likely to require several thousand participants. Limitations of the proposed designs are also discussed. PMID- 8483113 TI - Low education as a possible risk factor for cognitive abnormalities in HIV-1: findings from the multicenter AIDS Cohort Study (MACS). AB - The present study reports new and unexpected results of cognitive abnormalities among human immunodeficiency virus type 1 (HIV-1) asymptomatic subjects in the Multicenter AIDS Cohort Study. The major purpose of our analyses is to estimate the separate and combined effects of serostatus and education level on the prevalence of cognitive abnormality. Cognitive "abnormality" was defined as performance that deviated > or = 2 SDs below the mean of the total seronegative group on at least one of the five neuropsychological screening tests (Grooved Pegboard, Verbal Fluency, Digit Span, Symbol Digit Modalities, Rey Auditory Verbal Learning). The predicted prevalence of cognitive abnormality was 38% in seropositive individuals with no more than 12 years of education, compared with < 17% in the other education-serostatus groups. This interaction between education level and serostatus remained after controlling for the possible confounding effects of age, ethnicity, CD4 level, depression, prior drug history, and learning disability using logistic regression. To account for these findings, we suggest that low education might reflect an indirect index of lower reserve capacity (i.e., a risk factor) that lowers the threshold for neuropsychological abnormalities in cases of early HIV-1 infection. PMID- 8483114 TI - Private medical insurance among Philadelphia residents diagnosed with AIDS. AB - We used medical insurance information gathered on each Philadelphia resident with AIDS to examine time trends in private medical insurance at the time of diagnosis. The proportion of AIDS patients with private medical insurance decreased from 51.9% in July-December 1988 to 28.6% in July-December 1991. During the same time period, an increasing proportion of people diagnosed with AIDS were female, poor, members of minority groups, or abusers of injection drugs. A discrete multivariate model showed that the (point) prevalence of private medical insurance at AIDS diagnosis decreased significantly with time, even after adjustment for changes with time in the age, gender, race, estimated income, history of injection drug use, and history of homosexual contact of those who were affected with AIDS. Thus the decreasing prevalence of private medical insurance among people newly diagnosed with AIDS does not simply reflect changes in the demographic and behavioral characteristics of the people affected. PMID- 8483115 TI - A comparison of drug use and HIV infection risk behavior between injecting drug users currently in treatment, previously in treatment, and never in treatment. AB - We compared three groups of injecting drug users in a large cross-sectional study on HIV/AIDS and risk behaviors in Sydney, Australia, to determine what differences existed between those who had never been in treatment (n = 458), had previously been in treatment (n = 387), and were currently in treatment (n = 367). Drug use for those currently in treatment was assessed during the last typical using month before treatment. Those previously and currently in treatment were similar in terms of drug use patterns and HIV risk-related injecting behaviors. Those never in treatment were younger, had a lower level of HIV risk related injecting behaviors, and reported lower drug use and less involvement in the drug subculture. There was little difference between the three groups on HIV risk-related sexual behaviors. These data suggest that those never in treatment are less dysfunctional and possibly less involved in drug-using careers, whereas there appears to be a close relationship between being previously and currently in treatment. PMID- 8483116 TI - HIV-1 HxBc2 strain encodes a truncated vpr gene product of 78 amino acids. PMID- 8483117 TI - Cutaneous ultrasound for evaluation of Kaposi's sarcoma. PMID- 8483118 TI - Recombinant human erythropoietin in the treatment of anemia in AIDS patients receiving concomitant amphotericin B and zidovudine. PMID- 8483119 TI - Serosurveillance of HIV infection at a neuropsychiatric center in south India. PMID- 8483120 TI - Preventing HIV spread in homo/bisexual men: how effective is it? Experience from the National Mandatory HIV Registry in Denmark. PMID- 8483121 TI - Repair of fractured porcelain restorations with composite bonded porcelain laminate contours. PMID- 8483122 TI - Restoring a calcified tooth with a cast pin-retained gold dome as support for a fixed prosthesis: a clinical report. PMID- 8483123 TI - Immediate rehabilitation after total glossectomy: a clinical report. AB - Rehabilitation has psychological and physical components. Planning and discussion with the surgeon and patient before surgery can often ease the impact of treatment and help to establish reasonable postoperative goals. When prior planning is not possible, the physical and psychological impact can be severe. In addition, consideration must be given to the needs of the primary postsurgical provider, in this case the spouse of 50 years. By allowing the wife to observe the procedures and keeping her fully informed of the desired outcome and goals, her psychological concerns were also addressed. Use of light-cured resin material can aid in providing definitive and rapid maxillofacial prosthetic treatment. PMID- 8483124 TI - Five-year study of all-porcelain veneer fixed partial dentures. AB - Improvements in enamel-dentinal bonding systems combined with the introduction of new ceramics have encouraged replacement of missing anterior teeth in specific patients with porcelain veneer fixed partial dentures. Metal substructures are not needed, and more natural tooth structure can be preserved because the preparation of abutments is conservative. Twelve porcelain veneer fixed partial dentures were monitored for 5 years, and fractures attributed to degradation of the gingival margins occurred in the veneer surface of the fixed partial dentures. The success rate of 75% was dependent on rigid patient selection criteria, strength of the major connectors, and precise adjustment of occlusion to prevent overloading. The failing margins were attributed to the degeneration, attrition, and deterioration of the composite resin cements. Despite these limitations, patients were extremely satisfied with the esthetics. Improvement in the mechanical properties of composite resin cement will ameliorate the prognosis with this approach. PMID- 8483125 TI - In vitro marginal leakage in varnished and lined amalgam restorations. AB - Black's class I classic cavity preparations were completed in 440 extracted, intact human premolars and restored with two silver amalgams and five different base materials with and without cavity varnish, which resulted in 20 combinations. A standard fluorescent dye test was performed and the percentage of marginal leakage recorded after storage for 7 days, 3 months, and 1 year in 1% NaCl at 20 degrees C. The results were computed by use of a linear logistic statistical analysis with a critical level of statistical significance of p < 0.05. Sealing improved with time and there was consistently better sealing in the first months without varnish, but after 1 year this was not significant. The low copper amalgam recorded better sealing than the high-copper amalgam. A calcium hydroxide base promoted sealing but base-free cavities performed second best. Sealing declined with 1 year if Dycal base was used. Zinc-containing bases exhibited poor sealing, even those containing tin. Base solubility can improve sealing in calcium-containing bases but not in zinc-containing bases. PMID- 8483126 TI - Effect of design of prefabricated post heads on core materials. AB - This study investigated post-core adaptation as it relates to core materials and post-head configuration. A total of 360 samples that consisted of three prefabricated post systems and three core materials of amalgam and composite resin of 1 and 3 mm post-head-covering thicknesses were made. Composite resin with a post-head covering of 3 mm was most resistant to compression, whereas amalgam was most resistant to retentive forces. The addition of titanium to composite resin as a reinforcement filler did not improve resistance to either compressive or tensile forces. PMID- 8483127 TI - Scanning electron microscope analysis of tooth enamel treated with rotary instruments and abrasives. AB - This study compared the effects of various rotary instruments and polishing agents on tooth enamel. Topographical features of enamel were studied at consecutive stages of polishing with photoanalysis of scanning electron micrographs. The results indicate that enamel modified by diamond burs may be polished to produce the smoothest surface with white finishing stones, Ceramist finishing points, and flour of pumice. PMID- 8483128 TI - A new device for blockout procedures in rotational path removable partial dentures. AB - The rationale of a rotation axis is discussed and on this basis a blockout device is designed for rotational path removable partial dentures. This device has three basic components, which are (1) the acrylic resin block, (2) the rotation axis, and (3) the functional part. In the blockout procedures for removable partial dentures with tilted mandibular molars, the rotation axis of the prosthesis is first localized by the blockout device. A knife edge, made of Duralay resin that corresponds to the survey lines of teeth to be used as supports, is constructed and is joined to the functional part of the blockout device. Blockout regions are determined by the rotational movement of the Duralay resin knife edge along the rotation axis of the blockout device. In addition to the function of blockout, the device can also be used to analyze diagnostic casts for critical undercuts. Internal and external types of blockout devices are also discussed. PMID- 8483129 TI - Minimizing biomechanical overload in implant prostheses: a computerized aid to design. AB - Implant-supported prostheses must be able to withstand the load capabilities of individual patients to overload them. The gold alloy screw in the Branemark system is by intention the weakest component. Therefore, if cantilever lengths can be designed so that occlusal forces distributed to individual fixtures are limited to the gold screws' ability to accept them, breakage-free performance may be assured. Models, such as that of Skalak, are capable of developing the required analytical processes to provide the information necessary to achieve this design. Unfortunately, the overt mathematical complexity of the Skalak model has militated against its routine use in the operatory. Its computational aspects are, however, eminently suited to computerization and indeed provide the basis for the computer program that is described in this article. This program is simple to apply clinically and, when used in conjunction with available load parameters of gold screw performance, can provide the clinician with a routine and scientific basis for rational implant prosthesis design. PMID- 8483130 TI - Evaluation of three impression techniques for osseointegrated oral implants. AB - The purpose of this in vitro investigation was to determine the accuracy of gypsum casts produced from impressions made with polyether, polyether and impression plaster, or polyether and acrylic resin for the fabrication of osseointegrated implant prostheses. Strain gauges were attached to a master framework to determine the passivity of fit of the framework to sample casts made by the three impression techniques. Strain values were statistically compared by one way analysis of variance and Duncan's multiple range test. A statistically significant difference was found between the three impression techniques tested (p < 0.05). The results of this investigation revealed that none of the impression techniques resulted in an absolutely passive framework fit. However, of the techniques tested, the polyether alone resulted in the closest duplication of the master cast. PMID- 8483131 TI - New surgical obturator prosthesis for hemimaxillectomy patients. AB - Many materials have been used to make immediate and intermediate obturator prostheses for the hemimaxillectomy patient. The weight of the obturator prosthesis is a major hindrance. A new thermoplastic material, Polysar, is described to create a hollow obturator extension for immediate and intermediate lightweight obturator prostheses. PMID- 8483132 TI - Influence of salivary levels of mutans streptococci on colonization of crown margins: a longitudinal study. AB - Initial colonization of mutans streptococci in 36 crown margins of 21 patients was studied. Before cementation, salivary concentrations of mutans streptococci and Lactobacillus sp, microorganisms associated with dental caries, were determined. Within 1 week 25% of the selected crown margins in subjects with low salivary levels of mutans streptococci and 89% in subjects with high salivary levels were colonized. High salivary counts of lactobacilli seemed to reflect conditions that enhanced the risk of colonization of mutans streptococci. The results suggest that, before cementation of fixed prosthodontics, measures should be taken to control the salivary concentrations of these organisms to reduce the susceptibility to recurrent caries. PMID- 8483133 TI - Custom characterization of the provisional restoration. AB - The fabrication of esthetic custom provisional restorations that provide optimum esthetics and function accomplished with minimal chairside time is described. The effects of mamelons, translucency, and incisal haloes are reproduced to mimic natural dentition. The technique is based on a provisional shell that is made in the laboratory and relined intraorally for a more precise fit. In addition, it can be characterized chairside to better satisfy the esthetic demands of the patient. The laboratory-processed shell allows us to attain optimal physical characteristics with auto-polymerizing methylmethacrylate resin. PMID- 8483134 TI - Engraved fixed restorations to facilitate identification in forensic dentistry. AB - A procedure for making accurate identification markings on metal crowns and fixed partial dentures with minimal cost is described. The markings can aid in identification of unknown bodies within a short period of time if this procedure becomes routine and is recognized by forensic odontologists. PMID- 8483135 TI - Make luster tabs for use in matching texture of porcelain surfaces. PMID- 8483136 TI - A technique to reposition dies on the working model during fixed prosthodontic procedures. PMID- 8483137 TI - An instrument for placing depth cuts in a full-contour wax-up. PMID- 8483138 TI - Expeditious delivery of full veneer crowns. PMID- 8483139 TI - Elimination of a food impaction problem in the posterior maxillary region. PMID- 8483140 TI - Removal of self threading pins from dentin with ultrasonics. PMID- 8483141 TI - A threaded ball for the survey of mounted casts. PMID- 8483142 TI - Vinyl polysiloxane flasking of an ocular prosthesis. PMID- 8483143 TI - The degree of zinc phosphate cement coverage of complete crown preparations and its effect on crown retention. PMID- 8483144 TI - [Spin-echo anatomy of the larynx in MRI at 1.5 T]. AB - The larynges of 8 healthy and informed volunteers were studied with a superconductive MR unit at 1.5 T together with those of 10 patients with extra laryngeal pathologic conditions. The study was performed with round surface coils (5'') and with delicated sellar coils in the anterior neck. Slices were 5 mm thick, and acquired on the coronal, axial, and sagittal planes, with T1 weighting; axial scans were repeated in the same locations with double echoes, with proton-density and T2-weighting. Five patients underwent additional scans after Gd-DTPA. The larynx of a semi-frozen cadaver was examined with sellar surface coils, on similar scanning planes and with similar pulse sequences to those described above; the larynx was removed, investigated with mammographic technique, and subsequently analyzed with thin CT slices and a high-resolution reconstruction algorithm for the study of laryngeal cartilage. Axial anatomical sections were then compared with MR and CT scans, and the anatomical structures were recognized on the triplanar MR scans of a volunteer's larynx. Besides MR anatomy of supporting laryngeal structures, the authors describe in detail the muscles, plicae, spaces and cavities which can be identified on the various planes, together with the changes in signal after Gd-DTPA. PMID- 8483145 TI - [Myocardial metastasis of bronchial carcinoma. Disclosed by x-ray computed tomography]. AB - One case of cardiac metastasis of epidermoid carcinoma discovered with CT during the preoperative assessment is reported. The authors stress that the discovery of cardiac metastases in vivo is relatively infrequent. They emphasize the role of imaging, which allows ruling out the operation in these cases. PMID- 8483146 TI - [Colonic duplication disclosed in adults. A case]. AB - We report about one case of asymptomatic duplication of the colon, which was diagnosed with a barium enema in an adult. This condition is rare, especially in the tubular form such as described in this case. The discussion is associated to a review of the literature. PMID- 8483147 TI - [Biliary cystadenocarcinoma. Apropos of a case]. AB - Biliary cystadenocarcinoma is rare biliary ductal neoplasm, usually occurring in middle-aged women, which arises in a healthy liver, with a better prognostic than other malignant tumors of the liver. We report a new case documented by echography, CT scan and MR. Echography showed multiple heterogeneous and septate masses with fluid-fluid level and dilatation of the intra-hepatic biliary ducts. CT showed multilocular cystic masses with internal septa and papillary excrescences showing contrast enhancement and no calcification. MR displayed a rather intense and variable signal in some parts of the masses on T1 weighted images, flasching on T2 weighted images, corresponding to a hemorrhagic fluid, confirmed by surgery. On T1 weighted images after gadolinium administration, the masses were less well visualized. PMID- 8483148 TI - [The tibial slope. Proposal for a measurement method]. AB - The posterior inclination of the tibial plateaus relative to the longitudinal axis of the bone, also called tibial slope, is important to know for the pathology of the cruciate ligaments and to lay some knee prostheses. We have chosen a reproducible method to measure it, on the basis of a large radiograph of the lower limb. A radio-anatomical analysis of the morphology of the tibia has first been carried out to properly choose axes that are easy to find and useful in practice. The accuracy of the measurement is to within one degree. In adults, the slope ranges from 0 to 18 degrees, according to the subjects, with variations form one knee to the other. PMID- 8483149 TI - [Adamantinoma of the tibia. X-ray computed tomographic and MRI study. Apropos of a case]. AB - Adamantinoma of the long bones in a very rare tumor that mainly affects the tibia. Its diagnosis is difficult both radiologically, as the lesion appears as a poorly specific metaphyseal lacuna with or without periosteal reaction, and histologically. Its prognosis used to be guarded because of recurrence and of possible metastatic diffusion, but it has been considerably improved by wide resection with reconstruction. On the occasion of a new case, the authors describe the appearance observed with MRI and the merits of this examination for the preoperative assessment. PMID- 8483150 TI - [MRI in the pre-operative evaluation of lesions of the rotator cuff]. AB - The authors report a series of 38 patients who had been examined by MRI and then operated for a rotator cuff syndrome. The correlation between the description of the cuff lesions after MRI and the surgical observations were excellent for 37 patients. In one case MRI showed a false image of tear of the supra spinatus m. on its anterior edge. This was due to a bad knowledge of the anatomy of the muscle and tendon and to a poor orientation of the frontal cut plane. This study was complete with MRI and anatomic study of 12 non embalmed cadaveric shoulders. The results showed that MRI was very sensitive (0.93) and specific (0.94) for the diagnosis of rotator cuff tears. MRI allowed also to show partial tears of the tendons of the rotator cuff. The authors propose a MRI classification of cuff lesions which permits to establish a good surgical planning. PMID- 8483151 TI - [Postero-superior glenoid impingement. Another impingement of the shoulder]. AB - An impingement occurring between the deep side of the supraspinatus tendon and the postero-superior edge of the glenoid cavity was evidenced in a young sports thrower presenting with a partial tear of the deep side of the tendon. This impingement occurred when the arm was in abduction-retropulsion and in forced lateral rotation. It was visualized on arthroscopy. The semiology was mixed, including signs of anterior instability and cuff impairment. The possible causes of partial tears of the deep side of the supraspinatus are discussed: sub acromial impingement of NEER, anterior instability with secondary impingement, postero-superior glenoid impingement. PMID- 8483152 TI - [Acute bilateral parotitis. Isolated prodrome to anaphylactoid shock following injection of iodinated contrast media]. AB - We report a peculiar case of radiocontrast induced anaphylactoid shock following an intravenous pyelography, which was announced by an hyperacute bilateral parotid enlargement as the sole prodrome. From a review of the literature, two clinical presentation of iodide-induced sialadenitis are individualized according to their pathogenesis. In patients with normally functioning kidneys, the occurrence of a sialadenitis after a short delay (5 minutes to 24 hours) evokes an anaphylactoid mechanism. In patients with renal function impairment, the role played by extrarenal excretory pathways of iodinated compounds and especially the salivary glands, results in a delayed onset (1 to 5 days) of the sialadenitis due to an effect of toxicity. PMID- 8483153 TI - [Consensus Conference. Acute cerebral ischemia in adults. Study strategies. Palais des Congres. 1992 November 2 and 3]. PMID- 8483154 TI - Aplastic crisis due to human parvovirus (B19) as an initial presentation of hereditary spherocytosis. PMID- 8483155 TI - Case records of the University of Mississippi Medical Center. Adenocarcinoma of the pancreas. PMID- 8483156 TI - Reform revisited. PMID- 8483157 TI - Waiting for the windfall. PMID- 8483158 TI - Relationship between G + C in silent sites of codons and amino acid composition of human proteins. AB - We have investigated the relationship between the G + C content of silent (synonymous) sites in codons and the amino acid composition of encoded proteins for approximately 1,600 human genes. There are positive correlations between silent site G + C and the proportions of codons for Arg, Pro, Ala, Trp, His, Gln, and Leu and negative ones for Tyr, Phe, Asn, Ile, Lys, Asp, Thr, and Glu. The median proteins coded by groups of genes that differ in silent-site G + C content also differ in amino acid composition, as do some proteins coded by homologous genes. The pattern of compositional change can be largely explained by directional mutation pressure, the genetic code, and differences in the frequencies of accepted amino acid substitutions; the shifts in protein composition are likely to be selectively neutral. PMID- 8483159 TI - Characterization of the length polymorphism in the A + T-rich region of the Drosophila obscura group species. AB - In the twelve Drosophila obscura group species studied, belonging to the affinis, obscura, and pseudoobscura subgroups, the mitochondrial DNA length ranges from 15.8 to 17.2 kb. This length polymorphism is mainly due to insertions/deletions in the variable region of the A + T-rich region. In addition, one species (D. tristis) possess a tandem duplication of a 470-bp fragment that contains the replication origin. The same duplication has occurred at least twice in the Drosophila evolutionary history due to the fact that the repetition is analogous to repetitions found in the four species of the D. melanogaster complex. By comparing the nucleotide sequence of the conserved region in D. ambigua, D. obscura, D. yakuba, D. teissieri, and D. virilis, we show the presence of a secondary structure, likely implied in the replication origin, which could favor the generation of this kind of duplications. Finally, we propose that the high A and T content in the variable region of the A + T-rich region favors the formation of less-stable secondary structures, which could explain the generation of minor insertion/deletions found in this region. PMID- 8483160 TI - The product of the Drosophila melanogaster segment polarity gene armadillo is highly conserved in sequence and expression in the housefly Musca domestica. AB - Segmental pattern in Drosophila melanogaster is set up via a set of cell-cell interactions mediated by the products of the segment polarity genes. Among these is the armadillo gene, whose product seems to be required for the reception of an intercellular signal encoded by the wingless gene. As part of our effort to relate the structure of the armadillo protein to its function within the cell, we have examined the evolutionary conservation of the armadillo gene during insect evolution. We have cloned the armadillo gene from the housefly, Musca domestica, which diverged from Drosophila 100 million years ago. The Musca protein is 97.5% identical to that in Drosophila, while the noncoding sequences have diverged extensively. This remarkable degree of conservation at the protein level is mirrored in the expression pattern of the armadillo protein. Antibodies against the Drosophila protein cross-react with a Musca protein of the appropriate size. We have also used these antibodies to show that the Musca armadillo protein has a pattern of expression in larval and adult tissues similar to that of Drosophila armadillo. We discuss the implications of conservation of structure and expression for the cellular role of the armadillo protein and its mammalian homologs. PMID- 8483161 TI - Functional conservation of a glucose-repressible amylase gene promoter from Drosophila virilis in Drosophila melanogaster. AB - Previous studies have demonstrated that the expression of the alpha-amylase gene is repressed by dietary glucose in Drosophila melanogaster. Here, we show that the alpha-amylase gene of a distantly related species, D. virilis, is also subject to glucose repression. Moreover, the cloned amylase gene of D. virilis is shown to be glucose repressible when it is transiently expressed in D. melanogaster larvae. This cross-species, functional conservation is mediated by a 330-bp promoter region of the D. virilis amylase gene. These results indicate that the promoter elements required for glucose repression are conserved between distantly related Drosophila species. A sequence comparison between the amylase genes of D. virilis and D. melanogaster shows that the promoter sequences diverge to a much greater degree than the coding sequences. The amylase promoters of the two species do, however, share small clusters of sequence similarity, suggesting that these conserved cis-acting elements are sufficient to control the glucose regulated expression of the amylase gene in the genus Drosophila. PMID- 8483162 TI - Nucleotide divergence of the rp49 gene region between Drosophila melanogaster and two species of the Obscura group of Drosophila. AB - A 2.1-kb SstI fragment including the rp49 gene and the 3' end of the delta serendipity gene has been cloned and sequenced in Drosophila pseudoobscura. rp49 maps at region 62 on the tip of chromosome II of this species. Both the coding and flanking regions have been aligned and compared with those of D. subobscura. There is no evidence for heterogeneity in the rate of silent substitution between the rp49 coding region and the rate of substitutions in flanking regions, the overall silent divergence per site being 0.19. Noncoding regions also differ between both species by different insertions/deletions, some of which are related to repeated sequences. The rp49 region of D. pseudoobscura shows a strong codon bias similar to those of D. subobscura and D. melanogaster. Comparison of the rates of silent (Ks) and nonsilent (Ka) substitutions of the rp49 gene and other genes completely sequenced in D. pseudoobscura and D. melanogaster confirms previous results indicating that rp49 is evolving slowly both at silent and nonsilent sites. According to the data for the rp49 region, D. pseudoobscura and D. subobscura lineages would have diverged some 9 Myr ago, if one assumes a divergence time of 30 Myr for the melanogaster and obscura groups. PMID- 8483163 TI - Adaptive evolution in the rat olfactory receptor gene family. AB - Comparison of DNA sequences of the rat (Rattus norvegicus) olfactory receptor gene family revealed an unusual pattern of nucleotide substitution in the gene region encoding the second extracellular domain (E2) of the protein. In this domain, nonsynonymous nucleotide differences between members of this subfamily that caused a change in amino acid residue polarity were over four times more frequent than nonsynonymous differences that did not cause a polarity change. This nonrandom pattern of nucleotide substitution is evidence of past directional selection favoring diversification of the E2 domain among members of this subfamily. This in turn suggests that E2 may play some important role in the functions unique to each member of the olfactory receptor family, and that it may perhaps be an odorant binding domain. PMID- 8483164 TI - Evolution of avian metallothionein: DNA sequence analyses of the turkey metallothionein gene and metallothionein cDNAs from pheasant and quail. AB - The turkey metallothionein gene (tkMT) was isolated from a phage lambda-turkey genomic DNA library by virtue of high identity with chicken MT cDNA. The nucleotide sequences of the proximal 240 bp of the 5'-flanking region, of each of the three exons, and of the intron/exon boundaries were determined. Comparisons of the nucleotide sequences of the tkMT and cMT genes revealed (1) absolute conservation of intronic DNA immediately flanking each respective intron/exon boundary, (2) high conservation (95.6%) of exonic DNA encoding translated regions of the mRNA, and (3) high conservation (95%) of exonic DNA encompassing the putative transcription start point and polyadenylation signals. Sequence comparisons of the tkMT and cMT promoters regions near the TATA box revealed that both promoters contain a highly conserved proximal metal-responsive enhancer (MRE enhancer) motif. The deduced amino acid sequence (63 amino acids) of tkMT was identical with that of cMT. In order to further explore the degree of conservation of the protein coding regions of avian MT genes, partial MT cDNAs from turkey, quail (qMT), and pheasant (pMT) were amplified using the reverse transcriptase-polymerase chain reaction (RT-PCR) and primers corresponding to the amino- and carboxyl-terminal coding regions of cMT mRNA. RT-PCR reaction products were cloned and the DNA sequences of multiple cDNA clones from each species were determined. The results suggest the existence of a single MT mRNA in zinc-treated liver from turkey and pheasant and the existence of a major and possibly a minor MT mRNA in quail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483165 TI - Tempo and mode of mitochondrial DNA evolution in vertebrates at the amino acid sequence level: rapid evolution in warm-blooded vertebrates. AB - By using complete sequence data of mitochondrial DNAs, three Markov models (Dayhoff, Proportional, and Poisson models) for amino acid substitutions during evolution were applied in maximum likelihood analyses of mitochondrially encoded proteins to estimate a phylogenetic tree depicting human, cow, whale, and murids (mouse and rat), with chicken, frog, and carp as outgroups. A cow/whale clade was confirmed with a more than 99.8% confidence level by any of the three models, but the branching order among human, murids, and the cow/whale clade remained uncertain. It turned out that the Dayhoff model is by far the most appropriate model among the alternatives in approximating the amino acid substitutions of mitochondrially encoded proteins, which is consistent with a previous analysis of a more limited data set. It was shown that the substitution rate of mitochondrially encoded proteins has increased in the order of fishes, amphibians, birds, and mammals and that the rate in mammals is at least six times, probably an order of magnitude, higher than that in fishes. The higher evolutionary rate in birds and mammals than in amphibians and fishes was attributed to relaxation of selective constraints operating on proteins in warm blooded vertebrates and to high mutation rate of bird and mammalian mitochondrial DNAs. PMID- 8483166 TI - A protein alignment scoring system sensitive at all evolutionary distances. AB - Protein sequence alignments generally are constructed with the aid of a "substitution matrix" that specifies a score for aligning each pair of amino acids. Assuming a simple random protein model, it can be shown that any such matrix, when used for evaluating variable-length local alignments, is implicitly a "log-odds" matrix, with a specific probability distribution for amino acid pairs to which it is uniquely tailored. Given a model of protein evolution from which such distributions may be derived, a substitution matrix adapted to detecting relationships at any chosen evolutionary distance can be constructed. Because in a database search it generally is not known a priori what evolutionary distances will characterize the similarities found, it is necessary to employ an appropriate range of matrices in order not to overlook potential homologies. This paper formalizes this concept by defining a scoring system that is sensitive at all detectable evolutionary distances. The statistical behavior of this scoring system is analyzed, and it is shown that for a typical protein database search, estimating the originally unknown evolutionary distance appropriate to each alignment costs slightly over two bits of information, or somewhat less than a factor of five in statistical significance. A much greater cost may be incurred, however, if only a single substitution matrix, corresponding to the wrong evolutionary distance, is employed. PMID- 8483167 TI - Pediatric coefficients for TRISS analysis. AB - We computed regression coefficients for TRISS analysis for all 4271 pediatric patients (aged 1 through 14 years) with complete data from the Major Trauma Outcome Study. We then compared predicted pediatric and adult TRISS survival probability norms. There were no statistically significant differences in the predicted and actual numbers of survivors using either norm. Differences in discrimination and reliability between the two norms were minimal. The study confirmed that the TRISS adult blunt norm is highly discriminating and reliable in predicting survival probabilities for pediatric patients. Given that both norms were equally good predictors, and the importance of a consistent system to evaluate trauma care, the authors recommend the continued use of the adult blunt trauma norm for estimating survival probability in children. PMID- 8483168 TI - Emergency department thoracotomy in children: rationale for selective application. AB - Although emergency department (ED) thoracotomy is performed only in selected adult trauma victims, it continues to be widely used in children. To evaluate if use of this liberal policy is justified in children, the charts of 23 pediatric trauma victims who underwent ED thoracotomy at our institution in the past 5 years were reviewed. Mechanism of injury was blunt trauma in 65% and penetrating injury in 35%. Optimal field care was provided, with the majority (74%) of these patients having had intubation and vascular access achieved in the field and transported within 10 minutes to the trauma center. Thoracotomy and open cardiac massage were performed within 5 minutes of arrival in the ED. Despite this aggressive management, only one child (4.4%) survived to discharge, although transient restoration of spontaneous circulation (RSC) was achieved in four (17.4%) children. There were no survivors in the blunt trauma group. All patients with penetrating trauma who had no vital signs in the field died. The cost of ED thoracotomy was $2,740 +/- $214; however, the total hospitalization charges per patient averaged $14,848 +/- $1,724. Forty-six percent of total charges were reimbursed, and financial loss to the hospital per patient was $6,448 +/- $1,441. This study demonstrates that children who arrive at the ED following blunt or penetrating trauma with no cardiac rhythm are unsalvageable and should not undergo ED thoracotomy. The burden of unreimbursed care for this procedure is not trivial. Indications for ED thoracotomy in pediatric trauma victims should therefore be the same as those currently used for adult trauma victims. PMID- 8483169 TI - Thoracic trauma in children. AB - Thirty-seven children were admitted for the treatment of thoracic injuries during a 15-year period. Two thirds suffered blunt trauma. Of these children with blunt injuries, three quarters were male, with a median age of 6 years. Half of all victims of blunt trauma were between the ages of 4 and 6 years, and most were involved in motor vehicle crashes. Thirteen children (35%) were victims of penetrating trauma. Sixty-nine percent were male. The median age was 13 years, with 9 of 13 patients in their teenage years. Injuries were evenly distributed between stab and gunshot wounds. Eight of the 37 patients (22%) required thoracotomy. Fourteen had associated intra-abdominal injuries. Twelve of these patients had injuries that required exploratory laparotomy and two were managed expectantly. There were 27 patients with lung injuries, three quarters of whom were managed with tube thoracostomy alone. Seven children suffered injuries that resulted in their deaths. Six had been struck by a motor vehicle. Four of these six died of closed head injuries. The overall mortality of patients with blunt trauma was 25%. PMID- 8483170 TI - Survival determinants in patients undergoing emergency room thoracotomy for penetrating chest injury. AB - Survival determinants were examined in patients undergoing ERT-PCI who were admitted to the Surgical Intensive Care Unit (SICU) between January 1, 1982 and August 1, 1991. Twenty-one of 290 patients undergoing ERT-PCI (aged 14-36 years) were admitted to the SICU. Of the 21, nine survived to discharge with normal neurologic function. Four survived with neurologic impairment. Eight expired 1 to 12 days after admission. The ERT was done immediately upon hospital arrival or subsequently in the Emergency Department for impending arrest despite resuscitation. All survivors had a pulse or blood pressure either in the field or upon arrival in the ER. Seven of nine who survived neurologically intact were awake on arrival in the ER, the other two were moving their extremities. One of four who survived with neurologic impairment was awake on arrival; three were comatose. Five of the eight who died were in full arrest in the field and upon arrival in the ER. Two of these patients were brain dead shortly after SICU arrival. All survivors had vital signs either in the field or on ER arrival. Patients with penetrating chest wounds without vital signs in the field who do not recover vital signs by hospital arrival do not benefit from emergency room thoracotomy. Evidence of mentation in the field or on arrival may predict ultimate neurologic outcome of survivors. PMID- 8483171 TI - Secondary survey following blunt trauma: a new role for abdominal CT scan. AB - Computerized tomographic (CT) scanning for blunt abdominal trauma has focused on initial emergency department evaluation. At our institution, CT scanning is often used on a delayed basis for unexplained drops in hematocrit, investigation of bony injuries, or subtle abdominal findings. We reviewed 268 such scans. Over 32 months, 487 CT scans were done for 5258 blunt trauma admissions. Of these scans, 268 (55%) were done 8-72 hours after admission on patients under observation. Scanning indications were a falling hematocrit (67%), associated injuries (28%), and abdominal tenderness (5%). Fifty of the 268 scans (19%) were positive for intra-abdominal abnormalities. Pleural effusions were seen in 82 (31%). Sixteen abdominal explorations were done. There was no difference in the pre-scan hematocrit drop in patients with normal scans (6.6%), positive scans (6.8%), and those who were explored (6.4%). There was one false positive (0.4%) and two false negative scans (0.8%). Conclusions. (1) A significant number of occult injuries, some life threatening, are detected by delayed CT scans. (2) Hematocrit drop under observation is not a good predictor of occult intra-abdominal injury. (3) Delayed CT scanning for occult abdominal injury is cost effective. PMID- 8483172 TI - The etiology of missed cervical spine injuries. AB - Missed or delayed diagnosis of cervical spine (C-spine) injuries may lead to extension of those injuries and subsequent preventable mortality or morbidity. Previous reports examining the incidence of missed C-spine injuries have not determined the nature of the causal clinical errors made or the extent to which these errors are avoidable. This study was undertaken to (1) determine the incidence of delayed or missed diagnosis of C-spine injuries and the consequences of those missed injuries; (2) define the clinical errors leading to the delays; and (3) to determine if these errors are the result of fundamental problems or a lack of advanced diagnostic skills or equipment. Between August 1985 and February 1991, 32,117 trauma patients were admitted to one of the six trauma centers in San Diego county. Cervical spine injuries were identified in 740 patients and the diagnosis was delayed or missed in 34 patients (4.6%). Ten of the 34 patients (29%) developed permanent sequelae as a result of these delays. The single most common error was the failure to obtain an adequate series of C-spine roentgenograms. Delayed diagnosis could have been avoided in at least 31 of 34 injuries by the appropriate use of a standard three-view C-spine series and careful interpretation of those roentgenograms. Patients at risk for C-spine injuries require a technically adequate three-view C-spine series and skilled radiographic interpretation. Cervical spine precautions should be maintained, particularly in high risk patients, until appropriate and expert review of the cervical spine roentgenograms can be obtained. PMID- 8483173 TI - Combined penetrating rectal and genitourinary injuries: a challenge in management. AB - The standard management of penetrating rectal trauma consists of perioperative antibiotics, a diverting colostomy, and presacral drainage. While providing optimal results in isolated rectal trauma, this management scheme is inadequate in combined penetrating rectal and genitourinary (GU) tract injuries. A review of more than 200 cases of penetrating rectal trauma from our institution over a 13 year period identified 17 concomitant GU tract injuries (13 bladder, three urethral, and one ureteral injury). Complications consisted of pelvic, suprapubic, or subphrenic abscesses in 3 of 17 cases (18%), rectovesical or rectourethral fistulae in 24%, chronic urinary tract infections in 18%, bladder stones in 12%, and the development of urethral strictures in 12% of patients. Factors implicated in their pathogenesis included failure to perform presacral drainage, distal rectal washout, and rectal wound repair; prolonged suprapubic drainage; and failure to separate the rectal and GU tract wounds. Careful debridement of all necrotic tissue, urinary and fecal diversion, tension-free wound closure with well-vascularized tissue, and adequate drainage and separation of the injured sites with well-vascularized tissue such as omentum should reduce the high incidence of rectourethral and rectovesical fistulae from combined rectal-GU tract trauma. Therapeutic recommendations for individualized treatment are presented. PMID- 8483174 TI - Lidocaine versus diphenhydramine for anesthesia in the repair of minor lacerations. AB - This prospective study compared the effectiveness of 1% diphenhydramine with 1% lidocaine for local anesthesia in repair of minor skin lacerations in adults with simple linear lacerations treated at our Emergency Department. Wounds were anesthetized with either lidocaine or diphenhydramine according to a random numbers table. Ninety-nine patients were included in the final analysis (51 received lidocaine; 48 diphenhydramine). Patients and physicians rated the pain of injection and suturing using a standard visual analog scale. Univariate and multivariate linear models were used on rank transformed scores of the patient and physician ratings of injection and suturing with p < 0.05 considered statistically significant. According to patient rating lidocaine was less painful for injection than diphenhydramine, with a statistically significant difference between the two anesthetics (p = 0.0017). There was no statistically significant difference in pain rating by physicians between the two anesthetics (p > 0.05). Pain with suturing was rated as minimal for both lidocaine and diphenhydramine with no statistically significant difference in the effectiveness according to either patients or physicians (p > 0.05). Lidocaine injection appears to hurt less than diphenhydramine injection according to the patients. Pain of suturing corresponding to anesthetic effectiveness appears to be equivalent for lidocaine and diphenhydramine according to both physicians and patients. Although diphenhydramine should not be substituted for lidocaine, it appears to be a viable alternative in the management of patients with allergy to amides or extremely large lacerations in which a maximum of amide anesthetic has been used. PMID- 8483175 TI - Infection in minor gunshot wounds. AB - Of the 3684 patients enrolled in our study, 3390 were available for follow-up, of which 62 patients developed wound infections related to minor gunshot wounds (1.8%). Of these patients, all sustained entry/exit-type wounds while 60% of these patients sustained more than one injury. Complications were more likely to occur when a prolonged period occurred between the time of injury and the initial treatment. The development of infection in minor gunshot wound injuries is an unusual occurrence when these injuries are limited to the soft tissue structures. Additionally, wound debridement and antibiotics are often unnecessary in minor uncomplicated gunshot wounds, but may be beneficial in patients who have sustained multiple injuries, gross wound contamination, significant tissue devitalization, large wounds, or delay in treatment. PMID- 8483176 TI - Baseball bat assault injuries. AB - The baseball bat, according to Baltimore City police crime statistics, is a commonly used weapon. To assess the severity of injuries inflicted by this modern day club, we retrospectively reviewed 75 charts of patients treated at the University of Maryland Medical Systems Hospital for baseball bat injuries from January 1990 through July 1991. Multisystem trauma was documented, with craniocerebral injury being the most frequent and the most frequent cause of death. Of the victims struck on the head, 26% sustained an intracranial hemorrhage. In our series, the history of loss of consciousness and the Glasgow Coma Scale score failed to reliably identify the patients with serious injuries. Seventeen percent of our patients with intracranial hemorrhages had both a negative or uncertain history of loss of consciousness and a normal Glasgow Coma Scale score on arrival. PMID- 8483177 TI - Outcome of arterial repairs in 23 consecutive patients at the ICRC-Peshawar hospital for war wounded. AB - Arterial injuries represent a formidable challenge to surgeons working in war zone conditions. A series of 23 consecutive patients with combat wounds from the Afghan conflict with acute arterial injury were treated at the ICRC hospital in Peshawar. The mean injury-treatment delay (lag time) was 34 hours, with 14 of the 23 patients (60%) treated more than 12 hours after injury. The overall amputation rate was 65%, but only 22% for patients revascularized within 12 hours of injury and 93% for those undergoing surgery after 12 hours. This was a highly significant statistical difference (Chi-square > 13.0, p < 0.005). We recommend attempting revascularization procedures only in patients seen within 12 hours of sustaining a military-type injury to an artery in an extremity. PMID- 8483178 TI - The effect of secondary insults on mortality and long-term disability after severe head injury in a rural region without a trauma system. AB - Outcome after head injury appears to be adversely affected by secondary insults such as hypoxia or hypotension. Previous work examining the influence of these secondary insults on outcome has originated from urban environments with organized systems of trauma care. We hypothesized that secondary insults would be more frequent and that outcome of severe head injury would be worse in a rural region without a trauma system. To validate these hypotheses we retrospectively reviewed the course and outcome of all patients admitted to the Medical Center Hospital of Vermont with severe head injuries between 1980 and 1985. A cohort of 170 patients was assigned to one of two groups: group I had neither hypotension nor hypoxia at the time of admission; group II had either hypotension or hypoxia at the time of admission. The groups were similar in terms of demographics, incidence of mass lesions, frequency of craniotomy, and incidence of intracranial hypertension. Only 23% of group II patients made a good recovery compared with 56% of group I patients (p < 0.01). The mortality rate of group II patients was twice that of group I patients (66% vs. 33%; p < 0.01). When compared with data provided by the National Trauma Coma Data Bank from urban areas with trauma systems, there was no difference in outcome of patients similarly grouped according to the presence or absence of secondary insults between Vermont's rural cohort and the urban cohort. We conclude that hypotension and hypoxia adversely effect the outcome of severe head injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483179 TI - Complete dislocation of the knee without disruption of both cruciate ligaments. AB - Complete dislocation of the knee is recognized to be an extremely severe injury, representing one of the few true orthopedic emergencies. There is major trauma to the ligaments, capsule, and tendons, with a high incidence of associated damage to the popliteal artery and peroneal nerve. Resulting disability can be great, reflected by pain, stiffness, or instability of the knee; neurologic deficits in the foot and ankle; and even amputation if the vascular injury is not addressed promptly. Most accounts of knee dislocations in the literature have suggested that disruption of both cruciate ligaments is necessary for a complete dislocation to occur. This consensus is based on clinical observations and some laboratory investigations of ligament failure patterns. This report presents four cases of complete tibiofemoral knee dislocation without disruption of both cruciate ligaments. We also review the literature on knee dislocations with an emphasis on the biomechanics of soft tissue restraints about the knee and analyze how sufficient laxity can occur, with one cruciate ligament remaining intact, to allow for complete knee dislocation. PMID- 8483180 TI - Treatment of large bone defects with the Ilizarov technique. AB - Between 1985 and 1990 we treated 11 large segmental bone defects (average 6.7 cm) in ten patients with the Ilizarov technique. Open fractures, type III according to Gustilo, represented the largest group (8 of 11 cases). The average delay before the Ilizarov technique was initiated was 8.9 months. The external fixator was usually maintained for 1 year. Bone regeneration was obtained in every case. Consolidation was not fulfilled with this technique in three cases. The complications observed were one refracture, four leg-length discrepancies (average 1.5 cm), and five axial deformities exceeding 5 degrees. No pin-track infection was observed. In our limited series of four type IIIC open fractures treated by the Ilizarov technique, no patients required amputation. The Ilizarov technique is particularly useful in the treatment of large bone defects, without major complications, especially if there is an adequate initial debridement. PMID- 8483181 TI - First experience and complications with the long Gamma nail. AB - Treatment of proximal femoral fractures is difficult. A retrospective analysis of 92 patients treated with a custom-made extended gamma nail with a mean follow up of 4 months is presented. The early results of this new method are promising. The indications for the use of the long gamma nail were intertrochanteric fractures with extension to the subtrochanteric region, imminent and pathologic fractures of the intertrochanteric and subtrochanteric region, mostly in elderly patients, proximal femoral fractures, and combination injuries in multiple trauma patients and delayed unions. In 67 cases the patients were primarily treated with a long Gamma nail. In 25 cases the nail was used after the failure of initial treatment. Complications occurred in 32 patients; however, 88 patients were able to walk at the end of the study. The advantage of this new method is that with a closed surgical technique full weight bearing directly after the operation is achieved. The long Gamma nail provides a procedure by which most complex fractures in the proximal femur can be managed. PMID- 8483182 TI - Peripheral nerve elongation with tissue expansion techniques. AB - Elongation of peripheral nerves would facilitate the repair of peripheral nerve injuries. The purpose of this study was to determine the efficacy of nerve expansion and the effect of different levels of intraluminal expander pressure upon nerve conduction. A 2-mL Silastic expander was placed under one sciatic nerve of adult male rats. The other nerve served as a control. Electroneuromyography (ENMG) was done at the time of initial expansion in seven animals. At 40 mm Hg expansion pressure a significant change in latency was found with an increase of 17% +/- 5%. Expansion was carried out for 14 days in two groups of seven rats, group I at 20 mm Hg and group II at 40 mm Hg. Length gain on the expanded side was 30% in group I and 40% in group II. No significant changes in latency or velocity were found after expansion. We conclude that nerves can be expanded at low pressures with no significant conduction changes but long-term recovery of histologic changes needs to be evaluated. PMID- 8483183 TI - Vicryl mesh for repair of severely injured kidneys: an experimental study. AB - We evaluated the efficacy of wrapping the kidney with semi-elastic Vicryl mesh for control of hemorrhage and preservation of renal function following grade III kidney lacerations (shattered kidney) in dogs in which nephrectomy was indicated clinically. Wrapping of fragmented kidneys resulted in prompt, sustained hemostasis and reapposition of the renal parenchyma. At an average of 80 days after injury the renal lacerations were well healed. The Vicryl mesh had been fully reabsorbed and there was considerably less scar tissue at the site of parenchymal rupture and neither perirenal or intrarenal abscess nor hematoma was found, grossly or microscopically. Among 12 dogs with grade III kidney lacerations, the mean ratio of the effective renal plasma flow (ERPF) in the affected kidney to the ERPF in the uninjured contralateral kidney was 0.53 +/- 0.22. The mean ratio of creatinine clearance of the injured kidney to that of the uninjured contralateral kidney was 0.41 +/- 0.23. Changes in the serum renin levels were not statistically significant following injury. Our results seem to confirm that simple and rapid surgical treatment of severely shattered kidneys using semi-elastic Vicryl mesh is possible. The method may also be suitable for uncontrollable bleeding during nonextirpative kidney surgery. PMID- 8483184 TI - A rabbit model of inhalation injury. AB - In the course of developing a model of inhalation injury, the relationship between the severity of pulmonary injury and specific techniques and doses of smoke exposure was examined in pairs of rabbits simultaneously exposed to smoke. In group I (5 pairs), one animal in each pair was exposed to smoke with a breath hold (BH) at the end of each exposure; the second animal received an exposure producing the same level of carboxyhemoglobin without BH. In group II (6 pairs), both animals were exposed to 25 units of smoke simultaneously, with BH. In group III (3 pairs), one animal received a 20-unit exposure and the other a 25-unit exposure, both with BH. In group IV, 9 animals received 25-unit exposures with BH and were observed for 4 days. Groups V and VI served as controls. Smoke exposure with BH regularly produced severe injury in terms of decreased PaO2 and histopathologic changes, while exposure without BH did not, despite high levels of carboxyhemoglobin after smoke inhalation. The mean differences in percent residual PaO2 (PaO2 at 48 hours x 100/pre-injury PaO2) and in extravascular lung water (EVLW) at 48 hours within pairs of animals receiving 25 units with BH were 12.3% +/- 5.33%, and 0.271 +/- 0.157 mL/g, respectively. Histologic findings such as necrotic tracheobronchitis with pseudomembrane were consistently present. No differences were observed between animals receiving exposure of 20 and 25 units. During the 4 days of observation, three animals in group IV died. PaO2 was lowest on the second day and rose thereafter in all surviving animals except in one that had massive pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483185 TI - Effect of thermal injury and sepsis on neutrophil function. AB - Burn injury and sepsis have been repeatedly demonstrated to impair the function of circulating (blood) neutrophils. As a result of the difficulty in harvesting and purifying neutrophils from the burn wound, there have been minimal investigations to date on the effect of burn injury and sepsis on the function of neutrophils which have reached the wound. We utilized a sponge matrix model in order to obtain neutrophils from burned and burned-infected rats. Despite having a higher concentration of neutrophils in the blood, both the burned and burned infected rats were noted to have a decreased number of neutrophils infiltrating the sponge compared with the controls (1.91 +/- 0.30 x 10(6), 2.31 +/- 0.47 x 10(6), and 4.82 +/- 0.64 x 10(6) neutrophils per sponge, respectively). Blood neutrophils from both the burned and burned-infected rats had a greater chemiluminescence capacity than neutrophils from the control group (p < 0.0001). This enhanced capacity was not present with sponge neutrophils obtained from the burned-infected group. The diminished capacity may have been the result of a decreased concentration of prostaglandin E in the sponge fluid of the burned infected rats compared with that of the burned or control rats (52 +/- 9, 135 +/- 15, and 114 +/- 13 pg/mL of sponge fluid, respectively). PMID- 8483186 TI - Comparison of intraosseous, central, and peripheral routes of crystalloid infusion for resuscitation of hemorrhagic shock in a swine model. AB - Venous access is often a clinical dilemma in severely hypovolemic children. This study compares fluid resuscitation by central vein, peripheral vein, and the intraosseous route in a hemorrhagic shock model. Hampshire piglets were bled to a mean arterial pressure of 30 mm Hg. This level of shock was sustained for 30 minutes. Resuscitation was carried out with normal saline delivered at 50 mL/min by a manual pressure of 450-475 mm Hg over the ensuing 20 minutes. Bone marrow from two intraosseous-infused animals was harvested immediately after the study for histologic examination. The hemodynamic response to crystalloid resuscitation was comparable among the three groups. There was no significant difference in mean arterial pressure, central venous pressure, cardiac output, pulmonary capillary wedge pressure, mixed venous oxygen saturation, or arterial oxygen saturation. Histologically, cellular washout and necrosis were found in bone marrow immediately adjacent to the intraosseous needle infusion site. For fixed rate infusion, intraosseous crystalloid resuscitation is as efficacious as that delivered by peripheral or central venous routes in reversing hemorrhagic shock. PMID- 8483187 TI - Systemic fluoride toxicity in a child with hydrofluoric acid burns: case report. AB - We report the case of a 14-month-old child with hydrofluoric acid burns who suffered cardiac arrest in association with profound hypocalcemia and hyperfluoridemia. Successful treatment included topical, subeschar, and intravenous calcium gluconate administration. PMID- 8483188 TI - Hemobilia due to gallbladder contusion following blunt trauma--sonography and CT scanning for early detection: case report. AB - Gallbladder injury following blunt trauma is rare and early diagnosis is difficult when it is associated with other injuries. Clinical symptoms and signs alone are not necessarily helpful in diagnosing such cases. However, modern diagnostic imaging procedures such as ultrasonography and CT scanning are valuable for investigating possible gallbladder injuries. Patients with blunt trauma should be carefully examined by US and CT for early detection and treatment of gallbladder injuries. PMID- 8483189 TI - Gunshot wound to the area of a congenitally absent internal carotid artery: case report. AB - We present the case of a patient who sustained a gunshot wound in very close proximity to the left external carotid artery. The bullet was located exactly over the typical location of the internal carotid artery. Total agenesis of the internal carotid artery, a rare anomaly, was differentiated from thrombosis of the internal carotid artery. PMID- 8483190 TI - The post-cardiac injury syndrome following blunt chest trauma: case report. AB - The case of a 53-year-old man is reported in which the patient developed post cardiac injury syndrome 2 weeks after blunt trauma to the thorax. The patient failed to respond adequately to ibuprofen but improved on corticosteroids. He suffered relapses 8 and 15 months after the original injury following reductions in the corticosteroid dosage. The patient at last follow-up had been asymptomatic for over 4 years. PMID- 8483191 TI - Balloon tamponade for liver injuries: case report. AB - A tamponade device for control of refractory liver bleeding is occasionally indicated. This report documents to our knowledge the first reported use of Foley catheter balloon tamponade for severe liver injury. PMID- 8483192 TI - Upper extremity salvage with free ulnar forearm flap from the amputated part: case report. AB - Preservation of a functional level of amputation in cases of nonreplantable upper extremity amputation injury can be accomplished utilizing spare-parts technology. A case is presented in which a nonreplantable arm amputated at the mid-humeral level was used for a free ulnar forearm flap to preserve bone level and secure stable coverage. PMID- 8483193 TI - Herniation of the stomach into the pericardial sac combined with cardiac luxation caused by blunt trauma: a case report. AB - Cardiac luxation caused by blunt thoracic trauma carries a high mortality rate. We present a case of traumatic diaphragmatic rupture, in combination with herniation of the stomach into the pericardial sac, pericardial rupture, and cardiac luxation. The recent literature is reviewed and diagnostic difficulties and procedures are discussed. PMID- 8483194 TI - Combined severe myocardial and pulmonary contusion: early diagnosis with transesophageal echocardiography and management with high-frequency jet ventilation: case report. AB - We report the case of a 27-year-old patient with blunt thoracic trauma in whom transesophageal echocardiography enabled an early diagnosis of severe myocardial contusion. Conventional mechanical ventilation dramatically enhanced cardiogenic shock because of myocardial contusion, requiring increasing doses of catecholamine. High-frequency jet ventilation produced an immediate improvement in hemodynamic status, permitting a decrease in catecholamine administration. PMID- 8483195 TI - Simultaneous rupture of the patellar tendons bilaterally: case report and review of the literature. AB - Rupture of the patellar tendon is uncommon. In most cases the rupture occurs at the inferior border of the patella rather than through the midsubstance of the tendon. Bilateral ruptures are particularly rare and may occur sequentially or, as in the case reported here, simultaneously. Surgical repair is necessary to re establish the extensor mechanism and produces good results. PMID- 8483196 TI - Primary shortening followed by callus distraction for the treatment of a posttraumatic bone defect: case report. AB - The case of a 10-year-old boy is reported in which a 5-cm defect of the humerus sustained 2 months previously was treated by open reduction and external fixation followed by distraction beginning on the 20th day after surgery and continuing to the 40th day. The result was a 4-cm gain in length, with return of normal function and complete resolution of a concomitant radial nerve palsy. PMID- 8483197 TI - Rotatory dislocation of the second carpometacarpal joint: case report. AB - Isolated dorsal dislocation and rotatory dislocation of the second carpometacarpal joint is rare. A case of rotatory dislocation of this joint is presented, where reduction was blocked by entrapment of the extensor carpi radialis longus tendon in the joint. A roentgenographic technique for evaluating dislocation of carpometacarpal joints is also described. PMID- 8483198 TI - Inferior locking of the patella: a case report. AB - A 87-year-old woman with femoropatellar arthrosis sustained a fixed inferior traumatic locking of the patella with the knee in flexed position. After closed manipulation locking recurred and surgery was necessary to ensure smooth articulation. PMID- 8483199 TI - Computerized tomographic appearance of hernias of the bladder. AB - Herniation of the bladder is not uncommon and it can occur with any type of hernia in the groin. Most bladder hernias are discovered unexpectedly during herniorrhaphy, and serious complications can result from intraoperative injury to the bladder. The appearance of hernias on excretory urography and cystography has been described extensively but experience with computerized tomography (CT) has been limited. We describe the appearance of 8 bladder hernias on CT: 2 incisional, 2 femoral, 3 small direct inguinal, and 1 massive direct inguinal hernia with bladder necrosis and perforation. Appearance on CT is characteristic, and this modality may be useful for preoperative evaluation. PMID- 8483200 TI - Oral methotrexate for superficial transitional cell carcinoma of the bladder. AB - A total of 22 patients with superficial transitional cell carcinoma of the bladder, uncontrolled cystoscopically and unsuitable for or having failed intravesical therapy, received 50 mg. oral methotrexate per week for 12 months. Of the patients 7 (32%) achieved or remained in complete remission and 5 achieved a partial response, while 4 remained stable, 3 had progression and 3 were not evaluable. Patients who were still alive had a median followup of 2.5 years. Two patients with complete remission had relapse at 16 and 26.4 months, and 5 were disease-free at 34.5, 31.3, 18.6, 17.8 and 16.8 months, respectively. The methotrexate was generally well tolerated but 2 patients discontinued therapy because of dyspnea (1 subsequently died of respiratory failure that was possibly related to the methotrexate) and 1 because of persistent grade 2 mucositis. Grade 3/4 toxicities occurred in 3 patients: 1 each with reversible increases in creatinine and aspartate aminotransferase, and 1 with gastric bloating. There was little hematological toxicity. Reversible skin lesions developed in 4 patients. This oral treatment may provide an effective alternative to intravesical therapy but can be associated with severe toxicity. PMID- 8483201 TI - Late invasive recurrence despite long-term surveillance for superficial bladder cancer. AB - Superficial transitional cell carcinoma of the bladder is associated with a 15 to 70% recurrence rate within 2 years. Most recurrences are superficial. A recurrence after 2 disease-free years is unusual. A review of the tumor registry revealed 124 patients followed for superficial disease at the Veterans Administration Center in Baltimore. Of the patients 20 were identified with either stage Ta (7) or stage T1 (13) papillary transitional cell carcinoma who had completed at least 5 years of surveillance without tumor recurrence. Invasive transitional cell carcinoma of the bladder requiring cystectomy developed in 7 of these 20 patients after remaining tumor-free for 5 years (stage Ta in 4 and stage T1 in 3). All 7 patients had organ-confined disease and were alive with no evidence of disease at 18 months to 5 years after cystectomy. These results demonstrate that superficial, low grade transitional cell carcinoma of the bladder can become muscle invasive despite careful surveillance and a long dormant period. In our series yearly cystoscopy and urine cytology identified tumor recurrence before metastases developed, suggesting that long-term surveillance is required in patients with superficial bladder cancer. PMID- 8483202 TI - Pubovaginal sling for treatment of female stress urinary incontinence complicated by urethral diverticulum. AB - To evaluate the practicality of combining urethral diverticulectomy with a procedure for stress urinary incontinence, the records of 14 patients who underwent urethrodiverticulectomy during a 3-year period were reviewed. Noteworthy was that 10 patients (71%) had urinary incontinence as the chief complaint, while 8 (57%) had symptoms of stress urinary incontinence and underwent fluoroscopic urodynamic testing and the others had post-void dribbling. Of the latter 8 patients 7 (50%) demonstrated type II or type III stress urinary incontinence and 1 had a normal study. The 7 women then underwent transvaginal diverticulectomy with a concomitant pubovaginal sling. Of the diverticula 4 (57%) were true diverticula and 3 (43%) appeared to be pseudodiverticula or traction diverticula related to a previous urethral suspension. At 3 to 21 months (mean 17) all patients were cured of stress urinary incontinence. One patient exhibited detrusor instability postoperatively, which was ultimately treated with an Ingelman-Sundberg procedure. Postoperatively, 1 diverticulum recurred, for a recurrence rate of 14%. We conclude that the presence of a urethral diverticulum does not compromise successful repair of associated stress urinary incontinence when the pubovaginal sling procedure is used. PMID- 8483203 TI - Radical retropubic prostatectomy and postoperative adjuvant radiation for pathological stage C (PcN0) prostate cancer from 1976 to 1989: intermediate findings. AB - Between 1976 and 1989, 114 patients undergoing radical retropubic prostatectomy and bilateral pelvic lymph node dissection for prostatic adenocarcinoma were found to have stage PcN0 lesions. Postoperative adjuvant radiation therapy without hormonal treatment was given to 95 of these patients (83%): 26 (27%) with stage C1, 37 (39%) with stage C2 and 32 (34%) with stage C3 disease. The median radiation dose was 45 Gy. given at 180 cGy. daily. Median followup was 4.4 years (range 1.4 to 13.3). The overall 5 and 10-year actuarial rates for the patients were 94% and 70%, respectively. Disease-specific 5 and 10-year actuarial survival rates were 99% and 78%, respectively. At 5 and 10 years the chance of clinical recurrence was estimated as 6% and 13%, respectively, and the chance of recurrence (clinical or indicated by prostate specific antigen levels) was estimated to be 34% and 46%, respectively. Patients with high Gleason scores (8 to 10) and seminal vesicle involvement (stage C3) fared worst. There were 5 patients with clinical distant metastases, 1 with a clinical local recurrence and 1 with both conditions. Detectable elevation of prostate specific antigen without clinically evident recurrence was noted in 25 patients. Radiation therapy was well tolerated with minimal morbidity. Disease-specific survival and survival without clinical recurrence were improved over historical control in patients with stage PcN0 prostate cancer treated by radical prostatectomy alone. These data support a role for adjuvant radiation therapy in stage PcN0 prostate adenocarcinoma following radical prostatectomy. PMID- 8483204 TI - Efficacy of transrectal ultrasound-guided seminal vesicle biopsies in the detection of seminal vesicle invasion by prostate cancer. AB - Detection of microscopic seminal vesicle invasion with prostate cancer by transrectal ultrasound-guided seminal vesicle biopsies provides a method of evaluation that is much less subjective than digital rectal examination or imaging techniques. The accuracy of seminal vesicle biopsy is analyzed in 73 patients undergoing transrectal ultrasound-guided biopsy of 145 seminal vesicles followed by radical prostatectomy. Of 133 benign seminal vesicle biopsies 11 (8.3%) were found in the surgical specimen to have cancer involving an average of 6% of the seminal vesicle area. Of 8 seminal vesicle biopsies showing cancer adjacent to seminal vesicle epithelium 100% demonstrated seminal vesicle invasion in the surgical specimen extending for an average of 19% of the seminal vesicle area. Three biopsies exhibited cancer but no seminal vesicle epithelium; only 1 (33%) of these had seminal vesicle invasion for 5% of the seminal vesicle area. One biopsy revealed normal prostate tissue. Careful placement of bilateral biopsy sites cephalad to the prostate base (not traversing any portion of the prostate gland) is recommended. Caution should be exercised when basing treatment decisions on seminal vesicle biopsies that do not reveal seminal vesicle epithelium histologically. PMID- 8483205 TI - Adenocarcinoma of the prostate invading the seminal vesicle: definition and relation of tumor volume, grade and margins of resection to prognosis. AB - An issue relating to uniformity in pathological staging of prostate cancer that has received relatively minimal attention is that of seminal vesicle invasion. Several studies define tumor in the per-seminal vesicle soft tissue as seminal vesicle invasion, while others equate seminal vesicle invasion with tumor invading the muscular wall of the seminal vesicle. There are also controversies regarding the prognostic significance of seminal vesicle invasion compared to capsular penetration, and whether seminal vesicle invasion is a predictor of poor prognosis independent of tumor volume and grade. We evaluated 115 cases of established capsular penetration, 16 of peri-seminal vesicle invasion and 45 of seminal vesicle invasion in patients without lymph node metastases. Patients with seminal vesicle invasion had a significantly worse prognosis than those with capsular penetration; peri-seminal vesicle invasion was associated with an intermediate risk of progression. Gleason grade, surgical margins and seminal vesicle invasion were all independent predictors of progression in a multivariate analysis, whereas tumor volume was not. In patients with seminal vesicle invasion there was a trend for surgical margins and Gleason grade to predict progression; with tumor volume there was none. Our study demonstrates that the definition of seminal vesicle invasion should be restricted to tumors showing infiltration into the muscular wall of the seminal vesicle. Our study further demonstrates that when assessing the ability of new prognostic variables to predict prognosis of patients with seminal vesicle invasion, margins of resection and Gleason grade should be considered. PMID- 8483206 TI - Urinary tract infections in healthy university men. AB - Acute symptomatic urinary tract infections occurred spontaneously in healthy university men. The mean incidence was 5 symptomatic infections per 10,000 men per year. Men with symptomatic infections were older than other students (p = 0.001) and 90% were sexually active. Of 38 patients 35 (92%) responded to a single course of antimicrobial therapy. Factors implicated in other male populations, such as anatomical abnormalities, urinary tract instrumentation, bacterial prostatitis and lack of circumcision, were seldom identified. Extensive evaluation appears unnecessary for young men with bacteriuria who respond to antimicrobial therapy. PMID- 8483207 TI - Urinary immunoreactive interleukin-1 alpha and interleukin-6 in bacteriuric institutionalized elderly subjects. AB - Urinary immunoreactive interleukin-1 alpha and interleukin-6 levels were measured in specimens obtained from elderly institutionalized subjects, including 67 asymptomatic subjects (51 of whom were bacteriuric), 34 with fever from nonurinary sources, 15 with bacteriuria and 9 with symptomatic urinary infection. For bacteriuric subjects urinary interleukin-1 alpha and interleukin-6 levels were measurable in 18 (35%) and 22 (43%) asymptomatic subjects, respectively, 9 (60%) and 8 (53%) with nonurinary sources of fever, respectively, and 6 (67%) and 7 (78%) with urinary infection, respectively. For subjects without bacteriuria 1 of 16 (6.3%) who were asymptomatic and 5 (25%) with nonurinary sources of fever had measurable urinary interleukin-1 alpha, and 2 (13%) and 1 (5.3%), respectively, had measurable interleukin-6. Presence of interleukin-1 alpha or interleukin-6 was significantly associated with bacteriuria for asymptomatic and symptomatic subjects. Interleukin-1 alpha or interleukin-6 quantitative levels were lower in subjects without than with bacteriuria. Quantitative levels of interleukin-6 tended to decrease for bacteriuric subjects with symptomatic infection between acute and convalescent specimens. These observations suggest that interleukin-1 alpha and interleukin-6 are produced in association with bacteriuria in some elderly subjects. Variation in local cytokine production with time and the clinical significance of these observations require further study. PMID- 8483208 TI - Laparoscopic surgical training: effectiveness and impact on urological surgical practice patterns. AB - Urological interest in laparoscopic surgical techniques has dramatically increased during the last several years. However, the extent to which these methods are being used and the impact of training courses on clinical use are unclear. We assessed urologist practice patterns subsequent to a formal training course in urological laparoscopic surgery. On 5 dates between January and October 1991, a total of 163 urologists participated in a 2-day, university sponsored, laparoscopic surgery training seminar. Instruction consisted of 8 hours of didactic lectures including 2 live video cases, 4.5 hours of simulation and 4.5 hours in a live animal laboratory. Three months after the course the participants were mailed a questionnaire inquiring as to the interval laparoscopic surgery experience. Practice demographics, additional training, equipment availability, number of laparoscopic surgery candidates identified, percentage of overall surgical case load, patient inquiries, cases performed and complications were assessed by the questionnaire. Descriptive and correlative information was then derived from the data set. A total of 105 course participants (64%) responded to the questionnaire and 64 had engaged in some form of additional training following the course. During the 3 months since course completion respondents had identified an average of 4 candidates for laparoscopic surgery, which represented a mean of 2.5% of the total case load. Specific patient inquiries averaged less than 1 per physician within 3 months. During this same interval respondents had performed a total of 156 laparoscopic procedures (1.7 per urologist). Of the participants 45% had not performed their first case and 32% had performed more than 1 laparoscopic procedure. A total of 11 complications was reported (7.2%) and in 7 instances the surgeon was required to convert to an open approach. Veress needle placement was perceived as the most difficult aspect of the technique (22% of the respondents). Training subsequent to the course was the best predictor of clinical use. Of those who responded 88% believed that their future use of laparoscopy would increase. This survey suggests that subsequent to training, laparoscopic techniques are being rapidly and safely used by urologists. However, in the current state of development the impact of laparoscopic surgery on global urological practice patterns appears to be small. PMID- 8483209 TI - The risk of exposure to potentially contaminated body fluids in urological surgery. AB - To determine the risk of exposure to body fluids potentially contaminated with infectious organisms we instituted a prospective study of all urological procedures performed at our institution. Urological procedures were divided into 3 categories: open, cystoscopic and endoscopic surgical (transurethral resection of the prostate or bladder tumor, ureteroscopy and percutaneous procedures). We have complete data analysis on 594 consecutive patients who underwent an operation at our institution: 77 (13%) underwent an open procedure, 75 (13%) underwent an endoscopic surgical procedure and the remaining 442 (74%) underwent cystoscopic procedures. All procedures were performed by supervised house staff using universal precautions. The operating surgeon was exposed to potentially contaminated body fluids in 173 of 594 cases overall (29%). There was exposure in 17% of all open procedures, 41% of all endoscopic surgical procedures and 29% of all cystoscopic procedures. Urologists must consider themselves at high risk for exposure to potentially contaminated body fluids and take appropriate precautions. PMID- 8483210 TI - A new technique for renal biopsy: the transurethral approach. AB - An 18 gauge needle sheathed in an 8F catheter can be advanced into an upper calix through the lumen of a transurethrally placed 10F catheter and used to biopsy the renal cortex. The transurethral biopsy technique is less painful, less invasive and simpler than the open or laparoscopic approach, and it can be used as an extension of cystoscopic examination to avoid percutaneous biopsy. PMID- 8483211 TI - Incidence and management of autonomic dysreflexia and other intraoperative problems encountered in spinal cord injury patients undergoing extracorporeal shock wave lithotripsy without anesthesia on a second generation lithotriptor. AB - Spinal cord injury patients are at increased risk for urolithiasis and many will require treatment, most commonly with extracorporeal shock wave lithotripsy. New, second generation lithotripsy devices allow treatment without tub immersion, and without general or regional anesthesia for most patients. Spinal cord injury patients, with loss of sensation below the level of injury, would seem to be ideal candidates for such treatment. We present our experience with 20 consecutive spinal cord injury patients treated without anesthesia on the Medstone STS second generation lithotriptor. All patients were awake and experienced no direct sensation from the shock waves. All but 1 patient (T12 level), however, experienced autonomic dysreflexia, with significant elevations in systolic blood pressure (mean increase 44 mm. Hg, maximum 74) and diastolic blood pressure (mean increase 24 mm. Hg, maximum 61), with reflex bradycardia (mean decrease -22 beats per minute). Autonomic dysreflexia was successfully treated in this setting with short-acting sublingual nifedipine. Associated bradycardia was treated with atropine in 6 patients. Preoperative bowel preparation proved to be useful in spinal cord injury patients to maximize stone imaging and may decrease autonomic dysreflexia if this is caused by shock waves impacting on the distended bowel. Other problems included uncontrolled skeletal muscle spasms elicited by shock waves, which proved to be troublesome in maintaining patient position and stone localization. Muscle spasms were decreased with benzodiazepines. Care was also observed in spinal cord injury patients to pad all pressure points on the hard, dry treatment surfaces associated with second generation lithotriptors and, thus, prevent skin breakdown. PMID- 8483212 TI - Clean intermittent catheterization in spinal cord injury patients: a followup study. AB - A followup study on nonhospitalized spinal cord injury patients using clean intermittent catheterization was conducted to evaluate long-term clean intermittent catheterization for any genitourinary complications, and to institute and evaluate prompt management. A total of 50 patients (36 paraplegics and 14 quadriplegics) was followed for 3 months to 6.5 years (average followup 22 months). All patients had a baseline urodynamic study and renal scan before they were discharged from the hospital. Patients with a reflex bladder and sustained, high intravesical pressures (greater than 40 cm. water) were placed on anticholinergic medication to lower voiding pressures and maintain continence. Those on clean intermittent catheterization and condom drainage were also given alpha-blockers to achieve low pressure voiding and to control autonomic dysreflexia. Of 50 patients 43 (86%) acquired a total of 364 events of significant bacteriuria (10(4) or more colony-forming units per ml.) at a rate of 13.63 infections per 1,000 patient-days on clean intermittent catheterization. Subclinical symptoms for urinary tract infection were noted in 22 of the 43 patients (51%), whereas clinical symptoms for urinary tract infection were recorded in 16 of 43 (37%). These symptoms included fever in 8 patients, chills in 3, hematuria in 3 and flank pain in 2. There were 31 genitourinary complications in 21 patients noted during periodic diagnostic evaluations, with 6 classified as upper tract. Of 50 patients 4 (8%) required rehospitalization for urological problems. One patient died of questionable sepsis. Transurethral sphincterotomy was performed in 15 of the 50 patients (30%) and transurethral prostatectomy was done in 1 for multiple reasons, for example high intravesical voiding pressures, difficult catheterization, repeated symptomatic urinary tract infections or per patient request to discontinue clean intermittent catheterization. Of 7 patients who were catheterized by others 4 elected to discontinue long-term clean intermittent catheterization after an average of 13 months. Overall, 33 patients (66%) discontinued clean intermittent catheterization and 17 are still being followed on a long-term basis. Clean intermittent catheterization is a successful long-term option to drain bladders in spinal cord injury patients who can perform catheterization independently. PMID- 8483213 TI - Functional and urodynamic characteristics of an ileal neobladder. AB - We examined the urodynamic characteristics and symptoms of 28 patients who had undergone the Stanford pouch bladder substitution following cystoprostatectomy. Urodynamics were obtained a mean of 18 months (range 6 to 43) after construction of the neobladder. Mean cystometric capacity was 699 cc (range 366 to 1,370). All patients voided by the Valsalva maneuver and achieved good peak flow rates (mean 19 cc per second). Of the patients 23 emptied to near completion with a mean post void residual of 34 cc, while 5 had post-void residuals of greater than 150 cc (mean 630 cc). The neobladders demonstrated good compliance for the storage of urine, with a mean basal pressure of less than 15 cm. water at volumes of less than 500 cc at which most bladders function, and of 22.4 cm. water (range 1 to 72) at 100% capacity. Phasic neobladder contractions were present during filling cystometrography. While the number increased at higher neobladder volumes, the mean length and mean pressure did not. The mean pressure of contractions was less than 40 cm. water at lower and higher volumes. Daytime continence was attained in 26 of 28 patients (93%), while 17 (61%) attained nighttime continence. Of these 17 patients 14 (82%) had to void at least once at night to stay dry. Daytime incontinent patients had decreased neobladder compliance at high volumes compared to daytime continent patients (p < 0.05) but there was no difference in the maximal urethral closure pressure or the pressure of phasic contractions between these 2 groups. No difference was found in any urodynamic parameter between nighttime continent and incontinent patients. Patients with poor emptying ability (defined as a post-void residual of more than 150 cc) had increased neobladder compliance relative to patients with good emptying ability, as well as a statistically significant increased capacity (1,067 cc versus 623 cc). There was no difference in any important urodynamic parameter between patients who had and had not received postoperative chemotherapy. We conclude that a neobladder constructed from detubularized ileum achieves adequate capacity at low pressures with a satisfactory continence rate. Most patients empty the bladder to completion by Valsalva's maneuver. Low compliance at high volumes appears to be a factor in daytime incontinence. PMID- 8483214 TI - Early presentation of tuberous sclerosis as bilateral renal cysts. AB - We report on an infant in whom bilateral renal cysts were the only initial manifestation of tuberous sclerosis. We review the reported cases of infants with this association and emphasize that tuberous sclerosis can present in infancy as bilateral renal cystic disease. The role of the kidney biopsy in providing the correct diagnosis is discussed. PMID- 8483215 TI - Ossifying renal tumor of infancy. AB - Ossifying renal tumor of infancy is a rare but distinctive tumor that presents as a mass in the pelvicaliceal system. It is usually suspected to be a calculus until surgical exploration reveals dense tumor attachment to the renal parenchyma. The histogenesis of this lesion has not been established. We present a case of this unusual neoplasm. A renal sparing procedure was performed on this biologically benign tumor. Followup after 20 months showed no evidence of recurrence. PMID- 8483216 TI - Safety and efficacy of pediatric ureteroscopy for management of calculous disease. AB - Ureteral calculi, although relatively uncommon in children in the United States, have traditionally been managed with open surgical removal. Innovations in managing ureteral stones in the adult population have not readily been used to manage such problems in children due to unknown effects on the ureterovesical junction and to the unavailability of smaller caliber ureteroscopes. We report on the technique and long-term (average 26 months, range 3 to 56) safety following 18 successful ureteroscopic procedures for stone removal in 16 patients 16 months to 15 years old. All children were rendered stone-free. Followup quantitative renal scans and excretory urography showed adequate renal growth. No incidence of vesicoureteral reflux occurred in 9 of the 14 patients (64%) available for followup who underwent postoperative cystograms. These results suggest that judicious use of smaller caliber instruments, improved ancillary equipment and experience in such procedures make ureteroscopy a safe procedure for management of ureteral calculi in children. PMID- 8483217 TI - Rectal duplication as a cause of neonatal bladder outlet obstruction and hydronephrosis. AB - Duplication of the rectum is a rare embryogenic event with only 70 cases reported in the literature. These lesions manifest as bowel obstruction, hemorrhage, fistula formation, pain or palpable mass. We report a case of bladder outlet obstruction with severe bilateral hydronephrosis caused by rectal duplication. PMID- 8483218 TI - Toilet habits and continence in children: an opportunity sampling in search of normal parameters. AB - An opportunity sampling of 1,192 children regarding parameters of toilet training and elimination status was obtained by interview and questionnaire. Toilet training ages ranged from 0.75 to 5 years, with a mean of 2.4 +/- 0.6 years (standard deviation). Voiding frequency was inversely related to age; most children between 3 and 12 years old urinated 5 to 6 times per day. Influences of gender, urinary infections and parental recall were investigated. Nocturnal and diurnal enuresis was reported in 18% and 10% of our sample, respectively. Bowel movements per week ranged from 1 to 21, with a mean of 6.8 +/- 2.5. PMID- 8483219 TI - Appendicovesicostomy: a useful adjunct to continent reconstruction of the bladder. AB - Appendicovesicostomy is a useful adjunct to continent reconstruction of the bladder. During the last 3 years we have used this procedure in 14 children with difficult incontinence due to spina bifida (7), exstrophy/epispadias (5), imperforate anus (1) and urethral agenesis (1). In 4 patients in whom previous operations had failed to achieve continence the bladder neck was closed. In the remaining 10 children, all of whom had difficulty or discomfort catheterizing the native urethra, the bladder neck/urethra was preserved or reconstructed to serve as a vent for elevated bladder pressures. Continence was achieved in all 14 children with no complications related to the appendix. All children in whom the bladder neck/urethra was salvaged preferentially empty via the appendix and remain dry, except when the bladder is overly full. PMID- 8483220 TI - Augmentation ureterocystoplasty. AB - Augmentation cystoplasy using the gastrointestinal tract has disadvantages related to the intestinal resection and its incorporation into the urinary tract. To preclude both sets of complications, we performed augmentation ureterocystoplasty in a 5 1/2-year-old meningomyelocele patient with urinary incontinence, a low capacity bladder, severe vesicoureteral reflux and a poorly functioning kidney. After nephrectomy the ureter was incised longitudinally, folded over and placed onto the bladder as a patch. Bladder capacity, only 60 cc without the contribution from the refluxing upper tract, increased to 200 cc 6 months postoperatively. The patient is continent. Augmentation ureterocystoplasty is an option for bladder enlargement that obviates many of the risks associated with enterocystoplasty. PMID- 8483221 TI - The effect of gastric augmentation on bladder function. AB - Gastrocystoplasty was performed in 29 female and 14 male patients 1 to 23 years old (average age 11 years). Urodynamic studies were completed in 20 patients preoperatively and within 6 months postoperatively. When postoperative studies were compared with the preoperative evaluation, it was noted that overall capacity increased an average of 220% (range 20 to 750%). Compliance also improved dramatically postoperatively. Bladder pressures increased from a mean volume of 34% of capacity preoperatively to 73% of the post-augment capacity. The average maximum filling pressure decreased by 32%, from 57 to 39 cm. water. Uninhibited contractions resolved completely in 6 of 10 patients who had them preoperatively. No one had uninhibited contractions postoperatively. Cyclical contractions of the stomach segment not exceeding 50 cm. water developed in 6 patients. The gastric patch seems to be an adequate source for improving the dynamics of a poorly functioning detrusor muscle in most patients. When a diamond shaped patch of stomach is harvested and added to the bladder a spherical configuration is created, enhancing the storage properties. This result is in sharp contrast to other bowel segments, which must be detubularized to produce a suitable reservoir. The long-term effects of gastric augmentation remain to be determined. PMID- 8483222 TI - Continence in the myelodysplastic patient following enterocystoplasty. AB - To evaluate the ability of augmentation cystoplasty alone to provide a low pressure bladder and an adequate degree of continence in the myelodysplastic patient, the clinical records and urodynamic data of the last 18 consecutive such patients undergoing augmentation cytoplasty at our institution were reviewed. Two patients underwent colocystoplasty and 16 underwent ileocystoplasty. No patient underwent any procedure on the bladder neck or urethra. The 2 colocystoplasty patients exhibited episodic dampness attributed to contractions of the augmentation but all of the ileocystoplasty patients were dry during the day except 1 who had a urethral resistance of only 19 to 22 cm. water. On the basis of this review, ileocystoplasty alone appears to be sufficient for satisfactory continence in patients with a neurogenic bladder undergoing vesical augmentation if bladder outlet resistance exceeds 25 to 30 cm. water. PMID- 8483223 TI - Lower urinary tract reconstruction using stomach and the artificial sphincter. AB - We implanted the artificial urinary sphincter at gastrocystoplasty in 13 male and 5 female patients. The diagnoses were classical bladder exstrophy (8 patients), myelodysplasia (8), cloacal exstrophy (1) and bilateral ectopic ureters (1). Mean patient age was 14.3 years (range 7 to 32.5). Six patients (5 with bladder exstrophy and 1 with clocal exstrophy) had failed bladder neck continence procedures, 3 myelodysplastic patients had failed artificial urinary sphincter placement, and 1 exstrophy patient had failed a Young-Dees bladder neck repair and artificial urinary sphincter placement. The sphincter cuff was placed around the reconstructed bladder neck in these patients, while in the remainder the artificial urinary sphincter was placed around the intact bladder neck. Mean followup was 20.3 months (range 1 to 5). Of the patients 16 (88%) are continent day and night, while 2 are wet. A total of 11 patients (61%) use Valsalva's maneuver alone for voiding and the remainder use Valsalva's maneuver and/or clean intermittent catheterization for bladder evacuation. Complications related to the artificial urinary sphincter were recurrent pump erosion requiring conversion to a Mitrofanoff continent stoma in 1 patient, and mechanical dysfunction requiring pump cuff and reservoir replacement in 3. There were no complications due to infection. Our report demonstrates that the combination of augmentation gastrocystoplasty and an artificial urinary sphincter leads to urinary continence and can allow for spontaneous urination. The rate of infectious complications is not increased when the 2 procedures are combined simultaneously. PMID- 8483224 TI - Complete genitourinary reconstruction in female epispadias. AB - While female epispadias is a rare congenital anomaly, the treatment of complete epispadias in the female patient does not significantly differ from that of their male counterparts, although the female defect can be overlooked as a cause of incontinence. Attention must be given to the creation of an adequate urethral channel so that an adequate bladder capacity can be achieved and eventual bladder neck plasty can be performed. Finally, attention must be given to the reconstruction of the external genital defect. During the last 7 years 11 female patients with complete epispadias were treated. Of these patients 4 were referred from elsewhere and 3 had failed a previous procedure (2 had recently undergone external genital and urethral reconstruction, 1 underwent urinary diversion after multiple failed bladder neck procedures). Nine patients underwent bladder neck plasty: 5 are completely continent day and night, 3 are dry for greater than 3 hours during the day, and 1 is dry for only 1 to 3 hours during the day and wet at night, for an overall continence rate of 87.5%. Our experience with these patients has taught us that the bladder in this condition is much like that found in complete male epispadias. Therefore, creating a urethral outlet with sufficient length and resistance along with simultaneous reconstruction of the external genitalia allows for bladder regrowth, thus, facilitating achievement of greater volumes and bladder neck reconstruction with an excellent chance of success. PMID- 8483225 TI - Angiocentric myofibroblastic tumor of the penis in a child: case report and literature review. AB - A 6 1/2-year-old boy presented with a painless, white pearly nodule on the glans penis. Wedge excision was performed and pathological examination revealed a benign-appearing, well demarcated nodule confined to the corpus spongiosum. Histological examination revealed a peculiar multinodular myofibroblastic proliferation centered around the vessels within the penis. He has done well for 9 months without evidence of recurrence. To our knowledge this is a previously undescribed lesion arising from the male genitalia. PMID- 8483226 TI - Genitourinary malformations associated with agenesis of the corpus callosum. AB - Agenesis of the corpus callosum is an infrequent congenital anomaly that occurs in partial or complete forms, and is frequently associated with other craniofacial and skeletal abnormalities. An increased association with genitourinary abnormalities has not been previously defined. We reviewed the records of 22 boys and 11 girls with agenesis of the corpus callosum. Of the patients 18 had complete radiological or necroscopic evaluation and 15 had physical examinations as the sole means of evaluation. Renal anomalies were the most frequent genitourinary abnormalities identified in these children, although ureteral, genital and bladder abnormalities were also encountered. There was an exceptionally high incidence of undescended testes (23%), approximately 20-fold greater than the frequency in the normal population, possibly resulting from hypothalamic insufficiency associated with midline cranial defects. We suggest, therefore, that all patients with agenesis of the corpus callosum should be thoroughly evaluated with bladder and renal ultrasound studies to rule out any genitourinary abnormalities. Male patients with agenesis of the corpus callosum and undescended testes should undergo hypothalamic/pituitary axis testing. PMID- 8483227 TI - Renal capsular hemangioma. AB - We present a rare example of hemangioma of the renal capsule. This benign mesenchymal tumor can present diagnostic difficulties, since it can radiographically and macroscopically simulate more common tumors of the kidney, including renal cell carcinoma. If the diagnosis is made or suspected preoperatively or during surgery a more conservative surgical approach should be considered. PMID- 8483228 TI - Unilateral single vaginal ectopic ureter with ipsilateral hypoplastic pelvic kidney and bicornuate uterus. AB - We report on 2 patients with a unilateral vaginal ectopic ureter associated with a single system, ipsilateral hypoplastic pelvic kidney and bicornuate uterus. Although there are many reports of concomitant urinary and reproductive system malformations, a review of the literature shows these unique associations in the same patient to be extremely rare. These findings provide further evidence of the intricate interaction between mesonephric (wolffian) and paramesonephric (mullerian) ducts in the development of the urogenital system. Embryological aspects as well as clinical presentation, diagnostic approach and treatment applicable to this group are discussed. PMID- 8483229 TI - Uretero-fallopian tube fistula secondary to laparoscopic fulguration of pelvic endometriosis. AB - Ureteral injuries during laparoscopic surgery have been documented. We present a case of the diagnosis and management of a uretero-fallopian tube fistula after laparoscopic laser fulguration of pelvic endometriosis. PMID- 8483230 TI - Endoscopic management of incidental cystotomy during operative laparoscopy. AB - Operative laparoscopy is rapidly becoming an important technique used by all surgical specialties. More sophisticated and difficult procedures are continually being performed endoscopically. Complications from these procedures are inevitable and are more frequently being managed with the laparoscope. We describe a case of inadvertent cystotomy during a laparoscopic gynecological operation, which was subsequently repaired endoscopically. The technique and patient followup are presented. PMID- 8483231 TI - Delayed rupture of type I posterior urethral injury: case report. AB - Type I posterior urethral injuries are a frequently noted but infrequently reported entity in the setting of pelvic fracture. Almost all of these injuries will do well with Foley catheter drainage. However, the urethral integrity as established by admission retrograde urethrography is not an unalterable state and serious septic sequelae may be noted if the evolving injury is unrecognized. We report a case of delayed rupture of a type I posterior urethral injury causing infection of the pelvic hematoma and subsequent sepsis. PMID- 8483232 TI - Congenital abnormality of corpora cavernosa and erectile dysfunction: a case report. AB - We report on a young man who had absence of the septum and muscle in the corpora cavernosa. He had no tumescence or erection with either the nocturnal penile tumescence test or intracorporeal injection of a combination of vasoactive drugs. No other urological or extra-urological congenital defects were found. A malleable penile prosthesis was implanted. PMID- 8483233 TI - Necrotizing cavernositis secondary to periodontal abscess. AB - Spontaneous cavernositis is a distinctly uncommon entity. Corporeal infection and abscess formation have been described in association with priapism, cavernosography, intracavernous injection therapy, trauma and penile prostheses. We report a case of acute necrotizing cavernositis in a diabetic patient, which presumably originated with hematogenous seeding from a periodontal abscess. Isolation of typical oral pathogens from corporeal cultures provides bacteriological evidence of a dental source for the corporeal infection. PMID- 8483234 TI - Congenital prostatic cyst causing ejaculatory duct obstruction: management by transrectal cyst aspiration. AB - Congenital prostatic cysts are relatively uncommon and rarely symptomatic. We describe a 24-year-old man who presented with a 2-month history of anejaculation accompanied with bilateral epididymal pain. Transrectal ultrasonography of the prostate revealed a large midline prostatic cyst and bilateral dilatation of the seminal vesicles. Transrectal aspiration of the cyst resulted in return of antegrade ejaculation and resolution of epididymal pain. PMID- 8483235 TI - Electroencephalographic changes from hyponatremia during transurethral resection of the prostate. AB - A patient undergoing transurethral resection of the prostate suffered hyponatremia during the perioperative period. Electroencephalography demonstrated diffuse slowing although the patient was not clinically encephalopathic. The serum sodium level may indicate a trend toward development of the transurethral resection syndrome but the sodium level does not necessarily parallel metabolic changes in brain tissue. Consequently, electroencephalography may aid in the early diagnosis and treatment of encephalopathy during the early phases of the transurethral resection syndrome. PMID- 8483236 TI - Re: Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis. PMID- 8483237 TI - Re: Acquired cystic disease of the kidney: a management dilemma. PMID- 8483238 TI - Re: Renal transplantation in children with posterior urethral valves. PMID- 8483239 TI - Re: Use of methylene blue and selective embolization of the pudendal artery for high flow priapism refractory to medical and surgical treatments. PMID- 8483240 TI - Re: Psoas abscess: case report and review of the literature. PMID- 8483241 TI - Implantable penile venous compression device: initial experience in the chronic canine model. AB - A prosthetic penile venous compression device was surgically placed in 14 dogs to assess the effects of chronic device implantation and repeated device cycling on cavernous tissue. Duration of device implantation ranged from 37 to 224 days; total number of device cycles ranged from 8 to 59. At recovery, erection was induced by electrostimulation of the pelvic nerve. The device successfully prolonged intracavernous elevation for as much as 30 minutes after inflation. Histologic examination of representative tissue sections through the corpora revealed no evidence of neural injury, vascular compromise, or tissue atrophy. The implantable venous compression device may offer an improved method of treatment of venogenic impotence. PMID- 8483242 TI - Inhibitory effect of cromakalim in human detrusor muscle is mediated by glibenclamide-sensitive potassium channels. AB - The effects of cromakalim, a potassium channel activating drug, and glibenclamide, a relatively selective antagonist of ATP-sensitive potassium channels, have been investigated on isolated detrusor muscle from human bladder. Specimens of human bladder were cut into strips and suspended in an organ bath filled with modified Tyrode solution for measurement of isometric contractile force. Concentration-response curves to acetylcholine were constructed before and after pretreatment with cromakalim and cromakalim plus glibenclamide. The concentration-response curves to acetylcholine were displaced to the right, and the maximal response to acetylcholine was significantly inhibited by cromakalim in a concentration-dependent manner. The inhibitory effect of cromakalim on acetylcholine-induced contraction was significantly reduced by glibenclamide. Following sustained contraction induced by 20 mM. KCl, the cumulative addition of cromakalim to the organ bath produced a concentration-dependent relaxation. However, in strips precontracted with 60 mM. KCl, the addition of cromakalim in concentrations as high as 10(-5) M. did not induce relaxation. The relaxation induced by cromakalim in strips precontracted with 20 mM. KCl was significantly inhibited by glibenclamide. These results suggest that the inhibitory effect of cromakalim in human bladder involves activation of glibenclamide-sensitive potassium channels. PMID- 8483243 TI - Fluoroscopically guided incision of ureteral strictures in pigs with the cautery wire balloon catheter: a phase 1 study. AB - We investigated a catheter that can longitudinally incise ureteral strictures under fluoroscopic guidance without the need for ureteroscopy and its attendant risks. The catheter consists of a low-pressure balloon and an overlying cautery wire; the balloon allows precise localization of the stricture, seen as a waist in the balloon, and the overlying cautery wire can be fluoroscopically oriented at the stricture. One to two centimeter ureteral strictures were created in 6 swine. Two to four weeks later strictures were incised in a retrograde or antegrade fashion with the cautery-wire balloon catheter, and double J stents placed for a duration of three weeks. In 5 of 6 renal units strictures improved anatomically with resolution of hydronephrosis at 3 to 4 months' follow-up. Urodynamic absence of obstruction was verified by Whitaker testing. In one animal, the tip of the catheter dislodged in the ureter with subsequent loss of the renal unit. The engineering error that lead to this complication has since been rectified. With correction of the aforementioned problem, this Phase 1 study has demonstrated the feasibility, safety and preliminary efficacy of the cautery wire balloon catheter for endourologic management of ureteral strictures. PMID- 8483244 TI - Rabbit and human renotropin are not epidermal growth factor. AB - Sera obtained from rabbits and humans after unilateral nephrectomy (uni sera) compared with sera obtained preoperatively (control sera) significantly stimulate 3H-thymidine incorporation into the DNA of cultured renal tissue from the respective species. In contrast, rabbit liver cells in culture are not stimulated by the uni sera compared with control sera obtained from rabbits. Mouse epidermal growth factor (EGF) added to tissue cultures significantly stimulates both kidney and liver cells of rabbits and kidney cells of humans. Antiserum against EGF overcomes, at least to some extent, the enhancing effect of EGF under all circumstances, but does not influence the stimulatory ability of uni serum obtained from rabbit and human kidney cells from the respective species. In addition, the activity of EGF was not different in the presence of uni and control sera. This study corroborates the presence of renotropic activity in the sera of rabbits and humans after removal of functioning renal mass and shows that this activity is not derived from EGF, nor does it work by potentiating some aspect of the EGF system. PMID- 8483245 TI - Dynamic enhanced magnetic resonance imaging of testicular perfusion in the rat. AB - Magnetic Resonance Imaging (MRI) has several theoretical advantages in the evaluation of spermatic cord torsion and testicular ischemia. The technique uses no ionizing radiation, has both excellent spatial and temporal resolution and, when used with an intravenous bolus of a paramagnetic contrast agent, provides a semiquantitative assessment of tissue perfusion and vascular injury. In clinical instances of testicular torsion, accurate estimates of tissue perfusion are desirable since testicular salvage is inversely related to the duration of torsion and the degree of tissue ischemia. Perfusion imaging of the rat testis was used as a model to demonstrate the potential use of MRI in the experimental and clinical analysis of disorders that affect blood flow to the testis. PMID- 8483247 TI - Current management of invasive and metastatic transitional cell carcinoma of the bladder. PMID- 8483246 TI - Sensitivity of human renal cell carcinoma lines to TNF, adriamycin, and combination: role of TNF mRNA induction in overcoming resistance. AB - We have examined 6 human renal cell carcinoma (RCC) cell lines for their sensitivity and resistance to the cytolytic effect of tumor necrosis factor (TNF) and adriamycin (ADR), alone or in combination. The results of cytotoxicity mediated by TNF and ADR showed no direct correlation as TNF resistant lines were sensitive to ADR while the TNF sensitive lines were resistant. The combination of TNF and ADR resulted in enhanced cytotoxicity against the tumor lines. Induction of TNF mRNA and protein has been suggested as a mechanism of resistance to TNF in certain tumors. Resistant and sensitive lines were capable of upregulating TNF mRNA after treatment with TNF or PMA+ionophore for periods as short as 1 hour, but only the resistant lines were able to secrete detectable levels of TNF protein. Therefore, a positive correlation existed between resistance to TNF and production and secretion of TNF by the cell lines. In the presence of the protein synthesis inhibitor cycloheximide (CHX), the TNF mRNA level in the TNF resistant lines was increased while the sensitive lines required an additional signal, such as exogenous TNF, to upregulate the mRNA. Due to the enhanced cytotoxicity seen with the combination of TNF and ADR, we determined the effect of this combination on the levels of TNF mRNA. As examined in a constitutively TNF expressing line, ADR alone reduced the constitutive mRNA level and, in combination with TNF, reduced the level of induction produced by TNF. This downregulation of TNF mRNA by ADR may play a role in the enhanced cytotoxicity seen with combined TNF and ADR treatment. The present study demonstrates that RCC cell lines differ in their sensitivity and/or resistance to TNF. Further, ADR and/or TNF resistant RCC lines can be rendered sensitive by combining TNF and ADR. The constitutive and/or inductive secretion of TNF by certain lines and its relationship to tumor pathogenesis as well as overcoming resistance are discussed. PMID- 8483248 TI - Laparoscopic adrenalectomy: the initial 3 cases. AB - Laparoscopic adrenalectomy was performed on 3 patients with primary aldosteronism. Traction with 2 steel skewers placed subcutaneously over the costal arch was combined with conventional intraperitoneal carbon dioxide gas insufflation. This combination provided a good operative field at 8 mm. Hg insufflation pressure. The laparoscopic approach to the adrenal gland requires neither a large skin and muscle incision nor resection of rib(s), and offers lower morbidity and rapid convalescence. Laparoscopic adrenalectomy is a new minimally invasive operation for the treatment of adrenal adenoma. PMID- 8483249 TI - Renal artery stenosis after renal transplantation: the impact of the hypogastric artery anastomosis. AB - A review of 402 renal allotransplants performed during a 5-year period revealed 25 cases of transplant renal artery stenosis in 377 evaluable patients. To our knowledge this is the first large study of this transplant complication in which all patients received cyclosporine immunotherapy. The incidence of transplant renal artery stenosis was 6.6%. The mean internal from transplantation to onset of transplant renal artery stenosis was 11 months. No significant differences in atherosclerotic risk factors were detected between the groups with and without transplant renal artery stenosis. The incidence of acute allograft rejection was not increased in the stenosis group. There was no difference in the incidence of transplant renal artery stenosis following end-to-end (hypogastric artery) or end to-side (common or external iliac artery) arterial anastomoses. Among patients having end-to-end hypogastric artery anastomoses the incidence of transplant renal artery stenosis was significantly greater (p < 0.01) when endarterectomy was required to render the hypogastric artery suitable for use. Percutaneous transluminal angioplasty was performed in 20 patients and open repair was performed in 18. After percutaneous transluminal angioplasty of hypogastric artery anastomoses, more additional procedures were required and there was a higher allograft loss rate when compared to percutaneous transluminal angioplasty of the external iliac artery. These data suggest that treatment of transplant renal artery stenosis in patients with end-to-end hypogastric artery anastomosis is more difficult and results in a higher morbidity rate than treatment in the external iliac artery group. PMID- 8483250 TI - Treatment of renal transplant ureteral complications by percutaneous techniques. AB - From January 1985 to October 1990, 487 adult renal transplantations were performed at our institution. Of 16 ureteral complications noted 15 were initially managed with percutaneous nephrostomy. Of the 8 complications that occurred during the last 2 years 5 resolved on percutaneous nephrostomy and stenting, or stenting with dilation alone. We conclude that percutaneous nephrostomy is indicated as an initial step in the diagnosis and treatment of urological transplant complications, and that it allows for nonoperative resolution of many of these complications. PMID- 8483251 TI - High pressure versus low pressure electromagnetic extracorporeal lithotripsy. AB - A low pressure and an upgraded high pressure electromagnetic lithotriptor were compared for the treatment of calculi within the ureter. The upgrading allows for increased energy density onto the stone surface. We targeted 139 ureteral calculi (average diameter 8.1 mm.) with the low pressure system. The mean number of shock waves was 7,308, 9,226 and 5,304 for calculi in the upper, mid and lower ureter, respectively, and the energy density corresponded to 0.222, mJ./mm.2, 0.224 mJ./mm.2 and 0.223 mJ./mm.2, respectively. Immediate fragmentation was achieved in 39 of 51 upper (77%), 21 of 42 mid (50%) and 22 of 46 lower (49%) ureteral calculi. The upgraded shock wave tube was used in 52 calculi (average diameter 6.1 mm.). The mean number of shock waves was 6,250, 14,150 and 3,400 for calculi in the upper, mid and lower ureter, respectively, and the energy density corresponded to 0.32 mJ./mm.2, 0.33 mJ./mm.2 and 0.30 mJ./mm.2, respectively. Immediate fragmentation was achieved in 11 of 16 upper (69%), 4 of 6 mid (67%) and 7 of 30 lower (23%) ureteral calculi. The comminution rate did not significantly increase, which implies that the focal energy density is not the only decisive parameter in fragmentation by extracorporeal shock wave lithotripsy. PMID- 8483252 TI - Laparoscopic ureterectomy: initial clinical experience. AB - With a combination of cystoscopic and laparoscopic techniques, 3 patients underwent total ureterectomy for urothelial cancer without complication. Of the patients 2 underwent concomitant laparoscopic nephrectomy. Mean operating time was 8.2 hours for the laparoscopic surgery and mean hospital stay was 6 days. In 2 patients the ureter was removed intact, while in 1 it was morcellated along with the kidney before removal. In each case the bladder was closed with a 12 mm. GIA laparoscopic stapling device. After 3 to 9 months of followup no patient had recurrent disease or bladder stones on the staple line. PMID- 8483253 TI - Experience with the hemi-Kock ileocystoplasty with a continent abdominal stoma. AB - We describe our experience with the hemi-Kock ileocystoplasty with a continent abdominal stoma as an alternative to an indwelling catheter or supravesical diversion in 14 women and 4 men with various problems who could not perform intermittent urethral self-catheterization. The aim of management was also to provide, if possible, a competent urethra for additional access. Mean patient age was 37 years (range 22 to 75) and mean followup was 26 months (range 5 to 58). Preoperative management in the 11 wheelchair dependent women with neurological disease was an indwelling catheter in 7, urethral intermittent catheterization with the patient in the supine position in 3 and diapers in 1. Two women with a nonneurogenic bladder and a grossly incompetent urethra (1 after multiple incontinence and fistula repairs, and 1 after severe obstetrical trauma) wore diapers, while 1 with urinary retention and inability to perform self catheterization had an indwelling catheter. The 4 men included 2 wheelchair dependent incontinent spinal cord injury patients who could not be managed with condom drainage, 1 with multiple anomalies who had trouble with self catheterization, and 1 with an impassable postoperative stricture and a suprapubic tube. Surgery included anti-incontinence procedures in 10 patients and bladder neck closure in 3. A total of 15 patients required bladder augmentation in addition to the stoma and 3 had a stoma alone. Postoperative intervention was necessary in 4 women for stomal incontinence and in 2 of these bladder stones were removed simultaneously. One of these women was later treated for recurrent stones cystoscopically through the stoma. Overall, 17 of 18 patients are dry on intermittent stomal catheterization, with 1 lost to followup. We conclude that this procedure is a good alternative in patients with an end stage urethra or who cannot perform urethral catheterization because of physical disability. Establishing urethral continence and maintaining patency leaves a safety valve should the stoma fail. Since the bladder remains as a reservoir no ureteral surgery is necessary. PMID- 8483254 TI - [66th annual meeting of the Japanese Society for Bacteriology. Nagoya, March 24 26, 1993. Abstracts]. PMID- 8483255 TI - [Clinical applications expected in the future--osteoporosis]. AB - Severe vitamin deficiency causes osteomalacia, but osteoporosis is also associated with decreased vitamin D activity. Intestinal calcium absorption is decreased and vitamin D metabolites low in osteoporosis and cytokine and growth factor abnormalities in osteoporosis may be ascribed to vitamin D deficiency. In Japan, 1 alpha (OH) vitamin D3 and 1.25(OH)2 vitamin D3 have been used for osteoporosis with beneficial effect and scarcely any side effects for many years. World wide, the effect of vitamin D on osteoporosis is gradually recognized. The higher the dose, longer the duration of administration and older the age of the patients, more positive effects tend to be obtained. PMID- 8483256 TI - [Renal osteodystrophy]. AB - One of the differences of bone X-ray findings with long-term hemodialysis patients in 1978 and 1991, is a frequency of subperiosteal bone resorption. High incidence of periosteal bone resorption is found in 1978 but in 1991, it is low. In 1978 we did not administer active vitamin D but in 1991 it has already administered for ten years. Administration of active vitamin D is available for the prevalence of periosteal bone resorption but active vitamin D therapy to suppress the secondary hyperparathyroidism occasionally fails in advanced cases and hypercalcemia is found. Intermittent and pharmacologically high levels of plasma calcitriol are reported to suppress the PTH secretion effectively and recently 22-oxacalcitriol, a new active vitamin D analogue, is found to suppress PTH secretion without increasing plasma calcium. It is thought to be a more suitable therapy of secondary hyperparathyroidism. PMID- 8483257 TI - [Fat-soluble vitamin therapy in senile dementia and Parkinson's disease]. AB - In the pathogenesis of Parkinson's disease and senile dementia of the Alzheimer type, free radicals might play a role. Fat-soluble vitamins are a kind of anti oxidative substance. Therefore, fat-soluble vitamins, such as vitamin E, may be useful in treatment of Parkinson's disease and senile dementia of the Alzheimer type. However, it is still unclear whether the concentration of vitamin E in the blood or in the brain tissue, in patients with Parkinson's disease or with of the senile dementia Alzheimer type, is higher than or the same as that in normal subjects. Furthermore, although the effectiveness of vitamin E in the treatment of Parkinson's disease has been reported, the usefulness of vitamin E is still obscure. Further study will be necessary, in order to clarify the role of fat soluble vitamins in the treatment of Parkinson's disease and senile dementia of the Alzheimer type. PMID- 8483258 TI - [Clinical application of fat soluble vitamins to retinopathy of prematurity and intracranial hemorrhage]. AB - More than ten years ago, vitamin E supplementation was proposed as a prophylaxies against a syndrome that might be caused by oxygen toxicity and/or membrane instability such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and periventricular/intraventricular hemorrhage (PVH/IVH). The results obtained from several studies to date does not support the usefulness of vitamin E supplements in the prevention of BPD. However, several reports have suggested the utility of vitamin E in the prevention and/or inhibition of progress of ROP, although the use of vitamin E in premature infants for the possible prevention of severe ROP should still be considered investigational. On the other hand, the aggregate of evidence to date support the efficacy of tocopherol in preventing IVH of extremely premature infants. It is postulated that oxidative damage to capillary endothelial membranes of the subependymal layer predisposed the premature infant to subependymal bleeding and that vitamin E might act as an antioxidant to prevent such damage, thereby reducing the risk of hemorrhage. PMID- 8483259 TI - [The fat soluble vitamins in obstetrics and gynecology]. AB - The therapeutic use of vitamin D in the OB-GYN field is well known for osteoporosis in the climacteric stage, and vitamin K is for the protection of neonatal hemorrhage. The therapeutic use of vitamin E was reviewed, and it was concluded that there was a large number of diseases for example, sterility, toxemia of pregnancy, IUGR, neonatal jaundice, climacteric syndrome, in which a therapeutic value for vitamin E could be clearly establish, vitamin K prophylaxis is also under taken for the neonate. This can be done by giving a dose to the mother just before or in the early stages of labor. Ubiquinone, was given to the man for the treatment of oligospermia. CoQ10 also warrants further investigation for the treatment of fetal arrhythmia in utero. PMID- 8483260 TI - [Structure and function of the scavenger receptor]. AB - The macrophage scavenger receptors are consisted of six domains: cytoplasmic, membrane-spanning, spacer, alpha-helical coiled-coil, collagen-like and a type specific C-terminal. The collagen-like domain is revealed to have important role for ligand binding. The receptor gene is located on human chromosome 8. The human scavenger gene spans approximately 80 kb and is composed of 11 exons. Two types of scavenger receptor mRNA were shown to result from alternative splicing of exon 9 for type II or 10 and 11 for type I to the common exon 1-8. The scavenger receptor proteins were detected in macrophages of various organs and tissues such as Kupffer cells, alveolar macrophages, macrophages in the spleen and lymph nodes and perivascular macrophages in the brain. In the atheromatous plaques, scavenger receptors may participate progression of foam cells. Elimination and detoxication of endotoxin by macrophage scavenger receptor may suggest the defending function against a wide variety of pathogenic agents. PMID- 8483261 TI - [Microwave coagulo-necrotic therapy for hepatocellular carcinoma]. AB - We performed microwave coagulo-necrotic therapy (MCN), a new surgical treatment for hepatocellular carcinoma (HCC) under laparotomy on 41 cases and under laparoscopy on 5 cases for a total of 46 cases (70 cancer nodules). The indications for MCN include: 1) cases in which an early recurrence is judged as likely to occur. For example, multinodular cases, or intrahepatic metastasis (im1 3) 25 cases (54.3%), 9 cases (19.6%) in which multiple adenomatous hyperplasia was detected, VP2 1 case (2.2%). 2) 7 cases (15.2%) in which if hepatectomy is conducted, there is a high risk of postoperative liver failure, or cases in which it is judged postoperative management will be very difficult. In only 4 cases was it because the patients requested laparoscopic MCN (lapa. MCN). Also, the tumor size was less than 15 mm in 4 cases, 16 to 20 mm in 6 cases, 21-30 mm in 21 cases, 31-50 mm in 6 cases, and larger than 51 mm in 9 cases (maximum 90 x 65 mm). Only 1 case who died on the 17th postoperative day due to sudden ventricular arrhythmia, and 3 cases who died cancer death at 1 year 6 months, 2 year 2 months, and 4 years 1 months after the operation for a total of 4 cases, so that 42 patients have survived 4 years and 3 months as of this writing. Thus MCN was in no way inferior to hepatectomy. PMID- 8483262 TI - [The application of confocal laser scanning microscopy (CLSM) in cell biology]. AB - Confocal laser scanning microscopy (CLSM) is expected to provide new optical information different from conventional microscopy in cell biology. CLSM provides high contrast images, individual continuous cellular tomograms without slicing cells, and stereographs which are observed by three dimensional reconstruction. We study the localization of nuclear DNA stained with PI, tumor marker antigen CA 125 stained with FITC, and signals in fluorescence in situ hybridization (FISH) with alpha satellite pericentrometric DNA probe of chromosome 17 to discuss the possibility of its application to cell biology or clinical use. Some of the applications of CLSM including its structure and principle are reviewed. PMID- 8483263 TI - [Fat soluble vitamins]. AB - The first part of this presentation discusses the history of the discovery of vitamins that dates back to the early 20th century. The latter part deals with the basic physical and biochemical functions of fat-soluble vitamins, namely, vitamin A, vitamin D, vitamin E and vitamin K. Unlike water-soluble vitamins, most of which act as a coenzyme binding to an apoenzyme for the formation of holoenzyme, fat soluble vitamins have individual biochemical functions that do not share the same mechanism. Although studies on the mechanism of fat-soluble vitamin function in the cell were hampered due to difficulty in solubilization for in vitro studies in the past, recent progress in the understanding of such mechanisms has been remarkable. PMID- 8483264 TI - [Fat-soluble vitamins: Intestinal absorption]. AB - General principals of drug absorption and bioavailability after the oral administration are discussed in each process of drug release and dissolution from the preparation, such as gastric emptying time and flow of drug in intestinal track, transport through intestinal mucosal microvilli, and the first pass effect of drug elimination in the liver. Character of lipid soluble vitamins in these absorption processes are elucidated with the low solubility in water and solubilization in bile acids micelle. Our studies on dl-alpha-tocopherol solubilization into micelles of bile acids and a detergent and the rat intestinal absorption by perfusion of the micellar solutions are introduced. Faster absorption of the tocopherol solubilized in bile acid micelles, than polysorbate 80, was observed in spite of the less solubilizing abilities of bile acids. Relatively high dependency on volume flow through the intestinal wall was observed in the absorption rate of tocopherol. The dependency is larger in bile acid micelles having smaller size than polysorbate 80 having large size. PMID- 8483265 TI - [Metabolism of fat-soluble vitamins by intestinal flora and enterocytes]. AB - Three topics on fat-soluble vitamins in the intestines are described. First, it was suggested that novel cellular retinol binding protein type II, intrinsic to enterocytes, facilitated not only absorption of retinol and its esterification by lecithin:retinol acyltransferase in enterocytes, but also reduction of retinal to retinol by microsomal retinal reductase. Second, it was shown that in enterocytes the C-24 oxidation pathway from 1,25-(OH)2-D3 to calcitroic acid operated at physiological concentrations and the C-23 oxidation pathway to 1,25-(OH)2-D3-26, 23-lactone was also present as a minor route. Third, it was discussed whether menaquinones produced by intestinal microflora could be utilized by the host animals. Further, antibiotic-associated hypoprothrombinemia was shown to be caused by inhibition of K-epoxide reductase by N-methyletrazole, derived from the antibiotics, rather than reduced population of microflora. PMID- 8483266 TI - [Fat-soluble vitamins: biotransformation]. AB - Fat-soluble vitamins are essential for growth and normal functions of human body. These vitamins are generally absorbed from the gastrointestinal tract only when bile is present. Recently, it is recognized that fat-soluble vitamins have hormone-like functions in the human body. The carotene (provitamin A) is a remarkably potent source of vitamin A, and beta-carotene is the prominent type of carotene in nature. It plays an essential role in the function of the retina. With regard to the biotransformation, more than 90% of the intake of performed vitamin A is in the form of retinol esters, usually as retinyl palmitate. Vitamin A is readily absorbed from the normal gastrointestinal tract, and the absorption of the vitamin is related to that of lipid. Prior to entering the circulation, the hepatic retinyl ester is hydrolyzed and retinol itself is released from the liver. In the blood, vitamin A is present mainly as retinol associated as a protein complex. Normal calcium and phosphate metabolism is dependent on proper levels of vitamin D, and blood levels of these ions are influenced by gastrointestinal absorption, metabolism, and renal excretion of vitamin D. Both vitamin D2 and vitamin D3 are absorbed without esterification from the small intestine. Most of the vitamin appears first in lymph and primarily in the chylomicron fraction as a lipoprotein complex. Bile is essential for adequate intestinal absorption and deoxycholic acid is the most important constituent of bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483267 TI - [Metabolic regulation on retinoic acid and vitamin E function]. AB - 1. Retinoic acid is an oxidative metabolite which is produced intracellularly and plays role in gene expression via nuclear retinoic acid receptor (RAR), a family of steroid receptor. Recently, clinical use of retinoic acid in acute pro myelocytic leukemia (APL) was proposed to induce complete remission in the leukemic cells, which have the t(15:17) of chromosomal anomaly producing a different protein from the normal RAR. From this clinical view, the regulatory role of retinoic acid is becoming clear in the cells. 2. Vitamin E is an antioxidant in biological membranes to prevent from their oxidative chain reaction occurring near the location of vitamin E in the lipid layer of the membranes. Thus, the location of vitamin E, especially alpha-tocopherol differing from the other analogues, in the living body is important to assess its function. From the standpoint of view, absorption of vitamin E from the gut, its circulation in the blood, and transportation to tissues and cells will be discussed in this paper. PMID- 8483268 TI - [Retinoids]. AB - Retinoid includes vitamins A and synthetic relatives except provitamins A such as carotenes. In this review, recent developments on the chemistry and physiological functions of retinoid (retinol, retinal and retinoic acid etc.) were surveyed, special emphasis being laid on the following subjects: (1) vision (retinal and photo-sensitivities; molecular mechanism of scotopic and photopic vision). (2) systemic actions of vitamins A (multiple physiological functions and their active intermediates). (3) reproduction and morphogenesis (extracellular-transport proteins, intracellular-cytoplasmic transfer proteins, and intracellular-nuclear transacting factors; RAR and RXR; morphogen). (4) chemical prevention of cancer (synthetic retinoid derived from retinoic acid). (5) biological significance of cis-retinoid. PMID- 8483269 TI - [Vitamin D]. AB - 1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, stimulates intestinal calcium absorption and osteoclastic bone resorption, resulting in the elevation of plasma calcium. Recent studies have revealed that 1 alpha,25(OH)2D3 also promotes differentiation of various cells such as myeloid leukemia cells, lymphocytes, macrophages and skin keratinocytes. The target cells of 1 alpha,25(OH)2D3 possess 1 alpha,25(OH)2D3 receptors (VDR) which belong to the steroid thyroid retinoic acid receptor gene family. The complex of VDR and 1 alpha,25(OH)2D3 binds to vitamin D3-responsive elements (VDRE) present in the promoter region of target genes of 1 alpha,25(OH)2D3. In bone, osteoblasts possess VDR and synthesize several proteins, such as BGP, osteopontin and the third component of complement (C3), in response to 1 alpha, 25(OH)2D3. 1 alpha, 25(OH)2D3 is involved in the differentiation of osteoclast progenitors into mature osteoclasts directly and also by an indirect mechanism involving some proteins produced by osteoblasts. In this review article, we show the mode of action and the biological function of 1 alpha, 25(OH)2D3. PMID- 8483270 TI - [The biological activity of vitamin E]. AB - The relative biopotency of alpha-(RRR(d)-, 2-ambo (dl)-and all-rac (dl)), beta-, gamma- and delta-tocopherol, tocotrienol homologues and tocopherol derivatives are summarized in the tables. The new United States Pharmacopoeia [USP] XXII NFXVII (1990) does not mention the USP (International) Unit of the six different forms of alpha-tocopherol that has indicated the difference in biopotency between d-alpha-tocopherol and dl-(2- ambo)-alpha-tocopherol and been used for 40 years from 1950. Metabolic and bio-discrimination studies of tocopherols are necessary to determine the precise relative biopotency of d-(RRR)-and dl-(all-rac)-alpha tocopherol. The synergistic effect of all-rac-alpha- tocopherol with its 8 stereoisomers and the biotransformation from beta-, gamma-and delta-to alpha tocopherol are also subjects for further study of the biological activity of tocopherols. PMID- 8483271 TI - [Vitamin K]. AB - Vitamin K has several biological functions in which the major role is a cofactor for gamma-carboxylation of glutamate residues in Gla proteins, such as, several coagulant and anticoagulant proteins for blood clotting. This enzymatic process can be wholly dissolved. If adequate amounts of vitamin K are absent or anticoagulant drugs are administered, this process will be incomplete and abnormal proteins will appear in the blood. Recently, it was found that this carboxylation is blocked by the antibiotics having the N-methyltetrazolethiol group. These antibiotics inhibit vitamin K epoxide reductase, stop the recycling of vitamin K and cause vitamin K deficiency. Vitamin K is also necessary for biosynthesis of osteocalcin, which is a important protein in the normal function of the bone. PMID- 8483272 TI - [Ubiquinones]. AB - Recent topics on the biochemical and clinical aspects of ubiquinone are reviewed in this paper. Dallner and his colleagues have demonstrated that ubiquinone is synthesized, not only in mitochondria, but also on the endoplasmic reticulum Golgi system of the rat liver. New clinical studies that reduction of ubiquinone levels and cardiac functions was induced by treatment with lovastatin, a HMG-CoA reductase inhibitor, have been reported by Folkers et al. According to recent findings, a greater part of ubiquinone in rat and human tissues exists as a reduced hydroquinone form of ubiquinol. On the other hand, good evidence for the antioxidative activity of ubiquinol was obtained from experiments using phosphatidylcholine liposomes and low density lipoprotein. PMID- 8483273 TI - [Determination of retinoids and retinol-binding protein]. AB - The development of high-performance liquid chromatography (HPLC) in the late seventies, enabled us to measure various retinoids in the serum and tissue samples and has contributed to exciting new discoveries of retinoid field. Mainly, serum, retinoids has been measured by reversed phase HPLC with isocratic or gradient mobile eluent. In this paper, several HPLC methods for determining serum retinoids are reviewed. The discovery of plasma retinol-binding protein (RBP) in 1968 has shed new insight into retinoid metabolism. Due to the biochemical character of RBP, serum levels of this protein is a good marker for hepatic reserved function and urine levels for tubular proteinuria. Several methods for RBP determination are also reviewed. PMID- 8483274 TI - [Assay of fat-soluble vitamins--vitamin D]. AB - Methods for determination of vitamin D, 25-OH-D, 24,25(OH)2D and 1,25(OH)2D in plasma are reviewed. A method for simultaneous determination of the D2 and D3 compounds of vitamin D and the metabolites in plasma is established. The method includes extraction of lipid, followed by three steps of HPLC for clean-up and separation. Vitamin D and 25-OH-D are quantified by HPLC with a UV detector, while 24,25(OH)2D and 1,25(OH)2D are assayed by CPBA and RRA methods, respectively. The assayed values for concentrations of the compounds in plasma of normal subjects and various kinds of patients are shown. A simplified method for assaying 1,25(OH)2D in plasma using calf thymus receptor is also introduced. PMID- 8483275 TI - [Measurement of vitamin E from biological samples]. AB - Recent advances in HPLC have enabled to measure small amounts of tocopherols in biological samples. A fluorescence detector is usually used for detection of tocopherols, however we have determined tocopherols of blood samples by an electrochemical detection (ECD). This ECD method is 1,000 times more sensitive than conventional fluorescence methods, and is suitable for detection of small amounts of tocopherols of blood cells. In this report, preparation and extraction methods from blood samples are described. Preparation of blood to separate plasma, platelets, mononuclear cells, and polymorphonuclear cells is performed using a density-gradient method. Extraction of tocopherols usually involves saponification using ethanolic solution of potassium hydroxide. PMID- 8483276 TI - [Vitamin K]. AB - In this paper, highly sensitive methods for measuring of vitamin K in serum, feces and milk are described. Vitamin K1 and the menaquinone family from the serum, feces and milk were separated by high performance liquid chromatography. The separated K1 and menaquinone families were detected by a fluorescence spectrophotometer after their reduction with sodium borohydride or platinum catalyst column. In these methods, minimum detectable quantities of K1, menaquinone-4 and menaquinone-7 were 10, 10 and 50 pg, respectively. More than 95% of supplemented vitamin K1, menaquinone-4 and menaquinone-7 were recovered in the serum and feces. Furthermore, the method of Hirauchi et al. for measurement of vitamin K1 2,3-epoxide in human plasma is introduced. PMID- 8483277 TI - [Determination of ubiquinones in biological material by high performance liquid chromatography]. AB - Quantitative high performance liquid chromatographic (HPLC) methods are described for the determination of reduced, oxidized, and total ubiquinone (UQred, UQox, and total UQ, respectively) in biological material. UQ was extracted into n hexane from an aqueous homogenate after precipitation of protein by addition of alcohol. The n-hexane extract was evaporated to dryness under a N2 atmosphere at 30 degrees C. In order to determine the total UQ, UQred was converted into the corresponding oxidized form (UQox) with ferric chloride. UQox was separated on a reversed-phase column and detected by its ultraviolet absorption (UV275n m). For the simultaneous assay of UQred and UQox, the n-hexane extract was injected onto a HPLC having a UV detector and an electrochemical detector (ECD) coupled in series. UQox was detected by its UV275n m, and UQred by ECD. The HPLC methods described here were applied satisfactorily to the determination of UQred, UQox, and total UQ in human and animal tissues. PMID- 8483278 TI - [Recommended dietary allowances of fat-soluble vitamins]. AB - In Japan the recommended dietary allowances (RDAs) of vitamin A for adult male is calculated at 600 micrograms RE, on the data in a human vitamin A depletion repletion study that minimum requirement for maintenance of a adequate retinol storage at liver is 6.6 micrograms/kg body weight/day. By contrast, it is estimated at 1,000 micrograms RE in U.S., on the basis of a study that minimum requirement for prevention of follicular hyperkeratosis, not impaired dark adaptation, is 910 micrograms RE/day in most adult men. On fourth edition of Japanese RDAs in 1989, the estimated safe and adequate daily dietary intake of vitamin E for adult male was established at 8 mg alpha TE, on the data that the average of unsaturated fatty acid intake was 14.3 g/day and a desirable [vitamin E (mg) to PUFA (g)] ratio of 0.4, whereas the 8-10th editions of U.S. RDAs of vitamin E for adult male had been estimated at 10 mg alpha TE. And the RDAs of other fat-soluble vitamins were discussed on the differences between Japan and other countries. PMID- 8483279 TI - [Vitamin deficiency and marginal vitamin deficiency]. AB - Fat-soluble vitamin deficiency and marginal deficiency of this type of vitamin will be discussed. The trias of vitamin A deficiency is composed of nyctalopia, xerophthalmia and hyperkeratosis follicularis. Vitamin D deficiency causes rachitis and osteomalacia. In Japan, vitamin D deficiency is more often caused by impaired vitamin D activation due to renal failure, than by a lack of sunbathing or insufficient ingestion of vitamin D from diet. At present, it is quite rare that the physician encounters patients with deficiency of vitamin E or other vitamins. According to surveys of occult vitamin deficiency, the prevalence of marginal fat-soluble vitamin deficiency was lower than that of marginal water soluble vitamin deficiency. Marginal vitamin deficiency seems to be absent or very rare among healthy individuals. In patients, however, marginal vitamin deficiency is sometimes observed. Since marginal vitamin deficiency can modify the underlying disease or trigger complications, the physician should take adequate measures to prevent the onset of marginal vitamin deficiency in managing patients with various diseases. PMID- 8483280 TI - [Vitamin A and E deficiency in children, including the marginal deficiency]. AB - 1. Vitamin A: There are very few reports on vitamin A deficiency in Japan because of the rising national status of nutrition, while vitamin A deficiency is still an important nutritional problem in developing and poorly developed countries. In the pediatric field, relationship between vitamin A nutrition and the mechanism for development of bronchopulmonary dysplasia have been discussed, since vitamin A acts as a protector from the keratinization of epithelial cells in the mucosal layer and the skin. The changes in the lung tissues with inadequately supplied vitamin A, probably cause the chronic lung disease resulting from mechanical ventilation in neonates, in whom the plasma vitamin A and retinol binding protein levels are usually low. 2. Vitamin E: In keeping with the view that newborn infants and especially premature infants suffer from vitamin E deficiency. On the basis of recent findings of the vitamin E content in the neonatal cells, the previous concept would agree, as an existing marginal deficiency in neonates. The neurologic deficits manifested in a beta-lipoproteinemia is confirmed to be vitamin deficiency in humans. It has also become clear that similar neurologic impairment occurs in other chronic fat malabsorptive states, such as cholestatic liver diseases, extensive resection of the gut. More recently several patients with spinocerebellar degeneration from vitamin E deficiency without other evidence of malabsorption in whom progression of the diseases is terminated by the vitamin E therapy (isolated vitamin E deficiency) have been reported. The above items are discussed. PMID- 8483281 TI - [Hypervitaminosis D]. AB - Excessive vitamin D causes marked and prolonged hypercalcemia by accelerating intestinal calcium absorption and bone resorption. Vitamin D induced hypercalcemia includes the toxic ingestion of excessive amount of vitamin D preparations, granulomatous diseases and lymphoproliferative malignancies. In vitamin D toxicity, the clinical courses vary depending on the vitamin D preparation responsible for the hypercalcemia. Hypercalcemia state continues for several months when D2 or D3 are responsible for the toxicity whereas the hypercalcemia would subside in a week when 1 alpha(OH) D3 or 1,25 (OH)2D3 are responsible for the toxicity. Abnormal calcium metabolism can be treated by hydration and glucocorticoids. Hypercalcemia is associated with variety kinds of granulomatous diseases, including sarcoidosis and tuberculosis. The granulomatous tissue is believed to be the site of the ectopic production of 1,25(OH)2D3 in which the regulation of the synthesis is quite different from that in the normal kidney. Glucocorticoid markedly diminishes the synthesis. Hypercalcemia associated with elevated serum 1.25(OH)2D3 levels is also found in patients with lymphomas and some other malignancies. However, there still are not sufficient evidences to prove that the excessive amount of endogenous 1.25(OH)2D3 is the primary cause of the hypercalcemia. PMID- 8483282 TI - [Clinical application of vitamin A, D and E against malignant tumor in human]. AB - A great number of epidemiologic studies over the last decade have found that vitamin A, D and E are associated with a reduced risk for malignant tumors in human, though these high levels in blood do not always establish the low risk of a variety of malignant tumors. Consequently, either micronutrient supplementation or/and food fortification are going to be recommended as a prevention strategy of malignant tumors to the general population. On the other hand, concerning the clinical application of these vitamins in the treatment for malignant tumors, most recently, active forms of vitamin A and D are said to be effective in some leukemias. Especially, the administration of all-trans retinoic acid in acute promyelocytic leukemia patients has been established to be more effective and safer than conventional chemotherapies to obtain complete remission. In reviewing these studies, more detailed elucidation in clinical usefulness of these vitamins and as their chemoprevention must await further investigations. PMID- 8483283 TI - [Atherosclerosis, with special reference to vitamin E]. AB - The relationship between atherosclerosis and fat soluble vitamin, especially vitamin E is reviewed on the basis of oxidised modification of low density lipoprotein (LDL). Data now support the notion that the oxidised LDL is present in the blood and arterial wall and antioxidant drugs such as probucol and vitamin E, beta-carotene, may prevent the progression of atherosclerosis. LDL alpha tocopherol levels are generally correlated to the plasma concentrations and supplementation with alpha-tocopherol increases its content in LDL. There is a significant correlation between the LDL alpha-tocopherol level and the resistance to oxidative modification. Epidemiological data also shows the relation between low levels of plasma vitamin E and the increased incidence of coronary heart disease. Clinical application of vitamin E should be clarified in detail to inhibit the progression of atherosclerosis. PMID- 8483284 TI - [Calcium antagonists in the elderly patients]. PMID- 8483285 TI - [Characteristics of clinical asthma types in elderly patients with bronchial asthma]. AB - Asthma was classified into four types, Ia-1 (bronchospasm with 0-49 ml/day of expectoration), Ia-2 (with 5-99 ml/day), Ib (over 100 ml/day) and II (bronchiolar obstruction), according to clinical symptoms. Characteristics of airway responses in each clinical asthma type were compared between 25 elderly (mean age, 65.2 years) and 30 younger subjects (mean age, 44.9 years) with bronchial asthma, by observing ventilatory function and cellular composition in bronchoalveolar lavage (BAL) fluid. 1. In patients with types 1a-2 and Ib, the %V25 value was significantly lower in the elderly subjects than in the younger subjects. 2. Comparing the values of ventilatory parameters of type Ia-1 cases with other asthma types, %V25 value was lower in other asthma types than in type Ia-1 in the elderly. All ventilatory parameters examined were generally lower in type II cases than in other asthma types in the elderly, but this difference was not significant. In contract, in the younger subjects, the values of %MMF, %V50 and %V25 were significantly lower in type II cases than in other asthma types. 3. The proportion of neutrophils in bronchoalveolar lavage (BAL) fluid was higher in the younger patients with type II than in the elderly patients with the same type, although there was no significant difference between older and younger subjects. The proportion of BAL eosinophils in patients with type Ib was significantly higher in younger subjects than in elderly subjects. These results indicate that airway responses which are characteristic of each asthma type are stronger in younger patients than in elderly patients. PMID- 8483286 TI - [Relationship between abdominal fat distribution assessed by computed tomography and serum lipids in the elderly]. AB - A nutritional assessment is necessary to evaluate the pathophysiological state of patients, and serum lipids are one of the factors which must be evaluated. Body fat distribution is considered to be associated with cardiac diseases, metabolic diseases and hypertension. In this study, we performed quantitative measurements of fat distribution by X-ray computed tomography (CT) in 31 elderly outpatients. Thirteen males (mean age 74.8 years) and 18 females (mean age 75.4 years) were examined by abdominal CT. All subjects had body mass indices within the normal range and did not have malignant disease, hyperlipidemia, liver dysfunction or diabetes mellitus. CT scans were carried out at the level of the middle abdomen; these scan slices included intraabdominal fat which consisted of omental, retroperitoneal and perirenal adipose tissues. Subcutaneous fat areas and intraabdominal fat areas were measured from six 10-mm-thick slice films using a 2 dimensional computerized calculator. The relationship between serum lipids and fat distribution was also examined. The ratio of intraabdominal adipose tissue area to subcutaneous adipose tissue area (V/S) was higher in males than in females. V/S correlated positively with serum triacylglycerol and correlated negatively with serum HDL-Ch. These results suggest that the measurement of body fat distribution is important to evaluate lipid metabolism and nutritional states in the elderly. PMID- 8483287 TI - [An elderly case of thrombotic thrombocytopenic purpura]. AB - A 78-year-old woman was admitted to our hospital because of disorientation and fever on January 21, 1992. Two days before admission she experienced vomiting, anorexia and general malaise. Laboratory examinations on admission disclosed a hemoglobin level of 11.1 g/dl and a platelet count of 8,000/microliters. The peripheral blood smear revealed anisocytosis with numerous schistocytes and poikilocytes. Polychromatophilic and nucleated red blood cells were also seen, and the reticulocyte count was 38/1000. Her serum lactate dehydrogenase (LDH) value was 2,977 WU and the total serum bilirubin level was 3.5 mg/dl with 2.7 mg/dl indirect reacting fraction. Serum creatinine was 4.7 mg/dl. Her consciousness became semicomatose after a systemic seizure which lasted approximately 15 seconds and her hemoglobin level decreased to 8.5 g/dl on hospital day 2. Therefore, we diagnosed her as having thrombotic thrombocytopenic purpura (TTP) because of the presence of all 5 features, that is, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic abnormalities, renal dysfunction and fever. A plasmapheresis with fresh frozen plasma (FFP) replacement was begun on that day. She was also treated with anti platelet agents, 80 mg/day aspirin, and 300 mg/day dipyridamole. Moreover, packed red blood cells (PRC) were infused. While also receiving diphenylhydantoin and phenobarbital to prevent convulsions, status epilepticus developed on day 3. Because of inhibited spontaneous respiration which was an adverse effect derived from diazepam and sodium thiamylal administered intravenously to treat the status epilepticus, an artificial respiration was initiated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483288 TI - [A case of primary systemic amyloidosis with skeletal muscle atrophy and congestive heart failure]. AB - A 77-year-old male had been noticing progressive weakness of the legs for three years. By the age of 75 he had difficulty in climbing stairs. On admission, serum level of CPK was moderately high. There were weakness and atrophy of the proximal muscles. Deep tendon reflexes were depressed. Sensation was normal. The electromyogram and the biopsy of the femoral quadriceps muscles showed nonspecific changes. In 1989, he developed difficulty in walking and had congestive heart failure. On the second admission, moist rales were heard over the chest, and pitting edema was present in the lower extremities. The chest roentgenogram showed a cardiothoracic ratio of 63% and bilateral pleural effusion. The electrocardiogram showed atrial flutter with 2:1 conduction, QS in V1-3, rS in V4, and ST depression and T inversion in V5,6. The echocardiogram revealed a thick left ventricular wall and impaired left ventricular contraction (EF 22%). Macroglossia, hepatosplenomegaly and renal dysfunction were not noted. Congestive heart failure progressed and he suddenly died of ventricular tachycardia in December 1989. At autopsy, skeletal muscle fibers varied in size and showed fiber splitting. A cellular infiltration was observed in the stroma. Amyloid deposit was positively stained with Congo red. The heart weight was 570 g with marked left ventricular hypertrophy and moderate bilateral atrial dilatation. In both atria and ventricles, extensive amyloid deposition was found around myocardial fibers as well as in perivascular spaces. Amyloid was present also in the liver, the kidneys, the gastrointestinal tracts, and the other organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483289 TI - [Complete remission of acute promyelocytic leukemia accompanied by DIC in an elderly patient treated with all-trans retinoic acid]. AB - In this paper we report on a 74-year-old female patient who was suffering from acute promyelocytic leukemia (APL) and who, upon admission to our hospital on February 20, 1992, was also found to be stricken with disseminated intravascular coagulation (DIC). The DIC, however, was quickly arrested by administration of heparin and there was no exacerbation. Also, on admission her peripheral blood leukocyte count was 700/ul, but after oral administration of all-trans retinoic acid (ATRA) (45 mg/m/day) was begun on February 22, this count gradually increased and peaked at 35,200/ul on March 7. Some of these matured leukocytes revealed dysplastic features; some had Auer bodies. At this time cytogenetic analysis of bone marrow cells showed 46XX, t (15;17). The leukocyte count gradually decreased to 1,500/ul, and the dysplastic features disappeared. On March 21 her thrombocytes and reticulocytes began to increase, and she achieved complete remission when her abnormal karyotype disappeared on March 24. She suffered no severe complications such as infection or hemorrhage during treatment. We therefore suggest that ATRA is very effective for APL in elderly patients. It neither exacerbates DIC nor increases the risk of infection. In fact, when ATRA treatment is compared to the standard cytotoxic chemotherapy there is a reduced risk of infection. PMID- 8483290 TI - [Aging and serum protein]. PMID- 8483291 TI - [77th Congress of the Medico-Legal Society of Japan. April 21-23, 1993/Fukuoka. Abstracts]. PMID- 8483292 TI - Effects of BMY-21502 on anoxia in mice. AB - The protective effects of BMY-21502 (1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4 piperidinyl]methyl]-2- pyrrolidinone) against cerebral anoxia were investigated using various models in mice, in comparison with those of other cerebroactive drugs. Oral administration of BMY-21502 (10-100 mg/kg) significantly prolonged the survival time in KCN (2.4 mg/kg, i.v.)-induced anoxia. Oxiracetam and idebenone exerted similar but weak protection at doses above 100 mg/kg, p.o. and only at a dose of 100 mg/kg, p.o., respectively. Significant protection by BMY 21502 against moderate hypobaric hypoxia was observed at doses of 30 and 100 mg/kg, p.o. Idebenone (100 and 300 mg/kg, p.o.) significantly prolonged the survival time of mice in this model, but oxiracetam (30-300 mg/kg, p.o.) did not. Oral administration of all of these drugs (BMY-21502, 3-300 mg/kg; Oxiracetam, 100-1000 mg/kg; Idebenone, 100-1000 mg/kg) failed to increase the number of gasps and the duration of gasping in the decapitated head of mice as a complete ischemic model. The anti-anoxic effect of BMY-21502 in the KCN-anoxia model was blocked by pretreatment with scopolamine. These findings suggest that BMY-21502 has an anti-anoxic action superior to those of the other cerebroactive drugs used, and activation of the CNS cholinergic system is involved as one of the causative mechanisms for the anti-anoxic effect of BMY-21502. PMID- 8483293 TI - Leakage of the fluorescent Ca2+ indicator fura-2 in smooth muscle. AB - The movement of a fluorescent intracellular Ca2+ indicator, fura-2, in smooth muscle was examined. Strips of rat and rabbit aortas and bovine trachea were loaded with the acetoxymethyl ester of fura-2 (fura-2/AM), followed by washing with normal physiological solution. Not only fura-2/AM but also fura-2 was detected in the washout solution. The amount of fura-2 in the cells, measured fluorometrically, decreased gradually during the washout. The decrease was fastest in rat aorta followed by rabbit aorta > bovine trachea. In rat aorta, fura-2 leakage was inhibited by an inhibitor of anion transport, probenecid, or by a decrease in bath temperature. The Ca2+ ionophore ionomycin (10 microM) increased the leakage of fura-2, which was not inhibited by probenecid, possibly because a high concentration of ionomycin nonselectively increased membrane permeability. These results suggest that fura-2/AM is cleaved to fura-2 in the cell which gradually leaked out of the cell mainly by an anion transport system. The amount of fura-2 in the cell seemed to be determined mainly by the rate of leakage of fura-2, which is the largest in rat aorta followed by rabbit aorta and bovine trachea. PMID- 8483294 TI - Calcium-induced vasodilation due to increase in nitric oxide formation in the vascular bed of rabbit ear preparation. AB - Participation of calcium-induced vasodilation (due to an increase in synthesized nitric oxide (NO) content in endothelial cells) in the arterio-venous circulation, including the vascular bed was investigated by the vessel perfusion method in the isolated rabbit ear preparation. The perfusion medium used was a tris-buffered solution. When CaCl2 (6.25, 12.5 and 25 mg) was injected in the perfused vessel of the rabbit ear preparation, dose-dependent vasocontraction was observed when vascular tone was kept at a normal level. However, CaCl2 dose dependently induced vasodilation of the vessel when it was continuously contracted by norepinephrine (1.2 x 10(-7) M). This calcium-induced vasodilation was inhibited in the presence of NG-nitro-L-arginine (5 x 10(-5) M), a selective inhibitor of NO synthesis, and methylene blue, a guanylate cyclase inhibitor, although it was rarely affected by indomethacin (10(-5) M), a cyclooxygenase inhibitor. Calcium-induced vasodilation was also obtained in the in situ circulation containing vascular bed, and this suggests that the vasodilation was due to a Ca(2+)-induced increase in the synthesis of NO derived from endothelial cells. PMID- 8483295 TI - Mechanisms of the inhibitory action of semotiadil fumarate, a novel Ca antagonist, on the voltage-dependent Ca current in smooth muscle cells of the rabbit portal vein. AB - Effects of semotiadil on the voltage-dependent Ca current (ICa) were investigated in dispersed smooth muscle cells of the rabbit portal vein. At a holding potential of -100 mV, semotiadil (> or = 0.1 microM; dissolved in dimethylsulphoxide, DMSO) inhibited the ICa in a concentration-dependent manner (IC50 = 2.0 microM, Hill's coefficient = 1.0). At a holding potential of -80 mV or -60 mV, the concentration-inhibition curve observed in the presence of semotiadil was shifted to the left compared with that observed at -100 mV; and semotiadil shifted the voltage-dependent inactivation curve to the left. The curve for the decay of ICa was fitted with two time constants. Semotiadil (< 1 microM) reduced the slow but not the fast time constant. The curve for the recovery from ICa inactivation also consisted of two time constants, and semotiadil (1 microM) prolonged the slow recovery. Semotiadil dissolved in deionized water more potently inhibited ICa than semotiadil dissolved in DMSO. At pH 10.0, semotiadil did not modify the voltage-dependent inactivation curve. However, recovery from the inactivation was much faster at pH 10.0 than at pH 7.3. These results indicate that the voltage-dependent inhibition of ICa by semotiadil may be due to binding of the ionized drug during the inactivated state and also inhibition of the transition from the inactivated to the resting state. Long-lasting inhibition of ICa after removal of semotiadil may be due to tight binding of semotiadil on the channel through a hydrophobic site. PMID- 8483296 TI - Circadian rhythm in the cerebral resistance to hypoxia in mice. AB - The cerebral resistance to hypoxia in mice was investigated by measuring the survival time under both hypobaric and normobaric hypoxic conditions. In the ad libitum fed mice, there was a circadian variation in the survival time that was longer during the light period than during the dark period under hypobaric hypoxic conditions. The survival time under normobaric hypoxic conditions also exhibited a similar circadian variation in the ad libitum fed mice, whereas the rhythm of the survival time was completely reversed by the restriction of food presentation (9:00-15:00). These findings suggest that there is a circadian rhythm in the cerebral resistance of mice to hypoxia, which can be shifted by the time of food presentation. Furthermore, regression analyses revealed a negative correlation between the survival time of mice exposed to hypoxia and body temperature, and blood glucose levels. These indicate that the cerebral resistance to hypoxia was intimately associated with body temperature and blood glucose that both show a circadian rhythm in mice. PMID- 8483297 TI - Regulation of spontaneous acetylcholine release in the hypothalamic vasopressinergic supraoptic nucleus of a freely moving rat: a study by in vivo microdialysis. AB - We employed a brain microdialysis method to examine the possible regulation of spontaneous acetylcholine (ACh) release in the hypothalamic vasopressinergic supraoptic nucleus (SON) of rats. We monitored the basal ACh release in the SON microdialysate. The addition of tetrodotoxin (10(-6) M) to the perfusate (saline containing 10(-4) M physostigmine) decreased the basal ACh release. A muscarinic receptor antagonist, atropine (non-selective) or pirenzepine (M1-selective), increased the basal ACh release in a concentration-dependent manner. The maximal increase occurred at 20-40 min after the start of the infusion of antagonists. The ED50 values for the stimulatory effects of atropine and pirenzepine were 9.4 x 10(-8) and approx. 10(-4) M, respectively. The effect of atropine (10(-6) M) was inhibited by simultaneous addition of the muscarinic agonist oxotremorine (10(-5) M). The results showed a negative feedback regulation of the spontaneous ACh release through the activation of muscarinic receptors in the SON. The weak effect of pirenzepine in increasing the ACh release, compared with atropine, suggests that ACh release in the nucleus is mainly regulated by the non-M1 muscarinic receptor subtype. PMID- 8483298 TI - Novel low immunosuppressive derivatives of the antitumor drug fluoropyrimidine, UK-21 and UK-25: effect on delayed type hypersensitivity and tumor immunity. AB - Previously, we reported that two novel 5-fluoropyrimidine derivatives, 2',3',5' tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21) and 1-(6-[N-(2 n-propyl-n-pentanoyl)glycyl]amino-n-hexylcarbamoyl)- 5-fluorouracil (UK-25), show potent antitumor activity with low immunotoxicological effects. The purpose of this paper was to evaluate the effect of these drugs on delayed type hypersensitivity (DTH). Not only UK-21 and UK-25 but also tegafur (FT-207) and 5 fluorouracil (5-FU) produced no suppression of picryl chloride (PC)-induced DTH in mice but rather enhanced it. It is known that variation of the sensitizing antigen dose alters the effect of drugs on the immune response. Because it was difficult to control the antigen dose in PC-DTH, the sheep erythrocyte (SRBC) induced response was used to examine the effect of drugs on delayed type hypersensitivity in the succeeding experiments. Either a therapeutic dose or an over-dose of the respective drug was given to mice sensitized with 5 x 10(5) or 5 x 10(7) SRBC. The suppressive effects of UK-21 and UK-25 on the DTH were lower than those of FT-207 and 5-FU. UK-21 and UK-25 enhanced Meth A tumor-specific DTH in BALB/c mice, but FT-207 and 5-FU did not. UK-21, UK-25 and FT-207 showed a tendency to enhance or restore the Meth A tumor neutralizing activity of spleen cells in mice bearing the tumor, but carmofur (HCFU) did not. These results indicated that the suppressive effects of UK-21 and UK-25 on the tumor immune response were also low. PMID- 8483299 TI - Characterization of a novel aldose reductase inhibitor, TAT, and its effects on streptozotocin-induced diabetic neuropathy in rats. AB - TAT ([5-(3-thienyl)tetrazol-1-yl]acetic acid) is a novel aldose reductase (AR) inhibitor. It exhibited highly potent inhibition of partially purified AR from rat lens (IC50 = 2.1 x 10(-8) M), rabbit lens (IC50 = 2.3 x 10(-8) M) and human placenta (IC50 = 2.8 x 10(-8) M). On the other hand, TAT had a weak inhibitory activity against mouse liver aldehyde reductase (ALR) (IC50 = 2.4 x 10(-6) M) and poor inhibitory activity against several adenine nucleotide-requiring enzymes. Against rat lens AR, TAT exhibited an uncompetitive inhibition at a concentration of 1.0 x 10(-8) M and a mixed type inhibition at higher concentrations. TAT inhibited sorbitol accumulation in the isolated rat sciatic nerve (IC50 = 1.0 x 10(-6) M), rat lens (IC50 = 5.7 x 10(-6) M), human erythrocytes (IC50 = 2.5 x 10( 7) M), and rabbit erythrocytes (IC50 = 2.1 x 10(-7) M) incubated with high glucose concentrations. The oral administration of TAT (5-100 mg/kg/day) to streptozotocin (STZ)-induced diabetic rats during a 5-day treatment period decreased the sorbitol content in the sciatic nerve, dose-dependently (ED50: 8.8 mg/kg/day for the prevention and 9.0 mg/kg/day for the reversal). Moreover, TAT (2.5-40 mg/kg/day) improved the decreased motor nerve conduction velocity (MNCV) after a 14-day treatment period. There was a significant correlation between MNCV and sciatic nerve sorbitol content. From these results, TAT is expected to be useful for the clinical treatment of diabetic complications. PMID- 8483300 TI - Comparative effects of cimetidine and famotidine on the vagally stimulated acid secretion in the isolated mouse whole stomach. AB - We investigated the effects of cimetidine and famotidine on the acid secretory response to electrical vagal stimulation, bethanechol and histamine in the isolated mouse whole stomach preparation. The acid secretion elicited by electrical vagal stimulation at the position of the esophagus (10 Hz, 0.3 msec, 10 V for 5 min) was reproducible by repeated stimulation in each preparation, and it was abolished by tetrodotoxin, atropine and hexamethonium. This vagally stimulated acid secretion was abolished by cimetidine (3 mM), while it was only partly inhibited by famotidine (10-100 microM). Histamine (100 microM)-induced acid secretion was inhibited by cimetidine and famotidine, and the doses of these drugs required for complete inhibition were 3 mM and 10 microM, respectively. In contrast, bethanechol (10 microM)-induced acid secretion was slightly reduced by famotidine (1-100 microM), but markedly reduced by cimetidine (3 mM). In the guinea pig ileum, millimolar concentrations of cimetidine and famotidine shifted the dose-response curve of the contractile response to acetylcholine rightward. These findings suggest that the inhibitory effect of cimetidine on the vagally stimulated or bethanechol-induced acid secretion is elicited at least partly through mechanisms different from H2-antagonism. PMID- 8483301 TI - Involvement of serotonergic receptor subtypes in the production of antinociception by psychological stress in mice. AB - Besides the important role of emotional factors in the production of psychological-stress-induced analgesia (PSY-SIA), recent attention to the participation of serotonergic (5-HTnergic) neurons in the fear- and anxiety evoking mechanism led us to examine the effects of 5-HTnergic ligands on PSY-SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT1A receptor partial agonist, dose-dependently suppressed the production of PSY-SIA. Ritanserin, a 5-HT2 receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25,130, a 5-HT3 receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited PSY-SIA dose-dependently, while (+/-)pindolol, a 5-HT1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of PSY-stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25,130, but not by (+/-)pindolol. These results suggest that 5-HT receptor (5-HT1A, 5-HT2 and 5-HT3 but not 5-HT1B)-mediated mechanisms play an important role in the production of PSY-SIA. PMID- 8483302 TI - Renal tubular site of action of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized rats. AB - The mechanism of the diuretic action of KW-3902 (8-(noradamantan-3-yl)-1,3 dipropylxanthine), an adenosine A1-receptor antagonist, was investigated by a lithium clearance study and stop-flow method in anesthetized rats. KW-3902 increased urine volume (UV), sodium excretion and renal clearances of sodium (CNa) and lithium (CLi), when UV and CNa increased more than CLi. KW-3902 did not affect the stop-flow pattern, whereas trichlormethiazide inhibited the reabsorption of water and sodium at the distal nephron. These results suggest that the adenosine A1-receptor blockade exhibits diuretic effects via the inhibition of reabsorption of water and sodium mainly at the proximal tubule. The additional small contribution of the distal action can not be ruled out. PMID- 8483303 TI - Antisecretory and antiulcer effects of ebselen, a seleno-organic compound, in rats. AB - The effects of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-on), a metal containing organic compound, on gastric secretion and gastric ulceration were examined in rats. Intraduodenal ebselen (30 to 300 mg/kg) significantly and dose dependently inhibited gastric secretion in pylorus-ligated rats. Both aspirin- and water-immersion restraint stress-induced ulcers were significantly prevented by oral administration of ebselen at doses equivalent to the antisecretory doses. These results indicate that the antisecretory effect of ebselen underlies its antiulcer effect in these models. PMID- 8483304 TI - [Addictive diseases--more understanding through additional education?]. PMID- 8483305 TI - [Nurses face drug abuse]. PMID- 8483306 TI - [Rape. How can nurses help?]. PMID- 8483307 TI - [Hanne Pelzer, geriatric nurse]. PMID- 8483308 TI - [Attitudes toward HIV positive and AIDS patients. A poll among nurses]. PMID- 8483309 TI - [The role of nursing in the therapeutic team]. PMID- 8483310 TI - Effect of conduction distance on amplitude and area of compound action potentials of A fiber and C fiber. AB - We used 24 sacral dorsal roots of the rat to analyze amplitude and area changes of biphasic and monophasic compound action potentials (CAPs) at 4 conduction distances. Both the CAPs of the A-fiber and C-fiber were analyzed. The changes were examined with the paired t test and linear regression. All the variables decreased linearly with increasing conduction distance except area of monophasic CAP, which remained constant throughout. CAP data were also compared between the S1 and S2 roots by using the pooled t test. Only area of monophasic CAP showed good correspondence with the anatomical data. Therefore, area of monophasic CAP is suggested as the best parameter for representing the functional state of a nerve. PMID- 8483311 TI - Oxygen tension clamp around single neurons in vitro: a computerized method for studies on O2 deprivation. AB - This report presents a novel computerized oxygen tension clamp for use with single neurons. One main objective for developing such a system is to be able to study the intrinsic response of single neurons to graded hypoxia. The device described in this paper is comprised of three major subsystems: (1) an oxygen monitoring subsystem, (2) a motorized perfusion subsystem and (3) a computer subsystem for data acquisition and control. The clamp uses an oxygen scavenger (sodium hydrosulfite) to decrease O2 availability. The system has many advantageous features: (a) studies on hypoxia can be carried out without using chemical metabolic inhibitors to simulate hypoxia; (b) precise control of the O2 level around a given cell is feasible for extended periods of time; (c) rapid and accurate changes in the O2 level around a cell can be made because the O2 level is continuously monitored and adjusted by a computer; (d) other cells outside of the immediate vicinity of the cell being studied are not subjected to hypoxic exposures; and (e) the system is inexpensively built around readily available components. PMID- 8483312 TI - An apparatus for controlled stretch of human jaw-closing muscles. AB - The design of a special-purpose muscle stretcher for reflex studies of the human jaw-closing muscles is described. The device is based on a servo-controlled electromagnetic vibrator which imposes controlled displacements on the lower jaw. The mechanics of the device keep jaw movements coaxial with the temporomandibular joint during the stretches. The design incorporates important safety features including mechanical stops and electronic cut-outs to protect the jaws from excessive stretches. PMID- 8483313 TI - Behavioral evaluating methods in the objective clinical assessment of motor function after experimental brachial plexus reconstruction in the rat. AB - Unfortunately, the results of brachial plexus surgery have not fulfilled expectations. Although the components of the rat brachial plexus are similar to those of the human plexus, experimental work in this field is limited. No functional test to assess experimental brachial plexus reconstruction has so far been published. We worked out a method of evaluating brachial plexus impairment in rats in the laboratory. It consists of a simple test in which a bowl of water is projected over the animal's head, eliciting grooming movements of the forepaws towards the head. This test is therefore called the 'grooming test'. A system of scoring the animals' performance is suggested. Rats were also submitted to walking tracks analysis, but this was of limited value in assessing brachial plexus impairment. PMID- 8483314 TI - A new configuration for voltage clamp of axons used to demonstrate nerve conduction blockade by a 2,5-disubstituted pyrrolidine. AB - An original voltage-clamp technique on axons from crayfish Procambarus clarkii is described in this paper. Its advantages are: a fast dissection leading to the availability of several fibers of different diameters (10-500 microns) that may contain different ion channels; and use of a double-electrode voltage clamp on a chosen fiber with good clamping characteristics (short time clamp and good space clamp, small leak conductance). Because of the absence of exogenous lipidic phase in the superfusion chamber, this technique appears particularly suited to studying how liposoluble neurotoxins affect nerve conduction. This method has been successfully applied to test the effect of a synthetic derivative (2-(1non 8enyl)-5(1non-8enyl)pyrrolidine (Pyr 9)) of ant venom alkaloids from Monomorium species on nerve conduction. We present here evidence of a strong blocking effect on inward current involved in spike conduction. The resting potential of the treated axons did not change and it appears that only the inward current was affected. PMID- 8483315 TI - Algorithm for semi-automatic sorting of objects to specified tissue domains. An aid for co-ordinating morphometric data with identified tissue components. AB - A personal computer-based technique was developed that reduces the extent of human efforts in obtaining data, like numerical density of profiles on area, describing the distribution of specific features of histological sections, e.g., density of synaptic profiles or of histochemical reaction products in specified tissue compartments. The procedure consists of (i) marking the objects to be counted, (ii) recording the borderlines of (reference) tissue domains of interest, and (iii) allocating the marked objects to the corresponding domains automatically. This automatic sorting of objects into defined tissue domains is achieved by an algorithm operating on two sets of coordinates: (i) coordinates of points that constitute the boundary of tissue domains (perimeter points) and (ii) coordinates of points marking the particular objects to be sorted. The principle of the sorting calculation is to construct 'segments' of the loop by lines parallel to the ordinate which pass through neighbouring perimeter points. The 'items' to be sorted are classified by the sign of marker flags allocated to each point depending on which side of the perimeter segment they are located. Segmentation and classification procedures are sequentially repeated along the entire perimeter of each domain specified by the operator which may result during the procedure in multiple changes of the sign of the flags. The internal or external location of each item finally is represented by the last sign of its flag. Objects, allocated to domains can be counted and processed further for numerical density determination. PMID- 8483316 TI - A technique for recording from spinal neurones in awake sheep. AB - A technique is described for implanting a chamber on 1 or 2 vertebrae of the spinal column of the sheep. This chamber protrudes permanently through the dorsal skin of the back and is covered by a light bandage. Between recording sessions the chamber houses an inner cap sealing the hole that gives access to the cord. During recording sessions this cap is removed and a miniature manipulator inserted instead. This manipulator can accept a motor drive that holds a glass coated tungsten microelectrode. The drive has a hole through which an arthroscope tube can be passed so that insertion of the electrode can be performed under visual control. Extracellular recordings have been made of single spinal neurones for up to 4 h in animals that are drug-free, untrained and only lightly restrained. Recording sessions can be repeated on a daily basis for several weeks until the dura and/or arachnoid becomes too thickened to permit electrode penetrations. Animals remain healthy and their behaviour remains normal throughout this time. PMID- 8483317 TI - Metal (Fe3+) affinity chromatography: differential adsorption of tau phosphoproteins. AB - Tau is a neuronal cytoskeletal protein consisting of a group of isoforms with apparent molecular masses ranging from 45 to 62 kDa. Tau purified from brain exists in multiple phosphorylated forms and abnormally phosphorylated tau appears to play an important role in the neuropathology of Alzheimer's disease. To separate the differentially phosphorylated populations of tau, a chromatographic technique using ferric ions adsorbed onto iminodiacetic acid substituted Sepharose was developed. Several distinct populations of tau were isolated based on the phosphorylation state. These preparations can be used for further investigation of how each specific phosphorylation state modulates the metabolism and function of tau. PMID- 8483318 TI - Induction of DNA strand breaks associated with apoptosis during treatment of leukemias. AB - A new flow cytometric method is described to detect DNA strand breaks associated with apoptosis, by labeling the 3'-OH termini in the breaks with biotinylated dUTP in a reaction employing exogenous terminal deoxynucleotidyl transferase. The method has been applied in studies on leukemic HL-60 and MOLT-4 cell lines to reveal whether it is specific to apoptotic cells, and whether it can be used in the clinic to detect DNA breakage in leukemic cells during chemotherapy. There was labeling of mononuclear cells in peripheral blood of all 11 patients studied during chemotherapy for acute lymphoblastic, acute myelogenous, or chronic myelogenous leukemia (ALL, AML, or CML) in blastic crisis, indicating induced DNA damage; the number of labeled cells increased from 1-8% before treatment up to 80% during the course of treatment. The DNA topoisomerase inhibitors mitoxantrone, VP-16 (etoposide), and m-AMSA (amsacrine) were more effective in inducing DNA breaks than was hydroxyurea or cytosine arabinoside (AraC). Cells with DNA breaks were identified in peripheral blood for up to 5 days following administration of Mitoxantrone and VP-16. In the case of DNA aneuploid leukemias, the DNA breaks were predominant in the aneuploid cell subpopulations, whereas presumably non-neoplastic diploid cells were unlabeled. In one case of ALL there were two distinct subpopulations of aneuploid cells: one responded to the treatment (by DNA breakage) and the other was non-responding. Thus, cells undergoing apoptosis can be detected by this method of labeling DNA strand breaks and the technique is applicable for analysis of response of leukemic cells to chemotherapy. With this method it may be possible to identify tumor cell sensitivity or resistance to particular drugs early in the course of treatment. PMID- 8483319 TI - Detection and clinical relevance of genetic abnormalities in pediatric acute lymphoblastic leukemia: a comparison between cytogenetic and polymerase chain reaction analyses. AB - The E2A/PBX1 and the BCR/ABL fusion genes result from the t(1;19)(q23;p13) and the t(9;22)(q34;q11), respectively, and encode oncoproteins which are thought to play an important role in the development of acute lymphoblastic leukemia (ALL) subtypes associated with adverse prognosis. The use of the polymerase chain reaction (PCR) for the detection of these genetic rearrangements may offer advantages over cytogenetic techniques which are often unsatisfactory in patients with ALL and, furthermore, provide a useful tool for monitoring of residual disease. However, it has not yet been evaluated whether the employment of PCR at the time of diagnosis improves the detection rate of these clinically relevant genetic anomalies. We have developed a multiprimer-PCR protocol which facilitates the detection of each of the four chimeric E2A/PBX1 and BCR/ABL mRNAs in a single reaction. This protocol was used for the evaluation of bone-marrow or blood samples from 251 children with ALL in whom cytogenetic analyses had been performed. Of the 251 patients, 221 had a B-cell precursor immunophenotype. In this group, 21 patients (9.5%) carrying the E2A/PBX1 rearrangement and three patients (1.4%) with BCR/ABL transcripts were detected by PCR. Twelve of these cases had escaped the detection by conventional cytogenetic analysis. In two of 12 patients with a typical t(1;19)(q23;p13), no E2A/PBX1 transcripts were identified by PCR, thus suggesting the presence of different molecular rearrangements. Residual leukemic cells were detected by PCR in five of eight patients who were followed during complete clinical remission. The frontline use of PCR has an important impact on the timely diagnosis, therapeutic decisions, and monitoring of high-risk patients with B-cell precursor leukemia who carry the E2A/PBX1 or BCR/ABL fusion genes. PMID- 8483320 TI - Characterization of acute myeloid leukemia (AML) coexpressing lymphoid markers: different biologic features between T-cell antigen positive and B-cell antigen positive AML. AB - The clinical and biologic characteristics of acute myeloid leukemia (AML) with coexpression of lymphoid-associated antigens (Lym+ AML) were studied from 39 cases who represented 24% of 161 newly diagnosed de novo AML. Twenty-seven cases (16.8%) were positive for the expression of T-cell markers (T+ AML) and 12 (7.5%) for B-cell markers (B+ AML). Chromosomal abnormalities t(9;22)(q34;q11) and t/del(11)(q23), which were considered to be associated with acute leukemia coexpressing markers of more than one cell lineage, were detected in five and in four patients, respectively. There was no prognostic significance of B-cell or T cell antigen expression in AML. Of 12 T+ AML cases in which cells were available for gene analysis, all showed germline configuration of immunoglobulin heavy chain and T-cell receptor beta chain genes, while seven of nine B+ AML showed rearrangements of either or both of the genes. Double labeling of the cells with myeloperoxidase and lymphoid markers demonstrated that individual blasts in all the five T+ AML tested were simultaneously expressing myeloperoxidase activity and CD7; however, most blasts in the three B+ AML studied expressed either myeloperoxidase activity or CD10, but not both. In eight of the nine T+ AML tested, the T-cell antigen-positive leukemic blasts were significantly decreased to less than 10%, after in vitro culture with the differentiation-inducing agent phorbol ester. B-cell markers remained positive (> or = 20%) on the cells in the two B+ AML who had the same study. These findings suggested that T+ AML and B+ AML might have different biologic features. Further studies on more patients are needed to clarify this point. PMID- 8483321 TI - Effect of long-term treatment with recombinant human interleukin-3 in patients with myelodysplastic syndromes. AB - In a phase II study, involving nine patients with refractory anemia or refractory anemia with ring sideroblasts, the effects of treatment with recombinant human interleukin-3 (IL-3) on hematopoietic function were assessed. Doses of IL-3 ranging from 60 micrograms/m2 during weeks 1-6 to 125 micrograms/m2 during weeks 7-12 were administered as subcutaneous bolus injections three times per week for 12 weeks. Platelet counts increased in six patients. Platelet increase correlated with stable or decreased serum tumour necrosis factor alpha (TNF-alpha) levels, while an increase of TNF-alpha levels during IL-3 therapy occurred in patients with no change or a decrease of platelet counts. Leukocyte counts increased in two patients and reticulocytes in three, without an effect on hemoglobin levels. Morphological analysis of the bone marrow revealed an expansion of the myeloid compartment in seven of eight evaluable patients, mainly due to stimulation of the precursor cells. No improvement of the in vitro growth of hematopoietic progenitor cells was observed. Sequential cytogenetic analyses indicate that IL-3 treatment does not act preferentially on either the cytogenetically abnormal or the normal clones. These results suggest that long-term treatment with low-dose IL-3 stimulates megakaryopoiesis with increase of platelet counts, but that additional later-acting cytokines probably will be required to augment neutrophil and erythrocyte counts. PMID- 8483322 TI - ABL-BCR mRNAs transcribed from chromosome 9q+ in Philadelphia-chromosome-positive chronic myeloid leukaemia. AB - Polymerase chain reaction amplification of reverse transcription products has demonstrated the presence of abl-bcr hybrid mRNAs in RNA from peripheral blood leucocytes of Philadelphia-chromosome-positive chronic myeloid leukaemia patients; such hybrid mRNAs can contain either of the alternative first exons of c-abl. A survey of 12 CMLs has shown that abl-bcr mRNAs occur in the leucocytes of some, but not all, patients, and that they are present both in chronic-phase and acute-phase leucocytes. PMID- 8483323 TI - Interferon-alpha inducible 2'-5' oligoadenylate synthetase transcripts in lymphoid and myeloid leukemias. AB - Alpha-interferon (IFN) is effective in the treatment of a proportion of patients with hairy cell leukemia (HCL). B-cell chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) and multiple myeloma (MM). One of the proteins induced by IFN is the enzyme 2'-5' oligoadenylate synthetase (2-5 AS). Peripheral blood or bone marrow samples treated with IFN in vitro, or from patients treated with IFN were studied for expression of the different 2-5 AS mRNA transcripts. A total of four normal individuals and 31 patients (nine HCL, five CLL, six MM, nine acute myeloid leukemia (AML) and two T-cell acute lymphoblastic leukemia (T ALL) have been investigated. In normal peripheral blood lymphocytes, only the 1.8 kb transcript was induced with IFN in vitro. In HCL, CLL, and MM all four transcript sizes were induced by IFN in vivo and in vitro. The 1.6 and 1.8 kb forms were equally and predominantly expressed in HCL and B-CLL. On the other hand, the 1.8 kb transcript was predominantly expressed in MM and this increased expression was statistically significant. In acute leukemia, the majority of samples expressed all four transcripts equally but four of eleven samples expressed only the 1.8 kb transcript. These results suggest that the pattern of induction of specific 2-5 AS mRNA transcripts may be related to the underlying disease. Whether these different patterns of 2-5 AS induction have implications for response to IFN treatment, remains to be determined. PMID- 8483324 TI - Inhibition of murine hematopoiesis by CAMAL, an inhibitor of human hematopoiesis. AB - CAMAL (common antigen of myelogenous acute leukemia) is an antigenic preparation isolated in this laboratory from the bone marrow or peripheral blood leucocytes of persons with myeloid leukemias and shown using an immunoperoxidase slide test to be diagnostic of these leukemias. Material further purified from CAMAL preparations, which migrates in the range of 30-35 kilodaltons (kDa) by sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE), which is referred to as P30-35 CAMAL, and was previously shown to be inhibitory to colony formation by progenitor cells from normal healthy human donors in vitro. This inhibitory activity was directed toward neutrophilic granulocyte colonies (CFU-G) in particular. We now report that P30-35 CAMAL is inhibitory to colony formation by murine progenitor cells in vitro. Colonies from P30-35 CAMAL-treated cultures of murine bone marrow cells were reduced in number and in size, an effect similar to that seen in cultures of human cells. As in assays using human cells, murine CFU G appeared to be preferentially targeted by the inhibitory activity of P30-35 CAMAL. In addition, day 10 spleen colony formation was inhibited by P30-35 CAMAL in an ex vivo assay. Hence, the effects of P30-35 CAMAL on murine progenitor cells appear to parallel the effects observed using human cells. These observations support the possibility that CAMAL might be a regulatory protein in hematopoiesis which is conserved between species. PMID- 8483325 TI - Loss of long-term repopulating ability in long-term bone marrow culture. AB - We have studied the maintenance of stem cells with long-term multilineage repopulating ability from murine bone marrow, cultured on a pre-established bone marrow-derived stromal cell layer, both in a qualitative and quantitative way. Female bone marrow cells were cultured for a period of 1-4 weeks and compared with uncultured cells for their ability to establish and maintain a level of 50% chimerism in a sex-mismatched bone marrow transplantation model. Chimerism was determined in nucleated cells using fluorescence in situ hybridization with a murine Y-chromosome-specific probe. We observed a rapid decline in the ability of cultured marrow cells to repopulate the blood, bone marrow, spleen, and thymus of sublethally irradiated male recipients. After 4 weeks of culture only 5% of the long-term repopulating ability of the inoculated bone marrow cells remained. The remaining long-term repopulating cells, however, had similar qualities to establish and maintain long-term engraftment compared to fresh bone marrow, as judged from their ability to give stable chimerism over a period of 6 months. These observations are relevant for the therapeutic applications of long-term bone marrow cultures in purging protocols prior to autologous bone marrow transplantation of acute and chronic myeloid leukemic patients, and for the use of long-term marrow cultures when introducing foreign genetic material in hematopoietic stem cells. PMID- 8483326 TI - In vitro cytotoxic effect of guinea-pig natural killer cells (Kurloff cells) on homologous leukemic cells (L2C). AB - The Kurloff cell (KC) of the guinea-pig develops natural killer cytotoxic activity in heterologous systems. We report in this paper the effective in vitro cytotoxic activity of the KC in a homologous guinea-pig system, i.e. against the guinea-pig target leukemic L2C cells. A dual-color flow analysis of homologous effector-target conjugates, using calcein-labeled KC and hydroethidine-labeled L2C shows a 40% frequency KC-L2C conjugation. The specific cytotoxicity of KC against L2C (78%) was estimated as the target-loss of green fluorescence due to hydrolysed carboxy-fluorescein diacetate after 4 hours at 37 degrees C. We propose that the Kurloff cell could be involved in surveillance against spontaneously arising leukemic cells, and this could be an explanation for the high degree of resistance to spontaneous or experimentally-induced cancers, in the guinea-pig. PMID- 8483327 TI - In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity. AB - In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells. PMID- 8483328 TI - Identification of novel protein-tyrosine phosphatases in a human leukemia cell line, F-36P. AB - Polymerase chain reaction (PCR) was used to identify protein-tyrosine phosphatases (PTPases) in a human leukemic cell line, F-36P. Degenerate primers deduced from the highly conserved amino acid sequences in the catalytic domain of known PTPases were used for amplification. Among 16 clones sequenced, 13 were identical to known PTPases, whereas the other three clones were disclosed to encode novel PTPases. The expression pattern of one of the three newly identified PTPases, designated as F-36-12, was further analysed. In murine tissues, the F-36 12 message was predominantly expressed in brain, kidney, and intestine, and was weakly expressed in heart and thymus. In human hematopoietic cell lines, the F-36 12 message was preferentially expressed in a promyelocytic leukemic cell line, HL60, and two factor-dependent leukemic cell lines, F-36P and F-36E, that are dependent on granulocyte-macrophage colony-stimulating factor or interleukin-3 and erythropoietin, respectively. The transcript was approximately 8 kb long and the message level in HL60 cells was slightly increased at 24 hours and then slowly declined when treated with dimethyl sulfoxide for granulocyte differentiation, while the message level was rapidly decreased when treated with 12-O-tetradecanoylphorbol 13-acetate for monocyte/macrophage differentiation. These results show that several PTPases including three novel ones are expressed in a human leukemic cell line and that the particular PTPase, F-36-12, might be involved in the differentiation process in HL60 cells. PMID- 8483329 TI - Influence of graft-versus-host disease on the eradication of minimal residual leukemia detected by polymerase chain reaction in chronic myeloid leukemia patients after bone marrow transplantation. AB - To evaluate the remission quality of Philadelphia chromosome (Ph)-positive, BCR/ABL-positive CML patients after allogeneic bone marrow transplantation (BMT) we used the polymerase chain reaction (PCR) to detect BCR-ABL specific RNA in addition to Southern blotting, cytogenetic, and hematological investigation. Fifty-five bone marrow samples of 27 patients in clinical remission were studied by PCR, 0.5 to 99 months (median 8 months) after BMT. The median clinical follow up of this cohort of patients is 24 months (1-109) after BMT. BCR-ABL transcripts could be detected in 16 out of 27 patients (59%). Risk factors for minimal residual leukemia (MRD) as defined by PCR were the kind of graft-versus-host disease (GvHD) prophylaxis (patients with T-cell-depleted grafts had a higher rate of MRD in comparison to patients treated with methotrexate/cyclosporin A) and the presence or absence of GvHD after BMT (patients without GvHD had a higher incidence of MRD than patients with GvHD). Moreover, the detection of minimal residual leukemia had prognostic significance. Out of 16 patients with minimal residual leukemia as detected by PCR, four patients relapsed clinically and two further cases relapsed cytogenetically. In contrast none of the patients lacking evidence of minimal residual leukemia relapsed. Serial PCR analysis may prove helpful in deciding about further therapeutic interventions (e.g. interferon therapy or adoptive immunotherapy) before leukaemic relapse becomes manifest after BMT. PMID- 8483330 TI - Detection of trisomy 8 on blood smears using fluorescence in situ hybridization. AB - In this study, fluorescence in situ hybridization (ISH) with an alphoid probe was used for the detection of trisomy 8 on archival blood smears (BS). The results were compared with hybridization experiments performed on methanol/acetic acid fixed cells of cytogenetic preparations (CP) which are widely used for ISH. Five controls and 20 patients with myeloid leukemias were examined. In the controls, CP and BS had the same percentages of cells with two or three fluorescence signals. In 5/20 patients, trisomy 8 was detected both on CP and BS. Two of the patients had 7 to 10% interphase cells with three hybridization signals, indicating the presence of small subclones with trisomy 8; one of the subclones was not detected by G-banding analysis. The remaining 15 patients were disomic for chromosome 8; hybridization results were within the range of the controls both on CP and BS. We conclude that using a chromosome 8 specific alphoid probe, fluorescence ISH to interphase cells can be performed on BS with the same efficiency that is reached on methanol/acetic acid fixed cells of CP. PMID- 8483331 TI - Erythema nodosum associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia. AB - A patient with acute promyelocytic leukemia is presented. During treatment with all-trans-retinoic acid, erythema nodosum developed. Treatment with all-trans retinoic acid was continued, the erythema nodosum resolved with steroid treatment, and a complete remission was attained. This case is the first report of erythema nodosum associated with all-trans-retinoic acid. PMID- 8483332 TI - Successful treatment of veno-occlusive disease of the liver with urokinase in a patient with non-Hodgkin's lymphoma. AB - A 38-year-old man with a non-Hodgkin's lymphoma of intermediate grade malignancy attained partial remission after three courses of CHOP (cyclophosphamide+hydroxydaunorubicin+vincristine+prednisolone). He was assigned to undergo autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of cyclophosphamide and whole body irradiation. Two weeks later he developed veno-occlusive disease (VOD) of the liver. Doppler sonography confirmed the diagnosis showing a reversal of the blood flow in the portal vein. In addition a large thrombus was present in the inferior caval vein. Protein C level was strongly reduced (28%). Because of clinical deterioration intravenous urokinase was started. The transaminases normalised rapidly and the patient showed a dramatic clinical improvement. There were no major bleeding complications. Repeat Doppler sonography showed a normal antegrade flow in the portal vein. This case suggests that a coagulopathy in the hepatic vascular bed might contribute to the development of VOD and that patients with VOD are at risk for other thrombotic complications. Furthermore it shows that urokinase with platelet support can be given safely and effectively to a patient with VOD and severe thrombocytopenia. PMID- 8483333 TI - Involvement of the different members of the NF-kB transcription factor family in B-chronic lymphocytic leukemia. PMID- 8483334 TI - White House health care reform forum. PMID- 8483335 TI - Crisis in community health care on the Eastern Shore. Interview by Edna Quinn. PMID- 8483336 TI - Purine nucleoside phosphorylase: a target for drug design. PMID- 8483337 TI - Peptidomimetics derived from natural products. AB - Although much has been written in recent years about rational drug design, no drug has been designed de novo, that is, without using a natural substrate or inhibitor or screening lead as a starting point. Instead, as we have seen, medicinal chemists continue to depend upon serendipitous discovery of novel biological activities and novel chemical entities for structures on which to begin work. What rational drug design really means at present is rational drug discovery and rational optimization. These result from the application of modern structural and mechanistic biochemistry, and good synthetic chemistry, to obtain structures with the desired spectrum of biological activities. Traditionally, lead compounds were discovered in plant and animal extracts, and more recently in microorganisms and chemical libraries. These traditional approaches continue, but are augmented by advances in molecular biology, which now provide pure proteins in quantity for screening and structure determination, as well as for characterization by modern biophysical methods. Remarkably, x-ray and NMR methods can now provide the most important information needed to design new drugs, that is, the conformations of ligands bound to target proteins. Approaches to identifying possible ligands based only on the knowledge of the enzyme active site are being developed. Some of these, such as CAVEAT, have been recently reviewed. In spite of these impressive gains, de novo design of new drugs will not be achieved until we learn how to logically build specific inhibitors of a target enzyme knowing only the protein sequence of the enzyme or the amino acid sequence of the messenger substances. We have a long way to go, because by this very rigorous definition, even the successful design of a new nonpeptide drug beginning with enzyme-ligand NMR or x-ray structure constitutes rational optimization. However, as this article has illustrated, we have made great progress. Some of the current and futuristic approaches to drug design are shown in Fig. 8. Development of useful enzyme inhibitors, designed by knowing the enzyme catalytic mechanism or discovered by screening for natural inhibitors, is a very successful rational method. Discovery of receptor antagonists by screening protocols is also productive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8483338 TI - Privileged communications: medical confidentiality in late Victorian Britain. PMID- 8483339 TI - Pious physic for the poor: the lost Durham County medical scheme of 1655. PMID- 8483340 TI - Measuring "the social evil": the incidence of venereal disease in interwar Scotland. PMID- 8483341 TI - Henry Fogg (1707-1750) and his patients: the practice of an eighteenth-century Staffordshire apothecary. PMID- 8483342 TI - Illustrations from the Wellcome Institute Library. The life and times of the Myers Collection. PMID- 8483343 TI - ["No" to grades. Impossible, inadequate and dispensable]. PMID- 8483344 TI - [Psychosomatic aspects are completely missed in connection with back pain]. PMID- 8483345 TI - [Who is infected with atypical mycobacterium without having AIDS?]. PMID- 8483346 TI - [Smoking--parents are often bad examples]. PMID- 8483347 TI - [Improve the proposal for a new tobacco law]. PMID- 8483348 TI - [Is diabetes in children caused by cow's milk?]. PMID- 8483349 TI - [The sour stomach of the smoker. Protective mechanisms of the mucosa are more important than the level of acid secretion]. PMID- 8483350 TI - [Good mental health among adopted children from foreign countries]. AB - All 181 families living in one county in southern Sweden who during the period, 1970-77, adopted children via Adoptionscentrum, the largest adoption agency in Sweden, were invited to take part in a study of mental health and identity development; 152 families (84 percent) accepted, a total of 211 adopted youngsters over 12 years of age thus being included in the study. According to the results of interviews with the parents and self-rating instruments administered to the youngsters, their mental health was good. The results were compared with those of an age-matched group of non-adoptive children who had taken part in an epidemiological study using the same investigative methods. The relevance of family factors and age at adoption is discussed. PMID- 8483351 TI - [L-dopa and bromocriptine in Parkinson disease. Early combination therapy has better effect]. PMID- 8483352 TI - [Low number of infections after outpatient surgery. The patients were cared for in the same wards independently of the type of surgery]. PMID- 8483353 TI - [Health risks of gasoline handling. Exposure to benzene can cause leukemia]. PMID- 8483354 TI - [New studies on Alzheimer's disease. Promising therapeutic results with tacrine]. PMID- 8483355 TI - [Clozapine treatment of patients with schizophrenia. Great improvements with regard to symptoms and social life]. PMID- 8483356 TI - [Stop the use of mercury]. PMID- 8483357 TI - [Dandy's phenomenon. Bilateral vestibular loss]. PMID- 8483358 TI - [The man behind the phenomenon: Walter Dandy. A skillful neurosurgeon who went his own way]. PMID- 8483359 TI - [District health care in Zimbabwe. Drought, starvation and HIV are the worst threats]. PMID- 8483360 TI - [Medical audit. Cataract surgery at a private ophthalmologic clinic]. PMID- 8483361 TI - [Consensus on otitis. Answers to an inquiry show changed therapeutic practices]. PMID- 8483362 TI - [Indoctrination. A violation of personal integrity]. PMID- 8483363 TI - Role of subtotal thyroidectomy in the management of the follicular neoplasm of the thyroid. AB - Clinically apparent thyroid nodules affect 4% to 7% of the population in North America. Malignant neoplasms of the thyroid comprise only about 1% of all cancers and are found in only 20% of patients undergoing thyroid surgery for suspected thyroid carcinoma. A follicular neoplasm of the thyroid is the most common histologic finding. During surgery, using frozen-section techniques, it is often difficult to distinguish between a benign and malignant lesion. The diagnosis may be deferred following intraoperative frozen-section examination of tissue or changed on evaluation of embedded tissue. In this series of 1224 thyroidectomies from 1976 to 1990, the pathology data from thyroidectomy surgical specimens submitted to tissue analysis were evaluated. It was found that subtotal thyroidectomy was effective in the management of the follicular neoplasm. This approach significantly reduced the morbidity and complications of patients undergoing thyroidectomy. PMID- 8483364 TI - Facial nerve dysfunction in osteopetrosis. AB - When facial nerve dysfunction occurs in conjunction with one of the rare temporal bone dysplasias, the physician faces a therapeutic dilemma. There is no consensus in the literature regarding the management of facial paralysis or facial spasm under these circumstances. During the past 2 years, four patients were seen with forms of osteopetroses and neurotologic symptoms. A patient with malignant, recessive osteopetrosis and a patient with Engelmann's disease were surgically managed for facial paralysis and facial spasm. The outcome of the treatment is discussed as well as the available literature on this subject. A new complication of facial nerve decompression in children with osteopetrosis is described, as well as appropriate caveats in the management of facial nerve disorders in the osteopetroses. PMID- 8483365 TI - Prognostic significance of sinus histiocytosis in metastatic laryngeal cancer. AB - A histopathologic analysis of regional lymph node specimens in 48 patients with previously untreated squamous cell carcinoma of the larynx was performed to determine which parameters, if any, correlated with 3-year patient survival. The presence of sinus histiocytosis in lymph nodes containing metastatic squamous cell carcinoma was statistically related to survival (P < .007). Multivariate analysis confirmed the independent significance of this variable compared to tumor stage, nodal status, and extracapsular spread from lymph nodes. Previous studies have linked improved survival with an active immunologic response in head and neck cancer patients. However, few studies have examined a homogeneous group of patients who all underwent the same type of treatment. This study's findings support the concept that an active immunologic response in lymph nodes has prognostic significance in squamous cell carcinoma of the larynx. PMID- 8483366 TI - Microbial adherence to and disinfection of laryngoscopes used in office practice. AB - This study reports the appropriate disinfection methods for flexible and rigid laryngoscopes when used in an outpatient setting. This investigation presents evidence that an appreciable number of laryngoscopes are contaminated during use. A brief tap water rinse serves to eliminate gross soil of host origin known to interfere with disinfectant efficacy. Disinfection with 3.2% glutaraldehyde (Cidexplus) for 10 minutes effectively eliminated microbial contaminants. Since potentially harmful microorganisms were included among the more than 100 isolates during our baseline experiments, the need to eliminate bacteria, viruses, fungi, and protozoa from laryngoscopes is obvious and can be attained readily. PMID- 8483367 TI - Squamous cell carcinoma in HIV-positive patients under age 45. AB - Eight patients 45 years of age and under (range, 29 to 45) with squamous cell carcinoma of the head and neck and infection with the human immunodeficiency virus are reported. Primary tumor sites include nasopharynx, oral cavity, oropharynx, and larynx. Probes for the human papillomavirus were positive in two of the patients. Therapy consisted of surgery followed by radiation therapy in five patients, surgery alone in one patient, and radiation therapy in the remaining two patients. Follow-up ranged up to 2 years and revealed four deaths, three patients alive without disease, and one patient recently posttreatment with residual disease. The significance of the presence of the human papillomavirus in these individuals remains to be determined. The incidence of squamous cell carcinoma of the head and neck under age 45 is low, and whether there may be a higher incidence in HIV-positive patients cannot be determined from this small series. PMID- 8483368 TI - The importance of preoperative nasal endoscopy in patients with sinonasal disease. AB - Functional endoscopic sinus surgery (FESS) has popularized the use of telescopes in sinus surgery and has emphasized the importance of nasal endoscopy and computed tomography (CT) in the evaluation of patients with diseases of the nose and paranasal sinuses. Variations in intranasal and sinus anatomy have been implicated in the etiology of chronic and recurrent sinusitis, and CT imaging has become an important diagnostic tool. Despite this, some patients present with symptoms and telescopic examination suggestive of sinonasal disease, yet demonstrate little abnormality on CT scan. The authors reviewed videoendoscopic and CT examinations of 100 consecutive patients with symptoms of sinus disease and found 9% of patients with abnormal telescopic examination in the context of negative CT findings. In those patients whose CT examinations were positive, telescopic nasal endoscopy was especially useful in delineating the type of soft tissue which obscured the area of the middle meatus. In those patients whose CT examinations were negative, telescopic examination demonstrated septal deflections, mucosal edema involving the middle meatus, as well as turbinate and adenoid hypertrophy. These findings demonstrate that telescopic nasal examination is an important diagnostic modality which often yields important information when evaluating patients with sinonasal disease. PMID- 8483369 TI - Lentigo maligna melanoma of the head and neck. AB - Historically, lentigo maligna melanoma has been considered a "favorable" histological type of melanoma, and treatment by wide local excision was considered curative. A retrospective multivariate analysis of 143 head and neck patients with stage I lentigo maligna melanoma was performed from a database of 1067 head and neck patients followed at Duke Medical Center. Fifty-six percent of all lentigo maligna melanomas presented with lesions deeper than 0.76 mm, and 8% presented with stage II or III disease. Recurrent disease occurred in 45% of stage I patients, with a 5-year disease-free interval of 6 years and a median survival time of 10 years. Multivariate analysis demonstrated no significant difference in disease-free interval or survival by histological subtype. The data suggest that treatment should be based on tumor thickness and not histologic subtype. PMID- 8483370 TI - Localization of interleukin-1 in human squamous carcinomas of the head and neck. AB - Recent investigations revealed that interleukin-1 can promote bone resorption by activating osteoclasts. The authors' immunocytochemical studies with monoclonal antibody against human interleukin-1 localized interleukin-1 at the bone resorption site of the squamous carcinomas as well as within the squamous carcinomas. In addition, Western blotting and dot blotting methods were used to isolate interleukin-1 from the extracts of the squamous carcinomas in the head and neck. Finding interleukin-1, a potent bone resorption-stimulating factor, in squamous carcinomas suggests that interleukin-1 might play an important role in the extensive local bone destruction seen in the head and neck patients with squamous carcinomas. PMID- 8483371 TI - Quantitative cytology of nasal secretions under various conditions. AB - Quantitative cytology was performed in nasal secretions of normal control (NC), seasonal allergic rhinitis in season (SAR), perennial allergic rhinitis (PAR), chronic sinusitis with mucoid secretion (MS), and chronic sinusitis with mucopurulent secretion (MPS). The majority of inflammatory cells were neutrophils in NC, MS, and MPS; the majority were eosinophils in SAR and PAR. The concomitant appearance of inflammatory cells in nasal secretions was found, i.e., there were significant correlations between neutrophil and eosinophil counts in MPS, and between eosinophil and basophil counts in SAR. The eosinophil/neutrophil ratio was more than 0.1 in SAR and PAR, but the ratio was less than 0.1 in all NC, all MPS, and in 93% of MS; this indicates that 0.1 in eosinophil/neutrophil ratio is the critical value between allergic and nonallergic nasal diseases. PMID- 8483372 TI - Prognostic value of histopathological parameters in 51 supraglottic squamous cell carcinomas. AB - The prognosis for supraglottic squamous cell carcinomas is difficult to establish. A study of 19 histopathological parameters (14 from the primary tumor and 5 from the lymph node metastases) was undertaken in 51 supraglottic epidermoid carcinomas. All patients were subjected to supraglottic horizontal laryngectomy with bilateral functional neck dissection and postoperative radiotherapy. A discriminant analysis was performed to relate the different histopathological variables to 5-year survival. Capsule rupture and the number of metastatic lymph nodes were the only two parameters significantly related to survival (P < .01). Histopathology (in particular, lymph node metastases) proved more effective in predicting patient evolution than TNM staging. PMID- 8483373 TI - Three-dimensional reconstruction of the temporal bone from a case of E trisomy syndrome. AB - Computer-assisted three-dimensional reconstruction was performed from histologic sections of the left temporal bone removed from a case of E trisomy syndrome. The reconstructions included structures such as the bony and membranous labyrinths, ossicles, ossicular muscles, tympanic membrane, and facial and eighth nerves. The structures could be observed individually or simultaneously in combination. Prominent abnormalities observed in these reconstructions included enlargement of the utricle, absence of the posterior semicircular canal, slight hypoplasia of the cochlea, anomaly of the stapes, abnormally shaped stapedius muscle, abnormal course of the facial nerve, and flattening of the tympanic membrane. The results were useful for the visual and stereoscopic understanding of abnormal configurations and the spatial orientations of these abnormalities. PMID- 8483374 TI - Costochondral pharyngeal implants for velopharyngeal insufficiency. PMID- 8483376 TI - Endoscopic sinus surgery. PMID- 8483375 TI - The role of real-time ultrasonography in an otolaryngology office setting. PMID- 8483377 TI - Auditory brainstem response testing. PMID- 8483378 TI - Tetracaine base topical anesthesia. PMID- 8483379 TI - Chronic ethmoidal sinusitis. PMID- 8483380 TI - Evaluation of tissue ascorbic acid status in different hormonal states of female rat. AB - The distribution pattern of ascorbic acid in the endocrine organs and/or tissues was investigated during various sexual states of female rats to demonstrate a correlation between ascorbic acid concentration and sex hormone activity. The concentration of ascorbic acid was estimated in the plasma, liver, pancreas, thyroid, ovary, adrenal and pituitary of contraceptive steroid treated, bilaterally ovariectomized, sham-operated and normal control animals at four different phases of estrous cycle to delineate a relationship between the level of ascorbic acid in different organs/tissues at various sex hormonal states. Statistically significant changes were observed in the concentration of ascorbic acid in different endocrine organs/tissues following contraceptive steroid treatment, ovariectomy and during the estrous phases. Our results suggest that the concentration of ascorbic acid in the endocrine organs and/or tissues varies during different sexual states of rat. PMID- 8483381 TI - Disturbances in autoregulatory responses of rat pial arteries by sulfonylureas. AB - It was aimed to test the role of ATP-sensitive K+ channels in the autoregulatory response of cerebral arterioles in vivo. Changes in pial arterial caliber (mean, 43.2 +/- 2.3 microns in diameter) in response to changes in systemic arterial blood pressure (mean, 104.3 +/- 1.4 mmHg) were observed directly through closed cranial windows in anesthetized normotensive rats. During superfusion with vehicle, pial arterial caliber automatically increased in response to hypotension induced by arterial bleeding into a reservoir and decreased on reverse of arterial blood pressure by infusion of blood. After pretreatment with sulfonylureas, glibenclamide (1 and 3 microM) and glipizide (30 and 100 microM), arteriolar dilatation and constriction observed during hypotension and its reverse were disturbed. A similarity was evidenced when hypotension was induced by sodium nitroprusside (750 nmol kg-1min-1, i.v.). Cromakalim, a K+ channel opener, exerted a concentration-dependent vasodilatation of the pial artery and its effect was antagonized by glibenclamide. These data suggest that the endogenous glibenclamide-sensitive K+ channel opener is involved in the modulation of cerebral microvascular autoregulation. PMID- 8483382 TI - Changes in striatal dopamine metabolism during the development of morphine physical dependence in rats: observations using in vivo microdialysis. AB - The present study examined the effect of prolonged morphine treatment on striatal dopamine (DA) release and metabolism, during the initial phase of the development of morphine dependence. Sprague-Dawley rats were implanted with chronic guides for microdialysis of the striatum. Morphine (two 75-mg pellets, subcutaneous implant) or placebo was given (12 hr) to pentobarbital anesthetized animals. Following recovery from anesthesia, morphine physical dependence was verified by the naloxone-evoked abstinence syndrome. Morphine produced significant increases in the dialysate level of DA nad its metabolites (DOPAC and HVA) above baseline compared to placebo treatment. HVA levels began to increase immediately following morphine administration, whereas DA and DOPAC levels began to increase after a latency of one and three hr, respectively. Morphine effects on striatal DA metabolism included changes in the metabolic disposition of DA. Increases in HVA concentration accompanied increases in DOPAC concentration up to a threshold value of DOPAC efflux; further increases in DOPAC level were associated with decreases in HVA level. These in vivo data suggest that morphine-induced changes in the regulation of striatal dopaminergic function may be an important component of the development of physical dependence. PMID- 8483383 TI - Regulation of the dynamic properties of platelet plasma membrane by intracellular sodium ions. AB - Our previous experiments in human and rat platelets demonstrated that the absence of extracellular Na+ increased the fluorescence anisotropy of TMA-DPH (trimethylamino-diphenylhexatriene, probe preferentially incorporated into the outer leaflet of the plasma membrane). Here we investigated further the in vitro effects of Na+ ions on membrane dynamic properties. Na(+)-dependent changes were reversible and they required about 10-20 min to be induced. They were specifically located in the TMA-DPH environment because they were not observed with diphenylhexatriene (probe non-selectively incorporated into all hydrophobic domains of the cell). To evaluate the possible influence of the intracellular Na+, the effects of sodium replenishment, monensin, ouabain and thrombin on TMA DPH anisotropy were measured. A rise in intracellular Na+ above the physiological level was associated with unchanged or slightly decreased TMA-DPH anisotropy whereas its decrease was accompanied by a pronounced rise in TMA-DPH anisotropy. Our data indicate that the changes in intracellular Na+ concentration, rather than those in extracellular Na+ concentration, are responsible for the alterations in platelet membrane fluidity probed by TMA-DPH. PMID- 8483384 TI - Manganese exposure to PC-12 cells alters triacylglycerol metabolism and promotes neurite outgrowth. AB - Exposure of PC-12 cells to MnCl2 (10-100 microM for 1 to 3 days) resulted in both morphological and metabolic changes as indicated by promotion of neurite outgrowth and an increased incorporation of labeled fatty acids (14:0, 18:1 and 20:4) into triacylglycerols (TG). Cells prelabeled with [14C]arachidonic acid (AA) showed a time-dependent decrease in labeled TG, and the rate of decline was inhibited by Mn (100 microM). In the pulse-chase type of study, the decrease in the proportion of labeled TG as well as labeled phosphatidylcholine (PC) was marked by an increase in labeled phosphatidylinositol and phosphatidylethanolamine. These results support previous notion that TG plays an important role in channeling the fatty acid nutrients for biosynthesis of membrane phospholipids. Thus, the Mn-induced inhibition of the ability to transfer TG fatty acids to other lipids in PC-12 cells may be an underlying cause for the observed morphological changes. PMID- 8483385 TI - The effects of alcohol on murine macrophage function. AB - Animal models used to measure the effects of alcohol on lymphoid cells and their functions provide useful ways to evaluate the multisystem effects of this substance. The effects of ethanol ingestion on the function of murine peritoneal macrophages (M phi) was evaluated. Both the production of reactive oxygen intermediates (ROI) and the ingestion of foreign particles (phagocytosis) were studied. Mice were pair fed ad libitum a nutritionally complete liquid diet containing 7% v/v ethanol or a calorically balanced control diet. Two regimens were employed for the administration of the diets. One regimen represented "binge" drinking (short term-4 days) while the other represented "chronic" consumption (long term-14 days). Following the short term administration of the diets, an increase in the respiratory burst (RB), as well as a decrease in phagocytosis, were observed with M phi from the ethanol fed mice. The decrease in phagocytosis, was noted using either in vitro or in vivo methods. Results observed after long term administration indicated no significant change in the RB or in in vitro phagocytosis between the ethanol and control groups. Phagocytosis measured in vivo, however, was decreased in M phi from ethanol fed mice following long term administration. These results indicate an alteration in murine peritoneal M phi function following short term an long term administration of alcohol. PMID- 8483386 TI - Comparative effect of nifedipine and S-adenosylmethionine, singly and in combination on experimental rat liver cirrhosis. AB - An experimental rat liver cirrhosis, by means of carbon tetrachloride and ethanol during 8 weeks, was employed to assay the effect of Nifedipine (a calcium antagonist blocker), S-Adenosylmethionine (a precursor of glutathione); singly and in combination on rat liver cirrhosis. A slight decrease of cirrhosis (N.S.) was observed with the pharmacological therapy employed singly. The combination therapy (Nifedipine+S-Adenosylmethionine) significantly inhibited liver cirrhosis (p < 0.01). PMID- 8483387 TI - Characterization of a peripheral vanilloid (capsaicin) receptor in the urinary bladder of the rat. AB - Specific binding of [3H]resiniferatoxin (RTX) is thought to represent the vanilloid (capsaicin) receptor. In the present study, we have used this binding assay to identify for the first time a vanilloid receptor in the periphery and to compare it to central vanilloid receptors present in dorsal root ganglia (DRG) as well as in spinal cord of the rat. Rat urinary bladder membranes bound [3H]RTX with a Kd of 30 +/- 4 pM and a Bmax of 65 +/- 14 fmol/mg protein; the corresponding values were 19 +/- 3 pM and 104 +/- 14 fmol/mg protein in DRG, and 16 +/- 3 pM and 50 +/- 9 fmol/mg protein in spinal cord. Capsaicin inhibited [3H]RTX binding to membranes from urinary bladder, spinal cord, and DRG with similar potency (Ki values were 0.5 +/- 0.1 microM, 0.3 +/- 0.1, and 0.6 +/- 0.1 microM, respectively). Interestingly, [3H]RTX bound to urinary bladder in a non cooperative fashion in contrast with the apparent positive cooperativity of [3H]RTX binding in both DRG and spinal cord (cooperativity index = 1.8 and 1.7, respectively). This finding suggests heterogeneity in the properties of the vanilloid receptors in the rat. PMID- 8483388 TI - Catalytic activity and immunohistochemical localization of flavin-containing monooxygenase in rat kidney. AB - The presence of flavin-containing monooxygenase activity was examined in rat kidney microsomes using N,N-dimethylaniline and methimazole as substrates. Western immunoblot analysis using antisera to porcine liver and rabbit lung flavin-containing monooxygenase indicated immunological cross-reactivity between rat kidney, porcine liver and rabbit lung flavin-containing monooxygenase. Immunohistochemical studies using antisera to rabbit lung flavin-containing monooxygenase demonstrated localization of this enzyme in the proximal and distal convoluted tubules of the renal cortex, the collecting ducts in the renal medulla, but not the glomeruli. This observation indicates the colocalization of flavin-containing monooxygenase and cytochrome P-450 in the metabolically active and absorptive compartment of the renal parenchyma. PMID- 8483389 TI - Effect of maternal adrenal deprivation on the content of catecholamines in fetal brain. AB - Previous studies performed in our laboratory showed the importance of the effects that the absence of maternal adrenal hormones have on fetal brain. In the present study we investigated the effect of adrenal deprivation during gestation on the fetal catecholamines development in several cerebral areas. Fetuses from both control and adrenalectomized mothers from the first day of gestation were removed on the 20th embryonary day. Plasma corticosterone levels were significantly lower in the maternal serum of adrenalectomized rats, while the contents were non significantly higher in the adrenalectomized-mothers group of fetuses. Catecholamine contents in diencephalon, metencephalon, mesencephalon and telencephalon were measured by HPLC-ED. The results obtained showed that when the development of the catecholaminergic systems was previous enough to the fetal adrenal function, and under maternal adrenal deprivation conditions, the lack of corticosterone promotes an increase in the level of the catecholamines, as observed in the diencephalic NA, the earlier in maturational process. In those areas where the maturation starts at the same time than the fetal adrenal hypersecretion, no changes were observed. In the cortex, where both DA and NA develop later, the corticosterone produces an inhibition in the proliferation of the catecholaminergic neurons, showing decreased telencephalic levels of both catecholamines. PMID- 8483390 TI - Metallothionein and glutathione as determinants of cellular retention and extrusion of cadmium and mercury. AB - This work explored cellular trapping and extrusion of Cd and Hg in epithelial cells, with special emphasis on the jejunal mucosa. Important determinants of these processes are the concentration, diffusibility and relative metal affinities of a variety of cellular metal-binding compounds including metallothionein (MT). As predicted from the known properties of MT, this protein can compete with other sulfhydryl compounds for Cd but not for Hg; this is illustrated by the observation that glutathione (GSH) stimulates extrusion of only Hg. Similar factors can help explain why, in spite of its tighter binding by MT, Hg has a shorter biological half-life in renal cortex than does Cd. Metal extrusion from cells presumably involves movement of diffusible complexes such as HgGSH. PMID- 8483391 TI - Antisecretory and cytoprotective doses of enprostil do not alter gastric mucosal blood flow. AB - Prostaglandins of the E series are antisecretory and cytoprotective. Cytoprotection occurs in the deep but not superficial gastric mucosa. It has been hypothesized that the mechanism of cytoprotection involves increased gastric mucosal blood flow (GMBF). However, basal and stimulated gastric mucosal blood flow is greater in the deep than superficial corpus mucosa. The purpose of this study was to investigate the effect of a prostaglandin E2 analog, enprostil, on GMBF in the deep mucosa, where cytoprotection is observed, in both antisecretory and cytoprotective doses. Gastric mucosal blood flow in the deep half of the mucosa was measured by the hydrogen gas clearance method before, during and after intragastric perfusion of enprostil, 0.1-100 micrograms/kg, in urethane anesthetized rats. Enprostil did not alter GMBF in any of the doses tested. Therefore, the cytoprotective action of enprostil is mediated by factors other than a primary increase in GMBF. PMID- 8483392 TI - Neutral aminopeptidase activity levels during the estrous cycle and the pregnancy in the hypothalamus and the pituitary of the rat. AB - Neutral aminopeptidase activity levels during the estrous cycle and pregnancy, in the hypothalamus and the pituitary of experimental animals, was studied in this research. The cyclic stages were the estrous, diestrous and proestrous (at morning and afternoon). The pregnancy phases were the 2nd, 7th, 14th and 20th day postinsemination. The parturition day was also studied. The higher cyclic enzyme levels were found in the proestrous stage (afternoon). No differences between estrous and diestrous were observed. During pregnancy, there was a rise at 7th and 14th day, with a decrease in the 20th day. In the hypothalamus, significant increases after parturition were shown, the latter not being observed in the pituitary. In general, the changes seem to be parallel to those of the luteinizing hormone. PMID- 8483393 TI - Precocious puberty in chicks (Gallus domesticus) induced by central injections of neuropeptide Y. AB - The objective of the study was to determine the role of neuropeptide Y (NPY) and biogenic amines on the onset of puberty in birds. Male broiler chicks were administered chronic intracerebroventricular (ICV) injections of 5 micrograms NPY which produced sexually precocious chicks, determined by advanced secondary sex characteristics. One or two weeks following the beginning of a series of NPY injections, the preoptic area (POA), bed nucleus of the pallial commissure (nCPa), paraventricular nucleus (PVN), and median eminence (ME) were analyzed for biogenic amines. Levels of L-dopa, the precursor of dopamine (DA) were increased within the ME of chicks that responded to treatments by showing advanced sexual maturation when an amino acid decarboxylase blocker was administered prior to sacrifice. The PVN of respondents showed several changes in biogenic amines, while the nCPa displayed a biogenic amine metabolite of unknown identity which was significantly lower in respondent chicks. In contrast to mammals, L-dopa was detectable within the nCPa, PVN, and ME regardless of whether an enzymatic blocker of amino acid decarboxylase was administered to chicks prior to sacrifice. Results suggest that increased brain levels of NPY and DA, the latter specifically occurring within the ME, are associated with the onset of puberty. Due to the several significant differences found in biogenic amino levels within the PVN of respondent chicks, this nucleus, similar to the ME may be a highly active and integrative neural structure during the onset of puberty in chicks. PMID- 8483394 TI - Classic versus sequential diagnostic support for chronic nonspecific respiratory diseases. AB - The authors discuss two approaches to assisted medical diagnosis of chronic nonspecific respiratory diseases, Bayes-Fisher linear discrimination and a decision tree based on the linear discriminant functions of the individual nodes. Only the two most discriminative variables obtained for differentiation of groups at individual nodes are used for the node subclassification. They are the four linguistic variables cough, character of dyspnea, physical examination of the chest, and x-ray examination of the chest obtained by conversion of discrete features. No laboratory finding is used. The tree classifier simulates a physician's thought process. Results with multigroup linear discrimination on the same four variables for both a reclassification and a cross-validation technique were comparable to the tree-scheme outcomes. The tree classifier lends itself to simple graphic presentation, the patient being created as a point in the plane of the two most discriminative variables without the need for mathematical formulas and posterior probabilities. The classification errors that appear in the chronic bronchitis group can be easily corrected using an additional variable, smoking index. PMID- 8483395 TI - Teaching clinical decision making in a family practice clerkship. AB - Limited health care resources and other social factors are making clinical decision making (CDM) a necessary subject of study for medical students. However, CDM material is technical and could be perceived by students as arcane. This study evaluated student attitudes toward a CDM module imbedded in a third-year medical student (MSIII) family medicine clerkship. A survey instrument was used for the evaluation and included a within-subject check for response consistency. The results show that MSIIIs feel that technical CDM material is within their grasp and that it is relevant to their day-to-day care of patients. PMID- 8483396 TI - A multiattribute-utility-function approach to weighing the risks and benefits of pharmaceutical agents. AB - Both the selection of doses of pharmaceutical agents and comparisons between pharmaceutical agents have long been based on the nonquantified concept of the risk-benefit ratio. Though useful, this concept implies a data comparison that is difficult to make: the toxicity versus the efficacy of a drug compound. This research demonstrates an approach for weighing risks and benefits by combining utility functions for human efficacy and toxicity with animal and laboratory toxicity information to develop an overall multiattribute utility function for an ophthalmic pharmaceutical agent, I-bunolol, intended for the treatment of glaucoma. With this multiattribute function and a small portion of the published data available for this drug, the expected utilities for six doses (including a control) could be compared and the value of this approach in drug-dosage selection demonstrated. PMID- 8483397 TI - Using treatment-tradeoff preferences to select diagnostic strategies: linking the ROC curve to threshold analysis. AB - Selection of optimal diagnostic strategies depends on the accuracy of diagnostic tests, the prevalence of disease, and the relative benefits and harms resulting from test/treatment choices. One can characterize diagnostic strategies according to their net benefit-to-harm ratios. Within the framework of expected-utility theory, the benefit-to-harm ratio is equivalent to the marginal tradeoff between erroneous and correct treatment choices. Consequently, a physician can identify his or her preferred strategy by asking the question: "How many additional treatment errors am I willing to make in order to treat one additional person correctly?" Family physicians were asked to indicate their lowest and highest acceptable tradeoff ratios in a survey about streptococcal pharyngitis. All 53 respondents indicated uncertainty about their preferred treatment-tradeoff ratios. For 58% of respondents, the midpoints of the acceptable range of tradeoff ratios corresponded to generally accepted diagnostic strategies: 1) test all or 2) treat if classic, test all others. In contrast, previously published patient utilities yield a treatment-tradeoff ratio that corresponds to the strategy of treating all cases. The analysis illustrates the linkage between the optimal operating point on a receiver operating characteristic (ROC) curve and the selection of a preferred diagnostic strategy based on treatment thresholds derived from benefit-to-harm ratios. The survey results indicate that physicians can respond directly to questions assessing their preferences for such treatment thresholds. Differences between patients and physicians have significant impacts on choices of test and treatment strategies. PMID- 8483398 TI - Test-retest reliabilities of two treatment-preference instruments in measuring utilities. AB - The authors assessed the test-retest reliabilities of two treatment-preference instruments recently applied to the measurement of the utilities of health states after different treatment modalities for cancer. The first instrument measures the strengths of preferences concerning a choice between a wait-and-see policy, and treatment with radiotherapy after an initial surgical breast-conserving procedure for early breast cancer. The second measures the strengths of preferences concerning a choice between two hypothetical surgical treatment outcomes in cancer of the rectum with different probabilities of expected five year survival. Both measure the strength of a subject's treatment preference given probabilities of treatment-related costs and benefits. The subjects were radiotherapy technicians (n = 20) and cancer patients (n = 20) who were interviewed in weeks 2 and 4 of radiotherapy. The test-retest reliabilities of both instruments were inconsistent and moderately high, with Spearman's rank correlations ranging from 0.38 to 0.81 and weighted kappas ranging from 0.38 to 0.69. To investigate whether the start of treatment with radiotherapy influenced the utilities that patients assigned to health states, the same procedure was applied in another, comparable, group of patients with cancer (n = 20). For this group, the first assessment was made prior to the start of treatment and the second during the second week of radiation therapy. The scores of this group of patients indeed appeared to be less stable than the scores of the patients assessed in weeks 2 and 4 of radiotherapy. However, the instability of the scores could have been the result of test bias. PMID- 8483399 TI - Integrating stratum-specific likelihood ratios with the analysis of ROC curves. AB - Data used to construct receiver operating characteristic (ROC) curves and to calculate the area under the curve (ROC AUC) can be used to derive stratum specific likelihood ratios (SSLRs) with their 95% confidence intervals (95% CIs). The purpose of this study was to determine whether useful information can be obtained by adding SSLRs to the analysis of ROC curves. The authors analyzed four previously reported sets of data: 1) serum creatine kinase (SCK) for diagnosing acute myocardial infarction (AMI) in the coronary care unit (CCU); 2) SCK in the evaluation of chest pain in the emergency center (EC); 3) four predictor variables in the diagnosis of strep throat; and 4) the ordinal assessment of computed tomographic (CT) images. Use of SCK in the CCU produced four strata that had posttest probabilities that were highly discriminating, whereas SCK in the EC resulted in only two strata with limited discriminating ability. In either study the cutpoint at which the SSLR changed from less than to greater than 1.0 was higher than the reported upper normal for the test, thereby quantitating spectrum bias. The maximum number of strata of predictor signs and symptoms for strep throat was three rather than the five used in previous studies. With a larger sample size or pooling, four strata could probably be developed. With CT images, "definitely normal," "probably normal," and "questionable" were collapsed to one negative stratum. "Probably abnormal" became the true "questionable" stratum and "definitely abnormal" was the only positive stratum. The authors conclude that additional useful information is obtained by deriving stratum-specific likelihood ratios as part of the analysis of an ROC curve. PMID- 8483400 TI - A measure of mortality risk for elderly patients with acute myocardial infarction. AB - The objective of this study was to derive and validate a simple scoring system that predicts risk of short-term mortality in elderly patients hospitalized with acute myocardial infarction (AMI) and to compare this derived score with the MedisGroups admission severity score. A myocardial infarction severity score (MISS) was derived from a database of clinical information abstracted using MedisGroups and follow-up information on 30-day mortality status. The MISS was validated and compared with the MedisGroups Admission Severity Groups (ASGs) in a separate database. The derivation set included 2,037 Medicare patients 65 years old or older with confirmed AMI who were randomly selected from patients discharged from hospitals in seven states during 1985. The validation set consisted of 6,323 patients from the 1988 MedisGroups comparative database who were at least 65 years of age and had confirmed AMI. Multivariate logistic regression analysis found a set of nine abnormal patient characteristics that independently predict 30-day mortality. There was good agreement between mortality rates predicted by the logistic model and observed mortality rates in the validation population. This regression model was then simplified to an additive score where eight of the characteristics were weighted as one point and one characteristic was weighted as two points. The MISS is the sum of the points for each patient. In the validation dataset, the 1,373 patients with the lowest MISS scores had a mortality rate of 4.6% and the 400 patients with the highest MISS scores had a mortality rate of 64%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483401 TI - Stability of time-tradeoff utilities in survivors of myocardial infarction. AB - To investigate whether time-tradeoff utilities of survivors of myocardial infarction change over time and whether changes in utilities correlate with changes in functional status, the authors conducted serial interviews using a time tradeoff and three measures of functional status in a cohort of 67 patients who had recently had myocardial infarction. The patients were also asked to rate their overall health on a rating scale and were asked about chest pain, exercise status, and employment status. Each patient was interviewed two to five times over one and a half years. The mean (95% CI) time-tradeoff score for all patients was 0.88 (0.84, 0.93). Over a mean interval of 8.4 months, 28 (42%) patients changed Karnofsky scores, 28 (42%) changed Specific Activity Scale classes, and 11 (16%) changed New York Heart Association classes, with most changes representing improvements in functional status. Scores on the rating scale improved by a mean (95% CI) of 0.06 [(0.03, 0.10); p < 0.002], but scores on the time tradeoff remained stable, with a mean (95% CI) change of 0.03 [(-0.02, 0.08); p = NS]. Changes in time-tradeoff scores did not correlate with changes in Specific Activity Scale classes (Kendall's tau = 0.21), New York Heart Association classes (tau = -0.02), or Karnofsky scores (tau = 0.14); with changes on the verbal rating scale (R = 0.20); with changes in chest pain status (tau = 0.05), exercise status (tau = 0.11), or employment status (tau = 0.11); or with interim hospitalizations (tau = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483402 TI - Assessing the accuracy of physician estimates. PMID- 8483403 TI - Risks in utility assessment and risks of medical interventions. PMID- 8483404 TI - Using age-specific rates in a Markov model. PMID- 8483406 TI - Reanalyzing data. PMID- 8483405 TI - Commentary: fine-tuning life-expectancy calculations using Markov processes. PMID- 8483407 TI - The descriptive epidemiology of health-state values and utilities. PMID- 8483408 TI - The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. AB - The Beaver Dam Health Outcomes Study (BDHOS) is an ongoing longitudinal cohort study of health status and health-related quality of life for a random sample of adults (age range at interview was 45 to 89 years; mean = 64.1, SD = 10.8) in a community population. In a face-to-face interview lasting approximately an hour, each participant responds to several batteries of questions. Included are a history of chronic medical conditions, current medications, and past surgeries; the SF-36 (a general health-status questionnaire); the Quality of Well-being index; self-rated health status on a five-point scale from "excellent" to "poor"; and evaluation of current health using the method of time tradeoffs. The authors present results from 1,356 interviews on these four principal measures, reporting mean scores by sex, by age, and for persons reporting being affected by various medical conditions. They believe data from the BDHOS will provide researchers and policy makers a reference collection of vital statistics for health-related quality of life. Additionally, the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS. PMID- 8483410 TI - Changes in nurse licensure exam. PMID- 8483409 TI - A research utilization workshop. PMID- 8483411 TI - 40th annual meeting of the American College of Sports Medicine. Seattle, Washington, June 2-5, 1993. Abstracts. PMID- 8483412 TI - The Klebsiella pneumoniae nifJ promoter: analysis of promoter elements regulating activation by the NifA promoter. AB - The nifJ and nifH promoters of Klebsiella pneumoniae are divergently transcribed sigma 54-dependent promoters that are positively activated by the NifA protein. NifA binds to upstream activator sequences (UASs), usually located 60-200 bp upstream of the start of transcription. Bound NifA is presented to the RNA polymerase-sigma 54 complex (E sigma 54) via DNA loop formation, mediated by the binding of integration host factor protein (IHF) between E sigma 54 and NifA. The nifJ promoter sequence contains three potential NifA binding sites (UAS1, 2 and 3) and two potential RNA polymerase-sigma 54-binding sites (downstream promoter elements, DPEs 1 and 2). DPE2 is located 420 bp into the coding region and DPE1 overlaps UAS1 by 5 bp. Mutational and footprinting analyses have shown efficient activation of the nifJ promoter requires that NifA is bound at UAS 2 and 3. Transcription is initiated at DPE1. Only a weak interaction of NifA with the UAS overlapping DPE1 was detected. Footprints demonstrated that E sigma 54 forms a closed complex at DPE1 but not DPE2 and that bound E sigma 54 closely approaches the -15 region of DPE1. Stimulation of nifJ promoter activity by IHF was not as great as that observed for other nif promoters. In the absence of IHF nifH promoter sequences stimulated activation of the nifJ promoter. This appeared to require NifA bound at the nifH UAS. Thus, one additional role of IHF may be to partition NifA between the two promoters by constraining the topology of the DNA. PMID- 8483413 TI - The Fis protein: it's not just for DNA inversion anymore. PMID- 8483414 TI - Cloning, nucleotide sequence determination and expression of the genes encoding cytochrome P-450soy (soyC) and ferredoxinsoy (soyB) from Streptomyces griseus. PMID- 8483415 TI - Molecular analysis of spv virulence genes of the Salmonella virulence plasmids. AB - Genes on an 8 kb region common to the virulence plasmids of several serovars of Salmonella are sufficient to replace the entire plasmid in enabling systemic infection in animal models. This virulence region encompasses five genes which previously have been designated with different names from each investigating laboratory. A common nomenclature has been devised for the five genes, i.e. spv for salmonella plasmid virulence. The first gene, spvR, encodes a positive activator for the following four genes, spvABCD. DNA sequence analysis of the spv genes from Salmonella typhimurium, Salmonella dublin, and Salmonella choleraesuis demonstrated extremely high conservation of the DNA and amino acid sequences. The spv genes are induced at stationary phase and in carbon-poor media, and optimal expression is dependent on the katF locus. The virulence functions of the spv genes are not known, but these genes may increase the growth rate of salmonellae in host cells and affect the interaction of salmonellae with the host immune system. PMID- 8483416 TI - Specific binding sites in the alcR and alcA promoters of the ethanol regulon for the CREA repressor mediating carbon catabolite repression in Aspergillus nidulans. AB - The CREA repressor responsible for carbon catabolite repression in Aspergillus nidulans represses the transcription of the ethanol regulon. The N-terminal part of the CREA protein encompassing the two zinc fingers (C2H2 class family) and an alanine-rich region was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase. Our results show that CREA is a DNA-binding protein able to bind to the promoters of both the specific trans-acting gene, alcR, and of the structural gene, alcA, encoding the alcohol dehydrogenase I. DNase I protection footprinting experiments revealed several specific binding sites in the alcR and in the alcA promoters having the consensus sequence 5'-G/CPyGGGG-3'. The disruption of one of these CREA-binding sites in the alcR promoter overlapping the induction target for the trans-activator ALCR results in a partially derepressed alc phenotype and derepressed alcR transcription, showing that this binding site is functional in vivo. Our data suggest that CREA represses the ethanol regulon by a double lock mechanism repressing both the trans-acting gene, alcR, and the structural gene, alcA. PMID- 8483417 TI - Involvement of the RNA polymerase alpha subunit C-terminal region in co-operative interaction and transcriptional activation with OxyR protein. AB - The role of the alpha subunit of Escherichia coli RNA polymerase in transcription activation by the OxyR protein was investigated using in-vitro-reconstituted RNA polymerase containing alpha subunits carrying C-terminal truncations or an amino acid substitution. Mutant RNA polymerases failed to respond to transcription activation of the E. coli OxyR-dependent promoters. DNase I footprinting analysis indicates that the OxyR protein exerts a co-operative effect on the binding of wild-type RNA polymerase, but not the mutant RNA polymerases, to the katG promoter. Together, these results suggest that direct protein-protein contact between the OxyR protein and the C-terminal contact site I region of the RNA polymerase alpha subunit plays an essential role in transcription activation at the OxyR-dependent promoters. PMID- 8483418 TI - Organization of Lrp-binding sites upstream of ilvIH in Salmonella typhimurium. AB - Lrp, a major regulatory protein in Escherichia coli, controls the expression of numerous operons, including ilvIH. Lrp binds to six sites upstream of ilvIH, and Lrp binding is required for ilvIH expression. We show here that an Lrp-like protein is also present in Salmonella typhimurium. This protein can bind both E. coli and S. typhimurium ilvIH DNA, as can E. coli Lrp. Methidiumpropyl-EDTA footprinting studies were performed with purified E. coli Lrp and S. typhimurium ilvIH DNA. Six binding sites were defined, three of them being similar to corresponding sites in E. coli, and three being organized differently. A consensus derived from six S. typhimurium sites is compatible with that derived from a similar analysis of E. coli sequences. PMID- 8483419 TI - Positive transcriptional control of mry regulates virulence in the group A streptococcus. AB - Transcription of the antiphagocytic M protein in the group A streptococcus (Streptococcus pyogenes) is environmentally regulated in response to CO2 and requires Mry, a trans-acting positive regulatory protein. We have examined the role of Mry in environmental regulation by analysing the factors that regulate expression of the gene that encodes Mry (mry). By employing a strategy that utilizes integrational plasmids, it was found that expression of mry requires the participation of DNA sequences that extend 473 base pairs upstream of the Mry coding region. Transcription of mry, as analysed in S1 nuclease protection assays, is initiated from two separate promoters located within this extended regulatory region. Construction and analysis of transcriptional fusions between the mry promoters and a promoterless chloramphenicol acetyltransferase gene demonstrated that mry is autoregulated and environmentally regulated in response to the level of CO2. These data suggest a model for the regulation of virulence in S. pyogenes where positive transcriptional control of mry in response to environmental stimuli regulates the expression of the M protein. PMID- 8483420 TI - Molecular characterization of the enniatin synthetase gene encoding a multifunctional enzyme catalysing N-methyldepsipeptide formation in Fusarium scirpi. AB - The gene encoding the multifunctional enzyme enniatin synthetase from Fusarium scirpi (esyn1) was isolated and characterized by transcriptional mapping and expression studies in Escherichia coli. This is the first example of a gene encoding an N-methyl peptide synthetase. The nucleotide sequence revealed an open reading frame of 9393 bp encoding a protein of 3131 amino acids (M(r) 346,900). Two domains designated EA and EB within the protein were identified which share similarity to each other and to microbial peptide synthetase domains. In contrast to the N-terminal domain EA, the carboxyl terminal domain EB is interrupted by a 434-amino-acid portion which shows local similarity to a motif apparently conserved within adenine and cytosine RNA and DNA methyltransferases and therefore seems to harbour the N-methyl-transferase function of the multienzyme. PMID- 8483421 TI - In vitro transcription in Chlamydia psittaci and Chlamydia trachomatis. AB - Extracts of Chlamydia psittaci and Chlamydia trachomatis were used to transcribe molecularly cloned chlamydial genes in vitro. The extracts were prepared by lysing reticulate bodies, obtaining the 10,000 x g centrifugation pellet, and eluting RNA polymerase from the pellet by treatment with 2M KCl to yield a fraction designated SS2. Some in vitro transcription was initiated from non chlamydial promoters and a small amount of transcription was from endogenous DNA template in SS2. However, optimal transcription from exogenous templates required chlamydial promoter sequences, and primer extension analysis indicated that chlamydia promoter-specific in vitro transcription was initiated from the same start sites recognized in vivo. A monoclonal antibody that was generated against Escherichia coli sigma 70 and which immunologically cross-reacts with C. trachomatis sigma 66 inhibited in vitro transcription of vector and cloned chlamydial DNA, suggesting that transcriptional initiation in the SS2 fraction is mediated by sigma 66. An in vitro transcription assay based on detection of transcripts of specific lengths was applied to the chlamydial system; this assay and others described here should be useful in defining chlamydial promoters and other transcriptional regulatory elements. PMID- 8483422 TI - A positive feedback loop controls transcription of the spoOF gene, a component of the sporulation phosphorelay in Bacillus subtilis. AB - The spo0F gene of Bacillus subtilis encodes a protein that functions as a secondary messenger in a phosphorelay system controlling the initiation of sporulation. Transcription of the spo0F gene was known to be dependent on an intact gene for the transcription regulator Spo0A. In vitro footprint analysis revealed that Spo0A protein bound to two locations in the spo0F promoter region. Deletion of a 40 bp region upstream of one of the promoters (P2) abolished the activation of spo0F expression that occurs at the onset of stationary phase and sporulation. This 40 bp region contains a Spo0A-binding site. These observations are consistent with a hypothesis that Spo0A binding to this region is responsible for activating spo0F transcription. Additionally, Spo0A binding at a downstream site could modulate the level of this activation. Since Spo0F protein is required for the formation of Spo0A-P (the form needed for transcriptional activation) a positive feedback loop controls transcription of spo0F. PMID- 8483423 TI - Translation across the 5'-splice site interferes with autocatalytic splicing. AB - The bacteriophage T4 nrdB gene, encoding the ribonucleotide reductase small subunit, contains a self-splicing group IA2 intron with an ochre codon in frame with the preceding exon sequence. The stop codon was changed to an amino acid codon and splicing efficiency was compared with that of the wild type in the presence and absence of translation. In vivo the mutant has a much lower efficiency for producing a mature transcript than the wild type. Also, the relative production of the full-length translation product is correspondingly lower in the mutant than in the wild type. These results confirm the importance of the stop codon, which spans the splice site of the nrdB intron. The occurrence of stop codons in 56 group I introns in protein-encoding genes was investigated. In 33 of those translation is terminated upstream of the first common elements of the catalytic core, of group I introns. In the rest translation is terminated in intron regions outside the heart of the catalytic core, with one exception. Our observations suggest that in situations where transcription and translation are coupled events there has been an evolutionary pressure to preserve stop codons in the 5'-region of these introns or to prevent translational termination from occurring in vital parts of the introns. PMID- 8483424 TI - Postmenopausal oestrogen replacement therapy with subcutaneous oestradiol implants. AB - Ten postmenopausal patients were treated by means of subcutaneous oestradiol releasing silastic implants. Half of the patients received 3 implants, each containing 12 mg oestradiol valerate (E2V), while the other half received 4 implants, each containing 27 mg oestradiol benzoate (E2B). Progestogen was added to the treatment for 14 days, 6 weeks after implant insertion and every fourth week thereafter. Serum levels of oestrone (E1), oestradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were followed up. The effects on endometrial thickness, uterine volume and breast tissue were evaluated by ultrasound, mammography also being used for breast examination. The follow-up period was 24 weeks, but the implants were not removed until the climacteric symptoms reappeared. E1 and E2 levels remained higher and gonadotrophin levels lower than the pretreatment values during the 24-week follow-up period. Oestrogen effects were seen in both the uterus and the breasts. Both types of implant were effective in relieving climacteric symptoms. The mean time for symptom return was 10 months (range 6-18 months) in the E2V group and 8 months (range 4-12 months) in the E2B group. Our results indicate that nonbiodegradable controlled-release oestrogen implants offer a safe, effective, convenient and well-accepted alternative means of administering oestrogen replacement therapy. PMID- 8483425 TI - Bone mineral density in surgically postmenopausal women receiving hormonal replacement therapy as assessed by dual photon absorptiometry. AB - A total of 118 postmenopausal women who had undergone hysterectomy and bilateral oophorectomy were invited to participate in this study. Patients were randomly allocated to one of four study groups which received, respectively, conjugated equine oestrogens (CEE) 0.625 mg/day over a 25-day cycle each month (n = 28); transdermal 17 beta-oestradiol 50 micrograms/day over a 24-day cycle each month (n = 28), CEE 0.625 mg/day every day of the month (n = 32) and no treatment the control group (n = 30). All the treated patients also received 2.5 mg/day medroxyprogesterone acetate sequentially for the last 12 days of each cycle. Dual photon absorptiometry was performed before therapy commenced and repeated after 1 year in all four groups. The three therapeutic regimens induced increases in bone mass, whereas a significant decrease was observed in the control group (P < 0.05). PMID- 8483426 TI - Oestrogen and progesterone receptors in the human vagina during the menstrual cycle, pregnancy and postmenopause. AB - Oestrogen receptor (ER) and progesterone receptor (PR) concentrations were measured by enzyme immunoassays in human vaginal tissues. There were no significant differences in either case between the follicular and luteal phases, or in ER concentrations between regularly cycling and postmenopausal women. ER levels were significantly lower in pregnant than in non-pregnant women. PR levels were significantly lower in both postmenopausal and pregnant women than in regularly cycling women. A positive correlation between ER and PR was found in pregnant women and there were correlations between ER and both oestradiol and prolactin in postmenopausal women. This is the first study to compare both ER and PR in the human vagina during the menstrual cycle, pregnancy and postmenopause. PMID- 8483427 TI - Oestradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy. AB - A silicone vaginal ring releasing 5-10 micrograms oestradiol/24 h for a minimum of 90 days has been developed for treatment of urogenital mucosal atrophy. The efficacy, safety and acceptability of the oestradiol-releasing ring were studied in 222 postmenopausal women with symptoms and signs of atrophic vaginal mucosa. The maturation of the vaginal epithelium, as measured by cytological parameters, was significantly improved during treatment. No proliferation of the endometrium was encountered. The therapy had a significant effect on symptoms (vaginal dryness, pruritus vulvae, dyspareunia, urinary urgency) and on signs of atrophic vaginitis, with cure/improvement registered in > or = 90%. The patient acceptability was high, since > or = 90% did not report any discomfort with the ring. Almost all of the sexually active women had the ring in place during coitus and in < or = 2% of cases discomfort was noticed by them or the partner. It is concluded that a vaginal silicone ring giving a continuous release of an ultra low dose of oestradiol is an effective and safe treatment for urogenital oestrogen deficiency. No addition of progestagen is needed. PMID- 8483428 TI - [Arrow poisons--relics of former times?]. PMID- 8483429 TI - [ACE inhibitors for therapy of heart failure]. PMID- 8483430 TI - [Iron deficiency after endurance sports?]. PMID- 8483431 TI - [Is "clinical" better?]. PMID- 8483432 TI - [Calmodulin antagonists]. PMID- 8483433 TI - Dermatology quiz #3. Basal cell carcinoma. PMID- 8483434 TI - Utilization of mammography by Missouri women. PMID- 8483435 TI - Advances in the treatment of calcaneus fracture. AB - The calcaneus is the largest of the tarsal bones and the most commonly fractured, being involved in more than half of all major tarsal injuries. Intraarticular fractures of the calcaneus are seriously disabling and of significant economic consequences. Ninety percent of these injuries occur in working age men, most commonly industrial workers. Many of these workers will never return to their jobs, and of those who do, 20% will be out for up to 3 years. The optimal treatment for intra-articular fractures is controversial. However, in the past few years, progress has been made in understanding the nature of calcaneus fracture. The availability of computed tomographic scanning and improved surgical techniques has improved the outlook for many of these patients to return to productive activity. PMID- 8483436 TI - Transvaginal electron beam cone used in treating an advanced squamous cell carcinoma of the cervix. AB - The transvaginal electron beam cone technique was employed to deliver an additional or "boost" dose to a bulky stage IV-A squamous cell carcinoma of the cervix treated by definitive radiotherapy techniques. The tumor regressed, the patient remaining free of carcinoma until her death due to myocardial infarction more than two years later. PMID- 8483437 TI - Support of collaborative practice. PMID- 8483438 TI - Chemical dependency treatment. PMID- 8483439 TI - Lead poisoning prevention: current clinical practice. PMID- 8483440 TI - Lyme disease--United States, 1991-1992. AB - Surveillance for Lyme disease (LD) was initiated by CDC in 1982 (1), and in 1990, the Council of State and Territorial Epidemiologists (CSTE) approved a resolution making LD nationally reportable. During 1982-1991, states reported 40,195 cases of LD. In 1992, LD accounted for more than 90% of all reported vectorborne illnesses in the United States (CDC, unpublished, 1993). This report summarizes surveillance for LD in the United States during 1991-1992. PMID- 8483441 TI - Physician reporting of Lyme disease--Connecticut, 1991-1992. AB - Although disease reporting by physicians is an essential component of public health surveillance, the extent of physician participation in reporting specific diseases is not routinely assessed. As part of an evaluation of Lyme disease (LD) surveillance, the Connecticut Department of Health Services (CDHS) conducted a study to determine the number and specialty of Connecticut physicians who reported LD cases in 1991 and/or 1992. This report summarizes the results of this study. PMID- 8483442 TI - Commercial fishing fatalities--Alaska, 1991-1992. AB - Based on data from the National Traumatic Occupational Fatality surveillance system, Alaska had the highest state-specific work-related fatality rate during 1980-1989. During this period, the annual average private industry fatality rate in Alaska was 34.8 per 100,000 workers, nearly five times the annual average for the United States (7.0 per 100,000) (1). Fatalities in the commercial fishing industry-which accounts for the second largest percentage of revenue and number of jobs in the state-are among the highest industry-specific rates in the United States (1). Because of the high occupational fatality rates for Alaska, in 1991, CDC's National Institute for Occupational Safety and Health (NIOSH) initiated efforts in Alaska to improve surveillance and describe risk factors for serious occupational injuries associated with the fishing, logging, and air transport industries. This report uses data obtained and analyzed by NIOSH to characterize fishing industry deaths in Alaska for 1991 and 1992. PMID- 8483443 TI - Mandatory bicycle helmet use--Victoria, Australia. AB - On July 1, 1990, the first statewide law in Australia requiring wearing of an approved safety helmet by all bicyclists became effective in Victoria (1989 population: approximately 4.3 million) (Figure 1). Implementation of the law was preceded by a decade-long campaign to promote helmet use among the estimated 2.2 million persons who ride bicycles; the campaign included educational programs; mass media publicity; financial incentives; and efforts by professional, community, and bicycle groups (1,2). This report assesses helmet law enforcement, helmet use, and injuries related to bicycling in Victoria. PMID- 8483444 TI - Tuberculosis morbidity--United States, 1992. PMID- 8483445 TI - Analysis of single protoplasts and regenerated plants by PCR and RAPD technology. AB - We investigated the use of the polymerase chain reaction (PCR) and the associated random amplification of polymorphic DNA (RAPD) technique in the analysis of DNA and specific genes in plant cells at different stages of regeneration in in vitro cultures. We demonstrate that both procedures can be used to differentiate reproducibly between closely related species as well as to reveal levels of DNA polymorphism in regenerated plants. We also demonstrate that both procedures, using protocols that we have developed, are applicable at all tissue culture stages, from single isolated protoplasts to regenerated plants. Possible explanations for the variation levels detected in regenerated wheat plants are advanced. PMID- 8483446 TI - Analysis of regions essential for the function of chromosomal replicator sequences from Yarrowia lipolytica. AB - Two DNA segments exhibiting ARS (autonomously replicating sequence) activity in the dimorphic yeast Yarrowia lipolytica were cloned from its chromosome on an integrative LEU2 plasmid. These ARS segments, designated Y1ARS1 and Y1ARS2, conferred on the hybrid plasmids high transformation efficiency and enabled extrachromosomal transmission of the plasmids in 1 or 2 copies per yeast cell under selective conditions. Deletion analysis showed that at least 728-1003 bp for Y1ARS1 and 1377-1629 bp for Y1ARS2 were required for full function. Both of these regions contained two 10/11 matches to an ARS core consensus in Saccharomyces cerevisiae, whereas neither was similar to the S. cerevisiae centromere sequence. Significantly, both Y1ARS elements contained at, or close to, their boundaries a 13 bp sequence, 5'-TATATTCAAGCAA-3', which resembles the cleavage site for topoisomerase II in Drosophila. A central 524 bp ClaI fragment of Y1ARS2 contained four stretches of a 17 bp direct repeat sequence, 5' GAAAAACAAAAACAGGC-3', and exhibited the electrophoretic behavior typical of bent DNA. PMID- 8483447 TI - SSV1-encoded site-specific recombination system in Sulfolobus shibatae. AB - We present evidence for the existence of a conservative site-specific recombination system in Archaea by demonstrating integrative recombination of Sulfolobus shibatae virus SSV1 DNA with the host chromosome, catalysed by the SSV1-encoded integrase in vitro. The putative int gene of SSV1 was expressed in Escherichia coli yielding a protein of about 39 kDa. This protein alone efficiently recombined linear DNA substrates containing chromosomal (attA) and viral (attP) attachment sites; recombination with either negatively or positively supercoiled SSV1 DNA was less efficient. Intermolecular attA x attA and attP x attP recombination was also promoted by the SSV integrase. The invariant 44 bp "common attachment core" present in all att sites contained sufficient information to allow recombination, whilst the flanking sequences effected the efficiency. These features clearly distinguish the SSV1--encoded site--specific recombination system from others and make it suitable for the study of regulatory mechanisms of SSV1 genome--host chromosome interaction and investigations of the evolution of the recombination machinery. PMID- 8483448 TI - Cotranscriptional expression of mitochondrial genes for subunits of NADH dehydrogenase, nad5, nad4, nad2, in Marchantia polymorpha. AB - Three genes for the subunits of the NADH dehydrogenase (nad5, nad4, and nad2) are tandemly clustered on the liverwort mitochondrial genome. Their gene products showed high levels of amino acid sequence identity with the corresponding subunits from higher plant mitochondria (82.8-84.4%), and significant levels of identity with those from liverwort chloroplast (32.0-33.5%). Podospora anserina mitochondria (21.4-45.9%), and human mitochondria (18.4-27.9%). In addition, these three subunits from liverwort mitochondria have conserved amino acid residues in their central regions. The gene nad5 is interrupted by a 672 bp group I intron, while genes nad4 and nad2 are interrupted by group II introns of 899 bp and 1418 bp, respectively. Northern blot analysis using exon-intron specific probes indicated that these three genes are transcribed as a single precursor mRNA of 9.6 kb in length and are processed into mature mRNA molecules in liverwort mitochondria. Several regions of this nad gene cluster are repeated in the liverwort mitochondrial genome. PMID- 8483449 TI - Molecular structure and genetic regulation of SFA, a gene responsible for resistance to formaldehyde in Saccharomyces cerevisiae, and characterization of its protein product. AB - A 3.7 kb DNA fragment of yeast chromosome IV has been sequenced that contains the SFA gene which, when present on a multi-copy plasmid in Saccharomyces cerevisiae, confers hyper-resistance to formaldehyde. The open reading frame of SFA is 1158 bp in size and encodes a polypeptide of 386 amino acids. The predicted protein shows strong homologies to several mammalian alcohol dehydrogenases and contains a sequence characteristic of binding sites for NAD. Overexpression of the SFA gene leads to enhanced consumption of formaldehyde, which is most probably the reason for the observed hyper-resistance phenotype. In sfa::LEU2 disruption mutants, sensitivity to formaldehyde is correlated with reduced degradation of the chemical. The SFA gene shares an 868 bp divergent promoter with UGX2 a gene of yet unknown function. Promoter deletion studies with a SFA promoter-lacZ gene fusion construct revealed negative interference on expression of SFA by upstream sequences. The upstream region between positions -145 and -172 is totally or partially responsible for control of inducibility of SFA by chemicals such as formaldehyde (FA), ethanol and methyl methanesulphonate. The 41 kDa SFA-encoded protein was purified from a hyper-resistant transformant; it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA. SFA is predicted to code for a long-chain alcohol dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) of the yeast S. cerevisiae. PMID- 8483450 TI - A new yeast gene with a myosin-like heptad repeat structure. AB - We isolated a gene encoding a 218 kDa myosin-like protein from Saccharomyces cerevisiae using a monoclonal antibody directed against human platelet myosin as a probe. The protein sequence encoded by the MLP1 gene (for myosin-like protein) contains extensive stretches of a heptad-repeat pattern suggesting that the protein can form coiled coils typical of myosins. Immunolocalization experiments using affinity-purified antibodies raised against a TrpE-MLP1 fusion protein showed a dot-like structure adjacent to the nucleus in yeast cells bearing the MLP1 gene on a multicopy plasmid. In mouse epithelial cells the yeast anti-MLP1 antibodies stained the nucleus. Mutants bearing disruptions of the MLP1 gene were viable, but more sensitive to ultraviolet light than wild-type strains, suggesting an involvement of MLP1 in DNA repair. The MLP1 gene was mapped to chromosome 11, 25 cM from met1. PMID- 8483451 TI - DNA base sequence changes induced by diethyl sulfate in postmeiotic male germ cells of Drosophila melanogaster. AB - The DNA base sequence changes induced by diethyl sulfate (DES) were analyzed in postmeiotic male germ cells of Drosophila melanogaster. 31 transmissible vermilion mutants were recovered in F1 and F2 generations, with a frequency of 2.6 x 10(-4) for the F1, and of 1.8-13 x 10(-4) for the F2. The results show that DES induces both base pair substitutions (93%) and deletions (7%). In accord with its relatively high ability to alkylate oxygens in DNA, the most frequent type of sequence alteration among the basepair changes are GC-AT transitions, accounting for 73% of mutations, followed by transversions AT-TA (10%). DES also induced AT GC transitions and AT-CG transversions. Both induced deletions were intralocus deletions, not occurring between basepair repeats. No influence of neighboring bases on the mutation position was found. PMID- 8483452 TI - Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae. AB - The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis. PMID- 8483453 TI - Restoration of fertility by antisense RNA in genetically engineered male sterile tobacco plants. AB - Transgenic tobacco plants (Nicotiana tabacum L.) expressing the rolC gene of Agrobacterium rhizogenes under the transcriptional control of the 35S RNA promoter are male sterile. When these plants are genetically crossed with others containing the rolC gene linked in antisense orientation to the 35S RNA promoter, hybrid progeny display restoration of male fertility. Moreover, hybrid progeny are revertant for other features of the rolC phenotype, such as restoration of plant height, leaf pigment content and female fertility. The level of restoration of the characteristics of untransformed tobacco appeared to be independent of the steady-state level of antisense RNA. Addition of six transcriptional enhancer sequences upstream of the 35S transcriptional start region in the antisense construct led to a higher steady-state level of antisense RNA than that produced using a promoter linked to a single enhancer sequence. However no significant difference was observed in the level of attenuation of the rolC phenotype in the progeny of crosses with either one or six transcriptional enhancers linked to the antisense rolC gene. Antisense constructs comprising only 189 bp of the rolC 5' coding region appeared less efficient in attenuating the rolC phenotype than those including the whole rolC coding region as well as its 3' untranslated region. Furthermore, results from experiments on light-controlled rolC gene expression indicate that microsporogenesis is sensitive to rolC gene action during the early stages of flower development. PMID- 8483454 TI - Escherichia coli RuvA and RuvB proteins involved in recombination repair: physical properties and interactions with DNA. AB - Escherichia coli RuvA and RuvB proteins are encoded by an SOS-regulated operon, which is involved in DNA repair and recombination. RuvB has weak ATPase activity, which is enhanced by the addition of RuvA and DNA, and RuvA and RuvB in the presence of ATP promote branch migration at Holliday junctions. In this work, the physical states of RuvA and RuvB and their interactions with DNA were studied by sedimentation analysis and gel filtration chromatography. RuvA formed a stable tetramer in solution, which resisted dissociation by SDS at room temperature. RuvB formed a dimer in solution. When RuvA and RuvB were mixed, an oligomer complex was formed consisting of a tetrameric form of RuvA and a dimeric form of RuvB, and this complex bound to DNA. The maximal enhancement of the RuvB ATPase activity by RuvA was achieved at this stoichiometry in the presence of excess DNA. PMID- 8483455 TI - The Azotobacter vinelandii nifL-like gene: nucleotide sequence analysis and regulation of expression. AB - The nucleotide sequence of the Azotobacter vinelandii nifL-like gene (Av-nifL) was determined. The 1.9 kb sequence shows an open reading frame (ORF) of 1577 bp which encodes a polypeptide of 519 amino acids, with a calculated molecular weight of 57,793. Av-nifL has about 50% homology with the Klebsiella pneumoniae nifL gene (Kp-nifL) at the nucleotide level and a little more than 52% homology at the amino acid level. The N-terminal regions show more homology than the C terminal regions. As is the case in K. pneumoniae, Av-nifL is located just upstream of the A. vinelandii nifA gene (Av-nifA) and both genes constitute an operon. The expression of Av-nifL, however, seems to be independent of NtrA and NtrC. Furthermore, Av-nifL expression is not autogenously regulated by NifA, unlike the case in K. pneumoniae. The expression of an Av-nifL::lacZ fusion in A. vinelandii is inhibited by novobiocin and coumermycin A, which are inhibitors of DNA gyrase. PMID- 8483456 TI - A mutation in the dsbA gene coding for periplasmic disulfide oxidoreductase reduces transcription of the Escherichia coli ompF gene. AB - An insertion mutation in the Escherichia coli dsbA gene, coding for periplasmic disulfide oxidoreductase, dramatically reduces the level of OmpF porin protein in the cell envelope. Studies with chromosomal ompF-lacZ operon and gene fusions indicate that this is due to reduced ompF transcription. Identical effects resulted from growth in medium containing the reducing agent dithiothreitol, but the combined effects of the reducing agent and dsbA were no greater than the effects of each individually. The dsbA mutation did not prevent normal regulation of ompF transcription by the local anaesthetic procaine or by osmolarity. OmpF does not contain a cysteine residue, and the sole cysteine residue in the cytoplasmic membrane regulator of ompF transcription, EnvZ, is predicted to be located on the cytoplasmic side of the membrane, and is therefore unlikely to be involved in the effects of the dsbA mutation. The effects of the dsbA mutation and of the reducing agent on ompF transcription may be due to the failure to from an essential disulfide bond in an as yet unidentified envelope protein that affects ompF transcription. PMID- 8483457 TI - Nucleotide sequence of attP and cos sites of phage CTX and expression of cytotoxin in Pseudomonas aeruginosa PA158. AB - The gene for Pseudomonas aeruginosa cytotoxin (CTX) has been found to be part of a temperate phage with a total size of 35.5 kb. We have investigated several DNA fragments of this phage for CTX production. For phage integration, the phage genome cohesive (cos) ends covalently associate with host DNA of strain PA158. The cos ends and the CTX gene are found on a 3.4 kb EcoRI fragment B and are included in the 11 kb HindIII fragment A and the 8.5 kb BamHI fragment B of the phage DNA. The cos ends are 20 nucleotides long and are located at 338-357 nucleotides upstream of the CTX transcriptional initiation site. The phage attachment (attP) site is also present on the 3.4 kb EcoRI fragment B. The attP site consists of 34 bp and is located at 974-1007 nucleotides upstream of the CTX gene start site. Replication of the vegetative form of the phage is increased at 37 degrees C compared to that at 30 degrees C, while cytotoxin production in infected cells is similar at 30 degrees C and 37 degrees C. It can be concluded, therefore, that the integrated form of the CTX gene is responsible for CTX production. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) showed ten proteins in purified phage preparations; however, CTX could not be detected on Western blots using an enzyme-linked immunofluorescence assay. PMID- 8483458 TI - Toxicity of and mutagenesis by chlorate are independent of nitrate reductase activity in Chlamydomonas reinhardtii. AB - Spontaneous chlorate-resistant (CR) mutants have been isolated from Chlamydomonas reinhardtii wild-type strains. Most of them, 244, were able to grow on nitrate minimal medium, but 23 were not. Genetic and in vivo complementation analyses of this latter group of mutants indicated that they were defective either at the regulatory locus nit-2, or at the nitrate reductase (NR) locus nit-1, or at very closely linked loci. Some of these nit-1 or nit-2 mutants were also defective in pathways not directly related to nitrate assimilation, such as those of amino acids and purines. Chlorate treatment of wild-type cells resulted in both a decrease in cell survival and an increase in mutant cells resistant to a number of different chemicals (chlorate, methylammonium, sulphanilamide, arsenate, and streptomycin). The toxic and mutagenic effects of chlorate in minimal medium were not found when cells were grown either in darkness or in the presence of ammonium, conditions under which nitrate uptake is drastically inhibited. Chlorate was also able to induce reversion of nit- mutants of C. reinhardtii, but failed to produce His+ revertants or Arar mutants in the BA-13 strain of Salmonella typhimurium. In contrast, chlorate treatment induced mutagenesis in strain E1F1 of the phototrophic bacterium Rhodobacter capsulatus. Genetic analyses of nitrate reductase-deficient CR mutants of C. reinhardtii revealed two types of CR, to low (1.5 mM) and high (15 mM) chlorate concentrations. These two traits were recessive in heterozygous diploids and segregated in genetic crosses independently of each other and of the nit-1 and nit-2 loci. Three hcr loci and four lcr loci mediating resistance to high (HC) and low (LC) concentrations of chlorate were identified. Mutations at the nit-2 locus, and deletions of a putative locus for nitrate transport were always epistatic to mutations responsible for resistance to either LC or HC. In both nit+ and nit- chlorate sensitive (CS) strains, nitrate and nitrite gave protection from the toxic effect of chlorate. Our data indicate that in C. reinhardtii chlorate toxicity is primarily dependent on the nitrate transport system and independent of the existence of an active NR enzyme. At least seven loci unrelated to the nitrate assimilation pathway and mediating CR are thought to control indirectly the efficiency of the nitrate transporter for chlorate transport. In addition, chlorate appears to be a mutagen capable of inducing a wide range of mutations unrelated to the nitrate assimilation pathway. PMID- 8483459 TI - Molecular and genetic characterization of SPT4, a gene important for transcription initiation in Saccharomyces cerevisiae. AB - Mutations in the SPT4 gene of Saccharomyces cerevisiae were isolated as suppressors of delta insertion mutations that interfere with adjacent gene transcription. Recent genetic evidence indicates that the SPT4 protein functions with two other proteins, SPT5 and SPT6, in some aspect of transcription initiation. In this work we have characterized the SPT4 gene and we demonstrate that spt4 mutations, like spt5 and spt6 mutations, cause changes in transcription. Using the cloned SPT4 gene, spt4 null mutations were constructed; in contrast to spt5 and spt6 null mutants, which are inviable, spt4 null mutants are viable and have an Spt- phenotype. The DNA sequence of the SPT4 gene predicts a protein product of 102 amino acids that contains four cysteine residues positioned similarly to those of zinc binding proteins. Mutational analysis suggests that at least some of these cysteines are essential for SPT4 function. Genetic mapping showed that SPT4 is a previously unidentified gene that maps to chromosome VII, between ADE6 and CLY8. PMID- 8483460 TI - Telomeric repeat [TTAGGG]n sequences of human chromosomes are conserved in chimpanzee (Pan troglodytes). AB - Using a series of genetic parameters, attempts have been made for more than two decades to establish the close kinship of human (Homo sapiens) with chimpanzee (Pan troglodytes). Molecular and cytogenetic data presently suggest that the two species are closely related. The recent isolation of a human telomeric probe (P5097-B.5) has prompted us to cross hybridize it to chimpanzee chromosomes in order to explore convergence and/or divergence of the telomeric repeat sequences (TTAGGG)n. On hybridization, the human probe bound to both ends (telomeres) of chimpanzee chromosomes, suggesting a concerted evolution of tandemly repeated short simple sequences (TTAGGG)n. Even the terminal heterochromatin of chimpanzee chromosomes was found to be endowed with telomeric repeats, suggesting that evolution of heterochromatin and capping with tandemly repeated short sequences are highly complex phenomena. PMID- 8483461 TI - Characterization of the cyr1-2 UGA mutation in Saccharomyces cerevisiae. AB - cyr1-2 is a temperature-sensitive mutation of the yeast adenylate cyclase structural gene, CYR1. The cyr1-2 mutation has been suggested to be a UGA mutation since a UGA suppressor SUP201 has been isolated as a suppressor of the cyr1-2 mutation. Construction of chimeric genes restricted the region containing the cyr1-2 mutation, and the cyr1-2 UGA mutation was identified at codon 1282, which lies upstream of the region coding for the catalytic domain of adenylate cyclase. Alterations in the region upstream of the cyr1-2 mutation site result in null mutations. The complete open reading frame of the cyr1-2 gene expressed under the control of the GAL1 promoter complemented cyr1-d1 in a galactose dependent manner. These results suggest that at the permissive temperature weak readthrough occurs at the cyr1-2 mutation site to produce low levels of active adenylate cyclase. An endogenous suppressor in yeast cells is assumed to be responsible for this readthrough. PMID- 8483463 TI - [Differential expression of recombinant hybrid proteins containing amino- and carboxy-terminal regions of the exterior large glycoprotein (gp46) of the human T cell leukemia virus (HTLV-I) in Escherichia coli cells]. AB - Plasmid clones capable of expressing a recombinant fusion proteins containing the anthranilate synthase of E. coli (TrpE) and different regions of gp46 HTLV-I were constructed on the basis of pATH-vectors. A high extent of TrpE-gp46 proteolytic degradation took place independently of the bacterial La-protease. Fusion proteins containing an N-terminal part of gp46 were more stable and could be purified in preparative quantities but were less antigenic. On the contrary, a TrpE-gp46 protein encoded by the TaqI-TaqI DNA fragment and containing only 35 C terminal amino acids was still susceptible to degradation but possessed good serologic reactivity. Some of the recombinant proteins obtained can be useful for diagnostics and for preparing monoclonal or polyclonal antibodies. PMID- 8483462 TI - [Expression of the v-src oncogene in Escherichia coli affects the rate of cell growth and leads to phosphorylation of cellular proteins]. AB - The possible influence of expression of v-src oncogene harboring tyrosine specific protein kinase activity on the physiological state of E. coli cells, carrying plasmid which expresses src oncoprotein was studied. The realization of this activity in the cells brings to the phosphorylation of tyrosine in some additional cellular proteins and, as a consequence, to an increased proliferative activity of cells expressing src oncoprotein. PMID- 8483464 TI - [DNAase I hypersensitivity of the 1,5'-flanking region of the tryptophan oxygenase gene in recombinant DNA and chromatin reconstituted with it]. AB - We have examined DNase I hypersensitive sites in the 5'-flanking region of the rat tryptophan oxygenase gene in recombinant plasmids. We have found two DNase I hypersensitive sites in regions that map between -350 to -210 and -180 to -90 bp from the cap site. Both hypersensitive sites are found in supercoiled plasmids but not in linear or relaxed DNA molecules. The position of the hypersensitive sites of the 5'-flanking sequence of the rat tryptophan oxygenase gene in recombinant plasmids correlate with the chromatin sites first determined by Becker et al. The hypersensitive regions in the recombinant plasmids include the DNase I-hypersensitive sites in chromatin but extend somewhat upstream and downstream from these. Computer analysis of the 5'-flanking DNA region of the gene suggests that the DNA fragment spanning nucleotides -231 to -207 forms a potential hairpin loop with 15 unpaired bases. Chromatin reconstitution with histones on supercoiled plasmids carrying the 5'-flanking region of the rat tryptophan oxygenase gene suppresses both in vitro DNase I-hypersensitive sites. We have also shown that the DNA region containing the supercoil-dependent DNase I hypersensitive site in the position between -350 and -210 bp from the cap site may form nucleosomes after reconstitution with histones. PMID- 8483465 TI - [Russian State scientific research program "Human Genome": instrument and method provisions]. PMID- 8483466 TI - [Acyclic analogs of 2',3'-dideoxy-2',3'-didehydronucleoside-5'-triphosphates- terminators of DNA synthesis, catalyzed by a broad set of DNA polymerases]. AB - O-4'-nor-2', 3'-dideoxy-2', 3'-didehydronucleoside 5'-triphosphates are shown to be effective termination substrates of DNA biosynthesis catalyzed by human placental DNA polymerases alpha and epsilon, rat liver DNA polymerase beta, reverse transcriptases of human immunodeficiency virus and avian myeloblastosis virus, and calf thymus terminal deoxynucleotidyl transferase. These compounds do not interact only with the Escherichia coli DNA polymerase I (Klenow fragment). The probable reasons of interaction of acyclo-d4NTP with the DNA synthesizing complexes are discussed. PMID- 8483467 TI - [Affinity modification of 40S ribosomal subparticles from human placenta by derivatives of oligoribonucleotides, containing an AUG codon. Ribosomal proteins, forming a codon-anticodon interaction region]. AB - Using 2',3'-O-[4-N-(2-chloroethyl)-N-methylamino]benzylydene derivatives of AUGUn [32P]pC and 4-[N-(2-chloroethyl)-N-methylamino]benzylmethylphosphoamide derivatives of [32P]pAUGUn, the affinity labelling of human placental 40S ribosomal subunits was studied within 40S initiation complexes obtained in the presence of a ternary complex eIF-2.GTP.Met-tRNA(fMet). Analysis of the ribosomal proteins labelled by these mRNA analogues revealed that proteins S3/S3a, S6, S7, and S14/S15 play a key role in the interaction of the template with the 40S subunit in the presence of the ternary complex eIF-2.GTP.Met-tRNA(fMet). Proteins S2, S4, S5, S8, S9, and S17 are also involved in this interaction. PMID- 8483468 TI - [Genome loses all 5-methylcytosine a life span. How is this connected with accumulation of mutations during aging?]. AB - The 5-methylcytosine (5mC) content in liver DNA has been determined for rats of different age. The rate of the 5mC loss from DNA is maximal in pre- and neonatal rats, 1.28% of reduction of the 5mC content per day, then it decreases to 0.33% and becomes minimal and constant in adult rats, 0.028% per day. During pregnancy and the first 15 days of postnatal development rat genome loses 49% of all 5mC. Within the next 45 days 15% of 5mC disappears, and during maximal rat life span, about four years, 39% of the genomic 5mC may be lost. Thus, it has been found for the first time that the animal genome loses practically all 5mC residues during the life span. Analysis of the literature data shows that for embryos the rate of the 5mC loss from DNA proves to be higher than that for adult animals by 96 times for mice, 69-for rats and 28-for cows. The rate of embryonal DNA hypomethylation may be inversely proportional to the pregnancy duration of species. In adult animals the rate inversely correlates with their maximal life span and accounts for the 5mC loss from DNA of a mouse by 0.028%, of a rat by 0.024%, of a hamster by 0.007%, of a cow by 0.004% and of a human being by 0.0005% per day. During the entire ontogenesis, the genome of a mouse loses 93% of all 5mC residues, that of a rat-101% and of a cow-88%. The age-dependent loss of 5mC from DNA is also typical for cell lines aging in vitro. It is constant, as a rule, and correlates with the number of cell population doublings (PD). The removal of all 5mC from DNA corresponds to 70-130 PD for human, 40-60 PD-for hamster and 6 PD- for mouse cells. In immortal lines the level of DNA methylation is stable or grows with age. A possible mechanism of an age-related 5mC loss from DNA is discussed. DNA hypomethylation may result from 5mC deamination directly at the moment of replicative DNA methylation and subsequent reparation of the G.T mispairs which leads to accumulation of the 5mC-->T+C substitutions in the genome with each cell division. So DNA methylation may serve as an ideal mechanism for counting cell divisions in vivo and in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8483469 TI - [Synthesis of nucleoside analogs containing a cis-2-pentene fragment and their triphosphates]. AB - Acyclic analogs of thymidine, adenine, and cytosine where the ribose moiety is replaced with cis-5-hydroxypenthene, were obtained via condensation of cis-5 acetoxy-1-bromo-2-pentene with nucleic acid bases. Triphosphate derivatives of the new nucleosides were also synthesized to evaluate their action as terminators of DNA synthesis catalyzed by DNA polymerases. PMID- 8483470 TI - [Cloning the region of chromosome 22 participating in translocation t(9,22) in human chronic myeloid leukemia]. AB - Using oligonucleotide probes, sequences containing the Mbcr locus involved in chromosome translocation t(9:22) were cloned form the library of human genes in the Charon 4A vector. The recombinant clone lambda BCR 1.1 obtained contained Mbcr sequences, but the 3' region of the Mbcr locus in lambda BCR 1.1 clone was strongly altered. Subcloning of a fragment of the altered region and blot hybridization analysis using it as a DNA probe revealed recombination in the 3' region of the Mbcr locus in clone lambda BCR 1.1 which resulted in insertion of unknown sequences into the region. A modified system is suggested for chromosome 22 breakpoint identification using restriction analysis of genome DNA with four restriction endonucleases and one 5'-DNA probe. PMID- 8483471 TI - [Pathological cleavage of human immunodeficiency virus gp160 protein in infected cells as a probable factor for infection becoming chronic]. AB - The synthesis of HIV-1 (IIIb isolate) structural protein in chronically (CI) and acutely infected (AI) MT4 cells was studied. During long-term cultivation the CI system was characterized by high involvement of the cells into infection (up to 100%), high level of virus-specific protein synthesis, moderate virus yield, but absence of any virus-induced cytopathic effects and normal growth potential of infected cells. AI cells demonstrated a similar level of synthesis of virus specific proteins, higher virus yield, and rapid progression of cytopathicity followed by total cell death. Most of the HIV gp160 protein molecules undergo rapid cleavage in the region between the point of conventional cleavage and the transmembrane domain, being removed from the physiologically competent pool, but a small portion of gp160s undergo apparently normal intracellular development. According to our data, the two HIV variants (normal and defective) persist in CI system and pathological cleavage of defective virus gp160 protein results most probably in chronization of infection. PMID- 8483473 TI - [Genomic DNA as compact particles: morphology, biochemical analysis and optical properties]. AB - Compact DNA particles have been obtained by a new method we developed to isolate high-molecular-weight DNA. The method includes exhaustive proteolysis while the cellular DNA is folded in compact state in polyethylene glycol-containing aqueous salt media. The DNA particles derived from interphase nuclei have a diameter of 8 10 microns and each of them contains the genome of an individual cell. The DNA particles derived from isolated metaphase chromosomes present tightly packed DNA of individual chromosomes. The compact particles contain no proteins detectable by electrophoretic analysis and so appear to be formed by DNA only. These data have been confirmed by electron microscopy, when the particles investigated with the protein monolayer technique have revealed only spread DNA molecules. Simultaneously the microscopic observations of DNA particles of different origin and of their behaviour in the absence of compactizing agents support the idea that during formation of compact particles the intrinsic features of DNA folding in nuclei and chromosomes have been conserved. PMID- 8483472 TI - [Study of the effect of the cDNA for the human apolipoprotein A-I gene in transgenic rabbits: modeling the neurological syndrome of human Tangier disease]. AB - Two transgenic rabbits which carried human apolipoprotein A-1 (apo A-1) cDNA under mouse ribosomal protein L/32 promoter were obtained. The effectiveness of transgenosis was confirmed by DNA dot/blot and Southern blot hybridizations. Both transgenic animals had paralyses of fore or fore and high limbs. Electron microscopy demonstrated distinct degradative changes of those parts of spinal cord which were responsible for leg skeletal muscle innervation. RNA dot/blot hybridization showed transgene expression in liver and brain but not in kidney of adult transgenic animal. However, analysis of blood serum lipids and immunochemical determinations gave no indications of the presence of human apo A 1 in adult transgenic rabbit. The data obtained allow us to suggest that the observed pathology was due to interference of native and foreign protein products of apo A-1 gene expression in CNS in the course of embryo development. This suggestion was supported by results of in situ hybridization of 5- and 9-week human embryo sections with apo A-1 cDNA, showing effective expression of apo A-1 gene in neural cells of CNS. Results of transgenosis may be viewed as modeling of the neurological syndrome of human Tangier disease. PMID- 8483474 TI - [HIV-1 p17 matrix protein is transported into the cell nucleus and binds with genomic viral RNA]. AB - We have shown that gag polyprotein p55 is cleaved in cytosol rapidly after its synthesis, during 2 h, and p17 enters the nuclei while p24 resides in cytosol. To determine whether the nascent p17 is associated with viral genomic RNA in the nuclei, the cells were fractionated, the viral complexes were immunoprecipitated by monoclonal antibodies against gag proteins, and RNA was extracted and analyzed by slot and blot hybridization. Monoclonal antibodies against p17 precipitated all the viral RNA from the nuclei including full-size genomic RNA and essential part from membranes while monoclonal antibodies against p24 did not precipitate any viral RNA from the nuclei. These data suggest that matrix protein is linked to genomic RNA in the nuclei and rise the possibility that p17 may transfer viral nucleocapsids from the nuclei to plasma membranes, the site of virus assembly. PMID- 8483475 TI - [Effective expression of genes for interleukin-2 and its mutant analogs in E. coli cells]. AB - Recombinant plasmids were constructed for the efficient expression in E. coli cells of the human interleukin-2 (HIL-2) gene and two its mutant analogues obtained by of chemical-enzymic synthesis and polymerase chain reaction (deletion of 14 C-terminal amino acids and a change of the codon for Trp121 to Phe). The recombinant HIL-2 but not the mutant analogues were shown to be biologically active. Both analogues obtained were weak antagonists to HIL-2. PMID- 8483476 TI - [Study of the form of bacteriophage T7 RNA polymerase containing point substitutions in the region of functionally important amino acid residues]. AB - A study was carried out on the influence of point mutations of the functional amino acid residues on the secondary and ternary structure of bacteriophage T7 RNA polymerase as well as on the activity of the enzyme. A change in residue 631 is accompanied by significant changes in secondary structure (alpha-->beta transition). The substitution Lys-172 Leu changes both the secondary and ternary structures whereas the deletion of residues 172-173 does not lead to such changes. Changes in residues 631-632 do not affect the ability of the enzyme to bind the promoter and/or the synthesis of a full-length transcript but disturbs phosphodiester bond formation. PMID- 8483477 TI - Human estrogen receptor bound to an estrogen response element bends DNA. AB - We have used gel mobility shift assays to examine changes in DNA bending induced by binding of human estrogen receptor (hER) to a series of estrogen response element (ERE) containing DNA fragments. Competition experiments with ERE containing DNA fragments and antibody supershift experiments demonstrated that ER in crude extracts from MCF-7 human breast cancer cells exhibited specific interaction with the ERE. Using DNA bending standards, we found that binding of ER to a single ERE induced a reproducible DNA bend of 56 degrees. This was 1.65 fold greater than the 34 degrees bending angle we recently reported for binding of bacterially expressed ER DNA binding domain. The DNA bending angle induced was the same whether the salt-extracted receptor was unoccupied, occupied by 17 beta estradiol, or occupied by trans-hydroxytamoxifen. To determine if proteins associated with ER in MCF-7 cells affect the degree of bending, we examined the ability of partially purified hER expressed in yeast to bend DNA. The degree of bending induced by the partially purified yeast ER was the same as the bending induced by crude MCF-7 cell ER. More highly purified ER from yeast extracts did not bind to an ERE-containing DNA fragment, suggesting that additional proteins may play an important role in the interaction of the ER with the ERE. When two EREs were present in the DNA fragment, a small but reproducible increase in bending was observed. Our demonstration that binding of hER to the ERE induces DNA bending suggests a possible role for DNA bending in ER-induced transcription activation. PMID- 8483478 TI - Nerve growth factor induces transcription of NGFIA through complex regulatory elements that are also sensitive to serum and phorbol 12-myristate 13-acetate. AB - The expression of NGFIA (also known as egr1, zif268, TIS8, krox24, and d2) is rapidly and transiently increased by nerve growth factor (NGF) in PC12 cells. The 5'-region of this gene includes four serum response elements (SREs), a cAMP-like response element, an AP1-like response element, and an SP1-binding site. From deletion analysis of chloramphenicol acetyltransferase reporter constructs, we have established that the first 106 basepairs 5' of the transcriptional start site are sufficient for induction of NGFIA by NGF in PC12 cells; deletion beyond this point results in dramatically reduced induction of the gene. Using defined mutations in the NGFIA promoter and NGFIA-thymidine kinase hybrid promoters, we have defined three elements (SRE1, SRE2, and AP1-like) in the first 106 basepairs of upstream DNA, each of which contributes to induction of NGFIA by NGF. Cooperation by two of these elements (i.e. the two SREs or one SRE and the AP1 like element) is sufficient to confer transcriptional induction by NGF, but the combination of all three elements increased induction by NGF more effectively than a pair of elements. This suggests that the response of NGFIA to NGF is mediated by a cis-acting sequence that is composed of at least three distinct elements. An oligonucleotide composed of SRE1 and SRE2 that can confer the ability for NGF induction to heterologous promoter constructs complexes with proteins in PC12 cell nuclear extracts, but the protein-DNA complexes do not appear to be altered by NGF treatment, as measured by DNA mobility shift assays. We have also established that the regulatory region of NGFIA that mediates NGF induction also mediates the induction by serum and phorbol 12-myristate 13 acetate, suggesting that multiple signal transduction pathways must converge on these sequences to regulate the expression of this gene. PMID- 8483479 TI - Parathyroid hormone represses alpha 1(I) collagen promoter activity in cultured calvariae from neonatal transgenic mice. AB - We examined the effect of PTH on the activity of alpha 1(I) collagen promoter fusion genes in cultured calvariae from transgenic mice. The parent construct, ColCAT 3.6, contains 3520 basepairs of 5' rat alpha 1(I) collagen DNA, 115 basepairs of untranslated alpha 1(I) collagen-coding DNA, and the bacterial chloramphenicol acetyltransferase reporter gene, while the 5'-deletion ColCAT 2.3 contains 2296 kilobases of rat alpha 1(I) collagen promoter sequence. Transgenic mouse lines harboring these collagen promoter fusion genes were developed using the oocyte microinjection technique, and for each construct, three different lines of mice were tested. Calvariae from 6- to 8-day-old transgenic mice were cultured for 48 h with or without bovine PTH-(1-34). ColCAT 3.6 and ColCAT 2.3 were expressed at comparable levels in calvariae and were inhibited by PTH. There were parallel decreases in the incorporation of [3H]proline into collagen and levels of the endogenous alpha 1(I) collagen mRNA and transgene mRNA. Forskolin at 10 microM mimicked the inhibitory effect of PTH on promoter activity in ColCAT 3.6 and ColCAT 2.3 calvariae. A RNase protection assay showed that the transgene was initiated correctly from the transgene promoter. These data show that PTH and cAMP can repress collagen promoter activity in calvariae from transgenic mice, suggesting that the alpha 1(I) collagen promoter may contain cis elements down stream of -2.3 kilobases that mediate PTH and cAMP repression of collagen gene expression in bone. Cultured bone explants from transgenic mice can be used as a model to study hormonal regulation of alpha 1(I) collagen promoter constructs. PMID- 8483480 TI - Follicle-stimulating hormone increases the turnover of G-protein alpha i-1- and alpha i-2-subunit messenger RNA in Sertoli cells by a mechanism that is independent of protein synthesis. AB - We have shown previously that FSH differentially regulated G-protein alpha i subunit mRNA levels in primary cultures of rat Sertoli cells. The mechanism by which FSH regulated the steady state levels of these mRNAs was investigated by assessing the effect of FSH on G-protein alpha-subunit mRNA stability and the potential involvement of newly synthesized proteins. The half-life (t 1/2) of alpha-subunit mRNA was determined by inhibiting Sertoli cell transcription with actinomycin-D and quantifying alpha-subunit mRNA levels by Northern blot analyses. Transcripts for alpha i-2 and alpha 3 were extremely stable, possessing t1/2 of 44 and 51 h, respectively. In contrast, the t1/2 of alpha i-3 mRNA was only 3.6 h. Turnover of alpha i-1 mRNA occurred as a two-phase decay, with an initial t1/2, fast of 0.8 h, followed by a second phase with t1/2, slow of 11.1 h. Treatment of Sertoli cells with FSH in the presence of actinomycin-D destabilized the alpha i-1 mRNA to a single phase decay with a t1/2 of 5.7 h. FSH also decreased the stability of the alpha i-2 mRNA from a t1/2 of 51 h to a t1/2, fast of 16.5 h. These effects of FSH on alpha i-1 and alpha i-2 mRNA stability may contribute to the ability of FSH to decrease steady state alpha i-1 and alpha i-2 mRNA levels. The effect of FSH on alpha i-3 mRNA stability was not significant, suggesting an alternative mechanism regulating the FSH-mediated increase of alpha i-3 mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483481 TI - The human osteocalcin promoter directs bone-specific vitamin D-regulatable gene expression in transgenic mice. AB - Osteocalcin is a major noncollagenous protein of bone regulated by 1,25 dihydroxyvitamin D3 [1,25-(OH)2D3] and is believed to be expressed only by differentiated osteoblasts. We introduced a 3.9-kilobase human osteocalcin gene promoter (hOCP)-chloramphenicol acetyltransferase (CAT) fusion gene into the germ line of mice. Examination of tissue extracts from these transgenic mice demonstrated that the expression of CAT was restricted to bone-associated tissues and the brain. Immunohistochemical staining of femur tissue sections using CAT antibodies localized the production of CAT protein to osteoblasts and maturing chondrocytes. Previous studies via transient transfection into osteoblast-like cells have identified a vitamin D response element approximately 500 basepairs up stream of the hOCP capable of mediating 1,25-(OH)2D3 induction. As a consequence, regulation of the transgene was examined in homozygous transgenic lines for sensitivity to 1,25-(OH)2D3. Hormonal deficiency was created using a low calcium diet supplemented with 0.8% SrCl2 for 7 days and was restored in experimental mice by injection of 25 ng 1,25-(OH)2D3/day, ip, for 3 days. The low vitamin D3 diet decreased CAT activity several-fold in extracts from calvaria, femur, and brain compared to that in mice maintained on a normal diet, while 1,25-(OH)2D3 supplementation restored and enhanced CAT activity over control values. These data demonstrate that hOCP is sufficient to direct osteoblast-specific 1,25 (OH)2D3-sensitive gene expression in mice in addition to the unexpected regulatable expression in brain tissue. PMID- 8483482 TI - NCLEX is changing. PMID- 8483483 TI - A very special vacation. PMID- 8483484 TI - Congress agrees to new NIH office for AIDS programmes. PMID- 8483486 TI - Hughes institute displays new home. PMID- 8483485 TI - Britain's Wellcome Trust stretches its financial wings. PMID- 8483487 TI - Congress wrestles with electronic highway bill. PMID- 8483488 TI - NIH task force to examine 'culture' of discrimination. PMID- 8483489 TI - FDA panel sees problems with labelling of milk hormone. PMID- 8483490 TI - Keeping warm. PMID- 8483491 TI - Not exclusive. PMID- 8483492 TI - Has Duesberg a right of reply? PMID- 8483493 TI - DNA repair. Engagement with transcription. PMID- 8483494 TI - T cells. Immunological agnosia. PMID- 8483495 TI - Aluminium--Alzheimer's link? PMID- 8483496 TI - Illusion and view stability. PMID- 8483497 TI - C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation. AB - Vulval differentiation in Caenorhabditis elegans is controlled by intercellular signalling mediated by a receptor tyrosine kinase and a ras gene product. The lin 45 gene encodes a homologue of the raf family of serine/threonine kinases and is necessary for vulval differentiation. The lin-45 raf gene product appears to act downstream of the ras protein in this pathway. A proto-oncogene-mediated signalling pathway may be a common feature of metazoan development. PMID- 8483498 TI - Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen presenting cells. AB - Activation of CD4+ T helper cells results from the occupancy of the T-cell receptor (TCR) by immunogenic peptide bound to a class II major histocompatibility complex (MHC) molecule, together with a co-stimulatory signal from the antigen-presenting cell (APC). This activation leads to proliferation, cytokine production (Th1 or Th2 profile) and cytolysis. Engagement of the TCR in the absence of co-stimulation causes Th1 cells to become unresponsive to subsequent antigenic stimulation. We have previously demonstrated that analogues of an immunogenic peptide could stimulate Th1 and Th2 cells to carry out some effector functions without inducing proliferation, a phenomenon we term partial activation. Here we study the consequences of such partial activation through the TCR of two Th1 clones using peptide analogues presented by a live APC. A peptide analogue that is unable to stimulate clonal proliferation or production of cytokine or inositol phosphate can induce the T cells to become profoundly unresponsive to subsequent stimulation with the immunogenic peptide. Thus, altering the ligand of the TCR by using a peptide analogue on a functional APC sends a signal to Th1 clones that results in anergy. PMID- 8483499 TI - Regulation of Langerhans cell function by nerves containing calcitonin gene related peptide. AB - Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function. PMID- 8483500 TI - Continuous c-fos expression precedes programmed cell death in vivo. AB - The development of a multicellular organism involves a delicate balance among the processes of proliferation, differentiation and death. Naturally occurring cell death aids tissue remodelling, eliminates supernumerary cell populations and provides structural elements such as hair and skin. In the nervous system, selective cell death contributes to the formation and organization of the spinal cord and sympathetic ganglia, retina and corpus callosum. But cell death also occurs in several neuropathological conditions, such as amyelotrophic lateral sclerosis and Alzheimer's disease. Therefore an elucidation of the mechanisms responsible for cell death is critical for an appreciation of both normal development and neuropathological disorders. Using a fos-lacZ transgenic mouse, we provide evidence showing that the continuous expression of Fos, beginning hours or days before the morphological demise of the cell, appears to be a hallmark of terminal differentiation and a harbinger of death. PMID- 8483501 TI - p70s6k function is essential for G1 progression. AB - An essential step in the pathway by which growth factors trigger cellular proliferation is the induction of high levels of protein synthesis. This appears in part to be controlled by multiple phosphorylation of the ribosomal protein S6 (refs 4, 5). The main kinase responsible, p70s6k (refs 6-8), is activated through the phosphorylation of four sites clustered in a putative autoinhibitory domain, which is mediated by a signalling pathway distinct from those used by other well characterized mitogen-activated serine/threonine kinases (such as p42/p44mapk or p90rsk; refs 10, 11). Here we investigate the role of p70s6k in the mitogenic response. Microinjection of quiescent rat embryo fibroblasts with any of three distinct polyclonal antibodies to p70s6k abolishes serum-induced entry into S phase of the cell cycle. This effect is preceded by almost complete abrogation of the activation of protein synthesis and the expression of an essential immediate early gene product, c-fos. The inhibitory effect on DNA synthesis is also elicited by microinjection of the antibodies late in G1 phase, consistent with the finding that p70s6k activity remains high throughout G1. PMID- 8483502 TI - A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5. AB - Interleukin-5 (IL-5) is a lineage-specific cytokine for eosinophilpoiesis and plays an important part in diseases associated with increased eosinophils, such as asthma. Human IL-5 is a disulphide-linked homodimer with 115 amino-acid residues in each chain. The crystal structure at 2.4 A resolution reveals a novel two-domain structure, with each domain showing a striking similarity to the cytokine fold found in granulocyte macrophage and macrophage colony-stimulating factors, IL-2 (ref. 5), IL-4 (ref. 6), and human and porcine growth hormones. IL 5 is unique in that each domain requires the participation of two chains. The IL 5 structure consists of two left-handed bundles of four helices laid end to end and two short beta-sheets on opposite sides of the molecule. Surprisingly, the C terminal strand and helix of one chain complete a bundle of four helices and a beta-sheet with the N-terminal three helices and one strand of the other chain. The structure of IL-5 provides a molecular basis for the design of antagonists and agonists that would delineate receptor recognition determinants critical in signal transduction. This structure determination extends the family of the cytokine bundle of four helices and emphasizes its fundamental significance and versatility in recognizing its receptor. PMID- 8483503 TI - The dTAFII80 subunit of Drosophila TFIID contains beta-transducin repeats. AB - A key component of the RNA polymerase II transcriptional apparatus, TFIID, is a multi-protein complex containing the TATA box-binding protein (TBP) and at least seven tightly associated factors (TAFs). Although the functions of most TFIID subunits are unknown, it is clear that TAFs are not necessary for basal activity but that one or more are required for regulated transcription, and so behave as coactivators. The presence of multiple subunits indicates that there is an intricate assembly process and that TAFs may be responsible for other activities. We have described the properties of the subunit dTAFII110, which can interact directly with the transcriptional activator Sp1 (ref. 5). In addition, the largest subunit, dTAFII250, binds directly to TBP and links other TAFs to the complex. Here we describe the cloning, expression and partial characterization of the Drosophila TAF of M(r) 80,000, dTAFII80. Sequence analysis reveals that dTAFII80 contains several copies of the WD40 (beta-transducin) repeat. Moreover, dTAFII80 shares extended sequence similarity with an Arabidopsis gene, COP1, which encodes a putative transcription factor that is though to regulate development. We have expressed recombinant dTAFII80 and begun to characterize its interaction with other members of the TFIID complex. Purified recombinant dTAFII80 is unable to bind TBP directly or to interact strongly with the C terminal domain of dTAFII250 (delta N250). Instead, dTAFII80 is only able to recognize and interact with a higher-order complex containing TBP, delta N250, 110 and 60. These findings suggest the formation of TFIID may require an ordered assembly of the TAFs, some of which bind directly to TBP and others that are tethered to the complex as a result of specific TAF/TAF interactions. PMID- 8483504 TI - Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2. AB - Defects in human DNA repair proteins can give rise to the autosomal recessive disorders xeroderma pigmentosum (XP) and Cockayne's syndrome (CS), sometimes even together. Seven XP and three CS complementation groups have been identified that are thought to be due to mutations in genes from the nucleotide excision repair pathway. Here we isolate frog and human complementary DNAs that encode proteins resembling RAD2, a protein involved in this pathway in yeast. Alignment of these three polypeptides, together with two other RAD2 related proteins, reveals that their conserved sequences are largely confined to two regions. Expression of the human cDNA in vivo restores to normal the sensitivity to ultraviolet light and unscheduled DNA synthesis of lymphoblastoid cells from XP group G, but not CS group A. The XP-G correcting protein XPGC is generated from a messenger RNA of approximately 4 kilobases that is present in normal amounts in the XP-G cell line. PMID- 8483505 TI - Identical defects in DNA repair in xeroderma pigmentosum group G and rodent ERCC group 5. AB - Humans with the complementation group G form of the inherited syndrome xeroderma pigmentosum (XP) are hypersensitive to solar ultraviolet light because of a defect in nucleotide-excision repair of DNA. Some individuals are also affected with Cockayne's syndrome, and have neurological abnormalities. Here we report that the DNA repair deficiency of XP-G cell extracts can be corrected by addition of protein fractions from normal cells. Repair proficiency can also be restored by mixing XP-G cell extracts with extracts from different repair-defective cell lines, with one exception. Extracts from cells representing group 5 of a set of ultraviolet-sensitive rodent mutants fail to complement XP-G extracts. XP-G and group 5 correcting activities co-elute after approximately 1,000-fold purification from HeLa cells. An antibody directed against a recombinant fragment of the XP-G complementing protein (XPGC) inhibits excision repair by normal cell extracts, and activity can be restored with an XP-G/group 5 complementing fraction. These data strongly suggest that the XPGC and group 5 correcting (ERCC5) proteins are identical. PMID- 8483506 TI - Clonogenic cytotoxicity testing by microdrop encapsulation. AB - Cytotoxicity is defined as the in situ measurement of cellular function in response to a toxic substance. Cytotoxicity assays are widely used in drug screening and development research to minimize the number of compounds on which expensive mammalian animal model toxicology studies are performed. PMID- 8483507 TI - NIH: a strategy for the 21st century? PMID- 8483508 TI - Peracute surgery of aneurysms with intracerebral hematomas. AB - Out of a series of 252 patients who underwent aneurysm surgery, 19 (7.5%) were operated on in a "peracute stage" in the poor grades Hunt & Hess IV (n = 11), IV V (n = 2), and V (n = 6). All patients suffered from large aneurysmal intracerebral hematomas which were evacuated after decompressive craniotomies, all aneurysms (ACA: n = 1, ACoA: n = 4, MCA: n = 12, ICA: n = 2) could be clipped. 4 patients died within the first 3 postoperative days, 6 patients reached a poor result remaining in an apallic syndrome or a state of high invalidity, 8 obtained a fair result with personal autonomity, and 1 patient recovered completely. Although this kind of aneurysm bleeding is combined with high mortality and morbidity, we nevertheless emphasize its surgical treatment as soon as possible because of the lack of other efficient therapeutical procedures. PMID- 8483509 TI - Classification of frontal fossa fractures associated with cerebrospinal fluid rhinorrhea, pneumocephalus or meningitis. Indications and time for surgical treatment. AB - The classification of anterior fossa fractures with their sequelae: cerebrospinal fluid (CSF) rhinorrhea, pneumocephalus, or meningitis is presented. This classification is based on five selection criteria which are discussed in this paper. This classification resulted in the table of indications for operative treatment, according to which the appropriate time for operation in urgent cases is immediately, in cases with absolute indication 5 to 6 days after the injury, in long-lasting CSF rhinorrhea or pneumocephalus 10 days after the onset, in intermittent or delayed rhinorrhea and/or pneumocephalus as soon as these signs occur, and in cases of meningitis soon after recovery. This study is based on the analysis of 52 consecutive surgically treated cases, collected from 1984 up to December 1989. PMID- 8483510 TI - [Whiplash trauma of the cervical spine from the neurosurgical, traumatologic and psychologic viewpoint]. AB - Since the early 50's, whiplash injury has been a subject of intensive study in order to find out the genesis of this disease. Unfortunately, most of the studies were planned retrospectively and were based on inhomogeneous groups of patients. In our prospective study, we tried to keep the patient group homogeneous. 62 patients were examined neurologically and radiologically immediately after the accident. Furthermore, they underwent a psychological test, the so-called Freiburg personality profile. 6 months later the patients were checked again. On the basis on our findings, the suspected psychological influence has to be confirmed. Preexisting degenerative lesions of the cervical spine, also, are undoubtedly prognostic for longer-lasting symptoms. PMID- 8483511 TI - [Value of neuroradiologic procedures in preoperative assessment of cervical myelopathy]. AB - The diagnostic value of computed tomography (CT), myelography, myelo-CT and magnetic resonance imaging (MRI) was retrospectively investigated in 94 patients in whom Cloward's operation had been performed due to symptoms of cervical myelopathy (CM). In 55 patients with "classical" cervical spondylotic myelopathy all investigated diagnostic procedures demonstrated a comparably high degree of sensitivity and specificity, thus proving comparable for diagnosing pathological alterations of the cervical spine. In 39 patients with CM as a consequence of an acute cervical disk prolapse, however, MRI was superior and offered the highest diagnostic accuracy. The following general diagnostic strategy in patients with CM can be suggested: Conventional plain film radiography of the cervical spine, axial CT of the involved segments and MRI of the cervical spine in sagittal and transversal orientation, using T1 and T2 weighted pulse sequences. The combined use of these techniques allows the exact evaluation of any relevant structure alterations of the cervical spine that determine differential therapeutic approaches. PMID- 8483512 TI - Spinal extradural angiolipoma: case report and literature review. AB - A case report of a 12-year-old child with a spinal extradural angiolipoma is presented. The tumor was totally removed and a good recovery was obtained. In a review of 43 previous cases, the clinical, radiological, and histological features of the tumor are discussed. It is stressed that spinal angiolipomas and spinal lipomas have to be considered as two different clinicopathological entities in order to ensure adequate treatment and prognosis. PMID- 8483513 TI - Ventral brain stem schwannoma at the entry zone of the hypoglossal nerve. AB - The unusual case of a ventral brain stem schwannoma located at the entry zone of the hypoglossal nerve in a 49-year-old woman is reported. The diagnosis of a schwannoma was confirmed histologically after partial tumor resection via the dorsolateral, suboccipital, transcondylar approach. Hypotheses for the pathogenesis of intramedullary schwannomas are discussed. PMID- 8483514 TI - Middle cerebral artery aneurysm developing apparently de novo. AB - The author reports a patient with a fatal subarachnoid and intracerebral hemorrhage from a middle cerebral artery aneurysm, which apparently developed de novo. 18 years before, the patient was operated for an anterior communicating artery aneurysm and, during this procedure, an anterior cerebral artery was ligated. Hemodynamic disturbances due to anterior artery occlusion are suggested as the cause of new aneurysm formation. PMID- 8483516 TI - Surgical treatment and results in patients suffering from lumbar spinal stenoses. AB - Stenosis of the lumbar spinal canal is contributing to 3-5% of all patients operated on a lumbar nerve root compression syndrome. Morphologically, a reduction of the midsagittal diameter of the spinal canal to less than 12 mm or stenoses of the lateral recessus or foramen intervertebrale have been described. In our department 37 patients with a lumbar spinal stenosis have been surgically treated between 1982 and 1987. Spinal stenosis is a disease of aged patients mostly suffering for a long history. The main symptoms are lumbar and sciatic pains, neurological deficits and a claudicatio intermittens spinalis. Neuroradiologically, the diagnosis can be confirmed by CT, myelography or MRI. These studies were demonstrating the stenosis in 69% at the level of L4/5, multiple stenoses have been found in 22% of all cases. An additional disc herniation existed in 35% of the patients. Concerning the specific complaints of the patients and their neuroradiological findings, the extent of the surgical decompression was decided on individually in each patient. We performed 22 laminectomies, 11 hemilaminectomies, in 3 cases an extended flavectomy and in one case an implantation of a dorsal column stimulation device. The postoperative follow-up period, ranging from 3 months to 3 years, demonstrated a complete recovery in 53%, a marked reduction of complaints in 44% of all cases. One patient did not respond to surgical treatment, but in the remaining cases surgical treatment led to satisfactory results. PMID- 8483515 TI - Outcome of patients with aneurysmal and presumed aneurysmal bleeding. A hospital study based on 100 consecutive cases in a neurological clinic. AB - One hundred patients with spontaneous subarachnoid hemorrhage due to aneurysm or presumed aneurysm consecutively admitted to a neurological clinic and subjected to CCT during the first 72 hours were examined retrospectively. The outcome after two months as defined by the Glasgow Outcome Scale (GOS) was relatively good: 23% of the patients suffered management mortality (GOS I) (postoperative lethality 8%), 3% showed GOS-Grade II, 14% grade III, 17% grade IV, and 43% grade V. The extent of intracranial hemorrhage correlated well with the initial Hunt-Hess Grade which, in turn, had a strong influence on case fatality and the degree of disability. Lethal factors were: 1. massive subarachnoid hemorrhage together with a massive ventricular hemorrhage (p < 0.001), 2. massive subarachnoid hemorrhage together with an intracerebral hematoma > 20 ml (p < 0.05). Case fatality was lower when angiography was negative. In our study rebleeding (12%) and delayed cerebral ischemia (DCI) (18%) were less frequent and the lethality due to acute hydrocephalus (5%) and delayed cerebral ischemia (5%) was less pronounced than in comparable studies. The degree of disability (GOS) was directly related to the amount of intracranial blood, to the development of acute or chronic hydrocephalus, delayed cerebral ischemia and rebleeding. DCI occurred in 60% of patients with marked hydrocephalus. Rebleeding was more frequent in patients with acute hydrocephalus. Hydrocephalus, DCI, and rebleeding were associated with a poorer initial grade on the Hunt and Hess Scale. PMID- 8483517 TI - Concentrations of albendazole in serum, cerebrospinal fluid and hydatidous brain cyst. AB - A young girl with cerebral echinococcosis was treated with albendazole (13 mg/kg/d, p.o.). The concentrations of albendazole sulphoxide were determined in serum, cerebrospinal fluid and hydatidous cyst over a month. The mean ratios of concentration were: CSF/serum = 50%, cyst/serum = 40%, cyst/CSF = 80%. PMID- 8483518 TI - Somato-sensory evoked potentials in root lesions and stenosis of the spinal canal (their diagnostic significance in clinical decision making). AB - The aim of the present study was to determine the significance of different SEP techniques and parameters in clinical evaluation of cases of lumbar and cervical root lesions and stenosis of the spinal canal. Using a qualitative rating scale, 92 cases were analyzed retrospectively whose primary diagnosis was questioned because of conflicting data from clinical, neuroradiological and neurophysiological testing. In conclusion SEP techniques proved to be a useful tool in exclusing other e.g. demyelinating diseases. Except for the time consuming method of segmental stimulation, the demonstration of the functional deficit itself by SEP techniques in general was frequently disappointing. The contribution of the different SEP parameters to clinical decision making and the clinical consequences are briefly discussed. PMID- 8483519 TI - The operative treatment of spinal deformities in MMC. AB - The results of the operative treatment of scoliosis in 12 patients with MMC and in two patients with associated severe kyphosis are presented. In scoliosis only multi-segmental methods combined with ventral procedures allow a postoperative care without brace or cast. The angle before and after operation with the CDI or CDI/VDS procedures averaged 80.3 degrees and 38.2 degrees respectively (mean corrections of 41.5 degrees and 51.6%). The results show that patients with scoliosis with MMC had a approximately 30% greater preoperative angle than patients with idiopathic scoliosis. An early operation (in progressive curves with more than 30 degrees) may reduce the number and severity of complications. PMID- 8483520 TI - Lipid peroxidation in experimental spinal cord injury: time-level relationship. AB - Damage which occurs following spinal traumas is often irreversible. During recent years free oxygen radicals formed due to the pathological changes following neural tissue ischemia have been identified as being responsible for the ethio pathogenesis of such damage. In our experimental study, model lesions are formed in spinal cords of rats by standard trauma. Malondialdehyde (MDA), a lipid peroxidation product, was measured in the spinal tissues distal to the trauma in order to examine indirectly the time-quantity relationship of free oxygen radicals in the area. For this study 60 rats in six groups, including one control group, were used to determine the formation of MDA. Under a surgical microscope, the spines of all rats were exposed by C5-Th6 laminectomy, and pressure was applied to the spinal cords of animals, except the members of the control group, at the level of C7 by a Yasargil aneurysm clip. MDA was measured in spinal cord tissues in order to determine free oxygen radicals at the first and fifteenth minutes and at the first, second, and fourth hours. The statistical evaluation of the findings revealed a significant increase in MDA, starting from the 15th minute after the compression, reaching a maximum at 1 hour, and then decreasing. This observation may provide an important guide for studies on prevention of neural destruction. PMID- 8483521 TI - Chronic compression of the cervical myelon as complication of anterior interbody fusion (AIF): neurological improvement after late anterior decompression. Case report. AB - Severe neurological deficits directly related to intraoperative injury of the spinal cord and the nerve roots is a rare complication of anterior interbody fusion (AIF) in cervical spondylosis. A case of radiculopathy and Brown-Sequard Syndrome caused by a bone fragment following AIF in which a late anterior decompression and fusion of the cervical spine was performed four years after the initial operation is presented. Immediate relief of the radicular pain, improvement of the spasticity, and better sphincter control could be achieved. Therefore, patients with chronic anterior compression of an incomplete spinal cord injury after AIF may benefit from a late anterior decompression and fusion. PMID- 8483522 TI - Syringomyelia: a brief review of ontogenetic, experimental and clinical aspects. AB - The generally accepted definition of syringomyelia is that it is a chronically progressive illness characterized by the presence of cavities or syrinxes in the spinal cord. As manifold as the terminology of syringomyelia are the hypotheses of the etiology. Nowadays with MRI without and with gadolinium it is possible to recognize intramedullar cavities safely, the MR especially the cine-MR provides information on pathophysiological details of the flow and intracavitary pressure dependent pulsations of the CSF. Animal models and the findings of own experimental studies have enabled us to study a form of syringomyelia which very closely resembles that brought about by dysrhaphic malformations in the human being and to examine the effectiveness of certain types of surgical therapy. In this paper the term syringomyelia is only used for dysrhaphic cavities in the medulla. After our experience with 61 patients with syringomyelia now we perform the operative decompression of the craniocervical transition as the first step in the operative treatment of the progressive syringomyelia combined with severe craniocervical malformations. In cases with insufficient treatment response we suggest the syringoarachnoid shunting of persisting large intramedullar cavities. PMID- 8483524 TI - Play and its relations to other mental functions in the child. PMID- 8483523 TI - Somatosensory and auditory brainstem evoked potentials during choroid plexus angioma removal. AB - Intraoperative combined SEP and BAEP monitoring provides a high level of safety for patients undergoing high risk intracranial surgical procedures. We performed this type of monitoring in a rare case of choroid plexus angioma, embedded into the pulvinar of the right thalamus, which was resected via a transcallosal approach. The SEP pattern deteriorated during parietal brain retraction and thalamic dissection, but never completely disappeared. The BAEP pattern remained unchanged during the entire operation. The patient suffered incomplete hemiparesis postoperatively, but recovered completely within 10 days. After this time the SEP pattern returned to normal. This case points out that pathological change of intraoperative SEP pattern without loss of components suggests an incomplete hemiparesis. There is, however, a good chance of full recovery in the early postoperative period. PMID- 8483526 TI - Ad astra per aspera. PMID- 8483525 TI - Exploratory play with objects: basic cognitive processes and individual differences. PMID- 8483527 TI - No one exempted from the struggle against racism. PMID- 8483528 TI - Why don't men choose nursing? PMID- 8483529 TI - International Rescue Committee confronts Bosnian horrors. PMID- 8483530 TI - Health care reform a politically high-risk venture. PMID- 8483531 TI - How states respond to the rural nursing shortage. PMID- 8483532 TI - The community as partner in primary health care. PMID- 8483533 TI - Nursing's dual role in health care policy. PMID- 8483534 TI - Survivors of the century. AB - Stereotypical views of the elderly hold that very old persons are less adaptable to change and less comfortable handling crisis situations. Over the last five years, we have had the privilege of meeting 96 people aged 100 years or older as part of the National Institute of Mental Health (NIMH) funded, Georgia Centenarian Study (R01 MH 43435-05). We have encountered optimistic, wise individuals very engaged in living. Our research team continues to be amazed at the quality of life and the individual differences amongst centenarians. PMID- 8483535 TI - Why is the AMA complaining? PMID- 8483536 TI - Wrong move. PMID- 8483537 TI - Second chance. PMID- 8483538 TI - Terminating the doctor-patient relationship. When and how. PMID- 8483540 TI - Pages from the past. PMID- 8483539 TI - A leader in dentistry. PMID- 8483541 TI - DSSNY's proud legacy. PMID- 8483542 TI - Reflections on 50 years in dentistry. PMID- 8483543 TI - A future for occupational health nursing: Part 1. PMID- 8483544 TI - Absolute confidentiality--myth or reality. PMID- 8483545 TI - Flu vaccinations: are they worth the cost? AB - Flu immunisation programmes have been offered by many organisations this year and companies will be expecting to see the dividend of reduced absenteeism. But are nonselective vaccinations worth the expense? Helen Kogan weighs up the arguments. PMID- 8483546 TI - 1993--the year of living safely. AB - The Employment Bill aims to safeguard the rights of pregnant workers and those victimised at work on the grounds of health and safety. Gillian Howard, a barrister and industrial relations consultant, examines the new regulations. PMID- 8483547 TI - Plumbo porphyria. A difficult diagnosis. PMID- 8483548 TI - AIDS update. PMID- 8483549 TI - Ill health retirement in health care workers. AB - Discovering why employees take early ill health retirement helps identify areas for future preventive action. Helen Sarfas found important areas for further investigation after initiating a research survey looking at health care workers employed by her health authority. She also discovered that diagrammatic illustration was the easiest and simplest way to present her research data. PMID- 8483550 TI - A future for occupational health nursing: Part 3. AB - Ruth Alston's two previous articles have indicated how some of the current developments occurring in the educational provision for nurses and other health and safety practitioners may affect the practice of occupational health nursing. In this final article she asks whether OHNs are able and willing to respond to the challenges facing their profession and survive in increasingly competitive occupational settings. PMID- 8483551 TI - Carers in crisis. AB - Care in the community has left over six million people with a dual function, however, combining the duties of work with the responsibilities of being a 'carer' might just prove to be too much for many employees. P J Whyte, describes one such example and argues that the skills of an occupational health practitioner can be used to support the growing numbers of carers in our workforce. PMID- 8483552 TI - Protecting against pesticides. PMID- 8483553 TI - Passive smoking: only a question of time. AB - It is believed to be just a question of time before an employee successfully sues a company for the damaging effects of environmental tobacco smoke (ETS). With No Smoking Day on March 10 Helen Kogan looks at current developments in research and new health and safety law that add weight to the calls for more stringent guidance on workplace smoking. PMID- 8483554 TI - Attendance and absence control: whose responsibility? AB - Absence control is a management responsibility, nevertheless, OH can make a valuable contribution to the creation of a supported system. Kit Artus examines management and employee attitudes to absenteeism and presents an argument for a multi-disciplinary approach to the problem. PMID- 8483555 TI - Malingering: a fraudulent issue. PMID- 8483556 TI - Mitomycin: its evolving role in the treatment of breast cancer. AB - Investigators have compiled extensive experience with mitomycin in the treatment of patients with breast cancer. Given as a single agent in intermittent schedules, mitomycin has induced responses of 26-38% in previously untreated patients and of 15-25% in those exposed to multiple prior chemotherapy regimens. Duration of response has been short. Toxicity, primarily myelosuppression, is largely dose-dependent. The dose-dependent efficacy of mitomycin has not yet been addressed. Preclinical studies suggest that optimal single-agent results are obtained when mitomycin is given in intermittent, high-dose schedules. Combination chemotherapy with mitomycin has proven more effective than single agent therapy. Mitomycin given in combination with doxorubicin produces higher response rates than have been obtained with mitomycin alone. The 3M combination (mitomycin/mitoxantrone/methotrexate) appears effective and well tolerated at the doses described. Future research should focus on the development of polychemotherapeutic regimens that can be delivered in sequential or alternating schedules. Such regimens may yield quicker responses, and thus improve survival, in patients with breast cancer. PMID- 8483557 TI - First-line and salvage therapy of metastatic breast cancer with mitomycin/vinblastine. AB - The combination chemotherapy regimen of mitomycin/vinblastine has been used in the treatment of metastatic breast cancer since the early 1980s. We report results of use of mitomycin/vinblastine in 35 women with metastatic breast cancer who had failed prior treatment with one to four chemotherapeutic regimens. Despite heavy prior treatment and significant tumor burdens, 34% of patients achieved a partial remission and another 14% had disease stabilization with a very acceptable toxicity profile. This regimen was also used for the first time as first-line chemotherapy in 11 women with metastatic breast cancer. Response was observed in 9 of 11 patients (82%). Hemolytic-uremic syndrome occurred in 6 of the 46 women (13%) treated in the two protocols and is the most serious potential complication. Mitomycin/vinblastine is an effective salvage regimen and an excellent first-line chemotherapeutic treatment for women with metastatic breast cancer. PMID- 8483558 TI - The use of mitomycin in esophageal cancer. AB - Concurrent administration of chemotherapeutic agents and radiation with or without surgery has yielded better local disease control and more prolonged survival than has standard radiation therapy or surgery alone in patients with esophageal cancer. Combinations of 5-fluorouracil (5-FU) and either cisplatin or mitomycin have proven most effective in this setting. As a single agent, mitomycin has generated response rates of 14-42% in patients with squamous cell carcinoma of the esophagus. The response of patients with esophageal adenocarcinoma to single-agent mitomycin is unknown. The clinical use of mitomycin concurrent with 5-FU and radiation is well established in esophageal cancer. There is some experimental evidence to suggest that synergy may occur between 5-FU and mitomycin. Mitomycin is preferentially cytotoxic to hypoxic cells, which are relatively radioresistant. It is not clear whether use of mitomycin with radiation is additive or supra-additive as experimental evidence exists to support both types of interaction. Nonrandomized clinical trials suggest that using either cisplatin or mitomycin concurrently with 5-FU and relatively low-dose radiation (30 Gy) prior to esophagectomy can result in comparable rates of pathologic complete response (20-30%) and median survival (12 19 months). Hematologic toxicity is frequently severe if all 3 drugs are used concurrently in combination with radiation. In patients with advanced disease (stage III or IV), combination chemotherapy/radiation therapy can result in significant palliation with tolerable morbidity. The use of concurrent chemotherapy and radiation has changed the pattern of failure in esophageal cancer from one dominated by inability to control local disease to one where systemic failure predominates. Current and proposed trials in esophageal cancer have changed their focus accordingly to meet this new treatment challenge. PMID- 8483559 TI - Mitomycin in anal canal carcinoma. AB - One hundred and ten patients with primary epidermoid cancers of the anal canal were treated in a series of prospectively designed, nonrandomized protocols of split-course radiation therapy with concurrent administration of 5-fluorouracil (5-FU) with or without mitomycin. The addition of mitomycin was associated with improved primary tumor control rates (87 vs. 58% at 4 years, p = 0.005) and improved 4-year actuarial cause-specific survival (80 vs. 64%, p = 0.02). Hematologic toxicity was the most frequent acute side effect of mitomycin use. No long-term toxicity was attributed to mitomycin only. Mitomycin appeared to benefit patients principally through improved control of cancer in the irradiated volume; there was no evidence of reduced risk of extrapelvic metastases. Several investigators have reported high rates of control of epidermoid anal cancers with preservation of anorectal function following concurrent treatment with mitomycin, 5-FU, and radiation. Mitomycin's role in anal cancer is being evaluated in a randomized clinical trial by the Radiation Therapy Oncology Group. The mechanisms of any interactions between mitomycin and radiation or other cytotoxic drugs in clinical practice remain to be determined. PMID- 8483560 TI - Mitomycin therapy in gastric cancer. AB - Adenocarcinoma of the stomach remains a significant cause of mortality worldwide. The majority of patients present with stage III or IV disease, negating surgery as a curative option. Numerous drugs have been tested over the past 2 decades in single-agent and combination chemotherapy trials. Given by intravenous bolus, mitomycin has induced responses as high as 63% and as low as 24% in patients with various gastrointestinal malignancies. Mitomycin has also demonstrated efficacy when given in combination with doxorubicin and in the three-drug regimen FAM (5 fluorouracil/doxorubicin/mitomycin). FAM has been explored in multiple phase II and III trials and has become the standard with which many new combinations are compared. Compared with other doxorubicin-containing regimens, it has demonstrated the longest median survival (29.5 weeks) and the lowest incidence of severe toxicity. The addition of semustine or leucovorin to FAM has yielded responses comparable with those attained by FAM alone. In Japan, where treatment of gastric cancer has been more successful, possibly due to earlier diagnosis and more aggressive surgical approaches, mitomycin has been given intraperitoneally during surgery and postoperatively in combination with fluorinated pyrimidines or other agents. Mitomycin will undoubtedly play a role in the development of new approaches to the treatment of gastric cancer. PMID- 8483561 TI - Comparison of single-agent epirubicin and 5-fluorouracil/epirubicin/mitomycin in patients with advanced adenocarcinoma of the pancreas. AB - In a randomized trial we compared single-agent epirubicin with the FEM (5 fluorouracil/epirubicin/mitomycin) combination in patients with locally advanced and/or metastatic adenocarcinoma of the pancreas. Sixty patients previously untreated with radiotherapy or chemotherapy were randomly assigned to receive either 100 mg/m2 epirubicin or FEM in the following doses: 5-fluorouracil, 600 mg/m2 to a maximum of 1 g; epirubicin, 50 mg/m2; mitomycin, 6 mg/m2 to a maximum of 10 mg. Treatment was given every 28 days via intravenous bolus; because of its association with delayed myelotoxicity, mitomycin was given every other cycle. A total of 47 patients are evaluable for toxicity and survival, 22 who received FEM and 25 epirubicin. Preliminary results of this ongoing study show no difference in survival between the two arms. Toxicity has been easily managed. A similar number of patients in each arm had elevated serum bilirubin levels, but dose reductions of 50% allowed all these patients to continue treatment. PMID- 8483562 TI - MMM (mitomycin/mitoxantrone/methotrexate): an effective new regimen in the treatment of metastatic breast cancer. AB - MMM (mitomycin 7-8 mg/m2 i.v.) every 6 weeks; mitoxantrone 7-8 mg/m2 i.v. every 3 weeks; methotrexate 35 mg/m2 i.v. every 3 weeks) is a new combination chemotherapy regimen for advanced breast cancer. It has been compared in two complementary randomized trials with CMF (cyclophosphamide 100 mg orally, days 1 14; methotrexate 35 mg/m2 i.v. days 1 and 8; 5-fluorouracil 1 g i.v. days 1 and 8; courses repeated at 28-day intervals) and VAC (vincristine 1.4 mg/m2 every 3 weeks, anthracycline 30 mg/m2 every 3 weeks, cyclophosphamide 400 mg/m2 every 3 weeks) in patients with advanced metastatic breast cancer. In the first trial, which involved 227 patients, 53% of patients receiving MMM and 49% receiving VAC responded to treatment. There was no significant difference between treatment groups in median response duration or survival. Incidence of neuropathy, alopecia, and nausea and vomiting was significantly higher in patients receiving VAC. Hematologic toxicity was greater in the MMM group. In the second trial, which involved 120 patients, 51% of patients receiving MMM and 60% receiving CMF responded to treatment. Again, there was no significant difference between treatment groups in median response duration or survival. Both regimens were well tolerated with a low incidence of alopecia and serious nausea and vomiting, and there were no significant differences in toxicity. Significant reductions in serial left ventricular ejection fractions occurred in 4 patients given CMF and in 2 given MMM. MMM is an effective, well-tolerated regimen for advanced breast cancer, with toxicity similar to that of CMF and less than that of an anthracycline-containing regimen. PMID- 8483564 TI - The devastation of childhood sexual abuse. PMID- 8483563 TI - Standards for immunization practices endorsed by the Oklahoma Nurses Association. PMID- 8483565 TI - Anti-fibrosis agents, musicians, and the purposes of medical care. PMID- 8483566 TI - Wound healing modulation in glaucoma filtration surgery. AB - In some cases, modulation of wound healing, in association with glaucoma filtration surgery, results in lower postoperative intraocular pressures than would occur without such therapy. Treatments affecting wound healing increase the likelihood of achieving long-term filtration, especially in eyes with a poor surgical prognosis. After summarizing the wound-healing process following filtration procedures, we review the mechanism of action, the effectiveness, and the complications associated with some of the most commonly used wound healing inhibitors and then discuss new alternatives currently under investigation. Although much progress has been made, the challenge remains to develop new drugs or combinations of drugs that are less toxic and can yield more predictable results. PMID- 8483567 TI - Retrobulbar blockade of somatic, motor, and visual nerves by local anesthetics. AB - Somatosensory, motor, and visual sensory blockade were investigated after retrobulbar injection of 3 mL 2% lidocaine, prilocaine, or mepivacaine plus hyaluronidase (15 U/mL) and naphazoline nitrate (1:20,000) in 90 cataract patients (n = 30 per group). Before injection as well as 20 and 90 minutes after injection, and then every 30 minutes, the quality of the retrobulbar blockade was evaluated in terms of the following factors until full recovery of function: (1) corneal sensitivity at the three extraincisional quadrants as determined with an esthesiometer; (2) horizontal and vertical motility, and elevation of the lid; (3) visual acuity on an arbitrary score scale ranging from 0 (no light perception) to 6 (visual acuity > 0.05); and (4) the time required for recovery from retrobulbar anesthesia. The data were analyzed by one- (anesthetic) and two factor (anesthetic and time) analysis of variance. Full somatic recovery of corneal sensitivity occurred within 247 +/- 10.2 minutes after lidocaine, within 221 +/- 9.2 minutes after prilocaine, and within 280 +/- 8.5 minutes after mepivacaine (F = 10.1; P < .0001). Full motor recovery (all muscles) occurred within 290 +/- 5.8 minutes after lidocaine, within 258 +/- 5.7 minutes after prilocaine, and within 295 +/- 4.8 minutes after mepivacaine (F = 13.3, P < .0001). On the average, visual acuity decreased most after mepivacaine and least after lidocaine administration, although the differences between the three anesthetics in this regard were not significant. One patient temporarily lost vision after mepivacaine administration. Overall, the somatosensory and motor blockade were most pronounced after mepivacaine. PMID- 8483568 TI - Transscleral neodymium:YAG cyclophotocoagulation: comparison of 180-degree and 360-degree initial treatments. AB - In order to help clarify how much Neodymium:YAG transscleral cyclophotocoagulation (Nd:YAG CPC) treatment should be given to maximize effectiveness and minimize complications in the treatment of refractory glaucomas, we retrospectively reviewed and compared the results achieved with an initial 180-degree noncontact Nd:YAG CPC treatment with those achieved with an initial 360-degree treatment. Forty-five patients were in the 180-degree group and 21 in the 360-degree group. Mean follow up after the first Nd:YAG CPC treatment was 10.2 +/- 7.5 months. The average pretreatment intraocular pressure (IOP) in the 180-degree group was 33.5 mm Hg. After one treatment, IOP in these patients dropped an average of 8.4 mm Hg and was controlled successfully (5 to 22 mm Hg) in 14 (31%). After a mean of 2.0 treatments, IOP in these patients dropped an average of 15.3 mm Hg, and successful IOP control was ultimately achieved in 35 (78%). The average pretreatment IOP in the 360-degree group was 41.8 mm Hg. After one treatment, IOP in these patients dropped an average of 19.4 mm Hg and was controlled successfully in 11 (52%). After a mean of 1.3 treatments, IOP in these patients dropped an average of 20.7 mm Hg, and successful IOP control was ultimately achieved in 13 (62%). Our study suggests that repeated 180-degree treatments can be successful. However, because we found that IOP was controlled more rapidly with fewer major complications in the 360-degree group, the risk-to benefit ratio may be better for initial 360-degree treatment. PMID- 8483569 TI - Drainage tube implants in the treatment of glaucoma following penetrating keratoplasty. AB - A retrospective review was undertaken to compare outcomes in 26 eyes that underwent penetrating keratoplasty (PKP) and drainage tube surgery (Molteno double-plate implant or Schocket procedure). Drainage tube surgery was performed either before PKP (10 eyes), after PKP (7 eyes), or at the same time as PKP (9 eyes). Mean follow up was 22 months. The average preoperative intraocular pressure (IOP) for all of the eyes was 31 mm Hg; 96% of them achieved a final IOP of less than 18 mm Hg (average, 14 mm Hg on a mean of 0.8 medications). Graft failure occurred in 11/26 (42%). Eight of these eyes were regrafted, and six of these eight have remained clear at a mean follow up of 22 months after regrafting. The overall PKP success rate, including the eyes that underwent repeat PKP, was 81%. Visual acuity remained stable or improved in 70% of the eyes. PMID- 8483570 TI - Oculoplastic uses of cranial bone grafts. AB - Cranial bone grafting for craniofacial reconstruction has gained wide acceptance in recent years and is being used with increasing frequency by ophthalmic plastic surgeons. Alloplastic materials (particularly newer materials such as porous polyethylene, hydroxyapatite, and rigidly fixated metal alloys) have a clear role in orbital reconstruction, and in many oculoplastic applications are the material of choice. However, in certain applications cranial bone grafts may be superior, eg, in managing large posttraumatic or postsurgical orbital defects or orbito sinus defects in the milieu of chronic sinusitis. We describe our current techniques for harvesting full-thickness outer-table grafts and split-thickness periosteally-bound "fish-scale" grafts. Harvesting cranial bone grafts is not without risk and donor site morbidity, and we do not advocate the use of cranial bone grafts in those cases that might be managed as well (or better) with alloplastic material. At the same time, ophthalmic surgeons involved in orbital reconstruction should be familiar with the indications for bone grafts and comfortable with harvesting techniques so that they are not limited when circumstances warrant the use of autogenous material. PMID- 8483571 TI - Basal cell carcinoma originating in the lacrimal canaliculus. PMID- 8483572 TI - Melanocytoma of the ciliary body with scleral extension. AB - A 35-year-old woman had a circumscribed pigmented scleral lesion overlying a pigmented mass in the ciliary body and trabecular meshwork. Sclerectomy and iridocyclectomy were performed. Histologically, the lesion proved to be a melanocytoma. This represents to our knowledge the fourth reported case of scleral extension of a ciliary body melanocytoma. PMID- 8483573 TI - Systemic herpetic infection diagnosed by retinal biopsy. AB - We describe a patient with systemic lupus erythematosus who developed myelopathy, optic neuropathy, retinopathy, and aseptic meningitis unresponsive to immunosuppressive and antimicrobial therapy. Although cultures and brain biopsy were unrevealing, a Herpes virus was suggested by retinal biopsy. The patient recovered dramatically after institution of acyclovir therapy and optic-nerve sheath decompression. This case demonstrates that herpetic retinitis can occur in an iatrogenically suppressed host and underscores the value of tissue diagnosis. PMID- 8483574 TI - Infectious disease risks of fibrin glue. PMID- 8483575 TI - Pump shunt success underscored. PMID- 8483576 TI - Optical performance of decentered bifocal contact lenses. AB - Contact lenses frequently do not center over the pupil. The potential changes in optical performance introduced by poor centration of bifocal contact lenses have only been described previously from theoretical considerations. The present study measured the modulation transfer function (MTF) of rigid concentric-design refractive and rigid diffractive bifocal contact lenses with varying apertures and amounts of decentration. Decentration was shown to have a greater effect on the MTF of the refractive than on the MTF of the diffractive bifocals. The MTF of the refractive bifocals was related to the proportion of the aperture covered by the central optic zone (COZ). Unexpectedly, the MTF of the distance focus of the diffractive bifocal contact lenses was reduced at moderately high spatial frequencies. The practitioner should be aware of the effects of decentration of bifocal contact lenses. PMID- 8483577 TI - Microbial contamination of hydrophilic contact lenses: quantitation and identification of microorganisms associated with contact lenses while on the eye. AB - Previous studies have demonstrated the presence of microorganisms on hydrogel contact lenses under various usage conditions. We conducted this study to quantify and identify viable bacteria and fungi associated with hydrogel contact lenses while on the eye. We removed the lenses from patients' eyes using aseptic techniques and cultured them to identify loosely adherent, as well as lens bound, microorganisms. Lenses were vortexed in a transfer medium (thereafter called the lens extract) and the lenses were then incubated in an agar sandwich separately from the transfer medium. We cultured 108 lenses (82 daily wear and 26 extended wear) from 49 patients. Bacteria were cultured from 38% (41) of the lenses; for 31 of these 41 lenses bacteria were isolated only from the lens extracts (made by vortexing lenses in a transfer medium), suggesting a transient association with the lenses. No fungi were isolated. Counts of less than 10 colony forming units (CFU)/lens were observed on 89% of the lenses. Staphylococcus epidermidis were the most frequently isolated bacteria. A statistically significant relation was observed between increased CFU/lens and increased lens age for extended wear lenses (p = 0.028). PMID- 8483578 TI - Crowding and contrast in amblyopia. AB - The crowding effect, defined as the ratio of visual acuities for letters presented in Snellen (i.e., line) format and isolated-letter format, was measured in the amblyopic eyes of 15 children and 15 adults with unilateral amblyopia. Normal limits were based on data from 20 children and 20 adults with no history of amblyopia. The crowding effect was compared for letters of high (96%) contrast and for letters of low (11%) contrast. We report that amblyopia can differentially affect line and isolated-letter acuity for both high- and low contrast letters. For the patients that show an abnormal crowding effect, this effect can be: (1) significantly stronger, (2) significantly weaker, or (3) not significantly different for high- than for low-contrast letters. These findings are consistent with the hypothesis that the crowding effect is contrast-dependent in some amblyopic eyes of both child and adult unilateral amblyopes. PMID- 8483579 TI - Intraocular pressure in an unselected sample of 6- to 7-year-old Chinese children. AB - Intraocular pressure (IOP) was measured in one-hundred-twenty-three 6- to 7-year old Chinese children. Children who had at least one myopic parent had higher IOP's than children with two nonmyopic parents. There was a trend for myopic children to have higher IOP's than nonmyopic children. PMID- 8483580 TI - Effect of asymmetry on calculations of convergence in prism diopters. AB - Calculations of convergence in units of prism diopters are based on an assumption that convergence is symmetrical, that is, the visual axes intersect on the median plane. The effect of departure from symmetrical convergence is shown to produce systematic errors in calculations of convergence distance, if the convergence angle is constrained to be constant. On the other hand, if the convergence distance is constrained to be constant, departure from symmetry results in a systematic reduction in the convergence angle. Because these errors are disregarded in the specification of convergence in prism diopters, care should be taken in using these units for larger amounts of asymmetrical convergence. PMID- 8483581 TI - Are optometric faculty guilty of ageism? AB - Ageism (negative feelings toward the elderly) is common among health care students and impacts upon the delivery of health care. Education serves to promote positive attitudes toward the elderly and alleviates ageism. As role models, faculty in the health professions influence student attitudes and can affect the development of ageism in students. This study was designed to evaluate whether optometric faculty are guilty of ageism. Twenty-nine optometry faculty and 83 optometry students were surveyed using Palmore's "Facts on Aging Quiz: Part 1" (FAQ1). The mean percent score for faculty was 64.14% as compared to a student mean percent score of 63.96% (p = 0.9422, t-test). The faculty also exhibited a larger anti-age bias than the students. Thus, optometry faculty do possess prejudicial attitudes toward older adults and would benefit from increased education in the field of geriatrics. PMID- 8483582 TI - Clinical study of bendazac lysine for in vivo contact lens cleaning. AB - Bendazac Lysine (BZL), a nonsteroidal anti-inflammatory drug (NSAID), prevents denaturation of proteins secondary to chemical and physical activity. The major protein deposited on soft contact lenses is lysozyme, derived from the preocular tear film. We evaluated the effectiveness of eye drops formulated with BZL for in vivo prevention of proteinaceous deposits on contact lenses and found them to be useful in inhibiting protein deposition during a 6-month clinical trial. PMID- 8483583 TI - Transient rigid lens-induced striae in keratoconus. AB - We have observed spontaneous development of striae and an enhanced visibility of them after placing rigid gas permeable contact lenses on six patients suspected of having early keratoconus. These fine folds subside upon removal of the rigid lens. This observation assists clinicians with the differential diagnosis of irregular astigmatism when the definitive biomicroscopic signs of keratoconus are either not present or are so subtle that their presence is questionable. Although these striae may not occur in all patients suspected of having early keratoconus, we find that observation of the posterior cornea in the presence of a rigid lens will often confirm the diagnosis of keratoconus. We have not seen similar striae in patients whose clinical presentation is not consistent with early keratoconus. PMID- 8483584 TI - Psychophysical comparison of four automated perimeters. AB - It is not unusual for a doctor to detect a field loss on the office perimeter and refer the patient to a setting where a different perimeter is used. In such cases, fields are often repeated because of a lack of "comparability." In this study, we compared the "hill of vision" produced by four major types of perimeters. When possible, we explored alternate user-defined stimulus configurations in order to determine if a rough equivalence could be obtained among the various instruments. Background intensity and target size accounted for many of the differences found in the data. Target color, stimulus duration, and noise had relatively little effect. Despite our stimulus manipulations, subtle (but perhaps significant) differences in the hills of vision remained. PMID- 8483585 TI - Critical review: effects of optical defocus on refractive development and ocular growth and relation to accommodation. AB - Studies of optical defocus on refractive development and ocular growth in animals are presented and discussed in relation to the accommodation hypothesis. None of these studies fully support the accommodation hypothesis. The problems encountered in these studies are also discussed. PMID- 8483586 TI - CCLRU standards for success of daily and extended wear contact lenses. AB - Success in contact lens wear is often judged on the basis of patient "survival" rather than the achievement of satisfactory performance based on specific criteria. In 1971, Sarver and Harris defined a series of standards for successful polymethyl methacrylate (PMMA) lens wear which incorporated criteria for wearing time, comfort, vision, ocular tissue changes, and patient appearance. In this paper we propose a revision of these criteria based on current understanding of the ocular response to contact lens wear. These revised CCLRU (Cornea and Contact Lens Research Unit) standards for success are intended as realistic performance objectives, and can be applied in clinical trials to evaluate and compare the clinical performance of present and future rigid and soft contact lenses, worn for daily and extended wear. PMID- 8483587 TI - Interpupillary distance of females of Arab origin. AB - We have investigated the distant and near interpupillary distance (IPD) of three groups of females of Arab origin. Average values and range of values have been determined for children, young adults, and older adults. Average distant interpupillary distance (FIPD) measurements are compared to those of females of Caucasian (European and American), African-American, and Chinese (Hong Kong and mainland China) origin. Different experimental techniques and some unavailable information about previously studied subjects make conclusive statements about the ethnic variation of IPD difficult to draw. PMID- 8483588 TI - [Definition and clinical importance of thyroiditis]. AB - Regarding the different forms of thyroiditis our knowledge has so significantly grown in the last two decades that their clinical importance has been reevaluated. To-day they are ranged among the most often endocrinological disorders. Namely, it became obvious that the most often causes of the temporary hyper- and hypothyroidism are the most recent recognized forms of subacute thyroiditis, and that producing of permanent hypothyroidism the postpartum form also joined with Hashimoto's thyroiditis as the most often endogenous aetiological factor. The most accepted classification of the large group of thyroiditis is the following: acute, subacute and chronic forms. Beyond these rigorous frames of terminology the individual forms overstep the conventional boundaries relating to time, histology and clinical symptoms; they can overlap of follow each other, even they can appear together at the same time. These can be better understood and explained by the disturbance of immunoregulation, which is detectable or supposed in the majority of discussed disorders. The diagnostic and therapeutical characteristics of different forms of thyroiditis have been made known. PMID- 8483589 TI - [Dobutamine stress echocardiography: a new possibility in the diagnosis of coronary disease]. AB - Authors performed dobutamin stress test since 1987 and combined their examinations with 2D-echocardiography in case of suspected coronary artery disease since October 1991. In this study they report on their experiences obtained in the course of the first 32 examinations. The results of the dobutamine stress echocardiography were analysed on the basis of coronarography which was performed in every patient. According to their observations dobutamine stress echocardiography has very good sensitivity and specificity and it is practically a harmless method, but as it requires instruments, assistants, time and work. Authors recommend the method first of all as a complementary to the physical loading method as well as alternative loading examination. PMID- 8483590 TI - [Statistical data on motor handicapped children, aged 0-18 years, based on a national survey]. AB - A computer-based data processing was made at 6762 motor handicapped children. The data were obtained by questionnaires about the health status, educational, social level and rehabilitation of these children. The authors could state the use of therapeutical equipment, the further need for rehabilitation--specialists and the waiting list for the admission to institutions. The number of registered children was 2.4% of the specific population. The aim of the study was to promote the activity of local self governments, local--and national social security--and health authorities competent in the rehabilitation for the social integration of the Hungarian 0-18 years old motor handicapped persons. PMID- 8483591 TI - [Neonatal neuroblastoma detected by ultrasonic screening]. AB - It was found a solid tumour of 24 x 28 x 31 mm size above the right kidney with ultrasound screening in a three days old newborn. After three days appeared cystic areas inside the tumour, so it was thought to adrenal haemorrhage. The tumour didn't decrease during two months and metastases developed in the liver. The urinary VMA level was normal, the HVA elevated. The MIBG scintigraphy was first negative, after a month pathognostic. The primer tumour and metastases disappeared after cyclophosphamid and Adriablastin treatment. The adrenal neuroblastoma can imitate the adrenal apoplexy, so it's important to control all neonatal adrenal haemorrhage until their disappearance. PMID- 8483592 TI - [Screening and care of pregnancy in diabetics]. PMID- 8483593 TI - [On the 150th anniversary of the birth of Jozsef Fodor (1843-1901)]. PMID- 8483594 TI - [Thoughts on the centenary of the death of Lajos Markusovszky]. PMID- 8483595 TI - [Nursing at the Scheibbs hospital is carried out according to the WHO nursing process model]. PMID- 8483596 TI - [The nursing process--a challenge for all]. PMID- 8483597 TI - [Experiences with the introduction of a coordinated nursing process]. PMID- 8483598 TI - [As time goes by ...]. PMID- 8483599 TI - Drug company sponsorship: blessing or bias? PMID- 8483600 TI - Head and neck cancer and the quality of life. PMID- 8483601 TI - Possible methods of creating a functional neoglottis and of constructing a functionally adequate neolarynx. AB - The intention of the following report is to present a concept for constructing a substitute glottis (neoglottis). The concept evolved over the years on the basis of anatomic studies and in the course of plastic reconstructions on patients. It is based on pedicled grafting of a voluntarily controllable--and hence trainable- musculature that might be transplanted into the larynx attached to a neurovascular pedicle. A rima glottidis might be imitated that could be opened and closed from a neutral position. During sleep the neoglottis would be in a relaxed, spasm-free position. A sensitive and tactile stimulus response ought to be possible, as should variations of the state of tension of the substitute vocal muscles. PMID- 8483602 TI - Is cis-platinum vestibulotoxic? AB - Serial vestibular testing was performed on 34 patients undergoing cis-platinum chemotherapy and 12 age-matched normal subjects. Vestibular testing comprised caloric and low-frequency, sinusoidal rotational testing (0.01 to 0.16 Hz). Test retest variability in the caloric and rotational vestibular assessment of the normal subjects formed the basis for evaluation of subclinical loss of vestibular function within our patient population. In spite of high-dose cis-platinum chemotherapy (100 mg/m2) with cumulative dosages to 1600 mg, no clear evidence of vestibular toxicity was found. PMID- 8483603 TI - The benefits of cochlear implantation in the geriatric population. AB - The deterioration of speech-understanding abilities in the aged that results from factors such as reduced speed and accuracy in processing has been well documented. The purpose of this study was to evaluate whether the geriatric population could benefit from a cochlear implant, despite the possibility of reduced processing abilities. Twenty patients, ages 65 to 85 years, with bilateral profound sensorineural hearing loss received the Nucleus multichannel cochlear prosthesis at NYU Medical Center. All patients underwent extensive preoperative medical and audiologic assessments to determine candidacy. The surgical procedure was well-tolerated by all patients. Mean postoperative test results revealed significant improvements in both auditory performance and quality of life as a result of implant usage. These data support the concept that although a reduction in the processing of sensory stimulation might exist, the elderly can process a new auditory code delivered by means of a cochlear implant. PMID- 8483604 TI - Bone-anchored reconstruction of the irradiated head and neck cancer patient. AB - Titanium implants in facial bones for retention of epitheses or dental bridges were used for reconstruction in cancer patients after tumor surgery. Even heavily irradiated bones could integrate the implants and bear the load from the epithesis. No major complications, such as wound infection, fistulation, or osteoradionecrosis, occurred after implant surgery. There was, however, an increased loss of implants with time after irradiation, especially in the orbital region. When hyperbaric oxygen was used as adjunctive treatment, implant losses were reduced. PMID- 8483605 TI - Kawasaki disease: early presentation to the otolaryngologist. AB - Kawasaki disease is an acute febrile illness of unknown etiology that occurs primarily in childhood. Early diagnosis and treatment can reduce the risk of cardiac complications of Kawasaki disease, which carries a 1% to 2% mortality for cardiovascular events. Clinical features include: (1) fever; (2) conjunctival injection; (3) oral cavity changes; (4) changes in the peripheral extremities; (5) erythematous rash; and (6) cervical adenopathy without suppuration. We describe three cases in detail and survey a series of 42 patients at our institution. Otolaryngologic manifestations were found to occur in the early stages of Kawasaki disease. The otolaryngologist may see these patients early in the disease and should be alert to the signs and symptoms for appropriate diagnosis and treatment. Characteristics of Kawasaki disease, difficulties in diagnosis during the initial febrile stage, and the importance of early diagnosis by the otolaryngologist is stressed. PMID- 8483606 TI - Fluorescein use in the detection of perilymphatic fistula: a study in cats. AB - A stained or colored perilymph would be a valuable tool to otologists for the detection of a perilymph fistula. We studied the effect of intravenously injected fluorescein on the inner ear in seven cats. Still and video photography was used to clearly document our findings. Intravenously injected fluorescein appeared within the soft tissue in less than 1 minute and stayed there for at least 3 1/2 hours. Fluorescence around the round window niche resulted from soft tissue (mucosal) fluorescence and extravasation of interstitial fluid (transudate). No fluorescence of perilymph was detected. Because of this, we do not believe intravenously injected fluorescein is useful in the detection of perilymph fistula. Intrathecal injection caused quick and intense staining of labyrinthine fluid. PMID- 8483607 TI - Laser welding of fascial grafts and its potential application in tympanoplasty: an animal model. AB - This study evaluates the welding effect of argon laser on fascial grafts and its potential application in tympanoplasty. An animal model was designed so that surgically induced perforations of the lumbar fascia of the animals were grafted in an underlay fashion. Each graft was "spot welded" around the circumference of the perforation using a hand-held argon laser. Various lasing parameters were used on different grafts. Control perforations were grafted but not welded. A total of 96 perforations was studied. Weld sites were evaluated both histologically and by tensile strength measurement at the end of surgery, and at 7, 14, and 21 days postoperatively. Comparison with controls showed a higher tensile strength for welded grafts, which was most significant in the early postoperative period (p < 0.001). Histologically, it seems that the basic mechanism of fascial welding involves liquification and denaturation of extravasated proteins at the weld sites. Correlation between the extent of thermal damage on the tissues and the various lasing parameters is described. Based on the well-documented safety of argon laser in otologic surgery, and the successful welding of fascial grafts in this study, argon laser may prove beneficial in welding temporalis fascia grafts in tympanoplasty. PMID- 8483608 TI - Facial paralysis in a benign osseous parotid tumor: a case report. AB - This unique lesion has not been described in the literature so far. It appears to have originated from the base of the skull (i.e., styloid process of the temporal bone). Its pathology was extensively reviewed and it appeared to be a benign proliferative mass, but had produced a total facial nerve paralysis with invasion and destruction of the nerve. Although not palpable clinically, it had invaded the deep lobe of the parotid gland, thus reinforcing the importance of a work-up with CT scans and MR imaging to work-up a facial paralysis of unknown cause lasting more than 6 months. PMID- 8483609 TI - Sebaceous choristoma of the middle ear. PMID- 8483610 TI - Laryngeal infiltrating intramuscular lipoma. PMID- 8483611 TI - Piriform sinus fistula--the role of endoscopy in its management. PMID- 8483613 TI - Eleven excuses for not having a will--what's yours? PMID- 8483612 TI - From the National Institute on Deafness and Other Communication Disorders. PMID- 8483614 TI - Affirmative action revisited for the '90s. PMID- 8483615 TI - Home infusion therapy report. PMID- 8483616 TI - Childhood immunizations: controversy and change. PMID- 8483617 TI - Mothers who use nurse midwives have fewer C-sections, episiotomies and shorter hospital stays. PMID- 8483618 TI - Editorial fairness and the "Cantekin affair". PMID- 8483619 TI - Cephalosporins are superior to penicillin for treatment of streptococcal tonsillopharyngitis: is the difference worth it? PMID- 8483620 TI - Cefpodoxime proxetil vs. penicillin V in pediatric streptococcal pharyngitis/tonsillitis. AB - This multicenter, randomized, parallel treatment, observer-blinded study was designed to evaluate the safety and efficacy of cefpodoxime proxetil (5 mg/kg twice daily for 10 days) compared with penicillin V (13.4 mg/kg three times daily for 10 days) for treatment of Group A streptococcal pharyngitis and tonsillitis in pediatric patients. Clinical and microbiologic results were evaluated before therapy, during therapy (Study Days 3 to 5), at the end of therapy (Study Days 14 to 18) and at long term follow-up (Study Days 30 to 32). Both drugs were well tolerated in 578 patients evaluable for safety. Mild gastrointestinal complaints were noted in 6.7% of 386 cefpodoxime-treated patients and in 5.2% of 192 penicillin-treated patients. In 413 patients evaluable for efficacy, both treatment regimens resulted in comparably favorable clinical outcome; cure rates were 83.8% for 275 cefpodoxime-treated patients and 77.5% for 138 penicillin treated patients. However, eradication of S. pyogenes at end of therapy was significantly higher with cefpodoxime (93.1%) than with penicillin (81.2%) (P < 0.01). Cefpodoxime proxetil provides an effective alternative to penicillin V for the treatment of streptococcal pharyngitis and tonsillitis. PMID- 8483621 TI - How common is whooping cough in a nonvaccinating country? AB - In Sweden general vaccination with a whole cell pertussis vaccine was recommended from 1953. In 1979 the recommendation was withdrawn because the Swedish-made vaccine had become ineffective. In order to determine the incidence of the disease in a nonvaccinating country, 400 children born in 1980 were randomly selected from the population register of Goteborg, Sweden. The parents of the children were interviewed in 1990, when the children were 10 years old. The parents of 377 children could be reached, and of those 372 were not vaccinated against pertussis. Of the nonvaccinated children 61% had experienced clinically typical whooping cough; 195 (119 with and 76 without a history of whooping cough) agreed to donate a serum sample for determination of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin. Of the children with a history of whooping cough, 91% had antibodies against pertussis toxin, as had 64% of the children without a history of disease. All but 3 children had antibodies against filamentous hemagglutinin and all 195 children had antibodies against pertactin. The antibody titers against the 2 last mentioned proteins did not differ between children with and without a history of whooping cough or between children with and without antibodies against pertussis toxin. PMID- 8483622 TI - High attack rates and case fatality during a measles outbreak in groups with religious exemption to vaccination. AB - Beginning in October, 1990, a large measles outbreak involving predominantly unvaccinated preschool age children occurred in Philadelphia. By June, 1991, 938 measles cases had been reported to the Philadelphia Health Department. In addition to these cases, 486 cases and 6 measles-associated deaths occurred between November 4, 1990, and March 24, 1991, among members of 2 Philadelphia church groups that do not accept vaccination. We identified measles cases and collected information on symptoms and potential risk factors for complications. Telephone interviews were conducted to collect demographic and clinical information on measles cases in church member households. We identified 486 measles cases among 892 mostly unvaccinated church members. Age-specific attack rates were highest among children 1 to 4 years of age (94%) and 5 to 14 years of age (91%). Five (83%) of the 6 deaths occurred in females, 3 of whom had underlying illnesses. The overall case-fatality rate was 1.2%. The case-fatality rate was 2% for females, 0.4% for males (P = 0.22), 1.7% for primary cases and 0.7% for secondary household cases (P = 0.67). Only one of the children who died had received medical care. Measles spread rapidly in this group, sparing few susceptible individuals. Lack of medical care and underlying disease appear to have contributed to the high case-fatality rate in the church communities. PMID- 8483623 TI - Investigation of a measles outbreak in a fully vaccinated school population including serum studies before and after revaccination. AB - A measles outbreak in early 1989 among approximately 4200 students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure and to predict the efficacy of a booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively). Vaccination in the first year of life an 13 to 14 years since last vaccination were independent risk factors for being a case. Forty-three (18%) of 239 sera collected from students just before revaccination during the outbreak were negative by enzyme immunoassay; a neutralization assay confirmed these 43 lacked antibody predicting protection against measles infection. Of 43 enzyme immunoassay-negative students 24 gave another blood sample 9 to 10 months after revaccination. Revaccination appeared to reduce the portion of all students with neutralization titers predicting susceptibility to measles illness with rash from 7.9% to 3.0% and left the portion predicted to be susceptible to illness without rash unchanged (45%). PMID- 8483624 TI - Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery. AB - The purposes of this investigation were to characterize the disposition of vancomycin in children undergoing cardiopulmonary bypass (CPB) surgery and to determine whether a 15-mg/kg intravenous dose provides adequate serum concentrations during and after CPB. Six children (age range, 0.8 to 4.8 years) received intravenous vancomycin 15 mg/kg 1 to 2 hours before CPB surgery. Serial blood samples (mean, 10/patient) were collected before, during and after CPB surgery. The mean (+/- SD) vancomycin concentrations at the end of the infusion and 5 hours after the infusion were 27.3 +/- 5.7 and 5.9 +/- 3.0 mg/liter, respectively. The initiation of CPB resulted in an abrupt decrease (44.5%) in serum vancomycin concentrations; however, concentrations remained constant (range, 6.2 to 14.1 mg/liter) throughout the rest of the CPB procedure. The mean (+/- SD) values for the apparent volume of distribution, total body clearance and elimination half-life were 0.59 +/- 0.15 liter/kg, 2.94 +/- 0.93 ml/min/kg and 2.4 +/- 0.8 hours, respectively. These values were similar to those reported in the literature for children not undergoing CPB surgery. A single vancomycin dose of 15 mg/kg before pediatric CPB surgery provides serum concentrations greater than 5 mg/liter throughout the duration of the CPB procedure. To sustain these concentrations subsequent dosing of vancomycin is necessary within 6 hours after the initial vancomycin dose. PMID- 8483625 TI - Pediatric human immunodeficiency virus infection in a low seroprevalence area. AB - Although increasing information is available regarding human immunodeficiency virus (HIV) infections of children in high seroprevalence areas, few data are available describing trends in low seroprevalence populations. In San Diego County approximately 1 in 1450 live births are to women infected with HIV as identified by nonlinked heel stick testing. Seventy-seven HIV-infected children were identified and followed in our clinics during the period 1983 to 1991, of whom 32 (42%) were infected perinatally, 32 (42%) were hemophiliacs and 13 (17%) were infected by blood transfusions. During the last 4 years of the study period (1988 to 1991), most (28 of 37, 76%), newly identified HIV-infected children less than 13 years old were perinatally infected. Of the 32 perinatally infected children 50% were Hispanic, 34% were Caucasian and 16% were African-American. The prospective vertical transmission rate was 16%. Twenty-nine (38%) of the HIV infected children have a diagnosis of acquired immunodeficiency syndrome and 17 (22%) have died. Comparatively few of the HIV-infected hemophiliac patients (4 (12%)) have progressed to an acquired immunodeficiency syndrome diagnosis. The number of acquired immunodeficiency syndrome diagnoses declined in the last 2 years of the study as a result of fewer cases of Pneumocystis carinii pneumonia; 11 cases of P. carinii pneumonia were diagnosed in 1988 to 1989 compared with 4 cases in 1990 to 1991. Survival analysis for the perinatally infected group yielded a median survival of 9.2 years. The apparent trend in our data toward improved outcomes of children infected with HIV suggests the beneficial effects of early identification, antiretroviral treatment, and P. carinii pneumonia prophylaxis. PMID- 8483626 TI - Survival experience of 789 children with the acquired immunodeficiency syndrome. AB - To define predictors of survival we studied longitudinal histories of 789 New York State Medicaid-enrolled children diagnosed with acquired immunodeficiency syndrome (AIDS) from 1983 to 1989 and followed through 1990. Median survival times for 3 severity groups of AIDS-defining conditions were 66, 48 and 9 months. In a proportional hazards model, the relative risk of death for the most vs. least severe group was 3.33 (95% confidence interval, 2.53, 4.37) and the relative risk for children < 6 months old at diagnosis vs. older children was 1.81 (95% confidence interval, 1.41, 2.34). We increased our ability to predict death by using a 4-category severity index that assesses both the AIDS-defining diagnosis and clinical complications within 3 months of diagnosis (relative risk, 5.27; 95% confidence interval, 3.16, 8.78 for most vs. least severe). These analyses offer new clinical severity measures and reveal that, regardless of the AIDS-defining diagnosis, children with AIDS who are < 6 months old have a poor prognosis. PMID- 8483627 TI - The Rhino-Probe nasal curette for detecting respiratory syncytial virus in children. AB - During two outbreaks of respiratory syncytial virus (RSV) infection, 68 children with acute respiratory illnesses were cultured for RSV using a Rhino-Probe (RP) nasal curette and either a nasopharyngeal (NP) swab or a nasal wash (NW). In the first outbreak isolations of RSV by the RP nasal curette and NP swab methods were compared. RSV was cultured from 25 of 42 (60%) subjects using the RP nasal curette and from 20 of 42 (48%) subjects using the NP swab. In the second outbreak the RP nasal curette and the NW collection techniques were compared. RSV was isolated from 15 of 26 (58%) children evaluated. RSV was cultured from 14 of 15 (93%) patients by RP and 13 of 15 (87%) when using NW. In the group of culture positive subjects, the TESTPACK RSV rapid antigen test was positive in 10 of 15 (67%) using the RP and in 6 of 15 (40%) using the NW. Like the NP swab the RP nasal curette was simple, noninvasive and relatively inexpensive, yet it was as sensitive as the NW for detection of RSV. PMID- 8483628 TI - Management of fever in granulocytopenic children with cancer. PMID- 8483629 TI - Diagnostic efficacy of a Mycoplasma pneumoniae hybridization test in nasopharyngeal aspirates of children. PMID- 8483630 TI - Neonatal Blastocystis hominis diarrhea. PMID- 8483631 TI - Congenital toxoplasmosis presenting with eosinophilic meningitis. PMID- 8483632 TI - Pyogenic liver abscess complicating ingestion of sharp objects. PMID- 8483633 TI - Griseofulvin significantly decreases serum salicylate concentrations. PMID- 8483634 TI - Shigellosis complicated by perforated appendix. PMID- 8483635 TI - Bone pain and facial nodule in an adolescent female. PMID- 8483636 TI - Group A beta-hemolytic Streptococcus: issue of resistance. PMID- 8483637 TI - Role of Pseudomonas aeruginosa in chronic suppurative otitis media. PMID- 8483638 TI - Recalcitrant "acute" otitis media secondary to glue ear. PMID- 8483639 TI - Personality characteristics and duration of ATA Taekwondo training. AB - Students in ATA Taekwondo schools were administered the 16 Personality Factor Questionnaire. The students were divided into two groups of 15 persons each based on 0-1.4 yr. vs 1.5 + yr. spent in formal Taekwondo training. From the 16 PF, scores on two second-order and one derived factor were calculated for Anxiety, Independence, and Leadership. The groups having longer Taekwondo training times scored significantly lower on Anxiety and higher on Independence. Although Leadership scores were higher for the longer trained group they were not statistically significant. PMID- 8483640 TI - Critical values for evaluating CELF-R Receptive and Expressive Language Score discrepancies. AB - Psychoeducational evaluation of school-aged children may involve a comparison of examinees' language comprehension and production skills. To facilitate the diagnostic process, this paper presents a table of critical values for the Clinical Evaluation of Language Fundamentals--Revised, which can be used to evaluate the statistical significance of observed-score discrepancies. Theoretical implications of such discrepancies are also discussed. PMID- 8483641 TI - Case's developmental model and children's drawings. AB - 109 children in four age groups were administered two memory measures designed by Case in 1985, the Beery Visual Motor Integration Test and five drawing tasks from Dennis. Scores on working memory were correlated positively with age; children's drawings corresponded to Case's four developmental substages; and a direct relationship was found between the children's drawings and their performance on the psychometric measure of visuomotor integration. These findings are interpreted as evidence that important developmental changes in children's drawing can reliably illuminate changes in intellectual development. PMID- 8483642 TI - Beta-endorphins and mood states during resistance exercise. AB - Research examining the relationship between beta-endorphin immunoreactivity and affect has resulted in equivocal findings. To examine this relationship further, 10 male and 10 female college-age students participated in a controlled free weight exercise session. Blood plasma samples were procured both prior to and following the exercise bout and beta-endorphin levels were determined by immunoassay. Analysis indicated that plasma beta-endorphin levels following exercise were significantly decreased from pre-exercise levels. Pearson correlations showed no significant relationship between pre- or postexercise plasma beta-endorphins and either total mood disturbance or Profile of Mood States subscores. The data support previous failure of resistance exercise to produce an increase in beta-endorphin immunoreactivity as well as the lack of a significant relationship between affect and the beta-endorphin response to exercise. PMID- 8483643 TI - Changes in body size of elite high school football players: 1963-1989. AB - An examination of the heights and weights of members of the Parade Magazine's High School All-American Football Teams from 1963-1971 indicates no significant changes in the Body Mass Index of these elite athletes whereas an increased pattern in Body Mass Index was noted within this group from 1972-1989. The large increases in Body Mass Index after 1971 among the All-American high school football players raise interesting research questions; in particular, what portion of these gains can be attributed to improved nutrition and training techniques and what portion is the result of use of performance enhancing drugs such as anabolic steroids? PMID- 8483644 TI - The mere exposure effect for stimuli presented below recognition threshold: a failure to replicate. AB - Repeated exposure to a stimulus increases one's affect toward that stimulus. This finding, termed the mere exposure effect, has been obtained even when the exposure durations are below the threshold of recognition. Reported are three experiments designed to assess whether the mere exposure effect for stimuli presented below the threshold of recognition could be obtained for meaningful stimuli. Analysis showed that meaningfulness of the stimuli had no effect on ratings of affect; however, we did not replicate previous findings of a mere exposure effect for stimuli that were not recognized. The robustness of the mere exposure effect for stimuli presented below the threshold of awareness was questioned. PMID- 8483645 TI - Self-other differentiation among psychotic and conduct-disordered adolescents as measured by human figure drawings. AB - 24 psychotic-spectrum adolescents were compared with 23 conduct-disordered adolescents on a self-other drawing differentiation task. Of the 24 psychotic spectrum disordered adolescents, 14 received the diagnosis of Psychotic Disorder NOS (Group 1) and the remaining 10 had diagnoses of Schizophrenia, Bipolar Disorder with Psychotic Features, and Schizoaffective Disorder (Group 2). Interestingly, less impaired adolescents (Groups 1 and 3, the conduct-disordered group) showed significantly more difficulty than the more impaired adolescents (Group 2) on self-other differentiation as measured by their differentiated drawings. PMID- 8483646 TI - Force perception before and after maximal voluntary contraction. AB - Capacity to match a low level of elbow flexion force maintained in the control arm was measured in the experimental arm in 16 subjects before and after maximal voluntary contraction (MVC). Prior to a 1-min. MVC, the mean force exerted by the experimental arm was 3.4 +/- 1.0 kg when attempting to match the tension of a 2.3 kg weight in the control arm. After the MVC, the mean force exerted in the experimental arm was 4.4 +/- 2.6 kg. The change in perception of force after a prolonged MVC as demonstrated in this study may be due to postcontraction potentiation of contraction, which has been demonstrated by others after a brief MVC. PMID- 8483647 TI - A replay of the baseball data. AB - Fudin, Renninger, Lembessis, and Hirshon (1993) reported a nonsignificant longevity advantage for right-handers in their analysis of archival baseball data, although the absolute values are still in the predicted direction. Differences in specific data entries and analyses are difficult to resolve; however, there is some indication that the data base that they analyzed differs from that in our study. Further, their use of parametric statistics, given distributional problems and grossly unequal group sizes, may account for the nonsignificance they observed, when compared to the nonparametric analyses that we used. While we considered our original study a pilot project, the literature now contains hundreds of studies that show that left-handedness is associated with a wide range of health-risk factors including serious accidents, immune system disorders, and birth-related complications that involve reduced oxygen. A recent study of the archival records of over 3000 cricket players showed a significant advantage of over 2 years in longevity for right-handed cricket players. On the basis of these findings, we still believe that left-handedness is a marker for reduced longevity. PMID- 8483648 TI - The relationship between trait and precompetitive state anxiety among high school athletes. AB - A sample of 270 tennis players representing 56 high school programs were assessed on competitive trait and state anxiety during the active season. A series of multivariate analyses of variance indicated that highly trait-anxious athletes reported greater cognitive A-state, greater somatic A-state, and lower state self confidence than low trait-anxious athletes. PMID- 8483649 TI - Effects of force output and preparatory period on fractionated reaction time. AB - The effects of force output and its preparatory period on fractionated reaction time were investigated. Eight subjects responded with an isometric elbow flexion to light stimuli under three experimental conditions, adjusting force output to match two target forces (10% or 40% of maximal isometric voluntary elbow flexion strength) displayed on an oscilloscope. Analysis indicates that the relationship between premotor time and force output is affected by preparatory states in the central nervous system, and the preparatory time necessary for exertion of a specific force varies with the magnitude of exerted force. PMID- 8483650 TI - A short measure of self-esteem: some data on reliability. PMID- 8483651 TI - Phonological similarity effect is abolished by a silent mouthing task. AB - This experiment was designed to examine the effect of silent mouthing on the phonological similarity effect. 16 undergraduates were tested for serial recall of visually presented letter sequences that were either phonologically similar or dissimilar. The letter sequences had to be remembered under two conditions, a control condition and a silent mouthing condition in which subjects had to articulate irrelevant words silently during the study period. Analysis showed the clear advantage of the dissimilar sequence over the similar one in the control condition. In contrast, this phonological similarity effect disappeared in the silent mouthing condition. This result is consistent with the working memory model. PMID- 8483652 TI - Control issues and body image in panic disorder. AB - Mean perceived emotional control and body image were compared for 7 subjects with and 6 without panic disorder, all physically healthy. The former had a lower mean on sense of emotional control and showed greater emphasis on the back of the body. These preliminary data encourage replication with a larger group. PMID- 8483653 TI - Personality dynamics of adolescent boys where the father was absent. AB - The effects of substitute adult male role-models were examined for 60 adolescents between the ages of 13 and 18 years. Significant mean differences were found on Depression, Hypochondriasis, and Suspiciousness scales of the MMPI and Guilt and Assaultiveness of the Buss-Durkee Hostility Inventory. Interpretation of scores showed that fatherless boys who had substitute male role-models were similar in personality to boys with fathers. Adolescent boys without fathers and from lower socioeconomic families were significantly more similar in personality to young offenders. PMID- 8483654 TI - Hand preference in the use of tools by infant baboons (Papio cynocephalus anubis). AB - Hand preference in the use of tools was examined in a peer group of five infant baboons, Papio cynocephalus anubis. Hand preference was noted for all subjects on a sponging task and for one subject on a probing task. The baboons exhibited the highest percentage of bimanual actions on the initial segment of each three component task. These results are consistent with the hypothesis that immature nonhuman primates exhibit lateral asymmetries when they use tools and bimanual coordination when they perform complex manipulative tasks. PMID- 8483655 TI - Effects of music on Alzheimer patients. AB - From a large nursing care facility, 60 elderly patients diagnosed as having Alzheimer disease were randomly separated into three groups of equal size and given tests to measure their mood and mental state. For music Group 1, "Big Band" music from the 1920s and 1930s was played during their daily recreation period while Group 2 were given puzzle exercises during their activity sessions. Members of Group 3 participated in the standard recreational activities of drawing and painting. After six months, the questionnaire was again given to all participants. Analysis of variance showed the individuals in Group 1 were more alert, happier, and had higher recall of past personal history than patients in the other two groups. This suggests that music can be of therapeutic value to Alzheimer patients. PMID- 8483656 TI - Failure to demonstrate gender differences in interference to information processing of body-shape stimuli. AB - The Stroop test was adapted to assess disruption to processing of body-shape stimuli. Women are usually considered to be more concerned with personal body shape and weight issues than men. This analysis yielded no differences between men and women when processing body-shapes and weight stimuli. PMID- 8483657 TI - Influence of age, sex, balance, and sport participation on development of throwing by children in grades K-8. AB - The purpose of this study was to examine the contributions of age, sex, balance, and sport participation on development of throwing by children in Grades K-8. The subjects were 381 boys and 338 girls (ages 4-14) enrolled in a medium-sized school system in southeastern Maine. Each subject was individually assessed in throwing development and static and dynamic balance. In addition, all subjects completed a survey relative to their participation in school- or community sponsored sports. To determine the independent effects of age, sex, static balance, dynamic balance, and sport participation within each grade, data were subjected to multiple regression analysis, which indicated that mature throwing development was influenced by sport participation and sex. Boys performed better at all grades. PMID- 8483658 TI - Differential effects of aging on two verbal fluency tasks. AB - The effect of age on verbal fluency was studied in 84 healthy volunteers, ages 45 to 91 years, who performed letter-fluency and semantic-fluency tasks. Older subjects (75 to 91 yr.) performed as well as younger (50 to 64 yr.) on letter fluency but did significantly worse on semantic category fluency. This pattern is similar to that observed in Alzheimer-type dementia. PMID- 8483659 TI - Self-generated mnemonics for number recall in young and old adults. AB - Self-generated strategies for recall of number facts were examined in 164 adults who ranged in age from 20 to 86 years. Participants recalled a number list that included six 2-digit prices and six 4-digit phone numbers. Following recall, participants reported their encoding strategies. A larger percentage of the younger subjects (< 49 yr.) reported using a specific verbal mediator to facilitate encoding, and younger subjects recalled more 2-digit and 4-digit numbers. Across age groups, the self-reported use of encoding strategies facilitated recall. PMID- 8483660 TI - Self-concepts of Nigerian adolescents. PMID- 8483661 TI - Theoretical parallels between the Ponzo illusion and the Wundt-Jastrow illusion. AB - Misapplied-size-constancy, assimilation, and contrast theories are discussed as explanations for the Wundt-Jastrow and Ponzo illusions. An experiment is reported that questions the need to include a contrast function in the assimilation theory of Pressey and Wilson to account for the Wundt-Jastrow illusion. Several directions for further research are proposed. PMID- 8483662 TI - Laterality effects for music perception among differentially talented adolescents. AB - To examine the comparative nature of laterality patterns for music perception among differentially talented adolescents, 138 right-handed subjects (56 boys, 82 girls) trained in music, mathematics, and dance, respectively, were tested on dichotic chords and dichotic melodies tasks. Analyses demonstrated that only the musically trained subjects displayed task-dependent ear asymmetry, that is, a left-ear advantage for dichotic chords and a right-ear advantage for dichotic melodies. The mathematically and dance-talented students displayed a left-ear bias for both tasks of music perception. A control dichotic speech task showed a right-ear bias for all talent groups. The findings speak to how sensory information is managed by the mental-processing systems of differentially talented students and how talent training plays a role in shaping ear asymmetry. PMID- 8483663 TI - Scores on exercise dependence among dancers. AB - A number of researchers have suggested that the syndrome of exercise dependence (addiction) is paralleled by a tendency towards eating disorders such as anorexia nervosa and bulimia. As considerable research has reported a high incidence of eating disorders among dancers and as rigorous physical demands are inherent in dance, we hypothesized that dancers would present a higher profile of exercise dependence on the Negative Addiction Scale than other athletes. To test this hypothesis, 47 female ballet and modern dancers completed a survey on exercise dependence adapted from Hailey and Bailey (1982) to assess quantitatively exercise dependence. Scores were compared with those obtained from 39 female endurance (running) athletes and 16 female nonendurance (field hockey) athletes. Significantly higher scores on dependence for dancers than for endurance or nonendurance athletes were noted. The data indicate that dancers may be at greater risk for psychophysiological problems associated with exercise dependence than other athletes and so should be monitored for symptoms. PMID- 8483664 TI - Handedness and sexual preference: a re-analysis of data presented by Rosenstein and Bigler. AB - Rosenstein and Bigler reported in 1987 that sexual orientation (exclusively versus nonexclusively heterosexual) was not related to right- versus nonright handedness. However, re-analysis of their published data indicated that nonexclusive heterosexuals were 3.13 times more likely to be nonright-handed than were exclusively heterosexual subjects (p < .03). PMID- 8483665 TI - Body satisfaction and self-concept of third- and sixth-grade students. AB - Pubertal development has been implicated as the point of origin for decreased body satisfaction and self-concept for girls from prepubertal levels and an increase in body satisfaction and self-concept for boys. Two groups of boys and girls in Grades 3 and 6 completed a Body Satisfaction Questionnaire and the Piers Harris Self-concept Scale to test this assumption. The third graders were considered to be prepubertal and sixth graders as early pubertal. The sixth-grade boys scored lower on body satisfaction than third-grade boys, and their self concept scores were positively correlated with body satisfaction scores. For girls, body satisfaction scores were correlated with self-concept in both grades, and few significant differences were found between grades. For girls apparently the relationship between body satisfaction and self-concept may be present before the onset of puberty. PMID- 8483666 TI - Gender differences in test anxiety among South African university students. AB - Prior research has shown a sex difference in scores on test anxiety, with men having a lower mean score than women. The present study was undertaken to confirm such a difference among African university students, but the t ratio was nonsignificant for means of 28.4 for men and 28.0 for women (SDs of 5.3 and 5.0). PMID- 8483667 TI - Geophysical variables and behavior: LXXI. Differential contribution of geomagnetic activity to paranormal experiences concerning death and crisis: an alternative to the ESP hypothesis. AB - A total of 621 reports (experienced over an approximately 70-year period) of putative psi experiences concerning death or crisis were differentiated according to traditional labels: telepathic, precognitive, and postmortem phenomena. The 232 telepathic experiences occurred during 24-hour periods in which the global geomagnetic activity was significantly less (quieter) than during the days before or after the experiences; this relationship was not displayed by the 186 precognitive or 203 postmortem cases. Key day differences in geomagnetic activity for the three classes of experiences were equivalent to a correlation of about 0.35. Although content analysis suggests that nocturnal psi experiences and temporal lobe epilepsy may share a similar mechanism, different classes of subjective psi experiences may not be affected by the same stimuli. PMID- 8483668 TI - Emotional behavior during the learning of a contingency task in a chimpanzee. AB - A female chimpanzee's behavior was videotaped during the learning of contingency tasks and used to code her facial expressions, vocal expressions, and other behavior. The chimpanzee showed negative emotional behaviors to negative feedback and seemed to depend not only on the lack of food as reward. The most negative emotional situation for the chimpanzee seemed to be one in which she made an error. PMID- 8483669 TI - Dimensions of Sensation Seeking Scale Form VI: cross-cultural comparison. AB - In this study the factor structure of the Sensation Seeking Scale Form VI was compared for the Kuwaiti and American subjects. Thrill and adventure seeking Factor, Part II Intention, showed good cross-cultural reliability for men only. The differences between findings of this analysis and that of Zuckerman could be interpreted as evidence of cultural differences between Kuwaiti and American subjects in sensation seeking. PMID- 8483670 TI - Hassles, uplifts, and quality of sleep. AB - This study examined whether events which occur during the previous day affect sleeping behavior. Specifically, whether minor irritants (hassles), positive experiences (uplifts), or both hassles and uplifts of the previous day affect night sleep for people without sleeping disorders. 41 subjects completed the Hassles and Uplifts scale as well as four questions (which were combined into a total score) assessing quality of sleep. Quality of sleep was correlated with scores on Hassles and Uplifts (.36), Hassles (.34), and Uplifts (.30). When the sample was divided into good and bad sleepers, correlations with Hassles, and Hassles and Uplifts were significant, but not Uplifts. PMID- 8483671 TI - The Easter bunny in October: is it disguised as a duck? AB - To study the influence of motivational expectancy on perception, the ambiguous drawing of a duck/rabbit was shown to 265 subjects on Easter and to 276 subjects in October. The ambiguous drawing, though perceived as a bird by a majority of subjects in October, was most frequently named a bunny on Easter. This biasing effect of expectancy upon perception was observed for young children (2 to 10 years) as well as for older subjects (11 to 93 years). PMID- 8483672 TI - Age and test anxiety among African university students. AB - As studies in Western countries have shown, scores on test anxiety increase with age during elementary school. Whether such a difference would be observed among African university students who ranged in age from 18 to 35 years was examined. The difference in mean scores on the Achievement Anxiety Test for two groups, ages 18 to 25 years (n = 132) and 26 to 35 years (n = 267), was not statistically significant. PMID- 8483673 TI - Children's creative thinking and color discrimination. AB - 60 children in Grades 3 through 6 from two schools were administered the Farnsworth Munsell 100-Hue Test and teachers provided a measure of different aspects of each child's creative thinking on the Williams Scale of Children's Divergent Thinking. Fluency and imagination scores were positively associated with color discrimination. While other dimensions of creative thinking did not correlate with color discrimination, some correlations suggested thematic connections between color discrimination and other manifestations of creative thinking as evaluated by teachers. Color discrimination was also positively associated with age, as older children differentiated between small differences in colors better than younger children. As intelligence or other variables may be relevant, further study is needed. PMID- 8483674 TI - Time perception: effects of task speed and delay. AB - The study examined the effect of task speed and delay on the perception of time. 60 subjects were randomly allocated to four groups in a 2 x 2 design. The first factor related to the speed of the task (fast or slow) undertaken during the time to be estimated, while the second factor related to when time estimates were obtained (immediately after the task versus following a delay). Analysis supported the hypothesised interaction, with time estimates being shorter in the fast than in the slow condition when obtained immediately after the task but longer in the fast than the slow condition when obtained after a delay. Results are discussed in relation to cognitive theories of time perception. PMID- 8483675 TI - Young children's human figure drawings and cognitive development. AB - The age-stage relationship between young children's human figure drawings and Piaget's levels of cognitive development was investigated using 45 young children ages 4 through 6 years. Analyses indicated a distinct monotonic trend between cognitive stage and drawing level; as cognitive ability increased so did drawing level. This suggests that children's human figure drawings can be a simple tool for the quick assessment of cognitive levels in young children. PMID- 8483676 TI - Children's perceptions of responsibility: attitudes while working with peers with disabilities. AB - The purpose of this study was to examine whether participation in a community based cooperative learning program affected attitudes toward responsibility of 13 talented and gifted students toward 49 peers with disabilities. A survey was administered to measure role perception of these students as they interacted in gross motor recreational activities with students with disabilities. There was a significant difference between pre- and posttest scores on three of six attitude items. Ordinal data suggested the gifted subjects showed an increase in their felt responsibility in this cooperative learning. PMID- 8483677 TI - A dynamic balance measure for persons with severe and profound mental retardation. AB - The present study's purpose was to probe into the reliability and validity measurement of dynamic balance for individuals with IQs below 29. The 91 subjects were asked to complete the Papcsy-DePaepe test and the Bruininks test according to each test's protocol. Correlations of odd-even scores produced a reliability of .98 for the Papcsy-DePaepe test. Concurrent validity was indicated by a Pearson product-moment correlation of .64 between the two tests. Subsequent 3 x 2 x 2 multivariate analyses of variance confirmed a significant difference between the two tests and that retardation was associated with balance performance although age and gender were not. PMID- 8483678 TI - Profiles of Hispanic adolescents and adults on the Myers-Briggs type indicator. PMID- 8483679 TI - Pleasantness-unpleasantness of environmental sounds and gender difference in evaluation. AB - The present experiment examined emotional evaluation of 40 environmental sounds which were presented to 388 college students in a lecture room. Students were required to rate pleasantness-unpleasantness, to identify the sounds, and to rate their confidence about their identifications. Analysis showed that the pleasant sounds were natural and musical sounds and that the unpleasant sounds were sounds of a belch, of a dentist's drill, and of scratching on a blackboard. It is interesting that for pleasant sounds confidence was always high, which suggested that emotional evaluation of the environmental sounds was closely related to the confidence of observers in their identifications of the sounds. Gender differences were noted on the ratings on pleasantness-unpleasantness of environmental sounds, that is, women evaluated the pleasant sounds as more pleasant than men, and men evaluated the unpleasant sounds as not so unpleasant as did women. PMID- 8483680 TI - Blocking and countering in traditional Shotokan karate kata. AB - Analysis of the 1183 techniques forming the twenty-seven Shotokan karate kata (forms) widely practised today shows a significant preference for blocking over counter-offensive techniques. This may be interpreted as evidence to support Karate-do as a Way of self-defense and non-violence. PMID- 8483681 TI - Validation of criterion-referenced archery cutting scores. AB - This study investigated an empirical method for setting optimal cutting scores for a criterion-referenced archery test. The classification-outcome probabilities and approaches to validity suggested by Berk were utilized. Pretest scores were obtained on 35 uninstructed college-age women on six ends (six arrows each) from 20 yards (18.3 m) after an unrecorded warm-up end. Posttest scores were after 15 weeks of instruction. Score distributions were the primary determinant for accurately classifying students as true mastery and true nonmastery. Accuracy is a function of the amount of overlap between distributions. Using the point at which the distributions overlapped, classification accuracy was estimated. Probabilities associated with 80 points were p(TM) + p(TN) = .83 and p(FM) + p(FN) = .14. Scores above and below 80 points had lower probabilities of classification accuracy. Reliability estimated using Kappa was .59. Statistical validity of the cutting score (phi) was .68. PMID- 8483682 TI - Does motor cerebral dominance develop secondary to sensory dominance? AB - Current research and theoretical frameworks for understanding motor dominance assume that motor dominance is primary. Various developmental clues, however, suggest that the maturation of proprioceptive sensory processing predates that of motor control. We hypothesized that the observed adult pattern of lateralized motor dominance may develop as a consequence of preexisting lateralized "sensory" or "proprioceptive dominance." To test whether motor preference could develop in response to sensory dominance, we investigated sighting eye dominance, eye lid winking, and handedness in 164 individuals. Subjects winked the nondominant eye significantly more frequently than the dominant eye and independently of their handedness, lending partial support to the idea that motor function can develop in response to sensory function. Specific investigation of the development of the proprioceptive system would be needed to evaluate whether lateralization of motor handedness develops as a consequence of "proprioceptive" lateralization. PMID- 8483683 TI - Frame-and-spot-induced motion: range effects and the difference between fixation and nonfixation of the induced stimulus. AB - For frame-and-spot-induced linear motion, Humber and Sherrick report that induced motion of a nonfixated static spot reduces as its separation from a fixated static spot increases. The authors invoke sensory factors, but range effects may undermine this interpretation. PMID- 8483684 TI - Attention and visual dominance in motor learning. AB - Two experiments examined the role of attention in visual dominance during motor learning. On the movement task 10 acquisition trials were given; each included a movement presentation and a blindfolded reproduction. After completion of acquisition trials and a 5-min. interval, subjects were given 5 retention trials with reproduction attempts only. In Exp. 1, subjects receiving only kinesthetic information during movement presentation reproduced criterion movement length more accurately than subjects receiving visual and kinesthetic information. Other subjects, presented both visual and kinesthetic stimuli for the movement, were given instructions to ignore vision and focus on kinesthesis. These subjects exhibited no effects of visual dominance in reproductions. In Exp. 2, subjects were presented visual and kinesthetic stimuli during half of the movement presentations and only kinesthetic stimuli during the other half. They did not exhibit the effects of visual dominance in reproductions. Such effects in motor learning may be modified by manipulation of attention or an alternating presentation of specific sensory stimuli. PMID- 8483685 TI - A dominant-subordinate unit-against-unit theory of decreases in visibility. AB - When simultaneous stimuli or stimuli in metacontrast and related research are perceived (recognized, apprehended) as two different phenomenal groups (wholes, things), the visibility of the group with less intense, smaller, no-onsetting, terminating, and briefer features decreases. This decrease also occurs when one of two groups with equally intense, etc. features is made less visible through masking. Therefore, the relative visibility of two groups predicts a decrease in the visibility of one of them better than does their relative intensity, etc. Further, (1) the visibility of all the parts (perceived features, attributes) of both groups is similarly affected, so each group functions as one entity and (2) decreases in visibility are eliminated when stimuli produce only one group. The theory: a neural unit underlies the perception of one group and its parts, and two such units underlie the perception of two groups and their parts (one unit for each group). In addition, the unit for a dominant (high visibility) group inhibits the unit for a subordinate (low visibility) group, thereby decreasing the visibility of the subordinate group. Also, when stimuli produce only one group (hence one unit), unit-against-unit inhibition and hence a decrease in visibility is precluded. PMID- 8483686 TI - Effects of depressed mood on social perception. PMID- 8483687 TI - Variable word initial and medial consonant relationships in children's speech sound articulation. AB - The heterogeneous nature of consonants in the medial position of words may have prevented earlier studies from depicting a clear phonetic relationship between them and consonants in the initial and final positions. In this study, auditory perceptual judgments of children's consonant productions in the initial position of words were compared with those on medial consonants varying in number and order. Neither the perceived frequency of correct articulation nor the error pattern differentiated single consonants in the initial and medial positions of words at any age. Performance on consonant blends in the initial position of words differed from that on both types of medial sequences, but it was more similar to medial consonant sequences that corresponded with permissible word initial blends than to those that did not. It was concluded that initial and medial consonants may be regarded as performance equivalents only under certain conditions. PMID- 8483688 TI - Use of visual feedback during rapid aiming at a moving target. PMID- 8483689 TI - A "fair" comparison of progressive and imaginal relaxation. AB - Progressive and imaginal relaxation-training procedures are difficult to compare because the latter takes many forms. In this study, an imaginal procedure was used that closely followed progressive operations except that muscle tension was imagined rather than experienced. The dependent variable was the total score on the Relaxation Inventory. College students were placed in groups (ns = 50) high and low on suggestibility based on scores on the Creative Imagination Scale, assigned in equal numbers to the imaginal and progressive relaxation conditions and given four sessions of relaxation training. The pre- and posttrials effects were significant within each of the four training sessions. There were no significant differences in reports of relaxation by the progressive and imaginal treatments. The expected cumulative effect of relaxation training across the four sessions was not found; in fact, the imaginal condition showed a significant decrease. The only significant suggestibility effect was an interaction between suggestibility and trials in which highly suggestible subjects reported less pre session relaxation. These results are consistent with reports of no differences between progressive and imaginal relaxation training. PMID- 8483690 TI - Association between physical activity and blood pressure in normotensive adults. PMID- 8483692 TI - The perceptual analysis of structure from motion for rotating objects undergoing affine stretching transformations. AB - In two experiments, we evaluated the ability of human observers to make use of second-order temporal relations across three or more views of an apparent motion sequence for the perceptual analysis of three-dimensional form. Ratings of perceived rigidity were obtained in Experiment 1 for objects rotating in depth that were simultaneously subjected to sinusoidal affine stretching transformations along the line of sight or in a direction parallel to the image plane. Such transformations are theoretically interesting because they cannot be detected by analyses that are restricted to first-order temporal relations (i.e., two views), but they can be detected by more conventional analyses of structure from motion in which second-order temporal relations over three or more views are used. The current results show that human observers can perceive stretching transformations of a rotating 3-D object in a direction parallel to the image plane but that they fail to perceive stretching transformations along the line of sight. This result suggests that human observers can make use of some limited second-order temporal information. This finding was confirmed in Experiment 2, in which we investigated the effects of several specific optical consequences of sinusoidal stretching transformations applied in different directions. The results indicate that observers may be sensitive to the sign of acceleration, but that they cannot make use of the precise magnitude of second-order relations necessary to recover euclidean metric structure. PMID- 8483691 TI - Neural dynamics of motion perception: direction fields, apertures, and resonant grouping. AB - A neural network model of global motion segmentation by visual cortex is described. Called the motion boundary contour system (BCS), the model clarifies how ambiguous local movements on a complex moving shape are actively reorganized into a coherent global motion signal. Unlike many previous researchers, we analyze how a coherent motion signal is imparted to all regions of a moving figure, not only to regions at which unambiguous motion signals exist. The model hereby suggests a solution to the global aperture problem. The motion BCS describes how preprocessing of motion signals by a motion oriented contrast (MOC) filter is joined to long-range cooperative grouping mechanisms in a motion cooperative-competitive (MOCC) loop to control phenomena such as motion capture. The motion BCS is computed in parallel with the static BCS of Grossberg and Mingolla (1985a, 1985b, 1987). Homologous properties of the motion BCS and the static BCS, specialized to process motion directions and static orientations, respectively, support a unified explanation of many data about static form perception and motion form perception that have heretofore been unexplained or treated separately. Predictions about microscopic computational differences of the parallel cortical streams V1-->MT and V1-->V2-->MT are made--notably, the magnocellular thick stripe and parvocellular interstripe streams. It is shown how the motion BCS can compute motion directions that may be synthesized from multiple orientations with opposite directions of contrast. Interactions of model simple cells, complex cells, hyper-complex cells, and bipole cells are described, with special emphasis given to new functional roles in direction disambiguation for endstopping at multiple processing stages and to the dynamic interplay of spatially short-range and long-range interactions. PMID- 8483693 TI - The harmonic bandwidth of phase-reversal discrimination. AB - Previous studies have shown that 180 degrees relative phase shifts in f + 2f gratings are discriminated when the cosine or the sine component of the shift exceeds some criterion (Bennett & Banks, 1987; Field & Nachmias, 1984). The current experiments demonstrate that this result holds for other two-component gratings, provided that the components are within two to three octaves of each other. For frequency differences greater than two to three octaves, phase reversal discrimination is impossible. A simple model that discriminates phase shifts on the basis of changes in the responses of even- and odd-symmetric spatial filters can account for the results. PMID- 8483694 TI - Postsaccadic processing of the retinal image during picture scanning. AB - Eye movements were monitored while observers inspected photographs of natural scenes. At the end of each saccade (i.e., at the beginning of each period of steady fixation), the stimulus was replaced for a certain period of time by a uniform field (Experiment 1) or a blurred version of the stimulus scene (Experiment 2). Total fixation duration was measured as a function of the duration of the initial uniform field or the blurred image that followed the saccade. It was found that fixation duration increased proportionally with the duration of the initial replacement field, even for durations as short as 25 msec. These results suggest that the visual system uses information on the retina right after each saccade is completed and that the blurred, low-resolution information used in Experiment 2 (cutoff frequency of 0.8 cpd) is not sufficient for the requirements of picture processing in this task. PMID- 8483695 TI - The role of haptic versus visual volume cues in the size-weight illusion. AB - Three experiments establish the size-weight illusion as a primarily haptic phenomenon, despite its having been more traditionally considered an example of vision influencing haptic processing. Experiment 1 documents, across a broad range of stimulus weights and volumes, the existence of a purely haptic size weight illusion, equal in strength to the traditional illusion. Experiment 2 demonstrates that haptic volume cues are both sufficient and necessary for a full strength illusion. In contrast, visual volume cues are merely sufficient, and produce a relatively weaker effect. Experiment 3 establishes that congenitally blind subjects experience an effect as powerful as that of blindfolded sighted observers, thus demonstrating that visual imagery is also unnecessary for a robust size-weight illusion. The results are discussed in terms of their implications for both sensory and cognitive theories of the size-weight illusion. Applications of this work to a human factors design and to sensor-based systems for robotic manipulation are also briefly considered. PMID- 8483696 TI - Perceiving heading with different retinal regions and types of optic flow. AB - We examined the ability to use optic flow to judge heading when different parts of the retina are stimulated and when the specified heading is in different directions relative to the display. To do so, we manipulated retinal eccentricity (the angle between the fovea and the center of the stimulus) and heading eccentricity (the angle between the specified heading and the center of the stimulus) independently. Observers viewed two sequences of moving dots that simulated translation through a random cloud of dots. They reported whether the direction of translation--the heading--in the second sequence was to the left or right of the direction in the first sequence. The results revealed a large and consistent effect of heading eccentricity: Judgments were much more accurate with radial flow fields (small heading eccentricities) than with lamellar fields (large heading eccentricities), regardless of the part of the retina being stimulated. The results also revealed a smaller and less consistent effect of retinal eccentricity: With radial flow (small heading eccentricities), judgments were more accurate when the stimulus was presented near the fovea. The variation of heading thresholds from radial to lamellar flow fields is predicted by a simple model of two-dimensional motion discrimination. The fact that the predictions are accurate implies that the human visual system is equally efficient at processing radial and lamellar flow fields. In addition, efficiency is reasonably constant no matter what part of the retina is being stimulated. PMID- 8483697 TI - A ratio principle for a red/green and a yellow/blue channel? AB - There is strong empirical evidence that, under adaptation to another achromatic color stimulus, the lightness of an achromatic color stimulus depends on the ratio of the luminances of the two stimuli. In the present study, the suitability of this ratio principle is tested for two chromatic postreceptoral opponent channels. A Hering red/green channel and a non-Hering yellow/blue channel are specified as chromatic channels. The yellow/blue channel is defined by extrapolating the plane corresponding to unique green-white linearly to the reddish part of color space, using the plane's surface as the channel's equilibria. The experiment was run on an isoluminant plane, measured individually for each observer. Moving along an observer's measured opponent axes, eight adaptation stimuli were selected for each channel and spanned the whole range of the channel's coordinates. Red/green equilibria or yellow/blue equilibria were measured as excursions along the adaptation axes. For both presumed channels, the ratios of the equilibrium coordinates of test and adaptation stimuli were essentially constant. This supports the principle's suitability. However, small asymmetries were found with respect to each channel's opponent hues. The status of the proposed yellow/blue channel is discussed, as are conditions that might have favored the present findings. PMID- 8483698 TI - An element in the visual field is just a conjunction of attributes: a critique of Bundesen (1991) AB - Nissen (1985) presented results showing that in partial-report experiments, selection by location was different from selection by color or by shape. Bundesen (1991) presented a reinterpretation of these results, claiming that they can also be explained by a model in which location selection is treated on a par with selection by color or by shape. We will show that the analysis given by Bundesen is based on a special relation between an "element" in the visual field and its location, which in fact reduces the expressions given by Bundesen to those given by Nissen. Furthermore, we will show that in Bundesen's theory, it is assumed that in the process of perceptual categorization an element in the visual field can be referred to without the use of one of its attributes. This assumption is untenable from a theoretical point of view. In all, the results presented by Nissen can still be regarded as evidence for the difference between selection by location and selection by color or by shape. PMID- 8483699 TI - Dividing attention between color and shape: evidence of coactivation. AB - When attention is divided between spatially distinct objects, the time to detect a target decreases when two or more targets are present. This redundancy gain can be accounted for by an interactive race model (Mordkoff & Yantis, 1991) in which separate decisions are made about each object, but environmental contingencies among the objects can influence decision times. In the present study, we examined whether the model also accounts for performance when attention must be divided between stimulus attributes other than spatial location. Subjects made target present responses when displays included a prespecified color, a prespecified letter, or both target features. The data violated the predictions of all separate-activations models, including the interactive race model. Two control experiments ruled out an alternative account based on task complexity. We conclude that coactivation occurs when target attributes from two separable dimensions are simultaneously present, but not when target attributes come from the same dimension. A modular hybrid of race and coactivation models is tentatively proposed. PMID- 8483700 TI - Moving phantom visibility as a function of fundus pigmentation. AB - Moving phantom visibility was measured for subjects with a fundus classified as either lightly or darkly pigmented. The phantom-inducing pattern was a black-and white square-wave grating drifting continuously from left to right, with a black horizontal occluder interrupting the middle of the grating. Moving phantom visibility was significantly reduced for darker relative to lighter pigmented subjects. The results show that fundus pigmentation can influence the perception of illusory contours and surfaces (i.e., phantoms). This finding supports and expands on previous research concerning fundus pigmentation influences on real contour perception. PMID- 8483701 TI - Saccadic overhead: information-processing time with and without saccades. AB - Information-processing time was compared for serial and spatially distributed visual presentations with performance measures that permit the separation of total time into its during-display and post-display components. For all subjects, there was a significant saccadic overhead, that is, less time was required with the serial format, which allowed data access without eye movements. However, the magnitude of the overhead decreased as task complexity increased. All subjects were able to exercise some control over the distribution of total processing time, trading off short during-display times with longer post-display times and vice versa. PMID- 8483702 TI - Looking for two targets at the same time: one search or two? AB - A considerable amount of evidence suggests that, under conditions of high discriminability, subjects are able to process multiple elements in a visual display simultaneously when searching for a single target among distractors. Relatively little emphasis, however has been placed on the question of whether subjects can search for and detect multiple targets simultaneously. This latter question is the focus of the present report. In two experiments, we compare performance in single-target and multiple-target detection tasks in order to investigate whether or not multiple targets can be detected simultaneously. In Experiment 1, subjects searched for one or two targets that were defined by color. In Experiment 2, subjects searched for a color and/or a letter target. When the two targets were presented in the same location (e.g., a red X when Target 1 was red and Target 2 was an X), they seemed to be detected simultaneously. Implications for object-based processing of visual information are discussed. PMID- 8483703 TI - Feature processing during high-rate auditory selective attention. AB - Auditory event-related brain potentials (ERPs) and reaction times were analyzed in a selective attention task in which subjects attended to tone pips presented at high rates (interstimulus intervals [ISIs] of 40-200 msec). Subjects responded to infrequent target tones of a specified frequency (250 or 4000 Hz) and location (left or right ear) that were louder than otherwise identical tones presented randomly to the left and right ears. Negative difference (Nd) waves were isolated by subtracting ERPs to tones with no target features from ERPs to the same tones when they shared target location, frequency, or both frequency and location cues. Nd waves began 60-70 msec after tone onset and lasted until 250-350 msec after tone onset, even for tones with single attended cues. The duration of Nd waves exceeded the ISIs between successive tones, implying that several stimuli underwent concurrent analysis. Nd waves associated with frequency processing had scalp distributions different from those associated with location processing, implying that the features were analyzed in distinct cortical areas. Nd waves specific to auditory feature conjunction were isolated. These began at latencies of 110-120 msec, some 30-40 msec after the Nds to single features. The relative timing of the different Nd waves suggests that auditory feature conjunction begins after a brief parallel analysis of individual features but before feature analysis is complete. PMID- 8483704 TI - Evaluating a computational model of perceptual grouping by proximity. AB - A formal approach to the phenomenon of perceptual grouping by proximity was investigated. Grouping judgments of random dot patterns were made by the CODE algorithm (van Oeffelen & Vos, 1982) and several related algorithms, and these judgments were compared with subjects' grouping judgments for the same stimuli. Each algorithm predicted significantly more subject judgments than would be expected by chance. The more subjects agreed on how a given dot pattern should be grouped, the more successful was the algorithms' ability to match the judgments for that pattern. CODE predicted significantly fewer subject judgments than did some of the other algorithms, largely because of its overemphasis on the extent of interactivity among dots as they are being grouped. PMID- 8483705 TI - Mechanisms in the haptic horizontal-vertical illusion: evidence from sighted and blind subjects. AB - The haptic horizontal-vertical illusion was studied in two experiments. In Experiment 1, the illusion was relatively weak in sighted subjects and depended on stimulus size and the nature of the figure, that is, whether the pattern was an inverted-T or L shape. Experiment 2 compared early blind and late blind subjects. The illusion was present for an inverted-T figure but absent for an L figure in late blind subjects. However, the early blind subjects treated both the L and T figures as similar and showed the illusion to both. These results support the idea that visual experience may alter haptic judgments in sighted and late blind subjects. PMID- 8483706 TI - Properties of curvilinear vection. AB - Approximately linear relationships were observed between contrast, spatial frequency, temporal frequency, or velocity of stimulation and perceived velocity of curvilinear vection--that is, a visually induced self-motion in a curved path. Similarly, linear relationships were also found between the perceived degree of curvature of curvilinear vection and spatial frequency or velocity of stimulation. Since the perceived velocity of curvilinear vection varies with contrast, spatial frequency, temporal frequency, and angular velocity, and the perceived degree of curvature of curvilinear vection varies only with spatial frequency and angular velocity, peripheral vision is not sufficient for computing accurately the curvilinear component of induced self-motion in a curved path. Concurrently, it was shown that the perceived direction of curvilinear vection is not always unambiguously perceived (Sauvan & Bonnet, 1989). Consequently, it is suggested that two different types of visual processing, which involve the peripheral or the central vision, underlie the processing of curvilinear vection. PMID- 8483707 TI - Influences of closure, occlusion, and size on the perception of fragmented pictures. AB - Two experiments examined the ability to recognize a repeated figure in stimuli where only fragments of the figures were presented. Fragments were either closed or open regions presented either with or without an occluder that filled the spaces between the fragments (Experiment 1). Recognition performance was significantly better for open fragments, with or without an occluder, contrary to previous assertions that the occluder is the important factor for recognition. When stimulus size was varied, an occluder hindered recognition performance in the smallest size condition relative to unoccluded stimuli, which were equally easy to recognize across all size conditions (Experiment 2). The size results support the idea of size invariance in object naming. The difficulty in the smallest occluded condition is discussed in terms of differences in global and local processing depending on visual angle and sparsity. PMID- 8483708 TI - Event-related brain potentials reflect traces of echoic memory in humans. AB - In sequences of identical auditory stimuli, infrequent deviant stimuli elicit an event-related brain potential component called mismatch negativity (MMN). MMN is presumed to reflect the existence of a memory trace of the frequent stimulus at the moment of presentation of the infrequent stimulus. This hypothesis was tested by applying the recognition-masking paradigm of cognitive psychology. In this paradigm, a masking sound presented shortly before or after a test stimulus diminishes the recognition memory of this stimulus, the more so the shorter the interval between the test and masking stimuli. This interval was varied in the present study. It was found that the MMN amplitude strongly correlated with the subject's ability to discriminate between frequent and infrequent stimuli. This result strongly suggests that MMN provides a measure for a trace of sensory memory, and further, that with MMN, this memory can be studied without performance-related distortions. PMID- 8483709 TI - Perceived numerosity of spatiotemporal events. AB - Numerosity discrimination was examined when items were varied in space-time position rather than in space only. Observers were instructed to indicate which of two adjacent streams of visual events contained more items. The precision of numerosity discrimination of dynamic events was not remarkably different from that of static patterns. Two basic numerosity biases previously found for static dot patterns--inhibitory overestimation and satellite underestimation--were demonstrated for items distributed randomly over a spatiotemporal interval. It was also demonstrated that two streams, equated in the number and luminous energy of items, are not judged equal in their visible number if items in one of these two streams have longer duration than items in the second stream. These findings can be accounted for by the occupancy model of perceived numerosity (Allik & Tuulmets, 1991a) if it is supposed that the impact that each element has on its neighborhood is spread along both spatial and temporal coordinates. Perceived numerosity decreases with both spatial and temporal proximity between the visual items. Space and time have interchangeable effects on perceived numerosity: the amount of numerosity bias caused by the spatial proximity of items can also be produced by the properly chosen temporal proximity of items. PMID- 8483710 TI - A message to students--for all nurses. PMID- 8483711 TI - New Jersey State Nurses' Association history: what is past is prologue. PMID- 8483712 TI - Current nursing concerns--ethics arena. PMID- 8483713 TI - Practical nursing programs test catalog 1993. PMID- 8483714 TI - Community health concepts in associate degree curriculum. PMID- 8483715 TI - Educational accountability for an aging society. PMID- 8483716 TI - The prospective of long-term care educational partnerships: an essential community collaboration. PMID- 8483717 TI - Developing management skills through a preceptor-based experience in community nursing homes. PMID- 8483718 TI - Nursing education and computers: in retrospect and prospect. PMID- 8483719 TI - Innovation in the classroom: how to meet the technological challenge. PMID- 8483720 TI - Interactive videodisc technology in nursing education. PMID- 8483721 TI - The success project: a model to increase admission, retention, and graduation of minority students. PMID- 8483722 TI - Culture in curriculum: a process for integrating multicultural elements into the nursing curriculum. PMID- 8483723 TI - Prospectives: creating the future. The story of a teacher-student partnership. PMID- 8483724 TI - Caring: a meaning of competence. PMID- 8483725 TI - Teaching nursing content to the 90s learner. PMID- 8483726 TI - The curriculum revolution: implications for associate degree nursing education. PMID- 8483727 TI - Journal usage in the clinical area: a guide for nursing educators. PMID- 8483728 TI - Partnership for change: improving the medication experience. PMID- 8483729 TI - A unique approach to first semester. PMID- 8483731 TI - Grading bypass. PMID- 8483730 TI - What's your poison? PMID- 8483732 TI - Difficult choices. PMID- 8483733 TI - Capital gains. PMID- 8483734 TI - Great expectations. PMID- 8483735 TI - Lessons for the teacher. PMID- 8483736 TI - Modern studies. PMID- 8483737 TI - Systems of life. The nervous system. 7. PMID- 8483738 TI - Transfer time? PMID- 8483739 TI - Home truths. PMID- 8483740 TI - One of the family. PMID- 8483741 TI - The new game in town. PMID- 8483742 TI - Facial expressions as pain indicators. PMID- 8483743 TI - Extent of glove damage during surgery. PMID- 8483744 TI - Do women prefer single-sex GUM clinics? PMID- 8483745 TI - Intensive therapy. High-tech mix. PMID- 8483746 TI - New advice on hepatitis B. PMID- 8483747 TI - Students with HIV may be barred from training. PMID- 8483748 TI - Primary care teams for HIV/AIDS clients. PMID- 8483749 TI - Safer sex package designed to help young offenders. PMID- 8483750 TI - Testing time. PMID- 8483751 TI - Out in the cold. PMID- 8483752 TI - Getting it wrong. PMID- 8483753 TI - One step back. PMID- 8483754 TI - Saved by the pig? PMID- 8483755 TI - Transplants. Gift of life. PMID- 8483756 TI - Transplants. Tissue of progress. PMID- 8483757 TI - Transplants. Match point. PMID- 8483758 TI - Proper precautions? PMID- 8483759 TI - No room for change. PMID- 8483760 TI - Living and learning in supported housing. PMID- 8483761 TI - Prescription for change. PMID- 8483762 TI - Road to recovery. PMID- 8483763 TI - UKCC beefs up guidance on HIV-positive staff. PMID- 8483764 TI - Talking it through. PMID- 8483765 TI - Coughing in infants after thickened feeds. PMID- 8483767 TI - Quality assurance and infection control. PMID- 8483766 TI - Does counseling help hysterectomy patients? PMID- 8483768 TI - Protective instincts. PMID- 8483769 TI - Continence. Well disposed? PMID- 8483770 TI - Continence. Mix and match. PMID- 8483771 TI - Continence. A helping handle. PMID- 8483772 TI - An evaluation of the physical and functional characteristics of infant resuscitators. AB - Self-inflating resuscitators (SIRs) are commonly used to assist ventilation in the newborn. Despite their widespread use, there is limited information available on the functional and physical characteristics of SIRs. We studied five new infant bag-valve units to compare their physical characteristics, including reservoir, accumulator, and dead space volumes (VD), pressure relief mechanism (PRM), inspiratory resistance (RI), and functional mechanics including stroke volume (SV), fraction of delivered oxygen (FDO2), and cycle frequency at -5 degrees C, 20 degrees C, and 49 degrees C, using a test lung apparatus and experienced respiratory therapists. In addition, deficiencies and features that may render them less than ideal were sought. All SIRs met minimum standards for reservoir and accumulator volumes, RI (< 20 cmH2O/L/sec), SV (20-70 ml), and FDO2 (> 90%) as determined by the Canadian Standards Association (CSA) and the American Society for Testing of Materials (ASTM). However, the following deficiencies were noted: 1) MPR and Pulmanex had no PRM (ASTM requirement); 2) MPR could not cycle at -5 degrees C; 3) the VDs for Pulmanex (10 ml) and MPR (15 ml) were high; 4) the CPR connector broke during normal use, and the MPR connector frequently disconnected; 5) the Laerdal expiratory valve was incompetent; and 6) the Laerdal and CPR could be misassembled for use. Our study shows that some commercially available SIRs do not meet all CSA and ASTM standards and may not be ideal in specific clinical situations. The choice of a SIR may be dictated by the clinical situation in which its use is intended. PMID- 8483773 TI - Do not resuscitate. PMID- 8483774 TI - A five year old with a pacemaker. PMID- 8483775 TI - Elbow injury. PMID- 8483776 TI - Case 01-1993: a six-year-old girl with respiratory distress following involvement in a motor vehicle crash. PMID- 8483777 TI - Bronchodilator therapy in wheezy infants: a commentary. PMID- 8483778 TI - Pediatric emergency medicine fellowship programs. PMID- 8483779 TI - Legal concerns about the private patient in the pediatric emergency department. PMID- 8483780 TI - Examining the common dilemma of whether to order skull radiographs on asymptomatic infants with minor head injury. PMID- 8483781 TI - Emergency transport and positioning of young children who have an injury of the cervical spine. PMID- 8483782 TI - Transport stabilization times for neonatal and pediatric patients prior to interfacility transfer. AB - The stabilization times for 2863 neonatal and pediatric interfacility transports are reported. Appropriate stabilization of the sick neonate and pediatric patients prior to transfer is considered essential to reduce the adverse events that may otherwise occur during the transfer process. The median stabilization time for a neonate was 80 minutes, and it was 45 minutes for a pediatric patient. These times can be used by other transport systems to evaluate their services through quality assurance, as well as for staff and budgeting purposes. New interventions that reduce stabilization times can be evaluated with these times as a reference. PMID- 8483783 TI - Referral, admission, and discharge patterns in a pediatric emergency department in Israel. AB - The pediatric emergency department (PED) is an important component of the medical services provided by a hospital. The purpose of the study was to describe the patterns of referrals, admissions, and discharges in a PED to determine to what extent the PED is used solely as an emergency unit, as opposed to being used as a part of a set of primary care facilities. Data were recorded from 1200 patient charts, out of 19,000 visits to a PED in Israel in 1988. Variables such as age, sex, ethnicity, and distance between residence and hospital were checked. About half of the patients arrived during the morning shift. There was an inverse relationship between the distance from the patient's home to the hospital and the rate of visits to the PED. Fifty-eight percent of the total were self-referred; this rate increased to 84% during the night shift. Only one quarter of all children had additional laboratory or x-ray tests. Most of the diagnoses did not require emergency services. Eighty-one percent of the patients were discharged from the PED to their community physician. The rate of admissions was low (11%). This study shows that a large part of the PED work is actually primary care. Some of the demographic, cultural, and ethnic reasons for these patterns are reviewed. PMID- 8483784 TI - Inefficacy of intraperitoneal fluid administration in a shock model. AB - Intraperitoneal (IP) fluid administration has been previously used to treat dehydrated children. The relative ease and reported safety of this route suggests its potential utility for volume resuscitation in the acutely ill child. Previous research regarding IP fluid infusion has not examined its use in shock states. This experiment sought to examine the efficacy of an IP fluid infusion in a shock model. Ten immature swine were randomized to receive either no treatment (n = 5) or 30 ml/kg of warmed lactated Ringer's solution (n = 5) IP 20 minutes after a graded 40% hemorrhage. Mean arterial pressure (MAP), heart rate (HR), hematocrit (Hct), pH, and PCO2 were determined serially, and the experiment concluded 60 minutes after intervention. A mean of 89.5% of the administered fluid load was recovered from the peritoneal cavity, and the IP infusion had no ameliorative effect on MAP or HR. The lack of clinically significant absorption of an administered isotonic intraperitoneal fluid infusion in this model suggests that this route should not be relied upon in the critically ill child presenting in shock. PMID- 8483785 TI - Prevention of hypoxemia during lumbar puncture in infancy with preoxygenation. AB - Hypoxemia has previously been reported during lumbar puncture (LP) in infancy. The purpose of this study was to determine whether preoxygenation before the LP would reduce hypoxemia during the procedure in infants. Twenty-one infants (one to 15 weeks of age) undergoing LP for evaluation of possible sepsis were randomly assigned to the control group (12) or treatment group (9). The treatment group was preoxygenated breathing oxygen (FiO2 = 1.0) spontaneously via snug face mask for three minutes prior to being positioned for the LP. The control group spontaneously breathed room air during this interval. Oxyhemoglobin saturation was measured prior to, and continuously during, the LP with pulse oximetry. The groups were comparable in age, resting respiratory rate, baseline saturation, and duration of the procedure. The treatment group developed significantly less desaturation during the procedure than the control group (P < 0.05). We conclude that preoxygenation prior to LP prevents most of the hypoxemia resulting from the procedure in infants. PMID- 8483786 TI - Correlating infectious outcome with clinical parameters of 1130 consecutive febrile infants aged zero to eight weeks. AB - The study objectives were to characterize the infectious outcomes and associated clinical parameters of a large group of febrile young infants who received outpatient sepsis evaluation. This retrospective review of consecutive cases during a seven-year period was set in an urban pediatric emergency department. Febrile infants, aged zero to eight weeks, were the participants. All received a standard evaluation for sepsis, including complete blood count/blood culture, lumbar puncture/cerebrospinal fluid culture, and urinalysis/urine culture. Of 1130 patients, 447 (42%) were aged zero to four weeks, and 683 (58%) were aged four to eight weeks. In 96 cases (8.5%), a bacterial pathogen was isolated by culture of cerebrospinal fluid, blood, urine, or stool; 58% were aged zero to four weeks and 42% were aged four to eight weeks. The rate of positive cultures per patient age was doubled in those aged zero to four weeks (12%) compared with those aged four to eight weeks (6%). The 49 cases of invasive bacterial infections (bacterial meningitis/bacteremia) were most commonly associated with lower degrees of fever, as slightly over one half (25/49) had temperature < 39 degrees C. The most common pathogens of invasive bacterial infection were group B streptococcus and Escherichia coli, accounting for 33 of 49 cases (67%); the most common pathogens of invasive bacterial infection in older children (Haemophilus influenzae type b and Streptococcus pneumoniae) were relatively underrepresented, accounting for only five of these 49 (10%) cases. PMID- 8483787 TI - Neonatal psoas pyomyositis simulating pyarthrosis of the hip. AB - Osteomyelitis with concomitant pyarthrosis or isolated pyarthrosis heads the differential list for a newborn with limb disuse and a flexion deformity of the hip. The diagnosis of psoas abscess, a primary suppurative myositis, should additionally be entertained. Stronger consideration should be given to this clinical entity after pyarthrosis of the hip has been excluded by an arthrocentesis performed under fluoroscopy. Radiologic imaging may facilitate the diagnosis. A blood culture may yield the organism responsible for the skeletal muscle abscess, even in nontoxic patients. PMID- 8483788 TI - Penile zipper entrapment: a simple and less threatening approach using mineral oil. AB - Penile zipper entrapment, when it presents to the office or emergency department, can prove to be a challenging management problem. An easily implemented alternative approach is presented, along with a review of previously reported experience with this problem. PMID- 8483789 TI - An infant with transient intracranial hypertension associated with a febrile illness. PMID- 8483790 TI - Injuries sustained during flipping--a new fad activity. AB - This article describes a small series of injuries resulting from a new fad activity among children in Baltimore. "Flipping" involves jumping from an elevated surface and executing an aerial flip, with the intent to land upright. Because this activity takes place frequently on hard surfaces such as concrete, injuries often result. The spectrum of injuries is described and categorized, and injuries are compared with those received during similar activities, such as break dancing or skateboarding, and with playground injuries. Pediatricians and emergency physicians should be aware of the potential for injury in this activity. PMID- 8483791 TI - Pediatric cardiopulmonary resuscitation: an update based on the new American Heart Association guidelines. PMID- 8483792 TI - Synthetic peptides inhibit the interaction of von Willebrand factor-platelet membrane glycoproteins. AB - We synthesized peptides of the general formula Argn, Lysn, and (Lys-Arg)n. These agents inhibited the ristocetin-mediated binding of vWF to GPIb and the binding of asialo-vWF to platelets. This inhibitory activity was proportional to the number of lysine and/or arginine residues/molecules present. Peptides to which the sequence of Arg-Gly-Asp-Val (RGDV) had been added at the carboxy-terminus of (Lys-Arg)n, Lysn, or Argn also inhibited vWF binding. Peptides with an RGDV sequence were found to block the binding of 125I-fibrinogen to ADP-stimulated platelets. These findings indicate that the general formulae (Lys-Arg)n, Lysn, and Argn with an RGDV sequence inhibit the binding of fibrinogen to activated platelets as well as the binding of vWF to GPIb. Thus, these peptides may behave as bifunctional antiplatelet agents. PMID- 8483793 TI - Isolation of 50% of IR-CGRP content was seen in the cardiovascular tissues (e.g., heart and peripheral arteries), lungs, gastrointestinal tract (e.g., esophagus, stomach, and intestine), genitourinary tract (e.g., ureter, bladder, uterus, and penis), and in the nervous system (e.g., dorsal root and trigeminal ganglia, sciatic and trigeminal nerves, and dorsal spinal cord) in capsaicin-treated rats, in comparison with the control rat tissues (p < 0.01). These findings are compatible with the known involvement of capsaicin of the unmyelinated sensory C and A delta fibers and hence their distribution in the nervous system and other organs. Plasma IR-CGRP levels were also significantly lower in the capsaicin-treated rats throughout their life span (p < 0.001), suggesting that, at least in part, circulating CGRP is derived from the nervous system. RP-HPLC confirmed the identity of CGRP in both tissue and plasma extracts. PMID- 8483804 TI - Different effects of CCK antagonists on gastric-acid response to CCK and pentagastrin. AB - The role of CCK receptor subtypes in peptide-stimulated acid secretion was assessed in six unanesthetized rats. The CCK-stimulated acid secretion was not blocked by L-365,260, a CCKB/gastrin receptor antagonist, and was significantly increased by devazepide, a CCKA receptor antagonist, given alone or together with L-365,260. L-365,260, but not devazepide, blocked pentagastrin-stimulated acid secretion, and, when given together, devazepide abolished the effect of L 365,260. We conclude: 1) pentagastrin stimulates acid secretion through a gastrin type receptor, but CCK may not, and 2) pentagastrin and CCK can stimulate acid secretion despite simultaneous blockade of CCKB/gastrin and CCKA receptors. PMID- 8483805 TI - Modulatory effects of vasopressin on glucose and protein metabolism during food restriction stress. AB - Plasma levels of glucose and urea nitrogen were compared in vasopressin containing (LE) and vasopressin-deficient (DI) rats under ad lib and food restricted conditions. In the ad lib situation, DI and LE rats had similar levels of glucose and urea nitrogen. Variations in this pattern were observed under food restricted conditions. The DI animals exhibited lower levels of glucose and higher levels of urea nitrogen than their LE counterparts. During food restriction, the glucose levels of LE animals were not different from that observed under ad lib conditions. A significant decrease, however, was observed in the glucose levels in DI animals during food restriction. Urea nitrogen levels in LE animals decreased during food restriction as compared to the ad lib situation, whereas urea nitrogen levels of DI animals increased during food restriction. These observations indicate that vasopressin has a modulatory role on glucose and protein metabolism during the stress of food restriction. PMID- 8483806 TI - Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells. AB - Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of cultured rat aorta- and vena cava-derived SMC. Both cell types displayed high-affinity NPY binding sites with displacement characteristics of [Pro34]NPY > NPY(13-36) > NPY(18-36) in aorta and [Pro34]NPY = NPY(13-36) = NPY(18-36) in the vena cava. Incubation with NPY (50-1000 nM) for 48 h increased by up to twofold cell number and [3H]-thymidine incorporation in both cell types (aortic more sensitive to NPY than venous). Following incubation with NPY, the disappearance of NPY immunoreactivity (-IR) from media was markedly delayed in the presence of SMC, and cell content of NPY-IR increased in a dose-dependent manner, indicating that SMC either diminish degradation of the peptide (possibly by internalization) or secrete endogenous NPY (or both). Structure-activity relationship studies with NPY(18-36) indicated involvement of Y1 receptors in mitogenesis. Thus, NPY has a mitogenic effect (probably mediated by Y1 receptors) and, therefore, may be a sympathetic trophic factor involved in vascular hypertrophy. PMID- 8483807 TI - Parathyroid hormone-induced dopamine turnover in the rat medial basal hypothalamus. AB - The parathyroid hormone (PTH) gene is expressed and translated in the rat hypothalamus, and the possibility that PTH may modulate neural activity was therefore examined in anesthetized rats. Intracerebroventricular (ICV) injections of 1.0 or 10.0 micrograms rat, human, or bovine PTH(1-34) was followed 60 min later by increased concentrations of DOPAC (dihydroxyacetic acid) and the DOPAC:dopamine (DA) ratio in the medial basal hypothalamus (MBH), but not in other (brainstem, cerebral cortex, cerebellum) regions of the brain. Tissue concentrations of norepinephrine and serotonin were unchanged by ICV PTH administration, although MBH concentrations of 5-hydroxyindolacetic acid (5-HIAA) were increased following PTH administration. An increase in MBH DA turnover (as indicated by an increased DOPAC:DA ratio) was also induced by the ICV injection of 10 micrograms PTH-related protein [PTHrP(1-34)]. Pretreatment with the receptor antagonists PTH(7-34) or PTHrP(7-34) completely blocked the subsequent DOPAC response to ICV PTH or PTHrP, respectively. The DOPAC concentrations in hypothalamic extracellular fluid (ECF), sampled by microdialysis, were also increased within 20 min of PTH(1-34) perfusion, in the absence of changes in the ECF concentrations of 5-HIAA. These results demonstrate that PTH and PTH-like peptides specifically increase DA turnover in the rat MBH and suggest novel roles for these hormones in neural regulation. PMID- 8483808 TI - Testosterone increases TRH biosynthesis in epididymis but not heart of zinc deficient rats. AB - Enzymes responsible for the posttranslational processing of precursor proteins to form alpha-amidated peptide hormones require the availability of several cofactors, including zinc, copper, and ascorbic acid. For this reason, we studied the effects of 6 weeks of a zinc-deficient diet (ZD1; 1 microgram zinc per g diet), pair-feeding (PF), and marginal zinc deficiency (ZD6; 6 micrograms zinc per g diet) compared to a control diet (36 micrograms/g zinc) on the conversion of prepro-TRH to TRH in epididymides, testes, prostate, pancreas, and heart of young adult, male Sprague-Dawley rats. In the epididymis, severe zinc deficiency (ZD1 diet) reduced TRH and TRH-like peptides to undetectable levels. In ZD6 animals, TRH was selectively inhibited 80%, while pair-feeding increased all of these peptide levels compared to controls. A similar effect of zinc deficiency on the TRH precursor peptides was observed. A quantitative loss of TRH from the testes of ZD1 was also observed. Zinc deficiency results in a substantial reduction in body weight and testosterone production in male rats. Exogenous testosterone (T) supplementation of ZD1 rats resulted in a selective increase in the TRH concentration of the epididymis but not of the heart. The change in steady-state levels of TRH precursor peptides in the hearts of the ZD1+T rats was consistent with a reduction in the activity of the zinc-dependent carboxypeptidase H enzyme. We conclude that severe zinc deficiency inhibits TRH biosynthesis in reproductive tissues of the male rat due to the combined effects of hypogonadism and inhibition of the zinc-dependent carboxypeptidase H. PMID- 8483809 TI - Preparation of N epsilon B28-monoazidobenzoyl insulin-like growth factor I and photoaffinity labeling of insulin-like growth factor I receptor. AB - Recombinant human insulin-like growth factor I (hIGF-I) was reacted with azidobenzoyl hydroxysuccinimide to produce a mixture of photoactive hIGF-I derivatives. The mixture was purified by reversed-phase HPLC to yield three mono substituted azidobenzoyl hIGF-Is. One of the derivatives was identified by amino acid sequencing as N epsilon B28-monoazidobenzoyl hIGF-I. This derivative was indistinguishable from native hIGF-I when bioassayed in Rat-1 fibroblasts. A 120 kDa band, the alpha subunit of the IGF-I receptor, was specifically labeled in Rat-1 plasma membranes by this photoprobe. The labeling of this band was reduced by hIGF-I at 1 nM and completely abolished by hIGF-I, but not insulin, at 100 nM, indicating the specificity of the photolabeling of the IGF-I receptor by this fully active IGF-I photoprobe. PMID- 8483810 TI - The flp-1 propeptide is processed into multiple, highly similar FMRFamide-like peptides in Caenorhabditis elegans. AB - Previously, we described a gene, flp-1, that encodes seven FMRFamide-like peptides from two alternatively spliced transcripts in the nematode Caenorhabditis elegans. To determine whether all or a subset of the predicted peptides coded for by flp-1 are produced in vivo, we undertook the isolation of FMRFamide-like peptides from C. elegans. Six FLRFamide-containing peptides, all contained within the putative translation products of the flp-1 gene, were isolated from extracts of mixed stage animals. By quantitative PCR analysis of RNA from mixed stage animals, we found that the shorter transcript of flp-1 has a higher level of expression than the longer transcript. PMID- 8483811 TI - Bombesin acts in the brain to decrease gastric vagal efferent discharge in rats. AB - The central nervous system action of bombesin to influence basal gastric vagal efferent discharge (GVED) was investigated in urethane-anesthetized rats. Bombesin (62, 620, and 6200 pmol) injected intracisternally (IC) decreased GVED to 78 +/- 10%, 50 +/- 4%, and 43 +/- 3% of preinjection levels, respectively. Bombesin (620 pmol) injected IV also reduced GVED to 36 +/- 6%. Pretreatment with bombesin monoclonal antibody 2A11 completely prevented the decrease in GVED induced by bombesin (620 pmol) given IV but not IC. These data indicate that both IC and IV injections of bombesin decrease basal GVED, and that the inhibitory effect of IC injection represents a central nervous system-mediated action. PMID- 8483812 TI - Peptidases and smooth muscle cell angiotensin II receptor pharmacology. AB - Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [125I][Sar1Ile8]AII ([125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [125I]SI-AII binding, and their rank order of potencies, and Ki values (nM) were: AII (3.7) > AI (32.5) > or = AIII (54.0), which differed from that observed for rat adrenal cortex: AII (0.85) > AIII (3.3) >> AI (100). Similar results were observed for RASM membranes in the presence of guanine nucleotides, and for intact cells in the absence or presence of an internalization inhibitor. Lowering the incubation temperature from 37 degrees C to 4 degrees C, or inclusion of PMSF (1 mM), and preparing membranes in the presence of EGTA (1 mM) altered the rank order of potencies and Ki values (nM) of the angiotensin peptides to: AII (1.1) > AIII (7.0) >> AI (144). [125I]Angiotensin I was metabolized completely over the course of 90 min to small ( GQQHHLGGAKQAGDV (G15). The RGES peptide had no inhibitory activity. The inhibitory effects of the peptides were synergistic when fibrinogen binding was measured in the mixture of the RGD peptide and the gamma chain peptide. By contrast, the inhibitory effect was additive when the binding was measured in the presence of the RGDS peptide and the RGDF peptide. Thrombin-induced platelet aggregation was also inhibited by these synthetic peptides. The order of potency was the same as that of the inhibition binding assay. These results provide evidence that the RGD sequences present at two different sites in the alpha chain and the gamma chain sequence inhibit fibrinogen binding to the GPIIb/IIIa complex, are mutually exclusive, and are in close spatial proximity in the folded molecule. We conclude that the presence of the RGD sequence and the gamma chain sequence involved in fibrinogen binding domains increases the affinity of fibrinogen to activated platelets. PMID- 8483814 TI - Effects of age and hyperlipidemia on rabbit coronary responses to neuropeptide Y and the interaction with norepinephrine. AB - In coronary arteries from New Zealand White (NZW) rabbits up to 12 months of age, both direct vasoconstriction to neuropeptide Y (NPY) and inhibition of relaxation to norepinephrine (NE) by NPY were age dependent (p < 0.02 and p < 0.05, respectively); maximal relaxation to NE was unaffected. NPY had no significant effect on arteries from NZW rabbits at 4 months of age, while vessels from Watanabe Hereditable Hyperlipidaemic (WHHL) rabbits showed enhanced direct (p < 0.001) and indirect effects of NPY (p < 0.02). We conclude that the postsynaptic vasoconstrictor effects of NPY on the epicardial coronary artery increase with age and the presence of hyperlipidemia. PMID- 8483815 TI - Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity in pheochromocytomas. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel hypothalamic peptide consisting of 38 amino acids [PACAP(1-38)] with a potent stimulatory action on adenylate cyclase in rat pituitary. The presence of immunoreactive (IR-) PACAP in the tumor tissue of pheochromocytomas was studied by radioimmunoassay and immunocytochemistry. The antibody to PACAP was raised in a rabbit injected with a peptide containing amino acids 28-38 of PACAP. This antibody showed no significant cross-reactivity with either PACAP(1-27) or vasoactive intestinal polypeptide. The tumor tissue concentrations of IR-PACAP(1 38) were 0.5-57.5 pmol/g wet weight (n = 13) (24.5 +/- 22.4 pmol/g wet weight, mean +/- SD), while those in the normal adrenal glands were 3.58 +/- 2.02 pmol/g wet weight (n = 7) and those in the adrenal cortical tumors were 5.58 +/- 2.02 pmol/g wet weight (n = 6). The IR-PACAP(1-38) concentrations in 7 out of 13 pheochromocytomas exceeded 18 pmol/g wet weight. Sephadex G-50 column chromatography revealed that the IR-PACAP(1-38) in extracts of pheochromocytomas eluted in both the positions of PACAP(1-38) and a larger molecular weight. Reverse-phase high performance liquid chromatography of the tumor extracts revealed a peak in the position of PACAP(1-38) and at least four other peaks. Immunocytochemistry of pheochromocytomas showed numerous immunoreactive cells. The immunostaining was abolished by absorption of the antiserum with synthetic PACAP(1-38). These findings indicate that multiple forms of IR-PACAP(1-38) are present in pheochromocytomas. PMID- 8483816 TI - Growth regulatory properties of endothelins. AB - Endothelins are produced by endothelial and epithelial cells, macrophages, fibroblasts, and many other types of cells. Their receptors are present in numerous cells, including smooth muscle cells, myocytes, and fibroblasts. Evidence now suggests that the three isoforms of endothelins (ET-1 and the other two related isopeptides, ET-2 and ET-3) regulate growth in several of these cells. Endothelin-1 influences DNA synthesis, the expression of protooncogenes, cell proliferation, and hypertrophy. The participation of ET in mitogenesis involves activation of multiple transduction pathways, such as the production of second messengers, the release of intracellular pools of calcium, and influx of extracellular calcium. Moreover, ET-1 acts in synergism with various factors, such as EGF, PDGF, bFGF, TGFs, insulin, etc., to potentiate cellular transformation or replication. Several of these factors may in turn stimulate the synthesis and/or the release of endothelins. The production and release of endothelins are also increased in acute and chronic pathological processes, e.g., atherosclerosis, postangioplastic restenosis, hypertension, and carcinogenesis. It is postulated that endothelins act in a paracrine/autocrine manner in growth regulation and play an important role mediating vascular remodeling in some cardiovascular diseases. The present review analyses the implication of endothelins (ET-1, -2, and -3) in physiopathology related to their growth regulatory properties. PMID- 8483817 TI - Atriopeptin III degradation by endopeptidase 24.11: the Cys-Phe bond is not the preferential cleavage site. AB - Incubation of rANP(5-28)--also called atriopeptin III (AP III)--with purified endopeptidase 24.11 led preferentially to the production of Phe-Arg-Tyr, while other products of minor importance were detected. One of these was identified as rANP(5-25) (atriopeptin I) (AP I). This hydrolysis pattern of endopeptidase 24.11 towards AP III differs from the known favored site of cleavage at the Cys7-Phe8 bond of rANP(1-28). Moreover, by comparison with rANP(1-28), the degradation rate of AP III was slower. These data suggest that N-terminal peptide truncation results in conformational and/or charge modifications leading to a different positioning of the peptide in the endopeptidase 24.11 active site. In most hypothalamic nuclei of the rat brain known to contain AP III and endopeptidase 24.11, the preferential Ser25-Phe26 bond hydrolysis, although supposed to be responsible for a reduced degradation rate, might represent an effective enzymatic pathway of catabolism for AP III. PMID- 8483818 TI - Aortic valve stenosis. Management in children and adults. AB - Aortic valve stenosis may be congenital or acquired. Medical management includes advice to avoid heavy physical effort, prevention of infective endocarditis, use of digitalis and diuretics for cardiac failure, and preservation of atrial systole. When operation is necessary, open aortic valve commissurotomy is preferred in children and replacement of the valve is preferred in adults. Women of childbearing age should use conventional barrier contraceptives, and those with severe stenosis should have valve replacement before becoming pregnant. Aortic valvuloplasty, particularly in adults, is only of temporary benefit. PMID- 8483819 TI - Making sense of hypothyroidism. An approach to testing and treatment. AB - Development of the newer, sensitive assay for thyrotropin (thyroid-stimulating hormone [TSH]) has simplified the diagnosis and management of hypothyroidism. Serum free thyroxine (T4) levels measured by analogue techniques or free T4 index may be used in conjunction with TSH test results to confirm the diagnosis. Treatment consists of daily doses of levothyroxine sodium (Levothroid, Levoxine, Synthroid), which are increased slowly to achieve an optimal dose. Close monitoring with TSH assay is important to ensure adequate treatment. In euthyroid sick syndrome, results of thyroid function tests are abnormal in patients with nonthyroidal illness; treatment is indicated if symptoms of hypothyroidism are present. Patients with subclinical hypothyroidism also may benefit from treatment. PMID- 8483820 TI - Milk-alkali syndrome. A consequence of chronic antacid abuse. AB - The case described here illustrates the need to consider milk-alkali syndrome in the differential diagnosis of hypercalcemia, even in this age of histamine2 blockers and mucosal protectors. Thorough history taking and gastrointestinal workup help rule out alternative causes of hypercalcemia, such as cancer, hyperparathyroidism, and other metabolic and endocrine diseases. Milk-alkali syndrome is managed by administration of saline solution and loop diuretics and avoidance of thiazide diuretics. Patient education regarding the hazards of abusing calcium-containing antacids is essential. PMID- 8483821 TI - Detecting the presence and cause of pulmonary edema. AB - Prompt recognition of pulmonary edema is important to avoid life-threatening complications. Chest radiography and other tests are key to establishing the diagnosis and distinguishing between the two types of pulmonary edema- cardiogenic and noncardiogenic. Dr Colice discusses the mechanisms that lead to pulmonary edema, the various diagnostic methods, prognosis, and management. PMID- 8483822 TI - Common bacterial skin infections. Diagnostic clues and therapeutic options. AB - Prompt, accurate characterization of skin infections can help avoid serious, more invasive complications. With appropriate empirical therapy, treatment failure can be prevented. The authors of this article discuss several common skin infections, including bite wound infections, and recommend various drug regimens to consider when planning initial therapy. PMID- 8483824 TI - Health plan made in secret by folks who don't know they don't know! PMID- 8483823 TI - Gait disorders in the elderly. Distinguishing between normal and dysfunctional gaits. AB - Normal gaits in the elderly population vary widely. Characteristics of normal and abnormal gaits often overlap, making diagnosis of ambulation disorders difficult in some patients. Abnormal gaits are usually caused by musculoskeletal and/or neurologic abnormalities, which can be readily identified in the clinical setting. Prompt diagnosis and appropriate treatment may save an elderly patient from immobility, fall-related injury, loneliness, and depression. PMID- 8483825 TI - Future of healthcare. PMID- 8483826 TI - Mitral valve prolapse. Avoiding complications of a progressive disease. AB - Mitral valve prolapse is a common disorder, but it carries low morbidity and mortality. Patients require close follow-up, however, to prevent development of serious complications. In addition, patients with thickened mitral valve leaflets or mitral regurgitation require antibiotic prophylaxis against infective endocarditis. Family members of patients with primary mitral valve prolapse should be screened for the disease, because it often is asymptomatic. PMID- 8483827 TI - Aortic regurgitation. Identifying and treating acute and chronic disease. AB - Aortic regurgitation is a serious disorder that can challenge the best clinicians in terms of both diagnosis and management. The chronic form requires valve replacement when patients have symptoms or show evidence of left ventricular dysfunction. The acute form requires urgent aortic valve replacement. In all cases, medical management is only a temporizing procedure that can potentially mask the progression of left ventricular dysfunction. Endocarditis prophylaxis for indicated procedures is mandatory for all patients. PMID- 8483828 TI - Rheumatic mitral stenosis. On the rise again. AB - Rheumatic mitral stenosis remains an important cause of exertional dyspnea, pulmonary congestion, atrial fibrillation, and stroke. Detection rests on careful auscultatory examination and detailed review of chest films. Diagnosis is confirmed by echocardiographic examination; cardiac catheterization is important in symptomatic patients to evaluate the severity of stenosis and associated lesions. Treatment of pulmonary congestion and control of heart rate in patients with atrial fibrillation remain major medical goals. Percutaneous balloon commissurotomy is preferred for most patients with predominant mitral stenosis and for those with contraindications to valve replacement. Implantation of a prosthetic valve is best for patients with significant mitral regurgitation, multivalve disease, associated coronary artery disease that requires bypass, or mitral valve deformity too severe to allow adequate balloon commissurotomy. PMID- 8483829 TI - Strategies for indirect computer-aided drug design. AB - This review is intended to describe some of the methods and procedures used for computer-aided drug design when the structure of the macromolecular target is unknown, as is the case for CNS active drugs. Strategies and methods used in computer-aided design of drugs in such instances must be "indirect," i.e., focusing on the characterization of the ligands themselves. This situation is different from one in which the three-dimensional structure of the macromolecular target for a drug is known, for example, for drugs that are enzyme inhibitors, allowing "direct" characterization of ligand-receptor interactions. Two qualitatively different "indirect" approaches are described here. One, called 2D QSAR, is briefly reviewed. It is based on delineating regression relationships between a specified biological end point and properties of the compounds eliciting it. The other, based on pharmacophore development, constitutes the main part of this review. Several levels of pharmacophore development are described, which differ in the extent to which they encompass fundamental molecular properties that are determinants of receptor recognition and activation. The strengths and limitations of each procedure are discussed and illustrated by examples. Two methods for obtaining model receptor structures are then briefly described. Both rely on the prior success of the indirect methods in obtaining ligand properties that modulate receptor recognition and activation. These emerging capabilities have the potential to bridge the gap between indirect and direct methods of drug design, since, if successful, the design process can continue in a direct mode using explicit characterization of drug-receptor interactions. Strategies for hypothesis validation and use of hypothesis for drug design and discovery are also briefly reviewed. The final sections of this review describe specific computational tools such as molecular mechanics and quantum mechanical methods used to characterize and identify relevant molecular properties and indicate some areas for future development of computational chemistry methods that could increase its effectiveness in the design of novel drugs. PMID- 8483830 TI - Controlled delivery systems for proteins using polyanhydride microspheres. AB - A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of different molecular sizes--lysozyme, trypsin, heparinase, ovalbumin, albumin, and immunoglobulin--were prepared by a solvent evaporation method using a double emulsion. The microspheres containing proteins were spherical, with diameters of 50-125 microns, and encapsulated more than 80% of the protein, irrespective of the protein used. Enzymatic activity studies showed that encapsulation of enzymes inside polyanhydride microspheres can protect them from activity loss. When not placed inside polyanhydride microspheres, trypsin lost 80% of its activity in solution at 37 degrees C at pH 7.4 in 12 hr, whereas inside the polyanhydride microspheres the activity loss was less than 10% under these conditions. About 47% of the enzymatic activity of heparinase encapsulated in the microspheres was lost at 37 degrees C in 24 hr, while in solution it lost over 90% of its activity. The protein-loaded microspheres displayed near-zero-order erosion kinetics over 5 days as judged by the release of sebacic acid (SA) from the microspheres. The microspheres degraded to form SA and FAD monomers. All proteins were released at a near-constant rate without any large initial burst, irrespective of polymer molecular weight and protein loading. The period of protein release was longer than that of SA and continued protein release was observed even after the microsphere matrix had completely degraded. Differential scanning calorimetric studies demonstrated an interaction between protein and the FAD monomers produced with microsphere degradation. It is likely that the protein interaction with FAD monomers permits formation of water-insoluble protein aggregates which slowly dissolve and diffuse out of the matrix, leading to delayed protein release. For trypsin-loaded microspheres, trypsin lost 40% of its activity during microsphere preparation. Activity studies demonstrated that the sonication process was primarily responsible for activity loss. A reduction in the period of ultrasound exposure decreased the loss of protein activity to around 20%. PMID- 8483831 TI - A new method for estimating dermal absorption from chemical exposure. 1. General approach. AB - To evaluate systemic chemical exposure from dermal absorption, one must know the mass of chemical absorbed including the portion that has entered the skin but not yet entered the body's interior system. Algebraic equations are presented for estimating dermal absorption including the effects of exposure time and chemical nature of the compound, in particular lipophilicity and molecular weight. The proposed equations account for larger absorption rates during the initial exposure period as well as the hydrophilic barrier which the viable epidermis presents to lipophilic chemicals. These algebraic expressions are shown to represent adequately the exact solution of the unsteady-state diffusion equations for a two-membrane composite. Finally, procedures are proposed for estimating a priori the required physicochemical data when experimental values are not available. Specifically, the Potts and Guy permeability correlation is split into parts separately representing stratum corneum partitioning and diffusivity. PMID- 8483832 TI - Immunotargeting of liposomes containing lipophilic antitumor prodrugs. AB - Potential therapeutic applications of recently developed liposomes with a reduced affinity to the reticuloendothelial systems and a prolonged circulation time as targeting systems for lipophilic prodrugs were examined. In these studies, liposomes composed of phosphatidylcholine and cholesterol, additionally containing monosialoganglioside (GM1) or polyethylene glycol conjugated to phosphatidylethanolamine (PEG-PE), were used. Three antitumor lipophilic prodrugs, N-trifluoroacetyl-adriamycin-14-valerate (AD32), araC-diphosphate diglyceride (araCdPdG), and 3',5'-o-dipalmitoyl-5-fluoro-2'-deoxyuridine (dpFUdR), were used to examine the effect of lipophilic prodrug incorporation into long-circulating liposomes and immunoliposomes on their biodistribution in mouse. Biodistribution studies with antibody-free liposomes containing lipophilic prodrugs showed that the activities of GM1 or PEG2000-PE in prolonging the circulation time of liposomes appeared to be preserved in the presence of each of the three lipophilic prodrugs at a drug/lipid molar ratio of 3:97. The effect of lipophilic prodrug incorporation on target binding of immunoliposomes was then examined using a mouse model. Incorporation of AD232 or dpFUdR into immunoliposomes, directed to the normal endothelium, did not affect the targetability of immunoliposomes, suggesting a potential effectiveness of these lipophilic prodrug-containing immunoliposomes in therapy for lung tumors. On the contrary, incorporation of araCdPdG resulted in significantly reduced target binding of immunoliposomes by yet unknown mechanism(s). PMID- 8483833 TI - Synthesis and testing of new antileukemic Schiff bases of N-hydroxy-N' aminoguanidine against CCRF-CEM/0 human leukemia cells in vitro and synergism studies with cytarabine (Ara-C). AB - A series of eight new N-hydroxy-N'-aminoguanidine (HAG) Schiff bases [ArCH = NNHC(= NH)NHOH.tosylate] was synthesized as potential antitumor agents through the inhibition of the enzyme ribonucleotide reductase (EC 1.17.4.1). Five of the HAG derivatives (LK02 through LK06) were designed to contain an orthohydroxy group on the phenyl ring of ArCH = to increase the stability of the Schiff base formed. In addition, two compounds with a substituted quinoline [LK10; ArCH = (4 hydroxy-7-trifluoromethylquinolin-3-yl)methylene] or isoquinoline (LK11; ArCH = (5-nitroisoquinolin-1-yl)methylene] moiety were synthesized through multiple-step reactions involving reduction and/or oxidation. The IC50 values of the newly synthesized HAG Schiff bases were determined against human leukemic CCRF-CEM/0 cells in culture. The IC50 values of two previously reported HAG derivatives [ATL25; ArCH = (5-nitro-isoquinolin-1-yl)methylene] and [LW02; ArCH = 2-hydroxy-3 allyl-benzylidene)] were also determined for the first time against CCRF-CEM/0 cells. Among the compounds tested, LK11 was found to be the most potent (IC50, 2.95 +/- 0.1 microM) and the 4-methoxy-2-hydroxyphenyl derivative (LK02) to be the least potent (IC50, 121 +/- 16 microM). LK11 was about 15-fold more potent against CCRF-CEM/0 cells compared to the parent compound hydroxyguanidine sulfate (IC50, 46 +/- 7.1 microM) and was about 32 times more potent than LK10 (IC50, 97.6 +/- 0.9 microM). LK11 in combination was incubated in sequence with cytarabine (ara-C) at various molar ratios against CCRF-CEM/0 cells for 48 hr. The results were analyzed using both the isobologram and the median-effect methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483834 TI - Aqueous ethylcellulose dispersion of ethylcellulose. I. Evaluation of coating process variables. AB - Formulation and process variables play an important role in the film-forming properties of coating polymers. Three selected independent coating process variables, namely, percent solids content in the coating polymeric dispersion, inlet-air temperature, and spray rate of the polymeric dispersion, were investigated in this study to determine their effect on the performance characteristics of tablets coated with a plasticized aqueous ethylcellulose dispersion (Sure-lease) in a fluid-bed equipment. Response surface methodology (RSM) was utilized to study the complex relationship between these process variables and selected response variables. Three response variables were considered, namely, rate of drug release from the "untreated" coated tablets and the "thermal-treated" coated tablets and microindentation hardness of the untreated coated tablets. A 12-point factorial experimental design was utilized, and three-dimensional (3-D) response surface plots were generated using a second order polynomial model. The model provided information needed to predict optimal process conditions. Drug release from the coated tablets followed zero-order kinetics. Inlet-air temperature was found to be the most critical process variable for all the three response variables studied. A correlation was observed between the drug release rate and the microindentation hardness of the applied polymeric coat in the case of untreated coated tablets. The 3-D response surface plots indicated that lower rates of drug release from the coated tablets may be obtained by using high inlet-air temperature and low spray rate of the polymeric dispersion during coating. PMID- 8483835 TI - A method for the early evaluation of the effects of storage and additives on the stability of parenteral fat emulsions. AB - The combination of sedimentation field-flow fractionation (SedFFF) and photon correlation spectroscopy (PCS) is shown to provide a detailed record of the droplet sizes present in fat emulsions commonly used in parenteral nutrition. The technique presented has been used to record size distribution data for a particular emulsion (Liposyn-II), demonstrating its high stability and lot-to-lot uniformity. The technique is also able to demonstrate how additions of small amounts of electrolytes [0.45% (w/v) NaCl, 0.05% (w/v) CaCl2] tend to destabilize the emulsion, suggesting some caution in the use of total parenteral nutrition (TPN) mixtures. In contrast, a 1:1 mixture with human serum caused no sign of instability in the Liposyn-II. Using the emulsion as a carrier for lipophilic drugs necessitates adding solutions of the drug in nonaqueous solvents, such as DMSO (dimethyl sulfoxide). This solvent's destabilizing effect results in a droplet coalescence that becomes severe after 3-5 days following a 10% (v/v) addition, while a 5% (v/v) addition reaches the same level of coalescence in 10 days. PMID- 8483836 TI - The influence of thermal treatment on the physical-mechanical and dissolution properties of tablets containing poly(DL-lactic acid). AB - Five molecular weight grades of poly(DL-lactic acid) (PLA) were incorporated as organic and aqueous pseudolatex binders into matrix tablet formulations containing microcrystalline cellulose and the model drug theophylline. The tablets were thermally treated to temperatures above and below the glass transition temperature (Tg) of the PLA. The results of the dissolution studies showed that thermally treating the tablets to temperatures above the Tg of the PLA significantly retarded the matrix drug release compared to tablets which were not thermally treated. The retardation in drug release could be attributed to a stronger compact and a more efficient redistribution of polymer throughout the tablet matrix, based on fundamental principles of annealing. In addition, results from tablet index testing supported the dissolution results. The bonding index of the compact formulations increased after thermal treatment above the Tg of the PLA. Gel permeation chromatography and differential scanning calorimetry studies demonstrated that thermal treatment had no significant effect on the molecular weight and the glass transition temperature of (PLA) alone and in combination with other components of the tablet formulation. PMID- 8483837 TI - Uptake of phosphatidylserine liposomes by rat Peyer's patches following intraluminal administration. AB - Uptake of the nonabsorbable marker 6-carboxyfluorescein was investigated both free and encapsulated in liposomes as a function of their surface charge and hydrodynamic diameter in rat Peyer's patch and nonpatch tissue. Significant uptake of the marker occurred only when encapsulated in liposomes consisting of at least 25 mol% phosphatidylserine and was highest in Peyer's patches. 6 Carboxyfluorescein encapsulated in liposomes equal to or greater than 374 nm was preferentially taken up by Peyer's patches. There was a trend to higher uptake in lower intestinal segments. These findings were supported by fluorescence microscopic observations. Uptake by Peyer's patches was specific for negatively charged liposomes as judged from competition studies. PMID- 8483838 TI - In vitro nasal transport across ovine mucosa: effects of ammonium glycyrrhizinate on electrical properties and permeability of growth hormone releasing peptide, mannitol, and lucifer yellow. AB - Transport of growth hormone releasing peptide across ovine nasal mucosa in the absence or presence of ammonium glycyrrhizinate (AMGZ) was studied in vitro. Ovine nasal mucosa was stripped from underlying cartilage and mounted in Ussing chambers. Transepithelial conductance (Gt) and short-circuit current (Isc) were monitored during experiments to assess tissue viability and integrity. Radiolabeled mannitol (Man; MW 182) and growth hormone releasing peptide (GHRP, SK&F 110679; MW 873) were employed to measure transport rates across the epithelium, and fluorescence spectroscopy was employed to measure rates of lucifer yellow (LY; MW 521) transport. Effects of AMGZ on ovine nasal mucosal viability and transport were determined from changes in electrical properties of fluxes of [3H]GHRP, [3H]Man, and LY. Results demonstrate that electrical properties of ovine nasal mucosa are stable over the time course of the experiments (Gt = 8.3 +/- 0.5 mS/cm2 and Isc = 3.7 +/- 0.2 microEq/hr.cm2; n = 21). Man fluxes were comparable in the mucosal (m)-to-serosal (s) and s-to-m directions [0.10 +/- 0.01 (n = 17) and 0.10 +/- 0.01 (n = 4) %/hr.cm2, respectively]. Transport of GHRP and LY in the m-s direction was similar to that of Man [0.08 +/- 0.01 (n = 11) and 0.09 +/- 0.01 (n = 3) %/hr.cm2, respectively]. GHRP flux was equivalent in the m-s and s-m directions. GHRP did not significantly alter ion transport processes as indicated by the lack of any change in Gt or Isc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483839 TI - Development of activity assays for high-volume evaluation of human immunodeficiency virus (HIV) protease inhibitors in rat serum: results with ditekiren. AB - We showed previously that a commercially available synthetic tetradecapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, produces authentic angiotensin I (Ang I) upon incubation with the HIV-1 protease (S. K. Sharma et al., Anal. Biochem. 198:363, 1991). Therefore, we developed an Ang-I based activity assay for HIV protease inhibitors based on the technology developed earlier (M. J. Ruwart et al., Pharm. Res. 7:407, 1990; S. K. Sharma et al., Anal. Biochem. 186:24, 1990) for tracking renin inhibitors in rat sera. Ditekiren was either extracted from sera with ethyl acetate or assayed after the interfering substances in sera were precipitated with acetonitrile. Purified recombinant HIV 1 protease was added to extracted rat serum and the enzymatic reaction was initiated in the presence of the tetradecapeptide substrate. The inhibition of Ang I production was measured by a commercially available RIA kit. The cleanup methodology also enabled a commercially available Proteinase Scintillation Proximity Assay (SPA, Amersham) to quantify ditekiren in rat serum through the addition of recombinant HIV-1 protease and cleavage of substrate from SPA beads. Results were confirmed by HPLC or by the renin assay for ditekiren, which inhibits both aspartyl proteases. These technologies should prove useful for assessing serum levels of HIV protease inhibitors in rat. PMID- 8483840 TI - Pharmacokinetics of recombinant human interferon-beta ser in healthy volunteers and its effect on serum neopterin. AB - The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcutaneous (sc) doses. Blood samples collected after the iv, first sc, and last sc doses and prior to each sc dose were assayed for interferon antiviral activity and the interferon-inducible marker neopterin. Following iv administration, serum interferon concentrations generally declined biexponentially, with a mean serum clearance of 0.76 +/- 0.28 L/hr-kg, a mean steady-state volume of distribution of 2.88 +/- 1.81 L/kg, and a mean terminal half-life of 4.29 +/- 2.29 hr as determined by noncompartmental analysis. Following sc administration, absorption of rIFN-beta ser was prolonged, with serum concentrations generally below 100 IU/mL. No accumulation of rIFN-beta ser in serum was noted after eight daily sc injections. In contrast, serum neopterin levels did not increase above baseline levels until 12 hr after iv dosing and 24 hr after sc dosing. The mean increase in serum neopterin at 24 hr post iv injection was significantly greater than that at 24 hr post sc dosing. PMID- 8483841 TI - Physicochemical stability of phenobarbital polymorphs at various levels of humidity and temperature. AB - The physicochemical stability of six phenobarbital modifications [forms A, B, C (monohydrate), D (dioxane solvate), E (hemihydrate), and F] at various levels of humidity and temperature were measured using X-ray diffractometry and differential scanning calorimetry. Form D was identified as a new crystalline form (dioxane solvate). Polymorphic transformations of the modifications were investigated by the Kissinger method under nonisothermal conditions. Change of polymorphic content of phenobarbital modifications under various humidity levels at 45 degrees C was evaluated by X-ray powder diffraction. The polymorphic stability under isothermal conditions was estimated kinetically, based upon the Jander equation. Forms A, B, and F were stable at 0 and 75% RH and 45 degrees C for 3 months. On the contrary, forms C, D, and E transformed during storage. The transformation rates of form D were larger than that of forms C and E. PMID- 8483842 TI - An in vitro study of diamorphine permeation through premature human neonatal skin. AB - The permeation kinetics of diamorphine through human premature neonatal cadaver skin over a range of gestational ages between 24 and 36 weeks was investigated using small diffusion cells. A strong inverse correlation was noted between the apparent permeability coefficient and the gestational age of the skin (P < 0.01; n = 26). The calculated apparent permeability coefficients decreased with gestational age from 6.0 x 10(-2) cm.hr-1 at 24 weeks' gestation to 5.2 x 10(-6) cm.hr-1 at 36 weeks' gestation. The amount of diamorphine remaining bound within the skin at the end of the in vitro experiments did not change significantly with gestational age of the skin. Diamorphine was subject to degradation over the course of the in vitro experiments to produce significant amounts of 6 monoacetylmorphine and evidence is presented to suggest that this was due to residual skin esterase activity. It is calculated that the steady-state flux rate of diamorphine through neonatal skin observed in these experiments would be sufficient to obtain a therapeutic plasma concentration of morphine assuming a 2 cm2 area for application and a delivery rate of 15 micrograms hr-1 kg-1. However, the prolonged half-life of morphine in the premature neonate would result in a delay of some hours before the attainment of this level. PMID- 8483843 TI - In vivo/in vitro correlation of experimental sustained-release theophylline formulations. AB - A novel multiparticulate sustained-release theophylline formulation, which consisted of spherical drug pellets coated with a rate-controlling membrane, was evaluated in vivo. Two preparations that differ solely in the coat thickness, and hence rate of in vitro drug release, were studied in comparison with a solution of the drug. Both preparations produced serum concentration profiles that are reflective of a slow and sustained rate of absorption. The in vivo release versus time profiles calculated using a deconvolution procedure showed that the two preparations differed in the rate but not the extent of drug release. Satisfactory correlation was also obtained between the in vivo and the in vitro results. When the two preparations were further compared using the parameters, time to reach peak concentration (Tp), peak concentration (Cp), and total area under the serum concentration versus time curves (AUC), a statistically significant difference was observed in the Tp and Cp values but not the AUC values, suggesting that the preparations differed in the rate but not the extent of absorption. In addition, the extent of absorption from both preparations was comparable to that obtained with the drug solution. PMID- 8483844 TI - Comparison of the pharmacokinetics and pharmacodynamics of the aldose reductase inhibitors, AL03152 (RS), AL03802 (R), and AL03803 (S). AB - The pharmacokinetics of AL03152 (RS) and its enantiomers, AL03802 (R) and AL03803 (S), were studied in the Sprague-Dawley rat following intravenous bolus administration. The enantiomers had differing pharmacokinetic profiles, while the racemic compound exhibited pharmacokinetic parameters approximating the mean values of the individual enantiomers. The total clearance (CLT) values of the two enantiomers were similar, but the intrinsic clearance (Cl(int)) was much greater for the S-enantiomer than for the R-enantiomer. The volume of distribution (Vss) for AL03802 (R) was threefold greater than that for AL03803 (S). The stereoselectivity in Vss could not be totally accounted for by the slight difference in serum protein binding of the isomers and resulted in a difference in the half-lives of the enantiomers. Only the R-isomer exhibited a persistent terminal elimination phase, consistent with more extensive tissue binding than the S-isomer. AL03152 enantiomers were equivalent in potency assessed from in vitro IC50 values toward rat lens aldose reductase and rat kidney L-hexonate dehydrogenase and lens EC50 values in diabetic rats. PMID- 8483845 TI - Pharmacokinetic monitoring in subcutaneous tissue using in vivo capillary ultrafiltration probes. AB - Capillary ultrafiltration probes were utilized for in vivo sampling of therapeutic drugs in awake rats. Capillary ultrafiltration probes implanted into subcutaneous tissue were able to follow the disposition of acetaminophen and theophylline. Ultrafiltration probes provided samples at a rate of 2-3 microL/min. Ultrafiltrates were analyzed by liquid chromatography with either UV or electrochemical detection. Simultaneous ultrafiltration and microdialysis probes and multiple ultrafiltration probes were used in individual animals to validate the technique. The pharmacokinetics of two well-established drugs, acetaminophen and theophylline, were monitored in awake, freely moving rats to demonstrate the viability of the technique. The half-life for acetaminophen was determined to be 20.9 +/- 1.0 min (n = 6) for a 2 mg/kg dosing. The half-life of elimination for theophylline was determined to be 3.0 +/- 0.1 hr (n = 4) for a 4 mg/kg dose. The capillary ultrafiltration probes exhibited a constant flow rate of 2.4 +/- 0.1 microL/min and removed 50 nL/min/mm of fluid from the extracellular space. Capillary ultrafiltration sampling is shown to be an excellent tool for in vivo monitoring of drug disposition and a suitable method for determining pharmacokinetic parameters in awake animals. PMID- 8483846 TI - Clinical pharmacokinetics and relative bioavailability of oral procaterol. AB - The pharmacokinetics and relative oral bioavailability of procaterol, an orally active beta 2-adrenergic agonist bronchodilator were evaluated in healthy volunteers. Procaterol was rapidly absorbed after oral administration. Mean plasma procaterol concentration-time profiles and pharmacokinetic parameters for both formulations were essentially superimposable. Following tablet administration, the mean Cmax was 358 pg/mL and the corresponding mean tmax was 1.6 hr. Mean renal clearance was 163 mL/min and accounted for approximately one sixth of the mean apparent oral plasma clearance (988 mL/min). The mean apparent elimination half-life of procaterol was 4.2 hr. Hepatic metabolism appears to be the primary mechanism for elimination of procaterol from the body, and first-pass metabolism may limit systemic bioavailability. PMID- 8483847 TI - Distinction between the depletion of opsonins and the saturation of uptake in the dose-dependent hepatic uptake of liposomes. AB - Opsonins play a role in the hepatic uptake of particles such as bacteria, lipid emulsion, and liposomes. The objective of this study was to distinguish between opsonin depletion and uptake saturation in the dose-dependent hepatic uptake of liposomes. The uptake of opsonized and unopsonized liposomes was determined in the isolated perfused liver. Serum (2.9 mL) was required to opsonize 1 mumol liposomes fully, indicating that a rat (250 g with 10 mL of serum) can opsonize 3.5 mumol liposomes. Next the dose effect on hepatic uptake of opsonized and unopsonized liposomes was examined. Saturation of uptake was found only for the opsonized liposomes. On the other hand, the hepatic uptake clearance decreased dose dependently from 4.31 to 0.79 (mL/min), with increasing doses from 0.075 to 17 mumol/250 g, respectively, after i.v. administration. Thus, the decrease in the hepatic uptake clearance at the medium dose was due to the saturation of uptake alone, and at the high dose it was due to opsonin depletion as well. These results show that the saturation of liposomal uptake in the liver and the depletion of opsonins occurred at different liposome dosage levels. PMID- 8483848 TI - Formycin B elimination from the cerebrospinal fluid of the rat. AB - The goal of this study was to determine whether specific transport systems are involved in nucleoside elimination from the cerebrospinal fluid (CSF). First, in vitro studies were carried out in isolated choroid plexus tissue slices from rat to ascertain the mechanisms of transport of formycin B, a model nucleoside analogue. 3H-Formycin B accumulated against a concentration gradient in the presence of an Na+ gradient in the isolated ATP-depleted choroid plexus tissue slices. This accumulation was reduced by high concentrations of unlabeled formycin B. Nitrobenzylthioinosine (NBMPR), an equilibrative nucleoside transport inhibitor, inhibited the uptake of formycin B in the absence of an Na+ gradient. These data suggest that both equilibrative and secondary active Na(+)-nucleoside transport systems are present in rat choroid plexus. In vivo, formycin B, together with inulin as a bulk flow marker, was injected into the lateral ventricle of the anesthetized rat with the aid of a stereotaxic device, and CSF was sampled from the cisterna magna at various times after injection. Twelve rats were randomized and divided into a low- and a high-dose group. The CSF clearance (CLCSF) of formycin B was significantly higher than the CLCSF of inulin in both animal groups (P < 0.01), indicating that formycin B is cleared from CSF by a pathway(s) in addition to bulk flow. Formycin B CLCSF was significantly lower in the high-dose group than in the low-dose group (P < 0.05), suggesting a saturable CSF elimination. The CLCSF of formycin B was also significantly reduced in animals treated with NBMPR (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483849 TI - The determination of diffusion coefficients in semisolids by Fourier transform infrared (FT-IR) spectroscopy. AB - A Fourier transform infrared (FT-IR) spectrometer with a horizontal attenuated total reflectance (ATR) cell was used to determine the diffusion coefficients of several liquids in two semisolid materials. The experimental setup was that of a system with one open and one closed boundary wherein the open boundary was maintained at constant concentration. While the liquid of interest was diffusing through the film of ointment, the concentration of liquid at the film surface in contact with the ATR crystal was determined at various times by means of IR absorption measurements. The depth of penetration of the IR radiation into the sample was approximately 0.6-0.9 microns at the wavelengths of analysis. Since the ointment thickness was 157 microns, it was reasonable to assume that only the penetrant reaching the lower boundary was being measured. The values of the diffusion coefficients were then calculated using an equation that appropriately modeled the aforementioned conditions. The liquids tested exhibited diffusion coefficients in anhydrous lanolin and in polyethylene glycol ointment that ranged from 0.56 to 7.2 x 10(-7) and 0.68 to 5.7 x 10(-7) cm2/sec, respectively. The expected molecular weight dependency was observed. PMID- 8483850 TI - Optimization of conditions for preparing 2- to 5-micron-range gelatin microparticles by using chilled dehydration agents. PMID- 8483851 TI - Molecular cloning of the alcohol/hydroxysteroid form (mSTa1) of sulfotransferase from mouse liver. PMID- 8483852 TI - Micellar solubilization of clofazimine analogues in aqueous solutions of ionic and nonionic surfactants. PMID- 8483853 TI - The influence of molecular volume and hydrogen-bonding on peptide transport across epithelial membranes. PMID- 8483854 TI - Cost of health care. PMID- 8483855 TI - Effective control of hypercholesterolemia in children with dietary interventions based in pediatric practice. AB - BACKGROUND: Based on recent recommendations, the number of hypercholesterolemic children who would require dietary therapy could overwhelm current preventive pediatric cardiology resources. No previous studies have established the efficacy of such therapy in the pediatrician's office. The purpose of this study was to evaluate two programs of office-based therapy. METHODS: We randomly assigned 295 children with hypercholesterolemia (> 185 mg/dl) two interventions: one single or four multiple 90-min sessions of family-oriented nutritional education, based in pediatric practices. We examined total cholesterol, 3-day food records, height and weight, and in the multisession group high-density lipoprotein cholesterol and triglycerides at the beginning and at intervals of 8.5-9 and 21 to 33 weeks (single-session and multisession groups, respectively). RESULTS: Total cholesterol was lowered equally in both treatment groups over the course of the study. This was accompanied by dietary changes: a decrease in calories derived from total and saturated fats, and increased intake of fiber, protein, and carbohydrate. However, more single-session patients withdrew from the program during the study. CONCLUSIONS: The two interventions were equally effective in lowering total and low-density lipoprotein cholesterol and in reducing intake of total and saturated fat. However, the higher completion rate of the multisession group suggests that this approach may be the more effective. PMID- 8483856 TI - Do obese children become obese adults? A review of the literature. AB - BACKGROUND: Obese children may be at increased risk of becoming obese adults. To examine the relationship between obesity in childhood and obesity in adulthood, we reviewed the epidemiologic literature published between 1970 and July 1992. Comparison between studies was complicated by differences in study design, definitions of obesity, and analytic methods used. Although the correlations between anthropometric measures of obesity in childhood and those in adulthood varied considerably among studies, the associations were consistently positive. RESULTS: About a third (26 to 41%) of obese preschool children were obese as adults, and about half (42 to 63%) of obese school-age children were obese as adults. For all studies and across all ages, the risk of adult obesity was at least twice as high for obese children as for nonobese children. The risk of adult obesity was greater for children who were at higher levels of obesity and for children who were obese at older ages. CONCLUSION: The wide range of estimates in this literature are, in part, due to differences in study designs, definitions of obesity, ages at which participants were measured, intervals between measurements, and population and cultural differences. PMID- 8483857 TI - Consistent lack of association between breast cancer and oral contraceptives using either hospital or neighborhood controls. AB - BACKGROUND: Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls. METHODS: To determine whether this association differs according to type of controls, interview data from 131 incident cases of breast cancer were compared with those of 189 hospital controls and 182 neighborhood controls Study subjects were white females recruited between 1973 and 1975 from among residents of Baltimore City and County ages 18 to 59 years. RESULTS: Adjusted relative odds of breast cancer related to ever versus never use of oral contraceptives were 1.0 and 0.8, using hospital and neighborhood controls, respectively. Relative odds did not increase proportionally to duration of oral contraceptive use or to progestogen potency. Although few subjects had used oral contraceptives for more than 2 years, almost all pill brands contained more than 49 micrograms of ethinyl estradiol or of mestranol. CONCLUSIONS: Results from the present study do not support the hypothesis that early preparations of oral contraceptives increased breast cancer risk among white women, regardless of whether controls are neighbors of the cases or hospital patients. However, its conclusions cannot be generalized to women who began taking the pill before their first full-term birth or took it for more than 2 years. PMID- 8483858 TI - An ecological study of the relationship between dietary fat intake and breast cancer mortality. AB - METHODS: An ecologic study of the relationship between the per person supply of animal fat, vegetable fat, and fish fat obtained from the Food and Agricultural Organizations of the United Nations food balance sheets and female breast cancer mortality rates from 1961 to 1986 was carried out using data from 30 countries. RESULTS: In univariate analysis, a lag period of about 10 years was found for the highest correlations between breast cancer mortality rates and animal fat minus fish fat intake in the age groups 50 years and above. Age classes 50 years and above showed higher correlations between fat intake and breast cancer mortality than those below 50 years over the periods examined. In multiple regression analysis, animal fat minus fish fat intake showed a highly significant positive relationship with the breast cancer mortality rates (P < 0.001) in age groups 50 years and above for all the periods examined. Whenever significant, dietary fish fat intake correlated negatively (P < 0.001) and vegetable fat positively (P < 0.01) with breast cancer mortality. Moreover, a significant positive relationship (P < 0.001) between the change over time in animal fat minus fish fat intake and that in breast cancer mortality was found. To confirm these findings we also examined the correlation between breast cancer mortality and fat consumption data obtained from 46 dietary surveys performed in 17 countries. CONCLUSIONS: Although slightly less significant, the findings corroborate the relationships obtained by using FAO data. Our findings confirm the highly significant positive association between dietary fat and breast cancer mortality. The effect differs according to the type of fat consumed. PMID- 8483859 TI - Age, sex, educational attainment, and race/ethnicity in relation to consumption of specific foods contributing to the atherogenic potential of diet. AB - BACKGROUND: We examined which specific foods contributed to the atherogenic potential of diet in population segments defined by age, sex, educational attainment, and race/ethnicity. Data from the 1989 New York State Healthy Heart Program baseline survey were analyzed. METHODS: This telephone survey was conducted in eight communities (total population approximately 1.24 million people) in New York State. Response rate was 65.5% (N = 4,179); 3,606 subjects ages 20 to 64 years who reported their level of educational attainment with self described ethnicity of white (N = 1,935), black (N = 1,035), or Hispanic (N = 636) were retained in the analysis. Diet was assessed using a 17-item food frequency questionnaire which focused on commonly eaten food high in saturated fat and cholesterol. Connor's cholesterol/saturated-fat index was used as a scale of the atherogenic potential of the diet. RESULTS: Eggs, whole milk, cheese, beef, and butter/margarine were the foods contributing most to the cholesterol/saturated-fat index score in all age-, sex-, and race/ethnicity specific population segments examined, together contributing a total of 52 to 72% of the cholesterol/saturated-fat index score as measured by the 17-item diet questionnaire. CONCLUSIONS: The implication for public health campaigns directed at reducing the atherogenic potential of diet atherogenicity and for primary care practitioners seeking to influence the diet of patients with high blood cholesterol is that substitutions of less atherogenic food choices for these five foods would appear to be appropriate for most adults. PMID- 8483860 TI - Coffee consumption and serum cholesterol. GISSI-EFRIM Study Group. AB - The relationship between coffee consumption and serum cholesterol was examined in the comparison group of a case-control study of myocardial infarction involving 642 patients from various Italian regions who were hospitalized for diseases having no relationship to cardiovascular disease risk factors. Overall mean total cholesterol was 198.9 mg/dl. Mean cholesterol values (in mg/dl) standardized for age, sex, and smoking habits were 204.0 for nonconsumers of coffee, 194.8 for drinkers of one cup per day, 196.5 for two, 202.9 for three, 205.9 for four, and 206.5 for five or more cups per day. Thus, serum cholesterol levels were higher in non-coffee drinkers than in moderate drinkers; among coffee drinkers, however, there was a direct, although moderate, relationship between the amount of coffee consumed and the total cholesterol levels. A similar though less consistent pattern was also evident across separate strata of sex, age, and smoking habits, and the association was appreciably greater among younger subjects (below age 50). Although mean cholesterol levels in this Italian dataset were lower than those in other populations from northern Europe and the United States, the relative difference between moderate and heavy drinkers was proportionally similar to that reported in other studies. These results are of special interest since most Italian coffee (i.e., mocha or espresso) is unfiltered. PMID- 8483861 TI - The role of childbirth in smoking cessation. AB - BACKGROUND: Many women abstain from smoking during pregnancy, but relapse rates in the first year postpartum are high. The impact of childbirth on long-term abstinence from smoking is unknown for both women and men. METHODS: We assessed the impact of childbirth on long-term abstinence from smoking (minimum: 17 months, much longer in most cases) in a retrospective cohort analysis of 925 women and 1,494 men who were interviewed in 1984 to 1986 in the national baseline survey of the German Cardiovascular Prevention Study. RESULTS: Among women, smoking cessation rates resulting in long-term abstinence were about three times higher during the year of childbirth and the year before than in other years (adjusted rate ratio, 2.98; 95% confidence interval, 2.21-4.03). Childbirth was also associated with increased cessation rates among better educated men (adjusted rate ratio for this subgroup, 1.84; 95% confidence interval, 1.16 2.92), but not among less educated men. Nevertheless, childbirth led to long-term abstinence from smoking only in a small minority of smoking mothers and fathers. CONCLUSION: Despite increased cessation rates around childbirth, more effective measures are needed to promote sustained abstinence after childbirth among both parents. PMID- 8483862 TI - Diffusion of a school-based substance abuse prevention program: predictors of program implementation. AB - BACKGROUND: The present study addresses diffusion of a psychosocial-based substance abuse prevention program, including: (a) teacher adoption, implementation, and maintenance; (b) teacher characteristics associated with implementation; (c) the relationship between integrity of program delivery and program outcomes; and (d) the effectiveness of teacher training and school principal involvement in increasing implementation. METHODS: Participants were teachers (n = 60), school principals (n = 25), and fifth-grade students (n = 1147) from four Los Angeles area school districts. Districts were randomly assigned to an intensive or brief teacher training condition. Schools were randomly assigned to a principal-intervention or a no-principal-intervention condition. Assessments included teacher and principal self-reports, classroom observations of program delivery, and evaluation of immediate program outcomes. RESULTS: During the first year, 78% of trained teachers implemented one or more program lessons. During the second year, only 25% maintained implementation of the program. Implementors reported fewer years of teaching experience and stronger self-efficacy, enthusiasm, preparedness, teaching methods compatibility, and principal encouragement than did nonimplementors. The principal intervention increased rates of implementation, but the intensive teacher training did not. Integrity of program delivery was positively associated with immediate program outcomes. CONCLUSIONS: Program implementation was highly variable, suggesting that widespread teacher use of psychosocial-based programs cannot be taken for granted. Strategies for increasing implementation and maintenance need to be developed. PMID- 8483863 TI - Predictors and reasons for relapse in smoking cessation with nicotine and placebo patches. AB - BACKGROUND: The reasons for relapse to smoking are not fully understood but several factors are of importance. Addiction to nicotine seems to play a prominent role but there are several other contributing factors. METHODS: To determine predictors of outcome in smoking cessation, we performed univariate and multivariate analyses in a large smoking cessation trial comprising 289 subjects. Weight gain and withdrawal symptoms were analyzed separately as predictors. To determine self-perceived reasons for relapse we created a questionnaire, which was answered by 132 relapsers. RESULTS: Previous attempts to quit smoking and a low saliva cotinine concentration were significantly associated with abstinence in the nicotine-treated group. A trend toward higher abstinence rates was found among males and among subjects with a low nicotine dependency score. Logistic regression analysis showed higher success rates in subjects with the largest weight gain during the first weeks of quitting in contrast to higher relapse rates in subjects who had the greatest weight gain after 3 months. A high score on withdrawal symptoms was not predictive of relapse. Subjects with "slips" had a markedly increased relapse rate. Craving for cigarettes was the most often self reported (48%) reason for relapse. CONCLUSIONS: The relation between weight gain, withdrawal scoring, and outcome seems rather complex. Craving for cigarettes was the most reported reason for relapse. PMID- 8483864 TI - Cigarette smoking recidivism after participation in the "Five-Day Plan to Stop Smoking" in northeastern Italy. AB - BACKGROUND: This study was designed to evaluate the efficacy of the "Five-Day Plan to Stop Smoking" (the "Five-Day Plan") in helping smokers to give up the habit and to identify the characteristics of those smokers who succeeded in quitting. METHODS: Five hundred and forty-five smokers (363 men, mean age 41 years, and 182 women, mean age 37 years) of a total of 683 (80%) who participated in eight courses of the Five-Day Plan, held in northeastern Italy between October 1985 and April 1988, constitute the study group. They were contacted from 28 to 70 months after their participation in the Five-Day Plan. RESULTS: Approximately 70% of smokers tried to stop smoking for fear of smoking-related health hazards, and 15% (18% of men and 9% of women, P < 0.001) of these stopped because of smoking-related diseases or symptoms. Overall, 18% of the participants interviewed relapsed to cigarette smoking within 1 month after having taken the course, 44% within 1 year, and 59% after 5 years. Higher rates of recidivism after the Five-Day Plan were recorded among women than among men (55 and 39% after 1 year, respectively). Among men, older age and heavy smoking were significantly associated with a reduced probability of relapsing. Among women, a high level of education was the only significant predictor of smoking recidivism. CONCLUSIONS: These data indicate that the Five-Day Plan is useful in helping smokers who are already predisposed to quit their habit, but its efficacy seems to be largely restricted to men, in particular to older and heavier smokers. PMID- 8483865 TI - Interest in genetic testing for colon cancer susceptibility: cognitive and emotional correlates. AB - BACKGROUND: Recent advances in human genetics have led to the identification of markers for cancer susceptibility. Nevertheless, little is known about the public's interest in clinical genetic testing for cancer-related markers. METHODS: A random-digit-dial telephone survey of 401 adult residents of Utah was conducted during the summer of 1990. Respondents were randomized to one of three question frames and asked about their interest in a potential genetic test for colon cancer susceptibility. They were also asked to rate their risk for colon cancer, how often they worried about contracting any type of cancer, and how often they felt worried and nervous during the past year (trait anxiety). RESULTS: Eighty-three percent of respondents expressed interest in genetic testing. Level of interest was most strongly correlated with perceived risk for colon cancer (r = 0.21, P < 0.001). Responses were not affected by the use of different question frames. CONCLUSIONS: These results show a high level of public interest in genetic testing for colon cancer susceptibility. The data also suggest that anxiety does not undermine interest, but future research must determine whether this relationship is limited to hypothetical judgments such as those studied here. PMID- 8483866 TI - [Local and systemic side effects of inhaled corticosteroids--what is reliable?]. PMID- 8483867 TI - [Thoracoscopic lung biopsy in diagnosis of interstitial lung diseases]. AB - Thoracoscopic lung biopsy is accepted to be an appropriate method in diagnosing interstitial lung diseases when lung tissue examination is needed for accurate diagnosis. In our study of 30 patients with chronic interstitial lung diseases a high sensitivity of 97% was reached similar to the yield reported from open lung biopsy techniques. The manyfold described handicap of long lasting pleural fistula after thoracoscopic biopsies could be prevented in most cases by sealing the biopsy site with a fibrin layer. Thus the mean pleural drainage-time was reduced to 3.7 +/- 1.0 days and only 3 out of the 30 patients required a prolonged drainage up to 11 days. There were only a few minor complications except in one patient who developed an etiologically unclear pulmonary edema shortly after the procedure. However the results obtained by this modified bioptic technique are encouraging and confirm again the efficacy and safety of thoracoscopic lung biopsy in diagnosing interstitial lung diseases. PMID- 8483868 TI - [Autochthonous European dirofilariasis of the lung]. AB - Two intrapulmonary round nodules were identified by x-ray examination in a 45 year old German woman during an examination conducted before her employment who had been complaining of pain in the right side of the thorax and of mild coughing irritation and tiredness for several months prior to the health check. Since the intraoperative frozen section did not show any malignancy, and atypical resection of the two involved segments was performed. Histological processing of the surgical specimens showed two spherical ischemic necroses surrounded by a connective tissue border with inflammatory infiltration. In the centre of the larger of the two necrotic lesions a parasite was seen intravascularly, which because of morphological and serological findings, was identified as a Dirofilaria. It must be assumed that the infection of this patient occurred during a stay in Corsica where these nematodes are endemic in several mammal hosts. The patient was therefore suffering from an autochthonous European dirofilariasis of the lung. Only two cases of this infection acquired in Europe have been reported so far. PMID- 8483869 TI - Characterization of new monoclonal antibodies directed against normal human exocrine pancreas and pancreatic adenocarcinomas. AB - A series of 12 cell fusions of BALB/c mice spleen cells with the SP2/O-Ag14 mouse myeloma cell line were performed after immunizations with normal human pancreas to generate monoclonal antibodies (mAbs) with high affinity against antigens of the exocrine pancreas. The immunohistologic tissue screening resulted in the selection of 14 clones that were further characterized on frozen tissues, tumor cell lines, and lectin binding assays. Four mAbs reacting with pancreatic acini detected granular antigens and three mAbs reacted with acinar cell membrane antigens. Six other clones reacted with pancreatic ducts; among these were three clones positive with antigens in both acini and ducts. Among the clones reactive with secretory products, there was one pair of mAbs identified as pancreas specific (P78C9/P79D4); the other secretory antigens (identified by P97F3 and P109H1) were also detectable in other exocrine organs, but were absent from the gastrointestinal mucosa. Two clones reactive with acinar cell membranes (P96H2 and P100H1) were also positive with hepatocytes. All but four antigens were detectable in pancreatic cancer cell lines Capan-1, Capan-2, and DAN-G. On the whole, immunizations were more effective using whole pancreatic tissues (eight clones selected) compared with single-cell suspensions as immunogen (four clones) or cell membrane preparations (two clones). Therefore, the immunization and screening strategies used in this study resulted in the generation of new mAbs against specific substructures of the exocrine pancreas. The shared expression of some of these antigens with other exocrine organs and pancreatic adenocarcinoma cell lines suggests that these mAbs detect antigens that are characteristic for the exocrine system and could therefore be useful for the study of the exocrine pancreas and pancreatic adenocarcinomas. PMID- 8483870 TI - Radioimmunoimaging of xenograft pancreatic cancer with 131I-monoclonal antibody P2. AB - Monoclonal antibodies (McAbs) to pancreatic cancer were developed by fusing SP2/0 cells and splenocytes from Balb/c mice immunized with CH-2 cells. The specific binding rates of McAb P1 and P2 were 40.1 and 43.8%, respectively, shown by binding radioreactivity assay in vitro, which were in sharp contrast with those of control groups (p < 0.05). The biodistribution of radioiodinated McAb P2 was studied by measuring parameters of tumor-specific radioreactivity in nude mice bearing CH-2 tumors. The ratios of tumors to nontumors were all > 2 at 48 h. The localization index of cancer and the ratio of tumor to pancreas were 4.05 and 4.16, respectively, at 72 h. Therefore, 131I-McAbs may be useful for radioimmunoimaging (RII) of pancreatic cancer. After intraperitoneal injection of 131I-McAb P2 into tumor-bearing nude mice, imaging of xenograft pancreatic cancer became increasingly distinct with the nonspecific background fading, especially in the period of 72-96 h. Examination of pancreatic cancer tissues by immunohistochemical methods revealed that McAb P2 was strongly positive (86%) in comparison with other tumors and normal tissues. The results demonstrated that clinical RII of pancreatic cancer was feasible with McAb P2. PMID- 8483871 TI - Resistance of the human fetal beta-cell to the toxic effect of multiple low-dose streptozotocin. AB - The human fetal beta-cell is different from the adult beta-cell not only in that it is unable to release significant amounts of insulin during an acute glucose challenge, but also in that it is resistant to the toxic effects of a bolus of streptozotocin (STZ) and chronic exposure to cytokines tumour necrosis factor alpha and interferon-gamma. To examine further the differences between the immature and mature beta-cell, these cells were exposed to multiple low doses of STZ (MLS) both in vivo and in vitro, the regimen used being classically toxic to rodent adult beta-cells. The in vivo experiments were conducted after the tissue had been grafted into the athymic mouse. There was no adverse effect of MLS on the insulin content of engrafted human fetal pancreatic explants, either 1, 4, or 15 weeks after the injection of 70 mg/kg/i.p. STZ daily for 5 days. Diabetes, induced in the mice by MLS or a bolus of STZ, was reversed in five of seven MLS treated mice at 59 +/- 8 days and four of seven STZ-treated animals at 75 +/- 10 days (no significant difference). The growth rate of the implanted tissues also was not adversely affected by the MLS, nor was the percentage of beta-cells 2 weeks after completion of the MLS. In contrast, mouse fetal beta-cells transplanted into the athymic mouse were adversely affected, their insulin content 2 weeks after MLS being only 0.7% that of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483872 TI - Marked islet amyloid polypeptide-positive amyloid deposition: a possible cause of severely insulin-deficient diabetes mellitus with atrophied exocrine pancreas. AB - An insulin-deficient 51-year-old man was put on dietary therapy and sulfonylurea (SU). Although there was good glycemic control for 2 years, the fasting blood glucose (FBG) level increased gradually over the subsequent 4-year period, and there was a marked increase in body weight. Secondary failure of SU therapy 20 years after the initial diagnosis led to insulin therapy. The FBG became unstable, and the C-peptide response disappeared. The patient died of nonketotic hyperosmolar coma and pneumonia at the age of 87. At autopsy, the pancreas showed marked atrophy (32 g) with extensive fatty degeneration. Islets replaced by islet amyloid polypeptide (IAPP)-positive amyloid (IAPP-AM) amounted to 77% in the tail, 74% in the body, and 73% in the head of the pancreas. All islets were positive for IAPP-AM throughout the pancreas, except for a pancreatic polypeptide rich lobe, where none were positive. IAPP-AM-positive islets had also undergone fatty change of the surrounding pancreatic acinar cells. beta-Cells decreased remarkably in number and were displaced to the periphery of the islets by the IAPP-AM deposits. These findings suggest that IAPP-related diabetes could have a progressive course, with secondary oral hypoglycemic agent failure and the subsequent development of severe insulin deficiency similar to that seen in insulin-dependent diabetes mellitus. PMID- 8483873 TI - Synthesis-secretion coupling of insulin: effect of pregnancy and lactation. AB - Synthesis-secretion coupling of insulin was determined using perfused pancreata taken from either control, pregnant, or lactating female Sprague-Dawley rats. The pancreata were stimulated for 3 h with one of the two glucose concentrations used: either 150 or 300 mg/dl. In the case of pregnancy, the pancreata exhibited a twofold hypersecretory activity in response to the physiological glucose level of 150 mg/dl. Net insulinogenesis did not occur in response to the normoglycemic glucose concentration, and, as with the controls, there was an overall depletion of insulin stores. There was no insulin hypersecretion at the hyperglycemic level of 300 mg/dl, but net insulinogenesis did occur; however, it matched that of the controls. Therefore, the hypersecretion of insulin ascribed to pregnancy appears to be a function of the secretory process only, to be most demonstrable under normoglycemic conditions, and not to be due to enhanced synthesis-secretion coupling. In the case of pancreata from lactating rats, just the converse was observed. Compared with controls, there was no substantial difference in insulin secretion by pancreata from lactating rats at either glucose level or of insulinogenesis under normoglycemia conditions. However, when glucose was at a hyperglycemic load in the lactating group, not only was there no net insulinogenesis, but this condition actually resulted in a depletion of intracellular insulin stores (as opposed to both the control and the pregnant groups). This suggests that the hypoinsulinemia noted during lactation may be related to a reduced capacity of those beta-cells to synthesize insulin the face of prolonged hyperglycemic stimulation. PMID- 8483874 TI - Nesidioblastosis as a mechanism to prevent fibrosis-induced diabetes after pancreatic duct obstruction. AB - Does obstruction of the main pancreatic duct that results in exocrine atrophy also result in diabetes? We followed 11 mongrel dogs for 3 years after approximately three-fourths of the pancreas had been removed and the main pancreatic duct obstructed in the pancreatic tail remnant. At 3 years after surgery, all dogs showed total exocrine atrophy (remnants weighed 0.2-1.2 g). None of the animals became diabetic despite only 6% of the original pancreatic tail remaining. During the 3-year period, fasting blood insulin increased during the last half of the study, and this was associated with islets that were 1,300% larger than in control animals (nesidioblastosis). An in situ pancreatic remnant with an obstructed duct and total exocrine atrophy can maintain a nondiabetic state for > 3 years. Perhaps the mechanism is associated with the observed nesidioblastosis. PMID- 8483875 TI - Effects of pancreaticobiliary diversion and gastric fundectomy on azaserine induced pancreatic carcinogenesis in the rat. AB - The effects of pancreaticobiliary diversion (PBD) and gastric fundectomy on the pancreas in azaserine-treated rats were studied over 14 months. Sham-operated azaserine-treated animals served as controls. A significant increase in pancreatic weight and total DNA and protein content was found in PBD-operated and fundectomized animals. DNA flow cytometry showed a significantly increased ratio of tetraploid to diploid cells in pancreatic tissue in both experimental groups. Mean values of all these variables were significantly higher after PBD than after fundectomy. Acidophilic atypical acinar cell foci of the pancreas were observed in all of the experimental and 75% of the control animals. The volume density of these foci was significantly higher in each experimental group than in the controls. The volume density, radioactive thymidine labeling index, and mitotic index of the foci were significantly higher after PBD than after fundectomy. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. It is concluded that not only PBD with endogenous hypercholecystokininemia, but also fundectomy with endogenous hypergastrinemia lasting about half of the life span in rats, induces pancreatic hypertrophy and enhances the development of precancerous pancreatic changes after azaserine treatment. In comparison with PBD, fundectomy caused less pronounced changes and no observable neoplasia. PMID- 8483876 TI - Severe subcellular damage in the rat exocrine pancreas after pancreatobiliary diversion. AB - Cholecystokinin (CCK) may contribute to the genesis of both pancreatic carcinoma and acute pancreatitis. By transposing a long segment of jejunum to lie between the pylorus and the duodenal papilla, pancreatobiliary diversion (PBD) causes a persistent increase in circulating CCK levels, as the normal feedback inhibition of jejunal CCK release by pancreatic juice is evaded. A number of morphological, physiological, and acinar cytokinetic changes ensue. This investigation has examined the ultrastructural changes in pancreatic acinar cells after PBD in the presence and absence of CR1409 (lorglumide), a CCK receptor antagonist. After 14 days there was degranulation and vacuolation of acinar cells with involvement of the enzyme acid phosphatase. The presence of morphologically distinct extracisternal acid phosphatase indisputably predisposed acinar cells to severe damage. Treatment with CR1409 largely prevented degranulation after PBD, but vacuolation of acinar cells still occurred, indicating a possible toxic effect of the receptor antagonist. This is the first report of CCK itself, rather than one of its analogues, causing in vivo pancreatic damage that is generally considered as a forerunner to acute pancreatitis. This is of fundamental importance to the understanding of the earliest stages of the disease. PMID- 8483877 TI - Acute pancreatitis is not a cause of chronic pancreatitis in the absence of residual duct strictures. AB - It has been shown that intraductal injections of bile salts into the bile pancreatic ducts of dogs or rats were immediately followed by acute hemorrhagic pancreatitis and, some months later, by persisting chronic pancreatitis. The study described in this article was designed to test the assumption that these chronic lesions were due to ductal strictures secondary to the toxic effect of bile salts. The bile-pancreatic ducts of 100 rats were injected with 0.2 ml of a solution containing 4 microM Na taurodeoxycholate and 0.2 microM trypsin. The 66 survivors were killed at intervals from 1 day to 2 months following the induction of acute pancreatitis. Four to six sections were done in the first series, and serial 15-micron sections of the entire pancreas were taken from rats surviving 2 months. These showed that from the sixth day on, the largest ducts draining pathological areas were obstructed by fibrosis. Distal to this obstruction, intralobular ducts were dilated and their epithelia flattened or atrophied. Acini were atrophied and replaced by peri- and intralobular fibrosis. Lesions were limited to areas drained by obstructed ducts, with the rest of the parenchyma being normal. We conclude that in experimental animals, as in human beings, chronic lesions that persist after acute pancreatitis are due to duct obstruction, not to acinar necrosis. PMID- 8483878 TI - Pancreatic necrosis: an early finding in severe acute pancreatitis. AB - Despite the clinical importance of pancreatic necrosis in the course of acute pancreatitis, little is known about when it develops. Serum C-reactive protein (CRP) is a reliable parameter with a high deduction rate for pancreatic necrosis. We analyzed 199 patients with acute pancreatitis. The development of pancreatic necrosis was ascertained by a daily measurement of serum CRP in 45 patients with contrast-enhanced computed tomographic-proven necrotizing pancreatitis. In all 45 cases, the criteria for pancreatic necrosis were satisfied within the first 4 days of the onset of symptoms. This indicates that pancreatic necrosis is an early finding that develops within hours. PMID- 8483879 TI - Effect of L-364,718 (CCK receptor antagonist) on exocrine pancreatic secretion of adrenalectomized rats. AB - The exocrine pancreatic secretion of control and adrenalectomized rats treated with L-364,718 was studied. The blockade of the action of endogenous cholecystokinin (CCK) in the control animals was reflected in a reduction of basal pancreatic secretion. This effect was reversed by the administration of submaximal doses of CCK-8. Under treatment with L-364,718, no decrease in pancreatic weight was observed. From this it may be deduced that factors other than CCK act on the pancreas to maintain the processes of enzyme synthesis and storage. Adrenalectomy reduced the weight of the pancreata; the main cause of this was the depletion of zymogen granules, which has been reported in adrenalectomized rats and is accompanied by a reduction in enzyme secretion, especially that of amylase. By contrast, the administration of L-364,718 from the very first moments after adrenalectomy leads to a retention of pancreatic enzymes. This effect is reflected in the maintenance of pancreatic weight and a secretory capacity in response to submaximal doses of CCK-8 similar to that of nonadrenalectomized animals. Accordingly, in the absence of glucocorticoids, endogenous CCK dominates the secretory process because when the action of this secretagogue is prevented by the administration of L-364,718, the discharge of proteins able to be secreted in response to a suitable stimulus is inhibited. PMID- 8483880 TI - To immunostain or not to immunostain, that is the question. PMID- 8483882 TI - H-ras-1 point mutations in soft tissue sarcomas. AB - The H-ras-1 protooncogene is activated by single base substitutions occurring in either codon 12, 13, or 61. These mutations have been described with varying frequencies in several human tumor types. Since ras oncogenes were first discovered as the transforming sequences of Harvey and Kirsten murine sarcoma viruses (which also contain activating point mutations compared to the homologous cellular sequences), we wished to investigate the possibility that ras mutations might also occur in human sarcomas. We extracted DNA from six malignant fibrous histiocytomas (MFH), three embryonal rhabdomyosarcomas (ER), one alveolar rhabdomyosarcoma, one pleomorphic rhabdomyosarcoma, and one leiomyosarcoma. The DNA from regions flanking codons 12/13 and codon 61 was amplified by the polymerase chain reaction and sequenced with an automated DNA sequencer. As controls, we amplified and sequenced normal DNA (placenta) and DNA with known point mutations (T24 bladder carcinoma cells). We found three cases with mutations, all occurring in codon 12. One ER showed a G-to-T mutation in the second position of codon 12 (coding for valine instead of glycine). Two MFHs showed G-to-A mutations in the second position of codon 12 (coding for aspartic acid instead of glycine). Although a limited number of cases were sampled, we conclude that study of H-ras-1 mutations may be relevant to MFH and ER. Additional studies of N and K-ras mutations as well as more cases investigating H ras will be required before we can ascertain the significance of ras mutations in the oncogenesis of human soft tissue sarcomas. PMID- 8483881 TI - Focal and segmental glomerulosclerosis in nephrotic syndrome: a new profile of adult nephrotic syndrome in Zaire. AB - In order to assess renal pathology, 92 clinically well-documented cases of nephrotic syndrome (NS) in adults (median age: 29) were systematically biopsied upon admission to the University Hospital of Kinshasa, between 1986 and 1989. All biopsies were paraffin embedded and histologically assessed by the routine methods of light microscopic examination. Histologic lesions were classified according to standard criteria. Focal and segmental glomerulosclerosis (FSG) was found in 41% of patients. The remaining 59% included minimal epithelial disease or minimal change nephropathy (MCN) responsive to corticosteroid therapy (14%), proliferative glomerulonephritis (PGN) (11%), membranous glomerulopathy (MGP) (10%), amyloidosis (10%), membrano-proliferative glomerulonephritis (MPGN) (8%), and "end stage kidney" (ESK) (7%). These results strikingly indicate the high prevalence of FSG. In comparison with previous findings from the same milieu, there is a seven-fold increase of this entity (41% versus 6%). The findings herein reported define a new histologic profile of NS in Zaire, characterized by the predominance of FSG. While in the past the vast majority of NS (52%) were putatively related to the intercurrent parasitic diseases, among which malaria was the chief etiology, similar associations were less important. Instead, no definite causative agent emerged for this apparently idiopathic condition. Further epidemiological and morphological intercorrelation studies, as well as the studies aimed at the relationships with AIDS, are in progress, with the purpose of identifying putative etiologies and risk factors responsible for the increase of FSG in Zaire. PMID- 8483883 TI - Immunohistochemistry of childhood sarcomas: old and new markers. AB - The frequent difficulties encountered in the diagnosis of pediatric sarcomas, caused by the lack of observable differentiation at the light microscopic level, has led to the routine use of immunohistochemistry in pediatric surgical pathology. To a large degree the advent of this staining technique has led to the correct assessment of many perplexing lesions that previously would have been given inconclusive diagnoses. However, with increased usage and testing, it has become apparent that there are few, if any, "magic bullets" in immunohistochemistry for pediatric pathologists. Thus, it behooves diagnosticians to be careful in the usage of this technique, to be aware of possible discrepancies in its results, and to remember the ancillary nature of its application. The following article will review selected markers commonly used in pediatric surgical pathology, from both previous reports and the author's perspective, and will briefly consider several new phenotypic markers which have potential utility with childhood sarcomas. PMID- 8483884 TI - Immunohistologic characterization of gastrointestinal stromal tumors: a study of 82 cases compared with 11 cases of leiomyomas. AB - The histogenesis of stromal tumors of the gastrointestinal tract (GIST) is still controversial. Recent immunohistologic and ultrastructural studies have been inconsistent and suggest various cells of origin. In view of these uncertainties, we studied the immuno-profiles of 82 cases of GISTs and 11 cases of stromal tumors that we classified as leiomyomas based on histology. The 82 cases of GIST were subclassified as spindle or epithelioid type stromal tumors based on the predominant pattern and further divided into benign (< 5 cm in size and < 5 mitosis/50 HPF), malignant (> 5 mitosis/50 HPF), and borderline lesions (> 5 cm and < 5 mitosis/50 HPF). A panel of antibodies was used to characterize differentiation toward myogenic cells [pan-muscle actin (HHF-35), alpha-smooth muscle actin (SMA) and desmin], Schwann cells (S-100 protein), enteric glial [(glial fibrillary acidic protein (GFAP)], and nerve cells (neurofilaments). All leiomyomas were strongly positive for the three muscle markers. Of the 82 GISTs, only four cases (5%) were positive for desmin. However, 63% (52 cases) were positive with anti-pan-muscle actins and 39% (32 cases) were positive with anti SMA. Compared with gastric tumors, the positivity rates were much higher for small bowel tumors. Seventy-nine cases (96%) were positive for vimentin, only five cases and two cases were focally and weakly reactive for S-100 protein and GFAP respectively, and none stained for neurofilaments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483885 TI - Quantitative criteria for clonality in the diagnosis of B-cell non-Hodgkin's lymphoma by flow cytometry. AB - Fifty-three cases of B-cell non-Hodgkin's lymphoma (BNHL) and 41 cases of non BNHL lesions were retrospectively evaluated for the quantitative features of restricted surface light chain expression, pan B-cell antigens, pan T-cell antigens, and T-helper and T-suppressor phenotype using flow cytometry. Decision limit analyses were applied to multiple quantitative indices of immunophenotype to establish criteria for the detection of clonal proliferation associated with BNHL or non-BNHL conditions. Two data expressions (percent population and relative ratios) were simultaneously analyzed. The percent population measures were amenable to parametric analyses; the ratio data were amenable to nonparametric analyses only. Acceptable diagnostic specificity and sensitivity were obtained using decision limits of 75% kappa light chain and 65% lambda light chain for the detection of clonal proliferations associated with BNHL. Comparable diagnostic criteria for light chain ratios of 3:1 and 2:1 were similarly confirmed for cases of kappa clonal and lambda clonal proliferations, respectively. Neither the percent of B-cells present nor the ratio of T-helper cells to T-suppressor cells were of utility in the diagnosis of BNHL. These data confirm the numerical criteria for clonality previously obtained by cell counting studies of immunocytochemical preparations and characterize quantitative criteria for aid in the diagnosis of BNHL based on restricted surface light chain expression as measured by flow cytometry. PMID- 8483886 TI - Immunocytochemical identification of T-cells in HIV-1 encephalitis: implications for pathogenesis of CNS disease. AB - T-lymphocytes enter the brain in viral encephalitides. The monoclonal antibodies UCHL1 and Leu22 are widely used to identify these cells; however, both antibodies cross-react with peripheral blood monocytes, cells ontologically related to brain macrophages and microglia. This study examines the nature of UCHL1- and Leu22 positive cells in HIV-1 encephalitis, and investigates whether they carry the gp41 epitope of HIV-1. Formalin-fixed sections of brain from eight AIDS patients were double-stained using combinations of UCHL1 and Leu22 antibodies with the lectin Ricinus communis agglutinin (RCA), a lectin that binds to microglia, macrophages, and multinucleated giant cells (MNGC), or antibody to the gp41 transmembrane protein of HIV-1 and UCHL1. Some sections were also stained with the OPD4 antibody to helper/inducer T-cells. Small round cells were single stained for UCHL1 and Leu22 in all cases. A few cells having morphologic characteristics of microglia, macrophages, and MNGC were observed using double stains employing UCHL1 or Leu22 and RCA, or UCHL1 or Leu22 and anti-gp41. Small round cells positive for both UCHL1 or Leu22 and gp41 could represent either macrophages or lymphocytes. The presence of small round cells positive only for UCHL1 or Leu22 in double-stained sections strongly suggests that T-cells are present in the brain in HIV encephalitis. Only a few of these cells were positive with OPD4 antibody for T-helper cells. Inability to demonstrate unequivocally HIV 1-infected T-cells suggests that microglia and macrophages, not T-cells, are the more important reservoirs of retrovirus in the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483887 TI - Occurrence of melanin in pheochromocytoma. AB - Melanin or a melanin-like pigment was observed in six of 19 pheochromocytomas. The intracellular pigment was Fontana-positive, bleach-labile dark brown to black material and distinct from coincidental hemosiderin and lipochrome. Ultrastructural components of the pigmented tumors include melanosomes and premelanosomes. Two patients with pigmented tumors had associated von Hippel Lindau syndrome, and one had neurofibromatosis. The occurrence of melanin and melanosomes in pheochromocytoma has not been previously reported in the English literature. It is probably a reflection of the neural crest origin of this neoplasm. PMID- 8483888 TI - Immunocytochemistry in the differential diagnosis of effusions: use of logistic regression to select a panel of antibodies to distinguish adenocarcinomas from mesothelial proliferations. AB - Many studies have shown immunohistochemistry to be beneficial in discriminating between adenocarcinoma and mesothelial reactions in effusions. Although many of these studies suggest using a panel of antibodies, none of them used statistical methods to optimize their choice of assays. In the current study, stepwise logistic regression was applied to our data to select an appropriate panel of antibodies to differentiate between adenocarcinoma and all types of mesothelial proliferations. One hundred effusions (64 cases of adenocarcinoma, 27 cases of benign mesothelial proliferations, and 9 cases of malignant mesothelial proliferations) were analyzed for their reactivity with anti-EMA, anti-MFG, anti CEA, Leu-M1, B72.3, and the newly described epithelial membrane marker BER-EP4. An abbreviated panel consisting of anti-CEA, EMA, and B72.3 was shown to be sufficient in over 95% of our cases to accurately characterize a given effusion. When all three assays are negative, a diagnosis of adenocarcinoma is extremely unlikely, while when two or three of the assays are positive a diagnosis of adenocarcinoma is almost certain. The use of stepwise logistic regression has proven useful in the design of antibody panels as an adjunct to the differential diagnosis of effusions and may be applicable to the selection of panels in other diagnostic problems. PMID- 8483889 TI - Identification of Toxoplasma gondii in formalin-fixed, paraffin-embedded tissue by polymerase chain reaction. AB - We investigated the use of polymerase chain reaction (PCR) for diagnosis of toxoplasmosis in formalin-fixed, paraffin-embedded tissue, using seven cases in which the diagnosis was certain based on histologic examination and eight cases in which histologic findings only suggested Toxoplasma gondii infection. After amplification the PCR products were subjected to agarose gel electrophoresis followed by Southern blotting with a 32P-labeled oligonucleotide probe. In six of seven proven cases of toxoplasmosis, organisms were detected using DNA extracted from 1/50 to 3/50 of a 6-microns tissue section. In addition, organisms were detected in one of eight cases in which infection was suspected, but not proven by identification of organisms. We conclude on the basis of this study that PCR may be useful for detection of T. gondii in a few cases in which routine histologic examination or immunoperoxidase staining is not definitive. Since PCR has 1000-fold higher sensitivity when applied to fresh, rather than paraffin embedded, tissues, we expect PCR to be more sensitive in fresh tissue. PMID- 8483890 TI - p53 protein immunostaining in routinely processed paraffin-embedded sections. AB - Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human tumors. The altered protein product of the mutant gene is stabilized in tumor cells and can be detected using monoclonal antibody immunohistochemistry. We report a technique for immunostaining of the altered p53 protein in routinely processed paraffin-embedded tissue sections, comparing this method with a frozen section immunostain method for concordance. Similarly processed tumor cell lines with known mutations or deletions of the p53 gene served as positive or negative controls. The results in 25 human gliomas and 20 colorectal carcinomas showed a 100% correspondence of positive reactivity in the colorectal carcinomas and an 83% correspondence in the gliomas. In no case did the paraffin-embedded sections react in the absence of frozen section reactivity (that is, there were no false positives). Three of 18 gliomas showed reactivity in frozen sections without reactivity in the companion paraffin-embedded sections. This discrepancy could have been caused by technical factors such as length of fixation time. We propose that this new paraffin-embedded section immunostaining method will be of value as a screening technique for the investigation of p53 mutations in archived human tumors. The data thus obtained may then be correlated with clinical information and perhaps be of value in diagnosis or predicting outcome for various human cancers. PMID- 8483891 TI - RT-PCR detection of mRNA recovered from archival glass slide smears. AB - This manuscript describes a protocol for the utilization of glass slide preparations of hematologic specimens for the recovery of mRNA that is of a quality suitable for the reverse transcription-polymerase chain reaction (RT-PCR) detection of specific gene expression. Total cellular RNA obtained from archival bone marrow aspirate smears of 23 leukemia patients, which had been stored for periods of time from 1 day to 34 mo, were extracted, and 1 to 2 micrograms of each were subjected to RT-PCR using primer pairs specific for the amplification of beta-actin cDNA. Three pairs of primers for the amplification of beta-actin cDNAs of 83,260, and 540 base pairs were used to evaluate the length of mRNA that could be analyzed; the results indicate the consistent amplification of cDNA for the short- and intermediate-sized fragments as revealed by ethidium bromide fluorescence of agarose gel-resolved PCR products. To address the utility of RT PCR analysis towards the detection of mRNA associated with specific gene alterations in such specimens, a primer pair for amplification of the E2A-PBX1 fusion cDNA was used in PCRs of RT cDNAs for each of the 23 specimens, three of which were pre-B-cell acute lymphoblastic leukemias known to have the t(1;19) karyotype alteration resulting in the fusion of the E2A and PBX1 genes. Agarose gel electrophoresis analysis of the products of these RT-PCR amplifications revealed the amplification of the fusion gene cDNA in only those cases for which there was cytogenetic documentation of t(1;19); these results were confirmed by the Southern filter hybridization of an internal E2A-PBX1 oligonucleotide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483892 TI - Methods of radical prostatectomy specimen processing: a novel technique for harvesting fresh prostate cancer tissue and review of processing techniques. AB - Standard processing techniques for radical prostatectomy specimens uniformly require initial formalin fixation. Fresh prostate cancer tissue is needed for many types of prostate cancer research and may be needed for diagnostic purposes in the future. We describe a method for processing radical prostatectomy specimens that allows pre-fixation sectioning and harvest of fresh prostate cancer tissue. Because of increased difficulty interpreting capsular margin sections, however, we do not recommend it for routine use. We review other methods of radical prostatectomy specimen processing and provide an algorithm for their appropriate use. PMID- 8483893 TI - An immunocytochemical search for infectious agents in Crohn's disease. AB - Microorganisms have long been suspected of causing Crohn's disease (CD); however, an etiologic agent has yet to be identified. Few studies have employed immunocytochemistry (ICC) to examine tissue from patients with CD for microbial antigens. We investigated 36 formalin-fixed tissues from 16 patients with CD with ICC. No evidence of adenovirus, Borrelia, Brucella, BVDV, Campylobacter, Campylobacter-like organisms, Chlamydia, coronavirus, CMV, EBV, Legionella, mycobacteria, Pseudomonas, rotavirus, Salmonella, Shigella, staphylococci, Toxoplasma gondii, Treponema, or Yersinia was found. ICC identified E. coli and streptococcal antigens in 11 (69%) and 10 (63%) of the 16 cases studied, respectively. Escherichia coli immunoreactivity was located in ulcers, within the lamina propria, and along fissures. Streptococcal immunolabeling occurred within mucosal epithelial cells, in the lamina propria, in ulcers, along fissures, in granulomatous inflammation including multinucleate giant cells, and in lymph nodes. These results suggest that some of the granulomas in CD may result from immunologic processing of bacterial antigens following their penetration through a compromised mucosa. E. coli and streptococcal antigens may contribute to the pathogenesis of CD. PMID- 8483894 TI - Economic analysis of the clinical laboratory: labor implications. AB - Expenditures on laboratory tests have increased by 468% in real dollars in two decades although the cost per test has remained constant. Cost of labor has doubled over that period, with an approximately similar increase in personnel productivity as the offset. Part of the increased labor cost relates to increased pay for technologist work of apparent increased complexity. We found that technologists perceived less than 20% of all work and less than 4% of all tests performed to be highly complex or of moderately high complexity. Implications of these findings for test complexity analysis and for technologist training are discussed. PMID- 8483895 TI - Clear cell adenocarcinoma of the urinary bladder: report of a case of probable mullerian origin. AB - A 35-yr-old woman with a history of endometriosis and several recent episodes of hematuria was found to have an exophytic tumor arising from the mucosa of the posterior bladder wall. Microscopic examination showed a typical clear cell adenocarcinoma with a predominant tubulo-cystic pattern. A radical cystectomy was performed. Pathologic examination showed no residual tumor, but grossly visible intramural cysts at the site of the tumor had features of endometriosis on microscopic examination, strongly suggesting that the clear cell adenocarcinoma arose from endometriosis and was of mullerian derivation. Only one other adenocarcinoma of the bladder, an endometrioid adenocarcinoma, has had a probable mullerian origin. Although rare, these cases indicate that some vesical adenocarcinomas are of mullerian type. PMID- 8483896 TI - Intraluminal obstruction of distal ileum caused by a uterine leiomyoma. AB - A 64-yr-old woman with nausea, vomiting, abdominal pain, and fecal impaction was found at autopsy to have an ileal obstruction by an intraluminal, calcified, spiculated mass. Examination revealed that this calcified mass had the features of a uterine leiomyoma. We postulate that a calcified, pedunculated uterine leiomyoma formed adhesions with the distal ileum, eroded through the ileal wall, and came to rest in the bowel lumen. Here, it was partially digested by the flow of intestinal contents, freed from its pedicle, and ultimately created an ileal obstruction. This rare complication of uterine leiomyomas has not been previously documented. PMID- 8483897 TI - Evidence for covalent binding of acyl glucuronides to serum albumin via an imine mechanism as revealed by tandem mass spectrometry. AB - Acyl glucuronide metabolites of bilirubin and many drugs can react with serum albumin in vivo to form covalent adducts. Such adducts may be responsible for some toxic effects of carboxylic nonsteroidal antiinflammatory agents. The mechanism of formation of the adducts and their chemical structures are unknown. In this paper we describe the use of tandem mass spectrometry to locate binding sites and elucidate the binding mechanism involved in the formation of covalent adducts from tolmetin glucuronide and albumin in vitro. Human serum albumin and excess tolmetin glucuronide were coincubated in the presence of sodium cyanoborohydride to trap imine intermediates. The total protein product was reduced, carboxymethylated, and digested with trypsin. Six tolmetin-containing peptides (indicated by absorbance at 313 nm) were isolated by high-pressure liquid chromatography and analyzed by liquid secondary-ion mass spectrometry and collision-induced dissociation, using a four-sector tandem mass spectrometer. All six peptides contained tolmetin linked covalently via a glucuronic acid to protein lysine groups. Major attachment sites on the protein were Lys-195, -199, and -525; minor sites were identified as Lys-137, -351, and -541. Our results show unambiguously that the glucuronic acid moiety of acyl glucuronides can be retained within the structure when these reactive metabolites bind covalently to proteins, and they suggest that acyl migration followed by Schiff base (imine) formation is a credible mechanism for the generation of covalent adducts in vivo. PMID- 8483898 TI - Atomic force microscopy of biochemically tagged DNA. AB - Small fragments of DNA of known length were made with the polymerase chain reaction. These fragments had biotin molecules covalently attached at their ends. They were subsequently labeled with a chimeric protein fusion between streptavidin and two immunoglobulin G-binding domains of staphylococcal protein A. This tetrameric species was expected to bind up to four DNA molecules via their attached biotin moieties. The DNA-protein complex was deposited on mica and imaged with an atomic force microscope. The images revealed the protein chimera at the expected location at the ends of the strands of DNA as well as the expected dimers, trimers, and tetramers of DNA bound to a single protein. PMID- 8483899 TI - Actin is a surface component of calf pulmonary artery endothelial cells in culture. AB - An angiogenin binding protein isolated previously from endothelial cells has been shown to be a member of the actin family. Calf pulmonary artery endothelial (CPAE) cells were investigated for the presence of surface actin by immunoblotting of isolated surface proteins and by immunofluorescence. CPAE cell surface proteins were isolated by selective apical biotinylation and recovery of biotinylated proteins by avidin affinity chromatography. Immunoblotting with a specific smooth muscle alpha-actin antibody detected the presence of this type of actin among the isolated cell surface proteins. Immunofluorescence confirmed that smooth muscle alpha-actin is localized at the surface of nonpermeabilized CPAE cells. Exposure of CPAE cells to angiogenin prior to cell surface immunostaining diminished the signal. When CPAE and rat aortic smooth muscle cells were made permeable before staining, stress fibers could be recognized by the antibody in smooth muscle cells but not CPAE cells. The results indicate that a smooth muscle type of alpha-actin is localized specifically on the surface of cultured CPAE cells where it might interact with angiogenin and other actin binding proteins present in the extracellular environment. PMID- 8483900 TI - Assembly of cartilage collagen fibrils is disrupted by overexpression of normal type II collagen in transgenic mice. AB - Cartilage collagen fibrils, which are characterized by their thin, uniform diameters, are formed of a multicomponent system of three collagen types (II, IX, and XI) and interacting proteoglycans. We have used a genetic approach to test whether the proper assembly of this multiprotein structure was altered by overexpression of one of its normal components. Here we show that in transgenic mice in which the normal mouse alpha 1(II) collagen is overexpressed, thick abnormal collagen fibrils are generated. Mice that showed the highest expression of the transgene also displayed a larger proportion of abnormal fibrils and died at birth. We propose that an imbalance among the constituents of the cartilage collagen fibrils disrupts the mechanism that controls their assembly. The results show the applicability of the transgenic mice system to studies of complex multicomponent protein assemblies in intact animals. PMID- 8483901 TI - Predicting protein diffusion coefficients. AB - Diffusion coefficients for proteins in water are predicted. The numerical method developed is general enough to be applied to a wide range of protein surface shapes, from rodlike to globular. Results are presented for lysozyme and tobacco mosaic virus, and they are compared with actual data and with predictions made by less general methods. PMID- 8483902 TI - Synthesis of (1-->3), (1-->4)-beta-D-glucan in the Golgi apparatus of maize coleoptiles. AB - Membranes of the Golgi apparatus from maize (Zea mays L.) were used to synthesize in vitro the (1-->3), (1-->4)-beta-D-glucan (MG) that is unique to the cell wall of the Poaceae. The MG was about 250 kDa and was separated from a much larger (1- >3)-beta-D-glucan (callose) by gel-permeation chromatography. Diagnostic oligosaccharides, released by a sequence-dependent endoglucanase from Bacillus subtilis, were separated by HPLC and GLC. The trisaccharide beta-D-Glcp-(1-->4) beta-D-Glcp-(1-->3)-D-Glc, the tetrasaccharide [beta-D-Glcp-(1-->4)]2-beta-D-Glcp (1-->3)-D-Glc, and longer cellodextrin-(1-->3)-D-Glc oligosaccharides were synthesized in proportions similar to those found in purified MG. Activated charcoal added during homogenization enhanced synthesis of MG, presumably by removing inhibitory compounds. The Golgi apparatus was determined as the site of synthesis by a combination of downward and flotation centrifugations on sucrose step gradients. The rate of synthesis did not reach saturation at up to 10 mM UDP Glc. Chelators completely abolished synthesis, but synthase activity was restored by addition of either MgCl2 or, to a lesser extent, MnCl2. Synthesis continued for well over 1 h; addition of KOH to raise the pH from 7.2 to 8.0 during the reaction increased the rate of synthesis, which indicates that a transmembrane pH gradient may facilitate synthesis of MG. PMID- 8483903 TI - Long-term treatment of human immunodeficiency virus-infected cells with antisense oligonucleotide phosphorothioates. AB - The antiviral activity of antisense oligodeoxynucleotide phosphorothioates complementary to the tat gene, the gag mRNA, and the rev mRNA were studied in a long-term infection model. Three antisense oligonucleotides directed to the splice-acceptor site of the tat gene failed to suppress human immunodeficiency virus type 1 replication at 1 microM concentration in long-term culture. In contrast, two oligodeoxynucleotide phosphorothioates (28-mer) complementary to the gag and the rev mRNAs inhibited viral replication for > 80 days, and the antiviral activity was sequence- and length-dependent. In addition, after pretreatment of cells we could reduce the concentration of the antisense oligodeoxynucleotides by > 10-fold and still maintain the inhibition of viral replication. These results suggest that chemotherapy for human immunodeficiency virus type 1 infection with antisense oligodeoxynucleotide phosphorothioates may be achieved by an initial high-dose treatment followed by a lower maintenance dose. PMID- 8483904 TI - Glucose modulates the binding of an islet-specific factor to a conserved sequence within the rat I and the human insulin promoters. AB - In cultured rat and human pancreatic islets, glucose stimulated transcription of the rat insulin I gene through the mini-enhancer (FF) located between residues 196 and -247. The glucose-sensitive element was delineated to the region -193 to 227. The mini-enhancer bound islet nuclear proteins to form three major complexes (C1-C3). A 22-bp subfragment, spanning the sequence -206 to -227, was sufficient to retain all binding activities of the entire FF. The homologous sequence of the human insulin promoter interacted with rat islet nuclear extracts to form a single complex, corresponding to the C1 complex of the rat insulin I sequence. C1 was present only in insulin-producing cells; it was the major complex detected in isolated human islets with both rat and human insulin sequences. Furthermore, the DNA binding activity of the C1 factor(s) was selectively modulated by extracellular glucose in a dose-dependent manner; a 4.5-fold increase in binding intensity was detected when rat islets were incubated for 1-3 h in the presence of 20 vs. 1-2 mM glucose. We therefore suggest that the factor(s) involved in the C1 complex corresponds to the glucose-sensitive factor and, consequently, may play a determining role in glucose-regulated expression of the insulin gene. PMID- 8483905 TI - Initial localization of regulatory regions of the cardiac sarcolemmal Na(+)-Ca2+ exchanger. AB - We have analyzed the regulatory properties of the wild-type cardiac Na(+)-Ca2+ exchanger expressed in Xenopus laevis oocytes using the giant excised patch technique. The exchanger is activated by cytoplasmic application of chymotrypsin and exhibits a number of properties that can be changed or abolished by chymotrypsin treatment, including cytoplasmic Na(+)-dependent inactivation, secondary regulation by free cytoplasmic Ca2+, and inhibition by exchanger inhibitory peptide. Thus, the cloned exchanger expressed in oocytes exhibits regulatory properties similar to those of the native sarcolemmal exchanger. The exchanger protein contains a large (520 amino acids) hydrophilic domain modeled to be intracellular. The role of this region in exchanger function and regulation was examined by deletion mutagenesis. Mutants with residues 240-679 and 562-685 deleted exhibited exchange activity, indicating that this extensive region is not essential for transport function. Both mutants were stimulated by chymotrypsin treatment. Neither mutant demonstrated regulation by free cytoplasmic Ca2+ (Ca2+i) or inhibition by exchanger inhibitory peptide (XIP). However, mutant delta 562-685 but not delta 240-679 displayed Na(+)-dependent inactivation. The data suggest that the binding sites for XIP and regulatory Ca2+ may reside in the region encompassed by residues 562-685. A chimera made from renal and cardiac exchangers has normal regulatory characteristics and helps to further define these sites. PMID- 8483906 TI - Biochemical interaction of the Escherichia coli RecF, RecO, and RecR proteins with RecA protein and single-stranded DNA binding protein. AB - The Escherichia coli RecF, RecO, and RecR proteins were analyzed for their effect on RecA-mediated pairing of single-stranded circular DNA and homologous linear duplex DNA substrates. As shown by other workers, joint molecule formation by RecA was inhibited by E. coli single-stranded DNA binding protein (SSB) when it was added to single-stranded DNA before RecA. This inhibitory effect was overcome by the addition of RecO and RecR or RecF, RecO, and RecR. Both the rate and extent of joint molecule formation were restored to the maximal level observed when SSB was added after RecA. RecF, RecO, and RecR proteins had no effect on the conversion of joint molecules to final products and only appeared to stimulate an early step in the pairing reaction. The stimulatory effect of RecF, RecO, and RecR was not seen without SSB or when SSB was added after RecA. RecF protein by itself inhibited reactions in mixtures containing RecA and SSB, and this inhibition was overcome by the addition of RecO and RecR. These data suggest that RecO and RecR, and possibly RecF, help RecA overcome inhibition by SSB and utilize SSB-single-stranded-DNA complexes as substrates. PMID- 8483907 TI - A single protein catalyzes both N-deacetylation and N-sulfation during the biosynthesis of heparan sulfate. AB - Heparan sulfate is a highly sulfated carbohydrate polymer that binds to and modulates the activities of numerous proteins. The formation of these protein binding domains in heparan sulfate is dependent on a series of biosynthetic reactions that modify the polysaccharide backbone; the initiating and rate limiting steps of this process are the N-deacetylation and N-sulfation of N acetylglucosamine residues in the polymer. We now report that in the rat liver, biosynthesis of heparan sulfate utilizes a single protein that possesses both N deacetylase and N-sulfotransferase activities. This was accomplished by demonstrating that both activities resided in a purified soluble fusion protein containing the Golgi-lumenal portion of the enzyme. We propose that this protein be renamed the rat liver Golgi heparan sulfate N-deacetylase/N-sulfotransferase. PMID- 8483908 TI - Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. AB - Wound fluid was obtained from porcine partial-thickness excisional wounds and analyzed for heparin-binding growth factors. Two heparin-binding growth factor activities were detected, a relatively minor one that was eluted from a heparin affinity column with 0.65 M NaCl and a major one that was eluted with 1.1 M NaCl. These activities were not present in wound fluid 1 hr after injury but appeared 1 day after injury, were maximal 2-3 days after injury, and were not detectable by 8 days after injury. The heparin-binding growth factor eluted with 0.65 M NaCl was identified as a platelet-derived growth factor (PDGF)-like activity by the use of specific anti-PDGF neutralizing antibodies. The heparin-binding growth factor eluted with 1.1 M NaCl was shown to be structurally related to heparin binding epidermal growth factor (EGF)-like growth factor (HB-EGF) by several criteria, including binding to heparin affinity columns and elution with 1.1 M NaCl, competition with the binding of 125I-EGF to the EGF receptor, triggering phosphorylation of the EGF receptor, immunodetection on a Western blot, and stimulation of fibroblast and keratinocyte growth. It was concluded that HB-EGF is a major growth factor component of wound fluid and, since it is mitogenic for fibroblasts and keratinocytes, that it might play an important role in wound healing. PMID- 8483909 TI - Tandem double CC-->TT mutations are produced by reactive oxygen species. AB - Oxidative damage to DNA is mutagenic and thus may play a role in carcinogenesis. Because of the large number of different DNA lesions formed by oxidative species, no genetic alteration so far identified is exclusively associated with oxygen damage. Tandem double CC-->TT mutations are known to occur via UV damage to DNA and are thought to be a specific indicator of UV exposure. Using a sensitive reversion assay that can detect both single and double mutations within the same codon of the M13-encoded lacZ alpha gene, we show that treatments that produce reactive oxygen species can also produce tandem double CC-->TT mutations. The frequency at which these mutations occur is less than that for single base mutations by a factor of approximately 30. The induction of these mutations is inhibited by treatment that scavenges hydroxyl radicals. This unique mutation provides a marker of oxygen free radical-induced mutagenesis in cells that are not exposed to UV-irradiation and an indicator for assessing the involvement of oxidative damage to DNA in aging and tumor progression. PMID- 8483910 TI - Mice lacking major histocompatibility complex class I and class II molecules. AB - Mice lacking major histocompatibility complex (MHC) antigens were generated by mating beta 2-microglobulin-deficient, and therefore class I-deficient, animals with MHC class II-deficient animals. When housed under sterile conditions, the resulting MHC-deficient mice appear healthy, survive for many months, and breed successfully. Phenotypically, MHC-deficient mice are depleted of CD4+ and CD8+ T cells in peripheral lymphoid organs due to a lack of appropriate restricting elements. In contrast, the B-cell compartment of these animals appears intact, and MHC-deficient mice can mount specific antibody responses when challenged with a T-independent antigen. Spleen cells from MHC-deficient animals are poor stimulators and responders in a mixed lymphocyte reaction. Despite their relatively weak cellular immune responses in vitro, MHC-deficient mice reject allogeneic skin grafts with little delay, and grafts from MHC-deficient animals are rapidly rejected by normal allogeneic recipients. Taken together, these results emphasize the plasticity of the immune system and suggest that MHC deficient mice may be useful for examining compensatory mechanisms in severely immunocompromised animals. PMID- 8483911 TI - Histone H1 deposition and histone-DNA interactions in replicating chromatin. AB - An immunochemical method for analyzing protein interactions with BrdUrd substituted DNA was used to study binding of histones to nascent DNA in nuclei. The results indicate that in Ehrlich ascites tumor (EAT) cells, histone H1 deposits on newly replicated DNA simultaneously with or immediately after core histone deposition so that in chromatin replicated for 3 min, the stoichiometry of the histones is the same as in bulk chromatin. All histones, and especially histone H1, interact with nascent DNA more weakly than with bulk chromatin, although the efficiency of interaction via the globular domains seems to be the same for both types of chromatin. PMID- 8483912 TI - In vivo expression of mutant preproendothelins: hierarchy of processing events but no strict requirement of Trp-Val at the processing site. AB - Endothelin-1 (ET-1), a 21-residue vasoconstrictor peptide, originates in human cells from a 212-amino acid precursor (preproET-1). Big ET-1, an intermediate form of 38 amino acids, is generated by cleavage at basic-pair residues of proET 1, while a specific "ET-converting enzyme" was proposed to process the unusual Trp-Val site at positions 21 and 22 of big ET-1. We have previously shown that expression of synthetic RNA encoding human preproET-1 in Xenopus oocytes results in secretion of putative ET-1 and big ET-1. Here, to further dissect the processing pathway of preproET-1, we designed and expressed in oocytes a set of preproET-1 mutants. Four mutants affecting the Trp-Val site always originated putative ET-1(s) at levels comparable to the wild type, suggesting that there is only a conformational requirement for cleavage at this site. An Arg-->Ile mutation at the basic-pair site after the C terminus of big ET-1 fully inhibited the formation of both big ET-1 and ET-1, indicating that processing at this site is an early event and that big ET-1 is an obligate intermediate for the synthesis of ET-1 in vivo. Also, a truncated mutant bearing a stop codon after the C terminus of the big ET-1 sequence was totally stable and further processed into mature big ET-1 and ET-1, indicating that the second part of the precursor is not necessary for maturation. PMID- 8483913 TI - Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis? AB - Severe bloodstream-borne infection--i.e., sepsis--and the resulting multiorgan failure are now the most common cause of death in many intensive care units. One of the most fundamentally important and controversial issues concerning the pathophysiology of sepsis is the role of intracellular free calcium concentration ([Ca2+]i) in this disorder. Because of the critical role of calcium as an intracellular second messenger and as a potential cellular toxin, resolution of this issue is crucial. Using 19F NMR spectroscopy and the calcium indicator 5,5' difluoro-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate we demonstrate in the intact perfused organ, the rat thoracic aorta, that [Ca2+]i in aortic smooth muscle is increased > 2-fold during sepsis. Furthermore, we determined that sodium dantrolene, a drug that decreases release of calcium from the sarcoplasmic reticulum and that is lifesaving in malignant hyperthermia (a disorder due to increased [Ca2+]i), is able to reduce the elevated [Ca2+]i in sepsis to control values when added in vitro or when given in vivo to the animal. These results suggest that an increase in [Ca2+]i is an early event in sepsis and that increased [Ca2+]i may be responsible for, or contribute to, cellular injury. Dantrolene may offer a therapeutic strategy in the treatment of sepsis. PMID- 8483914 TI - Evidence from in vitro replication that O6-methylguanine can adopt multiple conformations. AB - The effect of O6-methylguanine (m6G) on replication, in a partially double stranded defined 25-base oligonucleotide, has been studied under nonlimiting conditions of unmodified dNTPs and over an extended time period, using the Klenow fragment of Escherichia coli DNA polymerase I. The sequence surrounding m6G has flanking cytosines (C-m6G-C), and the initial steady-state kinetics have been reported. When the primer was annealed so that the first base to be replicated was m6G, replication was virtually complete in approximately 5 min, although the reaction appears biphasic. When annealed with a primer where thymine or cytosine is paired opposite template m6G, about half the molecules were replicated in the first 15 sec, and no significant further replication was seen over a 1-hr period. When m6G was dealkylated by DNA-O6-methylguanine-methyltransferase, replication was rapid with no blockage. These data suggest that there can be two (or more) conformations of m6G. In these studies the term syn refers to conformers interfering with base-pairing, whereas anti refers to those allowing such base pairing. Previous physical studies by others indicate that syn- and anti conformers of the methyl group relative to the N1 of guanine are possible. Here molecular modeling/computational studies are described, suggesting that syn- and anti-m6G can be of similar energy in DNA, and, therefore, these two conformers may explain the two types of species observed during in vitro replication. An alternative explanation could be the possibility that the different species may manifest differential interactions of m6G with Klenow fragment. These results may provide a rationale for why m6G lesions in vivo have been reported to be lethal as well as mutagenic. PMID- 8483915 TI - Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is an important cause of sudden death in apparently healthy young individuals. In less than half of kindreds with HCM, the disease is linked to the beta-myosin heavy-chain gene locus (MYH7). We have recently described two missense MYH7 gene mutations [Arg-403 to Gln (R403Q) and Leu-908 to Val (L908V)] and found that the mutant message is present in skeletal muscle soleus) and that the mutant beta-myosin obtained from soleus muscle has abnormal in vitro motility activity. Having identified a second kindred with the R403Q mutation, and 3 other kindreds with two additional mutations (G741R and G256E), we performed histochemical analysis of soleus muscle biopsies from 25 HCM patients with one of these four mutations. Light microscopic examination of the NADH-stained biopsies revealed the presence of central core disease (CCD) of skeletal muscle, a rare autosomal dominant nonprogressive myopathy characterized by a predominance of type I "slow" fibers and an absence of mitochondria in the center of many type I fibers. CCD was present in 10 of 13 patients with the L908V mutation, 5 of 8 patients with the R403Q mutation, 1 of 3 patients with the G741R mutation, and 1 patient with the G256E mutation. Mild-to-moderate myopathic changes with muscle fiber hypertrophy were present in 16 patients. Notably, CCD was present in 2 adults and 3 children with the L908V mutation who did not have cardiac hypertrophy. In contrast, soleus muscle samples from 5 patients from 4 kindreds in which HCM was not linked to the MYH7 locus showed no myopathy or CCD. Soleus muscle biopsies from 5 control subjects also showed normal histology. This work demonstrates that (i) MYH7-associated HCM is often a disease of striated muscle but with predominant cardiac involvement and (ii) a subset of HCM patients with MYH7 gene missense mutations have CCD. PMID- 8483916 TI - Assembly of pericellular matrices by COS-7 cells transfected with CD44 lymphocyte homing receptor genes. AB - The capacity to assemble and retain a pericellular matrix is correlated with the expression of the cell surface binding sites specific for the extracellular matrix macromolecule hyaluronan. These binding proteins have been termed hyaluronan receptors. The lymphocyte-homing receptor CD44 may have identity with these hyaluronan receptors. To determine whether hyaluronan receptors function independently in this capacity for matrix assembly, mammalian cells were transfected with cDNA encoding the putative hyaluronan receptor CD44. After transfection with CD44 cDNA, COS cells gained the capacity to assemble hyaluronan dependent pericellular matrices in the presence of exogenously added hyaluronan and proteoglycan. Thus, CD44 receptors do function as matrix-organizing, matrix anchoring hyaluronan-binding proteins. In addition, the expression of CD44/hyaluronan receptors alone is sufficient to direct this matrix assembly. If matrix assembly is a function of cells in vivo that express hyaluronan receptors, this raises interesting possibilities for the role of the receptors in cell migration, when new extracellular matrix environments are encountered. PMID- 8483917 TI - Increasing the chemical potential of the germ-line antibody repertoire. AB - To augment the chemical potential of the immunological repertoire, a metal ion binding light chain has been introduced into the murine genome. Mice containing the transgene were subsequently immunized with a fluorescein conjugate. The transgenic light chain was found at a high frequency in the anti-fluorescein memory B-cell compartment. This general method should be applicable to other cofactors and small molecules and should lead to generation of antibodies with unique catalytic activities. PMID- 8483918 TI - Characterization of the rat neutral and basic amino acid transporter utilizing anti-peptide antibodies. AB - High-titer, site-specific antibodies have been produced against the rat kidney broad-spectrum, sodium-independent neutral and basic amino acid transporter (NBAA Tr) whose cDNA we cloned earlier. These antibodies have allowed us to characterize the transporter protein in normal rat tissues and in various cellular and in vitro expression systems. Western analysis detected 84- to 87-kDa glycosylated species enriched in rat renal and jejunal epithelial cell brush border membranes. In vitro translation of NBAA-Tr complementary RNA in the rabbit reticulocyte lysate system yielded a 78-kDa protein, a molecular mass that was predicted by the amino acid sequence deduced from the cloned cDNA. Translation in the presence of rough microsomal membranes yielded a glycosylated 89-kDa species. Glycosylated 87- to 89-kDa species were also expressed in Xenopus oocytes microinjected with NBAA-Tr complementary RNA and in COS-7 cells transfected with NBAA-Tr cDNA. Localization of NBAA-Tr in renal and intestinal brush border membranes is consistent with its proposed role in transepithelial transport of amino acids. PMID- 8483919 TI - Genetic and molecular characterization of a Notch mutation in its Delta- and Serrate-binding domain in Drosophila. AB - The Drosophila Notch gene product is a transmembrane protein that functions as a receptor of intercellular signals in several Drosophila developmental processes. Two other transmembrane proteins, encoded by the genes Delta and Serrate, genetically and molecularly behave as Notch ligands. All these proteins share the presence of epidermal growth factor (EGF)-like repeats in their extracellular domain. The Notch protein has 36 EGF-like repeats, 2 of which, numbers 11 and 12, are required for the interaction with the Delta and Serrate ligands. We have isolated and molecularly characterized a Notch mutation in its Delta- and Serrate binding domain that behaves genetically as both a Notch antimorphic and a loss-of function mutation. This mutation, NM1, carries a Glu-->Val substitution in the Notch EGF repeat 12. The NM1 allele interacts with other Notch alleles such as Abruptex and split and with mutations in the Notch-ligand genes Delta and Serrate. The basis for the genetic antimorphism of NM1 seems to reside in the titration of Notch wild-type products into NM1/N+ nonfunctional dimers and/or the titration of Delta products into nonfunctional ligand-receptor complexes. PMID- 8483920 TI - Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes. AB - Arachidonic acid (AA) has recently been shown to influence various cellular functions in the central nervous system. Here we report that AA increases, in a time- and concentration-dependent manner, 2-deoxy-D-[1-3H]glucose ([3H]2DG) uptake in primary cultures of astrocytes prepared from the cerebral cortex of neonatal mice. This effect is mimicked by an unsaturated fatty acid such as linolenic acid, while palmitic and arachidic acids, two saturated fatty acids, are inactive. Pharmacological agents that increase the endogenous levels of AA by stimulating AA release (melittin) or by inhibiting its reacylation (thimerosal) also promote [3H]2DG uptake by astrocytes. We also report that norepinephrine (NE) stimulates the release of [3H]AA from membrane phospholipids, with an EC50 of 3 microM; this effect is accompanied, with a temporal delay of approximately 4 min, by the stimulation of [3H]2DG uptake, for which the EC50 of NE is 1 microM. Since the cerebral cortex, the brain region from which astrocytes used in this study were prepared, receives a massive noradrenergic innervation, originating from the locus coeruleus, the effects of NE reported here further stress the notion that certain neurotransmitters may play a role in the regulation of energy metabolism in the cerebral cortex and point at astrocytes as the likely targets of such metabolic effects. PMID- 8483921 TI - Cell type-preferred expression of maize cab-m1: repression in bundle sheath cells and enhancement in mesophyll cells. AB - Different sets of genes for photosynthesis are expressed in mesophyll cells (MCs) and bundle sheath cells (BSCs)--the two adjacent but morphologically and functionally distinct types of photosynthetic cells in leaves of maize and other C4 plants. For example, light-harvesting chlorophyll a/b-binding proteins of photosystem II, which are encoded by a family of cab genes, are 3- to 4-fold more abundant in maize MCs than in BSCs. Each maize cab gene is different from the others in its relative expression in MCs vs. BSCs and in its degree of photoresponsiveness. The gene cab-m1 is positively photoregulated and is highly preferentially expressed in MCs. A 159-bp sequence in the 5' flanking region of this gene (-1026 to -868 relative to the translation start site) is required for MC-preferred expression of a reporter gene in greening maize leaves. Deletion as well as gain-of-function experiments have now shown that all of the sequence information required for MC-preferred expression resides within this mesophyll specifying region and that cab-m1 is preferentially expressed in MCs because of the presence of two types of sequence elements: one is required for suppressing expression in BSCs and the other for promoting expression in MCs. One of the four cis-acting regions mapped within the mesophyll-specifying region resembles the AT 1 box of some plant gene negative regulatory elements. Various combinations of such MC-specific enhancing and BSC-specific repressing regions could make maize cab gene family members different from one another in their relative expression in MCs vs. BSCs. PMID- 8483922 TI - Saturation mutagenesis of the human interleukin 6 receptor-binding site: implications for its three-dimensional structure. AB - Interleukin 6 is a 184-aa polypeptide postulated to belong to the class of helical cytokines. We built a three-dimensional model of human interleukin 6 based on the similarity of its hydrophobicity pattern with that of other cytokines and on the x-ray structure of growth hormone, interleukin 2, interleukin 4, interferon beta, and granulocyte-macrophage colony-stimulating factor. The resulting model is a bundle of four alpha-helices and suggests possible alternative conformations for the 9 C-terminal amino acids; in this region, the importance of Arg-182 and Met-184 for biological activity has been demonstrated [Lutticken, C., Kruttgen, A., Moller, C., Heinrich, P.C. & Rose John, S. (1991) FEBS Lett. 282, 265-267]. Therefore, we generated a large collection of single-amino acid variants in residues 175-181. Analysis of their biological activity in two systems and the receptor binding properties of a subset of the mutants indicates that the entire region is involved in forming the receptor binding surface and supports the hypothesis that this region does not assume an alpha-helical conformation. Remarkably, we also found a mutant with receptor affinity and biological activity much higher than wild type; the potential therapeutical value of this finding is discussed. PMID- 8483923 TI - Photoisomerization mechanism of the rhodopsin chromophore: picosecond photolysis of pigment containing 11-cis-locked eight-membered ring retinal. AB - The primary photochemical event in rhodopsin is an 11-cis to 11-trans photoisomerization of its retinylidene chromophore to form the primary intermediate photorhodopsin. Earlier picosecond studies have shown that no intermediate is formed when the retinal 11-ene is fixed through a bridging five membered ring, whereas a photorhodopsin-like intermediate is formed when it is fixed through a flexible seven-membered ring. Results from a rhodopsin analog formed from a retinal with locked 11-ene structure through the more flexible eight-membered ring (Ret8) are described. Incubation of bovine opsin with Ret8 formed two pigments absorbing at 425 nm (P425) and 500 nm (P500). P425, however, is an artifact because it formed from thermally denatured opsin or other proteins and Ret8. Excitation of P500 with a picosecond green pulse led to formation of two intermediates corresponding to photo- and bathorhodopsins. These results demonstrate that an appearance of early intermediates is dependent on the flexibility of the 11-ene and that the photoisomerization of P500 proceeds by stepwise changes of chromophore-protein interaction, which in turn leads to a relaxation of the highly twisted all-trans-retinylidene chromophore in photorhodopsin. PMID- 8483924 TI - Identification of a cell line that expresses a cell surface and a soluble form of the gp330/receptor-associated protein (RAP) Heymann nephritis antigenic complex. AB - gp330 is a large glycoprotein located in clathrin-coated pits at the surface of the glomerular and proximal tubule epithelia in the rat kidney. It was originally identified as the target of autoimmune antibodies in Heymann nephritis (HN) and has since been shown to be a member of the low density lipoprotein receptor gene family and to form a stable association with receptor-associated protein (RAP), which together constitute the HN antigen complex (HNAC). Progress in defining the normal functions of gp330 as well as the molecular mechanisms of HN has been hampered by the lack of an available kidney cell line that expresses this protein. We here report the identification of a rat yolk sac carcinoma cell line (L2) that synthesizes HNAC and expresses it in coated pits at the cell surface. gp330 and RAP from L2 cells are immunologically identical to their kidney counterparts, and peptide maps of gp330 yielded identical peptide fragments. Characterization of the cell line revealed that there are 3.3 x 10(4) gp330 molecules per L2 cell and that the cells produce a soluble form of gp330 that is released into the medium. Heparin ligand blot analysis demonstrated that RAP but not gp330 binds heparin. By heparin affinity chromatography, gp330 and RAP copurify, indicating that the glycosaminoglycan binding site within RAP is accessible when the subunit is complexed with gp330. These results indicate that the L2 cell line provides a valid and useful model for studies on the function of HNAC and the pathogenesis of HN. PMID- 8483925 TI - Body size, metabolic rate, generation time, and the molecular clock. AB - There is increasing evidence for variation in rates of nucleotide substitution among divergent taxonomic groups. Here, we summarize published rate data and show a strong relationship between substitution rate and body size. For instance, rates of nuclear and mtDNA evolution are slow in whales, intermediate in primates, and fast in rodents. A similar relationship exists for poikilothermic vertebrates. However, these taxa have slower mtDNA substitution rates overall than do homeotherms of similar size. A number of physiological and life history variables are highly correlated with body size. Of these, generation time and metabolic rate explain some patterns of rate heterogeneity equally well. In many cases, however, differences in metabolic rate explain important exceptions to the generation time model. Correlation between metabolic rate and nucleotide substitution may be mediated by (i) the mutagenic effects of oxygen radicals that are abundant by-products of aerobic respiration, and (ii) increased rates of DNA synthesis and nucleotide replacement in organisms with higher metabolic rates. Both of these factors increase mutation rate by decreasing the "nucleotide generation time," the average length of time before a nucleotide is copied either through replication or repair. Reconsideration of the generation time hypothesis to include physiological effects such as metabolic rate improves the theoretical underpinnings of molecular evolution. PMID- 8483926 TI - Coevolution of persistently infecting small DNA viruses and their hosts linked to host-interactive regulatory domains. AB - Although most RNA viral genomes (and related cellular retroposons) can evolve at rates a millionfold greater than that of their host genomes, some of the small DNA viruses (polyomaviruses and papillomaviruses) appear to evolve at much slower rates. These DNA viruses generally cause host species-specific inapparent primary infections followed by life-long, benign persistent infections. Using global progressive sequence alignments for kidney-specific Polyomaviridae (mouse, hamster, primate, human), we have constructed parsimonious evolutionary trees for the viral capsid proteins (VP1, VP2/VP3) and the large tumor (T) antigen. We show that these three coding sequences can yield phylogenetic trees similar to each other and to that of their host species. Such virus-host "co-speciation" appears incongruent with some prevailing views of viral evolution, and we suggest that inapparent persistent infections may link virus and most host evolution. Similarity analysis identified three specific regions of polyoma regulatory gene products (T antigens) as highly conserved, and two of these regions correspond to binding sites for host regulatory proteins (p53, the retinoblastoma gene product p105, and the related protein p107). The p53 site overlaps with a conserved ATPase domain and the retinoblastoma site corresponds to conserved region 1 of E1A protein of adenovirus type 5. We examined the local conservation of these binding sequences and show that the conserved retinoblastoma binding domain is characteristic and inclusive of the entire polyomavirus family, but the conserved p53-like binding domain is characteristic and inclusive of three entire families of small DNA viruses: polyomaviruses, papillomaviruses, and parvoviruses. The evolution of small-DNA-virus families may thus be tightly linked to host evolution and speciation by interaction with a subset of host regulatory proteins. PMID- 8483927 TI - Altered processing of Alzheimer amyloid precursor protein in response to neuronal degeneration. AB - In the brains of individuals with Alzheimer disease, senile plaques containing aggregates of beta-amyloid peptide, derived from the beta-amyloid precursor protein (APP), are seen in association with degenerating nerve terminals. It is not known whether the degenerating nerve terminals cause the formation of these aggregates or whether beta-amyloid peptide in the aggregates causes nerve terminal degeneration. In the present study of rat brain, degeneration either of local neurons or of nerve terminals caused decreased levels of a neuron-enriched isoform of APP, increased levels of a glia-enriched isoform of APP, and increased levels of potentially amyloidogenic, as well as nonamyloidogenic, COOH-terminal fragments of APP. Our results demonstrate that neuronal degeneration affects APP processing and suggest that it may contribute to amyloid formation in mammalian brain. PMID- 8483928 TI - Recombination sequence-binding protein in thymocytes undergoing T-cell receptor gene rearrangement. AB - Rearrangement of T-cell antigen receptor and immunoglobulin genes occurs in immature lymphoid cells by an unknown mechanism. To identify components of the rearrangement machinery, we isolated a population of murine thymocytes enriched for rearranging pre-T cells. In the nuclear fraction of these cells, we detected a protein that specifically bound the recombination sequences that flank T-cell receptor and immunoglobulin genes and are required for their rearrangement. This protein recognized both heptamer and nonamer motifs of the recombination sequence, separated by either 12 or 23 bp. The protein complexed with the recombination sequence oligonucleotide had an apparent molecular mass of 30 kDa. The binding characteristics of the protein and its presence in rearranging thymocytes and cell lines suggest that it could serve as the recognition unit of a recombinase complex. PMID- 8483929 TI - Gene inoculation generates immune responses against human immunodeficiency virus type 1. AB - Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue in vivo have been developed. In theory, gene inoculation should result in the production of antigenic proteins in a natural form in the immunized host. Here we present the use of such a technique for the inoculation of mice with a human immunodeficiency virus type 1 (HIV-1) envelope DNA construct (pM160). Mice were injected intramuscularly with pM160 and were subsequently analyzed for their anti-HIV envelope immune responses. Antisera collected from inoculated animals reacted with the recombinant HIV-1 envelope in ELISA and immunoprecipitation assays. The antisera also contained antibodies that were able to neutralize HIV-1 infection and inhibit HIV-1-mediated syncytium formation in vitro. Furthermore, splenic lymphocytes derived from pM160-inoculated animals demonstrated HIV-envelope-specific proliferative responses. The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents. PMID- 8483930 TI - Translation of mRNAs with degenerate initiation triplet AUU displays high initiation factor 2 dependence and is subject to initiation factor 3 repression. AB - The influence of the rare initiation triplet AUU on mRNA translation was investigated by comparing the activity of two pairs of model mRNAs that differ in the length of Shine-Dalgarno and spacer sequences. Irrespective of the initiation triplet (AUG or AUU), all mRNAs had similar template activity in vitro, but translation of AUU mRNAs depended more on initiation factor (IF) 2 and less on IF3 than that of AUG mRNAs. Increasing the IF3/ribosome ratio from 2 to 10 progressively inhibited the AUU mRNAs and abolished their capacity to compete for translating ribosomes with other mRNAs but did not affect activity of the AUG mRNAs. The effects induced by IF3 are from its different influence on on- and off rates of the transition 30S preinitiation complex<==>30S initiation complex; depending on the nature of the initiation triplet (AUG or AUU) of the mRNA, IF3 shifts the position of equilibrium toward binding or dissociation of fMet-tRNA, respectively. Stimulation of fMet-tRNA binding and dissociation yields superimposable IF3 titration curves that saturate at an IF3/30S ratio of approximately 1, indicating that the data are from the interaction of one molecule of IF3 with the same 30S binding site. Both effects are either lost or strongly reduced with 30S mutants defective in IF3 binding. Translational repression of AUU mRNAs by IF3 is from the factor-dependent dissociation of fMet tRNA from 30S subunits, which becomes relevant when excess IF3 interferes with the formation of 70S initiation complex, presumably by interacting with 50S subunit. PMID- 8483931 TI - Controlled release of polypeptides from polyanhydrides. AB - The effects of both polymer hydrophobicity and addition of stabilizers on the release and integrity of polymer-encapsulated proteins were studied. By using very hydrophobic poly[1,3-bis(p-carboxyhydroxy)hexane anhydride] with sucrose as an excipient, both recombinant bovine somatotropin and zinc insulin were released intact over 3 weeks. The released proteins appeared to maintain their integrity as judged by acidic reverse-phase HPLC, size-exclusion HPLC, radioimmunoassay, and conformation-sensitive immunoassays. Our results also suggest how polymer hydrophobicity can be used to enhance protein stability. PMID- 8483932 TI - Interaction of translation factor SELB with the formate dehydrogenase H selenopolypeptide mRNA. AB - The SELB protein from Escherichia coli is a specialized elongation factor required for the UGA-directed insertion of the amino acid selenocysteine into selenopolypeptides. Discrimination of the UGA codon requires the presence of a recognition element within the mRNA, which is located at the 3' side of the UGA codon; a hairpin structure can be formed within this mRNA region. By gel shift assays, a specific interaction between SELB and the mRNA recognition element could be demonstrated. Footprinting experiments, using nucleases or iodine as cleaving agents, showed that SELB binds to the loop region of the hairpin structure. In the presence of selenocysteinyl-tRNA, SELB formed a complex with the charged tRNA and the mRNA. The results indicate that targeted insertion of selenocysteine is accomplished by the binding of the SELB protein to this mRNA recognition element, resulting in the formation of a selenocysteinyl-tRNA.SELB complex at the mRNA in the immediate neighborhood of the UGA codon. PMID- 8483933 TI - Proposed atomic structure of a truncated human immunodeficiency virus glycoprotein gp120 derived by molecular modeling: target CD4 recognition and docking mechanism. AB - The atomic structure of a truncated glycoprotein gp120 from human immunodeficiency virus 1 (HIV-1) that contains the principal neutralizing antigenic sites and the CD4 binding domain has been derived by molecular dynamics and calculation of potential energy using the DREIDING force field. The resultant N-glycosylated molecular model is consistent with known properties of gp120 and docks with CD4 with a substantial reduction in the sum of the internal potential energies of the individual proteins (delta E = -200 kcal/mol). The primary mechanism of recognition and binding is the insertion of the solvent-accessible Phe-43 of CD4 into a gp120 solvent-accessible acceptor pit formed by Trp-427, Tyr 435, and the high-mannose oligosaccharide N-linked to Asn-230. delta E for the nonglycosylated complex is reduced significantly (-75 kcal/mol). Binding is by pi pi* interactions of the aromatic groups forming a hydrophobic, thermodynamically stable environment for these functional noncovalent bonding participants. This model for gp120 provides a theoretical basis for the evaluation of HIV molecular pathogenesis involving the env proteins, the analysis of conformation on functional immune response of the host, and the design of nonproteinaceous inhibitors specific for the CD4 binding site on gp120. PMID- 8483934 TI - Cloning and characterization of a fourth human somatostatin receptor. AB - We have isolated a gene coding for a fourth human somatostatin (somatotropin release-inhibiting factor) receptor. This additional somatostatin receptor (hSSTR4) is specifically expressed in human fetal and adult brain and lung tissue. The deduced amino acid sequence of the receptor displays both sequence and structural homology to three cloned somatostatin receptors as well as to other members of the family of GTP-binding-protein-coupled seven-helix transmembrane-spanning receptors. Pharmacological characterization of the expressed receptor reveals specific, high-affinity binding of somatostatin 14 and somatostatin 28. Surprisingly, several well-characterized synthetic somatostatin analogs fail to exhibit high-affinity binding to hSSTR4, indicating the existence of pharmacologically different receptor subtypes. Our data suggest that the diverse biological effects exerted by somatostatin are mediated by a family of receptors with discrete patterns of expression and different pharmacological properties. PMID- 8483935 TI - Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. AB - The binding of interleukin 2 (IL-2) to the IL-2 receptor (IL-2R) induces a rapid increase in tyrosine phosphorylation of cellular proteins. In a previous study, we have shown that p56lck (lck), a src-family protein tyrosine kinase (src-PTK), physically and functionally associates with the IL-2R beta chain (IL-2R beta). To further investigate a role of src-PTKs in IL-2 signaling, we analyzed a mouse pro B-cell line, in which lck is not expressed detectably. We observed that in this cell line, IL-2 induces activation of at least two src-PTKs, p59fyn (fyn) and p53/56lyn (lyn). Interestingly, stimulation of this cell line with IL-3 also induces activation of src-PTKs. The activation of fyn or lyn seems to be selective for stimulation with IL-2 or IL-3 since stimulation with IL-6 fails to activate them. Furthermore, we provide evidence for the physical association of fyn with IL-2R beta. Taken together with previous results, our current study suggests that different src-PTKs, each of which is expressed in a cell-type specific manner, can participate in the IL-2 signal transduction. PMID- 8483936 TI - Functional replacement of the hemolysin A transport signal by a different primary sequence. AB - Secretion of the 107-kDa hemolysin A (HlyA) from Escherichia coli is mediated by the membrane proteins hemolysin B and hemolysin D. Hemolysin B is a member of the so-called ATP binding cassette transporter superfamily, which includes the multidrug resistance P-glycoprotein, the cystic fibrosis CFTR protein, and the major histocompatibility complex-associated transporter of antigenic peptides. Recognition of HlyA by the hemolysin B/D transporter is dependent on a signal sequence mapped to the C-terminal 50 or so amino acids of the HlyA molecule. We show that the C-terminal 70 amino acids of leukotoxin from Pasteurella hemolytica can substitute functionally for the HlyA signal sequence. This 70-amino acid sequence contains no primary sequence similarity to the HlyA signal sequence; however, structural motifs of helix-turn-helix followed by strand-loop-strand can be deduced for both sequences. We also demonstrate by site-directed mutagenesis that changes to these predicted motifs affect transport function. It thus appears that the transport signal of HlyA may be defined by a higher-order structure and that the hemolysin transporter may recognize a much wider diversity of primary sequences than previously anticipated. This finding may have implications for understanding the basis of substrate specificity of other ATP binding cassette transporters. PMID- 8483937 TI - Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. AB - To identify the sites in the p53 tumor suppressor gene most susceptible to carcinogenic mutation by sunlight, the entire coding region of 27 basal cell carcinomas (BCCs) of the skin was sequenced. Fifty-six percent of tumors contained mutations, and these were UV-like: primarily CC-->TT or C-->T changes at dipyrimidine sites. Such mutations can alter more than half of the 393 amino acids in p53, but two-thirds occurred at nine sites at which mutations were seen more than once in BCC or in 27 previously studied squamous cell carcinomas of the skin. Seven of these mutation hotspots were specific to skin cancers. Internal cancer hotspots not located at dipyrimidine sites were not mutated in skin cancers; moreover, UV photoproducts were absent at these nucleotides. The existence of hotspots altered the process of inactivating p53 in BCC compared to other cancers: allelic loss was rare, but 45% of the point mutations were accompanied by a second point mutation on the other allele. At least one of each pair was located at a hotspot. Sunlight, acting at mutation hotspots, appears to cause mutations so frequently that it is often responsible for two genetic events in BCC development. PMID- 8483938 TI - Mapping the determinants of human immunodeficiency virus 2 for infectivity, replication efficiency, and cytopathicity. AB - Human immunodeficiency virus 2 (HIV-2) ISY and the newly derived HIV-2KR are infectious molecular clones that yield viruses differing markedly in their abilities to infect and/or induce syncytia in various T- and monocytoid-cell lines. Chimeric viruses were constructed from these two viral genomes to localize the genetic determinants of some of these properties. Envelope sequences, particularly those spanning the CD4 binding site, appear to be critical for the ability of HIV-2KR to infect MOLT-4 clone 8 and SupT1 cells and to efficiently infect the H9 cell line. On the other hand, multiple determinants may contribute to cytopathicity (gp41 and nef) in H9 cells and replication efficiency in monocytic (THP-1) cells. PMID- 8483939 TI - DNA sequencing: modular primers assembled from a library of hexamers or pentamers. AB - Here we report a striking effect displayed by "modular primers," which consist of hexamer or pentamer oligonucleotide modules base-stacked to each other upon annealing to a DNA template. Such a combination of modules is found to prime DNA sequencing reactions uniquely, unlike either of the modules alone. We attribute this effect in part to the increase in the affinity of an oligonucleotide for the template in the presence of an adjacent module. All possible pentamer (or hexamer) sequences total 1024 (or 4096) samples, a manageable size for a presynthesized library. This approach can replace the synthesis of primers, which is the current bottleneck in time and cost of the primer walking sequencing, and can allow full automation of the closed cycle of walking. PMID- 8483940 TI - Additivity of mutant effects assessed by binomial mutagenesis. AB - Eleven amino acid positions in the helix-turn-helix of lambda repressor have been mutagenized by using a combinatorial method in which alanine is substituted at each position with a probability of 0.5. Approximately 25% of the 2048 proteins in the resulting binomial library are active, including some variants with as many as seven alanine substitutions. The frequency of alanine substitutions in the set of active variants is a measure of the importance of the wild-type residue at each mutagenized position, and comparison of the frequencies of pairwise mutations with those expected based upon the single-position frequencies allows the additivity of mutant effects to be tested. For the positions examined here, we find that the effects of multiple substitutions are largely additive and are able to predict the activity class of the binomial mutants with 90% accuracy by using a model that simply sums penalty scores derived from the alanine substitution frequencies. We also find, however, that several residue pairs, including some that are distant in the three-dimensional structure, do display nonadditive effects that appear to be statistically significant. PMID- 8483941 TI - Low density lipoprotein- and high density lipoprotein-mediated signal transduction and exocytosis in alveolar type II cells. AB - Low density lipoproteins (LDL) and high density lipoproteins (HDL) from serum stimulate signal-transduction pathways and exocytosis in rat alveolar type II cells. Both LDL and HDL stimulated primary cultures of type II cells to secrete phosphatidylcholine (PtdCho), the major phospholipid component of pulmonary surfactant. The effects on secretion were preceded temporally by stimulation of inositol phospholipid catabolism, calcium mobilization, and translocation of protein kinase C from cytosolic to membrane compartments. Heparin, which blocks the binding of ligands to the LDL receptor, completely inhibited the effects of LDL on signal transduction and PtdCho secretion but did not inhibit the effects of HDL. Unilamellar PtdCho liposomes the size of native LDL had no effect on type II cells; however, PtdCho complexes containing either apolipoproteins E or A-I stimulated both signal transduction and PtdCho secretion. LDL receptors were present in type II cell membranes by immunoblotting. In contrast to findings with hepatic membranes, type II cells exhibited two major bands of 130 kDa and 120 kDa and a minor band at 230 kDa that also was present under reducing conditions. These results are consistent with our hypothesis that the LDL-receptor pathway functions in vivo to deliver cholesterol to type II cells and that this process is coupled to surfactant assembly and secretion via signal-transduction pathway(s). HDL elicits similar responses independent of the LDL receptor, suggesting that type II cells may use the selective uptake pathway to obtain cholesterol or that HDL triggers signal transduction by mechanisms unrelated to lipid delivery. PMID- 8483942 TI - Transmission-blocking activity of a chitinase inhibitor and activation of malarial parasite chitinase by mosquito protease. AB - During development in the mosquito midgut, malarial parasites must traverse a chitin-containing peritrophic matrix (PM) that forms around the food bolus. Previously Huber et al. [Huber, M., Cabib, E. & Miller, L. H. (1991) Proc. Natl. Acad. Sci. USA 88, 2807-2810] reported that the parasite secretes a protein with chitinase activity, and they suggested that parasite chitinase (EC 3.2.1.14) plays an important role in the parasite's egress from the blood meal. We found that allosamidin, a specific inhibitor of chitinase, completely blocked oocyst development in vivo and thus blocked malaria parasite transmission. Addition of exogenous chitinase to the blood meal prevented the PM from forming and reversed the transmission-blocking activity of allosamidin. Using exogenous chitinase, we also found that the PM does not limit the number of parasites that develop into oocysts, suggesting that the parasite produces sufficient quantities of chitinase to penetrate this potential barrier. In addition, we found that treatment of parasite chitinase with a diisopropyl fluorophosphate-sensitive trypsinlike protease from the mosquito midgut or endoproteinase Lys-C increased its enzymatic activity. These results suggest that malaria parasite has evolved an intricate mechanism to adapt to the PM and the protease-rich environment of the mosquito midgut. PMID- 8483943 TI - Three-dimensional structure of a human immunoglobulin with a hinge deletion. AB - X-ray analysis at 3.2-A resolution revealed that the Mcg IgG1 (lambda chain) immunoglobulin is a compact T-shaped molecule. Because of the hinge deletion, the Fc fragment lobe is pulled tightly upward into the junction of the Fab arms. Along the molecular twofold axis, the Fab arms are joined by an interchain disulfide bond between the two light chains. The antigen combining sites consist of large irregular cavities at the tips of the Fab regions. Potential complement (C1q) binding sites on Fc are sterically shielded by the Fab arms, but putative attachment sites are accessible for docking with the FcRI receptor on human monocytes and with protein A of Staphylococcus aureus. PMID- 8483944 TI - Associative learning potentiates protein kinase C activation in synaptosomes of the rabbit hippocampus. AB - Using electrophysiological, biochemical, and autoradiographic techniques, changes in protein kinase C (PKC) activity in specific regions of the hippocampus have been previously implicated in classical conditioning of the nictitating membrane response of the rabbit. Here we report that activation of PKC is potentiated 2- to 3-fold in synaptosomes of the hippocampal CA1 and CA2 to -3 regions in rabbits that have undergone classical conditioning of the nictitating membrane response. This potentiation is apparently due to a change in the biochemical properties of PKC within the synaptosomes and is not a result of an increase in total PKC activity. This observation correlates a subcellular biochemical change with classical conditioning of a mammal. PMID- 8483945 TI - Dexamethasone negatively regulates the activity of a chimeric dihydrofolate reductase/glucocorticoid receptor protein. AB - A chimeric gene was constructed encoding the entire murine dihydrofolate reductase (DHFR) protein with a carboxyl-terminal extension encompassing amino acids 494-795 of the rat glucocorticoid receptor (GR). The chimeric DHFR/GR gene encoded a functional DHFR protein, as measured by the ability to transform DHFR deficient Chinese hamster ovary (CHO) cells to a DHFR-positive phenotype. The DHFR/GR protein bound [3H]dexamethasone with a similar affinity as wild-type GR. Selection of stable CHO transformants in increasing concentrations of methotrexate resulted in increased expression of DHFR/GR. Addition of dexamethasone, a synthetic glucocorticoid agonist, decreased the activity of the chimeric protein, as measured by colony formation in selective medium, binding of fluoresceinated methotrexate, and direct enzymatic assay for DHFR. Addition of RU486, a glucocorticoid antagonist, antagonized the effect of dexamethasone. In the absence of dexamethasone, the chimeric protein was primarily localized to the cytoplasm. In the presence of dexamethasone or RU486, DHFR/GR translocated into the nucleus. However, RU486 did not decrease DHFR activity, distinguishing subcellular location from functional activity. These results demonstrate that glucocorticoids negatively affect the function of DHFR/GR. PMID- 8483946 TI - PutA protein, a membrane-associated flavin dehydrogenase, acts as a redox dependent transcriptional regulator. AB - The proline utilization (put) operon of Salmonella typhimurium is transcriptionally repressed by PutA protein in the absence of proline. PutA protein also carries out the enzymatic steps in proline catabolism. These two roles require different cellular localizations of PutA. Catabolism of proline requires PutA to associate with the membrane because reoxidation of the FAD cofactor in PutA needs the presence of an electron acceptor. Repression of the put operon requires PutA to bind to the put control-region DNA in the cytoplasm. The presence of proline, the inducer, is necessary but not sufficient for PutA to discriminate between its roles as an enzyme or as a repressor. Two conditions that prevent PutA protein binding to the put control region are (i) when proline and an electron acceptor or the cytoplasmic membrane are present or (ii) when PutA is reduced by dithionite. These two conditions increase the relative hydrophobicity of PutA protein, favoring membrane association and therefore enzymatic activity. PMID- 8483947 TI - Two Neurospora mitochondrial plasmids encode DNA polymerases containing motifs characteristic of family B DNA polymerases but lack the sequence Asp-Thr-Asp. AB - We have determined the DNA sequence of the mitochondrial plasmid from Neurospora intermedia strain Fiji N6-6. The plasmid contains a 1278-codon open reading frame that is 49% identical to the open reading frame of the mitochondrial plasmid from the LaBelle strain of N. intermedia, which is known to encode a DNA-dependent DNA polymerase. The results of polymerase assays and photolabeling studies, the high degree of identity with the LaBelle plasmid polymerase, and the observation that the Fiji polymerase activity in a reaction utilizing endogenous template is not affected by removal of RNA suggest that the Fiji plasmid also encodes a DNA dependent DNA polymerase. Comparison of regions of amino acids that are highly conserved in the two plasmid polymerases to family B polymerases reveals good correlates for the three major polymerase motifs and suggests that previously identified motifs characteristic of reverse transcriptase found in the LaBelle sequence are not significant. The polymerases encoded by the Fiji and LaBelle plasmids are unusual in that the amino acid sequence Asp-Thr-Asp, which forms the core of the third motif in family B polymerases, is not present in either Fiji or LaBelle. A version of the motif containing Thr-Thr-Asp exists in both sequences. PMID- 8483948 TI - Localization of the mRNA for a chicken prion protein by in situ hybridization. AB - The infectious agent (prion) responsible for transmissible spongiform encephalopathies in humans and animals is composed primarily of a 33- to 35-kDa glycoprotein called PrPSc (scrapie isoform of prion protein), which is a posttranslationally modified form of the normal cell-surface protein PrPC. Little is known about the function of PrPC. Interestingly, chPrP, the chicken homologue of PrPC, copurifies with a factor from brain that stimulates synthesis of acetylcholine receptors on skeletal muscle cells. Using in situ hybridization, we report here that chPrP mRNA is widely distributed in cholinergic and noncholinergic neurons throughout the adult central nervous system, including those in the telencephalic striata, thalamus and hypothalamus, optic tectum, medulla, cerebellum, and spinal cord. The mRNA is present in the brain and spinal cord as early as embryonic day 6 and is also found in dorsal root ganglia, retina, intestine, and heart. Our data suggest that if chPrP serves to regulate acetylcholine receptor number on postsynaptic targets, this is not its only function. It is likely that the protein plays a more widespread role in the central nervous system and perhaps elsewhere, possibly one related to intercellular communication, adhesion, or recognition. The chicken embryo represents an attractive experimental system in which to investigate the normal developmental function of PrPC. PMID- 8483949 TI - Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3. AB - A 39-nt DNA sequence, the interferon gamma (IFN-gamma) response region (GRR), is necessary for the IFN-gamma-induced transcription of the high-affinity Fc receptor for IgG (Fc gamma RI) and sufficient for the IFN-gamma-induced transcription of transfected plasmids. By using extracts from IFN-gamma-treated cells, three protein complexes will assemble in vitro on a 9-nt core region in the 3' domain of the GRR. The sequence of this core resembles the IFN-gamma activated sequence (GAS) described for the GBP gene. Mutations in this GAS core region prevent complex assembly and result in the loss of IFN-gamma induction of reporter constructs containing the mutation. In addition to the GAS core region, a 5' region of the GRR is necessary for optimal IFN-gamma induction and for formation of one of the DNA-protein complexes. By antibody reactivity, we show that a 91-kDa protein, first identified as a component of ISGF3, the IFN-alpha induced transcription complex, is present in at least two of the DNA-protein complexes. IFN-alpha can induce the formation of the faster-migrating 91-kDa protein-GAS complex but not the slower-migrating complex. Furthermore, IFN-alpha does not result in appreciable transcriptional activation of Fc gamma RI or constructs containing the GRR. Thus, these data demonstrate that the IFN-gamma activated 91-kDa protein is required for IFN-gamma induction of Fc gamma RI and suggest that an additional complex may be required for optimal expression and specificity. PMID- 8483950 TI - The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. AB - A method using PCR amplification and primer extension with fluorescent oligonucleotides was developed to analyze T-cell repertoires. The sizes of the hypervariable CDR3-like regions of the murine T-cell antigen receptor beta chains were measured for all possible V beta-J beta combinations. This analysis shows that beta chains are distributed into at least 2000 groups, a value that provides a lower limit to their complexity. The CDR3 sizes appear to be dependent on the J beta and especially the V beta segment used and correlates with amino acid sequence motifs in the corresponding CDR1 region. This feature of T-cell receptors is discussed. PMID- 8483952 TI - Let's get PREP up and running quickly. PMID- 8483951 TI - Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. AB - The intron sequences of the human L-type pyruvate kinase gene (PKLR) were determined by using primers selected from the known cDNA sequence. Oligonucleotide primers for these determined intron sequences were used to sequence the exons. When this technique was applied to the DNA of 10 unrelated patients with pyruvate kinase deficiency, the following eight different mutations in the coding region were detected: del391-393, A401, C464, G721, A1076, T1456, T1484, A1529. The A1529 mutation was found repeatedly in unrelated individuals, even in the homozygous state. The context with respect to a polymorphism at nt 1705 was compatible with a single origin for this mutation, and it may represent a balanced polymorphism. In normal subjects, five differences from the published cDNA sequence were documented. PMID- 8483953 TI - Which way out of the crisis? Coping strategies for dealing with cancer. AB - Following a diagnosis of cancer, patients are faced with the awesome challenge of responding positively to treatment and undertaking appropriate self-care. By offering patients support and encouraging their coping abilities, nurses can do much to improve their quality of life. PMID- 8483954 TI - Support can reduce the stress factor. Stress in neonatal nursing. AB - The emotional stresses involved in neonatal nursing are well-documented. By establishing support groups for nurses to discuss problem areas, the working environment of neonatal units can be made less stressful. PMID- 8483955 TI - A first step in effective communication. Providing a supportive environment for counselling in hospital. AB - Counselling is becoming an accepted part of the nursing process. Caring for sick and dying people, however, inevitably arouses feelings of sadness and failure. Learning to empathise rather than identify with patients can help prevent health professionals from perceiving illness and death as a personal failure. PMID- 8483956 TI - Preventive measures to maintain control. Management and treatment of vertigo. AB - Vertigo is a distressing problem which can leave sufferers feeling disorientated and lacking in confidence. There is much nurses can do to offer practical advice on how to minimise the risk of attack. PMID- 8483957 TI - Be alert to an avoidable problem. Management and prevention of antibiotic acquired diarrhoea. AB - Antibiotic-associated diarrhoea is an unpleasant and distressing problem for patients and health professionals alike. Although this condition can be treated with drugs, patient relapses are common. Implementation of rigorous infection control policies are therefore required. PMID- 8483958 TI - An audit of comfort and convenience. Comparison of oxygen mask and nasal catheter in the provision of postoperative oxygen therapy. AB - Postoperative oxygen therapy is most commonly administered either by an oxygen mask or a nasal catheter. An audit was, therefore, undertaken to assess the relative benefits of both forms of administration in terms of patient comfort and clinical efficacy. PMID- 8483959 TI - A case for emotional support and human contact. Management of cardiogenic shock. AB - 1. Cardiogenic shock is a state of acute circulatory failure precipitated by extensive left ventricular damage. 2. Nursing care of patients with cardiogenic shock must treat the 'whole person', and incorporate such elements as maintaining a safe environment; effective communication; nutrition and mobility. 3. Cardiogenic shock has a high mortality rate and is, therefore, very distressing for patients. Nursing care must ensure all patients are treated with respect and dignity. PMID- 8483960 TI - Assessment brings its own relief. Nursing care of individuals suffering from ischaemic leg pain. AB - Although pain has been the focus for much recent nursing research, little attention has been paid to relief of ischaemic leg pain. A structured and thorough assessment, which clearly identifies the pain experienced, and the use of analgesia and complementary methods of pain control can help reduce the chronic pain associated with this condition. PMID- 8483961 TI - How do inhaled bronchodilators work? AB - 1. Beta-agonists affect bronchodilation of the airways by their action on the bronchial smooth muscles. 2. Anticholinergic drugs affect bronchodilation of the airways by blocking the effect of acetylcholine and its bronchoconstrictor action. 3. Receptors are protein molecules found in cell membranes; they can selectively bind to messenger molecules and transduce a chemical signal into a response in a target cell. PMID- 8483962 TI - A barrier to continuity of care. Effects of the drug tariff on wound care in the community. AB - In light of the recent implementation of the Community Care Act, it is paradoxical that many products and dressings needed by community nurses are not available to them. This causes particular problems for patients discharged from hospital requiring continuity of wound care. What can be done to improve community nurses' access to the full range of products? PMID- 8483963 TI - The case for change. Implications of the 'Caring for People' White Paper. AB - The 1989 White Paper 'Caring for People' announced a radical shift in the way community care was to be delivered. The changes are now upon us and will affect all people with disabilities living in the community. They will also require nurses and social workers to work more closely together. PMID- 8483964 TI - Who cares about paediatric intensive care? PMID- 8483965 TI - Effects of calcium antagonists on K(+)-induced contraction in isolated aorta from diabetic and age-matched control rats. AB - The effects of nifedipine, verapamil and diltiazem on K(+)-induced contraction were investigated in isolated aortic rings from diabetic and age-matched control rats. Six weeks after streptozotocin injection there was no significant difference between the maximum isometric contraction to KCl (80 mmol/l), when expressed per milligram tissue weight, in aortic rings from diabetic rats and those from controls. A concentration-dependent inhibition of the K(+)-induced contraction was observed for the three Ca antagonists in aortic rings from both diabetic and age-matched control rats. Notably, the K(+)-induced contraction in aortic preparations from diabetic rats was more sensitive to nifedipine compared to control preparations (pD2: 8.61 vs. 8.31, p < 0.05), while no significant change in sensitivity towards verapamil (pD2: 6.99 vs. 6.92, p > 0.05) or diltiazem (pD2: 6.33 vs. 6.28, p > 0.05) could be demonstrated. Our data indicate a greater interference of nifedipine with voltage-operated channels in diabetic aortas compared with controls. Since a similar antispasmodic activity was found for diltiazem and verapamil it might be specific for dihydropyridine Ca antagonists. PMID- 8483966 TI - Effect of chronic treatment with losartan potassium (DuP 753) on the elevation of blood pressure during chronic exposure of rats to cold. AB - Elevation of diastolic, systolic, and mean blood pressures and cardiac hypertrophy occur in rats exposed to cold (5 degrees C) for 1-3 weeks. The renin angiotensin-aldosterone system is believed to play a role in the development of cold-induced hypertension since plasma renin activity increases within the first 2 weeks, presumably initiating the hypertensive process, and then returns to control level. The present study was designed to assess the role of angiotension II (Ang II) in the hypertensive process by chronic administration of losartan potassium, an Ang II1 receptor antagonist. Twenty-four rats were divided into four equal groups. After a 1-week control period, one group was kept at 25 degrees C while the remaining three groups were exposed to cold (5 degrees C). One of the cold-treated groups was untreated while the remaining two were given losartan in drinking water at a concentration calculated to provide 56 and 112 mg/kg/day. The untreated cold-exposed group had a significant elevation of systolic blood pressure within 1 week of exposure to cold. Losartan at both doses prevented the elevation of blood pressure and blocked both the dipsogenic and vascular responses to administration of Ang II. Exposure to cold increased food intake, urine output and water intake significantly above that of warm-adapted controls. Treatment with losartan tended to decrease each of these toward the level of controls. At the conclusion of the seventh week of exposure to cold, the rats were sacrificed and heart, kidneys, and brown fat removed and weighed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8483967 TI - Effect of methylene blue on blood pressure in rats. AB - Methylene blue (MB) is a soluble guanylate cyclase inhibitor, and known as an endothelium-derived relaxing factor (EDRF) inhibitor in vitro. In the present study, it was demonstrated that intravenous administration of MB caused a dose dependent hypertensive effect in rats. The hypertensive responses to the higher doses (10 and 20 mg/kg) of MB was followed by a reflex hypotension which did not appear in pithed rats. Noradrenaline depletion by reserpine pretreatment did not inhibit MB-induced hypertension, but abolished the hypotensive response. Both hypertensive and hypotensive phases were not altered by indometacin. These results may suggest that in vivo guanylate cyclase inhibition leads to an increase in blood pressure; prostaglandins and noradrenaline release from sympathetic nerve endings do not contribute to MB-induced hypertension and it may be due in part to the inhibition of EDRF. PMID- 8483968 TI - Production of 15-HETE by cultured smooth muscle cells from cerebral artery. AB - Hydroperoxyeicosatetraenoic acids (HPETEs) are potent vasoconstrictors which have been implicated in the pathogenesis of the delayed cerebrovascular spasm which follows subarachnoid haemorrhage. We have previously shown that one of their stable breakdown products, 15-hydroxyeicosatetraenoic acid (15-HETE), is the major lipoxygenase product released from isolated cerebral arteries. To investigate the vascular cell type responsible for their production we have established the culture of smooth muscle cells from cerebral arteries and have measured their release of HETEs upon stimulation with arachidonic acid. The cultured cells isolated from bovine cerebral arteries expressed smooth muscle phenotype as they stained positively for smooth muscle alpha-actin and not factor VIII-related antigen. Furthermore, these cells possessed the calcium and potassium conductances characteristic of smooth muscle cells. Upon incubation with arachidonic acid, the major lipoxygenase product was 15-HETE; no leukotrienes were detected. The formation of 15-HETE was concentration-dependent and was attenuated by nordihydroguaiaretic acid, but not by indomethacin. Similar to intact cerebral artery, cultured cerebrovascular smooth muscle cells have lipoxygenase activity, the major product of which is 15-HETE. These results are consistent with a possible role of the HPETEs in the pathogenesis of cerebral vasospasm. PMID- 8483969 TI - Inhibitory cholinergic effects of esaprazole on gastric secretion and plasma gastrin levels in the dog. AB - The effects of esaprazole, a novel antiulcer drug, on gastric acid secretion and plasma gastrin levels were investigated in dogs provided with a gastric fistula or Heidenhain pouch. Esaprazole affected in a different extent the tests performed on dogs with a gastric fistula. The greatest inhibitory effect was obtained against 2-deoxy-D-glucose-induced acid output and gastrin release. An intermediate inhibition by esaprazole was detected on bethanechol-evoked secretion, and the lowest activity was found versus histamine-stimulated secretion. All these responses were strongly inhibited by the antimuscarinic drug pirenzepine used as reference drug. Moreover, both esaprazole and pirenzepine prevented the acid secretory response to a test meal in dogs with a Heidenhain pouch, without significantly affecting plasma gastrin levels. The present results suggest that the depressant action of esaprazole on gastric secretion depends on its peripheral anticholinergic activity, consisting of a partial blockade of acid output and a main reduction of vagally mediated gastrin release. On the basis of these findings, the antiulcer activity of esaprazole might be in part ascribed to its inhibitory effects on gastric secretion. PMID- 8483970 TI - The NIH Strategic Plan: biomedical research as an investment for humanity. PMID- 8483971 TI - High intake of sweets late in the day predicts a rapid and persistent response to light therapy in winter depression. AB - Demographic characteristics, depression ratings, and detailed daily records of symptoms were examined as possible predictors of the response to light therapy of 51 patients with seasonal affective disorder. Of 26 items, high intake (> 1 portion) of sweets in the second half of the day was the best predictor of a rapid and persistent response to light therapy. The intake of sweets may either act on similar neurochemical substrates to those affected by light or provide a behavioral marker for individuals susceptible to light response. PMID- 8483972 TI - Lateral asymmetries in auditory acuity distinguish hallucinating from nonhallucinating schizophrenic patients. AB - Bilateral absolute auditory thresholds for frequencies ranging from 250 to 8000 Hz were examined on two occasions in schizophrenic patients and normal control subjects. Patients were classified as hallucinators and nonhallucinators on the basis of symptom ratings on both occasions. Previous evidence of better right than left ear acuity in schizophrenia was replicated but was found to characterize nonhallucinating patients only. Hallucinators showed no lateral asymmetry and inferior right ear acuity as compared with that in nonhallucinators. The results were reliable on retest. Brief Psychiatric Rating Scale scores of positive and negative symptoms in some cases differentiated hallucinators from nonhallucinators. The relationship of verbal hallucinations and right ear-left temporal lobe functions is discussed, together with complexities in cerebral laterality-syndrome relationships. PMID- 8483973 TI - Clozapine response and plasma catecholamines and their metabolites. AB - The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine. PMID- 8483974 TI - Treatment with clozapine and its effect on plasma homovanillic acid and norepinephrine concentrations in schizophrenia. AB - Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA), is an indirect tool to assess changes in dopamine turnover. Levels of pHVA have been reported to decrease during treatment with conventional antidopaminergic, neuroleptics, with the decrement correlating with symptomatic improvement in schizophrenic symptoms. Clozapine, an atypical neuroleptic, is the only drug proved to be effective in treatment-refractory patients. However, the mechanism mediating this unique efficacy has not been fully elucidated. This study examined the effect of clozapine on pHVA concentrations in schizophrenic patients. Since clozapine potently binds to alpha 2-adrenergic receptors, plasma norepinephrine (pNE) concentrations were also measured. Twenty-eight treatment refractory schizophrenic patients (24 men, 4 women) were treated with clozapine (up to 600 mg/day) for 5 weeks, after a minimum 1-week drug-free period. Symptomatology and pHVA and pNE concentrations were measured at the last drug free day and weekly for 5 weeks. Fourteen patients responded to clozapine treatment, while an equal number did not. Mean pHVA concentrations did not significantly change during treatment with clozapine. Although clozapine tended to lower pHVA concentrations in treatment responders, the effect was small and not significant. Clozapine treatment significantly raised pNE concentrations, but this did not differentiate responders from nonresponders to clozapine. These findings suggest that clozapine's effect on DA turnover is small and that clozapine may be effective in treatment-refractory schizophrenia by mechanisms other than, or in addition to, dopamine receptor blockade. However, since about one-third of NE is metabolized into HVA, the clozapine-induced increase in pNE may have overshadowed a possible lowering effect of clozapine on pHVA. PMID- 8483975 TI - The contribution of dream masochism to the sex ratio difference in major depression. AB - Twenty-five women and twenty-one men undergoing divorce had three laboratory nights of sleep on two occasions 1 year apart. On the third night, dream reports were elicited from subjects for each period of rapid eye movement (REM) sleep. Three groups differing on dream "masochism" were compared on personality, sex role, and social adjustment. Women "masochistic" dreamers had significantly higher scores on a scale of negative aspects of traditional feminine sex role identity than men or women without such dreams. They also showed less improvement at followup and had more need for emotional support. Dream masochism may be a continuing cognitive characteristic that contributes to the vulnerability of women to major depression. PMID- 8483976 TI - Factors of the Wisconsin Card Sorting Test as measures of frontal-lobe function in schizophrenia and in chronic alcoholism. AB - The purpose of this study was to examine the factor structure of the Wisconsin Card Sorting Test (WCST). The scores of 22 patients with schizophrenia, 20 patients with chronic alcoholism, and 16 normal control subjects were entered into a principal components analysis, which yielded three factors: Perseveration, Inefficient Sorting, and Nonperseverative Errors. WCST performance of seven patients with lesions invading the dorsolateral prefrontal cortex, available from another study, provided criterion validity for the Perseveration factor and, less strongly, for the Inefficient Sorting factor. Two patterns of performance characterized the three patient groups: the schizophrenic group and frontal lobe group had the highest Perseveration factor scores, whereas the alcoholic group had the highest Inefficient Sorting scores; the Nonperseverative Errors factor showed no significant group differences. Construct validity of these factors involved assessing, in all but the frontal group, the degree of overlap (convergent validity) and separation (discriminant validity) of each WCST factor with scores from tests of other cognitive functions. The convergent and discriminant validity of the Perseveration factor, but not the remaining two factors, received support only within the group of schizophrenic patients. PMID- 8483977 TI - Migraine and the eating disorders. PMID- 8483978 TI - No change in viscosity of lipid phase of RBC membrane in Alzheimer's disease. PMID- 8483979 TI - Fatigue scale lacks adequate validation. PMID- 8483980 TI - Spatial cognitive maps in animals: new hypotheses on their structure and neural mechanisms. AB - This article provides a hierarchical model of animal spatial cognitive maps. Such maps include both topological information, which affords loose, yet operational, representations of the connectivity of space and its overall arrangement, and metric information, which provides information about angles and distances. The model holds that maps can be initially described as a set of location-dependent reference frameworks providing directional information about other locations. The addition of an overall directional reference allows for the buildup of more complete (allocentric) representations. A survey of recent neurobiological data provides some hints about the brain structures involved in these processes and suggests that the hippocampal formation and the posterior parietal cortex would act differently by handling topological and metric information, respectively. PMID- 8483981 TI - TODAM2: a model for the storage and retrieval of item, associative, and serial order information. AB - This article presents an extended version of the convolution-correlation memory model TODAM (theory of distributed associative memory) that not only eliminates some of the inadequacies of previous versions but also provides a unified treatment of item, associative, and serial-order information. The chunking model extended the basic convolution-correlation formalism by using multiple convolutions, n-grams (multiple autoassociations of sums of item vectors), and chunks (sums of n-grams) to account for chunking and serial organization. TODAM2 extends the chunking model by including rn-grams (reduced n-grams), labels, and "lebals" (the involution or mirror image of a label) to provide a general model for episodic memory. For paired associates, it is assumed that subjects store only labeled n-grams and lebaled rn-grams. It is shown that the model is broadly consistent with a number of major empirical paired-associate and serial-order effects. PMID- 8483982 TI - Sexual strategies theory: an evolutionary perspective on human mating. AB - This article proposes a contextual-evolutionary theory of human mating strategies. Both men and women are hypothesized to have evolved distinct psychological mechanisms that underlie short-term and long-term strategies. Men and women confront different adaptive problems in short-term as opposed to long term mating contexts. Consequently, different mate preferences become activated from their strategic repertoires. Nine key hypotheses and 22 predictions from Sexual Strategies Theory are outlined and tested empirically. Adaptive problems sensitive to context include sexual accessibility, fertility assessment, commitment seeking and avoidance, immediate and enduring resource procurement, paternity certainty, assessment of mate value, and parental investment. Discussion summarizes 6 additional sources of behavioral data, outlines adaptive problems common to both sexes, and suggests additional contexts likely to cause shifts in mating strategy. PMID- 8483983 TI - Creation of prosody during sentence production. AB - Phrase-final words tend to be lengthened and followed by a pause. The dominant view of prosodic production is that word lengthening and pausing reflect the syntax of a sentence. The author demonstrates that, instead, lengthening and pausing reflect a distinctly prosodic representation, in which phonological constituents are arranged in a hierarchical, nonrecursive structure. Prosodic structure is created without knowledge of words' phonemic content. As a result, within a single sentential position, greater word lengthening necessitates shorter pauses, but across positions, word and pause durations show a positive correlation. The author presents a model of prosodic production that describes the process of prosodic encoding and provides a quantitative specification of the relation between word lengthening and pausing. This model has implications for studies of language production, comprehension, and development. PMID- 8483984 TI - Transitions in concept acquisition: using the hand to read the mind. AB - Thoughts conveyed through gesture often differ from thoughts conveyed through speech. In this article, a model of the sources and consequences of such gesture speech mismatches and their role during transitional periods in the acquisition of concepts is proposed. The model makes 2 major claims: (a) The transitional state is the source of gesture-speech mismatch. In gesture-speech mismatch, 2 beliefs are simultaneously expressed on the same problem--one in gesture and another in speech. This simultaneous activation of multiple beliefs characterizes the transitional knowledge state and creates gesture-speech mismatch. (b) Gesture speech mismatch signals to the social world that a child is in a transitional state and is ready to learn. The child's spontaneous gestures index the zone of proximal development, thus providing a mechanism by which adults can calibrate their input to that child's level of understanding. PMID- 8483985 TI - Primary error detection and minimization (PEDMIN) strategies in social cognition: a reinterpretation of confirmation bias phenomena. AB - A broad empirical literature demonstrates what has been termed a confirmation bias or positive test strategy heuristic in reasoning (Klayman & Ha, 1987), a potentially maladaptive pattern of data preferences that coexists with more normative preferences for highly diagnostic information (Skov & Sherman, 1986). A model is developed to account for these variations in test strategies, beginning with the premise that cognitive processes are adapted to reducing particularly costly errors rather than to detecting "truth" (Cosmides & Tooby, 1992). By specifying the information required to minimize various errors of primary concern, the model clarifies the adaptiveness of certain confirmatory preferences, identifies conditions under which such preferences should diminish, and outlines how error minimization goals might produce data preferences coincidentally consistent with normative prescriptions. PMID- 8483986 TI - The process of recurrent choice. AB - Recurrent choice has been studied for many years. A static law, matching, has been established, but there is no consensus on the underlying dynamic process. The authors distinguish between dynamic models in which the model state is identified with directly measurable behavioral properties (performance models) and models in which the relation between behavior and state is indirect (state models). Most popular dynamic choice models are local, performance models. The authors show that behavior in different types of discrimination-reversal experiments and in extinction is not explained by 2 versions of a popular local model and that the nonlocal cumulative-effects model is consistent with matching and that it can duplicate the major properties of recurrent choice in a set of discrimination-reversal experiments. The model can also duplicate results from several other experiments on extinction after complex discrimination training. PMID- 8483987 TI - McCollough effects as conditioned responses: reply to Dodwell and Humphrey. AB - P. C. Dodwell and G. K. Humphrey (1990) criticized the Pavlovian conditioning analysis of the McCollough effect, claiming that it was conceptually flawed and that it did not assign the McCollough effect any useful function. In this article, it is suggested that the error-correction interpretation that Dodwell and Humphrey proposed as an ostensible alternative to the conditioning interpretation can be subsumed by the conditioning interpretation. Furthermore, the conditioning interpretation does ascribe a useful function to the McCollough effect. PMID- 8483988 TI - Infectious diseases now. PMID- 8483989 TI - 'Healthy living' and sulphonylurea therapy have different effects on glucose tolerance and risk factors for vascular disease in subjects with impaired glucose tolerance. AB - This study was undertaken to determine whether impaired glucose tolerance and associated risk factors for cardiovascular disease can be improved with 'healthy living' by diet and exercise or with sulphonylurea therapy. Patients were recruited by screening subjects with either a family history of type II diabetes, previous gestational diabetes, or a previously raised plasma glucose (5.6-6.6 mmol/l). Impaired glucose tolerance was defined as hyperglycaemia on two separate tests, an achieved glucose level after a glucose infusion test above the 90th percentile of an age-matched normal population (> 9.3 mmol/l) or a fasting plasma glucose above the 95th percentile (> 5.6 mmol/l). Thirty-seven subjects with impaired glucose tolerance were entered into a randomized, prospective study for 6 months with allocations to healthy living or double blind to sulphonylurea (gliclazide 40 mg twice daily) or placebo tablets. The study took place in an out patient setting, with three times weekly exercise sessions at a Sports Centre. After 6 months the placebo group showed no change in plasma glucose, cholesterol and blood pressure. The subjects receiving gliclazide showed improved glucose levels (mean fasting plasma glucose levels fell from 5.8 to 5.1 mmol/l, p < 0.05) but no significant change in plasma cholesterol or blood pressure. The healthy living group, after exclusion of four non-compliant subjects, showed no change in glucose levels, but a decreased systolic blood pressure (fall in mean from 124 to 116 mmHg, p < 0.05) and plasma cholesterol levels (fall in mean from 5.2 to 4.5 mmol/l, p < 0.01). with an increase in HDL:LDL ratio (rise in mean from 0.39 to 0.46, p < 0.05). Subjects with impaired glucose tolerance may benefit in different ways from gliclazide and healthy living. The metabolic responses to each therapy may help to decrease the risk of developing diabetes and cardiovascular disease. PMID- 8483990 TI - Renal impairment with chronic hydrocarbon exposure. AB - Occupational hydrocarbon exposure is believed by some investigators to play an important role in the development of several non-neoplastic renal diseases. In view of the continuing debate in this area of nephrology we adopted a cross sectional approach by investigating the prevalence of clinical or sub-clinical renal dysfunction in subjects chronically exposed to hydrocarbons at their work site. Three groups of healthy men working in different and separate areas of a major car manufacturing plant in the North-west of England participated in the study. Group 1 comprised 112 paint sprayers with exposure to paint-based hydrocarbons, group 2 comprised 101 volunteers working in the transmission area of the plant with exposure to petroleum-based mineral oils, and group 3 comprised 92 automated press operators with minimal background exposure to lubricants who acted as internal controls. Early markers of renal dysfunction such as serum creatinine, urinary total protein, albumin, transferrin, retinol binding protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion were measured. Upper reference values of the parameters measured were derived from 105 comparable laboratory based controls with no occupational exposure to hydrocarbons or heavy metals. Group 1 had a significantly higher prevalence of elevated serum creatinine than the other groups and a higher prevalence of abnormal urinary total protein, N-acetyl-glucosaminidase, gamma glutamyl transferase, and leucine-amino-peptidase excretion than groups 2 and 3. Group 2 had normal serum creatinine but a significantly higher prevalence of abnormal urinary total protein, transferrin, retinol binding protein, N-acetyl glucosaminidase, and leucine-amino-peptidase excretion than group 3. Serum albumin was similar in all groups. There was some clustering of abnormal findings but the markers of renal dysfunction used in the study identified 37 individuals in group 1 and 31 subjects in group 2 with at least one abnormal parameter, compared to only five individuals in internal controls. This difference between the two target groups and group 3 was highly significant (p < 0.001). Subjects with chronic paint exposure had renal impairment and tubular dysfunction. Tubular dysfunction was also prominent with petroleum oil exposure. We therefore conclude that chronic hydrocarbon exposure may be associated with clinical and sub clinical renal dysfunction. We advocate careful monitoring of workers exposure to hydrocarbons and for more effective preventive measures. PMID- 8483991 TI - Respiratory involvement in primary muscle disorders: assessment and management. AB - Eighty-four patients with primary disorders of muscle were referred for assessment of respiratory insufficiency between 1978 and 1991. The eventual diagnoses were: 'limb girdle syndromes' (18 patients), adult onset acid maltase deficiency (14), dystrophia myotonica (13), inflammatory disorders (10), congenital myopathies (nine), rigid spine syndromes (five), dystrophies (Duchenne (six), facioscapulohumeral (four), Becker (one)) and miscellaneous (four). Presentations were often insidious, with progressive nocturnal hypoventilation culminating in respiratory failure or arrest, recurrent respiratory tract infections, or obstructive sleep apnoea. Respiratory symptoms developed relatively early in patients with acid maltase deficiency and inflammatory disorders but parallelled the development of limb weakness in limb girdle, myotonic and congenital syndromes. Sixty-six patients received respiratory support for a median of 5 years (1-34 years) using various techniques of negative and positive pressure ventilation. Fourteen patients received short-term support for an episode of respiratory failure before being weaned, 51 required nocturnal domiciliary ventilation and one was dependent on continuous domiciliary support. Tracheostomy was performed in 32 patients and used for domiciliary nocturnal ventilation in 25. Twenty-eight patients have subsequently died. PMID- 8483992 TI - Albendazole is effective treatment for chronic strongyloidiasis. AB - A total of 301 British ex-Far East prisoners of war, many of whom worked on the Thai-Burma Railway during World War II, consecutively attended The Liverpool School of Tropical Medicine for clinical review between January 1987 and August 1990. Fifty-two (17%) were found to have chronic strongyloidiasis. Diagnostic criteria included any of the following: characteristic larva currens rash, positive Strongyloides serology, and positive stool examination. Forty-seven were evaluable 6 months, after therapy with albendazole 400 mg twice daily for 3 days, which resulted in a 75% cure rate. Cure was defined as disappearance of the rash, if present, negative serology and negative stool examination. Patients who had more than one positive diagnostic feature were only considered cured if both or all had disappeared or become negative. All 12 of the patients in whom initial treatment failed were given a second course of albendazole: three further cures were obtained in eight evaluable patients. The overall cure rate was 81%. The only side-effects recorded were mild nausea and diarrhoea in one patient. We suggest that albendazole should be the treatment of choice for chronic strongyloidiasis. PMID- 8483993 TI - Thermoregulation and afterdrop during hypothermia in patients with poikilothermia. AB - The pathophysiology of afterdrop of core temperature during rewarming in patients with induced or accidental hypothermia remains controversial. We studied the effect of cooling and rewarming in four female patients with acquired poikilothermia and in four normal females. Exposure to cold air (16.5 degrees C) induced shivering and adequate vasoconstriction in normal individuals, without a fall in rectal temperature (Tr; 36.3 +/- 0.2 degrees C [mean +/- SD]); subsequent heating (40 degrees C) induced a rise in Tr to 37.0 +/- 0.3 degrees C and generalized sweating. The four patients all had spontaneous hypothermia (Tr 34.1 +/- 0.9 degrees C) before cooling. Tr decreased by 0.3-0.9 degrees C during cold exposure, and a marked afterdrop of Tr (0.3-0.5 degrees C) occurred during rewarming: this did not occur in normal individuals. Cooling failed to induce shivering and vasoconstriction in three patients. No patient showed visible sweating during heating despite a Tr of up to 38.0-38.5 degrees C and skin temperature of up to 37.7-38.5 degrees C. The basal metabolic rate was decreased by 71-82% in all patients during steady-state hypothermia and remained lowered during normothermia in two patients. We conclude that during hypothermia three of the four patients showed severe disorders of peripheral vasomotor function and shivering response. These data provide evidence for thermal conduction as the major mechanism of afterdrop during hypothermia. PMID- 8483994 TI - Comprehensibility of papers. PMID- 8483995 TI - Percutaneous transluminal renal angioplasty. PMID- 8483996 TI - The fine specificity of anti-GM1 antibodies. PMID- 8483997 TI - TNF in cerebral malaria. PMID- 8483998 TI - Lipids in cardiovascular disease. PMID- 8483999 TI - Cardiac arrest patient diverted by telemetry nurse. PMID- 8484000 TI - Hospital "self-insured": nurse's insurer liable. Case in point: Wake County Hosp. System v. National Casualty Co. (804 F. Supp. 2d 768--NC [1992]). PMID- 8484001 TI - Legal case briefs for nurses. WI: pharynx torn in fibe intubation attempts: res ipsa loquitur issue; OH: termination for sexual harassment: hospital policy conflicts with "at will" status. PMID- 8484002 TI - Death after E.R. treatment: proximate cause issue. Case in point: Godeaux v. Rayne Branch Hosp. (606 So. 2d 948--LA [1992]). PMID- 8484003 TI - Intracellular recordings from neurones of the submucous plexus. PMID- 8484004 TI - Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system. PMID- 8484005 TI - Integrated activity of cardiovascular and pain regulatory systems: role in adaptive behavioural responses. PMID- 8484006 TI - Mechanism and pathogenesis of ischemia-induced neuronal damage. PMID- 8484007 TI - CCK peptides and mRNA in the human brain. PMID- 8484008 TI - Effects of phenols on eicosanoid synthesis in A23187-stimulated human whole blood. AB - We have previously demonstrated that catecholamines have opposite effects on leukotriene (LT) and prostanoid synthesis. The aim of the present study was to test the effects of phenols (catechol, hydroquinone, phenol and resorcinol) on LTB4, LTE4 and thromboxane (TX)B2 synthesis in A23187-stimulated human whole blood. All tested compounds inhibited LTB4 and LTE4 synthesis. The IC50 values for catechol were 3 microM, 6 microM; for hydroquinone 4 microM, 3 microM; for phenol 285 microM, 226 microM and for resorcinol 180 microM, 902 microM. The compounds did not stimulate TXB2 synthesis but only inhibited it. The IC50 value for catechol was 3 microM, for hydroquinone 7 microM, for phenol 18 microM and for resorcinol 25 microM. Catechol and hydroquinone had hardly any effect on the LT/TX ratio. Phenol and resorcinol even increased the LT/TX ratio. The positions of hydroxyl groups of phenolic compounds are thus important for their actions on the LT/TX ratio. PMID- 8484009 TI - Tissue distribution, elimination and metabolism of [3H]-leukotriene C4 in the American bullfrog, Rana catesbeiana. AB - Tissue distribution, elimination, and metabolism of [3H]-leukotriene C4 were studied at 2.5 hours after injection in the conscious and anesthetized American bullfrog, Rana catesbeiana. Conscious frogs were injected via the dorsal lymph sac or the sciatic vein. Anesthetized frogs were injected via the abdominal vein. The organs containing the greatest percent of injected radioactivity at 2.5 hours after injection were liver, small intestine and kidney. Route of injection and anesthesia appears to alter distribution and elimination of leukotrienes. [3H] leukotrienes were eliminated into bladder water and bile. In addition, 7.8 +/- 2.2 and 5.2 +/- 2.5 percent of the injected radioactivity was found in the pan water bathing the ventral surface of the venously and dorsally injected conscious frogs, respectively, suggesting transfer of radioactivity across the skin. At 2.5 hours, polar metabolites represented 50% of the radioactivity found in liver, bile, and bladder water. These polar metabolites were determined to be 18-carboxy 19,20-dinor-leukotriene E4, 20-carboxy-leukotriene E4, and 20-hydroxy-leukotriene E4. Of the non-oxidized leukotrienes, bile contained mainly LTD4 while bladder water contained primarily LTE4. N-acetyl LTE4 was not detected in any samples. The tissue distribution, elimination and metabolism of leukotrienes in the bullfrog was similar to mammalian studies and suggests evolutionary conservation of leukotriene processing. PMID- 8484010 TI - 11-Dehydro thromboxane B2: a reliable parameter of thromboxane A2 production in dogs. AB - Plasma concentration of 11-dehydro thromboxane B2 (TxB2) is reported to be a reliable indicator of TxA2 production in human and rabbit. The purpose of this study is to examine whether we can use this parameter in dogs. The plasma concentration of 11-dehydro TxB2 was determined by enzyme immunoassay method using anti-11-dehydro TxB2 monoclonal antibody. When 10 micrograms/kg of TxB2 was intravenously administered to dogs in which endogenous production of prostanoids was blocked by aspirin, the plasma concentrations of 11-dehydro TxB2 before and 2, 5, 15, 60 min after TxB2 administration were 6.2 +/- 1.4, 54.2 +/- 5.0, 65.2 +/- 14.3, 65.2 +/- 16.4 and 31.0 +/- 7.5 pg/ml, while the corresponding TxB2 levels were 20.1 +/- 3.1, 3143.3 +/- 379.5, 1432.6 +/- 120.5, 356.8 +/- 38.9, and 128.9 +/- 13.6 pg/ml, respectively. Platelet-activating factor (PAF, 0.5 micrograms/kg) induced pulmonary vasoconstriction which was blocked by aspirin and OKY-046 (TxA2 synthetase inhibitor), indicating that TxA2 mediated this change. Plasma concentration of 11-dehydro TxB2 was increased by PAF. This change was also blocked by aspirin and OKY-046. These data suggest that the determination of plasma concentration of 11-dehydro TxB2 is useful to estimate the in vivo production of TxA2 in dogs. PMID- 8484011 TI - The enhancement by prostaglandin E2 of cumulus cell outgrowth in vitro. AB - Oocyte-cumulus cell complexes (OCCC) were aspirated from medium-sized (3-5 mm phi) porcine follicles to study quantitatively the process of forming monolayers. A monolayer index (MLI) was therefore developed. This index was evaluated by addition of graded quantities of fetal bovine serum. Furthermore, we observed that addition of prostaglandin E2 accelerated the monolayer formation (P < 0.001 at 20 hours versus 40 hours). The effect of PGE2 regarding both monolayer formation and cumulus cell expansion has been discussed. PMID- 8484012 TI - Prostaglandin F2 alpha stimulates inositol phosphate production in human pregnant myometrium. AB - We examined the effect of prostaglandin F2 alpha (PGF2 alpha) on phosphoinositide (PI)-hydrolysis in the outer layer of the human myometrium at the end of pregnancy. After pretreatment of myometrial explants with a cyclo-oxygenase inhibitor (indomethacin), the PGF2 alpha dose-response curve was shifted to the left and a maximal level of PGF2 alpha-induced IP accumulation was reached. In contrast, the well-known OT-induced IP accumulation was decreased in the presence of indomethacin, whereas potency was unchanged. Incubation of the myometrial explants with calcium-depleted medium, not only decreased the basal IP production but completely abolished the OT- and PGF2 alpha-induced IP accumulation. A L-type calcium channel inhibitor, verapamil 100 microM, significantly decreased PGF2 alpha-induced total inositol production whereas it had no effect on OT-response, suggesting that the first event of PGF2 alpha action is the activation of a calcium channel. These results point to marked differences in the mechanisms by which OT and PGF2 alpha exert their contractile effects in human myometrium at the end of pregnancy. PMID- 8484013 TI - Effects of lumbar epidural analgesia on prostaglandin F2 alpha release and oxytocin secretion during labor. AB - The concentrations of plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) were measured in 10 parturients with and 10 without lumbar epidural analgesia. A blood sample was taken immediately before analgesia and another 60 min later. The control patients were matched for the stage of cervical dilatation at the time of the first blood sample; the second was drawn 60 min later. Plasma PGFM decreased significantly after lumbar epidural anesthesia and increased in controls resulting in a highly significant difference between the groups (P < 0.005). Plasma oxytocin concentrations levels also changed in opposite directions in the two groups but the difference did not reach statistical significance (P < 0.1). Uterine activity increased in the controls and decreased in the analgesia group resulting in a significant difference between the groups (P < 0.05). All subjects delivered vaginally. The total duration of labor was longer in the analgesia group (7.8 +/- 1.0 h vs. 4.7 +/- 0.6 h; P < 0.05) as was the duration after analgesia (5.1 +/- 0.9 h vs. 2.5 +/- 0.8 h; P < 0.05), whereas the duration of the second stage was not significantly different. We conclude that lumbar epidural anesthesia results in suppression of PGF2 alpha release which may be the cause of the diminished uterine activity and the prolonged duration of the first stage of labor. PMID- 8484014 TI - Immunoactive iso-ANP/BNP in plasma, tissues and atrial granules of the rat. AB - We have developed a specific radioimmunoassay (RIA) for iso-rANP(1-45)/rBNP(51 95) using antiserum produced against a peptide comprise of the first 20 amino acid sequence of this cardiac hormone. Using this RIA, we found that atria contained the highest amount of iso-rANP(1-45) (567.37 pmol/g) which is about 140 fold higher than ventricles (4.32 pmol/g). With the exception of the lung and kidney, all other tissues had negligible amounts. The plasma level was 1.4 fmol/ml and the only molecular form found was the 45 amino acid form. HPLC analysis of extracts of isolated, purified atrial granules revealed that, like atrial natriuretic peptide (ANP), iso-rANP/rBNP is also stored in these granules. However, while ANP is stored predominantly as pro-ANP(1-126) and cleaved during or after release, iso-ANP/BNP is stored as the 45 amino acid form and may be processed prior to storage in the granules. PMID- 8484015 TI - Epidermal growth factor interferes with the effect of adrenaline on glucose production and on hepatic lipase secretion in rat hepatocytes. AB - We studied the interaction of epidermal growth factor (EGF) and adrenaline in the control of several metabolic functions in isolated hepatocytes from fed rats. EGF did not modulate glucose release, urea production or hepatic lipase secretion, but interfered with the stimulatory effect of adrenaline on both glucose and urea production and also with the inhibitory effect of this hormone on hepatic lipase secretion. EGF also interfered with the effect of both angiotensin II and vasopressin on glucose release and on hepatic lipase secretion. While the effect of EGF interfering with the action of adrenaline on glucose release was potentiated in the absence of extracellular calcium, the effect on the inhibition of hepatic lipase secretion was abolished. These results suggest that EGF interfered with catecholamine actions in the liver at a site distal from the generation of the calcium signal. PMID- 8484016 TI - Effect of water deprivation, desmopressin (DDAVP) infusion, and oral loads of water, Na+ and NH4+ on urinary excretion of epidermal growth factor in the rat. AB - Epidermal growth factor (EGF) is synthesized in the kidneys and excreted in urine. Administration of exogenous EGF modulates the reabsorption of Na+ and the vasopressin stimulated reabsorption of water in the collecting tubules. In order to clarify whether this reflects a physiological role for urinary EGF we examined the effects of changes in the oral loads of water, Na+ and NH4+ as well as the effect of infusion of the vasopressin analogue, desmopressin (DDAVP) on the endogenous urinary EGF excretion in the rat. Water deprivation for 48 h reduced the urinary excretion of EGF by 25% and the urinary EGF/creatinine ratio by 8%. Also, urinary volume, Na+ excretion, and urinary pH were reduced by water deprivation. Infusion of DDAVP, low plasma vasopressin induced by polydipsia, and changes in the renal excretion of Na+ and H+ did not affect the urinary excretion of EGF. IN CONCLUSION: it seems unlikely that nephrogenous EGF excreted in the urine plays a physiological role in the regulation of the renal excretion of Na+ and H+ and in the vasopressin stimulated reabsorption of water in the rat. However, since water deprivation reduced the urinary excretion of EGF it remains possible that urinary EGF plays a role in the complex physiological response to dehydration. PMID- 8484017 TI - Role of neurotensin in the regulation of exocrine pancreatic secretion in dogs. AB - A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg-1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 +/- 1.6 to 23 +/- 2.1 g 180 min-1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h-1 NT) fell from 22 +/- 1.9 to 7.5 +/- 0.8 g 180 min-1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 +/- 1.6 and 15.5 +/- 1.4 g 180 min-1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 +/- 1.9 to 7.1 +/- 7.1 +/- 0.9 g 180 min-1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism. PMID- 8484018 TI - PYY: a neuropeptide in the canine enteric nervous system. AB - This study re-examined the anatomical locations of PYY in the canine gastrointestinal tract. Immunohistochemical studies with two relatively selective PYY antisera demonstrated PYY-LI immunoreactivity in nerve cell bodies and nerve fibres in the intestinal and gastric myenteric plexus and the intestinal submucosal plexus and in nerve fibres of the intestinal deep muscular plexus. Immunoreactive PYY-LI was also present in ileal endocrine cells. All PYY-LI immunoreactivity was completely abolished by pre-incubation of the antibodies with synthetic PYY but was unaltered by pre-incubation with synthetic NPY. Individual synaptosomal preparations obtained from canine intestinal and gastric myenteric plexus, and intestinal deep muscular plexus and submucous plexus, contained considerable quantities of PYY-LI which, on reverse-phase HPLC, co eluted with a synthetic canine/porcine PYY standard. In contrast, isolated myenteric ganglia from rat and guinea pig did not contain detectable amounts of PYY-LI. These studies demonstrate that PYY is not confined to distal intestinal endocrine cells in the dog but is also an enteric neuropeptide with maximal concentrations being present in the intestinal myenteric plexus. PMID- 8484019 TI - In vivo modulation of gastrointestinal motor activity by Met-enkephalin, morphine and enkephalin analogs in chickens. AB - The main objectives of this work have been to study (1) whether or not opioid effects on gastrointestinal motility in chicken are mediated through central or peripheral pathways; (2) the receptors involved; (3) the correlation of the motor response to the distribution of Met-enkephalin in the gastrointestinal tract and (4) to evaluate the physiological role of endogenous opioids in spontaneous MMCs. Intravenous infusion of Met-enkephalin and morphine (5 x 10(-7) mol/kg) induced gastric inhibition and a migrating intestinal hyperactivity. Induced intestinal activity was faster in vagotomized chickens. In the stomach there was a correlation between the duration of the inhibitory response and the affinity of the agonists for mu-receptors ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO) > morphine > Met-enkephalin > Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE)). DPDPE induced duodenal hyperactivity which was not propagated. Immunohistochemistry showed that Met-ENK like material is mainly located at the myenteric plexus and the outer circular muscle in stomach. In the intestine, it was found in the myenteric and the deep muscular plexuses. When endogenous MMCs were studied, i.v. infusion of naloxone lengthened significantly their duration. In conclusion, the fact that Met-enkephalin and their analogs induced a migrating activity in the intestine and the lengthening of MMC by naloxone, suggest a physiological role for opioids on induction of MMC in birds, acting at peripheral level. PMID- 8484020 TI - Influence of glucagon-like peptide-1 on beta cell responsiveness. AB - The postulated incretin factor glucagon-like peptide-1 (GLP-1) causes a glucose dependent increase in insulin secretion from perifused rat islets. In the presence of 6 mM glucose the response to 10 nM GLP-1 is characterized by a large initial spike of secretion, followed by a brief, slowly rising phase. However, after 30-40 min of stimulation, this phase subsides to prestimulatory secretory rates. Raising the glucose level to 8 mM, however, amplifies and sustains the stimulatory effect of 10 nM GLP-1. The response to GLP-1 (10 nM) in the presence of 8 mM glucose is abolished by the metabolic inhibitor mannoheptulose (15 mM), and reduced by the calcium channel antagonist nitrendipine (5 microM), or the protein kinase C inhibitor of staurosporine (20 nM). A significant synergistic effect of GLP-1 (10 nM) and 10 microM carbachol, a cholinergic agonist, on insulin secretion was observed in the presence of 6 mM glucose. In the presence of either 6 or 8 mM glucose, GLP-1 (10 nM) has no significant effect on glucose usage or on inositol phosphate generation in [3H]inositol prelabeled islets. The results support the concept that GLP-1 may function as an important physiologic incretin factor, particularly when accompanied by agonists that activate phosphoinositide hydrolysis. PMID- 8484021 TI - Discussion paper: towards a systematic classification for regulatory peptides. AB - Advances in microsequencing technology have led to the elucidation of primary structures of peptidic messengers from many eukaryotic and prokaryotic life forms. Existing peptide nomenclature is based upon such factors as bioactivity, source of isolation (tissue or species), chemical attributes, acronyms derived from a combination of these factors, or by other arbitrary means. In order to overcome many of the problems arising from current nomenclature, a standardised classification scheme for peptidic messengers is proposed which utilises an alphanumeric code string analogous to EC enzyme classification to convey information on origin, chemistry and relatedness to other similar molecules. It is anticipated that the scheme outlined will provide the basis for the rational classification of new peptides. PMID- 8484022 TI - Physical injury risk versus risk from hazardous waste remediation: a case history. AB - This study was conducted to estimate the transportation risks associated with the removal of contaminated soils near the ASARCO copper smelter in Ruston, Washington. Three remediation options involving removal of differing amounts of soil were considered. The risks of death, disabling, and nondisabling injury were estimated. Under the scenario requiring the greatest soil removal, 3.62 disabling injuries, 14.46 possibly disabling injuries, and 0.67 deaths are expected to result from transporting the contaminated soil to an approved hazardous waste disposal facility. If the contaminated soil is not removed, the U.S. Environmental Protection Agency estimates that 2 arsenic-related skin cancers per 1000 lifetimes for exposed persons will occur. PMID- 8484023 TI - Birth defects, cancer, chemicals, and public hysteria. AB - The "media" consistently inform us of all the "things" that are dangerous to us. However, time/space constraints, along with lack of knowledge and understanding of the area, often lead to inaccurate and/or insufficient dissemination of information. The areas of cancer and birth defects are particularly misrepresented. Such dissemination of inaccurate/incomplete/misleading information has resulted in almost a state of hysteria. As a result, the public's perception of the role of chemicals in the incidences of cancer and birth defects is inconsistent with what has actually been documented in these areas. Although no one wants to be exposed to risks, people generally do not wish to be encumbered with unnecessary safety precautions. Thus, accurate information in the areas of carcinogenicity and teratogenicity should be documented in an effort to show how one can better assess the risks involved in work/home exposures to specific chemicals. A better understanding of how society perceives risk should enable one to better appraise the situation when confronted with information that could lead to "chemophobia." The consequences of misinformation about drugs and other synthetic chemicals have been particularly unfortunate with pregnant women: negligence in necessary drug use, unnecessary anxiety, and termination of planned pregnancies without reasonable cause. PMID- 8484024 TI - Food safety: are human activities really worse than nature's? AB - Those chemicals that are added to food during modern processing are most stringently examined for toxic effects and, if they demonstrate toxicity, are strictly controlled. Despite this, a considerable proportion of the North American human cancer burden has been associated with diet and nutrition. The possible contributions of excess calories, excess and wrongly balanced fats, natural contaminants, and naturally occurring carcinogens within the food supply to this horrendous burden of cancer is considered. The theoretically possible use of bioengineering techniques to modify the composition of food crops and thus to minimize the levels of carcinogens in the food supply is discussed. This is considered important since failure to monitor the effect of bioengineering may lead to an increase in the level of such noxious agents, especially if the goal of such bioengineering is to develop food crops with increased intrinsic resistance to pests and other spoilage organisms. PMID- 8484025 TI - Subsurface agricultural irrigation drainage: the need for regulation. AB - Subsurface drainage resulting from irrigated agriculture is a toxic threat to fish and wildlife resources throughout the western United States. Studies by the U.S. Department of the Interior show that migratory waterfowl have been poisoned by drainwater contaminants on at least six national wildlife refuges. Allowing this poisoning to continue is a violation of the Migratory Bird Treaty Act under U.S. Federal law. Critical wetlands and waterfowl populations are threatened in both the Pacific and Central flyways. The public is also at risk and health warnings have been issued in some locations. Subsurface irrigation drainage is a complex effluent containing toxic concentrations of trace elements, salts, and nitrogenous compounds. Some of the contaminants are classified by the U.S. Environmental Protection Agency (EPA) as priority pollutants and they can be present in concentrations that exceed EPA's criteria for toxic waste. The on-farm drainage systems used to collect and transport this wastewater provide point source identification as well as a mechanism for toxics control through the National Pollutant Discharge Elimination System (NPDES) permit process. A four step approach is presented for dealing with irrigation drainage in an environmentally sound manner. This regulatory strategy is very similar to those commonly used for industrial discharges and includes site evaluation, contaminant reduction through NPDES, and compliance monitoring. The EPA must recognize subsurface irrigation drainage as a specific class of pollution subject to regulation under the NPDES process. Active involvement by EPA is necessary to ensure that adequate controls on this wastewater are implemented. PMID- 8484026 TI - Infant formulas: evidence of the absence of pesticide residues. AB - Concern about the effect of potential pesticide residues on the safety of the U.S. food supply has led to extensive modeling and projections of worst-case scenarios. Many risk assessment models project risk based on an assumption of the presence of pesticide residues at the tolerance level or at a level equivalent to the limit of analytical detectability. Often, actual residue data, and the variability of analytical detection limits, are ignored in favor of simpler models. Data presented here demonstrate the absence of detectable levels of pesticides in infant formula. The range of detection limits of analytical methodology employed also are presented. A rationale for the absence of pesticide residues in infant formulas derived from plant and animal sources is presented which obviates worst-case scenario calculations of risk based on pesticide residue tolerance levels or method detection limits. PMID- 8484027 TI - Development and implementation of a safety evaluation program for chemical fibers. AB - Polyester and acrylic fibers often have prolonged contact with human skin: the sucking of childrens' toys may lead to ingestion. During manufacture, occupational exposure to fiber components may occur. An evaluation of these possible hazards was undertaken by data appraisal, chemical analyses, and animal plus human testing. Occupational exposure limits have already been set for the chemicals used in polymer manufacture. Finishing agents (applied to the fibers) were examined in bacterial mutation and rat acute oral toxicity tests. Finished fibers were tested for acute toxicity and then for sensitizing potential (on guinea pig skin). Human volunteer trials for skin irritance and sensitization followed. No adverse reactions were seen. Only when fibers were burnt was toxicity seen: smoke from acrylic fiber proved more toxic than that from polyester fiber (due principally to hydrogen cyanide release). Migration tests showed that little material leached out from the fibers: < 1 mg/dm2 surface area in saline, 0.4 mg/dm2 from acrylic fibers in methanol, 3.6 mg/dm2 from polyester fibers in chloroform. Analysis showed only fiber polymer components and finish in saline and methanol leachates. Whilst further testing may be required for areas of special concern, since only a limited range of biological endpoints have been addressed, it is concluded that current and foreseeable future uses of these chemical fibers pose little or no toxicological hazard. PMID- 8484028 TI - Chronobiology as it relates to toxicology, pharmacology, and chemotherapy. AB - Examples of circadian (daily) rhythms in man are presented and discussed. This is followed by presentation of experimental data indicating how the temporal organization affects the response of the host to potentially toxic agents, namely amphetamine and sodium pentobarbital. Data also are presented indicating that one unequivocally can improve therapeutic efficacy using the L1210 mouse leukemia model. This was accomplished by taking into consideration the circadian host toxicity response to anticancer agents, namely cytosine arabinoside, adriamycin, and cyclophosphamide. The subject monitored was the "cure rate" subsequent to treatment of different tumor loads. PMID- 8484029 TI - Health risk assessment. AB - In the United States the hazards posed by chemicals are often enormously exaggerated. In "calculating" risks of human cancer and establishing regulations, the United States Environmental Protection Agency makes a series of "conservative" assumptions that have no sound scientific basis. In consequence, trillions of dollars could be wasted. Exaggerations of risks are inherent in the procedures by which rodents are employed as stand-ins for humans. Dependence on results of maximum tolerated doses in the most sensitive strain or species of rodent is questionable. Important examples involve B6C3F1 mice, which in contrast to humans in developed countries, have a high control incidence of liver cancer. Those mice often respond with liver tumors when exposed to large doses of a substance. Other rodents are less often affected. Questionable assessments involving liver cancer in B6C3F1 mice include the risks posed by trichloroethylene, perchloroethylene, methylene chloride, butadiene, and phenobarbital. Spurious assessments for humans have also been noted when the male rat was the most sensitive animal. A unique mechanism in them gives rise to kidney tumors while female rats and male and female mice are not affected. PMID- 8484030 TI - Whither risk assessment? An overall perspective. AB - Major regulatory initiatives in health and safety are increasingly viewed as too costly, not objectively justified, and thus failing in their mandate to ensure a fair social distribution of rights and burdens. Official but arbitrary assumptions in cancer risk assessment and open-ended statutory language encourage regulatory agencies to overregulate. Also, institutional self-serving motivations of regulatory agencies add incentives to expand regulation. Mitigation of the current regulatory crisis may come from curbing these selfish incentives, and from requiring that regulation be justified on the basis of strict scientific standards of evidence, rather than on arbitrary assumptions and conjectures. PMID- 8484031 TI - Environmental health science research and human risk assessment. PMID- 8484032 TI - Toward a new national strategy on risk. PMID- 8484033 TI - Safety assessment of ingested heterocyclic amines: initial report. PMID- 8484034 TI - [On euthanasia]. PMID- 8484035 TI - [The descriptive and analytical epidemiology of traumatic spinal cord lesions occurring in Spain during 1984 and 1985]. AB - Descriptive and analytic epidemiology of traumatic spinal cord injury (Traumatic SCI) in Spain, with a sample of 33% of all incidental cases between 1984 and 1985, underlining the traffic accidents as the origin of those lesions. OR was obtained next of different variables of T-SCI, after controlling possible confusing factors through logistic regression and taking as "control group" Non Traumatic-SCI. OR in Traumatic-SCI decreases with age and in females. These Traumatic-SCI produce especially "cervical" lesions (OR = 3) and "complete" (OR = 4) with higher dependence on second persons. In the rest of variables there are no significative differences. PMID- 8484036 TI - [Endocarditis due to Candida albicans with peripheral arterial embolism and a cerebral mycotic aneurysm in an IV drug addict]. AB - Endocarditis due to Candida albicans (EC) is a rare cause of endocarditis in IV drug addicts (IVDA). Its diagnostic is usually difficult and high peripheral embolization is characteristic, and could affect big vessels. The case of a female patients (IVDA) 21 years old is discussed, who showed bilateral iliofemoral embolism and cerebral hemorrhage due to mycotic aneurysm breakage in a EC. These two complications appeared during an EC episode are exceptional. We insist in the importance of the echographic images in the suspicion diagnosis of EC. PMID- 8484037 TI - [Listeria monocytogenes infection in HIV patients: 2 new cases]. AB - Two new cases of infection due to Listeria monocytogenes in two females with HIV are discussed, one of them with full blown AIDS and the other pregnant and without knowledge of her seropositivity until that moment. Its clinical manifestation as a meningeal manifestation and bacteremia, coincide with the few cases described until now; different hypothesis invoked until now are reviewed to justify this infrequent association HIV-Listeria. PMID- 8484038 TI - [The current panorama of euthanasia in Spain]. AB - Due to the fact of the continuous advances of medical technology, physicians are able to prolong life even in those patients who suffer from a terminal illness to whom no hope to recover from it is left. Frequently the use or not of different therapies on these type of patients is questioned, who demand the autonomy over the self person to decide the cessation of a treatment. That is why it was proposed to investigate on the opinions and attitudes on the omission or cessation of treatments which could prolong life (passive euthanasia) or active euthanasia in terminal patients. A survey, which preserved the confidentiality of patients, was done in which 1,109 individuals took part coming from three different sectors of the population: hospital health professionals (physicians n = 346 and nurses n = 346) from San Carlos University Hospital, Madrid; students (n = 261) from Madrid Complutense University, and retired individuals (n = 156) from an elderly people club located at the Madrid province (Pinto). Sample was formed by 40% of males and 60% of females, with ages between 20 and 90 years. Most of the surveyed people agreed in certain circumstances or totally agree with omission or cessation of drugs which could prolong life (passive euthanasia) in terminal patients (70%). Regarding active euthanasia more than half (55%) opposed to it, 34% agreed in certain circumstances and 10% agreed completely. Significant differences were detected (p < 0.05) related to age, religious beliefs and political thoughts of the subjects. These results are compared to others already available. PMID- 8484039 TI - [Colonic tuberculosis]. PMID- 8484040 TI - [The epidemiological and diagnostic aspects of brucellosis]. PMID- 8484041 TI - [Wegener's granulomatosis: a case with fulminant presentation]. PMID- 8484042 TI - [Calcium, magnesium and asthma: apropos an incongruity]. PMID- 8484043 TI - [Severe pericardial effusion and skin metastases as the initial manifestations of a pulmonary epidermoid carcinoma]. PMID- 8484044 TI - [The effect of heparin treatment on the rose bengal test for Brucella]. PMID- 8484045 TI - [Primary psoas abscess]. PMID- 8484046 TI - [Septic thrombophlebitis of the portal vein]. PMID- 8484047 TI - [Visceral leishmaniasis in HIV-infected patients. A diagnostic criterion of AIDS?]. PMID- 8484048 TI - [The history and current status of lung transplantation]. PMID- 8484049 TI - [An overview of techniques for lung transplantation]. PMID- 8484050 TI - [Patient selection for lung transplantation from the aspect of surgery]. PMID- 8484051 TI - [Patient selection for lung transplantation from the aspect of internal medicine]. PMID- 8484052 TI - [Practice of the flow measurement using nonradioactive microspheres and X-ray fluorescence spectrometer]. PMID- 8484053 TI - [Characteristics of plasma levels of myosin light chain I in patients under aorta coronary bypass grafts]. AB - After cardiac operation plasma level of ventricular myosin light chain I (LCI), determined with monoclonal antibodies to myosin fragment, were studied in 30 patients under bypass surgery to assess its possible role as a marker for perioperative myocardial injury. LCI rapidly increased and reached peak levels (15.8 +/- 9.0 gn/ml; T-peak) at 88 +/- 28 minutes after aortic declamp (T-Time). Then LCI rapidly decreased with fast half-time disappearance (1.1 +/- 0.7 hours). In 7 out of 30 patients LCI improved to normal range and MB reached maximum levels (28.8 +/- 11.9 U/L) at 6.3 +/- 2.3 hours after declamp. No abnormal change was noted in ECG and no new defects were noted in T1-201 myocardial images. In the remaining 23 patients LCI decreased to minimum levels (4.1 +/- 2.1 ng/ml; min LCI) at 9.2 +/- 5 hours (min-Time) and then gradually increased to peak levels (8.4 +/- 5.8 ng/ml; M-peak, M-value) on day 3.3 +/- 1.0 (M-Time). MB reached maximum level (77.6 +/- 82.4 U/L, p < 0.1) at 3.4 +/- 1.4 hours (p < 0.001). Good correlation was noted among min-LCI, min-Time, M-value and summation of daily value of LCI (omega(LCI)) x min-LCI = 5.7-0.17 min-Time (r = -0.42) and M-value = 2.1 min-LCT(r=0.74) and omega(LCI) = -9.6 + 6.1 M-value (r = -0.96). From the rapid appearance of LCI peak levels after aortic declamp it was concluded that LCI, accumulated during aortic clamp, was washed out by aortic declamp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484054 TI - [An experimental study on transcoronary chemical ablation: comparison of ventricular tachyarrhythmias induced by chemical ablation according to different chemical materials]. AB - The purpose of this study was to compare heart rate, appearance rate and duration of ventricular tachycardia (VT) by transcoronary chemical ablation using 95% ethanol and 1% aethoxysclerol respectively. After the balloon which was guided to the left or right coronary artery with PTCA technique in anesthetized dogs was inflated, chemical ablation was performed using ethanol (n = 5) or aethoxysclerol (n = 5). These chemicals were administered at 0.05 ml/sec with total dose of 0.50 1.50 ml. A quadripolar electrode catheter was used to record the intracardiac electrogram. VT occurred in all dogs (100%) after the administration of both ethanol and aethoxysclerol. In one dog using ethanol, VT developed into ventricular fibrillation, resulting in death. In dogs using aethoxysclerol, the heart rate and duration of VT were significantly lower and shorter than in those using ethanol (p < 0.05). There were no significant differences determined histologically in the ablated lesions caused by these different chemicals. We conclude that the severity of VT induced in all subjects by chemical ablation is different according to the materials applied, and that aethoxysclerol seems to be safer in comparison with ethanol. PMID- 8484055 TI - [Linkage analysis in a Japanese long QT syndrome family]. AB - Romano-Ward syndrome is an autosomal dominant trait disease, which is characterized by QT prolongation and normal hearings and shows predisposal to sudden death from cardiac arrhythmia. Recently, Keating et al. reported that Harvey ras-1 locus (H-ras-1) was closely linked to long QT syndrome (LQTS), being located on the short arm of chromosome 11. In this study we have examined a three generation Japanese family whose members had recurrent fainting with prolongation of the QT interval on electrocardiogram. Using the H-ras-1 probe as DNA marker, we could not determine that the H-ras-1 gene was linked to LQTS. LQTS seems to be a genetically heterogeneous disease. Further study is needed to clarify the chromosomal location of the LQTS. PMID- 8484056 TI - [Coronary vasodilation during intracoronary injection of papaverine and acetylcholine in syndrome X: evaluation by coronary arteriograms and coronary venous oxygen saturation dynamics]. AB - To evaluate coronary vasodilatory reserve in syndrome X, left coronary arteriography and continuous measurement of coronary venous oxygen saturation (CSO2-Sat) were performed during intracoronary injection of papaverine (PAP) and acetylcholine (ACh) in 11 patients of syndrome X and 13 control subjects. Coronary diameter after PAP increased 10.2% in the control group and 9.8% in the syndrome X group, but after ACh decreased 1.7% in the control group and decreased 2.3% in the syndrome X group. These changes in coronary diameter by PAP and ACh in the two groups were not significantly different. However, coronary vasodilatory responses estimated by CSO2-Sat dynamics to ACh and to ACh/PAP were significantly lower in the syndrome X group than those in the control group (p < 0.05), although coronary response to PAP in the 2 groups was not significantly different. These findings suggest that endothelial-dependent vasodilation of coronary microcirculation is decreased in syndrome X. PMID- 8484057 TI - [A case of Buerger's disease solitary involved in the left subclavian and axillary artery]. AB - A 26-year-old male with about a ten-year history of smoking was admitted to our hospital for evaluation of ischemic symptoms including numbness, easy fatigability on exercise and lack of pulse in his left arm. His left axillary, brachial and radial pulse could not be palpated and a needle reaction was negative on physical examination. Laboratory data showed no diabetes mellitus or hyperlipidemia. C-reactive protein, Wassermann's reaction, rheumatoid reaction, anti-nuclear factor, anti-DNA antibody, hypocomplementemia and circulating immune complex were negative. Invasive arteriography using contrast medium revealed segmental occlusion with multiple collateral arteries showing a typical "corkscrew" appearance at the left subclavian artery. However, no stenotic and aneurysm-like lesions suggesting aortitis syndrome, vasculo-Bechet disease and giant arteritis were found on the aorta or other arteries including the pulmonary artery. Although no pathological study could be carried out, the angiographic and laboratory findings strongly suggested Buerger's disease as a possible cause of solitary stenosis of the left subclavian artery in this patient. PMID- 8484058 TI - [One family having 5 members with hypertrophic cardiomyopathy with similar pattern of left ventricular inflow and distribution of hypertrophy]. AB - We examined, in one family, 5 cases of hypertrophic cardiomyopathy (HCM) with a similar pattern of left ventricular inflow (LVIF) and distribution of hypertrophy. Its clinical background and significance were discussed. Because a variety of morphologic expressions of HCM may be observed in the same family, distribution of left ventricular hypertrophy (LVH) varies in even first-degree relatives of the family. In all five cases in this study, however, LVH was localized between the anterior wall and the interventricular septum. On the other hand, typical pattern of LVIF in HCM is "decreased peak velocity and prolonged deceleration time of the early diastolic wave (E), and compensatory augmentation of the atrial contraction wave (A)". All of the five cases in this study had a pattern of three characteristic peaks of LVIF, which showed the mid-diastolic wave between the E and A waves. The above findings suggested that the myocardial characteristics of the five cases in this family were very similar, and could be important clues clarifying the mode of inheritance of HCM. PMID- 8484059 TI - [ST-T changes associated with severe hypoxia in a case of obstructive sleep apnea syndrome]. AB - A 59-year-old man with obesity was admitted with nocturnal dyspnea and nocturnal precordial oppression. Catheter data disclosed no cardiac failure. Polysomnography was performed for a total of 3 nights. The diagnosis of obstructive sleep apnea syndrome was made because apnea index was 50 times/hour in average, the max apnea time was about 80 seconds and disappearance of airflow during decrease of endoesophageal pressure was observed. At the max apnea time, ST-T change in leads V2-5 was observed with severe desaturation (arterial oxygen saturation: 49%). It was considered that myocardial hypoxia following sleep apnea might be the cause of nocturnal precordial oppression. PMID- 8484060 TI - [A case of an idiopathic enlargement of the right atrium, lacking in prominent right atrium contour and mimicking left pericardial defect on the chest X ray]. AB - A 47-year-old man was admitted for evaluation of heart murmur in 1982. On admission, two-dimensional echocardiogram showed a giant right atrium with mild tricuspid regurgitation, but a chest X ray showed no prominent right atrium contour. Echocardiographic finding at various postures and chest X ray with artificial pneumothorax indicated little likelihood of left pericardial defect. An angiocardiogram and computed tomography showed the dilated right atrium with clockwise rotation. There was no indication of right atrial overload. Therefore, we made the diagnosis of an idiopathic enlargement of the right atrium. For about 10 years after discharge, we have followed up this patient. He has received no treatment and has been asymptomatic. On the other hand, echocardiography shows that the right atrium has gradually enlarged. Electrocardiogram has clearly revealed only a tall and slender peaked P wave in chest leads for the last 5 years. This may indicate not only an increasing load on the right atrium but also that the enlarged atrium is getting closer to the walls of the chest. We report this case of an idiopathic enlargement of the right atrium lacking in prominent right atrium contour, and mimicking left pericardial defect on chest X ray. PMID- 8484061 TI - [A case of percutaneous removal of a catheter fragment from the pulmonary artery using a long sheath]. AB - A case of successful removal of a catheter fragment from the pulmonary artery is reported. We employed the loop snare designed for transcolonoscopic polypectomy through a 9F long sheath. The sheath was advanced into the pulmonary artery over the balloon catheter. Handling of the loop snare was smooth and safe because of there being enough inner diameter of the sheath. Other instruments such as grasping-forceps or basket stone-catcher were also able to be advanced through the sheath. We recommend the employment of the 9F long sheath for retrieval of intravenous foreign bodies. PMID- 8484062 TI - [A case of successful tissue plasminogen activator in young-onset pulmonary embolism]. AB - A 16-year-old boy was admitted to the hospital because of chest pain, dyspnea, and syncope. Physical examination revealed blood pressure of 100/60 mmHg, regular pulse of 120 beats/min, and respiratory rate of 30/min. Pulsation of the right ventricle was palpable in the left margin of the parasternum. An increased second sound was audible in the second inter-costal lesion of the left subclavicle mid line. Results of blood tests were close to normal limits, except for slight leukocytosis and elevation of the LDH value. Analysis of artery blood gas showed hypoxia. The chest x-ray film showed cardiac enlargement. The value of systolic pulmonary artery pressure was estimated to be 47 mmHg by the cardiac echogram, which revealed enlargement of the right ventricle. Pulmonary embolism was suspected from the above findings. The value of pulmonary artery pressure was found to be 49/19 mmHg by Swan-Ganz catheter. Angiography of the pulmonary artery revealed filling defects of right in the right pulmonary artery. Tissue plasminogen activator was injected directly to the right pulmonary artery. After that, chest pain and dyspnea were relieved. In addition, arterial oxygen improved and pulmonary artery pressure decreased. At the 6th day after admission, the defect in the pulmonary artery angiography disappeared. Deep vein thrombosis of both femoral veins was recognized as a cause of pulmonary embolism by angiography of the femoral vein. PMID- 8484063 TI - [Obesity as a cardiovascular risk factor in Mexico. Study in an open population]. AB - We present the results of a population based study designed to estimate the prevalence of obesity defined as body mass index (BMI males > or = 27.7 kg/m and females > or = 27.31 kg/m) and to characterize the adipose tissue distribution pattern in our population, using subscapular and triceps skinfolds and waist and hip circumferences. In addition we assess the effect of obesity on the various metabolic indices that define cardiovascular risk, and explore the attitude of the participants towards obesity and its health consequences. The survey was performed in a low income neighborhood of Mexico City. Anthropometric measurements, laboratory determinations and protocol procedures used in the study were all performed according to international recommendations. The community had 4411 inhabitants, of whom 931 were age eligible (35-64 years): 452 (48.5%) men, 479 (51.5%) women. The response rate for the home interview was 91.7% and for the physical examination with interview and laboratory determinations it was 69.9%. The crude prevalence of obesity in men was 36.8% and in women 60.0%. Subscapular and triceps skinfold measurements were significantly higher in obese patients when compared to non obese participants. Adiposity tended to be distributed preferentially in the lower segment of the body, both in males and females. This pattern showed a tendency to reverse in the obese population. Fat distribution also showed a centrally predominant pattern, especially in obese males. In patients with obesity systemic blood pressure was higher than without obesity, though this was significant only in the first two age groups in males and the youngest age group in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484064 TI - Reliability of reference models for vital capacity in young Mexican males. AB - The reliability of 33 prediction models for vital capacity was assessed in university students living in Mexico City (altitude = 2,240 m). Forced vital capacity (FVC) was predicted and measured in 83 healthy male students, 18 to 30 years old and non-smokers. Spirometric tests were performed with a 9 liter bell spirometer, according to ATS guidelines. Mean measured FVC was 5,094 +/- 555 mL (BTPS) while mean predicted FVC by the models ranged from 3,700 mL to 5,350 mL (BTPS) with a small but significative correlation between actual and reference values (r = 0.398 to 0.474, p < 0.05). The residual standard deviation showed values from 503 to 577 mL which were similar to those seen in the original population. Although 11 of the 33 models were able to predict mean observed FVC by Dunnett's test (p < 0.05), all of them showed significant bias on the regression between measured values and residuals of predicted values, i.e. intercepts (2,435 to 4,127 mL), slopes (-0.61 to -0.87) and correlations (-0.59 to -0.95) were statistically different from zero (p < 0.01). Our data remark the need to obtain appropriate reference FVC values in young Mexican males due to the questionable predictability of the models tested. PMID- 8484065 TI - [Cytogenetic study of 22 adults and 3 children with acute lymphoblastic leukemia]. AB - Between 1987 and 1990 cytogenetic studies of bone marrow and lymphocytes from peripheral blood from 25 patients with de novo ALL were performed. All cases had chromosomal aberrations; however in 23 patients a normal cell line was also present. The most important structural aberrations found were: t(17;19)(q11;p13), t(2;9;22)(q34;q34;11), t(1;7)(p13;q33), t(6;11)(q26;p16), t(3;4)(q24-25;q26), t(1;12)(q23;q34), t(2;18)(q15;p12), t(2;4)(q23;q35) and t(4;11)(q21;q23). These chromosome abnormalities correlate with the response to treatment and survival and improve the identification of high-risk patients. Our study shows the presence of some chromosomal abnormalities different to those reported in the literature; however the breakpoints involved seem to be the same which suggests that these critical regions may be directly involved in the pathogenesis of these disorders. PMID- 8484066 TI - Image-guided fine needle aspiration biopsy. One year experience. AB - An analysis of one year experience with fine needle aspiration biopsies (FNAB) guided by computed tomography or ultrasound was conducted in a tertiary care reference center. We performed 66 procedures, two of them considered insufficient (97% technical success). The overall sensitivity was 90% and the specificity 100%. There were five false negative and no false positive results. The cytological diagnosis was confirmed with core biopsy of surgical specimen (available in 30 patients, 47%), discharge diagnosis and/or clinical evolution. Twenty seven patients had a positive FNAB for malignancy. The complication rate was 12%, all of them considered as minor complications which resolved with conservative management. There was a concordance between FNAB results and final diagnosis in 91.5% of the cases. Fine needle aspiration biopsy is a very useful diagnostic procedure if performed adequately. PMID- 8484067 TI - [Thyroid nodule. Study of 88 cases]. AB - We present a prospective study of 88 patients with thyroid nodules seen in our institution in 1985-86 and the results of a 5 year follow up. The algorithm for resolution among different therapeutic options was established in regard to the clinical characteristics, imaging and particularly the histopathologic studies. Their age ranged from 18 to 79 years; 94% of the patients were females. Most of the nodules were solid (69%) and measured 1-4 cm in diameter. The image of 62% of the thyroid scans was of a non-functioning nodule and 13% were hyperfunctioning. In 80% the ultrasonographic pattern was solid or mixed. Surgery was undertaken in 19 patients (21%). In 58%, a diagnosis of malignancy was established. The biopsy (aspiration and tru-cut) suggested the presence of the malignant tumors when taken together in 90% of the cases. Hormonal treatment was given to 62 patients; in 40-45% of them there was a significant reduction in the size of the nodule. Aspiration and sclerosis of cystic nodules were performed in 19 patients with significant shrinkage in 82%. Radioactive iodine was used in 11 patients. Our algorithm reduces costs and precludes unnecessary morbidity in patients with thyroid nodules. PMID- 8484068 TI - [Histoplasma capsulatum in the peripheral blood of patients with AIDS. Report of 4 cases with an increase of lactate dehydrogenase]. AB - This paper describes the clinical course of four patients with AIDS who were found to have H capsulatum in peripheral blood. The evolution of the infection was fulminant and all died within the first 96 hours following hospitalization. In every case the presence of the characteristic mycelium and "tuberculate" macroconidia of Histoplasma was established in cultures. All cases showed the hematological abnormalities common in other AIDS associated diseases. In addition, there was an increase in serum lactic dehydrogenase over ten times our normal level: the lowest LDM assay was 2137 IU/mL and the highest 4839 IU/mL. This clinical course resembling septicemia and the demonstration of H capsulatum in a peripheral blood smear has had a rate of 12% in our experience (four out of the 34 cases of AIDS with histoplasmosis seen in our institution from January 1984 to March 1991). PMID- 8484069 TI - Diffuse small lymphoplasmacytic lymphoma of the GI tract associated with massive intestinal amyloidosis. AB - We report the case of an 80 year old man who developed a small diffuse lymphoplasmacytic lymphoma that involved the entire gastrointestinal tract. The malignant lymphoma was associated with intestinal amyloidosis presumably produced by the neoplastic lymphocytes. The outstanding symptoms were asthenia, fever, marked weight loss, diarrhea and melena. The postmortem study disclosed, in addition, lymphomatous infiltration to the gallbladder, mesenteric lymph nodes and testis. The case represents an exceptionally widespread type of diffuse gastrointestinal lymphoma. PMID- 8484070 TI - [Allogenic bone marrow transplant]. PMID- 8484071 TI - [Flow cytometry in the immunotyping of acute leukemias]. PMID- 8484072 TI - [Regarding the article "Adjuvant chemotherapy in gastric cancer. Experience at the National Institute of Nutrition"]. PMID- 8484073 TI - Management of vitamin B12 deficiency in outpatient care. PMID- 8484074 TI - Rape victims--assaults, injuries and treatment at a medical rape trauma service at Oslo Emergency Hospital. AB - OBJECTIVE: To describe assaults, injuries, and treatment in the 168 patients who attended the medical rape trauma service in 1987. To give an impression of the medico-legal documentation that is required. DESIGN: Prospective study. SETTING: A rape trauma service (RTS) established at the Emergency Hospital in Oslo. The service is free, open around the clock, and independent of police notification. RTS has standardized the medico-legal report used for rape victims. PARTICIPANTS: All patients attending RTS from 1 January to 31 December. RESULTS: Eighty-two (49%) patients reported the incident to the police. Two-thirds of the patients were assaulted by strangers, one-fifth by two or more assailants, and 16 were subjected to attempted rape. Weapons were used in 50 of the assaults. Eighty-one patients had physical injuries requiring documentation but no special treatment. Fourteen patients were infected with sexually transmitted diseases, three patients became pregnant. Seventy-eight patients returned for a medical follow up. As many as 128 patients (76%) needed care from all parts of the emergency medical and psycho-social services. CONCLUSION: RTS shows that primary health service can be responsible for the treatment of rape victims and for the medico legal documentation of rape trauma. PMID- 8484075 TI - Reference values for 24-hour non-invasive ambulatory blood pressure: a population study of men aged fifty. AB - All 50-year-old men (N = 126) living in a defined neighbourhood were invited to undergo 24-hour ambulatory, non-invasive blood pressure (BP) monitoring. The participation rate was 90%. Seven per cent of the subjects were taking antihypertensive drugs and 19% had a current diagnosis of hypertension or had been so diagnosed sometime previously. The 5th, 50th, and 95th percentiles of the subjects' ambulatory BP are presented. On average, daytime, night-time, and 24 hour ambulatory BP were 135/86, 114/68, 128/80 mmHg, respectively, and the average casual BP was 137/86 mmHg. The ambulatory BP in the present study was higher than in previous reference studies. No attempt was made to select the stratified subjects according to casual BP or any other medical or social variable. This and a high participation rate probably account for the difference in ambulatory BP vis-a-vis those found in other reference studies. PMID- 8484076 TI - Computer-based simulation model for evaluation of variations in practice patterns of general practitioners: a feasibility study. AB - Our study aimed at developing a computer-based simulation model for the consultation process in general practice. The model was developed in the computer language COM-CATS and makes use of an IBM-compatible personal computer with an automated diasprojector attached. A feasibility study comprised 122 general practitioners (108 male and 14 female), participating in the 6th Nordic Congress of General Practice (Aarhus, Denmark, 1989). All participants were given a short introduction to the patient and his symptoms, but all further information was optimal and selected by the doctor. There was a large variation in practice patterns of the general practitioners. Their actions were, however, performed selectively, i.e. a few tests were requested by most doctors and none of the doctors performed large numbers of tests. The great advantage of the computer model in research into clinical decision-making is that it allows for a standardization of the clinical situation, gives the doctor an opportunity to select between optional information, and permits an automatic gathering of huge amounts of information about the decision-making process. PMID- 8484077 TI - Why we need a new clinical method. PMID- 8484078 TI - Use of primary medical care: does place of residence play a role? AB - The present paper is based on a prospective study of the use of primary health care in the municipality of Forde in 1988. The population of about 8,300 could easily be divided into two groups: semi-urban and rural. We wanted to investigate whether there were differences in the use of primary medical care between the two groups. The empirical study showed higher total contact rates for the rural women than for the semi-urban women, and virtually no difference among the men. The semi-urban population was more apt to use direct contacts and had more frequent contacts for new health problems than the rural population. Higher age and female gender were associated with more use of all types of and all reasons for contact. In multivariate analyses, a number of interaction effects between age, sex, and place of residence were demonstrated. PMID- 8484079 TI - Frequent attenders in general practice: a study from Slovenia. AB - To compare frequent with infrequent attenders at GPs' surgeries in a rural area in Slovenia with respect to morbidity, type of contact with the GP, referral pattern and the prescriptions given, a random sample of 623 records from a population-based register was analysed retrospectively. The frequent attenders had a higher proportion of contacts for malignant disease, mental disorder, and gastrointestinal disease. They also had a greater probability for a "superficial contact", were more likely to be referred to a specialist, were less likely to receive a psychotropic drug, and were more likely to receive a prescription for an antibiotic. We conclude that there are differences in morbidity between the two groups. The high referring pattern and the high proportion of "superficial contacts" of the frequent attenders may reflect poor doctor/patient relationship of this group. PMID- 8484080 TI - The intensity and variability of symptoms in dyspepsia. AB - During the waiting time for upper gastrointestinal endoscopy 165 patients with dyspepsia completed a questionnaire and a diary for daily measurements of the symptoms pain, heartburn, and global complaints. 23 patients (14%) had peptic ulcer disease (PUD), 18 oesophagitis (11%), and the rest were labelled nonulcer dyspepsia (NUD). NUD was further subdivided into ulcer-like, reflux-like, dysmotility, and essential NUD by means of predefined symptom profiles. 39 (24%) patients were on H2 receptor antagonist treatment. In general, the intensity of the daily symptoms was rather low, and except for a higher rating of heartburn in oesophagitis, there were no significant differences between PUD, oesophagitis, and NUD--treated or untreated. NUD patients with reflux-like dyspepsia had significantly more heartburn than the group with essential NUD; otherwise there were no differences between the subgroups of NUD. The individual daily ratings for abdominal pain, heartburn, and global symptoms varied by an average standard deviation of 64%, 97% and 47% of the mean values, respectively, and were independent of treatment or diagnoses. There was an approximately 40% probability that two successive days had different levels of symptoms. Only 10% of the patients showed stable symptoms, and the patients were completely symptom-free for 20% of the observation period. Symptoms in dyspepsia patients disclosed low intensity and high variability in this study. Such factors may be important sources of bias in clinical trials. PMID- 8484081 TI - ADL capacity and loneliness among elderly persons with cognitive impairment. AB - Advancing age brings a natural weakening of functions, making the individual rely more on support from the community and next-of-kin. The purpose of this study was to investigate, in relation to subjective loneliness, the ADL dependence of elderly persons with and without impaired cognitive capacity. 264 persons were interviewed. The Mini-Mental State Examination was used as a screening instrument for obtaining a cognitively-impaired and a normal group of elderly. Persons with impaired cognitive capacity who experienced loneliness had the greatest ADL dependence. PMID- 8484082 TI - Factors associated with consultation length and characteristics of short and long consultations. AB - Consultation length illustrates how general practitioners balance contradictory concerns such as productivity and quality, listening to patients, and handling their own stress. Important factors for consultation length are list size, characteristics of doctors and patients, and character of the problem. The purpose of this study of 463 consultations was to describe factors that are associated with short and long consultations and to examine the relative influence on the consultation length of patients' age and sex, character of the problem, continuity, and the 'doctor's speed'. A questionnaire was used for both doctors and patients. Short consultations were often made by younger male patients about physical problems, while long consultations often were made by older patients about problems with both psychological and physical dimensions. The 'doctor's speed' explained 22.5%, character of the problem 11.6%, and patient's age 2.9% of the variation in consultation length. PMID- 8484083 TI - Prevention of cardiovascular disease within the primary health care system- feasibility of a prevention programme within the Sollentuna primary health care catchment area. AB - OBJECTIVE: To integrate prevention of cardiovascular disease within the primary health care. DESIGN: A prevention programme which combines population and individual high-risk strategy. SETTING: The Primary Health Care in Sollentuna, Stockholm, Sweden. MAIN OUTCOME MEASURE: Characteristics of, and risk factor prevalence among, persons registered in the prevention programme. RESULTS: During the first year more than 2000 persons, representing every tenth visitor and 6% of the population aged 15-60 years, were registered in the prevention programme. 90% were < or = 60 years and 62% were women. A large proportion (70%) had risk factors that required advice, treatment, and follow up. 24% of the men and 27% of the women were smokers, 68% and 62% respectively, had serum cholesterol > or = 5.2 mmol/l, and 33% and 22% had a diastolic blood pressure > or = 90 mmHg. CONCLUSION: The present study implies that it is possible to integrate a large scale prevention programme in the existing primary health care organization. The prevalence of risk factors in those who enter the prevention programme is high, which places great demands for treatment and follow up. PMID- 8484084 TI - Medical audit based on computer-stored patient records exemplified with an audit of hypertension care. AB - OBJECTIVE: To audit hypertension care at a health centre using computer-based patient records as the source of information and a query language as the analysis tool. DESIGN: Retrospective database study comparing hypertension care in 1989 with hypertension care in 1990. SETTING: One health centre in Sweden with six general practitioners and two doctors on vocational training. PARTICIPANTS: All patients with hypertension in 1989 and 1990. MAIN OUTCOME MEASURE: The percentage of records that complied with the criteria in the hypertension care protocol. RESULTS: 585 records in 1989 and 574 records in 1990 were reviewed automatically by a series of 30 database queries. The computer time needed for the review was eight hours. The first audit showed deficiencies in the management of hypertension, in particular concerning patient history taking and risk factor analysis. The second audit, after the introduction of the hypertension care protocol, showed some minor improvements in the recording and also an increased rate of well treated hypertensive patients. CONCLUSION: Computer-based patient records may facilitate the review of medical records that is needed in medical audit. The audit demonstrates the gap between optimal care and clinical reality. PMID- 8484085 TI - Who consults for rape? Sociodemographic characteristics of rape victims attending a medical rape trauma service at the Emergency Hospital in Oslo. AB - OBJECTIVE: To consider the number of victims of rape and attempted rape in a city (Oslo) who sought treatment when medical help had been made available. To examine the sociodemographic characteristics of the patient group that applied for help. DESIGN: Prospective study. SETTING: A rape trauma service (RTS) established at the Emergency Hospital in Oslo. The service is free, open around the clock, and independent of police notification. PARTICIPANTS: All patients attending RTS from 1 January to 31 December. RESULTS: 164 women and four men applied for medical treatment in 1987, four times as many as in 1985, before RTS was started. Their ages varied between 14 and 89 years, with a median of 27 years. Women aged 14-39 years were significantly over-represented in relation to the general female population of Oslo. Married women were significantly under-represented among the female patients, both married women raped by their spouses and married women raped by other men. 45 patients stated that they had been sexually assaulted on a previous occasion without reporting the incident or applying for help. CONCLUSION: Compared with the police an available medical service for rape victims reached four times as many rape victims as in 1985, from a larger share of the population. PMID- 8484086 TI - [The definition and epidemiology of bacterial vaginosis]. AB - Bacterial vaginosis is a condition with a flora change in the vaginal where a lactobacilli-dominated flora is exchanged with an abundant complex flora dominated by strict and facultative anaerobic bacteria. The condition seldom occurs in prepubertal girls and post-menopausal women, suggesting an hormonal component in its etiology. Recurrent episodes of bacterial vaginosis are frequent. Three out of four criteria should be fulfilled for establishing the diagnosis of bacterial vaginosis, i.e., an increased (often homogeneous) vaginal discharge, a positive amine test, the presence of a great number of clue cells, a vaginal pH > or = 4.5. There are no hard data supporting that bacterial vaginosis is a sexually transmitted disease. Cytological changes (CIN I, II, III) have been found more often in women with bacterial vaginosis than in those without this condition. It has been proposed that nitrosamines from the abundant vaginal bacterial flora may be oncogenic, a correlation which, however, needs to be proved. The reservoir for one or more of the bacterial vaginosis-associated organism, e.g., some Bacteroides and Mobiluncus spp., Gardnerella vaginalis and Mycoplasma hominis, is probably the distal intestinal tract and the mouth. Sparse or even a moderate number of clue cells are present in many women who do not have bacterial vaginosis. A vaginal pH of 4.7 seems to be a better cut-off level than 4.5. There is a statistical correlation between bacterial vaginosis and obstetrical complications. PMID- 8484087 TI - [Clinical and colposcopic aspects of bacterial vaginosis]. AB - Bacterial vaginosis is characterized by an uniform, malodorous, white-grey discharge. The presenting symptom is generally the unpleasant smell of the vaginal discharge, particularly following the menses or intercourse. Other functional signs, such as pruritus, dysuria and dyspareunia are rare. Inflammatory signs are frequent, and can be revealed by colposcopy with the Lugol test: this shows punctuate colpitis with small regular points corresponding histologically to an inflammatory focus in the connective tissue. The term "vaginitis" is avoided because of the absence of polymorphonuclear cells in the vaginal discharge, despite the presence of inflammation. Bacterial vaginosis has been held responsible for prematurity, small birthweight and post-partum infection. Nonetheless, Gardnerella vaginalis and Mobiluncus spp can be recovered from the vaginal flora of women with no signs of inflammation. PMID- 8484088 TI - [The bacteriologic diagnosis of bacterial vaginosis in an urban practice]. AB - The term "bacterial vaginosis" carries both bacteriologic and clinical connotations. Indeed, it implies that the vagina is uninflamed (as shown by the absence of polymorphonuclear neutrophils), but that potential pathogens (particularly Gardnerella vaginalis) are present. Many studies conducted over the last 10 years have shown that a tentative diagnosis is simple to make, based on the sniff test, the aspect of the vaginal discharge, the presence of clue cells, and the absence of polymorphonuclear cells and lactobacilli on fresh smears. However, classical treatment with metronidazole can be insufficient given the innumerable microbial associations, and a more thorough bacteriological diagnosis is required. The presence of anaerobes is suggested by a positive sniff test. Direct examination reveals small Gram-negative rods in clue cells, but cannot differentiate between commensal atypical lactobacilli and Gram-positive anaerobes. Culture with CO2 supplementation or in anaerobic conditions yields Bacteroides and Mobiluncus spp, frequently associated with Gardnerella vaginalis and pathogenic Fusobacterium spp. Culture in appropriate conditions will detect metronidazole-resistant Propionibacteria and pathogenic anaerobic cocci. Antibiotic susceptibility testing of these organisms is costly and time consuming, but can avoid therapeutic failures. Gardnerella vaginalis is also frequently associated in bacterial vaginosis with endogenous (mainly E. coli and group B streptococci) and Ureaplasma. Antibiotic susceptibility testing is useful if the predominant members of the flora are Gram-negative aerobes, group D streptococci or pathogenic anaerobes. Bacterial vaginosis is simple to diagnose but poses a real therapeutic problem since some cases call for a simple readjustment of the commensal flora while others require full chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484089 TI - [Recent bacteriologic data: from physiopathology to treatment]. AB - Bacterial vaginosis is characterized by a change in the vaginal ecosystem in which Lactobacillus spp, the dominant members of the normal flora, are replaced by an association of various bacterial species including Gardnerella vaginalis, anaerobes (Bacteroides spp, Prevotella spp, Porphyromonas spp, Peptostreptococcus spp and Mobiluncus spp) and Mycoplasma hominis. The reasons for this imbalance are unknown, although the loss of lactobacilli that produce hydrogen peroxide (which is toxic for G. vaginalis and numerous anaerobes) may be an essential element. The introduction of one or several of these species into the vagina (they can occasionally be isolated in small numbers even in the absence of vaginosis) following intercourse or from the intestinal tract may also play a role. G. vaginalis itself is not considered to cause vaginosis, but is almost always present and multiplies rapidly; in addition, it has a high capacity for adherence to epithelial cells both in vivo and in vitro. It is now agreed that the concomitant growth of one or several anaerobic species is required for bacterial vaginosis to develop. Our knowledge of the bacteriology of bacterial vaginosis has implications for diagnosis and treatment. It is now possible to obtain a precise bacteriologic diagnosis, not by culturing G. vaginalis (a costly and low-yield procedure), but by direct examination of the vaginal flora after Gram staining, which shows the replacement of lactobacilli by a characteristic polymorphic flora. Therapy is based on the use of antibiotics such as the imidazoles, which are active against G. vaginalis and anaerobes, but not against the commensal lactobacilli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484090 TI - [Bacterial vaginosis: what risks for the mother and child?]. AB - Bacterial vaginosis are characterized by a polymicrobial proliferation of anaerobic organisms and the disappearance of the commensal lactobacilli, which can cause ascending utero-adnexitis and endanger ongoing pregnancy. The role of anaerobes in utero-adnexitis and tubal abscess was first raised in 1973 par Eschenbach. Several authors have since established correlations between bacterial vaginosis and both pain from the uterine appendages and gynecologic infections, particularly post-abortum. Bacterial vaginosis is a major problem in pregnant women, given its high prevalence (15-20 p. cent) and significant relationship with premature delivery and premature rupture of the membranes (at less than 37 weeks of amenorrhea) in epidemiological case-control and cohort studies taking into account demographic and concomitant obstetric characteristics. In particular, histological lesions indicative of chorioamniotitis have been correlated with prematurity and with the presence of bacteria (usually those involved in vaginosis) in the amniochorial space. Bacterial vaginosis can give rise to ascending infections which reach the amniochorial space and cause uterine contractions or alter the amniochorial membrane, leading to premature rupture of the membranes. These epidemiological data must, however, be confirmed by controlled trials of antibiotics active in bacterial vaginosis and their preventive effect on prematurity and premature rupture of the membranes. Finally, bacterial vaginosis can play a role in endometritis following both natural and caesarean delivery; this has been shown in multivariate analyses with adjustment for maternal age, duration of labor and rupture of the membranes, and isolation of bacteria associated with bacterial vaginosis from the endometrium. PMID- 8484091 TI - [Antibiotics and bacterial vaginosis]. AB - The two questions that arise in the treatment of bacterial vaginosis are: who should be treated and how can the frequent recurrences be avoided? Metronidazole is the reference agent in this setting. At a dose of 500 mg bid for 3-7 days, the clinical and bacteriologic cure rates range from 80 to 100 p. cent. Clindamycin and amoxycillin-clavulanic acid are both effective; amoxycillin is less effective but can be used when other antibiotics are contraindicated (pregnancy, etc.). Not all cases of bacterial vaginosis should be treated, as about 50 p. cent are totally asymptomatic. However, the risk of occasionally serious infectious complications calls for treatment of patients with risk factors, such as symptomatic vaginosis, high-risk pregnancy, a history of gynecological infection, pelvic surgery (particularly by the vaginal route), and sterility. Although bacterial vaginosis is not strictly a sexually transmitted disease, treatment of the partner can reduce the risk of recurrence. Suitable antibiotic treatment is usually associated with clinical and bacteriological resolution of bacterial vaginosis. Unfortunately, long-term follow-up of these patients has shown a risk of recurrence as high as 80 p. cent at nine months, for reasons which remain to be elucidated. PMID- 8484092 TI - Reduction of tumor necrosis factor alpha and interleukin-1 beta levels in human synovial tissue by interleukin-4 and glucocorticoid. AB - The effects of recombinant human interleukin-4 (IL-4) and the glucocorticoid, dexamethasone, on tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) levels in cultures of rheumatoid and osteoarthritic synovial tissue were studied. Low concentrations of IL-4 and dexamethasone suppressed the levels of both cytokines in the supernatants of both types of tissue after stimulation with lipopolysaccharide (LPS); the IL-1 beta and TNF alpha levels were measured by ELISA. It is suggested that it is the monocyte/macrophage in the synovial tissues that is responsive to the inhibitors. It is proposed that glucocorticoids may act on synovial tissue in this manner in vivo and IL-4 may do so if administered intraarticularly. PMID- 8484093 TI - T-cell receptor V beta chain expression in patients with juvenile rheumatoid arthritis. AB - The V beta chain repertoire in peripheral blood T-cell was analyzed in 23 patients with juvenile rheumatoid arthritis (JRA). Of these, 15 patients had active disease as defined by tender and swollen joints. The ESR was elevated in all but three patients, C-reactive protein (CRP) was elevated in eight. Three patients were investigated during active and inactive phases of the disease. In the active phase of the disease T-cell composition was characterized by an increased number of CD4+ helper cells due to a marked increase in the CD4+CD45RA+ subgroup (34.0 +/- 10.9%, P < 0.001) and a decrease in CD8+CD29+ T-cells (10.3 +/ 5.6%, P < 0.05) compared to controls (15.4 +/- 10.0% and 17.8 +/- 12.3%, respectively). Using the monoclonal antibodies available to determine T-cell receptor (TCR) expression, patients with active disease demonstrated a significant predominance of T-cells bearing TCRs of the V beta 5 family as determined by flow cytometry (7.6 +/- 6.7 vs 3.4 +/- 1.3 in controls, P = 0.01). In active polyarthritis, up to 24% of peripheral blood T-cells expressed TCRs of the same family. In the majority of JRA patients and especially in non-active disease, no preferential TCRs were found compared to controls. However, even defining only a part of TCRs by immunofluorescence, in certain patients a preferential or dominant expression of a single V beta gene family in the T-cells was found, supporting the concept of an involvement of T-cells in the autoimmune pathogenesis of JRA. PMID- 8484094 TI - Repeated detection of Borrelia burgdorferi DNA in synovial fluid of a child with Lyme arthritis. AB - In the pathogenesis of late Lyme borreliosis the relative importance of the causative organism, Borrelia burgdorferi, and the immune response of the host, including autoimmune phenomena, is not yet known. We describe a 7-year-old boy with Lyme arthritis from whom two synovial fluid samples were obtained 5 months apart and up to 17 months after the first appearance of arthritis. Both synovial fluid specimens were shown to contain borrelial DNA by nested polymerase chain reaction for the amplification of portions of the genes for flagellin and OspA. Thus, Borrelia burgdorferi may persist within the joint even during late stages of the disease. PMID- 8484095 TI - Serological profile of rheumatoid arthritis in west Africa. AB - Rheumatoid arthritis (RA) in West Africa is atypical in a number of respects. In order to investigate this we evaluated the serological profile of a series of West African patients diagnosed as having RA. We found the presence of a wide range of autoantibodies including antinuclear antibodies (ANA), anticardiolipin antibodies and antineutrophil cytoplasmic antibodies but the pattern of these autoantibodies was similar to that reported in other studies. Our serological studies support the hypothesis that these patients do have RA and the presence of these autoantibodies is of interest with regards to implications for diagnosis. PMID- 8484096 TI - Does sport negatively influence joint scores in patients with juvenile rheumatoid arthritis. An 8-year prospective study. AB - The influence of sporting activities performed using joint protective measures on deterioration in hand and lower extremity function was evaluated over 8 years in 62 patients with juvenile rheumatoid arthritis (JRA). Sporting activities usually recommended to patients with JRA, such as cycling and swimming, did not negatively influence hand or lower extremity function as compared to a control group of patients not taking part in sporting activities. Besides cycling and swimming, other sporting activities were only performed by a minority of patients (less than 10%). Decreases in total joint scores of both the hands and lower extremities, showed significant correlations with disease duration in patients taking part and in patients not taking part in sporting activities. Polyarticular onset of disease was associated with higher total joint scores of the hands as compared to pauciarticular onset of disease. In lower extremity function, no difference was found between patients with polyarticular onset and patients with pauciarticular onset. Disease duration of longer than 10 years, accompanied by severe functional deterioration, was followed by low participation in sporting activities. Therefore, we suggest that appropriate sporting activities, such as cycling and swimming, can be advised to patients with JRA regardless of disease duration, since no negative effects were observed in our study over a period of 8 years. PMID- 8484097 TI - Chromosome abnormalities in peripheral lymphocytes from patients with progressive systemic sclerosis. AB - Chromosomal abnormalities in cultured peripheral lymphocytes from 14 progressive systemic sclerosis (PSS) patients and 15 normal subjects were examined. No increase was observed in the frequency of chromosome aberrations in PSS patients who had not received any medical treatment. Those who had received medication showed an increased frequency of dicentrics (0.3%) although the frequency was not significantly higher than that for normal subjects. It is not clear, however, whether the increase was due to the hypersensitivity of PSS patients to agents used for therapeutic purposes. PMID- 8484098 TI - Nodules of the shoulder girdle in two Indonesian villages. AB - During a community survey of rheumatic complaints in a Javanese rural population, fibrous shoulder girdle nodules having a consistent form and position were observed in seven men. This was 2.3% of 303 men with complaints examined from a total population of 2184 men surveyed by house-to-house interviews (response rate 95.2%). Nodules were not seen in any of the 640 women examined with complaints from a total population of 2499, nor were they seen in 130 men and 159 women with complaints from an urban population of 481 men and 590 women over the age of 15 years. It was considered most likely that these shoulder nodules were the result of longstanding repetitive mechanical irritation due to carrying heavy loads by a resilient wooden pole balanced across the shoulder. PMID- 8484099 TI - Multicentric Castleman's disease in a patient with primary Sjogren's syndrome. AB - A 38-year-old woman suffering from primary Sjogren's syndrome for 2 years developed angiofollicular hyperplasia (multicentric Castleman's disease). In Sjogren's syndrome (SS) a number of findings indicate the presence of a B-cell hyperactivity that may evolve to a lymphoproliferative disorder. This report adds another pathological event to the complex spectrum of lymphoproliferative diseases in SS. PMID- 8484100 TI - Excessive fibrosis of supraclavicular lymph-node granulomas in a patient with progressive systemic sclerosis. AB - The case of a 29-year-old white female with a 7-year history of typical scleroderma is presented who developed excessive fibrosis of the supraclavicular lymph nodes. After 3 years of disease, firm right supraclavicular lymphadenopathy appeared, accompanied by a high fever. Biopsy revealed non-caseating granulomas and short-term antituberculous therapy was ineffective. The symptoms finally responded to steroids, but adenopathy persisted. A second biopsy, 40 days after the first, disclosed a similar picture with some degree of fibrosis of the granulomas. Four years later, with stony hard right supraclavicular adenopathy persisting, a third biopsy showed excessive fibrosis of the granulomas within the node and destruction of its architecture. It is postulated that the primary disease of this patient might be responsible for this clinical picture. The present seems to be the first report of such a case in the literature. PMID- 8484101 TI - Evidence for an ongoing role of class I histocompatibility molecules for the production of interleukin-2 in response to suboptimal concentrations of phytohaemagglutinin. AB - To examine the role of cellular interactions involving class I histocompatibility antigens in the response to low concentrations of phytohaemagglutinin, we studied the effect of antibodies to components of these antigens on proliferative responses, interleukin-1 and interleukin-2 production, and IL-2 receptor expression. Antibody to human beta 2-microglobulin (beta 2m) had an inhibitory effect both on IL-2 accumulation at 48 h of culture and on the proliferative response 24 h later. Exogenous IL-2 completely reconstituted the inhibited proliferative responses, and also restored the modest decrease in IL-2 receptor expression that was induced by anti-beta 2m. Pretreatment of either purified monocytes or T cells with anti-beta 2m had a similar inhibitory effect both on proliferation and on interleukin-2 production. By contrast, IL-1 production by LPS- or silica-stimulated monocytes was not affected by this antibody. Kinetic experiments demonstrated that anti-beta 2m was equally inhibitory when added at the initiation of culture or after 24h, and significant inhibition occurred when the antibody was added as late as 48 h. Our results are consistent with an ongoing role for class I antigens in the cellular interactions between lymphocytes and accessory cells required for the production of IL-2. PMID- 8484102 TI - Organ-specific regulation of interferon-gamma, interleukin-2 and interleukin-2 receptor during murine infection with Trypanosoma cruzi. AB - We have studied the expression of IFN-gamma, IL-2 and IL-2 receptor (IL-2R) at the mRNA and protein levels in spleen and lymph node cells from Trypanosoma cruzi infected BALB/c mice. At 21 days post infection (dpi) (peak of parasitaemia), spleen cells stimulated with Con A for 16 h showed a reduced IFN-gamma, IL-2 and IL-2R mRNA production compared with non-infected controls. Lymph node cells obtained at 4, 21 or 60 dpi produced similar amounts of IFN-gamma, IL-2 or IL-2R transcripts after mitogen stimulation as uninfected controls. Spleen cells obtained at 21 dpi showed a lower Con A proliferative response and IL-2R expression compared with non-infected controls, while the proliferation and IL-2R expression of lymph node cells at 21 dpi was unaltered. Supernatants from 48 h Con A-stimulated spleen and lymph node cells from mice at 21 dpi had very low levels of IL-2 but contained significantly higher levels of IFN-gamma compared with the supernatants of cells from non-infected mice. The latter phenomenon correlates with an accelerated rate of IFN-gamma mRNA accumulation. PMID- 8484103 TI - Protective opsonic activity of antibodies against fibronectin-binding proteins (FnBPs) of Staphylococcus aureus. AB - In this report, opsonic activity of hyperimmune rabbit IgG against fibronectin binding proteins (gal-FnBP A and ZZ-FnBP B) of Staphylococcus aureus is described. Moreover, the action of IgG purified from serum of rabbits immunized with 'combined vaccine' (fibronectin-binding protein A+collagen-binding protein+alpha-toxoid) is shown. The opsonic activity has been studied in an in vitro phagocytosis assay as well as in vivo. Mice which had been infected intraperitoneally with S. aureus strain Cowan 1 pretreated (opsonized in vitro) with specific anti-FnBPs IgG were able to eliminate the staphylococci from the peritoneal cavity and liver more rapidly than controls. Also, clearance from the bloodstream of intravenously injected S. aureus Cowan 1 as well as S. aureus U320, opsonized with IgG anti-FnBPs or anti-FnBP+CnBP+alpha-toxoid, was more effective than observed in control groups. In other in vivo experiments it was shown that mice passively immunized with hyperimmune IgG anti-FnBP (one or two doses, intravenously) before challenge with S. aureus Cowan I eliminated the bacteria better than controls injected only with preimmune IgG. PMID- 8484104 TI - Cyclosporin A does not inhibit IL-1 alpha-induced epithelial cell IL-6 secretion. AB - Trauma and infection activated a murine mucosal IL-6 response in different ways: the IL-6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL-6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA-insensitive IL-6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor alpha (TNF-alpha). The E. coli strain had been used for the in vivo experiments which led to this study, and IL-1 alpha and TNF-alpha were likely to be released during infections and trauma. The secretion of IL-6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL-1 alpha and TNF-alpha stimulated an IL-6 response in the two epithelial cell lines. The IL-1 alpha-induced IL-6 response was rapid, and the secreted IL-6 levels were significantly higher than those induced by E. coli Hu734 or TNF-alpha. The IL-6 response to IL-1 alpha was insensitive to CsA. By contrast, the IL-6 response to E. coli Hu734 and TNF-alpha was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL-6 response. IL-1 alpha may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion. PMID- 8484105 TI - Aggregated human immunoglobulins bind to modified proteins. AB - Human immunoglobulins treated at 55 degrees C in vitro are able to interact with maleylated bovine serum albumin (mBSA), but not with unmodified BSA. Gel filtration experiments demonstrated that the mBSA binding is associated with a high molecular weight complex of aggregated IgG. This aggregated IgG with binding capacity for mBSA could also be generated in vitro by treatment of human IgG at 37 degrees C or 40 degrees C and by incubation with human neutrophils. Furthermore, IgG aggregates with binding activity for mBSA could be detected in untreated synovial fluids from rheumatoid arthritis patients, indicating that these complexes occur in vivo. The phenomenon of binding to aggregated IgG was extended to other modified proteins such as maleylated human serum albumin (mHSA), acetyl low density lipoprotein (Ac-LDL) and BSA reacted with oxidized linolenic acid. Soluble forms of these modified proteins were able to compete for the interaction between aggregated IgG and surface-bound mBSA. We also found that aggregated IgG enhanced the Ac-LDL-dependent foam cell formation. These findings suggest a role for aggregated IgG in the metabolism of oxidized proteins. PMID- 8484106 TI - Oligoclonal development of germinal centre cells as detected by anti-idiotype antibodies. AB - Experimental models using immunization with known haptens have shown that germinal centres develop from only a limited number of precursor cells which expand in an oligoclonal fashion. Using a panel of antibodies raised against the idiotype of follicle centre cell lymphomas and known to be reactive only with a few normal B cells, we could demonstrate that individual clones can be identified within germinal centres of individual follicles of human lymph nodes and tonsils. Therefore also in humans in a non-experimental, natural situation, germinal centres expand in an oligoclonal fashion. PMID- 8484107 TI - Evaluation of nutritional status in persons with spinal cord injury: a prerequisite for successful rehabilitation. AB - Evaluation of nutritional status is a pre-requisite for planning a comprehensive and appropriate nutritional care plan for spinal cord injured (SCI) patients. A nutritional assessment reveals the nutritional status of a patient and identifies the objectives of nutritional care. There is no single measurement that totally reflects the state of a patient's nutritional health. Besides anthropometric, laboratory, and dietary intake, a patient's social and medical history are needed to develop an individualized plan. The outcome of establishing a screening and assessment program results in quality and cost-effective nutritional care for patients. Providing optimal nutritional care at the onset of SCI can help reduce complications, decrease length of hospital stay, and enhance the rehabilitation outcome. PMID- 8484108 TI - Methylprednisolone after spinal cord injury. AB - The assumption that maximal spinal cord injury occurs at the moment of trauma is being challenged by emerging evidence that cellular injury continues after the acute event. Efforts are now being made to alter the course of secondary injury in order to improve the functional outcome of survivors. Methylprednisolone has been studied in two clinical trials--the National Acute Spinal Cord Injury Studies (NASCIS I, NASCIS II)--to determine its ability to protect compromised but viable cellular elements, and thus improve outcome. The purpose of this paper is threefold: (1) to explore the putative mechanisms of secondary spinal cord injury, (2) to examine the role of methylprednisolone in spinal cord injury, and (3) to discuss the findings and clinical implications of NASCIS I and NASCIS II. PMID- 8484109 TI - Carbon monoxide and dilation of blood vessels. PMID- 8484110 TI - UCSF Research Institute: no Hughes approval. PMID- 8484111 TI - Big science enters the clinic. PMID- 8484112 TI - Affirmative action for clinical trials. PMID- 8484113 TI - Proposal to counter scientist 'shortage' draws fire. PMID- 8484114 TI - New test catches drug-resistant TB in the spotlight. PMID- 8484115 TI - New colon cancer gene discovered. PMID- 8484116 TI - Zagury probe concluded. PMID- 8484117 TI - The many roads that lead to Ras. PMID- 8484118 TI - The nitrogenase FeMo-cofactor and P-cluster pair: 2.2 A resolution structures. AB - Structures recently proposed for the FeMo-cofactor and P-cluster pair of the nitrogenase molybdenum-iron (MoFe)-protein from Azotobacter vinelandii have been crystallographically verified at 2.2 angstrom resolution. Significantly, no hexacoordinate sulfur atoms are observed in either type of metal center. Consequently, the six bridged iron atoms in the FeMo-cofactor are trigonally coordinated by nonprotein ligands, although there may be some iron-iron bonding interactions that could provide a fourth coordination interaction for these sites. Two of the cluster sulfurs in the P-cluster pair are very close together (approximately 2.1 angstroms), indicating that they form a disulfide bond. These findings indicate that a cavity exists in the interior of the FeMo-cofactor that could be involved in substrate binding and suggest that redox reactions at the P cluster pair may be linked to transitions of two cluster-bound sulfurs between disulfide and sulfide oxidation states. PMID- 8484119 TI - Sequences and structures required for recombination between virus-associated RNAs. AB - RNA recombination has been described for a number of viruses in the plant and animal kingdoms, but the mechanisms of selection of recombination sites are poorly understood. The nonrandom recombination between two subviral RNAs associated with turnip crinkle virus was used to study the requirement for specific sequences and structures in the generation of recombinant molecules. Single-base mutations that disrupted either the stem or the loop of one of the two computer-predicted stem-loop structures eliminated detectable recombinant molecules. However, recombinants were detected if compensatory mutations were generated that re-formed a stable hairpin structure. These results provide evidence for the necessity of specific structures in the formation of recombinant molecules in this system. PMID- 8484120 TI - Genetic mapping of a locus predisposing to human colorectal cancer. AB - Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease. PMID- 8484121 TI - Clues to the pathogenesis of familial colorectal cancer. AB - A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of "familial" cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes. PMID- 8484122 TI - Microsatellite instability in cancer of the proximal colon. AB - Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q. Differences between tumor and normal DNA were detected in 25 of the 90 (28 percent) tumors examined. This instability appeared as either a substantial change in repeat length (often heterogeneous in nature) or a minor change (typically two base pairs). Microsatellite instability was significantly correlated with the tumor's location in the proximal colon (P = 0.003), with increased patient survival (P = 0.02), and, inversely, with loss of heterozygosity for chromosomes 5q, 17p, and 18q. These data suggest that some colorectal cancers may arise through a mechanism that does not necessarily involve loss of heterozygosity. PMID- 8484123 TI - Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages. AB - Effective chemotherapy of tuberculosis requires rapid assessment of drug sensitivity because of the emergence of multidrug-resistant Mycobacterium tuberculosis. Drug susceptibility was assessed by a simple method based on the efficient production of photons by viable mycobacteria infected with specific reporter phages expressing the firefly luciferase gene. Light production was dependent on phage infection, expression of the luciferase gene, and the level of cellular adenosine triphosphate. Signals could be detected within minutes after infection of virulent M. tuberculosis with reporter phages. Culture of conventional strains with antituberculosis drugs, including isoniazid or rifampicin, resulted in extinction of light production. In contrast, light signals after luciferase reporter phage infection of drug-resistant strains continued to be produced. Luciferase reporter phages may help to reduce the time required for establishing antibiotic sensitivity of M. tuberculosis strains from weeks to days and to accelerate screening for new antituberculosis drugs. PMID- 8484124 TI - Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation. AB - The hematopoietically expressed product of the vav proto-oncogene, Vav, shared homology with guanine nucleotide releasing factors (GRFs) [also called guanosine diphosphate-dissociation stimulators (GDSs)] that activate Ras-related small guanosine triphosphate (GTP)-binding proteins. Human T cell lysates or Vav immunoprecipitates possessed GRF activity that increased after T cell antigen receptor (TCR)-CD3 triggering; an in vitro-translated Vav fragment that contained the putative GRF domain was also active. Vav-associated GRF stimulation after TCR CD3 ligation paralleled its tyrosine phosphorylation; both were blocked by a protein tyrosine kinase (PTK) inhibitor. Vav also was a substrate for the p56lck PTK. Thus, Vav is a PTK-regulated GRF that may be important in TCR-CD3-initiated signal transduction through the activation of Ras. PMID- 8484126 TI - New study of nurse vs. physician care shows nurses offer same or better treatment at lower costs. PMID- 8484125 TI - Health care reform. Message from SDNA president. PMID- 8484127 TI - Rural health nursing perspective. Interview by Sara Becker and Kathleen Muir Molton. PMID- 8484128 TI - LPN task force recommends expanding role in i.v. therapy. PMID- 8484129 TI - Sternocostoclavicular hyperostosis. AB - Sternocostoclavicular hyperostosis is a chronic arthro-osteitis affecting mostly juxtasternal structures. It is characterized clinically by painful swelling of the upper anterior chest wall and occasionally is associated with pustulosis palmaris and plantaris. Pathologically there is osteitis, periostitis, and new bone formation of periarticular structures. Two patients are described, and the clinical, laboratory, and radiological findings of 251 reported cases in the English literature are reviewed. PMID- 8484130 TI - Candida arthritis in adult patients who are not intravenous drug addicts: report of three cases and review of the literature. AB - Candida species are an uncommon cause of infectious arthritis, although the frequency has increased during recent years. Three cases of septic arthritis caused by Candida species are reported, and the literature is reviewed. The first patient developed a popliteal cyst infected by Candida albicans after multiple intravenous antibiotic treatments. The second patient had acute myelogenous leukemia and experienced knee arthritis after chemotherapy, and the third suffered oligoarthritis after a second heart transplantation. All patients received treatment with a standard dose of intravenous amphotericin B. Responses were achieved only in the first two cases; the third patient died despite therapy. Thirty-six previously reported Candida arthritis cases are reviewed, and epidemiologic, diagnostic, therapeutic, and prognostic features are analyzed. Cases are divided into two categories: direct inoculation of fungus and hematogenously disseminated disease; these two categories are compared in terms of sex, age, pathogen species, treatment, and survival. Arthritis induced through direct inoculation of fungus is seen in older individuals, is more frequently produced by species other than C albicans (Candida parapsilosis especially), and has a better prognosis than arthritis caused by disseminated candidiasis. Arthritis can be resolved even in the persistence of the systemic disease. It is believed that the first case of Baker's cyst infected by C albicans and the first case of Candida arthritis in a heart transplant patient are reported here. PMID- 8484131 TI - Psychopathology associated with systemic lupus erythematosus: a methodological review. AB - Psychiatric dysfunction is believed to be a common manifestation of systemic lupus erythematosus (SLE). In fact, psychosis is 1 of 11 criteria the American Rheumatism Association used to provide a classification scheme for the disease. Nonpsychotic symptomatology also is frequently attributed to SLE disease pathophysiology. This article is a methodological review of the literature relating to the prevalence of psychiatric dysfunction and whether these problems can be attributed to disease activity. Given the serious methodological limitations in the available literature, definitive point prevalence or lifetime prevalence estimates for psychopathology in patients with SLE are not available. In addition, there is no conclusive evidence that the disease causes nonpsychotic psychiatric dysfunction in these patients. PMID- 8484132 TI - Hypogammaglobulinemia and rheumatic disease. AB - Primary hypogammaglobulinemia describes a heterogeneous group of immunoglobulin disorders mainly composed of X-linked agammaglobulinemia, common variable immunodeficiency, and selective immunoglobulin (Ig) A deficiency. The most serious problems are related to recurrent infections with high-grade encapsulated bacteria. However, a wide variety of rheumatologic disorders also occur in association with hypogammaglobulinemic states. Septic arthritis with usual bacterial pathogens such as Staphylococcus aureus, and unusual bacteria such as Mycoplasma and Ureaplasma species, have been described in these patients. An aseptic nonerosive polyarticular arthritis that resembles rheumatoid arthritis is seen in 10% to 30% of hypogammaglobulinemic patients. Autoimmune disorders such as immune thrombocytopenic purpura, immune hemolytic anemia, juvenile rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, Sjogren's syndrome, essential mixed cryoglobulinemia, chronic active hepatitis, and sarcoidosis have been reported in hypogammaglobulinemic patients. Finally, to complicate matters, many disease-modifying antirheumatic drugs, including gold, D-penicillamine, sulfasalazine, azathioprine, and cyclophosphamide, cause symptomatic hypogammaglobulinemia in some patients. PMID- 8484133 TI - Autoantibody studies in juvenile rheumatoid arthritis. AB - Early studies showed few immunologic abnormalities in juvenile rheumatoid arthritis (JRA) patients. There were no specific laboratory markers useful for diagnosis and assessment of the course of disease in JRA. Previous work showed an association of antinuclear antibodies (ANA) with early-onset pauciarticular disease and iridocyclitis. Similarly, the presence of 19S immunoglobulin (Ig) M rheumatoid factors (RF) was associated with late-onset polyarticular disease in girls. More recent studies have detected many unique autoantibodies. Newer assays show 19S IgM RF in up to 35% of JRA patients, although still mainly in girls with late-onset polyarticular disease. Hidden 19S IgM RF can be shown in up to 75% of JRA patients using different procedures, primarily in those with active polyarticular-or pauciarticular-onset disease. Immune complexes have been detected in JRA patients by means of different techniques; their presence usually correlates with active disease. Studies on a specific ANA in JRA have shown no common extractable nuclear antigen, but antihistone antibodies have been found in up to 75% of cases, again mainly in those with pauciarticular onset and iritis. Finally, a variety of unusual immunologic proteins have also been detected, including anti-ocular, anti-cellular, anti-cardiolipin, anti-perinuclear factor, and anti-collagen antibodies. This review evaluates the significance of these antibodies that can now be found in JRA. PMID- 8484134 TI - Rheumatologic disease among Air Force recruits: a multimillion-dollar epidemic. AB - A retrospective analysis of medical discharge diagnoses of Airmen Basic undergoing basic military training in the Air Force for a 1-year period from 1990 to 1991 was performed. The weighted variable cost to replace each recruit discharged was then used to estimate the cost to the Air Force attributable to rheumatologic disease. Musculoskeletal disorders were found to account for 67% of medical discharges, costing the Air Force at least 2.70 million dollars during the period under study. The patellofemoral syndrome, pes planus deformity, and low back pain were the most frequently encountered diagnoses. PMID- 8484135 TI - Diabetic muscular infarction. AB - In the evaluation of patients with a painful atraumatic mass in an extremity, the clinician should consider a number of clinical entities: primary tumor of muscle, focal or localized nodular myositis, local muscular abscess or soft-tissue infection, osteomyelitis, and thrombophlebitis. A rare complication of diabetes, viz, diabetic muscular infarction, heretofore not reported in the rheumatic disease literature is reviewed. This entity is compared with the conditions of focal and localized nodular myositis, which are nearly as rare. PMID- 8484136 TI - [Opportunistic infections in patients with disordered immune status]. AB - Dysfunction of the immune system can result in opportunistic infections, which are frequently responsible for high morbidity and mortality. With regard to surgery, opportunistic infections are found in specific risk groups, including individuals with tumors, AIDS, thermic or mechanical trauma and organ transplantation. These infections can be caused by bacteria, fungi, viruses and protozoa. If there are indications of a possible opportunistic infection, a rapid diagnosis is required, followed by immediate therapeutic intervention. PMID- 8484137 TI - [Necrotizing soft tissue infections]. AB - Necrotizing soft tissue infections are a group of life- and limb-threatening infections. They are caused by aerobic and anaerobic bacteria occasionally in a synergistic polymicrobial combination. The literature describing necrotizing soft tissue infections is controversial and often contradictory. Depending on their clinical appearance, tissue level and microbiological findings, necrotizing soft tissue infections are classified into two major groups, infections within the subcutaneous/fascia niveau and within the muscle level. Necrotizing infections of the subcutaneous level are further differentiated in hemolytic streptococcal gangrene, necrotizing fasciitis, clostridium fasciitis, and anaerobic nonclostridium fasciitis. In particular, necrotizing fasciitis is a rapidly progressing process, which is characterized by suppurative fasciitis, following by vascular thrombosis and cutaneous gangrene and is often accompanied by severe systemic toxicity, seen as septic-toxic shock and progressive (multi-) organ failure. Nineteen cases of necrotizing soft tissue infections were treated at the Department of Surgery, University Hospital of Zurich, between 1989 and 1992. These infections originated from "neglected trauma" in 9 (9/19), drug injections in 4 (4/19), acute infections in 3 (3/19), operative wounds in 2 (2/19) and perforation of the intestine in 1 case (1/19). Most of the patients (13/19) suffered from chronic debilitating diseases and were compromised by a suppressed immune system. We treated two groups of patients, one with septic-toxic clinical course and the other without. Eleven patients (11/19) belonged to group one and four of them, showing necrotizing fasciitis of the trunk, died as a result of multiorgan failure (MOF). Furthermore, three patients in this group had a limb amputated. In the other group without septic-toxic signs, no one died or lost a limb. The two groups differed also in length of hospital stay, an average of 60 days in group one (23 days intensive care) and 25 days in group two. Our results suggest that prompt recognition and treatment of necrotizing soft tissue infections are essential for the patient's survival. Often the full extent of the infections is underestimated initially, resulting in delayed surgical therapy. To control the rapidly spreading necrosis, early diagnosis and radical debridement of the affected tissue are essential and should be done without compromise, even if the affected limb must be amputated. PMID- 8484138 TI - [Tuberculosis of bones and joints]. AB - In developing countries tuberculosis of the bones and joints is a disease with an endemic character. In industrialized nations it is also gaining importance again as a result of social problems and of cases of immune deficiency. After the bacteriologic/histologic diagnosis of tuberculosis of the bones and joints, the primary therapy is non-operative with immobilization and antituberculous chemotherapy. Nevertheless, there are indications when an abscess and arthrodesis or spondylodesis must be cleaned operatively. An absolute and urgent indication for operative cleansing and stabilization is acute progressive paraplegia. PMID- 8484139 TI - [Immunologic monitoring after severe trauma]. AB - Trauma, burn injury, and major surgery lead to severe suppression of the immune system with an increased susceptibility to septic complications. Therefore, the monitoring of essential immune functions in the early and late post-traumatic course may permit trauma patients with an increased risk for infectious complications to be identified. Most functions of the specific and non-specific immune system can be determined with ELISA, RIA, or other immunological techniques. However, only a small number of these techniques demonstrate an acceptable sensitivity and specificity for infectious complications. Moreover, the techniques used in daily monitoring should be simple, reproducible and not expensive with regard to materials. For immunological monitoring we suggest two scoring systems (ISS; APACHE II), biochemical parameters (elastase, neopterin, CRP, lactate), and interleukin-6 plasma levels. The clinical relevance of this monitoring must be proven in clinical studies. PMID- 8484140 TI - [A new procedure for removal of foreign bodies in the area of the head]. AB - Identification and extraction of penetrating cranial foreign bodies can cause problems in some cases. Small fragments localized deep in the orbit or cerebrum can be especially hard to detect. Severe bleeding and traumatized anatomy can make orientation difficult. We used a new localizing device, computer-assisted surgery (CAS), to good effect in six such cases. CAS is a localizing technique designed to assist the head surgeon during surgery, providing real-time position information. The method is based upon a three-dimensional volume model of the patient's skull generated by preceding computed tomography imaging procedures (CT or MRI). Intraoperative correlation of a 3D-model and the patient's skull allows for real-time position display of a surgical instrument on the monitor screen. Thereby the surgeon is able to localize even small foreign bodies without extensive exploration. In the case of multiple foreign bodies the surgeon calls up a simple documentation facility recording which of the visible fragments have already been extracted. We successfully used the system for extraction of orbital foreign bodies in four and intracerebral foreign bodies in two cases. In a 4-year old child with gunshot injury the bullet was located in the precentral region and was easily extracted with the CAS system. In a 21-year-old man 39 glass fragments were extracted from the left orbit. In a 36-year-old man a bone fragment was dislocated to the apex of the orbit directly under the optic nerve. Location and extraction were achieved without damage to the orbital structures with the help of the CAS system. PMID- 8484141 TI - [Management of unstable forearm shaft fractures in children]. AB - Complete dislocation fractures of the forearm are rare in children. Operative treatment is indicated if it is an open fracture and if neurovascular injury is present. There is no accepted standard treatment--operative or nonoperative--for fractures that cannot be accurately reduced and stabilized. In the last 10 years we have operated on 37 fractures of the forearm in children. In 22 cases the indication for operative treatment was that the fractures could either not be reduced or could not be stabilized. Our results show that most fractures were not recognized as unstable (17 out of 22 cases), and therefore several reduction maneuvers (2 to 4 times) were performed before definitive stabilization was obtained via an operation. It is therefore mandatory that unstable fractures of both bones or of one bone be operated on whereas semistable fractures (one bone completely fractured) should be reduced under general anesthesia and operative standby. For the surgical treatment of unstable forearm fractures we recommend intramedullary fixation by dynamic nailing or plate osteosynthesis in younger patients (5-10 years) and open reduction and plate osteosynthesis in older patients and in open fractures or fractures with primary neurovascular impairment. PMID- 8484142 TI - Adolescent idiopathic scoliosis--early menarche, normal growth. AB - Growth has long been known to be relevant to the development and prognosis of spinal deformity and abnormalities have been considered in the etiology of idiopathic scoliosis. Age at menarche, as an indicator of puberty, in 303 girls with idiopathic scoliosis 10 degrees or more from the Dublin school screening program was 13.13 years, 0.39 years earlier than the national mean for Irish girls. This difference is statistically significant (P < 0.01). The heights of 214 of these girls aged 10-15.5 years at diagnosis and at least 14 years at follow-up, after a minimum 6 months, were compared with the national standards. It was found that, although those diagnosed at a younger age were generally taller than their peers, this was not true for those diagnosed at a later age or for anyone at final follow-up. This points to an early pubertal growth spurt in girls with adolescent idiopathic scoliosis but not to any outright abnormality of growth or development. PMID- 8484143 TI - A biomechanical analysis of short segment spinal fixation using a three dimensional geometric and mechanical model. AB - Vertebral stabilization using spinal fixation devices is a widely used technique. A three-dimensional geometric and mechanical finite element model has been used as a simulation tool for the evaluation of the mechanical behavior of spinal devices. The geometry of lumbar vertebrae was parameterized, which allows the construction of the geometric model for a given lumbar segment from the digitization of two roentgenographs. This procedure was used to construct a finite element model for a three-vertebra segment with simulation of fractures in the middle vertebra, and with simulation of a restoration using an osteosynthesis device, implemented in a frame fashion with four screws and two rods linked by two transverse rods, and/or an anterior bone graft. Compression force and torsion moment were considered, and different cases were investigated, by varying the severity of the fracture, the geometric characteristics of the device, and the mechanical characteristics of the material joining the two intact vertebral bodies. Results were analyzed considering the mobility of the vertebral segment, which indicates the ability of the restoration system to stabilize the vertebral segment, and considering the forces and moments distribution in the device, which gives information on part of the forces that pass through the device in each situation. Results show that maximum values of forces and moments in the device are more important in compression than in torsion. Adding an anterior bone graft has an effect mainly for compression, whereas in torsion its effect is negligible. For a rigid fixation device, no significant difference was found between different fracture models, indicating that the posterior arch does not play an important role for an instrumented segment. For compression, a rigid posterior wall, or the presence of a bone graft, reduces greatly the mobility of the instrumented segment. For torsion, suppressing the two transverse rods in the device greatly increases the mobility of the instrumented segment. Using a finite element model of a lumbar vertebral segment appears to be an interesting tool to analyze the behavior of an instrumented spine and to compare between different stabilization systems. PMID- 8484144 TI - Monitoring of the motor pathway during spinal surgery. AB - Paraplegia caused by irreversible lesions of the spinal cord is one of the major possible complications after scoliosis surgery. Several monitoring methods have been proposed but none are completely satisfactory. Since 1986 the authors assessed motor pathways during scoliosis surgery, using electrical stimulation of the motor cortex and lower limb muscle recordings (tibialis anterior muscle). Twenty-seven patients were included in this study: 25 with idiopathic scoliosis and 2 with dorsal kyphosis. Recordings in anesthetized patients with hypothermia were performed before and after spinal derotation during the surgical procedure. Magnetic cortical stimulation was carried out in ten awake patients before and after surgery. Reproducible responses were obtained in 22 patients under anesthesia. In eight patients no difference of the latency of the muscle response was detected before and after the correction of the spinal angulation. In 14 patients the increase of latency ranged from 0.4 ms to 5.2 ms. No correlation was found between the slowing of motor conduction and the magnitude of spine correction. No central neurologic complications were seen after surgery. The authors concluded that their study demonstrated that motor pathway assessment in anesthetized patients can be performed at different times during the surgical procedure. This technique should help in the future monitoring spinal function during scoliosis surgery. PMID- 8484145 TI - Magnetic stimulation for monitoring of motor pathways in spinal procedures. AB - Transcranial magnetic stimulation was used for intraoperative motor evoked potential monitoring during surgery of intramedullar, extramedullar, and extradural spinal tumors in 13 patients. Anesthesia was based on etomidate. Magnetic stimulation for motor evoked potential monitoring was successful in 10 of 13 patients, 12 of whom were neurologically impaired. Motor evoked potentials were recorded from limb muscles or from the fibers of the cauda equina. Amplitudes of baseline recordings (the initial recording obtained after induction of anesthesia) were decreased by 64 +/- 34% (mean +/- SD) and baseline latencies were increased by 7 +/- 8% compared with the preoperative recordings. Subsequent recordings were analyzed for amplitude and latency changes in comparison to baseline. Amplitude changes exceeding 50% and latency changes higher than 3 ms compared with the baseline correctly indicated an impending lesion of motor pathways with increased paresis postoperatively. In cases where motor evoked potential monitoring was successful prediction of short-term postoperative motor outcome was always correct. There were no "false-negatives" or "false-positives." PMID- 8484146 TI - Intensive dynamic back exercises with or without hyperextension in chronic back pain after surgery for lumbar disc protrusion. A clinical trial. AB - Sixty-two patients with chronic low back pain occurring 14-60 months after undergoing discectomy for the first time were randomized to two physical treatment groups: 24 sessions of intensive dynamic back exercises with hyperextension or 24 sessions of intensive dynamic back exercises without hyperextension. At the conclusion of therapy and at one-year follow-up, no difference was seen between the randomized groups, with regard to the combined assessments of pain, disability and objective measurements. A difference for back exercises without hyperextension to be superior to the other treatment regimen was statistically significant at the three-month follow-up. In the patient's qualitative assessment of treatment outcome there were seen no significant differences between back exercises with or without hyperextension. There was a similar and significant improvement of the isometric endurance of back muscles in both groups, but the flexibility of the spine was significantly improved only in the group using hyperextension exercises. The overall response rate of an earlier published investigation was reproduced. It is concluded that chronic back patients after first time discectomy may benefit from an intensive rehabilitation protocol including intensive exercises. The added use of hyperextension exercises does not confer any independent benefit. Furthermore, the training had to continue for more than 2-3 months before a statistical significant decrease in back pain was reported in the patient pain diary. PMID- 8484147 TI - The lumbar multifidus muscle five years after surgery for a lumbar intervertebral disc herniation. AB - Biopsy specimens of the lumbar multifidus were obtained from 18 patients with lumbar disc herniation at operation and after a postoperative follow-up period of 5 years. The structure and morphometry of the muscle fibers were analyzed and these data were compared with intraoperative biopsy results and the clinical outcome of the operation. The main findings were: 1) on the basis of occupational handicap score 10 patients belonged in the "positive" and 8 in the "negative" outcome group; 2) the intraoperatively recorded selective type 2 muscle fiber atrophy and the extent of pathologic inner structure changes both decreased in the "positive" outcome group, whereas they persisted in the "negative" group; 3) grouping as a definite sign of reinnervation was seen in only two versus four patients of the "positive" versus "negative" outcome group; 4) the relative amount of adipose tissue within the muscle decreased more markedly in the "positive" outcome group. The authors propose that both inactivity and axonal injury (mainly of neurapraxia type) contribute to the selective type 2 atrophy and inner structure changes in disc patients' multifidus muscle. These pathologic structural changes correlated well with the clinical outcome, and most importantly they are reversible and can be diminished by adequate therapy. PMID- 8484148 TI - Local denervation atrophy of paraspinal muscles in postoperative failed back syndrome. AB - Impairment and disability after back surgery is a common diagnostic and therapeutic problem. For the most part the reasons are unclear. Of 178 patients who had undergone laminectomies 2-5 years earlier, 14 patients with good recovery and 21 patients with poor recovery but no evidence of restenosis on computed tomography were selected by the Oswestry index. According to radiologic, neurophysiologic, and muscle biopsy evidence most patients (13 of 15 studied) suffering from the severe postoperative failed back syndrome had dorsal ramus lesions in one or more segments covered by the scar and local paraspinal muscle atrophy at the corresponding segments. Disturbed back muscle innervation and loss of muscular support leads to the disability and increased biomechanical strain and might be one important cause to the failed back syndrome. It may be possible to develop operating techniques that save back muscle innervation better than the usual ones. PMID- 8484149 TI - Lumbar muscle usage in chronic low back pain. Magnetic resonance image evaluation. AB - Methods for detecting recruitment patterns of the lumbar muscles during exercise in patients with chronic low back pain are limited. This article discusses the use of magnetic resonance imaging with Roman chair extension exercise to examine lumbar muscle usage in five normal volunteers, five chronic low back pain patients without surgery, and five chronic low back pain patients with surgery. Changes in signal intensities of psoas, multifidus, and longissimus/iliocostalis with graded exercise were measured at three lumbar disc levels. At rest, there was a difference between multifidus and longissimus/iliocostalis signal intensity in chronic low back pain subjects without surgery (P = 0.0162) and in chronic low back pain subjects with surgery (P = 0.0036), but not in normal subjects. At peak exercise, there was a difference in signal intensities between multifidus and longissimus/iliocostalis in all groups (normal volunteers, P = 0.0069; chronic low back pain patients without surgery, P = 0.0125; chronic low back pain patients with surgery, P = 0.0060). The exercise response was attenuated in chronic low back pain patients with surgery. Thus, MRI demonstrates static and dynamic differences in lumbar paraspinal musculature in chronic low back pain subjects compared to normal subjects. PMID- 8484150 TI - Primary prevention of back symptoms and absence from work. A prospective randomized study among hospital employees. AB - The personnel at a geriatric hospital were randomized into two groups. One group was allowed to exercise during working hours to improve back muscle strength, endurance, and coordination. The other group did not participate in the exercise program and received no further advice or information. After 13 months, the training group had increased back muscle strength. One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group (P < 0.004). The back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way. Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days, resulting in a cost/benefit ratio greater than 10. PMID- 8484151 TI - An epidemiologic study of non-occupational lifting as a risk factor for herniated lumbar intervertebral disc. The Northeast Collaborative Group on Low Back Pain. AB - An epidemiologic case-control study of herniated lumbar intervertebral disc was conducted in Springfield, Massachusetts, New Brunswick, New Jersey, and New York, New York, to evaluate the role of several possible risk factors in the etiology of this disorder. Patients with signs and symptoms of herniated lumbar disc (N = 287) were matched to control subjects without back pain by age, sex, source of care, and geographic area. Of the total case-subject group, 177 were confirmed by surgery, computed tomographic scan, myelogram, or magnetic resonance imaging. This article focuses on non-occupational lifting, an activity not previously reported on. Frequent lifting of objects or children weighing 25 or more pounds with knees straight and back bent was associated with increased risk of herniated lumbar disc. This association was particularly strong among confirmed case subjects (relative risk = 3.95). Positive associations among confirmed case subjects were also seen for frequent lifting with arms extended (relative risk = 1.87) and twisting while lifting (relative risk = 1.90). No associations were found for frequent stretching or carrying. If confirmed in other investigations, these data suggest that instruction in lifting techniques should be extended into the home. PMID- 8484152 TI - Quantification of trunk muscle performance in standing, semistanding and sitting postures in healthy men. AB - The purpose of this study was to determine trunk muscle performance in the sitting, semistanding, and standing postures during isometric and dynamic extension and flexion movements. Twenty-five male subject volunteers, with no previous history of back pain participated in the study. A triaxial dynamometer that measures torque, angular position, and velocity was used to measure isometric and dynamic motor output. The dynamometer allows testing in the sitting and standing postures. A custom-designed module also allowed testing in the semistanding posture. Each subject was tested in two sessions. The first session included the physical examination and three trials of isometric maximum voluntary contractions in the three postures. The second session included the dynamic performance against a resistance equal to 50% of the effort, as measured in the first session. Subjects were instructed to perform five repetitive flexion and extension cycles as fast and accurately as possible with maximum effort. An analysis of variance with repeated measures design was used to investigate the effects of the postures (standing, semistanding and sitting), the direction of exertion (flexion and extension), and the interaction effects of the isometric and dynamic parameters (maximum and average torque, velocity, power, and range of motion). The effects of direction (F = 98, P < 0.0001) and the interaction of posture and direction (F = 7.9, P < 0.001) were significant. The maximum isometric flexion strength was significantly higher in the standing posture than in semistanding and sitting. The maximum isometric extension was not affected by the posture (sitting, semistanding and standing).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484153 TI - Increased central drive during fatiguing contractions of the paraspinal muscles in patients with chronic low back pain. AB - In low back pain patients the paraspinal muscles demonstrate excess fatigability. Whether the cause is "central" as could result from impaired motor unit recruitment due to poor motivation or fear of pain, or "peripheral", and caused by defects in the contractile apparatus, is unknown. Using surface electromyography in conjunction with a standardized isometric fatigue test, this study investigates the mechanisms causing paraspinal muscle dysfunction in patients with both nonsurgical and postsurgical chronic low back pain. During the fatigue test normal subjects and both patient groups exhibited electromyographic increases. These were significantly greater in both patient groups, indicating increased central drive to their muscles. These findings may suggest that patients' excess fatigue is peripheral in origin, with increased central drive arising secondary to muscle wasting or denervation, although a central activation defect has not been excluded. Impaired physical performance in low back pain patients does not seem to be caused by lack of central drive. PMID- 8484154 TI - The role of dynamic three-dimensional trunk motion in occupationally-related low back disorders. The effects of workplace factors, trunk position, and trunk motion characteristics on risk of injury. AB - Current ergonomic techniques for controlling the risk of occupationally-related low back disorder consist of static assessments of spinal loading during lifting activities. This may be problematic because several biomechanical models and epidemiologic studies suggest that the dynamic characteristics of a lift increase spine loading and the risk of occupational low back disorder. It has been difficult to include this motion information in workplace assessments because the speed at which trunk motion becomes dangerous has not been determined. An in vivo study was performed to assess the contribution of three-dimensional dynamic trunk motions to the risk of low back disorder during occupational lifting in industry. More than 400 repetitive industrial lifting jobs were studied in 48 varied industries. Existing medical and injury records in these industries were examined so that specific jobs historically categorized as either high-risk or low-risk for reported occupationally-related low back disorder could be identified. A triaxial electrogoniometer was worn by workers and documented the three dimensional angular position, velocity, and acceleration characteristics of the lumbar spine while workers lifted in these high-risk or low-risk jobs. Workplace and individual characteristics were also documented for each of the repetitive lifting tasks. A multiple logistic regression model was developed, based on biomechanical plausibility, and indicated that a combination of five trunk motion and workplace factors distinguished between high and low risk of occupationally related low back disorder risk well (odds ratio: 10.7). These factors included 1) lifting frequency, 2) load moment, 3) trunk lateral velocity, 4) trunk twisting velocity, and 5) the trunk sagittal angle. This analysis implies that by suitably varying these five factors observed during the lift collectively, the odds of high-risk group membership may decrease by almost 11 times. The predictive power of this model was found to be more than three times greater than that of current lifting guidelines. This study, though not proving causality, indicates an association between the biomechanical factors and low back disorder risk. This model could be used as a quantitative, objective measure to design the workplace so that the risk of occupationally-related low back disorder is minimized. PMID- 8484155 TI - Measurement of vertebral foraminal dimensions using three-dimensional computerized tomography. AB - The dimensions of lumbar intervertebral foramina were measured in cadaveric spines using three-dimensional computerized tomography. Six different image reconstruction protocols were used. The results were compared with measurements of the same foramina using calipers after dissection. All the three-dimensional computerized tomographic measurements underestimated the true foraminal dimensions. The best agreement, as well as the best images, were obtained using 4/3 slices and a reconstruction threshold of 300 Hounsfield Units. This method is not recommended for measurement of foraminal dimensions. However, there may be a use in assessment and planning surgical management. PMID- 8484156 TI - Structural properties of the anterior longitudinal ligament. Correlation with lumbar bone mineral content. AB - The relationship between the amount of bone in the lumbar spine and ligamentous properties has not been studied. This article reports the tensile structural properties of bone-ligament-bone preparations of the anterior longitudinal ligament from 15 human lumbar spine segments. Significant correlations were found between the vertebral bone mineral content expressed as BMC (g/cm) and BMA (g/cm2) and BMD (g/cm3) and the structural properties of the vertebral bone anterior longitudinal ligament-bone complex determined at yield and failure. These findings suggest that the amount of bone tissue in the spine may be functionally related to structural properties of the spinal ligaments. PMID- 8484157 TI - A geometric model of the lumbar spine in the sagittal plane. AB - This article describes a geometric model using the skin profile and five anthropometric measurements to estimate the position of S1, T12, and all lumbar vertebrae for all postures assumed in the sagittal plane. This method involves a normalization process by which different skin profiles can be compared between postures and individuals. The skin profile is transformed by taking the differences with the lumbar spine into consideration. The model was developed and validated with 20 and 7 subjects, respectively. An error analysis shows an adequate level of accuracy for the absolute (1.68-1.82 cm) and relative (0.32 0.54 cm) linear positions of vertebrae as well as their absolute (2.6-6.7 degrees) and relative (1.4-3.6 degrees) angular positions except for T12; however, the validity of the model was limited to specific angular motions in flexion for the pelvis (12 +/- 3%), the entire lumbar spine (14 +/- 13%) and the intervertebral motion of L4/L5 (13 +/- 10%). The data obtained are very useful, especially in models designed to evaluate loadings on the lumbar spine. PMID- 8484158 TI - A poroelastic-swelling finite element model with application to the intervertebral disc. AB - The swelling process that occurs in soft tissue is incorporated into a poroelastic finite element model. The model is applied to a spinal segment consisting of two vertebrae and a single intervertebral disc. The theory is an extension of the poroelastic theory developed by Biot and the model is an adaptation of an axisymmetric poroelastic finite element model of the intervertebral disc by Simon. The model is completely three-dimensional although the results presented here assume symmetry about the sagittal plane. The theory is presented in two stages. First the development of the poroelastic theory. Following this, the effects of swelling caused by osmotic pressure are developed and expressed as a modification of the constitutive law and initial stresses. In the case of the disc, this pressure is produced mainly by the fixed negative charges on the proteoglycans within the disc. In this development we assume that the number of fixed charges remains constant over time and that the distribution of mobile ions has reached equilibrium. The variations over time in osmotic pressure, and thus in swelling effects are therefore only dependent on the initial state and the change in water content. Variations of the swelling effects caused by changes in mobile ion concentrations will be the subject of a future paper. The results reported in this article illustrate the dramatic effect of swelling on the load carrying mechanisms in the disc. The authors believe it is likely that this will have important useful implications for our understanding not only of normal disc function, but also of abnormal function, such as disc degeneration, herniation, and others. PMID- 8484159 TI - Spinal epidural abscess complicated closed vertebral fracture. A case report and review of literature. PMID- 8484160 TI - [Anterior cruciate ligament-plasty with the Insall iliotibial tract transfer. Long-term results after 5 years]. AB - For the reconstruction of the anterior cruciate ligament we performed the bone block iliotibial tract transfer in 56 patients from May 1984 until December 1987. The results were followed up for 2 to 6 1/2 years (average 53 months). The clinical results showed a positive Lachman test in 20 degrees flexion (3-5 mm) in 50% of the knees. There was no Lachman test ++ or and no sign of pivot shift. At the time of follow-up, the Lysholm-score was very high with 98.67 points. Subjectively, 91.3% of the knees were rated excellent, 4.3% good and 4.3% poor. 93% of the patients were engaged in some kind of sport before their accident, 87% of all patients were able to practice their sport at the same level after the operation. Long-term results after 5 years are consistent with the physiological aspects of this transfer. The immediate fixation of bone allows early motion of the knee and the rehabilitation time is much shorter. PMID- 8484161 TI - [Conservative therapy of ruptures of the medial collateral ligament of the knee. Results of a comparative follow-up study]. AB - The rupture of the medial collateral ligament of the knee joint due to sports injuries is the most common lesion of ligaments of the knee in athletes. The treatment is usually non-operative. We compared in a retrospective study the conservative treatment of these ruptures by two different methods. One group of patients was immobilised in a plaster cast for six weeks, one group of patients was partially immobilised with a brace, initiating early functional therapy. The results proved that the group of early mobilisation was significantly better in late results, in shorter rehabilitation and in all other aspects regarded as important for the treatment of such an injury. Therefore we feel the treatment with plaster casting for isolated ruptures of medial collateral ligaments as the knee should be abandoned. PMID- 8484162 TI - [Rehabilitation after cruciate ligament repair with the middle third of the patellar ligament in the athlete]. AB - Rehabilitation of athletes following surgical reconstruction of complex instabilities of the knee joint focuses on four goals: 1. the restoration of ligament stability, 2. the restoration of muscular stabilisation ability, 3. the restoration of coordinative muscular function in sport specific kinesiology, 4. the retention and improvement of the general state of fitness. These aims can only be reached by a close cooperation between physician, physiotherapist, trainer, and coach. In order not to put the rehabilitation process at risk, everybody involved has to have knowledge about functional anatomy, surgical technique, and biology of the transplant as well as knowledge about the long duration thereof that cannot substantially be shortened by knee ortheses. No athlete should compete until he has demonstrated sufficient fitness, strength, and coordination for his sport under laboratory conditions. PMID- 8484163 TI - [Control of the rear foot in lateral movements in sports]. AB - The goals of this investigation were to establish the frequency distribution of different movements in various ball sports (1) and to test the influence of altered shoe sole constructions on the stability in lateral breaking movements (2). Firstly, a video analysis was carried out to establish the frequency distribution of different movements in sporting activities such as volleyball, basketball, team handball and football (soccer). It is shown that a selected number of lateral cutting movements can represent more than half of all movements observed in one of the sporting activities. For part 2 an investigation with three systematically varied shoes was undertaken. The results show that with altered shoe sole constructions (torsion and change of shape of the shoe-sole) the supination movement with shoes comes close to the barefoot values. In respect of abduction/adduction of the foot the systematic changes of the shoe soles had no measurable influence. PMID- 8484164 TI - [Novel functional studies of the stabilizing behavior of ankle joint ortheses]. AB - For functional treatment of acute ankle sprain after surgical or nonsurgical management various special shoes and braces are in use. For a comparison under functional conditions we applied controlled inversion movements of 20 and 30 degrees to 13 subjects. The reduction of angular displacement was measured for the following orthosis: Aircast, Adimed Stabil 2, Adipromed Stabil Super, Mikros Ankle Brace, MHH-Splint Caligamed, Puschbrace and Tape. For evaluation of the neuromuscular activation surface EMGs of selected leg muscles were analyzed. A significant reduction of the induced inversion displacement was observed in all devices, although a complete inhibition of this movement was not possible. EMG activation was comparable to physiological conditions and is not correlated to the displacement characteristics. It is concluded that functional evaluation must take into consideration both the optimal reduction of the inversion and the high functional innervation. PMID- 8484165 TI - [Stress fractures of the tibia in nuclear magnetic resonance tomography]. AB - To demonstrate the usefulness of MR-imaging seven cases of suspected stress fractures are demonstrated and discussed (six stress fractures, one osteoid osteoma). The results indicate that stress fractures of the tibia may be differentiated early and easily from tumorous lesions, especially in atypical cases. In one case the fracture line could be detected only by MRI. In this respect, MRI is of high diagnostic value in differentiating unclear bone anomalies. PMID- 8484166 TI - [Early functional conservative therapy of fresh fibular capsular ligament rupture from the socioeconomic viewpoint]. AB - The expected direct and indirect costs following a fresh fibular rupture of the capsular ligament, and hence the socioeconomic burden on the patient, was investigated by a prospective randomised study comprising 120 males and females between 18 and 45 years of age. A comparison of three different conservative treatment methods A (immobilisation in a plaster cast for three weeks, followed by mobilisation with the aircast splint), B (mobilisation with the aircast splint) and C (Unna's paste dressing for two weeks with subsequent tape dressings and in each case immediate mobilisation) showed a significantly better stability after 6 months in the groups B (2.6 +/- 2.3) and C (3.6 +/- 3.8) than in A (4.8 +/- 3.5). The direct subsequent costs were also significantly lower in the groups B (DM 175.-) and C (DM 206.-) than in A (DM 340,-). Taking an average daily hospital care fee of DM 319.- (1991 in West Germany) as basis, the direct costs sequential to early functional treatment are the lowest also in comparison with surgical treatment in a hospital. The indirect sequential costs due to loss of working hours are mainly dependent on professionally conditioned physical stress but increase with the period of immobilisation after a fresh fibular rupture of the capsular ligament. PMID- 8484167 TI - [Comparison of combined extra- and intra-articular stabilization versus isolated arthroscopic semitendinosus repair after rupture of the anterior cruciate ligament]. AB - In a prospective study we examined 32 patients with a combined reconstruction of the anterior cruciate ligament, with arthroscopical use of a loop of semitendinosus tendon for the intraarticular portion and an iliotibial band tenodesis for the extraarticular augmentation in comparison to an isolated intraarticular semitendinosus reconstruction in 26 patients. Additionally the importance of a standardized rehabilitation program in this study was evaluated in comparison to a study on 58 athletes without standardized rehabilitation after an arthroscopic ACL-semitendinosus reconstruction. Lysholm-Score, clinical and radiological findings, KT-1000 stability values and isokinetic tests were evaluated monthly over a year. This data suggests that while both procedures under standardized rehabilitation conditions may obtain excellent functional results, adding the iliotibial band tenodesis to an intraarticular reconstruction significant improvement in stability and muscular strength was observed. Patients were able to resume all activities without pivoting. PMID- 8484168 TI - Threshold variation in automated perimetry. AB - A physiologic fluctuation in threshold levels exists in automated perimetry, which is greater in glaucoma and ocular hypertensive patients than in normal subjects. Fluctuation increases with greater eccentricity from fixation and in areas of reduced retinal sensitivity. Other factors related to automated perimetry testing potentially may influence threshold fluctuation including: a learning effect, reliability, pupil size, age, and the mode of stimulus presentation. Statistical software may aid in analyzing both the single field and the changes between successive fields. However, statistical programs cannot replace physician judgment, and all factors that may influence threshold levels should be considered when interpreting automated visual fields. PMID- 8484169 TI - Peripapillary hemorrhage. AB - On routine examination, a 61-year-old man was found to have a deep peripapillary hemorrhage surrounding his left optic nerve head. Further examination revealed a left sixth nerve paresis, a subtle right homonymous quadrantanopia, and jerky pursuit to the left. The diagnostic work-up was delayed by the patient because of business commitments. He returned confused and obtunded. Neuro-imaging showed a large frontal mass, which turned out to be an anaplastic astrocytoma. Diagnosis of the lesion had been obscured by three false localizing signs. Discussion deals with the definition of Terson's syndrome and the occurrence of peripapillary hemorrhages. Other causes of peripapillary hemorrhages are illustrated. PMID- 8484170 TI - Wegener's granulomatosis presenting with sclerokeratitis diagnosed by antineutrophil cytoplasmic autoantibodies (ANCA). AB - A 23-year-old male presented with bilateral sclerokeratitis. He reported recent bronchitis, sinusitis, dyspnea on exertion, hemoptysis, arthralgias and myalgias. Wegener's granulomatosis was diagnosed by a positive antineutrophil cytoplasmic autoantibody (ANCA) test and a nasal and subglotic biopsy showing granulomatous inflammation. Treatment with cyclophosphamide, systemic corticosteroids and trimethoprim/sulfamethoxazole resulted in resolution of the sclerokeratitis and remission of the disease. PMID- 8484171 TI - Conjunctival and uveal melanoma in the dysplastic nevus syndrome. AB - The dysplastic nevus syndrome was conceptualized in the late 1970s, and the subsequent proposal of a genetic relationship with ocular melanoma has stimulated debate in the literature which remains unresolved. We present the case of a 60 year-old man with histologically proven sporadic dysplasic nevus syndrome and a prior history of nine cutaneous melanomas, who developed a large, exophytic melanoma of the cornea and limbal conjunctiva. Cytogenetic analysis of this melanoma revealed a clonal 1;14 translocation. We believe this is the first reported case to use cytogenetic techniques in the analysis of conjunctival melanoma, either associated with dysplastic nevus syndrome or in isolation. We review the clinical literature as well as the cytogenetic and molecular genetic data related to the possible association of cutaneous melanoma, conjunctival and uveal melanoma and the dysplastic nevus syndrome. PMID- 8484172 TI - Symptomatic retrochiasmal lesions in multiple sclerosis: clinical features, visual evoked potentials, and magnetic resonance imaging. PMID- 8484173 TI - Expanding school-linked health services: a role for nurses? PMID- 8484174 TI - Legal issues for nurses. Document, document, document, document. PMID- 8484175 TI - Pharmacists administering meds? No! PMID- 8484176 TI - Gridlock? Try new paradigm. PMID- 8484177 TI - 12th National Congress of the Italian Society for the Study of Haemostasis and Thrombosis. Parma, Italy, September 27-October 1, 1992. Abstracts. PMID- 8484178 TI - [Can fertility in cattle be improved by administration of Gonadotropin releasing hormone (GnRH)?]. AB - In this article a review is given of the results obtained with gonadotrophin releasing hormone (GnRH) in the treatment of repeat breeder cows, cows used for embryo transfer and of cows in the early post partum period. It is concluded that the results of GnRh administration to repeat breeders is very variable. It is quite sure that the positive effect of GnRH, if any is so low that from an economic point of view, treatment, can not be advised. The usefulness of administration of GnRH to embryo-transfer cows is very doubtful. There are as many publications with positive as with negative results. The administration of GnRH in the early post partum period can not be recommended. With this 'therapy' conflicting results have been obtained and occasionally negative side effects have emerged. PMID- 8484179 TI - [Dehorning of calves and removal of teats]. PMID- 8484180 TI - [Lymphosarcoma in a horse]. AB - A sixteen-year old pregnant Dutch Warmblood mare was referred to the Faculty of Veterinary Medicine because of sluggishness since eight days. The main clinical features were depression, pale mucous membranes with petechiae, ventral oedema and fever. Haematological evaluation revealed severe anaemia (haematocrit 0.15 L.L.-1) and leukopenia (2.3 G.L-1 with 96% lymphocytes). There was no thrombocytopenia. The horse died following a hospitalisation period of six days. At necropsy a (multicentric) lymphosarcoma was found in the bone marrow with neoplastic infiltration of the kidneys. PMID- 8484181 TI - Dikke darm-diarree [Large intestine diarrhea]. PMID- 8484183 TI - Professional security notebook: workplace advocacy. PMID- 8484182 TI - [European registration of veterinary drugs]. AB - An overview is given for the harmonization of veterinary medicines in the EC. What is the influence of the review caused by this process on the existing veterinary medicines? Besides the role of the Committee of Veterinary Medicinal Products (CVMP) in the registration process of mutual recognition and central registration, the role of its working parties are dealt with. Also the consequences of the recent residue legislation on the basis of Maximum Residue Levels (MRL's) are discussed for as well the existing as the new products. Recently adverse events have to be reported too and evaluated by the authorities. Are all the member states ready for this task? The tasks and procedures of the future European Agency for the Evaluation of Medicines and the future registration procedures are also discussed. PMID- 8484184 TI - An efficient synthesis of 4 beta- and 6 alpha-hydroxylated bile acids. AB - An efficient method for the preparation of 4 beta- and 6 alpha-hydroxylated bile acids has been developed. It involved a highly stereoselective acetoxylation at the 4 beta and 6 alpha positions of 3- and 7-oxo bile acids, respectively, with lead tetraacetate in the presence of boron trifluoride etherate in acetic acid. Reduction of the resulting alpha-acetoxy ketones with sodium borohydride or tert butylamine borane complex, and alkaline hydrolysis, provided the desired bile acids in good yields. PMID- 8484185 TI - 18-Substituted steroids. Part 18. Chemical synthesis and mineralocorticoid activity of 2 alpha- and 2 beta-hydroxyaldosterone. AB - The 2 alpha-hydroxy and 2 beta-hydroxy derivatives of aldosterone have been synthesized chemically from aldosterone, after the earlier identification of 2 alpha-hydroxylated metabolites formed in liver. Both 2 alpha- and 2 beta hydroxyaldosterone are potent mineralocorticoids, with activities on the order of 1/10 that of aldosterone on the basis of a rat bioassay. PMID- 8484186 TI - Synthesis of novel 6-aza-B- and 11-aza-C-homoestranes as antifertility agents. AB - Reaction of 3,9 alpha, 17 beta-trihydroxyestra-1,3,5(10)-trien-11-one 17-acetate 3-methyl ether (3) with N3H-BF3 etherate leads mainly to lactam (4) along with the N-azido compound (5) as a minor product. Under similar conditions, 3,17 beta dihydroxyestra-1,3,5(10)-trien-6-one 17-acetate 3-methyl ether gives lactam (12) and the tetrazole derivative (9). Similar reaction of the diacetate (8) gives only the tetrazole derivative (11). Compounds 4, 6, and 10 prevent implantation in rats at 5-, 10-, and 5-mg/kg doses, respectively. Compounds 4, 6, 9, and 10 show significant estrogenic activity at the respective contraceptive doses. PMID- 8484187 TI - Effect of sterol biosynthesis inhibitor, SSF-109, on cholesterol synthesis in isolated rat hepatocytes. AB - The inhibitory effect of SSF-109 on cholesterol synthesis in isolated hepatocytes was studied using a radio-high-performance liquid chromatography system, and the results were compared with those of other inhibitors, triparanol and AMO-1618. SSF-109 caused accumulation of two trimethylsterols: lanosterol and 24 dihydrolanosterol. The distribution profile of [2-14C]mevalonate-originated radioactivity in cholesterol, lanosterol, dihydrolanosterol, 2,3-oxidosqualene, and squalene indicates that SSF-109 inhibits the 14 alpha-methyl demethylase activity. Triparanol accumulated the radioactivity of [2-14C]mevalonate in desmosterol and 2,3-oxidosqualene suggesting that triparanol inhibits sterol delta 24-reductase and 2,3-oxidosqualene cyclase. AMO-1618 caused enrichment of the radioisotope from [2-14C]mevalonate in 2,3-oxidosqualene but reduced it in squalene, suggesting that AMO-1618 acts on 2,3-oxidosqualene cyclase and some enzyme that catalizes a metabolic pathway between mevalonate and squalene. PMID- 8484188 TI - Bile acid transformations by Alcaligenes recti. AB - Metabolism of cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid by the grown cells of the bacterium Alcaligenes recti suspended in water was studied. Each isolated metabolite was characterized by the application of various spectroscopic methods. Cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid yielded methylated derivatives 3 alpha methoxy-7 alpha, 12 alpha-dihydroxy-5 beta-cholanoic acid, 3 alpha-methoxy-7 alpha-hydroxy-5 beta-cholanoic acid, 3 alpha-methoxy-7 beta-hydroxy-5 beta cholanoic acid, and 3 alpha-methoxy-12 alpha-hydroxy-5 beta-cholanoic acid, respectively. In addition, cholic acid furnished 7 alpha, 12 alpha-dihydroxy-3 oxochol-4-en-24-oic acid; chenodeoxycholic acid gave 7 alpha-hydroxy-3-oxo-5 beta cholanoic acid and 7 alpha-hydroxy-3-oxochol-4-en-24-oic acid while ursodeoxycholic acid yielded 7 beta-hydroxy-3-oxochol-4-en-24-oic acid and 3 oxochola-4,6-dien-24-oic acid. The formation of various metabolites showed that two competitive enzymic reactions, i.e., selective methylation of the 3 alpha hydroxy group and dehydrogenation in the A/B rings, were operative. The methylation process was found to be enzymic involving an S-adenosyl-L-methionine (AdoMet)-dependent methyl transferase, and this reaction appeared to be inhibitory to the process of degradation of the ring system. In the other reaction sequence, degradation of the ring system was initiated by dehydrogenation of the 3 alpha-hydroxy group. A 7 beta-dehydratase activity producing the delta 6 double bond was also noticeable in the metabolism of ursodeoxycholic acid. PMID- 8484189 TI - Stage-related changes in steroid-converting enzyme activities in Squalus testis: synthesis of biologically active metabolites via 3 beta-hydroxysteroid dehydrogenase/isomerase and 5 alpha-reductase. AB - To investigate the relationship between steroidogenesis and spermatogenesis, two key enzymes of androgen biosynthesis, 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) and 5 alpha-reductase, were compared at premeiotic (PrM), meiotic (M), and postmeiotic (PoM) stages. Staged tissues were obtained by dissection from the testis of the spiny dogfish Squalus acanthias, in which spermatogenesis is a simple diametric progression. Microsomal 3 beta-HSD activity was measured by conversion of [3H]dehydroepiandrosterone (DHEA) to androstenedione (AE). Reaction constants were: Km = 3.2 microM and Vmax = 243 pmol/min/mg protein. 3 beta-HSD increased progressively with maturation, resulting in three- to four-fold higher levels in PoM than in PrM stages. Absolute values and stage-related differences were the same, whether microsomes were derived from whole testis or from isolated spermatocysts (germ cell/Sertoli cell units), thus supporting microscopic studies showing that Sertoli cells are the primary steroidogenic elements of dogfish testis. In vitro conversion of [3H]testosterone to [3H]dihydrotestosterone (DHT) was used to estimate 5 alpha reductase activity. Apparent substrate affinity was similar to that of 3 beta-HSD (Km = 2.9 microM), but maximal product yields were two to three orders of magnitude lower (Vmax = 208 fmol/min/mg protein). Also, the stage-related pattern of 5 alpha-reductase activity (PrM > PoM >> M) differed from that of 3 beta-HSD (PoM >> M > PrM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484190 TI - [The elderly in 2005: healthy or in need of care?]. PMID- 8484191 TI - [Care requirements and psychosocial care problems in nursing homes]. AB - Residential homes were initially conceptualized to offer relatively independent elderly people room and board, rather than the nursing, medical, and rehabilitative care provided in nursing homes. Yet in the Netherlands an increasing number of frail elderly people are cared for in residential homes. By means of standardized rating scales data were collected in 1991 on the ability to perform 12 activities of daily living (ADL), cognitive disabilities, frequency of mood and behavioural problems, and social activities of all 1045 residents of 12 homes. The mean age of the 842 women (80.6%) and 203 men (19.4%) in this sample was 84.9 years (SD = 6.1). Using cutoff points that indicated the presence of serious impairment, we found that 11.9% of the residents were severely disabled in ADL. Severe cognitive impairments were detected in 10.2%, mood and behavioural problems in 13.7% and lack of social contacts in 11.6%. Multivariate cluster analysis revealed five patterns of care requirements, ranging from slight assistance (61.4%) to continuous skilled nursing care (4.9%). Residents are not homogeneous in their care requirements: 12.1% were found in a cluster that indicated a selective need of social contacts, 11.6% clustered together because of mood disorders, and 10.0% was found to have serious problems in three areas (ADL, cognition and social activity), except mood. This study suggests that about 15% of the elderly in residential homes need intensive and round-the-clock (psychogeriatric) nursing care. We conclude that residential homes have become a major component of the Dutch health care system for frail elderly patients. PMID- 8484192 TI - [Substitutes in care of the elderly? The artifact of a null correlation]. AB - On theoretical grounds or as a consequence of social policy measures (substitution), a negative correlation between formal and informal help is expected. A remarkable finding in most of the cross-sectional research is however a zero-correlation. Some researchers are tempted to conclude that substitution in care is not possible. In this article the composition of the population under investigation is suggested as an explanation for the absence of the correlation. If the population contains many young and healthy elderly, neither formal nor informal help is mostly necessary. The existing substitution in care for the needy elderly is consequently obscured and a zero-correlation between formal and informal help is found. This zero-correlation suggests that no substitution has taken place, but results from the composition of the population. In this article data on a life situation survey among 304 elderly people in a rural area are presented to illustrate this assumption. PMID- 8484193 TI - [A closer look at the Scale for Subjective Well-being of the Elderly]. AB - The Dutch Scale for Subjective Well-being of the Elderly (SSWO, 30 items) is a reliable and valid measure of well-being of the elderly. In this article, this instrument is subjected to a psychometric evaluation. First, as it is known that the SSWO has a weak subscale 'SSWO-Contacts', a new and reliable subscale 'SSWO Contacts' was developed. Four SSWO-items were replaced by six items from an existing and valid Loneliness-scale. Cronbach's alpha for the new subscale increased from .61 to .86. This also led to a slight increase in reliability of the new SSWO (32 items) as a whole from .88 to .90. Secondly, the hierarchical order of the items in the SSWO-subscales was tested with a Mokken-scaling procedure. Of the five subscales, four showed a (weak to rather strong) hierarchy. Thirdly, a short version (8 items) was developed to maximize the possibilities of implementing the SSWO. This short version has 85% of variance in common with the 32-item version. Validity of the SSWO-32 and SSWO-8 was explored by correlating the instruments with measures of health and personality. All expected relations were found. Also, the newly developed instruments proved to be reliable measures in a dataset of 119 elderly persons. The SSWO-32 is recommended for the investigation of specific dimensions of well-being in elderly people. The SSWO-8 can be used to obtain a quick and global impression of well-being. PMID- 8484194 TI - [Comprehensive care for the elderly in The Netherlands: current status and potential improvements]. AB - Family care is important for older people who are in need of some kind of care and who live in their own home. Sometimes support from services for family caretakers is essential for them to continue caring. The existing possibilities to get this support are not sufficiently available in the Netherlands: if someone is in need of support at the emotional, practical or material level, services are scarce. In order to change this situation, some recommendations are made. A change in attitude towards family caregiving is the most important one. PMID- 8484195 TI - Ultrasound scattering properties of Albunex microspheres. AB - Albunex is an ultrasound contrast agent used in echocardiography and in other areas, it consists of microspheres of which more than 95% have a diameter in the range 1-10 microns. The scattering properties of this agent as functions of ultrasound frequency and microsphere diameter and concentration are investigated. A model of the Albunex microspheres has been previously described, considering the individual microspheres as air bubbles surrounded by a thin elastic shell. In the present study this model is extended by including into it the internal friction in the shell when the microsphere vibrates. Acoustic scattering and transmission are measured in the frequency range from 700 kHz to 12.5 MHz. The measured transmitted power is used to estimate the two parameters in the theoretical model: the shell elasticity parameter, Sp and the shell friction, Sf. Introduction of the shell friction into the model improves the agreement between theory and measurements. For the scattered power, differences between measured and calculated values lie within 3 dB. It is concluded that for the frequencies 2.5 and 5 MHz, microspheres with a diameter between 5 and 12 microns are preferred as these deliver the most significant contribution to the total scattered power and cause relatively little attenuation. PMID- 8484196 TI - [Expert commissions and arbitration boards. A report of current status]. AB - Since 1975 all German Land Medical Councils (Landesarztekammern) have launched either boards of experts or arbitration panels with the intention to settle disputes on medical malpractice by arbitration, on a voluntary base, free from commitment, and without any costs for the parties concerned. Numbers of arbitrator's awards and rates of affirmed cases of malpractice are given for the years 1988 to 1991, for all panels or boards, respectively. More details are reported from the boards of experts of the Land Medical Council of Baden Wurttemberg with special reference to possible relations of affirmed awards to some demographic and professional factors. The probability of being involved in a procedure of arbitration is broken down by medical specialty and by site of employment, e.g. in hospital or in medical practice. The highest rates are found in specialties operating on and in hospital doctors. But the percentage of affirmed awards is higher for doctors working in their own office. Evaluating the consequences following the awards of two different periods shows a high degree of acceptance by the patients. Without affirmation less than ten percent of all patients involved apply to the courts but this is done by about thirty percent if the award is affirmating. In these cases the amount of the compensation wanted is contested. PMID- 8484197 TI - [Nursing care insurance--facts and prognosis]. AB - There are in the Federal Republic of Germany at present 2% of the population "needing care" (80 m/1,65 m), 450,000 citizens are getting now in-patient treatment, 1.2 m are being looked after in family circles. The public opinion dilemma (rise in the rate of old people to the total population--declining birth rate) will be in 2010 so marked, that the number of people needing care will rise to 3.5 m. 85% of these patients will be then past 65 years. At the moment social discussions of drafts regarding financial guaranty for nursing, questions of infrastructure and compassion of the welfare are partly controversial. Unanimity has been reached, that prevention, active treatment and rehabilitation must be intensified before the onset of the nursing requirements is initiated. The paper informs of the actual making-up of the people's mind. Preliminary works regarding a statutory regulation for a welfare guaranty should be settled by the end of 1992. PMID- 8484198 TI - [Cost development in health care with special reference to unconventional procedures]. AB - The cost of healthcare continues to escalate. At the same time alternative medicine is becoming more popular. Therefore it seems necessary to consider the price of unconventional therapies: they are more expensive than generally supposed. The reasons are distinct modes of therapy, polypragmasy, long term therapies, and consecutive costs. Finally there is the question, whether it is ethical to ask for the cost efficiency ratio in the treatment of seriously ill. PMID- 8484199 TI - [Freedom to cure and alternative medicine]. AB - The problem area of unconventional methods of treatment involves addressing a complex web of legal questions (constitutional law, criminal law, medical liability law, social insurance law, medical professional law). However, proceeding from the basis of statutory health insurance law, all individual questions can be resolved uniformly if the customary statutory or contractual "scientific-basis-clauses" intended to restrict the use of unconventional methods of treatment are understood merely as a criterion for a medical-acceptability test that respects the individual physician's discretion as regards treatment and appraisal. Methods of "outsiders" are then not generally excluded; rather, an individual weighing-up of the benefits has to be carried out in each case. PMID- 8484200 TI - [The environment and health. Environmental pollution and its health effects]. AB - Both environment and health are terms of far-reaching meaning, which impedes a complete survey of their interactions. Originating from considerations about global phenomena, as e.g. the extinction of biological species, of the so called "forest dying", or of the extensive consumption of energy and material resources, on the hierarchy of effects on health of environmental damages on one hand or on the undisputable adaptivity of man in particular on the other, only actual examples are outlined. The groups of dioxins, asbestos and radon are outlined, considering them as representatives for the vast number of substances potentially harmful to the environment and for the complexity of the toxicological and oecological interactions with oecosphere, biosphere and man. By the examples, the principles of toxicological/oecological thinking are explained, finally never resulting in yes/no alternatives, but in compromises by sober balances of risk and benefit. The basically correct vigilance of the public against avoidable risks may not lead to hysteric reactions, impeding the concentration onto necessary and practicable solutions. PMID- 8484201 TI - [Death in bronchial asthma. Findings and forensic importance]. AB - In 23,707 forensical and 25,564 clinical post-mortem examinations a total number of 196 deaths from bronchial asthma were determined retrospectively. Furthermore investigated were 29 cases in which asthma had the importance of a pathological side finding. Described are the histories, epidemiological data as well as morphological and histological findings. The characteristic morphological triad of thickening of the epithelial basement membrane, hypertrophy of the muscle coat in the bronchi and mucus plugging were found in almost all cases of asthma death. Regarding to forensical and insurance medical aspects it is important to consider the accompanying circumstances and supporting facts of the death, therapeutical procedures and death causing concurrent non-natural organ damages. They form the basis for reproaches in terms of neglected help or accidental homicide and can call the way of death in question,--which is illustrated in examples. PMID- 8484202 TI - [Seat-belt syndrome. Is "securing" children in back seats of cars exclusively with a lap belt defensible?]. AB - In automobile accidents the "seat belt syndrome" describes a combination of injuries involving the thoraco-lumbar vertebrae and intraabdominal organs. This may result from wearing of only a pelvic seatbelt. Children are often involved. Analysis of two separate cases showed the "assurance" of children as passengers on the backseat with a pelvic belt to be dangerous and not longer justifiable. Anatomical proportions and posture in childhood necessitate backseats especially designed for children. They should include the possibility of installing a three point safety belt system. PMID- 8484203 TI - Biochemistry of the nematode cuticle: relevance to parasitic nematodes of livestock. AB - The cuticle of nematodes is a thin, flexible outer covering composed primarily of protein with trace amounts of lipid and carbohydrate. There has been considerable recent interest in the biochemistry, immunology and molecular biology of the cuticle of parasitic nematodes because of its role as an interface between parasite and host. The cuticle consists of: (1) collagen-like proteins that form the medial and basal layers; (2) non-collagen proteins that form the epicuticular and external cortical regions; (3) non-structural proteins associated with the external surface. The collagen-like proteins are solubilized by reducing agents, have molecular weights of 30-120 kDa and exhibit stage and species variations. Nematode collagen genes, however, code only for proteins with molecular weights of 30 kDa. The non-collagenous proteins, referred to as cuticlin, exhibit unusual chemical properties as indicated by their resistance to solubilization even under strongly denaturing conditions. Recent studies of Ascaris suum have demonstrated the presence of tyrosine-derived cross-links, dityrosine and isotrityrosine, that may form the linkage between subunits in assemblage of the collagenous and noncollagenous structural components of the cuticle. A peroxidase enzyme has been implicated in the synthesis of these cross-links. Recent 125I labeling studies of Haemonchus contortus have identified and characterized stage-specific proteins on the cuticular surface. PMID- 8484204 TI - Anthelmintics. AB - Anthelmintics remain the principal means for the prevention and control of subclinical and clinical ostertagiasis. The selection of an appropriate anthelmintic depends on whether one is controlling or preventing Type I ostertagiasis (caused by the establishment of adult worms derived from recently acquired infective larvae), preventing Type II (treating pre-Type II or inhibited larvae) or controlling Type II ostertagiasis (caused by the development of inhibited larvae to adults), or using the anthelmintic as part of an epidemiologically based plan to reduce pasture contamination with infective Ostertagia ostertagi larvae. In the latter case, the choice of an anthelmintic may depend on whether the targets for treatment are only adult worms and developing larvae or whether the targets include hypobiotic larvae. Thus for Ostertagia control, anthelmintics must be divided into those that normally control all stages, such as the avermectin group (ivermectin, abamectin and moxidectin) and some of the benzimidazoles (albendazole, oxfendazole and fenbendazole at appropriate dose rates), and those that only control adult worms and developing larvae (levamisole, morantel, coumaphos, phenothiazine and thiabendazole). PMID- 8484205 TI - Anthelmintic resistance. AB - In populations of livestock in which anthelmintics have become the only means of control, individual worms in some species of helminths evade the effects of specific anthelmintics. If these resistant individuals are selected (by removing the susceptible individuals in the population) then the resistant worm population on individual farms becomes dominant in both numbers and effect. This selection of anthelmintic resistant populations is most often reported in equids and small ruminants (the hosts in which anthelmintics are used most frequently). There is little evidence of anthelmintic resistance by Ostertagia in cattle but an understanding of the problem in other grazing species may aid in delaying its onset. Benzimidazole/phenothiazine resistance by small strongyles in horses in widespread. Resistance by various geographic strains of Haemonchus, Teladorsagia and Trichostrongylus against all of the commonly used classes of anthelmintics in small ruminants has been verified. The failure of levamisole to remove adult Ostertagia ostertagi from cattle has been reported in several geographical areas. Resistance is an individual farm problem and each premise has to be evaluated as to which anthelmintics can be used. Drug rotation, especially rapid rotation (less than 1 year) selects for multiple drug resistance. Epidemiologic treatment selects for resistance, but if properly used, requires considerably fewer treatments to prevent disease and the development of resistant populations will be slowed. A combination of strategic and tactical treatments along with evaluation of anthelmintics will be required to enable producers to raise livestock in maximum production units. PMID- 8484206 TI - Control strategies to prevent resistance. AB - Anthelmintics will continue to play a central role in nematode control programs of livestock for the foreseeable future. However, to prevent the emergence of resistance, anthelmintics need to be either so effective that there are no survivors following treatment or treatment should be so infrequent that those that survive make little or no contribution to subsequent generations of the parasite populations. In this regard, the record for the sheep, horse and particularly the goat industry is not good, whereas the second factor is almost certainly responsible for the lack of a significant resistance problem in the cattle industry. In Australia, where high levels of resistance prevail, control programs designed to limit the increase and spread of resistance have been promoted for some time. However, their development, and certainly their implementation, has tended to be reactive rather than proactive--attempting to deal with the problem when it threatens future productivity, rather than preventing it in the first instance. Regions and/or livestock industries with relatively less of a resistance problem should heed these developments and endeavour to establish a responsible ethos amongst users of anthelmintics. In concert with the general philosophy of Integrated Pest Management (IPM), parasite control schemes should focus on the planned integration of a range of techniques, rather than relying almost entirely on anthelmintics. By these means, sustainable control strategies to prevent resistance could be achieved. PMID- 8484207 TI - Pathophysiology of infection with Ostertagia ostertagi in cattle. AB - Infection with the abomasal nematode, Ostertagia ostertagi, is an important cause of impaired productivity in young cattle in temperate parts of the world. Such losses have been associated with marked changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and in body composition. The reduction in feed intake is an important factor in the pathogenesis of infection and may account for a large part of the difference in weight gain between ad libitum fed control and infected calves. Despite the obvious importance of inappetance, only recently has an association been made between reduced intake, altered gut motility and elevated levels of certain gastrointestinal hormones, such as gastrin. It has been suggested that the elevated gastrin levels accompanying abomasal parasitism may impair reticulo-ruminal motility and slow down abomasal emptying, leading to a stasis of ingesta and a reduction in feed intake. The rise in blood gastrin levels may also be partly responsible for the marked hyperplasia of the fundic mucosa seen in abomasal infections. Pronounced changes in protein metabolism have also been associated with Ostertagia infection. Radioisotopic studies have demonstrated increased losses of albumin into the gastrointestinal tract which are accompanied by an increase in the rate of synthesis in the liver. Dietary protein breakdown in the abomasum is also likely to be impaired, although there is evidence of a compensatory increase in protein digestion in the lower gut of parasitised calves. Increased losses of albumin are not always accompanied by increases in faecal nitrogen, suggesting that albumin is broken down and recycled as ammonia. Radioisotopic studies in animals with intestinal nematode infections have demonstrated a marked reduction in muscle protein synthesis and an increase in protein synthesis in gastrointestinal tissue. Such changes in the balance of protein synthesis are likely to be brought about by alterations in the balance of certain metabolic hormones. Marked changes in energy metabolism also accompany Ostertagia infection. Parasitised calves exhibit a marked increase in non-esterified fatty acid levels, resulting from the mobilisation of adipose tissue, and a reduction in digestive efficiency of energy, probably associated with the increase in cycling of protein through the gastrointestinal tract and the compensatory increases in protein synthesis. Mineral metabolism may also be affected although relatively little work has been conducted in cattle. Changes in body composition reflect a reduction in deposition of muscle protein and fat, and an increase in bone content and water retention. PMID- 8484208 TI - Economic benefits of parasite control in cattle. AB - The economic losses often associated with parasitism in cattle are universally accepted. The degree of economic significance related to these losses, the burdens of parasites required to cause such losses, and the specific control measures needed to avoid these losses are, however, topics of serious debate and outright disagreement among parasitologists and veterinarians. This is because most cattle have parasite burdens that are truly subclinical, with no obvious signs of parasitism but significant losses in potential production. These losses are often very insidious in nature and often difficult to prove statistically in a consistent manner. This discussion focuses on the need to: (1) define the benefits related to parasite control in cattle; (2) develop clear and effective parasite control recommendations that will allow the producer to realize these benefits; (3) effectively transfer this information to the cattleman. PMID- 8484209 TI - Evaluation of pepsinogen, gastrin and antibody response in diagnosing ostertagiasis. AB - Ostertagia ostertagi is widely distributed and is one of the most important parasites affecting young bovine livestock. There is, therefore, a substantial need for sensitive and specific parameters in support of diagnosis of ostertagiasis, especially for subclinical disease related to production losses. In this review, the value and application of pepsinogen, gastrin and antibody response as diagnostic tools are discussed. These three parameters are useful and comparable for confirming clinical disease in calves during their first grazing season. However, their value for detecting subclinical parasitism is questionable. Differences in the course of gastrin and pepsinogen late in the grazing season can be correlated with larval inhibition and the possibility of ostertagiasis Type II. Relatively few serological methods have been developed for the immunodiagnosis of Ostertagia and until now the indirect antibody-detecting enzyme-linked immunosorbent assay (ELISA) has been the method of choice. Antibody measuring methods have several disadvantages, most notably a lack of sensitivity and specificity, which limits their use in longitudinal epidemiological studies. Considering the necessity of cost effectiveness and ease of use, it is anticipated that additional work will result in the enhancement and quality of current immunodiagnostic methods. PMID- 8484210 TI - Estimation of the numbers of trichostrongylid larvae on pastures. AB - Estimates of the density of larvae on herbage are used in epidemiologic studies to determine seasonal or monthly variations in contamination of pastures with third-stage larvae of the trichostrongyles, and to provide an index of the risk of exposure of grazing animals. Estimates of density are affected by many variables, including laboratory techniques, climate, forage types, and farm and animal management methods. Thus, a comparison of results given by different workers is not desirable. In obtaining and interpreting larval density estimates, it is important to standardize the technique over the period of observation. Because techniques for estimation of larvae are cumbersome and time-consuming, statistical design is often compromised. Herbage samples should be taken randomly and with sufficient replication to overcome the variability of the herbage sampling technique. Studies to determine an appropriate sampling design to obtain the best estimate for pastures of all sizes have not as yet been carried out. PMID- 8484211 TI - Notes on necropsy and herbage processing techniques for gastrointestinal nematodes of ruminants. AB - Necropsy techniques for the digestive tract of ruminants used at the University of Utrecht differ from those used elsewhere in three respects: (1) the abomasum is opened immediately after slaughter and the "contents" are treated separately from the "washings"; (2) the first 10 m of the small intestine are treated separately from the remainder of the intestine; (3) the aliquots are coloured with iodine before being examined for worms. The majority of the worms are found in the washings of the abomasum and the first part of the small intestine, whereas the contents of the abomasum and the remainder of the small intestine contain the bulk of the digesta. Because inhibited stages of Ostertagia, Haemonchus and, particularly, the very small third stage larvae (L3) of Trichostrongylus can be overlooked easily in digesta, these methods imply a more rapid and accurate enumeration of worms. This is more important in small ruminants than in cattle because a much higher proportion of the inhibited larvae will be washed out of the mucosa and because Trichostrongylus is more important in small ruminants. Herbage sampling methods for monitoring gastrointestinal nematode infections on cattle pastures in northwest Europe should also be suitable for lungworm. The agar-bile technique of Jorgensen is an elegant method, but disadvantages are that many gastrointestinal nematode larvae exsheath, resulting in identification difficulties, and recovery of lungworm larvae decreases as a result of ageing. A simple sucrose flotation method, based on the principle that a sucrose solution does not mix easily with water containing nematodes, has been tested at our laboratory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484212 TI - Effects of grazing management practices on parasite load and weight gain of beef cattle. AB - Stocking rate, method of grazing (rotational vs. continuous) and supplementation are three grazing management variables which strongly affect weight gain of beef cattle. However, reports on the interaction between these variables and parasitism in beef cattle are often conflicting or not conclusive. Although several studies have shown increased parasite loads with increased stocking rates, few studies have included animals treated and untreated with anthelmintics at several stocking rates. Those that did have this treatment combination did not show greater response in weight gain to treatment with anthelmintics at high stocking rates than at low stocking rates. Experiments designed to investigate the effect of rotational and continuous grazing on parasitism have provided variable results. However, as the high stock densities associated with rotational grazing will probably cause animals to graze closer to the ground and to dung pats, and to spread dung more with their hooves, it is not likely that rotational grazing will reduce the need for chemotherapy. Some studies have shown reduced parasite loads with supplementation of untreated animals, but none has apparently investigated whether weight gain response to treatment with anthelmintics is greater for non-supplemented animals than for supplemented animals. Published studies on the interaction between management factors and parasitism in grazing animals reveal many weaknesses. Elimination of these weaknesses and cognisance of recent trends in design and conduct of grazing experiments will substantially improve the quality and value of research in this field. PMID- 8484213 TI - Gastrointestinal nematode infections and weight gain in dairy replacement stock: first-year calves. AB - For the evaluation of control strategies against, and economic impact of gastrointestinal nematode infection, the quantitative relationship between level of exposure to infection and growth performance is important. Available data in the literature are summarised. Based on questions derived from earlier work concerning the relationships between infection, growth performance and acquired immunity during the entire rearing period, two experiments were set up. In these experiments, groups of calves were exposed to different levels and patterns of infection with Ostertagia ostertagi and Cooperia oncophora. The experimental design simulated the stereotypic pattern of herbage infestation under conditions of set-stocking. A significant negative linear relationship between the level of exposure and growth performance was found (P < 0.001). The time sequences observed for body weight changes in response to infection and the magnitudes of the effects of infection on weight gain in both experiments suggested a good predictability of the relationship between infection and growth performance. By comparison, it is also suggested that in the Netherlands parasite control is excessive in the first grazing season. A more limited use of anthelmintic treatments is proposed. PMID- 8484214 TI - Control of gastrointestinal nematodes in Australia in the 21st century. AB - Because the Australian livestock industries rely overwhelmingly on year-round grazing of pastures, nematode parasites are of major concern. Nematode parasitism is recognized as the cause of the most economically important diseases of sheep, while in cattle, the relative importance of nematode parasitism will probably increase following the eradication of diseases such as brucellosis and tuberculosis. The extraordinarily high prevalence of resistance to benzimidazoles, levamisole and morantel in nematodes parasitising sheep has stimulated the formulation and, to a surprisingly large extent, adoption by farmers of strategic control programmes aimed at preserving the useful life of ivermectin. Even so, it is highly likely that we will enter the 21st century with ivermectin resistance. Current research aimed at control in the next century is progressing in three broad directions. First, towards better control using existing anthelmintics through modifications to pharmacokinetics, together with integrated management aided by computer simulation models of nematode population biology. Secondly, towards immunological control arising from a better understanding of the ruminant immune response to helminths, particularly in young animals, and finally, a coordinated investigation of genetic resistance, within breeds, of sheep to nematode parasitism. The appearance in the 21st century of novel anthelmintic compounds, most probably as a result of research by the international pharmaceutical industry, may well reduce the sense of urgency driving current Australian research. Nevertheless, success in one or more of these three lines of endeavour will mean a longer and more profitable life for the next generation of anthelmintics marketed in Australia. PMID- 8484215 TI - Mathematical models for the population biology of Ostertagia ostertagi and the significance of aggregated parasite distributions. AB - Parasite frequency distributions are frequently aggregated. Such distributions are conveniently described using the negative binomial frequency distribution. This distribution is completely characterized by two parameters: the mean of the distribution and an exponent, k. The degree of aggregation is inversely proportional to the value of k. Aggregated parasite distributions enhance the ability of regulatory processes to maintain parasite populations at or near their equilibrium level but incorporating parasite frequency distributions in realistic models of parasite population biology is fraught with difficulty (several simplified examples are given). Indeed, it is not always possible to incorporate parasite frequency distributions and the question arises whether this compromises model performance. Trichostronglyid nematodes, including Ostertagia ostertagi, are aggregated but the estimated value of k for such populations is usually greater than 1. This is typical of populations with high population means (tens of thousands). It is shown that when the degree of aggregation is such that k > 1, the results of a model which recognizes parasite frequency distribution is not much different from the results of a model which assumes all hosts contain exactly the same number of parasites. PMID- 8484216 TI - The role of inhibited development in the epidemiology of Ostertagia infections. AB - Seasonal patterns of inhibited larval development have been described for Ostertagia spp. from many parts of the world; winter inhibition is found in areas where transmission of infections occurs mainly in summer and summer inhibition in areas where transmission is mainly from autumn to spring. There is no fixed regional seasonal inhibition pattern. Depending on weather and farm management, the timing and level of inhibition will vary from year to year. Moreover, differences in the propensity for inhibition have been observed between field strains of Ostertagia in cattle in Australia and in the Netherlands. Simultaneous resumption of development of large numbers of inhibited larvae can result in Type II ostertagiasis, usually in only part of the heard. For reasons as yet unknown, there appear to be differences between regions in the prevalence of this disease. Development of immunity is also involved in the onset of inhibition and the occurrence of two separate inhibited populations in one host population, "seasonal" and "immunological", has been suggested. Seasonal fluctuations in the proportion of inhibition in naturally infected animals do not necessarily imply that the main trigger for inhibition is environmental conditioning, because infection levels and thus the degree of immunity will also fluctuate seasonally. In some Ostertagia field populations during late autumn in the Netherlands, worm burdens of permanently grazed calves consist mainly of inhibited larvae, but burdens of tracer calves consist of adults. Inhibited larvae may also be involved in the development of immunity. Some protection against reinfection with Haemonchus contortus has been demonstrated in barren ewes infected 6 months earlier with a single dose of 15,000 inhibition-conditioned larvae. Such an immunogenic role may be more important in Ostertagia, because inhibited larvae are found deeper in the mucosa than those of Haemonchus. PMID- 8484217 TI - Ostertagiasis in the cow and weaned calf in the northeastern USA. AB - Most gastrointestinal nematode infections of cattle in the northeast USA are combinations of Ostertagia ostertagi and Cooperia oncophora. These infections are usually of little consequence in adult cattle because of immunity and consequent low levels of infection. Some work has been done on the effects of infection on milk production but the results are equivocal. Clinical ostertagiasis in calves can lead to mortality. Such outbreaks are often associated with situations where calves are pastured at an early age onto special calf pastures that are used consistently for this purpose. Subclinical ostertagiasis is more usual in this region where light infections become established in calves with no obvious clinical signs. Such infections exact a toll on productivity in the form of decreased weight gains, decreased carcass quality, reduced nitrogen balance and negative effects on post-absorptive protein metabolism. Subclinical infections can also cause transient suppression of cell-mediated immune responses in calves. Increases in fecal worm egg counts of cows have been shown to occur during the spring months and these may contribute to increased contamination of pastures. Ostertagia infective larvae overwinter successfully on pasture and can persist until midsummer. Typical egg production patterns in calves involve a prepatent period, after introduction to pasture in mid to late May, of approximately 3 weeks. Peak egg production occurs at about 6-8 weeks and is followed by a gradual decline in egg counts into the fall. Hypobiosis is very apparent in this region and is most pronounced in late fall (October-November).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484218 TI - Epidemiology of Ostertagia ostertagi in cow-calf herds in the southeastern USA. AB - Ostertagia ostertagi is commonly found in the brood cow and nursing calf in the southeastern USA, this information being derived from fecal egg counts, coproculture and necropsy results; however, clinical disease and large burdens of this parasite are rarely reported. Fecal egg counts in brood cows are routinely low and are generally reported to be 10 eggs per gram of feces (EPG) or less. Nematode egg counts in spring-born calves are also generally low prior to weaning; they increase steadily during the spring and summer and peak from late summer to fall weaning. That egg counts in spring-born calves are low for several months after birth is probably a reflection of minimal grazing activity. It appears that Ostertagia ostertagi may be of equal or less importance than other nematode genera for spring-born calves in the southeastern USA. The role that Ostertagia ostertagi plays in fall-born calves or in year-round calving herds has not been adequately investigated. Also, the role that the adult cow plays, with low egg counts and small Ostertagia ostertagi burdens, in contamination of pasture is not understood during either lactation or dry periods. Treatment of beef calves prior to, or at weaning can reduce contamination and transmission of gastrointestinal parasites on pastures which may be subsequently grazed by these or other weaned calves. Data on parasite population dynamics from tracer calf studies in cow-calf herds in the southeastern USA have identified peak periods of transmission and incidence of specific genera or stages. This information, in conjunction with routinely used cattle production and management practices such as time of calving, should provide means to more accurately define optimal timing for strategic parasite treatment programs and their overall effect on beef production in the southeastern USA. PMID- 8484219 TI - Observations on nematode parasitism in cow-calf production systems in southcentral/southwestern USA. AB - Observations on fecal egg count (FEC) and nematode identification data were compiled to help determine the extent of nematode parasitism in cows and their nursing calves. Overall mean FEC values for cows in Utah, Louisiana, Nevada, Texas, and California were 7 eggs per gram (EPG), 6 EPG, 9 EPG, 10 EPG, and 15 EPG, respectively. Overall mean FEC values for nursing calves from the same states were 7 EPG, 228 EPG, 3 EPG, 60 EPG, and 398 EPG, respectively. The overall mean FEC value for Arizona cows was 33 EPG. Relatively complete seasonal FEC data were available from California and Louisiana where fall-born calves acquired high nematode burdens (i.e. 400-500 EPG) as early as 3 months of age, and spring-born calf FEC started low (10-30 EPG) and reached high levels (200-400 EPG) at about 5 months of age. In California, tracer calf data indicated that Ostertagia and Cooperia were the predominant nematodes acquired from pasture. In Louisiana, tracer calf, tracer cow, slaughtered calf (at weaning) and coproculture data indicated that Ostertagia (fall/winter) and Haemonchus (summer/fall) were the predominant nematode genera acquired by cows and that Ostertagia (winter/spring), Haemonchus (summer) and Cooperia (all seasons) were the predominant nematode genera acquired by calves. The acquisition of nematodes in tracer cows was much lower than in calves; however, the percentage of inhibited Ostertagia (ranging from 0% in summer to more than 80% in spring) was similar. A survey of abomasal nematodes in culled dairy and beef cows in Louisiana indicated that cows can harbor large (mean of 24,543 for beef and 16,383 for dairy) burdens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484220 TI - Epizootiology of Ostertagia ostertagi in cow-calf production systems in the American Midwest. AB - The most common gastrointestinal nematodes found in cattle in the Midwest are Ostertagia ostertagi and Cooperia oncophora. Other parasites include Haemonchus placei, Bunostomum phlebotomum and Nematodirus helvetianus. Parasite numbers are generally low in this region, as indicated by fecal egg counts and tracer calf worm recoveries, and the numbers of parasites decrease as one travels farther north. This decrease in parasite numbers also corresponds to a similar reduction in the prevalence of clinical disease. The dynamics of fecal egg shedding are similar throughout the Midwest. Cow fecal egg counts begin to increase just prior to calving in the spring, continue to rise, reaching a peak in July and August, and return to low numbers (2 or less eggs per gram of feces (epg)) in October. Calves born in the spring (March-May) show increasing numbers of eggs in their feces throughout the grazing season, with peak recoveries in October and November, after which the numbers decline as the calves develop an immunological response. Tracer calf worm recoveries demonstrate pasture contamination for the period grazed. These recoveries show adult O. ostertagi increasing throughout the grazing season then falling to low levels over the winter. Larval inhibition of O. ostertagi, as shown by recovery of inhibited fourth stage larvae (L4) occurs throughout the year, with increasing numbers of larvae recovered in the fall. The production robbing effects of these parasites has been demonstrated by the use of a controlled strategic deworming program. Weaning weight advantages of 14 to more than 20 kg have been reported in this region of the country when compared with an untreated group.2+ !%" PMID- 8484221 TI - Current and future prospects for control of ostertagiasis in northern Europe- examples from Denmark. AB - This review primarily discusses the status and prospects for control of bovine ostertagiasis in northern Europe, with examples from Denmark. There are different ongoing developments in agricultural systems and practices, and methods and possibilities for practical control depend on the intensity and specialisation of these; the modern dairy farm remains at highest risk of parasitism, owing to increasing stocking densities and limited natural control elements at hand. Epidemiology and course of infections are significantly influenced by the gradual build-up of acquired immunity, which usually contributes to prevent loss producing effects in second season and older animals. It may be of doubtful value to exaggerate worm control in first season animals, because this may reduce development of immunity with the risk of translocating parasite problems from the young to the older, economically more important age categories of animals. A number of reasons for adopting an overall consideration on worm control and performance throughout adolescence is emphasised. Control by management relies on a fairly detailed insight into local transmission factors of Ostertagia ostertagi and related trichostrongyles. No doubt future investigations will provide important additional knowledge in this area. Anthelmintics will continue to constitute a major control measure, but it is unlikely that there will be any acceleration in the rate of commercial release of new compounds. However, ongoing modifications and new formulations of existing anthelmintics will continue to be produced, and implementation at the farm level of the proper use of anthelmintics and other control measures will be one of the important tasks of the coming century. Until now, the development of anthelmintic resistance in cattle has been negligible, but it may possibly pose a potential risk over the coming decades. With regard to some new anthelmintics that have environmental concerns related to their faecal excretion, this should be carefully examined in the future. Control in the form of vaccination or biological control by microfungi or others would be attractive alternatives that should be given a high research priority. Yet, at present it is not easy to predict which of these may lead to feasible, practical control. PMID- 8484222 TI - Epidemiology of Ostertagia in the Northwestern USA. AB - The two most significant environmental factors that influence the epidemiology of Ostertagia are temperature and moisture. These factors vary more in the west and northwest than in any other part of the USA because of extreme regional differences in climate, topography, and land use. Consequently, patterns of Ostertagia transmission and inhibition also vary widely from region to region and from year to year. Recent data require revisions of previously accepted concepts of northern/southern transmission and inhibition. In particular, the flaw of liberal extrapolation of information from one region to another has now been recognized. Inhibition may not occur along the coast of the Pacific Northwest. Although not completely delineated, the transition zone between northern and southern patterns of inhibition appears to be significantly wider and more variable than previously recognized; Oregon data suggest a possible indeterminate and variable band extending north of the 45th parallel and south of the 43rd parallel. Summer inhibition has now been documented in areas of Oregon and Montana. Other than the recent Oregon and Montana studies, data on this transition zone in the Rocky Mountain region and high plains are sparse to non existent. In contrast to previously accepted doctrine, the fall rise in egg count generally exceeds the traditionally accepted spring rise in many areas. From the Pacific Northwest to the Midwest, year-round transmission patterns have been observed. The presence of geothermal ground water sources produces microclimates that favor larval survival in many areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484223 TI - Epidemiology of Ostertagia ostertagi in weaner-yearling cattle. AB - Epidemiologic events in the life cycle of Ostertagia ostertagi are best known in the weaner-yearling phase of cattle development throughout the concentrated cattle-rising areas of the world. Animal and pasture management demands placed on this age class are greater than for suckling calves and adult stock in either beef or dairy breeds. This fact alone would likely account for a higher prevalence of clinical and subclinical disease in weaner-yearlings. Additionally, the developing immune response provides relatively early protection against intestinal genera such as Cooperia and Oesophagostomum, but is delayed against Ostertagia ostertagi and Trichostrongylus axei. Both Type I and Type II disease may occur within the weaner-yearling stage. Factors affecting population changes of Ostertagia ostertagi have been described as extrinsic, i.e. weather-climate and grazing management, and intrinsic or host factors, i.e. age, sex, immune status, heredity and reproductive state. Immune status, particularly in weaner yearlings, may be of primary importance, as affected by host and extrinsic factors. With slow development of protective immunity against Ostertagia ostertagi in calves, the possible role of immunity in both induction of inhibition and larval maturation, the potential immunopathologic involvement in pathogenesis of Type II disease, hypersensitivity to larval intake in resistant adult cows, and the reported delay of a protective response following anthelmintic prophylaxis in younger cattle, the immune response may have profound influence on epidemiologic variation through age classes. Although continual epidemiological observations from birth to early adulthood in the same cattle have not been undertaken, some notable studies in the UK, the Netherlands, and Denmark have closely examined epidemiological events through first and second grazing seasons. PMID- 8484224 TI - The systematics of nematodes that cause ostertagiasis in domestic and wild ruminants in North America: an update and a key to species. AB - Studies of medium stomach worms (Subfamily Ostertagiinae) of domestic and wild ruminants in North America have refined our understanding of the systematics, host distribution and biogeography of these nematodes. Strong support for recognition of monophyly for the Ostertagiinae has resulted from preliminary phylogenetic analyses of morphological characters among these and other trichostrongylids. Evaluation of morphological and biochemical characters in our laboratory and elsewhere has not refuted the polymorphism hypothesis where paired major and minor morphotypes are postulated to represent polymorphic species within the genera Ostertagia (Ostertagia ostertagi/Ostertagia lyrata; Ostertagia leptospicularis/Ostertagia kolchida; Ostertagia gruehneri/Ostertagia arctica; Ostertagia mossi/Ostertagia dikmansi), Teladorsagia (Teladorsagia circumcincta/Teladorsagia trifurcata (= Teladorsagia davtiani), and Marshallagia (Marshallagia marshalli/Marshallagia occidentalis). The minor morphotype of Ostertagia bisonis, recognized in Eurasia (considered to be Teladorsagia kazakhstanica), has yet to be discovered in North America. The taxonomy of these species has remained stable since an earlier overview of Ostertagia spp. and Teladorsagia spp. in North American domestic stock at the 1986 Ostertagia Workshop. Investigations since 1986 have focused on comparative morphology and the clear differentiation of Ostertagiinae, primarily from wild ruminants, that have been reported or may potentially occur in domestic bovids. Among these are species which infect wild and domestic sheep (Marshallagia marshalli/Marshallagia occidentalis), bovids (Ostertagia bisonis), and cervids (Ostertagia mossi/Ostertagia dikmansi, Ostertagia leptospicularis/Ostertagia kolchida, Ostertagia gruehneri/Ostertagia arctica, Mazamastrongylus odocoilei and Mazamastrongylus pursglovei) in North America. A key is presented for identifying 15 species of the Subfamily Ostertagiinae that are parasitic in domestic and wild ruminants of North America. Four exotic species (Camelostrongylus mentulatus, Spiculopteragia spiculoptera (= Spiculopteragia boehmi), Spiculopteragia asymmetrica and Longistrongylus curvispiculum) have been reported in North America, but only in game farms and are not included in the key. Hyostrongylus rubidus, a member of the Ostertagiinae normally parasitic in pigs and only rarely reported from domestic ruminants, is not included in the keys. Additional data from comparative morphology and molecular analyses will promote a reassessment of the generic-level systematics of the Ostertagiinae and allow an evaluation of host-parasite evolution and historical biogeography. PMID- 8484225 TI - Regulation of immunity to Ostertagia ostertagi. AB - Knowledge of bovine immune response to ostertagiasis is important to understanding the mechanisms of innate and acquired immunity to this economically important helminth parasite that infects cattle worldwide. Infection causes both antibody and cellular immune responses. Evidence shows that Ostertagia possesses excretory-secretory (ES) molecules that may regulate immune cell responses that affect acquired immunity and pathophysiological changes to infection. Ostertagia can down-regulate antibody and cellular immune responses. One of these ES regulatory molecules is a lectin that causes eosinophil chemotaxis. In addition to its antigenicity, this regulatory molecule serves as a means of communication between the parasite and cells of the host immune system. It is suggested that, lacking this type of communication, Ostertagia infection may not be readily recognized by the host immune cells. A hypothesis is proposed for the mechanisms of acquired immunity to Type I ostertagiasis. Regulatory molecules of Ostertagia ES are suggested as suitable vaccine candidates. PMID- 8484226 TI - Influence of host genetics upon antibody responses against gastrointestinal nematode infections in cattle. AB - Previous studies have shown that the number of gastrointestinal nematode eggs released per gram of feces (EPG) of calves is strongly influenced by host genetics. The purpose of this study was to determine if host genetics also influenced immune recognition of parasite antigens in these same calves. Serum samples were taken at monthly intervals from calves during their first grazing season, from approximately 4 months after the onset of calving and were continued until weaning. Serum samples were analyzed for antibodies against Ostertagia ostertagi, Haemonchus placei, Cooperia oncophora, and Oesophagostomum radiatum. Significant rises in antibodies of the IgG1 class were seen against Ostertagia ostertagi, H. placei, and C. oncophora. In addition, rises in anti-Ostertagia antibodies of the IgG2 and IgM isotypes were also noted. During periods of elevated antibody responses, the sire of the individual calves was found to influence significantly the level of circulating antibody. The heritability of serum anti-parasite antibody levels was demonstrated to be between 70 and 80%, depending upon the time and antibody isotype. The antibody levels did not appear to be correlated with parasite EPG values. These results indicate that the ability of calves to recognize parasite antigens is strongly influenced by genetic factors, and that the genetic factors which control antibody responses may differ from those controlling EPG values. PMID- 8484227 TI - [The principles of aviation support for rescue-evacuation operations in eliminating the consequences of disasters]. AB - Analysing practical results of an Air Force participation in liquidation of the earthquake consequences in Armenia, 1988, and after technological catastrophe in Bashkiria, 1989, the authors substantiate the role and significance of air transportation in the system of rescue and evacuation measures, define main tasks for aviation, propose methods for calculation of required number of aircraft and its types. The data cited in this article have formed a basis for the principles of air support during rescue and evacuation procedures. PMID- 8484228 TI - [The work organization of the diagnostic module in a mobile medical-diagnostic unit]. PMID- 8484229 TI - [Skilled and specialized surgical care in the current system of medical evacuation support for the wounded]. PMID- 8484230 TI - [The experience of medical support for local wars and the problems of evacuating the wounded and sick by air]. AB - The authors disclose the constant up-grade in the role of air transportation for medical evacuation. This problem is studied on the basis of the Korean war (1951 1953), and the Afghan war (1979-1988). Thus, the average quota of wounded evacuated by air from combat areas in Afghanistan was 68.8%. In several operations it was up to 90-95%. Air transportation made it possible to shorten the time throughout the chain of evacuation and exclude some intermediate stages of evacuation. PMID- 8484231 TI - [Changes in the internal organs of wounded patients]. PMID- 8484232 TI - [Neurodystrophic disorders in mine blast trauma and the potentials for their correction]. PMID- 8484233 TI - [The organization of anesthesiological and resuscitation care under military field conditions]. AB - On the basis of the latest achievements in anesthesia and reanimation, as well as the results of special military medical exercises and documents which depict the experience of local wars, the article shows the basic features of a conception about field anesthesia and reanimation. Taking into account the experience gained in Afghanistan the author determines the principles of its organization and approaches towards the solution of important tasks assigned to anesthesiological and reanimation service in combat conditions. PMID- 8484234 TI - [The treasures of Russian medicine (the 170th anniversary of Voenno-meditsinskii zhurnal)]. PMID- 8484235 TI - [The peripheral blood indices following penetrating wounds of the chest and abdomen and their prognostic significance]. AB - Blood losses and traumatic stress provoke changes in cellular composition of blood. The greatest blood losses are more frequent in penetrating chest wounds than in penetrating abdominal injuries. A great number of wounded contract leukocytosis which is also more frequent among patients with chest wounds. The lethal cases are definitely more frequent among patients that have no leukocytosis. Immature forms of neutrophils in peripheral blood are more natural for patients with abdominal injuries. More than a half of patients had no eosinophiles in peripheral blood after having been wounded. PMID- 8484236 TI - [Complications and the proximate causes of death in typhoid]. AB - The article analyses the 65 lethal cases by typhoid in the period 1980-1986 during an outbreak of infection among the servicemen of the 40-th Army. All the deceased had the age of 18-37, 79.8% of them were 18-20 years old. The most frequent complications were: myocarditis (84.6%), pneumonia (75.4%), hemorrhagic syndrome (50.8%), intestinal perforation (49.2%), intestinal ulcer hemorrhage (21.5%), pleuritis (20.0%), purulent complications (11.7%), endotoxic shock (12.3%). The structure of proximate causes of death was as following: perforative peritonitis (30.8%), pneumonia (20.0%), acute heart failure (13.8%), intestinal ulcer hemorrhage (12.3%), suprarenal hemorrhage (7.7%). The results obtained during this study prove the fact that this outbreak of epidemic infection had the features of classical typhoid. PMID- 8484237 TI - [An epidemiological assessment of the results of laboratory research on environmental objects]. AB - On the basis of the experience in antiepidemic protection of troops several methods were worked out to make epidemiological estimation of laboratory researches which were conducted in order to disclose the risk factors that provoke infectious diseases. The main attention was focused on the problem of intestinal infections. It was stressed that the practical evaluation of fecal pollution index of water had to be done taking into account the level of infectious morbidity. In unsatisfactory indices of colimetry a threat of diseases in troops is much higher in the regions with frequent intestinal infections. In unfavourable regions with high viral intestinal infections the studies of water must be done after its purification and decontamination in order to reveal the presence of coliphages. On the basis of catering objects the article gives methods for differential estimation of the results of colon bacillus tests depending on epidemiological signification of environmental objects. PMID- 8484238 TI - [The improvement of the information activities in the system of the health and hygiene support for the troops]. AB - The system of information on health care measures in the Armed Forces of Russian Federation needs to be improved and developed. The aims and contents of record documentation must be reoriented from the tasks of uninterrupted extensive control over environmental conditions to the intensive study of health status in military units. It is desirable that the system of information support in the Ministry of Defence should be more open and accessible for other ministries and institutions occupied with environmental protection. Computer application should raise the quality of information support, restrict the number of documents inside the system, and make use of analytical and decision-making programs. PMID- 8484239 TI - [The concept of the primary prevention of diseases in servicemen]. PMID- 8484240 TI - [The occupational health problem in aviation medicine]. PMID- 8484241 TI - [The biochemical mechanisms of the decrease in work capacity in sailors exposed to high temperatures and the possible means for their pharmacological correction]. AB - The studies conducted on experimental animals and volunteers have proved that the increase of adrenalin, histamine, and serotonin ration in blood was caused by hyperthermic conditions. Activation of hormonal systems leads to acceleration of biochemical processes and to reduction of substrates in organs and tissues (such as regenerated glutathione, histidine) which are necessary for normal health status. A conclusion is made that the metabolite depletion of biochemical reactions provoke the reduction of job performance of man in the conditions of hyperthermic influence. Methods of medicamentous therapy are proposed to maintain the normal job performance of seamen in the conditions of unfavourable influence of high temperatures. PMID- 8484242 TI - [The use of current methods for analysing bacterial pyrogens in the pharmacies of treatment and prevention institutions]. PMID- 8484243 TI - [The determination of the required frequency of the represervation of technical goods for the medical service in long-term storage]. PMID- 8484244 TI - [The efficiency of the production processes in medical supply agencies studied by the network planning and management method]. PMID- 8484245 TI - Platelet concentrates in an additive solution prepared from pooled buffy coats. In vivo studies. AB - Leukocyte-depleted platelet concentrates were prepared from pools of 4 buffy coats on the day after blood collection (BC-PC). The storage medium was composed of citrate phosphate dextrose plasma and a platelet-additive solution. Autologous transfusions of 111In-labelled platelets in 9 healthy volunteers were performed on the day of preparation (day 1) and on day 5. The recovery was 54.6 +/- 8.7 (day 1) and 51.9 +/- 10.4% (day 5), T1/2 was 101 +/- 28 and 61 +/- 9 h, respectively. The survival was 8.3 +/- 1.7 and 5.7 +/- 1.0 days, respectively, using linear plot, and 7.8 +/- 2.0 and 5.8 +/- 0.5 days using the multiple hit method. In a prospective clinical study a comparison of the corrected posttransfusion increments was made between BC-PCs and apheresis-PC, and between fresh (1-2 days) and stored (3-5 days) preparations. No difference was found between BC-PCs and apheresis PCs. However, fresh BC-PCs gave higher increments than stored BC-PCs. A slight numerical difference between fresh and stored apheresis-PCs was not statistically significant. It is concluded that the BC-PC method results in platelets of equal quality to apheresis-PC. PMID- 8484246 TI - Rheological evaluation of X-ray irradiated blood. AB - CPD blood, in glass containers and polyvinyl chloride (PVC) bags, was X irradiated with 50 Gy (n = 4), and then stored for up to 4 weeks. Rheological, hematological and biochemical changes of the red cells during storage were examined. Changes in blood viscosity and various properties of red cells (deformability, shape, hematological indices and concentrations of 2,3 diphosphoglycerate and nucleotides) during storage at 4 degrees C were not altered by the irradiation. The rheological, biochemical and morphological properties of red cells were as well preserved in PVC bags as in glass containers. No abnormal and/or cross-linked proteins in red-cell membranes were induced by the irradiation. Irradiation of PVC bags did not affect the above properties of red cells through any changes in the bag constituents. In conclusion, X-ray irradiation with 50 Gy to CPD blood in PVC bags does not affect the rheological functions of red cells. PMID- 8484247 TI - Taiwan Blood Donation Program: a model for development. AB - In 1974, the Taiwan National Blood Program had not yet been fully developed. The volunteer donor base was less than 5% and there was no organized national structure or regulation of blood services. Following the founding of the Blood Donation Association and the Blood Services Foundation, promotion of an all volunteer blood program, increased utilization of blood components and the standardization of laboratory methods were strategies that led to the development of the Taiwan National Blood Program. In 1991, 1,066,082 units of blood were collected in Taiwan, serving a population of about 20 million. There are currently 6 major blood centers and 13 blood stations. Blood donation is now 100% volunteer and 78% of all blood collected is separated into 10 available components. With national organization and regulation, the transition has taken 17 years and has resulted in a community-based, all-volunteer blood supply. PMID- 8484248 TI - Production of stable human-mouse hybridomas secreting monoclonal antibodies against Rh D and c antigens. AB - Peripheral blood lymphocytes from donors immunized against Rh antigens were fused with mouse myelomas and heteromyelomas in order to obtain human-mouse hybridomas secreting antibodies specific for these antigens. Three cell lines secreting anti D IgG and two secreting anti-c IgM were stabilized and produced immunoglobulins for several months. These human monoclonal antibodies were evaluated as reagents for Rh phenotyping. Their complementary activity towards weak D and partial D antigens is examined. PMID- 8484249 TI - Antibodies to platelet glycoprotein V in polytransfused patients with haematological disease. AB - Polytransfused patients often develop platelet-reactive antibodies (PRAb). These give positive reactions in the platelet immunofluorescence test (PIFT) and may be either lymphocytotoxic (LCTAb) or platelet-specific antibodies (PSAb). The latter may be detected in the PIFT using chloroquine-treated platelets (Chl-PIFT) or by immunoblotting. Serial samples from 106 multiply transfused patients with bone marrow failure were screened by PIFT using a microplate method and flow cytometric analysis. PSAb activity was confirmed by Chl-PIFT. In 45 (42%) of the patients studied PSAb were detected; 37 (35%) formed LCTAb and 19 (51%) had co existent PSAb. Sera from 25 of 27 patients with a positive Chl-PIFT, retested by immunoblotting, recognised determinants of Mr 82-160 kD on whole platelets. A large group became sensitised to a component of Mr 105-115 kD reduced (99 kD non reduced) with similar electrophoretic mobility to GPIIIa using a monoclonal anti GPIIIa and two human polyclonal anti-HPA-1a sera; some also produced anti-GPIIb. The largest group recognised a determinant of Mr 80-83 kD, probably glycoprotein V (GPV). Three sera were immunoblotted against thrombin-treated platelets and the results confirmed GPV specificity. PMID- 8484250 TI - Molecular genetic analysis of the ABO blood group system: 3. A(X) and B(A) alleles. AB - We have employed a PCR approach to determine the nucleotide sequences of the coding region in the last two coding exons of the histo-blood group ABO genes from one A(X) and one B(A) individual. Compared with A1 alleles, the (A(X)) allele has a single nucleotide substitution (T-->A at nucleotide 646) resulting in an amino acid substitution (phenylalanine-->isoleucine at amino acid 216). Compared with B alleles, the B(A) allele has two nucleotide substitutions (T-->C at nt. 657 and A-->G at nt. 703) resulting in an amino acid substitution (serine- >glycine at aa. 235). The amino acid substitution resulting from this B(A) allele is located at the second of the four amino acid substitutions which discriminate human A and B transferases, and the amino acid residue (glycine) is identical to that of A transferase suggesting the involvement of this amino acid or its surrounding area for the recognition and/or binding of the donor nucleotide sugars. PMID- 8484251 TI - Molecular genetic analysis of the ABO blood group system: 4. Another type of O allele. AB - We have encountered an allele which seems to be another type of O allele at the human histo-blood group ABO locus. We have determined the nucleotide sequence of this allele over the coding region in the last two coding exons. This allele does not possess the single-nucleotide deletion found common among all the O alleles previously analyzed. Compared with A1 allele, this allele has three nucleotide substitutions resulting in two amino acid substitutions. The introduction of these amino acid substitutions into the A1 transferase expression construct apparently abolished the enzymatic activity of A1 transferase. PMID- 8484252 TI - Positive antiglobulin test in association with sulindac: involvement of the Rh factor. AB - We investigated the development of a positive direct antiglobulin test associated with the use of the nonsteroid anti-inflammatory drug sulindac. The drug was shown to be the cause of the positive direct antiglobulin test using red cells treated in vitro with solutions of native sulindac and its two major metabolites. Serum from the patient contained sulindac-dependent red cell antibodies which could not be demonstrated when red cells having the Rh phenotype D-- were employed in the test procedure. An eluate prepared from the patients' red cells reacted against untreated red cells having common Rh phenotypes, but not against target red cells with the Rh phenotypes D-- or Rh null. The eluate showed stronger reactivity against the cells having common Rh phenotypes when they were treated with solutions of a metabolite of sulindac, but failed to react against treated red cells having the Rh phenotype D-- or Rh null. The results of our investigations point to an interaction between sulindac and/or its metabolites and Rh structures on the red cell membrane as the initial step in the production of drug dependent and autoantibodies leading to the positive direct antiglobulin test. PMID- 8484253 TI - Severe immune haemolytic anaemia caused by intravenous immunoglobulin anti-D in the treatment of autoimmune thrombocytopenia. PMID- 8484254 TI - A new action mechanism of intravenous immunoglobulin for idiopathic thrombocytopenic purpura. PMID- 8484255 TI - Change in Fc gamma II receptor during platelet storage. PMID- 8484256 TI - HTLV-1 in multiply transfused patients in Trinidad and Tobago, West Indies. PMID- 8484257 TI - Zinc status in intensely transfused patients. PMID- 8484258 TI - Mild hemolytic disease of the newborn due to anti-Lewis(a) PMID- 8484259 TI - A cDNA clone encoding an rh polypeptide detected in RhD-negative erythroid cells. PMID- 8484260 TI - Metabolism of mephentermine and its derivatives by the microsomal fraction from male Wistar rat livers. AB - 1. The N-demethylation of mephentermine (MP), p-hydroxymephentermine (p-hydroxy MP) and N-hydroxymephentermine (N-hydroxy-MP), to produce phentermine (Ph), p hydroxyphentermine (p-hydroxy-Ph) and N-hydroxyphentermine (N-hydroxy-Ph), and the p-hydroxylation of MP and Ph, to produce p-hydroxy-MP and p-hydroxy-Ph, were examined using rat liver microsomal preparations containing NADPH. Microsomal reduction of N-hydroxy-Ph to Ph was also examined using various cofactors. In addition, enzymic system for the N-demethylation and p-hydroxylation were examined using various inhibitors. 2. N-Hydroxy-MP demethylation to N-hydroxy-Ph proceeded at a rate almost 10-fold faster than other reactions. MP demethylation to Ph, MP oxidation to P-hydroxy-MP, Ph oxidation to p-hydroxy-Ph proceeded at similar rates, whilst p-hydroxy-MP demethylation to p-hydroxy-Ph was catalysed at the slowest rate. Microsomal reduction of N-hydroxy-Ph to Ph required NADH, and the activity was similar to that of MP oxidation to p-hydroxy-MP. 3. N Demethylation of MP, p-hydroxy-MP and N-hydroxy-MP were inhibited not only by inhibitors of cytochrome P450, but also by methimazole, an inhibitor of the FAD monooxygenase system. p-Hydroxylations of MP and Ph were inhibited only by inhibitors of cytochrome P450. PMID- 8484261 TI - The metabolism of 2,3,7,8-tetrabromodibenzodioxin in the rat. AB - 1. 2,3,7,8-Tetrabromodibenzodioxin was administered to bile-duct-cannulated rats in a single oral dose. 2. The compound was metabolized in the liver and metabolites were secreted into the bile. 3. Several phenolic metabolites were identified as their methyl ether derivatives by gas chromatography-mass spectrometry after clean-up and methylation of bile samples. 4. The main metabolites were formed by aromatic hydroxylation and via displacement of Br substituents (hydrolytic debromination). 5. Trace amounts of unmetabolized TBDD were also present in the bile. PMID- 8484262 TI - Inhibition of beta-glucuronidase by natural glucuronides of kampo medicines using glucuronide of SN-38 (7-ethyl-10-hydroxycamptothecin) as a substrate. AB - 1. 7-Ethyl-10-[4-(piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), a potent anticancer agent currently under development for clinical use, is metabolized in vivo to 7-ethyl-10-hydroxycamptothecin (SN-38), which is subsequently conjugated to 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38 glucuronide). The SN-38-glucuronide was hydrolysed by beta-glucuronidase from E. coli to aglycones and glucuronic acid. 2. Four purified natural glucuronides including baicalin, wogonoside, luteolin-3'-glucuronide, and glycyrrhizin, inhibited beta-glucuronidase using SN-38-glucuronide as substrate. The inhibition potencies of these natural glucuronides toward beta-glucuronidase were similar to that of saccharic acid 1,4-lactone. 3. These results indicate that plant materials of Kampo (Japanese herbal) medicines containing these glucuronides could be used in vivo to decrease the enterohepatic circulation of SN-38 and possibly that of other drugs. PMID- 8484263 TI - Dose-dependent distribution of 3H-pentamidine following intra-tracheal administration to rats. AB - 1. The acute toxicity to the lung, and disposition, of pentamidine isethionate as a function of a pulmonary-delivered dose was investigated in the rat. 2. Acute toxicity 24 h following intra-tracheal instillation of pentamidine was determined by analysis of acellular surface protein concentration and differential cell counting of bronchoalveolar lavage fluid. These two parameters indicated that pentamidine doses > 10 mg/kg lead to increasingly severe oedematous and inflammatory responses within the lung. 3. Following intra-tracheal administration of sub-toxic doses of 3H-pentamidine (0.2-10 mg/kg), the extent of activity in liver, kidney, gut and lavage fluid at 24 h correlated significantly with dose, whereas the level of activity in lung was saturated at doses > 0.8 mg/kg. 4. Values of << 1 for liver:lung and kidney:lung ratios of 3H-activity at low pentamidine doses demonstrated the high affinity of the lung for the compound. These ratios substantially increased with pentamidine dose, reflecting distribution of the drug to liver and kidney. Association of radioactivity with these organs was rapid (< 30 min), and indicated that pentamidine is effectively absorbed from the respiratory tract following intra-tracheal instillation. PMID- 8484264 TI - Pharmacokinetics of nefiracetam and three metabolites in humans and stereoselective hydroxylation of its pyrrolidine ring. AB - 1. The kinetics of nefiracetam (I) and three metabolites (II-IV) were investigated in healthy volunteers. Compounds I-IV in serum and urine were measured by h.p.l.c. 2. After a single 200 mg dose of nefiracetam the drug was absorbed rapidly and showed peak serum levels of 16.3 +/- 0.9 nmol/ml. Cmax values of the three metabolites were comparatively low (0.96-4.89 nmol/ml), and tmax and t1/2 values of the metabolites (4.1-9.6 h and 7.8-21.9 h, respectively) were longer than those of I (1.6 h and 3.9 h respectively). Urinary excretion of I in 24 h was about 5% of the dose. The major urinary metabolite, a pyrrolidine ring scission product (IV), had a mean total excretion of 17.8% dose. The total of all four compounds in urine amounted to 43.4% dose. 3. In a multiple-dose study (daily 3 x 200 mg doses of nefiracetam for 7 days), the serum concentration profile of each compound indicated that the steady state was reached in 7 days. 4. Metabolite II existed as a racemate and III mainly as the (-)-enantiomer in human urine. PMID- 8484265 TI - Fluidity of the microsomal membrane and cytochrome P450 reduction kinetics of pig liver microsomes as a consequence of organic solvent impact. AB - 1. The effect of the aromatic solvents toluene, xylene and ethylbenzene on microsomal membrane fluidity and anaerobic NADPH-reduction kinetics were studied. 2. The relation of membrane fluidity to the kinetics of cytochrome P450 reduction by NADPH-cytochrome P450 reductase was examined with regard to a membrane mediated molecular organization of the multienzyme components of the monooxygenase system. 3. Membrane fluidity changes were detected with the steady state pyrene excimer formation method and with fluorescence lifetime measurements after incubation of the microsomes with organic solvents. 4. Increase in membrane fluidity in presence of organic solvents leads to a small but significant decrease of the rate constant of the cytochrome P450 reduction kinetics and a change in the relative amplitudes of the components of the biphasic response. 5. The results support the idea of a molecular organization of cytochrome P450 in clusters. Fluidization of the microsomal membrane by organic solvents increase the cytochrome P450 cluster formation. PMID- 8484266 TI - [Bioavailability of amino acids from several industrially-prepared protein containing products]. AB - To evaluate the bioavailability of amino acids from proteins and protein containing products, the area under the postprandial plasma-concentration-time curve of the amino acids after oral administration needs to be calculated. Therefore, basic values depending on circadian plasma concentration rhythms have to be subtracted from measured values after loading. To determine the relative bioavailability of two tested samples, e.g., a protein-containing product before and after processing or two technologically different preparations of the same protein, it is sufficient to compare their absorption-curves, both corrected by the basic values. For that purpose the mean value-curves corresponding to the group of subjects are used, because the individual courses show considerable differences, in particular due to discontinuous gastric emptying. Enzymatic hydrolysis of a lactalbumin reduces the quantitative bioavailability of the amino acids by 12%. Concerning products used in nutrition of patients and babies, the availability from ready-to-drink liquid products is about 7-10% better than that out of the same dry products in powdered form. Compared with sterilization, ultrahigh heat treatment of milk protein products improves the availability slightly, by about 1%. Processing of dried green peas destined for use in convenience food increases the protein availability by 20%. PMID- 8484267 TI - [Factors influencing the vitamin A concentration in the liver of cattle]. AB - Nineteen long-term individual- and group-feeding experiments with 180 male calves, 338 growing bulls, 302 heifers, and 344 dairy cows were carried out in order to measure the influence of feeding (straw, silages or green fodder as roughages) and different vitamin-A supplies (0-40,000 IU per 100 kg body weight per day in growing cattle or 0-120,000 IU per dairy cow per day) on liver vitamin A concentration. All together, 2,127 biopsies from livers were taken for retinol analysis. At the end of six growth experiments animals were slaughtered. Liver vitamin-A concentration of calves depends on their term at birth and is associated with the carotene intake of their mothers. The carotene content of feeds and the vitamin-A supply are the most important influencing factors on liver vitamin-A concentration of growing and lactating cattle. On the average, livers of calves fed with colostrum contained 100-200 IU, those of growing cattle fed with grass and legumes or with silages contained 200-300 or 100-200 IU resp., and those of cows fed with green fodder or silage contained 300-600 or 100-300 IU vitamin A resp. per g fresh liver. There were also values outside of the variations mentioned above. The vitamin-A storage capacity of liver and the effects of oral and parenteral vitamin-A supply to depleted calves and growing cattle were also tested. PMID- 8484268 TI - [The effect of unsaturated dietary fatty acids on the distribution of cholesterol in individual lipoprotein fractions and on serum lipids of rats]. AB - In six groups of nine young Sprague-Dawley rats each, the coconut fat used in the basal diet (group I) was replaced to 60% by pure oleic acid (group II) or linoleic acid (group III), respectively, by 0.6% of alpha-linolenic acid (IV), eicosatrienoic acid (V) and eicosapentaenoic acid (VI). A 60% replacement of the coconut fat in the basal diet by pure oleic acid, respectively, by 0.6% of eicosapentaenoic acid or eicosatrienoic acid significantly decreased the total cholesterol concentration in serum by 21% (HDL -28%; LDL -15%; VLDL -48%), respectively, 19% (HDL -12%; LDL -42%; VLDL +69%) or 15% (HDL -11%; LDL -21%) and the total free cholesterol concentration by 22% (HDL -27%), respectively, 41% (HDL -31%; LDL -66%) or 23% (HDL -21%; LDL -31%). The substitution of the coconut fat by 60% oleic acid or 0.6% alpha-linoleic acid had no influence on the total and total free cholesterol concentration in serum, though in the LDL-fraction a significant decrease of cholesterol could always be found. The concentrations of free fatty acids in serum were not influenced by the unsaturated dietary fatty acids while the phospholipid concentration was reduced by linoleic acid (-15%) and by eicosapentaenoic acid (-18%). The triglyceride content in serum was decreased by linoleic acid (-29%) and by eicosatrienoic acid (-25%). PMID- 8484269 TI - [The effect of different food forms on the urine composition and the risk of calcium oxalate stone formation]. AB - The aim of this 17-day study was to examine the influence of four different diets on urine composition and the risk of calcium oxalate stone formation in 10 healthy male subjects. In the course of phase 0, the subjects were on their individual diet for 2 days. In the following phases I, II, and III the subjects received three different standard diets for a duration of 5 days each. Whereas DIET 1 (normal mixed diet) corresponded to the dietary habits of men aged 19 to 35 years, DIET 2 (balanced mixed diet) and DIET 3 (ovo-lacto-vegetarian diet) were calculated according to the dietary recommendations of the German Society of Nutrition (DGE) for the same age-group. The risk of calcium oxalate stone formation, calculated by the computer program EQUIL of FINLAYSON, was highest on the self-selected diet and on DIET 1, but declined significantly on the intake of DIET 2 by 50% on average compared to DIET 1 and by 61% compared to phase 0. On DIET 3 no further significant decline in the risk of calcium oxalate stone formation was observed. Therefore, it can be concluded that the change of usual dietary habits into a balanced mixed diet significantly reduces the risk of calcium oxalate stone formation. With a vegetarian diet a comparable decline in urine supersaturation of calcium oxalate can be achieved with respect to a mixed diet according to requirements. Since urinary oxalic acid excretion increased significantly, a vegetarian diet is not recommend for calcium oxalate stone patients with absorptive hyperoxaluria. PMID- 8484270 TI - [Repeated perioperative administration of fructose and sorbitol in a female patient with hereditary fructose intolerance [HFI)]. AB - The present paper reports on an adult female patient whose hereditary fructose intolerance (HFI) was at first not diagnosed and who, within the space of 2 years after repeated elective surgery and the perioperative administration of fructose and sorbitol, developed "hepatic and renal failure of unclear origin." At a later stage we were able to establish the diagnosis of HFI by means of a fructose tolerance test in both she and her brother, for whom intolerance to fruit and desserts had been known since early childhood. In addition, literature references to fatalities following the parenteral application of fructose and sorbitol were analyzed. During the course of fructose infusion in both the patient and her brother with HFI, the following metabolic changes were noted: hypoglycemia, elevated rise in the blood fructose concentration, hyperlactacidemia, elevated rise in the blood fructose concentration, hyperlactacidemia, and hyperammonemia. These metabolic changes proved to be reversible after discontinuing the fructose infusion. Analysis of the literature on the fatalities following parenteral fructose administration established that fruit and dessert intolerance was known for all collated patients with HFI, and that, clearly, no regular metabolic tests had been conducted. PMID- 8484271 TI - Comparative absorption of ferrous and heme-iron with meals in normal and iron deficient subjects. AB - The relative intestinal absorption of heme- and non heme-iron in connection with a standardized test meal was studied in a group of fertile women given 16 mg Fe in the form of FeSO4 and 2 mg Fe in the form of hemoglobin. Both in normal subjects and in women with iron deficiency, the heme-iron was significantly better absorbed (16.13% +/- S.D. 8.0 vs 4.59 +/- 3.4, p < 0.01 and 22.03 +/- 8.9 vs 9.45 +/- 7.8, p < 0.05). For targeted prophylaxis of iron deficiency with small, side-effect-free doses, heme-iron is thus a valuable component which increases the absorption by about 40%. Heme-iron does not cause high concentrations in the intestinal lumen of free radical inducing, possibly harmful ferric iron. PMID- 8484272 TI - [Circadian rhythm of pregnancy contractions]. AB - Continuous measurement of normal contractions in 57 primiparae and multiparae showed a minimum in the mornings and a marked peaking of frequency between 8:30 PM and 2:00 AM. This could be due to a periodic fluctuation in the parameters influencing uterine motility. At night, motility-enhancing factors such as estrogens and prostaglandins predominate. These results suggest that in cases at high risk for premature delivery, with high pelvic scores, therapy should be continued at night. In addition, the time when the contractions were recorded should be taken into account when assessing their frequency, and the measurement repeated if necessary. PMID- 8484273 TI - [3d ultrasound in prenatal diagnosis]. AB - Three-dimensional sonography is a logical development of conventional sonography, and is a consequence of the fact that every examiner tries to imagine the three dimensional appearance of an organ on the basis of the tomographic images of it. In a long development process starting with the first 3D images in 1986/87 and lasting until today, we succeeded in developing a 3D system suitable for routine examinations, which the manufacturer is now marketing commercially. With a 3D transducer a coordinated sequence of tomograms is obtained; all the images are then computed transparently and subsequently imaged three-dimensionally as a crystalline volume. Movement of the 3D image on the computer screen is important for three-dimensional identification. The volume thus computed can then be bisected in longitudinal, transverse and horizontal planes and thus examined in real-time without any interference such as fetal movements. The horizontal sections cannot be obtained by conventional sonography. On the basis of more than 600 patients examined by this new method it was established that 3D imaging of malformations improves diagnosis and assessment, that examinations deliver accurate and reproducible results, and that section analysis can substantially facilitate diagnosis of fetal malformations. PMID- 8484274 TI - [Observations and considerations on fetal risk by umbilical cord entanglement]. AB - Mean actual pH-values in umbilical arterial (UA) and venous (UV) blood as well as mean AV-pH-differences (AVD-pH) were computed for individual Apgar-scores (1 min) in a sample of 10,580 term neonates, which were born vaginally from vertex position. The newborns of the study group showed all different kinds of cord entanglements (CE, N = 3430); neonates without CE were used as controls (N = 7144). In addition infants of the study group were attributed to two different birth weight-centile groups: < 25. and > 75. percentile. RESULTS: In the study group mean AVD-pH-values in individual Apgar-scores showed a significant (P < 10( 5)) increase when compared with controls. The numerical value of AVD-pH seems to be a function of the clinical condition of the newborn: maximum value (mean = 0.113) was reached at Apgar 7; increasing neonatal distress was accompanied by low AVD-pH-values. This phenomenon was due to a decrease of actual pH in UA-blood and an increase in UV-blood; the latter was statistically feasible (P = 0.025) only in neonates with Apgar 8. AVD-pH-values of neonates above the 75. weight centile showed a different reaction-pattern in individual Apgar-scores when compared with infants below the 25. centile: They remain constant or are slightly increased. We concluded, that blood-flow reduction in the umbilical vessels leads to a flow-dependent improvement of fetal pCO2-excretion at the placental level, which counteracts the developing metabolic fetal acidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484275 TI - [Ultrasound imaging of the symphysis fissure for evaluating damage to the symphysis in pregnancy and postpartum]. AB - In a cross-sectional study of 211 patients with a normal pregnancy the distance of the symphysis was sonographically measured during pregnancy and normal values were evaluated. Physiologically a continuous widening of the symphysis was shown up to 3 mm an average. The sonographical sign of the damage of the symphysis was a deviation in widening and also a difference in height. The value of the sonographic examination is shown in 2 cases with damage of the symphysis and compared to the x-ray picture results. PMID- 8484276 TI - [Prospective study of the clinical value of C-reactive protein in amniotic infection syndrome]. AB - In an open prospective investigation the median levels of C-reactive protein were determined in annormal collective. The median lies at 0.8 mg/dl in maternal serum withdrawn sub partu and in umbilical vein blood, and at 1.45 mg/dl immediately after ligation of the cord. Hopes on finding a biochemical parameter that could supply reliable information already during labour on a possible inflammatory infection in mother and child, did not materialize from the data found. Prediction of an infection of the newborn using CPR is only minimal. The most important practical information is given by the negative CRP in the umbilical vein blood. In this case the probability of an infection of the newborn is very slight. A high temperature during labour was the best predictor of the probability of endometritis puerperalis. This clinical finding, due to its specificity, is superior to CRP and the other parameters investigated. PMID- 8484277 TI - [The value of Doppler ultrasound studies of insulin-dependent diabetic patients]. AB - Measurement of umbilical, uterine and arcuate velocity waveforms was used to study 40 pregnancies complicated by insulin dependent diabetes. Continuous wave doppler velocimetry was used to identify flow velocity profiles during the second and third trimester of pregnancy. Resistance index (RI) was calculated to evaluate waveforms. In most of the patients with fetal growth retardation and/or pregnancy induced hypertension an increase in vessel resistance was found in uterine and arcuate arteries as well as diastolic notching. In comparison to that fact White's classification showed no significant correlation to vascular resistance determined by doppler flow measurement. This study indicates that doppler ultrasound examination may have an adjunctive role in the surveillance of pregnancies complicated by diabetes. PMID- 8484278 TI - [Obstetric-perinatal status 1990 in the Oder region (a contribution to the obstetric-perinatal care in East Brandenburg)]. AB - On the background of the first All-German-Perinatal-Study in 1992 the results in obstetrics and perinatology in the Oder-Region (east part of the State of Brandenbourg) in 1990 are described. In comparison to the results in a previous study (1985) we found a drastical decline in the number of births (newborns 1985: 10244; 1990: 7723); in addition to the changing in the reproduction- and health care behaviour, too, we have noted a decreasing perinatal mortality from 7.5% in 1985 to 4.9% in 1990. The ameliorated monitoring-rate (cardiotocography-rate) of the fetus (1985: 71%, 1990: 88.4%) and the decreasing still-birth-rate may be the main cause of this phenomenon. Clinic-births were the most common deliveries, the house-birth was the great exception; only 0.2% of all deliveries occurred at home or otherwhere. Our data support that there is no difference, except the birth rate, in relation to the situation in the "old" Federal Republic of Germany. PMID- 8484279 TI - [Patterns of cell functioning in starvation (exemplified by isolated roots)]. AB - Comparison is made over physiology of the cells of isolated roots with those of animals under long-term starvation conditions. General mechanisms of functioning of such cells are exposed. It is shown that cut-off roots could be used as proper model for the studying physiology of the cell starvation. PMID- 8484280 TI - [The biological aspects of chromatin diminution]. AB - The chromatine diminution (CD), first discovered by Boveri (1887) in ascarids, represents programmed elimination of a part of genetic material in the nuclei of the somatic cells in cyclops and ascarids, and in the protist macronuclei. The CD can be considered as a macromutation sharply changing chromosomal structure, though minimally effecting the phenotype. The analysis of CD is of significance for discussing mechanisms of origin of chromosomal organization, transformation of genome molecular structure in eucaryote evolution, role of the extra DNA. PMID- 8484281 TI - [The biomechanics of the neuroepithelium in vertebrates]. AB - Results of experiments with biomechanical interactions of neuroepithelial cells from growing brain in various vertebrate taxa are analyzed. It is shown that neuroepithelium fulfills a number of mechanical functions at the stages of blastula, gastrula, neurula, and nerve tube. The cells develop mechanical tensions differing by their form, strength and duration. Tensions and compressions are resulted from local or global changes in the form of the cells possessing mechanical sensitiveness. Regular distribution of mechanical tensions and compression is related topologically to various zones of neurons differentiations. This allows to suppose mechanical dependence of processes of determination of the nerve system development at its earlier stages. The place of biomechanical interactions in the brain formation is considered in the framework of the evolution of structural organization of the vertebrate neuroepithelium. PMID- 8484282 TI - [Current status and development of kidney transplantation]. AB - Since the first successful procedure in 1954 kidney transplantation has become a standard therapy of end stage renal disease. The knowledge of immunoregulation and immune response of the body has enabled people to recognize acute rejection of organs. HLA-testing and organ exchange on basis of HLA-compatibility are extremely important for a successful kidney transplantation. A shortage of organs is limiting the further increase of transplantations. Chronic rejection is in most cases the reason for late graft failure. Further investigations to develop new immunosuppressive drugs and to clarify immunological processes underlying chronic rejections are necessary in the future. PMID- 8484283 TI - [Dialysis treatment of chronic renal failure]. AB - Of the patients with chronic renal replacement therapy in Germany, only 27% are living with a functioning graft, while the other 73% are dialysis patients. At the end of 1990, there were about 30,000 patients on regular dialysis treatment in Germany. Without selection for chronic dialysis, the average age of newly accepted patients is 61 years. More than 30% of the new dialysis patients are diabetics. Intermittent haemodialysis (89.5%), intermittent haemofiltration (4.5%), and peritoneal dialysis (6%) are the different methods of chronic dialysis treatment in Germany. The 5-year-survival rate with regular haemodialysis treatment is 67%, for 50 years old patients without diabetic nephropathy (EDTA, Europe). PMID- 8484284 TI - [Development of colorectal tumor surgery in the last 20 years]. AB - Early and longterm results in surgery for colorectal cancer during the last two decades were investigated by a retrospective analysis of the data of 1,203 patients. During the last 10 years we registered a significant increase in more advanced tumors of the stage III and IV from 37 to 52%. Nevertheless operative mortality was reduced from 8.5 to 3.5%. The amount of curative resections was 80% constantly. The incidence of local recurrence decreased from 18 to 12%, distant metastases however were observed twice as much during the last decade (16%) as compared to the first 10 years of the observation period. Longterm survival has only slightly improved, concerning mainly stage III patients with an increase of 5-year-survival from 31 to 48%. The results of a rigorous follow up after surgery for colon and rectal carcinoma were disappointing. PMID- 8484285 TI - [Crohn disease: resection therapy over the course of two decades]. AB - Between 1972 and 1992 394 bowel resections were performed on 344 patients with Crohn's disease at the Surgical University Hospital Mannheim. The aim of this retrospective study was to examine the changes in indication, surgical technique, complication rate and mortality during this period. With the increasing incidence of Crohn's disease, the yearly number of resections has increased (from 9.8 to 30.8), while the frequency of emergency operations has declined (from 24.8% to 15.4%). During the last ten years, surgery was performed at an earlier stage; more often stenoses were resected before complications (chronic or acute intestinal obstruction, fistula and perforation) occurred. Complication rate and mortality has been reduced in the last ten years (complication rate: from 35.6% to 10.6%, mortality: from 3% to 0.7%). A significant higher complication rate was seen after emergency operations (37.1%) as compared to elective operations (12.6%) (p < 0.0001). PMID- 8484286 TI - [Laparoscopic cholecystectomy--advantages and disadvantages]. AB - From march 1990 to february 1992 we performed 600 laparoscopic cholecystectomies. In 18 cases we had to change to a laparotomy because of intraoperative problems, in 3 cases we had to laparotomise patients because of postoperative complications. 9 patients (1.5%) had a wound infection. In two prospective studies we could prove that patients after laparoscopic cholecystectomy have less pain and are in a better respiratory condition than after open cholecystectomy. PMID- 8484287 TI - [Chemoembolization of liver tumors (VX-2) using lyophilized Spherex]. AB - Chemoembolisation is a new promising approach. Until now no standardized procedures exist for the production of the embolisate-cytostatics mixture. A main technical problem when doing chemoembolisation is the proof of the complete peripheral vascular occlusion. By using lyophilized Spherex and cytostatics, diluted in x-ray contrast media, frozen pictures can be obtained and the complete proof of the embolisation is possible. Therefore the conventional x-ray examination can be used to monitor the embolisation treatment instead of the much more sophisticated DSA technique. PMID- 8484288 TI - [The importance of lectins for formation of tumor metastases and bacterial infection processes]. AB - Adhesion of bacteria and adhesion of tumor cells have much in common, especially the participation of lectins in this process. In the future it might be possible to inhibit the metastatic process into the liver (e.g. during surgical operations of malignant tumors) and bacterial adherence to mucosal linings or plastic devices by blocking of adhesion molecules (lectins) with appropriate glycoconjugates. Initial clinical trials are very promising. PMID- 8484289 TI - [Treatment principles of chronic recurrent elbow dislocation]. AB - The chronic recurrent luxation of the elbow is a seldom event. The specific diagnostic uncovers the pathomorphology of the injury. Stabilization has to be carried out according to the pattern of injury. Clinical findings and treatment are described on the basis of three observed cases. PMID- 8484290 TI - [Acute upper gastrointestinal hemorrhage caused by ruptured aneurysm of the right gastroepiploic artery]. AB - Visceral aneurysms are very rare (0.1% in autopsy-statistics). In our own review of literature we have found only 9 described cases of an aneurysm of the gastroepiploic artery. In the presented case an aneurysm was found when the patient developed an acute upper gastrointestinal bleeding. Due to the high risk of rupture (20% of all visceral aneurysms), which can be either intraperitoneally, intraluminally or into the satellite vein, the treatment should be surgically on finding. PMID- 8484291 TI - [Menetrier disease--a rare disease of the stomach]. AB - The present reports on a 51-year-old patient who presented with weight loss, anaemia, hypoalbuminaemia and ankle oedema, and was referred for laparotomy by a radiologist on the grounds of suspected carcinoma of the stomach suggested by an upper gastrointestinal x-ray series. Surgery revealed excessively thickened rugae with gyrus-like, tortuous surface epithelium folds (histologically Menetrier's disease). A gastrectomy was performed, and the patient has been symptom-free and active ever since. In addition, the author presents a review of the literature published to date describing case reports of patients with Menetrier's disease. Menetrier's disease is a benign condition of the gastric mucosa in which gastric loss of albumin has been shown to be responsible for hypoalbuminaemia. The diagnostic procedure of choice is gastroscopy because upper gastrointestinal x ray series cannot distinguish between carcinoma of the stomach with certainty. Since this is a chronic disease that does not respond to medication, treatment of choice today is (partial) gastrectomy dictated by the extent and severity of the findings. PMID- 8484292 TI - Thalamic afferents of the rat barrel cortex: a light- and electron-microscopic study using Phaseolus vulgaris leucoagglutinin as an anterograde tracer. AB - Anterograde tracers, Phaseolus vulgaris leucoagglutinin (PHA-L) and horseradish peroxidase (HRP), were used to study the thalamocortical afferents of the posteromedial barrel subfield (PMBSF) in rat primary somatosensory cortex (SI) at both light- and electron-microscopic levels. The PMBSF, also known as the barrel cortex, can be subdivided into barrel and interbarrel areas on the basis of cytoarchitectonic characteristics. Restricted injections confined to either the ventroposterior medial (VPM) or the rostral part of the posterior (Pom) nucleus allowed us to study and compare their projection patterns to the barrel cortex. We found that the interbarrel area receives inputs exclusively from the Pom, whereas the barrel area receives inputs from both the Pom and VPM. The laminar distributions of these two projections are largely segregated. After an injection of PHA-L or HRP into the VPM, labeled bouton-like swellings are found in layer VI and in layers IV through I of the barrel area, with the highest concentration in layer IV. On the other hand, after an injection of PHA-L or HRP into the Pom, labeled bouton-like swellings are distributed from upper layer V to layer I of the interbarrel area, as well as in layers V and I of the barrel area. Ultrastructural analysis showed that labeled bouton-like swellings of the VPM and the Pom pathways make synaptic contacts onto cortical neurons, and that these contacts are asymmetrical. Therefore, the VPM and the Pom projections are complementary to each other in the barrel cortex, and together they provide thalamic inputs to most layers of both the barrel and interbarrel areas. The differential patterns of terminations of the VPM and the Pom projections in the barrel cortex suggest that they may be involved in different types of cortical processing. Furthermore, our present findings may provide the anatomical basis for two parallel thalamocortical pathways, which previous physiological studies have indicated are each concerned with particular submodalities of somatic information. PMID- 8484293 TI - Finger movement deficits in the stumptail macaque following lesions of the fasciculus cuneatus. AB - Four stumptail macaques were trained to perform a key press with the index finger without associated movement of the adjacent (third) finger. Successful performance on this task required selective control over one finger (fractionation) and differential activation of muscles producing flexion or extension at different joints (multiarticulation). Following section of the fasciculus cuneatus (FC), a number of enduring deficits in finger movement capacities were observed. Over test periods of up to 2 years, fractionated key presses with the index finger could not be made, and the combination of flexion at the proximal joint with extension at the distal joints was absent. Coarticulated flexion at all the joints of each finger was substituted for the original multiarticulated, fractionated movements. We conclude that previous failures to observe impairments of finger movements following section of the dorsal columns (DCs) have resulted from the use of tasks that permit response substitution and therefore do not isolate specific movements for observation. PMID- 8484294 TI - Multidimensional scaling of painful electrocutaneous stimulation: INDSCAL dimensions, signal detection theory indices, and the McGill Pain Questionnaire. AB - Individual-differences multidimensional scaling (INDSCAL) determined the dimensions underlying ratings of electrocutaneous stimuli, which ranged from innocuous levels to individual pain intolerance at each of three frequencies. Twenty-five healthy males made pairwise similarity judgments of these 15 stimuli for the INDSCAL procedure, and then rated each stimulus on nine property scales. Signal detection theory indices, as well as ratings on the McGill Pain Questionnaire (MPQ), were also obtained. A Sensory Magnitude dimension scaled the stimuli from lowest to highest perceived intensity; this dimension was related to sensory, affective, and arousal property scales. A Frequency dimension ordered the stimuli from lowest to highest frequency; this dimension was related to the Fast-Slow property. Compared to the Frequency dimension, the Sensory Magnitude dimension was more salient to subjects who better discriminated among painful stimulus intensities, set a more stoical pain report criterion, and were less apt to endorse frequency-related MPQ descriptors. Thus, variation of physical intensity and frequency elicited complementary dimensions of subjective judgment, which were related to perceptual and attitudinal differences among individuals. PMID- 8484295 TI - Effects of baroreceptor stimulation on sensorimotor control of the hand. AB - Finger movements are presumed to be controlled by somatosensory and motor areas of neocortex via the corticospinal tract. Since baroreceptor activation appears to reduce central nervous system activity, an effect on sensorimotor control during precise manual manipulations is expected. To test this hypothesis, motor responses to slow and fast perturbations during grasping of a small object (precision grip) were examined. Baroreceptor activation was manipulated with the phase-related external suction (PRES) technique, which allows the application of baroreceptor stimulation and control conditions in a well-controlled and indiscernible way. Motor reactions following slow perturbations were influenced in the expected way in good-performance subjects. The time to stop slow perturbations was longer and the electromyographic (EMG) activity of the small thumb muscles was lower during baroreceptor stimulation than in the control condition. These effects did not appear in the fast-perturbation task. Fast perturbations were followed by EMG activity onset after about 50 msec, which indicates that a prominent part of the EMG activity must be attributed to a more automatic motor response. EMG activity following slow perturbations began after about 90 msec, and it may be assumed that these motor reactions are primarily under voluntary control. The fact that we found effects of baroreceptor stimulation in slow but not in fast perturbations could have been caused by at least partially different pathways utilized for automatic versus voluntary motor responses, which seem to be differentially vulnerable to baroreceptor activation. An electrocortical sign that precedes voluntary movements is the Bereitschaftspotential, or readiness potential. Since this potential is a slow brain potential, and baroreceptor activation is known to reduce slow brain potentials, it is plausible that baroreceptor activation primarily affects motor responses following slow but not fast perturbations. PMID- 8484296 TI - Modulation of sustained electromyographic activity by single intracortical microstimuli: comparison of two forelimb motor cortical areas of the rat. AB - In rats, a rostral and a caudal forelimb motor area (RFA and CFA, respectively) have been distinguished on the basis of intracortical microstimulation effects (see Neafsey et al., 1986, for a review). The goal of the present study was to assess and compare their relative connectional strength with target motor units of the forelimb. This was achieved by averaging modulation responses of sustained electromyographic (EMG) activity triggered by single intracortical microstimuli (S-ICMS) of relatively low intensity (mostly below 35 microA) to minimize both direct and transsynaptic current spread. In chronically prepared and ketamine sedated rats, this method produced prominent peaks and troughs in the averaged EMG at short latencies with S-ICMS currents as low as 5 microA. S-ICMS at 30-50 microA in CFA sometimes even elicited visible twitches and an EMG burst of the contralateral wrist or digits following each stimulation pulse. Increasing S-ICMS currents to about 1.5 mA revealed a sudden shortening of EMG response latencies, which was most likely induced by current spread to brainstem motor centers. S ICMS at near-threshold intensity in the majority of effective sites in both CFA and RFA produced modulation responses in more than one group of forelimb muscles, frequently also including muscles of the ipsilateral forelimb. Usually the ipsilateral responses were weaker, as were the suppression effects. Comparison of CFA and RFA revealed similar effects in terms of the number of modulated muscle groups and the response latencies. In contralateral wrist/digit muscles, facilitation responses were elicited at latencies of 9.7 +/- 1.8 msec (CFA) and 9.6 +/- 1.9 msec (RFA), with the shortest latencies around 6 msec. However, modulations by S-ICMS in RFA had significantly smaller amplitudes, had slower rates of buildup, and required higher thresholds than those obtained from S-ICMS in CFA. It is concluded, on the basis of the S-ICMS method, that both the CFA and the RFA exert a prominent and relatively direct influence on forelimb motoneurons. The present findings, together with calculations of conduction time, suggest that a contingent of corticospinal axons of the rat has oligosynaptic and possibly even monosynaptic connections with forelimb motoneurons. The recruitment of a relatively large number of muscles, including those of the ipsilateral forelimb, by S-ICMS in both areas may be explained by the prominent divergence of corticospinal axons. Further investigations are required to understand the relative positions and roles of the two areas in motor control and their possible homology with primary and nonprimary motor areas of primates. PMID- 8484297 TI - The relationship between skin compliance, age, gender, and tactile discriminative thresholds in humans. AB - Earlier research has suggested that tactile sensitivity, like visual and auditory acuity, may decrease with increasing age. But are decrements in tactile sensitivity attributable to changes in the nervous system, or simply to alterations in the mechanical properties of the skin? In the present study, skin compliance and discriminative thresholds for two-point and gap stimuli were measured on the pad of the left index finger of 102 persons ranging in age from 18 to 84 years. For both types of stimuli, age was found to be a significant predictor of tactile sensitivity, even when skin compliance and gender were controlled. The relationship between increasing age and decrements in tactile discrimination is apparently not attributable to changes in the mechanical properties of the skin, but to other factors, which may include changes in the nervous system affecting the speed, quantity, or quality of information processing. PMID- 8484298 TI - The immediate effects of peripheral denervation on inhibitory mechanisms in the somatosensory thalamus. AB - Multiunit recordings were made in the ventroposterior lateral nucleus of the thalamus in anesthetized raccoons. During recording from cells responding to cutaneous stimulation of a forepaw digit, the corresponding digit was denervated permanently (by cutting its four digital nerves) or temporarily (by injecting lidocaine into the base of the digit). Both procedures resulted in immediate increases in the inhibition that could be induced by stimulation of the adjacent digits when the original cutaneous receptive field was on the glabrous skin. In each case with temporary denervation, this enhanced off-focus inhibition decreased when the excitatory responses returned to normal. In contrast, temporary denervation of the digit during recording at sites in the hairy skin representation did not reveal this increased inhibition from adjacent digits. When capsaicin was applied to the digital nerves in two animals, the excitatory receptive fields of thalamic neurons increased in area, but were still restricted to the same part of the digit. These data indicate that the immediate unmasking of inhibitory responses, previously reported in primary somatosensory cortex of the raccoon, is also present in the thalamus. The capsaicin-induced expansion of excitatory receptive fields confirms previous experiments in other species, and suggests that C fibers play a role in modulating the size of cutaneous receptive fields. However, the enlargement of excitatory receptive fields by capsaicin is much less than the unmasking of inhibitory fields induced by digit denervation, and indicates that different mechanisms are involved in controlling these various inputs to thalamic neurons. PMID- 8484300 TI - Nursing in Texas--a personal account. PMID- 8484299 TI - Effects of dorsal root cut on the forces evoked by spinal microstimulation in the spinalized frog. AB - Spinalized frogs were microstimulated in the intermediate grey layers of the lumbar spinal cord; the forces evoked in the hindlimb were measured at several limb positions. The data were expressed as force fields. After the collection of many force fields, the dorsal roots were cut with the stimulating electrode in place, and the position-dependent stimulation-evoked forces were again measured repeatedly. We found that the position-dependent pattern of evoked forces--the force fields--did not change after the dorsal roots were cut. In other words, the postcut evoked forces pointed in the same direction as the precut evoked forces. This result was predicted and confirmed by the muscle activations (EMGs): Before and after the dorsal roots were cut, the same muscles were activated in the same proportions. In all limb positions, the rank ordering of the muscle activations remained fixed. The stimulation needed to evoke forces was increased by deafferentation, and there were subtle changes in the force magnitudes that were consistent with a linearization of the muscle stiffness by the afferents. We conclude that the microstimulation activated specific muscle synergies that resulted in limb forces pointing toward a particular posture. The patterns of evoked forces were predominantly attributable to feedforward activation of these muscle synergies. PMID- 8484301 TI - Helpful information for members considering employment outside Alberta. PMID- 8484302 TI - PARTY in Central Alberta. PMID- 8484303 TI - Needlestick injuries--cause for concern! PMID- 8484304 TI - Nursing research: an opportunity to improve. PMID- 8484306 TI - Pain corner. Analgesics: alternate routes. PMID- 8484305 TI - Breastfeeding tidbits: nipple candidiasis in the breast feeding mother. PMID- 8484307 TI - Edmonton's short stay maternity program. PMID- 8484308 TI - Cost-saving idea. PMID- 8484309 TI - On reading and writing journal articles. PMID- 8484311 TI - Holistic nursing: educational kinesiology. PMID- 8484310 TI - Taking political action. PMID- 8484312 TI - [Severe and chronic lateral sprains of the wrist with axial deviation, and their treatment]. AB - Firmly established lateral carpal instability may be practically corrected by a ligamentoplasty of the distal scaphoidal ligamentous complex. It may be entirely and definitively cured by a double ligamentoplasty of the distal scaphoidal complex and of the scapholunate ligament. Four cases with a postoperative follow up of more than 2 years are presented. PMID- 8484313 TI - The clinical use of pedobarography. AB - Several years' experience with different pedobarograph systems has demonstrated that foot pressure measurements can be used as a clinical tool. This tool can aid a surgeon's decision making, but it cannot be used diagnostically in isolation from clinical data. The clinical uses are both direct and indirect. The direct uses can be summarized as follows: to assess the effect of treatment by examination before and after a surgical procedure; to monitor progress by means of sequential measurements and to design and assess the effectiveness of orthoses. These uses are demonstrated with reference to a number of studies of normal subjects compared to patient groups using the dynamic pedobarograph. Indirect uses come from the growing body of knowledge emerging from laboratories using this equipment for research. This is helping us to understand weightbearing foot function both in health and disease. Clinicians intending to invest in the equipment can also obtain useful guidelines on the reliability of the different systems and measurements and best ways to standardize methodology. Some examples of these indirect uses are illustrated with results from studies using the dynamic pedobarograph and the EMED F system. PMID- 8484314 TI - Extensive vertebral hydatidosis. A study. AB - An exceptional case of vertebral hydatidosis with involvement of the cervical, dorsal, lumbar and sacral segments of the spine is presented. Vertebral hydatidosis is a rare form of hydatid disease. It is found in less than 2% of all cases in echinococcosis. The initial parasite localization is usually univertebral. Extensive primary lesions were related to massive infestation by tapeworm ova at multivertebral levels. At this stage, the disease presents as a malignant tumor resistant to all surgical procedures. The prognosis is poor because of severe neurological complications and inexorable spinal destruction. The hope remains that in the future an effective medical parasiticidal treatment will be available. PMID- 8484315 TI - Fracture-dislocation of the hamatometacarpal joint. A case report. AB - A case of carpometacarpal dislocation involved dorsal dislocation of the fourth and fifth metacarpal, associated with a fracture of the hamate. Reduction and Ki wire fixation resulted in good hand function. PMID- 8484316 TI - Isolated posterior dislocation of the radial head without fracture of the ulna in a child. AB - An isolated posterior dislocation of the radial head is a rare injury. We present a case report on an 11-year-old boy with a traumatic posterior radial head dislocation without fracture or bending of the ulna. The diagnosis can be difficult and should be supported with good radiographic images, since clinically the injury can be missed or misdiagnosed. PMID- 8484317 TI - Fractures of the odontoid process. Conservative and operative treatment. Prognostic factors. AB - In a retrospective study 33 fractures of the dens were analyzed. Nonoperative treatment was successful in types I and III, but unsuccessful in 48.5% of type II fractures. In addition to the poor outcome factors of Schatzker, the classification of Roy-Camille is a valuable prognostic factor. PMID- 8484318 TI - [Treatment of trochanteric fractures of the femur using the gamma nail (apropos of a series of 92 cases)]. AB - The authors treat inter- and subtrochanteric fractures with the Gamma nail. This device, which can be placed through the skin, immediately gives a stable internal fixation and offers possibilities of compression during and after surgery without any risk of head perforation. The authors discuss the results and complications of 92 operated cases reassessed after a delay of 6 to 28 months. The average age was 78 years, and 95% of the patients had been injured in home accidents. The surgical technique must be strict. Weight-bearing is complete 48 hours postoperatively, whatever the type of fracture, in 82% of the patients. Early standing postoperatively has allowed a definitive reduction in the general complications which are otherwise frequent in this type of fracture. The authors analyze the various complications they experienced during and after the surgery. Six complications during surgery have been noted and result from technical errors. These include 4 diaphyseal fractures, one case of reamer breakage and one case of drill breakage. Thirteen complications occurred after surgery: 3 diaphyseal fractures, 3 loose screws, one pseudarthrosis and 6 painful diaphyses. The authors also noted that painful diaphysis occurs when the cervical diaphysis angle of the nail is greater than 130 degrees. PMID- 8484319 TI - [Osteosynthesis of fractures of the trochanteric region using the gamma nail, apropos of 76 reviewed cases]. AB - The authors present 76 cases of trochanteric fractures, treated by a Gamma nail. The minimal follow-up was 6 months, with clinical and roentgenographical check ups. The mean age was 74 years, with a female majority as classically; the most common cause was a simple fall. Unstable fractures represented 53% of the cases, with 39% subtrochanteric; nevertheless, full weight bearing was possible in 83% of the cases. The mechanical complications of this new technique have been studied in details and compared with other most common methods of osteosyntheses: the Ender rod and the sliding screw plate. The Gamma nail shows an uncontestable superiority compared to Ender's rods, but it has little advantage to D.H.S. T.H.S., particularly because of the delay in full-weight bearing and deep infection rate. The Gamma nail moreover seems to be better adapted for the treatment of subtrochanteric fractures. PMID- 8484320 TI - The Geomedic knee prosthesis. A long-term follow-up study. AB - A retrospective long-term follow-up study of 189 Geomedic total knee arthroplasties in 143 patients was performed. One hundred and eighteen knees were replaced in patients with rheumatoid arthritis and seventy-one knees were replaced in patients with osteoarthritis. Fifty-seven knees were examined clinically with an average follow-up of 11 years. Seventy percent of these knees were painless. Lucent lines at the tibial bone-cement interface were observed in 62% of the follow-up radiographs (81 knees, mean follow-up: 10.5 years). Thirty four prostheses (18%) were removed, with loosening of the tibial component as the main cause. Retropatellar pain was not a significant problem. The 13-year survival rate was 78%, with implant removal as an endpoint. Radiographically loosened components included, the 13-year survival rate was 58%. PMID- 8484321 TI - Results of excision of calcaneal prominence. AB - Calcaneal prominence in 22 patients (37 heels) with moderate-to-severe symptoms was treated by excision after a minimum of 6 months of conservative treatment. There were 21 good, 12 fair and 4 poor results. Calcaneal exostectomy is a useful procedure in carefully selected patients. PMID- 8484322 TI - [Hospital management and short-term outcome of the severely injured: Lausanne experience]. AB - Several physiological and anatomical methods of scoring severely injured patients have been developed since the 1970s, based on very large series of patients. In this study, 59 patients are assessed by the ISS (Injury Severity Score) and the RTS (Revised Trauma Score). The mean ISS is 28, and the mean RTS is 6; the overall evolution shows a 42.4% mortality. Analysis by the TRISS method shows 12 out of 18 "unexpected" deaths, the majority of which can be explained by the fact that the ISS underestimates severe neurological trauma, and that the RTS is not consistently obtained in the early patient notes in our emergency care system. PMID- 8484323 TI - Split skin grafting of defects from fasciotomy after compartment syndrome. AB - Proper treatment of compartment syndrome is fasciotomy. Secondary skin defects often complicate the course and require skin-grafting procedures. The present investigation is a retrospective study based on 17 fasciotomies. Their courses are reported, and the possibility of primary skin excision with the purpose of delayed grafting is demonstrated. This procedure would probably reduce the number of hospital days and the number of surgical procedures. PMID- 8484324 TI - [Review of 19 cases of dislocation and fracture-dislocation of the cervical spine treated with anterior screw plates without intersomatic graft]. AB - In comparison to posterior fixation by Roy-Camille plates which does not require bone grafting, 19 cases of anterior plate fixation, also without bone grafting, are presented (11 dislocations, 2 severe sprains, 4 fracture-dislocations and 2 "tear-drop" fractures of the lower cervical spine). A satisfactory osteoligamentary consolidation was obtained in every patient. The advantages of this technique are discussed. PMID- 8484325 TI - Osteogenic sarcoma in children. A retrospective study of 58 cases. AB - Fifty-eight children between age 6 and 18 years were treated for osteogenic sarcoma in the period 1962 to 1987. Fifty-one patients with no preoperative pulmonary metastases (group A) had an overall 5-year survival rate (T5) of 41%; they were subdivided into three subgroups. In subgroup A1 treated with surgery and/or radiotherapy (15 cases), the 5-year survival rate (T5) was 33.3%, as in the classical historical series. In subgroup A2 treated with surgery and postoperative chemotherapy (19 cases) the T5 was 38.8%. In subgroup A3 treated by surgery and pre- and postoperative chemotherapy (17 cases) the T5 was 66.6%, which was statistically the best therapy (p < 0.5). This confirms the general trend in orthopedic oncology. Further data proved the negative prognostic value of male sex, while the grade of tumor and the surgical margins were important factors, but not statistically significant. Seven patients with preoperative metastases (group B) had a T5 of 0%. PMID- 8484326 TI - [Effect of a valgization osteotomy with external wedge removal on patellar height and femoro-patellar arthritis]. AB - This retrospective study assesses the effect of proximal tibial lateral closing wedge osteotomy on the patellar height and patellofemoral osteoarthritis. This osteotomy was performed on 59 knees (53 patients) for medial gonarthrosis. No cast immobilization was used. The patients presented a mean varus deformity of 9.4 degrees before surgery and a mean valgus angulation of 4.2 degrees at maximum follow-up. The theoretical effect of the osteotomy was evaluated using a geometrical model. The actual effect was evaluated using Caton's index which was measured 3 times (before the osteotomy, after one day and with a mean follow-up of 24.8 months after the osteotomy). The theoretical measure showed an increase in the patellar height. Conversely, in the patients, the measured Caton's index did not significantly increase (0.85 to 0.835) (epsilon = 0.882; risk = 5%) because of shortening of the patellar ligament. Clinical improvement in the patellofemoral compartment was noted. No radiological progression of the arthritis occurred in the patello-femoral compartment. We advocate proximal tibial lateral closing wedge osteotomy to treat femoro-tibial osteoarthritis in patients with femoropatellar osteoarthritis or with patella infera. PMID- 8484327 TI - Secondary chondrosarcoma. Four cases and review of the literature. AB - The authors present four new cases of chondrosarcoma secondary to multiple osteochondromatosis (MOC). As MOC is a familiar and hereditary condition, the patients should be evaluated throughout their lives, from childhood to adulthood. Because of the risk of malignant transformation in this condition, any adult patient complaining of pain and excessive increase in tumor size should be investigated for sarcomatous degeneration. Wide resection, when possible, must be the elected treatment in this type of patient, in order to avoid the risk of local recurrence. PMID- 8484328 TI - [Villonodular synovitis of the large joints]. AB - The authors report 11 cases of villonodular synovitis of large joints. The problems, related to diagnosis and treatment, are discussed. The results are satisfactory when a total synovectomy is performed early, before any joint damage occurs. PMID- 8484329 TI - En-bloc resection of the distal fibula for aneurysmal bone cyst. AB - A 21-year-old woman who presented with a voluminous aneurysmal bone cyst in the distal left fibula was treated with en-bloc resection. After 30 months of follow up, the stability and range of motion of the left ankle were similar to that of the contralateral ankle. PMID- 8484330 TI - [Sacrococcygeal teratoma in adults]. AB - This report describes a case of sacrococcygeal teratoma, a rare pathology belonging to the group of presacral tumors. Its clinical presentation is very variable. In this case, the tumor presented as a pilonidal cyst, which is an atypical form. The teratoma was associated with a spinal malformation, described in 25% of all cases. It was treated by "en bloc" resection with sacrectomy. PMID- 8484331 TI - A case of stenosing peroneal tendovaginitis. AB - At the foot and ankle, stenosing peroneal tendovaginitis has only rarely been described in literature. The superior and inferior peroneal retinacula, however, may cause symptoms of stenosis similar to other tendons in the foot and the hand. A case of a forty-three year-old woman is presented, where posttraumatic stenosing peroneal tendovaginitis caused sudden pain on supination of the foot. Nodular tendon swelling was present on a preoperative CT-scan. The condition was treated successfully by transsection of the peroneal retinacula. PMID- 8484332 TI - [Acute osteomyelitis of the patella]. AB - The authors report on an observation of acute osteomyelitis of the patella in a non-sickle-anemic 8-year-old child. The literature helps confirm the scarcity of the disease, the difficulties of diagnosis and the good prognosis of the lesion in the child. PMID- 8484333 TI - Cytometric analysis of testicular seminoma and spermatocytic seminoma. AB - DNA analysis of testicular seminoma (typical seminoma [TS] and anaplastic seminoma [AS]) and spermatocytic seminoma (SS) was performed to evaluate the relationship between the proliferative activity and clinical outcome, and also to determine the proliferative characteristics of SS. Nuclear DNA contents of 15 cases of TS, 17 of AS and three of SS were measured by flow cytometry. Cytofluorometric DNA analysis was performed on three cases of every tumor. All 35 cases showed aneuploidy in the flow cytometry. In comparison with TS, AS tended to have a higher percentage of G2M phase in one cell cycle, having more cell cycle numbers and containing cells of various DNA values. Many mitotic figures with larger atypical cells that characterize AS could be explained by these results. In SS, the diploid formation by the small cells and the appearance of large cells with a maximum DNA value of 40C were demonstrated. These ploidy characteristics were considered to result in the morphological expression of large, small and intermediate cells. The application of both flow cytometry and cytofluorometry to the same cases was beneficial. PMID- 8484335 TI - Pulmonary hypertension due to tumor emboli: a report of three autopsy cases with morphological correlations to radiological findings. AB - Three cases of pulmonary hypertension caused by tumor emboli to the lungs are described. Two of the three cases had a clinical diagnosis of pulmonary thromboembolism until surgical embolectomy, and the other had a diagnosis of primary pulmonary hypertension. Autopsy disclosed chondrosarcoma, choriocarcinoma and gastric cancer as the primary tumors, respectively. Pulmonary vascular obstruction due to tumor embolism leading to pulmonary hypertension is a previously rare clinical entity, and obstructed pulmonary vessels are believed to tend to be small vessels. We compared the autopsy and radiological findings and concluded that pulmonary tumor embolism involved not only the small peripheral arteries but also the segmental and/or lobar arteries. PMID- 8484334 TI - Extracranial meningioma in the parapharyngeal space. AB - A case of extracranial meningioma in the parapharyngeal space is reported. A 24 year old woman presented with swelling and tenderness of the parapharyngeal region. A tumor was palpable in this region, and the tumor was surgically removed. Macroscopically the tumor occurred from the portion between the axis and atlas. Histologically the tumor cells, which had oval nuclei and a slightly eosinophilic cytoplasm, proliferated in fibrous connective tissues to form small nests. As the cell borders were not clear, the tumor structure appeared to be syncytium-like. Immunohistochemically the tumor cells were positive for anti vimentin antibodies, anti-S-100 protein antibodies and anti-epithelial membrane antigen (EMA) antibodies in part. Electron microscopically the tumor cells had complex interdigitations of their adjacent plasma membranes. These were studded with many desmosomes. Bundles of intermediate filaments were visible in the cytoplasm. On the basis of the clinical, histological, immunohistochemical and electron microscopical features, the tumor was diagnosed as extracranial meningotheliomatous meningioma. The parapharyngeal space is an extremely rare location for extracranial meningioma, and our case is the first in Japan as far as we know. PMID- 8484336 TI - Selective zonal change of the renomedullary interstitial cells in hypokalemic rats. AB - Electron microscopic morphometry was undertaken to quantitate the morphological change of the renomedullary interstitial cells (RIC) of hypokalemic rats by using large montages. Two weeks of potassium depletion resulted in an increase of the RIC, which were restricted to the interbundle region of the inner stripe of the outer medulla. The increase of the RIC is characterized by a preferential increase in volume density (+340.0%; P < 0.01) and numerical density (+61.4%; P < 0.01) in the interbundle region but not in the vascular bundle of the inner stripe or in the inner medulla. The increased RIC in the interbundle region of the inner stripe demonstrated an increase of lipid droplets, which are known to contain prostaglandin precursors. The selective zonal change of RIC with increased lipid droplets is a characteristic lesion of hypokalemic rats and suggests an enhanced vasoactive function of RIC associated with hypokalemic nephropathy. PMID- 8484337 TI - Localization of E-cadherin adhesion molecules in human gingiva and gingival carcinoma. AB - Immunohistochemical investigations were carried out on the localization and expression of the Ca(2+)-dependent intercellular adhesion molecule E-cadherin in human gingiva and gingival carcinoma. Although E-cadherin did not appear in the parakeratinized layer of either clinically healthy or inflamed gingiva, it did appear strongly in the prickle layer and somewhat more weakly in the basal layer. Immunogold particles reactive to anti-E-cadherin monoclonal antibody in the electron microscopic findings were localized only in the vicinity of the desmosomes of the prickle and basal layers. In the case of gingival carcinoma, although E-cadherin was strongly expressed in the cells surrounding the keratinized region in the cancer nests, the expression decreased towards the marginal portion of the cancer nests. The distribution of E-cadherin in these cells may be dependent on the condition of the cancer cells that are potentially invasive. These findings suggest that cells of the parakeratinized layer of gingiva and cells of the marginal portion of the gingival carcinoma nests may easily detach or invade. In addition, the findings suggest that the gingival carcinoma used in this study tended to be invasive. PMID- 8484338 TI - Measurement of subjective phenomena in primary care research: the Visual Analogue Scale. AB - The visual analogue scale is a technique used to measure subjective phenomena. It is a self-reporting device consisting of a line of predetermined length that separates extreme boundaries of the phenomenon being measured. The purpose of this review is to report on the characteristics of the visual analogue scale technique, including its reliability, validity, accuracy, and scale value. This review presents several examples of the usefulness of the visual analogue scale technique in primary care research projects, describes its advantages and limitations, and presents suggestions for constructing visual analogue scales. PMID- 8484339 TI - Provider confidence in breast examination. AB - Many physicians have reported interest in further training in clinical breast examination, and it has been speculated that health care providers may lack confidence in their breast examination skills. At a multisite family practice residency, we surveyed a group of physicians and nurse practitioners about confidence in clinical breast examination. Forty-three percent of respondents reported impairment of the clinical breast examination by lack of confidence in skills, and 50% reported feeling only "somewhat" or "moderately" confident in their clinical breast examination skills. Residents often reported encountering few patients with breast lumps; experience with breast lumps was associated with reported confidence in the clinical breast examination. To improve and maintain breast palpation confidence and skills, residents and practicing physicians need longitudinal educational programs. PMID- 8484340 TI - Evolving colonoscopy skills in a rural family practice: the first 293 cases. AB - During the 1980s, many family physicians acquired flexible sigmoidoscopy skills for the early detection and secondary prevention of colorectal cancer. As these skills have matured, some family physicians have advanced from flexible sigmoidoscopy to the performance of colonoscopy. This is a descriptive report of this phenomenon from the private practice of one family physician. The first five years of total colonoscopy experience (293 procedures) were analyzed. No complications were encountered. A learning effect (measured in terms of scope depth and anatomical depth) was present during the first 50 procedures; an improvement in examination depth between the 25th and 50th procedure was present. Previous abdominal surgery had an effect on limiting scope-insertion depths. There were no complications, and among sedated patients, 137/253 (54%) of procedures reached the cecum. Important findings included cancer, polyps, and colitis. Twenty-seven percent (9/34) of important pathological findings were located beyond the reach of the 60 cm sigmoidoscope. This study of full colonoscopy in private family practice suggests it is safe, and the diagnostic yield is substantial. Additional studies by family physicians are needed regarding technique, quality assurance, and patient satisfaction. PMID- 8484341 TI - Diabetic limb infections: identification of microorganisms and selection of treatment. AB - Polymicrobial lower limb infections are common complications among diabetic patients, yet their antimicrobial management remains mostly empiric. A retrospective study of the clinical circumstances of 74 patients accounting for 101 hospital admissions was performed. Risks for vascular disease, clinical and microbiologic evidence for infection, as well as antimicrobial drug selection in these patients, were compiled. Culture materials were obtained from either swab or incision and drainage techniques in 65 (64.4%) patients. Eighty-two (81.2%) patients received antimicrobial therapies. Of the 172 antimicrobial agents prescribed, cephalosporins were utilized 83 times. Twenty-nine (28.7%) patients received amputations. Average total hospital charges were $7,368 per hospital stay, $485 per day. PMID- 8484342 TI - Public perceptions of radon risk. AB - Since 1984, a significant amount of media attention has focused on health threats from radon gas exposure. Using a probability telephone survey of adults (n = 685), we studied public perceptions of risk from radon exposure versus other environmental health risks. The results indicated that 92% of those individuals who had heard of radon believe radon to be a health risk, although only 4% believe they are currently exposed to high levels of radon gas. Perception of risk from radon was positively related to other perceptions of environmental risks. Younger and less educated individuals were more likely to perceive radon as a health risk. Women were three-and-one-half times as likely as men to perceive risk from radon. However, there was no significant relationship between perceived risk from radon and cigarette smoking. Media attention has apparently led to public awareness of radon hazards, but further attention is needed to improve smokers' awareness of their special risks from radon. PMID- 8484343 TI - Family practice research in Spain. PMID- 8484344 TI - A pilot study of white-coat and labile hypertension: associations with diagnoses of psychosocial dysfunction. AB - Variable blood pressure responses, manifesting either as a "white-coat" phenomenon or lability between office visits, confound hypertension management decisions. An attempt was made to determine whether these phenomena are associated with concurrent diagnoses of psychosocial dysfunction, therefore mitigating against antihypertensive medical therapy. Forty-seven patients with such variable blood pressure responses were identified in a rural family practice over a three-year period and compared to randomly selected age- and sex-matched controls for the following concurrent diagnoses: generalized anxiety, psychogenic spastic bladder, panic disorder, depression, alcohol use, chronic headache, fibromyalgia, temporomandibular joint syndrome, irritable bowel syndrome, and premenstrual syndrome. No statistical associations between white-coat hypertension and these diagnoses were demonstrated although a small sample size tempers conclusions. However, chi-square analysis (P < 0.01) of the phenomenon characterized by lability of blood pressure between different office visits demonstrated a statistical association with alcoholic hepatitis in men. White coat hypertension is a diagnosis that may warrant disassociation from other psychosocial disorders, although further study is indicated. Physicians should remain attuned to the presence of lability of blood pressure in males and consider possible associations with alcoholism. PMID- 8484345 TI - Differentiation of physical and psychological fatigue. AB - Although chronic fatigue is a common complaint in family practice, little research has focused upon differentiating physical causes from psychological causes based upon historical information. This pilot study was conducted to determine whether psychological and fatigue scales could be used to identify potential causes, and to assess the utility of using fatigue characteristics to distinguish psychological from physical fatigue. Family health center patients were randomly selected and interviewed for the presence of fatigue. Those with significant fatigue were asked to participate in a structured, in-depth interview concerning fatigue characteristics, psychiatric conditions, and symptom checklists. Of 248 patients interviewed, 17 (6.9%) had fatigue. Fourteen patients had at least one psychiatric disorder. Fatigue severity correlated with depression severity in depressed patients (r = 0.83, p < 0.02) and with severity of phobic anxiety (r = 0.55, p < 0.1) in panic attack patients. However, fatigue characteristics generally did not differentiate between those with and without associated psychological disorders. PMID- 8484346 TI - Whole language. PMID- 8484347 TI - Constraints on communication in classrooms for the deaf. AB - One explanation for the relatively low scholastic achievement of deaf students is the character of communication in the classroom. Unlike aural communication methods, line-of-sight methods share the limitation that the receiver of the message must look at the sender. To assess the magnitude of this constraint, we measured the amount of time signers were looked at by potential receivers in typical secondary school classes for the deaf. Videotaped segments indicated that on average the messages sent by teachers and students were seen less than half the time. Students frequently engaged in collateral conversations. The constraints of line-of-sight communication are profound and should be addressed by teaching techniques, classroom layout, and possibly, the use of computer communication technology. PMID- 8484348 TI - Social support, motivation, language, and interaction. A longitudinal study of mothers and deaf infants. AB - This project examined the effect of early cognitive, social, and communicative experiences on later social and language development in deaf infants with hearing mothers. Interactions between mothers and deaf infants were found to be positively influenced by social support provided to mothers in the early months of the infants' lives, mothers' visual and tactile responsiveness when their infants were 9 months of age, infants' ability to cope with interactive stress at 9 months of age, and fewer attempts by infants to engage with the social environment during the mastery motivation assessment at 9 months of age. Neither mother-infant affective matching nor maternal visual-tactile responsiveness correlated with the deaf infants' language level. PMID- 8484349 TI - Accessibility of mental health services and crisis intervention to the deaf. AB - The percentage of deaf and hard of hearing people who need mental health services and crisis intervention is similar to that of the general population. Hence, a survey was conducted to evaluate the accessibility of these services to the deaf population in Rhode Island. Staff members at agencies were asked about the number of deaf clients they serve, and asked to judge the accessibility of their basic services (e.g., TDD, interpreters). The results indicated that although more than 70% of respondents indicated they had served deaf people during the past year, only 25% provided certified interpreters and only 39% were accessible to the deaf community via TDD. Other services as well as the needs of the deaf community are also discussed. PMID- 8484350 TI - Deaf and hard of hearing adolescents' memory for concrete and abstract prose. Effects of relational and distinctive information. AB - In two experiments, we examined deaf and hard of hearing adolescents' memory for prose as compared to that of hearing students. The study focused on the possibility that deaf and hard of hearing readers might make relatively less use of relational information in textual materials. Text structure and material concreteness were manipulated, and memory for relational and distinctive information was assessed. Results indicated that deaf and hard of hearing students remembered the abstract materials as well as they did the concrete materials. They were less likely than hearing students to remember idea units (concrete or abstract) holistically within passages, but they showed relatively better memory for individual words. This difference disappeared when the same sentences were presented without global paragraph coherence. The findings suggest that deaf and hard of hearing readers may be less likely than hearing readers to integrate text information across idea units, although they may retain as much information from within units. PMID- 8484351 TI - Perceptions of the oldest hearing child of deaf parents. On interpreting, communication, feelings, and role reversal. AB - Sixteen hearing children of deaf parents were matched with sixteen hearing children of hearing parents on age, school grade, sex, parent education level, and socioeconomic status. All children in the study were the oldest in the family. The children completed a questionnaire and a structured interview. Both the questionnaire and the interview investigated the issues of feelings toward parents, communication with parents, interpreting, and role reversal. The results indicated no significant difference between the two groups on the feelings, communication, and role-reversal scales. A significant difference was found between the groups on the interpreting scale as well as on the responses to the interview situations. The ages of the children and the degrees to which the parents relied on them to interpret appeared to have a strong influence on the children's feelings toward parents, communication with parents, and views on role reversal. PMID- 8484352 TI - The use of speech-based recoding in reading by prelingually deaf children. AB - We evaluated the extent to which prelingually deaf school children who were educated orally made functional use of speech-based codes in reading processes. The study involved two experimental reading tasks: (1) memorizing written words in association with meaning and (2) serial order recall of written word strings. The subjects were 78 school children 6 to 13 years of age. The results revealed a developmental change in the use of coding strategies: up to 9 years of age, most children seem to process written words by means of visual codes; older children tend to differentiate and appear to prefer either a visual or a speech-based strategy. The latter was found to be associated with better performance in reading tasks. PMID- 8484353 TI - Improvements in the English syntax of deaf college students. AB - The present study was designed to determine whether prelingually deaf students continue to improve in their knowledge of English syntax once they reach the college level. Students were assessed on their knowledge of nine English structures at the beginning and the end of the academic year. The results revealed significant improvement on all structures; however, students with lower general English proficiency improved to a significantly greater extent than students with higher general English proficiency. This suggests that deaf students with low proficiency might benefit from an increase in explicit grammar instruction. The results of this study are promising in that improved English syntax provides deaf students with more degree options and greater access to college-level reading materials. PMID- 8484354 TI - Dextropropoxyphene addiction--a drug of primary abuse. AB - In order to establish a profile of the abuser of dextropropoxyphene (DPX) in our community, we reviewed all the records from the Detoxification Unit in the Mental Health Institute in Mexicali, Baja California, Mexico. A total of 209 records were reviewed, and 73 were included in our study. Those included had a diagnosis of DPX dependence according to DSM-III-R and no associated psychiatric pathology. Most of them were single, unemployed males, with a history of at least 4 years of continuous DPX abuse. They were consuming an average dose per day 3.5 times higher than the maximum therapeutic dose recommended. The onset of generalized seizures associated with the DPX abuse was confirmed in 53% of the cases. The drug most frequently abused along with DPX was a benzodiazepine (p < .01), followed by marijuana, heroin, alcohol, stimulants (cocaine and amphetamines), and inhalants; 17% of the cases were pure DPX abusers. DPX was the first opiate ever abused in 67% of the cases, 19% had abused heroin before DPX, and 14% started the use of both at the same time. The difference among these groups (p < .01) suggests DPX as an opiate of primary abuse and not as secondary to heroin dependence. PMID- 8484355 TI - Cocaine in the hair of mother-infant pairs: quantitative analysis and correlations with urine measures and self-report. AB - A sample of mothers who had used crack cocaine while pregnant was evaluated during the postpartum period before random assignment to drug treatment. Mean infant age was 74 days. Paired hair samples were acquired from 63 mothers and 63 infants. Maternal urine was screened for cocaine and benzoylecgonine; three different drug use self-report measures were also collected. Normalizing transformations of all hair and urine data preceded analyses. The initial correlation of mother and infant hair (r = .41, N = 62, P = .001) was strengthened (r = .62, N = 30, P < .0005) by removing from the dataset maternal hair independently judged to be damaged. Damage to hair is associated with certain types of "hair care" products. The damaged maternal hair bore no quantitative relationship to infant hair (r = -.04, N = 30, P = .41). Poor quality hair samples could have been partly anticipated because self-reported use of hair products had a significant contingent relationship to laboratory-judged damage to hair (Z kappa = 2.28, P = .01). Maternal urine benzoylecgonine correlated with maternal hair (r = .41, N = 60, P = .001) and, of course, with maternal urine cocaine (r = .63, N = 60, P < .0005). None of the three self report measures (use in past 30 days, duration since first use, average regular use) significantly correlated with any of the hair or urine measures. Factor analysis of drug use variables identified three factors possibly representing long-term use, recent use, and some artifact of self-report. In summary, hair analysis may provide a quantitative index of exposure when the hair is not damaged. The amount of self-reported drug use could not be corroborated with analytic measures of hair or urine. Studies in which self-reported cocaine use is a scalar variable should be interpreted cautiously. PMID- 8484356 TI - Comorbidity in pregnant patients in a psychiatric inpatient setting. AB - The impact of substance abuse on mental illness is substantial. The consequences of comorbidity on pregnant women has not been previously reviewed. This paper discusses the implications of interrelationship of substance use and mental illness on pregnancy. We present data from a retrospective study of pregnant women admitted for psychiatric care, reviewing the relationships of comorbidity to their demographic, psychiatric, and obstetrical histories and follow-up prenatal care. PMID- 8484357 TI - Cigarette smoking and methadone dose levels. AB - Cigarette smoking has been shown to increase consequent to the acute administration of methadone. This suggests the possibility that differences in maintenance dose levels might be associated with differential smoking rates. It is of special concern that higher maintenance levels of methadone may lead to more cigarette smoking because of the putative beneficial effects of higher doses on illicit drug use, treatment retention, and the like. Two experiments were conducted to test the hypothesis that higher maintenance doses of methadone are related to more cigarette smoking. Smoking was measured by self-report and expired carbon monoxide, and the amounts were correlated with subjects' methadone dose levels. The results showed smoking rates of 85% and that self-reported smoking significantly correlated (r = -.52) with CO. Maintenance doses, however, were not correlated with smoking levels. This suggests that the acute effects of methadone on smoking are nullified as clients habituate to dose level, and that decisions regarding appropriate methadone dosage can be made on other grounds. PMID- 8484358 TI - Alcohol and heroin use patterns of narcotics addicts: gender and ethnic differences. AB - Data on lifetime alcohol and heroin use by 443 White and Chicano addicts of both genders were obtained from a sample of admissions to several Southern California methadone maintenance programs. Patterns of alcohol and heroin use were examined with respect to gender and ethnic differences. Repeated-measures MANOVA established an inverse pattern of alcohol and heroin use for all four groups, confirming and extending the findings of a previous study by the authors. With this additional evidence, the authors propose a compensatory model that explains the obtained inverse pattern of alcohol and heroin use and that may be suitable in examining concurrent or sequential use of other psychoactive substances in addition to alcohol. Significantly higher levels of heavy alcohol use were reported by Chicano than by White addicts. Overall findings indicate that after heroin addiction occurs, there is a convergence in patterns of substance use by both genders, although variations related to ethnicity persist, particularly for alcohol use. PMID- 8484359 TI - Attrition from an evening alcohol rehabilitation program. AB - In recent years many groups have become interested in the potential cost savings and efficacy of outpatient treatment for chemical dependency. This study was originally conceived to answer questions of both patients and staff concerning graduation and attrition rates in an evening outpatient alcohol treatment program. Of particular interest were gender effects, rates of attrition across two progressive program levels, and whether alcohol-only users and self-initiated clients fared better in treatment than did polysubstance users and patients who were referred by others. Medical records were available for 103 of the 107 treated patients, and of these, 27 remained in the program until graduation. Women were more likely to graduate and remain in the program longer than men. Alcohol users were more likely to graduate than subjects with additional substance use disorders. Graduation rates did not differ significantly between contact initiators and noninitiators; however, the former dropped out of treatment more quickly. The study is an example of the potential use of data obtained from an existing agency data base. PMID- 8484360 TI - Air pollution and respiratory morbidity among adults in southern California. AB - This paper reports the results of an investigation of the acute effects of air pollution in 321 nonsmoking adults residing in Southern California. Previous epidemiologic investigations of effects of acute exposure to ozone have focused on groups who may not be representative of the general public, such as asthmatics or student nurses. For this study, participants recorded the daily incidence of several respiratory symptoms over a 6-month period between 1978 and 1979. The authors examined the impact of ambient concentrations of ozone, particulate sulfates, and other air pollutants on the incidence of respiratory morbidity, measured as either upper or lower respiratory tract symptoms. Using a logistic regression model, the authors found a significant association between the incidence of lower respiratory tract symptoms and 1-hour daily maximum ozone levels (odds ratio (OR) = 1.22, 95% confidence interval (Cl) 1.11-1.34, for a 10 parts per hundred million (pphm) change), 7-hour average ozone levels (OR = 1.32, 95% Cl 1.14-1.52), and ambient sulfates (OR = 1.30, 95% Cl 1.09-1.54, for a 10 micrograms/m3 change), but no association was found with coefficient of haze, a more general measure of particulates. The existence of a gas stove in the home was also associated with lower respiratory tract symptoms (OR = 1.23, 95% Cl 1.03 1.47). The effects of ozone were greater in the subpopulation without a residential air conditioner. In addition, ozone appears to have had a greater effect among individuals with a preexisting respiratory infection. PMID- 8484361 TI - Air pollution and emergency room admissions for chronic obstructive pulmonary disease: a 5-year study. AB - An association between sulfur dioxide levels in urban air and the daily number of emergency room admissions for chronic obstructive pulmonary disease was previously reported in Barcelona, Spain, for the period 1985-1986. The present study assesses this association over a longer period of time, 1985-1989. This made it possible to carry out separate analyses for the winter and summer seasons and thus to control more adequately for weather and influenza epidemics. An increase of 25 micrograms/m3 in sulfur dioxide (24-hour average) produced adjusted changes of 6% and 9% in emergency room admissions for chronic obstructive pulmonary disease during winter and summer, respectively. For black smoke, a similar change was found during winter, although the change was smaller in summer. The association of each pollutant with chronic obstructive pulmonary disease admissions remained significant after control for the other pollutant. The present findings support the conclusion that current levels of sulfur dioxide and black smoke may have an effect on the respiratory health of susceptible persons. PMID- 8484362 TI - Ethnic differences in risk factors associated with the prevalence of non-insulin dependent diabetes mellitus. The San Luis Valley Diabetes Study. AB - Non-insulin-dependent diabetes mellitus is 2-5 times more common in Hispanics than in non-Hispanic whites in the United States. The authors conducted this case control study in two Colorado counties from 1984 to 1986 to determine whether known risk factors for non-insulin-dependent diabetes mellitus explained the excess incidence in Hispanics. There were 279 subjects with prevalent diabetes and 488 subjects with normal glucose tolerance who were eligible for this analysis. After adjustment for age and sex, results showed that Hispanics were 3.5 times more likely than non-Hispanic whites to have non-insulin-dependent diabetes mellitus (95% confidence interval 2.4-4.9). The excess risks of diabetes associated with body mass index, subscapular and triceps skinfold thickness, family history of diabetes, and income were similar in Hispanics and non-Hispanic whites, after adjustment for age and sex. However, 1-unit increases in subscapular/triceps skinfold ratio and waist/hip ratio were associated with greater increases in risk among non-Hispanic whites than among Hispanics. When risk factors were entered into logistic regression models simultaneously, higher subscapular skinfolds, a higher waist/hip ratio, family history of diabetes, older age, male sex, and lower income were independently associated with non insulin-dependent diabetes mellitus in both ethnic groups. No association was found with skin reflectance, a marker for Amerindian admixture. While the excess risk of diabetes in Hispanics was reduced, a significant 1.9-fold excess risk in Hispanics remained. Further studies are needed to understand factors contributing to the excess prevalence of diabetes in Hispanic Americans. PMID- 8484363 TI - Effect of multiple risk factors on differences between blacks and whites in the prevalence of non-insulin-dependent diabetes mellitus in the United States. AB - The higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in US blacks as compared with whites may be due to a higher frequency of NIDDM risk factors in blacks, a higher inherent susceptibility to NIDDM among blacks, or the risk factors' having a greater effect in blacks. The authors evaluated 4,379 subjects from the Second National Health and Nutrition Examination Survey (1976 1980) for whom NIDDM was ascertained by medical history and oral glucose tolerance test, and for whom data on a number of risk factors were available. The prevalence of NIDDM was 60% higher in blacks than in whites (p < 0.001) and was highest in black women. Although most risk factors for NIDDM were more common in blacks, this higher frequency did not completely explain the racial disparity in the prevalence of NIDDM. After adjustment for all risk factors by logistic regression, an elevated risk of NIDDM was particularly evident at higher obesity levels in blacks as compared with whites; the odds were 70% higher for blacks at a percentage of desirable weight of 150 (95% confidence interval 1.1-2.8). The risk of NIDDM associated with obesity was greatest in black women: The odds in this group were sevenfold higher at a percentage of desirable weight of 150 versus 100 (95% confidence interval 2.6-18.8). The possibility of racial differences in metabolic adaptation to obesity highlights the importance of preventing this condition in blacks, particularly in black women. PMID- 8484364 TI - Invited commentary: do risk factors explain ethnic differences in type II diabetes? PMID- 8484365 TI - Heart rate, physical activity, and mortality from cancer and other noncardiovascular diseases. AB - The relations between resting heart rate on electrocardiogram, usual physical activity, and risks of all noncardiovascular mortality, cancer mortality, and other noncardiovascular mortality were examined in 7,735 middle-aged British men drawn from general practices in 24 British towns. Subjects were examined and administered questionnaires in 1978-1980. During a follow-up period of 9.5 years (to December 1989), there were 334 deaths from noncardiovascular causes, including 225 cancer deaths. A strong positive association was seen between heart rate and all noncardiovascular mortality, cancer mortality, and other noncardiovascular mortality, even after adjustment for age, blood cholesterol, body mass index, heavy alcohol drinking, physical activity, preexisting ischemic heart disease, smoking, social class, and systolic blood pressure (p < 0.01). The relative risks in men with heart rates of > or = 90 beats/minute, in comparison with those with heart rates of < 60 beats/minute, were 2.33 (95% confidence interval (CI) 1.42-3.74) for total noncardiovascular mortality, 1.68 (95% CI 0.92 3.10) for cancer mortality, and 3.56 (95% CI 1.65-7.65) for mortality due to other noncardiovascular causes. The positive associations with cancer and all noncardiovascular mortality persisted even after further adjustment for lung function (forced expiratory volume in 1 second) and exclusion of men with underlying ill health and of deaths occurring within the first 5 years of follow up. A significant inverse association with seen between physical activity and risk of cancer death, even after adjustment for the above factors and heart rate, with a significant reduction only in those engaged in high levels of usual physical activity (relative risk = 0.62, 95% CI 0.39-0.98). The data suggest that in middle-aged men, resting heart rate and physical activity are independent prognostic factors for cancer mortality. PMID- 8484366 TI - Risk factors for idiopathic rhegmatogenous retinal detachment. The Eye Disease Case-Control Study Group. AB - The objective of this case-control study of idiopathic retinal detachment was to evaluate previously suggested hypotheses about risk factors for retinal detachment and to investigate whether new ocular or systemic risk factors could be identified. Between 1986 and 1990, data were obtained at five US clinical centers on 253 patients with idiopathic retinal detachment and 1,138 controls. Patients with pathologic myopia were excluded. Data were collected from interviews, clinical examinations, and laboratory analyses of blood samples. Only one clearly relevant risk factor, myopia, emerged from the analyses. An eye with a spherical equivalent refractive error of -1 to -3 diopters had a fourfold increased risk of retinal detachment compared with a nonmyopic eye; if the refractive error was greater than -3 diopters, the risk was increased 10-fold. The data suggest that almost 55% of nontraumatic detachments in eyes without previous surgery are attributable to myopia. The etiology of retinal detachment appears to be related to the architecture of the eye. The study found no evidence that systemic factors, particularly cardiovascular factors, play a role. PMID- 8484367 TI - Validation of 1989 Tennessee birth certificates using maternal and newborn hospital records. AB - In 1989, the state of Tennessee adopted a new birth certificate which incorporates changes recommended by the National Center for Health Statistics in the revised US Standard Certificate of Live Birth. The data now being collected are intended to provide improved information for understanding maternal and infant health issues. To assess data quality, the authors compared information reported on the 1989 Tennessee birth certificates with the same data obtained from an ongoing case-control study in which the delivery hospital medical records of mothers and infants were reviewed by trained nurse abstractors using a structured data collection instrument. Cases (n = 1,016) were all infants born in Tennessee in 1989 with birth weights less than 1,500 g or other infants who died during the first 28 days of life. The infants were identified from linked birth death certificate files. Control infants (n = 634) were randomly selected from the noncase population. The most reliable information obtained from birth certificates was descriptive demographic data and birth weight. The quality of information obtained from the new birth certificate checkboxes varied. Routine medical procedures were better reported on the birth certificates than relatively uncommon conditions and occurrences, even serious ones. Caution is needed in using birth certificate data for assessment of maternal medical risk factors, complications of labor and delivery, abnormal conditions of the newborn, and congenital anomalies, since sensitivity is low. PMID- 8484368 TI - How safe were today's older drivers when they were younger? AB - Data from the Fatal Accident Reporting System for 1975-1990 were used to perform longitudinal analyses of car driver fatality rates (driver fatalities per million population) for a 16-year period; for example, the fatality rate of drivers born in 1960 was examined for ages 15 years through 30 years. It was found that fatality rates for male drivers of a given age systematically decline with increasing birth year; for example, 20-year-olds born in 1970 have lower fatality rates than do 20-year-olds born in 1960. The fatality rates for cohorts of drivers of either sex do not begin to increase appreciably until about age 70 years, and then they approximately double by age 80 years. These increases are of a lesser magnitude, and occur later, than those found in the earlier cross sectional analyses that identified the "older driver problem." PMID- 8484369 TI - Estimating the variance of standardized rates of recurrent events, with application to hospitalizations among the elderly in New England. AB - Usual approaches for estimating the variance of a standardized rate may not be applicable to rates of recurrent events. Where individuals are prone to repeated health events, Greenwood and Yule (J R Stat Soc [A], 1920;83:255-79) advocated use of the negative binomial distribution to account for departures from the assumption of randomness of recurrent events required by the Poisson distribution. In this paper, the authors implemented the negative binomial distribution in the computation of annual hospitalization rates within certain hospital market areas. Data used were from 1,549,915 New England residents aged 65 years or more who were enrolled in Medicare between October 1, 1988, and September 30, 1989, and who had 458,593 hospital admissions during that year. New England was partitioned into 170 hospital market areas ranging in population size from 162 to 70,821 elderly Medicare enrollees. The negative binomial distribution demonstrated substantially better fits than the Poisson distribution to the numbers of hospitalizations within hospital market areas. Estimated standard errors for indirectly standardized rates based on the negative binomial distribution were 25-51 percent higher than estimated standard errors that assumed an underlying Poisson distribution. Using regression analysis to smooth overdispersion parameters across hospital market areas produced similar results. The approach described in this paper may be useful in estimation of confidence intervals for standardized rates of recurrent events when these events do not recur randomly. PMID- 8484370 TI - Sample sizes for prevention trials have been too small. AB - Planners of several large prevention trials have overestimated the expected incidence of events in the control group, largely because they failed either to recognize or to adequately correct for various effects of population selection. Consequently, the studies have been too small in size or too short in duration to achieve their stated objectives. The selection effects include those engendered by the choice of the target population, the self-selection of volunteers, and protocol exclusions. This paper presents a taxonomy of these effects and the likely direction of their influence on the incidence of events and on mortality rates from other causes. Little information is available to help sample-size planners in adjusting for these effects. A few studies have provided information on the extent to which control group incidence rates have fallen short of expectations. In particular, researchers from the University of Minnesota's Colon Cancer Control Study have provided a detailed comparison of event incidence and all-cause mortality rates with general population rates. (AM J Epidemiol 1993;137:797-810). Other studies should publish similarly detailed information to assist sample-size planners of prevention trials. Until more information is published, this paper provides preliminary guidelines for prevention trial sample size planning. PMID- 8484371 TI - Estimating the duration of ongoing prevention trials. AB - The authors present a method of estimating the duration of ongoing prevention trials, showing how the method was applied to the Colon Cancer Control Study, a University of Minnesota study of occult blood testing undertaken to screen for colorectal cancer in older Minnesotans. In that study, begun in 1975 and ongoing, as in several other recent large prevention trials, it was necessary, after the start of the study, to revise upward the initial estimates of study duration derived from general population experience. The underestimates arose because the planners had not adequately taken various population selection factors into account in estimating the expected number of events in the control group. In this paper, the authors outline a method for estimating control group event rates and study duration requirements (and, in some circumstances, also sample size requirements) of prevention studies, via models of disease-specific and all-cause standardized mortality ratios which adjust for various selection effects. The authors also validate the model for disease-specific standardized mortality ratios by means of independent estimates of disease incidence and case survival. PMID- 8484372 TI - Re: "Total energy intake: implications for epidemiologic analyses". PMID- 8484373 TI - Comparative epidemiology of Down syndrome in two United States population, 1970 1989. AB - This study compared the epidemiology of Down syndrome over a 20-year period, 1970 1989, in two populations in which livebirths with Down syndrome were believed to be highly ascertained. One population was a 10-county region in southwest Ohio; the second was a five-county region in metropolitan Atlanta, Georgia. The major objectives were to 1) compare observed incidences of Down syndrome over the entire study period; 2) calculate expected incidences of Down syndrome for each population and compare these with observed incidences; 3) determine incidence trends throughout the period; and 4) examine the impact of prenatal diagnosis on the observed incidence of Down syndrome in each population. Excluding aborted fetuses with Down syndrome diagnosed prenatally, the observed incidence of Down syndrome, 0.98, was significantly lower than that expected, 1.27, within the Atlanta white data set. Once the observed data were adjusted to include aborted fetuses with Down syndrome (total incidence = 1.17), no statistically significant differences remained. No differences were found between observed and expected incidences of Down syndrome for whites in southwest Ohio or for other races in either population. Although uncorrected observed incidences were significantly different between the two populations of whites for the entire 20-year period, the differences again disappeared after the data were corrected to include aborted fetuses. No significant effect of prenatal diagnosis on those of other races was found in either population. Expected Down syndrome incidences rose from the late 1970s throughout the 1980s for both racial groups in Ohio and Atlanta, Georgia; however, because the termination of fetuses with Down syndrome increased over the decade, the observed incidence among whites in southwest Ohio remained at earlier levels and actually fell among whites in Atlanta. These results indicate the increasing importance of prenatal diagnosis and selective abortion in the epidemiology of Down syndrome and of correcting for it when comparing incidences between populations, even within the same time period. These data from 2 decades show that differences in both observed and expected incidences of Down syndrome exist between both populations and races, principally because of differences in demographic age structure and maternal age fertility rates and because of differential use of prenatal diagnosis and selective abortion. PMID- 8484374 TI - Breast cancer risk associated with abnormal cytology in nipple aspirates of breast fluid and prior history of breast biopsy. AB - The authors previously reported an increased risk of breast cancer in women from the San Francisco Bay Area first enrolled between 1973 and 1980 with proliferative cytologic findings (hyperplasia, moderate hyperplasia, and atypia) compared with women with normal cytologic findings in breast fluids obtained by nipple aspiration and with women from whom breast fluid could not be obtained. To look for factors which might modify the risks associated with cytology, the authors examined several standard breast cancer risk factors: parity, age at first pregnancy, age at menarche, family history of breast cancer, and prior history of breast biopsy. Among women aged 30 years or over, only prior biopsy modified the effect of proliferative cytologic findings on the risk of breast cancer (p < 0.10). For those women with no prior biopsy, breast cancer incidence was 5% (47 of 985) among women with normal cytology and 5% (13 of 277) among women with proliferative findings, whereas among those women with normal cytology and 18% (11 of 62) among women with proliferative cytology. Age-adjusted as well as multivariate-adjusted relative risks indicated that the increased risk of breast cancer associated with proliferative cytologic findings was largely confined to women who had a prior history of breast biopsy. PMID- 8484375 TI - Childhood asthma and indoor environmental risk factors. AB - In a case-control study carried out in Montreal, Quebec, Canada, between 1988 and 1990, indoor environmental factors were studied in relation to the incidence of asthma among 3- and 4-year-old children. Cases (n = 457), whose parents were recruited at a hospital emergency room, were children who had a first-time diagnosis of asthma (International Classification of Diseases, Ninth Revision, code 493) made by a pediatrician. Controls (n = 457) were chosen from family allowance files and were matched with case children on age and census tract. A telephone interview was administered to the children's parents. A 20% feasibility subsample was chosen to wear a nitrogen dioxide monitoring badge during a 24-hour period. Multiple conditional logistic regression analysis showed that after personal susceptibility factors were controlled for, the following were independent risk factors for asthma: the mother's heavy smoking (odds ratio (OR) = 2.77, 95% confidence interval (CI) 1.35-5.66), use of a humidifier in the child's room (OR = 1.89, 95% CI 1.30-2.74), and the presence of an electric heating system in the home (OR = 2.27, 95% CI 1.42-3.65). The presence of other smokers in the home was not quite significant (OR = 1.82, 95% CI 0.98-3.38). A history of pneumonia, the absence of breast feeding, and a family history of asthma were also significant risk factors. In a separate unmatched multivariate analysis of subjects who had worn the nitrogen dioxide badge, there was a dose response relation between nitrogen dioxide (in parts per billion) and asthma. These results confirm the role of susceptibility factors in asthma and show that indoor environmental factors contribute to the incidence of asthma. PMID- 8484376 TI - Maintaining mobility in late life. I. Demographic characteristics and chronic conditions. AB - To assess the role of demographic factors and chronic conditions in maintaining mobility in older persons, this study utilized longitudinal data collected as part of the Established Populations for Epidemiologic Studies of the Elderly between 1981 and 1987 on 6,981 men and women aged 65 years and older in East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. Results are presented for those who at baseline reported intact mobility, defined as the ability to climb stairs and walk a half mile without help, and who were followed annually for up to 4 years for changes in mobility status. Age, income, education, and chronic conditions present at baseline and occurring during follow-up were evaluated for their association with loss of mobility. Over the follow-up period, 55.1% of subjects maintained mobility, 36.2% lost mobility, and 8.7% died without evidence of mobility loss prior to death. In both men and women, increasing age and lower income levels were associated with increased risk of losing mobility, even after controlling for the presence of chronic conditions at baseline. After adjustment for age, income, and chronic conditions, lower education levels were a significant risk factor for mobility loss in men, but not in women. Baseline reports of previous heart attack, stroke, high blood pressure, diabetes, dyspnea, and exertional leg pain were associated with small but significant risks for mobility loss. There was a stepwise increase in the risk of mobility loss according to the number of chronic conditions present at baseline that was very consistent between men and women. The occurrence during the study of a new heart attack, stroke, cancer, or hip fracture was associated with a substantially greater risk of mobility loss than was associated with the presence of these conditions at baseline. PMID- 8484377 TI - Maintaining mobility in late life. II. Smoking, alcohol consumption, physical activity, and body mass index. AB - While positive health behaviors have been shown to extend life, their association with extending active life has not been well investigated. In this report, several health behaviors were investigated in relation to maintaining mobility during 4 years of follow-up among 6,981 men and women aged 65 years and older with intact mobility at baseline between 1981 and 1983 who lived in one of three communities: East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. Intact mobility, defined as the ability to climb up and down stairs and walk a half mile, was determined annually by interview, and study subjects were classified into one of three categories at the end of 4 years of follow-up: 1) maintained mobility (55.1%); 2) lost mobility (36.2%); or 3) died without evidence of having lost mobility prior to death (8.7%). After adjustment for age and all of the health behaviors, risk of losing mobility was significantly associated with current smoking, not consuming alcohol compared with small-to-moderate amounts of alcohol consumption, high (> 80th percentile) compared with moderate (21-80th percentiles) body mass index, and low physical activity levels in both men and women. These findings suggest that positive health behaviors can not only extend longevity but also reduce the risk of losing mobility and independence in later life. PMID- 8484378 TI - Predictors of decline in social relationships in the rural elderly. AB - Prospective evidence for predictors of decline in social relationships over a 3 year follow-up period in an elderly cohort are presented. The cohort consisted of men (n = 903) and women (n = 1,673) over age 65 years in two rural Iowa counties who were interviewed in 1982 and again in 1985. Three separate measures of social relationships were dichotomized into lower and higher levels and included the number of close friends and relatives (less than three vs. three or more), church attendance (less than once per month or not at all vs. once per month or more), and membership in a group (nonmember vs. member). Those with higher social relationship levels at both interviews were compared with those who had higher levels at baseline but lower levels at follow-up (i.e., a decline in social relationship level) using logistic regression. In multivariate analysis, important baseline predictors of decline in social relationship levels included greater age, lower educational level, lower memory test score, the presence of physical disabilities, and a higher level of depressive symptoms. Marital status and lower self-perceived health status were less consistent predictors, and having any living children, history of major illness, and continence status were generally not important predictors of decline in social relationship levels. These findings underscore the multifactorial and complex influences on changes in social relationships, but they also identify factors for possible prevention and intervention strategies. PMID- 8484379 TI - Relation of smoking and low-to-moderate alcohol consumption to change in cognitive function: a longitudinal study in a defined community of older persons. AB - To determine whether smoking habits and alcohol consumption are related to changes in cognitive function, the authors conducted a prospective, community based study of persons aged 65 years and over in East Boston, Massachusetts. In 1982 and again in 1985, the subjects were given three brief tests of cognitive function: immediate memory, digit span, and a mental status questionnaire, which primarily assessed orientation. The 1,201 individuals who performed well in 1982 were included in linear regression analyses of 3-year change in performance, adjusted for age, sex, education, and income. Relative to nonsmoking, current smoking, past smoking, and pack-years were not significantly related to change in immediate memory. None was significantly related to change in orientation. Only pack-years was significantly related to normal change score in digit span (normal change score change per unit of predictor = 0.001, 95% confidence interval 0.0003 0.002). Low-to-moderate alcohol consumption during the month preceding baseline testing was not significantly related to a subsequent 3-year change in performance in two of the three tests. However, people who consumed a very small amount of alcohol had a normal change score that was 0.088 (95% confidence interval 0.015-0.160) better for digit span than did nondrinkers. This study provides evidence that the reported levels of smoking and alcohol use among older persons are not consistent or substantial predictors of the longitudinal change in cognitive function observed in a community. PMID- 8484380 TI - Differences in risk factors for human immunodeficiency virus type 1 seroconversion among male and female intravenous drug users. AB - To examine sex-specific risk factors for human immunodeficiency virus (HIV) type 1 seroconversion among intravenous drug users, the authors conducted a nested case-control study in Baltimore, Maryland, from 1988 to 1992 comparing 146 seroconverters and 539 HIV seronegative controls. Controls were matched on sex, race, date of study entry, and duration of follow-up. Risk factor data were obtained from interviews conducted at the first seroconversion visit for the case and the closest visit for the corresponding seronegative control. Since test results were not available until several weeks after interview, both interviewers and participants were unaware of seroconversion status at the time of interview. When data were analyzed using conditional logistic regression techniques, the variables which were significantly associated with seroconversion among male intravenous drug users included age less than 35 years, a sexually transmitted disease within the past 6 months, lifetime history of syphilis, and current intravenous drug use with an abscess at the injection site. Among women, only a history of three or more sex partners was positively associated with seroconversion and having a biological child under age 18 years was inversely associated with HIV seroconversion. Although the small sample size may have limited the ability to ascertain differences in risks of seroconversion among males and females, these data suggest that sexual transmission contributes to HIV infection among intravenous drug users, especially women. PMID- 8484381 TI - Risk of human immunodeficiency virus infection from unprotected receptive anal intercourse increases with decline in immunologic status of infected partners. AB - To determine whether human immunodeficiency virus (HIV) type 1 infection among unprotected receptive anal partners of HIV type 1-infected men varies by the immunologic status of the HIV type 1-infected index case, 187 sexual partners of 164 HIV type 1-infected index subjects were enrolled at a community health center in Boston, Massachusetts, from 1985-1990. All subjects were interviewed regarding their sexual practices and tested for HIV type 1. Fifty-seven of the 187 sexual partners were infected with HIV type 1. The strongest risk factor for HIV type 1 infection among these partners was unprotected receptive anal intercourse with a known HIV type 1-infected index subject (odds ratio (OR) = 7.2, 95% confidence interval (CI) 3.1-16.3). The risk of unprotected receptive anal intercourse was highest among partners of HIV-infected index subjects who had a T lymphocyte subset ratio of 0.50 or less (OR = 11.4, 95% CI 3.0-43.5) compared with partners of HIV type 1-infected index subjects with a T cell ratio of greater than 0.50 (OR = 5.3, 95% CI 1.9-15.2). After adjustment for confounding, the risk of HIV type 1 infection remained substantially higher among sexual partners who had had unprotected receptive anal intercourse with infected index subjects with a T lymphocyte subset ratio of less than or equal to 0.50 (OR = 7.0, 95% CI 1.8-28.0) compared with partners who had had unprotected receptive anal intercourse with infected index subjects with a T cell ratio of greater than 0.50 (OR = 3.3, 95% CI 1.1-10.0). It would appear that the risk of HIV type 1 infection from unprotected receptive anal intercourse increases as the immunologic status of the HIV type 1-infected insertive anal partner decreases. PMID- 8484382 TI - Epidemiology of human immunodeficiency virus type 1 infection among homosexual men participating in hepatitis B vaccine trials in Amsterdam, New York City, and San Francisco, 1978-1990. AB - Homosexual/bisexual men from Amsterdam, The Netherlands, New York, New York, and San Francisco, California, were entered into trials of the efficacy of hepatitis B vaccine shortly before the acquired immunodeficiency syndrome (AIDS) epidemic was recognized (1978-1980). The authors analyzed data, including serial blood samples tested for antibody to human immunodeficiency virus type 1 (HIV-1) as well as demographic and behavioral information, to characterize the spread of HIV 1 infection within the cohorts. By the end of 1982, the cumulative incidence of HIV-1 infection within the cohorts. By the end of 1982, the cumulative incidence of HIV-1 infection was 7.5% in Amsterdam, 26.8% in New York City, and 42.6% in San Francisco. Covariate analysis showed that differences in sexual activity (number of male sexual partners) and correlates of sexual activity (age and hepatitis B incidence) accounted for the differences in incidence of HIV-1 infection between the New York City and San Francisco cohorts. These covariates did not explain the lower incidence in the Amsterdam cohort. In conclusion, significant differences were found in the spread of HIV-1 in cohorts of homosexual men in Amsterdam, New York City, and San Francisco. These dissimilarities were probably due to a combination of differences in sexual activity at the time the epidemic began and a later introduction of HIV-1 in Amsterdam. PMID- 8484383 TI - Dietary patterns associated with a low-fat diet in the national health examination follow-up study: identification of potential confounders for epidemiologic analyses. AB - To identify systematically the nutrient and food group intakes associated with a low-fat diet, the authors used the detailed dietary information collected from 10,306 individuals aged 32-86 years in the 1982-1984 National Health Epidemiologic Follow-up Study. Intakes of vitamin C and percentages of calories from carbohydrates, dietary fiber, poultry, low-fat dairy products, fruits, vegetables, cereals, and whole grains were markedly higher, while intakes of protein, total fat, saturated fat, oleic and linoleic acids, cholesterol, sodium, all red meats, high-fat dairy products, eggs, nuts, white bread, fried potatoes, desserts, fats, and oils were much lower in the quartile with the lowest percentage of calories from fat. These dietary patterns associated with a low-fat diet were essentially constant across strata of age, sex, race, and socioeconomic status. This study suggests that individuals on a low-fat diet substitute certain carbohydrate-rich foods such as fruits and vegetables for fat. Given these associations between low-fat diets and other dietary factors independently associated with certain cancers, these dietary factors should be considered potential confounders in studies of dietary fat and these cancers. PMID- 8484384 TI - Re: "Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women". PMID- 8484385 TI - p53 expression in incidental prostatic cancer. AB - Incidental prostate cancer is an indolent disease typically characterized by a benign clinical course. This is not clearly established, however, as recent reports suggest that up to 27% of cases progress with long-term follow-up. The indolent history of this disease led initially to the hypothesis that mutations of the p53 gene would be an infrequent event in this patient population. Archival specimens from 24 patients with Stage A1 carcinomas were evaluated for abnormal p53 expression. In 23 patients the disease was diagnosed after transurethral resection for bladder outlet obstructive symptoms, and in one patient after a radical prostatectomy. Using a monoclonal antibody (PAb 240) and an immunohistochemical technique, a total of 36 microfoci of tumor were evaluated. Thirteen (36%) microfoci were positive with an intense nuclear staining pattern (2+), and eight (22%) microfoci had an intermediate staining pattern. Four areas of prostatic intraepithelial neoplasia also stained positively with a 2+ staining pattern. These results suggest that abnormal p53 expression is a feature of a significant number of incidental prostatic carcinomas and that this occurrence is an early event in the development of the malignant phenotype. PMID- 8484386 TI - Machiavellianism in medical students. AB - To be more responsive to the nation's health needs, medical educators should identify those personal qualities associated with effective primary medical care. For this research Machiavellianism was chosen as a tracer character trait opposed to the characteristics embodied in an ideal family physician. A survey was conducted of 167 freshmen from one medical school and 823 seniors from four medical schools, with Machiavellianism scores used to predict their professional role characteristics, attributional style toward patients, and choice of a career specialty. Results showed that 15% of all students scored positively on the Machiavellianism scale. Mean Machiavellianism scores for seniors did not differ from those for freshmen. Men had higher Machiavellianism scores than women. Those students with high Machiavellianism scores relied excessively on high-tech medicine and were externally controlled, intolerant of ambiguity, and authoritarian. Seniors' high Machiavellianism scores predicted a negative attributional style toward geriatric and hypochondriac patients, thereby validating the use of Machiavellianism to measure medical students' indifference to patients and their problems. PMID- 8484387 TI - Ibuprofen fails to increase plasma growth hormone levels in humans. AB - In eight healthy volunteers, basal and arginine-stimulated plasma glucose and growth hormone levels were determined during administration of a placebo and after 3 days of ibuprofen (800 mg four times daily). Ibuprofen had no significant effect on basal or stimulated plasma glucose or growth hormone levels. As is not the case with indomethacin, ibuprofen fails to increase basal and arginine stimulated plasma growth hormone levels. This suggests that the effect of indomethacin on growth hormone secretion is due to a mechanism unrelated to inhibition of prostaglandin synthesis. PMID- 8484388 TI - Primary spontaneous pneumothorax in men. AB - To determine the risk factors, clinical presentation, and long-term outcome of primary spontaneous pneumothorax (PSP), all available cases of PSP in the Israeli Defense Forces (IDF) were retrospectively reviewed. Using the computerized IDF database, all men who had pneumothorax were identified and a telephone interview obtained with 343 individuals, 286 of whom had PSP and agreed to participate in this study. These 286 persons experienced 498 episodes of PSP, with 314 medical records available for review. Average length of follow-up from the first episode of PSP was 107.2 months. Of the study population, 11.5% had a positive family history for PSP. The height-to-weight ratio was significantly and positively correlated with the number of PSP episodes per person, with the regression coefficient being 0.49. The age distribution of those with PSP had a monophasic pattern, with the average age being 25.3 years on first episode. More than one episode of PSP occurred in 41.3% of patients. No ipsilateral recurrences were observed after surgery. Treatment with a sclerosing agent seemed to be more effective in preventing ipsilateral recurrences of PSP than chest tube insertion alone (26.5% vs. 38.3%). Primary spontaneous pneumothorax is an important medical problem, especially in men of military age. It has a significant inherited component in its etiology, with asthenic body build being an additional risk factor. Based on a literature review and the data obtained from this study, it was concluded that chest tube insertion with intrapleural instillation of a sclerosing agent is the preferred nonsurgical invasive treatment modality in PSP. PMID- 8484389 TI - Case report: silent thyroiditis after adrenalectomy in a patient with Cushing's syndrome. AB - A case of silent thyroiditis after unilateral adrenalectomy for treatment of Cushing's syndrome is reported. The left adrenocortical adenoma was resected. Glucocorticoid was replaced after the operation and was gradually tapered. Thyrotoxic symptoms with painless goiter occurred 9 months after the adrenalectomy when a replacement dose of prednisolone was tapered to 5 mg/d. Plasma-free thyroid hormones increased and thyrotropin was suppressed. Thyroidal uptake of radioactive iodine was extremely low. Both titers of antimicrosomal and antithyroglobulin antibodies stayed at high levels throughout the observation period from the preoperative stage. Normalization of thyroid functions was obtained 3 months after the onset of thyrotoxicosis with beta-adrenergic blocker alone. It was speculated that exposure to a large amount of endogenous and supplementary exogenous glucocorticoid protected the patient's immune system from autoimmune attack of thyroid antigens and that tapering of the supplementary glucocorticoid caused exacerbation of immune responses, resulting in overt thyroid dysfunction even 9 months after adrenalectomy. PMID- 8484390 TI - Case report: alpha G-Philadelphia, beta O-Arab, and beta C globins present in a single patient. AB - The case of a 7-month-old Nigerian child who presented with anemia and microcytosis is described. Hemoglobin electrophoresis studies revealed a band with pronounced cathodic mobility. This represented a heterohybrid hemoglobin tetramer composed of an alpha-globin mutant, G-Philadelphia (alpha GPhil), and two variant beta-globin chains, beta C and beta O-Arab. The absolute amounts of alpha GPhil found in the propositus were less than expected for an alpha 2-globin gene product. It has not been established whether alpha G-Philadelphia interacting with beta O-Arab and beta C globin chains is the cause of the microcytosis. PMID- 8484391 TI - Case report: effects of iron deficiency and the -88 C-->T mutation on HbA2 levels in beta-thalassemia. AB - Hemoglobin A2 levels in members of an African American family with -88 C-->T beta(+)-thalassemia were measured, and two patients in whom iron deficiency anemia developed were evaluated during treatment. Iron deficiency may diminish the level of HbA2 in healthy control subjects and in patients with heterozygous beta-thalassemia; in addition, it may reduce the amount of variant hemoglobin in certain hemoglobinopathies. Although iron deficiency appeared to be associated with a reduction in HbA2 quantity in the patient with heterozygous beta thalassemia, the level of HbA2 did not fall below the range characteristic of beta-thalassemia. It had been proposed that mutations in the beta-globin gene promoter may be associated with higher-than-expected levels of HbA2. However, this "mild" beta-globin gene promoter mutation did not seem to result in HbA2 concentrations higher than anticipated in the heterozygous beta-thalassemias. PMID- 8484392 TI - Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs. AB - The effects of renal prostaglandins on medullary blood flow, active chloride transport, and antidiuretic hormone are important in urine dilution. It is surprising, therefore, that drugs that inhibit prostaglandin synthesis rarely cause hyponatremia. A patient in whom hyponatremia developed during ibuprofen administration is described and other reported cases of this association in adults are reviewed. The previous case reports fall into two well defined groups: first, neonates treated with indomethacin for patent ductus, and second, adults, often elderly, who usually have other diseases that impair urinary dilution. Although hyponatremia is a rare consequence of therapy with prostaglandin inhibitors, certain individuals are at increased risk and should be monitored for this side effect. PMID- 8484393 TI - Hypothalamic-pituitary-adrenal function in non-AIDS patients with advanced HIV infection. AB - Patients with acquired immune deficiency syndrome (AIDS) are reported to have increased basal cortisol and reduced stimulated cortisol release, but the dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis is not yet understood in patients with human immunodeficiency virus (HIV) infection during the advanced stage of disease that precedes the development of AIDS. To understand the status of the HPA axis during this phase of HIV infection, 25 non AIDS ambulatory patients with advanced HIV infection and without evidence of adrenal or pituitary insufficiency were studied. Ovine corticotropin-releasing hormone was administered (1 microgram/kg BW) intravenously and plasma cortisol and adrenocorticotropin (ACTH) were measured over the following 120 minutes. Based on a standard response curve, obtained from CRH testing of 10 HIV negative volunteers with no HPA abnormalities, 13 patients were found to have normal response (group 1), 6 patients had reduced ACTH and cortisol response (group 2) and 6 patients had normal ACTH with reduced cortisol response (group 3). Basal cortisol and basal ACTH were comparable for control subjects and groups 1, 2, and 3. This suggests that, in advanced non-AIDS HIV patients with no clinical evidence of pituitary or adrenal disease, about 25% (group 2) have reduced pituitary reserve with high basal ACTH and cortisol, and about 25% (group 3) have reduced adrenal reserve with high basal cortisol and inappropriately normal basal ACTH, whereas about 50% (group 1) maintain normal HPA axis activity with increased basal cortisol secretion. The exact physiopathologic mechanism is not yet known, but an enhanced CRH production by the hypothalamus may explain the alterations in the HPA axis in advanced HIV disease. PMID- 8484394 TI - The acute chest syndrome of sickle cell disease. AB - The acute chest syndrome (ACS), characterized by fever, chest pain, leukocytosis and a new infiltrate on chest roentgenogram, is a common complication of sickle hemoglobinopathies. The major differential diagnoses of ACS are pneumonia and pulmonary vaso-occlusive disease, which may occur simultaneously. Bacterial pulmonary infections are documented infrequently in ACS with the exception being in the pediatric population under 5 years of age. Because there are no clinical or laboratory parameters that clearly allow for distinction between pneumonia and vaso-occlusive disease, empiric use of antibiotics directed against S. pneumoniae and other pathogens commonly seen in community-acquired pneumonias remain a mainstay of therapy. PMID- 8484395 TI - Competing stochastic models of the incubation period: an investigation of age-at diagnosis of familial and sporadic retinoblastoma. AB - This study is based on the assumption that the distribution of age-at-diagnosis (a synonym for the incubation period) of a disease can convey information with respect to its pathogenetic mechanisms. To this end, an analysis of 3 retinoblastoma (RB) international data sets was undertaken. The molecular and cellular basis of RB is well understood and may serve our purpose well. RB is broken down into familial bilateral, unilateral, and sporadic unilateral forms. Survival and hazard functions were computed. Several competing stochastic models (up to 9 per RB form) were fit. Each conveyed a meaningful pathogenetic mechanism. Between-model discrimination was achieved by examining chi-square goodness-of-fit values to select the best fitting model. Well-known survival models, such as the simple exponential and the lognormal (Sartwell model) were ruled out. Age-at-diagnosis of familial RB proved to be best explained by 2 interfering exponentials (a diffonential function); the logistic was retained as the best adjusted model of the incubation period of sporadic cases of RB. As to familial unilaterals, both the diffonential and the logistic models fit equally well. The 3 data sets are consistent in these results, ruling out the less well fit competing models. The results suggest the existence of 2 opposing but independent balancing internal mechanisms at the origin of familial RB. Sporadic RB appears to be due to a single host-dependent self-limiting cellular mechanism. Familial unilaterals which share both of these component mechanisms would involve a lower retinoblast turnover rate. The cellular implications of these findings are discussed with regard to the relative importance of endogenous and exogenous induction factors in RB. It is concluded that, according to the RB form, RB occurrence results from 2 cellular interfering forces of different strength and organization. PMID- 8484396 TI - Chromosome cultures from human cartilage. AB - Choosing the best post-mortem biological tissue source for chromosomal studies is a challenge for cytogeneticists. Acceptable cytogenetic results are difficult to obtain from macerated and necrosed tissues. This report describes a method that is carried out after enzymatic digestion of cartilage from human fetuses and infants. It is currently employed successfully in our laboratory and our experience has shown that human cartilage could well be the tissue of choice for cytogenetic studies in stillborn fetuses and dead infants. PMID- 8484397 TI - Heterogeneity versus variability in megalocornea-mental retardation (MMR) syndromes: report of new cases and delineation of 4 probable types. AB - Megalocornea (corneal diameter > or = 13 mm) is associated with mental and neurological impairment, and minor anomalies in Neuhauser syndrome (megalocornea mental retardation syndrome). Here we report 4 new cases of megalocornea and mental retardation. Those unrelated patients have a consistent pattern of anomalies with possible recessive inheritance which clearly differs from that of the original patients of Neuhauser et al. [1975]. We discuss the heterogeneity of the syndromes with megalocornea and mental retardation. Based on these cases and on a review of the literature, we suggest a provisional clinically oriented classification in 5 subtypes: (1) a recessive form type Neuhauser (with iris hypoplasia and minor anomalies), (2) a recessive form type Frank-Temtamy (with camptodactyly, scoliosis and growth retardation), (3) a recessive type 3, including our 4 personal cases (with normal irides, severe hypotonia, relative or absolute macrocephaly and minor anomalies), (4) a possible Frydman type (with normal irides, megalencephaly and obesity), and (5) provisionally unclassifiable cases. PMID- 8484398 TI - Brachydactyly, mesomelia, mental retardation, aortic dilatation, mitral valve prolapse, and characteristic face. AB - We report on a male with brachydactyly, thin habitus with narrow shoulders, mesomelic shortness of the arms, long lower face with obtuse mandibular angle, maxillary hypoplasia with beaking of the nose, aortic root dilatation, and mitral valve prolapse. This combination of findings has not been reported previously. PMID- 8484399 TI - 18q-mosaicism associated with Rett syndrome phenotype. AB - Rett syndrome consists of a characteristic progressive encephalopathy in females. The cause of this syndrome is unknown. We present a patient with 18q-mosaicism who, along with the characteristics of this autosomal deletion, also fulfills the clinical criteria for Rett syndrome. This may demonstrate heterogeneity within this as yet clinically defined syndrome. A thorough chromosomal analysis should be performed in suspected cases of Rett syndrome. PMID- 8484400 TI - Proteus syndrome with cardiomyopathy and a myocardial mass. AB - Proteus syndrome is an overgrowth syndrome principally affecting cutaneous and skeletal tissues, accompanied by subcutaneous hamartomas. We report on a patient with predominantly skeletal and visceral involvement, including a cardiac mass and thickening of the myocardial septum affecting cardiac conduction and contraction. PMID- 8484401 TI - Decrease in calcitonin-containing cells in truncus arteriosus. AB - Experimental studies in chick embryos have demonstrated that truncus arteriosus (TA), a form of conotruncal cardiac defect, is due to abnormalities in the cranial neural crest. However, no data are available to support this hypothesis in humans with isolated TA. In the present study, the assessment of calcitonin immunoreactive cells (C-cells) has been employed to evaluate whether or not the proportion of thyroid cells derived from the cranial neural crest is normal in patients with isolated TA. Thyroid sections from 15 such patients in which no other extracardiac malformations were neither clinically nor pathologically found, and from 11 control age-matched patients were studied immunohistochemically at autopsy in order to determine the number and distribution of calcitonin-containing cells. The volume density of C-cells (0.888%) and the number of C-cells per follicle (0.991) was significantly lower in patients with TA than in control patients (3.475%, and 2.367, respectively). The decrease of neural crest-derived cells in the thyroid of patients with "isolated" TA documents more extent abnormalities than clinically suspected and supports the hypothesis of neural crest disturbance as the pathogenetic factor responsible for this heart malformation. PMID- 8484402 TI - Effect of laboratory or clerical error on presymptomatic risk calculations for Huntington disease: a simulation study. AB - Linked markers are useful in prenatal diagnosis as well as presymptomatic diagnosis in late age-of-onset diseases such as Huntington disease (HD). It is widely assumed that most laboratory or clerical errors will be detected because of incompatibility of marker haplotypes within the family. However, errors in marker phenotypes that are compatible but wrong may result in a consultand being given an incorrect risk estimate. We have addressed this issue using simulated marker data in pedigrees similar to those seen in our HD testing program. In Family Structure I (an 11-member, 3-generation family), a particular family was more likely to be detected as inconsistent than incorrectly assigned. In a small nuclear family (Family Structure IV), fewer errors would be detected, and more would appear consistent but give incorrect risk estimates (e.g., low risk misclassified as noninformative or high). Given the presence of tight linkage, risk estimates are often calculated based on a small number of relatives. However, these computer simulations demonstrated that increasing the number of relatives typed decreases the probability that the family will remain consistent with an error present, and, therefore, decreases the probability of an incorrect assignment of risk. It is important to decrease the level of such errors by duplicated readings of raw marker data and validation of computer input. PMID- 8484403 TI - Segregation analysis of rare autosomal folate sensitive fragile sites. AB - We have studied 12 families with rare autosomal folate sensitive fragile sites (RAFSFS). Of these, 9 were informative for segregation analysis of fragile sites in order to assess differences in parental transmission. We identified 20 families with RAFSFS from the literature from 1985 to 1989; thirteen of these were informative for segregation analysis. Segregation analysis confirmed that paternal fragile site transmission rates deviated significantly from the expected 50% for a Mendelian co-dominant trait. Sex ratio comparisons showed a significant excess of transmitting females and a significant excess of males among fragile site non-carriers from the literature families. Comparison of the fragile site carriers with non-carriers in the combined data showed a non-significant excess of non-carriers. We confirmed a deficiency of offspring expressing fragile sites when transmission was through fathers, suggesting gametic selection or the phenomenon of parental genomic imprinting. PMID- 8484404 TI - Severe nonspecific X-linked mental retardation caused by a proximally Xp located gene: intragenic heterogeneity or a new form of X-linked mental retardation? AB - X-linked mental retardation (XLMR) can be subdivided into syndromic and nonsyndromic or nonspecific. Patients with non-syndromal XLMR show no characteristic manifestations, biochemical defects, or distinct fragile sites. Nevertheless, nonspecific XLMR seems to be heterogeneous. To determine the number and location of the genes responsible for XLMR, linkage studies in large pedigrees have to be performed. Here we report the data of linkage analysis in a large Brazilian family with 7 patients affected by a severe form of XLMR, with no other associated malformations. All the obligate carriers are normal. A close linkage without recombination (lod scores 1.95 and 3.25) was found between the disease locus and polymorphic DNA loci DXS255 (Xp11.22), DXS14 (Xp11.21). These results suggest that the gene responsible for the disease in this family maps in the Xp11-cent of the X chromosome. Positive lod scores in this region have also been reported for other XLMR genealogies, but with a much milder phenotype. The possibility of intragenic or locus heterogeneity is discussed. PMID- 8484405 TI - Index finger hyperphalangy and multiple anomalies: Catel-Manzke syndrome? AB - We describe a boy with short stature, developmental delay, unusual face, right iris coloboma, malformed ears, micrognathia, and skeletal anomalies including hyperphalangy of the index fingers, bilateral fifth finger clinodactyly, short halluces, and scoliosis. Internal anomalies included asymmetric and dilated cerebral ventricles and ventricular septal defect. The neonatal history of small jaw with feeding and respiratory difficulties suggested a Pierre Robin sequence, but there was no cleft palate. Two maternal uncles with similar anomalies had died at ages 13 months and 5 years, respectively. RFLP studies with the DNA probes DXS72 and F8C were consistent with but not diagnostic of X-linked recessive inheritance. The pattern of anomalies was compatible with a diagnosis of Catel-Manzke syndrome, but a novel dysostosis syndrome must also be considered. PMID- 8484406 TI - New lethal syndrome of fetal akinesia with characteristic facial appearance, severe microphthalmia, microtia, and truncus arteriosus in two male sibs. PMID- 8484407 TI - Mutations in von Recklinghausen neurofibromatosis: an hypothesis. AB - Von Recklinghausen neurofibromatosis or neurofibromatosis type I (NF1) is a relatively frequent (1/3,000 livebirths) autosomal dominant condition. Some unusual aspects are noted in this disorder: new mutations are frequent and almost all are of paternal origin without parental age effect. The recurrence of NF1 among children of healthy parents is rare as opposed to other dominant disorders. I propose that in NF1 (1) new mutations occur often in somatic cells or in late germinal cells, however, they occur very rarely in early germinal cells leading to germinal mosaicism and (2) the individual with somatic mosaicism presents symptoms of the disease. Therefore, an NF1 patient with an apparent new mutation is often a somatic mosaic for the mutation and if the mosaic is also present in germinal cells some of his children will be affected. This hypothesis may explain the unusual aspects of mutation in NF1. PMID- 8484408 TI - Vascular anomalies in campomelic syndrome. AB - We report on 4 patients with the campomelic syndrome (CS) in whom postmortem angiography of the lower limbs was performed. Of the 4 patients, 3 were phenotypic females (2 of them with a 46,XY karyotype) and one was a male with a normal 46,XY karyotype. Three fulfilled the criteria of CS, and one (phenotypically female with a 46,XY karyotype) lacked the lower limb bowing and the talipes equinovarus typical of CS. This infant may constitute a further example of the recently reported CS without campomelia. The results of the angiographic study are compared with 46 postmortem angiographies of normal fetuses and newborn infants at different gestational ages. In the first 3 CS patients the main arterial axis of the lower limb, formed by the superficial femoral and anterior tibial arteries, had smaller diameters than expected while the profunda femoris and posterior tibial arteries had greater diameters than age matched controls. However, the most striking abnormality was the absence or marked deficiency of the anterior tibial artery. Its terminal branch, the dorsalis pedis artery, was also absent and the plantar arch was abnormally formed by the posterior tibial artery either alone or in conjunction with the peroneal artery. The normal arterial pattern was found in the patient who lacked bowed bones. This finding supports a developmental association between vascular defects and lower limb anomalies in CS. This aberrant arterial pattern in CS may affect or be affected by muscle development. The shortness of the posterior femoral and calf muscles fix the knee and the ankle joints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484409 TI - Trisomy 4 in a fetus with cyclopia and other anomalies. AB - We report on an 18-week fetus with cyclopia, alobar holoprosencephaly, complex congenital heart defect, anal atresia, oligosyndactyly, cystic hygroma, and skeletal abnormalities with trisomy 4. Structural anomalies were detected on routine ultrasound of the pregnancy of a 17-year-old G3 P1 TAB1 woman with sickle cell trait. Trisomy 4 conceptuses usually miscarry in the first trimester. We are aware of no other reports of a fetus with trisomy 4 and cyclopia. Causal association of chromosome abnormalities and holoprosencephaly sequence may be more apparent in embryos and early fetuses than term fetuses because of poor viability of affected conceptuses. PMID- 8484410 TI - Bromodeoxyuridine induces chromosomal fragile sites in the canine genome. AB - Peripheral blood lymphocytes from 3 clinically normal domestic dogs were cultured for bromodeoxyuridine (BrdU) induction of fragile site expression. BrdU induced fragile site expression in cells from all 3 dogs. The mean percent of cells with fragile sites and the mean number of fragile sites per cell were significantly increased in all BrdU incubated cultures compared to control cultures. The frequency of BrdU fragile site expression did not vary significantly among the dogs. Lymphocytes from all 3 dogs expressed BrdU induced autosomal fragile sites. Two BrdU induced fragile sites were identified on the long arm of chromosome 1, one of which was close to or coincident with a previously identified folate sensitive fragile site on this canine chromosome. Lymphocytes from the 2 female dogs also expressed BrdU induced fragile sites on the X chromosome, but BrdU failed to induce fragile sites on the X chromosome from the one male dog in the study. The 2 BrdU-induced fragile sites identified on the long arm of the X chromosome were close to, or coincident with 2 previously described folate sensitive common fragile sites on the canine X chromosome. This is the first report of induction of BrdU-inducible fragile sites in the genome of the domestic dog. PMID- 8484411 TI - Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. AB - An apparently autosomal recessive syndrome of hereditary vitreoretinal degeneration (VRD) with retinal detachment, high myopia, and congenital encephalocele was described in 1971 by Knobloch and Layer [J Pediatr Ophthalmol 8:181-184]. Clinical confirmation of the presence of encephaloceles was lacking, and no neuropathologic studies were reported. We have evaluated a similarly affected family with 2 sibs with high myopia, VRD, and occipital scalp defects. Histologic examination of the scalp defects showed heterotopic neuronal tissue in both instances. The older girl has had a unilateral retinal detachment. Her other eye and both eyes of the younger sib have so far been treated successfully with prophylactic retinal cryotherapy. Both children have normal to above normal intelligence. The family reported by Knobloch and Layer [1971] and the sibship herein described appear to represent a distinct autosomal recessive trait. Analysis of the associated defects suggests an underlying defect in early cephalic neuroectodermal morphogenesis. Data from these families imply that congenital occipital scalp defects rather than true encephaloceles may, as is true in some cases of Meckel syndrome, accompany Knobloch syndrome. The presence of a congenital midline scalp defect should alert the clinician to possible underlying central nervous system and/or ocular pathology and should lead to consideration of further diagnostic evaluations and prophylactic measures. PMID- 8484412 TI - Long-term outcome of Hurler syndrome following bone marrow transplantation. AB - Previous reports suggested a therapeutic response of lysosomal storage diseases such as Hurler syndrome following bone marrow transplantation. However, a clearer understanding of outcome has awaited long-term follow-up. We evaluated prospectively 11 consecutive patients with Hurler syndrome receiving marrow from an HLA-identical sib donor between September 1983-October 1988. Follow-up evaluations included assessment of donor engraftment by restriction fragment polymorphism analysis, determination of leukocyte alpha-L-iduronidase level, measurement of lumbar cerebrospinal fluid (CSF) pressure, computerized tomography (CT) of the brain, and psychometric testing. In this series there was a survival rate of 9/11 (82%) with all survivors showing complete (7 patients) or partial (2 patients) donor engraftment. Prospective longitudinal evaluation of the 9 surviving children, now 3.8-8.9 years posttransplantation (median 5.5) demonstrated persistence of previously deficient leukocyte alpha-L-iduronidase at levels reflecting the donor genotype and degree of donor engraftment. Urinary glycosaminoglycan excretion declined to near-normal within 5 months of donor engraftment. Prior to treatment, 7 of 8 children studied were found to have occult intracranial hypertension (lumbar CSF pressure > 20 cm CSF); however, all surviving children attained normal or near-normal pressure within 18 months of donor engraftment. Longterm follow-up CT imaging of the brain did not show progressive volume loss (cerebral atrophy) after donor engraftment. Of 9 survivors, 4 children having a developmental quotient (DQ, Mental Development Index on Bayley Scales of Infant Development) above 80 prior to transplantation subsequently maintained IQ scores above this level. However, 5 patients with lower pretransplant DQ scores now have significant cognitive deficits and attention deficit hyperactivity disorder. Progressive brain damage resulting from communicating hydrocephalus may be prevented by successful engraftment. Early transplantation of children with Hurler syndrome who have normal intelligence is likely to have the clearest benefit because long-term intellectual outcome will be limited by brain damage which has occurred prior to treatment. PMID- 8484413 TI - Autosomal dominant preaxial deficiency, postaxial polydactyly, and hypospadias. AB - We report on 3 individuals, a man and his son and daughter, who were born with preaxial deficiencies of the hands and feet and postaxial polydactyly of the hands. Both males also had glandular hypospadias. Certain of these findings resemble those found in the hand-foot-genital syndrome; however, we conclude that this family has a hitherto unreported autosomal dominant condition. Production by a single gene defect of preaxial deficiencies and postaxial polydactyly in the same individual is of note. PMID- 8484414 TI - Bone dysplasia, midface hypoplasia, and deafness: three new patients and review of the literature. AB - We report on 3 unrelated patients with a syndrome of sensorineural deafness (3/3), midface hypoplasia (3/3), disproportionate shortness with short limbs (3/3), cleft palate or bifid uvula (3/3), and lack of high myopia (3/3). This brings the number of reported patients with this condition to 11. Different names such as oto-spondylo-megaepiphyseal dysplasia (OSMED) or the Insley-Astley syndrome have been used. We propose the name "syndrome of bone dysplasia, midface hypoplasia, and deafness" which lists the 3 main manifestations of the condition. PMID- 8484415 TI - New multisystemic disorder involving heart valves, skin, bones, and joints in two brothers. AB - We report on 2 brothers with a severe progressive disorder characterized by thick skin, acne conglobata, "coarse" face, osteolysis, gingival hypertrophy, brachydactyly, camptodactyly, and mitral valve prolapse. The youngest brother died at age 24 years because of heart failure. Biochemical and pathological studies excluded known metabolic diseases. We think that this is a new genetic disorder inherited in autosomal recessive or X-linked recessive manner. PMID- 8484416 TI - On Charles Darwin and other great men in correspondence with Carl Wilhelm von Naegeli. PMID- 8484417 TI - Charles Darwin and other great men in correspondence with Carl Wilhelm von Naegeli. AB - The great Swiss-German botanist Carl Wilhelm von Naegeli (1817-1891) was a student of Lorenz Oken, A.P. de Candolle, and Matthias Jacob Schleiden and became a key figure in "genetic" (i.e., evolutionary-developmental) biology in the mid late 19th century. He was an expert on the hawk-weed, Hieracium and also made important contributions to microbiology. One of his many outstanding students was Carl Correns, one of the 3 rediscoverers of Mendel's work. Naegeli was an early proponent and defender of Darwin. The correspondence preserved in the Naegeli family contains many important letters between Naegeli and his contemporaries. Those from Mendel to Naegeli have passed out of the Naegeli family and were published by Correns earlier in the century. However, exceptionally notable items still in the archives of the Naegeli family include 4 surviving letters from Darwin, 2 letters from Virchow, and 10 from Justus von Liebig. In spite of a lack of appreciation of Mendel's work, we call attention to the importance of those surviving documents from an era in which very few of the greatest naturalists and founders of modern biology--including Goethe, Darwin, Galton, Agassiz, von Humboldt, von Baer--were without "blind spots." PMID- 8484418 TI - Microcephaly in Rubinstein-Taybi syndrome. PMID- 8484419 TI - Manifestation of heterozygosity in Papillon-Lefevre syndrome? PMID- 8484420 TI - Inbreeding among medical geneticists. PMID- 8484421 TI - Clinical practice and service delivery: getting back on track. PMID- 8484422 TI - The future in the making: recent trends in the work-family interface. AB - Following a review of recent demographic trends in family life and gender roles, and of new developments in the American economy, their interactive effects are discussed. Directions for socioeconomic change are then suggested with a view to easing the burden on married adults that results from the combination of family and work obligations. PMID- 8484423 TI - Growing up with a psychotic mother: a retrospective study. AB - Nine adults who had been reared by mothers diagnosed with psychosis reported on their childhood experiences. Analysis of the retrospective data revealed the five common themes of abuse and neglect, isolation, guilt and loyalty, grievances about mental health services, and social supports. The resilience and coping strategies of the participants are examined, and implications for therapeutic interventions with such families are discussed. PMID- 8484424 TI - A clinical typology of interparental violence in disputed-custody divorces. AB - From two studies of high-conflict divorcing families in child custody disputes, four characteristic profiles of interparental violence were identified: ongoing or episodic battering by males, female-initiated violence, interactive violence controlled by males, and violence engendered by separation or postdivorce trauma. A fifth profile, culled from a subsample of members of the first two groups, was characterized by psychotic and paranoid reactions. PMID- 8484425 TI - Counseling and psychotherapy with Japanese Americans: cross-cultural considerations. AB - The literature of the past two decades on Japanese-American culture, behavior, and mental health services and issues is reviewed. Counseling and psychotherapy with these clients are then discussed, taking into account traditional Japanese cultural values, with particular emphasis on verbal and nonverbal factors affecting therapeutic approaches and communication. PMID- 8484426 TI - Handling bodies after violent death: strategies for coping. AB - Interviews with and observations of experienced and inexperienced personnel were conducted to determine their coping strategies before, during, and after their work with the bodies of people who had died violently. Avoidance, denial, and social support from the work group and spouse appeared to facilitate coping. The implications of these findings for therapeutic intervention are discussed. PMID- 8484427 TI - Reactions to perinatal loss: a qualitative analysis of the National Maternal and Infant Health Survey. AB - Women who had experienced an infant or fetal death responded to an open-ended question on the 1988 National Maternal and Infant Health Survey about their perinatal experience. A qualitative analysis of the 413 responses identified six major themes, including need for further information, problems with the mourning process, and unresolved questions about the cause of the death. Implications of the findings for health care practice are discussed. PMID- 8484428 TI - Mental health status of Cambodian refugees ten years after leaving their homes. AB - The mental health status of a general population sample of Cambodian refugees living in the United States was assessed ten years after they had left their homes in Cambodia. Subjects were found to be experiencing extremely high levels of post-traumatic stress disorder, dissociation, depression, and anxiety. Ninety percent of these refugees exhibited marked symptomatology in one or more of these categories. PMID- 8484429 TI - Divorced women: individual differences in stressors, mediating factors, and adjustment outcome. AB - Individual differences in exposure and response to stress in a sample of 56 divorced mothers were examined. Compared with normative data, the sample reported significantly more negative life events, more psychiatric symptoms, and poorer social adjustment. Social support and income emerged as the mediating factors most strongly associated with adjustment outcome. PMID- 8484430 TI - Threat of missile attacks in the Gulf War: mothers' perceptions of young children's reactions. AB - Mothers' perceptions of their infants' and toddlers' reactions to stressors related to the Gulf War were examined. Substantial distress reactions were displayed in somatic symptoms, behavioral disturbances, difficulties in routine functioning, and regressive behavior. Coping reactions were manifested in cooperative, helpful, and symbolic behavior. Reactions were found to be related to proximity to missile target zones, family reactions, and age of the child. PMID- 8484431 TI - Burdens and gratifications of caregiving: appraisal of parental care of adults with schizophrenia. AB - The caregiving experiences of 60 parents of adults with schizophrenia were investigated for the presence of gratification; the role of the interpersonal caregiver-child relationship; and the effects of burden, gratification, conflict, and intimacy. Results indicate that relationships, as measured by intimacy and conflict, were more highly associated with burden and gratification than were severity of schizophrenic symptoms or degree of caregiving involvement. Implications for therapeutic interventions are discussed. PMID- 8484432 TI - Emotional distress in Israeli women before and after abortion. AB - Emotional distress in a group of Israeli women who requested legal abortion was compared with that in a group of women on the verge of delivery and in a random group of nonpregnant women on measures of anxiety and depression. Emotional consequences of the abortion were evaluated by before-and-after comparisons of the same measures in a subgroup of the aborting women. Findings indicated significantly greater distress in the aborting women, with lower levels after the abortion. The effects on emotional well-being of personal and contextual factors and their interactions were also examined. PMID- 8484433 TI - Lesbians and HIV: clinical, research, and policy issues. AB - Sources of risk for HIV infection in members of the lesbian community are surveyed, together with factors that adversely affect access to appropriate health care by women in general and lesbians in particular. Issues of clinical practice, research, and public policy are examined with a view to promoting more effective prevention and treatment strategies. PMID- 8484434 TI - Mood disorders in children with oppositional defiant disorder: a pilot study. AB - The nature and prevalence of comorbid mood disorders were explored in a group of 28 latency-age children diagnosed with oppositional defiant disorder. Findings are preliminary in nature but suggest that children with oppositional defiant disorder are at significant risk for low-grade depressive illness and that this may commonly be overlooked in the presence of their primary disorder's more overt symptoms. PMID- 8484435 TI - Childhood sexual abuse and parental alcoholism: interactive effects in adult women. AB - Symptoms associated with histories of childhood sexual abuse and parental alcoholism were investigated in a sample of 364 university women. A significant association was found in occurrence between the two stressors, and a substantially higher level of symptoms was revealed in women who had experienced both during childhood. PMID- 8484436 TI - Paternal involvement, maternal employment, and adolescents' academic achievement: an 11-year follow-up. AB - An 11-year follow-up study explored the effects of paternal involvement in child rearing and maternal employment in prior years on grades and educational expectations of a group of white, middle-class adolescents from intact families. Past maternal employment was found to be a more powerful predictor of children's academic performance and expectations than was amount of father involvement. Part time maternal employment appeared to be optimal for children's academic expectations. PMID- 8484437 TI - Woman battering in Israel: the relative contributions of interpersonal factors. AB - Interpersonal factors were examined in 60 couples who reported violence by male against female partner and in 60 couples who did not. Violent men reported lower partnership quality and less social support than did nonviolent men. Battered women reported lower partnership quality but more positive social support than did women with nonviolent partners. Level of violence was predicted by level of child-rearing conflict and the availability of social support for the violent men. PMID- 8484438 TI - Munchausen syndrome by proxy: diagnosis and prevalence. AB - A review of the literature and a survey of pediatric neurologists and gastroenterologists yield data indicating that the prevalence of Munchausen syndrome by proxy is greater than is generally estimated. This possibility is further supported by follow-up data on siblings of victims, together with wide variability among practitioners in case identification. PMID- 8484439 TI - Fear, embarrassment, and relief: the tuberculosis epidemic and public health. PMID- 8484440 TI - Talking past each other about risks and the importance of context. PMID- 8484441 TI - A proposal for the mandatory inclusion of helmets with new children's bicycles. AB - To reduce bicycle-related head injuries in children, we propose new regulations be established that mandate the inclusion of approved helmets with the sale of all new children's bicycles. Currently, purchasing a helmet is a separate economic decision that acts as a barrier to helmet ownership and use. The inclusion of a helmet with the bicycle would markedly increase helmet ownership. The increased demand would reduce the manufacturing cost per helmet, so the cost of the bicycle with the helmet would be lower than the current retail price of the two separately. This proposal could potentially be implemented by federal or state legislation, a Consumer Product Safety Commission regulation, or voluntary adoption of a practice or standard by bicycle manufacturers. Increased helmet ownership is necessary but not sufficient to raise helmet use rates. The increased ownership generated by this proposal, complemented by enhanced educational, promotional, and legal interventions, is probably the most practical and cost-effective public health strategy available to increase helmet usage and prevent bicycle-related head injuries in children. PMID- 8484442 TI - Tuberculosis, again. PMID- 8484443 TI - The dual epidemics of tuberculosis and AIDS: ethical and policy issues in screening and treatment. AB - As the recent increase in cases of tuberculosis is addressed, there is a danger that the need for increased protection of the public health will create a climate in which the rights of individuals with tuberculosis and human immunodeficiency virus (HIV) infection may be disregarded. This paper considers ethical and policy issues in the control of tuberculosis. The authors conclude that mandatory HIV testing is not critical to effective tuberculosis control, and that although individuals infected with HIV are at increased risk for developing tuberculosis, exclusionary employment practices are not justified. Because failure to complete the course of tuberculosis treatment increases the prospect that drug-resistant strains will develop, it is crucial to require all those who commence treatment to complete their therapy. To ensure the completion of treatment, special attention must be paid to the needs of the homeless, drug users, and those with psychiatric impairments. In addition, all tuberculosis patients should begin their posthospital care under direct observation. Patients who fail to complete treatment despite efforts to encourage and facilitate their cooperation should be subject to confinement after a hearing with full due process protections. PMID- 8484444 TI - Forging the future: the public health imperative. AB - During the 1980s, national policy promoted military expenditures and downsized domestic programs. These priorities, along with tax reform and deregulation, created a "domestic gulf crisis" with a new wave of vulnerable populations--poor children, the homeless, the elderly, and the uninsured. Our lack of a national health program compounds the problem. The 1990s will be a decade of change and challenge. To forge a healthier and stronger future for our nation, we must implement five public health imperatives: (1) We must have a national health program that is universal, comprehensive, and prevention-oriented, with built-in assurances for quality, efficiency, and a strong public health infrastructure. (2) We must have a comprehensive national health education and promotion program for all schoolchildren. (3) Women must have freedom of choice. (4) Prevention and public health must become one of our country's highest health priorities. (5) The federal government must increase its leadership, commitments, and resources to reach the goals set forth in Healthy Communities 2000 and Healthy People 2000. PMID- 8484445 TI - Automobile driver fatalities in frontal impacts: air bags compared with manual belts. AB - OBJECTIVES: The effectiveness of air bags was estimated in this study by comparing driver fatalities in frontal crashes with driver fatalities in nonfrontal crashes, for cars with air bags and manual belts and cars with manual belts only. METHODS: Fatal Accident Reporting System data for drivers fatally injured during 1985 to 1991 in 1985 to 1991 model year cars that were equipped with air bags in or before model year 1991 were analyzed. RESULTS: Driver fatalities in frontal crashes in air bag cars were 28% lower than those in comparable cars with manual belts only. This percentage was used for estimating the overall fatality reduction in air bag cars. The reduction was greater in large cars (50%) than in midsize cars (19%) or in small cars (14%). Air bags reduced driver fatalities in frontal crashes involving ejection by about 9%. Fatalities in frontal crashes among drivers who were reportedly using manual belts at the time of the crash were reduced by about 15%. The comparable reduction among drivers who were reportedly not using manual belts was 31%. CONCLUSION: It was estimated that air bags reduced the total number of all driver fatalities by about 19%. PMID- 8484446 TI - Bicycle helmet laws and educational campaigns: an evaluation of strategies to increase children's helmet use. AB - OBJECTIVES: The passage of a mandatory bicycle helmet law for children in Howard County, Maryland, provided an opportunity to compare legislation and education as strategies to increase helmet use. METHODS: In 1991, a survey was mailed to fourth-, seventh-, and ninth-grade students attending a stratified sample of public schools in Howard County and in two similar suburban/rural counties without helmet laws. RESULTS: Of 7217 students surveyed, 3494 responded (48.4%). Self-reported helmet use in Howard County rose from 11% to 37% after the law and accompanying educational campaign went into effect. Helmet use changed from 8% to 13% in Montgomery County, where educational efforts were undertaken, and from 7% to 11% in Baltimore County, where helmet promotion activities were minimal. Predictors of helmet use included having friends who wore helmets, believing helmet laws are good, being in fourth grade, living in Howard County, and using seatbelts regularly. CONCLUSIONS: Legislation combined with education appears to increase bicycle helmet use substantially more than does education alone. The Howard County law may be considered a successful model of a strategy to increase children's helmet use. PMID- 8484447 TI - An injury prevention program in an urban African-American community. AB - OBJECTIVES: Injury is a major US public health problem, particularly in urban minority communities. This paper evaluates the impact of the Safe Block Project, a comprehensive injury prevention trial, on home hazards and injury prevention knowledge in a poor urban African-American community. METHODS: Nine census tracts in the community were allocated to either the intervention area or the control area. The intervention, carried out by trained community outreach workers, consisted of (1) home modification for simple prevention measures, (2) home inspection accompanied by information about home hazards, and (3) education about selected injury prevention practices. Approximately 12 months after the intervention, random samples of control and intervention homes were assessed for home hazards and injury prevention knowledge. RESULTS: A significantly larger proportion of intervention homes than control homes had functioning smoke detectors, syrup of ipecac, safely stored medications, and reduced electrical and tripping hazards. No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct. CONCLUSIONS: There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct. The Safe Block Project could serve as a model for future urban injury prevention efforts. PMID- 8484448 TI - Racial misclassification of American Indians: its effect on injury rates in Oregon, 1989 through 1990. AB - OBJECTIVES: We assessed the extent to which injury rates among American Indians in Oregon are underestimated owing to misclassification of race in a surveillance system. METHODS: The Oregon Injury Registry, a population-based surveillance system, was linked with the Indian Health Service patient registration file from Oregon, and injury rates for American Indians were calculated before and after correcting for racial misclassification. RESULTS: In 1989 and 1990, 301 persons in the Oregon registry were coded as American Indian. An additional 89 injured persons who were coded as a race other than American Indian in the registry were listed as American Indian in the Indian Health Service records. The age-adjusted annual injury rate for health service-registered American Indians was 6.9/1000, 68% higher than the rate calculated before data linkage. American Indian ancestry, female sex, and residence in metropolitan counties were associated with a higher likelihood of concordant racial classification in both data sets. CONCLUSION: Injury rates among American Indians in an Oregon surveillance system are substantially underestimated owing to racial misclassification. Linkage of disease registries and vital records with Indian Health Service records in other states may improve health-related data regarding American Indians. PMID- 8484449 TI - Occupational injury deaths in Alaska's fishing industry, 1980 through 1988. AB - OBJECTIVES: Studies from other countries have identified fishing as a hazardous industry, but little is known about occupational injury mortality related to fishing in the United States. Alaska was chosen for this study because approximately 45,000 people annually participate in Alaska's fishing industry and fishing is thought to be a major contributor to occupational injury mortality in the state. METHODS: Work-related injury deaths in Alaska's fishing industry were identified by means of death certificates and US Coast Guard mortality data. Fatality rates were calculated by using average annual fishing industry employment estimates. RESULTS: The 5-year average annual fishing-related fatality rate was 414.6 per 100,000 fishermen. The majority of the decedents were Caucasian men who drowned while fishing. CONCLUSIONS: This study emphasizes that fishing is a dangerous industry in Alaska and demonstrates the benefit of using multiple data sources to identify fishing-related deaths in the state. PMID- 8484450 TI - The fluoridation of drinking water and hip fracture hospitalization rates in two Canadian communities. AB - OBJECTIVES: The purpose of this study was to compare hip fracture hospitalization rates between a fluoridated and a non-fluoridated community in Alberta, Canada: Edmonton, which has had fluoridated drinking water since 1967, and Calgary, which considered fluoridation in 1991 but is currently revising this decision. METHODS: Case subjects were all individuals aged 45 years or older residing in Edmonton or Calgary who were admitted to hospitals in Alberta between January 1, 1981, and December 31, 1987, and who had a discharge diagnosis of hip fracture. Edmonton rates were compared with Calgary rates, with adjustment for age and sex using the Edmonton population as a standard. RESULTS: The hip fracture hospitalization rate for Edmonton from 1981 through 1987 was 2.77 per 1000 person-years. The age-sex standardized rate for Calgary was 2.78 per 1000 person-years. No statistically significant difference was observed in the overall rate, and only minor differences were observed within age and sex subgroups, with the Edmonton rates being higher in males. CONCLUSIONS: These findings suggest that fluoridation of drinking water has no impact, neither beneficial nor deleterious, on the risk of hip fracture. PMID- 8484451 TI - Hip fracture rates in Hong Kong and the United States, 1988 through 1989. AB - OBJECTIVES: Prior studies have suggested that hip fracture rates are substantially lower in Asian countries than in the United States. However, comparisons have been limited by unavailability of recent data, differences in case definition, lack of data from similar time periods, and small sample sizes. This study sought to examine trends by age and sex, with separate statistics for those aged 85 or older. METHODS: Hospital discharge data were used to obtain hip fracture incidence in Hong Kong and the United States from 1988 through 1989. RESULTS: Within each population, women had higher hip fracture rates than men. Fracture rates in the United States were significantly higher for both sexes than rates in Hong Kong. For persons over the age of 80, rates of hip fracture among White US males exceeded those for Hong Kong women. Inclusion of transferred cases in hip fracture rates minimized differences between the countries. CONCLUSIONS: Despite increasing hip fracture rates in Hong Kong, those rates are still substantially lower than the rates in the United States. Identifying factors responsible for this variation may prove useful in the search for preventive strategies. PMID- 8484452 TI - Factors affecting gay and bisexual men's decisions and intentions to seek HIV testing. AB - OBJECTIVES: This paper describes the relationships of sociodemographic, attitudinal, and behavioral variables to (1) decision to be tested, (2) expressed intention to be tested, and (3) reasons for not being tested for the human immunodeficiency virus (HIV) antibody. METHODS: A sample of 1295 men completed an anonymous questionnaire in gay-identified venues. Factor analysis was used to group reasons for not being tested and logistic and multiple linear regression were used to model the dependent variables. RESULTS: Fifty-three percent of the respondents had been tested, of whom 26% tested positive. Metropolitan residence and anal intercourse most strongly correlated with previous test-seeking. Previous test experience correlated most strongly with intention to be tested. Reasons for not being tested fell into three groups: (1) desire for anonymity, (2) self-perceived health, and (3) no benefit and denial. The odds were lower for gay men than bisexuals and men who did not participate in anal intercourse to express a desire for anonymity. CONCLUSIONS: Public health agencies should be prepared to individualize testing policies and education to deal with specific concerns and fears. Improving access to the test by removing some of the current psychological and physical barriers will enhance its medical and public health value. PMID- 8484453 TI - Pregnancy and contraception use among urban Rwandan women after HIV testing and counseling. AB - OBJECTIVES: This study examined hormonal contraceptive use and pregnancy in urban Rwandan women, following human immunodeficiency virus (HIV) antibody testing and counseling. METHODS: A sample of 1458 childbearing urban Rwandan women aged 18 to 35 years was tested and followed for 2 years. RESULTS: At enrollment, 17% of 998 HIV-negative women and 11% of 460 HIV-positive women were pregnant, and 17% vs 23%, respectively, were using hormonal contraceptives. One year later, half of the HIV-positive and one third of the HIV-negative hormonal-contraceptive users had discontinued use. The 2-year incidence of pregnancy was 43% in HIV-positive and 58% in HIV-negative women. HIV-positive women with fewer than four children were more likely to become pregnant than those with four or more; this association persisted in multivariate analyses but was not noted among HIV negative women. At the end of the study, over 40% of non-users said that they would use hormonal contraception if it was provided at the study clinic, but 40% of HIV-positive women desired more children. CONCLUSIONS: Research is needed to identify the practical and psychosocial obstacles to effective long-term contraception among HIV-positive women. HIV counseling programs must specifically address the issue of childbearing. PMID- 8484454 TI - Treatment for glaucoma: adherence by the elderly. AB - OBJECTIVES: The purpose of this study was to determine the extent of nonadherence to treatment for glaucoma among elderly patients. METHODS: This was a retrospective cohort study of 2440 patients older than age 65 who were enrolled in the New Jersey Medicaid Program and who were newly initiated on a topical agent for the treatment of glaucoma. Two patient-specific measures of nonadherence were employed: (1) no filled prescription for any glaucoma medication over a 12-month period after the initiation of therapy and (2) number of days without therapy for glaucoma during this 12-month period. RESULTS: By the first measure, 569 patients (23%) were found to be nonadherent. The mean number of days without therapy during the study year was 112. Factors associated with nonadherence included the use of glaucoma medication requiring more than 2 administrations per day and the presence of multiple other medications in the patient's drug regimen. Patients started on multiple glaucoma medication were more adherent than those started on a single agent. Age and sex were not found to be predictors of nonadherence. CONCLUSIONS: Substantial nonadherence was found to be common in this population. More attention to the issue of nonadherence could result in important benefits in the preservation of sight. PMID- 8484455 TI - Potential health benefits of nutrition label changes. AB - OBJECTIVES: The Nutrition Labeling and Education Act of 1990 mandates the Food and Drug Administration to promulgate changes in nutrition labeling regulations. This study investigates the potential health benefits associated with expected changes in food consumption resulting from the act. METHODS: This paper provides four estimates of the potential health benefits from the dietary changes expected to occur as a result of the 1990 act. The upper bound estimates begin with the premise that all consumers will adopt the daily reference values of total fat, saturated fat, and cholesterol. The lower bound estimate is based on consumers' responses to a shelf-labeling program sponsored by the Food and Drug Administration in the 1980s. A computer model developed by Dr. Warren Browner and his associates was used to estimate the health benefits from reduced nutrient intakes. RESULTS: Estimates of the number of discounted life-years gained nationwide for the first 20 years after the implementation of the act range from a high of 1.2 million to a low of 40,000. CONCLUSIONS: The results of the study highlight that relatively small changes in nutrient intakes may generate large public health benefits. PMID- 8484456 TI - Race/ethnicity patterns in the homicide of children in Los Angeles, 1980 through 1989. AB - This study investigated age, sex, and race/ethnicity risk patterns for homicide based on 246 children (newborn to 14 years old) who were murdered in the city of Los Angeles 1980 through 1989. Rates of homicide are higher for newborn to 4-year olds than for 5- to 14-year-olds. Boys and girls have similar rates of homicide at young ages; among 5- to 14-year-olds, however, boys have higher rates. Characteristics of the victim, suspect, and event were fairly consistent across victim race/ethnicity. Rates vary by the victim's race/ethnicity; paralleling patterns among adults, rates of homicide are lowest for non-Hispanic White, higher for Hispanic, and highest for Black children. PMID- 8484457 TI - Bicycle helmet counseling by pediatricians: a random national survey. AB - A random sample of 1201 pediatricians who are members of the American Academy of Pediatrics completed questionnaires regarding bicycle injury prevention counseling. Of the 871 pediatricians in the sample who provide health supervision, 80% reported that they discuss bicycle helmet use with their patients at least once before the patient reaches the age of 12 years. Provision of bicycle helmet counseling did not vary significantly by pediatricians' age, gender, or practice location. The most important predictor of provision of bicycle helmet counseling was professional experience with injured children, including having had a patient who experienced a serious injury or death due to a bicycle accident in the last year. PMID- 8484458 TI - The risk of childhood injury on Boston's playground equipment and surfaces. AB - The Childhood Injury Prevention Program of the Boston Department of Health and Hospitals conducted a survey of injury risk in Boston's playgrounds. A standardized checklist was used to assess a 25% sample of public playgrounds for hazards. Climbers accounted for 34% of the hazards observed and had the greatest proportion of significant hazards. The surfacing material in 100% of the playgrounds observed was unsafe. Urban children risk exposure to hazardous playground equipment frequently situated above unsafe surfacing material. PMID- 8484459 TI - Surface-specific fall injury rates on Utah school playgrounds. AB - The purpose of this study was to estimate surface-specific rates of fall injuries on school playgrounds. Playground injuries related to falls from climbing equipment and the surfaces involved were identified from injury reports for 1988 to 1990 from 157 Utah elementary schools. Enrollment data and playground inspections were used to estimate student-years spent over each surface. The fall injury rates per 10,000 student-years were asphalt, 44; grass, 12; mats, 16; gravel, 15; and sand, 7. These data did not show that impact-absorbing surfaces reduce fall injuries on playgrounds better than grass. Improved field studies are needed to guide policy decisions for playground surfacing. PMID- 8484460 TI - A proposed classification code for farm and agricultural injuries. AB - A fundamental problem with classifying agriculturally related injury is that there is neither a rational nor a comprehensive scheme for grouping incidents into categories describing actual exposures encountered on farms and in agricultural work. Current surveillance systems are unable to differentiate between work that is related to farm production and work that is not, and to include all exposed persons in the surveillance. The proposed Farm and Agricultural Injury Classification Code is a step toward overcoming these problems. When it was applied to previously analyzed fatality data, 40% of cases previously identified as farm production work were reclassified into other categories. PMID- 8484461 TI - Occupational and environmental exposures reported to poison centers. AB - This analysis of 25,368 occupational and 7,565 environmental exposure cases characterizes the occupational and environmental exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System. Compared with other poisonings, occupational and environmental exposures were predominantly inhalation exposures rather than ingestions, were more often subacute or chronic, and demonstrated greater morbidity, mortality, and increased use of health care resources. As regional poison centers evolve to fill a critical information void in the management and assessment of environmental and occupational exposures, the American Association of Poison Control Centers Toxic Exposure Surveillance System provides an important, untapped passive surveillance mechanism. PMID- 8484462 TI - Hip fracture incidence before and after the fluoridation of the public water supply, Rochester, Minnesota. AB - Recent ecological comparison studies have suggested a positive association between fluoridation and hip fracture. Using data from the Rochester Epidemiology Project, we found the incidence of hip fracture for the 10 years before the fluoridation of the Rochester, Minn, public water supply was 484 per 100,000, compared with 450 per 100,000 in the following 10 years. When the effects of calendar time and age were controlled for, the relative risk associated with fluoridation was 0.63. These ecologic trend data suggest that the fluoridation of public water supplies is not associated with an immediate increase in rates of hip fracture. Further studies of this association at the individual level are clearly required before public policy decisions can be made. PMID- 8484463 TI - Antidepressants and falls among elderly people in long-term care. AB - All eligible residents of a long-term care facility (488 women and 147 men with a 6-month minimum stay) were prospectively followed for 1 month for the development of falls. Use of psychotropic medications (excluding as needed prescriptions), functional status, and a history of falls were assessed at the start of the study month. Results of analyses using logistic modeling procedures suggest that institutionalized women on antidepressants may have an increased risk of falling, regardless of fall history, functional status, or age. A relationship between antidepressants and falls was not found for men. These results may help target high-risk individuals for future preventive efforts. PMID- 8484464 TI - Anergy compromises screening for tuberculosis in high-risk populations. AB - Anergy may occur in groups at high risk for tuberculosis, compromising tuberculin skin testing. Within New York City's correctional system, anergy prevalence was 25% among opiate users referred to detoxification programs and 3% in the general population. Correlates of anergy were recent weight loss and needle sharing. The high prevalence of anergy among opiate users compromises the utility of tuberculosis screening and suggests the need for routine chest x-rays to detect pulmonary tuberculosis in some high-risk-populations. PMID- 8484465 TI - Local health officers' views on hazardous waste remediation. AB - Hazardous waste sites are a priority for local health officers in New Jersey. However, most officers feel that they are not adequately briefed or consulted by federal and state officials who manage site remediation. Consequently, many local health officers tend to be neutral or negative about federal and state site remediation plans. Consultation with local health officers should be formally built into the site remediation process, and officers should directly approach their state governments to gain access. PMID- 8484466 TI - Continuing female predominance in depressive illness. AB - This paper examines gender differences in temporal trends for major depressive disorder in childhood, adolescence, and young adulthood. The study sample, a high risk group from the National Institute of Mental Health Collaborative Study on the Psychobiology of Depression, includes 2000 first-degree relatives of probands with affective disorder. The age-specific incidence rates were analyzed to determine the effect of gender, age, period, and cohort on depression by age 35. Women had nearly a twofold increase in risk of major depressive disorder, with rates peaking between adolescence and early adulthood. Vulnerability to depression was highest in the 1960s and 1970s. The rate increase in recent decades has not corresponded to a reduction in the gender differences. PMID- 8484467 TI - New York City's tuberculosis control efforts: the historical limitations of the "war on consumption". AB - New York City began America's first campaign to control tuberculosis in 1893, and the disease declined until the 1970s. Throughout the 20th century, New York relied on three control strategies: screening, supervised therapy, and detention of noncompliant persons. Officials consistently identified the persistent foci of tuberculosis to be minorities and the poor, and they concentrated efforts among these populations. Recently, however, in the setting of rising human immunodeficiency virus infection and homelessness, tuberculosis--including multidrug-resistant strains--has returned to New York with a vengeance. Tuberculosis control in the city has been limited by two problems that hamper many public health programs: (1) antituberculosis measures, while appropriately targeting the poor, have been inconsistently funded and poorly coordinated; and (2) efforts have emphasized detection and treatment of individual cases rather than improvement of underlying social conditions. Renewed efforts by New York and other cities must address these limitations. PMID- 8484468 TI - Commentary: tuberculosis in New York City--the consequences and lessons of failure. AB - The resurgent tuberculosis epidemic represents--especially in New York City--a failure to maintain a public health infrastructure that was focused on preventing active disease in high-risk populations (i.e., individuals with the human immunodeficiency virus [HIV]) and on treating active tuberculosis patients until cured. Although the tuberculosis problem in New York City and other localities is worsened by homelessness, poverty, and substance abuse, it is possible to bring tuberculosis under control by directing public health resources into targeted programs that enhance compliance with tuberculosis treatment regimen and expand chemoprophylaxis efforts among HIV-infected individuals. These two avenues will decrease, respectively, the number of cases of multidrug-resistant tuberculosis and the total number of new cases. PMID- 8484469 TI - The validity of Medicaid diagnoses of hip fracture. PMID- 8484470 TI - Handedness, traffic crashes, and defensive reflexes: an indirect test. PMID- 8484471 TI - Potential bias in cardiovascular risk behavior study. PMID- 8484472 TI - The origins of infant salmonellosis. PMID- 8484473 TI - Accuracy of an automatic impedance apparatus in a population with secretory otitis media: principles in the evaluation of tympanometrical findings. AB - INTRODUCTION: The primary demand for a screening procedure for secretory otitis media (SOM) is to identify an objective test with sufficient sensitivity and specificity to meet the needs of the screening program. This study was designed to estimate the value of a portable automatic impedance apparatus to meet these needs. SUBJECTS AND METHODS: Two hundred twenty children with unilateral or bilateral SOM were evaluated in a double-blind, cross-sectional study. All have fulfilled two of the following three criteria for surgical intervention: (1) SOM by physical examination, (2) greater than 20 dB hearing impairment, and/or (3) adenoid symptoms. All ears were evaluated using tympanometry, following which myringotomy was performed. RESULTS: Otomicroscopy showed fluid behind the tympanic membrane in 393 ears. All underwent myringotomy. Thirteen percent (51 ears) were empty. Of the otomicroscopic findings consistent with SOM, 82% had B curves, 6% had C2 curves, 8% had C1 curves, and 4% had A curves. Both C2 and B curves were considered abnormal. Sensitivity of the apparatus is 94.4% and of the specificity is 52.9%. There was no statistical correlation between tympanometrical findings and fluid viscosity. RESULTS: A test intended for screening has to be simple, easy, and quick to perform. Furthermore, the test should have high sensitivity. The automatic impedance apparatus is able to meet these demands; however, the individual results have to be confirmed by another method, eg, otomicroscopy, pure-tone audiometry, and/or manual tympanometry. PMID- 8484474 TI - Change of bone conduction thresholds by total footplate stapedectomy in relation to age. AB - INTRODUCTION: The influence of age on threshold changes of bone conduction after stapedectomy has not been thoroughly studied. Improvement of the Carhart notch by stapes surgery might be related to age as well as an increase in cochlear sensitivity to surgical trauma. PATIENTS AND METHODS: A retrospective study on the outcome of stapedectomy was undertaken. The results of surgery performed on 387 ears in 315 patients for otosclerosis between 1962 and 1989 were obtained. Stapedectomy, performed by a single surgeon, consisted of total stapedectomy, seal of the oval window with tragal perichondrium, and insertion of a free tragal cartilage graft. RESULTS: Analysis of bone conduction changes with stapedectomy shows an average improvement of 5 to 6 dB at 0.5, 1, and 2 kHz with best improvement at 2 kHz. At 4 kHz a mean decrease of 4 dB is recognized. The improvement of bone conduction at 2 kHz is 12 dB in patients younger than 30 years compared with 4 dB in patients older than 60 years (P < .05). The youngest group was improved by 2 dB at 4 kHz, whereas the oldest group deteriorated by 5 dB (P < .05). Age relationship was apparent in all 4 frequencies. CONCLUSIONS: With increasing age there is less improvement in bone conduction at 0.5, 1, and 2 kHz with correction of the Carhart notch and more deterioration at 4 kHz. The cochlear sensitivity to surgical trauma increases with age. In younger patients the preoperative bone conduction levels do not reflect the true cochlear reserve. Patients younger than 40 years of age might profit more from a partial or total footplate removal in stapedectomy, as this better corrects the Carhart notch. Patients older than 40 years of age might profit from a stapedotomy as this better preserves high frequencies. PMID- 8484475 TI - Surgical approach to pyriform sinus fistula. AB - INTRODUCTION: Congenital pyriform sinus fistula is recognized as a potential cause of recurrent cervical inflammation, recurrent abscess, and acute suppurative thyroiditis. Failure to recognize this diagnosis may result in recurrence following administration of antibiotics and incision and drainage. This study reflects the authors' experience in treating four patients with this diagnosis. MATERIALS AND METHODS: Patients included three children and one adult ranging in age from 7 to 34 years. The steps necessary to confirm the diagnosis and the subsequent surgical treatment are reviewed. RESULTS: All fistula occurred on the left side. In each case the fistula originated in the apex of the pyriform sinus. It subsequently penetrated the inferior constrictor in three cases and the thyroid cartilage in one to end in the thyroid gland or perithyroid tissue. The opening of the pyriform sinus fistula could be identified by either barium swallow or direct endoscopy. Complete fistulectomy resulted in resolution of symptoms in all cases. CONCLUSION: Pyriform sinus fistula is a rare entity. It may be of fourth branchial pouch origin. Identification of the fistula opening in the pyriform sinus may be difficult or impossible during acute inflammation because of edema. The authors advocate the fistula be exposed through incision of the inferior constrictor muscle, which facilitates total removal. Resection of the fistula, adjacent scar tissue, and a portion of the thyroid gland when the fistula is attached, should be regarded as essential steps in curing this entity. PMID- 8484476 TI - Results of curative laser microsurgery of laryngeal carcinomas. AB - INTRODUCTION: Between 1979 and 1991 the author treated more than 1,200 patients with malignant tumors of the upper-aerodigestive tract transorally using laser microsurgery with curative, palliative, or symptomatic intention. PATIENTS AND METHODS: This report is based on 240 patients without prior treatment, treated between 1979 and 1985 with curative intention for cancer of larynx (pTis-pT4 (p)N0-pN2c). Patients with simultaneous second primaries and/or distant metastases were excluded. Neck metastases of the category N3 (UICC 1987) were not found in the group. Patients were divided into two groups. Group A (n = 159) includes glottic cancer as follows: Tis, 29; T1, 96; T2 (small, vocal cord mobile), 34. All patients were treated by laser microsurgery. There were only 6% local recurrences with one patient needing total laryngectomy. The overall 5-year survival rate (Kaplan-Meier) was 86.5%. The adjusted 5-year survival rate was 100%. The group B patients (n = 81) included 30 supraglottic patients. Fifty eight patients were in tumor category pT2, among them there were 38 with glottic cancer (so called T2b, with vocal cord mobility impaired). Seventeen patients had pT3 and 6 pT4 tumors. RESULTS: Treatment consisted of laser microsurgery plus/minus neck dissection (23/81 = 28%) (mainly regionally limited functional surgery, only four radical neck dissections) plus/minus postoperative radiotherapy (29/81 = 35%). There were 22% local recurrences with six patients requiring total laryngectomy. The overall 5-year survival rate (Kaplan-Meier) was 59%. DISCUSSION: This study confirms the usefulness of laser microsurgery for laryngeal carcinoma. Surgery is individualized and adapted to the size of the tumor. Multiinstitutional studies are needed to compare laser microsurgery with radiation therapy. PMID- 8484477 TI - Prognostic factors in glottic carcinoma clinical stage I and II treated by surgery or radiotherapy. AB - INTRODUCTION: Decision making regarding selection of treatment for early glottic carcinoma remains controversial. This study was undertaken to assess the impact of such factors as patient age, stage of tumor, site and size of characteristic of the lesion, and other characteristics relative to disease free and overall survival rates. PATIENTS AND METHODS: The records of 145 consecutive patients with stage I and II glottic carcinomas treated between 1954 and 1990 were reviewed retrospectively. Surgery was performed on 50 patients (34.5%), and irradiation therapy was performed on 95 (65.5%). Cox's regression model was used to estimate the hazard ratios of recurrence and death. RESULTS: Median follow-up was 69.3 months. Death due to cancer or treatment complications occurred in 29 patients, whereas 25 patients died due to causes not related to cancer. Five-year rates for overall survival and disease-free intervals were 94.6% and 70.8%, respectively. Tumor control was achieved by initial surgery or irradiation in 78% and 69.5%, respectively. T stage and vocal cord mobility in this series were not associated with prognosis. Arytenoid involvement intended to indicate a worse prognosis. Other site involvement such as anterior commissure had no prognostic impact. DISCUSSION: Although stage I and II glottic cancers represent a heterogenous group, survival rates after surgery or radiotherapy vary relatively little. Death due to occurred in 17.9% of patients included in this series, whereas 17.2% died due to causes not related to cancer. Local recurrence following irradiation (29.5%) occurred more frequently than following surgery (10%). The choice of treatment modality for stage I and II glottic cancer should be justified by patient preference, involvement of anterior commissure, and impairment of vocal cord mobility and should not be a contraindication to radiotherapy. PMID- 8484478 TI - Extramedullary plasmacytoma of the larynx. PMID- 8484479 TI - Acquired laryngomalacia secondary to obstructive adenotonsillar hypertrophy. PMID- 8484480 TI - Osteogenesis imperfecta. PMID- 8484481 TI - Possible autocrine growth stimulation of cholesteatoma epithelium by transforming growth factor alpha. AB - INTRODUCTION: Transforming growth factor alpha (TGF-alpha) is known to be produced by normal human keratinocytes and to stimulate their proliferation. The squamous epithelium of middle ear cholesteatoma is believed to exhibit hyperproliferative characteristics. This study was undertaken to determine if growth factors can be identified in cholesteatoma. MATERIALS AND METHODS: Cholesteatoma samples (n = 6) and retroauricular skin (n = 9) were obtained during surgery. Monoclonal antibody against epidermal growth factor (EGF) and TGF alpha were evaluated in these specimens using immunohistochemical techniques. RESULTS: Epidermal growth factor receptor (EGF-R) was highly expressed in the basal layer of the epidermis, hair follicles, eccrine sweat glands, and the capillary system of normal skin. In the majority of cholesteatoma samples, expression of EGF-R was not confined to the basal layer but persisted in suprabasal cells of the stratum spinosum and stratum granulosum. In two cases, heterogenous standing was found in different parts of the same cryosection. Staining for TGF-alpha was consistently stronger in cholesteatoma than in normal skin, and encompassed all epithelial cell layers. Immune cells infiltrating the stroma of cholesteatoma stained positively for TGF-alpha. CONCLUSION: These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF-alpha contributing to its unrestrained growth in the middle ear cavity. PMID- 8484482 TI - Current national trends in the posttreatment follow-up of patients with squamous cell carcinoma of the head and neck. AB - INTRODUCTION: Follow-up of individuals treated for a primary squamous carcinoma of the upper aerodigestive tract is critical because of the high risk of development of either recurrent disease or a new primary tumor. A mail survey of physicians actively practicing head and neck surgery was undertaken. MATERIALS AND METHODS: A multiple-choice survey was distributed to 400 members of the American Society for Head and Neck Surgery. Respondents indicated approach to post-treatment follow up. RESULTS: Surveys were returned from 290 members (73%). Routine monthly follow up is advocated by 73% of respondents during the first postoperative year. Patients are followed every 2 to 3 months in the second postoperative year by 90% of respondents. During postoperative years, 3 to 5 patients are seen every 4 to 6 months by 97% of respondents. All respondents see patients either semiannually or annually for the remainder of their lives. Sixty percent of respondents advocate annual screening chest radiographs, whereas 14% do not order routine chest radiographs. The overwhelming majority of respondents reserve barium swallow and computed tomographic (CT) scans for evaluation of symptomatic patients. Similarly, nuclear imaging is reserved for patients with specific symptoms or abnormal laboratory tests. Blood tests most frequently monitored include complete blood cell count (CBC) (43%), thyroid function test (22%), and liver function test (20%). Follow-up endoscopic evaluation under anesthesia is reserved for symptomatic patients by over 95% of respondents. CONCLUSION: These data demonstrate that head and neck surgeons rarely use supplemental studies other than chest radiograph during routine follow up. The authors speculate that routine chest radiograph may be valuable in screening for a second primary carcinoma. Techniques to screen for esophageal tumors remain contentious. PMID- 8484483 TI - Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss. AB - INTRODUCTION: This study examines the incidence of vitamin B12 deficiency in three groups of noise-exposed subjects: patients with chronic tinnitus and noise induced hearing loss (NIHL), patients with NIHL only, and subjects demonstrating normal hearing. MATERIALS AND METHODS: A group of 113 army personnel exposed to military noise was studied. The mean age was 39 years. Chronic tinnitus and NIHL existed in 57 subjects. NIHL alone was observed in 29 subjects, and 27 subjects had normal audiograms. All subjects were queried about noise exposure and dietary habits. Vitamin B12 serum levels were measured. RESULTS: Patients with tinnitus and NIHL exhibited vitamin B12 deficiency in 47% of cases (blood levels < or = 250 pg/mL). This was significantly more (P < .023) compared with NIHL and normal subjects who exhibited vitamin B12 deficiency in 27% and 19%, respectively. CONCLUSION: These observations suggest a relationship between vitamin B12 deficiency and dysfunction of the auditory pathway. Some improvement in tinnitus and associated complaints were observed in 12 patients following vitamin B12 replacement therapy. The authors recommend that routine vitamin B12 serum levels be determined when evaluating patients for chronic tinnitus. PMID- 8484484 TI - [The value of the anamnesis and physical examination in surgical pathology of the thyroid gland. Report on 423 thyroidectomies]. AB - The purpose of this paper is to present a retrospective study of 423 cases of surgical pathology of the thyroid gland. All the cases underwent surgery during a period of 11 years. The data gained through these ways were statistically studied and compared with those provided by histological diagnosis, with the aim of searching any clinic situations that can lead to the suspicion of oncological pathology of the gland. PMID- 8484485 TI - [Kniest syndrome. An audiological study]. AB - In this syndrome there is a disproportionate dwarfism with kyphoscoliosis, stiffness of the joints, minor facial dysmorphia, myopia and both conductive and sensorineural deafness in 50 percent of patients. It is a dominant autosomic heritable malady of unknown incidence, but both sexes seems equally affected. The patient's condition is diagnosed at birth, because of the short limbs and the enlargement of the joints. In the presented case, diagnosed at birth, the deafness was suppose to be transmissive, owing to the coexistence of a cleft palate, and consequently a grommet was inserted in the tympanum. Only afterwards, when the girl was 12 years old, the cochlear component of the hypoacusis fell in consideration. PMID- 8484486 TI - [The value of the computer tomography (CT) and magnetic resonance (MR) in tumors of the ear]. AB - The first case report is an undifferentiated squamous cell carcinoma of the ear. This patient complained with pain and discharging ear, which led us to practice a TC followed by an attico-antrotomy. The pathologist could detect in the removed tissue the neoplasm in its early evolutive stages. In the other case the earache and the suppuration suggested at first a carcinoma. In spite of the TAC and MR exams the surgery that followed was not confirmative of the tumor presence. PMID- 8484487 TI - [Lateral isolated neurofibroma of the neck]. AB - The neurofibroma (NF) of the neck is a neurogenic tumor seldom presented. Sometimes solitary, as the case reported, or within the context of von Recklinghausen's disease. When diagnosis is doubtful either the TAC, the RMN of the PAAF show its usefulness. However the ultimate diagnosis is made through the histologic exam of the removed lump, which is the elective treatment. PMID- 8484488 TI - [Evaluation of the possible ototoxicity of josamycin by high frequency audiometry]. AB - Josamycin is an antibiotic macrolide similar to erythromycin, with some differences in its biologic behaviour. There have been no reports of ototoxic effects caused by this drug, but its similitudes with erythromycin have prompted us to undertake a study about its possible cochleo-toxicity. Most trials of this kind have been carried out using conventional audiometry (up to 8,000 Hz), thus not being able to detect threshold shifts above this frequency. Ototoxic lesions usually begin in the upper frequency limit. Twenty-eight patients without previous auditory impairment were studied with conventional (up to 8,000 Hz) and high-frequency audiometry (up to 20,000 Hz) before and after oral treatment with josamycin during eight days. No significant differences were found in auditory thresholds registered before and after treatment in any of the patients. These results suggest that josamycin is devoid of any cochleo-toxic effect in all the frequencies that a normal subject can hear. PMID- 8484489 TI - [Myringoplasty. . 5-year study on the anatomic and functional results]. AB - The AA. consider both anatomical and functional results with the "on-lay" procedure for closure of central tympanic perforations in 131 cases, treated at their Department in a 5 years term. They report the end conditions pointing out several parameters implicated as type and size of the perforation, anesthetic used, source of the graft and surgical approach. Finally they confront the anatomical and the functional results. The aim of the paper is to emphasize the value of the procedure followed in the attempt of re-stablishing the integrity of the ear drum. PMID- 8484490 TI - [Complications of phonatory fistuloplasty. Case report]. AB - The paper deals with a severe mediastinal complication when performing, in a laryngectomee, a secondary fistuloplasty. Brief review of possible failures of this surgery, which are not common, but sometimes can be severe and even deadly. PMID- 8484492 TI - Historical overview: comparison of nursing research classification systems. PMID- 8484491 TI - [Laryngeal myoplasty. Cancer T2 T3]. AB - The possibility of autoplasties given for the sternohyoid muscle allows the step of reconstructive surgery in all cancers of the larynx. This possibility has been reasserted gradually during the elapsed years, and luckily there are updated methods, proved enough with a wide reach, regarding the physiology of the larynx, that is to say: swallowing, respiration and phonation. Our commitment in functional surgery has been accomplished under the clinical points of view and we have the pleasure to inform with this historical synthesis of those procedures. PMID- 8484493 TI - Rethinking the typology of nursing research. PMID- 8484494 TI - Classification of nursing-related dissertations: genesis of a taxonomy of nursing's research knowledge. PMID- 8484495 TI - Sigma Theta Tau International's classification system for nursing research. PMID- 8484496 TI - The grassroots lobbying handbook: empowering nurses through legislative and political action. PMID- 8484497 TI - Nurse practitioners and certified nurse-midwives: a meta-analysis of studies on nurses in primary care roles. PMID- 8484498 TI - The safety of intravenous phentolamine administration in patients with neuropathic pain. AB - The safety of intravenous (i.v.) infusion of large doses of phentolamine as an outpatient diagnostic tool for sympathetically maintained pain was studied retrospectively in 100 consecutive patients (73 females and 27 males) with chronic pain. All patients were pretreated with i.v. fluids followed, in most cases, by propranolol, 1-2 mg i.v. (n = 95). Ten minutes later the phentolamine infusion commenced, lasting for 20 min. In 90 patients, the dose of phentolamine was 35 mg. Two patients received 25 mg, and 8 patients received larger doses of 50-75 mg. No major complications occurred during or after the test, and only small changes in arterial blood pressure or heart rate were observed. All patients developed mild nasal stuffiness, but no decline in oxygen saturation was observed. Five patients developed one of the following minor complications for a brief duration, that resolved spontaneously: sinus tachycardia, premature ventricular beats, dizziness, or wheezing. We conclude that i.v. phentolamine administration is safe in patients with neuropathic pain. PMID- 8484499 TI - Transcutaneous electrical nerve stimulation reduces the incidence of vomiting after hysterectomy. AB - The possible postoperative antiemetic effect of transcutaneous electrical nerve stimulation (TENS) on the P6 point (on the Pericardium Channel of Hand-Jueyin) was evaluated in 103 women undergoing hysterectomy. TENS on the P6 point was applied 30-45 min before induction of anesthesia in 51 patients and continued for 6 h postoperatively. The control group, 52 patients, was treated exactly in the same way but with the electrical stimulator turned off. Incidence of vomiting was assessed blindly 2 h, 4 h, 6 h, and 8 h postoperatively. The incidence of vomiting postoperatively was significantly less in the TENS-treated group when compared with the control group (between 0 h and 2 h: 23% vs 43%, P < 0.05; between 2 h and 4 h: 27% vs 50%, P < 0.025; and between 4 h and 6 h: 31% vs 67%, P < 0.001, respectively). Six hours postoperatively TENS was discontinued, and 8 h postoperatively the two groups did not differ significantly for incidence of vomiting (between 6 h and 8 h: 51% vs 65%). The authors conclude that TENS reduces the incidence of vomiting after hysterectomy. PMID- 8484500 TI - Density, specific gravity, and baricity of spinal anesthetic solutions at body temperature. AB - One of the most important physical properties affecting the level of analgesia achieved after intrathecal administration of a local anesthetic is its density relative to the density of the cerebrospinal fluid (CSF) at 37 degrees C. In this study, density, specific gravity, and baricity of local anesthetic solutions at body temperature were determined volumetrically to five significant figures. Standard solutions of 2% lidocaine, 0.5% and 0.75% bupivacaine, and 0.9% sodium chloride were tested. Bupivacaine, 0.75%-water dilutions and tetracaine, 0.2%, in water were also studied. The densities of all commercially prepared solutions were less than that of the normal range of CSF at 37 degrees C. The density of 0.2% tetracaine was the same as water. Continued dilution of 0.75% bupivacaine with water resulted in increasingly hypobaric solutions. However, only the 0.075% bupivacaine (1:9 dilution) solution had a density comparable to water. Knowledge of relative baricities aids in the selection of an appropriate local anesthetic for intrathecal use. PMID- 8484501 TI - Retrobulbar hemorrhage after 12,500 retrobulbar blocks. AB - To determine the incidence of hemorrhage after retrobulbar nerve block, 12,500 consecutive cases were reviewed. Fifty-five retrobulbar hemorrhages occurred after retrobulbar injection, a prevalence of 1 in 227 (0.44%). This compares favorably with the quoted prevalence of 1%-3% in the literature. Acquired vascular disease was a significant risk factor (P < 0.017). Surgery was postponed in 41 (75%) of the cases in which a hemorrhage developed. Although retrobulbar hemorrhage is considered a serious complication of retrobulbar anesthesia, the eventual visual outcome after surgery in these patients was not significantly different from the control group. PMID- 8484502 TI - Comparison of an ephedrine infusion with crystalloid administration for prevention of hypotension during spinal anesthesia. AB - This study was designed to compare the efficacy of an ephedrine infusion with crystalloid administration for reducing the incidence of hypotension during spinal anesthesia. Fifty-four ASA I patients scheduled for postpartum tubal ligations under spinal anesthesia were randomly allocated to receive either 15 mL/kg of crystalloid (crystalloid group) or an ephedrine infusion (infusion group). Spinal anesthesia was performed using 70-90 mg of hyperbaric 5% lidocaine. Patients in the infusion group immediately thereafter received an ephedrine infusion at a rate of 5 mg/min for the first 2 min and then 1 mg/min for the next 18 min. The incidence of hypotension was 15/27 (55%) in the crystalloid group and 6/27 (22%) in the infusion group (P < 0.05). There was no significant difference between the groups in relation to the level of anesthesia or maximal heart rate, and hypertension did not occur in either group. We conclude that a prophylactic ephedrine infusion is effective for minimizing and managing hypotension associated with spinal anesthesia and compares favorably with crystalloid administration in this patient population in terms of efficacy and incidence of side effects. PMID- 8484503 TI - Hemodilution induces stable changes in global cardiovascular and regional myocardial function. AB - The cardiovascular responses associated with isovolemic hemodilution have been described. However, the stability of these responses over time remains controversial. We hypothesized that the hemodynamic responses to isovolemic hemodilution are stable over time. Nine fentanyl-midazolam-anesthetized dogs were monitored to follow global cardiovascular and regional myocardial function. Isovolemic hemodilution was performed to a moderate (hemoglobin = 7.5 g%) target hemodilutional state that was maintained for 4 h. Data were obtained at each hemodilutional state and each hour during the 4-h period of sustained moderate hemodilution. During acute hemodilution, cardiac output increased from 2.6 +/- 0.5 L/min to 3.0 +/- 0.5 L/min (P < 0.05) and mean coronary flow increased from 20.8 +/- 2.4 mL/min to 31.4 +/- 5.5 mL/min (P < 0.05). Cardiac output and mean coronary flow remained elevated during the extended hemodilutional period. In addition, norepinephrine increased from 586 +/- 152 pg/mL to 1135 +/- 247 pg/mL (P < 0.05) during acute isovolemic hemodilution and remained at this increased level during extended hemodilution. Epinephrine levels did not change with hemodilution. Compensatory mechanisms such as increases in cardiac output and mean coronary flow observed during acute hemodilution persist during extended periods of hemodilution. PMID- 8484504 TI - Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance? AB - Alfentanil undergoes extensive hepatic metabolism and exhibits a high degree of interindividual variability in hepatic clearance. The purpose of this investigation was to determine the specific hepatic cytochrome P450 isozyme(s) that catalyzes alfentanil metabolism. Alfentanil metabolism by microsomes from rat and human livers was determined by using gas chromatography-mass spectrometry. Rat liver alfentanil oxidation was increased threefold by treatment with pregnenolone 16 alpha-carbonitrile, an inducer of cytochrome P450 3A, but not by treatment with phenobarbital, beta-naphthoflavone, or pyrazole (which induce P450s 2B, 1A, and 2E1, respectively). Human liver microsomal alfentanil metabolism was correlated strongly with the content of cytochrome P450 3A3/4 (r = 0.85, P < 0.005), measured by Western blot analysis with a rabbit anti-human P450 3A3/4 probe. Alfentanil metabolism was diminished by the P450 3A3/4 substrate and competitive inhibitor midazolam, and was abolished by the specific P450 3A3/4 inhibitor troleandomycin. No other selective inhibitor of P450 isozymes (P450s 1A2, 2A6, 2C9/10, 2D6, 2E1) diminished alfentanil metabolism. These results establish that human alfentanil metabolism is catalyzed predominantly, if not exclusively, by P450 3A3/4. Interindividual variability in human alfentanil disposition and alfentanil drug interactions may be attributable to individual differences in P450 3A3/4 activity. PMID- 8484505 TI - Effects of alfentanil on the hemodynamic and catecholamine response to tracheal intubation. AB - A randomized, placebo-controlled study was conducted in 60 ASA Class I, II, and III patients to determine the dose response of alfentanil in moderating the cardiovascular and catecholamine response to tracheal intubation (INT). Patients were randomly allocated into one of four groups to receive either 15 micrograms/kg alfentanil (A15), 30 micrograms/kg alfentanil (A30), 45 micrograms/kg alfentanil (A45), or normal saline (control), given intravenously (i.v.) before induction of anesthesia. One minute after administration of 4.0 mg/kg thiopental and 1.5 mg/kg succinylcholine i.v., tracheal intubation was performed using direct laryngoscopy. In response to INT, increases in heart rate, systolic blood pressure, and systemic vascular resistance occurred in the control group. These changes were significantly more than corresponding changes of heart rate, systolic blood pressure, and systemic vascular resistance in all three alfentanil groups (P < 0.05). In contrast, cardiac index and ejection fraction decreased moderately in every group during the study period, but there were no differences among groups with respect to either cardiac index or ejection fraction at corresponding times following INT. In the control group, epinephrine and norepinephrine serum concentrations increased by 152 +/- 52% and 58 +/- 62%, respectively, following INT (different from A30 and A45, P < 0.05). However, up to a dose of 30 micrograms/kg (A30), a dose-dependent decrease in the maximum percent changes of both epinephrine and norepinephrine occurred in response to INT. A larger dose of alfentanil was no more efficacious as the catecholamine response to tracheal intubation was not significantly different when comparing the A45 and A30 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484506 TI - Intranasal meperidine titration for postoperative pain relief. AB - A prospective, randomized, double-blind study investigating the efficacy of intranasal meperidine as compared with intravenous (i.v.) administration for postoperative pain relief is described. The study was limited to the initial titration of pain relief during a 2-h period immediately after surgery. Sixty women having undergone a hysterectomy were studied. Initially and when complaining of a pain intensity > or = 40 on the 101-point numerical rating scale (NRS), 30 patients received 6 sprays (27 mg) meperidine intranasally and simultaneously 6 mL NaCl 0.9% i.v. (nasal group); another 30 patients received 6 sprays of NaCl 0.9% intranasally and 6 mL of a diluted meperidine solution (27 mg) i.v. (intravenous group). Patients already having a pain reduction < 40 on the 101-point NRS, received half of the above dose. Meperidine was repeated every 5 min until the patients were pain free or refused further analgesic. Before the onset of meperidine titration and at 5- to 10-min intervals for 2 h thereafter, pain was evaluated with a 101-point NRS and a verbal rating scale. Within 20 and 35 min the pain scores evaluated by the NRS and verbal rating scale decreased in the intravenous and nasal group to a median of zero. The total dose of meperidine was 76.5 mg (range, 40.5-135.0) in the intravenous group and 104.4 mg (range, 27 135.0) in the nasal group (P < 0.05). One patient in each group showed a brief decrease in arterial hemoglobin oxygen saturation to < 90%. No patient complained of pain or burning in the nose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484507 TI - Inhibition of morphine-induced tolerance and dependence by a benzodiazepine receptor agonist midazolam in the rat. AB - We investigated whether midazolam administration influenced morphine-induced antinociception and tolerance and dependence in the rat. Antinociception was assessed by the tail-flick (TF) and the hot-plate test (HP 52 degrees C). Morphine tolerance developed after daily single injections of morphine for 11 days. The effect of midazolam on morphine-induced antinociception and tolerance was assessed by giving daily injections of various doses of midazolam for 11 days. The first injection of saline or midazolam was given intraperitoneally and 30 min later morphine (10 mg/kg body weight) was administered subcutaneously. Antinociception was monitored by measuring TF and HP latencies 60 min after the second injection. Midazolam was injected at four different concentrations: 0.03, 0.1, 0.3, and 3 mg/kg body weight. Chronic administration of morphine resulted in the development of tolerance to antinociception in both TF and HP tests, with rats exhibiting baseline antinociception on Day 9. Animals treated with midazolam alone showed little antinociception on Days 3-9. However, midazolam administration in morphine-treated animals attenuated morphine-induced tolerance to antinociception on Days 1-11 as measured by the tail-flick test. Midazolam also decreased the jumping behavior following naloxone injections in morphine dependent rats. These results suggest that midazolam may prolong the effects of morphine by delaying morphine-induced development of tolerance to antinociception. Midazolam also attenuated a decrease in weight gain induced by chronic injections of morphine. PMID- 8484508 TI - Effects of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy. AB - Ketorolac, a nonsteroidal anti-inflammatory drug, is alleged to produce postoperative analgesia without opioid-related side effects. Patients undergoing laparoscopic cholecystectomy were assigned randomly to receive either ketorolac or a placebo (saline) according to a double-blind protocol. Preoperative (baseline) pulmonary function was evaluated using a Respiradyne II monitor. Patients received midazolam, 2 mg, and 2 mL of either ketorolac, 60 mg (n = 31), or saline (n = 29), 20-40 min before surgery. Anesthesia consisted of thiopental, 4-5 mg/kg, and vecuronium, 0.1 mg/kg, for induction, and isoflurane, 0.5%-2.0%, with 67% nitrous oxide in oxygen for maintenance. A second 2-mL dose of the same study medication (ketorolac, 60 mg, or saline) was administered 4 h after the initial dose. Postoperatively, 66% of patients in the saline group complained of pain requiring treatment with fentanyl compared to 32% in the ketorolac group (P < 0.05). There were no significant differences between the two groups with respect to postoperative sedation, anxiety, pain, or nausea visual analog scores. Compared to the preoperative values, significant decreases in pulmonary function tests were noted in both groups at 4 h after the operation and the following morning (P < 0.01). In the ketorolac group, only values of forced expiratory volume at 1 s and forced expiratory flow at 25%-75% of the forced vital capacity at 4 h after the operation were significantly higher than those in the saline group (P < 0.05). Incidences of nausea (45% vs 52%) and vomiting (10% vs 10%) were similar in both groups. In conclusion, ketorolac decreased the postoperative requirement for opioid analgesic medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484509 TI - Hemodynamic changes during laparoscopic cholecystectomy. AB - Hemodynamics during laparoscopic cholecystectomy under general anesthesia (isoflurane in N2O/O2 (50%)) were investigated in 15 nonobese ASA Class I patients by using invasive hemodynamic monitoring including a flow-directed pulmonary artery catheter. During surgery, intraabdominal pressure was maintained automatically at 14 mm Hg by a CO2 insufflator, and minute ventilation was controlled and adjusted to avoid hypercapnia. Hemodynamics were measured before anesthesia, after the induction of anesthesia, after tilting into 10 degrees head up position, 5 min, 15 min, and 30 min after peritoneal insufflation, and 30 min after exsufflation. Induction of anesthesia decreased significantly mean arterial pressure and cardiac index (CI). Tilting the patient to the head-up position reduced cardiac preload and caused further reduction of CI. Peritoneal insufflation resulted in a significant increase (+/- 35%) of mean arterial pressure, a significant reduction (+/- 20%) of CI, and a significant increase of systemic (+/- 65%) and pulmonary (+/- 90%) vascular resistances. The combined effect of anesthesia, head-up tilt, and peritoneal insufflation produced a 50% decrease in CI. Administration of increasing concentrations of isoflurane, via its vasodilatory activity, may have partially blunted these hemodynamic changes. These results demonstrate that laparoscopy for cholecystectomy in head-up position results in significant hemodynamic changes in healthy patients, particularly at the induction of pneumoperitoneum. PMID- 8484510 TI - Pupillary response to noxious stimulation during isoflurane and propofol anesthesia. AB - We studied the effects of noxious stimuli on arterial blood pressure, heart rate, pupil size, and the pupillary light reflex in 13 volunteers anesthetized with either isoflurane or propofol. Those given isoflurane (n = 8) were anesthetized twice, in a randomly selected order, once at an end-tidal concentration of 0.8% and once at 1.2%. An intense noxious stimulus was provided by electrical stimulation applied to skin of the abdominal wall (65-70 mA, 100 Hz). Hemodynamic values and pupillary responses were recorded immediately before stimulation and at 15-60-s intervals during 8 subsequent min. In the volunteers given isoflurane (both concentrations), stimulation significantly increased pupil size (265 +/- 44%) and the amplitude of the light reflex (233 +/- 23%). In contrast, mean heart rate and systolic blood pressure increased only 19 +/- 7% and 13 +/- 7% after stimulation. Five additional volunteers were anesthetized twice with propofol (approximately 3 micrograms/mL plasma concentration) and 60% nitrous oxide. The same electrical stimulus was applied, and hemodynamic and pupillary measurements were obtained. During one propofol anesthetic, an esmolol infusion (100 micrograms.kg-1 x min-1) was started 10 min before stimulation to determine whether this agent would blunt the pupillary response. The pupillary light reflex increased more than 200% during both propofol anesthetics with or without esmolol; once again, heart rate and blood pressure changed little. We conclude that with these experimental conditions, the pupil is a more sensitive measure of noxious stimulation than the commonly used variables of arterial blood pressure and heart rate. PMID- 8484511 TI - Intrathecal acetylsalicylic acid and indomethacin are not analgesic for a supramaximal stimulus. AB - Intrathecal acetylsalicylic acid and indomethacin are analgesic for painful stimuli, and this has been demonstrated when the noxious stimuli are applied to normal and inflamed tissue. This study determined whether these drugs would alter the response to a supramaximal stimulus, e.g., tail-clamp. Rabbits were anesthetized with halothane and after arterial and venous cannulation, an intrathecal catheter was placed via a lumbar laminectomy. The minimum alveolar anesthetic concentration was then determined. Groups 1 (n = 8) and 2 (n = 6) received 0.5 mg/kg acetylsalicylic acid intrathecally and Group 3 (n = 7) 0.5 mg/kg indomethacin intrathecally. Group 4 (n = 8) did not undergo a laminectomy and received acetylsalicylic acid 25 mg/kg intraperitoneally. In addition, in Groups 2-4, before the surgical procedures, carrageenin 1 mg was injected into the tail to evoke an inflammatory response. Approximately 20 min after injection of the study drugs, minimum alveolar anesthetic concentration was determined again. In Groups 1-4, control minimum alveolar anesthetic concentration was 1.2 +/- 0.2%, 1.4 +/- 0.3%, 1.2 +/- 0.2%, and 1.5 +/- 0.1%, respectively; there was no statistically significant change in any group after injection of the study drugs. There were no temperature, hematocrit, or arterial blood pressure differences between groups or after injection of the study drugs. In this model intrathecal acetylsalicylic acid and indomethacin do not provide analgesia for a supramaximal stimulus. PMID- 8484512 TI - Canine tracheal blood flow after endotracheal tube cuff inflation during normotension and hypotension. AB - Tracheal tissue damage associated with endotracheal intubation may be a direct result of high mucosal contact pressure (MCP) generated by the endotracheal tube cuff. Tracheal blood flow (TBF) was measured at MCPs in the normotensive and hypotensive (mean arterial blood pressure, 50 mm Hg) canine model. Control TBFs through the individual rings in contact with the endotracheal tube cuff ranged between 26.6 +/- 2.7 and 44.5 +/- 5.0 with a mean of 35.0 +/- 2.5 mL.min-1 x 100 g-1 during normotension, and 15.0 +/- 4.9 and 22.5 +/- 5.0 with a mean of 18.9 +/ 0.9 mL.min-1 x 100 g-1 during hypotension. TBF was reduced significantly at all elevated MCPs in both groups. TBF also was measured during normotension and hypotension after cuff inflation to 15 mm Hg MCP at 1-h intervals for 3 h. TBF was reduced significantly from control to 14.9 +/- 1.5 mL.min-1 x 100 g-1 after 1 h during normotension, and continued to decline to 6.1 +/- 0.9 mL.min-1 x 100 g-1 after 3 h. During hypotension, TBF decreased significantly from control to 6.1 +/ 0.6 mL.min-1 x 100 g-1 at 1 h and remained unchanged at 3 h. These findings suggest that even at 20 mm Hg MCP, significant reductions in TBF may occur. For prolonged endotracheal intubation, especially during hypotension, significant reductions in TBF may occur at even lower MCP. PMID- 8484513 TI - Ventilation with nitrous oxide during open cholecystectomy increases the incidence of postoperative hypoxemia. AB - The effect of intraoperative use of air versus nitrous oxide (N2O) on postoperative oxygen (O2) saturation in blood was evaluated in 40 ASA Class I and II patients undergoing elective, open cholecystectomy. Patients were allocated randomly to two groups on the basis of whether they received air (Group A, n = 20) or N2O (Group B, n = 20) intraoperatively. Oxygen saturation was recorded on arrival of the patients in the ward, 24 h, and 48 h postoperatively. Although mean O2 saturation did not differ significantly (P > 0.05) between the groups over the first 24 h postoperatively, it was significantly higher (P < 0.05) in Group A as compared to Group B 48 h postoperatively. Incidence of hypoxemia (O2 saturation < 90%) was 40% in Group B as compared to 0% in Group A at the end of 48 h postoperatively. We conclude that the use of N2O during cholecystectomy is associated with a higher incidence of hypoxemia postoperatively. PMID- 8484514 TI - Does isoflurane alter mesenteric venous capacitance in the intact rabbit? AB - Volatile anesthetics act at a number of sites to alter cardiovascular function and the response of the cardiovascular system to barostatic reflexes. We examined the effects of isoflurane on reflex regulation of mesenteric venous capacitance vessels. To determine whether isoflurane alters mesenteric venous capacitance, continuous direct observations of mesenteric vein diameter, intravenous pressure, and mesenteric sympathetic efferent nerve activity (SENA) were made in 31 chloralose-anesthetized New Zealand white rabbits. Simultaneous measurements were obtained for aortic pressure and heart rate. The responses to changes in baroreceptor activation by means of either bilateral carotid occlusion (BCO) or aortic nerve stimulation (ANS) were studied in one group of 18 rabbits, while the response to direct electric activation by means of celiac ganglion stimulation (CGS) was studied in another group of 13 rabbits. In both groups, isoflurane vapor was administered at levels of 0.75% or 1.5%, and superfused isoflurane was administered directly to the vessel in doses of either 3% or 5% equilibrated with physiologic salt solution. Anesthetic levels were verified by mass spectrometry for expired gas and by gas chromatography for blood and superfusate levels. Inhaled isoflurane reduced hemodynamic variables and SENA in a dose-dependent fashion, but these same variables were unaffected by superfused isoflurane. One and one-half percent inhaled isoflurane abolished all reflex responses to baroreceptor stimulation in mesenteric capacitance veins and in SENA, but superfused isoflurane produced no corresponding attenuation of reflex responses to baroreceptor stimulation. Neither inhaled nor superfused isoflurane suppressed the reflex venoconstriction in response to CGS. Both inhaled and superfused isoflurane dilated the baseline vein diameter before stimulation. These results indicate that isoflurane dose increase the diameter of mesenteric venous capacitance vessels and inhibits reflex-induced constriction of mesenteric veins, whereas mesenteric sympathetic efferent nerve activity decreases and the reflex responses to activation of the carotid sinus and aortic baroreceptors are attenuated by inhaled isoflurane. The mechanism of this action appears to be primarily through the inhibition of central or peripheral sympathetic ganglionic transmission of barostatic control. PMID- 8484515 TI - Halothane inhibits the intraalveolar recruitment of neutrophils, lymphocytes, and macrophages in response to influenza virus infection in mice. AB - The effect of halothane anesthesia on the influenza A specific immune response and the pathogenesis of infection was evaluated in mice. Three-wk-old CD-1 mice were anesthetized with either 2% halothane for 2 h or ketamine (100 mg/kg intraperitoneally) and subsequently inoculated intranasally with a sublethal dose of influenza type A/PR/8/34 virus. Bronchoalveolar lavage was performed on animals from each group at 4 h postinoculation and daily thereafter for 14 days. Total and differential white blood cell counts were measured in the lavage fluid and the lungs were examined histologically for evidence of injury. Infected mice anesthetized with halothane had lower daily cell counts in the lung than animals anesthetized with ketamine and a marked change in cell type distribution. On Days 4 and 11 postinoculation, there were significantly (P < 0.05) more white blood cells in the lavage fluid of animals anesthetized with ketamine than halothane (mean/mL, 738,000 +/- SEM, 128,000 vs 196,000 +/- 51,400, respectively, and 1,020,000 +/- 227,000 vs 117,000 +/- 34,600, respectively). Differential counts were significantly higher (P < 0.05) in the ketamine group compared to the halothane for neutrophils on Day 4 (452,000 +/- 77,900 vs 72,000 +/- 46,000, respectively) and on Day 11 for lymphocytes (340,000 +/- 59,000 vs 33,000 +/- 17,000, respectively) and macrophages (480,000 +/- 120,000 vs 130,000 +/- 61,000). Infected mice that were given ketamine were qualitatively "sicker" than the halothane-treated group as evidenced by the appearance of ruffled fur, tachypnea, and cachexia. Animals anesthetized with ketamine demonstrated a greater degree of pulmonary histopathology including diffuse infiltration of macrophages, neutrophils, hemorrhage, and fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484516 TI - The use of needles in the practice of anesthesiology and the effect of a needleless intravenous administration system. AB - Anesthesia personnel are at risk for occupationally acquired blood-borne infections transmitted through needlestick injuries. To formulate strategies for the prevention of needlestick injuries, it is necessary to identify the types of needles used by anesthesia personnel and the devices associated with injuries. The introduction of a needleless intravenous (i.v.) administration system provided an opportunity to assess its effect on needle usage in the practice of anesthesiology. The contents of needle disposal containers placed in the preoperative holding area and five operating rooms before (control) and after the introduction of a needleless administration system (study) were categorized by needle type. The information on needles used by anesthesia personnel was compared with that on needles purchased for the entire hospital. During the control period, most of the needles used were 18-23-gauge hollow needles (51.6%), i.c. catheter stylets (23%), and 25-26-gauge small-bore hollow needles (17.1%). There was no difference in the total number of needles collected after the introduction of the needleless administration system, but there was an increase in capped 18 23-gauge hollow needles. Anesthesia personnel used a relatively greater number of small-bore hollow needles (25-26 gauge), i.v. catheters, and spinal and epidural needles, but fewer hollow needles (18-23 gauge) than were purchased for hospital wide use. Small-bore hollow needles (25-26 gauge) were responsible for 31.6% of the 19 needlestick injuries reported by anesthesia personnel to the Employee Health Service.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484517 TI - Probable venous air embolism during caudal anesthesia in a child. PMID- 8484518 TI - Probable venous air embolism during epidural placement in an infant. PMID- 8484519 TI - Is uvular edema a complication of endotracheal intubation? PMID- 8484520 TI - Complete airway obstruction caused by a pseudomembranous cast with subsequent negative pressure pulmonary edema. PMID- 8484521 TI - Anesthetic management of a patient with severe cold agglutinin hemolytic anemia utilizing forced air warming. PMID- 8484522 TI - Acute deterioration of mental status following epidural blood patch. PMID- 8484523 TI - Intravascular migration of an epidural catheter during postoperative patient controlled epidural analgesia. PMID- 8484524 TI - Severe hypotension during epidural anesthesia in a prazosin-treated patient. PMID- 8484525 TI - Cholestasis after interpleural bupivacaine for chronic upper limb pain. PMID- 8484526 TI - Forearm compartment syndrome following intravenous infusion with a manual "bulb" pump. PMID- 8484527 TI - Pediatric anesthesia without vascular access: intramuscular administration of atracurium. PMID- 8484528 TI - Is fentanyl appropriate for postoperative epidural PCA? PMID- 8484529 TI - The Augustine Guide as a fiberoptic bronchoscope guide. PMID- 8484530 TI - Concerning the complications of the Patil-Syracuse Mask. PMID- 8484531 TI - Delivery of excessive airway pressure to a patient by the anesthesia machine. PMID- 8484532 TI - Yet another place for the pulse oximeter probe. PMID- 8484533 TI - A modified portable system for oxygen supply using anesthetic rebreathing bags. PMID- 8484534 TI - Reducing epistaxis after nasogastric intubation. PMID- 8484535 TI - Broken inner sleeve of a Y-connector: course of a circuit leak and a potential foreign body aspiration. PMID- 8484536 TI - Another case report of opisthotonos and propofol. PMID- 8484537 TI - Inexpensive, convenient transducer holder. PMID- 8484538 TI - The cost of desflurane and propofol anesthesia. PMID- 8484540 TI - An alternative approach to intravenous regional anesthesia (IVRA) PMID- 8484539 TI - Bronchial or pulmonary artery obstruction by a transesophageal echocardiography probe? PMID- 8484541 TI - Epidural test dose and intravascular injection in obstetrics: sensitivity, specificity. PMID- 8484542 TI - Modification of a nasopharyngeal airway and transfusion extension tubing as an earpiece. PMID- 8484543 TI - DIC after intraoperative autotransfusion. PMID- 8484544 TI - Precipitous decrease in oxygen saturation during laparoscopic surgery. PMID- 8484545 TI - Venous air embolism during identification of the epidural space in children. PMID- 8484546 TI - The practice of anesthesiology and the package insert: decision-making regarding drug use in anesthesiology. PMID- 8484547 TI - Vaso-vagal reactions in an ambulatory surgery center. AB - This prospective study was undertaken to determine the incidence and factors predisposing to vaso-vagal reactions during venous cannulation in an ambulatory surgery population. In 141 ambulatory surgery patients, signs and symptoms of a reaction together with mean arterial pressure and heart rate were recorded at 1 min intervals during and for 6 min after venous cannulation. Overall, 10.6% of patients were symptomatic (95% confidence interval [CI] 6%-17%). The incidence was 16.6% (95% CI 8.4%-24.9%) in patients < or = 40 yr and 33.3% (95% CI 6.7% 60.0%) with a prior fainting history. Young age, duration or number of attempts at venous cannulation, and fainting history were independently associated with increased risk of a reaction (P < 0.03-0.004 by multiple repression analysis). Minimum mean arterial pressure was less in symptomatic patients than in those who were asymptomatic (58 mm Hg +/- 11.3 SD versus 82 mm Hg +/- 14.3 SD, P < 0.0001). We conclude that reactions occur commonly, particularly in the young or in patients with a history of fainting. Reactions are typically associated with significant hypotension that may require treatment. PMID- 8484548 TI - Desflurane versus propofol anesthesia: a comparative analysis in outpatients. AB - This study compares the induction, hemodynamic, and recovery characteristics of a general anesthetic with desflurane to one with propofol. Sixty outpatients presenting for orthopedic surgery received either a propofol induction of anesthesia followed by desflurane and nitrous oxide (Group 1), a propofol induction followed by propofol infusion and nitrous oxide (Group 2), a desflurane and nitrous oxide induction and maintenance (Group 3), or a desflurane induction and maintenance (Group 4). The quality of induction was inferior in Groups 3 and 4 with more breath-holding and excitation than in Groups 1 and 2. However, there was a more rapid emergence in Group 4 patients than any of the other groups. Group 4 patients were able to say their names (5.6 +/- 2.0 min vs 10.3 +/- 3.3 min, 8.6 +/- 3.1 min, and 9.3 +/- 1.5 min for Groups 1, 2, and 3, respectively) sooner after the discontinuation of anesthesia. Nonetheless, intermediate recovery was similar in Groups 2 and 4 being numerically but not statistically more rapid than in Groups 1 and 3. This pattern of intermediate recovery was also demonstrated by psychomotor function test results. Although there was no difference between the groups in postoperative narcotic requirement, more patients in Group 3 vomited (50%) than in either Group 2 (0%) or Group 4 (12.5%). Hemodynamically, the anesthetics were very similar. Although desflurane was a difficult drug to use for induction of anesthesia, this study demonstrates that desflurane is a suitable maintenance anesthetic for ambulatory surgery because it provides a rapid awakening and an intermediate recovery similar to propofol. PMID- 8484549 TI - Intraoperative hemodynamic changes are not good indicators of myocardial ischemia. AB - Intraoperative myocardial ischemia is associated with an increased risk of a perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. If reversible physiologic variables could be identified that are indicators of myocardial ischemia, treatment might be instituted early to prevent cardiac morbidity. In patients undergoing elective coronary artery bypass graft surgery, we evaluated the relationship between several premorbid patient characteristics, selected hemodynamic variables, intraoperative myocardial ischemia, and a PMI. In addition we evaluated these selected hemodynamic variables as intraoperative indicators of myocardial ischemia. The following variables were evaluated: heart rate, > 80 beats/min; systolic arterial blood pressure, > 160 mm Hg; systolic arterial blood pressure, < 80 mm Hg; mean arterial blood pressure, < 60 mm Hg; pulmonary artery diastolic pressure, > 18 mm Hg; a 5 mm Hg increase in pulmonary artery diastolic pressure; rate pressure product, > 12,000 beats/min.mm Hg; and a pressure rate quotient, < 1.0 mm Hg/beats/min. The premorbid patient characteristics selected were previous myocardial infarction, recent myocardial infarction (within 1 wk of surgery), type and number of coronary lesions, beta-blocker therapy, and calcium blocker therapy. One hundred consecutive (n = 100) patients for elective coronary artery bypass graft surgery were studied prospectively before the initiation of cardiopulmonary bypass (CPB). Patients were monitored with a Hewlett Packard computer ST segment analyzer using leads II and V5. Ischemia was defined as the new onset of ST segment deviation of > or = 1 mm from the baseline electrocardiogram (ECG) (preinduction) for at least 2 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484550 TI - Supplemental oxygen does not reduce myocardial ischemia in premedicated patients with critical coronary artery disease. AB - This randomized, prospective clinical study investigated the effects of supplemental inspired oxygen on arterial hemoglobin desaturation and myocardial ischemia in premedicated patients who have critical coronary artery stenosis, identified predictors for these adverse events, and examined the temporal relationship between hemoglobin desaturation and myocardial ischemia. Before elective coronary artery bypass surgery, 104 patients were monitored continuously by using a real-time electrocardiogram (V4 and V5 leads) recorder and a digital pulse oximeter. After a 2-h baseline monitoring period (Interval A), patients were given sublingual lorazepam 0.03 mg/kg, and were randomized to receive continuous supplemental inspired oxygen by nasal catheters [4 L/min (Oxygen Group, n = 52)] or to receive no supplemental inspired oxygen (Control Group, n = 52) (Interval B). One hour later, all patients received intramuscular morphine 0.15 mg/kg with perphenazine 0.05 mg/kg (Interval C). Interval C lasted 1 h, and the study was terminated. In the Oxygen Group, the incidence of desaturation was 25% before premedication and 11.5% after premedication (NS). In the Control Group after premedication, the incidence of desaturation increased from 25% to 56.9% (P < 0.001). There was no significant difference in the incidence of myocardial ischemia before or after premedication within or between the two groups. Arterial hemoglobin desaturation was not associated temporally with myocardial ischemia at any time. Predictors of desaturation after premedication included absence of supplemental O2, increased weight, age, and occurrence of desaturation before premedication. There were no identifiable predictors for myocardial ischemia after premedication. During Intervals A and C, episodes of hemoglobin desaturation were associated with small but statistically significant increases in mean heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484551 TI - Fentanyl plasma concentrations maintained by a simple infusion scheme in patients undergoing cardiac surgery. AB - The ability of a simple infusion scheme for fentanyl to achieve and maintain one of two target concentrations of fentanyl in plasma was studied in 17 patients having cardiac surgery that required the use of moderate hypothermic cardiopulmonary bypass (CPB). All patients received preanesthetic medication including morphine, a benzodiazepine, and/or scopolamine. Anesthesia was induced and maintained by one of two fentanyl infusion regimens: HIGH-FEN (n = 6), a priming infusion of 2.4 micrograms.kg-1 x min-1 for 20 min in combination with a continuous infusion of 0.3 microgram.kg-1.min-1 for the duration of the operation to produce a plasma fentanyl concentration of 20-25 ng/mL; or LOW-FEN (n = 11), priming and maintenance infusions of 2.4 and 0.15 micrograms.kg-1 x min-1 designed to produce a fentanyl concentration of 12-15 ng/mL of plasma. The six patients receiving HIGH-FEN had plasma fentanyl concentrations maintained between 20 and 27 ng/mL and none required anesthetic supplementation before CPB; one patient required a single dose of thiopental 50 mg after the termination of CPB. The total fentanyl dose for the operation (3.2 +/- 0.1 h) averaged 107 +/- 2 micrograms/kg (range 100.5-115.5 micrograms/kg). The 11 patients receiving LOW FEN had a plasma fentanyl concentration maintained below 20 ng/mL (range 13-17 ng/mL). Eight patients before and 10 patients after CPB required anesthetic supplementation for adverse hemodynamic or somatic responses. For comparison purposes, another eight patients received a single 75 micrograms/kg dose of fentanyl during 20 min for induction of anesthesia, and 7 of the 8 required supplemental anesthetic agents before and after CPB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484552 TI - Assessment of renal blood flow with contrast ultrasonography. AB - Sonicated albumin microspheres, a digitalizing ultrasound system, and a mathematical model for flow were used to determine whether blood flow in the canine kidney could be assessed with contrast ultrasound. Albunex ultrasound contrast microspheres were injected into the aorta while ultrasound images of the kidney and aorta were recorded simultaneously. Ultrasound data were obtained during contrast injections at 93 different renal blood flow rates in nine dogs. Contrast dose was calibrated to ultrasound system response for both aortic and renal images. A linear relationship between microbubble concentration used and pixel intensity was established (r = 0.89 for aortic images and r = 0.91 for renal images). Renal blood flow was manipulated from baseline by means of a hydraulic renal artery occluder and by intravenous dopamine or fenoldopam infusion. Blood flow calculated with contrast ultrasonography was compared with direct measurement obtained with an electromagnetic flow probe at each flow rate. Direct measurement correlated with rates calculated with contrast ultrasonography (r = 0.84, 95% confidence limits from 0.75 to 0.90). Overall, calculations tended to overestimate absolute flow measurements, and overestimation of flow tended to be greater during pharmacologically manipulated flow rates. We conclude the changes and trends in renal blood flow can be serially assessed in vivo with contrast ultrasonography, but technical limitations of present commercial ultrasounds systems preclude absolute quantification at this time. PMID- 8484553 TI - The effects of propofol on cerebral and spinal cord blood flow in rats. AB - The effects of low and high doses of propofol on global cerebral blood flow (CBF) and spinal cord blood flow (SCBF) as a function of mean arterial blood pressure were investigated. CBF and SCBF during propofol infusion were compared to the levels in rats anesthetized with nitrous oxide (N2O) and fentanyl. Rats in the fentanyl/N2O group (control, n = 13) received 70% N2O in O2 plus fentanyl (bolus: 10 micrograms/kg; infusion: 25 micrograms.kg-1 x h-1). Rats in the low-dose propofol group (n = 10) received 30% O2 in air and propofol infusion (0.5 mg.kg-1 x min-1). Rats in the high-dose propofol group (n = 8) received 30% O2 in air and propofol infusion (2.0 mg.kg-1 x min-1). Blood flow autoregulation was tested by manipulating the mean arterial blood pressure with phenylephrine infusion or trimethaphan infusion and blood withdrawal by measuring CBF and SCBF using radioactive microspheres. Arterial blood gases, pHa, and skull temperature were controlled. Cerebral and spinal cord vasculature showed autoregulation in all treatment groups with a pressure range of 50-140 mm Hg. Within this pressure range, when compared to fentanyl/N2O, propofol decreased cortical CBF 60% (P < 0.001), subcortical CBF 40% (P < 0.001), midbrain blood flow 30% (P < 0.001), and SCBF 20% (P < 0.05). These results indicate that propofol maintains CBF and SCBF autoregulation. PMID- 8484554 TI - Sedative doses of propofol increase beta activity of the processed electroencephalogram. AB - The effects of sedative infusions of propofol on the processed electroencephalograms (EEG) of eight healthy male volunteers were studied. EEG data for aperiodic analysis were collected during three 5-min periods: before propofol, during propofol infusion, and 30 min after termination of the infusion. After an initial dose of 1 mg/kg, subjects received a propofol infusion titrated to produce a standard level of conscious sedation. The infusion rate was 84 +/- 27 micrograms.kg-1 x min-1 (mean +/- SE) and plasma propofol levels were 2180 +/- 43 ng/mL. Total EEG power, defined as the sum of the squares of peak-to-peak amplitudes during each 5-s epoch, increased from 1350 +/- 295 microV2 x epoch-1 to 9675 +/- 2390 microV2 x epoch-1 during the propofol infusion (P < 0.05); it returned to 1445 +/- 145 microV2 x epoch-1 30 min after the infusion was discontinued (P < 0.05 vs the result during propofol). The change in total power was accompanied by a change in the distribution of power within the EEG spectrum, as the fraction of activity in the beta-band (12-35 Hz) increased during the infusion from 23% +/- 3% to 44% +/- 5% (P < 0.05). Thirty minutes after the infusion was terminated, the distribution of activity within the EEG spectrum had reverted to pre-propofol patterns. The similarity of EEG effects seen with sedative doses of propofol and benzodiazepines suggests that these drugs may share some neurochemical effects. PMID- 8484555 TI - Effect of atracurium-induced neuromuscular block on cortical motor-evoked potentials. AB - The effect of nondepolarizing neuromuscular block (NMB) with atracurium on transcranial magnetic motor-evoked potentials (tcMMEP) was examined in 10 adult cynomolgus monkeys. The monkeys were anesthetized initially with ketamine (15 mg/kg intramuscularly) and maintained with a continuous ketamine infusion (10-15 mg.kg-1 x h-1). NMB was then adjusted from no block to profound block and then back to no detectable block by adjustment of an atracurium infusion (0-7.25 mg.kg 1 x min-1). NMB was assessed by measuring the peak-to-peak amplitude of the evoked electromyographic (EMG) activity of the thenar muscles and by measuring the ratio of the 4th to 1st peak in the train of four (TOF) of the mechanical action from direct stimulation of the median nerve (direct EMG). NMB was adjusted incrementally, whereas cortical magnetic motor-evoked potentials were assessed by measuring the onset latency and amplitude of the thenar EMG response. Cortical stimulation was accomplished with a Cadwell MES-10 magnetic stimulator. tcMMEP and direct EMG amplitude and the mechanical response were reduced with increasing NMB. The average tcMMEP amplitude remained near baseline values (no NMB) until the direct EMG decreased < 0.4 of the unblocked value and when the TOF ratio decreased < 0.3. Further increases in NMB resulted in decreasing amplitude with a statistically significant reduction below baseline when the direct EMG decreased < 0.2 of baseline and TOF ratio decreased < 0.1. The tcMMEP onset latency was unchanged from baseline with TOF or with direct EMG reductions above 0.1 of baseline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484556 TI - The effect of fentanyl, sufentanil, and alfentanil on cerebral arterioles in piglets. AB - The effect of fentanyl, sufentanil, and alfentanil on cerebral arterioles was determined in 17 halothane-anesthetized newborn piglets. A closed cranial window was inserted over the parietal cortex, and changes in the luminal diameter of pial arterioles were measured by intravital microscopy as increasing concentrations of opioid (10(-9)-10(-5) M) were suffused over the cortical surface. Each opioid caused a dose-dependent decrease in arteriolar diameter that was attenuated by coadministration of naloxone (10(-5) M). Fentanyl was more potent than either alfentanil or sufentanil. Naloxone alone had no effect at concentrations < or = 10(-5) M, suggesting that endogenous opioids contribute little to resting cerebrovascular tone. These results indicate that fentanyl, sufentanil, and alfentanil produce cerebral vasoconstriction by action at an opioid receptor and that their vasoconstrictive potency appears to differ from their analgesic potency. PMID- 8484557 TI - A comparison of the cerebral protective effects of etomidate, thiopental, and isoflurane in a model of forebrain ischemia in the rat. AB - We evaluated the effect of etomidate, thiopental, and isoflurane on ischemic neuronal injury in rats. Control group animals received 1.2% isoflurane. The animals in the etomidate and thiopental groups received an infusion of either etomidate or thiopental until electroencephalographic (EEG) burst-suppression was attained. In the fourth group, the isoflurane concentration was increased to 3% (sufficient to produce EEG burst-suppression). Forebrain ischemia was induced by bilateral carotid artery occlusion with simultaneous hypotension for 10 min. Three days after ischemia, two blinded observers evaluated neuronal injury in coronal brain sections stained with hematoxylin and eosin. Injury to the ventral CA1 of the hippocampus was less in the etomidate group than in the control group. Injury to the entorhinal cortex was less in the thiopental group than in the control group. Histopathologic outcome in animals anesthetized with 1.2% isoflurane and 3% isoflurane was not different. Although these data indicate that etomidate and thiopental might reduce ischemic injury in some structures, the magnitude of the protective effects observed was small. PMID- 8484558 TI - Accelerated onset and delayed recovery of neuromuscular block induced by mivacurium preceded by pancuronium in children. AB - The goal of this study was to describe a technique which could shorten the time from mivacurium administration to peak neuromuscular block (NMB) after administration of the maximum recommended dose of mivacurium. Forty-eight pediatric patients were randomized into three groups and studied during nitrous oxide-alfentanil-thiopental anesthesia. Every patient received two blinded injections 3 min apart: either 15 micrograms/kg of pancuronium in 1 mL of saline followed by 170 or 200 micrograms/kg of mivacurium or saline followed by 200 micrograms/kg of mivacurium. Intravenous induction of anesthesia followed the first injection. Thenar electromyogram response to supramaximum train-of-four stimulation of the ulnar nerve at 10-s intervals was used for neuromuscular monitoring. Pretreatment with pancuronium significantly shortened the time to NMB and prolonged spontaneous recovery from NMB in comparison to the temporal course of NMB after administration of 200 micrograms/kg of mivacurium. Time from injection to 90% NMB averaged 116 (SEM 11) s after administration of 200 micrograms/kg of mivacurium, and 71 (7) s and 94 (11) s when 200 micrograms/kg or 170 micrograms/kg of mivacurium, respectively, was preceded by pancuronium (P = 0.0095). Mean times from injection to recovery of neuromuscular function to > 25% of baseline (T25) and to train-of-four ratio of 0.75 were 9.1 (0.7) and 15.8 (1.2) min, respectively, after administration of 200 micrograms/kg of mivacurium alone. T25 and train-of-four of 0.75 occurred significantly later at 21.9 (1.8) and 35.0 (2.8) min, respectively (P = 0.0001), when 200 micrograms/kg of mivacurium was preceded by 15 micrograms/kg of pancuronium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484559 TI - Computer simulation of geometry and hemodynamics of canine pulmonary arteries. AB - Assuming that along the pulmonary arteries, mathematical expectations of branching are equal to matrix (Ei,j; i: parent branch class, j: daughter branch class number), we made computer drafts of patterns of pulmonary arterial branching trees from the published data of canine pulmonary arterial casts with the "Monte Carlo methods" by FORTRAN, calculating from these data, the numbers of branches, size and resistance of the trees. We also analyzed blood flow distribution in a pulmonary branch according to the pathlength from the entrance of the tree. The graphics of the trees were similar to the original arterial casts, and numbers of the branches were nearly the same as the previous reported values. Calculated resistance was reasonable. The rate of blood flow per unit vessel in the short pathlength group was calculated as 1.5 times that of the long pathlength group of the same diameter. We believe that our method of describing the branching pattern matrix (Ei,j) provides a reasonable simulation of complex branching patterns such as pulmonary arteries and a useful means to analyze local hemodynamics. PMID- 8484560 TI - Tauberian-prony feature extraction technique for esophageal motility patterns. AB - For the esophageal contractile activity recorded during swallowing, a feature extraction scheme has been developed. It recognizes the time, duration, and amplitudes of local peaks for each peristaltic wave. The method is based on the Tauberian approximation for modeling waveforms as a sum of identically shaped pulses with different time delays and amplitudes. Initial conditions on the pulse properties are set and an optimal solution is sought. The method is completely automated and can be utilized for characterization and classification purposes. PMID- 8484561 TI - Modeling of the heart's ventricular conduction system using fractal geometry: spectral analysis of the QRS complex. AB - Many biological systems having one or more characteristics that remain constant over a wide range of scales may be considered self-similar or fractal. Geometrical and functional overview of the ventricular conduction system of the heart reveals that it shares structures common to a tree with repeatedly bifurcating "branches," decreasing in length with each generation. This system may further simplify by assuming that the bifurcating and decreasing process is the same at any generation, that is, the shortening factor and the angle of bifurcation are the same for each generation. Under these assumptions, the conduction system can be described as a fractal tree. A model of the heart's ventricles which consists of muscle cells and a fractal conduction system is described. The model is activated and the dipole potential generated by adjacent activated and resting cells is calculated to obtain a QRS complex. Analysis of the frequency spectrum of the QRS complex reveals that the simulated waveforms show an enhancement in the high frequency components as generations are added to the conduction system. It was also found that the QRS complex shows a form of an inverse power law, which was predicted by the fractal depolarization hypothesis, with a highly correlated straight line for a log-power versus log frequency plot with a slope of approximately -4. Similar results were obtained using real QRS data from healthy subjects. PMID- 8484562 TI - Complex bioelectric impedance measurement system for the frequency range from 5 Hz to 1 MHz. AB - Analytic techniques that have been successfully employed in materials science, and to a lesser extent in the study of biologic systems, have potential for improving the application of bioelectric impedance provided that both real and imaginary impedance components can be measured with sufficient accuracy over a given frequency range. Since biologic tissue, particularly animal tissue, is typically highly conductive, phase angles are small, making accurate measurements difficult. A practical four-terminal system employing commercial lock-in amplifiers is described and error sources and corrective techniques are discussed. PMID- 8484563 TI - Evaluation of regional load in acute ischemia by three-dimensional curvatures analysis of the left ventricle. AB - Geometric remodeling of the left ventricule (LV) following myocardial infarction and ischemic insult is associated with myocardial load redistribution. Regional curvatures based on 3-D reconstructions of the LV are used to calculate the regional loads. The technique uses surface normals to derive local circumferential and meridional curvatures. Following the validation of the procedure on simple geometric shapes, the effect of acute ischemia on the regional load redistribution was studied in six open chest dogs. Short axis magnetic resonance imaging (MRI) scans were used to reconstruct end-diastolic (ED) and end-systolic (ES) LV images by applying our helical shape descriptor, before and after acute coronary occlusion. Regional curvatures as well as local wall thickness by the volume element method were calculated before and after acute ischemia, and were used to approximate regional loads, by a regional stress index (sigma/P). Postmortem evaluation using monastral blue staining was used to divide each LV to normal (NZ), ischemic (IZ), and border (BZ) zones in the ischemic case, and to the anatomically matched regions in the preischemic LVs. Ischemia affects the local curvatures and loads both at ED and ES. At ED, sigma/P rose significantly only in the IZ. Similarly, at ES, the highest increase in load was detected in the IZ, but increases in circumferential and meridional load were seen in all regions. Identifying the load redistribution following acute ischemia helps delineate the mechanisms affecting geometric LV remodeling following myocardial infarction. PMID- 8484564 TI - Improved LAboratory Prototype ELectrolarynx (LAPEL): using inverse filtering of the frequency response function of the human throat. AB - The electrolarynx (EL) provides a valued means of verbal communication for people who have lost their larynx. Existing ELs have some drawbacks such as harsh, raucous, and unpleasant sound and the presence of background noise. This study presents an experimental analysis of two commercial ELs and describes the development and testing of an improved LAboratory Prototype ELectrolarynx (LAPEL) which more accurately simulates the sound of a natural larynx and has lower background noise. This natural sound is obtained by determining the frequency response function (FRF) of the tissue of the human neck and using this information to tailor the input signal to the EL by inverse filtering such that its output spectrum resembles that of the natural larynx. The result was subjectively judged to have a superior and more natural sound than existing electrolarynxes. PMID- 8484565 TI - Noninvasive characterization of the sound pattern caused by coronary artery stenosis using FTF/FAEST zero tracking filters: normal/abnormal study. AB - In this article, a new approach has been proposed to investigate the extraction of useful information from diastolic heart sounds caused by partially occluded coronary arteries. This method, which estimates and tracks the zeros (poles) of the diastolic heart sounds directly, takes advantage of the FTF/FAEST (Fast Transversal Filters/Fast a Posteriori Error Sequential) technique which possesses the fast convergence property of the Recursive Least Square (RLS) method and the computational simplicity of the Least Mean Square (LMS) method. In previous studies, the main assumption was that the diastolic heart sounds were a stationary process. Since the production of the heart sounds were a stationary process. Since the production of the heart sounds is not a stationary process, a new approach that performs well not only for stationary but also for nonstationary processes can be required. This requirement can be satisfied by the adaptive FTF/FAEST zero tracking method which provides fast and stable convergence as well as computational efficiency since the adaptive FTF/FAEST zero tracking method is based on the exact minimization of least squares criteria and the filter weights of this method are optimal at each time instant. The zero trajectories of the diastolic heart sounds were used to diagnose patients as diseased or normal. Results showed that the normal and abnormal records were incorrectly distinguished in only 6 of 35 cases using a blind protocol where analysis was done without knowledge of the actual disease states of the patients. The most discriminant time region of the zero trajectories of the diastolic heart sounds associated with coronary artery disease was between 200 and 300 msec after the second heart sound during the diastolic period. PMID- 8484566 TI - Signal analysis of noninvasive Xenon-133 cerebral blood flow measurements. AB - An anatomical model in conjunction with experimentally determined absorption data provides a framework to simulate signals as obtained from the noninvasive Xenon 133 cerebral blood flow technique. The contribution of individual tissue compartments to the total signal as well as the effect on the computed results were investigated under normal conditions. The introduction of physiological abnormalities into the model allowed the determination of sensitivity of the technique with respect to size, position, and perfusion level of the lesion. In addition, effects of cross-talk between hemispheres and signal overlap of adjacent detectors were quantified. It was found that the change of externally measured blood flow is proportional to the decrement/increment of flow in the lesion. Contrary to earlier reports, the effects of cross-talk and signal overlap were not found to be serious limitations in identifying lesions. PMID- 8484567 TI - Incorporating vessel taper and compliance properties in Navier-Stokes based blood flow models. AB - A popular and useful technique used to model blood flow in cardiovascular simulations is to divide each blood vessel into a series of segments, each with its own lumped resistance, inertance, and compliance parameters. The values of these parameters are usually obtained through a simplification of the Navier Stokes equations for fluid flow. However, the simplification often ignores the nonlinear and convective terms of the equations, resulting in errors in the parameter values, especially in the value found for resistance per unit length. We report a new method for the calculation of vessel resistance per unit length which takes into account the effects of vessel taper and wall compliance. It is shown that these effects can be addressed by the addition of two time-varying terms to the calculation of resistance per unit length. One term, due to vessel taper, is proportional to volumetric flow rate Q. The other term, due to vessel compliance, is proportional to delta p/delta t. These variables are readily available in computer simulations of blood flow in lumped parameter systems. Using data for the descending aorta, the new parameter values, when averaged over a cardiac cycle, compare favorably with results in the literature. PMID- 8484568 TI - Accuracy of a reflectance pulse oximeter in anesthetized horses. AB - The accuracy of a reflectance pulse oximeter was determined in 22 anesthetized horses. Oximetric blood oxygen saturation was measured with the pulse oximeter probe attached to the mucosa of the mandible. Arterial blood oxygen saturation (SaO2) was calculated from arterial blood gas values and the equine blood oxygen dissociation curve. The mean +/- SD difference between oximetric blood oxygen saturation and SaO2 was -1.3 +/- 3.1% for values of SaO2 ranging from 80 to 100%. The difference between oximetric blood oxygen saturation and SaO2 was influenced by SaO2, the mean arterial blood pressure, and preanesthetic medication administered, but not by age, sex, or body weight of the horse, individual animal effect, anesthetic induction or maintenance agent, procedure performed, body position, mode of lung ventilation, time of sampling, arterial pH, or carbon dioxide tension. PMID- 8484569 TI - Ultrasonographic observations of the flexor tendons and ligaments of the metacarpal region of horses. AB - Observations were made in dorsal and sagittal planes of the ultrasonographic mean gray scale of the flexor tendons and ligaments of the metacarpal regions of 5 Thoroughbred geldings, during weight bearing and nonweight bearing. In images made when the horses were nonweight bearing, the mean gray scale of the superficial and deep digital flexor tendons and accessory ligament was significantly reduced, but that of the interosseous medius muscle (suspensory ligament) was not. When relaxed, collagen fiber bundles in the tendons and ligaments acted as diffuse, rather than specular, reflectors of ultrasonic waves leading to localized regions of hypoechogenicity and a consequent reduction in mean gray scale. The suspensory ligament, however, remained under tension during nonweight bearing and so mean gray scale was not reduced. Analyses of the ultrasonographic mean gray scale have the potential to provide quantitative data relating to the changes in echogenicity that develop in injured equine tendons and ligaments. PMID- 8484570 TI - Distribution of dopamine beta-hydroxylase and neuropeptide Y-immunoreactive nerves in healthy equine lungs. AB - Immunohistochemical methods were used to determine the distribution of pulmonary nerves containing either an enzymatic marker of adrenergic nerves, dopamine beta hydroxylase, or the putative neurotransmitter neuropeptide Y in 7 equids with healthy lungs. Nerves immunoreactive for these substances were found on airway smooth muscle in nearly all the samples of healthy equine lung examined. These nerves were generally more numerous in the larger airways but could be detected even in noncartilaginous bronchioles. Pulmonary and bronchial vessels also contained numerous immunoreactive nerves. On the basis of these findings, we suggest that dopamine beta-hydroxylase- and neuropeptide Y-immunoreactive nerves may be involved in the regulation of airway and vascular diameter in equids. PMID- 8484571 TI - Expression of calbindin-D28k in developing and growing ovaries of chicken embryos. AB - Immunoreactivity for 28 kd vitamin D-dependent calcium-binding protein (calbindin D28k) has been localized in the germinal epithelium and cells surrounding oogonia and oocytes (future granulosa cells) of developing and growing ovaries of chicken embryos. The protein first appeared prominently in the germinal epithelium of the developing left ovary in 8-day embryos. At the twelfth day of incubation, cells surrounding oogonia and oocytes reacted intensely for calbindin-D28k. The number and intensity of calbindin-D28k-containing cells increased in both types of cells as the embryos further developed. Calbindin-D28k remained in the germinal epithelium throughout the study period observed (up to 10 weeks). However, the protein was present transiently in the future granulosa cells. It gradually decreased after hatching, and was virtually absent from granulosa cells in a 10 week old chicken. Compared with the known process of onset of sexual development, these results indicated possible involvement of calbindin-D28k in the early phases of oogenesis in chicken ovaries. PMID- 8484573 TI - In vitro susceptibility of Actinobacillus pleuropneumoniae strains to 42 antimicrobial agents. AB - Minimal inhibitory concentration of 42 antimicrobial agents was determined against 57 field strains of Actinobacillus pleuropneumoniae isolated from pigs in Spain. Penicillins, aminoglycosides, and tetracyclines had irregular activity; ticarcillin, tobramycin, and doxycycline were the most active of each group, respectively. Macrolides, vancomycin, dapsone, and tiamulin, to which strains had high rate of resistance, were almost ineffective. Thiamphenicol, colistin, rifampin, fosfomycin, mupirocin, and metronidazole had good activity, with resistance ranging between 0 and 8.8%. Finally, cephalosporins (except cephalexin) and quinolones (especially ciprofloxacin, enrofloxacin, and sparfloxacin) were the most active antibiotics against A pleuropneumoniae. PMID- 8484572 TI - Clinical and laboratory changes after administration of milbemycin oxime in heartworm-free and heartworm-infected dogs. AB - Adverse reactions to oral administration of milbemycin oxime were investigated in heartworm (HW)-free and HW-infected dogs given either the minimal HW prophylactic dose (0.25 mg/kg of body weight) or the hookworm anthelmintic dose (0.5 mg/kg). In 12 HW-free control dogs treated with lactose excipient (100 mg/kg), abnormal signs were not observed. There were no differences between the 2 doses in prevalence of clinical signs of disease and laboratory test results. In 60 HW free dogs (50 dogs administered the low dose, and 10 dogs given the high dose) and 46 nonmicrofilaremic HW-infected dogs (35 dogs administered the low dose, and 11 dogs given the high dose), only a transient and slight paleness of the visible mucous membranes, intestinal hyperperistalsis, or both were observed in some dogs. In 77 microfilaremic (MF) dogs (41 dogs administered the low dose, and 36 dogs given the high dose), weakness or loss of appetite was observed in 13 dogs (16.9%). Paleness of the visible mucous membranes was observed in 16 dogs (20.8%), intestinal hyperperistalsis was observed in 27 dogs (35.1%), and respiratory signs, such as mild labored respiration, were observed in 13 dogs (16.9%). Dullness of heart sounds was noticed in 4 dogs (5.2%). In 12 (9 dogs administered the low dose, and 3 dogs given the high dose) of 89 MF dogs (13.5%), adult heartworms migrated from the pulmonary arteries to the right atrium, causing signs of caval syndrome, including heart murmurs, jugular pulsations, and weakness. In HW-free dogs, rectal temperature tended to decrease gradually, and heart and respiratory rates were transiently decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484574 TI - Effects of dietary electrolyte balance on subluxation of the femoral head in growing dogs. AB - Effects of increased dietary chloride and reduced sodium and potassium ion concentrations on coxofemoral joint conformation, as assessed by radiography, were examined in growing dogs. Dietary electrolyte balance was quantified by dietary anion gap (DAG), defined as Na+ + K+ - Cl- in milli-equivalents per 100 g of food. Diets had anion gap ranging from 8 to 41 mEq/100 g of food. One hundred sixty-seven pups from 27 litters representing 5 breeds were studied during the period of rapid growth. The extent of subluxation of the femoral head was measured on radiographs, using the method of Norberg. On average, less subluxation of the femoral head (P < 0.05) was observed when diets with lower DAG were fed. Differences in DAG balance did not result in different rates of weight gain; therefore, the reduction in coxofemoral joint subluxation attributable to low DAG was unrelated to weight gain. Norberg angles measured at 30 weeks of age were highly correlated with coxofemoral joint status at 2 years of age, as measured by the Swedish diagnostic system and the scoring system of the Orthopedic Foundation for Animals (lrl > or = 0.70, P < 0.0002, n = 24). This diet-related improvement in coxofemoral joint subluxation would be expected, on average, to delay or mitigate the characteristic clinical and radiographic signs of hip dysplasia in growing dogs. PMID- 8484575 TI - Comparison of taurine, alpha-tocopherol, retinol, selenium, and total triglycerides and cholesterol concentrations in cats with cardiac disease and in healthy cats. AB - Epidemiologic relations were evaluated between plasma concentrations of nutrients and cardiovascular diseases. A total of 220 cats were assessed: 144 cats with noninduced acquired heart disease and 76 clinically normal cats. Plasma was assayed for taurine, alpha-tocopherol, selenium, retinol, and total cholesterol and triglycerides concentrations. Cardiovascular disease groups included dilated cardiomyopathy (n = 53), left ventricular hypertrophy (n = 28), hyperthyroidism (n = 11), and uncertain classification (n = 52). In cats with dilated cardiomyopathy, mean plasma taurine concentration was the lowest of that in cats of any group, being only 38% of the value in healthy cats; females had less than half the mean value of males. Tocopherol concentration was 20% lower than normal, and retinol concentration was 40% higher than normal. Total cholesterol concentration was 36% lower than normal. Triglycerides concentration was higher in these cats than in any other group--twice the value recorded in healthy cats and 67% higher than that in hyperthyroid cats. In cats with hypertrophic cardiomyopathy, almost 15% had mean plasma taurine concentration < 30 mumol/L. Retinol concentration was 15% higher, and triglycerides concentration was 54% higher than normal. Approximately 27% of hyperthyroid cats had mildly decreased plasma taurine concentration. Hyperthyroid cats had the lowest tocopherol and cholesterol values; both were at least 30% lower than normal. Retinol concentration was 30% higher than normal. Approximately 14% of cats with uncertain classification had mildly decreased plasma taurine concentration. Plasma retinol and triglycerides concentrations were higher than normal in 25 and 38% of these cats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484576 TI - Correlations between histologic endometrial lesions in mares and clinical response to intrauterine exposure with Streptococcus zooepidemicus. AB - The relationship between histologic lesions in endometrial biopsy specimens and susceptibility to chronic uterine infection (CUI) in mares was investigated. Mares were allotted to 4 groups on the basis of degree of endometrial lesions. Mares in group 1 (n = 6) had no pathologic changes, mares in group 2 (n = 5) had only mild pathologic changes, group-3 mares (n = 7) had moderate changes, and group-4 mares (n = 7) had severe inflammatory and fibrotic endometrial changes. Susceptibility to CUI was determined by the inflammatory response to intrauterine inoculation of 5 x 10(6) Streptococcus zooepidemicus. The inoculum was given on the third day of behavioral estrus and in the presence of a follicle > 30 mm. Mares with > 1 neutrophil/5 high-magnification (400 x) microscopic fields and > 20 colonies of S zooepidemicus at 96 hours after inoculation were considered to be susceptible to CUI. There was a significant association between biopsy grade and susceptibility to CUI among the groups. Histologically normal endometrium was associated with resistance to CUI, and severe histopathologic changes in the endometrium were associated with susceptibility to CUI. Mild to moderate endometrial lesions did not correlate consistently with susceptibility or resistance to CUI. PMID- 8484577 TI - Pharmacokinetics and concentrations of ceftiofur sodium in body fluids and endometrium after repeated intramuscular injections in mares. AB - Each of 5 healthy mares was given 5 consecutive IM injections of ceftiofur sodium (2 mg/kg of body weight; 50 mg/ml) at 12-hour intervals. Ceftiofur concentrations were measured serially in serum, synovial fluid, peritoneal fluid, and urine, and were measured in CSF and endometrial tissue after the fifth dose. Mean elimination rate constant was 0.354 +/- 0.101 h-1 and elimination half-life was 2.49 +/- 0.49 hour. Mean serum ceftiofur concentrations peaked approximately 1 hour after each injection. The highest mean ceftiofur concentration was 5.09 micrograms/ml at 1 hour after the fifth dose for serum, 3.02 micrograms/ml at 2 hours after the fifth dose for synovial fluid, and 3.23 micrograms/ml at 4 hours after the fifth dose for peritoneal fluid. Mean urine concentrations reached 15.72 micrograms/ml at 1 hour after the fifth dose. Ceftiofur was not detected in CSF or endometrial tissue. None of the mares had adverse reactions to the drug. PMID- 8484578 TI - Pharmacokinetics of cefotaxime in neonatal pony foals. AB - Serum concentrations of cefotaxime and desacetylcefotaxime were measured in 1 week-old pony foals after IV administration of a single dose of cefotaxime. The cefotaxime disposition data conformed to a two-compartment model with elimination half-life of 0.60 hour. The combined cefotaxime and desacetylcefotaxime data was best described by a four-compartment model. The apparent half-life describing the disappearance of desacetylcefotaxime was 1.69 hours. Dosage of 40 mg/kg of body weight given IV every 4 to 6 hours for neonatal foals with gram-negative septicemia and every 2 hours for foals with meningitis is recommended for further study. PMID- 8484579 TI - Blockade of endotoxin-induced cecal hypoperfusion and ileus with an alpha 2 antagonist in horses. AB - Stimulation of alpha 2 adrenergic receptors inhibits colonic motility and may constrict some peripheral vascular beds. Endotoxemia elicits release of sympathetic neurotransmitters and increases sympathetic nerve activity, which may result in stimulation of alpha 2 adrenergic receptors. The objective of this study was to determine whether blockade of alpha 2 adrenergic receptors would restore cecal motility and blood flow during endotoxemia in horses. Strain-gauge force transducers and ultrasonic flow probes were used to measure cecal and colonic mechanical activity and lateral cecal arterial blood flow. Intravenous infusion of endotoxin (cumulative dose of 0.03 mg/kg) significantly decreased cecal and right ventral colon contractile activity and lateral cecal arterial blood flow. Slow IV infusion of yohimbine (cumulative dose of 75 micrograms/kg) significantly attenuated those effects of endotoxin. On the basis of our findings, we concluded that endotoxemia causes cecal and proximal colonic ileus and cecal hypoperfusion via a mechanism that involves alpha 2 adrenergic receptors. PMID- 8484580 TI - Characterization of serum alpha 1-acid glycoprotein in fetal and newborn calves during development. AB - Serum alpha 1-acid glycoprotein (alpha 1-AG) in bovine fetuses and newborn calves was characterized. Serum alpha 1-AG concentration increased during fetal development and neonatal stages. Mean +/- SD serum alpha 1-AG concentration reached a peak of 1,368 +/- 207 micrograms/ml immediately after birth, but thereafter gradually decreased to 249 +/- 100 micrograms/ml, similar to the normal adult bovine range. By use of isoelectric focusing of thin-layer gels, we detected 7 microheterogeneity bands ranging from pI 3.2 to 3.8 in adult bovine serum. Twelve bands ranging from pI 2.6 to 3.8 were found in 9-month fetuses and in neonates. The 5 most-acidic bands, which are absent in adult serum, ranged between pI 2.6 and 3.1 and decreased with maturation as band patterns assumed adult characteristics. By crossed affinity electrophoresis, alpha 1-AG of adult bovine serum was separated into 4 peaks according to its differential affinity to concanavalin A (conA). Seventy-five percent of the alpha 1-AG concentration was represented by peak 3 (P-3) and peak 4 (P-4), which had moderate or strong binding to conA. In contrast, fetal sera contained only peak 1 (P-1), which did not have conA-binding affinity. In neonatal sera, 4 peaks were recognized, of which P-1 comprised 70% of the total alpha 1-AG. Thereafter, with aging, percentage of P-3 and P-4 increased as band composition approached the normally expected adult pattern. PMID- 8484581 TI - Effects of acute physical stress on immune competence in pigs. AB - Some interrelations between physical stress and immune competence were studied in pigs. One group of pigs underwent 2 intense short-term treadmill exercise tests, separated by an interval of 1 week, and another group served as controls. In vitro production of interferon alpha by blood mononuclear cells and the ability of lymphocytes to proliferate and produce interleukin 2 were chosen as markers of immune competence; plasma concentrations of cortisol, lactate, and purines were used as markers of physical stress. Blood samples were drawn from a catheter in situ 60 minutes before, immediately after, and at 10, 30, and 60 minutes, and 7, 24, and 72 hours after exercise. Physical stress resulted in immediate increase in the plasma concentrations of cortisol, lactate, and hypoxanthine, but had no effect on the blastogenic capability of lymphocytes or on their interleukin-2 production on either of the test occasions. Ability of blood mononuclear cells to produce interferon alpha in vitro was not affected by exercise stress. PMID- 8484582 TI - Electrocardiographic findings in rats with cardiomyopathy. AB - The purpose of this study was to evaluate changes in the ECG in a strain of rats, SHHF/Mcc-cp that developed cardiomyopathy and congestive heart failure naturally. Lead-I, -aVF, and -V5 ECG were obtained from male rats at approximately 6, 10, and 19 months of age, corresponding to early, mild, and severe heart failure, respectively. Electrocardiograms also were obtained from male Wistar-Furth rats matched for age with SHHF/Mcc-cp rats. Heart rate, amplitude and duration of component deflections, degree of notching of P waves and QRS complexes, and orientation of means QRS vectors in the frontal plane were analyzed from the ECG. Durations of P waves, PQ intervals, QRS complexes, and QT intervals were prolonged and amplitude of R waves in lead aVF was decreased only in SHHF/Mcc-cp rats at the 19-month recording. Increased notching in QRS complexes, but not in P waves, was observed more frequently at all ages, in SHHF/Mcc-cp rats than in Wistar rats, and notching was greatest at 19 months. Arrhythmias were not observed in Wistar rats, but infrequent supraventricular premature depolarizations were observed in 2 of 10 SHHF/Mcc-cp rats at 19 months. In leads aVF and V5, T waves increased in amplitude as Wistar rats aged; however, in SHHF/Mcc-cp rats, T-wave amplitude peaked in all leads at 10 months, but returned to the 6-month value at month 19. We conclude that cardiomyopathy, heart failure, or both, resulted in changes in the ECG, but that these changes could be used to detect heart failure only when rats reached 19 months of age and were severely affected. PMID- 8484583 TI - Contributions to variance in force-plate analysis of gait in dogs. AB - Coefficients of variation were calculated for peak vertical force and for vertical, cranial, and caudal impulses recorded from the left forelimb and left hind limb of 5 dogs that were trotted across a force plate 5 times by 5 handlers. To determine the percentages of variance attributable to dogs, handlers, and trial repetitions, data recorded for each force measurement were analyzed according to a two-factor ANOVA. Coefficients of variation for peak vertical forces and for vertical impulses varied between 5.8 and 8.5%. Coefficients of variation for the forelimb cranial and caudal impulses and for the hind limb cranial and caudal impulses were 26.4 and 30.5%, and 63.0 and 25.9%, respectively. The percentage of the total variance attributable to dogs and to trial repetitions ranged from 14 to 69% and from 29 to 85%, respectively, depending on the force or impulse evaluated. The percentage of variance attributable to handlers varied between 0 and 7%. The trivial amount of variation attributable to handlers indicated that multiple handlers may be used in experiments without an appreciable influence on the results. PMID- 8484584 TI - Clinicopathologic findings after experimental implantation of synthetic intraocular lenses in dogs. AB - Clinical findings indicate that canine eyes tolerate implantation of polymethylmethacrylate (PMMA) intraocular lenses (IOL) well, although inflammation and ocular damage attributable to the implants is not known. The use of silicone or polyhydroxyethylmethacrylate (HEMA) IOL has not been reported in dogs. In this study, 15 conditioned, mixed-breed dogs were allotted to 3 groups: 5 received PMMA IOL; 5 received silicone IOL; and 5 received HEMA IOL. The IOL optic was inserted into the anterior chamber of the right eye and anchored to the cornea. An identical surgical procedure was done on the left eye, except that no lens optic was inserted. Clinical examination and measurement of corneal thickness were done immediately prior to and after surgery. Aqueous humor samples were collected at the time of surgery and 28 days after surgery. Only mild and transient inflammation was observed in IOL-implanted eyes. On several postoperative days, it was found that PMMA IOL induced significantly greater corneal thickness, aqueous flare, anterior uveal irritation, and corneal edema than did other IOL. Significantly more anterior uveal irritation and increased aqueous humor protein concentration was observed with HEMA IOL than with PMMA or silicone IOL. Silicone IOL induced significantly less fibrin deposition than did PMMA or HEMA IOL. PMID- 8484585 TI - Relation between reduced glutathione content and Heinz body formation in sheep erythrocytes. AB - To clarify the oxidant defense functions of reduced glutathione (GSH) in erythrocytes, the effect of GSH deficiency on in vitro oxidant defense was studied, using GSH-deficient sheep erythrocytes (low-GSH cells). The formation of Heinz bodies in low-GSH cells was higher than that in high-GSH cells when the cells were incubated with an oxidant drug, acetylphenylhydrazine (APH). Artificial depletion of GSH by 1-chloro-2,4-dinitrobenzene in high-GSH cells resulted in increased Heinz body formation in these cells incubated with APH. Furthermore, high negative correlation was observed between Heinz body formation and GSH content in sheep erythrocytes exposed to APH. These results clearly indicate that erythrocyte GSH is indispensable for erythrocyte defense against oxidative damage induced by APH, and support the previous observations that sheep with low-GSH erythrocytes were more susceptible to oxidative agents than were sheep with high-GSH erythrocytes. PMID- 8484586 TI - Kinematic gait analysis of the trot in healthy greyhounds. AB - A noninvasive computer-assisted kinematic gait analysis was used to describe flexion and extension movements of 6 joints in Greyhounds at a trot. Distinct patterns of movements were described for each joint studied. The coxofemoral and carpal joints were characterized by a single peak of maximal extension. The femorotibial, tarsal, scapulohumeral, and cubital joints had 2 peaks of maximal extension, with 1 peak preceding stance phase and a second peak within stance phase. A two-factor repeated-measures ANOVA was used to determine the variance in measurement of joint angles in degrees that was attributable to trial repetitions and to differences between dogs. The coxofemoral, femorotibial, tarsal, scapulohumeral, and cubital joints had a mean variance attributable to trial repetition of 6.6 (range, 1.7 to 12.9), and a mean variance attributable to differences between dogs of 5.1 (range, 0.9 to 9.2). The carpus had more variance, with a mean variance attributable to trial repetition of 16.3 (range, 13.3 to 20.5), and that attributable to differences between dogs of 31.8 (range, 20.5 to 46.7). Kinematic gait analysis provided a reliable description of flexion and extension movements in Greyhounds with minimal variance attributable to trial repetitions and to differences between dogs. PMID- 8484587 TI - Preparation and transfusion of canine platelet concentrates. AB - A protocol was developed for preparation of platelet concentrates (PC) to support thrombocytopenic dogs. Four clinically normal dogs with platelet counts that ranged from 200 to 330 x 10(9) platelets/L were used as donors. One unit (450 ml) of blood was collected by venipuncture into a double blood bag. Whole blood (WB) was centrifuged for 4 minutes at 1,000 x g (braking time = 2 minutes, 30 seconds) to prepare platelet-rich plasma (PRP). The PRP was expressed into the satellite bag and was centrifuged for 10 minutes at 2,000 x g (braking time = 2 minutes, 36 seconds). The platelet-poor plasma was expressed, leaving 40 to 70 ml of plasma and the pelleted platelets in the satellite bag. The resulting PC was left undisturbed for 60 minutes to promote disaggregation, and the platelets were then resuspended by gentle manual agitation. Forty-eight PC were prepared. Mean (+/- SD) platelet yield from WB to PRP was 78 (+/- 13)% (range, 35 to 97%); yield from PRP to PC was 94 (+/- 6)% (range, 75 to 100%); and overall yield (PC from WB) was 74 (+/- 13)% (range, 36 to 91%). Mean PC platelet count was 8.0 (+/- 3.0) x 10(10) platelets/PC (range, 2.3 to 13.4 x 10(10) platelets/PC). The WBC content was 0.1 to 2.3 x 10(9) platelets/PC, representing 3 to 74% of WBC in the WB. Hematocrit was 0.1 to 26.2%. Results of bacterial and fungal culturing were negative. The PC were irradiated (18 Gy) and transfused to 5 cross-matched dogs undergoing bone marrow transplantation that developed profound thrombocytopenia of up to 8 weeks' duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484588 TI - Hillary Clinton seeks nursing's input on reform. PMID- 8484589 TI - Liaison nurses ensure continuity of care. PMID- 8484590 TI - Implementing the Safe Medical Devices Act. PMID- 8484592 TI - Why give to ANA-PAC? PMID- 8484591 TI - Syringe attack by AIDS patient may be first documented. PMID- 8484593 TI - Nurses must be visible in political arena. PMID- 8484594 TI - Activism in '92: the political year in review. PMID- 8484595 TI - ANA: one year in Washington. PMID- 8484597 TI - Texas nurse takes her place in Congress. Interview by Robin A Cassetta. PMID- 8484596 TI - CDC/SC network: the force behind ANA's political action. PMID- 8484598 TI - Students embrace political activism. PMID- 8484599 TI - Preparing nursing for the 21st century. PMID- 8484600 TI - Second focus group discusses reform. PMID- 8484601 TI - Women's health concerns integral to reform. PMID- 8484602 TI - Grassroots lobbying: influencing the legislative process. PMID- 8484603 TI - ANA endorses cataract guideline. Interview by Joan B Meehan. PMID- 8484604 TI - Educate patients on critical need for donors. PMID- 8484605 TI - Correctional facilities experience TB outbreaks. PMID- 8484606 TI - Community nursing organization project shapes future of health care. PMID- 8484607 TI - Life insurance: preparing for your family's future. PMID- 8484609 TI - One nurse can make a difference. As I see it. PMID- 8484608 TI - Positions abound for advanced practice nurses. PMID- 8484610 TI - Nurses, the White House and health care reform. PMID- 8484611 TI - Elected officials provide a variety of perspectives on health care reform. PMID- 8484612 TI - No bandwagon, yet. Inhaled nitric oxide (NO) for neonatal pulmonary hypertension. PMID- 8484613 TI - Effect of inhaled nitric oxide during group B streptococcal sepsis in piglets. AB - Group B streptococcus (GBS), a common gram-positive pathogen, causes similar pathophysiologic changes in newborn humans and animals. Infusion of GBS into neonatal animals produces pulmonary hypertension and ventilation/perfusion (Va/Q) mismatch in both early-phase (< 1 h) and late-phase (2 to 6 h) responses. Contrary to early phase, late phase causes pulmonary vascular injury. Nitric oxide (NO) is an inhaled vasodilator whose effect on pulmonary hypertension and Va/Q matching during early and late phases of GBS sepsis is unclear. We hypothesized that inhaled NO (150 ppm) would: (1) reverse early-phase GBS-induced pulmonary hypertension; (2) demonstrate less effectiveness in reversing late phase GBS-induced pulmonary hypertension because of vascular injury; (3) improve late-phase GBS-induced Va/Q mismatching. Anesthetized, mechanically ventilated piglets (n = 10; 14 +/- 4 days of age) received a 240-min infusion of GBS (1.5 x 10(9) CFU/kg/h). Piglets received 30 min of NO (Study) or N2 (Control) at 30 and 210 min of GBS infusion. We found that inhaled NO selectively reversed early- and late-phase GBS-induced pulmonary hypertension and that NO was equally as effective in each phase. Inhaled NO did not reverse Va/Q mismatching during late phase GBS. We conclude that 4 h of GBS sepsis does not injure neonatal pulmonary vascular smooth muscle sufficiently to impair its response to inhaled NO. PMID- 8484614 TI - Exogenous surfactant rapidly increases PaO2 in mature rabbits with lungs that contain large amounts of saline. AB - Neonatal respiratory distress syndrome (RDS) is characterized by a relative surfactant deficiency and air-space edema. We tested the hypothesis that exogenous surfactant would improve gas exchange in mature surfactant-replete lungs containing large amounts of saline. Healthy young rabbits weighing 550 to 1,000 g were anesthetized and tracheotomized, and they received assisted ventilation with a FlO2 = 1. Baseline PaO2 decreased when 20 ml/kg of warmed saline (n = 6) was instilled into the lung; average PaO2 was stable and remained less than 200 mm Hg during the next 180 min. When either 50 mg/kg of natural surfactant (n = 6) or lipid-extracted surfactant (LES) (n = 6) was included in the saline solution, the PaO2 was higher (p < 0.05) than in the saline-alone group. To evaluate the effect of delayed addition of the surfactant we performed six additional experiments; the PaO2 fell to 60 +/- 6.9 SEM mm Hg after saline instillation, but within 15 min of administering LES, the PaO2 increased to 246 +/- 44.1 mm Hg, and it rose to 469 +/- 29.6 mm Hg by the end of the experiment (t = 180 min). Similar ventilator settings maintained comparable PaCO2 values in untreated and surfactant-treated groups. Gravimetric lung water contents (ml/kg body weight or ml/total lung hydroxyproline content) were markedly increased, but similar, in all groups. These studies show that the increase in PaO2 after surfactant administration to mature lungs containing large amounts of saline is similar to the increase in PaO2 seen when surfactant is given to premature infants with RDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484615 TI - Four markers of collagen metabolism as possible indicators of disease in the adult respiratory distress syndrome. AB - During the adult respiratory distress syndrome (ARDS), an irreversible fibrotic process can occur extremely rapidly. To establish indices of ARDS in pneumonia as well as the severity of the lung fibrosis, we have undertaken for the first time a study of four markers of collagen metabolism obtained from both bronchoalveolar lavage fluid (BALF) and serum: Type I (CI), Type III (CIII), N-terminal peptide of Type III procollagen (PIIINP), and galactosylhydroxylysylglucosyltransferase activity (GGT). We studied 61 patients (13 coma controls, 29 with pneumonia, and 19 with ARDS). In BALF, the average values of CI, CIII, PIIINP, and GGT were significantly higher in ARDS than in the control patients. The values for patients with pneumonia, although increased, were significantly lower than those in ARDS for CI, CIII, and PIIINP. In serum, the mean CI and PIIINP were significantly increased in pneumonia and ARDS, but the mean CIII was significantly increased only in ARDS compared with the control group. Significant positive linear correlations were observed for ARDS between CI and CIII or PIIINP and CIII in BALF and serum. Such correlations were observed for pneumonia only in serum. Molecular mass determinations demonstrated that CI- and CIII-related antigens in BALF were essentially intact triple helices of collagens or procollagens. Among patients with histologically defined interstitial fibrosis, the level of PIIINP in BALF was significantly higher for those with an additional intraalveolar fibrosis. In conclusion, measurements of these collagen markers may be useful for assessing disease activity and reflecting the flux of collagen molecules in the lung. PMID- 8484616 TI - Increased pulmonary response to inhaled endotoxin in lactating rats. AB - An important aspect of risk assessment is identification of subpopulations particularly susceptible to the effects of inhaled pollutants. The present study examined whether female rats were more sensitive during lactation to the acute pulmonary injury produced by inhaled endotoxin. Lactating and age-matched virgin female rats were exposed to aerosols of saline or endotoxin for 3 h and lavaged at 24 h after exposure. No significant differences in lactate dehydrogenase, beta glucuronidase, total protein, and total cell and PMN counts were observed between virgin and lactating rats after exposure to saline. Each marker of pulmonary injury except beta-glucuronidase was 1.5- to 3-fold greater in lactating than in virgin female rats exposed to 29.6 micrograms/m3 endotoxin. PMNs (6-fold), total cell counts, and protein were also significantly increased (p < 0.05) in lactating rats exposed to 1.3 micrograms/m3 endotoxin, a concentration reported to occur in a number of agricultural settings. These results demonstrate that the physiologic state of lactation is associated with an increased sensitivity to the acute pulmonary injury produced by inhaled endotoxin and are consistent with previous work demonstrating a similar increased sensitivity to ozone exposure. The possibility of a similar pattern of enhanced response in analogous groups of humans merits examination. PMID- 8484617 TI - Acute exposure to acid fog. Effects on mucociliary clearance. AB - Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484618 TI - Prevalence of exercise-induced airway narrowing in schoolchildren from a Mediterranean town. AB - A cross-sectional study was carried out on a random sample of 2,216 schoolchildren 9 to 14 yr of age to determine the prevalence of exercise-induced airway narrowing (EIAN) in a Mediterranean town (Mataro). A complementary case control study measured the association between EIAN and respiratory symptoms. A free-running test was performed during school time. Peak expiratory flow rate (PEFR) was measured at rest and at 2, 5, 10, and 15 min after exercise. A total of 136 of 2,056 satisfactory runs showed a decrease of PEFR equal to or higher than 15% at each of these times after exercise. Five more children developed wheezing during running and were considered to have EIAN. Prevalence of EIAN was 6.9% (95% CI = 5.9 to 7.9). Prevalence decreased progressively with age. No sex difference was found. In the case-control study a questionnaire of respiratory symptoms was applied to the mothers of hyperresponsive children, as well as to two matched control subjects for each case. Questionnaire analysis showed a strong association between EIAN and respiratory symptoms or rhinitis. Association with bronchitis before 2 yr of age and parental asthma was less but significant. PMID- 8484619 TI - Role of arachidonic acid metabolites in airway responses induced by trimellitic anhydride in actively sensitized guinea pigs. AB - We studied the role of arachidonic acid metabolites, histamine, and 5-HT in airway responses to trimellitic anhydride (TMA) in actively sensitized guinea pigs. Sensitization was produced by two intradermal injections of free TMA (0.1 ml of 0.3% TMA in corn oil). After 21 to 28 days, guinea pigs were anesthetized and challenged with intratracheal instillation of 0.5% TMA conjugated to guinea pig serum albumin (TMA-GPSA; 50 microliters). Lung resistance (RL) was measured to assess airflow obstruction, and the tissue content of Evans blue dye was measured to assess airway plasma exudation. Before challenge, sensitized animals were pretreated intravenously with inhibitors of different mediators: pyrilamine (antihistamine: 2 mg/kg, indomethacin (cyclooxygenase inhibitor: 10 mg/kg), OKY 046 (thromboxane synthetase inhibitor: 30 mg/kg), ICI-198,615 (leukotriene receptor antagonist: 10(-6) mol/kg), ketanserin (5-HT2 receptor antagonist: 1 mg/kg), or azelastine ("antiallergic agent": 1 mg/kg). Intratracheal instillation of TMA-GPSA induced a slowly progressing increase in RL and produced extravasation of Evans blue dye at all airway levels in sensitized animals. Pyrilamine and azelastine abolished the increase in RL induced by TMA-GPSA until 2.5 min after the challenge. Indomethacin and OKY-046 significantly attenuated the increase in RL 3 min after the challenge. ICI-198,615 and ketanserin did not significantly affect the increase in RL. Extravasation of Evans blue dye induced by TMA-GPSA was decreased by pyrilamine, azelastine and ICI-198,615 in main bronchi and intrapulmonary airways. Indomethacin, OKY-046 and ketanserin did not significantly affect the extravasation of dye into the airway tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484620 TI - Cellular and biochemical analysis of induced sputum from asthmatic and from healthy subjects. AB - To determine the feasibility of cellular and biochemical analysis of sputum induced after inhalation of hypertonic (3%) saline, we analyzed sputum induced in 10 healthy and in 18 asthmatic subjects. We also analyzed saliva samples from all subjects. The entire sputum sample and the saliva sample were reduced using dithiothreitol, and cell counts and differentials were determined. Biochemical analysis was performed on sputum and saliva supernatants obtained after centrifugation. We found that induced sputum from asthmatic subjects had a higher percentage of eosinophils [8.1 +/- 3.43 (mean +/- SEM) versus 0.03 +/- 0.02%, p < 0.009] (after excluding squamous cells) and also had higher levels of albumin (232.3 +/- 54.8 versus 79.5 +/- 9.7 micrograms/ml, p < 0.02), fibrinogen (44.2 +/ 11.6 versus 11.9 +/- 2.5 micrograms/ml, p < 0.008) and eosinophil cationic protein (ECP) (142.6 +/- 34.2 versus 26.1 +/- 4.7 ng/ml, p < 0.006) but not of histamine or tryptase. In saliva, squamous cells made up more than 99% of the cells in both groups, and protein concentrations were not significantly different. We conclude that cellular and biochemical analysis of induced sputum is feasible in healthy and in asthmatic subjects and that it reveals differences similar to those reported from analyses of bronchial lavage fluid. PMID- 8484621 TI - Markers of mucus secretion and DNA levels in induced sputum from asthmatic and from healthy subjects. AB - To determine whether markers of mucus secretion can be quantified in airway lining fluid from asthmatic and from healthy subjects, we measured levels of a mucin-like glycoprotein (MLG) and lactoferrin in sputum induced by inhalation of hypertonic (3%) saline in 18 asthmatic and in 10 healthy subjects. Because DNA, like mucin, contributes to the viscosity of airway secretions, we also measured DNA levels in the induced sputum samples. To control for the presence of saliva in sputum, we also analyzed saliva samples from all subjects. The entire sputum sample and the saliva sample were reduced using dithiotreitol, and biochemical analysis was performed on supernatants obtained after centrifugation. We found that induced sputum from asthmatic subjects had higher levels of MLG [2,574.4 +/- 907.8 (mean +/- SEM) versus 562.2 +/- 90.5 micrograms/ml, p < 0.007] and DNA (7.1 +/- 1.6 versus 3.6 +/- 0.6 micrograms/ml, p < 0.05), but the difference in lactoferrin levels failed to reach statistical significance. However, in the subgroup of asthmatic subjects who gave a history of sputum production (n = 9), lactoferrin levels were higher than in the healthy control subjects (118.9 +/- 46.3 versus 35.2 +/- 6.5 micrograms/ml, p < 0.05). The very low levels of MLG, DNA, and lactoferrin measured in saliva were not significantly different in asthmatic subjects from those in healthy subjects. We conclude that measurement of markers of mucus secretion in induced sputum is feasible in asthmatic and healthy subjects, and it reveals abnormally high markers of mucus secretion in subjects with stable asthma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484622 TI - Dietary fish oil effects on seasonal hay fever and asthma in pollen-sensitive subjects. AB - The effects of taking 18 capsules a day of Max-EPA (3.2 g/day eicosapentaenoic acid) on clinical symptoms and bronchial hyperresponsiveness were studied in pollen-sensitive subjects over a pollen season in a parallel, double-blind, placebo-controlled (olive oil) fashion. The study was conducted over the 1990 and 1991 pollen seasons in London, England. A total of 37 nonsmoking pollen-sensitive asthmatic subjects were entered into the trial, and 25 completed the 6-month study period over the 2 yr. The preseasonal geometric mean PD35 SGaw of histamine for the fish oil (n = 12) and placebo (n = 9) groups were 0.62 and 0.42 mumol, respectively. During the middle of the pollen season, histamine PD35 SGaw fell significantly for both the fish oil (0.11 mumol, p < 0.0001) and placebo groups (0.10 mumol, p < 0.007), indicating increased bronchial reactivity compared with preseasonal values, but there was no significant difference between the groups. Similarly, morning and evening peak expiratory flow (PEF), diurnal variability in PEF, nocturnal cough and wheeze, daytime wheeze, and activity, as well as nasal symptoms and increased usage of medication, were not significantly different between the groups. Compliance was confirmed by neutrophil and plasma phospholipid analysis, which showed significant rises in eicosapentaenoic acid content in the fish oil group but not in the placebo group. We conclude that dietary fish oil supplementation does not prevent seasonal hay fever and asthma in pollen-sensitive subjects during the pollen season. PMID- 8484623 TI - Effect of electrical stimulation of the hypoglossal nerve on airflow mechanics in the isolated upper airway. AB - To determine the influence of electrical hypoglossal (HG) nerve stimulation on upper airway airflow mechanics, we analyzed pressure-flow relationships obtained during bilateral supramaximal HG nerve stimulation over a range of frequencies from 0 to 100 Hz in the isolated feline upper airway. Inspiratory airflow (VI), hypopharyngeal pressure (Php), and pharyngeal pressure (Pph) immediately upstream from the flow-limiting site (FLS) were recorded while Php was rapidly lowered to achieve inspiratory flow limitation in the isolated upper airway. Pressure-flow relationships were analyzed to determine the maximum in VI (VImax) and the mechanical determinants of VImax, the upper airway critical pressure (Pcrit) and the nasal resistance (RN) upstream to the FLS. In groups of decerebrate spinally anesthetized (n = 6) and unanesthetized (n = 6) cats, graded increases in VImax (p < 0.05) and decreases in Pcrit (p < 0.001) were observed as the stimulation frequency of the intact HG nerves was increased. In the cats with and without spinal anesthesia, VImax increased by 139 and 201%, and Pcrit decreased by 159 and 280%, respectively. RN was also correlated with stimulation frequency in the cats without spinal anesthesia (p = 0.01) and increased in four of six cats with spinal anesthesia. In an additional six decerebrate cats, significant increases in VImax (p < 0.001) and decreases in Pcrit (p = 0.01) were elicited by stimulating the distal cut HG nerve ends (50 Hz), whereas no changes were noted in these parameters when the proximal ends were stimulated. The findings suggest that HG stimulation increases VImax by decreasing Pcrit, which indicates a decrease in upper airway collapsibility at the FLS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484624 TI - Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. AB - Prevalence and characteristics of nutritional depletion were established by body composition measurements in 255 COPD patients in stable clinical condition admitted to a pulmonary rehabilitation center. Depletion of body weight, fat-free mass (using bioelectrical resistance measurements), and muscle mass [from creatinine height index (CHI) and midarm muscle circumference] was most pronounced (40 to 50%) in patients suffering from chronic hypoxemia and in normoxemic patients with severe airflow obstruction (FEV1 < 35%) but also occurred in +/- 25% of patients with moderate airflow obstruction. Classification of the patients in four groups by body weight and fat-free mass revealed that depletion of fat-free mass may occur in normal-weight COPD patients (Group 3). These patients also exhibit a decreased CHI (61 +/- 21%, mean +/- SD) and suffer from physical impairment (12-min walking distance, WD, 532 +/- 152 m) to an even greater degree than underweight patients with relative preservation of fat-free mass (Group 2) (CHI = 73 +/- 16%; WD = 744 +/- 233 m). No systematic differences were established between the four groups in serum protein concentrations or medication use. We conclude that fat-free mass is a better indicator of body mass depletion than body weight. Classification of COPD patients by body weight and fat-free mass may have consequences for planning and interpretation of intervention strategies, particularly in Group 2 and 3 patients. PMID- 8484625 TI - Limited contribution of emphysema in advanced chronic obstructive pulmonary disease. AB - Previous studies on autopsy specimens or surgically resected lobes or lungs have reached varying conclusions regarding the importance of small airways disease and emphysema in causing fixed expiratory airflow limitation in patients with chronic obstructive pulmonary disease (COPD). We obtained high resolution CT scans of the lung and lung function in 56 consecutive patients with fixed expiratory airflow limitation. There was poor correlation between CT emphysema score and either FEV1/FVC% (r = -0.36) or FEV1 % predicted (r = -0.20). In only 10 of the 35 patients with FEV1 < 50% predicted, the CT emphysema score was > 40, indicating significant emphysema. A strong negative correlation between diffusing capacity % predicted and diffusing capacity per alveolar volume and CT emphysema score was found only in patients with FEV1 > or = 1 L (r = -0.75, p < 0.0001). Thus, emphysema does not appear to be primarily responsible for expiratory airflow limitation in COPD. A low diffusing capacity may be spuriously misleading in patients with FEV1 < 1 L and no or trivial emphysema. PMID- 8484626 TI - Effects of one night without nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. AB - Nasal continuous positive airway pressure (CPAP) has become the nonsurgical treatment of choice for obstructive sleep apnea syndrome (OSAS). Recent evidence suggests that intermittent use of CPAP by patients is more common than nightly compliance. To determine the consequences of intermittent CPAP use, in terms of a return of sleep-disordered breathing and daytime hypersomnolence, 15 OSAS subjects were evaluated at three times: (1) before CPAP treatment (pretreatment), (2) after 30 to 237 days posttreatment during a night of CPAP use (on CPAP), and (3) during a night without CPAP (off CPAP). Evaluations of sleep-disordered breathing and three domains of hypersomnolence, physiologic sleep tendency, subjective sleepiness, and performance, were accomplished with the respiratory disturbance index (RDI), multiple sleep latency test (MSLT), Stanford sleepiness scale (SSS), and psychomotor vigilance task (PVT), respectively. CPAP use was encouraged and monitored from pretreatment to post-treatment by daily diaries for most subjects and an electronic device for a subset of subjects. As expected, CPAP eliminated apneas and hypopneas, and following the on CPAP night, there were statistically significant improvements in objective measures of sleepiness (MSLT and PVT). Subjective measures of sleepiness and fatigue also showed improvement. Sleeping without CPAP for one night reversed virtually all of the sleep and daytime alertness gains derived from sleeping with CPAP. This occurred despite a statistically significant reduction in the RDI on the night off CPAP (M = 36.8, SD = 28.0 events/h) relative to the pretreatment night (M = 56.6, SD = 24.8 events/h), which may be due to a lessening of the edema of the upper airway following CPAP use.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484627 TI - Adequacy of prescribing positive airway pressure therapy by mask for sleep apnea on the basis of a partial-night trial. AB - We tested the hypothesis that a prescription for positive-pressure therapy (including pressure level, patient-device interface, and positive-pressure modality, e.g., CPAP or BiPAP) for obstructive sleep apnea (OSA) can be developed on the same night as the polysomnographic (PSG) diagnosis is made. Fifty consecutive patients with OSA in whom a partial-night PSG diagnosis was made (PSGD) underwent a therapeutic trial of positive-pressure therapy during the remainder of the night (PSG-PPP). The average apnea index during PSGD was 54.96 +/- 36.3 (mean +/- SD). On a subsequent full-night PSG (PSG-PPF), the prescription was tested. Thirty-one of the 50 patients were satisfactorily treated with CPAP, without variation of the interface during both PSG-PPP and PSG PPF. In these patients the average pressure prescription while receiving PSG-PPF was statistically higher than during PSG-PPP (11.77 +/- 3.6 versus 10.56 +/- 3.6 cm H2O, respectively, p = 0.002). In 14 of these 31 patients (45%) some alteration in pressure requirement was necessary during PSG-PPF. Eleven patients required 2.5 cm H2O higher pressure and three patients required 5 cm H2O higher pressure during PSG-PPF than during PSG-PPP. There was a change of interface across the two therapeutic trials in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484628 TI - Asynchronous chest wall movements during non-rapid eye movement and rapid eye movement sleep in children with bronchopulmonary dysplasia. AB - The aim of this study was to assess whether age-related changes in thoracic shape modify patterns of thoracoabdominal asynchrony (TAA) or applicability of phase angle analysis during sleep in young children with increased respiratory loads. We assessed TAA during polysomnographic monitoring in 14 young children (mean age 32 months, range 19 to 46; mean weight 12.5 kg, range 9.3 to 17) with severe bronchopulmonary dysplasia (BPD). Of the patients 10 were severely enough affected to require tracheostomy. We measured asynchrony of rib cage (RC) and abdominal (AB) movements at midinspiration and the corresponding phase angle from oscillographic recordings during both non-REM and REM sleep. We measured the amplitude of "paradoxical" displacement of either RC or AB during inspiration and expressed this as a percentage of the total displacement of the compartment. Of 9 children who manifested early inspiratory AB paradox during non-REM sleep, 7 showed a figure eight on the Konno-Mead diagram. The magnitude of abdominal paradox during non-REM sleep was significantly positively correlated with age (n = 14, r = 0.68; p < 0.01). Phase angle was significantly negatively correlated with dynamic lung compliance (n = 14, r = -0.66; p < 0.01). During REM sleep, expiratory abdominal muscle activity was abolished and all patients with abdominal paradox "converted" to an open loop with RC paradox during inspiration. Graphic assessment of the Lissajous figure on the Konno-Mead diagram indicated when midinspiratory phase angle analysis did not reflect the severity of TAA and can be used to infer patterns of respiratory muscle recruitment. We conclude that young children manifest patterns of TAA that differ from the early inspiratory RC paradox commonly observed in infants. Comparison of RC-AB loops between non-REM and REM sleep in the same child can assess increased thoracic inspiratory efforts and expiratory muscle activity as potential mechanisms for abdominal paradox, as distinct from diaphragm ineffectiveness. PMID- 8484629 TI - Ventilatory response to exercise in children with congenital central hypoventilation syndrome. AB - The role of the central and peripheral chemoreceptors in the hyperpnea of exercise has been controversial. We studied five children, age 6 to 11 yr, with absent hypercapneic and hypoxic ventilatory responses during wakefulness (congenital central hypoventilation syndrome, CCHS). Each child performed an incremental treadmill exercise test. Maximal oxygen consumption (VO2) and minute ventilation (VE) at maximal exercise were lower than but not significantly different from these values in a group of nine normal control children of similar age, height, and weight (VO2/kg, 33.7 +/- 5.0 versus 45.4 +/- 2.9 ml/kg/min, mean +/- SEM, NS; VE 28.3 +/- 7.3 versus 43.8 +/- 3.9 L/min, NS). Oxygen tension and saturation fell and CO2 tension rose significantly at maximal exercise in CCHS but not in control subjects. In contrast to control subjects, CCHS subjects increased VE largely by increasing respiratory frequency (f) rather than tidal volume (VT). In the oldest child, submaximal exercise tests at 50% VO2, with varying pacing rate, showed a significant positive relation between pacing rate and f, but not VT. Thus, VE was higher at the faster pacing rate. Further incremental testing in the two oldest subjects with recording of the pacing rate showed positive linear relations between pacing frequency and breathing frequency and between pacing frequency and VE up to a maximum pacing rate of 48 to 50 paces per 15 s. VE beyond this level varied randomly around the maximum level. We conclude that exercise-induced hyperpnea can occur in the absence of chemoreceptor function. In the CCHS children, limb movement is an important determinant of the ventilatory response to exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484630 TI - Dyspnea sensation and chemical control of breathing in adult twins. AB - To examine possible genetic influence on the sensation of dyspnea and on load compensation, we conducted a twin study using healthy adult pairs (10 monozygotes, MZ, and 9 dizygotes, DZ). The ventilatory response to progressive hypercapnia (HCVR) was examined under three different conditions: hyperoxia (PETO2 > 150 mm Hg), hypoxia (PETO2 maintained at 50 to 55 mm Hg), and hyperoxia with an inspiratory flow-resistive load (17 mm H2O/L/s), with simultaneous assessment of the dyspnea sensation by visual analog scale (VAS). Although the VDZ/VMZ ratio (VMZ and VDZ are within-pair variances in MZ and DZ, respectively) for the slope value of the minute ventilation-PETCO2 regression line was not different from 1 in hyperoxia either with or without an inspiratory load, it was significantly larger than 1 in hypoxia (F = 5.17, p < 0.05), suggesting that a genetic influence on HCVR existed only in the presence of hypoxia. During 3% CO2 inhalation, the VDZ/VMZ ratio for the tidal volume (VT) was larger than 1 in hyperoxic HCVR with loading (F = 7.89, p < 0.01), and that for respiratory frequency (f) was larger than 1 only in hypoxic HCVR (F = 3.59, p < 0.05). At a PETCO2 of 55 mm Hg, the VT ratio was larger than 1 under all conditions (F = 5.91, p < 0.05; F = 6.99, p < 0.05; F = 3.75, p < 0.05; respectively), and the f ratio was significantly larger than 1 again only in hypoxic HCVR (F = 3.48, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484631 TI - Speech breathing in patients with lung disease. AB - Lung volumes and breathing patterns used during speech differ from those of quiet respiration and may be expected to vary with different types of lung disease. To test this possibility, 41 patients with asthma, emphysema, or sarcoidosis and 16 healthy subjects completed a speech protocol. Volumes, times, and flow rates were recorded during conversation and during a counting task. A total of 16 measured variables were derived for each breath and analyzed statistically. Alterations in speech breathing were disease and task specific. Discriminant function analysis applied to data from either speech task could correctly classify subjects with more than 50% accuracy, showing that different patterns were significantly disease specific. Compared with healthy subjects during conversation, all patients averaged a more rapid respiratory rate and increased the proportion of time spent on inspiration (Ti/Ttot). During counting, patient groups showed a variety of patterns, most commonly subordinating metabolic need to communication drive and sounding more breathless to observers. Regression analysis was used to determine how strongly changes in measured speech variables related to degree of physiologic impairment. The effect of severity of disease on speech production is distinguishable from the effect of the diagnostic category. PMID- 8484632 TI - Transtracheal delivery of gas decreases the oxygen cost of breathing. AB - Transtracheally administered gases decrease inspired minute ventilation in both dogs and humans. To test if this is associated with a decrease in the oxygen cost of breathing and to evaluate subsequent changes in the breathing pattern, we studied five patients with chronic respiratory diseases while they spontaneously breathed air and different flows of tracheally administered gases. In a blinded crossover design, the gas consisted of either oxygen or air at 2, 4, and 6 L/min. Oxygen cost of breathing was estimated by the calculation of pleural pressure time index (PPTI). The pattern of breathing was evaluated utilizing the tension time index for the diaphragm (TTdi). There were significant decreases in PPTI when the patients received 2, 4, and 6 L/min of transtracheal oxygen or air. TTdi also decreased as gas flow increased. This drop was significant at 6 L/min flow for both gases. We conclude that transtracheally administered gas reduces the oxygen cost of breathing. It also changes the respiratory pattern of the diaphragm to a less demanding pattern. This may offer an alternative form of treatment to rest overworked respiratory muscles. PMID- 8484633 TI - Distribution of asbestos bodies in the human lung as determined by bronchoalveolar lavage. AB - Asbestos-related lung diseases tend to have distinct local distributions, for example, asbestosis first appears and tends to be more severe in the peripheral parts of the lower lung zones. The risk for asbestosis is related to the total asbestos burden of the lung. This suggests that the lower lobes in asbestos exposed individuals may contain more asbestos than the other lobes. To test whether such topographic differences exist, we compared the number of retrieved asbestos bodies (AB) per ml BAL fluid in three groups of occupationally asbestos exposed subjects who underwent BAL at different sampling sites. In Group 1 (n = 24) we performed BAL at three sites, namely in a segment of the right upper, right middle, and right lower lobe, to evaluate differences in asbestos body burden from lung apex to basis. There was a distinct increase in BAL asbestos body concentrations from the upper (21.2 +/- 9.1 AB/ml BAL fluid) to the middle (30.4 +/- 12.8 AB/ml BAL fluid) and to the lower lobe (56.0 +/- 20.2 AB/ml BAL fluid), all differences being significant (p < 0.01). In Group 2 (n = 40), we found good interlobar correlations for asbestos body counts between the right middle lobe (21.0 +/- 5.8 AB/ml BAL fluid) and the lingula (22.4 +/- 5.9 AB/ml BAL fluid) (r = 0.941, p < 0.001) and, in Group 3 (n = 15), between the ventral basal segment of the right (41.2 +/- 13.6 AB/ml BAL fluid) and left lung (39.0 +/ 13.6 AB/ml BAL fluid) (r = 0.966, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484634 TI - Single-cycle bronchoalveolar lavage to determine solute concentrations in epithelial lining fluid. AB - An accurate and reproducible measure of solute concentration of lung epithelial lining fluid (ELF) by bronchoalveolar lavage would be valuable in lung research and in patient care. Measurements of the albumin/total protein ratio in a previously proposed rewash lavage procedure showed that albumin enters the lavage fluid. Therefore, the rewash lavage may measure ELF volume accurately, but it overestimates ELF protein concentration (PELF). To avoid problems of solute exchange, we examined five sequential fractions of lavage fluid obtained from sheep after a single 60-ml lavage containing a 99mTcO4- tracer. Assays of albumin, 99mTcO4-, total protein, and endogenous urea concentrations allowed calculation of PELF from each fraction. PELF was 8 +/- 4 mg/ml when calculated from dilution of either endogenous urea or 99mTcO4- in fractions collected after the first 15 to 20 ml. Paired lavages provided a reproducible measure of PELF (SD, 1.2 mg/ml) that was unaffected by any solute exchange that occurred during the 40-s procedure. Accuracy was verified by comparisons of lung lymph and ELF protein concentrations during high pressure lung edema in anesthetized sheep. The single-cycle lavage procedure is an accurate and reproducible procedure for measuring PELF. PMID- 8484635 TI - The effects of combined histamine and platelet-activating factor antagonism on systemic anaphylaxis induced by immunoglobulin E in the rabbit. AB - Of the mediators released during IgE-induced allergic reactions, it is not known which have the greatest physiologic import in systemic anaphylactic responses. This study describes the effects of histamine and platelet-activating factor (PAF) antagonism (combined) on IgE-induced systemic anaphylaxis in the rabbit. Pretreatment with 30 mumol/kg chlorpheniramine and 30 mumol/kg cimetidine with (Ch/Ci/WEB group) or without (Ch/Ci group) 2.2 mumol/kg of the PAF antagonist WEB 2086 inhibited the anaphylactic alterations in right ventricular pressure, total pulmonary resistance, and decrease in dynamic compliance but not systemic hypotension. Lethality was inhibited only in the Ch/Ci/WEB group. Because previous studies had shown WEB 2086 alone could inhibit the increase in pulmonary resistance, specificity studies were done to determine if WEB 2086 affected histamine activity or release. Responses to intravenously administered histamine (0.54 mumol/kg) were unaffected by WEB 2086 (13.1 mumol/kg). Also, WEB 2086 did not inhibit in vitro antigen-induced basophil degranulation. Thus, the decrease in dynamic compliance and pulmonary hypertension in IgE anaphylaxis appear to be mediated primarily by histamine and the increase in pulmonary resistance by histamine and/or PAF, whereas lethality appears to involve PAF. Some alterations, most notably systemic hypotension, likely involve other allergic mediators. PMID- 8484636 TI - Adrenergic modulation of the pulmonary circulation during strenuous exercise in sheep. AB - In paired experiments, we exercised sheep at a constant rate of 4 mph on a treadmill and measured the hemodynamic effects of alpha receptor blockade (phentolamine 5 mg intravenously), beta receptor blockade (propranolol 1 mg intravenously), and combined alpha and beta receptor blockade. Beta blockade increased pulmonary vascular resistance (PVR) at rest and during steady-state exercise compared with control runs. PVR decreased slightly at rest with alpha blockade, but it was not different during exercise from that of control runs. Combined alpha and beta blockade restored PVR to that of control runs, showing that the vasoconstrictor effect of beta blockade was due to unopposed alpha receptor activation. In all sheep an early rapid decrease in PVR within the first 20 s of the onset of exercise was followed by a smaller, slower change over the next 40 to 240 s. The early decrease in PVR was unaffected by either alpha or beta receptor blockade, suggesting that it was due to recruitment of nonmuscular microvessels. We conclude that alpha and beta receptor activation occurs during exercise but that the net vasoactive effect is neutral. The changes in PVR during normal exercise are a combination of rapid recruitment of microvessels followed by slower vasodilation of resistance vessels. PMID- 8484637 TI - Operation Everest. II: Spirometric and radiographic changes in acclimatized humans at simulated high altitudes. AB - We report spirometry and radiographic data on eight normal male human subjects during prolonged graded altitude exposure to as high as 8,848 m above sea level in a hypobaric chamber. We found a significant and progressive drop in FVC by 14 +/- 3% over 40 days, which resolved slowly during the first 48 h after descent. With altitude, midrange forced expiratory flow (FEF25-75) increased by 82 +/- 3%, probably because of reduced air density. FEV1, however, did not change. Chest radiographs on subjects taken 2 h after descent to sea level showed a pattern of pulmonary artery enlargement and interstitial edema. These data suggest that increased pulmonary blood volume and edema may be causes of the restricted pulmonary function pattern. PMID- 8484638 TI - Evaluation of a new ambulatory spirometer for measuring forced expiratory volume in one second and peak expiratory flow rate. AB - A new pocket-sized ambulatory spirometer (meter) that measures FEV1 and PEFR was evaluated. The meter determines flow rate (V) from the differential pressure (P1 P2) across a sharp-edged orifice (V alpha square root of[P1-P2]). Ten meters were evaluated for accuracy using a computerized syringe to deliver the 24 ATS recommended waveforms and nine scaled versions of a single waveform (PW#24). Within-meter reproducibility of FEV1 and PEFR was evaluated in two meters by passing five versions of waveform PW#24 through each meter 10 times. Reliability in the ambulatory setting was assessed in six meters on several occasions over a 10-week period using five versions of waveform PW#24. Results show that the 10 meters conform to the ATS accuracy specifications for PEFR with one or less errors and marginally outside these limits for FEV1 with four errors. For the nine versions of PW#24, the 95% confidence intervals indicate that the meter is accurate to within +/- 5.5% or +/- 15 L/min for PEFR and +/- 3.5% or +/- 0.12 L for FEV1. The mean within-meter coefficient of variation was 1.24% for FEV1 and 0.35% for PEFR. There was no significant change in meter accuracy or performance over the 10-wk reliability study. We conclude that the meter is suitable for use as an ambulatory spirometer for measuring FEV1 and PEFR. PMID- 8484639 TI - Comparison of the Wang 19-gauge and 22-gauge needles in the mediastinal staging of lung cancer. AB - Transbronchial needle aspiration (TBNA) offers the unique opportunity to pathologically stage patients with lung cancer at the time of diagnostic bronchoscopy. The purpose of this study was to compare the staging sensitivities of the Wang 22-gauge and 19-gauge needles. We studied 64 patients with bronchogenic carcinoma and mediastinal adenopathy. Before bronchoscopy each patient underwent chest CT. Three to four aspirates were obtained with each needle from endotracheal sites adjacent to paratracheal lymphadenopathy. In 47 patients malignant mediastinal adenopathy was confirmed by the 19-gauge needle. A total of 29 patients had malignant 22-gauge needle aspirates. Of the 64 patients, 9 had benign, reactive mediastinal lymph nodes. There were 20 patients in whom only the 19-gauge needle demonstrated malignancy and 2 patients with malignant 22 gauge needle aspirates as the sole identifier of paratracheal malignancy. As a staging tool, the 19-gauge needle was significantly more sensitive than the 22 gauge needle, 85.5 versus 52.7% (p = 0.0001). Overall, in 49 of 55 patients (89.1%) with malignant mediastinal lymphadenopathy paratracheal tumor was confirmed by TBNA. The 19-gauge TBNA staging of the mediastinum is an effective, safe, and cost-saving alternative to surgical mediastinal exploration that can be performed during initial diagnostic bronchoscopy. PMID- 8484640 TI - Peripolesis in alveolar sarcoidosis. AB - We observed that in bronchoalveolar lavages (BAL) of patients with active sarcoidosis (SARC) a mononuclear cell infiltrate is present that often contains clusters consisting of lymphocytes adhering to a macrophage. In order to investigate what kind of cellular interactions are involved in such a process, cell suspensions obtained from BAL of patients with SARC or extrinsic allergic alveolitis (EAA) were cultured for 1 to 2 days, during which time lapse cinematography was applied. We were able to show that such clusters consist of lymphocytes gathered around a macrophage. This is known as peripolesis. Peripolesis, as observed in our BAL, could last for some minutes or for some hours during which time a number of lymphocytes were moving around a single alveolar macrophage, without losing contact with the macrophage. Short interactions were mostly observed in EAA, whereas SARC was characterized by long periods of lymphocyte-macrophage cooperation. We also found a correlation between the time-dependent peripolesis t > 30 min/t < 30 min and the CD4/CD8 ratio. Although the precise mechanisms of peripolesis are not well understood, some interactions between lymphocytes and macrophages have now become more comprehensive. PMID- 8484641 TI - Pulmonary drug toxicity in patients with primary breast cancer treated with high dose combination chemotherapy and autologous bone marrow transplantation. AB - A protocol consisting of standard-dose adjuvant chemotherapy, high-dose combination alkylating agent chemotherapy, and autologous bone marrow transplant (ABMT) used at our institution for patients with primary breast cancer and extensive axillary lymph node involvement has been associated with a clinical syndrome of pulmonary drug toxicity in 23 of 59 patients (39%). In 10 patients in whom open-lung biopsies or transbronchial lung biopsies were obtained, we correlated the pulmonary pathology with the clinical features of the syndrome. These 10 patients presented with dyspnea, cough, fever, and hypoxemia at a mean time of 48 +/- 14 days after initiation of high-dose chemotherapy. Chest radiographs and CT scans showed interstitial and alveolar opacities. Pulmonary function tests revealed restrictive lung disease and reduced diffusing capacities. Open-lung and transbronchial lung biopsies showed alveolar septal thickening with fibrosis, atypical Type II pneumocytes, and pulmonary endothelial cell injury characteristic of drug toxicity. Corticosteroid therapy resulted in clinical improvement in 7 of 10 patients, but significant pulmonary function abnormalities remained. Local radiation therapy to the chest wall and regional lymph nodes appeared to exacerbate preexisting pulmonary drug toxicity in 4 patients. Two agents in the protocol, cyclophosphamide and carmustine (BCNU), can be implicated in the pathogenesis of this syndrome, and these agents most likely act synergistically to deplete reduced glutathione and impair antioxidant defenses. Since these drugs appear to contribute to the protocol in prolonging disease-free survival, prophylactic therapy of the lung should be investigated to reduce the high incidence of pulmonary toxicity. PMID- 8484642 TI - Clinical features of pulmonary disease caused by rapidly growing mycobacteria. An analysis of 154 patients. AB - The role of rapidly growing mycobacteria (RGM) as pulmonary pathogens has been unclear. We identified 154 cases of lung disease caused by RGM using the microbiologic and radiographic criteria of the American Thoracic Society (ATS) and availability of the causative organism for study. More than one third of patients had positive lung biopsy cultures. Patients were predominantly white (83%), female (65%) nonsmokers (66%), and they had prolonged periods from onset of symptoms to diagnosis of their disease. Cough was an almost universal presenting symptom, whereas constitutional symptoms became more important with progression of disease. Upper lobe infiltrates were most common (88%), with 77% of patients developing bilateral disease. Cavitation was present in only 16% of the patients. Specific underlying diseases were infrequent, but they included previously treated mycobacterial disease (18%), coexistent Mycobacterium avium complex (8%), cystic fibrosis (6%), and gastroesophageal disorders with chronic vomiting (6%). The majority of isolates (82%) were M. abscessus (formerly M. chelonae subsp. abscessus). Effective treatment for M. fortuitum long disease was accomplished with drug therapy, whereas surgical resection of localized disease was the only effective long-term therapy for M. abscessus. Although the disease was generally slowly progressive, 21 of 154 (14%) patients died as a consequence of progressive RGM lung disease and respiratory failure. RGM should be recognized as a cause of chronic mycobacterial lung disease, and respiratory isolates should be assessed carefully. PMID- 8484643 TI - Lung distribution and pharmacokinetics of aerosolized tobramycin. AB - Aminoglycosides are commonly used in the treatment of nosocomial pneumonia in association with beta-lactams. Unfortunately, penetration of intravenously administered aminoglycosides into the lung tissue remains low. In animal models, aerosolization of these drugs provides high lung concentrations and low serum levels. Three-hundred milligrams of tobramycin and 1 ml of 99mTc-DTPA were administered via a pneumatic nebulizer to five healthy volunteers and to five mechanically ventilated patients. Lung scintigraphy was then performed, and plasma and urine pharmacokinetics were studied. In a second group of patients undergoing thoracic surgery, 300 mg of tobramycin alone were administered in the same way; a fragment of healthy lung was then removed, and tobramycin was measured. In the first group, the scintigraphy showed radioactivity distribution in the whole lungs both in healthy volunteers and in ventilated patients. Urine samples contained 5.5% of the initial amount of tobramycin. The mean serum half life of tobramycin was 8.96 h in healthy volunteers and 11.23 h in ventilated patients. In the second group, mean lung tissue concentrations were 5.5 and 3.61 micrograms/g, respectively, 4 and 12 h after nebulization, respectively. Aerosolization of tobramycin thus produced high lung concentrations and low serum levels. PMID- 8484644 TI - HIV testing in patients with tuberculosis. Physician response to national recommendations. AB - The epidemic of human immunodeficiency virus (HIV) disease has contributed to the resurgence of tuberculosis in the United States. For clinical and public health reasons, the Advisory Council for the Elimination of Tuberculosis has recommended that all patients with tuberculosis be tested for HIV antibodies. We reviewed the medical records of all patients with tuberculosis in whom a diagnosis was made at a Detroit medical center from July 1, 1986 to June 30, 1990, before and after recommendations were issued. Of 195 patients, 69 (35.4%) were tested for HIV antibodies: 73.7% of 57 patients whose medical records documented risk behaviors for HIV infection, and 19.6% of 138 patients who denied high-risk behaviors or whose medical records contained no risk information (relative risk of testing among patients with documented risk factors compared with others, 3.8; 95% confidence interval, 2.6 to 5.5). Testing of patients who denied risk behaviors or had no information in their records increased from 14.9% in the first 12 months to 30.4% in the last (p = 0.08, test for trend). In this population, national recommendations appear to have stimulated HIV testing, although most patients still are not being tested. PMID- 8484645 TI - Comparison of the Raja and the Abrams pleural biopsy needles in patients with pleural effusion. AB - In 31 patients with exudative pleural effusions, we compared the diagnostic yield of the Abrams pleural biopsy needle with that of a new instrument, the Raja pleural biopsy needle. Each patient was randomly biopsied with both needles, and a total of 153 pleural biopsies were done, 73 with the Abrams needle and 80 with the Raja needle. No complications resulted from biopsies with either needle. Etiologic diagnoses were possible in 38 (52%) biopsies obtained using the Abrams needle, compared with 66 (82.5%) for those using the Raja needle; the difference in proportions for the diagnostic yield was statistically significant (p < 0.01, two-tailed Fisher's exact test). There were no significant differences between the needles in obtaining etiologic diagnoses in any specific disease category. The difference between the mean size of the pleural specimens obtained with the two needles was also statistically significant (p < 0.001, Mann-Whitney U test). The Raja pleural biopsy needle is easy and safe to use, and despite its smaller external diameter yields a significantly larger pleural tissue sample and significantly increases the diagnostic yield of pleural biopsies compared with the Abrams pleural biopsy needle. PMID- 8484646 TI - PEEP does not improve pulmonary mechanics in infants with bronchiolitis. AB - Positive end-expiratory pressure (PEEP) may improve pulmonary mechanics, work of breathing, and gas exchange in some patients with respiratory failure. These beneficial effects do not occur consistently, however, and side effects, such as gas trapping due to expiratory flow limitation, may be exacerbated. We determined the effects of PEEP (0, 3, 6, and 9 cm H2O applied in random order) on the expiratory airway resistance and static compliance of nine infants mechanically ventilated for acute bronchiolitis. We also noted the presence of inadvertent PEEP (PEEPi) to determine its influence on the response to applied PEEP. Applied PEEP at any level failed to consistently improve passive expiratory airway resistance or increase compliance from baseline (PEEP = 0 cm H2O, resistance = 92 +/- 32 cm H2O/L/s; compliance = 0.71 +/- 0.19 ml/cm H2O/kg). Increases in end expiratory lung volumes ranged from 18 to 40% of the tidal volume at maximal PEEP. Although all infants had PEEPi (5 +/- 2 cm H2O), PEEPi had no influence on the response of mechanics to applied PEEP other than that peak inspiratory pressures increased when PEEP > PEEPi. We conclude that the routine use of PEEP in infants with bronchiolitis does not consistently improve passive expiratory pulmonary mechanics and may increase the risk of barotrauma from gas trapping. PMID- 8484647 TI - Silicone fluid-induced pulmonary embolism. AB - Silicone fluid injection for mammary augmentation is a well-known illegal procedure. It has been associated with many complications, including local tissue granulomatous reaction, chronic infection, and sclerosis, but pulmonary involvement in human beings has been documented in only six cases. We describe three more such cases of pulmonary embolism. These three patients were all female, young, and previously healthy. They received the procedures only for cosmetic reasons. Unfortunately, one of them died and another lived with the sequelae of pulmonary fibrosis. The mortality rate of the nine total patients with pulmonary embolism induced by silicone fluid, including our three cases, is 33%. Because of this high mortality rate and long-term sequelae of pulmonary fibrosis, no silicone fluid injection should be given for cosmetic reasons, especially in mammary augmentation in which a large volume of silicone fluid is more likely to be used, and the early use of corticosteroid therapy may be helpful. PMID- 8484648 TI - Nortriptyline-induced depression of ventilatory control in a patient with chronic obstructive pulmonary disease. AB - Psychiatric disorders occur frequently in patients with COPD, but therapy with psychotropic drugs is often limited by concomitant depression of ventilatory drive. We present a patient with COPD and major depression who developed hypercapnic respiratory failure while receiving nortriptyline and oxazepam. Because of known respiratory depressant effects of the latter drug, nortriptyline alone was resumed upon recovery. Depression of CO2 sensitivity and ventilatory load compensation with a concomitant increase in exercise tolerance with decreased dyspnea was observed while she was receiving nortriptyline. These results demonstrate a previously unreported depressant effect of nortriptyline on ventilatory control, and they suggest the need for further investigation of the ventilatory effects of this drug in patients with pulmonary disease. PMID- 8484649 TI - Dosages of corticosteroids in asthma. PMID- 8484650 TI - When tuberculosis treatment fails. A social behavioral account of patient adherence. AB - Several conclusions about measuring adherence can be drawn. Probably the best approach is to use multiple measures, including some combination of urine assays, pill counts, and detailed patient interviews. Careful monitoring of patient behavior early in the regimen will help predict whether adherence is likely to be a problem. Microelectronic devices in pill boxes or bottle caps have been used for measuring adherence among patients with tuberculosis, but their effectiveness has not been established. The use of these devices may be particularly troublesome for some groups such as the elderly, or precluded for those whose life styles might interfere with their use such as the homeless or migrant farm workers. Carefully designed patient interviews should be tested to determine whether they can be used to predict adherence. Probably the best predictor of adherence is the patient's previous history of adherence. However, adherence is not a personality trait, but a task-specific behavior. For example, someone who misses many doses of antituberculosis medication may successfully use prescribed eye drops or follow dietary recommendations. Providers need to monitor adherence to antituberculosis medications early in treatment in order to anticipate future problems and to ask patients about specific adherence tasks. Ongoing monitoring is essential for patients taking medicine for active tuberculosis. These patients typically feel well after a few weeks and either may believe that the drugs are no longer necessary or may forget to take medication because there are no longer physical cues of illness. Demographic factors, though easy to measure, do not predict adherence well. Tending to be surrogates for other causal factors, they are not amenable to interventions for behavior change. Placing emphasis on demographic characteristics may lead to discriminatory practices. Patients with social support networks have been more adherent in some studies, and patients who believe in the seriousness of their problems with tuberculosis are more likely to be adherent. Additional research on adherence predictors is needed, but it should reflect the complexity of the problem. This research requires a theory-based approach, which has been essentially missing from studies on adherence and tuberculosis. Research also needs to target predictors for specific groups of patients. There is clear evidence of the effect on adherence of culturally influenced beliefs and attitudes about tuberculosis and its treatment. Cultural factors are associated with misinformation about the medical aspects of the disease and the stigmatization of persons with tuberculosis. Culturally sensitive, targeted information is needed, and some has been developed by local tuberculosis programs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8484651 TI - Bacteriology of ventilator-associated pneumonia. PMID- 8484652 TI - Aspergillus epidural abscess and cord compression in a patient with aspergilloma and empyema. PMID- 8484653 TI - The triplex hypothesis of vision. AB - The duplex theory of vision is concerned with the light level and dual retinal function and refers only to the rod and cone photoreceptor cell systems. There are some visual functions that are not represented by the duplex theory, visual field, or the dark-adaptation curve. There is some confusion as to whether the relationship between visual threshold and bleached pigment is logarithmic or linear. I do not know how many photopigments exist and which pigment and what circuit plays a role in the photoperiod. The complexity of the retina appears to exceed its known functions. Finally, I wonder how the rate of eye growth is regulated. To clarify these concerns, I propose a new cell type and a third mechanism of vision, which has not been described previously to my knowledge. On the basis of this study and the data from the literature, it appears that early retinal ganglion cells cannot project into the visual cortex because the latter has not been formed. Therefore, their axons may progress into the diencephalic centers that are developing and are differentiating. So, there is a novel photoreceptive system with its associated ganglion cells that is the basis for the visual foundation. These are the first photoreceptors to form and are not engaged directly in the visual process, but they play a significant role in nutrition, function, and the well-being of the other parts of the visual apparatus. This, of course, requires much investigation and research. I believe there are three classes of photoreceptors and submit the following triplex hypothesis. PMID- 8484654 TI - A comparison of the ocular tolerability of a single dose of timolol and levobunolol in healthy normotensive volunteers. AB - Subject acceptance of a single dose of timolol and levobunolol was compared in a three-center, double-masked, randomized, crossover study in healthy normal subjects. We tested 115 subjects who received the medications OU, in a random order, separated by a washout period of three to seven days. At the end of the administration, the subjects were asked to report any symptoms and were monitored by ophthalmologic examination. Those receiving levobunolol reported a two- to threefold higher frequency of symptoms than did those receiving timolol (P = .0002, by Mainland-Gart chi-square test). Thirty-five subjects (30.4%) treated with levobunolol complained of burning versus 14 (12.2%) receiving timolol (P = .0021). Similar results were obtained in regard to stinging (31 versus 10 subjects; P = .0011). The duration of these symptoms did not differ between the two groups (P > .05). Timolol induced considerably less burning and stinging on day 1 compared with levobunolol, using a visual analog scale over time (P = .0004). Seventy-nine percent of those stating a preference chose timolol (P < 3 x 10(-9). PMID- 8484655 TI - Treatment of diabetic macular edema: a comparison between argon and dye lasers. AB - To compare the efficacy of argon green and dye yellow photocoagulations, 85 eyes of 85 diabetic patients with diffuse macular edema were included in a prospective randomized clinical trial. One year after treatment, visual acuity was unchanged or better in 85.1% of eyes treated with an argon and 89.5% of eyes treated with a dye laser. A reduction of macular edema was accomplished in 67.3% of eyes in the argon-laser group and in 71.1% of eyes in the dye-laser group. No statistically significant differences were observed between the two groups in regard to visual acuity results or the reduction of macular edema. PMID- 8484656 TI - Fatigue effect within 10 degrees visual field in automated perimetry. AB - We studied the effect of fatigue within a 10 degree visual field measured with automated perimetry in normal volunteers (10 eyes), patients who have recovered from optic neuritis with multiple sclerosis (10 eyes), and patients with glaucoma (10 eyes). Using an Octopus 201, the visual field was tested with Program 61, which was centered (0.0), and 25 test locations were determined three times. Eight of the 25 points were selected for the evaluation. The mean sensitivity of the eight points was compared among the three measurements. Normal subjects and patients with optic neuritis showed no effect of fatigue within the 10 degrees visual field, but the patients with glaucoma indicated fatigue during the third measurement. PMID- 8484657 TI - Occlusion therapy of Japanese children with anisometropic amblyopia without strabismus. AB - We examined 38 children (20 boys and 18 girls) with anisometropic amblyopia without strabismus who had been treated with occlusion therapy. At the initial visit, their ages ranged from five to ten years. Their visual acuity scores improved after therapy, and this was unrelated to patient age. The amount of anisometropia, visual acuity at the initial visit, and compliance were related to improved visual acuity in the amblyopic eye. The visual acuity improved for six months after therapy. No further gains were detected thereafter. PMID- 8484658 TI - Conjunctival lymphoid hyperplasia. AB - Our patient had uncommon features of conjunctival lymphoid infiltrates, including patient age, bilaterality, and lesion location. We describe his case and discuss the prognosis based on a literature review. PMID- 8484659 TI - Fluorescein angiographic appearance of Dalen-Fuchs nodules in sympathetic ophthalmia. AB - A case of sympathetic ophthalmia is presented in which a single lesion located posteriorly at the level of the retinal pigment epithelium caused a serous macular detachment. We believe that this lesion represented an atypical Dalen Fuchs nodule. Most reports of the fluorescein angiographic appearance of Dalen Fuchs nodules describe multiple sites of choroidal leakage during the early phases, which may coalesce during the late phases of the angiogram. The lesion we detected was hypofluorescent in early phases of the fluorescein angiogram and showed late staining. The early hypofluorescence seen in the lesion may be explained by an intact retinal pigment epithelium over the presumed Dalen-Fuchs nodule, blockage of choroidal fluorescence by the nodule, and areas of granulomatous inflammation in the inner choroid and choriocapillaris. The staining in the late phases of the fluorescein angiogram may be explained by accumulation of fluorescein into the presumed Dalen-Fuchs nodule. PMID- 8484660 TI - Wasp sting-induced retinal damage. AB - A 36-year-old man was stung by a wasp OD. He became delirious and had dyspnea, ocular pain, and severely decreased visual acuity OD. A broken stinger was found in the central deep cornea. Additional ocular findings were keratitis, iritis, cataract, secondary glaucoma, and unrecordable electroretinographic responses. PMID- 8484661 TI - [Saying what we mean]. PMID- 8484662 TI - [Rehospitalization and early discharge in neonatology: retrospective evaluation]. AB - This retrospective study compared discharge summary data in neonates discharged from the Brest Teaching Hospital Neonatology Unit between May 1, 1980 and April 30, 1981 (Period I) or between May 1, 1990 and April 30, 1991 (Period II). Birth weight, gestational age, duration of hospitalization, corrected age at discharge and rehospitalization rate were compared. Among infants with intrauterine growth retardation (IUGR) with or without prematurity, weight at discharge was 2,500 g or less in none of Period I patients (n = 144) versus 67.8% of Period II patients (n = 87). Four Period II infants weighted 2,000 g or less at discharge (1,850, 1,930, 1,960, and 2,000 g). Among premature infants without growth retardation, weight at discharge was 2,500 g or less in 2.2% of Period I infants versus 52.5% of Period II infants (p < 0.0001). Period II infants were not rehospitalized more often or earlier than Period I infants. Early discharge reduces the duration of separation of the child from his or her parents without increasing the rehospitalization rate. PMID- 8484663 TI - [Lipoma of the corpus callosum. 3 case reports and review of the literature]. AB - Lipoma of the corpus callosum is a rare congenital intracranial tumor. Although only 153 cases had been reported as of March 1992, the incidence of this tumor is underestimated (some cases are unpublished and others are asymptomatic). Three cases of lipoma of the corpus callosum diagnosed in children are reported herein. These tumors may be either discovered fortuitously in an asymptomatic patient or responsible for manifestations of which the most common are seizures, headache, and mental disorders. Diagnosis rests on imaging techniques. The main investigation is computed tomography which discloses a mass composed of fat, with or without peripheral calcifications, and also identifies any other malformations such as dysgenesis of the corpus callosum. PMID- 8484664 TI - [Depression in childhood]. AB - Depressive syndromes occur at any age and require appropriate therapy. Available classifications include the French Classification of Mental Disorders in Children, the Diagnostic and Statistical Manual of Mental Disorders IIIrd edition Revised (DSM-III-R), and the International Classification of Diseases. Prevalence of depression approximates 1% to 3% in children and adults. Recent studies have investigated relationships between depression and anxiety or behavior disorders familial clustering of depression, and adult outcome of depression in children and adolescents. Early onset of major depression (before the age of 20) is an established risk factor for depression in adulthood. Pediatricians may encounter depression in emotionally deprived infants (hospitalism), victims of child abuse, and children who attempt suicide. Concepts concerning major affective disorders are changing; adolescents have specific characteristics regarding symptoms and risk of subsequent relapsing disease. Although biochemical and sleep pattern markers have not as yet been adequately studied in pediatric patients, the clinical efficacy of drug therapy has been established. PMID- 8484665 TI - [The "blue rubber bleb nevus" (Bean's syndrome): uncommon cause of gastrointestinal bleeding]. AB - A ten year old boy had six cutaneous angiomas and recurrent rectal bleeding responsible for iron deficiency anemia. Histological examination established the diagnosis of blue rubber bleb naevus syndrome. Endoscopy, arteriography, computed tomography, and angioscintigraphy disclosed additional angiomas in the stomach and rectum and along the blood vessels in the lower limbs. The value of angioscintigraphy for identifying angiomas escaping detection by other means was illustrated in this case. Embolization of the inferior mesenteric artery was successful in preventing further rectal bleeding. Treatment of this disorder remains controversial. PMID- 8484666 TI - 6th International Conference on Antiviral Research. Venice, Italy, April 25-30, 1993. Abstracts. PMID- 8484667 TI - Assessment of lupus: where are we now? AB - Decisions about treatment for patients with SLE are based on numerous criteria, including the rate of change of clinical features and disease markers (especially antibodies to dsDNA and markers of complement turnover), which organ systems are affected, the severity of manifestations, and the presence of pre-existing damage (which may reduce the reserve capacity of the organ system). Most of the currently available organ systems calculate a single overall score, at a single point in time, and take few of these considerations into account. SLAM is the only index to consider directly the scoring of severity as well as activity, though this concept is probably inherent in most of the other indices because of various methods for weighting the scores. Preliminary studies have indicated that four of the scales (BILAG, SLAM, LAI, and SLEDAI) are sensitive to change. Few of the indices have been tested longitudinally, hence their role in clinical trials remains to be established. None of the indices considers the impact of damage, indeed this is not their remit, but this concept is being considered by an international working group. Outcome in SLE has been shown to be determined by, among other things, the number of exacerbations and the presence of renal or neurological disease. It would seem, therefore, important to measure disease activity in designated organ systems, which most of the indices fail to do. The inclusion of immunological tests in some scales (for example, SIS, SLEDAI, LAI) makes them unsuitable for use as instruments to validate immunological or other scatological markers. Furthermore, given the heterogeneity of disease manifestations in SLE, and evidence linking scatological abnormalities with specific clinical manifestations, it is perhaps naive to expect a new scatological test to correlate strongly with overall disease activity. Three of the currently available activity scales have been shown to be reliable, both between and within raters (BILAG, SLAM, SLEDAI). The lack of a 'gold standard' for measuring disease activity in SLE makes it difficult to be sure that these scales are actually measuring what they are supposed to be measuring (criterion validity), but they do correlate strongly with each other in cross sectional studies, suggesting that they are, at least, all measuring the same thing (convergent validity). Convergent validity for these instruments used longitudinally remains to be established, particularly for patients with very active disease. In conclusion, measurement of disease activity in SLE is central to patient care, and a number of instruments are available fro this purpose. Although none is perfect, most are reliable and valid, and are suitable for classifying and monitoring groups of patients in the research setting. In reality, the indices are used with the additional benefit of laboratory markers and, as yet, no one has found the instruments sufficiently sensitive and specific to rely entirely upon them. The exact choice of instrument should be governed by the purpose for which it is required in clinical practice. Disease activity scales are unlikely to be appropriate for dictating treatment decisions in individual cases. An instrument which would be comprehensive and flexible enough for this purpose would necessarily prove too complicated and cumbersome for widespread use. PMID- 8484668 TI - Mortality and causes of death in 398 patients admitted to hospital with ankylosing spondylitis. AB - The mortality and causes of death in 398 patients (47 women, 351 men) with definite ankylosing spondylitis, admitted to hospital for the first time between 1961 and 1969, were investigated. The mean age at first admission was 36.5 years (SD 11.8). After a mean follow up time of 25.7 years, a total of 152 patients (12 women, 140 men) had died. The expected mortality based on the mortality statistics of the general population of the same sex and age was 103.1 (9.4 women and 93.7 men). Thus the overall mortality of the patients with ankylosing spondylitis was 1.5 times that expected. Those patients who had died were significantly older, had a higher erythrocyte sedimentation rate, and more inflamed peripheral joints when first seen than the surviving patients. The main difference between the observed and expected causes of death was the high incidence of deaths from ankylosing spondylitis, which was the underlying cause of death in 27 patients. The mechanism of death in these patients was secondary amyloidosis in 19, cardiovascular complications in six, fracture of the spine in one, and it was not known in one patient. Excess deaths due to circulatory, gastrointestinal and renal diseases, and violence were also observed. PMID- 8484669 TI - Identification of tissue inhibitor of metalloproteinase-2 (TIMP-2)-progelatinase complex as the third metalloproteinase inhibitor peak in rheumatoid synovial fluid. AB - The metalloproteinases are a family of enzymes that can degrade all the components of the extracellular matrix. These potent enzymes are often found in proenzyme forms and require activation before the substrate can be digested. To prevent unlimited connective tissue destruction a number of inhibitors exist to limit their activity. In a previous study it was found that metalloproteinases in proenzyme form and metalloproteinase inhibitors were often present in rheumatoid synovial fluids. Two of these inhibitors were identified in rheumatoid synovial fluid as alpha 2 macroglobulin and tissue inhibitor of metalloproteinase (TIMP), the specific metalloproteinase inhibitor. A third inhibitory peak was unidentified. In the study reported here it was shown that this third inhibitor can be purified using gelatin-Sepharose chromatography and consists of TIMP-2 bound to progelatinase (relative molecular weight 72,000) in a similar way to that found in concentrated connective tissue culture medium. The importance of these proteinase inhibitors in synovial fluid is discussed. PMID- 8484670 TI - Protection from interleukin 1 induced destruction of articular cartilage by transforming growth factor beta: studies in anatomically intact cartilage in vitro and in vivo. AB - The modulation of interleukin 1 (IL-1) effects on proteoglycan metabolism in intact murine patellar cartilage by transforming growth factor beta (TGF-beta) was investigated in vitro and in vivo. In vitro TGF-beta (400 pmol/l) had no effect on basal proteoglycan degradation. Proteoglycan degradation induced by IL 1, however, was suppressed by TGF-beta in serum free medium alone and in medium supplemented with 0.5 micrograms/ml insulin-like growth factor 1. This suggests a specific regulatory role for TGF-beta under pathological conditions. In contrast with the suppression of breakdown, synthesis of proteoglycans was stimulated by TGF-beta for both basal and IL-1 suppressed proteoglycan synthesis in cultures without insulin-like growth factor. In the presence of insulin-like growth factor no extra effect of TGF-beta on proteoglycan synthesis was observed. With insulin like growth factor, however, TGF-beta potentiated the ex vivo recovery of IL-1 induced suppression of proteoglycan synthesis. Analogous to the in vitro effects, TGF-beta injected intraarticularly suppressed IL-1 induced proteoglycan degradation. Furthermore, TGF-beta injected into the joint counteracted IL-1 induced suppression of proteoglycan synthesis. This indicates that in vivo also TGF-beta can ameliorate the deleterious effects of IL-1 on the cartilage matrix. PMID- 8484671 TI - Altered Golgi apparatus in hydrostatically loaded articular cartilage chondrocytes. AB - OBJECTIVES: Articular cartilage proteoglycan content is controlled by joint loading. This study aimed to elucidate the role of hydrostatic pressure in this regulation. METHODS: Primary cultures of chondrocytes from bovine articular cartilage, grown on coverslips, were subjected to 5, 15, or 30 MPa hydrostatic pressure, applied continuously or cyclically at 0.125 or 0.05 Hz. The Golgi apparatus was visualised either by a fluorochrome coupled wheat germ agglutinin or by transmission electron microscopy. Proteoglycan synthesis was studied by the incorporation of sulphur-35 labelled sulphate. RESULTS: After 30 MPa continuous hydrostatic pressure, the Golgi apparatus was observed in a compact form with a concomitant decrease in proteoglycan synthesis. The normal stacked appearance of the Golgi apparatus was no more visible in the electron microscopy preparation of the pressurised chondrocytes. This effect was reversible and was also noticed after 15 MPa continuous load, though to a minor extent. Cyclic pressures (5-30 MPa) caused no apparent change in the Golgi apparatus. The shape of some cells changed to a more retracted form after 30 MPa continuous pressure. Nocodazole, which causes disassembly of the microtubules, blocked the compacting influence of pressurisation on the Golgi apparatus, and reduced proteoglycan synthesis to about half of the control level. CONCLUSIONS: The packing of the Golgi apparatus is dependent on microtubules and may contribute to the inhibition of proteoglycan synthesis observed in articular cartilage subjected to high hydrostatic pressure. PMID- 8484672 TI - Expression of public idiotypes in patients with Lyme arthritis. AB - OBJECTIVE: Joints are often affected in Lyme disease and in some instances this may be due to immune autoreactivity. To characterise further the immune response in this disease investigations were carried out to determine the expression of three public idiotypes on serum immunoglobulins in patients with Lyme disease during the development of varying degrees of arthritis. METHODS: The expression of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on monoclonal antibodies to DNA, was determined by an enzyme linked immunosorbent assay (ELISA) in serial blood samples from 12 patients with Lyme disease over a mean period of six years during the development of a variety of arthritic symptoms, and in serum samples from healthy control subjects and control subjects with systemic lupus erythematosus. RESULTS: Expression of serum IgM or IgG public Ids 16/6 and BEG2 was significantly increased in patients with Lyme disease. IgA Id 16/6 expression, in contrast, was significantly increased only during episodes of arthritis and was also related to its severity. IgM and IgG Id 16/6 expression was related to their respective total immunoglobulin concentration and, in the case of IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas similar findings were not apparent with IgA antibodies. This may indicate that the IgA response is related to the pathogenesis of arthritis, especially as total IgA and IgA Id 16/6 levels were found to increase over the duration of disease. Sequential analysis of antibodies also showed restriction in the expression of Id 16/6 as it was never found on all immunoglobulin isotypes at the same time, and Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however, may be associated as seven patients expressed these idiotypes simultaneously. CONCLUSIONS: These data indicate the use of public idiotypes in the immune response against B burgdorferi, which may be restricted in terms of idiotype class and isotype expression, and a possible association between IgA antibodies bearing Id 16/6 with arthritis. PMID- 8484673 TI - Rational diagnosis and treatment in unclassified arthritis: how clinical data may guide requests for Lyme serology and antibiotic treatment. AB - To improve the appropriateness and efficiency of diagnostic serological tests and subsequent antibiotic treatment, clinical data from 102 patients with unclassified arthritis were analysed to investigate whether the presence of positive IgG antibodies to Borrelia burgdorferi could be predicted. The clinical data were blindly ranked from 1 to 4 (1, Lyme arthritis unlikely; 4, Lyme arthritis very likely). Antibodies to B burgdorferi were positive in nine of 102 patients (9%). Six of 15 (40%) patients with rank numbers 3 and 4 were positive for antibodies to B burgdorferi, in contrast with only three of 87 (3%) patients with rank numbers 1 and 2. The likelihood ratio of positive Lyme serology for patients ranked 3 and 4 was 12.0, for patients ranked 2 to 4, 4.5, and for patients with arthritis of the knee, 3.0. These likelihood ratios were associated with a post-test probability of 55, 30, and 20% respectively. The clinical history in patients with unclassified arthritis can largely predict the presence of antibodies to B burgdorferi. The absolute value of a likelihood ratio can be a contributing factor in deciding to request tests for antibodies to B burgdorferi in patients with unclassified arthritis. PMID- 8484674 TI - Depressed levels of dehydroepiandrosterone sulphate in postmenopausal women with rheumatoid arthritis but no relation with axial bone density. AB - The sex hormones dehydroepiandrosterone sulphate (DHEAS), oestradiol, and sex hormone binding globulin (SHBG) were measured in 185 postmenopausal women (aged 45-65 years) with rheumatoid arthritis (RA) and related to assessments of bone mineral density at the spine and proximal femur. Compared with 518 postmenopausal control women (aged 45-65 years), DHEAS levels were below normal in the 120 patients with RA who had never taken corticosteroids and levels were further depressed in 39 patients currently using steroids. Twenty six patients who had completed steroid treatment also had lower DHEAS levels, suggesting a delayed recovery of adrenal androgen secretion. Oestradiol and SHBG levels were similar in all groups. There was no correlation between sex hormones and disease activity. Oestradiol correlated with bone mineral density at all sites. Although oestradiol correlated with DHEAS, there was no relation between DHEAS and bone mineral density. The cause of below normal levels of DHEAS in RA is unclear, whether a consequence of chronic illness, immune dysfunction, or a defect of adrenal androgen synthesis. PMID- 8484675 TI - Modified suprascapular nerve block with bupivacaine alone effectively controls chronic shoulder pain in patients with rheumatoid arthritis. AB - Chronic shoulder pain is a common and disabling symptom in patients with rheumatoid arthritis (RA). It has been previously shown that a suprascapular nerve block (SSNB) using the standard mixture of bupivacaine and adrenaline (Ba) plus methylprednisolone (P), which is routinely used in pain clinics, results in a considerable improvement in pain relief and range of movement compared with conventional intra-articular steroid injections in such patients. A double blind study was carried out in 29 patients (58 shoulders) with RA to compare SSNB induced with Ba alone with that induced using the conventional mixture of Ba plus P. Highly significant improvements were noted in measures of pain, stiffness, and range of most movements for both treatments (up to three months) compared with baseline. Results favoured Ba alone; the differences between the two treatments reached statistical significance for stiffness (at 12 weeks) and active abduction (at one week). It is concluded that the addition of P to the SSNB mixture confers no benefit in these patients. PMID- 8484676 TI - Cutaneous manifestations associated with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome: a case-control study. AB - OBJECTIVE: To study the association of a variety of dermatological manifestations related to vascular abnormalities with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome. METHOD: Case-control study. Consecutive patients referred to the coagulation and haemostasis service of a general hospital for the first determination of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and newly diagnosed disorders (for example, thrombocytopenia, thrombotic disorders, and unexplained repeated abortions) were selected. Patients were examined by two dermatologists according to predefined criteria, and information about general characteristics and relevant dermatological and medical histories were collected using an ad hoc questionnaire. The study was limited to patients without evidence of systemic lupus erythematosus. A total of 35 patients was examined; 13 subjects were positive for lupus anticoagulant or anticardiolipin antibodies, or both (cases), and 22 were negative (controls). RESULTS: Moderate to severe livedo reticularis and acrocyanosis were significantly associated with antiphospholipid antibodies, with relative risks of 13.1 (95% confidence interval 1.1 to 149.0) and 8.6 (95% confidence interval 1.1 to 65.1). Capillaritis was also associated with the antibodies. Histories of Raynaud's phenomenon and superficial thrombophlebitis were more common in cases than controls. CONCLUSIONS: This study provides quantitative evidence of the association of antiphospholipid antibodies with several cutaneous diseases in which vascular abnormalities seem to play a major part. The study suggests that these manifestations might appear early in the development of the antiphospholipid syndrome. PMID- 8484677 TI - Yersinia associated arthritis in SHR rats: effect of the microbial status of the host. AB - Following the intravenous injection of live Yersinia enterocolitica O:8, 50-69% of SHR rats developed arthritis; these rats were antibody free against all rat pathogens tested. In contrast, only 20-25% of SHR rats which had serum antibodies against Bacillus piliformis, Kilham rat virus, and Toolan H-1 virus developed arthritis. The results indicate that the microbial load of the host has a profound effect on the susceptibility to experimental arthritis. PMID- 8484678 TI - Levels of insulin related growth factor 1 in osteoarthritis of the knee. AB - OBJECTIVES: Insulin related growth factor 1 (IGF1) is an important growth promoting peptide which has anabolic effects on in vitro cartilage metabolism. The fact that serum levels tend to decrease in elderly subjects while osteoarthritis (OA) increases in prevalence suggests that suboptimal levels may play a part in the development of OA. This study therefore considers the hypothesis that IGF1 levels are low in subjects with OA of the knee. METHODS: Serum IGF1 levels in a community derived sample with symptomatic knee OA were compared with those in normal controls matched by age and gender. Overall radiographic score, osteophyte score, sclerosis score, and joint space narrowing score were correlated with IFG1 levels. RESULTS: One hundred and seventy-seven elderly subjects (83 with knee pain, 94 without knee pain) participated, allowing the identification of 78 case-control pairs matched by age and gender (mean 71.8 v 71.9 years, SD 7.6 for the two groups). No difference was found in serum IGF1 levels between the cases and controls (mean(SD) 15.9(4.7) nmol/l, for cases, 16.4(5.4) for controls). Significant negative correlations were found between IGF1 levels and age, total radiographic score, osteophyte score, and sclerosis score. In a multiple regression model, however, only age remained significant. CONCLUSIONS: This study provides no evidence that serum IGF1 levels are low in OA. Apparent correlations with radiographic features of OA may be due to the confounding effects of age. PMID- 8484679 TI - Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. AB - In rheumatoid synovium interleukin 6 (IL-6) is the most abundantly expressed cytokine. Increased serum levels have been previously reported in patients with rheumatoid arthritis (RA). In this study serum IL-6 levels were measured in a well defined cohort using a bioassay (B9 cells) and levels were correlated with conventional clinical and laboratory indices of disease activity. Levels were significantly higher in serum from patients with RA (median 55 IU/ml; interquartile range 28-139) compared with serum from disease (median 7 IU/ml; 1 23) and normal controls (median 10 IU/ml; 7-12). No difference was observed between men and women. Levels did not correlate with disease duration. Significant associations were observed between IL-6 and C reactive protein and between the Ritchie articular index and duration of morning stiffness. No other correlations were observed. The value of these findings in the monitoring of RA and as an indicator of response to second line treatment needs to be established. PMID- 8484680 TI - New application of myocardial antimyosin scintigraphy: diagnosis of myocardial disease in polymyositis. AB - Heart disease is a rare but important complication of polymyositis. Diagnosis of myocardial disease is usually based on non-specific clinical, electrocardiographic, and echocardiographic data. This paper reports a case of polymyositis with myocardial disease diagnosed by myocardial imaging with radiolabelled antibody to myosin, a specific marker of the necrotic myocardial fibre. PMID- 8484681 TI - Rapidly progressive sacroiliitis in a patient with lymphocytic lymphoma. AB - Rheumatological manifestations may develop as paraneoplastic syndromes in patients with malignancy. Sacroiliitis and spondyloarthropathy have not, however, been previously associated with cancer. The case is described of a patient with a stage IV diffuse well differentiated lymphocytic lymphoma who developed concomitant sacroiliitis and enthesopathies with rapid progression following the diagnosis of malignancy. PMID- 8484682 TI - Why are non-steroidal anti-inflammatory drugs so variable in their efficacy? A description of ion trapping. PMID- 8484683 TI - Dorsal vertebral fractures with 'normal' bone mineral density. PMID- 8484684 TI - RA sex ratios, HLA-DR, and testosterone. PMID- 8484685 TI - von Willebrand factor, exercise, and ischemia/reperfusion injury. PMID- 8484686 TI - Elusive 'alpha-delta' sleep in fibromyalgia and osteoarthritis. PMID- 8484687 TI - Buerger's disease and antiphospholipid antibodies in pregnancy. PMID- 8484688 TI - Fibromyalgia in the workplace: a 'management' problem. PMID- 8484689 TI - Prevalence of rheumatoid arthritis and rheumatoid factor in women: evidence for a secular decline. AB - OBJECTIVE: To determine the current prevalence of rheumatoid arthritis (RA) and rheumatoid factor positivity in the United Kingdom middle aged female population and to compare this with previous estimates to assess whether the disease is becoming less prevalent. METHODS: A cross sectional prevalence study was undertaken. All women aged 45-64 from the age and sex register of a large 11,000 general practitioner group practice in Chingford, East London were contacted and responders examined clinically and radiographically for the presence of RA by a single observer. Blood was also taken for rheumatoid factor testing (sheep cell agglutination test (SCAT), latex, and IgG). The prevalence in non-attenders was assessed from general practitioner and local hospital records. A diagnosis of definite or classical RA according to 1958 American Rheumatism Association criteria was used, and seropositivity was defined by a SCAT rheumatoid factor of 1/32 or more. RESULTS: From the 1003 women examined (response rate of 78.8%), 12 women had definite RA (1.2%, 95% confidence interval 0.6 to 1.8). Of these, 7/12 had definite erosive changes on radiography and 3/12 had a positive SCAT (> 1/32). Three cases of RA were also found in the 284 non-responders (prevalence 1.1%) by case-finding techniques. The rate of SCAT positivity in the whole study group was 0.5%. The rates of RA and SCAT positivity currently found in this group were less than those obtained in previous surveys. In the only previous large scale United Kingdom survey, performed in the north of England between 1958 and 1960, 406 women aged 45-64 were examined and 10 cases of definite RA were found, a prevalence of 2.5%. In the patients with RA 68% had erosions and 63% positive SCAT. The population SCAT positive rate in this and other surveys sampled between 1954 and 1961 was in the range of 4-5%, since when there has been a progressive decline according to a number of other studies. CONCLUSIONS: The prevalence of RA and rheumatoid factor in middle aged women is lower than previously believed and supports a variety of other data which indicate that RA is declining in incidence and severity. PMID- 8484690 TI - Determinants of disability in osteoarthritis of the knee. AB - OBJECTIVES: To evaluate the influences of radiographic severity, quadriceps strength, knee pain, age, and gender on functional ability in patients with osteoarthritis of the knee. METHODS: Equal numbers of knee pain positive and negative respondents to a survey of registrants aged more than 55 years at a general practice were invited to attend for knee radiographs and quadriceps femoris isometric strength estimations. Disability was measured using the Stanford Health Assessment Questionnaire. RESULTS: Complete data were available on 70 men (mean age 72.7 years) and 89 women (mean age 68.1 years); 44% reported knee pain, 48% had radiographic features of osteoarthritis, and 32% reported some degree of disability. Significant correlations were observed between disability and radiographic score, quadriceps strength, and knee pain. Logistic regression analysis, however, showed significant independent contributions from quadriceps strength (odds ratio 0.84 kgF), knee pain (odds ratio 1.67), and age (odds ratio 1.06 per year) only; the radiographic score had no influence on the model. These results were not influenced by confining the analysis to the group with radiographic features of osteoarthritis. CONCLUSIONS: Quadriceps strength, knee pain, and age are more important determinants of functional impairment in elderly subjects than the severity of knee osteoarthritis as assessed radiographically. Strategies designed to optimise muscle strength may have the potential to reduce a vast burden of disability, dependency, and cost. PMID- 8484691 TI - Radiographic progression of hospital referred osteoarthritis of the hip. AB - Various factors have been considered important in the rate of progression of osteoarthritis of the hip, though few data are available from large longitudinal studies. One hundred and thirty six patients referred to hospital (85 women, 51 men; mean age 65 years, range 29-86 years) with osteoarthritis of the hip (192 affected hips) were followed up for a median of 27 (range 3-72) months. One hundred and six patients (144 affected hips) were reviewed for a minimum of one year (median 28, range 12-72 months). Fifty three per cent of all osteoarthritic hips required an operation at a median of 14 (range 3-48) months from entry. All radiographs before and after entry were examined (median four films for each patient over a median of three years, range 0.5-19 years). Hips showing rapid radiographic progression on prospective films more often had superior migration, or an atrophic bone response; those with no progression more often had an indeterminate, medial, or axial migration pattern, protrusio or mild osteoarthritis at presentation. A higher occurrence of rapid progression was seen in women, in those of older age at symptom onset, and in hips with a higher Kellgren grade at entry; men more often showed no progression. Age at presentation, body mass index, symptom duration, or presence of chondrocalcinosis, hand osteoarthritis/nodes, or Forestier's disease did not influence progression. This study supports the contention that, at the time of hospital referral, certain patient characteristics and radiographic features at the hip may help to identify those at high risk of rapidly progressive hip osteoarthritis. PMID- 8484692 TI - Expression of systemic lupus erythematosus in various ethnic Jewish Israeli groups. AB - OBJECTIVES: To assess the expression of systemic lupus erythematosus (SLE) in Jewish Israeli patients according to ethnic origin. METHODS: Eighty four patients with SLE were divided into groups according to origin and compared for history, physical examination, and laboratory variables. RESULTS: Patients of Sephardic origin had more serious disease manifestations than Ashkenazi patients in 60 of the 76 variables examined. They had significantly worse muscle pain, alopecia, and cutaneous vasculitis, higher antibodies to DNA and erythrocyte sedimentation rate, and significantly lower complement and leucocytes. Sephardic patients were divided into subgroups according to country: Mediterranean area, Iran-Iraq-India, and Yemen. All three subgroups had more serious disease manifestations than the Ashkenazi group, and the Yemenite patients had the most serious manifestations among the Sephardic subgroups. The Sephardic patients had a significantly lower education level, but only origin, and not education level or age, was significantly related to disease manifestations on multivariate analysis. CONCLUSION: More serious manifestations of SLE are found among Jewish patients of Sephardic origin, but these are not related to level of education or age. PMID- 8484693 TI - Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity. AB - OBJECTIVES: The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process of scleroderma. METHODS: The two colour expression of surface molecules by circulating T cells was analysed with a panel of monoclonal antibodies and flow cytometry in 17 patients with scleroderma, 10 patients with systemic lupus erythematosus, and five patients with rheumatoid arthritis, and the results compared with those for 10 normal controls. The two colour T CD4+ phenotype was further compared between patients with active and quiescent disease in these patients with scleroderma. The coexpression of surface molecules by CD4+ T cells was also analysed by three colour flow cytometry in eight patients with scleroderma. RESULTS: Patients with scleroderma showed increased CD4+CD26+ and CD4+CD25+ percentages and absolute numbers and decreased CD8+CD29+ percentages compared with controls. Moreover, a significant correlation between the higher CD4+CD26+ T cell percentage and absolute cell numbers with disease activity was observed. Most of the CD4+ peripheral blood T cells from patients with scleroderma showed the CD26+CD45RA- phenotype by three colour flow cytometry analysis. CONCLUSIONS: The distinctive pattern of early helper memory T cell activation in these patients with rapidly evolving scleroderma supports the role of a T cell mediated mechanism in the progression of scleroderma. PMID- 8484694 TI - Detection of Luse bodies, spiralled collagen, dysplastic collagen, and intracellular collagen in rheumatoid connective tissues: an electron microscopic study. AB - BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease leading to alterations of the extracellular matrix in tendons, ligaments, and cartilage. The structural changes of the collagenous systems in rheumatoid connective tissues are largely unknown, however. METHODS: Thirty four samples of menisci, 36 cruciate ligaments, and four tendons were taken during joint surgery in patients with rheumatoid arthritis. Eighteen menisci, 35 ligaments, and 30 tendons obtained at necropsy served as a control group. The extracellular matrix in the two groups was analysed by the combined use of transmission and scanning electron microscopy, immunohistochemistry with monoclonal antibodies recognising collagen types IV and VI, and ultramorphometry. RESULTS: Normal tendons and ligaments predominantly showed a unidirectional fibril arrangement. Whereas type IV collagen showed a positive staining pattern along all basement membranes, type VI collagen formed fine, filaments aligned in parallel. In patients with rheumatoid arthritis a significant reduction of the mean diameter of the collagen fibrils was found owing to the presence of thin collagenous fibrils 20-60 nm in diameter. Most of these fibrils showed considerable changes in their arrangement with irregular courses (so-called interfibrillar dysplastic collagen). Up to 410 nm thick frayed fibrils with irregular outlines (spiralled collagen) and intracellular collagen forms were found in rheumatoid tissues. In addition, atypical thick collagenous structures with 41 nm periodicity (Luse bodies) were detected in the matrix. The upregulation of type IV collagen in rheumatoid arthritis was associated with an increase in the vascular density. The expression of type VI collagen was upregulated in fibrotic zones. CONCLUSIONS: The dramatic ultrastructural collagen changes lead to a structural and functional insufficiency of the extracellular matrix in rheumatoid connective tissues. The results suggest that collagen alterations may contribute to the development of tendon and ligament ruptures in rheumatoid arthritis. PMID- 8484695 TI - Protective effect of androgens against inflammation induced cartilage degradation in male rodents. AB - OBJECTIVES: Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS: An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS: Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS: Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability. PMID- 8484696 TI - Effect of tenidap on cartilage integrity in vitro. AB - OBJECTIVES: The maintenance of articular cartilage integrity during long term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is of clinical importance. These experiments were set up to test the action of tenidap, naproxen, and diclofenac on bovine and porcine cartilage, matrix synthesis, and catabolism. METHODS: Short term organ culture techniques were used to determine the effect of interleukin 1 (IL-1) on synthesis and degradation, and the action of tenidap and the other drugs on these parameters. The retention of glycosaminoglycans (GAGs) and the synthesis of GAGs by incorporation of sulphur 35 labelled sulphate was used to determine the chondrocyte metabolic activity. RESULTS: The action of human recombinant interleukin 1 alpha (hrIL-1 alpha) in increasing catabolic activity and inhibiting synthetic activity of the animal cartilages was confirmed. Tenidap was shown to give substantial and significant protection against the catabolic effects of hrIL-1 alpha and, to a lesser degree, against the inhibition of matrix synthesis by the cytokine. Neither diclofenac nor naproxen in doses expected to occur in the synovial fluid showed this action. Tenidap also inhibited the GAG loss from cocultures and, to a moderate degree, reversed the inhibition of synthesis by synovial tissue. Tenidap also stimulated cartilage repair activity during recovery from IL-1 treatment. The optimum concentration of the action against IL-1 was between 5 and 10 micrograms/ml. Above this concentration tenidap itself showed some inhibitory action on GAG synthesis. CONCLUSIONS: Bearing in mind the problems in extrapolating from in vitro work on animal cartilages to humans, it seems possible that tenidap may be useful in decreasing the deleterious action of cytokines such as IL-1 on cartilage integrity during arthritic disease and in stimulating chondrocyte repair processes. PMID- 8484697 TI - Gold induced nephropathy in rheumatoid arthritis and HLA class II genes. AB - OBJECTIVES: To elucidate the role of HLA-DRB, -DQA, and -DQB genes in patients with rheumatoid arthritis (RA) who developed gold induced nephropathy. METHODS: Southern blot analysis of HLA-DRB, -DQA, and -DQB genes was performed on DNA from 27 patients with RA with gold induced nephropathy, 37 patients with RA who were treated with gold but did not develop nephropathy, and 122 ethnically matched normal subjects. RESULTS: The 4.7 kb DQA1/Taq I band associated with DQA1*0501 and DR3 and DR5 was found in 16 (59%) patients with gold induced nephropathy compared with five (14%) patients without gold induced nephropathy. CONCLUSION: It is concluded that HLA-DQA region genes may be an important susceptibility factor for the development of gold induced nephropathy in patients with RA. PMID- 8484698 TI - Adjuvant oestrogen treatment increases bone mineral density in postmenopausal women with rheumatoid arthritis. AB - OBJECTIVES: The beneficial effect of oestrogens on bone mineral density in women with osteoporosis is well known. Patients with rheumatoid arthritis (RA) are at risk for osteoporosis. A study was therefore set up to investigate the effects of adjuvant oestrogen treatment on bone metabolism and bone mineral density in postmenopausal women with RA. METHODS: Forty postmenopausal women with active RA were admitted to a placebo controlled, double blind study investigating the beneficial effect of adjuvant oestradiols or placebo on bone metabolism and bone mineral density. Thirty three patients completed 52 weeks of treatment. RESULTS: At the start both treatment groups were comparable for all parameters. In the oestrogen group serum concentrations of osteocalcin decreased and concentrations of sex hormone binding globulin increased during the study. Bone mineral density measured by dual energy x ray absorptiometry increased significantly in the lumbar vertebral spine and femoral neck in the oestrogen group compared with the placebo group. CONCLUSIONS: This study shows that the use of adjuvant oestrogens in post-menopausal women with active RA increases bone mineral density. PMID- 8484699 TI - Ossification of the ligamentum teres as a possible mechanism of lateral subluxation in coxopathy associated with ankylosing spinal hyperostosis. AB - The cases are reported of two patients with coxopathy associated with ankylosing spinal hyperostosis who showed ossification of the ligamentum teres. It is suggested that considerable ossification at the medial acetabular floor including the ligamentum teres can explain the mechanism of development of coxopathy with lateral subluxation of the femoral head which is often seen in patients with ankylosing spinal hyperostosis. PMID- 8484700 TI - Rapid development of a tophus following ipsilateral hemiparesis. AB - An 85 year old man with a longstanding history of non-tophaceous gout developed a single large tophus, unassociated with inflammation, on his paretic leg over a six week period following an acute hemiplegia. The rapidity of tophus formation, its localisation to the paretic limb, and the apparent blunting of the acute inflammatory response represent a previously unreported interaction between gout and neurological deficit. PMID- 8484701 TI - Epidemiological approaches to the immunogenetics of autoimmune rheumatic disease. PMID- 8484702 TI - Spontaneous splenic rupture in Wegener's vasculitis. PMID- 8484703 TI - Menstrual arthritis. PMID- 8484704 TI - Folate supplementation and methotrexate. PMID- 8484705 TI - Bone mineral density and osteoarthritis. PMID- 8484706 TI - The antiquity of rheumatoid arthritis. PMID- 8484707 TI - Anaerobic transformation of 2,4,6-trinitrotoluene (TNT). AB - A sulfate-reducing bacterium using trinitrotoluene (TNT) as the sole nitrogen source was isolated with pyruvate and sulfate as the energy sources. The organism was able to reduce TNT to triaminotoluene (TAT) in growing cultures and cell suspensions and to further transform TAT to still unknown products. Pyruvate, H2, or carbon monoxide served as the electron donors for the reduction of TNT. The limiting step in TNT conversion to TAT was the reduction of 2,4-diamino-6 nitrotoluene (2,4-DANT) to triaminotoluene. The reduction proceeded via 2,4 diamino-6-hydroxylaminotoluene (DAHAT) as an intermediate. The intermediary formation of DAHAT was only observed in the presence of carbon monoxide or hydroxylamine, respectively. The reduction of DAHAT to triaminotoluene was inhibited by both CO and NH2OH. The inhibitors as well as DANT and DAHAT significantly inhibited sulfide formation from sulfite. The data were taken as evidence for the involvement of dissimilatory sulfite reductase in the reduction of DANT and/or DAHAT to triaminotoluene. Hydrogenase purified from Clostridium pasteurianum and carbon monoxide dehydrogenase partially purified from Clostridium thermoaceticum also catalyzed the reduction of DANT in the presence of methyl viologen or ferredoxin, however, as the main reduction product DAHAT rather than triaminotoluene was formed. The findings could explain the function of CO as an electron donor for the DANT reduction (to DAHAT) and the concomitant inhibitory effect of CO on triaminotoluene formation (from DAHAT) by the inhibition of sulfite reductase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484708 TI - Morphological, physiological and enzymatic characteristics of cephalosporin acylase-producing Arthrobacter strain 45-8A. AB - A bacterial strain producing cephalosporin acylases was isolated from soil. The morphological and physiological properties of this strain suggest that it belongs to the genus Arthrobacter, and the isolate was therefore designated Arthrobacter strain 45-8A. Substrate specificity of the enzyme was examined. The enzyme can convert both cephalosporin acid to 7-aminocephalosporanic acid. An interesting feature of the acylases is their temperature-dependent regulation. Activity of acylases was detected in strain 45-8A grown at temperature below 30 degrees C, but was not observed at higher temperature. Arthrobacter strain 45-8A did not exhibit beta-lactamase activity, even though its resistance to cephalosporin C was very strong (> 2000 micrograms/ml). This is quite beneficial for its application in the manufacture of 7-aminocephalosporanic acid. PMID- 8484710 TI - Keep Medicare healthy. PMID- 8484709 TI - Pentose utilization and transport by the ruminal bacterium Prevotella ruminicola. AB - Plant cell wall polysaccharides are primarily composed of hexose or hexose derivatives, but a significant fraction is hemicellulose which contains pentose sugars. Prevotella ruminicola B14, a predominant ruminal bacterium, simultaneously metabolized pentoses and glucose or maltose, but the organism preferentially fermented pentoses over cellobiose and preferred xylose to sucrose. Xylose and arabinose transport at either low (2 microM) or high (1 mM) substrate concentrations were observed only in the presence of sodium and if oxygen was excluded during the harvest and assay procedures. An artificial electrical potential (delta psi) or chemical gradient of sodium (delta pNa) drove transport in anaerobically prepared membrane vesicles. Because (i) transport was electrogenic, (ii) a delta pNa drove uptake, and (iii) the number of sodium binding sites was approximately 1, it appeared that P. ruminicola possessed pentose/sodium support mechanisms for the transport of arabinose and xylose at low substrate concentrations. Pentose uptake exhibited a low affinity for xylose or arabinose (> 300 microM), and transport of xylose exhibited bi-phasic kinetics which suggested that a second sodium-dependent xylose transport system was present. Little study has been made on solute transport by Prevotella (Bacteroides) species and this work represents the first use of isolated membrane vesicles from these organisms. PMID- 8484711 TI - Women's health initiatives: promoting women's health; early detection of breast cancer--a national program. PMID- 8484712 TI - Australian Nursing Federation health policy. PMID- 8484713 TI - Toward a social theory of psychiatric phenomena. AB - This essay relies on a positivistic/scientific perspective to define psychiatric phenomena. However, it draws a distinction between a biomedical versus a social science approach. The aim is to review some of the theoretical and empirical considerations that pertain to psychiatric phenomena that need to be addressed in order to develop a social theory about them. The object of the theory is to explain how psychiatric phenomena are labeled, interpreted, and handled across societies that differ in terms of social structure and culture. Some of the kinds of variables and questions that would allow for cross-cultural analyses are identified. In addition, two topics that a social theory could address--that of the medicalization and stigmatization of psychiatric phenomena--are introduced. These topics are elaborated by developing propositions that substantively illustrate the questions/hypotheses of a social theory of psychiatric phenomena. The essay illustrates that a social theory constitutes a complex enterprise that requires dealing with philosophical, methodological and empirical issues. PMID- 8484715 TI - Activation of oxidized cysteine proteinases by thioredoxin-mediated reduction in vitro. AB - Activity of the cysteine adducts of the cysteine proteinases papain and thaumatopain can be recovered by treatment with thioredoxin, thioredoxin reductase and NADPH. Recovery of proteinase activity did not occur if any of the components of the thioredoxin system were omitted, or if thioredoxin or thioredoxin reductase were heat-inactivated. Such an enzyme-mediated process may be of significance in the recovery of cysteine proteinases inactivated by oxidative attack. PMID- 8484714 TI - Protein kinase C isoenzymes: divergence in signal transduction? PMID- 8484716 TI - A novel N-terminal motif for palmitoylation of G-protein alpha subunits. AB - We have examined the post-translational processing of G alpha subunits expressed endogenously in rat PC12 and NG108-15 rat/mouse hybrid cells, and after transfection of cDNA expression constructs into COS cells. Thioester-linked palmitoylation of alpha o, alpha s, alpha q/alpha 11 and alpha 12 has been detected by metabolic labelling with [3H]palmitate and immunoprecipitation. Palmitoylation of alpha o occurs post-translationally in cells treated with protein-synthesis inhibitors, suggesting possible dynamic acylation. Palmitoylation of the C-terminal CAAX motif has been excluded. Site-directed mutagenesis of alpha o has been used to implicate the site of modification as a cysteine residue next to the N-terminal myristoylated glycine, in a novel protein lipid modification motif Met-Gly-Cys. The non-palmitoylated alpha o mutant is still myristoylated but shows reduced membrane binding, suggesting that reversible palmitoylation may regulate G alpha localization and function. PMID- 8484717 TI - Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver. AB - An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Haussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane. PMID- 8484718 TI - Versican gene expression in human articular cartilage and comparison of mRNA splicing variation with aggrecan. AB - The chondrocytes in human articular cartilage from subjects of all ages express mRNAs for both of the aggregating proteoglycans aggrecan and versican, although the level of expression of versican mRNA is much lower than that of aggrecan mRNA. Aggrecan shows alternative splicing of the epidermal growth factor (EGF) like domain within its C-terminal globular region, but there is no evidence for a major difference in situ in the relative expression of this domain with age. At all ages studied from birth to the mature adult, a greater proportion of transcripts lacked the EGF domain. The relative proportions of the two transcripts did not change upon culture and passage of isolated chondrocytes. In contrast, the neighbouring complement regulatory protein (CRP)-like domain was predominantly expressed irrespective of age, but cell culture did result in variation of the splicing of this domain. Versican possesses two EGF-like domains and one CRP-like domain, but at all ages the three domains were predominantly present in all transcripts. This situation persisted upon culture and passage of the chondrocytes. Thus, unlike aggrecan, the versican expressed by human articular cartilage does not appear to undergo alternative splicing of its C terminal globular region, either in cartilage in situ or in chondrocytes in culture. PMID- 8484719 TI - G-protein from Medicago sativa: functional association to photoreceptors. AB - G-protein subunits were characterized from Medicago sativa (alfalfa) seedlings. Crude membranes and GTP-Sepharose-purified fractions were electrophoresed on SDS/polyacrylamide gels and analysed by Western blotting with 9193 (anti-alpha common) and AS/7 (anti-alpha t, anti-alpha i1 and anti-alpha i2) polyclonal antibodies. These procedures led to the identification of a specific polypeptide band of about 43 kDa. Another polypeptide reacting with the SW/1 (anti-beta) antibody, of about 37 kDa, was also detected. The 43 kDa polypeptide bound specifically [alpha-32P]GTP by a photoaffinity reaction and was ADP-ribosylated by activated cholera toxin, but not by pertussis toxin. Irradiation of etiolated Medicago sativa protoplast preparations at 660 nm for 1 min produced a maximal increase in the guanosine 5'-[gamma-thio]triphosphate (GTP[35S])-binding rate. After this period of irradiation, the binding rate tended to decrease. The effect of a red-light (660 nm) pulse on the binding rate was reversed when it was immediately followed by a period of far-red (> 730 nm) illumination. These results may suggest that activation of GTP[S]-binding rate was a consequence of conversion of phytochrome Pr into the Ptr form. PMID- 8484720 TI - Binding of the calcium antagonist flunarizine to phosphatidylcholine bilayers: charge effects and thermodynamics. AB - We have examined the partitioning/transfer of the Ca2+ antagonist flunarizine from the aqueous phase into phospholipid bilayers. We show that the binding of the cationic amphiphilic drug flunarizine to phospholipid bilayers displays traditional linear concentration-dependent characteristics once unmasked of electrostatic effects. The coefficient for the binding/partitioning of flunarizine to phosphatidylcholine was found to be 28700 M-1, supporting the notion that this drug may be particularly membrane-active. The thermodynamics of the partitioning/transfer process have also been studied using high-sensitivity titration calorimetry. Binding was found to be predominantly enthalpy-driven with only a small entropic contribution; delta H = -22.1 kJ.mol-1 (-5.3 kcal.mol-1) at 27 degrees C. This is in conflict with established ideas of entropy-driven partitioning of drugs into phospholipid membranes as a result of the 'hydrophobic effect'. The strong enthalpic nature of binding is interpreted as being indicative of strong lipophilic interactions between the drug and the phospholipid phase. PMID- 8484721 TI - Interaction of caldesmon with phospholipids. AB - The interaction of caldesmon with liposomes composed of various phospholipids has been examined by tryptophan fluorescence spectroscopy. The results indicate that caldesmon makes its strongest complex with phosphatidylserine (PS) vesicles (Kass. = 1.45 x 10(5) M-1). Both electrostatic and hydrophobic interactions contribute to the stability of this complex. The site for strong binding of PS seems to be located in the N-terminal part of the 34 kDa C-terminal fragment of caldesmon. Binding of PS at this site results in displacement of calmodulin from its complex with caldesmon. PMID- 8484722 TI - ADP-ribosylation of Drosophila indirect-flight-muscle actin and arthrin by Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin. AB - Purified Drosophila indirect-flight-muscle actin and arthrin, an actin-ubiquitin conjugate, were ADP-ribosylated by Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin. Phalloidin treatment inhibited the ADP-ribosylation of Drosophila actin and arthrin. Like actin, the ADP-ribose-arthrin linkage was sensitive towards hydroxylamine treatment, indicating arginine as the amino acid acceptor. Actin translated in vitro from the indirect-flight-muscle-specific gene Act88F was ADP-ribosylated by C. botulinum C2 toxin and C. perfringens iota toxin. Actin from the R177Q mutant of Act88F translated in vivo was not ADP ribosylated confirming Arg-177 as the ADP-ribose acceptor. Mutant L176M actin was modified by both toxins, indicating that amino acid 176 of actin does not define the substrate specificity of C. botulinum C2 toxin. Whereas the gene products of various C-terminal mutants of Act88F translated in vitro (E334K, V339I, E364K, G368E, R372H) were substrates for ADP-ribosylation by C. botulinum C2 toxin and by C. perfringens iota toxin, neither toxin modified the N-terminal O-12 deletion mutant. PMID- 8484723 TI - The lithocholic acid 6 beta-hydroxylase cytochrome P-450, CYP 3A10, is an active catalyst of steroid-hormone 6 beta-hydroxylation. AB - CYP 3A10 is a hamster liver cytochrome P-450 (P450) that encodes lithocholic acid 6 beta-hydroxylase, an enzyme that plays an important role in the detoxification of the cholestatic secondary bile acid lithocholate. Western-blot analysis revealed that the expression of CYP 3A10 protein is male-specific in hamster liver microsomes, a finding that is consistent with earlier analysis of CYP 3A10 mRNA. Since it has not been established whether the specificities of bile acid hydroxylase P450s, such as CYP 3A10, are restricted to their anionic bile acid substrates, we investigated the role of CYP 3A10 in the metabolism of a series of neutral steroid hormones using cDNA directed-expression in COS cells. The steroid hormones examined, testosterone, androstenedione and progesterone, were each metabolized by the expressed CYP 3A10, with 6 beta-hydroxylation corresponding to a major activity in all three instances. CYP 3A10-dependent steroid hydroxylation was increased substantially when the microsomes were prepared from COS cells co transfected with NADPH:P450 reductase cDNA. In this case, the expressed P450 actively catalysed the 6 beta-hydroxylation of testosterone (288 +/- 23 pmol of product formed/min per mg of COS-cell microsomal protein), androstenedione (107 +/- 19 pmol/min per mg) and progesterone (150 +/- 7 pmol/min per mg). Other major CYP 3A10-mediated steroid hydroxylase activities included androstenedione 16 alpha-hydroxylation, progesterone 16 alpha- and 21-hydroxylation, and the formation of several unidentified products. CYP 3A10 exhibited similar Vmax. values for the 6 beta-hydroxylation of androstenedione and lithocholic acid (132 and 164 pmol/min per mg respectively), but metabolized the bile acid with a 3 fold lower Km (25 microM, as against 75 microM for androstenedione). Together, these studies establish that the substrate specificity of the bile acid hydroxylase CYP 3A10 is not restricted to bile acids, and further suggest that CYP 3A10 can play a physiologically important role in the metabolism of two classes of endogenous P450 substrates:steroid hormones and bile acids. PMID- 8484724 TI - Regulation of the ovine intestinal Na+/glucose co-transporter (SGLT1) is dissociated from mRNA abundance. AB - We have investigated the mechanisms of regulation of the Na+/glucose co transporter (SGLT1) in a ruminant animal, which is an exceptional model system for studying intestinal glucose transport. Pre-ruminant lambs absorb glucose, produced by hydrolysis of the milk sugar lactose, in the intestine via apical SGLT1 and basolateral facilitative glucose transporters (GLUT2). Weaning coincides with the development of the rumen, and consequently the amount of hexoses reaching the small intestine of the ruminant sheep is undetectable. During development, SGLT1 activity and abundance in intestinal brush-border membranes decreased by over 200-fold, and either maintaining lambs on a milk replacer diet or infusing sheep intestine with D-glucose restored co-transporter activity and expression. We have measured ovine intestinal SGLT1 mRNA levels during development, with changes in diet and after direct infusion of D-glucose or methyl alpha-D-glucopyranoside into the intestinal lumen, in order to determine the level of regulation. During development, mRNA levels decreased only 4-fold. Lambs maintained on a milk replacer diet showed no change in mRNA levels relative to age-matched controls. Finally, upon infusion of the intestine of the ruminant sheep with sugars, D-glucose infusion increased SGLT1 mRNA, but only by 2-fold, compared with a 60-90-fold increase in co-transporter number and activity. Since the change in Na(+)-dependent glucose transport activity is correlated with SGLT1 protein abundance, and since changes in mRNA levels do not account for the dramatic changes in protein abundance, we conclude that the principal level of SGLT1 regulation by luminal sugar is translational or post translational. PMID- 8484725 TI - Intracellular Ca2+ pools in Jurkat T-lymphocytes. AB - Jurkat T-lymphocytes comprise at least four intracellular Ca2+ pools. Pool I was agonist-sensitive and contained 23 +/- 8% (n = 18) of the total Ca(2+)-storage capacity, as shown in intact cells in the presence of EGTA. The time courses of the agonist-induced formation of Ins(1,4,5)P3 and of the Ca2+ release from pool I were nearly superimposable, indicating that the agonist-sensitive pool I is emptied by Ins(1,4,5)P3. Likewise, in permeabilized cells, the size of the Ins(1,4,5)P3-sensitive Ca2+ pool I was 27 +/- 11% (n = 14). Pool II contained 26 +/- 5% (n = 9) of intracellularly stored Ca2+ and was liberated by thapsigargin, an inhibitor of the endoplasmic-reticulum (ER) Ca(2+)-ATPase. Addition of thapsigargin before addition of agonist abolished the agonist-induced Ca2+ release in both intact and permeabilized cells, indicating that pool I is a subcompartment of the ER Ca2+ pool. The content of this ER Ca2+ pool (pools I and II) amounted to 51 +/- 15% (n = 9) in intact cells and 49 +/- 16% (n = 16) in permeabilized cells. Caffeine released Ca2+ even when the ER pool (pools I and II) was emptied by previous addition of thapsigargin, indicating the presence of a third pool independent of pools I and II. Pool III contained 23 +/- 6% (n = 8) in intact cells, but 41 +/- 8% (n = 5) in permeabilized cells. The remaining intracellularly stored Ca2+ was released by addition of the Ca2+ ionophore ionomycin. This fourth pool contained 27 +/- 8% (n = 9) in intact cells, but less than 10% in permeabilized cells. The size of pool III was increased when pools I and II were emptied before addition of caffeine, whereas the size of pool IV was decreased under such conditions. In conclusion, this first comprehensive description of intracellular Ca2+ pools in Jurkat T-lymphocytes demonstrates the presence of four different Ca2+ pools, provides estimates of their sizes and describes relationships between each other. Release of Ca2+ from pool I [Ins(1,4,5)P3-sensitive] has previously been shown to play a major role in T-cell activation, whereas the physiological role of pools II-IV remains to be established. PMID- 8484726 TI - Effects of hyperbilirubinaemia on glutathione S-transferase isoenzymes in cerebellar cortex of the Gunn rat. AB - The glutathione S-transferases (GSTs) are a family of isoenzymes involved in the detoxication of a variety of electrophilic xenobiotics. The present investigation demonstrates that GST activity and the concentration of cytosolic GSTs in cerebellar cortex of Gunn rats were increased in hyperbilirubinaemic animals compared with non-jaundiced controls. Age-dependent and region-specific increases in GST isoenzymes were seen in three regions of the cerebellar cortex of jaundiced Gunn rats, whereas GST concentrations were not altered in the brainstem, thalamus/hypothalamus, cortex or liver. Cytosolic GST activity was increased 1.3-fold in the flocculus and lateral hemispheres of 20-day-old and 1.7 fold in the flocculus, lateral hemispheres and vermis of 60-day-old jaundiced (jj; homozygous) Gunn rats compared with non-jaundiced (Jj; heterozygous) Gunn rats. H.p.l.c. was used to determine the GST subunit protein concentrations in cytosolic fractions isolated from liver and brain regions of jaundiced and non jaundiced animals. In all regions of the cerebellum from 20-day-old animals, the levels of Alpha-class GST subunits 2 (Yc1; 3.0-fold) and 8 (Yk; 2.0-fold) were increased in jaundiced rats. In 60-day-old animals, the concentrations of Alpha class GST subunits 2 (Yc1; 5.0-fold) and 8 (Yk; 3.0-fold), Mu-class subunit 11 (Yo; 2.5-fold) and Pi-class subunit 7 (Yp; 2.0-fold) were increased in all regions of cerebellar cortex of jaundiced animals. In cerebellum of 10-, 20- and 60-day-old non-jaundiced and jaundiced Gunn rats, the flocculus had the highest concentration of Mu-class GST subunit 4 (Yb2) and vermis the lowest; hyperbilirubinaemia increased the concentration of subunit 4 (Yb2; 3- to 5-fold) in the flocculus and lateral hemispheres, but not the vermis, of 20- and 60-day old rats. Intraperitoneal injection of sulphadimethoxine, a long-acting sulphonamide which displaces bilirubin from its albumin-binding sites and increases the bilirubin levels in tissues, further increased the already elevated concentrations of GST subunits in the lateral regions of cerebellar cortex of hyperbilirubinaemic rats. For example, the concentration of subunit 4 (Yb2) was increased 2.2-fold (compared with non-jaundiced controls) in Gunn rats injected with saline and 7.4-fold in rats injected with 100 mg of sulphadimethoxine/kg body weight. In contrast, GSTs in the vermis of jaundiced animals were not affected by sulphadimethoxine injection. Sulphadimethoxine had no effect on GST concentrations in lateral regions and vermis of heterozygous (Jj) Gunn rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8484727 TI - Selective labelling and inactivation of creatine kinase isoenzymes by the thyroid hormone derivative N-bromoacetyl-3,3',5-tri-iodo-L-thyronine. AB - Besides their well-known regulation of transcription by binding to nuclear receptors, thyroid hormones have been suggested to have direct effects on mitochondria. In a previous study, incubation of rat heart mitochondria with 125I labelled N-bromoacetyl-3,3',5-tri-iodo-L-thyronine (BrAcT3), a thyroid hormone derivative with an alkylating side chain, resulted in the selective labelling of a protein doublet around M(r) 45,000 on SDS/polyacrylamide gels [Rasmussen, Kohrle, Rokos and Hesch (1989) FEBS Lett. 255, 385-390]. Now, this protein doublet has been identified as mitochondrial creatine kinase (Mi-CK). Immunoblotting experiments with the cytoplasmic and mitochondrial fractions of rat heart, brain and liver, as well as inactivation studies with the purified chicken CK isoenzymes have further demonstrated that all four CK isoenzymes (Mia , Mib-, M- and B-CK) are indeed selectively labelled by BrAcT3. However, in contrast with their bromoalkyl derivatives, thyroid hormones themselves did not compete for CK labelling, suggesting that not the thyroid hormone moiety but rather the bromoacetyl-driven alkylation of the highly reactive 'essential' thiol group of CK accounts for this selective labelling. Therefore the assumption that CK isoenzymes are thyroid-hormone-binding proteins has to be dismissed. Instead, bromoacetyl-based reagents may allow a very specific covalent modification and inactivation of CK isoenzymes in vitro and in vivo. PMID- 8484728 TI - Rapid cellular removal of a membrane-inserted foreign polypeptide. AB - We have developed a system that makes it possible to study the fate of a foreign polypeptide that is inserted in the plasma membrane. Diphtheria toxin is a bacterial protein toxin that, upon acidification, has the ability to insert into the plasma membrane from the outside of eukaryotic cells. We present results that indicate endocytic uptake and degradation of the diphtheria toxin B-fragment after insertion into the membrane of Vero cells. The degradation rate of the fragment was found to be very high (t1/2 = 6 min) and dependent on cleavage of the extracellular part of the polypeptide with protease. Degradation was strongly inhibited in ATP-depleted cells, as well as at temperatures below 18 degrees C, and it was partially inhibited when the cytosol was acidified to block endocytosis from clathrin-coated pits. Degradation was also reduced in the presence of NH4Cl. The results indicate that the inserted and cleaved B-fragment is degraded by a process requiring endocytosis and transport to late endosomes or to lysosomes. PMID- 8484729 TI - Substitution of His-181 by alanine in yeast phosphoglycerate mutase leads to cofactor-induced dissociation of the tetrameric structure. AB - The structure and stability of a mutated yeast phosphoglycerate mutase in which His-181 has been replaced by alanine have been studied. The secondary, tertiary and quaternary structures of the mutant enzyme in the absence of ligands are essentially identical to those of the wild-type enzyme as revealed by c.d., fluorescence and cross-linking studies. The mutant enzyme is slightly less stable than the wild-type enzyme towards denaturation by guanidium chloride (GdnHCl). On addition of cofactor 2,3-bisphosphoglycerate, the wild-type enzyme shows increased stability towards GdnHCl. However, addition of cofactor causes dramatic changes in the structure of the mutant enzyme, leading to dissociation of the tetrameric form to dimeric and monomeric species. PMID- 8484730 TI - Determination of the order of substrate addition to MspI DNA methyltransferase using a novel mechanism-based inhibitor. AB - The cloning and overexpression of the MspI DNA methyltransferase as a functional fusion with glutathione S-transferase is described. The fusion enzyme retains full biological activity and has been used to investigate the interaction of substrates and inhibitors with MspI DNA methyltransferase. The fusion enzyme has been purified to homogeneity in a single step on GSH-agarose and is free from contaminating exonuclease activity. The enzyme can be photolabelled with S adenosyl-L-methionine and the level of incorporation of label is enhanced by the presence of a nonspecific DNA duplex. In the presence of a cognate oligodeoxynucleotide, no photolabelling was observed since methyl transfer occurs instead. The inclusion of a mechanism-based inhibitor of C-5 deoxycytidine DNA methylation (an oligodeoxynucleotide containing the base 2-pyrimidinone-1-beta-D 2'-deoxyribofuranoside in the position of the deoxycytidine to which methyl addition occurs), which is thought to form a covalent interaction with the reactive cysteine of such enzymes, led to an enhancement of S-adenosyl-L methionine photolabelling which suggests that, in contrast with results obtained with EcoRII DNA methyltransferase [Som and Friedman (1991) J. Biol. Chem. 266, 2937-2945], methylcysteine is not the photolabelled product. The implications of the results obtained with this mechanism-based inhibitor are discussed with respect to other C-5-specific DNA methyltransferases. Gel-retardation assays in the presence of cognate oligodeoxynucleotides that contain the reactive pyrimidinone base in place of the deoxycytidine target base are described. These demonstrate that most probably a stable covalent bond is formed between the methyltransferase and this oligodeoxynucleotide. However, the alternative of extremely tight non-covalent binding cannot be rigorously excluded. Furthermore, the results from these experiments indicate that the reaction mechanism proceeds in a manner similar to that of HhaI DNA methyltransferase with sequence-specific DNA binding being followed by addition of S-adenosyl-L-methionine and concomitant isomerization of the ternary complex leading to methyl transfer. S-Adenosyl-L homocysteine appears to inhibit the reaction pathway as a result of either competition with the methyl donor and potentiation of a high-affinity interaction between the enzyme and DNA in an abortive ternary complex or through an allosteric interaction. PMID- 8484731 TI - Transgenic mice over-producing putrescine in their tissues do not convert the diamine into higher polyamines. AB - We recently described a transgenic mouse line over-expressing the human ornithine decarboxylase gene virtually in all tissues. Despite strikingly elevated tissue putrescine concentrations, no or minimal changes were found in the levels of the higher polyamines spermidine and spermine. We have now extended these studies by further increasing tissue putrescine with the aid of 5-fluoromethylornithine, a specific inhibitor of ornithine transaminase and hence the catabolism of L ornithine. As a result of the treatment with the latter drug, the concentration of putrescine was further increased by a factor of 2-3 without any changes in the concentrations of spermidine and spermine. In the testis of transgenic mice treated with 5-fluoromethylornithine, the concentration of putrescine was nearly 60 times that in non-transgenic untreated animals, yet the concentration of spermidine was only 1.5-fold higher. A similar small increase in brain spermidine was accompanied by a 40-fold elevation in the concentration of putrescine. The apparent blockade between putrescine and spermidine was in all likelihood not attributable to an inhibition of S-adenosylmethionine decarboxylase, the rate controlling enzyme in the biosynthesis of spermidine and spermine. Our results are more compatible with the view that in non-dividing adult tissues putrescine is sequestered through some unknown mechanisms in a way that makes it unavailable for the synthesis of the higher polyamines. PMID- 8484732 TI - Direct observation of hexokinase translocation in stimulated macrophages. AB - 1. Fluorescence imaging of antibodies was used to show that phorbol 12-myristate 13-acetate (PMA) induces a 4-fold increase in the amount of hexokinase relative to the control in the cortical shell of rat peritoneal macrophage cytosol adjacent to the plasma membrane, and a corresponding depletion in the amount of hexokinase in the central core of the cytosol. However, there was no significant PMA-dependent change in the distribution of glucose-6-phosphate dehydrogenase. 2. Cytochalasin D, an inhibitor of actin microfilament polymerization, prevented the PMA-induced hexokinase translocation and also reduced the PMA-dependent increases in 2-deoxy-D-glucose transport and glucose-dependent PMA-stimulated superoxide production. 3. PMA caused a contraction of the width of the cortical F-actin zone. Cytochalasin D caused some dispersal of F-actin within the cell, increasing the density of F-actin within the central cytosolic core and causing aggregation of the F-actin within the cortex. These data are consistent with the view that PMA induces attachment of hexokinase to microfilaments within the cortical zone adjacent to the cell membrane of macrophages, and cytochalasin D prevents this attachment. This is the first direct demonstration of the translocation of hexokinase to the plasma membrane in activated cells, and supports the view that enhanced hexokinase activity in the cortical region of the cytosol is an important early component of the macrophage activation process. PMID- 8484733 TI - Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation. Some fundamental differences in proposed mechanisms of glucose oxidation and oxidant production. AB - Modification of human serum albumin (HSA) with formaldehyde resulted in a loss of 75% of available lysine residues, but there was no change in histidine content or susceptibility to free-radical-mediated fragmentation. The modified HSA appeared resistant to glycation and glucose-mediated fragmentation. Native HSA inhibited oxidant production by free glucose, as assessed by the hydroxylation of benzoic acid, but modified HSA had little effect. Thus the oxidation of free glucose appeared to be inhibited by glycatable protein, but not by unglycatable protein. Also, a close proximity of glucose to protein (decreased in the case of modified HSA) would seem to be a prerequisite for glucose-mediated protein fragmentation. This latter observation, in particular, led us to examine the role of oxidation of glucose attached to HSA in the production of reactive oxidants and subsequent molecular damage. Glycated HSA, washed free of unbound glucose, became fragmented and generated oxidants capable of hydroxylating benzoic acid and oxidizing cholesteryl linoleate-HSA complexes. Significant levels of benzoate hydroxylation and HSA fragmentation occurred with HSA (10 mg/ml) containing 3.3 mol of glucose bound/mol of HSA. This is equivalent to incubation of 10 mg/ml native HSA with 0.66 mM glucose, conditions which lead to little fragmentation or oxidant formation. The oxidative activity of glycated HSA was dependent on transition metal concentration. The level of protein-bound glucose appeared to decrease during the oxidant production and protein fragmentation. Thus glucose can oxidize and generate reactive oxidants, whether in solution or attached to protein. We discuss which is the more likely mechanism of glucose oxidation under the near physiological conditions used to study the effects of protein exposure to glucose in vitro. PMID- 8484734 TI - The mechanism of action of DD-peptidases: the role of tyrosine-159 in the Streptomyces R61 DD-peptidase. AB - Tyrosine-159 of the Streptomyces R61 penicillin-sensitive DD-peptidase was replaced by serine or phenylalanine. The second mutation yielded a very poorly active protein whose rate of penicillin binding was also drastically decreased, except for the reactions with nitrocefin and methicillin. The consequences of the first mutation were more surprising, since a large proportion of the thiolesterase activity was retained, together with the penicillin-binding capacity. Conversely, the peptidase properties was severely affected. In both cases, a drastic decrease in the transferase activity was observed. The results are compared with those obtained by mutation of the corresponding residue in the class A beta-lactamase of Streptomyces albus G. PMID- 8484735 TI - Co-purification of human serum lipoamidase and biotinidase: evidence that the two enzyme activities are due to the same enzyme protein. AB - A more than 20000-fold purification of human serum lipoamidase is described. This was accomplished by (NH4)2SO4 precipitation and chromatography on DEAE-Sepharose, Blue Sepharose CL-6B and phenyl-Sepharose CL-4B, followed by preparative isoelectric focusing (IEF) and finally by gel-permeation chromatography. Co precipitation and co-chromatography of lipoamidase and biotinidase activities with equal yields and purification were obtained in all the purification steps, indicating that lipoamidase and biotinidase activities in human serum are due to the same enzyme protein. After preparative IEF, two fractions with both lipoamidase activity and biotinidase activity were found at pI 4.0 and pI 4.4 respectively. The molecular mass of the enzyme was found to be 76 kDa. When 2 mercaptoethanol was used instead of cysteine as stabilizer during the purification procedure, only one major form (pI 4.0) of the enzyme was obtained after preparative IEF. By addition of cysteine, this form was transformed to an enzyme with pI 4.4, indicating that this latter form is a cysteine adduct, produced during the IEF procedure. PMID- 8484736 TI - Site-directed mutagenesis of mouse steroid 7 alpha-hydroxylase (cytochrome P 450(7) alpha): role of residue-209 in determining steroid-cytochrome P-450 interaction. AB - We have cloned a cDNA encoding mouse steroid 7 alpha-hydroxylase P450(7) alpha (cytochrome P-450(7) alpha) and expressed it in Saccharomyces cerevisiae. Mouse P450(7) alpha is 70% identical in its amino acid sequence with the mouse steroid 15 alpha-hydroxylase P450(15) alpha (2A4). The Leu at position 209 of P450(15) alpha is the most important residue to determine the steroid hydroxylase activity of the P450 [Lindberg and Negishi (1989) Nature (London) 339, 632-634]. The P450(7) alpha contains Asn at the position corresponding to the Leu-209 of P450(15) alpha, although both P450s hydroxylate testosterone. The CO-reduced P450(7) alpha complex is unstable, so that it is quickly converted into the inactive P420, whereas the P450(15) alpha is very stable. The P450(7) alpha, however, is stabilized either by addition of testosterone or by a mutation of Asn 209 to Leu. The mutant P450(7) alpha displays a 17-fold lower Vmax. value than the wild-type enzyme. Unexpectedly, it also has 3-fold lower Km and Kd values. Residue 209 in P450(7) alpha, therefore, appears to be located at a critical site of the haem-substrate-binding pocket. Corticosterone inhibits the testosterone 7 alpha-hydroxylase activity of the wild-type P450(7) alpha, whereas it does not inhibit the mutant P450(7) alpha. Conversely, the P450(15) alpha activity becomes inhibited by corticosterone upon the replacement of Leu-209 by Asn. In addition, this mutation increases the corticosterone 15 alpha-hydroxylase activity of P450(15) alpha at least 20-fold. Whereas the inhibition by corticosterone depends on the presence of Asn at position 209, deoxycorticosterone inhibits the activities of the P450s regardless of the type of residue at 209. The results indicate, therefore, that the identity of residue 209 determines the affinity as well as specificity of steroid binding to both P450(7) alpha and P450(15) alpha. PMID- 8484737 TI - Arthrobacter D-xylose isomerase: protein-engineered subunit interfaces. AB - Mutants of Arthrobacter D-xylose isomerase were constructed in which one or two disulphide bridges or additional salt bridges were introduced at the A-A* subunit interfaces. These showed no change in enzyme activity or stability compared with the wild-type enzyme. However, a Tyr253 mutant in which a disulphide bridge was introduced at the A-B* subunit interface showed reduced thermostability that was identical in both oxidized and reduced forms, and also reduced stability in urea. X-ray-crystallographic analysis of the Mn(2+)-xylitol form of oxidized Y253C (the Tyr253-->Cys mutant) showed a changed conformation of Glu185 and also alternative conformations for Asp254, which is a ligand to the Site-[2] metal ion. With fructose, Mg(2+)-Y253C has a similar Km to that of the wild-type, and its Vmax. is also similar below pH 6.4, but declined thereafter. In the presence of Co2+, Y253C has lower activity than wild-type at all pH values, but its activity also declines at alkaline pH. These results suggest that electrostatic repulsion from the new position of Glu185 causes Asp254 to move when His219 is unprotonated, thereby preventing M2+ binding at Site [2]. These results also suggest that subunit dissociation does not lie on the pathway of thermal inactivation of D xylose isomerase, but that movements of active-site groups are a trigger for conformational changes that initiate the unfolding process. PMID- 8484738 TI - Quantitative determination of the steady-state kinetics of multienzyme reactions using the algebraic rate equations for the component single-enzyme reactions. AB - Methods are given whereby the steady-state kinetic characteristics of multienzyme reactions consisting of individual single-enzyme reactions linked by freely diffusible intermediates can be determined quantitatively from the experimentally determined complete algebraic rate equations for the individual reactions. The approach is based on the fact that a valid steady-state rate equation for such a multienzyme reaction, in terms of the rate equations for the individual reactions, can be obtained simply from knowledge of the relative rates of the individual reactions when the multienzyme reaction is in the steady state. A number of model multienzyme reactions, which differ as to structural arrangement of the individual reactions, are examined by this approach. Simple mathematical methods which are applicable to most of these models are given for direct calculation of dependent variables. It is either pointed out or demonstrated with Mathematica that the rate equations for all of these models can be handled very easily with the aid of a personal computer equipped with appropriate equation solving software. Since the approach permits evaluation of all dependent variables for any specific combination of values for the kinetic parameters and independent variables, numerical values for the flux control coefficients of the individual enzymes can be obtained by direct calculation for a wide variety of conditions and can be compared with those obtained according to the methods of Metabolic Control Analysis. Several such comparisons have been made and in all cases identical results were obtained. The intuitive notion that the individual enzymes of a multienzyme reaction would be equally rate limiting if the total amount of enzyme were being used with maximum efficiency is tested and shown to be incorrect. In the course of this test the flux control coefficient for the individual enzymes were found to be appropriate indicators of relative rate limitation or control by the enzymes and to account properly for differences in specific activity among the enzymes. PMID- 8484739 TI - The sub-cellular localization of annexin V in cultured chick-embryo fibroblasts. AB - The Ca(2+)- and phospholipid-binding protein, annexin V, has been shown by an immune assay to represent 0.4% of total cell protein in cultured chick-embryo fibroblasts. Immunofluorescent localization studies indicate that in primary cultures the protein is abundant in the cytoplasm of the cells and also extends into the nucleus. Nuclear staining is no longer detectable, however, in approx. 25% of the cells following sub-culture. Sub-populations of annexin V are associated with cytoskeletal structures and with the inner face of the plasma membrane in a Ca(2+)-independent manner. In addition, we report results indicating the secretion of annexin V from this cell type. PMID- 8484740 TI - Isolation, characterization and localization of annexin V from chicken liver. AB - Annexin V has been purified from chicken liver; 40 mg of annexin V was obtained per kg of tissue. In contrast with mammalian liver, very little annexin VI was obtained. Surprisingly, chicken liver annexin V resembles mammalian annexin IV in its M(r) (32,500) and its isoelectric point (5.6), but amino-acid-sequence analysis demonstrates identity with chicken annexin V (anchorin CII). It binds to phospholipids in a Ca(2+)-dependent manner with free-Ca2+ concentrations for half maximal binding to phosphatidylserine and phosphatidic acid of 10 microM; phosphatidylethanolamine of 32 microM and phosphatidylinositol of 90 microM. No binding to phosphatidylcholine was observed at Ca2+ concentrations up to 300 microM. In isolated liver membranes a significant proportion of annexin V was not extractable with EGTA but could only be extracted with Triton X-100, suggesting the existence of a tightly membrane-associated form of annexin V. A specific antiserum to chicken annexin V was used to localize the protein in adult and embryonic chicken liver. In the adult, annexin V was highly concentrated in epithelial cells lining the bile ducts, and along the bile canaliculi. In embryonic liver, strong staining of the bile-duct epithelial cells was again evident, and in addition, endothelial cells were strongly immunoreactive. PMID- 8484741 TI - Different N-terminal forms of alpha 2-plasmin inhibitor in human plasma. AB - Mature alpha 2-plasmin inhibitor in human plasma has 12 more N-terminal residues than hitherto anticipated. The first residue is the methionine at position 28, downstream from the N-terminus of the pre-protein. The cDNA sequence predicts that the site cleaved upon formation of the mature inhibitor is a typical signal peptidase recognition site. The mature inhibitor (464 residues) and the previously reported, and presumably degraded, form with N-terminal asparagine (452 residues), are present in plasma in about equal amounts. They both form a stable complex with plasmin. Recent studies on a recombinant alpha 2-plasmin inhibitor suggest that the 12 additional residues have functional implications [Sumi, Ichikawa, Nakamura, Miura and Aoki (1989) J. Biochem. 106, 703-707]. PMID- 8484742 TI - Identification, purification and characterization of a membrane-associated N myristoyltransferase inhibitor protein from bovine brain. AB - N-Myristoyl-CoA: protein N-myristoyltransferase (NMT) is the enzyme that catalyses the covalent transfer of myristic acid from myristoyl-CoA to the N terminal glycine residue of a protein substrate. Subcellular fractionation of bovine brain indicates that NMT activity was located in both the cytosolic and the particulate fraction of the cell. Removal of the particulate fraction resulted in a 2-fold enhancement of NMT activity. Reconstitution of the particulate fraction and cytosolic fraction resulted in inhibition of the elevated cytosolic NMT activity. These results indicated the existence of putative inhibitor(s) activity of NMT located in the particulate fraction of bovine brain. The inhibitor was stable to heat and was identified as a protein, on the basis of its susceptibility to the proteases trypsin and chymotrypsin. Protease degradation first required the delipidation of the particulate fraction. The inhibitor was purified to near-homogeneity by heat treatment, solvent extraction and Sephacryl S-300 gelfiltration column chromatography. The inhibitor was purified 630-fold from the particulate fraction with a 20% yield. The protein inhibitor had an apparent molecular mass of 92 kDa by gel filtration and 71 kDa by SDS/PAGE, indicating the protein is monomeric. The inhibitor did not interact directly with myristoyl-CoA and possessed no protease, thioesterase or demyristoylase activity. Purified inhibitor protein inhibited the formation of 1167 pmol of myristoyl-peptide/min per mg of protein. PMID- 8484743 TI - Constitutive and inducible profile of glutathione S-transferase subunits in biliary epithelial cells and hepatocytes isolated from rat liver. AB - The constitutive and inducible cytosolic glutathione S-transferase (EC 2.5.1.18) subunit compositions of parenchymal cells (hepatocytes) and biliary epithelial cells (BEC) from rat liver have been quantitatively analysed using reverse-phase h.p.l.c. Hepatocytes, analysed in the absence of non-parenchymal cells, expressed constitutively the following subunits, in order of their concentration: 3, 4, 2, 1a, 1b, 8, 6 and 10. BEC express constitutively only four of the GST subunits expressed by hepatocytes and these are, in order of their concentration: subunits 2, 7, 4 and 3. Notable differences from hepatocytes are that BEC completely lack the Alpha-class subunits 1a and 1b that are major subunits in hepatocytes, Mu class subunits make up a very low proportion of the total, and the Pi-class subunit 7 is a major subunit in BEC, whereas it is essentially absent from hepatocytes. For the first time, the effects of the inducing agents phenobarbitone (PB), beta-naphthoflavone (beta-NF) and ethoxyquin (EQ) have been characterized in a comprehensive and quantitative manner in both cell types. PB, beta-NF and EQ increased total GST protein in hepatocytes by approx. 2-fold, 3 fold and 4-fold respectively. Subunits significantly induced in hepatocytes were (in order of fold-induction): by PB, 1b > 8 > 3 > 2 > 4; by beta-NF, 1b > 8 > 2 > 3 > 4; and by EQ, 7 > 1b > 10 > 8 > 3 > 2 > 1a > 4. In BEC, neither PB nor beta NF had significant effects on the total amount of GST protein, although PB did significantly induce subunit 3 at the expense of other subunits. EQ increased total GST protein nearly 5-fold in BEC, subunits 7 and 3 being induced dramatically above constitutive levels. PMID- 8484744 TI - Recombinant truncated thrombospondin-1 monomer modulates endothelial cell plasminogen activator inhibitor 1 accumulation and proliferation in vitro. AB - The angiogenic and malignant phenotypes of hamster tumor cells are inversely correlated with the expression of an amino terminally truncated thrombospondin (TSP) subunit. In the present study, we have constructed a truncated TSP subunit from a human fibroblast cDNA library (rt-TSP1) and expressed it in Chinese hamster ovary (CHO) cells. Increased concentrations of plasminogen activator inhibitor-1 (PAI-1) were detected in endothelial cell conditioned medium following treatment with rt-TSP1. This rt-TSP1-induced increase in PAI-1 was neutralized by monoclonal antibodies to both TSP and TGF beta. rt-TSP1 also inhibits the proliferation of endothelial cells and this response is also neutralized by TSP and TGF beta antibodies. Serine and cysteine proteases inhibitors were used to determine if rt-TSP1 activated the latent TGF beta. However, these protease inhibitors did not neutralize the effect of rt-TSP1. The data indicate that the anti-angiogenic properties of TSP may be due to inhibition of the pericellular proteolysis required for endothelial cell migration and endothelial cell proliferation. PMID- 8484745 TI - Suppressive role of sialylated N-glycans in Fc receptor-mediated phagocytosis by macrophages. AB - By culturing with tunicamycin A1, an inhibitor of N-glycosylation, or by sialidase digestion, mouse monocytic cells P388D1 were induced to carry out Fc receptor-mediated phagocytosis of IgG-coated sheep red blood cells. There was no significant difference in the numbers of IgG-coated sheep blood cells bound to the cells at 4 degrees C before and after exposure to tunicamycin or sialidase. These results suggest that sialylated N-glycans expressed on the cell surface have a suppressive role in the induction of phagocytosis, and their decreased expression or reduced sialylation results in acquisition of the phagocytic ability of the cells by affecting some processes involved in the ingestion of the particles bound to Fc receptors. PMID- 8484746 TI - The ability of murine leukocytes to bind lipocortin 1 is lost during acute inflammation. AB - Lipocortin 1, a member of the annexin superfamily of calcium and phospholipid binding proteins, mediates some of the anti-inflammatory actions of the glucocorticoid hormones. Lipocortin 1 binds to the surface of murine peripheral blood monocytes and polymorphonuclear leukocytes (Kd estimate 2 x 10(-8) M) but not lymphocytes. Resident peritoneal macrophages exhibit binding (Kd estimate 1.3 x 10(-8) M) but lymphocytes do not. A 95-98% reduction in lipocortin 1 binding was observed to leukocytes obtained from air pouch or peritonitis models of inflammation. When given intravenously, lipocortin 1 binds rapidly to murine leukocytes within 5 min but disappears before 10 min, leaving the binding capacity of the cells unaltered. Modulation of lipocortin 1 binding sites could be an important step in regulating the function of inflammatory cells. PMID- 8484747 TI - Lipocortin 1 binding to human leukocytes correlates with its ability to inhibit IgG interactions with Fc gamma receptors. AB - The anti-inflammatory protein lipocortin 1 has been proposed as a mediator of some of the anti-inflammatory actions of glucocorticoid hormones. In view of reported glucocorticoid effects on leukocyte Fc gamma receptors, the effect of short-term lipocortin 1 pre-incubation on expression and IgG binding capacity of human Fc gamma receptors was examined in vitro. The formation of erythrocyte antibody rosettes, binding of fluoresceinated IgG ligand and the expression of three defined types of Fc gamma receptors were observed following lipocortin 1 treatment. Maximal inhibition of EA rosetting (70%) by peripheral blood mononuclear cells and a 30-50% inhibition of binding of fluoresceinated human IgG1 to purified human monocytes occurred in the presence of 400 nM lipocortin 1 (p < 0.01). However, there was no accompanying decrease in expression of the three known Fc gamma receptor types measured by specific monoclonal antibodies. Similar observations were made for peripheral blood polymorphonuclear cells. On the other hand, IgG binding was not inhibited by lipocortin 1 in lymphocytes or in a panel of cell lines which express Fc gamma receptors and none of these cell types had the capacity to bind lipocortin. PMID- 8484748 TI - Apolipoprotein E: binding to soluble Alzheimer's beta-amyloid. AB - Apolipoprotein E (apo E) is associated with Alzheimer's beta-amyloid (A beta) in senile plaques. A beta is now known to be a normal soluble peptide (sA beta) found in the cerebrospinal fluid (CSF) and other biological fluids. We have used synthetic A beta peptides bound to affinity membranes in order to determine whether apo E or any other amyloid associated protein will bind to these membranes, when they are bathed in CSF. Under these conditions apo E, as well as another apolipoprotein, apolipoprotein J (Apo J), bound to the membranes. Using ELISA and ligand binding studies, we found a high avidity binding of A beta peptides to apo E. This suggests that apo E, as well as other related proteins may bind not only amyloid A beta but also sA beta. This interaction may be critical in amyloid formation. PMID- 8484749 TI - Purification of a 28 kD non-aggregating tryptic peptide of the Duffy blood group protein. AB - Duffy blood group antigenic epitopes are located on a 35-43 kD integral membrane protein of the erythrocyte membrane. This protein functions as a receptor for the human malaria parasite, Plasmodium vivax. The Duffy protein has been difficult to purify because of its tendency to form aggregates. Here we describe purification of a 28 kD tryptic fragment of the Duffy protein and purification of an 18 kD de glycosylated form of the Duffy tryptic peptide using Thiopropyl Sepharose 6B chromatography and preparative SDS-PAGE. These Duffy-reactive peptides do not form aggregates and may prove amendable to protein sequencing. PMID- 8484750 TI - Isolation and characterization of four basic proteins from horse eosinophilic granules. AB - Four new basic proteins were isolated from horse eosinophils and purified. The eosinophils release these proteins after permeabilization with saponin and degranulation stimulized by guanosine 5'-O-thiotriphosphate. The proteins were separated and purified on a Superose P12- and a Mono S-column by fast protein liquid chromatography. The amino acid composition, the relative molecular mass, the isoelectric point and the partial N-terminal sequence of the four proteins were determined. Papain-activation and ribonuclease activity of the four proteins were tested for comparison with the human eosinophil basic granular proteins. The cytotoxicity of the hole granular extract and of the isolated basic proteins against Escherichia coli K12 was also studied. PMID- 8484751 TI - Studies of the relationship between cell proliferation and cell death. III. AP-1 DNA-binding activity during concanavalin A-induced proliferation or dexamethasone induced apoptosis of rat thymocytes. AB - In previous papers we started to investigate the possible relationship existing between cell proliferation and cell death. We reported that in rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment, an induction of c-fos and c-jun occurs with different but partially overlapping kinetics (Grassilli et al., BBRC, 1992, 188, 1261-1266). To test the hypothesis that, in both processes, the early induction of these nuclear oncogenes is necessary to allow the induction of later-expressed genes regulated at the transcriptional level by AP-1 complex, AP-1 DNA-binding activity was investigated in the aforementioned model. Indeed, we found that AP-1 is activated not only in proliferating but also in apoptotic cells, with a kinetics in accord with our data about c-fos and c-jun mRNA accumulation in the same experimental model. Moreover, our findings suggest that an interaction between AP-1 and glucocorticoid receptor also occurs in our model of dexamethasone-mediated apoptosis. PMID- 8484752 TI - Comparison of COS cell transfected AT1A and AT1B angiotensin II receptors and angiotensin II receptor isoforms in rat tissues using isoelectric focusing. AB - Rat adrenal AT1A and AT1B receptors from transfected COS-7 cells were labelled with 125I-Angiotensin II, solubilised, and run on isoelectric focusing gels. Receptors from rat tissues were treated similarly. COS-7 cell-expressed AT1A and AT1B receptors each produced a single peak of specific radioactivity at pI 6.8. Rat liver and rat ovary tissue preparations gave peaks at pI 6.8 and 6.5, respectively. In contrast, rat adrenal tissue preparations gave four peaks at pI 7.0, 6.8, 6.5, and 6.3. The additional isoforms found in the rat adrenal tissue preparations may represent post-translationally modified or novel receptors. PMID- 8484753 TI - Alteration of the product specificities of prenyltransferases by metal ions. AB - Effect of several kinds of metal ions on the chain-length distribution of reaction products of polyprenyl diphosphate synthases was investigated. In the presence of Co2+ or Mn2+ octaprenyl-, solanesyl- and decaprenyl diphosphate synthases gave a variety of polyprenyl products with the longest chains being shifted by one or two isoprene units longer than those of the products formed in the presence of Mg2+. Thus octaprenyl diphosphate synthase became to give solanesyl (C45) and decaprenyl (C50) diphosphates when Mg2+ is replaced with Co2+ or Mn2+. Similarly solanesyl diphosphate synthase produced C50- and C55- diphosphates in the presence of Co2+ or Mn2+, and decaprenyl diphosphate synthase gave C55- diphosphate as the longest product in the presence of Mn2+. More remarkable effects were observed with Mn2+ than with Co2+. PMID- 8484754 TI - Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant. AB - The organization of the human heparin-binding neurite outgrowth promoting factor (HBNF) gene is presented. Based on Southern analysis and the isolation of genomic DNA clones from a lambda phage library, the minimum size of the gene is 42 kb. Sequences comprising the HBNF mRNA are contained in five exons which account for the 1650 nt mRNA size observed by northern analysis. From the structure of the gene it is predicted that a variant human HBNF cDNA with a three basepair deletion is a result of alternative splicing at the acceptor site of exon 5. Evidence is presented that indicates the existence of a variant HBNF protein, des Ala119-HBNF, in bovine brain which has a corresponding amino acid deletion. This alternate form comprises approximately 20% of the total HBNF protein present in bovine brain. PMID- 8484755 TI - Transplasma membrane redox system in HL-60 cells is modulated during TPA-induced differentiation. AB - Besides its effect in inhibiting proliferation and inducing differentiation of HL 60 cells to macrophage-like cells, TPA also produces a transient increase of transplasma membrane redox activity and pyridine nucleotide levels and a shift in the NAD+/NADH ratio. After 24 h of incubation NADH ferricyanide reductase activity of isolated plasma membranes was significantly higher than that of plasma membrane from non-differentiated cells. This correlated with the enhanced short-term oxidation of NADH in response to ferricyanide by HL-60 cells incubated with TPA for 24 h. Since differentiated cells with similar levels of NADH showed different redox activities, the redox chain itself seems to be modulated during differentiation induced by TPA. PMID- 8484756 TI - Platelet-activating factor stimulates protein kinase C translocation in cerebral microvessels. AB - The effects of platelet-activating factor (PAF) on distribution of protein kinase C activity in brain microvessels have been examined. Our results indicate that PAF caused an increase of protein kinase C activity in membrane, accompanied by a loss of activity in the cytosol. This effect resulted to be dose-dependent and the translocation was evident after 30 min of PAF treatment. These results suggest that PAF could play a role in transport processes in the blood-brain barrier, involving protein phosphorylation by activation of protein kinase C. PMID- 8484757 TI - Molecular cloning of rat cytokine synthesis inhibitory factor (IL-10) cDNA and expression in spleen and macrophages. AB - Rat cytokine synthesis inhibitory factor (IL-10) was cloned. Like mouse and human IL-10 (mIL-10, hIL-10), rat IL-10 exhibits strong DNA and amino acid sequence homology to the open reading frame in the Epstein-Barr virus, BCRFI. The supernatant of COS-7 transfectants with rat IL-10 was found to inhibit the production of IFN-gamma by murine Th1 cells. A probe from the rat IL-10 was used in an RNase protection assay to demonstrate that IL-10 was expressed in LPS stimulated rat spleen and FACS-purified OX-42-reactive peritoneal macrophages. The production of IL-10 by macrophages, as shown in the current study, suggests that IL-10 may have an autocrine function in inflammation. PMID- 8484758 TI - Tissue-specific expression of rat light neurofilament promoter-driven reporter gene in transgenic mice. AB - We have produced nine transgenic mice lines carrying either 5 kbp or 407 bp of the 5' flanking sequence of the rat light neurofilament gene linked to the chloramphenicol acetyltransferase (CAT) structural gene. With the 5kb light neurofilament 5' flanking region governing the expression of CAT, reporter gene activity was detected not only in brain but also in the eye lens and skeletal muscle, yet not in other tissues. With the 407 bp construct, reporter gene activity was detected only in the brain, although expression was approximately one tenth of that found with the 5 kb 5' region. These results, together with earlier observations, indicate that the sequence -407 to -292 of the proximal promoter region for the light neurofilament gene or sequence +15 to +75 bp after the transcription initiation site is crucial for brain-specific expression of a fusion gene in transgenic mice. PMID- 8484759 TI - Plasma membrane dependent reduction of 2,4,6-trinitrotoluene by Phanerochaete chrysosporium. AB - A plasma membrane redox system of Phanerochaete chrysosporium was found to reduce 2,4,6-trinitrotoluene (TNT). Reduction required intact, live mycelia. No reduction was observed with either supplemented (NADPH, NADH or ATP) or unsupplemented extracellular or intracellular fractions, either under aerobic or anaerobic conditions. Reduction was inhibited by potassium ferricyanide, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium, carbonyl cyanide p trifluoromethoxyphenyl hydrazone, 2,4-dinitrophenol, sodium azide, and tetranitroblue tetrazolium but not by nitroblue tetrazolium, 2,3,5-triphenyl tetrazolium and blue tetrazolium. At higher pH, the rate of reduction as well as proton pumping was enhanced. PMID- 8484760 TI - Metabolism and detoxification of TNT by Phanerochaete chrysosporium. AB - Several lines of evidence suggest that TNT detoxification by Phanerochaete chrysosporium is through reduction. Rates of TNT reduction were directly correlated with mycelial mass and TNT concentration. Toxicity was inversely related to the amount of fungus. TNT toxicity was identical in both ligninolytic and nonligninolytic cultures. Rapid disappearance of the reduced metabolites coincided with production of the manganese-dependent peroxidases and mineralization of TNT was not observed until the lignin peroxidases were detected. PMID- 8484761 TI - Abundant production of nitric oxide from murine macrophages by direct stimulation of tumor cells. AB - By the coculture of tumor cells and resident murine peritoneal macrophages, we found that P1HTR tumor cells, which were the subline of P815 mastocytoma, stimulated syngeneic or allogeneic peritoneal macrophages to produce nitric oxide. This nitric oxide in turn kills P1HTR target cells. The cytotoxicity and nitric oxide production were completely abolished by the addition of L-arginine homologue NG-monomethyl-L-arginine. The original P815 tumor cells had only weak activity to stimulate macrophages to produce nitric oxide and were weekly killed by coculture of P815 and resident macrophages. Macrophage cell line, RAW264-7, was also stimulated to produce nitric oxide by P1HTR cells. The ability to stimulate macrophages to produce nitric oxide resided on the membranous fragment of P1HTR cells. PMID- 8484762 TI - Modification of energy metabolism and radiation response of a murine tumour by changes in nitric oxide availability. AB - The nitric oxide donor, SIN-1 and nitric oxide synthase inhibitor, nitro-L arginine were examined for their effects on energy metabolism using 31P magnetic resonance spectroscopy, and on radiation sensitivity in the transplantable murine tumour, SCCVII/Ha. SIN-1 at 2 mg/kg i.v. reduced Pi/total by 40-50% within 10 min and increased X-ray sensitivity 3 fold, consistent with increased tumour oxygenation. Nitro-L-arginine at 10 mg/kg i.v. increased Pi/total by 250% at 45 min and was maintained for at least 2 hr. Nitro-L-arginine also increased radiation resistance 3-5 fold, consistent with the induction of tumour hypoxia. The results indicate that tumour energy metabolism may be altered through drug induced modification of nitric oxide availability, and that these changes are sufficient to modify tumour sensitivity to X-rays. PMID- 8484763 TI - Homogeneous catalytic deuteration of fatty acyl chains as a tool to detect lipid phase transitions in specific membrane domains: a Fourier Transform Infrared spectroscopic study. AB - Synthetic phospholipid molecules have been deuterated by using a water soluble catalyst and deuterium gas. The physical state of both deuterated segments and unaffected bulk part of the lipid molecules can be monitored simultaneously by Fourier Transform Infrared Spectroscopy. It is shown on multilamellar phospholipid systems that the deuterated segments can be used as structural probes. Whereas the nu(C-H) frequencies represent an average conformational order along all the alkyl chains present, by following changes in nu(C-D) vibrations, mobility of those membrane domains deuterium labeled at specific depths in the hydrocarbon core can be estimated. The potential importance of this new approach in the study of biological membranes is discussed. PMID- 8484764 TI - Evidence for C-type natriuretic peptide production in the rat kidney. AB - To elucidate the physiological role of C-type natriuretic peptide (CNP) as a local mediator, we examined the production of CNP in the rat kidney. The content of CNP in the kidney was 0.47 +/- 0.02 [SE] fmol/mg wet weight and the major molecular form of CNP was CNP-53. An established cell line from the rat kidney, NRK-52E cell, secreted CNP at a rate of 9.15 +/- 0.96 fmol/24 hr/mg protein. Furthermore, CNP mRNA was detected in the rat kidney and NRK-52E cell utilizing reverse transcription-polymerase chain reaction (RT-PCR). On the other hand, ANP in the rat kidney (2.56 +/- 0.19 fmol/mg wet weight) had the molecular form of alpha-ANP, but ANP mRNA was not detected by RT-PCR. No BNP immunoreactivity was found in the rat kidney, although BNP mRNA was detected by RT-PCR. These results indicate that only CNP among the natriuretic peptides is produced in significant amounts in the rat kidney under normal physiological conditions and that renal parenchymal cells may produce CNP. PMID- 8484765 TI - The major mutation among Japanese patients with infantile Tay-Sachs disease: a G to-T transversion at the acceptor site of intron 5 of the beta-hexosaminidase alpha gene. AB - A G-to-T substitution at the 3'-splice site of intron 5 in the beta hexosaminidase alpha-subunit gene has been identified among Japanese patients with infantile Tay-Sachs disease. Of the 24 patients from 24 unrelated families, 15 were homozygous and 8 were heterozygous for this mutation (38/48 mutant alleles). The mutation causes a splicing abnormality, and the resultant mRNA lacks the exon 6 sequence. Northern blot analysis showed a single band of mRNA, distinctly shorter in size and slightly smaller in quantity than normal. Since exon 6 consists of 102 nucleotides, the mRNA should generate a beta hexosaminidase alpha-subunit missing 34 amino acids in the middle but otherwise normal in the primary structure. It must be catalytically inactive or unstable, or both. The high frequency of this mutation among the Japanese patients with the infantile form of Tay-Sachs disease and its apparent absence outside of Japan suggests that this mutation may have originated in Japan. PMID- 8484766 TI - Dynamic infrared imaging of cardiac pacemaker induction and cortical muscle contractions of embryonic avian heart. AB - The dynamic nature of electromagnetic (EM) pacemaker induction of cardiac tissue contractions in cultured embryonic avian heart was analyzed with noninvasive real time infrared (IR) imaging at normal physiological conditions. This technique was used to visualize the endogenous sarcomeric Ca2+ oscillation induced cortical IR EM radiation within an 8-12 micron IR emission spectra. The results reported here establishes the fact that cardiac energetics produce topographical IR-EM radiation that can be visualized directly without invasive dyes or external light sources to noninvasively study the mechanisms of striated muscle tissue morphogenesis. Since IR microscopy capitalizes on imaging the inherent radiation from biological molecules in tissue, no external light sources are needed to reflect a visual spectrum. These findings provide the framework for future noninvasive investigations and characterizations of the endogenous energetics in living cells. PMID- 8484767 TI - The primary structure of rat ribosomal protein L29. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L29 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L29 has 155 amino acids, the NH2-terminal methionine is removed after translation of the mRNA, and has a molecular weight of 17,183. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 20 to 22 copies of the L29 gene. The mRNA for the protein is about 750 nucleotides in length. Rat L29 is related to yeast ribosomal protein YL43. PMID- 8484768 TI - The primary structure of L37--a rat ribosomal protein with a zinc finger-like motif. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L37 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L37 has 96 amino acids, the NH2-terminal methionine is removed after translation of the mRNA, and has a molecular weight of 10,939. Ribosomal protein L37 has a single zinc finger-like motif of the C2-C2 type. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 13 or 14 copies of the L37 gene. The mRNA for the protein is about 500 nucleotides in length. Rat L37 is related to Saccharomyces cerevisiae ribosomal protein YL35 and to Caenorhabditis elegans L37. We have identified in the data base a DNA sequence that encodes the chicken homolog of rat L37. PMID- 8484769 TI - Biotransformation of pravastatin sodium (I). Mechanisms of enzymic transformation and epimerization of an allylic hydroxy group of pravastatin sodium. AB - One of the major metabolites, R-416(3'alpha-OH), of pravastatin sodium(PV, 6'beta OH), and a minor metabolite, R-418 (6'alpha-OH), were produced in rat liver cytosol in the presence of adenosine 3'-phosphate 5'-phosphosulfate as a cofactor. The reactions were inhibited by the inhibitors for sulfotransferases, and 18OH was introduced to the 3'alpha- and 6'alpha-positions of R-416 and R-418, respectively, by incubation with H2 18O. These results strongly suggested that PV was metabolically activated by sulfation at the 6'beta-hydroxy group by sulfotransferases, followed by nucleophilic attack of hydroxy anions at the 3'alpha- or 6'alpha-position, to give R-416 or R-418, respectively. PMID- 8484770 TI - Early and selective induction of apoptosis in human leukemic cells by the alkyl lysophospholipid ET-18-OCH3. AB - We have found that the alkyl-lysophospholipid 1-octadecyl-2-methyl-rac-glycero-3 phosphocholine (ET-18-OCH3) was able to induce apoptosis in human promyelocytic HL-60 leukemic cells, as evidenced by the internucleosomal degradation of the cellular DNA into the characteristic 180-200 bp DNA fragments. This effect was observed after short periods of cell incubation (6 h) with low doses of ET-18 OCH3 (3 micrograms/ml). Furthermore, we found that ET-18-OCH3 also induced rapidly apoptosis in human promonocytic U937 leukemic cells. In contrast, 3T3 fibroblasts were resistant to the alkyl-lysophospholipid. ET-18-OCH3 induced apoptotic cell death of tumor epithelial-like HELA cells, but this process required prolonged times of incubation. These data demonstrate that ET-18-OCH3 promotes a rapid and selective programmed cell death in human leukemic cells, providing an explanation to the previously described cytotoxic effects of this compound on leukemic cells. PMID- 8484771 TI - Nitric oxide-regulated endogenous ADP-ribosylation of rod outer segment proteins. AB - Both membrane and cytosolic fractions of retinal rod outer segments contain ADP ribosylases that modify proteins in the respective fractions. Nitroprusside and endogenously produced NO regulate the activities of these ADP-ribosylases. The ADP-ribosylation of the membrane proteins of molecular weight 116K, 66K and 46K is inhibited by NO and nitroprusside, while that of the 38K cytosolic protein and the 39K membrane-associated protein is activated. The 39K protein is identified as the alpha-subunit of G-protein. The ADP-ribosylation of this protein is activated 6 to 11-fold by NO suggesting that NO may play a significant role in modulating the activity of G-protein in visual transduction. PMID- 8484772 TI - Mammalian mitochondrial DNA sequences can function as in vivo bacterial transcription terminators. AB - We have used a prokaryotic terminator identification vector, pDR721, to isolate regions from rat mitochondrial DNA (mtDNA) that can act as transcription terminators in vivo. Three independent fragments having terminator capability have been mapped to three general regions of the mitochondrial genome. Two terminators, pRMT1 and pRMT3, are found within and around the D-loop and cytochrome b gene, respectively, while the third, pRMT5, is located at the 3'-end of the 16S ribosomal RNA gene. After subcloning into host cells which carried temperature sensitive mutations in the termination factor, rho protein, galactokinase assays at the permissive and non-permissive temperatures suggested that pRMT3 acted as a rho-independent termination element while the other two, pRMT1 and pRMT5, were dependent on rho protein (or a rho-like protein) for efficient transcription termination. PMID- 8484773 TI - Polyamine regulation of S-adenosylmethionine decarboxylase synthesis through the 5'-untranslated region of its mRNA. AB - The effect of the 5'-untranslated region (5'-UTR) of S-adenosylmethionine decarboxylase (SAMDC) mRNA and of polyamines on the translation of SAMDC mRNA was studied in a rabbit reticulocyte cell-free system. Using synthetic SAMDC mRNAs possessing different sizes of 5'-UTR, it was shown that nucleotides in the 5'-end of 5'-UTR were responsible for polyamine inhibition at high concentrations. Existence of the 5'-end nucleotides decreased SAMDC synthesis and slightly increased the degree of polyamine stimulation of the synthesis at low concentrations. When poly(A)+ RNA from mouse SAMDC-overproducing cells was used as mRNA, the degree of polyamine inhibition at high concentrations was nearly the same, but that of polyamine stimulation at low concentrations was greater than with synthetic SAMDC mRNAs. The reason for this difference is discussed. PMID- 8484774 TI - Analogues of butyric acid that increase the expression of transfected DNAs. AB - Butyric acid has many strong effects on gene expression in mammalian and viral systems, as well as in increasing the expression of recombinant DNAs artificially introduced into cultured cells. We screened 14 analogues of butyric acid for their ability to upregulate expression from 3 different recombinant chloramphenicol acetyltransferase expression vectors stably integrated into NIH 3T3 cells that had been transformed by calcium phosphate transfection or electroporation. Butyric acid, 2-bromobutyric acid, 3-bromopropionic acid, 3 mercaptopropionic acid, vinylacetic acid, and butyraldehyde were found to upregulate human immunodeficiency viral long terminal repeat-, SV40 early gene promoter-, and glucocerebrosidase promoter-directed expression of heterologous genes in cultured cells. Three other analogues had lesser effects; and 6 additional analogues had very little, if any, effect. PMID- 8484775 TI - Molecular characterisation of a human aryl sulfotransferase cDNA. AB - A full-length aryl sulfotransferase cDNA was isolated from a human liver cDNA library. It was 1155 bp long containing a coding region of 885 basepairs encoding a cytosolic protein (M(r) 34178 Da) of 295 amino acids. This human cDNA shared 80% homology to the rat aryl sulfotransferase cDNA, 58% to the bovine and rat oestrogen sulfotransferase cDNAs, 53% to the rat hydroxysteroid sulfotransferase cDNA and 51% to the human liver dehydroepiandrosterone sulfotransferase cDNA over its whole 885 bp coding region. The deduced amino acid sequence of this human cDNA was 79% homologous to that of the rat aryl sulfotransferase cDNA and the putative common-substrate binding site motif GXXGXXK of the sulfotransferases has been conserved in this human amino acid sequence. At least two sizes of this human aryl sulfotransferase mRNA were detected in the human liver and lung. PMID- 8484776 TI - Activation of MCP-1 gene expression is mediated through multiple signaling pathways. AB - Multiple signal transduction pathways including protein kinase C, tyrosine phosphorylation, and an independent third signaling mechanism are involved in the activation of monocyte chemotactic protein-1 gene. Northern blot analysis showed that the incubation of endothelial cell with dioctanoylglycerol induced maximum level of monocyte chemotactic protein-1 transcripts. The TPA-induced monocyte chemotactic protein-1 expression was abolished by treating the cells with both staurosporine and genistein; however, only a portion of the LPS-induced expression was inhibited by staurosporine/genistein. This is in accordance with the observation that LPS induced the expression of monocyte chemotactic protein-1 in desensitized cells. Thus, a third signal transduction pathway other than protein kinase C or tyrosine kinase is involved in the LPS-induced monocyte chemotactic protein-1 expression in human endothelial cell. PMID- 8484777 TI - Thiol groups are involved in NADH-ascorbate free radical reductase activity of rat liver plasma membrane. AB - Plasma membranes purified by two-phase partition from rat liver showed an NADH ascorbate free radical reductase activity of about 14 nmoles NADH oxidized/min/mg protein. This activity was inhibited by N-ethyl maleimide, iodoacetate and iodoacetamide, reagents that covalently block thiol groups. NADH-ascorbate free radical reductase was also inhibited by reduced glutathione and the inhibitions observed with blocking reagents and reduced compounds were additive. These results support the involvement of sulphydryl groups in NADH-AFR reductase and point out the idea that a balance between reduced sulfhydryls and oxidized disulfides is required for the optimal function of this activity, considered as part of the transplasma membrane electron transport system. PMID- 8484778 TI - p53 gene is up-regulated during skeletal muscle cell differentiation. AB - Differentiation of cells in the mouse myogenic cell line C2, or a primary culture of chicken satellite cells was induced by low serum levels in the growth medium. Endogenous wild-type p53 mRNA was substantially expressed after approximately 5 h of incubation. Induction of p53 mRNA expression was also observed in cells treated with 10(-8) M retinoic acid, after 18 h of incubation. In both cases, the increase in p53 mRNA was transient. c-fos mRNA levels decreased rapidly and were barely detectable after 2 h of exposure to retinoic acid. The down-regulation of c-fos confirms its role in muscle cell differentiation, whereas the up-regulation of wild-type p53 suggests its role during this process. PMID- 8484779 TI - Bacterially expressed murine CSF-1 possesses agonistic activity in its monomeric form. AB - CSF-1 is a dimeric peptide growth factor, stabilized by disulfide bonds. We expressed mouse CSF-1 in bacteria as a fusion protein either with glutathione S transferase (GST) or with a six histidine tag (His-tag). Large amounts of recombinant material were obtained and purified by a single affinity chromatography step. Purified CSF-1-His-tag monomers efficiently dimerized in vitro, but the presence of variable amounts of GST-moiety in CSF-1 preparations obtained by thrombin cleavage of GST-fusion proteins (thrombin-released CSF-1) interfered with dimerization. However, the thrombin-released CSF-1 monomers possessed agonistic activity, being capable of stimulating tyrosine phosphorylation of the CSF-1 receptor and of an array of cellular proteins in living macrophages and of supporting their growth. These results show that CSF-1 dimerization is not essential for receptor activation in vivo. PMID- 8484780 TI - Comparison of the disulfide bond arrangements of human recombinant and bovine brain heparin binding neurite-promoting factors. AB - Heparin binding neurite-promoting factor (HBNF) is a highly basic 136 amino acid protein containing 10 cysteine residues. We have determined the redox status and the disulfide arrangement of the cysteine residues in HBNF from bovine brain and refolded human recombinant protein produced in E. coli. Our data indicate that all 10 cysteines are involved in disulfide bond formation. The disulfide linkages of human recombinant and bovine brain HBNF, as determined after proteolytic digestions of the non-reduced proteins by peptide mapping and sequence analysis are: Cys15-Cys44, Cys23-Cys53, Cys30-Cys57, Cys67-Cys99 and Cys77-Cys109. Thus, recombinant HBNF has the same disulfide arrangement as the native brain-derived protein. PMID- 8484781 TI - Identification of active-site residues in Aspergillus ficuum extracellular pH 2.5 optimum acid phosphatase. AB - Primary structure elucidation of peptides generated by cyanogen bromide, endoproteinase Glu-C, and clostripain cleavage of an Aspergillus ficuum extracellular pH optimum 2.5 acid phosphatase identified a region which contains the active site of the enzyme. The 23-residue segment contains the fragment RHGXRXP, which is homologous to acid phosphatase from Saccharomyces spp., Aspergillus ficuum, mammals, and bacteria. Homologous or conservative substitutions are observed in the 10-amino acid fragment preceding this region. PMID- 8484782 TI - Thioredoxin from activated macrophages as a trophic factor for central cholinergic neurons in vitro. AB - The conditioned medium from gamma-interferon-stimulated macrophages elevated the choline acetyltransferase activity in mouse septal neurons as well as in cholinergic hybrid cell lines SN6.10.2.2 in vitro. After purification and sequencing, the active fraction was identical to thioredoxin (TRX), and the neurotrophic activity of recombinant TRX was confirmed. PMID- 8484783 TI - Strand breaks in DNA induced by a thiol/Fe(III)/O2 mixed-function oxidase system and its protection by a yeast antioxidant protein. AB - Strand breaks can be produced in pBluescript plasmid DNA and calf thymus DNA by a mixed-function oxidase (MFO) system comprised of Fe3+, O2, and dithiothreitol as an electron donor. Superoxide dismutase does not block this damage whereas a 27 KDa yeast antioxidant protein specifically inhibits strand breaks in DNA induced by the dithiothreitol MFO system. In contrast, this protein does not inhibit strand breaks in DNA induced by an ascorbate MFO system although catalase inhibits damage in DNA caused by both MFO systems. Based on the specificity of this protein, we propose that the antioxidant protein functions as a sulfur radical scavenger. PMID- 8484784 TI - Differentiation of monocytoid THP-1 cells with phorbol ester induces expression of prostaglandin endoperoxide synthase-1 (COX-1). AB - Prostaglandin endoperoxide synthase (PGH synthase) is responsible for converting arachidonic acid to PGH2, the common precursor of prostaglandins. It has been shown previously that phorbol ester-induced differentiation of the THP-1 human monocytic leukemia cell line is accompanied by induction of PGH synthase enzyme and enhanced capacity to produce prostaglandins. However, the identity of the isoform of PGH synthase that is induced under these conditions has not been established. Northern and Western analyses revealed a dramatic increase in levels of PGH synthase-1 mRNA and protein levels within 24 hr after treatment of THP-1 cells with phorbol ester. No significant increase in PGH synthase-2 mRNA or protein was observed. The increases in PGH synthase-1 were accompanied by enhanced capacity of the cells to produce PGE2. These findings indicate that expression of PGH synthase-1 is greatly enhanced in THP-1 cells by treatment with an agent that induces differentiation. PMID- 8484785 TI - Lipoproteins induce expression of the early growth response gene-1 in vascular smooth muscle cells from rat. AB - Recently, we reported that low-density lipoprotein (LDL) induces in vascular smooth muscle cells (VSMCs) intracellular effects such as an elevation of intracellular free Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi). The early growth response gene-1 (Egr-1) has been identified as a transcription factor belonging to a class of immediate-early genes expressed upon growth, and/or differentiation signals in a large variety of cells and species. Here we show that LDL induces a dose-dependent expression of the Egr-1 mRNA with a maximum at 30 min. Experiments in the presence of the dihydropyridine calcium blocker isradipine suggest that the lipoprotein-induced Egr-1 mRNA induction occurs via a Ca2+ dependent pathway. To demonstrate whether these intracellular responses are only specific to LDL we examined the effects of high- and very low density lipoprotein (HDL and VLDL) on [Ca2+]i and expression of Egr-1 mRNA. The present results show that all lipoproteins induce expression of Egr-1 mRNA and elevation in [Ca2+]i in VSMCs. PMID- 8484786 TI - Induction of differential heat shock gene expression in heart, lung, liver, brain and kidney by a sympathomimetic drug, amphetamine. AB - Amphetamine, a sympathomimetic drug, can elevate the body temperature by causing enhancement of endogenous lipolysis. This study was designed to examine whether this drug could induce the expression of the genes of heat shock proteins (HSP) in different tissues. Subcutaneous administration of amphetamine (10 mg/kg wt) to the rats increased the rectal temperature of the rats to 42 degrees C within 60 min. After 3 hr rats were sacrificed; and heart, lung, liver, kidney and brain tissue were removed to examine the induction of mRNAs for HSPs by Northern blot analysis using cDNA probes of 27 kDa, 70 kDa and 89 kDa HSPs. The results of this study indicate striking regional and cell type differences in the pattern of induction of the HSP mRNAs by amphetamine suggesting that different organs and cell types respond differently to amphetamine. PMID- 8484787 TI - Functional genes found for three different plant ferritin subunits in the legume, Vigna unguiculata. AB - The iron storage protein, ferritin, in plants can occur in multiple molecular forms that, until now, were proposed to be derived from degradation of a single mature polypeptide subunit (2,7,17), which is assembled into the holoprotein and functions in plastids. We have carried out some definitive experiments with the diploid legume, Vigna unguiculata (cowpeas), which show that there are functioning genes for three different ferritin subunits in the developing leaves. Unique segments of mRNAs which code for subunits with substantially different mature sequences were detected by PCR. Separate genes for each subunit were found by showing that each gene contained a unique intron. Thus, multiple molecular forms of ferritin can arise through differential expression of a family of genes in plants. PMID- 8484788 TI - Strong promoter activity of human and rat islet amyloid polypeptide/amylin gene constructs in mouse beta cells (beta TC 3). AB - Islet amyloid polypeptide (IAPP)('amylin') is co-produced with insulin in pancreatic beta cells and is the formative polypeptide of pancreatic amyloid in patients with type 2 (non-insulin-dependent) diabetes mellitus. Islet amyloid and type 2 diabetes occur in man, but not in rat. To study transcription regulation of IAPP gene expression in man and rat, luciferase reporter constructs containing different portions of the upstream region of both IAPP genes were expressed in transfected cells. Both the human and the rat IAPP gene constructs revealed higher promoter activity in beta cells (particularly in beta TC3 cells) than in non-beta cells. In both IAPP genes potential transcription elements, with homology to insulin gene transcription elements, were identified. beta TC3 cells provide a good model system in which to study regulation of human and rat IAPP gene expression. PMID- 8484789 TI - The primary structure of rat ribosomal protein L36. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L36 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L36 has 104 amino acids, the NH2-terminal methionine is removed after translation of the mRNA and has a molecular weight of 12,128. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 8 to 11 copies of the L36 gene. The mRNA for the protein is about 500 nucleotides in length. Rat L36 is related to yeast ribosomal protein YL39. PMID- 8484790 TI - Mitochondrial Ca2+ uptake at submicromolar [Ca2+]i in permeabilised pancreatic acinar cells. AB - We studied the uptake of Ca2+ in different intracellular Ca2+ pools by use of steady-state measurement of 45Ca2+ in a preparation of digitonin-permeabilized pancreatic acinar cells. The Ca2+ content of all intracellular pools was assessed at different free Ca2+ concentrations between 0.1 and 1 microM. At low Ca2+ concentrations, almost 50% of Ca2+ was taken up, ATP-dependent, in a non mitochondrial pool. Even at 0.1 microM free Ca2+ the mitochondrial Ca2+ pool contained 26% (3.4 +/- 0.8 nmol Ca2+/mg prot) of the total Ca2+ and this percentage was increased to 49% at 1 microM Ca2+ (16.7 +/- 1.1 nmol Ca2+/mg prot). Our data also show that the uptake into the non-mitochondrial pool can be further differentiated on the basis of ATP-dependence, and that the ATP independent uptake has a biphasic dependency on the free Ca2+ concentration. PMID- 8484791 TI - Epidermal growth factor and isoproterenol stimulation of the Ras-guanine nucleotide exchange factor in proliferating rat parotid gland acinar cells. AB - Chronic treatment of rat parotid gland acinar cells with either epidermal growth factor (EGF) or the beta-adrenergic receptor agonist isoproterenol leads to cell proliferation through activation of the tyrosine kinase second messenger signalling pathway. Activation of p21ras activity in acinar cells was evaluated by measuring the levels of protein bound GTP and GDP. Both EGF and isoproterenol increased the amount of p21ras-GTP complex during active proliferation. The increase in bound GTP appears to be the result of an increased activity for the Ras-guanine nucleotide exchange factor. PMID- 8484792 TI - Interaction of dystrophin with cytoskeletal proteins: binding to talin and actin. AB - Dystrophin, the protein product of the Duchenne gene, is thought to be a member of muscle membrane cytoskeleton. In this work we studied the interactions of purified dystrophin from rabbit skeletal muscle sarcolemma membranes with other cytoskeletal proteins. The interaction of dystrophin with purified talin from chicken gizzard was tested by solid phase immunoassay. Under these conditions dystrophin bound talin with high affinity (Kd 3.5 nM). Vinculin purified from chicken gizzard did not bind dystrophin, but it inhibited the binding of dystrophin to talin. Furthermore, co-sedimentation and solid phase immunoassay experiments both demonstrated that native dystrophin binds purified actin from rabbit skeletal muscle. In conclusion, our results show that dystrophin can interact in vitro with proteins that are members of muscle membrane cytoskeleton. These proteins may represent additional sites for anchoring dystrophin to sarcolemma. PMID- 8484793 TI - Mutation of arginine 86 to proline in the insulin receptor alpha subunit causes lack of transport of the receptor to the plasma membrane, loss of binding affinity and a constitutively activated tyrosine kinase in transfected cells. AB - We have investigated the role of Ser 85 and Arg 86 of the human insulin receptor (HIR) in insulin binding and tyrosine kinase activity by mutational analysis. Four mutant cDNAs were created (R86P, R86N, S85T+R86N, S85W+R86K) and stably transfected into BHK cells. R86P-HIR was also transiently expressed in 293 cells. Only the R86P receptor had substantially altered properties: lack of transport to the plasma membrane, loss of insulin binding, a constitutively activated autophosphorylation and tyrosine kinase, and an incomplete processing. Some of these alterations mimic those reported for the insulin receptor of the leprechaun Atl, which has a homozygous R86P mutation (Longo, N., et al, Biochem. Biophys. Res. Commun., 167, 1229, 1990; Clin. Res., 40, 2, 329, 1992). PMID- 8484794 TI - Effect of sulfhydryl reagents on spectrin states on the erythrocyte membrane. AB - The unique properties of erythrocytes are largely determined by its fibrillar network under the plasma membrane. Spectrin, one major component of the membrane skeleton, has been suggested to play a central role in this process. To understand the mechanism underlying this process, the effect of the sulfhydryl groups of erythrocyte membrane on spectrin structure and function was studied. By using non-denaturing gel analysis, dithiothreitol was found to protect spectrin in its tetramer state. In contrast, iodoacetamide and N-ethylmaleimide enhanced conversion of the spectrin tetramer to dimer and decreased its binding to the membrane. Moreover, when the membrane was treated with cadmium, the tetramer was converted to the dimer on the membrane, while zinc had no effect. Hemolysis experiments showed that cadmium could lyse erythrocytes in vitro. These results indicated that preservation of the spectrin tetramer or even higher oligomer states, by the sulfhydryl groups may be important to the membrane integrity and the intact cell functions. PMID- 8484795 TI - Recombinant f1 phage particles can transfect monkey COS-7 cells by DEAE dextran method. AB - Recombinant f1 phage particles containing cDNA of the human urokinase type plasminogen activator (u-PA) under the control of the simian virus 40 (SV40) early promoter were used for transfection of monkey COS-7 cells using a DEAE dextran method. The fibrinolytic activity of u-PA was detected in the culture medium of the 10(5) cells transfected with the phage particles containing single stranded (ss) DNA of more than 0.2 ng. This finding will lead us to develop a simple and efficient method for expression cloning using mammalian cells. PMID- 8484796 TI - Facile cloning and sequence analysis of goose delta-crystallin gene based on polymerase chain reaction. AB - To facilitate the cloning of delta-crystallin gene, the product of which is a major lens protein present in the avian and reptilian lenses, polymerase chain reaction (PCR) was employed to amplify cDNAs constructed from the poly(A)+RNA of goose lenses. The PCR product was then subcloned into pUC19 vector and transformed in E. coli strain JM109. Plasmids purified from the positive clones were prepared for nucleotide sequencing by dideoxynucleotide chain-termination method. Sequencing several clones containing 1.4 kb DNA inserts encoding delta crystallin constructed a complete and unambiguous full-length reading frame of 1401 base pairs covering a deduced protein sequence of 465 amino acids excluding the universal translation-initiating methionine. The goose delta-crystallin shows 88, 94, 88 and 69% sequence identity to pigeon delta, duck delta 2, chicken delta 1 crystallins and human argininosuccinate lyase respectively. It is also shown that, similar to duck delta 2 and in contrast to pigeon delta crystallin, goose delta-crystallin appears to possess high argininosuccinate lyase activity despite the fact that a highly homologous structure is shared among these homologous proteins. Structural analysis and comparison of these closely related delta crystallin homologues with or without enzymatic activity should be of value in unraveling the intriguing evolutionary process leading to the development and evolution of active enzymatic crystallins in the lenses of certain avian species. PMID- 8484797 TI - Salen-manganese complexes are superoxide dismutase-mimics. AB - Complexes of manganese have previously been shown to exhibit SOD activity. In this study, we tested the ability of several (salen)-manganese complexes to scavenge O2.. Both neutral and cationic complexes were determined to be SOD mimics. The activity of the complexes was not affected by the presence of bovine serum albumin in the assay. For most compounds, the activity was inhibited by the addition of EDTA. The stability and high catalytic activity of some of these molecules suggest that they might have potential use in a variety of conditions which involve overproduction of oxygen free radicals. PMID- 8484798 TI - Catalytic properties and stability of a Pseudomonas sp.101 formate dehydrogenase mutants containing Cys-255-Ser and Cys-255-Met replacements. AB - Two mutants of bacterial formate dehydrogenase from Pseudomonas sp.101 (EC 1.2.1.2, FDH)-C255S (FDH-S) and C255M (FDH-M), were obtained and its properties were studied. Both mutations provided the high resistance to inactivation by Hg2+. Slow inactivation of mutants by DTNB reveals the presence in FDH molecule of another essential cysteine residue. Specific activities of FDH, FDH-S and FDH M were 16, 16 and 9.5 U/mg of protein, respectively. Km on formate was 7.5, 7.5 and 20 mM and Km on NAD(+)-0.1, 0.3 and 0.6 mM for FDH, FDH-S and FDH-M, respectively. Mutations of Cys255 on Ser or Met resulted in increasing of enzyme stability at 25 degrees C and decreasing of thermostability (above 45 degrees C). Data obtained show that Cys255 is unique residue for providing both enzyme thermostability and catalytically optimal binding of coenzyme. PMID- 8484799 TI - Maintenance and induction in co-cultured rat hepatocytes of components of the cytochrome P450-mediated mono-oxygenase. AB - Hepatocytes grown in culture rapidly lose many of the cytochromes P450 (CYP) responsible for metabolizing foreign compounds. Among the proteins most readily lost are members of the CYP2B subfamily. We have investigated, by RNase protection assays, the ability of rat hepatocytes, cultured conventionally or co cultured with rat liver epithelial cells, to maintain the expression of genes encoding members of the CYP2B subfamily, and the inducibility of this expression by phenobarbital. After 4 days of conventional hepatocyte culture CYP2B mRNAs were undetectable, but remained inducible by phenobarbital. In co-cultured hepatocytes the abundance of the mRNAs remained relatively constant from 4-14 days. After 7 days of co-culture the concentration of the mRNAs was increased 12 15-fold by phenobarbital. RNase protection assays with probes capable of distinguishing between CYP2B1 and 2B2 mRNAs demonstrated that the ratios of the abundance and inducibility of the two mRNAs were the same in co-culture as in vivo. Co-cultured hepatocytes also maintained the expression of genes coding for two other components of the cytochrome P450-mediated mono-oxygenase, namely cytochrome P450 reductase and cytochrome b5. PMID- 8484800 TI - Uptake of acetaminophen (paracetamol) by isolated rat liver cells. AB - The characteristics of the uptake of acetaminophen (N-acetyl-p-aminophenol or paracetamol, APAP) in incubations of isolated rat liver cells were consistent with diffusion of the drug being the predominant mechanism of APAP influx in these cells at concentrations above 0.5 mM. At lower substrate concentrations (below 0.5 mM) a saturable component was apparent. Both uptake processes could have a role in the control of the metabolism of APAP, because, at low concentrations, there was no intracellular accumulation of unconjugated drug, all the APAP entering the cell being converted to sulphate and glucuronide. After addition of drug, there was a lag phase of approximately 5 min before APAP glucuronide and APAP-sulphate appeared in the incubation medium; during this time both conjugates accumulated inside the cells. These results have implications for our understanding of the mechanisms of APAP transport, and indicate how these processes may affect the drug's overall metabolism. PMID- 8484801 TI - Structure-activity relationships of cysteine esters and their effects on thiol levels in rat lung in vitro. AB - Pretreatment with cysteine esters increases cysteine (CySH) levels in rat lung and protects against the lethal effects of inhaled perfluoroisobutene in vivo. There are marked differences in the duration of protection achieved with different cysteine esters. In this study we have compared the uptake and metabolism of CySH, N-acetyl cysteine (NAc), cysteine esters and cystine esters in vitro using rat lung and liver homogenates and lung slices. Liver homogenates metabolized CySH and cysteine esters faster than lung homogenates. The half life (T1/2) of CySH in lung was 58.8 +/- 17.3 min and in liver was 14.0 +/- 1.6 min (mean +/- SEM). T1/2 of the esters in lung ranged between 6.5 and 12.1 min and in liver between 1.9 and 5.3 min. Cysteine tertiary butyl ester, which does not protect in vivo, was not hydrolysed to CySH by lung or liver homogenates. All esters increased and prolonged intracellular CySH concentrations in lung slices to a much greater extent than CySH itself. NAc did not raise intracellular CySH above that of the controls and no NAc appeared within the slice. After CySH incubation intracellular CySH was 0.9 +/- 0.1 nmol/mg wet wt at 10 min whereas after incubation with the esters it ranged between 2.60 and 3.65 nmol/mg wet wt. Cysteine cyclohexyl ester prolonged the increase of CySH the longest and cysteine methyl ester the shortest. CySH levels with cysteine cyclohexyl ester were 2.74 +/- 0.15 and 4.13 +/- 0.37 nmol/mg wet wt at 10 and 60 min, respectively, whereas with cysteine methyl ester, CySH levels were 2.60 +/- 0.5 and 1.25 +/- 0.08 nmol/mg wet wt at similar times. Cystine esters increased intracellular concentrations of both cystine and CySH. CySH concentrations ranged between 2.92 and 3.19 nmol/mg wet wt and cystine between 1.39 and 1.47 nmol/mg wet wt at 60 min. The elevation and duration of CySH in lung slices is well correlated with the duration of protection against perfluoroisobutene achieved in vivo. PMID- 8484802 TI - Derivatives of cinnamic acid interact with the nucleotide binding site of mitochondrial aldehyde dehydrogenase. Effects on the dehydrogenase reaction and stimulation of esterase activity by nucleotides. AB - A wide variety of cinnamic acid derivatives are inhibitors of the low Km mitochondrial aldehyde dehydrogenase. Two of the most potent inhibitors are alpha cyano-3,4-dihydroxythiocinnamamide (Ki0.6 microM) and alpha-cyano-3,4,5 trihydroxycinnamonitrile (Ki2.6 microM). With propionaldehyde as substrate the inhibition by these compounds was competitive with respect to NAD+. alpha Fluorocinnamate was a much less effective inhibitor of the enzyme, with mixed behaviour towards NAD+, but with a major competitive component. These cinnamic acid derivatives were ineffective as inhibitors of the aldehyde dehydrogenase catalysed hydrolysis of p-nitrophenyl acetate, but inhibited the ability of NAD+ and NADH to activate this activity. Inhibition of the stimulation of esterase activity was competitive with respect to NAD+ and NADH, and the derived Ki values were the same as for inhibition of dehydrogenase activity. NAD+, but not acetaldehyde, could elute the low Km aldehyde dehydrogenase from alpha cyanocinnamate-Sepharose, to which the enzyme binds specifically (Poole RC and Halestrap AP, Biochem J 259: 105-110, 1989). The cinnamic acid derivatives have little effect on lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase or a high Km aldehyde dehydrogenase present in rat liver mitochondria. It is concluded that some cinnamic acid derivatives are potent inhibitors of the low Km aldehyde dehydrogenase, by competing with NAD+/NADH for binding to the enzyme. They are much less effective as inhibitors of other NAD(+)-dependent dehydrogenases. PMID- 8484803 TI - Contribution of 4-methylthio-2-oxobutanoate and its transaminase to the growth of methionine-dependent cells in culture. Effect of transaminase inhibitors. AB - The growth in culture of methionine-dependent transformed cells of human, rat and mouse origin was arrested in the absence of L-methionine (Met) but took place in the presence of 4-methylthio-2-oxobutanoic acid (MTOB), the keto acid of Met. From 24 hr after seeding, cells grew in 0.1 mM MTOB medium at a rate comparable to that in 0.1 mM Met medium. Using [35S]MTOB, it was found that the Met synthesized was used in normal MRC-5 cells and in transformed HeLa cells to the same extent for protein, adenosylmethionine and adenosylhomocysteine syntheses. However, when the free Met content was examined, it was found to be 3-fold greater in HeLa than in MRC-5 cells. To examine the importance of this free Met for the growth of transformed cells, the transaminase responsible for converting MTOB to Met was chosen as a target enzyme for the synthesis of compounds with potential inhibitory activity. Since this is a multisubstrate enzyme, reduced Schiff bases were prepared containing both pyridoxal or other aromatic groups, as one constituent, and L-Met or other amino-acids in the free acid or ester or amide form, as the other constituent. Only esters containing the pyridoxal moiety and Met or certain of its structural analogues exhibited good selective growth inhibitory activity in that there was little (20%) or no effect on the growth of normal MRC-5 and derm cells, respectively, while that of transformed HeLa, HEp-2 and L1210 cells was strongly inhibited (80%). This inhibition was accompanied by a concomitant decrease in the activity of the MTOB transaminase in both HeLa and MRC-5 cells treated with 3c the most potent inhibitor. However, using [35S]MTOB it was found that MTOB itself accumulated 48% in HeLa but only 12% in MRC-5 cells treated with 3c. On the contrary [35S]Met formed from [35S]MTOB increased 3.7 fold in MRC-5 inhibitor-treated cells showing 20% growth inhibition whereas it decreased 38% in HeLa-treated cells showing 80% growth inhibition. This decrease in cellular Met in HeLa is not responsible for growth arrest. Indeed the growth of HeLa cells could not be restored by adding a 10-fold excess of Met. Since MTOB can alleviate Met-dependence, the intracellular homeostasis of this metabolite may play a hitherto unsuspected role in controlling cell growth. PMID- 8484804 TI - Evidence that rat liver microsomal glutathione transferase is responsible for glutathione-dependent protection against lipid peroxidation. AB - Evidence that rat liver microsomal glutathione transferase is responsible for the glutathione-dependent inhibition of lipid peroxidation in liver microsomes has been obtained. Activation of the microsomal glutathione transferase in microsomes by cystamine renders this organelle even more resistant to lipid peroxidation in the presence of glutathione compared with untreated microsomes. Upon examining the effect of seven glutathione analogues on lipid peroxidation, it was found that only those that serve as good substrates for the microsomal glutathione transferase (Glutaryl-L-Cys-Gly and alpha-L-Glu-L-Cys-Gly) can inhibit lipid peroxidation. The lack of inhibition by the other five analogues (alpha-D-Glu-L Cys-Gly, gamma-D-Glu-L-Cys-Gly, beta-L-Asp-L-Cys-Gly, alpha-L-Asp-L-Cys-Gly and alpha-D-Asp-L-Cys-Gly) shows the specificity of the protection and rules out any non-enzymic component. Inhibitors of selenium-dependent glutathione peroxidase (mercaptosuccinate at 50 microM) and phospholipid hydroperoxide glutathione peroxidase (iodoacetate, 1 mM + glutathione, 0.5 mM) do not inhibit the glutathione-dependent protection of rat liver microsomes against lipid peroxidation. Purified microsomal glutathione transferase, NADPH-cytochrome P450 reductase and cytochrome P450 were reconstituted in microsomal phospholipid vesicles by cholate dialysis. The resulting membranes contained functional enzymes and did display enzymic lipid peroxidation induced by 75 microM NADPH and 10 microM Fe-EDTA (2:1). This model system was used to investigate whether microsomal glutathione transferase could inhibit lipid peroxidation in a glutathione-dependent manner. The results show that 5 mM glutathione did inhibit lipid peroxidation when functional microsomal glutathione transferase was included. This was not the case when the enzyme had been pre-inactivated with diethylpyrocarbonate. Furthermore, the protective effect of glutathione could be partly reversed by an inhibitor (100 microM bromosulphophtalein) of the enzyme. Apparently, rat liver microsomal glutathione transferase has the capacity to inhibit lipid peroxidation in a reconstituted system. PMID- 8484805 TI - An unusual profile of musk xylene-induced drug-metabolizing enzymes in rat liver. AB - We have demonstrated previously that musk xylene, a non-mutagenic carcinogen, is a novel and specific inducer of CYP1A2 in rats (Iwata et al., Biochem Biophys Res Commun 184: 149-153, 1992). In the present study, the effects of musk xylene (50, 100 or 200 mg/kg body weight, i.p., for 5 consecutive days) on both Phase I and Phase II metabolizing enzymes in rat liver were investigated further and more completely. Among the mixed-function oxidases monitored, 7-ethoxycoumarin deethylase and 7-pentoxyresorufin depentylase activities were increased at all dose levels from 1.6- to 1.7-fold and 2.6- to 3.1-fold, respectively. Benzo[a]pyrene hydroxylase activity was increased significantly at only the 200 mg/kg dose level of musk xylene (1.5-fold). Regarding Phase II enzymes, activities of both cytosolic DT-diaphorase and glutathione S-transferase (GST) were increased up to 2.0- to 2.4-fold by musk xylene in a dose-dependent manner. Western blot analysis revealed that the changes in these activities were caused by increases in the amounts of DT-diaphorase and GST Ya subunit. Microsomal UDP glucoronyltransferase (UDPGT) activity assayed with p-nitrophenol as substrate was increased 1.6- to 2.0-fold. These results show that musk xylene induces both Phase I cytochrome P450 mixed-function oxidase (CYP1A2 specific) and Phase II metabolizing enzyme systems (DT-diaphorase, GST Ya subunit and UDPGT) in rat liver. PMID- 8484806 TI - Early response gene induction following DNA damage in astrocytoma cell lines. AB - Early response genes (ERGs) are a group of genes with low or absent expression in quiescent cells that can be induced rapidly by a variety of proliferation and differentiation stimuli. c-jun and c-fos are prototypes for this group of genes. Recent evidence suggests that DNA damaging agents such as cytotoxic drugs and ionizing radiation can elicit strong ERG induction, suggesting that these genes may be involved in DNA damage repair and/or cell death. Paralleling this interest in drug-induced ERG expression is a growing body of evidence implicating ERG expression as important to the intrinsic function of the central nervous system. We therefore set out to explore the pattern of chemotherapeutic drug- and radiation-induced c-jun and c-fos expression in neuroectodermally (astrocytic) derived cell lines. We have demonstrated that various chemotherapeutic agents and ionizing radiation can induce c-jun in a time- and concentration-dependent manner. Furthermore, this induction can be prevented by pretreatment of the cells with agents that protect against DNA damage. Finally, we have demonstrated that c fos and c-jun expression and induction are discoordinately regulated, reflecting a difference in astrocytic cell lines compared to hematopoietic cell lines. The possible relevance of these observations to the clinical resistance of astrocytic tumors to standard chemotherapy and radiation is discussed. PMID- 8484807 TI - Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes. AB - The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide. Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes. Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes. Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates. Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies. Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s. These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients. PMID- 8484808 TI - Interindividual variability of carbonyl reductase levels in human livers. AB - Interindividual variability of carbonyl reductase levels in human livers (N = 11) was examined by measuring reductase activity toward various substrates and by western blot analysis using anti-rat ovarian carbonyl reductase CR2 antibody. The carbonyl reductase activity toward p-nitrobenzaldehyde (PNBA) (58.1 +/- 5.4 nmol/mg protein/min, mean +/- SE) was highest among the substrates examined, followed by 4-benzoylpyridine (4BP) (14.4 +/- 2.0 nmol/mg protein/min) and p nitroacetophenone (PNAP) (2.00 +/- 0.37 nmol/mg protein/min). The reductase activity (6.33 +/- 0.56 pmol/mg protein/min) toward 13,14-dihydro-15-keto prostaglandin F2 alpha (15KD-PGF2 alpha), which is a diagnostic substrate for rat ovarian carbonyl reductases, was relatively high compared to that in other species. Western blot analysis revealed that each human liver contained several immunoreactive proteins to anti-CR2 antibody. The activities toward 15KD-PGF2 alpha (r = 0.85, P < 0.01) and 4BP (r = 0.84, P < 0.01), but not PNBA (r = 0.53, not significant) or PNAP (r = 0.52, not significant), were closely correlated with the relative amounts of the high molecular weight immunoreactive proteins determined with a densitometer. Thus, the major carbonyl reductases in human liver are similar to those of rat ovarian enzymes. PMID- 8484809 TI - New procedure for analysing drug binding data, exemplified by warfarin binding to human serum albumin. AB - Determination of binding constants for multiple binding of a ligand usually results in highly variable figures. We have found that the variations depend mainly upon cooperativity of ligand binding, and that cooperativity is generally absent on binding to human serum albumin. When this is taken into account it becomes possible to obtain binding constants with only slight variation. A computerized curve fitting procedure for analysing binding data has been established consisting of the following steps. (1) Fitting of Scatchard's equation to observed binding equilibrium data to obtain a best-fit set of Scatchard binding constants. (2) Repetition of the fitting procedure, not to obtain a best fit but to generate 30 acceptable sets of Scatchard binding constants. (3) Fitting of Adair's equation to the observed points to obtain a best fit. If the sum of weighted and squared deviations is significantly smaller than the fitting of Scatchard's equation, cooperativity should be considered. If not, cooperativity cannot be demonstrated and the binding constants obtained by fitting Scatchard's equation can be accepted, with the variations found. (4) Final transformation of all Scatchard constants to Adair's. To illustrate the method warfarin data obtained by equilibrium dialysis was used. PMID- 8484810 TI - Lipid peroxidation in rat liver microsomes during naproxen metabolism. AB - Naproxen, a non-steroidal anti-inflammatory drug, is known to be highly effective and relatively safe, but some side-effects in the liver have been reported. In the present study, the effect of naproxen metabolism on rat liver microsomes was studied by determining lipid peroxidation in terms of thiobarbituric acid reactive substances (TBA-RS), high molecular weight protein aggregates and fluorescent substances formed in the microsomal suspension containing naproxen, NADPH and MgCl2. Lipid peroxidation was found to occur at 10 mM naproxen. Production of chemiluminescence from the microsomal suspension was observed during naproxen metabolism. The time course of 6-demethyl-naproxen formation by O demethylation of naproxen appeared to be comparable to that of the chemiluminescence production in their initial periods of production. These results suggest that the lipid peroxidation was provoked through the reactive oxygen species generated during the oxidative metabolism of naproxen. PMID- 8484811 TI - [Conformation of fragment 66-72 of interleukin-2 complexed with a monoclonal antibody to interleukin-2]. AB - 1H-NMR spectra of the interleukin-2 synthetic fragment Ac-Leu66-Glu-Glu-Val-Leu Asn-Leu72-OCH3 in the presence or absence of the monoclonal antibody were analysed. The data obtained are consistent with an extended unordered conformation of the free peptide. Measurements of NOESY cross-peak intensities allowed us to determine the spatial structure of the peptide bound to the antibody. The peptide has an amphiphilic surface with hydrophobic and hydrophilic amino acid side chains clustered on the opposite sides of its alpha-helical-like structure. The hydrophobic and hydrophilic clusters are located on the opposite sides of the bound peptide's surface. The hydrophobic side chains contact the antibody surface, while the hydrophilic ones are oriented into the solvent (T. A. Balashova et al. (1991) Bioorgan. Khim. (USSR), v. 17, p. 1470-1486). Hydrolysis of the methyl ester slowly ocurs in the presence of the antibody. This process does not alter the conformation of the peptide bounded with the antibody, though decreases the peptide's affinity to the antibody. PMID- 8484812 TI - [X-ray structural study of the crystalline structure of human progastricsin by a molecular replacement method]. AB - The human progastricsin crystal structure has been solved by the molecular replacement method. The intensities of reflections from native progastricsin crystals were measured at the 4.0 A resolution by the omega-scan method with a Nicolet P3 diffractometer operated in automatic regime. To determine the orientation and position of progastricsin molecules in the unit cell, programme packages MERLOT and BRUTE were applied running on a MicroVAX-II computer. Prior to the translation search, several rotation function peaks were subjected to a rigid body refinement against the correlation coefficient between the observed and calculated structure factors. This approach clearly identified the correct orientation of the molecule. The solution obtained from the BRUTE translation function map was refined by the 6-dimensional correlation search and then by programme CORELS. The human progastricsin molecules packing in the crystal unit ell is described. PMID- 8484813 TI - [Synthesis and biological properties of new analogs of delta-sleep peptide. I. Antiepileptic effect]. AB - To study structure-functional relationship in the series of DSIP, eleven DSIP analogues varying in positions 1, 2 and 6 were synthesized by the solid-phase method using both Boc- and Fmoc-approaches. The antiepileptic action of these analogues was compared with that of DSIP. The seizure activity was induced by the corazol or picrotoxin i. p. injection. Some analogues proved more efficient as antiepileptic agents than DSIP after their central (50 micrograms/kg in rats) and peripheral (1.0 mg/kg in mice) administration. PMID- 8484814 TI - [2D-1H-NMR-study of the conformation of transmembrane segments of C, E, and G bacteriorhodopsin]. AB - Conformations of synthetic peptides, analogues of the membrane spanning segments C (residues 67-106), E (128-162) and G (190-233) of bacteriorhodopsin Halobacterium halobium were studied by two-dimensional 1H-NMR spectroscopy. Peptides were solubilized in the mixture chloroform-methanol (1:1), 0.1 M LiC1O4. The spectrum resonances were assigned by means of phase-sensitive DQF-COSY, TOCSY and NOESY techniques. Interproton nuclear Overhauser effects were derived from NOESY spectra. Amide protons with slow deuterium exchange rates were determined. Analysis of the obtained data showed that segments C, E and G form right-handed alpha-helices including residues 77-101, 131-159 and 198-227, respectively. PMID- 8484815 TI - [Solid-phase synthesis of peptides modelling the transmembrane segment of bacteriorhodopsin]. AB - Peptides modelling transmembrane segments C, D, E and G of bacteriorhodopsin were obtained by solid phase method using the conventional Boc strategy. Protected peptides were assembled on PAM polystyrene support. Side chain protecting groups were: Tos for Arg, Bzl for Thr and Ser, cHx for Asp and Glu, Bzl(Cl2) for Tyr, For for Trp, Z(Cl) for Lys. Syntheses were performed on a modernized Beckman 990 synthesizer in the automatic mode. Double couplings by a preformed hydroxybenzotriazole ester were used for all residues. Qualitative and quantitative ninhydrine tests were used to monitor coupling efficiency. Removal of protecting groups and peptide cleavage were achieved by hydrogen fluoride, containing p-cresol and p-thiocresol as scavengers. Preparative reverse phase HPLC was used for purification. Peptide structure and homogeneity were confirmed by amino acid analysis, 1H-NMR and analytical HPLC. PMID- 8484816 TI - [Cloning the Staphylococcus aureus enterotoxin B gene, obtained by polymerase chain reaction, and its expression in Escherichia coli cells]. AB - To determine the Staphylococcus aureus enterotoxigenicity, we have developed an approach based on polymerase chain reaction (PCR). Using this method several S. aureus strains have been screened for the presence of the enterotoxin B gene. A DNA fragment of the selected strain (FRI 722H) containing enterotoxin B gene has been obtained by the PCR method and cloned in the pUC19 vector. It is shown that enterotoxin B with the leader peptide forms insoluble complexes in E. coli cells, whereas the mature toxin is present in cytoplasmic fraction in a soluble form. The recombinant toxin made up for 1.7% of the total cellular protein in E. coli JM 109 cells. PMID- 8484818 TI - 1993 Regional Meetings of the American College of Rheumatology. Abstracts. PMID- 8484817 TI - [Synthesis of oligodeoxyribothymidylate derivatives containing alkylating groups and residues of biotin, for directed modification of chromatin]. AB - An oligodeoxythymidylate derivative bearing an alkylating group at the 5'-end and biotin at the 3'-end (RCl-(pdT)16-bio) was synthesized. This reagent alkylates polyA-tracts of DNA in HeLa nuclei specifically via complementary complexes with single-stranded segments of DNA and by the preliminary treatment of chromatin with S1-nuclease, since the reaction is inhibited by an excess of the corresponding free oligothymidylate. The reagent will be used to study the distribution of local unwinded parts of polyA-repeats of DNA in human chromatin by the electron microscopy. PMID- 8484819 TI - Practitioners speak out. AB - Most of our colleagues report that the recession has caused them to alter the way they have been providing services on a day-to-day basis. Even though changes, cutbacks, and concessions have been made, our professions have, for the most part, been resilient and have been spared the massive layoffs and salary cuts seen in other sectors of the workforce. In fact, given our colleagues' comments, our professions seem to have fared well in what have been gloomy times for many other industries and careers. The number of vacant positions far exceeded the number of people seeking positions at the 1992 ASHA convention (many report position vacancies that have gone unfilled for some time); salaries appear to be keeping up with or in some cases even exceeding inflation; and the number of clients who need us keeps growing. No one knows what lies ahead. We do know that our professions survived the recession. In the years ahead we will be preparing the groundwork for the practice of the professions in the next century. It will be a time of change in the delivery of care. We will be required to be as creative or even more creative than we have been. PMID- 8484820 TI - Consumers speak out. PMID- 8484821 TI - ASHA speaks out. PMID- 8484822 TI - The state of infant hearing impairment identification programs. PMID- 8484823 TI - Ethics education in speech-language pathology and audiology training programs. PMID- 8484824 TI - Gender-related issues. PMID- 8484825 TI - Medications alert. PMID- 8484826 TI - Marketing for Native Americans needed. PMID- 8484827 TI - Identification in the chicken of GRL1 and GRL2: two granule proteins expressed on the surface of activated leukocytes. AB - We report the production of two monoclonal antibodies reacting, respectively, with a 92-kDa protein (GRL1) and a 40- to 65-kDa membrane glycoprotein (GRL2), both present in chicken thrombocyte and myelocyte granules. We examined the expression of GRL1 and GRL2 during the development of the hematopoietic system: GRL1 is restricted to thrombocytes and myelocytes, whereas GRL2 is present in thrombocytes, myelocytes, myeloid progenitors, and a subpopulation of erythroid progenitors. In the lymphoid lineages, neither GRL1 nor GRL2 is expressed during thymus and bursa ontogeny or on resting peripheral blood lymphocytes. However, CD3+ T lymphoblasts obtained by mitogenic stimulation of GRL2-negative quiescent T lymphocytes are stained on their surface by anti-GRL2 Mab. In vitro stimulation of thrombocytes and granulocytes with their specific secretagogues results in the expression of GRL1 and in the overexpression of GRL2 on the cell surface. These observations are consistent with the following two conclusions: the presence on the cell surface of GRL1 epitope is a marker of thrombocyte and myelocyte activation; GRL2 epitope is present on the granule membrane of leukocytes, including T cells. In that respect, GRL2 appears to share certain features with leukocyte activation antigens recently described in human. PMID- 8484828 TI - Aural neoplasms. PMID- 8484829 TI - Prognostic significance of progression of coronary atherosclerosis. AB - BACKGROUND: Angiographic progression of coronary atherosclerosis is frequently observed in clinical practice and is used as an end point in clinical trials; however, its prognostic significance is unclear. METHODS AND RESULTS: Progression defined as an increase in diameter stenosis by > or = 15% of at least one coronary lesion was seen in 141 (42%) of 335 patients who underwent repeat coronary arteriography after a 2-year interval as part of clinical trial. Coronary lesions were measured quantitatively from comparable end-diastolic frames selected by a radiologist viewing each pair of films together. During a mean follow-up of 44 +/- 10 months after the second arteriogram, cardiac death occurred in 19 patients (5.7%), cardiac death or nonfatal infarction was seen in 40 cases (11.9%), and 90 patients (26.9%) underwent coronary revascularization. At least one end point event occurred in 112 of the 335 patients. Sixteen of the 19 cardiac deaths were in progressors, a relative risk of 7.3 (95% CI, 2.2-24.7; p < 0.001). The relative risk of cardiac death or nonfatal infarction for progressors was 2.3 (1.3-4.2, p = 0.009) and of any cardiac event was 1.7 (1.3 2.3, p < 0.001). A stepwise multivariable Cox regression model of time to event was used to assess the relative contribution of progression as a predictor of coronary events. Low ejection fraction (p = 0.001), progression (p = 0.001), and hypertension (p = 0.011) were retained as predictors of cardiac death. Angina and the number of diseased vessels were the strongest predictors of revascularization. CONCLUSIONS: Coronary progression is a strong, independent predictor of future coronary events, particularly cardiac death, and its use as a surrogate end point in clinical trials is justified. PMID- 8484830 TI - Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease. AB - BACKGROUND: An association of chronic Chlamydia pneumoniae infection to coronary heart disease has been suggested recently. In a recent study, we demonstrated circulating immune complexes containing chlamydial genus-specific lipopolysaccharide in patients with coronary heart disease. The objective of the present study was to investigate whether C. pneumoniae species-specific immune complexes are present in chronic coronary heart disease. METHODS AND RESULTS: The presence of Chlamydia-specific circulating immune complexes was studied in 46 patients with chronic coronary heart disease and in control subjects. Chlamydial lipopolysaccharide-containing immune complexes were detected with the antigen specific capture method, and they were present in 41% of patients and 15% of control subjects (p < 0.01). The presence of C. pneumoniae antibodies in circulating immune complexes was studied by testing the specificity of antibodies derived from isolated and dissociated immune complexes by microimmunofluorescence testing and immunoblotting. The C. pneumoniae indexes based on the relative amount of immune complex-derived antibodies and free antibodies were significantly higher among patients compared with control subjects (median, 1/8 versus 1/16; p < 0.001). Immune complex bound antibodies showed specificity for 98-kd and 42-kd proteins of C. pneumoniae. CONCLUSIONS: The results suggest that the majority of the patients with chronic coronary heart disease have a chronic C. pneumoniae infection in which chlamydial components have an easy access to circulation to form immune complexes with preexisting antibodies. These findings give further evidence for the association of chronic C. pneumoniae infection with coronary heart disease. PMID- 8484831 TI - Chlamydia in atherosclerosis. PMID- 8484832 TI - The development and evaluation of a sexual harassment contact person training package. AB - The effectiveness of a training package to teach listening and helping skills to three pairs of sexual harrassment contact person trainees was evaluated, using a multiple probe design. The training package comprised five components: behavioral specifications, rationales, situational examples, study guides, and role-play exercises, provided in a written instructional format based on guidelines developed by Fawcett and Fletcher. Evaluation involved pre- and posttraining measures of target behavior occurrence, relevant knowledge, and self-rated confidence level. Ratings of performance were also provided by potential consumers as a measure of social validity. Findings indicated that the package was effective in increasing listening and helping skills, knowledge, and confidence of trainees and that skills generalized to new simulated cases and were maintained over time. PMID- 8484833 TI - Financial impact of the Medicare Fee Schedule on a large multispecialty faculty practice in an academic medical center. AB - Although there have been preliminary studies of the financial impact of the Medicare Fee Schedule (MFS) on specialty-specific groups of practicing physicians in an academic setting, there has been no published report of the financial impact of the MFS on an entire multispecialty academic faculty practice. This 1992 study reports the estimated financial impact of the MFS on the faculty practice at the University of Michigan Medical School (UMMS). The authors calculated the difference between the Medicare payments to be received when the MFS is completely implemented in 1996 and the payments received in 1991, and then repeated this process for each year of the transition period, 1992-1996. The UMMS will experience a $1.2 million (-4.7%) loss under the fully implemented MFS. The medical departments project an 8% gain, while substantial losses are projected for the surgical departments (-10%) and hospital-based departments (-15%). Projections indicate that obstetrics-gynecology and ophthalmology will lose nearly 20% and that surgery will lose 9%. But large percentage gains are projected for neurology (+43%), physical medicine (+25%), and family practice (+17%). Analysis of the MFS transition's effects shows an abrupt and unpredictable financial impact in the first year. Faculty practice plans may be more disadvantaged under the MFS than other physician groups, yet the uncertain impact of the MFS in the first year (1992) may inhibit accurate financial planning for all physician groups. PMID- 8484834 TI - Attitudes toward the medical career: findings from the Alpha Omega Alpha survey of college and university undergraduates. AB - In 1989, when the number of applicants to medical schools had been comparatively low for several years, trustees of Alpha Omega Alpha commissioned Louis Harris and Associates to conduct a survey to investigate the attitudes that led college undergraduates toward or away from choosing medical careers. A total of 1,780 college students and 93 premedical advisors from 100 U.S. schools were interviewed in early 1990. The students were in three groups: a national cross section of 1,003 undergraduates who were not applicants to medical school; 500 medical school applicants for the entering class of 1990; and 277 students who had taken the Medical College Admission Test (MCAT), were qualified for admission, but had not applied. The authors acknowledge that the reasons that the medical school applicant pool was so low in the late 1980s and has fluctuated so widely in the last two decades are only partly understood. The data gathered indicate that job satisfaction was an extremely important factor in career choice for high percentages of students in all the groups surveyed; that 77% of all the students had never seriously considered applying to medical school; and that 70% saw no attraction in becoming a physician. Data on other problems that many of the students saw in medical education and the practice of medicine are reviewed, the role of premedical advisors is examined, and the advisors' views on what makes a promising applicant are described. Regarding the students who took the MCAT exam but did not apply to medical school, 81% indicated that they eventually planned to or were likely to apply.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8484835 TI - "Academic" CME and the social contract. AB - The term academic continuing medical education (CME) is defined and explored from the perspective of forces that have made its usage necessary. These forces include the new understandings of the place, impact, and scope of CME, and, in particular, the increasing entrepreneurial interests in the field, unrelated to the improvement of physicians' competence or performance, or to health care outcomes. In addition to principles of CME provision promulgated by the Accreditation Council of CME, and those of ethical CME providers, academic CME implies the critical appraisal of the providers' activities, the creation of new knowledge about how physicians learn and change, and the dissemination of information based on such knowledge. Finally, the nature of academic CME providers is discussed, and the potential role of CME in fostering the social contract between the medical professional and society is explored. PMID- 8484836 TI - Centralized decision making in management of the curriculum at the University of Michigan Medical School. PMID- 8484837 TI - Community-oriented medical education in Vellore, India. PMID- 8484838 TI - Curbing Congress' appetite for pork. PMID- 8484839 TI - Understanding and eradicating bias against women in medicine. PMID- 8484840 TI - Why don't more women choose surgery as a career? PMID- 8484841 TI - Broader implications of new CME guidelines for commercial support. PMID- 8484842 TI - Shared training experiences between health professionals. PMID- 8484843 TI - Clinical teaching by voluntary faculty. PMID- 8484844 TI - Teaching of medical students by neurology and neurosurgery faculty. PMID- 8484845 TI - Women physicians and their spouses. PMID- 8484846 TI - Freshman students' attitudes toward homosexuality. PMID- 8484847 TI - A health science center's pre-matriculation retreat. PMID- 8484848 TI - An information card on exposure to infectious body fluids. PMID- 8484849 TI - Mental health services for medical students: perceptions of students, student affairs deans, and mental health providers. AB - PURPOSE: To examine (1) whether there is any consistency among medical schools in mental health services provided and (2) how these services are perceived by student affairs deans, mental health service providers, and the students themselves. METHOD: Questionnaires were sent in October 1991 to the student affairs dean (or director), the individual responsible for student mental health services, and a student representative in each of the 126 U.S. and Canadian medical schools. Data were sought regarding personnel, individuals served, location, hours, administration, funding, confidentiality, administrative referrals, and respondents' suggestions for improvement. Possible differences among the three groups of respondents were tested by chi-square. RESULTS: Responses were received from 75 student affairs deans, 53 mental health providers, and 30 students. There was much diversity among schools in services provided, especially in the areas of administration and funding. Although perceptions of the three respondent groups were often the same, they differed significantly in a number of areas. Suggestions for improvement of services involved funding, personnel, hours, confidentiality and privacy, specialty services, preventive and support programs, and visibility. The suggestion most frequently made by the students was for increased information and visibility. CONCLUSION: The differences among schools coupled with the differing perceptions within schools indicate a need for a comprehensive consideration of what kinds of mental health services are needed and how they can best be made accessible to a diverse body of students experiencing a variety of academic and personal challenges. PMID- 8484850 TI - The triple-jump examination as an assessment tool in the problem-based medical curriculum at the University of Hawaii. AB - BACKGROUND: The three-step triple jump (TJ) examination aims to assess students' clinical problem-solving processes predominantly by means of subjective assessments administered by faculty. But training TJ administrators to ensure interrater reliability is both time- and cost-intensive, and difficult at best- hence the desire to test a more objective system of scoring students' TJ performances. METHOD: The sample was the 58 first-year students of the class of 1995, who in March 1992 were finishing the second 13-week unit in the problem based curriculum at the University of Hawaii John A. Burns School of Medicine. To determine how well the school had succeeded in standardizing and objectifying its TJ examination (used for all units in the first two years), scores were correlated for various objective examinations independent of the TJ, the TJ administrators' subjective assessments, and the TJ objective assessments (regarding number of problem-based hypotheses generated and number of hypothesis testing clinical database items elicited). The statistical methods used were linear regression, Student's unpaired t-test, chi-square, and the z-test. RESULTS: The TJ scores and independent objective examinations did not correlate significantly (suggesting that they assess different aspects of student achievement), but the TJ subjective and objective scores did correlate significantly. There were large standard deviations on the TJ objective scores, largely because one problem was significantly more difficult than the others (each student works on only one of several problems). However, the administrators' subjective scores for all problems were comparable. CONCLUSION: Because problems vary in difficulty, objective scores cannot be used across problems as a major component of all students' grades; but when a student has received an unsatisfactory score, an external reviewer can evaluate the appropriateness of the subjective score by comparing the student's objective performance with those of students who had the same problem and received higher subjective scores. That the administrators' subjective assessments for all problems were comparable not only suggests that the administrators were able to adjust for problem variability but also reinforces the appropriateness of using subjective assessments for the TJ examination. PMID- 8484851 TI - Senior medical students' knowledge of universal precautions. AB - BACKGROUND: Few data exist concerning the assessment of medical students' knowledge of universal precautions. The purpose of this study was to assess what students know--immediately before they graduate--about universal-precautions procedures. METHOD: The 151 fourth-year students of the class of 1992 at the University of Washington School of Medicine were given a questionnaire one week before graduation. They were asked to indicate the protective equipment required to safely complete ten common clinical procedures. For each procedure, the proportion of students who correctly indicated the protective equipment was calculated. RESULTS: The questionnaires were completed by 137 (91%) of the students. The mean percentage of correct answers by the responding students was 67%. For five of the ten procedures, from 104 to 123 (76-90%) of the students reported the proper levels of protection. For the remaining five procedures, from 58 to 75 (42-55%) of the students knew the proper levels of protection. CONCLUSION: The results of the survey are worrisome, because many students- immediately before they graduated--lacked adequate knowledge of universal precautions regarding the ten common clinical procedures. More emphasis on universal precautions during undergraduate medical education is needed. PMID- 8484852 TI - A training program in universal precautions for second-year medical students. AB - BACKGROUND: A training program in universal precautions was developed and implemented in 1991-92 for second-year students at the George Washington University School of Medicine and Health Sciences. The students were required to participate in a three-hour session that consisted of lecture, demonstration, and practice components focused on the risks of bloodborne-disease exposure and the techniques of phlebotomy and intravenous insertion using universal precautions. METHOD: All 135 second-year students participated in the lecture component, but only 120 students, who were unfamiliar with the procedures, were required to participate in the demonstration and practice components. Each of these students was asked to answer pre- and postsession knowledge questions and to rate his or her preparedness on a five-point Likert scale, ranging from 1, "not prepared at all," to 5, "well prepared." Paired t-tests were used to compare the pre- and postsession knowledge scores and self-assessed preparedness scores. At the end of the training program, the students were offered the opportunity to volunteer for additional, individualized training with the hospital phlebotomy service. Unpaired t-tests were used to compare differences between the postsession knowledge scores of the volunteers and nonvolunteers. RESULTS: A total of 103 students completed both pre- and posttests. The students' knowledge scores increased from means of 64.7% to 88.5% (p = .001). Their self-assessed preparedness scores also increased, ranging from a low of means of 1.6 presession and 3.4 postsession for intravenous insertion to a high of means of 3.19 presession and 4.26 postsession for addressing personal concerns about possible exposure. The 43 students who volunteered for additional training scored significantly better on the postsession knowledge questions than did the nonvolunteers, suggesting that those who may have needed it most failed to sign up for additional training. CONCLUSION: The training session significantly improved the students' knowledge and sense of their own competency. PMID- 8484853 TI - Changes in students' attitudes toward HIV-infected patients as the students progress through medical school. AB - PURPOSE: To examine how medical students' attitudes and intentions toward the treatment of persons infected with human immunodeficiency virus (HIV) changed as the students progressed through medical school. METHOD: Similar 44-item self administered questionnaires, to be completed anonymously, were given to 394 medical students at the University of Michigan Medical School in February 1989, when the students were in their first or second years, and to 378 of the same students in February 1991, when they were in their third or fourth years. Seven subscale variables were created, and their effects on students' willingness to treat HIV-infected patients were assessed. Bivariate statistics and logistic regression were used to relate the dependent and independent variables. RESULTS: In 1989, 201 (51%) of the students responded; in 1991, 208 (55%) responded. The students showed a high--but declining--degree of willingness to care for patients infected with HIV or at high risk of infection. Homophobic attitudes decreased, but so did the students' intentions to follow infection-control guidelines. The students who expressed a career interest in surgery specialties indicated less willingness to provide care for HIV-infected patients, presumably because these students felt that they would be at a higher risk of exposure. CONCLUSION: Overall, the students' responses indicated that over the two years of the study they became more restrictive in their attitudes toward HIV-positive patients, felt less personal obligation toward caring for these patients, and were less likely to use appropriate infection-control methods to ensure their own safety. PMID- 8484854 TI - Hospital-based versus community-based clinical education: comparing performances and course evaluations by students in their second-year pediatrics rotation. AB - BACKGROUND: Increasing use of outpatient settings for clinical education raises the question of their effectiveness compared with that of inpatient settings. METHOD: At the University of Minnesota Medical School-Minneapolis in 1987-88, the 190 second-year students participated in a six-week tutorial rotation introducing them to clinical pediatrics: 52 (27%) were in hospital settings and 138 (73%) were in community outpatient settings. Almost all the students (178) evaluated their rotations by responding to both structured and open-ended questions, using a Likert scale for the structured questions. At the completion of the second year, all 190 students took an objective structured clinical examination (OSCE) that included five pediatrics stations. Student's t-test was used to compare (1) the mean ratings the hospital-based and community-based students gave their pediatrics rotations and (2) the mean scores earned by the two groups of students on the five pediatrics stations in the OSCE. RESULTS: There were no statistically significant differences between (1) the two groups' mean ratings of the clinical experience overall or of the quality of teaching or (2) the groups' mean scores on any of the OSCE stations. CONCLUSION: That the hospital-based and community based students performed comparably on the OSCE and gave similar evaluations of their pediatrics rotations supports the use of community practitioners to provide students with their initial clinical training. Moreover, community-based teaching sites replicate situations in which most students will eventually practice medicine. PMID- 8484855 TI - Teaching medical ethics to first-year students by using film discussion to develop their moral reasoning. AB - PURPOSE: To evaluate a project on teaching medical ethics to first-year students by using film discussion to develop the students' moral reasoning. METHOD: The participants were 114 first-year students at Texas A&M University Health Science Center College of Medicine in 1989-90, 1990-91, and 1991-92: (1) 48 (20 women and 28 men) who participated during the fall quarter in an elective course on social issues in medicine, which consisted of weekly one-hour discussions of short films; (2) 37 (18 women and 19 men) who participated in the course during both the fall and winter quarters; and (3) a control group of 29 (8 women and 21 men) who did not take the course and so had no exposure to the film discussions. The influence of the discussions on the students' moral reasoning was measured by using Rest's Defining Issues Test for pretests and posttests. The scores of the three groups were compared by using multivariate analysis of variance. RESULTS: There were statistically significant increases in the moral reasoning scores of both the course registrants with one-quarter exposure to the film discussions (p < .002) and those with two-quarter exposure (p < .008) compared with the scores of the students who did not take the course and had no exposure (p < .109). CONCLUSION: No doubt there was a self-selecting bias on the part of the course registrants; however, since both groups of registrants showed significant increases on their posttest scores, clearly the course did have a positive influence on these students' moral reasoning. Thus, it is possible to develop young people's moral reasoning in medical school as well as in earlier educational environments. PMID- 8484856 TI - Extent to which guided-discovery teaching strategies were used by 20 preceptors in family medicine. AB - BACKGROUND: Learners learn more and are able to categorize problems at higher levels when their teachers use guided-discovery strategies (e.g., questions and advice to investigate relationships between concepts), as opposed to directly telling learners the answers. This study examines the extent to which clinician preceptors of residents use guided-discovery strategies when faced with a diagnostic problem-solving situation. METHOD: Twenty family medicine preceptors from four residencies volunteered in 1991-92 to role-play with a simulated first year resident on a single standardized case. Judges coded the preceptors' verbal behaviors by type (question, statement, or advice) and by category. The categories were teacher, i.e., behaviors relating to more than the present case (hence exemplifying guided-discovery strategies), and consultant, i.e., behaviors relating to the successful disposition of the case (without overt concern for the education of the resident). RESULTS: Of the preceptors' 846 verbal behaviors, 602 (71%) were coded as teacher behaviors, but only 329 (39%) were teacher behaviors that were of the specific types (high-level advice or questions promoting reflectivity, i.e., mindfulness) described in the literature as being most likely to promote learners' reflectivity and transfer of knowledge and skills from a lower level of abstraction to a higher level. CONCLUSION: The results suggest that the 20 perceptors were aware of the importance of "getting residents to think" and did use teaching strategies known to promote transfer. However, their repertoire of strategies was limited. PMID- 8484857 TI - Comparing the academic performances of geriatricians and other family physicians and internists. PMID- 8484859 TI - Medical specialty choice: A selected bibliography with abstracts. PMID- 8484858 TI - Internal medicine residents' attitudes toward giving feedback to medical students. PMID- 8484860 TI - Up-regulation of insulin-like growth factor-I (IGF-I) receptor gene expression in patients with reduced serum IGF-I levels. AB - We have analysed the expression of the IGF-I receptor gene in lymphocytes of patients with low levels of circulating IGF-I (four patients with isolated GH deficiency (IGHD) and one Laron-type dwarf (LTD)) in comparison with a control group exhibiting normal serum IGF-I levels and endocrine profiles. 125I-Labelled IGF-I binding assays were performed on erythrocytes to determine the number of IGF-I binding sites per cell and their dissociation constants. Erythrocytes from patients with IGHD or LTD contained significantly (P = 0.002) more receptors per cell (10.9 +/- 3.1 binding sites/cell), with a reduced affinity (Kd = 0.49 +/- 0.05 nM), than erythrocytes from controls (2.0 +/- 0.4 sites/cell; Kd = 0.14 nM). The levels of IGF-I receptor mRNA in circulating lymphocytes were determined by an RNA template-specific reverse transcription/polymerase chain reaction method. There was a statistically significant increase in IGF-I receptor mRNA levels in lymphocytes from patients with LTD or IGHD when compared with controls (3108.1 +/ 775.9 vs 576.0 +/- 465.7 arbitrary units, P = 0.006). The increased level of IGF I binding due to increased IGF-I receptor gene expression may represent a compensatory up-regulation process activated in response to the low levels of IGF I in the circulation of patients with LTD or IGHD. PMID- 8484861 TI - The human insulin gene-linked polymorphic region adopts a G-quartet structure in chromatin assembled in vitro. AB - The insulin gene-linked polymorphic region (ILPR), located 363 bp upstream of the human insulin gene, is composed of tandem repeats of the consensus sequence ACAGGGGT(G/C)(T/C)GGGG. It has previously been shown that an insulin gene fragment containing the ILPR adopts an altered DNA structure in vitro. Furthermore, oligonucleotides containing the consensus repeat sequence exhibit multiple quadriplex DNA structures. The present study was undertaken to determine whether such altered DNA structures existed within the ILPR when the insulin gene was assembled into chromatin in vitro. Chromatin assembly was achieved using histones and an extract from unfertilized eggs from Xenopus laevis. The presence of altered DNA conformations within the 5' region of the human insulin gene was investigated using the structural probe nuclease P1. Nuclease P1 recognized multiple distinct sites in the 5' flanking region of the human insulin gene in naked DNA. Most of these sites disappeared when the recombinant plasmid DNA was treated with histones and unfertilized egg extract. In the assembled DNA, the ILPR appeared as the major site of nuclease P1 hypersensitivity. Fine-mapping of the multiple reactive sites within the ILPR showed a pattern characteristic of G quartet foldback structures similar to those that have been observed for telomeric DNA. PMID- 8484862 TI - The thyrotrophin hormone receptor of Graves' disease: overexpression of the extracellular domain in insect cells using recombinant baculovirus, immunoaffinity purification and analysis of autoantibody binding. AB - Since the cloning of the TSH receptor (TSH-R), the target autoantigen of Graves' disease, the receptor has been expressed in a variety of eukaryotic cells to obtain a functional molecule. Despite this success, the levels of receptor expression have been marginally higher than the extremely low levels found in thyroid cells, preventing any progress on the purification of the molecule. In this study, the large extracellular region of the TSH-R, without the membrane spanning segments, has been expressed in insect cells using recombinant baculovirus to generate substantial quantities of the receptor protein. A monoclonal antibody previously generated to a bacterial TSH-R fusion protein was used to characterize and monitor the expression of the truncated receptor in insect cells. Two polypeptides of 63 and 49 kDa were recognized as the components of the truncated recombinant receptor. The 63 kDa protein was shown to be the glycosylated form of the smaller, 49 kDa, component. Expression in different insect cell lines showed that an increase in expression of approximately tenfold was apparent in High Five cells when compared with Sf21 cells. Very small quantities of the truncated receptor were secreted by the three insect cell lines examined, with the majority of the molecule being retained within the cells. Immunoaffinity purification of milligram quantities of the truncated receptor was achieved using the monoclonal antibody. The availability of the purified TSH-R has allowed the establishment of an enzyme-linked immunosorbent assay to measure autoantibodies in the sera of patients with Graves' disease. Although the truncated receptor interacts with autoantibodies, our results show that it does not bind TSH and differs in this respect from other glycoprotein hormone receptors. PMID- 8484863 TI - Identification of a functional role for the 3' region of the human oestrogen receptor gene. AB - A well-conserved feature of the steroid receptor gene family is the presence of an exceptionally long 3' untranslated region (UTR). Analysis of this sequence from the human oestrogen receptor (hER) gene showed the presence of a number of AT-rich regions that included thirteen repeats of the ATTTA motif, an element known to have a destabilizing effect in other systems. In the region 3' of the gene there were a further eight copies of this pentamer. Also located in this sequence were two members of the Alu repetitive family in inverse orientation and in a tandem arrangement. Transfection experiments in which the 3' UTR and 3' flanking sequence were included in chloramphenicol acetyltransferase expression vectors revealed a large destabilization effect with several different fragments. This inherent instability appears to be determined by the primary nucleotide sequence but may act in conjunction with other factors. This post-transcriptional regulatory mechanism may contribute to the control of the level of the hER mRNA. PMID- 8484864 TI - Human chorionic gonadotrophin (CG)-induced down-regulation of the rat luteal LH/CG receptor results in part from the down-regulation of its synthesis, involving increased alternative processing of the primary transcript. AB - To elucidate the molecular mechanisms involved in the homologous regulation of LH/chorionic gonadotrophin (CG) receptors, the receptor and its mRNA levels were analysed in the same pseudopregnant rat ovarian samples after human (h)CG-induced down-regulation using a binding assay, ligand blotting, immunoblotting and Northern blotting together with the polymerase chain reaction (PCR). Treatment of the animals with 500 IU hCG resulted in a loss of 125I-labelled hCG binding and the 90 kDa receptor on the ligand and immunoblots within 12 and 24 h respectively, followed by a transient partial recovery on days 4 and 5, while a distinct decline occurred only on day 7 in the controls. Northern blots of total ovarian RNA, as probed with a 293 bp AvaI/HindIII fragment from the extracellular domain of PCR-generated full-length rat LH/CG receptor cDNA, revealed six major mRNAs of 7.0, 4.2, 2.8, 2.0, 1.4 and 1.1 kb. The 4.2 kb mRNA, which was the most abundant, possibly encodes the 90 kDa receptor, while the smaller species probably represent alternatively spliced forms of the LH/CG receptor pre-mRNA, as also supported by the finding that PCR produced three cDNA bands of 2.1, 2.0 and 1.8 kb when oligomers derived from the N and C termini of rat LH/CG receptor cDNA were used as primers and rat ovarian total RNA as a template. Treatment with hCG led to the down-regulation of all six mRNAs in a fashion parallel to the changes in receptor protein. No smaller receptor components capable of binding radiolabelled hCG or receptor antibody appeared on the ligand or immunoblots prior to or during down-regulation or the subsequent transient period of up regulation, suggesting that the smaller mRNA species are translated in minute amounts in vivo or are not translated at all. Laser densitometric analysis of the Northern blots revealed that the amounts of the four smallest mRNA species increased during the period of down-regulation in relation to the 4.2 kb mRNA, and correspondingly decreased during the subsequent period of up-regulation, indicating changes in the alternative splicing of the primary transcript. The data suggest that hCG-induced transient down-regulation of the LH/CG receptor results in part from down-regulation of its mRNA levels, and that changes in alternative processing of the receptor pre-mRNA may play a regulatory role in the expression of functional LH/CG receptor during down- and up-regulation. PMID- 8484865 TI - Changes in progesterone and oestrogen receptor mRNA and protein during maternal recognition of pregnancy and luteolysis in ewes. AB - This study characterized changes in levels of mRNA and protein for endometrial oestrogen receptors (ERs) and progesterone receptors (PRs) during luteolysis and maternal recognition of pregnancy. For cyclic and pregnant ewes, endometrium was collected on days 10, 12, 14, or 16 post-oestrus (4 ewes/day for each status) for the measurement of ER and PR mRNA and protein. The amount of receptor mRNA is expressed in relative units above background, measured from radiographs of dot blot hybridization of total endometrial RNA with ER and PR cDNAs. At hysterectomy, jugular vein blood samples were collected and assayed for progesterone, total corpus luteum weight was recorded and, in vitro, endometrial oxytocin-stimulated inositol phosphate formation was estimated. In pregnant ewes, plasma progesterone increased gradually between days 10 and 16 (P < 0.01), corpus luteum weight was stable at approximately 0.8 g and oxytocin did not stimulate endometrial formation of inositol phosphates in vitro. In contrast, in cyclic ewes, plasma progesterone decreased from day 10 to day 16 (P < 0.01), corpus luteum weight decreased after day 14 to approximately 0.48 g (P = 0.05) and oxytocin stimulated an increase of approximately 1300% in the endometrial formation of inositol phosphates on day 16. cDNAs specifically hybridized with 1.6 and 3.1 kb transcripts for PR mRNA and a 6.5 kb transcript for ER mRNA. In cyclic ewes, the amount of PR mRNA increased from day 10 to maximum levels on days 14-16. The number of PRs decreased from day 10 (2.25 pmol/mg DNA) to day 12 (0.98 pmol/mg DNA) and then increased from day 14 to day 16 (2.8 pmol/mg DNA). In pregnant ewes, PR mRNA levels were greatest on days 10-12 and decreased by approximately 50% by day 16. In contrast, the number of PRs was relatively unchanged from day 10 to day 16 (1.53 to 1.03 pmol/mg DNA). In cyclic ewes, the amount of ER mRNA was lowest at day 10 and increased fivefold by day 16. The number of ERs remained relatively unchanged from day 10 to day 14 (6.07 pmol/mg DNA) and increased by day 16 (16.12 pmol/mg DNA). In pregnant ewes, ER mRNA decreased by approximately 80% from day 12 to day 16. Similarly, the number of ERs decreased from day 10 to day 16 (5.41 to 2.05 pmol/mg DNA). Correlations between ER mRNA and PR mRNA (r = 0.68), ERs and PRs (r = 0.50) and ER mRNA and ERs (r = 0.50) were high (P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8484866 TI - Nutritional enrichment of bakery products by supplementation with nonwheat flours. AB - Bakery products are important ready-to-eat processed foods. The nutritional quality of these products is low because of the inferior nutritional composition of wheat grain per se. This is further accentuated with the use of refined flours in their preparations. Nutritional composition of these products can be improved by using quality wheat for milling, increased extraction rates, air classification of flours to obtain protein-rich nonwheat flours and their products. The flours and protein products of legumes, oilseeds, other cereals, tubers, corn gluten and germ, and rice bran can be used effectively as vegetable protein sources for nutritional enrichment of the bakery products. In this article, recent literature concerning the nutritional composition of major bakery products, sources of vegetable proteins for product enrichment, and modifications in conventional processing methods to maintain the rheological and sensory properties of supplemented bakery products are reviewed critically. PMID- 8484867 TI - Hard-to-cook phenomenon in common beans--a review. AB - Legumes are one of the world's most important sources of food supply, especially in developing countries, in terms of food energy as well as nutrients. Common beans are a good source of proteins, vitamins (thiamine, riboflavin, niacin, vitamin B6) and certain minerals (Ca, Fe, Cu, Zn, P, K, and Mg). They are an excellent source of complex carbohydrates and polyunsaturated free fatty acids (linoleic, linolenic). However, common beans have several undesirable attributes, such as long cooking times, being enzyme inhibitors, phytates, flatus factors, and phenolic compounds, having a "beany" flavor, and being lectins and allergens, which should be removed or eliminated for effective utilization. Grain quality of common beans is determined by factors such as acceptability by the consumer, soaking characteristics, cooking quality, and nutritive value. Acceptability characteristics include a wide variety of attributes, such as grain size, shape, color, appearance, stability under storage conditions, cooking properties, quality of the product obtained, and flavor. Storage of common beans under adverse conditions of high temperature and high humidity renders them susceptible to a hardening phenomenon, also known as the hard-to-cook (HTC) defect. Beans with this defect are characterized by extended cooking times for cotyledon softening, are less acceptable to the consumer, and are of lower nutritive value. Mechanisms involved in the HTC defect have not been elucidated satisfactorily. Attempts to provide a definitive explanation of this phenomenon have not been successful. The most important hypotheses that have been proposed to explain the cause of bean hardening are (1) lipid oxidation and/or polymerization, (2) formation of insoluble pectates, (3) lignification of middle lamella, and (4) multiple mechanisms. Most researchers have reported that the defect develops in the cotyledons. Recently, some authors have suggested that the seed coat plays a significant role in the process of common bean hardening. A better knowledge of cotyledon and seed coat microstructure may lead to a better understanding of the causes of seed hardness. In order to prevent the development of the HTC defect several procedures have been proposed: (1) appropriate storage, (2) controlled atmospheres, and (3) pretreatments. Probably, the most workable solution to the hardening phenomenon may be the development of materials less prone to HTC phenomenon. Decreasing cooking time, increasing nutritive value, and improving sensory properties of seeds with HTC defect would have great nutritional and economical impact.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8484868 TI - [Nursing documentation: consensus in practice (3). The application in stages 2 and 3: Mr. Roozendaal]. PMID- 8484869 TI - [Empathy project in nursing home Bernardus (1). 'Being empathetic is a 24-hour activity]. PMID- 8484870 TI - [Empathy project in nursing home Bernardus (2). Being empathetic with psychogeriatric residents]. PMID- 8484871 TI - [Environment and health care (8). Pollution of the inside environment]. PMID- 8484872 TI - [The BVG (Occupational Board for Health, Mental and Social Affairs) or: the campaign against illness absence and bureaucracy. 'Simpler legislation promised? Where does it say so?]. PMID- 8484874 TI - [Nursing--medicine. How do we define the limits?]. PMID- 8484873 TI - [Safe handling of nitrogen mustard. Risks for nurses in the treatment of mycosis fungoides]. PMID- 8484875 TI - [Stimulating to an age-conscious personnel management]. PMID- 8484876 TI - [Foundation Nursing and Media, or Toward a different nursing image. 'The media did not grow along']. PMID- 8484877 TI - [Environment and health care (10). Risk communication: the nurse as mediator]. PMID- 8484878 TI - [Nursing documentation: consensus in practice (5). The application in stage 4: Trees]. PMID- 8484879 TI - [Transfer as a link in emergency health services]. PMID- 8484880 TI - [Nursing informatics: an orientation]. PMID- 8484881 TI - [Information needs by nurses]. PMID- 8484882 TI - [Knowledge systems: possibilities and pitfalls]. PMID- 8484883 TI - [The VISIT information system (Nursing Information System Individual Home Care)]. PMID- 8484884 TI - [Management information for the primary process]. PMID- 8484885 TI - [Electronic data exchange]. PMID- 8484887 TI - [Nursing informatics: from small town to big city]. PMID- 8484886 TI - [Topics of research]. PMID- 8484888 TI - Hippocampal lesions do not impair negative patterning: a challenge to configural association theory. AB - According to configural association (CAS) theory (Sutherland & Rudy, 1989), an intact hippocampus is required for rats to solve learning problems that are based on "configural" processes. This theory identifies the negative patterning discrimination as a critical example of this type of problem. Rudy and Sutherland (1989) reported disruption of negative patterning following hippocampal formation damage produced by intracranial infusion of a mixture of kainic acid + colchicine (KA + COL). We assessed acquisition of negative patterning in rats with hippocampal damage produced by KA + COL compared with rats with more selective ibotenate lesions of hippocampus. Neither group showed impaired negative patterning relative to controls. A transfer test provided evidence that all groups used configural processes to solve the problem. Thus contrary to CAS theory, the hippocampus is not an important substrate for the operation of configural processes. PMID- 8484889 TI - Effects of amygdala central nucleus lesions on blocking and unblocking. AB - The effects of lesions of the amygdala central nucleus (CN) on blocking and unblocking of appetitive Pavlovian conditioning were examined in 2 experiments with rats. In both lesioned and unlesioned rats, prior pairing of one conditioned stimulus (CS) with a food unconditioned stimulus (US) blocked the acquisition of conditioning to a second CS when a compound of both stimuli was paired with that same US. If the value of the US was increased or decreased when the second CS was added, unlesioned rats acquired substantial conditioning to the second cue (unblocking). Unblocking occurred in lesioned rats only when the US value was increased. In both lesioned and unlesioned rats, unblocking was prevented if the compound cue was paired with the original US prior to the change in US value. These data suggest that the CN is involved in increasing attention to signals for significant events but not in tuning out redundant cues. PMID- 8484890 TI - Amygdala central nucleus lesions disrupt increments, but not decrements, in conditioned stimulus processing. AB - The effects of neurotoxic lesions of the amygdala central nucleus (CN) on changes in the associability of a conditioned stimulus (CS) in appetitive Pavlovian conditioning were examined in 2 experiments with rats. In Experiment 1, CN lesions had no effect on the reduction in the associability of a CS produced by preexposure to that cue (latent inhibition). In Experiment 2, CN lesions prevented the enhancement of the associability of a CS that is normally observed when an inconsistent predictive relation is arranged between that CS and another cue. The results support previous claims that the amygdala CN is involved in broad-based incremental, but not decremental, changes in the processing of CSs in Pavlovian conditioning. PMID- 8484891 TI - Role of the amygdala complex in early olfactory associative learning. AB - Although olfactory associative conditioning in newborn rats produces marked structural and functional changes in the olfactory bulb, recent evidence suggests that extrabulbar circuits must be involved in storing these early memories. The present experiments examined the role of the amygdala complex on early olfactory learning. Bilateral amygdala lesions or sham lesions were performed on Postnatal Day (PN) 5. On PN6, pups were trained in a standard classical conditioning paradigm associating odor with tactile stimulation. Behavioral testing on PN7 revealed that amygdala lesions blocked odor preferences but had no effect on conditioned behavioral activation. Similar sized neocortical lesions did not impair odor preferences. Importantly, amygdala lesion effects on learned odor preferences could be reversed by extensive overtraining. These results suggest that the amygdala complex plays a critical role in modulating associative learning as early as the first postnatal week in the rat. PMID- 8484892 TI - Reversible lesions of the red nucleus during acquisition and retention of a classically conditioned behavior in rabbits. AB - Previous lesion, recording, and stimulation studies implicated the cerebellum and its associated brain-stem circuitry as essentially involved in classical conditioning of discrete, somatic muscle responses. This is a companion to our study of interpositus cooling, which showed that the formation of a memory was prevented. In the present study, we assess the red nucleus for its role in the plasticity associated with learning and memory by using local cooling as a reversible lesion technique. A cooling probe was implanted lateral to the red nucleus. Recording electrodes were implanted in the right red nucleus and the left interpositus nucleus. Animals were trained for 5 days with the cooling probe activated. No behavioral conditioned responses (CR) developed, and multiple unit recordings related to learning did not develop in the red nucleus. However, a learning related model did develop in the interpositus. After 5 days of training while cooling, animals were given 5 days of normal training (cooling probe inactive) to assess retention. Substantial savings were evident when normal training was given. CRs appeared quickly on the first day of normal training, and multiple unit models were present in both red nucleus and interpositus nucleus. These results support the idea that the red nucleus is a necessary efferent for the memory trace formed in the cerebellum. PMID- 8484893 TI - Effects of ablation of the presumed equivalent of the mammalian prefrontal cortex on pigeon homing. AB - Pigeons (Columba livia) with bilateral ablation of the postero-dorsolateral neostriatum and the overlying corticoid were compared with unoperated control subjects in homing from both familiar and unfamiliar sites. Before the operation all the pigeons were subjected to 8 training flights from a site destined to be the familiar one. Postoperatively, the groups did not differ in orientation from the familiar site. In their releases from unfamiliar sites, however, the operated birds oriented in the training flight direction, whereas the control subjects were oriented homeward. In all the releases the homing performance, including both the homing speed and the number of returned birds, was significantly higher in the control group. Thus, the ablated tissue plays a role in homing behavior possibly through mediation of spatial orientation, of olfactory navigation, or of both. PMID- 8484894 TI - Lateral hyperstriatal lesions disrupt simultaneous but not successive conditional discrimination learning of pigeons (Columba livia). AB - In 2 experiments we explored the effects of lateral versus medial laminar lesions of the hyperstriatum in pigeons (Columba livia); medical lesions were largely confined to the hyperstriatum accessorium, and lateral lesions to the hyperstriatum dorsale and hyperstriatum ventrale. In Experiment 1, lateral, but not medial, lesions disrupted acquisition of a simultaneous conditional discrimination; both medial and lateral lesions disrupted reversal of the discrimination. The reversal deficits of the medial and lateral groups were quantitatively similar, and both groups showed exaggerated positional responding. In Experiment 2, neither medial nor lateral lesions disrupted acquisition of a successive conditional discrimination. We conclude that lateral hyperstriatal damage does not obtain a general disruption of conditional learning; we speculate that the lateral hyperstriatum may play a critical role in configural learning. PMID- 8484895 TI - Decreased testosterone levels and accelerated extinction of a conditioned taste aversion in fluid-deprived male rats. AB - The hypothesis that fluid deprivation accelerates extinction of a conditioned taste aversion in male Sprague-Dawley-derived rats by reducing serum testosterone levels was tested. Serum testosterone levels were found to be lower in fluid deprived males than in nondeprived males (Experiments 1 and 2). Exogenous testosterone treatment that results in high physiological levels of serum testosterone slowed the extinction of fluid-deprived gonadectomized males to rates comparable with those of nondeprived sham males (Experiment 3). It was noted, however, that testosterone treatment was less effective in slowing extinction in fluid-deprived gonadectomized males than in nondeprived gonadectomized males even though the serum testosterone levels were the same (Experiments 3 and 4). These results provide strong support for the original hypothesis, but they suggest that fluid deprivation also reduces sensitivity to testosterone. PMID- 8484896 TI - Additivity of taste-specific effects of sucrose and quinine: microstructural analysis of ingestive behavior in rats. AB - Effects of sweet and bitter tastes on ingestion were studied by timing licking responses. Twelve water-deprived rats were given 15-min access to sucrose (S) solutions (0.00%, 1.25%, 2.50%, and 5.00%) with and without quinine (0.01%) and to quinine (Q) solutions (0.00%, 0.0025%, 0.005%, and 0.01%) with and without sucrose (5.00%). Volume ingested and number of licks increased with S and decreased with Q. In response to S, the number of bursts increased, and interlick intervals lengthened. In response to Q, licks to ingest 1 ml of solution, burst number, and percentage of slow licks increased, and burst size decreased. When Q and S were mixed in the same solution, the pattern of ingestive responses manifested attributes of both tastes. Results suggest 2 separate, parallel systems that operate simultaneously to govern rats' licking behavior. One system expresses the effect of S on the pattern of ingestion and the other expresses the effects of Q. PMID- 8484897 TI - Learning that food is inedible in freely behaving Aplysia californica. AB - Freely behaving Aplysia californica can learn that food is inedible. Animals were given access to seaweed tied into canvas and attached to a force transducer. Animals repeatedly found the stimulus, attempted to ingest it, and failed. The force transducer provided an objective record of the number of attempts made by the animal to ingest the stimulus, the length of each attempt, and its intensity (i.e., peak force exerted). Within 2.5 hr, animals showed significant declines in these 3 measures of response to the stimulus. When exposed to the same stimulus the next day, animals showed more rapid declines in responsiveness, which indicate a retention of learning. Training appeared to be specific: Responses to the seaweed Laurencia of animals previously trained on the seaweed Ulva do not differ from the responses of naive animals to Laurencia. PMID- 8484898 TI - Ethanol-induced changes in plasma proteins, angiotensin II, and salt appetite in rats. AB - Sodium depletion in rats elicits a sodium appetite that results from a cerebral action of angiotensin II (ANG II) and aldosterone. Alcohol also activates the renin-angiotensin system, but the mechanism is poorly understood and not related to sodium excretion. In this study, 2.5 g/kg ip ethanol produced a 20% decline in plasma volume and plasma protein concentration in 1-2 hr and elicited salt appetite beginning in 3-4 hr. Blockade of ANG II synthesis in the brain and periphery with the angiotensin-converting enzyme inhibitor captopril eliminated the thirst and salt appetite. Peripheral captopril alone enhanced fluid intake, which indicated that alcohol elevated renin secretion. Ethanol-induced suppression of hepatic plasma protein secretion and the consequent fall in plasma colloid osmotic pressure apparently resulted in hypovolemia and renin secretion, which then produced thirst and salt appetite through an action of ANG II on the brain. PMID- 8484899 TI - Effect of meal composition on mood. AB - The influence of simple carbohydrate, complex carbohydrate, protein, and delayed meal conditions on plasma tryptophan ratios and mood of normal subjects was investigated. In Experiment 1, 27 women consumed 1 of 4 meal conditions, had blood samples drawn, and completed mood assessment measures before and at 5 times during the next 3 hr. Experiment 2 replicated Experiment 1 except that blood samples were not drawn and an additional simple carbohydrate condition was included. The carbohydrate meal conditions elevated blood glucose levels and plasma ratio of tryptophan to other large neutral amino acids over that of the protein condition. A decline in feelings of fatigue and distress occurred 30 min postprandial regardless of condition and persisted for the rest of the study. PMID- 8484900 TI - Ultrasonic vocalization, laryngeal braking, and thermogenesis in rat pups: a reappraisal. AB - In these experiments we tested the hypothesis that the respiratory events underlying rat pup ultrasonic vocalization (USV) facilitate brown adipose tissue (BAT) thermogenesis, as proposed by Blumberg and Alberts (1990). Laryngeal denervation or tracheostomy were used to reduce or eliminate laryngeal braking and prevent USV in 9- to 10-day-old pups during recovery from deep hypothermia and during cooling induced by isolation for 1 hr at room temperature. Both forms of devocalization slowed rewarming of hypothermic pups, but neither had any effects on cooling rate or BAT thermogenesis in normothermic pups that were allowed to cool from 35 degrees C to 29 degrees C. Physiological effects of laryngeal braking on thermogenesis appear to be limited to conditions, such as severe hypothermia, in which ventilatory and oxygen transport functions are compromised. The results have implications for understanding the regulation and evolution of USV. PMID- 8484901 TI - The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock. AB - It has been argued that exposure to inescapable shock produces later behavioral changes such as poor shuttle box escape learning because it leads to the conditioning of intense fear, which later transfers to the shuttle box test situation and interferes with escape. Both fear, as assessed by freezing, and escape were measured in Sprague-Dawley rats 24 hr after exposure to inescapable shock. Lesions of the basolateral region and central nucleus of the amygdala eliminated the fear that transfers to the shuttle box after inescapable shock, as well as the fear conditioned in the shuttle box by the shuttle box shocks. However, the amygdala lesions did not reduce the escape learning deficit produced by inescapable shock. In contrast, dorsal raphe nucleus lesions did not reduce the fear that transfers to the shuttle box after inescapable shock, but eliminated the enhanced fear conditioning in the shuttle box as well as the escape deficit. The implications of these results for the role of fear and anxiety in mediating inescapable shock effects are discussed. PMID- 8484902 TI - Subjective reward magnitude of medial forebrain stimulation as a function of train duration and pulse frequency. AB - The growth of the subjective reward magnitude of medial forebrain bundle stimulation in the rat (Sprague-Dawley) as a function of train duration and pulse frequency was measured in 2 ways: (a) a titration method, which used differences in rate of reward on 2 levers to compensate for differences in the magnitude of the rewards; and (b) a direct method, in which the ratio of the reward magnitudes at the 2 levers was assumed to be given by the ratio of times spent on each lever. The results of the 2 methods agree. Reward magnitude grows as approximately a power function of train duration up to train durations of about 1 s, then declines somewhat over the interval from 2-20 s. The exponent of growth varies from 0.4 to 2.3. With stronger stimulation (higher pulse frequency), peak reward magnitude is bigger, but the saturating train duration is approximately the same. PMID- 8484903 TI - The amygdala is necessary for the expression of conditioned but not unconditioned analgesia. AB - Lesions of the basolateral region and central nucleus of the amygdala prevent conditioned analgesia (Helmstetter, 1992). In general, these regions of the amygdala are more critically involved in the expression of conditioned reactions to aversive events than in the mediation of unconditioned reactions. The impact of amygdala lesions on both conditioned and unconditioned analgesia was explored in Sprague-Dawley rats. The lesions completely prevented the expression of conditioned analgesia, but had no effect on unconditioned analgesia. PMID- 8484904 TI - Purification of basic fibroblast growth factor and alkaline phosphatase from human placenta. AB - Human placenta is an available hospital waste which is known to contain many valuable biochemicals that may be commercially exploited. Using placental tissue previously extracted for haemoderivatives, we purified basic fibroblast growth factor (bFGF), a soluble protein, and placental alkaline phosphatase (PALP), a membrane-linked protein, as a coupled process. bFGF purification comprises three steps: extraction and chromatographies on S-Sepharose and heparin-Sepharose. The final product includes a major 17 kDa and a minor 16 kDa component with a specific activity of 8.0 x 10(6) units/mg yielding 0.5-1.0 microgram/kg of placenta. PALP purification comprises four steps: acidic butan-1-ol extraction and chromatographies on Q-Sepharose, concanavalin A-Sepharose and Q-Sepharose. The purified PALP has a molecular mass of 70 kDa, a specific activity of 800 units/mg and yielded 50 micrograms/kg of placenta. The results show the possibility of purifying substances in placental haemolysed blood, soluble products from placental cellular mass and proteins from the cellular membrane in a one-stream process. PMID- 8484905 TI - Influence of the reaction medium on enzyme activity in bio-organic synthesis: behaviour of lipase from Candida rugosa in the presence of polar additives. AB - Lipase from Candida rugosa immobilized on Celite was employed as the biocatalyst in order to examine the effect of the reaction medium upon enzymic activity and selectivity. As the model reaction, transesterification between tributyrin and pentan-2-ol in iso-octane (2,2,4-trimethylpentane) was chosen. A small amount of water (0.05%, v/v) was added to the reaction medium. Enhanced transesterification yields and increased selectivity of the lipase could be obtained by manipulating the microenvironment of the catalyst. Addition of 0.2% NN-dimethylformamide allowed a 93% higher ester yield compared with that obtained when no extra addition was made. Under the same conditions, the ratio of the amount of transesterification product over the amount of hydrolysis product after 48 h, became 52% higher than the ratio determined in the absence of additives. It was concluded that addition of compounds that have low logP3 (P is the partition coefficient in the octanol/water two-phase system) values and high dielectric constant was advantageous in order to favour transesterification over hydrolytic processes. PMID- 8484906 TI - Cyclomaltodextrin glucanotransferase from Bacillus circulans E 192: nitration with tetranitromethane. AB - Nitration of tyrosine residues was performed on Bacillus circulans E 192 cyclomaltodextrin glucanotransferase (CGTase) using tetranitromethane (TNM). A maximum of 15 out of 28 tyrosine residues is modified with 8 mM TNM, entailing a concomitant loss of enzymic activity and tryptophan fluorescence. Spectroscopic studies suggest that these two phenomena are related to an impairment of the enzyme conformation as a consequence of the tyrosine nitration. The presence of 5 mM acarbose during the CGTase nitration results in the protection of one tyrosine residue and the rate of inactivation is reduced 9.4-fold. These results support a contribution of a tyrosine residue in the CGTase catalytic site. The nitration of CGTase also entails a decrease in the enzyme's affinity for a beta-cyclodextrin (beta-CD) co-polymer. Kinetic and analytical investigations on isolated modified enzymes support the concept that this phenomenon is unrelated to the modification of tyrosine residues, but rather concerns a side reaction of the reagent occurring at the raw-starch-binding site of the CGTase. PMID- 8484907 TI - Peptide synthesis catalysed by Pseudomonas aeruginosa elastase. AB - Pseudomonas aeruginosa elastase was used for peptide-bond synthesis with benzyloxycarbonylalanine and amino acid amides as nucleophilic substrates. Dipeptide-bond synthesis was observed only for hydrophobic amino acid amides. The rate of peptide synthesis, measured by h.p.l.c., was in the decreasing order: Phe > Leu > Tyr > Val, Ile > Ala, which is consistent with the decreasing order of hydrolysis rates of the corresponding tetrapeptides Ala-Ala-Xaa-Ala. In contrast with thermolysin, Ps. aeruginosa elastase permits the synthesis of tyrosine containing peptides with tyrosine in the P'1 position. Furthermore, the rates of synthesis for other hydrophobic amino acid amides are higher with elastase than with thermolysin. PMID- 8484908 TI - Exo-glucosidase activity and substrate specificity of the beta-glycosidase isolated from the extreme thermophile Sulfolobus solfataricus. AB - The enzyme with beta-galactosidase activity from Sulfolobus solfataricus strain MT-4, like other enzymes of this type isolated from thermophilic sources, has broad specificity for beta-D-gluco-, fuco- and galacto-sides. The beta galactosidase activity was purified by a new procedure that improved yields (44%) and final specific activity (182 units mg-1 at 75 degrees C using chromogenic beta-D-galactoside as substrate). The enzyme hydrolysed a large number of beta linked glycoside dimers and oligomers; chromogenic beta-glucosides and beta fucosides are the preferred substrates, and kinetic analysis indicated that they bind to a common catalytic site. The order of catalytic efficiency was beta 1-3 > beta 1-4 > beta 1-6 and cellotetraose > cellotriose > cellobiose for glucose dimers and oliogomers respectively. The cleavage occurred at the non-reducing end of the oligosaccharide, and the enzyme showed noticeable specificity also for the aglycone part of substrates. From these results the enzyme from S. solfataricus strain MT-4 is defined as a true glycosyl hydrolase with remarkable exo glucosidase activity and it is designated S beta-gly. PMID- 8484909 TI - Chitinolytic digestibility of cross-linked chitosan gels by an enzyme complex from Streptomyces kurssanovii. AB - The action of a microbial chitinolytic enzyme complex from Streptomyces kurssanovii on chitosan gels with various degrees of cross-linking and on the O derivatives of the gels was examined. The rate of digestion of the gels was shown to depend on the degree of cross-linking as well as on the size of the O substituent, decreasing greatly with a rise in substitution. PMID- 8484910 TI - [Evolution of the microbiological parameters of cured ham]. AB - The main microbiological and physico-chemical parameters in dry-salted ham previously selected were determined along the elaboration process. All determinations were performed at 2 levels: surface and internal. All bacterial groups showed a similar behaviour, increasing along the first stages up to the third month of drying, then decreasing to numbers similar to the initial ones. Only the halotolerants maintained fairly high numbers during last stages. Some groups were almost absent at internal levels. The hazardous bacteria showed different behaviour: whereas the faecal streptococci were fairly abundant during the whole study, coliforms almost disappeared at the final stages. During the elaboration process at different stages of ripening they were analysed in order to know the moulds population at surface level. Aspergillus and Penicillium were the dominant genera. The latter, mainly represented by 10 species, dominated during the first stages of elaboration. Aspergillus was present throughout the whole making process. The glaucus group was clearly dominant at the final stages due to the low aw values together with the high NaCl percentages. Aspergillus halophilicus was the most abundant species identified (18%) and the most frequently isolated at the final stages. PMID- 8484911 TI - [Experimental design and data handling in food microbiology]. AB - A discussion on the problems associated with designing experiments in Food Microbiology research is presented. After defining what is meant by Design of an Experiment, a series of questions are raised that, once answered, will help in properly designing the experiment. It is emphasized the chain research-design model-analysis-design and the danger in blindly using well-known designs and canned programs. PMID- 8484912 TI - [Lipid- and protein-degrading processes during the maturation of ham]. AB - In the present work we review the main degradative pathways for lipids and proteins along the ripening of dry cured hams, with special emphasis on Iberian pig hams. Maximum proteolytic activity is found around the first stages (salting) and specially at the dryer. Lipolytic activity seems to be also higher in this stage. During the steps that follow the post-salting period the oxidation seems to be activated. The products from proteolytic and lipolytic processes might react among each other during the final steps in the cellar. PMID- 8484914 TI - [Monographic issue on foods]. PMID- 8484913 TI - Biochemical and microbiological events of Parma ham production technology. AB - Parma ham technology relies on a few basic points. They are: a fresh meat substantially free of microbial deep contamination, a relatively long phase (up to 100 days) at cold temperatures at the beginning of processing, an uncovered muscular surface as reduced as possible, a long period of maturation. The final product, the matured ham, is the result of a slow process of dehydration which, combined with a limited penetration of salt into the muscles, lowers the water activity to values around 0.90. Surface bacterial contamination is mainly made up by Enterobacteriaceae and Pseudomonadaceae. Among them E. agglomerans and S. liquefaciens are able to grow at 2 degrees C and salt concentrations up to 7.5% and can be responsible for taint development. Micrococci penetrate into the meat during salting and can reach values of 10 x 6 but decrease substantially towards the end of maturation. Maturation, from a biochemical point of view, is characterized by hydrolytic phenomena interesting nitrogen compounds and fats. As a result free amino acids, non protein nitrogen, volatile fatty acids and carbonylic molecules are produced. Such products are important for the development of typical organoleptic characters. PMID- 8484915 TI - [Technology for the production of cured ham]. AB - The main factors to be considered in the preservation of hams are: pH level, temperature and level of water activity. There are four different stages in the process of curing. (1) Selection of the raw material: the longer the time of curing, the higher the percentage of marbled fat has to be (to control the drying process). The temperature within the ham should be kept between 1 and 3 degrees C. (2) In the salting stage, nitrifiers are added and the hams are either coated with salt for 1 day per kg of ham, or a specific quantity of salt is applied in a massager or a tumbler. (3) In the post-salting stage, hams are kept below 5 degrees C for at least one month. During this stage salt diffuses throughout the ham. Some dehydration, and selection of bacteria occurs. On the outside of the ham fungi will grow, while inside Micrococcaceae are the dominant flora. Finally the hams pass to a drying-maturing stage. As the level of water activity falls, the temperature is increased, causing proteolysis and lipolysis, which are important for the development of texture and flavour of the ham. PMID- 8484916 TI - [Utilization of lactic bacteria in the control of pathogenic microorganisms in food]. AB - The lactic acid bacteria have the potential to inhibit the growth of pathogenic and spoilage bacteria and the possibility exists of using them to improve the hygienic quality and to extend the shelf-life of different foods. Among the many inhibitory substances produced by the lactic acid bacteria, the bacteriocins are of particular interest. It has been the objective of this work to review the bacteriocins produced by lactic acid bacteria from the genera Lactococcus, Lactobacillus and Pediococcus, as well as Leuconostoc and Carnobacterium to understand their relevant biochemical, immunological and genetic characteristics. The lactic acid bacteria may also express foreign genes codifying metabolites with antimicrobial activities against foodborne pathogens of interest, and this will also permit hypothesize about theoretical and experimental models of microbial antagonism mediated by the lactic acid bacteria. PMID- 8484917 TI - [Incidence, behavior and control of Aeromonas hydrophila in meat and dairy products]. AB - This review deals with several aspects of Aeromonas hydrophila and other motile Aeromonas species associated with foodborne illness. Although it is mainly dedicated to the factors affecting growth and survival of this species in foods of animal origin, information on other topics is also provided. This paper includes sections on: Taxonomy, diseases caused by Aeromonas, virulence factors, reservoirs and prevalence in foods and water, factors affecting growth and survival, isolation and identification, and control measures. PMID- 8484918 TI - Incidence and control of Campylobacter in foods. AB - Campylobacter jejuni is known as the most common human enteropathogen in developed countries. The epidemiology of the organism has now been adequately determined and indicates that campylobacteriosis is a zoonotic disease. Pets, water, and contaminated foods are the main sources of sporadic infections in humans, and no single animal food source can be excluded as a potential vehicle for infection of humans. The available information indicates that 50 to 70% of cases of enteritis in man are associated with poultry. Cross-contamination and improper handling and cooking of foods of animal origin account for the majority of disease. Hygienic measures must be applied in order to reduce the incidence of campylobacteriosis in humans. PMID- 8484919 TI - [Applications of molecular biology techniques for the control of aflatoxin contamination]. AB - Aflatoxins are mycotoxins produced by species of Aspergillus flavus group. These toxins have received increased attention from the food industry and the general public because they shown a high toxicity against humans and animal. Different methods are applying to control the aflatoxin contamination. But these conventional methods do not seem to resolve the problem. So, new methods using techniques in biotechnology are now being developed: a) Inhibit the biosynthetic and secretory process responsible for aflatoxin contamination. b) Using biocompetitive agents that replace aflatoxigenic strains with non aflatoxigenic strains in the field. c) Using genetic engineering techniques to incorporate antifungal genes into specific plant species. PMID- 8484921 TI - Predictive modelling of growth, survival and inactivation of pathogenic and spoilage organisms in foods. PMID- 8484920 TI - [Genetic manipulation of the synthesis of fungal enzymes for use in the food industry]. AB - Food industries use a great variety of enzymes as additives. The main percentage of them are produced by species of filamentous fungi. In this review we present the strategies to purify and overproduce this kind of enzymes using recombinant DNA techniques. PMID- 8484922 TI - Structure of 1-(4-[2-(diethylamino)ethoxy]phenyl)-2-(4-methoxyphenyl)-1 phenylethan- 1-ol, the non-steroidal antiestrogen MER25. AB - C27H33NO3, M(r) = 419.6, monoclinic, P2(1)/a, a = 22.833 (6), b = 9.370 (3), c = 11.434 (4) A, beta = 110.71 (8) degrees, V = 2288.2 A3, Z = 4, Dx = 1.22 g cm-3, lambda (Cu K alpha) = 1.54178 A, mu = 5.8 cm-1, F(000) = 904, T = 138 K, R = 0.049 for 3265 observed reflections. The molecule of MER25 assumes an extended conformation with rings alpha' and beta in an antiperiplanar (trans) conformation giving the solid-state conformer a closer resemblance to the estrogenic (E) isomer of tamoxifen than the antiestrogenic (Z) isomer. The geometrical features of the triarylethan-1-ol moiety are comparable to related structures but the orientations of the phenyl rings are different. The O-C-C-N segment in the (diethylamino)ethoxy side chain has the uncommon trans conformation instead of the more commonly observed gauche conformation seen in tamoxifen and many of its derivative structures. The amino N atom forms a hydrogen bond with the hydroxyl group of a neighboring molecule to form an infinite chain along the b axis. PMID- 8484923 TI - Structure of ethyl phenyl selenone. AB - C8H10O2Se, M(r) = 217.13, monoclinic, P2(1)/n, a = 9.511 (2), b = 15.741 (3) c = 11.467 (2) A, beta = 91.31 (2) degrees, V = 1716.3 (6) A3, Z = 8 (two molecules per asymmetric unit), Dx = 1.68 Mg m-3, lambda (Mo K alpha) = 0.71069 A, mu = 4.19 mm-1, F(000) = 864, T congruent to 295 K, R(obs) = 0.060 for 1944 unique reflections with I > 2 sigma (I). The two molecules in the asymmetric unit are very similar; they differ only in the conformation of the ethyl side chain. There is considerable disorder in one molecule, that possibly can be represented by torsion about the Se-C(ethyl) bond. In each case the O atoms of the SeO2 group lie near the plane of the phenyl group. Se-O ... H-C interactions appear to be the only significant intermolecular interactions. These involve an H atom of the alpha-C atom of the ethyl group in addition to the H atoms of the phenyl group. PMID- 8484924 TI - Structure of the molecular complex of anthracene with 1,8:4,5 naphthalenetetracarboxylic dianhydride. AB - C14H10.C14H4O6, M(r) = 446.42, monoclinic, P2(1)/a, a = 17.572 (10), b = 7.727 (4), c = 7.398 (4) A, beta = 101.90 (4) degrees, V = 982.9 (9) A3, Z = 2, Dx = 1.508 Mg m-3, lambda (Mo K alpha) = 0.71069 A, mu = 0.100 mm-1, F(000) = 460, T = 293 K, R = 0.050 for 1429 unique reflections with I > 3 sigma (I). The molecules stack with alternating rows of anthracene and dianhydride molecules. The two types of molecule do not lie parallel to each other in these stacks, possibly as a result of interactions between the peripheral H atoms of the anthracene and O atoms of the anhydride. PMID- 8484925 TI - Structures of quinone imine metabolites related to the anti-cancer drug amsacrine. AB - (5): N-(9-Acridinyl)-3-methoxy-1,4-benzoquinone monoimine, C20H14N2O2, M(r) = 314.3, monoclinic, P2(1)/c, a = 13.451 (8), b = 7.007 (4), c = 17.864 (12) A, beta = 117.26 (4) degrees, V = 1497 (2) A3, Z = 4, Dm = 1.36 (1), Dx = 1.395 g cm 3, Mo K alpha, lambda = 0.71069 A, mu = 0.99 cm-1, F(000) = 656, T = 138 (5) K, R = 0.049 for 1556 reflections. (8): N-(9-Acridinyl)-2-methoxy-1,4- benzoquinone monoimine, C20H14N2O2, M(r) = 314.3, triclinic, P1, a = 9.365 (1), b = 13.318 (2), c = 6.918 (3) A, alpha = 96.45 (3), beta = 105.30 (2), gamma = 110.11 (1) degrees, V = 761.6 (4) A3, Z = 2, Dm = 1.35 (1), Dx = 1.371 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 0.98 cm-1, F(000) = 328, T = 292 (1) K, R = 0.075 for 1009 reflections. (13): N-(9-Acridinyl)-5-dimethylamino-2- methoxy-1,4 benzoquinone monoimine, C22H19N3O2, M(r) = 357.4, triclinic, P1, a = 8.091 (7), b = 10.078 (2), c = 11.716 (3) A, alpha = 108.39 (2), beta = 99.63 (4), gamma = 95.87 (3) degrees, V = 881.4 (9) A3, Z = 2, Dm = 1.33 (1), Dx = 1.347 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 0.95 cm-1, F(000) = 376, T = 173 (5) K, R = 0.034 for 1460 reflections. The molecular geometries are described and discussed. PMID- 8484926 TI - The TAPS Project. 8: Design of the research study on the long-stay patients. PMID- 8484927 TI - The TAPS Project. 9: The reliability of the Patient Attitude Questionnaire. AB - The development of the hospital and community versions of the Patient Attitude Questionnaire is described. The instrument rates the attitudes of psychiatric patients towards their treatment settings and staff, and is framed specifically to assess attitudinal change during the transfer of patients from hospital. For the items rated using the kappa coefficient of agreement, the mean test-retest reliability value was 0.51, and the average inter-rater value was 0.82. This study shows that long-term psychiatric patients are able to give clear and consistent views about their living arrangements--views that should be sought and respected by staff. PMID- 8484928 TI - The TAPS Project. 10: The long-stay populations of Friern and Claybury hospitals. The baseline survey. AB - As part of the TAPS project, the baseline long-stay populations of Friern and Claybury Hospitals were compared using the TAPS assessment schedules. Each hospital has reduced bed numbers by two-thirds, and although the two have been subjected to different influences, their remaining long-stay patients were similar, and characterised by severe problems with hygiene, florid psychotic symptoms, a high prevalence of negative symptoms, and impoverished social networks. PMID- 8484929 TI - The TAPS Project. 11: The selection of patients for reprovision. AB - The selection of patients for community reprovision during the first three years of an active closure programme at two large mental hospitals in the North East Thames Regional Health Authority was studied. It was found that a strong selection bias was operating: the patients selected were significantly younger, had spent less time in full-time psychiatric care, were less likely to have a diagnosis of schizophrenia, had larger social networks, and were more likely to want to leave hospital. PMID- 8484930 TI - The TAPS Project. 12: Crime, vagrancy, death and readmission of the long-term mentally ill during their first year of local reprovision. AB - The extent of crime, vagrancy, death, and readmission in a prospective cohort of long-term mentally ill patients was measured during their first year out of hospital. All 278 long-stay psychiatric patients discharged during the first three years (1985-1988) of the closure of Friern and Claybury Hospitals were included. One patient was imprisoned, one committed suicide, and one became vagrant; five others may also have become vagrant. The mortality rate was similar for the leavers and their matched controls, who remained in hospital. There was one suicide among the matches. Mental deterioration most often caused readmission. On recovery, most patients returned to their community home. Six per cent of the cohort were readmitted and have remained in hospital for a year or more. With careful planning and a financial 'dowry' for each patient, the closure of large mental hospitals does not lead to a marked increase in vagrancy, crime, and mortality for the long-term mentally ill. However, the patients who have yet to leave have more problems of social behaviour and are likely to be more difficult to resettle. PMID- 8484931 TI - The TAPS Project. 13: Clinical and social outcomes of long-stay psychiatric patients after one year in the community. AB - The first prospective, controlled study of a large, long-stay, in-patient population as their hospital services were reprovided in the community is reported. Two-hundred-and-seventy-eight patients were matched individually with similar patients who remained in hospital. Clinical and social outcomes over a one-year follow-up are presented for the first three years of the reprovision process. Compared with matches, the leavers at follow-up had more diverse social networks that contained a higher proportion of contacts named as friends. The care facilities in the community allowed more opportunities for patient autonomy than the hospitals across all aspects of the environments measured. At follow-up, more leavers than matches wanted to remain in their current placement, while fewer leavers than matches said there was nothing they liked about their current placement. More leavers than matches found their medication helpful. PMID- 8484932 TI - Evaluating the transfer of care from psychiatric hospitals to district-based services. PMID- 8484933 TI - The TAPS Project. 7: Mental hospital closure--a literature review of outcome studies and evaluative techniques. AB - Various techniques have been used to assess the results of 'deinstitutionalisation'. This paper reviews these outcome studies, most of which have concluded that a new long-stay group will replace the old long-stay patients, and that a residual group of ageing patients, mostly with organic syndromes, is difficult to accommodate in the community. PMID- 8484934 TI - A tribute to Jack Anderson (1917-1992) PMID- 8484935 TI - The physician as professional and the physician as honest businessman. PMID- 8484936 TI - Remobilization of paralyzed vocal cord by anticus-lateralis muscle suturing. AB - A new method of dynamic reconstruction by suturing the cricothyroid (anticus) and the lateral cricoarytenoid (lateralis) muscles was devised for the treatment of unilateral recurrent laryngeal nerve paralysis. Eighteen adult dogs underwent this surgical procedure after sectioning a recurrent laryngeal nerve. Immediate postoperative observations revealed a marked increase in tension of the paralyzed vocal cords and remobilization to the median line of 17 of 18 dogs. More than 4 months later, fiberscopic examination revealed a satisfactory adduction of the cords. Electrophysiologic and histologic examination showed reinnervation of the affected lateralis muscle by the external branch of the superior laryngeal nerve. The clinical applications of this surgery may serve as a dynamic reconstruction for unilateral recurrent laryngeal nerve paralysis. PMID- 8484937 TI - Laryngeal reconstruction in children. Assessment of vocal quality. AB - During the past decade, the outcome of laryngotracheal reconstruction in children has improved substantially regarding airway patency. Now that we feel comfortable with airway results, attention should be directed toward vocal quality. The aims of this article are to present our evaluation process, which has been developed during the past 3 years, and our assessment of results. Six patients who underwent successful laryngotracheal reconstruction and could be examined preoperatively and postoperatively were studied. Information about disease and reconstruction techniques was recorded. Vocal quality assessment was done using psychoacoustic evaluation and objective techniques, including acoustic analysis. Children offer a specific challenge, especially when their chronological or developmental age is younger than 3 years. Objective assessment still lacks the ability of using cooperative patients, and adequate samples for acoustic analysis are difficult to obtain and standardize. Preoperative abnormalities continued to persist postoperatively. Laryngotracheal reconstruction is instrumental in making oral communication possible, but the vocal quality is disturbed in most patients. PMID- 8484938 TI - A comparative study of speech after total laryngectomy and total laryngopharyngectomy. AB - Quality of voice is an important factor in the consideration of treatment for advanced laryngeal cancer. This prospective study compared the speaking proficiency of patients who used the Blom-Singer valve after total laryngectomy and after total laryngopharyngectomy with jejunal graft reconstruction with that of a group of normal subjects. The total laryngectomy group demonstrated excellent communication ability both face-to-face and on the telephone. They exhibited superior scores for objective intelligibility, subjective intelligibility, acceptability, and intonation when compared with the total laryngopharyngectomy group. Both surgical groups produced similar amplitude and frequency parameters during normal conversation but had limited reserve when these functions were stressed. Despite these quantitative variations, patient acceptance was very high in both surgical groups. These results serve as a foundation for the evaluation and improvement of rehabilitation techniques. PMID- 8484939 TI - Experimental mandibular regrowth by distraction osteogenesis. Long-term results. AB - The use of gradual distraction to grow bone (distraction osteogenesis) has gained widespread orthopedic acceptance, but has only recently been applied to craniofacial skeletal defects. The use of bifocal distraction osteogenesis to fill experimental segmental mandibular defects with regenerate bone was recently reported. Though all canines in that study demonstrated normal oromandibular function, they were observed for only 4 weeks following defect closure. The study that is now reported describes the long-term (12-month) functional, morphologic, and biomechanical results when bifocal distraction osteogenesis was applied to the same model. In this long-term study, three canines had 2.5-cm unilateral segmental mandibular body defects filled with structurally stable bone using bifocal distraction osteogenesis. These dogs exhibited normal oromandibular function for 1 year following segment regrowth and external fixator removal. Macroscopic and histologic evaluation of the regrown segments revealed a re formation of the cortical and medullary architecture. Stress testing demonstrated the average ultimate strength of the regrown segment at 53 MPa, which corresponded to 77% +/- 5.7% of normal mandibular bone. The data suggest that clinical trials applying this technique to segmental mandibular reconstruction are warranted. PMID- 8484940 TI - Predicting occult lymph node metastasis in parotid cancer. AB - To determine the factors predictive of occult cervical metastases, we retrospectively reviewed the charts of 99 previously untreated patients with a primary parotid malignancy who underwent elective neck dissection between 1960 and 1985. Univariate and multivariate analyses were performed to determine the predictive value of 11 factors. The univariate study found facial nerve paralysis, extraparotid extension, and perilymphatic invasion statistically significant. In the multivariate analysis of preoperative factors, facial nerve paralysis was most predictive of occult disease. If the variable pool was expanded to include a fine-needle biopsy, tumor grade became the most important preoperative variable. When the analysis was further expanded to include a parotidectomy, the most influential factors were patient age, perilymphatic invasion, and extraparotid tumor extension. This report identifies the variables predictive of occult neck disease in parotid cancer. PMID- 8484941 TI - Peritonsillar abscess. Clinical and microbiologic aspects and treatment regimens. AB - This prospective study shows that acute peritonsillar abscess can be successfully treated by three-point puncture and aspiration. The results (recurrence in 19%) are comparable with published data on drainage of the peritonsillar space through the incision procedure. By proper selection of patients, the rate of recurrences can be further reduced. Because the occurrence of Streptococcus pyogenes in the aspirate seems to be associated with a favorable prognosis of therapy with puncture and antibiotics only, testing for the presence of this bacterial species might give a useful clue to the type of treatment needed. If the bacterial culture shows mixed aerobic and anaerobic flora, but not S pyogenes, and if the patient has a history of recurrent tonsillitis, incision or proceeding directly to tonsillectomy may be the best therapeutical choice. PMID- 8484942 TI - Pediatric cochlear implantation. Radiologic observations of skull growth. AB - We investigated the effects of long-term implantation of auditory prostheses on skull growth in young animals. Four monkeys were implanted with dummy cochlear implants at 6 months of age. To simulate implantation in children, the bed for the receiver-stimulator or interconnecting plug was drilled across a calvarial suture down to the underlying dura. Plain skull roentgenograms were periodically taken to monitor head growth for up to 3 years after implantation. These longitudinal measurements revealed no significant asymmetric skull growth. Postmortem measurements using computed tomographic scans confirmed these results and showed no significant difference in the intracranial volumes between the implanted and control sides of each animal or between experimental and nonimplanted control monkeys. These results suggest that long-term cochlear implantation in very young children will not cause any significant deformity of the skull. PMID- 8484943 TI - The male facelift. An analysis of 115 cases. AB - Based on the anatomic differences in female and male cervicofacial skin, a retrospective study of 115 male facelifts was undertaken to identify those factors that contributed to a satisfactory esthetic result and the avoidance of complications. Incision modifications are reported, as well as the need for ancillary procedures (in 37% of the patients) to obtain facial rejuvenation. An increased incidence of hematomas (9.6%) was noted. PMID- 8484944 TI - Skin excision revision rhinoplasty. AB - A technique of skin excision revision rhinoplasty is described for application in patients undergoing rhinoplasty. This group of patients includes those with soft tissue polly beak deformities and a variety of other difficult post-rhinoplasty deformities. Horizontal nasal dorsal skin excision affects tip elevation and eliminates supratip fullness, while vertical midline nasal dorsal skin excision enhances tip definition, decreases dorsal height, and eliminates supratip fullness. We describe several patients who underwent either horizontal or vertical nasal dorsal skin excision for a variety of cosmetic deformities following conventional closed and open rhinoplasty. The techniques presented herein are meant to be added to the list of techniques available to the revision rhinoplasty surgeon rather than to replace existing techniques. PMID- 8484945 TI - Facial nerve paralysis from slag injury to the ear. AB - Transtympanic facial nerve paralysis resulting from a penetrating injury through the external auditory canal is a rare occurrence. The common mechanism of paralysis is direct fracture or penetration of the fallopian canal. Slag injuries of the ear caused by hot sparks or molten metal are well known to otolaryngologists because they often result in chronic tympanic membrane perforations and chronic otorrhea. We have encountered two unusual cases of transtympanic slag injury to the ear that resulted in facial nerve injury. In one patient, a significant inner ear injury also occurred. A pathophysiologic mechanism of thermal injury is proposed, and the use of ear protection in welders is discussed. PMID- 8484946 TI - Actinomycosis otomastoiditis. AB - We reviewed the reported experience with actinomycosis otomastoiditis in the international literature, along with a recent case from our experience. All recently reported cases presented with persistent drainage and partial response to multiple courses of antibiotics. Diagnosis was uniformly made postoperatively, and the outcome was excellent following a prolonged course of antibiotic treatment. PMID- 8484947 TI - The otolaryngologist and the patient with velocardiofacial syndrome. AB - Velocardiofacial syndrome is the most common syndrome associated with clefting of the secondary palate. The endoscopically diagnosed occult submucous cleft palate is the most common palate anomaly associated with this syndrome. Patients with velocardiofacial syndrome present a special challenge to the otolaryngologist, who must be familiar with the diagnostic and therapeutic aspects of this syndrome. We report the findings in 21 patients with velocardiofacial syndrome. Only 11 (52%) had the typical manifestations, and others had only partial phenotype. Adenoidectomy must be avoided in these patients, since undiagnosed occult and overt submucous cleft palate are the most common cause of velopharyngeal insufficiency after adenoidectomy. Three patients had aberrant carotid arteries. This anomaly must be excluded by nasoscopy and computed tomographic scanning before pharyngeal flap surgery is considered in these patients. Criteria for exclusion of high-risk patients from adenoidectomy are presented and discussed. PMID- 8484948 TI - Pathologic quiz case 2. Laryngeal syngamosis. PMID- 8484949 TI - Pathologic quiz case 1. Spindle cell lipoma. PMID- 8484950 TI - Goode T tubes. PMID- 8484951 TI - [Developing a health mind-set--description of caritative health promotion]. AB - This investigation describes health promotion from a caring science perspective. Caring is defined as an act of "caritas" c.e. love and mercy (Eriksson 1991). The investigation is theoretical and comes as a result in a model for health education. The model will be empirically tested in the future further on. The research method is qualitative and descriptive consisting of three processes: the abductive, deductive and inductive. This method was created by Charles Peirce (1839-1914). The inductive process will be implemented by testing the model. Abduction is the process of forming an explanatory hypothesis. The abductive hypothesis of this investigation is formed in the following way: "the kind of mood od mind, the kind of health". Main emphasis has been in examining the meaning of the mood of mind for ones health and the possibilities to develop it. The following question were asserted; 1. What is meant by the mood of mind? 2. What attributes are required in order to talk about health's mood of mind? 3. What are the possibilities of developing the mood of mind as a way for health education? The result of this investigation is presented as a model for health promotion. The model is upbuilt by the caritative elements featuring belief, hope, love and the concept of virtue. The model shows the consequences for a human beings daily living. In the case of having too much belief a human being may develop some kind of health fanatism. In the case of having too much belief a human being may develop some kind of health fanatism. In the case of having too much hope a human being puts forward the decisions about health for tomorrow. In the case of having too much love it may lead to a irresponsible lifestyle. An assumption is that a balance between belief, hope and love leads in choosing health, planning for health and living in health. PMID- 8484952 TI - [Life control, the core of being healthy. Theoretical-empirical definition of the concept "life control"]. AB - In this article the concept 'life control' is being analysed and defined. A need to define the concept 'life control' emerged during a research that deat with a human being's descriptions being healthy. 'Life control' turned out to be the central category and the main concept organising the whole data. The data were collected by focused interviews (N = 60). Those interviewed represented five different styles of 'life control'. One of these styles that were discovered in the research was chosen as the basis of the conceptual analysis. This style was characterised by 'laissez faire' attitude towards life. Hybrid model was used as the theoretical frame of reference in the conceptual analysis. Thorough study of Finnish and foreign literature about 'life control' leads into an explicit definition of 'life control' describing the data collected by focused interviews: 'Life control' is an individual's basic belief concerning the possibilities to control the course of human life and the extent of this control. An individual either controls his/her life quite independently and completely or only to a certain extent, or it is controlled by factors beyond the influence of a human being. The definition of the 'life control' -concept in the sense that it displays basic beliefs should be examined by studying people's way of thinking with the help of interviews, essays, questionnaires or analysis of autobiographies. PMID- 8484953 TI - [Phenomenography--a way to do qualitative research]. AB - The purpose of this paper is to describe and evaluate theoretical principles, possibilities and limits of the qualitative research method called phenomenography. The article is based on a literature review. Phenomenography is a research methodology initiated by Ference Marton and his research group in Sweden in the 1970s. Unlike phenomenology, phenomenography is not a philosophical school. It is a pragmatic method for doing qualitative research. In phenomenography, the aim of research is to describe the qualitatively different ways in which people perceive the world around them (the second-order perspective). The most common method of data collection is thematic interviewing. The results are categories of description representing the different conceptions of a phenomenon found among a certain population. Phenomenography is a useful method for qualitative analyses. However, it has also been criticized for a static view of human thought--a criticism that points toward the risks of relying on a single method in qualitative research. PMID- 8484954 TI - [Opinions of student nurses and student care assistants concerning adequate care of a patient with dementia, and how to learn it]. AB - The research investigated the views which the student nurses and the student care assistants had received from their studies concerning the care of demented patients. It also dealt with the opinions they had received about the good care of a demented patient. The data was gathered by interviewing 11 student care assistants and 14 student nurses who were to finish their studies within a month. The data was analyzed by using qualitative analytical methods. The student care assistants emphasized the care itself and the patient more than the student nurses did. The student care assistants emphasized the rehabilitation and the physical care. While evaluating their studies, the student nurses considered the teaching in the nursing school in a more negative way than the student care assistants. Both groups regarded the prevailing nursing practice as a difficulty in learning the good care of the demented patients. PMID- 8484955 TI - The effect of alpha-interferon on thymidine, uridine, and leucine uptake and ultrastructure of peripheral blood mononuclear cells from multiple myeloma patients. AB - The effect of IFN alpha-2b on thymidine, uridine, and leucine uptake was examined on peripheral blood mononuclear cells (PBMC) of healthy donors and 15 patients with multiple myeloma (MM). In addition, the surface ultrastructure of the cells incubated without or with IFN alpha-2b was examined with a scanning electron microscope. The results showed that IFN had no effect on thymidine, uridine, or leucine uptake of unstimulated MM and control PBMC. On the other hand IFN inhibited thymidine, and uridine uptake of PWM-stimulated MM PBMC, but had no effect on healthy donor stimulated PBMC. IFN inhibited also thymidine and uridine uptake in PHA-stimulated healthy donors and MM patients' PBMC. The cellular surface ultrastructure of MM lymphocytes incubated with 100 u/ml IFN showed disappearance of the microvilli and formation of cellular pits, whereas in healthy donor lymphocytes IFN caused flattening of microvilli. PMID- 8484956 TI - Decreased cholesterol biosynthesis in fibroblasts from patients with Parkinson disease. AB - The underlying cause of cellular degeneration in the substantia nigra of patients with Parkinson disease has not been clearly established. With the objective of investigating whether metabolic abnormalities would be detected in peripheral non neuronal cells, we began assessing key metabolic parameters in skin fibroblasts of these patients. The present report focuses on the finding of a remarkably reduced cholesterol biosynthetic capability of fibroblasts from patients with Parkinson disease. 14C-Acetate incorporation into cholesterol of these fibroblasts was 27.8 +/- 9.4% that observed in normal fibroblasts, and the reduced cholesterol synthesis was confirmed by measuring the activity of the rate limiting enzyme HMGCoA reductase which averaged 6.64 +/- 2.50 nmol/h/mg protein in the patient's fibroblasts compared to 14.70 +/- 0.69 nmol/h/mg protein in the control fibroblasts. Cholesterol esterifying activity, as cholesteryl oleate formed from 14C-oleate, of the fibroblasts from Parkinson patients, was reduced by an average 43%. Two hypotheses are put forward to link these findings with the current experimental evidences for both increased lipid peroxidation and defective mitochondrial respiratory chain complex I activity in a number of cell types from Parkinson patients. Considering that decreased cholesterol biosynthesis has been detected in all the Parkinson cell lines thus far investigated, it is suggested that this may be a hallmark of the disease. PMID- 8484957 TI - HIV screening of newborns. AB - Iowa has participated in the national survey for the prevalence of HIV infection in childbearing women since July of 1989. As of February 1992, blinded testing for antibodies to HIV has been performed on blood spot specimens from 100,717 newborns. Of this number, 14 were confirmed as positive by Western blot. In the Iowa survey the prevalence of HIV infection in childbearing women was 0.14/1000 or 1/7000. This is similar to the prevalence that was observed for PKU in newborns during this time period. However, assuming only 30% of mothers transmit HIV to their babies, the predicted prevalence of HIV infection in Iowa newborns is 1/23,000. Certainly HIV disease is a public health concern with a frequency in Iowa mothers similar to that of other diseases screened for in the Iowa program. HIV meets the remaining WHO criteria for newborn screening, as well: the HIV screening test is simple and reliable and has a low incidence of false-positive and false-negative results; confirmatory testing, counseling, and medical care are available; the quality and length of life of affected individuals are improved by treatment; and data show that early diagnosis and treatment result in a cost advantage to society. The major obstacle to the addition of HIV testing to a newborn screening program is obtaining informed consent without jeopardizing program effectiveness. PMID- 8484958 TI - Sandwich enzyme immunoassay for rat retinol-binding protein using antibody against recombinant antigen and its application. AB - The development of a sandwich enzyme immunoassay for rat retinol-binding protein using molecular biological techniques was described. Rat retinol-binding protein gene cloned by the PCR method was expressed by a fusion vector pEZZ18 in Escherichia coli strain HB101. A recombinant retinol-binding protein fused with IgG-binding domain ZZ of protein A was purified with IgG-Sepharose. Antibody against the recombinant protein was found to be specific to rat retinol-binding protein in plasma by immunoblot analysis. Affinity-purified anti-recombinant protein IgG was biotinylated and used for the sandwich enzyme immunoassay. In this assay, the measurable range is 1.9-60 ng/ml and the coefficients of variation within and between the assay series (assay range: 4-30 ng/ml) are 4.30 +/- 4.33 and 5.32 +/- 1.45%, respectively. Cross-reactivity of the immunoassay was examined using bovine, human, and mouse serum. There was a cross-reaction only with mouse serum. In an in vitro experiment, retinol-binding protein produced by rat hepatocytes could be measured by the sandwich enzyme immunoassay. PMID- 8484959 TI - The dual effects of Ca2+ on binding of the glycolytic enzymes, phosphofructokinase and aldolase, to muscle cytoskeleton. AB - We show here that in rat diaphragm muscle, a short time of incubation with the Ca(2+)-ionophore A23187 induced an increase in cytoskeleton-bound phosphofructokinase (EC 2.7.1.11) and aldolase (EC 4.1.2.13), whereas a longer period of incubation, which causes a pathological rise in intracellular Ca2+, induced a decrease in bound enzymes. Lactate concentration correlated with both phases of Ca2+ action on the binding of the enzymes. The increase in cytoskeleton bound enzymes could be prevented by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a novel, potent, and selective inhibitor of calmodulin activity). These results suggest that calmodulin is involved in the Ca(2+)-induced binding of the enzymes to muscle cytoskeleton. PMID- 8484960 TI - Metabolic response to nonglucidic nutrient secretagogues and enzymatic activities in pancreatic islets of adult rats after neonatal streptozotocin administration. AB - In islets from adult rats injected with streptozotocin during the neonatal period, both a nonmetabolized analog of L-leucine and 3-phenylpyruvate augmented 14CO2 output from islets either prelabeled with L-[U-14C]glutamine or exposed to D-[2-14C]glucose and D-[6-14C]glucose, in a manner qualitatively comparable to that found in islets from control rats. The islets of diabetic rats differed, however, from those of control rats by their unresponsiveness to both the L leucine analog and a high concentration of D-glucose in terms of increasing 3HOH generation from [2-3H]glycerol, an impaired sparing action of the hexose upon 14CO2 output from islets prelabeled with [U-14C]palmitate, and, most importantly, by a decreased rate of D-[2-14C]glucose and D-[6-14C]glucose oxidation when either incubated at a high concentration of the hexose (16.7 mM) or stimulated by nonglucidic nutrient secretagogues at a low concentration of D-glucose (2.8 mM). In islet homogenates, the activity of glyceraldehyde phosphate dehydrogenase, glutamate decarboxylase, and NADP-malate dehydrogenase was lower in diabetic than control islets. Such was not the case for glutamate-alanine transaminase, glutamate-aspartate transaminase, or glutamate dehydrogenase. The neonatal injection of streptozotocin thus affected, in the adult rats, the activity of several islet enzymes. Nevertheless, the metabolic data suggest that an impaired circulation in the glycerol phosphate shuttle, as observed in response to stimulation of the islets by either a high concentration of D-glucose or nonglucidic nutrient secretagogues, represents an essential determinant of the preferential impairment of glucose-induced insulin release in this model of non insulin-dependent diabetes. PMID- 8484961 TI - Possible mechanism of interleukin-2-induced decline of serum cholesterol during adoptive cellular immunotherapy in cancer patients. AB - The serum levels of total, LDL, and HDL cholesterol of patients receiving intravenous infusion of interleukin-2 as part of adoptive cellular immunotherapy were analyzed. The total, LDL, and HDL cholesterol significantly decreased to about one-half of the pretreatment levels after 5 days of infusion (183 +/- 34 to 110 +/- 19, 112 +/- 40 to 48 +/- 24, and 41 +/- 10 to 16 +/- 7 mg/dl, respectively). The decrease was gradual during each day of the treatment. Lymphocyte concentration increased markedly during treatment (4.0 +/- 0.52 to 12.3 +/- 2.95 million cells/ml) and the low-density lipoprotein receptor levels in the lymphocytes also increased significantly (1188 +/- 240 to 1442 +/- 276 ng of bound LDL/million cells). The decrease in cholesterol levels may be related to the cholesterol needed for membrane synthesis during lymphocyte proliferation. PMID- 8484962 TI - Complementation analysis of patients with intact peroxisomes and impaired peroxisomal beta-oxidation. AB - Complementation analysis, using peroxisomal beta-oxidation of very long chain fatty acids (VLCFA) as the criterion for complementation, is useful in the study of patients who are suspected of having a single enzyme defect in the peroxisomal beta-oxidation pathway. Laboratory findings for these patients include elevated plasma VLCFA and impaired VLCFA oxidation in fibroblasts. Some of these patients have slightly abnormal phytanic acid oxidation in fibroblasts. In addition, elevated levels of bile acid intermediates have been reported in some cases. Plasmalogen synthesis, pipecolic acid levels, and subcellular distribution of catalase are normal. Using complementation analysis, we show that six patients, who were suspected of having a single enzyme defect in the peroxisomal beta oxidation pathway, are deficient in peroxisomal bifunctional enzyme [enoyl-CoA hydratase (EC 4.2.1.17)/3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35)] activity. This group of six patients, deficient in bifunctional enzyme activity, may be subdivided into two complementation groups. It would appear that patients in each of these two groups are deficient in only one of the bifunctional enzyme activities. PMID- 8484963 TI - Effects of cycloheximide and tunicamycin on lysosomal cystine transport in rat FRTL-5 cells. AB - Rat thyroid FRTL-5 cells were employed to study the synthesis and degradation of a functional integral lysosomal membrane protein, the lysosomal cystine transporter. This carrier exhibited countertransport and closely resembled the cystine transport system of human leucocytes, fibroblasts, and lymphoblasts shown to be defective in the lysosomal storage disease, nephropathic cystinosis. Using cycloheximide to prevent new protein synthesis, the half-life of the FRTL-5 cell lysosomal cystine carrier was determined to approximate 21 h. Carrier function was not influenced by the N-glycosylation inhibitor tunicamycin, nor by the oligosaccharide processing inhibitors castanospermine and deoxymannojirimycin. The data suggest that the lysosomal cystine carrier is a protein without strict functional requirements for N-linked oligosaccharides, and that rat FRTL-5 cells can be employed in future investigations into the structure and function of other integral lysosomal membrane proteins as well. PMID- 8484964 TI - Purification of nonantibiotic insulinase inhibitors from bacitracin. AB - Bacitracin is commonly used in metabolic studies as an insulinase inhibitor. The many isoforms of the commercial preparation were fractionated by charge and size in order to find the most active rat-muscle insulinase inhibitors. CM-Sepharose chromatography revealed that most of the inhibitory activity was contained in a fraction (CM-Inh) that amounted to less than 5% of the mixture. The CM-Inh fraction could be further separated by size on Bio-Gel P4 columns. Six subgroups, each with characteristic specific activity, were isolated. The most potent inhibitor fractions have no antibiotic activity and have molecular weights about twice that of bacitracin A. The peaks isolated by means of Bio-Gel P4 chromatography can be further fractionated by reversed phase HPLC on a C8 column, and by electrophoresis on nonreducing acrylamide gels. PMID- 8484965 TI - Sulfite inhibits oxalate production from glycolate and glyoxylate in vitro and from dichloroacetate infused i.v. into male rats. AB - The effect of sulfite on oxalate production from glycolate and glyoxylate was investigated in an in vitro assay system using rabbit muscle LDH and rat liver 35 60% ammonium sulfate fraction as enzymes. A > or = 50% inhibition in oxalate production was observed at sulfite to glyoxylate ratio of 0.4. LDH activity (change in A340 nm) was inhibited by > or = 40% at sulfite to glyoxylate ratio of 0.5. Male Sprague-Dawley rats fasted for 24 h and infused with dichloroacetate (150 mg/rat/h, iv, n = 6), without and with sodium sulfite (150 mg/rat/h, n = 6) excreted oxalate in urine, respectively, at the rate of 1.13 +/- 0.29 and 0.61 +/ 0.09 mumol/h/100 g body wt, showing a nearly 50% reduction due to sulfite. The present report demands further experimentation to define the role of sulfite as an intracellular modulator of oxalate production. PMID- 8484966 TI - Characterization of the response of erythrocyte sodium-lithium countertransport to inhibitors. AB - To clarify the biochemical characteristics of the sodium-lithium countertransporter (SLC) the responses of SLC to two probes of ion transport- 4,4'-diisothiocyanostilbene-2,2' disulfonate, and N-ethylmaleimide--were assessed. The results suggest that the SLC transporter is associated with the band 3 protein in the plasma membrane and demonstrate that a sulfhydryl group is essential for transport function. PMID- 8484967 TI - Axillary surgery in breast cancer--there still is a debate. PMID- 8484968 TI - Neuroblastoma: a multiple biological disease. AB - Neuroblastoma (NB) is a paediatric tumour showing an appreciable variability in clinical evolution. Localised tumours (especially stage 1) can be mildly treated with good success while metastatic tumours (stage 4) are highly aggressive. This suggests a great biological diversity. In fact, molecular and genetic studies have revealed distinct abnormalities in localised and non-localised tumours. Loss of heterozygosity for the short arm of chromosome 1, 1p deletion, and MYCN amplification are present in stages 3 and 4 but rarely in stages 1 and 2. Metastatic stage 4S in infants is peculiar and does not show the same genetic and molecular abnormalities found in advanced metastatic tumours. Considering the biological alterations associated with NB, it would appear that advanced stage NB conforms to the multistep model of tumour development while stage 4S can be divided into two groups: one arising from a lack of cellular differentiation and the other as a consequence of an additional 'one hit' mutation. PMID- 8484969 TI - Histopathological grade and response to chemotherapy in advanced soft tissue sarcomas. AB - In a retrospective analysis, we evaluated the possible significance of histopathological grade with regard to response to chemotherapy in advanced soft tissue sarcomas. In three EORTC protocols, the same dose-schedule was used for patients randomised to treatment with doxorubicin as a single agent (75 mg/m2 every third week). The submitted pathological slides from 94 of these patients were reviewed and graded. The following parameters were subjectively graded (+/++/+ + +): nuclear pleomorphism, necrosis, cellularity and vascularity. Mitoses were counted in 20 high-power fields, and a final grade assigned as I, II, IIIA or IIIB. The results were tested both with regard to response (complete response + partial response vs. no change + progressive disease) and survival. However, no statistically significant correlations or trends could be demonstrated. Thus, tumour grade, although a prognostic factor by itself, does not seem to be able to predict response to chemotherapy in the advanced stage. PMID- 8484970 TI - The effect of danazol on tumour control and weight loss in patients on tamoxifen therapy for advanced breast cancer: a randomised double-blind placebo controlled trial. AB - To assess the effect of danazol in advanced breast cancer 183 patients were randomised to receive either tamoxifen plus danazol or tamoxifen plus placebo. Patients underwent systemic work-up pretreatment then every 12 weeks or sooner if they clinically progressed. There were no differences in objective response rates with tamoxifen plus danazol vs. tamoxifen plus placebo (27% vs. 24%), time to progression (median 6.4 vs. 6.2 months) or survival (median 22.6 vs. 23.5 months) when the two arms were compared (all P > 0.5). The addition of danazol to tamoxifen had no effect on time to progression when adjusted for significant prognostic factors in a multivariate analysis. However, it was found incidentally that weight was stable on tamoxifen plus danazol (average gain 0.6 kg, S.E. 0.6 kg) compared with a significant loss on tamoxifen plus placebo (average loss 2.0 kg, S.E. 0.6 kg, P = 0.003). The average weight was maintained on tamoxifen plus danazol even in patients who did not respond to treatment. PMID- 8484971 TI - Long-term effects of cancer treatment and consequences of cure: cancer survivors enjoy quality of life similar to their neighbours. AB - To assess the long-term effects of cancer treatment and consequences of cure, 102 index cancer cases were compared with 95 neighbourhood controls of similar age and sex and with 78 cardiac controls. The quality of life experienced by these three groups was examined using multiple instruments with proven psychometric properties. All the major quality of life domains (physical, psychological and social) were covered. The findings revealed that the index cases were similar to their neighbours in areas of subjective well-being. However, the index cases exhibited more sexual dysfunction, were more conscientious, determined and emotionally disciplined, and applied the defence mechanisms of displacement and reaction formation more often than the neighbourhood controls. The cardiac controls were older, more anxious, more conventional/less imaginative and used suppression as a defence mechanism to a greater degree than the index cases. In conclusion, young adult cancer survivors enjoy a quality of life similar to their neighbours, whereas coronary bypass survivors adjust less well psychosocially. PMID- 8484972 TI - Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group. AB - Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN. PMID- 8484973 TI - Lipid-bound sialic acid, prostaglandin E and histamine in head and neck cancer. AB - Blood concentration of lipid-bound sialic acid (LBSA), prostaglandin E (PGE) and histamine were determined in 37 patients with carcinoma of hypopharynx and larynx (supraglottic and glottic), in 12 non-cancer patients and in 10 healthy subjects. The concentration of LBSA was significantly increased in 94.4% cancer patients preoperatively and fell to somewhat lower levels within 1 month after tumour resection. In patients with complete tumour resection and no tumour recurrences within 2 years, it steadily decreased thereafter, reaching normal levels within 6 24 months after surgery, whereas in patients with tumour recurrences or incomplete tumour resection it rose again within 6 months after tumour resection. Similarly, the concentration of PGE was significantly increased in about two thirds of cancer patients (67.6%) preoperatively, dropped significantly within 1 month after tumour resection and rose again in patients with tumour recurrences. Preoperative histamine concentration was decreased in 24.3% of cancer patients and postoperatively it rose both in patients with or without tumour recurrences. PMID- 8484974 TI - A prognostic score for patients resected for gastric cancer. AB - This paper describes the construction, validation and use of a simple prognostic score suitable for predicting survival of patients undergoing a curative gastric resection. Using death from all causes as outcome, the prognostic significance of age, sex, tumour site, stage of disease (nodal status and wall invasion), surgical treatment and histological type was investigated in a set of 213 patients recruited in a multi-centre clinical trial. A Weibull multiple regression model was adopted to evaluate the joint effect of these variables on survival. From a full model, containing all the variables, a final parsimonious model was obtained by means of a backward selection procedure. The prognostic score is based on the final model, including four variables which are easily detected in every institution: age, wall invasion, site of tumour, and nodal status. Three groups of patients with different probabilities of surviving 5 years from surgery were identified: group I (survival probability > or = 70%), group II (30%-69%) and group III (< 30%). The prognostic score, obtained from the multicentre trial patients, was tested on a set of 135 consecutive patients in an independent institution, confirming its reliability in predicting survival. The score system presented can supply a simple tool for classifying patients radically operated for gastric cancer into three well discriminated groups from the prognostic point of view. PMID- 8484975 TI - First-line combination chemotherapy with mitoxantrone, methotrexate, vincristine and carboplatin (MIMOC) in advanced breast cancer. AB - 51 patients with stage IIIB and IV breast cancer entered a prospective phase II study of combination chemotherapy that consisted of mitoxantrone (8 mg/m2) day 1, methotrexate (25 mg/m2) day 1, vincristine (1 mg/m2) day 2 and carboplatin (250 mg/m2) day 2 (MIMOC) given in a 3-weekly schedule. None had received prior chemotherapy for metastatic disease, although 16 patients were given adjuvant chemotherapy. Objective response to treatment was seen in 29 of 48 patients analysed for response (60%) with 8 complete responses (CR). 7 out of 8 patients with stage IIIB disease responded, 2 of them completely. Responses were seen in all sites but the best results were achieved in lung metastases with 50% CR. The median duration of response was 8 months and the median time to disease progression was 12 months. The main toxicity was nausea and vomiting which was severe in 20% of the patients. Other toxicities were mild. MIMOC was administered on an out-patient basis and appears to be effective as first-line treatment in advanced breast cancer. PMID- 8484976 TI - Prevention of emesis by ICS 205-930 in children receiving cytotoxic chemotherapy. AB - Nausea and vomiting are among the most frequent and severe acute side-effects of cytotoxic therapy and are not optimally controlled by conventional antiemetics. This situation warrants the evaluation of new classes of antiemetic agents such as the 5-HT3 receptor antagonists. 19 children with a median age of 9 years (range 2-16 years), treated with cytotoxic drug combinations that had previously caused nausea and vomiting refractory to conventional antiemetics, were given the selective 5-HT3 receptor antagonist ICS 205-930. The drug was given intravenously (i.v.) at 0.2 mg/kg (maximum 5 mg) during the chemotherapy infusion period and was continued orally for up to 5 days in chemotherapy courses containing cisplatin. The number of emetic episodes was recorded and the response was scored according to following scale: grade 1 = no nausea, no emetic episode; grade 2 = up to four episodes of vomiting and less than 5 h of nausea; grade 3 = five or more than five emetic episodes and/or nausea for at least 5 h. The 19 patients received a total of 169 various courses of chemotherapy combined with ICS 205 930. A score of 3 was observed during one course only, a score of 2 in 37 out of the 169 courses, including the four courses with cisplatin. The drug was very well tolerated. Side-effects possibly related to ICS 205-930 were mild to moderate headache in 4 patients during seven courses overall and obstipation in 3 patients during 11 courses. The results strongly suggest that ICS 205-930 is a highly effective and safe antiemetic agent in non-naive pediatric patients receiving non-cisplatin cytotoxic chemotherapy and who had failed conventional antiemetic treatment. PMID- 8484977 TI - Phase II study of elliptinium acetate salvage treatment of advanced breast cancer. AB - Elliptinium acetate (Celiptium) is an intercalating agent belonging to the ellipticine family. This agent has demonstrated clinical activity as salvage treatment in breast cancer using a weekly regimen. However, its clinical use was hampered by important toxicities such as xerostomia and immune-mediated haemolytic reactions due to development of anti-elliptinium IgM antibodies. We have studied 83 patients previously treated for metastatic breast cancer using elliptinium acetate with a different schedule: 80 mg/m2 daily for 3 consecutive days every 21 days. In 80 evaluable patients, an objective response (complete + partial response) was obtained in 5 of 30 patients with visceral metastases (13%), in 6 of 21 patients with soft tissue metastases (29%), and in 3 of 20 patients with mixed metastases (15%). The overall objective response rate was 14/80 (18%, 95% confidence interval = 10-26%). Moderate to severe xerostomia occurred in 10% of patients, while no anti-elliptinium antibodies or haemolytic reactions were detected using this schedule. No significant haematological toxicity, as usually reported with this drug, was observed. Elliptinium acetate has modest but definite activity as salvage treatment of breast cancer. The 3 week schedule seems as active as and less toxic than the weekly schedule. PMID- 8484978 TI - Psychological reactions in public melanoma screening. AB - Participants in public screening for malignant melanoma (n = 190) completed a questionnaire containing items regarding cognitive and emotional responses to skin examination on two occasions, before screening and 7 months later. The results suggest subjective susceptibility to melanoma in participants in public screening, especially in women. No increase in psychosomatic problems, anxiety or depressive symptoms or signs of "false security" were seen as an effect of the screening, neither in the total sample nor in those who at the screening were recommended further medical procedures. PMID- 8484979 TI - Oral tegafur in the treatment of metastatic breast cancer: a phase II study. AB - Between February 1985 and October 1989, 26 patients previously treated for metastatic breast cancer received oral tegafur, at a median daily dose of 1200 mg. Of these, 21 were evaluable for response. The overall response rate was 29%; six (two in lungs, two in skin and two in lymph nodes) of 44 evaluable lesions (14%) responded to therapy. Haematological toxicity was mild, and no other dose limiting toxicity was seen. The data indicate some activity in heavily pretreated metastatic breast cancer even after previous 5-FU therapy. PMID- 8484980 TI - Prevalence of anticipatory nausea and other side-effects in cancer patients receiving chemotherapy. AB - 98 patients receiving chemotherapy for cancer were interviewed to determine the prevalence of anticipatory nausea and vomiting, anxiety and dietary changes. Among those who had received at least four treatments 41% reported at least mild anticipatory nausea (AN). For 24% this was a moderate to severe problem, which was significantly associated with a high level of anxiety about treatment. Prevalence at this level was independent of whether the subject was receiving treatment as an in- or an outpatient. Anticipatory vomiting (AV) was reported by only 12 patients, of whom 11 were women; this was the only effect of gender found in the sample. Independence between moderate AN and AV was also suggested by a difference in type of event triggering the effect: predominantly odours for AN and thoughts of the treatment for AV. Changes in diet after commencing chemotherapy were reported by 50% of patients who had received at least four treatments. These most commonly took the form of aversions to meat and then to coffee, and were attributed most frequently to changes in taste and then to loss of appetite. PMID- 8484981 TI - Correlation between changes in the tumour markers CA-M26 and CA-M29 and standard response evaluation in patients with metastatic breast cancer. AB - In this study we correlated response evaluated by standard WHO criteria to strict defined criteria of tumour marker response in 63 patients with metastatic breast cancer. Pretreatment sensitivity at first evaluation was 71% and 85% for CA-M26 and CA-M29, respectively. Of the 156 evaluations for CA-M26 and 178 for CA-M29 in 26 and 30 patients with evaluable lesions 72% and 67% were concordant with the results of the clinical evaluations. When the discordant evaluations due to lead time were included the concordances were 87% for CA-M26 and 83% for CA-M29. Of the 70 evaluations for CA-M26 and 92 for CA-M29 in 19 and 24 patients with non evaluable lesions 59% and 72% were concordant with the results of the clinical evaluations. Most importantly, progressive disease according to the changes in the marker level nearly always predicted disease progression. Such knowledge obtained in a simple way may prevent continuation of ineffective treatment in patients with metastatic breast cancer. PMID- 8484982 TI - Trends and survival in AIDS-associated malignancies. AB - Data from 1569 AIDS cases reported to the population-based AIDS Registry of Catalonia have been analysed to describe the epidemiology and temporal evolution of both Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL). Of the 1569 cases reported, 53 (3.4%) presented with NHL and 135 (8.6%) with KS. KS cases were more frequent among homosexual/bisexual men and the age of KS cases was significantly higher than all others presenting diseases (38.22 years). NHL cases were more frequently among men but no significant age difference was found. The percentage of KS over time decreased significantly only among intravenous drug users. Cases presenting with a NHL had by far the worst prognosis (median survival time = 169 days). Biases affecting the measurement of AIDS associated malignancies (AAM) using surveillance data are analysed. The prevalence of AAM will increase during the next few years, and NHL may be one of the leading causes of death among AIDS patients in the near future. PMID- 8484983 TI - Immunochemical analysis of the p53 oncoprotein in matched primary and metastatic human tumours. AB - There is much interest in the range of genetic aberrations which occur in human malignancies. An immunohistochemical study has been carried out to investigate the consistency of expression of abnormally accumulated p53 protein in paired samples of archival primary and metastatic carcinomas. The staining of methacarn fixed tissue from 136 matched pairs of mammary carcinoma and 20 cancers from other sites was completed using antibody CM-1 and DO1 in a sensitive peroxidase conjugated streptavidin-biotin technique. The majority of tumour cells were positive in 25% and the tumours were negative in 17% of the primary carcinomas; staining was heterogeneous in the remaining cases. Staining was identical in 180/186 (96%) metastatic lesions. An ELISA assay carried out on 12 matched pairs of the tumour specimens demonstrated that altered conformation of the aberrant p53 protein present in a primary lesion was maintained in its metastasis. These data indicate that alterations in the p53 gene result in a relatively stable phenotype and that progression of disease is not usually accompanied by either further mutation or loss of the mutant allele. PMID- 8484984 TI - EO9: a novel bioreductive alkylating indoloquinone with preferential solid tumour activity and lack of bone marrow toxicity in preclinical models. AB - EO9 is a novel and fully synthetic bioreductive alkylating indoloquinone. Although structurally-related to mitomycin C, EO9 exhibits a distinct preclinical antitumour profile and there are also differences in its biochemical activation. In this study, EO9 was found to demonstrate preferential cytotoxicity against solid tumours in vitro as compared to leukaemia cell lines both in the Corbett two-tumour assay and in the disease-oriented human tumour cell line panel of the U.S. National Cancer Institute. In the latter system activity was particularly apparent in colon, melanoma and central nervous system lines, together with some renal and non-small cell lung lines. Preferential cytotoxicity towards hypoxic versus aerobic EMT6 mouse mammary tumour cells was observed. In vivo, EO9 was inactive against the P388 murine leukaemia, while exerting significant antiproliferative effects against several murine and human solid tumours, including the generally resistant MAC mouse colon tumours and gastric, ovarian and breast xenografts. These results confirmed in vitro observations of preferential solid tumour activity. In animal toxicology studies, EO9 induced vascular congestion in the gastrointestinal tract, but no significant bone marrow toxicity. The LD10 value of EO9 after a single intravenous injection into mice was 9 mg/kg (27 mg/m2). A dose of one-tenth of the mouse equivalent LD10 (2.7 mg/m2), the recommended starting dose for clinical phase I studies, was found to be safe in rats. Considering its distinct mechanism of bioactivation as compared to mitomycin C, its preferential solid tumour activity, its excellent activity against hypoxic cells, and lack of significant bone marrow toxicity in animals studies, EO9 has been selected for clinical evaluation within the framework of the EORTC. PMID- 8484985 TI - Towards an international register of cancer trials: the UKCCCR register of U.K. trials. PMID- 8484986 TI - Axillary surgery in breast cancer: what debate? PMID- 8484987 TI - Side-effects of GM-CSF treatment in advanced testicular cancer. PMID- 8484988 TI - Hodgkin's disease as pyrexia of unknown origin in a patient with chronic lymphocytic leukaemia. PMID- 8484989 TI - The prophylactic use of fluconazole 50 vs. 100 mg daily in haematological malignancies. PMID- 8484990 TI - Response of soluble IL-2 receptor levels to repeated cycles of IL-2 immunotherapy/chemotherapy. PMID- 8484991 TI - Is kidney the real dose-limiting organ after total body irradiation and bone marrow transplantation? PMID- 8484992 TI - Mike Grace talks to Norman Whitehouse. PMID- 8484993 TI - 'A study of the quality of impressions for anterior crowns received at a commercial laboratory'. PMID- 8484994 TI - A study of the quality of impressions for anterior crowns received at a commercial laboratory. PMID- 8484995 TI - 'G.A. for tooth extraction for children in London'. PMID- 8484996 TI - 'Current classifications of HIV-associated periodontal disease'. PMID- 8484997 TI - Current classifications of HIV-associated periodontal disease. PMID- 8484998 TI - Orthodontics in the general dental service of England and Wales: a critical assessment of standards. AB - Out of a sample of 1210 orthodontic patients treated within the General Dental Services in England and Wales, a high proportion showed no improvement. Upper and lower fixed appliances had the greatest influence on the outcome of treatment in terms of aesthetics, dental health need and standards. When treatment was analysed according to the appliance used, there were no statistically significant differences in the standard of treatment undertaken by specialist orthodontists and general dental practitioners. Methods for improving British orthodontic standards are considered. PMID- 8484999 TI - Rubber dam usage related to restoration quality and survival. AB - The effects of rubber dam or cotton roll isolation on the initial quality and later survival of 644 amalgam and 149 anterior enamel-bonded composite resin restorations were evaluated over periods of up to 15 and 10 years, respectively. All restorations were placed by one operator and their quality assessed at the time of finishing, using seven clinical characteristics. The influence of six other clinical parameters on the survival of the restorations was also evaluated. There were no clinically-significant differences present in the initial high quality of the restorations, or in their later survivals, which could be directly related to the use or otherwise of rubber dam. Overall, the restoration survivals were excellent. However, there were significantly more amalgam restoration failures, from bulk fracture, in patients with severe bruxism. PMID- 8485000 TI - Transient uniocular blindness after dental extraction under general anaesthetic. AB - A 14-year-old boy suffered transient uniocular blindness after extraction of four permanent first molar teeth under general anaesthetic. We discuss the theoretical basis for ocular vasospasm secondary to the minor trauma of dental extraction being relayed to the orbit. PMID- 8485001 TI - Images of your future. AB - Would you buy something without seeing it first, and without any real idea of what it was you were buying, or whether you really wanted it? In the past, that is what dental patients have been expected to do when their dentist has offered them restorative dentistry, but now, using a dental imager, you can show your patients quickly and simply just what you can do to improve their appearance; and they can show you exactly what it is they want. PMID- 8485002 TI - A turn up for the books? AB - They say that waiting is the worst part but if it is true for patients it is just as true for dentists. The missed appointment, or the appointment cancelled leaves us waiting. It is wasteful and expensive but more than either of these economic irritations it is straight forwardly frustrating. PMID- 8485003 TI - [Spontaneous bacterial peritonitis during liver cirrhosis: the clinical findings and therapeutic considerations]. AB - Among 1211 consecutive patients admitted to hospital for liver cirrhosis, 625 (51.6%) had ascites. Forty-four of them (7%) had ascitic infection. Thirty-four cases (5.4%) of spontaneous bacterial peritonitis (SBP) and 10 cases (1.6%) of culture-negative neutrocytic ascites (CNNA) were diagnosed. The infecting organism was most likely Gram-negative of enteric origin (80%), CNNA mortality (30%) was lower than that of SBP (47%). High mortality suggests to treat patients affected by either SBP or CNNA with antibiotics. PMID- 8485004 TI - Effect of plasma exchange in a patient with prolonged deep coma from thrombotic thrombocytopenic purpura. AB - The clinical, laboratory and instrumental data of a patient with thrombotic thrombocytopenic purpura (TTP) are reported in detail, with reference to an articulated therapeutic regimen including plasma exchange, high-dose methylprednisolone and dipiridamole. Particular emphasis is placed on the dramatic improvement obtained with this treatment despite a very delayed diagnosis and prolonged, severe neurological involvement. A short discussion and review of the literature concerning the role of plasma-exchange in the treatment of TTP is reported. PMID- 8485005 TI - Complete regression of iatrogenic Kaposi's sarcoma due to corticosteroid treatment in a patient with tubercular pericarditis. A case report. AB - We report a case of drug-induced Kaposi's sarcoma (KS) on the sole of the right foot in a 71-year-old man, treated for 6 months with corticosteroid therapy (prednisolone 25 mg/day) for pericardial effusion. After corticosteroid withdrawal, a tuberculin skin test became strongly positive and pericardial effusion was considered to be of tubercular origin. The patient remained constantly HIV negative during 14 months of follow-up. Seven months after continuous antitubercular treatment, the KS nodules regressed spontaneously and finally disappeared. Histological studies confirmed the diagnosis of KS and documented its complete regression. Laboratory investigation confirmed prior exposure to CMV, EBV and HSV and suggested drug-induced immunological suppression. Analysis of the HLA system revealed the positivity of locus DR5, associated with classical KS. This case report underscores the relationship between genetic background, environmental factors, drug-induced immunosuppression and the evolution of this peculiar neoplasm. PMID- 8485006 TI - [Necrotizing lymphadenitis (Kikuchi's disease) and systemic lupus erythematosus: a single entity?]. AB - Kikuchi's necrotizing lymphadenitis is a histologically alarming but self limiting lesion typically affecting the cervical lymph nodes of young women. The authors report 2 cases of systemic lupus erythematosus with the finding of Kikuchi's disease on lymph node biopsy. Considering the common infectious and/or immunologic etiologies described in both disorders, coexistence of both conditions suggests the possibility that they share a common etiology. PMID- 8485007 TI - Hematological changes in infectious diseases. Hematological consequences of bacterial, protozoal and spirochetal infections (2). AB - A number of distinct hematological alterations take place in the presence of infectious diseases. This review seeks to provide a diagnostic guide and prognostic criteria for the clinician in the light of the concomitant hematological changes occurring in course of acute and chronic viral, bacterial, spirochetal and protozoal infections. The authors emphasize the fact that although certain broad principles may be applied to each type of infection, these principles may have to be interpreted with considerable latitude in any individual case, on account of the variable factors of virulence and resistance. The careful examination of blood films and bone marrow smears, supplemented when appropriate by cytochemical reactions, may be useful in the differential diagnosis of various infective states and in assessing both the severity of the pathological condition and the response of the patient. PMID- 8485008 TI - [Risk factors for the progression of chronic kidney failure]. AB - Virtually all renal diseases progress, although at different rates, to end-stage renal failure. The main clinical factors which may explain such relentless progression are reviewed and include: the underlying renal pathology, with the most rapid progression rate observed in glomerular disease and in polycystic kidney disease; systemic hypertension, a significant risk factor for progression in any renal disease; the magnitude and duration of proteinuria with the fastest progression rate found in the nephrotic syndrome; the degree of functional renal deterioration at which so called conservative treatment is prescribed. The proper identification of these risk factors may result in rational dietary and non dietary intervention with the aim of slowing the progression of chronic renal disease. PMID- 8485009 TI - Refractory ascites: definition, pathogenesis and treatment. AB - Refractory ascites, that is ascites which cannot be mobilized by low sodium diet and maximal doses of diuretics (up to 400 mg spironolactone or potassium canrenoate and 160 mg furosemide per day), occurs in 5% of cirrhotic patients with ascites. The development of refractory ascites is mainly related to the progression of arterial vasodilation-mediated vascular underfilling and to the imbalance between reduced synthesis of renal vasodilating factors (especially renal prostaglandins) and extreme activation of vasoconstricting systems. Further features include increased sodium reabsorption in the proximal tubule and altered pharmacokinetics and pharmacodynamics of diuretics. In patients with impaired renal function (as is the case for most patients with refractory ascites), the marked reduction of renal perfusion and glomerular filtration rate, with the consequent decrease of filtered sodium load, becomes the main pathogenetic factor. The principal therapeutic options for refractory ascites include repeated paracentesis and implantation of the LeVeen shunt. Paracentesis is a rapid and safe procedure to remove ascites, but it does not correct sodium retention. Ascites recurrence, therefore, may occur after a brief interval. The LeVeen shunt allows for better long-term control of ascites, but severe complications may supervene, and shunt occlusion is common. Neither therapeutic procedure improves survival. Different experimental therapeutic procedures have been proposed. Administration of ornipressin corrects hyperdynamic circulation and improves renal function. Thromboxane synthase inhibitors, by reducing renal synthesis of thromboxane A2, potentiate the diuretic and natriuretic response to furosemide. More invasive procedures, including portosystemic shunt and transjugular intrahepatic stent, are rarely used in the treatment of refractory ascites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485010 TI - The case of primary systemic amyloidosis in chronic diarrhea, weight loss and hypotension. PMID- 8485011 TI - The clinical spectrum of the immunocompromised host: a pathology engineered by progress. AB - The term "immunocompromised host" (ICH) embraces patients with a remarkably heterogeneous array of disease forms whose common feature is an immunologic deficiency of varying gravity and extent. From the clinical standpoint, too, they display a heterogeneous spectrum, ranging from virtually symptom-free pictures through all the intermediate stages to the appearance of typical manifestations including: a) high susceptibility to recurrent infection by opportunistic germs; b) frequent though not always clinically significant autoimmune phenomena; c) the occasional appearance of some tumors (mostly Kaposi's sarcoma and hemolymphopoietic system neoplasias), also referred to as "opportunistic" by analogy with opportunistic infections. The existence of a variety of modern treatments (organ and bone marrow transplantation, aggressive combination chemotherapy and/or radiotherapy of tumors, prolonged administration of immunodepressants in a number of immune-mediated disease conditions, etc.) that prolong survival in patients with chronic immunodeficiency states previously responsible for early death has led to a new "pathology engineered by progress". PMID- 8485012 TI - The role of clinical pharmacology in the development and assessment of drugs for cerebrovascular disease and stroke. PMID- 8485013 TI - Non-steroidal anti-inflammatory drugs and angiotensin converting enzyme inhibitors: a commonly prescribed combination with variable effects on renal function. PMID- 8485014 TI - Disagreement between standard transthoracic impedance cardiography and the automated transthoracic electrical bioimpedance method in estimating the cardiovascular responses to phenylephrine and isoprenaline in healthy man. AB - 1. Impedance cardiography is a well-established noninvasive method to assess within-subject changes of cardiovascular function. We compared the standard approach (ZCG) which requires tedious signal analysis with an automated approach (TEB: NCCOM 3) with its own specific equipment, algorithms and equations in order to assess agreement of the method-specific measurements and calculations. 2. Ten healthy men were studied on two occasions with either ZCG or TEB, at rest and at the end of 5 min i.v.-infusions with 1 microgram min-1 isoprenaline and 100 micrograms min-1 phenylephrine. 3. There was good agreement for the method independent changes (HR, SBP/DBP), but there were large differences for method specific measurements: dZ/dtmax [TEB-ZCG] = -0.68, CI: -0.83 to -0.53 ohm s-1, PEP [TEB-ZCG] = -22.1, CI: -35.0 to -9.2 ms and QS2c [TEB-ZCG] = -16.5, CI: -32.4 to -0.6 ms and for the calculated stroke volume SV [TEB-ZCG] = 30.3, CI: 15.5 to 45.2 ml. The responses of dZ/dtmax and SV to isoprenaline and phenylephrine, although qualitatively similar, reached no quantitative agreement either. A substantial disagreement was evident for the STI responses to isoprenaline where TEB failed to detect the expected reduction of VETc and thus grossly underestimated the shortening of QS2c. 4. It is concluded that TEB-measurements and -calculations did not agree with standard ZCG, that the methods, albeit related, cannot be considered as interchangeable and that suspicion is justified that TEB might yield erroneous results under specific circumstances. PMID- 8485015 TI - Responsiveness of human isolated bronchial segments and its relationship to epithelial loss. AB - 1. The responsiveness of human and bovine bronchi was examined by comparing the magnitude of responses to agonists applied to the adventitial (outside) and to the luminal (inside) surfaces. The development of smooth muscle tone was measured as both an increase in pressure in isovolumic bronchial segments and narrowing in perfused segments. 2. In both closed and perfused human segments, ACh added to the adventitial surface produced highly homogeneous responses while responses to ACh added to the luminal side were extremely variable. 3. Histological examination of the human segments showed that they possessed variable degrees of pre-existing epithelial loss from the mucosal circumference, ranging from 0 to 82%. 4. Denuded human isovolumic segments (exhibiting > 30% epithelial loss) were 40 fold more sensitive to ACh inside than intact segments (< 30%). Denuded segments were also equally responsive to KCl inside or outside while KCl inside produced a contraction that was 50% of that to KCl outside in intact segments. 5. A strong and highly significant relationship was determined between the proportion of epithelial loss and both the responsiveness and rate of contraction of human segments to ACh and KCl introduced onto the lumen. No relationship was observed between epithelial denudation and responsiveness or contractility to agonists added to the adventitial surface. 6. Mechanical denudation of the epithelium from bovine segments had no effect on responsiveness to ACh or KCl added to the outside while significantly augmenting the sensitivity to ACh (9 fold) and reactivity to KCl introduced into the lumen to the extent that it became the same as outside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485016 TI - Partial mediation by nitric oxide of the relaxation of human isolated detrusor strips in response to electrical field stimulation. AB - 1. A method for reproducing relaxation of human isolated detrusor smooth muscle in vitro in response to electrical field stimulation is described. 2. The parameters of stimulation associated with relaxation were those which would be expected to give a largely nerve-mediated response: the relaxations were not reduced by tetrodotoxin (3 x 10(-7) M) and were therefore not dependent on voltage sensitive sodium channels. 3. The relaxations were decreased (mean 74.1%) by nitro L-arginine (NOARG, 10(-5) M). 4. Methylene blue (10(-5) M), an inhibitor of soluble guanylate cyclase, abolished the relaxations. 5. These results indicate that there may be a relaxation mechanism in the human bladder which is at least partly mediated via the production of nitric oxide. PMID- 8485017 TI - A comparison of the potassium and magnesium-sparing properties of amiloride and spironolactone in diuretic-treated normal subjects. AB - 1. The relative potencies of amiloride (5 and 20 mg) and spironolactone (25 and 100 mg) for plasma and erythrocyte electrolytes were investigated in a double blind, randomised, balanced, crossover study in 12 normal men treated concomitantly with hydrochlorothiazide 100 mg daily for 1 week. 2. Participants satisfied an a priori requirement for a fall in plasma potassium concentration of at least 0.5 mmol l-1 after 7 days of treatment with hydrochlorothiazide alone. 3. After hydrochlorothiazide alone, plasma potassium and sodium concentrations fell (P < 0.001). There were associated reductions in erythrocyte sodium (P < 0.01). Plasma magnesium concentration did not change, although erythrocyte magnesium decreased (P < 0.001). 4. Both amiloride and spironolactone attenuated the thiazide-induced fall in plasma potassium (relative potency, amiloride:spironolactone 10:1, 95% confidence interval 6.3-16.2:1). Amiloride but not spironolactone was associated with a dose-related increase in plasma magnesium; a relative potency estimation was precluded. There was little evidence of influences of amiloride or spironolactone on erythrocyte electrolytes. 5. On a weight basis, amiloride is ten times more potent than spironolactone as a potassium-sparing agent in diuretic-treated subjects but neither agent had major effects on erythrocyte potassium. The drugs may have divergent actions on magnesium handling; hydrochlorothiazide alone had no influence on plasma magnesium. PMID- 8485018 TI - Defining small differences in efficacy between anti-parkinsonian agents using gait analysis: a comparison of two controlled release formulations of levodopa/decarboxylase inhibitor. AB - 1. Stride length is highly relevant to mobility and is sensitive to the effects of levodopa in Parkinsonism. Its selection as the primary outcome criterion allowed comparison of two levodopa/decarboxylase inhibitor formulations using a small number of subjects. 2. It is also desirable to improve stability. An instrumental method, based on infrared telemetry, has been developed which obtains both distance/time measures of gait and broadness of base, as measured by foot separation at mid-swing. The latter was used as a subsidiary outcome criterion. 3. Nine patients (aged 57 to 77 years) then receiving maintenance therapy for idiopathic Parkinsonism with Sinemet CR alone, but who had previously experienced end of dose effect within 4 h of receiving a dose of a conventional formulation of levodopa/decarboxylase inhibitor, were studied. 4. They received, in random order and at least 4 days apart, single doses of one tablet of Sinemet CR (200 mg levodopa/50 mg carbidopa) and of two capsules of Madopar CR (each 100 mg levodopa/25 mg benserazide), with placebo balance, at 10.00 h. Gait analysis was carried out immediately before and half-hourly for 7 h after a challenge. No routine doses of Sinemet CR were taken between 22.00 h on the night before and 17.00 h on the day of a challenge. 5. Analysis of variance showed a highly significant difference in mean stride length (P < 0.001) and in mean foot separation (P = 0.01) between serial time points, irrespective of the nature of treatment. There appeared to be a useful therapeutic response to both challenges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485019 TI - The effects of BRL 46470A, a novel 5-HT3 receptor antagonist, and lorazepam on psychometric performance and the EEG. AB - 1. The effects of single doses of a novel 5-HT3 receptor antagonist, BRL 46470A (0.1 microgram, 0.01 mg, 1 mg or 50 mg) and lorazepam (2.5 mg) on psychometric performance and the EEG were investigated in a randomised, double-blind, crossover, placebo controlled study of 16 healthy male volunteers. 2. There was strong evidence that lorazepam had a marked effect on the EEG, increasing power in the 1 Hz to 7 Hz and 13 Hz to 20 Hz wavebands, whilst reducing power in the 8 Hz to 12 Hz waveband. Lorazepam also produced an impairment of daytime function as assessed by psychometric performance and subjective measures. 3. In contrast, there was little evidence to suggest that BRL 46470A had any effect on the EEG or that it impaired daytime function. PMID- 8485020 TI - The pharmacokinetics of methotrexate and its 7-hydroxy metabolite in patients with rheumatoid arthritis. AB - 1. The pharmacokinetics of MTX and its 7-hydroxy metabolite (7-OHMTX) were investigated in nine patients with rheumatoid arthritis (RA). Each patient received 15 mg MTX i.v., i.m. and p.o. after an overnight fast in a randomized cross-over design. The plasma concentrations of MTX and 7-OHMTX were measured over 7 days and their urinary excretion over 24 h. 2. Plasma concentrations of MTX were described by a triexponential function after i.v. administration, a triexponential function with zero or first order absorption after oral administration, and a biexponential function with zero of first order absorption after i.m. injection. Plasma concentrations of 7-OHMTX were described by a biexponential function after all three routes of administration. The median terminal elimination half-lives of MTX and 7-OHMTX were 55 h and 116 h, respectively. The area under the plasma concentration-time curve (AUC (0,170 h)) of MTX did not differ between i.m. and oral administration indicating similar bioavailability after these routes of administration. The AUC (0,170 h) values of 7-OHMTX after i.v., oral and i.m. administration were similar. Over 80% of MTX was excreted in urine as intact drug and about 3% was excreted as 7-OHMTX during 24 h after drug administration. 3. Plasma concentrations of MTX and 7-OHMTX were measurable at the end of the dose interval in most of the patients and may help to identify non-responders or patients with increased risk of side-effects. PMID- 8485021 TI - Stereoselective sulphate conjugation of salbutamol in humans: comparison of hepatic, intestinal and platelet activity. AB - 1. The oral bioavailability of the beta 2-adrenoceptor agonist salbutamol has been proposed to be stereoselective, presumably due to presystemic sulphate conjugation. In the present study we examined the stereochemistry of the sulphation reaction in vitro using human tissue preparations. 2. Sulphation of salbutamol was studied with partially purified hepatic M and P form phenol sulphotransferases (PSTs), 100,000 g cytosol of jejunal mucosa and platelet homogenate. The cosubstrate PAP35S was used as the sulphate donor. The acceptor substrate was either (+)-, (-)-or (+/)-salbutamol. 3. Sulphation was catalyzed by the M form PST of the liver but not the P form. The sulphation efficiency (Vmax/Km) was 11.9-fold greater for the (-)- than for the (+)- enantiomer, due entirely to a lower apparent Km for (-)-salbutamol, 103 microM, than for (+) salbutamol, 1394 microM. 4. Sulphation by the jejunal mucosa (n = 3) was very similar to that of the M form PST with the efficiency being 9.8-fold greater for the (-)-enantiomer and apparent Km values 95 microM and 889 microM for (-)- and (+)-salbutamol, respectively. 5. Sulphation by the platelet (n = 3) was also very similar to that of the M form PST with the efficiency being 9.9-fold greater for the (-)-enantiomer and apparent Km values 141 microM and 1190 microM for (-)- and (+)-salbutamol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485022 TI - The pharmacokinetics, tolerability and pharmacodynamics of tucaresol (589C80; 4[2 formyl-3-hydroxyphenoxymethyl] benzoic acid), a potential anti-sickling agent, following oral administration to healthy subjects. AB - 1. Tucaresol (589C80; 4[2-formyl-3-hydroxyphenoxymethyl] benzoic acid) interacts stoichiometrically with haemoglobin to increase oxygen affinity. By decreasing the proportion of insoluble deoxy sickle haemoglobin at capillary oxygen concentrations, tucaresol may be of therapeutic benefit in sickle cell anaemia. 2. In this study, which involved the first administration to man, the pharmacokinetics and pharmacodynamics of tucaresol were studied in healthy male volunteers following oral doses of 200-3600 mg. 3. Peak drug concentrations in plasma and erythrocytes were linearly related to dose; mean (s.d.) values were 95.8 (26.1) and 1035 (67) micrograms ml-1, respectively, at the highest dose. Median tmax in plasma was 6.5 h and in erythrocytes 24.5 h, when approximately 60% of the administered dose was in the target tissue. Plasma drug concentrations fell biexponentially with commencement of the apparent terminal elimination phase at approximately 24 h. The terminal elimination half-life from plasma increased with dose (r = 0.77; P < 0.0001) from 133-190 h at 400 mg to a mean (s.d.) of 289 (30) h at 3600 mg. Erythrocyte drug concentrations declined mono-exponentially with a half-life that was always shorter than the apparent terminal half-life in plasma: overall mean (95% CI) of t1/2 erythrocyte/t1/2 plasma ratio was 0.57 (0.53, 0.61). The erythrocyte AUC/plasma AUC ratio increased with dose (r = 0.67; P < 0.001). 4. The proportion of haemoglobin modified to a form with high oxygen affinity (%MOD) increased in a dose-related manner above doses of 800 mg reaching 19-26% after the 3600 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485023 TI - The metabolism of aprindine in relation to the sparteine/debrisoquine polymorphism. AB - 1. Incubation of the class I antiarrhythmic drug aprindine (AP) with human liver microsomes resulted in the formation of two hydroxylated metabolites (HA1 and HA2) and desethylaprindine which were identified by GC-mass spectrometry. In liver microsomes isolated from a poor metaboliser (PM) of sparteine no hydroxylated metabolites of AP were detected whereas AP N-dealkylation was unimpaired. Thus hydroxylation of AP is mediated by cytochrome P450 2D6 (CYP2D6). 2. AP was found to be a competitive inhibitor of CYP2D6 as indicated by its ability to impair the formation of (2S)-hydroxysparteine, 5,6-didehydrosparteine and 5-hydroxypropafenone by human liver microsomes. 3. These in vitro findings are consistent with a major role of CYP2D6 in the clearance of AP in vivo, with its ability to impair the metabolism of other CYP2D6 substrates in vivo, and an ability to cause phenocopying (conversion of extensive metaboliser phenotypes for sparteine/debrisoquine to apparent 'poor metabolisers). PMID- 8485025 TI - The effect of tocainide on theophylline metabolism. AB - The effect of 5 days of oral tocainide (400 mg every 8 h) on the kinetics of theophylline given as a single 5 mg kg-1 i.v. infusion over 30 min was investigated in eight healthy male nonsmokers. Treatment with tocainide decreased the plasma clearance of theophylline from 37.5 +/- 6.9 (mean +/- s.d.) to 33.7 +/ 5.0 ml kg-1 h-1 (difference -3.8, 95% CI, -1.7 to -5.9; P = 0.004) and increased its terminal elimination half-life from 9.7 +/- 2.5 to 10.4 +/- 2.1 h (difference 0.7, 95% CI, 0.2 to 1.2; P = 0.011). Tocainide decreased the formation clearances of 3-methylxanthine and 1-methyluric acid, but the formation clearance of 1,3 dimethyluric acid was unaltered. These data indicate that tocainide exerts a modest inhibitory effect on theophylline metabolism. The magnitude of this change is substantially smaller than that reported to be produced by mexiletine. PMID- 8485024 TI - Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. AB - 1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3 demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2. PMID- 8485026 TI - The pharmacokinetics of intravenous ondansetron in patients with hepatic impairment. AB - The pharmacokinetics of the 5-HT3 receptor antagonist ondansetron were investigated following a single 8 mg intravenous dose given over 5 min in 19 patients with varying degrees of hepatic impairment and in six young healthy subjects. In comparison with the healthy controls, the patients with severe hepatic impairment had a lower mean plasma clearance (96 ml min-1 vs 478 ml min 1) and increased AUC (1383 ng ml-1 h vs 279 ng ml-1 h) and t1/2 (21 h vs 3.6 h). These differences were all statistically significant (P < 0.001). The corresponding values for patients with mild or moderate hepatic impairment fell between these extremes. Vss was greater in all patient groups than the control group, but the magnitude of the change was smaller than for the other parameters and did not reflect the increasing severity of hepatic impairment. There were no significant changes in Cmax. There were no drug-related adverse events in the patients studied. It is recommended that the dosing frequency of ondansetron be limited to once daily in patients with severe hepatic impairment. PMID- 8485027 TI - The pharmacokinetics of quinine in patients with hepatitis. AB - The pharmacokinetics of quinine were studied in six patients with hepatitis B infection (during acute and convalescent periods) and six healthy subjects. A single 10 mg kg-1 dose of quinine was given intravenously over 2 h. Pharmacokinetic parameters of quinine during the acute phase of the infection were not different from those during the recovery phase. However, when compared with those obtained from healthy subjects, significant changes were found. The terminal elimination half-life was prolonged (17 and 15 vs 10 h) and clearance was lower (2.9 and 2.3 vs 3.5 ml min-1 kg-1). Unbound quinine concentration in plasma at 2 h was approximately 10% of the total concentration in all subjects in the three study groups. A prolonged QTc interval (< 25%) was observed in all groups. The present data suggest that current dosage regimens of quinine used in the treatment of falciparum malaria may not be suitable for malaria patients with acute hepatitis or those who have had hepatitis within the past 3 months. PMID- 8485028 TI - In vitro interaction between cyclosporin A and macrolide antibiotics. PMID- 8485029 TI - Maternal mortality in the Americas. PMID- 8485031 TI - Central American subregional meeting on theory and practice of public health. PMID- 8485030 TI - HIV and AIDS research in Latin America and the Caribbean: 1983-1991. PMID- 8485033 TI - Edging up tobacco taxes--differences between the United States and Canada. PMID- 8485032 TI - Trends in prostate cancer: United States, 1980 to 1988. PMID- 8485034 TI - Causes and management of headaches in cancer patients. AB - Headache is a frequent accompaniment of brain tumors. Since management of patients with these tumors is often palliative, proper treatment of symptoms such as headache becomes a key issue in preserving the patient's quality of life. Successful management of brain tumor headache requires an understanding of the etiology and pathophysiology of the various types of brain tumor headaches, followed by appropriate application of the specific therapeutic modality. PMID- 8485035 TI - Invasion and metastasis: new approaches to an old problem. AB - The progressive process of tumor invasion and generation of metastases is the primary cause of death for most patients with cancer. Recent advances have led to identification of novel sites for investigation and intervention. These advances include the definition of regulatory components of the metastatic cascade and characterization of the processes of angiogenesis, adhesion, proteolysis, and migration. This further understanding of the complex process of cancer progression has allowed the development of new diagnostic tools and potential therapeutic approaches. PMID- 8485036 TI - Psychosocial impact of cancer screening. AB - Cancer screening programs, including tests for early detection and programs aimed at identifying people with carcinogenic occupational exposure, may have psychological and behavioral sequelae. An abnormal screening result can lead to distress and anxiety that may continue even after further workup rules out cancer. Such psychological distress can affect subsequent health behavior. When testing or counseling indicates risk factors for cancer, the individual generally tries to adhere to the recommended preventive guidelines. A moderate amount of anxiety about the results may even be a motivating factor in getting subsequent check-ups. However, in some cases such knowledge leads to extreme levels of distress that can actually interfere with adherence behavior. Intervention studies now suggest that simple strategies can successfully reduce screening related anxiety. Such interventions are particularly important to assure that people with positive tests do not drop out of the system for future screening. PMID- 8485037 TI - What's new in the management of infectious diseases. AB - The 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held late last year in Anaheim, California. Sponsored by the American Society for Microbiology, the conference is designed to encourage the exchange of new information among microbiologists, clinicians, pharmacologists, pathologists, and members of related disciplines. The following highlights include those that may be of particular clinical interest to physicians in the oncology specialties. PMID- 8485038 TI - Incidence of non-Hodgkin's lymphoma in AIDS patients: sixty times greater. PMID- 8485039 TI - Expanded programme on immunization. An estimate of measles vaccine efficacy in a Canberra primary school. PMID- 8485040 TI - Diarrhoeal disease control (CDD) and acute respiratory infections (ARI). Combined CDD/ARI/breast-feeding survey, 1992. PMID- 8485041 TI - Influenza. PMID- 8485042 TI - Role of granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 in the eosinophilia associated with T cell lymphoma. AB - We studied two patients with a leukaemic T cell lymphoma who presented with a marked increase in blood eosinophilia. To investigate the mechanism of the eosinophilia, supernatants of peripheral blood cells containing more than 80% lymphoma cells were tested by biological assays for the presence of colony stimulating factors (CSF). In one case supernatants stimulated the growth of granulocyte-macrophage (GM), erythroid and eosinophil colonies. These effects were neutralized by anti-GM-CSF antibodies; anti-IL5 antibodies slightly decreased eosinophil colony formation. Supernatants derived from the second patient cells stimulated the same lineages. Neutralizing experiments demonstrated that in addition to GM-CSF it contained interleukin 3 (IL-3) and interleukin 5 (IL-5). In agreement with the biological data, RNA studies using the polymerase chain reaction showed that cells from the first patient expressed GM-CSF transcripts; IL-5 transcripts were also detected in very low amounts. GM-CSF, IL 3 and IL-5 transcripts were detected in cells from the second patient. Thus eosinophilia associated with some T cell lymphoma is likely due to secretion of different combinations of cytokines by malignant cells. PMID- 8485043 TI - Serum erythropoietin in patients with myelofibrosis with myeloid metaplasia. AB - Serum erythropoietin levels (s-Epo) were measured by radioimmunoassay in 61 consecutive anaemic patients (Hb < 12 g/dl) with myelofibrosis with myeloid metaplasia (MMM). S-Epo was inversely correlated with Hb (r = -0.48, P < 0.0001). When observed s-Epo values were compared with predicted levels based on the relationship between s-Epo and Hb in control subjects, all but eight patients (87%) had s-Epo levels appropriate for the degree of anaemia. The observed/predicted (O/P) s-Epo ratio was significantly lower in patients with signs of active disease, and a significant inverse correlation was found between the O/P ratio and erythrokinetic measurement of the extent of erythropoiesis (r = 0.31; P = 0.02). Circulating Epo levels were appropriate for the variations in Hb during the postsplenectomy period in three patients. In conclusion, this study does not support the idea that therapy with erythropoietin should be extensively used in anaemic patients with MMM, but rather that it should be considered only in selected cases. PMID- 8485044 TI - MDS-macrophage derived inhibitory activity on myelopoiesis of MDS abnormal clones. AB - We studied the effect of myelodysplastic syndrome (MDS)-derived adherent cells on colony formation of granulocyte-macrophage progenitors (CFU-GM) in both normal and MDS bone marrow cells. MDS-adherent cells suppressed the growth of normal CFU GM colony formation. Antibodies against ferritin almost totally neutralized the haematopoietic inhibitory activity. Antibody against gamma-interferon (gamma-IFN) did not have such effect. By cytogenetic analysis using G-staining method, MDS derived CFU-GM colony showed abnormal clones. MDS have been recognized to be a mosaic of normal and abnormal clones. MDS-macrophages suppressed the growth of progenitor cells derived from normal clones by soluble factors, but did not suppress the growth of those from abnormal clones. It is suggested that progenitor cells derived from abnormal clones are freed from the negative myelopoietic regulator that may be related to the progress of leukaemia. PMID- 8485045 TI - Impact of interferon alpha-induced cytogenetic improvement on survival in chronic myelogenous leukaemia. AB - The objective of this study was to investigate the prognostic impact of the reduction of Philadelphia chromosome (Ph) positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha. Therefore, we evaluated the outcome of patients with previously untreated chronic phase Ph positive CML, enrolled from 1984 to 1990 into two consecutive IFN trials at our institution. Of a total of 71 patients, 62 (87%) were evaluable for cytogenetic response. No cytogenetic improvement was seen in 16 patients (23%), 28 patients (38%) had a decrease in Ph-positive bone marrow metaphases to levels ranging from 35% to 95%, and nine patients (13%) to levels between 5% and 34%. In nine patients (13%), Ph-positive metaphases were no longer detectable. After a median follow-up period of 33 months, the projected 5-year survival is 55% for the 62 patients evaluable for cytogenetic response. In this patient population there was no significant difference in the survival probability according to patients' risk status as defined by the Sokal score. Categorization according to the extent of Ph reduction, however, allowed three groups with significantly different prognoses to be identified. Patients achieving a Ph reduction to less than 35% were found to constitute a low risk group with a median survival not yet known and a projected 5-year survival of 90%. The 5-year survival rate was 55% for patients with a Ph reduction to levels between 35% and 95%, and less than 10% for those without any cytogenetic improvement. Thus, this study demonstrates that cytogenetic improvement on IFN treatment is an important prognostic factor for survival. PMID- 8485046 TI - The significance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia. AB - In acute lymphoblastic leukaemia (ALL), minimal residual disease (MRD) can be defined as disease occurring at a subclinical level and beyond detection by conventional methods of assessment. Application of the polymerase chain reaction (PCR) to the hypervariable segment of the immunoglobulin heavy chain (IgH) gene, allows detection of MRD at a level of one leukaemic cell in 10(4)-10(5) normal marrow cells. We have performed a retrospective study using this technique in the assessment of children with precursor B-cell ALL in whom the clinical outcome is known. In the early treatment period MRD is commonly detected in children who remain in complete remission on subsequent follow up. Thus, the detection of MRD at this time may have little value in the prediction of future relapse. However, at the end of treatment, children who remain in complete remission have no evidence of MRD. Conversely, detectable MRD at this time would seem to predict for future relapse, though this can be a delayed event. Remarkably, in two children who suffered a bone marrow relapse 8.5 and 9 years after completing therapy for their initial disease, MRD was detected, in their end of initial treatment marrow samples. Clearly PCR technology is changing the definition of the remission state in childhood ALL, and may have predictive value in the assessment of children who are at a high risk of future relapse. Large prospective studies of molecular monitoring are now required to confirm these preliminary results. PMID- 8485047 TI - T cell function in children with acute lymphoblastic leukaemia. AB - Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukaemia (ALL) in children. However, once remission has been established, quality of life and even survival may be threatened by exacerbation of viral infections in the prolonged period of continuation therapy necessary to prevent relapse. Often the viruses involved in the most severe infections are from the herpesvirus and paramyxovirus groups, suggesting that patients suffer from a defect in the cellular immunity thought essential to control such cell associated infections. This may result from a T cell defect and, in this study, T cell responsiveness of patients under therapy for leukaemia has been investigated. In vitro proliferative responses of peripheral blood leucocytes (PBL) to the T cell mitogen phytohaemagglutinin (PHA) were impaired in children with ALL before treatment and in the induction of remission. Impairment was attributable to reduced T cell numbers, the presence of inhibitors in the patient's serum and direct damage to lymphocytes. On achieving remission, proliferative responses to PHA of both CD4+ and CD8+ T cell subsets quickly returned to normal levels with the switch to continuation chemotherapy. Proliferative responses to Herpes simplex virus antigens were also apparently normal in the majority of patients tested in remission. Further investigations, however, have suggested a persisting defect in CD8+ lymphocyte function. Gamma interferon secretion by PHA-stimulated PBLs was severely reduced for children with ALL in remission when compared with control children of similar age. Further, cytotoxic T lymphocyte responses to allogeneic cells could only be induced in PBL isolated from two of 13 children in remission from ALL whilst all control children of similar age and adults produced anti-allogeneic responses. PMID- 8485048 TI - Altered expression of the human retinoblastoma gene in monocytic leukaemias. AB - Inactivation of the retinoblastoma growth suppressor gene (RB) is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung carcinoma. Knowledge about the involvement of RB in the pathogenesis of myeloid leukaemias is still scarce. In this study we looked at the expression of the retinoblastoma gene product (p105) in 20 primary myelomonocytic and monoblastic leukaemias by Western blotting and immunocytochemistry using the anti-p105-monoclonal antibody PMG3-245. We found absence of or barely detectable levels of p105 in 11 patients (55%). Absence of or low levels of p105 were correlated with a higher leucocyte count at presentation (133 x 10(9)/l v 83 x 10(9)/l) and with the occurrence of extramedullary leukaemia (8/10 v 2/10). We conclude that abnormal expression of RB with absence of p105 or strongly reduced p105 levels occurs frequently in myelomonocytic and monoblastic leukaemias and that this may be correlated with a more malignant course of the disease. PMID- 8485049 TI - High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer. AB - Non-haematopoietic malignancies are commonly associated with thrombocytosis. The aetiology of tumour-associated thrombocytosis is still unclear but may be related to tumour-derived thrombopoietin-like factors. Epithelial ovarian tumour cells have been shown to release IL-6 in vitro and high IL-6 levels have been identified in ascites of patients with ovarian cancer. Since IL-6 is a potent stimulator of megakaryocytopoiesis we examined IL-6 production at the tumour site and its relationship to serum IL-6 levels and circulating platelet counts in patients with ovarian cancer. Forty patients undergoing exploratory laparotomy for epithelial ovarian cancer [stage I+II: 6 (15%); stage III: 25 (62.5%); stage IV: 9 (22.5%)] and 24 women with benign ovarian conditions were evaluated. Sera were available from 39 cases with ovarian cancer and from 19 cases with benign ovarian tumours. Ascites was obtained from 35 patients with ovarian cancer. IL-6 activity in serum and ascitic fluid was determined by the standard B9 proliferation assay (detection level: 1 pg/ml). IL-6 bioactivity was detectable in 22 (56%) sera from patients with ovarian cancer, but in only five (26%) of the serum samples obtained from benign cases (P < 0.001). Serum IL-6 levels in patients with ovarian cancer were significantly higher (median 3 pg/ml; range < 1 to 1221 pg/ml) than in patients with benign ovarian conditions (median 0 pg/ml; range < 1 to 4 pg/ml) (P < 0.001). However, much higher concentrations of IL-6 were measured in malignant ascites specimens (median 22,100 pg/ml; range < 1 to 182,600 pg/ml). IL-6 bioactivity in serum and ascites samples was completely inhibited by a neutralizing goat anti-human IL-6 antiserum. Thrombocytosis (platelet counts > 400 x 10(9)/l) occurred in 25 (62.5%) of the 40 patients with ovarian cancer, but in only two (8%) of the 24 cases with benign ovarian tumours. In eight (20%) cases with malignant disease platelet counts ranged between 600 x 10(9)/l and 1060 x 10(9)/l. IL-6 bioactivity in ascitic fluid correlated significantly with circulating platelet counts (r = 0.5916; P < 0.001). Maximum IL-6 bioactivity in ascites and highest platelet counts occurred in patients with undifferentiated ovarian adenocarcinoma or advanced disease. In conclusion, these observations strongly suggest a role for IL-6 in the development of tumour associated thrombocytosis. PMID- 8485050 TI - Identification of a nonsense mutation at amino acid 584-arginine of platelet glycoprotein IIb in patients with type I Glanzmann thrombasthenia. AB - Using Southern blot, the restriction digests of genomic DNAs in 11 patients with Glanzmann thrombasthenia from 10 unrelated kindreds were probed with a full length GPIIb cDNA. An additional 2.3 kb Taq I fragment and two 1.65 kb and 0.65 kb fragments with reduced band intensity were found in the genes of two affected siblings from a family originating from the city of Huang Yan in the Zhejiang province. The Taq I digest of the abnormal gene was further probed with three portions of GPIIb cDNA, revealing that the heterozygous mutation was present in the region around exons 15-17 of the GPIIb gene. Two primers for polymerase chain reaction (PCR) were then designed, and a 394 bp PCR product was generated and sequenced, indicating that a stop codon (TGA) was substituted for an Arg codon (CGA) at amino acid position 584 of GPIIb, and resulted in a premature termination of translation and production of a shortened protein. The Western blot analysis showed that GPIIIa at the platelet surface was apparently deficient, it may be ascribed to the rapid turn-over of GPIIIa uncomplexed with the truncated GPIIb. The abnormal 2.3 kb Taq I fragment was used as a specific genetic marker to detect the carrier status of the patient family. The abnormal allele was proved to be derived from the mother, the two affected siblings are double heterozygotes, and one clinically unaffected daughter has also inherited this defective allele, while the father carries another recessive abnormal allele unidentified. PMID- 8485051 TI - Mutations in haemophilia A. AB - In the present study DNA from 281 unrelated haemophilia A patients including 15 inhibitor patients has been analysed by Southern blotting technique. Using various restriction enzymes, cloned factor VIII cDNA probes and genomic fragments we have identified 14 mutations. Six of the mutations are novel partial factor VIII gene deletions. One deletion affects exon 1, two deletions concern exon 6, another deletion, of which breakpoints are sequenced, takes part of exon 16 and two deletions affect exon 26. Besides the deletions, eight point mutations have been found at the TaqI restriction sites of exons 18, 24 and 26. Five C-->T mutations resulted in nonsense mutations, one in exon 18, one in exon 26 and three in exon 24. Two G-->A mutations caused a missense mutation in exon 24 leading to an arginine/glutamine exchange. Although two patients showed this mutation, their clinical phenotypes were different, possibly due to an additional unidentified sequence polymorphism. A G-->T mutation in exon 26 substituted the arginine with leucine. All deletions and seven of the point mutations are associated with severe disease with a detectable inhibitor in the patient with the TaqI-point mutation in exon 18. One of the G-->A mutations is associated with mild haemophilia but the patient also has developed an inhibitor. Amongst these mutations the origin of the mutation could be determined in four kindred, one of which showed maternal mosaicism. PMID- 8485052 TI - Sickle cell disorders and chronic intravascular haemolysis are associated with low plasma heparin cofactor II. AB - Thrombotic events are known to be increased in patients with sickle cell syndromes and a variety of abnormalities of coagulation or endothelial function have been described, although the relevance of these findings either to the pathogenesis of vaso-occlusive phenomena or the risk of thrombosis are unclear. Heparin cofactor II (HCII) and antithrombin III are circulating inhibitors of thrombin and low plasma levels have been associated with an increased risk of thrombosis in otherwise healthy individuals. We describe for the first time abnormally low plasma levels of HCII in patients with sickle cell syndromes. 45 adult patients with sickle cell syndromes (31 SS, 10 SC, 4 S beta Thal) were compared with 61 age matched control patients for HCII in plasma. There was a highly significant reduction in HCII in SS patients irrespective of crisis or transfusion state 0.68 +/- 0.15 U/ml (mean +/- SD) compared with controls 1.00 +/ 0.19 U/ml (P < 0.001). HCII antigen was also significantly reduced (0.53 +/- 0.19 U/ml) compared with controls (1.02 +/- 0.23 U/ml, P < 0.0001). By contrast there was no reduction in antithrombin III in this group. HCII (0.63 +/- 0.13 U/ml, P < 0.001) and HCII antigen (0.54 +/- 0.08 U/ml, P < 0.001) are also significantly reduced in SC patients HCII levels increased towards control values during sickle cell crises, in patients taking the contraceptive pill, or with regular blood transfusion; however, plasma HCII concentrations were not increased acutely by exchange transfusion. HCII was also decreased in thalassaemia intermedia and pyruvate kinase deficiency, suggesting that intravascular haemolysis may be the cause of reduced HCII levels. PMID- 8485053 TI - Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet-derived microvesicles. AB - We have recently described the in vitro mechanism of action of anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies in patients with the antiphospholipid syndrome. LA antibodies inhibit coagulation reactions in plasma because they appear to recognize the complex of lipid-bound (human) prothrombin, whereas aCL antibodies require beta 2-glycoprotein I (beta 2-GPI) for binding to anionic phospholipids. aCL antibodies can be divided into two subgroups, according to their behaviour in lipid-dependent coagulation reactions: aCL-type A enhances the anti-coagulant effect of beta 2-GPI, whereas aCL-type B does not. In the present study we investigated the effect of purified aCL-type A and B and of LA antibodies on the procoagulant activity of both Ca-ionophore activated platelets and platelet-derived microvesicles, using an assay system with highly purified bovine coagulation factors Xa, Va, and prothrombin from human and bovine origin. In the absence of beta 2-GPI neither type of aCL was able to inhibit the prothrombinase activity of platelets or microvesicles. However, a strong and dose dependent inhibition of the prothrombinase activity of both platelets and platelet-derived microvesicles was observed within a few minutes, when aCL-type A antibodies were added in combination with beta 2-GPI. This inhibitory effect was dependent also on the concentration of beta 2-GPI. Conversely, no inhibitory effect of aCL-type B antibodies on platelet- (or microvesicle) prothrombinase activity in the presence of beta 2-GPI could be observed. LA antibodies were able to inhibit in a dose-dependent way the procoagulant activity of activated platelets and platelet-derived microvesicles. With two LA preparations this inhibition was only apparent when human prothrombin was used as substrate, while a third preparation exhibited its inhibitory effect both in the presence of human and bovine prothrombin. The data indicate that, in the presence of their respective cofactors beta 2-GPI and prothrombin, aCL and LA antibodies interact with the membrane of activated platelets and platelet-derived microvesicles in a very similar way as previously observed for their interaction with anionic phospholipid surfaces. PMID- 8485054 TI - Assessment of graft status following allogeneic bone marrow transplantation for haematological disorders in children using locus-specific minisatellite probes. AB - We have examined peripheral blood or bone marrow DNA following allogeneic bone marrow transplantation (BMT) in children suffering from a variety of haematological disorders. Using either locus-specific minisatellite probes separately or in combination with a Y specific probe for sex-mismatched transplants, complete haematological chimaerism, autologous reconstitution, or mixed chimaeric states have been defined immediately post-BMT. We have also been able to identify emerging autologous cells or relapse prior to morphological diagnosis. Forty-two children, mean age 6.4 years (range 9 months to 15 years), received an allogeneic BMT for: acute lymphoblastic leukaemia (ALL), n = 17; acute myeloid leukaemia (AML), n = 5; biphenotypic leukaemia, n = 1; myelodysplastic syndrome (MDS), n = 5; chronic granulocytic leukaemia (CGL), n = 1; severe aplastic anaemia (SAA), n = 7; familial erythrophagocytic lymphohistiocytosis (FEL), n = 2; beta thalassaemia major (beta thal), n = 1; and juvenile chronic myeloid leukaemia (JCML), n = 3. Immediately post-transplant, 78% had achieved complete haematological chimaerism, 12% had failed to engraft (DNA analysis confirmed autologous reconstitution) and 10% had mixed chimaerism. SAA was the underlying disease in two of the chimaeric cases, the third case having had a matched unrelated donor (MUD) BMT for MDS. In 3/4 cases which subsequently relapsed, DNA analysis showed re-emergence of autologous cells (indicative of relapse), prior to their morphological identification. We conclude that DNA analysis using minisatellite probes to assess graft status provides a useful contribution to patient management following allogeneic BMT. PMID- 8485055 TI - Dimethyl sulphoxide and haemin induce ferrochelatase mRNA by different mechanisms in murine erythroleukaemia cells. AB - The level of mRNA encoding ferrochelatase (FeC), the terminal enzyme of the haem biosynthetic pathway, was examined in murine erythroleukaemia (MEL) cells when they were induced to undergo erythroid cell differentiation by treatment with dimethyl sulphoxide (DMSO), or haemin. FeC mRNA increased within 12 h after DMSO or haemin treatment of MEL cells, and its level continued to increase for 48 h. Treatment of cells with succinylacetone (SA), a potent inhibitor of haem synthesis, suppressed a DMSO-mediated increase in FeC mRNA, and haemin treatment reversed a SA-mediated decrease in FeC mRNA. Nuclear runoff analyses showed that, while DMSO increased the rate of transcription of FeC mRNA, haemin did not. These results indicate that the induction of FeC mRNA by DMSO is largely transcriptional, while that by haemin is post-transcriptional. PMID- 8485056 TI - Iron status in red cell pyruvate kinase deficiency: study of Italian cases. AB - We investigated the iron status of 33 pyruvate kinase (PK) deficient patients, most of the cases reported in Italy. Serum ferritin (SF) was higher than the upper limit of the range of matched controls in 15/25 (60%) non-transfused patients (median 228 micrograms/l, range 58-3160 v 43, 22-310). Liver siderosis and fibrosis were found in 8/9, and cirrhosis in two who died at age 39 and 42 of complications of iron overload. SF was independent of age, sex, or severity of haemolysis. The prevalence of HLA-A3 antigen in PK deficient patients was not significantly different from that of our healthy population (29.6% v 23%). The HLA-A3 positive, non-transfused patients had significantly higher SF values than the HLA-A3 negative ones (median 675 micrograms/l, range 340-3160 v 145, 58-400). A pedigree study of six high SF-probands indicated that iron overload has a multifactorial pathogenesis. In particular, the association of PK deficiency induced haemolysis, splenectomy and an additional factor (heterozygosity for idiopathic haemochromatosis, ineffective erythropoiesis) leads to severe iron accumulation. We suggest that monitoring iron status would be useful in PK deficient patients, particularly in splenectomized and HLA-A3 positive ones, to identify those at risk of iron overload and prevent the clinical consequences of iron accumulation. PMID- 8485057 TI - Transient and persistent expansions of large granular lymphocytes (LGL) and NK associated (NKa) cells: the Yorkshire Leukaemia Group Study. AB - A survey of 870 different adult blood samples (primarily from patients with non haematological disorders) found that 269 (31%) had increased proportions (> 25%) and/or absolute numbers (> 1.0 x 10(9)/l) of morphologically-defined large granular lymphocytes (LGL), and/or phenotypically-defined NK-associated (NKa) cells. Of these, 112 were re-analysed at least 6 months after initial presentation and were classified as 'persistent' (92/112) or 'transient' (20/112) according to whether or not the original abnormality was still present. Lymphocyte counts in most patients with persistent abnormalities were within normal limits (18/92) or slightly increased (68/92), with only six having a lymphocytosis exceeding 10.0 x 10(9)/l. With the exception of five persistent LGL expansions in which the granular lymphocytes did not express NKa determinants (designated LGL+NKa-), the remaining 87 cases could be phenotypically grouped according to their primary abnormality as CD8+NKa+ (n = 33), CD4+ NKa+ (n = 14), CD8dim+NKa+ (n = 7) or CD8-NKa+ (n = 33). TCR genotypic studies in 58 patients showed that the 16 patients with rearranged TCR components were restricted to the CD8+NKa+ group and that, in most of these, the CD8+ fraction showed abnormal relative CD16/CD56 expression. Persistent neutropenia (n = 15) also appeared to be associated with primary abnormalities of CD8+NKa+ cells (12/15), with 10 of these additionally showing rearranged TCR genes. In contrast, persistently increased CD8dim+NKa+ and CD8-NKa+ components did not appear to phenotypically differ from their corresponding 'counterparts' in normal bloods or in patients with transient LGL/NKa+ abnormalities. This survey has therefore established that persistent LGL/NKa+ abnormalities are considerably more common than suggested in published work, that a high proportion of patients with expanded CD8+NKa+ components, with quite diverse clinical histories, show evidence of clonal lymphoid populations, and that the clonal nature of such disorders appears to be associated with abnormal NKa phenotypic patterns. PMID- 8485058 TI - Blood film features of sickle cell-haemoglobin C disease. AB - The blood films of patients with sickle cell-haemoglobin C disease (SC) were compared with those of patients with related haemoglobinopathies in order to establish the most characteristic features. The blood films from SC patients generally permitted the distinction from sickle cell anaemia (SS) but not necessarily from haemoglobin C disease (CC) or C/beta thalassaemia. About half of the SC films showed characteristic SC poikilocytes and a minority also had some cells containing haemoglobin C crystals. In addition, SC differed from SS in having fewer classical sickle cells and nucleated red cells, more irregularly contracted cells and less polychromasia and evidence of hyposplenism. PMID- 8485059 TI - Acute myeloid leukaemia following interferon-alfa treatment of hairy cell leukaemia. PMID- 8485060 TI - Omitting the antiglobulin crossmatch. PMID- 8485061 TI - Omitting the antiglobulin crossmatch. PMID- 8485062 TI - A new beta zero-thalassaemia nonsense mutation (codon 112, T-->A) not associated with a dominant type of thalassaemia in the heterozygote. PMID- 8485063 TI - Human mast cells in cases of cutaneous, systemic and malignant mastocytosis do not show immunohistochemically detectable overexpression of p53 protein. PMID- 8485064 TI - Platelet quality and reduction of HLA expression in acid-treated platelet concentrates. PMID- 8485066 TI - Nifedipine does not improve survival in AMI patients without heart failure. The SPRINT Study Group. PMID- 8485065 TI - Renal effects of xamoterol in patients with moderate heart failure. AB - The acute renal effects of xamoterol, a partial beta 1-agonist, were studied in 12 patients with congestive heart failure (NYHA II-III) in stable condition on diuretic therapy for at least 6 weeks. Each patient was given a single intravenous infusion of xamoterol (0.2 mg/kg) or placebo in random order 2 weeks apart. Using constant infusion and lithium clearance techniques, clearance and excretion measurements were made in the supine position at 30- to 60-min intervals before, during, and up to 6 hours after infusion. Blood pressure, heart rate, renal plasma flow, glomerular filtration rate, and urinary flow rate remained unchanged, but xamoterol lowered sodium excretion by 30% (p < 0.05). The decrease started 120 minutes after infusion. Proximal reabsorption of sodium increased after xamoterol infusion, whereas plasma values of aldosterone and angiotensin II were unaffected. It is concluded that the acute renal effects of xamoterol imply an impaired sodium excretion determined by the tubular actions of the drug. The present results suggest that xamoterol may aggravate one of the important abnormalities intrinsic to the pathology of congestive heart failure. These findings are in contrast to the beneficial effects of xamoterol demonstrated in many clinical trials where xamoterol was given orally for a longer period. PMID- 8485067 TI - A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris. AB - The antianginal activities of nicorandil, 10 and 20 mg bid, and metoprolol, 100 mg bid, were compared in patients with stable effort angina pectoris in a randomized, double-blind parallel group study lasting 7 weeks. Twenty patients were enrolled into the trial and 16 patients completed the study. To evaluate the anti-ischemic effects of the two drugs, a treadmill exercise test was performed after a 1-week placebo run-in period and 6 weeks of treatment. On the same occasions, weekly sublingual nitroglycerin consumption and the number of anginal attacks were also recorded in the patient's diary. The total duration of exercise increased significantly with both nicorandil, 10 and 20 mg, and metoprolol (p < 0.01). Similar improvements were observed in the time to onset of ischemia with both treatments (p < 0.01). The double product at maximal comparable workload (MAX 1) was reduced with the two drugs (p < 0.05 for nicorandil and p < 0.01 for metoprolol), while at the maximal exercise time (MAX 2) it was reduced with metoprolol (p < 0.01) and slightly but not significantly increased with both doses of nicorandil. Weekly sublingual nitroglycerin consumption and anginal attacks were also significantly reduced a similar manner by both treatments (p < 0.01). In conclusion, nicorandil, 10 and 20 mg bid, exerted an anti-ischemic effect comparable with that of metoprolol in patients with stable effort angina pectoris. PMID- 8485068 TI - Dose titration study of isradipine in Chinese patients with mild to moderate essential hypertension. AB - In order to assess the effective dose, tolerability, and safety of isradipine as a monotherapeutic antihypertensive agent for Chinese patients in Taiwan, an open trial was carried out. This study consisted of a 2-week, placebo, run-in period and an 8-week active treatment period, starting with isradipine 1.25 mg twice daily (bid) for the first 4 weeks, followed by 2.5 mg bid if the blood pressure was not normalized (diastole < 90 mmHg). One hundred and one patients (M/F = 48:53) were valid for efficacy analysis. Their age ranged from 30 to 64 years (mean +/- SD, 52 +/- 8). The blood pressure before active treatment was 160 +/- 2/104 +/- 1 mmHg. At the end of treatment period I (week 4), 12-14 hours after the last dose, 38 (37.6%) patients were normalized and 47 (46.5%) subjects responded (diastolic blood pressure reduction > or = 10 mmHg). At week 8, 68 (67.3%) patients were normalized and 79 (78.2%) subjects responded. Isradipine reduced both systolic and diastolic blood pressures within 2 weeks of treatment. There were no significant differences in blood pressure reduction between both genders and among age groups. Safety analysis showed two subjects with severe flushing, dizziness, and palpitation who used the dose of 1.25 mg bid. They withdrew from the study. The adverse reactions of other patients were transient, mild, and tolerable. Most of the side effects were related to vasodilatation, but edema was not found. There was no change in body weight or heart rate, nor any atrioventricular conduction disturbances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485069 TI - The therapeutic and diagnostic cardiac electrophysiological uses of adenosine. AB - Adenosine is a purine nucleoside with a rapid onset and brief duration of action after intravenous bolus administration. Its most prominent cardiac effect is impairment or blockade of atrioventricular nodal conduction, but other effects are depression of automaticity of the sinus node and attenuation of catecholamine related ventricular after-depolarizations. The cardiac cell surface receptor is the A1 purinoceptor. The therapeutic value of adenosine is predominantly in those arrhythmias in which the atrioventricular node forms part of a reentry circuit, as clearly demonstrated by the high success rate for termination of atrioventricular nodal reentry tachycardia and of atrioventricular reentry tachycardia involving an accessory pathway in the Wolff-Parkinson-White syndrome. Ventricular tachycardias are generally unresponsive, with the exception of right ventricular outflow tract tachycardia. A diagnostic role has emerged for adenosine. The transient blockade of the atrioventricular node that it causes can reveal important electrocardiographic features in arrhythmias, such as atrial flutter, or can unmask latent preexcitation. In wide-QRS tachycardias, adenosine can help to distinguish ventricular tachycardia from supraventricular tachycardia with QRS aberration. Unlike verapamil, adenosine is safe in ventricular tachycardia. A suggested dosing scheme is to give incremental doses at 1-minute intervals, starting at 0.05 mg/kg and continuing until complete atrioventricular block is induced or a maximum of 0.25 mg/kg is reached. Side effects are transient, sometimes uncomfortable, and not hazardous; dyspnea and chest discomfort are most frequent. A history of asthma is a relative contraindication. Aminophylline antagonizes and dipyridamole potentiates the effects of adenosine. PMID- 8485070 TI - Effects of trimetazidine on in vivo coronary arterial platelet thrombosis. AB - We used Folts' model of critical coronary artery stenosis with endothelial damage, which measures platelet-rich thrombus accumulation from cyclic flow reductions (CFRs). This paper reports results applied to trimetazidine, a member of the piperazine group. Trimetazidine at a dose of 1 mg/kg completely abolished CFRs caused by accumulating thrombus in the circumflex coronary artery in 4 of 8 open-chest anesthetized beagles. More trimetazidine (up to 5 mg/kg) abolished CFRs in two more and attenuated them in the remaining two dogs. There were no systemic hemodynamic effects observed. Adrenaline was then infused to stimulate platelet activation. At a rate of 0.4 microgram/kg/min, CFRs were restored in one dog only. Adrenaline given at 1.6 micrograms/kg/min resulted in restoration or increase in the slope of CFRs in all animals. A further six nonoperated dogs were anesthetized and given trimetazidine 3 mg/kg. Routine coagulation studies were not altered. However, aspirin 5 mg/kg significantly increased bleeding time, whereas trimetazidine alone did not. These findings suggest that trimetazidine is effective in preventing intracoronary platelet aggregation in this model. Because of its demonstrated sparing of coagulation factors and its lack of effect on bleeding time, the cause is unlikely to be inhibition of the fibrinogen or thrombin receptors, or interference with arachidonic acid metabolism. PMID- 8485071 TI - Influence of isosorbide dinitrate on superior mesenteric artery impedance in humans. AB - In a randomized, double-blind, placebo-controlled crossover study the acute effect of isosorbide dinitrate (ISDN) on the superior mesenteric artery velocity waveform was studied in 10 healthy subjects (mean age 48.2 years) over a 10 minute period. The superior mesenteric artery pulsatility index (PI), which quantifies the blood velocity waveform, increased from the second minute following sublingual administration of 5 mg ISDN (basal PI 4.88 +/- 0.32) and reached its upper level (8.22 +/- 1.38) from the fourth minute on. In comparison with placebo, the significant rise of PI (second minute) occurred before the significant decrease of systolic blood pressure (ninth minute) and before the significant increase in the heart rate (fourth minute). Diastolic and mean arterial blood pressures remained unchanged. These observations suggest an immediate vasoconstrictive effect of ISDN on the resistance vessels of the vascular bed of the superior mesenteric artery. PMID- 8485072 TI - Calcium antagonists for congestive heart failure: is it really one bridge too far to cross? PMID- 8485073 TI - Calcium antagonists for congestive heart failure: evolving concepts in bridge building. PMID- 8485074 TI - Transactional escalation in rigidity and intensity of interpersonal behaviour under stress. AB - The present study provides empirical support for a new interpersonal concept of transactional escalation. This proposition hypothesizes that an individual's typical pattern of interpersonal behaviour will become more extreme and rigid under stressful interpersonal conditions. Thirty Caucasian females participated in brief interviews that had two stages: low-stress and high-stress conditions. The half of the subjects who were assigned to a high-stress interview condition were predicted to show an escalation of their typical friendly-submissive patterns during the second half of the interview. Findings revealed that escalation was evidenced by an increase in the extremeness and rigidity of their interpersonal behaviour. Implications for interpersonal theory, and for diagnostic and psychotherapy endeavours are discussed and directions for future research are provided. PMID- 8485075 TI - The phases and focus of empathy. AB - Interpersonal empathy is a subtle and multisided phenomenon which can, nevertheless, lend itself to systematic portrayal and investigation. This paper further refines the author's account of empathy as involving a sequence of distinct steps or phases. Freshly introduced here is the idea of empathic response not only to self-experience but also towards relationships conceived as emergent living wholes with their own felt presence and individuality. Given described preconditions for empathy, three main phases in a complete empathic process are distinguished: reception and resonation by the listener; expressive communication of this responsive awareness by the empathizing person; and the phase of received empathy, or awareness of being understood. The phases are not a single closed system, thus do not occur in lock step and are semi-autonomous in practice. Responding empathically to relationship systems (existing as 'we' or 'us' to the participants and as a joint 'you' to others) may be interwoven with empathic response to individual 'I' experience. Although differing in focus, the empathic process follows the same phasic course in both cases. An underlying view is that individual selves are only one of the forms human life takes; other forms include relationships, families and living communities. PMID- 8485076 TI - The music therapy of an anorectic mentally handicapped adult. AB - Where words fail, music may be a medium through which to explore one's inner world and experiences. Psychodynamic approaches have helped us to understand what it means to be handicapped (e.g. Sinason, 1992). The subtleties of diagnosing anorexia nervosa have recently been recognized in this group (e.g. Cottrell & Crisp, 1984). Music therapy has been used with clients of normal intelligence who have eating disorders (Nolan, 1989; Sloboda, 1993; Smeijsters & van den Hurk 1993). This article illustrates the music therapy of a woman with Down's syndrome (IQ = 50) and anorexia nervosa. It describes her management and progress in music therapy in relation to her external world and anorectic behaviours. PMID- 8485077 TI - The role of psychological processes in the aetiology and treatment of cervical cancer: a biopsychological perspective. AB - Cervical cancer is one of the most serious illnesses affecting women today, particularly in developing societies. Despite medical advances in treatment and the success of cervical screening programmes in detection, the incidence of the disease is increasing. In this paper it is argued that one of the reasons for this is that the aetiological model employed for cervical cancer takes little account of psychological and psychophysiological factors. Both of these factors are now thought to play important roles in disease processes. Research in these areas is reviewed and a new aetiological model for cervical cancer described. This model incorporates existing epidemiological and medical formulations into a new multifactor framework. The implications of this model for treatment are explored and it is suggested that psychological interventions could play a much greater role than they have in the past. PMID- 8485078 TI - Crazy talk: thought disorder or psychiatric arrogance? AB - The crazy talk exhibited by some mental patients is re-examined. Our inability to understand the other is not a valid reason for concluding that he is insane, much less than he has a brain disease. The seemingly senseless speech of persons called 'psychotic' resembles glossolalia or the religious phenomenon of 'gift of tongues' rather than a speech disturbance, such as aphasia, indicative of brain disease. PMID- 8485079 TI - Thomas Szasz, crazy talk and the myth of mental illness. AB - In this article, Szasz's analysis of 'crazy talk' is considered in the context of his wider critique of psychiatric theory. We argue that Szasz has performed an important service by drawing attention to psychiatric prejudice regarding the causes of abnormal behaviour, and by pointing to the role of values in psychiatric decision making. However, Szasz may be criticized for his oversimple analysis of the concept of 'illness' and for his failure to recognize that values are central to all clinical decision making, including the diagnosis of physical illness. In the light of these criticisms we identify important weaknesses in his arguments about the incoherent speech of psychiatric patients. PMID- 8485080 TI - Comment on crazy talk: Thought disorder or psychiatric arrogance by Thomas Szasz. PMID- 8485081 TI - Post-traumatic anorexia nervosa--a case study. AB - The nature of the relationship between accidental trauma and psychopathology may not always be clear. Cases of post-traumatic anorexia nervosa have been described but without detailed attention to pre-existing psychopathological processes. This may give rise to spurious conclusions about direction of casualty. We describe a male patient who developed anorexia nervosa on two occasions, both episodes occurring during the convalescent period following traumatic accidents several years apart. The intervening period was characterized by strict self-regulation and conflict avoidance, typical of anorexia nervosa but with the body maintained at only a moderately low weight. We suggest that accidents can arise at times of crisis in such ongoing attempts at intense self-regulation. They may then reflect the escape from control of impulsivity and also provide an ultimate means of avoidance of further guilt-laden behaviour. They can be understood in the light of pre-existing psychopathology. The difficulties in early recognition and diagnosis of anorexia nervosa, especially in the male and in the absence of extreme weight loss are also discussed. PMID- 8485082 TI - Abnormal grief and eating disorders within a mother-son dyad. AB - A 50-year-old married woman with a history of recurrent depression developed a severe abnormal grief reaction following the death of her son (who had recovered from an eating disorder) in a car crash. The patient reported a number of bizarre rituals involving her son's ashes and personal effects obtained post mortem. She developed anorexia nervosa four months after his death. PMID- 8485083 TI - Perceived and desired facilitativeness of one's closest friend, need for approval and self-esteem. AB - The hypothesis that the positive association between self-esteem and the perceived facilitativeness of one's closest friend can be explained by the presumed greater desire of low self-esteem individuals for a facilitative relationship was not confirmed in 262 16-17-year-old females, who completed the Rosenberg (1965) Self-Esteem Scale and a shortened version of the Barrett-Lennard (1964) Relationship Inventory. Although desired facilitativeness correlated significantly positively with self-esteem, the correlation between perceived facilitativeness and self-esteem remained significantly positive when desired facilitativeness was partialled out. The further prediction that the correlation between perceived facilitativeness and self-esteem would be more positive for those scoring higher on the Jones' (1969) Need for Approval Scale was also not confirmed. The opposite result was obtained in that this correlation was significantly positive for those with low need for approval but not for those with a high need. PMID- 8485084 TI - Packaging of rhodopsin and porphyropsin in the compound eye of the crayfish. AB - The distribution of 3-dehydroretinal (Ral2) in dorsal, middle, and ventral slices of eyes of the crayfish Procambarus clarkii was examined by HPLC. No pronounced differences were found. Similar results were obtained when the eyes were cut into anterior, intermediate, and posterior portions. Dichroic difference spectra were measured in single halves of microvillar layers of isolated rhabdoms and the proportions of rhodopsin (P1) and porphyropsin (P2) estimated by comparison with computer-generated mixtures of these pigments, whose spectra are known from previous work. The fraction of visual pigment that is porphyropsin appears to be uniform throughout individual retinular cells and among the retinular cells of individual rhabdoms, but various substantially among different rhabdoms from the same eye. The interommatidial variation in the amount of P2 greatly exceeds the gross regional variation in Ral2. This means there is an intermingling of ommatidia with different levels of P2. The variability in P2 among ommatidia is not likely to have important implications for the vision of the crayfish but suggests that in the metabolism of retinoids, individual ommatidia are quasi independent metabolic units. The results are compatible with a single opsin for both crayfish rhodopsin and porphyropsin. PMID- 8485085 TI - Organotypic slice culture of the mammalian retina. AB - Vertical slices of 6-day postnatal (P6) rat retina were cut at a thickness of 100 microns and cultured using the roller-tube technique. After 14-21 days in vitro there was significant distortion of normal retinal architecture, but localized areas of the slices showed the typical pattern of layering of mature retina. The following immunocytochemical markers were used to characterize the different retinal cell types: antibodies against protein kinase C (PKC), calcium binding protein (CabP 28kD), neurofilaments (NF), glia-specific antibodies (GFAP, vimentin), and transmitter-specific antibodies (GABA, TH). The expression of these markers was compared in P6 retina, adult retina, and slice culture. To further characterize the cultured cells, patch-clamp recordings were performed in combination with intracellular injection of Lucifer Yellow (LY). Transmitter- and voltage-gated membrane currents were recorded from morphologically identified neurons. The experiments show that a mammalian slice culture can be used to study differentiation and function of retinal cell types. PMID- 8485086 TI - Mature, growing ganglion cells acquire new synapses in the retina of the goldfish. AB - The goldfish retina grows throughout the animal's life, primarily by a balloon like expansion. With this expansion, dendritic arbors of ganglion cells show scaled growth; arbors increase in size from small to large with no change in their architecture (Hitchcock & Easter, 1986; Bloomfield & Hitchcock, 1991). The study reported here showed that ganglion cell arbors acquire new synapses with this growth. Arbors from a single type of ganglion cell in retinas of small, young and large, old fish were intracellularly filled with horseradish peroxidase, examined electron microscopically, and the synapses contacting them counted and compared (small arbors vs. large arbors). The small and large arbors had similar numbers and orders of dendritic branches (i.e. similar architectures), but the large arbors were significantly larger than the small ones. The increase in arbor size was correlated with a 2.7x and 1.9x increase in the number of ribbon and conventional synaptic contacts, respectively. The addition of new synapses is proposed as a mechanism by which the signaling properties of the enlarging ganglion cells can remain constant. PMID- 8485087 TI - The histaminergic innervation of the lateral geniculate complex in the cat. AB - The histaminergic innervation of the thalamic dorsal and ventral lateral geniculate nuclei and the perigeniculate nucleus of the cat was examined immunohistochemically by means of an antibody to histamine. We find histamine immunoreactive neurons in the cat brain are concentrated in the ventrolateral portion of the posterior hypothalamus, confirming a previous report. However, this cell group also spreads into medial, dorsal, and extreme lateral regions of the posterior hypothalamus and extends as far rostral as the optic chiasm. Histamine-labeled fibers cover all regions of the lateral geniculate complex, but the density of labeling varies. The ventral lateral geniculate nucleus (vLGN) is most densely labeled, the A laminae of the dorsal lateral geniculate are sparsely labeled, and the geniculate C laminae and the perigeniculate nucleus show intermediate amounts of label. Thus, histaminergic fibers demonstrate a predilection for zones innervated by the W-cell system. Labeled fibers exhibit few branchings and numerous en passant swellings, lending a beaded appearance. The vLGN showed more instances of fibers with larger-sized swellings (up to 2 microns). Following injections of biotinylated tracers into the hypothalamus, we find labeled fibers throughout the lateral geniculate complex. The anterogradely labeled fibers resemble the histaminergic fibers in morphology, distribution, and relative bouton size. Thus, the hypothalamus appears to be the source of the histaminergic fibers in the lateral geniculate complex. Histamine-labeled fibers in the dorsal lateral geniculate nucleus (dLGN) exhibit uncommon ultrastructural morphology. Many extremely large, round, or elliptical vesicles fill the fiber swellings. Swellings are directly apposed to a variety of other dendritic and axonal profiles, but thus far no convincing synaptic contacts have been seen. The distribution and appearance of these histaminergic fibers resembles those reported for serotonergic fibers. Our results support the idea that histamine works nonsynaptically as a neuromodulator in the lateral geniculate complex, affecting the level of visual arousal. PMID- 8485088 TI - Selective depletion of beta cells affects the development of alpha cells in cat retina. AB - The results of previous studies suggest that class-specific interactions contribute to the development of the different classes of retinal ganglion cells. We tested this hypothesis by examining the morphologies and distributions of alpha (alpha) cells in regions of mature cat retina selectively depleted of beta (beta) cells as a result of visual cortex lesions at birth. We find that alpha cells in regions of central retina depleted of beta cells are abnormally large while alpha cells in regions of peripheral retina depleted of beta cells are abnormally small. The normal central-to-peripheral alpha cell soma-size gradient is absent in hemiretinae depleted of beta cells. The dendritic fields of alpha cells in the border of beta-cell-depleted hemiretina extend preferentially into the beta-cell-poor hemiretina. In spite of this, alpha cell bodies retain their normal retinal distribution and remain distributed in a nonrandom mosaic-like pattern. Thus, it appears that the development of alpha retinal ganglion cells is influenced by interactions both with other alpha cells (class-specific interactions) and with surrounding beta cells (nonclass-specific interactions). PMID- 8485089 TI - Brain stem and cortical contributions to the generation of horizontal optokinetic eye movements in humans. AB - We evaluated the subcortical pathways' contribution to human adults' horizontal OKN by using a method similar to that used previously with cats (Harris & Smith, 1990; Smith & Harris, 1991). Five normal adults viewed plaids composed of two drifting sinusoidal gratings arranged such that their individual directions of drift were 60 deg or more from the direction of coherent motion of the overall pattern. Physiological evidence indicates that under monocular viewing, nasalward coherent motion gives advantage to any crossed subcortical contribution while temporalward coherent motion minimizes it. We recorded horizontal eye movement by infrared reflection and asked subjects to report the perceived direction of motion. During both binocular and monocular viewing, the direction of the slow phase of OKN fell closer to the direction of coherent movement than to that of the oriented components. Monocular viewing produced no nasal-temporal asymmetries in the influence of coherent motion on the direction of OKN. This suggests that in humans the influence of coherent motion is mediated primarily by cortical mechanisms and, unlike in cats, with little or no involvement of subcortical mechanisms in the generation of horizontal OKN. PMID- 8485090 TI - Currents in the presynaptic terminal arbors of barnacle photoreceptors. AB - We have described the currents flowing across the presynaptic membranes of the four median photoreceptors of the giant barnacle, Balanus nubilus, using a quasi voltage clamp arrangement. Membrane potential, measured in the terminal region of one photoreceptor, was controlled in all four terminals by feedback current supplied through the nerve containing the photoreceptors' axons. The [Ca2+]o in the saline was reduced to decrease the Ca2+ current, enabling better voltage control, and tetraethylammonium ion (TEA, 20 mM) was added to block a fast voltage-dependent K+ conductance. Depolarizing voltage steps from the resting potential in the dark (-60 mV) evoked slow, inward Ca(2+)-dependent currents which could be blocked by Co2+, Mg2+, or Cd2+. The Ca2+ currents were followed by large outward currents that persisted for many seconds after the offset of moderate or large pulses. These tail currents increased in magnitude and duration with pulse duration and reversed at about -80 mV, consistent with previous evidence for a Ca(2+)-activated K+ conductance in this membrane. When the Ca(2+) activated outward current was reduced to zero by increasing the [K+]o so as to set EK at -20 mV, and then stepping the voltage to this value, the step evoked a steady inward Ca2+ current. Thus, the Ca2+ current did not show voltage- or Ca(2+)-dependent inactivation. When Ba2+ was substituted for Ca2+, 500-ms depolarizing steps evoked steady inward currents but no outward currents. In any given experiment, the activation voltage of the Ca2+ or Ba2+ current did not depend on holding potential. At the barnacle photoreceptor's synapse, the postsynaptic cell adapts to maintained presynaptic voltage by a mechanism that is not understood. We conclude that neither Ca2+ current inactivation nor a shift in activation voltage with holding potential can account for this adaptation. PMID- 8485091 TI - Gap-junctional properties of electrically coupled skate horizontal cells in culture. AB - Whole-cell voltage-clamp recordings were used to examine the unusual pharmacological properties of the electrical coupling between rod-driven horizontal cells in skate retina as revealed previously by receptive-field measurements (Qian & Ripps, 1992). The junctional resistance was measured in electrically coupled cell pairs that had been enzymatically isolated and maintained in culture; the typical value was about 19.92 M omega (n = 45), more than an order of magnitude lower than the nonjunctional membrane resistance. These data and the intercellular spread of the fluorescent dye Lucifer Yellow provide a good indication that skate horizontal cells are well coupled. The junctional conductance between cells was not modulated by the neurotransmitters dopamine (200 microM) or GABA (1 mM), nor was it affected by the membrane permeable analogues of cAMP or cGMP, or the adenylate cyclase activator, forskolin. Although resistant to agents that have been reported to alter horizontal-cell coupling in cone-driven horizontal cells, the junctional conductance between paired horizontal cells of skate was greatly reduced by the application of 20 mM acetate, which is known to effectively reduce intracellular pH. Together with the results obtained in situ on the receptive-field properties of skate horizontal cells, these findings indicate that the gap-junctional properties of rod-driven horizontal cells of the skate are fundamentally different from those of cone-driven horizontal cells in other species. This raises the possibility that there is more than one class of electrical synapse on vertebrate horizontal cells. PMID- 8485092 TI - A second episode of ganglion cell death takes place when an optic nerve regenerates for a second time in the frog. AB - We have previously reported that during optic nerve regeneration in the frog, 30 40% of retinal ganglion cells die, the loss being complete within 10 weeks. In the present study, we crushed the optic nerve, waited 10 weeks, and then recrushed the nerve at the same site. Retinae were examined 10 weeks later. We estimated ganglion cell numbers from cresyl-violet-stained wholemounts and found a fall of 53% compared to normals. The loss was significantly greater than the losses of 36% and 35%, respectively, in frogs which received a single optic nerve crush and were examined 10 or 20-24 weeks later. The results indicate that a second episode of ganglion cell death took place when the optic nerve regenerated a second time. We conclude that ganglion cells in the frog are not comprised of two subpopulations, only one of which intrinsically possesses the ability to regenerate. PMID- 8485093 TI - The segregation of ON- and OFF-center responses in the lateral geniculate nucleus of normal and monocularly enucleated ferrets. AB - We have investigated the distribution of ON- and OFF-center responses in the lateral geniculate nucleus of ferrets with normal and abnormal retinal projections. Electrophysiological recordings in normal pigmented animals confirm previous studies on mustelids showing that ON-center responses are found in the anterior, inner parts of laminae A and A1 and OFF-center responses in posterior, outer leaflets. In albino animals, lamina A displays normal patterns of ON/OFF segregation but in lamina A1', which receives an abnormal crossed retinal projection, no consistent patterns of segregation are found. Following monocular enucleation on the day of birth, the uncrossed projection in pigmented ferrets remains expanded across the LGN. Anatomically and physiologically, this projection is segregated into two leaflets: an anterior, inner ON-center leaflet and a posterior outer OFF-center leaflet. We conclude that the persistence of ON/OFF segregation, independent of geniculate location, suggests that self sorting of retinal input is an important factor in generating the segregation. PMID- 8485094 TI - Dendritic competition in the developing retina: ganglion cell density gradients and laterally displaced dendrites. AB - Dendrites of retinal ganglion cells (RGCs) tend to be distributed preferentially toward areas of reduced RGC density. This, however, does not occur in the retina of normal pigmented rats, in which it has been suggested that the centro peripheral gradient of RGC density is too shallow to provide directional guidance to growing dendrites. In this study, laterally displaced dendrites of RGCs retrogradely labeled with horseradish peroxidase were related to cell density gradients induced experimentally in the rat retina. Neonatal unilateral lesions of the optic tract produced retrograde degeneration of contralaterally projecting RGCs, but spared ipsilaterally projecting neurons in the same retina. These lesions created an anomalous temporal to nasal gradient of cell density across the decussation line, opposite to the nasal to temporal gradient found along the same axis in either normal rats or rats that had the contralateral eye removed at birth. RGCs in rats that received optic tract lesions had their dendrites displaced laterally toward the depleted nasal retina, while in either normal or enucleated rats there was no naso-temporal asymmetry. The lateral displacement affected both primary dendrites and higher-order branches. However, the gradient of cell density after optic tract lesions was less steep than the gradient in either normal or enucleated rats. To test for the presence of steeper gradients at early stages of development, RGC density gradients were also examined at postnatal day 5 (P5). In normal rats, the RGCs were homogeneously distributed throughout the retina, while rats given optic tract lesions at birth already showed a temporo-nasal density gradient at P5. Still, this anomalous gradient was less steep than that found in normal adults. It is concluded that the time course, rather than the steepness of the RGC density gradient, is the major determinant of the lateral displacement of dendritic arbors with respect to the soma in developing RGCs. The data are consistent with the idea that the overall shape of dendritic arbors depends in part on dendritic competition during retinal development. PMID- 8485095 TI - Brain-stem influence on visual response of lagged and nonlagged cells in the cat lateral geniculate nucleus. AB - This study examined the influence of the pontomesencephalic peribrachial region (PBR) on the visual response properties of cells in the dorsal lateral geniculate nucleus (LGN). The response of single cells to a stationary flashing light spot was recorded with accompanying electrical stimulation of the PBR. The major objectives were to compare the effects of PBR stimulation on lagged and nonlagged cells, to examine how the visual response pattern of lagged cells could be modified by PBR stimulation and to examine whether the physiological criteria used to classify lagged and nonlagged cells are applicable during increased PBR input to the LGN. During PBR stimulation, the visual response was enhanced to a similar degree for lagged and nonlagged cells and the latency to half-rise of the visual response was reduced, particularly for the lagged X cells. The latency to half-fall of the visual response of lagged cells was not changed by PBR stimulation. Accordingly, the division of LGN cells into lagged and nonlagged cells based on visual response latencies was maintained during PBR stimulation. The initial suppression that a visual stimulus evokes in lagged cells was resistant to the effects of PBR stimulation. For the lagged cells, the largest response increase occurred for the initial part of the visual response. For the nonlagged cells, the largest increase occurred for the tonic part of the response. The results support the hypothesis that the differences in temporal response properties between lagged and nonlagged cells belong to the basic distinctions between these cell classes. PMID- 8485096 TI - Differential staining of neurons in the human retina with antibodies to protein kinase C isozymes. AB - Monoclonal antibodies to the three isozymes of protein kinase C (PKC) (alpha, beta, and gamma) were applied to postmortem human retina. Immunostaining was done on wholemount, or cryostat-sectioned retina, and visualized after ABC/DAB procedures by light (LM) and electron (EM) microscopy. The PCK-alpha antibody stained rod bipolar cells throughout the retina. EM analysis confirmed they were PKC-alpha-immunoreactive (IR) on their characteristic dendritic and axonal synaptology. Putative blue cone bipolar cells with wide-field axon terminals, stratifying in s5 of the inner plexiform layer (IPL), were also PKC-alpha-IR, and EM showed them to engage in narrow-cleft ribbon junctions in blue cone pedicles. The PKC-beta antibody stained cone bipolar cells, many amacrine cells, and most ganglion cells. Cone bipolar cells were stained all the way into the foveal center: both midget and diffuse varieties were included. The IPL was densely PKC IR and individual neurons could not be identified on stratification patterns. EM of the outer plexiform layer (OPL) revealed that both flat and invaginating cone bipolar types were IR and that IR axon terminals were presynaptic in all strata of the IPL. The occurrence of PKC-beta-IR bipolar axons in stratum 2 of the IPL suggests that OFF-center as well as ON-center types were included. The PKC-gamma antibody gave inferior staining compared with results from the other two antibodies; however, two varieties of wide-field monostratified amacrine cell and a large-bodied ganglion cell type were discernible. PKC in one form or another appears to be a second messenger used in neurotransmission by both rod and cone systems and ON- and OFF-center systems in the human retina. PMID- 8485097 TI - Whole-cell currents activated at nicotinic acetylcholine receptors on ganglion cells isolated from goldfish retina. AB - We have recorded whole-cell membrane currents in response to exogenously applied acetylcholine (ACh), nicotine, and 1,1 dimethyl-4-phenyl piperazinium iodide on retinal ganglion cells enzymatically dissociated from goldfish retina. Agonist applications induced nicotinic-type responses in a majority of cells when cells were isolated under optimal conditions. Currents were reminiscent of nicotinic type ganglionic responses. Dose-response measurements of ACh-induced currents indicated an EC50 of 52 microM and a Hill coefficient of 0.6. Currents were selective for Na+ over Cl- and were highly inwardly rectifying. Responses were blocked reversibly by d-tubocurarine, hexamethonium chloride, and N-methyl-D glucamine. In 50% of the cases, alpha-bungarotoxin reversibly blocked the current induced by ACh application. The blocking action of mecamylamine was irreversible and independent of the presence of agonist but was more effective in the presence of ACh. We conclude that functional nicotinic ACh receptors exist on most goldfish retinal ganglion cells. PMID- 8485098 TI - Center/surround relationships of magnocellular, parvocellular, and koniocellular relay cells in primate lateral geniculate nucleus. AB - As in other primates, the lateral geniculate nucleus (LGN) of the prosimian primate, bush baby (Galago crassicaudatus), contains three morphologically and physiologically distinct cell classes [magnocellular (M), parvocellular (P), and koniocellular (K)] (Norton & Casagrande, 1982; Casagrande & Norton, 1991). The present study examined quantitatively the center/surround relationships of cells in all three classes. Estimates of receptive-field center size (Rc) and sensitivity (Kc) and of surround size (Rs) and sensitivity (Ks) were obtained from 47 LGN relay cells by fitting a difference of Gaussians function to contrast sensitivity data. For M and P cells, center size (Rc) increases with eccentricity but is about two times larger for M than for P cells at a given eccentricity. Surround size (Rs) increases with eccentricity for P but not for M or K cells. The center sensitivity (Kc) is inversely related to center size (Rc) and surround sensitivity (Ks) is inversely related to surround size (Rs) for cells in all classes, a result consistent with the sensitivity regulation that is produced by light adaptation. High spatial-frequency cutoff (acuity) is inversely related to center size (Rc). However, the peak contrast sensitivity is relatively independent of Rc. The ratio of the integrated strength (volume) of the surround to the volume of the center remains relatively constant (median, 0.87) across all three cell classes. This ratio is an excellent predictor of a cell's rolloff in contrast sensitivity at low spatial frequencies: cells with a low surround/center ratio have less low-frequency rolloff. Although M, P, and K cells generally display similar center/surround relationships, differences in center size and the other parameters between the classes distinguish most M, P, and K cells. These findings demonstrate that both similarities and differences in the visual response properties of primate LGN cells in these three parallel afferent pathways can be explained by basic center/surround relationships. PMID- 8485099 TI - The cone photoreceptor mosaic of the green sunfish, Lepomis cyanellus. AB - Recent empirical and theoretical evidence has implicated the geometrical birefringence of the double cones of the green sunfish (Lepomis cyanellus) as the biophysical basis of this vertebrate's sensitivity to polarized light. Because of the intimate link between the organization of the cone-photoreceptor mosaic and the psychophysical details of polarization sensitivity, we have examined the structural features of the green sunfish cone-photoreceptor mosaic, in particular the orientation of the elliptical cross sections of the double cones. Our primary observations are that (1) the arrangement of the cone-photoreceptor mosaic is constant across the retina (with two regional exceptions), with double cones arranged in a rhombic mosaic and aligned roughly +/- 45 deg to the nearest retinal margin; (2) the double-cone/single-cone ratio is everywhere the same; (3) cone density is inhomogeneous across the retina, with the highest densities in the temporal hemiretina. These results are discussed as they relate to the animal's retinal growth and visual mechanisms, particularly the sensitivity to polarized light. PMID- 8485100 TI - American Society of Regional Anesthesia, annual meeting. Seattle, Washington, May 13-16, 1993. Abstracts. PMID- 8485101 TI - Periodicity and sequence degeneration in eggcase precursors (vitelline proteins) from Fasciola hepatica. AB - Studies of two 3,4-dihydroxyphenylalanine (dopa) containing eggcase precursor proteins (vitelline proteins vpB1 and 2) from the trematode Fasciola hepatica recently concluded that although oligopeptide motifs occurred in the amino acid sequence, the overall structure (in contrast to dopa proteins from other phyla) was highly degenerate and irregular. An analysis of the distribution of individual amino acids and of oligopeptide motifs by two independent probabilistic pattern analysis methods, however, has now shown that despite superficial amino acid variability, an overall periodic structure exists. Moderately conserved hexadic domains account for almost 70% of the secreted protein, and characteristically contain glycine in position 5 of the hexad (76% of all glycine residues), and tyrosine, dopa or phenylalanine in positions 1 and 4 (88% of all aromatic residues). PMID- 8485102 TI - Hemicelluloses as structure regulators in the aggregation of native cellulose. AB - The influence of hemicelluloses on the aggregation of cellulose in higher plant cell walls was modelled by adding hemicelluloses to cultures of the cellulose producer Acetobacter xylinum. Characterization of the celluloses by X-ray diffractometry showed them to be more like those that occur in higher plants; the coaggregation of the hemicelluloses suggests their occlusion within and between the crystalline domains of the celluloses. The authors propose that hemicelluloses may be primary moderators of the tertiary structure of cell wall celluloses, allowing the development of a wide range of properties. PMID- 8485103 TI - Hydrodynamic characterization of chitosans varying in degree of acetylation. AB - The molecular weights and gross aqueous solution conformation of two chitosans of different degrees of acetylation, 'Sea Cure +210' (11% acetylated) and KN50 (58% acetylated) were characterized by viscometry, analytical ultracentrifugation and dynamic light scattering. The hydrodynamic parameters obtained were used to determine both the molecular weights and the gross solution conformation of the two chitosans. Using the Wales-Van Holde ratio of sedimentation coefficient concentration regression coefficient (ks) to intrinsic viscosity [eta], the Sea Cure +210 chitosan, which is much less acetylated than the KN50, is highly asymmetric in conformation. This, in conjunction with the charge on the molecule, would suggest a rod-like conformation in solution. The two largest KN50 chitosans have widely differing values for the Wales-Van Holde ratio, suggesting different solution conformation. However, when the series is examined as a whole using the Mark-Houwink-Kuhn-Sakurada relationships relating molecular weight to both intrinsic viscosity and translational diffusion coefficient, then a more spheroidal structure, approximating to a random coil, is predicted. PMID- 8485104 TI - Thermodynamic and kinetic studies of competitive inhibition of adenosine deaminase by ring opened analogues of adenine nucleoside. AB - Ring opened analogues of adenine nucleosides substituted at the ninth adenine positions, with and without esterification (compounds I and II), have been studied kinetically and thermodynamically at various temperatures in order to determine the sites of ring opened analogues. These are deemed to be important for binding to the adenosine deaminase. Adenosine deaminase is found to bind more strongly to compound I than to compound II, therefore compound I is a stronger inhibitor than II, because the position of (5') OH on the ribose moiety decreases the inhibitory strength on the ring opened analogue. PMID- 8485105 TI - Agarose chain conformation in the sol state by neutron scattering. AB - We report on small-angle neutron scattering investigations into the agarose conformation in water. We show that at 70 degrees C in the sol state agarose chains are fairly rigid with a lower limiting value for the persistence length of about 9 nm and a mass per unit length of muL = 360 +/- 36 g/mol x nm. The value of the latter parameter is consistent with single-stranded helices as those proposed recently by Foord and Atkins. Such a high rigidity together with such a low linear mass leads one to wonder how would the chains manage to intertwine should they form double helices in the gel state. PMID- 8485106 TI - Unfolding and refolding of the NAD(+)-dependent isocitrate dehydrogenase from yeast. AB - The unfolding of the NAD(+)-dependent isocitrate dehydrogenase from yeast in guanidinium chloride (GdnHCl) has been monitored by changes in c.d. and fluorescence. Major structural changes occur over the range of GdnHCl concentrations from 0.5 to 1.5 M, although loss of catalytic activity is complete at 0.3 M. After incubation in GdnHCl, activity can be regained on dilution; however, the extent of this regain is dependent on the initial concentration of GdnHCl and is very small at a concentration of 2 M or above. Under these conditions there is only limited regain of the secondary and tertiary structure of the enzyme. Considerably more structure and activity can be regained if the concentration of GdnHCl is lowered by dialysis. The implications of these results for the folding and assembly of the enzyme are discussed. PMID- 8485107 TI - Molecular bending and networks in a basement membrane-like collagen: packing in dogfish egg capsule collagen. AB - Low-angle X-ray diffraction data have been obtained from three mutually perpendicular axes through sheets of the collagenous egg capsule of the dogfish Scyliorhinus caniculus, a collagen that resembles type IV collagen. The data are interpreted in the light of the body of knowledge of the structure derived from transmission electron microscopy by Knight and Hunt. A model to account for the X ray data is proposed incorporating the main dimensions of the Knight and Hunt model which are confirmed by the diffraction data. Several features of the diffraction patterns are not explained by the existing model however, and a new model is proposed to account for these features. This consists of antiparallel packed pairs of two mutually parallel molecules, each kinked and rotated so as to produce a four-fold helix resembling a crankshaft. This has the advantage of conferring intermolecular linkage in three dimensions throughout the structure with tetragonal symmetry and unit dimensions a = b = 22.6 nm, c (fibre axis direction) = 39.3 nm. The result is a fairly rigid open polygonal network or sponge-like architecture that is capable of accommodating large quantities of water and other molecules. PMID- 8485108 TI - Refined structure of the aminobenzolamide complex of human carbonic anhydrase II at 1.9 A and sulphonamide modelling of bovine carbonic anhydrase III. AB - The binding of aminobenzolamide to human carbonic anhydrase (HCA II) has been investigated by X-ray crystallography. The three dimensional atomic structure of the enzyme inhibitor complex has been refined at 1.9 A resolution. The crystallographic R-factor is 17.8%. All inhibitor atoms are clearly possible to identify from the difference electron density map in the active site of the enzyme. The nitrogen of the sulphonamide group of the inhibitor is bound as a fourth ligand to the zinc ion, the other three are all histidyl residues. The binding conformation of the sulphonamide groups is similar to the previously described sulphonamide inhibitors. One of the oxygens of the outer sulphonamido group of the inhibitor forms a hydrogen bond to the amino group of Gln 92. The higher affinity of the benzolamide inhibitor compared with acetazolamide can be accounted for by the strong aromatic and hydrophobic interactions between the amino benzene ring of the inhibitor and the residues Phe 131 and Leu 198. In modelling studies of bovine carbonic anhydrase III (BCA III) it was evident that Phe 198 prevents an optimal interaction with sulphonamides. PMID- 8485109 TI - Skin concentration of 8-methoxypsoralen, 5-methoxypsoralen and 4,5,8 trimethylpsoralen in guinea pigs. AB - The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5,8-trimethylpsoralen (TMP) were studied in the albino guinea pig following oral administration and intraperitoneal injection. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 h, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5 ng/ml). The highest skin concentrations of 8-MOP and 5-MOP after intraperitoneal injection were achieved for both drugs at 0.5 h, with the level of 8-MOP approximately 1.3 times higher than that of 5-MOP. The level of TMP could not be measured even in the case of intraperitoneal injection. PMID- 8485110 TI - Simultaneous and separated culture of keratinocytes and fibroblasts on each side of a collagen membrane. AB - We have developed a new cell culture system which is of benefit for the research of dermal-epidermal interaction. In this system, normal human keratinocytes are cultured on the upper surface of a permeable collagen membrane, on the undersurface of which human fibroblasts are simultaneously and separately cultured in a lifted condition. Both the keratinocytes and fibroblasts showed good proliferation and differentiation which were revealed by phase contrast microscopy as well as light and electron microscopies. A permeability test of the collagen membrane used in the present study showed that peptides of less than 30 kDa are able to penetrate through the membrane. Using this system, we estimated the total protein content and cornified envelope formation in the keratinocytes cultured with or without fibroblasts. We found that the total protein and cornified envelope formation were significantly increased when keratinocytes were cultured together with fibroblasts. When keratinocytes were cultured with fibroblasts in the condition of air-liquid interface, synthesis of the cornified envelope was further enhanced. These results indicate that fibroblasts really effect not only the proliferation but also the differentiation of keratinocytes, and the air-liquid interface enhances their effect on differentiation. This bi phase separated cell culture system is a useful tool for the study of keratinocyte-fibroblast interaction. PMID- 8485111 TI - The location of Ted-R-1 antigen on the cell membrane of the stratum corneum: immunoelectron microscopic study. AB - As the Ted-R-1 monoclonal antibody yields fluorescence on the keratohyalin granules, in the cytoplasm of the lower stratum corneum cells and on the cell membrane region of the stratum corneum in indirect immunofluorescent examination, the location of the antigen of this Ted-R-1 monoclonal antibody was examined by the post-embedding, immunoelectron microscopic technique using gold labelled antibody. The number of gold particles located on the keratohyalin granules was 184.00 +/- 28.69 per micron2. In contrast, there were only a few gold particles in the nucleus and the cytoplasm of the stratum granulosum (3.85 +/- 1.34) and none were found in the intercellular spaces of these cells (< 1.00). On the other hand, they were diffusely located in the lower two to three cell layers of the stratum corneum (319.75 +/- 44.41) and on the inner surface of the marginal band of the upper cell layers of the stratum corneum, but only a few were located in the cytoplasm of the upper stratum corneum cells (12 +/- 7.00). These observations indicate that the Ted-R-1 antigen locates on both keratohyalin granules and the inner surface of the marginal band of the upper part of the stratum corneum cell layers. PMID- 8485112 TI - Proteoglycans in cultures of skin fibroblasts in recessive dystrophic epidermolysis bullosa. AB - The proteoglycans of cultured fibroblasts from the skin of three patients with recessive dystrophic epidermolysis bullosa and three normals were compared after labeling with [35S]sulfate and [3H]leucine. The behavior in gel chromatography of the intact proteoglycans and several properties of their component glycosaminoglycans (size, content of iduronic acid, and content of 4- and 6 sulfate) showed no statistical differences. In addition, the binding of intact proteoglycans and of their constituent proteins and glycosaminoglycans to type I collagen were measured by affinity chromatography. No differences were found that could account for the skin lesions in recessive dystrophic epidermolysis bullosa. PMID- 8485113 TI - A proposed guideline for psoralen photochemotherapy (PUVA) with atopic dermatitis: successful therapeutic effect on severe and intractable cases. AB - Psoralen photochemotherapy with UVA (PUVA) has been reported to be successfully substitutional for, or an adjunct to, conventional treatments in patients with atopic dermatitis (AD). Against the considerable advantages of utilizing PUVA for AD patients, however, it must also be balanced against the possible hazards for individual patients. We attempted herein to formulate a guideline for the selection of AD patients assigned to PUVA. According to this guideline, 114 patients were selected for PUVA treatment. Forty-five percent of the patients did not respond adequately to other conventional forms of treatment. Side effects from former treatments, particularly steroids, appeared in 39% of the patients. Subsequent to the treatments, the skin lesions significantly decreased in 81% of the inpatients and 67% of the outpatients, while some patient's lesions disappeared, despite that other forms of treatment had been unsuccessful in many cases. PMID- 8485114 TI - Substrate delivery as a determinant of hepatic apoB secretion. AB - The evidence that apoB particles secreted by the liver can differ in number and composition has been reviewed. No evidence has yet emerged that changes in apoB100 itself affect the rate of its secretion from the liver. The metabolic role of apoB appears to be the prevention of lipid accumulation within the liver cell: when delivery of lipid to the liver increases, apoB secretion will increase pari passu. This reality in no way detracts from the critical role played by the LDL receptor in determining the number of LDL particles in plasma, nor does it diminish the potential importance of intracellular processes such as 7 alpha hydroxylase activity to also mediate LDL receptor activity. However, it should be obvious that variation in catabolism by itself cannot explain all that has been observed in physiological and pathological studies. On the contrary, the whole process must be taken into account--the rate at which apoB particles are added to the circulation, the rate at which they are converted to LDL, and the rate at which they are irreversibly removed from plasma--if we are to understand and appreciate this most peculiar and most important of transport systems. PMID- 8485115 TI - Nifedipine inhibits accumulation of LDL and cholesterol in the aorta of the normocholesterolemic rabbit. AB - The effect of 5 days of oral nifedipine treatment (approximately 1 mg/kg per day in drinking water) on low density lipoprotein (LDL) and cholesterol accumulation in rabbit arteries was determined. Compared with control aortas, nifedipine treatment (n = 5) significantly reduced homologous 125I-tyramine cellobiose-LDL accumulation (control versus nifedipine: 45.93 +/- 4.3 versus 20.14 +/- 3.1 ng LDL per milligram dry weight x10(-3), p = 0.001) while the reduction of human LDL accumulation (n = 5) was not significant (49.1 +/- 6.1 versus 35.5 +/- 4.1 ng LDL per milligram dry weight x10(-3)). Aortic accumulation of orally administered [3H]cholesterol was also inhibited by nifedipine (352 +/- 34 versus 257 +/- 16 ng cholesterol per milligram dry weight x10(-3), n = 10, p = 0.022). These findings suggest a possible mechanism for the antiatherosclerotic effect of nifedipine. PMID- 8485116 TI - Prevalence and risk factors of asymptomatic extracranial carotid artery atherosclerosis. A population-based study. AB - To evaluate the prevalence and risk factors of asymptomatic carotid artery disease, we analyzed a sample of 909 men and women (aged 40-79 years) drawn from the community-based Bruneck Ischemic Heart Disease and Stroke Prevention Study. For the four decades of age (40-49, 50-59, 60-69, and 70-79 years), respective prevalence rates as assessed by duplex scanning were found to be 8.2%, 39.7%, 66.4%, and 82.5% in men and 3.3%, 22.3%, 48.7%, and 76.7% in women. High-grade stenosis (> 80%) classified by Doppler criteria was twice as frequent in men (2.4%) as in women (1.1%). Age and sex were found to be particularly strong and independent predictors of asymptomatic carotid artery disease. Accordingly, separate logistic regression models were developed for both men and women in the elderly (65-79 years) and middle-aged (50-64 years) groups. Systolic blood pressure turned out to be the only attribute with independent significance in all subgroups examined. Cigarette smoking, recorded as pack-years, emerged as the leading risk factor of carotid atherosclerosis in men. Serum fibrinogen levels were found to be highly indicative of carotid artery disease in elderly men and women. For apolipoprotein B predictive significance was observed in the middle aged populations, whereas apolipoprotein A-I had a protective effect in elderly women. Diabetes mellitus completed the risk factor profile for elderly men. In summary, the relation between cardiovascular risk factors and asymptomatic carotid artery disease showed a dynamic dependence on sex and age. These findings may help to improve the efficacy of risk prediction in the general population and facilitate well-directed preventive measures. PMID- 8485117 TI - Plasminogen activator inhibitor-1 mRNA is expressed in platelets and megakaryocytes and the megakaryoblastic cell line CHRF-288. AB - Plasminogen activator inhibitor-1 (PAI-1) is present in the platelet alpha granule and is released on platelet activation. Platelet PAI-1 could either be synthesized by the megakaryocyte or taken up from the plasma. In this report we confirm the presence of PAI-1 protein in human megakaryocytes by Western blot analysis and show its synthesis in guinea pig megakaryocytes by metabolic labeling. We document the presence of PAI-1 mRNA in human platelets and show a 3 kb mRNA species on Northern blot analysis of guinea pig megakaryocytes. Neither untreated CHRF-288 cells, a megakaryoblastic cell line, nor human erythroleukemia (HEL) cells expressed PAI-1 mRNA. Phorbol ester (phorbol 12-myristate 13-acetate, 160 nM) treatment of CHRF-288 and HEL cells for 4 days induced PAI-1 mRNA expression in CHRF-288 cells but not in HEL cells. These studies show that PAI-1 is synthesized by megakaryocytes. Megakaryocytes most likely determine the PAI-1 content of platelets and thereby establish the antifibrinolytic potential of the platelet. PMID- 8485118 TI - Relation between sex hormones and serum lipoprotein and lipoprotein(a) concentrations in premenopausal obese women. AB - Lipoprotein(a) (Lp[a]) is generally considered to be a risk factor for the development of cardiovascular disease, but little is known about the possible influence of obesity on the circulating levels of this lipoprotein. The present study was undertaken to examine this aspect in 136 menstrually active women by comparing the serum concentrations of Lp(a) between 72 obese and 64 age-matched nonobese women. Since an adverse effect of androgens and a protective effect of estrogens have been described for plasma lipoprotein profiles in obese women, the relation between the circulating levels of Lp(a) and those of these other hormones was also investigated in obese patients. In addition, other lipoproteins, anthropometric parameters (body mass index and waist-to-hip ratio), and insulin were evaluated. The levels of Lp(a) were not significantly different (Mann-Whitney U test chi 2, 3.59; p = 0.0582 [NS]) between obese (rank sum, 5,367) and control (rank sum, 3,949) women; in addition, the percentage of patients with high Lp(a) levels (cutoff defined at 30 mg/dL) did not differ between the two groups (obese women, 30%; control, 21.8%; chi 2, 0.90; two-sided p = 0.341 [NS]). Moreover, no correlation was found between Lp(a) and body mass index. Lastly, when the Lp(a) prevalence odds ratio for obesity was examined by adjusting the levels of this lipoprotein for age, triglycerides, total cholesterol, and high density lipoprotein cholesterol, the probability value (0.88) was far from significant. In obese women, no correlation was found between the logarithmically transformed Lp(a) concentrations and all the other variables evaluated in the study. In conclusion, the present study shows that the circulating levels of Lp(a) are not influenced by body weight and cardiovascular risk factors commonly associated with obesity, such as enhanced androgenic activity, hyperinsulinemia, adverse lipoprotein profile, and abdominal fat accumulation. PMID- 8485119 TI - Basic fibroblast growth factor in the extracellular matrix suppresses collagen synthesis and type III procollagen mRNA levels in arterial smooth muscle cell cultures. AB - To determine the effects of an intact extracellular matrix on collagen synthesis, arterial smooth muscle cells (SMCs) were plated sparsely on a cell-free, SMC derived matrix and examined the following day. Collagen synthesis during a 5-hour incubation by cells on the matrix was reduced to 67% of the control values obtained from cultures on plastic. Total protein synthesis was unaffected. Treatment of the matrix with heparitinase to remove basic fibroblast growth factor (bFGF) before seeding the SMCs abolished the inhibitory effect of the matrix on collagen synthesis. The inhibitory effect was also eliminated by treating the matrix with a neutralizing polyclonal antibody directed against bFGF. Collagen synthesis by SMC cultures grown in wells coated with purified bFGF was only 61% that of control cultures, whereas total protein synthesis remained unchanged. Slot-blot analysis revealed that the relative message level for alpha 1(III) procollagen was reduced in cultures grown on the preexisting matrix or on plastic precoated with bFGF, whereas the alpha 1(I) procollagen message was unaffected. These results demonstrate the ability of the extracellular matrix to modulate the synthesis of collagen by arterial SMCs and indicate that bFGF in the matrix is responsible for these effects. PMID- 8485120 TI - Genetics of LDL subclass phenotypes in women twins. Concordance, heritability, and commingling analysis. AB - Low density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small LDL as determined by gradient gel electrophoresis, has been associated with increased risk of coronary heart disease and an atherogenic lipoprotein profile. Previous studies employing complex segregation analysis have demonstrated a major, single gene effect on the inheritance of this phenotype in families. Recently, linkage between this phenotype and variation at the LDL receptor locus on chromosome 19 has been reported. However, variation in LDL subclass phenotypes has also been associated with age, gender, diabetes status, beta-blocker medication, and diet. The present study further evaluates the relative importance of genetic and nongenetic influences on LDL subclass phenotypes and on LDL peak particle diameter (as a reflection of the size of the major LDL subclass) in monozygotic and dizygotic women twin pairs. The analysis is based on 203 monozygotic and 145 dizygotic pairs of adult female twins who participated in the second examination of the Kaiser Permanente Women Twins Study. The average age was 51 years at this exam and 90% were white. Concordance analysis revealed that monozygotic cotwins shared LDL subclass phenotypes more frequently than dizygotic cotwins, and this was confirmed using logistic regression analysis after controlling for potential confounding factors. Heritability analyses suggested that approximately one third to one half of the variation in LDL peak particle diameter, a continuous variable reflecting LDL size, could be attributed to genetic influences. Commingling analysis of the frequency distribution of LDL peak particle diameter identified three distinct subgroups of subjects, one of which corresponded to those subjects with LDL subclass phenotype B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485121 TI - Platelet aggregation induced by the endoperoxide analogue U46619 is inhibited by polymorphonuclear leukocyte ADPase activity. AB - Platelet activation by the stable endoperoxide analogue U46619 is mediated largely by ADP released from platelet-dense granules. Polymorphonuclear leukocytes (PMNs) endowed with ecto-ADPase activity may operate as antiaggregatory cells in platelet aggregation induced by U46619. Unstimulated PMNs were effective in reducing aggregation when platelets were stimulated by threshold concentrations of U46619, whereas at higher concentrations of the stimulus, PMN activation is required. Evidence that the inhibition was mediated by PMN ecto-ADPase activity was obtained by high-performance liquid chromatography analysis, indicating that PMNs were able to efficiently metabolize platelet-active ADP into AMP. Moreover, PMN-derived supernatants were able to inhibit platelet aggregation, suggesting that under this circumstance the inhibition was exerted by an uncharacterized, releasable ADPase activity. This study supports the hypothesis that, besides nitric oxide and hydrogen peroxide, ADPase activity may represent another PMN-mediated pathway capable of regulating platelet activity in areas of reduced blood flow, such as those found in conditions of myocardial ischemia. PMID- 8485122 TI - Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia. AB - Metabolic heterogeneity in low density lipoprotein (LDL) may be detected by examination of the daily urinary excretion rate of radioactivity after injection of trace-labeled lipoprotein. Two distinct pools are observed within LDL. The first (pool A) is cleared rapidly from the plasma, whereas the second (pool B) is catabolized more slowly. In the present study we examined LDL metabolism in seven hypercholesterolemic subjects (six women and one man) before and during fenofibrate therapy. Comparison with normocholesterolemic individuals showed that the pretreatment high LDL levels in the hypercholesterolemic subjects resulted from an accumulation of apoprotein-LDL (apo-LDL) mass in pool B (2,077 +/- 174 mg versus 787 +/- 70 mg in normal subjects, p < 0.002). Pool A apo-LDL was present at normal levels (approximately 1,000 mg), although its fractional catabolic rate was reduced (0.39 +/- 0.06 versus 0.61 +/- 0.03 pool/day in normal subjects, p < 0.01). Fenofibrate therapy (100 mg t.i.d. for 8 weeks) produced substantial reductions in plasma cholesterol (29%; p < 0.001), triglycerides (36%; p < 0.001), and LDL cholesterol (30%; p < 0.001). The latter was associated with a 30% decrease in circulating apo-LDL mass (2,312 +/- 200 mg versus 3,279 +/- 264 mg before treatment, p < 0.005). This resulted from a combination of two effects. First, although overall LDL apoprotein B production did not change, there was a shift from pool B to pool A. Pool A input was 400 +/- 74 mg/day pretreatment versus 706 +/- 62 mg/day on fenofibrate; pool B input was 422 +/- 35 mg/day pretreatment versus 258 +/- 41 mg/day on the drug. At the same time, catabolism of pool A rose from 0.39 +/- 0.06 to 0.66 +/- 0.08 pool/day (p < 0.05). We hypothesize that the shift from pool B to pool A resulted from a drug-induced decrease in the particle size of very low density lipoprotein made by the liver, which in turn favored the formation of more rapidly catabolized LDL. Overall, the rate of apo-LDL degradation by the receptor route (as detected using a combination of native and 1,2-cyclohexanedione-modified LDL tracers) rose 43% on the drug, whereas the amount cleared by the receptor-independent pathway did not change. Fenofibrate, therefore, appears not only to promote LDL catabolism via the receptor-mediated pathway but also, by lowering plasma triglyceride levels, inhibits the formation of slowly metabolized, potentially atherogenic LDL particles. PMID- 8485123 TI - Identification of multiple dense LDL subfractions with enhanced susceptibility to in vitro oxidation among hypertriglyceridemic subjects. Normalization after clofibrate treatment. AB - The influence of different plasma triglyceride concentrations on the heterogeneity of low density lipoprotein (LDL) and on the susceptibility of LDL to copper oxidation was investigated. By density gradient ultracentrifugation, LDL subfractions were isolated from the plasma of 10 normolipidemic control subjects and 12 hypertriglyceridemic patients both before and after clofibrate treatment. In the plasma of control subjects three LDL subfractions were present: LDL1 (d = 1.030-1.033 g/mL), LDL2 (d = 1.033-1.040 g/mL), and LDL3 (d = 1.040 1.045 g/mL). In the plasma of nine moderately hypertriglyceridemic subjects up to five LDL subfractions could be detected: LDL1-LDL3, LDL4 (d = 1.045-1.049 g/mL), and LDL5 (d = 1.049-1.054 g/mL). This polydispersity of LDL was replaced by monodispersity with increasing plasma triglyceride concentrations in three subjects with chylomicronemia, in whom LDL was concentrated in the narrow LDL5 density range. Clofibrate treatment resulted in a lighter LDL subfraction pattern (LDL1-LDL4). In both the control and the moderately hypertriglyceridemic subjects, the small dense LDL subfractions appeared more prone to oxidative modification in vitro than the light LDL subfractions, as measured by the decreased lag time preceding the onset of lipid peroxidation. Furthermore, the dense LDL subfractions were more extensively modified over time, as shown by an increased oxidation rate and a greater number of dienes formed after 6 hours of oxidation. These results suggest an enhanced atherogenic potential of the small, dense LDL subfractions within each LDL subfraction profile. The hypertriglyceridemic LDL subfractions before therapy (LDL3-LDL5) were less resistant to in vitro oxidation than the light, control LDL subfractions (LDL1 LDL3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485124 TI - Hepatic lipase deficiency. Clinical, biochemical, and molecular genetic characteristics. AB - Hepatic lipase (HL) is an important enzyme in the metabolism of triglyceride-rich lipoproteins and high density lipoproteins. The clinical syndrome of HL deficiency is rare and difficult to identify. We studied carriers of mutant HL to ascertain whether there are distinctive clinical and/or biochemical characteristics of the heterozygous state. In an Ontario kindred, compound heterozygosity for two HL mutations, S267F and T383M, underlies the clinical syndrome of complete HL deficiency. We report that simple heterozygotes for either HL mutant do not have a discrete lipoprotein abnormality, except for relative triglyceride enrichment of lipoprotein fractions with d > 1.006 g/mL. Postheparin HL activity is depressed to a greater degree in carriers of S267F compared with carriers of T383M. Retinyl palmitate loading studies in a compound heterozygote revealed impaired clearance of chylomicron remnants. The dyslipoproteinemia in a compound heterozygote was ameliorated by lovastatin. There was no difference in the quantity and distribution of HL mRNA in the liver of a compound heterozygote when compared with that of a normal subject. Thus, HL deficiency associated with structural variation of the HL gene is characterized by premature atherosclerosis, triglyceride enrichment of lipoprotein fractions with d > 1.006 g/mL, the presence of circulating beta-very low density lipoproteins, and abnormal catabolism of postprandial triglyceride-rich lipoproteins. PMID- 8485125 TI - Intravenous and endobronchial administration of G4120, a cyclic Arg-Gly-Asp containing platelet GPIIb/IIIa receptor-blocking pentapeptide, enhances and sustains coronary arterial thrombolysis with rt-PA in a canine preparation. AB - G4120, L-cysteine, N-(mercaptoacetyl)-D-tyrosyl-L-arginylglycyl-L-alpha- aspartyl cyclic(1-->5)-sulfide, 5-oxide, a synthetic cyclic Arg-Gly-Asp-containing pentapeptide, has a high affinity (dissociation constant of 4 nM) for the platelet glycoprotein (GP) IIb/IIIa receptor. The effects of its intravenous or endobronchial administration on thrombolysis, reocclusion, and bleeding time prolongation induced with 0.45 mg/kg bolus injections of recombinant tissue-type plasminogen activator in combination with intravenous heparin (4,000-unit bolus and 1,000 units each hour) were studied in a canine model consisting of an erythrocyte-rich blood clot in the left anterior descending coronary artery. Coronary patency was monitored for 3 hours both by ultrasonic flow probe and by repeat coronary angiography. Four groups of six to 10 dogs were studied with intravenous infusions of 0, 0.1, 0.2, or 0.3 mg/kg G4120 over 60 minutes. G4120 at a dose of 0.3 mg/kg reduced the time to reflow from a mean control value of 45 to 8 minutes (p = 0.036) and delayed reocclusion (p = 0.001). Four groups of five or six dogs were studied with endobronchial instillation of G4120 in a randomized, blinded study design using 0, 0.13, 0.25, or 0.5 mg/kg G4120. Endobronchial G4120 at a dose of 0.5 mg/kg reduced the time to reflow from a mean control value of 52 to 7 minutes (p = 0.039) and abolished cyclic reocclusion and reflow (p = 0.008). G4120 induced a dose-related transient prolongation of the template bleeding time and inhibition of ADP-induced platelet aggregation. G4120, a synthetic low-molecular-weight GPIIb/IIIa inhibitor that may be produced by chemical synthesis, may be of clinical value as a conjunctive agent for thrombolysis in patients with ischemic coronary syndromes. PMID- 8485126 TI - Isolation of heparin-insensitive aortic smooth muscle cells. Growth and differentiation. AB - Previous work has shown heparin and heparan sulfates to be potent inhibitors of vascular smooth muscle cell (VSMC) growth. This laboratory has previously isolated a VSMC line insensitive to the antiproliferative action of heparin by subjecting VSMCs that grew out from rat aortic medial explants to continuous passage in media containing heparin at 200 micrograms/mL. In the present study, we have isolated two additional heparin-resistant (HR) cell lines and have used the HR cells to investigate cellular mechanisms responsible for the potent antiproliferative activity of heparin. In contrast to normal heparin-sensitive VSMCs, the HR cells were smaller, displayed elongated processes, and possessed altered growth characteristics; however, both HR and normal cells bound and internalized comparable amounts of heparin. Immunohistochemical detection of smooth muscle cell-specific actin in growth-arrested cells showed staining of nearly all normal VSMCs and of a much smaller percentage of HR cells; heparin treatment caused a marked increase in the percentage of HR cells expressing smooth muscle cell alpha-actin, indicating that the antiproliferative and differentiation-promoting actions of heparin are independent. Proteins from control VSMCs and HR cells were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and heparin affinity chromatography. Several proteins were expressed preferentially by either HR cells or normal VSMCs, with the most significant difference being the secretion of a high-affinity, heparin-binding protein (M(r), 38,000) by control VSMCs but not by HR cells. We conclude that the aortic VSMC population may give rise to HR cells under selective conditions and that their unique characteristics, such as alterations in their ability to produce heparin-binding proteins, will prove useful in deciphering the cellular mechanisms involved in heparin's regulation of VSMC growth and differentiation. PMID- 8485127 TI - Molecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family. AB - Alzheimer's disease is a degenerative neurological disorder characterized by neural loss and brain lesions associated with plaques containing large amounts of the beta/A4 amyloid peptide. Molecular cloning of the cDNA for this peptide from human brain has shown it to be derived by proteolysis from a much larger precursor called the amyloid precursor protein (APP). The biological role of the precursor is unknown, but it has been shown to be transcribed in many human tissues in addition to brain. In the present report, we describe the molecular cloning from a human placental library of a full-length cDNA for a molecule closely related to APP. This novel molecule, which we have called amyloid precursor protein homolog (APPH), shares overall domain organization with APP. It is 763 amino acids in length and appears to encode a signal peptide, a large apparent extracellular domain including a Kunitz inhibitor domain, a transmembrane region, and a short cytoplasmic domain. Northern analysis indicates that it occurs in at least two molecular forms and is transcribed in human brain, heart, lung, liver, and kidney, in addition to placenta. On the basis of its extensive sequence similarity and conservation of domain structure, APPH is the nearest relative of APP yet identified in an emerging multigene family. PMID- 8485128 TI - Kinetic and spectroscopic studies of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase II. AB - The functional importance and structural determinants of a conserved hydrophobic pocket in human carbonic anhydrase II (CA II) were probed by preparing and characterizing 13 amino acid substitutions at Leu-198, situated at the mouth of the pocket. The pH dependence of the esterase activity reveals that activity decreases (up to 120-fold) as the amino acid size and charge at position 198 are varied while the pKa of the zinc-bound water molecule increases (up to 1 pH unit). Intriguingly, the pH dependence of the Leu-198-->Glu substitution is parabolic (pKas approximately 6 and 9), consistent with introduction of a general base-catalyzed mechanism. Kinetic characterization of CO2/HCO3- interconversion catalyzed by four variants (Leu-198-->Ala, His, Arg, and Glu) reveals that increasing the size of the hydrophobic pocket (Ala) does not compromise catalysis (approximately 3-fold decrease); however, substitution of charged (Arg and Glu) and larger (His) amino acids decreases kcat/KM for CO2 hydration substantially (17-fold, 19-fold, and 10-fold, respectively) but not completely. log kcat/KM for CO2 hydration, HCO3- dehydration, and p-nitrophenyl acetate hydrolysis correlates with the hydrophobicity of the residue at 198, likely reflecting desolvation or electrostatic destabilization of the ground state. The X-ray crystal structures of the Leu-198-->His, Glu, and Arg variants (Nair & Christianson, 1993) indicate that the His and Glu side chains are accommodated by minor structural reorganization leading to a wider mouth for the hydrophobic pocket while the Arg side chain blocks the pocket. Infrared spectroscopy of CO2 bound to either wild type CA II or the Leu-198-->Arg variant indicates that the Arg substitution both decreases the affinity and alters the position of CO2 binding, suggesting that the hydrophobic pocket forms the CO2 binding site in CA II. Finally, a 1.5-fold increase (Leu-198-->Ala) and 12-fold decrease (Leu-198-->Arg) in kcat for CO2 hydration, indicative of the rate constant for intramolecular proton transfer from zinc-bound water to His-64, are likely mediated by changes in the active site solvent structure. PMID- 8485129 TI - Structural consequences of hydrophilic amino acid substitutions in the hydrophobic pocket of human carbonic anhydrase II. AB - The three-dimensional structures of Leu-198-->Glu, Leu-198-->His, Leu-198-->Arg, and Leu-198-->Ala variants of human carbonic anhydrase II (CAII) have each been determined by X-ray crystallographic methods to a resolution of 2.0 A. The side chain of Leu-198 is located at the mouth of the active site hydrophobic pocket, and this pocket is required for substrate association. Hydrophobic-->hydrophilic amino acid substitutions at the mouth of the pocket decrease kcat/KM for CO2 hydration: the CO2 hydrase activities of Leu-198-->Glu, Leu-198-->His, and Leu 198-->Arg CAIIs are diminished 19-fold, 10-fold, and 17-fold, respectively, relative to the wild-type enzyme; however, the substitution of a compact aliphatic side chain for Leu-198 has a smaller effect on catalysis, in that Leu 198-->Ala CAII exhibits only a 3-fold decrease in CO2 hydrase activity [Krebs, J. F., Rana, F., Dluhy, R. A., & Fierke, C. A. (1993) Biochemistry (preceding paper in this issue)]. It is intriguing that CO2 hydrase activity is not severely diminished in Leu-198-->Arg CAII, even though the side chain of Arg-198 blocks the hydrophobic pocket. Therefore, the bulky side chain of Arg-198 must be reasonably mobile in order to accommodate substrate association. Significantly, a residue larger than the wild-type Leu-198 side chain does not necessarily block the substrate association pocket; e.g., the side chain of Glu-198 packs against a hydrophobic patch, the net result of which is a wider mouth for the pocket.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485130 TI - Fourier transform infrared spectroscopy and electrochemistry of the primary electron donor in Rhodobacter sphaeroides and Rhodopseudomonas viridis reaction centers: vibrational modes of the pigments in situ and evidence for protein and water modes affected by P+ formation. AB - Protein electrochemistry in an ultra-thin-layer electrochemical cell suitable for UV/vis and IR spectroscopy has been used to characterize the vibrational modes of the primary electron donors of Rhodobacter sphaeroides and Rhodopseudomonas viridis reaction centers in their neutral and cation radical states (P and P+, respectively). The P-->P+ redox transitions could be well separated from redox reactions of other cofactors according to their redox midpoint potential. The IR difference bands of the primary electron donor bacteriochlorophylls all titrate in unison and exhibit the correct midpoint potential. Comparison of the difference spectra with those of isolated bacteriochlorophylls a and b in organic solvents of different polarity and proton activity [Mantele, W., Wollenweber, A. M., Nabedryk, E., & Breton, J. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8468 8472] leads to similar conclusions on the binding and interaction of the pigments within the protein matrix as previously obtained from light-induced P+Q-/PQ difference spectra. Equilibration of the reaction centers in D2O leads to few but distinct shifts of bands and changes of band intensities at 1662, 1634, and 1526 cm-1 (Rhodobacter sphaeroides) and 1694, 1664, 1648, 1630, and 1532 cm-1 (Rhodopseudomonas viridis) as well as to smaller deviations at other wavenumbers. The H-->D-sensitive band at 1662 cm-1 is interpreted in terms of a histidine NH2+ bending mode. A second H/D-sensitive difference band around 1648 cm-1 in the Rhodopseudomonas viridis reaction center may be associated with the peptide C = O of one of the amino acids surrounding P [eventually of the histidine(s) ligating the Mg] which is affected by P+ formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485131 TI - R and T states of fluoromethemoglobin probed by ultraviolet resonance Raman spectroscopy. AB - Ultraviolet resonance Raman spectra are reported for the fluoride complex of methemoglobin (metHbF), with and without added inositol hexaphosphate (IHP), an allosteric effector known to stabilize the T quaternary structure. Environmental changes in Trp and Tyr residues give rise to the difference features, which are similar to those observed in the difference spectrum between deoxyHb and the CO adduct, consistent with T-state formation in metHbF in the presence of IHP. There are, however, important differences. The intensities of the difference signals are attenuated by about one-third, indicating a lower T-state population in the IHP-bound metHbF than in native deoxyHb. And a new signal is seen which arises from the interior tryptophans, probably reflecting a change in their H-bond status associated with the presence of fluoride as the sixth heme ligand in the T state. Implications of these results for the nature of the molecular forces opposing ligation in the T state are discussed. PMID- 8485132 TI - Inter-tryptophan distances in rat cellular retinol binding protein II by solid state NMR. AB - Structural constraints for the tryptophans in rat cellular retinol binding protein II (CRBP II) have been obtained by rotational-echo double-resonance (REDOR) solid-state NMR. CRBP II was labeled with L-[6-19F]tryptophan and L-[2 13C]tryptophan. The 13C-19F dipolar coupling was determined for various possible tryptophan geometries. The allowed distance between the closest two of the four tryptophans in CRBP II was obtained for each geometry. The minimum possible distance between these two tryptophans in CRBP II is 7 A, and the maximum possible distance is 11 A. PMID- 8485133 TI - Inhibitor-induced conformational change in cytochrome P-450CAM. AB - The X-ray crystal structures of cytochrome P-450CAM complexed with both enantiomers of a chiral, multifunctional inhibitor have been refined to R-factors of 21.0% [(+)-enantiomer] and 19.6% [(-)-enantiomer] at approximately 2.1-A resolution. Binding of either enantiomer, both considerably larger than the natural substrate camphor, results in similar, dramatic structural changes in the enzyme. In contrast to all previous P-450CAM crystallographic structures, the Tyr96 side chain is not pointing "down" toward the heme but is rather directed "up" into the proposed substrate access channel. This conformational change is accompanied by the displacement of the Phe193 side chain out into the solvent at the enzyme surface. These changes are consistent with the assignment of this region of the enzyme as the access channel [Poulos et al. (1986) Biochemistry 25, 5314-5322] and suggest that several aromatic residues lining the channel may be involved in substrate recognition and channeling to the active site. The cation usually observed coordinated to the Tyr96 carbonyl oxygen is missing in the presence of the (+)-enantiomer but is present with the (-)-enantiomer. The Phe87 side chain, located near the inhibitor binding site, adopts different orientations depending upon which enantiomer is bound. Finally, electron density reveals that although the inhibitor enantiomers were dichlorinated as provided, when bound to P-450CAM the chlorine atoms are present at only 0-20% occupancy, probably reflecting selective binding of impurities in the samples. Coordinates of these inhibited P-450CAM complexes have been deposited in the Brookhaven Protein Data Bank [Bernstein et al. (1977) J. Mol. Biol. 112, 535-542]. PMID- 8485134 TI - Effect of pH on solubility and ionic state of lipopolysaccharide obtained from the deep rough mutant of Escherichia coli. AB - The dissociation of the highly aggregated form of lipopolysaccharide (LPS) from Gram-negative bacteria to the monomeric (or soluble) form is though to be the initial step in the activation of responding cells (macrophages, B-cells, neutrophils, monocytes, and endothelial cells) by LPS. This process is presently not adequately understood. Using the equilibrium dialysis apparatus and a highly purified and well-characterized radiolabeled deep rough chemotype LPS ([14C]ReLPS) from Escherichia coli D31m4, we have examined the effect of pH on its solubility (CT) and ionic states in aqueous media. The solubility range of [14C]ReLPS suspended in 50 mM Tris-HCl-100 mM KCl buffer (or 50 mM MES-100 mM KCl buffer at pH 6.5) was determined to be from (2.91 +/- 0.01) x 10(-8) to (4.55 +/- 0.07) x 10(-8) M over a pH range of 6.50-8.20, respectively. These experimental data satisfactorily fitted the curve generated by the solubility equation CT = S0(1 + K5/[H+])/([H+]/K4' + 1), where S0 is the concentration of the tetraanionic ReLPS, K5 is the dissociation constant of the tetraanionic ReLPS in solution, and K4' is the dissociation constant of the trianionic ReLPS at the surface of the solid particles in suspension. The increase in solubility of ReLPS with increase in pH from 7.00 to 8.20 is primarily caused by the formation of the pentaanionic form from the tetraanions. The pK5 (primarily the second dissociation of the 1 phosphate) of ReLPS was determined to be 8.58 from experimental data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485135 TI - Phosphorylation of human and bovine prothymosin alpha in vivo. AB - Prothymosin alpha is post-translationally modified. When human myeloma cells were metabolically labeled with [32P]orthophosphoric acid, they synthesized [32P]prothymosin alpha. The incorporated radioactivity was resistant to DNase and RNases A, T1, and T2, but could be completely removed by alkaline phosphatase. No evidence was found for an RNA adduct as postulated by Vartapetian et al. [Vartapetian, A., Makarova, T., Koonin, E. V., Agol, V. I., & Bogdanov, A. (1988) FEBS Lett. 232, 35-38]. Thin-layer electrophoresis of partially hydrolyzed [32P]prothymosin alpha indicated that serine residues were phosphorylated. Analysis of peptides derived from bovine prothymosin alpha and human [32P]prothymosin alpha by treatment with endoproteinase Lys-C revealed that the amino-terminal 14-mer, with serine residues at positions 1, 8, and 9, was phosphorylated at a single position. Approximately 2% of the peptide in each case contained phosphate. Further digestion of the phosphopeptide with Asp-N followed by C18 reversed-phase column chromatography produced two peptides: a phosphate free 9-mer containing amino acids 6-14 and a labeled peptide migrating slightly faster than the N-terminal 5-mer derived from the unmodified 14-mer. Positive identification of the phosphorylated amino acid was obtained by colliding the 14 residue phosphopeptide with helium in the mass spectrometer and finding phosphate only in a nested set of phosphorylated fragments composed of the first three, four, and five amino acids. The results prove that prothymosin alpha contains N terminal acetylserine phosphate. In a synchronized population of human myeloma cells, phosphorylation occurred throughout the cell cycle. Furthermore, prothymosin alpha appeared to be stable, with a half-life slightly shorter than the generation time. Although prothymosin alpha is known to be essential for cell division, the constancy of both the amount of the protein and the degree of its phosphorylation suggests that prothymosin alpha does not directly govern mitosis. PMID- 8485136 TI - Cholesterol is poorly available for free apolipoprotein-mediated cellular lipid efflux from smooth muscle cells. AB - To study the mechanism for resistance of smooth muscle cells (SMC) to cholesterol efflux caused by lipid-free apolipoproteins [Komaba, A., et al. (1992) J. Biol. Chem. 267, 17560-17566], the efflux of phospholipids and cholesterol was induced from mouse peritoneal macrophages (MP) and rat aortic SMC by phospholipid/triglyceride microemulsion, by human plasma high- and low-density lipoproteins (HDLs and LDLs), and by lipid-free human apolipoprotein (apo) A-I. The efflux of both lipids by the lipid microemulsion showed essentially the same kinetic profile for these two types of cells except that the rate of phospholipid efflux was 5-6 times slower by weight than cholesterol in both cases. The same ratio of cholesterol to phospholipid was also found in the efflux to LDLs. Lipid free apoA-I mediated cellular cholesterol efflux, but the rate was much slower from SMC than from MP. However, the rate of apoA-I-mediated phospholipid efflux was similar between these two cells generating HDL-like particles, resulting in a high phospholipid:cholesterol ratio, (4-5):1 by weight, in the lipid efflux from SMC, in contrast with (0.8-1):1 in the lipid efflux from MP. When standardized for the cellular free cholesterol, the Vmax of cholesterol efflux induced by lipid-free apoA-I was 10 times slower from SMC than from MP, but only by at most 2-fold slower when lipid microemulsion was the acceptor. Thus, free cholesterol of SMC is less available than that of MP for free apolipoprotein-mediated generation of HDLs with cellular lipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485137 TI - Unfolded structure and reactivity of nucleosome core DNA-histone H2A,H2B complexes in solution as studied by synchrotron radiation X-ray scattering. AB - It has been previously found using different physicochemical techniques [Aragay, A., Diaz, P., & Daban, J.-R. (1988) J. Mol. Biol. 204, 141-154] that histones H2A,H2B in the absence of H3,H4 can associate with nucleosome core DNA (146 base pairs). Here we describe a synchrotron X-ray scattering study of core DNA (H2A,H2B) complexes in solution. Our results obtained using different histone to DNA weight ratios and ionic conditions ranging from very low ionic strength to 0.2 M NaCl show that histones H2A,H2B are unable to fold core DNA. Model calculations indicate that histones H2A,H2B produce very elongated structures even when the reconstituted complexes are prepared at physiological ionic strength. In contrast, our scattering data indicate that the reconstituted complexes prepared at physiological salt concentration either with the four core histones or with histones H3,H4 without H2A,H2B are completely folded particles with a radius of gyration similar to that corresponding to the native nucleosome core (4.2 nm). Furthermore, our results show that the DNA of the extended complexes containing histones H2A,H2B becomes completely folded after the histone pair exchange reaction that occurs spontaneously between preformed DNA-(H2A,H2B) and DNA-(H3,H4) complexes. These observations, together with our previous studies, suggest that the open conformation of DNA-(H2A,H2B) complexes facilitates the involvement of this structure as a transient intermediate in the reaction of nucleosome formation at physiological ionic strength. PMID- 8485138 TI - Translesional synthesis on DNA templates containing 8-oxo-7,8 dihydrodeoxyadenosine. AB - This study was designed to establish the miscoding potential of 8-oxo-7,8 dihydrodeoxyadenosine (8-oxo-dA). Oligodeoxynucleotides modified site specifically with 8-oxo-dA were used as templates in primer extension reactions catalyzed by DNA polymerase I (Klenow fragment), DNA polymerase alpha (pol alpha), or DNA polymerase beta (pol beta). dTMP or dGMP is incorporated opposite 8-oxo-dA when either of these dNTPs is provided as substrate for DNA polymerase. dTMP is incorporated exclusively opposite 8-oxo-dA when all four dNTPs are present in the reaction mixture at equimolar concentrations. Chain extension is catalyzed efficiently by Klenow fragment and pol beta under conditions where 8 oxo-dA is paired with dT at the 3' terminus of the primed DNA template. Chain extension catalyzed by pol alpha proceeds more slowly. As shown by steady-state kinetic experiments, incorporation of dGMP is higher in reactions catalyzed by pol beta than by Klenow fragment or pol alpha. The dG-8-oxo-dA pair is extended efficiently from the 3' terminus in the absence of dTTP. We conclude that DNA containing 8-oxo-dA is capable of miscoding; however, unlike 8-oxo-dG, the mutagenic potential of this lesion is limited. PMID- 8485139 TI - New insights into sequence recognition process of esperamicin A1 and calicheamicin gamma 1I.: origin of their selectivities and "induced fit" mechanism. AB - This study addresses the DNA sequence recognition event of the enediyne antibiotics esperamicin A1 and calicheamicin gamma 1I by the use of synthetic DNA oligomers, salt effects, and circular dichroism studies. The results reported here provide several important insights: (1) esperamicin A1 requires a purine/pyrimidine trimer in host DNA for favorable interaction, (2) the sequence selectivity of esperamicin C is an origin of esperamicin A1 and calicheamicin gamma 1I selectivities, (3) in the target recognition by esperamicin C, its total structure and hydrophobicity are important, and (4) the binding of hydrophobic esperamicin to DNA duplex induces dehydration and conformational change of the host DNA. The specific sequence recognition process of esperamicin/calicheamicin has been discussed. PMID- 8485140 TI - Lipoprotein(a) binds to human platelets and attenuates plasminogen binding and activation. AB - Lipoprotein(a) [Lp(a)] is a unique lipoprotein consisting of a low-density lipoprotein moiety (LDL) covalently linked to apoprotein(a). Previous work has demonstrated that Lp(a) can compete with plasminogen (PGN) for binding to endothelial and mononuclear cells and can inhibit PGN activation in cell-free systems. We have assessed the binding of Lp(a) to platelets and the influence of binding on the activation of PGN by tissue-type plasminogen activator (t-PA) in this system. In direct binding experiments, Lp(a) bound specifically, saturably, and reversibly to platelets with an estimated apparent Kd of 0.20 microM. Scatchard analysis revealed a single class of binding sites with 81,000 +/- 22,000 particles of Lp(a) bound at saturation. Interestingly, Lp(a) bound to a similar extent to thromboasthenic platelets. Activation of platelets with ADP or thrombin reduced Lp(a) binding capacity by approximately 50% without changing affinity. Lp(a) also inhibited the binding of PGN to platelets with an IC50 of approximately 0.23 microM. Over a similar concentration range, LDL did not inhibit PGN binding to platelets. In addition, Lp(a) inhibited PGN binding to plasmin-treated platelets with an IC50 of approximately 0.2 microM. Kinetic experiments demonstrated that Lp(a) acted as a competitive inhibitor of PGN activation by t-PA on the platelet surface, with an estimated Ki of 0.49 microM. In the presence of platelets, Lp(a) decreased the kcat/Km for t-PA by 3-fold, owing primarily to an increase in the Km of t-PA for PGN. In contrast, LDL did not alter the kinetics of PGN activation by t-PA on the platelet surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485141 TI - Aggregation of phospholipid vesicles by a chimeric protein with the N-terminus of annexin I and the core of annexin V. AB - A chimeric protein was produced with the N-terminal domain (amino acids 1-45) of annexin I and the core of annexin V (amino acids 19-320). This protein, annexin IN-VC, has a similar Ca2+ requirement for binding to phospholipid bilayers of 20% phosphatidylserine (PS)/80% phosphatidylcholine (PC) as annexin V. In contrast to annexin V, this protein has a strong potency to aggregate phospholipid vesicles as is shown by turbidimetric measurements and cryo-electron microscopy. Ellipsometry was employed to study quantitatively the phenomenon of phospholipid vesicle adhesion to annexin IN-VC bound to a planar phospholipid bilayer. The amount of phospholipid vesicles bound by annexin IN-VC on the planar bilayer is proportional to its surface coverage and can be inhibited by coadsorption of annexin V on the planar bilayer or by shielding the phospholipid surface of the vesicles with blood coagulation factor Va. Annexin IN-VC, like annexin V, does not bind to pure PC bilayers, but its adsorption on anionic phospholipid bilayers brings about the capacity to bind pure PC vesicles. This suggests that annexin IN VC generates or exposes after binding to anionic phospholipids another phospholipid binding site, that differs from the annexin V phospholipid binding site. Collectively, the data suggest that two-dimensional cluster formation of annexin IN-VC on a bilayer with anionic phospholipids is involved in vesicle adherence. PMID- 8485142 TI - The role of protein charge in protein-lipid interactions. pH-dependent changes of the electrophoretic mobility of liposomes through adsorption of water-soluble, globular proteins. AB - The role of electrostatics in the adsorption process of proteins to preformed negatively-charged (phosphatidylcholine/phosphatidylglycerol) and neutral (phosphatidylcholine) liposomes was studied. The interaction was monitored at low ionic strength for a set of model proteins as a function of pH. The adsorption behavior of trypsin inhibitor (pI = 4.6), myoglobin (pI = 7.4), ribonuclease (pI = 9.6), and lysozyme (pI = 10.7) with preformed liposomes was investigated, along with changes in the electrophoretic mobility of liposomes through the adsorption of charged proteins. Mean protein charge was determined by acid/base titration. Significant adsorption of the proteins to negatively-charged liposomes was only found at pH values where the number of positive charge moieties exceeds the number of negative charge moieties on the protein by at least three charge units. Negligible adsorption to liposomes composed of zwitterionic lipids was observed in the pH range tested (4-9). The absolute value of the electrophoretic mobilities of negatively-charged, empty liposomes decreased after adsorption of positively-charged proteins. With increasing protein to phospholipid ratio, the drop in the electrophoretic mobility leveled off and reached a plateau; protein adsorption profiles showed a similar shape. Analysis of the data demonstrated that neutralization of the liposome charge due to the adsorption of the positively-charged proteins is the controlling factor in their adsorption. The plateau level reached depended on the type of protein and the pH of the incubation medium. This pH dependency could be ascribed to the mean positive charge of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485143 TI - Dimethyl methylphosphonate (DMMP): a 31P nuclear magnetic resonance spectroscopic probe of intracellular volume in mammalian cell cultures. AB - Dimethyl methylphosphonate (DMMP), when added to a suspension of erythrocytes, has been reported to have a lower frequency chemical shift inside of cells than outside. This work further investigates the same phenomenon in hollow-fiber bioreactor cultures of six mammalian cell lines and describes the application of DMMP as a measure of intra- versus extracellular volumes in mammalian cell cultures. No toxic effects of the DMMP were observed at the concentrations used here. The dependence of the shift of intracellular DMMP on intracellular protein content was shown to be similar for cultured mammalian and red blood cells. Also consistent with shifts in erythrocytes, an increase in the intracellular protein concentration due to a reduction in cultured cell volume increased the magnitude of the shift to lower frequency. Longitudinal relaxation (T1) values for intra- and extracellular DMMP were measured so that partially saturated DMMP peaks in 31P NMR spectra of mammalian cell cultures can be corrected to give the relative volumes of the intra- and extracellular compartments; this information provides a relative measure of culture growth. Intracellular volume measured by this method can also be used to quantify intracellular metabolites such as ATP during the growth of the culture. To explore the mechanism behind the intracellular shift, we have also addressed the three possible contributions to the chemical shift of DMMP: hydrogen-bonding interactions, magnetic susceptibility, and ionic strength. Data is presented which eliminates the latter two mechanisms and strongly supports the hypothesis that the observed intracellular shift is due to a reduction in hydrogen bonding between water and DMMP in the cytoplasm. PMID- 8485144 TI - Characterization of the folate-dependent mitochondrial oxidation of carbon 3 of serine. AB - The folate-dependent catabolism of serine was studied in intact rat liver mitochondria and soluble extracts from sonicated mitochondria. Formate and CO2 are both known to be products of the mitochondrial oxidation of carbon 3 of serine. The present work tests the proposal [Barlowe, C. K., & Appling, D. R. (1988) Biofactors 1, 171-176] that carbon 3 of serine is first oxidized to 10 formyltetrahydrofolate, which can be either oxidized to CO2 or converted to formate. Oxidation of carbon 3 of serine to formate and CO2 was shown to be dependent on the respiratory state of the mitochondria. Formate production was greatest in state-3 (actively respiring) mitochondria and lowest in uncoupled mitochondria. In contrast, CO2 production was greatest in uncoupled mitochondria and lowest in respiratory-inhibited mitochondria. Formate production appeared to be favored when high concentrations of NADP+ and ADP were present, but there was no clear correlation between the NADP+:NADPH redox state and CO2 production. In soluble mitochondrial extracts, CO2 production depended on NADP+ and tetrahydrofolate, whereas formate production required ADP in addition to NADP+ and the reduced folate cofactor. Unlike CO2 production, however, formate production showed a complete dependence on a polyglutamylated form of the folate cofactor. These experiments support the proposed folate-mediated serine oxidation as a major pathway for the flux of one-carbon units through mitochondria. PMID- 8485145 TI - Expression, purification, and characterization of the Drosophila kinesin motor domain produced in Escherichia coli. AB - The Drosophila kinesin heavy-chain gene was truncated to obtain the N-terminal 401 amino acid motor domain (designated K401) containing both the microtubule and ATP binding sites. The plasmid construct with the truncated kinesin gene was used to transform Escherichia coli. After induction, K401 was expressed as soluble kinesin protein at high levels and purified to homogeneity in milligram quantities. The purified protein was active and behaved as native kinesin with respect to its steady-state kinetic properties: K401 demonstrated a very low ATPase activity (kcat = 0.01 s-1) which was stimulated approximately 1000-fold by the addition of microtubules (kcat = 10 s-1; K0.5,MT = 0.9 microM tubulin; Km,ATP = 31 microM). Like native kinesin, K401 when purified contained ADP tightly bound at its active site, and the release of ADP from the active site occurred at a rate equal to the steady-state ATPase kcat. Active-site measurements using [alpha 32P]ATP demonstrated a stoichiometry of one ATPase site per K401 molecule. Like native kinesin, K401 can also hydrolyze MgGTP, and in the presence of microtubules, the rate of hydrolysis was increased dramatically from 0.03 to 16 s 1 (K0.5,MT = 2 microM tubulin; Km,GTP = 3.5 mM). These results establish that an active kinesin motor domain can be bacterially expressed and that this domain, the N-terminal 401 amino acids of the Drosophila kinesin heavy chain without light chains or additional eukaryotic factors, has full catalytic activity with microtubules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485146 TI - Glucose metabolism in Escherichia coli and the effect of increased amount of aldolase. AB - We present a comparative study of Escherichia coli with normal and increased amounts of fructose-1,6-bisphosphate aldolase. Most experiments employed a resting cell system involving a high cell density (so as to obtain the soluble pool by direct extraction) and anaerobic incubation in the presence of chloramphenicol. Glucose use is linear with time with a rate ca. half of that in growth, fermentation is almost quantitative, and metabolite concentrations reach a quasi steady state. Increased amount of aldolase had little effect on glucose flux; fructose-1,6-P2 concentration decreased by ca. one-third, and the extent of equilibration of its two halves, measured by a dismutation procedure on samples taken during metabolism of [6-14C]glucose, increased from 0.33 [(cpm in C1 3)/(cpm in C1-6)] to 0.43. Using the simplest model, that increased amount of aldolase does not perturb net flux or later metabolites, together with the steady state rate equations for aldolase and triose-P isomerase, we show that the results with resting cells fit with the extra enzyme being fully active, and do not necessitate special assumptions concerning a glycolytic complex, metabolite compartmentation, or secondary mechanisms assuring high metabolite concentration. However, the fit does require that the measured Vmax values substantially underestimate the actual ones. Calculation also shows that the forms of the predicted curves--and hence the fit with experimental data--of fructose-1,6-P2 concentration and labeling as a function of the amount of aldolase are highly dependent on glyceraldehyde-3-P concentration but independent of the kinetic parameters of aldolase. PMID- 8485147 TI - POU domain transcription factors. PMID- 8485148 TI - Two developmentally regulated mRNAs encoding actin-binding proteins in Physarum polycephalum. AB - A cDNA library from amoebae of Physarum polycephalum was screened by differential hybridization. Two clones contained inserts for mRNAs present in amoebae and absent in plasmodia. The LAV3-4 cDNA encodes a 402 aa protein (ABP-46) that shows sequence similarity to the actin binding site in the N-terminal region of the alpha-actinin family. The LAV3-5 cDNA is 76% identical to the Dictyostelium actin bundling protein, which cross-links and stabilizes actin filaments in amoebal filopodia. PMID- 8485149 TI - Structural analysis of an extremely long 5'-noncoding region of rat brain argininosuccinate lyase mRNA: presence of multiple B1 repeats and multiple upstream AUG codons, and a possibility of translational control. AB - The present detailed analysis of the sequence of the extremely long (967 bp) 5' noncoding region of a rat brain argininosuccinate lyase cDNA clone, reveals several features of interest. Multiple copies of partial and inverted (antisense) B1 repeats and multiple upstream ATG codons are present in the region, which suggests a possibility of translational control of the argininosuccinate lyase gene expression in rat brain. PMID- 8485150 TI - Cloning and characterization of an alpha-amylase gene from Streptomyces lividans. PMID- 8485151 TI - Expression and characterization of a recombinant maize CK-2 alpha subunit. AB - CKIIB, one of the CK-2 like enzymes which have been isolated from maize, has been shown to be a monomeric enzyme that cross-reacts with anti CK-2 alpha specific antibodies suggesting a possible relationship between the two proteins (Dobrowolska et al. (1992) Eur. J. Biochem. 204, 299-303). In order to support the immunological data also by biochemical and biophysical experiments the availability of a recombinant CK-2 alpha from maize was a prerequisite. A maize cDNA clone of maize CK-2 alpha was expressed in the bacterial strain BL21 (DE3). The recombinant protein was purified to homogeneity; its molecular mass on one dimensional SDS PAGE was estimated to be 36.5 kDa. The calculated molecular mass according to the amino acid composition is 39,228 Da (332 amino acids). The recombinant maize CK-2 alpha (rmCK-2 alpha) exhibited mostly the same properties as the recombinant human CK-2 alpha (rhCK-2 alpha). In several respects it behaved differently from CKIIB, thus supporting the notion that either CKIIB is encoded by another gene or it undergoes extensive posttranscriptional and/or posttranslational alterations. Three observations in particular disprove any close relatedness between CKIIB and rmCK-2 alpha, namely: (a) the phosphorylation of calmodulin by CKIIB is dramatically stimulated by polylysine, whereas polylysine inhibits rather than stimulating the phosphorylation of calmodulin by rmCK-2 alpha (and by rhCK-2 alpha). (b) Addition of rhCK-2 beta has no significant influence on the stimulation of the calmodulin phosphorylation by CKIIB whereas in the case of rmCK-2 alpha and rhCK-2 alpha addition of rhCK-2 beta is required for optimal stimulation by polylysine. (c) CKIIB does not self assemble with rhCK-2 beta to form a high molecular mass complex as it is demonstrated for rmCK-2 alpha. PMID- 8485152 TI - Structure and conformation of N4-hydroxycytosine and N4-hydroxy-5-fluorocytosine. A theoretical ab initio study. AB - Optimal molecular geometries and molecular energies were obtained for N4 hydroxycytosine and its 5-fluoro congener with the use of the theoretical ab initio quantum mechanical calculations within the Self Consistent Field method corrected for the electron correlation effects by the second-order Many Body Perturbation Theory (SCF + MBPT(2)). The 6-31G Gaussian basis set was employed. Several tautomeric and rotameric forms were considered. For N4-hydroxycytosine and N4-hydroxy-5-fluorocytosine the imino tautomer (in the conformation syn relatively to the N3-nitrogen atom) appeared to be the most stable form. The imino tautomer of N4-hydroxy-cytosine in the anti rotameric form is by 12.8 kJ mol-1 less stable than the imino-syn form. The 5-fluoro substituent raises the energy difference between the syn and anti rotamers up to 38.5 kJ mol-1. The potential energy barrier for the syn-anti rotation in the imino form of N4 hydroxycytosine is estimated to be about 180 kJ/mol. The results presented in this paper suggest that the syn-imino and anti-imino forms can be treated as two structural isomers that do not interconvert at temperatures relevant to biochemical conditions. The theoretical results also show that the amino tautomeric forms do not compete with the imino forms in the gas-phase and in non polar and weakly-polar environment. In a polar environment (e.g., in aqueous solutions), however, one may expect an increased population of the amino forms. Qualitatively, the results of the present study agree well with the available experimental and theoretical data for N4-hydroxycytosine and some of its derivatives. The implications of the present study are discussed in relation to the molecular mechanisms of mutagenesis caused by NH2OH and of enzyme (thymidylate synthase) inhibition by N4-hydroxydeoxycytidine monophosphate. PMID- 8485153 TI - Protection of mRNA against nucleases in cytoplasmic extracts of mouse sarcoma ascites cells. AB - The mRNA present in extracts of mouse sarcoma 180 (S-180) ascites cells is relatively resistant to degradation when compared to added tracer ribosomal RNA. Deproteinized mRNA added to the extract is about as resistant as the endogenous mRNA, an indication that the protection is not due to any protein present in the endogenous mRNP structure. A major determinant of protection lies at the 5' end of RNA chains, where the presence of a triphosphate or a cap enhances the stability of mRNA transcripts. Addition of poly(A) to a capped transcript had little effect on stability. Stabilization by the cap structure is apparently not due to association of transcripts with a cap-binding protein. The discrimination in RNA decay rates appears to be based on interaction of the different RNA species with an exonuclease, which represents the predominant ribonuclease activity in the extract. Other major cytoplasmic nucleases are suppressed by an RNase inhibitor that is present in excess. PMID- 8485154 TI - A 5' exoribonuclease from cytoplasmic extracts of mouse sarcoma 180 ascites cells. AB - An exonuclease that appears to represent the predominant nuclease activity in cytoplasmic extracts of sarcoma 180 ascites cells has been partially purified and characterized. The enzyme attacks RNA chains in a 5' to 3' direction, and releases 5'-mononucleotides. The initial cleavage, however, can occur at either the first, second and probably third phosphodiester linkage in some RNAs. The enzyme attacks transcripts terminated with a 5'-triphosphate more slowly than those with a 5' monophosphate, and releases a compound larger than GTP from transcripts that begin with a pppG. Capped transcripts are cleaved at least as readily as those with a 5'-P, yielding a compound larger than 7mGpppGm. The occurrence of an such an exonuclease capable of attacking capped RNAs would make it possible for mammalian cells to initiate mRNA degradation by a 5' exonucleolytic mechanism. PMID- 8485155 TI - Molecular cloning and sequencing of the murine alpha-2-macroglobulin receptor cDNA. AB - We have molecularly cloned and sequenced the mouse alpha-2-macroglobulin receptor cDNA. The cDNA contained 14849 bases with one large open reading frame of 4545 codons which is one more than in the corresponding human cDNA. Comparison of the predicted mouse and human receptor proteins revealed the very conserved nature of this receptor with an overall amino acid identity of more than 97%. A dramatic example of this is the presence of 331 cysteine residues predicted in the mouse protein, of which 327 are positionally conserved relative to human. PMID- 8485156 TI - Primary structure of Tetrahymena hemoglobins. AB - The primary structure of hemoglobins of Tetrahymena thermophila and T. pyriformis was determined by peptide and cDNA sequence analysis. Their sequences were 83.5% identical to each other and homologous to other protozoan and cyanobacteria hemoglobins, but not to proteins of the globin family. An intron was not present in the T. thermophila hemoglobin gene. PMID- 8485157 TI - Characterization of two sheep insulin-like growth factor II cDNAs with different 5'-untranslated regions. AB - We have isolated two sheep IGF-II clones which have the same coding regions but have different 5'-untranslated regions. There is no homology between these 5'-UTR sequences which are homologous to exons 5 and 6 of the human IGFII gene. In humans these exons are transcribed only during fetal development, but in the sheep these transcripts were detected up to 28 weeks after parturition. The sizes of the sheep IGF-II mRNA transcripts are the same as those observed for the human gene, suggesting structural and transcriptional similarity between the human and sheep IGF-II genes. The sheep could therefore be a good model system in which to study IGF-II expression. PMID- 8485158 TI - cDNA sequence for bovine biglycan (PGI) protein core. AB - The nucleotide sequence of the protein core for bovine aortic smooth muscle cell biglycan was determined using recombinant DNA technology. Analysis of the deduced amino acid sequence for bovine biglycan revealed a striking homology, 94.6% and 95.7%, to human and rat biglycan, respectively. The bovine biglycan protein core has four potential O-linked and two potential N-linked glycosylation sites and is composed of 11 leucine-rich repeat units. PMID- 8485159 TI - Characterization of the gene for seminalplasmin, a secretory protein of the bovine seminal vesicle. AB - As part of an attempt to understand the androgen-regulated expression of seminalplasmin, a major basic protein of bovine seminal vesicle secretion, we have characterized the bovine seminalplasmin gene. The compact gene of approximate size of 2.1 kb is organized in four exons and three introns. Regulatory sequences involved in regulation of transcription could not be identified by simple sequence homologies. A putative promoter element TATAA is located 29 bp upstream of exon 1. PMID- 8485160 TI - Molecular cloning and sequence of two cDNAs for human subunit c of H(+)-ATP synthase in mitochondria. AB - Two cDNAs encoding different signal peptides (61 and 66 amino acid residues) and the same mature protein have been cloned from a human cDNA library with a rat subunit c cDNA. The amino acid sequence of the mature human subunit c of mitochondrial H(+)-ATP synthase was completely identical with those of the mature bovine, sheep and rat subunit c. PMID- 8485161 TI - A Plasmodium vinckei cysteine proteinase shares unique features with its Plasmodium falciparum analogue. AB - The gene encoding a cysteine proteinase of the murine malaria parasite Plasmodium vinckei has been identified and characterized. The gene encodes a papain-family proteinase that shares unique features with a previously described P. falciparum cysteine proteinase. We hypothesize that both enzymes mediate the hydrolysis of hemoglobin, and perhaps other Plasmodium-specific functions. PMID- 8485162 TI - The isolation and characterization of a Drosophila gene encoding a putative NAD dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase. AB - Mammalian NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase-5,10 methenyltetrahydrofolate cyclohydrolase is a bifunctional mitochondrial enzyme expressed in most established cell lines but only in developing normal tissues. We report the cloning and molecular characterization of a Drosophila gene (DNMDMC) that encodes a protein with 56% identity to the mammalian bifunctional protein. Like the mammalian bifunctional proteins, the Drosophila protein contains a putative mitochondrial targeting sequence and its transcripts are expressed in developing tissues. Unlike its mammalian homologs, DNMDMC is expressed at high levels in adult tissues. DNMDMC maps to polytene chromosome band 85C, is encoded in three exons, and is closely flanked by two additional genes. PMID- 8485163 TI - Sequence of a gene coding for a cytoplasmic alcohol dehydrogenase from Kluyveromyces marxianus ATCC 12424. AB - Using a Saccharomyces cerevisiae ADH1 probe, a gene coding for a cytoplasmic alcohol dehydrogenase from Kluyveromyces marxianus ATCC 12424 (formerly K. fragilis) has been cloned. This gene is able to restore alcoholic fermentation in an ADH-null strain of S. cerevisiae and its encoded protein shows strong similarity with other yeast alcohol dehydrogenases (from S. cerevisiae, Schizosaccharomyces pombe and its close relative K. lactis). The product of the gene expressed in S. cerevisiae co-migrates on native gel with a K. marxianus ADH isozyme which is more active in cells growing on non-fermentable carbon sources than on glucose. This behaviour is in contrast with that of the two cytoplasmic ADH isozymes of K. lactis which are both more active in glucose-growing than in ethanol-growing cells. PMID- 8485164 TI - Ca2+ antagonists do not protect isolated perfused rat hepatocytes from anoxic injury. AB - Ca2+ antagonists were studied during anoxia in perfused isolated rat hepatocytes. Cytosolic free calcium (Ca2+i) was measured with aequorin. Anoxia was induced for 2 h by saturating the perfusate with 95% N2/5+ CO2. Anoxia increased Ca2+i in two distinct phases reaching a maximum of 1.5 microM. The increase in Ca2+i was caused by Ca2+ influx from the extracellular fluids because the main Ca2+i surge was totally abolished in Ca(2+)-free media. LDH release increased 6-fold during the second hour of anoxia, but when Ca2+ was removed from the perfusate during the anoxic period, LDH rose only 2.7-fold. Ca2+ antagonists (10(-7) to 10(-5) M) did not prevent the increase in Ca2+i and the rise in LDH release. On the contrary, high concentrations (10(-6) and 10(-5) M) of the blockers nifedipine and diltiazem significantly increased anoxic cell injury. The observation that the increase in LDH and the rise in Ca2+i were not suppressed by Ca2+ antagonists suggests that (i) Ca2+ antagonists protect the whole liver from anoxic injury by acting on cells other than parenchymal cells; (ii) the influx of Ca2+ responsible for the massive increase in hepatocyte Ca2+i evoked by anoxia did not take place through voltage-sensitive Ca2+ channels but must have occurred via the Na(+)-Ca2+ antiporter operating in the reverse mode (Ca2+ influx vs. Na+ efflux), and (iii) high concentrations of Ca2+ antagonists may be deleterious to the parenchymal cells of the liver. PMID- 8485165 TI - Binding sites for short-term glycated albumin on peritoneal cells of the rat. AB - The interaction of in vitro short-term glycated rat serum albumin with rat peritoneal cells (40% macrophages) was investigated. Using 125I-labeled albumins the following results were obtained. Glycated albumins showed a binding reaction at 4 degrees C, which appeared to reach equilibrium within 2 h. The concentration dependent binding of glycated albumin showed saturation. Binding data evaluated for glycated albumin using the Sips equation are: average association constant Ko = 3.15 x 10(7) M-1 with a heterogeneity index of a = 0.8 and 1.12 x 10(4) binding sites per cell. Such binding sites were identified in 40% of the peritoneal cell preparations studied. Native albumins, maleylated albumin, chondroitinsulfates, polylysine, lysine, fructose, glucose and hexitol-lysine could not compete with radio-labeled glycated rat albumin for its binding site on peritoneal cells. Effective competitors were glycated human serum albumin, glycated polylysine and fructose-lysine. Although the contamination with minute amounts of advanced glycosylation end products (AGE) could not be excluded, short-term glycated albumin was found to be bound to membranes of peritoneal phagocytotic cells by fructose-lysine specific proteins, whose approximately defined molecular masses of 290 kDa are distinct from hitherto described binding proteins for AGE- and aldehyde-modified proteins or for the scavenger receptors. PMID- 8485166 TI - Identification and characterization of nuclear calmodulin-binding proteins of Saccharomyces cerevisiae. AB - Nuclear calmodulin-binding proteins of the yeast Saccharomyces cerevisiae were investigated. The soluble fractions after serial treatments of the isolated nuclei with buffers containing the nonionic detergent NP-40 (F1), 0.5 M KCl (F2) and 2.0 M KCl (F3) in this order, and the residual proteins (F4) were obtained. The calmodulin-binding proteins of the nucleus and nuclear subfractions were identified using the gel overlay method using 125I-calmodulin. Each subnuclear fraction contained a large number of components that bound calmodulin in a Ca(2+) dependent or -independent manners. The calmodulin-binding proteins were isolated from F1 and F2 subnuclear fractions by affinity chromatography. The affinity purified proteins bound calmodulin in a Ca(2+)-dependent manner when analyzed using the gel overlay method. The major calmodulin-binding components of F1 were 44, 42, 36, 32 and 29 kDa proteins, and those of F2 were 200, 100, 40, 42, 36, 34 and 32 kDa proteins. The isolated proteins also contained several Coomassie-blue stained proteins that did not bind calmodulin and, therefore, may represent the proteins associated with the calmodulin-binding proteins. Antisera raised against the affinity-purified preparation of F1 and F2 recognized almost all of the calmodulin-binding proteins present in the fraction and several other proteins of the nucleus. The presence of Ca(2+)-dependent protein phosphatase (type 2B) in the nucleus was demonstrated by Western blotting. The enzyme was localized predominantly in F1 and F4. PMID- 8485167 TI - Thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase, enhances c-fos expression but antagonizes vacuole formation of human hepatoma cells induced by teleocidin. AB - Teleocidin, a phorbol ester-type tumor promoter, enhanced actin redistribution, vacuole formation and c-fos expression of PLC/PRF/5 hepatoma cells. This tumor promoter also inhibited calcium mobilization induced by epidermal growth factor (EGF). Thapsigargin, a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase, elevated cytosolic calcium, enhanced c-fos expression and antagonized the vacuole formation induced by teleocidin without interfering with actin redistribution and Lucifer yellow uptake. On the other hand, a calcium ionophore ionomycin elevated both cytosolic Ca2+ and c-fos mRNA but could not antagonize the vacuole formation induced by teleocidin. From these results it was speculated that the Ca2+ leak from the endoplasmic reticulum rather than the elevation of cytosolic Ca2+ appeared to be responsible for the specific inhibition of vacuole formation by thapsigargin. PMID- 8485168 TI - Differential effects of the phorbol ester TPA on DNA-mediated transfection in a variety of cell lines. AB - The efficiency of stable gene transfer and expression in NIH3T3 cells has been shown to be significantly enhanced by a brief treatment with the phorbol ester tetradecanoylphorbol 12,13-acetate (TPA) immediately following calcium-phosphate transfection. Several lines of evidence indicated that this effect was mediated through protein kinase C activation. These studies were expanded to determine whether this was a consistent and widespread phenomenon among other cell lines. The efficiency of transfection in two other established fibroblast lines, LMtk- and 2A3 3T3, was unaffected by TPA treatment, and primary human foreskin fibroblasts were similarly unaffected. Transfection was inhibited by TPA treatment in the transformed cell lines EJ and HeLa. Protein kinase C enzyme assays indicated that TPA causes a translocation of the enzyme from cytosol to membrane in both NIH3T3 and EJ cells, suggesting that the PKC translocation event does not account for the TPA effect on transfection. The TPA-mediated inhibition of transfection in EJ cells was not blocked by sphingosine, suggesting that this phenomenon is unrelated to PKC activation. The results suggest that TPA treatment may either enhance, inhibit, or have no effect on transfection, depending on the cell line. PMID- 8485169 TI - Hexose metabolism in pancreatic islets: time-course of the oxidative response to D-glucose. AB - The time-course for the generation of 3HOH from D-[5-3H]glucose and for the production of 14CO2, 14C-labelled acidic metabolites and radioactive amino acids from D-[3,4-14C]glucose, D-[2-14C]glucose and D-[6-14C]glucose was monitored, over 60 to 120 min incubation, in both rat pancreatic islets and parotid cells exposed to a low or high concentration of the hexose. In islets stimulated by D glucose, a progressive increase in the oxidation rate of glucose-derived acetyl residues was observed. Such a phenomenon was not observed in islets exposed to a low concentration of D-glucose, concerned specifically the oxidation of acetyl residues in the Krebs cycle as distinct from their generation in the reaction catalyzed by pyruvate dehydrogenase, and failed to occur in parotid cells. It is concluded that the increase in the oxidation rate of glucose-derived acetyl residues found in pancreatic islets represents an unusual phenomenon not encountered in other cell types and specifically regulated in terms of its time course, concentration dependency and relationship to other oxidative events. PMID- 8485170 TI - Inhibition of stimulated bone resorption in vitro by TIMP-1 and TIMP-2. AB - Recombinant human TIMP-1 and TIMP-2 (tissue inhibitors of metalloproteinases) inhibited bone resorption induced by either parathyroid hormone or 1,25 dihydroxyvitamin D3 in cultured neonatal mouse calvariae. The inhibition was reversible, dose-dependent and complete at 1 microgram/ml inhibitor concentration. TIMP-2 was more potent than TIMP-1. TIMP-1 and TIMP-2 also inhibited basal bone resorption. Neither metalloproteinase inhibitor affected protein synthesis, DNA synthesis, the PTH-enhanced secretion of beta glucuronidase or the spontaneous release of lactate dehydrogenase. These results suggest that endogenous TIMPs play a central role in regulating both physiological and pathological bone resorption. PMID- 8485171 TI - Increase of adipose differentiation by hypolipidemic fibrate drugs in Ob 17 preadipocytes: requirement for thyroid hormones. AB - The action of hypolipidemic fibrate drugs (HFD) (clofibrate, bezafibrate, fenofibrate) was studied in relation to thyroid hormone (TH) action in the TH sensitive Ob 17 preadipocyte cells which require an early presence of TH for terminal differentiation. HFD markedly amplified the adipose differentiation and the development of several lipogenic enzymes, thus accelerating their appearance after cell growth arrest. This amplifying action could be obtained whatever the time of drug addition to the cells and required the continuous presence of the drug. HFD action was strictly dependent on the presence of TH. Within the active concentration range (0.01-0.25 mM) in serum-containing medium, HFD moderately down-modulated the nuclear TH receptor level (and c-erb alpha mRNA abundance), this being additive to the known maximal but partial down-regulation provoked by TH. The results strengthen the TH obligatory role for Ob 17 cell differentiation and give arguments against a TH-like role of HFD. In this cell line, HFD mainly behave as amplifiers for the expression of lipogenic phenotypes in already committed cells. PMID- 8485172 TI - Unilateral nephrectomy selectively stimulates phospholipase D in the remaining kidney. AB - The activation of phospholipase D in the kidney could be detected in vivo in rats treated with ethanol by the accumulation of phosphatidylethanol. Unilateral nephrectomy stimulated the activity of phospholipase D in the remaining kidney as indicated by an increase in the level of phosphatidylethanol. A significant increase in phosphatidylethanol level was observed as early as 5 min after contralateral nephrectomy and peak accumulation (200% of control) was observed after 15 min. The phosphatidylethanol level decreased again to the basal level after 2 h. The accumulation of phosphatidylethanol was specific for kidney and the product was localized primarily in the cortex. Phospholipase D activity in kidney cortical slices from untreated rats was stimulated in vitro by plasma obtained from unilaterally nephrectomized rats, indicating that circulating factors in the plasma are responsible for the activation of phospholipase D. The phospholipase D activation by plasma from uninephrectomized animals was selectively inhibited by the tyrosine kinase inhibitor genistein, but not by the protein kinase C inhibitor H7. It is concluded that phospholipase D activity is stimulated as an early signal transduction event in compensatory kidney growth. PMID- 8485173 TI - Development of an antiserum to rat-brain A1 adenosine receptor: application for immunological and structural comparison of A1 adenosine receptors from various tissues and species. AB - An antiserum was developed in a rabbit against rat-brain A1 adenosine receptor. This antiserum recognized the denatured form of the purified rat-brain A1 adenosine receptor in immunoblot analysis and the native form of the receptor in the immunoprecipitation analysis. Immunoblot analysis of unpurified or purified adenosine receptor preparations from rat-brain membranes revealed a major immunoreactive band at a position of molecular mass of approx. 35 kDa, which corresponds to the position of purified rat-brain A1 adenosine receptor. Although A1 adenosine receptors from other rat tissues such as testis and adipocyte were also found to be immunoreactive with this antiserum by immunoblot analysis, purified human-brain A1 adenosine receptors showed a poor reactivity with this antibody. The order of the relative immunoreactivity of these A1 adenosine receptors with the antiserum was found to be brain > adipocyte > or = testis. Moreover, the immunoreactivity of these receptors significantly increased after these receptor preparations were deglycosylated by endoglycosidase F. After the deglycosylation, no significant differences in both the immunoreactivity and molecular mass among these receptor preparations were found on the immunoblot. These results suggest that the differences in the molecular mass or immunoreactivity among the A1 adenosine receptor preparations from three rat tissues were mainly due to the difference of sugar moiety present in each receptor molecule. These data are the first to provide analyses of immunological characteristics of A1 adenosine receptors from different tissues and species. PMID- 8485174 TI - Who writes for GNJ? Plans for an authors' survey. PMID- 8485175 TI - Exposure to human immunodeficiency virus in the endoscopy setting: a personal experience. AB - Physicians and staff in the endoscopy unit are seeing an increasing number of patients who are human immunodeficiency virus positive or who have acquired immunodeficiency syndrome. Despite the practice of universal precautions, exposure can occur very easily. It happened to me. This article describes some of the details of my experience in the hope that it will increase awareness and promote the use of better precautions in all hospital settings. PMID- 8485176 TI - Infection control aspects for office endoscopy. AB - While preventing cross-infection has always been important, the current epidemic of human immunodeficiency virus has brought about a greater awareness that infection control standards should be the same regardless of the practice setting. This article discusses infection control practices in office endoscopy including cleaning of endoscopes and the issues surrounding disposable and nondisposable accessories. Staff safety and government agency regulations are also reviewed. PMID- 8485177 TI - Budget for a research proposal. AB - As a result of the growing consumer demand to cut health care costs, employing institutions cannot be expected to finance research studies. Therefore, outside funding must be found. The proposal budget is critical to the success of a study. A reviewer can determine much about the principal investigator's ability to conduct the proposed study by scrutinizing the budget; therefore, the budget should not be treated as an afterthought. A good budget consists of three separate parts: the budget, the budget explanation, and a section in the narrative devoted to the budget. Ask for the funds that are needed to complete the study and then justify the need. The goal of a good budget is to answer the reviewers' questions before they occur. PMID- 8485178 TI - Orally administered gallbladder therapeutic agents, Part 1: Chenix (chenodeoxycholic acid, CDCA). AB - Chenix is an orally administered gallstone solubilizer that reduces biliary cholesterol in the bile acid pool, which in effect helps to dissolve floating radiolucent cholesterol gallstones. Chenix is an agent used to treat cholesterol gallstones in the patient with a higher than average risk for surgical intervention for the removal of gallstones. PMID- 8485179 TI - Foreign body ingestion and removal in adults. PMID- 8485180 TI - [Thermodynamic and spectroscopic study of complex formation of dipeptides with dimethyl sulfoxide in their aqueous solutions]. AB - Peculiarities of intermolecular interactions in water-dimethylsulfoxide solutions of dipeptides-glycyl-glycine, beta-alanyl-glycine, beta-alanyl-beta-alanine, DL alpha-alanyl-DL-alpha-alanine, DL-alpha-alanyl-DL-valine-were analysed on the basis of thermodynamic characteristics and data on IR-spectra. Dimethylsulfoxide additions were shown to cause destruction of peptide associates present in aqueous solutions due to the formation of stronger bonds "peptide-DMSO". The existence of complexes between dimethylsulfoxide and beta-alanyl-glycine, beta alanyl-beta-alanine, DL-alpha-alanyl-DL-alpha-alanine was found. The mechanism of their formation was determined by the dipeptide structure. PMID- 8485181 TI - [Difference in DNA enthalpies in the helical and coiled states near 0 K]. AB - On the basis of experimental data of DNA heat capacity in a wide range of temperatures the fundamental characteristics of DNA-H(0)0-the enthalpy of helix coil transition at 0(0)K were estimated. H(0)0 = 8.41 +/- 1.6 kJ/MBP. It was shown that a deviation from Nernst theorem (resulting from metastability of the system) was not obtained within the range of experimental error. PMID- 8485182 TI - [Preparation and study of Langmuir films of nucleic acid and octadecylamine complexes]. AB - Formation conditions of langmuir films of nucleic acids (DNA and poly-U) octadecylamine complexes are determined. Successive transfer of the monolayers of these complexes from the aqueous subphase surface to solid substances (quartz, silicon) is carried out. The structure of multilayer langmuir films of nucleic acid-octadecylamine complexes is studied by small angle X-ray scattering, ellipsometry and UV-spectroscopy. The produced films are shown to have high lamellar orderliness with the multilayer structure period D = 57.0 A. A scheme of the realized structure of these films is proposed in which the nucleic acids are located between octadecylamine bilayers. A suggestion is discussed based on similar results for poly-U and DNA containing langmuir films concerning possible untwisting of double helical DNA in the langmuir film of octadecylamine, as well as biological significance of the discovered phenomena. PMID- 8485183 TI - [Emergence of contraction waves on the surface of fertilized frog eggs under the effect of inositol triphosphate]. AB - It was shown that the injection of the membrane messenger-myo inositoltrisphosphate into frog eggs provokes the propagation of surface contraction waves. Such waves are not accompanied by the changes of membrane potential. We have analyzed the spatial-temporal characteristics of observed waves and have compared them with the data from models for diffusion and autocatalytic mechanisms of wave propagation. PMID- 8485184 TI - [Computer analysis of ultrastructural and functional parameters of rat liver mitochondria]. PMID- 8485185 TI - [Hysteresis properties of excitable membranes--the basis for neuronal memory]. AB - It is supposed that "fixed" membrane charges are spaced on protein lateral chain terminals and have limited ability to move with the chains. Interactions of the charges that are located on the opposite sides of the membrane depend on the membrane potential and can be described by a hysteresis volt-conformation characteristics with trigger transitions for one stable state to another. The value of the charges, that are shifted in the hysteresical loop limit, is close to the experimental data for gate currents. Possibility of interaction of chemoreceptive and electroexcitable mosaics of the neuron somato-dendrite membrane in eeg forming process is analysed. PMID- 8485186 TI - [Optimization of randomly organized distributive associative memory]. AB - Sub- and intersynapsal randomly placed mosaics of somato-dendritical membrane are regarded as a neuronal memory system. The first (linear) subsystem seems as a mean for access (addressing) to the second (nonlinear, hysteresis) one. An informative model is created and optimal relations are detected on the threshold, geometrical and temporal parameters of the synapse fields. The relations being settled transform the synapse field to associative memory with optimal distributive features. The reliability of such memory is equal to one of the holograms. PMID- 8485187 TI - [Recording, consolidation, and reproduction of information in the neuronal memory]. AB - The electroexcitable mosaic of neuron SD-membrane is considered to be a hysteresis medium: a set of bistable memory units (MU) that capture or give back the energy in state transitions. The consolidation is shown to be achieved by inactivation of a part of MU (which had lost their energy) by means of transit of their volt-conformative characteristics to the non-hysteresis form. The MU hysteresis features are the result of moderate mobility of the membrane charges. The consolidation results in immobilization of the charges. It seems that immobilization of gate charges is the same phenomenon. Great importance of time delay pertaining to this process is emphasized. The time delay and working point shift beyond the hysteresis loop limits into the hyperpolarization side ensures the non-destructive reading. PMID- 8485188 TI - [A method of mapping intracortical interactions during perception and reproduction of emotions]. AB - By a new method of mapping intracortical interaction participation of the cerebral cortical zones in the process of perception and mental reproduction of human emotional states was studied. At identification of emotions the maximum value of connections was found in the left cortical temporal area. At mental reproduction of emotional states the maximum value of connections was found predominantly in the frontal cortical areas and left temporal cortical zone. PMID- 8485190 TI - [Use of nonlinear dynamics methods for detecting and describing chaotic deterministic EEG components]. PMID- 8485189 TI - [Interneuronal functional connections in the canine sensomotor cortex]. AB - Multiple unit activity (MUA) of the sensomotor cortex was recorded from chronically implanted semimicroelectrodes in dogs. The spike trains of 6-8 neural units were selected from MUA. The character and temporal parameters of interneuronal functional connections were examined by the method of computerized cross-interval analysis. For this purpose the autocorrelation and cross-interval histograms were constructed. One of the main results was complete absence of symmetrical central peaks (shared input). The functional interrelations of selected neurons were characterized by unilateral and bilateral nonsymmetrical excitatory connections with short (1-10 ms), middle (10-80 ms) and late (80-2000 vs) delays. The peculiarities of these interneuronal connections are discussed. PMID- 8485191 TI - [Analysis of nonlinear dynamic states of the brain during different activation levels of it (studies in the high frequency EEG range of the rabbit)]. AB - With the use of the nonlinear analysis method the existence of the determinant chaotic high-frequency EEG component of the rabbits' brain cortex was shown. Its parameters depend on the brain area and reflect the functional state of the animal. PMID- 8485192 TI - [Averaged impulse activity in a neuronal network model]. AB - Every neuronal pool is proposed to contain identical neurons with identical interneuronal connections. A neuronal net containing two neuronal pools is considered. Two regimes are possible: 1) the asymptotically stable stationary solution of smooth equations system exists, the neuron pulses are periodical with different frequency in each pool; 2) the stationary sliding regime solution of smoothed equations exists. Periodical pulse train solution is impossible. The situation of "chaos" type is probable. PMID- 8485193 TI - [Studies of spatial relationship of various electrical processes of the human brain during their simultaneous registration]. AB - Results of investigations of spatiotemporal relationships for electrical processes of human brain, different in their frequency bands and simultaneously recorded from a number of brain zones intracerebrally or extracerebrally are reviewed. Spatiotemporal relationships for EEG and infraslow processes are significantly different. PMID- 8485194 TI - [Spatial-temporal coding of simultaneously entering information on several visual signal signs by frog brain neurons]. AB - Experiments were performed on frogs. It was shown that 9 neuron types with narrow and wide-band sensitive characteristics were present in the tectum. These neurons used different modifications of spatio-temporal codes for transfer information about three features of a moving visual object--its orientation, direction and speed. There are proposed conceptual models of neural networks which perform analysis of the visual object orientation, direction and speed of its movement. These models include conceivable structures composed of narrow- and wide-band neurons which "calculate" the parameters of a visual signal through "synaptic interplay" of excitatory and inhibitory inputs based on their different weights on the "recognitive" ("calculative") neuron membrane. PMID- 8485195 TI - [Display of activities of integrative brain mechanisms in its bioelectrical activity]. AB - Integrative processes taking place in CNS lie in the basis of the activity of the whole brain, i.e. they perform as a system-creating factor; they maintain the system stability, succession of its functioning, regularity of intra-system connections and their reproduction. Can this activity appear in extremely mobile, polyform EEG processes? The results of EEG factor analysis show the existence of the very stable uniform structure of spatial interactions of cortical potentials. This structure can be reproduced from EEG of different adult individuals, as well as of children at various stages of ontogenesis. EEG from any point of the cortex can be represented as a linear combination of only three orthogonal components. These components are the same for all the cortical regions. Especially local, independent fluctuations in EEG constitute less than 10% for adults and not more than 20% for newborns. Apparently, the continuous reflection of oscillations of the whole biopotential field in any point of the cortex reveals in EEG the functioning of a mechanism providing the activity of the brain as a whole. PMID- 8485196 TI - [Modular organization of the cerebral cortex]. AB - Light and electron microscopy original data and other physiological and morphological findings testify that neurons of the cerebral cortex were joined in compact cell ensembles (modules, block). These neuronal modules are self organized in a united morpho-functional system under the repeating impulses which are converged via association callosal and projectional thalamic afferents. A comparative analysis of original and literature data concerning modular organization of the cerebral cortex was performed. A hypothetical model of distinguishing and self assembling of the cortical modules is discussed. PMID- 8485197 TI - [A possible mechanism of action of biogenic amines on the activity of cortical neurons]. AB - Monoaminergic systems are considered as modulating effectiveness of cortical synapses depending on their preceding state and reaction of the whole organism. A differential equation describing activity of cortical cells upon prolonged increased concentration of monoamines in the cerebral cortex is deduced and analysed. A comparison with described experimental data made it possible to consider the serotoninergic system as connected with the positive reinforcement and the noradrenalinergic system--with the negative one. PMID- 8485198 TI - [A unified autocorrelated method of electroencephalogram analysis and some results of its use]. AB - Unified autocorrelation method of EEG analysis (UNIFAC-EEG) represents some optimized algorithms of EEG-signals processing according to the sign of maximum stability to the broadband noise. These algorithms are united by the common aim to identify generation models of these signals narrowband components on the basis of concrete empirical data and estimation of their source dynamic parameters according to the identification results. On the basis of this method it was proved that alpha-rhythm sources belonged to the type of structural stable dynamic systems, and its decrement value could serve as one of the parameters of the functional state of the central nervous system. The effect was found of the interaction between the heart electric fields and human brain in EEG frequent alpha-range. PMID- 8485199 TI - [Non-thermal microwave effect on nerve fiber function]. AB - Effects of microwave radiation (915 MHz, PW, peak SAR 20-30 W/g, pulse duration 1 mcs, 50.000 and 25.000 p.p.s.) were investigated in isolated frog nerve cord preparation. Nerve VHF heating didn't exceed 2.2 degrees C due to intense Ringer's solution perfusion. It was established that nerve irradiation simultaneously with its stimulation lead to significant decrease of action potential amplitude and peak latency. Since the equal conventional heating of the nerve caused the opposite changes (amplitude increase), the results obtained argue for non-thermal mechanism of microwave action. PMID- 8485200 TI - [Visualization of the effects of millimeter radiation on blood plasma]. AB - Experiments on millimeter wave radiation (range 37.5-78.5 Ghz incident radiation power density 1-10 mVt/cm2) upon index refraction of 2-10% water solution of human blood plasma are presented. Investigations were carried out by holographic interferometry with sufficient sensitivity for estimating the index refraction 10(-6). Index refraction variations in 2% water solution of human blood plasma are detected to be equal to 10(-4). Such index refraction variations upon millimeter wave is one order greater than that of the temperature effect and two order greater than the sensitivity of settlement. The mechanism of these phenomena is discussed. PMID- 8485201 TI - The transferrin receptor. AB - Transferrin receptor (TfR) is a membrane receptor involved in the control of iron supply to the cell through the binding of transferrin, the major iron-carrier protein. This receptor plays a key role in the control of cell proliferation because iron is essential for sustaining ribonucleotide reductase activity, and is the only enzyme that catalyzes the conversion of ribonucleotides to deoxyribonucleotides. Furthermore, TfR is overexpressed in several tumors. The synthesis of the receptor is controlled through an iron-dependent negative feedback in cells where the receptor is involved in the control of cell proliferation, but through a positive feedback in cell types involved in iron storage (monocytes-macrophages). Recent studies have shed light on the molecular basis by which iron regulates TfR expression. Thus, the 3' untranslated region of TfR mRNA contains a cis-acting RNA element, termed the iron-regulatory element (IRE), that interacts with an IRE-binding protein (IRE-BP). The high-affinity interaction between IRE-BP and IRE in the TfR mRNA leads to repression of mRNA degradation and thus to higher synthesis of TfR. Hence, the study of IRE-BP activity will elucidate the mechanisms that modulate TfR expression in normal and malignant cells. PMID- 8485202 TI - Neoplastic transformation of human cells in vitro. AB - Efforts to investigate the progression of events that lead normal human cells in culture to become neoplastic in response to carcinogenic agents have been aided by the development of the suitable in vitro model systems. For initial human cell transformation studies, a flat, nontumorigenic clonal line, originally derived from a human osteosarcoma (HOS), was used. When treated with chemical carcinogens such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and 3-methyl-cholanthrene (3MC), the HOS cells underwent morphological alterations and acquired tumorigenic properties. These cell lines were very useful inasmuch as a non-ras cellular transforming gene, met, and an activated H-ras oncogene have been isolated from MNNG-transformed and 3MC-transformed HOS lines, respectively, by DNA transfection procedure. Alteration of p53 gene in chemically transformed HOS cell lines has recently been shown. Although carcinogens cause human cancer, normal human cells in culture have proven difficult to achieve. Neoplastic transformation of human cells in culture has recently been achieved by a stepwise fashion-immortalization and conversion of the immortalized cells to tumorigenic cells. One of the critical initial events in the progression of normal human cells to tumor cells is the escape from cellular senescence. With few exceptions, normal human cells require immortalization to provide a practical system for transformation studies. Thus, the role of carcinogenic agents in the development of human cancers is now being defined using a variety of human cells. The neoplastic transformation in human cell cultures is reviewed. In doing so, this author attempts to put into perspective the history of human cell transformation by carcinogenic agents, and to discuss the current state of the art in transformation of human cells in culture; thus providing insight into the molecular and cellular mechanisms involved in the conversion of normal cells to a neoplastic state of growth. PMID- 8485203 TI - Clinical aspects of acute myeloid leukemias of the FAB types M3 and M4Eo. The AML Cooperative Group. AB - Acute promyelocytic leukemia (AML FAB M3, APL) and acute myelomonocytic leukemia with abnormal eosinophils (AML M4Eo) are considered distinct entities with characteristic clinical, morphological, cytogenetic, and prognostic features. Promyelocytic leukemia is characterized by abnormal promyelocytes replacing normal hematopoiesis associated with a translocation between the long arms of chromosomes 15 and 17 t (15; 17), severe coagulopathy, and responsiveness to all trans retinoic acid (tretinoin). Characteristic features of AML M4Eo are a myelomonocytic marrow infiltration, eosinophils with abnormal immature granules positive for chloroacetate esterase, an inversion or translocation of chromosome 16, and an increased risk of meningeal relapses. Prognosis of both types of AML has been reported to be better than prognosis of the other entities combined. Since most of the published data were collected from heterogeneous patient populations treated with various chemotherapeutic regimens, we have analyzed treatment outcome of AML M3 and M4Eo in the AMLCG-85 study for patients younger than 60 years. For the total population of 594 patients of this study, CR rate was 68.89%, early death rate 11.60%, and no or partial remission was achieved in 19.51% of the cases. Of 40 patients with AML M3 or M3 v complete remission was attained in 62.5%. Nine patients died within 42 days after the start of antileukemic therapy (22.5%). Of these nine, four died because of infection, five because of bleeding. Relapse-free survival rate was 59% after 3 years, significantly better than the respective curve of the other FAB types combined (35% after 3 years). In AML M4Eo, 91.7% of the 24 patients reached complete remission. The early death rate was 8.3%. No case of nonresponse was seen. Relapse-free survival rate was 49% after 3 years compared with 35% for the other types combined. PMID- 8485204 TI - Reproducibility of the morphological diagnostic criteria for acute myeloid leukemia: the GIMEMA group experience. AB - Diagnostic reproducibility of the FAB morphological subtypes of acute leukemia is a basic step in the assessment of the clinical outcome in multicenter trials. Unusual cytologic variables and slightly different interpretations of the FAB morphological criteria have been the most significant factors affecting the overall diagnostic concordance rate among the various centers. An evaluation of the diagnostic concurrence between 35 institutions of the Italian Cooperative Study Group GIMEMA and two reviewers of the ad hoc morphological committee has been performed on 377 patients entering the AML 8A and AML 8B GIMEMA protocols. Overall concordance rate was 62.6%. The most significant differences were observed for M2 vs M4, M4 vs M5, M1 vs M2, and M2 vs M5 subtypes. In order to minimize the impact of some diagnostic deviations on the mean cytologic concordance rate, a distinction between "major" and "minor" discrepancies in the diagnostic procedures has been proposed. When the results of the single institutions were corrected by considering the "major" discrepancies only, a mean diagnostic agreement of 78.1% was reached. PMID- 8485205 TI - Serial changes in endogenous erythropoietin levels in patients with myelodysplastic syndromes and aplastic anemia undergoing erythropoietin treatment. AB - Recombinant human erythropoietin (rhEpo) was administered to 14 patients with myelodysplastic syndrome (MDS) and seven patients with aplastic anemia (AA). In 19 patients, doses of 6000 units were given intravenously three times a week (t.i.w.) with the dose being doubled up to 24,000 units every 8 weeks until a response was obtained. RhEpo was given subcutaneously in two patients. Seven patients, four with MDS and three with AA, showed a significant response with an increase of hemoglobin concentration during therapy. The response occurred at doses of 12,000 units in five and 24,000 units in two patients. Responding patients with both MDS and AA had a relatively low serum Epo (s-Epo) level prior to Epo therapy. MDS responders had either refractory anemia (RA) or RA with ring sideroblasts (RARS), while two of the Epo responders in AA had a severe form of the disease. However, since some of the Epo responders had a high initial s-Epo concentration, a high s-Epo level does not preclude the use of rhEpo. Serial determination of s-Epo levels showed a progressive decline in six of the seven responders even when they were on rhEpo therapy, while the s-Epo levels remained elevated or further increased with time in most nonresponders. RhEpo was well tolerated by all patients. The results suggest that rhEpo is a safe and effective treatment for a certain proportion of patients with MDS and AA. Moreover, serial determination of s-Epo during therapy may be useful in monitoring and predicting the therapeutic effect of rhEpo. PMID- 8485206 TI - Treatment of aplastic anemia with a monoclonal antibody directed against the interleukin-2 receptor. AB - Severe aplastic anemia (SAA) has been related in most cases to underlying autoimmune conditions. Various immunosuppressive regimens have been recommended in the absence of an HLA-identical bone marrow donor. Prednisolone, antithymocyte globulin, and cyclosporin A have been shown to be effective. This report describes the successful treatment of a 23-year-old woman suffering from severe aplastic anemia who had become multiresistant against previously administered immunosuppressive agents, using a monoclonal IL-2-receptor blocking antibody. The patient responded within 4 weeks. The time to the next relapse was 8 months; however, another remission with a second course of horse-antithymocyte globulin was achieved and has been maintained for 27 months to date with low doses of cyclosporin A. Although this is an anecdotical report, IL-2-receptor blockade using a monoclonal antibody might be considered as a further alternative in multi resistant SAA, perhaps increasing the susceptibility to further immunosuppressive trials. PMID- 8485207 TI - Acute sterile inflammation--correlation between cellular changes and extramedullary-produced regulators in vivo. AB - Rats with polyvinylpyrrolidone (PVP)-induced sterile inflammation were used as a model in vivo for investigation of granulopoiesis and extramedullary-produced regulators. The data obtained demonstrated the invasion of massive numbers of granulocytes at the site of inflammation (peritoneal cavity) during the first 24 h of the acute phase of inflammation. To meet the organism's needs for granulocytes the activation of granulopoiesis in bone marrow occurred simultaneously. Accelerated production of granulocytic cells is manifested by involvement of granulocytic proliferative compartment in various stages of differentiation (CFU-GM and morphologically recognizable proliferative granulocytes--PG). Together with cellular changes within the granulocytic cells line, the changes in the content of investigated regulators influencing granulopoiesis were observed. At different time intervals the levels of interleukin-6 (IL-6), colony-stimulating activity (CSA), and granulocytic stimulating activity (GSA) were increased locally at the site of inflammation as well as in serum. The data obtained provide evidence that inducible granulopoiesis during the acute phase of inflammation is under the control of extramedullary-produced regulators, thus confirming their role in the regulation of granulocytic production in vivo. PMID- 8485208 TI - Relation between bone marrow hemosiderin iron, serum iron status markers, and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease. AB - Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18-84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18-90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p = 0.03). Correlations were found between marrow iron and histochemical liver iron (rho = 0.38, p = 0.0001) as well as chemical liver iron (rho = 0.33, p = 0.01). Marrow iron was correlated to S-ferritin (rho = 0.53, p = 0.0001), mean red cell volume (rho = 0.34, p = 0.003), and S-transferrin (rho = 0.24, p = 0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p = 0.001) and controls (p = 0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p = 0.01). Correlations were found between marrow iron and ferritin (rho = 0.64, p = 0.0001), transferrin saturation (rho = 0.56, p = 0.001), transferrin (rho = 0.53, p = 0.001), S-iron (rho = 0.37, p = 0.01), and hemoglobin in women (rho = 0.38, p = 0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron. PMID- 8485209 TI - Treatment of the hematological manifestations of dyskeratosis congenita. AB - Dyskeratosis congenita is a congenital multisystem disorder, characterized by skin pigmentation, dystrophic nails, and leukoplakia. Hematologic abnormalities progressing to severe pancytopenia play a significant role in the poor prognosis of afflicted patients. We report on a patient with dyskeratosis congenita and severe aplastic anemia, complicated by life threatening infection. The patient was treated with recombinant granulocyte-macrophage colony-stimulating factor. This therapy resulted in a moderate and transient improvement in absolute neutrophil counts. Current concepts regarding the pathogenesis and etiology of dyskeratosis congenita are discussed, while reviewing the available therapeutic options. PMID- 8485210 TI - Change of paraprotein from IgG lambda to lambda chain in myeloma. AB - We describe a unique case of IgG lambda myeloma in which a plasma cell leukemia developed and the paraprotein changed from IgG lambda to lambda chain, the latter inducing fatal renal failure. In addition, J-chain was detected in the cytoplasm of the plasma cell leukemia cells. PMID- 8485211 TI - [Structure of lipopolysaccharides from gram-negative bacteria. I. Common characteristics of lipopolysaccharides and lipid A structure (Review)]. AB - The data on the structure and properties of outer membrane lipopolysaccharides of gram-negative bacteria are reviewed with special reference to the general organization of the lipopolysaccharide molecule and the structure of the lipid moiety (lipid A). The correlation between the structure of the lipopolysaccharides and lipid A and their biological properties and functions are discussed. PMID- 8485212 TI - [Structure of lipopolysaccharides from gram-negative bacteria. II. Core structure (Review)]. AB - The review summarizes the data on the core structure of bacterial lipopolysaccharides (LPS) which represents an oligosaccharide binding the lipid moiety of the macromolecule to the O-antigenic polysaccharide chain. Both S strains with complete LPS and R-mutants having various defects of the core biosynthesis are considered. The role of the core in the outer membrane functioning and manifestation of antigenic specificity of LPS is discussed. PMID- 8485213 TI - [Phosphorus-containing polysaccharides from the cell wall of Actinoplanes sp. INA 3697 cell wall]. AB - A phosphorus-containing polysaccharide has been isolated from defatted cells of Actinoplanes sp. INA 3697. The structure of the polymer has been established by a non-destructive method including one- and two-dimensional NMR 1H-spectroscopy as well as by NMR 13C-spectroscopy and confirmed by chemical analysis of the monosaccharide composition and the repeating link. Association of the repeating units-2-acetamido-2-deoxy-beta-D-mannopyranosyl-(1-->3)-2-acetamido -2-deoxy-D glucopyranoses, is provided by phosphodiester bonds between C1 of N acetylglucosamine and C6 of N-acetylmannosamine. The polymer molecule is made up of about 12 disaccharides and is localized in the cell wall of the actinomycete. No structurally identical phosphorylated polysaccharides have as yet been found in prokaryotes. PMID- 8485214 TI - [Features of interaction of Escherichia coli DNA polymerase I and its Klenow fragment with dTTP gamma-p-azidoanilide]. AB - gamma-p-Azidoanilidate of dTTP was used to study the photoaffinity modification of DNA polymerase I and Klenow fragment. The analog was found to be a mixed-type inhibitor with respect to dTTP of the polymerization reaction catalyzed by DNA polymerase I and Klenow fragment. In the absence of the reagent both UV irradiated enzymes were rapidly inactivated. Substrates (dNTP and template primer) protected the enzymes from inactivation by UV-light with different efficiency. In the presence of the template-primer UV-irradiation induced activation of DNA polymerase I. The effect of the analog on both enzyme forms under irradiation is different. At concentration of 10(-5)M gamma-p-anilidate of dTTP accelerated the activation of DNA polymerase I initiated by UV-irradiation and at 10(-4)M concentration it inactivated the enzyme by 20-25%. Under such conditions one enzyme molecule covalently bound two molecules of the analog. While the template-complementary substrate (dTTP) protected DNA polymerase I both from inactivation and modification, the non-complementary one (dCTP) worked only against modification. In contrast to DNA polymerase I Klenow fragment was not inactivated when exposed to UV-irradiation and gamma-p-anilidate of dTTP neither modified the protein nor exerted any significant effect on its polymerization activity. The data accumulated suggest the presence on the DNA polymerase I molecule of a regulatory region providing additional dNTP binding sites. PMID- 8485215 TI - [Creation of Delta mu(H)+ equal to 250 mV on the inner mitochondrial membrane is necessary, but not a sufficient condition for ATP synthesis]. AB - Electron transport in the NADH-ferricyanide and succinate-->O2 chains and ATP synthesis in mitochondria under different incubation conditions have been studied. Ferricyanide which substitutes oxygen as a terminal acceptor provides the generation on the membrane potential, delta microH+, but does not initiate the functioning of the proton cycle. It is suggested that mitochondria can utilize delta microH+ only during the functioning of the redox chain under aerobic conditions. Presumably, under normal conditions oxygen implements two (but not one) functions; the second function of O2 may consist in the formation of a superoxide radical anion. Under conditions of decoupling caused by the free radical scavenger propylgallate, the ATP synthesis in mitochondria may be stimulated de novo through superoxide generation. This effect is abolished by superoxide dismutase. PMID- 8485216 TI - [Effect of 5H-alpha-cholest-8(14)-en-3-beta-ol-15-one on cholesterol metabolism in cultured rabbit hepatocytes]. AB - The effects of 15-ketosterol on cholesterol metabolism in cultured rabbit hepatocytes were characterized by the following parameters: a) cholesterol synthesis, b) apo B and apo E secretion, c) bile acid synthesis. 15-Ketosterol used at therapeutic concentration (0.25 microM) reduced cholesterol synthesis (by 50%). Marked inhibition (by 70%) of apo B and apo E secretion was observed for this agent. Synthesis and secretion of the total [14C]-labeled protein remaining unchanged. 15-Ketosterol did not influence the bile acid synthesis in primary culture of rabbit hepatocytes. These results are suggestive of a new putative mechanism of hyperlipidemic action of 15-ketosterol by a simultaneous decrease of hepatic cholesterol synthesis and secretion of apo B-containing particles. PMID- 8485217 TI - [Certain functional characteristics of enzymatic antioxidant defense in human blood plasma]. AB - It has been shown that human blood plasma displays a low activity of superoxide dismutase, a key enzyme of antioxidative protection. This enzyme was isolated and purified from human blood plasma by using a novel procedure based on gel filtration on Ultrogels AcA-34 and AcA-44. Data from gel filtration and disc electrophoresis in the presence of sodium dodecyl sulfate and beta mercaptoethanol suggest that the molecular mass of the enzyme decreased with time and a simultaneous change in activity. Purification of superoxide dismutase from blood plasma revealed the presence of low molecular mass peptides (1000 and 5000 Da) which inhibited the enzyme activity. A possibility was considered for superoxide dismutase transition into an active, conformationally labile state after a split-off of the inhibiting fragment under conditions of oxidative stress. PMID- 8485218 TI - [Regulation of cholesterol absorption in human and rat small intestine epithelial cells]. AB - Cholesterol absorption in human small intestine organ culture and rat small intestine epithelial cell culture IRD-98 has been studied using [14C] cholesterol, [3H] cholesterol and [14C] sitosterol. It has been found that cholesterol absorption is a dose- and time-dependent process, while sitosterol absorption is not and makes up to about 25% of the total cholesterol absorption. Cholesterol absorption appeared to be a specific process. The endocytosis inhibitor monensin decreased specific cholesterol absorption by 37%. Cholesterol absorption was examined under different conditions influencing cholesterol metabolism in the cell. Loading of IRD-98 cells with non-lipoprotein cholesterol caused a dose-dependent decrease of cholesterol absorption. The inhibitor of acyl coenzyme A:cholesterol acyl transferase (ACAT), compound Sandoz 58-035, had a similar effect on cholesterol absorption. Lovastatin, an inhibitor of 3 hydroxymethyl-3-glutaryl coenzyme A (HMG-CoA) reductase, stimulated cholesterol absorption in a dose-dependent manner. Loading of cells with cholesterol, lovastatin and Sandoz 58-035 had no effect on sitosterol absorption. The possibility has been demonstrated of using human small intestine organ culture and rat small intestine epithelial cell culture IRD-98 as models for studying cholesterol absorption. PMID- 8485219 TI - [Simulating and inhibiting effect of individual blood serum transport proteins on thyroid hormone binding with human placental cell membrane]. AB - Binding processes in in vitro systems modelling specific interactions between transport and receptor proteins, thyroid hormones of human placental tissue and the washing blood, have been studied. These systems included syncytiotrophoblast villous membranes, thyroxine (T4), triiodothyronine (T3) and iodothyronine binding proteins: transthyretin, albumin, immunoglobulins (Ig) M and G, apolipoprotein A-I, and the T4-binding globulin purified from human retroplacental serum. All of the transport proteins at concentrations close to the Ka values of their complexes with thyroid hormones produced inhibitory effects on the binding of [125I]T3 or [125I]T4 to the thyroid hormone membrane receptor. The dependence of [125I]T4 membrane binding on IgM concentration in the system was characteristic of all proteins studied. In the case of T3 such dependence was unique for IgM, and included the phase of the IgM stimulatory effect (10(-11)-10(-9) M) and the phase of inhibition (10(-8)-10(-7) M). In the presence of 30 pM IgM, the concentration of the membrane T3-binding sites increased by 75% with a 2.2-fold decrease of the association constant (Ka). It was shown that IgM interacts specifically with two classes of binding sites on the plasma membranes with Ka(1) = 5.0 x 10(9) M-1, Bmax(1) = 34 fmol/mg of membrane protein and Ka(2) = 2.7 x 10(7) M-1, Bmax(2) = 2.0 pmol/mg of membrane protein. It is suggested that the stimulatory effect of IgM is caused by increases in the number of T3-binding sites on the placental villous membranes as a result of complex formation between IgM and its membrane receptor which displays an enhanced T3-binding activity. PMID- 8485220 TI - [Metabolism of nuclear neutral lipids and rat thymocyte chromatin under normal conditions and after gamma-irradiation]. AB - The levels and specific radioactivities of cholesterol and free fatty acids in nuclei and chromatin of thymocytes from normal and gamma-irradiated (10 Gy) rats have been studied. The radioactivity of the total lipid fraction of gamma irradiated cells was decreased significantly in the absence of inhibition of [2 14C]acetate incorporation into the total protein and lipid reactions and the [3H]uracil incorporation into the acid-insoluble RNA. The concentration of free fatty acids in the nuclei increased significantly after irradiation. The specific radioactivity of cholesterol in chromatin was higher than in the nuclei. The differences in specific radioactivities of free fatty acids were less pronounced. After irradiation the ratio of specific radioactivities of free fatty acids in chromatin to that in the nuclei showed a tendency to increase. PMID- 8485221 TI - [Isolation and characteristics of catalytic antibodies to DNA in systemic lupus erythematosis]. AB - A method for purifying DNA-specific catalytic antibodies based on affinity chromatography on protein A Sepharose and on both modified and non-modified DNA cellulose as well as HPLC has been developed. The elution conditions with high yields of DNA-hydrolyzing activity of antibodies have been optimized. The biochemical and immunological properties of catalytic antibodies have been examined. The kinetic parameters of the enzyme interaction with an oligonucleotide substrate have been determined. The influence of effectors on DNA hydrolysis by antibodies has been investigated. PMID- 8485222 TI - [Characteristics of phospholipid hydrolysis kinetics by phospholipase C from Bacillus cereus. Hydrolysis of phosphatidylinositol in various aggregated states]. AB - The process of phospholipase C hydrolysis of phosphatidylethanolamine (PE) in the form of mixed micelles phospholipid-detergent or in the form of vesicules in the mixture with phosphatidylcholine (PC) was studied. The size of the micelles was measured by dynamic light-scattering and their structure was determined by 31P NMR spectroscopy. It was found that the kinetics of PE hydrolysis in the micelles by phospholipase C from Bacillus cereus do not follow Michaelis-Menten equation, but at all concentrations studied PE was hydrolyzed significantly slower than PC. The rate of PC hydrolysis was measured in the previous work. The hydrolysis of PE in PC-vesicules was followed with use of Victoria blue R dye method. It was shown that the rate of PE hydrolysis in the vesicules is similar to that of PC. PMID- 8485223 TI - [Modification of RNA ligase histidine residues by diethylpyrocarbonate]. AB - The practicality of Tris-HCl buffer for modification of histidine residues by diethylpyrocarbonate (DEPC) was studied using a model protein-hexokinase. It was found that modification was selective at pH 7.5. Conditions for modification of one histidine residue in the protein molecule were specified. In 30 mM Tris-HCl buffer pH 7.5, 10-min interaction of RNA-ligase with 0.3 mM DEPC was accompanied by modification of one histidine residue, as a result of which the ability to form a covalent AMP-RNA-ligase complex decreased 3 times. Modification of two histidine residues of RNA-ligase resulted in a complete loss of the enzyme activity. At increasing DEPC concentration modification affected all of the seven histidine residues of RNA-ligase. The kinetic parameters (Km and V) for the native and modified enzymes were determined and compared. PMID- 8485224 TI - [Comparative characteristics of some parameters of the cell nucleus in the series myeloma-hybridoma-lymphocyte]. AB - A comparative study of several parameters of the cell nuclei of hybridoma MLC-1c and its parent cells--myeloma X-63.Ag8.653 and spleen lymphocytes of Balb/c mice, has been carried out. The results of cytogenetic studies suggest that although the hybridoma and myeloma cell lines used in this study are rather stable, they contain some proportion of the altered chromosomal material. Two-dimensional electrophoresis performed according to O'Farrell revealed that the similarity between the relative presentation and reciprocal location of the nuclear proteins expressed by the myeloma and the hybridoma was greater than that between these cell lines and lymphocytes. Probing of the chromatin structure by micrococcal nuclease showed no significant differences in the degree of nuclease resistance of chromatin between myeloma, hybridoma and lymphoid cells. A comparative study of the Ca/Mg-dependent endonuclease activity of the nuclei in situ and in nuclear extracts demonstrated that whereas its content in lymphocytes was rather high, in myeloma and hybridoma it was practically absent. At the same time, cell nucleus extracts of the myeloma and the hybridoma contained high amounts of DNA-binding proteins which were undetectable in mouse spleen lymphocytes. PMID- 8485225 TI - [Change in adenine nucleotide pool in E. coli 1257 bacterial cells under the action of a low intensity He-Ne laser]. AB - Evidence is presented of co-immobilized bioluminescent reagents which include firefly luciferase, pyruvate kinase and adenylate kinase used for an adenylate assay in bacterial cells. The changes in the ATP, ADP and AMP content induced by irradiation with a low-power He-Ne-laser depend on the laser power and irradiation dose. The data obtained suggest that laser irradiation causes the activation of adenine nucleotide synthesis de novo. PMID- 8485226 TI - [The effect of monovalent cations on the structure of chromatin from Ehrlich ascites carcinoma cells]. AB - Changes in the intracellular ratio of monovalent cations resulting in the alteration of transcriptional activity in some cell-specific genes have been investigated. It was found that at varying intracellular Na+/K+ concentration ratios the accessibility of the beta-actin gene to the effect of exogenous DNAaseI changes drastically. The use of hybridization of restricted DNA of the nuclear matrix with appropriate probes revealed that the number of copies for oncogenes c-fos and c-myc within this DNA changes with alteration of the intracellular ratio of monovalent cation concentrations. PMID- 8485227 TI - [Nuclear proteins, specifically binding the regulatory region of rat tryptophan oxygenase]. AB - Using electrophoretic mobility shift assay we have analysed the binding of rat liver nuclear proteins to the fragments from -466 to -292 and from -292 to -178 relative to the transcriptional start site of the rat tryptophan oxygenase gene. Studies of the competition with a synthetic consensus sequence for the NF 1 recognition site have shown that the liver nuclear proteins, responsible for the formation of specific complexes with these fragments belong to the family of the nuclear factor 1 (NF 1). We have also found that the trans-acting factors of the NF 1 family form several complexes with each of the two tested fragments of the tryptophan oxygenase gene. PMID- 8485228 TI - [Probucol and alpha-tocopherol stimulate the synthesis of bile acids in cultured rabbit hepatocytes]. AB - Primary cultures of rabbit hepatocytes were used to examine the effect of probucol and alpha-tocopherol on cholesterol and bile acid metabolism. After 24 hour preincubation of cells with 100 microM probucol, the cholesterol and cholesteryl ester content increased--by 30% and 50%, respectively. This was accompanied by decreasing incorporation of [14C]acetate into cholesterol (down to 25-35%). At the same time, alpha-tocopherol had no effect on cholesterol accumulation in hepatocytes, while cholesterol synthesis was stimulated by 30 50%. Addition of 100 microM probucol or alpha-tocopherol to a culture medium containing 10% fetal calf serum and [14C]cholesterol caused a significant (30 40%) stimulation of bile acid synthesis. Stimulation by probucol was dependent on the presence of exogenous plasma or HDL2 cholesterol, while alpha-tocopherol enhanced this process in a cholesterol-free medium. Stimulation (40%) of bile acid secretion by probucol in the presence of physiological concentrations of apo E-free HDL2 was found. Study of receptor-mediated uptake of HDL2 revealed that: (i) probucol stimulated apo E secretion; (ii) HDL2 isolated from a medium of probucol-treated cells contained 2-3 times more apo E than the particles preincubated with cells without the drug; (iii) apo E-enriched HDL2 particles were incorporated into cultured human skin fibroblasts 1.5-3.0 times more effectively than apo E depleted HDL2; (iv) monoclonal antibody against the LDL receptor binding domain of apo E effectively (by 40%) inhibited the apo E enriched HDL2 uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485229 TI - [Properties of beta-carotene-15,15'-dioxygenase, stabilized during purification with lutein and dithiothreitol]. AB - Preparations of beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) obtained with or without lutein and dithiothreitol (DTT) as stabilizers display similar properties. The stabilized preparation has an apparent Km of 17 microM and Vmax of 2.8 nM/h/mg of protein, a pH optimum of 8.1, is sensitive to SH-agents and is activated by Fe2+, DTT or glutathione used at optimal concentrations of 0.5 mM, 2 mM, and 5 mM respectively. At DTT concentration above 2 mM the enzyme activity decreases drastically, which testifies to the importance of maintaining the thiol and disulphide group ratio in the protein molecule at an optimal level. At 4 mM Fe2+ there occurs a nonenzymatic formation of apo-carotenals; however, retinal is formed only after addition of commensurate amounts of thiol compounds. The enzyme activity depends on the ionic strength of the incubation medium, the maximal effect being observed with 0.4 M K-phosphate buffer. Substitution of phosphate for Cl- partly inhibits the enzyme. The optimal temperature for this reaction is 45 degrees. A simultaneous use of optimal incubation parameters (2 mM DTT, 0.4 M K-phosphate buffer pH 8.1 and 45 degrees C) increases the retinal yield 2.5-fold against control. PMID- 8485230 TI - [Signal-conducting and low molecular weight GTP-binding proteins from the lung and endothelium: localization in membranes and cytosol, interaction with F actin]. AB - The following proteins have been identified in mammalian lung and endothelium, using [32P]ADP-ribosylation by bacterial ADP-ribosyltransferase, immuno- and [alpha-32P]GTP-blottings: 41 kDa Gi1 alpha, 40 kDa Gi2 alpha, 41 kDa Gi3 alpha, 40 kDa and 45 kDa subunits of GS alpha, 36 kDa beta 1 and 35 kDa beta 2 subunits of signal-transmitting GTP-binding proteins (G-proteins), the 19-26 kDa low molecular weight GTP-binding proteins (SMG-proteins) ras, rho, rac, G25K (Gp), as well as ARF and SMG proteins binding with a high affinity to [alpha-32P]GTP. These G- and SMG-proteins are contained in various proportions in membrane and cytosol fractions of lung and endothelium cells. Subunits Gi2 alpha and GS alpha (but not beta 1 or SMG-proteins) my partially (approximately 1%) dissociate from the membrane by the action of the GTP analogs GTP[S] or Gpp(NH)p in the presence of magnesium ions. Extraction with low ionic strength buffer solutions in the presence of EDTA is accompanied by the release of G-actin sensitive to whooping cough toxin Gi2 alpha and beta i subunits. The functionally coupled into a alpha beta gamma heterodimer Gi-protein subunits (predominantly Gi2 alpha and beta i) present in the cytosol fraction as well as the SMG-proteins revealed by [alpha 32P]GTP-blotting (but not the SMG-proteins sensitive to the botulinic C3 exoenzyme, rho/rac, or ARF, may interact with F-actin. Approximately 20% of these proteins are associated with the Triton X-100 insoluble (cytoskeletal) fraction of the endothelium. A conclusion is drawn that interactions of G- and SMG proteins with actin filaments may be the reason for the formation of "multidisperse" structure in a cell. PMID- 8485231 TI - [The role of GTP-binding proteins in regulating the activation of Na+/H+-exchange and Na+, K+, 2Cl- cotransport: effect of fluoride ion]. AB - The effects of NaF and AlCl3 on basal and stimulated by hyperosmotic shock activities of Na+/H(+)-exchange and Na+, K+, 2Cl(-)-cotransport in rat smooth muscle and red blood cells have been studied. Preincubation of cells with 10 mM NaF leads to inhibition of basal and hyperosmotic shock-activated Na+, K+, 2Cl(-) cotransport in smooth muscle cells--by 45% and 190%, respectively. Sodium fluoride causes 80% activation of basal Na+, K+, 2Cl(-)-cotransport in red blood cells with no effect on the transport induced by hyperosmotic shock. The effect of NaF on Na+, K+, 2Cl(-)-cotransport in red blood cells does not depend on Al3+. Basal Na+/H(+)-exchange is stimulated by NaF by 780% in smooth muscle cells and is insensitive to the fluoride in red blood cells. Under hyperosmotic conditions NaF activates Na+/H(+)-exchange by 100% in smooth muscle cells and by 130% in red blood cells; in the latter case its effect is potentiated by Al3+. The data obtained suggest that GTP-binding proteins are involved in the activation of Na+/H(+)-exchange under hyperosmotic conditions. PMID- 8485232 TI - [Effect of training on the structural-metabolic indicators in athletes' skeletal muscles]. AB - Muscle biopsy samples were taken from m.vastus lateralis of ski-runners during the training season and 4 months after training (consisting presumably of aerobic exercises). Metabolic enzyme activities, fiber cross-sectional areas, capillary supply indices and parameters of oxygen uptake by intact mitochondria in skinned fibers were measured. Training did not induce any appreciable changes in the NADH tetrazolium reductase activity, maximal oxygen uptake by mitochondria, mean fiber size or capillary density. At the same time, there were significant increases in the cytochrome c oxidase activity, respiratory control index and creatine stimulated respiratory rate. The activities of alpha-glycerophosphate dehydrogenase, malate dehydrogenase and myoglobin peroxidase as well as the basal respiratory rate of mitochondria decreased as a result of training. The data obtained testify to the possibility of qualitative adaptations in the respiratory chain of mitochondria. PMID- 8485233 TI - [Binding of phenyldicarbaundecaborane with proteins, membrane fragments, and whole cells]. AB - The binding of the lipophilic synthetic anion, phenyldicarbaundecaboran, to inner and outer membranes of myocytes, platelets and erythrocytes as well as to integral and surface membrane proteins has been studied. It has been found that the distribution of lipophilic synthetic ions in the system biopreparations- aqueous phase is not determined by the value of the transmembrane difference of electric potentials but, rather, by ion adsorption by the protein-lipid components of the cell. The latter is controlled by the correlation between the volume of hydrophobic areas and the local electrochemical characteristics of the cell. PMID- 8485234 TI - Tumor necrosis factor-alpha gene expression in mouse oocytes and follicular cells. AB - Ovarian cells that transcribe and translate the gene for tumor necrosis factor alpha (TNF alpha) were identified in the adult cyclic mouse by using in situ hybridization and immunocytochemistry. TNF alpha mRNA was observed in > 97% and protein was contained in approximately 53% of the oocytes of healthy follicles with two or more layers of granulosa cells, but neither was detectable in oocytes of primordial follicles and follicles with a single layer of granulosa cells. In early atretic follicles, only 13% contained TNF alpha protein and 40% contained TNF alpha mRNA. In late stages of atresia, intense immunoreactive TNF alpha was observed in all of the oocytes, but TNF alpha mRNA was present in only 13%. In approximately 85% of follicles, theca and/or granulosa cells exhibited TNF alpha mRNA hybridization signals. Macrophage-like cells within the interstitium were positive for TNF alpha mRNA and protein. In corpora lutea, luteal cells and macrophage-like cells contained TNF alpha message, while only the latter lineage contained immunoreactive TNF alpha. Hybridization signals and immunoreactivity were more intense in older corpora lutea than in corpora lutea of the present cycle. Northern blot analysis revealed a 2.2-kb TNF alpha mRNA in the ovary that was unchanged relative to 28S rRNA (constitutive RNA) during the cycle. Similarly, TNF alpha hybridization signals and immunoreactivity did not appear to change throughout the cycle. These results indicate that TNF alpha gene transcription in the oocyte coincides with the synthesis of immunoreactive TNF alpha and that these complex biochemical processes occur at distinct steps of follicular development in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485235 TI - Multiple generational bovine embryo cloning. AB - Repeated cycles (multiple generations) of nuclear transfer procedures have the potential of producing a large number of identical offspring from the micromanipulation of one mammalian embryo. This paper outlines the differences in nuclear transfer procedure efficiencies and developmental rates for the various stages and generations of embryos. We report the production of 54 genetically identical embryos that developed to the morula stage from one parent embryo. When a limited number of nuclear transfer embryos (clones) were transferred to recipient females, first, second, and third generation calves were born. Clones cultured for 5 days in the sheep oviduct had a greater number of cells (28.1 +/- 1.7) than clones cultured for 4 days (17.8 +/- 1.7). However, fusion rates were lower for Day 5 clones (Day 5, 57% vs. Day 4, 68%; p < 0.001) used as donors for the next generation of cloning. Different generations of clones also varied in fusion rates. Fusion rates generally declined with each additional generation and ranged from 66% for the parent-donor embryos to 52% for second generation donors (p < 0.01). Developmental rates were highest for first and third generation donors (20% and 19%) and lowest for second generation donors (10%; p < 0.001). Further understanding of the factors that are conducive to high developmental rates and nuclear reprogramming may make it possible to produce an unlimited number of genetically identical animals. PMID- 8485236 TI - Involvement of cyclins and cdc2 serine/threonine protein kinase in human sperm cell function. AB - The presence and roles of mitotic cyclins (cyclin A and cyclin B1), and cdc2 and related (having an N-terminal PSTAIRE conserved sequence) serine/threonine protein kinases were investigated by use of specific antibodies. The cyclin A and cyclin B1 antibodies reacted specifically with the acrosomal regions of human sperm cells in the indirect immunofluorescence technique (IFT) and recognized the specific band of p60 (cyclin A) and p62 (cyclin B1) on the Western blot of sodium deoxycholate (DOC)-solubilized noncapacitated human sperm preparation. Both antibodies reacted more strongly with the specific cell region/band of capacitated sperm than with that of noncapacitated sperm. The cdc2 and PSTAIRE antibodies also reacted predominantly with the acrosomal regions of human sperm cells in IFT and recognized the specific band of 34 kDa corresponding to p34 cdc2 protein on the Western blot of DOC-solubilized noncapacitated human sperm preparation. Again, both antibodies reacted more strongly with the specific cell region/band of capacitated sperm than with that of noncapacitated sperm. The cyclin A antibodies (but not the cyclin B1 antibodies) and cdc2 antibodies as well as the PSTAIRE antibodies significantly (p = 0.02 to p < 0.001) increased (rather than decreased) the human sperm penetration rates of zona-free hamster ova; the cyclin A and cdc2 antibodies showed the strongest enhancing effects. These three antibodies significantly increased the acrosome reaction and release of acrosin activity from the sperm cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485237 TI - Neonatal porcine endometrial development involves coordinated changes in DNA synthesis, glycosaminoglycan distribution, and 3H-glucosamine labeling. AB - To determine whether neonatal porcine endometrial development involved alterations in endometrial DNA synthesis, glycosaminoglycan (GAG) distribution, and/or 3H-glucosamine labeling, gilts were assigned randomly at birth (Day 0) to be hysterectomized on either Day 0, 7, 14, 28, 42, or 56. Uteri were processed for histology and Alcian blue-8GX (AB) histochemistry or cultured as explants in the presence of [methyl-3H]thymidine (3H-Thd) or D-[6-3H]glucosamine (3H-GlcN) and processed for subsequent autoradiography. For 3H-Thd-labeled tissues, labeling index (LI; % of nuclei labeled) was determined for two endometrial tissues (epithelium and stroma); two epithelial areas (luminal and glandular); and, for glandular epithelium, in three endometrial zones (zone 1 = shallow, zone 2 = intermediate, zone 3 = deep). For 3H-GlcN-labeled tissues, LI (grains/100 microns2) was determined for two stromal zones (shallow and deep). Endometrial glands were absent on Day 0, present in shallow stroma on Days 7 and 14, and extended to the myometrium in tissues from Day 28 through Day 56. Appearance of endometrial glands was associated with a dramatic increase in glandular epithelial 3H-Thd LI, which was maximal on Days 7 and 14 and declined thereafter. When glands were present in all three endometrial zones (Days 28-56), glandular epithelial 3H-Thd LI was consistently greatest in zone 2. Stromal 3H-Thd LI decreased after Day 0. In tissues obtained after Day 0, a distinct zone of alcianophilia was observed in shallow stroma adjacent to luminal epithelium and surrounding the necks of newly developed endometrial glands. This staining pattern was marked in tissues from Days 7, 14, and 28. Generally, stromal 3H-GlcN LI was greater in shallow than in deep stromal zones; it decreased after Day 0 to minimum values on Days 28 and 42 in both zones, and increased slightly in shallow stroma on Day 56. Data indicate that development of the neonatal porcine endometrium between birth and Day 56 involves coordinated alterations in patterns of DNA synthesis, GAG distribution, and glycoconjugate biosynthesis. The morphogenetic processes characterized here are likely to be regulated locally via changes in tissue microenvironment. PMID- 8485238 TI - Neonatal age and period of estrogen exposure affect porcine uterine growth, morphogenesis, and protein synthesis. AB - To determine whether neonatal age and estrogen exposure affect uterine growth, morphogenesis, and protein synthesis, crossbred gilts were randomly assigned at birth (Day 0) to receive either corn oil vehicle (CO) or estradiol-17 beta valerate (EV; 50 micrograms/kg BW/day). Gilts were treated for 7 days, chosen to coincide with specific periods of uterine development, prior to hysterectomy on Day 7, 14, or 49. Uteri were weighed, and tissues were fixed for histology or explanted with L-4,5-[3H]leucine (3H-leu) for 24 h. Endometrial and myometrial thicknesses were measured in uterine wall cross sections. Radiolabeled proteins produced by uterine wall tissues from 3H-leu and released into explant medium were identified by fluorography of two-dimensional SDS-PAGE gels. Proteins for which fluorographic spot intensities were consistently affected by age and/or treatment were excised from gels, and associated radioactivity was quantified. Normal growth and histogenesis were observed in uteri from CO-treated gilts. Exposure to EV increased (p < 0.01) uterine wet weight on all days examined, although effects were most pronounced on Day 49 (day x treatment, p < 0.01). Histologically, uteri of EV-treated gilts exhibited precocious or altered patterns of development of endometrial glands and folds. Endometrial thickness was greater (p < 0.01) in EV-treated gilts, and response was most pronounced on Day 49 (day x treatment, p < 0.01). Treatment with EV increased (p < 0.01) myometrial thickness on Day 49 only. Twenty-five uterine proteins were identified to be affected consistently by neonatal age, EV, or both. Production of four of these proteins was affected by age alone, while six were affected exclusively by treatment with EV alone, and 15 were affected differentially by both age and EV. Treatment with EV affected production of three of these 25 proteins on Day 7, 8 of 25 on Day 14, and 14 of 25 on Day 49. Results indicate that uterine growth and development of the porcine uterine wall during early neonatal life are accompanied by predictable alterations in patterns of uterine protein synthesis. Data also demonstrate that the neonatal porcine uterus is estrogen-sensitive and that both physical and biochemical responses of uterine tissues to estrogen vary with period of exposure. It is suggested that EV may be useful as a tool with which to induce developmental lesions in neonatal porcine uterine tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8485239 TI - Short-day effects of melatonin on luteinizing hormone secretion in the ewe: evidence for central sites of action in the mediobasal hypothalamus. AB - Experiments were designed to localize the central sites of action of melatonin involved in the control of seasonal reproduction. Ewes were exposed to long days and received microimplants of melatonin in the preoptic area (n = 9), anterior hypothalamus (n = 4), dorsolateral hypothalamus (n = 4), or mediobasal hypothalamus (n = 12). The effects of implants were determined by comparison with control ewes (untreated or sham-operated, n = 10) and with ewes treated with an s.c. implant of melatonin (n = 8) or ewes subjected to short days (n = 8). All ewes were ovariectomized and treated s.c. with a silastic capsule of estradiol. Melatonin released in the preoptic area as well as in the anterior and lateral hypothalamus did not cause any difference as compared with the controls (no stimulation of LH secretion and no inhibition of prolactin secretion). In contrast, melatonin implanted in the mediobasal hypothalamus caused an increase in LH secretion in 7 of the 12 ewes on Day 53.0 +/- 4.2 after implantation (mean +/- SEM). Their response was not different compared with that of ewes treated s.c. with melatonin or exposed to short days either in terms of timing (Day 56.3 +/- 6.2 and 59.5 +/- 3.1, respectively, for controls) or of amplitude of the LH response. Similarly, melatonin caused only a reduction of prolactin secretion in the mediobasal, s.c., and short-day groups. It is concluded that the mediobasal hypothalamus or the surrounding tissues could be the sites of action of melatonin involved in the control of seasonal reproduction. PMID- 8485240 TI - Spermatogonial cell proliferation in organ culture of immature rat testis. AB - Regulatory mechanisms of male germ cell proliferation in mammals were investigated by using in vitro organ culture of immature rat testis. Nutritional and hormonal requirements for maintenance and differentiation of germ cells in vitro were first characterized by testing different culture conditions. FSH was essential for the progression of type A spermatogonia up to the stage of pachytene spermatocytes after 3 wk of in vitro culture, while vitamins A, C, and E, LH, and testosterone were not effective. The proliferative activity of Sertoli cells markedly declined after 1 wk of in vitro culture, irrespectively of the presence of FSH in the medium. In addition, basal testosterone production by Leydig cells was maintained after 1 wk of culture, provided that FSH was present in the medium. The appearance of differentiating type I and type B spermatogonia and meiotic cells in the seminiferous cords throughout culture was accompanied by a significant reduction in the number of undifferentiated spermatogonia. Moreover, a similar labeling index of undifferentiated spermatogonia was observed in both unstimulated and FSH-stimulated testis fragments at all culture times considered. Therefore, FSH did not influence the mitotic activity of undifferentiated spermatogonia, suggesting a differential role of this gonadotropin during the mitotic phase of spermatogenesis. These results indicate that the organ culture system of immature rat testis represents a useful experimental model for studying regulatory mechanisms of spermatogonial cell proliferation. PMID- 8485241 TI - Differential expression of distinct mRNAs for ovine trophoblast protein-1 and related sheep type I interferons. AB - An antiluteolytic substance secreted by the ovine conceptus and primarily responsible for maternal recognition of pregnancy is ovine trophoblast protein-1 (oTP-1), a new type I interferon (IFN). The objectives of this research were 1) to investigate whether multiple, distinct genes encode oTP-1 and other type I IFNs in the ovine genome and 2) to examine expression of oTP-1 and other IFN mRNAs during conceptus development. Genes for type I IFNs were isolated from a subgenomic library constructed from Day 25 (Day 0 = estrus) ovine conceptus high molecular-weight DNA. Six clones were isolated and nucleotide-sequenced from 1000 to +900 (bases relative to cap site). Comparisons of inferred amino acid sequences demonstrated that four clones were distinct oTP-1 genes and that two clones, defined as o9 and o12, were related type 1 IFNs (deduced aa homology of o9 and o12 to oTP-1 was 71% and 54%, respectively). The presence of mRNAs encoded by oTP-1 and type I IFN genes was examined quantitatively via reverse transcription-polymerase chain reaction (RT-PCR) analysis of total cellular RNA (tcRNA) extracted from Day 13-45 concepti. Total cellular RNA obtained from Day 75 placenta and adult lymphocytes was also analyzed by RT-PCR, coupled with Southern blot hybridization of the PCR reaction products with specific DNA probes. PCR products were sequenced in order to confirm primer specificity, and mRNAs corresponding to two of the four oTP-1 genes and to both related IFN clones (o9 and o12) were identified. Furthermore, quantitation of the PCR products revealed that of the two oTP-1 genes examined, one was highly expressed on Days 13-20 and transcripts were weakly detectable on Days 30 and 45. In contrast, the other oTP-1 gene examined was weakly expressed on Days 13-20 only. Densitometric analysis of hybridization signals revealed that IFN o9 mRNA was detected in Day 75 placenta but only weakly detected in conceptus (Days 13-45) and adult lymphocytes. IFN o12 mRNA was abundant in lymphocytes relative to the other tissues examined. Collectively, these results demonstrate the existence of distinct oTP-1 and related type I IFN genes. The data suggest that these genes display differential, tissue-specific expression and developmental regulation during pregnancy. PMID- 8485242 TI - Comparison of the myometrial response to oxytocin during daylight with the response obtained during the early hours of darkness in the fetectomized rhesus monkey at 160-172 days gestational age. AB - Six rhesus monkeys, fetectomized at 122-129 days gestational age (dGA), were studied to evaluate photoperiod-dependent differences in the myometrial sensitivity to exogenous oxytocin in the absence of a live fetus. One to two weeks before the study, at 150-162 dGA, sixteen maternal arterial samples were taken every 4 h to assess plasma concentrations as well as the presence of 24-h rhythmicity in plasma estradiol and cortisol. At 160-172 dGA, oxytocin was administered via the maternal inferior vena cava to elicit regular myometrial contractions. Each animal was studied twice: once during daylight and once during the early hours of darkness. Oxytocin was infused in a pulsatile fashion during the first minute out of every five over four consecutive 30-min intervals, during which the dose rate was increased after each 6-h oxytocin pulse (400, 800, 2000, and 4000 pg.kg-1.min-1). The overall response of the myometrium of the fetectomized animals, evaluated as the number of contractions per pulse of oxytocin, was higher during the daytime study (p = 0.006). The response to oxytocin in intact pregnant animals is greatest during the early hours of darkness. Comparison of the overall myometrial response of the fetectomized monkeys with the response of intact pregnant animals showed that the daytime responses were similar, but that the nighttime response of the fetectomized animals was significantly lower (p < 0.0002). These contrasting findings may be due to differences in the maternal neuroendocrine environment depending on the presence or absence of a fetal adrenal steroid contribution acting directly on the myometrium or acting indirectly through provision of precursors for estrogen formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485243 TI - Local regulation of testicular immunoreactive-arginine vasopressin and steroidogenesis by naloxone. AB - The effects of intratesticular injection of naloxone, a universal opioid antagonist, on testicular immunoreactive (IR)-arginine vasopressin (AVP) content and on in vitro testosterone production by Leydig cells were investigated in the mouse. Bilateral intratesticular injection of increasing doses of naloxone (0.1 10 micrograms/testis) resulted 24 h later in a dose-dependent increase in testosterone production by Leydig cells incubated for 3 h in the presence or absence of hCG (100 ng/ml). Unilateral intratesticular injection of naloxone (10 micrograms) similarly enhanced basal and hCG-stimulated testosterone production by Leydig cells, but production was not modified in Leydig cells from the contralateral vehicle-injected testis, nor was it changed when the same dose was injected subcutaneously. Unilateral intratesticular injection of 10 micrograms naloxone led to a dose-dependent increase in the hCG-responsiveness without altering the slope of the hCG dose-response curve. In vitro exposure of Leydig cells to increasing doses of naloxone (10(-9) to 10(-7) M) did not alter either basal or hCG-stimulated testosterone production. Testicular IR-AVP content declined in a dose-dependent manner in naloxone-injected testis, but remained unchanged in the contralateral vehicle-injected testis and in testis from animals that received similar doses of naloxone subcutaneously. Since AVP has been shown to locally exert a negative control on testosterone production within the testis, it might be hypothesized that the increased Leydig cell activity after local naloxone administration results from reduced intratesticular IR-AVP levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485244 TI - Pattern of lactate production and steroidogenesis during growth and maturation of mouse ovarian follicles in vitro. AB - A model culture system for the study of follicular metabolism has been developed from existing methods of whole-follicle culture. The modified system mimics the in vivo growth and maturation of mouse ovarian follicles from primary to preovulatory stages and the modulating influences of the LH and FSH. This is the first study to demonstrate ovulation in vitro from individual ovarian follicles. The pattern of follicular lactate production relative to steroidogenesis was studied throughout in vitro follicular development over a period of 6 days. Twenty-four-hour samples of medium from individual follicles were analyzed for lactate and pyruvate by an automated analytical technique, and for estradiol and progesterone by an immunoenzymatic method. Follicles produced remarkably large quantities of lactate and estradiol during FSH-stimulated development in vitro. LH further stimulated lactate production but resulted in a significant decrease in estradiol secretion and an ovulation rate of 30%. Progesterone production was not detectable throughout the culture period, and follicles showed no evidence of pyruvate uptake. These findings demonstrate the validity of using this model culture system for the study of follicular metabolism and provide new information on the pattern of carbohydrate metabolism relative to steroidogenesis during follicular growth and maturation. PMID- 8485245 TI - Comparison of luteinized unruptured follicles and corpora lutea: steroid hormone production and response to luteolytic and luteotropic agents. AB - Administration of hCG prior to spontaneous ovulation induces the formation of luteinized unruptured follicles (LUFs) in guinea pigs. Serum progesterone (P) in animals with LUFs is significantly lower. This study was designed to determine whether follicular maturity affected the incidence of LUFs and P production as well as to compare isolated LUFs with corpora lutea (CL) in relation to hormone production and response to luteotropic and luteolytic agents. Ovarian histology and serum steroids following injection of hCG at various times during the estrous cycle indicated that greater follicular maturity increased the incidence of ovulation and P production. LUFs and CL contained equivalent amounts of P/mg tissue, but LUFs were significantly smaller than CL. Cells from CL and LUFs responded to hCG in vitro with significant increases in P release, but the response was greatest with LUFs. Prostaglandin F2 alpha (PGF) attenuated the response to hCG in vitro by mid-cycle CL and LUFs, but not by CL obtained during the early luteal phase. We conclude that the attenuated luteal-phase P profile following induction of LUFs is not an intrinsic deficiency in hormone production, but may arise from the smaller mass of luteal tissue and from earlier than normal development of responsiveness to the luteolytic effects of PGF. PMID- 8485246 TI - Increased glutamine metabolism in bovine cumulus cell-enclosed and denuded oocytes after in vitro maturation with luteinizing hormone. AB - The effects of LH on tricarboxylic acid (TCA) cycle activity within denuded and cumulus cell-enclosed bovine oocytes were investigated by measuring the metabolism of L-[14C(U)]glutamine and [2-14C]pyruvate to 14CO2 after in vitro maturation (IVM) with LH in serum-free, defined culture conditions. Initially, intact cumulus cell-enclosed oocytes or oocytectomized cumulus cell complexes were incubated for 24 h for IVM in control medium alone or supplemented with LH (10 micrograms/ml) before assessment of glutamine metabolism. Glutamine oxidation was increased (p < 0.01) only after IVM of intact cumulus cell-enclosed oocytes with LH when compared to either intact untreated controls, untreated oocytectomized controls, or oocytectomized cumulus cell complexes after LH treatment (0.23 +/- 0.02 vs. 0.13 +/- 0.01, 0.12 +/- 0.01, and 0.12 +/- 0.01 nmol 14CO2/micrograms protein/3 h, respectively). Glutamine metabolism was greater (p < 0.001) in denuded oocytes from cumulus cell complexes that were exposed to LH during IVM versus nontreated controls (6.4 +/- 0.3 vs. 5.1 +/- 0.2 pmol 14CO2/oocyte/3 h, respectively). Glutamine metabolism was increased (p < 0.05) in cumulus cell-enclosed oocytes after LH exposure during IVM but was unchanged after exposure to either FSH or thyroid-stimulating hormone when compared to control treatments (0.23 +/- 0.01, 0.20 +/- 0.02, 0.19 +/- 0.01 vs. 0.16 +/- 0.02 nmol 14CO2/micrograms protein/3 h, respectively). Pyruvate metabolism was not different between LH and control treatments. Evidence demonstrated that LH acts via the cumulus cells to increase glutamine metabolism within intact cumulus cell enclosed oocytes and in mature oocytes denuded after LH exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485247 TI - In vitro phosphorylation sites of stallion and bull P1-protamines for cyclic adenosine 3',5'-monophosphate-dependent protein kinase and protein kinase C. AB - Fish and mammalian protamines are phosphorylated after their synthesis during sperm cell maturation. Cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC), both requiring basic amino acids at their recognition sites, have previously been found to phosphorylate fish protamines in vitro. In this study, these enzymes were used to phosphorylate stallion and bull sperm P1-protamines in vitro. A species-specific difference was found, since PKA was able to phosphorylate both protamines while PKC phosphorylated only stallion protamine. Thr-41, the only threonine residue in stallion P1-protamine, and most probably the homologous Thr-43 in bull P1-protamine are the sites for PKA phosphorylation in addition to an internally located Ser-29 present only in stallion protamine. This Ser residue was phosphorylated in vitro by both kinases. Protamine phosphorylation by PKA was found to be almost independent of cAMP and was inhibited only by a tenfold concentration of PKI when compared to phosphorylation of a model peptide, kemptide. Addition of calcium, phosphatidylserine, and diolein caused a twofold stimulation in phosphorylation of stallion protamine by PKC, indicating that specific cofactors of PKC may have a role in mammalian protamine phosphorylation. We suggest that PKA is a good universal candidate for in vivo phosphorylation of P1-protamines. PMID- 8485248 TI - Effect of neonatal diethylstilbestrol exposure on luteinizing hormone secretion following ketamine anesthesia and gonadotropin-releasing hormone in castrated postpubertal rats. AB - Neonatal diethylstilbestrol (DES) exposure diminishes pituitary responsiveness to GnRH in castrated postpubertal rats 4 h after placement of intra-atrial cannulae under ketamine anesthesia. Ketamine anesthesia has been reported to blunt the preovulatory LH surge in female rats and to decrease baseline LH levels in males immediately following administration, although its effect lasted less than 2 h. It is not known what impact ketamine has on baseline LH levels or on GnRH stimulated LH release in estrogen-exposed castrated rats. This study was designed to determine 1) whether the changes in GnRH-induced LH secretion in DES-exposed castrated rats are partially attributable to a direct effect of ketamine; 2) the gender-specific effects of ketamine on LH secretion; and 3) the DES-dependent effects of ketamine on LH secretion. In this experiment we ascertained the effect of ketamine anesthesia for right heart cannulation on LH levels in male and female 42-day-old castrated rats that were exposed to either corn oil or DES (0.1 microgram/day) on Days 1 through 10 of life. LH secretion in DES-exposed animals increased, in contrast to that in control animals, immediately (< 10 min) after anesthesia and cannulation. Mean LH levels in DES-exposed females were lower than in controls before GnRH administration and were blunted following GnRH. While ketamine and catheterization were associated with decreased LH titer in males, the extent of that decrease was not dependent on exposure to DES. Both sexes and exposure groups achieved baseline catheter LH values by 4 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485249 TI - Glycine and alanine supplementation of culture medium enhances development of in vitro matured and fertilized cattle embryos. AB - One-cell cattle embryos were prepared by in vitro oocyte maturation and fertilization (IVM/IVF) and cultured with or without oviductal cells. Embryos were evaluated after 7 days in culture to determine the percentage developing from the 1-cell stage to the morula or blastocyst stage. The combination of glycine (2 mM) and alanine (1 mM) with oviductal cells (experiment 1) improved embryo development over that in control culture (29 vs. 13%; p < 0.05). An optimum response was obtained with 10 mM glycine and 1 mM alanine in coculture (experiments 2 and 3). In experiment 4, the effects of glycine (0 or 10 mM), alanine (0 or 1 mM), and the presence or absence of oviductal cells were tested. In the absence of oviductal cells, the addition of glycine, alanine, or glycine and alanine combined improved embryonic development over that in control medium (45, 33, 42 vs. 24%, p < 0.001, p < 0.05, p < 0.001, respectively). However, the effect of the combination of glycine and alanine was not different from that of glycine alone when oviductal cells were absent (42 vs. 45%, p > 0.10). In the presence of oviductal cells, glycine or the combination of glycine and alanine improved embryonic development over that in the control medium with cells (47, 55 vs 37%, p < 0.01, respectively). However, supplementation with alanine alone gave no improvement over controls when oviductal cells were present (40 vs. 37%, p > 0.10). These results indicate that glycine and alanine, when used independently, directly affect cattle embryo development, but in combination affect embryo development indirectly, possibly by altering oviductal cell function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485250 TI - Induction of acrosome reactions of canine sperm by homologous zona pellucida. AB - In this study the induction of the acrosome reaction of canine sperm by homologous zona pellucida (ZP) was examined. Twelve semen samples obtained from 6 normal beagle dogs were evaluated after sperm incubation in vitro with canine capacitation medium (CCM). Washed sperm were preincubated at 37 degrees C in 5% CO2 in air for 4 and 7 h prior to experimental treatment. Sperm were co-incubated for 1 min with intact oocytes collected from canine ovaries. Half of the oocytes were then fixed, and the bound sperm were assessed for acrosome reactions through use of a polyclonal antisperm antiserum and indirect immunofluorescence. The remaining oocytes were incubated in sperm-free medium for an additional 1-h period, and the acrosomal status of sperm bound to the ZP was evaluated similarly. The percentage of acrosome-reacted sperm on the ZP increased significantly during the 1-h incubation period. In other experiments, capacitated canine sperm were incubated with heat-solubilized ZP for 1 h and their acrosomal status was determined using fluoresceinated Pisum sativum lectin. The percentages of acrosome-reacted sperm increased significantly in ZP solution compared with controls. These data demonstrate that intact and solubilized canine ZP are capable of inducing acrosome reactions of canine sperm. PMID- 8485251 TI - De novo protein synthesis by bovine uterine tube (oviduct) epithelial cells changes during co-culture with bull spermatozoa. AB - Polypeptides secreted by uterine tube epithelial cells (UTEC) may facilitate sperm cell capacitation in vivo. This experiment evaluated the effect of sperm UTEC co-culture on de novo protein synthesis by epithelial cells of the tubal isthmus. Comparisons of the patterns of proteins secreted into medium were made between four culture groups incubated for 24 h in the presence of 35S-methionine: group 1, sperm cells alone; group 2, control UTEC monolayers; group 3, UTEC co cultured with sperm cells; and group 4, UTEC partitioned by a diffusible membrane from sperm cells during culture. Two-dimensional PAGE followed by fluorography was used to analyze conditioned medium containing secreted proteins from each group. The experiment was replicated four times. Sperm cells alone secreted no detectable proteins, whereas control UTEC monolayers produced a wide array of polypeptides. Sperm cells attached to UTEC in co-culture within minutes, and the resultant protein profile for these UTEC differed markedly from that of the control UTEC. Several new proteins were seen only from co-cultured cells, whereas other protein groups that were present with UTEC alone were absent in the co culture medium of group 3. The protein pattern expressed by UTEC partitioned from sperm cells (group 4) was intermediate between that of the group 2 controls and that of co-cultured UTEC (group 3). In summary, the attachment of sperm cells to the UTEC during co-culture changed the types and quantities of proteins secreted into the conditioned medium as compared to those of control UTEC monolayers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485252 TI - Differential gonadotropin responses to N-methyl-D,L-aspartate in metestrous, proestrous, and ovariectomized rats. AB - Peripheral administration of N-methyl-D,L-aspartate (NMA), an analogue of the excitatory amino acid aspartate, elicits LH and prolactin (PRL) release in rats, most likely by increasing endogenous releasing-hormone secretion. These experiments were carried out to assess the degree to which NMA stimulates FSH and to analyze the relationship between endocrine status and responsiveness to NMA in female rats, in contrast to male rats, as described in the companion paper [Biol Reprod 48:000-000]. In experiment 1, estrous rats (n = 10) and diestrous rats (n = 10) and in experiment 2, estrous rats (n = 11) and rats ovariectomized (OVX) 8 days previously (n = 10) were fitted with atrial catheters and injected s.c. with 100 micrograms of an LHRH antagonist or vehicle at 2100 h. Starting at 0900 h the next day (metestrus, proestrus, or Day 9 post-OVX), blood was withdrawn every 10 min for 3 h. Each animal received i.v. 5 mg NMA after the first hour and i.v. 500 ng LHRH after the second hour. NMA significantly increased LH in metestrous and proestrous females, and LHRH antagonist blunted the increases. In OVX females, LH decreased after NMA. FSH was not affected by NMA in any group. PRL increased after NMA in proestrous and metestrous animals. LHRH caused surge-like LH and small FSH increases in vehicle groups; these increases did not differ in amplitude between intact and OVX animals and were blunted by pretreatment with LHRH antagonist. In experiment 3, 10 diestrous rats were fitted with atrial catheters and were serially bled at 2-h intervals from 1200 h on the following day (proestrus) until 0600 h on estrus morning. After the first sample the animals were injected s.c. with 0.2 mg/kg MK801, a noncompetitive NMA receptor antagonist, or with saline. Four of the 5 saline-treated animals exhibited surges of LH and FSH as well as elevated progesterone levels, with LH and progesterone peaking at 2000 h. Five of 5 MK801-treated animals failed to have elevated LH, FSH, or progesterone levels at any time point. These data demonstrate that LHRH mediates the LH response to NMA in rats and that endogenous NMA receptor binding may be necessary for the preovulatory gonadotropin surges. The lack of FSH responses to NMA during periods of low-level gonadotropin secretion suggests that physiological increments in endogenous LHRH secretion sufficient to induce a pulse of LH are insufficient to stimulate pulse-like FSH release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8485253 TI - Differential gonadotropin responses to N-methyl-D,L-aspartate in intact and castrated male rats. AB - Peripheral administration of N-methyl-D,L-aspartate (NMA), a neuroexcitatory amino acid agonist, probably stimulates LH release through an increase in endogenous LHRH secretion. In the present study, NMA and a potent LHRH antagonist were used to determine the degree to which release of FSH is similarly dependent upon the acute secretion of LHRH. A second aim was to compare responsiveness of LHRH neurons to NMA in castrated and intact male rats. Adult male rats were castrated (n = 10) or sham castrated (n = 11) on the morning of Day 0. After 8 days, rats were fitted with atrial catheters between 0900 and 1200 h; at 2100 h they received s.c. either oil vehicle or 100 micrograms of an LHRH antagonist. Starting at 0900 h on Day 9, 0.5-ml blood samples were collected every 10 min for 3 h. After 1 h of sampling each animal received i.v. 5 mg of NMA in 0.5 ml 0.9% saline. An hour later each rat received i.v. 500 ng of LHRH in 0.5 ml saline. Plasma LH, FSH, and prolactin (PRL) levels were determined by RIA. In the oil treated sham castrates, mean plasma LH levels were increased by 110% (p < 0.01) within 10 min and remained elevated for 30 min after the injection of NMA. The profile of this LH secretory response was similar to or slightly more robust than endogenous LH pulses observed previously. The NMA-induced LH release was completely blocked by pretreatment with LHRH antagonist. In both oil- and antagonist-treated sham-castrated rats, NMA administration failed to elicit a concomitant increase in plasma FSH levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485254 TI - Catecholamines stimulate testicular steroidogenesis in vitro in the Siberian hamster, Phodopus sungorus. AB - We have examined direct effects of catecholamines on testicular testosterone production in a seasonally breeding species, the Siberian hamster, Phodopus sungorus. Testicular parenchyma from gonadally active long photoperiod (LD) exposed and gonadally regressed short photoperiod (SD)-exposed animals was incubated for 6 h with norepinephrine, epinephrine, beta-adrenoceptor agonist isoproterenol, or alpha-adrenoreceptor agonist phenylephrine (all at 10 microM), as well as with various concentrations of norepinephrine (10 nM-10 microM), and 10 microM norepinephrine with or without hCG (0.7, 3.1, and 12.5 mIU/ml). In addition, effects of alpha-adrenoreceptor antagonist prazosin and beta adrenoreceptor antagonist propranolol (50 microM) were tested in the incubations containing 10 microM norepinephrine. In the incubations of testes from both LD and SD Siberian hamsters, norepinephrine was most effective in stimulating testosterone production, followed by epinephrine and phenylephrine, while isoproterenol failed to increase testosterone accumulation. The stimulatory effects of norepinephrine were dose-dependent and were prevented by coincubation with prazosin, but not affected by coincubation with propranolol. In combination with various doses of hCG, norepinephrine failed to stimulate testosterone production above the levels obtained with hCG alone. These data indicate that the testicular receptors mediating the action of catecholamines on testicular steroidogenesis in Phodopus sungorus are of the alpha 1-subtype, a result in accordance with a previous study in the golden hamster. However, the results of the present study are strikingly different from the findings obtained in the golden hamster in terms of the effects of photoperiod on the responsiveness of testicular steroidogenesis to catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485255 TI - Effects of chimerism in sheep-goat concepti that developed from blastomere aggregation embryos. AB - Chimeric sheep-goat pregnancies were established in 24 ewes and 29 does by transferring 251 embryos, prepared by the blastomere-aggregation technique, to 52 ewes and 61 does. Fifteen does experienced early pregnancy failure; however, term offspring were delivered by 24 ewes (17 lambs, 3 kids, 6 chimeras) and 14 does (6 lambs, 9 kids, 6 chimeras). (Fetal classifications were based on phenotype, red blood cell isozymes, and lymphocyte antigen expression). RIAs for ovine and caprine placental lactogen detected chimerism in the binucleate cell population of the trophoblast throughout the pregnancies of 2 ewes and 7 does; these pregnancies resulted in the birth of 12 healthy offspring. Histological examinations of intact placentomes from 2 of these recipients revealed a continuous cellular trophoblast apposed to a syncytium as in normal placentas. Chimerism was detected electrophoretically in the membranes of the placentas with binucleate cell chimerism and in 17/28 of the other placentas. Data collected on placental lactogen production, chimerism in the conceptus, and placental morphometry were examined with respect to the stages of the blastomeres aggregated to form the chimeric embryo and with respect to fetal status at delivery. For comparison, analogous data were collected on sheep-goat concepti that developed from embryos prepared by inner cell mass transplantation. PMID- 8485256 TI - Uterine extracellular fluid volume and blood flow after artificial uterine stimulation to rats differentially sensitized for the decidual cell reaction. AB - Uterine extracellular fluid volume (ECFV) and blood flow (BF) were assessed after unilateral intrauterine injection of sesame oil to rats given either ideal sensitization for the decidual cell reaction or one of several forms of non-ideal sensitization. The study was intended to determine how changes in uterine ECFV and BF might contribute to the Evans blue dye reaction that can be elicited during early decidualization. Uterine ECFV was determined by the uterine volume of distribution of 51Cr-EDTA after its i.v. injection; BF was determined by the radioactive microsphere technique. ECFV was significantly greater in oil-injected than in control horns by 8 h after deciduogenic stimulation, reaching a maximum of 0.63 +/- 0.06 microliter/mg (p < 0.05) in oil-injected horns at 16 h. Ideal temporal sensitization and sensitization with estrogen both were essential to obtain the significantly increased ECFV in stimulated horns. Although absolute uterine BF increased to oil-injected horns, the increase matched uterine weight gains, making relative uterine BF similar for both horns (3-4 microliters/min/mg) at all times after unilateral deciduogenic stimulation. Ideal sensitization did not significantly alter the relative uterine BF. The increase in ECFV occurs at a similar time and requires the same ideal sensitization as the stimulation-induced increase in endometrial vascular permeability described previously, suggesting that these events are under similar control. We suggest that enzymatic changes to the uterine extracellular matrix may contribute to the Evans blue reaction by creating a larger compartment into which protein-dye complexes may diffuse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485257 TI - Hypothalamus-pituitary-ovarian axis in cyclic rats lacking progesterone actions. AB - Antagonizing diestrous progesterone actions in cyclic rats by s.c. injections of the antiprogesterone RU486 (2 mg twice a day from metestrus through proestrus) increased LH and decreased FSH basal serum concentrations. Ovariectomy at metestrus (0800 h) increased serum levels of both gonadotropins in controls and reversed the RU486-induced dissociation of basal gonadotropin secretion. RU486 dissociated gonadotropin secretion is also dependent upon LHRH, since treatment (s.c.) with 1 mg GnRH antagonist (ORG 30276) twice a day on metestrus and diestrus completely prevented both the RU486-induced increase in LH and the decrease in FSH serum concentrations. The LHRH content in the medial basal hypothalamus and median eminence increased on proestrous morning in RU486-treated rats. The LH pituitary response to an exogenous i.v. bolus of 25 ng LHRH (Peninsula 7201; Peninsula Laboratory, Inc., Merseyside, UK) at 1700 h on diestrus was enhanced in rats treated with RU486. No differences in pituitary FSH response were noted with respect to oil-injected rats. The pituitary content of both gonadotropins decreased in RU486-treated rats on proestrous morning. All these effects due to RU486 in cyclic rats were reversed by ovariectomy. Testosterone serum levels increased significantly from diestrus onward, and the estradiol concentration increased on proestrous morning in RU486-treated rats. Ovariectomy as well as LHRH antagonist treatment eliminated the effects of RU486 on ovarian steroid production. Moreover, antiestrogen tamoxifen treatment reversed RU486-dissociated gonadotropin secretion, while antiandrogen flutamide treatment had no effect. The results of this experiment have confirmed previous findings that RU486 treatment dissociates basal gonadotropin secretion in cyclic rats. In addition, the present results show that: (1) this effect of RU486 is not due to a direct effect of this compound or to the blockade of progesterone action at a central level; (2) the effect of RU486 on pituitary gonadotropin secretion depends on ovarian substances other than progesterone and LHRH, since it is reversed by ovariectomy and completely abolished by LHRH antagonist treatment; (3) the reduction in FSH serum levels in rats treated with RU486 seems to be exerted by inhibin and estradiol at the pituitary level by reducing FSH synthesis and secretion; and (4) the hypersecretion of LH in rats treated with RU486, as compared to that resulting from ovariectomy, seems to be the consequence of, first, a lack of progesterone inhibitory action on LH secretion, and, second, an inappropriate feedback system involving increased hypothalamic LHRH activity and pituitary sensitivity to LHRH of moderately high levels of estradiol in the presence of abnormally high levels of testosterone. PMID- 8485258 TI - Long-term effect of a urinary chemosignal on reproductive fitness in female mice. AB - The effect of synthetic 2,5-dimethylpyrazine (a compound naturally produced by grouped females) on the overall reproductive success of female mice was investigated. The exposure of tested females to control or experimental stimuli began on the day of birth and lasted throughout maturation, mating, pregnancy, and the lactating of their first litters. Females exposed to this urinary compound attained their first estrus significantly later than the animals exposed to water only. On average, the prepubertal, exposed females reached puberty 3.7 to 3.9 days later than the unexposed animals. The females in which puberty was delayed by this synthetic chemosignal did not show a single fully completed estrous cycle before the age of 35 days. Only 52-64% of exposed females successfully bred and reared their litters as compared to 86-96% of the unexposed, control females (p < 0.05). A significantly higher mortality of pups associated with 2,5-dimethylpyrazine exposure during lactation was observed. The reproductive deficit displayed by females born into a 2,5-dimethylpyrazine environment is qualitatively similar to the effect observed in dense populations, in both laboratory and free-living conditions. PMID- 8485259 TI - Effects of decidual cell supernatants and lymphokines on murine trophoblast growth in vitro. AB - Blastocysts were flushed from CD1 mice and were cultured in plastic or laminin coated plates as an in vitro model of implantation. The purified cytokines epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) markedly stimulated 3H-thymidine incorporation; but recombinant murine granulocyte macrophage colony-stimulating factor (GM-CSF), which might be produced by alloantigen-stimulated T cells at the feto-maternal interface, had no growth stimulating effect. Indeed, higher nonphysiological concentrations of GM-CSF manifested a toxic inhibition. Surprisingly, a purified nonrecombinant murine GM CSF preparation induced proliferation of both blastocyst and ectoplacental cone trophoblast whereas recombinant murine (and human) GM-CSF had no effect, indicating that the growth stimulation may have been due to a contaminant. Decidual supernatants prepared on Days 5.5-6.5 of pregnancy from mice with high abortion rates (DBA/2-mated CBA/J) had no toxic or stimulating effect on blastocyst trophoblast outgrowth compared to similarly prepared supernatants from low-abortion-rate DBA/2-mated C3H/HeJ mice. These data suggest that it is not GM CSF that is crucial for the trophoblast proliferation that determines the success of pregnancy. PMID- 8485260 TI - The African-American cancer crisis, Part II: A prescription. AB - To appreciate the causes of the African-American cancer crisis, contemporary myths and perceptual gaps regarding cancer in blacks must be analyzed and placed in historical context. Since ancient times, racism has permeated western scientific, medical, and social cultures. Yet contemporary analysts typically frame a 370-year-old African-American health deficit in nonracial terms, and ignore both the metamorphosis of racism and the impact of racism on the prevention, diagnosis, and treatment of cancer; exposure to cancer-causing industrial pollutants; educational opportunities for black health professionals and policymakers, and other factors. If the African-American cancer crisis is to be halted, the growing divergence between urgent needs and meager resources devoted to preventing, detecting, and treating cancer in blacks must be sharply reversed. PMID- 8485261 TI - The effectiveness of Florida's "Improved Pregnancy Outcome" program. AB - The development of a national program to assure access to prenatal care for all women, regardless of income, is believed to be an effective means of reducing low birthweight and neonatal mortality in the U.S. Yet scarce empirical evidence concerning the effectiveness of large-scale prenatal care programs is available. This paper summarizes an evaluation of a statewide public prenatal care program which grew out of the federal Improved Pregnancy Outcome (IPO) project. Using linked birth and infant death-certificate data, and IPO program records from a four-year period (1985-1988), this study compares the neonatal mortality rates of participants of Florida's IPO program with those of a matched comparison group. The results indicate an inverse relationship between IPO participation and the risk of neonatal mortality in a low-income population. These findings suggest that large-scale prenatal care programs can be effective in improving birth outcomes. PMID- 8485262 TI - No more "Let them eat admonitions": the Clinton Administration's emerging approach to minority health. AB - The startling health disparities between whites and racial and ethnic minorities in the United States are partly the result of six major assumptions about health promotion that permeated the Reagan and Bush Administrations. These assumptions, which placed the responsibility for maintaining health on individual Americans, are consistent with policymakers' reliance on market forces to address social issues. While this model may serve persons with a continuum of options and resources to elicit change, it does not benefit the underserved. In contrast, the Clinton Administration's approach, rooted in broad-based participation and multisector planning, is consistent with international models and promises long overdue recognition that health problems in underserved communities stem from poverty--not the poor. PMID- 8485263 TI - The African-American cancer crisis, Part I: The problem. AB - Over the past 40 years, increasing numbers of Americans have benefited from cancer prevention, early detection, and improved treatment. But a review of site specific cancer data from 1950 to the present shows that contemporary African Americans have the highest age-adjusted rates of cancer incidence and mortality of any racial or ethnic group in the United States. Compared to whites, blacks have significantly higher incidence rates for cancers of the lung, prostate, breast (under age 40), colon, pancreas, esophagus, cervix, larynx, stomach, and multiple myeloma. Blacks have significantly higher mortality rates for cancers of the lung, prostate, breast (all ages), colon, pancreas, esophagus, cervix, uterine corpus, larynx, stomach, and multiple myeloma. Moreover, the gap between whites and blacks is widening dramatically. These startling statistics suggest that cancer researchers and policymakers, and the institutions they represent, may not fully appreciate the black cancer experience. PMID- 8485264 TI - Review article: immunosuppressive therapy for inflammatory bowel disease. AB - Refractory inflammatory bowel disease can be treated by surgery or using nutritional supplementation or replacement. Immunosuppressive agents may also play a role for refractory disease; they have gained widespread acceptance, due not only to trials that demonstrate efficacy but also to the realization that these side-effects are minor compared to those associated with long-term, high dose corticosteroids. To date, 6-mercaptopurine and azathioprine remain the drugs of choice based upon extensive clinical experience, but both methotrexate and cyclosporin are promising immunosuppressants for otherwise refractory disease. PMID- 8485265 TI - Review article: topical corticosteroids in inflammatory bowel disease. AB - It would be ideal to treat inflammatory bowel disease with topical corticosteroids that are either not absorbed through the mucosa, or have a substantial first-pass hepatic metabolism. The topical use of hydrocortisone, prednisolone-21-phosphate or betamethasone is often associated with systemic side effects. Newer corticosteroid preparations (prednisolone metasulphobenzoate, tixocortol pivalate, fluticasone propionate, beclomethasone dipropionate and budesonide) are usually associated with minimal systemic corticosteroid activity. This article reviews the clinical activity and safety of these newer preparations. PMID- 8485266 TI - Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials. AB - To define better the efficacy of bile acid therapy for dissolution of radiolucent gallstones, we performed a meta-analysis of published trials from January 1966 to September 1992. Studies were identified using a MEDLINE computer search followed by an extensive manual search. The inclusion criteria used were: randomized trial, radiolucent gallstones in a visualizing gallbladder on oral cholecystography, and complete stone dissolution confirmed by oral cholecystography or ultrasound. Study results were pooled into 6 groups: placebo: high- and low-dose chenodeoxycholic acid (CDCA) (> or = 10 mg.kg/day and < 10 mg.kg/day); high- and low-dose ursodeoxycholic acid (UDCA) (> or = 7 mg.kg/day and < 7 mg.kg/day) and combined CDCA plus UDCA. Homogeneity calculations were performed and the percentage of complete stone dissolution calculated for each group with 95% confidence intervals. Of 66 trials identified, 23 comprising 1949 patients met the inclusion criteria. A total of 1062 patients were treated with CDCA, 819 with UDCA and 78 combination therapy. In studies > 6 months' duration, high-dose UDCA completely dissolved stones in 37.3% of patients (95% C.I. 33 42%), low-dose UDCA in 20.6%) and high-dose CDCA 18.2% (95% C.I. 15-21%). Based on only two studies, combination therapy achieved dissolution in 62.8% (95% C.I. 51-74%) of patients. Stones less than 10 mm dissolved significantly more frequently than stones larger than 10 mm. This analysis shows that UDCA in doses greater than 7 mg.kg/day taken for greater than 6 months will dissolve radiolucent gallstones in 38% of patients. The combination of UDCA and CDCA may be more efficacious but this observation is based upon only 78 patients and requires confirmation in further randomized trials. PMID- 8485267 TI - Two-week eradication regimen for metronidazole-resistant Helicobacter pylori. AB - At present there is no generally accepted treatment regimen for eradicating metronidazole-resistant Helicobacter pylori. This study determines the eradication rate after treatment with 40 mg omeprazole o.m. and 500 mg amoxycillin q.d.s. for 14 days, with 120 mg tripotassium dicitrato bismuthate q.d.s. for the first week (Days 1-7) and 750 mg ciprofloxacin b.d. for the second week (Days 8-14). Thirty patients (16 male, mean age 45 years, range 16-80 years) with duodenal ulcers (n = 18) or non-ulcer dyspepsia (n = 2) and metronidazole resistant H. pylori detected by histology, culture, in vitro sensitivity tests and a positive 13C-urea breath test entered the study. Follow-up was by 13C-urea breath test at the end of treatment and at 1, 3, 6, and 12 months. Eradication was defined as a negative 13C-urea breath test at least 1 month after finishing treatment. H. pylori was successfully eradicated in 21/30 (71%) patients (median follow-up 10.2 months, range 4-12 months). A pre-treatment ciprofloxacin resistant strain was isolated in 1/9 patients in whom eradication failed. Of 30 patients 29 completed the 2-week regimen; one patient experienced dizziness after 3 days of treatment. The most common side-effect was increased stool frequency (n = 6). This 2-week treatment regimen for metronidazole-resistant H. pylori is well tolerated and achieves an eradication rate of 70%. PMID- 8485268 TI - Oral tobramycin in ulcerative colitis: effect on maintenance of remission. AB - Oral tobramycin for 7 days has been shown to be of benefit as an adjunct to conventional medication in acute ulcerative colitis. Eighty-one patients (40 who had received tobramycin; 41 placebo) who had been enrolled in a double-blind placebo-controlled trial of this drug in acute disease were subsequently followed to determine whether this short-term benefit persisted. Relapse was defined as a liquid stool frequency of three times daily with rectal bleeding. Results were analysed by the log-rank test on Kaplan-Meier survival curves. Treatment failure was defined as a lack of response by the end of the acute trial period, or subsequent relapse. In a second analysis, only those entering remission at the end of the acute trial were considered, and followed to relapse. Although at the start of the follow-up period significantly fewer patients in the tobramycin group had failed (failed: tobramycin 9, placebo 24; not failed tobramycin 31; placebo 17; P = 0.001), the failure-free survival curves subsequently converged and did not differ significantly. After 1 and 2 years, the failure-free survival rates were 40% (S.E. = 7.8%) and 20% (S.E. = 6.3%) for the tobramycin group and 24% (S.E. = 6.7%) and 12% (S.E. = 5.1%) for the placebo group. When only those entering remission were considered, there was no significant difference in the relapse rates in the two groups. Benefit from tobramycin is therefore short-lived and may reflect short-term changes in the faecal flora. PMID- 8485269 TI - A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis. AB - In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red-cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three-fold and at 6 months by four fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red-cell membrane concentrations of dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell-membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit. PMID- 8485270 TI - Efficacy of long-term therapy with low doses of omeprazole in the control of gastric acid secretion in Zollinger-Ellison syndrome patients. AB - Thirteen patients with Zollinger-Ellison syndrome were investigated: 8 without, and 5 with, previous gastric surgery. After 7-34 months of treatment with famotidine, 8 out of 13 patients were resistant to this drug. Omeprazole 60 mg/day was administered to these 8 patients; after one month, the dose was reduced to 40 mg/day, and after another month to 20 mg/day. Basal acid secretion was inhibited by every dose of omeprazole. The patients were then treated with a low dose (20 mg/day) of omeprazole for a longer period. Periodic clinical and endoscopic assessments, and measurement of basal acid secretion showed the efficacy of this low dose of omeprazole in our Zollinger-Ellison syndrome patients. The drug was discontinued after 12-32 months of omeprazole treatment, and gastric acid recovery was evaluated. Four patients recovered 50% of their 'initial basal acid secretion' after 5 days, while two patients who had been treated with omeprazole for a longer time (30-32 months) recovered only 38 and 40%, respectively, of their 'initial basal acid secretion' at the tenth day. Our results indicate that the omeprazole dosage to be used in the treatment of Zollinger-Ellison syndrome must be chosen principally on the basis of basal acid secretion determination. A low daily dose of omeprazole is able to control acid secretion in Zollinger-Ellison syndrome for a long period (10-30 months). The slow recovery of gastric secretory function demonstrates the prolonged inhibitory effects of omeprazole. PMID- 8485271 TI - Cisapride in the treatment of gastro-oesophageal reflux disease. AB - Prokinetic agents are being used increasingly in medical therapy for gastro oesophageal reflux disease (GERD). This study examined the effect of 10 mg q.d.s., oral cisapride, or placebo, taken for 12 weeks, on 48 patients with symptoms and endoscopic evidence of GERD. Objective evaluation of benefit was obtained by endoscopy and biopsy, oesophageal manometry, acid reflux provocation test and 24-h oesophageal pH monitoring. Cisapride significantly increased lower oesophageal sphincter pressure (P = 0.003) against baseline and also against placebo, in patients (n = 9) with an hypotensive lower oesophageal sphincter pressure (P < 0.01). The frequency of dyspeptic symptoms was significantly improved in the cisapride group (P = 0.03). Antacid intake, global evaluation of symptoms and a VAS score for symptoms were all better than placebo but failed to reach significance (global evaluation by patients, P = 0.07). Overall, there was no significant improvement in oesophagitis at either 6 weeks (P < 0.05 > 0.3) or 12 weeks (P = 0.07). However, if patients with grades I and II oesophagitis at entry were excluded, cisapride had a significantly greater effect than placebo, 6 weeks (P = 0.05), 12 weeks (P = 0.04). In those with oesophageal ulceration, cisapride was significantly more effective than placebo in inducing healing. Gastro-oesophageal reflux was very variable on both 24-h pH monitoring and acid reflux provocation test. In spite of a 50% decrease in acid exposure on 24-h pH monitoring (cisapride group, mean % pH < 4 day: entry 18.9%, 12 weeks 9.6%), there were no significant intra- or intergroup differences for percentage of time < pH 4, or frequency and duration of episodes, neither pre- or post-prandially, day or night, except for the number of post-prandial episodes during acid reflux provocation tests, which decreased significantly more with cisapride than with placebo (P < 0.05). Thus, oral cisapride when taken for 12 weeks promoted healing of oesophagitis and improved symptoms in patients with GERD; although an increase in lower oesophageal sphincter pressure was observed and a reduction in acid reflux was measured, no significant decrease of acid exposure was seen. PMID- 8485272 TI - The effects of lansoprazole, 30 or 60 mg daily, on intragastric pH and on endocrine function in healthy volunteers. AB - Seven days of dosing with either 30 mg or 60 mg of lansoprazole were compared with placebo in a double-blind, randomized, three-way cross-over study in 12 male healthy volunteers. Twenty-four-hour intragastric pH was measured after 7 days of dosing with each regimen, as well as 3 and 7 days after the end of dosing. During dosing with placebo, intragastric pH was above 4 for a median of 51 minutes. pH values were significantly raised to above 4 for 8.45 and 8.33 hours on Day 7 of dosing with lansoprazole 30 and 60 mg, respectively, but returned to normal by the third day after stopping dosing. No clinically relevant influence on endocrine function (serum concentrations of insulin, aldosterone, testosterone, parathormone, glucagon, T3, T4, TSH, LH, FSH, STH, prolactin, circadian cortisol profile, ACTH test) was observed. No serious adverse clinical or laboratory events were noted. PMID- 8485273 TI - Ileo-caecal ulceration associated with the use of diclofenac slow release. AB - A 38-year-old man with seropositive arthropathy on long-standing treatment with diclofenac slow release presented with abdominal pain, diarrhoea and anaemia. Upper gastrointestinal endoscopy and barium series were unremarkable. Five months later he presented with a right iliac fossa mass. Investigations revealed discrete ulceration in the terminal ileum and caecum confirmed at laparotomy. Other possible causes of intestinal ulceration were excluded suggesting a diagnosis of non-steroidal anti-inflammatory drug associated intestinal ulceration. PMID- 8485274 TI - Effect of methylprednisolone on small bowel, spleen and liver changes in a murine model of inflammatory bowel disease. AB - The aim of this study was to evaluate the influence of methylprednisolone (1 mg/kg, i.p.) on inflammatory lesions in the small bowel, liver (pericholangitis) and spleen (lymphofollicular proliferation), in a model of inflammatory bowel disease induced by 2.4-dinitrofluorobenzene in previously sensitized BALB-c mice. As a parameter of corticosteroid anti-inflammatory and immunosuppressive action, we simultaneously investigated its effects on mononuclear cell accumulation within the ileal lamina propria and submucosa during the observed time period (1 30 days). We noted a significant decrease in accumulation of mononuclear cells within the lamina propria (P < 0.001). An effect on mononuclear cell infiltration within the ileal submucosa was also noted but was not statistically significant. In addition, pericholangitis in the liver and lymphofollicular proliferation in the spleen were not observed in the experimental group during treatment with methylprednisolone. The results of this study indicate that the previously described model of intestinal inflammation could be used in further research of present and new therapeutic modalities for inflammatory bowel disease. PMID- 8485275 TI - Rolling review: upper gastrointestinal bleeding. PMID- 8485276 TI - Short report: effect of ranitidine on duodenal ulcer healing in patients with cirrhosis of the liver. AB - The effect of ranitidine (300 mg daily) on the healing of acute duodenal ulcer was investigated in patients with and without cirrhosis of the liver. Of the 109 patients who entered the study, two patients from each group were excluded. Healing rates after 4 and 8 weeks were significantly different between patients with cirrhosis and controls (4- and 8-week healing rates in cirrhotics and non cirrhotics: 49 and 69%, and 71 and 91%, respectively). This study demonstrates that duodenal ulcer healing is delayed in patients with cirrhosis. PMID- 8485277 TI - [Transjugular intrahepatic portosystemic shunt]. PMID- 8485278 TI - [A prognostic multifactorial study of sepsis in an internal medicine service]. AB - All cases of sepsis attended at the Service of Internal Medicine from 1985 to 1989, both inclusive, were retrospectively analyzed by the statistical study of several clinical, epidemiological, bacteriological and laboratory factors. The parameters acting as prognosis factors were analyzed using Cox's method of logistic regression, in order to obtain more reliable information on the multifactorial spectrum determining "death due to sepsis". The unifactorial analysis (UFA) suggested that the following factors were associated to an statistically significant increase in the mortality due to sepsis: age above 70; male sex; presence of shock upon hospitalization; nosocomial etiology; high levels of urea, creatinine and LDH; proteinuria; family of the causal germ (gram positive coccus) and underlying pathology. The relative risks (RR) or "odd ratios" of creatinine and LDH were, respectively, 2.8 and 2.9 in the UFA; 3 and 3.3 in the multivariant analysis (MVA). In the older patients developing sepsis within their communities, RR were respectively 2.7 and 1.98 in the UFA and 1.1 and 2.7 in the MFA. The results of the univariant and multivariant analysis showing the relative risk (odd ratio) associated to each of these variables with statistical significance, demonstrate that the mortality rate due to sepsis increases with age, nosocomial etiology and elevation of creatinine and lactodehydrogenase (LDH) levels. We stress the great importance of the LDH as a prognostic factor of sepsis. PMID- 8485279 TI - [The value of pulse oximetry during the performance of a forced spirometry maneuver]. AB - Given that forced spirometry is the main routine exploration in any laboratory of pulmonary functional assessment, we have analyzed the behaviour of O2 arterial saturation (SaO2) during such maneuver in patients with airflow chronic obstruction (AFCO), in order to verify any potential alterations. We have studied three groups of patients: Group A, control, 17 healthy subjects; group B, 18 patients with AFCO and initial saturation higher than 90%; group C, 15 patients with AFCO and saturation equal to or lower than 90%. Total duration of the maneuver was significantly higher in groups B and C compared with the control group (p < 0.001). In groups A and B, we did not observed any significant reductions in SaO2 with respect to the initial value, although we did observed such differences in group C (p < 0.001). None of the patients presented a subjective clinical disorder, although the absence of both complexity and risk suggest the convenience of including the oximetry as an additional parameter when conducting a forced spirometry in patients with AFCO and respiratory failure. PMID- 8485280 TI - [The indications for the antipneumococcal vaccine in Spain]. AB - The anti-pneumococcal vaccine, with 23 capsular polysaccharides, is an effective vaccine used in most of the developed countries, although still not commercially available in Spain. Between January 1981 and June 1992, we isolated 784 Streptococcus pneumoniae from clinical samples (excluding asymptomatic carriers), 728 of which could be serotyped (300 isolated in hemoculture and/or LCR). 91.5% of the total and 93.3% of the most invasive strains, as well as 98.1% of the penicillin-resistant strains or 98.8% of the isolated multiresistant strains, presented a serotype covered by the current vaccine. The high resistance to antibiotics of the pneumococcus in Spain makes more urgent the indication of the vaccine in our community. PMID- 8485281 TI - [Captopril in a single daily dose in arterial hypertension in the elderly. The Badajoz cooperative study. The Badajoz Cooperative Group]. AB - The response to the therapy with captopril administered in one daily dose (between 25 and 100 mg) to a group of 468 old patients with arterial hypertension has been studied. In 87% of the cases, normalization of the arterial pressure was achieved at six months (values lower than 160/95 mmHg). The therapy resulted in a progressive reduction during the follow-up period, with a significant initial reduction (p < 0.001). Just 7.5% of the patients needed the administration of diuretics in addition to the therapy. Just nine patients had to discontinue the follow-up due to side effects (dry cough in 4; gastrointestinal disorders in 4; postural hypertension in 1 case). We conclude that captopril administered in one daily dose is a safe and effective therapy for the treatment of mild to moderate arterial hypertension among the elderly. PMID- 8485282 TI - [Tuberculous liver abscesses as the form of presentation of human immunodeficiency virus infection]. AB - In patients infected by the human immunodeficiency virus (HIV), it has been observed and increase in the incidence of extrapulmonary tuberculosis. Recently, the presence of abdominal tuberculous abscesses has been described as a manifestation of this form of tuberculous disease. However, hepatic abscesses by Mycobacterium tuberculosis are rare among patients infected by the HIV. In the literature, just two patients with this type of abscesses have been described as a form of presentation of the infection by the HIV. In this paper, we present the case of one patient with positive serology to the HIV and two tuberculous abscesses at the hepatic level as part of a disseminated tuberculosis. The main symptoms were fever and lumbar pain. We established the mycobacterial etiology of the abscesses using Ziehl-Neelsen's tinction and culture in Lowenstein's medium of the sample isolated from the abscesses. Abscess drainage under echographic control, in addition to antituberculous chemotherapy, resulted in a quick recovery of the patient, with disappearance of such abscesses as demonstrated by the ultrasonic study performed at three months. PMID- 8485283 TI - [Tracheobronchopathia osteochondroplastica . Apropos a case]. AB - We present one case of osteochondroplastic tracheobronchopathy in a patient with right laterocervical tumoration as a manifestation of a normofunctional nodular goiter detected in a thyroid morphofunctional study, and tracheal stenosis secondary both to the goiter and the tracheobronchial process. The coincidence of these two processes, probably fortuitous, has never been described before. PMID- 8485284 TI - [Imported malaria: 6 cases, 2 of them with an erythrocyte glucose-6-phosphate dehydrogenase deficiency]. AB - We present six cases of imported malaria in Spanish and foreign patients who had visited or lived in areas of malaria endemic. Two patients presented deficit of erythrocytic glucose-6-phosphate dehydrogenase. The main aspects of these two pathologies are analyzed, stressing their similar geographic distribution and the mechanisms by which such deficit protects against the malaria infection. In addition, we describe the problems that may arise with the use of anti-malaria in carriers of this enzymatic deficit; in our patients, the use of chloroquine did not raise any problem. PMID- 8485285 TI - [Systemic mastocytosis. A little-known disease]. PMID- 8485286 TI - [Infection in the cancer patient. The management of neutropenic fever]. PMID- 8485287 TI - [Bearable truth as the crux of information for the cancer patient]. AB - The communication with the patient suffering cancer is attracting an increasing attention. The change of attitudes towards death in our society, the poor training of physicians in this field and other factors have raised this new problem. In addition to the patient and the physician, the relatives and the nursing staff are also involved in the communication process. From the studies already performed, it can be derived that the "bearable truth" has to be supplied to the patient. The application of this concept needs time and dedication to the patient. PMID- 8485288 TI - [Acne conglobata and arthritis]. PMID- 8485289 TI - [Atrial myxoma: its initial manifestations that simulate a systemic disease]. PMID- 8485290 TI - [Ketoconazole and dexamethasone suppression tests]. PMID- 8485291 TI - [Acute cocaine poisoning]. PMID- 8485293 TI - [Marfan's syndrome and thyroid hemiagenesis]. PMID- 8485292 TI - [Pyomyositis of the sternocleidomastoid due to Staphylococcus aureus]. PMID- 8485294 TI - Characterization of beta-turns in cyclic hexapeptides in solution by Fourier transform IR spectroscopy. AB - The beta-turn represents a structural element frequently encountered in globular proteins. However, in spite of various theoretical and experimental studies the ir signature bands of pure beta-turns are still not established beyond doubt. Although considerable information exists now on the ir spectra of alpha-helical and beta-sheet structures, the lack of knowledge concerning turn structures in general, and that of beta-turns in particular, presents a major uncertainty in the estimation of global protein secondary structures from ir spectroscopic data. To obtain more specific information about the characteristic amide bands in beta turns, we report herein an ir spectroscopic analysis of a series of five cyclic pseudo-hexapeptides known to form beta-turns from previous CD and nmr studies [A. Perczel, M. Hollosi, B. M. Foxman, and G. D. Fasman (1991) Journal of the American Chemical Society, Volume 113, pp. 9772-9784]. We show here that in these cyclic peptides the amide groups involved in beta-turns that comprise a ten membered hydrogen-bonded ring (and represent the first H-bond pair in a beta sheet), give rise to characteristic amide I bands in the range 1638-1646 cm-1, with the exact position depending on the solvent and the nature of the side-chain substituents. PMID- 8485296 TI - Approximation and characterization of molecular surfaces. AB - The representation and characterization of molecular surfaces are important in many areas of molecular modeling. Parametric representations of protein molecular surfaces are a compact way to describe a surface, and are useful for the evaluation of surface properties such as the normal vector, principal curvatures, and principal curvature directions. Simplified representations of molecular surfaces are useful for efficient rendering and for the display of large-scale surface features. Several techniques for representing surfaces by expansions of spherical harmonic functions have been reported, but these techniques require that the radius function is single valued, that is, each ray from an origin inside the surface intersects the surface at one and only one point. A new technique is described that removes this limitation and can be used to compute surface shape properties. PMID- 8485295 TI - Peptide design 3(10)-helical conformation of a linear pentapeptide containing two dehydrophenylalanines, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3. AB - alpha,beta-Dehydroamino acids are expected to provide conformational constraint to the peptide backbone. A pentapeptide containing two dehydrophenylalanines (delta ZPhe) separated by one L-amino acid has been synthesized and its solid state conformation determined. The pentapeptide, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3, crystallizes from aqueous methanol in the orthorhombic space group P2(1)2(1)2(1). There are four formula units, C35H46N6O7, in a unit cell of dimensions a = 10.155(3), b = 15.175(1), and c = 23.447(2) A, at room temperature. The structure was solved by direct methods program, SIR88, and refined to a final R = 0.038 based on 3049 reflections with I > 2 sigma (I). All the peptide links are trans and the backbone conformation of the pentapeptide can be described as a 3(10)-helix, with mean phi,psi values of -65.1 degrees and 22.8 degrees (the value is averaged over the first four residues). There are four intramolecular 4-->1 type hydrogen bonds characteristic of 3(10)-type helices. In the crystal, the helices are held together by intermolecular N-H...O = C head-to tail and lateral hydrogen bonding between symmetry related molecules. This mode of packing is similar to the packing motifs observed so often in other oligopeptides that adopt a 3(10)-helical structure. PMID- 8485297 TI - Shape analysis of molecular surfaces. AB - The description of molecular shape is important in the analysis of protein protein and protein-ligand interactions. We describe volumetric and surface-based techniques for computing shape properties of molecular surfaces. The surface is defined as an isocontour of an approximate electron density function. Each technique can compute several scalar and vector surface properties such as the Gaussian and mean curvature, principal curvatures, and principal curvature directions. Shape properties are derived from the eigenvalues and eigenvectors of a 3 by 3 matrix for each surface point. In the volumetric approach, the matrix is the second derivative of an approximate electron density function. In the surface based approach, the matrix is the approximate gradient of the surface normal. Derivatives are computed by convolving the density or the surface normals with the derivatives of a Gaussian function. The variance of the Gaussian determines the effective length scale at which the surface is analyzed. Scalar surface properties are displayed as colored dots or shaded triangles, and vector properties are displayed as line segments from each surface point. This report describes the implementation of these procedures and their use in computing the shape properties of Cu-Zu superoxide dismutase. PMID- 8485298 TI - Photodynamic induction of DNA-protein cross-linking in solution by several sensitizers and visible light. AB - The combined effect of several sensitizers and light on H2O or D2O solutions of DNA-histone complexes, as well as the significance of singlet oxygen (1O2), in this photosensitizing reaction has been studied. On H2O solutions, the production of 1O2, as well as the formation of DNA-protein cross-links (DPCs), were found to be dependent on light dose for all the sensitizers. Mesotetra (4N-methylpyridyl) porphine (T4MPyP), methylene blue (MB), and toluidine blue (TB) were the best photosensitizers with regard to tryptophan photolysis, followed by hematoporphyrin (HP), thioflavine T (TT), and pyronin G (PG). The formation of DPCs showed high initial rates, reaching a plateau at doses over 90 J/cm2. Under these irradiation conditions, the percentage of DPCs induced by the sensitizers decreases in the order T4MPyP > MB > TB >> HP approximately TT >> PG (approximately 0). These DPCs were totally destroyed with proteinase K (15 micrograms/ml). The irradiation of the DNA-histone-sensitizer solutions in the presence of L-carnosine (5 x 10(-4) M) produced approximately a 50% of DPCs inhibition for T4MPyP, MB, and TB, and a total inhibition for HP, TT, and PG. The substitution of H2O by D2O as solvent significantly increased the photodegradation of tryptophan, as well as the photoinduction of DPCs by the sensitizers. The results obtained indicate that singlet oxygen is the main agent responsible in the DNA-protein cross-linking formation. PMID- 8485299 TI - Linear dichroism demonstrates that the bases in poly[d(AC)].poly[d (GT)] and poly[d(AG)].poly[d(CT)] are inclined from perpendicular to the helix axis. AB - Flow linear dichroism is used to measure specific inclinations for each of the four bases in poly[d(AC)].poly[d(GT)] and poly[d(AG)].poly[d(CT)] in both the B and A forms. For the B form in solution the bases are found to have a sizable inclination. Inclination is increased in the A form, as expected. In all cases the pyrimidines are more inclined than the purines. PMID- 8485300 TI - Conformational preference functions for predicting helices in membrane proteins. AB - A suite of FORTRAN programs, PREF, is described for calculating preference functions from the data base of known protein structures and for comparing smoothed profiles of sequence-dependent preferences in proteins of unknown structure. Amino acid preferences for a secondary structure are considered as functions of a sequence environment. Sequence environment of amino acid residue in a protein is defined as an average over some physical, chemical, or statistical property of its primary structure neighbors. The frequency distribution of sequence environments in the data base of soluble protein structures is approximately normal for each amino acid type of known secondary conformation. An analytical expression for the dependence of preferences on sequence environment is obtained after each frequency distribution is replaced by corresponding Gaussian function. The preference for the alpha-helical conformation increases for each amino acid type with the increase of sequence environment of buried solvent-accessible surface areas. We show that a set of preference functions based on buried surface area is useful for predicting folding motifs in alpha-class proteins and in integral membrane proteins. The prediction accuracy for helical residues is 79% for 5 integral membrane proteins and 74% for 11 alpha-class soluble proteins. Most residues found in transmembrane segments of membrane proteins with known alpha-helical structure are predicted to be indeed in the helical conformation because of very high middle helix preferences. Both extramembrane and transmembrane helices in the photosynthetic reaction center M and L subunits are correctly predicted. We point out in the discussion that our method of conformational preference functions can identify what physical properties of the amino acids are important in the formation of particular secondary structure elements. PMID- 8485301 TI - Permethylation alters the conformational transitions and the complexing ability of melittin: a model for methylated proteins. AB - Melittin exhibits a transition from random-coil monomer to helical tetramer as a function of peptide concentration [J. Bello, H. R. Bello, and E. Granados (1982) Biochemistry, Vol. 21, pp. 461-465]. When permethylated on each of the four amino groups (Gly-1 N alpha and Lys-7, 21, and 23 N epsilon) to yield trimethylammonium groups, melittin exists as a random coil and does not show any concentration dependent conformational transition (up to 290 microM). Acylation of the amino groups of melittin with glycine or 5-aminopentanoic acid followed by permethylation increases helix formation, but to a lesser extent than for the unmethylated aminoacylmelittin derivatives. The results are discussed in relation to hydrophobicity, charge repulsions, and ion binding. Melittin, and more weakly, permethylated melittin (MLT-Me) form helical hybrids with an anionic random-coil melittin analogue (E-MLT), in which all the lysine and arginine residues of melittin were replaced by glutamate residues. The hybrid between MLT-Me and E-MLT shows a concentration-dependent increase in helicity. E-MLT, when succinylated at the N-terminal glycine (E-MLT-suc), forms a stronger hybrid with MLT-Me, possibly as a result of increased electrostatic interaction between equal but opposite charges in E-MLT-suc (net charge -6) and MLT-Me (net charge +6). The hybrids exhibit both cold- and heat-induced denaturation, similar to the phenomenon exhibited by proteins. The hybrids also exhibit significant residual structures in the temperature range of 80-100 degrees C, which may be similar to the molten globular states that have been suggested for proteins. PMID- 8485302 TI - Vibrational CD study of the thermal denaturation of poly(rA).poly(rU). AB - The vibrational cd (VCD) of a double-stranded RNA, poly(rA).poly(rU), at pH 7 and moderate added salt concentration (0.1 M) has been measured in both the base stretching and phosphate-stretching regions of the ir as a function of temperature. The data in both cases show two distinct phase transitions. The first is from double- to a triple-stranded form, and the second is from triple- to single-stranded forms, which still retain substantial local order even up to 80 degrees C. The nature of these transitions has been identified by comparison of the VCD and ir absorption spectra of the initially double-stranded samples with those of single-stranded poly(rA) and poly(rU) and with triple-stranded poly (rA).poly-(rU).poly(rU). The large differences in the VCD band shapes allows positive identification of the intermediate and final states. Thus under VCD concentration conditions, a simple helix-to-coil transition can be eliminated for poly(rA).poly(rU) while such a two-step transition can be seen at low salt conditions. All of these observations are consistent with previous studies of the phase transitions of poly(rA).poly(rU) under various salt conditions. Additionally, the VCD is indicative of premelting for all the triple-, double-, and single-strand complexes studied. The triple-strand complex did not show disproportionation to double strand on heating under these added salt conditions. The unusual VCD pattern for low temperature poly(rA).poly(rU), as compared to high G--C content RNAs and DNAs, is qualitatively, but not quantitatively, explained using exciton coupling of localized dipolar transitions in each type of base within the strand. PMID- 8485303 TI - Generation of monoclonal antibodies against HILDA/LIF and their use in the quantitative assay of the cytokine. AB - An adoptive transfer immunization/fusion protocol in mice has been successfully used to raise a series of monoclonal antibodies directed against the Human Interleukin for DA-1a (HILDA)/Leukemia Inhibitory Factor (LIF) cytokine. These antibodies which were raised using recombinant HILDA/LIF purified from conditioned medium of transfected Chinese Hamster Ovary (CHO) cells also react with natural HILDA/LIF from the HSB2 T lymphoma cell line and unglycosylated HILDA/LIF produced in E. coli. They define four separate epitopes, one of which is involved in receptor binding and induction of biological activity. A sensitive sandwich immunoradiometric assay which is linear up to 5 ng/ml HILDA/LIF and can detect as low as 25 pg/ml of the cytokine has been developed. PMID- 8485304 TI - Analysis of enteropathy induced by tumour necrosis factor alpha. AB - Tumour necrosis factor (TNF)-alpha has been implicated in the pathogenesis of experimental and clinical enteropathy, but its exact role is unknown. We show here that a single dose of TNF-alpha causes significant small intestinal pathology in normal adult mice, which develops within 15 minutes, persists for up to 48 hours and is enhanced by interferon-gamma (IFN-gamma). The enteropathy consists of villus atrophy and crypt hyperplasia and is therefore similar to that found in immunologically mediated enteropathies such as graft-versus-host reaction (GvHR). TNF-alpha is also cytotoxic to an intestinal crypt cell line in vitro. Thus, a direct action of TNF-alpha on crypt cells may be involved in its enteropathic effects in vivo. Together, these findings indicate that TNF-alpha alone, or in concert with other cytokines, may be an important effector molecule in immunologically mediated intestinal pathology and may ultimately provide a target for specific immunotherapy for clinical enteropathies. PMID- 8485305 TI - Different regulatory levels are involved in the generation of hemopoietic cytokines (CSFs and IL-6) in fibroblasts stimulated by inflammatory products. AB - In this present study we have characterized the array of hemopoietic cytokines generated by fibroblasts in response to inflammatory signals. It was shown that murine embryo fibroblasts (MEF) are able to generate colony stimulating factors (CSFs) [granulocyte-macrophage (GM-CSF), macrophage-CSF (CSF-1) and granulocyte CSF (G-CSF)] as well as the hemopoietin interleukin 6 (IL-6), while the production of IL-3, IL-4 or tumor necrosis factor (TNF) could not be detected in MEF, as assessed by bioassays or expression of specific mRNA. The production of colony promoting activity was observed when fibroblasts were stimulated by lipopolysaccharide (LPS) or individual cytokines [IL-1, interferon-gamma (IFN gamma), IL-2, IL-4 or TNF] in serum-free conditions as well as by serum itself. These inducers differentially stimulated in MEF the production of various CSFs; LPS induced mainly CSF-1, while cytokines or serum induced equivalent amounts of GM-CSF and CSF-1. The production of IL-6 was induced by LPS in serum-free conditions, while stimulation by cytokines (IL-1 or IFN-gamma) resulted in IL-6 production only in serum-supplemented cultures. Serum by itself did not induce IL 6 production by MEF. The secretion of IL-6 by fibroblasts was detected early and peaked after 6 hours, while CSF activity peaked after 24-72 hours, depending on the inducer. Constitutive mRNA expression of CSF-1 was detected in serum-free conditions in unstimulated MEF, however colony-promoting activity was detected only upon stimulation with cytokines, LPS or serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485306 TI - In-vivo effect of interleukin 3 and erythropoietin, either alone or in combination, on the hematopoietic toxicity associated with zidovudine. AB - We studied the effect of erythropoietin (EPO) and interleukin 3 (IL-3), either alone or in combination, on the hematopoietic toxicity associated with zidovudine in vivo, as determined by peripheral blood indices, and assay of hematopoietic progenitors, i.e. erythroid (CFU-E/BFU-E), myeloid (CFU-GM) and megakaryocyte (CFU-Meg) from bone marrow and spleen. Previous studies from this laboratory have established that dose escalation of zidovudine to normal mice induced a dose dependent decrease in hematocrit, white blood cells and platelets with altered populations of marrow and splenic erythroid, myeloid and megakaryocyte progenitors. Daily administration of EPO (50 U/animal, i.p.) and/or IL-3 (5 U/animal, i.p.) was associated with altered peripheral blood indices and progenitor cells. In general, use of EPO and IL-3 alone reduced zidovudine induced toxicity, notably in erythropoiesis; however, combination EPO/IL-3 was associated with enhanced toxicity with an observed rebound only with the use of < 2.5 mg/ml drug; 2.5 mg/ml drug in the presence of combination EPO/IL-3 accelerated zidovudine-erythroid toxicity. A similar response was noted with circulating platelets and megakaryocyte progenitors. Use of EPO or IL-3, either alone or in combination, failed to reverse zidovudine-induced neutropenia. These studies demonstrate that use of EPO or IL-3, either alone or in combination may serve as an effective adjuvant therapy to modulate the erythroid toxicity associated with lower doses of zidovudine; however, this cytokine therapy was ineffective modulating zidovudine-induced myelosuppression when used in vivo. A reversal in zidovudine-induced myeloid toxicity, therefore may require the use of a myelopoiesis inducing cytokine. PMID- 8485307 TI - High-affinity IgG autoantibodies to IL-6 in sera of normal individuals are competitive inhibitors of IL-6 in vitro. AB - Nano- to picomolar concentrations of high affinity IgG antibody to interleukin 6 (IL-6ab) were detected in sera of 71 of 467 normal Danish blood donors (15%). IL 6 bound to the Fab fragments of IL-6ab, and the antibody specifically and competitively interfered with enzyme-linked immunosorbent assays for human IL-6. Only IL-6ab-positive sera interfered with these ELISAs. A statistically positive correlation was found between total IL-6 binding and specific IL-6 binding to serum (P < 0.0001), suggesting that IL-6ab dominates as IL-6 binding factors in normal human serum. The IL-6ab also inhibited binding of IL-6 to receptors on the human U-937 macrophage-like cell line, the human U-266 myeloma cell line and the mouse hybridoma cell line B13.29, clone B9 (B9 cells). IL-6-induced proliferation of the B9 cells was competitively inhibited by IL-6ab. We conclude that sera of normal individuals may contain appreciable levels of autoantibodies to IL-6. These IgG autoantibodies may be physiologically and pathophysiologically important because they are potent inhibitors of IL-6 in vitro. PMID- 8485308 TI - Expression of functional beta-platelet-derived growth factor receptors on hematopoietic cell lines. AB - The beta-type receptor of platelet-derived growth factor (beta PDGFR) is a class III transmembrane receptor with tyrosine kinase activity. The beta PDGFR gene is located on mouse chromosome 18 close to the c-fms gene which codes for the colony stimulating factor-1 receptor (CSF-1R). We previously reported that in a high percentage of myeloblastic leukemias induced by the Friend helper murine leukemia virus (F-MuLV), proviruses were integrated in the first intron of the c-fms gene leading to an enhanced expression of c-fms mRNA. Since activation by proviral insertion can act at long distance, we studied beta PDGF receptor gene expression in murine myeloblastic leukemias. This gene was found to be frequently expressed but the level of beta PDGF receptor mRNA was weak and not related to proviral activation. High affinity binding sites were expressed on myeloblastic cells and ligand binding induced cell proliferation. To determine whether beta PDGFR expression is a common feature in hematopoietic cells, we tested cell lines belonging to other hematopoietic lineages. We found that multipotent stem and mast cell lines also expressed the beta PDGF receptor gene. This suggests that PDGF, known as a mitogen for connective tissue cells, could also play a role in normal hematopoiesis. PMID- 8485309 TI - Reliability of fine needle aspiration cytology for distinguishing between carcinoma, lymphoma and sarcoma; the influence of clinical information. AB - To investigate interobserver variation of fine needle aspiration (FNA) cytological diagnosis with respect to distinguishing between carcinoma, sarcoma and lymphoma, a set of 80 randomly sampled slides was randomized twice and read 'blindly' by five cytopathologists. In the first round the slides were read without any information, and in the second round clinical information was provided. Histology was used as a reference standard. In the first round, the positive predictive values for the cytological diagnosis of carcinoma, sarcoma and lymphoma were 93%, 94% and 86% respectively. In the second round the positive predictive values for the cytological diagnoses of carcinoma, sarcoma and lymphoma were 95%, 99% and 99%, respectively. Interobserver variability, tested with weighted kappa scores (range 0.73-0.92) between histological and cytological diagnosis, was low. The most accurate FNA cytologic classification was obtained when the clinical context was known. PMID- 8485310 TI - Bladder involvement in disseminated malignant lymphoma diagnosed by voided urine cytology. PMID- 8485311 TI - Intraocular lymphoma--a case report. PMID- 8485312 TI - Disseminated strongyloidiasis: a case report. PMID- 8485313 TI - Some aspects of cervical screening in southern New Zealand; the situation before implementation of the national cervical cancer prevention programme. AB - To gain some idea of cervical screening in Otago and Southland (two southern provinces of New Zealand), before the implementation of a national cervical cancer prevention programme, a questionnaire was sent to all doctors identified as smear takers. Questionnaires were returned by 75% of the doctors. Only 53.8% of practice nurses were involved in taking smears. Well Women Clinics staffed by nurses were not widespread in either province. Just under half (46.4%) of doctors took cervical smears as part of a health check programme. Sixty-three per cent (63.3%) routinely performed a pelvic examination when taking a smear. Surprisingly few doctors were familiar with the technique of placing spatula and cytobrush samples on one slide, a manoeuvre which could significantly reduce the workload of the cytology laboratories. Only a minority of doctors were aware of a new sampler which can provide samples equivalent to combined spatular-cytobrush smears. There was confusion over the timing of a repeat smear following two normal ones. The recommended interval of 3 years was only complied with by 44.2% of doctors. However, 71.4% of respondents did remind women to have smears. The study indicates that many doctors already provide patients with a good cervical screening service, and this augers well for the national screening programme. PMID- 8485314 TI - The effect of filtration on the cellular components in bronchoalveolar lavage fluid. AB - The effect of filtration through two layers of cotton gauze on the cellular composition of bronchoalveolar lavage (BAL) fluid was studied in 25 patients with pulmonary disease. There was no significant difference between median total cell count in unfiltered and filtered BAL (P = 0.73) or in the distribution of neutrophils or eosinophils. The percentage of bronchial epithelial cells was significantly higher in unfiltered than in filtered BAL (P = 0.02). Furthermore, differential cell counts showed a significantly lower percentage of alveolar macrophages (P = 0.04), and a significantly higher percentage of lymphocytes (P = 0.04) in unfiltered compared with filtered BAL. Thus, gauze filtration results in a loss of bronchial epithelial cells and lymphocytes, and is not recommended in the routine analysis of cellular components in BAL fluid. PMID- 8485315 TI - Expression of vimentin and epidermal growth factor receptor in effusions from patients with breast cancer; correlation with oestrogen and progesterone receptor status. AB - The epidermal growth factor receptor (EGFr) status and the vimentin (V) status of malignant cells in pleural fluids from patients with breast cancer were determined using an immunoperoxidase labelling technique. The results were correlated with the oestrogen receptor (ER) and the progesterone receptor (PR) status of the primary tumour and with disease-free survival time of the patient. A negative correlation between EGFr and V status and hormone receptor status was found. The longest mean survival time occurred in patients with negative EGFr and V status and positive hormone receptor (ER and PR) status. The shortest mean survival time occurred in patients with positive EGFr and V and negative ER and PR status. PMID- 8485316 TI - Fine needle aspiration cytology of myxoid liposarcoma; a study of 18 tumours. AB - The cytological features of 18 myxoid liposarcomas from 12 patients were analysed. The most consistent cytological features were: abundant myxoid matrix, several small tissue fragments with uniform small, round or stellate cells and a network of branching thin-walled capillaries. The presence of univacoulated or multivacuolated lipoblasts was noted frequently, but not in all aspirates. The diagnostic importance of vacuolated lipoblasts and the main problems of differential cytodiagnosis are discussed. PMID- 8485317 TI - A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization. AB - The fission yeast dsk1+ gene, a multicopy suppressor for cold-sensitive dis1 mutants, encodes a novel 61-kd protein kinase. It is a phosphoprotein, and phosphoserine is the major phosphorylated amino acid. Hyperphosphorylation of dsk1 causes a mobility shift, resulting in two dsk1-specific protein bands. The phosphorylation pattern is strikingly altered when cell cycle progression is delayed or arrested. The slowly migrating phosphorylated form is prominent in mitotically arrested cells, and the fast migrating form is enriched in interphase arrested cells. dsk1 is a protein kinase. It auto-phosphorylates as well as phosphorylates myelin basic protein (MBP). Phosphotyrosine as well as phosphoserine/threonine were found in autophosphorylation, but no tyrosine phosphorylation occurs when MBP was used as the substrate. The dsk1 immunoprecipitates from mitotically arrested cells have a several-fold higher kinase activity than that from wild type. The haploid gene disruptant is viable, indicating that the dsk1+ gene is non-essential for viability. High dosage of dsk1+, however, strongly delays the G2/M progression. Immunofluorescence microscopy using anti-dsk1 antibody shows that localization pattern of dsk1 protein strikingly alters depending on cell cycle stages. In G2-arrested cells, dsk1 locates in the cytoplasm, whereas in mitotically arrested cells, nuclear stain is intense. In wild-type cells, nuclear stain is seen only in mitotic cells. Hence dsk1 protein may play an important role in mitotic control by altering cellular location, degree of phosphorylation and kinase activity. We discuss possible roles of dsk1 kinase as an add-on regulator in mitosis. PMID- 8485318 TI - Requirement for diacylglycerol and protein kinase C in HeLa cell-substratum adhesion and their feedback amplification of arachidonic acid production for optimum cell spreading. AB - Release of arachidonic acid (AA) and subsequent formation of a lipoxygenase (LOX) metabolite(s) is an obligatory signal to induce spreading of HeLa cells on a gelatin substratum (Chun and Jacobson, 1992). This study characterizes signaling pathways that follow the LOX metabolite(s) formation. Levels of diacylglycerol (DG) increase upon attachment and before cell spreading on a gelatin substratum. DG production and cell spreading are insignificant when phospholipase A2 (PLA2) or LOX is blocked. In contrast, when cells in suspension where PLA2 activity is not stimulated are treated with exogenous AA, DG production is turned on, and inhibition of LOX turns it off. This indicates that the formation of a LOX metabolite(s) from AA released during cell attachment induces the production of DG. Consistent with the DG production is the activation of protein kinase C (PKC) which, as with AA and DG, occurs upon attachment and before cell spreading. Inhibition of AA release and subsequent DG production blocks both PKC activation and cell spreading. Cell spreading is also blocked by the inhibition of PKC with calphostin C or sphingosine. The inhibition of cell spreading induced by blocking AA release is reversed by the direct activation of PKC with phorbol ester. However, the inhibition of cell spreading induced by PKC inhibition is not reversed by exogenously applied AA. In addition, inhibition of PKC does not block AA release and DG production. The data indicate that there is a sequence of events triggered by HeLa cell attachment to a gelatin substratum that leads to the initiation of cell spreading: AA release, a LOX metabolite(s) formation, DG production, and PKC activation. The data also provide evidence indicating that HeLa cell spreading is a cyclic feedback amplification process centered on the production of AA, which is the first messenger produced in the sequence of messengers initiating cell spreading. Both DG and PKC activity that are increased during HeLa cell attachment to a gelatin substratum appear to be involved. DG not only activates PKC, which is essential for cell spreading, but is also hydrolyzed to AA. PKC, which is initially activated as consequence of AA production, also increases more AA production by activating PLA2. PMID- 8485319 TI - The surface cyclic AMP receptors, cAR1, cAR2, and cAR3, promote Ca2+ influx in Dictyostelium discoideum by a G alpha 2-independent mechanism. AB - Activation of surface folate receptors or cyclic AMP (cAMP) receptor (cAR) 1 in Dictyostelium triggers within 5-10 s an influx of extracellular Ca2+ that continues for 20 s. To further characterize the receptor-mediated Ca2+ entry, we analyzed 45Ca2+ uptake in amoebas overexpressing cAR2 or cAR3, cARs present during multicellular development. Both receptors induced a cAMP-dependent Ca2+ uptake that had comparable kinetics, ion selectivity, and inhibitor profiles as folate- and cAR1-mediated Ca2+ uptake. Analysis of mutants indicated that receptor-induced Ca2+ entry does not require G protein alpha subunits G alpha 1, G alpha 2, G alpha 3, G alpha 4, G alpha 7, or G alpha 8. Overexpression of cAR1 or cAR3 in g alpha 2- cells did not restore certain G alpha 2-dependent events, such as aggregation, or cAMP-mediated activation of adenylate and guanylate cyclases, but these strains displayed a cAMP-mediated Ca2+ influx with kinetics comparable to wild-type aggregation-competent cells. These results suggest that a plasma membrane-associated Ca(2+)-influx system may be activated by at least four distinct chemoreceptors during Dictyostelium development and that the response may be independent of G proteins. PMID- 8485320 TI - Intracellular free Ca2+ in the cell cycle in human fibroblasts: transitions between G1 and G0 and progression into S phase. AB - Intracellular free calcium ([Ca2+]i) has been proposed to play an important part in the regulation of the cell cycle. Although a number of studies have shown that stimulation of quiescent cells with growth factors causes an immediate rise in [Ca2+]i (Rabinovitch et al., 1986; Vincentini and Villereal, 1986; Hesketh et al., 1988; Tucker et al., 1989, Wahl et al., 1990), a causal relationship between the [Ca2+]i transient and the ability of the cells to reenter the cell cycle has not been firmly established. We have found that blocking the mitogen-induced elevation of [Ca2+]i with the cytoplasmic [Ca2+]i buffer dimethyl BAPTA (dmBAPTA) also blocks subsequent entry of cells into S phase. The dose response curves for inhibition of serum stimulation of [Ca2+]i and DNA synthesis by dmBAPTA are virtually identical including an anomalous stimulation observed at low levels of dmBAPTA. Reversal of the [Ca2+]i buffering effect of dmBAPTA by transient exposure of the cells to the Ca2+ ionophore ionomycin also reverses the inhibition of DNA synthesis 20-24 h later. Ionomycin by itself does not stimulate DNA synthesis. These data are consistent with the conclusion that a transient increase in [Ca2+]i occurring shortly after serum stimulation of quiescent fibroblasts is necessary but not sufficient for subsequent entry of the cells into S phase. This study is the first to show a direct relationship between early serum stimulated Cai2+ increase and subsequent DNA synthesis in human cells. It also goes beyond recent studies on BALB/3T3 cells by providing dose response data and demonstrating reversibility, which are strong indications of a cause and effect relationship. PMID- 8485322 TI - Biochemical and cellular basis for potential therapeutic value of n-3 fatty acids derived from fish oil. PMID- 8485321 TI - Dynamics of microtubules from erythrocyte marginal bands. AB - Microtubules can adjust their length by the mechanism of dynamic instability, that is by switching between phases of growth and shrinkage. Thus far this phenomenon has been studied with microtubules that contain several components, that is, a mixture of tubulin isoforms, with or without a mixture of microtubule associated proteins (MAPs), which can act as regulators of dynamic instability. Here we concentrate on the influence of the tubulin component. We have studied MAP-free microtubules from the marginal band of avian erythrocytes and compared them with mammalian brain microtubules. The erythrocyte system was selected because it represents a naturally stable aggregate of microtubules; second, the tubulin is largely homogeneous, in contrast to brain tubulin. Qualitatively, erythrocyte microtubules show similar features as brain microtubules, but they were found to be much less dynamic. The critical concentration of elongation, and the rates of association and dissociation of tubulin are all lower than with brain microtubules. Catastrophes are rare, rescues frequent, and shrinkage slow. This means that dynamic instability can be controlled by the tubulin isotype, independently of MAPs. Moreover, the extent of dynamic behavior is highly dependent on buffer conditions. In particular, dynamic instability is strongly enhanced in phosphate buffer, both for erythrocyte marginal band and brain microtubules. The lower stability in phosphate buffer argues against the hypothesis that a cap of tubulin.GDP.Pi subunits stabilizes microtubules. The difference in dynamics between tubulin isotypes and between the two ends of microtubules is preserved in the different buffer systems. PMID- 8485323 TI - Long-term parenteral nutrition in cystic fibrosis. AB - The effects of parenteral nutrition (PN) with high lipid content were studied in 18 cystic fibrosis patients in this pilot investigation. The patients were randomly assigned to one of two groups. During the first 4-mo period, group 1 received PN and group 2 received routine therapy. During the second 4-mo period, PN was discontinued in group 1 and instituted in group 2. When the effect of PN was considered for both treatment groups, its general effect was to increase body fat content with little or no impact on respiratory function, exercise tolerance, or recurrent infections. However, subsequent analysis and clinical observation suggested that patients receiving PN responded in two seemingly distinct patterns: some demonstrated apparent clinical improvement and benefit, and others did not. A positive response in pulmonary and exercise function was closely correlated to a rise in serum dihomo-gamma-linolenic acid (DHLA) concentrations during PN. Pulmonary function improved in patients who normalized their DHLA levels (vital capacity increased from 2.2 +/- 0.3 to 2.6 +/- 0.3 area %, p < 0.05), whereas those who continued to have undetectable levels of DHLA deteriorated (forced expiratory volume in 1 s decreased from 0.7 +/- to 0.6 +/- 0.1, p < 0.001). PN applied to malnourished patients with cystic fibrosis results in beneficial effects in a subgroup characterized by the presence of DHLA in serum; for the group as a whole, the positive effects are minimal. PMID- 8485324 TI - Patterns of energy expenditure in intensive-care patients. AB - We studied the changes in energy expenditure (EE) in response to multiple injury (n = 6), subarachnoidal hemorrhage (n = 8), low-cardiac-output syndrome after open-heart surgery (n = 6), and uncomplicated coronary artery surgery (n = 10). Measurements were made during 5 consecutive days. In the multiple injury group, EE was 30% higher than predicted basal EE (range 10-52%) within 27 h after trauma, and this hypermetabolism remained unchanged throughout the study. After subarachnoidal hemorrhage, EE was 18% higher than predicted (range 0-45%) and the operation caused only a minor further increment in EE. Also, these patients remained hypermetabolic throughout the study. In the low-cardiac-output syndrome group, the increase in EE was less prominent (mean 15%, range 0-34%), but the pattern of hypermetabolism was similar to that observed in the multiple injury and subarachnoidal hemorrhage groups. The metabolic response to uncomplicated coronary artery surgery resembled the response to general surgery. We conclude that 1) there is an early consistent increase in EE in various groups of surgical intensive-care patients; 2) with appropriate treatment of the circulation, a prompt hypermetabolic response to surgical trauma is maintained even during low cardiac-output syndrome; and 3) the marked hypermetabolism after subarachnoidal hemorrhage at the central nervous system is an integral part of the hypermetabolic response to injury. PMID- 8485325 TI - Distal splenorenal shunt and insulin secretion, plasma glucagon, and glucose homeostasis in cirrhosis. AB - Over the 1st postoperative yr, distal splenorenal shunt (DSRS) in cirrhotic patients is followed by a reduction in portal perfusion resulting from a spontaneous opening of portal-systemic collaterals. This can influence plasma levels of insulin and glucagon. Fasting plasma glucose, insulin, C-peptide, and glucagon and their 5-h responses to a protein meal (which directly stimulates the hormone secretions) were measured before and 3 and 12 mo after DSRS in 10 cirrhotic patients. Hormone effectiveness and pancreatic alpha- and beta-cell sensitivities to ammonia (NH3), amino acids, and glucose were also calculated. Liver function and portal vein diameter were assessed before each study. Seven cirrhotic patients treated with injection sclerotherapy of esophageal varices served as a control group. Liver function did not deteriorate in either patient group. An increase in fasting glucagon (from 181 +/- 22 to 242 +/- 22 and 255 +/- 22 pg/ml, p = 0.02) and NH3 (from 57 +/- 8 to 84 +/- 11 and 97 +/- 14 micrograms/dl, p = 0.04) and a decrease in glucagon effectiveness (from 0.56 +/- 0.06 to 0.39 +/- 0.05 and 0.035 +/- 0.03, p = 0.047) and portal vein diameter (from 16.0 +/- 1.1 to 11.3 +/- 0.8 and 9.4 +/- 0.6 mm, p < 0.001) was found only in DSRS patients. The elevation in glucagon was correlated with that of NH3 at 3 mo (r = 0.83, p = 0.003) and with the reduction of portal vein diameter at 1 yr (r = -0.81, p = 0.005). In cirrhosis, DSRS does not influence insulin secretion or its plasma level and effectiveness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485326 TI - Effect of nutrition status and other factors on length of hospital stay after major gastrointestinal surgery. AB - Various factors may prolong postoperative recovery and the length of stay (LOS) in the hospital. In a retrospective study of 245 adult patients who had no oral intake for 5 days after major gastrointestinal surgery, we used a correlation matrix to describe the population and determine the effects of the following factors on LOS: malnutrition, complication status, stress level, type of surgery, pathology, period of inadequate nutrient intake, and use of nutritional support. LOS was markedly prolonged in malnourished patients compared with those who were not (23.5 +/- 16.5 vs. 16.5 +/- 10.7 days, means +/- SD, p < 0.001). Patients were then grouped into those who had nutritional support and those who had not, and a nutrition classification was derived by examining the uncertainty (entropy) in the data matrix that allowed separation of the population into distinct groups. Nutrition and complication status and days without oral nutrient intake were discriminative. Analysis of variance and multivariate studies were also used to determine whether the presence of malnutrition, complications, both together, or neither could predict LOS and to determine the confounding effect of nutritional support on LOS. A significantly extended LOS persisted for patients with malnutrition or complications and was most prolonged for those with both, but patients who received nutritional support had a greater LOS than those who did not. In addition to the effects of nutritional support, malnutrition, and complication status, LOS correlated with the duration of the postoperative period without oral nutrient intake. We therefore recommend systematic and early nutritional intervention for selected gastrointestinal surgical patients. PMID- 8485327 TI - Leucine and manifestation of antitumor activity by valine-depleted amino acid imbalance. AB - With a commercially available balanced 10% amino acid solution as control (I), imbalance solutions were prepared by the removal of valine (II), valine and leucine (III), valine and isoleucine (IV), and valine, leucine, and isoleucine (V). The solutions, in combination with total parenteral nutrition, were given to rats with AH-109A hepatoma for 7 consecutive days to evaluate antitumor activity. Although there were no significant differences in carcass weight after treatment among groups I-IV, a decrease was noted in group V. Tumor weights in groups II-V, relative to that in group I, were 39, 57, 43, and 44%, respectively. Antitumor activity was thus noted in all imbalance groups, although activity in group III was lower than that in group II. These results indicate that the concurrent depletion of leucine and/or isoleucine along with valine is undesirable because of lower antitumor activity and an adverse effect on host development. Leucine is thus suggested to play an important role in augmenting the activity of valine depleted imbalance. PMID- 8485328 TI - Alteration of pulmonary function by filtration of intravenous nutrient mixture. AB - In view of contradicting results concerning alteration in lung function during hyperalimentation and the administration of intravenous lipid emulsion, a study was planned to determine possible changes in pulmonary blood perfusion during administration of total nutrient admixture (TNA) and the effect of filtration. Sixteen patients (8 men, 8 women; mean age 65.6 yr) with no previous lung disease received TNA at the rate of 4-5 g lipid/h as preoperative treatment for 5-9 days (mean 6.7 days). The 5-microns filter was randomly used in eight patients. The lung blood perfusion parameters measured repeatedly during this period included blood gases, percentage of the predicted value of vital capacity (VC), and pulmonary diffusing capacity for carbon monoxide (DLCO), as well as the value of the dead space volume and the tidal volume ratio (VD/VT) and the calculated shunt (QS/QT). TNA infusion appears to cause only a slight decrease in PaO2 and DLCO and a similar increase in VC and QS/QT, whereas VD/VT decreased significantly. The latter effect was abolished by filtration of TNA. There were no significant differences between the two groups. We therefore conclude that short-term preoperative administration of TNA at the rate of 4-5 g lipid/h in patients without preexisting lung disease does not jeopardize lung functions. Filtration of the TNA is, however, recommended to avoid the potential hazardous effects of long-term treatment of TNA on lung function. PMID- 8485329 TI - Stillbirth rates and folic acid and zinc status in low-socioeconomic pregnant women of Brazilian Amazon. AB - Twenty-five women in their first trimester and 25 women in their third trimester of pregnancy were randomly chosen from the slum areas of eight towns in the Brazilian Amazon (Manaus, Sao Luis, Boa Vista, Porto Velho, Sao Gabriel, Santarem, Tefe, and Benjamin Constant). Blood samples were removed from the subjects for folic acid and zinc analyses, and the women were asked questions about whether they had suffered from complications during previous pregnancies. It was found that the stillbirth rates reported ranged from 0 to 20/1000 pregnancies. The town that had the highest stillbirth rate (Santarem) also had the highest percentage of women with deficient erythrocyte (red blood cell, RBC) folate status. All of the women in Santarem also had deficient serum folate levels in both trimesters of pregnancy, as well as the lowest average RBC folate value in the third trimester of pregnancy. The same town was also one of two in which the pregnant women had the lowest mean serum zinc levels in the third trimester. PMID- 8485330 TI - Acute tetany in the Crohn's patient with osteomalacia. PMID- 8485331 TI - Carbohydrate metabolism and requirements for nutritional support: Part II. PMID- 8485332 TI - Calorie-restricted weight reduction, blood pressure, and atrial natriuretic peptides. AB - Calorie restriction with resultant weight loss lowers arterial blood pressure in obese people. The mechanism of this blood-pressure reduction has been unknown, but recent evidence suggests that the atrial natriuretic peptide hormonal system may play a role in the blood-pressure changes associated with calorie-reduction induced weight loss. This newly described hormonal system consists of a 126-amino acid (aa) prohormone synthesized primarily in the heart with a 98-aa NH2-terminal and a 28-aa COOH-terminal of this prohormone released into the circulation. Four peptides consisting of aa 1-30, 31-67, 79-98, and 99-126 of this prohormone each have blood-pressure-lowering properties. The circulating concentrations of these peptides increase in people with high blood pressure in an apparent attempt to overcome the constriction of blood vessels. With calorie-induced weight reduction, the elevated levels of these peptides decrease and correlate in a linear fashion (p < 0.001) with blood-pressure reduction. During this blood pressure reduction, plasma aldosterone and plasma renin activity inversely correlate with the concentration of atrial natriuretic peptides and blood pressure. This observation is consistent with the ability of atrial natriuretic factor (i.e., aa 99-126 of the prohormone) to inhibit renin release and aldosterone secretion from the adrenal gland. The atrial natriuretic peptide hormonal system appears to be important in blood-pressure regulation in people who are at their ideal body weight and in those who are overweight. PMID- 8485333 TI - Oxygen consumption in critical illness. PMID- 8485334 TI - Do carbohydrates make you fat? PMID- 8485336 TI - New food labeling addresses major health concerns. PMID- 8485335 TI - Hypothesis tests. PMID- 8485337 TI - Ischemic heart disease and dietary copper--towards a unifying hypothesis. PMID- 8485338 TI - Routine sensitive peptide mapping using LC/MS of therapeutic proteins produced by recombinant DNA technology. AB - At the Sixth International Conference on Methods in Protein Sequence Analysis held in Seattle, Washington, August 17-21, 1986, Frank Robey of the Food and Drug Administration (FDA) proposed a "wish list" of possible future techniques for the analysis of recombinant products. Included in this list was liquid chromatography (HPLC) in-line with mass spectrometry for peptide mapping. This wish has come true. In 1988, a new technique, electrospray ionization (ESI) of liquids with quadrupole mass analysis, became a major breakthrough in accurately measuring molecular weights of proteins up to 100,000 daltons or more. Now, using an affordable, simple, easy-to-use single-stage quadrupole mass spectrometer, peptide mapping is routine. PMID- 8485339 TI - Solution synthesis of mu-conotoxin GIIIB: optimization of the oxidative folding reaction. AB - mu-Conotoxin GIIIB, a skeletal muscle sodium channel specific blocker, was synthesized by the solution procedure. The whole molecule, which is composed of 22 amino acid residues including six cysteinyl and three trans-4-hydroxy-L-prolyl residues, was constructed from three segments. After removal of all protecting groups, the hexa-SH peptide was subjected to an oxidative folding reaction at a peptide concentration of 1 x 10(-5) M. Three major products 1, 2 and 3 were formed in a ratio of 1:4:3. Determination of the disulfide structures in each product revealed them to be disulfide isomers, with similar connectivities in the latter two. Study of the biological activities of the three products in mice indicated that only product 1, which is a minor component, has the same potency as the natural product. Analysis of the folding process at a peptide concentration of 1 x 10(-5) M showed that the disulfide bond between Cys10 and Cys15 was initially formed, thus leading to the predominant generation of products 2 and 3. The optimal conditions for the formation of product 1 (mu conotoxin GIIIB) were obtained by increasing the peptide concentration in the oxidation reaction mixture or by using redox reagents, both of which functioned as promoters for the thiol-disulfide exchange reaction of the mismatched disulfide bond between Cys10 and Cys15. PMID- 8485340 TI - Peptide-based assay for the identification of endothelin-converting enzyme inhibitors. AB - A simple, solid-phase assay usable for the detection of endothelin-converting enzyme activity and inhibitors has been developed. It uses a multimeric peptide immobilized on microtiter plates that is able to specifically recognize the Big Endothelin fragment 16-32 derivatized with biotin. This fragment is cleaved between residues 21-22 by alpha-chymotrypsin with almost the same proteolysis rate as Big Endothelin, and after enzyme treatment it does not bind to the multimeric peptide adsorbed on the microtiter plates. The amount of uncleaved peptide bound to the plate is detected by subsequent treatment with streptavidin conjugated to peroxidase, followed by a chromogenic reaction. Model inhibitor profiles generated for alpha-chymotrypsin, a protease known to convert Big Endothelin in endothelin, demonstrated the utility of this assay as a rapid high throughput aid in the study of Big Endothelin enzymatic processing and possibly in the identification of putative enzyme inhibitors. PMID- 8485341 TI - Comparative multiple synthesis of fifty linear peptides: evaluation of cotton carrier vs. T bag-benzhydrylamine resin. AB - Parallel simultaneous synthesis of fifty linear peptides has been carried out in order to compare in detail two promising methodologies of simultaneous multiple peptide synthesis (SMPS): the "T bag" method, utilizing 4-methyl-benzhydrylamine resin (MeBHA), and synthesis on derivatized Fmoc-Gly-O-cotton fabric strips. The basic set of experiments, which utilizes identical Fmoc/Bu(t) strategy for both approaches, shows that the peptides synthesized on cotton are superior in purity to those synthesized using T bags. In experiments utilizing Boc/Bzl strategy in T bags, the purities of peptides were higher than in the case of peptides synthesized in T bags by Fmoc/Bu(t) strategy, and comparable with the purities achieved in synthesis performed on cotton. The lower yields on cotton are caused by mechanical losses in the given experimental arrangement. PMID- 8485342 TI - Investigation of cyclic depsipeptides by fast atom bombardment-mass spectrometry. AB - In recent years, the synthetic analogue elcatonin has been used successfully in the treatment of osteoporosis. During an investigation of synthetic strategies for the production of elcatonin, a number of peptide products were generated. These could be purified by liquid chromatography and were shown to have identical amino acid compositions. Investigation by fast atom bombardment-mass spectrometry revealed three of the peptides to have a common pseudomolecular ion but notably dissimilar fragmentation patterns. Further studies involving chemical modification, mass spectrometry and chromatographic separation showed these products to be novel depsipeptides, cyclized with an ester bond between either the serine or the threonine residue and the side chain of aminosuberic acid. PMID- 8485343 TI - Ethical awareness, understanding and collaboration. PMID- 8485344 TI - Haemodynamic profiles and the critical care nurse. AB - The last decade has witnessed phenomenal developments available for the critically ill, especially for the patient in shock. These advances have implications for all members of the health care team as new roles and functions are constantly emerging. As the therapies practised today continue to expand, this demands a greater level of expertise for all those involved in critical care. This ever-increasing complexity mandates that we examine the future direction of critical care nursing. This paper examines one area of clinical development--the haemodynamic profile. From a theoretical knowledge base on shock with a review of patient goals of therapy, the discussion is developed with reference to the clinical application of the haemodynamic profile. The parameters, their calculation and meaning for patient treatment is examined using clinical exemplars. The paper concludes by re-affirming the themes drawn on throughout the paper of holistic care, independent and interdependent team relationships and accountable professional practice. PMID- 8485346 TI - Breaking the news: informing visitors that a patient has died. AB - Most nurses working in critical care areas for any length of time will be involved in informing visitors that a patient has died. This paper describes some of the methods which may be used to give this news and some of the means of providing support to visitors at this time. PMID- 8485345 TI - Ventricular assist devices for the failing heart: a nursing focus. AB - The last decade has witnessed phenomenal advances in the therapies available for critically ill patients, especially for those patients in circulatory failure. This paper presents an overview of mechanical assist devices, focusing on the use of ventricular assist for the failing heart. From a basic review of cardiac failure, the principles of ventricular assist and the indications for its use are examined. After reviewing the ventricular assist devices currently available, the discussion moves to the expert nursing skills required by a patient receiving ventricular assist therapy. All aspects of clinical practice are discussed, with particular emphasis on the full use of assessment skills in order to facilitate care planning and ensure safe delivery of care. These expert nursing skills are considered within the framework of collaborative care. Patients needing ventricular assist may require some of the most advanced holistic nursing skills that critical care nurses possess. PMID- 8485347 TI - Monoclonal antibodies--the future of pharmacology. PMID- 8485348 TI - The needs of a patient in severe status asthmaticus: experiences of a nurse patient in an intensive care unit. AB - Biopsychosocial being is now accepted in nursing as a term which can be used to describe any human being. This is an account of what it means, illustrated in the life of one person. Pilar Arcas Ruiz is a Spanish nurse who left medical education to train as a nurse, but later completed the requirements for medical qualification in order to use it when necessary to advance nursing in Spain. PMID- 8485350 TI - Performing endotracheal suction on children: a literature review and implications for nursing practice. AB - The purpose in this paper is to review the literature concerning endotracheal tube suction as a nursing procedure used for children, and to discuss common techniques and problems. From the discussion, recommendations for care are extrapolated in order to minimise discomfort for, and risks to, the patients. PMID- 8485349 TI - The communication process with ventilator patients in the ICU as perceived by the nursing staff. AB - Intensive care unit (ICU) nurses (n = 27) were interviewed about their experiences and opinions of the communication process with ventilator treated patients. Nurses with limited ICU experience considered the initial contact with a new critically ill ventilated patient more frustrating than experienced nurses. The nurses thought that the content of the communication commonly requested by a patient was dominated by factors related to the clinical condition, prognosis and reassurance that the situation was under control. Factors considered to limit the communication and to create feelings of uncertainty and stress for nurses with an ICU experience of less than 5 years were: work overload, unstable condition of the patient, impaired communication with the patient, and their own personal problems or worries. For nurses with an ICU experience of more than 5 years stress was more commonly evoked by the presence of worried and anxious spouses/relatives, and by the feeling that something was wrong with the patient but they were unable to identify the problem. Failure to understand a ventilated patient could induce feelings of incompetence, stress and sometimes even despair. The present small scale study shows that there are many factors, in addition to ICU experience, that may influence the ability of an ICU nurse to establish and maintain a well functioning communication with ventilated patients and the likelihood of doing so. PMID- 8485351 TI - Empathy and technology in the coronary care unit. AB - This paper explores the emergence of nursing in the mid 19th century as a 'caring' or 'curing' occupation. Nursing evolved as the discipline of caring whilst cure was the doctor's domain. Important though caring was, it was perceived as women's work and therefore of low status and considerably less powerful than the male dominated curing role. The definitions and practice of caring have changed since the Victorian era, but it continues to be perceived by many as secondary to medicine's curing role. The paper explores this issue in the speciality of coronary care nursing and also whether coronary care nursing is more 'cure' than 'care' orientated. Coronary care nursing began as a technological and physical speciality--more 'cure'-orientated than 'care' orientated and this has led to the specialty being especially attractive to male nurses. However, since the purpose of CCU began as the prevention of death, and the possibility of death is an inescapable part of the nurses' work, the ability to be empathic is essential. The paper concludes that coronary care nursing appears to contain both 'curing' elements (technological/physical) and 'caring' elements (empathy), both of which are practised by many coronary care nurses. The 'cure' elements of physical observation, treatment and technological maintenance may still be perceived by some as of primary importance, however both technology and empathy emerge as essential and equal components in the provision of quality coronary care. PMID- 8485352 TI - The nurse's role in caring for patients undergoing LDL-Apheresis. AB - LDL-Apheresis is a new, exciting, highly computerised treatment which is currently being researched. It selectively removes the harmful lipoproteins, in particular Low Density Lipoprotein (LDL) to which is attributed accelerated coronary artery disease 2-3 years after cardiac transplantation. Accepting the rather unique nursing role caring for patients receiving this treatment, the author has found that the research programme has opened up a challenging and very interesting variation in her career using advanced computerised technology. But it has also provided increased opportunity for her to use nursing skills, particularly in the area of communication, to enhance her relationship with the patients and raise the standard of care given. PMID- 8485353 TI - The role of nurses and technicians in intensive care. PMID- 8485354 TI - Implications of the James Bulger case for community nurses. PMID- 8485355 TI - Skill mix does not work. PMID- 8485356 TI - Management of the patient with altered body image. AB - Nurses are well placed to help patients come to terms with altered body image. However, in order to do so they must discard some of the prejudices that they hold. PMID- 8485357 TI - Developing a model for theatre nursing. AB - There has been much debate about the nature of theatre work and whether the activities performed by theatre nurses represent real nursing. This article examines the potential for constructing a nursing model to depict the variety of environments in which theatre nurse's work. PMID- 8485358 TI - Child sexual abuse. 1: Definitions, incidence and consequences. AB - It is estimated that over 6600 children under the age of 16 years are sexually abused each year in England and Wales (NSPCC, 1990). Of these incidents, 78% involve female children and 22% male children. The effects on the child range from self-mutilating behaviour and dissociative disorders to suicide. Consequently, nurses caring for victims of sexual abuse need to be aware of the trauma involved. PMID- 8485359 TI - Patient-controlled analgesia. AB - Patient-controlled analgesia is an effective method of controlling postoperative pain, providing its introduction is planned carefully and both staff and patients have been fully trained in the technique. PMID- 8485360 TI - Nursing a teenager with burns. AB - Development of body image is an integral part of a teenager's psychological growth. Burned teenagers experience great difficulty in readjusting psychosocially after injury as they have not yet formed their own self-concept and sense of worth. Burns patients experience a range of psychological problems as a consequence of disfigurement. These include depression, phobias, insomnia, sexual problems, high divorce rates, juvenile delinquency and impaired employment or academic status. Few nursing research articles have addressed the psychosocial problems of burns patients. Even if nurses are not skilled in counselling they must be able to recognize problems and refer patients to colleagues with the appropriate skills. PMID- 8485361 TI - Social perception and the nurse educator. AB - This article illustrates how psychological theory may be applied to nurse education. Nurse educators need to be aware of the impact of social perception, i.e. perception of others and perception of self, if they are to be objective and effective in teaching and assessing student nurses. PMID- 8485362 TI - The Bland truth: 2. PMID- 8485363 TI - Child sexual abuse and the right to compensation. AB - Adults who were sexually abused as children can sue the perpetrator in the civil courts. However, if they do not do so within the time period set down by the Limitation Act 1980, they may not be entitled to any compensation. Is the law, therefore, biased against them? PMID- 8485364 TI - Nurse-aid management of neurological emergencies. AB - People with altered levels of consciousness cannot be responsible for themselves. This article highlights the steps a nurse aider must take at the scene of an accident and discusses the importance of the environment in the neurological emergency. PMID- 8485365 TI - A career in renal nursing. AB - By the time we qualify, most of us are aware of the things we like and dislike about nursing. However, deciding on an area of specialism is difficult. This article examines renal nursing as an option for those nurses who know what factors they are looking for in a job. PMID- 8485366 TI - Definitions and explanations of the new financial vocabulary. AB - NHS reforms have led to a new vocabulary for nurses. This article explains the meaning of the terms budgetary control, establishment, pay and non-pay, zero based budgeting, trust regimens and the external financing limit. An understanding of these terms will help nurses implement the reforms. PMID- 8485367 TI - [Ultrasound-controlled percutaneous drainage of subhepatic liver abscess after conventional cholecystectomy]. AB - From February 1984 to August 1991 subhepatic abscesses were detected by ultrasound in 7 patients with fever following conventional cholecystectomy. Cholecystectomy had been performed in all these patients 6 to 27 days previously. All patients had received antibiotic prophylaxis at the time of cholecystectomy. Three of the 7 patients were at first afebrile, later on again febrile. In the remaining 4 of the 7 patients antibiotic treatment was continued in the face of persistent fever. Percutaneous catheter drainage was performed in all patients. In all of the 7 cases the subhepatic abscesses resolved completely within 10 days to 7 weeks. PMID- 8485368 TI - Sonographic aspects of the Cruveilhier Baumgarten syndrome. AB - A rare case of Cruveilhier-Baumgarten syndrome with exceptional deep subcutaneous portosystemic collaterals is reported. Undetected these anastomoses represent potentially dangerous sites for hemorrhage complications. Ultrasound in combination with color-coded duplex sonography is a reliable technique in identifying portosystemic anastomoses as well as in providing valuable information about the etiology of portal hypertension. PMID- 8485369 TI - [Value of magnetic resonance tomography for diagnosis of bone tumors]. AB - Primary bone tumors are well investigated with magnetic resonance imaging (MRI). Depending on the tumor site and localization the examination technique has to be tailored to the particular situation. Using MRI, the delineation of extraosseous tumor spread and the intramedullary extension of malignant bone tumors is superior as compared to other imaging modalities. PMID- 8485370 TI - Pyogenic hepatic abscess: long resolution time despite adequate therapy. AB - A 50-year-old male patient with a pyogenic hepatic abscess was successfully treated with an antibiotic regimen and percutaneous drainage of the abscess. Although this treatment was successful, it took more than 3 months for the abscess cavity to be completely resolved. A slow resolution of hepatic abscesses is therefore no evidence for the ineffectiveness of treatment. PMID- 8485371 TI - [Ultrasound diagnosis '92. 16th Three Country Karlsruhe Meeting, 21.-24. October 1992]. PMID- 8485372 TI - Micropreparative ion exchange high performance liquid chromatography: applications to microsequence analysis. AB - Data on the characterization of anion and cation micropreparative (50 x 1.6 mm i.d.) HPLC columns is presented. It is shown how subnanomole quantities of protein can be efficiently recovered from such columns, rendering them compatible for use in multidimensional chromatographic strategies for the purification of trace biological samples. By selection of appropriate solvent systems (e.g., buffer-free sodium chloride solutions), the small eluant peak volumes can be loaded directly onto the gas phase sequencer, and N-terminal sequence data obtained. The potential of the technique is illustrated for the purification of a GTPase activating protein (GAP-3). PMID- 8485373 TI - The determination of a new inhalational anaesthetic, sevoflurane, using an internal standard, xenon, by gas chromatography/mass spectrometry/selected ion monitoring. AB - A novel determination method for a new inhalation anaesthetic, sevoflurane, in a closed circuit in the presence of carbon dioxide absorbents is investigated using gas chromatography/selected ion monitoring with xenon as an internal standard. The decrease rate of sevoflurane with soda lime was 0.22% +/- 0.158/h (mean +/- SD), while that with baralyme was 0.57% +/- 0.115/h (mean +/- SD). PMID- 8485374 TI - Drug monitoring of clomipramine and desmethylclomipramine in depressed patients using a new liquid chromatographic assay. AB - A method has been developed for the quantitative analysis of clomipramine and its major metabolite desmethylclomipramine in plasma, using normal phase chromatography with UV detection at 254 nm. This rapid (6 min) and highly sensitive methodology (detection limits 0.5 ng/mL and 2 ng/mL for clomipramine and desmethylclomipramine, respectively; S/N = 3, 0.001 aufs) allows pharmacokinetic studies and drug monitoring of the two compounds. Using the described methodology we report an application which involved 10 depressed inpatients. PMID- 8485375 TI - Study of chemobiological reactions. 1. Selectivity of aromatic amino compounds and saccharides in glycosylation reactions. AB - The reactivities between saccharides and primary amino compounds were studied by liquid chromatography on an amino-bonded column and by measurement of the reaction rates of aromatic amines with saccharides. The recoveries from the column and the reaction rates were correlated with their physicochemical properties calculated by the CAChe program. The reactivities between amines and saccharides correlated well with their hydrogen bonding energies calculated by molecular mechanics. PMID- 8485376 TI - High performance gel filtration using monodisperse highly cross-linked agarose as a one-step system for mucin purification. AB - High performance gel filtration on monodisperse cross-linked agarose (Superose 6) has been assessed as a system for purification of mucus glycoproteins. Comparison with the conventional two-step purification of mucus glycoprotein by Sepharose CL4B gel filtration followed by caesium chloride density gradient centrifugation shows that purification by high performance gel filtration is at least as thorough, yielding mucin that is free from non-mucin glycoproteins as defined by buoyant density, mobility on sodium dodecyl sulphate-polyacrylamide gel electrophoresis and absence of Concanavalin A binding (mannose-containing) material. This technique allows mucus glycoprotein to be purified from lyophilized crude mucin in 120 min compared with approximately 72 h using the conventional techniques. This makes the comparative study of mucus glycoprotein changes in disease states much more feasible. PMID- 8485377 TI - Free-solution capillary electrophoretic separation of small hydrophilic peptides. AB - Small hydrophilic peptides differing in only one glycine amino acid group have been successfully separated by free-solution capillary electrophoresis (FSCE) using phosphate buffer at acid pH. The effects of column temperature and operating current on the migration times of these small peptides have been investigated. The results from FSCE have been compared with those from reversed phase high performance liquid chromatography. PMID- 8485379 TI - Simultaneous determination of NK611, a novel water-soluble derivative of etoposide, and its metabolite (DeNK611) in dog plasma by column-switching high performance liquid chromatography. AB - A simple, selective, reversed phase liquid chromatographic method using a column switching technique has been developed for the simultaneous determination of a novel derivative of etoposide (NK611) and its O-demethyl metabolite in dog plasma. A good linear response was obtained for both drugs in the range 0.1-12.0 micrograms/mL. The mean recoveries were within 100 +/- 5%. The within- and between-day precisions were within 3.5% and 4.6%, respectively. This method was used in a pharmacokinetic study following intravenous and oral administration of NK611 to beagle dogs. PMID- 8485378 TI - A high performance liquid chromatographic method for the determination of febantel and its major metabolites in lamb plasma. AB - A high performance liquid chromatographic (HPLC) method for the determination of the anthelminthic pro-benzimidazole febantel and its major metabolites in lamb plasma has been developed. Samples were extracted after addition of albendazole as internal standard, NH4OH and distilled diethyl ether. The extracted phase was dried under a stream of nitrogen redissolved in methanol and chromatographed by HPLC. Detection was by UV absorbance at 292 nm. Recovery from the plasma was 97.2, 97.1, 54.5 and 88.0% for febantel, fenbendazole, oxfendazole and oxfendazole sulphone respectively, and within-day and between-day coefficients of variation were 4.03, 4.69, 3.57 and 5.06% and 4.25, 3.73, 5.12 and 4.12%, respectively, for febantel, fenbendazole, oxfendazole and oxfendazole sulphone. The specificity and sensitivity of this method (limit of detection in plasma 0.025 micrograms/mL and < or = 0.0125 micrograms/mL for febantel and its metabolites, respectively) were sufficiently high to enable us to characterize the time course of the drug in the plasma after oral administration of therapeutic doses to sheep. PMID- 8485380 TI - Rapid liquid chromatographic assay of glutathione in cultured cells. AB - A rapid, sensitive and selective method for the assay of glutathione in cultured cells has been developed using ion-pair reversed phase rapid high performance liquid chromatography. The use of a 4 micron particle, 5 cm long column (Superspher 100 RP 18 end-capped) allowed complete analysis of glutathione within 3 min. A postcolumn derivatization reaction with o-phthalaldehyde and fluorometric detection made the assay fully selective with regard to other endogenous thiols and sensitive (the detection limit was 0.5 ng of glutathione injected). The linearity range was between 0.1 and 2.0 microgram/mL with good repeatability (relative standard deviation less than 5% for the lowest concentration quantitated). Recoveries of GSH from cultured cell samples were above 98%. The rapid analysis enabled the processing of a large number of samples in a short time (up to 20 per hour). The method was applied to the measurement of the intracellular glutathione amount in V79 fibroblasts along cell growth in culture. PMID- 8485381 TI - Determination of paracetamol (acetaminophen) in blood and plasma using high performance liquid chromatography with dual electrode coulometric quantification in the redox mode. AB - A simple, but sensitive, micro-assay for paracetamol in blood and plasma is described. Samples were prepared by precipitation with trichloroacetic assay solution and the drug quantified by reversed phase liquid chromatography with dual electrode electrochemical detection in the redox mode (oxidation at +0.25 V followed by reduction at -0.15 V). The limit of detection was 0.1 mg/L for a 10 microL sample of blood or plasma, the coefficient of variation at this concentration being 11.4%. The method was applied to a study of gastric emptying in patients before and after cardiac surgery. PMID- 8485382 TI - Purification and characterization of hedgehog liver metallothioneins. AB - Two forms of liver metallothioneins (MTs) were purified from hedgehog exposed to zinc, using gel filtration on Sephacryl S-100 and DEAE Sepharose Fast Flow chromatography. The peptide chain weight of both MT-1 and MT-2 was found to be about 10,000, as determined by high performance liquid chromatography. This value was higher than that calculated from amino acid analysis. The amino acid composition of hedgehog liver MT-1 and MT-2 resembles that of liver to MTs from rabbit and other species. Their distinctive features include an extremely high cysteine content, about 33% of all the amino acid residues, and an absence of aromatic amino acids and histidine. In addition, a rapid method for the determination of MTs during animal tissue purification has been established. The samples were directly added in an ammoniacal solution of a Co(II) salt for recording linear sweep polarograms. By comparison with the commonly used metal determination method, our method is direct, rapid, credible and suitable for all the MTs or MT-like samples. PMID- 8485384 TI - Evaluation and nursing education: where to now? PMID- 8485383 TI - Determination of felodipine enantiomers using chiral stationary phase liquid chromatography and gas chromatography/mass spectrometry, and the study of their pharmacokinetic profiles in human and dog. AB - A stereoselective and sensitive method for the determination of the enantiomers of felodipine, a dihydropyridine calcium antagonist, has been developed and the pharmacokinetic profiles of the enantiomers comparatively studied after oral administration to dogs and humans. D6-Felodipine, the internal standard, was added to the plasma, extracted with a solvent and then optically resolved into S( ) and R(+) enantiomers on a high performance liquid chromatographic Chiralcel OJ column. Each enantiomer in the effluent was analysed by capillary column gas chromatography/positive ion electron impact mass spectrometry. After oral administration of the felodipine racemate, the Tmax and t1/2 values hardly differed between the two enantiomers in dogs and humans. The Cmax and AUC0-24 h values of the S(-) enantiomer were slightly higher than those of the R(+) enantiomer in humans but the difference between the enantiomers was not significant. These results suggested that there is no large difference in the absorption, distribution and elimination of felodipine enantiomers after oral administration of the racemate in either dog or human. PMID- 8485385 TI - The newly formed College of Nurses. PMID- 8485386 TI - Where are the Maori nurses who were to become those "efficient preachers of the gospel of health?". AB - In an article published in Nursing Praxis in New Zealand Pamela Wood outlines the 1898 scheme for educating Maori nurses. This article gives an overview of the history of the nursing programme for Maori women. Wood states that "Far from being attempts to smooth the pillow of a dying race, [this programme was] grounded in a real concern to improve Maori health". I seek here to contribute to the debate on the development of Maori nursing education in New Zealand between the years of 1900 to 1910. In my opinion Maori nurses did not become 'efficient preachers' not because of lack of will, but rather because of the inequalities which existed between Pakeha and Maori nurse training schemes. The 'separatist' approach to the training of the Maori nurses, and the universal belief in the 'native' inability to learn, 'native' being a generic term for all races other than European, led to a scheme which failed to provide the number of Maori nurses envisaged at its inception. In little more than a decade from the scheme's inception to its Health Department launch the ideal of training for Maori women was abandoned. By examining resistance from within nursing and the wider socio political environment, this paper demonstrates how certain groups are consistently discriminated against. It further shows that reforms are not necessarily progressive but rather are double edged and always, in part, reflect the views of the most powerful. PMID- 8485387 TI - A moment of nursing: a case study. PMID- 8485388 TI - Cultural safety: a framework for changing attitudes. PMID- 8485389 TI - An ethnography of caring and control in an acute psychiatric unit. AB - The setting for this study was a 19 bed general hospital psychiatric ward serving a heterogeneous population. The objective of the study was to generate thick description of the cultural knowledge patients and nurses used to organise their behaviour and interpret their experience in an acute psychiatric unit. Further aims were to describe the nature of the service provided, and more specifically to identify relationships between caring and controlling in this social context, and the outcomes for patients of caring and controlling interventions by nurses. PMID- 8485390 TI - A peaceful death. PMID- 8485391 TI - Stevie. PMID- 8485392 TI - Relationship cataract density and visual field damage. AB - In interpreting visual field results, two questions arise: a) what type of visual field damage is produced by cataract, and b) can the influence on the visual field somehow be predicted? To answer these questions, cataract density was quantified with the Opacity Lens Meter (OLM) 701, and visual field tests were done before and after IOL-implantation surgery with Octopus Program G1 in 58 eyes of 58 patients (mean age 71 +/- 8 years) with cataract but with no other detectable ocular diseases. The average improvement of mean damage (MD) after surgery was 5.4 dB, and that of D (20) (defect 20 on the Bebie Curve) was 5.7 dB. The improvement of the visual fields was, as expected, statistically highly significant (p < 0.0001). The corrected loss variance (CLV), however, increased on the average only by 2.5 dB2, which was not significant. The predictive value of the OLM reading for opacity-induced MD depends on the type of cataract. It is good for cortical and nuclear cataracts but poor for posterior subcapsular opacifications. The overall predictive value (R = 0.66) is, nevertheless, better than for preoperative visual acuity (R = -0.54). If OLM and visual acuity (VA) are considered together, the predictive value is slightly higher (R = 0.72). Thus, optical density influences on visual field performance can be subtracted from general visual field results. PMID- 8485393 TI - Clinical correlations in HIV-1 and HIV-2 infected patients. AB - In Portugal, the prevalence of human immunodeficiency virus type 2 (HIV-2) seropositivity is higher than in other European countries or North America. Recent literature data points out a possible difference on the pathogenic potential and on the natural history of HIV-1 and HIV-2, suggesting a lower virulence of HIV-2. Facing these hypothesis and the increasing number of HIV-2 cases, we analysed two infected groups HIV-1 and HIV-2, trying to correlate the ophthalmologic lesions present in both populations and searching for a difference in the clinical presentation of the ocular disorder. We studied prospectively 214 patients with HIV infection at several stages, 83% HIV-1 and 17% HIV-2. Ocular manifestations were present in both populations with a significant prevalence in HIV-1 (48%), compared to HIV-2 (19%) (p < 0.005). The ophthalmologic pathology found, particularly noninfectious retinopathy, infectious retinitis and neuro ophthalmic disorders, were considered important for the disease's diagnosis and prognosis. All these ophthalmic findings were present in the HIV-1 population. In the HIV-2 group the most frequent lesion was noninfectious retinopathy. Within each group, HIV-1 and HIV-2, the comparison of the survival between AIDS patients with and without ocular lesions, revealed a significant shorter survival time in those with ocular pathology (p < 0.001 and p < 0.05). There seems to exist a certain analogy in clinical expression in both groups, although it is possible to admit a lower severity in ocular involvement in patients infected by HIV-2. PMID- 8485394 TI - Visual field indices for the nasal step: different calculation procedures and their correlation with the clinical classification of visual field defects. AB - We calculated normal values for the normal population of the Octopus G1 program (n = 836) and values for defective fields due to glaucoma and other diseases (n = 147) to determine indices for a nasal step in the interpretation of glaucomatous visual fields. We used different calculation procedures and correlated the results with the clinical evaluation of the visual field. All indices tested were able to detect and quantify nasal steps in defective fields and to separate them from normal findings (area under curve of Receiver Operating Characteristic curves 0.963 to 0.999). Indices calculated excluding sensitivity values of positions with the greatest distance from the horizontal meridian or weighting of sensitivity values according to their closeness to the horizontal meridian showed the best results (auc = 0.999). We can thus conclude that the calculation of an index for nasal step is a simple and effective adjunct to any interpretation system for visual fields. PMID- 8485395 TI - Imipenem reaches therapeutic concentrations in aqueous humor, as determined by HPLC. AB - The majority of ocular infections in the industrialized countries arise after surgical interventions. An appropriate antibacterial prophylaxis is therefore highly desirable in eye surgery. We used high performance liquid chromatography (HPLC) to measure the concentrations reached by imipenem, a modern wide-spectrum beta-lactam antibiotic, in plasma and aqueous humor of 26 patients scheduled for cataract surgery. Even a single 500 mg dose of imipenem achieved therapeutic levels of the molecule for the most common ophthalmic pathogens (1 microgram/ml or above) in the aqueous humor within one to two hours after administration. This drug may therefore be suitable for antibacterial prophylaxis in eye surgery. PMID- 8485396 TI - Sagittal magnetic resonance imaging of dysthyroid ophthalmopathy. AB - Sagittal magnetic resonance imaging (MRI) scans of the eye and orbit were made of 30 eyes in 15 cases of dysthyroid ophthalmopathy (DO). On the basis of these scans, we sought to elucidate relationships between the morphological condition of the levator palpebrae muscle, fatty tissue in the upper eyelid and the superior, inferior recti muscles and the occurrence of such symptoms as lid retraction, lid swelling and vertical disturbance of eye movement. The levator palpebrae muscle was enlarged in all 15 DO eyes (100%) with upper eyelid retraction. In 16 (88.9%) of 18 eyes with apparent lid swelling, enlargement of the preaponeurotic fat or submuscular fat pad was clearly evident. In the control eyes, no such enlargement was seen in either the levator palpebrae muscle or orbital fatty tissue. The clear space between the superior recti and the levator palpebrae muscles that was seen in control eyes was absent in all five eyes that presented a disturbance in infraduction. In 8 (80%) of 10 eyes with a disturbance in supraduction, the inferior rectus muscle was enlarged and muscle extension was impaired. Sagittal MRI seemed to be a useful means of obtaining a better clinical understanding of a variety of eye symptoms associated with DO. PMID- 8485397 TI - Is the type of VDT work important in asthenopia? AB - The Authors studied the relationship between visual fatigue (or asthenopia) and different types of work with display units on about 30,000 videoterminal (VDT) operators of the Italian telecommunication company. Visual fatigue was reported with data entry, data checking, word processing, dialogue enquiry, and various services. The Chi-square test showed that asthenopia was not related to any particular type of VDT work, comparing subjects working at the VDT for similar times each week. These findings provide further confirmation that the main factor determining visual fatigue in VDT operators is the amount of time spent at the display units. PMID- 8485398 TI - The fate of eyes with anterior chamber intra-ocular lenses. AB - A total of 143 anterior chamber (AC) intra-ocular lenses (IOL) of various designs were implanted in a five-year period and followed for 18 to 76 months. The lenses were inserted as a secondary implant after extracapsular cataract extraction (ECCE) complicated by vitrectomy, or after primary intra-capsular extraction. The complications (corneal edema, uveitis/glaucoma, extrusion/imbedding, cystoid macular edema), the final visual acuity and the need for removal of the IOL were analyzed. Only small differences were found between the different lenses but some association was found between complicated surgery (ECCE + vitrectomy) and a higher rate of complication, poorer visual outcome and more frequent need for IOL removal. Cystoid macular edema was encountered only in cases with complicated ECCE. A high percentage of other ocular pathologies was found among the cases, possibly implying that diseased eyes are more prone to surgical complications. An alternative to the AC-IOL in cases with a ruptured posterior capsule is the suture-supported posterior chamber IOL, but the flexible-loop AC-IOL may not yet be obsolete. PMID- 8485399 TI - Full-thickness macular hole and retinal detachment complicating Best's disease. AB - The unusual association of Best's vitelliform macular dystrophy and a full thickness macular hole causing retinal detachment is reported. Successful reattachment was achieved with pneumatic retinopexy and postoperative laser photocoagulation. The mechanisms underlying the combination of full-thickness macular hole and retinal detachment in Best's disease remain to be elucidated. PMID- 8485400 TI - Electroretinographic changes during childhood and adolescence. AB - Electroretinogram (ERG) changes with age have been studied widely, but there is no general agreement about the age at which ERG parameters reach adult values. We studied 296 eyes from 148 healthy subjects, divided into 14 age groups, ranging from 1 week to 21 years. Although most of the maturational changes or ERG take place during the first six months, the a wave completes development at three years of age and the b component shows a smooth increase in latency between 3 and 18-21 years. The latter component also shows an increase in amplitude from 7-8 to 12-14 years. During the first period of maturation the b wave parameters follow a multiplicative model. These data are discussed in relation to previously reported findings on ERG maturation and to morphological and functional eye changes with age. PMID- 8485401 TI - Regulation of carotenoid biosynthesis during tomato development. AB - Phytoene synthase (Psy) and phytoene desaturase (Pds) are the first dedicated enzymes of the plant carotenoid biosynthesis pathway. We report here the organ specific and temporal expression of PDS and PSY in tomato plants. Light increases the carotenoid content of seedlings but has little effect on PDS and PSY expression. Expression of both genes is induced in seedlings of the phytoene accumulating mutant ghost and in wild-type seedlings treated with the Pds inhibitor norflurazon. Roots, which contain the lowest levels of carotenoids in the plant, have also the lowest levels of PDS and PSY expression. In flowers, expression of both genes and carotenoid content are higher in petals and anthers than in sepals and carpels. During flower development, expression of both PDS and PSY increases more than 10-fold immediately before anthesis. During fruit development, PSY expression increases more than 20-fold, but PDS expression increases less than threefold. We concluded that PSY and PDS are differentially regulated by stress and developmental mechanisms that control carotenoid biosynthesis in leaves, flowers, and fruits. We also report that PDS maps to chromosome 3, and thus it does not correspond to the GHOST locus, which maps to chromosome 11. PMID- 8485402 TI - Protein isoprenylation in suspension-cultured tobacco cells. AB - Many mammalian and yeast proteins, including small ras-like GTP binding proteins, heterotrimeric G protein gamma subunits, and nuclear lamins, have been shown to be covalently linked to isoprenoid derivatives of mevalonic acid. Isoprenylation of these proteins is required for their assembly into membranes and, hence, for their biological activity. In this report, it is shown that cultured tobacco cells, when pretreated with an inhibitor of endogenous mevalonic acid synthesis (lovastatin), incorporate radioactivity from 14C-mevalonic acid into proteins. Most of these proteins are membrane associated, and many are similar in mass to mammalian ras-like GTP binding proteins and nuclear lamins. Furthermore, it is shown that tobacco cell extracts catalyze the transfer of radioactivity from 3H farnesyl pyrophosphate and 3H-geranylgeranyl pyrophosphate to protein substrates in vitro. These studies indicate the presence of at least two distinct prenyl:protein transferases in tobacco extracts: one that utilizes farnesyl pyrophosphate and preferentially modifies a substrate protein with a CAIM carboxy terminus (farnesyl:protein transferase) and one that utilizes geranylgeranyl pyrophosphate and preferentially modifies a substrate protein with a CAIL carboxy terminus (geranylgeranyl:protein transferase type I). This work provides a basis for future work on the role of protein isoprenylation in plant cell growth, signal transduction, and membrane biogenesis. PMID- 8485403 TI - The N- and C-terminal regions regulate the transport of wheat gamma-gliadin through the endoplasmic reticulum in Xenopus oocytes. AB - Following sequestration into the endoplasmic reticulum (ER), wheat storage proteins are naturally either retained and packaged into protein bodies within this organelle or exported to the Golgi apparatus. To identify protein domains that control the sorting of wheat storage proteins within the ER, a wild-type gamma-gliadin storage protein as well as two of its deletion mutants, each bearing either of the two autonomous N- and C-terminal regions, were expressed in Xenopus oocytes. Our results demonstrated that the N-terminal region of the gliadin, which is composed of several tandem repeats of the consensus sequence PQQPFPQ, was entirely retained within the ER and accumulated in dense protein bodies. In contrast, the C-terminal autonomous region was efficiently secreted to the medium. The wild-type gamma-gliadin, containing both regions, was secreted at a lower rate and less efficiently than its C-terminal region. These results suggest that sorting of the wheat gamma-gliadin within the ER may be determined by a balance between two opposing signals: one functions in the retention and packaging of the storage protein within the ER, while the second renders the protein competent for export from this organelle to the Golgi apparatus. PMID- 8485404 TI - Dissection of the functional architecture of a plant defense gene promoter using a homologous in vitro transcription initiation system. AB - CHS15 is one of a family of bean genes encoding chalcone synthase, which catalyzes the first reaction in a branch pathway of phenylpropanoid biosynthesis for the production of flavonoid pigments and UV protectants and isoflavonoid derived phytoalexins. The functional architecture of the CHS15 promoter was dissected by a novel homologous plant in vitro transcription initiation system in which whole-cell and nuclear extracts from suspension-cultured soybean cells direct accurate and efficient RNA polymerase II-mediated transcription from an immobilized promoter template. Authentic transcription from the CHS15 promoter template was also observed with whole-cell extracts from suspension-cultured cells of bean, tobacco, and the monocot rice, and the soybean whole-cell extract transcribed several other immobilized promoter templates. Hence, this procedure may be of general use in the study of plant gene regulation mechanisms in vitro. Assay of the effects of depletion of the soybean whole-cell extract by preincubation with small regions of the CHS15 promoter or defined cis elements showed that trans factors that bind to G-box (CACGTG, -74 to -69) and H-box (CCTACC, -61 to -56 and -121 to -126) cis elements, respectively, make major contributions to the transcription of the CHS15 promoter in vitro. Both cis element/trans factor interactions in combination are required for maximal activity. Delineation of these functional cis element/trans factor interactions in vitro provides the basis for study of the mechanisms underlying developmental expression of CHS15 in pigmented petal cells established by G-box and H-box combinatorial interactions, and for characterization of the terminal steps of the signal pathway for stress induction of the phytoalexin defense response. PMID- 8485405 TI - The evolution of informed consent: beyond an ethics of care. PMID- 8485406 TI - Response to "Ethical Dimensions of Informed Consent". PMID- 8485407 TI - An aside on the role of autonomy in informed consent. PMID- 8485408 TI - "Ethical dimensions of informed consent": a psychiatric perspective. PMID- 8485409 TI - Ethics versus law: a lawyer's road map to the Ethics Committee opinion on informed consent. PMID- 8485410 TI - Confusing law and ethics: why the Committee's report on informed consent should be reconsidered. PMID- 8485411 TI - Commentary: "Ethical dimensions of informed consent". PMID- 8485412 TI - Informed consent: commentary on the ACOG Ethics Committee statement. PMID- 8485413 TI - Commentary on "Ethical issues of informed consent". PMID- 8485414 TI - Commentary: Ethical issues of informed consent. PMID- 8485415 TI - Organization and delivery of perinatal health care services at the community level. National Perinatal Information Center and University of South Florida School of Public Health. PMID- 8485416 TI - Prenatal diagnosis and abortion. PMID- 8485417 TI - Image: celebrates 25th anniversary. PMID- 8485418 TI - Data versus information versus knowledge. PMID- 8485419 TI - The knowledge bank ... a library update. PMID- 8485420 TI - National Library of Medicine offers nursing resources. PMID- 8485421 TI - The Online Journal of Knowledge Synthesis for Nursing. PMID- 8485422 TI - INTERNET: linking nurses, scholars, libraries. PMID- 8485423 TI - Are drug policies based on 'fake' statistics? PMID- 8485424 TI - Should the controlled provision of heroin be a treatment option? Australian feasibility considerations. AB - A proposal for a trial to provide heroin to dependent users in a controlled manner is currently being considered in the Australian Capital Territory. The political background to this proposal is outlined, as is the current 'drug scene'. A Stage 1 examination found that a trial of controlled provision of heroin is feasible in principle and recommended a further stage (Stage 2) of feasibility investigations to explore the practicalities. The results of the Stage 1 investigations and the proposals for Stage 2 are incorporated into discussion about three important issues: the feasibility research process, the therapeutic relationship, and social control. These considerations have wider applicability, both for treatment services for illegal drug users generally and for informing drug policy debates. Much can be learnt from the feasibility considerations, whether or not a trial of the controlled provision of heroin eventuates in Australia. PMID- 8485425 TI - Modelling the interactions between alcohol, crime and the criminal justice system. AB - Similarities in the trends of the number of offences and the level of alcohol consumption are often used as evidence as a link between alcohol and many forms of criminal activity. However, such crude correlations may be misleading as they neither take account of other factors that might be important, not assist the understanding of the causal links between alcohol and crime. In this paper, the role that economic models may play in furthering the understanding of the potential links between alcohol and crime are explored. A complete model is presented which allows for complex interactions between alcohol, crime and the criminal justice system. Results from testing this model with time series data (1960-88) for England and Wales for different types of crime are discussed in detail. Data defined by standard regions and for the years 1980 to 1988 were also compiled and a summary of the results discussed. The argument that alcohol consumption may be one of the determinants of a wide range of crimes receives some support and is also found that alcohol consumption may affect the probability of detection for some types of crime. PMID- 8485426 TI - Physical, subjective, and social availability: their relationship to alcohol consumption in rural and urban areas. AB - The alcohol availability literature indicates that under some conditions, physical availability is positively associated with per capita alcohol consumption. Smart (1980) suggested that at the individual level, subjective and social aspects of availability may mediate and outweigh the influence of physical availability. The study described here examined the simultaneous effects of physical, subjective, and social availability on alcohol consumption. Standardized telephone interviews were conducted with 781 adult drinkers. As hypothesized, physical availability was not a significant multivariate predictor of alcohol consumption for residents of high, medium, and low alcohol outlet density counties in Michigan (USA). Subjective and social availability indicators were significant predictors of alcohol consumption. Similar patterns of results were found in multiple regression analyses for blacks and whites and women and men, although blacks and women consumed less alcohol than did whites and men. The theoretical and practical implications of these results are discussed. PMID- 8485427 TI - The origin of alcohol-related social norms in the Saami minority. AB - The present paper addressed the problem of the origin of alcohol-related social norms in the Saami minority in northern Norway. Based on data from studies of comparable ethnic minorities in Greenland, North America and Australia it could be expected that alcohol use- and abuse would be more prevalent in the Saami than in the Norwegian populations of northern Norway. No data to support this hypothesis exist. On the contrary, available data suggest that drinking problems in this group are similar to those of the majority in the area. The present paper developed the hypothesis that Saami alcohol-related social norms originated in the Laestadian religious revival. The paper investigated the impact of the Laestadian culture in the formation of alcohol-related social norms. It was concluded that the Laestadian sobriety norm, and the norm of abstinence from the use of adiafora, have influenced alcohol-related behaviour in the Saami group in such a way that this group does not conform to the drinking behaviour found in comparable minorities. PMID- 8485428 TI - Patterns of drug use and risk-taking among injecting amphetamine and opioid drug users in Sydney, Australia. AB - Data are presented on the patterns of drug use and HIV risk-taking of daily amphetamine and opioid injectors among 1245 injecting drug users who were interviewed in Sydney in 1989. About one-third of the sample had injected amphetamines during a typical month of injecting, and 12% were using amphetamines on a daily basis. Daily amphetamine injectors were younger, less well educated, and less likely to have engaged in drug treatment, but they were no more likely than daily opioid users to have shared injection equipment or to have engaged in other behaviour likely to transmit HIV. Although there seemed to be no special cause for concern about HIV risk-taking among amphetamine injectors, there was nonetheless a high prevalence of sharing injecting equipment, with over half of daily amphetamine and heroin injectors having shared in the past several months. In addition, approximately a third of amphetamine injectors were injecting on a daily basis, a pattern of use which increases the risk of developing a severe dependence syndrome, and of experiencing an amphetamine-induced psychosis. PMID- 8485429 TI - Socially desirable responding and self-reported HIV infection risk behaviors among intravenous drug users. AB - This study examined the extent to which self-report of human immunodeficiency virus (HIV) risk behaviors might depend upon socially desirable response tendencies, and whether socially desirable responding might serve as a confounding variable in the study of risk behaviors and HIV serostatus. The subjects were 2885 intravenous drug users participating in the ALIVE study in Baltimore, Maryland. Participants completed an interview and were tested for HIV serostatus. The interview covered HIV risk behaviors, and included established scales to measure 'self-deception' and 'impression management', two separate dimensions of socially desirable responding. Seven items for each scale were scored true/false, with a summary score used for analysis. Scores on self deception and impression management were inversely related to self-reports of sharing injection equipment, injecting at shooting galleries, and injecting more than once a day. Neither self-deception nor impression management was associated with cocaine use. Self-reported receptive anal intercourse was associated inversely with self-deception but not with impression management. HIV serostatus was not associated with social desirability, and statistically controlling for social desirability had a negligible impact on the magnitude of associations between risk behaviors and HIV serostatus. The results indicate that measures of social desirability may be used to ascertain sensitive areas of inquiry in interviews of intravenous drug users. PMID- 8485430 TI - Effect of low and moderate doses of alcohol on driving hazard perception latency and driving speed. AB - Both driving speed and speed of detection of potentially hazardous events while driving have been found to correlate positively with accident rates across individuals. Alcohol ingestion is also known to increase risk of a traffic accident. This paper reports two double-blind, placebo-controlled studies: one on the effect of alcohol on driving speed and the other on the effect of alcohol on time taken to detect potential traffic hazards. Moderate drinkers aged between 30 and 55 took part. Each subject underwent three experimental conditions on separate days: no alcohol, low alcohol (0.025% BAC) and moderate alcohol (0.05% BAC). The order of conditions was counterbalanced. The moderate alcohol dose increased mean time taken to respond to hazards (2.5 s in no alcohol condition compared with 3.2 s in moderate alcohol condition) but did not affect mean driving speed (indexed by time taken to travel sections of a fixed route; 19.3 s in no alcohol compared with 19.0 s in moderate alcohol). The results support the view that at least part of the excess risk of accident associated with alcohol ingestion is attributable to an increase in the time taken to respond to traffic hazards. PMID- 8485431 TI - Recycling with nicotine patches in smoking cessation. AB - The aim was to evaluate if recycling of failures from a smoking cessation study may be of value. The study comprised 126 smokers (50%) of 252 failures, from a double-blind smoking cessation trial with nicotine patch, who accepted recycling after 1 year. Subjects were allocated nicotine patches delivering 15, 20 or 25 mg of nicotine (over 16 hours) according to their base-line saliva cotinine concentrations in an open trial. The treatment period was 12 weeks followed by tapering over 6 weeks. The percentage of quitters after 3, 12, 26, and 52 weeks was 44, 20, 7 and 6%, respectively. After 26 weeks, all subjects had relapsed in the group previously treated with active nicotine patch compared with 12% abstainers in the previous placebo subjects. The sustained abstinence rate without slips after one year was 2%. Recycling does not seem to be of long-term clinical relevance in our set-up for subjects initially treated with nicotine, but of some value in subjects quitting without nicotine therapy initially. PMID- 8485432 TI - Sensation seeking, gambling and gambling addictions. AB - Male off-course bettors were assessed using: the Sensation-Seeking Scale (SSS) Form V, two measures of subjective arousal while betting, and questions concerning chasing, preferences for gambling activities and other aspects of betting behaviour. The SSS was also administered to a random sample of the male general population of Glasgow, together with questions concerning preferences for gambling activities to allow comparison between regular gamblers and the general population. In comparison with the general population and with non-gamblers, off course bettors scored lower on SSS; gamblers preferring the casino and/or the race-track scored higher on SSS; gamblers betting on many different forms scored higher on SSS. A further analysis produced a cluster of variables among off course bettors associated with impaired control of gambling, among which both SSS scores and chasing were prominent features. PMID- 8485433 TI - Alcoholics anonymous, other 12-step movements and psychotherapy in the US population, 1990. AB - Based on the 1990 US National Alcohol Survey, this note provides the first available comprehensive findings on self-reported utilization of a variety of sources of personal support and counselling for alcohol and other problems. Respondents were queried about lifetime attendance and number of times they went to identified sources of help in the prior year. Twelve-step groups included Alcoholics Anonymous, Al-Anon, Adult Children of Alcoholics, and other non alcohol-oriented groups like Gamblers Anonymous, Narcotics Anonymous, and Overeaters Anonymous; additional questions inquired about support or therapy groups and individual counselling for non-alcohol problems. Of the US adult population, 9% have been to an AA meeting at some time, 3.6% in the prior year, only about one-third of these for problems of their own. About half these percentages, mostly women, have attended Al-Anon. Of the same population, 13.3% indicate ever attending a 12-step meeting (including non-alcohol-oriented groups), 5.3% in the last year. During the prior year a further 2.1% used other support/therapy groups and 5.5% sought individual counselling/therapy for personal problems other than alcohol. In contrast to this high reported utilization, only 4.9% (ever) and 2.3% (12-months) reported going to anyone including AA for a problem (of their own) related to drinking. PMID- 8485434 TI - Selden Daskam Bacon (1909-1992). PMID- 8485435 TI - Q-switched CTE:YAG laser sclerostomies on human autopsy eyes. AB - Experimental laser sclerostomies were performed on human eye-bank eyes with a new mid-infrared solid-state laser that is characterized by adequate optic-fiber transmission and low-thermal tissue interaction. The laser presented herein works with a chromium thulium erbium-doped (CTE): YAG crystal as the active medium, emitting radiation at a wavelength of 2.69 microns. In the Q-switch mode, the pulse duration is tunable from 0.5 to 2.5 microseconds. The maximal energy is 50 mJ/pulse (1-10 Hz). Attenuation of energy transmission in quartz (0.3 ppm) optic fibers is < 8 dB/m (diameter, 200 microns). Absorption depths of 2.69 microns radiation in water is 12.5 microns. In vitro procedures performed were ab-interno and ab-externo full-thickness sclerostomies. Histological and micro-morphological examination was performed by light microscopy and scanning electron microscopy. Collateral tissue damage in processed sclerostomies did not exceed 50(+/- 10) microns at typical fluences (10 J/cm2). In contact guidance, 10-15 laser pulses were required in the full-thickness ab-externo procedure, whereas up to 50 pulses were required in the ab-interno procedure. The number of laser pulses applied corresponded to the length of the filtration canals created. The canal was significantly longer (2.5 +/- 1 mm) in the ab-interno approach than in the ab externo approach (1 +/- 0.2 mm). The intraocular ostium of the filtration canal in the ab-externo procedure showed enhanced signs of mechanical deterioration. It is concluded that both the wavelength (2.69 microns) and the pulse duration (0.5 2.5 microseconds) of the CTE: YAG laser are appropriate for laser sclerostomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485437 TI - Simulation of the growth pattern of the central retinal artery using a fractal modeling technique. AB - Assisted by computer, we simulated the typical growth pattern of the central retinal artery by a fractal modeling technique. When processing was started with two fertile sides, an iterative processing function generated a ramiform fractal. The branching angle was chosen at random within a certain range. In addition, a feedback restriction forbade any intersection of branches. We demonstrated that the curved shape of the temporal vessels is caused by simultaneous growth of the vessels and the retina. When processing was begun with only one fertile side, the typical vascular pattern of a retinal coloboma was designed. PMID- 8485436 TI - Hexadecylphosphocholine may produce reversible functional defects of the retinal pigment epithelium. AB - Hexadecylphosphocholine is a synthetic phospholipid derivative that has antitumor activity due to its interference with membrane functions. Animal experiments have shown photoreceptor and retinal pigment epithelium (RPE) degeneration after its systemic application. In a phase II trial of hexadecylphosphocholine therapy in 23 patients with advanced metastatic colorectal or lung cancer, visual acuity and color vision testing, slit-lamp examination, tonometry, fundoscopy (including photodocumentation), visual field testing, electrooculography (EOG), and electroretinography (ERG) were performed. A baseline examination was carried out prior to therapy. Patients were reexamined after 2 months and after 5 months. In all, 71% of the patients had a reduced light peak in the EOG during therapy. After the end of therapy the light peak improved again and became normal in most patients. The statistical analysis showed that the light-peak values during therapy were significantly lower than the baseline and posttreatment values. This indicates that hexadecylphosphocholine might be capable of producing a partly reversible functional defect of the RPE. Apart from this finding, no other functional or morphological ocular side effect was detected. The functional changes observed in our patients as well as the morphological changes found in animal experiments are similar to those reported for known diseases of the RPE photoreceptor complex. Therefore, hexadecylphosphocholine-induced retinopathy might become useful as an animal model for such diseases. PMID- 8485438 TI - Vitreous body-derived mitogenic activity for retinal pigment epithelial cells. A further characterization. AB - To obtain a better insight into the possible role of vitreous body in proliferative vitreoretinopathy (PVR), we examined the influence of bovine vitreous body fractions separated by fast protein liquid chromatography (FPLC) on the growth of porcine retinal pigment epithelial (RPE) cells in vitro. Tetrazolium colorimetric assay (MTT assay) and cell counting were used for quantification. After fractionating proteins of the physiological vitreous body by FPLC gel chromatography (Superose 12/Superdex 75), we determined the mitogenic effect of the resulting fractions by either cell counting or MTT assay. With both columns we were capable of separating two fractions (20-40 kDa and 1-2 kDa) that induced RPE cell proliferation. A comparison of the mitogenesis and the protein content of the fractions indicated that we were not dealing with a nonspecific protein effect. The low-molecular fraction weighing less than 2 kDa was of particular interest to us. This was further separated by FPLC reversed-phase chromatography. PMID- 8485439 TI - Studies on the origin of the glycoproteins of the rabbit vitreous body using a protein-synthesis inhibitor and radioactive fucose and amino acids. AB - Rabbits were injected intravitreally with [3H]-fucose and were killed at 0.5, 4, 24, and 40 h postinjection. The radiometric measurements and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) plus fluorography performed on the vitreous bodies of these rabbits were compared with those carried out on excised vitreous bodies of noninjected rabbits incubated with [3H]-fucose for the same periods. The results of these in vitro experiments demonstrated that at all test intervals there were only two lightly labeled bands in the fluorograms, and this was interpreted as nonenzymatic binding of [3H]-fucose to proteins (glycation), occurring in the extracellular environment. In contrast, intravitreal injections resulted in about 14 conspicuously labeled bands, mainly after the longer time intervals, and the nature of these bands was revealed by additional experiments. In another series of experiments, rabbits were injected intravitreally with either [3H]-fucose or [3H]-amino acids and their vitreous bodies were processed as described above. The specific activity (counts per minute per microgram of protein) of the glycoproteins labeled with [3H]-fucose was always higher than that of the proteins labeled with any of the amino acids. In fluorograms, eight bands unequivocally labeled with the [3H]-amino acids were detected, and corresponding bands almost invariably appeared in the [3H]-fucose lane. Cycloheximide, a protein-synthesis inhibitor, blocked almost completely the incorporation of both [3H]-proline and [3H]-fucose into the vitreous proteins as revealed by the radiometric measurements and fluorography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485440 TI - Successfully treated sympathetic ophthalmia with typical histological confirmation. PMID- 8485441 TI - Four years' experience with triple procedures in herpes-afflicted eyes. AB - Keratoplasties are performed relatively frequently in herpes-afflicted eyes. However, intraocular lenses (IOLs), for eyes with intraocular recurrent herpes simplex virus (HSV) disease remain a verdict in most surgical centers. As most herpetic disease is uniocular and cataract is a frequent complication in the long run, a real need exists for triple procedures in such eyes so as to achieve their full visual rehabilitation. Taking full advantage of systemic aciclovir therapy and prophylaxis, we started with triple procedures in herpes-afflicted eyes in 1987. Up to July 1991, we operated on 29 eyes, and 28 could be optically rehabilitated. One eye was given up and received a conjunctival cover for sociomedical reasons. Three repeat keratoplasties (10%) were necessary, and a considerable number of complications had to be overcome; ten eyes suffered from sustained fibrinous exsudations (35%), ten were threatened by one or more endothelial immune therapy reactions (35%), and ten experienced one or more herpes recurrences (35%), mostly intraocular recurrences. As this study was not performed as a randomized, placebo-controlled, double-blind study, no absolute scientific proof of aciclovir's value in these patients can be presented. Nonetheless, we would conclude from the exceedingly good rehabilitation rate of 96% observed during an average follow-up period of 19 months that in all probability, systemic aciclovir was in the first rank responsible for this success rate. Thus, there is good clinical evidence that systemic aciclovir prophylaxis and therapy is indeed the most important key for successful triple procedures in eyes afflicted with herpetic disease. PMID- 8485442 TI - Preliminary results following implantation of iris-suture-fixated posterior chamber lenses. AB - Iris-suture-fixated posterior-chamber lenses with a 7-mm optic zone and modified C-loops with 2 holes were implanted in 30 patients (8 men and 22 women), of whom 13 received simultaneous corneal transplantations. The mean follow-up period was 13.3 months. The iris was penetrated from behind and the intraocular lens was sutured with two double-armed 9-0 prolene sutures, the knot being positioned on the anterior surface of the iris. Most patients showed an increase in visual acuity except for two who had pre-existing retinopathy and one who developed a seclusio pupillae. The complications seen were: mild distortion of the pupil (7), iris capture (1), posterior synechiae (1) and ablatio chorioideae (1). This new technique yields good results in cases of intraoperative rupture of the capsule. In patients undergoing simultaneous corneal transplantation, a longer follow-up period is needed. PMID- 8485443 TI - Perforating injuries: causes and risks are changing. A retrospective study. AB - We reanalyzed all 384 records of perforating injuries primarily admitted to the University Eye Hospital of Freiburg during the years 1981-1983 and 1987-1989. Complete data could be obtained from 369 records. Injuries from 1987-1989 were compared with those from 1981-1983 with regard to the cause and extent of the perforation as well as sex, age, occupation, and activity of the patient at the time of injury. The following significant trends were observed. Seat-belt legislation in 1984 was extremely beneficial for the prevention of penetrating occular injuries, especially among women aged 16-25 years. Of 39 injuries to women, 17 (43%) were related to traffic accidents in 1981-1983 as opposed to only 1 of 16 injuries (6%) in 1987-1989. Therefore, the male/female ratio increased from 4.1 to 9.6 (P = 0.006). Perforations during traffic accidents declined from 26% (52/199) to 11% (19/170). The number of occupational injuries remained constant, although their proportion increased from 42.7% (85/199) in 1981-1983 to 50% (85/170) in 1987-1989. High-risk activities at work as well as during leisure time changed from hammering to work with rotating machines (drills, lathes) and wires. The incidence of agricultural injuries rose from 4% to 9% (from 8 to 15). Injuries during leisure activities remained constant (66 vs 62). Among this group, injuries related to a hobby increased, whereas perforations occurring during visits to pubs or festivities decreased. Pediatric injuries remained constant and were responsible for 15.6% and 14.7%, respectively, of all injuries (age, < or = 15 years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485444 TI - Visual learning in the hyperacuity range in adults. AB - We investigated the amount, speed, and specificity of the learning of new visual tasks in adult humans using stereoscopic depth perception and vernier discrimination as the sensitive probes for learning. The results of psychophysical experiments in untrained adult observers indicate two phases of highly specific perceptual learning in humans: a fast phase and a slower one. Both types of learning might take place relatively "early" during pattern recognition in the visual cortex, since learning was very specific, without transfer between different stimulus orientations. PMID- 8485445 TI - Variation of temporal stimulus characteristics to evaluate visual function prior to pars plana vitrectomy. AB - Electrophysiological examinations were carried out prior to pars plana vitrectomy in a series of consecutive patients with complicated diabetic retinopathy, proliferative vitreoretinopathy, and perforating injuries. In 141 eyes electroretinograms were evaluated. The amplitude of the a- and b-waves at dark and light adaptation and of the 30-Hz flicker response correlated with the postoperative visual acuity and the retinal morphology. Due to the variability of these parameters, however, the preoperative electroretinogram has no predictive value. In 245 eyes, flash and flicker (5, 10, 20, 30 Hz) visual evoked cortical potentials (VECP) were recorded. The flash VECP was of no value. The presence of a response to a flicker stimulus of 10 Hz or higher frequencies, however, indicated a better functional recovery (P < 0.02). More eyes with an attached central retina showed a 30-Hz flicker response as compared to eyes with central retinal detachment (P < 0.01). The flicker VECP therefore, has a predictive value prior to vitrectomy. PMID- 8485446 TI - Evaluation of numerical displays of visual field data by human observers--the definition of scotomas and clusters by human interpreters. AB - Numerical printouts of 23 visual field examinations performed with glaucoma program G1 were analyzed by 3 perimetrists. The task consisted of defining the existence of clusters or scotomas. Considerable discrepancy with regard to the existence or the size of clusters and/or scotomas was found among the three perimetrists. The median difference in number of clusters as compared for each pair of interpreters was found to differ from zero at a significance level of 5% (Wilcoxon's signed-rank nonparametric test). These findings suggest that the interpretation of a visual field status by human observers will always remain subjective and to a large extent contradictory. This situation calls for the implementation of interpretative computer software to supplement the currently available algorithms. PMID- 8485447 TI - Oral clonidine premedication prevents the rise in intraocular pressure following succinylcholine administration. AB - The objective of the study was to assess the effects of premedication with clonidine on intraocular pressure (IOP) after the administration of succinylcholine. Fifty elderly patients undergoing ophthalmic surgery were randomly allocated to two study groups. Group 1 patients (n = 25) received clonidine, 300 micrograms p.o. In group 2 (n = 25), the benzodiazepine dipotassium clorazepate was given p.o. at a dose of 0.3 mg.kg-1. Anesthesia was induced with thiopental 3-4 mg.kg-1, alfentanil 10 micrograms.kg-1, atracurium 0.07 mg.kg-1, and succinylcholine 1 mg.kg-1. Nine IOP measurements were taken in each patient starting before premedication and ending 3 min after endotracheal intubation. In both groups, there was a decrease in IOP after induction of anesthesia with thiopental and alfentanil. Succinylcholine administration and endotracheal intubation had no further effect on IOP in the clonidine group. In group 2, succinylcholine caused an increase in IOP when compared with the post induction value. We conclude that clonidine premedication can prevent the increase in IOP following succinylcholine administration. PMID- 8485448 TI - How is protein kinase C activated in CNS. AB - Protein kinase C (PKC) enzyme family consists of the Ca(2+)-dependent and independent subgroups of phospholipid/diacylglycerol (DAG)-stimulated serine/threonine protein kinases. These enzymes exhibit distinct cellular and subcellular localizations in CNS and subtle differences in their biochemical characteristics and substrate specificities. It is believed that each of these isoenzymes respond differently to different input signals. However, detailed mechanism for the functioning of these enzymes in vivo is largely unknown; this is in part due to the absence of specific activator, inhibitor, or substrate for each of these enzymes. Recent advances in biochemical, biophysical, and molecular characterizations have defined certain structural features important to confer the stimulatory responses of these enzymes to Ca2+, DAG or phorbol ester, and Zn2+; other features important for the binding of anionic phospholipids, Ca2+/phospholipid complexes, and cis-unsaturated fatty acids have not yet been characterized. Activation of PKC requires the increase in [Ca2+]i and DAG and/or cis-unsaturated fatty acids. Ca2+ promotes the interactions of the Ca(2+) dependent subgroup of PKCs with membrane phosphatidylserine (PS) and the enzymes become partially active when simultaneously associated with phosphatidylinositol 4,5-bisphosphate or fully active when DAG is available. Free fatty acids such as arachidonic acid, generated by the activation of phospholipase A2, could synergize with DAG to activate the enzyme maximally. The Ca(2+)-independent subgroup of PKCs also become active when associated with PS at elevated level of DAG. Sustained activation of PKCs leads to the conversion of these enzymes into membrane-inserted and membrane protein-associated forms, which may be responsible for certain long-term neural responses. Activation of PKC results in the phosphorylation of cellular proteins; among them, several calmodulin (CaM) binding proteins are the prominent substrates of these kinases. Phosphorylation of these proteins by PKC favors the release of CaM, which is required for the Ca2+/CaM-dependent enzymes. Thus, activation of PKCs can lead to diverse cellular responses through such amplification steps. Future studies should be directed at the elucidation of the activation of each PKC isoform in vivo to correlate with the physiological responses. PMID- 8485449 TI - Cytokines in neuronal cell types. AB - Cytokines are signals in the immune system, and may have effects on cells distant from the cells of origin. These proteins have been suggested as messengers in the communication between the immune system and the nervous system, in which signals travel only short distances. Neuroimmune interactions have been discussed in view of findings that nervous signals are important for the immune response. The occurrence of neurotransmitter receptors on lymphocytes and cytokine receptors on nerve cells or glia has initiated further studies e.g. on the localization of different cytokines in the nervous system and on long and short term actions of cytokines in the nervous system. Interleukin-1 has been studied extensively along these lines, and found to occur in the nervous and endocrine system, for example in the adrenal chromaffin cells, and to have effects such as induction of slow wave sleep and stimulation of adrenocortical and gonadotropic hormones. Other cytokines implicated as signals in neuroimmune interactions are IL-2, IL-6, IFN gamma and TNF-alpha. The functional studies suggest the occurrence of cytokine receptors in the brain, and experiments using 125iodine-labelled IL-1 alpha demonstrate differential distribution of binding sites in the mouse brain. Recently, evidence emerged of an endogenous receptor antagonist for IL-1, which may prove useful for the understanding of the mechanisms of IL-1's actions in the nervous system. A role for cytokines in regulation of the immune response but also in adjusting the organism to the host reaction is implicated. Furthermore, several findings indicate their role as growth promoting factors, and for example the induction of NGF production by IL-1 suggests involvement of this cytokine in regeneration and development in the nervous system. The significance of neuronally produced cytokines may be based upon the anatomically distinct releasing sites that the specific synaptic organization of the nervous system offer and future studies should determine whether cytokines act as neurotransmitters. PMID- 8485450 TI - Two cytosolic puromycin-sensitive aminopeptidase isozymes in chicken brain: molecular homology to brain-specific 14-3-3 protein. AB - Two puromycin-sensitive aminopeptidase isozymes (PSA-I and PSA-II) were isolated from chicken brain cytosol by ammonium sulfate fractionation followed by column chromatography on Cellex D and AH-Sepharose 4B and separated on Bio-Gel HTP. Each was purified to homogeneity on Sephadex G-200, Arg-Tyr-AH-Sepharose, Bio-Gel HTP, and preparative gel electrophoresis. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, PSA-I appeared to be a monomer with a molecular mass of 105 kDa, and PSA-II to be composed of two subunits of 25 kDa and 100 kDa. The tryptic maps of 100 kDa and 105 kDa protein in HPLC are different in peak frequency, height, and composition. The internal peptide sequence of PSA-I has a considerable homology to PSA-II. Both isozymes have repeated copies of common peptide segments and have no significant sequence homology to other peptidases and proteinases. These thio and Co(2+)-activated isozymes have a neutral pH optimum and are inhibited by puromycin and bestatin. PSA-II is more sensitive to trypsin and heat treatment, has a lower Km to Met-enkephalin, and is more active on Arg BNA and Pro BNA. Our results suggest that PSA-I and PSA-II derive from translation of two RNAs of a new gene family related to the brain-specific 14-3-3 protein. PMID- 8485451 TI - Characterization of [3H]staurosporine binding in protein kinase C-II purified from rat brain. AB - The type II protein kinase C (PKC-II) densely present in mammalian brain plays functional roles in CNS. We examined the characteristics of [3H]staurosporine binding to PKC-II purified from rat brain, compared to [3H]phorbol 12, 13 dibutyrate (PDBu) binding. In brief, [3H]staurosporine binding increased by phosphatidylserine (PtdSer) in a concentration-dependent manner and the binding was enhanced by Ca2+ and phorbol 12-myristate 13-acetate (PMA). In the presence of Ca2+, PMA and PtdSer, Bmax of these bindings markedly increased, but KD did not change. These characteristics of binding were similar to [3H]PDBu binding to PKC-II. Although [3H]PDBu binding was not affected by protein kinase inhibitors such as staurosporine, H-7, K-252a and K-252b, [3H]staurosporine binding was inhibited by these inhibitors. [3H]staurosporine binding was inhibited by several ATP analogues, but was not by guanine nucleotides. PtdSer-induced increase in [3H]PDBu binding was inhibited by Zn2+, but Zn2+ induced increase in [3H]staurosporine binding as well as PtdSer and/or Ca2+. Staurosporine would thus appear to bind to a domain different from phorbol ester-binding one in PKC, interactions between both domains may regulate kinase activity, and 1 mol staurosporine and 4 mol phorbol ester may bind to 1 mol PKC-II. PMID- 8485452 TI - Sulfation of proteins in the primate cerebellum and young rat brain. AB - Protein tyrosine sulfotransferase activity in a 20,000 g sedimentable fraction of monkey cerebellum was demonstrated. Both endogenous proteins and the exogenous substrate poly (Glu, Ala, Tyr) random copolymer were sulfated. The copolymer in the low molecular mass range (approx 20 kDa) was preferentially sulfated. Addition of copolymer inhibited sulfation of endogenous proteins. Mg2+ and Mn2+ promoted sulfation. 35S-Labeled proteins from monkey cerebellum and young (10 days old) rat brain were subjected to lectin-Sepharose chromatography to identify the presence of sulfated glyco-proteins. Labeled proteins from both these sources could bind and get eluted from Concanavalin A-Sepharose and Ricinus Communis agglutinin-Sepharose column suggesting the presence of mannose or galactose containing glycosulfoproteins. PMID- 8485453 TI - Is there a significant somatodendritic uptake of dopamine in the substantia nigra? Evidence from the weaver mutant mouse. AB - Slices of the substantia nigra from normal mice and from mice with the weaver gene were used to study somatodendritic uptake of dopamine. The substantia nigra of the homozygous weaver mouse is deficient in both cell bodies and dendrites whereas the substantia nigra of the heterozygous weaver mouse is deficient only in dendrites. Accumulation of [3H]dopamine by nigral slices obtained from each genotype was not different from that observed in slices obtained from control mice. The observed accumulation of [3H]dopamine was apparently taking place predominantly into serotonergic and noradrenergic elements since significant reductions were obtained by both fluoxetine and desipramine at concentrations that were selective for the serotonin and norepinephrine carriers, respectively. In the absence, as well as in the presence of fluoxetine and desipramine, dopamine accumulation in the substantia nigra was only slightly attenuated by the known dopamine uptake blocker GBR 12909. These data argue against a significant presence of somatodendritic uptake systems for dopamine in the substantia nigra and suggest that caution be used in the interpretation of results from studies on dopamine release from nigral slices when [3H]dopamine has been used to preload the tissue. Under such experimental conditions, it is likely that a large proportion of the released tritium might come from neurons other than those which contain endogenous neurotransmitter dopamine. PMID- 8485454 TI - Partial restoration of choline acetyltransferase activities in aging and AF64A lesioned rat brains by vitamin E. AB - It has been suggested that the activity of the enzyme responsible for the synthesis of acetylcholine, choline acetyltransferase (ChAT), is substantially reduced in the neocortex and hippocampus of Alzheimer's and other aging brains. d alpha-Tocopherol (vitamin E), a free radical scavenger fat-soluble vitamin, was utilized in the present study to determine whether its supplementation in aging and ethylcholine mustard aziridinium (AF64A)-lesioned rats would improve the cholinergic hypofunction. Vitamin E (given 24 h and 15 min prior to AF64A administration) significantly (P < 0.01) reversed the effect of AF64A in hippocampal choline acetyltransferase activity, but it did not cause any change of this enzyme activity in other brain regions (striatum and frontal cortex), nor did it cause any significant change after 30-day daily treatment in AF64A lesioned rats. Furthermore, vitamin E (50 mg/kg, i.p. for 30-day treatment) significantly (P < 0.01) partially restored the enzyme activity in striatum of aging (20-28 month old) rats. The present result indicates that vitamin E can partly restore the hypofunction of the cholinergic system in aging and partly prevent the toxicity in AF64A-lesioned rats. PMID- 8485455 TI - Concentrations of noradrenaline at neuronal uptake sites during sympathetic nervous inhibition and activation in rabbits. AB - Concentrations of noradrenaline at peripheral neuronal uptake sites were examined during sustained changes in sympathetic nervous activity produced by intracisternal infusion of yohimbine or clonidine in conscious rabbits. The gradient between concentrations of noradrenaline in plasma and at neuronal uptake sites was estimated by comparing the formation of the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), from intravenously infused and endogenously released noradrenaline. At resting levels of sympathetic activity the noradrenaline concentration at neuronal uptake sites (4.2 +/- 0.5 nmol/l) was 3.4-fold greater than the concentration in arterial plasma (1.3 +/- 0.1 nmol/l). Noradrenaline at neuronal uptake sites increased to 9.4 +/- 1.3 nmol/l after yohimbine and decreased to 2.4 +/- 0.1 nmol/l after clonidine. The noradrenaline concentration gradient was not altered by intracisternal infusion of yohimbine or clonidine. Thus, a positive linear relationship (r = 0.97) was observed between concentrations of noradrenaline at neuronal uptake sites and in plasma. The gradient was positively related to the efficiency of noradrenaline reuptake (r = 0.81). The results show that arterial plasma concentrations of noradrenaline are considerably less than concentrations close to sites of release, but accurately reflect changes in amounts of noradrenaline at release sites during sustained changes in sympathetic activity. The gradient in noradrenaline concentrations between neuronal uptake sites and plasma is largely dependent on the efficiency of neuronal reuptake. Since the gradient is not altered by sympathetic nervous inhibition or activation, the proportion of noradrenaline removed by neuronal and extraneuronal uptake does not appear to be altered by moderate changes in transmitter release. PMID- 8485456 TI - Retroviral-mediated gene transfer of the porcine choline acetyltransferase: a model to study the synthesis and secretion of acetylcholine in mammalian cells. AB - We have constructed a recombinant retrovirus that expresses choline acetyltransferase (ChAT) by placing the porcine enzyme cDNA under the control of the 5' long terminal repeat of the retroviral vector pMMuLV. Using retrovirus mediated gene transfer, we have expressed ChAT in astroglial (STR-SVLT) and neuroendocrine (RIN) cell lines. Both genetically modified cell types synthesize acetylcholine (ACh). ACh is also present in the culture medium at a low concentration relative to that found in the modified cells. This result suggests that the synthesized ACh is retained within the cells and released by these two cell types. Release of ACh is not increased in the presence of the calcium ionophore A23187 or by depolarizing concentrations of potassium in either STR SVLT or in RIN cells. The implications of these studies for understanding ACh release mechanisms are discussed. PMID- 8485457 TI - Occurrence of heterogeneity of N-linked oligosaccharides attached to sycamore (Acer pseudoplatanus L.) laccase after excretion. AB - The N-linked oligosaccharide moieties of sycamore (Acer pseudoplatanus L.) laccase are known to be highly heterogeneous. We confirmed that this oligosaccharide heterogeneity was caused not only during the oligosaccharide biosynthesis in Golgi apparatus, but also after the excretion of laccase protein into a culture medium. The culture medium for the sycamore cells (Acer pseudoplatanus L.) contained beta-galactosidase, alpha-L-fucosidase, beta-N acetylglucosaminidase, alpha-mannosidase and beta-xylosidase activities. We showed that the largest sugar chain in laccase, oligosaccharide F, [formula: see text] was degraded to [formula: see text] by a crude exoglycosidase mixture in the culture medium. PMID- 8485458 TI - Changes in translatable mRNA populations induced in rice seedlings by exposure to freeze-thaw stress. AB - In order to examine whether changes in gene expression are induced by injury in seedlings of rice (Oryza sativa) after a lethal freeze-thaw stress. mRNAs were extracted and their in vitro translation products were compared with those of the control plants by polyacrylamide gel electrophoresis. An mRNA encoding an entirely new protein with M(r) of ca. 37 kDa was detected as early as 30 min of thawing at 28 degrees C. Two-dimensional gel electrophoresis revealed the induction of mRNAs for at least 10 additional proteins, including those in a range of 15 to 20 kDa. Most of these proteins appear to be distinct from heat shock proteins. The steady state level of mRNAs encoding putative major light harvesting chlorophyll a/b binding protein-I and -II were, on the other hand, very low as compared with those of the control plants. The changes observed resemble those previously seen in cold-sensitive plants exposed to sub-lethal chilling temperatures (4-10 degrees C). PMID- 8485459 TI - Cold stability of microtubules of Mimosa pudica. AB - The unique property of Mimosa pudica microtubules is that they are cold stable in nature. They do not dissociate at 0 degrees C unlike animal microtubules. No other protein fractions of M. pudica are responsible for the cold-resistance property of these microtubules. It seems that tubulin, itself, has an intrinsic cold resistance which makes it unique compared with animal tubulin. Moreover, M. pudica microtubule makes cold-sensitive goat brain microtubule cold-resistant when used in greater than the suboptimal concentration. PMID- 8485460 TI - Integration of porin into the outer mitochondrial membrane through the common import machinery located in contact sites. AB - Although no binding of porin-precursor to trypsin-pretreated rat liver mitochondria was detectable, its integration into these mitochondria was observed to some extent, possibly by the bypass-import system first demonstrated in fungus mitochondria. A topographical study of this bypass-import system demonstrated that import of porin occurs at contact sites between the outer and inner membranes. Furthermore, antibodies to 29 kDa outer membrane protein, a component of the import machinery in contact sites for precursors of ornithine aminotransferase and sulfite oxidase, inhibited the integration of porin, suggesting that the 29 kDa protein is involved in the imports of most mitochondrial precursor proteins. PMID- 8485461 TI - Status of tryptophan residue in cobrotoxin and alpha-bungarotoxin. AB - Acrylamide quenching studies indicated that the exposure degree of the Trp residue in cobrotoxin was higher than that in alpha-bungarotoxin. The Trp residue of cobrotoxin was in a positively charged environment as revealed by iodide quenching, while the Trp residue of alpha-bungarotoxin was not accessible for iodide. Analysis of hydrophilicity profile and local concentration of positively charged residues of toxin molecule also indicated that Trp in cobrotoxin was in a highly hydrophilic and positively charged environment. Measurement of Trp fluorescence with increasing temperature showed that the stability of environment of Trp in alpha-bungarotoxin was higher than in cobrotoxin. Result of competitive binding for nicotinic acetylcholine receptor (AchR) between cobrotoxin and alpha bungarotoxin revealed that the molecular interaction of the two toxins with AchR was not the same. These, together with the fact that the cationic groups of the two toxins are involved in the binding with AchR, suggest that the observed different environment surrounded Trp residue and different AchR binding mechanism might fulfill a different requirement of the invariant Trp in the lethality of cobrotoxin and alpha-bungarotoxin. PMID- 8485462 TI - Nitecapone protects the Langendorff perfused heart against ischemia-reperfusion injury. AB - We assessed the protection afforded against myocardial ischemia/reperfusion by nitecapone in the Langendorff heart model using male Sprague-Dawley rats. We found that when present in the perfusate 10 microM nitecapone improved the mechanical function of the heart and lowered the enzyme leakage of lactate dehydrogenase after 40 minutes of global ischemia. In nitecapone treated hearts the content of oxidized proteins and lipids (carbonyl groups and endogenous lipid fluorescent products) decreased. Nitecapone partially prevented the loss of total sulfhydryl groups and vitamin E after ischemia and reperfusion. We suggest that the mechanism of nitecapone protection most likely involves direct antioxidant action and enhancing the activity of other antioxidants. PMID- 8485463 TI - Base specificity and binding of anti-ss/dsDNA monoclonal antibody. Application to the determination of ssDNA. AB - An anti-DNA murine hybridoma was generated and selected in a fusion of Sp2/0 myeloma cells with splenocytes derived from BALB/c mice immunized with DNA/protein complex. The monoclonal antibody designated as 4C7 was assessed by competitive immunoassay for binding to denatured, structurally single-stranded (ss)DNA, double-stranded (ds)DNA and oligodeoxynucleotides. The monoclonal antibody exhibited a marked preference for the ss conformation. Competitive inhibition assay performed with nucleosides and homopolynucleotides indicated that the deoxyadenosine residue was essential for antibody recognition and binding. The monoclonal antibody was purified by poly(A)-Sepharose chromatography and biotinylated. The ssDNA detection limit in the enzyme-linked immunosorbent assay with the biotinylated antibody ranged from 1 to 16 ng/ml. A dot immunobinding test was developed which was sensitive for the quantitation of picogram amounts of single-stranded DNA deposited on nitrocellulose filters and applied to the immunoenzymatic detection in human sera of target DNA. PMID- 8485464 TI - Preferential stimulation by D-glucose of oxidative glycolysis in pancreatic islets: comparison between B and non-B cells. AB - In purified pancreatic islet B cells, a rise in D-glucose concentration from 2.8 to 16.7 mM increased the production of both 14CO2 from D-[3,4-14C]glucose and 3HOH from D-[5-3H]glucose to a much greater relative extent than in purified non B islet cells. Moreover, the paired ratio between D-[3,4-14C]glucose oxidation and D-[5-3H]glucose utilization was significantly increased, as a result of the rise in hexose concentration, in purified B cells, but not so in purified non-B cells. It is proposed, therefore, that a preferential stimulation by D-glucose of oxidative relative to total glycolysis represents an intrinsic attribute of insulin-producing cells, as distinct from other endocrine islet cells. PMID- 8485465 TI - Opposite response to starvation of Trp/LNAA ratio in lean and obese Zucker rats. AB - Total blood and plasma free amino acids and plasma urea levels were studied in fed and 24 h fasted Zucker rats. In fed animals there were no differences between obese and lean rats in the overall essential and non essential blood free amino acids. However, starvation reduced blood amino acid levels in the obese animals compared to the lean group, mainly due to changes in the plasma compartment. The reduction of available amino acids from plasma in the obese rats during starvation affected most of the amino acids, including the branched chain amino acids, which showed higher levels in the fed situation than in lean rats. Of particular interest is the opposite response to starvation in lean and obese Zucker rats concerning the plasma ratio of tryptophan (Trp) to the large neutral amino acids (LNAA) which could be implicated in the alteration of food intake and energy expenditure characteristic of obesity. PMID- 8485466 TI - Steroid induced single strand breaks in DNA mediated by active oxygen species and its biological consequences. AB - A mutagenic steroidal derivative (3 beta-Acetoxy-5 alpha-Cholestano[6 alpha,5 d']1'-3'oxathiolane-2' thione) structurally related to cholesterol caused strand scission and induced nicks in calf thymus, supercoiled pBR322 and single stranded M13 mp8 phage DNAs. S1 nuclease hydrolysis, reaction with pBR322 and M13 phage DNA as well as treatment of E. coil mutant strains and phage was used to evaluate the effect of test steroid on the DNA molecule. The strand scission/nicking of DNA by the test steroid was enhanced by some metal ions, especially the Cu(II). Scavengers of active oxygen radical species significantly inhibited the S1 nuclease hydrolysis by the test steroid indicating the major role of active oxygen species in DNA strand scission and nicking. The steroid brought about the DNA degradation even in the absence of S1 nuclease. There was an appreciable reduction in the survival of steroid treated polA and lig mutants of E. coli K12 compared to the wild type strain. Phage on steroid treatment also lost its plaque forming units (P.F.U.) which was more pronounced in the polA and rec A background. PMID- 8485467 TI - Local anaesthetic effects on trophoblast membrane fluidity. AB - Previous studies showed that anaesthesia with the barbiturate Thiopental induces an increase in membrane fluidity and a decrease in acetylcholinesterase activity in syncytiotrophoblast plasma membranes (SPM) obtained from placentas after Cesarean section. The aim of the present work was to compare the effect of a local anaesthetic (bupivacaine hydrochloride, trade name Marcaine) on SPM in vivo and to establish whether the anaesthetic is still present in the membrane after tissue preparation. The acetylcholinesterase activity was lower in Marcaine anaesthetized SPM (27 +/- 3 against 39 +/- 6 in the control). The Marcaine action on the SPM can be ascribed to a competitive inhibition, similar to that reported for Thiopental. Fluorescence studies of the order parameter P showed it to be higher in SPM obtained from control (0.253 +/- 0.012) than in SPM obtained from Marcaine-exposed membranes (0.240 +/- 0.015). The local anaesthetic is still present in the SPM after their preparation (20.1 ng per mg membrane protein). It appears that the local anaesthetic exhibits an effect similar to that of the general anaesthetic, apparently due to binding to the membrane. PMID- 8485468 TI - Lipid peroxidation on dialysis membranes. AB - The aim of this study was to compare the changes of lipid peroxidation during haemodialysis (HD), using various types of dialyser membranes. A significantly higher concentration of total and free TBARS (thiobarbituric acid reacting substance) was found in blood and in plasma of HD patients, compared with the control group of blood donors. During the HD session the TBARS levels grow significantly, compared to the initial levels on both membranes (Alpha 500, Pro500), and are significantly higher after 15 min of HD on Alpha 500 membrane. The levels of TBARS appear to be significantly higher in patients on regular HD treatment, which may be due to a more intensive lipid peroxidation. There were significant acute changes in lipid peroxidation during one HD session. The changes in lipid peroxidation differ with the use of various HD membranes. PMID- 8485469 TI - B-->Z transition in native calf thymus DNA depends on its microenvironment. AB - Z-DNA forming potentiality of native calf thymus DNA was investigated under varying experimental conditions. Ethidium intercalation and Scatchard analysis data showed decreased binding of ethidium to nDNA at 4.27 M NaCl. A comparison of ethidium binding to DNA in low and high salt indicated the formation of Z-DNA. The binding of monoclonal anti-Z-DNA antibody to nDNA fragments brominated in high salt reiterated the transition of B-->Z conformation. PMID- 8485470 TI - The major fat-globule membrane proteins, bovine components 15/16 and guinea-pig GP 55, are homologous to MGF-E8, a murine glycoprotein containing epidermal growth factor-like and factor V/VIII-like sequences. AB - The glycoproteins, Components 15/16 and GP 55, were partially purified from bovine and guinea-pig fat-globule membrane (FGM), respectively. Peptides prepared from immunoblots of Component 16 and GP 55, were shown by sequencing, to be similar to mouse MFG-E8 and a human milk protein of M(r) 46,000. Both of these latter proteins are associated with the FGM and contain epidermal growth factor like domains and/or factor V/VIII-like sequences. These data complement earlier biochemical studies on the biosynthesis, tissue distribution and topology of Components 15/16 and GP 55, and indicate that MFG-E8-like proteins are expressed on the apical surfaces of mammary epithelial cells and are secreted both in a soluble form and as major components of the FGM in diverse species. The possible function of these proteins in lactation and in mammary and neonatal development is discussed. PMID- 8485471 TI - Calcium binding site mutants of calmodulin adopt abnormal conformations in complexes with model target peptides. AB - We have examined the ability of two series of calcium binding site mutants of Drosophila calmodulin to form complexes with the model target peptides melittin and mastoparan. Unlike the wild-type complex, the 1:1 protein:melittin complexes formed by mutants of the C-terminal sites are unable to bind a second molecule of melittin. In contrast, a site 2 mutant shows increased ability to bind two molecules of melittin. For the shorter peptide mastoparan, most mutants form aberrant complexes that are best interpreted in terms of a model in which mastoparan interacts with both terminal domains of calmodulin. For two of the target enzymes of calmodulin, the three mutants which form mastoparan complexes most similar to the wild-type complex are also the best enzyme activators. PMID- 8485472 TI - Two interconvertible forms of glucose-6-phosphate isomerase in rat muscle. AB - Chromatography of crude rat muscle extracts on CM-cellulose resulted in separation of glucose-6-phosphate isomerase (GPI) into two active peaks (designated types I and II in order of elution). Incubation of type I and type II at pH 6.0, 7.0, or 8.0 in the presence and absence of KCI revealed that one type of GPI is converted to the other type under certain conditions and that the two types are interconvertible by changing the incubation conditions. The two types were similar in molecular weight, kinetic property, and optimum pH. A remarkable difference was observed in pH-activity profile: the activity of type I, but not type II, was detectable at pH 6-7. The present results suggest that rat muscle has two types of GPI which are interconvertible and that the two types may be conformational variants of the same enzyme. It is conceivable that the interconversion between the two types is related to the regulation of glycolysis at lower intracellular pHs. PMID- 8485473 TI - Sickle cell disease: the transplant issue. AB - A legal moot (mock trial) was held in London in the Middle Temple Hall on Saturday 31 October 1992 to debate the place of BMT in sickle cell disease. The exact wording of the motion, which allowed a very full discussion to take place, was as follows: Bone marrow transplantation should forthwith be offered to all children in the UK with symptomatic sickle cell anaemia who have HLA compatible siblings. PMID- 8485474 TI - Microbial carriage, sepsis, infection and acute GVHD in the first 25 BMT at the Royal Liverpool Children's Hospital. AB - The first 25 BMTs at the Royal Liverpool Children's Hospital (Alder Hey) were performed between April 1987 and July 1991. The aim of this report is to evaluate selective decontamination of the digestive tract (SDD) during the first post-BMT month in this series of 14 allografts and 11 autografts. SDD is a method used to abolish carriage of potentially pathogenic microorganisms including yeasts, Staphylococcus aureus and Gram-negative bacilli (GNB). Chlorhexidine mouth wash was used to decontaminate the oropharynx, and neomycin, colistin (polymyxin E) and nystatin (NEOCON) were given to eradicate gut carriage. Oropharyngeal decontamination was successful in 48% of patients, gut carriage was abolished in 60%, and eradication of the carrier state at both sites was achieved in 33%. A septic response was seen in 76% of children and 36% developed septicaemia (indigenous Gram-positive cocci only). A low carriage index for the target microorganisms during the study manoeuvre of SDD was associated with negative blood cultures (p < 0.01). Acute GVHD occurred in 28% of allografts, but was seen in none of the successfully decontaminated children (p < 0.05). It is concluded that septicaemia from yeasts and GNB, but not the septic response, were successfully prevented by SDD. PMID- 8485475 TI - Detection of residual host cells after bone marrow transplantation using non isotopic in situ hybridization and karyotype analysis. AB - Karyotype analysis and interphase cytogenetics by means of non-radioactive in situ hybridization (NISH) with Y and X-specific probes were used to detect residual host cells in BM of 18 male patients who had received a BMT from their sisters. All patients but one had a malignant blood disease; 17 patients were clinically in continuous remission at the time of the investigations and throughout the follow-up period. No host cells were detected by karyotype analysis in patients who were in clinical remission. NISH with a biotinylated Y specific probe showed residual host cells in 16 of the 17 patients in clinical remission. In samples from three patients the existence of host cells was further confirmed by revealing the XY-containing cells with two-color fluorescence in situ hybridization (FISH) using X- and Y-specific probes on direct BM smears showed > 3% residual host cells in 50% of the samples studied at or later than 2 months post-BMT. On conventional cytogenetic preparations < 1% Y-specific cells were detected in all but two samples at > or = 2 months post-BMT. There was no difference in the proportion of host cells between patients conditioned with total body irradiation and CY and those who received busulphan and CY. The recipient's stromal or epithelial cells in the aspirates probably account for most of the host cells detected. In conclusion, small numbers of residual host cells detected by interphase cytogenetics with a Y-specific probe do not indicate an imminent relapse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485476 TI - Dynamics of erythropoietic recovery following bone marrow transplantation: role of marrow proliferative capacity and erythropoietin production in autologous versus allogeneic transplants. AB - The mechanisms of erythrocyte recovery after BMT are not known. We investigated the respective role of marrow function and erythropoietin production in 31 ABMT and 47 allogeneic BMT by analysing peripheral counts, serum erythropoietin levels, and serum transferrin receptor (TfR) levels which have been shown to be a quantitative measurement of erythropoiesis. Median times to complete neutrophil (25 vs 48 days, p < 0.0001) and platelet (45 vs 263 days, p < 0.001) recovery were faster after allogeneic BMT than ABMT, but complete erythrocyte recovery was slower (218 vs 101 days, p < 0.001). After ABMT, erythrocyte recovery paralleled that of neutrophils and platelets, and erythropoietin levels remained appropriate for the degree of anemia. After allogeneic BMT, erythrocytes developed independently of the other cell lines and defective erythropoietin production delayed recovery of adequate erythropoietic activity. This correlated with an alteration of renal function only in those patients remaining erythropoietin deficient beyond day 180. However, supranormal erythropoietin levels in interstitial pneumonia suggests that erythropoietin response to hypoxia is not abrogated. CMV infection could also affect erythropoiesis through erythropoietin production after ABMT as well as allogeneic BMT. It is concluded that after ABMT the development of erythropoiesis is determined by the overall marrow proliferative activity and erythropoietin plays only a facilitating role. After allogeneic BMT, erythropoiesis depends on erythropoietin levels which remain inadequate for prolonged periods of time. The results suggest that the administration of recombinant human erythropoietin could reduce transfusion requirements after BMT. PMID- 8485477 TI - Use of an anti-interleukin-2 receptor monoclonal antibody for GVHD prophylaxis in unrelated donor BMT. AB - Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results. PMID- 8485478 TI - Alterations in natural anticoagulant levels during allogeneic bone marrow transplantation: a prospective study in 27 patients. AB - The natural anticoagulants (antithrombin III, protein C, protein S), plasminogen and tissue plasminogen activator antigen (t-PA ag), were measured in 27 consecutive patients following allogeneic BMT. Thrombosis and veno-occlusive disease were not seen in this study. Changes in the levels of these proteins occurred mainly during acute GVHD. There were 14 patients who had no acute GVHD (group I) and 13 patients who had acute GVHD (group II). No changes in antithrombin III (ATIII), protein C, protein S and t-PA levels were found in group II before the appearance of acute GVHD when compared with group I. However, we noted a significant rise in protein S (p = 0.01), antithrombin III (p = 0.001) and t-PA ag (p = 0.0004) levels during acute GVHD. In contrast, protein C levels decreased early in GVHD (p = 0.005), and then increased progressively over the course of a month post-GVHD. No changes in plasminogen levels were observed. These results might reflect activation of and/or damage to endothelial cells during GVHD. PMID- 8485479 TI - Recovery after allogeneic marrow transplantation: prospective study of predictors of long-term physical and psychosocial functioning. AB - No prospective data have documented the physical and psychosocial functioning of patients before and after BMT. In this study 67 allogeneic transplant patients completed standardized self-report measures pre-transplant. Survivors were re assessed at 90 days (n = 34) and 1 year (n = 31) post-transplant. Telephone interviews established 4-year work history and performance status. Physical function was most impaired at 90 days post-transplant, with a return to pre transplant levels of functioning by 1 year in most areas. By 2 years post transplant, 68% of patients had returned to full-time work. Only 9% of 4-year survivors failed to return to full-time occupations. Mean levels of anxiety and depression did not change over the first year. Pre-transplant, 27% of patients reported depression and 41% reported elevated anxiety. Greater emotional distress at 1 year was predicted by pre-transplant family conflict, non-married status and development of less severe chronic GVHD. Impaired physical recovery at 1 year was predicted by more severe chronic GVHD, pre-transplant physical impairment and family conflict. The large majority of long-term survivors returned to full-time employment with normal physical and psychosocial functioning, although recovery took longer than 1 year for approximately 40%. Family relationships were important determinants of physical and emotional recovery. PMID- 8485480 TI - Delayed infusion of normal donor cells after MHC-matched bone marrow transplantation provides an antileukemia reaction without graft-versus-host disease. AB - When allogeneic BMT is used for the treatment of leukemia, depletion of T cells from the donor BM to avoid GVHD may be accompanied by persistence of host cells and post-transplant relapse. In this report, a murine model of MHC-compatible BMT was used to show that delayed infusion of immunocompetent donor cells early after T cell-deficient BMT eliminated residual host cells and provided an antileukemic effect without causing lethal GVHD. AKR (H-2k) recipient mice were pre conditioned with 9 Gy total body irradiation (LD50) and transplanted with 10(7) BM cells from MHC-matched B10.BR donors. These mice did not develop GVHD and became stable, long-term mixed (donor-host) T cell chimeras. In this model, mixed or incomplete donor T cell chimerism was associated with decreased GVL reactivity. AKR hosts that were transplanted with B10.BR bone marrow admixed with 3 x 10(7) B10.BR spleen cells (as a source of T cells) became complete donor T cell chimeras, but they developed severe and lethal GVHD. However, when the infusion of donor spleen cells was delayed until 21 days after BMT, few mice exhibited any clinical signs of GVHD, and > 95% of the mice became long-term survivors. The infused spleen cells eliminated residual host T cells by 21 days after infusion, and most chimeras were able to resist a supralethal challenge with AKR leukemia/lymphoma cells. Thus, post-transplant adoptive immunotherapy with normal mononuclear cells from the marrow donor may be an effective way to eliminate residual disease or treat leukemia relapse after BMT without causing significant GVHD. PMID- 8485481 TI - Disseminated subcutaneous Nocardia asteroides abscesses in a patient after bone marrow transplantation. AB - We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia asteroides in a 17-year-old female with AML undergoing allogeneic BMT. She was receiving immunosuppressive therapy with CYA and a corticosteroid for acute GVHD, and maintenance therapy with ganciclovir for interstitial pneumonia (IP) caused by CMV, but was not neutropenic. The subcutaneous abscesses spread from the primary infection on her right anterior leg to both thighs, the left buttock, both upper arms, the left forearm and right shoulder, indicating hematogenous dissemination. Nocardia asteroides was identified from biopsy material in culture. The patient was successfully treated with a combination of trimethoprim/sulfamethoxazole (TMP/SMX) and minocycline, given for 3 months. The possibility of nocardiosis should be considered in the differential diagnosis of such patients. PMID- 8485482 TI - Comparative study of intact A7 MoAb and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice. AB - Differences of pharmacokinetics and tumor imaging ability between intact monoclonal antibody A7 (A7 MoAb) and F(ab')2 fragments were studied in human colon cancer (LS-174T)-bearing nude mouse. First of all, we examined the yield and the immunoreactivity of F(ab')2 fragments after treatment with ficin as a function of time. The yield of F(ab')2 fragments reached about 50% after ficin treatment for 8 h, and the F(ab')2 retained about 80% of the immunoreactivity of the corresponding MoAb. Longer digestion with ficin produced smaller fragments (less than 92 kDa) with a lower yield and most of the immunoreactivity was lost. In pharmacokinetics studies, the F(ab')2 was preferentially taken up by the tumor, was cleared more rapidly from the blood circulation and seemed to have less non-specific tissue binding than intact A7 MoAb. In addition, the tumor image obtained at an early time using 131I-F(ab')2 was much superior in quality to that with intact 131I-A7 MoAb. The use of F(ab')2 fragments may be effective for tumor diagnosis and therapy. PMID- 8485483 TI - [11C] beta-CIT, a cocaine analogue. Preparation, autoradiography and preliminary PET investigations. AB - beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) is a cocaine analogue with a high affinity for the dopamine transporter. [11C] beta-CIT was prepared by N-methylation of nor-beta-CIT with [11C]methyl iodide. The total radiochemical yield of [11C] beta-CIT was 40-50% with an overall synthesis time of 35-40 min. The radiochemical purity was > 99% and the specific radioactivity at the time of injection was about 1000 Ci/mmol (37 GBq/mumol). Autoradiographic examination of [11C] beta-CIT binding in human brains post-mortem demonstrated a high level of specific binding in the striatum. PET examination of [11C] beta-CIT in a Cynomolgus monkey showed a marked accumulation of radioactivity in the striatum. The ratio of radioactivity in the striatum-to-cerebellum approached 5 after 87 min. In a displacement experiment, radioactivity in the striatum but not in the cerebellum, was markedly reduced after injection of unlabelled cocaine. [11C] beta-CIT has a potential as ligand for PET examination of cocaine effects in man. PMID- 8485484 TI - Biological activities of phthalocyanines--XV. Radiolabeling of the differently sulfonated 67Ga-phthalocyanines for photodynamic therapy and tumor imaging. AB - Phthalocyanines have been advanced as photosensitizers for the photodynamic therapy of cancer and selectively sulfonated derivatives have shown promise as tumor imaging agents. In order to study the effect of the degree of sulfonation on their biodistribution pattern, we prepared a series of sulfophthalocyanines (PcS) labeled with 67Ga. Direct chelation of metal free phthalocyanines with 67Ga gave chelates which demetallated on further purification whereas condensation of 67Ga with phthalic acid precursors, following purification and fractionation on Sep-Pak C18 cartridges, gave stable products. The distribution pattern of the [67Ga]GaPcS among human plasma proteins was strongly affected by the degree of sulfonation of the PcS. The lower sulfonated GaPcS showed significant binding to the various lipoprotein fractions whereas increased sulfonation favored association to albumin. The use of the 67Ga allowed for the validation of spectrophotometric quantification of GaPcS in biological samples and confirmed the in vivo stability of the radiolabeled complex. PMID- 8485485 TI - Synthesis, characterization and biodistribution of new 99mTc Oxo and nitrido complexes of unsaturated tetradentate (N2S2)ligands. AB - Three unsaturated Schiff base tetradentate (N2S2 or N2SO) ligands were synthesized and characterized. Oxo and nitrido 99m-technetium complexes were obtained with these ligands. The nitrido complexes were formed using a new easy method available as a kit. When injected into rats and mice, these lipophilic complexes were able to cross the blood-brain barrier but brain perfusion imaging could not be performed due to the insufficient uptake and retention time. PMID- 8485486 TI - Synthesis and in vivo evaluation of [18F]-N-(p-nitrobenzyl)spiperone ([18F]PNBS) in rats. AB - [18F]-N-(p-nitrobenzyl)spiperone, [18F]PNBS, was prepared and its in vivo uptake in rat brain was measured. A temporal increase in striatum:cerebellum ratio and frontal cortex:cerebellum (FC:Cb) ratio was observed. Blocking studies suggested the formation of a radiolabeled metabolite, presumably [18F]spiperone, that is capable of crossing the blood-brain barrier and labeling cortical 5-HT2 receptors. This was confirmed using the ISRP method of metabolite analysis indicating [18F]PNBS is not a suitable tracer for studying D2 receptors in vivo with PET. PMID- 8485487 TI - Preparation and biological characteristics of 99mTc-diol a renal agent. AB - The present work concerns the production of 1,2-dihydroxypropyl-1-phosphonic acid (diol) by acid hydrolysis of (-cis) 1,2-epoxypropylphosphonic acid (phosphomycin), and its formulation as a kit easily labeled with [99mTc]pertechnetate. Biodistribution studies and whole-body autoradiographies in mice show that 99mTc-diol has a specific affinity for the kidneys: it is rapidly cleared from the blood and excreted in urine (12.09 +/- 6.40% ID are excreted in urine at 5 min and 70.81 +/- 2.41% ID at 30 min post-injection). Part of the injected activity remains in the kidney cortex sufficiently long to permit kidney imaging (5.66 +/- 0.91% ID is still in kidneys 1 h post-injection). In comparison with other agents which also localize in the kidney cortex, such as 99mTc-DMSA and 99mTc-glucoheptonate (99mTc-GHA), the main differences are the following: the peak of renal activity is reached early in the 5 min post-injection period for 99mTc-diol, only at about 10 min post-injection for 99mTc-GHA and after 3 h post injection for 99mTc-DMSA. The uptake of 99mTc-diol by other organs, especially by bones, is much smaller than in the case of 99mTc-DMSA (1.25 +/- 0.11% ID of 99mTc diol compared to 11.31 +/- 1.17% ID of 99mTc-DMSA, 1 h post-injection). Unlike 99mTc-DMSA, the biodistribution of 99mTc-diol is not significantly influenced by acid-base imbalance, in addition, its renal uptake decreases in the presence of probenecid whereas its urinary excretion increases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485488 TI - Complexes of technetium-99m with phosphomycin, obtained by pH shifting: biological characteristics, whole-body autoradiography, gamma-camera study. AB - Phosphomycin (phos), a large spectrum antibiotic with preferential localization into the kidneys, can be labeled with technetium-99m at various pHs. However, the final pH in the labeling of phos by [99mTc]pertechnetate in the presence of SnCl2 seems to play a significant role in determining the biological properties of the final labeled product. Radiopharmacological characteristics of various forms of 99mTc-phos obtained at pHs 6.8, 4.5 and 2.5 were studied in mice, rats and rabbits. Significant differences in these products were shown by biodistribution studies in Balb/C mice and Wistar rats and confirmed by whole-body autoradiographies in mice and gamma-camera studies in rats and rabbits. 99mTc phos, pH 6.8, has a high uptake in kidneys from 2 min after injection (10.25 +/- 1.11 %ID) to 3 h after injection (8.26 +/- 0.42 %ID) and a rapid urinary excretion (19.9 +/- 7.35 %ID at 2 min after injection and 75.11 +/- 3.48 %ID at 3 h). Intrarenal pharmacokinetics studied by autoradiography showed a high concentration in the inner medulla and pelvis at 1 min after injection followed by an increased localization in kidney cortex, like 99mTc-DMSA. Preferential uptake in bones was shown by 99mTc-phos, pH 2.5, from 5 min to 3 h after injection (15.05 +/- 2.67 %ID at 3 h compared to 1.79 +/- 0.19 %ID of 99mTc-phos, pH 6.8, at the same time). A high urinary excretion of 99mTc-phos, pH 2.5, is shown as in the case of other bone agents (76.5 +/- 3.46 %ID at 3 h post injection) but without any kidney retention (1.80 +/- 0.26 %ID in kidneys 3 h post-injection).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485489 TI - Influence of fatty acid backdiffusion on compartmental analysis of external detection curves obtained with 123-iodohexadecenoic acid in isolated rat heart. AB - In isolated rat hearts, we investigated a possible backdiffusion of fatty acids and tried to determine whether it impaired our compartmental analysis of myocardial time-radioactivity curves obtained with an iodinated fatty acid, 16 iodo-9-hexadecenoic acid (IHA). Backdiffusion was not observed directly in the coronary effluents but was estimated by analysis of the external detection curves. Furthermore, when backdiffusion was not taken into account in the mathematical analysis, we obtained similar data on IHA intramyocardial metabolism. PMID- 8485490 TI - A simple method for affinity purification of radiolabeled monoclonal antibodies. AB - A simple method is described for affinity purification of radiolabeled antibodies using glutaraldehyde-fixed tumor target cells. The cell-bound antibody fraction is removed from the cells by an acid wash and then immediately subjected to buffer-exchange chromatography. The method was applied to the D3 murine monoclonal antibody which binds to a 290 kDa antigen on the surface of Line 10 guinea pig carcinoma cells. No alteration in the molecular size profile was detected after acid washing. Purification resulted in a significant increase in immunoreactivity by an average of 14 +/- 47% (SD; range 4-30%). PMID- 8485491 TI - Preparation, characterization and biological evaluation of cationic 99Tc/99mTc dioxime complexes. AB - New cationic 99Tc/99Tc complexes formed with various symmetrical and asymmetrical vicinal dioximes of different carbon chain length (C5-C8) were synthesized by reduction of pertechnetate with BH4-, separated by HPLC and characterized by i.r./u.v./vis. spectroscopy, FAB mass spectrometry and electrophoresis. All complexes studied are trisdioximes containing boron as a constituent. Their lipophilicity, as assessed by the octanol/saline partition coefficient, ranges over almost four orders of magnitude. The myocardial uptake of the 99mTc complexes in mice proves to be lower than expected. The organ distributions are distinctly affected by the lipophilicity, the position of the dioxime group and the introduction of a terminal methoxy group. PMID- 8485492 TI - Radioimmunoimaging of human breast carcinoma xenografts in nude mouse model with 111In-labeled new monoclonal antibody EBA-1 and F(ab')2 fragments. AB - Radioimmunoimaging characteristics of a new monoclonal antibody EBA-1 and its F(ab')2 fragments utilizing nu/nu mice bearing human breast carcinoma xenografts are described. 111In-DTPA conjugates of EBA-1 localized with tumor/blood ratios of 0.99 +/- 0.10 (P < 0.3) and 4.65 +/- 1.60 (P < 0.05), and localization indices of 1.25 and 2.61 at 24 and 72 h, respectively. A tumor/blood ratio as high as 28.86 +/- 6.90 (P < 0.025) was obtained with EBA-1 F(ab')2 radioconjugates at 48 h. These results suggest that EBA-1 and its F(ab')2 might be useful reagents in radioimmunoimaging and radioimmunotherapy. PMID- 8485493 TI - Simultaneous measurements of twenty-four-hour whole-body retention of 47Ca chloride and 99mTc-MDP: early differentiation of metabolic bone diseases in rat models. AB - The 24-h whole-body retention (24-h WBR) of 47Ca-chloride and 99mTc-MDP was measured in four rat models over a 6-week period at 2 week intervals. Fine detail bone radiographs of the femurs and histologic bone specimens were also obtained simultaneously. In the osteomalacic (M) and steroid-induced osteoporotic (S) groups the 24-h WBR values of 47Ca were significantly lower, and in the osteoporotic (P) group were higher than in the control (C) group from the second week. The 24-h WBR values of 99mTc-MDP were significantly higher in the M group and were lower in the S group from the second week. Simultaneous measurements of 24-h WBR of these two radiopharmaceuticals facilitated the early differentiation of metabolic bone diseases in the animal models prior to the detection of radiologic bone changes. PMID- 8485494 TI - Development and validation of a solvent extraction technique for determination of Cu-PTSM in blood. AB - The partitioning of [67Cu]Cu-PTSM between plasma and red blood cells (RBC) was investigated in vitro with human, rat, pig and dog blood. Significant inter species variability is observed in the plasma/RBC partitioning of tracer, ranging from c. 75% association with plasma in human blood to only c. 35% association with plasma in dog blood. This inter-species difference results from selective association of the [67Cu]Cu-PTSM tracer with human albumin. When [67Cu]Cu-PTSM is mixed with human blood in vitro at 37 degrees C the fraction of 67Cu radioactivity that remains plasma-associated decreases with time, apparently due to the expected intracellular decomposition of the Cu-PTSM complex by RBC; however, this process is sufficiently slow that it should have limited influence on [62Cu]CU-PTSM biodistribution following intravenous injection. Octanol extraction of blood was found to be an effective technique for quantitating the amount of intact [67Cu]Cu-PTSM complex in blood samples. When imaging with [62Cu]Cu-PTSM, octanol extraction may be useful for determining the [62Cu]Cu-PTSM content of arterial blood samples to establish a true radiotracer input function. PMID- 8485495 TI - Synthesis, receptor binding and tissue distribution of 17 alpha-E[125I]iodovinyl 11 beta-ethyl-estradiol. AB - In this study we prepared and evaluated a derivative of estradiol with an ethyl group at the 11 beta-position and an E-iodovinyl group at the 17 alpha-position. This new ligand binds to the estrogen receptor with an affinity slightly less than estradiol (RBA = 43%) at 0 degree C but much greater (RBA = 890%) at 25 degrees C. The 125I-labeled derivative was obtained by radioiododestannylation of the tri-n-butylstannyl precursor in good radiochemical yield with a specific activity exceeding 1500 Ci/mmol. The tissue distribution in immature female rats was evaluated over a 48 h period to determine uterine uptake and selectivity. Peak uterine uptake at 2 h was 6% ID/g and was significantly greater than that of [3H]estradiol, 2.4% ID/g. Substantial uptake in the uterus was still present at 48 h (2.4% ID/g). Co-administration of estradiol reduced the uptake at 2 and 24 h by 85%. Uterus-to-plasma ratios increased with time, from about 25:1 at 2 h to nearly 90:1 at 48 h. The affinity, ease of radiosynthesis and tissue distribution of the 17 alpha-E-[125I]iodovinyl-11 beta-ethyl-estradiol suggest that further evaluation of this agent as an imaging agent for estrogen-receptor-positive breast cancer is warranted. PMID- 8485496 TI - Evaluation of [11C]thymidine for measurement of cell proliferation in fast dividing tissues. AB - The purpose of this study was to investigate the possibility of using [11C]thymidine as a tumor marker for positron emission tomography studies. Biodistribution studies were set up to investigate the in vivo behavior of [11C]thymidine. Simultaneously, the DNA incorporation in fast dividing tissues and catabolism was studied. Our results confirm that [11C]thymidine can be used for detection of cell proliferation by positron emission tomography. As such, it can produce supplementary information in cancer research. PMID- 8485497 TI - Interaction of 99mTc-radiopharmaceuticals with transport proteins in human blood. PMID- 8485498 TI - Direct analysis of Kryptofix 2.2.2 in 18FDG by gas chromatography using a nitrogen-selective detector. PMID- 8485499 TI - A revised method for the synthesis of 1,1-bis(4-hydroxyphenyl)-2-phenylethylene (BHPE) and its derivatives. PMID- 8485500 TI - Comment on "An improved method of direct labeling monoclonal antibodies with 99mTc" by M. M. Alauddin, L. A. Khawli and A. L. Epstein, Nucl. Med. Biol. 19, 445-454. PMID- 8485501 TI - Development and registration of chiral drugs. AB - In this review we describe the impact of chirality on drug development and registration in the United States, Japan and the European Community. Enantiomers may have differences in their pharmacological profiles, and, therefore, chiral drugs ask for special analytical and pharmacological attention during their development. However, the registration authorities have no clear policy towards the registration of chiral drugs. The absence of a clear policy regarding chirality causes a great deal of confusion and frustration at various levels and is not in the interest of industries developing newer and more beneficial drugs. PMID- 8485502 TI - Generalized convulsive status epilepticus: pathophysiology and treatment. AB - The treatment of generalized convulsive status epilepticus according to a protocol, including a time schedule, prevents unnecessary delay and improves outcome. Based on a literature study and our own clinical experiences a treatment protocol is discussed with special emphasis on medical complications, choice of antiepileptic drugs, route of administration and a proper time schedule. PMID- 8485503 TI - Drug transport across the blood-brain barrier. III. Mechanisms and methods to improve drug delivery to the central nervous system. AB - This is the third part of a review on the transport of drugs across the blood brain barrier. In the first two parts, the anatomical and physiological aspects and the various techniques that can be used to study blood-brain transport have been discussed and reviewed. This third part focuses specifically on the mechanisms that are involved in drug transport across the blood-brain barrier. In addition, the opportunities to improve drug transport into the brain will be reviewed. Emphasis is on the transport of peptides. PMID- 8485504 TI - Evaluation of two prediction models for digoxin dosing. AB - The relationship between the digoxin elimination parameter (A%) and creatinine clearance (CLCr) was determined, from blood level data of 160 hospital patients receiving digoxin tablets. The linear regression equation obtained, which varied only slightly from that reported by Jelliffee previously, was used to predict serum digoxin concentrations in 140 patients of four age groups (50-60, 60-70, 70 80 and 80-90 years). The predictions made were found to be less biased and more precise, irrespective of the age of the patients, than those produced using another predictive method known as Dobbs method. However, correlation coefficients of predicted versus measured serum digoxin concentrations for each method did not differ significantly and frequency distribution analyses of prediction errors gave poor results (up to 63% only). Therefore, neither method can be considered to be superior to the other nor can they be said to ensure accurate predictions of serum digoxin concentrations. PMID- 8485505 TI - Stability of cisplatin in sodium chloride 0.9% intravenous solution related to the container's material. AB - The stability of cisplatin in sodium chloride 0.9% intravenous solutions contained in glass bottles, polyvinyl chloride bags, polyethylene and polypropylene containers was studied over two weeks. The solubility of cisplatin at 4 degrees C was also studied for possible precipitation. The type of container had no effect on cisplatin decomposition. No precipitation at 4 degrees C was observed within the time period studied. PMID- 8485506 TI - Biopharmacy and Pharmaceutical Technology Meeting. Oss, The Netherlands, 14 May 1993. Abstracts. PMID- 8485507 TI - Synthesis of [1-11C]D-glucosamine and evaluation of its in vivo distribution in rat with PET. AB - D-Glucosamine is a structural unit of many biologically interesting macromolecules. To investigate the feasibility of using labelled D-glucosamine as a tracer for anabolic processes, a two-step synthetic procedure for specifically labelling D-glucosamine in position 1 with carbon-11 was developed. [11C]Cyanide was reacted with an imine precursor, N-benzyl-D-arabinosylamine, to generate the [1-11]alpha-amino nitrile. Reduction to [1-11C]D-glucosamine was accomplished by catalytic hydrogenation using PdCl2 and the N-benzyl group was simultaneously removed. The total synthesis time from end-of-trapping of [11C]cyanide was 40-45 min and the decay-corrected radiochemical yield was 5-10% after HPLC isolation. The biodistribution of [1-11C]D-glucosamine in rat following i.v. bolus injection was investigated using positron emission tomography and showed that the availability of this substance for CNS anabolism is low with the primary limitation being the intact blood-brain barrier. PMID- 8485508 TI - A microcomputer-based whole-body counter for personnel routine monitoring. AB - The paper describes a cost-effective NaI(Tl) whole-body counter developed for routine examinations of worker intakes at an isotope production facility. Signal processing, data analysis and system operation are microcomputer-controlled for minimum human interactions. The pulse height analyzer is developed as an microcomputer add-on card for easy manipulation. The scheme for radionuclide analysis is aimed for fast running according to a knowledge base established from background samples and phantom experiments in conjunction with a multivariate regression analysis. Long-term stability and calibration with standards and in vivo measurements are reported. PMID- 8485509 TI - Structure-localization relationships of 11C-labeled phentermine derivatives: effect of aromatic substitution. AB - A series of phentermine analogs, including the unsubstituted, the para-F, -Cl, Br and -I, and the meta-CF3 derivatives, were labeled by [11C]methylation and evaluated in rats to determine the structure-localization relationships for this class of regional cerebral blood flow imaging agents. All the phentermines were well-localized in the brain; however, only the para-substituted agents were well retained. Localization in the nontarget tissue was affected by the lipophilicity of the substituent. Comparison with the radioiodinated analogs showed virtually identical results, which suggests that the compounds were not significantly metabolized. The agent with the best biodistribution characteristics was the N [11C]methyl-p-iodophentermine, with the p-bromo analog almost equivalent. PMID- 8485510 TI - Speech-language interventions in Alzheimer's disease. A functional communication approach. AB - Alzheimer's disease is a progressive degenerative neurogenic disease that is more prevalent among the old than the young. The primary symptoms are forgetfulness, repetitiousness, losing one's way, and the loss of ability to perform complex tasks on the job. Diagnostic confirmation of Alzheimer's disease is determined by autopsy. As of this writing, there is no specific drug that can stop or reverse the disease. Medical management is focused on treating behavioral symptoms and managing the individual's general well-being. The communication needs of the Alzheimer's client depend on the individual's level of cognition, degree of independence, circumstance, and communicative abilities. Due to their poor rehabilitation potential, the majority of persons with Alzheimer's disease are not suitable candidates for traditional therapy programs. An alternative to traditional therapies is the Tri-Model system. The Tri-Model philosophy of rehabilitation and service delivery systems (Glickstein and Neustadt, 1992) lends itself readily to the needs of the dementia client because the model is designed to maintain the continuum of rehabilitation care for individuals with "red flag" diagnoses such as dementia. Establishing a treatment protocol based on the Tri Model philosophy of rehabilitation not only assures the individual treatment based on his or her level of functional ability and rehabilitation need, it provides a framework for the rehabilitation specialist to use as reference for the various stages of disability and change during rehabilitation. The Tri-Model System is a decision tree which allows movement in any direction according to the client's needs (Figure 1). Clients, staff, and families are encouraged to set realistic goals at the outset of the rehabilitation program. By delineating three overlapping phases in the recovery process a base is established which allows the rehabilitation professional to appropriately follow the client after discharge and maintain the continuum of care. Since each restorative phase in the system requires the design of restorative programs which address that particular phase of the rehabilitation process and cooperation of an interdisciplinary team, addressing all three phases of rehabilitation at the time of the initial evaluation maintains the continuity of the client's treatment protocol throughout the course of the disease. Inclusion of Restorative III (functional maintenance) assures the continuum of care. The strength of the Tri-Model philosophy and system of rehabilitation is the inclusion of the definition and delineation of functional maintenance, the most neglected and for many clients the most important part of a complete rehabilitation program. When an incomplete definition of rehabilitation is used, questions regarding the efficacy of treatment is common.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8485511 TI - Consultation and collaboration programs for individuals with autism. AB - Students with autism present a challenge to the SLP not only because of the severity of their communication disorders, but also because of the great variety of learning styles and social skills. Collaboration- and consultation-based service delivery systems offer an alternative to traditional therapy for these students. This model uses the strength of a team approach and permits strategies for improving communication that are not possible in other environments. PMID- 8485512 TI - Structural features critical to the activity of an ecdysone receptor binding site. AB - Two ecdysone-response elements from the hsp27 (hsp27 EcRE) and the Fbp1 (D EcRE) genes of Drosophila melanogaster were used as probes in a gel shift assay to investigate the interactions of the ecdysone receptor (EcR) with its cognate DNA response element. The source of EcR was a nuclear extract from the late third larval instar fat body. The hsp27 and D EcREs share a sequence similarity at 12 positions over a 15bp region including an imperfect palindromic structure consisting of two pentamer half-sites separated by a single intervening nucleotide. We have shown that a short oligonucleotide containing this 11bp imperfect palindrome of the hsp27 EcRE and three flanking bp on each side is an efficient EcR binding site. Mutational analysis confirms that the integrity of both these half-sites as well as their 1bp spacing are critical for binding of the ecdysone receptor. The D EcRE behaved as a much weaker EcR binding site than the hsp27 EcRE but a single bp substitution was sufficient to confer upon it a binding capacity equivalent to that of the hsp27 EcRE. These results have led us to propose the sequence PuG(G/T)T(C/G)A(N)TG(C/A)(C/A)(C/t)Py as a revised version of a previously proposed EcRE consensus sequence. PMID- 8485513 TI - Cloning of a Chironomus tentans cDNA encoding a protein (cEcRH) homologous to the Drosophila melanogaster ecdysteroid receptor (dEcR). AB - We have cloned a cDNA sequence coding for a Chironomus tentans steroid hormone receptor homologue which exhibits extensive amino acid sequence co-linearity with the ecdysteroid receptor of Drosophila melanogaster (dEcR; cell 67, 59-77). The DNA-binding domain has 95% and the hormone-binding domain 75% amino acid sequence identity with the cloned dEcR. The gene for this C. tentans protein is located on chromosome II, region 17C, as determined by in situ hybridization to polytene chromosomes of salivary glands. On Northern blots cDNA probes of the cloned gene hybridize to polyadenylated RNA of ca 4.2 kb. The expression of the cloned gene seems to be developmentally regulated and correlates to changes in ecdysteroid titer. Transfection of this C. tentans protein into D. melanogaster Schneider's line 2 cells leads to transcriptional interference with endogenous dEcR on an ecdysteroid-regulated promoter. PMID- 8485514 TI - Early steps in ecdysteroid biosynthesis: evidence for the involvement of cytochrome P-450 enzymes. AB - The first step in the biosynthesis of ecdysteroids by Manduca sexta prothoracic glands, the conversion of cholesterol to 7-dehydrocholesterol, is mediated by an enzyme with characteristics of a microsomal cytochrome P-450, i.e. sensitivity to CO and fenarimol, and a requirement for NADPH. The enzyme responsible for hydroxylation at C-25 of the putative 3-dehydroecdysone precursor, 14-hydroxy-5 beta-cholest-7-en-3,6-dione, is also microsomal, while those mediating hydroxylations at C-22 and C-2 of 3,14,25-trihydroxy-5 beta-cholest-7-en-6-one are mitochondrial. Indirect evidence revealed that the steps between 7 dehydrocholesterol and the trideoxyecdysteroids occur in the mitochondria, suggesting that extensive shuttling of intermediates between the endoplasmic reticulum and mitochondria takes place in the prothoracic gland cell during ecdysteroid biosynthesis. During the fifth larval instar, cholesterol 7,8 dehydrogenase activity is evident from days 2 to 9, while the conversion to [3H]ecdysteroids is not significant prior to the ecdysteroid commitment peak on day 4. Terminal hydroxylase activity shows little change throughout the instar. These data support the hypothesis that regulation of the biosynthetic pathway by PTTH occurs at the step immediately following the formation of 7 dehydrocholesterol. The steroid biosynthesis inhibitor, fenarimol, has been shown to inhibit each of these P-450 enzymes, as well as fat body ecdysone 20 monooxygenase, with an I50 of 10(-4) M in disrupted glands, suggesting that it is a general P-450 inhibitor. The secretion of ecdysteroids by the glands in vitro is very sensitive to fenarimol, i.e. I50 of 10(-6) M. RH5849, 1,2-dibenzoyl-1 tert-butylhydrazine, fails to inhibit any of these prothoracic gland reactions, yet strongly inhibits fat body ecdysone 20-monooxygenase activity. This suggests that RH5849 is a specific ecdysteroid substrate/product mimic in this reaction. PMID- 8485515 TI - Enhancer and silencer elements within the first intron mediate the transcriptional regulation of the beta 3 tubulin gene by 20-hydroxyecdysone in Drosophila Kc cells. AB - We have studied the transcriptional regulation of the beta 3 tubulin gene by the steroid hormone 20-hydroxyecdysone (20-E) in Drosophila Kc cells. A series of hybrid genes, with different fragments of the beta 3 tubulin gene driving the bacterial chloramphenicol acetyl transferase (CAT) gene were constructed. The promoter activity was assayed after transient expression in Kc cells, in the presence and the absence of 20-E. Constructs with 0.91 kb upstream from the transcription start site and 360 bp from the first large intron allowed the hormonal regulation, i.e. a repression in the absence of 20-E and a derepression activation in the presence of the hormone. This 360 bp fragment contains several enhancers and silencer(s) sequences. The regulation of the expression of the beta 3 tubulin gene results from the combined activity of all the positive and negative regulatory sequences of the first intron, and a dialogue with the promoter sequences. The nucleotide sequence of this intronic regulatory-fragment has been established and we have identified several EcRE (ecdysone responsive element) consensus sequences. PMID- 8485516 TI - The IVth Karlson Lecture: ecdysone-responsive genes. AB - Those of us who study ecdysone action share at least two important long-range goals: (i) to understand the developmental specificity of steroid action in full molecular detail, by integrating ecdysone action with our rapidly expanding knowledge of the molecular biology of insect development, and (ii) to better understand the nature of the steroid response and its evolution by taking advantage of the unparalleled opportunities for both genetic and comparative study afforded by the diversity of the "ecdysone world". However, until recently, the molecular fundamentals of the ecdysone system were unknown and our efforts have, of necessity, been devoted to their elucidation. Now that the situation has changed: we have a small but varied catalog of ecdysone-responsive genes for study and it is clear that some of these are tissue- and stage-specific in their expression. The ecdysone receptor (EcR), like other steroid receptors a member of the nuclear receptor family, is now accessible to molecular study, and we have a preliminary understanding of the DNA sequences (EcREs) that bind receptor and specify a gene as ecdysone-responsive. With these tools in hand and with the opportunity to turn to larger questions, it is a propitious moment to consider the nature of those questions and how ecdysone can contribute to the answers. PMID- 8485517 TI - The ultrastructure of the prothoracic gland/corpus allatum/corpus cardiacum ring complex of the Australian sheep blowfly larva Lucilia cuprina (Wied.) (Insecta: Diptera). AB - The ultrastructure of the constituent endocrine glands within the ring complex of Lucilia cuprina larvae has not been previously described. This study investigated the ring complex of mid-third instar larvae. Three distinct endocrine cell types were identified: (1) prothoracic gland (PTG) cells which constituted the major cell type; (2) corpus allatum (CA) cells, localized in the anterior central region, and (3) corpus cardiacum (CC) cells, located posteriorly, ventral to the aorta. PTG cells were identifiable by their large ovoid nuclei (9-14 microns dia, length 12-18 microns) and numerous cytoplasmic lipid vacuoles. The plasma membrane of peripheral PTG cells were invaginated to form intercellular channels. The CA cells are characterized by ovoid nuclei (6-7.5 microns dia, 6.5-9 microns length) and electron dense staining cytoplasm. Compared to PTG cells the CA cells had smaller nuclei and lower nucleus:cytoplasm cell ratio. Extensive networks of highly irregular, electron-lucent intracellular spaces, dispersed throughout the cytoplasm were also characteristic of CA cells at this developmental stage. These spaces often contained membrane bound lipid vacuoles occurring singly or as aggregates. The CC contained both intrinsic and extrinsic neural components. The intrinsic cells were characterized by circular nuclei (6.5-8.5 microns dia), prominent nucleolus and numerous cytoplasmic electron-dense neurosecretory granules (100-240 nm dia). The extrinsic axons and terminals within the CC contained electron-dense neurosecretory granules (80-150 nm), neurotubules and mitochondria. PMID- 8485518 TI - Effects of plant flavonoids and other allelochemicals on insect cytochrome P-450 dependent steroid hydroxylase activity. AB - The plant flavonoids flavone, chrysin, apigenin, kaempferol, morin, quercetin, myricetin and phloretin were found to inhibit in a dose-dependent manner the cytochrome P-450 dependent ecdysone 20-monooxygenase activity associated with adult female Aedes aegypti, wandering stage larvae of Drosophila melanogaster, and fat body and midgut from prewandering and wandering stage last instar larvae of Manduca sexta. The concentrations of these flavonoids required to elicit a 50% inhibition of the steroid hydroxylase activity in all the insects ranged from ca 1 x 10(-5) to 1 x 10(-3) M. In addition, lower concentrations (1 x 10(-6) to 1 x 10(-5) M) of the flavonols kaempferol, morin, quercetin and myricetin significantly stimulated (50-100% above control) M. sexta fat body ecdysone 20 monooxygenase activity. Other plant allelochemicals examined and found to significantly inhibit insect ecdysone 20-monooxygenase activity include corynanthine, quinidine, and quinine; whereas, indican and mimosine were found to significantly stimulate M. sexta fat body steroid hydroxylase activity. Several allelochemicals were without effect at all concentrations tested. Although none of the compounds tested in this study elicited effects at very low concentrations (1 x 10(-9) to 1 x 10(-8) M), the in vitro monooxygenase radioassay does hold considerable promise as a screening tool for the detection and identification of plant allelochemicals which may function as biopesticides affecting insect ecdysteroidogenesis. PMID- 8485519 TI - The arthropod initiator: the capsite consensus plays an important role in transcription. AB - Approximately 25% of arthropod RNA polymerase II-transcribed promoters contain one or more copies of the sequence TCAGT beginning within the interval (-10, +10). The clear statistical overrepresentation of this sequence and, to a lesser extent, of its cognates ACAGT, GCAGT, and TCATT, implies that they may be significant promoter elements. Their collective sequence similarity to vertebrate initiators (Inrs) of the TdT class suggests that the vertebrate and arthropod elements are homologous. Prior work in vertebrate systems has emphasized the role of the Inr in promoters lacking TATA boxes, where it can serve as an alternate staging site for polymerase II initiation. However, it is clear that the Inr sequence is by no means restricted to TATA-deficient promoters. Functional tests using the TATA-containing Drosophila gene Eip28/29 support the idea that the Inr is a facultative promoter element, required for efficient transcription under some conditions. For example, the Inr protects basal expression of Eip28/29 from the silencing effect of ecdysone response elements. In addition, the Inr is required for the function of an enhancer of basal activity in Eip28/29. We conclude that Inrs are promoter elements found sporadically throughout the higher eukaryotes, that the requirement for an Inr depends upon the array of other promoter elements which may be present in a given gene, and that Inrs may permit enhancers to discriminate among promoters. PMID- 8485520 TI - The E75 gene of Manduca sexta and comparison with its Drosophila homolog. AB - The ecdysone-inducible E75 gene responsible for the 75B puff of Drosophila melanogaster encodes a family of proteins which are members of the steroid receptor superfamily. These proteins are believed to be involved in the regulation of ecdysone response. In order to investigate the evolutionary conservation of E75, we have identified the E75 gene of Manduca sexta. We show here the structure of a cDNA believed to encode the Manduca homolog of the E75B protein, and demonstrate that the putative DNA binding, hormone binding and amino and carboxy terminal flanking domains are conserved. However, due to a relative reduction in intron size and number and the absence of homopolymeric amino acid repeats, the E75 B transcription unit and protein are considerably smaller in M. sexta than in D. melanogaster. These findings have implications for the identification of critical structural features of E75 and also suggest that E75 has a conserved function and a shared ligand in Lepidoptera. PMID- 8485521 TI - The reaction with polytene chromosomes of antibodies raised against Drosophila E75A protein. AB - The steroid insect molting hormone ecdysone rapidly induces a small number of polytene chromosome puffs in Drosophila. The Ashburner model proposes that the corresponding early genes encode proteins involved in both the induction of the late genes and the repression of the early genes. The Drosophila E75 early gene has been isolated and two of its products, E75A and E75B, have been shown to be members of the steroid receptor superfamily. We have now prepared antisera directed against A- and B-specific regions of the E75 proteins. Antisera and a monoclonal antibody raised against E75A, the major larval protein product of the E75 gene, bind to discrete sites in native salivary gland chromosomes. These sites are closely correlated with early and late ecdysone responsive loci. PMID- 8485522 TI - The galactose binding lectin from the beet armyworm, Spodoptera exigua: distribution and site of synthesis. AB - The Spodoptera exigua galactose binding lectin, extracted from hemolymph by affinity chromatography, was comprised of large molecular weight aggregates (100 700 kDa). SDS-PAGE of this lectin preparation revealed it to contain 2 subunits of 33.2 and 34.4 kDa in equimolar concentrations. These subunits had similar amino acid profiles, possessed identical N-terminal sequences and reacted equally to a bank of antilectin monoclonal antibodies. By staining Western blots with various lectin conjugate probes, we demonstrated that the 34.4 kDa subunit contains complex mannose residues, suggesting that this subunit is the glycosylated form of the 33.2 kDa subunit. The N-terminal sequence of the S. exigua lectin was distinct from other invertebrate galactose binding lectins. Light microscopy in combination with immunoelectron microscopy was used to localize the S. exigua lectin in the granules of the granulocyte class of hemocytes. Degranulation of these cells resulted in the release of the lectin. Isotope incorporation studies followed by immunoprecipitation with a S. exigua monoclonal antibody demonstrated that the fat body was the major site of lectin synthesis. Similar studies with hemocyte monolayers did not result in the production of detectable levels of 35S-labeled S. exigua lectin. PMID- 8485523 TI - Transcripts from a mosquito dihydrofolate reductase gene: evidence for heterogeneity at the 5' end. AB - Heterogeneity among transcripts from the mosquito (Aedes albopictus) dihydrofolate reductase (DHFR) gene in wild-type C7-12 cells and in methotrexate resistant Mtx-5011-128 cells has been analyzed by Northern blotting, RNAase mapping, and primer extension. In both sensitive and resistant cells, a major transcription initiation site mapped c. 11 nucleotides downstream of the TATAA box, near position -66 relative to the AUG codon. Two other major transcription initiation sites mapped approx. eight and 45 nucleotides, respectively, upstream of the TATAA box. In addition, at least six minor sites were detected, four of which mapped within TATA-like sequences. Within the AT-rich region flanking the 5'-end of the mosquito DHFR gene were four T-rich motifs and three "GTTTGTG" repeats. Additional "GTTTGTG" repeats occurred in the first exon and in the single 56 nucleotide intron of the mosquito DHFR gene. In contrast to the heterogeneity at the 5'-ends of mosquito DHFR transcripts, the 3'-end terminated at a single position, c. 22 nucleotides downstream of the polyadenylation signal. PMID- 8485524 TI - In vitro and in vivo proteolysis of the Bacillus thuringiensis subsp. israelensis CryIVD protein by Culex quinquefasciatus larval midgut proteases. AB - Proteases with trypsin-, chymotrypsin- and thermolysin-like specificity were detected in Culex quinquefasciatus larval midguts. Their activities were monitored by N-terminal amino acid sequence analysis of the Bacillus thuringiensis subsp. israelensis CryIVD toxin proteolytic fragments. These proteases are located in the larval midgut and in different fractions obtained during the preparation of brush border membrane vesicles. The activity of the midgut proteases increased with an increase in pH. Both the chymotrypsin- and thermolysin-like activities are involved in the processing of solubilized CryIVD toxin, whereas an additional trypsin-like protease is necessary for the CryIVD parasporal inclusion processing. The solubilized CryIVD toxin was first cleaved between Thr347 and Phe348 and between Phe348 and Tyr349, generating a 40-kDa N terminal fragment and a 32.5-kDa C-terminal fragment. The C-terminal domain was resistant to further processing, with only a small amount of a 31-kDa product appearing due to the action of a thermolysin-like protease. However, the N terminal domain was very unstable, and was further degraded to about 30 kDa. Unlike the solubilized CryIVD toxin, the processing of the CryIVD parasporal inclusion was very slow at neutral pH. Three protease-resistant products were detected at pHs higher than 9.5 with an overnight incubation at 37 degrees C. The 30- and 28.5-kDa C-terminal peptides are proteolytic products of trypsin- and chymotrypsin-like proteases, respectively; while the 28-kDa N-terminal peptide has 27 amino acids deleted from the N-terminal end by a thermolysin-like protease. PMID- 8485526 TI - Identification of two storage hexamers in the ant, Camponotus festinatus: accumulation in adult queenless workers. AB - Two electrophoretically and immunologically distinct storage hexamers (Hex 1 and Hex 2) have been identified in Camponotus festinatus workers. The molecular weights of the native molecules were estimated to be 460,000 (Hex 1) and 580,000 (Hex 2) by pore limiting gradient electrophoresis. Hex 1 partially dissociates with moderate alkaline pH. Both proteins are composed of a single type of apoprotein of approx. 73 (Hex 1) and 80 kDa (Hex 2). While most of Hex 2 is sequestered by the fat body before pupation, Hex 1 remains largely in the hemolymph during the last larval and pupal stages. Both proteins were detected only in low concentrations in the hemolymph of newly emerged adults, and they gradually disappear from adult workers maintained in the colonies. In queenless workers, however, Hex 1 and Hex 2 accumulate in the hemolymph and fat body, constituting the most abundant proteins together with vitellogenin. Camponotus festinatus storage hexamers bear some homologies in their N-terminal sequence with the arylphorins of Diptera and Lepidoptera, as well as with a crab hemocyanin. However, with respect to their amino acid composition, they can not be classified as arylphorins. PMID- 8485525 TI - Expression and characterization of cDNAs for cecropin B, an antibacterial protein of the silkworm, Bombyx mori. AB - To analyze the induction mechanism of antibacterial protein gene expression, cDNAs coding for cecropin B have been cloned from the B. mori fat body cDNA library. Nucleotide sequences of two positive clones were determined and their amino acid sequences deduced. They revealed that these clones coded for the same cecropin, which is identical to purified cecropin B. However, the cDNAs contained different nucleotides at the third codon position and 5' or 3' non-coding regions. Results obtained by Northern blot analysis showed that the gene expression of B. mori cecropin B was rapidly induced by Escherichia coli and reached maximum levels 8 h after immunization. The expression of cecropin B gene occurred specifically in tissues, mainly in the fat body and hemocytes. PMID- 8485527 TI - DNA polymerase-beta from the pupal ovaries of Bombyx mori. AB - The silk glands of Bombyx mori, a highly replicative tissue contains high levels of DNA polymerases alpha, delta and epsilon but not DNA polymerase-beta. However, we detected the latter activity in the gonadal tissues, viz. the pupal ovaries and testes of B. mori. The enzyme has been purified to homogeneity from the pupal ovaries by a series of column chromatographic and affinity purification steps. The enzyme satisfied the criteria to be designated as DNA polymerase-beta based on its small size, requirement for high concentration of monovalent cations for catalytic activity, sensitivity to ddTTP and insensitivity to aphidicolin. It is a monomeric polypeptide of M(r) 40 kDa, and the Km for dNTPs ranges between 8-20 microM. DNA polymerase-beta is biochemically and immunologically distinct from DNA polymerase-alpha from the silk glands of B. mori. The enzyme showed a preference for gapped DNA, and could not elongate ultraviolet irradiated template beyond the pyrimidine dimers. The absence of any associated primase and exonuclease activities from this enzyme, and its conspicuous absence in the highly replicative tissue, imply that it is unlikely to participate in the DNA endoreplication process. PMID- 8485528 TI - Levels of biogenic amines and peptides in individual corn earworm moths, Helicoverpa zea, using high performance liquid chromatography with electrochemical detection. AB - Quantitative levels of octopamine, serotonin, and dopamine were measured from brain and corpus cardiacum in individual male and female Helicoverpa zea, using high performance liquid chromatography (HPLC) with electrochemical detection. By increasing the proportion of organic modifiers in the mobile phase we were also able to quantify two peptides, adipokinetic hormone and hypertrehalosemic hormone. Levels of amines in both tissues were similar in males and females, but with greater quantities in the brain than the corpus cardiacum. In contrast, the two hormones were found predominantly in the corpus cardiacum, with the level of adipokinetic hormone three times greater than that of the hypertrehalosemic hormone, a finding in agreement with other studies. The described methodology demonstrates the power of HPLC with electrochemical detection for analysis of amines and peptides found in small quantities within the nervous tissue of individual insects. PMID- 8485529 TI - Primary structure of a 14 kDa basic structural protein (Lm-76) from the cuticle of the migratory locust, Locusta migratoria. AB - The complete amino acid sequence of a 14 kDa structural protein (LM-76) isolated from pharate cuticle of the locust, Locusta migratoria, was determined by Edman degradation of the intact protein and enzymatically derived peptides. Plasma desorption and electrospray mass spectrometry was used as an integrated part of the structure determination. Protein Lm-76 has characteristics similar to proteins previously isolated from the pharate locust. The amino acid composition shows a high content of alanine (32%) and absence of the amino acids Glu, Cys, Met, Phe and Trp. The sequence has a central hydrophilic region surrounded by two hydrophobic regions with 7 repeats of a (Tyr)-Ala-Ala-Pro-Ala/Val motif. The conservation around the prolyl residues within this sequence motif is demonstrated for the hitherto sequenced presumptive exocuticle proteins from L. migratoria. The N-terminal region of protein Lm-76 is enriched in the amino acids Gly, Leu and Tyr located in the conserved sequence NH2-Gly-Tyr-Leu-Gly-Gly-(Tyr) . PMID- 8485530 TI - Multivariate nonparametric analysis for the two-period crossover design with application in clinical trials. AB - Nonparametric methods are presented for the analysis of the two-treatment, two period crossover design with multivariate response. After forming within-subject sums and differences, the usual tests, including those for carry-over effects and direct treatment effects, can be constructed using a multivariate analysis of variance. When the assumptions relevant to traditional analysis are in question, multivariate nonparametric tests based on ranks provide a realistic alternative. However, multivariate response gives rise to a wider class of hypotheses than is seen in crossover designs with univariate response. We discuss these hypotheses and formulate nonparametric tests for associated analyses. PMID- 8485531 TI - Statistical methods for a three-period crossover design in which high dose cannot be used first. AB - Design and analysis methods for the three-period crossover trial defined by the sequences: (D0, D1, D2), (D1, D0, D2), and (D1, D2, D0), where D0 is a placebo, and D1 and D2 are a low dose and a high dose of a drug, respectively, are developed. This design may be used when investigators are unwilling to administer a higher dose of a new drug to a patient before administering a lower dose. In using this design, patients should be randomized to sequences in blocks that are integer multiples of 3. Both parametric and non-parametric analysis methods are based on contrasts that capture intrapatient variability only and provide unbiased estimates and hypothesis tests of pairwise differences between carryover, direct dose, and period effects. The design and methods are illustrated with data reflecting the cognitive component of the Alzheimer's disease assessment scale collected in a large clinical trial of Tacrine at doses of 0, 40, and 80 mg/day. PMID- 8485532 TI - Analysis of the 2 x 2 crossover design with subsampling. AB - Subsampling can be used in experimental design to investigate extraneous sources of variability. One useful strategy is to make independent replicate measurements of the response variate. This can be achieved in clinical studies, for example, by dividing a blood or urine specimen from each of a sample of subjects into aliquots and processing these through a chemistry laboratory in such a way that the replicate determinations are independent. This procedure can be used to increase design efficiency. This paper addresses considerations in the design and analysis of the 2 x 2 crossover plan with this type of subsampling. PMID- 8485533 TI - Exposure analysis of dichotomous response measures in long-term studies. AB - Differential exposure to study medications in long-term studies of some cardiovascular compounds complicates analyses, particularly the usual intention to-treat analyses and inferences therefrom of the data collected. Analysis methods that incorporate exposure are developed, presented, and illustrated by applying them to primary response data from a long-term, placebo-controlled, ancillary trial of gemfibrozil. The analysis methods address the extent to which end-points are correlated with the actual use of the compound rather than the extent to which end-points are correlated with the random assignment to double blind study medications. PMID- 8485534 TI - A simple stopping rule for declaring treatment ineffectiveness in clinical trials. AB - We consider the problem of stopping a clinical trial before its scheduled termination due to the apparent ineffectiveness of the experimental therapy, as compared with a control. We propose a simple-to-implement, intuitive decision rule based on the unadjusted attained significance levels from any appropriate statistical test. The proposed procedure may be used at any time during the study as an aid to help determine whether the study of an experimental treatment should be terminated early with the conclusion of treatment ineffectiveness. Much of the power of the usual fixed-sample test is retained while maintaining the nominal test size. PMID- 8485535 TI - Some general estimation methods for nonlinear mixed-effects models. AB - A nonlinear mixed-effects model suitable for characterizing repeated measurement data is described. The model allows dependence of random coefficients on covariate information and accommodates general specifications of a common intraindividual covariance structure, such as models for variance within individuals that depend on individual mean response and autocorrelation. Two classes of procedures for estimation in this model are described, which incorporate estimation of unknown parameters in the assumed intraindividual covariance structure. The procedures are straightforward to implement using standard statistical software. The techniques are illustrated by examples in growth analysis and assay development. PMID- 8485536 TI - Analysis of multivariate parallel-line bioassay with composite responses and composite doses, using canonical correlations. AB - The use of a composite response to estimate the relative potency in a multivariate parallel-line bioassay is described by Finney. Occasionally a multivariate bioassay has multiple drugs also. Such a situation arises, for example, when a treatment contains several drugs. A procedure for combining multiple responses and combining multiple drugs is proposed in this paper, in order to obtain point and interval estimates of the relative potency. A composite response and a composite dose level for this purpose are obtained by using canonical analysis. PMID- 8485537 TI - The likelihood ratio for comparing means when a portion of the subjects fail to respond. AB - Results of clinical studies are often obscured by the fact that some of the subjects improve with treatment while others do not. As a consequence, for example, we may obtain a contaminated distribution in a treatment group, having one component similar to the entire distribution for a control group and the other shifted by the treatment effect. Maximum-likelihood estimation and the likelihood ratio test for investigating the proportion of responders together with the treatment effect are based on asymptotic theory and use iterative maximization techniques. We investigate the sampling distribution of the estimates and the test and demonstrate their use in statistical inference. Our results suggest that the chi-square distribution with 1.4 degrees of freedom provides a useful test criterion even when the sample sizes are as small as 10. Only in obvious testing situations is the t-test adequate. PMID- 8485538 TI - Evaluation of parametric and nonparametric two one-sided tests procedures for assessing bioequivalence of average bioavailability. AB - A simulation study was conducted to compare the levels of significance and power between Schuirmann's and nonparametric two one-sided tests procedures for a 2 x 2 crossover design under different combinations of sample sizes, intrasubject variabilities, and underlying distributions. Empirical results suggest that Schuirmann's two one-sided tests procedure is robust to minor departure from the assumption of normality. PMID- 8485539 TI - Radial glia-like cells in the supraoptic nucleus of the adult rat. AB - Conventional light and confocal microscopy of thick vibratome sections of the hypothalamus of adult male and female rats immunostained for the astrocytic marker glial fibrillary acidic protein (GFAP) revealed that the supraoptic nucleus (SON) contains two morphologically distinct types of astrocytes. One has a stellate form, similar to that of most astrocytes in the adult CNS. The other has a morphology reminiscent of radial glia in the developing CNS: from their cell bodies, located along the ventral glia lamina (VGL), arise one long thick process that spans the SON in the coronal plane, several horizontally-oriented processes that form a dense network in the VGL, and a short process oriented towards the pia. The latter astrocytes are immunoreactive for vimentin, an intermediate filament protein of immature glial cells and a marker for radial glia. The stellate astrocytes showed no vimentin immunoreactivity. The functional significance of each type of supraoptic astrocyte is at present unknown but the presence of radial glia-like cells in this hypothalamic region suggests that the SON retains a certain degree of immaturity during adulthood, that may be linked to its well known capacity to undergo neuronal-glial plasticity under physiological and experimental stimulation. PMID- 8485540 TI - Altered ratios of beta-endorphin: beta-lipotropin released from anterior lobe corticotropes with increased secretory drive. I. Effects of diminished glucocorticoid secretion. AB - Previous studies have demonstrated that acute stress or ovine corticotropin releasing hormone (oCRH) in vivo, or oCRH in vitro, stimulates release of beta endorphin over beta-lipotropin from anterior pituitary corticotropes. This occurs despite the predominance of beta-lipotropin in corticotrope peptide stores. In vitro studies with primary anterior pituitary cultures suggested that chronic exposure to oCRH results in a shift towards more beta-lipotropin secretion into the media than with short-term exposure. The current studies explored whether increased secretory drive in vivo results in a similar shift towards more beta lipotropin. We used removal of glucocorticoids by adrenalectomy or metyrapone blockade of corticosterone synthesis, to stimulate endogenous secretion of CRH and vasopressin. Both treatments resulted in shifts of the ratio of beta endorphin: beta-lipotropin in plasma of experimental animals in comparison to the sham-treated control rats. In vitro testing with oCRH of anterior lobe cultures from adrenalectomized or metyrapone-treated rats demonstrated similar effects of these treatments on the ratio of beta-endorphin:beta-lipotropin. These changes occurred despite similar ratios of beta-endorphin:beta-lipotropin in anterior pituitary peptide stores. PMID- 8485541 TI - Arginine vasopressin-induced sensitization in brain: facilitated inositol phosphate production without changes in receptor number. AB - Arginine vasopressin (AVP) has been shown to have a unique sensitization effect whereby repeated injection of AVP into a lateral cerebral ventricle or a mediobasal region of the rat forebrain below the lateral septum and including the anterior hypothalamus referred to as the ventral septal area, causes enhanced motor responses to the ligand. To elucidate possible neuronal mechanisms responsible for AVP sensitization, 1) we determined the dose and the time required for the development and expression of AVP sensitization, and 2) we tested the hypotheses that AVP sensitization may result in a) alteration of septal AVP V1 receptor affinity or number, and/or b) alteration of septal AVP V1 receptor signal transduction (phosphatidylinositol hydrolysis) mechanisms. Our behavioral data show that the magnitude of AVP sensitization varies with dose and time, and the effect is dependent on the time interval between injections, in that an initial intracerebroventricular AVP injection enhances the sensitivity of the animals to the motor effects of similar AVP injections given 6 h to 6 days later but not to injections given hourly or weekly. No changes in septal AVP binding site density and affinity, as measured by [3H]AVP binding to septal synaptic plasma membrane, were found in sensitized animals; [3H]inositol monophosphate stimulation in response to AVP in septal slices, however, was found to be significantly enhanced. This enhanced [3H]inositol monophosphate stimulation appears specific to a V1-type receptor because it was significantly reduced in the presence of the V1 receptor antagonist, d(CH2)5Tyr(Me)AVP, and was not found using oxytocin or the V2 receptor agonist, DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485542 TI - Ovariectomy increases in vivo luteinizing hormone-releasing hormone release in pubertal, but not prepubertal, female rhesus monkeys. AB - In pubertal, but not prepubertal, monkeys ovariectomy (OVX) results in an elevation of circulating luteinizing hormone (LH) levels. To determine if the castration-induced LH increase in pubertal monkeys is due to an increase in pulsatile LH-releasing hormone (LHRH) release, effects of OVX on in vivo LHRH release in the stalk-median eminence were examined in fully conscious monkeys using a push-pull perfusion method. The average ages (+/- SEM) of female rhesus monkeys in each group at OVX were 14.5 +/- 0.6 months (n = 6; prepubertal), 25.0 +/- 1.3 months (n = 5; early pubertal) and 37.8 +/- 2.1 months (n = 6; midpubertal). Perfusate samples from the stalk-median eminence were obtained in 10-min fractions for 6 h in the morning (0600 to 1200 h) and 6 h in the evening (1800 to 2400 h), from the same subjects before OVX, and at 29 days and approximately 100 days after OVX. LHRH levels in perfusates were measured by radioimmunoassay. LH levels throughout the experiment were monitored by periodic blood sampling. OVX resulted in a significant LH increase in early and midpubertal monkeys (P < 0.001 for both), but not in prepubertal monkeys. Similarly, OVX in early and midpubertal monkeys increased mean LHRH release when examined 29 days after surgery (P < 0.05 and P < 0.01, respectively). The OVX induced LHRH increases in early and midpubertal monkeys remained elevated at approximately 100 days postcastration. Furthermore, it was found that effects of OVX on the increased LHRH release were primarily due to the elevation of basal release and pulse amplitude, but not pulse frequency. In contrast, OVX did not cause any significant effects on pulsatile LHRH release in prepubertal monkeys. The results indicate that an increase in LHRH release and a concomitant increase in circulating LH occurs after OVX in pubertal monkeys, but not in prepubertal monkeys. These data are consistent with the hypothesis that the low level of LH in circulation before the onset of puberty is due to a low amount of LHRH release which is independent of ovarian steroid feedback and that the maturity of the neuronal control system for the pulsatile LHRH release is responsible for the onset of puberty. After the onset of puberty, the negative feedback of ovarian steroid hormones becomes important to the regulation of gonadotropin release. PMID- 8485543 TI - Effects of lipocortin 1 and dexamethasone on the secretion of corticotrophin releasing factors in the rat: in vitro and in vivo studies. AB - Lipocortin 1 (LC1: also called annexin 1) was first described as a putative second messenger protein for the anti-inflammatory steroids in peripheral tissues. In the present study, in vitro and in vivo methods were used to examine its potential role within the hypothalamus as a mediator of the regulatory actions of the glucocorticoids on the hypothalamo-pituitary-adrenocortical axis of the rat. In the in vitro studies, the effects of human recombinant LC1 (hu-r LC1) on the concomitant release of the two major corticotrophin-releasing factors (CRF-41 and arginine vasopressin, AVP) from isolated hypothalami removed from chronically adrenalectomized rats were compared with those of dexamethasone in the presence and absence of appropriate secretagogues, namely phospholipase A2 (PLA2), interleukin-6 (IL-6) and a non-specific depolarizing agent, K+ (56 mM). The spontaneous release of CRF-41 in vitro was unaffected by either hu-r-LC1 (5 to 100 ng/ml) or dexamethasone (1 microM). Both compounds however reduced the release of the neuropeptide evoked by IL-6 (5 ng/ml) but failed to modify the secretory responses to PLA2 (25 U/ml) or K+ (56 mM). Dexamethasone (1 microM) had no effect on the basal release of AVP but effectively blocked the secretion of the peptide induced by either IL-6 (10 ng/ml) or PLA2 (25 U/ml). In complete contrast, hu-r-LC1 (5 to 100 ng/ml) stimulated the release of AVP and potentiated the secretory responses to IL-6 (10 ng/ml) and PLA2 (25 U/ml) but not to K+ (56 mM). The hypothalamic responses to PLA2 stimulation (25 U/ml) were associated with significant (P < 0.01) increases in prostaglandin E2 release which, in some instances, were potentiated by hu-r-LC1 (5 to 20 ng/ml). In vivo, administration of histamine (0.6 mg/100 g body wt, ip) produced significant (P < 0.01) increases in the serum corticosterone concentration and in the hypothalamic LC1 content. Neither hu-r-LC1 (0.6 to 1.2 micrograms) nor a polyclonal anti-LC1 antibody (3 microliters, diluted 1:200), injected intracerebroventricularly (icv), influenced either the resting serum corticosterone concentration or the hypersecretion of the steroid evoked by histamine stress. A lower dose of the recombinant protein (0.3 micrograms icv) also failed to alter basal corticosterone release but, in contrast to the higher doses, potentiated the pituitary-adrenocortical responses to histamine. The results suggest that LC1 may contribute to some aspects of peptide release in the hypothalamus but that its actions are not necessarily related to those of the glucocorticoids. PMID- 8485544 TI - Colchicine-induced accumulation of estrogen receptor and progestin receptor immunoreactivity in atypical areas in guinea-pig brain. AB - Using immunocytochemical techniques, cells containing estrogen and progestin receptors have been observed in many discrete regions of the guinea-pig forebrain, including the mediobasal hypothalamus and preoptic area. While most reaction product is located within cell nuclei, we have reported abundant reaction product in perikaryal cytoplasm and neuronal processes as well. Ultrastructural analysis has revealed the presence of estrogen and progestin receptors in atypical subcellular sites within the hypothalamus, including dendrites and axon terminals. In order to determine if microtubule-dependent intracellular transport is involved in intraneuronal transport of steroid hormone receptors, ovariectomized guinea-pigs were injected intracerebroventricularly with the microtubule inhibitor, colchicine, and brain sections at the level of the hypothalamus were immunostained for estrogen receptors. This treatment resulted in the appearance of estrogen receptor immunoreactivity in the paraventricular and mediodorsal thalamic region, areas typically devoid of estrogen receptor-immunoreactive cells in guinea-pigs. In a second study on progestin receptors, we observed the colchicine-induced accumulation of progestin receptor immunoreactivity in the paraventricular thalamic, mediodorsal thalamic and lateral dorsal thalamic areas as well as in the medial amygdala, all areas typically devoid of progestin receptor immunoreactivity. While estradiol injection induced progestin receptor immunoreactivity in the hypothalamus and preoptic area as described previously, it had no effect on the colchicine-induced accumulation in the thalamus and amygdala. These results provide evidence that in some neurons, progestin receptors and estrogen receptors are transported intracellularly, apparently at a rapid enough rate that they do not ordinarily accumulate within the perikaryon. PMID- 8485545 TI - The maintenance of normal parturition in the rat requires neurohypophysial oxytocin. AB - The neuropeptide oxytocin has long been known as a potent contractor of the uterus. However, it has remained difficult to attribute a definite role for neurohypophysial oxytocin in either the initiation or continuation of labour. Most recently, Lefebvre and colleagues have suggested that oxytocin produced in the uterus, rather than in the hypothalamus, may be more important in parturition since at term the uterus of the rat contains 70-fold more mRNA for oxytocin than the hypothalamus, and this disappears at about the time of parturition. Despite the high levels of mRNA the uterus contains only nanogram quantities of immunoreactive oxytocin per gram wet weight at term, compared to microgram quantities present in the pituitary. Here we show that activation of the neurohypophysial oxytocin system occurs, as reflected by expression of immunoreactivity for Fos in the hypothalamic supraoptic nucleus, and that this activation is indeed critical for normal parturition, since its inhibition results in a significant prolongation of parturition. In addition, we present evidence that pulsatile delivery of oxytocin into the circulation is important for the efficient progress of parturition, indicating that a major role of the neuronal circuits regulating oxytocin secretion for parturition, as is already known for suckling, is to produce an appropriately patterned hormonal output for efficient biological action. PMID- 8485546 TI - Hormonal control of sex differences in the brain, behavior and accessory sex structures of whiptail lizards (Cnemidophorus species). AB - The effects of steroid hormones on sexual dimorphisms in the brain, behavior and accessory sex structures were investigated in two species of whiptail lizards. The studies were conducted both in adults and hatchlings of a sexually reproducing species (Cnemidophorus inornatus) and an all-female species (C. uniparens) which displays 'sexual' behaviors typical of males and females. Adults were gonadectomized and approximately 3 months later given either a Silastic capsule filled with sex steroid or an empty capsule. Young animals of both species were left intact and given a capsule on the day of hatching. An additional group of C. uniparens was ovariectomized on the day of hatching. Following treatment, measures of oviduct (estrogen-dependent), renal sex segment (androgen-dependent) and wolffian duct (androgen-dependent) hypertrophy were taken in some experiments. Animals were also tested for sexual behavior in some of the studies. The volumes of the anterior hypothalamus-preoptic area and ventromedial hypothalamus were measured in each individual. Estrogen, testosterone and dihydrotestosterone stimulated peripheral structures at both time periods in both sexes and species. The hormones also stimulated courtship and copulatory behaviors in many of the adult animals. However, testosterone in the anterior hypothalamus-preoptic area of male C. inornatus was the only treatment which produced parallel effects on the volume of a brain area and the behaviors which it controls. These data add whiptail lizards to the list of species in which steroid hormones affect the volume of brain regions in adulthood, but suggest that such changes in morphology are not necessarily predictive of functional differences. PMID- 8485547 TI - Potential corticotropin-releasing factor pathways in the rat brain as determined by bilateral electrolytic lesions of the central amygdaloid nucleus and the paraventricular nucleus of the hypothalamus. AB - The projection fields of corticotropin-releasing factor (CRF)-containing perikarya in the rat central nervous system were studied using a combination of electrolytic lesions, microdissection and radioimmunoassay. The effects of bilateral electrolytic lesions of the central nucleus of the amygdala (Ce) or the paraventricular nucleus (PVN) of the hypothalamus were measured by a sensitive and specific radioimmunoassay. Following lesions of the Ce, CRF concentrations in the locus ceruleus (LC) were significantly decreased. Following lesions of the PVN, CRF concentrations in the median eminence were markedly decreased (> 85%), with smaller but consistent reductions of CRF in the hippocampus as well. In contrast to the Ce lesions, PVN lesions resulted in increases in CRF concentrations in the LC. These results further confirm the projection of CRF containing cells from the PVN to the median eminence, provide evidence for a PVN hippocampal CRF pathway, and suggest that the PVN modulates CRF neurons innervating the LC. Moreover, the existence of a CRF-containing pathway from the Ce to the LC appears likely, and such a circuit may play a role in the behavioral and physiological responses to stress. PMID- 8485548 TI - Lesions of the suprachiasmatic nucleus indicate the presence of a direct vasoactive intestinal polypeptide-containing projection to gonadotrophin releasing hormone neurons in the female rat. AB - In non-seasonal breeders like the rat, the influence of the suprachiasmatic nucleus (SCN) on reproduction is most clearly expressed in the female. Complete lesions of the SCN induce persistent oestrus (anovulation) in intact female rats, whereas oestrogen implantation in ovariectomized rats results in daily luteinizing hormone surges. Vasoactive intestinal polypeptide (VIP), a peptide synthesized in cell bodies of the SCN, inhibits the increase in pulsatile luteinizing hormone release observed in ovariectomized female rats. In search of the anatomical basis for these observations, the present study employs an immunocytochemical double staining for VIP and gonadotrophin-releasing hormone (GnRH) at the light microscopical level. It was demonstrated that approximately 45% of the GnRH positive neurons in the diagonal band of Broca, the preoptic and anterior hypothalamic area of female rats are innervated by VIP-containing processes. To investigate whether these VIP-containing fibres represent a direct projection of the SCN to the GnRH system, unilateral thermic SCN lesions were made. Lesions that unilaterally destroyed the majority of the VIP synthesizing cells in the SCN resulted in at least a 50% decrease of the VIP innervation of GnRH cell bodies at the lesioned side compared to the intact side. Lesions not affecting the VIP synthesizing cell population in the SCN did not change the percentage of GnRH neurons innervated by VIP-containing fibres, while partial lesions resulted in intermediate effects. These results indicate that the majority of the light microscopical VIP-containing input on GnRH neurons in the hypothalamus is derived from the SCN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485549 TI - Acetyl-L-carnitine effect on pituitary and plasma beta-endorphin responsiveness to different chronic intermittent stressors. AB - The aims of the present study were: 1) to compare the effect of two different chronic intermittent stressors i.e. cold-swimming versus ether, on the pituitary opioidergic system; 2) to evaluate the response of pituitary and plasma beta endorphin (beta-EP) to an acute stress in chronically stressed rats; and 3) to evaluate the effect of acetyl-l-carnitine treatment (10 mg/day/rat per os at night) on pituitary and plasma beta-EP changes induced by two different types of chronic stress. The stressors were applied twice a day for 10 days. Rats were killed either before, during or after the last swimming or ether stress session. beta-EP was measured by radioimmunoassay in anterior pituitary and in neurointermediate lobe extracts and in plasma. The following observations were made: 1) Chronic intermittent cold-swimming stress increased anterior pituitary contents and plasma beta-EP levels; 2) both chronic intermittent cold-swimming stress and ether stress caused an increase of neurointermediate lobe beta-EP contents; 3) as in control animals, rats exposed to chronic intermittent swimming stress reduced pituitary beta-EP contents and raised plasma beta-EP levels in response to the last acute swimming stress; 4) in contrast to control animals, rats exposed to chronic intermittent ether stress did not show any significant response of the pituitary-plasma opioidergic system to the last acute ether session; 5) the acetyl-l-carnitine treatment counteracted the changes evoked by chronic intermittent cold-swimming stress on the pituitary and plasma beta-EP levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485550 TI - Development of gonadotrophs and thyrotrophs in the female foetal sheep pituitary: immunocytochemical localization studies. AB - In order to investigate the ontogenesis of cell types in the pituitary gland, anterior pituitaries were collected from female foetal sheep at days 70, 100 and 130 of gestation (term = 145 days). Cells containing the common alpha-subunit and the specific beta-subunits of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were immunolocalized using the avidin-biotin immunoperoxidase technique. LH beta-containing cells were first detected in the foetal pituitary by day 70 of gestation. The number and intensity of staining of these LH beta cells increased by day 100 but had declined again by day 130. Immunopositive alpha-subunit and FSH beta-cells appeared by day 100 of gestation and had further increased in number and staining intensity by day 130. Cells containing TSH beta were present at day 70 and progressively increased in abundance and intensity through gestation. These data indicate that the development of LH- and FSH-containing cells in the female foetal sheep pituitary is differentially regulated during foetal life, and that in the sheep free alpha subunit is not produced in significant amounts before the specific beta-subunits. PMID- 8485551 TI - Endocrine actions of central neuropeptide Y in the ewe: activation of the hypothalamo-pituitary-adrenal axis by exogenous neuropeptide Y and role of endogenous neuropeptide Y in the secretion of luteinizing hormone during the oestrous cycle. AB - Neurons immunoreactive for neuropeptide Y (NPY) are abundant in the hypophysiotrophic areas of the brain. In particular, there is considerable anatomical evidence for the influence of this neuropeptide on the reproductive and hypothalamo-pituitary-adrenal axes. We therefore investigated whether central administration of NPY can alter the activities of the reproductive and hypothalamopituitary-adrenal axes in the ewe, and whether ovarian steroids are involved in the modulation of these events. We also attempted to investigate whether endogenous NPY is important in the control of luteinizing hormone releasing hormone/luteinizing hormone (LHRH/LH) secretion in the sheep oestrous cycle. Central injection of NPY (0.15 and 1.5 nmol in 50 microliters saline), delivered by gravity flow into the third cerebral ventricle, had no effect on LH levels in ovariectomized (OVX) ewes (n = 6) or OVX ewes implanted with oestradiol (OVX/E2) (n = 7), nor was LH secretion altered by central NPY (1.5 nmol) in intact cycling animals in either the follicular or the luteal phase (n = 5). However, central administration of 1.5 nmol NPY to intact ewes during both the follicular (P < 0.05) and the luteal phase (P < 0.01), and in OVX/E2 ewes (P < 0.05) caused a large and significant increase in plasma cortisol levels. High titre antibodies were raised to NPY in sheep and the effects of peripheral and central (intracerebroventricular) administration of anti-NPY antibodies on the timing and/or characteristics of the E2-induced LH surge in anoestrous ewes and of the preovulatory surge of LH in cycling ewes were determined. Intravenous administration of anti-NPY antibodies (n = 6) had no effect on the oestradiol benzoate-induced LH surge, compared with the control injection of non-immune plasma (n = 6). Likewise, passive systemic immunization against NPY (n = 10) was without effect on the characteristics of the preovulatory LH surge, compared with the control group (n = 10). However, central (intracerebroventricular) administration of anti-NPY antibodies (n = 4) delayed or abolished the preovulatory LH surge when compared with non-immune plasma treatment in the same animals. In summary, tonic LHRH/LH secretion is unaffected by centrally administered NPY at the doses used in this study. However, the same doses of NPY activate the hypothalamo-pituitary-adrenal axis, thus lending clear support to the hypothesis that NPY is involved in the multifactorial regulation of adrenocorticotrophin and cortisol secretion in this species, probably by stimulating corticotrophin-releasing hormone and/or arginine vasopressin secretion within the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8485552 TI - Corticotropin-releasing hormone neurons in the paraventricular nucleus project to the external zone of the median eminence: a study combining retrograde labeling with immunocytochemistry. AB - Corticotropin-releasing hormone (CRH) is the major regulator of the pituitary adrenal axis. CRH-immunoreactive perikarya are widely distributed in the central nervous system; however, only those which participate directly in the regulation of adrenocorticotropin are connected to the portal circulation in the external zone of the median eminence. The present study describes the identification of these hypophysiotropic neurons using retrograde labeling and CRH immunocytochemistry. Fluoro-Gold was injected peripherally then, 5 days later, the animals were treated with colchicine. Twenty-four hours later the animals were sacrificed, and their brains were immunostained for CRH with the indirect immunofluorescence technique. The results indicate that the vast majority of the Fluoro-Gold-accumulating and CRH-immunopositive perikarya (hypophysiotropic neurons) are located in the medial parvicellular subdivision of the paraventricular nucleus (PVN). However, not each CRH-immunoreactive neuron contains Fluoro-Gold, i.e. a small portion of these neurons project to areas of the brain other than the median eminence. The anterior, lateral and periventricular subdivisions of the PVN also contain hypophysiotropic CRH immunoreactive perikarya, however, their number is much less than in the medial parvicellular subdivision. Scattered double-labeled cells are also present in the medial preoptic area and the dorsal hypothalamus, just behind the PVN. These results support previous observations that the PVN, particularly the medial parvicellular subdivision, is the predominant source of the hypophysiotropic CRH neurons. PMID- 8485553 TI - In vitro regulation of rat prolactin messenger ribonucleic acid poly(A) tail length: modulation by bromocriptine. AB - Recent analysis of endocrine gene transcripts has revealed that several hormone mRNAs exhibit regulated size changes (due to alterations in length of the 3' poly(A) tail) which may function as an additional level of control in the determination of gene expression. We have now shown, through the novel application of an organ culture technique, that prolactin mRNA exhibits a similar regulated change in poly(A) tail length when rat anterior pituitary glands are explanted. The effect is observed in glands of either male or female rats and is specific with respect to growth hormone and alpha-tubulin mRNAs. Furthermore, we have also found that the size change in prolactin mRNA is attenuated in the presence of bromocriptine, indicating regulation through a dopaminergic pathway. PMID- 8485554 TI - Does lupus flare during pregnancy? PMID- 8485555 TI - The clinical significance of autoantibody profiles in patients with systemic lupus erythematosus. AB - We have evaluated the autoantibody profiles in the sera of 117 patients with systemic lupus erythematosus (SLE) and compared and contrasted the clinical and laboratory features of the disease of patients segregated according to an autoantibody profile. Using this approach we are able to demonstrate that autoantibody profiles identified subsets of patients with SLE. Patients with a negative autoantibody profile had fewer clinical and laboratory features of their disease when compared to the other subsets of patients. In contrast, patients with profile A (anti-nDNA and/or anti-Sm antibodies) had a statistically significant increase in malar rash, renal and hematologic involvement and hypocomplementemia when compared to patients with a negative profile. Patients with profile B (anti-nRNP antibodies) had a clinical pattern of disease different from that of patients with profile A and had a statistically significant increase in Raynaud's phenomenon when compared to patients with a negative profile. Patients with profile C (anti-SSA and/or anti-SSB antibodies) had a statistically significant increase in lupus-related rashes and photosensitivity. None of the lupus patients reviewed in this study has profile D (antibodies to centromere and/or Scl-70), this profile being seen largely in patients with scleroderma or one of its variants. Both patients with profile E (anti-histone antibodies) had drug-induced lupus. We conclude that the use of autoantibody profiles defines subsets of patients with lupus that may have clinical, therapeutic and prognostic implications. PMID- 8485556 TI - Expression and relationships of seven public idiotypes of DNA-binding autoantibodies on monoclonal antibodies and serum immunoglobulins. AB - Many studies have shown that DNA-reactive autoantibodies share cross-reactive public idiotypes that are defined, usually, by single anti-idiotype reagents. Because anti-idiotype antibodies or antisera will be limited in their ability to detect all the idiotopes of a particular antibody, their use will tend to underestimate the full extent of idiotype sharing between different antibodies. In order to define more comprehensively the extent of idiotype sharing in DNA autoantibodies, a panel of DNA-binding monoclonal autoantibodies from lupus mice was examined with a range of anti-idiotype antisera prepared in rabbits (five sera), guinea pigs (four sera) and a sheep. Each idiotype was detected on more antibodies than its original reference monoclonal antibody, and idiotopes of each were also present on serum immunoglobulins from lupus mice. Of 23 monoclonal antibodies 65% reacted with one or more of the anti-idiotype reagents. On these criteria, all the idiotypes were public; none was private in its expression. In about half the cases the idiotypes were located in or near the antigen-binding sites of the antibodies, but a direct relationship to specificity was not obvious except in the case of Id.228 present on antibodies with a relatively high affinity for single-stranded DNA. In other cases there was no obvious relationship between idiotype and specificity. Antibodies from the same mouse did not each express the same array of idiotopes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485557 TI - Systemic lupus erythematosus in Argentina: an overview. PMID- 8485558 TI - Brain synaptosomal antibodies in systemic lupus erythematosus. AB - Nervous system involvement in systemic lupus erythematosus (SLE) has been linked to the production of autoantibodies that may bind to surface antigens on neuronal cells and cause cellular dysfunction. At present, little is known of the target antigens recognized by these antibodies. The aim of the present study was to examine reactivity to rat brain synaptosomes (RBS) in sera from patients with SLE. Sera from 73 unselected SLE patients and controls were studied. Crude RBS were prepared by differential centrifugation and enriched fractions of synaptosomes (SY-E), myelin (MY-E) and mitochondria (MI-E) were obtained by sucrose density centrifugation. Rat liver (RL) was used for control antigens. Wheat-germ lectin affinity chromatography yielded membrane-enriched fractions of RBS, RL and whole rat brain (WRB). Antibody binding was examined by Western blotting. IgM reactivity was detected in 12/73 sera (16%) and was directed to proteins of 62K, 48K 37K molecular weight. IgG reactivity was present in 5/73 sera (7%) to proteins of 52K, 48K, 37K and 29K molecular weight. Except for binding to the 52K and 37K proteins these autoantibodies were not detected in control sera. Reactivity was usually absent, or present in reduced amounts, in WRB and RL. Additional experiments revealed that binding of IgM to 62K was found predominantly in SY-E and MY-E fractions, 48K in SY-E and MI-E fractions and 37K in the SY-E fraction. Binding of IgG to 48K and 29K was detected in the SY-E and MI-E, but reactivity to 52K and 37K was restricted to the SY-E fraction. Thus, sera from SLE patients contain antibodies to synaptosomal antigens that may contribute to the neuropsychiatric manifestations of the disease. PMID- 8485559 TI - Calprotectin in patients with systemic lupus erythematosus: relation to clinical and laboratory parameters of disease activity. AB - Calprotectin (L1) is a granulocyte and monocyte cytosolic protein released during activation of these cells. The plasma level of L1 has been shown to be a good marker of disease activity in rheumatoid arthritis. In this cross-sectional study of 100 patients with systemic lupus erythematosus (SLE), the serum level of L1 was found to be higher in patients than in matched controls (3661 micrograms/l versus 1051 micrograms/l; P < 0.001). The serum level of L1 was the only laboratory parameter with significant association to the disease activity index SLEDAI (r = 0.28; P < 0.01). Furthermore, the serum level of L1 was significantly higher in SLE patients with anti-DNA antibodies compared to patients without anti DNA antibodies (4501 micrograms/l versus 3279 micrograms/l; P = 0.01). SLE patients with arthritis had higher serum levels of L1 than patients without arthritis (7652 micrograms/l versus 2811 micrograms/l; P < 0.01), indicating that the serum level of L1 also reflects arthritis activity in SLE. PMID- 8485560 TI - Autoimmune thyroid disorders in SLE in Singapore. AB - One hundred and twenty-nine patients with systemic lupus erythematosus were screened for thyroid function tests. Of these, 8.9% had hyperthyroidism and 3.9% Hashimoto's thyroiditis. Euthyroid sick syndrome was present in 47.8% of patients. There was a high prevalence of antimicrosomal and antithyroglobulin antibodies (32.2%). Aberrations in thyroid function tests are common in SLE but the incidence of thyroid failure is low. PMID- 8485561 TI - Salmonella infection in systemic lupus erythematosus. AB - Patients with systemic lupus erythematosus (SLE) are susceptible to infections, notably salmonellosis. We report 37 cases of salmonella infection in 24 patients with SLE. These cases were detected in a group of 770 patients with SLE. All the patients were women, with a mean age of 25.6 years. At the onset of salmonella infection, 81% were taking prednisolone and 27% were taking cytotoxic drugs. Renal involvement was present in 75% of patients, which was approximately the same as in other SLE patients. Bacteremia, arthritis, osteomyelitis and rare manifestations of salmonellosis, including pulmonary and urinary tract involvement, were encountered. Diagnosis was based on isolation of the microorganism, mostly from blood cultures. Salmonella species other than typhi and paratyphi were often responsible. Widal agglutination test was positive in less than half the cases, and leukopenia was not seen frequently. Recurrence of infection in 29% of the patients and the high mortality rate (28.5%), despite the conventional period of appropriate antimicrobial treatment, show a poor prognosis of salmonellosis in SLE patients. This special picture of salmonellosis argues for a much longer period of treatment in these patients. PMID- 8485562 TI - Anticardiolipin syndrome, aspirin therapy and fetal malformation. AB - A patient with systemic lupus erythematosus and elevated cardiolipin antibody levels was given low-dose aspirin therapy prior to and throughout her third pregnancy to minimize the risk of miscarriage. She delivered a boy at 38 weeks with the skeletal deformity of two thoracic hemivertebrae. The putative role of aspirin causing this birth defect is discussed. PMID- 8485563 TI - Anti-Ro and lymphopenia in SLE. PMID- 8485564 TI - Refractory nephrotic syndrome in lupus nephritis: favorable response to indomethacin therapy. AB - The effects of indomethacin on urinary protein excretion, levels of serum albumin and renal function were studied prospectively in six patients with systemic lupus erythematosus (SLE) and refractory nephrotic syndrome due to lupus nephritis. Two had membranoproliferative glomerulonephritis, two had diffuse proliferative glomerulonephritis, and one each had mesangioproliferative and membranous glomerulonephritis. All experienced a considerable reduction in urinary protein excretion and an increase in serum albumin. Indomethacin was discontinued in two patients because of side effects, and proteinuria recurred to pretreatment levels. The decrease of proteinuria continued during long-term treatment in three patients. Indomethacin did not cause a permanent decline in renal function. Our results suggest that therapy with indomethacin may be beneficial for the treatment of refractory nephrotic syndrome in selected SLE patients. However, because of potential side effects the administration of indomethacin should be monitored closely. PMID- 8485565 TI - The relevance of antimalarial therapy with regard to thrombosis, hypercholesterolemia and cytokines in SLE. AB - Hydroxychloroquine has several less well-known actions that may have clinical relevance in treating systemic lupus erythematosus (SLE). (1) Hydroxychloroquine has a possible anti-thrombotic action. It is a platelet inhibitor and appears to decrease the risk of thromboembolism in patients with anticardiolipin antibodies. (2) Hydroxychloroquine is associated with lower serum cholesterol and low-density lipoprotein levels compared to those present in patients who are taking corticosteroids but not antimalarials for SLE. (3) It may also decrease abnormal levels of cytokines. Interleukin-6 (IL-6), soluble CD8 and soluble IL-2 receptors (sIL-2R) are lower in patients taking antimalarials compared to those on corticosteroids alone or on neither medication. Serum levels of CD8 and sIL-2R decrease after 6 weeks of hydroxychloroquine treatment. These findings may help explain the favorable response of SLE patients treated with antimalarials. PMID- 8485566 TI - Ophthalmologic safety profile of antimalarial drugs. AB - The ophthalmologic safety of antimalarial drugs is well established, but absolute safety cannot be assured. Three types of side effects may develop. Corneal deposits and neuromuscular-associated blurred vision are always reversible and therefore benign. Visual loss has occurred in patients with retinopathy. Retinopathy may be divided into true retinopathy and premaculopathy. It is true retinopathy that may be associated with visual loss, while premaculopathy consists of subtle visual field and funduscopic abnormalities. These premaculopathic changes are generally completely reversible with drug discontinuation and have not been shown to progress. Hydroxychloroquine appears safer than chloroquine when currently accepted equivalent doses are used. Fewer than 20 patients with true retinopathy caused by hydroxychloroquine have been reported; more patients have developed true retinopathy when taking chloroquine. The safety profile is most dependent on low daily dose and regular ophthalmologic monitoring. The optimal strategy of ophthalmologic testing has not yet been determined, but visual acuity, funduscopic examination and visual field examination should be monitored. Self-administered ophthalmologic testing with Amsler grids may contribute additional safety but is not a replacement for physician testing. PMID- 8485567 TI - Antimalarial drugs, pregnancy and lactation. AB - Disease activity has been demonstrated to be one of the major factors contributing to fetal loss in SLE patients, and discontinuation of antimalarial therapy can precipitate a flare of disease. It is therefore important to determine whether it is safe to continue antimalarial therapy throughout pregnancy. We have previously stated that we consider lupus patients and their fetuses to be at risk for disaster if antimalarial therapy is discontinued during pregnancy, and it has been our experience that lupus patients can produce normal offspring even if they are taking daily chloroquine or hydroxychloroquine. Several other reports now support our findings that it is probably safe to continue antimalarial therapy during pregnancy, although there are no large studies published. Data on the secretion of hydroxychloroquine in the breast milk of patients on steady-state hydroxychloroquine therapy are minimal, and further studies are required to determine whether these women can safely nurse their infants while taking hydroxychloroquine daily. PMID- 8485568 TI - The efficacy of antimalarials in systemic lupus erythematosus. AB - The use of antimalarial drugs to treat systemic lupus erythematosus (SLE) is reviewed regarding their value in SLE of mild-to-moderate disease activity, as corticosteroid-sparing agents, and as an adjunctive therapy in severe SLE. A retrospective controlled study of a variety of antimalarials and a randomized discontinuation trial of hydroxychloroquine support the considerable clinical belief that antimalarials are of benefit in mild-to-moderate SLE. Anecdotal reports and the opinion of experienced clinicians suggest that antimalarials permit the use of lower doses of corticosteroids. No controlled study has confirmed a corticosteroid-sparing role for antimalarials, although no controlled study has been conducted specifically to address this hypothesis. The data on antimalarials in severe SLE are scant. Antimalarials are likely effective in at least a subgroup of SLE patients with mild-to-moderate disease activity. Whether these agents are corticosteroid sparing and prevent severe disease exacerbations is unproven. Given the low toxicity of antimalarials, further studies are clearly warranted. PMID- 8485569 TI - Adding to the amyloidoses. PMID- 8485570 TI - Gene delivery into the brain using virus vectors. PMID- 8485571 TI - Finding new genes faster than ever. PMID- 8485572 TI - A medley of retinal dystrophies. PMID- 8485573 TI - Universal community carrier screening for cystic fibrosis? AB - Approximately 5% of the Caucasian North European and North American populations are carriers of the gene defect causing cystic fibrosis (CF). Since the CF gene was isolated in 1989 and the common mutations identified, there has been debate as to whether community-wide screening for CF carriers should be offered. Pilot studies and new discussions are leading to a consensus that screening is now possible and will not lead to undue anxiety, but there is still no agreement as to cost, or how it will be used by those screening positive. PMID- 8485574 TI - Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene. AB - Butterfly-shaped pigment dystrophy of the fovea is an autosomal dominant eye disease characterized by a bilateral accumulation of yellowish or pigmented material at the level of the retinal pigment epithelium. It shares some clinical and histopathologic features with age related macular degeneration which is the most common cause of legal blindness in older patients. We screened affected patients from a three generation family with butterfly dystrophy for mutations in candidate genes. A base substitution was identified in the peripherin (RDS) gene and DNA sequencing revealed a G to A transition in codon 167 that substitutes aspartic acid for a highly conserved glycine. The mutation segregates with the disease phenotype (Zmax = 4, theta = 0) strongly suggesting that it causes the macular disease in this family. PMID- 8485575 TI - A null mutation in the human peripherin/RDS gene in a family with autosomal dominant retinitis punctata albescens. AB - The murine rds (retinal degeneration slow) allele is a semidominant null allele that causes photoreceptor degeneration. The wild-type sequence at the rds locus encodes a photoreceptor disc membrane protein named peripherin/RDS. Mutations in the homologous human peripherin/RDS gene can cause autosomal dominant retinitis pigmentosa, but these are missense mutations or deletions of single codons. No obvious null alleles have been reported in humans, so that the human phenotype corresponding to rds is as yet unknown. Here we report a 2-basepair deletion in codon 25 of the human gene in a family with autosomal dominant retinitis punctata albescens, suggesting that this disease, rather than retinitis pigmentosa, is the comparable human phenotype. PMID- 8485576 TI - Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy. AB - Mutations in the RDS gene, which encodes the photoreceptor glycoprotein peripherin, have been sought in families with autosomal dominant retinal dystrophies. A cysteine deletion at codon 118/119 is associated with retinitis pigmentosa in one. Three families with similar macular dystrophy have mutations at codon 172, arginine being substituted by tryptophan in two and by glutamine in one. A stop sequence at codon 258 exists in a family with adult vitelliform macular dystrophy. These findings demonstrate that both retinitis pigmentosa and macular dystrophies are caused by mutations in RDS and that the functional significance of certain amino-acids in peripherin-RDS may be different in cones and rods. PMID- 8485577 TI - Transfer of a foreign gene into the brain using adenovirus vectors. AB - The ability of a replication-deficient adenovirus vector to transfer a foreign gene into neural cells of adult rats in vivo has been analysed. A large number of neural cells (including neurons, astrocytes and ependymal cells) expressed an E. coli lacZ transgene for at least 45 days after inoculation of various brain areas. Injecting up to 3 x 10(5) pfu in 10 microliters did not result in any detectable cytopathic effects--these were only observed for very high titres of infection (> 10(7) pfu 10 microliters-1). Adenovirus vectors therefore appear to be a promising means for in vivo transfer of therapeutic genes into the central nervous system. PMID- 8485578 TI - Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors. AB - To evaluate the potential for adenovirus-mediated central nervous system (CNS) gene transfer, the replication deficient recombinant adenovirus vectors Ad.RSV beta gal (coding for beta-galactosidase) and Ad-alpha 1AT (coding for human alpha 1-antitrypsin) were administered to the lateral ventricle of rats. Ad.RSV beta gal transferred beta-galactosidase to ependymal cells lining the ventricles whereas Ad-alpha 1AT mediated alpha 1-antitrypsin secretion into the cerebral spinal fluid for 1 week. These observations, together with beta-galactosidase activity in the globus pallidus and substantia nigra following stereotactic administration of Ad.RSV beta gal to the globus pallidus, suggest that adenovirus vectors will be useful for CNS gene therapy. PMID- 8485579 TI - Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. AB - The inherited disease Lesch-Nyhan syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan syndrome and the evaluation of novel therapies. PMID- 8485580 TI - Physical mapping of the holoprosencephaly critical region on chromosome 7q36. AB - Holoprosencephaly (HPE) is a developmental field defect involving the brain and face. Cytogenetic deletions in patients with HPE have localized one of the HPE genes to chromosomal region 7q36. We have characterized the 7q deletions in thirteen HPE patients. The result is the construction of a high resolution physical map of 7q32-qter. As a first step towards cloning an HPE gene crucial for normal brain development, we have defined the HPE minimal critical region in 7q36 between D7S292 and D7S392. PMID- 8485581 TI - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has been recently reported as a cause of stroke. It is characterized, in the absence of hypertension, by recurrent subcortical ischaemic strokes, starting in early or midadulthood and leading in some patients to dementia. Magnetic resonance imaging and pathological examination show numerous small subcortical infarcts and a diffuse leukoencephalopathy underlaid by a non-arteriosclerotic, non-amyloid angiopathy. We performed genetic linkage analysis in two unrelated families and assigned the disease locus to chromosome 19q12. Multilocus analysis with the location scores method established the best estimate for the location of the affected gene within a 14 centimorgan interval bracketed by D19S221 and D19S222 loci. PMID- 8485582 TI - A de novo pathological point mutation at the 21-hydroxylase locus: implications for gene conversion in the human genome. AB - More than two hundred characterized 21-hydroxylase deficiency alleles appear to result exclusively from sequence exchanges involving the 21-hydroxylase gene (CYP21B) and a closely related pseudogene (CYP21A). Gene conversion-like events have also been reported in many other human gene clusters, but in the absence of a de novo mutation, the alternative explanation of a multiple recombination is possible. We now report a de novo pathological mutation at the 21-hydroxylase locus. DNA sequence analysis suggests that the mutation arose by a microconversion event involving exchange of up to 390 nucleotides between maternal CYP21A and CYP21B genes. This putative de novo gene conversion event appears to be the first characterized in humans. PMID- 8485583 TI - Identification of protein coding regions by database similarity search. AB - Sequence similarity between a translated nucleotide sequence and a known biological protein can provide strong evidence for the presence of a homologous coding region, even between distantly related genes. The computer program BLASTX performed conceptual translation of a nucleotide query sequence followed by a protein database search in one programmatic step. We characterized the sensitivity of BLASTX recognition to the presence of substitution, insertion and deletion errors in the query sequence and to sequence divergence. Reading frames were reliably identified in the presence of 1% query errors, a rate that is typical for primary sequence data. BLASTX is appropriate for use in moderate and large scale sequencing projects at the earliest opportunity, when the data are most prone to containing errors. PMID- 8485584 TI - Predicting the cytochrome P450 mediated metabolism of xenobiotics. AB - The cytochrome P450s play a unique role in the metabolism of xenobiotics. Characteristics which allow a vast number of foreign compounds to be metabolized by a limited number of enzymes include broad substrate specificity and broad regioselectivity. Because of their importance in both the metabolism and toxicity of drugs and environmental contaminants, efforts are being made to use computational methods to predict these biotransformation pathways. This review describes the recent progress towards the prediction of the tertiary structures of the various P450s and the determination of the electronic characteristics of substrates which determine their tendency to be oxidized by the P450s. PMID- 8485585 TI - Characterization of a human cell line expressing high levels of cDNA-derived CYP2D6. AB - We have developed a human B-lymphoblastoid cell, designated h2D6v2, which expresses high levels of CYP2D6 cDNA. Microsomal P450 contents of 160 pmol mg-1 protein were observed. NADPH-fortified microsomes exhibited a substantial capacity to hydroxylate the prototype CYP2D6 substrates bufuralol and debrisoquine. Kinetic parameters, apparent Km, turnover number, Ki for quinidine inhibition and stereospecificity of bufuralol hydroxylation, observed with the human lymphoblast expressed enzyme were similar to those observed in human liver microsomes or purified liver CYP2D6 proteins. Therefore, the human lymphoblast expressed material appears to faithfully reflect the authentic protein. Relative to control cells, h2D6v2 cells were more sensitive to the cytotoxicity and mutagenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), supporting our previous observation with a cell line expressing lower levels of CYP2D6. h2D6v2 microsomes were capable of metabolizing NNK and NNK metabolism and mutagenicity were markedly inhibited by the addition of quinidine, a CYP2D6 inhibitor. h2D6v2 cells coupled with control cells, represent a useful in vitro system for studying xenobiotic metabolism by the clinically important, polymorphic CYP2D6. The human lymphoblast system offers the desirable ability to couple metabolic transformation studies with toxicological endpoints such as cytotoxicity and mutagenicity. PMID- 8485586 TI - Molecular genetics of the flavin-dependent monooxygenases. PMID- 8485587 TI - Utilizing urinary metabolite data in studying the variability of acetaminophen metabolism. PMID- 8485588 TI - [The active forces of continence. Illustration by quantified analysis of the electromyographic signal of the urethral striated sphincter combined with urethral pressure studies]. AB - Continence in women, ensured by a constantly positive urethral closing pressure, is the result of two phenomena: purely passive factors (urethral pressure and compliance, transmission of bladder pressure to the urethra) and active factors mediated by a voluntary and reflex neuromuscular mechanism (contraction, reflexivity, sphincter endurance). In order to define these active forces of continence, we simultaneously studied the quantitative electromyographic activity of the striated sphincter and the bulbocavernosus muscle and variations in the urethral and vesical pressure under various conditions (rest, coughing, stimulation of the pudendal nerve). During coughing, the urethral pressure peak occurred earlier (100 milliseconds) than the vesical peak, associated with hypertransmission of 20%, the bulbocavernosus muscle contracted first, followed by contraction of the striated urethral sphincter (150 ms delay) and this electrical activity preceded the rise in vesical and urethral pressures. Stimulation of the pudendal nerve eliminated the possibility of an artefact related to coughing and induced the same sequence of events. PMID- 8485589 TI - [Bladder sparing in infiltrating tumors of the bladder: a reasonably sound option?]. PMID- 8485590 TI - [Decreased urethral pressure after coughing: the concept of urethral fatigability. Its relationship with active forces of continence]. AB - The existence of urethral fatiguability was demonstrated by a sphinctometric study in 30 women. Comparison of the baseline urethral pressure values and after 6 maximal coughs demonstrated a mean reduction in urethral pressure of 40% (range: 24.5 to 90%) in 10 out of 18 women with stress incontinence. This decreased pressure lasted for several seconds. Spectral analysis of the electromyographic recording of the striated urethral sphincter under basal conditions and then after coughing confirmed the intervention of the striated and periurethral musculature with a marked quantitative decrease in the electrical activity of the sphincter. The clinical pathophysiological, prognostic and therapeutic implications of this new concept are discussed. PMID- 8485591 TI - [Treatment of interstitial cystitis with sub-trigonal cystectomy and enterocystoplasty]. AB - Eight patients with interstitial cystitis were treated by supratrigonal cystectomy and enterocystoplasty. The indications for this procedure are functionally disabling interstitial cystitis refractory to conservative treatment and associated with severely altered cystomanometric parameters. 6 patients obtained an excellent functional result and 2 patients obtained a poor result, due to sphincter hypotonia responsible for total incontinence in one case. PMID- 8485592 TI - [Value of elective cure of fibrodysplastic aneurysms of the renal artery in hypertensive patients]. AB - Renal artery aneurysms (RAA) are rare lesions, often associated with hypertension. In order to evaluate the benefit in terms of blood pressure of elective cure of a fibrodysplastic renal artery aneurysm in hypertensive patients, 22 patients were studied retrospectively. With a mean follow-up of 66 months, correction or improvement of hypertension was obtained in all patients with an isolated aneurysm or an aneurysm associated with haemodynamic lesions of the renal artery, treated at the same time, but only 40% of cases when the aneurysm was associated with non-heamodynamic lesions. Direct criteria attributing the hypertension to the aneurysm were generally absent. PMID- 8485593 TI - [Color echo-doppler of the ureterovesical stream. Normal aspects. Application to the acute ureteral obstruction]. AB - A colour Doppler ultrasound study of the ureterovesical was performed to define the normal features, variants and abnormalities of the ureteric stream by comparing 50 normal subjects and 19 subjects with renal colic due to ureteric stones. The examination included assessment of the frequency, intensity, morphology and symmetry of the ureterovesical stream. In normal subjects, the stream was either absent, especially in the case of fluid restriction (36%), present and symmetrical (34%) or asymmetrical (30%). In patients with ureteric stones, during a non-painful period and in the absence of obstruction on IVU, the stream was normal and symmetrical (9%) while during a painful period with obstruction on IVU, the ureteric stream was either absent (47%) or abnormal and asymmetrical (31%). A continuous stream, very suggestive of obstruction, was observed in 5 cases. Colour Doppler ultrasound is a new, simple method which may be helpful in the diagnosis of renal colic, particularly in cases in which the pyelocaliceal cavities are not dilated. PMID- 8485594 TI - [Extracorporeal lithotripsy or ureteroscopy for the treatment of calculi of the lower ureter]. AB - Two therapies, ureterolithotripsy (URL) and extracorporeal shock wave lithotripsy (ESWL) can be used in the treatment of lower ureteral calculi. In a retrospective analysis ureterolithotripsy and extracorporeal shock wave lithotripsy for lower ureteral calculi were compared to evaluate morbidity. During a 3 year period 161 patients treated with ureterolithotripsy and 71 who underwent extracorporeal shock wave lithotripsy (Siemens Lithostar) were analysed as to the success rate, effectiveness quotient, complication rate and length of hospitalization. Followup consisted of ultrasound and a plain film of the kidneys, ureteres and bladder 1 day and 1 to 3 months postoperatively. Complete removal of all stone fragments was achieved in 95.5% of the patients treated endourologically with a 1.2% retreatment rate. In the group treated with extracorporeal shock wave lithotripsy success rate was 82.1% with a 19.6% retreatment rate. Among the patients who underwent ureteroscopy and stone removal 16.1% had complications compared to 10.7% in the ESWL group. The mean stone diameter was 0.8 cm in the endourological group and 0.7 cm in the ESWL group. Stone size was not a determining factor for the stone free rate and effectiveness quotient in the patients treated endourologically. Indeed, in patients who underwent ESWL for large stones the stone-free rate and effectiveness quotient decreased to 78.9% and 57.7%. Ureterolithotripsy will continue to have a primary role in the management of lower ureteral stones. As extracorporeal shock wave lithotripsy is an effective noninvasive procedure, requiring no anesthesia and hospitalization as routine, it may be considered an alternative either primarily or after failed ureteroscopy. PMID- 8485595 TI - [Surgical cure of anomalies of the pyelo-ureteral junction with posterior vertical lumbar excision: report of 25 cases]. AB - Posterior vertical lumbar (PVL) incision does not involve any muscle or nerve section. It is minimally painful, does not give rise to incisional hernias and reduces the hospital stay. Pyeloplasty for cure of the ureteropelvic junction (UPJ) is a good indication, as this incision provides access to the renal pelvis without renal mobilisation and without interference by the vascular pedicle and allows a more superficial operative field. This retrospective study is based on 25 PVL incisions performed between 1979 and 1992 in 24 patients (15 females and 6 males with a mean age of 31.8 years) on the left kidney in 11 cases, right kidney in 12 cases and bilaterally in 1 case. No intraoperative complications were observed. The anastomosis was stented with a Gil-Vernet ureteronephrostomy tube for an average of eight days in every case. Early complications (< or = 1 month) consisted of six cases of fever, one wound abscess and one urinary fistula. Normal feeding was always rapidly restored. Long-term follow-up did not reveal any incisional hernias, but two cases of recurrence (8%), two cases of stones and one case (4%) of refractory neuralgia (> or = 6 months) in the territory of the ilioinguinal nerve. In this indication, there is no gain in terms of hospital stay due to the need to maintain the ureteronephrostomy tube for at least five days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485596 TI - [Hydatid cyst of the kidney. Contribution of imaging techniques]. AB - The authors report a case of renal hydatid disease, a rare disease in France. After reviewing the recent data of the literature, they stress the value of computed tomography and especially MRI in the presumptive diagnosis. PMID- 8485597 TI - [Supernumerary urethras in men. Report of supernumerary blind epispadias]. AB - Supernumerary urethra, a rare anatomical anomaly, can be explained by various embryological theories, accounting for the multitude of classifications proposed. Its diverse, minor or very severe clinical manifestations suggest the diagnosis, which is confirmed by retrograde and voiding cystourethrography. Treatment is surgical or, more rarely, endoscopic. PMID- 8485598 TI - [Ectopic prostatic polyp in the bladder. Report of 2 cases]. AB - An ectopic prostatic polyp situated in the bladder is a rare cause of terminal haematuria. The authors present an extensive review of the literature concerning this lesion which must be recognised not only by histologists, responsible for establishing the diagnosis, but also by urologists, who must be aware of its benign nature. PMID- 8485599 TI - [Review of phase III clinical trials on combined anti-androgen therapies in patients with metastasized prostatic cancer]. PMID- 8485600 TI - [Neuroendocrine cancers of the prostate]. AB - This article is a transcription of several papers on neuroendocrine cancers of the prostate presented to the Uropathology Club in Angers in 1990. It consists of three parts: Firstly, a study of neuroendocrine cells in various organs of the human body, followed by the demonstration of these cells in the normal and pathological prostate. The second part reports 3 cases of neuroendocrine cancers as they are observed in routine practice. A total of 66 cases of pure neuroendocrine cancers have been reported to date in the English language literature. This type of cancer is characterised by a rapid, hormone-resistant course with the development of multiple metastases, frequently visceral. Periods of remission in response to chemotherapy may be observed in some cases. The third part concerns the systematic demonstration of neuroendocrine cells in prostatic adenocarcinoma. The percentage of neuroendocrine cells demonstrated by various histological techniques is directly correlated to an increasingly severe prognosis of the cancer. PMID- 8485601 TI - [Interstitial cystitis]. AB - Interstitial cystitis, described for many years, remains a mystery for several reasons. Although the clinical and therapeutic understanding of this disease have improved, the histological features are non-specific and the pathogenesis is still unclear. The aim of this article is to briefly review the current state of knowledge and to remind the reader that this disease must not be underestimated or ignored. PMID- 8485602 TI - Management of cataract in adults. Agency for Health Care Policy and Research. PMID- 8485603 TI - Depression in primary care: detection, diagnosis, and treatment. Agency for Health Care Policy and Research. PMID- 8485604 TI - Sickle cell disease: comprehensive screening and management in newborns and infants. Agency for Health Care Policy and Research. PMID- 8485605 TI - Maternal characteristics of women delivered of twins: natural vs. induced. AB - This study retrospectively compared sociodemographic and anthropometric data, as well as selected obstetric outcomes, of 13 mothers of twins who conceived after ovulation induction with clomiphene citrate or Pergonal with similar data from 255 mothers who conceived naturally. Infertile women were significantly (P < .011) older and likely to be married, of the white race, and more educated than women who conceived naturally. Treated women were also taller and heavier prior to conception (NS). Treated women gained significantly more weight (45.9 lb vs. 30.1 lb). They also had a higher proportion of gestations > 32 weeks (91.7% vs. 74.1%) and longer mean gestations (36.5 weeks vs. 35.4 weeks) compared to naturally conceiving mothers of twins, but neither of these differences was significant. The infants of treated mothers had birthweights 9.5% heavier than the infants of mothers who conceived naturally. These retrospective findings suggest that previously infertile women who conceive twins do not suffer worse reproductive outcome than women who conceive naturally. PMID- 8485606 TI - Does ovulation stimulation improve fertility in women with minimal/mild endometriosis after laser laparoscopy? AB - Cycle fecundity was retrospectively analyzed in a group of infertile women after minimal/mild endometriosis had been treated by carbon dioxide laser laparoscopy. Patients were followed in spontaneous (observation) cycles as well as in treatment cycles using ovulation stimulation. Treatment protocols included clomiphene citrate (CC), sequential CC/human menopausal gonadotropins/human chorionic gonadotropin (CC/hMG/hCG), and hMG/hCG. Some patients who failed to conceive with ovulation stimulation protocols underwent in vitro fertilization (IVF). Eighty-nine patients were followed for a total of 605 cycles, during which 37 pregnancies occurred. Cycle fecundity was 0.028 in observation cycles, and was higher with the use of CC (0.066), and significantly higher (P < .05) with use of CC/hMG/hCG (0.114) and hMG/hCG (0.073). The highest cycle fecundity was attained in IVF cycles (0.222). This retrospective analysis suggests that active ovulation management in patients with minimal/mild endometriosis treated by carbon dioxide laser laparoscopy may significantly increase cycle fecundity. PMID- 8485607 TI - Comparative efficacy of gestrinone and danazol in infertile women with endometriosis. AB - The relationship between endometriosis and infertility is observed frequently. Patients with both conditions require a conservative approach to their management. Since hormonal therapy is one of those approaches, we sought to compare the efficacy of Danazol and Gestrinone in 80 infertile patients (48 and 32, respectively). Therapy lasted 6 months in both treatment groups, and all patients studied had laboratory tests performed and were clinically evaluated and classified through laparoscopy before and after therapy. The improvement of symptoms and favorable follow-up were similar with both treatments. The reestablishment of menstrual patterns and fertility were also nearly alike in both groups. However, Gestrinone was associated with fewer secondary effects and is easier to administer than Danazol. We conclude that Gestrinone is a useful medication in the management of the infertile patient with endometriosis. PMID- 8485608 TI - Treatment of infertility patients with hMG-IUI in a private practice. AB - Between December 1988 and September 1990, 132 patients were treated with 432 cycles of superovulation with hMG and timed IUI for various infertility subgroups in a private office setting. All patients had a complete infertility evaluation, including semen analysis, postcoital testing, hysterosalpingogram, endometrial biopsy and laparoscopy, and immunological testing in most cases. Abnormal factors were treated by conventional surgical and/or medical means. Most patients had at least a 6-month trial at achieving normal conception prior to hMG-IUI therapy. Patients received up to six cycles of treatment. Forty-five patients (34%) are still under treatment; thus far, the overall pregnancy rate is 58 of 132 or 44%. Of the 58 pregnancies, there were 13 abortions (22.5%) and two ectopic pregnancies (3.5%). The pregnancy rate per cycles has been 58/432, or 13.5%. The on-going pregnancy rate is 43/132, or 32.6%, or 32/432 (10%) per cycle. Treatment with hMG-IUI seems to approach that for IVF for most conventionally treated infertility subgroups. It can be done at a much lower cost per cycle, thus allowing a greater number of couples the availability of treatment. The authors suggest that most infertility patients be offered hMG-IUI therapy prior to IVF referral. PMID- 8485609 TI - Measurement of placental protein 14 (PP14) not helpful in predicting infertility or spontaneous abortion. AB - Placental protein 14 (PP14) can be measured in the serum by radioimmunoassay. The level rises from mid to late luteal phase in a manner similar to the endometrial biopsy. A study was initiated to determine if a clinical association could be found between the late luteal phase serum PP14 level and subsequent pregnancy and spontaneous abortion rate. No difference was found in the preconception PP14 level in patients conceiving versus those not conceiving, nor in those aborting versus those not aborting. A trend toward higher levels in conception versus non conception cycles was noted, but a large patient group will be needed to demonstrate statistical significance. PMID- 8485610 TI - Risk factors in men and women consulting for infertility. AB - In three regions of France, over a period of 1 year, we registered all couples (women and men) who have consulted and obtained a medical evaluation (medical causes and risk factors) for primary or secondary infertility. For women with secondary infertility caused by tubal disorders (compared to other causes) the risk factors are: STDs (RR = 7.5; 4.8-11.6); previous surgery, including appendectomy (RR = 4.7; 3.4-6.5); history of salpingitis (RR = 32.1; 18.8-55.3); and ectopic pregnancy (RR = 21.5; 11.4-41.3). For consulting men, secondary infertility risk factors are varicocele (RR = 4.1; 2.0-8.5) and previous genital infection (RR = 5.8; 2.8-11.7) for oligoteratosasthenospermia, and histories of major treatment or exposure to toxic agents such as X-rays, benzenes, or pesticides (RR = 6.6; 1.3-30.4) for secretory azoospermia. These results underline the importance for physicians of making a systematic exploration for all the different infertility risk factors in men and women, enabling greater control and effectiveness in medical diagnosis. PMID- 8485611 TI - Psychological sequelae of surgical reversal or of IVF after tubal ligation. AB - This study investigates the psychological concomitants and sequelae of surgical reversal (tubal reanastomosis) or of IVF after tubal ligation. We held semi structured interviews and used the Giessen test and the Strauss-Appelt body image questionnaire. The sample comprised 25 women; a new partner was the leading reason for reversal in 16 cases ('New Partner'), while in 9 cases experiences of loss (of a child or of ideal values) prevailed ('Loss'). The two groups differed in a number of relevant demographic and psychological data. 'New Partner' patients showed a pattern of factors known to be associated with regret of sterilization. 'Loss' women were less satisfied with reversal than 'New Partner' subjects (P < .01). Satisfaction with reversal was independent of an achieved pregnancy. Patients considered surgical reversal to be preferable to IVF because of the "restoration of the mutilation." In the Giessen test, 'New Partner' women were more depressive (P < .05) and more submissive (P < .05) than 'Loss' subjects. Cluster analysis of the whole sample revealed four well distinguishable profiles. 'Loss' patients experienced less insecurity of their body image than both 'New Partner' women and the general female population. We conclude that reversal of sterilization helps to restore body-image and self-esteem, but it may counteract mourning. Consequences for pre-reversal counseling are discussed. PMID- 8485612 TI - A randomized study to compare the effectiveness, tolerability, and acceptability of two different transdermal estradiol replacement therapies. The Transdermal HRT Investigators Group. AB - This randomized trial was designed to assess the efficacy, tolerability, and acceptability of two different transdermal estradiol replacement therapies: Cilag Estradiol-TTS (a matrix system) and Ciba-Geigy Estradiol-TTS (a reservoir system). Five hundred and fourteen patients were evaluable for efficacy, and all patients who had received the study medications were evaluated for safety (n = 530). Both treatments significantly improved systemic and urogenital symptoms as evidenced by a decrease in the number of hot flushes and the Kupperman Index score; there was no difference in effectiveness between the two treatments. Safety evaluation revealed a low incidence of adverse events, mainly compatible with exogenously administered estrogen and progestagen. Endometrial biopsies at the end of treatment were similar between groups and consistent with balanced hormone replacement therapy. Analyses of acceptability data revealed a low incidence of skin reactions and an added benefit with the Cilag-Estradiol-TTS patch in terms of convenience owing to the adhesiveness of the patch. In conclusion, both transdermal estradiol replacement therapies were effective and well tolerated in the treatment of postmenopausal estrogen deficiency symptoms, and the Cilag Estradiol-TTS patch had an advantage in terms of convenience and adhesiveness. PMID- 8485613 TI - Gonadotropin-releasing hormone has a biphasic action on aromatase activity through protein kinase C in granulosa cells. AB - Gonadotropin-releasing hormone (GnRH) exerts direct effects on the ovary by binding to its specific receptor, and stimulates inositol phospholipid turnover in granulosa cells. This study was undertaken to determine the involvement of protein kinase C in the action of GnRH on follicle-stimulating hormone (FSH) stimulated aromatase activity in rat granulosa cells. The aromatase activity was examined by conversion of exogenously supplied androstenedione to estrogen. FSH stimulated aromatase activity, with a low rate of estrogen production for the first 18 hours, followed by a high rate of production on further incubation. Addition of GnRH potentiated the aromatase response to FSH in the first 18 hours, but caused a dose-dependent inhibition of the FSH-stimulated aromatase activity from 20 to 45 hours of incubation. Half-maximal effects of GnRH occurred at 10 nM. Both of the biphasic actions of GnRH on aromatase response to FSH were mimicked by protein kinase C activators, phobol myristate acetate (PMA) and oleoylacetyl glycerol; maximal effects occurred at 1 to 10 ng/mL. When the cells were exposed first to FSH for 18 hours and then to PMA, the second phase of estrogen production was also suppressed. The second phase, producing quantitative estrogen, might result from induction of the enzyme, because cycloheximide (100 ng/mL) prevented the FSH-induced activation of aromatase from 20 hours of incubation. These results indicate that the biphasic actions of GnRH on FSH stimulated aromatase activity are mediated by protein kinase C. The inhibitory action of GnRH on quantitative steroidogenesis caused by prolonged FSH stimulation might be expressed through the impaired induction of aromatase. PMID- 8485614 TI - Analysis of oviduct-derived embryonic growth stimulator activity. AB - A co-culture study was carried out using primary cultures of hamster oviduct tissues to analyze oviduct-derived embryonic growth stimulating factor. In co cultures of mouse pronuclear embryos and hamster oviduct tissue, the 4-cell rate after 48 hours (53.2%, 109/205) and blastocyst rate after 96 hours (22.4%, 46/205) were significantly higher than those of the standard culture group (4 cell rate, 41.8%, 76/182; blastocyst rate, 4.4%, 8/182), suggesting an embryonic growth stimulating effect of the co-culture. Similar effects were observed in co cultures of both 2-cell mouse embryos collected 40 or 48 hours after the hCG administration and morulae collected 64 hours after hCG, but no such effect was observed in co-cultures of hamster embryos. When mouse embryos were cultured in a conditioned medium, which was the supernatant of the hamster oviduct tissue culture in Biggers-Whitten-Whittingham's (BWW) solution, no embryonic growth stimulating effect was observed. Further, no stimulating effect was observed in the conditioned medium obtained from 24-hour co-cultures of embryos and oviduct tissue. From these results, we considered the embryonic growth stimulating factor to be labile, with concentration-dependent effects. The absence of a stimulatory effect of co-culturing on the growth of hamster embryos also suggests the presence of species variations in the in vitro arrest of embryogenesis. PMID- 8485615 TI - Regulation of neural responses in the canine pyloric sphincter by opioids. AB - 1. Regulation of excitatory and inhibitory junction potentials (e.j.ps and i.j.ps) by opioid peptides was studied in isolated muscle strips from the pyloric sphincter of the dog. 2. Methionine enkephalin (MetEnk; 10(-10) to 10(-6) M) and [D-Ala2, D-Leu5] enkephalin (DADLE; 10(-11) to 10(-7) M), a delta-specific opioid agonist, inhibited i.j.ps and e.j.ps recorded from cells in the myenteric and submucosal regions of the circular muscle layer. These compounds had no effect on resting potential or slow wave activity suggesting that the effects on junction potentials were not due to direct effects on smooth muscle cells. 3. MetEnk and DADLE caused similar effects on junction potentials in preparations in which the myenteric plexus was removed, suggesting that opioids inhibit pre-junctional effects on nerve fibres within the muscularis externa. 4. Inhibition of junction potentials by MetEnk and DADLE was blocked by approximately the same extent by naloxone (10(-6) M) and ICI 174,864 (10(-6) M), a delta-specific antagonist. 5. MetEnk and DADLE blocked a portion of the i.j.p. that was sensitive to arginine analogues; after treatment with N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), MetEnk and DADLE had no further effect on i.j.ps. These data suggest that opioids regulate nitric oxide-dependent neurotransmission. 6. Naloxone (10( 6) M) alone had no effect on i.j.ps elicited by short trains of electrical field stimuli. 7. I.j.p. amplitude was reduced after a period of conditioning stimulation (2 min, 30 Hz, 30 V). Naloxone blocked the post-stimulation inhibition. Repetitive stimulation at high frequencies (30 Hz) resulted in sustained hyperpolarization. Naloxone increased the amplitude of the hyperpolarization responses elicited by high frequency stimulation.8. These results show that e.j.ps and i.j.ps in the canine pylorus are inhibited by opioids. A portion of the inhibitory effects appears to be mediated via delta receptors.9. Although pyloric muscles are richly innervated by nerves containing opioid peptides, brief trains of stimuli do not appear to release concentrations of opioids that are effective in regulating junction potentials. Higher frequency stimulation (or longer durations of stimulation) appear to be necessary to release concentrations of opioids that are effective in modulating the amplitude of junction potentials. PMID- 8485616 TI - Evidence for a nucleotide receptor on adrenal medullary endothelial cells linked to phospholipase C and phospholipase D. AB - 1. We have investigated whether the 'atypical' P2-purinoceptor previously described on adrenal microvasculature endothelial cells is a nucleotide receptor (responds to pyrimidines and purines) and is linked to phospholipase D as well as phospholipase C. 2. Cultured bovine adrenal medullary endothelial (BAME) cells responded to the pyrimidine UTP, as well as the purines. The total [3H]-inositol phosphate responses were with a rank order of UTP > ATP- = adenosine 5'-O-(3-thio triphosphate) (ATP gamma S) >> 2MeSATP. The selective P2x agonist beta, gamma methylene ATP was inactive. 3. Construction of dose-response curves to ATP, ATP gamma S and UTP in the presence and absence of additional agonists showed that responses to ATP gamma S and UTP were not additive, nor were those to UTP and ATP. This suggests that purines and pyrmidines acted via a common nucleotide receptor. 4. 32P-labelled BAME cells, in the presence of butanol, produced [32P] phosphatidylbutanol (PBut) when stimulated with ATP gamma S or the protein kinase C activator, tetradecanoyl phorbol acetate (TPA). 5. Cells labelled with [3H] palmitate and stimulated in the presence of butanol generated [3H]-PBut with the same order of agonist potencies seen for inositol phosphate responses. 6. The protein kinase C inhibitor, Ro 31-8220, abolished TPA and agonist stimulation of [3H]-PBut production. 7. These observations, and our related studies on bovine aortic endothelial cells, provide the first demonstration of a phospholipase C linked nucleotide receptor on vascular endothelial cells. It is concluded that BAME cells express a nucleotide receptor linked to phospholipase C and phospholipase D, but that activation of phospholipase D is probably down-stream of phospholipase C. PMID- 8485617 TI - Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats. AB - 1. The effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity were investigated in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats, fed a high fat-high cholesterol diet. 2. In high fat-high cholesterol (HF-HC) diet fed WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE) by reducing the low density lipoprotein (LDL) fraction, and reductions in total plasma triglyceride (TG) by reducing the very low density lipoprotein (VLDL) fraction. 3. Dicentrine therapy was associated with increased high density lipoprotein (HDL)-cholesterol levels; thus the ratio of total plasma cholesterol to HDL-cholesterol was improved. 4. In HF-HC diet fed conscious WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) also evoked dose-related decreases in mean arterial pressure (MAP) which were of greater magnitude in SH rats. Neither dose of dicentrine caused a significant change in heart rate (HR). 5. The aortic arches from SH rats fed the HF-HC diet for 8 weeks were significantly more affected by the atherosclerotic lesions than the abdominal aortae and renal arteries of WKY and SH rats. Oral administration of dicentrine (5 and 10 mg kg-1) for 4 weeks did not diminish the atherosclerotic lesion areas in WKY and SH rats. 6. In aortae of the hyperlipidaemic rats, significantly attenuated EC50 values and augmented maximal responses for phenylephrine-induced contraction were obtained. Endothelium dependent relaxation to acetylcholine was abolished, while endothelium independent relaxation to nitroprusside was well preserved. Dicentrine therapy caused significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction in hyperlipidaemic rats. However, dicentrine neither prevented the impaired relaxation to acetylcholine, nor affected the relaxation to nitroprusside during atherosclerosis progression.7. It is concluded that dicentrine decreases MAP, plasma CE, LDL-CE, plasma TG, VLDL-TG,vascular hyperreactivity to phenylephrine and increases HDL-CE levels. Dicentrine may thus hold potential for the reduction of two of the major risk factors, hypertension and hyperlipidaemia, for cardiovascular disease. PMID- 8485618 TI - Effects of nifedipine and ryanodine on adrenergic neurogenic contractions of rat vas deferens: evidence for a pulse-to-pulse change in Ca2+ sources. AB - 1. The effects of nifedipine and ryanodine on the adrenergic component of neurogenic contractions of the rat isolated vas deferens were studied in an attempt to identify the sources of Ca2+ mediating the contraction. The tissue was electrically stimulated by single pulses or pairs of widely spaced pulses. The purinergic component of contraction was suppressed by the presence of 300 microM suramin. 2. In Mg(2+)-free medium, nifedipine (0.01-10 microM) reduced the first and, to a greater extent, the second twitch elicited by two pulses 3 s apart. This pattern of inhibition was observed both in the absence of rauwolscine (when twitch 2 was smaller than twitch 1) and in the presence of 0.1 microM rauwolscine (when, due to interruption of prejunctional alpha 2-adrenoceptor-mediated autoinhibition, twitch 2 was of similar height to twitch 1). Nifedipine reduced only twitch 2 but not twitch 1 in medium containing 1.2 mM Mg2+. 3. Single pulses of increasing current strength elicited increasing contraction. Nifedipine reduced contractions by about the same absolute extent at all current strengths, so that the relative contribution of the nifedipine-sensitive component decreased with increasing current strength. 4. When the pulse interval in a pair was increased from 5 to 60 s, the inhibition by nifedipine of the second twitch was most marked at an interval of 5 s and declined as the interval increased. 5. In contrast to nifedipine, 20 microM ryanodine reduced the first twitch of a pair to a greater extent than a second twitch 5 s later, so that twitch 2 became greater than twitch 1. The inhibition by ryanodine of twitch 2 increased with increasing pulse interval.6. In vasa deferentia preincubated with [3H]-noradrenaline, I microM nifedipine and 20 microM ryanodine did not change the electrically evoked overflow of tritium, whereas 10 microM nifedipine increased it.7. It is concluded that, when the sympathetic axons of the vas deferens are stimulated by a single pulse(or the first pulse of a pair) in Mg2+-free medium, both Ca2+ mobilization inside the smooth muscle cells and Ca2+ entry contribute to the ensuing adrenergic contraction. The relative contribution of Ca2+ entry is small at maximal stimulus strength but increases with decreasing stimulus strength. When a second pulse follows the first after an appropriate interval, a switch of Ca2+ sources occurs: intracellular Ca2+mobilization is decreased during twitch 2, whereas Ca2+ entry is increased. PMID- 8485619 TI - Cellular mechanism of U78517F in the protection of porcine coronary artery endothelial cells from oxygen radical-induced damage. AB - 1. The aim of this study was to clarify the role of lipid peroxidation in cellular injury as assessed by lactate dehydrogenase (LDH) release from cultured coronary artery endothelial cells of the pig. Cells exposed to H2O2 at concentrations of 0.1 to 20 mM or to a xanthine and xanthine oxidase (X/XO) reaction mixture released LDH into the medium. Significant release from X/XO treated cells took place with a delay of 2 h. 2. Superoxide dismutase (SOD), catalase or dimethylthiourea attenuated the release of LDH from X/XO-treated cells. Similarly the putative inhibitor of lipid peroxidation, U78517F attenuated the release of LDH by X/XO with an IC50 of 0.08 microM. 3. H2O2 was continuously produced by the addition of X/XO to the medium alone. However, in the presence of endothelial cells, H2O2 was eliminated at 1 h. U78517F had no effect on either process. 4. The oxygen radical-induced release of LDH was associated with malondialdehyde (MDA) formation. U78517F inhibited the formation of MDA with an IC50 of 0.27 microM. 5. Reduction of the Ca2+ concentration in the incubation medium from 1.6 mM to 0.016 mM markedly attenuated the release of LDH from endothelial cells. Nifedipine (1 microM) did not attenuate the LDH release from the cells. 6. It is likely that porcine coronary artery endothelial cells can be thus injured by oxygen radicals presumably through hydroxyl radicals formed and consequent lipid peroxidation, and that the extracellular Ca2+ concentration plays an important role in the genesis of such endothelial cell damage. PMID- 8485620 TI - Ap4A and ADP-beta-S binding to P2 purinoceptors present on rat brain synaptic terminals. AB - 1. Diadenosine tetraphosphate (Ap4A) a dinucleotide stored and released from rat brain synaptic terminals presents two types of affinity binding sites in synaptosomes. When [3H]-Ap4A was used for binding studies a Kd value of 0.10 +/- 0.014 nM and a Bmax value of 16.6 +/- 1.2 fmol mg-1 protein were obtained for the high affinity binding site from the Scatchard analysis. The second binding site, obtained by displacement studies, showed a Ki value of 0.57 +/- 0.09 microM. 2. Displacement of [3H]-Ap4A by non-labelled Ap4A and P2-purinoceptor ligands showed a displacement order of Ap4A > adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) > 5'-adenylyl-imidodiphosphate (AMP-PNP) > alpha,beta-methylene adenosine 5' triphosphate (alpha,beta-MeATP) in both sites revealed by the Ki values of 0.017 nM, 0.030 nM, 0.058 nM and 0.147 nM respectively for the high affinity binding site and values of 0.57 microM, 0.87 microM, 2.20 microM and 4.28 microM respectively for the second binding site. 3. Studies of the P2-purinoceptors present in synaptosomes were also performed with [35S]-ADP-beta-S. This radioligand showed two binding sites the first with Kd and Bmax values of 0.11 +/ 0.022 nM and 3.9 +/- 2.1 fmol mg-1 of protein respectively for the high affinity binding site obtained from the Scatchard plot. The second binding site showed a Ki of 0.018 +/- 0.0035 microM obtained from displacement curves. 4. Competition studies with diadenosine polyphosphates of [35S]-ADP-beta-S binding showed a displacement order of Ap4A > Ap5A > Ap6A in the high affinity binding site and Ki values of 0.023 nM, 0.081 nM and 5.72 nM respectively. The second binding site potency order was Ap5A> Ap4A > Ap6A,with Ki values of 0.28 microM, 0.53 microM and 5.32 microM respectively.5. Displacement studies of [35S]-ADP-beta-S with P2 purinoceptor agonists showed the following potency pattern: ADP-beta-S > AMP-PNP >alpha,beta-MeATP with Ki values of 0.021 nM, 0.029 nM 0.215 nM respectively in the high affinity binding site. 2-Methylthio-adenosine 5'-triphosphate (2MeSATP) was unable to displace [35S]-ADP-beta-S in this binding site. The second binding site showed a profile of ADP-beta-S> a,beta-MeATP> AMP-PNP > 2MeSATP and Ki values of 0.0 18 microM, 0.212 microM, 0.481 microM and 18.04 microM respectively.6. These studies suggest the presence of a new P2-purinoceptor in rat brain synaptosomes with high affinity for diadenosine polyphosphates which we tentatively designate as P2d. PMID- 8485621 TI - Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: milacemide. AB - 1. The kinetics and metabolism of milacemide have been studied in an animal model which allows the simultaneous investigation of the temporal inter-relationships of drugs and metabolites in blood (pharmacokinetics) and cerebrospinal fluid (CSF, neuropharmacokinetics) in individual freely moving rats. 2. Milacemide dose dependently increased CSF glycine and glycinamide (intermediary metabolite) concentrations. This confirms that milacemide is a CNS glycine prodrug. 3. Pretreatment with L-deprenyl (2 mg kg-1), a specific inhibitor of monoamine oxidase type B (MAO-B), almost completely prevented the formation of glycinamide and increased milacemide accumulation in CSF. Tmax and t1/2 were significantly increased and Cmax and AUC values were decreased for glycinamide compared to controls. Pretreatment with clorgyline (5 mg kg-1), a specific inhibitor of MAO type A, only moderately decreased glycinamide Cmax and AUC values. 4. After milacemide administration (100, 200 and 400 mg kg-1, i.p.) serum and CSF milacemide concentrations rose linearly and dose-dependently. Serum glycinamide concentrations exhibited small dose-dependent rises but these were not linearly related. In contrast, CSF glycinamide concentrations rose linearly and dose dependently with Cmax values 2.5, 3.2 and 4.1 times greater than the corresponding values for serum glycinamide after giving 100, 200 and 400 mg kg-1 respectively of milacemide. 5. Serum glycine concentrations were unaffected but CSF concentrations increased dose-dependently and these were significant at the higher milacemide doses (200 and 400 mg kg-1). Animals given 400 mg kg-1 milacemide had glycine values which were still significantly elevated 7 h later. 6. In conclusion, serum milacemide rapidly enters and equilibrates with the CNS compartment where it is metabolised primarily by MAO-B to glycinamide and finally to glycine. Metabolism in the peripheral compartment is negligible. PMID- 8485622 TI - Differential changes of adrenoceptor- and muscarinic receptor-linked prostacyclin synthesis by the aorta and urinary bladder of the diabetic rat. AB - 1. The effect of experimental diabetes mellitus (DM; hyperglycaemic, non ketototic; 2 months duration) in the rat on receptor-linked prostacyclin (PGI2) synthesis (measured as 6-oxo-PGF1 alpha by radioimmunoassay) was studied in the aorta and urinary bladder using adrenaline, angiotensin II (AII) and acetylcholine (ACh). Signal transduction systems were studied via stimulation of PGI2 synthesis with phorbol ester dibutyrate (PDBU; a protein kinase C activator [PKC]), Ca2+ ionophore A23187 (A23187) and thapsigargin (both elevate intracellular Ca2+, activating phospholipase A2 [PLA2]) and arachidonate (AA; substrate for PGI2 synthesis). 2. In response to adrenaline, AII and phorbol ester, aortic PGI2 release was markedly reduced (all > 75%) in diabetic rats compared to controls. EC50s of the dose-response curves for adrenaline, AII and PDBU were also markedly increased in aortae from DM rats compared to controls. Although there was decreased output of PGI2 in response to A23187 by aortae from diabetic rats compared to controls, there was no difference in the EC50s (mean +/ s.e. mean: diabetic, 2.7 +/- 0.2 x 10(-6) M; controls 2 +/- 0.18 x 10(-6) M). There were no differences in PGI2 release (or in the EC50s) in response to thapsigargin or AA between aortae from diabetic and control rats. 3. In the urinary bladder, there was a marked increase in PGI2 output in response to ACh and a marked decrease in EC50s for the ACh-PGI2 dose-response curves in diabetic rats (EC50 = 5.8 +/- 0.32 x 10(-7) M) compared to controls (EC50 = 2.2 +/- 0.15 x 10(-6) M). Although there was an increase in PGI2 output in the urinary bladders from diabetic rats in response to A23187, there were no differences in the EC50s (control, 1.8 +/- 0.2 x 10-6 M; diabetic, 1.1 +/- 0.15 X 10-6 M). In the urinary bladders, there were no differences in PGI2 output (or the EC50s) in response to PDBU, thapsigargin or AA between diabetic or control rats.4. These data indicate that: (i) reduced PGI2 synthesis coupled to adrenoceptors and AII receptors in the aortae of diabetic rats may be due to diminished PKC activity and not to changes in receptor density and/or affinity, Ca2+ stores, PLA2, cyclo-oxygenase or PGI2 synthase; (ii) the diametrically opposite effect of DM on ACh-stimulated PGI2 synthesis is not due to an increase in PKC activity, but possibly to an increase in muscarine receptor number and/or affinity; (iii) changes in receptor linked PGI2 synthesis are not ubiquitous in experimental DM and may be organ specific. PMID- 8485623 TI - Inhibition of spinal opioid antinociception by intrathecal beta-endorphin1-27 in the rat. AB - 1. The effects of intrathecal (i.t.) administration of beta-endorphin and two shorter fragments, human and ovine beta-endorphin1-27, were examined for antinociceptive activity in the tail-flick and paw-pressure tests in the rat. Additionally, the ability of ovine beta-endorphin1-27 to influence the action of i.t. beta-endorphin, morphine and [D-Pen2-D-Pen5]enkephalin (DPDPE) was also examined in these tests. 2. After i.t. injection, beta-endorphin produced potent dose-related antinociception in the tail-flick and paw-pressure tests. Shorter endorphins produced much weaker effects. The order of antinociceptive efficacy was beta-endorphin > human beta-endorphin1-27 > ovine beta-endorphin1-27. 3. Administration of ovine beta-endorphin1-27 (0.72, 1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of beta-endorphin (2.88 nmol, i.t.) in the tail-flick and paw-pressure tests. 4. Both i.t. morphine and DPDPE produced dose related antinociception in the tail-flick and paw-pressure tests. The potency of DPDPE was lower than that of morphine in both tests; however, the effect of DPDPE was weaker in the paw-pressure test. 5. Administration of ovine beta-endorphin1 27 (1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of morphine (14.9 nmol, i.t.) in both tests and the effect of DPDPE (38.7 nmol) in the tail-flick test. 6. The results show that beta-endorphin1-27 acts as an opioid antagonist at the spinal level in the rat. Its ability to inhibit the action of morphine and DPDPE suggests that it may attenuate beta-endorphin action by an interaction with mu- and/or delta-opioid receptors. PMID- 8485624 TI - Pharmacological characterization of the contractile responses to angiotensin analogues in guinea-pig isolated longitudinal muscle of small intestine. AB - 1. The contractile responses to angiotensin II, angiotensin III and two synthetic analogues, [Lys2]angiotensin II and [Sar1]angiotensin II, in the guinea-pig isolated longitudinal muscle preparation of small intestine have been characterized in vitro. 2. Tachyphylaxis to the angiotensin analogues was reduced by use of a Krebs-Henseleit solution containing a raised (sub-contractile) concentration of potassium (11.2 mM). Under these conditions. reproducible cumulative concentration-response curves to all agonists were established. The pD2 estimates for angiotensin II, [Lys2]angiotensin II, angiotensin III and [Sar1]angiotensin II were 9.15 +/- 0.14, 7.42 +/- 0.06, 7.69 +/- 0.18 and 9.50 +/ 0.15 respectively and the maximum responses achieved were not significantly different. 3. The contractile responses to angiotensin II, angiotensin III and [Sar1]angiotensin II were reduced by greater than 80% by tetrodotoxin (TTX; 0.1 microM). However, the responses to [Lys2]angiotensin II were reduced by only 63 +/- 5%. Atropine (0.1 microM) also reduced the responses to angiotensin II, angiotensin III and [Lys2]angiotensin II, although its effect was less than that produced by TTX. Furthermore, while responses to these agonists were not significantly modified by the NK1 receptor antagonist (+/-)-CP-96,345 (30 nM) alone, the combined pre-incubation with both atropine and (+/-)-CP-96,345 reduced maximum agonist responses to a level not significantly different from those produced by TTX. 4. Indirect and direct contractile responses to angiotensin II and [Lys2]angiotensin II (in the presence of TTX) respectively were characterized by use of the selective AT1 receptor antagonist, losartan and the AT2 receptor antagonist, PD123177. Losartan produced parallel rightward displacement of the concentration-response curve to angiotensin II and [Lys2]angiotensin II, with an estimated pKB of 8.56(8.42-8.68) and 9.18 (8.63-9.50) respectively. The AT2 receptor antagonist, PD123177 (3 microM) failed to modify the contractile responses to either angiotensin II or [Lys2]angiotensin II.5. We conclude that two populations of angiotensin II receptors exist in the guinea-pig longitudinal muscle of small intestine, one located neuronally mediating the release of both acetylcholine and substance P and the other located on the smooth muscle mediating direct contractile responses. The neuronal component provides the major contribution to the agonist responses. Both receptor populations are of the AT1 receptor subtype. PMID- 8485625 TI - The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents. AB - 1. The effects of the glycine/N-methyl-D-aspartate (NMDA) receptor antagonist, R (+)-HA-966 on the neurochemical and behavioural responses to phencyclidine (PCP) and dizocilpine (MK-801) have been determined in rodents. 2. In rats, pretreatment with PCP (5 and 10 mg kg-1) or MK-801 (0.25 and 0.5 mg kg-1) dose dependently stimulated dopamine turnover in nucleus accumbens, amygdala and medial prefrontal cortex, but had no effect in striatum. In contrast, pretreatment with (+)-HA-966 (10 and 30 mg kg-1) did not affect dopamine turnover in any brain region investigated. 3. Pretreatment with (+)-HA-966 (10 and 30 mg kg-1) significantly antagonized the stimulation of dopamine turnover induced by both PCP (10 mg kg-1) and MK-801 (0.5 mg kg-1) in rat nucleus accumbens, amygdala and medial prefrontal cortex. 4. Intracerebral dialysis studies in conscious rats demonstrated that systemic injection of PCP (10 mg kg-1) markedly stimulated dopamine release from the nucleus accumbens, an effect that was abolished by pretreatment with (+)-HA-966 (30 mg kg-1). 5. Pretreatment with PCP (3-30 mg kg 1) or MK-801 (0.1-1.6 mg kg-1) significantly increased locomotor activity in mice. In contrast, subcutaneous injection of (+)-HA-966 (10-100 mg kg-1) failed to stimulate activity. 6. Pretreatment with (+)-HA-966 (10 and 30 mg kg-1) dose dependently antagonized both PCP (10 mg kg-1) and MK-801 (0.4 mg kg-1) induced hyperactivity in mice. 7. Blockade of PCP-induced hyperactivity by (+)-HA-966 is unlikely to be explained by the induction or potentiation of sedation/ataxia since PCP-induced rotarod deficits were not significantly different in mice pretreated with (+)-HA-966 (30 mg kg-1) or saline.8. The results demonstrate that (+ )-HA-966 antagonizes both the neurochemical and behavioural effects of PCP and MK-801, possibly through interactions at the glycine/NMDA receptor. PMID- 8485626 TI - Analysis of the CCKB receptor antagonism of virginiamycin in guinea-pig ileum longitudinal myenteric plexus. AB - 1. Virginiamycin, a macrolide reported to bind selectively to CCKB/gastrin receptors has been studied in a functional test, namely cholecystokinin-induced contraction of guinea-pig ileum myenteric plexus (LMMP). 2. Virginiamycin (1-10 microM) antagonized the selective CCKB agonist cholecystokinin tetrapeptide (CCK 4). The antagonism appeared not to be competitive as the highest concentration (10 microM) caused a reduction of its maximal effect. An apparent pA2 of 6.64 +/- 0.06 (s.e.) could be estimated if this depression was ignored. The selective CCKB antagonist, L-365,260 (0.01-0.3 microM) antagonized competitively the CCK-4 induced contraction and a pKB of 8.60 +/- 0.16 (s.e.) was estimated. 3. The combined dose-ratio analysis for virginiamycin, tested at 3 and 10 microM in association with 0.03 and 0.1 microM L-365,260, respectively, resulted in observed log dose-ratios of 1.39 and 1.53. That was consistent with both antagonists acting on the same receptor in LMMP. 4. These data, represent the first evidence of the antagonism of virginiamycin in a functional assay and they support the hypothesis of homogeneity between CCKB receptors in the CNS and in peripheral tissues. PMID- 8485627 TI - Inhibition by N omega-nitro-L-arginine methyl ester of the electrocortical arousal response in rats. AB - In rats chronically implanted with cannulae into one lateral cerebral ventricle and recording electrodes onto the fronto-parietal cortex, the effects of systemic or intraventricular administration of the nitric oxide (NO) synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), on electrocortical (ECoG) arousal response evoked by sound stimulation were studied. In control animals, a single acoustic stimulation (80 dB for 15 s) produced a significant decrease in ECoG total voltage power lasting approximately 25 s. No tolerance developed after repeating the same sound stimulation at 15, 30, 60 min and 24 h intervals. Under these experimental conditions, pretreatment with L-NAME, given systemically (10 mg kg-1, i.p.) or intracerebroventricularly (300 micrograms), significantly reduced the sound-evoked arousal response 1 h and 15 min later, respectively. In conclusion, the present data are in favour of a physiological role of NO in the control of arousal mechanisms. PMID- 8485628 TI - Fendiline inhibits L-type calcium channels in guinea-pig ventricular myocytes: a whole-cell patch-clamp study. AB - 1. Fendiline, a diphenylalkylamine type of antianginal drug, was examined for its effects on L-type calcium channels in guinea-pig ventricular myocytes by the whole-cell patch-clamp technique. 2. Fendiline (0.3-100 microM) applied extracellularly inhibited the calcium channel current (ICa) in a concentration- and time-dependent manner. The IC50 of fendiline was 17.0 +/- 2.43 microM and the Hill slope was 1.39 +/- 0.23. 3. Inhibition of ICa by fendiline appeared with an onset of less than 3 s. 4. Fendiline inhibited ICa at all the membrane potentials tested and shifted the current-voltage curve upwards. The overall calcium channel conductance (gCa) of the cell was reduced and conductance-voltage curve was shifted to the left in the presence of fendiline. 5. Isoprenaline (0.5-1 microM), a beta-adrenoceptor agonist, partially reversed the inhibitory effect of fendiline on ICa. 6. It is suggested that fendiline applied extracellularly blocks L-type calcium channels and reduces calcium channel conductance of the cell. The calcium channels thus inhibited are, nevertheless, still available for beta-adrenoceptor stimulation. PMID- 8485629 TI - Redirection of arachidonic acid metabolism by ICI D1542: effects on thrombus formation in the coronary artery of the anaesthetized dog. AB - 1. The effects of simultaneous redirection of arachidonic acid metabolism, by inhibition of thromboxane A2 (TXA2) synthase and blockade of the platelet thromboxane A2 receptor (TP-receptor), was examined on the rate of thrombus formation in a stenosed coronary artery with damaged endothelium in an anaesthetized dog. 2. Redirection of arachidonic acid metabolism was achieved by intravenous doses of ICI D1542, a selective and potent inhibitor of TXA2 synthase and the TP-receptor. 3. Redirection of arachidonic acid metabolism was demonstrated in whole blood, stimulated ex vivo by collagen. The ED50 for inhibition of TXB2 production was 7.1 micrograms kg-1, i.v.; there were corresponding increases in the production of the eicosanoids prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. 4. Thrombus formation was inhibited by D1542 (ED50 0.55 micrograms kg-1, i.v.), but could be restarted by an intravenous infusion of adrenaline (0.2-38 micrograms kg-1 min-1, i.v.). In the presence of the maximum effective dose of D1542 (1 mg kg-1, i.v.) a 190 fold increase in the infusion rate of adrenaline was required to restore thrombus formation. 5. In the presence of D1542, removal of endoperoxide metabolites by inhibition of cyclo-oxygenase with aspirin (5 mg kg-1, i.v.) caused thrombus formation to restart, indicating the ability of the endoperoxide metabolites to inhibit thrombus formation in vivo. 6. These results indicate that, in the stenosed and damaged coronary artery of the dog, redirection of arachidonic acid metabolism by D1542 is more effective at preventing thrombus formation than inhibition of cyclo-oxygenase by aspirin. PMID- 8485630 TI - Degradation of acetylcholine in human airways: role of butyrylcholinesterase. AB - 1. Neostigmine and BW284C51 induced concentration-dependent contractions in human isolated bronchial preparations whereas tetraisopropylpyrophosphoramide (iso OMPA) was inactive on airway resting tone. 2. Neostigmine (0.1 microM) or iso OMPA (100 microM) increased acetylcholine sensitivity in human isolated bronchial preparations but did not alter methacholine or carbachol concentration-effect curves. 3. In the presence of iso-OMPA (10 microM) the bronchial rings were more sensitive to neostigmine. The pD2 values were, control: 6.05 +/- 0.15 and treated: 6.91 +/- 0.14. 4. Neostigmine or iso-OMPA retarded the degradation of acetylcholine when this substrate was exogenously added to human isolated airways. A marked reduction of acetylcholine degradation was observed in the presence of both inhibitors. Exogenous butyrylcholine degradation was prevented by iso-OMPA (10 microM) but not by neostigmine (0.1 microM). 5. These results suggest the presence of butyrylcholinesterase activity in human bronchial muscle and this enzyme may co-regulate the degradation of acetylcholine in this tissue. PMID- 8485631 TI - Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine-xanthine oxidase free radical generating system. AB - 1. Endothelial barrier function was assessed by use of an in vitro model in which transfer of trypan blue-labelled albumin was measured across monolayers of bovine aortic endothelial cells grown on polycarbonate membranes. 2. Addition of either hypoxanthine (0.2 mM) or xanthine oxidase (20 mu ml-1) alone during a 90 min incubation did not affect albumin transfer across endothelial cell monolayers, but a combination of both increased transfer. 3. The increase in albumin transfer induced by hypoxanthine and xanthine oxidase was abolished by catalase (3 u ml 1), reduced by allopurinol (4 mM), but unaffected by superoxide dismutase (6000 u ml-1), the hydroxyl radical scavengers, mannitol (15 mM), dimethylthiourea (10 mM) and N-(2-mercaptopropionyl)-glycine (1 mM), the iron chelator, deferoxamine (0.5 mM), ferric chloride (50 microM), an inhibitor of nitric oxide synthase, NG nitro-L-arginine (30 microM), or the antioxidant, dithiothreitol (3 mM). 4. Hydrogen peroxide (0.1-30 mM) itself increased albumin transfer across endothelial cell monolayers, exhibiting a biphasic concentration-response curve. The increase induced by 0.1 mM hydrogen peroxide was abolished in the presence of 0.3 u ml-1 catalase whilst that induced by 10 mM hydrogen peroxide was abolished by 3000 u ml-1 catalase. 5. Homocysteine (0.5-1.5 mM) did not affect albumin transfer across endothelial monolayers when added alone, but when added in combination with copper sulphate (50 microM), which catalyses its oxidation, a significant increase in albumin transfer was observed. 6. The increase in albumin transfer induced by the combination of homocysteine (1.5 mM) and copper sulphate was abolished by catalase (1 u ml-1), but was unaffected by superoxide dismutase (6000 u ml-1), mannitol (15 mM), dimethylthiourea (1 mM) or deferoxamine (0.5 mM).7. The data suggest that the endothelial barrier dysfunction induced by the combination of hypoxanthine and xanthine oxidase is mediated solely by the action of hydrogen peroxide and not by superoxide anion, hydroxyl radical, peroxynitrite anion or hypochlorous acid. The copper-catalysed oxidation of homocysteine also induces endothelial barrier dysfunction through the generation of hydrogen peroxide.These findings may have relevance to the endothelial barrier dysfunction associated with ischaemia reperfusion injury and the atherogenic actions of homocysteine. PMID- 8485632 TI - The effects of N omega-nitro-L-arginine methyl ester, sodium nitroprusside and noradrenaline on venous return in the anaesthetized cat. AB - 1. The vascular actions of N omega-nitro-L-arginine methyl ester (L-NAME), sodium nitroprusside and noradrenaline were investigated in cats under chloralose anaesthesia with controlled vascular tone and ventilation. Cardiac output, heart rate, vascular pressures and mean circulatory filling pressure (MCFP) were measured. Total peripheral resistance (TPR) and resistance to venous return (Rvr) were calculated from steady-state readings. 2. L-NAME (37 mumol kg-1, i.v.) administered to ten cats receiving noradrenaline (6 nmol kg-1 min-1, i.v.) increased aortic pressure by 47.5 +/- 7.1 mmHg from 106 mmHg, and MCFP by 1.56 +/ 0.36 mmHg from 10.0 mmHg (means +/- s.e. means). Mean changes in portal venous pressure, RAP and heart rate were not significant. Cardiac output fell by 29.7 +/ 3.3% from 130 ml min-1 kg-1. TPR rose by 108 +/- 7.2% from 796 mmHg l-1 min kg and Rvr by 58.4 +/- 4.5% from 64 mmHg l-1 min kg. 3. Infusion of sodium nitroprusside into cats receiving noradrenaline evoked dose-related falls in aortic pressure, MCFP, TPR and Rvr. Changes in portal venous pressure, RAP and heart rate were not significant and cardiac output fell slightly. After L-NAME, sensitivity to nitroprusside was increased by 139 +/- 34% for MCFP, 176 +/- 19% for TPR and 351 +/- 39% for Rvr, and cardiac output rose slightly. The nitroprusside infusion required to restore TPR after L-NAME was estimated to be 5.8 x 10(+/- 0.41) nmol kg-1 min-1, which was approximately three times more than that required to restore MCFP. 4. Infusion of noradrenaline evoked dose-related increases in aortic and portal venous pressures, heart rate, cardiac output, MCFP, TPR and Rvr. After L-NAME and nitroprusside (4.4 nmol kg-1 min-1, i.v.),TPR and Rvr were not significantly different, but MCFP was reduced by 1.76 +/- 0.24 mmHg, and cardiac output by 22 +/- 1.9%. After subsequent expansion of the circulating blood volume (5-7.5 ml kg-1 dextran-saline), mean values for all parameters were restored to their previous levels. Sensitivity to noradrenaline was not significantly altered for heart rate, TPR and Rvr but was reduced by 31.8 +/- 12%for MCFP and by 66.5 +/- 18% for cardiac output.5. The depression of cardiac output by L-NAME is attributed to the increase in Rvr, partly compensated by the rise in MCFP. For a given rise in MCFP, the increase in R, was seven times greater after L-NAME than after noradrenaline, and the difference in the relative actions of the two drugs on resistance and capacitance vessels largely accounts for their contrasting effects on venous return. A procedure is suggested for replacement of vascular nitric oxide by nitroprusside infusion and blood volume expansion. PMID- 8485633 TI - Relaxing actions of corticotropin-releasing factor on rat resistance arteries. AB - 1. Although it well established that corticotropin-releasing factor (CRF) injected i.v. can cause hypotension and vasodilatation, there is no in vitro evidence that CRF acts as a vasodilator. We have therefore tested the hypothesis that the hypotensive effect of i.v. CRF is due to a direct vasodilator action by carrying out experiments in vitro on rat resistance arteries (i.d. 150-300 microns). 2. Initial in vivo experiments confirmed that CRF (1.5 nmol.kg-1) injected i.v. caused hypotension in rats, this being partially antagonized by the CRF analogue CRF9-41. 3. For the in vitro experiments, vessels were taken from the mesenteric, cerebral and femoral vascular beds, and mounted as ring preparations in an isometric myograph. The vessels were pre-contracted with one of 3 agonists (prostaglandin F2 alpha, arginine vasopressin or noradrenaline) or with a high-potassium solution (K+). 4. With maximal concentrations of the agonists, CRF caused relaxation of mesenteric and cerebral vessels with 10 nM, and near complete relaxation with 100 nM. Femoral vessels pre-constricted with agonists and all vessels pre-constricted with K+ were less affected by CRF. In the mesenteric vessels, with sub-maximal levels of pre-constriction, CRF caused substantial relaxation at 1 nM and could cause complete relaxation at 10 nM. 5. The relaxant effect of CRF on contractions of mesenteric vessels was antagonized by 100 nM CRF9-41. Neither tetraethyl ammonium (30 mM) nor glibenclamide (3 microM) antagonized the relaxant effect of CRF. 6. The relaxant effect of CRF on mesenteric small arteries was found to be unaffected by removal of the endothelium. 7. The results indicate that CRF causes an endothelial-independent vasodilatation of rat resistance arteries under in vitro conditions at concentrations which are consistent with this being an important cause of the hypotension observed with i.v. injection of CRF. PMID- 8485634 TI - Effects of high calcium diet on arterial smooth muscle function and electrolyte balance in mineralocorticoid-salt hypertensive rats. AB - 1. The effects of a high calcium diet (2.5%) on blood pressure, electrolyte balance, plasma and tissue atrial natriuretic peptide (ANP), cytosolic free Ca2+ concentration ([Ca2+]i), and arterial smooth muscle responses were studied in one kidney deoxycorticosterone (DOC)-NaCl hypertensive Wistar rats. 2. Calcium supplementation for 8 weeks markedly attenuated the development of DOC-NaCl hypertension and the associated cardiac hypertrophy, and prevented the DOC-NaCl induced sodium-volume retention as judged by reduced plasma Na+, and decreased plasma and ventricular ANP concentrations in high calcium-fed DOC-NaCl rats. However, calcium supplementation did not affect the DOC-NaCl-induced rise in platelet [Ca2+]i. 3. Smooth muscle contractions of isolated mesenteric arterial rings in response to depolarization by K+ (20-30 mM) were enhanced in DOC-NaCl treated rats, this enhancement being abolished by concurrent oral calcium loading. The Ca2+ entry blocker nifedipine (10 nM) inhibited the contractions induced by K+ (30-125 mM) more effectively in DOC-NaCl rats than in controls, while the inhibition in calcium-loaded DOC-NaCl rats was significantly greater than in controls only with 30 mM K+. 4. The contractions of mesenteric arterial rings induced by omission of K+ from the organ baths were used to evaluate cell membrane permeability to ions. In chemically denervated rings the onset of the gradual rise in contractile force in K(+)-free medium occurred earlier, and the rate of the contraction was faster in DOC-NaCl-treated rats than in controls and high calcium-fed DOC-NaCl rats. Smooth muscle relaxation induced by 0.5 mM K+ upon K(+)-free contractions was clearly slower in DOC-NaCl rats than in controls and calcium-supplemented DOC-NaCl rats. 5. The functions of arterial smooth muscle Na+, Ca2+ exchange and Ca(2+)-ATPase were evaluated by the aortic contractions elicited by low Na+ medium, and the subsequent relaxation responses induced by Ca(2+)-free solution (in the presence of 5 mM caffeine, 1 microM nifedipine and 10 microM phentolamine). The rate of aortic low Na+ contractions (evaluating Ca2+ influx via Na+, Ca2+ exchange), as well as that of subsequent relaxations was slower in DOC-NaCl-treated rats than in controls, whether the relaxation was induced in normal (144.0 mM) or low (1.2 mM) organ bath Na+ concentration (reflecting Ca2+ extrusion by both Ca(2+)-ATPase and Na+, Ca2+ exchange, and by Ca(2+)-ATPase alone, respectively). However, in calcium supplemented DOC-NaCl rats the aortic responses did not differ from control. The difference between the relaxation rate in normal and low Na+ concentration in each aortic ring,representing the contribution of Na+, Ca2+ exchange in these relaxations, was comparable in all groups.6. In conclusion, calcium supplementation clearly attenuated the development of hypertension, cardiac hypertrophy, and sodium retention induced by the DOC-NaCI treatment. However, the associated rise in platelet [Ca2+], was not prevented, suggesting that in this form of experimental hypertension increased dietary calcium does not lower blood pressure by reducing [Ca2+]i. The results from vascular responses in vitro suggest that in arterial smooth muscle the DOC-NaCl treatment increased contractile sensitivity to depolarization, voltage-dependent Ca2+ entry and cell membrane permeability to ions, and attenuated relaxation responses and vascular Na+, K+-ATPase function. The results further suggest reduced ability of the cell membrane to transport Ca2+ (possibly via Ca2+-ATPase) in DOC-NaCl hypertension. The high calcium diet opposed these alterations. The present results thus provide evidence that the antihypertensive effect of a high calcium diet in mineralocorticoid-salt hypertension is mediated by its beneficial effects on systemic sodium balance and arterial smooth muscle function. PMID- 8485635 TI - Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation. AB - 1. Cholecystokinin (CCK) has been shown to diminish opioid analgesia. Here we investigate whether changes in the physiological levels of spinal CCK are responsible for the enhanced potency of spinal morphine in animals following carrageenin inflammation, as compared with normal animals. 2. Single dorsal horn nociceptive neurones were recorded in intact halothane-anaesthetized rats in the presence and absence of carrageenin-induced inflammation and comparisons were made between the two groups of animals. Inflammation was induced by the injection of 100 microliters of 2% lambda-carrageenin into the hind paw. 3. The inhibitory effect of intrathecal morphine on the C-fibre-evoked responses of the neurones was enhanced in the carrageenin-treated animals such that the effects of 0.25 microgram and 10 micrograms of morphine in normal animals were comparable to those of 0.01 microgram and 2.5 micrograms in the carrageenin animals. The effect of 0.2 mg kg-1 of the CCKB antagonist, L-365,260, on the antinociceptive potency of intrathecal morphine was examined in both groups of animals. In normal animals, L-365,260 produced a significant enhancement in the effect of morphine indicating a tonic CCK modulation in these animals, but it had no effect on the inhibitions produced by either dose of morphine in the carrageenin animals. 4. The inhibition of the C-fibre-evoked response produced by intrathecal morphine in the presence of 1 microgram of CCK was examined in both groups of animals. CCK attenuated the effects of morphine only in animals with carrageenin inflammation, having no effect on the action of morphine in normal animals. 5. The effects of both CCK and L-365,260 were therefore dependent on the inflammatory state of the animal, with each drug being active in opposite situations.6. We propose that in normal animals, morphine may produce a maximal stimulation of the release of CCK such that exogenous CCK is unable to reduce further the analgesic effects under these conditions.However, the differential effects of the agonist and antagonist in the normal and inflamed rats points to a role of CCK in the enhanced opiate actions. This enhancement of the potency of spinal morphine in inflammation is best explained by a reduction in spinal CCK release by morphine in this state. PMID- 8485636 TI - Quinapril treatment and arterial smooth muscle responses in spontaneously hypertensive rats. AB - 1 The effects of long-term angiotensin-converting enzyme inhibition with quinapril on arterial function were studied in spontaneously hypertensive rats, Wistar-Kyoto rats serving as normotensive controls. 2 Adult hypertensive animals were treated with quinapril (10 mg kg-1 day-1) for 15 weeks, which reduced their blood pressure and the concentrations of atrial natriuretic peptide in plasma and ventricular tissue to a level comparable with that in normotensive rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Compared with normotensive and untreated hypertensive rats, responses to noradrenaline were attenuated in hypertensive animals on quinapril, both force of contraction and sensitivity being reduced. Quinapril also attenuated maximal contractions but not sensitivity to potassium chloride. Nifedipine less effectively inhibited vascular contractions in normotensive and quinapril-treated than in untreated hypertensive rats. 4 Arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitrite, isoprenaline) mechanisms were similar in normotensive and quinapril treated rats and more pronounced than in untreated hypertensive rats. 5 Cell membrane permeability to ions was evaluated by means of potassium-free solution induced contractions of endothelium-denuded denervated arterial rings. These responses were comparable in normotensive and quinapril-treated rats and less marked than in untreated hypertensive rats. 6 Intracellular free calcium concentrations in platelets and lymphocytes, measured by the fluorescent indicator quin-2, were similar in normotensive and quinapril-treated rats and lower than in untreated hypertensive rats. 7 In conclusion, quinapril treatment improved relaxation responses and attenuated contractions in arterial smooth muscle of hypertensive rats. These changes may be explained by diminished cytosolic free calcium concentration, reduced cell membrane permeability, and alterations in dihydropyridine-sensitive calcium channels following long-term angiotensin-converting enzyme inhibition. PMID- 8485638 TI - Anthelmintic resistance--can science win? PMID- 8485637 TI - Effects of P1060 and aprikalim on whole-cell currents in rat portal vein; inhibition by glibenclamide and phentolamine. AB - 1 Smooth muscle cells of the rat portal vein were dispersed by enzymatic treatment and recordings of whole-cell currents were made by the voltage-clamp technique. The effects of the potassium (K) channel openers, P1060 (0.3-10 microM) and aprikalim (3-30 microM) on these currents were investigated. Antagonism of these agents by glibenclamide and phentolamine was also studied. 2 When cells were clamped at -10 mV, P1060 (1 microM) and aprikalim (3 microM) each induced a slowly-developing K-current (IKCO), the noise of which gradually increased. The rate of onset of IKCO was greater for P1060 than for aprikalim. Current-voltage plots showed that P1060 and aprikalim each caused an approximately 25 mV negative shift of the reversal potential at zero current. 3 P1060 (1 microM) and aprikalim (3 microM) each inhibited the slowly activating, slowly inactivating delayed rectifier current, ITO. 4 Addition of MgATP (5 mM) to the recording pipette inhibited the generation of IKCO by P1060 (1 microM) and reduced the accompanying inhibition of ITO. 5 Stationary fluctuation analysis of the current noise associated with IKCO induced by P1060 (1 microM) or aprikalim (3 microM) at a holding potential of -10 mV indicated that the unitary conductance of the underlying K-channels was 10.5 pS at 0 mV under the quasi physiological conditions of the experiment. 6 In the absence of K-channel openers, neither phentolamine (30-100 microM) nor glibenclamide (1 microM) affected the magnitude of control non-inactivating currents. However, phentolamine (30-100 microM), but not glibenclamide (1 microM) inhibited the control delayed rectifier current ITO. 7. After induction of IKCO by P1060 (1 microM) or aprikalim (3 microM), subsequent exposure to glibenclamide(1 microM) or phentolamine (30 microM) inhibited this current. After aprikalim-induced reduction of ITO had developed, subsequent exposure to glibenclamide was able partially to reverse the inhibition of ITO whereas phentolamine was without effect. Pre-exposure to glibenclamide (1 microM) prevented both the generation of IKCO by aprikalim (3 microM) and the inhibitory effect of this agent on ITO.8. It is concluded that P1060 and aprikalim each induce the current IKCO by opening the same small conductance, ATP-sensitive K-channel (KATP), an effect which can be inhibited by glibenclamide orphentolamine. The opening of KATP by both P1060 and aprikalim probably involves competition between these agents and ATP for the ATP control site associated with the channel. Inhibition of the delayed rectifier current, ITO, by P1060 and aprikalim was glibenclamide-sensitive and may be caused by the induction of a state of run-down in the channel which underlies this current. PMID- 8485639 TI - Anthelmintic resistance--the state of play. AB - There is evidence that the incidence of anthelmintic resistance is increasing in livestock in countries throughout the world including the United Kingdom. Early detection of emerging drug resistance is important since reversion to susceptibility appears not to occur in highly selected homozygous strains. Because the current in vivo and in vitro assays, which generally determine the degree of disruption of normal physiological function of different parasite stages, are relatively insensitive, effort is being made to develop more direct genetic and biochemical diagnostic assays. Studies on the selection and genetics of resistance suggest that resistance is normally polygenic and arises from within the normal phenotypic range and that there are three phases in the selection process. An initial susceptible phase is followed by an intermediate one in which heterozygous resistant individuals are common within the population and finally homozygous resistant individuals predominate within the population. For these reasons low efficacy treatments, which enable the survival of heterozygous resistant individuals, and suppressive regimes, which only allow homozygous resistant individuals to survive, increase the rate of development of drug resistance. Strategies to delay the onset of resistance and control resistant strains usually incorporate minimal chemoprophylaxis, seek to maximize drug efficacy, and if possible include a 'slow' drug rotation and seek to limit host parasite contact by manipulation of the grazing environment. Although multi species mathematical models of anthelmintic resistance appear to offer a means of assessing the long term impact of these and other control strategies, current models are limited by a lack of detailed biological knowledge. In particular, more information on the status and numbers of alleles associated with resistance to specific drugs, their frequencies within populations of different species and the fitness of resistant and susceptible populations is required. Anthelmintic resistance provides an example of the adaptability of metazoan parasites under intensive selection and suggests that sustainable control strategies will require an integrated approach in which both chemotherapy and immunotherapy, together with environmental management are used to control nematodoses. PMID- 8485640 TI - Equine Cushing's disease. AB - In the horse, adenomata of the pairs intermedia of the pituitary gland have been associated with the distinct clinical entity of Cushing's disease which arises largely as a result of excessive secretion of adrenocorticotropin (ACTH) or other proopiomelanocortin (POMC) peptides. Pars intermedia peptide secretion is under dopaminergic control and compounds such as pergolide or bromocriptine, which are dopamine agonists, can palliate the clinical signs. A variety of endocrinological abnormalities, relevant to both pathogenesis and diagnosis, may be demonstrated in equine Cushing's disease, including hyperadrenocorticism, peripheral insulin resistance and excessive POMC-peptide secretion from the pituitary gland. Preliminary studies on carbohydrate metabolism suggest that quantification of insulin activity may be a useful prognostic index in cases of equine Cushing's disease, and that insulin therapy of secondary diabetes mellitus may be indicated in some cases. PMID- 8485641 TI - A field study of ovine listerial meningo-encephalitis with particular reference to cerebrospinal fluid analysis as an aid to diagnosis and prognosis. AB - In a field study of listerial meningo-encephalitis involving 21 sheep from six silage-fed flocks, the neurological signs included profound depression, circling, involvement of the trigeminal and facial cranial nerves and lateral recumbency with propulsive limb movements. Within the six flocks the incidence of listerial meningo-encephalitis did not exceed 1% of the adult sheep at risk. Eleven of 18 (61%) adult animals were 2 years old. Evidence of an intrathecal inflammatory response in suspected listerial meningo-encephalitis cases was indicated by an increased cerebrospinal fluid (CSF) protein concentration greater than 0.4 g/l in 18 of 21 cases (86%), increased white cell count above 0.012 x 10(9)/l in 17 cases (81%) and lymphocyte percentage below 50% in all animals. None of the CSF parameters proved to be a reliable prognostic indicator because of the range of CSF values obtained and the small number of sheep which recovered. PMID- 8485642 TI - Oestrus in the British white goat: timing of plasma luteinizing hormone surge and changes in behavioural and vaginal traits in relationship to onset of oestrus. AB - Length of oestrus and timing of the LH surge was measured in six British White does, housed with a vasectomized buck (experiment 1). The following breeding season, pulsatile LH release during the cycle was measured in eight does and the pattern of behavioural and vaginal traits in relation to onset of oestrus (time 0) determined (experiment 2). In experiment 1, the interval to first oestrus after introduction of the buck on 1st October was 10.3 +/- 3.0 days (n = 6) but in experiment 2, when the buck was put in on 1st September, first oestrus occurred after 39.3 +/- 3.4 days in 7/8 does and 7 days in 1/8 does indicating that adequate exposure to short days is needed before the buck can initiate ovarian activity. LH pulse frequency increased from 0-1 pulses/8 h to 3 pulses/8 h after luteolysis, with no change in pulse amplitude, suggesting that progesterone regulates LH pulse frequency. Mean LH values rose from basal to 102.1 +/- 7.8 ng/ml, 12 +/- 1.5 h after the onset of oestrus, which was 16.3 +/- 1.7 h in length. Does sought out the buck and displayed tail wagging, bleating and restlessness from -60 h to +36 h relative to the onset of oestrus (time 0). The incidence of these activities rose at -12 h and peaked at 0 h. Tail wagging, but not bleating or restlessness, also increased in intensity at 0 h, as did the intensity with which the doe actively sought out the buck. Vulval redness and swelling and onset of a clear thin vaginal discharge were first observed 1-2 days before oestrus, becoming maximal on day 0. It was concluded that onset of frequent tail wagging was the most useful trait for detecting onset of oestrus. PMID- 8485643 TI - The role of induced virulence factors produced by Pasteurella haemolytica in the pathogenesis of bovine pneumonic pasteurellosis: review and hypotheses. AB - In the pathogenesis of pneumonic pasteurellosis, there is an abrupt commensal to pathogen shift from a predominance of P. haemolytica serotype 2 (ST2) to serotype 1 (ST1) in the bovine upper respiratory tract (URT) microfloral population. This occurs following periods of stress associated with development of this disease. Data are reviewed from recent publications supporting the contention that surface expressed ST1-specific factor(s) could be critical in mediating URT adhesion and colonization. Such factors may promote an increase in the number of ST1 organisms deposited through infective droplets into the lungs, beyond that efficiently cleared by normal lung defences. The seeding of these organisms into the lungs may provide numerous foci of infection that eventually progress into characteristic pneumonic lesions seen in the disease. PMID- 8485644 TI - An outbreak of cameline filariasis in the Sudan. AB - Sheathed microfilariae (mean length 278 +/- 10 microns SEM; mean width 7.2 +/- 0.8 microns) were detected in the blood of 7/14 housed camels (Camelus dromedarius). Microfilaraemic camels of either sex were inappetent, lethargic, reluctant to move and exhibited weakness in the hind limbs; some remained in sternal recumbency. Cardiac disorders, orchitis and skin nodules were conspicuously absent. The microfilariae showed a biphasic pattern in the blood that peaked at 20:00 and plateaued between 04:00 and 06:00. Adult filarial worms were recovered from the mesenteric and femoral arteries. Marked clinical improvement within 1-2 weeks was seen in three camels treated at 10:00 with a single subcutaneous injection of 0.2 mg/kg of ivermectin. These camels became amicrofilaraemic 2-5 days after treatment and remained so for the length of the observation period (133 days). Treatment of two camels at the time of high microfilaraemia (06:30) resulted in adverse reaction and death. PMID- 8485645 TI - Combined modality therapy increasing local control of pancreatic cancer. AB - Twenty patients with inoperable locally advanced Stage II and III pancreatic cancer were treated with combined modality therapy. Radiotherapy consisted of split courses of 2000 cGy each and, as needed, an additional 1400 cGy, separated by 2-week intervals. Simultaneous multidrug regimen chemotherapy consisted of 5 fluorouracil, continuous infusion, 1 g/m2 days 1-5; streptozotocin, 300-500 mg/m2 days 1, 2, 3; and cisplatin, 100 mg/m2 day 3 of every 4-week radiotherapy course (RT-FSP). Primary tumors decreased more than 50% in volume in 11 of 20 patients. Computed tomography scans demonstrated apparent complete disappearance of the primary tumor in 7 patients. Only 3 patients had tumor regrowth within the radiotherapy field, all after the end of radiotherapy. Local control improved as measured by increased frequency of tumor shrinkage and decreased frequency of primary tumor growth, recognizing the limitations of a pilot study and comparisons to best historical results achieved with standard short 5 fluorouracil schedules and radiotherapy. Successful local control largely eliminates the most common cause of refractory pain and may decrease the need for some forms of early palliative surgical intervention. Tumor shrinkage sometimes downstages tumors, creating frequent investigational opportunities for either elective extirpative surgery or intraoperative radiotherapy. This pilot experience also supports testing of expanded eligibility staging criteria for combined modality treatment and testing of new drugs as part of 5-fluorouracil radiotherapy-based regimens. PMID- 8485646 TI - A phase I trial of protracted 5-fluorouracil infusion and oral calcium leucovorin. AB - This phase I study of 36 patients was performed to identify the maximal tolerated dose of oral calcium leucovorin (CLV) that could be concomitantly administered with protracted 5-fluorouracil (5-FU) infusion (greater than 30 days). Administration of CLV in very small doses (5 mg p.o. q8h) with 5-FU, 200-300 mg/m2/day, resulted in excessive toxicity requiring treatment interruption in all patients. Subsequent reduction in the dose of 5-FU to 100 mg/m2/day with simultaneous administration of CLV, 5 mg p.o. q8h, decreased the toxicity and allowed for protracted administration of the combination. In subsequent patients the dose of oral CLV was increased to 22.5 mg p.o. q8h, which resulted in treatment-limiting toxicity in the majority of patients. Toxicity consisted almost exclusively of mucositis. No myelosuppression or significant organ toxicity was observed. We conclude that even low doses of oral CLV potentiate the biological effect of infusion 5-FU. If the combination is to be given on a protracted basis, 5-FU must be administered at a much smaller dosage than has been traditionally utilized. PMID- 8485647 TI - Depletion of patients' plasma tryptophan using tryptophan side-chain oxidase columns. AB - The use of the enzyme tryptophan side-chain oxidase, isolated from Pseudomonas XA, was explored in 3 patients with refractory acute lymphocytic leukemia. Patients were given either a low-tryptophan diet or tryptophan-free hyperalimentation, prior to and during therapy. Their plasma, separated by pheresis, was continuously passed through a tryptophan depletion column containing the immobilized tryptophan side-chain oxidase. Up to 4 plasma volumes were passed through the column daily, 5 days per week for 2-3 weeks, and plasma tryptophan levels, both free and total, were measured by high-performance liquid chromatography. Pre- and postcolumn plasma samples were collected throughout the pheresis procedure. All postcolumn plasma samples had unmeasurable tryptophan levels throughout the treatment period, whereas precolumn samples were always measurable. Generally, tryptophan levels of plasma isolated from peripheral blood decreased after therapy, but rebounded by the next day. The enzyme depletion column reduces circulating plasma tryptophan levels, and its use is well tolerated by patients. However, further development of this method will require study of the effects of diet and of the duration, interval, and frequency of use of this column on therapeutic efficacy. Problems include difficulties with extended diet compliance and apparently intensive mobilization of tryptophan from body stores, which may preclude the clinical application of this enzyme depletion column. PMID- 8485648 TI - O6-methylguanine-DNA methyltransferase in human normal and malignant lung tissues. PMID- 8485649 TI - Cell cycle perturbations of platinum derivatives on two ovarian cancer cell lines. AB - Cisplatin continues to be one of the most commonly used cytotoxic agent. Problems of drug resistance and nephrotoxicity have generated interest in new platinum derivatives. In this study, we used flow cytometry to study their effects on cell kinetics and to see if the extent of cell cycle perturbations can be used to determine relative potency. The following four platinum derivatives were tested: cisplatin, carboplatin, 254S, and NK121 on two human ovarian cancer cell lines: BG1 and CAOV3. Flow cytometric analysis revealed a dynamic spectrum of cell kinetic perturbations, which included sequential S-G2 block, concomitant S-G2 block, and a dominant S block with abolition of G2 block. Platinum derivatives NK121, 254S, and CARBO induced an average of 54.5 +/- 5.6, 21.2 +/- 5.5, and 2.5 +/- 2.8% more S-G2 blocks than cisplatin, respectively. When comparing the severity of S-G2 blocks and requiring a p-value of 0.05, the order of increasing potency was: cisplatin, carboplatin, 254S, and NK121. PMID- 8485650 TI - In vitro evaluation of the novel chemotherapeutic agents U-73,975, U-77,779, and U-80,244 in gynecologic cancer cell lines. AB - U-73,975 (U-73), U-77,779 (U-77), and U-80,244 (U-80) are analogs of the potent antitumor compound CC-1065. This class of drugs act as alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study was designed to compare the potencies of U-73, U-77, and U-80 with cisplatin (DDP) or adriamycin (DXR) in 10 gynecologic cancer cell lines. The mean IC50s were: U-73, 0.173 +/- 0.115 ng/ml; U-77, 0.650 +/- 0.209 ng/ml; U-80, 3.0 +/- 3.0 ng/ml; DDP, 4.40 +/- 2.83 micrograms/ml; and DXR, 0.286 +/- 0.040 micrograms/ml. U-73 appears the most potent analog, being 10(3) to 10(4) times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 10(2) to 10(3) greater potency than DDP and DXR. All the cervical, endometrial, and ovarian cell lines were sensitive to U-73, with decreasing sensitivity to U-77, U 80, DXR, and DDP in that order. U-73 as well as the other analogs appear promising chemotherapeutic agents. PMID- 8485651 TI - Response of primary colon cancer cells in hybrid spheroids to 5-fluorouracil. AB - We have measured the clonogenic survival of cells isolated directly from colon cancer surgical specimens and treated with 5-fluorouracil (5-FU). Enzymatically disassociated cells were incorporated into hybrid spheroids, consisting predominantly of nonproliferating HeLa feeder cells. Aliquots were exposed for 1.5 hr to a range of concentrations of 5-FU. From the decrease in clonogenic survival, as deduced from the frequency of colony formers among hybrid spheroids after chemical treatment, we were able to construct survival curves in 50% of the surgical specimens tested. A striking revelation was the presence of a resistant plateau in the survival curves, reminiscent of the solid tumor response to treatment with 5-FU. This resistance was absent in monolayer cultures. Evidence is presented that this resistance is due to the absence of, or delay in, cell cycle progression of cells residing in hybrid spheroids. PMID- 8485652 TI - Analysis and distribution of etoposide in rat brain tumor model: intracarotid versus intracarotid with angiotensin II-induced hypertension. AB - The brain tissue distribution of etoposide has been investigated in 9L gliosarcoma-bearing rats with or without hypertension induced by angiotensin II (AT II). The rat brain tumor models were divided into the following two groups according to etoposide administration route: intracarotid injection (IC) group and intracarotid injection with hypertension induced by AT II (IHIC) group. Ten mg/kg of etoposide was given, and 30 min and 2, 4, 8, and 24 hr later the rats were sacrificed. The drug concentrations in the serum, tumor, and normal brain tissue were analyzed by high-pressure liquid chromatography. The etoposide concentration in the serum, tumor, and normal brain tissue peaked at 30 min in both groups. The serum concentration was similar between the two groups. The etoposide concentration in the tumor was at least 2.2 times higher in the IHIC group than in the IC group at 30 min and 2 hr. The area under drug concentration curve (AUC) in the tumor in the IHIC group was about 2.2 times higher than that in the IC group. The etoposide concentration in the normal brain on the drug injection side changed only slightly from 0.5 hr to 4 hr and was about 3 times higher in the IHIC group than in the IC group. The etoposide concentration in the contralateral normal brain was very low in both groups at 30 min and disappeared thereafter. Intracarotid injection of anticancer drugs with AT II-induced hypertension further increases the drug concentration and AUC in the tumor compared with intracarotid injection alone and can be useful in treatment of malignant brain tumors. PMID- 8485653 TI - Mechanisms by which interferon potentiates chemotherapy. AB - IFNs potentiate the activity of multiple chemotherapy drugs in vitro; improved activity has been noted with 5-FU and IFN-alpha against colon carcinoma and with IFN-alpha and DTIC against melanoma. The mechanisms whereby interferon potentiates the activity of chemotherapeutic drugs are complex, and different mechanisms may be operative with different drugs and against different tumors. Both indirect immunoaugmentative effects of interferon and direct biochemical modulation of the drugs (as documented in detail with 5-FU) may play a role; further elucidation of these mechanisms will enable us to optimally utilize the combination of interferon and antineoplastic agents. PMID- 8485654 TI - Fludarabine in the treatment of lymphoproliferative malignancies. PMID- 8485655 TI - Quality of life in cancer: definition, purpose, and method of measurement. AB - Over the past 20 years, changes within medicine and society have encouraged an expansion in conceptualizing and evaluating the goals and important outcomes of medical treatments. In evaluating the care of people with cancer and other chronic illnesses, a major part of the expansion has been the inclusion of means to assess the quality of life in addition to the quantity of life associated with various treatments. This paper presents a review of the current literature on quality-of-life assessment in oncology research and practice. The review is organized around current thinking about the definition of quality of life, the purpose of quality-of-life measurement, the method of assessment, and the competing advantages and disadvantages of disease-specific versus general health outcome measurement. Recommendations for proceeding with quality-of-life measurement in oncology are provided to encourage increased attention to the need to remain closely tied to a theoretical construct. PMID- 8485656 TI - Health technology and health reform. PMID- 8485657 TI - Retroviral vector-mediated cytokine-gene transfer into tumor cells. PMID- 8485658 TI - Withholding and/or withdrawing fluids and nutrition: an opposing view. PMID- 8485659 TI - Best papers on lymphoma. PMID- 8485660 TI - The death of Bill C-203. PMID- 8485661 TI - Success story. PMID- 8485662 TI - Applicants to medical school. PMID- 8485663 TI - The Canadian National Breast Screening Study: opportunity for a rethink. PMID- 8485664 TI - Why the GE boycott? Why indeed! PMID- 8485665 TI - Why the GE boycott? Why indeed! PMID- 8485666 TI - Childproof containers. PMID- 8485667 TI - Self-help movement. PMID- 8485668 TI - Self-help movement. PMID- 8485669 TI - Self-help movement. PMID- 8485671 TI - Hysteria, or "suffocation of the mother". PMID- 8485670 TI - TGIF. PMID- 8485672 TI - Ketorolac (Toradol): a marketing phenomenon. PMID- 8485673 TI - Ketorolac (Toradol): a new analgesic or an old NSAID? PMID- 8485674 TI - Canadian physicians and euthanasia: 3. Arguments and beliefs. PMID- 8485675 TI - International correlations between gun ownership and rates of homicide and suicide. AB - OBJECTIVE: To examine international correlations between reported rates of household gun ownership and rates of homicide and suicide with a gun. DESIGN: Survey. POPULATION: People who responded to a telephone survey conducted by the 1989 International Crime Survey in 11 European countries, Australia, Canada and the United States. RESULTS: Positive correlations were obtained between the rates of household gun ownership and the national rates of homicide and suicide as well as the proportions of homicides and suicides committed with a gun. There was no negative correlation between the rates of ownership and the rates of homicide and suicide committed by other means; this indicated that the other means were not used to "compensate" for the absence of guns in countries with a lower rate of gun ownership. CONCLUSION: Larger studies are needed to examine more closely possible confounding factors such as the national tendency toward violent solutions, and more information on the type and availability of guns will be helpful in future studies. Nevertheless, the correlations detected in this study suggest that the presence of a gun in the home increases the likelihood of homicide or suicide. PMID- 8485676 TI - Variations in surgical rates in Quebec: does access to teaching hospitals make a difference? AB - OBJECTIVE: To document the geographic variations in the rates of 10 common surgical procedures in Quebec and to examine the relation between surgical rates and level of access to teaching hospitals. DESIGN: Population-based rates standardized for age and sex were calculated from 1985-88 data from MED-ECHO (the provincial hospital discharge database) for each of the 32 community health districts (departements de sante communautaire [DSCs]) in Quebec. Variation across DSCs was analysed with the use of the ratio of the highest to the lowest rate, the coefficient of variation and the systematic component of variation. On the basis of an urbanization index designed by Statistics Canada, DSCs were classified as having a low, medium, high or very high level of access to teaching hospitals. PATIENTS: All Quebec residents except those whose DSC of residence could not be traced (accounting for no more than 1.7% of patients for any study procedure) and aboriginal people from northern Quebec. SURGICAL PROCEDURES STUDIED: Appendectomy, cesarean section, cholecystectomy, coronary artery bypass grafting (CABG), hysterectomy, inguinal hernia repair, prostatectomy, tonsillectomy with or without adenoidectomy, total hip replacement and varicose vein stripping. RESULTS: There was considerable systematic variation in the surgical rates for all 10 procedures. Cesarean section, the rates of which varied the least, still exhibited almost a twofold variation between the highest and lowest rates. The rates of tonsillectomy varied the most, by a factor of more than five. With a few exceptions there was relatively little relation between the rates of the procedures within the DSCs. The rates of appendectomy, cholecystectomy, hysterectomy and tonsillectomy tended to be lower in the DSCs containing teaching hospitals, whereas the reverse was true for CABG. For the other procedures the relation between the rates and the level of access to teaching hospitals was nonsignificant. CONCLUSIONS: The overall consistency of the observed variations with those of previous studies invites a closer look at the practice patterns and the scientific basis of the clinical decisions associated with procedures showing high variations in rates. The lack of a systematic relation between the surgical rates and the level of access to teaching hospitals challenges the belief that remote regions are underserved with respect to the procedures studied. PMID- 8485677 TI - Electronic fetal monitoring: a Canadian survey. AB - OBJECTIVES: To determine the current status of electronic fetal monitoring (EFM) in Canadian teaching and nonteaching hospitals, to review the medical and nursing standards of practice for EFM and to determine the availability of EFM educational programs. DESIGN: National survey in 1989. PARTICIPANTS: The directors of nursing at the 737 hospitals providing obstetric care were sent a questionnaire and asked to have it completed by the most appropriate staff member. The response rate was 80.5% (593/737); 44 hospitals did not have deliveries in 1988 and were excluded. The remaining hospitals varied in size from 8 to 1800 (mean 162.1) beds and had 1 to 7500 (mean 617.1) births in 1988; 18.8% were teaching hospitals. RESULTS: Of the 549 hospitals 419 (76.3%) reported having at least 1 monitor (range 1 to 30; mean 2.6); the mean number of monitors per hospital was higher in the teaching hospitals than in the nonteaching hospitals (6.2 v. 1.7). Manitoba had the lowest mean number of monitors per hospital (1.1) and Ontario the highest (3.7). In 71.8% of the hospitals with monitors almost all of the obstetric patients were monitored at some point during labour. However, 21.6% of the hospitals with monitors had no policy on EFM practice. The availability of EFM educational programs for physicians and nurses varied according to hospital size, type and region. CONCLUSIONS: Most Canadian hospitals providing obstetric services have electronic fetal monitors and use them frequently. Although substantial research has questioned the benefits of EFM, further definitive research is required. In the meantime, a national committee should be established to develop multidisciplinary guidelines for intrapartum fetal assessment. PMID- 8485678 TI - Bloodborne pathogens in the health care setting: risk for transmission. PMID- 8485679 TI - Incidence of HIV infection in donated blood has fallen considerably, MD reports. PMID- 8485680 TI - Article in Canadian physics journal put academic integrity on trial. PMID- 8485681 TI - Are children's hospitals an idea whose time has come and gone? PMID- 8485682 TI - Toronto hospital takes leadership role in providing care for inner-city residents. PMID- 8485683 TI - There is more to health care than access to a health care system, Montreal symposium told. PMID- 8485684 TI - Doctor-patient relationship put under microscope at CMA leadership conference. PMID- 8485685 TI - Museum a perfect memorial to the Lady of the Lamp. PMID- 8485686 TI - Sexual harassment a significant health care issue, Canadian Medical Association committee says. PMID- 8485687 TI - Manufacturers, plastic surgeons draw fire at US forum on breast-implant issue. PMID- 8485688 TI - Health care a major topic for Canadian public policy journal. PMID- 8485689 TI - Assessment of instruments. PMID- 8485690 TI - A comparison of four glucose monitors in a hospital medical surgical setting. AB - Four bedside glucose monitors were evaluated and compared for accuracy in correlation with concomitant laboratory glucose values. Of these four monitors- Diascan, Glucometer Q.A., Accucheck, and One Touch--two bedside glucose monitors were comparable with a correlation coefficient of 0.91 for Glucometer Q.A. and 0.90 for One Touch. These two machines were then evaluated for precision and linearity. Although the Glucometer Q.A. was more precise for all three levels of glucose, the One Touch linearity was almost perfect. Lastly, in asking nursing staff for an evaluation of One Touch and Glucometer Q.A., 15 of 16 staff members preferred One Touch. PMID- 8485691 TI - The measurement of physical activity in bone density research. AB - Physical activity is often recommended as a method to prevent or treat osteoporosis. Nevertheless, it is difficult to interpret the research findings upon which this recommendation is made because of problems measuring physical activity. Studies investigating the bone density-physical activity association were reviewed. Physical activity was measured by participation in a specific form of exercise, questionnaire and interview, mechanical devices, and physiological markers of activity. In about half of the exercise participation studies, grouping criteria were problematic for the nonexercise or control group. Many discrepancies were found in the questionnaire and interview studies. Overall, little information was reported with respect to reliability or validity of measures, thereby hampering comparisons across studies. These measurement issues can provide nurses with a new perspective for evaluating studies that report the impact of physical activity on bone mass and other health outcomes as well. PMID- 8485692 TI - In theory and practice. PMID- 8485693 TI - Implementing cooperative care on an acute care medical unit. AB - Cooperative care is an approach to nursing care, based on Orem's self-care theory, that encourages patient self-care and family involvement in care giving. Patients and care partners (family members or friends) are taught by staff working on the unit. The model has been successfully implemented on acute care units at institutions across the nation. In March 1990, under the direction of our chief nurse, cooperative care was initiated at Dorn Veterans' Hospital as a part of a research project on a busy acute care medical unit. The model had already been piloted with success on the oncology unit of the institution. The purpose of this article is to describe patient, nursing, and pharmacy involvement during the implementation of cooperative care on a 40-bed acute care unit in a veteran population. PMID- 8485694 TI - The advanced practice nurse: is the time right for a singular title? PMID- 8485695 TI - Mrs. Hammond speaks. PMID- 8485696 TI - Time documentation: a question of worth. PMID- 8485697 TI - Evaluation and time documentation for the clinical nurse specialist. AB - This article introduces a time documentation tool designed to gather and record information on the many facets of the role of the CNS. A review of the literature provides background information on types of evaluation, time documentation, and the need for qualitative as well as quantitative accountability. Because existing tools did not meet the documentation needs of the authors, they designed a system that could accommodate six domains of the CNS role and provide a means to document quantitative and qualitative activities. Three CNSs pilot tested the tool for 2 months and provided a critique of the instrument for the authors. The evaluations have been summarized, and comments for individualization and frequency of use have been noted. Suggestions for future study include the need for measuring outcomes of care and documentation methods for qualitative interventions. PMID- 8485698 TI - Consultation: more than one dimension. PMID- 8485699 TI - Defining your role in ambulatory care: clinical nurse specialist or nurse practitioner? AB - A collaborative practice was established at the University of Southern California/Kenneth Norris Jr. Cancer Hospital utilizing combined roles of the CNS and nurse practitioner. The role was created out of a specific need of the physicians of the gastrointestinal malignancy service. Increased administrative and clinical responsibilities necessitated another clinical expert to be readily available for the management of the acute care private practice patients. As a CNS for both the departments of medicine and nursing, my primary responsibilities are focused within the ambulatory care area. This paper presents the concept for this position, the professional and personal benefits, advantages and disadvantages, and recommendations for nursing practice. PMID- 8485700 TI - Clinical nurse specialist subroles: foundations for entrepreneurship. AB - Entrepreneurship is a career option for nurses seeking autonomy in their practice. The six subroles of the CNS--researcher, consultant, advanced clinician, educator, leader/manager, and collaborator--provide the framework for discussion of the functional aspects of this new option. Examples demonstrate how these subroles have been used by various nurse entrepreneurs. Implications for practice and recommendations are provided. PMID- 8485701 TI - Federal action on prescriptive authority. PMID- 8485702 TI - The role of the female doctorally prepared nurse in caring for infertile women. AB - Today, in medical and nursing literature, infertility is described as a couple problem, with interventions aimed at treating the couple. While not dismissing the fact that the conception does involve both genders, the reality of infertility treatment is that the woman, not the couple, undergoes the majority of infertility testing and treatment. The numerous physical demands made of women during infertility investigation and therapy are associated with significant emotional and informational needs. As such, all infertility practices should offer supportive counseling to their clients. Incorporation of such services into general infertility treatment will ensure that the greatest number of female infertility clients receive the information and emotional support they need. The health care professional best qualified to provide these services is the female doctorally prepared nurse. By virtue of both her gender and training, she is more likely to be capable of intervening therapeutically, woman to woman, in a sensitive and empathic manner. Furthermore, she can anticipate extending her role to include the following services: (a) provision of basic gynecological care, (b) follow-up of patients on hormone therapy, (c) coordination of patient care, (d) provision of supportive counseling, and (e) participation in research. To secure a position, the female doctorally prepared nurse needs to recognize the importance of promoting herself in the infertility marketplace. Ultimately, both the establishment and survival of her role will depend on her professional uniqueness. PMID- 8485703 TI - Interstitial pressure of subcutaneous nodules in melanoma and lymphoma patients: changes during treatment. AB - Interstitial pressure (IP) is a physiological variable that may have its greatest influence on the transport of high-molecular-weight therapeutic agents. IP in tumor nodules was measured in patients with metastatic melanoma or non-Hodgkin's lymphoma to determine the influence of this physiological variable on treatment outcome. The wick-in-needle technique was used to measure IP at time points before and after treatment with a variety of immunotherapy and chemotherapy regimens. Selected patients had IP measurements during chemotherapy or immunotherapy infusions. Ultrasound or computed tomography was used to evaluate the size of the studied lesions and their relationship to normal structures. The mean baseline IP in melanoma nodules (n = 22) and lymphoma nodules (n = 7) was 29.8 and 4.7 mm Hg, respectively (P = 0.013 for the difference between tumor types). In a subset of melanoma nodules for which IP had been measured before and after treatment, the IP increased significantly over time for nonresponding melanoma lesions from a baseline of 24.4 to 53.9 mm Hg after treatment (P = 0.005) and decreased in melanoma lesions that responded to treatment where the mean baseline and post-treatment IPs were 12.2 and 0 mm Hg, respectively (P = 0.001 for the difference in IP profiles between responding and nonresponding lesions). Six of seven lymphoma nodules responded completely to chemotherapy or radiation. The single nodule that did not respond had a baseline IP of 1 mm Hg that increased to 30 mm Hg after treatment. Tumor IP differs significantly between melanoma and non-Hodgkin's lymphoma. The changes in IP over time differ significantly between responding and nonresponding melanoma lesions. IP that increases during treatment appears to be associated with tumor progression in these tumor types. PMID- 8485704 TI - Elevated levels of M(r) 92,000 type IV collagenase in human brain tumors. AB - Local invasive growth is one of the key features of primary malignant brain tumors accompanied by remodeling of the vasculature and destruction of normal brain tissue. Tissue invasiveness is an essential biological function used by a tumor to overcome the various barriers to its progression. The expression of metalloproteases has been shown to play a critical role in the invasive process in a number of tumors; however, their expression in human brain tumors has not been previously reported. In this study we showed metalloprotease activities at M(r) 240,000, 123,000, 92,000, 72,000, and 67,000 in brain tumor extracts. These enzyme activities were inhibited by EDTA, an inhibitor of metalloproteases. Significant increases in levels of protease bands at M(r) 92,000, 123,000, and 240,000 were observed in glioblastoma and metastatic lung tumors. Enzymatic inhibition and Western blotting with M(r) 92,000 type IV collagenase antibody confirmed the presence of M(r) 92,000 type IV collagenase in all samples. Quantitative analysis by densitometry showed 8-10-fold and 6-8-fold increases in M(r) 92,000 type IV collagenase activity in glioblastoma and metastatic lung carcinoma samples, respectively, when compared with normal brain, meningioma, astrocytoma, metastatic colon, and breast carcinoma samples. These findings provide evidence for elevated levels of metalloproteases in glioblastomas and suggest a therapeutic target for minimizing the invasive propensity of gliomas using protease inhibitors. PMID- 8485706 TI - 1 alpha,25-Dihydroxyvitamin D3 enhances 12-O-tetradecanoylphorbol-13-acetate- induced tumorigenic transformation and osteopontin expression in mouse JB6 epidermal cells. AB - To study the role of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in tumor promotion, we used JB6 C141.5a cells, a mouse epidermal cell model of tumor promotion. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) irreversibly induces anchorage-independent growth and tumorigenicity in these cells. Since we previously showed that calcitriol does not transform these cells but inhibits their proliferation, we hypothesized that calcitriol would inhibit TPA-induced transformation. Concurrent treatment of JB6 C141.5a cells with TPA and calcitriol revealed that calcitriol enhanced (1.7- to 10-fold, depending on dose) TPA-induced anchorage-independent growth without enhancing cell proliferation. Furthermore, a more than additive effect on osteopontin mRNA and protein levels was observed with concurrent drug treatment, which yielded a more highly phosphorylated form of osteopontin. These studies suggest coordinate regulation between the signaling pathways for calcitriol and TPA in JB6 C141.5a cells and further implicate expression of phosphorylated osteopontin in tumorigenesis. PMID- 8485705 TI - Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. AB - We have investigated the effect of chemotherapeutic and DNA damaging agents on binding of the tumor suppressor phosphoprotein p53 to its consensus DNA sequence. Activation of p53-DNA binding was seen for treatment with radiation, hydrogen peroxide, actinomycin D, Adriamycin, etoposide, camptothecin, 5-fluorouracil, mitomycin C, and cisplatin. These results showed that DNA strand breaks were sufficient to lead to increased levels of p53. The protein synthesis inhibitor cycloheximide blocks the increase in p53 following DNA damage. The increase in p53 activation in camptothecin treated cells may result, at least in part, from an increased half-life of the protein and consequent increases in intracellular protein concentration. PMID- 8485707 TI - High efficiency gene transfer into primary human tumor explants without cell selection. AB - Preclinical studies with murine tumor models have demonstrated that autologous tumor cell vaccines engineered to secrete certain cytokines in a paracrine fashion elicit systemic immune responses capable of eliminating small amounts of established tumor. These results have engendered much interest in developing this strategy for gene therapy of human cancer. The major limitation to creating genetically modified autologous human tumor vaccines is efficient gene transfer into primary tumor explants, since the majority of human tumors fail to proliferate in long-term culture. Using the retroviral vector MFG in conjunction with short-term culture techniques, we have achieved, in the absence of selection, a mean transduction efficiency of 60% in primary renal, ovarian, and pancreatic tumor explants, and we have developed an autologous granulocyte macrophage colony-stimulating factor secreting tumor vaccine for clinical trials. PMID- 8485708 TI - Overexpression of p53 is a late event in the development of malignant melanoma. AB - Overexpression of the p53 gene product has been observed in a high percentage of malignant melanomas. To evaluate the role of this protein in the development of melanoma, we examined p53 expression in benign, premalignant, and malignant melanocytic lesions. Using the antibodies DO-7 and 1801, which recognize both wild-type and most mutant forms of the p53 protein, we analyzed by immunohistochemical staining 26 benign nevi, 34 dysplastic nevi from patients at low risk for the development of melanoma, 22 dysplastic nevi from patients at high risk for the development of melanoma, 61 primary melanomas (including 15 that arose from dysplastic nevi), and 10 metastatic melanomas. Expression of the p53 protein was not observed in any of the benign or dysplastic nevi. Of the primary melanomas only 3 (5%) demonstrated nuclear staining, whereas 70% of the metastatic melanomas showed a positive reaction for p53. These data suggest that overexpression of the p53 gene product is a late event in the progression of melanoma and consequently indicate that expression of this protein cannot be used as a marker to identify patients at high risk for the subsequent development of melanoma. PMID- 8485709 TI - Suramin: a novel antineoplastic agent with multiple potential mechanisms of action. PMID- 8485710 TI - Ultraviolet radiation-induced DNA damage and its photorepair in the skin of the platyfish Xiphophorus. AB - Fluence response relationships for the induction of DNA damage in the skin of UV irradiated Xiphophorus fish were obtained by quantitative gel electrophoresis of unlabeled DNA following extraction and treatment with an enzyme preparation that makes single strand breaks next to cyclobutane pyrimidine dimers. A buffer containing 7 M urea minimized the degradation of DNA during extraction and gave reproducible results. The shapes of fluence response curves for the production of dimers by sun lamp irradiation (lambda > 290 nm) or 302 nm in the dermis of grown fish were similar. Photoreversal of dimers was readily observed by black light exposure or from the longer wavelengths (> 304 nm) from sun lamps. As expected, the number of pyrimidine dimers/incident fluence in young fish skin was considerably higher on the irradiated side of immobilized fish than it was in swimming (randomly moving) fish, and the shape of the fluence response curves was linear for all wavelengths used lambda > 290, 302, and 313 nm. On the other hand, young fish irradiated from above with lambda > 290 nm showed a less than linear relationship between pyrimidine dimers in their skin and radiation fluence because most exposure occurred on the dorsal rim of fish skin; thus, some cells in that skin were exposed to high fluences while others were not, leading to a heterogenous population of cells. Values of dimers produced were also much less than in immobilized fish. The pigment melanin decreased the number of dimers in the epidermis of grown fish exposed to lambda > 290, 302, or 313 nm, or in the dermis of fish following 302 nm, thus conferring protection against this kind of damage. No dimers were detected in the epidermis of fish exposed to 365 nm. The dimers produced at 302 and 313 nm at tumoricidal exposures correspond to 1 dimer in 10(5) base pairs. PMID- 8485711 TI - Insulin-like growth factor 1 receptors are increased in estrogen-induced kidney tumors. AB - We have previously demonstrated that membrane receptor protein tyrosine kinase(s) activities are higher in estrogen-induced kidney tumors in comparison with such activities in the normal kidney. In the present work we have investigated the growth factor binding sites in estrogen-induced kidney tumor and in normal kidney membranes in an attempt to understand the mechanism of activation of membrane protein tyrosine kinase(s) and their possible relationship to the induction of estrogen-induced tumors. The characteristics of the normal hamster kidney membrane insulin-like growth factor 1 (IGF-1) receptor are similar to those reported for kidney and extrarenal tissues of other rodents. The binding of 125I IGF-1 to the normal kidney or tumor membranes was saturable and dependent on time, protein, pH, and temperature. The binding of 125I-IGF-1 to the tumor membranes was significantly higher when compared to the binding activity of the membranes obtained from age-matched normal kidney. The Scatchard analysis of the binding data of both tumor and normal kidney revealed a single class binding site for IGF-1 with Kd of 1.7 and 1.8 nM and maximum binding capacities of 4150 and 2050 fmol/mg protein, respectively. Therefore, the difference observed in 125I IGF-1 binding between tumor and normal kidney membranes was due to an increase in the number of IGF-1 binding sites with no change in the affinity of receptors for IGF-1. An enhanced level of IGF-1 receptors in tumor membranes also was visualized by autoradiography following affinity labeling of membrane proteins subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under reducing conditions of electrophoresis, two molecular bands of M(r) 240,000 and M(r) 130,000 were evident. The M(r) 130,000 band represents the alpha subunit of IGF-1 receptors, and the M(r) 240,000 band may represent the aggregates of the receptor subunits which were not reduced completely. IGF-1 stimulated normal kidney or tumor membrane protein tyrosine kinase(s) (wheat germ lectin agarose purified membrane proteins) in a dose-dependent fashion. Therefore, the alteration of IGF-1 binding activity of the tumor membrane receptors and stimulation of IGF-1-mediated membrane protein tyrosine kinase activity in tumor tissues suggest that events coupled to this membrane receptor may play a role in estrogen stimulation of renal carcinoma. PMID- 8485712 TI - Phosphorylation of elongation factor 2 in normal and malignant rat glial cells. AB - Certain calmodulin (CaM)-dependent protein kinases phosphorylate substrates have been implicated in regulating cellular proliferation. In this study, CaM dependent phosphorylation has been examined in normal and tumor tissue from rat brain to determine whether differences exist. Using in vitro phosphorylation reactions, we compared endogenous substrates for Ca2+/CaM-dependent protein kinases in rat brain white matter (RBWM), a tissue rich in normal glia, to those of C6 rat glioma cells. A major phosphoprotein having a M(r) of 100,000 was observed in proliferating C6 cells that was not present in RBWM or in nonproliferating cells. Phosphorylation was stimulated by Ca2+ and CaM and inhibited by trifluoperazine. An antibody to elongation factor 2 (EF-2) immunoprecipitated the M(r) 100,000 protein from C6 cells. EF-2 was present in RBWM but was not phosphorylated. Homogenates of RBWM did not phosphorylate exogenous EF-2, which suggested the absence of CaM kinase III activity in normal glial tissue. Furthermore, the addition of purified, exogenous CaM kinase III to homogenates of RBWM resulted in EF-2 phosphorylation. These data demonstrate that a basal level of EF-2 phosphorylation exists in proliferating glioma cells that is markedly diminished or absent in normal glial tissue and is due to the activity of CaM kinase III. PMID- 8485713 TI - Gene expression and cell proliferation in rat liver after 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure. AB - Recently 4 genes (plasminogen activator inhibitor 2, interleukin 1 beta, clone 1, and clone 141) that are transcriptionally or posttranscriptionally responsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been cloned from a human skin keratinocyte cell line. We determined whether these genes were expressed in the livers of Sprague-Dawley rats following exposure to TCDD and whether there was a relationship between expression and hepatic cell proliferation. TCDD was administered by using a dose loading/maintenance regimen to achieve rapid quasi steady-state TCDD liver concentrations of 0.03, 30, or 150 ng/g of liver. Gene expression was determined by Northern analysis using polyadenylated mRNA isolated from liver tissue of male and female animals exposed to TCDD for 1 or 14 days and hybridized with the human complementary DNA clone corresponding to one of the four human TCDD-responsive genes. Under low-stringency hybridization conditions, only the expression of clone 1 could be detected. A dose- and time-dependent expression of this gene was observed in the liver of both male and female rats. Expression of clone 1 was not detected in rats subjected to either a two-thirds partial hepatectomy or exposure to a single administration of the hepatic tumor promoters Wy-14643, carbon tetrachloride, or phenobarbital at doses that induce hepatic cell proliferation. Liver:body weight ratios were elevated in rats exposed to the middle and high TCDD doses. Histopathological observation and analysis of serum enzyme levels indicated no evidence of TCDD-induced liver necrosis. Cell proliferation was evaluated immunohistochemically after 7-day 5 bromo-2'-deoxyuridine administration. No increase in total hepatic labeling index was observed for any of the TCDD-exposed treatment groups compared to controls at week 1 or week 2. An increase in the periportal hepatocyte proliferation labeling pattern was observed in TCDD-treated animals. While these results demonstrate that a human TCDD-responsive gene is expressed in the liver of TCDD-treated male and female Sprague-Dawley rats, the expression of this gene is not linked to hepatic cell proliferation or the sex-specific tumor-promoting activity of TCDD. PMID- 8485714 TI - Inactivation of plasmid reporter gene expression by one benzo(a)pyrene diol epoxide DNA adduct in adult rat hepatocytes. AB - Polycyclic aromatic hydrocarbons such as benzo(a)pyrene diol-epoxide (BPDE-I) cause hepatocellular carcinoma. To identify short-term carcinogen effects, we studied hepatocytes transfected with nonreplicating plasmids, adducted covalently with BPDE-I, varying in promoter structure and encoded reporter gene (beta galactosidase or luciferase). BPDE inactivated gene expression as a first-order function of BPDE concentration in adduction reactions. No evidence of cytotoxicity, diminished coprecipitation and availability, enhanced nicking of supercoiled forms and reduced cellular uptake, or instability of adducted plasmids was observed. At low BPDE:plasmid ratios, inactivation occurred with 1 adduct/plasmid within a target 23-27% of plasmid bases. Using nuclear extracts and BPDE-adducted G-free cassette-encoding plasmids, the fraction of full-length RNA polymerase II-initiated transcripts also declined as a first-order function of BPDE concentration when approximately 3 adducts were distributed among 48% of plasmid bases. These observations suggest that carcinogens such as BPDE block mRNA transcription along DNA templates by forming limited numbers of persistent adducts at coding or noncoding sites. PMID- 8485715 TI - Local control of T2/3 transitional cell carcinoma of bladder is correlated to differences in DNA supercoiling: evidence for two discrete tumor populations. AB - Single cell tumor suspensions were prepared from biopsy and urine samples from 48 patients with muscle invasive transitional cell carcinoma of the bladder. Prior to therapy, samples were irradiated in vitro with the condensation of DNA supercoils measured by the light scattered within a flow cytometer. Six months after completing a course of radiotherapy, the in vitro data were correlated with the presence or absence of local disease. After 12-Gy irradiation, nucleoid extraction and staining with 50 micrograms/ml ethidium bromide, 2 predominant forms of supercoiling behavior were seen. Nucleoids scattered either approximately 10% (Type I) or 35% (Type II) more light than unirradiated controls. Those patients with residual disease showed more Type I behavior (21 of 25; 84%) than those patients clear of disease (9 of 23; 39%) (P = 0.02). It is proposed that the ability of these tumor samples to adopt positive supercoiling after irradiation is related to a stronger association between individual DNA loops and their attachment to the nuclear matrix. This difference in nucleoid response within these tumor samples may be related both to intrinsic cellular radiosensitivity and, subsequently, to clinical radiocurability. PMID- 8485716 TI - Phase I study of amonafide dosing based on acetylator phenotype. AB - Amonafide is extensively metabolized, including N-acetylation to an active metabolite. Prior studies have demonstrated that patients who are fast acetylators of amonafide (and other drugs) have increased toxicity at standard doses of amonafide. The primary objective of this study was to define the recommended phase II dose of amonafide separately for slow and fast acetylators. Twenty-six patients with advanced cancer underwent acetylator phenotyping with caffeine and were assigned to a dose level. Slow acetylators were treated at 375 mg/m2 (daily for 5 days) and had a median WBC nadir of 1600/microliters. Fast acetylators were treated at both 200 and 250 mg/m2, resulting in median WBC nadirs of 5300 and 2000/microliter, respectively. Two patients were not typeable, and two patients appear to have been misphenotyped, one in each phenotype category. Pharmacodynamic analysis yielded a model for nadir WBC including acetylator phenotype, 24-h N-acetyl-amonafide plasma concentration, gender, and pretreatment WBC. We recommend doses of 250 and 375 mg/m2 (for 5 days) for further phase II testing of amonafide in fast and slow acetylators, respectively. PMID- 8485717 TI - Steroid production in different parts of malignant and benign ovarian tumors in vitro. AB - Pieces of ovaries and tumors from 45 patients (19 with malignant epithelial tumors, 14 with benign epithelial tumors, and 12 with normal postmenopausal ovaries) were incubated, and the release of steroid hormones from different parts of the tumors and from the contralateral ovaries was measured. Tumor tissue (mainly tumor cells with a small number of stromal cells), tumor base tissue (more stromal cells than tumor cells), and control ovaries were preincubated in oxygenated 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-minimum essential medium buffer at 37 degrees C for 30 min followed by a 3-h incubation in fresh, oxygenated medium. Progesterone, androstenedione, testosterone, and estradiol were measured in the medium by radioimmunoassay at the end of the incubation period. Malignant tumors released more progesterone and androstenedione than benign tumors or postmenopausal control ovaries. In contrast, benign tumors released more testosterone than malignant tumors or control ovaries. Release of estradiol was low and not significantly different among control ovaries and malignant and benign tumor tissue. Different parts of the tumors differed in steroid hormone release. Tissue samples containing more tumor cells than stromal cells released more progesterone than those with predominantly stromal cells. Thus, malignant tumors had an active steroid secretion. Progesterone was the main steroid released. PMID- 8485718 TI - The glutathione S-transferase mu polymorphism as a marker for susceptibility to lung carcinoma. AB - Glutathione S-transferase (GST) enzymes detoxify carcinogens in tobacco smoke. Interindividual variation in GST function may be related to differences in risk for smoking-related cancer. Leukocytes from 50% of Caucasians lack GST activity toward trans-stilbene oxide (TSO), due to a deletion of the gene for the GST-mu enzyme. Presence of GST-TSO activity in leukocytes has been associated with low risk for lung cancer among cigarette smokers. We sought to determine whether GST activity in lung tissue is determined by the same gene polymorphism and whether it is associated with risk for lung cancer. Subjects were cigarette smokers, identified at the time of lung resection or autopsy in Seattle hospitals. Uninvolved lung tissue was obtained from 35 patients with lung carcinoma and 43 control patients and assayed for GST-mu activity with TSO, for the presence of the GST-mu gene product with an immunological assay, and for the GST-mu gene with Southern blotting. Mailed questionnaires were used to collect information on subjects' smoking histories and exposures which might alter enzyme activity. Interindividual results from the three assays correlated well. Smokers with high GST-TSO enzyme activity present in their lung tissue had a lower risk for lung carcinoma than did smokers with no or low activity (relative risk = 0.30; 95% confidence interval, 0.11-0.79), as did smokers with GST-mu antigen identified in lung tissue versus those with no antigen (relative risk = 0.30; 95% confidence interval, 0.11-0.79). Smokers with both maternal and paternal copies of GST-mu DNA (n = 7) had a lower cancer risk than smokers lacking GST-mu DNA (n = 30; relative risk = 0.35; 95% confidence interval, 0.06-2.10). High GST-mu activity appeared to be associated with a greater decrease in lung cancer risk among 38 heavy cigarette smokers (relative risk = 0.15; 95% confidence interval, 0.03 0.64) than among 38 light smokers (relative risk = 0.61; 95% confidence interval, 0.14-2.60). Presence or absence and number of copies of the GST-mu gene appear to determine activity of the GST-mu enzyme in lung. Smokers with the GST-mu enzyme have approximately one-third of the risk for lung carcinoma of smokers without the enzyme. PMID- 8485719 TI - Comparison of the therapeutic effects of a new arotinoid, Ro 40-8757, and all trans- and 13-cis-retinoic acids on rat breast cancer. AB - A novel arotinoid, 4-((2-(p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl- 2 naphthyl)propenyl]phenoxy))ethyl))-morpholine, was tested in rats bearing established chemically induced mammary tumors. At a dose of 0.35 mmol/kg/day of 4 ((2-(p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthyl)propenyl]phenoxy)ethyl))-morpholine, decreased tumor growth was seen after 2 weeks. By weeks 4 and 5, tumor burdens were decreased to 10-30% of initial values and 50-70% of the animals became free of palpable tumors. Stabilization of tumor size through 15 weeks of treatment was seen in rats given 0.23 mmol/kg/day of the arotinoid. The predominate adverse effects of this compound were dose-dependent weight loss during the first 1-3 weeks, attributed to poor palatability of the food admix as well as flaking of the skin and alopecia at later times. Bone toxicity, a characteristic side effect of retinoids in rodents, was rare with this arotinoid, mainly confined to young rats treated for more than 12 weeks with high doses. In a comparative study, neither all-trans retinoic acid nor 13-cis-retinoic acid had significant antitumor effects at doses that were tolerated by the animals. When all-trans-retinoic acid was administered at 0.08 mmol/kg/day, tumor reduction was seen during weeks 4-6, but treatment was terminated after week 6 due to severe skeletal toxicity and general deterioration in all the animals. Such marked toxicity was not evident with the arotinoid at doses having high antitumor activity. The high efficacy and relatively low toxicity of 4-((2-(p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthyl)propenyl]phenoxy)ethyl))-morpholine suggest that it may be a promising new anticancer agent. PMID- 8485720 TI - The role of active oxygen species and lipid peroxidation in the antitumor effect of hyperthermia. AB - The role of active oxygen species and lipid peroxidation in the antitumor effect of hyperthermia was studied in an experimental rabbit model. VX2 tumors were transplanted into rabbit hind legs, and the effect of hyperthermia on tumor growth was measured at 7 and 14 days after heating. As an index of lipid peroxidation, thiobarbituric acid-reactive substances in the tumor tissue were measured prior to hyperthermia and 3, 6, 12, and 24 h after hyperthermia. Tumor growth in rabbits treated with hyperthermia was significantly reduced, and thiobarbituric acid-reactive substances in the tumor tissue treated with hyperthermia were significantly increased until 6 h after hyperthermia. In addition, alpha-tocopherol in the tumor tissue was significantly decreased after hyperthermia. The antitumor effect of hyperthermia and the increase of thiobarbituric acid-reactive substances in the tumor tissue treated with hyperthermia were significantly inhibited by the administration of superoxide dismutase and catalase or dimethyl sulfoxide. These results suggest that lipid peroxidation mediated by active oxygen species plays an important role in the antitumor effect of hyperthermia. PMID- 8485721 TI - Intraarterial therapy of human glioma xenografts in athymic rats using 4 hydroperoxycyclophosphamide. AB - The addition of chemotherapy, notably using nitrosoureas, in the treatment of patients with glioblastoma multiforme has resulted in only modest improvements in long-term patient survival over the use of surgical intervention and irradiation alone. Intraarterial (i.a.) chemotherapy offers the potential benefit of increasing tumor drug delivery because of first-pass drug uptake, while minimizing systemic drug levels and toxicity. We have now investigated the i.a. therapy of intracerebral human glioma xenografts in athymic rats with 4 hydroperoxycyclophosphamide (4-HC), a preactivated derivative of cyclophosphamide. Athymic male rats were given intracerebral injections of the human glioma line D-54 MG. On Day 5 after injection, the rats were randomized (n = 8-10) by body weight (mean weight, approximately 300 g). In one set of experiments, each group received either i.v. saline, i.a. saline, 6 mg i.a. 4-HC, 6 mg i.v. 4-HC (6 mg), or 12 mg i.v. 4-HC. Intraarterial 4-HC produced significant increases in median survival (Day 24) compared with i.a. saline controls (140% increase), equivalent doses given i.v. (71% increase), and twice the equivalent dose given i.v. (50% increase) (by Wilcoxon rank sum analysis, P < 0.05 is statistically significant). The i.a. maximum tolerated dose was subsequently determined to be approximately 12.5 mg in non-tumor-bearing rats. Further experiments demonstrated a dose-response increase in survival for i.a. dosages of 6, 9, and 12.5 mg with significant improvement when compared with saline controls and 12.5 mg i.v. Pharmacokinetic experiments also demonstrated a significant first-pass uptake advantage for i.a. (versus i.v.) administered 4-HC. The short plasma half-life and marked antiglioma activity of 4-HC, without the need for hepatic activation, suggest a therapeutic application of this drug in the i.a. treatment of brain tumors. PMID- 8485722 TI - Mechanisms of adoptive immunotherapy: improved methods for in vivo tracking of tumor-infiltrating lymphocytes and lymphokine-activated killer cells. AB - Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and lymphokine activated killer cells has been demonstrated to mediate regression of tumors in murine models and in selected patients with advanced cancer. Improved methods for monitoring immune cell traffic, particularly to sites of tumor, are needed to elucidate mechanisms of antitumor activity and optimize treatment protocols. Traditional cell tracking methods such as fluorescent protein labeling and radiolabeling using 111In, 125I, or 51Cr are limited by isotope half-life, leakage or transfer of label from immune cells, and toxicity or altered cell function caused by the labeling process. Labeling with genetic markers allows long-term cell tracking but is laborious to perform and difficult to quantitate. We have used two recently described lipophilic cell tracking compounds (PKH26 and 125I-PKH95) which stably partition into lipid regions of the cell membrane to track immune cells in vivo. Concentrations of each tracking compound which had no adverse effects were determined for a variety of murine TIL and lymphokine activated killer cell functions. Viability was unimpaired at labeling concentrations of up to 5 microM for PKH95 and 20 microM for PKH26. TIL proliferation was unaltered by labeling with up to 5 microM PKH95, 20 microM PKH26, or a combination of 15 microM PKH26 and 5 microM PKH95. In vivo cytotoxic effector function and in vivo therapeutic efficacy of lymphokine-activated killer cells and TIL were also unimpaired by labeling with 20 microM PKH26 or 1 microM 125I-PKH95. Subsequent studies in an adoptive transfer immunotherapy model used 125I-PKH95 to track the biodistribution of TIL in tumor and in non-tumor-bearing animals and PKH26 fluorescence to monitor microdistribution within tissues and distinguish TIL from host T-cells. The results suggest that differential accumulation, selective retention, or proliferation at the tumor site cannot account for the observed pattern of therapeutic efficacy. We hypothesize that a minimum number of TIL must reach the tumor site in order to achieve a demonstrable therapeutic effect. PMID- 8485723 TI - Delivery of radionuclides to pretargeted monoclonal antibodies using dihydrofolate reductase and methotrexate in an affinity system. AB - A novel affinity system for a two-phase delivery of radionuclides to tumor cells has been developed. In the first phase, a nontoxic bivalent monoclonal antibody conjugated to an enzyme is targeted to the tumor cells. In the second phase, a radionuclide-derivatized enzyme inhibitor, specific for the enzyme conjugated to the antibody, is administered. The model system selected for this study is the recombinant human enzyme dihydrofolate reductase (rhDHFR) and its high-affinity competitive inhibitor methotrexate (MTX). MTX was labeled with a radionuclide by covalent attachment of diethylenetriaminepentaacetic acid (DTPA) complexed with 111In. Using the gamma-carboxyl residue of MTX for the attachment of DTPA, binding of the inhibitor to rhDHFR was not affected. The inhibitory activities of nonderivatized MTX and DTPA-MTX were indistinguishable. Human K562 erythroleukemia cells were used to evaluate under in vitro conditions the DHFR MTX affinity system for the delivery of 111In-labeled DTPA-MTX to pretargeted alpha-transferrin receptor antibody-rhDHFR conjugates (alpha-TFR-DHFR). The data demonstrate that the delivery of 111In is dose dependent and highly specific. Under saturating conditions, binding of 111In-DTPA-MTX to alpha-TFR-DHFR-treated cells was 14-fold higher than to cells treated with nonconjugated alpha-TFR antibody. Further experiments indicated that the low level of nonspecific binding of 111In-DTPA-MTX was comparable to that of 111In-DTPA, known for its complete extracellular distribution and rapid clearance through the kidneys. Based on the data of this study, antibody-conjugated rhDHFR and radionuclide-labeled DTPA-MTX complexes provide components for an alternative radioimmunotherapeutic approach that can be expected to result in improved tumor tissue ratios of both the targeting moiety and the radionuclide-labeled derivative as compared to current approaches. PMID- 8485724 TI - Expression of HLA class I antigens in sporadic adenomas and histologically normal mucosa of the colon. AB - The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, inasmuch as it may allow tumors to escape immune surveillance. We have observed reduced expression of HLA antigens in sporadic colon cancer and adenomas from familial adenomatous polyposis patients. We now studied the expression of HLA class I antigens in patients with sporadic adenomas, which are precursors of colorectal cancer. Expression of HLA class I antigens was studied by immunohistochemistry in (a) sporadic colon adenomas, (b) histologically normal mucosa distant from the adenomas, (c) histologically normal colonic mucosa from patients with history of sporadic colon adenomas, and (d) colonic mucosa from normal subjects. HLA class I antigen expression was moderately reduced in 56% and severely reduced in 44% of the adenomas; this reduction was significant when compared to controls (P < 0.0001). The reduction of HLA class I expression in adenomas was related to the grade of dysplasia of the adenomas. HLA class I expression of normal appearing mucosa was decreased in 76% of patients with adenoma (P < 0.0001) and in 54% of patients with history of adenoma (P < 0.005) compared to normal controls. These changes were antigen specific, inasmuch as the expression of carcinoembryonic antigen, a surface antigen, was not affected. Our findings suggest that reduced HLA class I expression is an early event in the cell transformation process from normal to neoplastic state, preceding in many cases the onset of histological changes. HLA class I could be potentially used as a premalignant marker in the colon. PMID- 8485725 TI - Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression. AB - Meningioma is a common tumor of the central nervous system which displays morphological heterogeneity. In order to determine whether this phenotypic variability is associated with distinct or overlapping genetic lesions, we compared genotypes at several loci defined by allele length polymorphism in tumor and normal tissues from patients with meningioma. In particular, we concentrated on loci on chromosomes 22 and 10 because these genomic regions have previously been shown to be altered in the former in sporadic and familial meningiomas and in the latter as a late stage event in progression of another common brain tumor, astrocytoma. We examined 38 tumors which were classified as benign, atypical, or malignant by morphological criteria, invasive characteristics, or both. We found that loss of heterozygosity (LOH) for loci on chromosome 22 occurred in 5 of 15 benign, 2 of 2 atypical, and 5 of 10 malignant meningiomas. Similar alterations of chromosome 10 were found in 0 of 20 benign, 1 of 2 atypical, and 4 of 13 malignant meningiomas. Among the malignant tumors, LOH for loci on chromosome 10 occurred in 2 of 4 morphologically malignant tumors and in 2 of 4 morphologically and invasively malignant tumors. In contrast, LOH was not observed for any of the 5 informative tumors classified as malignant by invasive characteristics only. LOH for loci on chromosome 22 accompanied (but was not restricted to) allelic loss of loci on chromosome 10. These data suggest that the progression of meningiomas from arachnoidal cells to the morphologically malignant phenotype may, in part, entail the loss of a tumor suppressor gene(s) on chromosome 22 early in the process and that this may be compounded by alterations of chromosome 10, the LOH of which is associated with morphological signs of malignancy. PMID- 8485726 TI - Human epithelial ovarian cancer allelotype. AB - To determine which chromosomes and chromosomal regions contain putative tumor suppressor genes important for human epithelial ovarian cancer, we performed loss of heterozygosity (LOH) studies on 37 primary epithelial ovarian tumors. Using 70 polymorphic markers, we examined all chromosome arms (excluding acrocentric arms) on all specimens. Our findings show a high frequency of LOH for the following chromosome arms: 5q (43%); 6p (62%); 6q (57%); 7p (36%); 8p (40%); 9q (54%); 13q (56%); 14q (47%); 15q (36%); 17p (81%); 17q (76%); 18q (43%); 21q (36%); and 22q (71%). When separated into low and high grade tumors, there were statistically significant differences of LOH for the following chromosome arms: 6p (29% versus 70%); 13q (0% versus 72%); 17p (33% versus 90%); and 17q (29% versus 87%). No statistically significant difference was found between different histological subtypes. The average fractional allelic loss for low grade tumors was 0.17 versus 0.40 for high grade and 0.35 for all tumors. In an effort to more specifically localize common regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 13 (5 markers); chromosome 17 (8 markers); and chromosome 6 (8 polymorphic markers). No tumor showed deletion of only a portion of chromosome 13. When any informative marker for chromosome 13 showed loss, all markers showed loss. Similarly, the tumors of most patients demonstrated LOH of all informative markers that map to chromosome 17; however, regional deletion of 17p markers was observed in 3 tumors. Twelve tumors demonstrated regional deletions of portions of chromosome 6. These tumors suggest that at least 2 regions of chromosome 6 are important for ovarian epithelial carcinogenesis. One region appears to be on distal 6q and a second region is near the centromere of chromosome 6 proximal to the HLA locus. PMID- 8485727 TI - Concerted control of multiple histone promoter factors during cell density inhibition of proliferation in osteosarcoma cells: reciprocal regulation of cell cycle-controlled and bone-related genes. AB - Cell density-induced growth inhibition of osteosarcoma cells (ROS 17/2.8) results in the shutdown of proliferation-specific histone H4 and H2B genes and the concomitant up-regulation of several osteoblast-related genes. In several respects, this reciprocal regulatory relationship is analogous to the proliferation/differentiation transition stage during development of the bone cell phenotype in normal diploid osteoblasts. Here, we comprehensively analyzed the promoter binding activities interfacing with key regulatory elements in the cell cycle-dependent histone and bone-specific osteocalcin genes. Similarly, we examined factors interacting with a series of general transcription regulatory elements that are present in a broad spectrum of promoters. The results show that histone promoter binding activities HiNF-D, HiNF-P/H4TF-2, H4UA-1, and OCT-1, as well as AP-1 activity, are proliferation dependent. These factors decline coordinately during the cessation of proliferation in both ROS 17/2.8 bone tumor cells and normal diploid osteoblasts. Collective down-regulation of these trans activating factors occurs in both cell types within the physiological context of constitutive regulation of ubiquitous transcription factors (Sp1, ATF, and CCAAT binding proteins). In addition, during growth inhibition of ROS 17/2.8 cells we observe a complex series of modifications in protein/DNA interactions of the osteocalcin gene. These modifications include both increased and decreased representation of promoter factor complexes occurring at steroid hormone response elements as well as tissue-specific basal promoter sequences. These results demonstrate cell growth regulation of the promoter factors binding to the proliferation-specific histone and tissue-specific osteocalcin genes during the cessation of proliferation. PMID- 8485728 TI - Selectively down-regulated expression of major histocompatibility complex class I alleles in human solid tumors. AB - We studied the expression of major histocompatibility complex (MHC) class I molecule in 52 ex-vivo tumor samples comprising 29 ovarian, 15 lung, 1 breast, and 4 colon carcinomas; 1 midgut carcinoid; and 2 malignant mesenchymal tumors obtained from surgical specimens or from malignant effusions. The allelic products were visualized in untreated and interferon gamma + tumor necrosis factor alpha treated aliquots of tumor cells and in the patient's blood lymphocytes by the one-dimensional isoelectric focusing method. Generally, the tumor cells contained lower amounts of MHC class I molecules compared to the lymphocytes. In vitro exposure to interferon gamma and tumor necrosis factor alpha elevated the level of MHC class I expression in 24 of 52 tumors and corrected the assembly defect seen in 2 cases. In 20 tumors one or several human leukocyte antigen alleles were undetectable even after cytokine treatment. Correlation was seen with the grade of differentiation; the proportion of tumors with selective losses in poorly, moderately, or well differentiated tumors were 16 of 30, 3 of 13, and 1 of 9, respectively. Selective losses occurred in ovarian carcinoma cells collected from malignant effusions (12 of 22, 54%) but not in 7 primary tumors. In primary lung carcinomas the frequency was 36% (5 of 14 cases). Thirty-nine patients were serologically typed; thus the MHC alleles on the tumor cells could be identified. In this panel of tumors 30 human leukocyte antigen alleles were represented. Among these the expression of 15 was found to be down regulated in some but not all tumors of the same histology. PMID- 8485729 TI - Heterocyclic amines in cooked foods: possible human carcinogens. PMID- 8485730 TI - Introduction II: American Cancer Society Research Workshop on Cancer and Nutrition. PMID- 8485731 TI - Funding mechanisms for research through the National Cancer Institute. PMID- 8485732 TI - Funding mechanisms for research through the American Cancer Society. PMID- 8485733 TI - Can we really derive etiology from human-based studies? PMID- 8485734 TI - Diet, nutrition, and cancer: development of hypotheses and their evaluation in animal studies. AB - Research in diet, nutrition, and cancer is multidisciplinary. As a result there are many factors to consider in the conceptualization and design of experiments that may not be readily apparent to someone entering this field. In this article issues are identified that should be considered in the development of hypotheses about the effects of diet and nutrition on the carcinogenic process and the evaluation of these hypotheses using animal models. The questions considered are: what comprises an acceptable rationale for diet, nutrition, and cancer experiments in which animal models are used; what factors should be considered in the design of these experiments; and what constitutes a mechanistic component in such animal studies. PMID- 8485735 TI - Use of cell and organ cultures in the identification and characterization of agents that modify carcinogenesis. PMID- 8485736 TI - Report of group A of the American Cancer Society Research Workshop on Cancer and Nutrition: panel on human studies. PMID- 8485737 TI - Report of group B of the American Cancer Society Research Workshop on Cancer and Nutrition: panel on animal studies. PMID- 8485738 TI - Report of group C of the American Cancer Society Research Workshop on Cancer and Nutrition: panel on cell and organ culture studies. PMID- 8485739 TI - Treatment of a malignant stricture after esophagojejunostomy by a self-expanding metallic stent. AB - Gianturco self-expanding metallic stents (GSs) were placed across an esophagojejunostomy which had become strictured secondary to recurrent anastomotic gastric cancer. Placement of the GS enabled the patient to take liquid food and swallow saliva, though only for a short period of time. One month after placement, the stented lumen restrictured with a markedly irregular contour. The patient's clinical status deteriorated with eventual occlusion of the stented anastomosis. The patient died of renal insufficiency 80 days after placement of the stent. There are some questions concerning the stability of applying the Gianturco-type bare stent to the digestive tract. In the future, more suitable stents will have to be developed. PMID- 8485740 TI - Delayed fatal cardiac perforation by an indwelling long introducer sheath following transjugular intrahepatic portocaval stents (TIPS). AB - Iatrogenic cardiac perforation is a recognized complication of central venous catheterization. We report a fatal complication by a 10F introducer sheath which was left in place and resulted in perforation of the right atrial wall 8 h later. This case is reported to emphasize the increased risk of cardiac perforation from large caliber rigid sheaths which should be withdrawn immediately after completion of the procedure. PMID- 8485741 TI - A new curved peel-away sheath for central venous catheter placement. AB - A new 10F peel-away sheath with a preformed curve is now available. The procedure for insertion of central venous catheters remains the same, with the new curved sheath replacing the straight version. In our experience, this modification facilitates the placement of central venous catheters and decreases the incidence of catheter tip malposition and kinking. PMID- 8485742 TI - Bird's nest filter placement within an enlarged hemiazygos vein for prevention of pulmonary embolism. AB - Thrombosis of the inferior vena cava (IVC) may result in considerable enlargement of paravertebral, azygos, and hemiazygos collateral veins that may in turn serve as pathways for thromboemboli to the pulmonary circulation. Herein we describe the transfemoral placement of a Bird's Nest filter within an enlarged hemiazygos vein to provide prophylaxis against pulmonary embolism in a patient with right femoral venous thrombosis who could not tolerate systemic anticoagulation. There had been earlier transjugular placement of a Greenfield filter within the suprarenal IVC. PMID- 8485743 TI - Transosseous air contrast CT-guided needle biopsy of a cystic neoplasm. AB - CT-guided fine-needle aspiration biopsy of a metastasis from an ovarian cystadenocarcinoma was performed using air contrast and a transosseous approach. Air contrast allowed identification of a papillary projection within the cyst, and the transosseous approach permitted direct and easy access to the lesion. PMID- 8485744 TI - Re: Selecting the right technique to reform a reverse curve catheter (Simmons style): critical review. PMID- 8485745 TI - The interventional radiologist's training in The Netherlands. PMID- 8485746 TI - Percutaneous thrombectomy of the acutely thrombosed dialysis graft: in vitro evaluation of four devices. AB - Percutaneous recanalization of completely thrombosed hemodialysis grafts was simulated in a flow model. Thrombus removal was performed by 1) a Trac-Wright catheter; 2) an ultrasound-driven, oscillating probe aspiration thrombectomy (US OAT) device; 3) an electric motor-driven oscillating probe aspiration thrombectomy (EM-OAT) device; and 4) a rotating spiral aspiration thrombectomy (RAT) device. All devices were able to restore a continuous lumen of the shunt model within 1-5 min, but residual layers of wall-adherent thrombi remained attached, particularly to the inner curvature of the shunt loop. Clot removal rate was 95% for the Trac-Wright catheter, 73% for the US-OAT device, 68% for the EM-OAT device (straight tip catheter), 88% for the EM-OAT device (angulated tip catheter), and 51% for the RAT device. Effluent particle rates for particles > 100 microns were 3.6% for the Trac-Wright catheter, 0.6% for US-OAT, and less than 0.1% for the other devices. Compared with the Trac-Wright catheter, the balance of clot-removing efficiency and creation of effluent particles favored the electric oscillating device with the angulated tip catheter, which had a slightly reduced, but still efficient, clot-removing capability and produced almost no effluent particles. PMID- 8485747 TI - Renal vein renin analysis: limitations of its use in predicting benefit from percutaneous angioplasty. AB - Two hundred forty-four consecutive patients (mean age 61 years), including 123 who had technically valid renal vein renin (RVR) analysis and 121 without RVR data, underwent technically successful percutaneous renal artery angioplasty (PTRA). They were retrospectively examined to evaluate the utility of RVR analysis in identifying renal hypertension (RVH), predicting benefit from PTRA, and determining if the lack of knowledge of renin levels significantly affected clinical outcome after PTRA. Abnormal RVR values were associated wtih clinical benefit after PTRA in 62 of 93 patients (67% sensitivity, 20% specificity, 72% positive predictive value). Clinical improvement following PTRA occurred in 31 of 37 patients with normal pre-PTRA RVR values (16% negative predictive value). RVR analysis correctly identified 86 of 117 patients with renovascular hypertension (74% sensitivity, 16% negative predictive value). Improved blood pressure (BP) control occurred in 72% with abnormal RVR analysis and 66% of the 121 patients without RVR data (p > 0.1). We conclude that the very low negative predictive value significantly limited the use of RVR analysis in this elderly (mean age 60 years) patient population with a high incidence of mild renal functional impairment (mean serum creatinine 1.4 mg/dl) and bilateral renal artery stenosis (38%). The lack of pre-PTRA renin data did not significantly affect clinical outcome. If RVR data were relied upon as the exclusive selection criterion in patients of this type, many would be prevented from having the benefit of cure or improvement by PTRA. PMID- 8485748 TI - Percutaneous treatment of hepatic cysts by aspiration and sclerotherapy. AB - We treated 35 patients who had hepatic cysts (30 congenital cysts, 5 hydatid cysts) with percutaneous puncture and sclerotherapy. After puncture and drainage of the cyst, a 95% alcohol solution was instilled as sclerosing agent into the cystic cavity. In all the patients, cyst puncture and drainage was successful. Follow-up in all cases was at least 12 months. In three uncooperative patients, cysts recurred due to incomplete sclerosis of the lining epithelium of the cyst wall. No major complications were encountered in all cases. All congenital cysts were treated on an outpatient basis. Patients with hydatid cyst were hospitalized for 48 h after puncture and aspiration. In our opinion, percutaneous drainage and sclerosis of congenital hepatic cysts can be considered an effective alternative to surgical treatment. PMID- 8485749 TI - Embolotherapy for persistent hemoptysis: the significance of pleural thickening. AB - Elective embolotherapy for recurrent hemoptysis was evaluated for its effectiveness. Forty embolotherapeutic procedures were performed in 30 patients. In the short term, complete hemostasis was achieved in 16 of 40 procedures (40%) and significant improvement in another 16 procedures (40%). Long-term, complete hemostasis was achieved in 14 of 34 procedures (41%) and significant improvement in 12 (35%). Embolotherapy was consistently more effective in patients who had no pleural abnormalities compared with those with pleural thickening. Long-term complete hemostasis was achieved in 7 of 10 procedures (70%) for the patients without pleural thickening and only 7 of 24 (29%) in patients with pleural thickening. Thus, pleural abnormalities negatively influence long-term effectiveness of embolotherapy. PMID- 8485750 TI - Ultrasound-monitored laser angioplasty: preliminary clinical results. AB - A novel coaxial catheter system for ultrasound (US)-guided, pulsed laser angioplasty was tested clinically in 4 patients with stenoses of the femoral and external iliac artery. The mean lesion length was 1.3 +/- 0.4 cm. The 9F multifiber laser catheter incorporated a 4.8F commercial intravascular US catheter and can be guided over a 0.014 inch wire. Laser angioplasty alone reduced the mean degree of stenoses from 84 +/- 8% to 47 +/- 10%. Though laser induced artifacts compromised detailed US monitoring during laser firing itself, the system proved to be clinically useful as assessment of laser effects and measurement of the severity of residual stenoses was possible immediately after laser irradiation. PMID- 8485751 TI - The mechanical properties of guidewires. Part III: Sliding friction. AB - Stiffness is always one of two factors that determine frictional resistance. The other factor, the coefficient of friction, depends on the surface characteristics. Teflon coating reduces the sliding friction to one-half, and a hydrophilic plastic coat to about one-sixth compared with steel. PMID- 8485752 TI - Application of a self-expanding metallic stent to a strictured esophagojejunostomy. AB - We placed a Gianturco self-expanding metallic stent across the recurrent stricture of an esophagojejunostomy in a patient with gastric cancer. Though excellent passage of food resulted, intractable reflux occurred. Two months later the patient succumbed to recurrent tumor. At autopsy, the stent was patent and was partially covered by esophageal mucosa. There were narrow but deep ulcers around the stent hooks. The Gianturco metallic stent may provide an additional option for treating recurrent enteric strictures after other methods fail. Further refinements of the technique appear necessary. PMID- 8485753 TI - [Intercellular communication and signal transduction mechanisms]. AB - Cells in multicellular organisms coordinate their functions by signalling molecules serving as means of communication. Specific receptors enable transduction of chemical information from extracellular environment into a cell. Inside the cell the signal is multiplied and transduced further by intracellular signalling molecules and enzymatic cascades. Phosphorylation of proteins on tyrosine, serine or threonine residues, guanosine triphosphate binding by special G proteins and regulation of DNA transcription seem to be the most important biochemical mechanisms of signal transduction. Products of cellular protooncogenes are involved in all levels of signal transduction, the detailed knowledge of signal pathways is therefore important for our understanding of pathophysiology of malignant disease and strategies for the therapeutic use of growth factors in oncology and haematology. PMID- 8485754 TI - [The sleep apnea syndrome. Basic diagnostic and therapeutic possibilities]. AB - The sleep apnoea syndrome (SAS) involves impaired regular breathing during sleep. It causes poor quality sleep and thus subsequent somnolence in daytime, it leads to periodic oxygen desaturation and has serious cardiovascular consequences. The authors describe methods used for the diagnosis and quantification of the intensity of SAS which they used (all-night extended polysomnography, ambulatory equipment MESAM 4 and afternoon polysomnography) and they list also the main therapeutic procedures used in SAS. PMID- 8485755 TI - [Lyme carditis]. AB - Lyme borreliosis, a systemic disease, described as a new nosological unit as late as in 1976, has called for special attention in particular during the past few years. The author concentrated his attention on affection of the heart, and based on analysis of many publications in the world literature, he submits a review on Lyme carditis which comprises the clinical picture, diagnostic possibilities and treatment. In the conclusion he indicates possible ways how to investigate the disease the course and prognosis of which are the subject of open discussion. PMID- 8485756 TI - [Rapidly progressing glomerulonephritis with antibodies to glomerular capillary basement membrane]. AB - Antiglomerular basement membrane glomerulonephritis was diagnosed in 14 patients (6 men and 8 women) aged 20 to 59 years. Five patients were found to have Goodpasture s syndrome. 5 rapidly progressive glomerulonephritis. 1 nephrotic syndrome, and 1 had mild glomerulonephritis. Blood pressure, proteinuria and haematuria were not severe in most patients. In 10 patients, the diagnosis was not established before end-stage renal failure had developed. Four patients died of lung haemorrhage, in 3 the haemorrhage was controlled by the treatment, in 3 renal failure without lung haemorrhage occurred, and in 3 renal function improved or was stable. The prognosis improved significantly after plasma exchange together with immunosuppression had been introduced. PMID- 8485757 TI - [Fatty acid composition of plasma lipids in hyperlipidemia associated with ischemic heart disease]. AB - The authors compared plasma lipid and lipoprotein values and the fatty acid composition in plasma lipids of a group of 38 men with primary hyperlipoproteinaemia (HLP) type II B and IV with a history of myocardial infarction (IM) and in a control group of 63 men with the same type of HLP without a history of ischaemic heart disease (IHD). Hyperlipidaemic subjects after IM differed from controls by the apolipoprotein (apo) B concentration in LDL lipoproteins and by the composition of fatty acids in plasma phosphatidylcholine (PC) and triglycerides (TG). In the discriminating function which makes it possible in the given group of patients to classify correctly hyperlipidaemic subjects after IM and without detectable IHD the independent variables are apo-B concentration in LDL, apo-A-I in plasma, eicosapentaenoic acid in TG, gamma-linolenic acid in cholesterol esters and stearic and oleic acid in PC. These findings confirm the practical value of assessment of apolipoproteins for detection of hyperlipidaemic subjects with a specially high risk of IHD and indicate also the role of essential FA in the pathogenesis of IM. PMID- 8485758 TI - [The importance of catecholamine determination in athletes]. AB - During a physical as well as mental load as a rule sympathoadrenal activation occurs which leads to a rise of catecholamine plasma levels and their increased excretion. The author investigated changes of plasma catecholamines and their urinary excretion during different experimental conditions in the laboratory and in field work. These changes were assessed after different loads in trained and not trained subjects and the effect of different types of stress was investigated. As to stressing stimuli, the authors reports in the present work on the effect of hypoxia, dehydration, psychological stress, anticipation stress and the combined effect of stress and biorythms. PMID- 8485759 TI - [Sleep apnea syndrome--serious complications in a female patient treated with psychopharmaceutic agents]. AB - The authors present the case-history of a patient treated in the past on account of depressive syndrome who suffered repeatedly from somnolence or even unconsciousness with dyspnoea which called for hospitalization in an anaesthesiological and resuscitation department. The repeatedly expressed suspicion of attempted suicide by drugs was always ruled out by toxicological examination. Based on the clinical picture a preliminary diagnosis of the sleep apnoea syndrome was established confirmed later by polysomnographic examination. The evoking factors of the mentioned serious complications were probably respiratory infections and psychiatric medication, in particular hypnotics- flunitrazepam and triazolam. PMID- 8485760 TI - [An acute care response to chronic care: the American perspective]. AB - American medical care has been characterized by an acute care and surgical orientation. This acute care focus has been reinforced by advances in infectious diseases and cardiology in the years since World War II. The success in acute care medicine, however, has resulted in a larger number of Americans who are older and suffering from chronic disease. Despite these demographic developments, there is a general inattention to chronic and long term care in medical education. Such a focus is needed because unlike acute care medicine which is dependent upon diagnostic categories, the provision of long term care is dependent upon functional status. Ethical considerations in long term care are also different than acute care. While the autonomy ethic is predominant in acute care settings, the needs of the chronically ill might be better addressed with a communitarian ethic of care. The autonomy ethic distorts the doctor-patient relationship most notably in chronic care by isolating the dependent patient from a community of care. The current euthanasia debate in the United States is symptomatic of the health care system's inability to provide adequate chronic, long term and palliative care to patients in great need. PMID- 8485761 TI - [The physician and the anxious child]. AB - The work is based on the conviction that anxiety and its control is a primary problem of man on Earth. Adults who are emotionally attached to a child feel the necessity to protect him. There exists also a syndrome of excessive anxiety and so-called untreatable children. The anxious child can easily succumb to panic: inducing moments are e.g. all medical practices which restrict free mobility or enforce an unusual position of the body. Anxiety is a permanent and to a considerable extent genetically conditioned character trait. Psychologists include it among so-called hard personality traits. The author mentions auxiliary provisions to help anxious children: 1. assurance, 2. training how to use economically his own forces and 3. building a system of safety measures. The author gives an account of principles for dealing with parents of anxious children. PMID- 8485762 TI - [Recent advances in clinical cytogenetics]. AB - The development of cytogenetics in recent years revealed some new and even surprising findings some of which seem to be at variance with accepted rules of this discipline. The submitted paper gives a review of contemporary knowledge of the problem of imprinting, somatic mosaicism, micro-deletion syndromes, unbalanced aberrations without phenotypic manifestations and it mentions also some aspects of fragile X. PMID- 8485763 TI - [Recent advances in clinical aspects of infectious hepatitis]. AB - A review of recent advances in the diagnosis, clinical course, complications and treatment of hitherto known types of viral hepatitis (VHA, VHB, VHC, VHD and VHE). The most serious complication of hepatitis is fulminant hepatic failure. The only effective drug in some types of viral hepatitis is interferon alpha 2a. PMID- 8485764 TI - [Endothelin--a vasoactive peptide of endothelial cells]. AB - Endothelin is a recently discovered peptide which is formed in the endothelial layer of the vascular wall and is released, following different stimuli, into the neighbouring smooth muscle layer of blood vessels and into the vascular lumen. By its effects on the regulation of the vascular tonus endothelin could play a part in regulating the function of various organ systems. The submitted paper gives a brief account on contemporary knowledge regarding the formation, elimination and biological effects of endothelin. The authors discuss also the potential physiological and pathophysiological role of this peptide. PMID- 8485765 TI - [Initial experience with the transjugular renal biopsy]. AB - Transjugular renal biopsy is a new diagnostic method used for collection of tissue specimens for morphological examination in some indicated cases where the use of the standard percutaneous technique involves risk. The method has not been used so far in Czechoslovakia. PMID- 8485766 TI - [Antigens for the ELISA test for serodiagnosis of Helicobacter pylori infection]. AB - Semipurified urease and outer membranes of Helicobacter pylori were isolated and used as antigens for the construction of new ELISA tests for the serodiagnosis of infections caused by this microorganism. The highest discriminating capacity between infected and not infected subjects was obtained by the test detection of IgG antibodies against the urease antigen which reached a 100% sensitivity, 90% specificity, a 100% negative and 91% positive predictive value. Examination of sera of healthy children and blood donors revealed the possibility of asymptomatic infection and an increase of specific antibody levels with age. PMID- 8485767 TI - [IgG antibodies to Gastrospirillum hominis and Helicobacter pylori]. AB - In conjunction with an investigation extending over several years, focused on the understanding of the importance of Helicobacter pylori in inflammatory gastric disease, the authors examined a group of 1242 patients. In fifteen they detected by microscopic examination the presence of helical bacteria described in the literature as Gastrospirillum hominis. The cultivation test was not positive. In three patients in addition to these bacteria also the presence of Helicobacter pylori was detected. Sera of eight patients with Gastrospirillum hominis were investigated by the ELISA test Helico-G f. Porton Cambridge; antibodies against Helicobacter pylori were found in three patients (incl. two with the concurrent presence of G.h. and H.p.). In sera of the remaining five patients antibodies were not detected. PMID- 8485768 TI - [Sorbitol-negative E. coli 016 in a 10-year-old child diagnosed with hemolytic uremic syndrome and in his asymptomatic father]. AB - In Escherichia coli strains isolated from faeces and smears from the rectum in haemolytic-uraemic syndrome of a child and healthy relatives the authors assessed the biochemical activity, antigenic characteristic, sensitivity to twelve antimicrobial substances and factors of virulence. Sorbitol negative strains were isolated from the ill child and his father. The strains belonged into serogroup 016. The remaining strains were sorbitol positive. They belonged into serogroups 02, 012 and 019. Nineteen sorbitol negative strains of E. coli from the sick child caused mannose sensitive agglutination of chicken and guinea pig erythrocytes, they produced colicin V and aerobactin. Except for one strain they were serum resistant. Fourteen strains induced the oedema on the foot of mice and eleven produced a lethal effect in mice. Except for three ampicillin resistant strains the remaining were sensitive to the examined antibacterial substances. Two sorbitol negative strains of E. coli isolated from the asymptomatic father produced aerobactin and one strain was serum resistant. PMID- 8485769 TI - [Testing the sensitivity of opportunistic agents of mycoses to antimycotic drugs in vitro]. AB - The authors tried to standardize the method of assessment of the minimal inhibitory concentration (MIC) of antimycotics for the evaluation of the sensitivity of opportunistic causal agents of mycoses. They paid attention to factors which cause deterioration of the reproducibility of tests and lead to intra- and interlaboratory variability of results. In conjunction with this the authors drew attention to the lack of uniformity of views on the application of these tests in clinical practice. In the author's view the reservation pertaining in particular to an inadequate correlation of results in vitro and in vivo do not cast doubts on the expedience of laboratory assessment of sensitivity. Testing of systemic antimycotics with a low pharmacotherapeutic index and a relatively high frequency of secondary resistance is particularly justified. In those instances assessment of MIC values is a significant component of monitoring of adequate antifungal chemotherapy, in particular when antimycotics are administered for prolonged periods to patients with altered immunity. PMID- 8485770 TI - [The epidemic process in infections before and after active immunization. I. Comparison of long-term monitoring of the disease with a simple mathematical model]. AB - In the first part of this paper the authors used for demographic data and morbidity data concerning measles, parotitis, rubella and chickenpox in the Sokolov district a model of exponential distribution, in particular its distribution function. The authors introduced the concept of mean population year. They tested the theoretical assumption that in different infections in long term average the annual number of infected subjects is equal and equals the mean population year. They found that the delta parameter which determines the shape of the exponential regression curve and is the measure of the rate of spread of a given infection, expressed at the same time numerically by the number of mean population years the mean number of susceptibles which remain permanently in a given population. PMID- 8485771 TI - [Relation between the level of infection in Ixodes ricinus with Francisella tularensis and the level of bacteremia in the host]. AB - The dynamics of bacteremia on white mice subcutaneously infected with an inoculum of 100 and 10 cells of F. tularensis (strain 273) was compared in two parallel experiments. The rise of bacteremia was relatively uniform, about 3 logarithms a day in both groups of animals, so that it reached values of 10(9)-10(10) cells per 1 ml of blood ante finem. Larvae of Ixodes ricinus were fed on white mice in different stages of bacteremia, so that groups of ticks with different degrees of infection were obtained. Our results of quantitative examination show an evident correlation between the degree of bacteremia of the host and the degree of infection of ticks. The highest values of positivity 10(6)-10(7) cells were recorded in larvae, which finished their feeding on the day of the host's death, during the time when bacteremia was reaching the highest degree 10(10) cells per ml of the blood. Persistence of the agent in the organism of infected larvae could be observed up to hatching, under given experimental conditions one month after infection. In nymphs developed from larvae with the highest degree of infection this ability was preserved in about one third of individuals still after 5 months of starvation. In ticks with low degrees of infection it disappeared during the experiments. PMID- 8485772 TI - [Are enteroviruses the causal agents of acute enteritis in humans?]. AB - Based on assembled data from the literature and oral communications as well as findings in the laboratory, the author concludes that an enteroviral aetiology of diarrhoeal diseases can be taken for granted in many instances. Enteroviral gastritis is not frequent nor serious and is usually not encountered in winter but rather in summer under conditions with a higher standard of hygiene. The ratio of enteroviruses in epidemics of gastroenteritis and in the aetiology of enteritis within the framework of epidemics with other manifestations of enteroviral disease is very variable and there is no generally valid frequency which could serve for orientation. Virological and serological diagnosis of enteroviral diarrhoea would not be expedient in winter, it is, however, useful in summer and in epidemics affecting neonates and young children. In general, less attention is paid to an enteroviral aetiology or diarrhoea, as compared with thorough assessment of an enteroviral aetiology in severe forms of the disease. Attention is drawn to the usefulness of a more detailed investigation of properties of strains of polioviruses isolated from patients with diarrhoea. PMID- 8485773 TI - [Infectious diseases yesterday and today]. AB - The authors present examples demonstrating that in the last decades we witnessed the discovery of new nosological units and their infectious agents, the detection of the infectious origin of "old" diseases the aetiology of which was still recently obscure, infectious attacks of people by diseases which were considered animal infectious only, as well as the more frequent incidence of opportune infections due to impairment of the immune state of the human organism. These changes have many reasons such as the development of properties of microorganisms, lifestyle changes of the human population, advances in medicine, and last but not least improving microbiological diagnosis. Attention is drawn to the fact that even in a time when so-called diseases of civilization are in the foreground of interest our awareness of infectious diseases must not slacken. Only all-round international surveillance can prove successful. PMID- 8485774 TI - [The epidemic process in infections before and after active immunization. II. Changes in the number of susceptible individuals in the population during a natural epidemic and its control by active immunization]. AB - Based on the long-term follow-up of the incidence of some infectious diseases in the district and calculations of the actual number of infected subjects, the authors present an estimate of the ratio of susceptible and immune subjects during the unimpaired epidemic process. The epidemic process develops from the lowest range of immune subjects and stops at the highest range. The highest range thus gives the ratio of immune subjects which must be achieved or maintained by active immunization to achieve elimination of a given infection. The authors demonstrate on the model infection the mechanism by which after immunization the shift of infections to higher age groups occurs, and during introduction of the infection not only contact infections occur, but epidemic incidence develops. The restoration of some infections after years of elimination is to a restricted extent a natural phenomenon and does not imply failure of active immunization. PMID- 8485776 TI - [Neurilemmoma of the esophagus imitating carcinoma of the thyroid isthmus]. AB - Fine needle aspiration cytology of a "stone hard" nodule in isthmic thyroid region of a 56-year old woman yielded unusual spindle and polyploid cells in a relatively monomorphic inflammatory background. Finding was suspicious of malignancy. Differential diagnosis of reparative inflammatory changes, anaplastic or medullary carcinoma was considered. During the operation a tight connection of the tumour with oesophageal wall as well as with thyroid was discovered. Biopsy proved the tumour to be a neurilemmoma originating in the oesophageal wall. Most of the tumour cells were S-100 protein positive. Comparison of the cytologic smears and biopsy slides proved the unusual cells to be of tumour origin. PMID- 8485775 TI - [Cytologic diagnosis of medullary carcinoma of the thyroid gland]. AB - Over a five year period 50 malignant tumours (3.8% of investigations) has been histologically proved in a group of 1378 patients who underwent fine needle aspiration biopsy of thyroid. Five of these were medullary carcinomas (0.38% of investigation, 10% of malignancies). During revision and cytohistological correlation the most important cytologic diagnostic features for the sequential diagnosis of medullary carcinoma especially in cases without indicative clinical symptomatology have been checked. The following proved to be indicative especially if coinciding: a) background formed by blood with minimum or no colloid; b) clusters of epithelial cells with poor cohesion, sometimes multilayered, microfollicular, or stroma-like fusiform cells; c) striking anisocytosis, polygonal, plasmacytoid, fusiform, polyploid, and binucleated cells and naked nuclei in the background; d) striking anisokaryosis, at least part of the nuclei ovoid or elongated, chromatin rough, giant nuclei; e) amyloid identifiable in some tissue micro-fragments. If additional smears or cyto-block material are available it may be possible to establish the diagnosis at the cytology level using amyloid staining, argyrophilia test or immunohistochemistry. However if there is any cytological suspicion of medullary carcinoma, serum calcitonin should be investigated to confirm the preoperative diagnosis of medullary carcinoma enabling the patient to undergo one-step radical surgery. PMID- 8485777 TI - [Use of computer technology in a cytology center for screening of early forms of cervical carcinoma]. AB - Programme setting using an actualized register of inhabitants was described. It has been serving in a cytocentre of the pathology department and for actualization of a district oncological register of patients suffering from cervical carcinoma. PMID- 8485778 TI - [Heterotopic ossification in endobronchial metastases of rectal adenocarcinoma]. AB - An endobronchial metastasis of rectal carcinoma was found in a 62-year-old man three years after removal of the primary tumour. It imitated an aspirated foreign body and produced stromal foci of heterotopic ossification. Focal ossification was noticed in the revised primary tumour as well. PMID- 8485779 TI - [Mycoses of the heart]. AB - There is an increasing frequency of heart mycoses. Authors identified 19 such cases between 1972 and 1991, 63% in the last 6 years (frequency was 0.1% in 17.661 autopsies of patients over 7 days of life). Males prevailed (17:2). Yeasts of genus Candida dominated, unusual etiology represented Candida parapsilosis, Torulopsis candida and Aspergillus restrictus. Sampling from vegetations or abscesses was a prerequisite for positive autoptic cultivation. Probable source of infection was found in 12 patients and 5 of them had an infected thrombosis of venous catheter. Mycosepsis comprised nearly equal number of endocarditides (mostly left sided) and myocarditides. Spread of endocardial infection into myocardium was rare, most myocarditides resulted from disseminated infection in immunocompromised patients. Endocarditides mainly complicated surgical interventions. PMID- 8485780 TI - [Histological structure of the peniform clitoris in congenital adrenogenital syndrome]. AB - Peniform clitoris in 50 girls suffering from congenital adrenogenital syndrome were subtotally removed at the age of 4-6 years and studied by biopsy. A corpus spongiosum more or less developed was found in all cases beneath the corpora cavernosa in the bottom part of corpus clitoridis, epithelial urethral rudiments represented by single or multiple short tubules with transitional epithelium and mucinous glands were found in 46 cases; they were localized in corpus spongiosum or close to it in loose connective tissue. Other urethral rudiments occurring in glans clitoridis were represented by long slight pegs of squamous epithelium extending into corpus spongiosum glandis. Control samples from 20 4-6-year-old girls who had deceased from tumours showed but once heterotopic epithelial urethral rudiments-tubules with transitional epithelium and mucinous glands. PMID- 8485781 TI - Diffuse sclerosing variant of papillary thyroid carcinoma. AB - Five cases of the diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) were presented. The fifth case was discovered in a statistically not defined series of carcinomas of the thyroid gland. DSPC were found in 5.7% of 70 cases of thyroid papillary carcinoma. All the cases described showed a similar histological picture. In the first case a "dominant nodule" was found. Immunohistologically B-cell markers were mostly proved on lymphocytes of the focal lymphocytic infiltration. Accumulation of Langerhans cells was present in the tumour foci. The finding of these cells is regarded as a sign of an enhanced immunological defense mechanism. The clinical follow-up interval of patients was 3 to 9 years. Less favourable prognosis of DSPC as compared with classical papillary carcinomas could not be confirmed in this series. PMID- 8485782 TI - [Carcinoma of the thyroid with the so-called "tall cells"]. AB - Two tall-cell tumours were found in a group of 70 papillary thyroid carcinomas. The tall cells were all over the first tumour whereas in the second case they represented more than 40% of tumour cells. Both patients were followed 8 and 7 years respectively. Cervical lymph node metastases was mentioned in the clinical history of the first case. Biological behaviour of both tumours was not different at large from classical papillary carcinomas. PMID- 8485783 TI - Perturbation of the platelet plasma membrane is not sufficient for inhibition of thrombin-induced PKC-activity. AB - This work was carried out to decide whether a non-specific perturbation of the platelet membrane with exogenous amphiphiles affects protein phosphorylation in platelets, especially phosphorylation mediated by PKC. Effects of amphiphiles per se on protein phosphorylation were also recorded. (i) Sublytic concentrations of the differently charged model surfactants cetyltrimethylammonium bromide (CTAB), Zwittergent 3-16, sodium tetradecyl sulphate, and octaethyleneglycol hexadecyl ether, as well as chlorpromazine, and Triton X-100, did not affect the thrombin induced, PKC-mediated phosphorylation of pleckstrin, whereas sphingosine blocked this phosphorylation. (ii) The sphingosine-mediated phosphorylation blockade is not related to a non-specific perturbation of the membrane, but can instead be attributed to specific properties of sphingosine. (iii) The amphiphiles, per se, had differential effects on protein phosphorylation at sublytic concentrations: a treatment with CTAB, Zwittergent 3-16, and sodium tetradecyl sulphate for 1 min led to phosphorylation of a 49-kDa protein, while treatment with sphingosine for 1 min led to a transient phosphorylation of the myosin light chain as well as a weak phosphorylation of pleckstrin. PMID- 8485784 TI - NO2-induced DNA single strand breaks are inhibited by antioxidative vitamins in V79 cells. AB - Recently, we were able to show that nitrogen dioxide (NO2), a strong oxidant, induced DNA single strand breaks (SSBs) in V79 cells. Possibly, special scavengers, e.g. antioxidative vitamins, may protect cells from NO2-induced damage. Therefore, the effect of various tocopherols, beta-carotene, retinol, and ascorbic acid on NO2-induced SSBs in V79 cells was investigated. Cells were preincubated with vitamins and treated for 10 min with 200 ppm NO2. The rate of SSBs was measured by the alkaline elution assay, the amount of DNA by a fluorimetric assay. Micromolar concentrations of d-gamma-tocopherol inhibited the rate of NO2-induced SSBs by 40%, beta-carotene and ascorbic acid by 25%. None of these vitamins had any effects on DNA or the viability of cells. When incubating the cells with retinol in a medium with pH 8.5, this vitamin inhibited NO2 induced SSBs, reducing them by 35%. However, in high concentrations, retinol itself induced SSBs and influenced cell viability. The results are discussed with regard to many toxic effects of NO2. PMID- 8485785 TI - Differential phospholipid metabolism in rat aortic smooth muscle cells of varying proliferative potential upon long term exposure to phorbol 12-myristate 13 acetate. AB - Subchronic exposure of rats to allylamine (AAM) modulates aortic smooth muscle cells (SMCs) from a quiescent to a proliferative phenotype. This response is associated with alterations in phospholipid metabolism and protein kinase C (PKC) activity. The present studies were conducted to evaluate the effects of long-term exposure to phorbol 12-myristate 13-acetate (PMA) on phospholipid metabolism in SMCs derived from control and AAM-treated animals, cells of varying proliferative potential. Measurements of 32P/[3H]myristic acid incorporation into parent phospholipids and phosphatidic acid (PA) and the extent of PKC-mediated histone phosphorylation were conducted following exposure of pre- and postconfluent subcultures of SMCs to PMA for 3 h. Increased 32P incorporation into phosphatidylcholine (PC) was observed in both pre- and postconfluent cultures of control and AAM cells treated with PMA relative to vehicle. This response was attenuated in pre- and postconfluent AAM cells relative to control counterparts. PMA enhanced 32P incorporation into phosphatidylinositol (PI) in preconfluent cultures of control cells, but decreased 32P incorporation in cultures of AAM cells relative to vehicle. A similar relationship was observed in the PI profile of postconfluent cultures. The alterations in primary phospholipid profiles induced by PMA correlated with the loss of PKC-mediated histone phosphorylation in the cytosolic and particulate fractions of both cell types. The pattern of 32P incorporation into PA, a phospholipid metabolite, paralleled that of PC in cultures of both cell types. In the presence of ethanol, vehicle-treated control and AAM cells exhibited a modest increase in phosphatidylethanol (PEt) formation, as measured by [3H]myristic acid incorporation. PMA enhanced PEt formation in control and AAM cultures, but selectively decreased [3H]myristic acid incorporation into PA in AAM cells. These data demonstrate that long-term PMA treatment differentially modulates phospholipid metabolism in aortic SMCs of varying proliferative potential. These alterations are associated with modulation of PLD-mediated hydrolysis of membrane phospholipids. PMID- 8485786 TI - Mechanism of genotoxicity and electron density distribution by NMR of 5-nitro-3 thiophenecarboxamides, a novel group of direct-acting mutagens in Salmonella typhimurium. AB - The mutagenic activity of 23 5-nitro-3-thiophenecarboxanilides and of 5-nitro-3 thiophenecarboxamide, the prototype, (NTCAs) have been evaluated in the Ames test on Salmonella typhimurium strains TA100 ad TA98 with and without metabolic activation. Effects of different substituents (electron-donating and electron withdrawing) were studied to evaluate structural features that affect the metabolism and the bacterial mutagenic potency. All the derivatives were direct acting mutagens, the mutagenic potency ranging from 0.7 to 142 revertants (rev.)/nmol in TA100 and from 0.09 to 68 rev./nmol in TA98 strain. Results obtained with strains TA98NR and TA98/1,8-DNP6 indicated that the mutagenic activity was largely dependent on bacterial nitroreductase, whereas the O acetylation step was not critical for mutagenic potency. Superoxide (O2-.) and hydroxyl (OH.) scavengers as well as other radical scavengers and enzymes inhibited NTCAs mutagenicity to different extents. In particular, O2-. seemed to be involved in NTCAs mutagenicity, showing a free radical pathway for NTCA metabolism. [1H]- and [13C]NMR data indicated that the effects of different substituents on genotoxicity are probably not exerted on the electron density distribution. The importance of factors such as extent of nitration, reduction potential, orientation of nitrosubstituent and planarity of the molecule are discussed. PMID- 8485787 TI - Monitoring the brain during cardiac surgery in children. PMID- 8485788 TI - Cerebral blood flow velocity patterns during cardiac surgery utilizing profound hypothermia with low-flow cardiopulmonary bypass or circulatory arrest in neonates and infants. AB - To examine the effects of low-flow cardiopulmonary bypass (CPB) and circulatory arrest (PHCA) on cerebral pressure-flow velocity relationships, we studied 32 patients (< 9 mo of age) undergoing corrective cardiac procedures. Pressure-flow velocity relationships were studied during profound hypothermia (nasopharyngeal temperature < 20 degrees C). Cerebral blood-flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler sonography. The anterior fontanel pressure (AFP) was measured using an intracranial pressure monitor. Cerebral perfusion pressure (CPP) was calculated (mmHg) as mean arterial pressure (MAP) minus AFP. Nasopharyngeal temperature, PaCO2 and haematocrit were controlled during the study period. Alpha-stat acid-base management was employed. The CBFV measurements were made continuously over a range of CPP as pump flow (Q) was decreased to low-flow or to circulatory arrest and again during the subsequent increase in Q and CPP to normal. As Q and CPP were increased after a period of low-flow CPB during which period detectable CBFV was present, the CBFV was greater at any given CPP than prior to the low-flow state (P < 0.05). However, after PHCA a higher CPP (P < 0.05) was necessary to re-establish detectable CBFV and at any given CPP the CBFV was less than prior to PHCA (P < 0.05). Seventeen patients underwent low-flow CPB during which CBFV became non detectable (7 +/- 1 cm.sec-1). In 12 of these patients the pattern of recovery of CBFV was the same as that observed after low-flow CPB whereas the remaining five (29%) demonstrated a pattern of recovery identical to the ones recorded after PHCA. We conclude that after PHCA a higher CPP is necessary to re-establish and maintain detectable CBFV. Furthermore, during low-flow CPB, patients where CBFV becomes non-detectable and show a pattern of CBFV recovery similar to PHCA, cessation of cerebral perfusion must be considered. PMID- 8485789 TI - A comparison of epidural tramadol and epidural morphine for postoperative analgesia. AB - The present study compared epidural tramadol with epidural morphine for postoperative analgesia in 20 patients undergoing major abdominal surgery. Intraoperatively, the patients were anaesthetized by a balanced technique of general anaesthesia combined with lumbar epidural lidocaine. In ten of the patients 100 mg tramadol diluted in 10 ml normal saline was also injected epidurally, while 4 mg epidural morphine was used in the other ten patients. In all patients, the visual analogue pain score, PaO2, PaCO2 and respiratory rate were monitored every hour for the first 24 hr postoperatively. In both the tramadol and morphine groups, the mean hourly pain scores ranged from 0.2 +/- 0.6 to 1.4 +/- 2.5 throughout the period of observations. However, the mean PaO2 was decreased postoperatively in the epidural morphine group, while no change was observed in the epidural tramadol group. The maximal decrease of PaO2 in the epidural morphine group was observed at the tenth hour postoperatively, when it decreased to 72.8 +/- 10.3 mmHg. This was not associated with any increase in PaCO2 or a decrease of respiratory rate, suggesting that hypoxaemia rather than hypercarbia or decreased respiratory rate may be an earlier indicator of respiratory rate, suggesting that hypoxaemia rather than hypercarbia or decreased respiratory rate may be an earlier indicator of respiratory depression in patients breathing room air without oxygen supplementation. The absence of clinically relevant respiratory depression following epidural tramadol compared with epidural morphine may be attributed to the different mechanisms of their analgesic action. The results suggest that epidural tramadol can be used to provide prolonged postoperative analgesia without serious side effects. PMID- 8485790 TI - Epidural anaesthesia and analgesia do not affect energy expenditure after major abdominal surgery. AB - Our objective was to determine the effect of perioperative epidural anaesthesia and analgesia on the increase in energy expenditure which accompanies major elective abdominal surgery in a prospective, randomized study. Eight patients undergoing elective resections of the colon and/or rectum received general anaesthesia alone (nitrous oxide, oxygen, and isoflurane, supplemented with intravenous fentanyl to a maximum of 10 micrograms.kg-1), and 12 patients received perioperative epidural anaesthesia and analgesia using lidocaine (carbonated lidocaine 2% with epinephrine 1:200,000, 20 ml over 30 min) and morphine (preservative-free morphine 0.10 mg.kg-1 after catheter insertion and 0.05 to 0.10 mg.kg-1 every 12 hr as needed until the morning following surgery) via a lower lumbar catheter in addition to general anaesthesia. Respiratory gas exchange was measured using a metabolic cart and canopy system early on the morning of surgery, six hours postoperatively, and on the first and second postoperative mornings. Parenteral analgesic administration (P < 0.001) and visual analogue pain scores (P < 0.05) were lower in the patients receiving epidural anaesthesia and time to first parenteral analgesia was longer (P < 0.005). Oxygen consumption, carbon dioxide production, and energy expenditure increased after surgery (all P < 0.001) but were very similar in the two groups (all P > or = 0.8) before and after surgery. Despite substantial effects on postoperative pain, we conclude that oxygen consumption and energy expenditure following major abdominal surgery are not diminished by perioperative epidural anaesthesia and analgesia. PMID- 8485791 TI - Aortocaval compression in the sitting and lateral decubitus positions during extradural catheter placement in the parturient. AB - We prospectively studied the incidence of concealed aortocaval compression in parturients at term during identification of the extradural space. Forty ASA I or II parturients, at term and in active labour, who requested extradural analgesia were randomly allocated to one of two groups. Parturients in the first group (n = 22) were positioned in the left lateral decubitus position and those in the second group (n = 18) were in the sitting position. Cardiac output (CO) was recorded at one-minute intervals for five minutes before extradural catheter placement (supine position with a 15 degrees wedge under the right side), and during and thereafter for five minutes (in the supine wedged position), using the BoMED NCCOM3-R7 thoracic electrical bioimpedance (TEB) monitor. The average of five COTEB recordings before positioning the patient were compared with the average of five COTEB measurements during and after extradural space identification. A change of > 25% COTEB was considered beyond machine variability. Upper limb arterial pressure was recorded at one-minute intervals. In the left lateral decubitus position, 17 of 22 patients demonstrated a > 25% reduction in COTEB compared with five of 18 patients in the sitting position (chi 2, P < 0.01). The percentage change in COTEB in the lateral decubitus position ( 29.8%, 95% CI -17% to -44%) was greater than the sitting position (-9.8%, 95% CI +36% to -32%) (P < 0.01). A decreased incidence of aortocaval compression during identification of the extradural space was demonstrated in the sitting position when compared with the left lateral decubitus position. PMID- 8485792 TI - Perioperative gastric aspiration increases postoperative nausea and vomiting in outpatients. AB - The efficacy of aspiration of gastric contents to reduce postoperative nausea and vomiting was investigated in a controlled randomized, double-blind study of 265 outpatients. Patients in the treated group had their stomachs aspirated with an orogastric tube. In the control group no tube was inserted. Data on the incidence of nausea and vomiting were collected in the recovery room, the day surgery unit and the day after surgery. The overall incidence of postoperative nausea and vomiting was comparable in the two groups. It was also comparable in the recovery room and the day surgery unit. However, treated patients had a higher incidence of both nausea (26.5% vs 12.0%, P < 0.005) and vomiting (16.7% vs 6.8%, P < 0.02) after their discharge from the day surgery unit. We conclude that aspiration of gastric contents with an orogastric tube does not decrease postoperative nausea and vomiting in outpatients and may increase it after discharge of the patient. PMID- 8485793 TI - Nifedipine attenuates the hypertensive response to tracheal intubation in pregnancy-induced hypertension. AB - Thirty women with pregnancy-induced hypertension (PIH) scheduled for Caesarean section under general anaesthesia were studied to evaluate the efficacy of sublingual nifedipine in attenuating the pressor response to laryngoscopy and tracheal intubation. The patients were randomly given either the contents of a nifedipine capsule 10 mg or placebo sublingually 20 min before induction of anaesthesia. Blood pressure and heart rate were recorded at various time intervals. There was a decrease in mean arterial blood pressure (MAP) after pretreatment with nifedipine (P < 0.01). The increase in MAP during laryngoscopy and intubation was higher in the control group compared with nifedipine pretreatment group (P < 0.01). During laryngoscopy and intubation, MAP decreased by 3 mmHg in the nifedipine pretreatment group, while there was an increase of 14 mmHg in the control group. Heart rate increased in both the groups during the laryngoscopy and tracheal intubation (P < 0.01) but the increase was higher in the nifedipine group than in the control group (P < 0.05). Neonatal Apgar scores in both the groups were comparable. These results suggest that sublingual nifedipine is effective in attenuating the hypertensive response to laryngoscopy and intubation but not the tachycardiac response in parturients with PIH. PMID- 8485794 TI - Spinal subdural haematoma in a parturient after attempted epidural anaesthesia. AB - We report a case of spinal subdural haematoma with neurological deficit in a 36 yr-old woman following Caesarean section for severe preeclampsia and placental abruption. She had been taking chronic trifluoperazine treatment for depression. Her activated partial thromboplastin time (aPTT) was 49 sec (normal = 26-36) but all other tests of coagulation were normal. Epidural anaesthesia was attempted but, despite a negative test dose, injection of local anaesthetic resulted in a generalized seizure and general anaesthesia was induced. Seventy-two hours after delivery, she was found to have bilateral leg weakness, urinary incontinence, absent rectal sphincter tone and asymmetrical leg reflexes. The diagnosis of spinal haematoma was confirmed by magnetic resonance imaging. She underwent emergency laminectomy and made a full neurological recovery. PMID- 8485795 TI - The obstetrical anaesthesia assessment clinic: a review of six years experience. AB - We reviewed the out-patient consultation notes of 136 pregnant women seen at the Ottawa Civic Hospital from 1985 to 1991 to evaluate the efficacy of an Obstetric Anaesthesia Assessment Clinic (OAC). In addition, their anaesthetic records from labour and delivery were reviewed. For each patient the reason for referral was recorded according to the involved organ system. The anaesthetic management at delivery was compared with the proposed anaesthetic plan by the OAC consultant (obstetric anaesthetist). The majority of women 84 (62%) had complaints related to the musculo-skeletal system. In addition, 18 patients were referred because of previous anaesthetic problems, ten with a history of cardiac disease, and eight with neurological disease. Lumbar epidural analgesia (LEA) was a safe and effective choice for parturients with low back pain, history of lumbar fractures or single level discectomies without lumbar fusion. Parturients with posterior instrumentation experienced an increased incidence of inadequate pain relief from LEA. Individualized anaesthetic management plans were executed for parturients with spina bifida occulta, neurological, cardiac, and haematological disease as well as for women, with a history of adverse drug reactions and previous problems with regional or general anaesthesia. It is concluded that the OAC has provided a valuable service to obstetricians and anaesthetists for the anaesthetic management of pregnant women with co-existing disease. The OAC gave an opportunity for patient education regarding anaesthetic options for labour and delivery. The attending anaesthetist was provided with a risk assessment and anaesthetic management plan which was adhered to with only two exceptions. Finally, the obstetrician was given consistent advice regarding anaesthesia management that may affect obstetrical decisions. PMID- 8485796 TI - The laryngeal mask airway and prolonged balanced regional anaesthesia. AB - The purpose of this paper is to report an eight-hour operation in which anaesthesia was provided by a combination of continuous epidural analgesia and light general anaesthesia administered via a laryngeal mask. During the perioperative period, the respiratory system was monitored with arterial blood gas and thoraco-abdominal movement analyses. There was no deterioration in respiratory function nor evidence of respiratory fatigue. We suggest that this is a suitable technique in fasting healthy patients undergoing prolonged surgery to the extremities. PMID- 8485797 TI - Harold Griffith Memorial Lecture. The Griffith legacy. AB - 1992 was the anniversary of Crawford Long's use of ether in 1842, and Griffith and Johnson's introduction of Intocostrin into anaesthetic practice in 1942. Harold Randall Griffith was born in Montreal in 1894 and died in 1985. He interrupted his medical studies to serve in the first world war and was awarded the Military Medal for gallantry at the battle of Vimy Ridge. Griffith qualified from McGill University in 1922. After spending a year studying homoeopathic medicine, he joined his father's general practice and became the anaesthetist to the Homoeopathic Hospital in Montreal. He succeeded his father as Medical Director of the hospital (now renamed the Queen Elizabeth Hospital) in 1936 and retired in 1966. Griffith was a superb clinical anaesthetist. He was an early advocate of detailed anaesthetic records, and was responsible for the introduction of both ethylene and cyclopropane into Canadian practice, later teaching himself to intubate under these two agents. Griffith was one of the first to be concerned with standards of patient care. He introduced postoperative recovery and intensive care units into Canadian practice and played a major role in postgraduate teaching. He was unstinting in his support of organisations designed to further the progress of anaesthesia and was the first President of the Canadian Anaesthetist's Society. He was one of those responsible for inaugurating the World Federation of Societies of Anaesthesiology and was President of the First World Congress of Anaesthesiology in 1955. It is remarkable that the introduction of curare into anaesthetic practice was delayed until 1942, since curare had been used in anaesthesia some 30 years previously. However, it was probably Griffith's confidence in his own clinical abilities which enabled him to seize the opportunity when it was offered. PMID- 8485798 TI - Liquid crystal skin thermometry: an accurate reflection of core temperature? AB - Oesophageal, rectal, bladder, tympanic and pulmonary artery sites are used intraoperatively to measure body temperature. However, the temperatures measured at each site have different physiological and practical importance. The present two-part study sought to compare liquid crystal (CR) skin temperature with other temperature monitors which are used routinely during surgery. The first part compared CR with oesophageal (OS) temperature during general inhalational anaesthesia. The second part compared CR with OS, pulmonary artery (PA), and bladder (BL) temperatures during the periods of rapid temperature change associated with cardiopulmonary bypass (CPB). During the first part, the mean difference between OS and CR was -0.14 +/- 0.85 degrees C; this difference remained consistent over time (P < 0.05 by repeated measures analysis of variance). During the second part, the difference in temperature readings between CR and each of the other monitors remained consistent except for CR vs PA and CR vs OS during the cooling period of CPB, when the iced cardioplegia slush directly affected the PA and OS temperatures. This study suggests that CR, an inexpensive and noninvasive means of temperature monitoring, reflects trends in temperature changes in the clinical setting. PMID- 8485799 TI - Delivery of constant air-oxygen mixtures using a closed circle absorber system. AB - The aim of this study was to devise and validate a technique to deliver constant air-oxygen mixtures from a standard anaesthetic machine using only oxygen as the compressed gas source. The common gas outlet was modified to allow measured quantities of ambient air to be insufflated via a three-way attachment into a closed circle absorber system with a double-circuit collapsible bellows ventilator. During positive pressure ventilation, leakages of between 50-150 ml.min-1 occur from the circuit and nomograms of the minimal air and oxygen flow rates needed to maintain constant oxygen concentrations in the presence of the leaks were then mathematically derived. The accuracy of the nomograms was tested on three different anaesthetic machines using test lung models. There were no differences observed among the mean oxygen concentrations using the three machines. Pooled mean values (SD) of 30.65% (0.77), 51.07% (1.04) and 70.4% (0.73) were obtained for predicted inspired concentrations of 30, 50 and 70% respectively. Next, the technique was studied on 18 patients who underwent isoflurane or propofol anaesthesia (duration 40-210 min) for various surgical procedures. Pooled mean values (SD) obtained were 29.3% (1.86), 40.95% (1.65) and 50.06% (1.41) respectively for predicted oxygen concentrations of 30, 40 and 50% respectively. We conclude that this technique can be used to deliver constant air oxygen mixtures accurately during inhalational or total intravenous anaesthesia when N2O is contraindicated but a source of compressed air is not readily available. PMID- 8485800 TI - Assessment of the arterial tonometer (N-CAT) for the continuous blood pressure measurement in rapid atrial fibrillation. AB - The N-CAT is a newly developed arterial tonometer (TBP) able to determine systolic, diastolic and mean arterial blood pressures continuously and noninvasively. The aim of this study was to evaluate the accuracy and reliability of TBP relative to directly measured invasive blood pressure (IBP) in ten haemodynamically stable postoperative cardiac patients who were in rapid atrial fibrillation (HR > or = 100 bpm). There were differences between TBP and IBP for systolic (-1.7 mmHg) and diastolic (+0.9 mmHg) values but not for the mean arterial blood pressures. The N-CAT was able to follow blood pressure changes closely and demonstrated an average systolic, diastolic and mean bias (+/-SD) of 1.71 +/- 4.6, 0.99 +/- 4.6 and 0.33 +/- 4.2 mmHg, respectively. Although these biases are within the required standards for equivalency for noninvasive blood pressure to invasively determined blood pressure, approximately 20% of the readings were > +/- 10 mmHg while only 5% were > +/- 20 mmHg. Moreover, there were occasional discrepancies of sufficient magnitude and duration which may limit the clinical usefulness of the N-CAT in patients in whom continuous and accurate blood pressure measurement is required. PMID- 8485801 TI - LMA and respiratory arrest after anterior cervical fusion. PMID- 8485802 TI - Rubber and plastic endotracheal tube cuffs are highly vulnerable to the CO2 laser. PMID- 8485803 TI - Exposure to N2O. PMID- 8485804 TI - Portex epidural catheters. PMID- 8485805 TI - Identification of serum components that inhibit the tumoricidal activity of amphiphilic alpha helical peptides. AB - Antimicrobial peptides that can form amphiphilic alpha helices were tested for their ability to lyse various human tumor cell lines in vitro. These peptides include C18G, whose sequence is a derivative of the carboxyl terminus of human platelet factor IV, and 399, an idealized amphiphilic alpha helix. Both peptides exhibited potent antitumor activity against all cell lines tested, unlike magainin 2, a naturally occurring antimicrobial peptide of similar structure, which was relatively inactive under the same conditions. Also, the lytic activity of C18G is specific for tumor cells versus human red blood cells. The effects of serum can be important when evaluating the potency of lytic peptides, since other tumoricidal peptides have been shown to be completely inactivated by low serum levels. Experiments with C18G and 399 revealed that their activity was indeed reduced in the presence of human serum, but that significant lytic activity remained even at relatively high serum concentrations. Various serum components were tested for their inhibitory activity. Whereas albumin and high-density lipoprotein had only slight inhibitory properties, low-density lipoprotein was found to be a potent inhibitor of peptide-mediated cell lysis. The peptide 399, which is more sensitive to serum inhibition than C18G, also binds more extensively to all serum components tested. PMID- 8485806 TI - The antitumor activity of the platinum complex D-17872 is associated with tumor cell differentiation. AB - The novel cisplatin analogue D-17872 was studied for its anticancer activity using in vivo and in vitro preclinical models. The compound at the sublethal dose of 215 mg/kg (ca. 50% of the approximate LD50) induced no nephrotoxic effect strong enough to increase the blood urea level in rats. It had good in vivo antitumor efficacy against murine P388 (max. ILS: D-17872 132%, cisplatin 55%) and L1210 leukemia (max. ILS: D-17872 43%, cisplatin 38%), L5222 leukemia of the rat (max. ILS: D-17872 163%, cisplatin 163%) and murine B16 melanoma. Activity against P388 leukemia substantially exceeded that of cisplatin. Moreover, the M5076 reticulum cell sarcoma implanted into the subrenal capsule and the DMBA induced mammary tumor of the rat were inhibited by D-17872 to a greater extent than by cisplatin (min. T/C: D-17872 -3%, cisplatin 11%). Using clonogenic microassays, D-17872 was active in vitro against a variety of human and rodent tumor cell lines, albeit at higher concentrations than cisplatin (IC50 values: D 17872 2.6-12.7 mumol/l, cisplatin 0.13-0.42 mumol/l). Apart from its cytotoxic action it was able to induce in vitro differentiation of the human HL-60 and K562 and of the murine M1-T22 cell lines, while cisplatin induced differentiation only in the HL-60 cell line. Thus D-17872 exhibited a pharmacological and toxicological profile different from that of the parent compound. The results suggest that induction of differentiation contributes to the antineoplastic efficacy of this novel cisplatin derivative. PMID- 8485807 TI - L-asparaginase kills lymphoma cells by apoptosis. AB - Microscopic examination of histological sections of lymph nodes from a canine case of malignant lymphoma at 4 h after treatment with L-asparaginase revealed massive destruction of neoplastic cells by what was consistent with apoptosis morphologically. Apoptosis as the mode of cell death after asparaginase treatment was confirmed in a mouse lymphoma cell line (LY-TH) by the characteristic fragmentation of DNA into oligonucleosome-sized pieces and by the morphological changes consistent with apoptosis following treatment in vitro. Applied to these cells, asparaginase was found to be most cytotoxic over the range of 1-10 IU/ml. Even after 4 h of asparaginase treatment at 100 IU/ml, protein synthesis was reduced by only one-half, yet DNA fragmentation reached 40%. Other agents that affect protein synthesis (cycloheximide and actinomycin D) caused apoptosis as well; however, agents (radiation, prednisolone, and VP-16) whose mechanisms are different from inhibition of protein synthesis also caused apoptosis. As such, it seems unlikely that protein depletion per se and/or the elimination of specific short-lived proteins is the triggering event that leads to cell death. It is more likely that the suspension of cellular proliferation commits cells to apoptosis after asparaginase treatment. PMID- 8485808 TI - Gas-chromatographic analysis of busulfan for therapeutic drug monitoring. AB - The development and validation of a gas chromatographic assay method for determination of total and free busulfan concentrations in human plasma for pharmacokinetic studies is reported. 1,6-Bis(methanesulfonyloxy)hexane, the internal standard, and a potential metabolite, 3-hydroxysulfolane, were synthesized. Plasma and plasma ultrafiltrate samples containing busulfan and internal standard were extracted with ethyl acetate and derivatized with 2,3,5,6 tetrafluorothiophenol prior to gas chromatographic determination. The 63Ni electron-capture detector provided a limit of detection of 0.0600 microgram/ml with a limit of quantitation of 0.100 microgram/ml busulfan in biological samples. Calibration curves were linear from 0.100 to 3.00 micrograms/ml in plasma (500 microliters) and 0.100 to 2.00 micrograms/ml in plasma ultrafiltrate (100 microliters). Extraction and derivatization yields ranged from 78.4% to 89.6% and 56.0% to 71.3%, respectively. Specificity of this assay for busulfan in the presence of its potential metabolites was demonstrated. Also, plasma samples containing co-administered drugs gave no response under these conditions. Clinical samples obtained following administration of a 1 mg/kg oral busulfan dose demonstrate the applicability of this method to analysis of total and free plasma concentrations. PMID- 8485809 TI - Disposition and metabolism of KW-2149, a novel anticancer agent. AB - KW-2149 is a new derivative of mitomycin C (MMC). The plasma concentrations, distribution, metabolism, and excretion of [3H]-KW-2149 in normal and tumor bearing mice after i.v. administration of 16.6 mg/kg were investigated. The plasma radioactivity decreased biexponentially after i.v. administration in normal mice. However, the unchanged drug disappeared rapidly, showing a half-life (t1/2) of 9.7 min, which was shorter than MMC's (18 min). The radioactivity was excreted in mouse urine (33%) and feces (58%) within 144 h. High radioactivity was distributed in the gallbladder, liver, kidney, pancreas, and lung at 1 h after i.v. administration to normal mice. The tumor concentration was lower than the plasma or blood concentration. The lowest radioactivity was observed in the brain. The metabolic rate of KW-2149 was very rapid. The methyl sulfide form (M 16), the symmetrical disulfide dimer (M-18), and the albumin conjugate were detected in plasma, which possessed anticellular activity. The specific anticellular activity of these compounds against uterine carcinoma (HeLa S3) was 1/100, 1, and 1/20 respectively, as compared with that of KW-2149. PMID- 8485810 TI - The comparative disposition of the pyrolloquinone GR63178A and its 9-hydroxy metabolite GR54374X in sensitive and resistant mouse colon adenocarcinoma. AB - The novel anticancer compound GR63178A is being evaluated in the clinic, having demonstrated activity against a wide range of experimental tumour systems in animals without significant toxic side-effects being apparent. In this work, we have demonstrated significant antitumour action of this compound against one murine colon cancer model (colon 38 tumour in BDF-1 mice, specific growth delay = 1.2) when given at 10 mg/kg over 21 consecutive days and in contrast shown minimal sensitivity of another similar murine colon adenocarcinoma, MAC 26, in NMRI mice with the same dose regime. We investigated the disposition of both the parent drug and the 9-OH metabolite (GR54374X) in plasma, tissues and tumours, using solid phase extraction followed by reversed-phase high performance liquid chromatography. Although plasma clearance profiles of GR63178A were similar, significant differences were seen in the disposition of the drug to major organs in two mouse strains. Noteably, the liver and kidneys of the sensitive model had higher levels of parent drug and 9-OH metabolite at both 30 min and 4 h post injection. However, this was not apparent in the tumours themselves, and the levels of 9-OH metabolite were lower in the plasma and higher in the urine of the sensitive mice, indicating possible rapid renal clearance of this compound. Neither GR63178A nor GR54374X proved cytotoxic in in vitro experiments. The data presented here have revealed considerable variation in drug handling by these two mouse strains, but this did not produce different levels of either parent drug or GR54374X in the tumours, which are the presumed targets, suggesting that differences in disposition are probably not responsible for the different sensitivities of the two tumours. Other possible explanations include the production of a hitherto undetected ultimate cytotoxic metabolite in the sensitive, but not in the resistant, mouse/tumour combination, or differences in inherent tumour sensitivity, or in host-mediated effects. These possibilities are discussed. PMID- 8485811 TI - New drug design and development in cancer: present status and future perspectives. PMID- 8485812 TI - Role of DNA repair in the mechanisms of cell resistance to alkylating agents and cisplatin. PMID- 8485813 TI - Alkylphosphocholines: a new class of membrane-active anticancer agents. PMID- 8485814 TI - Use of pharmacokinetic-pharmacodynamic relationships in the development of new anthracyclines. PMID- 8485815 TI - Granulocytes of critically ill patients spontaneously express the 72 kD heat shock protein. AB - Polymorphonuclear neutrophils (PMN), through their ability to release oxygen-free radicals and other tissue-damaging molecules, play a major role in the pathogenesis of multiple organ failure syndrome (MOFS). There is evidence that heat shock proteins (stress proteins; HSPs) are involved in cellular repair mechanisms, and are protecting cells against oxidative injury. In this study, we analyzed the spontaneous expression of the 72 kD HSP (HSP72) in peripheral blood PMN of 20 critically ill patients (16 polytrauma victims, four patients after major surgery) admitted to an intensive care unit. The expression of HSP72 was investigated in PMN of patients and healthy donors by immunohistochemistry. We found spontaneous expression of HSP72 in PMN of 12 (60%) of 20 patients. No specific staining was detected in PMN of healthy donors (n = 10). In PMN of six of 12 patients expressing HSP72 without previous heat treatment, we found an impairment of respiratory burst activity (RBA) compared to the control population. These results demonstrate for the first time the in vivo expression of HSP72 in human leukocytes without previous heat treatment, and suggest a possible role of this protein in patients suffering from severe tissue injury. PMID- 8485816 TI - Vasodilating prostaglandin E1 decreases critical oxygen delivery by increasing critical oxygen extraction in anesthetized pigs. AB - The abnormal dependence of O2 uptake (VO2) on O2 delivery (QO2) during severe sepsis, and the adult respiratory distress syndrome (ARDS) may be caused by impaired vascular reactivity, following release of vasodilating prostaglandins. Infusion of these compounds, however, may improve tissue oxygenation. We studied the effect of vasodilating prostaglandin E1 (PGE1; 0.2 microgram/kg/min) on the critical O2 extraction ratio (ERO2c) and the critical QO2 (QO2c) in a saline controlled, crossover study in 12 barbiturate-anesthetized pigs. QO2, VO2 (independently from QO2), and blood lactate concentrations were measured during graded cardiac output reductions by incremental positive end-expiratory pressure (0-20 cm H2O PEEP, raised by 5 cm H2O at 15 min intervals). At 0 cm H2O PEEP, PGE1 decreased arterial blood pressure, mainly due to a fall in systemic vascular resistance. From 0 to 20 cm H2O PEEP, the fall in QO2 was greater in the PGE1 than in the saline series (P < 0.005), since ventricular filling and the rise in heart rate were less in the former. The decrease in VO2 (P < 0.005) did not differ between series. As estimated from bilinear regression on paired VO2/QO2 data in individual pigs, the QO2c was 9.8 +/- 3.6 (mean +/- SD) during PGE1 and 14.6 +/- 3.8 ml/kg/min during saline infusion (P = 0.008), with ERO2c 68% +/- 16% and 48% +/- 12%, respectively (P < 0.005). The QO2c, estimated from bilinear regression on paired lactate/QO2 data during the first treatment period, was 7.1 +/- 1.2 for PGE1 and 12.8 +/- 4.5 ml/kg/min for saline (P < 0.05), at similar lactate concentrations (2.0 +/- 0.5 and 1.7 +/- 0.5 mmol/liter, respectively). PGE1-induced vasodilation thus decreases QO2c, because of increased ERO2c, probably resulting from capillary recruitment, an increased surface area available for O2 exchange, and decreased O2 diffusion distances. Hence, a reduced ERO2 and abnormal supply dependence of VO2 during severe sepsis and ARDS are not caused by release of vasodilating prostaglandins. In contrast, our results partly explain improved tissue oxygenation with these compounds during abnormal VO2 supply dependence, following sepsis and ARDS. PMID- 8485817 TI - Gut bacterial translocation/dissemination explains the increased mortality produced by parenteral nutrition following methotrexate. AB - Mortality is reported to be higher in methotrexate (MTX)-treated animals receiving total parenteral nutrition (TPN), compared to animals receiving enteral nutrition. The increased mortality is felt to be related to gut atrophy and bacterial translocation. In this study, we examined the effect of MTX (30 mg/kg) on survival, body weight loss, gut mass, and gut bacterial translocation in rats randomized to TPN or enteral nutrition. Twenty-four male Sprague-Dawley rats (n = 8 per group) were randomized to TPN, a peptide-based enteral diet (PEP), or CHOW. Animals were weighed daily and followed for survival (6 days). A separate group of rats (n = 6 per group) were similarly randomized and sacrificed at 3 days. Mesenteric lymph node complex, liver, spleen, lung, and blood were cultured for translocating bacteria. Body weight loss was similar in all groups (12.0-16.9 g/day). Mortality was significantly (P < 0.05) higher in the TPN animals (100%), compared to PEP (50%) and CHOW (25%) fed animals. All tissues in the TPN animals contained large quantities of bacteria, while most tissues in the CHOW group were free of bacteria. Bacterial counts in the PEP tissues were intermediate between TPN and CHOW. There were no significant differences between groups for gut weights or mucosal protein content. This study supports a direct relationship between bacterial translocation and mortality in rats following MTX. PMID- 8485818 TI - Relative contribution of renal nerve and adrenal gland to renal vascular tone during prolonged canine hemorrhagic hypotension. AB - This study was designed to determine roles of renal sympathetic nerve activity (RNA) and adrenal catecholamines in the changes of renal vascular resistance during prolonged hemorrhagic shock in anesthetized dogs. In animals with intact baroreceptors, hemorrhagic hypotension (40 mm Hg) caused RNA to increase significantly within 1 min after bleeding, followed by a return to baseline within 10 min. Thereafter, a secondary increase in RNA occurred that was followed by a gradual decline towards the baseline level. The renal perfusion pressure (RPP) showed a progressive and significant increase until the end of the experiment. The initial increase in RNA was abolished by complete denervation of the systemic baroreceptors. The initial increase in RPP, which was observed within 10 min after bleeding in animals with intact baroreceptors, was attenuated by the denervation. In animals with bilateral adrenalectomy, RPP still showed an initial increase, but the progressive increase throughout the entire experimental period did not occur. In animals with baroreceptor denervation and bilateral adrenalectomy, RPP did not show any significant changes during the experiment. These results indicate that the initial renal vasoconstrictive response to hemorrhage is regulated by a reflex sympathetic mechanism. In contrast, a late renal vasoconstriction during hemorrhagic hypotension is predominantly evoked by humoral substances such as adrenal catecholamines. PMID- 8485819 TI - Tumor necrosis factor depresses gut absorptive function. AB - Although recent studies have shown that gut absorptive function is significantly depressed even in the early hyperdynamic phase of sepsis, the mechanism responsible for this is unknown. Tumor necrosis factor (TNF-alpha) is a potent mediator of shock resulting in a marked inflammatory response leading to mucosal erosions of the gut and multiple organ failure. Although TNF is elevated in early sepsis, it remains unknown whether TNF plays any role in the depression of gut absorptive function under these conditions. To study this, we used the 1 hr D xylose absorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery from anesthesia, 125 micrograms recombinant murine TNF-alpha (rMuTNF-alpha)/kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hour later, D-xylose was given orally. The systemic blood pressure was recorded 1 hr thereafter and D xylose concentration in a sample of portal blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-alpha, D-xylose absorption was severely depressed. Thus the depressed gut absorptive function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-alpha. PMID- 8485820 TI - Analysis of endotoxin effects on pulmonary circulation in terms of pressure-flow characteristics. AB - The purpose of the present work was to explore the hypothesis that pulmonary vasoconstriction secondary to endotoxin insult results mainly from an increase in the critical closing pressure of the pulmonary vessels. Specifically, we reasoned that in the face of a Starling resistor located between pulmonary arteries and left atrium, upstream transmission of increased left atrial pressure (Pla) would be inversely related to the level of the pressure intercept (Pi) obtained by extrapolation from the linear pulmonary arterial pressure (Ppa)--flow (Q degrees) plot. Six dogs (group E) were infused with Escherichia coli endotoxin (0.25 microgram/kg/min) for 2 hr, whereas six additional dogs (group C) served as control. During baseline conditions, Pi approximated LAP in both groups. In group C dogs, increasing LAP at constant Q degrees led to a proportional augmentation of Ppa. In group E dogs, endotoxin resulted in a shift of the Ppa-Q relationships to higher pressures due to both increases in Pi and slope. In addition, changes in Pla over the same range as in control dogs affected Ppa only at the highest levels of Pla. We conclude that endotoxin insult increases the critical closing pressure that exceeds Pla and induces the occurrence of a Starling resistor responsible for the production of an effective vascular waterfall. PMID- 8485821 TI - Potentiation of decreased pyruvate dehydrogenase activity by inflammatory stimuli in sepsis. AB - The effect of inflammation and chronic sepsis on the activity of pyruvate dehydrogenase complex (PDH) in skeletal muscle was investigated in rats. Inflammation was induced by the placement of a catheter in the carotid artery. Sepsis was induced by repeated (every 48 hr) injections of an inoculum composed of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Hindlimb muscle was sampled 7 or 14 days following the initial injection of the inoculum into the abscess. Total PHD activity was not altered by any of the conditions examined. There were no differences in the proportion of active PDH complex after 7 days in any of the conditions examined. In contrast, 14 days after the initial bacterial injection, the concentration of active PDH complex in skeletal muscle was reduced by 50% in the septic rats. The combination of intravascular catheterization and infection resulted in a further decrease in the concentration of active PDH complex. The decreased concentration of active PDH complex was associated with increased plasma lactate concentrations in septic rats. Catheterization exacerbated the rise in plasma lactate in sepsis. In this model of chronic sepsis, the magnitude of the hyperlactatemia and the inhibition of the PDH complex in skeletal muscle appear dependent upon the length of time of the septic insult and are potentiated by addition of an intravascular focus of inflammation. PMID- 8485822 TI - Effects of pentoxifylline on tumor necrosis factor production and survival during lethal E. coli sepsis vs. disseminated candidiasis with fungal septic shock. AB - Lethal circulatory shock during microbial sepsis is thought to be initiated by early molecular events, including production of tumor necrosis factor (TNF) and cytokine-mediated upregulation of neutrophil (PMN) function, irrespective of the causative organism. The phosphodiesterase inhibitor pentoxifylline (PTX) inhibits TNF gene transcription and modulates PMN function, and has been shown to improve outcome in experimental sepsis. We hypothesized that PTX would attenuate gram negative and fungal septic shock by different mechanisms: reduced TNF production in Escherichia coli (EC) sepsis vs. enhanced PMN-mediated defense during Candida albicans (CA) fungemia. Conscious chronically catheterized rats received PTX (25 mg/kg, i.v.) before i.v. challenge with 10(10) viable EC (serotype 055:B5), 10(9) viable serotype A yeast-phase CA (each the LD100 in < 24 hr in naive rats), or normal sterile saline (NSS), and then PTX posttreatment (6.5 mg/hr x 4.5 hr). Treatment controls received NSS before and after challenge. Serum TNF peaked 1.5 hr after EC infection in NSS-treated animals (1654 +/- 390 U/ml, mean +/- SE), and was significantly reduced by PTX (120 +/- 32 U/ml, P < 0.01), but PTX did not improve 24 hr survival. PTX also aggravated systemic hypotension after EC, and did not modify neutropenia, thrombocytopenia, or microvascular permeability assessed by organ wet/dry weight (W/D) ratios. Peak serum TNF in CA + NSS animals (130 +/- 45 U/ml) was delayed 8 hr compared to EC animals, and were not reduced by PTX (67 +/- 25 U/ml, P = NS). Moreover, PTX did not alter CA-induced mortality, hypothermia, hypotension, neutropenia, increased lung W/D, or interstitial and alveolar hemorrhage. We conclude that PTX-induced suppression of endogenous TNF production does not prevent gram-negative shock in this model, possibly due to impaired TNF-mediated antibacterial host defense. Since fungal septic shock with acute disseminated candidiasis evolves prior to significant increases in circulating TNF, PTX also appears ineffective in its treatment. PMID- 8485823 TI - Responses to trauma: fifty years of ebb and flow. PMID- 8485824 TI - Development, early treatment, and prevention of heart failure. Introduction. PMID- 8485825 TI - Improvement of cardiac function by angiotensin converting enzyme inhibition. Sites of action. AB - BACKGROUND: The discovery of new properties of angiotensin converting enzyme (ACE) inhibitors in addition to their well-known ability to lower blood-pressure, such as antiproliferative actions and antiadrenergic and vagal-stimulating effects, has contributed to the usefulness of this class of agents in the prevention and treatment of cardiovascular diseases. METHODS AND RESULTS: The contribution of an activated endocrine and/or cardiac paracrine renin-angiotensin system to the progression of cardiovascular diseases with the exception of renovascular hypertension is not fully understood. In particular, the following questions were addressed: 1) Is the facilitation of noradrenaline release in the genesis of arrhythmias a target for ACE inhibition? 2) Is an impaired nutritional cardiac blood flow in heart failure a target for ACE inhibition? 3) Is the intimal hyperplasia that results from coronary angioplasty a target for ACE inhibition? 4) Is the diastolic dysfunction associated with left ventricular hypertrophy in essential hypertension a target for ACE inhibition? In an isolated rat heart preparation with ischemia-induced arrhythmias, none of the ACE inhibitors nor an angiotensin II antagonist was able to significantly suppress the incidence or severity of arrhythmias. In 12 patients with New York Heart Association functional class II-IV heart failure, a fall in cardiac filing pressures after ACE inhibition was associated with an immediate rise in cardiac output and an increase in coronary blood flow of almost 30%. In 24 patients with angina at rest, a preceding percutaneous transluminal coronary angioplasty, and a second angioplasty, control angiograms at 6 months revealed a high degree of restenosis in both ACE inhibitor-treated and placebo patients. Luminal narrowing amounted to 72% in the placebo group and 61% in the ACE inhibitor group. The differences between placebo and enalapril were statistically not significant. In 12 patients with essential hypertension treated with 5 mg cilazapril, left ventricular mass was reduced by 30%, which was closely related to the change in mean arterial blood pressure. The concomitant normalization of the diastolic filling pattern by ACE inhibition, however, was not related to the respective changes in blood pressure. CONCLUSIONS: Promising experimental data regarding the antiproliferative effects of ACE inhibitors in preventing restenosis could not be transferred into clinical benefits for patients who underwent repeat coronary angioplasty. Possible antiarrhythmic effects of ACE inhibitors are not likely to be caused by their suppression of noradrenaline release during myocardial ischemia. ACE inhibition was effective in reducing coronary resistance in patients with severe heart failure, thereby augmenting nutritional cardiac blood flow. ACE inhibition also effectively induced a regression of left ventricular hypertrophy in essential hypertension. The associated normalization of diastolic filling pattern may represent an important goal in the treatment of hypertension. PMID- 8485826 TI - ACE inhibitors in early stages of heart failure. AB - BACKGROUND: Chronic blockade of the renin-angiotensin system by angiotensin converting enzyme (ACE) inhibitors in patients with mild to moderate heart failure as a second-line therapy has been shown to exert beneficial effects on exercise tolerance and symptomatology. METHODS AND RESULTS: Studies in experimental heart failure have shown that early inhibition of the renin angiotensin-aldosterone system leads to a retardation in the progression of cardiac failure and improves survival. Recently, published data from large controlled trials also indicate that ACE inhibitors prolong survival in patients with mild and moderate heart failure. The beneficial effects of ACE inhibition, even in early phases of the genesis of heart failure, are mainly due to a reduction of the progression of pump failure, whereas the incidence of sudden cardiac death remains unchanged. CONCLUSIONS: It can be concluded from these data that ACE inhibitors are no longer an add-on therapy in patients with mild to moderate heart failure but are clearly indicated for the treatment of symptomatic patients with mild heart failure as a first-line therapy. PMID- 8485827 TI - Development and prevention of congestive heart failure following myocardial infarction. AB - Ischemic heart disease is the major etiology for the development of congestive heart failure. Patients with acute myocardial infarction have a greatly increased risk for mortality and for manifesting symptomatic heart failure. This risk is not a uniform one but is greatly augmented in patients with a more extensive infarction and, consequently, a more depressed global ventricular function. An important concept that was derived from studies in rats with myocardial infarction and has been confirmed in patients is that ventricular enlargement, which has been shown to be a marker for an adverse outcome, can be a progressive process that leads to further deterioration of ventricular performance. Both experimental and early clinical studies have indicated that chronic therapy with an angiotensin converting enzyme inhibitor may attenuate this progressive ventricular enlargement. More definitive clinical trials are currently under way to determine whether this form of therapy, which may diminish the extent of ventricular enlargement over time, will result in an improvement in survival and in the prevention of the development of congestive heart failure. The addition of this pharmacological therapy to that of the primary prevention of atherosclerosis and that of the limitation of infarct size should make a substantial impact on the reduction of the incidence of congestive heart failure. PMID- 8485828 TI - Reduction in mortality by pharmacological therapy in congestive heart failure. AB - Mortality in congestive heart failure remains high. In analysis of heart failure in the perspective of pathophysiological mechanisms, some approaches to treatment to improve survival become particularly interesting. The concept of unloading myocardial performance by reducing systemic vascular resistance has received general acceptance. This approach was associated with improved survival with nitrates and hydralazine in the V-HeFT I study. Stimulation of the myocardium in excess of what is achieved by endogenous stimulation might be dangerous. Long term therapy with positive inotropic agents, therefore, is not an appropriate approach at present. However, addition of beta-blockers may protect the myocardium from the intense endogenous sympathetic stimulation in congestive heart failure. There are favorable trends with this approach in several small trials. An ongoing trial in idiopathic dilated cardiomyopathy may help to clarify this question. Counteraction of neuroendocrine activation may also be obtained by the addition of an angiotensin converting enzyme inhibitor. The CONSENSUS I study demonstrated a clear improvement in survival among very compromised patients by addition of enalapril. A positive effect was significantly associated with the degree of neuroendocrine activation at baseline. Two recent large-scale trials have emphasized the importance of adding an angiotensin converting enzyme inhibitor to other treatments in patients with mild to moderate symptoms and left ventricular dysfunction. These trials also support the importance of myocardial protection from neuroendocrine stimulation with symptomatic or asymptomatic myocardial failure. Antiarrhythmic agents have not been documented to improve survival. On the contrary, class I agents are deleterious in some patients with left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485829 TI - Cardiac mechanics during development of heart failure. SOLVD Investigators. AB - BACKGROUND: The changes in myocardial performance responsible for the progression from a stage of asymptomatic left ventricular dysfunction toward overt congestive heart failure are still poorly understood. Accordingly, using invasive methods, we examined the differences in baseline left ventricular function between a subgroup of patients enrolled in the treatment arm (presence of congestive heart failure) and in the prevention arm (asymptomatic patients) of the Studies of Left Ventricular Dysfunction. METHODS AND RESULTS: High-fidelity left ventricular pressures and frame-by-frame angiographic volumes were simultaneously obtained under baseline conditions in 65 patients with left ventricular ejection fraction < or = 35%. Sixteen patients had New York Heart Association congestive heart failure (class II or III), whereas the remaining 49 patients had no clinical signs of heart failure and did not receive therapy for this syndrome. A second set of data was obtained an average of 12.4 months later in 42 patients. The group with heart failure had significantly greater end-diastolic and end-systolic volumes than the asymptomatic group (both p < 0.001), but the stroke index at rest was similar in both groups. Accordingly, ejection fraction was significantly lower in the heart failure group (19.6 +/- 7.0% versus 26.3 +/- 7.2%; p < 0.02). Left ventricular end-diastolic pressure was greater and peak +dP/dt was lower in heart failure patients, but the difference did not reach statistical significance after Bonferroni correction for multiple comparisons. Moreover, the individual end-systolic stress/end-systolic volume data of the heart failure patients fell within the 95% confidence interval of the relation observed in the patients without heart failure both at baseline and after 1 year of follow-up irrespective of their changes in functional status. It was also noted that during follow-up, the changes in end-diastolic and end-systolic volumes correlated linearly, as if both dimensions always shifted in parallel, whereas alterations in contractility primarily influence end-systolic volume. CONCLUSIONS: These observations are compatible with the hypothesis that a depression in the mechanical performance of the viable myocardial areas is not the major determinant for the progression from asymptomatic to symptomatic left ventricular dysfunction. Abnormalities in left ventricular diastolic distensibility, on the other hand, might underlie the progressive ventricular dilation and create a vicious cycle through the afterload mismatch. PMID- 8485830 TI - Cardiac hypertrophy and failure--a disease of adaptation. Modifications in membrane proteins provide a molecular basis for arrhythmogenicity. AB - Cardiac hypertrophy is the physiological adaptation of the heart to chronic mechanical overload. Cardiac failure indicates the limits of the process. Cardiac hypertrophy is only one example of biological adaptation and results from the induction of several changes in gene expression, mostly of the fetal type, including those coding for the myosin heavy chain or the alpha-subunit of the Na+,K(+)-ATPase. From a thermodynamic point of view, the decrease in Vmax allows the heart to produce a normal tension at a lower cost. This process results from changes both in the sarcomere and in the expression of certain membrane proteins. The decrease in calcium transient is determined by several changes in membrane proteins that result in a rather fragile equilibrium in terms of calcium homeostasis. Any abnormal input in calcium will have exaggerated detrimental consequences on a hypertrophied myocyte and may cause automaticity and arrhythmias or an exaggerated response to anoxia in terms of compliance. PMID- 8485831 TI - Modulation of adrenergic receptors and G-transduction proteins in failing human ventricular myocardium. AB - During times of physiological stress, the human heart is able to markedly increase contractility. This response is facilitated by the release of norepinephrine from postganglionic sympathetic nerves and epinephrine from the adrenal gland. These neurotransmitters effect a contractile response by interacting with a transmembrane signaling system within the myocyte sarcolemma consisting of beta 1- and beta 2-adrenergic receptors, the guanine nucleotide binding regulatory proteins Gs and Gi, and the effector enzyme adenylyl cyclase. Activation of this beta-receptor-G-protein-adenylyl cyclase signal transduction complex results in production of the second messenger, cAMP, activation of protein kinase A, and phosphorylation of a group of cellular proteins that are important in excitation-contraction coupling. In contrast to normal human myocardium, the failing human heart is insensitive to adrenergic stimulation. This insensitivity is a result of alterations in the function of this signal transduction pathway, including selective downregulation of the beta 1-adrenergic receptor, uncoupling of beta 2-adrenergic receptors from adenylyl cyclase, and an increase in the functional activity of the inhibitory G-protein. Subtle yet important differences exist between beta-adrenergic neuroeffector mechanisms in idiopathic dilated cardiomyopathy and cardiomyopathy secondary to ischemic heart disease. Most notably, beta-receptors are downregulated to a lesser degree in patients with ischemic heart disease. Therefore, various types of end-stage heart muscle disease may exhibit important pathophysiological differences despite common clinical features and an understanding of the regulatory mechanisms that modulate cardiac signal transduction may have therapeutic implications. PMID- 8485832 TI - Time course and mechanisms of contractile dysfunction during acute myocardial ischemia. AB - BACKGROUND: The purpose of the study was to characterize the functional and metabolic adjustments of a myocardial region subjected to low-flow ischemia. In addition, studies tested whether such myocardium retains an inotropic reserve. METHODS AND RESULTS: Anesthetized swine were studied in which the left anterior descending coronary artery was cannulated and perfused at a constant low level causing regional contractile dysfunction (sonomicrometry for wall thickness) and the appearance of metabolic indicators of ischemia (decrease in creatine phosphate and lactate production) with only slight loss of ATP and glycogen (transmural biopsies). After 85 minutes of low-flow ischemia, dobutamine was infused into the hypoperfused artery as an inotropic challenge. Coronary hypoperfusion for 5 minutes resulted in a 54% reduction of regional systolic wall thickening, reversal of lactate consumption to lactate production, and a significant decrease in creatine phosphate. Subendocardial blood flow was reduced from 0.62 +/- 0.11 (+/- SD) to 0.16 +/- 0.07 mL.min-1.g-1. Prolonged hypoperfusion for 85 minutes resulted in no further change in regional blood flow but a partial recovery of metabolic parameters. Dobutamine infusion after 85 minutes of hypoperfusion increased regional myocardial work. However, again lactate production was significantly increase and creatine phosphate was decreased. Regional coronary hypoperfusion produces a downregulation of regional contractile function in proportion to the blood flow decrease. With prolonged hypoperfusion, after the initial adjustment phase, there is little further change in function, and metabolic markers of ischemia improve. Although the ischemic downregulated myocardium retains a significant inotropic reserve, primarily anaerobic energy production is utilized. CONCLUSIONS: These data are consistent with downregulation being a protective mechanism for the ischemic myocardium to restore an energy supply-demand balance in the face of reduced blood flow. Inotropic stimulation of the downregulated myocardium enhances regional function but at the cost of worsening its metabolic status. Thus, inotropic stimulation of the hypoperfused and downregulated myocardium is probably detrimental to long term viability. PMID- 8485833 TI - Disturbance of the myocardial energy metabolism in dilated cardiomyopathy due to autoimmunological mechanisms. AB - BACKGROUND: After the identification and immunochemical characterization of the ADP/ATP carrier of the inner mitochondrial membrane as an organ- and a conformation-specific autoantigen in myocarditis and dilated cardiomyopathy, we investigated whether an immunoreaction against the ADP/ATP carrier leads to a disturbance of cellular energy metabolism and consequently of myocardial function. METHODS AND RESULTS: Either immunization of guinea pigs with the isolated carrier protein or infection of A/J mice with coxsackievirus B3 induced heart reactive antibodies against the ADP/ATP carrier and led to a disturbance of the cellular energy metabolism: delta Gcyt-mit: 4.9 +/- 0.6 kJ/mol ATP (controls) to 2.3 +/- 1.1 kJ/mol ATP (immunized animals). In the isolated, perfused working heart preparation, the hemodynamic results of these hearts showed a > 50% reduction in external heart work. Because the amount of the decrease of external heart work and the magnitude of the reduction of delta Gcyt-mit showed a very close correlation, it must be suspected that the imbalance of the myocardial energy metabolism is responsible for the impairment of cardiac function. CONCLUSIONS: These data suggest that virus infection of the myocardium as shown for viral myocarditis and dilated cardiomyopathy may lead to a disturbed function of the ADP/ATP carrier and, thus, may be the cause of impaired myocardial function. PMID- 8485835 TI - Heart failure on the basis of hypertension. AB - Arterial hypertension leads to left ventricular hypertrophy. In proportion to increased left ventricular systolic pressure, left ventricular hypertrophy is considered to be of adaptive nature from the point of view of wall stress regulation. In the beginning, left ventricular function is normal, whereas diastolic filling is already compromised by the process of hypertrophy and altered ventricular geometry. In case of ventricular dilation and wall thinning, wall stress increases and leads to an increment in myocardial oxygen demand and a decrease of left ventricular ejection fraction. This is followed by a further decline in intrinsic myocardial contractility and a decrease in the elastic material properties of the myocardium. The structure of the myocardium is characterized by myocyte hypertrophy, a process of reactive and reparative fibrosis and alterations of the coronary microcirculation. Coronary vasodilator reserve is markedly impaired and is likely to initiate a process of malperfusion and malnutrition under increased metabolic demands. Particularly, the combined involvement of myocytes, interstitium, and intramyocardial vasculature appears to predispose to late heart failure after prolonged exposure to chronic pressure overload in arterial hypertension. PMID- 8485834 TI - Cytolytic cross-reactive antibodies directed against the cardiac membrane and viral proteins in coxsackievirus B3 and B4 myocarditis. Characterization and pathogenetic relevance. AB - BACKGROUND: Coxsackievirus B3 and B4 (CVB) myocarditis was assessed by a more than twofold change in titer of the microneutralization tests against enteroviruses within 3 weeks in all patients, by an endomyocardial biopsy indicative of active myocarditis in eight cases, and by pericardial effusion and acute cardiomegaly in two patients. In all endomyocardial biopsies, immunoglobulin binding to the sarcolemma and to the interstitial tissue was demonstrated irrespective of an infiltrate being at the same focus or not. IgG binding was found in nine, IgM and IgA in seven, C3 in C1q in three, and C5b9 in three of 10 patients. In addition, circulating antimyolemmal antibodies (AMLAs) were demonstrated regularly. METHODS AND RESULTS: In this study, for the first time adult human myocytes isolated from atrial appendages during open-heart surgery were used as antigen in the indirect immunofluorescence test: nine of 10 sera of patients with CVB myocarditis demonstrated AMLAs of the homologous type in titers of 1:40-1:320, whereas eight of 10 reacted with rat myocytes (heterologous type) only. Circulating AMLAs fixed complement component C4 in the majority of cases. During the in vitro assay of antibody-mediated cytolysis with vital heart cells, fixation of components C3, C4 to the myolemma in all, of C1q in seven, and of the C3b9 complex in eight of 10 sera was demonstrated after addition of a fresh complement source, indicating the potential of a complement mediated cytolysis being operative. In vitro cardiocytolysis of isolated adult rat heart cells is present in the untreated sera of patients with enteroviral myocarditis and is abolished after adsorption of sera with CVB and with isolated rat heart cells. This indicates functional cross-reactivity of the antimembrane antibodies. To analyze further the cross-reactive epitopes, sodium dodecyl sulfate gel electrophoresis of human and rat sarcolemma and consecutive immunoblots were performed. Cross-reactivity between viral (CVB) and sarcolemmal epitopes could be demonstrated to bands of 220 kd in 10%, 110 kd in 50%, 48 kd in 40%, 35 kd in 40%, and 31 and 28 kd in 30% each. Cardiospecific non-cross reactive epitopes for antisarcolemmal antibodies or AMLAs were membrane proteins of 90 kd and 78 kd in 50%, 72 kd in 90%, 67 kd in 40%, and 45 kd in 50%. Virus specific antibody binding sites for sera included proteins of 33 and 34 kd. CONCLUSIONS: Western blot analysis of sera incubated with cardiac membranes or enteroviral proteins demonstrated that the antibodies are directed to defined epitopes of the sarcolemma. Some antibodies were cross-reactive to enteroviral proteins, indicating that enteroviral infection may be the etiological trigger of an autoreactive myocarditis. The cytolytic property of the patients' sera in vitro suggests in addition that humoral autoreactivity and antigenic mimicry are major pathogenetic principles operative in human enteroviral myocarditis and its sequelae. PMID- 8485836 TI - Tissue renin-angiotensin systems. Their role in cardiovascular disease. AB - BACKGROUND: The identification of the components of the renin-angiotensin system (RAS) in various extrarenal tissues suggested the existence of local renin angiotensin systems with organ-specific functions that may act independently from the plasma RAS. These findings have led to the hypothesis of paracrine-autocrine functions of the RAS, which implies that locally generated angiotensin II mediates effects within one tissue or within one cell. Whereas the circulating endocrine RAS appears to be responsible for acute effects, the tissue RAS seems to participate in more chronic processes such as secondary structural changes and therefore may contribute to the pathogenesis of hypertension as well as other cardiovascular disorders such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. METHODS AND RESULTS: The use of molecular biological techniques has demonstrated that all components of the RAS-renin, angiotensinogen, converting enzyme, and angiotensin receptors-are expressed in several tissues that participate in the regulation of cardiovascular homeostasis. CONCLUSIONS: The therapeutic importance of inhibitors of the RAS, such as converting enzyme inhibitors, is based on their cardioprotective as well as antiproliferative effects and points to a direct involvement of the RAS in the development and preservation of primary hypertension, a pathological condition in which normal or even low plasma renin activity is a common finding. Reversal of cardiovascular structural changes and enhancement of renal sodium excretion by converting enzyme inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS. PMID- 8485837 TI - Diastolic dysfunction in aortic stenosis. AB - Diastolic dysfunction is characterized by an increased resistance to filling with increased diastolic filling pressures. A variety of disorders are associated with diastolic dysfunction, such as hypertrophy, structural alterations of the myocardium with increased fibrosis, myocardial scarring, or infiltrative processes. In addition to these changes, physiological abnormalities of the left ventricle with impaired relaxation, decreased diastolic filling, and increased stiffness of the myocardium can be observed. In patients with aortic stenosis, the most common cause for diastolic dysfunction is left ventricular hypertrophy. Diastolic dysfunction is found in approximately 50% of the patients with normal systolic ejection performance and in 100% of the patients with depressed function. Diastolic function appears either to be more sensitive for detection of abnormal left ventricular function in patients with aortic stenosis or to precede systolic dysfunction or both. Treatment of diastolic dysfunction is usually achieved by aortic valve replacement with regression of left ventricular hypertrophy, but in patients with decompensated aortic stenosis, a reduction of circulating blood volume to reduce diastolic filling pressures, and thus dyspnea, is often indicated. Prognosis of patients with diastolic dysfunction is usually better than that of patients with systolic dysfunction but is clearly worse than that of normal patients. PMID- 8485838 TI - Adaptation to cardiac dysfunction after myocardial infarction. AB - Survival after myocardial infarction decreases with left ventricular dilatation, although dilatation at 4 weeks was found to be compensatory. To study this apparent discrepancy, prospective simultaneous volume and hemodynamic measurements at rest were extended in 39 patients with small and 37 with large myocardial infarctions from 4 days (range, 2-6 days) and 4 weeks (range, 3-5 weeks) to 6 months (range, 5-8 months) after infarction and were repeated during supine bicycle exercise at 50 W. In patients with small infarction, end-diastolic volume (mL/m2) decreased from 4 days to 6 months; ejection fraction (%), stroke volume (mL/m2), and end-systolic volume (mL/m2) remained unchanged. Stroke index rose during exercise at 4 weeks and 6 months. In patients after large infarction (n = 37), left ventricular end-systolic volume index (4 days, 38 +/- 3; 4 weeks, 47 +/- 3*; 6 months, 52 +/- 3*; *p < 0.05 versus 4 days) and end-diastolic volume indexes (4 days, 72 +/- 3; 4 weeks, 86 +/- 5*; 6 months, 92 +/- 5*; *p < 0.05 versus 4 days, +p < 0.05 versus 4 weeks) increased at constant wedge pressure. Stroke index remained restored beyond 4 weeks after infarction (4 days, 35 +/- 2; 4 weeks, 42 +/- 2*; 6 months, 42 +/- 2*; p < 0.05 versus 4 days) and rose during exercise at 4 weeks (rest, 45 +/- 2; exercise, 55 +/- 3; p < 0.05) but not at 6 months (rest, 42 +/- 3; exercise, 45 +/- 3; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485839 TI - Effect of insulin on GABAergic development in the embryonic chick retina. AB - We investigated the role of insulin in GABAergic differentiation in the embryonic chick retina at different embryonic ages using glutamate decarboxylase (GAD) and high-affinity GABA uptake as developmental markers. Both these GABAergic markers exhibit developmentally programmed increases in activity during retinogenesis that also occur in culture. Insulin stimulated GABA uptake in retina neurons at all embryonic ages in a dose-dependent manner and GAD activity by 30% in embryonic retina neurons after 11 days of development. The stimulation of GABA uptake by insulin was blocked by addition of ouabain suggesting a role for the Na+,K+ ATPase. The same concentration of insulin caused a 76% stimulation of protein synthesis in these retinal cells, and previous work demonstrated that insulin also stimulates cholinergic differentiation in the chick retina (Hausman et al., Dev. Brain. Res. 59, (1991) 31-37). Thus, there was no selective stimulation of GABAergic differentiation by insulin but likely a neurotrophic effect. The increase in GAD activity in neurons from post-11-day embryonic neurons contrasts with our previous findings at embryonic days 6-7 where there is little change in GAD activity after addition of insulin. It is possible that the failure of insulin to stimulate GAD activity during early retina development is due to the increased accumulation of GABA in the presence of insulin. GABA levels were increased more than two-fold by 100 ng/ml insulin. PMID- 8485840 TI - Isolation of sympathonectin; a substrate-bound protein which induces preferential growth of sympathetic fibers in vitro. AB - A protein named 'sympathonectin', was purified from chick heart cell-conditioned medium (HCM), on the basis of its ability to direct the neurite outgrowth of cultured sympathetic neurons. The most purified fraction showed a doublet band on SDS-PAGE with an apparent molecular weight of 370 kDa. The biological activity of sympathonectin was over 100 times higher than that of laminin. Immunoblotting with anti-sympathonectin of the 100,000 x g pellet (particulate) fraction of HCM identified a distinct 370 kDa band; this molecule did not react to the anti laminin serum. The immunohistochemical analysis showed that the antibody against sympathonectin stained heart tissue but not skeletal muscle tissue, whereas anti laminin serum stained both tissues. These results suggest that sympathonectin may play a role during sympathetic innervation of target organs. PMID- 8485841 TI - Estrogen receptor immunoreactive neurons in the fetal ferret forebrain. AB - The development of estrogen receptors was studied in the preoptic area/anterior hypothalamus (POA/AH) of fetal male and female ferrets. In males this region includes a nucleus (MN-POA/AH), delineated by Nissl stains, which is not discernible in females. The results reveal the distribution of estrogen receptor containing cells during the period when estrogen is known to induce the differentiation of the male ferret's MN-POA/AH. Brains were taken from ferret kits on days 30, 34, 37 and 40 of a 41-42 day gestation, and were processed utilizing the H222 monoclonal antibody to reveal estrogen receptors. At E30 there were numerous H222 immunoreactive (ir) cells in central regions of the POA/AH. From E30 to E40 there was a striking increase in the number of H222ir cells in the POA/AH. A broad sweep of H222ir cells extended from the ventral POA dorsally and laterally into the caudal POA and AH of both males and females. H222ir cells were not restricted to the region of the MN-POA/AH at any fetal age. H222 immunoreaction product at E30 was restricted to nuclear compartments. By E40, H222ir processes extended from some cells with H222ir nuclei in the medial and lateral POA/AH in both males and females. At the older fetal ages immunopositive cell numbers increased in lateral positions. At E34 and E37 (but not E30) selective ventricular zones, and regions between the hypothalamus and amygdala contained H222ir cells, suggesting the presence of estrogen receptors in cells during migration. Although the amygdala contained a few H222ir cells as early as E34, the cortex lacked H222ir cells even as late as E40. The appearance of H222ir cells in positions suggestive of migration is consistent with the hypothesis that estrogen receptors play some role in determining cell positions in certain regions of the developing nervous system. PMID- 8485842 TI - Immunohistochemical localization of the S-100 beta protein in postnatal cat visual cortex: spatial and temporal patterns of expression in cortical and subcortical glia. AB - The ontogenic expression of the glial-specific protein S100 beta was examined in postnatal cat visual cortex using immunocytochemical methods. Astrocytes in visual cortex and oligodendrocytes in the subcortical white matter exhibited distinct spatio-temporal gradients in their expression of the S100 beta protein. In the visual cortex, S100 beta-immunoreactivity was detected in astroglial cytoplasm, as well as in the extracellular interstitium, in a lamina-specific manner throughout postnatal development. Using double labeling procedures, the S100 beta protein was found to be strictly colocalized with GFAP-immunoreactive astrocytes when GFAP was present. The glial fibrillary acidic protein (GFAP), a marker of mature astrocytes, was not present at high levels until the 4th postnatal week. From the 2nd through 5th postnatal weeks, the expression of S100 beta was highest in the thalamocortical recipient, layer IV, of visual cortical areas 17 and 18. At ages beyond 6 postnatal weeks, S100 beta-immunoreactivity increased disproportionately in supra- and infragranular layers such that areas 17 and 18 were demarcated from adjacent cortices by lower levels in layer IV. The S100 beta protein was also highly expressed in oligodendroglial somata and processes in the subcortical white matter between the 2nd and 6th postnatal weeks. The levels of S100 beta in the subcortical white matter progressively diminished to adult levels, where it was localized only to a few remaining oligodendroglial somata. The differential laminar expression of the S100 beta protein in astrocytes during the period within which the visual cortex exhibits input- and experience-dependent synaptic modifications suggests that astrocytes, possibly via their release of S100 beta, may play a special role in mediating plasticity in visual cortical development. A consistent feature of the appearance of the S100 beta protein was its expression in immature astroglia and oligodendroglia, well before they are considered morphologically mature. This characteristic underscores the potential of S100 beta as a marker of distinct populations of glial cells and of their role in normal and abnormal development. PMID- 8485843 TI - Differentiation of glial precursor cells from developing rat brain in vitro. AB - We have previously shown that enriched preparations of oligodendrocytes from mature bovine brain or 30d rat brain contain 4-10% ganglioside-GD3+ glial precursor cells, which differentiate into astrocytes in culture. These findings are in contrast to those described by others in cultures of neonatal rat brain, which contain precursors that differentiate into both astrocytes and oligodendrocytes. We have extended this study to determine whether the properties of glial precursor cells vary during development. Cells isolated by the same technique from 5-, 10- and 20-day-old rats, were placed in culture and double immunostained at 1,2,3,6 and 10 days in vitro (DIV) for GD3/glial fibrillary acidic protein (GFAP), galactosylceramide (GC)/GFAP, GD3/GC, GD3/antigen O4, GC/O4 and GFAP/O4. After 1 DIV the isolates from 5 day rats contained 30% GD3+ cells, 1% oligodendrocytes (GC+) and 3.5% astrocytes (GFAP+). The corresponding percentages from 10 day rats were: 35% GD3+, 3% GC+ and 3% GFAP+; and from 20 day rats: 28% GD3+, 35% GC+ and 1% GFAP+. Thus the number of oligodendrocytes in the initial isolate increased dramatically between 10 and 20 days. At all 3 ages immature cells were a major component of the total isolate. GFAP+ cells increased rapidly in all cultures. In all cultures the numbers of GFAP+/GD3+ cells reached a maximum and then declined coincident with the increase of GFAP+/GD3- cells, but there were many more of these double-stained cells in cultures from 20 day rats. Moreover, all cultures at 1 DIV contained some GFAP+/GD3- cells. Thus astrocytes appeared to derive both from pre-existing GFAP+/GD3- cells and from GD3+ cells, the latter pathway being more significant in the older rats. GC+ cells increased in cultures prepared from 5 day and 10 day rats, but remained relatively constant in cultures from 20 day rats. The number of GD3+/O4+ cells decreased coincident with an increase of GC+/O4+ cells (all GC+ cells were O4+), but the number of GC+/GD3+ cells was insignificant in any culture from any age animal. These findings in developing animals support the scheme shown by others in neonates that oligodendrocytes derive from GD3+ cells via O4+/GC-intermediate cells. These data show that more GD3+ cells differentiate into oligodendrocytes in 5- and 10 day-old animals than in 20-day-old animals, and a larger percentage differentiate into astrocytes in 20-day-old animals than in the younger animals. The most reasonable explanation of these results is that two committed populations of GD3+ precursor cells exist in the brain, and that the ratio of these populations changes during development. The implication of this conclusion is that bipotential progenitor cells do not persist beyond the neonatal period, but become committed to separate lineages during development. PMID- 8485844 TI - Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development. AB - At early developmental stages in the rat spinal cord (embryonic day 13), when neuronal progenitors are still proliferating, most differentiating neurons express truncated forms of glutamic acid decarboxylase (GAD) (approximately 25 kDa) which are the products of alternative splicing of the GAD67 gene. These truncated proteins do not appear to synthesize gamma-aminobutyric acid (GABA). The amino acid is detected in cells only after alternative splicing of the GAD67 gene generates a full-length, 67 kDa enzymatically active form of GAD. Both the 67 kDa GAD and GABA colocalize and appear diffusely distributed in the cytoplasm of embryonic neurons. GABA does not appear associated with synaptic vesicles until after birth, when its intracellular distribution becomes punctate and it colocalizes with synaptophysin. At this time, it also colocalizes with an immunologically distinct 65 kDa GAD protein encoded by a second GAD gene (GAD65). Expression of different GAD-related proteins with distinct intracellular distributions during development suggests that GABA, the product of these enzymes, may have trophic or metabolic roles during spinal cord differentiation. PMID- 8485845 TI - Ontogeny of synaptophysin and synaptoporin in the central nervous system: differential expression in striatal neurons and their afferents during development. AB - The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast, SO hydridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and 'patches'. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY. PMID- 8485846 TI - Effects of perinatal hypo- and hyperthyroidism on the levels of nerve growth factor and its low-affinity receptor in cerebellum. AB - Deficits or excesses of thyroid hormones during critical periods of mammalian cerebellar development can lead to profound biochemical and morphological abnormalities in this system. The goal of this study was to investigate the effects of perinatal hypo- and hyperthyroidism on the ontogeny of nerve growth factor (NGF) and its low-affinity receptor (p75NGFR) in the rat cerebellum. The concentration of NGF and of p75NGFR immunoreactivity (IR) were measured, several days after birth, in cerebella of rats which had received propylthiouracil (PTU) or thyroxine. NGF concentration was markedly enhanced only on postnatal day 2 (P2) in hyperthyroid rats, whereas in hypothyroid (PTU-treated) rats NGF values were similar to age-matched controls. These observations suggest that thyroid hormone affects NGF synthesis during early periods of cerebellar development. In Purkinje cells of control animals, p75NGFR IR peaked at P10. In hypothyroid rats, the expression of p75NGFR was retarded, peaking at P15, whereas in hyperthyroid rats it was advanced, peaking at P8. The increased p75NGFR IR found in Purkinje cell bodies and the delayed disappearance of p75NGFR IR from the external granular layer of hypothyroid rats suggest different roles for thyroid hormone in the developing cerebellum. We conclude that p75NGFR and NGF are independently regulated by thyroid hormone during critical periods of cerebellar development. The effect of thyroid hormone deficiency on p75NGFR content in Purkinje cells may involve complex mechanisms such as impaired efficiency of axonal transport. PMID- 8485847 TI - Asynaptic expression of the adult nicotinic acetylcholine receptor in long-term cultures of mammalian myotubes. AB - To determine whether synaptic contact is required to express adult-type nicotinic acetylcholine receptors (A-AChR) in developing mammalian muscle, we have examined single-channel AChR activity in primary muscle cultures maintained for up to 29 days. A-AChRs were first expressed after day 12 in culture (CD12), during a period characterized by the accumulation of embryonic acetylcholine receptors (E AChR). The highest rate of A-AChR expression was observed between CD15 and 19, during a period of maximal E-AChR accumulation. Although the level of A-AChR expression between individual patches was quite variable during this period, A AChRs accounted for up to 40% of the events produced by receptors expressed over a 3-day interval. Between CD19 and 29, the density of E-AChRs diminished while the expression of A-AChRs per patch continued to increase but at a lower rate than that observed between CD15 and 19. In 25-29-day cultures, 70.6% of patches exhibited both E-AChR and A-AChR activity, and the percentage of A-AChR events per patch ranged between 0 and 47% with a mean of 11.7 +/- 3.2%. These results demonstrate that endogenous muscle mechanisms promote developmental increases in the expression of A-AChRs in myotubes that have no history of synaptic contact. This conclusion suggests that synaptic imprinting at developing junctions is mediated in part by endogenous muscle mechanisms, and does not require direct neurotrophic activation of epsilon mRNA transcription. PMID- 8485848 TI - The gustatory competence of the lingual epithelium requires neonatal innervation. AB - The rat vallate papilla is bilaterally innervated by the IXth nerve whose axons are required for the normal development of its several hundred taste buds. Temporary denervation during the developmental sensitive period for taste buds prevented most vallate taste buds from forming. Specifically, removing one IXth nerve and crushing the other in 3 day old neonates eliminated axons from the vallate papilla for about 10 days and by adulthood resulted in a mean +/- 1 S.E.M. of 48 +/- 12 vallate taste buds. Two explanations for the shortfall of adult vallate taste buds were evaluated: either 10 days of neonatal denervation impaired the gustatory competence of the vallate papilla, or the IXth nerve's trophic support of taste buds failed to recover after nerve crush on day 3. In adults, it was found that a IXth nerve previously crushed on day 3 would support numerous vallate taste buds (183 +/- 27), provided that the vallate papilla had been continuously innervated by the contralateral IXth nerve during neonatal development. Consequently, taste neurons, whose axons had been crushed on day 3, seemed to survive and retain their trophic capacity to support taste buds in adults. To test for diminished competence of the gustatory epithelium, one IXth nerve was crushed on day 3 while the contralateral IXth nerve was removed. Beginning on day 75, the chorda tympani nerve was substituted for the re innervating axons of the crushed IXth nerve. The cross-innervating chorda tympani ultimately supported only 51 +/- 10 vallate taste buds. In contrast, in vallate papillae that developed without interruption of the contralateral IXth nerve during the sensitive period, the cross-innervating chorda tympani by itself supported more than four times as many vallate taste buds (214 +/- 22). Evidently, a neonatal period of denervation permanently restricts the gustatory competence of the vallate epithelium; nerve-dependent precursors of taste receptor cells probably died or permanently changed their fate. PMID- 8485849 TI - Quantitative analysis of transient GABA expression in embryonic and early postnatal rat spinal cord neurons. AB - GABA expression was investigated using biochemical analysis of spinal cord homogenates and immunocytochemical analysis of cells acutely dissociated from the embryonic and postnatal rat spinal cord. gamma-Aminobutyric acid (GABA) was detected by both methods as early as embryonic day 13 (E13). At E13, the percentage of neurons that were GABA+ was 0.5%. This value increased during embryogenesis, peaked during the first two postnatal weeks to just over 50%, and declined to approximately 20% by the third postnatal week emphasizing the transient nature of GABA expression. At E17 there was a pronounced, positive ventro-dorsal and rostro-caudal gradient of GABA+ cells that persisted until just before birth. At this time the gradients reversed in cervical and lumbosacral regions indicating that GABA immunoreactivity in discrete anatomical regions is also a transient phenomenon. During the embryonic period GABA immunoreactivity was diffusely distributed throughout cell bodies and proximal processes. At E21, both GABA and synaptophysin were present in the same cells. However the two antigens did not co-localize point for point. By postnatal day 21 GABA immunoreactivity appeared in puncta that co-localized entirely with puncta of synaptophysin immunoreactivity. The sizable percentage of neurons that transiently express GABA during development, and the fact that it can be detected prior to the synaptic form of glutamic acid decarboxylase (GAD65), suggest that the amino acid may play a significant role during differentiation before it functions as an inhibitory neurotransmitter. PMID- 8485850 TI - An immunohistochemical study of neuropeptide Y positive sites in the developing human hippocampal formation. AB - Neuropeptide Y (NPY)-positive sites were evaluated by immunohistochemistry in the hippocampal formation of human fetuses aged from 15 to 41 weeks of gestation. Immunopositive cells and fibers were identified in the hippocampus as early as 15 weeks of gestation. These cells were localized in the polymorphic and pyramidal layers and their numbers increased with the age of the fetuses. NPY-positive cells were observed to be closely apposed to blood vessels and some NPY fibers, present mainly in the polymorphic layer, would infiltrate the alveus. PMID- 8485851 TI - Functional development of the neonatal rat retinotectal pathway. AB - Electrophysiological activity in the neonatal rat superior colliculus was recorded to measure neuronal and synaptic activity, and, therefore, functional development. Neonatal rat pups were studied from five days to two weeks of age. The earliest activity in the superior colliculus were spontaneous discharges at a frequency of one unit per animal on postnatal day 6 (P6). Spontaneously discharging units were more numerous at P8, and the number peaked on P10. The first clear response to optic nerve stimulation was seen on P10, with relatively long and variable latencies. By P14, electrically evoked responses had much shorter latencies. The results are in line with the first response to light flash in the superior colliculus at P12/13. The evidence suggests that functional development of the rat retinotectal pathway begins at the end of the first week after birth, and that much of the functional maturation occurs mainly during the second week after birth. PMID- 8485852 TI - Retinoic acid-induced differentiation of a human neuroblastoma cell line alters muscarinic receptor expression. AB - Muscarinic receptor density increased by approximately 36% after differentiation induced by retinoic acid (Bmax, control = 126 +/- 13 fmol/mg protein; Bmax, retinoic acid-treated = 170 +/- 17 fmol/mg protein; P < 0.05), corresponding to a 170% increase in receptor content per cell. The affinity of [3H]NMS for the receptors was somewhat lower in the retinoic acid-treated cells (Kd, control = 0.14 +/- 0.04 nM; Kd, retinoic acid-treated = 0.25 +/- 0.04 nM; P < 0.05). Reverse transcriptase/polymerase chain reaction analysis using subtype-specific primers revealed that undifferentiated Sk-N-SH cells transcribed mRNA for all 5 receptor subtypes; this pattern was not affected by retinoic acid treatment. [3H]NMS displacement curves with subtype selective receptor ligands (pirenzepine, m1; AFDX-116, m2; 4-DAMP, m3) indicated the predominant expression of m3 and m1 receptor subtypes, and differentiation did not affect the pharmacological profile of the expressed receptor populations. The present results indicate that differentiation induces selective changes in the expression and activity of muscarinic receptors in a neuronal cell line. PMID- 8485853 TI - Long-term alterations in brain function following cocaine administration during the preweanling period. AB - This report examines the long-term effects of cocaine exposure during postnatal days (P) 11-20 on the metabolic function of major central neuronal systems. Cocaine (50mg/kg) or vehicle was administered subcutaneously to rat pups during P 11-20. At 60-64 days of age, the rats were examined for cerebral glucose metabolic patterns. In cocaine-treated females 18 of the 46 structures evaluated showed increased metabolic rates including 5 of 6 structures within the motor system and 7 of 17 limbic structures. No decreased rates were seen. In males, cocaine had no effects in the motor structures or hypothalamus while 2 of 17 structures within the limbic system showed decreased rates of glucose utilization and 2 of 11 structures within the sensory systems showed increased rates. These results indicate that female rats show greater long-term metabolic effects than males and that cocaine exposure during P 11-20 produces different metabolic effects than cocaine exposure during P 1-10 which we previously reported. PMID- 8485854 TI - Developmental changes in seizure susceptibility in carbonic anhydrase II deficient mice and normal littermates. AB - Mice deficient in carbonic anhydrase II (CA II) were tested along with their normal littermates for susceptibility to seizures induced by flurothyl and loud sound at ages 10-180 days. In the flurothyl seizure model, CA II-deficient mice displayed increased resistance to clonic seizures from 32 to 90 days of age, whereas tonic-clonic seizures were suppressed at all ages. The mortality of CA II deficient mice was significantly decreased at ages 19-40 days. The incidence of sound-induced seizures was very low and no difference between CA II-deficient and normal mice was found. The anticonvulsant effect of CA II deficiency appears to be dependent on seizure model and seizure type and to have age-specific characteristics. PMID- 8485855 TI - Effects of probucol and pravastatin on plasma lipids, activities of postheparin lipoprotein lipase, and lecithin cholesterol acyltransferase and apo A-I containing lipoproteins with and without apo A-II in patients with moderate hypercholesterolemia. AB - In this study, plasma HDL fractions were separated by ultracentrifugation and apo A-I containing lipoproteins (A-I Lp) were then isolated using anti-apo A-I immunoaffinity chromatography. The A-I Lp were further separated into two fractions with the use of anti-apo A-II immunoaffinity chromatography. One fraction, Lp A-I, contained apo A-I without apo A-II, while the other, Lp A-I/A II, contained both apo A-I and apo A-II. These techniques were applied to investigate the changes in HDL apoprotein composition in hypercholesterolemic subjects treated with either probucol or pravastatin. Treatment with probucol (500 mg/day) or pravastatin (10 mg/day) reduced mean plasma total cholesterol concentrations by 24% (p < 0.01) and 16% (p < 0.05), respectively. Both drugs caused some reduction in lipoprotein lipase activity, but neither had any influence on the activity of hepatic triglyceride lipase or lecithin cholesterol acyltransferase. Their effects on HDL-cholesterol levels and apoprotein composition differed markedly. Probucol significantly decreased the HDL cholesterol concentration, the plasma apo A-I/apo A-II ratio, and the number of large particles of diameter greater than 10.4 nm. When the ratios of Lp A-I and Lp A-I/A-II for the probucol-treated subjects were compared with those in the normolipidemic controls, and with the ratios before and after administration of probucol, a remarkable decrease in the level of Lp A-I was apparent. It is presumed that the decrease in HLD-cholesterol by prolonged probucol administration reflects the decrease of Lp A-I more than the decrease of Lp A-I/A II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485856 TI - Human erythrocyte superoxide dismutase in adults, neonates, and normal, hypoxaemic, anaemic, and chromosomally abnormal fetuses. AB - An enzyme-linked immunosorbent method is described for the assay of human erythrocyte superoxide dismutase (SOD). The method was specific and precise as well as simple, economical, and reliable. The mean levels of adult SOD with SD were 652 +/- 122 mg/kg hemoglobin (Hb) for males and 635 +/- 100 mg/kg Hb for females. In neonates the levels were 528 +/- 92 mg/kg Hb. Normal fetal levels at 20-36 weeks gestation were 421 +/- 90 mg/kg Hb. Mean SOD levels in hypoxemic growth-retarded fetuses and in anemic fetuses from red cell iso-immunised pregnancies (before their first intrauterine blood transfusion) were the same as those in normal fetuses. However, in a case of trisomy 21 the fetal level of SOD was significantly increased. PMID- 8485857 TI - Serum macro creatine kinase type 2 in asphyxiated newborn infants. AB - The presence of macro creatine kinase type 2 (MCK2) activity was noted in the serum of seven out of 32 newborn infants with perinatal asphyxia or birth trauma. MCK2 isoenzyme, when present, represented 15-35% of the total creatine kinase (CK) activity. The clinical and biochemical features of the seven MCK2-positive and 25 MCK2-negative newborns were compared. The infants with MCK2 activity were all males and clinically appeared to be more severely injured, requiring longer hospitalization. Total CK activity was similar in the two groups and CK-MB and CK BB isoenzyme fractions were present in a similar proportion of infants in both groups. Two infants in each group had long-term neurological disorders. Although the presence of MCK2 has been noted in adult patients with end-stage metastatic solid tumors, the presence of this isoenzyme has not previously been reported in newborn infants. PMID- 8485858 TI - HDL particle measurements: impact for diagnosis and therapy. PMID- 8485859 TI - Current controversies about galactosemia. PMID- 8485860 TI - Rheumatoid factors. AB - Rheumatoid factors (RFs) have been studied for over 50 years and are probably the most written about of any antibody. Nevertheless, the etiology of these RFs and the precise role they play in the pathogenesis of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) remain a major interest. When RFs participate in the generation of inflammation in RA and JRA, they probably do so by forming immune complexes (IC) or are themselves able to bring about the inflammatory response. Their presence has been associated with more severe disease, vasculitis, and systemic symptoms. The present review summarises the literature over the last few years on new and interesting findings on RF. This review covers an update on RF assays, RF cross-reactivity, specificity studies, immune complex formation, RF lymphocyte studies, and RF binding. PMID- 8485861 TI - Characterisation of human lung elastin-derived peptides. AB - The enzymatic breakdown of human lung elastin by leukocyte elastase precedes the development of pulmonary emphysema, and releases elastin-derived peptides (EDPs) into the circulation. While raised levels of EDPs measured by enzyme-linked immunosorbent assay (ELISA) have been proposed as a possible marker for early detection of emphysema, average normal values of EDPs measured by different investigators have differed by up to a factor of 1000. Standardisation of the methodology for elastin purification and EDP production in vitro is required to ensure the accuracy of EDP measurements in vivo, because antiserum used in the ELISA is raised against the EDPs produced in vitro. In the present study elastin was purified from human lung by sequential biochemical extraction, and solubilised by leukocyte elastase. Molecular weight distribution of EDPs produced by partial and complete elastin digestion were compared by gel exclusion chromatography. A method for successful separation of EDPs by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) is reported. The implications of these results for further immunological characterisation of these peptides are discussed with a view to standardisation of the techniques employed for the measurement of EDPs in vivo. PMID- 8485862 TI - Comparative study of two commercial enzymatic kits for determining oxalate concentrations in urine. AB - We performed a comparative study of two commercial kits for determining oxalate in urine. These were: (a) an oxalate decarboxylase-based assay (Boehringer Mannheim); (b) an oxalate oxidase-based assay (Sigma). The within-run and between run imprecision were found to be similar in both methods. The recovery was 94% with the oxalate decarboxylase method. The pH of the specimen had a major effect on the recovery obtained by the oxalate oxidase method (66-86% at pH = 2.5 and 37 68% at pH = 1.5). The decarboxylase method was linear up to at least 2224 mumol/L and the oxidase method was linear up to at least 890 mumol/L. We also studied the interference of ascorbic acid in both techniques and found a positive bias with the oxidase method and a negative bias using the decarboxylase method. The correlation coefficient was 0.592. PMID- 8485863 TI - Analysis of charge of kappa and lambda chain-containing serum immunoglobulin A by immunoblotting and densitometry. AB - A novel method for studying the charge distribution of different subclasses of serum immunoglobulin A (defined by the light chains) is described. Affinity chromatography purified immunoglobulins were focused in polyacrylamide gel and were then transferred electrophoretically onto nitrocellulose membranes. The transferred immunoglobulins were detected by rabbit antiserum to human kappa (kappa) or lambda (lambda) chain, swine antirabbit IgG, rabbit anti-peroxidase antibodies and peroxidase, together with a substrate solution comprising H2O2 and diaminobenzidine. Finally, the developed membranes were made transparent with Triton-x 114, scanned at 485 nm with a densitometer to obtain quantitation of charge distribution. PMID- 8485864 TI - Detecting the renal effects of cadmium toxicity. PMID- 8485865 TI - Lipase in serum--the elusive enzyme: an overview. AB - Lipase is a glycoprotein with 420-449 amino acid residues and a M(r) of 46,000 56,000 for pancreatic lipase and 32,000-39,000 for serum lipase. Lipase is present in the pancreas, intestines, and a variety of other tissues. The concentration gradient between pancreatic tissue and serum lipase is approximately 20,000-fold. Serine, as part of an Asp-His-Ser triad, is the nucleophilic residue essential for catalysis. Lipase differs from other esterases by the presence of a hydrophobic recognition site. The optimal pH is between 7.5 and 10.0, depending on the reaction condition; the pI for the various forms of the enzyme has been reported as 5.80 and 5.85; 6.4, 6.8, and 7.0; and 7.4 for a purified fraction. Several authors report the presence of two molecular forms in the pancreas and three electrophoretic bands with lipolytic activity. In normal serum two bands have been observed; in pancreatitis as many as four bands have been seen. Lipolytic activity may not always be due to lipase. Assays specific for lipase require a triglyceride as substrate as well as the presence of colipase (a water-soluble and heat-stable protein, essential for lipase action), a secondary bile salt, and Ca2+. The clinical sensitivity of all modern assays is high because of selection of a low decision limit; the clinical specificity varies greatly but can be improved by increasing the cutoff point. Lipase determinations in pancreatitis are superior to amylase determinations. The reasons for the great variability of reports regarding the clinical utility of lipase are discussed, and the clinical utility of lipase determinations is summarized. PMID- 8485866 TI - A quantitative measure of nonlinearity. AB - Quantitative measures of the nonlinearity of an analytical method are defined as follows: the "(dimensional) nonlinearity" of a method is the square root of the mean of the square of the deviation of the response curve from a straight line, where the straight line is chosen to minimize the nonlinearity. The "relative nonlinearity" is defined as the dimensional nonlinearity divided by the difference between the maximum and minimum assayed values. These definitions may be used to develop practical criteria for linearity that are still objective. Calculation of the nonlinearity requires a method of curve-fitting. In this article, we use polynomial regression to demonstrate calculations, but the definition of nonlinearity also accommodates alternative nonlinear regression procedures. PMID- 8485867 TI - International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. III. Comparability of apolipoprotein A I values by use of international reference material. AB - In the third phase of the International Federation of Clinical Chemistry (IFCC) study for the standardization of apolipoprotein (apo) measurements, the preparation SP1-01, selected as the candidate international reference material for apo A-I, was investigated for its ability to transfer an accuracy-based value to the immunoassay calibrators and to produce comparability of the values for patients' samples. An apo A-I value of 1.50 g/L (SD 0.08 g/L) was assigned to SP1 01 by a highly standardized RIA calibrated with purified apo A-I for which the mass value had been determined by amino acid analysis. According to a common detailed protocol, the participants transferred the mass value from SP1-01 to the calibrator of each method. To confirm that uniformity of calibration ensures comparability of the values over a wide range of apo A-I values, each laboratory analyzed 50 fresh-frozen samples from individual donors, using an approach similar to that adopted by the Cholesterol Reference Laboratory Network. The consensus mean value for each sample was in excellent agreement with the value assigned by the Northwest Lipid Research Laboratories, with the average absolute bias between assigned and consensus value being 0.01 g/L. The among-laboratory CV on each of the 50 samples ranged from 2.1% to 5.6% (mean 3.6%), demonstrating that comparable apo A-I results can be obtained by a variety of immunochemical methods through the use of certified reference material. Based on the results obtained in these studies, SP1-01 has been approved as Apolipoprotein A-I International Reference Material by the World Health Organization. PMID- 8485868 TI - Increased phospholipase A activities in sera of intensive-care patients show sn-2 specificity but no acyl-chain selectivity. AB - Phospholipase A (PLA) activities were measured by high-performance liquid chromatography in two enzyme preparations purified from human duodenal juice and a serum pool as well as in 52 sera from 31 intensive-care patients with various diseases. On the basis of a position-specific fatty acid analysis of the natural substrate ("soybean lecithin") from a commercial PLA kit, serum activities of PLA1 could be clearly distinguished from those of PLA2, which is not possible in the usual measurements made with single-label radioactive substrates. Independent of the type of disease, all sera with highly increased PLA activities (40-200 U/L) showed nearly pure PLA2 characteristics without any preference among oleic, linoleic, and linolenic acid in the sn-2 position of the glycerophospholipid substrate. Nevertheless, very low PLA1 activities (< or = 5 U/L, most likely due to heparin perfusion therapy) could also be detected by palmitic and stearic acid release from the sn-1 position, leading to small changes in fatty acid release patterns of sera with low PLA activities. Measurements with sera from heparin treated volunteers demonstrated that heparin therapy may initially contribute as much as 22 U/L to increased PLA1 activities but is not important under prolonged therapy. The absence of selectivity with respect to acyl-chain desaturation supports the concept of serum PLA2 as an acute-phase protein rather than a regulator of the arachidonic acid cascade. PMID- 8485869 TI - Lipid peroxidation and trace element status in diabetic ketotic patients: influence of insulin therapy. AB - Lipid peroxidation is known to accelerate aging and microvascular lesions in diabetic patients. We studied the acute influence of improved glycemic control on the concentrations of plasma lipid peroxidation intermediates [malondialdehydes (MDA), organic hydroperoxides (OHP)] in ketotic insulin-dependent diabetic patients, as well as the interplay of enzymes such as glutathione peroxidase (GPX) and CuZn superoxide dismutase (CuZn-SOD), and trace elements (Zn, Se, Cu) postulated to be involved in free radical protection. These plasma components were measured on the first day of hospitalization (T0) and when the patient had attained a stable glycemic state after continuous insulin treatment (T1). Plasma MDA and OHP concentrations were high at the beginning of the study but approached reference values after glycemic equilibration. Plasma zinc concentrations were significantly (P < 0.05) decreased during the ketotic state, but also approached reference values with glycemic equilibration. Plasma selenium concentrations and GPX activity were relatively unchanged between T0 and T1. Erythrocyte GPX activity measured at T1 in six patients was below the reference values, whereas CuZn-SOD activity was not affected. Our results show that enhanced lipid peroxidation is associated with decreased zinc plasma concentrations in ketotic patients and underline the beneficial effects of continuous insulin infusion. The mechanisms involved are still unclear but may indicate the importance of extracellular zinc transfer secondary to glycemic disorders. PMID- 8485870 TI - Analysis for bismuth in tissue by electrothermal atomic absorption spectrometry. AB - We developed a simple method for the analysis of bismuth (Bi) in biological tissue, using wet digestion for sample pretreatment. Bi was determined by electrothermal atomic absorption spectrometry with platinum as a matrix modifier to decrease the volatility of Bi. The furnace program included a gas stop for sensitivity enhancement. Analytical performance was established for Bi in kidney, liver, brain, and bone. As little as 25 ng/g wet weight can be detected in the most concentrated digests. Homogenization of bone was necessary before digestion, and its matrix showed the strongest interference. In rats exposed orally to colloidal bismuth subcitrate for 14 days, the metal could be detected in liver, kidney, and spleen but not in brain and bone. In the tissues of 12 patients who died from non-Bi-related causes, no Bi were present in kidney in the other 2. PMID- 8485871 TI - Separation of beta-carotene and lycopene geometrical isomers in biological samples. AB - The analysis of beta-carotene and lycopene, the two predominant carotenoids in human serum and tissues, was extended to the level of geometrical (cis-trans) isomers by using an improved reversed-phase HPLC methodology. We separated five geometrical isomers of beta-carotene and seven of lycopene in human serum and tissues. 13-cis-beta-Carotene was identified as the predominant cisisomer in human serum, contributing about 5% to total beta-carotene. In tissue, however, considerable amounts of 9-cis- and traces of 15-cis-beta-carotene were also detected. In contrast to beta-carotene, the lycopene isomer patterns in human serum and tissues are quite similar. PMID- 8485872 TI - Glycated calmodulin from platelets as an index of glycemic control. AB - In an effort to test whether a significant fraction of calmodulin would become glycated within the life span of the platelet (10-14 days), we monitored the kinetics of calmodulin glycation in vitro. Under the conditions we used, the fraction of glycated calmodulin reached a maximum (approximately 21%) within 10 days. We then extended the studies to human subjects. The intraplatelet concentrations of calmodulin and glycated calmodulin from age-matched type I diabetic subjects were monitored by a combination of m-aminophenylboronate affinity chromatography and enzyme-linked immunosorbent assay. The results indicate that the concentrations of total intraplatelet calmodulin (nonglycated plus glycated) were not dependent on the glycemic state of the subjects. Data from control and diabetic subjects showed a poor correlation between the concentrations of glycohemoglobin and of glycated calmodulin. However, a better correlation was obtained when glycated calmodulin concentrations were compared with those of serum fructosamine. The fraction of glycated calmodulin in the control population (7.71% +/- 0.75%) was significantly (P < 0.05) different from that of the diabetic population (21.6% +/- 1.26%). Given that the clinical role of the fructosamine assay remains controversial, estimation of glycated calmodulin in platelets might be useful as a short time-window index of glycemic control. PMID- 8485873 TI - Fast HPLC determination of serum free fatty acids in the picomole range. AB - We developed a method for determining individual free fatty acids in serum by using a modified one-step Dole extraction, derivatization, and a new high performance liquid chromatographic (HPLC) separation. Sample handling is minimized to a single transfer of the fatty acids (upper layer of the Dole extract), which are readily derivatized at 85 degrees C with p-bromophenacyl bromide without significant hydrolysis of esterified fatty acids. The derivatization mixture is directly injected into the HPLC apparatus. The new method, which uses C6 (3-microns particle) column material and an isocratic acetonitrile-water eluent, separates nearly to baseline 12 of the physiologically most abundant long-chain fatty acids (C12-C22) in < 20 min with a detection limit of approximately 2 pmol. It is therefore suitable for routine analysis even with basic HPLC equipment and can easily analyze a series of 10-20 samples in about 2 h including extraction until first results are available. The method is also applicable to other matrices than serum, e.g., for determination of precursor fatty acids such as arachidonic acid in platelets or of fatty acid patterns liberated by lipases or phospholipases A1/A2 in test systems. PMID- 8485874 TI - International cooperation in analytical chemistry: experience of antidoping control at the XI Pan American Games. AB - We describe the experience of the international cooperation carried out for antidoping control at the XI Pan American Games. A temporary accreditation was granted by the International Olympic Committee to the accredited laboratory of Barcelona (Spain) to set up a Doping Control Laboratory in Havana. Two other laboratories from Mexico and Cuba contributed personnel, materials, and instrumentation. The main issues associated with the preparation and organization of the project are described. During 16 days, 741 urine samples were tested for stimulants, narcotics, anabolic steroids, beta-blockers, diuretics, cannabinoids, local anesthetics, and human chorionic gonadotropin by gas-liquid chromatography, gas chromatography/mass spectrometry, high-performance liquid chromatography, and immunoassay techniques. Analytical methodologies, quality-control strategies, and the main results are reported. PMID- 8485875 TI - Intra- and interlaboratory sources of imprecision in drug measurements by different techniques. AB - We compared the intra- and interlaboratory precision of seven techniques used to measure eight antiepileptic drugs, digoxin, and theophylline by using data from the international Healthcontrol external quality-assessment scheme. Scheme participants were supplied blind with 6 or 12 sets of duplicate lyophilized serum samples. Each set contained different drug concentrations, and duplicates were analyzed separately, 1 to 6 months apart. The intra- and interlaboratory components of assay variance were isolated and compared by Bartlett's test for homogeneity of variance. Fluorescence polarization immunoassay (Abbott) showed the best overall intra- and interlaboratory performance for a range of analytes. The largest intralaboratory errors were produced by techniques using the Syva EMIT assays. Our analysis of the data shows that for most analyte/technique combinations, intralaboratory sources of variation were more important than interlaboratory sources. Gains in assay precision will therefore result from attention to internal laboratory procedures. PMID- 8485876 TI - Characterization procedure for ion-selective electrode assays of magnesium activity in aqueous solutions of physiological composition. AB - A magnesium ion-selective liquid membrane electrode based on a synthetic neutral carrier is presented. The selectivity for Mg2+ over Na+, K+, and H+ is sufficient for assays in the physiological range, but a chemometric correction of approximately 10% is still necessary for the Ca2+ interference. We optimized the membrane composition especially with respect to selectivity and accuracy by performing a new characterization procedure in which we simulated the variety of blood serum samples with 10 aqueous solutions. After a three-point calibration, these solutions were measured alternately with the middlerange calibrator for 3 min. The magnesium activity was evaluated after correcting for the calcium interference according to the Nikolsky equation. The selectivity coefficient, KpotMgCa, was itself fitted to give the minimum deviations from the assigned magnesium activities. Electrodes with an optimized membrane composition show an average deviation from theoretical activity values of about 1.6% with logKpotMgCa = -0.8. PMID- 8485877 TI - Evaluation of seven Cholestech L.D.X analyzers for total cholesterol determinations. AB - We assessed the performance of seven Cholestech L.D.X lipid analyzers under tightly controlled laboratory conditions for accuracy and precision in accordance with analytical guidelines of the National Cholesterol Education Program (NCEP). Venous heparinized whole blood (VB) and plasma (VP), venous serum (VS), and capillary fingerstick whole blood (FB) were collected from 18 individuals. Total cholesterol (TC) concentration was measured in VB, VP, and VS on all seven instruments. Three instruments were used for TC measurements of FB. Reference cholesterol values for each individual were generated in the same laboratory with a standardized method. The within-run coefficients of variation (CVs) for all instruments with a Level I pool (1560 mg/L, n = 10) ranged from 1.3% to 1.8% (mean = 1.59%). The between-run CVs with the same pool ranged from 2.2% to 3.4% (mean = 2.84%, n = 10). Correlation coefficients derived from comparison of total cholesterol values generated by the instruments for each specimen type vs the reference cholesterol values were all > 0.97. The average bias for all instruments for each sample type was 1.9% (FB), 4.3% (VB), 6.6% (VP), and 7.0% (VS). Predicted cholesterol concentration for each sample type from regression curves for total cholesterol at the suggested NCEP clinical decision cutoff values of 2000 and 2400 mg/L, respectively, were 2049 and 2431 mg/L for FB, 2081 and 2469 mg/L for VB, 2122 and 2522 mg/L for VP, and 2121 and 2521 mg/L for VS. PMID- 8485878 TI - Interference of lysophosphatidylcholine in hormone radioimmunoassays. AB - The interference of synthetic and naturally occurring detergents in immunoassays is well documented. In the present study, we evaluated the effect of lysophosphatidylcholine (LPC) and found that the lysophospholipid interfered with formation of the antigen-antibody complex in hormone immunoassays. In the presence of LPC (100 mumol/L), progesterone was overestimated by 29%. Furthermore, physiological concentrations of LPC (140 mumol/L) interfered with the assays of cortisol, progesterone, and aldosterone, resulting in overestimations of 35%, 30%, and 27%, respectively. The addition of albumin decreased the interference by LPC to 7% in the assay of cortisol and progesterone when the LPC:albumin ratio was unity. Adding cholesterol (100 mumol/L) also reduced by 50% the interference induced by LPC. Finally, treating plasma to increase the endogenous LPC concentration also resulted in interference in the cortisol assay. Thus, interpretation of the results of these assays should take into consideration the endogenous serum albumin:LPC ratio. PMID- 8485879 TI - Assay of complexed alpha 1-antichymotrypsin in plasma. AB - We introduce an assay to measure complexed alpha 1-antichymotrypsin in human plasma. The assay works on the principle that the target proteinase cathepsin G has a very high affinity to the surface of microtiter plates, even if these surfaces are blocked with albumin and Tween 20. alpha 1-Antichymotrypsin, when complexed to cathepsin G, is thus immobilized and can be detected with specific antibodies. The mean (SD) concentration of alpha 1-antichymotrypsin in 50 healthy individuals was 1.73 (0.58) nmol/L. The detection limit was 0.84 nmol/L. The results of the assay are linear to at least 14 nmol/L. We propose to use this assay for diseases in which increased turnover of alpha 1-antichymotrypsin or cathepsin G can be expected to clarify further the function of this enzyme inhibitor system. PMID- 8485880 TI - Reduced bovine hemoglobin solution evaluated for use as a blood gas quality control material. AB - We evaluated a new commercially available partially purified reduced bovine hemoglobin solution (RBHS) and a new tonometer for use in the quality control of blood gas analyzers. RBHS is manufactured in three different formulations, each corresponding to three different bicarbonate-buffering capacities and concentrations of total hemoglobin (ctHb). The P50 for each formulation of RBHS was determined to be as follows: 30.6 mmHg (4.08 kPa) for Level 1, 29.1 mmHg (3.88 kPa) for Level 2, and 28.2 mmHg (3.76 kPa) for Level 3. When RBHS and human blood samples were tonometered at three clinically significant values of PO2 and PCO2, the recovered values for PO2 and PCO2 in RBHS were comparable with those of the tonometered whole blood. Each level of RBHS also produced precise pH (SD < or = 0.006 pH units) and ctHb (SD = 1.0 g/L) values. In addition, when the temperature of a sample chamber was intentionally altered, the changes in RBHS blood gas values closely approximated the changes seen with human blood. RBHS shows more thermal sensitivity than either perfluorocarbon emulsions or aqueous buffers, which are currently being used as quality-control and proficiency testing materials. PMID- 8485881 TI - Role of antibody valency in hapten-heterologous immunoassays. AB - We studied the effects of hapten heterology on immunoassays of triiodothyronine (T3), digoxin, and cortisol, in a format involving labeled monoclonal antibodies and immobilized, protein-conjugated ligands. Replacing the homologous conjugated ligands T3, digoxin, and cortisol with their respective analogs diiodothyronine, digitoxin, and corticosterone led in each case to a decrease in the midpoint of displacement (ED50) for the same zero-dose signal. The mechanism of this phenomenon was studied by converting the bivalent anti-T3 to a monovalent whole antibody (bispecific monoclonal anti-T3 x anti-glucose-6-phosphate dehydrogenase) by cell fusion. The monovalent antibody was effective as a tracer in the homologous T3 assay, but generated a very low zero-dose signal with the heterologous solid phase, thus precluding sensitivity enhancement. On the basis of these results and additional kinetic and double-labeling experiments, we propose that the use of hapten heterology relies on bivalent binding of the antibody to the solid phase to compensate for a lower intrinsic affinity. This binding mechanism leads to lower assay concentrations of the ternary complex analyte-labeled antibody-immobilized hapten, thereby providing enhanced sensitivity. PMID- 8485882 TI - Measurement of urinary sugars by HPLC in the estimation of intestinal permeability: evaluation in pediatric clinical practice. AB - Determinations of the permeability of the intestine to various sugars have been used to assess intestinal mucosal abnormalities, but the widespread application of such tests has been prohibited by the complexity of most classically used techniques. In this study, we evaluated the sensitivity and practicability of using HPLC to estimate intestinal permeability, with mannitol and lactulose as mono- and disaccharides, respectively. The results of the permeability tests were compared with those of intestinal biopsy in 20 children. All patients with an abnormal intestinal biopsy showed a low mannitol recovery, and the patients with allergic symptoms showed a high lactulose recovery. Our preliminary data suggest that HPLC is reliable, gives results comparable with those of other methods, and is a practical way to determine intestinal permeability noninvasively. PMID- 8485883 TI - Monitoring cancer antigen 125 in serum of ovarian cancer patients after administration of 131I-labeled F(ab')2 fragments of OC125 antibody. AB - We evaluated the effect of repeated administration of OC125 F(ab')2 fragments on cancer antigen (CA) 125 determination in 210 serum samples from 30 patients. We found falsely high CA 125 concentrations in 142 (68%) samples, using a homologous CA 125 enzyme immunoassay (EIA) with OC125 antibodies. The Truquant OV2 method, which involves two other murine antibodies, and the IMx CA 125 method, which uses sheep antibodies as capture antibodies, resulted in only slightly increased (false-positive) values in some samples with exceptionally high CA 125 EIA values. We measured falsely low CA 125 values in 37 (18%) samples with the Truquant OV2 method. Interferences could be eliminated by removal of serum IgG. Our results suggest that interferences are to some extent caused by anti idiotypic IgG induced by OC125 administration. Assays involving nonmurine anti-CA 125 antibodies as capture antibodies seem to be most suited for CA 125 determination after OC125 treatment, but in every case an apparent increase of CA 125 after OC125 infusion should be validated. PMID- 8485884 TI - 3-Hydroxydicarboxylic and 3-ketodicarboxylic aciduria in three patients: evidence for a new defect in fatty acid oxidation at the level of 3-ketoacyl-CoA thiolase. AB - Three patients presented with evidence of a fatty acid oxidation disorder. Analysis of urinary organic acids by gas chromatography/mass spectrometry demonstrated the presence of medium-chain (C6-C12) dicarboxylic, 3 hydroxydicarboxylic, and 3-ketodicarboxylic acids in all three urines. 3 Ketodicarboxylic aciduria is reported for the first time here, as are the mass spectra for 3-ketosuberic, 3-ketosebacic, and 3-ketododecanedioic acids and the oximated spectrum for 3-ketoadipic acid. The presence of 3-ketodicarboxylic acids suggests a defect at the level of a long-chain 3-ketoacyl-CoA thiolase, an enzyme for which a deficiency state has not previously been described. Our patients may represent the first cases of a long-chain thiolase defect. PMID- 8485885 TI - Sigma diagnostics: pioneer of kits for clinical chemistry. PMID- 8485886 TI - Calibration of automated thyrotropin assays. PMID- 8485887 TI - Within-subject variation of thyroxine and triiodothyronine concentrations in serum. PMID- 8485888 TI - Effect of parturition on serum alpha 1-antiprotease (alpha 1-antitrypsin) PMID- 8485889 TI - Interferences of bilirubin, ascorbic acid, dipyrone, and D-penicillamine in two assays of 5'-nucleotidase. PMID- 8485890 TI - Biological variation of lactate and pyruvate in blood. PMID- 8485891 TI - Incomplete separation of erythrocytes from serum causes significant error in the IMx free triiodothyronine assay. PMID- 8485892 TI - Growing use of nonisotopic CA 19-9 immunoassays increases between-laboratory variability. PMID- 8485893 TI - Interference in coupled-enzyme assay of urea nitrogen by excess endogenous enzyme. PMID- 8485894 TI - Mn- and Cu,Zn-superoxide dismutase activities during acute myocardial infarction. PMID- 8485895 TI - Effect of light on serum B12 and folate stability. PMID- 8485896 TI - Desirable performance criteria for quantitative measurements in medical laboratories based on biological analyte variation--hindrances to reaching some and reasons to surpass some. PMID- 8485897 TI - Detection of dystrophin with a modified western blot technique in muscle tissue extracts. PMID- 8485898 TI - False-positive ketone reactions in CAP surveys. PMID- 8485899 TI - IgA anti-lipoprotein antibodies in autoimmune dyslipidemia are restricted to IgA1 subclass. PMID- 8485900 TI - Problems of C-reactive protein determination in patients with monoclonal immunoglobulins. PMID- 8485901 TI - Autoantibody specific for lactate dehydrogenase isoenzyme 4. PMID- 8485902 TI - High concentrations of eosinophil-derived neurotoxin in patients' urine mimic lysozyme far-cathodic bands in agarose gel electrophoresis. PMID- 8485903 TI - Stability of acetoacetate after venesection. PMID- 8485904 TI - Methemoglobin determinations in cerebrospinal fluid have low clinical utility. PMID- 8485905 TI - CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions. AB - The C3 receptor CR3 is expressed on phagocytic cells, minor subsets of B and T cells, and natural killer (NK) cells. It has important functions both as an adhesion molecule and a membrane receptor mediating recognition of diverse ligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. The receptor is capable of undergoing an activation event that regulates both its specificity for various ligands and its ability to mediate phagocytosis or extracellular cytotoxicity. Certain bacteria express carbohydrates or lipopolysaccharides (LPS) that can bind to and activate CR3, allowing the receptor to assume its activated state. Soluble beta-glucan derived from the yeast Saccharomyces cerevisiae is a particularly potent stimulator of CR3, and produces an activated state of the receptor that permits neutrophil phagocytosis of iC3b-coated erythrocytes or NK, cell cytotoxicity of iC3b-coated tumour cells, that are normally resistant to NK cells. PMID- 8485906 TI - Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2. AB - The effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 x 10(6) U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 therapy ranged between 23 and 64 U/ml and was proportional to the administered rIL-2 dose, as was the rebound lymphocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL 2R(p55). Most CD3+ T cells were IL-2R(p55-,p75-). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+,CD3- NK cells among the lymphocytes had increased proportional to the administered rIL-2 dose. The levels of IL-2R(p75) expression by the CD56+,CD3- NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55), HLA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 x 10(6) U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinophil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+,CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment. PMID- 8485907 TI - Isotype-specific cross-linking of select human Fc gamma R isoforms triggers release of IL-6. AB - Anti-CD3 MoAbs are widely used in T cell activation studies, and are effective in immunosuppressive therapy. We used a panel of mouse (m) anti-CD3 switch variant MoAbs of five different isotypes to study IL-6 release from accessory cells. Incubation of human (h) mononuclear cells with anti-CD3 MoAbs resulted in increased IL-6 levels with MoAbs of mIgG1 and mIgG2a isotypes, with no effect of mIgG2b or mIgA. This suggested involvement of IgG Fc receptors (Fc gamma R) in triggering IL-6 production. To evaluate the role of different Fc gamma R molecules individually we used a panel of hFc gamma R-transfected mouse fibroblasts, and Jurkat T cells as a model. IL-6 secretion by CD32 transfectants expressing the hFc gamma RIIa high-responder (HR) allelic form was triggered by mIgG1 anti-CD3 MoAb, with no effect of four other isotypes. None of the anti-CD3 MoAbs induced IL-6 secretion by CD32 transfectants expressing either a variant of this receptor, containing only a single intracellular amino acid (CT-), the hFc gamma RIIa low-responder (LR) allelic form, or hFc gamma RIIb1. hFc gamma RI (CD64) transfectants exhibited IL-6 production after incubation with mIgG2a anti CD3 MoAb, and to a lesser extent with mIgG2b, and mIgG1 MoAb. Indirect involvement of T cells in triggering IL-6 secretion could be excluded by experiments in which transfectants were cultured with immobilized anti-CD3 MoAb. These data indicate that cross-linking of either hFc gamma RI, or hFc gamma RIIaHR by appropriate anti-CD3 MoAbs triggers IL-6 production of accessory cells, and not T cells. This may also take place in vivo during immunosuppressive therapy with anti-CD3 MoAbs, and related antibody-mediated immune responses. PMID- 8485908 TI - The anti-lipid A antibody HA-1A binds to rough gram-negative bacteria, fixes complement and facilitates binding to erythrocyte CR1 (CD35). AB - MoAbs to bacterial cell wall lipopolysaccharide are currently under evaluation for the treatment of Gram-negative sepsis. The mode of action of these reagents remains poorly understood. In this study we examined the ability of radiolabelled HA-1A (an IgM anti-lipid A MoAb) to bind in vitro to Salmonella minnesota (Re 595), Escherichia coli, and Streptococcus pyogenes. HA-1A was able to bind specifically to the 'rough' mutant Salm. minnesota, but not to a 'smooth' E. coli, or Strep. pyogenes. Binding to Salm. minnesota led to complement fixation which resulted in bacterial adherence to erythrocyte CR1, suggesting a possible mechanism whereby the antibody might enhance clearance of bacteria by facilitating delivery to the fixed mononuclear phagocytic system. We were not able to demonstrate the formation of immune complexes between free lipopolysaccharide and HA-1A in the presence of serum, nor the enhancement of complement-mediated binding of HA-1A:Salm. minnesota immune complexes to erythrocytes by antibiotic treatment. Binding of HA-1A to small bacterial fragments was, however, demonstrable after in vitro treatment with a beta-lactam antibiotic, which disrupts the bacterial cell wall, but not with gentamicin, an aminoglycoside antibiotic which blocks protein synthesis. PMID- 8485910 TI - Synovial fluid antigen-presenting cell function in rheumatoid arthritis. AB - We have previously demonstrated enhanced synovial fluid (SF) antigen-presenting cell (APC) function in inflammatory arthritis patients selected on the basis of marked SF mononuclear cell (MNC) responsiveness to reactive arthritis-associated bacteria (Clin Exp Immunol 1990; 79:189-94). In this study we have assessed whether similarly enhanced synovial APC function is present in other inflammatory arthritis patients by using two assay systems to study 18 rheumatoid arthritis patients whose MNC responsiveness had not been determined in advance. We demonstrate that rheumatoid SF APC are much more potent than peripheral blood (PB) APC in stimulating the responses of autologous PB T cells to a range of recall antigens. In addition, SF APC are shown to be efficient stimulators of the antigen-specific responses of MHC-compatible, cloned T cells. Enhanced synovial APC function is thus likely to be a general feature of inflammatory arthritis and may play an important role in its pathogenesis. PMID- 8485909 TI - Increased IL-6 gene expression and production in patients with common variable immunodeficiency. AB - We have studied IL-6 gene expression and production by in vitro stimulated peripheral blood mononuclear cells (PBMC) isolated from common variable immunodeficiency (CVI) patients. A strong hybridization signal for the IL-6 probe was observed in mRNA extracted from phytohaemagglutinin (PHA)- and PHA/phorbol myristate acetate (PMA)-stimulated PBMC from most of 12 CVI patients analysed. IL 6 production by PHA-stimulated PBMC from 28 CVI patients was evaluated in ELISA and found to be significantly (P < 0.0001) higher than in normal controls. IL-6 production, however, did not correlate with the lymphocyte populations examined, nor with the absolute number of monocytes. We have also showed that IL-6 was able to increase IgM secretion by several Epstein-Barr virus (EBV)-transformed cell lines derived from both normal donors and CVI patients, but it failed to modify substantially the amounts of IgM and IgG produced in vitro by PBMC derived from CVI patients and activated with pokeweed mitogen (PWM) or anti-IgM. Our data indicate that IL-6 gene expression and production is increased in CVI, but CVI cells do not respond to IL-6 with increased production of immunoglobulin. PMID- 8485911 TI - Increased epithelial expression of HLA-DQ and HLA-DP molecules in salivary glands from patients with Sjogren's syndrome compared with obstructive sialadenitis. AB - Salivary gland specimens from 10 patients with primary Sjogren's syndrome (pSS) were examined by two-colour immunofluorescence with various combinations of monoclonal and polyclonal antibody reagents of the following specificities: human leucocyte antigen (HLA) class I and II (DR, DP and DQ), CD3, CD45 (leucocyte common antigen), various cytokeratins, and factor VIII-related antigen. Tissue specimens from 10 normal glands and 10 glands with obstructive sialadenitis (no known autoimmunity) served as controls. Only some intercalated ducts and scattered acini of the normal major glands expressed HLA class II determinants (< 5% of total epithelial area); the relative proportion of positive elements indicated differential expression (DR > DP > DQ). SS glands contained substantial T cell infiltrates and increased numbers of activated (DR+) T cells; adjacent epithelium showed extensive differential expression of HLA class II determinants (DR > DP > DQ). Glands with obstructive sialadenitis showed similarly increased epithelial expression of HLA-DR but with surprisingly small amounts of concomitant HLA-DP and -DQ expression. Epithelial HLA class II expression probably depends on cytokines as an inductive event, which is not unique for SS but particularly prominent in this disorder. Our results suggest that epithelial expression of HLA-DP or -DQ, rather than -DR, might be a prerequisite for the autoimmune process of SS to develop in genetically susceptible individuals. PMID- 8485912 TI - C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE). AB - C1 inhibitor (C1-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. C1-inh antigenic levels were normal in all patients; however, the function of the C1-inh tested against C1s and C1r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients' C1-inh protein was 105 kD, corresponding to the size of the intact molecule. The C1-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major C1-inh gene rearrangement. Direct genomic sequencing of exon VIII revealed three polymorphic point mutations, but there were no changes from the normal gene in or around the reactive-centre residue of C1-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal C1-inh function in vitro. These results indicate that the etiology of C1-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema. PMID- 8485913 TI - Local and systemic activation of the whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers. AB - We have studied complement activation both in plasma samples and in lesional skin from patients with leukocytoclastic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers, C3d,g and the terminal complement complex (TCC) in plasma, showed that their levels were significantly increased in 66% and 55% of the patients, respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, C1q, C4 and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were significantly correlated. Importantly, a significant correlation was found between the severity of the vasculitis and both C3d,g and TCC plasma levels. Immunofluorescence studies of skin biopsy specimens demonstrated simultaneous presence of perivascular dermal deposits of C3d,g and TCC in lesional skin from 96% and 80% respectively of the patients (n = 25). There was a significant correlation between the intensity of the deposits of both markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits. Immunofluorescence studies at the epidermal basement membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presence of both C3d,g and clusterin-associated TCC perivascular deposits suggests an intervention of a regulatory mechanism of local complement activation in LCV. Finally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV. PMID- 8485914 TI - Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy. AB - A considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between the MHC class III complement proteins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis of the C4A and C4B isotype ratio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5.3 compared with LL patients without C4B*Q0. Since immune complexes (IC) are considered to be the pathogenic cause of ENL, our findings indicate that C4B deficiency may play an important role in the abnormal immune response against Mycobacterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals with this allele seem to be at a higher risk of developing pathological immune reactivity in lepromatous leprosy. PMID- 8485915 TI - Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes. AB - Endocrine autoimmune disorders are mediated by T cell-dependent responses to organ-specific antigens, but the mechanisms initiating the process remain unknown. Lymphocytes which use the gamma delta heterodimer as T cell receptor (TCR) for antigen constitute a distinct subset of T cells whose function remains elusive. In order to investigate their possible involvement in endocrine autoimmunity we have determined the proportion of gamma delta T cells in the peripheral blood of 23 patients with type 1 (insulin-dependent) diabetes mellitus (type-1 DM) and 30 patients with autoimmune thyrotoxicosis (Graves' disease). T lymphocyte TCR expression was assessed by fluorescence-activated flow cytometry on peripheral blood mononuclear cells using MoAbs UCHT1 (CD3), TCR delta 1 (gamma delta TCR), WT31 and beta F1 (alpha beta TCR) and both the percentage of T cells expressing gamma delta and the ratio gamma delta/alpha beta were calculated. In the diabetic patients gamma delta cells were not significantly different from the control group (7.7 +/- 54% versus 8.0 +/- 5.5% of T cells, P NS). There was no relation between the proportion of gamma delta lymphocytes and the presence of islet cell antibodies (ICA) in the sera. The Graves' patients showed a tendency towards a higher proportion of gamma delta T lymphocytes than the controls (gamma delta/alpha beta ratios: 0.095 +/- 0.047 versus 0.063 +/- 0.022, P = 0.03). In 14 Graves' patients the number of gamma delta were measured in paired samples of peripheral and intrathyroidal lymphocytes, demonstrating an expansion of gamma delta within the thyroid glands (0.21 +/- 0.3 versus 0.095 +/- 0.047, P = 0.032). Immunohistochemical studies showed that gamma delta cells were scattered among the predominant alpha beta lymphocytes infiltrating the thyroid gland and that they account for 10% of intraepithelial lymphocytes. No relation was found between the increase of gamma delta lymphocytes and any clinical features. PMID- 8485916 TI - Lymphoid cells in afferent and efferent intestinal lymph: lymphocyte subpopulations and cell migration. AB - Gut wall emigrating cells have been characterized in the intestinal lymph. The intestinal lymph duct was cannulated in 6-month-old minipigs. Under non restraining conditions the efferent lymph from the mesenteric lymph nodes was collected in seven normal animals. Lymph coming directly from the gut (afferent lymph) was also collected in 18 pigs after resection of the mesenteric lymph node chains 3 months previously. The intestinal lymph flow was similar in both groups (around 18 ml/h). The lymphoid cell yield was 1.2 +/- 1.0 x 10(6)/h in control animals, while in mesenteric lymph node resected pigs it was around 20 times higher (26.2 +/- 17.6 x 10(6)/h). In the gut-derived lymph 76.5 +/- 8.8% T lymphocytes were observed (CD4+, 48.1 +/- 15.5%; CD8+, 53.6 +/- 12.7%). The percentage of immunoglobulin-positive cells was lower (IgM+, 10.1 +/- 4.5; IgA+, 1.7 +/- 1.1). In 14 mesenteric lymph node resected pigs a mean of 5.6 +/- 3.1 x 10(8) lymphocytes from the gut lymph were labelled in vitro with a fluorescent dye and retransfused. The labelling index of fluorescent cells in the intestinal lymph increased rapidly and remained at a high level until 44 h after cell transfusion. A four-to-ten times lower labelling index was found in the spleen, various lymph nodes and Peyer's patches. Most of the recovered lymphocytes were T cells. This model provides access to the cell pool leaving the gut wall, thus allowing an examination of its role in the gastrointestinal tract and other mucosal-lined organs. PMID- 8485917 TI - Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma. AB - We have tested the effect of administering H22, a hamster neutralizing MoAb to murine interferon-gamma (IFN-gamma) in collagen-induced arthritis. Mice were immunized with human type II collagen in adjuvant on day 1 and boosted with soluble collagen on day 21. H22 was administered (250 micrograms, intraperitoneally) either during the induction of arthritis (on days 0, 6, 13 and 20) or around the time of disease manifestation (on days 21, 28, 35 and 42). Control mice received either an isotype-matched non-neutralizing MoAb or saline. Both treatment regimes gave similar results. Treatment with H22 did not significantly affect the incidence of arthritis, time of onset, degree of oedema, histopathological severity, or level of anti-type II collagen IgG. However, a highly significant increase (P < 0.01) in the number of limbs affected by arthritis was observed in the H22-treated group, irrespective of whether the antibody was administered during the induction of arthritis, or during the time of clinical manifestation of disease. From these results it was concluded that anti-IFN-gamma treatment caused an increase in the number of arthritic lesions, but did not affect the severity of each individual lesion. PMID- 8485918 TI - Trafficking of inflammatory macrophages from the kidney to draining lymph nodes during experimental glomerulonephritis. AB - Macrophage accumulation within the glomerulus and renal interstitium is a prominent feature of most forms of glomerulonephritis, but the fate of these inflammatory cells is unknown. Macrophage trafficking to the draining kidney lymph nodes (KLN) was assessed in a detailed kinetic analysis of accelerated antiglomerular basement membrane (GBM) disease in the rat. Leucocytes draining to KLN via lymphatic vessels were identified within the marginal sinus by MoAb labelling of tissue sections. In anti-GBM disease, there was a significant increase in the weight of the KLN due to both lymphoproliferation within the nodes and increased lymphatic drainage from the inflamed kidney, as evidenced by prominent dilation of the marginal sinus and increased numbers of cells within the sinus. In non-inflamed lymph nodes, few ED1+ macrophages were present within the marginal sinus (3.0 +/- 0.6/100 nucleated cells). However, in anti-GBM disease, macrophages became the major cell type within the dilated marginal sinus of the KLN, as shown by labelling with ED1, ED2 and ED3 MoAbs, peaking at 74 +/- 2.6 ED1+ cells/100 nucleated cells at day 14. These changes were not simply due to systemic antigen administration, since in the axillary lymph node (ALN) there was no obvious dilation of the marginal sinus and macrophages accounted for a maximum of only 15 +/- 4.6 ED1+ cells/100 nucleated cells. In conclusion, this study provides indirect evidence that there is significant trafficking of the renal macrophage infiltrate to the KLN during experimental glomerulonephritis. This may be a mechanism whereby nephritogenic antigens, released as a consequence of the local inflammatory response, may be presented to T and B lymphocytes within lymph nodes, resulting in the amplification of the immune response in glomerulonephritis. PMID- 8485919 TI - Quantitative study of mesangial injury with proteinuria induced by monoclonal antibody 1-22-3. AB - Murine MoAb 1-22-3 has already been reported to bind to the mesangial cell surface and to cause transient proteinuria and mesangial morphological changes characterized by mesangiolysis, subsequent mesangial cell proliferation and mesangial matrix increase by a single i.v. injection. In this study, MoAb-induced glomerulopathy was quantitatively analysed. No correlation between the severity of mesangial morphological changes and the degree of proteinuria was detected (r = 0.190). The minimum dose injected to induce abnormal proteinuria was 25 micrograms. This dose corresponded to 1.79 micrograms/2 kidneys 30 min after MoAb injection. The highest average level of proteinuria was observed in rats injected with 500 micrograms of MoAb, and less proteinuria was observed in rats injected with 10.0, 5.0 and 2.0 mg. Although the amounts of kidney-fixing MoAb and the subsequent deposition of rat C3 in the high-dose-injected group were larger than in the 500 micrograms injected group, the numbers of infiltrating inflammatory cells were the same in both groups. No correlations between the degrees of such mediators and proteinuria were observed. PMID- 8485920 TI - Investigation of class I anti-arrhythmic drug actions on guinea-pig cardiac mitochondrial lactate dehydrogenase activity. AB - 1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration-dependent fashion, exhibiting varying profiles in their actions. Lidocaine exhibited inhibitory concentration 20% (IC20) and IC50 values of 0.52 +/- 0.02 mmol/L and 25.6 +/- 0.5 mmol/L, procainamide 6.0 +/- 0.2 mmol/L and 108 +/- 7.2 mmol/L, phenytoin 3.4 +/- 0.06 mumol/L and 0.34 +/- 0.02 mmol/L, quinidine 39.2 +/- 1.2 mumol/L and 9.8 +/- 0.8 mmol/L and tocainide 2.7 +/- 0.3 mmol/L and 44.6 +/- 2.5 mmol/L. 3. According to the IC50 values, this is the order of their inhibitory potencies: phenytoin > quinidine > lidocaine > tocainide > procainamide. This trend is in general agreement with the lipophilicity rank of the drugs. 4. It is concluded, therefore, that inhibition of mitochondrial lactate dehydrogenase is a property shared by most Class I anti-arrhythmic drugs which may depend on their lipophilicity and possibly their membrane stabilizing effects. PMID- 8485921 TI - Effects of aldose reductase inhibition with epalrestat on diabetes-induced changes in rat isolated atria. AB - 1. Isoprenaline and cardiac responsiveness of isolated atria from 2 and 6 week streptozotocin-diabetic rats, and their age-matched controls, was examined. The effects of chronic administration of epalrestat (40 mg/kg orally, by gavage) on diabetes-induced changes were also investigated. 2. Spontaneously beating atria, bathed in either normal or high glucose (30 mmol/L) Krebs' solution, from both 2 and 6 week diabetic rats beat more slowly and with greater force than atria from control rats. These changes in basal parameters were normalized by 2 weeks of insulin (5 U/day s.c.) treatment but not by 2 or 6 weeks of chronic treatment with epalrestat. 3. Isoprenaline (0.1 nmol-0.1 mumol/L) produced concentration dependent increases in inotropy and chronotropy in atria from both control and diabetic rats. 4. Atria from 2 week diabetic rats displayed decreased sensitivity to the positive inotropic effects of isoprenaline. This change was normalized by chronic insulin treatment but not by chronic epalrestat treatment. 5. Atria from 6 week diabetic rats displayed increased sensitivity to the positive chronotropic effects of isoprenaline which was normalized by epalrestat. 6. These results suggest that changes observed in atria from 2 week diabetic rats may be due to hyperglycaemia per se whereas in atria from 6 week diabetic rats abnormal activity of the polyol pathway may be a contributing factor. PMID- 8485922 TI - The effect of cromakalim on the electrical properties of and [86Rb+] efflux from normal and hypertrophied rat bladder. AB - 1. The activity of smooth muscle strips from normal and hypertrophied rat bladders was compared. The hypertrophied bladders were produced by partially obstructing the urethra 8-13 weeks previously. 2. Spontaneous mechanical activity was more frequent and smaller in amplitude in strips from normal than hypertrophied bladders and was less sensitive to cromakalim, being reversibly abolished by cromakalim at 10(-6) mol/L compared with 10(-7) mol/lL for hypertrophied bladder. 3. The mean resting membrane potentials of smooth muscle cells from normal and hypertrophied rat bladders were -47.2 and -47.6 mV, respectively. Bursts of spontaneous action potentials, corresponding to the mechanical activity, were seen in some cells. 4. Nifedipine at 10(-6) mol/L had no significant effect on the resting membrane potential. Occasional single spikes occurred with increased duration and the after hyperpolarization was abolished. Cromakalim at 10(-5) mol/L produced hyperpolarization of 3-9 mV and, in the continued presence of the drug, occasional singe spikes could be recorded from both normal and hypertrophied bladders. 5. Nifedipine at 10(-6) mol/L abolished movement but did not significantly alter [86Rb+] efflux from strips from either normal or hypertrophied bladders. Addition of cromakalim at 5 x 10(-6) or 5 x 10( 5) mol/L in the presence or absence of nifedipine increased efflux from the normal bladder by 30-40%. In the hypertrophied bladder the efflux increased by about 14% and 28% in the presence of 5 x 10(-6) and 5 x 10(-5) mol/L cromakalim, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485923 TI - Identification and characterization of an amidating enzyme in ovine heart. AB - 1. Levels of peptidylglycine alpha-amidating mono-oxygenase (PAM) activity were examined in sheep and rat heart. This enzyme is responsible for alpha-amidation of a large number of peptide hormones, a modification essential for the bioactivity of these peptides. 2. PAM activity was measured in membrane and soluble fractions of atrial and ventricular homogenates by monitoring the amidation of iodinated synthetic substrate ([125I]-Ac-Tyr-Val-Gly). 3. PAM activity in both species resided almost exclusively in the atria rather than the ventricles, and similar levels of activity were found in left and right atria. Membrane-associated activity was 50-to 100-fold greater than soluble activity in the sheep, yet was only five- to 10-fold greater in the rat, indicating a larger proportion of soluble enzyme in the rat atrium. 4. Similar apparent Km values were found for atrial membrane-associated activity in both species (15.6 and 17.4 mumol/L for rat right and left atria, 16.7 and 15.6 mumol/L for sheep right and left atria); however, the maximum velocity (Vmax) levels were higher in the rat (40.5 and 43.9 pmol/micrograms per h vs 12.8 and 15.1 pmol/micrograms per h). 5. Because expression of many peptides and processing enzymes can be regulated by steroid hormones, the possible effects of chronic glucocorticoid administration (1 mg dexamethasone i.m. twice daily for 10 days) on PAM levels were tested in four sheep, with four sheep receiving saline only as controls. There was no discernible effect of dexamethasone on either the distribution or the kinetics of PAM activity in the sheep heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485924 TI - The effect of atrial natriuretic peptide infusion on renal haemodynamics and plasma lipoproteins in puromycin aminonucleoside nephrosis in rats. AB - 1. The effect of continuous intravenous administration of 1 microgram/h atrial natriuretic peptide (ANP) for 4 days was studied in normal male Sprague-Dawley rats and rats made nephrotic with puromycin aminonucleoside (PA). 2. ANP infusion significantly increased urinary sodium and potassium excretion by 3 days of infusion in control rats but not in PA-treated rats. ANP infusion significantly increased glomerular filtration rate in PA-treated rats, while effective renal plasma flow was similarly decreased compared with non-infused nephrotic rats. 3. Plasma high density lipoproteins (HDL) were significantly decreased and low density lipoproteins (LDL) were increased in PA-treated rats that received ANP; HDL were increased in normal rats infused with ANP. 4. Competitive binding studies demonstrated a lower density of specific ANP receptors in glomerular membranes from rats injected with PA, while binding affinity was unchanged. 5. Infusion with exogenous ANP did not promote natriuresis in PA nephrosis despite an enhancement of glomerular filtration rate (GFR), thus suggesting that sodium retention in this model is due to a post-glomerular defect. Plasma lipoprotein composition in both normal and nephrotic rats may be affected by ANP. PMID- 8485925 TI - Angiotensin converting enzyme inhibitor, captopril, inhibits cardiac hypertrophy without changing collagen types and concentration in spontaneously hypertensive rats. AB - 1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non-interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). These parameters were examined in age and sex matched Wistar-Kyoto (WKY) rats, as well as in non-treated SHR, and compared with those of captopril-treated SHR. 2. Captopril significantly reduced both blood pressure (191 +/- 12.1 vs 146 +/- 11.2 mmHg, P < 0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 +/- 0.17 vs 2.05 +/- 0.12 mg/g, P < 0.01). There were no significant differences in collagen concentration among WKY rats, captopril-treated SHR and non-treated 32 week old SHR. However, total collagen content in captopril-treated SHR reduced significantly compared with non-treated 32 week old SHR (16.8 +/- 2.0 vs 21.3 +/- 0.8 mg, P < 0.01). The relative proportion of type V collagen was significantly higher in both captopril-treated (58.6 +/- 3.4 vs 46.8 +/- 1.3%, P < 0.01) and non-treated 32 week old SHR (59.9 +/- 3.1 vs 46.8 +/- 1.3%, P < 0.01) compared with WKY rats. However, there were no significant differences between captopril-treated SHR and non-treated 32 week old SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485926 TI - Effects of reserpine on the content and uptake of dopamine and noradrenaline in rabbit arteries. AB - 1. Change with time of the content and uptake of dopamine (DA) and noradrenaline (NA) in the renal, superior mesenteric and femoral arteries and abdominal aorta of rabbit after reserpine administration was examined. Endogenous DA and NA were measured by high performance liquid chromatography coupled with electrochemical detector. 2. A single dose of reserpine (3 mg/kg, i.p.) maximally depleted the endogenous DA and NA contents in the four blood vessels 24 h after the administration; the ratios of reductions were 70-90% and approximately 90% of the normal levels, respectively. The DA contents in all four vessels recovered to the normal level within 4 days after reserpine. However, NA content did not recover to the normal levels within 30 days after reserpine except in the mesenteric artery. 3. The activity of dopamine beta-hydroxylase (DBH) significantly increased in all four blood vessels 1 h after reserpine. Although the DBH activity returned to the normal level after 3 days in the mesenteric artery, it returned within 24 h in the other three vessels. 4. [3H]-Dopamine and [3H]-NA uptake were almost completely depressed 1 h after reserpine. The [3H]-NA uptake in four vessels recovered to the normal level 2-14 days after reserpine, and [3H] DA uptake recovered after 30-45 days. Thus, the endogenous DA content in blood vessels was completely restored although DA uptake and NA content were still affected. 5. These results suggested that the recovery of stored DA after reserpine was faster than that of stored NA and the recovery of DA uptake after reserpine was slower than NA uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485927 TI - Oxygen-haemoglobin dissociation curve in hypoxic rats of first or second generation. AB - 1. Albino Wistar rats were raised in a normobaric hypoxic environment (10% O2 in N2). Two generations of hypoxic rats were observed for changes in their haemoglobin-oxygen (Hb-O2) dissociation curves (ODC), 2,3-diphosphoglycerate (2,3 DPG), haemoglobin (Hb), and Hill co-efficients at P50 (n50). The first generation were called (H1) and the second generation (H2). The control group (N) had a normoxic environment. 2. Thirty-five rats (13 N rats, 12 H1 rats and 10 H2 rats) were used. The 2,3-DPG was significantly higher in both hypoxic groups when compared with N rats (2.02 +/- 0.51 mmol/L) but 2,3-DPG of H2 rats was significantly lower than that of H1 rats (H1 = 3.48 +/- 0.58 mmol/L and H2 = 2.76 +/- 0.54 mmol/L). The haemoglobin values were N = 2.00 +/- 0.26, H1 = 2.65 +/- 0.32 and H2 = 2.36 +/- 0.30 mmol/L, respectively. 3. We observed considerable differences in Hb-O2 affinity between the three groups of rats. In standard conditions (pH = 7.400; pCO2 = 40 mmHg at 37 degrees C) the H1 rats showed a significantly decreased Hb-O2 affinity (P50,st = 37.0 +/- 1.3 mmHg) when compared with both H2 and N rats; the H2 rats showed a significantly increased Hb-O2 affinity (P50,st = 31.1 +/- 1.5 mmHg) when compared with controls N (P50,st = 34.7 +/- 2.1 mmHg). There were no significant differences in n50 values: N = 2.88 +/- 0.44; H1 = 2.88 +/- 0.77; and H2 = 2.94 +/- 0.67.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8485928 TI - Respiration and BP and HR variability. PMID- 8485929 TI - Upper blepharoplasty by eyelid invagination. Anchor blepharoplasty. AB - Anchor or lid invagination blepharoplasty is an operation giving neat, crisp, and youthful lids of a permanency unobtainable by traditional techniques. It allows the surgeon to preserve precious lid skin and give optimal results. Although there is more postoperative edema, long-term results verify the efficacy of the technique. This article represents the author's 25 years' experience with thousands of patients, both Caucasians and Orientals, undergoing invagination technique lid blepharoplasty procedures. PMID- 8485930 TI - Essential anatomy for contemporary upper lid blepharoplasty. AB - A clear understanding of upper eyelid anatomy is an absolute prerequisite for performing advanced invagination-type blepharoplasty. This article describes the author's simple, systematic approach to intraoperative identification of the levator aponeurosis as well as the other key layers of fascia in the upper lid. PMID- 8485931 TI - Preoperative evaluation of the blepharoplasty patient. Bypassing the pitfalls. AB - Patients predisposed to postoperative eyelid malposition can be identified by the careful preoperative analysis of the periorbital anatomy in conjunction with a good medical history. When necessary, ancillary procedures are performed at the time of the initial blepharoplasty to avoid undesirable deformities. PMID- 8485932 TI - Contemporary upper lid blepharoplasty--tissue invagination. AB - Blepharoplasty is the most commonly performed operation to enhance facial appearance. Controversy arises over the need for tissue invagination as opposed to simple tissue excision. This article focuses on advanced invagination-type blepharoplasty, discussing who, what, where, when, why, and how. PMID- 8485933 TI - The East Asian eyelid-open technique. AB - Creation of a dynamic levator aponeurosis fold or double eye adds to the beauty of the East Asian. The eyes are larger and less puffy, and the eyelashes appear longer and curve up and out instead of down. The distance from the ciliary border to the eyebrow is decreased and more in proportion. The Mongolian trait is preserved. PMID- 8485934 TI - The biomechanics of brow and frontalis function and its effect on blepharoplasty. AB - Understanding the biomechanics and dynamics of eyebrow and frontalis function is essential to controlling the outcome of blepharoplasty. Ignoring the forehead in the pursuit of blepharoplasty excellence dooms to failure any eventual outcome. If, however, the principles laid out in this article become the basis for planning and execution, the final result, measured in the quality of aesthetic repair, will surely improve immensely. PMID- 8485935 TI - Ptosis repair in aesthetic blepharoplasty. AB - It is important to recognize ptosis of the upper eyelids in patients who are contemplating aesthetic blepharoplasty. When ptosis is present, it should be corrected simultaneously with the blepharoplasty. PMID- 8485936 TI - Blepharoplasty in the patient with exophthalmos. AB - The plastic surgeon performing blepharoplasty should maintain a high degree of surveillance for the presence of exophthalmos. Exophthalmos may be masked by the presence of eyelid compensations and substantial amounts of eyelid fat. The surgeon should know how to detect the condition and measure its extent. PMID- 8485937 TI - Treatment of exophthalmos by orbital fat removal. AB - Decompression of the orbit by removal of fat is a safe method to obtain functional and aesthetic improvement in exophthalmos disease. In comparison with traditional orbital wall decompression, the complication rate is low. PMID- 8485938 TI - Periorbital appearance as a function of orbital volume. PMID- 8485939 TI - Surgical correction of the crow's feet deformity. AB - Improved methods and important adjuncts for rejuvenation of the aging face have evolved as surgeons have recognized the limitations of the techniques they employ. Presented here is a simple, safe, and straightforward technique for correction of the "crow's feet" deformity that has proven to produce a predictable and long-lasting improvement. PMID- 8485940 TI - Precision planning in blepharoplasty. The importance of preoperative mapping. AB - Routine standardized periorbital planning prior to blepharoplasty and brow lifting facilitates optimal outcome and minimizes the need for reoperation. It should be an essential companion to blepharoplasty in all instances. PMID- 8485941 TI - Updated muscle suspension and lower blepharoplasty. AB - The challenge of lower lid blepharoplasty surgery is to get the lid tight enough to smooth out wrinkles and not produce scleral show or round eye. The updated lower lid muscle suspension blepharoplasty can meet this challenge. The technique uses an easily placed muscle suspension suture to help support or elevate the lower lid. PMID- 8485942 TI - Minimizing deformity in lower blepharoplasty. The transconjunctival approach. AB - The transconjunctival approach offers many advantages for lower blepharoplasty. It addresses bulging fat directly, minimizes late lid retraction problems, permits skin resection if indicated, and retains the natural appearance of the palpebral fissure. The technique is straightforward and is easily mastered once the relevant anatomy is understood. PMID- 8485943 TI - Herniated fat and the orbital septum of the lower lid. AB - The bulging fat of aging eyelids has always been described as a hernia; yet, the treatment has not been that of a true hernia. Rather, the contents (orbital fat) have been excised and the hernia wall left unrepaired. It is possible to treat bulging lower eyelids as a hernia by replacing both the fat and the sac into the original location within the orbital cavity, and then repairing the retaining wall. PMID- 8485944 TI - Correction of weakness of the lower eyelid and lateral canthus. Personal techniques. AB - The author describes the approach to weakness of the lower eyelid and lateral canthus due to a decreased tension of the orbicularis muscle and canthal ligament. He describes several techniques such as blepharocanthoplasty, muscular suspension blepharoplasty, submusculoaponeurotic system rhytidectomy of the upper two thirds of the face, and a temporal fascia sling procedure indicated for major elevation of the lower eyelid and rim. PMID- 8485945 TI - Canthopexy as a routine blepharoplasty component. AB - Canthopexy should be a routine companion or alternative to lower lid blepharoplasty. It restores tone and youthful contour to the deteriorating eye, and it reduces or eliminates the need to resect skin that in truth is not excessive, but appears so owing to dropped lid posture from lid atonicity. Canthopexy with fat reduction and enhancement of the deficient suborbital portion of the malar complex should be the principal thrust of lower lid surgery. Skin removal accompanies this only when there is true excess and redundancy. Transconjunctival or stab wound fat removal are preferred procedures when there is no excess skin to remove. Canthopexies are possible through lower lid incisions, through upper lid incisions, or via coronal type access. They are an essential companion to aesthetic blepharoplasty if the surgeon wishes to prevent deformity. PMID- 8485946 TI - Festoons, mounds, and bags of the eyelids and cheek. AB - This article categorizes and defines periorbital soft tissue protrusions associated with aging. (Protrusions of intraorbital fat are excluded. Recent anatomic observations are described as well as surgical procedures based on these findings and on past experience. Complications are enumerated and their treatment is outlined. PMID- 8485947 TI - Diagnosing photographic distortion. Decoding true postoperative contour after eyelid surgery. AB - A method of "decoding" deceptive blepharoplasty photographs resulting from head postural changes (or changes in camera planes) between pre- and postoperative photographs is now available. One need only measure changes in the intercanthal axis relative to the horizontal plane of the face. Each degree of alteration of the axis represents 1 mm of true postural change in the margin of the lower lid- disguised by head tilt or downward gaze. This new "tool" can expose and help eliminate undesirable techniques that consistently deform the eye through lowered lid posture and increased scleral show, saddening the appearance of the orbital region and the entire face. PMID- 8485948 TI - Naso-jugal groove leveling with fat tissue. AB - One of the causes of a depressed naso-jugal groove is the fixation of the septum orbitale at the level of the inferior-medial portion of the arcus marginalis. To permit the leveling of the groove, it is necessary to liberate the subjacent orbital septum from its fixation to the arcus marginalis. To avoid recurrence of the depression, some fat tissue is properly placed in the undermined space subjacent to the groove. This can be done by free fat grafting or fat pad sliding. PMID- 8485949 TI - Tear trough implants for correction of tear trough deformity. AB - This essay describes the tear trough deformity and its extension into the cheek. It is an extremely common and consistently deforming characteristic of the lower orbital region. The article focuses on cause and correction. A suborbital malar implant designed to alleviate the deformity is now available from an implant manufacturer in a variety of sizes. The procedure provides in most instances a definitive correction of a significant disfigurement. PMID- 8485950 TI - Repair of lower lid deformities. AB - The most common complication of blepharoplasty is an unnatural distortion of the lower eyelid. Identification of the underlying anatomic deformities dictates the reconstructive procedures. Emphasis is placed on utilization of the dermal orbicular pennant lateral canthoplasty. PMID- 8485951 TI - Compiling a district diabetic register: theoretical and practical considerations. PMID- 8485952 TI - The skin in diabetes. PMID- 8485953 TI - Aldose reductase inhibitors and the complications of diabetes mellitus. PMID- 8485954 TI - Frequency and symptoms of hypoglycaemia experienced by patients with type 2 diabetes treated with insulin. AB - This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1-17) years (median (range)) vs partial awareness: 9 (3-18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2-25) years vs partial awareness: 19 (8-24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1-18) years vs partial awareness: 12 (6-17) years, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485955 TI - Frequency and morbidity of severe hypoglycaemia in insulin-treated diabetic patients. AB - To estimate the frequency and morbidity of insulin-induced hypoglycaemia, a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 randomly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital. The resulting morbidity (hypoglycaemia-related injuries, convulsions, and road traffic accidents) was ascertained in 302 patients. One hundred and seventy-five (29.2%) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year, giving an overall frequency for the group of 1.60 episodes patient-1year-1. The frequency of severe hypoglycaemia which was documented in 544 Type 1 (ketosis prone) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin (1.70 vs 0.73 episodes patient-1year-1). In the subset of 302 patients, those who had experienced severe hypoglycaemia had greater morbidity associated with an estimated rate of injury of 0.04 injuries person-1year-1. Twenty (6.6%) patients reported a total of 37 convulsions associated with hypoglycaemia, 5 of which had occurred in the preceding year (0.02 convulsions person-1year-1). Five patients reported road traffic accidents in the preceding year which had been caused by hypoglycaemia. The only reliable predictors of severe hypoglycaemia were a history of previous severe hypoglycaemia (p < 0.001), a history of hypoglycaemia related injury (p < 0.001) or convulsion (p < 0.001), and the duration of insulin therapy (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485956 TI - An analysis of the glucagon response to hypoglycaemia in patients with type 1 diabetes and in healthy subjects. AB - The study aimed to analyse the glucagon response during hypoglycaemia in relation to gender, level of hypoglycaemia, and hyperinsulinaemia as well as its relation to other counterregulatory hormones in patients with Type 1 diabetes and in nondiabetic subjects. Mild hypoglycaemia was induced by an i.v. insulin infusion (244 pmol kg-1h-1) for 180 min in 43 Type 1 diabetic patients and 22 nondiabetic subjects. Venous blood glucose, plasma free insulin, glucagon, adrenaline, noradrenaline, growth hormone, and cortisol were measured every 15-30 min. The hormonal responses during hypoglycaemia were evaluated from the incremental areas under their respective curves. There was a linear correlation between the glucagon response and the decremental area of blood glucose (p < 0.005), but the slope of the regression line in the diabetic group was less steep than in the controls (p < 0.5), and, in spite of the deeper hypoglycaemia in the diabetic groups, their glucagon response was diminished (p < 0.05). Plasma, adrenaline, growth hormone and cortisol all increased during hypoglycaemia. The glucagon response correlated with the responses of growth hormone and cortisol in both groups, while it was positively correlated with the adrenaline response (p < 0.001) and inversely with the plasma insulin (p < 0.001) only in the diabetic patients. Although the insulin infusion rate was identical, the female diabetic patients had a lower metabolic clearance rate of insulin as compared with the males (p < 0.05). There was no statistical difference in the counterregulatory hormone responses between males and females in neither of the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485957 TI - Sudden death and human insulin: is there a link? AB - Case reports from the United Kingdom (UK) in 1989 have suggested that the introduction of human insulin in 1985 was associated with an increased risk of sudden death in insulin-treated diabetic patients. If human insulin increases the risk of sudden death, the number of these should have increased during the period where human insulin was introduced. We therefore identified all cases of sudden death in Denmark in younger insulin-treated diabetic patients, age at death below 50 years. During this period the consumption of human insulin went from 0.2% to 70% of the total consumption in Denmark. The total number of cases fulfilling the inclusion criteria was 226, and the annual number of sudden deaths did not change during the study period (p = 0.14). The number of deaths due to hypoglycaemia and cases with unexplained cause of death also remained constant (test for trend: p = 0.44). Chronic alcohol abuse or acute alcohol intoxication was found in 50% of the 135 patients dying from hypoglycaemia, ketoacidosis or unknown cause of death (including found dead in bed), while this was the case in only 16% of the remaining 91 cases dying from other natural causes. We conclude that introduction of human insulin in Denmark was not followed by an increase in sudden deaths among younger insulin-treated diabetic patients. PMID- 8485958 TI - A novel device for the rapid in-clinic measurement of haemoglobin A1c. AB - In order to evaluate a novel technique for measuring haemoglobin A1c using a cassette-based immunoassay method we have undertaken a laboratory evaluation using 48 patient samples and a separate within-clinic prospective study of 59 diabetic patients. Individuals were recruited from general (48 patients), paediatric (19 patients), obstetric (24 patients), and general practice (15 patients) diabetic clinics. Agreement was evaluated between HbA1c results obtained using the new method (AMES DCA 2000) and an established laboratory assay (DIAMAT HPLC system). The mean differences between the two results (AMES DCA 2000 DIAMAT) (95% confidence intervals) were: laboratory -0.69% (-1.42 to 0.04%); paediatric clinic -0.93% (-1.93 to 0.07%); obstetric clinic -0.29% (-1.09 to 0.51%), and general practice clinic -0.77% (-1.3 to -0.24%). For the AMES DCA 2000, the coefficient of variation for HbA1c of 5.2% was 1.6% and for HbA1c of 13%, 2.4%. This instrument was used without difficulty by four different operators. Intra-assay coefficient of variation for each operator was < 3.4%. In 9/18 patients where a specific assessment of clinical utility was made, knowledge of the HbA1c result at the time of consultation lead to a change in treatment. Methodology of this type may be used successfully within a diabetic clinic setting in both primary care and hospital environments. PMID- 8485959 TI - Diabetes in the elderly: an under-diagnosed condition. AB - The proportion of the population aged 65 years and over is increasing. The Coventry Diabetes Study was able to investigate the prevalence of diagnosed and undiagnosed diabetes among elderly (aged > or = 65 years) Europeans (n = 1600) and South Asians (n = 288) in Foleshill, Coventry. The total prevalence of diabetes was higher in South Asians than Europeans among males (30.7 (95% CI 24.0 37.9)% vs 7.7 (95% CI 5.8-10.0)%, respectively) and females (24.0 (95% CI 17.5 32.4)% vs 12.5 (95% CI 10.6-14.8)%, respectively). The proportion with diagnosed diabetes was higher among South Asians than Europeans (55% vs 33%, p < 0.001), possibly because of their earlier onset. These findings suggest that detection of diabetes in elderly Europeans in urban areas may be inadequate. PMID- 8485960 TI - Outpatient treatment of unilateral diabetic foot ulcers with 'half shoes'. AB - The impact of 'half shoes' in the treatment of neuropathic forefoot ulcers was studied in two groups of diabetic patients, who were treated either by standard treatment alone (retrospective controls, n = 22), or by standard treatment plus 'half shoes' (cases, n = 26). The groups were matched for sex, age, type, and duration of diabetes and ulcer grading. The 'half-shoe' cases' vs controls' median overall healing time was 70 vs 118 days, the median difference being 48 (95% CI: -5 to 82) days (NS). In the case group, hospitalization was required in 1/26 (4%) of patients, vs 9/22 (41%) of the control patients (chi-square, p < 0.01). The home nursing service was required in 23% of the cases vs 18% of the controls (NS). It is concluded that the use of half-shoes, in conjunction with standard treatment provided by a specialized diabetic foot clinic, may reduce the overall healing time and does reduce the hospitalization rate. This has implications for a rational strategy of treating unilateral diabetic neuropathic foot ulcers. PMID- 8485961 TI - Ethnic differences in the incidence of lower extremity amputation secondary to diabetes mellitus. AB - Patients of Asian ethnic origin with diabetes mellitus living in the United Kingdom (UK) have been shown to have a higher prevalence of coronary heart disease and renal disease. Little is known about the incidence of lower extremity amputation in this racial group. The incidence of lower extremity amputation was estimated for patients of Asian ethnic origin and White Caucasians with diabetes mellitus in the county of Leicestershire from 1980 to 1985. The age and sex adjusted incidence rate of lower extremity amputation for the estimated population of patients with diabetes mellitus in patients of Asian ethnic origin was 3.4 (95% CI, 1.1-10.7) cases per 10,000 patients year-1, compared to 14.2 (12.6-15.9) in White Caucasians. Similarly, a lower incidence rate of lower extremity amputation was recorded in patients of Asian ethnic origin without diabetes mellitus (0.4 (0.2-0.6) vs 1.5 (1.4 to 1.6) cases per 10,000 persons year-1). These findings contrast markedly with the high rates of coronary heart disease and renal disease previously reported in patients of Asian ethnic origin residing in the UK. PMID- 8485962 TI - Smoking in diabetic teenagers. AB - The prevalence of smoking amongst a group of 77 diabetic teenagers aged 11-18 years attending two paediatric clinics was determined using a questionnaire and urine cotinine assay. Five individuals were identified as definite smokers with two further individuals being probable smokers, all of whom were aged 15 years or more. This low prevalence (9%) is in contrast to a 48% prevalence in a young adult diabetic clinic. Many diabetic teenagers appear to acquire a regular smoking habit after leaving the paediatric clinic so it is important that health education is targeted at this group. PMID- 8485963 TI - Persisting mortality in diabetic ketoacidosis. AB - An overall hospital mortality rate of 3.9% was found in 929 episodes of diabetic ketoacidosis treated in single centre over a 21-year period. The mortality rate in the first half of the survey (4.4%) was not significantly different from that in the second half of the survey (3.4%). Six deaths in patients under 50 years of age occurred in the first half, but only one death under 50 years occurred in the second half of the survey. The number of deaths from a metabolic cause where no other illness was identified also fell from nine (43% of deaths) in the first half to five (33% of deaths) in the second half of the study (not significant). The remaining deaths were due to concurrent illness, mainly myocardial infarction and serious infections. Many of the residual deaths occurred in elderly patients with such medical illness in addition to the ketoacidosis. It may, therefore, prove difficult to reduce mortality further in diabetic ketoacidosis. PMID- 8485964 TI - Coming of age with diabetes: patients' views of a clinic for under-25 year olds. AB - This study is both an evaluation of patients' perceptions of a diabetes clinic for under-25 year olds, and an assessment of experiences in transferring from a paediatric clinic. Sixty-nine patients with Type 1 diabetes (74% of the total clinic), including 41 females, completed evaluations of the clinic and recall of experiences in transfer. Mean age on transferring clinic was 15.9 (range 12-20) years. Paediatricians were perceived to emphasise family and social life, school or work progress; adult physicians tended to stress the risk of long-term complications, importance of exercise and need to maintain strict levels of glycaemic control. Our data suggest that transition to adult care can generally be achieved non-traumatically, but patients may perceive some difficulty because of different emphases and treatment advice favoured by paediatricians and adult physicians. PMID- 8485965 TI - Outcome of pregnancy in diabetic women in Soweto, South Africa 1983-1992. AB - A specialized service for pregnant diabetic women of African ethnic origin from Soweto was introduced in May 1983 at Baragwanath Hospital. Modern methods of management were used, including home blood glucose monitoring. A total of 354 pregnancies (147 gestational, 207 pregestational) were managed over an 8 1/2 year period. All but 12 women were treated with insulin. Mean capillary blood glucose (+/- SD) ranged from 5.8 +/- 0.8 mmol l-1 in the insulin-dependent group to 6.2 mmol l-1 in the gestational group (p < 0.01). Although maternal hypoglycaemia was common (14.4%) in the insulin-dependent patients, no ill effects were noted. The highest Caesarean section rate was in the gestational group (56%), the lowest in the insulin-dependent group (39.8%) (p < 0.01). Mean (+/- SD) neonatal weights were similar in the insulin-dependent and non-insulin-dependent groups (3131 +/- 627.9 g and 3236 +/- 674.3 g resp. p = NS); offspring of the gestational group were heavier than the insulin-dependent group (3384.4 +/- 657.5 g) (p < 0.01). Neonatal hypoglycaemia occurred in less than 5% of offspring overall. The combined perinatal mortality was 6.1%, stillbirths accounting for the majority (63.6%) of deaths. Major congenital abnormalities occurred in 6(1.7%) of the offspring. The perinatal mortality of the 'control' group of 146 women was 26.1%. Glucose intolerance persisted in at least 34.7% of gestational diabetic women postpartum. This study suggests that a specialized service for pregnant diabetic women from a Third World community can be implemented with good effect and limited expense. Late presentation of pregestational diabetic women is a problem. PMID- 8485966 TI - Continuing audit of diabetes service. PMID- 8485967 TI - The effect of a city-wide mass media campaign on the public awareness of diabetes. PMID- 8485968 TI - Caries experience of Native children of British Columbia, Canada, 1980-1988. AB - Surveys of the dental health of Native children in British Columbia, Canada, were conducted in 1980, 1984 and 1988 by Medical Services Branch, Health and Welfare Canada. Data were gathered on children turning 5, 7, 9, 11, 13, and 15 yr of age in each survey year. This paper analyzes the findings related to dental caries and the treatment of caries. Comparisons were made between the 1980 and 1988 surveys using Student's t-tests; data from the 1984 survey were included for comparison. Results of these surveys demonstrate a continuous improvement in the dental health of Native children between the years 1980 and 1988, but the improvement was limited to the permanent dentition. The deft for 5-yr-olds remained constant over the time interval. In contrast, the DMFT for each group significantly decreased from 1980 to 1988 (P < 0.05). The percentage of 5-yr-old children who were caries-free in the primary dentition remained constant, and primary tooth mortality (tooth abscessed or with crown destroyed) in 5-yr-olds did not change. However, the percentage of children surveyed with caries-free permanent teeth improved significantly at each survey year and permanent tooth mortality significantly declined (P < 0.05). The proportion of filled, compared with carious, primary and permanent teeth increased from 1980 to 1988. In contrast, the number of extracted primary teeth stayed relatively constant for 5 yr-olds, but the proportion of missing teeth declined significantly for all other age groups (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485969 TI - Effects of non-response on estimates derived from an oral health survey of older adults. AB - A major source of bias in health surveys is non-response on the part of those selected to take part in a study. In a survey of the oral health of older adults in Ontario, Canada, we used an initial telephone survey based on random digit dialing with a personal interview and clinical examination follow-up. The telephone survey was completed by 3033 individuals (78.0%) of those sampled. The follow-up was completed by only 907 (30.0%) of these subjects. Nevertheless, there were no major differences in the characteristics of those completing the telephone survey and those subsequently participating in the follow-up. Non response bias analysis indicated that differences between crude and adjusted estimates of the prevalence of oral conditions were small and the effect of non response on estimates of the relationship between socioeconomic status and oral health in this population were also small. These results indicate that response rates lower than those conventionally regarded as acceptable do not necessarily compromise the results of epidemiological studies. PMID- 8485970 TI - Norwegian adults' perceived need for coping skills to adjust to dental and non dental life events. AB - Limited attention has been paid to the importance which adults attach to dental, as opposed to other, life events. Consequently, the purpose of the present study was to determine how Norwegian adults rate the need for adjustment to cope with losing teeth or getting dentures, relative to some other life events, and to study effects of age, gender, level of education, place of residence, smoking, drinking and exercise habits. A representative, simple random sample of 400 residents of the County of Hordaland aged 20-69 yr received a mail questionnaire plus one reminder requesting demographic information and completion of a 48-item Social Readjustment Rating Questionnaire (SRRQ) in May 1990. The mean age of the 284 who responded (71%) was 41.1 yr (SD = 13.5 yr). The replies to the SRRQ were given on a graphic rating scale with end points "not difficult at all" (0 cm) and "more difficult than anything" (20 cm). Mean values were calculated and used to rank the life events. "Losing one or more teeth" was ranked 30 (mean = 11.8; SD = 5.6) and "getting dentures" 33 (mean = 13.8; SD = 5.5). "Losing one or more teeth" was on a par with life events like "trouble with other relatives" (mean = 11.7). "Getting dentures" occupied a position between "trouble with wife/husband" (mean = 14.3) and "wife/husband stopping work" (mean = 13.8). Multiple Classification Analysis revealed significant effects of education on "losing one or more teeth"; and of age, sex and education on "getting dentures" (P < 0.05). Furthermore, it was found that these two dental life events required an above average degree of readjustment according to the Social Readjustment Rating Questionnaire. PMID- 8485971 TI - Longitudinal statistical models for loss of sound surfaces. AB - Longitudinal data of 50-yr-old men, followed for 10 yr, were analyzed to identify variables which may be associated with healthy tooth surface loss. Three types of longitudinal models were used, arriving at similar conclusions. Predictors of sound tooth surface loss with aging included pocket depth, mobility, and recession. PMID- 8485972 TI - Burning mouth in a Finnish adult population. AB - Burning mouth syndrome is an oral pain disorder with a prevalence of 5-18% in patient materials. The aim of this study was to determine the prevalence of Burning mouth syndrome in a representative sample of the general adult population. Altogether 431 subjects (237 females, 194 males) participated in the study. Subjects were questioned about the experience of prolonged burning sensation; the site, severity, pattern, duration and possible associations of the onset of the burning sensation, and a thorough clinical examination was performed. In all, 15% of the subjects had experienced prolonged oral burning but a half of them had some clinically observable oral mucosal lesion or oral candidosis. The prevalence of the complaint was significantly higher in females than in males. PMID- 8485973 TI - Reproducibility of examiner performance for muscle and joint palpation in the temporomandibular system following training and calibration. AB - The purpose of this investigation was to assess examiner ability to consistently perform specific tasks related to muscle and joint palpation. Four trained and calibrated examiners were asked 1) to deliver index finger pressures within a high (1.5-2.1 kg) and low (0.5-1.1 kg) target pressure range and 2) to precisely locate one joint palpation and four muscle sites. After passing a calibration test, the performance of the examiners was monitored during the course of a replicability study assessing the consistency of clinical findings during repeated exams for TM disorders. (1) Index finger pressure was regularly tested over a 3-month period with a hand held pressure algometer, and the reading of each trial was recorded. Data analysis showed a high proportion of trials within the pressure range (overall 89.5%). Examiner performance across target range of pressures was statistically different for success rate and mean pressure delivered. The differences in the mean finger pressure delivered by each examiner (intraexaminer variation) was low and varied from 0.12 to 0.22 kg/cm2 for the desired range of pressures. (2) Paired examiners were asked to independently and sequentially mark palpation sites over the forehead, superficial and deep masseter, anterior temporalis, and lateral capsule of the temporomandibular joint. Replicability of site locations was assessed by measuring, with a boley gauge, the distance between sites selected by the paired examiners. Except for the superficial masseter and the anterior temporalis, the paired examiners selected palpation sites within a distance of 7 mm more than 85% of the time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8485974 TI - Effects of cannabis smoking on oral soft tissues. AB - The oral effects of cigarette smoking have been well documented but the effects of cannabis smoke on the oral environment have been poorly documented. Three hundred cannabis/tobacco/methaqualone smokers were examined. Two control groups consisting of 152 tobacco- and 189 non-smokers respectively were examined similarly. Health of the oral tissues and oral dryness was recorded. Lesions present included leukoedema, leukoplakia and numerous others. The only significant differences between lesions and conditions noted in cannabis users and controls occurred with respect to leukoedema, dry mouth and traumatic ulcer. PMID- 8485975 TI - AIDS and infection control: Dutch dental hygienists surveyed. AB - A sample of all dental hygienists practicing in the Netherlands besides Amsterdam (n = 669) and all dental hygienists practicing in Amsterdam (n = 118) were sent a questionnaire to assess the extent of compliance with the Dutch Health Council's guidelines to prevent HIV transmission in dental practices. The response rate was 64%, Gloves, masks and spectacles were widely used. Use of disposable parts of the three-way syringes, medical dishwasher, sterilizable handles and sterilizable three-way syringes was insufficient. Disinfection was too often preferred to sterilization. Compliance with the guidelines was not related to the size of the city of practice. Amsterdam hygienists did not comply better than hygienists not from Amsterdam. One third of the respondents asked questions to assess whether a patient was HIV seropositive. Evidently, the view of the Dutch Health Council that knowledge of seropositivity is not necessary, was not shared by a substantial part of the hygienists. Fear of infection appeared to be negatively related to experience in treating HIV-seropositive patients and, indirectly, to perceived knowledge about AIDS. PMID- 8485976 TI - Anxiety about dental hygienist treatment. AB - Although dental anxiety is a well investigated phenomenon in dental health care, remarkably little is known about anxiety reactions related to treatment carried out by the dental hygienist. In the present study anxiety reactions were measured among 101 patients attending the dental hygienist. General level of anxiety was assessed through the PAQ (Photo Anxiety Questionnaire; STOUTHARD, DE JONGH & HOOGSTRATEN, 1991), whereas an additional questionnaire was used to obtain information about specific stimuli and situations that might provoke anxiety in the dental hygienist situation. The results indicated that during dental hygienist treatment only 15% of the patients experienced no feelings of anxiety. Another 15% of the patients reported that a visit to the dental hygienist was more distressing than dental treatment. The level of anxiety appeared to be strongly related to a number of stimuli and situations, with actual pain (78%) and expected pain (67%) major anxiety provoking factors. The relation between pain and anxiety was highly significant, with highly anxious patients having more fear for pain than their low anxious counterparts. Also feelings and sounds of instruments, patient's helplessness and perceived lack of control over what happens were identified as important contributors to anxiety for the dental hygienist treatment. The results of this study suggests that treatment by the dental hygienist is a distressing event for many patients. PMID- 8485977 TI - Relationship between epidemiologic coronal caries assessments and practitioners' treatment recommendations in adults. AB - Caries incidence determinations in adults reflect dentists' treatment decisions as well as epidemiologists' caries assessments because many patients receive treatment between the two assessments that are required to determine incidence. Yet knowledge of the relationship between epidemiologically assessed caries and practitioners' treatment recommendations is poor. In this study, the proportions of practitioners recommending treatment for a tooth, and the reasons for those recommendations, were compared across teeth grouped by their caries status as determined from an epidemiologic assessment. On average, for a tooth deemed carious by epidemiologic assessment, a mean of almost 90% of examining practitioners recommended treatment. Most but not all of these recommendations for treatment of teeth with epidemiologically determined caries were for caries related reasons. Among teeth classified as sound by epidemiological assessment, the mean proportion of dentists recommending treatment was 11%. For restored, non carious teeth a mean of 35% of examining dentists recommended treatment. Across all noncarious teeth, 25% of all treatment recommendations were related to caries. The mean patient F increment (number of newly filled surfaces) that would result from treatment recommendations practitioners indicated as being associated with caries was slightly less than one-half of the total F increment. Thus, F increments may substantially overestimate caries incidence. PMID- 8485978 TI - Posttraumatic obsessive-compulsive disorder: a case study. AB - Recent epidemiologic evidence has pointed to a disproportionate rate of obsessive compulsive disorder (OCD) among high-combat-exposed Vietnam veterans. This case report describes an individual without previous overt psychopathology who under the stress of combat developed concurrent OCD and posttraumatic stress disorder (PTSD) persisting for more than 20 years. Phenomenologic, behavioral, psychodynamic, and biologic considerations all help to elucidate the potential role of emotional trauma in the pathogenesis of obsessions and compulsions. PMID- 8485979 TI - Should an axis for defense mechanisms be included in DSM-IV? AB - The purpose of this review is to address empirical evidence bearing on the desirability of including a Defense Mechanisms Axis in DSM-IV. The authors reviewed studies based on standardized clinical or self-report methods for assessing defense mechanisms. Information was sought pertinent to methods for assessment, relevance to clinicians with diverse theoretical perspectives, definitions, suitability for an axial format, complexity, reliability, clinical utility, and relationship to existing axes. Methods for reliably rating defense mechanisms have been developed, and data on the clinical utility of ratings have begun to accumulate. A consensus on definitions is emerging, and evidence supports a hierarchy of defenses based on their adaptiveness. Since training in psychodynamic theory and treatment approaches is required of residencies performed in the United States, all psychiatrists should be able to evaluate patient defenses. However, new methodologies have not been tested under usual clinical conditions with limited, "live" clinical data. A viable option for DSM IV is the inclusion of a defense mechanisms axis in an appendix of optional axes for use in special clinical and research settings. In addition to providing dynamically meaningful diagnostic data, this axis would facilitate expansion of the empirical data base on a standardized measure of defenses under conditions of routine clinical practice. PMID- 8485980 TI - Induced psychotic disorder: clinical aspects, theoretical considerations, and some guidelines for treatment. AB - We describe our experience with a case of folie a famille with role reversal, including the long-term course. In addition, the case reports published since 1974 were reviewed and an overview is given of the psychoanalytic and system theory concepts on the pathogenesis of induced psychotic disorder. The inductor often appears to be suffering from schizophrenia. No further indications could be found in the literature for a hereditary predisposition in the recipient. It is sometimes difficult to distinguish between the inductor and the recipient, owing to the circular character of induced psychotic disorder and the role reversal that sometimes occurs. The DSM-III-R criteria for induced psychotic disorder were found to be lacking in practice because of their disregard for the circular causality and the strict exclusion criteria. In the short term, physical separation of the inductor and recipient leads to better treatment results than nonseparation, particularly in the case of recipient children. Long-term results are seldom mentioned. On the basis of theoretical considerations, interventions that aim at separation in psychological terms are necessary to achieve favorable long-term treatment results. PMID- 8485981 TI - Otoneurological functioning in panic disorder patients with prominent dizziness. AB - Fifteen panic disorder patients with prominent dizziness underwent audiologic, caloric, and vestibuloocular reflex activity testing and were compared with normal controls. There were no abnormalities detected on audiologic and caloric tests. Compared with normal controls, panickers with dizziness showed a greater discrepancy between eye and head movements on vestibulo-ocular reflex activity in the dark. Panickers with prominent dizziness did not differ from a second control group of panickers with severe heart palpitations on a number of psychological tests. The results did not support the hypothesis that organic dizziness is etiologically important in the causation of panic or agoraphobia, but do suggest that vestibuloocular reflex activity should be further studied in panic disorder. PMID- 8485982 TI - Subjective cognitive dysfunction in schizophrenic and depressed patients. AB - We examined the experience of subjective cognitive dysfunction in schizophrenic and depressive patients and in patient control and normal control subjects, using questionnaires for measuring components of everyday attentional functioning and subjective cognitive difficulties. These subjective ratings were stable over a period of 3 months. Irrespective of diagnosis, psychiatric patients reported higher levels of distractibility, cognitive overload, and cognitive failures. The psychopathological correlates of these experiences and of reduced processing capacity and attentional control consisted primarily of symptoms of anxiety and depression and the corresponding personality traits. However, cognitive overload experiences were specifically associated with psychotic and psychotic-like symptoms. No correlation was found between negative symptoms and subjective cognitive efficacy. The discussion focuses on the energetic aspects of cognition and on problems of cognitive self-evaluation. It is argued that subjective cognitive measures are worth studying in their own right, and that they may be of interest to clinicians involved in rehabilitation programs. PMID- 8485983 TI - Morbid risks for major disorders and frequencies of personality disorders among spouses of psychiatric inpatients and controls. AB - Three hundred fifty-three psychiatric inpatients and their 192 living spouses and 98 control subjects and their 54 living spouses were examined and interviewed for affective, schizoaffective, schizophrenic (Research Diagnostic Criteria [RDC]), and personality disorders (DSM-III-R) using the Lifetime Version of the Schedule for Affective Disorders and Schizophrenia (SADS-L) and the Structured Clinical Interview for DSM-III-Personality Disorders (SCID). The morbid risks of spouses for unipolar depression were between .15 and .25, and those for other major disorders were below .03. The morbid risks of spouses of bipolar patients for unipolar depression exceeded those of other spouses by 50% without reaching statistical significance. Personality disorders were found in 44.6% of patients, in 8.4% of patients' spouses, and in 9.8% of healthy controls. There was only one couple in which the husband and wife had each had a major disorder before marriage. Only four husband-wife pairs suffered the same personality disorder. Spouses of patients do not have significantly more psychiatric disorders than healthy controls; therefore, assortative mating can only be of minor relevance in family studies. PMID- 8485984 TI - History and significance of childhood attention deficit disorder in treatment seeking cocaine abusers. AB - Thirty-five percent of 298 treatment-seeking cocaine abusers met DSM-III-R criteria for childhood attention deficit hyperactivity disorder (ADHD). Subjects with childhood ADHD were likely to be male (78%), meet Research Diagnostic Criteria (RDC) for conduct disorder (93%) and antisocial personality disorder (47%), and report a history of conduct disorder in first-degree relatives. With respect to those without the disorder and regardless of co-occurrence with sociopathy, cocaine abusers with childhood ADHD were younger at presentation for treatment and reported more severe substance use, earlier onset of cocaine abuse, more frequent and intense cocaine use, intranasal rather than freebase or intravenous use of cocaine, higher rates of alcoholism, and more previous treatment. This pattern of cocaine use is consistent with clinical descriptions of self-medication of residual symptoms of ADHD in cocaine abusers. Data from this study suggest that there may be more cocaine abusers with a history of ADHD than previously recognized in clinical samples of cocaine users, and that these individuals may differ in clinically meaningful ways from those without childhood ADHD. Moreover, the poorer outcome of subjects with ADHD in this sample underlines the importance of identifying and treating residual symptoms of ADHD in cocaine abusers. PMID- 8485985 TI - Primary depressives with secondary alcoholism compared with alcoholics and depressives. AB - While a subset of depressed patients are believed to "self-medicate" their depression with alcohol, there are no studies comparing the phenomenological and diagnostic characteristics of patients with primary depression and secondary alcoholism with those of patients with depression or alcoholism alone. In this study, we compared 11 patients from each of these three diagnostic groups in terms of past history and current clinical presentation. The patients were matched for age, sex, and level of function. Comorbid patients were most likely to meet criteria for sedative dependence and panic disorder, and had higher scores on the Hamilton Anxiety Scale. In addition, they scored higher on a hypomania scale and had more first-degree relatives with a history of drug abuse. PMID- 8485986 TI - Gender differences in psychiatric morbidity among alcohol misusers. AB - Sociodemographic characteristics, patterns and effects of alcohol abuse, and psychiatric morbidity were compared in 121 men and 121 women using structured interviews, and diagnostic criteria according to the DSM-III and Hamilton Depression Rating Scale were applied. Women were more likely to be binge drinkers, to have premorbid anxiety, and to be diagnosed with primary depression. Men cited social reasons for drinking, whereas women were more likely to drink to alleviate anxiety. Women also were more likely to have a family history of psychiatric disorder and/or alcohol misuse. More women were drinking at home alone than men, but almost as many were drinking openly with their spouses or friends. PMID- 8485987 TI - Biochemical basis of DNA replication fidelity. AB - DNA polymerase is the critical enzyme maintaining genetic integrity during DNA replication. Individual steps in the replication process that contribute to DNA synthesis fidelity include nucleotide insertion, exonucleolytic proofreading, and binding to and elongation of matched and mismatched primer termini. Each process has been investigated using polyacrylamide gel electrophoresis (PAGE) to resolve 32P-labeled primer molecules extended by polymerase. We describe how integrated gel band intensities can be used to obtain site-specific velocities for addition of correct and incorrect nucleotides, extending mismatched compared to correctly matched primer termini and measuring polymerase dissociation rates and equilibrium DNA binding constants. The analysis is based on steady-state "single completed hit conditions", where polymerases encounter many DNA molecules but where each DNA encounters an enzyme at most once. Specific topics addressed include nucleotide misinsertion, mismatch extension, exonucleolytic proofreading, single nucleotide discrimination using PCR, promiscuous mismatch extension by HIV 1 and AMV reverse transcriptases, sequence context effects on fidelity and polymerase dissociation, structural and kinetic properties of mispairs relating to fidelity, error avoidance mechanisms, kinetics of copying template lesions, the "A-rule" for insertion at abasic template lesions, an interesting exception to the "A-rule", thermodynamic and kinetic determinants of base pair discrimination by polymerases. PMID- 8485988 TI - Chromosomal assignments of genes for rat glutathione S-transferase Yb1 (GSTA3) and Yb2 (GSTA4) subunits. AB - Chromosomal assignments of genes for rat glutathione S-transferase Yb1 (GSTA3) and Yb2 (GSTA4) subunits were performed by Southern blot analyses of somatic cell hybrid DNAs. Both GSTA3 and GSTA4 were assigned to rat chromosome 2. PMID- 8485989 TI - A method for testing the nonrandomness of chromosomal breakpoints. AB - Testing the nonrandomness of breakage at a chromosome band is an essential step fo identifying a fragile site. In this paper, we propose a method derived by using the relationship between the binomial and F distributions for testing nonrandomness. The method is simple in calculation. It was applied to the detection of fragile sites for Chinese patients with colorectal carcinoma. PMID- 8485990 TI - The effect of 13;14 Robertsonian translocations on germ-cell differentiation in infertile males. AB - Two infertile men heterozygous for a 13;14 Robertsonian (Rb) translocation were investigated by means of synaptonemal complex studies, testicular histology, and semen analysis. In both individuals interaction between the Rb trivalent and the XY pair was observed. Twenty percent of pachytene cells analyzed in one patient showed XY-trivalent association which correlated with malformed spermatids; the higher rate of XY-trivalent association (approximately 47%) in the second proband corresponded with complete spermatogenic arrest. The data presented indicate a positive correlation between increased frequency of XY trivalent association and the degree of germ-cell impairment. PMID- 8485991 TI - Interstitial localization of telomeric DNA sequences in the Indian muntjac chromosomes: further evidence for tandem chromosome fusions in the karyotypic evolution of the Asian muntjacs. AB - The Indian muntjac is believed to have the lowest chromosome number in mammals (2n = 6 in females and 2n = 7 in males). It has been suggested that a series of tandem chromosome fusions from an ancestral Chinese muntjac-like species (2n = 46) may have occurred during the karyotypic evolution of the Indian muntjac. In an earlier study, hybridization signals generated by the Chinese muntjac centromeric heterochromatin DNA probe (C5) were found to be distributed interstitially in the chromosomes of the Indian muntjac, providing supportive evidence for the tandem chromosome fusion theory. In this study, the highly conserved human telomeric DNA sequence (TTAGGG)n was localized by fluorescence in situ hybridization (FISH) on the metaphase chromosomes of three Cervidae species: the Indian muntjac, Chinese muntjac, and woodland caribou. As expected, hybridization signals were observed at the termini of almost every chromosome in all three species. In addition, interstitial hybridization signals were detected in chromosomes 1 and 2 of the Indian muntjac. The observed interstitial telomeric signals appeared to correspond to specific interstitial centromeric heterochromatin sites. These interstitial telomeric signals could represent remnant DNA sequences from the ancestral species telomeres, further supporting the tandem chromosome fusion theory. Furthermore, these observations permit the elucidation of the chromosome sites where breakage and fusion most likely occurred during the restructuring of the ancestral Chinese muntjac-like chromosomes to form the present day Indian muntjac karyotype. PMID- 8485992 TI - Co-dominance of radioresistant DNA synthesis in a group of AT-like Chinese hamster cell mutants. AB - The relation of radiosensitivity and radioresistant DNA synthesis (RDS) was studied in the AT-like Chinese hamster cell mutants V-C4, V-E5, and V-G8 of the same complementation group. Proliferating hybrid cell lines obtained after fusion of the AT-like hamster cell mutants with their parental V79 cells showed only very partial complementation of RDS, while radiosensitivity with respect to cell killing was fully complemented in these hybrid cells. Therefore, RDS behaves as a (co-)dominant feature in hybrids of AT-like mutants and wild-type V79 cells, indicating that RDS cannot be used for complementation analysis of X-ray sensitive Chinese hamster cells. In contrast to the intraspecies hybrids, a full complementation of RDS was observed in interspecies hybrids between the rodent AT like mutants and human (HeLa) cells, suggesting a species-specific regulation of DNA synthesis. These results indicate that radiosensitivity and RDS are pleiotropic effects of the same afflicted gene. PMID- 8485993 TI - A high-resolution banding pattern idiogram of Monodelphis domestica chromosomes (Marsupialia, Mammalia). PMID- 8485994 TI - Detailed characterization of a human 8q24.1 microdissection library and generation of "sequence-tagged sites". AB - A total of 533 clones from a human 8q24.1 microdissection library was analyzed by automatic DNA sequencing. Three hundred and thirty-seven different insert sequences were found. The insert size ranged from 45 to 376 bp (mean, 170 bp). Eighty-six percent (291/337) of these sequences were free of repetitive DNA. Each of 19 clones tested was successfully translated into a sequence-tagged site. We conclude that the microdissection library is a rich source of DNA markers for 8q24.1. PMID- 8485995 TI - Cytogenetics of bisexual/unisexual species of Poecilia. V. Unisexual poeciliids with anomalous karyotypes from northeastern Mexico. AB - Unisexual poeciliid fishes collected from two localities in the Soto la Marina drainage have been analyzed. Unisexual diploid and triploid specimens with anomalous karyotypes were found among karyotypically normal specimens. Chromosomal data are discussed in light of the origin of clonal diversity in unisexual/bisexual breeding complexes and with regard to the role of triploids in these breeding complexes. PMID- 8485996 TI - Mapping of the human cardiac Na+/Ca2+ exchanger gene (NCX1) by fluorescent in situ hybridization to chromosome region 2p22-->p23. AB - The cDNA that encodes the human Na+/Ca2+ exchanger (NCX1) involved in regulation of intracellular calcium levels has been isolated from a cardiac cDNA library. Using fluorescent in situ hybridization, the human cDNA was mapped to chromosome region 2p23-->p22 by co-hybridization with fluorescinated alu517-PCR amplified total human DNA to obtain an R-banding pattern. PMID- 8485997 TI - Chromosomal evidence for a hybrid origin of diploid parthenogenetic females from the unisexual-bisexual Lepidodactylus lugubris complex (Reptilia, Gekkonidae). AB - Chromosome banding analysis of seven diploid parthenogenetic females from Polynesian and Southeast Asian populations of the unisexual-bisexual Lepidodactylus lugubris complex (Reptilia, Gekkonidae) showed that the unisexual karyotype consists of two different haploid sets. Similar analysis of an L. lugubris male from a bisexually reproducing population revealed two identical chromosome complements, the banding pattern generally matching that of the females, although many chromosomes were obviously different. These observations suggest that the gonochoristic males belong to a taxon related to the parthenogenetic female taxon but are not a direct ancestor of the latter. The data also offer strong evidence for a hybrid origin of diploid parthenogenetic females in L. lugubris and suggest that a high degree of chromosomal heterogeneity may be the leading reason for the evolutionary selection of a modified meiotic process in this species, allowing production of unreduced oocytes and, consequently, of a unisexual mode of reproduction. PMID- 8485998 TI - Is the MDI doomed to extinction? PMID- 8485999 TI - Ultrahigh frequency ventilation. Nouvelle ventilation or just old hash? PMID- 8486000 TI - Long-term ventilatory support in the community. PMID- 8486001 TI - Self-efficacy. PMID- 8486003 TI - Yes, there is life after ventilation. PMID- 8486002 TI - CEASE (Collaborative European Anti-Smoking Evaluation). A challenging multicenter trial organized by the European Respiratory Society. PMID- 8486004 TI - Natural history of left ventricular function in patients with uncomplicated acute myocardial infarction. AB - To investigate the serial changes of the infarcted and the noninfarcted areas, first-pass radionuclide angiocardiography was performed in 16 patients with uncomplicated anterior myocardial infarction (MI) at four weeks, one year, and two years after the onset of MI. Global ejection fraction (EF) and regional EF of the infarcted area improved significantly from four weeks to one year after MI (from 39 +/- 16 to 44 +/- 16 percent, 23 +/- 3 to 29 +/- 5 percent, both p < 0.01), but did not change from one year to two years after MI. Regional EF of the noninfarcted area and left ventricular end-diastolic and end-systolic volume did not change during the study period. There was a significant relation in the direction of the changes of global EF and regional EF of the infarcted area during the first year after MI, whereas no relation was observed between the changes of global EF and regional EF of the noninfarcted area. A greater improvement in regional EF of the infarcted area was observed in seven patients who had spontaneous recanalization compared with nine patients with totally occluded coronary arteries. Thus, a significant improvement in cardiac function, mainly due to the increase in regional EF of the infarcted area, was observed during the first year after MI, which was related to patency of coronary artery. PMID- 8486005 TI - Pulmonary function and respiratory chemosensitivity in moderately obese patients with sleep apnea. AB - To determine whether moderately obese, normocapnic, sleep apnea patients are distinguished from normal obese individuals by differences in waking pulmonary function and respiratory chemosensitivity, we compared the waking pulmonary function, hypercapnic, and hypoxic ventilatory responses of 35 nonhypercapnic sleep apnea patients (32 men and 3 women) with those of 17 age-, sex-, weight-, and obesity-matched nonapneic control subjects (16 men and 1 woman). The waking ventilatory response to hypercapnia was lower among sleep apnea patients (mean +/ SD, 2.05 +/- 1.29 L/min/mm Hg) than control subjects (3.02 +/- 2.05 L/min/mm Hg, p < 0.05). Patients with sleep apnea demonstrated a higher waking PaCO2 (40.4 +/- 2.9 vs 37.0 +/- 2.7 mm Hg, p < 0.001), and a lower waking PaO2 (81.4 +/- 11.7 vs 89.7 +/- 10.4 mm Hg, p < 0.03). The waking hypoxic ventilatory response, however, was not significantly different between the groups. Moreover, control subjects had a higher total lung capacity than sleep apnea patients (6.99 +/- 1.12 L and 6.27 +/- 1.09 L, respectively, p < 0.05). The lower hypercapnic ventilatory response, higher waking PaCO2, and lower total lung capacity in the sleep apnea patients resemble the pattern observed in patients with pickwickian syndrome. This suggests that disturbances in pulmonary function and ventilatory control in moderately obese sleep apnea patients are intermediate along a continuum from normal obesity to the pickwickian syndrome. PMID- 8486006 TI - Sleep apnea syndrome and end-stage renal disease. Cure after renal transplantation. AB - We report two patients undergoing maintenance hemodialysis who presented with sleep apnea syndrome (SAS). The first patient is a 36-year-old man with a terminal Berger's glomerulopathy and associated obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index [AHI] = 80). He was receiving home hemodialysis and was treated by nasal continuous positive airway pressure (CPAP). After successful renal transplantation, his symptoms completely disappeared, and control polysomnography greatly improved (AHI = 9). The second patient had hypokalemic nephropathy with severe, uncontrolled hypertension and hypertensive myocardiopathy. He was receiving home dialysis and showed a central sleep apnea syndrome with an AHI of 51. He also was successfully treated by nasal CPAP. After renal transplantation, his sleep improved, insomnia disappeared, and polysomnography showed great improvement (AHI = 5). We discuss the role of periodic breathing related to end-stage renal disease associated metabolic abnormalities, as a pathogenetic factor of these SASs. Respiratory correction of chronic metabolic acidosis, "uremic toxins," "middle molecules," and hemodialysis are all evoked as etiologic factors and their own roles are discussed. PMID- 8486007 TI - Adiposity and cardiovascular risk factors in men with obstructive sleep apnea. AB - STUDY OBJECTIVE: To assess anthropometric characteristics of patients with obstructive sleep apnea (OSA) and their relationship to cardiovascular risk factors (dyslipidemia, hypertension, glucose intolerance) and severity of breathing abnormalities during sleep. DESIGN: Case series. SETTING: Referral based sleep disorder center serving Rhode Island and Southeastern Massachusetts. PATIENTS: Forty-five men, 26 to 65 years old, with OSA diagnosed by clinical and polysomnographic criteria. RESULTS: By national health survey criteria, 51 percent of patients were in the upper fifth percentile for weight, whereas 91 to 98 percent were in the upper fifth percentile for skinfold thicknesses (triceps, subscapular, triceps plus subscapular). Severe upper body obesity, as defined by a waist-hip ratio (WHR) greater than or equal to 1.00, was present in 51 percent of the patients. The WHR, however, did not correlate significantly with the severity of respiratory disturbances during sleep. The patients had higher prevalences of hypertension and impaired glucose tolerance than expected, but normal prevalences of hypercholesterolemia, low high-density lipoprotein cholesterol, and overt diabetes mellitus. Skinfold thicknesses correlated more closely with the severity of OSA than did body mass index (BMI) or neck circumference. CONCLUSION: Men with OSA have a marked excess of body fat that is not always reflected in measurements of body weight or BMI. Also, upper body obesity, hypertension, and impaired glucose tolerance occur more frequently than expected in this population. Severe adiposity may not only promote development of the respiratory abnormalities of OSA, but also may contribute directly to the increased cardiovascular risk associated with OSA. PMID- 8486008 TI - 24-hour ambulatory blood pressure variability in obstructive sleep apnea syndrome. AB - The 24-h ambulatory blood pressure (24h-ABP) was examined in 21 men, aged 38 to 65 years (mean 50.6), with obstructive sleep apnea syndrome (OSAS) and in 123 normal male control subjects, aged 40 to 60 years (mean 48.1) who did not have OSAS, obesity, autonomic nervous system abnormality, cardiac disease, or respiratory disease (group C), to assess the role of apneas in the circadian variation of blood pressure (BP). The 24h-ABP patterns in OSAS patients were classified into three types as follow: normotensive OSAS patients with normal BP throughout the 24-h period with nocturnal BP fall (type 1); hypertensive OSAS patients with progressive BP elevation from onset of sleep to early morning (type 2); and hypertensive OSAS patients with elevated BP (systolic BP > or = 140 mm Hg or diastolic BP > or = 90 mm Hg) at any time during a 24-h period (type 3). It was concluded that the circadian BP variation in type 1 was almost identical to the level and pattern of group C; the circadian variations in types 2 and 3 were significantly different from that of group C; and the patients with types 2 and 3 BP patterns had more severe OSAS than type 1 patients. The severity of OSAS was an important factor in nocturnal elevation of BP, hence affecting the circadian variation of BP. Noninvasive 24h-ABP monitoring is a useful procedure for understanding the clinical features of OSAS patients with or without hypertension. PMID- 8486009 TI - Validation of new pulsed Doppler echocardiographic techniques for assessment of pulmonary hemodynamics. AB - In preparation for a vasodilator study on chronic obstructive pulmonary disease (COPD), we investigated the reliability of recently described pulsed Doppler techniques for estimating pulmonary artery pressure (PAP) and cardiac output (CO). Our aims were to determine the following: (1) the imaging success rate for pulsed Doppler measurements; (2) the repeatability of the measurements, and interobserver and intraobserver variability; and (3) the accuracy of Doppler compared with catheter measurements. Doppler studies were attempted in 81 patients (cardiac disease [23], COPD [22], sleep apnea [32], and normal subjects [4]). Suitable images were obtained in 68 subjects (84 percent) and in 76 subjects (94 percent) for PAP and CO estimations, respectively. The lowest imaging success rates were in COPD patients (68 percent for PAP and 86 percent for CO estimation). Repeatability of the techniques was assessed in four cardiac patients and three healthy volunteers by performing four replicate studies in each subject over 1 h. Intrasubject coefficient of variation was < 10 percent for PAP and < 5 percent for CO. The intraobserver variability for Doppler estimation of systolic and mean PAP was 5.5 percent and 5.8 percent, respectively. The corresponding values for interobserver variability were 6.7 percent and 6.2 percent. Intraobserver and interobserver variability for "nongeometric" method of estimating CO was 5.1 percent and 5.9 percent, respectively. Agreement was good between catheter-measured and Doppler-estimated PAP in the 27 patients tested (cardiac [19] and COPD [8]) for both mean and systolic pressures (r = 0.96 and r = 0.97, respectively). The correlations between thermodilution and Doppler estimations of CO in eight COPD patients were 0.77 ("geometric" technique) and 0.97 ("nongeometric" technique). We conclude that pulsed Doppler techniques can be used to obtain accurate and reproducible quantitative information on pulmonary hemodynamics in a wide range of patients. Suitable Doppler images can be obtained in more than two thirds of COPD patients. PMID- 8486010 TI - Felodipine improves pulmonary hemodynamics in chronic obstructive pulmonary disease. AB - Pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis. Reduction of pulmonary artery pressure in COPD by prolonged oxygen treatment has been shown to be associated with increased survival. In an attempt to find a suitable pharmacologic method of reducing pulmonary artery pressure and pulmonary vascular resistance in COPD, we enrolled 13 stable pulmonary-hypertensive, hypoxemic COPD patients in a study to test the effects of felodipine, a relatively new, vascular-selective calcium antagonist. Doppler echocardiography was used to estimate pulmonary artery pressure and cardiac output before treatment, 2, 7, and 12 weeks during felodipine treatment (10 to 20 mg/d), and after a 1-week placebo washout period. Measurements of lung function, arterial blood gases, and exercise capacity during an incremental bicycle ergometer test were also performed at intervals during the study period. Three patients withdrew from the study and of the remaining 10, 8 had some side effects of medication (peripheral edema or headache) that improved either spontaneously or following a reduction in drug dose. In the 10 patients who completed the study (8 male; mean age, 67 years), felodipine resulted in significant reductions in mean pulmonary artery pressure (22 percent) and total pulmonary (vascular) resistance (30 percent) and increases in cardiac output (15 percent) and stroke volume (13 percent) compared with baseline measurements and those taken after placebo washout. These effects were sustained over the 12 weeks of felodipine treatment. There was no adverse effect of felodipine treatment on pulmonary gas exchange at rest or during exercise and no change in lung function or exercise capacity. We conclude that in pulmonary hypertensive, hypoxemic COPD patients, felodipine substantially improves pulmonary hemodynamics. PMID- 8486011 TI - Nutritional status of patients with chronic obstructive pulmonary disease and acute respiratory failure. AB - The prevalence and features of malnutrition in COPD patients have been studied extensively in stable conditions but are poorly defined in the presence of acute respiratory failure (ARF). Nutritional status was prospectively assessed, on hospital admission, in 50 consecutive COPD patients presenting with ARF, 27 of them requiring mechanical ventilation (MV). Malnutrition, defined on a multiparameter nutritional index, was observed in 60 percent (30/50) of all patients, and in 39 percent (13/33) of those whose body weight was equal to or above 90 percent ideal body weight (IBW). Malnutrition was more frequent in those patients who required MV than in those who did not (74 percent vs 43 percent, p < 0.05). Subcutaneous fat stores were decreased (triceps skinfold thickness [TSF] < 80 percent pred) in 68 percent of patients, and markedly depleted (TSF < 60 percent pred) in 52 percent of them. The indices of lean body mass, ie, mid-arm muscle circumference (MAMC) and creatinine height index (CHI) were decreased in, respectively, 42 percent and 71 percent of patients, but MAMC was severely depressed (< 60 percent pred) in only 6 percent of them. A severe decrease of prealbumin (< 100 mg/L), retinol-binding-protein (< 20 mg/L), and albumin (< 20 g/L) serum concentrations was observed in, respectively, 22 percent, 28 percent, and 4 percent of patients. These results suggest that an assessment of nutritional status using a multiparameter approach should be systematically performed in COPD patients with ARF, especially in those requiring MV, as malnutrition may have deleterious effects on weaning off MV. PMID- 8486012 TI - The influence of spring and summer New England meteorologic conditions on the respiratory status of patients with chronic lung disease. AB - To determine whether meteorologic conditions affect the respiratory status of individuals with chronic lung disease, we asked 14 patients who had completed outpatient pulmonary rehabilitation to record the following information daily during the spring and summer of 1991: (1) dyspnea on arising (morning dyspnea); (2) dyspnea throughout the day (daytime dyspnea); (3) peak expiratory flow rate (PEFR); (4) mood; and (5) the presence of lower respiratory tract infection (LRI). The effect of local meteorologic conditions and LRI frequency on morning and daytime dyspnea, PEFR, and mood were analyzed for spring and summer seasons using a linear regression technique that controlled for first-order autocorrelation. The LRI frequency and the preceding day's respiratory status were the most significant predictors of either season's daily variation in respiratory status. During spring, the only meteorologic condition associated with respiratory status was precipitation: rainfall was directly related to increased morning and daytime dyspnea. Meteorologic conditions were not related to changes in PEFR or mood. During summer, the combination of higher temperature, rise in barometric pressure, and increased LRI frequency best predicted increased morning dyspnea, while the combination of higher temperature and rise in barometric pressure best predicted reduced PEFR. Meteorologic conditions were not related to changes in daytime dyspnea or mood. Precipitation in spring and a combination of high temperature and rise in barometric pressure in summer best predicted deterioration in the respiratory status of this group of patients with chronic lung disease. PMID- 8486013 TI - Changes in transcutaneous oxygen partial pressure as an index of response to inhaled methacholine in asthmatic patients. AB - Bronchoconstriction and hypoxemia have been reported to occur during airway challenges, but the correlation between changes in forced expiratory volume in 1 s (FEV1) and transcutaneous oxygen partial pressure (tcPO2) during methacholine provocation tests has not yet been established (to our knowledge). In 15 symptom free atopic asthmatic patients and 5 normal subjects, variations in tcPO2 and FEV1 were simultaneously measured during inhalation of doubling methacholine concentrations; the drug concentrations causing a 20 percent decrease in control FEV1 and tcPO2 (PC20FEV1 and PC20tcPO2, respectively) were subsequently calculated. In patients, geometric mean PC20FEV1 and PC20TcPO2 were 1.31 (range, 0.16 to 5.19) and 1.26 (range, 0.29 to 5.82) mg/ml, respectively. In addition, in six patients, methacholine-induced fall in tcPO2 was accompanied by similar changes in arterial PO2. Methacholine inhalation caused no change in tcPO2 or FEV1 in normal subjects. The independent effects of deep breath tests and bronchoconstriction on PC20tcPO2 were studied in five patients challenged on two separate occasions, with and without FEV1 assessment; in these patients, PC20tcPO2 were similar on both the study days. The results indicate that, in asthmatic patients, methacholine-induced bronchoconstriction causes parallel decreases in FEV1 and tcPO2. The tcPO2 monitoring may serve as a tool in the assessment of airway hyperreactivity when active patient's cooperation is scarce. PMID- 8486014 TI - Acute effects of nifedipine on systolic and diastolic ventricular function in patients with chronic obstructive pulmonary disease. AB - To evaluate how nifedipine influences systolic and diastolic ventricular function, the effects of 20 mg sublingual nifedipine were studied in 13 stable COPD patients. Nifedipine induced no change in mean pulmonary arterial pressure, decreased mean arterial pressure, pulmonary and systemic vascular resistance index, and increased heart rate and cardiac index. It also caused an increase in right and left ventricular ejection fractions. The end-diastolic volume index of both ventricles remained unchanged, whereas the end-systolic volume index tended to decrease without reaching a significant level, and the right ventricular contractility increased. After nifedipine administration, right and left ventricular compliance increased. This study suggests that short-term administration of nifedipine improves the systolic function by a decrease in ventricular afterload and an increase in ventricular contractility and increases the ventricular compliance by a reflex sympathetic stimulation and an afterload reduction. PMID- 8486015 TI - Changing patterns of aerosol deposition during methacholine bronchoprovocation. AB - During bronchoprovocation testing with methacholine, induced changes in airway geometry are known to affect sites of drug deposition. However, it is not known if changes in these sites determine measured responsiveness. We assessed the importance of sites of deposition as determinants of reactivity by comparing particle behavior in two subject groups with and without hyperresponsiveness. By administering radiolabeled aerosols of similar aerodynamic characteristics to methacholine aerosol, we measured the deposition pattern in terms of the specific central to peripheral ratio (sC/P) before and after methacholine inhalation (sC/P1 and sC/P2, respectively) and thereby quantified the changes in deposition sites that occur during the course of a typical bronchoprovocation test. Subjects whose FEV1 decreased by 20 percent or greater were classified as methacholine responsive (MR; nine subjects), and the remainder were classified as non methacholine responsive (NMR; seven subjects). The two groups had similar baseline FEV1 percent predicted (FEV1 percent) and initial deposition patterns (sC/P1) with particles depositing primarily in peripheral airways (mean +/- SE; sC/P1 1.43 +/- 0.070 and 1.39 +/- 0.65, MR and NMR, respectively, p = NS). Following methacholine inhalation, the deposition pattern changes markedly for all subjects with particles depositing primarily in central airways (sC/P2 2.58 +/- 0.24, p = 0.001, and 2.15 +/- 0.22, p = 0.001 from baseline, p = NS between groups) By definition, the MR subjects had a significantly greater change in FEV1 than the NMR subjects. Preferential deposition in central airways occurs in all subjects during bronchoprovocation testing and does not significantly determine methacholine responsiveness. PMID- 8486016 TI - Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease. AB - Asthmatic subjects with tidal expiratory flow limitation have mucociliary clearance (MC) impairment in central airways. Because tidal flow limitation develops in COPD, it is possible that regional MC in these patients also may be affected. We tested this hypothesis by measuring MC in the presence or absence of flow limitations. Patients with COPD and chronic flow limitation were compared with non-flow-limited normal volunteers. Deposition was normalized for regional lung volume and expressed as the specific central to peripheral (sC/P) ratio. In COPD subjects, clearance from the whole lung and central airways was significantly different from that of normal subjects after 20 min of observation. In the peripheral airways, there were no significant differences between COPD and normal subjects. An alternative analysis of regional MC indicated patients retained particles in central airways while normal subjects, with intact MC, emptied central airways. Thus, COPD subjects with tidal expiratory flow limitation have impaired MC in their central airways. PMID- 8486017 TI - Supported arm exercise vs unsupported arm exercise in the rehabilitation of patients with severe chronic airflow obstruction. AB - OBJECTIVE: Compare unsupported (UAEx) vs supported (SAEx) arm exercise in training of patients with severe chronic airflow obstruction (CAO). DESIGN: Randomized trial of UAEx vs SAEx training added to a 10-week outpatient program of lower extremity (LE) exercise training, respiratory muscle training, breathing retraining, psychological support, and teaching. SETTING: The Lahey Clinic Medical Center, a tertiary referral center. PATIENTS: Forty patients with CAO entered the rehabilitation program with 32 completing training and testing. INTERVENTIONS: All underwent progressive bicycle ergometer and treadmill training and respiratory muscle training using a threshold inspiratory pressure trainer. Patients were randomized to progressive SAEx training (arm cycle ergometer, n = 17) or UAEx training (raising weighted dowel, n = 18). MAIN OUTCOME MEASURES AND RESULTS: There was no significant difference in disease severity or exercise capacity between the two groups. Twelve-min walk test, bicycle ergometer power output, and respiratory muscle function improved with no significant difference in improvement between the two groups. Both groups showed similar improvements in arm ergometer testing while those trained with UAEx showed greater improvement in dowel testing (UAEx > SAEx, p = 0.002). In 17 patients VO2isotime (time at which patient performed pre-training and post-training tests) was measured during dowel testing. Only those trained with UAEx showed decreases in VO2isotime (UAEx trained, p = 0.02; SAEx, p = 0.18). VO2 during the last minute of a 2-min period of simple arm elevation was also measured in 17 patients. Only those trained with UAEx showed decreases in VO2 (UAEx, p = 0.02; SAEx, p = 0.20). CONCLUSION: We confirm that a pulmonary rehabilitation program incorporating exercise training improves LE and respiratory muscle function. Arm exercise training improved arm activity with greater increases in unsupported arm activity seen in those trained with unsupported arm training. Metabolic cost of UAEx decreased only in those trained with UAEx. As UAEx is typical of activities of daily living in patients with CAO, the changes seen with UAEx training may be of greater clinical significance. Arm training should be incorporated in exercise training and a simple program of UAEx appears the optimal format. PMID- 8486018 TI - Ultrasonically guided aspiration biopsy in osteolytic bone lesions of the chest wall. AB - Sixteen consecutive patients with one or more osteolytic bone lesions of the chest wall radiologically confirmed underwent ultrasonically guided aspiration biopsy. Nine patients (56.2 percent) had bronchogenic carcinoma with a direct extension. Other diagnostic techniques had failed to diagnose disease in these patients. The lesion showed heterogeneous echogenicity (n = 16) caused by the hyperechoic signals of bone fragments. The interruption of the cortex bone was detected in all cases and extraosseous tumor portion in 14 of 16 patients (87.5 percent). No respiratory motions of the lesion could be demonstrated (n = 16). Definitive histologic diagnosis was made in 14 of the 16 patients (87.5 percent). In malignancy, diagnosis was established in 13 of 14 patients (92.8 percent). Of two confirmed benign lesions, one diagnosis of tuberculosis was obtained. No complication occurred. Sonography and consequently ultrasonically guided aspiration biopsy are a useful, accurate, safe, and low-cost technique for osteolytic lesions in thoracic diseases. PMID- 8486019 TI - A comparison of manual to mechanical chest percussion for clearance of alveolar material in patients with pulmonary alveolar proteinosis (phospholipidosis). AB - To our knowledge, there are no studies that compare the effectiveness of manual chest percussion (MN), mechanical chest percussion (MC), and no percussion (NP) for removing the proteinaceous material found in the alveoli of patients with pulmonary alveolar proteinosis (PAP) while undergoing whole-lung bronchopulmonary lavage (BPL). We analyzed the optical densities (OD) of 27 bottles of effluent from three BPLs of a patient with PAP. One technique was used per bottle. The order of techniques was balanced within each nine-bottle series and among the three BPLs. The mean OD for MN (0.933 +/- 0.494) was significantly superior to MC (0.477 +/- 0.265) (p < 0.0005) and NP (0.318 +/- 0.242) (p < 0.0001). We conclude that MN is superior to MC and NP and increases the therapeutic results of BPL for PAP. PMID- 8486020 TI - Use of ultrahigh frequency ventilation in patients with ARDS. A preliminary report. AB - STUDY OBJECTIVE: Our objective was to compare the efficacy of ultrahigh frequency ventilation (UHFV) (frequencies > 3 Hz) with respect to oxygenation, airway pressures, and hemodynamic parameters in patients with adult respiratory distress syndrome (ARDS) who were not responding to conventional ventilation. DESIGN: We used a prospective, multicenter, nonrandomized study design in which each patient served as his own control. SETTING: Three university-affiliated, tertiary-care medical centers participated. PATIENTS: Persons aged 16 to 79 years old with ARDS and unresponsive to conventional ventilation, as defined by a Food and Drug Administration (FDA) approved protocol, were included. INTERVENTIONS: Ninety patients who were not responding to conventional ventilation were changed to UHFV using a microcomputer-controlled device. MEASUREMENTS AND RESULTS: The patient's blood gas, hemodynamic, and airway pressure variables were measured just before, and at 1 and 24 h after the switch to UHFV. We demonstrated clinically significant improvements in arterial oxygen tension (PaO2) and reductions in peak and mean inspiratory pressures. CONCLUSIONS: In a multicenter study, UHFV improved respiratory gas exchange and reduced airway pressure variables at both 1 h and 24 h after the onset of UHFV when compared with conventional ventilation just prior to the change and without hemodynamic deterioration, in patients with severe ARDS. PMID- 8486021 TI - Topical treatment of pulmonary aspergilloma by antifungals. Relationship between duration of the disease and efficacy of therapy. AB - Twelve patients with aspergilloma were treated with intracavitary or endobronchial administration of antifungals. Patients with successful therapy had significantly shorter mean duration of the disease course (3.6 months) than the less effective group (44.4 months, p < 0.01). Minimal inhibitory concentrations of antifungal agents against isolated strains of aspergilli were considerably lower than estimated intracavitary concentrations of the antifungals. A pathologic examination suggested that the old mycetoma was for the most part comprised of dead mycelial cells, against which antifungal agents were not effective. However, clinical improvement was obtained, regardless of the roentgenographic improvement. Our study suggested that early diagnosis and therapy are recommended to achieve better therapeutic effect. PMID- 8486022 TI - Squamous metaplasia of the bronchial mucosa and its relationship to smoking. AB - We performed flexible fiberoptic bronchoscopy (FFB) on 106 heavy cigarette smokers. Six bronchial biopsy specimens, obtained from the carina and five major bronchi, were screened for squamous metaplasia. Individual biopsy specimens were sectioned into 4-microns sections, and a metaplasia index (MI), or percentage of sections containing squamous metaplasia, was determined. Metaplasia was noted at one or more biopsy sites in 66 of 99 subjects (seven were excluded from the analysis). Twenty-five percent of the subjects showed metaplasia at three or more biopsy sites, and one subject had metaplasia on all six biopsy specimens. The presence of squamous metaplasia varied from 40.4 percent in the right lower lobe to 15.3 percent in the left upper lobe. The subjects were grouped into simple categories based on the number of packs smoked per day and the pack-year history of smoking. Subjects who smoked more than two packs per day (n = 11) had the highest MI (37.4 +/- 4.9 percent, mean +/- SEM). Fifty-seven subjects smoked more than one pack per day but fewer than or equal to two packs per day, and they had a mean MI of 22.3 +/- 2.9 percent. Subjects who smoked one pack per day or less (n = 31) had a mean MI of only 12.9 +/- 2.8 percent. The MI of those who smoked more than two packs per day was significantly greater than the MI of those who smoked one pack per day or less (p < or = 0.003). While the MI varied from 12.9 +/- 3.5 percent in subjects who had smoked less than 20 pack-years to a maximum of 29.1 +/- 4.5 percent in those who had smoked greater than 60 pack-years, no statistically significant difference was detected between these two groups. Thus, we conclude that heavy tobacco use is associated with important alterations of bronchial mucosa. Furthermore, the intensity of tobacco use (packs per day) rather than the number of pack-years appears to be the more important factor in promoting squamous metaplasia of the bronchial mucosa. PMID- 8486023 TI - Intrathoracic adenopathy associated with pulmonary tuberculosis in patients with human immunodeficiency virus infection. AB - The role of computed tomography (CT) in the diagnosis of mediastinal tuberculous lymphadenitis was evaluated retrospectively in 25 human immunodeficiency virus (HIV)-infected patients (19 had AIDS). In all cases, the diagnosis of tuberculosis was established by mycobacterial culture and/or histologic evaluation. The most characteristic CT finding was the presence of low-density mediastinal and hilar lymph nodes in 16 of 19 (84 percent) patients with AIDS and four of six (67 percent) HIV-seropositive patients without AIDS. Marked enhancement of the periphery of nodes was identified in five cases, all in patients with documented AIDS. In most cases, lymphadenopathy proved to be massive, presenting as extensive, heterogenous soft-tissue lesions, presumably the result of coalescence of groups of matted nodes. We conclude that low-density mediastinal and/or hilar lymph nodes on CT, while not pathognomonic, is sufficiently characteristic for tuberculosis to warrant empiric antituberculosis therapy pending results of cultures. PMID- 8486024 TI - The tidal volume response to incremental exercise in COPD. AB - Patients with severe COPD often exhibit a ventilatory limit to exercise. This is associated with a shallow breathing pattern when compared with normal control subjects. It is unclear, however, what factors affect differences in breathing patterns within this patient population. To further investigate the tidal volume (VT) response to exercise in severe COPD, nine patients were recruited to undergo a maximal incremental exercise test. Pulmonary function tests, collection of expired gases, and continuous pulse oximetry were performed. As a group, the results were as follows (mean +/- SD): The FEV1 was 31 +/- 7 percent of predicted, the FRC was 143 +/- 18 percent of predicted, and the DCO was 47 +/- 15 percent of predicted. Exercise testing showed an oxygen consumption at peak exercise of only 44 +/- 9 percent predicted, a dyspnea index of 101 +/- 19 percent predicted, a heart rate at peak exercise of 75 +/- 12 percent predicted, a tidal volume at peak exercise (PKVT) of 1.23 +/- .35, a respiratory rate at peak exercise (PKfb) of 26 +/- 6, and an oxygen saturation at peak exercise (PKO2sat) of 96 +/- 4 percent. An anaerobic threshold (AT) occurred in seven of the nine patients at a mean of 31 +/- 8 percent predicted maximal oxygen consumption. Regression analysis showed the PKVT to be inversely correlated with the FEV1 (r = -0.76; p = 0.01) and the PKfb (r = -0.85; p = 0.003), while positively correlating with the FRC (r = +0.80; p = 0.01) and the PKO2sat (r = +0.69; p = 0.04). Additionally, there was a trend for the PKVT to be inversely related with the AT (r = -0.72; p = 0.06). In COPD, the more severe the obstruction and hyperinflation, the larger the VT response to exercise. This may serve to avoid a deleterious increase in autoPEEP by promoting a lengthening of the expiratory time. Furthermore, given the association of an earlier AT and a higher PKO2sat with a larger PKVT, this would suggest that such a response may minimize the effects of dead space and/or autoPEEP on O2 delivery (early AT). PMID- 8486025 TI - Bronchodilator delivery from Gentlehaler, a new low-velocity pressurized aerosol inhaler. AB - We have compared radioaerosol deposition pattern and bronchodilator response following inhalation of 100 micrograms of albuterol from a correctly used conventional metered dose inhaler (MDI) to those from Gentlehaler, a new compact low-velocity pressurized aerosol device (Schering Corporation), in a group of ten asthmatic patients (mean baseline FEV1 52 percent; reversibility > 15 percent). Whole lung deposition (mean 18.8 percent of dose by conventional MDI, mean 19.9 percent of dose by Gentlehaler), regional lung deposition, and bronchodilator response were similar for the two devices, but oropharyngeal deposition was halved by Gentlehaler. The spray velocity from Gentlehaler was less than 2 m s-1 compared with a velocity of greater than 30 m s-1 commonly found in the conventional device. Gentlehaler may therefore play a valuable role in inhalation therapy, notably by reducing "cold Freon" problems (respiratory inhibition) in pressurized aerosol delivery, and by reducing oropharyngeal losses of inhaled corticosteroids. PMID- 8486026 TI - Diagnosis of right atrial mass lesions by transesophageal and transthoracic echocardiography. AB - The echocardiographic findings by transesophageal and transthoracic techniques were compared in 16 patients with right atrial mass lesions diagnosed by transesophageal echocardiography. In only 8 of the 16 patients were the masses imaged by transthoracic echocardiography. Masses in the main body of the right atrium (three of five), as well as those associated with indwelling catheters and pacer wires (three of four) were more likely to be imaged by transthoracic echocardiography than masses in the right atrial appendage (zero of three) or in the superior or inferior vena cava (one of three). Associated masses in other cardiac chambers were detected by transthoracic echocardiography in three of six patients. Other features such as size, mobility, and site of attachment of right atrial masses in general were better defined by transesophageal echocardiography. Thus, patients with suspected right atrial masses should be investigated with transesophageal echocardiography. PMID- 8486027 TI - Prognostic significance of posturally induced crackles. Long-term follow-up of patients after recovery from acute myocardial infarction. AB - We found that on pulmonary auscultation, fine crackles could be induced by changing the posture from sitting to supine and/or from supine to supine with passive leg elevation in patients without obvious congestive heart failure. We named these crackles "posturally induced crackles (PIC)." To investigate the relationship between PIC and long-term prognosis after myocardial infarction, we followed up 262 patients who recovered from acute myocardial infarction for a mean period of six years. Cardiac death occurred in three of 78 PIC-negative patients and in 28 of 143 PIC-positive patients. PIC-negative patients had a significantly better long-term prognosis than PIC-positive patients according to the Kaplan-Meier survival curves for cardiac death (p < 0.01). In a multilogistic model based on 70 appropriate cases, PIC was the third most important prognosticator after recovery from myocardial infarction and the number of diseased coronary vessels and the pulmonary capillary wedge pressure ranked first and second, respectively. PMID- 8486028 TI - Surveys of long-term ventilatory support in Minnesota: 1986 and 1992. AB - To determine the prevalence and some characteristics of persons in Minnesota receiving long-term ventilatory support (ventilator-assisted individuals [VAIs]), we conducted a survey of this population in Minnesota in 1986 and then again in 1992 by canvassing long-term care units and home medical equipment providers. The number of VAIs in 1992 was 110 percent greater than in 1986 (216 vs 103). In 1986, 81 percent of these patients received care at home; the remaining patients were supported in long-term care facilities. By 1992, the percentage had changed to 65 percent supported in the home and 35 percent in long-term care facilities. In both surveys, the largest number of VAIs were in the diagnostic categories of poliomyelitis, cervical trauma, amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), and muscular dystrophy. The primary diagnoses with the greatest increase in number of patients were cervical trauma and ALS. When VAIs were categorized by age groups, there was a large increase in the proportion of patients younger than 10 years of age and older than 60 years of age. While the number of patients is small, the total resources required for care of these patients can be substantial. These data suggest that we need to monitor the number and demographic characteristics of VAIs in the United States so that appropriate policies and programs are developed to provide effective support services. PMID- 8486029 TI - Effects of obesity on respiratory resistance. AB - To assess the effects of obesity on pulmonary function, 46 healthy subjects exhibiting various degrees of obesity underwent lung function tests. Subjects were divided into three groups according to body mass index (BMI): 13 had minimal obesity (BMI, 25 to 29 kg/m2, group 1); 24 had a BMI in the 30 to 40 range (group 2); and 9 displayed to morbid obesity (BMI > 40, group 3). Respiratory resistance was estimated by the forced random noise oscillation technique and airway resistance was determined by body plethysmography. Lung volumes and expiratory flows were also determined and significant negative correlations with BMI were found. Expiratory flows diminished in proportion to lung volumes, and the ratio of forced expiratory volume in 1 s to forced vital capacity was within normal limits. Although expiratory flows did not suggest bronchial obstruction, both respiratory resistance and airway resistance rose significantly with the level of obesity (p < 0.005 and p < 0.025, respectively), from 3.2 (+/- 0.02) and 3.2 (+/- 0.02) cm H2O.s.L-1, respectively, in group 1, to 5.5 (+/- 0.06) and 5.0 (+/- 0.05), respectively, in group 3. Evaluation of the factors responsible for this increased resistance disclosed a significant linear correlation between airway conductance and functional residual capacity (r = 0.70, p < 10(-4)), but specific airway conductance was found to be independent of the degree of obesity. The difference between respiratory resistance and airway resistance did not widen significantly according to the level of obesity, suggesting that chest wall resistance was not a factor enhancing these resistances. Taken together, these findings suggest that in addition to the elastic load, obese subjects have to overcome increased respiratory resistance resulting from the reduction in lung volumes related to being overweight. PMID- 8486030 TI - Bronchial hyperreactivity in patients with moderate pulmonary circulation overload. AB - The clinical course of congestive heart failure (CHF) and mitral valve stenosis (MVS) is accompanied by episodes of dyspnea, wheezing, and cough, symptoms also observed in patients with bronchial hyperreactivity. However, it is still controversial whether bronchial hyperreactivity is demonstrable in patients with chronic overload of the pulmonary circulation. In order to examine the effects of CHF on the respiratory function, we performed pulmonary function tests, titrated bronchial acetylcholine provocations, and left and right heart catheterization in 21 patients with impaired left ventricular function (mean ejection fraction, 37 percent, NYHA class 3), 5 patients with MVS, and 17 control patients with coronary artery disease (mean ejection fraction, 63 percent). Bronchial hyperresponsiveness was defined as an obstructive response to increased doses of inhaled acetylcholine. A 20 percent fall in forced expiratory volume in the first second (FEV1), a 100 percent increase in total airway resistance (Rtot), and a 60 percent reduction of pulmonary conductance (SGtot) were considered positive. Patients with impaired left ventricular function showed significantly higher airway resistance, and lower airway conductance at the maximal tolerated acetylcholine dose compared with control patients. Patients with MVS had a significant lower airway conductance. The induced bronchial obstruction was completely reversible upon inhalation of a beta 2-mimetic. We conclude that chronic overload of the pulmonary circulation is accompanied by bronchial hyperreactivity that may augment the symptoms of dyspnea in patients with CHF and MVS. PMID- 8486031 TI - The bronchitis index. A semiquantitative visual scale for the assessment of airways inflammation. AB - Flexible fiberoptic bronchoscopy has been proven to be an effective tool for the assessment and characterization of airway inflammation. Visual inspection of airways affected by chronic bronchitis discloses an abnormal appearance characterized by erythema, edema, secretions, and friability. It was hypothesized that the visual appearance of airway inflammation could be assessed in a semiquantitative manner. A bronchitis index (BI) was developed that scores the visual appearance of airways according to the presence or absence of abnormal edema, erythema, secretions, and friability (0 = normal, 3 = remarkably abnormal). The BI was determined in three study groups: 86 subjects with chronic bronchitis, 15 subjects who smoked cigarettes, but did not have chronic bronchitis, and 25 normal, nonsmoking control subjects. The reproducibility of the BI was determined by comparing the results from pairs of two independent observers assessing 249 subjects undergoing fiberoptic bronchoscopy under various investigative protocols. In total, nine investigators scored the airways. For the three observer pairs with more than six observations, there were no differences noted in the BI (p = 0.43, 0.67, 0.82). To control for the effect of cough upon the BI, lidocaine usage was recorded. No correlation was found between lidocaine usage and BI. As previously noted for a smaller group of subjects, the BI was found to be elevated in those with chronic bronchitis (13.2 +/- 0.53) compared with both asymptomatic smokers (8.5 +/- 0.89, p < 0.0005) and normal volunteers (2.3 +/- 0.55, p < 0.0001); the latter two groups also differed significantly (p < 0.0001). The BI was also found to correlate significantly with bronchial sample lavage fluid neutrophil content in lavage fluid obtained after determination of the BI and with cigarette smoking as quantitated by pack years. Conversely, the BI correlated negatively with the spirometric measures of airway obstruction, FEV1, FEV1/FVC, FEV25-75, and FEFmax. Thus, the BI appears to be a reproducible, semiquantitative assessment of the visual appearance of airway inflammation. It may be a useful bronchoscopic adjunct for the assessment of airway inflammation in clinical investigations. PMID- 8486032 TI - "Pseudo auto-PEEP"? A new cause for discrepancy between the end-expiratory occlusion plateau pressure and airway opening pressure. AB - The purpose of this study is to describe an unexpected degree of differences between expiratory occlusion plateau pressure (EPO) and airway opening pressure (Pawo) measured level of intrinsic positive end-expiratory pressure above externally applied (auto-PEEP) that was found in six critically ill patients. In six patients (ten studies), the presence and degree of auto-PEEP found during the EPO maneuvers was not confirmed by Pawo measurements. In five studies, flow tracings showed prolonged near zero flow toward end expiration and a slow rise to plateau during the EPO maneuver. Because of the static nature of the EPO determination, a rise in pressure could conceivably be caused by the presence of subcutaneous or mediastinal emphysema and retrograde flow across the airway defect during exhalation. We suggest another cause for auto-PEEP-dynamic hyperinflation from extrapulmonary flow limitation. PMID- 8486033 TI - Aerobic and anaerobic microbiology of empyema. A retrospective review in two military hospitals. AB - The microbiology and clinical features of empyema were studied retrospectively in 197 patients whose specimens yielded bacterial growth after inoculation for aerobic and anaerobic bacteria. Three hundred forty-three organisms (216 aerobic or facultative and 127 anaerobic organisms) were isolated. Aerobic bacteria were isolated in 127 (64 percent) patients, anaerobic bacteria in 25 (13 percent), and mixed aerobic and anaerobic bacteria in 45 (23 percent). The predominant aerobic or facultative organisms were Streptococcus pneumoniae (70 isolates), Staphylococcus aureus (58), Escherichia coli (17), Klebsiella pneumoniae (16), and Haemophilus influenzae (12). The predominant anaerobes were pigmented Prevotella and Porphyromonas species (24), Bacteroides fragilis group (22), anaerobic cocci (36), and Fusobacterium species (20). beta-Lactamase-producing organisms were recovered in 49 (38 percent) of 128 tested specimens. These included all 42 tested S aureus and 15 B fragilis group, 4 of 9 K pneumoniae, 3 of 9 H influenzae, 3 of 8 pigmented Prevotella and Porphyromonas species, and 2 of 6 E coli. Most patients from whom S pneumoniae and H influenzae were recovered had pneumonia, and most patients with S aureus had pneumonia, aspiration pneumonia, and lung abscesses. The recovery of anaerobic bacteria was mostly associated with the concomitant diagnosis of aspiration pneumonia, and lung, subdiaphragmatic, dental, and oropharyngeal abscesses. These data highlight the importance of anaerobic bacteria in selected cases of empyema. PMID- 8486034 TI - Early and rapid diagnosis of perioperative myocardial infarction in aortocoronary bypass surgery by immunoturbidimetric myoglobin measurements. AB - STUDY OBJECTIVES: To evaluate measurements of myoglobin in the diagnosis of perioperative myocardial tissue damage in aortocoronary bypass surgery. A new immunoturbidimetric myoglobin assay, which yields quantitative concentrations of myoglobin within approximately 1 min, was used. DESIGN: Prospective clinical study. PATIENTS: Thirty-two patients scheduled for elective aortocoronary bypass surgery. MEASUREMENTS AND RESULTS: Myoglobin concentrations in patients without perioperative myocardial infarction (n = 27) increased with aortic unclamping, peaked after 1 h, and decreased to almost baseline values within 4 h. By contrast, myoglobin concentrations in patients with perioperative myocardial infarction (n = 5) further increased after 1 h of aortic unclamping and were significantly higher (p < 0.05) than in patients without myocardial infarction as soon as 3 h after aortic unclamping. In all patients with myocardial infarction, myoglobin concentrations exceeded 400 micrograms/L over a minimum period of 4 h. Ten of 27 patients without perioperative myocardial infarction had episodes of minor perioperative myocardial ischemia (defined as ST-T segment changes in the ECG without a concomitant increase in the activity of creatine kinase isoenzyme MB). Myoglobin concentrations (but not creatine kinase isoenzyme MB activity) were significantly higher in these 10 patients when compared to the 17 completely uneventful cases. CONCLUSIONS: Plasma concentrations of myoglobin are a sensitive marker of perioperative myocardial tissue damage in aortocoronary bypass surgery. Myoglobin measurements with the immunoturbidimetric assay have an important contribution to make to the early and rapid diagnosis of perioperative myocardial infarction. PMID- 8486035 TI - Closure of the patent ductus arteriosus with a Ligaclip through a minithoracotomy. AB - This article describes a technique which allows the patent ductus arteriosus (PDA) to be closed through a minithoracotomy. It combines a simple method of inducing atelectasis with Ligaclip closure of the PDA through a subaxillary incision. It was used successfully in 11 children and adolescents. PMID- 8486036 TI - A clinical study of intravenous cibenzoline in selected patients with recent onset atrial tachyarrhythmia. AB - Twenty-five adult patients with sustained atrial tachyarrhythmia (ATA) and without heart failure were treated by intravenous cibenzoline, 1 mg/kg, as a slow bolus infusion, followed by a 8 mg/kg/24 h continuous infusion. Sinus rhythm conversion was observed in 18 patients (72 percent success rate). Severe adverse cardiac events were observed in only one patient (4 percent occurrence rate), as a wide QRS complex tachycardia finally requiring a semiemergency direct-current cardioversion. Two minor side effects were additionally observed. A similar population of 21 patients was conventionally treated with amiodarone, either given intravenously, 15 to 20 mg/kg/24 h, or orally, 30 mg/kg/24 h as a single dose. An identical success rate (15/21; 71 percent) was observed. Our results indicate that in selected patients with ATA, cibenzoline and amiodarone are highly effective for producing sinus rhythm conversion. We suggest that the former drug may be used as a first-line treatment. In case of failure, the latter may constitute an alternative to transthoracic electrical countershock. PMID- 8486037 TI - Differential lobe lavage for diagnosis of acute Pneumocystis carinii pneumonia in patients receiving prophylactic aerosolized pentamidine therapy. AB - The diagnostic yield of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus has been reported to be 95 percent, but falls to 62 percent in patients receiving aerosolized pentamidine. Because aerosolized pentamidine appears to be preferentially deposited in the middle and lower lobes, we postulated that an upper lobe lavage would have a higher diagnostic yield than the standard middle/lower lobe lavage in patients receiving aerosolized pentamidine. Twenty five patients receiving aerosolized pentamidine suspected of having acute PCP underwent separate BAL of an upper lobe and lower lobe as well as transbronchial biopsy. Fifteen of the 25 (60 percent) were diagnosed as having PCP. Of the 15, one had the samples inadvertently combined. In the remaining 14, BAL was positive for P carinii organisms in 12 lavages of the lower lobe and 14 of the upper lobe. Upper lobe lavage had statistically significantly more P carinii organisms by semiquantitative technique than the lower lobe. In patients receiving aerosolized pentamidine, who develop acute PCP, an upper lobe lavage may have a higher diagnostic yield than the standard middle/lower lobe lavage. In addition, the transbronchial biopsy specimen offered no treatable diagnosis that was not made by lavage alone in the 25 patients. This raises the question of the utility of transbronchial biopsies in these patients. PMID- 8486038 TI - Measuring self-efficacy expectations for the self-management of cystic fibrosis. AB - This research developed and determined the psychometric characteristics of a measure of self-efficacy expectations (a social cognitive theory construct) for the self-management of cystic fibrosis (CF). Items for the original instrument were sampled from 150 self-management performance objectives for CF that represented behaviors in eight domains of CF care, including aspects of medical care, coping, and communication. The instrument was administered to 199 parents of children and adolescents with CF from two CF centers. The findings support a multidimensional structure for self-efficacy consistent with the multiple types of behavior required for the management of a chronic illness such as CF. An alpha factor analysis yielded solutions clearly reflecting five theorized aspects of self-management: medical judgment and communication, coping, family communication, compliance, and acceptance. The first factor of the caretaker's scale most closely represents the underlying conceptualization of self-management as requiring self-monitoring of health status and collaboration with the health care provider in making judgments about treatment. The unit weighted factors exhibited high internal consistencies (Cronbach's alpha-factors ranging from 0.73 to 0.88). PMID- 8486039 TI - Angiosarcoma in the lung. AB - Angiosarcoma involving the lung is a rare disorder and its clinical features are not well known. We conducted a retrospective analysis of 15 patients seen at our institution from 1950 to 1990 in an attempt to better characterize the spectrum of clinical and radiographic findings of angiosarcoma in the lung. No documented case of primary angiosarcoma of the lung was seen. The diagnosis of metastatic angiosarcoma to the lung was made antemortem in 12 of 15 cases, either by lung biopsy specimen (5 patients), biopsy evidence of metastatic disease elsewhere with abnormal chest radiograph (4 patients), or a compatible clinical picture in a patient with previously documented angiosarcoma arising in an extrapulmonary site (3 patients). The median age at the time of diagnosis was 45 years with the most common presenting symptom being hemoptysis (7 of 15 patients). Other presenting complaints included weight loss (6 of 15), cough (4 of 15), and chest pain (4 of 15) occurring 6 weeks to 1 year prior to diagnosis. Chest radiographs frequently disclosed multiple pulmonary nodules (11 of 15). Primary origins of the angiosarcoma most commonly included the heart and breast. Metastatic sites other than the lung included the pericardium, liver, spleen, kidney, adrenal gland, bone, and brain. The prognosis is generally poor, with our study population surviving an average of 9 months after diagnosis. PMID- 8486040 TI - Time course of hemostatic abnormalities in sepsis and its relation to outcome. AB - OBJECTIVES: To investigate the time course and the relation to prognosis of coagulation and fibrinolytic abnormalities in patients with septic shock. PATIENTS AND METHODS: Forty-eight consecutive patients admitted to the medical ICU with the diagnosis of septic shock (diagnosed by defined criteria) were studied. Mortality was 25 of 48. Mean age was 57 +/- 7.3 years. Blood samples were obtained on days 1, 4, and 7 after hospital admission to measure tissue-type plasminogen activator antigen (t-PA), urokinase-type plasminogen activator (u PA), plasminogen activator inhibitor antigen (PAI-1), plasminogen, alpha 2 antiplasmin, fibrinogen, antithrombin III, protein C, protein S, thrombin antithrombin complexes (TAT), D-dimer, and von Willebrand factor-related antigen (vWF:Ag). RESULTS: All patients showed marked abnormalities in both the coagulation and fibrinolytic systems. There were signs of coagulation activation and elevation of both activators and inhibitors of fibrinolysis. Nonsurvivors showed lower levels of protein C and antithrombin III and higher concentration of TAT than survivors. While both t-PA and PAI-1 concentrations were high in survivors and nonsurvivors, only survivors showed a progressive normalization of both parameters during the study period. Low plasminogen levels and plasminogen/alpha 2-antiplasmin ratio were found in both groups, presenting a trend toward normalization only in survivors. The differences reported were not apparent at the time of hospital admission. CONCLUSIONS: Septic shock is characterized by coagulation activation and fibrinolysis activation and inhibition. Nonsurvivors present a particular hemostatic profile characterized by a more marked activation of coagulation and a more intense inhibition of fibrinolysis. None of the abnormalities studied was significantly different between survivors and nonsurvivors at the time of hospital admission. In the presence of fibrin formation, nonsurvivors present a maintained imbalance in the fibrinolytic response determined by higher PAI-1 plasma concentration, probably contributing to their poor outcome. PMID- 8486041 TI - Effect of air-supported, continuous, postural oscillation on the risk of early ICU pneumonia in nontraumatic critical illness. AB - STUDY OBJECTIVES: We hypothesized that continuous, automatic turning utilizing a patient-friendly, low air loss surface would reduce the incidence of early ICU pneumonia in selected groups of critically ill medical patients. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Medical ICU of a large community teaching hospital. PATIENTS: One hundred twenty-four critically ill new admissions to the medical ICU at Charity Hospital in New Orleans. INTERVENTIONS: Patients were prospectively randomized within one of five diagnosis-related groups (DRG)--sepsis (SEPSIS), obstructive airways disease (OAD), metabolic coma, drug overdose, and stroke--to either routine turning on a standard ICU bed or to continuous turning on an oscillating air-flotation bed for a total of five days. MEASUREMENTS AND RESULTS: Patients were monitored daily during the treatment period for the development of pneumonia. The incidence of pneumonia during the first five ICU days was 22 percent in patients randomized to the standard ICU bed vs 9 percent for the oscillating bed (p = 0.05). This treatment effect was greatest in the SEPSIS DRG (23 percent vs 3 percent, p = 0.04). Continuous automatic oscillation did not significantly change the number of days of required mechanical ventilation, ICU stay, hospital stay, or hospital mortality overall or within any of the DRGs. CONCLUSIONS: We conclude that air supported automated turning during the first five ICU days reduces the incidence of early ICU pneumonia in selected DRGs; however, this form of automated turning does not reduce other measured clinical outcome parameters. PMID- 8486042 TI - Critical illness in pregnancy. An analysis of 20 patients admitted to a medical intensive care unit. AB - There is a paucity of literature with regard to the need for intensive care treatment of critically ill obstetric patients. In this review, the findings from 20 obstetric patients admitted to a medical ICU (MICU) over a 40-month period were analyzed. Demographics, preexistent medical problems, diagnoses, days in the hospital and the MICU, need for mechanical ventilation, maternal and fetal mortality, and invasive procedures were reviewed. (For comparison, a limited analysis of nonobstetric admissions to the MICU over the same time period were included.) Fifty percent (10) of the patients had preexisting medical problems. Maternal mortality was 20 percent (4 patients), with a fetal mortality of 35 percent (7). In all of the maternal deaths, adult respiratory distress syndrome was present. Although mortality and the need for mechanical ventilation did not differ between the obstetric and nonobstetric patients, pulmonary artery and arterial catheters were placed at a higher rate in the obstetric patients. Critically ill obstetric patients, although younger than general MICU patients, appear to have as great a risk of dying of their critical illness and have a high infant mortality. PMID- 8486043 TI - Strategy for diagnosis of patients with suspected acute pulmonary embolism. AB - STUDY PROTOCOL: Two separate groups of clinical investigators have provided new information and divergent approaches to the management of acute pulmonary embolism (PE). In this position paper, investigators from both groups (Prospective Investigation of Pulmonary Embolism Diagnosis [PIOPED] and Canadian study groups) have utilized the combined scientific database in order to rationalize seemingly polarized diagnostic recommendations into a single practical algorithm. METHODS: An in-depth review established the relative risks of deep venous thrombosis (DVT) and the related accuracy of diagnostic tests. In PIOPED, 640 of 887 patients at risk for PE had either an intermediate probability ventilation/perfusion (V/Q) scan or a V/Q scan probability that was discordant with the prior estimate of probability by clinical assessment. The risk of PE in these patients was 16 to 88 percent (average, 34 percent). In this group, we calculated the probability of PE assuming that tests for DVT had been performed and that 50 percent of patients with PE have detectable proximal DVT. By calculation, 108 in 640 patients of whom the diagnosis of PE was uncertain, would have shown proximal DVT. In 239 of these 640 patients, tests for DVT would have been negative and the risks of PE in these patients is calculated to be less than 10 percent. RESULTS: Therefore, we calculate that in 347 of 640 patients, confident recommendations for treatment or no treatment could have been given without pulmonary angiography. Accordingly, in the PIOPED study group of 887 patients, the need for pulmonary angiography would have been reduced from 640 (72 percent) to 293 patients (33 percent). CONCLUSION: In conclusion, a diagnostic strategy that includes the clinical evaluation, V/Q scan, and evaluation for DVT would decrease the number of patients who require pulmonary angiography from 72 to 33 percent. PMID- 8486044 TI - Obstacles to discharge of ventilator-assisted children from the hospital to home. AB - Home care for ventilatory-assisted children improves psychosocial development and reduces medical costs compared with hospital care; yet, many ventilator-assisted children remain hospitalized for lengthy periods of time after they have achieved medical stability. To identify factors that contributed to a delay in hospital discharge from the time medical stability was achieved, we reviewed the records of 54 ventilator-assisted children (age 4.6 +/- 5.9 [SD] years at discharge) who were discharged from the hospital on a regimen of home mechanical ventilation. The length of the hospitalization from which the ventilator-assisted children were initially discharged on the ventilator was 172 +/- 161 days (range, 2 to 756). The time from medical stability to discharge was 118 +/- 144 days (range, 2 to 724), or 73 percent +/- 29 percent of the total hospitalization. Fifty-one ventilator-assisted children were discharged to their natural parents' homes, and three were discharged to foster care. Once ventilator-assisted children were medically stable, it took 99 +/- 141 days for third-party payers to approve home care funding, and only 48 +/- 87 days to be discharged once funding was approved. For the 27 ventilator-assisted children with public funding, it took 184 +/- 177 days for home care funding approval, compared with 52 +/- 43 days for the 27 ventilator-assisted children with private funding (p < 0.001). Parent training took only 52 +/- 65 days. It took 369 +/- 334 days (range, 44 to 711 days) to find placement for the three ventilator-assisted children who were placed in medical foster care. In summary, ventilator-assisted children often remained hospitalized for prolonged periods of time, after they were medically stable, for nonmedical reasons. The greatest obstacle to hospital discharge was seeking approval for home care funding and for arranging out-of-home placement. Public funding agencies took significantly longer to approve home care funding than private insurance agencies. PMID- 8486045 TI - Management of lung transplant rejection. AB - Using current immunosuppressive protocols, rejection is common after lung transplantation. Most recipients have at least one episode of acute rejection, and approximately 25 percent of recent long-term survivors have developed chronic rejection. Acute rejection has usually been reversible with treatment, but chronic rejection has responded poorly, relapsed frequently, and been one of the leading causes of late morbidity and mortality. Appropriate management of rejection is predicated on timely, accurate diagnosis. Clinical criteria for the diagnosis of acute rejection are useful but nonspecific, and TBB has emerged as the procedure of choice for diagnosing acute rejection and infection. Chronic rejection is manifested by OB and is characterized physiologically by the development of airflow obstruction. Although histologic confirmation is preferable, the sensitivity of TBB for the detection of OB has been inconsistent, and the specificity has been low. Lung transplantation has indeed come of age, but understanding the immunopathogenesis and improving the clinical management of rejection remain major challenges for the next decade. PMID- 8486046 TI - Anterior mediastinal mass. PMID- 8486047 TI - Weight loss, hemoptysis, diffuse alveolar infiltrates and hemorrhagic cerebral lesions in a 57-year-old man. PMID- 8486048 TI - Pathophysiology of ovine smoke inhalation injury treated with extracorporeal membrane oxygenation. AB - An ovine model was used to study the pathophysiology of smoke inhalation injury treated with extracorporeal membrane oxygenation (ECMO). Smoke inhalation is characterized by leukocyte-oxygen free-radical mediated acute lung injury. Treatment with ECMO was by extracorporeal venoarterial or venovenous perfusion using a venous drainage reservoir, roller pump, heat exchanger, and membrane lung oxygenator capable of oxygen delivery to and carbon dioxide removal from a patient. Blood-foreign surface interactions are known to occur during ECMO. We examined the effects of ECMO on circulating leukocytes, oxygen free-radical activity, thromboxane release, and gas exchange after smoke inhalation injury. Animals treated with smoke and ECMO had significantly increased circulating thromboxane B2 levels and oxygen free-radical activity compared with sham-treated animals and animals treated with smoke and mechanical ventilation (MV). Likewise, there was a significant increase in lung wet-to-dry weight ratios in animals treated with smoke and ECMO compared with those treated with smoke and MV. These data may account for the initial deterioration in native lung function after the initiation of ECMO and imply that ECMO may potentiate the pathophysiology of smoke inhalation injury. PMID- 8486049 TI - Ball-valve thrombus obstructing a bioprosthetic mitral valve. AB - We present a patient with a large, left atrial ball valve thrombus that was intermittently obstructing a bioprosthetic mitral valve. The diagnosis was confirmed by transesophageal two-dimensional echocardiogram. The transthoracic study initially had failed to demonstrate the true ball valve nature of the thrombus and instead, suggested two separate mass lesions, one in the left atrium and one in the bioprosthetic mitral valve. PMID- 8486050 TI - Spontaneous echo contrast in massive pericardial effusion with tamponade. AB - Spontaneous echo contrast is uncommon in pericardial effusion. We report the case of a patient with massive malignant pericardial effusion causing cardiac tamponade in which the intense spontaneous echo contrast was found in the effusion by echocardiography. It was suggested that both the heavy blood content and a large amount of pericardial effusion were needed to create the phenomenon of spontaneous echo contrast in the pericardial cavity. PMID- 8486051 TI - Right-sided pneumothorax as a result of a left-sided chest tube. AB - Chest tubes are inserted for a variety of reasons, and a number of complications have been associated with their use. We report a case of traumatic hemopneumothorax in which the chest tube crossed the mediastinum into the contralateral lung causing a pneumothorax. Its position was not apparent on portable chest radiographs. PMID- 8486052 TI - Traumatic aortic valve injury sustained despite the deployment of an automobile air bag. AB - Blunt chest trauma is a rare cause of aortic valve dysfunction. A case of the successful management of traumatic injury to the aortic valve is reported. The aortic valve injury was sustained in an automobile accident despite the use of a seat belt and the deployment of an air bag. The literature is briefly reviewed. Aortic valve injury remains a consideration in cases of automobile-associated chest trauma, even in automobiles equipped with seat belts and air bags. PMID- 8486053 TI - Tension pyopneumothorax. Rare presentation of ruptured Barrett's esophagus. AB - Tension pneumothorax following esophageal rupture is very rare. We report a case in which a perforated Barrett's esophagus rapidly developed a spontaneous tension pyopneumothorax. The mechanism for the tension remains obscure. Knowing that a tension pneumothorax can occur with esophageal rupture can help prevent misdiagnosis. PMID- 8486054 TI - Pneumomediastinum caused by subcutaneous emphysema in the shoulder. A rare complication of arthroscopy. AB - Severe subcutaneous emphysema following arthroscopy of the shoulder developed in a 62-year-old man. It subsequently evolved into pneumomediastinum with respiratory distress, but the patient recovered spontaneously. To our knowledge, this constitutes the first report of pneumomediastinum caused by subcutaneous emphysema in the shoulder. PMID- 8486055 TI - Myocarditis as a cause of primary right ventricular failure. AB - Patients with cardiomyopathy secondary to inflammatory myocarditis usually present with biventricular signs and symptoms. On occasion, the disease may progress focally, with left ventricular involvement predominating. This patient had elevated neck veins, edema, and a dilated right ventricle in the absence of left ventricular abnormalities. At autopsy, diffuse, transmural fibrosis of the right ventricle was found, consistent with end-stage myocarditis, with minimal disease of the left ventricle. This case emphasizes that the clinical manifestations of myocarditis can be limited to the right ventricle and should be considered in the differential diagnosis of right ventricular failure. PMID- 8486056 TI - Relationship of nasal continuous positive airway pressure to periodic limb movement disorder in a patient without sleep apnea. AB - The treatment of sleep apnea with nasal continuous positive airway pressure (CPAP) occasionally has been associated with the appearance of periodic limb movement (PLM) disorder, but it has not been clear whether CPAP induces PLM, or whether the PLM is simply disguised until apnea is treated. We report the emergence of PLM after the inadvertent application of CPAP in a patient without sleep apnea. PMID- 8486057 TI - Disappearing intracardiac thrombi in both atria after mumps in a patient with Turner syndrome. AB - A girl with Turner syndrome was admitted with an acute cerebrovascular occlusive disease 15 days after mumps infection. Imaging techniques such as Doppler echocardiography, computed tomography and angiography of the heart revealed the existence of masses in both atria. Eight days after the last radiologic study the patient had an operation, but no masses were found in either atrium. It was thought that atrial thrombi, probably formed after viral infection, had broken down to form emboli and disappeared. It is proposed that the patients with congenital cardiopathy should be regularly examined after viral infections for possible intracardiac thrombus formation. If such a mass is found and the decision is to operate, the existence of the mass must be confirmed even in the operating room just before intervention. PMID- 8486058 TI - Agenesis of the right upper lobe. AB - Bronchoscopy and bronchography revealed a very rare abnormality in the embryonal anatomy of the right bronchial tree in a 54-year-old woman with cough. There was a proximal migration of the apical branch of the right upper bronchus toward the trachea and a distal migration of the two other branches toward the middle lobe bronchus. The proximal migration was accompanied by a narrowing of the trachea. This case is considered an extremely rare embryonal variation in the development of the right bronchial tree. PMID- 8486059 TI - Usefulness of inhaled high-dose corticosteroids in allergic bronchopulmonary aspergillosis. AB - Two patients with allergic bronchopulmonary aspergillosis were seen on a regular basis, one since 1978 and the other since 1982. Throughout this period, both subjects required daily oral administration of corticosteroids (between 15 and 40 mg of prednisolone daily) to control their symptoms and the lung infiltrates on the chest x-ray film. Attempts to further decrease the dosage of steroids or to discontinue their use were met with immediate recurrences of manifestations of the disease. With the introduction of high-dose inhaled beclomethasone dipropionate, both subjects could be weaned from their oral steroids and maintained with inhaled steroids alone for up to 11 months. We conclude that inhaled corticosteroids may be useful in the treatment of allergic bronchopulmonary aspergillosis. PMID- 8486060 TI - Transesophageal echocardiographic diagnosis of anomalous left coronary artery from the right aortic sinus. AB - Patients with anomalous left main coronary artery arising from the right sinus of Valsalva and coursing posteriorly between the aorta and the pulmonary artery are prone to sudden death. We present a patient with this entity in whom the diagnosis was made by transesophageal two-dimensional echocardiography and coronary angiography. PMID- 8486061 TI - Unusual complication of retrograde coronary sinus perfusion with pulmonary artery catheter. AB - A balloon-tipped catheter placed in the coronary sinus is used during cardiac surgery for retrograde cardioplegia and is secured by a purse string suture placed proximal to the atrioventricular groove in the lower right atrium. We report a complication of this procedure where a pulmonary artery catheter was sutured to the wall of the right atrium by the purse string suture in a patient scheduled for aortocoronary bypass grafting. Pulsatile resistance was noted when we attempted to withdraw the catheter indicating an attachment to the heart. The pulmonary artery catheter within the vascular space after atrial cannulation should be checked since the sheath-protected cannula will enable free mobility. PMID- 8486062 TI - Pleural effusion masquerading as myocardial infarction. AB - The effects of pleural effusions on the ECG have not been well studied. We report herein the case of a patient with extreme QRS axis deviation mimicking acute myocardial infarction. Thoracentesis caused the return of a more normal axis. PMID- 8486063 TI - Bronchiolitis obliterans organizing pneumonia. An unusual cause of solitary pulmonary nodule. AB - Bronchiolitis obliterans organizing pneumonia (BOOP) is a pulmonary disorder with a wide spectrum of radiologic features. Usually, these are bilateral, patchy, alveolar, or ground-glass infiltrates, but other presentations have also been described. We present a case in which the radiologic appearance was a cavitated pulmonary solitary nodule. We think that this finding may justify the inclusion of BOOP in the differential diagnosis of the pulmonary solitary nodule. PMID- 8486064 TI - Wegener's granulomatosis presenting as right middle lobe obstruction. AB - Wegener's granulomatosis may present with a variety of findings and be difficult to diagnose. We report a case of a 55-year-old woman presenting with right middle lobe obstruction who was found to have limited Wegener's granulomatosis. Extensive medical evaluation was nondiagnostic and open lung biopsy specimens were required to establish the diagnosis. PMID- 8486065 TI - Measles pneumonia. Treatment of a near-fatal case with corticosteroids and vitamin A. AB - A 29-year-old woman experienced overwhelming rubeola pneumonia requiring endotracheal intubation and mechanical ventilation. Treatment with high-dose corticosteroids and vitamin A was accompanied by a prompt clinical response. Further investigation of this novel therapy is needed. PMID- 8486066 TI - Mycetoma within an intralobar sequestration. Evidence supporting acquired origin for this pulmonary anomaly. AB - A rare example of an intralobar sequestration (ILS) containing a fungal mycetoma is reported. This finding indicates the presence of a communication between the ILS and the airways, thus supporting the theory that ILSs are acquired lesions, rather than congenital malformations. PMID- 8486067 TI - Adult respiratory distress syndrome as a complication of postanginal sepsis. AB - Adult respiratory distress syndrome (ARDS) was described in 1971 by Petty and Ashbaugh. Since that time it has been reported in association with many disease entities. We report a case in which a patient with postanginal sepsis, also known as Lemierre's syndrome, had development of ARDS. PMID- 8486069 TI - Pulmonary artery sarcoma mimicking pulmonary embolism. AB - Two cases of primary pulmonary sarcoma which were initially diagnosed as pulmonary thromboembolism are presented. The clinical and radiologic features of pulmonary sarcoma are reviewed, with special emphasis on the features which distinguish it from thromboembolism. PMID- 8486068 TI - Flow velocity paradoxus and pulsus paradoxus in obstructive sleep apnea syndrome. AB - Echo-Doppler monitoring was performed simultaneously with two-dimensional and M mode echocardiography, polysomnography and blood pressure recording in an obstructive sleep apnea patient. Increase in tricuspid flow and decrease of mitral flow velocity was demonstrated during each diastole prior to pulsus paradoxus, while aortic flow velocity decreased with pulsus paradoxus during obstructed breathing during sleep. PMID- 8486070 TI - Antithrombotic therapy for venous thromboembolism. PMID- 8486071 TI - Risk of aspiration pneumonia in the elderly. PMID- 8486072 TI - Community-acquired pneumonia in the Far East. PMID- 8486073 TI - Thrombolytic therapy for pulmonary embolism. PMID- 8486074 TI - Selective bronchial intubation for the treatment of bronchopleural fistula in a preterm newborn. PMID- 8486076 TI - Detection of minimal amounts of DNA by electron microscopy using simplified spreading procedures. AB - Electron microscopic examination of nucleic acids requires the use of special spreading techniques. The classical method was developed by Kleinschmidt and Zahn in 1959. Modifications of this method increased sensitivity to allow detection of a total amount of about 1 x 10(-3) micrograms of single-stranded DNA and 2 x 10( 5) micrograms of double-stranded DNA. Here we describe two rapid and simple procedures increasing sensitivity by 1-2 orders of magnitude to visualize at least 1 x 10(-5) micrograms of single- and/or double-stranded DNA. PMID- 8486075 TI - Transcriptional regulation in Drosophila during heat shock: a nuclear run-on analysis. AB - We used a nuclear run-on assay as a novel approach to study the changes in transcriptional activity that take place in Drosophila melanogaster during heat shock. In response to a rapid temperature upshift, total transcriptional activity in cultured KC161 cells decreased proportionally to the severity of the shock. After extended stress at 37 degrees C (15 min or more), transcription was severely reduced, and at 39 degrees C most transcription was instantaneously arrested. However, strikingly different responses were observed for individual genes. Transcription of histone H1 genes was severely inhibited even under mild heat shock conditions. Transcription of the actin 5C gene decreased progressively with increasing temperature, while transcription of the core histone genes or of the heat shock cognate genes was repressed only under severe heat shock conditions. Transcriptional activation of the D. melanogaster heat shock genes was also investigated. In unshocked cells, hsp84 was moderately transcribed, while transcriptional activity at the other protein-coding heat shock genes was undetectable (less than 0.2 polymerases per gene). Engaged but paused RNA polymerase molecules were found at the hsp70 and hsp26 genes, but not at the other heat shock genes. The rates of transcription increased with increasing temperature with a peak of expression at around 35 degrees C. At 37 degrees C, induction was less efficient, and no induction was achieved after a rapid shift to 39 degrees C. Increased transcription of the heat shock genes was observed within 1-2 min of heat shock, and maximal rates were reached within 2-5 min. Despite very similar profiles of response, different heat shock genes were transcribed at strikingly different rates, which varied over a 20-fold range. The noncoding heat shock locus 93D was transcribed at a very high rate under non-heat shock conditions, and showed a transcriptional response to elevated temperatures different from that of protein-coding heat shock genes. An estimation of the absolute rates of transcription at different temperatures was obtained. PMID- 8486077 TI - A combined molecular and cytogenetic approach to genome evolution in Drosophila using large-fragment DNA cloning. AB - Methods of genome analysis, including the cloning and manipulation of large fragments of DNA, have opened new strategies for uniting molecular evolutionary genetics with chromosome evolution. We have begun the development of a physical map of the genome of Drosophila virilis based on large DNA fragments cloned in bacteriophage P1. A library of 10,080 P1 clones with average insert sizes of 65.8 kb, containing approximately 3.7 copies of the haploid genome of D. virilis, has been constructed and characterized. Approximately 75% of the clones have inserts exceeding 50 kb, and approximately 25% have inserts exceeding 80 kb. A sample of 186 randomly selected clones was mapped by in situ hybridization with the salivary gland chromosomes. A method for identifying D. virilis clones containing homologs of D. melanogaster genes has also been developed using hybridization with specific probes obtained from D. melanogaster by means of the polymerase chain reaction. This method proved successful for nine of ten genes and resulted in the recovery of 14 clones. The hybridization patterns of a sample of P1 clones containing repetitive DNA were also determined. A significant fraction of these clones hybridizes to multiple euchromatic sites but not to the chromocenter, which is a pattern of hybridization that is very rare among clones derived from D. melanogaster. The materials and methods described will make it possible to carry out a direct study of molecular evolution at the level of chromosome structure and organization as well as at the level of individual genes. PMID- 8486078 TI - Non-uniform distribution of methylatable CCGG sequences on human chromosomes as shown by in situ methylation. AB - We carried out in situ methylation of human chromosomes with the HpaII methylase using [3H]methyl-S-adenosyl-L-methionine as the methyl group carrier. Autoradiographs localising [3H]methyl groups show methylatable CCGG sequences in the R-bands as well as in the short arms of the acrocentric chromosomes that include ribosomal DNA. The strongest labelling was observed over a subset of R bands, including T-bands. Since methylatable CCGG sequences are representative of the unmethylated fraction of DNA, we suggest that differences in the degree of DNA methylation could be involved in the structure and function of chromosomal bands. PMID- 8486079 TI - Repetitive DNA sequence families in Crepis capillaris. AB - Three families of tandemly repetitive DNA from Crepis capillaris were cloned and characterized. Data obtained from in situ hybridization indicate that these families are located mainly in the heterochromatic C-bands. The pCcH32 family hybridizes at the paracentromeric C-band of the NOR (nucleolus-organized region) chromosome and along most of the long arm of the same chromosome. The pCcD29 family is located in all the remaining C-bands of the karyotype, while the third family, pCcE9, is restricted to the more proximal C-bands. Nucleotide sequence comparisons between one cloned repeating unit from each DNA family showed some significant regions of homology between the families. We discuss the sequence relationships between the three DNA families and the significance of our data in relation to models of heterochromatin evolution, emphasizing the concepts of equilocality and the differentiation of the NOR-bearing chromosome. We also examine the possible role that chromosome disposition, in either mitotic or meiotic nuclei, plays in the distribution and homogenization of heterochromatic DNA sequences. PMID- 8486080 TI - Binding of sequences from the 5'- and 3'-nontranscribed spacers of the rat rDNA locus to the nucleolar matrix. AB - Nucleolar matrix structures were obtained under different extraction conditions from highly purified isolated nucleoli. Their ultrastructural appearance, protein composition and capacity to bind rDNA preferentially were studied in a model binding system. A region spanning approximately 25 kb in the rat ribosomal gene locus was screened for DNA sites capable of specifically interacting with the proteins of the nucleolar matrix (MARs). Two such sites were identified: one is located on an EcoRV-KpnI fragment in the 5'-nontranscribed spacer region, between two repetitive elements and close to the transcription initiation site; the other MAR is on a PvuII-BamHI fragment located in the 3'-nontranscribed region, encompassing an element 85% homologous to a B2-sequence. The two MARs are located in regions rich in polypyrimidine/polypurine tracks and contain a few elements homologous to the consensus sequence for topoisomerase II. This indicates that the "attachment sites" for the ribosomal genes belong to the same class of sequences as the MARs attaching the chromosomal DNA to the nuclear matrix. PMID- 8486081 TI - Preliminary note: dangerous use of anticholinergic drugs in Brazil. AB - To better evaluate the non-medical use of anticholinergic substances in Brazil, a review of the local literature was performed. Synthetic compounds such as triexyphenidyl (Artane), benactizine (Asmosterona), dicyclomine (Bentyl) as well as Datura sp. tea were reported as being used by first and second grade students and by street children of several Brazilian cities. In several cases the percentage of youngsters indulging in such use was higher than the percentage found for cocaine, barbiturates, cough syrups and amphetamine-related drugs. Several cases of patients seeking treatment for dependence or for acute psychotic symptoms were also described. PMID- 8486082 TI - Correlates of heavy drinking and alcohol related problems among men and women in drug treatment programs. AB - A series of analyses were conducted to explore if there were significant differences in heavy drinking and alcohol-related problems in clients admitted to different types of drug treatment programs and whether such differences, if found, could be attributed to variation in social characteristics, drug use behavior, drinking norms, drinking contexts, or in reasons for combining alcohol and drug use. Men and women (N = 246) in four types of publicly funded treatment programs were interviewed at intake regarding drinking and drug use patterns and related problems. The results of the study showed significant differences in drinking behavior and alcohol-related problems of clients in different treatment modalities. Men in a county jail substance abuse program exhibited the highest frequency of heavy drinking and highest rates of alcohol problems; clients of methadone programs reported the lowest rates and those in therapeutic communities described intermediate rates. A series of regression analyses showed that the only significant predictors of the frequency of heavier drinking and drunkenness were drinking context and reasons for combining alcohol and drug use. In addition, age (youthfulness) was associated with the frequency of getting drunk. The most powerful predictors of alcohol-related problems were the frequency of getting drunk and drinking to enhance the effects of other drugs. Heavy drinking and drinking to prevent getting sick from drugs were also significantly associated with drinking problems. The frequency of drug use (by specific type) and most social characteristics showed no direct association with drinking patterns or problems. PMID- 8486083 TI - Social support and anxiety in pregnant drug abusers and nonusers: unexpected findings of few differences. AB - Drug-abusing (n = 25) and nonusing (n = 55) pregnant women from a publicly supported prenatal clinic were tested for level of social support and of pregnancy anxiety during the last half of pregnancy. Differences found between the groups were fewer than expected. Drug abusers did not differ from nonusers in overall level of social support or in Appraisal, Belonging, or Tangible subscales. Abusers were found to report lower levels of self esteem; lower self esteem was predicted by drug abuse, having more children and lower socioeconomic status. Drug abusers did not differ from nonusers in their overall feelings of pregnancy anxiety, but they did indicate higher fears for themselves and for the baby, and there was a tendency for higher depression and withdrawal. PMID- 8486084 TI - Assessing the behavioral effects and abuse potential of propofol bolus injections in healthy volunteers. AB - Propofol is a recently introduced intravenous anesthetic agent, commonly administered to surgical patients because it induces anesthesia smoothly (i.e., provides loss of consciousness rapidly and usually with no complications) and is associated with rapid recovery. Propofol has psychoactive effects that could be construed as pleasant, although little abuse liability testing has been done on this agent in humans. Accordingly, we examined various effects of this agent at different subanesthetic doses (0.2-0.6 mg/kg) in order to characterize this drug's abuse potential (for recreational use or potential for diversion). Using a double-blind, randomized, crossover design, healthy normal volunteers (N = 10) were injected intravenously with the drug or with placebo. Before the injection and for up to 1 h afterwards, mood (including drug liking), memory and psychomotor performance were assessed. Propofol impaired memory and psychomotor performance and produced changes in 10 of 20 VAS mood ratings. Although there was variability in self-reported drug liking, some subjects clearly liked the effects of propofol, especially at the two higher doses. At the debriefing interview held after completion of the study, five subjects said if they had to participate in one more session in which they were given a choice between being injected with the highest dose (0.6 mg/kg) or a placebo, they would choose propofol. These preliminary results suggest that this agent may have some potential for abuse/diversion and perhaps stricter accountability procedures should be established for this drug in settings where general anesthesia or conscious sedation procedures are done. PMID- 8486085 TI - Induction of antibodies to morphine during chronic morphine treatment in rodents and opiate addicts. AB - The phenomenon of induction of antibodies to morphine in morphine-treated animals and opiate addicts was shown by means of ELISA. The reaction of the immune system to injections of a morphine solution had the characteristics of a primary immune response. Opiate addicts differed from normal controls in the level of antibodies to morphine of IgM class. Elevated levels of such antibodies could be detected in about 70-80% of addicts with regular longterm opiate use when the time since the last drug intake did not exceed 60 days. Antibodies to morphine could serve as indicators of chronic opiate use especially in periods long after the last drug intake. PMID- 8486086 TI - GBR 12909 fails to antagonize cocaine-induced elevation of dopamine in striatal slices. AB - The effects of cocaine and 1-(2-bis (4-fluorophenyl)methoxy)-ethyl)-4-(3-phenyl propyl) piperazine (GBR 12909), alone and together, on [3H] dopamine efflux from superfused rat striatal slices was studied. Both drugs elicited a concentration dependent increase in spontaneous [3H]dopamine efflux. GBR 12909 when added together with cocaine, had no effect on cocaine-induced [3H] dopamine efflux. It was also determined that GBR 12909 was fully efficacious as an inhibitor of synaptosomal [3H] dopamine uptake and, whether administered in vitro or in vivo, acted in a manner consistent with competitive inhibition. These data are discussed in reference to the recent report that i.p. administration of GBR 12909 antagonized the effect of cocaine on extracellular striatal dopamine levels when infused directly through the dialysis probe, perhaps by acting as a 'partial agonist' at the inhibitory site on the dopamine transporter (Rothman et al., 1991 Pharmacol. Biochem. Behav. 40, 387-397). PMID- 8486087 TI - Prison experience of injecting drug users in Glasgow. AB - Five hundred three injecting drug users in Glasgow recruited by a multisite and citywide sampling strategy were questioned regarding their drug-taking behaviour during episodes of custody over the six months prior to interview. Fifty-two percent had been in custody during the past 6 months, 16% of these had injected while in custody. Of these 73% borrowed injecting equipment and 78% handed on used equipment to others. All those who shared, cleaned their injecting sets before use. Over half of those who injected had a source of new sets. While the potential exists for spread of HIV among drug users while in custody there is clear understanding among them of the route by which the virus is spread and also the will to prevent it. PMID- 8486088 TI - [Infusion therapy in newborn calves with diarrhea from the area of Ankara with special reference to acidosis (part 1)]. AB - Characteristic changes (hyperkalemia, metabolic acidosis and azotemia) occurred in the blood of 54 calves 1 to 15 days old with diarrhoea. Clinical signs of dehydration were observed. Average values were: Potassium 6.37 mmol/l, pH 7.17, bicarbonate 18.76 mmol/l, base excess (BE)-10.01 mmol/l, urea % 78.2 mg. The amount of 1.3% sodium bicarbonate solution to be given to calves with patent metabolic acidosis was determined according to the following formula: HCO3- (mmol/l = body weight (kg) x 0.5 x BE. In most of the cases with severe metabolic acidosis (pH < 7.0), a good compensating effect was obtained. Infusion treatment brought blood pH and base excess values near to normal, and bicarbonate concentration to within the physiological range. Balanced solutions were used in the regulation of electrolyte-fluid balance. Hematocrit, potassium and urea values, which had been pathologically high, returned to normal following infusion treatment. Apart from this, patients were given symptomatic treatment according to the important clinical findings. Forty-two animals recovered completely after intravenous infusion of buffer and electrolyte solutions. Twelve out the total of 54 animals died within 1-5 days despite infusion treatment. PMID- 8486089 TI - Studies on the teratogenic effects of deltamethrin in rats. AB - Deltamethrin is a pyrethroid insecticide used to eradicate external parasites on farm animals. Residues of this pesticide were shown to be present in food from animal origin which encouraged us to investigate the effects of deltamethrin on foetuses of pregnant rats. Literature search shows that previous research was focused on organochlorine and organophosphate pesticides whereas little attention was given to the newer pyrethroid insecticides. Four groups of pregnant rats (20 rats each) were given either the vehicle (control) or doses of 1, 2.5 or 5 mg/kg b. w. of deltamethrin orally from day 6 to day 15 of pregnancy which was terminated by killing the animals on the 19th day for foetal examinations. The incidence of early embryonic deaths was higher in deltamethrin-treated rats than in control females. Deltamethrin caused retardation of growth, hypoplasia of the lungs, dilatation of the renal pelvis and increase in placental weight. No skeletal changes were observed in foetuses recovered from deltamethrin-treated females. Although deltamethrin is relatively safe, however its effects on the foetus should be considered when used on pregnant animals or in environments where pregnant animals and women live. PMID- 8486090 TI - [The reproductive performance of sows with different malignant hyperthermia syndrome status]. AB - Based on 200 litters descending from 50 sows relations between MHS-genotype and reproductivity were investigated. Breeds used were "Deutsches Edelschwein", German Landrace and a crossbred line. Evaluation of MHS-status was done by Polymerase Chain Reaction. Reproductivity traits were piglet numbers at different ages and litter growth. The sows were not preselected in regard to the halothane gene. MHS-negative sows showed increased reproductivity towards MHS-positives and within the negatives, the homozygote sows were superior to the heterozygotes. PMID- 8486091 TI - Prophylactic application of Propionibacterium avidum KP-40 in swine with acute experimental infections. I. Viral infections--Aujeszky's disease and classical swine fever. AB - The usefulness of the prophylactic application of Propionibacterium avidum KP-40 (PA), a potent stimulator of the macrophage-monocyte system and inducer of endogenous interferons, was demonstrated in swine infected experimentally with Aujeszky's disease or classical swine fever viruses. Some of the infected animals were preimmunized with respective vaccines containing live, attenuated viruses. In vaccinated and non-vaccinated swine infected with Aujeszky's disease virus, pretreatment with PA lowered the morbidity rate, shortened the period of fever and fastened the recovery. Infection with classical swine fever virus resulted in 100% mortality of PA-pretreated non-vaccinated swine, but the length survival of the animals was significantly longer (p < 0.05). PMID- 8486092 TI - [Pharmacokinetics of sulfamerazine after a single intravenous dose in healthy calves and calves with diarrhea of different severity with consideration of the influence of an existing kidney function restriction]. AB - Blood levels of Sulfamerazine were examined in 16 calves with different severity of diarrhoea in consideration of kidney function and compared with the values of 5 clinically intact animals. Urea and creatinine levels in plasma as well as urea and creatine clearance were tested to check kidney function. A single dose of 60 mg Sulfamerazine/kg body weight was administered to all animals via catheter into the vena jugularis. Blood samples were collected for 48 hours. The mean concentration of Sulfamerazine in calves with severe diarrhoea was significantly higher 24 hours post application than in the healthy control group and in animals with low and middle intensive diarrhoea (healthy animals: 37.61 +/- 7.18 micrograms/ml; animals with severe diarrhoea: 57.3 +/- 7.5 micrograms/ml). Animals with severe diarrhoea showed significantly higher values of half life time of elimination t1/2 (healthy animals: 7.08 +/- 1.25 h; animals with severe diarrhoea: 11.39 +/- 2.11 h) and of area under the curve AUC (healthy animals: 2023.4 +/- 397.21 micrograms*h/ml; animals with severe diarrhoea: 2990.6 +/- 594.9 micrograms*h/ml) than the others. Low and middle intensive diarrhoea has no important influence on the pharmacokinetics of Sulfamerazine. PMID- 8486093 TI - [Hunting and animal protection]. AB - In the Federal Republic of Germany the handling of animals during hunting is governed more by the animal protection law than by the corresponding hunting law. Points of the animal protection law which directly affect hunting are (1) the release of wild animals, (2) the training and examination of animals concerning attacking other animals, (3) the setting of animals on other animals, and (4) the killing of vertebrates. Guiding principles for killing wild animals during hunting according to the animal protection law are formulated and discussed in relation to the traditional German understanding of hunting ethics. It can be expected that hunting will increasingly become a topic of public discussion on animal protection, in which the ethics of hunting in relation to the wild animal will be dominant. PMID- 8486094 TI - [Ultrasound studies for the demarcation of the spatial extension of teat stenosis and other teat changes in cattle]. AB - Under field conditions in 63 dairy cows a stenosis of the teat was diagnosed in 60 cases and other teat anomalies were found in 5 animals. The results of a traditional clinical examination were compared with results obtained by diagnostic with a portable, 5 MHz linear scanner. The pictures found in unaltered teats were compared with pathological findings. As far as the localisation and extension of teat stenoses or lacerations of the mucosa in the teat is concerned, the accuracy of the diagnosis was improved by ultrasonography. Diagnostic ultrasound can be recommended as an additional diagnostic tool in certain cases of a stenosis or other anomalies of the teat in dairy cows. PMID- 8486095 TI - Effect of indomethacin, aspirin, nordihydroguairetic acid, and piperonyl butoxide on cyclophosphamide-induced bladder damage. AB - Cyclophosphamide (CP), a widely used antineoplastic and immunosuppressant drug, is a prototypical bladder toxin in humans and experimental animals. CP itself is biologically inert. However, following bioactivation, acrolein, a potent tissue alkylator is generated. It is currently accepted that CP activation occurs via oxidative metabolism by the mixed-function oxidase system (MFO). Previous evidence from this laboratory demonstrated that CP can be metabolized by pathways other than MFO. In the current study, it was demonstrated that two inhibitors of the prostaglandin hydroperoxide synthase enzyme system, indomethacin and nordihydroguairetic acid (NDGA), diminish CP-induced bladder toxicity. However, the ability of these inhibitors to provide protection did not appear to be due to interference with CP metabolism. Many of the biologic effects of acrolein have been attributed to interaction with cellular thiols. Indomethacin and NDGA protected against CP-induced losses of soluble thiols in liver and protein thiols in bladder. Additionally, animals pretreated with indomethacin prior to CP appeared to have more glutathione available for conjugation, providing a potential mechanism for its protective effects against CP-induced bladder damage. PMID- 8486096 TI - Characterization of protein phosphorylation by 2,3,7,8-tetrachlorodibenzo-p dioxin in murine lymphocytes: indirect evidence for a role in the suppression of humoral immunity. AB - Studies were undertaken to more thoroughly characterize 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-induced stimulation of kinase activity in murine lymphocytes. In female B6C3F1 mice, TCDD-induced phosphorylation of 29, 45, 52 and 63 KDa proteins was selective for B cells, with little or no enhancement observed in T cells. When B cells were purified and separated by density on a percoll gradient, phosphorylation was only observed in the band composed of activated B cells, and was not enhanced in the band composed of resting B cells. TCDD-stimulated phosphorylation was associated with both the cytosol (45 and 52 KDa species) and membrane (52 KDa species) fractions. Purified B cells from both DBA/2 (Ahdd) and C57B16 (Ahbb) mice demonstrated equivalent enhancement of phosphorylation in response to TCDD. Administration of human gamma interferon (Hu-IFNg) at concentrations from 0.5 to 500 Units/ml produced a dose related reversal of TCDD-induced suppression of in vitro antibody responses to both the polyclonal B cell activator, LPS, and the T-dependent antigen, sRBC in whole splenocytes isolated from female B6C3F1 mice. These concentrations of Hu IFNg did not affect the magnitude of either response in the absence of TCDD, and did not reverse dexamethasone-induced suppression of either in vitro antibody response. TCDD-induced suppression of the T-dependent response was reversed only when Hu-IFNg was added to culture within the first 18 hours after treatment with TCDD and sRBC. These studies demonstrate that Hu-IFNg can reverse TCDD-induced in vitro Ab response suppression if it is administered during the period of susceptibility to TCDD. TCDD-induced phosphorylation in isolated B cells was also antagonized following co-incubation with Hu-IFNg. The profile of TCDD-induced increases in protein phosphorylation, including the selective effect on activated B cells, the general involvement of both cytosolic and membrane proteins, the lack of segregation with the Ah-dependent processes, and the ability of Hu-IFNg to reverse both the suppression of the Ab response and the increase in phosphorylation, supports the interpretation that such phosphorylation is involved in TCDD-induced suppression of the Ab response. PMID- 8486097 TI - Effect of cyclosporin A and its metabolites and analogs on lipid peroxidation in rabbit renal microsomes. AB - Rabbit renal microsomes were used to investigate the effect on lipid peroxidation (LPO) of cyclosporin A (CsA) and its first generation metabolites M1, M17 and M21, and of two natural CsA analogs: cyclosporins C and D (CsC & CsD respectively), at concentrations of 1 to 10 micrograms/ml. No induction of lipid peroxidation was observed with these substances except CsA at a high level (10 microgram/ml); but at a concentration of CsA that would be reached in vivo, no inductive effect on LPO was noted. A moderate inhibitory effect upon LPO was observed with CsC and M21, but its biological significance is questionable. PMID- 8486098 TI - Inhalation studies in rats exposed to dimethylacetamide (DMAc) from 3 to 12 hours per day. AB - Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentrations were increased in rats exposed for 12 hours/day to either 30, 100, or 300 ppm. Hepatocellular hypertrophy together with margination of hepatocellular cytoplasmic contents and lipid-like cytoplasmic vacuolation in hepatocytes were seen microscopically only in rats exposed for 12 hours/day to 300 ppm. Recovery from these liver changes was not complete after 14-day post-exposure period. No evidence of either testicular damage or irritation to the upper respiratory tract was seen. PMID- 8486099 TI - Buflomedil: one-year oral safety evaluation in rats. AB - Buflomedil was given as a dietary mix to Sprague-Dawley Rats for one year at dosages of 0, 25, 75, and 400 mg/kg/day. Each group contained thirty rats of each sex, of which 10/sex/group were preassigned to a withdrawal period of 3 months following the 1-year drug administration period. There were no treatment-related deaths or clinical signs. Dosage-related decreases in body weight gain occurred during the 1-year treatment period. Food consumption was comparable to controls, except for a 10% decrease in high-dosage males during the first week of treatment. During the withdrawal period, body weight gain was higher than controls in all drug-treated groups. Hematocrit (PCV) and hemoglobin were slightly decreased during week 52 in high-dosage males; hematology values were comparable to controls during weeks 13 and 26 and at the end of the withdrawal period. There were no treatment-related changes in blood biochemistry. Urine pH was decreased in females at 75 mg/kg/day and in both sexes at 400 mg/kg/day. Discolored urine was observed in males at 75 mg/kg/day and in both sexes at 400 mg/kg/day. Urine pH and color were comparable to controls after the 3-month withdrawal period. There were slight decreases compared to controls in urine volume at all dosages in females during week 52; these changes were still evident in the mid- and high-dosage groups at the end of the withdrawal period. The only possibly treatment-related observation at necropsy was dirty tails at the end of the treatment period in the high-dosage group which may have been related to the discolored urine. Liver and kidney weights were slightly increased in males at 400 mg/kg/day at the end of the 1-year treatment period; these changes were not evident after the 3-month withdrawal period. There were no treatment-related histopathological changes. The changes observed were thought to result from either pharmacologic activity or physiological adaptation to compound administration or were marginal in severity. None were considered toxicologically significant. Therefore, the no-toxic-effect dosage was 400 mg/kg/day which is 40 times the maximum clinical dosage. PMID- 8486100 TI - Captan metabolism in humans yields two biomarkers, tetrahydrophthalimide (THPI) and thiazolidine-2-thione-4-carboxylic acid (TTCA) in urine. AB - Captan fungicide (N-(trichloromethylthio)-4-cyclohexene-1,2-dicarboximide) metabolism in two human volunteers rapidly yields THPI (tetrahydrophthalimide) and TTCA (thiazolidine-2-thione-4-carboxylic acid). The work was done to evaluate usefulness of TTCA and THPI as biomarkers of occupational exposure and to compare human and rat dermal absorption and metabolism. THPI in 12h urine ranged from MDL (5 ppb) to 640 ppb and was stable for at least one year. TTCA was also a stable metabolite, but the MDL was 50 ppb. THPI was detectable in urine for 72 hours following oral dosages of 1 mg/kg, but most was eliminated 0-24 h. No THPI was detectable in urine following application of a chloroform solution to hands, forearms, or inguinal region. Dermal absorption and metabolism of captan are substantially different in humans and rats. PMID- 8486101 TI - Consequences of vocal cord hemorrhage. PMID- 8486102 TI - Secretory otitis media (glue ear). PMID- 8486103 TI - Endoscopic anatomy of the nasal cavity. PMID- 8486104 TI - Pediatric sinusitis and surgery revisited. PMID- 8486105 TI - Warthin's tumor-associated neoplasms: report of two cases and review of the literature. AB - The association of Warthin's tumor with another neoplasm of a different histological type in the same salivary gland is extremely rare. The literature includes 42 such cases to date. A case of malignant lymphoma developing within Warthin's tumor and another case of oncocytoma synchronous with Warthin's tumor in the same parotid gland are reported. The relation of Warthin's tumor to other neoplasms is discussed. PMID- 8486106 TI - Ewing's sarcoma of the nose. AB - Ewing's sarcoma is a bone tumor that rarely arises in the head and neck region. Head and neck tumors account for only 2% to 3% of all Ewing's sarcomas. There is an extremely rare subgroup of Ewing's tumors, that are histologically indistinguishable, which are not metastatic and arise in soft tissue rather than bone. Two Ewing's sarcomas of the nose are described. One case is the first reported nasal Ewing's soft tissue sarcoma. The other case is the more traditional type involving bone of the nose and extending into ethmoid sinuses and intracranially. PMID- 8486107 TI - Myxomas of the mandible and maxilla. AB - Myxomas of the mandible and maxillary sinus are rare but well described neoplasms. They appear to be odontogenic in origin related to malformations or missing teeth. Their local aggressiveness and ability to erode bone should not be underestimated. Based on our experience we feel that conservative surgical management including total excision and sparing of uninvolved structures allows for preservation of function. Long-term follow-up is necessary and in case of recurrence, a more radical procedure may have to be performed for this benign disease. PMID- 8486108 TI - Malignant melanoma of the nasal cavity and paranasal sinuses. PMID- 8486109 TI - Sinus histiocytosis--a rare tumor involving the paranasal sinuses. PMID- 8486110 TI - Adult rhabdomyoma of the larynx. AB - Rhabdomyomas of the larynx are rare lesions, with the "adult" type occurring more frequently than the "fetal" type. Treatment is complete surgical removal. Recurrences would suggest an incomplete surgical procedure and/or an incorrect pathological diagnosis. PMID- 8486111 TI - Intramuscular hemangiomas of the masseter and sternomastoid muscles. AB - Two cases of hemangiomas involving the masseter and sternomastoid muscle are added to the English literature. Our limited experience with these cases confirms that preoperative diagnosis and planning can be difficult. Recurrences of tumors are related to incomplete excisions although their further treatments in the final analysis depend on the adjacent structures affected. Careful individualization of treatment is therefore a necessity. Embolization is not sufficient therapy if not followed by surgery. PMID- 8486112 TI - Pediatric sinusitis is not a surgical disease. PMID- 8486113 TI - Spontaneous recovery after severe metabolic acidaemia at birth. AB - Twenty-two severely acidaemic babies (mean umbilical artery pH 7.00), born at term but not requiring resuscitation, were matched for gestational age, mode of delivery and birthweight with non-acidaemic infants. Skin-puncture pH, PCO2 and base deficit were measured at 1 h of age in the acidaemic group. Mean respiratory and heart rates at 30 and 60 min in the two groups were not significantly different. The improvement in pH and base deficit in the acidaemic group correlated with PCO2 at 1 h of age but not with respiratory rates, heart rates or birthweight. However, all four small-for-gestational age infants and one other showed a significantly smaller rise in pH (mean 0.09) compared with the others (mean 0.33). This was associated with a smaller fall in PCO2 and no change in base deficit and these babies were not identified by clinical observations at 1 h of age. Thus, clinical observations of respiratory and heart rates over the first hour of life did not distinguish babies born with severe metabolic acidaemia and did not identify babies who were less efficient at compensating for the acidaemia. PMID- 8486114 TI - Relative contribution of physical activity to neonatal oxygen consumption. AB - To explore the relevance of distinguishing between resting and global energy expenditure in newborn infants, oxygen consumption (VO2) was measured during extremes of physical activity in 17 parenterally fed newborn infants with a large range of body weights (1.0-3.4 kg) and gestational ages (28-41 weeks). Under constant nutrient intakes, each infant served as his/her own control when comparing VO2 during resting conditions and spontaneous intense physical activity, called exercise. VO2 was significantly correlated with body weight at rest (r = 0.96). But during intense activity, the better predictor of exercise induced VO2 was body weight in the smaller infants (< 2.0 kg) and gestational age in the larger infants (> 35 weeks). The difference in VO2 between both levels of activity represented the oxygen cost of exercise, which decreased (P < 0.01) with body weight. For clinical purposes, the physical activity of low-birth-weight infants does not contribute substantially to their energy balance. PMID- 8486115 TI - The effect of moderate maternal alcohol consumption on birth weight and gestational age in a low risk population. AB - We analyzed the relationship between moderate maternal alcohol consumption during pregnancy and both birth weight corrected for gestational age and preterm delivery in 3447 women. Information on alcohol consumption in the first and second trimester was obtained during mid pregnancy and information about third trimester drinking was obtained a few days after delivery. After adjustment for possible confounders we found that for most women alcohol consumption was unrelated to birth weight corrected for gestational age and preterm delivery. However, in the subgroup of women smoking 20 cigarettes or more a day, drinking more than 120 g alcohol a week in early pregnancy was associated with a 7.2% (95% CI 0.2% to 14.2%) decrease in birth weight. We conclude that the effect of alcohol use on birth weight corrected for gestational age and gestational age is limited. However, in women who smoke heavily, a reported consumption of about two drinks or more a day in early pregnancy may be an additional risk factor for impaired fetal growth. PMID- 8486116 TI - Cellular composition of the telencephalic wall in human embryos. AB - Cellular composition and lamination of the telencephalic wall (TW) was studied with Golgi impregnation in human embryos before and during the cortical plate formation (5, 6-7 and 7-8 gestational weeks (g.w.)). During this period, the telencephalic wall increased in width and lamination pattern became complex while cellular morphology reflected progressive differentiation. At 5 g.w. (Carnegie stage 16) TW was 140 microns wide and had two zones, marginal (MZ) and ventricular (VZ). It was built exclusively of bipolar ventricular cells and their upward directed processes. One week later, at 6 g.w. (stages 17 and 18) the telencephalic wall displayed three zones (VZ, intermediate-IZ, MZ) and increased to 220 microns. Sparse detached cells were found in the VZ while more of these cells were observed above VZ, in the incipient intermediate zone. These neurons were either simple or branched bipolar, and mainly oriented vertically in respect to the outer surface. However, horizontally oriented cells were also noticed either at the VZ/IZ border or immediately below the pia, where they probably represented Cajal-Retzius neurons. At 7-8 g.w. (stages 20-22), the cortical plate appeared between the IZ and the MZ at the ventrolateral level of the telencephalic wall. Intermediate zone could be further divided into a more superficial part or a presubplate layer (IZ1) and a deep part or a future white matter (IZ2). Thus, at this stage, TW consisted of five zones (VZ, subventricular, IZ with the presubplate, cortical plate-CP and MZ). The width of TW increased to 370-400 microns. Cortical plate cells were fusiform, with the apical dendrite branching into the MZ, and the axon directed in the opposite direction. Below it, differentiated neurons of the presubplate displayed a variety of morphological forms. The presence of horizontally oriented cells on the border of ventricular and subventricular zone was noteworthy. Impregnated bundles of horizontal fibres were encountered in the IZ and MZ of the telencephalic wall at 6 g.w. Their number increased in 7- to 8-g.w. embryos, especially in the lower (future white matter) and upper (future subplate) intermediate zone. Our results on the cellular development of the cortical anlage, as revealed by Golgi method, not only support results obtained on different experimental animals but also add new relevant evidence about human development. Data on transition of simple bipolar ventricular cells to different neuronal shapes as constituents of emerging new laminae were not available for human cortical anlage. PMID- 8486117 TI - The predictive value of Doppler flow velocity waveforms in the development of abnormal fetal heart rate traces in intrauterine growth retardation: a longitudinal study. AB - In a longitudinal, blinded study design the predictive value of Doppler velocimetry for the development of an abnormal fetal heart rate trace was assessed in 42 cases of intrauterine growth retardation. Doppler velocity waveform recordings were obtained at 2- to 3-day intervals and characterized by the standard deviation score of the pulsatility index in the umbilical artery and internal carotid artery, and the peak systolic and time-averaged velocity in the ascending aorta and pulmonary artery. Twenty-seven patients did not display an abnormal fetal heart rate trace on the day of entry into the study. During follow up of these patients, the pulsatility index in the umbilical artery and internal carotid artery were the most predictive parameters for the development of an abnormal fetal heart rate trace. The resulting prognostic index was found to have an acceptable discriminative power in the prediction of abnormal fetal heart rate traces as established in a second group of growth-retarded fetuses. PMID- 8486118 TI - The effect of intra-uterine breech position on postnatal motor functions of the lower limbs. AB - The effect of intra-uterine movement restriction on the development of motor functions was studied longitudinally by comparing infants born after uncomplicated breech position (n = 13) with control infants (vertex position, n = 5-10). Before birth, fetal leg posture was studied at regular intervals by means of real time ultrasound observations, and classified as complete (n = 1), inconsistent (n = 6), or incomplete (n = 6) breech position. Limited extension of the hips, preference posture and joint position in percentage of time (each until 12 weeks), withdrawal reflex and magnet response (until 26 weeks) and posture while sitting, standing and walking without support (up to 12-18 months) were assessed longitudinally. The results showed statistically significant, positive relationships between intra-uterine breech position and neonatal limited extension of the hip-joint, between limited extension of the hip-joint and the percentage of time that the hips are in flexion during the first 12 weeks, between this flexion of the hips (in percentage of time) and an abnormally 'flexed' walking pattern at 12-18 months, and finally, between a positive magnet response at 6 months and an abnormal walking pattern at 12-18 months. These findings suggest that intra-uterine movement restriction of the legs can cause long term alterations in the development of motor functions (leg posture, reflexes and posture while walking), possibly mediated by alterations in proprioceptive feedback mechanisms. PMID- 8486119 TI - The intercostal-to-phrenic-inhibitory reflex (IPIR) in normal and intra-uterine growth-retarded (IUGR) human fetuses from 26 to 40 weeks of gestation. AB - The existence of an IPIR in the healthy fetus between 37 and 40 weeks of gestation has already been demonstrated: compression of the fetal thoracic wall during an epoch of fetal breathing movements (FBM) consistently caused a fetal apnea (> or = 4 s). The apnea durations were similar in fetal behavioural states 1F and 2F, with a wide inter- and intrafetal variability. We therefore hypothesized that the duration of the IPIR-apnea would increase during gestation and would be increased in IUGR-fetuses as compared to healthy fetuses of the same age. Twenty-six healthy fetuses between 28 and 40 weeks (mean 34.3 weeks) and 14 IUGR-fetuses between 26 and 38 weeks (mean 33.5 weeks) were studied. If FBM were present, the caudolateral part of the fetal thoracic wall was shortly compressed manually and the duration of the resulting apnea was measured. In a random order a sham-compression was also carried out on the fetal head. In normal fetuses 21/28 real compressions were followed by an apnea in 1F, while this was only the case in 3/21 sham-compressions (P < 10(-4)). For 2F these results were 47/57 and 7/51, respectively (P < 10(-4)). In IUGR-fetuses 43/51 real compressions (1F and 2F together) and 7/46 sham-procedures provoked an apnea (P < 10(-4)). These results prove the existence of the IPIR in normal and IUGR-fetuses. The mean (+/- S.D.) duration of apnea in the IUGR-fetuses was 15.8 s (+/- 4.0) (range 4-80 s) and 15.2 s (+/- 4.3) (range 4-106 s) in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486120 TI - Heart-rate variability in low-risk prematurely born infants reaching normal term: a comparison with full-term newborns. AB - To investigate the influence of prematurity and postnatal age on the maturation of the autonomic nervous system function, we analysed heart-rate and heart-rate variability in twelve prematurely born infants (< 37 weeks gestational age) reaching the conceptional age of 37-41 weeks. These neonates were compared with sixteen 37-41 week conceptional age newborns (< 10 days postnatal age). Heart rate variability was analysed by spectral analysis of interbeat intervals using Short-Time Fourier Transform. We found that during both active and quiet sleep, the durations of RR-intervals were shorter and the amplitude of heart-rate variability in different frequency bands was lower in prematures reaching term than in newborns of the same conceptional age (P < 0.001). Between-state comparison showed differences in both groups. In both groups, low-frequency heart rate variability was higher in active sleep than in quiet sleep. Between-state differences of RR-intervals and high-frequency heart-rate variability were present only in newborns (P < 0.01). Discrimination between newborns and prematures reaching term, based on RR-intervals and heart-rate variability, was correct in both sleep states with errors between 7 to 16%. However, in both newborns and prematures reaching term, between-state discrimination showed less reliable results, especially for quiet sleep discrimination with 24% (in PRT) and 20% (in NB) of errors. Our results, especially information given by factor analysis, suggest that the differences between newborns and prematures reaching term, concerning RR-interval and heart-rate variability, may be related to a changed balance between the sympathetic and parasympathetic nervous systems with a diminished parasympathetic component of heart rate control in prematures reaching term, as compared to newborns. PMID- 8486121 TI - The incidence of obstructive apneas in preterm infants with and without bronchopulmonary dysplasia. AB - We tested the hypotheses that (1) preterm infants with bronchopulmonary dysplasia (BPD) have an increased incidence of obstructive apneas as compared to those without BPD (control) and (2) the respiratory pattern during obstructive apneas may be associated with more pronounced hypoventilation. Ventilation was measured with a flow-through system. We examined 2929 total apneas in 12 infants with BPD and 4366 apneas in 12 control infants matched for study weight (1.51 +/- 0.11 kg in the BPD group and 1.62 +/- 0.12 kg in the control group, P = 0.6) and for postconceptional age (33.3 +/- 0.8 weeks in the BPD group compared with 33.4 +/- 0.7 weeks in the control group, P = 0.6). The incidence of central apneas predominated in the BPD group (2551/2929, 87%) and in the control group (4188/4366, 96%). Obstructive apneas were more frequent in the BPD group (378/2929, 13%) than in the control group (178/4366, 4%, P = 0.004). The increased incidence of obstructive apneas in infants with BPD was observed in Quiet sleep (9.1 vs. 1.6%, P = 0.03) and in REM sleep (14.2 vs. 3.6%, P = 0.009). This increased incidence of obstructive apneas was applicable to short apneas (< 10 s, 10.9 vs. 2.7%, P = 0.003) and long apneas (> 10 s, 27.5 vs. 16.4%, P = 0.01). There were no significant changes in ventilatory pattern that could be uniquely attributed to one type of apnea. The findings suggest: (1) the great variability in the incidence of obstructive apneas reported in the literature relates, at least in part, to the clinical status of the infants and (2) ventilatory pattern is not a useful predictor of either type of apnea. PMID- 8486122 TI - Indicators of long chain polyunsaturated fatty acid status of exclusively breastfed infants at delivery and after 20-22 days. AB - The fatty acid composition of plasma cholesterol esters (CE), erythrocytes (RBC) and mature milk from seven lactating/women and their exclusively breastfed newborns, living on Dominica, were studied. Blood samples were taken from umbilical cord and mother at birth. A sample of breastmilk was collected on day 20-22 postpartum, together with a blood sample from the baby. At birth, cord blood plasma CE and RBC total long chain polyunsaturated fatty acid (LC-PUFA) contents were higher, and linoleic (18:2c, omega 6) and alpha-linolenic (18:3c, omega 3) acid contents lower, than in corresponding maternal compartments. Cord blood RBC LC-PUFA omega 3 content was lower and LC-PUFA omega 6 content higher than in maternal RBC. After birth, feeding with human milk led to a drop in LC PUFA content in the plasma CE fraction, whereas RBC LC-PUFA content remained virtually constant. Current understanding of the origin and relative affinity of fatty acids incorporated in plasma CE and RBC suggests that RBC LC-PUFA content is a more reliable parameter for LC-PUFA status than plasma CE LC-PUFA content. The RBC LC-PUFA data suggest therefore that at birth the newborn has a lower LC PUFA omega 3 status than the mother, and that this does not change during three weeks of exclusive breastfeeding. PMID- 8486123 TI - Fetal C-reactive protein. AB - C-reactive protein (CRP) was measured in fetal blood obtained by cordocentesis from 17 patients with preterm prelabour rupture of the membranes (PPROM). CRP was detected in the blood of eight of the 17 fetuses. Six fetuses, five of whom may have been infected had CRP > or = 0.8 mg dl-1. The remaining 11 fetuses as well as 25 healthy term infants who had cord blood taken immediately post delivery had CRP < 0.6 mg dl-1. These results suggest that elevation of fetal CRP levels may be a useful indicator of fetal infection in pregnancies complicated by PPROM. PMID- 8486124 TI - Respiratory status and diuresis following treatment with dexamethasone. AB - The effect of dexamethasone therapy on fluid balance, lung function and requirement for respiratory support has been assessed. Ten premature infants were studied, they had a median gestational age of 28 weeks. None of the infants had any improvement in the respiratory status for 48 h prior to commencing dexamethasone. Fluid balance, pulmonary function and requirement for respiratory support were measured 12 h prior to and for 36 h after receiving dexamethasone. There were no significant changes in fluid input over the study period, but urine output increased significantly after 12 h of dexamethasone therapy (P < 0.02). Compliance of the respiratory system only significantly improved after 36 h of dexamethasone therapy (P < 0.03), this was associated with a significant change in the inspired oxygen concentration (P < 0.05). We conclude that the improvement in respiratory status resulting from dexamethasone therapy is preceded by a diuresis. PMID- 8486125 TI - Morphometric development of the human auditory system: ventral cochlear nucleus. AB - The development of the human cochlear nucleus was studied in serial sections of the brain of 12 fetuses at 12-40 weeks of gestation, an infant at 2 months of age and an adult of 63 years using an electronic planimeter with a computer. Morphometric analysis of the development of the ventral cochlear nucleus showed that its development accelerates after 18 weeks of gestation in terms of columnar volume, columnar length, neuronal number and neuronal size. PMID- 8486126 TI - Typing of the 3' hypervariable region of the apolipoprotein B gene: approaches, pitfalls, and applications. AB - Apolipoprotein B-100 is the principal protein component of lipoproteins with very low, intermediate, and low density. The interaction of apoB-100 with low density lipoprotein (LDL) receptors is responsible for the uptake of LDL into cells. An AT-rich hypervariable region is located adjacent to the 3' end of the apoB gene. It consists of a variable number of tandemly repeated sequences (VNTR). Two approaches were used to analyze this polymorphism. In both, the region harboring the VNTR was amplified with the polymerase chain reaction (PCR). In the first method, fluorescently labeled primers were used in the PCR reactions and products were separated in agarose gels by means of an automated fluorescent fragment analyzer. In the second method, PCR products were analyzed in denaturing polyacrylamide gels and detected with silver staining. Even in the highly sophisticated automated system, agarose gel electrophoresis did not always enable unequivocal assignment of VNTR alleles. In contrast, denaturing polyacrylamide gel electrophoresis made it possible to distinguish the 15 bp differences between the VNTR alleles in a precise and simple manner. The VNTR polymorphism was typed in 234 individuals. Among these were 136 patients with coronary artery disease and 74 healthy controls. Thirteen alleles could be distinguished. The allele containing 49 repeats (VNTR-49) was found in 9.2% of the coronary artery disease patients and in 4.7% of the controls. Thus, the VNTR-49 allele increases relative coronary risk by about twofold. It is concluded that the apoB VNTR polymorphism is a potentially useful genetic marker. Since agarose gel electrophoresis may lead to ambiguous results, we prefer typing by denaturing polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486127 TI - Amplification of a Y-chromosomal DNA sequence by the polymerase chain reaction for documentation of residual recipient cells in small samples from bone marrow, peripheral blood and cerebrospinal fluid after bone marrow transplantation. AB - The long arm of the human Y-chromosome contains about 800 to 5000 copies of the tandemly repeated DNA sequence DYZ1. A major part of the repeating unit (pHY10) has been cloned and sequenced. Primers were designed to match a part of this repeat sequence for the amplification of a 154 bp fragment spanning the EcoRI restriction site of the unit. Typical dilution experiments showed that this polymerase chain reaction (PCR) method allows the detection of 5 to 10 male cells among 100,000 female cells, or in 500 microL of cerebrospinal fluid containing only one cell per microL. In addition, the quality of the DNA used for the amplification reaction is less critical, thus allowing analysis of long-term stored samples such as bone marrow smears or dried blood stains spotted onto filter paper, which might contain partially degraded DNA. We applied this technique to detect residual host cells in the clinical setting of human sex mismatched bone marrow transplantation (BMT). Fourteen patients, receiving transplantations because of leukemias could be supervised so far. Throughout the whole period of monitoring (days +14 until +911 post BMT; median: 160 days), residual host cells were detected in all but three patients. Persistence of host cells in the early phase post-BMT was mostly transient and probably due to long term surviving host T-lymphocytes. Reappearance of host cells several months after BMT is highly suspicious of relapse from the underlying malignancy. Due to its high sensitivity, PCR is a valuable tool in monitoring the switch from recipient to donor cell population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486128 TI - Agarose electrophoresis of DNA in discontinuous buffers, using a horizontal slab apparatus and a buffer system with improved properties. AB - Using a horizontal slab apparatus with a buffer in the reservoirs at the level of the gel ("sea-level electrophoresis"), the retrograde discontinuous buffer system reported by Wiltfang et al. for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of proteins was applied to DNA electrophoresis. This application yielded the advantages of an increased displacement rate of the moving boundary front and a decrease in the concentration of the counterion base in the resolving phase, which yielded reduced relative mobility values at equivalent gel concentrations and practicable low buffer concentrations. The change of relative mobilities (Rf) with a variation of field strength is decreased compared to that of the migration rate in the continuous Tris-boric acid-EDTA (TBE) buffer and thus the robustness of the system is improved, as well as the efficiency of separation. The system of Wiltfang et al. has in common with previously described discontinuous DNA system, that it is able to stack DNA from dilute samples and is insensitive to sample components with lower net mobilities than DNA, such as acetate. However, the variance of Rf at constant current density in the discontinuous buffer system is not improved over that of the migration rate at constant field strength in the continuous TBE buffer. PMID- 8486129 TI - DNA shape and separation efficiency in polymer media: a computerized method based on electrophoretic mobility data. AB - The computer program ELPHOFIT for evaluation of the nonlinear plots of log (mobility) vs. polymer concentration (Ferguson plots) in terms of molecular and polymer properties has been extended to yield a measure of the molecular sieving capacity of the polymer medium. The usefulness of the extended program, version 2.2, was exemplified by the evaluation of DNA shape and separation efficiency in solutions and gels of agarose and polyacrylamide, using previous reports in the literature as a data base. That application of the extended program yields the following results:(i) The size of migrating DNA can be compared with an equivalent sphere having the same free mobility for a particular set of experimental conditions. The decrease in size of the equivalent sphere with polymer concentration previously demonstrated for agarose solutions applies to all of these polymer media; it reveals a steep, hyperbolic decline of that radius in uncrosslinked polyacrylamide solutions in contrast to the shallow decline in the other three media. (ii) The separation efficiency of polyacrylamide gels exceeds that of uncrosslinked polyacrylamide solutions; the separation efficiency of agarose solutions for DNA smaller than 1 kb in length is higher than that of polyacrylamide solutions. Program ELPHOFIT 2.2 is available on request from the first author. PMID- 8486130 TI - On the kinetics of photopolymerization: a theoretical study. AB - In dye-sensitized polymerization, some paradoxical phenomena have been found, such as an anomalous decrease of reaction rate with decrementing thicknesses of the gelling layers. By mathematical modelling, and experimental verification, it has been found that high incorporation efficiencies (> 95% conversion of monomers into the growing polymer) can only be obtained at the correct levels of dye in the gelling solution and by using the proper light intensity. Paradoxically, if levels of sensitizer or incident light intensities are too high, the rate of photosensitizer consumption is too high, as compared with the rate of monomer incorporation, so that dye depletion occurs prior to chain elongation, and the reaction suddenly comes to a stop. In methylene-blue catalysis, the curve correlating the monomer incorporation with the catalyst concentration exhibits a maximum, indicating poor conversions both below and above a critical catalyst level. When correctly used, photopolymerization still offers unique advantages over chemical (persulfate) polymerization, such as absence of oxidizing conditions and control at the onset of reaction, while guaranteeing high conversion efficiencies (> 95%). PMID- 8486131 TI - On the use of dimensionless parameters in acid-base theory. II. The molar buffer capacities of bivalent weak acids and bases. AB - It is shown that stoichiometric rather than thermodynamic dissociation constants can and should be used in the buffer capacity theory. The mean valence of bivalent weak acids and bases is deduced in a form with dimensionless parameters. The expressions for the molar buffer capacities of bivalent weak acids and bases are identical with that for a bivalent ampholyte, and the theory for the latter given earlier is thus valid in all details for bivalent weak acids and bases. PMID- 8486132 TI - Counterflow in isotachophoresis: computer simulation and experimental studies. AB - A computer model has been developed to predict the effects of co- and counter current flows on electrophoretic transport. Model predictions are compared with experimental data obtained with the large-scale recycling isotachophoresis apparatus, recently developed in our laboratory. There were no significant changes in the steady state properties or the transient development of the Kohlrausch-adjusted profiles with and without flow. The application of counterflow in free flow isotachophoresis in early stages, before a steady state is achieved, can result in selective wash-out of slower sample components. Thus, the magnitude of counterflow can be used as a variable in optimizing separations. The characteristic features of the model render it also suitable for the simulation of electroosmotic flow in capillary electrophoresis in open tubes, where plug-type flow prevails. PMID- 8486133 TI - Concanavalin A crossed affinoimmunoelectrophoretic analysis of the major pig serum proteins during fetal development. AB - The interaction between concanavalin A (Con A) and alpha-fetoprotein (AFP), transferrin (TF), fetuin, alpha 1-antitrypsin (AT) and alpha 1-acid glycoprotein (AGP) has been analyzed by crossed affinoimmunoelectrophoresis (CAIE) in fetal extracts or sera, from 26-day-old porcine fetuses to birth, and in adult pigs. Most of the TF and AFP (100 and 85-90%, respectively) reacted with Con A during the entire developmental period. AGP showed both two reactive and one nonreactive Con A isoforms, whose proportions change greatly during development. In younger fetuses 100% of the protein was Con A-nonreactive. This variant represented 64% in 50-day-old fetuses, 80% in newborn pigs and 20% in adult sera. Fetuin and AT showed a maximum of three Con A-reactive microforms and one Con A-nonreactive microform, which was always a minor form. These microforms were detected mainly in young fetuses. Although the proportion of Con A-reactive variants of fetuin and AT changes during fetal development, the predominant microform was always that with intermediate affinity against Con A. The same microform was also predominant in adult AT, whereas the more reactive microform in respect to Con A predominates in adult fetuin. PMID- 8486134 TI - Use of fluorogenic substrates to visualize trypsin and chymotrypsin inhibitors after electrophoresis. AB - Fluorogenic substrates were tested as a means of increasing both the sensitivity and the selectivity of trypsin and chymotrypsin inhibitor detection after electrophoretic separation. Out of six substrates applied to cellulose acetate membranes, N alpha-benzyloxycarbonyl-L-arginine-4-methylcoumarinyl-7-amide (Z-Arg MCA) and benzyloxycarbonyl-glycyl-glycyl-L-arginine-4-trifluoromethylcoumariny l 7-amide (Z-Gly-Gly-Arg-TFMCA) were found to be suitable for trypsin, and L-alanyl L-alanyl-L-phenylalanine-4-methylcoumarinyl-7-amide (Ala-Ala-Phe-MCA) was suitable for chymotrypsin. A procedure to detect trypsin and chymotrypsin inhibitors, and to discriminate between them, was developed. After electrophoresis, slab gels were first incubated with the enzyme (bovine trypsin, bovine chymotrypsin, or human duodenal juice) at 37 degrees C, and then covered with the respective substrate membrane and incubated at room temperature while being observed under UV light. Dark blue inhibitor bands on a light-blue fluorescent background were obtained with Z-Arg-MCA/trypsin and Ala-Ala-Phe MCA/chymotrypsin, whereas Z-Gly-Gly-Arg-TFMCA/trypsin resulted in dark inhibitor bands on a fluorescent green background. The "inhibitor overlay membrane technique" (IOM technique) was used after polyacrylamide gel isoelectric focusing with carrier ampholytes and immobilized pH gradients, pore-gradient polyacrylamide gel electrophoresis, and sodium dodecyl sulfate pore-gradient polyacrylamide gel electrophoresis. PMID- 8486135 TI - Pattern variations of polyclonal and monoclonal immunoglobulins of different isotypes analyzed by high-resolution two-dimensional electrophoresis. AB - High-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used to analyze serum samples and purified immunoglobulins (Ig) obtained from "normal" individuals and from patients diagnosed with monoclonal gammopathies (MG) (n = 47; 5 IgA, 15 IgM, 15 IgG, 4 biclonal IgG, 1 IgD, 7 Bence Jones proteins). Polyclonal and monoclonal heavy (H) chains were located at different restricted gel positions according to their isotype. Monoclonal H chains appeared as sets of spots characterized by charge (pI) and size (M(r)) microheterogeneity. Most of the monoclonal gamma chains were not seen on the gels (12/15). Supplementary polypeptides of 45-48 kDa were detected in serum samples containing monoclonal IgM, but were not seen in MG of other isotypes. However, these polypeptides were not specifically associated with monoclonal IgM because they were also found on protein maps of purified polyclonal IgM. Polyclonal light (L) chains appeared as cloudy bands containing several zones of higher density, whereas monoclonal L chains were usually resolved as single sharp spots. In 6 samples, monoclonal L chains were not seen, and in 9 samples, they appeared as two or more spots, characterized by different pI and/or M(r). In one sample obtained from a patient with a biclonal gammopathy, the L chains were resolved as 4 different spots. Our results confirm that 2-D PAGE is an excellent tool to study Ig. Analysis of the L chain region of the gels was particularly informative. Several monoclonal L chains exhibited heterogeneous two-dimensional spot patterns, suggesting that "subtile" clonal mutations of B-cell lineage and/or posttranslational modifications were involved in their production. PMID- 8486136 TI - Subtyping of alkylated human orosomucoid: evidence for a duplicated gene, ORM1*F2S. AB - Isoelectric focusing of human orosomucoid (ORM) was studied following different sample treatment. It is shown that: (i) alkylation with iodoacetamide leads to a drastic change in the isoelectric point (pI) of both ORM1 F2 and ORM2 A gene products and greatly improves the discrimination between ORM1 F1 and ORM1 F2; (ii) previous reduction of the molecule with dithiothreitol partially inhibits the pI transitions with resultant artifactual ORM1 F1F2S patterns that correspond in most cases to F2S phenotypes. With the technique now described, the persistence of three ORM1 gene products was found in only one individual and the segregation analysis is consistent with the existence of a rare ORM1*F2S haplotype. PMID- 8486137 TI - Bronchoalveolar lavage fluid proteins in human lung disease: analysis by two dimensional electrophoresis. AB - Proteins of human bronchoalveolar lavage fluids, obtained by washing the epithelial lining fluid of the lungs with phosphate-buffered saline, were analyzed by two-dimensional electrophoresis under denaturating and reducing conditions. The two-dimensional pattern of bronchoalveolar lavage fluid proteins of healthy volunteers (controls) were compared with those of patients with idiopathic pulmonary fibrosis, sarcoidosis, and asbestosis. Particular interest was paid to the proteins present in minor amounts mainly in the low molecular weight region of the gels. Marked changes in single protein spots were observed. In idiopathic pulmonary fibrosis the spot intensity of the surfactant-associated protein, SP-A, showing isomeric forms both in charge and in molecular weight, was markedly decreased. In sarcoidosis, the immunoglobulins (IgG, IgA) and a group of protein spots at an isoelectric point of 4.5-5.0 and a molecular mass of 55 kDa were increased. An additional spot appeared at an isoelectric point of 4.5 and a molecular mass of 12 kDa. In particular in asbestosis, but also in some cases of idiopathic pulmonary fibrosis and sarcoidosis, the number and intensity of low molecular weight proteins were increased strongly. PMID- 8486138 TI - Clonal imbalances of plasma/serum immunoglobulin production in infants. AB - To study the clonal events occurring during ontogeny of the humoral immune system, we evaluated plasma immunoglobulin (Ig) production in term newborns and young children by high-resolution two-dimensional gel electrophoresis. The clonality pattern of Ig light (L) chains from healthy newborns (n = 19) was similar to that observed on protein maps of their mothers or of normal adults (n > 100), that is, rare distinguishable small spots in a cloud-like large band of indiscrete Ig L chain spots (polyclonal pattern; maternal Igs). Analysis of plasma samples obtained from infants between 1 month and 5 years of age (n = 55) revealed discrete but evident alterations of the clonality of Ig production. Between the 2nd and 4th months of life, transient attenuation of the "polyclonal background" was observed in association with the appearance of an increasing number of well-resolved Ig L chain spots (corresponding to plasma Ig concentrations between 0.5 and 1 g/L per spot). This "restricted" clonal pattern was progressively less apparent on protein maps of infants older than 2 year and evolved towards a "normal" adult polyclonal pattern at the age of 5. These results suggest that the development of the B-cell clones is heterogeneous, either through limited outgrowth of precursor cells or through selective antigenic pressures. PMID- 8486139 TI - Nephropharmacology. PMID- 8486140 TI - Factors influencing drug protein binding in patients with end stage renal failure. AB - Investigations were undertaken to evaluate which uraemic solutes decrease drug protein binding. This was done by performing HPLC-fractionation of uraemic biological fluids and studying the effect of addition of a lyophilisate of each fraction to normal plasma containing standard quantities of radiolabelled drugs. From a first study, based only on fractionation of uraemic ultrafiltrate with an HPLC-gradient mainly aimed at elution of hydrophilic compounds, hippuric acid appeared to be a major protein binding inhibitor for theophylline and phenytoin. The problem with this approach was that it did not include the compounds with the most substantial protein binding. Therefore, studies were planned to fractionate deproteinized uraemic sera, but first it was necessary to define which deproteinisation methods gave the highest yields of protein bound ligand. Heat denaturation was found to be one of the most effective deproteinisation methods. When a lyophilisate of uraemic serum, deproteinised by this method, was added to normal plasma, a higher capacity to displace theophylline from protein binding sites was found compared to the effect of an identical volume of an ultrafiltrate of the same samples. Fractionation of the deproteinised sample by HPLC revealed a larger number of fractions able to inhibit drug protein binding. PMID- 8486141 TI - Population kinetics of gentamicin in neonates. AB - A population kinetic analysis was carried out on sparse plasma gentamicin (GE) concentration data from 469 neonates obtained as part of a routine therapeutic drug monitoring (TDM) programme in the hospital neonatology unit. The best predictors of the kinetic parameters of the monoexponential model, volume of distribution (Vd) and clearance (CL), were the weight (WT) and gestational age (GA). Vd of the neonates was only related to WT, whereas the half-life was only related to the GA. The clinical implications of the findings are that the initial dose per WT administered to premature infants should be larger than that for term infants, because of a larger Vd per unit WT, and the intervals between maintenance doses should extended due to the prolonged half-life. Apart from these general guidelines, specific dose recommendations are also given. PMID- 8486142 TI - Nonlinear kinetics and the 1-exp function in nephropharmacology. AB - The basic law in nephropharmacology states that pharmacokinetic parameters depend linearly on renal function. Few exceptions to linear dependence have been reported, e.g. substances with saturable tubular reabsorption or secretion. A further example is cyclosporin, which was found to be eliminated according to log concave nonlinear kinetics in 3 patients with hepatotoxicity after kidney transplantation. The nonlinear cyclosporin kinetics were computer-fitted to the integrated forms of the 1-exp function and the Michaelis-Menten equation by nonlinear regression analysis. The same maximal velocity (Vmax = 23 ng ml-1 h-1) and Michaelis constant (Km = 686 ng ml-1) were calculated for cyclosporin when applying either the 1-exp function or the Michaelis-Menten equation. The nonlinear elimination of cyclosporin, however, was described even more closely by the 1-exp function than by the Michaelis-Menten equation. PMID- 8486143 TI - Diuretic action of potassium channel blockers. AB - The availability of specific potassium channel blockers has made it possible to examine their effects along the nephron on fluid and electrolyte excretion. Recent experiments indicate that they modulate transepithelial sodium and potassium transport. In the thick ascending limb, potassium channel blockers, by interfering with potassium recycling across the apical cell membrane, reduce the activity of the sodium-2chloride-potassium cotransporter. In the initial and cortical collecting duct their inhibitory action on ATP-sensitive potassium channels reduces potassium secretion. Accordingly, tissue-specific potassium channel blockers are promising diuretic agents that may induce diuresis by inhibiting tubular sodium transport with only minimal loss of potassium. PMID- 8486144 TI - Elimination of cefmenoxime during continuous haemofiltration. AB - The elimination of cefmenoxime after single and repeated i.v. dosing was studied in 12 patients with severe renal failure and sepsis during continuous haemofiltration. More than 30% of the drug was found in the filtrate. The sieving coefficient (S) was 0.54. Vss% was unchanged 0.31 l.kg-1 in comparison with patients with normal renal function, whereas the mean t1/2ss was prolonged to about 16 h, and total clearance was reduced 20.8 ml.min-1.1.73 m-2. Once daily administration of 1 g cefmenoxime is suggested as the appropriate dose under such circumstances. PMID- 8486145 TI - Shedding and repair of renal cell membranes following drug-induced nephrotoxicity in humans. AB - Nephrotoxic drugs may account for approximately at least 20% of clinically observed cases of acute renal failure in whom tubular lethal or sublethal damage is a predominant finding. Acute toxic tubular cell injury is characterized by loss of cellular polarization, intrinsic energy deficiency, calcium overload, release of toxic proteases and free oxygen radicals, derangement of the cytoskeleton, and vacuolar transformation of brush border microvilli. These events may finally lead to irreversible cell death. Shedding of membrane enzymes and cytoskeletal components in urine (kidney tissue proteinuria) may serve as a noninvasive early marker for assessing tubular cell injury. Successful recovery of renal function depends on early repair of lethally or sublethally damaged nephrons, in which intrinsic nephrogenic adaptive and proliferative responses cooperate in concert with auto/para/-juxtacrine growth promoting factors and cytokines. Exogenously administered growth factors may enhance renal cell recovery, as shown in animal models. Increased expression of immediate early genes in tubular cells after renal injury reflects the ongoing mitogenic activity necessary for reepithelialization and remodeling (new, polarized, differentiated cells). Further progress in understanding the molecular mechanisms of renal tubular injury will probably influence the diagnostic modalities and therapeutic approaches to acute drug induced renal failure. PMID- 8486146 TI - Evaluation of nephrotoxicity with renal antigens in children: role of Tamm Horsfall protein. AB - Renal antigens are proteins that originate from the kidney and are detectable in urine by immunological techniques. After renal injury cell fragments are shed and appear in urine. Thus, the appearance of cellular fragments represents acute damage to renal cells caused by various means. With this approach proximal tubular cell injury can be detected using the proteins intestinal alkaline phosphatase (IAP) a brush border enzyme, or villin, a protein of the cytoskeleton. Both proteins have been found in urine from children receiving immunosuppressive treatment, including ifosfamide and aminoglycosides. In contrast, Tamm-Horsfall protein (THP) is an actively secreted protein that has been found by mRNA-analysis to occur only in the kidney. Immuno-reactivity to THP is restricted to the ascending loop of Henle and the early distal tubule. In human fetal specimens, THP expression was consistently found in the 16th week of gestation. In amniotic fluid THP was detectable after the 20th week, rising to a median value of 1.3 mg.l-1 at birth. In disturbed pregnancies with the feto-fetal transfusion syndrome, THP was not detectable, indicating reduced tubular THP secretion and renal function. Postnatally, THP excretion increases steadily, reaching a maximum in early adulthood. THP-excretion is low immediately after renal transplantation, reflecting acute renal failure in the early phase of transplantation, and increases to a normal values two to three weeks later. In severe diabetic ketoacidosis THP excretion is extremely low, with partial recovery 12 days later. The combination of low THP excretion and high proximal tubular enzyme release indicates both proximal (renal cortical) and distal tubular (renal medullary) damage in diabetic ketoacidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486147 TI - Partial and complete de Toni-Debre-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy. AB - Ten out of 79 patients treated with ifosfamide (IFO) developed a complete (n = 2) or partial (n = 8) de Toni-Debre-Fanconi syndrome (RFS). All but one of these patients had been treated in addition with cisplatinum (CPL) or had undergone radiotherapy to the abdomen or nephrectomy as part of the overall treatment for malignancy. A detailed nephrological work-up of proximal tubular function showed decreased fractional phosphate and percent aminoacid reabsorption in 37.1 and 56.7% of cases, respectively, and the excretion of alpha 1-microglobulin and N acetyl-beta-D-glucosaminidase was elevated in 44.4 and 23.5%. Glomerular function was well preserved in the majority of patients. Tubular dysfunction was confirmed by silver-stained SDS PAGE of urine which showed mostly low molecular weight proteinuria. CPL has been shown to result in renal magnesium loss and reduced glomerular filtration rate, and its toxicity clearly differs from IFO-mediated tubulopathy. Our data suggest that subclinical impairment of proximal tubular function was significantly increased by additional CPL therapy. We conclude that CPL may enhance IFO-mediated nephrotoxicity and that a substantial number of patients is at risk of developing persistent tubular dysfunction leading to metabolic bone disease. PMID- 8486148 TI - Effect of antihypertensive drugs on glomerular hyperfiltration and renal haemodynamics. Comparison of captopril with nifedipine, metoprolol and celiprolol. AB - Glomerular hyperfiltration and hypertension may contribute to the progression of chronic renal insufficiency regardless of the underlying disease. Protein restriction and antihypertensive treatment are used to slow the decline in renal function. However, little is known about the interaction of protein loading and antihypertensive treatment on glomerular haemodynamics in humans. This paper compares the renal haemodynamic effects of beta-adrenoceptor blockers with those of the calcium channel antagonist nifedipine and the ACE inhibitor captopril on resting glomerular filtration and during glomerular hyperfiltration. In two separate studies the effects of nifedipine, captopril, metoprolol, and celiprolol on renal haemodynamics have been investigated. In two groups of healthy volunteers (n = 13) inulin and PAH clearances were measured, first under fasting conditions and afterwards during aminoacid infusion. In fasting subjects nifedipine and metoprolol induced glomerular hyperfiltration, while celiprolol and captopril did not significantly affect GFR. Without premedication, and also after nifedipine, metoprolol and celiprolol, the aminoacid infusion significantly increased the GFR. After premedication with captopril, however, aminoacid-induced hyperfiltration was prevented. In fasting subjects captopril, celiprolol and metoprolol elevated PAH clearance. With our without premedication aminoacid infusion increased renal plasma flow compared to baseline on the control day. We conclude that in healthy subjects, acute administration of antihypertensive drugs results in different renal haemodynamic responses. In contrast to captopril and celiprolol, nifedipine and metoprolol induce glomerular hyperfiltration like protein loading. Thus, they may counteract the renal haemodynamic effects of protein restriction. Celiprolol behaves similarly to captopril, since it increases renal perfusion without inducing glomerular hyperfiltration, a pattern which might reflect lower glomerular pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486149 TI - Low-dose segmental blockade of the nephron rather than high-dose diuretic monotherapy. AB - The specific renal effect of diuretics is due to the fact that their concentrations is almost 100-fold greater in the renal tubule than in the plasma. The function of the different segments of the nephron may be altered following changes in the effective arterial blood volume (EABV) and the extracellular fluid volume (ECFV). In diseases with reduced EABV, e.g., congestive heart failure, decompensated cirrhosis of the liver, and the nephrotic syndrome, proximal tubular hyperreabsorption of sodium occurs, leaving only a low Na+ load in the distal segments of the nephron, the site of diuretic action. Clinically, the response to diuretics is reduced or resistance to diuretics may even ensue, which can be predicted by a FENa < 0.2%. Resistance to diuretics can be overcome by short-term comedication with acetazolamide, which increases Na+ delivery to the site of action of the other diuretics used concomitantly. In states with increased ECFV, e.g. in chronic renal failure, there is distal tubular Na+ rejection, leading to a greater increase in FENa the more GFR is reduced. The remaining intact nephrons present a relatively increased response to diuretics. The efficacy of diuretic treatment in renal failure can be optimised by combining loop diuretics with thiazides. In conclusion, low-dose combination therapy, inducing "segmental blockade of the nephron", meets the functional changes along the nephron. It is therefore more effective and safer than high-dose monotherapy. PMID- 8486150 TI - Receptors for mammalian steroid hormones in microbes and plants. AB - Steroids are of universal occurrence, present variously as cell wall constituents and bioregulators. A number of bacteria, fungi, and photosynthetic vascular plants synthesize steroids that are hormonally active in the animal world. The cellular effect of such steroids in microbes and plants appears by and large to be comparable to that in mammals. Available evidence suggests that steroid action in botanical phyla is mediated via receptors organized in a manner similar to that seen in animals. Therefore, the ancestry of ligand induced transactivation via zinc finger proteins appears to date farther back than the early Cambrian burst of metazoan evolution 500 million years ago. PMID- 8486151 TI - N-peptidyl-O-carbamoyl amino acid hydroxamates: irreversible inhibitors for the study of the S2' specificity of cysteine proteinases. AB - A series of new inhibitors for cysteine proteinases with the general structure Z Phe-Gly-NHO-CO-Aa (Aa = amino acids) was synthesized and tested as inhibitors of papain-like enzymes (cathepsins S, L, B and papain). Like N-peptidyl-O-acyl hydroxamates the inhibitors inactivate cysteine proteinases by a sulfenamidation of the active site cysteine residue. The most effective inhibitors display second order-rate constants of inactivation in the range of 10(3)-10(4) M-1.s-1. Since the structure of the N-peptidyl-O-carbamoyl amino acid hydroxamates allows the variation of the leaving group this class of inhibitors was used as a new tool for evaluation of the S2' specificity of cysteine proteinases. PMID- 8486152 TI - Membrane interaction of Escherichia coli penicillin binding protein 5 is modulated by the ectomembranous domain. AB - E. coli penicillin binding protein (PBP) 5 is anchored to the periplasmic face of the inner membrane by a C-terminal domain which is predicted to form an amphiphilic alpha-helix. Here we show that the presence of a substrate analogue, benzyl penicillin, causes the protein to be converted from a membrane bound urea inaccessible form to a urea extractable form. If the anchor region is fused to the periplasmic protein, beta-lactamase, the fusion protein becomes membrane bound but is unable to exhibit the changes in urea extractability which are observed with PBP5. We therefore conclude that although the C-terminus of PBP5 is sufficient to anchor the protein to the membrane surface the ectomembranous domain can affect the state of the anchor and in vivo changes in the state of anchoring may be related to enzyme activity. PMID- 8486153 TI - Induction of GTP cyclohydrolase I by bacterial lipopolysaccharide in the rat. AB - A 2- to 3-fold increase of GTP cyclohydrolase I (E.C. 3.5.4.16), the key enzyme of tetrahydrobiopterin biosynthesis from GTP, was observed in cerebellum, remaining brain, liver, spleen, and adrenal gland of rats treated with a single dose of lipopolysaccharide (LPS). This led to increased biopterin levels in tissues but not in plasma. Parallel induction of nitric oxide (NO) synthase was indicated by a 10- to 100-fold increase of plasma nitrate levels 6 and 12 hours after injection of LPS. Furthermore, systolic blood pressure was reduced significantly by 23%. Our results demonstrate induction of tetrahydrobiopterin biosynthesis after LPS treatment in vivo. PMID- 8486154 TI - Prolyl oligopeptidase catalysis. Reactions with thiono substrates reveal substrate-induced conformational change to be the rate-limiting step. AB - Prolyl oligopeptidase, a member of the new family of serine proteases, exhibits significant mechanistic differences compared with the enzymes of the chymotrypsin and subtilisin families. Our kinetic study using the thiono substrate, benzyloxycarbonyl-Gly-Pro[CS-NH]-2-naphthylamide suggests that the putative oxyanion binding site is important in prolyl oligopeptidase catalysis, although to a lesser extent than in the chymotrypsin- and subtilisin-catalyzed reactions. By using another thiono substrate, benzyloxycarbonyl-Gly[CS-NH]Pro-2 naphthylamide, it is demonstrated that the distant S2P2 hydrogen bond (formed between the S2 subsite and P2 peptide residue) makes a greater contribution to catalysis than does stabilization by the oxyanion binding site involved directly in the bond cleavage. In contrast to the reactions catalyzed by chymotrypsin and subtilisin, no kinetic deuterium isotope effect is apparent in the acylation of prolyl oligopeptidase measured either with the specific benzyloxycarbonyl-Gly-Pro 2-naphthylamide, or with the very poor substrate, benzyloxycarbonyl-Gly-Pro[CS NH]-2-naphthylamide. This indicates that the rate-limiting conformational change is induced by the substrate. PMID- 8486155 TI - Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin activated human monocytes. AB - Tissue factor (TF) is a transmembrane glycoprotein which, in association with factor VII(a), is the main activator of coagulation. In illnesses such as Gram negative endotoxemia, circulating monocytes synthesize and express substantial TF activity, resulting in extensive disseminated intravascular coagulation. We investigated the way in which TF is suppressed by pentoxifylline (PTX), and found that PTX down-regulates immunologic TF expression and specific mRNA production in response to LPS. Since TF mRNA stability is not altered, this effect appears to take place at the transcriptional level. PMID- 8486156 TI - Zeta-crystallin versus other members of the alcohol dehydrogenase super-family. Variability as a functional characteristic. AB - Species variability of the lens protein zeta-crystallin was correlated with those of alcohol dehydrogenases of classes I and III and sorbitol dehydrogenase in the same protein family. The extent of overall variability, nature of residues conserved, and patterns of segment variability, all fall within the limits typical of the 'variable' group of medium-chain alcohol dehydrogenases. This shows that zeta-crystallin is subject to restrictions similar to those of classical liver alcohol dehydrogenase and therefore derived from a metabolically active enzyme like other enzyme crystallins. Special residues at the active site, however, differ substantially, including an apparent lack of a zinc-binding site. This is compatible with altered functional properties and makes the spread within this medium-chain dehydrogenase family resemble the wide spread within the short chain dehydrogenases. Schematic plotting is useful for illustrating the differences between 'variable' and 'constant' enzymes. PMID- 8486157 TI - Chemical modification of rat liver cytosolic NADP(+)-linked isocitrate dehydrogenase by N-ethylmaleimide. Evidence for essential sulphydryl groups. AB - Incubation of rat liver cytosolic isocitrate dehydrogenase with N-ethylmaleimide (NEM) resulted in the inactivation of the enzyme following pseudo-first order kinetics. Isocitrate affords considerable protection against inactivation whereas NADP+ enhances modification of the enzyme, suggesting localization of the modified group at the active site. Correlation of loss of activity with incorporation of [14C]NEM indicated that two sulphydryl residues/sub-unit are modified of which only one is shown to be involved in catalysis. pH dependence of the inactivation process implicates a reactive group of pKa 8.1 in catalysis. We conclude that a unique cysteine residue is essential for maximal catalytic activity of isocitrate dehydrogenase. PMID- 8486158 TI - Phase transitions of Acholeplasma laidlawii membranes. The involvement of Mg(2+) ATPase in the C transition. AB - Highly sensitive differential scanning calorimetry has been employed to study the phase transitions of A. laidlawii membrane. The DSC curves obtained show five distinct transitions between 20 and 80 degrees C which contain a reversible lipid thermotropic transition at about 37 degrees C and four irreversible denaturation transitions of the membrane proteins occurred at about 44 degrees C, 52 degrees C, 62 degrees C, and 67 degrees C, respectively. Total enthalpy of the thermal denaturation of membrane proteins is 3.4 +/- 0.5 cal/g. Further study of A. laidlawii membrane preparations by means of thermal gel analysis and enzyme activity measurements at various temperatures provided information that the third peak (C transition) of the DSC curve involved primarily with Mg(2+)-ATPase on A. laidlawii membranes. PMID- 8486159 TI - Metabolism of exogenous ganglioside GM1 in cultured cerebellar granule cells. The fatty acid and sphingosine moieties formed during degradation are re-used for lipid biosynthesis. AB - Cerebellar granule cells, differentiated in vitro, were parallelly fed with [Sph 3H]GM1 and [stearoyl-14C]GM1, under identical conditions (10(-6) M ganglioside; pulse, from 1-4 h; chase, up to 24 h after 4 h pulse) and the salvage pathways of sphingosine and stearic acid were investigated. It was observed that both sphingosine and stearic acid, liberated during the intralysosomal degradation of ganglioside, are metabolically recycled, along distinct pathways. Sphingosine is used for the biosynthesis of a number of sphingolipids, particularly ceramide, glucosyl-ceramide, gangliosides and sphingomyelin; stearic acid is utilized for the biosynthesis of sphingolipids, and to a greater extent, glycero phospholipids, especially those endogenously richer in stearic acid (phosphatidyl ethanolamine and phosphatidyl-choline). No evidence was provided for a salvage pathway for ceramide. PMID- 8486161 TI - A 31P NMR study of the interaction of the antitumor active metallocene Cp2MoCl2 with calf thymus DNA. AB - Treatment of sonicated calf thymus DNA with the antitumor active metallocene Cp2MoCl2 afforded a metallocene-DNA complex which was characterized by 31P NMR spectroscopy. In addition to the resonance for the phosphate backbone (delta 1.6), the spectrum contained 2 signals assigned to a phosphate bound Mo-DNA complex(es) (delta 37.2, 36.5) and a broad signal at delta 6.2 ppm. This result suggests that covalent attachment of the metallocene Cp2MoCl2 occurs via phosphate(O) coordination and is accompanied by local distortion of the DNA backbone. This result supports recent ICP studies with Cp2TiCl2 that have DNA detected DNA-metallocene adducts. PMID- 8486162 TI - Beta-oxidation of unsaturated fatty acids in humans. Isoforms of delta 3, delta 2 enoyl-CoA isomerase. AB - This investigation was undertaken in order to elucidate the human enzymes which participate in metabolism of the double bonds of unsaturated fatty acids during beta-oxidation. The results indicate that the human monofunctional delta 3, delta 2-enoyl-CoA isomerase (EC 5.3.3.8) with the native M(r) of 70,000 differed significantly from its rat counterpart [Palosaari et al. (1990) J. Biol. Chem. 265, 3347-3353]; the isoelectric point of the human isoform was over three pH units more acidic, it showed different chromatographic behaviour, the human enzyme did not show any clear-cut substrate chain-length specificity and only a weak immunological cross-reactivity was detected with the antibody to rat liver mitochondrial short-chain enzyme. This explains the failure of attempts to apply the rat data directly to human beings. Another isomerase activity from human liver was found to be a part of the isomerase-hydratase-dehydrogenase polypeptide showing immunological cross-reactivity with the previously characterized peroxisomal multifunctional enzyme (MFE) from rat liver. PMID- 8486160 TI - Autostimulation of the DnaK (HSP 70) ATPase of Escherichia coli. AB - The ATPase activity of DnaK, the 70-kDa chaperone of Escherichia coli, is stimulated by an unfolded protein. However, the stimulation of the DnaK ATPase by unfolded bovine pancreatic trypsin inhibitor can only be observed at low DnaK protein concentrations. At higher DnaK concentrations, the ATPase activity of DnaK cannot be stimulated by the addition of unfolded bovine pancreatic trypsin inhibitor. This is a consequence of the autostimulation of the DnaK ATPase at higher DnaK concentrations. The autostimulation of DnaK is reflected by a non linear dependence of ATP hydrolysis on DnaK concentration. Furthermore, DnaK exists as a mixture of monomers and dimers in equilibrium, and the dimers dissociate into monomers in the presence of ATP. PMID- 8486163 TI - Relative stability of AT and GC pairs in parallel DNA duplex formed by a natural sequence. AB - The low-cooperative melting of parallel DNA formed by a natural 40 bp long sequence from Drosophila: 5'-d(TGATTGATCGATTGTTTGCATGCACACGTTTTTGTGAGCG)-3' 5' d(ACTAACTAGCTAACAAACGTACGTGTGCAAAAACACTCGC)-3' that possesses a normal nucleotide content was studied by using the special method of measuring the fluorescence of its complex with acriflavine as well as by conventional thermal denaturation. Acriflavine allows discrimination of the melting of AT and GC pairs because its fluorescence is quenched by neighbouring G bases. We have observed that about 40% of AT pairs melt at 14 degrees C while the remainder melt at 42 degrees C. The GC pairs remain stable up to approximately 40 degrees C and melt at 54 degrees C. The higher stability of GC pairs suggests the formation of cis Watson-Crick pairs in parallel DNA. PMID- 8486164 TI - d-alpha-Tocopherol inhibits low density lipoprotein induced proliferation and protein kinase C activity in vascular smooth muscle cells. AB - Native and malondialdehyde modified low density lipoproteins have been shown to stimulate smooth muscle cell proliferation (A7r5) in vitro. The stimulation is associated with an increase of protein kinase C activity. d-alpha-Tocopherol, at physiological concentrations, has been found to inhibit both protein kinase C activity and cell proliferation. PMID- 8486165 TI - Electron microscopic study of compaction of individual DNA molecules with histone H1 in surface films. AB - Interaction of individual spread DNA molecules with histone H1 was studied by electron microscopy using the protein-free spreading technique. It was shown that in the presence of 0.2-5 micrograms/ml of histone H1 in hypophase there are three types of structures in electron-microscopic preparations: fibres of non-compacted DNA, compact fibres with twisted strands of duplex DNA and compacted rod-like and circular structures where the separate fibres of duplex DNA could not be distinguished. The study of compact structure morphology allows us to conclude that they are formed by side-by-side association of DNA fibres. At an increase of ionic strength there is a tendency for transition from the second to the third type structures. The latter can be explained by transition from non-cooperative to cooperative binding of histone H1 to DNA. Regularities established for interaction between DNA and histone H1 can be useful for understanding the role of histone H1 in the higher order structure organization of chromatin. PMID- 8486166 TI - Assessment of the implantation site by transvaginal ultrasonography. AB - OBJECTIVE: To investigate the implantation site in a singleton pregnancy. DESIGN: Transvaginal ultrasonography (US) was performed at the mid or late follicular phase and/or at very early gestation before 6 weeks. SETTING, PATIENTS: Ultrasound monitoring was performed on 21 women with spontaneous cycles or treated by administration of 2.5 mg/d bromocriptine mesylate (Parlodel; Sando Co., Tokyo, Japan) for occulted hyperprolactinemia at the Fertility Clinic of the Department of Obstetrics and Gynecology at Gunma University Hospital. MAIN OUTCOME MEASURES: The site of the ovary with a growing follicle and/or a corpus luteum of pregnancy, and the location of a gestational sac in longitudinal and transverse views were observed. RESULTS: When ovulation occurred in the right ovary, 12 of the 14 gestational sacs were located on the right wall, 1 on the midwall, and 1 on the left wall. Ovulation in the left ovary resulted in 5 gestational sacs located in the left wall and 2 on the midwall. That is, of 21 gestational sacs, 17 were located on the ipsilateral uterine wall to the ovulating ovary, 3 on the midwall, and only 1 on the contralateral. CONCLUSION: Implantation occurs on the ipsilateral uterine wall to the ovulating ovary. PMID- 8486167 TI - Chromosome errors as a cause of spontaneous abortion: the relative importance of maternal age and obstetric history. AB - OBJECTIVE: To evaluate the likelihood of obtaining a chromosome diagnosis in cases of spontaneous abortion (SAB) and of the relative importance of maternal age versus obstetric history in predicting the fetal karyotype. DESIGN: Obstetric history was obtained from all 100 cases of miscarriage in 1 year when products of conception were sent for chromosome studies. Multiple logistic regression analysis was used to calculate odds ratio and statistical significance for correlations between historical factors and the probability of any chromosomal abnormality or trisomy. RESULTS: A chromosome diagnosis was made in 84% of cases. Maternal age was a more important predictor of chromosome abnormality, specifically trisomy, than history of previous livebirths or miscarriages. CONCLUSION: Results from chromosome studies using chorionic villi from SABs are diagnostically useful, even when the patient has a history of repeated miscarriages. PMID- 8486169 TI - Tumor marker CA-125 in tissues of the female reproductive tract and in serum during the normal menstrual cycle. AB - OBJECTIVE: To further elucidate the origin of the physiological CA-125 amounts that lead to cyclic changes in CA-125 serum levels in normally menstruating women. DESIGN: Fifty-three normal endometria, 13 fallopian tubes, 25 ovaries, and nine isolated corpora lutea were prospectively investigated for their CA-125 content in a sandwich solid-phase RIA and by immunohistochemistry. In addition, endometrial CA-125 tissue content was compared with the actual CA-125 serum levels of the study patients. RESULTS: Cytosolic CA-125 concentrations were 20 fold and twofold higher in the endometrium than those measured in the ovary and the fallopian tube, respectively. Moreover, only in the endometrium did CA-125 content show significant cyclic changes, with the highest concentrations during the early proliferative and middle secretory phase. The lowest tissue concentrations were measured during the early secretory phase. Furthermore, during the early and middle secretory phases cytosolic CA-125 was negatively associated with CA-125 serum levels. In immunohistochemistry, marked distributional changes in OC-125 reactivity were revealed in the basalis and the functionalis throughout the menstrual cycle and the postovulatory loss of CA-125 expression was found to be strongly connected with early secretory transformation of glandular epithelium. CONCLUSION: Our findings indicate that the CA-125 amounts responsible for cyclic changes in serum levels in normally menstruating women seem to be a product of normal endometrium. PMID- 8486168 TI - The reproducibility of the revised American Fertility Society classification of endometriosis. AB - OBJECTIVE: To assess the degree of intraobserver and interobserver variability in endometriosis staging using the revised American Fertility Society (AFS) classification of endometriosis. DESIGN: Videotapes of laparoscopies of 20 patients with endometriosis were each scored twice by five observers. SETTING: The reproductive endocrine unit of a tertiary care, university-affiliated hospital. SUBJECTS: Five subspecialty-certified reproductive endocrinologists. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Variability in assigned score was measured for each of the five components of the AFS classification, as well as total scores and stage of endometriosis. RESULTS: There was considerable variability in the scores assigned to each videotape, both by the same observer and by different observers. The grand total score, which ranged from 0 to 90, varied with an SD of 13.44 when a single patient was rated twice by the same observer and varied with an SD of 17.12 when a single patient was rated by two different observers. Among individual components of the score, the greatest variability occurred in endometriosis of the ovary and cul-de-sac obliteration, with less variability observed for peritoneum endometriosis and for ovarian and tubal adhesions. Comparison of intraobserver and interobserver scores resulted in a change in endometriosis stage in 38% and 52% of patients, respectively. There were statistically significant differences in mean endometriosis scores among the observers in four of the five anatomic categories examined. CONCLUSIONS: Intraobserver and interobserver variability was high for ovarian endometriosis and cul-de-sac subscores using the revised AFS classification of endometriosis. PMID- 8486170 TI - Human fetal ovaries and uteri: developmental expression of genes encoding the insulin, insulin-like growth factor I, and insulin-like growth factor II receptors. AB - OBJECTIVE: To study the messenger ribonucleic acid (mRNA) expression of receptors for insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II) in human fetal ovaries and uteri at 10, 15, 19, and 22 weeks' gestation. Insulin, IGF-I, and IGF-II are postulated to have paracrine and autocrine functions in the development of fetal tissues, but receptors for these growth factors have never been studied in reproductive organs of the human female fetus. DESIGN: Ribonucleic acid extracted from human fetal reproductive tissues underwent reverse transcription and polymerase chain reaction (PCR) amplification. The amplified complementary deoxyribonucleic acid (cDNA) fragments were analyzed by gel electrophoresis and restriction enzyme mapping. RESULTS: Messenger RNA expression consistent with both known forms of the insulin receptor, the IGF-I receptor, and the IGF-II receptor was observed in human fetal ovaries and uteri at 10, 15, 19, and 22 weeks' gestation. The identity of the PCR amplified ovarian and uterine DNA fragments were confirmed by digestion with the restriction endonucleases AvaII, DdeI, and BamHI, respectively. CONCLUSIONS: This study demonstrates that mRNA for receptors for insulin, IGF-I, and IGF-II are expressed in the fetal human female genital tract. These receptors may have roles in fetal reproductive tract development. PMID- 8486171 TI - Relative infertility: modeling clinical paradoxes. AB - OBJECTIVES: To assume that a cause of relative infertility will decrease the monthly chance of conception (fecundability) in a dose-dependent manner and, by a mathematical model, to identify common clinical observations and paradoxes that are explainable within this hypothesis. DESIGN: An empirically based assumption of a population-mean fecundability of 0.2 and the accumulating probability of pregnancy equations and projections were used to examine over time the effects of diminishing such fecundability to one half, one fifth, and one twentieth of normal, and then reversing this effect with ideal treatment at points of 2 years and 5 years. RESULTS: [1] The duration of infertility is an important and powerful covariate in determining residual fecundability and the chance of pregnancy, with or without treatment. [2] The more substantial the pathology is, the greater should be the likelihood of pregnancy after its effective treatment. [3] Provided no harm is done by treatment, an increase in subsequent fecundability will result whatever the "dose" of the reproductive disturbance, but this will not always mean that pregnancy is probable. [4] The presence of a second infertility factor should compound dramatically the deleterious effects attributable to the first and make it more likely for either factor to be diagnosed. CONCLUSIONS: Duration of infertility is generally more important than the dose of an infertility factor as a covariate in clinical studies, and more emphasis should be placed on controlling for it. Discouraging clinical reports on the low success of treating certain conditions associated with infertility do not necessarily justify rejecting a hypothesis that such a condition decreases fertility in a dose-dependent manner. PMID- 8486172 TI - Why are couples satisfied with infertility treatment? AB - OBJECTIVE: To determine which factors relate to satisfaction with infertility treatment. DESIGN: A prospective structured interview research design was used. SETTING: In-person and telephone interviews were conducted. PARTICIPANTS: Wives and husbands from 185 couples in southeastern Michigan with primary infertility were studied. MAIN OUTCOME MEASURES: There were two main outcome measures: how satisfied people were with the infertility treatment they received and why they were satisfied. RESULTS: Both men and women were satisfied with the infertility treatment they had received. The most frequently mentioned reasons for satisfaction were the technical skills and the emotional support of infertility specialists. Both men and women advised infertility specialists to be compassionate and share information with their patients. Spouses' satisfaction with treatment was the greatest predictor for both men and women. For men, using escape as a coping skill was a negative predictor for treatment satisfaction. For women, personal control and the number of infertility treatments received were other predictors for treatment satisfaction. CONCLUSIONS: As hypothesized, a variety of psychosocial factors were related to treatment satisfaction. Contrary to expectation, treatment costs and how long respondents had been trying to have a child were not related to treatment satisfaction. This study's results suggest that physicians and their staff should pay particular attention to their patients' emotional needs, to their patients' understanding of procedures explained to them, to discussing adoption with their patients, to involving men more in the infertility treatment, and to assisting women to have more control over their course of treatment. PMID- 8486173 TI - The use of vaginal ultrasound for monitoring endometrial preparation in a donor oocyte program. AB - OBJECTIVE: To determine whether vaginal sonographic measurements can be used to monitor the endometrial preparation of recipients in a donor egg program. DESIGN: Prospective clinical trial. SETTING: University hospital-based IVF and donor egg program. PATIENTS: Twelve women without ovarian function. INTERVENTIONS: [1] In a control cycle, patients received 4 or 8 mg of oral E2 and vaginal ultrasound (US) daily until endometrial thickness > or = 6 mm with a triple-line pattern (favorable endometrium) was seen. Progesterone (P) in oil, 100 mg/d, was then added. [2] An endometrial biopsy was performed on day 7 of P therapy. [3] In a treatment cycle, US monitoring of endometrial development during estrogen (E) administration was used; and ET was performed on the 3rd day of P therapy. RESULTS: In the control cycle, 8 mg/d or 4 mg/d of micronized E2 resulted in favorable endometrium development in all patients in a mean time of 5 and 7 days, respectively. After P treatment, only 1 of 12 endometrial biopsies was in phase. In the treatment cycles, the overall clinical pregnancy rate (PR) was 42%. In those patients with a favorable endometrium in the E replacement phase, before addition of P, the PR was 62.5%. All of the pregnant patients but only 42.8% of the nonpregnant patients had a favorable endometrium on US before the addition of P. CONCLUSION: An endometrium that is favorable for implantation can result from the use of a simple fixed dose of E2, with higher doses achieving favorable endometrial development in shorter time. Vaginal sonography of endometrial development before P administration is more accurate than endometrial biopsy in predicting a successful donor egg cycle. Endometrial preparation in donor oocyte programs can be simplified by the use of vaginal US monitoring. PMID- 8486174 TI - The timing of placental competence in pregnancy after oocyte donation. AB - OBJECTIVE: To test the timing of placental support of pregnancy. DESIGN: Steroid levels in blood and urine were determined in pregnancy after ET into women with ovarian failure. SETTING: The study was carried out in a private IVF clinic and a university endocrine department. PATIENTS: Four patients with ovarian failure were treated by IVF using donor oocytes. INTERVENTIONS: Estrogen and P were given, up to the point of ET, to achieve the hormonal levels in the ranges for normal menstrual cycles. Pregnancy was supported in the first trimester by exogenous steroids. OUTCOME: The four pregnancies went to term, and each resulted in singleton livebirths. RESULTS: Increases in plasma P concentrations and in urinary pregnanediol excretion rates were indications for a placental contribution to the hormone pool. CONCLUSIONS: One hundred mg of P were probably a supraphysiological dose to support pregnancy 6 to 8 weeks after conception. The fetoplacental unit was competent from 10 to 12 weeks' gestation. PMID- 8486175 TI - The effect of gonadotropin-releasing hormone agonist on embryo quality and pregnancy rate following cryopreservation. AB - OBJECTIVE: To examine the effect of GnRH analogue (GnRH-a) on the quality of frozen-thawed embryos and the pregnancy rate (PR) resulting from transfer. DESIGN: A retrospective study of two groups of women undergoing transfers of frozen-thawed embryos. In group 1 ovulation induction with hMG was begun after hypophyseal desensitization with GnRH-a for 2 weeks. In group 2 ovulation was induced with hMG only. The freezing and thawing techniques were identical for both groups. SETTING: In vitro fertilization unit at a university hospital. PATIENTS: The study group (group 1) included 108 women who underwent 137 transfer cycles of frozen-thawed embryos, and the control group (group 2) included 44 women in 51 cycles of thawed ETs. INTERVENTIONS: Ovum pick-up and ET techniques were the same for both groups. Methods of embryo freezing and thawing were identical, as were the morphological criteria for grading the embryos. RESULTS: The morphology of embryos was similar in both groups, as was the number of embryos that had at least 50% intact blastomeres (83% +/- 23% and 78% +/- 30% for group 1 and group 2, respectively). The PR (16 of 137 [11.7%] and 6 of 51 [11.8%], respectively) as well as the abortion rate (30%) were similar for both groups. CONCLUSIONS: The use of GnRH-a does not affect the quality of embryos nor the pregnancy outcome. Because the yield of frozen embryos per ovum pick-up is higher in cycles stimulated by GnRH-a/hMG, the PR per pick-up cycle is thus anticipated to be higher. PMID- 8486176 TI - A multifactorial analysis of the pregnancy outcome in a successful embryo cryopreservation program. AB - OBJECTIVE: To determine which factor, or factors, may influence the success of an embryo-freezing program. DESIGN: Prospective. SETTING: An established, private IVF clinic. PATIENTS: This study comprises data from 185 consecutive thaw cycles (161 patients) that resulted in embryo replacement. The influence of the following factors, with regard to pregnancy outcome, was specifically addressed: embryo quality, day of the endogenous LH surge, number of thawed embryos replaced, length of time frozen, E2 level at the time of the hCG trigger in the stimulated cycle, and patient age at the time of freezing. RESULTS: An overall pregnancy rate (PR) of 27.6% per ET was achieved in this study. Regardless of the day of the LH surge, patients who had at least one good quality embryo (the "sponsoring embryo") conceived 35% of the time. Patients who lacked a sponsoring embryo frozen conceived 15% of the time. Patients who were 39 years of age or younger had a PR of 31% per transfer. None of the 22 patients who were 40 or older conceived. No other factor examined had any effect on pregnancy outcome. CONCLUSIONS: Good quality frozen/thawed embryos are a major factor in achieving a consistently high PR. Poorer quality embryos are capable of implantation but at a significantly reduced rate. Patient age was also found to be significant in predicting pregnancy. Neither the day of the LH surge, number of embryos transferred, length of time frozen, nor the E2 level appears to have any effect on the establishment of pregnancy. PMID- 8486177 TI - The hemizona assay: its role in identifying male factor infertility in assisted reproduction. AB - OBJECTIVES: To identify male factor infertility among a group of patients in an assisted reproductive program (phase 1) and to evaluate the hemizona assay (HZA) in the diagnosis and prognosis of such a program (phase 2). DESIGN: The IVF performance of normal gametes in the Tygerberg program were critically evaluated. Female patients were classified as pure tubal factor infertility, having a normal FSH:LH ratio on day 3 of the menstrual cycle. All participating women produced three or more preovulatory oocytes at retrieval and were inseminated with sperm considered normal by all present diagnostic criteria. The total and normal fertilization rate thresholds were defined in that group. Using those thresholds, couples tested for sperm binding in the HZA (n = 48) were used and divided into two groups according to their fertilization rates, namely group 1, low fertilization (< 55%) and group 2, normal fertilization (> 55%). SETTING: University-based tertiary care center. PATIENTS: Ninety-nine couples (589 oocytes) with pure tubal factor infertility and normal male factor were used in phase 1. Forty-eight couples with normal and abnormal male factors that had both HZA performed and IVF treatment were included in phase 2. RESULTS: Investigation of the performance of normal gametes in 99 couples (589 oocytes) revealed the total fertilization rate (total number of oocytes fertilized/total number of oocytes inseminated) was (mean +/- SD) 88.6% +/- 16.8% and the normal fertilization rate (total number of oocytes with normal fertilization/total number of oocytes inseminated) was 81.3% +/- 22%. The minimum total fertilization rate that can be considered normal in the Tygerberg program using mean--2 SD is therefore 55% and for normal fertilization rate is 37%. The group with low fertilization rate (< 55%) showed a mean hemizona index (HZI) significantly lower; nevertheless, the distribution overlapping indicates a low discriminating power of the HZA. A sensitivity of 75% and a specificity of 75% were found; the positive and negative predictive values were 81% and 68%, respectively. CONCLUSIONS: The results indicated the HZA and HZI contribute important information and can serve in conjunction with other semen characteristics as useful tools during the diagnosis of the male factor in assisted reproduction. PMID- 8486178 TI - Serum immunoactive inhibin levels in early pregnancy after in vitro fertilization and embryo transfer. AB - OBJECTIVE: To determine the maternal serum concentrations of inhibin, E2, P, and hCG in early pregnancies arising from IVF and ET or GIFT and to assess the value of these hormone measurements in determining outcome of pregnancy. DESIGN: Serum immunoactive inhibin, E2, P, and hCG levels were measured in the first trimester of pregnancies after IVF-ET and GIFT procedures. SETTING: In vitro fertilization and ET or GIFT was undertaken at Monash IVF, Melbourne, Victoria, Australia. PATIENTS: At least two blood samples were collected from 117 women between 4 and 11 weeks of gestation. MAIN OUTCOME MEASURES: The hormone concentrations in the IVF-ET and GIFT pregnancies were compared with those in pregnancies and related to outcome of pregnancy. RESULTS: Serum inhibin levels in singleton pregnancies were significantly higher than in comparable normal pregnancies. In contrast to normal conceptions in which inhibin concentrations rose to peak at 11 weeks, the levels found in IVF-ET and GIFT singleton pregnancies were high at 5 weeks' gestation and declined subsequently. In twin pregnancies, the inhibin levels were significantly greater than those in singleton pregnancies. In biochemical pregnancies diagnosed by increasing hCG concentrations in the absence of an embryonic sac, inhibin levels were significantly lower than those found in singleton pregnancy, as were E2, P, and hCG levels. In anembryonic pregnancies, diagnosed by the confirmation of an intrauterine gestation sac with no evidence of a fetal complex, inhibin concentrations were highest at week 4 and declined, being significantly lower at all stages of gestation. In ectopic pregnancy, serum inhibin levels were lower at all stages of gestation, whereas E2 concentrations were not lower until 6 weeks and P levels until week 5. Serum hCG levels were significantly lower at all stages of gestation. In women with spontaneous abortions, inhibin levels were lower than singleton pregnancies at 7 weeks. CONCLUSIONS: Serum inhibin concentrations are elevated in pregnancies arising from ovarian hyperstimulation in the first trimester when compared with those in normal pregnancy, probably as a result of the presence of multiple corpora lutea resulting from ovarian hyperstimulation. Serum inhibin, E2, P, and hCG are useful markers of abnormal pregnancy outcome. PMID- 8486179 TI - Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer. AB - OBJECTIVE: To determine if an increase in plasma P occurring before hCG administration might impair the outcome of IVF-ET. DESIGN: Five hundred eighty five IVF-ET cycles were prospectively studied for the occurrence of plasma P elevation before hCG administration. SETTING: Tertiary institution, IVF-ET program, Hopital A. Beclere. PATIENTS: Participating patients included IVF-ET candidates 23 to 42 years of age only, excluding the couples in whom a male factor was a primary or an accessory cause of infertility. MAIN OUTCOME MEASURES: To clarify the practical consequences on IVF-ET outcome of pre-hCG increases in plasma P, we studied 585 consecutive IVF-ET cycles. These were divided into two groups according to plasma P levels observed on the day of hCG administration; plasma P of 0.9 ng/mL (2.9 nmol/L) was taken as an arbitrary cutoff value. Group A included 485 IVF cycles in which plasma P was < or = 0.9 ng/mL (2.9 nmol/L); group B included the remaining 100 cycles in which plasma P was > 0.9 ng/mL (2.9 nmol/L). RESULTS: The number of mature oocytes retrieved, the oocyte cleavage rate, and the number of embryos obtained were similar in groups A and B. In contrast to this apparent similarity in oocyte quality, a decrease in pregnancy rate (PR) and a trend for a decrease in embryo implantation rate were observed in group B in comparison with group A. CONCLUSIONS: The similar fertilization and cleavage rates obtained in groups A and B suggest that pre-hCG elevation in plasma P does not lead to decreased oocyte quality. Yet the lower PR observed when plasma P rises prematurely suggests that the prolonged but discrete elevation in plasma P occurring in these cases might alter endometrium receptivity to embryo implantation. PMID- 8486180 TI - Serum antisperm antibodies in men with vas deferens obstruction caused by childhood inguinal herniorrhaphy. AB - OBJECTIVE: To study the incidence of serum antisperm antibodies in patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy. DESIGN: Retrospective. SETTING: Kansai Medical University and Kyoto University Hospital. PATIENTS: Thirteen patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy. MAIN OUTCOME MEASURES: Indirect immunobead test for serum antisperm antibodies. RESULTS: Of 13 patients, 7 (54%) and 2 (15%) tested positive for immunoglobulin (Ig)G and IgA class antisperm antibodies, respectively; all patients tested negative for IgM class antibodies. The incidence of antisperm antibodies was not different between the patients with possible epididymal obstruction and those without epididymal obstruction. CONCLUSIONS: A significant percentage of patients with vasal obstruction caused by infant inguinal herniorrhaphy have serum antisperm antibodies despite the absence of sperm granulomas. PMID- 8486181 TI - Detection of Chlamydia trachomatis in semen of artificial insemination donors by the polymerase chain reaction. AB - OBJECTIVE: To assess the feasibility of detecting Chlamydia trachomatis in cryopreserved donor semen by a specific, direct polymerase chain reaction (PCR). DESIGN: Cryopreserved donor semen was tested for the presence of C. trachomatis by a specific PCR, directly applied to semen without prior DNA purification. SETTING: Tertiary care fertility center in a teaching hospital and university based laboratory for molecular pathology. PARTICIPANTS: Cryopreserved semen from 30 donors was investigated. These semen samples had previously given negative results in cell culture for C. trachomatis. Two different ejaculates of each donor, cryopreserved with an interval of 2 years, were retrospectively analyzed. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The presence of C. trachomatis as demonstrated by PCR. RESULTS: In 3 of 30 donors C. trachomatis was detected in both ejaculates, whereas in 2 additional donors only one of the two samples tested positive. Additional samples from 2 positive donors, together with samples from 3 negative donors, were studied more extensively, to test the reproducibility and reliability of PCR results. All ejaculates of the donors, previously positive for C. trachomatis by PCR, indeed appeared to be positive, whereas the samples of the negative donors remained negative. CONCLUSIONS: The direct PCR is a reliable, sensitive, and valuable method for detection of C. trachomatis in semen. The incidence of contamination of donor semen with C. trachomatis in the donor population in this study stresses the need for rigorous screening of donor semen before artificial insemination, preferably using a sensitive method such as the PCR. PMID- 8486182 TI - The effects of Vero (green monkey kidney) cell coculture on the motility patterns of cryopreserved human spermatozoa. AB - OBJECTIVE: To determine the effects of Vero (a primate, urogenital epithelium derived cell line) cell monolayer coculture on cryopreserved human sperm function in vitro. DESIGN: Prospective, controlled investigation in which cryopreserved semen specimens were thawed, processed, and then simultaneously exposed to control media (Dulbecco's modified Eagle's medium with either 10% heat inactivated fetal bovine serum [FBS] or 10% heat-inactivated pooled human sera [PHS]) or the same media with the addition of confluent Vero cell monolayers. A second series of investigations was also performed to study the effect of Vero cell conditioned media (CM). SETTING: In vitro fertilization/andrology service of tertiary center. PATIENTS: Donors with normal semen parameters. INTERVENTIONS: Coculture of human spermatozoa with Vero cell monolayers or Vero cell CM. MAIN OUTCOME MEASURES: General and hyperactivated (HA) motility patterns, multifactor, repeated measures ANOVA. RESULTS: General sperm motility parameters, including percentage motility, mean velocity, and mean amplitude of lateral head displacement were significantly greater than controls in the Vero cell monolayer FBS group at 6 hours and in both the Vero cell monolayer-FBS and Vero cell monolayer-PHS groups by 24 hours. Hyperactivated motility was increased after 3 hours in the Vero cell monolayer-FBS coculture group. A significant decrease in the total sperm concentration over the time course of the study in the Vero cell monolayer, but not the control or Vero CM groups, was also noted. Vero CM did not exert significant effects on any sperm motility parameter, in spite of a sample size sufficient to detect relevant increases with a power of 0.80. CONCLUSIONS: Vero cell monolayers have a positive influence on cryopreserved sperm function as assessed by general and HA motility patterns. Epithelial cell to spermatozoon contact seems to be important in this process. PMID- 8486183 TI - The effect of the motility stimulants, caffeine, pentoxifylline, and 2 deoxyadenosine on hyperactivation of cryopreserved human sperm. AB - OBJECTIVE: To determine if the motility stimulants, caffeine (7 mM), pentoxifylline (3 mM), 2-deoxyadenosine (3 mM), and a combination of the three would induce hyperactivated (HA) motility. DESIGN: Controlled laboratory study of stimulants using cryopreserved semen from 10 donors at three time points. SETTING: The study was performed in the Andrology Laboratory at Prince Henry's Institute of Medical Research Clayton, Victoria, Australia. INTERVENTIONS: Stimulants in doses maximally effective for stimulation of motility were incubated with suspensions of previously cryopreserved sperm. MAIN OUTCOME MEASURES: Motility characteristics (curvilinear velocity [VCL], linearity [LIN], and maximum amplitude of lateral head displacement [ALHmax]) were derived using the single cell track facility of the CellSoft computer-automated semen analyzer (Cryo Resources Ltd., Montgomery, NY). Videotapes were visually inspected, and 125 sperm cell trajectories exhibiting characteristic HA behavior were identified. The HA motility thresholds (5th or 95th centiles) were as follows: VCL > 74 microns/s, LIN < 74%, and ALHmax > 4.7 microns. Cells with motility characteristics outside these limits were regarded as HA. The significance of the effect of the stimulants on the proportion of sperm exhibiting HA was examined by Poisson regression analysis. RESULTS: Sperm washing (removal of the cells from the cryoprotectant) and swim-up caused significant changes in the VCL and straight line velocity and a twofold (5.6% to 11.9%) increase in the proportion of HA cells. In the presence of motility stimulants, the proportion of HA cells was significantly increased threefold (11.9% to 32.5%) above that seen in the control washed sperm. Hyperactivated motility declined after 1 to 2 hours, but 2 deoxyadenosine demonstrated a prolonged effect. CONCLUSION: These motility stimulants that affect adenosine 3':5' monophosphate in human sperm stimulate cyclic hyperactivation. PMID- 8486184 TI - Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal male range. AB - OBJECTIVE: To examine the relationship between serum T levels and sexual function when T levels are varied in the normal male range by pharmacological means. Two groups of healthy men were treated with a depot form of GnRH agonist leuprolide acetate (Lupron depot; TAP Pharmaceuticals, Chicago, IL) on days 1 and 31 to suppress endogenous T production and either 4 (n = 6) or 8 (n = 5) mg/d T replacement by a sustained release, long-acting T microcapsule formulation on day 1. OUTCOME MEASURES: Sexual function was evaluated by daily logs of sexual activity and electroencephalogram-coupled nocturnal penile tumescence recording before and after 9 weeks of treatment. RESULTS: Serum T levels in 4 and 8 mg/d groups were at low and high ends of the normal male range, respectively (10.5 +/- 1.7 versus 26.5 +/- 3.4 nmol/L). The number and duration of rapid eye movement (REM) periods, latency to REM sleep, erections/REM period, magnitude, and duration of tumescence were not significantly different between the 4 and 8 mg groups. Sexual logs also did not show significant differences in overall scores or in subcategories of intensity of sexual feelings (libido) and sexual activity between the two doses. CONCLUSIONS: These data indicate that erectile function and sexual activity and feelings are restored by relatively low T levels. These data may help explain why some partially hypogonadal men continue to have normal sexual function and the absence of good correlation between serum T levels in the normal range and sexual function. PMID- 8486185 TI - Gonadotropin responsiveness to ultralow-dose leuprolide acetate administration in baboons. AB - OBJECTIVE: To evaluate the gonadotropin response to ultralow doses of a GnRH agonist, leuprolide acetate (LA). DESIGN: Prospective and cross-controlled. SETTING: Primate research center. SUBJECTS: Four reproductive age cycling baboons (Papio cyanocephalus). INTERVENTIONS: Three different doses of LA were given intravenously to each animal followed by serial sampling. MAIN OUTCOME MEASURES: Response patterns of circulating serum gonadotropin levels. RESULTS: All four animals responded to each of the three doses of LA in a dose-dependent fashion. Levels of LH and FSH peaked at 49.5 +/- 2.6 mIU/mL and 72.5 +/- 3.4 mIU/mL, respectively, for the highest dose studied (0.17 microgram/kg). Levels of LH peaked earlier but were lower than the FSH peak levels. CONCLUSIONS: Supraphysiological levels of gonadotropins are attained after the administration of ultralow doses of LA. The level of the response is dose-dependent and is in the range that is required to attain controlled ovarian hyperstimulation. PMID- 8486186 TI - Ultrasonically guided follicular aspiration during a pregnancy with massive ovarian cysts following ovulation induction by gonadotropins. AB - In this report, the treatment by follicular aspiration was evaluated in a pregnant patient with severe ovarian cysts subsequent to ovulation induction with CC and gonadotropins. The patient had dramatic and immediate improvement of the symptoms and general condition as well as a significant shorter hospital stay. The procedure was, under meticulous US guidance, safe and effective, providing additional improvement or increased therapeutic confidence in the severe complications after ovulation induction, as an assisted option during pregnancy. PMID- 8486187 TI - Use of particle filters for increased practicability in sperm processing: application to the indirect immunobead test. AB - The use of sterile particle filters is described for the washing and incubation of living sperm before the indirect IBT. The filters greatly simplify the technique, shorten its duration, and remove all centrifugation steps that have potentially detrimental effects on the sperm. The same filters have a variety of applications and can be used whenever sperm have to be washed or incubated before biochemical tests including acrosome binding studies and flow cytometry. PMID- 8486188 TI - Controversy about immunotherapy. PMID- 8486189 TI - Empty follicle syndrome in perimenopausal patients. PMID- 8486190 TI - Detection of human immunodeficiency virus in blood or semen by polymerase chain reaction--reliable? PMID- 8486191 TI - Detection of human immunodeficiency virus in blood or semen by polymerase chain reaction--reliable. PMID- 8486192 TI - Placebo effect--how powerful? PMID- 8486193 TI - Embryo biopsy strategies for preimplantation diagnosis. AB - OBJECTIVE: To analyze different biopsy methods, embryo stages, and cellular masses that can be removed for preimplantation diagnosis of genetic diseases to find optimal biopsy conditions compatible with the subsequent development of the conceptus, the acquisition of intact viable blastomeres, and the reliability of the genetic analysis. DATA IDENTIFICATION: The most important published studies have been identified through a computerized bibliographical search (MEDLINE; Dialog, Palo Alto, CA). STUDY SELECTION: Studies reporting different embryo biopsy methods practiced at different stages have been selected. RESULTS: The analysis carried out in the current review shows, at the present time, the following: [1] the displacement and push methods may be more suitable than the stitch and pull and aspiration (puncturing the zona pellucida) approaches at cleavages stages; [2] the aspiration and stitch and pull procedures may assure higher success rates than the herniation procedure at the blastocyst stage; [3] the mechanical division method and the use of acid Tyrode's solution would not be advisable before the eight-cell stage; [4] human embryos at the two-cell and blastocyst stages may not be suitable for preimplantation diagnosis because of an excessive reduction of cellular mass at the two-cell stage and a low or zero pregnancy rate after transfer at the blastocyst stage; and [5] biopsy of a quarter of the embryonic cellular mass on day 2 after insemination may increase biochemical pregnancies if the cleavage rate is not preserved. CONCLUSIONS: At the present time, biopsy of a quarter of the embryo on day 3 after insemination may be the most feasible approach for preimplantation diagnosis. PMID- 8486194 TI - Computer-aided sperm analysis: technology at a crossroads. PMID- 8486195 TI - Assisted reproductive technology in the United States and Canada: 1991 results from the Society for Assisted Reproductive Technology generated from the American Fertility Society Registry. AB - OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive technology (ART) initiated in the United States in 1991. DESIGN: Data were collected on an annual summary form and submitted to the Society for Assisted Reproductive Technology generated from The American Fertility Society central registry. PARTICIPANTS: Two hundred fifteen programs submitted data on procedures performed in 1991. Data were collected in October of 1992 so that outcome of all pregnancies established would be known. MAIN OUTCOME MEASURES: The outcomes measured included clinical pregnancy, ectopic pregnancy, abortion, stillbirth, delivery, and congenital abnormality. RESULTS: In 1991, programs reported initiation of 33,001 cycles of ART treatment, excluding frozen embryo and donor oocyte cycles. Of these, 24,671 cycles initiated were IVF with 15.2% deliveries per retrieval, 5,452 were cycles of GIFT with 26.6% deliveries per retrieval, and 2,104 were cycles of zygote intrafallopian transfer with 19.7% deliveries per retrieval, and 714 were combination cycles, combining IVF and one of the tubal transfer techniques, resulting in 19.3% deliveries per retrieval. In addition to these cycles initiated in 1991, 4,838 frozen embryo procedures were reported, either as separate procedures or in combination with another ART procedure with 11.1% deliveries per procedure, and 1,107 donor oocyte or surrogacy cycles were initiated with an overall success of 25.6% deliveries per retrieval. From all of these procedures, a total of 5,699 deliveries were reported. CONCLUSIONS: In 1991, there were more programs offering more treatment cycles of ART. Average success rates for most ART procedures exhibited a small increase compared with previously reported summaries. PMID- 8486196 TI - A quantitative overview of controlled trials in endometriosis-associated infertility. AB - OBJECTIVE: To undertake quantitative overviews of the following commonly used treatments for endometriosis-associated infertility: ovulation suppression, laparoscopic ablation, and conservative laparotomy. DESIGN: A protocol was prospectively defined detailing the research question, mode of study identification, inclusion and exclusion, data extraction, and pooling methods. Studies were assessed for relevance and validity by independent reviewers and their findings compared. Data were extracted in a similar fashion. PATIENTS: Women with visually diagnosed endometriosis, complaining of infertility. MAIN OUTCOME MEASURE: Pregnancy as defined by positive pregnancy test. RESULTS: Twenty five relevant randomized controlled trials and cohort studies were identified with a total of 37 treatment comparisons. The common odds ratio (OR) from seven studies comparing ovulation suppression (danazol, medroxyprogesterone acetate [MPA], or gestrinone) versus placebo or no treatment was 0.85, suggesting no treatment benefit. The common OR for pregnancy after ovulation suppression (MPA, gestrinone, or GnRH agonist) versus danazol was also nonsignificant: 1.07. Although pooled data from trials of laparoscopic surgery suggested a treatment benefit, significant heterogeneity between studies undermines this conclusion. Laparoscopic data were similar to those from conservative laparotomy studies. Studies assessing conservative surgery plus danazol versus danazol alone showed no significant benefit from this adjunct. CONCLUSION: Ovulation suppression is an ineffective treatment for endometriosis-associated infertility. Well-designed trials of laparoscopic ablation deserve a high priority. PMID- 8486197 TI - Response to intermittent RU486 in women. AB - OBJECTIVE: To determine the effects of intermittent administration of the antiprogestin RU486 on ovarian function. DESIGN: Three different regimens of RU486 were tested. PARTICIPANTS: Nine healthy regularly menstruating volunteers protected by an intrauterine device or surgical sterilization. INTERVENTIONS: Two groups of three women each received 10 mg or 50 mg RU486 at weekly intervals for 5 weeks. Another three women received 50 mg RU486 for 3 consecutive days at 10 day intervals for 80 days. MAIN OUTCOME MEASURES: Serum E2, P and RU486 levels. Ovarian ultrasound (US) and serum LH and FSH in select subjects. RESULTS: The predominant effect was partial inhibition of E2 secretion and suppressed P levels. During a total aggregate of 16 treatment months, there were seven episodes of elevated P levels; however, US did not always indicate the occurrence of normal ovulation. CONCLUSION: Intermittent RU486 administration can interfere with normal follicular development and function, but its clinical application may require a more effective dose and/or timing of administration. PMID- 8486198 TI - A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction. AB - OBJECTIVE: To assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy. DESIGN: A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued. RESULTS: The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects. CONCLUSION: Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy. PMID- 8486199 TI - Long-acting injectable bromocriptine (Parlodel LAR) in the chronic treatment of prolactin-secreting macroadenomas. AB - OBJECTIVE: To evaluate the efficacy and tolerability of Parlodel LAR (Sandoz, Basel, Switzerland), a long-acting injectable bromocriptine, in PRL-secreting macroadenomas. DESIGN: Eleven patients with macroprolactinomas were studied in an academic environment in an open and prospective protocol. Ten patients were followed for 6 months and 8 for 1 year. Fifty to 200 mg IM of Parlodel LAR were administered every 28 days. RESULTS: At the end of the 1st month, 64% of the patients had PRL suppression of > 75% of baseline values. After 1 year, 88% of the cases had PRL suppression of > 90%. Persistent PRL normalization was seen in three cases. Tumor shrinkage was seen in 64% of the patients on day 5, in 73% on day 28, and in 90% after 6 months of treatment. Early visual field improvement was seen in 83% of the cases. All patients had improvement of clinical symptoms. CONCLUSION: Parlodel LAR is well tolerated and very effective in the long-term treatment of patients with PRL-secreting macroadenomas. PMID- 8486200 TI - High-dose, short-term glucocorticoids for the treatment of infertility resulting from premature ovarian failure. AB - OBJECTIVE: To evaluate prospectively the effects of high-dose, short-term treatment with a glucocorticoid in an attempt to normalize ovarian failure and induce pregnancy in women presenting with infertility. DESIGN: Uncontrolled, nonrandomized prospective study. SETTING: Two university-based reproductive endocrinology clinics. PATIENTS: Eleven consecutive women with premature ovarian failure (POF) who were desirous of pregnancy. INTERVENTIONS: Prednisone 25 mg four times per day for 2 weeks. MAIN OUTCOME MEASURES: Two women demonstrated normalization of their serum gonadotropins, an increase of serum E2, and ultrasonographic visualization of follicular growth, with both conceiving. The other nine demonstrated no biochemical or clinical response. CONCLUSIONS: Premature ovarian failure may not be an irreversible process and may either spontaneously resolve or may respond to therapeutic modalities such as high-dose glucocorticoids in selected patients. In this uncontrolled study, the results were best with women with concomitant autoimmune thyroid disease and POF of < 2 years' duration. PMID- 8486201 TI - Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes. AB - OBJECTIVE: To determine the relative influences of induction of withdrawal bleedings secretory transformation, and reduction of mitosis in glands on prevention of endometrial hyperplasia during long-term hormonal replacement therapy. DESIGN: Observational expanded clinical case report. SETTING: Reproductive Endocrine Department of Hospital Necker, Paris, France, and Pathology Department of Women's Hospital, Los Angeles County and University of Southern California Medical Center, Los Angeles, California. PATIENTS: Postmenopausal women seeking treatment for symptomatic menopause. INTERVENTIONS: Endometrial biopsy and/or ambulatory hysteroscopy. MAIN OUTCOME MEASURE: Endometrial histology including progestational maturation patterns and glandular epithelial mitosis rates. Macroscopic endometrial appearance. RESULTS: The use of larger doses of E2 and P induced more marked secretory changes and more frequent withdrawal bleeding than the lower doses. There was no evidence of endometrial hyperplasia after 5 years of E2/P replacement therapy independently of bleeding pattern or progestational maturation. Consistent reduction of mitosis rates in glandular epithelium was found after 9 or more days of P administration in each cycle. CONCLUSIONS: Control of endometrial growth is mainly related to control of mitosis in glands by a relatively low doses of P. Induction of withdrawal bleeding and endometrial secretory transformation, which require larger doses of Progesterone, do not provide additional benefit for prevention of hyperplasia. Induction of amenorrhea with a relatively low dose of P may be offered to women seeking hormone replacement therapy with similar levels of safety. PMID- 8486202 TI - Sonographic assessment of ovarian and endometrial changes during long-term Norplant use and their correlation with hormonal levels. AB - OBJECTIVE: To study the probability of ovulation and subclinical abortion during long-term use of Norplant and to assess the concomitant endometrial development. DESIGN: This was a prospective nonrandomized comparative study. The ovaries and endometrium were assessed daily by ultrasonography during 59 menstrual cycles in 50 women who were using Norplant for > 1 year. Serum concentrations of E2, P, FSH, LH, pregnancy specific beta 1 glycoprotein (Sp1), and hCG were also daily measured. The findings were compared with those in 35 ovulatory cycles in normal fertile women not using contraception. SETTING: Clients of the Family Planning Clinic of Assiut University Hospital (Norplant users) and the hospital women staff (controls). RESULTS: Sonographic and hormonal evidence of ovulation were observed in one third of Norplant users; two of them resulted in conception. However, the majority of these ovulatory cycles showed low midcycle peaks of E2, FSH, and LH and evidence of luteal phase defect (LPD). Excessive follicular enlargement was observed in 46% of the cycles. Norplant users had significantly thinner endometrium that did not exhibit the normal phasic changes in sonographic texture. Apart from conceptive cycles, no rise in Sp1 or hCG was observed. CONCLUSIONS: Norplant acts mainly by inhibiting ovulation, but when this occurs, it is associated with LPD and subnormal endometrial development. Subclinical abortion does not contribute to the contraceptive effect. PMID- 8486203 TI - [Gonadotrophin-releasing hormone agonist in the treatment of hypogonadotrophic secondary amenorrhoea]. AB - In an attempt to induce ovulation in Clomiphene resistant secondary amenorrhoea patients, the gonadotrophin-releasing hormone agonist (Buserelin) (600-900 micrograms/day) was administered in 13 cases aged 18 to 24 years for one week from day 5 of the menstrual cycle. Serum levels of luteinizing hormone increased in all patients, and estradiol levels increased in 10 of 13 patients in response to Buserelin. However, ovulation was observed in 6 cases, and the response to Clomiphene was recovered in all of these 6 cases in their subsequent menstrual cycles. These results imply the existence of a subgroup who respond to Buserelin in Clomiphene resistant secondary amenorrhoea patients and a possible new approach for the treatment of secondary amenorrhoea. PMID- 8486204 TI - [Metabolism, structure and biological activity of sex steroids]. AB - Recently, the action of steroid hormones are interpreted as the results from the interaction with its proper receptors. However, every steroid hormones and steroid drugs have many biological effects, and if one steroid receptor is enough to result in these multiple effects or not is not well known. On the other hand, our experimental results showed that some steroid drugs are metabolized, in vivo, to form several biologically active compounds. Norethindrone, a representative progestational compound, has also some estrogenic and androgenic effects. It was demonstrated, in our laboratory, that the compound was converted, in vivo, to several androgens and to estrogen, ethynyl estradiol. Since it was demonstrated later that ethynyl estradiol but not norethindrone showed estrogenic activity in vitro, it can be concluded that the estrogenic activity of norethindrone was derived from the metabolite of norethindrone, ethynyl estradiol. Although the chemical structure of norethindrone is far different from that of progesterone, it was demonstrated that the progestational effect of norethindrone was derived from the interaction of norethindrone with progesterone receptor. The binding site of norethindrone with the receptor is identical with that of progesterone. Some steroid drugs, such as lynestrenol are inactive, per se, and the conversion of the compound into norethindrone in liver tissue well explained the progestational activity of the compound. In such cases, the studies on the interaction of original compound with receptor in target tissues will give us poor information on the mechanism of steroid action. Some progestational compounds such as medroxyprogesterone acetate has anticancer effect, but norethindrone and the related compounds have no such an effect. This indicates that the receptor for anticancer effect is different from the receptor for common progestational effect. This was confirmed by many ways and the receptor for anticancer effect was partially characterized. Although dydrogesterone is a potent progestational agent and the endometrial response to this compound is almost identical with that to progesterone, it results in neither the elevation of basal body temperature nor an inhibition of ovulation, which are commonly observed with other progestogens. This also raises a doubt on the identity of progesterone receptors in peripheral and central tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8486205 TI - [A case of bilateral aldosterone-producing adrenal adenomas]. AB - A 43-year-old female was admitted to our hospital for high blood pressure control. She showed hypokalemia with increased urinary potassium excretion, high plasma aldosterone concentration (33.9ng/dl, normal range; 2-12ng/dl) and reduced plasma renin activity (trace, normal range; 0.83-5ng/ml/hr). Bilateral adrenal tumors were revealed by abdominal computed tomography, and left adrenalectomy and right partial adrenalectomy were performed. Cytochromes p-450 and other enzymes involved in aldosterone synthesis were found predominantly in the tumor portions but not in the zona glomerulosa of the attached adrenals, which histopathologically showed paradoxical hyperplasia. This was a rare case of bilateral aldosterone-producing adrenal adenomas, which we could differentiate from idiopathic hyperaldosteronism by employing immunohistochemical analysis of steroidogenic enzymes. PMID- 8486206 TI - Angiotensin II receptor subtypes: characterization, signalling mechanisms, and possible physiological implications. AB - Thanks to the recent discovery of angiotensin II (ANG II) receptor subtypes linked to different signalling pathways, research in the different areas related to this peptide has regained a strong interest. In the following review, we first describe the biochemistry and actions of angiotensin peptides formed both in the circulation and locally at the tissue and organ level. Evidence for the existence and distribution of ANG II receptor subtypes in mammalian as well as in nonmammalian species and lower organisms is presented. The changes in receptor subtype expression during development and disease are described. The signal transduction mechanisms and biological actions of ANG II mediated by the recently cloned AT1 receptor are reviewed and the recent data concerning the signalling pathways linked to the AT2 receptor are discussed. Finally, based upon their molecular pharmacology, we present evidence and also speculate upon the physiological function of the ANG II receptor subtypes. PMID- 8486207 TI - Involvement of the area postrema in the regulation of sympathetic outflow to the cardiovascular system. AB - The circumventricular organs of the brain have been implicated in the central regulation of the cardiovascular system. The area postrema, which is the only circumventricular organ in the hindbrain, has received less attention than the others, but recent studies suggest that it may play an important role in the regulation of the cardiovascular system. Studies in rats and rabbits indicate that angiotensin II (Ang II)-dependent hypertension is abolished by lesioning of the area postrema. Additional studies indicate that the hypertension associated with Ang II involves a resetting of the arterial baroreflex to a higher pressure. This upward resetting requires an interaction of neurons in the area postrema with barosensitive neurons terminating in the medial nucleus tractus solitarius (mNTS). Another peptide, arginine vasopressin (AVP), has been shown to enhance the sympathoinhibitory influence of the arterial baroreflex via an action at the area postrema. Studies in rabbits suggest that the sympathoinhibitory response is due to resetting of the baroreflex to a lower pressure. Electrophysiological studies, using an in vitro brain slice preparation, have shown that activation of area postrema neurons projecting to the mNTS alters the responsiveness of mNTS neurons to afferent inputs. It is postulated that alpha-adrenergic mechanisms are involved in these interactions. PMID- 8486208 TI - Esophageal cancer associated with multiple cancerous lesions: clinicopathologic comparisons between multiple primary and intramural metastatic lesions. AB - Detailed histopathological examination of serial blocks and subserial sections of the entire resected esophagus in 111 patients who underwent esophagectomy for esophageal squamous cell carcinoma revealed 38 associated cancerous lesions apart from the main tumors, in 33 patients (29.7%). These associated lesions were divided into multiple primary lesions (MPLs; 27 lesions in 23 patients) and intramural metastatic lesions (IMLs; 11 lesions in 10 patients). Thirteen and fourteen MPLs were distributed on the proximal and distal sides, respectively, of the main tumor with the same mean distance of 2.6 cm. Three and 8 IMLs were located on the proximal and distal sides, respectively, with mean distances of 3.4 cm and 4.6 cm. With respect to the histological depth of cancer invasion, MPLs were all confined within the submucosal layer (superficial cancer) while IMLs varied from the submucosa to the adventitia. Histological findings indicate that MPLs may be associated with a possible increased multicentric carcinogenic potential in the non-cancerous epithelium of the esophagus of patients who have had an antecedent esophageal cancer, and that IMLs are developed by intramural lymphatic spread from the primary esophageal cancer. These results emphasize the need for careful attention to the choice of margins during the surgical resection of the esophagus. PMID- 8486209 TI - Endoscopic evaluation of the depth of invasion of the depressed type early gastric cancer and apparently early advanced cancer in cases of a peptic ulcer within the cancer lesion. AB - Depressed-type early and apparently early advanced cancers were divided into two groups according to whether or not an associated peptic ulcer was present within the cancer lesion, and the accuracy of preoperative endoscopic diagnosis was reviewed. As a result it was found that evaluation of depth of invasion was more difficult in the ulcer [UL(+)] group than in the group without an ulcer [UL(-)]. In the UL(+) group it was difficult to identify endoscopic findings which indicate depth of invasion at the tip of the folds, the volume of cancer invasion of the deeper layers was small, and there many cases of invasion of deeper layers in a portion of the margins of the peptic ulcers. PMID- 8486210 TI - Small bowel transplantation in rats: endoscopic and histological evaluation of graft rejection. AB - Heterotopic small bowel transplantation was performed using the cuff technique in DA(RT1a) to PVG(RT1c) rat fully allogeneic combination. In this model, the rejection course of the grafted intestine was evaluated endoscopically via double stomata and was classified into four stages. Early changes appeared on postoperative day 3. Stage I: The mucosa of the grafted intestine showed patchy paleness and loss of the capillary fine network patterns, accompanied by microerosions. Closer examination revealed irregularity of the epithelial height and arrangement. Stage II: The damage spread progressively over the entire mucosa on day 4-5. Stage III: On day 6-7, the necrotic epithelium became detached, showing multiple ulcers which provoked hemorrhagic enteritis. Stage IV: Graft rejection was completed with total necrosis and white scar tissue formation by day 10-14. These endoscopic findings of the mucosa of the grafted intestine corresponded closely to the time course of pathological examinations. We conclude that endoscopic examination of grafted intestine may be an effective diagnostic tool to detect the rejection phenomenon at an early stage, as well as a simple tool to use for postoperative follow-up in combination with pathological examination. PMID- 8486211 TI - The effect and mechanism of the prokinetic action of cisapride on gastrointestinal smooth muscle. AB - Cisapride is a new prokinetic agent which can facilitate or restore motility throughout the entire gastrointestinal tract. Although facilitation of acetylcholine release has been suggested, the mechanism of action of cisapride is not clear. To investigate the effect and mechanism of action of cisapride, we used isolated muscle strips (with mucosa and submucosa removed) of guinea pig antrum, ileum and colon to study: (1) the dose response to cisapride, (2) the effect of antagonists (atropine and tetrodotoxin) on the stimulatory effect of cisapride. Besides these studies, we also used 3H-acetylcholine release method to investigate the acetylcholine release effect of cisapride. Cisapride elicited a dose-related enhancement of baseline activity (motility index) on the antrum and contraction on the ileum and colon at the dose of 4, 40 and 400 nM. At higher doses (4 microM) cisapride caused inhibition. This bell-shaped dose response curve suggested that cisapride might be autoinhibitory or that the receptors of cisapride might consist of high affinity stimulatory and low affinity inhibitory sites. The stimulatory responses elicited by cisapride (400 nM) were not significantly inhibited by atropine and tetrodotoxin in the antrum, ileum and colon. This suggested that cisapride might act directly on the smooth muscle. Cisapride (400 nM) evoked a rather small increase of 3H-acetylcholine release on the antrum, ileum and colon. Because the percentage of increase was small and we had demonstrated that the stimulatory effects of cisapride were not blocked by atropine and tetrodotoxin, the acetylcholine release effect of cisapride was considered unimportant. PMID- 8486212 TI - Studies on changes of colonic mucosal PGE2 levels and tissue localization in experimental colitis. AB - Experimental ulcerative colitis was produced in rats and the changes of PGE2 levels in the colonic mucosa and the tissue localization of PGE2 were studied immunohistochemically during the process of onset and healing of the experimental lesions. Compared with that in controls, PGE2 levels in colonic mucosa were not significantly higher in the early stage of inflammation, but rose gradually with exacerbation of inflammation, and after reaching peak values at the peak stage of development of colitis, decreased as signs of inflammation receded. Immunohistochemical study of the normal rat colon showed that PGE2 was uniformly positive in the muscularis mucosa and in the tunica propria muscularis adjacent to the submucosal layer. Furthermore, as the inflammation progressed infiltrating inflammatory cells also became positive, especially macrophages. These changes decreased along with regeneration of the epithelium and resolution of the inflammation. Glandular epithelial cells did not show positivity. These results made it clear that the PGE2 level in colonic mucosa is an useful index of the activity of colitis and that changes in PGE2 levels are associated with infiltration by inflammatory cells, principally macrophages, of the interstitium. The results also suggested the possibility that the muscularis mucosa plays a role in the colonic mucosal protective system. PMID- 8486213 TI - Intermittent bursts of motor activity in the human rectum and absence of propagation. AB - Manometric recordings from multiple sites were performed to determine the propagating properties of intermittent bursts of motor activity in the human rectum. Pressure changes were recorded simultaneously at 12.5 cm, 10 cm and 7.5 cm from the anal verge in nine healthy subjects for a total recording time of 32 hours, each study lasting 2.7-4.8 hours. The burst motor activity was identified on 19 occasions in 7 of 9 subjects at 12.5 cm; 26 occasions in all subjects at 10 cm; and 11 occasions in 3 of 9 subjects at 7.5 cm. In most cases, the burst motor activity was observed at a single recording site while other recording sites were quiescent. It did not appear to migrate in either an oral or aboral direction. The burst motor activity contained in part runs of pressure waves with a regular frequency: at 12.5 and 10 cm of the recording site, runs of regular pressure waves were dominated by a frequency of 2.5-5 cycle per minute, whereas those at 7.5 cm occurred with a higher frequency and a lower amplitude as compared with the more proximal recording sites. No evidence of propagation of each pressure wave was seen even when the burst occurred simultaneously at more than two recording sites. These results suggest that the intermittent bursts of rectal motor activity occur locally and do not propagate in either on oral or aboral direction. They appear dissimilar to the interdigestive migrating motor complex observed in the more proximal part of the gut. PMID- 8486214 TI - A new surgical procedure consisting of ligation of the common hepatic artery and auto-transplantation of hepatocytes into the spleen for end stage liver cirrhosis accompanied by ascites. AB - The authors developed a new surgical procedure for end stage liver cirrhosis associated with ascites. This procedure consists of ligation of the common hepatic artery and hepatocyte inoculation into the spleen (method A) and in this study is compared with common hepatic artery ligation alone (method B). Six of the eleven dogs operated by method A survived for six months or more with a significant (P < 0.01) difference in the three month survival in comparison with method B. In the hemodynamic study of both methods, the portal vein pressure and portal resistance decreased as a result of operation, but in method B, they returned to preoperative levels and in method A the low levels persisted for more than one year. In our method, liver function improved remarkably after three months. The hepaplastin and the cholinesterase levels increased after three months in method A with a significant difference (P < 0.01) in comparison with method B. The labeling index (L.I.) of intrasplenic hepatocytes also increased three months later. We emphasize that our method is an ideal procedure not only to improve portal haemodynamics but also to improve liver function, in end stage cirrhosis. PMID- 8486216 TI - Hyperbaric oxygen therapy in the treatment of refractory peripancreatic abscess associated with severe acute pancreatitis. AB - Five patients with peripancreatic abscesses associated with severe acute pancreatitis were treated by hyperbaric oxygen therapy (HBO). In 3 patients, the course after surgical mobilization of the pancreas and drainage of the pancreas bed was complicated by peripancreatic abscesses. HBO was conducted under a pressure of 2.8 atmospheres for two hours daily. Four of the 5 patients showed a progressive improvement in their condition. In one patient who failed to respond despite seven sessions of HBO, Pseudomonas aeruginosa was isolated from the discharge, and resection of necrotic tissue and drainage were performed. The main effects of HBO were the alleviation of high spiking fever, the improvement of white blood cell count and serum amylase levels, and the reduction of the abscess size. We recognized HBO to be a successful treatment for peripancreatic abscess associated with severe acute pancreatitis and better results were obtained than in cases that did not receive HBO. PMID- 8486215 TI - Effect of a somatostatin analogue (SMS 201-995) on hemodynamics and glucagon secretion in cirrhotic rats. AB - The effects of somatostatin analogue, SMS 201-995, on systemic and splanchnic hemodynamics and glucagon secretion were investigated in control and cirrhotic rats induced by thioacetamide administration. Hemodynamics were measured using the radioactive microsphere method. Immunoreactive glucagon (IRG) was determined in the portal vein and femoral artery and the splanchnic output (OP) of IRG was calculated. In control rats, SMS 201-995 induced a decrease of 5.6% in portal venous inflow and a 25.8% decrease in OP of IRG. In cirrhotic rats, SMS 201-995 produced a 14% decrease in portal pressure, a 13.6% decrease in portal venous inflow, and a 57.8% decrease in OP of IRG. In systemic hemodynamics no significant changes were noted following SMS 201-995 administration in the control or cirrhotic rats. The ratio of cirrhotic rats to the controls in the rate of decrease in portal venous inflow was similar to that in the percentage of decrease in OP of IRG. We conclude that SMS 201-995 is useful for the treatment of portal hypertension because of its effect of reducing portal pressure with mild changes in systemic hemodynamics. We suspect that the decrease in portal venous inflow by SMS 201-995 is mainly due to a reduction in the release of glucagon, a vasodilatory gastrointestinal hormone. PMID- 8486218 TI - Kimura's disease (angiolymphoid hyperplasia with eosinophilia) associated with ulcerative colitis. AB - We treated a 35-year-old Japanese woman who had Kimura's disease associated with ulcerative colitis. Kimura's disease is an uncommon chronic inflammatory disease considered to be of allergic origin based on the presence of eosinophilia and IgE hyperimmunoglobulinemia, and may be a manifestation of a systemic immunologic disturbance. Some immunological complications such as nephrotic syndrome have been reported in association with Kimura's disease, but the present case is the first associated with ulcerative colitis. PMID- 8486217 TI - Relationship between biliary excretion of bilirubin and glutathione disulfide. AB - The effects of two glutathione-oxidizing agents, t-butyl hydroperoxide and diamide, on biliary excretion of bilirubin and glutathione disulfide were investigated in anesthetized male Sprague-Dawley rats. Bilirubin (unconjugated) was infused at a constant rate of 100 nmol/kg/min through the jugular vein. When biliary excretion of bilirubin was stabilized, either of the glutathione oxidizing agents was administered via the mesenteric vein. Biliary excretion of glutathione disulfide increased temporarily after the administration and returned to its basal levels within 20 min. The biliary excretion of bilirubin decreased during the same period and returned to the former levels thereafter. Changes in bile flow rates remained within 20% of the basal levels. A linear correlation was found between the increments in the bile concentration of glutathione disulfide and the decrements in that of bilirubin. Furthermore, separate experiments revealed that reduction of hepatocellular glutathione per se had little effect on biliary excretion of bilirubin. The results thus indicate that the reduction of biliary excretion of bilirubin by glutathione-oxidizing agents was due to the increase in biliary excretion of glutathione disulfide, and suggest that a common biliary excretory mechanism is shared, at least partially, by bilirubin and glutathione disulfide in Sprague-Dawley rats. PMID- 8486219 TI - Fatal herpes simplex hepatitis type 2 in a post-thymectomized adult. AB - The authors report an unusual case of herpes simplex type 2 (HSV) hepatitis which presented as part of a systemic HSV infection accompanied by disseminated intravascular coagulation (DIC). The patient was a 49-year-old Japanese male who three months prior to admission underwent surgical resection of his thymus for an invasive thymoma. Postoperatively, he received a course of chemotherapy which included prednisone, cyclophosphamide, vincristine, and pinorubicin. After discharge from the hospital, he was put on a maintenance dosage of prednisone and cyclophosphamide. Two weeks prior to this admission, the patient developed rhinorrhea, chills and general fatigue. Routine follow-up laboratory tests revealed markedly elevated liver enzymes which led to his immediate hospitalization. The tentative diagnosis on admission was fulminant hepatitis with DIC. The patient's condition steadily worsened during his hospitalization and acyclovir was initiated on the 4th hospital day due to the possibility of HSV hepatitis. He died on the same day. Histopathology performed on the liver at autopsy revealed hepatic inclusion bodies of HSV with positive immunohistochemical detection of the HSV type 2 antigen. Our case is the first report of HSV hepatitis associated with the removal of the thymus secondary to thymoma. It supports previous observations of disseminated HSV infection being prevalent in those patients with disorders of cell mediated immunity. PMID- 8486221 TI - Changes of the extracellular matrix and cells producing it in acute liver injury. PMID- 8486220 TI - Role of hepatic sinusoidal cells in hepatic injury and fibrosis in the liver. PMID- 8486222 TI - Cytotoxic T lymphocyte activity and HB virus mutant in chronic HB virus carriers. PMID- 8486223 TI - Present status of fulminant hepatitis in Japan (1989-1991) AB - This paper describes the present status of fulminant hepatitis (FH) in Japan and focuses, in particular, on recent activities of the Research Subgroup of FH between 1989 and 1991. Both epidemiological and multi-institution surveys have demonstrated that the annual incidence of FH has decreased and that the survival rate is definitely improving, at least in the acute form of FH. Our goal, however, is to achieve a survival rate of greater than 50% overall for FH nationwide. To this end, a liaison across Japan of regional core hospitals with intensive care units has been organized to exchange opinions and experience in the clinical management of FH. Moreover, new specific and intelligent therapeutic modalities must be developed through basic research projects which focus on finding a means of inducing a necrotic liver to regenerate. PMID- 8486224 TI - Report of the research subgroup of autoimmune hepatitis/primary biliary cirrhosis. PMID- 8486225 TI - Interferon therapy in hepatitis C--refractory hepatitis--report of the research subgroup of treatment of chronic hepatitis. PMID- 8486226 TI - The role of cytotoxic T lymphocytes and inflammatory cytokines in the pathogenesis of acute viral hepatitis. PMID- 8486227 TI - Mechanisms and mediators in hepatic necrosis. AB - Necrotic processes may be restricted to individual cell types of the liver or afflict several liver cells sequentially. Noxious agents may induce necrobiosis by different mechanisms of injury. In many instances, however, similar or identical terminal processes are involved, e.g. accumulation of Ca2+ in cytosol or mitochondria, termination of nucleic acid and protein syntheses or membrane damage. Apoptosis may also be a relevant feature of hepatic necrosis. Inhibition of mRNA synthesis and post-translational glycosylations of proteins of the hepatocytes is instrumental in D-galactosamine-induced hepatocellular necrosis. An early event seen after administration of D-galactosamine plus endotoxin is an accumulation of neutrophilic granulocytes in the liver sinusoids. It results from the tumor necrosis factor (TNF)-alpha-induced adhesion of polymorphonuclear leukocytes to the sinusoidal endothelium and the vasoconstriction due to thromboxane A2 that is secreted by activated Kupffer cells. Temporal hypoxia and nutrient deprivation as well as the activation of the granulocytes with release of reactive oxygen species and proteinases appear to be severe consequences. Hypoxia followed by reperfusion (reoxygenation) must be considered as a mechanism of liver cell necrosis producing reactive oxygen species; oxygen radicals were reported to be signals for the activation of nuclear factor kappa B and thereby for the cytotoxicity of cytokines. PMID- 8486228 TI - Patterns and pathobiology of hepatic necrosis in chronic viral hepatitis. PMID- 8486229 TI - Network of cytokine and arachidonic acid cascade in acute hepatic failure. AB - When heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into mice and 7 days later a small amount of lipopolysaccharide (LPS) endotoxin was administered, most of the mice died of massive liver necrosis. In this liver injury model, cytokines, immunomediators, and eicosanoids, inflammatory products, were produced by Kupffer cells and liver-infiltrated macrophages, which were thought to participate, directly or indirectly, in the induction of liver cell damage. Furthermore, these two networks seemed to regulate each other. Thus, this regulatory mechanism might play an important role in the induction of liver cell injury. PMID- 8486230 TI - Design of hepatocyte-specific extracellular matrices for hybrid artificial liver. AB - For the development of an artificial liver which can assist multiple metabolic functions of liver, the effective cultivation of hepatocytes on substrate as extracellular matrix analogs was examined. Adult rat hepatocytes attached on an asialoglycoprotein model polymer, poly-N-p-vinylbenzyl-D-lactonamide (PLVA), formed anchored multilayer aggregates which had a stable three-dimensional structure when epidermal growth factor (EGF) and insulin were added to the culture medium. The formation of multilayer aggregates was also dependent on the specific cellular attachment mediated by asialoglycoprotein receptor of hepatocyte surface. Cells in the aggregates expressed higher level of albumin secretion and lower proliferative ability than those in monolayer cultures on collagen. It seemed likely that the cells in multilayer aggregates experienced stable differentiated states resembling in vivo status through the forming multilayer aggregates. The culture system described here has useful potentiality for the development of hepatic module systems for a hybrid artificial liver. PMID- 8486231 TI - Immunogenetics of autoimmune chronic active hepatitis. PMID- 8486232 TI - Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis. AB - We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease. PMID- 8486233 TI - Immunogenetic background of hepatitis B virus infection and autoimmune hepatitis in Japan. AB - Human leucocyte antigen (HLA)-typing was studied in 82 hepatitis B carriers and 15 cases of autoimmune hepatitis (AIH) to elucidate the genetic factors which may associated with the etio-pathogenesis of chronic hepatitis in Japan. There were two types of HLA phenotypes: HLA A2 was associated with the progression of the disease induced by HBV infection, and HLA A26 and DR5 were related to the retardation of the disease. A family study confirmed the strong association of these HLA phenotypes with the disease induced by HBV infection. In the analysis of AIH, HLA DR4 is a risk factor related to susceptibility of Japanese AIH which shows different clinical manifestations compared to HLA-DR3-positive AIH, dominantly observed in Western countries. These results suggest that genetic background as expressed by HLA, is an important factor in restricting the development of type B hepatitis and AIH, and can explain racial differences of disease susceptibility. PMID- 8486234 TI - Mutations of hepatitis B virus liver disease. AB - Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and patients with chronic liver disease. Several studies have suggested that the core antigen (HBcAg) could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CTL, the entire core region of HBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No significant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in small segment of 18 amino acids (codon 84 to 101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had advanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the 5 patients without mutation. These data suggest that this region with clustering mutations may play an important role in the pathogenesis of B viral liver disease, and the mutations in the region may be related to progressive liver disease. PMID- 8486235 TI - The biology and biochemistry of interferon-gamma and its receptor. AB - Interferon-gamma (IFN gamma) is an important immunomodulatory cytokine produced by activated T cells and NK cells that plays a pivotal role in promoting host defense. IFN gamma is distinguished from IFN alpha and IFN beta by its ability to regulate a number of immune functions. IFN gamma induces its biologic effects by interacting with a specific IFN gamma receptor expressed at the cell surface. Recently, IFN gamma receptors have been purified from human and murine cells and their cDNAs cloned and expressed. This work has revealed that IFN gamma receptors are 90 kDa, single chain glycoproteins that bind ligand with high affinity in a species specific manner. There appears to be only a single type of IFN gamma receptor that is expressed on nearly all cell types. Whereas this single polypeptide is sufficient to confer ligand binding and processing activity to transfected cells, a second, as yet undefined, component is required to form a functionally active IFN gamma receptor. The identity of this second component is currently being investigated. In addition, recent work has revealed novel structure-function relationships that exist within the IFN gamma receptor's intracellular domain. This work has shown that distinct portions of the intracellular domain are differentially responsible for mediating different biologic activities of the receptor. PMID- 8486236 TI - A role for cytokines as regulators of hepatic fibrogenesis. AB - It is evident that hepatic fibrogenesis is a complex process involving a cascade of cytokines which interact to enhance the expression of ECM. Cytokines involved early in this cascade may serve as proinflammatory agents or as stimulators of macrophage and Ito cell activation and proliferation, while those cytokines involved later in this process may be directly fibrogenic. Furthermore, we speculate that a balance between profibrogenic and antifibrogenic cytokines normally exists but in the presence of hepatic insults, a relative super abundance of the fibrogenic factors promotes the development of liver fibrosis. To date, most of the evidence supporting a role for cytokines in liver fibrosis has been obtained in in vitro systems or in animal models. We now need to extend these findings to man in order to determine whether a similar cascade of cytokines is important in the development of this pathologic process in man. Further delineation of these cytokines (as well as other profibrogenic soluble factors), and the mechanisms by which they act, are critical to our development of more rational forms of therapy for liver fibrosis. PMID- 8486237 TI - Conidial and mycelial-bound exo-pectinase of Aspergillus sp. AB - Intact conidia of Aspergillus sp. were able to degrade pectin 'in vitro' even when protein synthesis was inhibited, thus indicating the presence of cell bound pectinases. At least an exo-pectinase was found and this enzyme was also present in the mycelium of Aspergillus sp. Its presence was not dependent on the carbon source used for growth, suggesting its constitutive nature. This exo-pectinase could be released from conidia or mycelium by incubation at different pH values and the amount of enzyme released could be increased by treatments with chemical agents and hydrolytic enzymes. PMID- 8486238 TI - Correlation of cilofungin in vivo efficacy with its activity against Aspergillus fumigatus (1,3)-beta-D-glucan synthase. AB - (1,3)-beta-D-Glucan synthase is a cell wall synthesis enzyme that is the target of cilofungin, an antifungal agent of the lipopeptide class. Cilofungin's glucan synthase inhibitory activity, MIC, and effective dose 50% in a systemic infection mouse model tend to correlate for Candida albicans. This correlation is not seen in Aspergillus fumigatus. MICs for cilofungin against A. fumigatus were consistently > 125 micrograms/ml while the effective dose 50% in a systemic aspergillosis model was determined to be 20.6 mg/kg. To begin to understand this discrepancy, we examined the A. fumigatus glucan synthase. This cell wall enzyme was prepared and its activity was measured by [14C]-glucose incorporation from UDP-[U-14C]glucose into an acid insoluble polymer formed in the presence of alpha amylase. Enzyme activity in crude membrane preparations was measured in the presence of several antifungal agents. Enzyme inhibition results showed that 1 microgram/ml of papulacandin B, echinochandin B, aculeacin A and cilofungin all inhibited A. fumigatus glucan synthase activity (40-71%) while 1 microgram/ml of amphotericin B, fluconazole, ketoconazole and nikkomycin did not affect enzyme activity. A correlation was therefore established between the inhibitory effect of cilofungin on the A. fumigatus glucan synthase and the effective dose 50% obtained in a systemic aspergillosis mouse model. PMID- 8486239 TI - Expression of bacteriophage PhiX174 lysis gene E in Staphylococcus carnosus TM300. AB - Expression of the cloned PhiX174 gene E causes lysis of the Gram-negative bacterium Escherichia coli, which led to the proposal that a two-membrane system is necessary for the protein E lysis function. Gene E was cloned in an E. coli/Bacillus subtilis shuttle vector and expressed in the Gram-positive bacterium Staphylococcus carnosus TM300. Regulated gene E expression had a lethal effect on S. carnosus; however, no lysis was detected, lending support to the hypothesis. PMID- 8486240 TI - MetJ-mediated regulation of the Salmonella typhimurium metE and metR genes occurs through a common operator region. AB - In Salmonella typhimurium the metE and metR promoters overlap and are divergently transcribed. Three tandem repeats of an 8 bp sequence defined previously as the metE operator site for MetJ-mediated repression also overlap the -35 region of the metR promoter. Starting with a metE-lacZ.metR-galK double gene fusion, site directed mutagenesis was used to change nucleotides in each of the repeat units from the consensus sequence. Each mutation, along with the wild-type metE lacZ.metR-galK gene fusion, was cloned into phage lambda gt2. Regulation of the metE and metR genes was examined by measuring beta-galactosidase and galactokinase levels in Escherichia coli strains lysogenized with phage carrying the wild-type and mutant fusions. Mutations in each of the 8 bp repeat units disrupt MetJ-mediated repression for both the metE-lacZ and metR-galK gene fusions, suggesting that the metE and metR genes share a common operator site for the MetJ repressor. PMID- 8486241 TI - Identification of Aeromonas schubertii and Aeromonas jandaei by using a polymerase chain reaction-probe test. AB - Two oligonucleotide primers were used in a polymerase chain reaction-protocol to amplify a region (approx. 850 bp) of the 16S rRNA gene of Aeromonas schubertii and Aeromonas jandaei. Hybridization of the polymerase chain reaction products to specific internal probes provided a highly specific method for the identification of these two species. PMID- 8486242 TI - Amino acid sequence of heat-labile enterotoxin from chicken enterotoxigenic Escherichia coli is identical to that of human strain H 10407. AB - The DNA sequence of heat-labile enterotoxin from the chicken enterotoxigenic Escherichia coli 21d strain was determined by direct dideoxy sequencing of polymerase chain reaction (PCR)-amplified DNA and was compared with those of heat labile enterotoxins from porcine and human enterotoxigenic E. coli strains EWD 299 and H 10407. The structural genes of the A and B subunits of chicken heat labile enterotoxin were identical to those of human heat-labile enterotoxin from the human H 10407 strain. Moreover, 67 base pairs of the upstream and 60 base pairs of the downstream region of the chicken heat-labile enterotoxin gene were also identical to that of the human heat-labile enterotoxin from strain H 10407. However, the patterns of plasmids from the 21d and H 10407 strains were different. The 21d strain had no band corresponding to the 42-MDa plasmid of the H 10407 strain encoding the heat-labile enterotoxin gene but it had a smaller plasmid. These data suggest that although the DNA sequence of chicken heat-labile enterotoxin is identical to that of human heat-labile enterotoxin, the plasmid encoding the chicken heat-labile enterotoxin gene in the chicken might be different from that encoding the human heat-labile enterotoxin gene in the H 10407 strain. PMID- 8486243 TI - Local and systemic immunity against Streptococcus pneumoniae: humoral responses against a non-capsulated temperature-sensitive mutant. AB - Temperature-sensitive mutants of Streptococcus pneumoniae were isolated after chemical mutagenesis. Intranasal immunization with temperature-sensitive mutant J/3 induced higher levels of circulating antibody than those obtained after immunization with the heat-killed parental wild type. Moreover, local immunization with mutant J/3 induced high levels of anti-S. pneumoniae IgG and IgA in the lower respiratory tract, whereas only moderate IgG (and no IgA) antibodies were detected in lung lavage fluids from mice immunized intranasally with the heat-killed strain. PMID- 8486244 TI - Interaction of a trypsin-like enzyme of Porphyromonas gingivalis W83 with antithrombin III. AB - We have previously observed that trypsin-like activity in Porphyromonas gingivalis culture supernatants is inhibitable by the plasma arg-serpin antithrombin III (ATIII). This report demonstrates that a partially purified P. gingivalis trypsin-like enzyme (M(r) 47,000) is inhibited by ATIII with an association rate constant (k(ass)) of 5.65 x 10(4) M-1 s-1 but does not form SDS stable complexes. Heparin enhances the k(ass) and stabilizes the complexes but in either case such inhibition is temporary and results in ATIII inactivation by reactive centre proteolysis between R393-S394. In the absence of heparin this is accompanied by N-terminal cleavage between K39-I40. PMID- 8486245 TI - Nucleotide sequence of the gene coding for Clostridium barati type F neurotoxin: comparison with other clostridial neurotoxins. AB - The neurotoxin gene from Clostridium barati ATCC43756 was cloned as a series of overlapping polymerase chain reaction (PCR) generated fragments using primers designed to conserve toxin sequences previously published. The toxin gene has an open reading frame (ORF) of 1268 amino acids giving a calculated molecular mass of 141,049 Da. The sequence identity between the C. barati ATCC43756 and non proteolytic C. botulinum 202F neurotoxins is 64.2% for the light chain and 73.6% for the heavy chain. This is much lower than reported identities for the type E neurotoxins from C. botulinum and C. butyricum (96% identity between light chains and 98.8% between the heavy chains). Previously identified conserved regions in other botulinal neurotoxins were also conserved in that of C. barati. An ORF upstream of the toxin coding region was revealed. This shows strong homology to the 3' end of the gene coding for the nontoxic-nonhemagglutinin (NTNH) component of the progenitor toxin from C. botulinum type C neurotoxin. PMID- 8486246 TI - Degradation of 2,4-dihydroxybenzoate by Pseudomonas sp. BN9. AB - The aerobic degradation of 2,4-dihydroxybenzoate by Pseudomonas sp. BN9 was studied. Intact cells of Pseudomonas sp. BN9 grown with 2,4-dihydroxybenzoate oxidized 2,4-dihydroxybenzoate but not salicylate. Cell-free extracts of Pseudomonas sp. BN9 converted 2,4-dihydroxybenzoate after the addition of NAD(P)H. A partially purified protein fraction converted 2,4-dihydroxybenzoate with NADH to 1,2,4-trihydroxybenzene. 1,2,4-Trihydroxybenzene was converted by a 1,2-dioxygenase to maleylpyruvate, which was reduced by a NADH-dependent enzyme to 3-oxoadipate. 2,4-Dihydroxybenzoate 1-monooxygenase, 1,2,4-trihydroxybenzene 1,2-dioxygenase and maleylpyruvate reductase were induced in Pseudomonas sp. BN9 after growth with 2,4-dihydroxybenzoate. PMID- 8486247 TI - Expression of human alpha 1 interferon genes in vectors containing tandemly located promoters recognized by two different RNA polymerases (Escherichia coli and T7). AB - An expression vector containing two tandemly located promoters (T7 and P1) and two transcription terminators recognized by two different RNA polymerases (T7 RNA polymerase and Escherichia coli RNA polymerase) was constructed. Human alpha 1 interferon gene variants were cloned in this vector and their expression was studied in E. coli strains containing [E. coli BL2I (DE3)] or devoid (E. coli BL21) of the gene for the T7 RNA polymerase. We report that simultaneous activity of the two promoters reduces the level of gene expression when compared with the levels of expression corresponding to either P1 or T7 promoter alone. PMID- 8486248 TI - Identification of the transcriptional start site of the cyd operon from Escherichia coli. AB - The cydAB operon encodes the two subunits of the cytochrome bd ubiquinol oxidase from Escherichia coli. This enzyme is one of two terminal oxidases in the aerobic respiratory chain of E. coli. It has been demonstrated that expression of the cyd operon is transcriptionally regulated by oxygen via both the fnr and arcA gene products. Whereas arcA clearly serves as a positive regulator at low oxygen tension, there is no consensus concerning the role of the fnr gene product (FNR). In this paper, the transcriptional start site of the cyd operon is identified at position -287 with respect to the translational start. This is located 53 basepairs downstream from the center of dyad symmetry of the putative FNR recognition sequence. PMID- 8486249 TI - Ubiquinone systems of Coccidioides immitis, the causative agent of coccidioidomycosis. AB - The ubiquinone (coenzyme Q) systems of eleven strains of Coccidioides immitis were determined by high performance liquid chromatography (HPLC). The ubiquinone profile of the fungi was shown to be homogeneous: in all of the strains, ubiquinone-10 (Q-10) was demonstrated to be the major component, with Q-9 as a minor component. The results imply that the ubiquinone system may serve as an additional phenotypic criterion for identifying the fungus. PMID- 8486250 TI - [Genetic control of mitotic recombination in Saccharomyces cerevisiae yeast]. AB - A review of research on genetic control of mitotic recombination in the yeast Saccharomyces cerevisiae is presented. The genes controlling different stages of mitotic recombination have been considered. Possible relationship of the recombination and repair functions of these genes is under discussion. PMID- 8486251 TI - [Existence of a negative correlation in the level of satellite DNA III and the number of rRNA gene repeats, localized on the short arms of human acrocentric chromosomes]. AB - Relationship between the data on hybridization of the cloned sequences of the satellite DNA III located in the short arm of the acrocentric chromosomes and the hybridization data on the cloned fragments of 28S and 18S rRNA genes, as well as the transcriptional activity of human nucleolus organizer was studied. Negative correlation between the content of the satellite DNA III and the number or expression of rRNA genes was shown. PMID- 8486252 TI - [Specific proteolysis of Clostridium thermocellum endoglucanase upon heterologous expression in Escherichia coli cells]. AB - The cel(1) gene of Clostridium thermocellum encoding endoglucanase cloned earlier in Escherichia coli was deleted at specific sites and fused with the E. coli gene lacZ'. Analysis of heterologous expression of the produced variants was performed. It was established that the post-translational modification of the clostridial endoglucanase in E. coli involves a membrane-linked N-terminal cleavage of 6 kDa polypeptide during secretion through the cytoplasmic membrane and a C-terminal cleavage of 4 kDa protein not related to the secretion. A comparative study of the authors' and literature data supports the suggestions that: (i) the cel(1) cloned in this laboratory is a deleted variant of the cloned cel(1) gene of C. thermocellum described previously by other authors, and (ii) the C-terminal proteolysis of the endoglucanase precursor takes place in a linker region connecting the catalytic and cellulose binding domains. An account of similar kind of proteolysis responsible for multiple forms of cellulolytic enzymes is given. PMID- 8486253 TI - [In vivo and in vitro study of plasmid fragments from Ca2+-dependent Yersinia pestis (Lehmann, Neumann)]. AB - The bank of the HindIII, EcoRI and PstI fragments of Yersinia pestis Ca(2+) dependence plasmid (pCaD) was constructed and used as molecular probes, combined with the restriction analysis to map pCaD. Experiments on laboratory animals showed two subfragments of the fifth HindIII fragment to impart virulence, invasiveness to the plasmidless avirulent strains of Y. pestis, Y. pseudotuberculosis and Escherichia coli, and the protective activity to Y. pestis clones, while the original fifth HindIII fragment possessed no such property. PMID- 8486254 TI - [Rec41--a new gene, participating in the control of recombination in Saccharomyces cerevisiae yeast]. AB - We isolated a collection of rec- mutants. The mutant rec41 from this collection was studied in detail. The mutant demonstrated a reduced level of interplasmid recombination, did not grow at the elevated temperature (36 degrees C) and was sensitive to gamma-rays but not to ultraviolet irradiation. The rec41-1 mutation behaved as a semidominant nuclear mutation. Our study on inter- and intraplasmid recombination suggested that the rec41-1 mutation decreased the level of crossing over events significantly and the frequency of gene conversion events at a lower degree. We postulate that rec41 mutation reduces the efficiency of double stranded break repair and this results in high sensitivity of mutant cells to methylenmethan-sulfonate and ionizing radiation. Using gamma-sensitivity of the mutant cells we isolated a rec41-1 complementing plasmid from a yeast genomic DNA library. The mapping of plasmid integration site allowed us to localize the REC41 gene on the left arm of the VII chromosome nearby LYS4 and CDC43 genes. PMID- 8486255 TI - [Characteristics of the bacteriophage N15 lysogenic conversion gene and identification of its product]. AB - The plasmids containing EcoRV fragments of N15 phage DNA and inhibiting the adsorption of T1, phi 80 and N15 phages were selected and characterized. The N15 lysogenic conversion gene (cor) was mapped in the SalI-PstI fragment of 700 bp in length which is localized near SalI site with the coordinates 40.1 kb on the N15 plasmid prophage DNA physical map. The cor gene was recloned on a multicopy vector in the both possible orientations and its expression was shown to occur most probably under control of its own promoter in the direction from SalI to the ClaI site of the SalI-PstI fragment. The molecular weight of the Cor protein (7-9 kD) was determined by the analysis in the system of mini-cells. Initiation of transcription to wards the cor gene from the external promoter led to the bacteriostatic effect. PMID- 8486256 TI - [Mutagenesis of enzyme loci, induced in megaspores of Pinus sylvestris L. by ionizing radiation from the accident at the Chernobyl Atomic Power Plant]. AB - Mutagenesis of alleles of 20-allozyme loci was studied using the electrophoresis methods in polyacrylamide gel in seeds of Pinus sylvestris within the 30 km zone of the Chernobyl NNP and the limits of contamination levels by Cs-137 from 5 up to 600 Cu/km (the absorbed doses being 0.5 to 10 Gy). The frequency of emergence of corresponding mutations which change the synthesis of enzymes in endosperms within the zone constituted on the average 2.7-10 per gene as compared with 0.6 10 in control version. Linear dependence was observed between low doses absorbed and the frequency of gene mutations, while in case of high doses this decreased. Genetic effectivity was 0.001 mutations/locus/Gy. Various radiosensitivity levels were shown among the loci studied. Spontaneous level of mutations frequency in P. sylvestris populations was found to be within the limits of 0.5 to 1.5 Gy under conditions of the 30 km zone. The high rate of mutagenesis was revealed in seeds of the first two post-accident reproductions. PMID- 8486257 TI - [Effect of sperm genotype on the segregation of homologs in male mice, heterozygous for an aberrant chromosome 1]. AB - The aberrant chromosome 1 with two large homogeneously staining insertions was isolated from wild populations of Mus musculus. Specific features of aberrant chromosome were described elsewhere. These include preferential entry of the chromosome into the oocyte of heterozygous females, increased mortality of homozygotes, decreased fertility of homozygous females. The data obtained indicated that segregation of homologues in heterozygous females depended on which spermatozoon entered the oocyte, prior to the second meiotic division: meiotic drive is powerful when the spermatozoon bore the normal chromosome 1, and homologue segregation got normalized during MII when the spermatozoon bore the chromosome 1 with insertions. Experimental data are adduced and explanations offered for the phenomenon observed. PMID- 8486258 TI - [Temperature modification of the mutation process and heat shock proteins]. AB - Heat shock protein synthesis and mutagenesis (X-chromosome losses induced by radiation and high temperature) were studied in different. Drosophila melanogaster strains. Two models (strain l(1)ts403 with the defect in heat shock protein synthesis and the heat-resistant T strain with a specific reaction to the extreme temperature differing from the wild type strains) were used. The correlation between heat shock protein synthesis and the effect of synergism in the action of radiation and heat shock was revealed. It was concluded that HSPs are one of the components in mutagenic processes. PMID- 8486259 TI - [Cytogenetic analysis of recombination interactions]. AB - Chiasma interference between separate regions of chromosomes was studied in three phylogenetically distant species. All these species displayed the similar patterns of chiasma interference. Chiasma completely suppressed recombination in the regions next to chiasma within a chromosome's arm. The level of crossing-over suppression decreased non-linearly with increase in a distance between the chiasma and the region under analysis. Some kind of the threshold effect was observed. In some cases, negative interference between the regions rather remote from each other was noted. Polarity of interference was revealed: interstitial chiasma suppressed recombination in the proximal (in relation to the centromere) direction more effectively than in the distal direction. Some regions belonging to the different arms of the same chromosome were shown to be able to interfere. PMID- 8486260 TI - [Molecular-genetic analysis of expression features of the evolutionary conservative neurogene Nc73EF of Drosophila melanogaster]. AB - Molecular-genetic analysis of the Nc (neural conserved) genome sequence of Drosophila melanogaster located at the position 73EF of Drosophila melanogaster was performed. The Nc73EF sequence was shown to be expressed in the nervous system of Drosophila. We constructed the restriction map of this sequence and revealed the main RNA-coding fragment in the 5'-3' orientation. The RNA-dot analysis data demonstrated that expression of the Nc73EF transcripts took place mainly in the nervous system. Hybridization with the human brain poly(A)+RNA confirmed the basic RNA-coding fragment to be evolutionary conservative. Southern blot analysis showed this fragment to be unique in the Drosophila genome. Northern blots detected three transcripts of this DNA fragment. PMID- 8486261 TI - [Genetic disorders in laboratory mice, exposed in the region of the Chernobyl Atomic Power Plant four years after the accident]. AB - Mice (CBA x C57BL)F1, of both sex and males C57BL were exposed within the 10 km zone of the Chernobyl Nuclear Power Station during 14, 22 and 34 days. Genetic damages of chronic radiation in the exposed adult mice, and in the course of embryogenesis, was studied. The gonadal absorbed radiation doses of the exposed mice varied from 0.5 to 1.5 Gy. The frequencies of dominant lethal mutations, abnormal sperm heads and reciprocal translocations linearly increase with increasing absorbed radiation doses. Among 49 males exposed at the embryonal stage one male heterozygote for reciprocal translocation was revealed. In other males of this group, reciprocal translocation yield was low. No uniform dependence of genetic effects from mice genotype was revealed. PMID- 8486262 TI - [Interrelation of genetic dimorphism of ear wax and the level of apolipoproteins with atherogenesis and longevity in the Lithuanian population]. AB - Genetic dimorphism of the cerumen was studied in a random sample from the Lithuanian population (N = 253), among the patients with the most atherosclerotic risk, from different age groups (N = 276) and in a cohort of long-living (N = 117). Simultaneously, the levels of apolipoprotein (apo- A-1, B, E) were determined in blood sera of the males-donors, long-living and elderly individuals depending on the phenotypes for ear wax consistency. The prevalence of frequency of the w gene for humid cerumen in children suffering from the insulin-dependent diabetes mellitus was found as compared with populational sample--0.8293 and 0.6024, respectively (P < 0.002). On the contrary, essential increase in frequency of the d gene responsible for dry cerumen in long living was found as compared with the control--0.5311 and 0.3976, respectively (P < 0.01). An absence of differences in the concentrations of w and d alleles among the patients with coronary artery atherosclerosis and the populational control indicated that the genetic characters under study exerted no marked change in incidence of atherogenesis. However, the ratio apoB/apoA-1 proved higher in the donors with humid ear wax than in those with the dry variant under P < 0.06, which can stimulate this disease. The results of this study support the statement that low level of apoB and especially apoB/apoA-1 may be one of the longevity markers. PMID- 8486263 TI - [Repeating sequences, organizing the telomeric region of chromosomes from the eukaryotic genome]. AB - The telomeric regions of the eukaryotic genome are composed of different types of the repeated DNA sequences. Extended subtelomeric repeats (STR) are located close to the terminating repeats (TR) at the extreme ends of the chromosomes. The first part of the review is devoted to the TR sequences. All of them are the simple satellite-similar tandem repeats (T/A)1-8 G1-8. TR, as a substrate of specific telomere elongating enzyme telomerase, controls the whole replication of the chromosomal DNAs. Information accumulated up to this time is sufficient to ascertain the principal uniformity of the structure, the functions and organization of TR in all eukaryotic genomes. The second part of the review is devoted to the STR sequences. The STRs are prolonged repetitive sequences localized between the TR cluster and non-repetitive genes. The STRs have been identified in rye, yeast, Trypanosoma, Drosophila, Chironomus, murine and human genomes. It can be seen from the analysis of experimental results that the STRs of different organisms may have general properties. The information about the functions of STRs is now being obtained for only the STR of Drosophila. The STR is the complex repetitive family located both in telomeres and in heterochromatin. The sequences from the family were recently shown to be capable of translocation and curing destroyed chromosomal ends. According to the latest information, the STR sequences are organized in two different types of clusters in the Drosophila genome. The types have different organization and different genome localization. Is the organization of both telomeric and heterochromatin regions of the Drosophila genome from the same structural elements common for higher eukaryotes or it is the characteristic feature of the Drosophila genome only, is to be cleared. PMID- 8486264 TI - [Drosophila beta-heterochromatin: molecular organization and function. Characteristics of the DNA sequences from proximal beta-heterochromatin, associated with the nuclear envelope of Drosophila melanogaster]. AB - To study the nucleotide sequence from the pericentric heterochromatin associated with the nuclear envelope, a residual DNA was extracted from the DNAse-treated nuclear lamins of Drosophila melanogaster tissue culture cell line Kc. The isolated DNA was cloned in lambda vector. The DNA library obtained was screened for the clones homologous to the pericentric heterochromatin. The experiments on in situ hybridization to the polytene chromosome of the nurse cell nuclei of the strain fs(2) B assigned the reiterated sequence, homologous to the lamin DNA clone, to the nuclear envelope associated regions of the proximal beta heterochromatin which is known to undergo structural reorganization during cell differentiation. The nucleotide analysis of 300 bp from this sequence has established the presence of 21 bp and 300 bp d(GT/CA), 12 bp AT-box, the regions of recognition of the nuclear factor and the inverted repeats. PMID- 8486265 TI - [Drosophila beta-heterochromatin: molecular organization and function. Cloning and molecular biological analysis of the lambda 20 DNA fragment from Drosophila melanogaster beta-heterochromatin]. AB - To isolate the DNA sequences specific for the pericentric heterochromatin of Drosophila we used two CREST-autoimmune sera which bind in the Western-blot analysis the nuclear antigens of 30 kDa, 43 kDa and 45 kDa molecular weight. Cloning of the DNA fragments associated with these CREST-specific proteins of Drosophila resulted in obtaining 8 clones. One of them, lambda 20, hybridized mainly to the chromomcenter of polytene chromosomes. The further analysis indicated that the lambda 20 DNA might belong to the proximal beta heterochromatin of the polytene chromosomes of D. melanogaster. PMID- 8486266 TI - [The nature of the emergence of His+-revertants in Salmonella typhimurium]. AB - The His(-)-->His+ spontaneous reversion of the Salmonella typhimurium alleles hisD3052 and hisG46 was studied. The expected jackpot distribution of His+ revertants was not observed in the fluctuation tests. The experimental distributions were close to Poisson. It was also shown that the mean number of His+ reversion events and the mean number of revertants per plate were similar. These data demonstrate that the His+ reversion occurred under the influence of histidine starvation. At the same time, kanamycin resistant mutants had the jackpot distribution. Selection for His+ revertants did not increase the Kans- >Kanr mutations. PMID- 8486267 TI - [Modification with ascorbic acid of the level of spontaneous and induced chromosome aberrations and sister chromatid exchanges in lymphocytes of workers in contact with molybdenum salts]. AB - Five workers of molybdenum gilding at the metallurgical works were observed prior to and after administration of ascorbic acid. Tests for chromosomal aberrations (CA) and sister chromatid exchanges (SCE) were used as the criteria for estimation. Individual sensitivity to the chemicals was revealed in the workers. Administration of ascorbic acid caused reduction of the level of chromosomal structural rearrangements. PMID- 8486268 TI - [Formation of heat stability of gametes in Drosophila oogenesis and connection of this property with the mutation process]. AB - It has been demonstrated that heat resistance (and radiosensitivity) of the germ cells at all stages of oogenesis in the females of heat resistant drosophila line (T) is being formed during ontogenesis and depends on the environmental temperature. These characteristics were retained at the stage of imago, even in the cases of temperature changes (from +32 to +25 degrees C, or from +25 to +32 degrees C). The intensity of induced mutagenesis (by X-rays and high temperature) which was evaluated for the frequency of dominant lethal mutations and X chromosome loss depended on the temperature during development, but depends on no temperature at the time of treating imago with the mutagenic agents. It is suggested to be a result of the participation of heat shock proteins in repair of DNA damages. PMID- 8486269 TI - [Phylogenetic connection of aboriginal dogs of the Caucasus, Central Asia, and Siberia with species from Europe and Japan, detected by an analysis of polymorphism of blood proteins and enzymes]. PMID- 8486270 TI - [Analysis of peripheral blood serotonin in domesticated silver foxes (Vulpes vulpes) as a major gene marker of domesticated behavior]. AB - A segregation analysis of inheritance of the blood serotonin level in a domesticated silver fox population was performed (104 foxes from 4 pedigrees). The results of the analysis point to the effect of a major-gene in the control of this quantitative trait (dominance coefficient of lower level is 0.79), and suggest that breeding for domestic behavior is accompanied by selection against heterozygosity with respect to this major-gene. The lower blood serotonin level revealed in more domesticated foxes (p < 0.02) may be a consequence of this. PMID- 8486271 TI - [Interconnection of the functional activity of nucleolar organizer regions of chromosomes with human reproductive pathologies]. AB - Comparative analysis of transcriptional activity of human nucleolus organizer regions (NOR) of the chromosomes in the group of the control phenotypically healthy individuals (I) and in the spouses with repeated spontaneous abortions (II) was conducted in an attempt to verify the hypothesis: whether elimination of zygotes having received a very large or very small number of the copies of active rRNA genes may serve as a factor decreasing the fecundity of some spouses? It has been shown that the groups I and II have no differences in total activity of 10 NOR (Ag staining, rating estimation). At the same time, the II group is characterized by higher, in comparison with the I, heterogeneity of Ag-NOR variants in homologues of 5 nucleolus-organizing chromosomes. As a result, in the individuals of the group II the gametes are formed which are more heterogenous than in the group I for the Ag-NOR pattern variants. The imitation computer experiments revealed that in the group II elimination of zygotes as a consequence of inherited Ag-NOR variants combination should occur more frequently (in 22.2% cases) than in the group I (15.9%), p < 0.05. Thus, the hypothesis under test was substantiated in the present study. PMID- 8486272 TI - [Genetic HLA system in the Northern Khant population compared with other Ugro Finnish peoples]. AB - The northern khants different from the east khants in frequencies of some genes from the HLA-A, B, Cw system and in the absence of the disequilibrium linkage. Population-genetic mechanisms underlying HLA polymorphism differences between the two groups of khants which may have resulted during the historical development of these groups or from the difference of climate conditions under which these ethnic groups had lived, are under discussion. PMID- 8486273 TI - [Differential fertility in the Kharkhov population]. AB - The distribution of the number of pregnancies, births and abortions in the Kharkov population was analysed in the cohort of women with the completed fertility. The mean number of pregnancies per woman was 3.77 for the first generation and 4.30 for the second generation. The mean number of births in the first and second generations was 1.47 and 1.35. The Crow's Index of the opportunity for selection and its components connected with differential mortality was estimated. The value of the Crow's Index was decreased during one generation from 0.56 to 0.35. In the women of the second generations having high and secondary education, the number of pregnancies was 3.72 and 4.38, respectively, the Crow's Indexes being 0.33 and 0.35. PMID- 8486274 TI - [Molecular cloning of threonine biosynthesis genes from Propionibacterium shermanii in Escherichia coli cells]. AB - Cloning the genes for threonine biosynthesis from Propionibacterium shermanii was performed in Escherichia coli cells using the plasmid vector pVZ361. The cloned genes were identified via complementation of thrB, thrC, thrA1 and thrA2 mutations of E. coli. The gene complementing thrB of E. coli was located within a 5.1 kb fragment of P. shermanii chromosomal DNA. The cloned DNA fragment hybridized with a chromosomal fragment of P. shermanii of the same size. The plasmid pSPt4 (with the thrB gene) was digested with Sau3A and ligated with the BamHI-restricted pUC19 vector. The 1.8 kb DNA fragment of P. shermanii was shown to complement the thrB gene function in E. coli cells. PMID- 8486275 TI - Lambda SK diphasmids: phage lambda vectors for genomic, jumping, linking and cDNA libraries. AB - Fifteen new phage lambda vectors are discussed: lambda SK4, lambda SK6, lambda SK10, lambda SK16, lambda SK17, lambda SK20, lambda SK21, lambda SK22, lambda SK23, lambda SK24, lambda SK25, lambda SK27, lambda SK28, lambda SK40 and lambda SK41. Their structural and functional features facilitate the implementation of a number of new strategies and cloning procedures which simplify, economize and vastly improve the utility and efficiency of library construction in lambda vectors. Such improved strategies and examples of their application, with particular reference to jumping and linking libraries, are presented. PMID- 8486276 TI - Cloning and sequence analysis of an Escherichia coli gene conferring bicyclomycin resistance. AB - We have cloned and sequenced DNA from Escherichia coli that, when present in a high-copy-number plasmid, confers resistance to the diketopiperazine antibiotic, bicyclomycin (Bc). The DNA includes a 378-amino-acid open reading frame (ORF), disruption of which results in the loss of Bc resistance. This ORF contains the BcR gene. Studies using the minicell expression system reveal that a polypeptide of 31 kDa is produced from this cloned region. The ORF maps at 47.1 min on the E. coli genome map. Sequence comparison between the translated ORF and a protein database reveal between 26.5 and 23.4% aa sequence homology to bacterial transmembrane (TM) proteins including those mediating chloramphenicol (Cm) and tetracycline (Tc) resistance and an arabinose-proton symport protein. Sequence analysis using the Diagon program showed the BcR gene product (BcR) had homology with the N-terminal regions of the CmR and TcR-encoded proteins and weak N terminal homology with the arabinose-proton symport protein. Hydropathy profiles of the BcR protein and CmR products show a striking similarity, both having twelve predicted TM domains. PMID- 8486277 TI - Cloning and sequencing of the Lactococcus lactis subsp. lactis groESL operon. AB - The operon (groESL) coding for the Lactococcus lactis subsp. lactis heat-shock proteins GroEL and GroES, has been isolated and its complete nucleotide (nt) sequence determined. A set of degenerate PCR primers, deduced from amino acids which are conserved in a number of prokaryotic GroELs, were synthesized and used to amplify a 957-bp fragment. This PCR fragment was used as a probe to isolate a 5.0-kb EcoRI chromosomally derived fragment. A region of this 5.0-kb EcoRI fragment was sequenced and revealed that the groES gene was located 5' to groEL. This sequence was then used to design a set of inverse PCR primers and a 2.5-kb HindIII fragment was cloned which contained the region 5' to groEL. The complete nt sequence of the groESL operon was determined from overlapping fragments. It revealed that the groESL operon was preceded by a stem-loop structure and the promoter appears similar to most L. lactis subsp. lactis and other Gram+ bacterial promoters. Northern analysis demonstrated that the groESL operon is under tight regulation and a dramatic induction of mRNA synthesis occurs within 15 min after heat shock. PMID- 8486278 TI - Sequence and transcriptional analysis of the nourseothricin acetyltransferase encoding gene nat1 from Streptomyces noursei. AB - We have determined the nucleotide (nt) sequence of nat1, a gene encoding nourseothricin (Nc) acetyltransferase (AT) from Streptomyces noursei, and its transcriptional start point (tsp). The nt sequence upstream from the coding region is completely different from that of the stat gene (encoding streptothricin AT) from Streptomyces lavendulae [S. Horinouchi, K. Furuya, M. Nishiyama, H. Suzuki and T. Beppu, J. Bacteriol. 169 (1987) 1929-1937], even though the nt sequences of the two genes and the deduced amino acid (aa) sequences of the two enzymes show a high degree of similarity. Another stat gene, derived from a Gram-negative plasmid, showed only deduced aa similarity, but not nt sequence similarity, to the above two. A database search for related aa sequences did not reveal any clear-cut homologies to other types of protein. A multiple aa sequence alignment of several ATs is presented. PMID- 8486279 TI - Sequence of the Streptomyces thermoviolaceus CUB74 alpha-amylase-encoding gene and its transcription analysis in Streptomyces lividans. AB - The alpha-amylase (Amy)-encoding gene (amy) of Streptomyces thermoviolaceus CUB74, previously cloned in Escherichia coli and S. lividans and localised on a 1.7-kb BamHI-SphI genomic DNA fragment, has been sequenced. A single open reading frame of 1380 bp, which could encode an Amy protein of 460 amino acids (aa), was identified. The deduced aa sequence of the thermophilic Amy is similar (up to 69.5%) to the mesophilic Amy of S. griseus, S. limosus, S. venezuelae and S. hygroscopicus. A 40% sequence similarity was found between the extracellular forms of the S. thermoviolaceus and the pig pancreatic Amy. In addition, the activity of the S. thermoviolaceus Amy is strongly inhibited by tendamistat, a potent inhibitor of mammalian Amy. The nucleotide sequence at the 5' end of amy was able to initiate transcription in S. lividans and contains a promoter whose sequence is identical to the promoters of the S. limosus, S. venezuelae and S. griseus amy. PMID- 8486280 TI - A random mutagenesis procedure: application to the POL3 gene of Saccharomyces cerevisiae. AB - To obtain a broad spectrum of mutations in the POL3 gene, we have developed an efficient random mutagenesis procedure. Partially extended, primed, single stranded templates were used for forced misincorporation of non-complementary nucleotides, extended to completion and ligated. Linear fragments of the resulting amplified mutagenized library were then used to transform a Saccharomyces cerevisiae strain by the marker replacement technique. This procedure has proven to be very efficient when applied to the C-terminal moiety of POL3, yielding 24 temperature-sensitive mutants and six extragenic revertants. PMID- 8486281 TI - Analysis of 5' flanking sequences from the Schizosaccharomyces pombe cdc2 gene. AB - Previously, the sequence of the Schizosaccaromyces pombe cdc2 gene was reported to begin at a HindIII site, 141 nucleotides (nt) upstream from the ATG start codon [Hindley and Phear, Gene 31 (1984) 129-134]. We have extended the sequence of the 5' untranslated region of the gene to a PsI site at -822 nt. We demonstrate by primer extension analysis that transcription of the gene initiates at one major point 180 nt upstream from the ATG start codon. Since the 822-nt fragment extending from the PstI site to the start codon has been used in many studies as the promoter for cdc2 [Booher and Beach, Mol. Cell. Biol. 6 (1986) 3523-3530; Carr et al., Mol. Gen. Genet 218 (1989) 41-49; Gould and Nurse, Nature 342 (1989) 39-45], we investigated the strength of this promoter element relative to the SV40 early promoter, a promoter known to work very well in S. pombe [Jones et al., Cell 53 (1988) 659-667]. We confirm that the cdc2 gene fragment has significant promoting activity, albeit 20- to 60-fold less than the SV40 early promoter, when assayed in S. pombe. PMID- 8486282 TI - Sequence of the Candida albicans erg7 gene. AB - The nucleotide sequence of the Candida albicans erg7 gene, which complements erg7 mutants of Saccharomyces cerevisiae and restores oxidosqualene cyclase activity, was determined. The gene encodes a 728-aa protein that displays homology with squalene-hopene cyclase, providing further evidence that erg7 is the gene encoding 2,3-oxidosqualene cyclase. PMID- 8486283 TI - Versatile suicide vectors which allow direct selection for gene replacement in gram-negative bacteria. AB - A set of vector plasmids which greatly facilitate gene replacement and reverse genetics in many Gram-negative bacteria was constructed. These vectors are based on the P15A origin of replication (ori) and incorporate sacB from Bacillus subtilis, which is inducible by sucrose and is lethal when expressed in Gram negative bacteria. The vectors also have a convenient antibiotic-resistance marker (gentamicin resistance) and the lacZ alpha system which allows blue/white selection of cloned fragments. Three different multiple cloning sites, allowing several distinct cloning and gene replacement strategies, are available in the 5' end of lacZ on different vectors. One of these cloning sites, which we synthesised, contains only a NotI-SmaI-NotI sequence; this allows access to most of the restriction sites within the cloned fragment for the purpose of insertion of various cassettes and interposons. The vectors carry the mob region from the broad-host-range plasmid RP4 and are thus mobilizable by conjugation into a wide range of Gram-negative bacteria; since they will not replicate in bacteria other than enterobacteria, they function as 'suicide' vectors. Variants of the vectors carrying the phage lambda cos site were also constructed. We have used these vectors to carry out gene replacement experiments in the fixN region of Rhizobium leguminosarum and have demonstrated that they are extremely useful in eliminating long and tedious screening procedures. PMID- 8486284 TI - A family of Ustilago maydis expression vectors: new selectable markers and promoters. AB - The cDNA expression system for Ustilago maydis has been expanded to include different selectable markers and promoters. These new elements allow the simultaneous expression of two genes in the same transformant. PMID- 8486285 TI - Sequences of genes encoding naphthalene dioxygenase in Pseudomonas putida strains G7 and NCIB 9816-4. AB - The multicomponent enzyme, naphthalene dioxygenase, initiates the metabolism of naphthalene by Pseudomonas putida strains G7 (PpG7) and NCIB 9816-4 (Pp9816-4). The genes involved (nahAaAbAcAd) are encoded by the NAH7 and pDTG1 plasmids, respectively, and form part of the nah operon. The locations of the structural genes were determined on previously cloned fragments of DNA. The nucleotide (nt) sequences were determined for nahAaAb from Pp9816-4 and for nahAaAbAcAd from PpG7. The appropriate open reading frames were identified using N-terminal amino acid sequences determined from the purified proteins. The two nt sequences showed 93% homology, with the least homology seen upstream from the promoter region. PMID- 8486286 TI - Cloning and sequencing of the Serratia marcescens gene encoding a single-stranded DNA-binding protein (SSB) and its promoter region. AB - The gene (ssb) coding for a single-stranded DNA-binding protein (SSB) was identified on a 1.2-kb EcoRI-SalI fragment cloned from chromosomal DNA of Serratia marcescens. The cloned fragment conferred increased resistance against UV and mitomycin C (MC) to ssb- mutants of Escherichia coli. The nucleotide (nt) sequence revealed that SSB consists of 175 amino acids (aa) and has an M(r) of 18,677. It shows 89% aa sequence homology with the SSB of E. coli. The nt sequence preceding the gene contains three promoters. Two of them overlap with a presumptive SOS box, and the distal one overlaps with a second SOS box that coincides with the promoter of the adjacent uvrA (gene encoding the UvrA protein). The uvrA is transcribed in a direction opposite to that of ssb. The sequence coding for the N terminus of the UvrA of S. marcescens indicates that the first 74 aa are identical to those of the E. coli protein. The results suggest that the two bacterial SSBs are members of a group which differs from the known SSBs of prokaryotic transmissible plasmids, because their aa sequence homology with these proteins is only about 60%. PMID- 8486287 TI - Cloning and sequencing the recA+ genes of Acetobacter polyoxogenes and Acetobacter aceti: construction of recA- mutants of by transformation-mediated gene replacement. AB - The recA+ gene of Acetobacter polyoxogenes was cloned as a gene that conferred methyl methanesulfonate resistance (MMSR) on the RecA- Escherichia coli HB101. The cloned recA+ gene also conferred (i) resistance to UV irradiation, (ii) enhanced intrachromosomal recombination, and (iii) permitted prophage phi 80 induction in E. coli recA- lysogens. Nucleotide sequence determination revealed that the recA product consists of 348 amino acids (aa) corresponding to 38 kDa, and shows significant similarity to RecA proteins from other Gram- bacteria. Next, a portion of recA from Acetobacter aceti was cloned by using polymerase chain reaction with oligodeoxyribonucleotide primers design based on the A. polyoxogenes recA sequence. Due to availability of efficient host-vector and transformation systems in A. aceti, recA mutants of A. aceti were obtained by transformation-mediated gene replacement with the cloned A. aceti recA gene which was inactivated by insertion of the kanamycin-resistance-encoding gene from pACYC177. The recA mutants obtained in this way showed similar phenotypes to those of E. coli recA strains, such as increased sensitivity to MMS and to UV irradiation, and decreased homologous recombination. PMID- 8486289 TI - Analysis of the self-defense gene (fmrO) of a fortimicin A (astromicin) producer, Micromonospora olivasterospora: comparison with other aminoglycoside-resistance encoding genes. AB - The nucleotide (nt) sequence of a 3409-bp PvuII fragment carrying the self defense gene (fmrO) of a fortimicin A (FmA; astromicin) producer, Micromonospora olivasterospora, was determined; four open reading frames (ORFs) exist in this region. Expression analysis of fmrO using the lac promoter in Escherichia coli revealed that ORF-3 encodes fmrO. ORF-1 was considered to encode a FmKH epimerase (fms11). ORF-2, ORF-3 and ORF-4 seemed to form an operon. No homology was detected between fmrO and the resistance-encoding gene fmrT of Streptomyces tenjimariensis, a producer of the Fm-group antibiotic, istamycin. Gene organization around the fmr genes differed considerably between M. olivasterospora and S. tenjimariensis. The deduced amino acid sequence of fmrO showed an identity of 30.8% to grmA of M. purpurea and 35.8% to grmB of M. rosea, respectively, suggesting that fmrO encodes a 16S rRNA methyltransferase. We found in M. purpurea a novel resistance gene distinct from grmA and highly similar to fmrO which conferred a resistance phenotype similar to that of fmrO. These results suggest that fmrO of M. olivasterospora and the two resistance-encoding genes of M. purpurea were derived from a common ancestral gene. PMID- 8486288 TI - The Azotobacter chroococcum hydrogenase gene cluster: sequences and genetic analysis of four accessory genes, hupA, hupB, hupY and hupC. AB - The Azotobacter chroococcum chromosome contains a region spanning about 14 kb associated with hydrogen-uptake (Hup) activity. The small and large subunits of the hydrogenase are encoded by the structural genes hupS and hupL. Two other genes, hupD and hupE, are located 8.9 kb downstream from hupL and are required for the formation of a catalytically active hydrogenase. In this study, we determined the nucleotide sequence of a 3.8-kb region immediately upstream from hupD. This revealed four additional closely linked ORFs which we designated hupA, hupB, hupY and hupC; these genes potentially encode polypeptides with predicted masses of 12.6, 33.3, 80.4 and 9.0 kDa, respectively. This cluster of genes was shown to be essential for hydrogenase activity by insertion mutagenesis using antibiotic-resistance gene cassettes and a Tn5 derivative carrying a promoterless lacZ gene. A 10.5-kb fragment of DNA beginning 3.4 kb downstream from hupL, and including the sequenced region, was able to complement hupA and hupY mutants, supporting earlier evidence for a promoter downstream from hupSL. The deduced amino acid sequences of hupA, hupB and hupC are homologous to the Escherichia coli hypA, hypB and hypC gene products, respectively. Of particular interest is the fact that there is no homologue of the hupY gene product in the E. coli hyp operon. Mutations in hupY or hupB had little effect on beta-galactosidase activity in a strain also carrying a hupL::lacZ fusion, showing that hupY and hupB are not major factors in regulating the transcription of the hydrogenase structural genes. PMID- 8486290 TI - Genes encoding eleven subunits of photosystem I from the thermophilic cyanobacterium Synechococcus sp. AB - We have isolated the genes encoding 11 photosystem I (PSI) subunits from Synechococcus sp., from which this reaction center has been crystallized. The recombinant DNAs, including psaA, psaB, psaC, psaD, psaE, psaF, psaI, psaJ, psaK and psaL, were obtained by heterologous hybridization with probes from appropriate cDNAs or genes from spinach and Synechocystis sp. PCC 6803, or with synthetic oligodeoxyribonucleotides. Genes psaA/psaB, psaF/psaJ and psaL/psaI are each closely linked. The open reading frames predict polypeptides of 83 kDa (subunits Ia and Ib, encoded by genes psaA and psaB, respectively), 15.4 kDa (II, psaD), 17.7 kDa (III, psaF), 8.4 kDa (IV, psaE), 8.8 kDa (VII, psaC), 4.6 kDa (VIII, psaI), 4.8 kDa (IX, psaJ), 8.5 kDa (X, psaK) and 15.5 kDa (XI, psaL). A novel subunit (XII, psaM) was also identified. Subunits II, III, IV and VII seem to be peripheral, while the others seem to be intrinsic components of the reaction center. These data imply a striking similarity of cyanobacterial and eukaryotic PSI. All subunits studied are encoded by single-copy genes which seem to be transcribed into monocistronic (psaC, psaD, psaC, psaK) or dicistronic (psaA/psaB, psaF/psaJ, psaL/psaI) RNA species. Subunit III is translated as a 17.7-kDa precursor, including a transit peptide of 23 amino acid residues. This is consistent with its location in the thylakoid lumen. PMID- 8486291 TI - Identification of a putative infC-rpmI-rplT operon flanked by long inverted repeats in Mycoplasma fermentans (incognitus strain). AB - A specific 1542-bp DNA fragment was amplified from Mycoplasma fermentans (incognitus strain) using a unique 23-nucleotide (nt) synthetic deoxyribonucleotide (oligo) (5'-TCCAAAAAGTCCGGAATTTGGGG) as the primer pair in the polymerase chain reaction (PCR). The 23-nt sequence is part of the 29-bp terminal inverted repeat (IR) which forms the left potential stem-and-loop (s&l) structure of the previously identified M. fermentans insertion-sequence(IS)-like genetic element [Hu et al., Gene 93 (1990) 67-72]. The amplified DNA was cloned and sequenced. A pair of 27-bp IR containing the 23-nt synthetic oligo was identified at both termini. Between the IR, there are four potential open reading frames (ORFs) which are arranged adjacent to each other in the order, ORF-1, ORF 2, ORF-3 and ORF-4, with parts of ORF-1 and ORF-2 overlapping. The deduced amino acid (aa) sequences of ORF-2, ORF-3 and ORF-4 are 34 to 60% identical to the translation initiation factor IF3 (encoded by the infC gene), ribosomal proteins L35 (rpmI gene) and L20 (rplT gene) of Escherichia coli and Bacillus stearothermophilus, respectively. In bacteria, the infC-rpmI-rplT genes are organized to function as an operon. There are multiple sites with promoter-like sequences identified upstream from the putative infC gene in the mycoplasma closely resembling the gene arrangement in the bacterial operon. All three genes of ORF-2, ORF-3 and ORF-4 are preceded individually by a strong appropriately spaced (7 and 10 bp) putative Shine-Dalgarno sequence (5'-AAGGA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486292 TI - A new cloning vector and expression strategy for genes encoding proteins toxic to Escherichia coli. AB - Here, we describe a modification of a plasmid, pT7-7 [Tabor and Richardson, Proc. Natl. Acad. Sci. USA 262 (1985) 1074-1078], that allows expression of inserted genes from the phage T7 RNA polymerase promoter. The modification is designed to suppress readthrough transcription from cryptic promoters and start points on the plasmid, in order to reduce expression in the absence of T7 RNA polymerase and thus improve the vector for use in the expression of highly toxic gene products. This vector (pT7SC) was used to stably clone the POL3 gene (encoding DNA polymerase delta) of Saccharomyces cerevisiae, which destabilizes all other cloning and expression vectors tested. Previously described expression strategies proved ineffective in overexpressing the POL3 gene. A new strategy was developed which relies on induction by infection with mutant T7 phage. This system efficiently overproduced the POL3 gene product. PMID- 8486293 TI - Final passages: physician-assisted dying. PMID- 8486294 TI - Assessing older drivers for physical and cognitive impairment. AB - For older drivers, the automobile is often a vital link in maintaining independence, acquiring goods, and socializing. However, physical or cognitive impairments linked to aging or disease may imperil the driver, passengers, and others on the road. For drivers with multiple medical conditions, physicians can reduce the risk for a crash by identifying and treating illnesses that can impair driving ability. If the conditions cannot be treated, consider modifying the driving environment to reduce the risk, rather than taking away driving privileges. If the risk is unacceptable, seek alternate modes of transportation. PMID- 8486295 TI - Seizure disorders of aging: differential diagnosis and patient management. AB - The incidence of seizures increases significantly after age 60, mainly because of an associated rise in the prevalence of such etiologies as stroke, brain tumors, and toxic-metabolic disturbances, including alcohol or drug misuse and diabetes. The differential diagnosis must rule out transient ischemic attacks, syncope, and psychiatric disorders, among other conditions. Treatment is based on the underlying cause. Seizures caused by toxic-metabolic disturbances are treated by correcting the underlying condition. Those with other etiologies require single drug therapy with an anticonvulsant, such as phenytoin, valproic acid, or carbamazepine. PMID- 8486296 TI - Exercise and aging: extending independence in older adults. AB - Exercise plays an important role in enhancing the quality of life of the older patient, although studies have shown that regular physical activity does not significantly lengthen life expectancy. Improved physiologic and psychological function helps to maintain personal independence and reduces demands for acute and chronic care services. This has significant economic benefits, as the resultant cost savings will likely cover the costs of a well-designed exercise program. Primary care physicians can help older patients to realize these benefits by encouraging them to increase their physical activity and by prescribing appropriate exercise regimens. PMID- 8486297 TI - Fernando Torres-Gil: Clinton's choice for top aging post. PMID- 8486298 TI - Enhancing independence in the older hip fracture patient. AB - No doubt all experienced clinicians have observed cases in which a hip fracture dramatically diminished the independence and quality of life of an elderly person. This difficult problem requires a concentrated, multidisciplinary effort. More than 800 patients have now been treated using our interdisciplinary approach. A recent review of the data shows that results in this larger group compare favorably with those in the followup group described in this article. We believe that our approach shows promise as a model for the future. Further, comparisons with current practices may lead in some situations to significant improvements in hip fracture rehabilitation. Primary care physicians play a key role in this process of review and modification and in contributing to the overall restorative effort. PMID- 8486299 TI - Laser scanning tomography and stereophotogrammetry in three-dimensional optic disc analysis. AB - Laser scanning tomography (LST) and computed stereophotogrammetry (CSP) are sophisticated diagnostic tools for the three-dimensional analysis of optic nerve head topography. The two methods are based on different physical principles. To compare the information about the shape of the cup of an optic nerve head obtained by LST and CSP, we evaluated the volume profile (VP; i.e., the cross sectional area of the cup from top to bottom) in 36 discs of 36 patients (20 control group discs C, 16 glaucoma discs G). The Spearman correlation coefficient between the photogrammetric and the laser scanning VP-slope measurements was rs = 0.931; P < 0.001 (rs = 0.935 G, P < 0.001; rs = 0.910 C, P < 0.001). The results suggest that confocal laser scanning provides readings of the shape of the optic disc cup that are similar to the measurements of computed stereophotogrammetry. PMID- 8486300 TI - Stereoscopic cooperation between the fovea of one eye and the periphery of the other eye at large disparities. Implications for anomalous retinal correspondence in strabismus. AB - In normal human observers we searched for the largest amount of visual disparity that can still provide depth information; we compared (1) crossed and uncrossed disparities and (2) symmetrical and asymmetrical locations of disparate stimuli. A pair of 3 degrees discs projected for 100 ms served as targets. Symmetrical stimuli were projected on temporal or nasal retinal loci in both eyes; asymmetrical stimuli were projected on the fovea of one eye and on the nasal or temporal periphery of the other eye. Thresholds were determined using a two alternative forced choice procedure. Subjects had to distinguish binocular disparate images from monocular double images of identical angular separation. Among six subjects, crossed disparities were recognized by one up to 6 degrees, by three up to 9 degrees, by one up to 18 degrees, and by one up to 21 degrees. Uncrossed disparities were recognized by two at 3 degrees, by two up to 6 degrees and by two up to 9 degrees. Hence, crossed disparities could be recognized up to higher angles than uncrossed. No consistent difference was found between symmetrical and asymmetrical stimuli. Stimuli with crossed disparity appeared smaller and with uncrossed disparity larger than monocular stimuli of the same objective size, suggesting that the size-constancy mechanism operates when disparity stimuli are presented as briefly as 100 ms, i.e., without simultaneous vergence eye movements. We speculate that the far-reaching interocular connections demonstrated in normal subjects might also be utilized in the case of strabismus: these interocular connections could form the basis for anomalous retinal correspondence. PMID- 8486302 TI - Survival prognosis of patients with retinal artery occlusion and associated carotid artery disease. AB - The records of 151 patients who developed retinal arterial obstruction were reviewed to evaluate the survival prognosis of these patients. Survival rates were calculated to expected rates of an age- and sex-matched control group of patients without retinal arterial obstruction. The presence of visible embolus and a branch retinal artery occlusion were found to be significant factors for worse survival prognosis (P = 0.0001 and P = 0.001, respectively). The survival rate of the entire group of 151 patients with retinal artery occlusion was not significantly different from that of the age- and sex-matched group (P = 0.29). Among the patients evaluated with continuous-wave Doppler sonography, the presence or the absence of the atheromatous carotid disease did not significantly affect the survival. PMID- 8486301 TI - Visibility of the normal retinal nerve fiber layer correlated with rim width and vessel caliber. AB - Since the distribution of the retinal nerve fiber layer (RNFL) is not regular, this study was performed to evaluate the normal regional variation in its ophthalmoscopic appearance. Wide-angle red-free photographs of the RNFL and color stereo optic disc slides of 195 normal eyes of 119 subjects were morphometrically examined. The RNFL was most visible in the temporal inferior sector, with the neuroretinal rim being correspondingly broadest (P < 0.001) and the diameter of the corresponding retinal artery the widest; these parameters were found to diminish appreciably in the temporal superior sector, the nasal superior sector, and the nasal inferior sector in this order. The visibility of the RNFL in a particular region therefore correlates positively with the rim width and retinal artery caliber in that region, the RNFL being most detectable in the temporal inferior part of the fundus. This may be important in the evaluation of eyes with optic nerve damage. PMID- 8486303 TI - Fetal development of the human orbit. AB - The development of the orbits in 70 human fetal skulls was investigated by measuring the width and height of the orbital entrance, as well as the volume and depth of the orbital cavity and the interorbital width. For determination of the orbital volume, we used the imprint method; the remaining parameters were estimated. Our measurements showed a linear growth rate for the orbital width, height, and depth. After transformation to the cubic root, the values of the orbital volume also demonstrated a linear increase. The orbital index (height/width x 100) expressed the change in the oval outline of the orbital entrance during fetal development from a flat, wide form to a nearly round form at birth. No statistically significant difference between the right and left orbit was found. PMID- 8486304 TI - Ascorbic acid phosphate ester and wound healing in rabbit corneal alkali burns: epithelial basement membrane and stroma. AB - We examined the effect of L-ascorbic acid 2-phosphate (P-Asc) on the healing of alkali-burned corneas in rabbits. Round filter paper containing 1 N NaOH was applied to the central cornea for 60 or 120 s to produce the alkali burn. Animals were treated with topical saline, 10% ascorbate, or 6.5% P-Asc applied on the cornea. The corneas were then examined histologically. Burned stroma showed no toluidine blue staining, indicating a loss of glycosaminoglycan. In the 60-s burn group, P-Asc reduced the size of the unstained area as compared with the control. Transmission electron microscopy showed basal lamina under new epithelia in the corneas treated with ascorbate or P-Asc, but not in controls. These observations support the theory that P-Asc may have a therapeutic role in the repair of corneal alkali burns. PMID- 8486306 TI - Retinal detachment and degeneration in response to subretinal perfluorodecalin in rabbit eyes. AB - Perfluorocarbon liquids, including perfluorodecalin (PFD), are useful intraoperative tools in complicated vitreoretinal surgery, such as for giant retinal tears, PVR and intraocular foreign bodies. Due to its high specific gravity (1.91 g/cm3) subretinal complications of PFD may occur. The consequences of subretinal PFD were studied in 23 albino rabbits (28 eyes). Using glass micropipettes (outer diameter of tip 100-120 microns), we injected 50-100 microliters PFD subretinally via the vitreous space. The same volume of BSS was injected into 18 control eyes. Eyes were monitored by indirect ophthalmoscopy and examined by light and electron microscopy at 1, 2 and 3 days, and 1, 2, 4 and 12 weeks. Progressive retinal detachments with newly formed retinal breaks in the inferior quadrants developed in 26 of 28 eyes. As early as 1 day postoperatively, subretinal PFD induced loss of outer and inner segments. Local retinal necrosis occurred in 4 eyes 5-7 days after surgery. A marked vacuole formation in retinal layers and PFD emulsification were regularly seen. The control eyes healed spontaneously. Toxic, mechanical and barrier effects may have caused the retinal damage. We advocate that all PFD be removed from the eye at surgery. PMID- 8486305 TI - Distribution of epidermal growth factor in rat ocular and periocular tissues. AB - Using a sensitive radioimmunoassay (RIA) specific for rat epidermal growth factor (rEGF), we investigated the presence of rEGF in a variety of rat ocular and periocular tissues. Immunoreactive rEGF (IR-rEGF) was present in tear fluids (25.5 +/- 5.8 ng/ml), exorbital lacrimal gland (6.73 ng/g wet weight), intraorbital lacrimal gland (2.80 ng/g wet weight), Harderian gland (1.90 ng/g wet weight), and conjunctiva (0.16 ng/g wet weight). EGF was not detectable in aqueous humor, cornea, iris and ciliary body, lens, or the posterior part of the globe (retina, choroid, and vitreous body). Gel exclusion chromatography and reverse-phase high-performance liquid chromatography revealed that IR-rEGF in the above ocular fluids and tissues was indistinguishable from standard rEGF. Using enzyme-linked immunohistochemistry, rEGF was demonstrated to be localized in the duct epithelial cells of lacrimal glands. These findings reveal that EGF is preferentially localized in the ocular surface and lacrimal apparatus. PMID- 8486307 TI - Immunological reactions against PMMA lens material? AB - We investigated the kind of reactions that occur after injection of a PMMA lens powder into the back skin of rabbit. The lens powder was suspended in NaCl and incomplete Freund's adjuvant to reinforce the immunological reaction. The ELISA test was carried out to detect antibodies against the lens material as a whole and against the UV absorber Tinuvin in particular. We also performed histological and immunohistochemical examinations of the back skin. We did not detect antibodies against either the lens material or against Tinuvin. Histological examination showed a foreign-body or delayed allergic reaction against the lens material. Lymphocytes surrounding the PMMA were found to be mainly of the T-type, which supports the results of the ELISA test. PMID- 8486308 TI - Senior-Loken syndrome with marbelized fundus and unusual skeletal abnormalities. A case report. PMID- 8486309 TI - Invasive squamous cell carcinoma of the palpebral conjunctiva. PMID- 8486310 TI - [A portrait of Dr. Enrique Gutierrez Murillo]. PMID- 8486311 TI - [Hepatitis C during puerperium]. AB - Screening of donor blood for hepatitis B led to recognition that most cases of post-transfusion hepatitis were due to an agent known as non-A, non-B. Until recently the causative agent for non-A, non-B hepatitis was identified, being denominated hepatitis C virus. It is estimated that one-half of patient with hepatitis C develop chronic liver disease, and 20% of this will develop cirrhosis. We describe a patient who due to obstetric complications received blood transfusion and during puerperium developed an icteric syndrome which was identified as C hepatitis. We review the diagnostic methodology, clinical characteristics, evolution and preventive measures of the C hepatitis. PMID- 8486312 TI - [The role of estradiol and progesterone receptors in the selection of endocrine therapy fo patients with fibrocystic mastopathy]. AB - Estradiol and progesterone receptors were analyzed in breast tissue of 100 women with mastopathy fibrocystic. Four groups were found according to the receptors detected: (R-E+, R-Pg+); (R-E+, R-Pg-); (R-E-; R-Pg+); (R-E-, R-Pg-). Ten percent were positive for both receptors, while 75 percent were negative for both estradiol and progesterone receptors. Ten percent were estradiol receptor positive (R-E+). Eight percent were progesterone receptor positive (R-Pg+). In this pathology type were considered "receptor positive" when specific binding was higher than 6 fmol/mg. protein. These "receptor positive" had specific binding in the range of 6.1-80 fmol/mg. protein and was considered "receptor negative" when specific binding was less than 6 fmol/mg. protein. While there was no correlation between the two receptors and patient age. We discuss the presence, type of estradiol and progesterone receptors for the hormonal treatment of patients with mastopathy fibrocystic. PMID- 8486313 TI - [Radioactive antiestrogens: their clinical use]. AB - Using antiestrogen labelled with iodine-131 we proved the useful as diagnostic and therapeutic tools to identified hormone dependent cancers in breast with very encorageous results in 7 cases of human cancer. The method was simple and safe and similar methods for scanning of prostate tumors dependent are in current research in our laboratory and will be object of other communications. PMID- 8486314 TI - [Index of cells obtainable from semen: indicator of fertility?]. AB - It has been recognized that semen analysis is not a sensible nor a specific tool for detecting infertility in the male. Its predictive value is limited by the subjectivity of manual analysis, a high variability of semen parameters in fertile men and lack of correlation between sperm characteristics and fertility indexes. In this paper we present evidence supporting the concept that calculating an index of potentially fertile cells from data obtained in a regular semen analysis might be useful for predicting fertility in the male. PMID- 8486315 TI - [Obtaining zona-free ova from the golden hamster (Mesocricetus auratus Waterhouse)]. AB - Our methodology for obtaining zona-free ova from golden hamster females (Mesocricetus Auratus Waterhouse) is described here. Five groups of 5 females were superovulated injecting intraperitoneally pregnant mare gonadothropins (PMG) at different dosages. The control group received 0.25 ml of distilled water. We harvested 653 ova from the stimulated females with an average of 32.65 per individual (range 16-52). The control group produced a total of 50 ova with an average of 10 (range 0-14). PMG optimum dose was 25 IU with an average of 39 (S.D. +/- 10.93) (n = 195 ova). The best conditions for denuding the cumulus was a 0.01% hyaluronidase solution with an average time of 10 minutes (S.D. +/- 03'56"). The optimum conditions for digesting the zona was 0.20% trypsin during 03'20" (S.D. +/- 01'19"). The proof that the ova were not damaged by the procedure was by means of a supravital stain (Eosin Y). All mature ova (N = 681) were not affected by enzymes or manipulation. Final preparation used a 1% acetic acid fixation and staining with 0.01% methylene blue, both acting for 1-3 minutes. Animal gametes give us the opportunity to substitute human ova in biology of reproduction studies and experiments, avoiding technical, ethical and moral problems. PMID- 8486317 TI - [Proceedings of the regional meetings of the Italian Society of Hematology]. PMID- 8486316 TI - [Attitudes and behavior for reproductive health]. AB - Educational interventions represent an alternative for the reproductive well being. The objective of this investigation was to identify in a mexican community, attitudes and behaviors related to reproductive health, with the goal of implementing a specific health education program. The study population consisted of women between 12 and 44 years old, living in non-residential areas of the Delegation Miguel Hidalgo, D.F. Variables of interest were analyzed only in women with parity (n = 300). Data were collected through interview. The mean age was 31 +/- 8 years. 93.3% were married or in consensual union. 63% had elementary, junior high or prevocational studies. 89% answered that would visit the doctor before considering a pregnancy (junior high+, p < .05), 99% would seek prenatal care if they were pregnant, and 92.7% would have a hospital delivery (parity < or = 3, p < .003). 69.5% had a preconceptional visit before their last pregnancy and 89.9% received prenatal care (junior high+, p < .008). 92.5% had only hospital deliveries (< or = 30 years, p < .05, junior high+, p < .0001, primigravida p < .002, with institutionalized medical services, p < .001), 1.7% had only out-of-hospital deliveries, and 5.8% both. Agreement between attitudes and behaviors are presented. An educational program consisting of confirmation and support to positive attitudes, values and beliefs, and reinforcement to decision making, will result in a final behavior: early assistance to medical care. PMID- 8486318 TI - [Isolation, configuration and contractile responses of single smooth muscle cells]. AB - In studies on the intrinsic contraction mechanisms of smooth muscle, various factors such as cell-to-cell interaction, penetration of chemicals to the trigger regions, or extracellular spaces in the tissue may influence the results. The use of single smooth muscle cells in such investigations may help to eliminate these factors. Single smooth muscle cells can be isolated from guinea pig taenia coli by digesting the minced tissue with a combination of collagenase and soybean trypsin inhibitor. The cells are spindle shaped, 100-200 microns in length and 10 microns in diameter. Three kinds of techniques for determination of contractile responses of single smooth muscle cells have been established: 1) fixation method, 2) perfusion method, and 3) capillary adhesion method. Using these techniques, the cells appeared to be contracted in a dose-dependent manner (graded response), while another mode of the contractile response, the "all-or none response", has also been proposed. Scanning and transmission electron micrographs of the single cells revealed several evaginations of various sizes and shapes on the surface and electron dense bodies at the neck of the evaginations. ED50 obtained with the single cells, prepared from taenia coli of guinea pigs with collagenase in the presence of trypsin inhibitor was similar to that obtained with the intact tissue. Digestion of the tissue with highly purified collagenase and papain yields a large number of single cells with higher sensitivity to agonists. Characteristics of cells isolated from ileal longitudinal muscle of guinea pig are similar to those of cells isolated from taenia coli. The magnitude of contraction and sensitivity to acetylcholine were different in each cell. Incubation of isolated tissues with various concentrations of agonists followed by measurement of cell length in the tissue showed that the heterogeneous responses of the cells were intrinsic characteristics of smooth muscle cells and not due to damage incurred during the isolation procedure. Since isolated smooth muscle cells possess contractility, these might preserve the characteristics of smooth muscle, so they can be used for smooth muscle research. It must be considered, however, that each cell in the smooth muscle tissue has different contractility. PMID- 8486319 TI - [All-or-none response of isolated smooth muscle cells from guinea pig taenia caecum to acetylcholine]. AB - Most isolated smooth muscle cells from guinea pig taenia caecum responded repeatedly, showing an all-or-none response to acetylcholine (ACh). However, the average responses of all the cells were graded owing to the difference in the threshold concentration of ACh, like that of whole tissue. The sensitivity of the muscarinic receptor on individual cells was the same as that of whole tissue and ACh bound to the receptor concentration-dependently. The shortening of the cells in response to ACh depended upon the influx of extracellular Ca2+ through the Ca channel. 45Ca2+ influx stimulated by ACh was very sharp and highly correlated with the shortening of the cells. The shortening of alpha-toxin-permeabilized smooth muscle cells was induced by increasing free Ca2+. The concentration response relationship to free Ca2+ had a very steep slope, and the shortening appeared to be an all-or-none response rather than a graded response. In conclusion, it is suggested that isolated smooth muscle cells show an all-or-none response as a result of a slight increase in the intracellular free Ca2+ level over the threshold concentration when early signalling coupled to ACh-receptor stimulation reaches the threshold to evoke Ca2+ influx and Ca2+ release. PMID- 8486320 TI - [Ca2+ release mechanism studied in single isolated smooth muscle cells]. AB - This paper briefly reviews our current effort to study the Ca2+ mobilization mechanism in enzymatically dispersed single smooth muscle cells. Each single cell obtained from guinea pig taenia caeci possesses two types of Ca2+ stores, one (S alpha) with both Ca(2+)-induced and IP3-induced Ca2+ release mechanisms and the other (S beta) with only IP3-induced Ca2+ release mechanism. After depletion of S alpha either with ryanodine treatment or with caffeine pretreatment, carbachol failed to induce Ca2+ release, while intracellular application of IP3 did induce Ca2+ release. Our results suggest that the difference between the agonist- and IP3-induced responses can be resolved by obligatory involvement of positive feedback control of IP3-induced Ca2+ release in the agonist-induced Ca2+ release. Furthermore, we were able to demonstrate that the dose-response relation in single cells shows an all-or-none feature, which seems at least partly due to the feedback control of Ca2+ release. We discuss the reasons why graded dose-response relation is obtained in bundles of smooth muscles, while the response of single cells is an all-or-none type. PMID- 8486321 TI - [Pharmacological studies on antidiarrheal effects of a preparation containing berberine and geranii herba]. AB - We studied the effects of a preparation containing Berberine and Geranii Herba (BGH) on different diarrheal models of mice and the contractions of isolated guinea pig intestinal smooth muscle, comparing these effects with those of a preparation containing creosote (CSG) and loperamide (LP). BGH, as well as CSG and LP, significantly inhibited the diarrhea induced by castor oil or BaCl2, but not the diarrhea induced by pilocarpine or serotonin. BGH inhibited ACh-, Ba(2+)- or electrical stimulation (ES)-induced contraction of the ileum or colon at concentrations from 10(-6) to 10(-4) g/ml. On the other hand, the inhibitory effect of CSG on the ES-induced contraction was about one hundred times stronger than that on ACh- or Ba(2+)-induced contraction. The order of the inhibitory potency of LP on contractions of the ileum in this test was ES > Ba2+ > ACh, and LP showed stronger inhibition against the contraction of the ileum than that of the colon. These results suggest that BGH exerts its antidiarrheal action by inhibiting intestinal movement, and the mechanism of action of BGH may differ from those of CSG or LP. PMID- 8486322 TI - [Effects of NC-1100, a calcium channel blocker, on experimental cerebral ischemia/anoxia in rodents]. AB - The anti-ischemic and anoxic effects of NC-1100, a piperazine type calcium channel blocker, were investigated in various cerebral ischemia and anoxia models in mice, gerbils and guinea pigs. Minimal effective doses of NC-1100 were 8 mg/kg, i.p. and 30 mg/kg, p.o. for KCN-induced anoxia; 16 mg/kg, i.p. for decapitation-induced gasping; 30 mg/kg, i.p. for cerebral ischemia induced by occlusion of bilateral carotid arteries in gerbils; and 10 microM for the in vitro ischemic model in hippocampal slices. Moreover, NC-1100 attenuated the disturbance of cerebral energy metabolism induced by decapitation in mice. These results suggest that NC-1100 has a cerebral protective effect, and that attributable to its ability to improve the cerebral energy metabolism disturbance. PMID- 8486323 TI - [The role of the central monoaminergic nervous system relative to mechanisms of stress adaptation]. AB - The difference of amine dynamics in central noradrenergic, dopaminergic and serotonergic systems of adaptive or non-adaptive rats to repeated restraint stress was investigated neurochemically. A single immobilization induced stress responses, such as reductions in growth rate, food intake, water intake and locomotor activity, and an increase in pain threshold. These responses disappeared after repeated immobilization 1 or 2 hr daily for 7 days, but not after 4 hr daily for 7 days. These results suggest that stress adaptation models should include the parameter of repeated exposure to restraint stress 1 or 2 hr daily for 7 days. In the frontal cortex, midbrain-thalamus, striatum, hypothalamus, medulla-pons, cerebellum, cervical cord, thoracic cord and lumbar cord of models with adaptability to repeated restraint stress, a marked increase in serotonin (5-HT) turnover was observed. This neurochemical change was seen in the hypothalamus and lumbar cord of non-adaptive models, but not in the other brain and spinal cord regions. Also, an increase in norepinephrine (NE) turnover in spinal cord regions was observed in adaptive models, but NE turnover was decreased in the frontal cortex, striatum or cervical cord of non-adaptive models. These findings suggest that enhancement of central 5-HT turnover and NE turnover in the spinal cord contribute to the formation of adaptation to repeated restraint stress. PMID- 8486324 TI - [Liver transplantation as a routine procedure? Indications and results in 270 patients]. AB - AIM: To represent the current state of the art of orthotopic liver transplantation (OLT). The constantly expanding spectrum of indications are discussed in detail, and the specific risks of the individual indications considered. Major points discussed: On the basis of the authors' own results obtained at the Rudolf Virchow Hospital, University of Berlin, the current survival rates following orthotopic liver transplantation are shown. In addition to established indications for liver transplantation (primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, various metabolic diseases, small hepatocellular carcinomas and a number of posthepatic cirrhoses) the indication and results of liver transplantation in HbsAg-positive and alcoholic cirrhosis are presented in detail. In contrast to reports in the Anglo American literature, the incidence and severity of graft re-infections with the hepatitis virus was appreciably reduced through the use of anti-HBs hyperimmunoglobulin preparations in HBsAg-positive cirrhotics. The results obtained were comparable with those achieved for other indications. PMID- 8486325 TI - [Cytokine activity. On key substances of intercellular signal transduction]. PMID- 8486326 TI - [Rational therapeutic strategies in onychomycoses. When topical, when systemic treatment?]. PMID- 8486327 TI - [New guidelines for fracture treatment. Part 9: Ambulatory after-care--follow-up, complications]. PMID- 8486328 TI - [Prevention of traveler's diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study]. AB - BASIC REMARKS: Among travellers to distant countries with a low socioeconomic status and poor hygiene, traveller's diarrhea is a major problem. Once this epidemiological fact had been recognized, intensive efforts were made to reduce the incidence of this illness by prophylactic medication. Among non-antibiotic substances investigated, Saccharomyces boulardii (SB) appeared to show promising results in earlier studies. METHOD: In a placebo-controlled, double-blind study, various dosages (250 mg and 1,000 mg SB) were administered prophylactically to 3,000 Austrian travellers to distant regions. RESULTS: A significant reduction in the incidence of diarrhea was observed, with success depending directly on the rigorous use of the preparation. A tendency was noted for SB to have a varying regional effect, which was particularly marked in North Africa and in the Near east (Turkey!); in addition, the effect also proved to be dose-dependent. The medication can be classified as low on side effects. PMID- 8486329 TI - A microcomputer program to determine the precision of elimination rate constant and half-life estimates when sampling time is short. AB - First-order elimination of drugs is often assumed in pharmacokinetics and elimination rate constant is then frequently determined by log-linear regression analysis from plasma concentration measurements. When the time which elapses between the first and the last plasma sample is short compared to the decay half life, the elimination rate constant may not be determined with satisfactory precision, in particular because of analytical error. Application of basic principles of linear regression analysis allowed us to quantify the theoretical effect of analytical error on the determination of the drug elimination rate constant in that situation. It was highlighted that the precision of that determination could be efficiently improved by measuring samples in replicate, which should be recommended in practice. A user-friendly program was developed which can be used prospectively to optimize sampling strategy, and retrospectively to estimate the precision of parameter estimates. The program works on IBM PC and compatible microcomputers and is available on request. PMID- 8486330 TI - Neurotensin modulates differently potassium, veratridine and 4-aminopyridine evoked release of dopamine in rat striatal slices. AB - We have studied the effects of neurotensin (NT) on the release of [3H]dopamine ([3H]DA) evoked by terminal depolarization with either K+, veratridine or 4 aminopyridine (4-AP). NT (1-1000 nM) induced a net potentiation (up to 170%) of the K+ (25 mM)-evoked release of [3H]DA. The capacity of NT to potentiate the effect of K+ ions decreased as the K+ concentration rose from 25 to 50 mM and totally disappeared at this high K+ concentration. NT (100 nM; 1,000 nM) had no significant effect on the veratridine (1.5; 5 microM) or 4-AP (20 microM) -evoked release of [3H]DA. The relevance of these experimental models of DA release to physiological transmitter release remains to be established. Those data highlight the complexity of the modulation of evoked neurotransmitter release by pharmacological agents. PMID- 8486331 TI - Transient left bundle branch block following intravenous lisuride bolus. PMID- 8486332 TI - Identification of the human and animal hepatic cytochromes P450 involved in clonazepam metabolism. AB - This report characterizes the cytochrome P450 isozyme involved in clonazepam metabolism. This study was undertaken using a library of liver microsomal fractions prepared from untreated rabbits or those treated with drugs known to specifically induce various cytochrome P450 isozymes (ie P450 2B4 by phenobarbital, P450 1A1 and P450 1A2 by 3-methylcholanthrene and beta naphthoflavone, P450 2E1 by acetone and ethyl alcohol, and P450 3A6 by erythromycin). Only microsomes obtained from phenobarbital-treated rabbits exhibited a type II binding spectrum upon addition of clonazepam (Ks(app) = 31.4 +/- 3.8 microM) and significantly metabolized clonazepam to 7-aminoclonazepam. Benzphetamine, which is a known substrate for P450 2B1 was also extensively metabolized by microsomes prepared from phenobarbital treated rabbits. This indicates that the same isozyme (P450 2B subfamily) was involved in the biotransformation of both substrates. Experiments performed on 14 human liver microsomal preparations showed a wide interindividual variability (from 1-4) and a good correlation (r = 0.70) between benzphetamine and clonazepam metabolism. Since P450 3A4 (nf25) was involved in benzphetamine metabolism, clonazepam was probably nitroreduced by the same isozyme. An oligonucleotide specific for the P450 3A4 gene subfamily was synthetized and used for hybridization on total RNA from human liver samples. Two transcripts of 2.2 and 3.0 kb were detected and the level of the 2.2 kb mRNA expression was significantly correlated (r = 0.61) with the intensity of clonazepam nitroreduction by the corresponding microsome batches. PMID- 8486333 TI - Comparative evaluation of ulcer prevention efficacy of orally, rectally and sublingually administered omeprazole in three acute gastric ulcer models in rats. AB - Ulcer prevention efficacy of orally, rectally and sublingually administered omeprazole was evaluated and compared using ulcer index and percentage inhibition of ulcerogenicity in three different acute gastric ulcer models viz, indomethacin, 0.6N HCl and aspirin (after pylorus ligation) induced ulcers in rats. The ulcer prevention efficacy after oral, rectal and sublingual administration were statistically significant (P < 0.01) in all the models. The differences in ulcer index and percentage inhibition of ulcerogenicity for rectal and sublingual administration were insignificant (P < 0.05) in indomethacin and HCl induced ulcers and were significant (P < 0.05) in aspirin induced ulcers. The ulcer prevention activity was significantly higher (P < 0.05) after rectal and sublingual routes when compared to oral administration in all three models evaluated. Results revealed a faster onset and higher extent of pharmacodynamic activity of omeprazole after rectal and sublingual administration. PMID- 8486334 TI - Effects of capsaicin on the endothelial permeability in isolated and perfused rabbit lungs. AB - Changes in pulmonary endothelial permeability and in microvascular hemodynamics in response to capsaicin (10(-4) M) were investigated in isolated, perfused rabbit lungs. Blood-free perfusate was recirculated through ventilated lungs in an isogravimetric state, under zone III conditions with a constant flow. Using the occlusions method, the total pressure gradient between the arterial and the venous levels (delta Pt) was partitioned into four components: arterial (delta Pa), pre-(delta Pa') and post-(delta Pv') capillary, and venous (delta Pv). The capillary filtration coefficient (Kf,c) was evaluated by measuring the amount of fluid filtering through the endothelium when arterial and venous pressures were suddenly increased. Capsaicin caused no changes in the vascular pressures at any level of the pulmonary circulation but induced a significant 3-fold increase in the Kf,c (P < 0.05). This reaction was accompanied by pulmonary oedema. The mechanisms involved in the permeability changes were investigated by testing the capacity of different drugs to block the response to capsaicin. Clonidine (10(-7) M to 10(-5) M), morphine (10(-6) M), aspirin (10(-3) M), ketanserin (10(-8) M) and (+/)- CP 96,345 (10(-6) M), an antagonist of neurokinin NK1 receptor, completely prevented the effects of capsaicin on the Kf,c. In contrast, terfenadine (10(-7)) together with cimetidine (10(-5) M) had no protective effect against capsaicin. It was concluded that capsaicin-induced pulmonary oedema was due to an increase in the capillary filtration coefficient and not to hemodynamic changes. This alteration in the endothelium permeability is mediated by the release of endogenous peptides from C-fibers upon the action of capsaicin and subsequent activation of NK1 receptors, probably by substance P. Moreover, 5 hydroxytryptamine receptors and arachidonic acid derivates are also involved in this reaction. PMID- 8486335 TI - International Meeting on the Therapy of Hematological Malignancies in the Elderly. Proceedings. Turin, 15-16 April 1993. PMID- 8486336 TI - Aggressive chemotherapy of ALL in elderly patients. PMID- 8486337 TI - Prognostic factors in myelodysplastic syndromes. PMID- 8486338 TI - Recent advances in the management of myelodysplastic syndromes. PMID- 8486339 TI - When and how to treat elderly patients with chronic lymphocytic leukemia (C.L.L.)? The French Cooperative Group on C.L.L. PMID- 8486340 TI - The management of elderly patients with myeloproliferative disorders. PMID- 8486341 TI - Is intensive treatment beneficial to elderly patients with ANLL? PMID- 8486342 TI - The Italian experience in the treatment of HCL. Italian Cooperative Group for HCL. PMID- 8486343 TI - The treatment of low grade non-Hodgkin's lymphoma in elderly people. PMID- 8486344 TI - Multiple myeloma: a tailored therapy for elderly patients. PMID- 8486345 TI - Hodgkin's disease of the elderly. A different disease? PMID- 8486346 TI - Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse. AB - Gene constellations on several human chromosomes are interpreted as indications of large regional duplications that took place during evolution of the vertebrate genome. Four groups of paralogous chromosomal regions in man and the house mouse are suggested and are believed to be conserved remnants of the two or three rounds of tetraploidization that are likely to have occurred during evolution of the vertebrates. The phenomenon of differential silencing of genes is described. The importance of conservation of linkage of particular genes is discussed in relation to genetic regulation and cell differentiation. PMID- 8486347 TI - A chromosome 13-specific human satellite I DNA subfamily with minor presence on chromosome 21: further studies on Robertsonian translocations. AB - We describe a new human satellite I DNA subfamily (pTRI-6) which is composed of 72 copies of monomeric repeating units of 42 basepairs (bp). These repeating units are tandemly organized into a higher order structure of 2.97 kilobases (kb). Sequencing of this DNA revealed base substitutions, deletions and insertions, and an overall conservation of 85% among the monomers. The sequence has a high AT content of 77%. Under low-stringency in situ hybridization conditions, satellite I is found on the pericentric regions of chromosomes 3 and 4 and on all the acrocentric chromosomes. On the acrocentric chromosomes, satellite I is further detected on the distal p13 region. Analysis of somatic cell hybrids under high stringency indicates the presence of the pTRI-6 subfamily predominantly on chromosome 13. Chromosome 21 shows a 50- to 100-fold reduced amount of this subfamily and the presence of other sequences closely related to pTRI-6. Investigation of a group of 11 human t(14q21q) Robertsonian translocations revealed the retention of satellite I DNA around the breakpoints in all cases. These results extend our understanding of these translocations and of the general structural organization of the cen-pter regions of the acrocentric chromosomes. PMID- 8486348 TI - Organization of the human CD9 gene. AB - The CD9 antigen was originally described as a 24-kDa molecule present on B lineage-derived acute lymphoblastic leukemia cells and developing B lymphocytes. Platelets also express a large amount of CD9 antigen and can be activated by CD9 antibodies. We report here the structure of the CD9 gene, which is composed of 8 exons spanning more than 20 kb. There is no TATA or CAAT box in the 5'-flanking domain of the CD9 gene, but a 120-bp region extremely rich in C and G (88%) contains several Sp 1 binding sites and a consensus site for the binding of zinc finger proteins of the Krox/EGR family. The CD9 antigen belongs to a new cell surface protein family. The organization of its gene closely resembles the organization of the genes for two other members of this protein family, TAPA1 and CD63, which share with CD9 respectively 45 and 25% identity at the amino acid level. PMID- 8486349 TI - A B2 repeat insertion generates alternate structures of the mouse muscle gamma phosphorylase kinase gene. AB - A variety of cDNA and genomic clones for the gamma-subunit of mouse muscle phosphorylase kinase (Phk-gamma M) have been isolated and characterized. The murine gene for Phk-gamma M (Phkg) exhibits multiple transcription start sites that are identical in skeletal muscle, cardiac muscle, and brain. The gene is composed of 10 exons and includes a 4.9-kb intron located in the 5' untranslated region. Two mRNA species of 1.75 and 2.55 kb are produced from Phkg in ICR and C57BL/10 mice; these transcripts are colinear throughout the coding region and differ only in the length of the 3' untranslated region. We have mapped the polyadenylation site of the 1.75-kb mRNA to the middle of exon 10; the 2.55-kb mRNA terminates further 3' at the end of a mouse B2 repeat. In Balb/C mice an additional B2 insertion and related genomic rearrangements alter the sequence of Phkg exon 10 and are accompanied by an increase in the quantity of the 1.75-kb transcript and a decrease in the abundance and size of the longer transcript, from 2.55 to 2.35 kb. A PCR assay for sequences contained in exon 10 reveals that the Balb/C 3' gene structure is shared by Mus musculus castaneus and Mus musculus molossinus; the C57BL/10 gene structure is shared by Mus spretus, Mus domesticus, and several strains of laboratory mice. These results suggest that Phkg in Balb/C mice was derived from M. m. molossinus and that Phkg of the other examined laboratory strains was derived from M. domesticus. PMID- 8486350 TI - The human glutamate dehydrogenase gene family: gene organization and structural characterization. AB - Glutamate dehydrogenase is a mitochondrially located, key metabolic enzyme. In addition to its general metabolic role, GLUD is important in neurotransmission. Significant alterations in GLUD enzymatic activity have been associated with certain neurodegenerative human disorders. Although a single species of human GLUD cDNA molecule has been identified so far, both genomic DNA Southern and cytogenetic analyses have indicated the presence of a GLUD gene family. Screening of a human genomic lambda-phage library with the GLUD cDNA, led us to the isolation of several clones divided into five structurally distinct contigs. We have confirmed the presence of all GLUD-specific sequences in the human genome by detailed genomic Southern analysis. This study allowed the identification of the entire functional GLUD gene, named GLUD1. The GLUD1 gene is about 45 kb long and it is organized into 13 exons. Its nucleotide sequence, exon-intron boundaries, and transcription start sites were determined. Potential binding sites for various regulatory factors such as Sp1, AP-1, and AP-2 were recognized at the promoter region of the gene. The members of the other contigs showed an organization clearly different from GLUD1. Two distinct GLUD-specific gene loci, termed GLUDP2 and GLUDP3, possibly represent truncated pseudogenes. Their high degree of similarity to GLUD1 is limited to the region surrounding exons 2, 3, and 4. Finally, two additional GLUD-specific genomic sequences, termed GLUDP4 and GLUDP5, are structurally similar with the 3' part of the GLUD cDNA sequence. These loci probably represent truncated GLUD pseudogenes generated by retrotransposition. The data presented here suggest that all human GLUD pseudogenes have diverged recently in evolution. PMID- 8486351 TI - The short 3'-end region of complementary DNAs as PCR-based polymorphic markers for an expression map of the mouse genome. AB - Ideal markers for a complementary DNA (cDNA) map of the mouse genome should be amplifiable by the polymerase chain reaction (PCR) and they should be polymorphic for genetic mapping, as well as unique for physical mapping. In our search for such markers, we did comparative sequencing of PCR-amplified genomic DNAs derived from 15 inbred strains and found that about 250 bp of the 3'-end region (3'-ER) of cDNAs, which is the sequence immediately upstream from the poly(A) tail, was polymorphic enough to distinguish the allele of a laboratory strain from that of a wild strain (Mus spretus) in 14 of 22 cDNAs tested. Specifically, in 9 of these 14 cDNAs, each allele was identified by the restriction fragment length polymorphism. This data indicates that about 65% of the 3'-ERs of cDNAs can be automatically transformed into PCR-based genetic markers named "biallelic polymorphic expressed sequence tags (bESTs)." These markers can be easily and precisely mapped by typing of the panels of interspecific backcrosses. Because a large number of bEST markers can be efficiently obtained by a single-run automated sequencing of randomly selected cDNAs, these markers will greatly facilitate the construction of high-resolution genetic and physical maps of expressed sequences of the mouse genome. PMID- 8486352 TI - Microdissection and microcloning of genomic DNA markers from human chromosomal region 11q23. AB - A human genomic DNA library was constructed by using a microdissection microcloning procedure with polymerase chain reaction (PCR) techniques on DNA from the chromosome 11q23 region. A total of 450 recombinant pUC clones were isolated from the library. Their insert sizes ranged from 150 to 850 bp with a mean of 320 bp. Fifty pUC clones were randomly selected and analyzed in detail. Southern blot analyses showed that 21 (42%) clones were unique DNA sequences, 20 (40%) clones were repetitive sequences, and 9 (18%) clones had no detectable hybridization. The unique sequences were used further in a secondary screening of a partially digested human genomic DNA library constructed in phage vector, and 4 clones were isolated. The chromosomal locations of these phage clones were confirmed to be in the q23 region of chromosome 11 by fluorescence in situ suppression hybridization. These pUC microclones isolated from the chromosomal region-specific genomic DNA library will be useful in the construction of physical contig maps with yeast artificial chromosome and/or cosmid clones and in the positional cloning of disease-associated genes localized to the q23 region of chromosome 11. PMID- 8486353 TI - Fluorescence in situ hybridization mapping of 25 markers on distal human chromosome 2q surrounding the human Waardenburg syndrome, type I (WS1) locus (PAX3 gene). AB - A total of 25 DNA markers located on the long arm of human chromosome 2 have been mapped by fluorescence in situ hybridization. This region includes the locus for Waardenburg syndrome, type I (WS1), recently found to result, at least in some cases, from mutations of the PAX3 gene. We have established that the chromosomal location of the PAX3 gene is within band 2q36. We also show that three markers in the distal 2q region, including the PAX3 gene, are deleted in a patient with phenotypic features of WS1 associated with a de novo deletion (2)(q35q36.2). The improved physical map of this region should facilitate linkage mapping and positional cloning of loci on distal 2q. PMID- 8486354 TI - Highly informative typing of the human TNF locus using six adjacent polymorphic markers. AB - The human tumor necrosis factor locus (TNF locus) is located within the major histocompatibility complex between the class III genes and HLA-B. We recently characterized and studied two closely linked highly informative dinucleotide repeats (AC/GT)n (designated TNFa) and (TC/GA)k (designated TNFb) in the upstream region of the human TNF-beta (lymphotoxin) gene. We also characterized two linked (TC/GA) and (TC/GA)-like repeats located downstream of the TNF-alpha gene, designated TNFe and TNFd, respectively. Here, we combine these four markers together with a biallelic TC/GA repeat in the first intron of the TNF-beta gene (TNFc) and a biallelic NcoI RFLP (TNFn) to type 105 cell lines from the American Society of Histocompatibility and Immunogenetics Workshop and the Center for Human Polymorphism Studies reference panels of HLA typing cell lines. These 6 polymorphic markers define 35 distinct TNF haplotypes and together with the reference panel can be used for disease association and population genetics studies. PMID- 8486355 TI - Isolation and chromosomal mapping of the human immunoglobulin-associated B29 gene (IGB). AB - The B29 gene encodes a B-cell-specific membrane protein in the immunoglobulin antigen receptor complex. B29 is a crucial member of this receptor complex and is believed to function as an effector of signal transduction in a manner analogous to that of the CD3 components of the T cell antigen receptor. We have isolated a full-length human B29 cDNA clone by using a murine B29 cDNA probe. We show that there is an extremely high degree of evolutionary conservation between the human and mouse proteins, particularly in the transmembrane and intracytoplasmic regions, where the identity is 96%. In addition, the intracytoplasmic region in both proteins contains an identical peptide motif that is present in a number of molecules involved in lymphocyte activation. Genomic Southern blot analysis of human cell lines hybridized with both murine and human B29 cDNAs gives patterns consistent with a single-copy gene occupying a small region of the genomic sequence. Using human B29 cosmid DNA, we have localized the B29 gene to human chromosome 17q23 via fluorescence in situ hybridization. B29 is the first gene localized to this area of the genome. Interestingly, a subset of human B cell chronic lymphocytic leukemias (CLL) has translocations in this locus on chromosome 17. PMID- 8486356 TI - Chromosomal localization of five murine HSP70 gene family members: Hsp70-1, Hsp70 2, Hsp70-3, Hsc70t, and Grp78. AB - The 70,000-D heat shock protein (HSP70) gene family includes both heat-inducible and constitutively expressed genes. We have mapped five murine HSP70 genes to specific sites on three separate chromosomes. Southern blot analysis of Chinese hamster x mouse somatic cell DNAs was used to assign the gene for the 78,000-D glucose-regulated protein (Grp78) to Chromosome (Chr) 2, the male germ cell specific Hsp70-2 and Hsc70t genes to Chr 12 and Chr 17, respectively, and the heat-inducible Hsp70-3 gene also to Chr 17. Southern blot analysis of DNA from the progeny of two multilocus crosses confirmed the Grp78 location on Chr 2 and suggested the order: centromere-Vim-Abl-Grp78-Hc. Similar analysis also confirmed the initial Hsp70-2 assignment to Chr 12 with the order: Hsp70-2-Aat-Igh. The Hsp70-3 and Hsc70t genes on Chr 17, along with the heat-inducible Hsp70-1 gene, were further localized by Southern blot analysis of genomic clones to the H-2 histocompatibility region with the order: Hsp70-1-Hsp70-3-Hsc70t-Bat-6 (human G7a, valyl-tRNA synthetase). PMID- 8486357 TI - Molecular cloning, cDNA sequence, and chromosomal assignment of the human radixin gene and two dispersed pseudogenes. AB - Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. Recent cloning of the murine and porcine radixin cDNAs revealed a protein highly homologous to ezrin and moesin. We have cloned and sequenced the human radixin cDNA and found the predicted amino acid sequence for the human protein to be nearly identical to those predicted for radixin in the two other species. By Southern analyses of Chinese hamster x human somatic cell hybrid DNA and of PCR products derived from hybrids, the coding gene (RDX) was mapped to 11q. Fluorescence chromosomal in situ hybridization with a cDNA plasmid further localized this gene to band 11q23. However, PCR amplification with "radixin specific" primers on the hybrid DNA panel yielded an additional, very similar DNA sequence that was further characterized by direct sequencing of PCR products. This sequence represents a truncated version and the respective locus (RDXP2) was assigned to Xp21.3. Furthermore, by employing a different set of primers, a third sequence was found that was 90% identical to the radixin sequence but contained termination codons and seemed to lack introns. This pseudogene (RDXP1) was mapped to 11p by Southern and PCR analyses. PMID- 8486358 TI - Severe hemophilia A in a female by cryptic translocation: order and orientation of factor VIII within Xq28. AB - We report studies of a female with severe hemophilia A resulting from a complex de novo translocation of chromosomes X and 17 (46,X,t(X;17)). Somatic cell hybrids containing the normal X, the der(X), or the der(17) were analyzed for coagulation factor VIII (F8C) sequences using Southern blots and polymerase chain reaction. The normal X, always late replicating, contains a normal F8C gene, whereas the der(X) has no F8C sequences. The der(17) chromosome containing Xq24 Xq28 carries a functional G6PD locus and a deleted F8C allele that lacks exons 1 15. Also, it lacks the DXYS64-X locus, situated between the F8C locus and the Xq telomere. These results indicate that a cryptic breakpoint within Xq28 deleted the 5' end of F8C, but left the more proximal G6PD locus intact on the der(17) chromosome. As the deleted segment includes the 5' half of F8C as well as the subtelomeric DXYS64 locus, F8C must be oriented on the chromosome with its 5' region closest to the telomere. Therefore, the order of these loci is Xcen-G6PD 3'F8C-5'F8C-DXYS64-Xqtel. The analysis of somatic cell hybrids has elucidated the true nature of the F8C mutation in the proband, revealing a more complex rearrangement (three chromosomes involved) than that expected from cytogenetic analysis, chromosome painting, and Southern blots. A 900-kb segment within Xq28 has been translocated to another autosome. Hemophilia A in this heterozygous female is due to the decapitation of the F8C gene on the der(17) and inactivation of the intact allele on the normal X. PMID- 8486359 TI - Identification and characterization of dinucleotide repeat (CA)n markers for genetic mapping in dog. AB - A large block of simple sequence repeat (SSR) polymorphisms for the dog genome has been isolated and characterized. Screening of primary libraries by conventional hybridization methods as well as by screening of enriched marker selected libraries led to the isolation of a large number of genomic clones that contained (CA)n repeats. The sequences of 101 clones showed that the size and complexity of (CA)n repeats in the dog genome were similar to those reported for these markers in the human genome. Detailed analysis of a representative subset of these markers revealed that most markers were moderately to highly polymorphic, with PIC values exceeding 0.70 for 33% of the markers tested. An association between higher PIC values and markers containing longer (CA)n repeats was observed in these studies, as previously noted for similar markers in the human genome. A list of primer sequences that tag each characterized marker is provided, and a comprehensive system of nomenclature for the dog genome is suggested. PMID- 8486360 TI - Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid. AB - An arrayed library of human heterogeneous nuclear complementary (hnc) DNA was constructed from a somatic cell hybrid (M28) containing an i(12p) marker as the sole human chromosome. Heterogeneous nuclear (hn) RNA of M28 was used to synthesize first-strand hncDNA with a primer (RT) containing a random hexanucleotide at its 3' end. Specific amplification of human sequences from this hncDNA was performed using Alu primers in combination with the RT primer. The products were directionally cloned and an arrayed library was constructed. Experiments indicated that all clones were derived from transcribed sequences. A number of randomly isolated clones were evaluated by Southern and Northern experiments, sequence analysis, and PCR. At least 80% of these clones were of human 12p origin. The number of independent clones in the library was estimated to be approximately 550. Using 60 hncDNA clones as probes, 6 showed positive signals on Northern blots. For 3 of these, the corresponding cDNAs were isolated: clone CD60A1 codes for the cation-dependent mannose 6-phosphate receptor, clone CC6 is a human homologue of the bovine 39-kDa nuclear-encoded NADH:ubiquinone oxidoreductase subunit, and CD18 belongs to the family of tumor necrosis factor receptor proteins. Southern experiments showed the 3 cDNAs to map to human chromosome 12p as expected. Taken together these results show that the generation of a hncDNA library is a useful tool for the isolation of unknown genes located on a human chromosome (fragment) present in a somatic cell hybrid. PMID- 8486361 TI - The genes encoding gonadal and nongonadal forms of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase are closely linked on mouse chromosome 3. AB - The biosynthesis of steroid hormones in the gonads and adrenal glands requires the activities of the enzyme 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD) which catalyzes the NAD(+)-dependent dehydrogenation and subsequent delta 5-->delta 4 isomerization of delta 5-3 beta-hydroxysteroids to delta 4-3 ketosteroids. The mouse expresses four isoforms of 3 beta HSD. 3 beta HSD I is expressed in gonads and adrenal glands and appears to be the major steroidogenic form, 3 beta HSDs II and III are expressed in both liver and kidneys, and 3 beta HSD IV has been detected only in kidneys. To determine the genetic relationship between the 3 beta HSD isoforms, we have mapped the chromosomal locations of the four genes by linkage analysis using gene-specific probes derived from the 3' untranslated regions of 3 beta HSD cDNA clones. The four 3 beta HSD structural genes (Hsd3b) are closely linked within a segment of chromosome 3 that is conserved on human chromosome 1. The order of markers on Chr 3 surrounding Hsd3b is: centromere-Gba-(4.4 +/- 2.2)-Hsd3b-(3.3 +/- 1.9)-Tshb-(6.7 +/- 2.7)-Amy-1. PMID- 8486362 TI - Genetic map of the chicken Z chromosome using random amplified polymorphic DNA (RAPD) markers. AB - Commercially important traits of domestic animals have often been genetically linked to sex chromosomes, such as the Z chromosome of chickens. Using a backcross mapping population between two divergent, inbred lines and random amplified polymorphic DNA (RAPD)-PCR markers, a genetic map of the chicken Z chromosome has been generated. Thirteen Z-linked RAPD markers were identified, mapped, and linked to two RFLPs and one phenotypic marker. The protocol used also generated RAPD markers for the W chromosome. The linkage distances obtained suggest that the RAPD markers are widely distributed throughout the Z chromosome and are likely to be linked to most or all traits of interest on this chromosome. The map provides a preliminary estimate of genetic to physical distance of about 0.5 Mb per centimorgan for the Z chromosome in chickens (male-specific recombination). A similar approach should be applicable to facilitate the mapping and analysis of sex-linked traits in other domestic animals. PMID- 8486363 TI - Identification of the mutation in murine histidinemia (his) and genetic mapping of the murine histidase locus (Hal) on chromosome 10. AB - We cloned a mouse histidase cDNA to identify the mutation in histidinemic mice (his/his) and to determine the relationship of the histidase locus (Hal) both to Chromosome 10 markers and to Hsd, the histidase activity variant locus. The his mutation, a G to A transition at nucleotide +965, changes Arg-322 to Gln (R322Q). Expression of the R322Q allele in COS cells resulted in proportionately reduced amounts of histidase protein and activity compared to the wildtype allele. Hal maps approximately 4 cM distal to the insulin-like growth factor-1 locus and approximately 10 cM proximal to steel. Hsd was found to be tightly linked to Hal, and the low-histidase-activity Hsd allele was associated with reduced histidase mRNA. These studies indicate that the R322Q allele reduces the stability of histidase, position Hal on the Chromosome 10 linkage map, and provide further evidence that Hsd is allelic to Hal. PMID- 8486364 TI - DUMPS cattle carry a point mutation in the uridine monophosphate synthase gene. AB - Deficiency of uridine monophosphate synthase (DUMPS) is a monogenic autosomal recessive disorder in cattle, resulting in early embryonic death of homozygous offspring. To identify the mutation responsible for DUMPS, liver RNA from identified, DUMPS heterozygous animals from the Holstein and Red Holstein breeds was reverse transcribed. Amplification of cDNA with sequence-specific primers and subsequent sequencing of the PCR products revealed a mutation (C-->T) with the loss of an AvaI site at codon 405, resulting in a premature stop codon with a truncated C-terminal catalytic subunit of the protein. A direct DNA test based on PCR was developed and subsequently tested on 102 animals. Complete concurrence of deficiency of UMPS and the presence of the described point mutation in heterozygous animals was observed, thus confirming this point mutation as the basic defect in DUMPS cattle. PMID- 8486365 TI - Application of denaturing gradient gel electrophoresis to detect DNA sequence differences encoding apolipoprotein E isoforms. AB - Apolipoprotein E (apoE) plays an important role in plasma lipid metabolism. Three common isoforms of this protein have been identified by the isoelectric focusing method. In this report we describe a new method for distinguishing these isoforms. Our method employs PCR amplification of the DNA sequence of exon 4 in the apoE gene followed by denaturing gradient gel electrophoresis (DGGE) to distinguish its different melting characteristics. Identification of the ApoE isoforms through DNA melting behavior rather than protein charge differences eliminates the problems associated with isoelectric focusing and facilitates screening for additional mutations at the apoE locus. PMID- 8486366 TI - The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor. AB - The selective amplification by polymerase chain reaction (PCR) of gene fragments corresponding to new G-protein-coupled receptors resulted in the cloning of 18 orphan members of this gene family. Of these, three human clones amplified from genomic DNA (HGMP03, HGMP04, and HGMP05) were shown to be structurally related. Genomic clones corresponding to HGMP03 and HGMP05 were isolated and their putative coding region sequenced. Following the characterization of two interleukin 8 (IL-8) receptors, HGMP03 appeared to encode the high-affinity IL-8 receptor, whereas the partial clone HGMP04 encodes the low-affinity IL-8 receptor. Comparison with the cDNA sequence suggests that the high-affinity receptor gene is split by an intron in the 5' untranslated region. The high affinity receptor gene was mapped by in situ hybridization to the 2q33-q36 region of the human genome. The HGMP05 locus turned out to be a pseudogene for the low affinity IL-8 receptor (87% identity), with multiple frameshifts and point mutations introducing stop codons. Southern blotting on genomic DNA did not allow the further detection of related loci in the human genome. PMID- 8486367 TI - Assignment of the human GTF2F1 gene to chromosome 19p13.3. AB - TFIIF (also termed FC) is a general transcription initiation factor that binds to RNA polymerase II and recruits it to a promoter. TFIIF is a heterodimer composed of 74-kDa (RAP74; gene symbol GTF2F1) and 30-kDa (RAP30; gene symbol GTF2F2) subunits. Here we report the mapping of the human GTF2F1 gene to band 19p13.3. Localization was performed by fluorescence in situ hybridization using the human RAP74 genomic cosmid clone as the probe. PMID- 8486368 TI - Genetic mapping of X-linked ocular albinism: linkage analysis in a large Newfoundland kindred. AB - Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Zmax = 21.96 at theta = 0.01, confidence interval (CI) 0.0005-0.05) and linkage to DXS85 (782; Zmax = 17.60 at theta = 0.07, CI = 0.03-0.13) and DXS237 (GMGX9; Zmax = 15.20 at theta = 0.08, CI = 0.03-0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS 143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10(10):1 over other locations for the disease locus. PMID- 8486369 TI - A human pseudoautosomal gene encodes the ANT3 ADP/ATP translocase and escapes X inactivation. AB - We report that the human ANT3 ADP/ATP translocase gene is a pseudoautosomal gene located proximal to the GM-CSF receptor alpha chain gene (CSF2RA). An ANT3 homologous locus, likely corresponding to a pseudogene, maps to chromosome 9. The ANT3 gene is transcribed from the centromere to the telomere and contains in its first intron a CpG island mapped 1300 kb from the telomere. This gene is transcribed from the Y chromosome and from the active and inactive X chromosomes. This gene thus escapes X-inactivation as predicted for genes belonging to the pseudoautosomal region. PMID- 8486370 TI - Localization of 14 functional J regions in the human T-cell receptor alpha-chain locus. AB - Nearly 60 unique J alpha regions have been identified in human T-cell receptor (TCR) alpha chains to date, yet fewer than one-third of these have been localized within the alpha-chain locus. We report a rapid method for the mapping of productively rearranged J alpha regions using oligonucleotide probes and overlapping phage clones spanning 80 kb of the TCR-alpha locus. Fourteen J alpha regions were mapped using this technique; the positions of five of these have been verified by genomic cloning. PMID- 8486371 TI - Localization of the gene-encoding upstream stimulatory factor (USF) to human chromosome 1q22-q23. AB - The upstream stimulatory factor, USF, is a ubiquitously expressed cellular transcription factor that binds to a symmetrical DNA sequence that is found in a variety of viral and cellular promoters. A full-length cDNA encoding the 43-kDa USF protein has previously been isolated. USF contains both helix-loop-helix and leucine repeats, which are involved in regulating its DNA binding and dimerization properties. We report the use of mouse-human somatic cell hybrids and in situ hybridization in localizing the gene-encoding USF to human chromosome 1q22-q23. PMID- 8486372 TI - Characterization of a DNA sequence family in the Prader-Willi/Angelman syndrome chromosome region in 15q11-q13. AB - IR4-3R (D15S11) is an anonymous DNA sequence from human chromosome 15. Using YAC cloning and restriction enzyme analysis, we have found that IR4-3R detects five related DNA sequences, which are spread over 700 kb within the Prader Willi/Angelman syndrome chromosome region in 15q11-q13. The RsaI and StyI polymorphisms, which were described previously, are associated with the most proximal copy of IR4-3R and are in strong linkage disequilibrium. IR4-3R represents the third DNA sequence family that has been identified in 15q11-q13. PMID- 8486373 TI - Refinement of the localization of the X-linked ocular albinism gene. AB - Although physical and genetic mapping studies assigned the X-linked ocular albinism gene to Xp22.3, the exact gene order in this region is still unclear. We present additional genetic mapping data concerning X-linked ocular albinism that suggests the consensus order Xpter-STS-DXS237-KAL-(OA1, DXS143)-DXS85-DXS16-Xcen. PMID- 8486374 TI - S-laminin: mapping to mouse chromosome 9 and expression in the linked mutants tippy and ducky. AB - S-Laminin, a homologue of the laminin B1 chain, is present in a subset of basal laminae, including those of the skeletal neuromuscular junction and the renal glomerulus. Here, we show that the distribution and apparent size of murine S laminin are similar to those documented previously for rat and human. We then use interspecific backcross analysis to map the S-laminin (Lams) gene to mouse chromosome 9. Thus, it is unlinked to genes for the laminin A, B1, and B2 chains. Finally, because the Lams gene mapped near two mutations that affect neuromuscular function, ducky (du) and tippy (tip), we assayed S-laminin by Southern blotting, immunoblotting, and immunohistochemistry in these mutants. No abnormality of the S-laminin gene or protein was detectable in either mutant. PMID- 8486375 TI - A mutation in the amino-terminal end of the triple helix of type II collagen causing severe osteochondrodysplasia. AB - Type II collagen is coded by a large gene (COL2A1) consisting of 54 exons on chromosome 12. During the past few years several cartilage disorders have been linked to this gene, and some specific nucleotide changes have been identified in patients. In a spondyloepiphyseal form of chondrodysplasia, the three mutations found so far are all in exon 48 in the region coding for the carboxyl-terminal end of the triple helix. Since folding of the type II collagen polypeptides to the triple helix is initiated from the carboxyl-terminal end, it has been suggested that mutations in this region typically result in severe cartilage diseases. Here we report a novel mutation located in the area coding for the amino-terminal part of the triple helix in a sporadic patient with spondyloepiphyseal dysplasia (SED). The mutation, a substitution of G1063 to A, which results in the conversion of Gly154 to Arg, was identified using exon specific amplification of genomic DNA and subsequent analyses with denaturing gradient gel electrophoresis and single-strand conformation polymorphism. The substitution was not found in any other SED patient in Finland. This novel mutation demonstrates that amino acid substitutions in the amino-terminal part of the type II collagen triple helix can also result in SED. PMID- 8486376 TI - Artificially generated data sets for testing DNA sequence assembly algorithms. AB - We have developed a set of tools, genfrag, to fragment and optionally mutate a DNA sequence to generate benchmark data sets for testing DNA sequence assembly algorithms. Data parameters can be systematically and independently varied to explore the range of data--and corresponding performance of assembly tools- encountered on large-scale random, or "shot-gun," sequencing projects. PMID- 8486377 TI - The order and orientation of a cluster of metalloproteinase genes, stromelysin 2, collagenase, and stromelysin, together with D11S385, on chromosome 11q22-q23. AB - A cluster of metalloproteinase genes, stromelysin, fibroblast collagenase, and stromelysin 2 together with the anonymous DNA marker D11S385, was mapped using pulsed-field gel electrophoresis to a 135-kb region of chromosome 11q22-q23. The physical proximity of these markers was subsequently confirmed using two YAC clones, and their relative order was established as stromelysin 2-collagenase stromelysin-D11S385. The pattern of marker representation in a panel of radiation reduced chromosome 11 hybrids suggests that the metalloproteinase gene/D11S385 cluster is orientated with STMY2 closest to the centromere. PMID- 8486378 TI - Genes for the dimerization cofactor of hepatocyte nuclear factor-1 alpha (DCOH) are on human and murine chromosomes 10. AB - Hepatocyte nuclear factor-1 alpha (HNF-1 alpha; gene symbol, TCF1) forms dimers with itself as well as with HNF-1 beta and regulates the expression of several liver-specific genes. Recently, a dimerization cofactor of hepatocyte nuclear factor-1 alpha, called DCOH, has been identified. Here, we report the chromosomal localization of the genes for this cofactor to chromosomes 10 in both humans and mice by Southern blot analyses of somatic cell hybrids. PMID- 8486379 TI - A recurrent deletion in the antithrombin gene, AT106-108(-6 bp), identified by DNA heteroduplex detection. PMID- 8486380 TI - The loss of a polymorphic glycosylation site caused by Thr-927-->Ile is linked to a second polymorphic Val-816-->Ile substitution in lysosomal alpha-glucosidase of American blacks. PMID- 8486381 TI - Human myosin-binding protein H (MyBP-H): complete primary sequence, genomic organization, and chromosomal localization. AB - Vertebrate striated muscle contains a set of myosin-associated proteins with discrete distributions in the A-band. Some of these proteins, including MyBP-H and MyBP-C, are characterized by a series of internal repeats (motifs) with homology to either the C2-set of the immunoglobulin superfamily or the fibronectin type III repeat. These repeats are predicted to be involved in protein-protein interactions within the myofibril. The cDNA sequence, the genomic organization, and the chromosomal localization of the human homologue of MyBP-H are presented. The 1.8-kb cDNA encodes a 52-kDa polypeptide containing two Ig-C2 and two type III repeats. The mRNA is expressed in a skeletal muscle-specific pattern. A 28-kb region of genomic sequence has been isolated that encompasses the 5' and 3' ends of the cDNA. This region includes 4.2 kb of upstream sequence with a potential promoter and 14 kb of downstream sequence containing the polyadenylation site. The chromosomal assignment was made by high resolution chromosomal in situ hybridization. This method maps the gene to chromosome 1q32.1. The repeat structure described previously in chicken MyBP-H and MyBP-C was also detected in human MyBP-H. The primary sequence of the C-terminal Ig-C2 motif and its predicted secondary structure have been extensively conserved in MyBP-H homologues and other members of the MyBP family. This Ig-C2 motif has been implicated in myosin binding. PMID- 8486382 TI - A simple and powerful method for linkage analysis by amplification of DNA from single sperm cells. AB - Haplotypes of three bovine casein loci were analyzed as a way of determining genetic linkage. A total of 330 individual sperm cells from a triply heterozygous bull were selected by means of a new method involving fixing the sperm cells into low-melting-point agarose gels. The method is simple and very accurate with an efficiency close to 100% for picking sperm cells and producing amplifiable DNA templates, circumventing the complicated statistical analysis mandated by automated cell sorting. The DNA was amplified in a two-step polymerase chain reaction (PCR) to achieve the necessary high specificity of amplification. In the first reaction, primers flanking the polymorphic site at each locus were used. The PCR product from the first reaction was then reamplified in a second PCR using primers that create allele-specific restriction sites (ACRS) in the PCR products for two of the three loci, allowing the alleles to be determined by gel electrophoresis. No recombinants were found among the 330 single sperm cells analyzed, giving a lod score higher than 30 and proving a very strong linkage between bovine casein genes. PMID- 8486383 TI - New mouse primary retinal degeneration (rd-3). AB - A new mouse retinal degeneration that appears to be an excellent candidate for modeling human retinitis pigmentosa is reported. In this degeneration, called rd 3, differentiation proceeds postnatally through 2 weeks, and photoreceptor degeneration starts by 3 weeks. The rod photoreceptor loss is essentially complete by 5 weeks, whereas remnant cone cells are seen through 7 weeks. This is the only mouse homozygous retinal degeneration reported to date in which photoreceptors are initially normal. Crosses with known mouse retinal degenerations rd, Rds, nr, and pcd are negative for retinal degeneration in offspring, and linkage analysis places rd-3 on mouse chromosome 1 at 10 +/- 2.5 cM distal to Akp-1. Homology mapping suggests that the homologous human locus should be on chromosome 1q. PMID- 8486384 TI - Cystatin C (CST3), the candidate gene for hereditary cystatin C amyloid angiopathy (HCCAA), and other members of the cystatin gene family are clustered on chromosome 20p11.2. AB - The cystatin C gene (CST3) encodes a low-molecular-weight cysteine proteinase inhibitor belonging to family II of the cystatin superfamily and is mutated in cases of hereditary cystatin C amyloid angiopathy (HCCAA). CST3, which along with other family II cystatin genes is a member of the cystatin gene family, has been assigned to chromosome 20. To investigate the genomic organization on chromosome 20, the CST3 gene and related sequences were regionally mapped by fluorescence in situ hybridization (FISH), Southern blot, and pulsed-field gel electrophoresis (PFGE) analysis using the cDNA cystatin C probe C6a and three genomic probes, C3E1, C3E2, and C3E2-2. Probe C3E2-2, which like probe C3E2 is specific for CST3, hybridized to only one HindIII and one XbaI fragment on Southern blots and to a 300-kb BssHII PFGE fragment. FISH with probe C3E2 mapped this locus to chromosome 20p11.2, with an FL-pter value of 0.37 +/- 0.07 on the physical map. Probe C3E1 containing the most conserved cystatin gene exon (exon 1) and its flanking sequences hybridized with more fragments, e.g., to eight XbaI and nine HindIII fragments on conventional Southern blots and to eight SmaI, two BssHII (900 and 300 kb), and two NotI fragments after PFGE. FISH with C3E1 revealed only one single site at 20p11.2 with an FL-pter value of 0.37 +/- 0.04, identical to that obtained with C3E2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486385 TI - Polymorphic SSR (simple-sequence-repeat) markers for chromosome 20. AB - Chromosome 20-specific simple-sequence-repeat (SSR) markers were developed from a flow-sorted phage library (LL20NS01), subcloned in Bluescript, and screened with a tetranucleotide repeat, (AAAG)6, to identify potentially polymorphic loci. Of 100 clones sequenced, 39 were selected to construct primers. Of these 39, 22 were polymorphic. Reference to the CEPH linkage database (version 5) permitted genetic mapping of 16 of the new markers to specific regions of chromosome 20. Ten of the SSRs showed heterozygosity indices (above 70%) that would qualify them as potential index markers. PMID- 8486386 TI - Subclustering of human immunoglobulin kappa light chain variable region genes. AB - The human immunoglobulin kappa light chain (IgK) locus includes multiple variable region gene segments (Vk) that can be divided into four subgroups. Oligonucleotide primers were designed to amplify specifically gene segments of the VkI, VkII, and VkIII subgroups using the polymerase chain reaction (PCR). Product sequences were subcloned, sequenced, and compared. Phylogenetic analyses of sequences within each subgroup indicate that some subgroups can be subdivided further into "sub-subgroups." The history of Vk segment duplications apparently includes at least two separate periods, the first giving rise to the subgroups and the second generating further complexity within each subgroup. Duplications of large pieces of DNA (demonstrated by others through pulsed-field gel electrophoresis) also played a role. Rates of synonymous and non-synonymous base changes between pairs of sequences suggest that natural selection has played a major role in the evolution of the Vk variable gene segments, leading to sequence conservation in some regions and to increased diversity in others. PMID- 8486387 TI - Characterization of the mouse thrombospondin 2 gene. AB - We have characterized the exon/intron organization, complete 3' untranslated region (3'-UTR), and approximately 2.5 kb of the promoter/5' flanking region of the mouse thrombospondin 2 (TSP2) gene. The sizes of exons and the pattern of interruption of the reading frame by introns are highly conserved in mouse TSP2 in comparison with mouse or human TSP1, a finding that suggests a close evolutionary relationship between the two genes. The TSP2 and TSP1 genes are also similar in that the 3'-UTRs of both genes contain multiple TATT and ATTT(A) motifs that might function as mediators of mRNA stability. However, the sequences of the promoter regions in TSP1 and TSP2 are very different; in particular, the TSP2 gene lacks the serum response element and the NF-Y binding site that have been implicated in the serum response of the human TSP1 gene. The structure of the TSP2 gene is consistent with emerging evidence supporting the view that TSP1 and TSP2 perform overlapping but distinct functions. PMID- 8486388 TI - Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q. AB - We have used the polymerase chain reaction to map the gene encoding human flavin containing monooxygenase (FMO) form II (N. Lomri, Q. Gu, and J. R. Cashman, 1992, Proc. Natl. Acad. Sci. USA 89: 1685-1689) to chromosome 1. We propose the designation FMO3 for this gene as it is the third FMO gene to be mapped. The two other human FMO genes identified to date, FMO1 and FMO2, are also located on chromosome 1 (C. Dolphin, E. A. Shephard, S. Povey, C. N. A. Palmer, D. M. Ziegler, R. Ayesh, R. L. Smith, and I. R. Phillips, 1991, J. Biol. Chem. 266: 12379-12385; C. Dolphin, E. A. Shephard, S. F. Povey, R. L. Smith, and I. R. Phillips, 1992, Biochem. J. 286: 261-267). The localization of FMO1, FMO2, and FMO3 has been refined to the long arm of chromosome 1. Analysis of human metaphase chromosomes by in situ hybridization confirmed the mapping of FMO1 and localized this gene more precisely to 1q23-q25. PMID- 8486389 TI - Isolation and FISH mapping of 80 cosmid clones on the short arm of human chromosome 3. AB - We have isolated and mapped by fluorescence in situ hybridization 80 new cosmids on the short arm of chromosome 3. These markers were isolated from a radiation reduced hybrid, DM1, made from a cell line that was monochromosomal for human chromosome 3. Selected cosmids were used in double-label cohybridization experiments in which polymerase chain reaction products, generated by an Alu oligonucleotide primer from genomic DNA, were used for chromosome banding. Fifty six of the cosmid probes map between 3p14.3 and 3p22 while 24 other probes cluster around bands 3p23-3p25. Three probes that appeared to map close to the chromosome 3 region bearing a t(3,8)p14.2; q24.1 translocation associated with renal cell carcinoma were analyzed by interphase mapping techniques and hybridized to metaphase spreads from the translocation cell line. These 80 probes will be useful in the elucidation of genetic alterations associated with diseases such as small cell lung carcinoma, renal cell carcinoma, and von Hippel-Lindau disease. PMID- 8486391 TI - Factors controlling the reactivity of immature and mature T cells to Mls antigens in vivo. PMID- 8486390 TI - Accurate characterization of porcine bivariate flow karyotype by PCR and fluorescence in situ hybridization. AB - The 19 chromosomal pairs of the swine karyotype are resolved into 18 peaks denoted A to Q and Y by dual-beam flow cytometry. The chromosomal content of six peaks has previously been determined by analyzing male/female differences, karyotypes of animals carrying translocations, and PCR studies of genes with known assignments. For the remaining chromosomes, putative assignments to flow peaks were deduced from comparison of DNA contents, determined by flow cytometry, and chromosomal size. We present here the complete characterization of the pig bivariate flow karyotype using the PARM-PCR technique combined with fluorescence in situ hybridization. Chromosome-specific probes were generated by PCR amplification of 300 sorted chromosomes with primers under nonspecific conditions and used to paint chromosomes by FISH. The chromosomal content of each peak was identified: peaks A (chromosome 1), B (13), C (6), D (2), E (14), F (3), G (7), H (9,4,X), H1 (9), I (15), J (8), K (5), L (10), M (12), N (16), O (11), P (17), Q (18), Y (Y). We were able to characterize perfectly the pig bivariate flow karyotype. Such techniques could be applied to any other species. PMID- 8486392 TI - Are there cellular superantigens? PMID- 8486393 TI - Immunoregulatory effects of superantigens: interactions of staphylococcal enterotoxins with host MHC and non-MHC products. AB - Staphylococcus aureus carries a highly conserved set of genes which encode a set of secreted enterotoxins. Although it is likely that these enterotoxins affect the host/parasite in favor of the bacterium, we do not understand the molecular basis of this interaction. We summarize recent evidence that defines two types of interaction between the bacterial toxin and host cellular receptors that may subvert the host immune response to S. aureus. An interaction between the toxin and class II products on APC can result in inhibition of costimulatory activity and thus impair clonal expansion of T cells specific for bacterial antigens. Studies using anti-class II antibodies suggest that this may reflect transmission of a negative signal to APC after ligation of class II products. A second interaction between a subset of toxins, including SEC, with non-MHC products stimulates both T-cell proliferation as well as toxin-specific cytotoxic T cells (CTL). We put forward the hypothesis that this interaction reflects binding of a VCAM-1-like subsequence of SEC to VLA-4 expressed by activated target cells. We suggest that this interaction may serve to inhibit the host response by subversion of lymphocyte homing to sites of infection by SEC-producing staphylococci and by local elimination of (VLA-4+) memory T cells. PMID- 8486394 TI - T-cell receptor beta-chain binding to enterotoxin superantigens. AB - The last few years have seen an enormous jump in our knowledge and understanding of T-cell activation by superantigens. Clearly, a great number of infectious and parasitic organisms utilize superantigens as part of a strategy to evade the immune response of their host. The ability to modulate superantigen effects will give us new means to fight infections, and the knowledge of T-cell activation that we have gained from study of superantigens will, in turn, allow us to modulate the immune system in new ways. PMID- 8486395 TI - Technetium-99 m labelling of DD-3B6/22 antifibrin monoclonal antibody fragment Fab' for thrombus imaging. AB - The antifibrin DD-3B6/22 monoclonal antibody Fab' fragment, a murine immunoglobulin, IgG3, has been labelled with technetium-99 m (99mTc) via a transchelation reaction, to specific activity in excess of 30 mCi/mg protein. The radiolabelling of Fab' was dependent on time, temperature, pH, antibody concentrations and nature of intermediary transchelation complex used. The resultant radioconjugate was stable in vitro and in vivo. Blood clearance of 99mTc-Fab' in rat followed two compartment kinetics with the half time of the fast phase being 0.5 h. The main route of excretion was via the kidneys with little uptake indicated by other tissues. The results suggest that the inherent specificity of the antibody, small molecular size, rapid plasma clearance, high specific radioactivity, together with the physical properties of the 99mTc label, combine to make this labelled monoclonal antibody (MoAb), potentially suitable as a radiopharmaceutical for the scintigraphic detection of thrombi in humans. PMID- 8486396 TI - A re-examination of the molecular basis of cell movement. AB - A model for cell movement is presented. It is suggested that cells do not migrate on collagen using their VLA (very late antigen) integrins that bind this extracellular matrix protein. Rather, the cells utilize alpha v integrins to bind endogenously produced fibronectin, which binds to the underlying collagen. It is envisaged that cells proceed by a process of engagement and disengagement of alpha v integrins to the extracellular matrix, somewhat analogous to the motion of a monkey climbing a tree. Secretion of isoforms of the adhesion modulator, thrombospondin, regulates disengagement of the integrin from its ligand in migrating cells. The integrin disengagement signal is mediated by thrombospondin cross-linking the alpha v integrin to an integrin accessory molecule and thus activating protein kinases. The cross-linked receptor complex undergoes recycling back along actin stress fibres, guided by the integrin beta-subunit. After endocytosis and protein sorting the alpha v integrin is transported back to the leading edge off migrating cells in vesicles guided by the tubulin-binding capabilities of an integrin accessory molecule. Direct attachment to collagen required for processes, such as matrix contraction, is mediated by VLA integrins which displace alpha v integrins from points of attachment during integrin recycling, possibly through an alpha v beta 1 intermediary receptor. PMID- 8486397 TI - Selective modification and immune evasion: a hypothesis. AB - A hypothesis is proposed asking why enzyme neutralization is not an effective host-response to a parasite despite the fact that some parasite housekeeping enzymes are highly immunogenic. It is hypothesized that although the structural domain can be immunogenic, the active sites of the parasite enzyme molecules have converged evolutionarily to resemble the functional part (active sites) of host's enzyme molecules, by structural modification/rearrangement (amino acid substitution/polypeptide chain folding) with the effect: (i) of functional adaptation to the host environment; and (ii) to escape detection of active sites by the host as non-self, allowing the parasite to be exposed to antiparasite enzyme antibodies, without deleterious effects on the parasite. PMID- 8486398 TI - Alteration within a discrete region of the H-2Ld alpha 1 helix upon association with human beta 2 microglobulin. AB - The utilization of the beta 2-microglobulin (B2m) exchange assay allowed for the association of H-2Ld with human B2m. Upon association with H-2Ld, human B2m induces structural alterations in H-2Ld that appear dependent upon xenogeneic B2m amino acid sequence variability. In this regard, xenogeneic B2m exchange is used as a tool to induce structural alterations in class I as a means of analysing the structural-functional relationship of B2m/class I association. Incorporating H 2Ld site-directed mutants into the experimental approach provided strong evidence that B2m makes indirect contact with discrete class I specific amino acid positions located in the helical region of the alpha 1 domain. PMID- 8486399 TI - Electroporation and DNA-dependent cell death in murine macrophages. AB - The difficulty of transfecting primary macrophages and macrophage cell lines has meant that relatively few studies on regulation of gene expression have been performed in these cells. This study has optimized an electroporation procedure for the macrophage cell line RAW 264, but shows that introduction of DNA into the cytoplasm of primary macrophages by electroporation is toxic to the cells. It is proposed that this cell death may have a physiological role in defence against certain viral infections which result in accumulation of cytoplasmic DNA. RAW 264 cells were efficiently transfected by electroporation, but electroporated bone marrow derived macrophages (BMM) showed large scale cell death over a period of 12 h. Electroporation without DNA was not toxic and DNase treatment of samples before transfection prevented cell death. The toxicity of DNA was concentration dependent and sequence-independent. Synthetic, genomic and plasmid DNA all caused cell death. This sensitivity to DNA seems to be distinct from the antiviral state induced by double-stranded RNA and may be part of an uncharacterized viral defence system. PMID- 8486400 TI - Human natural killer (NK) cells: requirements for cell proliferation and expansion of phenotypically novel subpopulations. AB - Previous studies established that the high density (resting) natural killer (NK) cell subset (R-NK) of peripheral blood NK cells is unresponsive to interleukin-2 (IL-2) but can be induced to proliferate when cultured with gamma-irradiated malignant melanoma (MM-170) cells or mitomycin-C-treated activated T cells in the presence of an IL-2-conditioned medium (IL-2-CM). This study has examined additional requirements of this activation process. The induction of proliferation was dependent on cell to cell contact with metabolically active stimulator cells, although no evidence was obtained that stimulation was effected by soluble factors produced by the stimulator cells. Compared with IL-2-CM, rIL-2 was an inefficient costimulator for the induction of NK cell proliferation, suggesting that factors in IL-2-CM were required in addition to IL-2, but rIL-2 was as efficient as IL-2-CM in maintaining the proliferation of activated NK cells. Under optimum culture conditions, NK growth of up to 3200-fold occurred during a proliferation cycle of 18 days. Phenotypic analysis of the culture generated quiescent NK cells revealed novel heterogeneity in CD16 (Fc gamma RIII) and CD56 (N-CAM) expression. Some NK cells lacked expression of both CD16 and CD56 (as identified using currently available monoclonal antibodies), while other NK cells showed differential CD16 epitope expression. Since quiescent NK cells can be obtained in large numbers and high purity, they will be a convenient source of NK cells to study the molecular processes involved in initiating NK cell proliferation. PMID- 8486401 TI - Reduced secretion of IL-1 beta by peritoneal cells from patients on continuous ambulatory peritoneal dialysis. AB - The endogenous and lipopolysaccharide stimulated interleukin (IL)-1 beta production in vitro by peritoneal monocytes/macrophages from patients on continuous ambulatory peritoneal dialysis (CAPD) was examined during episodes of infection and inflammation. Measurement of immunoreactive IL-1 beta and bioactive IL-1 in both supernatants and cell lysates after culture for 18 h revealed that these cells secreted a significantly lower proportion of total IL-1 than that measured for elutriated blood monocytes. For the inflammatory peritoneal cells, the proportion of total IL-1 beta that was cell-associated resembled that reported for more differentiated pulmonary alveolar macrophages and for adherent monocytes cultured for 18 h prior to stimulation. A similar reduced ability to secrete IL-1 beta was detected for unfractionated peritoneal cells from CAPD patients without peritonitis upon direct comparison with the IL-1 beta production by blood mononuclear cells from the same patients. These results suggested that at a time when a pro-inflammatory response by extravasated host monocytes/macrophages was required by CAPD patients with peritonitis, only a minor proportion of total IL-1 beta would be available extracellularly. This study highlights the rapidity with which extravasated monocytes lose their ability to secrete IL-1 beta and raises the possibility that an important site of utilization of IL-1 beta in vivo may be intracellular in its location. PMID- 8486402 TI - Reduction of the cost of testing for antibody to human immunodeficiency virus, without losing sensitivity, by pooling sera. AB - The sensitivity of testing pooled sera instead of individual sera for antibody against human immunodeficiency virus (HIV) was evaluated using a non-competitive enzyme-linked immunosorbent assay (ELISA). For this purpose, 42 HIV antibody positive sera were titrated and introduced into 42 sets of pools of 2, 4, 8, 16, 32 or 64 sera in such a manner that each pool had one positive sample and the rest, HIV antibody negative sera. When the pools were tested in ELISA, all pools with high titred antibody positive sera were reactive irrespective of pool size, while some of the pools containing medium or low titred sera were non-reactive when pool size exceeded 16. Subsequently the pool size was limited to 16. When 208 previously unscreened samples were tested in 52 pools of 4, 26 pools of 8 or 13 pools of 16 sera, or individually, 6 antibody positive sera were correctly identified. Thus, it was found that the pooling method did not reduce the sensitivity of ELISA test, whereas the cost was reduced to less than half of that of individual testing. PMID- 8486403 TI - T lymphocytes in pulmonary tuberculosis. AB - T cells and their sub-populations were evaluated with respect to reactive, intermediate and unreactive forms of tuberculosis as classified by Lenzini. Significant CD4 lymphopenia and a reduction of CD4/CD8 ratios were found in patients with reactive tuberculosis. It was observed that there was a B lymphocytosis, CD8 lymphocytosis and a reduction of CD4/CD8 ratio in patients with intermediate and unreactive forms of tuberculosis. The T lymphocytes and CD4 subset were unchanged. There was no significant difference in the lymphocytes and sub-populations among the intermediate and unreactive groups. PMID- 8486404 TI - Antigenic similarity of a cultivable acid fast bacterium to Mycobacterium leprae. AB - A cultivable acid fast stainable bacterium obtained from leprosy nodule showed similarity to M. leprae in antigenicity to serum antibodies of lepromatous leprosy patients. The antigenic similarity has been seen more clearly in the delipidified cell components of both these bacteria. An antigen of 35-38 kDa has been seen as a common antigen between M. leprae and the cultivable bacilli with binding ability to sera from leprosy patients. This cultivable bacterial component could be used for serodiagnosis of lepromatous leprosy. PMID- 8486405 TI - Immunodiagnosis of group-A streptococci by latex agglutination assays with monoclonal or monospecific polyvalent antibodies. AB - Seven clones of murine monoclonal antibodies specific for group-A streptococci were generated. All of them were of IgM isotypes and recognized trypsinized as well as nontrypsinized group-A streptococci and polysaccharide. These were devoid of reactivity with streptococci-B, -C, -G and Staphylococcus aureus. Polyclonal antibodies against group-A polysaccharide (APS) were also raised in rabbits by linking APS to bovine serum albumin, and rendered monospecific by adsorption. Latex agglutination assays were developed employing both types of antibodies. The assay employing monospecific polyvalent antibodies had a sensitivity of 12.5 ng APS/ml as compared to 1 microgram APS/ml for latex sensitized with monoclonal antibodies. Both assays were specific, as no agglutination was observed with polysaccharides obtained from streptococci-B, -C, -G, Staph. aureus, Cornybacterium diptheriae, Candida albicans, Candida spp., Morexella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Streptococcus agalactiae, Strep. pneumoniae. Salmonella typhi and S. paratyphi A and B. Throat swabs from children obtained in duplicate, when tested for the presence of streptococci-A, showed a good correlation of the results obtained by latex agglutination assay with the microbial culture test and serogrouping. PMID- 8486406 TI - Evaluation of direct gas-liquid chromatography of CSF in rapid diagnosis of acute bacterial meningitis. AB - A comparison of culture and lactic acid level from 50 patients suffering from bacterial meningitis and 25 controls was done to evaluate the role of direct GLC analysis of CSF for early diagnosis of bacterial meningitis. The study revealed that the CSF lactic acid level was higher in 48 out of 50 cases. Only in 30 patients the causative agent of the disease could be established by conventional techniques. Quantitative estimation of lactic acid was found to be useful. PMID- 8486407 TI - Coagglutination for rapid testing of toxin producing Corynebacterium diphtheriae. AB - Coagglutination test was standardised for rapid detection of diphtheria toxin after primary culture of C. diphtheriae isolates on conventional Loeffler's medium. The procedure was optimised with diphtheria toxoid (DT)-antidiphtheritic serum (ADS) system wherein Cowan-I strain of Staphylococcus aureus was sensitised with ADS. Toxoid in the range of 1.02 lf/ml to 4200 lf/ml could be detected by the present procedure. Toxin of C. diphtheriae could be demonstrated in five of eight clinical isolates, this correlated with the conventional guinea pig pathogenicity test. The coagglutination test thus needs further confirmation of its potential as a simple and satisfactory test for rapid detection of toxin producing C. diphtheriae. PMID- 8486408 TI - Insecticide susceptibility status & enzyme profile of Aedes albopictus populations from different localities of Maharashtra state. AB - Susceptibility status of five populations of Ae. albopictus mosquitoes from Maharashtra state, to DDT, malathion, fenitrothion, bromophos, propoxur and deltamethrin was studied and compared with the laboratory population. Four populations survived when adults were exposed to 4 per cent DDT impregnated paper for 2 h; though three of these populations had lower DDT-LC50 values at larval stages in comparison with the laboratory population. Results of topical application of DDT on these four populations supported these findings by showing comparatively higher LD50 values at adult stages in comparison with the laboratory population. All the populations were highly susceptible to other pesticides tested i.e., malathion, fenitrothion, bromophos, propoxur and deltamethrin. These populations were distinguished from each other by esterase isoenzyme patterns. PMID- 8486409 TI - Hepatitis E virus infection in pregnant rhesus monkeys. AB - Ten non-pregnant female monkeys and four pregnant monkeys (all Macaca mulatta) in the last third of their gestation period were infected intravenously with the stool sample of a patient with hepatitis E virus infection (immuno electronmicroscopy positive for hepatitis E virus). Four more non-pregnant monkeys were inoculated with a lower dose (less number of virus particles by IEM) of a stool sample collected on a different day from the same patient. The average incubation period as evidenced by the rise of serum alanine transferase in the non-pregnant monkeys, was 36.4 +/- 4.9 days. The dose of the virus did not affect the incubation period. Two of the pregnant monkeys had incubation periods of 9 and 13 days respectively. They delivered healthy babies on 40th and 53rd day respectively after inoculation. At the age of 11 months, both babies were negative for anti-HEV antibodies. One monkey which delivered a healthy baby on the 2nd day after inoculation had incubation period of 36 days. The baby of this monkey was anti-HEV positive at the age of 11 months. The incubation period was 41 days in the fourth monkey which delivered a macerated foetus on the 36th day after infection. No fatality was recorded in the infected monkeys. Bile samples collected from all monkeys showed strong signals in nested polymerase chain reaction (PCR). It seems that the incubation period in pregnant monkeys was determined by the state of pregnancy. PMID- 8486410 TI - Observations on the breeding habitats of Aedes aegypti in Calcutta following an episode of dengue haemorrhagic fever. AB - A year-long (Nov. 1990-Oct. 1991) search for Ae. aegypti larvae was made of all water containers in and around fixed 100 houses at Bowbazar area in Calcutta following an episode of DHF. Out of 10151 containers searched, 615 (6%) were positive. Masonry tanks were the major (64.2%) and preferred (17%) breeding sites of Ae. aegypti. Indoor containers (6.7%) were more conducive to breeding of the vector species than the outdoor ones (3%). Breteau index showing wide variation (25 in December '90 to '93 in August 1991) proved to be the best for measurement of density of larval population of Ae. aegypti and paralleled the fluctuation in both rainfall and humidity. Role of temperature was not pronounced. It was noted that cases of DHF occurred even with the lowest Breteau index in December. PMID- 8486411 TI - Hemolysis reduction in plasmapheresis by module design: operating with pulsed flow filtration enhancement. AB - This study is an investigation into the effects of module design on hemolysis levels during the filtration enhancement of plasmapheresis using pulsed blood flow. Two polypropylene hollow fiber modules (F1 and F2) were compared under steady and pulsed flow conditions. The fiber lengths and membrane areas of the respective filters were 136 mm, 0.1 m2 and 226 mm, 0.25 m2 and were used at wall shear rates of 400 and 600 s-1. Fresh citrated bovine blood was circulated at 90 ml/min through their fibers with permate and retentate being recirculated. Plasma samples were analysed by the Cripps method to obtain the mean free hemoglobin concentration. A comparison of the average hemoglobin released with time per fiber, and per unit length allowed an assessment of the effects of fiber length and shear rate on hemolysis levels. It was concluded that a reduction in area and fiber length would reduce hemolysis levels and design equations are suggested to find the optimum length. PMID- 8486412 TI - A process for enhancing selectivity and limiting plugging in plasmafractionation for APOB removal. AB - A new process using pressure and flow pulsations was investigated in the second stage of cascade filtration for ApoB removal. Due to enhanced filtration by the pulsations, the retentate flow vanished naturally without clamping the line, which reduced albumin and ApoA1 losses. The performance of Eval 4A and cellulose PF100 filters in this case were compared with that of classical dead end mode at a plasma flux of 18 ml/(min m2). The apparent sieving coefficient for small proteins (albumin, ApoA1) under pulsed conditions increased with increasing pressure instead of dropping as in dead end mode. In both cases the ApoB sieving coefficients remained below 0.02. These encouraging results were accompanied by a slower rise of transmembrane pressure showing a decrease of membrane plugging. Thus, the recovery of albumin and ApoA1 is increased while ApoB removal remains constant, which improves the selectivity of the fractionation stage. PMID- 8486413 TI - Effect of recombinant erythropoietin on electrolytes and nutrition in end-stage renal disease patients. PMID- 8486414 TI - A technique for the laboratory determination of recirculation in single needle dialysis. AB - Recirculation is an important factor in single needle dialysis and, if high, can compromise treatment efficiency. To provide information regarding recirculation characteristics of access devices used in single needle dialysis, we have developed a new technique to characterise recirculation and have used this to measure the recirculation of a Terumo 15G fistula needle and a VasCath SC2300 single lumen catheter. The experimentally obtained results agreed well with those established clinically (8.5 +/- 2.4% and 18.4 +/- 3.4%). The experimental results have also demonstrated a dependence on access type, pump speeds and fistula flow rate. A comparison of experimental data with theoretical predictions showed that the latter exceeded those measured with the largest contribution being due to the experimental fistula. PMID- 8486415 TI - The epidermo-peritoneal potential in patients treated with continuous ambulatory peritoneal dialysis. AB - At physiologic pH, S. epidermidis moves along an electrical potential gradient. We measured the epidermo-peritoneal electrical potential (EPP) in 23 end-stage renal failure patients treated with CAPD. There was a negative correlation between the mean EPP and the patient's age (r = 0.47, p = 0.016), but no correlation between the mean EPP and the duration of treatment (r = 0.003, p = 0.5). The EPP was greater in those patients with a history of recurrent bacterial peritonitis due to S. epidermidis [median EPP 23 mv (95% confidence limits 16 51)] compared to those with only one or no episodes of bacterial peritonitis due to S. epidermidis infection [11 mv (9-17), p < 0.05]. Thus electrical gradients caused by the presence of the CAPD catheter could contribute to colonisation and subsequent infection by skin commensals, by aiding bacterial migration. PMID- 8486416 TI - Reverse flux filtration: a new mode of therapy improving the efficacy of heparin induced extracorporeal LDL precipitation in hyperlipidemic hemodialysis patients. AB - In the steady state after a run-in phase of 3 months, the acute effects of 3 modifications of weekly heparin-induced extracorporeal LDL precipitation (HELP) were studied in 5 ESRD and 2 non-uremic hypercholesterolemic coronary patients. In ESRD patients (n = 29 sessions), HELP reduced LDL-cholesterol (LDL-C) (56 +/- 7%) and fibrinogen (FIB) (54 +/- 10%) by a similar percentage as compared to non uremic controls (60 +/- 4% and 61 +/- 3%, resp.; n = 5). In order to eliminate the need for extra HELP sessions in addition to the normal dialysis regimen, newly developed hardware was then used to perform combined synchronous HELP/HD (n = 12). However, premature precipitate filter plugging probably due to hyperfibrinogenemia in ESRD patients, accentuated by ultrafiltration (UF), decreased the corresponding reductions to 26 +/- 9% (LDL-C) and 34 +/- 11% (FIB). Therefore, the procedure was modified by reversing the filtrate flux through the precipitate filter membrane after 900 ml of treated plasma ("reverse flux filtration", RFF; n = 11). Thus, in RFF-HELP/HD the LDL/FIB/heparin coprecipitate was deposited on both filter membrane sides which caused a significant enhancement of the filter capacity and improved reductions to 46 +/- 14% for LDL C and 51 +/- 15% for FIB. Elution of the precipitate from the precipitate filter after the sessions showed that RFF-HELP/HD had trapped 1733 +/- 238 mg LDL-C and 8108 +/- 1876 mg FIB in ESRD patients, while HELP eliminated 1890 +/- 333 mg LDL C and only 3663 +/- 369 mg FIB in non-uremics. Filter precipitate recoveries (relative to the mass removed from the patient plasma pool) amounted to 97 +/- 18% for LDL-C and 158 +/- 67% for FIB in the ESRD group treated by RFF-HELP/HD vs. 70 and 76% in the non-uremic HELP group. Probably, passive transport of lipoproteins and FIB from the interstitium into the vascular space caused repletion of this compartment during HELP/HD where an UF induced solvent drag is effective. In summary, the new RFF-HELP/HD procedure effectively reduced LDL-C and FIB in ESRD patients who could not be adequately treated by the conventional HELP/HD system. PMID- 8486417 TI - Catecholamine infusion versus intraaortic counterpulsation at the initial phase of left intraventricular balloon pumping in the fibrillating animal heart. AB - This experimental study compares the effect of catecholamine infusion to the effect of intraaortic counterpulsation (IABP) while initiating intraventricular balloon pumping (IVBP) in the fibrillating heart. In 12 dogs IVBP started immediately after the induction of ventricular fibrillation. Intravenous adrenaline or noradrenaline (at a progressively increasing infusion rate until the systolic aortic blood pressure was 120 mm Hg) was interchanged with IABP. The systolic aortic pressure, the aortic flow and the mean left atrial pressure were, respectively, 120.4 +/- 0.5 mm Hg, 42 +/- 4 ml kg-1 min-1 and 18.7 +/- 1.2 mm Hg (x +/- SEM) ten min after initiating catecholamine infusion and 97 +/- 5 mm Hg (with a 131 +/- 4 mm Hg diastolic wave), 69.6 +/- 4 ml kg-1 min-1 and 16 +/- 1.5 mm Hg ten min after initiating IABP. The difference in aortic flow was significant (p < 0.001). The results indicate that a better aortic flow may be obtained by combining IVBP and IABP than IVBP and vasoconstrictive agents in the fibrillating heart. If IVBP, IABP and catecholamines are combined, both AF and AP may increase. PMID- 8486418 TI - Chronic in vivo function of a new ventricular assist device: the extracorporeal pulsatile assist device (EPAD). AB - An extracorporeal pulsatile assist device (EPAD) is a valveless, single chambered, pneumatically-actuated blood pump composed of a graft conduit, connecting ring, bladder, and blowmolded housing. This allows a simple and quick surgical procedure and is easily actuated with a conventional intraaortic balloon pumping console if desired. To evaluate in vivo pump functions, the EPAD was tested in calves as a left ventricular assist device for 6-24 days. The EPAD was well synchronized to the natural heart beat up to 130 bpm in the counterpulsation mode with mild systemic heparinization (active clotting time: 200-250 seconds). Heart rate, coronary flow and cardiac output were not significantly changed by on off testing. However, the pump showed promising diastolic augmentation (10.8% increase in the diastolic pressure time index) in these chronic animal experiments. PMID- 8486419 TI - Transplantation of free and microencapsulated islets in rats: evidence for the requirement of an increased islet mass for transplantation into the peritoneal site. AB - Microencapsulation of islets of Langerhans may avoid the necessity of a permanent immunosuppressive drug therapy and opens up new perspectives for xenotransplantation in the treatment of insulin dependent diabetes. In a mouse model we recently showed long-term normoglycemia after microencapsulated xenotransplantation. Since the acceptance of mice to any kind of foreign material is quite high we assume that the rat model better reflects the situation of higher mammalians or even humans. Due to the volume of the transplanted material (i.e. islets+alginate-capsule) only the peritoneal cavity can be used up to now. The quantity of islets necessary to normalize the non-fasting blood glucose level was much higher than expected and free transplants needed even a higher amount of islets than encapsulated ones (3000 encapsulated vs. 2 x 3000 non-encapsulated). Transplantation beneath the kidney capsule was successful with only 1200-1500 islets per rat proving the metabolic potency of the islets. Implantation of empty capsules did not alter the diabetic state. We conclude that the alginate matrix may act as a "spacer" creating a distance between the consuments of a lacking substrate esp. oxygen in an unfavourable environment and perhaps protect it from unspecific mediators released during the postoperative period. Our findings underline the necessity for smaller capsules that would enable us to use other transplantation sites. PMID- 8486420 TI - Tumor antigens recognized by cytolytic T lymphocytes: present perspectives for specific immunotherapy. PMID- 8486421 TI - Cytologic screening for esophageal cancer: results from 12,877 subjects from a high-risk population in China. AB - Linxian, China, has one of the highest esophageal-cancer mortality rates in the world. In 1983, esophageal balloon-cytology screening was performed to identify subjects eligible for 2 nutrition-intervention trials in Linxian; 12,877 subjects had cytology slides which were satisfactory for diagnosis. Of the 12,649 subjects with squamous-cell diagnoses, 31% were normal by Chinese cytologic criteria; 38% showed hyperplasia; 21% showed dysplasia 1; 6% showed dysplasia 2; 2% showed near cancer; and 2% showed cancer. Of the 1,471 subjects with columnar-cell diagnoses, 31% were normal; 44% showed hyperplasia; 16% showed dysplasia 1; 4% showed dysplasia 2; 2% showed near-cancer; and 3% showed cancer. Squamous dysplasia and cancer were more common among females than males, while columnar dysplasia and cancer showed male predominance. The prevalence of dysplasia and cancer of both cell types increased with age. The prevalence of squamous dysplasia was significantly higher than in earlier balloon-cytology screenings in Linxian, probably reflecting changes in cytologic classification. PMID- 8486422 TI - In situ evaluation of the relationship between epidermal-growth-factor-receptor status and tumor-cell proliferation in colon carcinomas. AB - The association between the expression of the epidermal-growth-factor receptor (EGFR) and tumor proliferation was studied in 69 resected human adenocarcinomas of the colon. EGFR was detected immunohistochemically using the monoclonal antibody (MAb) EGFRI. Tumor-cell proliferation was assessed with the MAb Ki-67 directed against a proliferation-associated nuclear antigen expressed only in proliferating cells. The percentage of Ki-67-positive tumor cells (Ki-67 index) was evaluated by the point-counting method. Forty-seven carcinomas contained detectable EGFR immunoreactivity. Statistical analysis failed to reveal correlations between the EGFR status and T, N and M stages or tumor differentiation. The mean Ki-67 index did not differ between EGFR-positive and negative carcinomas. Seven tumors contained clearly distinguishable areas with different EGFR staining intensity. In these tumors with a locally heterogeneous EGFR expression, tumor proliferation also did not correlate with EGFR immunoreactivity. These in situ observations suggest that EGFR expression may not play an important role in the growth regulation of human colonic carcinomas. PMID- 8486423 TI - Histologic grading in soft-tissue sarcomas. An analysis of 194 cases including AgNOR count and mast-cell count. AB - In order to establish a new histologic grading system for STS, we evaluated histologic prognostic factors. For this purpose, we selected 194 patients with STS: 31 in the upper extremities, 63 in the trunk, and 100 in lower extremities. All the patients were treated by surgery, followed by chemotherapy in 74 cases, radiotherapy in 11, chemotherapy and radiotherapy in 30, or no adjuvant treatment in 79. Histologic factors evaluated were mitotic count, extent of necrosis, cellularity, cellular pleomorphism, extent of myxoid change, sclerosis, non specific histologic diagnosis, counting of reaction product in silver stain for nucleolar organizer regions (AgNOR) and mast-cell counts. Univariate analysis revealed mitotic count, necrosis, cellularity, cellular pleomorphism, non specific histologic classification, AgNOR count and mast-cell count to be significantly related to prognosis. Multivariate analysis revealed that AgNOR count, cellularity and necrosis were independent prognostic factors. A new grading system was introduced: low-grade, intermediate-grade and high-grade. The survival between each group were significantly different; the 5-year-survival rate in patients of the low-, intermediate- and high-grade groups was 87%, 74% and 35% respectively. Our findings suggest that this histologic grading system may be useful for making therapeutic decisions. PMID- 8486424 TI - Cell proliferation as a long-term prognostic factor in diffuse large-cell lymphomas. AB - The relevance of cell proliferation rate--defined as the 3H-thymidine labeling index (3H-dT LI)--in predicting response to treatment (complete remission, CR), freedom from progression (FFP) and overall survival (OS) was evaluated in 86 patients with diffuse large-cell lymphoma (DLCL). The biologic variable was not associated with most of the established clinical factors, such as gender and age of the patient, performance status, B symptoms, tumor bulk, or extranodal disease, but was directly related to stage. 3H-dT LI significantly predicted short- and long-term clinical outcome. In fact, more patients with slowly proliferating DLCL reached CR and had longer median FFP and OS than patients with rapidly proliferating DLCL. Multiple-regression analysis to evaluate the relative contribution of the different biologic and clinical variables in predicting CR, FFP and OS showed that 3H-dT LI and Ann Arbor stage were the only 2 stable factors, which retained their prognostic significance even in the presence of other conventional factors, and that 3H-dT LI was the most powerful as an indicator of risk of death in DLCL patients. PMID- 8486425 TI - Appearance of amplified thymidylate synthase or dihydrofolate reductase genes in stage-IV breast-cancer patients receiving endocrine treatment. AB - We have examined the appearance of amplification of 2 genes involved in resistance to chemotherapy (thymidylate synthase, dihydrofolate reductase) in patients receiving endocrine treatment. Chronological tumor samples were obtained from breast-cancer patients with clinical stage-IV disease, using fine-needle biopsies. The presence of amplification of thymidylate synthase and dihydrofolate reductase was determined using PCR in 185 fine-needle biopsies from 37 patients. None of the initial samples of each patient showed amplification. However, in 7 of the 37 patients (19%) we detected development of gene amplification: in 2 cases of thymidylate synthase and in 5 cases of dihydrofolate reductase. Five of the 7 patients with amplification were receiving second-line endocrine treatment after failing to respond to tamoxifen. PMID- 8486426 TI - Oral contraceptives and endometrial cancer: do other risk factors modify the association? AB - The joint effect of use of combination-type oral contraceptives and other exposure factors on risk of endometrial cancer was examined in data from a multicenter case-control study conducted in 5 areas of the United States. Cases were 405 women with histologically confirmed invasive epithelial endometrial cancer first treated at one of 7 participating hospitals. A total of 297 population-based controls of similar age, race, and geographic area were selected as a comparison group. Information on exposure factors was derived from in-person interviews. Combination-type oral contraceptive (COC) use was associated with a significant reduction in risk of endometrial cancer, with an adjusted odds ratio (OR) of 0.4 (95% confidence interval 0.3 to 0.7) for ever compared to never use. Long-term (> or = 10 years) users experienced a markedly lower risk (OR = 0.2). Women who discontinued COC use > or = 20 years earlier remained at reduced risk (OR = 0.7) compared with non-users. The negative association with COC use was apparent regardless of the presence or level of several other risk factors for endometrial cancer, including age, menopausal status, parity, obesity, ever-use of menopausal estrogens, smoking history, or history of infertility. The magnitude of the negative association observed in COC users, however, was considerably diminished in women with no full-term births and in women who subsequently used replacement estrogens for 3 or more years. These results provide new evidence that the protective effect of COC use lasts for 20 or more years after use is discontinued, and highlight several sub-groups of users in whom the level of protection is attenuated by the presence of other risk factors for this disease. PMID- 8486427 TI - Prevalence of G-to-T transversions among K-ras oncogene mutations in human colorectal tumors in Yugoslavia. AB - Human colorectal carcinoma tissue sampled from 37 patients, routinely graded into Dukes' stages A, B and C and histologically examined for the level of differentiation, were analyzed for the presence of point mutations in the K-ras oncogene. Seventeen cases out of the 37 analyzed were found to have a mutation in either the 12th or the 13th codon of the K-ras gene, giving an overall frequency of mutation of 46%. The incidence of mutations in Dukes' stages A, B and C was 33, 46 and 58% respectively. Although the frequency of mutation appears to be similar to that reported for the USA population, the spectrum of point mutations in codons 12 and 13 of the K-ras gene in the Yugoslav population appears to differ significantly. G-to-T transversions make up 77% of all mutations present, with the distribution as follows: 18% at the first base and 59% at the second base of codons 12 and 13. G-to-A transitions at the second base is the only other mutation identified, occurring mainly in codon 13 in colorectal tumors of all 3 stages. PMID- 8486428 TI - HTLV-I and HTLV-II world-wide distribution: reanalysis of 4,832 immunoblot results. AB - Mapping the geographic distribution of human T-lymphotrophic virus types 1 and 2 (HTLV-I and -II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV-I and HTLV-II, we evaluated a convenience sample of 4,832 HTLV-I immunoblot results from over 140,000 samples screened for HTLV-I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV-I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV-I), type 2, p24 stronger than p19 (presumptive HTLV-II), or indeterminate (p19 and p24 weakly positive or p19 weakly positive in the presence of p21e). Geographic areas could be grouped into 4 patterns. Patterns A (> 75% type I) and B (> 75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous-drug-using and other populations in which both virus types have been reported. Pattern D (> 10% indeterminate), suggests the presence of non-specific reactivity, perhaps resulting from exposure to non-virus-related antigens or an HTLV-related virus. HTLV-I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro-populations of the Western hemisphere. HTLV-II clusters in Native American populations and among intravenous drug users. Pattern-D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types. PMID- 8486430 TI - Expression of MaTu-MN protein in human tumor cultures and in clinical specimens. AB - MaTu is a novel agent which may be of relevance in human oncogenesis, and has 2 components. One of them, the exogenous MX (coding for protein p58X), is transmissible to human fibroblasts, to HeLa and to HeLa x fibroblast (H/F) hybrids. The other component, MN, is a cellular gene. Its product, the protein p54/58N, is inducible by infecting HeLa cells with MX or by growing them in dense cultures. This p54/58N appears to be a tumor-associated antigen: it is expressed in HeLa and in tumorigenic cells (H/F-T), but not in fibroblasts or in nontumorigenic hybrid cells (H/F-N). Proteins related to p54/58N were also found on immunoblots prepared from human carcinomas of ovary, endometrium and uterine cervix, but not from normal tissues from corresponding organs or from placenta. Using genetically engineered MN protein, we developed a radioimmunoassay for MN specific antibodies, and for quantitative determination of MN proteins in cell extracts. In HeLa cells infected with MX we observed conspicuous ultrastructural alterations: formation of abundant filaments on the cell surface and amplification of mitochondria. Using immunogold-staining, we visualized the p54/58N on the surface microvilli and in the nucleus, particularly in nucleoli. PMID- 8486429 TI - Polarization of the alpha 6 beta 4 integrin in ovarian carcinomas. AB - By immunizing a BALB/c mouse with a human ovary-carcinoma cell line (IGROV1), grown intraperitoneally in nude mice, a monoclonal antibody (MAb), designated MAR6, was produced and characterized. Immunofluorescence on the immunizing cell line showed a specific labelling by MAR6 at the cell-to-cell contact points. In addition, MAR6 was found to immunoprecipitate the alpha 6 beta 4 integrin complex. Competition tests with MAbs anti-alpha 6, anti-beta 4, anti-beta 1 sub units demonstrated that the recognized sub-unit is alpha 6. Indirect immunofluorescence on various cell lines gave MAR6 as positive only on alpha 6 positive lines (IGROV1, OVCAR3, SW626, SKOV3, ME4405, Calu3, N592, MDA468, A431 and HT29). Moreover, on IGROV1 and OVCAR3 ovary-carcinoma cells, which normally grow either adhering to the culture flask or forming clumps in suspension in the medium, MAR6 selectively stained the connection points between the cells in clumps, where, in the same position, the presence of the beta 4 sub-unit, laminin and fibronectin was detected. On the contrary, the beta 1 sub-unit was distributed over the whole cell membrane. The same pattern of labelling by these MAbs was observed in 2 cases of ovarian-carcinoma cells present in ascitic fluids obtained from patients. Immunoperoxidase tests performed on cryosections of various normal tissues showed specific reactivity of MAR6 on basal or basolateral membranes of epithelial cells. On cryosections of ovarian tumors, MAR6 reactivity correlated with the degree of tumor differentiation. Indeed, in benign and well differentiated tumors, a strong basal or basolateral labelling only of cells surrounding the neoplastic nodules was found. On the contrary, on undifferentiated tumors the inner part of the tumor nodules was also progressively labelled, whereas the staining on the border was weak and discontinuous as a result of the alpha 6 sub-unit dispersion on the tumor cell surface. PMID- 8486431 TI - Uptake of the neuron-blocking agent meta-iodobenzylguanidine and serotonin by human platelets and neuro-adrenergic tumour cells. AB - The adrenomedulla-imaging agent meta-iodobenzylguanidine (MIBG) is concentrated by various tumours of neuroectodermal origin. Radio-iodinated [131I]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [131I]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine-sensitive uptake of [131I]MIBG was much slower than of [3H]serotonin, but after prolonged incubation high and serotonin equivalent uptake levels were observed. Accumulation of MIBG saturated at 10- to 100-fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuroadrenergic Uptake-I in SK-N-SH neuroblastoma and PC12 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PC12 cells, similarly to that of serotonin in platelets. However, the drug was 100-fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro-adrenergic Uptake-I, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro-adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet uptake of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro adrenergic target cells. PMID- 8486432 TI - Suppression of tumorigenicity in temperature-sensitive mutants of embryonal carcinoma cells by induction of cell differentiation at non-permissive temperature. AB - The temperature-sensitive (ts) mutants of cell differentiation derived from the mouse teratocarcinoma cell line F9, when exposed to non-permissive temperature, undergo stem-cell differentiation concomitant with a transient retardation of cell-cycle progression. By incubating these mutant strains at non-permissive temperature, we were able to study the relationship between cell differentiation and tumorigenicity. Upon exposure to non-permissive temperature, the mutant cells undergo extensive differentiation and lose their ability to initiate tumors in vivo, but retain their in vitro proliferative potential. Our data suggest that the loss of tumorigenicity is not caused by altered proliferative potential, but rather by cell differentiation. We therefore suggest that the loss of proliferative potential and the onset of cell differentiation in teratocarcinoma F9 cells are 2 independent events which can be genetically dissected, and that there is (a) crucial step(s) in the differentiation pathway at which these ts mutant cells lose their tumorigenicity. PMID- 8486433 TI - Predicting treatment retention among cocaine users. AB - Few studies have addressed treatment retention among cocaine-using samples. The current study develops and tests a model of treatment retention at the individual level, employing data from 110 cocaine users who initiated outpatient treatment. The model includes measures of extent of drug involvement, social isolation and support, motivation, and demographic characteristics. Logistic regression is used to fit a final model, which includes measures of the following: living alone, use of multiple substances prior to treatment, length of cocaine use, and external motivation. Treatment implications and directions for further research are discussed. PMID- 8486434 TI - Treating chemical dependency: the need for including the family. AB - Regression analysis was used to test Family Systems Therapy as a fruitful approach in chemical dependency treatment. Results indicate that the concerned person's perceptions of family life are critical in determining whether a family completes therapy or terminates early. Using both family and individual level variables, the significance and direction of the coefficients are consistent with the Family Systems Therapy model. Results support the importance of including the family in chemical dependency treatment. PMID- 8486435 TI - Misuse and legend in the "toad licking" phenomenon. AB - Between 1988 and 1992 a new illicit drug experience arrived on the cultural scene in the United States, Canada, South and Central America, and Australia. The media created a frenzy of misinformation in reporting on the latest drug craze which was termed "toad licking". The uses of bufo toad secretions have occurred throughout history in a variety of cultural milieus. These are explored as a backdrop to contemporary drug use/misuse issues. At the interpersonal and social level, media exposure helped create and maintain the use/misuse phenomenon, turning a fairly obscure activity into a potential epidemic. PMID- 8486436 TI - Ethnic and gender differences in drug users' perceived need for treatment. AB - Little is known about ethnic and gender variation in drug users' perceived need for treatment or about the predisposing factors that might account for such variation. Among 1,170 drug-using arrestees in Los Angeles, perceived need for treatment is positively related to these predisposing factors: self-reported drug dependence, attitude toward treatment for drug use, and occurrence of drug related problems other than dependence. Self-reported drug dependence is higher among women and accounts for the greater perceived need reported by women. Hispanics are less likely to perceive a need for treatment. Among daily drug users, both Hispanics and Africans Americans are less likely to do so. These ethnic differences are not explained by self-reported drug dependence or any other predisposing factor. Implications for treatment referral, intake, and counseling are discussed. PMID- 8486437 TI - Perceptions of the causes of drug use in a series of articles in The International Journal of the Addictions. AB - There is now considerable evidence of historical variation in the definition of problem drug use. Less well studied has been contemporary variations in the perception of drug use. To remedy this, an examination of a series titled "From Theory to Practice: The Planned Treatment of Drug Users," published in The International Journal of the Addictions, was undertaken. The analysis shows little agreement on the causes of drug usage. The implications of this disagreement for policy is illustrated by showing how different perceptions of the causes of drug use imply different ways of responding to that use. PMID- 8486438 TI - Social networks and support mechanisms for people with mild intellectual disability in competitive employment. AB - Participant observation techniques were used to examine the social networks and the social support mechanisms of nine subjects with a mild intellectual disability working in competitive employment settings. Results indicated that the social networks of this group of people lacked complexity with few interconnections among the network nodes. The major sources of social support emanated from the family and from organizations catering for people with disabilities. While subjects perceived considerable social support within the workplace, this support was restricted to the workplace and in general did not extend beyond it. Implications of the findings of the study for ensuring the adequacy of social support both within and beyond the workplace for this group of people are discussed. Additionally, the need for the development of a theory or model of social support as it pertains to people with a mild intellectual disability employed in competitive employment settings is advocated. PMID- 8486439 TI - Rehabilitation innovations in Central America. AB - In an extensive qualitative research project sponsored by the Partners of the Americas (32 professional and lay people from Panama, Costa Rica, Nicaragua, Honduras, El Salvador, Guatemala, Belize, the United States and the Dominican Republic) employment opportunities were examined for disabled youth in Central America. Despite economic and attitudinal barriers field researchers found innovations in financing, special education and rehabilitation programming, job development and job placement alternatives for those who live with disability in Central America. PMID- 8486440 TI - Early intervention for children with developmental disabilities: manifesto of the Eurlyaid working party. AB - Eurlyaid is a working party of the European Community (EC). It consists of experts and representatives of parents' associations from the various member states involved in early intervention for children who are disabled or at risk of developmental disabilities. Starting from the growing recognition of the importance of early identification and intervention Eurlyaid aims to contribute to the development of a common EC policy and legislation. Here we describe a comprehensive framework for early intervention, presented as a preliminary manifesto. First of all the Manifesto gives a definition of key concepts, delineates the target group and states the rationale behind, and the content, of early intervention. Secondly, we present the conditions and demands necessary to attain the best quality early intervention, and make a number of recommendations. With an EC grant, Eurlyaid is able to continue its activities as part of ALEFPA Europe, a so-called non-governmental organization (NGO). PMID- 8486441 TI - Labour market conditions and the rehabilitation process. PMID- 8486442 TI - New technology training for people with disabilities in Great Britain. PMID- 8486443 TI - Vocational rehabilitation of young adults with a disability of one arm or hand. PMID- 8486444 TI - Evaluating a rehabilitation co-ordinator service for personal injury claimants. PMID- 8486445 TI - Individuals with psychiatric disabilities in adult homes: monitoring changes over time. PMID- 8486446 TI - Self-awareness of people with mental handicap. PMID- 8486447 TI - Facilitating conversation for non-speaking people with multiple handicaps. PMID- 8486448 TI - A model for touch technique and computation of adequate cane length. PMID- 8486449 TI - Employers' attitudes toward employing people with mental handicap. PMID- 8486450 TI - Attitudes and words referring to mental handicap. PMID- 8486451 TI - Prior history of back pain in patients with compensable and non-compensable injuries. PMID- 8486452 TI - Current concepts in electron microscopy. PMID- 8486453 TI - Diagnostic high-resolution ultrasound in dermatology. PMID- 8486454 TI - Dermatoepidemiology. Part I: Epidemiologic methods. PMID- 8486455 TI - In vivo cutaneous surface microscopy: revised nomenclature. PMID- 8486456 TI - Vaccine therapy in the treatment of melanoma. PMID- 8486457 TI - Acute febrile neutrophilic dermatosis (Sweet's syndrome). AB - BACKGROUND: Sweet's syndrome is well recognized and not infrequently diagnosed in Spain; however, the range of clinical and pathologic expression may not have been fully realized. METHODS: We reviewed 30 consecutive Spanish cases of Sweet's syndrome diagnosed in our department from 1979 to 1990, with special attention to clinical and histopathologic findings. RESULTS: Distinctive clinical features in our series included oral mucosa lesions in four patients (13%), development of pathergy phenomenon in one case, concurrent nodular lesions resembling erythema nodosum on the limbs in nine cases (30%), and lung involvement in two patients. Infectious disease and drug treatment were recorded as possible triggering factors of Sweet's syndrome in eight and seven patients respectively. Associated underlying systemic disorders were present in 15 (50%) of our patients. The most frequent associations were hematologic neoplasia in four patients, solid neoplasia in two, and chronic idiopathic inflammatory bowel disease in three patients. Dressler's syndrome and sicca syndrome were found in one patient each. Histopathologic studies of skin biopsy specimens obtained at presentation disclosed typical features of Sweet's syndrome in all cases. Epidermal involvement, with variable degrees of spongiosis, exocytosis of polymorphonuclear leukocytes and keratinocyte necrosis, was a prominent feature in 83% of biopsy specimens. CONCLUSIONS: Further characterization of the clinicopathologic spectrum of Sweet's syndrome is necessary as the recognition of the full spectrum of this syndrome will improve our diagnostic abilities and provide a solid clinical basis for prospective studies that allow dissection of the intricate patho-mechanisms involved in this fascinating disorder. PMID- 8486458 TI - Ultrastructural study of vitiligo. AB - BACKGROUND: Vitiligo is a relatively common skin disease characterised by development of patchy depigmented macules. A comparative ultrastructural study was undertaken between early developing (2-6 months duration) and long standing (1-5 years duration) lesions of vitiligo in a series of ten patients. METHODS: Skin biopsy specimens from the ten patients were fixed, stained, and examined under an electron microscope. RESULTS: No melanocytes were found in the sections taken from long standing lesions. The sections from early lesions showed junctional melanocytes exhibiting various cellular abnormalities. The epidermal keratinocytes were normal in all sections; however, some sections from the periphery of early lesions exhibited minor degenerative changes. CONCLUSIONS: We can assume that because of the absence of melanocytes in long standing lesions, repigmentation may occur only from the melanocytic reservoir in the hair follicles. Repigmentation may also occur in lesions of short duration by reactivation of melanocytes present in the area, so an attempt should be made to treat vitiligo lesions in their early stage. PMID- 8486459 TI - Heparin-associated thrombocytopenia and thrombosis (HATT) presenting with livedo reticularis. AB - BACKGROUND: Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequently encountered syndrome characterized by ischemic necrosis of soft tissue and vital organs following anticoagulation with heparin. The syndrome is thought to be due to heparin-dependent platelet aggregation and thrombosis, which is mediated by pathologic immunoglobulins. CASE REPORT: A 60-year-old man developed truncal livedo reticularis and ischemic necrosis of the left foot associated with thrombocytopenia, disseminated intravascular coagulopathy (DIC), and microangiopathic hemolytic anemia during intravenous heparin therapy. Skin biopsy from an area of livedo reticularis revealed fibrin thrombi in dermal blood vessels, which is characteristic of HATT. The diagnosis of HATT promoted discontinuation of heparin and a resulting rapid resolution of the livedo reticularis and hematologic abnormalities. No other potential causes of DIC were identified, and, other than stopping heparin, no specific therapy was employed. CONCLUSIONS: Periodic monitoring of platelets should be performed on all patients receiving treatment with heparin, as early detection of heparin-induced thrombocytopenia followed by discontinuation of the drug may prevent life threatening thrombotic complications. HATT should be included in the differential diagnosis of patients with livedo reticularis that occurs during heparin therapy. PMID- 8486460 TI - Multiple agminated pigmented Spitz nevi (mimicking acral lentiginous malignant melanoma and dysplastic nevus) in an African-American girl. AB - BACKGROUND: Reed's nevi are distinguished from Sptiz tumors by their significant melanogenesis and growth pattern. They may be confused with melanoma on clinical and histologic grounds. CASE REPORT: An unusual case in which multiple agminated Reed's nevi mimicked acral lentiginous malignant melanoma in an African-American girl is presented. A critical review of the literature is presented to assist in the diagnosis. CONCLUSIONS: Awareness of this entity and of its possible clinical presentations and judicious application of conventional hematoxylin-eosin microscopic criteria remain the most useful methods to bring the correct diagnosis in most instances. Mutilating or excessive surgery may be avoided for most cases of pigmented spindle and epithelioid cell nevus. PMID- 8486461 TI - Peripheral blood lymphocyte imbalance in Koreans with active vitiligo. AB - BACKGROUND: An immune-mediated destruction of melanocytes is the most popular current theory of vitiligo. There have been a few published reports on the assessment of lymphocyte population in vitiligo, and they showed mixed results. The purpose of our investigation was to assess peripheral lymphocyte subpopulations in Koreans with actively spreading vitiligo. METHODS: Fifty patients with actively spreading vitiligo and 30 normal persons were studied for peripheral blood lymphocyte imbalance using flow cytometry. The percentages of total T-lymphocytes, B-lymphocytes, helper T cells, suppressor T cells, and natural killer cells were evaluated with the use of CD3, CD19, CD4, CD8, and CD16 monoclonal antibodies, respectively. RESULTS: The mean value of helper T cells showed a significant difference between the two groups with the value being 38.2% in patients and 43.5% in control subjects. Seventeen of the 50 patients showed reversed helper/suppressor T cell ratio, whereas only 1 of 30 control subjects showed reversed ratio. There was a statistically significant difference in the mean percentage of helper T cells and suppressor T cells between generalized vitiligo patients and control subjects. The percentage of B cells in patients with recent onset less than 1 year was higher than control subjects and patients with late onset. The mean percentage of natural killer cells was increased significantly in patients with negative autoantibody test. CONCLUSIONS: The present data show that immunologic abnormalities, both cellular and humoral, are involved in the pathogenesis of vitiligo. PMID- 8486462 TI - Margin assessment of selected basal cell carcinomas utilizing laser Doppler velocimetry. AB - BACKGROUND: Basal cell carcinomas (BCC) have increased vasculature, therefore, blood flow within the tumor may be greater than normal surrounding skin. We attempted to detect the difference in blood flow between the tumor and uninvolved surrounding skin utilizing laser doppler velocimetry (LDV). METHODS: Ten patients with 14 BCC were studied. Using LDV, we calculated the size of the tumor based on margin assessment as predicted by the measured difference in blood flow and compared this size with the clinically predicted size and the size of the defect after Mohs micrographic surgery (MMS). RESULTS: Clinical evaluation of tumor size prior to MMS did not correlate with the size of the surgical defect after MMS; however, correlation was found between the predicted size of the tumor as determined by LDV and the defect after MMS. CONCLUSIONS: Tumor size of BCC as predicted by measured differences in blood flow using LDV correlated with the size of the surgical defect after MMS. This suggests that LDV was able to detect the difference in blood flow between the tumor and uninvolved surrounding skin. PMID- 8486463 TI - Natural history of a superficial spreading melanoma. PMID- 8486464 TI - Malignant melanoma in a tattoo. PMID- 8486466 TI - The dermatology society historian. PMID- 8486465 TI - Granulocytic sarcoma (chloroma) of chest wall at site of Hickman line. PMID- 8486467 TI - Fibrin cuff lysis in chronic venous ulcers treated with a hydrocolloid dressing. AB - BACKGROUND: Pericapillary fibrin cuffs (PFC) are a recognized part of the pathology of venous stasis ulcers. A hydrocolloid dressing capable of lysing wound surface fibrin was tested in venous ulcers for its capacity to lyse pericapillary fibrin below the wound surface. METHODS: Tissue biopsies from the rims of 19 venous ulcers were evaluated for thickness of shallow and deep dermal PFCs before and after treatment with DuoDERM covered by Unna's boot and a compression bandage (DD+UB; n = 9) versus the same treatment without the hydrocolloid dressing (UB; n = 10). Frozen sections of all biopsies were stained with an immunofluorescent antibody to fibrin for rating of PFC thickness. Separate sections were stained with hematoxylin and eosin to assess capillary frequency, histopathology, and inflammation. All ratings and pathology assessments were performed blinded to treatment conditions. RESULTS: Both deep and shallow PFCs were reduced in 89% of ulcers treated with DD+UB versus 40% of ulcers treated with UB (alpha < 0.04). No other significant differences in inflammation, histopathology, or capillary frequency were observed. CONCLUSIONS: Treatment with DD+UB reduced PCFs in twice the number of ulcers than UB alone in 1 week. This is the first scientific documentation that a topical wound dressing could reduce the pathophysiology associated with venous ulcers, beyond the known beneficial effect of graduated compression. Not all hydrocolloid dressing are fibrinolytic, so this effect may not generalize to other dressings. PMID- 8486468 TI - Pemphigus vulgaris after electrosurgery (thermal-heat therapy) of a basal cell carcinoma. PMID- 8486469 TI - Amoxicillin cross reacts with penicillin on first exposure. PMID- 8486470 TI - The vacuolar H(+)-ATPases: versatile proton pumps participating in constitutive and specialized functions of eukaryotic cells. PMID- 8486471 TI - Molecular and kinetic aspects of sodium-calcium exchange. PMID- 8486472 TI - [The hypersensitive bronchial system. Significance for prognosis inhibition of progression of chronic obstructive respiratory tract diseases]. PMID- 8486473 TI - [Inhibition of progression of decreasing bone mass and manifest osteoporosis]. PMID- 8486474 TI - [Early chronic polyarthritis. Possibilities and limits of inhibition of joint destruction]. PMID- 8486475 TI - [Inhibition of the progression of chronic liver diseases]. PMID- 8486476 TI - [Crohn disease. How can short bowel syndrome be prevented?]. PMID- 8486477 TI - [Inhibition of the progression of renal failure in glomerular diseases]. PMID- 8486478 TI - [Systemic lupus erythematosus]. PMID- 8486479 TI - [Young patient with hypotension, constipation and urinary retention]. PMID- 8486480 TI - [Low platelet count without manifest disease]. PMID- 8486481 TI - [How should serologic findings in borreliosis be evaluation (for example high antibody titer in remitted symptoms)?]. PMID- 8486482 TI - [Hypercalcemia]. PMID- 8486483 TI - The influence of clinical history on visual search with single and multiple abnormalities. AB - RATIONALE AND OBJECTIVES: Facilitation of detection by clinical history generally has been found with a single abnormality per image but not with multiple abnormalities. Multiple abnormalities per image can occasion a "satisfaction-of search" effect in which detection of one lesion is reduced in the presence of other distant lesions. Our experiment studied the combined effect of multiple abnormalities and clinical history on accuracy. METHODS: Detection of native lesions was measured 1) with histories suggestive of the native abnormality; 2) with these histories and added simulated pulmonary nodules; and 3) with the same added nodules and histories suggestive of metastatic disease. These conditions also were compared with those of a previous experiment that were similar but included no history. RESULTS: Detection was substantially improved for appropriately prompted abnormalities even in the presence of a pulmonary nodule. In fact, satisfaction of search was not found in the presence of an appropriate history. Detection of unprompted abnormalities was unchanged when prompts indicated other abnormalities actually present. Prompted abnormalities were detected earlier in search. CONCLUSIONS: History appears to direct perceptual resources to the prompted abnormalities, thereby alleviating satisfaction of search. The presence of nodules yielded a small but consistent reduction in total search time for searches involving false responses, suggesting that satisfaction of search may depend more on reduction in search time than had been indicated by previous research. PMID- 8486484 TI - Invasive lobular carcinoma. Imaging features and clinical detection. AB - RATIONALE AND OBJECTIVES: Mammographic findings and method of detection of 52 cases of invasive lobular carcinoma (ILC), the second most common breast carcinoma, are reported. METHODS: Preoperative mammograms and clinical records of all patients with ILC not associated with a second mammary carcinoma (other than lobular carcinoma in situ) from 1979-1991 at the authors' institution were retrospectively reviewed. RESULTS: Abnormal mammographic findings were present in 48/52 (92%) and included irregular spiculated masses (33/52, 63%), asymmetric densities (7/52, 13%), architectural distortion (5/52, 10%), microcalcifications (2/52, 4%), and well circumscribed masses (1/52, 2%). The mean mammographic diameter was 2.1 cm. The tumor was most often best visualized in the craniocaudal projection. At the time of diagnosis, 54% of women had coexistent suggestive breast physical findings and 35% had metastatic carcinoma in axillary lymph nodes. CONCLUSIONS: The infrequency of microcalcifications in pure ILC may hinder mammographic detection and contrasts markedly with ductal carcinoma. Mammography and breast physical examination play complementary roles in the detection of ILC. PMID- 8486485 TI - Susceptibility effects of bone trabeculae. Quantification in vivo using an asymmetric spin-echo technique. AB - RATIONALE AND OBJECTIVES: The authors assessed the capability of magnetic resonance imaging in measuring bone mineral density in vivo. METHODS: Using the in-phase asymmetric spin-echo technique, the susceptibility effect (T2*susceptibility) was measured in lumbar vertebrae in vivo. Calcium density was measured with single energy quantitative computed tomography scan. The values of the susceptibility effect were correlated with calcium density. RESULTS: A statistically significant positive correlation was observed between signal loss due to susceptibility-induced inhomogeneity and the calcium density in the region of interest. The change in 1/T2*susceptibility per unit change in density was 0.114 seconds-1/mg/cm3. T2*susceptibility was 14.3 mseconds in volunteers and 17.4 mseconds in postoophorectomy patients. CONCLUSIONS: To some extent, quantification of bone density is possible using magnetic resonance imaging; however, the relatively wide dispersion of the susceptibility effect, plotted against the calcium density in the axial skeleton, indicates that other factors, such as the three-dimensional structure of bone trabeculae, may play important roles in determining magnetic resonance parameters. PMID- 8486486 TI - Effect of clinical history on the interpretation of chest radiographs in childhood bronchiolitis. AB - RATIONALE AND OBJECTIVES: This study assesses the effect of a clinical history of "bronchiolitis" versus "well child" on the interpretation of pediatric chest radiographs. METHODS: Radiologists reviewed radiographs previously identified as "definite bronchiolitis," "equivocal bronchiolitis," "definite normal," and "equivocal normal." They were asked to identify features of bronchiolitis and give a confidence level for their diagnosis. A correct clinical history of "bronchiolitis" or a "well child" was provided for all definite and half the equivocal radiographs. The other half of the equivocal radiographs were matched with incorrect histories. RESULTS: Given normal radiographs with a history of bronchiolitis, radiologists reported more features of bronchiolitis with increased confidence and also more features. CONCLUSIONS: The results suggest that the effect of history is not simply to provide additional confirmatory information, thereby increasing the diagnosis rating, but rather to change the interpretation of features, to the extent that features apparently are seen even on normal radiographs. PMID- 8486487 TI - Detection of experimental rat liver tumors by contrast-assisted ultrasonography. AB - RATIONALE AND OBJECTIVES: The authors characterized the effect of intravenous lipid-coated microbubbles (LCMs) on the echogenicity of malignant liver tumors. METHODS: Novikoff hepatoma cells were inoculated into the livers of 16 anesthetized Sprague-Dawley rats. Sonograms were obtained weekly after tail-vein injection with either 0.2 mL/kg LCMs or saline control. RESULTS: A statistically significant difference in the signal-to-noise ratio (SNR) was observed between the group that received LCMs (10 rats) and the group that received saline (6 rats) (P < .01). The effect persisted for 30 minutes after contrast injection. Selective leakage and accumulation of LCMs into the tumor tissue itself was confirmed histologically using lipid-specific counterstains. CONCLUSIONS: Intravenous injection of the LCM contrast agent produces a rapid increase in the echogenicity of the experimental Novikoff tumor in the rat liver. PMID- 8486488 TI - Sodium-calcium balance in nonionic contrast media. Effects on the risk of ventricular fibrillation in the isolated rabbit heart. AB - RATIONALE AND OBJECTIVES: During coronary arteriography the blood is replaced for a short period of time with a contrast medium (CM) solution. The CM may cause a risk of arrhythmias and ventricular fibrillation (VF). Previous investigations have shown that the addition of small amounts of sodium (10-30 mmol/L) to nonionic CM may decrease the risk of VF from these media. Calcium addition to nonionic CM may reduce a negative inotropic effect. In the current investigation, the changed risk of VF from nonionic CM with 19 to 30 mmol/L NaCl was studied when the media also contained calcium or calcium and magnesium. METHODS: An isolated rabbit heart model was used. The risk of arrhythmias and VF from the nonionic monomer iohexol and the nonionic dimer iodixanol containing 19 to 30 mmol/L NaCl with 0 to 2.5 mmol/L calcium as CaCl2 was studied. In the series with iodixanol, 0 to 0.95 mmol/L MgCl2 also was added to the solutions with sodium and calcium, but the role of magnesium was not especially evaluated in the investigation. RESULTS: Nonionic CM with small amounts of NaCl (19-30 mmol/L), without calcium or with calcium at the level of 0.05 to 0.3 mmol/L, caused the lowest risk of VF. When relatively higher additions of calcium reached the physiologic concentration of 2.5 mmol/L, the CM caused a greater risk of arrhythmias and VF. CONCLUSIONS: When calcium is added to a nonionic CM, the concentration of calcium must be balanced against the NaCl concentration to minimize the risk of VF. Excessive calcium concentration will increase the risk of VF. PMID- 8486489 TI - Electrocautery of the tract after needle biopsy of the liver to reduce blood loss. Experience in the canine model. AB - RATIONALE AND OBJECTIVES: Bleeding is the most common complication of needle biopsy of the liver. This study was designed to assess the feasibility of using unipolar electrocautery to decrease bleeding. METHODS: Under general anesthesia, the livers of eight dogs were surgically exposed. A mean of 15 biopsies was obtained with 18-gauge needles from each liver by alternating biopsies without and with electrocautery. Cautery was performed by applying radiofrequency energy at 25 watts (6 animals) or 125 watts (2 animals) to the needle as the needle was withdrawn from the liver. Blood loss was measured by applying preweighed sponges to the biopsy site, then reweighing them after use. Biopsy specimens were examined by light microscopy. RESULTS: The mean (+/- SD) blood loss was 0.44 g (+/- 1.36 g) with electrocautery and 1.47 g (+/- 2.23 g) without electrocautery (P < .01). No thermal injury was noted in the biopsy specimens when cautery was applied at 25 watts. CONCLUSIONS: The application of radiofrequency current to the biopsy needle after liver biopsy is a feasible and effective method to reduce blood loss in our canine model. PMID- 8486490 TI - Digital radiography versus conventional radiography for the detection of a skull fracture under varying exposure parameters. AB - RATIONALE AND OBJECTIVES: The effect of varying exposure parameters on the detectability of a fracture with digital and conventional radiography were examined. METHODS: A macerated fractured skull was imaged by film-screen radiography (FSR) and digital storage phosphor radiography (DR) with various exposure values. Five radiologists traced the course of a fracture line. The length of the fracture was reported and the results were analyzed by Student's t test for paired samples. RESULTS: At 35% of the conventional radiation dose, the standard DR screen displayed an average of 48% of the fracture length. The difference from the conventional image (45%) was not significant in this case. An increase of the dose to ten times the conventional dose (250 mAs) yielded no significant improvement in the detectability of the length of the fracture (51%). CONCLUSIONS: This experiment shows that with use of the DR with the standard screen, a dose reduction of approximately 35% appears to be possible without any resulting loss of image quality compared to FSR. Use of the high resolution screens should be avoided, since they require a higher incident image dose than standard screens without offering any diagnostic advantages. The image dose of digital radiographs can be roughly estimated based on the digital device sensitivity value. As a rule, the sensitivity value should range between 100 and 200. PMID- 8486491 TI - Whole lung sections for computed tomographic-pathologic correlations. Modified Gough-Wentworth technique. AB - RATIONALE AND OBJECTIVES: High-resolution computed tomography of the lung has been advocated in the evaluation of interstitial lung diseases and emphysema. To provide material for correlations with gross pathology and macroscopic quantitation of emphysema, the authors have shortened and simplified the Gough Wentworth technique. METHODS: The method permits more precise correlation of cross-sectional images and pathologic specimens and is less time-consuming. RESULTS AND CONCLUSIONS: This modified method can be routinely performed in a clinical laboratory of pathology and provides paper-mounted whole lung sections within four days. The sections are protected by a transparency film. PMID- 8486493 TI - Five-year combined diagnostic radiology/nuclear medicine residency. PMID- 8486492 TI - Evaluation of the postsurgical esophagus after partial esophagogastrectomy for esophageal cancer. Normal postoperative appearance and complications. PMID- 8486494 TI - Abdominal wall mass in a pregnant woman. AB - Abdominal fibromatosis should be considered in female patients of childbearing age who present with a mass arising from the abdominal musculature, particularly if the mass becomes evident during or immediately after gestation. Magnetic resonance imaging, with its multiplanar imaging capabilities, is useful in characterizing soft tissue tumors and in defining the extent of tumor involvement of adjacent structures. PMID- 8486496 TI - A report from the American Board of Radiology. PMID- 8486495 TI - Apples and oranges. PMID- 8486497 TI - Remedial program for diagnostic radiology residents. AB - OBJECTIVES: We describe a 1-year remedial program for radiology residents with deficiencies in basic medical sciences that cause difficulty in the understanding and application of basic radiologic principles. METHODS: Six of 107 residents participated in the remedial program at separate times during an 8-year period. The design of the remedial program was based on the following: 1) reassignment to first year basic radiology rotations with 1-year delayed advancement to the subspecialty rotations; 2) comprehensive radiology texts that contain a detailed review of related embryology, anatomy, physiology and pathology; 3) instruction in the study of the texts; and 4) repetitive learning accomplished by intermittent reassignment of rotations in which difficulty was demonstrated. Resident performance was evaluated by correlation of monthly written faculty evaluations, the results of the American College of Radiology Intraining Examination, and the American Board of Radiology (ABR) written and oral examinations. RESULTS: During the period of remediation, faculty evaluation revealed improved performance in all six residents from below-average ratings (mean = 2.3) to above-average and superior ratings (mean = 8.3). These results were correlated with the American College of Radiology Intraining Examination scores, which improved from the lowest quartile (range 0% to 28%) to the highest (range 78% to 99%). Each resident successfully passed the ABR written and oral boards on the first attempt. Two additional residents who were offered but did not accept remediation eventually dropped out of the program or repeatedly failed the written ABR examination. CONCLUSIONS: Ultimately, strengthening basic medical science knowledge facilitated interpretation of radiographs by enabling the integration of basic radiologic and scientific principles and understanding the underlying basic medical, radiologic, and clinical significance. PMID- 8486498 TI - Evaluation of resident applicants by letters of recommendation: a comparison of traditional and behavior-based formats. AB - RATIONALE AND OBJECTIVES: Traditional, narrative letters of recommendation solicited by medical students applying for radiology residency are widely used as a selection tool. Letters of recommendation are considered a source of reliable information about the attitudes and behaviors (non-cognitive variables) of the resident applicant. However, in many instances, this information is not present or is highly encoded and cannot be extracted. This study attempted to document the deficiencies of traditional letters of recommendation and determine the effectiveness of a structured letter of recommendation in obtaining information regarding noncognitive variables. METHODS: One hundred thirteen randomly selected letters of recommendation were analyzed by two radiologists with experience in residency selection. Deficiencies in inclusion of information or the ability to extract information about noncognitive variables were documented. A standard behavioral assessment was sent to the writers of these letters of recommendation and these results tabulated. RESULTS: The traditional letters of recommendation were frequently deficient in data regarding the noncognitive variables. In letters that contained such data, two experienced reviewers could not reliably extract the information. The structured form produced clearly identifiable information about the letter writer's assessment of noncognitive variables. CONCLUSIONS: Traditional letters of information are frequently deficient in data regarding noncognitive variables. A standardized statement is effective in eliciting information on noncognitive variables related to applicant performance. PMID- 8486499 TI - Late bloomers. PMID- 8486500 TI - Magnetic resonance imaging contrast agents. Design and physicochemical properties of gadodiamide. PMID- 8486501 TI - Preclinical safety assessment and pharmacokinetics of gadodiamide injection, a new magnetic resonance imaging contrast agent. AB - In a wide range of preclinical studies of gadodiamide injection (Omniscan, Sanofi Winthrop, New York, NY, and Nycomed AS, Oslo, Norway), the pharmacokinetics of the compound have been delineated and its safety demonstrated. The pharmacokinetic behavior of gadodiamide was consistent with its extracellular distribution. Its half-life in rats, rabbits, and monkeys was short, 18, 38, and 75 minutes, respectively. Gadodiamide was shown to be excreted rapidly, primarily through the kidneys. In rats, 94% of the administered dose was excreted in the urine within the first 24 hours after administration. Approximately 1% to 4% appeared in the feces during the same period. Gadodiamide injection has been shown to have a remarkably low acute lethal toxicity, superior to that of gadopentetate dimeglumine injection (Magnevist, Berlex Laboratories, Wayne, NJ, and Schering AG, Berlin, Germany) or gadoterate meglumine (Dotarem, Laboratoire Guerbet, Aulnay-Sous-Bois, France). In comparison with gadopentetate dimeglumine injection, gadodiamide injection had fewer effects on cardiovascular and hemodynamic function after rapid intravenous injection in anesthetized dogs and, in vitro at high concentrations, on erythrocyte fragility and arterial wall tension. The lesser effects might be attributable, at least in part, to the lower osmolality of gadodiamide injection, although it remains to be seen whether this will translate into any advantage for gadodiamide injection at the lower doses used for imaging procedures in patients. Similar to all known intravenously administered diagnostic imaging agents, gadodiamide injection produces vacuolization of the proximal tubular cells in the kidney, without any change in renal function. However, the single-dose threshold for this effect is greater than 0.5 mmol/kg in the rat; even after a dose of 10 mmol/kg, the vacuolization was only "moderate" in degree and was shown to have regressed partially during the 7 days after administration. In monkeys, administration of 0.25 mmol/kg daily for 28 days had no effect on the kidney, thus providing reassurance of the wide margin of safety for any effect of this compound on the kidney. Although intended for single administration in patients, gadodiamide injection has been studied extensively in a range of subchronic studies in rats and monkeys. The compound was well tolerated in monkeys even when administered at doses up to 1.25 mmol/kg daily for 28 consecutive days. In rats, significant toxicity occurred only at high doses, particularly in male animals, and the pattern of toxicity (involving the stomach, testes, and skin) suggested a disturbance of zinc metabolism. Gadodiamide injection produced no significant irritation when administered by a variety of intravascular and extravascular routes. PMID- 8486502 TI - Current status of enhanced magnetic resonance imaging in neuroradiology. PMID- 8486503 TI - Gadodiamide injection. First human experience with the nonionic magnetic resonance imaging enhancement agent. AB - The safety, tolerance, and pharmacokinetics of gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York, NY) were evaluated in an open, ascending-dose study in 20 healthy male volunteers. Gadodiamide injection was administered intravenously at doses of 0.05, 0.1, 0.2, and 0.3 mmol/kg. Mild adverse events were experienced by nine subjects. These events included, but were not limited to, light-headedness, dizziness, and perversion of taste or smell. There was one occurrence of injection-associated discomfort that resolved within seconds. Vital sign and electrocardiogram measurements did not show any clinically relevant changes. There were no clinically significant changes in laboratory parameters, but minor transient elevations in serum iron were detected. These elevations typically occurred 8 and 48 hours after administration of gadodiamide injection and were not dose related. The pharmacokinetics of gadodiamide injection were evaluated in the 0.1-mmol/kg and 0.3-mmol/kg dose groups with the serum time-concentration data fitted to an open two-compartment model and the urine time-concentration data fitted to a one-compartment model. The serum elimination half-life was approximately 70 minutes, and urinary recovery was greater than 95% by 72 hours after administration. PMID- 8486505 TI - Common problems and cooperative solutions. Organizational activity in evolutionary studies, 1936-1947. PMID- 8486504 TI - Use of the magnetic resonance contrast agent gadodiamide in the central nervous system. Results of a multicenter trial. AB - To investigate the safety and efficacy of the low-osmolar, nonionic contrast agent, gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York, NY), for magnetic resonance imaging (MRI) of the head and spine, a multicenter study involving 439 patients was done at 15 centers as part of a Phase II/III clinical trial. Unenhanced MRI scans were obtained after which the patients were injected with 0.1 mmol/kg gadodiamide, and the MRI was repeated. The patients' vital signs were monitored, and laboratory studies were conducted. Neurologic status was examined before and after the study. The images were evaluated for contrast enhancement. No patient had any significant adverse event or serious change in clinical status. Abnormalities were found in 80% (351) of all patients studied, and it was found that, in 75% (266) of these, the postgadodiamide injection images were improved or facilitated visualization of lesions compared with preinjection images. The investigators believe that, based on the results of this study, gadodiamide injection is safe and effective for imaging the head and spine. They suggest that future studies further assess and compare the safety parameters of gadodiamide injection with those of other nonionic and ionic gadolinium ligands. PMID- 8486506 TI - Exteroceptive silent periods of temporalis muscle activity: correlation with neuropsychological findings. AB - The latency and duration of the early (ES 1) and late (ES 2) exteroceptive silent period of temporalis muscle activity were determined in 51 neurological patients. We investigated whether these electrophysiological parameters correlated with neuropsychological variables of the patients using standardized scores for personality index, state of well-being and physical symptoms. There were no correlations between personality traits and the electrophysiological parameters, while we found significant correlations between the duration of ES 2 and momentary psychological and physical well-being variables. Moreover, the score of the momentary well-being item 'general feeling of well-being' was demonstrated to moderate significantly the ES 2 duration (P = 0.018). Therefore, neuropsychological factors prove to be of great relevance to the exteroceptive silent periods of temporalis muscle activity. PMID- 8486507 TI - Migraine: an alternative in the diagnosis of unclassified vertigo. AB - Vertigo and unsteadiness are frequent reasons for medical consultation. In some cases, these symptoms remain unclassified. The association of equilibrium disorders with migraine is often mentioned in literature. Seventy-two cases of unclassified vertigo were studied in order to ascertain the prevalence of migraine in patients affected by recurring episodes of vertigo from undetermined causes, and attempting to establish a possible relationship with migraine. Characteristics of the vertigo and the headache, were evaluated by clinical history and examination, electronystagmogram (ENG), electroencephalogram (EEG), computerized tomography scanning (CT) and/or magnetic resonance imaging (MRI). In the group of patients studied 50% suffered from headache, and 32.8% fulfilled the diagnostic criteria of migraine. Results suggest that only a thorough clinical history would be able to give enough information to establish the diagnosis of migraine in these patients. These observations imply an alternative diagnosis to be taken into account when a case of unclassified vertigo is evaluated. PMID- 8486508 TI - Vestibulo-ocular reflex in migraine patients: the effect of sodium valproate. AB - We studied vestibulo-ocular reflex measurements in a group of 12 patients suffering from migraine without aura and evaluated the effect of sodium valproate given as prophylactic migraine therapy. The study was randomized, double blind and placebo controlled, with a crossover design. The horizontal vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration test at 0.01, 0.02, 0.04, 0.08 and 0.16 Hz using a computerized rotatory chair system. No abnormalities were found for the vestibulo-ocular reflex gain, phase and asymmetry at each of the frequencies examined during the placebo treatment. These normal vestibulo-ocular reflex measurements contrasted with the repeated complaints of dizziness, vertigo and unsteadiness reported by 7 patients (58%). Sodium valproate affected neither vestibulo-ocular responses nor vestibular complaints but was effective in reducing migraine attacks in 8 of the 12 patients. These results demonstrate that the low frequency vestibulo-ocular reflex measurements are normal in patients suffering from migraine without aura. PMID- 8486509 TI - Posttraumatic headache: determining chronicity. AB - In the headache literature, there exists a great deal of discrepancy regarding when posttraumatic headache (PTH) may be classified as chronic. Although chronic pain is usually described as pain persisting for longer than six months, many view chronic posttraumatic headache as persisting for more than two months, including the International Headache Society criteria. Observations made by Brenner and Friedman in 1944 have been repeatedly cited for this determination. Surprisingly, a review of this original source revealed that the term "chronic" was never used when discussing posttraumatic headache over two months duration. The authors, in fact, suggested two months as an "arbitrary" dividing line. Recent studies suggest that many patients with PTH continue to improve or change over the first six months but start to plateau after that time. We feel six months serves as a better time indicator for defining chronicity in cases of posttraumatic headache. This would be more consistent with the current literature concerning chronic pain and the international Headache Society criteria for chronic tension headache. PMID- 8486510 TI - Deficiency in serum ionized magnesium but not total magnesium in patients with migraines. Possible role of ICa2+/IMg2+ ratio. AB - It has been suggested that magnesium (Mg) may play a role in the pathogenesis of headaches. Serum and intracellular measurements of Mg in headache patients have produced inconsistent results. The recent development of an ion-selective electrode for Mg2+ allowed precise measurement of serum ionized magnesium (IMg2+) in patients with various headache syndromes. Low serum IMg2+ and a high ICa2+/IMg2+ ratio were found in 42% of patients having an attack of migraine, but only in 23% of patients with a severe continuous headache. Total serum Mg was normal in both groups of patients. However, in patients with low serum IMg2+ total serum Mg was lower than in patients with normal serum IMg2+. These results are compatible with the serotonin and vascular concepts of migraine pathogenesis. Low IMg2+ and a high ICa2+/IMg2+ would result in cerebral vasospasm and reduced blood flow in the brain. The activity of serotonin receptors can also be affected by changes in IMg2+ levels. The finding of a difference in IMg2+ levels in two different headache types suggests a possible novel classification of headaches and that migraine patients with a low serum IMg2+ or a high ICa2+/IMg2+ ratio may benefit from Mg supplementation. PMID- 8486511 TI - Relation between headaches and neuropsychological functioning among head injury patients. AB - The Luria-Nebraska Neuropsychological Battery (LNNB) and the Minnesota Multiphasic Personality Inventory (MMPI) were administered to 184 head injury patients with varying degrees of headache activity. A multiple regression analysis, controlling for neurological status, compared the 11 LNNB scores of patients with Daily Headaches, Frequent Headaches, Infrequent Headaches, and No Headaches and found that the Arithmetic Scale was the only significant predictor, with the Daily Headache patients performing more poorly than the Infrequent Headache patients. A similar analysis of the 13 MMPI scores indicated that the K, Hs, and Pt Scales were significant predictors. However, post hoc Tukey tests revealed that K and Pt scores did not vary significantly among the four headache groups and only showed that Daily Headaches and Frequent Headaches patients had significantly higher Hs scores than the No headaches group. Subsequent comparisons of patients with and without headaches at the time of testing revealed no differences between the two groups on the LNNB and MMPI, after controlling for age, duration of symptoms, and neurological status. Overall, the results suggested that the relation between headache symptoms and neuropsychological functioning was insignificant. PMID- 8486512 TI - Value of MRI in pediatric migraine. AB - Twenty four pediatric migraineurs were prospectively evaluated to determine if white matter hyperintensities were present on magnetic resonance imaging (MRI). None had white matter findings or brain abnormalities. Five had mucoperiosteal thickening of the paranasal sinuses, which were unrelated to the patients' clinical course. MRI white matter findings are probably not a common occurrence in pediatric migraineurs. In addition, MRI sinus findings are not necessarily related to a child's headache complaints. PMID- 8486513 TI - An association between migrainous aura and hereditary haemorrhagic telangiectasia. AB - Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by a variety of abnormalities of the vasculature. This study investigated by questionnaire an unselected group of 58 patients suffering from HHT to identify and diagnose any headache history. These were compared with a control group comprising 40 patients with an unrelated autosomal dominant disorder, familial adenomatous polyposis. Fifty percent of the HHT patients reported attacks of headache which fulfilled current diagnostic criteria for migraine with aura. This was over four times the figure for the control group and at least 10 times the expected level for a normal population. The auras described by all the affected patients were classic visual disturbances preceding the headaches. Two patients also described typical visual auras unassociated with headache symptoms. The reason for such a clear association between migraine with aura and HHT is uncertain but cerebral arteriovenous malformations seem to be the likely link. A greater understanding of the reasons for the relationship may provide an insight into the pathophysiology of both conditions. PMID- 8486514 TI - Psychophysiological and MMPI personality assessment of headaches: an integrative approach. AB - Multiple psychophysiological measures and personality assessment techniques were combined to facilitate the diagnosis of headache type and improve upon existing methodology. Twenty-four migraine, 24 chronic tension headache patients, and 24 normal age- and gender-matched controls were assessed with bilateral measures of frontalis and occipitalis EMG and blood volume pulse. All subjects completed the MMPI. Results suggest that headache subjects could be differentiated on baseline heart rates and MMPI scales 1,2,3, and 7. Only one physiological measure served as an index of psychological distress, suggesting issues of an interaction between psychophysiological and personality variables, as well as the chronicity of the headache. PMID- 8486516 TI - Orbital phlebography. PMID- 8486515 TI - The effects of streptomycin/lidocaine block on trigeminal neuralgia: a double blind crossover placebo controlled study. AB - This study investigated the long term effect of a peripheral sensory block using streptomycin sulphate on trigeminal neuralgia. A total of twenty subjects, thirteen with idiopathic trigeminal neuralgia (ITN) and seven with traumatic trigeminal neuralgia (TTN) were studied. A double-blind placebo controlled randomized design was used. After the clinical assessment subjects were randomly assigned to receive either 1 g of streptomycin with 3 ml 2% lidocaine, or 3 ml lidocaine alone. The injections were performed adjacent to the branches that served the painful site. These were intraoral injections, more specifically infraorbital and inferior alveolar blocks. Patients received five blocks of either streptomycin/lidocaine or lidocaine alone for a period of five consecutive weeks. On the sixth week they were crossed over. Measures of pain intensity and pain frequency were used to assess treatment outcome. Patients also recorded their side-effects. Repeated measures analysis of variance was used to compare the treatment outcomes between the active and placebo groups. There was no statistically significant differences in the treatment outcomes regarding frequency and intensity of pain attacks. The sensory function of the treated nerves was also not affected. Side effects including facial swelling and pain were a common finding in the patients receiving streptomycin. This study demonstrated no beneficial effects of streptomycin blockade for idiopathic and traumatic trigeminal neuralgia. PMID- 8486517 TI - The link between migraine and dizziness. PMID- 8486518 TI - 38th annual meeting of the Health Physics Society. Atlanta, Georgia, 11-15 July 1993. Abstracts. PMID- 8486519 TI - Inhibitory effects of dopamine on noradrenaline-induced constriction of arterioles in vivo in the striated cremaster muscle. AB - The effect of dopamine on the arterioles (50.8-95.2 microns) in the cremaster muscle was examined to determine its effect on microcirculation. Anesthetized rats were used under a light microscope connected to a videocamera. Drugs were applied using small round filter paper (370 microns in diameter) containing the drug and placed in the immediate vicinity of the arteriole on the cremaster with a micromanipulator. The dose of the drug applied was represented by concentration of the drug solution in which the filter paper was immersed. Dopamine (10(-6)-10( 4)M) induced neither constriction nor dilation of the arteriole in the cremaster. Papaverine (10(-2)M) did not dilate the arteriole. However, the arterioles were constricted by noradrenaline (10(-6)-10(-4)M) and vasopressin (10(-7)M) in a dose dependent manner. Noradrenaline (10(-4)M)-induced constriction was blocked by concomitant application of dopamine (10(-4)M). This effect of dopamine was antagonized by SCH23390 (10(-3)M). However, isoproterenol (10(-3)M) did not affect the arteriole, nor inhibit noradrenaline (10(-4)M)-induced constriction of the arterioles. While forskolin (10(-2)M) alone did not produce constriction or dilation of the arterioles, it inhibited noradrenaline (10(-4)M)-induced constriction of the arteriole. These results suggest that dopamine prevents the constriction of the arteriole induced by noradrenaline, by activation of DA1 receptors, which activates adenylate cyclase. PMID- 8486520 TI - A study on the lung function in alpha 1-antitrypsin-deficient (PiMZ) patients. AB - Laurel and Eriksson published the first report indicating that alpha 1 antitrypsin deficiency predisposed patients to the development of Chronic Obstructive Pulmonary Disease (COPD). For the purpose of early detection, disturbances of pulmonary function in alpha 1-antitrypsin mild deficiency cases (PiMZ) were compared with those of normal cases (PiMM) in caucasian Americans. The marked results are as follows. 1) Parameters of flow-volume curves were more disturbed in PiMZ cases than in PiMM cases. 2) Volumes of isoflow are specially different between PiMZ and PiMM cases. 3) Mechanical properties, like lung work of breathing, were larger in PiMZ cases than in PiMM cases. PMID- 8486521 TI - Nucleotide sequence of the 5' region of the human platelet-derived growth factor A-chain gene. AB - We have isolated and characterized genomic clones of the 5' region of the human PDGF A-chain gene. The putative "TATAA" box was identified 876 bp upstream of the translation initiation site. A significant number of potential regulatory elements were identified in DNA sequences upstream of the "TATAA" box and were also found within the introns sequenced. The DNA sequence results differ significantly from those reported for the PDGF B-chain gene, suggesting a basis for the expression of the PDGF A-chain gene and the B-chain gene under very different conditions. PMID- 8486522 TI - The effect of occupational type of household on mortality in Japan. AB - The mortality of the Japanese population was examined focusing on the effect of household head occupation rather than individual occupations. The 'healthy worker effect' (HWE) which implies lower mortality observed in a working than in a non working populations has been successively observed in comparative studies on mortality in different occupation populations. In this study we report quite similar results analysing the effect of household head occupation. We point out the possibility that HWE should have a component which is shared with the household members if the worker is a household head. We call this component the 'indirect effect'. The results obtained in this study are as follows. The employee household had the lowest mortality followed by self-employed, agriculture and 'others' households. The self-employed household also had a low standardized mortality ratio (SMR) except for diabetes in male. The SMR of the agriculture household was significantly high especially for those above 65 years of age and for suicide in both male and female of age 45 years old and over but low for cirrhosis of liver in male and tuberculosis in both male and female. The SMR of 'Others' household was the highest among the occupational type of households especially between 20-64 years. The similarity in SMR trend among male and female rather than in occupational type of household, despite the fact that males are more likely to be working than females, suggests the presence of indirect effect. Though it is difficult to distinguish direct and the indirect effects completely, we also discuss a method that enables us to distinguish the two effects more effectively. PMID- 8486523 TI - Milk-borne transmission of HTLV-1. PMID- 8486524 TI - Differential expression of a human sperm-specific isozyme in seminoma cells transplanted in Scid-nu(str) mice. AB - An isozyme of human sperm-specific lactate dehydrogenase, LDH-X (C4) (EC 1.1.1.27), which is expressed only in differentiated germ cells (spermatozoa, spermatids and primary spermatocytes after midpachytene), appeared in the xenografted tumor cells of human seminoma and its metastatic lesions (lymph node and kidney) in scid (severe combined immunodeficiency)-nude(streaker) double mutant mice, though it was not expressed in the original tumor of the patient. The morphological pattern of seminoma cells also changed in the xenografts and metastatic lesions as in normal spermatogenesis. Thus, the human seminoma cells showed differential expression of the sperm-specific isozyme in parallel with their morphological changes. However, the sperm-specific isozyme disappeared in the mitotically dividing seminoma cells which were newly established from the LDH X positive xenograft. PMID- 8486525 TI - Possible tumor-initiating and -promoting activity of p-methylcatechol and methylhydroquinone in the pyloric mucosa of rat stomach. AB - The possible tumor-promoting and tumor-initiating activities of p-methylcatechol and methylhydroquinone in the pyloric mucosa of male F344 rats were studied. Ornithine decarboxylase (ODC) and replicative DNA synthesis (RDS) were used as markers of tumor promotion and DNA single strand scission and unscheduled DNA synthesis (UDS) as markers of tumor initiation. The compounds were administered by gastric intubation and results were compared with those after administration of catechol. p-Methylcatechol at doses of 60 to 180 mg/kg body weight dose dependently induced up to 20-fold increase in ODC activity and 9-fold increase in RDS with maxima 24 h after its administration, but it did not induce significant DNA single strand scission or UDS. Methylhydroquinone at a dose of 200 mg/kg body weight induced up to 6-fold increase in ODC activity 24 h, and 5-fold increase in RDS 16 h after its administration, but the induction was not dose-dependent. At a dose of 200 mg/kg body weight it induced DNA single strand scission, but not UDS. These results and previous findings show that the possible tumor-promoting activities of catechol are several times higher than those of p-methylcatechol and 10 times higher than those of methylhydroquinone. PMID- 8486526 TI - Correlation between medium-term multi-organ carcinogenesis bioassay data and long term observation results in rats. AB - The effects of four test chemicals [2-acetylaminofluorene (2-AAF), D,L-ethionine (ethionine), butylated hydroxyanisole (BHA), and catechol] were compared in medium- and long-term in vivo systems. In the medium-term assay, animals were sequentially treated with N-diethylnitrosamine (100 mg/kg body weight, i.p., single injection), N-methylnitrosourea (20 mg/kg body weight, i.p., 4 times during weeks 1 and 2), N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water during weeks 1 and 2), 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times during weeks 3 and 4) and dihydroxy-di-N-propylnitrosamine (0.1% in the drinking water during weeks 3 and 4) for multi-organ initiation, and then treated with one of the four test chemicals for 24 weeks, and killed at week 28 (group 1). In the long-term assay, animals were treated in the same manner and then given basal diet and tap water (group 3) or test chemical continuously (group 4) for the remainder of the lifespan. Animals receiving multi-organ initiation and then maintained on basal diet for 24 weeks (group 2) or their lifespan (group 5) served as controls. Detailed histopathological examinations were performed on all rats. Hepatocellular carcinoma incidences in the long-term assay were found to reflect closely the respective medium-term results. Induction of proliferative forestomach or glandular stomach lesions by BHA and/or catechol, and bladder lesions by 2-AAF and BHA in the medium-term assay also correlated with tumor development in the long-term. Furthermore, inhibition of thyroid proliferative lesions by all test chemicals corresponded with low thyroid tumor incidences in the long-term assay. The observed strong correlation between medium and long-term results confirms the applicability of our medium-term multi-organ carcinogenesis bioassay system for detection of modifying effects of test chemicals in different organs. PMID- 8486527 TI - Cell-density-dependent expression of Cyp1a2 gene in monolayer-cultured adult mouse hepatocytes. AB - Expression of Cyp1a1 and Cyp1a2 genes was investigated in adult C57BL/6NCrj mouse hepatocytes for up to 5 days after transfer to monolayer culture. CYP1A1 mRNA was substantially induced by treatment with 3-methylcholanthrene during the observation period, independently of the seeded cell density. However, expression of CYP1A2 mRNA was dependent on cell density and was higher in cells cultivated at lower density. With increasing culture period the expression was decreased, so that only negligible levels were evident by day 5, and reduced expression of constitutive and induced CYP-1A2 mRNA became apparent earlier in more densely seeded cells. This was not related to differences in numbers of inducer molecules per cell. While mouse hepatocytes incorporated tritium-labeled thymidine under the given culture conditions, induction of expression of the two Cyp1a genes did not show any direct relationship with DNA synthesizing activity. These observations suggest some role for Cyp1a2 during changes in physiological state. PMID- 8486528 TI - Activation of Cyp1a1 and Cyp1a2 genes in adult mouse hepatocytes in primary culture. AB - Expression of Cyp1a1 and Cyp1a2 genes was investigated in adult C57BL/6NCrj mouse hepatocytes in primary culture for up to 5 days. When the cells were cultivated as monolayers on collagen-coated dishes, CYP1A1 mRNA species were prominently induced after treatment with 3-methylcholanthrene (MCA) throughout the observation period. Substantial induction of CYP1A2 mRNA by MCA was also observed at day 1 of cultivation, followed by a decrease to very low levels thereafter. In contrast, when cultivated on non-coated dishes, the hepatocytes formed multicellular aggregates (spheroids) and prominent induction of both mRNA species was found for up to 5 days. Constitutive expression of CYP1A2 mRNA in spheroid culture was maintained throughout the observation period, whereas that in monolayer culture decreased rapidly. The time-course of the induced CYP1A2 mRNA amounts after the treatment with MCA or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) followed the same pattern as that of CYP1A1 mRNA. Expressed amounts of CYP1A1 or CYP1A2 mRNA in spheroid culture were higher than or similar to the levels in the case of in vivo production, respectively. Induction of both mRNA species was also observed in hepatocytes from nonresponsive DBA/2NCrj mouse in spheroid culture, but the expressed amount after MCA treatment was far smaller than for C57BL/6NCrj cells, despite equivalent expression in the two strains after TCDD. Activities of aryl hydrocarbon hydroxylase (AHH) and acetanilide 4 hydroxylase (AAH) were elevated with either type of cultivation after treatment with MCA or TCDD. Ratios of AAH to AHH were not changed between the two cultures after 24 h treatment. However, the ratios in spheroid culture after 48 h treatment increased, whereas they did not change in monolayer culture. The present observations indicate that the spheroid culture is more suitable than the monolayer system for studying the mechanism of Cyp1a2 gene expression in adult mouse hepatocytes. PMID- 8486529 TI - Use of serum gamma-enolase and aldolase A in combination as markers for renal cell carcinoma. AB - To clarify whether measurement of serum gamma-enolase and aldolase A in combination is useful for diagnosis and prediction of prognosis in cases of renal cell carcinoma (RCC), levels of both markers were evaluated by enzyme immunoassay in 132 patients with RCC. Serum gamma-enolase was elevated in 53 of the cases (40%) whereas serum aldolase A was elevated in 45 (34%). At least one of the two markers was elevated in 54% of the patients (71/132), this value being significantly higher than the positive rates for either gamma-enolase (40%) or aldolase A (34%) evaluated singly. Expression of the two markers assessed in combination became more positive with stage progression, values being 37% in stage I, 59% in stage II, 72% in stage III, and 74% in stage IV. In contrast, patients with benign urological diseases demonstrated positive rates for gamma enolase and aldolase A as low as 3% and 6%, respectively. Increase in serum gamma enolase was correlated with stage, tumor size, and histological grade, whereas elevated levels of serum aldolase A were associated only with advancing stage. In 15 patients with recurrent diseases, 11 (73%) had elevated levels of gamma enolase and 5 (33%) had elevated levels of aldolase A, indicating that gamma enolase is the more sensitive of the two for detection of recurrence. Patients with elevated levels of both gamma-enolase and aldolase A had less favorable survival than those expressing no or only one of the markers, indicating that simultaneous measurement of the two markers provides information directly relevant to prognosis in cases of RCC. PMID- 8486530 TI - Morphometric analysis of colonic adenomatous polyps. AB - Morphometric evaluation of adenomas of the colon to determine their degree of dysplasia is still controversial, since subjective factors influence the decision concerning benignancy or malignancy. Some indices have been proposed to assist in categorizing intermediate lesions into benign or malignant. However, these indices show a wide range of distribution. To evaluate the reliability of one such index, the index of structural atypism (ISA, area of glands/area of stroma), we studied polyps as a whole, and found great variability of index values within a single polyp. PMID- 8486531 TI - Antimetastatic effect by anti-adhesion therapy with cell-adhesive peptide of fibronectin in combination with anticancer drugs. AB - We have investigated the therapeutic effect of CH-271 fusion polypeptide containing both cell-binding domain (C-274) and heparin-binding domain (H-271) of fibronectin in combination with anticancer drugs such as doxorubicin (DOX) or mitomycin C (MMC) on tumor metastasis of different types of tumors. CH-271 fusion polypeptide alone significantly inhibited both liver and lung metastasis when it was co-injected with L5178Y-ML25 T-lymphoma, RAW117-H10 B-lymphoma or B16-BL6 melanoma cells, and spontaneous lung metastasis of B16-BL6 melanoma cells when administered i.v. seven times before or after surgical excision of the primary tumors. Combined treatments with CH-271 and either DOX or MMC significantly inhibited liver and lung metastasis of lymphoma or melanoma cells respectively, as compared with either treatment alone or the untreated control. Administrations of CH-271 and DOX in combination substantially prolonged the survival time of mice injected i.v. with L5178Y-ML25 cells. CH-271 or DOX was effective for inhibiting the invasion of L5178Y-ML25 cells into Matrigel in a concentration dependent manner. Our previous study has shown that CH-271-mediated inhibition of tumor invasion may be due in part to the anti-cell adhesive property without affecting the cell growth, whereas the anti-invasive effect of DOX was established to have resulted from the growth inhibition of tumor cells. Moreover, the combination of CH-271 with DOX provided a more effective inhibition of tumor invasion into Matrigel than did either alone. Thus, we have demonstrated that the combination of anti-cell adhesive CH-271 and anticancer drugs such as DOX or MMC, i.e. anti-adhesion therapy and chemotherapy, is a new approach that offers enhanced (additive) inhibitory effects on tumor metastasis and invasion. PMID- 8486532 TI - Hyperthermic enhancement of cytotoxicity and increased uptake of cis diamminedichloroplatinum(II) in cultured human esophageal cancer cells. AB - Thermal enhancement of cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP) has been well recognized and applied clinically to chemotherapy of various malignancies, but its fundamental mechanism remains to be elucidated. In order to obtain a clue to this mechanism, we analyzed the effect of hyperthermia on the uptake and subsequent distribution of [195mPt]CDDP in two lines of esophageal cancer cells (KYSE-150 and KYSE-170) established from clinical patients. First, we observed a significant increase in [195mPt]CDDP uptake by both types of cells at increasingly higher temperatures. The incorporated CDDP was distributed between the nucleus and the cytosol at a ratio of approximately 3:1, and the ratio remained the same at various temperatures. The CDDP was found in all four molecular fractions, i.e., DNA, RNA, protein, and TCA-soluble, with a slight preference for DNA at higher temperatures. Enhancement of cytotoxicity required simultaneous, and not sequential, treatments with CDDP and hyperthermia; hyperthermia after CDDP treatment increased the efflux of CDDP from the cells, and rather reduced the cytotoxicity of CDDP. These results suggest that thermal enhancement of the cytotoxicity of CDDP is caused mainly by acceleration of the drug entry into the cell, probably due to increased permeability, and a consequent increase in the amount of CDDP binding to DNA. This mechanism gives support for clinical trial of simultaneous treatment with CDDP and hyperthermia. PMID- 8486533 TI - Cytokines induce uridine phosphorylase in mouse colon 26 carcinoma cells and make the cells more susceptible to 5'-deoxy-5-fluorouridine. AB - The antiproliferative activity of 5-fluorouracil (5-FUra) and 5'-deoxy-5 fluorouridine (5'-dFUrd), used in combination with typical cytokines and growth factors, was investigated in mouse colon 26 carcinoma cells. Tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interferon gamma (IFN gamma) at low doses showing < 50% inhibition of cell growth by themselves enhanced the susceptibility of the cells to the activity of 5'-dFUrd. In particular, a mixture of these cytokines greatly enhanced the activity of 5' dFUrd and 5-FUra by up to 12.4- and 2.7-fold, respectively, whereas the activity of other cytostatics was only slightly changed (< 1.5-fold). Basic fibroblast growth factor also increased the susceptibility, but only to 5'-dFUrd. This preferential enhancement of the activity of 5'-dFUrd would be due to induction by the cytokines of uridine phosphorylase (Urd Pase), by which 5'-dFUrd is converted to 5-FUra. TNF alpha, IL-1 alpha, IFN gamma, and a mixture of these factors increased the enzyme activity by up to 3.7-fold in colon 26 cells. Consequently, the anabolism of 5'-dFUrd to fluoronucleotides and the incorporation of 5-FUra into RNA in colon 26 cells were increased by TNF alpha treatment. In addition, the increase by the cytokine mixture in the susceptibility to 5'-dFUrd was abolished by an inhibitor of Urd Pase, 2,2'-anhydro-5-ethyluridine. These results indicate that induction of Urd Pase activity by cytokines is a critical event that increases the susceptibility to 5'-dFUrd. PMID- 8486534 TI - Caffeine modulates the antitumor activity and toxic side effects of adriamycin. AB - To improve both the survival and the response rate of patients, it is necessary to find modifiers which enhance the effects of known anticancer agents. In this study, we examined the effects of caffeine on the antitumor activity and side effects of antitumor agents, using CDF1 male mice. The combination of caffeine with adriamycin significantly enhanced the antitumor activity of adriamycin, by 1.5-fold and 1.9-fold in single- and multi-administration schedules, respectively, compared to the activity of adriamycin only. However, the combination of caffeine with cisplatin had no effect on the antitumor activity of cisplatin in either administration schedule. We examined two biochemical parameters, lipid peroxide level and glutathione peroxidase activity, as indices of adriamycin-induced side effects. The caffeine combination did not enhance the adriamycin-induced changes in these two parameters. Regarding the lethal effect of adriamycin, the caffeine combination had no effect in the single administration schedule, but in the multi-administration schedule, it tended to reduce this acute toxicity. These results suggest that the combination of caffeine with adriamycin can significantly increase the in vivo antitumor activity of this agent without increasing its side effects. PMID- 8486535 TI - On not knowing beforehand. AB - This paper starts from recommendations of Freud and Jung on the desirable attitudes of analysts to their patients, and especially open-mindedness which I have named 'not knowing beforehand'. I use the metaphor of a filing cabinet to illustrate how to empty one's mind and, so to speak, lock up one's knowledge, memory, and desires in that filing cabinet. That gives space for the patient to structure his interview. I illustrate how knowing beforehand can disrupt an interview and how 'filing-cabinet material' will get used when tailored to the interview structure. The metaphor is used for the sake of simplicity. It does not include the complexity of the analytical dialectic. PMID- 8486536 TI - 'In a dark time, the eye begins to see'. AB - In this paper I discuss a patient whose shadow became his rival, or as Jung put it, 'The shadow is lived'. I describe the beginning of a process of the assimilation of shadow contents, whereby the rupture between ego and shadow can no longer be maintained. I also discuss how it is primarily through the mutual experience and analysis of archetypal images that the unconscious contents become more integrated. In my clinical illustrations I also explore the relationship between my patient's fight with his shadow and his experiences of childhood shame. I consider how fear expressed through a panic attack may open a royal door to the unconscious, and the way in which its mediation through empathy and analysis can lead to unconscious infantile contents becoming more accessible. In addition, I show how, once some of the fear had subsided, it became possible for play to enter into the analysis. PMID- 8486537 TI - Electra: the dark side of the moon. PMID- 8486538 TI - When the meaning gets lost in the body: psychosomatic disturbances as a failure of the transcendent function. PMID- 8486539 TI - The microbiology of bottled natural mineral waters. PMID- 8486540 TI - Isolation and attempted introduction of sugar alcohol-utilizing bacteria in the sheep rumen. AB - Bacteria that use sorbitol, xylitol, maltitol and dulcitol (galactitol) were isolated from the sheep rumen following enrichments in which bacteria were grown in rumen fluid medium where the sugar alcohol was the only added energy source. Only isolates obtained with sorbitol and maltitol grew sufficiently rapidly to be considered for enrichment by the sugar alcohol in vivo. Isolate SS2, a strain of Selenomonas ruminantium var. lactilytica which grew on sorbitol at 0.87 h-1, was selected for further study and a rifampicin-resistant mutant, SS2/R5, was isolated to facilitate tracking in the mixed population. Despite an initial transient increase in numbers, a significant population of S. ruminantium SS2/R5 failed to establish in sheep which were dosed twice daily with 10 g of sorbitol. Continuous infusion of sorbitol increased numbers only slightly compared with twice-daily dosing. In vitro experiments indicated that strain SS2/R5 grew less well in the presence of other rumen organisms, particularly ciliate protozoa, than in pure culture. Furthermore, the concentration of sorbitol in vivo was lower than predicted from in vitro experiments, indicating that sorbitol was absorbed rapidly from the rumen. Similar observations were made with xylitol, dulcitol and maltitol. Proposed enrichment strategies that use sugar alcohols or other materials to support the growth of introduced bacteria will thus have to take account of the combined problems of microbe-microbe interactions and the loss of the compounds by absorption from the rumen. PMID- 8486541 TI - Culture media for the differentiation of isolates of Yersinia ruckeri, based on detection of a virulence factor. AB - Strains of the bacterial fish pathogen Yersinia ruckeri were identified with the API 20E system and distinguished on the basis of whole cell agglutination with antisera, sorbitol fermentation and polymyxin B sensitivity. Strains which were shown to possess the virulence-associated heat-sensitive factor (HSF) were shown to grow preferentially on culture media containing sodium dodecyl sulphate (SDS) and to produce a creamy deposit around the colonies. By contrast, strains lacking this factor (HSF-) grew poorly and without forming a deposit. Enhancement of the differentiation between the two types was shown by the incorporation of Coomassie brilliant blue dye into agar containing 1% SDS, and the uptake of Coomassie blue and Congo red was shown to be temperature-dependent. Most strains tested were shown to belong to serotype I, and were sensitive to polymyxin and did not ferment sorbitol. With the medium developed most serotype I strains but not those of other serotypes were shown to possess HSF. It is suggested that the medium is used in epidemiological studies of Y. ruckeri. PMID- 8486542 TI - Mesenterocin 52, a bacteriocin produced by Leuconostoc mesenteroides ssp. mesenteroides FR 52. AB - One hundred and sixty-five isolates of Leuconostoc spp. were tested for bacteriocin production. Only one strain, Leuc. mesenteroides ssp. mesenteroides FR 52, isolated from a raw milk, produced a bacteriocin which was named Mesenterocin 52. This bacteriocin inhibited other Leuconostoc strains and several strains of Enterococcus and Listeria spp. No activity was found against lactococci and lactobacilli. The antibacterial spectrum differed from that of previously described Leuconostoc bacteriocins. Mesenterocin 52 was secreted into the medium during the growth phase. It was inactivated with protease treatments. At pH 7.0 it had a relative stability after heating at 100 degrees C (15 min), but it had a greater stability at pH 4.5 than at pH 7.0 after 6 h at 80 degrees C. The apparent molecular mass was estimated to be less than 10 kDa by ultrafiltration. Mesenterocin 52 showed a bactericidal effect on Leuconostoc paramesenteroides DSM 20288. PMID- 8486543 TI - Enterocin 226NWC, a bacteriocin produced by Enterococcus faecalis 226, active against Listeria monocytogenes. AB - Enterococcus faecalis 226, isolated from natural whey cultures utilized as starters in the manufacture of mozzarella cheese from water-buffalo milk, produces a bacteriocin designated enterocin 226NWC. The bacteriocin was isolated from culture supernatant fluids of the producer strain and was active against strains of the same species and Listeria monocytogenes, but not against useful lactic acid bacteria. Enterocin 226NWC is a protein with an apparent molecular weight of about 5800; it is relatively heat-stable and has a bactericidal mode of action. Listeria monocytogenes, growing in the presence of the enterocin 226NWC producer strain in broth and in reconstituted skim milk, was inhibited. PMID- 8486544 TI - A laboratory apparatus for the generation and biocide efficacy testing of Legionella biofilms. AB - The construction and operation of a laboratory biofilm generator designed to grow sessile populations of legionellas for biocide efficacy testing is described. Some examples of static biocide testing on both sessile and planktonic populations of Legionella bozemanii are discussed along with other potential applications of the apparatus. PMID- 8486545 TI - A sandwich enzyme-linked immunosorbent assay (ELISA) for detection of Pseudomonas fluorescens and related psychrotrophic bacteria in refrigerated milk. AB - A sandwich ELISA (enzyme-linked immunosorbent assay) was developed for detection of Pseudomonas fluorescens and related psychrotrophic bacteria in refrigerated milk. Polyclonal antibodies were raised in rabbits against protein F from the cell envelope of Pseudomonas fluorescens AH-70. The anti-protein F antibodies (anti-PF) bound to the wells of a microtitre plate were used to capture this protein from the micro-organisms on milk samples. Further immunorecognition of the captured antigen was attained with the same anti-PF antibodies conjugated to biotin. ExtrAvidin-peroxidase was used to detect the biotinylated antibodies bound to their specific antigens. Subsequent enzymic conversion of substrate gave clear absorbance differences when assaying milk samples containing Ps. fluorescens strains of different origin as well as related psychrotropic micro organisms. PMID- 8486546 TI - Enumeration of Escherichia coli in cooked and raw meats by ion mobility spectrometry. AB - A novel method for enumerating Escherichia coli in foods is described. It is based on the production of o-nitrophenol (ONP) from o-nitrophenyl-beta-D glucuronide as detected by an ion mobility spectrometer. The time taken for the detection of ONP in a food sample was inversely proportional to the logarithm of the initial E. coli population. Escherichia coli could be detected at a level of 10 g-1 within 9 h. PMID- 8486547 TI - Characterization of bacteriocin produced by Pediococcus pentosaceus from wine. AB - Twenty strains of Pediococcus pentosaceus isolated from wine were examined for production of bacteriocins. Only two of them showed inhibitory activity, Ped. pentosaceus N4p against the indicator strains of the same species and N5p against 19 strains of the three genera of lactic acid bacteria from wine. The antimicrobial substance from N5p strains was removed by membrane (0.2 micron) filtration, destroyed by organic solvents and proteolytic enzymes. It was stable for 60 min at 100 degrees C. The bacteriocin was produced early in the growth cycle and its production was maximum after 48 h of culture in tomato juice medium at an initial pH of 6.5. The bactericidal effect was observed. PMID- 8486548 TI - Fibronectin and proteolytic fragments of fibronectin interfere with the adhesion of Staphylococcus epidermidis to plastic. AB - The adhesion of five strains of slime-positive Staphylococcus epidermidis to plastic microwells was significantly diminished (P < 0.005) in a concentration dependent fashion when wells were previously coated with increasing concentrations (1.6-13.1 micrograms cm-2) of human fibronectin (FN). The adhesion of four of five strains was significantly reduced when wells were coated with 3.2 micrograms cm-2 of FN and at concentrations > or = 6.5 micrograms cm-2 the adhesion of all slime-positive strains was significantly reduced. The coating of microwells with chymotryptic fragments of FN containing the heparin-binding, gelatin-binding, or cell-binding domains also reduced bacterial adhesion but none of the fragments exceeded the anti-adhesive activity of intact FN. A comparison of FN-coated or albumin-coated microwells showed that both proteins caused a significant reduction in the adhesion of test strains to plastic but that the anti-adhesive activity of FN was greater than albumin at all concentrations tested. The adhesion of the slime-negative phase variant of one of the test strains to plastic was neither enhanced nor reduced by FN coating indicating that the production of an exopolysaccharide by Staph. epidermidis influences interactions with protein-coated surfaces. These results support the contention that FN does not mediate the adhesion of all strains of Staph. epidermidis to plastic surfaces. PMID- 8486549 TI - Comparison of Signal and Bactec NR-660 blood culture systems. AB - The Signal blood culture system was compared with the Bactec NR-660. A total of 1617 blood culture sets yielded 143 (8.8%) significant isolates; 113 (79.0%) were from positive bottles in both the Bactec and Signal systems. Twelve organisms (8.4%) were detected and isolated from the Signal system only and another 18 (12.6%) from the Bactec system only. Of these 18, five were Signal-positive but the organism was not recovered and four organisms were isolated from negative Signal bottles on terminal subculture. The time taken to detection for each system was similar; the Signal system detected 68% and the Bactec 63% of significant positives within 24 h. At 48 h Bactec detected 91% and the Signal 85%. A significantly-reduced number of bottles which gave a positive signal but were negative by microscopical and cultural methods was found, compared with previous reports. The 1 h incubation period prior to the insertion of the Signal growth indicator device was considered to be the cause of this reduction in the proportion of false positives. Fifty-five percent (42/77) of the Bactec false positives were due to delta growth value. This is when there is an increase in the growth index of > or = 15 without the positive threshold level of 30 being attained. This occurred in the anaerobic bottle on day 2 with 42 bottles. Another 40% (31/77) of the false positives had a growth value between the positive threshold of 30 and a value of 35. Eighty (4.9%) of Bactec and 65 (4.0%) of Signal sets yielded clinically non-significant isolates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486551 TI - Heat resistance of Listeria monocytogenes by two recovery media used with and without cold preincubation. AB - Three strains of Listeria monocytogenes were heat-treated at three temperatures in physiological saline by a capillary tube method. Recovery of heat-treated bacteria was performed on blood agar and on tryptose phosphate agar with ferric citrate and aesculin (TPA-FE). Both media were used in two ways: (1) incubation at 37 degrees C for 7 d, and (2) preincubation at 4 degrees C for 5 d in order to obtain repair of heat-injured bacteria, followed by incubation at 37 degrees C for 7 d. D and z values were determined. In both incubation procedures, better average recovery was obtained on blood agar than on TPA-FE. Thus, higher D values were recorded when blood agar was used. In most cases the differences were statistically significant. Repair at 4 degrees C of heat-injured bacteria occurred on both media but the proportions of repaired bacteria were higher on blood agar. The repair on this medium was generally reflected in higher D values for preincubated samples. Some significant differences in heat resistance were noted between the strains. PMID- 8486550 TI - Viable but non-culturable salmonellas in soil. AB - An enzyme-linked immunosorbent assay (ELISA) and a microwell fluorescent antibody (FA) direct count method have been developed for the monitoring of salmonellas in soil. Both methods have a minimum detection level of ca 10(6) cells per gram of soil. The FA direct count method gave a linear recovery for the inoculum range 10(6)-10(9) cells per gram of soil. When monitored by plate counts the survival of salmonellas was greater in a sterile than in a non-sterile soil. Evidence was found for the production of viable but non-culturable salmonellas in non-sterile soil; plate counts dropped rapidly with time, but FA direct counts and ELISA remained level. The salmonella cells became progressively smaller and rounder with time. Dead salmonella cells introduced into soil rapidly disappeared. PMID- 8486552 TI - Production and specificity of poly- and monoclonal antibodies raised against Shewanella putrefaciens. AB - Polyclonal antibodies were raised in rabbits and mice against Shewanella putrefaciens. Murine monoclonal antibodies were produced against the type strain (ATCC 8071) as well as wild type strains isolated from fish products. The specificities of four polyclonal and 12 monoclonal antibodies were tested by dot blotting, an indirect and a competitive ELISA against 16 Gram-negative strains; including six strains of S. putrefaciens and one strain of Pseudomonas rubescens (NC 10695). All polyclonal antibodies reacted strongly with S. putrefaciens and with Ps. rubescens and cross-reacted with the nine other bacteria (Pseudomonas spp., Aeromonas spp. and Vibrio anguillarum). The monoclonal antibodies could be divided into three groups with different patterns of specificity. The largest group (8 monoclonal antibodies) reacted strongly with S. putrefaciens and with Ps. rubescens and showed only weak reactions with the other strains. The results confirm that Ps. rubescens should be classified as S. putrefaciens. PMID- 8486553 TI - Isolation and characterization of a Bacillus strain capable of degrading the extracellular glucan from Cellulomonas flavigena strain KU. AB - Bacteria capable of utilizing the water-insoluble purified extracellular (1-->3) beta-D-glucan (curdlan) from Cellulomonas flavigena strain KU by extracellular enzymes, were isolated and characterized. Enrichment cultures from a Winogradsky column were incubated anaerobically at 55 degrees C with curdlan as the sole source of carbon. Colonies surrounded by zones of clearing were selected from subcultures on solid curdlan media. One of the isolates was chosen for further study and identified by conventional methods, API-tests with calculation of similarity coefficients and ID-scores, estimation of mol% (G+C) and DNA-DNA liquid hybridization. The isolate is a facultatively anaerobic, facultatively thermophilic Bacillus sp. Identification at the species-level was not achieved. The isolate was characterized by some rare traits among bacilli, but it remains unresolved whether it defines a new taxon. PMID- 8486554 TI - Purification and properties of the endocellular beta-glucosidase of Candida cacaoi Buckley and Van Uden CBS 2020. AB - The endocellular enzyme beta-glucosidase of Candida cacaoi was purified by ion exchange chromatography and gel filtration. The molecular weight was 220 +/- 10 kDa; its optimum pH was between 4 and 5.5 and its optimum temperature was 60 degrees C. This enzyme was active against soluble glucosides tested with beta(1 2), beta(1-3), beta(1-4) and even alpha(1-4) and alpha(1-6) and was inhibited by D-glucono-delta-lactone. The enzyme was constitutive but its synthesis was repressed by glucose. PMID- 8486555 TI - Bactericidal activity of disinfectants on Listeria. AB - The bactericidal activity on Listeria spp. of nine disinfectants used in the food industry was studied by previously published methods. The disinfectants were diluted to the test concentration in sterile standard hard water. Various types of chemical agents were evaluated, including phenolic compounds, alcohols, quaternary ammonium compounds, surface-active agents, aldehydes and disochlorine tablets. The following strains isolated from cheese were studied: Listeria innocua, L. welshimeri, L. monocytogenes 1/2a, 1/2b, 1/2c and 4b. The results show that the listerias are not particularly resistant to disinfectants but the efficacy of some agents is affected by organic matter. PMID- 8486556 TI - A simple, rapid and sensitive presence/absence detection test for bacteriophage in drinking water. AB - A rapid, simple and sensitive direct bacteriophage presence detection method for 500 ml drinking water samples has been developed. The method includes a glass device consisting of a jar containing the water sample and an immersible probe filled with solidified soft agar containing bacterial host cells. Host bacteria in logarithmic phase were added to the experimental volume and the probe was submerged. The entire device was incubated in a water bath at 36 degrees C. Plaques of somatic bacteriophage infecting Escherichia coli strain CN13, could be detected within 3 h. Male-specific bacteriophages infecting E. coli F+ amp were detected within 6 h. Bacteriophage infecting the anaerobe Bacteroides fragilis subsp. fragilis HSP40 were detected after 8 h. Application of this device and the associated technique, enabled a one-step detection of 1 pfu of E. coli or Bact. fragilis specific bacteriophage in 500 ml drinking water samples. PMID- 8486557 TI - External quality assessment in water microbiology: statistical analysis of performance. AB - A UK-based scheme of water microbiology assessment requires participants to record counts of relevant organisms. Not every sample will contain the target number of organisms because of natural variation and therefore a range of results is acceptable. Results which are tail-end (i.e. at the extreme low or high end of this range) could occasionally be reported by any individual laboratory by chance. Several tail-end results might imply a laboratory problem. Statistical assessment is done in two stages. A non-parametric test of the distribution of tail-end counts amongst laboratories is performed (Cochran's Q) and, if they are not random, then observed and expected frequencies of tail-end counts are compared to identify participants who may have reported excessive numbers of low or high results. Analyses so far have shown that laboratories find high counts no more frequently than would be expected by chance, but that significant clusters of low counts can be detected among participants. These findings have been observed both in short-term and in long-term assessments, thus allowing detection of new episodes of poor performance and intermittent problems. The analysis relies on an objective definition of tail-end results. Working definitions are presented which should identify poor performance in terms of microbiological significance, and which allow fair comparison between membrane-filtration and multiple-tube techniques. Smaller differences between laboratories, which may be statistically significant, will not be detected. Different definitions of poor performance could be incorporated into future assessments. PMID- 8486558 TI - Acetic, lactic and citric acids and pH inhibition of Listeria monocytogenes Scott A and the effect on intracellular pH. AB - The effects of acetic, lactic and citric acids and pH on the growth and intracellular pH (pHin) of Listeria monocytogenes Scott A were documented and compared for total acid concentrations ranging from 50 mmol ml-1 to 250 mmol ml-1 for acetic and lactic acids and from 25 mmol ml-1 to 100 mmol ml-1 for citric acid. Initial pH values ranged from 4.7 to 6.0. Although the growth rate of L. monocytogenes Scott A was slower when incubated at 25 degrees C than at 37 degrees C, the relative acid and pH inhibition was identical at both temperatures. As the initial pH values decreased and/or the total acid concentrations increased, the growth rates of L. monocytogenes Scott A decreased. Compared at equal initial pH values and on an equimolar total acid basis, the relative inhibition effect was generally acetic > lactic > citric. When based on initial undissociated acid concentrations, the inhibition effect was citric > lactic > acetic. The effect of differing acid and pH environments on pHin was determined. At equimolar total acid concentrations, the pHin of the cell was changed the least by citric acid and the most by acetic acid. Growth rates were influenced by the pHin and the acid used to adjust the system. PMID- 8486559 TI - Factors affecting spoilage microflora succession on lamb carcasses at refrigeration temperatures. AB - Three bacterial groups were detected during the shelf-life of lamb carcasses stored at refrigeration temperatures: coryneforms (mostly Brochothrix thermosphacta), Gram-positive cocci (staphylococci) and Gram-negative bacilli (Pseudomonas spp. and Moraxella spp.). Influence of categorical variables such as sampling day, sampling area and sampling method on their recovery was analysed by a chi-square test of independence and loglinear analysis. Hierarchical loglinear modelling proved to be very useful as several three-way interactions of factors were observed. PMID- 8486560 TI - Transfer of hybrid plasmids based on the replicon pRRI7 from Escherichia coli to Bacteroides and Prevotella strains. AB - New shuttle vectors based on a Prevotella ruminicola 9.5 kb cryptic plasmid (pRRI7) inserted within the Escherichia coli vector pKC71, carrying the Ccr/Emr Bacteroides marker, were constructed. These constructs (pKBR23-1 and pKBR23-2) were transferred into Bacteriodes distasonis, Bacteroides thetaiotaomicron, Bacteroides uniformis and into P. ruminicola NCFB 2202 either by conjugal mobilization or by electroporation. Another pRRI7 derivative based on pKC72, pKBR23-3, was smaller (13.1 kb) and non-mobilizable. By electroporation, it was transferred to Bact. distasonis and P. ruminicola. Being derived from pRRI7 which is compatible with the shuttle plasmid pRRI207, the host/vector combination involving P. ruminicola NCFB 2202 and pKBR23-3 offers new possibilities for genetic investigations in rumen anaerobic bacteria after further introduction of a second readily selectable marker within pRRI207 or pKBR23-3. PMID- 8486561 TI - Intestinal colonization of young chicks with Escherichia coli O157:H7 and other verotoxin-producing serotypes. AB - The susceptibility of chicks to colonization with Escherichia coli O157:H7 and other verotoxin-producing serotypes was studied. The E. coli colonized the caeca of both broilers and layers after oral administration of the challenge. The extent of colonization was dependent on challenge dose, age of chicks at the time of challenge, breed of chicks and length of time after exposure. A rapid increase in caecal colonization and a decrease in crop colonization was evident during the first few hours after challenge, with a maximum in the caeca at 6 h. Escherichia coli persisted in caecal contents as well as on caecal walls throughout the course of the experiments (14 d), but at much lower levels compared with the 6 h post-challenge. PMID- 8486562 TI - Production of hyperimmune bovine colostrum against Campylobacter jejuni. AB - Serial immunization of dairy cows with Campylobacter jejuni resulted in an enhanced serum antibody response and production of hyperimmune colostrum in all vaccinated animals. An approximate 10-fold decrease in the Camp. jejuni-specific antibody titres in colostrum was observed within 2 d post-partum. The lyophilized colostral concentrate fed to newborn calves resulted in a rapid increase in serum antibody response. Specific Camp. jejuni immunoglobulins could be detected in these animals for a further 10 weeks. The lyophilized hyperimmunized colostrum was very stable in vitro at different storage temperatures. It could be used for passive immunization to campylobacteriosis. PMID- 8486563 TI - Resistance to the antimicrobial agents of bacteria isolated from non-sterile pharmaceuticals. AB - The in vitro antimicrobial resistance of 391 bacterial strains isolated from 389 samples of oral and topical medicaments was examined. The numbers of strains isolated (and percentage of samples that present them) were: 234 Bacillus (32.1%), 79 Staphylococcus (13.6%), 46 Micrococcus (11.3%), nine Pseudomonas (1.5%), eight Acinetobacter (1.5%), five Enterococcus (1.2%), three Alcaligenes (0.8%), two Escherichia and Enterobacter (0.5%), one each Providencia, Serratia and Streptococcus (0.2%). Gram-positive bacteria were isolated from topical and oral medicaments and Gram-negative rods were detected only in topical medicaments. The 97.4% of Bacillus strains were resistant to lincomycin and B. cereus was resistant to beta-lactam and trimethoprim-sulphamethoxazole. Staphylococcus spp. showed a high percentage of resistant strains to ampicillin (51.8%), tetracycline (40.5%) and trimethoprim-sulphamethoxazole (48.1%). Staphylococcus epidermidis had the highest number of multiresistant strains. The 23.9% of Micrococcus strains were resistant to colistin. Enterococcus and Streptococcus strains showed multiresistance to penicillin G, aminoglycosides and erythromycin. The 61.5% of Gram-negative rod strains showed multiresistance to beta-lactam antibiotics and erythromycin; Pseudomonas spp. were the most resistant. PMID- 8486564 TI - The application of laser diffractometry to study the water content of spores of Bacillus sphaericus with different heat resistances. AB - The distribution of water in the protoplast and integument of three populations of Bacillus sphaericus spores was determined by laser diffractometry together with the sizes of their integuments and protoplasts. The spores were produced at 15, 20 and 30 degrees C. Spores grown at 15 degrees C had protoplast and integument water contents similar to those produced at 20 degrees C, while those grown at 30 degrees C had significantly lower water contents than the other two populations. The inner (or protoplast) radii of the spores produced at 15, 20 and 30 degrees C were 0.41 +/- 0.02 microns, 0.42 +/- 0.01 microns and 0.38 +/- 0.02 microns whilst the outer (or whole spore) radii were 0.56 +/- 0.01 microns, 0.58 +/- 0.01 microns and 0.52 +/- 0.02 microns respectively. The ratios of integument to protoplast radius were 0.40 +/- 0.02, 0.43 +/- 0.07 and 0.41 +/- 0.03 respectively. PMID- 8486565 TI - Growth and physiological characteristics of Bacillus subtilis L-forms. AB - The specific growth rate of stable Bacillus subtilis L-forms was slower (mu = 0.127) than the cell-walled form (mu = 0.219) when measured by optical density (O.D.). However, the L-form growth rate increased (mu = 0.288) when determined by viable cell counts. L-forms of B. subtilis appear to enter a phase of rapid cell division, followed by a period of cell enlargement which is associated with an increase in the number of cells with vacuoles and granules. Thus, maximum viable L-form numbers and DNA content were attained at approx. 30h, before maximum protein content was achieved (46h) and before maximum O.D. was observed at 71 h. Measurements showed that L-form cell size increased even after cell division had stopped. O.D. was therefore inaccurate for assessment of L-form growth. L-forms were sensitive to osmotic shock and unlike the cell-walled organisms from which they were derived, were resistant to penicillin, indicating a loss of peptidoglycan. The L-forms were similar to cell-walled forms in that antibiotic(s) and proteases were produced. PMID- 8486566 TI - Studies on the ecology of aquatic bacteria of the lower Niger Delta: multiple antibiotic resistance among the standard plate count organisms. AB - The ecology of multiple antibiotic resistant (MAR) bacteria in the fresh-waters of the lower Niger Delta was studied in the Port Harcourt area, Rivers State. On the basis of decreasing pollution levels three zones, A, B, C, were recognized. Cell recovery by two viable count media, casein-peptone-starch (CPS) and plate count (PC) agar containing chloramphenicol, tetracycline, penicillin, streptomycin or ampicillin were compared in an initial study. Higher numbers of antibiotic resistant (AR) bacteria were recovered on CPS containing tetracycline, penicillin, streptomycin and ampicillin from the faecally-polluted New Calabar River (zone A) than on SPC agar containing similar antibiotics but the reverse was observed for forest stream (zone B) samples. Differences between the two media were also observed at individual sample sites. The proportions of strains of AR bacteria resistant to their primary isolation antibiotic varied from 55% (zone B) to 72% in the least polluted Isiokpo and Elele-Alimini streams (zone C), for ampicillin, and mostly < 50% for the other drugs in each zone. Thirty bacterial strains purified from the prevent colonial types on the count media without antibiotics included mainly species of Bacillus (12) and enterobacteria (18). Between five and 10 strains were resistant to > or = three antibiotics; seven were resistant to all five. The antibiograms of most strains were variable and depended on the method of drug application (discs or incorporation into agar), media and temperature of incubation (25 degrees, 37 degrees or 44.5 degrees C). Twenty-one strains were consistently resistant to ampicillin by the two methods; 10 to 19 were consistent for chloramphenicol, tetracycline and penicillin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486567 TI - Leishmaniasis: some recent developments in chemotherapy. PMID- 8486568 TI - Pharmacokinetics of quinolones with special reference to the respiratory tree. AB - Successful treatment of respiratory tract infections with the fluoroquinolones requires knowledge about whether the prescribed antibiotic will reach the site of infection at clinically active concentrations. The difficulty in extrapolating pharmacokinetic information from animal models to man has resulted in new approaches to determine the distribution of antibiotic within the human lung. Bronchoalveolar-lavage (BAL) allows the collection of epithelial-lining-fluid, alveolar macrophages, bronchial mucosal samples and sputum, thereby permitting measurement of the cellular and extracellular concentrations of an antibiotic. All fluoroquinolones show similar patterns of penetration into the lung parenchyma, bronchial mucosa or bronchial secretions. The main differences between these agents concern antibacterial potency and the nature, frequency and severity of adverse reactions. Many respiratory infections are caused by obligate or faculative intracellular pathogens, which are likely to be eradicated by the intracellular and extracellular concentrations of quinolones achieved and is supported by models of phagocytic cell function. PMID- 8486569 TI - The activity of cefpirome and ten other antibacterial agents against 2858 clinical isolates collected from 20 centres. AB - Two thousand eight hundred and fifty-eight aerobic clinical isolates of Enterobacteriaceae, Pseudomonas species, staphylococci, streptococci and Haemophilus species were collected in 19 geographically separated centres in the UK and one in Ireland. The identity of each isolate was confirmed at Southmead Hospital and the MIC of cefpirome, cefotaxime, ceftazidime, cefuroxime, cephradine, amoxycillin, piperacillin, imipenem, gentamicin, ciprofloxacin and trimethoprim was determined by an agar dilution method. Against species of Enterobacteriaceae not associated with producing an inducible cephalosporinase, cefpirome had a similar degree of activity to cefotaxime and was more active than ceftazidime and earlier cephalosporins. Against species with a high prevalence of inducible beta-lactamase production, cefpirome was superior to other cephalosporins; imipenem was also active against these isolates. Cefpirome was active against Pseudomonas aeruginosa, methicillin-sensitive staphylococci, non enterococcal streptococci and Haemophilus spp. When the isolates were exposed to 0.1 mg/L of imipenem in agar plus the test agent, cefpirome had superior activity compared with the other cephalosporins tested for the Enterobacteriaceae, except Proteus vulgaris and Proteus penneri. 8.7% of Enterobacter spp., 7% of Citrobacter spp. and 6.7% of Morganella morganii had susceptibilities to beta lactams suggesting constitutive hyperproduction of chromosomal cephalosporinase; cefpirome, unlike the other cephalosporins tested, was active against these isolates, although to a lesser degree than against the wild-type inducible isolates. No isolates were thought to produce an extended-spectrum beta lactamase. PMID- 8486570 TI - Comparative susceptibility of the Bacteroides fragilis group species and other anaerobic bacteria to meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole. AB - The in-vitro activity of meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole was determined against 395 strains of strict and facultative anaerobes, including Gardnerella vaginalis, Lactobacillus spp. and Mobiluncus spp. The activities of meropenem and imipenem were within one dilution of their MIC50 and MIC90 values. One isolate of Bacteroides fragilis, two of Bacteroides distasonis, and two of Bacteroides ovatus showed resistance or diminished susceptibility to meropenem and imipenem. Metronidazole was active against almost all obligate anaerobic isolates. Some non spore-forming Gram-positive bacilli and lactobacilli were resistant. Ampicillin/sulbactam inhibited almost all isolates at < or = 16/8 mg/L. The activity of clindamycin and cefoxitin was relatively good, but some strains of non-fragilis B. fragilis group species were resistant. Piperacillin was the least active agent tested. PMID- 8486571 TI - The release of endotoxin from antibiotic-treated Escherichia coli and the production of tumour necrosis factor by human monocytes. AB - The influence of antibiotic-induced release of endotoxin from in-vitro grown Escherichia coli on the production of tumour necrosis factor-alpha (TNF) by human monocytes was studied. Antibiotics tested were: cefuroxime (7.5 and 75 mg/L); ceftazidime (10 and 100 mg/L); aztreonam (10 and 100 mg/L); imipenem (10 and 100 mg/L); and tobramycin (8 mg/L). The effect of the combination of cefuroxime plus tobramycin, and the effect of taurolidine, an endotoxin-binding agent, on TNF production was also tested. After incubation for 4 h, all antibiotic-treated cultures (high-dose) induced a similar rise in extracellular TNF production when compared to the controls. However, after incubation for 24 h, a significant rise in TNF production was noticed in the cefuroxime and aztreonam-treated cultures (6440 and 5969 ng/L, respectively) compared to the ceftazidime and imipenem treated cultures (846 and 381 ng/L, respectively). The cefuroxime-induced release of TNF could be reduced by addition of tobramycin (from 6440 to 1615 ng/L). Similar differences in TNF production were noticed in cell-associated TNF. Dose response curves did not demonstrate differences in TNF production in aztreonam or imipenem-treated cultures. However, for both cefuroxime and ceftazidime-treated cultures, low-dose treatment resulted in significantly higher production of TNF. The differences in TNF production between these antibiotics could be explained by the production of filaments following treatment with cefuroxime, aztreonam and low-dose ceftazidime, resulting in late bacterial lysis with high levels of endotoxin, whereas treatment with imipenem or high-dose ceftazidime resulted in the formation of spheroplasts, resulting in early lysis of the bacteria and much lower levels of endotoxin. The addition of taurolidine to either imipenem or aztreonam-treated cultures prevented a rise in TNF production as a result of nearly complete neutralization of the released endotoxin. It was concluded that the observed differences in TNF production by human monocytes in vitro were related to differences in the mechanisms and amount of antibiotic-induced release of endotoxin. PMID- 8486572 TI - Interference by antimalarial drugs with the in-vitro production of reactive nitrogen intermediates by murine macrophages. AB - The production of reactive oxygen intermediates (ROI) by host macrophages has long been recognized as an important defense mechanism against microorganisms. More recently, reactive nitrogen intermediates (RNI), also produced by activated macrophages, have been shown to be part of the host's first line of defense against malaria. In the present in-vitro study we have investigated the effects of antimalarial drugs on RNI production by murine macrophages stimulated by interferon-gamma (IFN-gamma) and/or malaria antigen, and on ROI production induced by phorbol myristate acetate. At concentrations exceeding the peak serum levels achieved with therapeutic dosages, chloroquine, in a dose-dependent manner, inhibited IFN-gamma- and malaria antigen-induced RNI production. Quinine, at a concentration of 10 mg/L also caused a significant reduction in IFN-gamma and malaria antigen-induced RNI synthesis; this concentration was well within the therapeutic range. High concentrations of artelinate significantly inhibited IFN gamma-induced RNI production but clindamycin had no effect on RNI synthesis. In contrast, halofantrine, in concentrations attainable with therapeutic dosages, significantly enhanced IFN-gamma-induced RNI production. ROI production by murine macrophages was unaffected by the antimalarial drugs over the same concentration ranges. It remains to be determined whether these in-vitro effects of antimalarial drugs on RNI production also influence the clinical and parasitological response in patients with malaria. PMID- 8486573 TI - In-vitro susceptibility and in-vivo efficacy of antimicrobials in the treatment of intraabdominal sepsis in mice. AB - Cefoxitin, cefotetan, cefmetazole, ceftizoxime, imipenem plus cilastatin, ampicillin plus sulbactam and clindamycin alone or combined with gentamicin, ciprofloxacin, ofloxacin or aztreonam were compared in the therapy of intraabdominal infection in mice caused by Escherichia coli in combination with either Bacteroides fragilis or Bacteroides thetaiotaomicron. Mortality in the control group was 45%, and no animal receiving either imipenem, gentamicin, ciprofloxacin, ofloxacin or aztreonam died. Mortality in mice receiving cefoxitin, cefotetan, cefmetazole, or ceftizoxime was below 7% (P < 0.05%) and mortality following treatment with ampicillin-sulbactam was 23-27% (P > 0.05). The abscesses were examined ten days after inoculation. No abscesses were observed in mice treated with clindamycin or imipenem. Therapy with gentamicin, ciprofloxacin, ofloxacin, aztreonam or ceftizoxime alone did not prevent abscess formation by both Bacteroides sp. A significant reduction in abscess formation and number of E. coli and B. fragilis was observed with combination therapy of clindamycin with either ciprofloxacin, ofloxacin, aztreonam, or gentamicin and single agent therapy with either imipenem, cefoxitin, cefotetan, cefmetazole and ampicillin-sulbactam alone. However, cefotetan and cefmetazole did not reduce abscess formation or the number of B. thetaiotaomicron. These in-vivo data confirm the in-vitro activity of these antimicrobials. PMID- 8486574 TI - Effectiveness of netilmicin and tobramycin against Pseudomonas aeruginosa in vitro and in an experimental tissue infection in mice. AB - The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing rate (ER) during 3 h of exposure. On the basis of the quantitative relation between E(R) and the drug concentration, the numbers of cfu expected at consecutive times, at constant as well as at declining concentrations, were predicted. The relationship between observed numbers and predicted values of ERt were similar under both conditions for both drugs. On the same basis the numbers of cfu expected in the experimental thigh infection were predicted. There was indeed a significant linear relationship between observed numbers of cfu in homogenized muscle and the values predicted on the basis of the pharmacokinetics of the aminoglycosides, but the slope of this relationship was only 0.22. There was no difference in this respect between the two antibiotics. It is concluded that the efficacy of netilmicin and tobramycin against P. aeruginosa is considerably less in vivo than in vitro, but the relation is about the same for the two drugs; therefore the slightly higher activity of tobramycin in vitro is relevant in the in-vivo situation. PMID- 8486575 TI - Pharmacokinetics of cefuroxime axetil in patients with normal and impaired renal function. AB - The pharmacokinetics of cefuroxime axetil were studied by a model-independent method after a single oral dose corresponding to 500 mg of cefuroxime in 28 subjects grouped according to renal functions. Creatinine clearance (Clcr) was > 85, 50 to 84, 15 to 49, and < 15 mL/min in groups 1, 2, 3, and 4 respectively. The V(area)/F (distribution volume/bioavailability) was independent of renal function, the average being 0.82 +/- 0.27 L/kg. Both Cls/F (systemic clearance/bioavailability) and Clr (renal clearance) decreased linearly with the decrease in Clcr. The T1/2 (serum half-life) was 1.4 +/- 0.33 h, 2.4 +/- 0.65 h, 4.6 +/- 2.32 h, and 16.8 +/- 10.2 h in groups 1, 2, 3, and 4 respectively. A significant correlation existed between kel (elimination rate constant) and Clcr (r = 0.88, P < 0.01). kel of cefuroxime can be predicted by: kel (h-1) = 0.0046 x Clcr + 0.0108. Based on these data, modification of dosing schedule is not deemed necessary when Clcr is above 50 mL/min/1.73 m2, while the standard individual dose should be given every 12 h when Clcr is 49-30 mL/min/1.73 m2, every 24 h when it is 29-10 mL/min/1.73 m2, and every 48 h when it is below 10 mL/min/1.73 m2. PMID- 8486576 TI - Assessment of potential ototoxicity following high-dose nebulized tobramycin in patients with cystic fibrosis. AB - A deterioration in pulmonary function is a common problem in patients with cystic fibrosis. One strategy which might help to arrest this process is the administration of aminoglycosides by nebulizer in dosages which greatly exceed those which are normally given parenterally. Ten patients (4-19 years of age) with cystic fibrosis underwent evoked response audiometry at regular intervals following a 400 mg dose of nebulized tobramycin; the concentrations of tobramycin in samples of blood taken at the same time intervals were also determined. No significant abnormalities in the audiometric investigations were detected. The relationship between shifts in vestibulocochlear potentials and long-term ototoxic sequelae in patients receiving aminoglycosides via a nebulizer requires further evaluation. PMID- 8486577 TI - Recommendations for endocarditis prophylaxis. The Endocarditis Working Party for Antimicrobial Chemotherapy. PMID- 8486578 TI - Coagulase-negative staphylococcal bacteraemia treated with teicoplanin. PMID- 8486579 TI - High rates of erythromycin-resistant Streptococcus pneumoniae among penicillin resistant strains. PMID- 8486580 TI - beta-Lactamase parameters of heterogeneously and homogeneously methicillin resistant Staphylococcus aureus. PMID- 8486581 TI - Problems associated with susceptibility testing of co-amoxiclav. PMID- 8486582 TI - Newer glycopeptide antibiotics tested against nosocomial bloodstream isolates. PMID- 8486583 TI - Activity of four fluoroquinolones against 346 strains of enteric pathogens. PMID- 8486584 TI - HPLC assay of cefixime in serum and CSF. PMID- 8486585 TI - New hazard of meningococcal chemoprophylaxis. PMID- 8486587 TI - Better compliance and medicine use: making it happen. PMID- 8486586 TI - Efficacy of topical ciprofloxacin in the treatment of ear infections in adults. PMID- 8486588 TI - The reemergence of tuberculosis in Arkansas. PMID- 8486589 TI - Patient allegedly abandoned by physicians and hospital. PMID- 8486590 TI - Medical qualification of sport scuba divers. PMID- 8486591 TI - Radiological case of the month. Asbestosis-related round atelectasis. PMID- 8486592 TI - The abrupt discontinuation of fluvoxamine in patients with panic disorder. AB - BACKGROUND: We evaluated patients abruptly withdrawn from fluvoxamine, a serotonin selective reuptake inhibitor, for evidence of a discontinuation syndrome. METHOD: In an open-label study, 14 subjects were abruptly withdrawn from fluvoxamine after treatment lasting 8 months (7 months for 1 patient). Psychological, somatic, and perceptual symptoms were assessed at Day 5, Day 10, and Day 14 postdiscontinuation. Anxiety and depression were assessed using clinician and self-rated scales. RESULTS: Twelve (86%) of 14 subjects developed new symptoms. The most frequent symptoms reported were dizziness/incoordination, headaches, nausea, and irritability. Symptoms peaked on Day 5 postdiscontinuation. Only 1 subject had a recurrence of panic, but another developed anxiety and depression; both were remedicated. CONCLUSION: Abrupt fluvoxamine discontinuation is associated with a characteristic syndrome in many patients. PMID- 8486593 TI - The clinical characteristics of panic disorder in the elderly: a retrospective study. AB - BACKGROUND: Community-based studies of the elderly have observed pathologic levels of anxiety to be common but find low rates of DSM-III-R anxiety disorders. Our clinical experience was that panic disorder may be more common than previously acknowledged. Our goals were to determine the prevalence, clinical characteristics, and possible factors that may facilitate a late-onset of panic disorder. METHOD: The clinical records of 540 patients aged 60 years or more were reviewed. DSM-III-R panic disorder was identified in 51 subjects. Demographic information, current medical illness, and family history were extracted from their records. Rating scale measures of anxiety, depression, phobias, and cognition were available. For comparison, subjects were divided into an early group who experienced onset of panic disorder at age 59 years or earlier and a late group who experienced onset at age 60 years or later. RESULTS: The overall prevalence of panic disorder was 9.4% and late-onset panic was 5.7%. The late onset group experienced more shortness of breath (p = .05) during panic attacks and were more likely to have medical disorders like chronic obstructive pulmonary disease, vertigo, and Parkinson's disease. The early-onset subjects were more socially phobic (p = .008) and more depressed. CONCLUSION: Panic disorder can have onset in late life. Its phenomenology is similar in most respects to that described in young adults. Factors contributing to onset include stress, medical illness, and central nervous system disease. PMID- 8486594 TI - Postpartum obsessive compulsive disorder: a case series. AB - BACKGROUND: The puerperium has typically been a period of risk for the development of psychiatric illness. Although postpartum depressive illness has been discussed extensively in the literature, obsessive compulsive disorder during pregnancy and puerperium has received little attention. METHOD: Fifteen women with new-onset obsessive compulsive symptoms during the puerperium were retrospectively evaluated by chart review; all met DSM-III-R criteria for obsessive compulsive disorder. Distinctive features of their clinical presentation, pharmacotherapy received, and status at 1-year follow-up were recorded. RESULTS: Patients were noted to have a characteristic constellation of symptoms comprised of disabling intrusive obsessional thoughts to harm their babies. Obsessive rituals were not observed in any of the patients described. Patients frequently developed secondary depression and appeared to be exquisitely responsive to serotonin selective reuptake inhibitors. CONCLUSION: The puerperium may be a period of risk for development of new-onset obsessive compulsive disorder. Clinicians caring for puerperal women need to be aware of the impact of these symptoms on maternal and fetal well-being. PMID- 8486595 TI - Rib fractures as an unusual complication of severe tardive dystonia. PMID- 8486596 TI - Molindone and weight loss. PMID- 8486597 TI - Fluoxetine-induced sexual dysfunction and yohimbine. PMID- 8486598 TI - A seizure following bupropion overdose. PMID- 8486599 TI - Role of tyrosine-5 in the cytoplasmic tail of the macrophage asialoglycoprotein receptor in the rapid internalization of ligands. AB - A macrophage asialoglycoprotein binding protein (M-ASGP-BP), which is an endocytic receptor specific for Gal/GalNAc-terminated glycoproteins, was shown to be functionally active as a homooligomer (hexamer or octamer) of a single polypeptide chain of 42 kDa [Ozaki, K., Ii, M., Itoh, N., & Kawasaki, T. (1992) J. Biol. Chem. 267, 9229-9235]. In various endocytic receptors, a four-amino-acid sequence, Tyr-X-Y-Phe, in the cytoplasmic domain has been identified as an internalization signal [Pearse, B.M.F. & Robinson, M.S. (1990) Annu. Rev. Cell Biol. 265, 151-171]. The amino-terminus of the M-ASGP-BP deduced from its cDNA sequence was found to contain the sequence, Tyr5-Glu6-Asn7-Phe8, in its cytoplasmic tail. This was confirmed by the fact that the recombinant M-ASGP-BP isolated from transfected COS-1 cells was found to have the amino-terminal sequence, Thr2-Met3-Ala4-Tyr5-Glu6-Asn7-Phe8. The role of this presumptive internalization signal in the cytoplasmic tail was studied by measuring the endocytic activity of the wild-type and mutant M-ASGP-BPs expressed on COS-1 cells through transfection with the wild-type and mutant cDNAs prepared by oligonucleotide-directed mutagenesis, respectively. On the deletion of Tyr5 or replacement of it with alanine, the internalization of asialoorosomucoid (ASOR) decreased to approximately one-fourth that in the case of the wild-type molecule. On replacement of Tyr5 with phenylalanine, the internalization proceeded at a rate similar to that in the case of the wild-type molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486600 TI - Structure, expression, and evolution of guinea pig serum amyloid P component and C-reactive protein. AB - The structure and expression of the pentraxins, serum amyloid P component (SAP), and C-reactive protein (CRP), have been investigated in the guinea pig. Northern blot analysis of hepatic RNA from animals in which acute inflammation had been induced by intraperitoneal injection of thioglycollate established that neither SAP or CRP is a major acute phase reactant in the guinea pig. Genomic clones of SAP and CRP were isolated and sequenced, and the gene and the derived protein sequences were compared with other mammalian homologues. Both genes have organizations typical of the pentraxin genes of other species, but some differences were defined in the regions that potentially determine the capacity of the pentraxin gene to be induced during acute inflammation. Nucleotide substitutions in coding regions have occurred at similar rates in the two pentraxin genes. Nonsynonymous substitution rates indicate that SAP and CRP are subject to similar, relatively low levels of constraint; at the amino acid sequence level the rate of evolution is approximately two replacements per site per 10(9) years. An estimate of the phylogenetic relationship among the pentraxin genes suggests that SAP and CRP arose as the result of a gene duplication event that occurred very early in mammalian evolution, but subsequent to the divergence of the reptilian ancestors of the mammalian and avian lineages. This raises doubts about the identity of proteins from fish, which have been previously characterized as CRP and SAP. PMID- 8486601 TI - Purification and characterization of prophenoloxidases from pupae of Drosophila melanogaster. AB - Two isoforms of prophenoloxidase were isolated from pupae of Oregon-R strain of Drosophila melanogaster. The purification procedure included ammonium sulfate fractionation, Sephacryl S-200 gel chromatography, DEAE-cellulose, and hydroxylapatite column chromatography. The two isoforms, A1 and A3, could be separated by ammonium sulfate fractionation. The isoelectric points of A1 and A3 were determined to be pH 5.8 and 6.7, respectively. The molecular weights of the monomers of A1 and A3 were estimated by SDS-PAGE to be 78 and 77 kDa, respectively. The native states of A1 and A3 are considered to be homodimeric, as judged by gel-filtration chromatography. PMID- 8486602 TI - A membrane-bound metallo-endopeptidase from rat kidney: its immunological characterization. AB - The structure and location of a membrane-bound metallo-endopeptidase, previously purified from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571], were examined by immunochemical and immunohistochemical methods with a rabbit polyclonal antibody against the purified enzyme. On treatment with endoglycosidase F, the subunit of the purified enzyme (molecular mass = 88 kDa) was converted to a smaller form (78.5 kDa), indicating that the enzyme contained at least 11% N-linked carbohydrate. Treatment of kidney membranes with papain resulted in release of the enzyme, as shown by Western blotting analysis of the solubilized fraction. Immunoassays of rat tissues showed that only the kidney, and small and large intestine expressed significant amounts of the antigen. Moreover, immunohistochemical studies showed that the antigen was confined to the luminal surfaces of the proximal renal tubules and the intestinal villi. Thus, like another kidney membrane metallo-endopeptidase, meprin [Kounnas et al. (1991) J. Biol. Chem. 266, 17350-17357], the purified enzyme is shown to be a glycoprotein that is probably anchored in the plasma membrane, and located in the luminal surface of microvillar membranes of the kidney and intestine. These results indicate that our enzyme and meprin have clear structural and topological similarities. PMID- 8486603 TI - Drift of the sialyl-linkage specific recognition of the sialidase of influenza B virus isolates. AB - Sialyl-linkage specificity of the sialidase of influenza B viruses isolated in different years from 1940 through 1990 (B/Lee/40,B/Setagaya/3/56,B/Tokyo/7/66,B/Kagoshima/1/68, B/Gifu/2/73, B/Kanagawa/3/76, B/Ibaraki/2/85, B/Yamagata/16/88, and B/Bangkok/163/90) was studied with N-acetylneuraminyl (alpha 2-3)- and (alpha 2-6)-lactoses, GM3 gangliosides containing the same sialyl-oligosaccharide sequences as sialyllactose, and also with type I and type II lacto-series gangliosides carrying Neu5Ac alpha 2-3Gal and NeuAc alpha 2-6Gal linkages as substrates. From an examination of up to nine strains, the sialidases of all viruses preferentially hydrolyze substrates with Neu5Ac alpha 2-3Gal linkage rather than the Neu5Ac alpha 2-6Gal linkage. It was found that the sialidase activity toward Neu5Ac alpha 2-6Gal linkage relative to Neu5Ac alpha 2-3Gal linkage is increased in later strains, whether sialyllactose or ganglioside is used as the substrate. These results suggested that the sialidase of influenza B virus isolates has shown a drift in linkage specificity which correlates with the year of isolation. PMID- 8486604 TI - Purification of a 60 kDa nuclear localization signal binding protein in rat liver nuclear envelopes and characterization of its properties. AB - A nuclear localization signal binding protein in nuclear envelope was studied as the first step to determine the mechanism of nuclear protein recognition by nuclear envelope. The rat liver nuclear envelope extract was resolved by SDS-PAGE and ligand blotted with 125I-labeled nucleoplasmin bearing a strong nuclear localization signal. A nuclear localization signal binding protein with molecular mass of 60 kDa (NBP60) was detected in the extract. NBP60 could be extracted with 2% Triton X-100-1 M KCl but not with 1 M KCl, 2 M urea, or 2% Triton X-100. The protein was partitioned to the lower layer in a two phase system using Triton X 114. These results suggested that the protein is an intrinsic membrane protein and has a hydrophobic surface. This protein was bound to not only nucleoplasmin but also the nuclear localization signal peptide of SV 40 large T-antigen (T peptide) conjugated to human serum albumin. The binding of NBP60 to nucleoplasmin Sepharose was inhibited by 50% in the presence of 0.12 mM T-peptide. However, a high concentration of 2.1 mM was necessary, when mutant T-peptide in which the essential amino acid lysine was substituted with threonine was used. These results suggested that NBP60 binds specifically to nuclear localization signals. NBP60 extracted from the nuclear envelope was purified by nucleoplasmin-Sepharose affinity chromatography following hydroxyapatite high performance liquid chromatography. PMID- 8486605 TI - Structure of 29-kDa protein from ascidian (Halocynthia roretzi) body wall muscle. AB - Preparations of thin filament from ascidian (Halocynthia roretzi) body wall muscle were found to be contaminated with large amounts of an unknown protein which, when purified, migrated to 29 kDa on SDS-PAGE and was thus named HR-29. To elucidate its physiological function, we have determined the primary structure of HR-29 by peptide and cDNA sequence analysis. Genomic sequence analysis showed that HR-29 is divided to four exons by three introns. It is composed of 251 amino acid residues and the N-terminal Ser is blocked by an acetyl group. The N terminal domain of 150 residues is hydrophilic, and from residue 36 to 92 there are three similar repeated sequences of 19 residues. The N-terminal domain showed no significant sequence homology with other proteins. On the other hand, the C terminal domain of 100 residues has homology with those of small heat-shock proteins and alpha-crystallin of lens protein. HR-29 is thought to be a fusion protein of two different origins. Recently alpha B-crystallin was identified in skeletal muscle and suggested to be a myofibril-stabilizing protein [Atomi, T. et al. (1991) J. Biochem. 110, 2360-2364]. Thus, HR-29 may also be a myofibril stabilizing protein, as suggested by the sequence similarity of the C-terminal domain with alpha-crystallin, although the origin and role of the N-terminal domain are not clear. PMID- 8486606 TI - Characterization of casein kinase II, and of p98 as one of its effective phosphate acceptors in sea urchin eggs. AB - CK-II has been partially purified from a 1.5 M KCl extract of unfertilized sea urchin eggs by means of DEAE-cellulose column chromatography, gel filtration on Sephacryl S300, and heparin-agarose column chromatography, successively. This partially purified CK-II was associated with a 98 kDa polypeptide (designated as p98), which was then separated from the kinase by Mono Q column chromatography (HPLC). The biochemical characteristics of CK-II purified from unfertilized eggs were similar to those of CK-IIs from various mammalian cells: requirements of divalent cations (Mg2+ and Mn2+) and phosphate acceptors (casein and p98), response to basic polypeptides and heparin, subunit structure and molecular size. Moreover, it was found that: (i) p98 (apparent pI 10.0) has DNA-binding ability and functions as an effective phosphate acceptor for CK-II in vitro; (ii) phosphorylation of p98 by the kinase was highly stimulated by histone-like sperm protein from sea urchin sperm, protamine (salmon sperm), and poly Arg; and (iii) selective phosphorylation of p98 by CK-II was detected when the DEAE-cellulose fraction from unfertilized eggs was incubated with [gamma-32P]ATP in the presence of protamine. Some biochemical characteristics of p98 from the eggs were similar to those of transcriptional factor Sp1. The evidence obtained suggests that (i) arginine-rich sperm proteins function as potent activators for CK-II in unfertilized eggs and (ii) specific phosphorylation of p98 by the activated kinase may play an important role in the transcriptional regulation in the eggs accompanying fertilization. PMID- 8486607 TI - Thermostable farnesyl diphosphate synthase of Bacillus stearothermophilus: molecular cloning, sequence determination, overproduction, and purification. AB - The structural gene for thermostable farnesyl diphosphate synthase from Bacillus stearothermophilus was cloned, sequenced, and overexpressed in Escherichia coli cells. A 1,260-nucleotide sequence of the cloned fragment was determined. This sequence specifies an open reading frame of 891 nucleotides for farnesyl diphosphate synthase. The deduced amino acid sequence shows a 42% similarity with that of E. coli FPP synthase [Fujisaki et al. (1990) J. Biochem. 108, 995-1000]. Comparison with prenyltransferases from a wide range of organisms, from bacteria to human, revealed the presence of seven highly conserved regions. In contrast to thermolabile prenyltransferases, which have four to six cysteine residues, the thermostable farnesyl diphosphate synthase carries only two cysteine residues. This enzyme is also unique in that some of the amino acids that are fully conserved in equivalents from other sources are replaced by functionally different amino acids. Construction of an overproducing strain provided a sufficient supply of this enzyme and it was purified to homogeneity. The purified recombinant enzyme is immunochemically identical with the native B. stearothermophilus enzyme, and it is not inactivated even after treatment at 65 degrees C for 70 min. PMID- 8486608 TI - Structure and expression of the gene encoding rat nonspecific form delta aminolevulinate synthase. AB - To understand the regulatory mechanisms controlling the heme biosynthetic pathway in animal liver, RNA blot hybridization analysis was used to examine the developmental stage-specific transcription of the gene encoding nonspecific form delta-aminolevulinate synthase (ALAS-N). The expression of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) mRNA was also studied. The results demonstrated that, while ALAS-E is the key enzyme which supplies large quantities of heme for hemoglobin synthesis in fetal rat liver, ALAS-N functions to supply heme for the cytochrome P-450 system in fetal, newborn, and adult rat liver. ALAS N was also suggested to work as a housekeeper gene to supply heme for respiratory cytochromes and other hemoproteins in various tissues. The structure and organization of the rat ALAS-N gene were next analyzed to study the molecular mechanisms regulating ALAS-N gene transcription. The ALAS-N gene was found to span more than 14 kb in the rat genome, encompassing eleven exons. The promoter region of the gene was found to contain several potential cis-acting regulatory elements, including motifs matching the TATA box sequence and the nuclear respiratory factor 1 binding sequence. The organization of the rat ALAS-N gene was determined to be quite similar to that of the ALAS-E gene in mouse; the mouse ALAS-E gene consists of eleven exons. This observation suggested that the ancestral gene for ALA synthase in animals was probably composed of eleven exons, and both the ALAS-N and ALAS-E genes were derived from this ancestral gene. PMID- 8486609 TI - Low-density lipoprotein receptor mutation that deletes exons 2 and 3 by Alu-Alu recombination. AB - A deletion mutant in the low density lipoprotein receptor gene of a Japanese patient with heterozygous familial hypercholesterolemia was analyzed. Genomic Southern blotting showed abnormal size restriction fragments with BamHI (7.8 kb), EcoRI (3.8 kb), BglII (17 kb), KpnI (> 23 kb), EcoRV (13 kb), and XbaI (14 kb). The abnormal EcoRI fragment, 3.8 kb, was cloned into lambda phage vector, and the deleted region of 10 kb including exons 2 and 3 was identified. The nucleotide sequence around the deletion joint was determined. The sequence of the eight nucleotides in the deletion-joint region of the mutant gene was identical to the corresponding sequences of both introns 1 and 3 of the normal gene. The deletion seemed to occur by an unequal recombination between the Alu-like sequences in the same direction in introns 1 and 3. PMID- 8486610 TI - Purification and characterization of a nuclear pore glycoprotein complex containing p62. AB - It is known that nucleoporins, a family of glycoproteins with N-acetylglucosamine that are found in nuclear pore complexes, are essential for nuclear import and export. A major component of the family, p62, was purified from a salt extract of rat liver nuclear envelopes by wheat germ agglutinin-Sepharose affinity chromatography and DEAE-anion exchange HPLC. p62 was purified as a complex with two glycoproteins of 60 and 54 kDa. The presence of the complex was confirmed by gel filtration, glycerol density gradient centrifugation, and cross-linking experiments. The molecular ratio of the 62-, 60-, and 54-kDa components of the complex was estimated to be 1: 1.1 +/- 0.2: 1.7 +/- 0.3 from the intensity of Coomassie Blue staining of SDS-PAGE gels. The complex was stable against 1 M NaCl, 1% Triton X-100, and 2 M urea. The Stokes' radius and sedimentation coefficient of the complex are 8.0 nm and 6.7 S. The molecular mass and frictional ratio of the complex were estimated to be about 231 kDa and 2.0, respectively. p62 and p54 were acidic and neutral proteins, respectively, exhibiting charge heterogeneities, and p60 was assumed to be a basic protein. p60 tended to undergo proteolytic degradation to a 47-kDa fragment. PMID- 8486611 TI - Structural changes in Z-disks of skeletal muscle myofibrils during growth of chicken. AB - Postnatal structural changes in Z-disks of skeletal muscles of chicken from 2 to 35 wk after hatching were examined to elucidate how Z-disks develop from the embryonic to the mature stage. The mechanical strength of Z-disks of breast muscle (i.e. the ratio of the number of myofibrils to the total number of myofibrils and myofibrillar fragments composed of 1-4 sarcomeres, which were formed under the mechanical forces exerted during homogenization) increased from 66% at 2 wk of age to 75% at 10 wk, and leveled off at 76% at 25 wk. The Z-disks of leg muscle were stronger than those of breast muscle throughout growth. Measurements by electron microscope showed that the width of Z-disks increased during growth from 26 to 33 nm, 48 to 53 nm, and 89 to 101 nm, in white, intermediate, and red muscle fibers, respectively. It was proved that the configuration of Z-filaments, the structural backbone of Z-disks, takes its final shape within 2 wk after hatching; the immature Z-disks are then reinforced by the accumulation of amorphous matrix materials. These results confirm that the maturation of Z-disks is brought about by physical motion in muscle tissue and the accompanying development of tension. PMID- 8486612 TI - Purification and processing of rat liver procathepsin B. AB - In order to characterize the intracellular processing event of lysosomal cathepsin B, the proenzyme was purified from the rat liver microsomal contents using a Con A-Sepharose column, a Sepharose-Gly-Phe-GlySc column, and an anti cathepsin B IgG column. The purified proenzyme gave a single protein band of 39 kDa on SDS/polyacrylamide gel electrophoresis. The proenzyme showed no appreciable enzymatic activity. When the purified proenzyme was incubated with the cathepsin B-free tritosomal contents, prepared by treatment of the tritosomal contents with anti-cathepsin B IgG Sepharose, at pH 3.0, 30 degrees C, a remarkable increase of enzymatic activity was observed. Immunoblot analysis showed that the proenzyme was completely converted to the active intermediate form of 31 kDa after 1 h incubation. These processing and activation events were blocked in the presence of pepstatin. When the proenzyme was incubated with the cathepsins B- and D-free tritosomal contents, prepared by treatment of the cathepsin B-free tritosomal contents with anti-cathepsin D IgG Sepharose, the processing and activation did not occur. These results indicate that cathepsin D is involved in the processing and activation of procathepsin B in rat liver lysosome. In the NH2-terminal sequence analysis of the 31 kDa form, the terminal was assigned as proline (66th residue). Since the NH2-terminus of the mature single-chain form of cathepsin B (29 kDa) ends at leucine (80th residue), the NH2 terminus of the 31 kDa form is 14 amino acid residues longer than that of the single-chain form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486613 TI - Erythropoietin 5'-flanking sequence-binding protein induced during hypoxia and cobalt exposure. AB - The 5'-flanking region of the human erythropoietin (Epo) gene contains a 0.14-kb sequence that is conserved in the Epo gene from mouse and located within a promoter that is activated under hypoxic conditions such as anemia. Using a fragment containing this sequence in DNA mobility shift assays, we found that specific DNA-binding proteins were induced in mouse kidney nuclei under anemic hypoxia. Using synthetic double-stranded oligonucleotides that contain this sequence, the essential binding site was defined to be the -40 to -20 region upstream of the transcription initiation site in the human Epo gene. By DNA affinity chromatography using a column with the immobilized 5'-flanking sequence, two inducible binding proteins with apparent molecular masses of 55 and 45 kDa were identified in the nuclei of mouse kidney and liver under anemic hypoxia. These binding proteins were also induced during cobalt exposure. PMID- 8486614 TI - Cloning of the DNA polymerase gene of Bacillus caldotenax and characterization of the gene product. AB - The pol gene of the thermophilic eubacterium Bacillus caldotenax was cloned in a plasmid and expressed in Escherichia coli. The PCR method was used to clone the gene with no previous knowledge of the gene or protein sequence. The 3,329-bp DNA fragment containing the structural gene for DNA polymerase was sequenced. DNA polymerase, as deduced from the DNA sequence, consisted of 877 amino acids, had a molecular weight of 99,452, and was structurally homologous to the DNA polymerases of the Pol I family (family A), which includes E. coli DNA polymerase I and T7 DNA polymerase. B. caldotenax DNA polymerase (Bca polymerase) purified from the recombinant E. coli strain was characterized. Like E. coli Pol I, Bca polymerase had 5'-->3' exonuclease activity. The degraded product with the molecular weight of 65,000 was also purified and found to have polymerase activity. To overproduce this Klenow-type fragment of Bca polymerase, a recombinant expression plasmid pUI205 with a deletion in the 5'-region of the pol structural gene was constructed. The DNA polymerase produced by pUI205 is more suitable for use in the dideoxy sequencing method than the other DNA polymerases that have been used for sequencing. PMID- 8486615 TI - Structural requirements for the interaction of p21ras with GAP, exchange factors, and its biological effector target. AB - From the multitude of mutations that have been tested in p21ras, a common theme emerges regarding its interaction with the effector target, GAPs, and the newly discovered exchange factors. Many of the mutations that result in dysfunction for all three types of interactions are localized to the switch 1 and switch 2 regions of the p21ras three-dimensional structure (Fig. 2). These two regions change conformation on GTP binding by p21ras and, accordingly, both GAP binding and Ras biological activity are GTP-dependent processes. In addition, certain mutations in the switch 1 and 2 regions alter the affinity of GAP for p21ras, again implicating this region in the binding interaction. On the other hand, the SDC25 exchange factor appears to promote dissociation of both GTP and GDP from p21ras, suggesting that the overall conformation of the switch 1 and 2 regions may not be important for recognition by SDC25. Moreover, none of the switch 1 or 2 mutations that impaired stimulation by SDC25 affected its binding to p21ras. This suggests that these residues are essential for the mechanism of activation by SDC25 but not for its binding to p21ras. Amino acids at positions 73, 75, and possibly 102 and 103 appear also to be involved in the activation of p21ras by exchange factors. Whether these are required for binding to the exchanger has not been reported. PMID- 8486616 TI - The Wilms' tumor gene product WT1 activates or suppresses transcription through separate functional domains. AB - We recently reported that the putative tumor suppressor gene product WT1 interacts with a 5'-flanking DNA sequence 5'-GCGGGGGCG-3' within the platelet derived growth factor A-chain gene and abolishes its promoter activity, suggesting that WT1 functions as a transcriptional suppressor of the platelet derived growth factor A-chain gene. We now show that WT1 functions also as a transcriptional activator. Using chimeric reporter plasmids, we demonstrated that WT1 requires both 5' and 3' binding sites relative to transcription start site for transcriptional repression; however, when WT1 binds to either the 5' or the 3' site alone, WT1 functions to activate transcription. We truncated the wt1 gene and established that amino acid residues 84-179 are required for transcriptional suppression, whereas amino acid residues 180-294 contain a domain that mediates transcriptional activation. These results establish that WT1 has regulatory domains that function either to activate or suppress transcription and suggest the possibility that WT1 functions as an activator and not as a suppressor of selected gene transcription. PMID- 8486617 TI - The coated vesicle vacuolar (H+)-ATPase associates with and is phosphorylated by the 50-kDa polypeptide of the clathrin assembly protein AP-2. AB - We have previously noted a 50-kDa polypeptide (p50) co-purifying with preparations of the bovine brain clathrin-coated vesicle vacuolar (H+)-ATPase (V ATPase) (Zhang, J., Myers, M., and Forgac, M. (1992) J. Biol. Chem. 267, 9773 9778). We show that p50 is also immunoprecipitated with the V-ATPase, further suggesting its specific association with the proton pump. To determine the identity of this 50-kDa polypeptide and the stoichiometry of its association with the V-ATPase, we performed N-terminal amino acid sequencing and quantitative amino acid analysis of the gel-purified protein. These results revealed the unknown polypeptide to be the 50-kDa subunit of the clathrin assembly protein AP 2 (AP50); we estimate the stoichiometry of association is one AP50 per V-ATPase complex. AP50 is an N-ethylmaleimide (NEM)-inhibitable autokinase and incubation of purified V-ATPase with [gamma-32P]ATP resulted in the NEM-sensitive phosphorylation of AP50 and the B subunit of the V-ATPase. The same phosphorylation pattern is seen if the labeling reaction is done with intact clathrin-coated vesicles and the V-ATPase subsequently immunoprecipitated from the solubilized vesicles. This represents the first report of phosphorylation of one of the V-ATPase subunits. The functional significance of this phosphorylation for regulation or targeting of the V-ATPase in vivo remains to be determined. PMID- 8486618 TI - Insulin action on the internalization of the GLUT4 glucose transporter in isolated rat adipocytes. AB - A novel method was developed to measure relative amounts of the GLUT4 glucose transporter on the surface of intact fat cells and to monitor the action of insulin on cell surface glucose transporters as they internalize into intracellular membranes. The method takes advantage of two predicted trypsin cleavage sites in the major exofacial loop of this transporter protein. Treatment of cyanide-poisoned rat adipocytes with 1 mg/ml trypsin at 37 degrees C for 30 min produced an immunoreactive GLUT4 protein species in subsequently isolated plasma membranes that migrated with higher mobility (apparent M(r) = 35,000) than native GLUT4 (apparent M(r) = 46,000) on SDS-polyacrylamide gel electrophoresis. This proteolyzed GLUT4 protein was absent in the intracellular low density microsomes. Insulin treatment of adipocytes for 20 min prior to sequential additions of cyanide and trypsin caused a 16-fold increase in the proteolytically cleaved GLUT4 species. Incubation of fresh fat cells with trypsin caused a rapid and progressive appearance of the proteolyzed GLUT4 species in the intracellular low density membranes as well as plasma membranes. After 5 min of trypsinization, 66% of the total cleaved GLUT4 in these cells had moved into the low density membranes. Insulin treatment markedly decreased the internalized cleaved GLUT4 to 20% of the total. These data indicate the following: 1) trypsinization of the GLUT4 transporter protein on intact fat cells is a convenient means to monitor the extent of transporter recruitment to the plasma membrane by insulin, as well as to estimate GLUT4 internalization rates; and 2) the action of insulin on glucose transporter redistribution to the cell surface is associated with a marked inhibition of the fraction of cell surface GLUT4 transporters internalized per unit time. PMID- 8486619 TI - Presteady state kinetics of an S-adenosylmethionine-dependent enzyme. Evidence for a unique binding orientation requirement for EcoRI DNA methyltransferase. AB - We present the first presteady state kinetic analysis of an S-adenosylmethionine dependent enzyme. The target enzyme is the bacterial EcoRI DNA methyl transferase, which transfers the methyl group to the second adenine in the DNA sequence GAATTC. The rate constant for conversion of the central complex (enzyme DNA-S-adenosylmethionine) to products (enzyme-methylated DNA-S adenosylhomocysteine) (41 +/- 7 s-1) is over 300-fold faster than kcat, consistent with our demonstration that steps after methyl transfer are rate limiting (Reich, N. O., and Mashhoon, N. (1991) Biochemistry 30, 2933-2939). Methyl transfer at the N6 amino moiety of adenine on each strand requires a single binding orientation. PMID- 8486620 TI - Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. AB - Indolocarbazoles have been identified as novel inhibitors of protein kinase C (PKC), with Go 6976 as one of its most potent and selective representatives. Recombinant PKC isozymes alpha, beta 1, delta, epsilon, and zeta were used in in vitro kinase assays to investigate Go 6976 with respect to isozyme-specific PKC inhibition. Go 6850, identical with GF 109203X, another PKC-specific kinase inhibitor, was included in this study as a reference compound. Nanomolar concentrations of the indolocarbazole Go 6976 inhibited the Ca(2+)-dependent isozymes alpha and beta 1, whereas even micromolar concentration of Go 6976 had no effect on the kinase activity of the Ca(2+)-independent PKC subtypes delta, epsilon, and zeta. In contrast, the bisindolymaleimide Go 6850 inhibited all PKC isozymes, however, with a ranked order of potency (alpha > beta 1 > epsilon > delta > zeta). Kinetic analysis revealed that PKC inhibition by Go 6976 was competitive with respect to ATP, non-competitive with respect to the protein substrate, and mixed type with respect to phosphatidylserine. Further experiments in the presence of different amounts of free Ca2+ indicated that interference with Ca2+ or its binding site is not responsible for the differential inhibition of PKC isozymes by Go 6976. PMID- 8486621 TI - Characterization of retinol metabolism in cultured human epidermal keratinocytes. AB - Retinoids present in cultured human epidermal keratinocytes maintained in medium containing 25 nM retinol were identified and quantitated utilizing reverse-phase gradient high performance liquid chromatography. Total cell retinoid mass and composition averaged 12.59 pmol/mg cell protein +/- 1.86, (mean +/- S.D., n = 5) between strains and was constant with culture age. Long chain fatty acid esters of retinol and 3,4-didehydroretinol comprised greater than 95% of total retinoid, each contributing 77 and 23% of total esters, respectively. In mature stratified cultures, less abundant retinoids included unesterified retinol, 1%, and 3,4 didehydroretinol, 0.5%, retinoic acid, 0.5%, and a retinoid not previously reported in mammalian cells, 3,4-didehydroretinoic acid, 0.3%. This absolute and relative retinoid composition was essentially constant with culture age except that 3,4-didehydroretinoic acid was not detected in 3-4-day-old cultures (16-32 cell colonies), suggesting that keratinocyte differentiation may be related to endogenous changes in production of "active" retinoids. Separate pools of retinyl and 3,4-didehydroretinyl esters served as predominant sources of substrate for production of retinoic and 3,4-didehydroretinoic acids, respectively, suggesting that their production may be regulated independently. PMID- 8486622 TI - Trypanosome metabolism of myristate, the fatty acid required for the variant surface glycoprotein membrane anchor. AB - The trypanosome variant surface glycoprotein (VSG) is anchored to the outer leaflet of the parasite plasma membrane by a glycosyl phosphatidylinositol (GPI). The VSG anchor is unique among GPIs in containing exclusively dimyristoylglycerol as its lipid moiety. Myristate is incorporated into the anchor precursor by sequential deacylation and specific reacylation with myristate. Although myristate is required for the VSG anchor, trypanosomes cannot synthesize this fatty acid and must import their entire supply from the host bloodstream, where it exists in low abundance. Chemical analysis of these parasites reveals that most of their myristate is in VSG protein, with no major lipid storage form. Unexpectedly, when these cells are radiolabeled with [3H]myristate in culture, most of the label is incorporated into phospholipids, with little into VSG. This apparent contradiction is explained by the fact that trypanosomes in culture medium elongate much of the [3H]myristate into palmitate and stearate, probably because the medium (with only 5% serum) contains limiting amounts of these fatty acids. In contrast, trypanosomes radiolabeled in whole blood (with higher concentrations of palmitate and stearate) do not modify most of the [3H]myristate, and instead utilize the major portion of it for GPI synthesis. Our studies suggest that bloodstream trypanosomes have evolved highly efficient means of directing myristate into the GPI biosynthetic pathway. PMID- 8486623 TI - Effect of low molecular weight aliphatic alcohols and related compounds on platelet factor 4 subunit association. AB - Titration of platelet factor 4 (PF4) with increasing concentrations of various low molecular weight aliphatic alcohols disrupts dimer and tetramer quaternary structure while preserving tertiary structural integrity. Normally observed slow subunit exchange (1H NMR time scale) is shifted into the fast chemical exchange regime. The order of effectiveness is butanol > 2-propanol > propanol > ethanol > methanol. Fluorination of ethanol (trifluoroethanol) and 2-propanol (hexafluoro-2 propanol) increases effectiveness by approximately 2 orders of magnitude. Oxidation to 2-propanone or trifluoro-2-propanone produces a less effective compound, suggesting a mechanistic role for the hydroxyl group. Increasing the number of hydroxyls to three, as in glycerol, however, is relatively ineffective in disrupting aggregate states or modifying subunit exchange rates. While 19F NMR studies indicate that these alcohols specifically interact with PF4, binding alone can not explain their mechanism of action. Dimethyl sulfoxide, structurally similar to 2-propanol, disrupts PF4 aggregation by direct binding, but does not shift subunit exchange kinetics into the NMR fast-exchange regime. Although not fully understood, the effectiveness of these compounds appears to be related to the colligative properties of the solution. PMID- 8486624 TI - Isolation and primary structure of the three major forms of granulin-like peptides from hematopoietic tissues of a teleost fish (Cyprinus carpio). AB - Granulins are cysteine-rich polypeptides purified from human and rat hematopoietic cells and structurally related to the epithelin family of growth modulatory factors. A prototypic form of granulin was isolated from the hematopoietic organs of teleost fish (Belcourt, D., and Bennett, H.P.J. (1988) J. Cell Biol. 107, 629 (abstr.)). This study reports the structure of three granulins purified from the spleen and head kidney of the carp (Cyprinus carpio). Ion-spray mass spectrometric analysis of granulin-1, -2, and -3 corroborated the observed primary structures and demonstrated that each 57-residue-peptide was monomeric in nature with all cysteines linked via intramolecular disulfide bridges. A comparison of the carp granulin sequences demonstrates that granulins 2 and 3 are most closely related with sequence variations occurring primarily toward the amino terminus. A rabbit polyclonal antibody was raised against carp granulin-1 to develop a radioimmunoassay for this peptide, which showed no significant cross-reactivity with granulin-2 and -3. The distribution of carp granulin-1 was studied by screening purified tissue extracts for immunoreactivity using reversed-phase high performance liquid chromatography. A single form of immunoreactive granulin-1 was identified in all carp tissues studied including spleen, head kidney, heart, skin, gills, and gut. These studies have established that members of the granulin/epithelin family are found in a lower vertebrate and may serve important growth modulatory functions throughout the vertebrate kingdom. PMID- 8486625 TI - Two different, overlapping pathways of transcription initiation are active on the TATA-less human androgen receptor promoter. The role of Sp1. AB - In this study, the minimal promoter requirements of the TATA-less human androgen receptor (hAR) gene promoter are described. The hAR promoter is characterized by a short GC-box (-59/-32) and a long homopurine stretch (-117/-60). Two major transcription initiation sites, AR transcription initiation site I (AR-TIS I, (+1/2/3)) and AR transcription initiation site II (AR-TIS II, (+12/13)) are located in a 13-base pair region (Faber, P. W., van Rooij, H. C. J., van der Korput, J. A. G. M., Baarends, W. M., Brinkmann, A. O., Grootegoed, J. A., and Trapman, J. (1991) J. Biol. Chem. 266, 10743-10749). Transient transfection of COS cells with hAR promoter deletion and mutant constructs, followed by RNA isolation and S1 nuclease protection analysis showed that the process of transcription initiation through AR-TIS I and AR-TIS II is regulated by different promoter sequences. The GC-box directed initiation from AR-TIS II but did not affect AR-TIS I utilization, which is dependent upon sequences between positions 5 and +57. Band shift analysis identified the transcription factor Sp1 as the protein interacting with the GC-box. A single Sp1 binding sequence was found to be present in the GC-box. Footprint analysis confirmed the interaction of Sp1 with this sequence. The differential initiation through AR-TIS I and AR-TIS II was substantiated by the introduction of point mutations in the Sp1 binding sequence: only mutations that specifically abolished Sp1 binding interfered with AR-TIS II utilization, but all mutations left AR-TIS I initiation intact. PMID- 8486626 TI - Glycoprotein recycling to the galactosyltransferase compartment of the Golgi complex. AB - The recycling of plasma membrane glycoproteins to the Golgi complex is well established, but it is not clear which Golgi subcompartments receive this traffic. To date, recycling into the trans-Golgi compartment that contains sialyltransferase and the early Golgi region that contains alpha-mannosidase I has been demonstrated. However, transport into other Golgi compartments has not been reported. In this study we tested the return of cell surface glycoproteins to the Golgi galactosyltransferase compartment using the ldlD mutant of Chinese hamster ovary cells. The cation-independent mannose 6-phosphate/insulin-like growth factor-II receptor recycled through this Golgi region with a half-time of 4 h and was transported to the sialyltransferase compartment as well. Because galactosyltransferase and sialyltransferases are probably located in different trans-Golgi regions in Chinese hamster ovary cells, these results suggest that the two compartments each receive recycling traffic or that recycling glycoproteins enter one region and are then transported to the other. The extent of cell surface protein recycling through the galactosyltransferase compartment was also studied. At least 10 different glycoproteins were transported from the cell surface to this Golgi region. Moreover, our results suggest that recycling glycoproteins make up 12-25% of the flux of cell surface glycoproteins through the Golgi galactosyltransferase compartment; the balance is comprised of newly made glycoproteins. PMID- 8486627 TI - Identity elements of tRNA(Trp). Identification and evolutionary conservation. AB - In this study, the varying reactivities of Bacillus subtilis tryptophanyl-tRNA synthetase toward prokaryotic, eukaryotic, and halophile tRNAs were employed to define the potential identity elements on tRNA(Trp). On this basis mutagenesis was performed to obtain, through in vivo heterologous expression in Escherichia coli and in vitro transcription with T7 RNA polymerase, mutant B. subtilis tRNA(Trp) for comparison with the wild-type. These comparisons served to establish G73 and the anticodon as major identity elements, and A1-U72, G5-C68, and A9 as minor identity elements. While the tryptophanyl-tRNA synthetase from B. subtilis and E. coli require G73 to function, replacement of G73 by A73 favors the enzyme from yeast. This change points to the variation of the identity elements for the same amino acid among different organisms. The similarity in these elements between B. subtilis and E. coli tryptophanyl-tRNA synthetase, however, suggests that identity elements on tRNA, like the active centers on enzymes, undergo evolutionary change at slower rates than less essential portions of the macromolecule. PMID- 8486628 TI - Kinetic characterization of a beta-glucosidase from a yeast, Candida wickerhamii. AB - The extracytoplasmic, cell-bound beta-1,4-glucosidase of Candida wickerhamii was characterized kinetically. The enzyme was found to produce glucose from cellobiose and cellodextrins (degree of polymerization from three to six) by catalyzing the removal of the terminal glucose moiety from the nonreducing end of these beta-glucans. The Km values for the series, cellobiose through cellohexaose, were 210.7, 106.6, 106.3, 105.9, and 79.8 mM, respectively, whereas the kcat values were 14.79, 13.24, 13.78, 15.13, and 7.66 mumol of glucose.min 1.mg-1 of protein, respectively. A computer program was developed to estimate the integrated rate equation. When the above kinetic constants were used in the computer model, the predicted rates of glucose formation agreed well with the experimental data. Saccharomyces cerevisiae, which is unable to ferment cellobiose or cellodextrins, ferments glucose about twice as fast as C. wickerhamii. If S. cerevisiae is cultured on cellobiose or cellodextrins and the purified C. wickerhamii beta-glucosidase is added to the S. cerevisiae culture at levels that mimic the production of beta-glucosidase by a C. wickerhamii culture with time, the two cultures produce ethanol at equivalent rates. This suggests that the rate-limiting step in the fermentation of cellobiose/cellodextrins by C. wickerhamii is the production of beta-glucosidase. PMID- 8486629 TI - Phosphate affects the distribution of flux control among the enzymes of oxidative phosphorylation in rat skeletal muscle mitochondria. AB - The flux control coefficients of adenine nucleotide translocase, the phosphate transporter, and H(+)-ATPase were determined in rat skeletal muscle mitochondria using glutamate plus malate as substrates and soluble F1-ATPase as load enzyme. It was observed that the flux control coefficients of adenine nucleotide translocase, H(+)-ATPase, and the load enzyme F1-ATPase, at comparable rates of respiration, strongly depend on the phosphate concentration in the incubation medium. So, the flux control exerted by adenine nucleotide translocase, in the intermediate states of mitochondrial respiration (approximately 120 nmol of O2/min/mg) at 10 mM phosphate, was found to be about 0.37. At a phosphate concentration of 1 mM and comparable rates of respiration the flux control coefficient of the translocase decreased to about 0.20. Under these conditions, a sharp increase in the controlling influence of H(+)-ATPase from 0.10 to 0.74 was detected. Furthermore, at this flux rate, the sum of flux control coefficients of adenine nucleotide translocase, H(+)-ATPase, phosphate transporter, and the load enzyme F1-ATPase was noted to be very close to unity. This indicates that under the conditions of intermediate state respiration, all of the other reactions have a negligible controlling influence on oxidative phosphorylation in skeletal muscle mitochondria. PMID- 8486630 TI - Temperature-sensitive mutations in the phage P22 coat protein which interfere with polypeptide chain folding. AB - Temperature-sensitive mutations in the coat protein of phage P22 severely restrict formation of infectious particles at restrictive temperature. A set of 25 temperature-sensitive strains, which had been localized to regions of the coat gene (Casjens, S., Eppler, K., Sampson, L., Parr, R., and Wyckoff, E. (1991) Genetics 127, 637-647), define 17 sites of single amino acid substitutions by DNA sequencing. Particles assembled from the mutant proteins at permissive temperature were not thermolabile at restrictive temperature, nor defective in the infectious process. At restrictive temperature, ts mutant polypeptide chains were synthesized at near wild-type rates. These inactive chains were not degraded within the cells. The ts chains failed to interact with scaffolding proteins to form the procapsid precursor shell, and they did not polymerize with each to form aberrant shells. Rather, the mutant coat protein accumulated as insoluble aggregates, with the amorphous morphology of inclusion bodies. The results indicate that the chains fail to reach the conformation needed for subunit subunit or subunit-scaffolding interaction. These mutations appear to be of the class of temperature-sensitive folding mutations, which destabilize an intermediate in the intracellular folding pathway. PMID- 8486631 TI - A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes. cDNA cloning and expression of leukotriene B4 omega-hydroxylase. AB - Isolation of cDNA clones for human leukotriene B4 (LTB4) omega-hydroxylase clearly demonstrates that the hydroxylase is a member of the cytochrome P-450 (CYP) superfamily. cDNA clones isolated from a human leukocyte cDNA library with CYP4A4 cDNA as a probe encode a protein of 520 amino acids with a molecular weight of 59,805. The deduced amino acid sequence contains an invariant cysteine in the conserved heme-binding domain near the C terminus, characteristic of the P 450 superfamily. The microsomes from yeast cells transfected with an expression vector pAAH5 carrying isolated cDNA catalyzed the omega-hydroxylation of LTB4 with a Km value of 0.71 microM, and its activity was significantly inhibited by carbon monoxide and by antisera against CYP4A4, consistent with the properties previously reported with LTB4 omega-hydroxylase in human polymorphonuclear leukocytes. The amino acid sequence of LTB4 omega-hydroxylase (P-450LTB omega) shows 31-44% similarity to those of CYP4A, CYP4B, and CYP4C, whereas less than 25% similarity was observed with any of the other P-450 families. According to the systematic classification of the P-450 superfamily, P-450LTB omega is classified into the CYP4 family but does not belong to any of the known CYP4 subfamilies. This P-450 composes a new subfamily of CYP4. RNA blot analysis indicated that mRNA hybridized to the cDNA was expressed in the polymorphonuclear leukocytes as well as leukocytes from four individuals. Isolation of the cDNA opens the way to investigate the physiological role and to regulation of the omega-hydroxylase in the inflammation process. PMID- 8486632 TI - Isolation and characterization of the chains of type V/type XI collagen present in bovine vitreous. AB - Previous studies show that the collagen fibrils of the mammalian vitreous humor are assembled largely from type II collagen with smaller amounts of type IX collagen and either type V or type XI collagen. In this paper, we report the separation of two chains of type V/type XI collagen from type II collagen by heparin-Sepharose chromatography. These chains were characterized by sequencing of selected cyanogen bromide or tryptic peptides with subsequent comparison of these sequences with cDNA-derived amino acid sequences of the alpha 1(V), alpha 1(XI), alpha 2(V), and alpha 2(XI) chains. The results show that vitreous fibrils are assembled from molecules containing the alpha 1(XI) and alpha 2(V) chains. These results, together with recent results from other laboratories, indicate that type V and type XI collagens are not separate collagen types but are part of a larger collagen family in which chains of both type V and type XI collagens participate in the formation of a variety of native molecules. PMID- 8486633 TI - Spermidine-induced destabilization of ornithine decarboxylase (ODC) is mediated by accumulation of antizyme in ODC-overproducing variant cells. AB - The mechanism of spermidine-induced destabilization of ornithine decarboxylase (ODC) was examined in newly isolated ODC-overproducing variant cells by use of an in vitro ODC degrading system. The cells accumulated ODC protein in the presence of alpha-difluoromethylornithine. Addition of spermidine to the medium accelerated degradation of ODC protein concomitantly with induction of antizyme, a regulatory protein that binds to ODC, inhibiting its activity. Both the acceleration of ODC degradation and the induction of antizyme were inhibited by cycloheximide, but not by actinomycin D. ODC was degraded rapidly in extracts from spermidine-treated cells. The rate of ODC degradation correlated with the amount of antizyme in the extracts, and the degradation activity was abolished by treatment of the extracts with anti-antizyme antibody. Thus, antizyme induced by spermidine was essential for the accelerated degradation of ODC in the cells. ODC was phosphorylated in the cells, probably at serine residue 303 in the first internal PEST region. ODC phosphorylation occurred even when its new synthesis was inhibited by cycloheximide. Antizyme accelerated the degradations of both dephosphorylated ODC and native ODC. PMID- 8486634 TI - Characterization of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Mutations on the cytoplasmic surface affect transducin activation. AB - Rhodopsin mutants responsible for autosomal dominant retinitis pigmentosa (ADRP) were prepared by site-directed mutagenesis and characterized. The aim was to evaluate ADRP mutations that occur at three locations on the cytoplasmic surface of rhodopsin: Thr-58 near the cytoplasmic border of helix A, the tetrapeptide Leu 68 to Pro-71 in the first cytoplasmic loop, and Arg-135 at the cytoplasmic border of helix C. It was hypothesized that amino acid changes at these sites would result in mutant rhodopsins with normal spectral properties but defects in their ability to interact with the rod outer segment G protein, transducin. A set of 12 mutant opsin genes was prepared. Four of the mutants were known to cause ADRP: Thr-58 replaced by Arg, a four-amino acid deletion (Leu-68/Arg-69/Thr-70/Pro-71), Arg-135 replaced by Leu, and Arg-135 replaced by Trp. Eight additional mutants were prepared to provide complementary structure-function information. The four amino acid deletion mutant failed to bind 11-cis-retinal. However, each of the Thr-58 and Arg-135 mutants bound 11-cis-retinal to form a pigment with a visible absorbance maximum (lambda max) of 500 nm. Upon illumination, each pigment was converted to a metarhodopsin II-like spectral form (lambda max = 380 nm). However, each of these spectrally normal ADRP mutants was defective in activating guanine nucleotide exchange by transducin. These results identify a defect in the signal transduction pathway in spectrally normal mutant rhodopsins that cause ADRP. PMID- 8486635 TI - Chemotaxis of the marine bacterium Vibrio furnissii to sugars. A potential mechanism for initiating the chitin catabolic cascade. AB - Immense quantities of chitin are catabolized by marine bacteria, and this process involves at least three signal transduction systems in Vibrio furnissii. One system, chemotaxis to chitin oligosaccharides, is probably used to colonize chitin particles. But how do the first few cells find this highly insoluble polysaccharide? The following hypothesis is proposed to answer this question: the bacteria respond to soluble chemo-attractants in exudates from injured organisms. Virtually all chitin-producing organisms also contain glucose and/or trehalose, often at high concentrations such as trehalose in insect hemolymph. Chemotaxis of V. furnissii was therefore studied with a variety of sugars. Fructose, ribose, and glycerol are catabolites but not attractants. The cells exhibit weak constitutive taxis to Glc and GlcNAc. After induction, they show a weak response to galactose but are strongly attracted to the following substrates of the phosphoenolpyruvate:glycose phosphotransferase system (PTS): GlcNAc, trehalose, glucose, sucrose, mannose, and mannitol. There is a rough qualitative but no quantitative correlation between the rate of phosphorylation and the chemotactic response to PTS sugars. Trehalose is especially noteworthy because it is phosphorylated at a very rapid rate by uninduced cells but is not an attractant until the cells are induced. We suggest that unidentified inducible factors link the PTS to chemotaxis. PMID- 8486636 TI - A variant of exotoxin A that forms potent and specific chemically conjugated immunotoxins. AB - To introduce a free sulfhydryl into Pseudomonas aeruginosa exotoxin A (ETA), methionine 161 in domain I of the toxin was changed to cysteine by site-directed mutagenesis. The free sulfhydryl provides a convenient site for covalent attachment of ETA to other proteins in the production of chimeric toxins. The mutation was then introduced into a variant of ETA that is impaired in receptor binding, termed ETA-60EF61, that has the dipeptide Glu-Phe inserted between residues 60 and 61. The resulting double mutant, ETA-60EF61 Cys161, was conjugated to three different monoclonal antibodies via a thioether linkage, and the immunotoxins were tested for cytotoxicity with cells in culture. Each immunotoxin was extremely potent against cells that expressed surface determinants for the monoclonal antibodies but had little cytotoxicity for cells that did not bind the antibodies. For comparison, we also conjugated ricin A chain to each of the three monoclonal antibodies and found that the resulting immunotoxins were at least two-orders of magnitude less potent than the corresponding immunotoxins made with ETA-60EF61Cys161. This study demonstrates that ETA-60EF61Cys161 makes potent and specific immunotoxins and may potentially be useful in selectively eliminating subpopulations of cells in vitro and in vivo. PMID- 8486637 TI - Charged residues render pro-OmpA potential dependent for initiation of membrane translocation. AB - We have examined the effects of positively and negatively charged residues on the translocation of outer membrane protein A precursor (pro-OmpA) across the bacterial inner membrane. Pro-OmpA does not translocate across the membrane when 2 positively charged residues are inserted immediately after the leader peptide, whereas it does insert when 2 neutral or negatively charged residues are introduced. Using a cell-free translocation system, we show that the membrane potential stimulated the rate of initial insertion of pro-OmpA with negatively charged residues, inhibited pro-OmpA with positively charged residues, and had no effect on neutral pro-OmpA. Thus, acidic residues render pro-OmpA potential dependent for loop formation, which then initiates the translocation process. PMID- 8486638 TI - Purification and properties of 2'-hydroxybenzalpyruvate aldolase from a bacterium that degrades naphthalenesulfonates. AB - 2'-Hydroxybenzalpyruvate aldolase catalyzes the cleavage of 2' hydroxybenzalpyruvate to salicylaldehyde and pyruvate. This reaction is part of the degradative pathways for naphthalene and naphthalenesulfonates by bacteria. 2'-Hydroxybenzalpyruvate aldolase has been purified to homogeneity from a bacterium that degrades naphthalenesulfonates (strain BN6). The enzyme has a molecular weight of about 120,000 and is composed of identical subunits with a molecular weight of about 38,500. Thus the enzyme appears to exist as a trimeric oligomer. The NH2-terminal amino acid sequence did not show significant homology to other published amino acid sequences. Extensive loss of enzyme activity occurred when the enzyme was incubated with 2'-hydroxybenzalpyruvate in the presence of sodium borhydride. This suggested the intermediate formation of a stable Schiff base between enzyme and substrate. 2'-Hydroxybenzalpyruvate aldolase was inhibited by p-chloromercuribenzoate and by the reaction product salicylaldehyde. The enzyme converted 2'-hydroxybenzalpyruvate, 2',4'- and 2',6' dihydroxybenzalpyruvate. PMID- 8486639 TI - Expression of dopamine beta-hydroxylase in Drosophila Schneider 2 cells. Evidence for a mechanism of membrane binding other than uncleaved signal peptide. AB - To characterize the mechanism of membrane attachment of dopamine beta hydroxylase, an expression system producing the processed form of this enzyme has been developed. We have replaced the endogenous signal peptide of bovine dopamine beta-hydroxylase with a heterologous signal peptide which is efficiently recognized and cleaved in Drosophila Schneider 2 cells. A cDNA encoding this chimeric recombinant bovine enzyme has been stably transfected into Schneider 2 cells. The inducible expression of active dopamine beta-hydroxylase in these cells has been verified by Western blotting and enzyme activity assays. N terminal sequence analysis of purified recombinant enzyme demonstrates complete removal of the signal peptide. Subcellular analysis shows that the recombinant enzyme exists as both a soluble and a membrane-bound form in these cells. These data demonstrate that the endogenous signal peptide is not required for the formation of the membranous dopamine beta-hydroxylase and further that the enzyme can be bound to membranes via a mechanism other than uncleaved signal sequence. PMID- 8486640 TI - The 5' and 3' untranslated regions of satellite tobacco necrosis virus RNA affect translational efficiency and dependence on a 5' cap structure. AB - Satellite tobacco necrosis virus RNA (STNV RNA) is a naturally uncapped viral RNA that contains 1239 nucleotides: 29 in the 5' untranslated region (UTR), 591 in the coding region and 619 in the 3' UTR. Mutations were made in the 5' and 3' UTRs, and the effects of these mutations on translational efficiency and cap independence were measured in an in vitro translation system from wheat germ. Removal of the first 12 nucleotides or 10 changes in the nucleotide sequence of the 5' UTR reduced translational efficiency approximately 3-fold; capping of these 5' mutant mRNAs restored their translational efficiencies. Truncation of the 3' UTR to nucleotide 627 or 700, or deletion of nucleotides 627-737, reduced translational efficiency more than 20-fold; capping of these 3' mutant mRNAs restored their translational efficiencies. These modifications in the 3' UTR increased the concentration of initiation factor 4F required for translation. Chimeric mRNAs were constructed which contained the coding region of rabbit alpha globin mRNA and either the 5' UTR, 3' UTR, or both the 5' and 3' UTRs of STNV RNA. Both the 5' and 3' UTRs of STNV RNA were necessary to obtain cap-independent translation. These findings indicate that interaction between 5' UTR and the region between nucleotides 627 and 737 in the 3' UTR are required for cap independent translation. PMID- 8486641 TI - Effects of truncation of human pro-tumor necrosis factor transmembrane domain on cellular targeting. AB - Human tumor necrosis factor is initially synthesized as a transmembrane prohormone anchored by a hydrophobic region of the leader sequence. This hydrophobic domain has been previously localized to extend from Leu-46 to Ile-21 based on hydropathy calculations. To functionally determine the nature of this domain, we have generated a series of pro-TNF mutant cDNAs in which either half or both halves of this encoding domain is deleted. These cDNAs were analyzed both by the ability of their mRNAs to direct translation in a microsomal system and by cellular localization of their encoded TNFs following transfection of NIH/3T3 cells. We determined that the mutant protein with deletion of the periluminal region of the transmembrane domain (Thr-32 to Ile-21) was translocated into microsomes and localized on the inner surface of the microsomal membrane in a fashion identical to that of the parental TNF. In contrast, the mutants with deletion of either the pericytoplasmic aspect (Leu-46 to Gly-34) or of virtually the entire transmembrane domain were not localized in the microsomes. Transfection experiments indicated that only the cDNAs whose peptide products were translocated across microsomal membranes gave rise to transmembrane prohormones and matured TNFs. Thus, the functions of membrane targeting and orientation prior to proteolytic processing can be fulfilled by the sequence Leu 46 to Ala-33 of the transmembrane domain, but not by the sequence Ala-33 to Ile 21. PMID- 8486642 TI - Tumor necrosis factor-alpha induces expression of monocyte chemoattractant JE via fos and jun genes in clonal osteoblastic MC3T3-E1 cells. AB - The mechanism by which circulating monocytes are attracted to sites of bone remodeling is unknown. We now report that tumor necrosis factor-alpha (TNF alpha), a potent osteotrophic cytokine, was stimulatory for expression of the monocyte chemoattractant JE gene in osteoblastic MC3T3-E1 cells. TNF-alpha stimulated this JE gene expression transcriptionally. The presence of JE gene product in conditioned medium of the cytokine-treated cells was evidenced by an immunoprecipitation assay with antiserum specific for JE/MCP-1. The stimulated JE gene expression was markedly inhibited by H-7, a potent inhibitor of protein kinase C. Phorbol 12-myristate 13-acetate induced the JE gene expression, and the cytokine-induced JE gene expression was down-regulated by the phorbol ester pretreatment. TNF-alpha induced expression of both early protooncogenes, c-fos and c-jun, in the cells. Antisense oligonucleotides to these oncogenes significantly inhibited the cytokine-induced monocyte chemotactic activity. Furthermore, curcumin, a specific inhibitor of c-jun/AP-1, markedly inhibited JE gene expression and monocyte chemotactic activity induced by the cytokine. These results suggest that TNF-alpha may contribute to the regulation of remodeling and inflammation of bone tissues through the JE gene product. PMID- 8486643 TI - Complex patterns of sequence variation and multiple 5' and 3' ends are found among transcripts of the erythroid ankyrin gene. AB - The structural protein ankyrin functions in red blood cells to link the spectrin based membrane skeleton to the plasma membrane. Ankyrin proteins are now known to occur in most cell types, and two distinct ankyrin genes have been identified (erythroid (Ank-1) and brain (Ank-2)). We have characterized transcripts of the mouse erythroid ankyrin gene by cDNA cloning and DNA sequencing. Ank-1 transcripts of 7.5 and 9.0 kilobases are found in erythroid tissues, and a 9.0 kilobase transcript is found in cerebellum. RNA hybridization blot analysis of 13 additional mouse tissues has detected four novel Ank-1 transcripts (5.0, 3.5, 2.0, and 1.6 kilobases in size). Sequencing of Ank-1 cDNA clones isolated from mouse reticulocyte, spleen, and cerebellar libraries has identified (i) multiple 5' ends that indicate possible multiple promoters; (ii) alternative polyadenylation sites that probably account for the 7.5- and 9.0-kilobase size difference; (iii) a variety of small insertions and deletions that could produce transcripts (and ultimately proteins) of nearly identical size, but different functions; and (iv) clones with large deletions of coding sequence that account for the smaller transcripts seen in spleen, skeletal muscle, and heart. PMID- 8486644 TI - Identification and purification of a novel serine proteinase inhibitor. AB - We report the identification, purification, and partial amino acid sequence of a novel serine proteinase inhibitor which is present in extracts from human placentas and in the cytosolic fraction of the leukemic cell line K562. Extracts from these tissues exhibited time-dependent inhibition of the serine proteinase thrombin. This activity was not accelerated by heparin and corresponded to a protein which formed a 67-kDa complex with 125I-thrombin. The complex was stable on reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A cleaved and functionally inactive form of the protein was purified from placental tissue by chromatography on DEAE-Sepharose, followed by affinity chromatography on thrombin-Sepharose. Antibodies raised against the placental protein recognized the inhibitor from K562 cells and placental extract. Western blotting experiments using the antibody showed that the uncleaved inhibitor has a molecular mass of 38 kDa. Amino acid sequencing was performed on the purified protein. Sequences of peptides resulting from digestion with cyanogen bromide followed by Endoproteinase Lys-c confirmed that this is a novel inhibitor with significant homology to the serpin family. PMID- 8486645 TI - Activation of ADP-ribosylation factor by Golgi membranes. Evidence for a brefeldin A- and protease-sensitive activating factor on Golgi membranes. AB - Recent evidence has implicated ADP-ribosylation factor (ARF) proteins as critical regulators of the protein secretory pathway, particularly in the endoplasmic reticulum-Golgi pathway. We have examined whether Golgi membranes contain activators of ARF and the consequences of ARF activation and acylation on its membrane association. Two means were used to assess ARF activation. First, guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) binding to protein was found to be greater when ARF and Golgi were incubated together than when either was incubated alone. These data suggested that ARF GTP gamma S was formed. This was confirmed by showing that the GTP gamma S-bound protein functioned as a cofactor for cholera toxin-stimulated ADP-ribosylation of Gs alpha, a reaction for which activated ARF is a necessary cofactor. Trypsin treatment of Golgi, an inhibitory ARF peptide, and brefeldin A each inhibited Golgi-mediated activation by approximately 70%, demonstrating that a specific protein interaction is required for the majority of the ARF activation. This ARF-activating protein is a strong candidate for the molecular target for brefeldin A. The ubiquitous nature of ARF proteins and their importance in both the exocytic and endocytic pathways may explain the effects of brefeldin A on both exocytic and endocytic membrane traffic in animal cells. A protease-insensitive activation of ARF by Golgi could also be demonstrated and was the dominant activity observed in submicromolar concentrations of magnesium. We believe this to be the lipid-mediated process described previously for purified ARF proteins. ARF activation resulted in tight association of ARF with phospholipid vesicles. Vesicle association required amino terminal myristoylation of ARF whereas activation did not. These studies indicate that the brefeldin A-sensitive ARF-activating protein and other factors that determine the level of activation of ARF in animal cells are fundamental regulators of membrane traffic in animal cells. PMID- 8486646 TI - Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin). AB - A cDNA clone encoding the human endoplasmic reticulum (ER) resident protein IP90 was isolated and sequenced. It predicts a transmembrane protein with a large ER luminal region showing sequence similarity to calreticulin and a short cytoplasmic domain containing a COOH-terminal RKPRRE sequence that may be relevant to its retention in the ER. It is 95% homologous to the canine ER membrane phosphorprotein called pp90 or calnexin (Wada, I., Rindress, D., Cameron, P. H., Ou, W.-J., Doherty, J. J., II, Louvard, D., Bell, A. W., Dignard, D., Thomas, D. Y., and Bergeron, J. J. M. (1991) J. Biol. Chem. 266, 19599 19610). Previously, in lymphocytes, we have characterized IP90 as a protein associated with partially assembled multichain proteins including the T cell receptor, the membrane immunoglobulin, and the heavy chain of the major histocompatibility complex class I molecules (Hochstenbach, F., David, V., Watkins, S., and Brenner, M. B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4734 4738). Here, we show that within a short metabolic labeling period, IP90 associates transiently with many different newly synthesized proteins. However, in a T cell line that cannot assemble a complete T cell receptor because it lacks the alpha subunit, the unassembled T cell receptor beta chains, which are retained in the ER, remain associated with IP90 throughout a prolonged chase time period. Together, these data offer further evidence suggesting that IP90 may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. PMID- 8486647 TI - Induction of peroxisomal fatty acid beta-oxidation and liver fatty acid-binding protein by peroxisome proliferators. Mediation via the cytochrome P-450IVA1 omega hydroxylase pathway. AB - Both the enzymes of peroxisomal fatty acid beta-oxidation and the liver fatty acid-binding protein (L-FABP) are induced in the liver by peroxisome proliferators, such as clofibrate (CF), as well as high fat diets. One proposed mechanism for this induction is that it represents an adaptive response to altered intracellular fatty acid fluxes, mediated by dicarboxylic fatty acids formed via the cytochrome P-450IVA1 omega-oxidation pathway. The studies presented in this paper were designed to investigate the role of the products of P-450IVA1 omega-oxidation in the regulation of peroxisomal beta-oxidation and L FABP. In primary hepatocyte cultures exposed to CF, the increase in P-450IVA1 activity preceded the induction of peroxisomal beta-oxidation and L-FABP. The CF mediated increases in peroxisomal beta-oxidation and L-FABP, but not P-450IVA1, could be significantly inhibited pretranslationally by concurrent exposure of cultured hepatocytes to inactivators of cytochromes P-450, such as 1 aminobenzotriazole and 10-undecynoic acid. Hexadecanedioic acid, a 16-carbon dicarboxylic fatty acid, that is poorly metabolized in hepatocytes, induced peroxisomal beta-oxidation and L-FABP, but not P-450IVA1, via a pretranslational mechanism that was not inhibited by 1-aminobenzotriazole. Long-chain monocarboxylic acids were without such inducing effect. In further studies, non beta-oxidizable dicarboxylic acid analogs were found to display greater potency as inducers of peroxisomal beta-oxidation when compared to hexadecanedioic acid. The inducing effects of the dicarboxylic acid analogs were also independent of the P-450 omega-oxidation pathway. The results of these studies suggest that the regulation of peroxisomal beta-oxidation enzymes and L-FABP is mediated, to a significant extent, by poorly metabolized long-chain dicarboxylic acids formed via the P-450IVA1 pathway. PMID- 8486648 TI - The calmodulin-binding domain of the mouse 90-kDa heat shock protein. AB - The mouse 90-kDa heat shock protein (HSP90) and Ca(2+)-calmodulin were cross linked at an equimolar ratio using a carbodiimide zero-length cross-linker. To identify the calmodulin-binding domain(s) of HSP90, CNBr-cleaved peptide fragments of HSP90 were mixed with Ca(2+)-calmodulin and cross-linked. Amino acid sequence determination revealed that an HSP90 alpha-derived peptide starting at the 486th amino acid residue was contained in the cross-linked products, which contains a calmodulin-binding motif (from Lys500 to Ile520). A similar motif is present also in HSP90 beta (from Lys491 to Val511). The synthetic peptides corresponding to these putative calmodulin-binding sequences were found to be cross-linked with Ca(2+)-calmodulin and to prevent the cross-linking of HSP90 and Ca(2+)-calmodulin. Both HSP90 alpha and HSP90 beta bind Ca2+. The HSP90 peptides bind HSP90 and thereby inhibit the binding of Ca2+. In addition, the HSP90 peptides augment the self-oligomerization of HSP90 induced at elevated temperatures. These results suggest that the calmodulin-binding domain of HSP90 might interact with another part of the same molecule and that Ca(2+)-calmodulin might modulate the structure and function of HSP90 through abolishing the intramolecular interaction. PMID- 8486649 TI - Identification of a soluble receptor for platelet-derived growth factor in cell conditioned medium and human plasma. AB - We have discovered a soluble form of the platelet-derived growth factor (PDGF) alpha receptor, designated sPDGF-R alpha, that is produced by and secreted into the conditioned medium of the human osteosarcoma cell line, MG-63. Additionally, sPDGF-R alpha activity has been detected in normal human blood plasma and serum. We have achieved partial purification of this protein by column chromatography using three different affinity matrices: anti-PDGF-R alpha monoclonal antibody (mAb) 292.15-Sepharose, PDGF-BB-Sepharose, and wheat germ agglutinin-agarose. All three matrices have been shown to purify a 90-kDa protein that is recognized by mAbs specific for the PDGF-R alpha extracellular domain. sPDGF-R alpha is capable of binding PDGF ligand in solution and can compete with cell-associated PDGF receptors for ligand binding. We provide three pieces of data suggesting that the sPDGF-R alpha is generated by proteolytic clipping of the full-length PDGF-R alpha protein. First, the conditioned medium of an expression cell line transfected with a cDNA construct designed to produce only full-length PDGF-R alpha exhibits sPDGF-R alpha activity. Second, a truncated intracellular fragment of the PDGF-R alpha, presumably representing the intracellular counterpart of the clipped sPDGF-R alpha, can be immunoprecipitated from the MG-63 osteosarcoma cell extracts using antiserum raised against an intracellular portion of PDGF-R alpha. Finally, we have been unable to detect alternative splicing in the PDGF-R alpha transcript using reverse transcription-polymerase chain reaction. PMID- 8486650 TI - Wild type GAL4 binds cooperatively to the GAL1-10 UASG in vitro. AB - Transcription of the genes required for utilization of galactose in Saccharomyces cerevisiae is controlled primarily by the transcriptional activator protein GAL4. The upstream activating sequences for galactose (UASG) of most GAL genes have multiple sites to which GAL4 can bind. In this report we compare the binding properties of wild type GAL4 and derivatives of GAL4 bearing the N-terminal DNA binding domain to multiple DNA-binding sites in vitro. To produce wild type GAL4, we constructed a recombinant baculovirus for expression in insect cells. Recombinant wild type GAL4 was found to bind efficiently to an oligonucleotide containing a near-consensus 17-mer GAL4 DNA-binding site in electrophoretic mobility shift assays. Footprinting experiments revealed that wild type GAL4 binds cooperatively to the four GAL4 DNA-binding sites of the GAL1-10 UASG; however, in contrast an N-terminal fragment of GAL4 containing only the DNA binding/dimerization domains binds to each of these sites with slightly different affinity. With increasing concentrations of GAL4(1-147), the four sites become filled in the following order: site II, site IV, site I, and site III. In experiments with wild type GAL4, these four sites become fully occupied at approximately the same concentration of protein. In footprints of wild type GAL4 on the USAG, enhancements and protections of DNase I-sensitive cleavages are detectable between sites III and IV, indicative of formation of a loop between these distantly spaced sites. Binding of wild type GAL4 to a strong near consensus binding site assists binding to an adjacent mutant site in both electrophoretic mobility shift and footprinting assays. GAL4(1-147) and GAL4(1 147) fused to portions of GAL4's activating region II were incapable of cooperative DNA binding in our assays. We conclude from these observations that wild type GAL4 has a cooperative DNA-binding function that is distinct from the DNA binding and dimerization or transcriptional activation functions, and likely plays and important role in precise regulation of GAL gene transcription. PMID- 8486651 TI - Locations and immunoreactivities of phosphorylation sites on bovine and porcine tau proteins and a PHF-tau fragment. AB - Tau protein is a phosphorylated neuronal microtubule-associated protein. Tau protein is also present in the major pathological lesions of Alzheimer's disease in an insoluble hyperphosphorylated state as paired helical filaments (PHFs). We have investigated the phosphorylation state of control taus and a fragment of PHF tau. Tau samples were digested with protease, separated by reversed-phase high performance liquid chromatography, and analyzed by mass spectrometry and Edman microsequencing. The serine homologous with S404 of human tau 441 was phosphorylated on bovine and porcine tau and up to two phosphates were present on a peptide of amino acids 182-240 of bovine tau (193-251 of human tau 441). The serine within the KSPV motif was not phosphorylated on bovine or porcine tau. PHF tau fragments, isolated from pronase-treated PHFs encompassed a 93-amino acid region within the microtubule binding domain. Enzymatic digestion and mass spectrometric analysis showed no phosphate was present and a second carboxyl terminus was identified at E380. Antibodies T3P and SMI34, which recognize PHF tau and peptides phosphorylated at the sequence KSPV, both reacted with bovine and porcine tau even though the KSPV sequence was not phosphorylated. These data indicate that the 93-amino acid sequence of F5.5 tau from PHFs is not phosphorylated, and the serine equivalent to S404 of human tau is phosphorylated in bovine and porcine tau. Antibodies T3P and SMI34 react with phosphorylated epitopes that are not unique to PHF-tau and that are not necessarily at the KSPV site. PMID- 8486652 TI - Expression and role of c-myc in chondrocytes undergoing endochondral ossification. AB - To analyze the relationship between c-myc gene expression and chondrocyte proliferation and maturation during endochondral ossification, Day 18-19 chick embryo sterna were pulse-labeled with [3H]thymidine, and serial sections were processed for autoradiography and in situ hybridization. Proliferating chondrocytes, located in four distinct areas of the developing sternum, all contained high levels of c-myc transcripts, whereas postmitotic chondrocytes (such as hypertrophic chondrocytes) contained undetectable amounts. These findings were confirmed by Northern blot analysis and by the observation that antisense c-myc oligomer treatment inhibited proliferation in cultured chondrocytes. Constitutive overexpression of c-myc by retroviral vectors in immature chondrocyte cultures (c-myc cultures) maintained the cells in a proliferative state and blocked their maturation into hypertrophic chondrocytes. The lack of maturation in the c-myc cultures was corroborated by analysis of type X collagen gene regulation. Control immature cultures contained strong repressor activity for the type X collagen gene promoter, as revealed by transfection assays; repressor activity was lost upon maturation and activation of type X collagen synthesis. In the c-myc cultures, however, repressor activity persisted. Thus, c-myc participates in the normal changes in proliferation accompanying chondrocyte maturation in vivo and in culture. The decreases in c-myc expression and cell proliferation appear to be required for completion of maturation. PMID- 8486653 TI - Lysosomal accumulation of unesterified cholesterol in model macrophage foam cells. AB - Lysosomal accumulation of unesterified (free) cholesterol, following the phagocytic incorporation of cholesteryl oleate lipid droplets, was quantitatively characterized in a murine J774 macrophage foam cell model. The induction of phagocytic incorporation by the macrophages, using an inverted culture technique, allowed the rapid delivery of large amounts of cholesteryl ester droplets to the lysosomes, leading to the subsequent generation of free cholesterol. The lysosomally generated free cholesterol was differentiated from the membrane cholesterol by a double radiolabeling procedure. Free cholesterol accumulation was quantitated in a population of low density lipid-filled lysosomes prepared by ultracentrifugal isolation of a floating lipid fraction from a homogenate of the cholesteryl ester-loaded cells. About 10% of the total N-acetyl-beta glucosaminidase activity, a lysosomal marker, was recovered in the lipid fraction. Negligible amounts of alkaline phosphodiesterase-1, a plasma membrane marker, or membrane cholesterol were present in this fraction. Electron microscopic and cytochemical analysis of the isolated lipid fraction revealed the presence of lysosomes in the fraction with a diameter ranging from 1.5 to 4 microns. Continued hydrolysis of incorporated cholesteryl ester over a 24-h incubation resulted in approximately 30% of the generated free cholesterol in lipid-filled lysosomes. The accumulation of free cholesterol occurred whether or not the cholesterol esterifying enzyme, acyl-CoA: cholesterol acyltransferase, was inhibited. In addition, substantial amounts of free cholesterol accumulated even in the presence of efficient cholesterol acceptor particles, apolipoprotein high density lipoprotein-phosphatidylcholine complexes which stimulate cholesterol efflux. Also, increased accumulation of free cholesterol in the lipid fraction was observed when cholesteryl ester-loaded cells were treated with the compound U-18666A which blocks the movement of lysosomal cholesterol. The data demonstrate that the phagocytic incorporation and hydrolysis of cholesteryl ester lipid droplets by macrophage foam cells lead to a substantial accumulation of free cholesterol in the lipid-filled lysosomes. This process could result in a build-up of lysosomal free cholesterol in macrophage foam cells during the progression of atherosclerotic plaque. PMID- 8486654 TI - Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family. AB - Macrosialin is a heavily glycosylated transmembrane protein of 87-115 kDa, highly and specifically expressed by mouse tissue macrophages, and to a lesser extent by dendritic cells. We have isolated cDNA clones encoding macrosialin from a thioglycollate-elicited peritoneal macrophage cDNA library by transient expression in COS cells and panning with the anti-macrosialin monoclonal antibody FA/11. A single 1.3-kilobase macrosialin transcript was detected in both untreated and phorbol 12-myristate 13-acetate-stimulated RAW cells. The cDNA sequence predicts a type I integral membrane protein of 326 residues with a heavily glycosylated extracellular domain of 306 residues containing nine potential N-linked glycosylation sites and numerous potential O-linked glycosylation sites. The extracellular domain consists of two distinct regions, separated by an extended 12 residue proline-rich hinge; a membrane-distal mucin like domain of 89 residues containing short peptide repeats and consisting of 44% serine and threonine residues; and a membrane proximal domain of 170 residues, which has significant sequence homology to a family of lysosomal associated glycoproteins known as the lamp-1 group. Macrosialin is the murine homologue of the human macrophage glycoprotein CD68 (72% identity, 80% similarity). Both proteins are preferentially expressed by macrophages and share the same bipartite structure having a mucin-like domain and a domain common to the lamp family. Macrosialin and CD68 are the first examples of a lamp family protein with a restricted cell-type-specific expression. They may have evolved from the lamps to carry out specialized functions in dedicated phagocytic cells. PMID- 8486655 TI - High level expression of mammalian protein farnesyltransferase in a baculovirus system. The purified protein contains zinc. AB - The mammalian enzyme protein farnesyltransferase is a heterodimeric protein that catalyzes the addition of a farnesyl isoprenoid to a cysteine in ras proteins. Since oncogenic forms of ras proteins require the farnesyl group for transforming activity, the structure and mechanism of this enzyme are important to define. However, such studies have been difficult to approach because of the low abundance of the enzyme in mammalian tissues and hence the problems of obtaining large quantities of the protein. We report here the co-expression of the two subunits of protein farnesyltransferase by Sf9 cells infected with a recombinant baculovirus containing the coding sequences of both polypeptides. This results in the production of milligram quantities of enzyme which can be readily purified by conventional chromatographic methods. The individual subunits of the enzyme can also be expressed in the Sf9 cells, but the ability to reconstitute active enzyme from extracts containing individual subunits is quite low. In contrast, the enzyme produced by co-expression of the two subunits is fully active and retains the properties of the mammalian form, including the specificity for the COOH terminal amino acid of substrate proteins and the ability to bind short peptides encompassing the prenylation site of a ras protein. Furthermore, through atomic absorption analysis of the purified protein, we have confirmed the previous tentative assignment of protein farnesyltransferase as a zinc metalloenzyme by demonstrating that it contains an essentially stoichiometric amount of zinc. The ability to produce and purify milligram quantities of protein farnesyltransferase readily will allow detailed mechanistic and structural studies on this enzyme. PMID- 8486656 TI - Cloning, sequencing, distribution, and expression in Escherichia coli of flavin containing monooxygenase 1C1. Evidence for a third gene subfamily in rabbits. AB - Two full-length cDNA clones (2.2 kilobases) encoding a newly recognized form of mammalian flavin-containing monooxygenase (FMO) have been isolated from independent libraries constructed with mRNA from different rabbits. The cDNAs encode a polypeptide of 533 amino acids which contains two putative pyrophosphate binding domains and a hydrophobic carboxyl terminus characteristic of FMOs. This sequence is 52 and 57% identical to sequences of the rabbit "hepatic" and "pulmonary" FMOs, respectively, and 55% identical to the sequence of "liver form 2" published recently by Ozols (Ozols, J. (1991) Arch. Biochem. Biophys. 290, 103 115). cDNA for the new FMO (FMO 1C1) hybridizes with two species of mRNA, one of 2.6 kilobases and one of about 5.4 kilobases, from liver or kidney, but not lung. Guinea pig, hamster, rat, and mouse all express this form of FMO in liver, kidney, and lung. FMO 1C1 has been tentatively characterized following expression in Escherichia coli. It is inactive with methimazole as substrate but highly active with n-octylamine. The temperature lability, responses to ions and detergent, and pH optimum of FMO 1C1 are similar to values reported for hepatic FMO. Sequence comparisons and analysis of rabbit and human genomic DNA indicate that FMO 1C1, as well as the pulmonary and hepatic FMOs, comprise a single gene family made up of distinct gene subfamilies (A, B,C,D, ... N), each appearing to contain a single gene. A nomenclature, based on these interrelationships and following the same designations used for classifying cytochromes P-450, is proposed. PMID- 8486657 TI - Multiple endoglycosidase F activities expressed by Flavobacterium meningosepticum endoglycosidases F2 and F3. Molecular cloning, primary sequence, and enzyme expression. AB - The genes for Flavobacterium meningosepticum Endo (endoglycosidase) F2 and Endo F3 were cloned, and their nucleotide sequences were determined. The deduced amino acid sequences were verified independently to a large extent by direct peptide microsequencing of 66 and 84% of native Endo F2 and Endo F3, respectively. Structurally, the Endo F2 and Endo F3 genes code for a typically long leader sequence of 45 and 39 amino acids, respectively, and, in both cases, a mature protein of 290 amino acids. Comparative structural analysis demonstrated minimum overall homology (15-30%) between Endo F1, Endo F2, and Endo F3, but revealed distinct clusters of identical residues distributed throughout the entire sequence, which represent motifs for binding and hydrolysis of beta 1,4-di-N acetylchitobiosyl linkages in complex carbohydrates. The mobility of native Endo F2 and Endo F3 on SDS-polyacrylamide gel electrophoresis, unlike Endo F1, did not correlate with the molecular weights determined from the coding region of the corresponding genes. Mass spectrometry confirmed that Endo F2 and Endo F3 were heterogeneous and contained approximately 4000 and 1200 daltons of mass not accounted for in the gene structure. We presume that Endo F2 and Endo F3 are variably post-translationally modified during secretion by possible linkage to the hydroxyl of serine. PMID- 8486658 TI - Use of endoproteases to identify catalytic domains, linker regions, and functional interactions in soluble peptidylglycine alpha-amidating monooxygenase. AB - The production of alpha-amidated peptides is accomplished through the sequential action of two enzymes, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), that are contained within the bifunctional peptidylglycine alpha-amidating monooxygenase (PAM) protein. Tissue-specific alternative splicing and endoproteolysis are known to generate both soluble and integral membrane mono- and bifunctional PAM proteins. In order to investigate the functional consequences of these differences we purified PAM-3, a soluble 95-kDa bifunctional form of the enzyme, from the spent medium of stably transfected hEK-293 cells. Using NH2-terminal sequence analysis of products of limited endoproteolysis and antibody cross-reactivity we identified protease-sensitive regions at the NH2 terminus, between the 35-kDa PHM and 42-kDa PAL domains and at the COOH terminus of the protein. Endoproteolytic removal of the COOH-terminal region from the bifunctional PAM-3 protein shifted the pH optimum of PHM to a more alkaline pH, increased the turnover number (kappa(cat)) of PHM and decreased its KM for alpha-N-acetyl-Tyr-Val-Gly; the catalytic properties of PAL were not altered. Since peptide amidation can be a rate-limiting step in the biosynthesis of neuropeptides, similar increases in PHM activity in vivo may play an important role in regulating the extent of peptide alpha-amidation. PMID- 8486659 TI - Molecular analysis of human beta-arrestin-1: cloning, tissue distribution, and regulation of expression. Identification of two isoforms generated by alternative splicing. AB - The cDNA for human beta-arrestin-1 was cloned by polymerase chain reaction (PCR) and identified based on its remarkably high amino acid identity (98.6%) with the bovine sequence. Two alternatively spliced isoforms of human beta-arrestin-1, differing only in the presence or absence of 24 base pairs/8 amino acids within the sequence, were identified and called beta-arrestin-1A and beta-arrestin-1B, respectively. Both isoforms were found in all tissues tested. Southern blot analysis revealed the existence of a single gene for beta-arrestin-1, suggesting that the two isoforms are generated by alternative mRNA splicing. The possible presence of similar isoforms was investigated for the other members of the arrestin/beta-arrestin gene family by PCR. Two isoforms of arrestin were revealed in bovine peripheral blood leukocytes. The expression of beta-arrestin-1 was studied in several human tissues and cell types. High levels of beta-arrestin-1 mRNA and immunoreactivity were found in peripheral blood leukocytes. The possible regulation of the expression of beta-arrestin-1 was also investigated. Our work documents for the first time that the expression of beta-arrestin-1 is modulated by intracellular cAMP. Using two cell types, human endothelial cells and smooth muscle cells, we found that 6-8-h treatments with the cAMP-inducing agents cholera toxin, forskolin, iloprost, and isoproterenol raised beta-arrestin-1 mRNA by 2-4-fold. Forskolin preferentially increased beta-arrestin-1A expression in smooth muscle cells, as assessed by PCR. beta-Arrestin-1 immunoreactivity was 2-3 fold higher in smooth muscle cells exposed to forskolin for 8 h, compared with untreated controls. We conclude that (i) the finding of alternatively spliced isoforms of beta-arrestin-1 and arrestin documents a novel mechanism to generate diversity within the arrestin/beta-arrestin gene family; (ii) the abundant expression of beta-arrestin-1 in peripheral blood leukocytes further supports our previous suggestion of a major role for the beta ARK/beta-arrestin system in regulating receptor-mediated immune functions; (iii) the increased expression of beta-arrestin-1 by cAMP suggests a new mechanism for the regulation of receptor mediated responses. PMID- 8486660 TI - A transgenic mouse model for studying the lineage relationships and differentiation program of type II pneumocytes at various stages of lung development. AB - A pedigree of transgenic mice has been characterized that contains a H2-Kb/LacZ fusion gene that exhibits integration site-dependent expression from the earliest stages of lung development through adulthood. Histochemical and immunocytochemical studies indicate that the LacZ reporter appears throughout the pulmonary endoderm by embryonic day 11 (E11). A proximal-to-distal wave of extinction of transgene expression occurs during E13-14 that parallels the wave of cytodifferentiation of the pulmonary endoderm. By E16, the LacZ reporter is restricted to the distal portion of epithelial tubules and by birth to scattered cells located in alveoli. Crude epithelial cell suspensions were prepared from lungs harvested from E16 and 14 day postnatal transgenic mice, labeled with the fluorescent LacZ substrate fluorescein di-(beta-galactopyranoside), and the LacZ expressing population isolated by fluorescence-activated cell sorting. Electron microscopic, immunocytochemical and histochemical studies of this purified cell population establish that type II pneumocytes are the only cell lineage that support H2-Kb/LacZ expression in the mature postnatal lung. Fluorescence activated cell sorting of E16 lung suspensions yielded a homogeneous population of cells that produced surfactant protein A, that could be maintained in cell culture, and that are likely precursors of adult type II pneumocytes. Together these studies indicate that (i) expression of the transgene in this pedigree of mice provides a marker for describing early differentiation of the pulmonary epithelium; (ii) the transgene may be useful as an enhancer trap to isolate cis acting sequences that regulate gene transcription within this lineage; (iii) the LacZ reporter expression can be used to purify specific embryonic pulmonary epithelial cell populations; and (iv) primary cultures of these embryonic populations represent a potentially useful model system for analyzing the cellular components and signaling pathways necessary to support and complete passage through the type II pneumocyte differentiation program. PMID- 8486661 TI - The three-dimensional structure of the ligand-binding domain of a wild-type bacterial chemotaxis receptor. Structural comparison to the cross-linked mutant forms and conformational changes upon ligand binding. AB - The three-dimensional structures of the ligand-binding domain of the wild-type Salmonella typhimurium aspartate receptor have been determined in the absence (apo) and presence of bound aspartate (complex) and compared to a cross-linked mutant containing a cysteine at position 36 which does not change signaling behavior of the intact receptor. The structures of the wild-type forms were determined in order to assess the effects of cross-linking on the structure and its influence on conformational changes upon ligand binding. As in the case of the cross-linked mutant receptor, the non-cross-linked ligand-binding domain is dimeric and is composed of 4-alpha-helical bundle monomer subunits related by a crystallographic 2-fold axis in the unbound form and by a non-crystallographic axis in the aspartate-bound form. A comparative study between the non-cross linked and cross-linked structures has led to the following observations: 1) The long N-terminal helices of the individual subunits in the cross-linked structures are bent toward each other to accommodate the disulfide bond. 2) The rest of the subunit conformation is very similar to that of the wild-type. 3) The intersubunit angle of the cross-linked apo structure is larger by about 13 degrees when compared to the wild-type apo structure. 4) The nature and magnitude of the aspartate-induced conformational changes in the non-cross-linked wild-type structures are very similar to those of the cross-linked structures. PMID- 8486662 TI - Rapid agonist-mediated phosphorylation of m3-muscarinic receptors revealed by immunoprecipitation. AB - A specific antiserum against the human m3-muscarinic receptor subtype was made by subcloning a variant region of the third intracellular loop of the m3-receptor (Ser345-Leu463) into a bacterial expression plasmid that produced a fusion protein with glutathione S-transferase. In immunoblot studies this anti-serum identified the human m3-receptor expressed in transfected Chinese hamster ovary (CHO) cells (CHO-m3 cells, 1343 fmol/mg protein) as a diffuse band at approximately 97-110 kDa. In vivo labeling of the ATP pool in CHO-m3 cells with [32P]orthophosphate followed by immunoprecipitation of solubilized m3-receptors revealed that the unstimulated receptor existed in a phosphorylated form. Incubation of CHO-m3 cells with the cholinergic agonist carbachol (1 mM) increased the phosphorylated state of the receptor dramatically, primarily at serine. The time course for agonist-dependent phosphorylation was very rapid occurring within seconds of agonist addition and was maintained for at least 30 min. The muscarinic antagonist atropine (10 microM) inhibited agonist-stimulated phosphorylation. Neither forskolin (10 microM) nor the calcium ionophore, ionomycin (1 microM), had any effect on the state of phosphorylation of the m3 receptor, eliminating a role for cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in the agonist-dependent phosphorylation of m3-receptors. 4 beta-Phorbol 12 beta-myristate 13 alpha-acetate (100 nM) did increase m3-receptor phosphorylation, an effect that was inhibited by the selective protein kinase C inhibitor RO-318220 (10 microM). However, agonist stimulated m3-receptor phosphorylation was not inhibited by RO-318220 indicating that protein kinase C was not involved in agonist-induced m3-receptor phosphorylation. In conclusion the phosphorylation of m3-receptors, in vivo, was increased following the application of muscarinic agonist or PMA. The response to agonist was mediated via a kinase distinct from protein kinase C, protein kinase A and Ca2+/calmodulin dependent protein kinase, whereas the effect of 4 beta phorbol 12 beta-myristate 13 alpha-acetate was mediated by protein kinase C. PMID- 8486663 TI - Hormonal/metabolic regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice. AB - To examine the hormonal/metabolic as well as tissue-specific expression of the GLUT4/muscle-fat facilitative glucose transporter gene, we have generated several transgenic mouse lines expressing a human GLUT4 mini-gene which extends 5.3 kilobases (kb) upstream of transcription start and terminates within exon 10. This construct (hGLUT4-11.5) was expressed in a tissue-specific pattern identical to the endogenous mouse GLUT4 gene. The transcription initiation sites of the transgenic construct were similar to the GLUT4 gene expressed in human tissues. To investigate the hormonal/metabolic-dependent regulation of GLUT4, the transgenic animals were made insulin-deficient by streptozotocin (STZ) treatment. In these animals, STZ-induced diabetes resulted in a parallel decrease in endogenous mouse GLUT4 mRNA and the transgenic human GLUT4 mRNA in white adipose tissue, brown adipose tissue, and cardiac muscle. Similarly, insulin treatment of the STZ-diabetic animals restored both the endogenous mouse and transgenic human GLUT4 mRNA levels. To further define cis-regulatory regions responsible for this hormonal/metabolic regulation, the same analysis was performed on transgenic animals which carry 2.4 kb of the human GLUT4 5'-flanking region fused to a CAT reporter gene (hGLUT4[2.4]-CAT). This reporter construct responded similarly to the human GLUT4 mini-gene demonstrating that the element(s) controlling hormonal/metabolic regulation and tissue specificity all reside exclusively within 2.4 kb of the transcriptional initiation site. PMID- 8486664 TI - Microtubule-associated protein 2 alters the dynamic properties of microtubule assembly and disassembly. AB - The influence of microtubule-associated protein 2 (MAP2) on the dynamics of microtubule assembly and disassembly from axonemal fragments was characterized in vitro in solutions of pure tubulin and varying concentrations of MAP2. A mechanistic description of interactions between MAP2 and individual microtubules was developed from analysis of recorded images obtained by video-enhanced differential-interference-contrast light microscopy. MAP2 decreased the rates and lengths of shortening events and decreased the frequency of transitions between growth and shortening over a wide range of concentrations, thereby producing the increases in net microtubule growth previously described by light-scattering techniques. Increases in rates and lengths of elongation phases, as well as rescue frequencies (i.e. transition from shortening to growth), were observed under conditions in which microtubules are expected to be saturated with MAP2. During early stages of nucleated assembly, MAP2 greatly increased the number of microtubules growing from a given axoneme and caused elongation of "curved" structures which may be sheet-like microtubules. PMID- 8486665 TI - Deficient expression of decorin in infantile progeroid patients. AB - Fibroblasts from young patients exhibiting clinical features of progeroidal syndromes showed decreased biosynthesis of the small proteoglycan decorin. Cells in culture were metabolically labeled, and proteoglycans secreted into the medium were analyzed electrophoretically after immunoprecipitation with antibodies raised against decorin and biglycan. Fluorograms showed regularly a reduction to 15-30% of the normal amount of mature decorin and its core protein after chondroitin ABC lyase treatment. The size of the glycosaminoglycan chains was increased, but there was no obvious anomaly in the secretion kinetics of the mature proteoglycan. In addition, the patients' fibroblasts synthesized an increased amount of biglycan compared to control cells from healthy donors. Northern blot analysis clearly demonstrated a reduction by 85-94% in decorin mRNA, but biglycan mRNA was concomitantly increased, indicating that these alterations occur at the transcriptional level of protein expression. Transcription of decorin in fibroblasts from one of the patients was stimulated up to 3-fold by treatment with interleukin-1 beta. No response to interleukin-1 beta and transforming growth factor-beta was observed in the cells from another patient. In situ hybridization of cultured cells with an antisense decorin probe showed that decorin levels were reduced throughout the cell population. Surprisingly, subsequent examination of cells from one of the patients, now in mid-teenage, revealed a return to normal levels of decorin expression compared to age-matched controls. These studies suggest that, as in Marfan's syndrome where the primary defect concerns the fibrillin gene, reduced decorin expression contributes to the formation of an abnormal matrix and the pathogenesis of these disorders. They also indicate that this abnormality is likely to represent a secondary phenomenon which leads to a fault in the regulation of decorin gene transcription. PMID- 8486666 TI - A high affinity conformational state on VLA integrin heterodimers induced by an anti-beta 1 chain monoclonal antibody. AB - The VLA integrin subfamily includes receptors for extracellular matrix proteins as well as receptors involved in cell-cell adhesive interactions. We have previously described the up-regulation of VLA integrin-mediated cell attachment to different ligands by the anti-beta 1 TS2/16 monoclonal antibody (mAb) (Arroyo, A. G., Sanchez-Mateos, P., Campanero, M. R., Martin-Padura, I., Dejana, E., and Sanchez-Madrid, F. (1992) J. Cell Biol. 117, 659-670). In this report, we have investigated the mechanism involved in this regulatory effect. The anti-beta 1 mediated regulatory effect on cell adhesion did not require "de novo" protein synthesis, since it was not affected by pretreatment with either cycloheximide or actinomycin D. To quantitate the effect of the regulatory anti-beta 1 TS2/16 mAb on the affinity of VLA-5 for its ligand, an RGD-containing fragment of fibronectin (FN80), we performed binding studies of radiolabeled soluble FN80 to U-937 cells. The affinity of VLA-5 for FN80 was enhanced about 4-fold in the presence of TS2/16 mAb (Kd = 0.98 +/- 0.07 microM) compared to the functionally irrelevant anti-beta 1 Alex 1/4 mAb (Kd = 4.23 +/- 0.92 microM), whereas no alteration in the number of binding sites was observed. Indeed, the anti-beta 1 TS2/16 mAb is inducing this high affinity state on VLA heterodimers by a direct change on the conformation of these receptors as demonstrated by affinity chromatography analysis using extracellular matrix proteins covalently bound to Sepharose. The yield of VLA-5 fibronectin receptor bound to FN80-Sepharose columns was strongly increased upon treatment of U-937 cell lysates with mAb TS2/16. Moreover, higher concentrations of EDTA were required for eluting the VLA 5 integrin from this matrix. This up-regulatory effect was also observed with F(ab')2 and Fab fragments of the anti-beta 1 TS2/16 mAb, and was also exerted on the purified VLA-5 receptor. Similarly, the yield of VLA-2 retained on a collagen I-Sepharose column was dramatically increased by pretreatment of A375 melanoma cell lysates with the mAb TS2/16. Altogether, these results indicate that the interaction of VLA beta 1 heterodimers with their ligands can be regulated by switching between differently active conformations inherent to the alpha beta 1 receptors. PMID- 8486668 TI - Enzymatic characterization of beta-D-galactoside alpha 2,3-trans-sialidase from Trypanosoma cruzi. AB - The substrate specificity, physico-chemical, and kinetic properties of the trans sialidase from Trypanosoma cruzi have been investigated. The enzyme demonstrates activity towards a wide range of saccharide, glycolipid, and glycoprotein acceptors which terminate with a beta-linked galactose residue, and synthesizes exclusively an alpha 2-3 sialosidic linkage. Oligosaccharides which terminate in Gal beta 1-4(Fuc alpha 1-3)GlcNAc, Gal beta 1-3(Fuc alpha 1-4)GlcNAc, or Gal alpha 1- are not acceptor-substrates. The enzyme utilizes alpha 2,3-linked sialic acid when the donor species is an oligosaccharide and can also transfer, at a low rate, sialic acid from synthetic alpha-sialosides such as p-nitrophenyl-alpha-N acetylneuraminic acid, but NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)Glc is not a donor-substrate. The trans-sialidase has an apparent pH optimum of 7.9 and a temperature optimum of 13 degrees C. The kinetic properties of the enzyme suggest that the trans-sialylation reaction may occur via a rapid equilibrium random or steady-state ordered mechanism. A method for immobilizing the enzyme is described together with examples of its use for the synthesis of oligosaccharide and glycoprotein precursors of sialyl-Lewis and sialyl-Lewis. PMID- 8486667 TI - Neural expression of a novel alternatively spliced and polyadenylated Gs alpha transcript. AB - We have isolated an alternative transcript of the rat Gs alpha signal transduction protein gene, referred to as Gs alpha N1. Gs alpha N1 was isolated by differential hybridization screening of genes induced upon dexamethasone treatment of the neuronal-like CA77 rat thyroid C-cell line. The 1-kilobase Gs alpha N1 transcript is generated by alternative splicing and polyadenylation of a novel terminal exon. This exon lies 800 base pairs downstream of exon 3 in the Gs alpha gene. Dexamethasone differentially induced Gs alpha N1 severalfold relative to Gs alpha mRNA in the CA77 cells, similar to the bias seen with alternative processing of the calcitonin/calcitonin gene-related peptide transcript. In addition to the differential regulation by dexamethasone, the expression pattern of Gs alpha N1 in rat tissues differed markedly from Gs alpha. Gs alpha N1 mRNA was much more abundant in the brain, with intermediate levels in skeletal muscle and very low levels in other tissues. This was in contrast to the more ubiquitously expressed Gs alpha mRNA. Within the brain, Gs alpha N1 was particularly abundant in discrete regions of the brainstem and hypothalamus that modulate autonomic functions. Examination of rat embryos demonstrated that Gs alpha is expressed in both brain and nonneural tissue at least 1 day before Gs alpha N1 mRNA could be detected in the embryonic brain. Based on the regulated expression of the Gs alpha N1 transcript and previous studies on G alpha proteins, the predicted Gs alpha N1 protein may potentially modulate several heterotrimeric G protein functions in the nervous system. PMID- 8486669 TI - The specific association of a phosphofructokinase isoform with myocardial calcium independent phospholipase A2. Implications for the coordinated regulation of phospholipolysis and glycolysis. AB - We have demonstrated previously that myocardial cytosolic calcium-independent phospholipase A2 is a 40-kDa polypeptide regulated by ligand-modulated protein protein interactions (Hazen, S.L., and Gross, R.W. (1991) J. Biol. Chem. 266, 14526-14534). We now demonstrate that an 85-kDa polypeptide which possesses sequence homology to and chemical, physical, immunological, and chromatographic similarities with phosphofructokinase (PFK) specifically interacts with the 40 kDa phospholipase A2 catalytic subunit and represents the putative protein regulatory element identified in previous work. Multiple independent lines of evidence document the association between the 85-kDa phosphofructokinase isoform and the 40-kDa myocardial cytosolic calcium-independent phospholipase A2 catalytic polypeptide, including 1) the coelution of the 85- and 40-kDa polypeptides which migrate as a 400-kDa complex during gel filtration chromatography, 2) the stoichiometry between the 85- and 40-kDa polypeptides which corresponds to a complex comprised of a tetrameric PFK isoform and a 40-kDa phospholipase A2 catalytic polypeptide, 3) the demonstration that the 85-kDa phosphofructokinase isoform acts as a specific and reversible affinity adsorbent for myocardial cytosolic phospholipase A2 catalytic activity, 4) the immunoprecipitation of myocardial cytosolic phospholipase A2 activity utilizing chicken anti-rabbit skeletal muscle PFK IgG, 5) the specific release of phospholipase A2 from ATP-agarose after formation of a ternary complex comprised of allosteric modifiers of phosphofructokinase, and 6) the selective attenuation of the denaturation of purified homogeneous calcium-independent cytosolic phospholipase A2 with PFK. Collectively, these results demonstrate the highly specific association of a phosphofructokinase isoform with myocardial cytosolic calcium-independent phospholipase A2 and suggest a novel biochemical mechanism underlying the coordinated regulation of phospholipolysis and glycolysis previously observed in myocardium and in other mammalian tissues. PMID- 8486670 TI - Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption. AB - We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express beta 1 and beta 3 integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by alpha v beta 3, while a beta 1 integrin is responsible for attachment to fibronectin. Both the rapid attachment by osteoclasts to intact bone particles and their subsequent resorption are blocked by a monoclonal antibody directed to the alpha v beta 3 complex but not by an antibody against beta 1 integrins. Attachment of osteoclasts to bone is also inhibited with soluble osteopontin, Arg-Gly-Asp-containing peptides derived from both osteopontin and bone sialoprotein, or a monospecific polyclonal antibody against osteopontin. We conclude that both osteoclast adherence to bone and subsequent resorption of its matrix are dependent on interactions between the bone matrix proteins osteopontin and/or bone sialoprotein and the integrin alpha v beta 3. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone. PMID- 8486671 TI - Characterization of endomannosidase inhibitors and evaluation of their effect on N-linked oligosaccharide processing during glycoprotein biosynthesis. AB - Endo-alpha-D-mannosidase is a Golgi-located processing enzyme that achieves deglucosylation of N-linked carbohydrate units through its unique property of cleaving the oligosaccharide chain internally with the release of glucose substituted mannose (Glc1-3Man). By chemically modifying the characteristic disaccharide product, Glc alpha 1-->3Man, a number of potent inhibitors of the endomannosidase were obtained, foremost among which were Glc alpha 1-->3(1 deoxy)mannojirimycin (Glc alpha 1-->3DMJ) and Glc alpha 1-->3(1,2-dideoxy)mannose (IC50 = 1.7 and 3.8 microM, respectively), which, while blocking the in vitro action of the enzyme, had negligible effect on other endoplasmic reticulum- and Golgi-processing glycosidases. Although preparation of a large number of Glc alpha 1-->3DMJ derivatives did not yield a more effective endomannosidase inhibitor it provided valuable information relating to the structural requirements for the enzyme-substrate interaction. Glc alpha 1-->3DMJ was found to be active not only on rat liver endomannosidase but also on the enzyme from a number of other sources including mouse lymphoma (BW5147.3), HepG2, baby hamster kidney, and Madin-Darby canine kidney cell lines. When tested in vivo in lymphoma and Madin-Darby canine kidney cells during a castanospermine-imposed glucosidase blockade, Glc alpha 1-->3DMJ interrupted the endomannosidase processing pathway as evident from a concomitant inhibition of complex oligosaccharide formation and Glc3Man release; similarly the capacity of the glucosidase II-deficient mouse lymphoma cell line (PHAR2.7) to synthesize complex oligosaccharides was blocked by Glc alpha 1-->3DMJ. Endomannosidase could not be detected in Chinese hamster ovary cells by in vitro assay and consistent with this these cells produced only glucosylated polymannose N-linked oligosaccharides during glucosidase blockade. It would appear that by acting in conjunction with a glucosidase inhibitor, Glc alpha 1-->3DMJ and related endomannosidase-blocking agents could have the potential of influencing the exit of glycoproteins from the endoplasmic reticulum and interfering with viral replication. PMID- 8486672 TI - Role of calcium entry and protein kinase C in the progression activity of insulin like growth factor-I in Balb/c 3T3 cells. AB - We previously reported that insulin-like growth factor-I (IGF-I) stimulated calcium entry (Kojima, I., Matsunaga, H., Kurokawa, K., Ogata, E., and Nishimoto, I. (1988) J. Biol. Chem. 263, 16561-16567) and production of 1,2-diacylglycerol in IGF-responsive "primed competent" Balb/c 3T3 cells (Kojima, I., Kitaoka, M., and Ogata, E. (1990) J. Biol. Chem. 265, 16846-16850). The present study was conducted to determine a role of protein kinase C (PKC) in the progression activity of IGF-I. To monitor the activity of PKC in intact cells, we measured phosphorylation of a synthetic KRTLRR peptide, a substrate of PKC, immediately after the permeabilization of the cells with digitonin. When 1 nM IGF-I was added to primed competent cells, KRTLRR peptide phosphorylation was augmented. IGF-I induced more than 2-fold increase in KRTLRR peptide phosphorylation that was blocked by PKC19-36, a pseudosubstrate of PKC, which blocks the activity of the kinase, and Ro31-8220, an inhibitor of PKC. The phosphorylation remained elevated for up to 6 h. To assess the role of PKC in cell cycle progression, IGF-I-induced nuclear labeling was measured in the presence of Ro31-8220. Ro31-8220 reduced the rate of entrance into S phase when added in the first quarter of the G1 phase, but did not affect cell cycle progression when added at the second quarter or later. In contrast, reduction of extracellular calcium completely blocked cell cycle progression when done in the first, second, and third quarter but had no effect in the last quarter. These results indicate that IGF-I persistently activates PKC in primed competent cells, but the activation is required only for the initiation of progression. We conclude that IGF-I promotes cell cycle progression by calcium-dependent mechanisms that are largely independent of PKC. PMID- 8486673 TI - Studies on the carbohydrate moiety and on the biosynthesis of rat C-reactive protein. AB - Rat C-reactive protein (CRP) is a pentameric glycoprotein composed of five apparently identical monomers, two of which form a disulfide-linked dimer (Rasosouli, M., Sambasivam, H., Azadi, P., Dell, A., Morris, H. R., Nagpurkar, A., Mookerjea, S., and Murray, R. K. (1992) J. Biol. Chem. 267, 2947-2954). In this study, the nature of the oligosaccharide chain of rat CRP was investigated by fast atom bombardment-mass spectrometry (FAB-MS), and general features of its biosynthetic pathway were also analyzed. FAB-MS, electrospray-mass spectrometry, and linkage analysis demonstrated that each monomer of rat CRP contained one oligosaccharide chain, predominantly a disialylated biantennary structure, attached to Asn-128. The biosynthesis of rat CRP was studied by immunoprecipitation of CRP synthesized in vitro and by cultured hepatocytes. The results revealed that each monomer of rat CRP was synthesized individually as a single-chain precursor with a cleavable signal sequence. The translocated species was sensitive to digestion by endoglycosidase H (endo H), indicating that it possessed a high mannose oligosaccharide. Rat CRP acquired the ability to bind to phosphorylcholine-Sepharose and to form the dimeric and oligomeric species prior to acquiring resistance to endo H. Studies using tunicamycin revealed that the N linked oligosaccharide present in rat CRP was not required for formation of its dimeric component, oligomerization, ability to bind to phosphorylcholine, or secretion. The non-glycosylated rat CRP, however, was still able to bind to phosphorylcholine-Sepharose and to be secreted by hepatocytes. PMID- 8486674 TI - The specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase as inferred from a database of in vivo substrates and from the in vitro glycosylation of proteins and peptides. AB - The acceptor substrate specificity of UDP-GalNAc:polypeptide N acetylgalactosaminyltransferase (GalNAc-transferase) was inferred from the amino acid sequences surrounding 196 O-glycosylation sites extracted from the National Biomedical Research Foundation Protein Database. When analyzed according to the cumulative enzyme specificity model (Poorman, R.A., Tomasselli, A.G., Heinrikson, R.L., and Kezdy, F.J. (1991) J. Biol. Chem. 266, 14554-14561) these data were found to be consistent with an enzymatic active site which interacts with an 8 amino-acid long segment of the substrate, spanning 3 amino acid residues preceding and 4 amino acid residues following the reactive serine or threonine. The model postulates independent interactions of the 8 amino acid moieties with their respective binding sites, designated as subsites P3 through P0 and P1' to P4'. High selectivity is expressed at all subsites toward serine, threonine, and proline. The inferred specificity was confirmed by in vitro bovine colostrum GalNAc-transferase-catalyzed glycosylation of unglycosylated proteins containing predicted sites for O-glycosylation and synthetic peptides designed to be GalNAc acceptors. In synthetic peptides the bovine colostrum GalNAc-transferase glycosylates threonine about 35 times faster than serine. Our results suggest that the specificity of the enzyme is not dependent on any particular secondary structure of the substrate but, rather, it is determined by the amino acids in the acceptor peptide segment as well as by the accessibility of this segment. It also appears likely that bovine colostrum GalNAc-transferase is able to catalyze in vivo the glycosylation of both threonine and serine residues. PMID- 8486675 TI - Kinetics of binding and hydrolysis of a series of nucleoside triphosphates by actomyosin-S1. Relationship between solution rate constants and properties of muscle fibers. AB - We have measured the steady state kinetics of hydrolysis and presteady state kinetics of binding of the nucleoside triphosphate GTP, CTP, aza-ATP (1-N6-etheno 2-aza-ATP), and ATP by rabbit skeletal actomyosin-S1. The maximum rates of steady state hydrolysis at 10 degrees C at low ionic strength are: CTP, 1.9 s-1 > ATP, 1.3 s-1 > aza-ATP, 0.19 s-1 > GTP, 0.03 s-1. A similar dependence of the rate of steady state hydrolysis upon nucleotide structure has been observed in isometrically contracting muscle fibers in the accompanying paper (Pate, E., Franks-Skiba, K., White, H., and Cooke, R. (1993) J. Biol. Chem. 268, 10046 10053) which strongly suggests that the same biochemical step that limits the maximum rate of hydrolysis of nucleoside triphosphates by actomyosin-S1 in solution also limits the rate of hydrolysis by isometrically contracting muscle fibers. The apparent second order rate constants for the dissociation of actomyosin-S1 by nucleoside triphosphates at 10 degrees C are: ATP, 2.7 x 10(6) M 1 s-1 > aza-ATP, 3.4 x 10(5) M-1 s-1 > GTP, 2.5 x 10(5) M-1 s-1 > CTP, 1.4 x 10(5) M-1 s-1. There is an excellent correlation between the second order rate constant for the dissociation of actomyosin-S1 in solution and the dependence of shortening velocity in glycerinated muscle fibers upon the concentration for ATP, aza-ATP, and CTP (as per accompanying article; Pate et al., 1993). We have used the second order rate constants obtained in solution for the dissociation of actomyosin-S1 by these nucleotides and shortening velocity data obtained with the same nucleoside triphosphates in glycerinated psoas fibers in the accompanying article (Pate et al., 1993) to determine the average distance over which cross bridges remain attached during unloaded shortening to be 5-12 nm. PMID- 8486676 TI - The use of differing nucleotides to investigate cross-bridge kinetics. AB - We have investigated the ability of the nucleotides GTP, CTP, and 1-N6-etheno-2 aza-ATP (aza-ATP) to support contraction of chemically skinned rabbit psoas fibers. Working at 10 degrees C, millimolar concentrations of all nucleotides relaxed fibers in the absence of calcium. In active fibers, GTP served as a very poor substrate with isometric tension, isometric GTPase rate, and maximum shortening velocity (Vmax) all less than 10% of those obtained with ATP. Aza-ATP was only a slightly better substrate. CTP, on the other hand, was an effective substrate with mechanical parameters which were 65-100% those obtained with ATP, and with a hydrolysis rate that exceeded that of ATP. For all three ligands, Vmax followed Michaelis-Menten saturation behavior with values for Km which were from 2.5 to 12 times greater than that for ATP, showing that the analogs bound slowly to myosin in the fibers. Increasing concentrations of orthophosphate inhibited tension with CTP, to a lesser extent with aza-ATP, but not all with GTP. A combination of the mechanical data obtained in fibers with the kinetic data obtained in solution (White, H.D., Belknap, B., and Jiang, W. (1993) J. Biol. Chem. 268, 10039-10045) is used to better define the actomyosin interaction in fibers. PMID- 8486677 TI - 5-Lipoxygenase metabolites of arachidonic acid stimulate isolated osteoclasts to resorb calcified matrices. AB - Bone resorption requires cooperation between osteoclasts and mononuclear accessory cells by mechanisms which have not been elucidated. Since multinucleated cells in giant cell tumors of bone have many phenotypic and functional characteristics of normal osteoclasts, we have examined the interaction between the bone-resorbing multinucleated cells and the distinct mononuclear stromal cells from these tumors. We have found that these mononuclear cells produce an activity which stimulates both giant cells from giant cell tumors and rodent osteoclasts to resorb bone in vitro. We have identified the activity and found that it represents several products of the 5-lipoxygenase pathway of arachidonic acid metabolism, namely 5-hydroxyeicosatetraenoic acid and the leukotrienes. These data indicate that 5-lipoxygenase metabolites stimulate isolated osteoclasts to resorb bone in vitro and may represent a mechanism by which mononuclear stromal cells in human giant cell tumors communicate with the giant cells. In addition, these results may explain a possible mechanism for communication between accessory cells and osteoclasts involved in normal bone resorption. PMID- 8486678 TI - Simultaneous incorporations of two anticancer drugs into DNA. The structures of formaldehyde-cross-linked adducts of daunorubicin-d(CG(araC)GCG) and doxorubicin d(CA(araC)GTG) complexes at high resolution. AB - Anthracycline antibiotics (notably daunorubicin (DAU) and doxorubicin (DOX)) and nucleoside analog arabinosylcytosine (araC or aC) are important anticancer drugs. They are sometimes used together in the treatment of certain cancers. Both classes of compounds act by blocking DNA replication and transcription. To probe whether both drugs can be incorporated simultaneously into DNA and the possible structural consequences, we carried out x-ray diffraction analyses of the complexes between DAU/DOX and araC-containing DNA hexamers cross-linked with formaldehyde. The crystal structures were determined to high resolution (DAU CGaCGCG, 1.2 A, space group P4(1)2(1)2, R = 0.182, 3275 reflections; DOX-CAaCGTG, 1.5 A, space group C2, R = 0.175, 3359 reflections), and they are similar to those of the previously studied DAU- and DOX-DNA complexes, despite different crystal packings. Two DAU/DOX molecules intercalate at both ends of the helix with their amino sugars in the minor groove. As in the structure of DAU-CGCGCG (Wang, A.H.-J., Gao, Y.-G., Liaw, Y.-C., and Li, Y.K. (1991) Biochemistry 30, 3812-3815), a covalent methylene bridge (from formaldehyde) between the N3' of daunosamine and the N2 of the guanine is formed in both adducts. In DOX-CAaCGTG, the two halves are slightly different with a root-mean-square deviation of 0.322 A between them. The O14 hydroxyls of the intercalated DOXs are within hydrogen bond distances to the O2P atoms of the A2p(aC3) and A8p(AC9) steps. The O2' hydroxyl group from araC does not affect the binding of DAU-DOX or the conformation of the drug-DNA complexes. The results suggest that three major drug modifications on DNA, i.e., intercalation, covalent bond formation, and nucleoside analog incorporation, can coexist in the same DNA molecule without difficulty. When they occur in close proximity in DNA, they may provide an additive inhibitory effect for the target enzymes. PMID- 8486679 TI - Studies of 5-fluorodeoxyuridine 5'-monophosphate binding to carboxypeptidase A inactivated thymidylate synthase from Lactobacillus casei. AB - The binding of 5-fluorodeoxyuridylate (FdUMP) to carboxypeptidase-inactivated thymidylate synthase obtained from methotrexate-resistant Lactobacillus casei was investigated using [3H]FdUMP in a trichloroacetic acid precipitation assay and by 19F nuclear magnetic resonance spectroscopy. The cleavage of 1 valine residue from the carboxyl terminus of one of the identical subunits of the enzyme dimer correlates with complete loss of thymidylate synthesis (Aull, J. L., Loeble, R. B., and Dunlap, R. B. (1974) J. Biol. Chem. 249, 1167-1172). We have further investigated the phenomenon of carboxypeptidase A-dependent inactivation of thymidylate synthase by employing immobilized carboxypeptidase A in order to facilitate the isolation and characterization of the inactivated enzyme. The time course of carboxypeptidase treatment of thymidylate synthase has been profiled by the spectrophotometric assay, tritium release assay, trichloroacetic acid precipitation assay (covalent adduct analysis), 19F nuclear magnetic resonance spectroscopy, and amino acid analysis. The techniques utilized in this study yielded results which showed that the completely inactivated enzyme (failure to catalyze thymidylate formation) continued to catalyze both covalent FdUMP-enzyme interactions and the formation of the covalent inhibitory ternary complex with the cofactor, 5,1O-methylenetetrahydrofolate, although to a reduced extent, thus effectively uncoupling these processes from thymidylate synthesis activity. PMID- 8486680 TI - Formation of dolichol from dehydrodolichol is catalyzed by NADPH-dependent reductase localized in microsomes of rat liver. AB - The alpha-saturation reaction involved in the biosynthesis of dolichol has been investigated with rat liver preparations. Under improved in vitro conditions with 10,000 x g supernatant of rat liver homogenates in the presence of NADPH at pH 8.0, dolichol was synthesized from isopentenyl diphosphate and Z,E,E geranylgeranyl diphosphate. Neither dolichyl diphosphate nor dolichyl phosphate was detected. The chain length distribution of the dolicohol was the same as that of dehydrodolichyl products. In an assay system containing dehydrodolichol, dehydrodolichyl phosphate, or dehydrodolichyl diphosphate as a substrate, dehydrodolichol was predominantly converted into dolichol. The enzyme that catalyzes the conversion of dehydrodolichol to dolichol was localized in microsomes. The reductase activity was stimulated 9-fold by the addition of a 100,000 x g soluble fraction. The reductase had an opimal pH at 8.0. These results indicate that dolichol is formed from dehydrodolichol in rat liver microsomes. The formation of dolichol from dehydrodolichol was also catalyzed by 10,000 x g supernatant of rat or pig testis homogenates. PMID- 8486681 TI - The functional importance of hydrophobicity of the tyrosine at position 13 of human epidermal growth factor in receptor binding. AB - The tyrosine at position 13 of epidermal growth factor (EGF) has been implicated as playing a role in receptor binding due to its close proximity to the critical arginine 41 residue as well as its high degree of conservation in EGF and EGF like proteins that can bind to the EGF receptor. Site-directed mutagenesis of tyrosine 13 in human EGF (hEGF) was employed to examine the role of this residue in ligand-receptor interaction. The removal of the hydroxyl moiety of the tyrosine by substitution with phenylalanine had little effect on the binding, indicating that it is not involved in any crucial hydrogen bonds with either the receptor or with other regions of the EGF molecule. The substitution of the aromatic tyrosine side-chain with the nonpolar leucine side-chain caused the receptor affinity to decrease only slightly, indicating that aromaticity of the amino acid at this site is also not critical. Substitutions with other hydrophobic residues, isoleucine, valine, and alanine, resulted in a significant decrease in receptor affinity as a function of decreasing hydrophobicity. Substitution of tyrosine 13 with the polar residues histidine and arginine markedly decreased receptor binding affinity, and complete removal of the side chain by substitution with glycine dramatically lowered the binding affinity to 0.3% as compared to wild type. Analysis of three hEGF mutants, Tyr13-->Leu, Tyr13 ->Arg, and Tyr13-->Gly, by circular dichroism showed that the major structural features of hEGF were not significantly altered. The results demonstrate that the decreased receptor affinities of these hEGF mutants are due to disruption of the functional contribution(s) of the tyrosine 13 residue rather than alteration(s) in the overall structural integrity. Overall, the results suggest that the tyrosine 13 side-chain plays a critical role in receptor binding by contributing to hydrophobic receptor-ligand interactions. PMID- 8486682 TI - Purification and characterization of a bovine serum lectin (CL-43) with structural homology to conglutinin and SP-D and carbohydrate specificity similar to mannan-binding protein. AB - A previously undescribed bovine serum lectin (designated CL-43) was identified by its Ca(2+)-dependent binding to mannan and by its molecular mass of 43 kDa under reducing conditions on SDS-PAGE. The lectin was isolated by polyethylene glycol precipitation, affinity chromatography on mannan-Sepharose (followed by elution with EDTA), and absorption on Sepharose-4B-coupled rabbit anti-bovine Ig (to remove anti-mannan antibodies). Fractions containing the lectin were reapplied to mannan-Sepharose. Bound conglutinin was eluted with GlcNAc, and then the 43-kDa lectin, together with mannan-binding protein (MBP), was eluted with mannose. The 43-kDa lectin was separated from MBP by ion exchange chromatography on Mono-Q. On SDS-PAGE under nonreducing conditions the lectin showed a molecular mass of 120 kDa. On gel chromatography under nondissociating conditions the protein was eluted at a volume corresponding to a molecular mass of approximately 750 kDa. Amino acid analysis showed the presence of hydroxyproline and hydroxylysine and a high content of glycine (24.3%) indicating the presence of a collagen-like structure. This was supported by the susceptibility of the protein to collagenase digestion. The designation CL-43 was chosen since this molecule appears to belong to the collectins, i.e. proteins with collagen structure and lectin activity. The N-terminal sequence (27 amino acids) showed 56% identity with bovine SP-D and 44% identity to bovine conglutinin. An inhibition assay with biotinylated CL-43, using solid-phase mannan as ligand, revealed the following carbohydrate inhibition pattern: mannose and ManNAc > fucose > GlcNAc > glucose and maltose > galactose > lactose >> GalNAc. We conclude that CL-43 is a circulating lectin, with structural similarities to bovine conglutinin and SP-D, and a ligand binding profile resembling that of MBP. PMID- 8486683 TI - X-ray crystal structure of a pea lectin-trimannoside complex at 2.6 A resolution. AB - The x-ray crystal structure of pea lectin, in complex with a methyl glycoside of the N-linked-type oligosaccharide trimannosyl core, methyl 3,6-di-O-(alpha-D mannopyranosyl)-alpha-D-mannopyranoside, has been solved by molecular replacement and refined at 2.6-A resolution. The R factor is 0.183 for all data in the 8.0 to 2.6 A resolution range with an average atomic temperature factor of 26.1 A2. Strong electron density for a single mannose residue is found in the monosaccharide-binding site suggesting that the trisaccharide binds primarily through one of the terminal alpha-linked mannose residues. The complex is stabilized by hydrogen bonds involving the protein residues Asp-81, Gly-99, Asn 125, Ala-217, and Glu-218, and the carbohydrate oxygen atoms O3, O4, O5, and O6. In addition, the carbohydrate makes van der Waals contacts with the protein, involving Phe-123 in particular. These interactions are very similar to those found in the monosaccharide complexes with concanavalin A and isolectin 1 of Lathyrus ochrus, confirming the structural relatedness of this family of proteins. Comparison of the pea lectin complex with the unliganded pea lectin and concanavalin A structures indicates differences in the conformation and water structure of the unliganded binding sites of these two proteins. Furthermore, a correlation between the position of the carbohydrate oxygen atoms in the complex and the bound water molecules in the unliganded binding sites is found. Binding of the trimannose core through a single terminal monosaccharide residue strongly argues that an additional fucose-binding site is responsible for the high affinity pea lectin-oligosaccharide interactions. PMID- 8486684 TI - Specific interactions of chemoattractant factor receptors with G-proteins. AB - Stimulation of leukocytes with chemoattractant ligands activates phospholipid turnover and calcium release, ultimately leading to chemotaxis, degranulation, and the inflammatory response. The leukocyte response to these ligands is transduced by the interaction of transmembrane receptors with GTP-binding regulatory proteins (G-proteins). To examine the mechanisms of signal transduction by these receptors, we transfected cDNA clones encoding the receptors for the active cleavage product of the fifth component of complement (C5a) and platelet-activating factor (PAF) into COS-7 cells, then measured the production of inositol phosphates (IP) in response to stimulation with these chemoattractant ligands. Cells transfected with the C5a receptor showed no increase in IP production when stimulated with ligand (5-120 nM). However, in cells co-transfected with these receptors and with the cDNA for G alpha 16, a G protein alpha subunit that is specific to cells of hematopoietic lineage, addition of ligand caused up to a 5-fold increase in IP production. This interaction was specific, as co-transfection of receptors with the G-proteins G alpha q or G alpha 11 did not allow ligand-dependent increase in IP production. In contrast, ligand-dependent activation of IP production was seen in COS cells transfected solely with the PAF receptor. These results indicate that the C5a receptor utilizes signaling pathways distinct from the PAF receptor and suggest that a pertussis toxin-resistant G-protein, G alpha 16, may play a role in the leukocyte response to inflammatory ligands. PMID- 8486685 TI - Granulocyte-macrophage colony-stimulating factor receptors alter their binding characteristics during myeloid maturation through up-regulation of the affinity converting beta subunit (KH97). AB - Acute myeloid leukemia blasts express dual affinity (high and low) granulocyte macrophage colony-stimulating factor (GM-CSF) binding, and the high affinity GM CSF binding is counteracted by excess interleukin-3 (IL-3). Neutrophils express a single class of GM-CSF-R with intermediate affinity that lack IL-3 cross reactivity. Here we demonstrate the differentiation associated changes of GM-CSF binding characteristics in three models representative of different stages of myeloid maturation. We find that high affinity GM-CSF binding is converted into intermediate affinity binding, which still cross-reacts with IL-3, beyond the stage of promyelocytes. During terminal maturation towards neutrophils, IL-3 cross-reactivity is gradually lost. We sought to determine the mechanism underlying the affinity conversion of the GM-CSF-R. Northern and reverse transcriptase-polymerase chain reaction analysis of GM-CSF-R alpha and -beta c (KH97) transcripts did not provide indications for the involvement of GM-CSF-R splice variants in the formation of the intermediate affinity GM-CSFR complex. In COS-cell transfectants with increasing amounts of beta c in the presence of a fixed number of GM-CSF-R alpha chains, the high affinity GM-CSF binding converted into intermediate affinity GM-CSF binding. These results are discussed in view of the concept that increasing expression of beta c subunits may cause alternative oligomerization of the GM-CSF-R alpha and -beta c subunits resulting in the formation of intermediate rather than high affinity GM-CSFR alpha.beta c complexes. PMID- 8486686 TI - Kinetic and spatial interrelationships between ganglioside glycosyltransferases and O-acetyltransferase(s) in human melanoma cells. AB - The melanoma-associated disialogangliosides 9(7)-O-acetyl-GD3 and 9(7)-O-acetyl GD2 have been structurally well characterized. However, the compartmentalization and sequence of action of the biosynthetic activities responsible for synthesizing these molecules remain obscure. Here, we have studied the spatial and temporal interrelationships among the activities responsible for the later stages of ganglioside biosynthesis and those for O-acetylation in cultured human melanoma cells. First, brefeldin A treatment was used to separate biosynthetic steps into compartments distal or proximal to the transport block imposed by the drug. In keeping with prior reports, GM2/GD2 synthase was consistently rendered inaccessible to its acceptors GM3 and GD3. In contrast, the effect on GD3 biosynthesis was cell line-specific. Synthesis of GD3 was nearly abrogated in two lines, while it accumulated in a third line. This indicates that the spatial organization of ganglioside processing activities can vary even between similar cell lines. However, in all cell lines studied, the ratio of 9(7)-O-acetyl-GD3 to GD3 was not changed by brefeldin A, indicating that the majority of ganglioside O acetyltransferase activity is co-localized with GD3 biosynthetic activity in the same Golgi subcompartment(s). As an alternative approach, Golgi-enriched fractions from melanoma cells were incubated with radiolabeled and nonlabeled nucleotide sugars or acetyl-CoA. In these preparations, biosynthesis is dependent upon the co-localization of appropriate sugar nucleotide transporters, glycosyltransferases, and acceptors that are endogenously present within intact topologically correct compartments. Incubations with CMP-Neu5Ac and acetyl-CoA corroborated the results with brefeldin A, co-localizing ganglioside O acetyltransferase activity in compartments where GD3 biosynthesis takes place. Analyses with CMP-Neu5Ac and UDP-GalNAc showed that GD2 and GD3 synthesis occur in partially overlapping compartments. Labeling with acetyl-CoA and UDP-GalNAc indicated that although labeled acetate can be transferred from acetyl-CoA directly to GD2, ganglioside O-acetyltransferase activity does not substantially overlap with the biosynthetic compartment(s) for GD2. Instead, O-acetyl-GD3 appears to be co-localized with the compartment of GD2 biosynthesis and serves as an acceptor for GD2 synthase. Thus, both 9-O-acetyl-GD3 and GD2 can be precursors of 9-O-acetyl-GD2, but apparently in distinct compartments. PMID- 8486687 TI - High level O-acetylation of sialic acids on N-linked oligosaccharides of rat liver membranes. Differential subcellular distribution of 7- and 9-O-acetyl groups and of enzymes involved in their regulation. AB - O-Acetylation of sialic acids has previously been considered an uncommon modification found on certain salivary mucins and neural gangliosides. We show here that glycosidically bound sialic acids from total membranes of rat liver have surprisingly high levels (approximately 20%) of O-acetylation at the 7- or 9 position. This O-acetylation is further enriched in N-linked oligosaccharides but is barely detectable in ganglioside fractions from the same tissue. The position of O-acetylation on the sialic acid side chain varies between different subcellular fractions. In particular, 7-O-acetylation was enriched in lysosomal membranes and 9-O-acetylation in plasma membranes, whereas Golgi membranes contained both types. This distribution fits with the ability of the rat liver sialate: O-acetyltransferase(s) to synthesize both 7- and 9-O-acetyl esters (Diaz, S., Higa, H. H., Hayes, B. K., and Varki, A. (1989) J. Biol. Chem. 264, 19416-19426) and the fact that 7-O-acetyl esters can migrate to the 9-position at physiological temperature but only under neutral or mildly alkaline conditions. Subcellular fractionation shows that sialate:O-acetyltransferase activity directed toward endogenous acceptors is enriched in Golgi fractions, whereas an intralumenal sialic acid-specific O-acetylesterase activity is not. The O acetyltransferase is labile and difficult to solubilize in the intact state and cannot be assayed with exogenous acceptors. However, a prelabeled [3H]acetyl intermediate can be solubilized from Golgi membranes with Triton X-100 and is stable for a prolonged time in the cold. In contrast to the transferase, the lumenal esterase is easily released in a stable and water-soluble form from membrane fractions by saponin permeabilization or repeated freeze-thaw. In keeping with this finding, differential subcellular fractionation and continuous sucrose gradients indicate that this enzyme is enriched in lysosomal fractions (see also the accompanying paper (Butor, C., Higa, H. H., and Varki, A. (1993) J. Biol. Chem. 268, 10207-10213). Based upon findings reported in this and previous studies, a model is proposed for the biosynthesis, maturation, and turnover of 7- and 9-O-acetyl esters on the sialic acids of N-linked oligosaccharides that are attached to membrane-bound proteins in the rat liver. PMID- 8486688 TI - Structural, immunological, and biosynthetic studies of a sialic acid-specific O acetylesterase from rat liver. AB - We have previously described a membrane-associated intralumenal sialic acid specific 9-O-acetylesterase (LSE) from rat liver (Higa, H. H., Manzi, A., and Varki, A. (1989) J. Biol. Chem. 264, 19435-19442). Unlike a cytosolic sialate: O acetylesterase (CSE) with similar specificity, the LSE carries N-linked oligosaccharides. A polyclonal monospecific antibody against homogenous LSE does not cross-react with the CSE. Monoclonal antibodies distinguish between the LSE and another N-glycosylated esterase that tends to partially co-purify with it. Amino-terminal sequencing of the LSE subunits indicates that it is distinct from previously described esterases and shows no homology to any other known proteins. In contrast, the esterase that partially co-purifies is similar but not identical to previously described "microsomal" esterases from rat liver. The LSE is also expressed in several hepatoma cell lines. Pulse-chase studies indicate that the two LSE subunits arise from a single precursor of approximately 65 kDa which yields a core polypeptide of apparent molecular mass approximately 53 kDa upon deglycosylation with peptide: N-glycosidase F. The protein quickly becomes partly resistant to endo-beta-N-acetylglucosaminidase H but remains sensitive to peptide: N-glycosidase F, indicating N-linked oligosaccharide processing during passage through the Golgi. After several hours, the precursor undergoes proteolysis, generating the mature heterodimeric protein of approximately 58 kDa, with subunits of approximately 38 and approximately 28 kDa. A portion of newly synthesized LSE is secreted into the medium intact, indicating that the cleavage normally takes place after diversion from the secretory pathway. These temporal changes and precursor-product distribution are reminiscent of some lysosomal acid hydrolases. In fact, immunofluorescence studies and Triton WR-1339 shift experiments suggest a lysosomal localization for this enzyme. Additional evidence for this, and the role of the LSE in O-acetylated sialic acid turnover are discussed in the accompanying paper (Butor, C., Diaz, S., and Varki, A. (1993) J. Biol. Chem. 268, 10197-10206). PMID- 8486689 TI - Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase epsilon. AB - The cDNA encoding the catalytic polypeptide of human DNA polymerase epsilon was cloned. The deduced amino acid sequence reveals that the catalytic polypeptide is 2257 amino acids in length and its calculated molecular mass is 258 kDa. A single RNA message of 7.5 kilobases was recognized by isolated cDNA clones. The identity of the cDNA was verified by direct amino acid sequencing of tryptic fragments derived from the catalytic polypeptide of the HeLa DNA polymerase epsilon. The primary structure comparison with multiple DNA polymerases indicates that human DNA polymerase epsilon catalytic polypeptide is a homolog of the yeast Saccharomyces cerevisiae DNA polymerase II catalytic polypeptide. The proteins are 39% identical. In the region containing known DNA polymerase consensus motifs, the identity is 63%. The expression of the mRNA encoding DNA polymerase epsilon is strongly dependent on cell proliferation. PMID- 8486690 TI - A novel negative element in the promoter of the mouse alcohol dehydrogenase gene Adh-1. AB - The mouse alcohol dehydrogenase gene, Adh-1, is expressed in a tissue-specific manner. We examined the promoter activity of a series of 5' deletions extending from bp -473 to -47 and demonstrated that there are positive regulatory elements between bp -229 and +54 and a negative regulatory element between bp -323 and 229. To identify the sequence of the negative regulatory element, gel retardation and DNase I footprint assays were performed using nuclear proteins from mouse liver and from a hepatoma cell line, H4IIE-C3. A specific protein-binding site covered bp -324 and -297. Within this region, we identified sites of close protein-DNA contact by methylation interference assays, located in the sequence TGGAAGTTTCAGGTT (nt -316 to -302). Site-directed mutagenesis of four protein-DNA contact sites within this sequence eliminated the specific protein-DNA binding, assayed by gel retardation, and restored expression of Adh-1 in transient transfection assays to the levels seen when the entire region containing the negative element was deleted. Thus, we have identified a negative regulatory element within the Adh-1 promoter. No homology was found between this negative element and other regulatory elements, suggesting that this is a novel negative element. PMID- 8486691 TI - LESP, an androgen-regulated lizard epididymal secretory protein family identified as a new member of the lipocalin superfamily. AB - The sperm coating lizard epididymal secretory protein (LESP) family forms a complex of nine elements that are specifically synthesized under androgenic control and secreted by the epididymal epithelial cells of the lizard Lacerta vivipara. We report here the cloning and sequencing of an 806-base pair full length cDNA (C731) encoding one of the elements of the LESP family. Southern blot hybridization analysis of lizard total genomic DNA revealed a complex band pattern, suggesting that LESPs are encoded by a multigenic family. The cDNA open reading frame of 516 nucleotides, starting at an ATG codon, encodes a protein precursor of 172 amino acids with a calculated M(r) = 19,500. The corresponding mature form of M(r) = 17,200 and pI = 5.2 has been identified as the element LESP IV, and presents significant similarities to the different members of the large lipocalin protein superfamily, and especially to mouse epididymal protein ESP I. Lipocalins are extracellular proteins that share a common basic framework for the transport of small hydrophobic molecules like retinoids, thus suggesting that LESPs could be such transporters into the epididymal fluid during the sperm maturation. PMID- 8486692 TI - Characterization of the DNA-binding domain of the mouse uterine estrogen receptor using site-specific polyclonal antibodies. AB - The DNA-binding domain of the mouse uterine estrogen receptor (ER) was characterized using site-specific polyclonal antibodies. The peptides used as antigens have sequences corresponding to amino acids 185-199 and 227-245, the two zinc finger regions of the DNA-binding domain of the human ER, and produced anti sera designated A-1542 and A-1554, respectively. Mouse uterine nuclear ER and salt-activated 4 S cytosol receptor, as well as 8 S untransformed cytosol receptor, were observed to react with the antisera by Western blot and sucrose density gradient centrifugation analyses indicating that the DNA-binding domain of the 8 S cytosol receptor is not completely masked by heat shock protein 90 or other proteins. Only A-1554 detected a nuclear-specific doublet form of the ER on Western blot analysis. In a gel shift assay, neither antisera altered the pattern of the nuclear ER interaction with the vitellogenin A2 estrogen response element (VRE). In contrast, antiserum A-1554 partially shifted the 8 S cytosol receptor VRE complex. This concurs with mutational analysis and x-ray crystallography studies with the human ER that have shown that the second finger is not in contact with the DNA. The results of the gel shift assay were confirmed by sucrose density gradient analysis using the same buffer conditions. The nuclear receptor-VRE complex did not react with either antisera, suggesting that when the dimeric nuclear receptor form binds the VRE, the specific receptor epitopes involved with the DNA binding may be blocked and unable to bind the antisera. The cytosol receptor-VRE complex reacted only partially with the second finger antisera A-1554, suggesting that on receptor monomers the second finger epitope is not completely blocked by DNA binding or dimer formation. PMID- 8486693 TI - Identification and cloning of GP-3 from rat pancreatic acinar zymogen granules as a glycosylated membrane-associated lipase. AB - The protein components of highly purified secretory granule membranes and the granule contents from rat exocrine pancreas were characterized by two-dimensional polyacrylamide gel electrophoresis, protein staining, lectin absorption, and Western blotting with anti-secretory protein antibodies. NH2-terminal amino acid sequence was obtained for a approximately 53-kDa glycoprotein denoted GP-3, present only in granule membrane preparations where it was resistant to washing with Na2CO3 and KBr. The sequence of this protein showed homology to pancreatic lipase but was distinct from the NH2-terminal sequence of a 50-kDa content protein presumed to be secretory lipase. Polymerase chain reaction amplification with degenerate oligonucleotide primers to GP-3 and secretory lipase gave partial length subclones that were used to isolate clones from a rat pancreas cDNA library. Dideoxy sequencing of full-length subclones of GP-3 revealed the predicted amino acid sequence for a mature protein of 452 amino acids with a potential N-linked glycosylation site and a deglycosylated molecular weight of 50,860. The GP-3 sequence possesses the serine esterase consensus sequence G-X-S X-G centered around Ser154 and the catalytic state triad Asp178-His265-Ser154 characteristic of pancreatic lipases. Northern blot analysis of various rat tissues showed GP-3 expression solely in pancreas. Comparison of GP-3 nucleotide and amino acid sequence, along with pancreatic lipases of various species including rat, shows extensive homologies to both proteins and reveals an underlying diversity in the pancreatic lipase family. Close homology is observed between GP-3 and a lipase molecule previously isolated from mouse cytotoxic T cells. PMID- 8486694 TI - Processing of the carboxyl 15-amino acid extension in the alpha-chain of fibrinogen. AB - The cDNA for the alpha-chain of human fibrinogen codes for 15 amino acids at the carboxyl terminus that are not found in the native protein circulating in plasma. In the present studies, experiments were designed to test whether the carboxyl extension was required for fibrinogen assembly or was simply the result of limited proteolysis and maturation of the protein during or following secretion. Baby hamster kidney cells were transfected with cDNAs coding for the alpha-, beta , and gamma-chains, and the recombinant fibrinogen secreted into the cell culture medium was identified either with an antibody against the mature molecule or with an antibody directed toward the carboxyl extension of the alpha-chain. The secreted protein contained primarily two species of alpha-chains, including one with the carboxyl extension and one that was the same as that in plasma fibrinogen. A mutant fibrinogen, in which Arg-611 at the putative cleavage site in the alpha-chain was converted to Gly, was also readily assembled, and, in this case, the protein was secreted with the alpha-chain carboxyl extension. Similarly, a mutant fibrinogen that completely lacked the carboxyl extension of the alpha-chain was assembled and secreted from the transfected baby hamster kidney cells. These two mutants with modified alpha-chains were readily clotted by thrombin and cross-linked by factor XIIIa. These results indicate that the alpha-chain carboxyl extension in fibrinogen is not required for assembly or secretion of the molecule. Accordingly, it was concluded that the cleavage of the alpha-chain removing the carboxyl-terminal 15 amino acids is a normal and specific processing event occurring during the maturation of the protein. PMID- 8486695 TI - Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells. AB - Peripheral myelin protein, 22 kDa (PMP22), is a myelin molecule associated with Schwann cells in peripheral nerves (Snipes, G. J., Suter, U., Welcher, A. A., and Shooter, E. M. (1992) J. Cell Biol. 117, 225-238). Mutations affecting the PMP22 gene have been implicated in the trembler mutation in mice (Suter, U., Welcher, A. A., Ozcelik, T., Snipes, G. J., Kosaras, B., Francke, U., Billings-Gagliardi, S., Sidman, R. L., and Shooter, E. M. (1992) Nature 356, 241-244; Suter, U., Moskow, J. J., Welcher, A. A., Snipes, G. J., Kosaras, B., Sidman, R. L., Buchberg, A. M., and Shooter, E. M. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 4382-4386) and Charcot-Marie-Tooth Disease in humans (Patel, P. I., Roa, B. B., Welcher, A. A., Schoener-Scott, R., Trask, B. J., Pentao, L., Snipes, G. J., Garcia, C. A., Francke, U., Shooter, E. M., Lupski, J. R., and Suter, U. (1992) Nature genet. 1, 159-165). In this report, we have studied PMP22 production in cultured rat Schwann cells. Schwann cells contain a 1.8-kilobase mRNA transcript coding for PMP22, and its production is up-regulated in vitro by forskolin. Metabolic labeling combined with immunoprecipitation methods using antibodies raised against synthetic peptides of PMP22 reveal that Schwann cells generate the protein from an 18-kDa precursor form which is post-translationally modified by N linked glycosylation. A second molecule (molecular mass, 48 kDa) that reacted with PMP22 antibodies was also detected in Schwann cells but is not related chemically to PMP22 as determined by pulse-chase labeling. Metabolic labeling of rat sciatic nerve and Western blot analyses of purified rat sciatic nerve myelin reveal that deglycosylation of PMP22 gives rise to an 18-kDa protein similar in size to that in Schwann cells. These results indicate that cultured Schwann cells may provide a good model in which to investigate the production and function of PMP22 and to establish the cellular basis for the protein's involvement in inherited peripheral neuropathies. PMID- 8486696 TI - Arginine residues of the globular regions of human C1q involved in the interaction with immunoglobulin G. AB - The immunoglobulin G binding site in the globular regions of human complement subcomponent C1q has been investigated by chemical modification of histidine residues with diethylpyrocarbonate and arginine residues with phenylglyoxal and cyclohexane-1,2-dione (CHD). Only the modification of arginine residues with CHD fulfills the requirements of a specific modification without unwanted side reactions. Specific modification of arginine residues with CHD results in loss of immune complex recognition without affecting the binding of C1r2S2 to form C1. The gross structure of C1q is not changed by CHD treatment, and immune complex binding is restored to 82% of the control upon NH2OH treatment. Enzymic digestion and isolation of the modified peptides indicate that the modification by CHD of 4 to 5 arginine residues (A162, B114, B129, C156, and possibly B163) per C1q globular "head" abolishes the ability of C1q to interact with immune complexes. These residues define two areas (and possible binding sites for IgG) on the globular region of C1q: B114-B129 (site 1) and A162-(B163)-C156 (site 2). Sequence comparison and solvent exposure predictive studies favor site 2 as the immunoglobulin G binding site on the globular regions of C1q, although the participation of site 1 cannot be ruled out. PMID- 8486697 TI - RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc. AB - The largest subunit of mammalian RNA polymerase II (RNAP II) contains at its carboxyl terminus an unusual domain consisting of 52 tandem repeats of the consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. This domain, designated the COOH terminal domain (CTD), is essential for viability and is extensively phosphorylated during the transition from preinitiation complex assembly to elongation (1). Indeed, phosphorylation of the CTD may play an important regulatory role in this transition. We show here that the CTD is also modified by a novel form of protein glycosylation, O-GlcNAc. This modification has been found on numerous transcription factors and other nuclear and cytosolic proteins (2). Glycopeptides obtained by proteolytic digestion of the CTD were purified by reverse-phase high performance liquid chromatography and sequenced. Results from such experiments suggest that glycosylation occurs at multiple sites throughout the CTD, similar to the phosphorylation of this domain. The carbohydrate, however, is not detectable on the phosphorylated form of the enzyme. This observation is consistent with the idea that phosphorylation and glycosylation are mutually exclusive modifications. The CTD of RNAP II, therefore, appears to exist in three distinct conformational states: unmodified, phosphorylated, and glycosylated. The differential modification of the CTD may play an important role in the regulated expression of genes transcribed by RNA polymerase II. PMID- 8486698 TI - Purification and characterization of a template-associated protein kinase that phosphorylates RNA polymerase II. AB - We have recently shown that a template-associated protein kinase, which phosphorylates the carboxyl-terminal domain (CTD) of RNA polymerase II, is a two component system. We describe here the purification of these two components to apparent homogeneity from human (HeLa) cell nuclear extract. Kinase component A has a 340-kDa native molecular mass, consists of a single large polypeptide, and contains the kinase active site. Kinase component B, which is identical to the Ku autoantigen, has a 180-kDa native molecular mass, and consists of apparently equimolar 67- and 83-kDa polypeptides. Component B stimulates the activity of component A, and under some conditions, confers DNA dependence on the reaction. The purified kinase converts the CTD to the multiply phosphorylated CTD0 form. Conversion occurs processively, and this processivity is an inherent property of component A. The in vitro phosphorylated CTD0 form contains approximately equimolar phosphoserine and phosphothreonine, but no detectable phosphotyrosine. PMID- 8486699 TI - cDNA cloning and expression of the human hepatic bile acid-binding protein. A member of the monomeric reductase gene family. AB - In human liver, we previously identified one isoform of dihydrodiol dehydrogenase activity that expresses high affinity bile acid binding (HBAB) with minimal 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity for bile acids. This protein may assist in the rapid intracellular transport of bile acids from the sinusoidal to the canalicular pole of the cell. We now report the cDNA cloning and bacterial expression of this novel, multifunctional protein. A 1252-base pair HBAB cDNA was cloned from a HepG2 lambda GT11 library using a rat hepatic bile acid binder cDNA probe. Bacterial expressed recombinant HBAB oxidized racemic trans dihydrodiol benzene (0.455 mumol NADPH/mg/min) with minimal 3 alpha-HSD activity for bile acids (< 0.003 mumol NADPH/mg/min). Lithocholic acid and chenodeoxycholic acid dissociation constants as determined by displacement of the fluorescent probe, bis-1-anilino-8 sulfonate, were higher than those previously reported for the native protein (1 microM versus 10 nM). Significant amino acid sequence homology was found with the human chlordecone reductase, bovine prostaglandin F synthetase, and rat hepatic-3 alpha-HSD suggesting, that HBAB is also a member of the recently identified, monomeric oxidoreductase gene family. Future studies will define the physiologic significance of this novel, multifunctional protein in bile acid transport and xenobiotic metabolism. PMID- 8486700 TI - Uptake and degradation of glyceraldehyde-3-phosphate dehydrogenase by rat liver lysosomes. AB - The molecular mechanisms involved in the degradation of individual cellular proteins are probably unique and characteristic. We have investigated in rat liver the degradation of glyceraldehyde-3-phosphate dehydrogenase, an abundant cytosolic enzyme of the glycolytic pathway. Immunoblot analysis of isolated liver lysosomes from rats treated with lysosomal inhibitors show that this protein is degraded, at least in part, by a lysosomal pathway. This pathway was further investigated by incubating the enzyme with lysosomes in a cell-free system, followed by proteolysis measurements, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of lysosomes, and electron microscopic immunocytochemistry. We postulate that the degradative mechanism of glyceraldehyde-3-phosphate dehydrogenase includes a temperature-dependent lysosomal pathway, different from classical nonspecific macroautophagy. The postulated pathway involves: binding of the enzyme to the lysosomal membrane, entry into the lysosomal matrix, and degradation. This cell-free system, which can also incorporate in vitro synthesized proteins, should allow further advances toward clarifying the complex signals that regulate protein degradation as well as its close interrelationship with protein synthesis. PMID- 8486701 TI - A cationic region of the platelet-derived growth factor (PDGF) A-chain (Arg159 Lys160-Lys161) is required for receptor binding and mitogenic activity of the PDGF-AA homodimer. AB - Platelet-derived growth factor-AA and -BB homodimers and -AB heterodimers bind with high affinity to the platelet-derived growth factor (PDGF) alpha-receptor. Basic polypeptides such as polylysine and protamine sulfate compete with PDGF for receptor binding, suggesting a role for ligand positive charge in the binding interaction. A pentapeptide amino acid sequence with a cationic tripeptide core is perfectly conserved between the A- and B-chains (Val158-Arg159-Lys160-Lys161 Pro162) and was therefore considered as a possible alpha-receptor-binding domain. We have investigated the functional importance of positive charge within this region of the PDGF A-chain by using site-directed mutagenesis to convert the cationic core amino acids to the acidic sequence triglutamic acid. cDNAs encoding wild-type (PDGF-AAwt) and charge mutant (PDGF-AAcm) proteins were expressed following stable transfection of Chinese hamster ovary cells. Proper assembly and secretion of PDGF-AAcm was verified by metabolic labeling with [35S]cysteine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis analysis under nonreducing and reducing conditions. PDGF-AAcm was secreted as two major species of disulfide-linked A-chain homodimers identical in molecular mass to those observed for PDGF-AAwt (32 and 35 kDa). Secreted PDGF-AAwt and PDGF-AAcm proteins were purified to homogeneity and subjected to structural and functional analyses. Compared to purified PDGF-AAwt, PDGF-AAcm displayed a marked reduction in both binding affinity for PDGF alpha-receptors and mitogenic activity in Swiss 3T3 cells. Large reductions were also observed in the ability of semipurified PDGF AAcm to stimulate calcium influx and the production of inositol phosphates. Measurement of circular dichroism spectra of highly purified PDGF-AAcm and PDGF AAwt revealed no significant difference in secondary structure. Collectively, these results indicate that the cationic Arg159-Lys160-Lys161 region plays a critical role in the biological activity of PDGF-AA by direct participation in ligand binding to the PDGF alpha-receptor. PMID- 8486702 TI - Interleukin-6 signal communication to the alpha 1-acid glycoprotein gene, but not junB gene, is impaired in HTC cells. AB - In the rat hepatoma (HTC) cell line, transcription of the alpha 1-acid glycoprotein (AGP) gene is prominently stimulated by dexamethasone. Although interleukin (IL)-1 and IL-6 synergistically enhance expression of the AGP gene in liver, they have no detectable effect on this gene in HTC cells. Nevertheless, HTC cells have mRNA encoding the IL-6 receptor subunits and respond to IL-6 by increasing expression of the junB gene. The mRNA for the 80-kDa IL-6 receptors is increased severalfold following dexamethasone treatment. Even with elevated IL-6 receptor expression, no IL-6 regulation of the AGP gene is observed. The lack of response to IL-6 is also found with the transfected AGP gene sequence, suggesting the absence of specific trans-acting factors. Since IL-6 promotes only a minimal stimulation of the CCAAT/enhancer-binding protein beta, HTC cells lack the indirect IL-6 signaling pathway to acute phase plasma protein genes that has been found to be crucial in other hepatoma cell lines. Considering that a similar IL-6 regulation of the junB gene is manifested in HTC cells and normal liver, a separate IL-6 signal-transducing pathway controlling the AGP gene is assumed to be missing in HTC cells. PMID- 8486703 TI - Expression of the core lipopeptide of the glycopeptidolipid surface antigens in rough mutants of Mycobacterium avium. AB - Toward studying the genetics, biosynthesis, and roles in the pathogenesis of the dominant surface glycopeptidolipid antigens of Mycobacterium avium, rough colony variants of M. avium serovar 2 were picked, cultured in quantity, and their lipid composition examined. Two of the rough (Rg) variants, Rg-3 and Rg-4, were devoid of glycopeptidolipids or any more elemental structures and thus were similar to those described previously. Two others, Rg-0 and Rg-1, each contained two novel lipopeptides, devoid of any of the carbohydrate substituents that confer serotypic activity on the glycopeptidolipids. The application of gas chromatography, fast atom bombardment-mass spectrometry and 1H NMR to lipopeptide I established the structure C32:2-beta-OH-fatty acyl-D-Phe-D-allo-Thr-D-Ala-L alaninol. Lipopeptide II represented a minor variation of this structure: C32:1 beta-OH-fatty acyl-D-Phe-D-allo-Thr-D-Ala-L-alaninol. These newly discovered lipopeptides are identical to the fatty acyl-tripeptide-amino alcohol "core" component of the glycopeptidolipids of the M. avium complex, and thus the Rg-0 and Rg-1 variants represent a form of "deep rough" mutation in M. avium. Separately, we report that these rough variants of M. avium differ genetically from the smooth, virulent form by major deletions of portions of the genes responsible for glycopeptidolipid synthesis (Belisle, J. T., Klaczkiewicz, K., Brennan, P. J., Jacobs, W. R., Jr., and Inamine, J. M. (1993) J. Biol. Chem. 268, 10517-10523). The isolation of different sets of spontaneous mutants of M. avium differentially defective in the capacity to synthesize glycopeptidolipids provides the means to explore their biosynthesis and roles in opportunistic pathogenesis. PMID- 8486704 TI - Rough morphological variants of Mycobacterium avium. Characterization of genomic deletions resulting in the loss of glycopeptidolipid expression. AB - Previously, a gene cluster, termed ser2, which encodes for the synthesis of the specific oligosaccharide of the glycopeptidolipid antigen of Mycobacterium avium serovar 2 strain TMC 724, was defined. DNA probes from this cloned ser2 gene cluster have now been used to clone and characterize the ser2 region from a strain of M. avium which produces rough and smooth colony forms and to identify the genetic differences between these morphotypes. Interstrain differences were seen to exist between the ser2 gene cluster of M. avium strains TMC 724 and 2151. In addition, two distinct rough (Rg) genotypes of strain 2151 were defined by this analysis. The first of these, present in the M. avium Rg-0 and Rg-1 variants, was attributed to a deletion of approximately 28 kilobases from smooth variants, including the entire ser2 gene cluster. This particular deletion is thought to be mediated by recombination between repetitive sequences that flank both sides of the 28-kilobase excised region. The second genotype, seen in M. avium Rg-3 and Rg-4 variants, results from the deletion of an undefined amount of DNA from the right of the ser2 gene cluster. Reported separately (Belisle, J. T., McNeil, M. R., Chaterjee, D., Inamine, J. M., and Brennan, P. J. (1993) J. Biol. Chem. 268, 10510-10516) are the results of biochemical analyses of the glycopeptidolipid/lipopeptide population of the Rg genotypes which revealed that Rg-0 and Rg-1 possess lipopeptides devoid of all of the sugars of the glycopeptidolipids and are obviously biosynthetic precursors of the glycopeptidolipids. These studies help formulate a definition of the physiological effects of glycolipid expression, the biosynthetic and genetic mechanisms involved in their formation, and toward an understanding of the role of M. avium as a serious opportunistic pathogen. PMID- 8486705 TI - Eukaryotic translation initiation factor 5 from Saccharomyces cerevisiae. Cloning, characterization, and expression of the gene encoding the 45,346-Da protein. AB - Eukaryotic translation initiation factor 5 (eIF-5) catalyzes hydrolysis of GTP bound to a 40 S ribosomal initiation complex with the subsequent joining of a 60 S ribosomal subunit to form an 80 S initiation complex. The yeast gene that encodes eIF-5, designated TIF5, has been isolated and expressed in Escherichia coli to yield a catalytically active eIF-5 protein. TIF5 is a single-copy gene that maps on yeast chromosome XVI and is essential for cell viability. The gene contains an intron-free open reading frame that encodes a protein of calculated M(r) 45,346 in close agreement with the apparent molecular weight of eIF-5 isolated from yeast cells. Sequence analysis of the gene reveals several interesting features. First, the presence of two in-frame translational start sites located 51 base pairs apart suggests the possibility that two proteins, differing by an amino-terminal extension of 17 amino acids, could be generated from the TIF5 gene via differential translational starts. This would explain the presence, in yeast cell lysates, of two forms of eIF-5 differing in molecular weight by about 2,000. Second, the predicted amino acid sequence of eIF-5 contains sequence motifs characteristic of proteins of the GTPase superfamily. PMID- 8486706 TI - Differential translocation of protein kinase C isozymes by thrombin and platelet derived growth factor. A possible function for phosphatidylcholine-derived diacylglycerol. AB - The translocation of protein kinase C (PKC) from the cytosolic to the particulate fraction in IIC9 fibroblasts has been studied to define the functions of 1,2 diacylglycerol (DAG) derived from the hydrolysis of phosphatidylinositol 4,5 bisphosphate (PIP2) and phosphatidylcholine (PC). alpha-Thrombin caused a biphasic change in DAG, with two peaks at 15-60 s and 5-15 min, derived from PIP2 and PC, respectively, while platelet-derived growth factor (PDGF) induced a monophasic DAG increase from PC at 5-15 min. alpha-Thrombin also induced a rapid, but transient, increase of inositol 1,4,5-trisphosphate and cytosolic Ca2+, whereas PDGF did not. Three PKC isozymes, alpha, epsilon, and zeta, were identified by Western blotting in IIC9 cells and were mainly localized in the cytosol. A fraction of cytosolic PKC alpha was rapidly translocated by alpha thrombin at 15 s, but its membrane association was lost within 1 min. PKC epsilon was also rapidly translocated; however, its membrane association was sustained for almost 60 min. PKC zeta was not translocated by alpha-thrombin or phorbol 12 myristate 13-acetate. PDGF translocated PKC epsilon at 5 min but had little effect at 15 s and did not translocate PKC alpha or zeta. Incubation with Bacillus cereus PC- or phosphatidylinositol-specific phospholipase C, which increased DAG but not phosphatidic acid, stimulated translocation of PKC epsilon, but not PKC alpha or zeta. Addition of chelators to inhibit the rise in intracellular Ca2+ largely blocked PKC alpha translocation induced by alpha thrombin but had no effect on PKC epsilon translocation. Addition of ionomycin allowed alpha-thrombin to induce PKC alpha translocation at 5 min. PKC alpha translocation was mimicked by 1,2-dioctanoylglycerol plus ionomycin, but not by either alone. On the other hand, PKC epsilon was translocated by the DAG alone. These results support the conclusion that PIP2 hydrolysis activates both PKC alpha and epsilon at 15 s, whereas PC hydrolysis activates only PKC epsilon at 5 min. The differential activation at 5 min can be attributed to the failure of PC hydrolysis to increase Ca2+ and not to a difference in the molecular species of DAG derived from the phospholipids. PMID- 8486707 TI - EBP-80, a transcription factor closely resembling the human autoantigen Ku, recognizes single- to double-strand transitions in DNA. AB - We have previously reported the purification and characterization of the transcription factor EBP-80 (Falzon, M., and Kuff, E. L. (1989) J. Biol. Chem. 264, 21915-21922). EBP-80 mediates the DNA methylation effect on transcription from an endogenous proviral long terminal repeat. Here we show that EBP-80 is very similar if not identical to the Ku autoantigen, a heterodimeric nuclear protein first detected by antibodies from autoimmune patients (Mimori, T., Akizuki, M., Yamagata, H., Inada, S., Yoshida, S., and Homma, M. (1981) J. Clin. Invest. 68, 611-620). A number of laboratories have shown that the Ku protein complex binds to free double-stranded DNA ends. In this study, we have examined the binding properties of EBP-80. EBP-80 binds single-stranded DNA with low affinity. Binding to random sequence double-stranded DNA depends on the length of the duplex and is optimal with oligomers of 30 and 32 base pairs; the protein complexes formed with these oligomers have Kd values of 15-20 pM. It binds with comparable high affinities to blunt-ended duplex DNA, to duplex DNA ending in hairpin loops, and to constructs in which an internal segment of duplex DNA is flanked by single-strand extensions. EBP-80 also interacts effectively with circular duplex molecules containing a 30-nucleotide single-stranded region (gap) or a double-stranded segment of nonhomology (bubble), but only weakly with the corresponding closed circular construct made up entirely of duplex DNA. EBP-80 prefers A/T to G/C ends. The binding properties of EBP-80 are consistent with the hypothesis that is recognizes single- to double-strand transitions in DNA. A model is presented for the interaction of EBP-80 with its target sequence in the proviral long terminal repeat. PMID- 8486708 TI - Complete selective absence of protamine P2 in humans. AB - Male sterility due to abnormal sperm morphology or motion has been widely reported, although relatively little has been published on the sperm nuclear protein abnormalities. We report the first cases worldwide of infertile patients having a complete selective absence of protamine P2 in the sperm nucleus. This provides a selective phenotype that will aid understanding of the mechanisms of synthesis, processing, or function of the P2 protamines. In addition, it is of marked immediate relevance to medicine as it allows the diagnosis of this type of human male sterility and the opportunity to understand the basis of this defect. PMID- 8486709 TI - Analysis of the sequence requirements for glycosylphosphatidylinositol anchoring of Saccharomyces cerevisiae Gas1 protein. AB - The Saccharomyces cerevisiae Gas1 protein is synthesized as a precursor with a hydrophobic extension at the carboxyl terminus which is removed and replaced with an inositol containing glycolipid that anchors the protein to the plasma membrane. We performed saturation mutagenesis on the anchor attachment site (Asn506) and showed that only a subset of amino acids with small side chains could act as substrates for peptide cleavage and glycolipid addition. After Asn, which is the most efficient anchor attachment site, Ser, Gly, Ala, Asp, and Cys function with decreasing effectiveness. Mutational analysis also revealed that the 2 adjacent amino acids to the carboxyl side of the anchor attachment site are important for efficient anchoring. These two amino acids should have relatively short side chains with the second position being more critical. Analysis of the region between the anchor attachment site and the carboxyl-terminal hydrophobic region indicated that this region may not simply perform a spacer function. PMID- 8486710 TI - Vacuolar ATPase mutants accumulate precursor proteins in a pre-vacuolar compartment. AB - The vacuole of the yeast Saccharomyces cerevisiae contains a proton-translocating ATPase that acidifies the vacuolar lumen and generates an electrochemical potential across the vacuole membrane. Strains with chromosomal disruptions of the genes encoding the A, B, and c subunits of the vacuolar ATPase accumulate precursor forms of the vacuolar membrane protein alkaline phosphatase, and the soluble vacuolar hydrolases carboxypeptidase Y and proteinase A. We have found that the intracellular precursors in delta vat strains accumulate within the secretory pathway at some point before delivery to the vacuole but after transit to the Golgi complex. Purified vacuoles from delta vat cells do not contain the precursor forms of carboxypeptidase Y or alkaline phosphatase. In addition, vacuolar hydrolase-invertase hybrid proteins are inefficiently delivered to the vacuole in delta vat strains as demonstrated by vacuole isolation. Further subcellular fractionation to separate organelles indicate that significant amounts of the carboxypeptidase Y-invertase and alkaline phosphatase-invertase hybrid proteins are located in the late Golgi complex and/or post Golgi compartments. PMID- 8486711 TI - Template activating factor I, a novel host factor required to stimulate the adenovirus core DNA replication. AB - The adenovirus (Ad) genome in virion exists in the form of the Ad core, which is a complex of Ad DNA and viral basic proteins. The Ad core supported only initiation and limited elongation in DNA replication in a cell-free system which was developed for DNA replication of naked Ad DNA. We found that addition of a cytoplasmic fraction from uninfected HeLa cells on the top of the system stimulated Ad core DNA replication, although it had no effect on DNA replication of naked Ad DNA. The factor stimulating Ad core DNA replication, designated as template activating factor I (TAF-I), was purified by successive steps of ammonium sulfate precipitation, column chromatographies on phosphocellulose and Q Sepharose, and glycerol density gradient centrifugation. SDS-polyacrylamide gel electrophoresis of the purified fraction revealed the presence of proteins with molecular masses of 41 and 39 kDa. TAF-I stimulated both initiation and elongation in Ad core DNA replication. Judging from its behavior in purification steps, TAF-I could be acidic. These findings suggest that TAF-I stimulates Ad core DNA replication by interaction with viral basic core proteins. PMID- 8486712 TI - Structural and functional analyses of the Arg-Gly-Asp sequence introduced into human lysozyme. AB - To determine the functional conformation of the Arg-Gly-Asp (RGD) sequence, we have constructed mutant proteins by inserting 4-12 amino acid residues from the RGD region of human fibronectin between Val74 and Asn75 of human lysozyme. RGDS-, GRGDSP-, TGRGDSPA-, VTGRGDSPAS-, and AVTGRGDS-PASS-introduced mutant lysozymes were expressed in yeast, purified, and designated as RGD4, -6, -8, -10, and -12, respectively. Using baby hamster kidney cells, RGD8, RGD10, and RGD12 were shown to possess high cell adhesion activity nearly equal to 10% of human vitronectin activity. RGD4 and RGD6 exhibited somewhat lower cell adhesion activity. The activities of these mutant proteins were inhibited by the addition of either GRGDSP peptide or polyclonal antibody against vitronectin receptor, as was the case for the vitronectin activity. The results suggest that the cell adhesion signals are transduced to cells through the interaction with the vitronectin receptor. The three-dimensional structures of RGD4 and RGD8 were determined at 1.8-A resolution by x-ray crystallography. A model of the inserted region in RGD4 could be built in the electron density map, but the positions of the preceding residues, Ala73-Val74, were uncertain. The inserted region in RGD8 did not demonstrate continuous electron densities. The results suggest that these RGD sequence-containing regions are highly flexible and that such flexibility could allow the conformation of the RGD regions to be induced to fit into the binding pocket of the integrin receptor. PMID- 8486713 TI - Muscle-specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle. AB - We previously identified a third type of the calpain large subunit named p94 as a cDNA whose mRNA is expressed exclusively in skeletal muscle at levels approximately 10-fold more abundant than those of the conventional calpain subunit. Rat skeletal muscle fractions were screened by two anti-peptide antibodies raised against two specific sequences in p94, but the p94 protein could not be found. To examine this apparent discrepancy between the amounts of mRNA and protein, wild-type p94 was expressed in COS cells. Although p94 mRNA was expressed normally in COS cells, only very small amounts of the protein and its presumed degradation products were detected by the antibodies described above. A series of COOH-terminal deletion mutants was constructed and expressed in COS cells and L8 cells, a rat myoblast cell line. When IS2, one of the specific regions of p94, was completely eliminated, the truncated p94 proteins were expressed normally, and the amount of the expressed proteins was at least 100 fold higher than with wild-type p94. Moreover, when site-directed mutagenesis was introduced to change the presumed active-site cysteine of p94 to serine or alanine, the mutated p94 proteins were highly expressed like the IS2-deleted mutants. These results indicate the following. 1) The mRNA for p94 is normally transcribed in COS, L8, and muscle cells; 2) the p94 protein becomes active in the cytosol immediately after translation; 3) the p94 protein virtually disappears from cells by autocatalytic degradation; and 4) the p94-specific IS2 region plays an important role in this degradation. In vitro translation experiments support this idea. Furthermore, p94 shows nuclear localization when expressed in COS cells. The physiological function of p94 in muscle is discussed on the basis of the analysis of these transfectants. PMID- 8486714 TI - Methyl jasmonate-regulated translation of nuclear-encoded chloroplast proteins in barley (Hordeum vulgare L. cv. salome). AB - The naturally occurring plant growth regulator (-)-jasmonic acid methyl ester (JaMe) induces the formation of novel abundant proteins in excised barley leaf segments. Concomitantly, this substance depresses the translation of most preexisting ("control") leaf mRNAs, including those for nuclear-encoded chloroplast proteins such as the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (SSU, rbcS gene product) and several light harvesting chlorophyll protein complex apoproteins (LHCPs, cab gene products). The changes in protein synthesis observed for SSU and LHCPs did not correspond to equivalent alterations in the rbcS and cab transcript levels. Analysis of polysome associated in vitro translatable and hybridizable mRNAs, however, demonstrated a restriction of rbcS and cab transcripts to smaller polysomes in JaMe-exposed leaf tissues, in comparison to water-treated tissues. Since treatment of JaMe incubated leaf segments with cycloheximide prior to harvest led to a shift of both transcripts toward larger polysomes, a hormone-induced impairment of chain initiation is assumed to lower translation of SSU and LHCP in situ. In contrast, the mRNA for plastid leucyl-tRNA synthetase (LRS1, lrs1 gene product) neither changed its abundance nor its association with polysomes in JaMe-treated leaves and was translated into the corresponding polypeptide. Together, our results highlight a remarkable variability of nuclear gene expression in response to plant growth regulators of the methyl jasmonate type. PMID- 8486715 TI - Oligomeric structure of bacteriophage T7 DNA primase/helicase proteins. AB - The oligomeric structure of bacteriophage T7 gene 4 helicase/primase proteins was investigated using protein cross-linking and high pressure gel-filtration chromatography. Studies were carried out with both 4A' and 4B proteins. 4A' is a M64L mutant of 4A which has similar helicase and primase activities as the wild type mixture of 4A and 4B proteins (Patel, S. S., Rosenberg, A. H., Studier, F. W., and Johnson, K. A. (1992) J. Biol. Chem. 267, 15013-15021), and 4B is the smaller protein which has only helicase activity. Chemical cross-linking of 4A' and 4B proteins with dimethyl suberimidate resulted in cross-linked species ranging from dimers to hexamers and beyond. The cross-linking time course, however, indicated that hexamers were the predominant species to accumulate in both 4A' and 4B proteins. The effect of MgNTP and DNA binding on oligomerization of the gene 4 proteins was investigated using high pressure gel-filtration chromatography at increasing protein concentrations. In the absence of added ligands, close to 100 microM protein concentrations were required to form stable oligomers beyond dimers. However, in the presence of Mg-beta, gamma-methylene deoxythymidine triphosphate (nonhydrolyzable analog of dTTP), 4A' and 4B protein assembled into stable hexamers at protein concentrations less than 8 microM. Addition of single-stranded DNA further stabilized the hexamer structure. Therefore, in the presence of a 60-nucleotide-long single-stranded DNA, hexamers were observed at protein concentrations as low as 0.2 microM. Nuclease protection experiments indicated that the 4A' and 4B hexamers protect about 60-65 bases of single-stranded DNA. PMID- 8486716 TI - Molecular characterization of the band 3 protein from Southeast Asian ovalocytes. AB - Southeast Asian ovalocytosis (SAO) is a hereditary form of elliptocytosis resulting in rigid, oval-shaped erythrocytes resistant to invasion by malaria parasites. The molecular defect is due to deletion of codons 400-408, encoding a 9-amino-acid sequence located at the boundary between the cytosol and the first transmembrane segment in Band 3, the erythrocyte anion transport protein. We have carried out an extensive characterization of Band 3 isolated from SAO erythrocytes which contain about 50% mutant Band 3. A slightly higher proportion of Band 3 in SAO erythrocytes was left associated with the cytoskeleton after extraction of ghost membranes with non-ionic detergents. Size exclusion high performance liquid chromatography analysis showed that SAO Band 3 contained a higher proportion of tetramers relative to dimers (50% tetramer) than normal Band 3 (33% tetramer). The circular dichroism spectrum of Band 3 from SAO erythrocytes was very similar to the spectrum for normal Band 3. Enzymatic deglycosylation and tomato lectin binding showed that SAO Band 3 lacked the polylactosaminyl oligosaccharide found on normal Band 3. SAO Band 3 was unable to bind the anion transport inhibitor 4-benzamido-4'-aminostilbene-2,2'-disulfonate, suggesting a dramatic alteration in the inhibitor binding site. In conclusion, deletion of 9 amino acids from Band 3 on the cytosolic side of the membrane affects the properties (glycosylation and inhibitor binding) of Band 3 on the opposite side of the membrane without dramatic changes in the secondary and quaternary structure of the protein. PMID- 8486717 TI - Identification of a single-stranded DNA-binding protein that interacts with an S1 nuclease-sensitive region in the platelet-derived growth factor A-chain gene promoter. AB - We previously observed that transcription of the platelet-derived growth factor (PDGF) A-chain gene is enhanced in cells stimulated by PDGF through a serum response element (SRE) in its 5'-flanking sequence. We now show that the region of the SRE is sensitive to S1 nuclease in vitro. We also identify a single stranded DNA-binding protein in HeLa cell nuclear extracts that binds to the noncoding strand of the PDGF A-chain SRE but not to its double-stranded counterpart or to the single-stranded coding sequence. Competition assays using oligonucleotides with sequence-specific mutations that diminished or eliminated detectable complex formation were used to establish the specificity of this protein/DNA interaction. Remarkably, the sequence-specific single-stranded binding protein binds to this region only when it is highly supercoiled. The data suggest that the single-stranded DNA-binding protein specifically interacts with a highly supercoiled region of the PDGF A-chain promoter and that this interaction may have a role in the transcriptional regulation of this gene. PMID- 8486718 TI - A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. AB - Onconase, or P-30, is a protein initially purified from extracts of Rana pipiens oocytes and early embryos based upon its anticancer activity both in vitro and in vivo. It is a basic single-chain protein with an apparent molecular mass of 12,000 daltons and is homologous to RNase A. In cultured 9L glioma cells, onconase inhibits protein synthesis with an IC50 of about 10(-7) M. The inhibition of protein synthesis correlates with cell death determined by clonogenic assays. 125I-Labeled onconase binds to specific sites on cultured 9L glioma cells. Scatchard analysis of the binding data shows that onconase appears to bind to cells with two different affinities, one with a Kd of 6.2 x 10(-8) and another of 2.5 x 10(-7) M. Each cell could bind about 3 x 10(5) molecules of onconase at each of the two affinity sites. The low affinity Kd is similar to the IC50 for onconase toxicity. Onconase also demonstrates a saturability of cytotoxicity at a concentration that would saturate the low affinity binding site. Incubation at 4 degrees C increased the binding of onconase to cells relative to 37 degrees C binding and also increased the sensitivity of cells to onconase toxicity, indicating that receptor binding may be an initial step in cell toxicity. Onconase cytotoxicity can be blocked by metabolic inhibitors, NaN3 and 2-deoxyglucose, and cytotoxicity is potentiated 10-fold by monensin. Ribonuclease activity appears necessary for onconase toxicity because alkylated onconase, which only retains 2% of the ribonuclease activity, was at least 100 fold less potent in inhibiting protein synthesis in cells. Onconase inhibition of protein synthesis in 9L cells coincides with the degradation of cellular 28 S and 18 S rRNA. In contrast to RNase A, onconase is resistant to two RNase inhibitors, placental ribonuclease inhibitor and Inhibit-Ace. Northern hybridization with placental ribonuclease inhibitor cDNA probe indicates that 9L glioma cells contain endogenous placental ribonuclease inhibitor mRNA. Based on these results, we propose that onconase toxicity results from onconase binding to cell surface receptors, internalization to the cell cytosol where it degrades ribosomal RNA, inhibiting protein synthesis and causing cell death. PMID- 8486719 TI - Effect of sequence, adduct type, and opposing lesions on the binding and repair of ultraviolet photodamage by DNA photolyase and (A)BC excinuclease. AB - The cis,syn and (6-4) products of dipyrimidine sites are the major mutagenic and lethal UV photoproducts in DNA. To investigate their relative susceptibilities to repair and other factors such as sequence context and lesions in the complementary strand that might influence repair efficiencies, we constructed 49 mer duplexes containing site-specific photoproducts of thymidylyl(3',5')thymidine sites at central locations. Using these substrates, we measured the binding of Escherichia coli DNA photolyase to cis,syn dimers in four sequence contexts and to two cis,syn dimers in close proximity and on opposing strands. We found that the sequence within a 10-base pair region had little effect on binding and that two enzyme molecules bound to substrate containing two dimers in the 5'-staggered orientation, but not in the 3'-staggered one. Similarly, the excision of a cis,syn dimer by (A)BC excinuclease was not influenced by the sequence in the immediate vicinity of the dimer, and the enzyme was active on 5'-staggered cis,syn dimers, but not on 3'-staggered ones. Of special significance, we found that (A)BC excinuclease removed the cis,syn, trans,syn-I, (6-4), and Dewar photoproducts at vastly differing relative rates of 1:6:9:9, respectively. PMID- 8486720 TI - ATP synthases. Structure, reaction center, mechanism, and regulation of one of nature's most unique machines. PMID- 8486721 TI - A pentapeptide from type I procollagen promotes extracellular matrix production. AB - The NH2 and COOH propieces of fibril-forming collagens are cleaved off extracellularly and have been implicated in feedback regulation of their own synthesis. Recently, we showed that a subfragment of the carboxyl-terminal propeptide of type I collagen (residues 197-241) dramatically augments extracellular matrix production in subconfluent fibroblasts. This stimulation of type I collagen, type III collagen, and fibronectin production occurred in a dose and time-dependent manner with no effect on total protein synthesis or on the ratio of secreted proteins to cell-associated proteins (Katayama, K., Seyer, J.M., Raghow, R., and Kang, A.H. (1991) Biochemistry 30, 7097-7104). In the present report, we have extensively dissected this subfragment of the propeptide and found that the pentapeptide Lys-Thr-Thr-Lys-Ser (residues 212-216) is the minimum sequence necessary for potent stimulation of collagen and fibronectin production in a variety of mesenchymal cells. We postulate that the extracellular matrix production in fibroblasts may be subject to either positive or negative feedback regulation depending on the repertoire of specific proteases during postinflammatory tissue regeneration and fibrosis. PMID- 8486722 TI - Interaction of myristoylated alanine-rich protein kinase C substrate (MARCKS) with membrane phospholipids. AB - A major in vivo substrate of Ca(2+)-phospholipid-dependent protein kinase (MARCKS) shows phosphorylation-dependent translocation between the cytoplasmic and the membrane fractions. The mechanism of the translocation was studied with purified MARCKS and various membranes. MARCKS was found to bind to pure phospholipid membranes as well as to the synaptic vesicle membranes. Although the interaction of MARCKS with the latter was phosphorylation-dependent, phosphorylation by protein kinase C showed no significant effect on the binding to the phosphatidylcholine liposomes. However, when phosphatidylserine was included in the membranes, the association became phosphorylation-dependent. A synthetic phosphorylation domain peptide showed a similar phosphorylation dependent interaction with the negatively charged liposomes. Phosphatidylserine but not phosphatidylcholine inhibited phosphorylation of MARCKS by protein kinase C. MARCKS seems to bind to the biomembranes through two binding sites: the N terminal myristoyl moiety and the basic phosphorylation domain of amphiphilic nature. Phosphorylation of this domain lowers its affinity to phosphatidylserine and makes the whole molecule strongly negatively charged, which causes its dissociation from the membranes. PMID- 8486723 TI - A comparative analysis of the kinetic mechanism and peptide substrate specificity of human and Saccharomyces cerevisiae myristoyl-CoA:protein N myristoyltransferase. AB - Human myristoyl-CoA:protein N-myristoyltransferase (hNmt) catalyzes the transfer of myristate from CoA to the amino-terminal Gly residue of a number of cellular proteins involved in signal transduction pathways, to structural and nonstructural proteins encoded by retroviruses, hepadnaviruses, picornaviruses, and reoviruses, as well as to several transforming tyrosine kinases. hNmt has been purified 230-fold from an erythroleukemia cell line. The monomeric enzyme has no associated methionyl aminopeptidase activity. To determine the enzyme's kinetic mechanism, we examined the effect of covariation of subsaturating concentrations of myristoyl-CoA and peptide substrate on initial velocity. Double reciprocal plots excluded a double displacement (ping-pong) mechanism. Product inhibition studies indicated that CoA was a noncompetitive inhibitor against myristoyl-CoA and a mixed-type inhibitor against peptide substrates. Together these results are consistent with a sequential ordered mechanism where, in a typical catalytic cycle, myristoyl-CoA binds to apoenzyme before peptide followed by release of the CoA and then myristoylpeptide products. This kinetic mechanism is identical to that described for Saccharomyces cerevisiae N-myristoyl transferase (Nmt1p) and emphasizes the impact that regulation of myristoyl-CoA pool size and accessibility may have in modulating protein N-myristoylation in these two species. Comparative studies of the peptide substrate specificities of hNmt and Nmt1p using a panel of 12 octapeptides revealed distinct differences in their tolerance for amino acid substitutions at positions 3, 4, 7, and 8 of parental peptides derived from the amino-terminal sequences of known N-myristoyl proteins. This finding contrasts with our recent observation that the acyl-CoA substrate specificities of hNmt and Nmt1p are highly conserved and suggests that these differences in peptide recognition provide an opportunity to develop species-specific enzyme inhibitors. PMID- 8486725 TI - Partitioning between N-dealkylation and N-oxygenation in the oxidation of N,N dialkylarylamines catalyzed by cytochrome P450 2B1. AB - Aminium radicals have been proposed as intermediates in amine N-dealkylations and N-oxygenations catalyzed by cytochrome P450 (P450) and some other enzymes. P450s can form some N-oxides and hydroxylamines but these are not favored whenever N dealkylation is possible. However, if a paradigm involving 1-electron oxidation is valid, then some finite level of partitioning of aminium radicals between N oxygenation and N-dealkylation might be expected in all cases. Methods were developed for the selective and sensitive measurement of N,N-dialkylaniline N oxides using high performance liquid chromatography, radiochromatography, and TiCl3 reduction. These N-oxides were relatively stable in the presence of P450 2B1. In the presence of NADPH and NADPH-P450 reductase some reduction to N,N dialkylamines occurred, along with N-dealkylation (to monoalkylanilines); there was also slow N-dealkylation in the absence of NADPH, which is interpreted in terms of homolytic scission of the N-O bond; N,N-dialkylanilines were not formed nor did the N-oxides support other oxygenation reactions. P450 2B1 (with its reductase and NADPH) formed N-oxides at low rates from several N,N-dialkylaniline derivatives, including N,N-dimethylaniline, N,N-diethylaniline, N-ethyl-N methylaniline, 4-methyl-N,N-dimethylaniline, 4-cyano-N,N-dimethylaniline, N phenylpyrrolidine, and N,N-dimethyl-2-aminofluorene. The ratio of N dealkylation:N-oxygenation varied from 1020 to 6 in this series. These results are consistent with the view that aminium radicals are a branch point in N oxygenation and N-dealkylation reactions catalyzed by metalloproteins, although some alternate explanations cannot be ruled out. While N-dealkylation is the dominant process in all of the P450-catalyzed amine oxidations, there should be a finite partition ratio between these reactions depending upon the particular enzyme and substrate. The N-oxygenation reaction is probably more complex than a direct radical recombination event and is postulated to involve one or more intermediates. PMID- 8486724 TI - Phytanic acid alpha-oxidation. Differential subcellular localization in rat and human tissues and its inhibition by nycodenz. AB - The subcellular site of oxidation of [1-14C]phytanic acid to pristanic acid and CO2 was examined by measurement of the release of 14CO2 in different organelles from human and rat tissues prepared by isopycnic density gradient centrifugation in Nycodenz. The activity of phytanic acid oxidation in human tissues (liver and cultured skin fibroblasts) paralleled that of the peroxisomal marker catalase. We also observed that Nycodenz (commonly used gradient material for isolation of subcellular organelles) has a strong inhibitory effect on the alpha-oxidation of phytanic acid. This inhibition is reversible and can be decreased or eliminated by dialysis of isolated organelles against isotonic solution. The dialysis of endoplasmic reticulum, mitochondrial, and peroxisomal fractions from human liver and cultured skin fibroblasts for 2 h against isotonic solution increased the specific activity of phytanic acid oxidation by 1.3-, 1.3-, and 5-21-fold, respectively, after removal of Nycodenz as compared with nondialyzed samples. After dialysis, the rate of oxidation of phytanic acid in peroxisomes from human liver and cultured skin fibroblasts was 4-26 times higher than that in mitochondria and 43-130 times than that in the endoplasmic reticulum, suggesting that, in human tissues, phytanic acid is oxidized to pristanic acid in peroxisomes. On the other hand, the oxidation of phytanic acid in rat liver paralleled the distribution of the mitochondrial marker cytochrome-c oxidase. The 18-fold higher rate of oxidation in dialyzed mitochondria (198.6 +/- 4.20 pmol/h/mg of protein) than in peroxisomes (11.0 +/- 0.5 pmol/h/mg of protein) demonstrates that, in rodents, phytanic acid is oxidized in mitochondria. 2-[5-(4 Chlorophenyl)pentyl]oxiran-2-carboxylic acid, an inhibitor of carnitine palmitoyltransferase I and mitochondrial fatty acid oxidation, inhibits the oxidation of phytanic acid in rat tissues (liver and cultured skin fibroblasts), whereas it has no effect on the oxidation of phytanic acid in human tissues (liver and cultured skin fibroblasts). The higher specific activity of phytanic acid oxidation in peroxisomes compared with that in mitochondria and the endoplasmic reticulum from human tissues and the inhibition of phytanic acid oxidation by 2-[5-(4-chlorophenyl)pentyl]oxiran-2-carboxylic acid in rat tissues (but not human tissues) demonstrate clearly that, in human tissues, phytanic acid is predominantly oxidized in peroxisomes. PMID- 8486726 TI - Role of endothelium in the responses to noradrenaline in normal and sensitized guinea-pig aorta. AB - 1. The pharmacological reactivity of sensitized blood vessels has been less studied than that of the airways. Aorta rings were obtained from normal (non sensitized) and actively sensitized guinea-pigs, and prepared for isometric recording of tension changes. 2. Noradrenaline (10 nM-0.1 mM), histamine (0.1 microM-0.1 mM) and KCl (10-100 mM) produced concentration-related contractions of normal tissues. Removal of endothelium resulted in a marked leftward and upward shift of the concentration-response curve for noradrenaline but it did not alter histamine- or KCl-induced responses. Pretreatment with L-NG-nitroarginine (L NOARG, 30 microM), haemoglobin (5 microM) or ibuprofen (10 microM) enhanced noradrenaline-induced responses without affecting those to histamine or KCl. 3. Removal of endothelium or pretreatment with L-NOARG or ibuprofen did not alter agonist-induced responses in sensitized tissues. Acetylcholine (1 microM)-induced relaxation of the contraction produced by noradrenaline (1 microM) in intact rings was diminished in sensitized compared to normal tissues. 4. Neuronal uptake and release of [3H]-noradrenaline did not differ in normal and sensitized tissues. 5. Loss of the modulatory role of endothelium and other mechanisms may be involved in the hyperreactivity of sensitized guinea-pig aorta. PMID- 8486727 TI - Mechanisms involved in the increased vascular resistance in hypertension. PMID- 8486728 TI - Relationship between local myocardial adenylyl cyclase activity and local coronary blood flow in the dog heart. AB - 1. This study tested the hypothesis that heterogeneity of myocardial adenylyl cyclase activity exists and contributes to the heterogeneity of blood flow in canine myocardium, in which flow varies in different areas at any one moment or in a single area at different times. 2. Tissue adenylyl cyclase activity was measured simultaneously with coronary blood flow in the left ventricle of eight anaesthetized open-chest dogs. Coronary flow was measured using radioactive microspheres under control conditions and after sympathetic stimulation. The ventricle was cut into 15 subepicardial and 15 subendocardial sections in which both flow and adenylyl cyclase (basal and forskolin-stimulated) activity were assayed. 3. Control coronary flow was 73.1 +/- 19.9 ml min-1 100 g-1 and ansa subclavia nerve stimulation increased flow to 93.2 +/- 26.1. Baseline adenylyl cyclase activity averaged 51.9 +/- 38.8 pmol min-1 mg protein-1, while forskolin stimulated activity was 588.2 +/- 393.6. Method variability was approximately 10% of the mean, much less than the biological variability of 70%. 4. Regression analysis of control flow vs baseline adenylyl cyclase activity produced the equation: flow = 0.25 (Adenylyl Cyclase)+60.6, (r = 0.47, P < 0.0001). The equation for stimulated flow vs stimulated adenylyl cyclase was: flow = 0.03 (Adenylyl Cyclase)+73.1, (r = 0.51, P < 0.0001). 5. Thus, significant heterogeneity of tissue adenylyl cyclase activity existed in the heart. There was also a direct linear relationship between adenylyl cyclase activity and coronary flow heterogeneity in canine left ventricle. PMID- 8486729 TI - Nomenclature of the desmosomal cadherins. PMID- 8486730 TI - The molecular organization of tight junctions. PMID- 8486731 TI - The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. AB - We previously identified a 220-kD constitutive protein of the plasma membrane undercoat which colocalizes at the immunofluorescence microscopic level with cadherins and occurs not only in epithelial M., S. Yonemura, A. Nagafuchi, Sa. Tsukita, and Sh. Tsukita. 1991. J. Cell Biol. 115:1449-1462). To clarify the nature and possible functions of this protein, we cloned its full-length cDNA and sequenced it. Unexpectedly, we found mouse 220-kD protein to be highly homologous to rat protein ZO-1, only a part of which had been already sequenced. This relationship was confirmed by immunoblotting with anti-ZO-1 antibody. As protein ZO-1 was originally identified as a component exclusively underlying tight junctions in epithelial cells, where cadherins are not believed to be localized, we analyzed the distribution of cadherins and the 220-kD protein by ultrathin cryosection immunoelectron microscopy. We found that in non-epithelial cells lacking tight junctions cadherins and the 220-kD protein colocalize, whereas in epithelial cells (e.g., intestinal epithelial cells) bearing well-developed tight junctions cadherins and the 220-kD protein are clearly segregated into adherens and tight junctions, respectively. Interestingly, in epithelial cells such as hepatocytes, which tight junctions are not so well developed, the 220-kD protein is detected not only in the tight junction zone but also at adherens junctions. Furthermore, we show in mouse L cells transfected with cDNAs encoding N-, P-, E cadherins that cadherins interact directly or indirectly with the 220-kD protein. Possible functions of the 220-kD protein (ZO-1) are discussed with special reference to the molecular mechanism for adherens and tight junction formation. PMID- 8486732 TI - NDC10: a gene involved in chromosome segregation in Saccharomyces cerevisiae. AB - A mutant, ndc10-1, was isolated by anti-tubulin staining of temperature-sensitive mutant banks of budding yeast. ndc10-1 has a defect chromosome segregation since chromosomes remains at one pole of the anaphase spindle. This produces one polyploid cell and one aploid cell, each containing a spindle pole body (SPD. NDC10 was cloned and sequenced and is identical to CBF2 (Jiang, W., J. Lechnermn and J. Carbon. 1993. J. Cell Biol. 121:513) which is the 110-kD component of a centromere DNA binding complex (Lechner, J., and J. Carbon. 1991. Cell. 61:717 725). NDC10 is an essential gene. Antibodies to Ndc10p labeled the SPB region in nearly all the cells examined including nonmitotic cells. In some cells with short spindles which may be in metaphase, staining was also observed along the spindle. The staining pattern and the phenotype of ndc10-1 are consistent with Cbf2p/Ndc10p being a kinetochore protein, and provide in vivo evidence for its role in the attachment of chromosomes to the spindle. PMID- 8486733 TI - Isolation and characterization of a gene (CBF2) specifying a protein component of the budding yeast kinetochore. AB - We have cloned and determined the nucleotide sequence of the gene (CBF2) specifying the large (110 kD) subunit of the 240-kD multisubunit yeast centromere binding factor CBF3, which binds selectively in vitro to yeast centromere DNA and contains a minus end-directed microtubule motor activity. The deduced amino acid sequence of CBF2p shows no sequence homologies with known molecular motors, although a consensus nucleotide binding site is present. The CBF2 gene is essential for viability of yeast and is identical to NDC10, in which a conditional mutation leads to a defect in chromosome segregation (Goh, P.-Y., and J. V. Kilmartin, in this issue of The Journal of Cell Biology). The combined in vitro and in vivo evidence indicate that CBF2p is a key component of the budding yeast kinetochore. PMID- 8486734 TI - Assembly of vaccinia virus: role of the intermediate compartment between the endoplasmic reticulum and the Golgi stacks. AB - Vaccinia virus, the prototype of the Poxviridae, is a large DNA virus which replicates in the cytoplasm of the host cell. The assembly pathway of vaccinia virus displays several unique features, such as the production of two structurally distinct, infectious forms. One of these, termed intracellular naked virus (INV), remains cells associated while the other, termed extracellular enveloped virus (EEV), is released from the cell. In addition, it has long been believed that INVs acquire their lipid envelopes by a unique example of de novo membrane biogenesis. To examine the structure and assembly of vaccinia virus we have used immunoelectron microscopy using antibodies to proteins of different subcellular compartments as well as a phospholipid analysis of purified INV and EEV. Our data are not consistent with the de novo model of viral membrane synthesis but rather argue that the vaccinia virus DNA becomes enwrapped by a membrane cisterna derived from the intermediate compartment between the ER and the Golgi stacks, thus acquiring two membranes in one step. Phospholipid analysis of purified INV supports its derivation from an early biosynthetic compartment. This unique assembly process is repeated once more when the INV becomes enwrapped by an additional membrane cisterna, in agreement with earlier reports. The available data suggest that after fusion between the outer envelope and the plasma membrane, mature EEV is released from the cell. PMID- 8486735 TI - Membrane flux through the pore formed by a fusogenic viral envelope protein during cell fusion. AB - We have investigated the mechanism of cell fusion mediated by HA, the fusogenic hemagglutinin of the Influenza viral envelope. Single erythrocytes (RBCs) were attached to fibroblasts expressing the HA on their cell surface, and fusion of the paired cells was triggered by rapid acidification. The RBC membrane was stained with fluorescent lipid, and the fusion-induced escape of lipid into the fibroblast was observed by quantitative image analysis. At the same time, the formation of an aqueous connection (i.e., the fusion pore) between the two cells was monitored electrically. Within minutes after acidification, an electrical conductance between the two cells appeared abruptly as the fusion pore opened, and then increased gradually as the pore dilated. Later, fluorescent lipid diffused into the fibroblast, approaching equilibrium over the next 5-20 min. No lipid flux was seen while the pore conductance remained 0.5 nS or less. Evidently lipid flux requires a threshold pore size. Our finding suggests that the smallest and earliest fusion pores are surrounded by a ring of protein. A fusion pore expands by breaking this ring and recruiting lipid into its circumference. PMID- 8486737 TI - A novel cytoskeletal structure involved in purse string wound closure and cell polarity maintenance. AB - The process of wound repair in monolayers of the intestinal epithelial cell line, Caco-2BBe, was analyzed by a combination of time-lapse differential interference contrast (DIC) video and immunofluorescence microscopy, and laser scanning confocal immunofluorescence microscopy (LSCIM). DIC video analysis revealed that stab wounds made in Caco-2BBe monolayers healed by two distinct processes: (a) Extension of lamellipodia into the wounds; and (b) Purse string closure of the wound by distinct arcs or rings formed by cells bordering the wound. The arcs and rings which effected purse string closure appeared sharp and sheer in DIC, spanned between two and eight individual cells along the wound border, and contracted in a concerted fashion. Immunofluorescence analysis of the wounds demonstrated that the arcs and rings contained striking accumulations of actin filaments, myosin-II, villin, and tropomyosin. In contrast, arcs and rings contained no apparent enrichment of microtubules, brush border myosin-I immunogens, or myosin-V. LSCIM analysis confirmed the localization of actin filaments, myosin-II, villin, and tropomyosin in arcs and rings at wound borders. ZO-1 (a tight junction protein), also accumulated in arcs and rings around wounds, despite the fact that cell-cell contacts are absent at wound borders. Sucrase-isomaltase, an apically-localized integral membrane protein, maintained an apical localization in cells where arcs or rings were formed, but was found in lamellipodia extending into wounds in cells where arcs failed to form. Time course, LSCIM quantification of actin, myosin II, and ZO-1 revealed that accumulation of these proteins within arcs and rings at the wound edge began within 5 minutes and peaked within 30-60 minutes of wounding. Actin filaments, myosin-II, and ZO-1 achieved 10-, 3-, and 4-fold enrichments, respectively, relative to cell edges which did not border wounds. The results demonstrate that wounded Caco-2BBe monolayers assemble a novel cytoskeletal structure at the borders of wounds. The results further suggest that this structure plays at least two roles in wound repair; first, mediation of concerted, purse string movement of cells into the area of the wound and second, maintenance of apical/basolateral polarity in cells which border the wound. PMID- 8486736 TI - Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization. AB - The rab subfamily of small GTPases has been demonstrated to play an important role in the regulation of membrane traffic in eukaryotic cells. Compared with nonpolarized cells, epithelial cells have distinct apical and basolateral transport pathways which need to be separately regulated. This raises the question whether epithelial cells require specific rab proteins. However, all rab proteins identified so far were found to be equally expressed in polarized and nonpolarized cells. Here we report the identification of rab17, the first epithelial cell-specific small GTPase. Northern blot analysis on various mouse organs, revealed that the rab17 mRNA is present in kidney, liver, and intestine but not in organs lacking epithelial cells nor in fibroblasts. To determine whether rab17 is specific for epithelial cells we studied its expression in the developing kidney. We found that rab17 is absent from the mesenchymal precursors but is induced upon their differentiation into epithelial cells. In situ hybridization studies on the embryonic kidney and intestine revealed that rab17 is restricted to epithelial cells. By immunofluorescence and immunoelectron microscopy on kidney sections, rab17 was localized to the basolateral plasma membrane and to apical tubules. Rab proteins associated with two distinct compartments have been found to regulate transport between them. Therefore, our data suggest that rab17 might be involved in transcellular transport. PMID- 8486738 TI - Flightin, a novel myofibrillar protein of Drosophila stretch-activated muscles. AB - The indirect flight muscles of Drosophila are adapted for rapid oscillatory movements which depend on properties of the contractile apparatus itself. Flight muscles are stretch activated and the frequency of contraction in these muscles is independent of the rate of nerve impulses. Little is known about the molecular basis of these adaptations. We now report a novel protein that is found only in flight muscles and has, therefore, been named flightin. Although we detect only one gene (in polytene region 76D) for flightin, this protein has several isoforms (relative gel mobilities, 27-30 kD; pIs, 4.6-6.0). These isoforms appear to be created by posttranslational modifications. A subset of these isoforms is absent in newly emerged adults but appears when the adult develops the ability to fly. In intact muscles flightin is associated with the A band of the sarcomere, where evidence suggests it interacts with the myosin filaments. Computer database searches do not reveal extensive similarity to any known protein. However, the NH2-terminal 12 residues show similarity to the NH2-terminal sequence of actin, a region that interacts with myosin. These features suggest a role for flightin in the regulation of contraction, possibly by modulating actin-myosin interaction. PMID- 8486739 TI - The Ca(2+)-binding domains in non-muscle type alpha-actinin: biochemical and genetic analysis. AB - Dictyostelium alpha-actinin is a Ca(2+)-regulated F-actin cross-linking protein. To test the inhibitory function of the two EF hands, point mutations were introduced into either one or both Ca(2+)-binding sites. After mutations, the two EF hands were distinguishable with respect to their regulatory activities. Inactivation of EF hand I abolished completely the F-actin cross-linking activity of Dictyostelium discoideum alpha-actinin but Ca2+ binding by EF hand II was still observed in a 45Ca2+ overlay assay. In contrast, after mutation of EF hand II the molecule was still active and inhibited by Ca2+; however, approximately 500-fold more Ca2+ was necessary for inhibition and 45Ca2+ binding could not be detected in the overlay assay. These data indicate that EF hand I has a low affinity for Ca2+ and EF hand II a high affinity, implying a regulatory function of EF hand I in the inhibition of F-actin cross-linking activity. Biochemical data is presented which allows us to distinguish two functions of the EF hand domains in D. discoideum alpha-actinin: (a) at the level of the EF-hands, the Ca(2+)-binding affinity of EF hand I was increased by EF hand II in a cooperative manner, and (b) at the level of the two subunits, the EF hands acted as an on/off switch for actin-binding in the neighboring subunit. To corroborate in vitro observations in an in vivo system we tried to rescue the abnormal phenotype of a mutant (Witke, W., M. Schleicher, A. A. Noegel. 1992. Cell. 68:53-62) by introducing the mutated alpha-actinin cDNAs. In agreement with the biochemical data, only the molecule modified in EF hand II could rescue the abnormal phenotype. Considering the fact that the active construct is "always on" because it requires nonphysiological, high Ca2+ concentrations for inactivation, it is interesting to note that an unregulated alpha-actinin was able to rescue the mutant phenotype. PMID- 8486740 TI - Expression of plectin mutant cDNA in cultured cells indicates a role of COOH terminal domain in intermediate filament association. AB - Plectin is an intermediate filament (IF) binding protein of exceptionally large size. Its molecular structure, revealed by EM and predicted by its sequence, indicates an NH2-terminal globular domain, a long rodlike central domain, and a globular COOH-terminal domain containing six highly homologous repeat regions. To examine the role of the various domains in mediating plectin's interaction with IFs, we have constructed rat cDNAs encoding truncated plectin mutants under the control of the SV-40 promoter. Mutant proteins expressed in mammalian COS and PtK2 cells could be distinguished from endogenous wild type plectin by virtue of a short carboxy-terminal antigenic peptide (P tag). As shown by conventional and confocal immunofluorescence microscopy, the transient expression of plectin mutants containing all six or the last four of the repeat regions of the COOH terminus, or the COOH-terminus and the rod, associated with IF networks of both the vimentin and the cytokeratin type and eventually caused their collapse into perinuclear aggregates. Similar effects were observed upon expression of a protein encoded by a full length cDNA construct. Microtubules and microfilaments were unaffected. Unexpectedly, mutants containing the rod without any of the COOH terminal repeats, accumulated almost exclusively within the nuclei of cells. When the rod was extended by the first one and a half of the COOH-terminal repeats, mutant proteins showed a partial cytoplasmic distribution, although association with intermediate filaments was not observed. Nuclear and diffuse cytoplasmic distribution was also observed upon expression of the NH2-terminal domain without rod. These results indicate that sequences located roughly within the last two thirds of the globular COOH-terminus are indispensable for association of plectin with intermediate filaments in living cells. PMID- 8486742 TI - Mouse notch: expression in hair follicles correlates with cell fate determination. AB - Many vertebrate tissues, including skin, are known to develop as a consequence of epithelial-mesenchymal interactions. Much less is known about the role of cell cell interaction within the epithelial or the mesenchymal compartments in morphogenesis. To investigate cell-cell interactions during skin development, and the potential role of the Notch homolog in this process, we cloned the mouse homolog of Notch (mNotch) and studied its expression pattern, starting as early as mesoderm formation. The novel application of double-labeled in situ hybridization in vertebrates allowed high resolution analysis to follow the fate of mNotch expressing cells directly. In comparison with the distribution of Id mRNA, analysis confirmed that in the hair follicle high levels of mNotch are expressed exclusively in the epithelial compartment. Hair follicle matrix cells start expressing mNotch as different cell types become distinguishable in the developing follicle. mNotch mRNA expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level mNotch expression are in transition from mitotic precursors to several discreet, differentiating cell types. Our observations point out that both in time (during development) and in space (by being removed one cell layer from the dermal papilla) mNotch expression is clearly separated from the inductive interactions. This is a novel finding and suggests that mNotch is important for follicular differentiation and possibly cell fate selection within the follicle. PMID- 8486741 TI - Essential roles for calcium and calmodulin in G2/M progression in Aspergillus nidulans. AB - nimT encodes a protein in Aspergillus nidulans that is required for tyrosine dephosphorylation of p34cdc2 and has a strong homology to cdc25-type proteins. Conditional mutation of nimT (nimT23 mutation) arrests cells in G2 at the restrictive temperature. After release of the temperature-sensitive nimT23 block, p34cdc2 undergoes tyrosine dephosphorylation and we showed that as cells entered mitosis, a rapid increase in calmodulin was observed. The increase in calmodulin and progression into mitosis were prevented by reducing extracellular Ca2+ levels to 2 nM. The calmodulin gene of a nimT23-containing strain was replaced with a hybrid gene in which calmodulin transcription was regulated by the alcA promoter (AlcCaM/T23). This allowed experimental manipulation of the level of intracellular calmodulin by the carbon source in the medium. When either extracellular Ca2+ or intracellular calmodulin levels were reduced at the nimT23 G2 arrest point, p34cdc2 remained tyrosine phosphorylated but the mitotic NIMA kinase encoded by nimA was not activated. Release of the temperature sensitive nimT23 arrest when either extracellular Ca2+ or calmodulin concentrations were low blocked tyrosine dephosphorylation of p34cdc2, activation of NIMA and progression of cells into mitosis. However, reduced levels of either Ca2+ or calmodulin had no effect on the increase in histone H1 kinase activity associated with p13 beads or the degree of phosphorylation of the majority of MPM-2-reacting proteins following release of the nimT23 mutation. These results demonstrate that both Ca2+ and calmodulin are important for progression into mitosis from the nimT23 arrest point in a pathway involving activation of both NIMA and p34cdc2 protein kinases. PMID- 8486744 TI - Column liquid chromatographic determination of flavanone glycosides in Citrus. Application to grapefruit and sour orange juice adulterations. AB - Six flavone glycosides were separated by HPLC using RP-18 with a quaternary mobile phase mixture [water-acetonitrile-tetrahydrofuran-acetic acid (80:16:3:1, v/v)]. This procedure was applied to the separation and determination of the most important flavanone glycosides contained in pure grapefruit and sour orange juices and mixtures. This method can be used for quality control of industrial concentrates and juices. PMID- 8486743 TI - Involvement of ras p21 in neurotrophin-induced response of sensory, but not sympathetic neurons. AB - Little is known about the signal transduction mechanisms involved in the response to neurotrophins and other neurotrophic factors in neurons, beyond the activation of the tyrosine kinase activity of the neurotrophin receptors belonging to the trk family. We have previously shown that the introduction of the oncogene product ras p21 into the cytoplasm of chick embryonic neurons can reproduce the survival and neurite-outgrowth promoting effects of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and of ciliary neurotrophic factor (CNTF). To assess the potential signal-transducing role of endogenous ras p21, we introduced function-blocking anti-ras antibodies or their Fab fragments into cultured chick embryonic neurons. The BDNF-induced neurite outgrowth in E12 nodose ganglion neurons was reduced to below control levels, and the NGF-induced survival of E9 dorsal root ganglion (DRG) neurons was inhibited in a specific and dose-dependent fashion. Both effects could be reversed by saturating the epitope-binding sites with biologically inactive ras p21 before microinjection. Surprisingly, ras p21 did not promote the survival of NGF dependent E12 chick sympathetic neurons, and the NGF-induced survival in these cells was not inhibited by the Fab-fragments. The survival effect of CNTF on ras responsive ciliary neurons could not be blocked by anti-ras Fab fragments. These results indicate an involvement of ras p21 in the signal transduction of neurotrophic factors in sensory, but not sympathetic or ciliary neurons, pointing to the existence of different signaling pathways not only in CNTF-responsive, but also in neurotrophin-responsive neuronal populations. PMID- 8486745 TI - Recognition of enantiomers by Chirasil-Val and oligopeptide analogues as studied by gas-phase calorimetry and 1H NMR spectroscopy in solution. AB - A series of oligopeptides, L-Valn-NHtBu (n = 1-4), were linked to poly(beta methyl)siloxy-alpha-methylpropanoic acid copolymer; the resulting chirally modified polydimethylsiloxanes were used for the resolution of enantiomers by gas chromatography. Chiral recognition proved most effective for n = 1 (known as Chirasil-Val), as judged from the resolution factors (alpha) and the thermodynamic parameters delta delta H, delta delta S and chi = delta delta H/delta H', where delta H' = delta HChir -delta HSE30. Likewise, 1H NMR spectroscopy in carbon tetrachloride solution revealed a maximum chemical shift non-equivalence of the amide N-H signal of racemic N-TFA-amino acid methyl esters on addition of the chiral polymer, for n = 1. From circular dichroism spectroscopy of L-Valn-NH'Bu (n = 2, 3, 4 and 6) and polyoxyethylene-bound pivaloyl-L-Valn-Gly-NH-POE3000 (n = 2-8), it is concluded that the peptide moiety of the stationary phase mostly adopts the unfavourable random coil conformation, whereas the beta-sheet structure was only partially found and only for n > or = 6. PMID- 8486746 TI - Effect of stationary phase solvation on shape selectivity in reversed-phase high performance liquid chromatography. AB - The effect of stationary phase solvation on reversed-phase chromatographic shape selectivity has been investigated using n-hexanol as an additive to methanol water mobile phases. A wide range of mobile phase compositions was evaluated to normalize for solvent strength selectivity differences. Monomeric C18 stationary phases of both high and low bonding density were synthesized and used to correlate selectivity changes caused by stationary phase ordering with those seen by the addition of n-hexanol. The temperature dependence of retention and selectivity was also investigated using Van 't Hoff plots, which provided insight into the nature of selectivity behavior for estrogens and polyaromatic hydrocarbons. The results showed that using n-hexanol as a mobile phase additive did not provide higher shape selectivity, suggesting that changes in the solvation of the stationary phase did not impart a significant change in the level of surface ordering or morphology. However, n-hexanol did impart solvent selectivity changes in the separation of estrogen diastereomers that could prove useful in future methods development schemes. PMID- 8486747 TI - Characterization of N-ethoxycarbonyl ethyl esters of amino acids by mass spectrometry. AB - Derivatization of amino acids by using ethyl chloroformate-ethanol-pyridine provides volatile products, N-ethoxycarbonyl amino acid ethyl esters (ECEEs), which are easily amenable to GC or GC-MS analysis. MS behavior of these compounds under electron-impact has been studied. The fragments observed in the spectra facilitate recognition of commonly occurring protein amino acids and characterization of unknown analogues. PMID- 8486748 TI - Separation of cardiac glycosides by micellar electrokinetic capillary electrophoresis. AB - The separation of mixtures of primary and secondary cardiac glycosides by micellar electrokinetic capillary electrophoresis modified by cyclodextrins, urea and sodium cholate proved to be suitable for the determination of these hydrophobic compounds. It was possible to distinguish the two anomeric cardenolides glucodigifucoside and glucodigiglucomethyloside with all three buffer systems. Electropherograms of crude plant cell extracts from Digitalis lanata were obtained with this method. PMID- 8486749 TI - The 1990 Montana initiative to increase cigarette taxes: lessons for other states and localities. AB - In November 1990, voters in Montana defeated an initiative that would have increased the state's excise tax on a pack of cigarettes by 25 cents. The increased revenues were intended for tobacco education and research. Opponents of the measure, primarily tobacco companies, outspent proponents by more than 35 to 1. Their primary themes were opposition to new taxes and to a larger state bureaucracy. Based on the results of initiative campaigns in Montana and California, taxation initiatives are more likely to succeed if guidance is sought from leaders of similar campaigns in other states, tobacco control coalitions are built and funding secured early, and polling conducted before initiative measures are finalized. Other requirements for success include careful wording of the initiative, strong leadership, consideration of a paid petition drive, effective use of the news media, anticipating opposition arguments, and emphasizing the benefits of the tax increase in the campaign. PMID- 8486750 TI - Longitudinal observations on a selected group of local health departments: a preliminary report. AB - A study is in progress to document changes in selected public health departments over the past decade and to use those observations for proposing an assessment protocol that may be helpful in measuring progress toward achieving one of the Health Objectives for the Nation for the Year 2000. Objective no. 8.14 reads: "Increase to at least 90 percent the proportion of people served by a local health department that is effectively carrying out the core functions of public health." The study re-surveys a group of 14 departments that were the subjects of intensive case studies between 1979 and 1981. Some preliminary observations from follow-up study of these departments in 1992 include: growth in budget and staff and even larger growth in pressure for services, especially for personal health care; reorganization that splits away some programs of comprehensive ambulatory care and responsibility for public hospitals, while increasing the aggregation of human service agencies, including public health, under locally organized umbrella agencies; increase in preventive, screening, and categorical programs under public health sponsorship; drastic change in patterns of financing, featuring nearly total loss of direct federal grants, and increase in fee income; increase in the number of community and migrant health centers in the public health jurisdictions under study; diminished collaborative interaction with private practitioners; and continued close collaboration between health departments and community health centers in several communities. The implications of these changes are discussed. Subsequent reports will be based on efforts to measure the impact of specific events of the 1980s on public health performance, and will describe experience with a community-based surveillance approach for assessing public health performance. PMID- 8486751 TI - The evolution, impact and significance of the healthy cities/healthy communities movement. AB - The Healthy Cities movement, or Healthy Communities as it is known in some parts of the world, has grown rapidly since it was launched in 1986. In addition to the 35 cities formally associated with the WHO Europe project, there are now 18 national networks and hundreds of towns and cities actively involved in Europe, North America, and, increasingly, the developing world. This article reviews the concept, its evolution and current practice, considers some of the problems in applying the concept, and speculates on its potential future development. PMID- 8486752 TI - Exporting asbestos: disease and policy in the developing world. AB - The health effects of asbestos are well known, with lung cancer, mesothelioma and asbestosis recognized as the most common causes of mortality and morbidity among exposed populations. Recognition of these hazards coupled with an explosion of litigation against asbestos manufacturers brought by injured workers has resulted in declining markets for this commodity in the U.S. and other Western democracies. With Western markets for asbestos decreasing, the developing world has become the target of asbestos exporters in an attempt to revitalize an industry in decline. This paper discusses the trends in worldwide asbestos markets over the last two decades and the serious health implications of policies directed at establishing viable markets for this commodity in developing nations. PMID- 8486753 TI - Persisting health inequalities: social class differentials in illness in the Scandinavian countries. AB - Finland, Norway and Sweden are highly developed welfare states with a long tradition of egalitarian health and welfare policies. This article analyzes social class differentials in self-reported limiting long-standing illness among men and women in these countries. The data consisted of nation-wide Level of Living Surveys made in 1986-87 in Finland (N = 11,783), Norway (N = 4,211) and Sweden (N = 4,699). Women reported both long-standing illness and limiting long standing illness slightly more often than men. The prevalence of limiting long standing illness was lower in Sweden than in Finland and Norway. In all countries blue-collar workers reported ill-health more often than white-collar employees. The prevalence of self-reported limiting long-standing illness among Swedish upper white-collar workers was very low and that among Finnish farmers very high. Skilled female workers showed the worst health whereas Swedish upper class men showed the best health. The reasons for these social inequalities, and their implications for social policy, are discussed. PMID- 8486754 TI - Socioeconomic differences in fetal and infant mortality in Scandinavia. AB - This study demonstrates that socioeconomic differences do exist in all three Scandinavian countries, and these differences have implications for perinatal and infant survival. Using parental education as a proxy for socioeconomic conditions, the association with perinatal survival seems to be stronger in Denmark and Norway than in Sweden. For postneonatal mortality the association is equally strong in the three countries. Data from one of the countries (Norway) demonstrates the joint importance of parental education, and the association with paternal education is equally strong as that with maternal education. If father and mother have the lowest level of education, their offspring has 50 to 80% higher perinatal and infant mortality risks. These observations call for further research into the association between social variables and health in order to tease out causal relationships which might lead to future preventive actions. PMID- 8486755 TI - Free exchange of medical supplies, information, and personnel with Cuba. American Public Health Association. PMID- 8486756 TI - Regional conflicts and their threat to world peace. Coordinating Committee, World Council of Health Worker Organizations for Social Well-Being, Health and Peace. PMID- 8486757 TI - AMP and microamps: neutrophil-derived chloride secretagogue identified. PMID- 8486758 TI - Pulmonary neuroendocrine cells and lung development: dim outlines emerge. PMID- 8486759 TI - Importance of factor Xa in determining the procoagulant activity of whole-blood clots. AB - The binding of thrombin to fibrin is thought to be an important mechanism by which thrombi exhibit procoagulant activity; however, the extent to which other procoagulants are associated with thrombi has not been previously defined. This study was designed to determine whether clotting factors other than thrombin are bound to whole-blood clots and can thereby contribute to significant procoagulant activity. Clots formed in vitro from human blood exhibited minimal thrombin activity when incubated in plasma depleted of vitamin K-dependent factors by barium-citrate adsorption, as indicated by increases in the concentration of fibrinopeptide A (FPA), a marker of fibrin formation, to 72 nM after 30 min. Incubation of clots in barium-absorbed plasma repleted with 0.9 microM human prothrombin under the same conditions resulted in marked increases in the concentration of FPA (> 1,000 nM) and clotting by 30 min. The increases in FPA were attributable to activation of the added prothrombin by clot-associated Factor Xa, judging from concomitant increases in the concentration of prothrombin fragment 1.2. Similar results were obtained with thrombi induced in the axillary arteries of dogs by vascular injury and incubated with plasma in vitro. Activation of prothrombin was inhibited in a dose-dependent manner by tick anticoagulant peptide, a direct inhibitor of Factor Xa, at concentrations of 0.5 5.0 microM. Clot-associated Factor Xa activity was resistant to inhibition by anti-thrombin III, judging from the lack of inhibition of prothrombin activation during incubation of clots in plasma containing heparin pentasaccharide, an anti thrombin III-mediated inhibitor of Factor Xa. Thus, the activity of Factor Xa appears to be an important determinant of the procoagulant activity of whole blood clots and arterial thrombi, and is resistant to inhibition by anti-thrombin III-dependent inhibitors. PMID- 8486760 TI - Carbamyl phosphate synthetase I deficiency. One base substitution in an exon of the CPS I gene causes a 9-basepair deletion due to aberrant splicing. AB - Carbamyl phosphate synthetase I (CPS I; EC6,3,4,16) is an autosomal recessive disorder characterized by hyperammonemia. We studied the molecular bases of CPS I deficiency in a newborn Japanese girl with consanguineous parents. Northern and Western blots revealed a marked decrease in CPS I mRNA and enzyme protein but with a size similar to that of the control, respectively. Sequencing of the patient's cDNA revealed a nine-nucleotide deletion at position 832-840. Sequencing analysis of the genomic DNA revealed a G to C transversion at position 840, the last nucleotide of an exon in the splice donor site. This substitution altered the consensus sequence of the splice donor site and the newly cryptical donor site in the exon caused the 9-bp in-frame deletion. This report seems to be the first complete definition of CPS I deficiency, at the molecular level. PMID- 8486761 TI - Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism. AB - BACKGROUND: Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients. METHODS: Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron emission tomography scan. RESULTS: Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis. CONCLUSIONS: Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle. PMID- 8486762 TI - Binding, internalization, and degradation of mannose-terminated glucocerebrosidase by macrophages. AB - Mannose-terminated glucocerebrosidase (alglucerase; Ceredase) was designed for enzyme replacement therapy in Gaucher disease to take advantage of mannose receptor-mediated endocytosis by macrophages. To provide a rational basis for designing enzyme replacement therapy protocols, we examined the in vitro binding, uptake, and degradation of alglucerase by murine and human macrophages. Both were found to have approximately 500,000 mannose-dependent receptors for alglucerase per cell with a Kd of 10(-7) M at 0 degrees C. In contrast, the number of binding sites for mannose-bovine serum albumin (mannose-BSA), the classical ligand for the mannose receptor, was only approximately 20,000 with a Kd of 10(-8) M. Alglucerase was also bound in a mannose-dependent manner by cells that lack the capacity to bind mannose-BSA, such as Cos-1 cells, endothelial cells, and peripheral blood monocytes. The fact that the binding of alglucerase by macrophages was mediated principally by a receptor distinct from the classical mannose receptor that binds mannose-BSA was confirmed by differential inhibitors, viz., alpha-methyl-glucoside, fucose, and mannose-BSA, and by its independence on Ca2+. Uptake of alglucerase by macrophages at 37 degrees C was concentration dependent and half maximal at 10(-6) M. However, at a concentration of 10(-7) M, only 0.5% of the added alglucerase was incorporated into macrophages and approximately 50% of the alglucerase taken up was quickly released into the medium. Endothelial cells also manifest mannose-dependent binding and uptake of alglucerase and may therefore account for a large proportion of the infused alglucerase. Our data suggest that only a small amount of the alglucerase administered is effectively delivered to macrophages and that a more efficiently targeted enzyme might have a marked therapeutic advantage over mannose-terminated glucocerebrosidase. PMID- 8486763 TI - Cell-cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture. AB - It is unclear whether signaling between endothelial cells and muscle cells within ventricular myocardium, known to be important during cardiac development, remains physiologically relevant in the adult heart. Also, the mechanisms regulating the synthesis and activation of locally acting autacoids such as endothelins, cytokines known to have potent effects on contractile function and gene expression in cardiac myocytes, are unknown, as their cells of origin within ventricular muscle. Microvascular endothelial cells isolated from ventricular tissue of adult rats do not express endothelins constitutively. However, the appearance of preproendothelin mRNA can be increased in cardiac microvascular endothelial cells by heterotypic primary culture with adult rat ventricular myocytes. Cell-cell contact, or at least close apposition, appears to be necessary to increase preproendothelin mRNA, as medium conditioned by ventricular myocytes alone was ineffective when applied to monocultures of microvascular endothelial cells. The level of TGF beta precursor mRNA is also markedly increased in microvascular endothelial cells in coculture and precedes the appearance of endothelin precursor transcripts. In coculture, TGF beta acts as an autocrine cytokine, increasing endothelin precursor mRNA and inhibiting the rate of microvascular endothelial cell proliferation. This regulation of endothelial cell phenotype in heterotypic primary cultures suggests that dynamic, reciprocal cell-cell signaling may also be occurring between microvascular endothelium and ventricular myocytes in vivo. PMID- 8486764 TI - Phospholipase D-modified low density lipoprotein is taken up by macrophages at increased rate. A possible role for phosphatidic acid. AB - Macrophage uptake of modified forms of LDL leads to cellular cholesterol accumulation. Upon incubation of LDL with phospholipase D (PLase D), a time- and enzyme dose-dependent production of phosphatidic acid (PA), paralleled by a rapid reduction in LDL phosphatidyl choline content (up to 65% within 15 min of incubation) was noted. No lipid peroxidation could be found in PLase D-modified LDL. Upon in vitro incubation of PLase D-LDL with copper ions, however, this modified LDL was substantially oxidized. The addition of 100 micrograms PA/ml to native LDL for the period of its in vitro oxidation resulted in a 63% elevation in the lipoprotein peroxides content. Incubation of PLase D-LDL with J-774A.1 macrophage-like cell line resulted in an increase in its cellular binding and degradation (up to 91 and 110%, respectively) in comparison with native LDL (via the LDL receptor). When PA was added to LDL before its incubation with the macrophages, a PA dose-dependent elevation in the cellular uptake of LDL (by up to twofold) was noted in comparison with LDL that was incubated without PA, suggesting that PA production in PLase D-LDL may be involved in the increased cellular uptake of PLase D-LDL. PLase D activity towards LDL was demonstrated in J-774A.1 macrophages. Human plasma was also shown to possess PLase D activity. Thus, PLase D modification of LDL may take place under certain pathological conditions and PLase D-LDL interaction with arterial wall macrophages can potentially lead to foam cell formation. PMID- 8486765 TI - Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a Ser172-->Cys mutation in the lipoprotein lipase gene. AB - Normal pregnancy is associated with a two- to threefold increase in plasma triglyceride levels, particularly in the third trimester, due both to the overproduction of VLDLs and to the possible suppression of lipoprotein lipase (LPL) activity. Numerous mutations in the human LPL gene causing complete LPL deficiency have been described, but naturally occurring mutations that result in defective LPL with partial activity have not yet been reported. Here we describe a 30-yr-old woman who was first diagnosed with LPL deficiency during pregnancy after she developed pancreatitis. Her plasma triglyceride levels remained mildly elevated at approximately 300 mg/dl (3.4 mmol/liter) after the first pregnancy but rose significantly after she became pregnant again (1800 to 2000 mg/dl) (20.2 to 22.5 mmol/liter). DNA sequence analysis of the LPL gene showed that the patient is homozygous for a Ser172-->Cys missense mutation in exon 5. In vitro mutagenesis revealed that the Ser172-->Cys mutation caused a mutant LPL protein that had residual activity higher than that seen in all eight other missense mutations in patients with LPL deficiency identified in our laboratory. We propose that some mutations in the LPL gene produce a defective LPL with partial activity, which usually leads to mild hypertriglyceridemia. PMID- 8486766 TI - Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport. AB - We have recently cloned, sequenced, and characterized a rat kidney cDNA (D2) that stimulates cystine as well as dibasic and neutral amino acid transport. In order to evaluate the role of this protein in human inherited diseases such as cystinuria, we have isolated a human D2 clone (D2H) by low stringency screening of a human kidney cDNA library using the radiolabeled D2 insert as a probe. The D2H cDNA is 2284 nucleotides long and encodes a 663 amino acid protein that is 80% identical to the rat D2 amino acid sequence and 86% to that of the rabbit homologue rBAT. Microinjection of in vitro transcribed D2H cRNA into Xenopus oocytes induced uptake of cystine as well as dibasic and neutral amino acids in a pattern similar to that of rat D2 and rabbit rBAT. Both neutral and dibasic amino acids inhibited the D2H-induced uptake of cystine. Northern blot analysis demonstrated that D2H, like D2 and rBAT, is expressed strongly in the kidney and intestine. Southern blot analysis of genomic DNA from a panel of mouse-human somatic cell hybrids showed that the human gene for D2H resides on chromosome 2. PMID- 8486767 TI - CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides. AB - Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. PMID- 8486768 TI - Terminal complement complex C5b-9 stimulates mitogenesis in 3T3 cells. AB - The membrane attack complex of complement (MAC) can induce reversible changes in cell membrane permeability resulting in significant but transient intracellular ionic changes in the absence of cell lysis. Because ion fluxes and cytosolic ionic changes are integral steps in the signaling cascade initiated when growth factors bind to their receptors, we hypothesized that the MAC-induced reversible changes in membrane permeability could stimulate cell proliferation. Using purified terminal complement components we have documented a mitogenic effect of the MAC for quiescent murine 3T3 cells. The MAC enhances the mitogenic effects of serum and PDGF, and also stimulates cell proliferation in the absence of other exogenous growth factors. MAC-induced mitogenesis represents a novel effect of the terminal complement complex that could contribute to focal tissue repair or pathological cell proliferation locally at sites of complement activation. PMID- 8486769 TI - Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies. AB - This study investigates the pathophysiology of mucormycosis caused by Rhizopus, which has been reported in 46 dialysis patients, while treated with deferoxamine (DFO). This drug aggravates mucormycosis, which we experimentally induced in guinea pigs and which lead to a shortened animal survival (P < or = 0.01). The drug's effect on Rhizopus is not mediated through the polymorphonuclear cells. Fe.DFO, the iron chelate of DFO, abolishes the fungistatic effect of serum on Rhizopus and increases the in vitro growth of the fungus (P < or = 0.0001). This effect is present at Fe.DFO concentrations > or = 0.01 microM, at which fungal uptake of radioiron from 55Fe.DFO is observed. A 1,000-fold higher concentration of iron citrate is required to achieve a similar rate of radioiron uptake and of in vitro growth stimulation as observed with Fe.DFO. These in vitro effects of Fe.DFO (1 microM) in serum on radioiron uptake and on growth stimulation are more striking for Rhizopus than for Aspergillus fumigatus and are practically absent for Candida albicans. For these three fungal species, the rates of radioiron uptake from 55Fe.DFO and of growth stimulation in the presence of Fe.DFO in serum are directly related (r = 0.886). These results underscore the major role of Fe.DFO in the pathogenesis of DFO-related mucormycosis. Pharmacokinetic changes in uremia lead to a prolonged accumulation of Fe.DFO after DFO administration, which helps explain the increased sensitivity of dialysis patients to DFO-related mucormycosis. PMID- 8486770 TI - Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. AB - Bisphosphonates are generally considered to act on bone resorption by binding to bone mineral and subsequently inhibiting the activity of the osteoclasts which ingest them. This has been supported by the fact that bisphosphonates adsorbed on mineralized tissue inhibit the resorbing activity of isolated osteoclasts in vitro. However, the effectiveness of different bisphosphonates determined in this system does not reflect their relative potencies in vivo. Employing the well described isolated osteoclast resorption pit assay, with ivory as the resorption substrate, we show here that this lack of correlation prevails only when the bisphosphonates are added to the mineral before addition of osteoclasts, but not when the cells are treated for a short time (5 min) before allowing them to adhere onto ivory. By using this approach with five different bisphosphonates, a stringent correlation of relative potencies was obtained with those found, both in the rat and in the human, in vivo. Furthermore, by using an osteoblastic cell line (CRP 10/30) which is a powerful promoter of osteoclastic resorption in vitro, we obtained evidence that the inhibitory effect of bisphosphonates was the result of an action on osteoblasts rather than on osteoclasts. Thus, in experiments in which the osteoblastic cells were pretreated for 5 min with bisphosphonates and then cocultured with osteoclasts, inhibition of osteoclastic resorbing activity was obtained. Moreover, it was found that this treatment resulted in a decrease of the stimulatory effect found in CRP 10/30-conditioned medium. In conclusion the present study shows that part of the osteoclast inhibiting action of the bisphosphonates is mediated through an action on osteoblasts. PMID- 8486771 TI - Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole. AB - It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10(-9) M, which decreased the diameter by 11 +/- 2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10(-11) M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10(-8) M was significantly greater with retrograde perfusion (44 +/- 6.9%, 70 +/- 5.6%, and 74 +/- 4.1%, respectively; n = 5) than with orthograde perfusion (16 +/- 4.2%, 25 +/- 2.9%, and 35 +/- 3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22 +/- 3.0%; n = 11) compared to Ef-Arts with either orthograde (9.5 +/- 2.3%; n = 8) or retrograde perfusion (1.2 +/- 2.1%; n = 6). With L-NAME pretreatment, Af Art constriction induced by 10(-10) M (14 +/- 4.0%, n = 9) and 10(-9) M Ang II (38 +/- 3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity to Ang II. PMID- 8486772 TI - Interferon-gamma inhibits macrophage apolipoprotein E production by posttranslational mechanisms. AB - Macrophage-derived apolipoprotein (apo) E and multimers of a synthetic apo E peptide display monokine-like functions by inhibiting mitogen- or antigen-driven lymphocyte proliferation. This study demonstrated how the target lymphocyte itself can modulate macrophage apo E production. The lymphokine interferon-gamma (IFN) dramatically inhibited the accumulation of apo E in the supernatant of human monocytic THP-1 cells when present during phorbol myristate acetate-induced differentiation. A similar effect was observed when IFN was added to differentiated THP-1 cells. Treatment with IFN did not change the steady-state levels of apo E mRNA. Furthermore, in the presence of IFN no increased degradation or increased uptake of extracellular apo E was detected. Pulse-chase experiments indicated that IFN reduced the accumulation of extracellular apo E and increased the degradation of intracellular apo E. The inhibitory effect of IFN on apo E production also was observed in human monocyte-derived macrophages. Thus, our data demonstrated that IFN inhibited macrophage apo E production by posttranslational mechanisms. This represents a previously uncharacterized immunoregulatory interaction and lends further support to a relationship between lipid metabolism and the immune system. PMID- 8486773 TI - High stimulatory activity of dendritic cells from diabetes-prone BioBreeding/Worcester rats exposed to macrophage-derived factors. AB - Dendritic cells (DC) present antigen and initiate T cell-mediated immune responses. To investigate the possible association of autoimmunity with DC function, we compared the accessory activity of splenic DC from Wistar/Furth (WF) and diabetes-prone (DP) BioBreeding (BB) rats. The latter develop autoimmune diabetes and thyroiditis. DC function was quantified in vitro by measuring T cell proliferation in mitogen-stimulated and mixed lymphocyte reactions. When purified without macrophage coculture, WF and DP DC displayed similar levels of accessory activity. In contrast, when purified by a method involving coculture with macrophages, DC from DP rats consistently displayed greater accessory activity. This finding could not be explained by morphological or phenotypic differences between DP and WF DC. In accessory activity assays performed after reciprocal DC cocultures with DP and WF macrophages, DP DC exhibited higher accessory activity irrespective of macrophage donor strain. We also compared the accessory activity of WF and DP DC cultured in the presence of conditioned medium and a mixture of IL-1 and GM-CSF. In all assays, DP DC exhibited higher accessory activity. In studies of (WF x DP) F1 hybrids, the high accessory activity of DP DC was observed to be heritable, and studies of WF and DP radiation chimeras indicated that the effect was an intrinsic property of the DP hematopoietic system. We conclude: (a) splenic DC from DP and WF rats possess similar basal levels of accessory potency; (b) after interaction with macrophages, DC of DP origin are capable of greater stimulatory activity than are WF DC; and (c) the mechanism responsible for this phenomenon involves differential responsiveness of DP and WF DC to macrophage-derived factors such as IL-1 and GM-CSF. PMID- 8486774 TI - Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans. AB - The expression and localization of PDGF beta receptors and PDGF-AB/BB in human healing wounds was evaluated by immunohistochemical techniques and in situ hybridization. Expression of PDGF beta receptor protein and PDGF-AB/BB were analyzed in wound margin biopsies using the PDGFR-B2 and PDGF 007 antibodies. PDGF beta receptor expression was minor in normal skin. An increased expression of PDGF beta receptor protein was prominent in vessels in the proliferating tissue zone in wounds as early as 1 d after surgery and was apparent < or = 4 wk after surgery. There was also a concordant increase in PDGF beta receptor mRNA detected by in situ hybridization. PDGF-AB/BB was present in healing wounds as well as in normal skin. In normal skin, expression of PDGF-AB/BB was confined to peripheral nerve fibers and to solitary cells of the epidermis and of the superficial dermis. In wounds, infiltrating mononuclear cells also stained for PDGF-AB/BB. To identify cell types expressing PDGF AB/BB and PDGF beta receptors, respectively, we performed double immunofluorescence stainings. PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages. PDGF-AB/BB colocalized with neurofilaments, it was present in Langerhans cells of the epidermis and in HLA-DR positive cells located in the epidermal/dermal junction area. Of the macrophages infiltrating the wound, 43 +/- 18% stained positively for PDGF AB/BB. Since PDGF-AB/BB and PDGF beta receptors are expressed in the healing wound, two essential prerequisites for a role of PDGF in wound healing are fulfilled. PMID- 8486775 TI - Demonstration of GAD-65 as the main immunogenic isoform of glutamate decarboxylase in type 1 diabetes and determination of autoantibodies using a radioligand produced by eukaryotic expression. AB - Plasmids containing cDNA for the rat 67- and 65-kD isoforms of glutamate decarboxylase (GAD-67 and GAD-65) were expressed in COS-cells, and lysates of [35S]methionine-labeled cells were used for immunoprecipitations. Sera from 38 patients with type 1 (insulin-dependent) diabetes mellitus, which precipitated a 64-kD antigen from rat islets, reacted with recombinant GAD-65 in relation to their anti-64-kD titers. The eight strongest sera also precipitated recombinant GAD-67, suggesting that certain epitopes are common to both isoforms. Subsequently, [35S]methionine-labeled GAD-65 was purified from COS cell lysates and employed in a binding assay with 50 sera of patients with recent onset of type 1 diabetes mellitus. 38 sera (76%) precipitated labeled GAD-65 with titers that correlated with islet cell antibodies (ICA), determined in a standard immunofluorescence assay. 2 sera were GAD positive but ICA negative, 4 were positive only for ICA, and 6 were negative for both GAD and ICA, as were the sera of 20 controls. The data illustrate that antibodies against GAD-65 are present in a majority of patients with type 1 diabetes mellitus and that autoantibodies against other islet cell antigens also exist. The radioligand-binding assay, which is convenient and sensitive for detecting GAD antibodies, will facilitate the screening of individuals with autoimmune islet cell disease. PMID- 8486776 TI - Low expression allele alpha LELY of red cell spectrin is associated with mutations in exon 40 (alpha V/41 polymorphism) and intron 45 and with partial skipping of exon 46. AB - The alpha V/41 polymorphism of erythroid alpha-spectrin has been characterized initially by an increased susceptibility to proteolysis of the alpha IV-alpha V domain junction (Alloisio N., L. Morle, J. Marechal, A.-F. Roux, M.-T. Ducluzeau, D. Guetarni, B. Pothier, F. Baklouti, A. Ghanem, R. Kastally, et al. 1991. J. Clin. Invest. 87:2169-2177). Until now, it has been found associated invariably with a low expression level of the corresponding alpha chain. Among 61 chromosomes investigated in French and North African individuals or kindreds, we observed 19 chromosomes with the alpha V/41 polymorphism. With no single exception, the latter displayed a point mutation in exon 40 (Leu-->Val; CTA- >GTA) at position alpha 1857. According to the triple helical model of spectrin structure, this change accounts for the peptide maps' abnormalities. Sequencing the entire alpha V domain cDNA disclosed, in addition, a partial skipping of exon 46. At the gene level, a substitution (C-->T) was evidenced at nucleotide -12 of intron 45. This mutation appeared linked to the exon 40 mutation in 17 chromosomes, again with no single exception, among 53 examined chromosomes. We hypothesized that the lack of exon 46 would hamper the nucleation process and eventually account for the low expression feature. The present doubly mutated allele was renamed allele alpha LELY (low expression, Lyon). PMID- 8486777 TI - Identification of the human NHE-1 form of Na(+)-H+ exchanger in rabbit renal brush border membranes. AB - To study the relation between the human Na(+)-H+ exchanger (NHE-1) and the renal brush border membrane (BBM) Na(+)-H+ exchanger, polyclonal antibodies to synthetic peptides representing a putative external (Ab-E) and an internal cytosolic domain (Ab-I) of human NHE-1 were generated in rabbits. Western immunoblot analyses indicated that both antibodies recognized a 97-kD protein in rabbit renal BBM but not basolateral membranes (BLM). Octyl glucoside-extracted rabbit renal BBM proteins also contained the 97-kD polypeptide as did a fraction eluted from an anion-exchange column with 0.2 M NaCl (fraction A). A fraction eluting between 0.2 and 0.4 M NaCl (fraction B) did not contain this protein. Prior reconstitution studies have indicated that Na(+)-H+ exchange activity is higher significantly in fraction B than fraction A. Administration of NH4Cl for 3 7 d to rabbits, a stimulus known to increase renal BBM Na(+)-H+ exchange activity, did not result in a change in expression of the 97-kD protein in either renal BBM or BLM. The results indicate that affinity-purified polyclonal antibodies to two separate domains of the human Na(+)-H+ exchanger recognize a 97 kD protein in rabbit renal BBM but not BLM. The dissociation between recognition of the 97-kD protein using antibodies and the majority of functional Na(+)-H+ exchange activity after chromatographic fractionation of solubilized BBM proteins and in native BBM after administration of NH4Cl suggest that rabbit renal BBM contains more than one form of Na(+)-H+ exchanger. PMID- 8486778 TI - P53 mutation in acute T cell lymphoblastic leukemia is of somatic origin and is stable during establishment of T cell acute lymphoblastic leukemia cell lines. AB - Samples donated by patients with T cell acute lymphoblastic leukemia (T-ALL) were screened for mutations of the p53 tumor suppressor gene. Peripheral blood cells of T-ALL relapse patient H.A. were found to possess a heterozygous point mutation at codon 175 of the p53 gene. To determine whether this was an inherited mutation, a B cell line (HABL) was established. Leukemic T cell lines (HATL) were concurrently established by growing peripheral blood leukemic T cells at low oxygen tension in medium supplemented with IGF-I. Previously we had shown that > 60% of leukemic T cell lines possessed mutations in the p53 gene (Cheng, J., and M. Hass. 1990. Mol. Cell. Biol. 10:5502), mutations that might have originated with the donor's leukemic cells, or might have been induced during establishment of the cell lines. To answer whether establishment of the HATL lines was associated with the induction of p53 mutations, cDNAs of the HATL and HABL lines were sequenced. The HATL lines retained the same heterozygous p53 mutation that was present in the patient's leukemic cells. The HABL line lacked p53 mutations. Immunoprecipitation with specific anti-p53 antibodies showed that HATL cells produced p53 proteins of mutant and wild type immunophenotype, while the HABL line synthesized only wild-type p53 protein. The HATL cells had an abnormal karyotype, while the HABL cells possessed a normal diploid karyotype. These experiments suggest that (a) p53 mutation occurred in the leukemic cells of relapse T-ALL patient HA; (b) the mutation was of somatic rather than hereditary origin; (c) the mutation was leukemia associated; and (d) establishment of human leukemia cell lines needs not be associated with in vitro induction of p53 mutations. It may be significant that patient HA belonged to a category of relapse T-ALL patients in whom a second remission could not be induced. PMID- 8486779 TI - Effects of low dose oral contraceptives on very low density and low density lipoprotein metabolism. AB - Oral contraceptives (OC) raise plasma triglyceride and VLDL levels, which may be of concern, since some conditions characterized by elevated triglycerides are associated with atherosclerosis. To identify the responsible mechanism, we studied 11 healthy premenopausal women, 5 of whom were taking OC containing 0.035 mg ethinyl estradiol, and 6 of whom were not. Their rates of VLDL and LDL metabolism were measured by endogenously labeling apoB, the protein component of VLDL and LDL, by an intravenous infusion of deuterated leucine. OC use had the greatest effect on the large, triglyceride-rich VLDL subfraction (Sf 60-400), increasing plasma levels threefold and production rates fivefold (P < 0.05). Among OC users, small VLDL (Sf 20-60) levels were 2.2 times higher, and production rates were 3.4-fold higher (P < 0.05). The fractional catabolic rates of large and small VLDL were similar among OC users and nonusers. LDL levels and metabolic rates were not significantly different between the two groups. Thus, contemporary low dose OC substantially raise VLDL levels by increasing the production rate of large, triglyceride-rich VLDL, and not by slowing VLDL catabolism. Since VLDL catabolism is not impaired, we speculate that the hypertriglyceridemia induced by OC may be less atherogenic than that of hypertriglyceridemia resulting from impaired lipolysis. This may explain why long term OC use does not appear to promote atherosclerosis. PMID- 8486780 TI - Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment. AB - The platelet GP Ib-IX receptor supports platelet adhesion and activation by binding to vWf in the exposed subendothelial matrix. An abnormal GP Ib-IX complex exists in platelet-type or pseudo-von Willebrand disease and has a characteristic increased affinity for soluble vWf resulting in impaired hemostatic function due to the removal of larger vWf multimers from the circulation. Genetic studies within an afflicted family have demonstrated that the disease is linked to a Gly233-->Val amino acid substitution within the alpha-subunit of the oligomeric GP Ib-IX complex (Miller, J.L., D. Cunningham, V.A. Lyle, and C. L. Finch. 1991. Proc. Natl. Acad. Sci. USA. 88:4761-4765). To evaluate the functional consequences of this mutation, we constructed a recombinant analogue of the alpha subunit of GP Ib containing Val233. Experiments comparing molecules with either Gly233 or Val233 revealed that the Val substitution generates a molecule with increased affinity for vWf. The recombinant fragment reproduces the functional abnormality of the GP Ib-IX complex in platelet-type von Willebrand disease, thus establishing the molecular basis of the bleeding disorder within this family. Moreover, it becomes apparent that structural elements responsible for the regulation of hemostasis through modulation of vWf affinity for platelets reside within the alpha-subunit of the GP Ib-IX complex. PMID- 8486781 TI - Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles. AB - Recent evidence suggests that the potent constrictor peptide, endothelin (ET) has a mediating role in cyclosporine A (CsA)-related renal vasoconstriction. However, the nature of the CsA-ET interaction and effect on the renal vasculature is uncertain. The purpose of the present study was twofold: (a) to determine if CsA exposure caused direct local release of ET from the endothelium of the renal microvasculature and (b) to determine if locally generated ET has paracrine effects on the underlying vascular smooth muscle to induce vasoconstriction. Experiments were performed in isolated rat renal arterioles. First it was determined that both afferent arteriole (AA) and efferent arteriole (EA) exhibited concentration-dependent decreases in lumen diameter to increasing molar concentrations of CsA. The AA was more sensitive to the vasoconstrictive effects of CsA than the EA. Next, the blocking effect of a recently synthesized putative ETA receptor antagonist was verified in both the AA and EA, where it was found that the cyclic peptide cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp totally inhibited the vasoconstriction observed with ET addition. Finally, the role of locally stimulated ET in CsA-induced vasoconstriction was tested by determining the effect of the ETA receptor antagonist on CsA-induced AA and EA constriction. In the AA the vasoconstrictor effect of 10(-11) M CsA was completely blocked by the ETA receptor antagonist. However, in contrast to AA, 10(-11) M CsA in EA in the presence of the ETA receptor antagonist decreased EA lumen diameter by a mean of 41% from baseline (4.80 +/- 0.75 microns vs 7.80 +/- 0.84 microns, P < 0.05). This change in lumen diameter was similar to that induced by CsA alone. These data suggest that CsA directly constricts renal microvessels. This effect is mediated by ET in the AA but not the EA. PMID- 8486782 TI - von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure. AB - Variant von Willebrand disease designated as type I New York or type Malmo is characterized by enhanced ristocetin-induced platelet agglutination with normal von Willebrand factor multimeric distribution in plasma. We have studied four such patients belonging to three unrelated families and found in all of them a unique cytosine-to-thymine transition changing the codon for Pro503 (CCG) to Leu (CTG). In three patients the mutant allele also had a silent mutation in the codon for Ser500 (TCG-->TCA). Both nucleotide changes are present in the von Willebrand factor pseudogene; however, the characterization of distinctive markers where the gene and pseudogene differ, as well as the examination of amplified cDNA derived from platelet mRNA, confirmed that the abnormality occurs in the von Willebrand factor gene of the patients. Moreover, recombinant expression of the isolated glycoprotein Ib-binding domain of von Willebrand factor provided direct evidence that the Pro503-->Leu mutation is responsible for enhanced platelet reactivity to lower ristocetin concentrations. These results define a new structural element affecting the affinity of von Willebrand factor for glycoprotein Ib and establish the molecular basis of a variant form of von Willebrand disease. PMID- 8486783 TI - Renal acid excretion and intracellular pH in salt-sensitive genetic hypertension. AB - Acid-base status and renal acid excretion were studied in the Dahl/Rapp salt sensitive (S) rat and its genetically salt-resistant counterpart (R). S rats developed hypertension while on a very high salt diet (8%) and while on a more physiological salt diet (1%) and remained normotensive while on a very low salt diet (0.08%). Under the high salt diet, intracellular pH measured in freshly isolated thymic lymphocytes using 2',7'-bis (carboxyethyl)-5 (6) carboxyfluorescein acetomethyl ester, a pH-sensitive dye, was lower in S than in R rats both when measured in the presence of HCO3/CO2 (7.32 +/- 0.02 vs. 7.38 +/- 0.02, respectively, P < 0.05) and in its absence (7.18 +/- 0.04 vs. 7.27 +/- 0.02, respectively, P < 0.05). Under the high salt diet, net acid excretion was higher in S than R rats (1,777 +/- 111 vs. 1,017 +/- 73 muEq/24 h per 100 g body wt, respectively, P < 0.001), and this difference was due to higher rates of both titratable acid and ammonium excretion. Directionally similar differences in intracellular pH and net acid excretion between S and R rats were also observed in salt-restricted animals. In S and R rats placed on a normal salt intake (1%) and strictly pair-fed to control food intake as a determinant of dietary acid, net acid excretion was also higher in S than in R rats (562 +/- 27 vs. 329 +/- 21 muEq/24 h per 100 g, respectively, P < 0.01). No significant difference in either blood pH or bicarbonate levels were found between S and R rats on either the 0.08%, 1%, or 8% salt diets. We conclude that renal acid excretion is augmented in the salt-sensitive Dahl/Rapp rat. Enhanced renal acid excretion may be a marker of increased acid production by cells from subjects with salt-sensitive hypertension. PMID- 8486784 TI - Tissue infiltration in a CD8 lymphocytosis syndrome associated with human immunodeficiency virus-1 infection has the phenotypic appearance of an antigenically driven response. AB - HIV-1 infection may initiate to an HLA-associated response designated diffuse infiltrative lymphocytosis syndrome, characterized by increased numbers of circulating CD8 T cells that infiltrate salivary glands, lungs, gastrointestinal tract, and kidneys. Since this response could either be an antigenically driven process induced by HIV-1 or a lymphoproliferation of cells with neoplastic or unusual features, we sought to define the phenotype of the cellular populations, the nature of tissue derangement, and the tissue localization of virus in diffuse infiltrative lymphocytosis syndrome. Circulating CD8 T cells were greatly increased while CD4 T cell numbers remained in the range found in asymptomatic seropositive persons. The majority of CD8 and CD4 T cells in both blood and tissues had the memory phenotype of CD29+ (beta 1 integrin) and CD11a+/CD18 (beta 2 integrin) expression, but lacked markers of recent activation. A proportion of the circulating CD8 T cells also expressed CD57 (Leu 7) but not other markers of natural killer cells. HIV-encoded proteins were identified in tissue macrophages located in periacinar areas of the salivary glands. CD54 (intercellular adhesion molecule-1), a ligand for the CD11a integrin, was strongly expressed on postcapillary venule endothelium within lymphoid foci, and HLA-DR molecules were found on limited regions of ductular epithelium adjacent to lymphoid aggregates. These findings suggest that (a) the visceral lymphocytic infiltration in diffuse infiltrative lymphocytosis syndrome is an antigen-driven, and MHC-determined, host immune response to an element associated with HIV-1 infection, and (b) that the specific adhesive molecule interactions mediating the cellular influx, as well as the subsequent tissue damage, reflect altered patterns of gene expression in tissues undergoing an immune response. PMID- 8486785 TI - Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. AB - Angiotensin (Ang) II stimulates hypertrophic growth of vascular smooth muscle cells (VSMC). Accompanying this growth is the induction of the expression of growth-related protooncogenes (c-fos, c-jun, and c-myc), as well as the synthesis of the autocrine growth factors, such as PDGF-A and TGF-beta 1. In this study, we demonstrate further that Ang II also induces the synthesis of basic fibroblast growth factor (bFGF), a potent mitogen for VSMC. To examine how these factors interact to modulate the growth response of VSMC to Ang II, we used antisense oligomers to determine the relative contribution of these three factors. Treatment of confluent, quiescent smooth muscle cells with specific antisense oligomers complementary to bFGF, PDGF-A, and TGF-beta 1 efficiently inhibited the syntheses of these factors. Our results demonstrate that in these VSMC, TGF-beta 1 affects a key antiproliferative action, modulating the mitogenic properties of bFGF. Autocrine PDGF exerts only a minimal effect on DNA synthesis. An imbalance in these signals activated by Ang II may result in abnormal VSMC growth leading to the development of vascular disease. PMID- 8486786 TI - Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect. AB - Approximately 2% of Caucasians and African-Americans are homozygous for a nonsense mutation in exon 2 of the AMPD1 (AMP deaminase) gene. These individuals have a high grade deficiency of AMPD activity in their skeletal muscle. More than 100 patients with AMPD1 deficiency have been reported to have symptoms of a metabolic myopathy, but it is apparent many individuals with this inherited defect are asymptomatic given the prevalence of this mutant. Results of the present study provide a potential molecular explanation for "correction" of this genetic defect. Alternative splicing eliminates exon 2 in 0.6-2% of AMPD1 mRNA transcripts in adult skeletal muscle. Expression studies document that AMPD1 mRNA, which has exon 2 deleted, encodes a functional AMPD peptide. A much higher percentage of alternatively spliced transcripts are found during differentiation of human myocytes in vitro. Transfection studies with human minigene constructs demonstrate that alternative splicing of the primary transcript of human AMPD1 is controlled by tissue-specific and stage-specific signals. Alternative splicing of exon 2 in individuals who have inherited this defect provides a mechanism for phenotypic rescue and variations in splicing patterns may contribute to the variability in clinical symptoms. PMID- 8486787 TI - Recombinant human insulin-like growth factor-I accelerates recovery and reduces catabolism in rats with ischemic acute renal failure. AB - This study evaluated whether recombinant human insulin-like growth factor-I (rhIGF-I) enhances recovery of renal function and reduces catabolism in rats with ischemic acute renal failure (ARF). ARF and sham rats received subcutaneous injections of either rhIGF-I or vehicle three times daily starting 5 h after surgery. Serum creatinine and urea, which initially rose similarly in the ARF+vehicle and ARF+rhIGF-I rats, increased more slowly after commencing the rhIGF-I injections. 72 h after surgery, the ARF+rhIGF-I rats, in comparison with ARF+vehicle animals, showed significantly greater renal plasma flow and filtration fraction, a fivefold higher glomerular filtration rate, greater renal cortical IGF-I levels, increased proliferating cell nuclear antigen expression in proximal tubule nuclei and enhanced DNA synthesis in the renal cortex, corticomedullary junction, glomeruli, and tubules as demonstrated by [3H]thymidine incorporation and in corticomedullary junction tubules as determined by autoradiography. Estimated total nitrogen output (ETNO) was greater in ARF+vehicle than in ARF+rhIGF-I or sham rats throughout the study. ETNO in ARF+rhIGF-I rats returned to sham values by the second day after surgery. 72 h after surgery, protein degradation was increased and protein synthesis reduced in the epitrochlearis muscle of ARF+vehicle as compared with ARF+rhIGF-I or sham+vehicle rats. Thus, treatment with rhIGF-I starting 5 h after inducing ischemic ARF in rats increases recovery of renal function, enhances formation of new renal tubular cells, lowers protein degradation, and increases protein synthesis in skeletal muscle and reduces net catabolism. PMID- 8486788 TI - Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. AB - Differentiation therapy may provide an alternative for treatment of cancers that do not respond to cytotoxic chemotherapy or hormonal manipulations. This hypothesis led us to evaluate the effect of a nontoxic differentiation inducer, sodium phenylacetate (NaPA), on hormone-refractory prostate cancer, the second most common cause of cancer deaths in men. NaPA treatment of androgen-independent PC3 and DU145 prostate cell lines, like that of hormone-responsive LNCaP cultures, resulted in dose-dependent inhibition of cell proliferation. Similar treatments were not significantly inhibitory to replicating normal endothelial cells and skin fibroblasts. In addition to the selective cytostatic effect, NaPA induced reversion of the prostatic cells to a nonmalignant phenotype, evidenced by their reduced invasiveness and loss of tumorigenicity in athymic mice. Phenotypic reversion was accompanied by alterations in gene expression, including selective reduction in tumor growth factor-beta 2 mRNA levels and increased amounts of class I major histocompatibility complex HLA transcripts. Furthermore, there was a decrease in tumor-associated proteolysis mediated by urokinase plasminogen activator, a molecular marker of disease progression in humans. When tumor cells were treated with NaPA together with suramin, a drug with demonstrable activity in patients, there was complete abrogation of cell growth under conditions in which each treatment alone produced only a partial effect. The in vitro antineoplastic activity was observed with drug concentrations that have been achieved in humans with no significant toxicities, suggesting that PA, used alone or in combination with other antitumor agents, warrants evaluation in the treatment of advanced prostatic cancer. PMID- 8486789 TI - Differential expression of mutant and normal beta T3 receptor alleles in kindreds with generalized resistance to thyroid hormone. AB - Thyroid hormone resistance (THR) is primarily an autosomal dominant inherited disease characterized by resistance of pituitary and peripheral tissues to the action of thyroid hormone. We investigated whether the heterogeneous phenotypic features that occur not only among kindreds but also within the same kindred might be due to the expression of differing ratios of mutant and normal receptors in tissues. Using an allele-specific primer extension method, we determined the relative expression of normal and mutant mRNAs from the fibroblasts of affected and unaffected members of two kindreds with TRH: A-H and N-N. While two affected members of A-H, as expected, had nearly equal amounts of normal and mutant hTR beta mRNA, two other members had mutant mRNA levels that accounted for at least 70% of the hTR beta mRNA. Phenotypic variability within and between kindreds with generalized resistance to thyroid hormone GRTH may be due to this differential expression of the mutant and wild type mRNA. Furthermore, when several clinical parameters of THR were compared in several affected members from two kindreds with GRTH, we found that two cases in one kindred exhibited a high mutant-to normal hTR beta ratio and had considerably more bone resistance during their development. In certain kindreds with THR, differing ratios of normal and mutant hTR receptors may be age and growth related and may account for the reported attenuation of phenotypic symptoms with age. PMID- 8486790 TI - Defective major histocompatibility complex class I expression on lymphoid cells in autoimmunity. AB - Lymphocytes from patients with insulin-dependent diabetes mellitus (IDDM), a chronic autoimmune disease, have recently been shown to have decreased surface expression of MHC class I antigens. Since IDDM and other autoimmune diseases share a strong genetic association with MHC class II genes, which may in turn be linked to genes that affect MHC class I expression, we studied other autoimmune diseases to determine whether MHC class I expression is abnormal. Fresh PBLs were isolated from patients with IDDM, Hashimoto's thyroiditis, Graves' disease, systemic lupus erythematosis, rheumatoid arthritis, and Sjogren's syndrome. Nondiabetic and non-insulin-dependent diabetes mellitus patients served as controls. MHC class I expression was measured with a conformationally dependent monoclonal antibody, W6/32. Freshly prepared PBLs from the autoimmune diseases studied and the corresponding fresh EBV-transformed B cell lines had decreased MHC class I expression compared with PBLs from normal volunteers and non-insulin dependent (nonautoimmune) diabetic patients. Only 3 of more than 180 donors without IDDM or other clinically recognized autoimmune disease had persistently decreased MHC class I expression; one patient was treated with immunosuppressive drugs, and subsequent screening of the other two patients revealed high titers of autoantibodies, revealing clinically occult autoimmunity. Patients with nonautoimmune inflammation (osteomyelitis or tuberculosis) had normal MHC class I expression. Autoimmune diseases are characterized by decreased expression of MHC class I on lymphocytes. MHC class I expression may be necessary for self tolerance, and abnormalities in such expression may lead to autoimmunity. PMID- 8486791 TI - Protamine and protamine-insulins exacerbate the vascular response to injury. AB - Endothelial cells and smooth muscle cells produce heparinlike compounds that are growth inhibitory for vascular smooth muscle cells, and it has been suggested that these compounds play a regulatory role that is perturbed with vascular injury. Indeed, exogenous heparin preparations effectively suppress smooth muscle cell proliferation following injury imposed on vascular endothelium. We now report that protamine, an agent that binds heparin and negates its anticoagulant properties, has potent stimulatory effects on vascular smooth muscle cell proliferation. The administration of protamine, alone or as part of commonly used insulin preparations, stimulated the proliferation of cultured smooth muscle cells, exacerbated vascular smooth muscle cell proliferative lesions in laboratory rats, and interfered with the growth-inhibitory effects of heparin in culture and in vivo. These results confirm the importance of endogenous heparinlike compounds in arterial homeostasis and may require reconsideration of protamine use following vascular reparative procedures and in diabetics. PMID- 8486792 TI - Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. AB - The mechanism by which soluble mediators of immune cell origin depress myocardial contractility, either globally as in systemic sepsis, or regionally in areas of inflammatory myocardial infiltrates, remains unclear. When freshly isolated ventricular myocytes from adult rat hearts were preincubated for at least 24 h in medium conditioned by endotoxin (LPS)-activated rat alveolar macrophages, their subsequent inotropic response to the beta-adrenergic agonist isoproterenol was reduced from 225 +/- 19% to 155 +/- 10% of the baseline amplitude of shortening (mean +/- SEM, P < 0.05). Neither baseline contractile function nor the contractile response to high extracellular calcium were affected. To determine whether an endogenous nitric-oxide (NO)-signaling pathway within ventricular myocytes was responsible for their decreased responsiveness to isoproterenol, the L-arginine analogue L-NMMA was added to the preincubation medium. While L-NMMA did not affect baseline contractile function or the response of control myocytes to isoproterenol, it completely restored the positive inotropic response to isoproterenol in myocytes preincubated in LPS-activated macrophage medium. Release of NO by ventricular myocytes following exposure to activated macrophage medium was detected as an increase in cGMP content in a reporter-cell (RFL-6) bioassay and also as increased nitrite content in myocyte-conditioned medium. Thus, the depressed contractile response of adult rat ventricular myocytes to beta-adrenergic agonists by a 24-h exposure to soluble inflammatory mediators is mediated at least in party by induction of an autocrine NO signaling pathway. PMID- 8486794 TI - Victims of traffic accidents: incidence and prevention of post-traumatic stress disorder. AB - The psychological consequences of traffic accidents have been rarely the subject of research. Responses of serious traffic accidents and the effects of an outreach program for victims were studied in a research project. Subjects selected from police registers participated in a preventive counseling program or in a monitoring group. Foci of this study were the way in which the subjects coped with the event and the symptoms that might develop. Measurements were carried out 1 month and 6 months after the accident. The results indicate that an average of about 10% of the victims suffer from post-traumatic stress disorders and that although counseling is appreciated by victims, it could not be proven that it was effective in preventing disorders. PMID- 8486793 TI - 5'-adenosine monophosphate is the neutrophil-derived paracrine factor that elicits chloride secretion from T84 intestinal epithelial cell monolayers. AB - Neutrophil transmigration across intestinal epithelia is thought to contribute to epithelial dysfunction and characterizes many inflammatory intestinal diseases. Neutrophils activated by factors, normally present in the lumen, release a neutrophil-derived secretagogue activity to which intestinal epithelia respond with an electrogenic chloride secretion, the transport event which underlies secretory diarrhea. Using sequential ultrafiltration, column chromatographic, and mass and Raman spectroscopic techniques, neutrophil-derived secretagogue was identified as 5'-AMP. Additional studies suggested that neutrophil-derived 5'-AMP is subsequently converted to adenosine at the epithelial cell surface by ecto-5' nucleotidase and that adenosine subsequently activates intestinal secretion through adenosine receptors on the apical membrane of target intestinal epithelial cells. These findings suggest that this ATP metabolite may serve as a neutrophil-derived paracrine mediator that contributes to secretory diarrhea in states of intestinal inflammation. PMID- 8486795 TI - The measurement and mismeasurement of ophidiophobia in analogue research: a procedural review. AB - The adequacy of current paper-and-pencil measures of ophidiophobia (fear of snakes) was analyzed by reviewing the subject selection procedures in 24 published articles with the restriction that the procedures involve some form of self-report. The sample characteristics and selection procedures of these studies were reviewed in detail. We conclude that the recommendations and conclusions of these studies should not be accepted due to limited generalizability. Paper-and pencil measures are excellent initial selection devices, but cannot stand alone in selecting ophidiophobics from the general population. PMID- 8486796 TI - Factors associated with the psychological well-being of adults with acute leukemia in remission. AB - The relationships among coping responses, social support, personality factors, and psychological well-being in adults with acute leukemia in remission were studied. The psychological well-being measure was related to quality of life. Forty persons (21 male, 19 female), average age 47 years and average time since diagnosis of 24 months, completed demographic questions, the PRF-E, the Symptom Distress Scale, a Coping Responses inventory, the modified Social Support Questionnaire, and the General Behavior Inventory. An R of .80 was obtained between psychological well-being and Endurance, Affiliation, Cognitive Structure, Autonomy, and Nurturance. Findings were related to fighting spirit and confronting coping style, concepts associated with psychological well-being and longevity in cancer patients. PMID- 8486798 TI - Cognitive distortions and irrational beliefs in post-traumatic stress, anxiety, and depressive disorders. AB - This study examined the validity of PTSD by comparing the dysfunctional cognitions found in a PTSD group, a clinical group (anxiety or depression), and a nonclinical group. Subjects completed the Millon Clinical Multiaxial Inventory II, the Impact of Event Scale, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Cognitive Error Questionnaire, and the Survey of Personal Beliefs. Results revealed that PTSD and clinical groups were significantly more depressed and anxious than nonclinical subjects. Unlike the PTSD group, only the clinical group endorsed more dysfunctional cognitions than the nonclinical group, which supports the uniqueness of the PTSD group as differing cognitively from clinical groups. PMID- 8486797 TI - Sexually and physically abused adolescents: an empirical search for PTSD. AB - Recently, clinical manifestations of post-traumatic stress disorder (PTSD) in children and adolescents have been investigated, yet little is known about its assessment or diagnosis. Few empirically based studies appear in the PTSD literature on non-adult populations. Data were collected from 19 physically and sexually abused adolescents (aged 13-18 years) who were living in a group home setting. Subjects were administered the MMPI, Beck Depression Inventory (BDI), and Spielberger State Trait Anxiety Inventory (STAI). Results suggest that the subjects were moderately depressed and anxious, but that these adolescents did not manifest significant symptomatology of PTSD similar to that seen in adult, civilian PTSD populations using comparable MMPI measures. Implications of these findings for assessment purposes are discussed. PMID- 8486799 TI - Male perceptions of female attractiveness: the effects of targets' personal attributes and subjects' degree of masculinity. AB - This study examined the relationship between the degree of sexist beliefs held toward women by male subjects and their perceptions of attractiveness of females described as possessing either masculine or feminine personality characteristics. One hundred twenty-two undergraduate males were given the Macho Scale, the Auburn University Personal Behavior Summary, a biodata sheet, and were asked to judge previously rated photographs of women along a dimension of attractiveness. Results demonstrated that males perceived physically unattractive and average females described as affectionate and compassionate as more attractive than similarly rated females described as independent and assertive. High Macho subjects viewed females as less attractive than low Macho subjects. Physical attractiveness of the male subjects was largely unrelated to their ratings of the females. PMID- 8486800 TI - A self-rating scale for the assessment of posttraumatic stress disorder in Dutch Resistance veterans of World War II. AB - The present study reports on the development of a Dutch PTSD scale based on the DSM-III criteria for PTSD. Test-retest reliability was .91. The scale showed an internal consistency with a coefficient alpha of .88. Factor analysis on a large sample of Resistance veterans (N = 967) yielded six factors, which represent intrusive thoughts, physiological reactions, detachment, rage, active confrontation, and guilt. PMID- 8486801 TI - The differential responding of college students to subtle and obvious MCMI subscales. AB - This study investigated the differential responding of 49 male and 92 female college students to subtle and obvious MCMI scale items. It had been predicted that item subtlety would be correlated positively with item endorsement. This prediction was supported across all 175 MCMI items (r = .34). In addition, subjects endorsed a greater percentage of subtle than obvious subscale items for eight Basic Personality scales and two of three Pathological Personality scales. However, this pattern was not consistent for the nine Symptom Disorder scales. It also had been predicted that gender would moderate subjects' differential responding to subtle and obvious items, whereby males would show a greater tendency than females to endorse relatively more subtle than obvious items. This prediction was not supported. PMID- 8486802 TI - Reading level of the Dissociative Experiences Scale. AB - Reading difficulty values based upon the Flesch reading grade level and reading ease score (Flesch, 1949) were calculated for the 28 items of the Dissociative Experiences Scale (DES; Bernstein & Putnam, 1986). Item reading levels ranged from the sixth to more than the thirteenth grade. According to the reading level formula, 43% of the items required at least a high school education. The reading ease estimate suggested that only 1 item required at least 12 years of schooling. Overall, a tenth- to eleventh-grade reading level was required for the entire DES. For persons with confirmed or suspected reading difficulties, interpretation of the DES should be made cautiously. PMID- 8486803 TI - Unidimensionality of SCL-90-R scales in adult and adolescent crisis samples. AB - The factorial structure and consistency of the SCL-90-R dimensions were investigated in adult (90 male, 94 female) and adolescent (93 male, 120 female) admissions to a crisis intervention unit by means of principal components analysis. All four samples of subjects demonstrated one large factor, which accounted for 66 to 70% of the variance. Second factors in each sample contributed insignificant variance. Factorial invariance across male, female, and adult, adolescent samples was observed. Results suggest the SCL-90-R to be a unidimensional measure in a crisis context. Appropriateness of profile scores within such a context is discussed. PMID- 8486804 TI - Psychometric evaluation of post-traumatic stress disorder: the Multidimensional Personality Questionnaire as an adjunct to the MMPI. AB - Two groups of Vietnam veterans--Post-traumatic stress disorder (PTSD, n = 17) and non-PTSD (n = 80)--were developed from a sample of treatment-seeking alcohol abusers. The subjects completed a Combat Experiences Questionnaire, a PTSD Symptom Scale, the MMPI, and the Multidimensional Personality Questionnaire (MPQ). The MPQ proved to be a useful adjunct to the MMPI in describing the major manifestations of PTSD among alcohol-abusing veterans. PMID- 8486805 TI - Predicting Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ scores from the Luria-Nebraska Neuropsychological Battery (Form I). AB - The study examined a modification of two sets of previously published LNNB derived WAIS IQ estimates in order to estimate WAIS-R IQs in a sample of neuropsychiatric patients. Findings suggested that the modification will allow practicing clinicians to estimate WAIS-R IQs with a level of accuracy similar to that found in previous research. The level of predictive accuracy for WAIS-R FSIQ and VIQ was somewhat higher than would be expected on the basis of previous research, which suggests that the modified McKay, Golden, Moses, Fishburne, and Wisniewski (1981) formulae for estimating IQ may be more accurate than previously thought. The correlation matrix of WAIS-R subtests and LNNB Form I clinical and summary scales also is described. PMID- 8486806 TI - Factor structure of emotional and cognitive behaviors for normals and neurologically impaired patients. AB - This study examined the factor structure of 68 affective, cognitive, and behavioral symptoms often reported with neurological impairment. The responses of 199 subjects to a behavioral inventory were submitted to an exploratory factor analysis. The results demonstrated that the instrument could be reduced to 16 homogeneous factors, which were able to explain 67% of the instrument's total variability. These factors were entered into a discriminant analysis that examined neurologically impaired patients and normal controls. Eleven of the 16 factors formed a linear composite that discriminated between these two groups with approximately 94% accuracy. PMID- 8486807 TI - Left temporal lobe brain damage pattern on the WAIS, addendum. AB - This study added Digit Span to an index investigated in a previous study. An index score, in which the WAIS Vocabulary and Information were more impaired than Similarities and Digit Span, indicated left temporal lobe damage. Using subjects with damage restricted to a single lobe of the brain, the index was found to be significantly more related to the left temporal lobe than to any other part of the brain. PMID- 8486808 TI - Wechsler Memory Scale-Revised in closed head injury. AB - This study was undertaken to determine the ability of the Wechsler Memory Scale Revised (WMS-R) to differentiate a group of closed head injury patients from a group of controls and determine how injury severity and attentional deficits are associated with WMS-R performance. The relationship of WMS-R performance to everyday memory also was assessed. The head injured group performed more poorly than controls on all five WMS-R indices and exhibited greater impairments on tasks that measure retention. In the original sample only the Visual Memory Index correlated with injury severity; in a larger sample, all four memory indices correlated modestly with injury severity. Patients who performed more poorly on the WMS-R also received poorer ratings on an independent assessment of everyday memory. PMID- 8486809 TI - Factor structure of the WISC-R in children with traumatic brain injury. AB - The factor structure of the WISC-R was examined in a sample of 108 children with traumatic brain injury. Principal factor analysis of 11 WISC-R subtests yielded three factors, which were subjected to varimax rotation. The rotated factor pattern suggested the existence of a Verbal Comprehension factor, a Perceptual Organization factor, and a somewhat weaker third factor. The meaning and implications of this third factor are discussed. PMID- 8486810 TI - Previewing: a developmental principle that promotes the therapeutic use of metaphor. AB - When one is treating mother-infant dyads psychotherapeutically, the infant's inchoate language skills render the traditional use of metaphor ineffective. This paper discusses how a developmental principle, labeled previewing, may function like a metaphor and be used to address the therapeutic needs of the dyad. Previewing and metaphor also may complement each other in the treatment of adults in individual therapy. Previewing--like metaphors--may provide a means of addressing interpersonal issues, may function as a shared language that promotes intersubjectivity, and may help the patient deal with conflict in a non threatening manner that may circumvent defensive operations. PMID- 8486811 TI - Features of borderline personality and violence. AB - This study tested the hypothesis that borderline personality characterizes extreme violence by assessing features of borderline and schizotypal personality in three groups: Murderers, Violent, and Nonviolent adult offenders. Murderers had higher borderline personality scores than nonviolent offenders (p < .04). A test for linear trend indicated a linear increase in borderline scores with increasing degree of violence across the three groups (p < .02). No group differences were observed for schizotypal personality. Borderline traits associated with extreme violence consisted of unstable, intense relationships and affective instability. Group differences were not an artifact of group differences in age, social class, IQ, or number of previous custodies. It is concluded that borderline personality may predispose toward extreme forms of violence. PMID- 8486812 TI - Academic achievement in Substance-Abusing and Conduct-Disordered adolescents. AB - This study determined the influence of adolescent alcohol abuse on academic achievement. Substance Abusing (SA), Conduct Disordered (CD), and Normal Student Control (NSC) adolescents, stratified on Family History (FH) of alcoholism and gender, were tested on the Peabody Individual Achievement Test (PIAT). While SAs and CDs did not differ on the PIAT, both had lower subtest and total test standard scores than NSCs. FH + SAs did not differ from FH + CDs on the Spelling subtest, but both groups had significantly lower scores than FH - NSCs. For SAs and NSCs there were no significant correlations between measures of alcohol intake and PIAT subtest scores. PMID- 8486813 TI - Gender effects in diagnosing alcohol abuse and dependence. AB - Using a national population sample of 43,809 adults, male and female responses were compared for 41 indicators of alcohol abuse and dependence. While men reported all indicators more often than did women, the male to female ratio of positive responses varied according to both the construct represented by the item and its underlying prevalence. Items that might be construed as signs of weakness physical effects, psychological effects, and loss of control or powerlessness- had lower male/female ratios than other items. Excess male prevalence was greatest for the least prevalent indicators. The paper presents alternative interpretations of these findings and discusses their implications for diagnostic classification. PMID- 8486814 TI - Antidepressants and cancer: cause for concern? PMID- 8486816 TI - Acutely psychotic patients receiving high-dose haloperidol therapy. AB - Despite the trend towards lower neuroleptic dosing in the treatment of psychosis, there continue to be patients who are administered doses that are higher than recommended. Thirty-six acutely psychotic patients receiving parenteral haloperidol were evaluated by the Brief Psychiatric Rating Scale, the Schedule for Affective Disorders and Schizophrenia-Change Version, and the Nurses' Observation Scale for Inpatient Evaluation, as well as by drug levels in plasma. Patients were compared on the basis of total haloperidol dose in the first 24 hours: regular dose (RD: 10-30 mg) and high dose (HD: 40-80 mg). At baseline, patients in the HD group scored significantly higher on the Brief Psychiatric Rating Scale factor Hostile-Suspiciousness and the Nurses' Observation Scale for Inpatient Evaluation factor Irritability. Assignment to regular-dose and HD groups could not be accounted for on the basis of age, gender, weight, or duration of illness. Moreover, drug levels in plasma indicated that the HD patients did not require higher doses on the basis of differences in haloperidol levels. PMID- 8486815 TI - Differential effects of triazolam and ethanol on awareness, memory, and psychomotor performance. AB - Eight normal, healthy, male volunteers each received four triazolam doses (0, 2, 4, and 8 micrograms/kg) and four ethanol doses (0, 0.25, 0.5 and 1.0 g/kg) in a double-blind, double-dummy experiment in which within-subject dose sequence was determined by a balanced Latin square design. Triazolam and ethanol produced dose related and time-related effects on subject ratings of mood and perceived drug effects and objective measures of memory and psychomotor performance. Dose response curves for the two drugs were not parallel, and therefore, comparisons of the two drugs were based upon comparisons of the high dose of each drug. Although the two high-dose conditions generally were not different from one another, there were differences in their relative effect sizes, which were important. The high dose of each drug produced comparable degrees of impairment on two different psychomotor tasks. Triazolam, but not ethanol, produced significant impairment on two different memory tasks. The relative effects of each drug on subject ratings of mood and perceived drug effects varied across different subject-rated measures. Only ethanol significantly increased subject ratings of alcohol strength and feeling drunk. In comparison to ethanol, triazolam tended to produce less-pronounced subject ratings of drug effect magnitude, drug liking, and estimated performance impairment. However, less pronounced subjective effects of triazolam were not universally observed on all subject ratings. Triazolam produced greater effects on several sedative symptoms and produced comparable effects on several mood factor scales. PMID- 8486817 TI - Haloperidol dosing requirements: the contribution of smoking and nonlinear pharmacokinetics. AB - Previous data suggest the possibility that haloperidol daily dosing requirements may be confounded by smoking and, at higher doses, capacity-limited metabolism. Forty hospitalized patients suffering from an acute exacerbation of schizophrenia were treated for 2 weeks with fixed oral doses of haloperidol ranging from 10 to 70 mg/day (0.13 to 0.95 mg/kg/day) that produced mean steady-state concentrations between 4.5 and 55.4 ng/ml. No significant differences between the smoking and nonsmoking groups were obvious for the factors of weight, age, sex, daily doses, steady-state clearance, and steady-state haloperidol concentrations in plasma at week 1, week 2, and their mean. The hypothesis that the relationship between haloperidol dose and steady-state haloperidol concentration in plasma was affected by patients' smoking status and metabolic capacity was tested by multiple linear regression analysis and initially rejected. The relationship of dose to haloperidol concentration was fitted as a linear function. To improve the curve fit, the haloperidol concentrations and doses were transformed to their natural logs and then the regression line was refitted. The multiple regression analysis was repeated with the data in their transformed state. It was found that, although smoking status and dose of the drug did not independently affect the average haloperidol concentration, together they interacted in such a way that individual haloperidol concentrations were dependent on the smoking status at specific doses. Thus, two haloperidol dosing equations were generated, one for smokers and one for nonsmokers. PMID- 8486818 TI - Antidepressant-induced rapid cycling: six case reports. AB - We report six cases of rapid mood cycling induced by antidepressant treatment. The key to effective treatment involved the recognition of the pattern of apparent remission, relapse, antidepressant and/or stimulant adjustment, remission, relapse, etc. Hypomanic episodes were frequently mild and could be mistaken for remission. The destabilizing effects of antidepressant drugs were not corrected by the addition of mood stabilizers, necessitating the withdrawal of the antidepressant agent. All but one case responded to such withdrawal. Two cases required the addition of high-dose L-thyroxine for stabilization. Implications for an effective treatment protocol are discussed. PMID- 8486819 TI - This prescription may be hazardous to your health: who is accountable to the patient? PMID- 8486820 TI - Pimozide-induced depression? PMID- 8486821 TI - Neuroleptic malignant syndrome in communicating hydrocephaly and microcephaly. PMID- 8486822 TI - Effects of fluvoxamine on whole-blood serotonin and platelet number. PMID- 8486823 TI - Monoamine oxidase inhibitor hypertensive crisis headache and orthostatic hypotension. PMID- 8486824 TI - Response to "Monoamine oxidase inhibitors and hypertension". PMID- 8486825 TI - Rationale and clinical indications for contrast agents in MR imaging of the brain and spine. AB - This presentation explores clinical indications, limitations, and the scientific rationale for use of gadolinium contrast agents in MR imaging of the brain and spine. Enhancement of abnormal CNS tissues is related to structure and function of the blood-brain barrier under pathologic conditions, the prototype of which is tumor angiogenesis. Gadolinium administration can improve the diagnostic sensitivity of intracranial MR imaging, facilitating detection of leptomeningeal or ependymal disease spread and metastases. Moreover, use of contrast often provides greater diagnostic specificity by virtue of the presence and, in many cases, the absence of enhancement. This is particularly helpful in distinguishing metastases from other potential causes of high signal intensity on unenhanced spin-echo (SE) images. In addition to improving diagnosis of neoplasia, gadolinium use is often necessary to demonstrate most cranial neuropathies and to differentiate herniated disc from epidural fibrosis in the failed-back surgery syndrome. Advanced techniques that exploit gadolinium's properties (e.g., MR angiography, perfusion MR imaging) or increase its diagnostic effectiveness (e.g., fat suppression in the postoperative spine) are treated. PMID- 8486826 TI - Introduction to the gadolinium class. AB - Among the many paramagnetic substances, gadolinium ions [Gd(III)] exhibit one of the strongest degrees of proton-relaxation enhancement, which can be applied advantageously to selectively enhance diseases tissues on MR images. Such enhancement often proves the difference between suggestive and conclusive MR diagnostic studies. Chelation of the metal to organic ligands enhances safety and facilitates diagnostically useful tissue distribution and renal clearance. Chelates confer the further advantage of enabling gadolinium to be joined with carrier molecules, which can, in turn, foster tissue- or even antigen-specific targeting of contrast agents. Cost and relative biologic-tolerance profiles may prove to be key factors for distinguishing agents with similar distributions in clinical practice. PMID- 8486827 TI - Stability of gadolinium complexes in vitro and in vivo. AB - Gd(III) toxicity is such that, for in vivo use, the ion must be incorporated into stable, ionically bound complexes with organic chelating agents. Although metal chelate-based contrast agents have been demonstrated safe in phase I-III studies, their potential toxicities must be considered, particularly in the development of new contrast media. The potential for adverse effects is thought to arise from in vivo dissociation into constituent metal ion and ligand. Release of Gd(III) from ligand may also be facilitated by endogenous metals [e.g., Zn(II)] that compete with Gd(III) for ligand-binding sites. In vivo complex stability toward dissociation depends on several closely balanced characteristics of the metal and ligand that maintain metal-chelate integrity during residence in the body. Among design strategies explored to minimize the potential for in vivo Gd(III) release are the use of ligands that: form Gd(III) complexes with high thermodynamic stabilities; have binding selectivity for Gd(III) over endogenous metal ions; incorporate rigid cyclic structures and form Gd(III) complexes with greater kinetic stabilities than their open-chain homologs; or incorporate slight excess ligand to "scavenge" loosely bound or free endogenous metal ions that might otherwise compete with Gd(III) for ligand binding. PMID- 8486828 TI - MR imaging advances in practice. AB - Efficacy and safety of gadolinium contrast agents in MR imaging of the brain and spine are examined first in the context of clinical experience at the Barrow Neurological Institute. The role played by the absence and the presence of contrast enhancement in confirming or ruling out diagnostic suspicions is emphasized. Findings from multicenter phase I-III efficacy and safety studies of gadopentetate dimeglumine, gadodiamide, and gadoteridol in head and back imaging are reviewed. All three agents add diagnostic information, increase diagnostic confidence, and are extremely safe, readily tolerated compounds exhibiting generally mild side-effect profiles. Gadolinium-enhanced MR scanning is placed in the longer perspective of diagnostic imaging strategies, to consider the assignment of priorities to various modalities according to the suspected disease at hand. PMID- 8486829 TI - Future uses of MR imaging agents. AB - Existing paramagnetic agents and novel superparamagnetic pharmaceuticals under development promise to advance substantially the frontiers of MR imaging. Used in conjunction with ultrafast MR techniques, such as echoplanar imaging and turboFLASH (fast low-angle shot), relaxivity agents (e.g., dysprosium, gadolinium), which alter T1 characteristics of tissue protons they act on, can be used to generate quantitative maps of dynamic blood-brain barrier permeability as well as regional hemodynamic profiles of diseased heart and other organs. In addition, the magnetic susceptibility (T2*)-altering effects of gadolinium can be exploited to map regional cerebral blood volume during task-activated and pathologic brain states. Magnetic susceptibility agents, such as monocrystalline iron oxide nanoparticles (MIONs), allow the advantages of scintigraphy to be joined with the high spatial resolution of MR imaging. Not only can these magnetopharmaceutical preparations serve as hemodynamic markers, they have already enabled function-specific imaging at the cellular level under diverse pathologic conditions. PMID- 8486830 TI - Economic/reimbursement issues in MR imaging with gadolinium contrast agents. AB - Implementation of an accurate, reliable index of cost effectiveness would help to advance technology assessment and reimbursement of MR imaging procedures, including gadolinium enhancement. To this end, an objective, consensual measure that satisfies the need for "gold-standard" confirmation of diagnostic impressions in routine clinical practice and limits interpreter bias has been developed. Eponymously termed Diagnostic Merit, this barometer is expressed as the percentage of independent judges confirming diagnostic impressions entered by case-blinded radiologists assigned unenhanced and enhanced image sets for interpretation. The judges, who are informed of clinical indications, clinical follow-up, and unblinded diagnostic interpretation of the MR scans, confirm only those case-blind interpretations deemed "close enough for diagnostic utility" to actual clinical profiles. According to this method, gadopentetate dimeglumine has been shown to be cost effective by promoting optimal diagnostic performance. This improvement in utility offsets the cost of the gadolinium contrast agent. Efficacies of gadodiamide and gadoteridol, two other contrast agents in development, have been demonstrated by other measures but are probably also evaluable through the Diagnostic Merit method. CPT-4 codes for contrast-enhanced MR imaging are reviewed. PMID- 8486831 TI - Clinical experience with gadolinium contrast agents in spinal MR imaging. AB - Gadolinium contrast agents represent one of the most important advances in MR imaging of spinal disease. Many abnormalities that affect the epidural, intradural extramedullary, and intramedullary compartments demonstrate contrast enhancement, the pattern of which often provides specific diagnostic information. This is particularly true of neoplastic diseases such as primary glioma and leptomeningeal tumor spread. Gadolinium contrast also finds vital application in differentiating herniated disc from epidural fibrosis in the failed-back surgery syndrome, as well as hypointense disc from enhancing tumor in select cases. Certain demyelinating and inflammatory processes also have predictable MR manifestations that facilitate accurate diagnosis. PMID- 8486832 TI - Effects of recombinant bovine somatotropin (sometribove) on ovarian function in lactating and nonlactating dairy cows. AB - Metabolic and ovarian responses of lactating and nonlactating cows to recombinant bST (sometribove) were measured. Eighteen lactating cows (60 to 100 d postpartum) and 6 nonlactating cows (> 400 d postpartum) were injected daily with bST or saline during one of two periods. Concentrations of hormones and metabolites were measured in plasma, and ultrasonography was used to quantify ovarian follicular growth. Concentrations of glucose, insulin, IGF-I, progesterone, and estradiol in plasma were greater in nonlactating cows than in lactating cows. Lactating cows had fewer class 2 (6- to 9-mm) and class 3 (10- to 15-mm) follicles and more class 4 (> 15-mm) follicles than nonlactating cows. Bovine somatotropin increased the numbers of follicles in lactating cows so that the numbers of class 2 and of class 3 follicles were equivalent to those for non-lactating cows. Sizes of the largest follicles were similar for bST-and saline-treated cows. The second largest ovarian follicles, however, were larger in bST-treated cows. Ovarian follicular dynamics were altered by bST and lactation. Bovine somatotropin increased the numbers of follicles (6 to 15 mm) in lactating cows and size of second largest ovarian follicles in both lactating and nonlactating cows. Lactating cows developed dominant follicles that were larger and less estrogenic than those of nonlactating cows. PMID- 8486834 TI - Survival of bull spermatozoa seeded and frozen at different rates in egg yolk tris and whole milk extenders. AB - Six factorially arranged experiments were designed to study effects of seeding, freezing, and thawing rates in whole milk and egg yolk-Tris extenders commonly used for commercial cryopreservation of bull sperm. In these extenders, semen normally is supercooled to -13 or -14 degrees C unless the sperm are seeded. When sperm were supercooled or seeded, either mechanically or with immobilized silver iodide, and frozen to -196 degrees C, the postthaw percentages of motile sperm were 59, 57, and 64%, respectively. Freezing rates of -15, -25, and -35 degrees C/min gave similar sperm survival rates and were superior to -5 degrees C/min. For milk, the critical freezing temperature extended to -75 degrees C before transfer to liquid nitrogen gave good results. For egg yolk-Tris extender, transfer to liquid nitrogen was less critical once -50 degrees C had been attained. Thawing of sperm in water baths at 25 and 45 degrees C gave similar results, and both temperatures were superior to 5 degrees C. The postthaw percentage of motile sperm in egg yolk-Tris was equal or superior to that of sperm frozen in milk. A freezing rate of -15 degrees C/min to -100 degrees C and thawing at 25 degrees C consistently gave good results. PMID- 8486833 TI - Ovarian follicular populations in lactating dairy cows treated with recombinant bovine somatotropin (sometribove) or saline and fed diets differing in fat content and energy. AB - Interactions of dietary energy and fat with recombinant bST (sometribove) injections were tested for their effects on ovarian function. Lactating dairy cows were fed one of three diets differing in energy concentration (NEL) and percentage of DM of calcium salts of long-chain fatty acids: diet 1, 1.68 Mcal/kg and 0%; diet 2, 1.68 Mcal/kg and 2.2%; and diet 3, 1.78 Mcal/kg and 2.2%. Cows were injected daily with bST or saline during one of two 19-d interestrous periods (crossover design) in which ovarian follicles were measured by ultrasonography. The bST-treated cows produced more FCM and were in lower energy balance than saline-treated cows. Before d 12 (first follicular wave, estrus = d 0), bST-treated cows had more ovarian follicles in classes 1 (3 to 5 mm; cows on diet 3) or 2 (6 to 9 mm; cows on diets 1 and 2) than saline-treated cows. After d 12 (preovulatory follicular wave), numbers of follicles in different size classes were similar for bST-treated and saline-treated cows, but cows fed diet 2 had larger preovulatory follicles. Lower dietary energy and bST treatment were both associated with larger subordinate follicles. Ovarian follicles less than 10 mm were stimulated by bST, and calcium salts of long-chain fatty acids increased diameters of preovulatory follicles. PMID- 8486835 TI - Prevalence of high somatic cell counts in bulk tank goat milk. AB - Higher SCC have been observed in goat milk than in cow milk. This study evaluated the prevalence of high SCC and determined whether increased neutrophils were a factor in high SCC. Bulk tank goat milk samples were collected from commercial dairy goat herds in California, Arkansas, Michigan, and Wisconsin. Total SCC were determined using a Fossomatic Electronic Cell Counter and microscopically using pyronin Y-methyl green stain. Differential counts were determined using Wright's stained cytospin centrifuge preparations. Average SCC were high (6.12 log10 cells/ml; geometric mean, 1.32 x 10(6) cells/ml). The average of the Fossomatic and direct microscopic SCC indicated that 8.6% of the producers had SCC < .75 x 10(6) cells/ml and that 34.5% were < 1 x 10(6) cells/ml. The current goat milk SCC standard is 1 x 10(6) cells/ml; the cow milk SCC standard will be .75 x 10(6) cells/ml in 1993. Milk samples contained 9.9% macrophages, 2.8% lymphocytes, and 87% neutrophils. These data indicate that high SCC were prevalent and that increased neutrophils contributed to high SCC in the bulk tank goat milk. PMID- 8486836 TI - Teat tissue reactions to milking: effects of vacuum level. AB - Machine-induced changes in diameter, thickness, and compressibility of the teat apex and teat barrel were measured on all teats of four cows milked at vacuums of 25, 30, 40, and 50 kPa. Measurements were made with an electronic caliper instrument immediately before milking and then at .5, 15, and 30 min after milking. Teat length was also measured at these times. Immediately after milking, for the two higher levels, teats were significantly thicker (7 to 10% thicker at 40 kPa, 17 to 25% at 50 kPa), shorter (by 3 to 6 mm), smaller in diameter (by 2 to 4 mm for the apex, 3 to 6 mm for the barrel), and less compressible for all milking treatments compared with the premilking status for individual teats. Although teat thickness recovered to the premilking mean values 30 min after milking at 40 or 50 kPa, the barrel still was significantly thicker after 30 min compared with those at the lower vacuum treatments. We suggest that changes in teat length, diameter, thickness, and compressibility after milking at low vacuum levels mainly reflect tissue responses to udder evacuation. In contrast, increased teat wall thickness and reduced compressibility of teat tissue at higher vacuum levels likely result mainly from machine-induced edema. PMID- 8486837 TI - Use of bovine rib bone in serial sampling for mineral analysis. AB - A total of 2160 samples of rib bone were used in a split-plot design analysis of variance to show that, on an ash weight basis, P content is not different among the right and left 9th, 10th, 11th, and 12th ribs of cattle above 6 mo of age. Results were similar for Ca on a fresh or dry weight basis. Some differences existed in Mg content among some of the ribs. Location on the rib from which samples were taken was responsible for significant differences in mineral concentrations. Based on results reported herein, ribs 9, 10, 11, and 12 of the right and left side may be used in the serial sampling of bone tissue in the bovine for the purpose of comparing the content of P, Ca, and--to some extent- Mg. Serial sampling makes possible comparison of bovine mineral status based on bone tissue over an extended experimental period that includes eight sampling dates. PMID- 8486838 TI - Computerized monitoring of gas production to measure forage digestion in vitro. AB - The techniques reported in this paper were developed to facilitate the study of the kinetics of forage digestion in vitro by measuring gas production. Fiber disappearance as a measure of the reaction rate has been replaced by the use of computerized pressure sensors to monitor the gaseous products (CO2, CH4) of microbial metabolism. The recording system described requires a computer, pressure sensors, an interface card, and appropriate software to monitor gas production continuously. Several variables, including sample size, inoculum size, vessel size, and type of pressure sensor, have been investigated to determine ranges within which gas production can be measured accurately, and the reproducibility of the results has been established. Because this technique uses small (100-mg) samples, a modified NDF method has been introduced that allows determination of extent of digestion at the end of an incubation in which gas production has been monitored. A strong linear relationship existed between NDF disappearance and gas production. PMID- 8486839 TI - In vitro effects of a thiopeptide and monensin on ruminal fermentation of soluble carbohydrates. AB - Using a purified diet and a mixed culture of ruminal microorganisms, we studied the in vitro effects of a sulfur-containing peptide (A10255) and monensin on ruminal VFA and lactic acid concentrations. After 22 h of fermentation, total VFA concentration was greater in cultures with A10255 and monensin (2.5 ppm each) than in untreated controls (84.1, 91.9, and 65.2 mM for cultures with A10255, monensin, and control, respectively). The molar proportions of propionate were more than 40% greater, and the molar proportions of acetate were about 15% less, in treated than in untreated cultures. The molar proportions of the remaining VFA were lowest in monensin-treated cultures, intermediate in A10255-treated cultures, and greatest in untreated cultures. Addition of A10255 or monensin also prevented the accumulation of lactate and maintained higher pH than in untreated cultures. In pure culture, growth of Streptococcus bovis was slowed by A10255 at pH 5.5 and 6.5. Growth of S. bovis was reduced markedly with addition of monensin at pH 6.5 and inhibited at pH 5.5. Growth of Lactobacillus acidophilus was inhibited more at pH 5.5 than 6.5 with monensin but was unaffected by A10255. The thiopeptide A10255 and monensin inhibited ruminal lactate production, but sensitivities of lactate-producing bacteria differed between compounds. PMID- 8486840 TI - Effect of increasing ruminal butyrate on milk yield and blood constituents in dairy cows fed a grass silage-based diet. AB - The effects of increased ruminal supply of butyrate on milk yield, milk composition, and blood metabolites were studied in four lactating cows in a 4 x 4 Latin square design. The basal diet comprised grass silage, hay, and concentrate (34:22:42, DM basis) and was supplemented with isoenergetic VFA infusions (3.58 Mcal/d). A 3:1 molar mixture of acetate and propionate was replaced gradually with butyrate at the rates of 0, 200, 400, or 600 g/d. When the amount of infused butyrate increased, isobutyrate, butyrate, and isovalerate in plasma and acetoacetate and beta-hydroxybutyrate in whole blood increased linearly, but plasma glucose concentration decreased. The latter was associated with a trend toward higher plasma urea concentration, suggesting that more AA were used for gluconeogenesis as the supply of propionate decreased and that of butyrate increased. Milk yield was not changed. The concentrations of milk fat and protein increased, and that of lactose decreased linearly, with the rate of butyrate infusion. Milk fat yield increased, and lactose yield tended to decrease, with increased butyrate infusion. These results indicate that changes in the supply of butyrate do not affect markedly milk yield in cows yielding less than 20 kg/d but cause marked changes in milk composition. The increase in ruminal butyrate supply increased ketogenesis and decreased gluconeogenesis in the liver of lactating dairy cows. PMID- 8486841 TI - Dose titration of sustained-release recombinant bovine somatotropin in lactating dairy cows. AB - Lactating dairy cows (n = 264) were used in seven dose titration experiments at four geographic locations in the United States. A sustained-release formulation of recombinant bST was evaluated for a 30-wk treatment period that began 14 wk postpartum. The first series of four experiments evaluated doses of 0, 140, 350, or 700 mg of bST/14 d (series A); the second series evaluated doses of 0, 56, 140, or 350 mg of bST/14 d (series B). Milk yield, DMI, milk composition, body condition, health, and reproductive parameters were measured. Multiparous cows in series A that were administered 700 mg of bST/14 d yielded 3.0 kg/d more milk and 3.5% FCM than control cows. When all seven experiments were combined, multiparous cows that were administered 350 mg of bST/14 d yielded 2.7 and 2.6 kg/d more milk and 3.5% FCM than control cows. Dry matter intake was not significantly affected by bST administration. In series A, an increase in milk yield with no increase in DMI resulted in lower adequacy of dietary NEL and CP to meet maintenance and yield requirements among multiparous cows administered 700 mg of bST/14 d. Primiparous cows that were administered bST in series A and both parity groups in the combined seven experiments were not different from control cows in the adequacy of dietary NEL or CP to meet maintenance and yield requirements. No adverse effects of bST on health parameters were significant, and doses of 350 mg of bST/14 d or less caused no changes in reproductive parameters. Conception rate was decreased by administration of 700 mg of bST/14 d. These data suggest that 350 mg of bST/14 d increased yields of milk and FCM with no adverse effects on DMI, health, or reproduction in dairy cows. PMID- 8486842 TI - Individual variation in the composition of colostrum and absorption of colostral antibodies by the precolostral buffalo calf. AB - The total protein and Ig content in the first colostrum was higher in buffalo cows than in dairy crossbred cows. Individual variation in Ig content of first colostrum may be responsible for differences in susceptibility of calves to infections. The decline in Ig content during subsequent milkings was faster in dairy crossbred cows. The major class was IgG in both species. Absorption of colostral proteins and Ig was 14.0 g (68%) and 4.6 g (75.4%), respectively, within 1 h of feeding colostrum to a 7-h-old female buffalo calf. Absorption was decreased to 2.1 and .83 g/h after the first feeding, suggesting that the intestinal absorption of macromolecules declined 1 h after the first feeding. Marginal placental transfer of maternal Ig also was demonstrated in buffalo. An albuminlike protein was predominant in blood plasma of the precolostral buffalo calf. This protein decreased, and IgG in blood plasma increased, after colostrum was fed, indicating that albuminlike protein may be involved in the transfer of maternal nutrients to the fetus. PMID- 8486843 TI - The goals and status of the bovine gene map. AB - The bovine genome map has developed rapidly in recent years. The synteny and chromosomal maps are sufficiently developed to identify chromosomal conservation with other mammals, which is especially useful for the extrapolation of data to cattle from the better developed maps of mouse and human. The rapid development of microsatellite and other hypervariable markers in several laboratories around the world and the availability of a common set of reference families for linkage analysis will produce a 20-cM map in 2 yr. Immediate needs for development are 1) markers to anchor physical maps to linkage maps, 2) resource families segregating economic trait loci, and 3) chromosome-specific libraries to develop densely saturated linkage maps over genomic regions shown to contain economic trait loci. PMID- 8486844 TI - Three-dimensional molecular modeling of bovine caseins: an energy-minimized beta casein structure. AB - To obtain a molecular basis for the similarities and dissimilarities in the functional, chemical, and biochemical properties between beta-casein and the other caseins, a predicted three-dimensional model is presented. The predicted structure was assembled using molecular modeling techniques, as well as secondary structural prediction algorithms, in conjunction with global secondary structural information from Raman spectroscopy. To add validity to this model, the structure was refined using energy minimization techniques to diminish the likelihood of structural overlaps and energetically unfavorable van der Waals contacts arising from the large number of proline residues present in the beta-casein sequence. The refined model overall showed a loosely packed, asymmetrical structure with an axial ratio of 2:1. Hydrophobic side chains were uniformly dispersed over one end (C terminal) and the center surface of the structure; the other end (N terminal) was hydrophilic. The hydrophobic section also possessed a large loop through which water could easily travel. Such a suprasurfactant structure could account for the micellar type of hydrophobically driven self-association exhibited by beta-casein. Other chemical and biochemical data are in good agreement with the refined structure. PMID- 8486845 TI - Separation and characterization of the C-terminal half molecule of bovine lactoferrin. AB - The C-terminal half molecule (C lobe) of bovine lactoferrin was isolated by mild tryptic hydrolysis of lactoferrin followed by gel filtration and ion-exchange chromatography. The identity of the fragment was established by determining its N terminal and C-terminal amino acid sequences and comparing them with the amino acid sequence of intact lactoferrin. The isoelectric point of the C lobe ranged between pH 6.2 and 6.5 as measured by isoelectric focusing on polyacrylamide gels. The circular dichroic spectrum in the range of 250 to 350 nm of the C lobe differed slightly from that of intact lactoferrin. The pattern of lectin reactivity was similar for both the C lobe and intact lactoferrin. The C lobe showed partial antigenic identity with intact lactoferrin as demonstrated by the double immunodiffusion method, and pH dependence of iron binding of C lobe is the same as that of intact lactoferrin molecule. PMID- 8486846 TI - Relationship among bile tolerance, bile salt deconjugation, and assimilation of cholesterol by Lactobacillus acidophilus. AB - The relationships among growth in the presence of bile, deconjugation of sodium taurocholate, and assimilation of cholesterol by 19 cultures of Lactobacillus acidophilus were examined. Cultures of L. acidophilus were grown at 37 degrees C in lactobacilli MRS broth supplemented with sodium thioglycollate, sodium taurocholate, and cholesterol (cholesterol phosphatidyl choline micelles). Deconjugation activity was maximum in the late exponential phase of growth, which also coincided with maximum assimilation of cholesterol. Considerable variation existed among cultures in their ability to grow in the presence of bile, to deconjugate sodium taurocholate, and to assimilate cholesterol. However, statistical analyses revealed no significant correlations. PMID- 8486847 TI - Growth characteristics of bifidobacteria in ultrafiltered milk. AB - Five replicates of raw skim milk were ultrafiltered at 54 degrees C to total protein concentration ratios of 2:1, 3:1, 4:1, and 5:1. Bifidobacterium bifidum and Bifidobacterium longum were inoculated at 5% into skim milk that was not ultrafiltered (1:1) and into ultrafiltered skim milks followed by incubation at 37 degrees C. The mean maximum bacterial count (colony-forming units per milliliter) range and protein concentration ratio were from 6.25 x 10(8) to 1.69 x 10(9), skim milk; 4.42 x 10(8) to 3.56 x 10(9), 2:1; 2.62 x 10(8) to 3.94 x 10(9), 3:1; 6.67 x 10(8) to 1.88 x 10(9), 4:1; and 2.90 x 10(9) to 3.59 x 10(9), 5:1. The mean developed acidity at maximum B. bifidum population in skim milk was .16%, and pH was 5.55. The 5:1 concentrate had a higher mean developed acidity of .57% at pH 5.35, which was similar to that of the skim milk. Trends were similar for B. longum. Because of the increased buffering capacity of highly concentrated ultrafiltered milks, pH 5.5 or higher was maintained longer, along with high developed acidity. Scanning electron micrographs showed distinct morphological variations between bifidobacteria grown in broth versus those grown in the milks. PMID- 8486848 TI - Growth of Listeria monocytogenes and Clostridium sporogenes in cottage cheese in modified atmosphere packaging. AB - Low fat cottage cheese (pH 5.14) was inoculated with three strains of Listeria monocytogenes, serotypes 1a and 4b, an isolate from a dairy processing plant, and Clostridium sporogenes ATCC 3584. The cheese was packaged with or without added dissolved CO2 in polystyrene tubs overwrapped with or without high barrier heat shrink film and stored at 4, 7, and 21 degrees C for up to 63 d. The concentration of CO2 in the container headspace was 35% (vol/vol). The CO2 concentration in that headspace declined by one-third over the 63 d of storage at 4 degrees C. Clostridium sporogenes failed to grow under any condition applied in this study. In the conventionally packaged cottage cheese, L. monocytogenes increased from 10(4) to 10(7) cfu/g after lag phases of 28 and 7 d at 4 and 7 degrees C, respectively. In contrast, L. monocytogenes failed to grow in cottage cheese packaged with CO2 and stored at 4 degrees C up to 63 d and increased from 10(4) to 10(5) cfu/g in products packaged with CO2 at 7 degrees C. These data suggest that the addition of CO2 to cottage cheese to extend shelf-life does not represent an increased Listeria or botulism hazard but that cottage cheese could be a vehicle for listeriosis. PMID- 8486849 TI - Growth responses of coliform bacteria to recombinant bovine cytokines. AB - Growth responses of 10 coliform isolates to recombinant bovine cytokines were measured in vitro. Six Escherichia coli and four Klebsiella pneumoniae isolates obtained from bovine IMI were tested for growth responses to recombinant bovine interleukin-1 beta, interleukin-2, and interferon-gamma. Cytokines were tested at 10(4), 10(3), 10(2), and 10 U/ml of media. Media used were a synthetic tissue culture medium, a chemically defined synthetic bacterial growth medium, and UHT sterilized milk. Bacterial counts in the synthetic tissue culture medium and UHT milk increased slightly as concentration of interferon-gamma in the media increased. Recombinant bovine interferon-gamma increased bacterial populations during the log growth phase but did not affect the number of bacteria in stationary growth phase. Bacterial growth responses were not related to either interleukin-2 or interleukin-1 beta concentrations in any of the three media. Bacterial growth responses to cytokines were not related to differences in either serum susceptibility, growth of isolates in dry cow secretion, duration of IMI from which isolates were obtained, or bacterial species. PMID- 8486850 TI - Influence of recombinant bovine somatotropin (sometribove) on mononuclear cells during the nonlactating period. AB - Recombinant bST was evaluated as a potential immunoenhancer of bovine peripheral blood and mammary gland mononuclear cells during the nonlactating period. Cows (n = 4 per group) were assigned to one of four treatments: 1) untreated, 2) treated with recombinant bST during lactation only, 3) treated with recombinant bST during the nonlactating period only, and 4) treated with recombinant bST during lactation and the nonlactating period. Recombinant bST treatment during the nonlactating period had no effect on proliferation of bovine blood or mammary gland mononuclear cells in response to stimulation by mitogens or allogeneic cells. Recombinant bST treatment during the nonlactating period enhanced interleukin-2 secretion by mononuclear cells isolated from cows treated also with recombinant bST during lactation. However, recombinant bST treatment during the nonlactating period had little effect on interleukin-2 secretion by mononuclear cells from cows not treated with recombinant bST during lactation. Results of this study suggest that recombinant bST alters effector functions rather than proliferation of bovine mononuclear cells. PMID- 8486851 TI - Effect of prepartum bovine somatotropin in primigravid ewes on mammogenesis, milk production, and hormone concentrations. AB - Twenty-five primigravid ewes were used to investigate the effect of bST, between 97 and 124 d of gestation, on mammogenesis and subsequent milk production. Five ewes (reference group) were slaughtered at 96 d of gestation, and the remaining ewes were injected daily with saline (control group: n = 10) or .1 mg/kg of BW of bST (bST group: n = 10). Following bST treatment, 5 control and 5 bST group ewes were slaughtered (slaughter group). The remaining ewes were slaughtered after lambing and being milked for 8 wk (production group). Weekly blood samples were obtained from both slaughter and production group ewes. Slaughter group ewes were also subjected to 8-h serial blood sampling at 98 d (period 1) and 123 d (period 2) of gestation. Milk production was 42% higher in ewes treated prepartum with bST than in those treated with saline. Results suggest that the increase in milk was due to an increase in mammary parenchymal cell number rather than to an increase in cellular activity. The high rate of [3H]thymidine incorporation into parenchymal tissue in reference group ewes suggests that the increase in parenchyma during the second trimester of gestation is due to cellular hyperplasia but that cellular hypertrophy may be more important during the last trimester. Plasma IGF-I concentrations were significantly higher during bST treatment and remained elevated between daily injections; the increase was greatest in period 2. PMID- 8486852 TI - Evaluation of mandibular infiltration versus block anesthesia in pediatric dentistry. AB - The authors consider mandibular infiltration as a possible alternative to mandibular block anesthesia in young children. The study sample comprised eighteen children ages six to nine years old who required bilateral identical treatment on primary mandibular molars. A random number table was used to determine which side of the mouth was to receive the block or the infiltration technique and a coin toss determined which would be administered first: A short 27 gauge needle was used to inject a 2 percent lidocaine solution with 1:100,000 epinephrine, in both techniques. The paired t-test indicated no significant difference between the two techniques for any of the factors evaluated. PMID- 8486853 TI - Electrosurgical pulpotomy: a retrospective human study. AB - While the formocresol pulpotomy has enjoyed long-term clinical use and success, concerns over its toxicity and mutagenicity have prompted research into other pulpotomy techniques. The purpose of this study was to observe retrospectively the results of the electrosurgical pulpotomy technique used on primary molar teeth requiring pulp therapy, secondary to carious involvement. The mean age at the time of treatment was 5 years, 11 months and the mean postoperative observation time was 2 years, 3 months. Of the 164 teeth studied, 127 were normal at the last observation visit; 32 had undergone exfoliation; 4 had an abnormality associated with the pulpotomized tooth, but were not considered failures; and 1 was considered a failure. This is a 99.4 percent success rate. Compared to a formocresol pulpotomy study of similar design, the success rate for the electrosurgical pulpotomy procedure in this study is higher at the statistically significant level of p < 0.01. PMID- 8486854 TI - A review of fluoride intake from fluoride dentifrice. AB - Ingestion of fluoride dentifrice by preschool children recently has been identified as a risk factor for dental fluorosis. There are relatively few published studies concerning patterns of fluoride dentifrice use and ingestion among preschool children at greatest risk for dental fluorosis. This paper reviews the literature on dentifrice use and ingestion in an attempt to emphasize to the practitioner the potential importance of this fluoride exposure in fluorosis etiology. PMID- 8486855 TI - Dental management of the child and adolescent with major depression. AB - Major depression is a psychiatric disorder in which mood, thought content, and behavioral patterns are impaired, often for an extended period of time. This condition appears to have an increasing prevalence among young children and adolescents. It may be associated with a disinterest in performing appropriate preventive oral hygiene techniques, a cariogenic diet, rampant dental decay, and advanced periodontal disease. Appropriate dental management necessitates a vigorous preventive dental education program and special precautions when administering local anesthetics and prescribing sedative and analgesic medications. PMID- 8486856 TI - The poisoning of our children. AB - In the second half of the 1980s, almost four million exposures to poison were reported for children less than six years of age. The causes, types of poisoning and treatment are reviewed. PMID- 8486857 TI - Is your next pediatric patient an addict? AB - There have been decreases in the use of illicit drugs by youngsters in our country. However, the reality is that great numbers of children continue to use these substances. A review is provided of the use of illicit drugs by children. In addition, the consumption of alcohol and cigarettes by youngsters also is considered. PMID- 8486858 TI - Gender trends among specialists in pediatric dentistry. AB - The number of women entering the dental profession has increased over the past few years and the percentage of females enrolling in pediatric postdoctoral studies surpassed 50 percent in 1990. The impact of the shift in the gender of practicing pediatric dentists was examined in this study. A survey was designed to evaluate the relationship between the age and gender of the pediatric dentist, location of principle practice site, and the number of hours dedicated to direct patient care. Twenty-seven hundred and sixty surveys were mailed to pediatric dentists in the United States and 1246 were returned (46 percent). Significantly more males were in private practice than females, although the difference in percentages was small (85 percent versus 80 percent). Women identified universities, hospitals, and institutions as their principle site of practice significantly more often than males (20 percent versus 15 percent). On average, females in private practice work only slightly fewer hours per week providing patient care than do males (32 versus 35 hours/week). In university, hospital, and institution, settings the reverse is true: women spend more time in direct patient care than men (27 versus 23 hours/week). PMID- 8486859 TI - Adverse reaction to a fissure sealant: report of case. AB - A six-year-old girl with a known allergy to mites had her first permanent molars sealed with Delton. On the night of the treatment day, she began to have asthmatic trouble. Urticaria appeared a few days later. Treatment with cortisone gave no relief. When the fissure sealant material was taken away, the asthma and urticaria disappeared. Possible explanations to the reaction are discussed in the report. PMID- 8486860 TI - Adolescent rebellion. PMID- 8486861 TI - A restorative dentistry renaissance for children: light-hardened glass ionomer/resin cement. AB - The light-hardened glass ionomer/resin dental restorative material was introduced in 1992. Its formula includes 80 percent glass ionomer material combined with a 20 percent visible light polymerized resin component. The authors have completed over 1300 class I, class III, and class V restorations in primary teeth, using the new material. The new material is considered by the authors to be a great improvement over the self-hardening glass ionomers. The addition of the 20 percent light-hardened resin component to the glass ionomer formula gives the material an initial setting time under sixty seconds, and improves resistance to wear and fracture. PMID- 8486862 TI - Prevalence of postoperative sensitivity with indirect Class II resin composite inlays. AB - In this clinical trial, the prevalence of postoperative sensitivity is studied in a comparison of standard size indirect class II resin composite inlays with class II amalgam restorations. Fifteen percent of the 240 restored teeth (resin composite and amalgam restorations) showed some form of sensitivity, the majority of them of a passing nature. No difference was found between amalgam and composite restorations. Molars appear to show more complaints than premolars and, rather than the restorative material applied, the patient seems to determine the results. Differences in prevalence of sensitivity between direct resin composite restorations in a previous study and the indirect restorations are discussed, using among others the differences in sensitivity that were found between the amalgam-control restorations of both studies. PMID- 8486863 TI - The relationship between alveolar bone loss and proximal caries in children: prevalence and microbiology. AB - The present study describes the prevalence of alveolar bone loss (ABL) in children in relation to caries, contact and space loss. In addition, the microbial composition of the subgingival plaque of 20 sites, from 5 children, is presented. Bite-wing radiographs from 500 children were examined. ABL was evident in: 99 sites from 60 children; > 1 site in 27 children; the maxilla only in 34 children; the mandible only in 17 children; both arches in 9 children; 37 sites with no caries; 4.9 percent of all sites with proximal caries; 15.8 percent of all sites with contact loss; and 20.5 percent of all sites with mesial drift. Anaerobic bacteria were cultured from all 20 sites. No significant differences in the percentages of colony forming units of Actinobacillus actinomycetemcomitans and black pigmented Bacteroides were found among sites with/without bone loss, with/without caries or probing depths smaller/equal or larger than 2.5 mm. PMID- 8486864 TI - Oxygen consumption after cardiopulmonary bypass--implications of different measuring methods. AB - OBJECTIVE: To determine whether intra-pulmonary oxygen consumption or whole body oxygen consumption is the main determinant of the hypermetabolic response after cardiopulmonary bypass. Secondly, which method of measuring oxygen consumption best quantifies this hyperdynamic response. DESIGN: We measured oxygen consumption by analysing respiratory gas (VO2-gas), carbon dioxide excretion (VCO2), and respiratory exchange ratio (RER = VCO2/VO2), and calculated oxygen consumption using the Fick-method (VO2-Fick) and intra-pulmonary oxygen consumption (VO2-gas - VO2-Fick) in patients at fixed times before and after elective cardiac surgery. Next, comparisons were made between methods and also between measurements at different times before and after bypass. SETTING: University hospital. PATIENTS: 10 elective cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: VO2-gas, VCO2 and RER were measured with an open circuit indirect calorimeter. VO2-Fick was calculated: VO2 Fick = cardiac index x (arterial - mixed venous oxygen content). Intrapulmonary oxygen consumption was calculated as the difference between VO2-gas and VO2-Fick. Both VO2-gas and VO2-Fick were about 20% higher after bypass than after induction of anaesthesia. Absolute values of VO2-gas were about 30% higher than VO2-Fick. Intra-pulmonary oxygen consumption accounted for 32% of whole body oxygen consumption after induction of anaesthesia and did not increase after bypass. CONCLUSION: Whole body oxygen consumption and not intra-pulmonary oxygen consumption is the main determinant of the hypermetabolic response after bypass. Increased intra-pulmonary oxygen consumption is not related to bypass. VO2-gas best quantifies this hypermetabolic response directly after bypass, and not VO2 Fick, VCO2 or intra-pulmonary oxygen consumption, since VO2-Fick excludes intra pulmonary oxygen consumption and VCO2 does not reflect metabolism directly after bypass. PMID- 8486865 TI - Rapid recovery of acquired purpura fulminans in a patient with familial C4bBP deficiency. AB - A 32-year-old pregnant woman developed meningococcemia associated purpura fulminans and quickly improved with therapy. After this disease C4b-Binding Protein (C4bBP) plasma levels remained very low while protein S activity was in the normal range. Familial investigation proved a hereditary C4bBP deficiency. This observation points out the role of the protein C-protein S system during acquired purpura fulminans. PMID- 8486866 TI - Basic concepts and fundamental issues in technology assessment. PMID- 8486867 TI - Theophylline intoxication: toxicokinetic evaluation of hemodialysis. PMID- 8486868 TI - Low pulmonary compliance and/or tachycardia may reduce arterial pressure variations despite hypovolemia. PMID- 8486869 TI - Inhalation of a minitracheostomy tube. PMID- 8486870 TI - Neonatal and pediatric intensive care--a new section in Intensive Care Medicine. PMID- 8486871 TI - Newborn extracorporeal lung assist using a novel double lumen catheter and a heparin-bonded membrane lung. AB - We report the clinical application of a novel double lumen catheter for veno venous extracorporeal lung assist (ECLA) and the use of a heparin-bonded hollow fiber membrane lung, in the treatment of newborn respiratory failure. The outer lumen of the double lumen catheter was 14 Fr and was used for blood drainage; while the inner 8 Fr catheter was used for blood return. The double lumen catheter was made of spiral wire reinforced polyurethane, with a wall thickness of 0.25 mm. The hollow fiber membrane was made of non-microporous polyolefin, and was not permeable to water or plasma. We used this system to treat a newborn patient with meconium aspiration syndrome. Heparin was infused continuously at a rate of 18-25 units/kg/h, equal to 1/3 of the usual amount when a non-heparin bonded ECLA system was used and maintaining the activated clotting time near 120 s. Bleeding from cutdown sites was negligible. Only the right internal jugular vein was sacrificed. The patient was successfully weaned from ECLA and appears normal one year following discharge. PMID- 8486872 TI - Sudden death revealing Chiari type 1 malformation in two children. AB - We report the first two fatal cases of sudden unprovoked cardiorespiratory arrest in children with previously undiagnosed Arnold-Chiari type 1 malformation. This diagnosis should be considered in children with unexplained cardiorespiratory arrest. The risk of sudden death in Arnold-Chiari type 1 malformation reinforces the indication for early neurosurgical procedure. PMID- 8486873 TI - Relief of severe pulmonary hypertension after closure of a large ventricular septal defect using low dose inhaled nitric oxide. AB - A 16-month-old girl developed severe pulmonary hypertension after closure of a large ventricular septal defect. All conventional therapeutic measures failed; an attempt to add nitric oxide at a continuous low dose to the inspired gas allowed resolution of pulmonary hypertension and low cardiac output. This report documents that continuous inhalation of low dose nitric oxide is capable of selective resolution of pulmonary hypertension following cardiac surgery for a large septal defect in a child. This suggests that a transient dysfunction in the release of nitric oxide by the pulmonary endothelial cell is responsible for the vasoconstriction. PMID- 8486874 TI - Hydrogen peroxide in expired breath condensate of patients with acute respiratory failure and with ARDS. AB - OBJECTIVE: Measurement of hydrogen peroxide concentrations in breath condensate of mechanically ventilated patients with ARDS and with risk factors for developing ARDS. DESIGN: Open study in intensive care patients. SETTING: Intensive care units of the Clinics of the University of Gottingen, a primary care center. PATIENTS: 10 post-operatively ventilated patients as a control group and 26 patients with acute respiratory failure, 7 of them with ARDS, 12 with polytrauma, 4 with pneumonia, 3 with cardiogenic or nephrogenic pulmonary edema. INTERVENTIONS: None. MEASUREMENTS: Breath condensate was collected by a special cold trap and was analysed for H2O2 by a chemiluminescence method. Daily measurements were performed for 4.2 +/- 2.6 days (mean +/- SD) as soon as possible after manifestation of respiratory failure. RESULTS: Patients with acute respiratory failure exhibited higher H2O2 concentrations than control patients (median 95 nmol/l, range 76-144 nmol/l), with the highest median value found in the ARDS group (552 nmol/l, range 154-893). After clinical improvement, H2O2 concentrations decreased to the range of the control group. CONCLUSION: Since high concentrations of H2O2 in breath condensate were only found in patients with ARDS or with risk factors for ARDS, the results add to the existing evidence that reactive oxygen species are associated with some acute lung diseases. PMID- 8486875 TI - Brain resuscitation by extracorporeal circulation after prolonged cardiac arrest in cats. AB - OBJECTIVE: Brain reanimation after prolonged ischemia is limited by post-ischemic reperfusion deficits (no-reflow phenomenon). The present study was undertaken to establish whether after 30 min cardiac arrest extracorporeal circulation is able to restore brain reperfusion and to promote functional and metabolic recovery. DESIGN: Adult normothermic cats were submitted to 30 min cardiac arrest by KCl induced cardioplegia. Resuscitation was carried out by extracorporeal circulation (ECC) until spontaneous heart function returned. The quality of brain recovery was assessed 3 h later by electrophysiological recording and by imaging of the regional distribution of brain energy metabolites. RESULTS: In 6 of 10 cats cardiac sinus rhythm returned after 32 +/- 15 min. In the other 4 cats cardiac function did not return or only intermittently returned during the 3 h observation period. Cerebral blood flow measured by laser Doppler flowmetry returned to 102% +/- 40% of control immediately after the beginning of resuscitation but then gradually declined to 43% +/- 32% after 3 h despite normotensive perfusion. In all cats pupils started to constrict within less than 5 min of recirculation but in 2 animals they secondarily dilated 1.5 and 2 h later, respectively. Spontaneous EEG activity reappeared in 4 of the 6 successfully resuscitated cats after 111 +/- 40 min but failed to recover in the others. Bioluminescent imaging of ATP after 3 h recirculation revealed near complete depletion throughout the brain in all 4 cats without cardiac recovery. Of the 6 successfully resuscitated cats 5 exhibited patchy areas of low ATP, glucose and pH in 22%-92% of the cross sectional area of brain; in one cat recovery of energy metabolism and acid-base homoeostasis was homogeneous without any focal deficits. The cross sectional area of ATP recovery correlated directly with CBF and hematocrit and inversely with the plasma lactate level. CONCLUSIONS: This study demonstrates for the first time that ECC is able to restore electrophysiological and metabolic brain function after cardiac arrest of as long as 30 min, but recovery is heavily restricted by delayed post-ischemic disturbances of recirculation. Progress in cardiac resuscitation by ECC requires substantial improvement in the efficiency of cerebrovascular reperfusion. PMID- 8486877 TI - Bronchial electrocardiography to determine left or right main bronchial placement of an endotracheal suction catheter tip. AB - OBJECTIVE: To assess the utility of a blue lined angle tipped and electrode tipped catheter, to guide left and right main bronchus cannulation. DESIGN: A prospective study. SETTING: An 11-bed general intensive care unit in a 900-bed teaching hospital. PATIENTS: 50 intubated intensive care patients, in sinus rhythm with normal P and QRS mean frontal axis, who required endobronchial suctioning for routine respiratory management. INTERVENTIONS: Endobronchial electrocardiography was used to position a blue lined angle tipped and electrode tipped suction catheter into the right and left main bronchi. RESULTS: Selective cannulation of the left main bronchi was determined by observing a biphasic or inverted P wave in 42 patients, or biphasic or inverted QRS complex in 31 patients. In 8 patients in whom no changes in the ECG were found, bronchoscopic placement of an ECG electrode into the left main bronchus demonstrated a biphasic or inverted P wave in 8 patients and a biphasic QRS complex in 3 patients, confirming the failure to cannulate the left main bronchus in these 8 patients. CONCLUSIONS: Using a blue lined, angle tipped and electrode tipped catheter for endotracheal suctioning, endobronchial electrocardiography may be a simple method to signal left or right main bronchus cannulation. PMID- 8486876 TI - Parenteral nutrition in the critically ill: use of a medium chain triglyceride emulsion. AB - OBJECTIVES: The study investigated the use of an intravenous lipid emulsion containing medium chain triglycerides (MCTs) in critically ill patients, and compared the effects with those of a conventional long chain triglyceride (LCT) preparation. DESIGN: Patients received a parenteral nutrition regime including either 500 ml 20% Lipofundin MCT/LCT (1/1) per day, or 500 ml 20% Lipofundin S (LCT) infused over 8 h each evening. SETTING: The patients were receiving treatment, including assisted ventilation, in the Intensive Care Unit of a large teaching hospital. All patients on this unit for at least 3 days and who were likely to receive parenteral nutrition for at least a week were considered, unless they had severe renal or liver disease, or trauma/major surgery in the previous 3 days. Because ICU patients are a heterogenous group, subjects were randomised within clinical groups to receive either lipid. There were 24 patients entered into the study and the data on 20 matched patients is reported. MEASUREMENTS AND RESULTS: Blood specimens were collected pre-TPN, daily at 0800 and after 5 h lipid infusion on days 1 and 6. Urine collections (24 h) were also performed. There were no apparent adverse effects due to the new MCT/LCT emulsion. Plasma ketone and glycerol concentrations were higher during MCT/LCT infusion, but 8 h post infusion plasma levels of ketones, triglycerides, non esterified fatty acids and glucose were similar. Urinary carnitine excretion was high in all patients and was not significantly different between the groups. Nitrogen balance was less negative in patients receiving MCT/LCT on days 6 and 9. CONCLUSION: MCTs are rapidly hydrolysed and oxidised to fatty acids and ketones which can be readily utilised. This study indicates that intravenous lipid emulsion containing MCT are safe in critically ill patients and may have advantages over LCT. The number and range of patients studied was, however, small and larger studies are needed. PMID- 8486878 TI - Are activity-based assessments of balance and gait in the elderly predictive of risk of falling and/or type of fall? AB - OBJECTIVE: To determine whether an activity-based test of balance and gait is predictive of the risk of: (1) falling in situations that are related to specific tasks evaluated as part of the test, (2) experiencing falls precipitated by different classes of biomechanical events, or (3) falling in general; and to compare the predictive ability of the activity-based test for the falls described in (2) and (3) to that of a posturography test that has been found previously to be predictive of falling risk. DESIGN: Cohort study. SETTING: Baseline tests performed in balance laboratory; subsequent history of falling monitored prospectively for 1 year in two residential-care facilities. PARTICIPANTS: Seventeen male and 83 female consecutive volunteers (mean age = 83, SD = 6) who were independent in activities of daily living and able to stand unaided. MEASUREMENTS: Independent variables were derived from an activity-based balance and-gait test and a posturography test. Dependent variables were the numbers of subjects with one or more: (1) falls in specific situations related to activity based test items, (2) falls related to general classes of biomechanical precipitant, and (3) falls in general. MAIN RESULTS: Subjects who were rated as "abnormal" in activity-based test items related to transfers, turning or reaching were more likely to experience one or more falls in related situations in everyday life. Activity-based scores were predictive of risk of experiencing falls with no obvious biomechanical precipitant and falls precipitated by center of-mass perturbation, but not falls precipitated by base-of-support perturbation. In comparison, a posturographic measure of spontaneous medial-lateral postural sway (blindfolded conditions) failed to predict falls having no biomechanical precipitant, but provided the best predictions of both center-of-mass and base-of support falls, as well as risk of falling in general. CONCLUSIONS: Activity-based testing of certain tasks (transfer, turning, reaching) may be useful in indicating a specific need for intervention to reduce the risk of falling during related everyday activities. In terms of predicting falling risk, a static posturography test may provide better prediction overall of the different classes of falls and may be useful as a quick and simple screening tool to help identify high-risk individuals. PMID- 8486879 TI - An audit of cardiac pacing in the elderly: effect of myocardial infarction on outcome. AB - OBJECTIVE: To audit the outcome of temporary endocardial pacing in an elderly population. DESIGN: Retrospective case-series analysis. SETTING: The Department of Medicine for the Elderly at the Wrexham Maelor Hospital, a District General Hospital with 612 beds serving a catchment population of 220,000. SUBJECTS: A sample of 50 consecutive elderly patients, with an age range of 65 to 99 years, undergoing transvenous cardiac pacing. MAIN OUTCOME MEASURES: Length of stay in hospital, complications of the pacing procedure, whether a permanent pacemaker was installed, and whether the patient died within 1 month of admission. RESULTS: There was no difference in length of stay between those with a myocardial infarction and those without. Minor complications occurred in three patients (one local infection and two "failures to pace"). Major complications occurred in two patients (septicemia and pneumonia). More patients without a myocardial infarction (86.9%) went on to implantation of a permanent pacemaker than those with an infarction (11.1%, P = 0.001), and fewer of them died (8.7% compared with 48.1%, P = 0.0025). In those patients with a myocardial infarction who died, there was no difference between the proportions who had inferior (7/18) and anterior (5/9) infarctions. CONCLUSION: Cardiac pacing seems to be a safe and reliable procedure in the elderly, although long term morbidity and mortality may be dependent on the presence or absence of myocardial ischaemic disease. Myocardial infarction in the elderly is an event of major significance, carrying with it a high mortality rate, particularly if accompanied by cardiogenic shock and the need for cardiac pacing. PMID- 8486880 TI - Correlates of cognitive function scores in elderly outpatients. AB - OBJECTIVE: To determine medical, ophthalmologic, and demographic predictors of cognitive function scores as measured by the Telephone Interview for Cognitive Status (TICS), an adaptation of the Folstein Mini-Mental Status Exam. A secondary objective was to perform an item-by-item analysis of the TICS scores to determine which items correlated most highly with the overall scores. DESIGN: Cross sectional cohort study. SETTING: The Glaucoma Consultation Service of the Massachusetts Eye and Ear Infirmary. SUBJECTS: 472 of 565 consecutive patients age 65 and older who were seen at the Glaucoma Consultation Service between November 1, 1987 and October 31, 1988. MEASUREMENTS: Each subject had a standard visual examination and review of medical history at entry, followed by a telephone interview that collected information on demographic characteristics, cognitive status, health status, accidents, falls, symptoms of depression, and alcohol intake. RESULTS: A multivariate linear regression model of correlates of TICS score found the strongest correlates to be education, age, occupation, and the presence of depressive symptoms. The only significant ocular condition that correlated with lower TICS score was the presence of surgical aphakia (model R2 = .46). Forty-six percent (216/472) of patients fell below the established definition of normal on the mental status scale. In a logistic regression analysis, the strongest correlates of an abnormal cognitive function score were age, diabetes, educational status, and occupational status. An item analysis using step-wise linear regression showed that 85 percent of the variance in the TICS score was explained by the ability to perform serial sevens and to repeat 10 items immediately after hearing them. Educational status correlated most highly with both of these items (Kendall Tau R = .43 and Kendall Tau R = .30, respectively). CONCLUSION: Education, occupation, depression, and age were the strongest correlates of the score on this new screening test for assessing cognitive status. These factors were stronger correlates of the TICS score than chronic medical conditions, visual loss, or medications. The Telephone Interview for Cognitive Status is a useful instrument, but it may overestimate the prevalence of dementia in studies with a high prevalence of persons with less than a high school education. PMID- 8486881 TI - Quinine sulfate for leg cramps: does it work? AB - OBJECTIVE: To study the efficacy of quinine in the prevention of nocturnal leg muscle cramps. DESIGN: Double-blind, randomized, crossover trial with four periods of observation, each lasting 2 weeks. SETTING: General internal medicine outpatient clinic. PARTICIPANTS: Ambulatory outpatients who experienced an estimated two or more typical nocturnal leg cramps per week. INTERVENTION: 200 mg of quinine taken at bedtime. MAIN OUTCOME MEASURES: Self-reported ratings of leg cramp frequency, duration, and intensity. RESULTS: Sixteen patients completed the trial. During the 2 weeks patients used quinine, there was no statistically significant reduction in mean leg cramp number (quinine 3.5 vs placebo 4.2, P = 0.48), mean leg cramp duration (quinine 152 seconds vs placebo 163 seconds, P = 0.89), or patient ratings of severity using a 1 (low) to 10 (high) scale (quinine = 4.2 vs placebo = 4.0, P = 0.83). CONCLUSION: No significant reduction in nocturnal leg cramp frequency, intensity, or duration could be found using nightly quinine in this study. Since quinine is not without the potential for side effects and drug interactions, clinicians need to carefully consider the likelihood of modest benefit associated with quinine against the potential for side effects and drug-drug interactions. PMID- 8486883 TI - Dementia, agitation, and care in the nursing home. AB - OBJECTIVE: To examine the behavioral and functional problems of the cognitively impaired. DESIGN: A survey of a cohort of residents from six nursing homes. PARTICIPANTS: Subjects were randomly selected based on a minimum age of 70 years and a Resource Utilization Group (RUG) classification of the Physical or Behavioral type. Of those eligible, 44% (n = 366) agreed to participate. The participants and non-participants had similar demographics except for a higher incidence of mental illness in the non-participant group, which did not have a significant impact on agitation. SETTING: Six nursing homes in New York City, three voluntary non-profit and three proprietary. MEASUREMENT: The study used chart review, assessment of residents' cognitive and functional abilities, nursing assistants' ratings of residents' functional abilities, behavioral problems, and the amount of effort required in care, and time-motion observations of staff-resident interactions. RESULTS: Residents' level of cognitive impairment had a significant impact on problem behaviors during ADL tasks, along with supervision required in patient care (P < 0.05). These results were validated by time-motion analysis. Regression analysis revealed that for non-demented subjects, the best indicator of care needs was health status, while for demented residents the best indicator was cognitive status (P < 0.0001). CONCLUSIONS: The care needs of residents with dementia are better estimated by a mental status test for cognitive impairment then by ADL assessment alone. Greater agitation is associated with increasing cognitive impairment. Further, agitation and behavioral problems associated with care result in a need for increased staff supervision. PMID- 8486882 TI - Hypouricemia, abnormal renal tubular urate transport, and plasma natriuretic factor(s) in patients with Alzheimer's disease. AB - OBJECTIVE: To study tubular urate transport in Alzheimer's disease (AD) and measure sodium and lithium transport rates in rats exposed to AD plasma. DESIGN: Cross-sectional study in three comparison groups. SETTING: Referral private institution involving outpatient and hospitalized patients. PATIENTS: AD, multi infarct dementia (MID) and non-demented controls (C) were selected and evaluated by a geriatrician and a psychiatrist according to availability and willingness to participate in the study. Demented patients had brain imaging, categorized according to NINCDS-DSM III criteria, and had Mini-mental status examination (MMSE) scores determined. INTERVENTIONS: Injection of 0.5 mL of plasma I.P. followed 120 minutes later by an IV plasma injection of 0.2 mL priming dose and infusion of 1.8 mL of plasma at 0.01 mL/min in Sprague Dawley rats. MEASUREMENTS: Renal clearance studies were performed in subjects and in rats exposed to the plasma of study subjects. We measured serum urate concentration and fractional excretion (FE) of urate in subjects and FE sodium and FE lithium in rats. RESULTS: Serum urate was lower and FE urate higher in 18 AD patients compared with six patients with MID, P < 0.05 and P < 0.005, and 11 C, P < 0.02 and P < 0.005, respectively. Higher FE sodium and FE lithium were noted in rats given plasma from 19 AD patients compared with 12 with MID, P < 0.005 and P < 0.0025, and 14 C, P < 0.0025 and P < 0.0005, respectively. FE sodium and FE lithium decreased progressively after serial dilutions of three AD plasmas and FE lithium was negatively correlated with MMSE scores only in AD, r = -0.71 and P < 0.0005. CONCLUSIONS: In AD there is defective tubular urate transport and a plasma natriuretic factor(s). FE sodium and/or FE lithium in rats exposed to plasma of demented patients may differentiate AD from MID and estimate the severity of AD. PMID- 8486884 TI - The effect of chlorothiazide on bone-related biochemical variables in normal post menopausal women. AB - OBJECTIVE: To evaluate the effects of short-term administration of chlorothiazide on fasting urinary hydroxyproline, an index of bone resorption, and other bone related biochemical parameters in normal post-menopausal women. DESIGN: Subjects served as their own control before and after chlorothiazide treatment. SETTING: Subjects were recruited by advertisement. PARTICIPANTS: Thirteen healthy post menopausal women with a mean age of 65 years. INTERVENTION: Each subject was given chlorothiazide 500 mg bd po for 7 days. Fasting blood and urine samples were obtained immediately before the commencement of chlorothiazide (day 1) and 2 and 7 days after starting chlorothiazide. RESULTS: Chlorothiazide decreased the urinary calcium/creatinine (mean value day 1, 0.267; day 2, 0.143; day 7, 0.135; P < 0.001) and hydroxyproline/creatinine (day 1, 0.0192; day 2, 0.0145; day 7, 0.0139; P < 0.02) molar ratios. CONCLUSION: Chlorothiazide decreases fasting urinary hydroxyproline, a marker of bone resorption in post-menopausal women. This observation supports a potential role for thiazide diuretics in the prevention of osteoporosis. The observed fall in urinary hydroxyproline is of the same order as that seen after treatment with estrogen or calcium supplements. PMID- 8486885 TI - Pain complaints and cognitive status among elderly institution residents. AB - OBJECTIVE: To examine the association between self-reported pain and cognitive impairment among frail elderly institution residents. DESIGN: A cross-sectional correlational study. SETTING: A large urban nursing home and congregate apartment complex housing predominantly Jewish elderly. PARTICIPANTS: Seven hundred fifty eight elderly institution residents (30% in the nursing home, 70% in congregate apartments). The sample was 70% female and averaged 83.3 years of age. MEASUREMENTS: Respondent self-reports tapped pain intensity, number of localized pain complaints, cognitive status, and disability in performance of activities of daily living. Attending physicians or physician assistants rated respondents' health status. MAIN RESULTS: Pain intensity and number of localized pain complaints bore small but significant negative relationships to cognitive impairment. Pain was positively associated with physician-rated ill health and functional disability. The association between pain and cognitive status remained significant even when controlled statistically for effects of physical health and functional disability. Item-by-item examination of localized pain complaints indicated that markedly cognitively impaired individuals were less likely to report pain in the back and joints. However, examination of possible physical causes of reported pain revealed no differences between pain reports of cognitively impaired versus intact individuals in either the presence or the absence of a likely physical cause. CONCLUSIONS: These data provide no evidence for the "masking" of pain complaints by cognitive impairment. They suggest instead that, although cognitively impaired elderly may slightly underreport experienced pain, their self-reports are generally no less valid that those of cognitively intact individuals. Limitations of the research are acknowledged and implications for treatment of cognitively impaired institution residents are discussed. PMID- 8486886 TI - The relationship between ankle-arm index and mortality in older men and women. AB - OBJECTIVE: To determine whether the ankle-arm blood pressure index is a useful predictor of mortality in a large group of patients aged 50 or older. DESIGN: Cohort study over a 13-year period. SETTING: Peripheral vascular laboratory in a hospital affiliated with an academic health center. PARTICIPANTS: 1,027 male and 903 female patients referred for arterial evaluation. OUTCOME MEASURES: All-cause and cause-specific mortality. RESULTS: A decrease in ankle-arm index was a strong independent predictor of all-cause mortality [relative risk (RR) for men = 1.8(95% CI 1.5, 1.9); for women = 1.5, (1.2, 2.0)] and atherosclerotic heart disease mortality [RR for men = 2.0 (1.4, 2.9); for women = 2.1 (1.4, 3.1)]. The risk of mortality was inversely proportional to the ankle-arm index. No relationship was found between the index and mortality due to stroke or cancer. CONCLUSIONS: These results suggest that a decreased ankle-arm index has important prognostic significance for mortality due to atherosclerotic heart disease in older men and women. Measurement of this index may be useful in identifying those at high risk who may benefit from aggressive therapeutic intervention. PMID- 8486887 TI - Acute exercise facilitates semantically cued memory in nursing home residents. AB - OBJECTIVE: To study the acute effects of non-strenuous physical exercise on memory retrieval and visuo-motor performance in old-old nursing home residents. DESIGN: A randomized control trial. SETTING: A nursing home. PARTICIPANTS: Ambulatory volunteers from the nursing home, with all 20 shown to be normal on mental status. Three were male and 17 female, with a means of 84.5 years for age and 9.3 years for education. They were divided at random into an exercise and a control group. INTERVENTION: A single 15-minute standardized bout of non strenuous exercise administered independently to each participant in the exercise group. Control group participants watched a video of similar exercises for 15 minutes. MEASUREMENTS: Two measures requiring the retrieval of category instances with semantic or initial consonant cues. Retrieval time was 60 seconds for each of four categories per measure. Visuo-motor performance was measured by Symbol Digit coding. Testing sessions were held before exercise, immediately post exercise and 30 minutes post-exercise. RESULTS: The group-by-time interaction was significant only for semantically cued memory (P < 0.01), with higher retrieval at post-testing only in the exercised group. The higher retrieval was mainly attributable to more new items retrieved by the exercise group at the immediate post-test (P < 0.05). CONCLUSIONS: This study provides preliminary support for the hypothesis that non-strenuous physical exercise has positive acute effects on meaningfully cued memory. PMID- 8486888 TI - Predicting short-term survival for patients with advanced Alzheimer's disease. AB - OBJECTIVE: The purpose of this study was to develop a statistical model for predicting short term survival in patients with dementia of the Alzheimer type (DAT). DESIGN: A prospective cohort study. SETTING: Three 25-bed intermediate medical care units using a structured approach to patient care management including palliative care options and patients from a second, traditional long term care setting. PARTICIPANTS: Of 104 patients with advanced DAT monitored for 34 months, 68 patients (97% white male) who had at least one fever episode were included in the model development phase. Data from 71 additional DAT patients with at least one fever episode were used to test the statistical model. MAIN OUTCOME MEASURES: Six-month survival following a fever episode. RESULTS: Older age and higher severity of DAT at the time of the fever episode, palliative care, and hospital admission for long-term care within 6 months prior to the fever were found to be positively associated with likelihood of mortality within 6 months of the fever onset. Adjusted odds ratios for each of these variables were statistically significant. The model performed well in subsequent testing on an independent sample of patients. CONCLUSION: Results provide a formula which can be used to predict likelihood of dying within 6 months following onset of a fever in DAT patients. This statistical prediction is recommended for use in combination with clinical judgment to certify DAT patients for Medicare hospice coverage. PMID- 8486889 TI - The problems of pain and its detection among geriatric nursing home residents. AB - OBJECTIVE: To assess physicians' detection of pain among geriatric nursing home residents and to determine if there are factors that may interfere with their ability to do this. DESIGN: Chart review and patient interview. SETTING: Geriatric nursing home. PARTICIPANTS: One hundred nursing home residents age 65 or older. Seventy-six were communicative. MEASUREMENTS: Demographic information, diagnoses, and medication use were compared for several groups of residents to determine their effects on the detection of pain. RESULTS: Sixty-six percent of the communicative residents were identified as having chronic pain. Treating physicians did not detect this problem in 34% of these residents. Those whose pain was not so identified were more likely to have a neurologic disorder other than dementia. When non-communicative residents were compared with those who were communicative, the physicians were found to have identified pain less frequently in the former cohort. CONCLUSIONS: Chronic pain is a common problem among geriatric nursing home residents and is frequently undetected. Identification of this problem among communicative residents may be markedly improved by direct questioning about this problem at frequent intervals. New methods of assessing pain need to be created to assist in its detection among the non-communicative population. PMID- 8486890 TI - Serum albumin and prealbumin as predictors of clinical outcomes of hospitalized elderly nursing home residents. AB - OBJECTIVE: To investigate the prevalence of hypoalbuminemia and hypoprealbuminemia in hospitalized, elderly, skilled nursing facility residents and to correlate these findings with clinical outcomes. DESIGN: Prospective cohort study. SETTING: A 300-bed community hospital. PARTICIPANTS: Eighty-one hospitalized, skilled nursing facility patients, average age 83.1 years. INTERVENTIONS: None. OUTCOME MEASURES: Serum albumin and prealbumin (transthyretin) were measured at admission, mid-week, 1 week, and 1 month. Patients were followed for 90 days for the outcomes of length of hospitalization and mortality. RESULTS: The prevalence of hypoalbuminemia was 99% and of hypoprealbuminemia, 79%. Both means dropped significantly from admission to midweek nadirs of 25 g/L for albumin and 14 mg/L for prealbumin. Severe hypoalbuminemia at mid-week predicted mortality (RR = 4.1 95%, CI 2.0-8.5) and extended length of hospitalization (RR = 5.2 95%, CI 2.8-9.8). Severe hypoprealbuminemia predicted extended hospitalization (RR = 3.2, CI 1.5-6.7) but not mortality. CONCLUSIONS: Hypoalbuminemia and hypoprealbuminemia are very common in this clinical setting and vary in parallel fashion over time. Severe hypoalbuminemia was a stronger predictor than hypoprealbuminemia of 90-day mortality and extended length of stay. Serum albumin on admission was not as strong a predictor of outcomes as serum albumin at mid-week. PMID- 8486891 TI - Dopamine B hydroxylase deficiency responsible for severe dysautonomic orthostatic hypotension in an elderly patient. AB - We report the case of an elderly woman with severe dysautonomic orthostatic hypotension in whom a deficit in dopamine B hydroxylase has been established. In the literature, such a deficit has been described in six young adults with long standing symptoms of postural hypotension. This enzyme catalyses the conversion of dopamine to noradrenaline. In our elderly patient, noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was detectable. Treatment with the synthetic amino acid, DL-threo-dihydroxyphenylserine, which is converted to noradrenaline by dopa-decarboxylase, resulted in a significant increase in blood pressure. The mechanism of this acquired deficit is not elucidated. PMID- 8486892 TI - The critical shortage of geriatrics faculty. AB - To estimate the adequacy of current and future supply of geriatrics faculty, we conducted a national survey to determine the current supply of geriatrics faculty in five specialties and compared these estimates to standards for optimal faculty supply in geriatrics. Finally, we generated a model to project future faculty supply based on both current training capacity and differing assumptions regarding future training capacity. Our findings indicate that the current supply of geriatrics physician faculty is less than half the number needed in each specialty. (Existing numbers range from a high of 909 faculty in internal medicine to a low of 86 in physical medicine.) Moreover, given the current capacity for training, there will be a net loss of such faculty each year in each specialty. We conclude that the number of geriatrics faculty currently available is insufficient to provide an appropriate "core" level of geriatrics training for all undergraduate medical students and residents in relevant residency programs. In addition, the current training capacity for geriatrics faculty cannot even sustain the current level of faculty over the next 10 years. To correct the current and future deficit, substantial increases in both geriatrics fellowship positions and mid-career training positions will be necessary. PMID- 8486893 TI - Mid-career faculty development awards in geriatrics: does retraining work? AB - OBJECTIVE: To evaluate the success of a mid-career physicians faculty retraining in geriatric medicine. DESIGN: Written survey of participants in the John Hartford Foundation's Mid-Career Faculty Development Program (1984-1988). SETTING: Four well established geriatric fellowship training programs. PARTICIPANTS: The 29 physicians who received John Hartford Foundation awards. RESULTS: Twenty-one (87%) of 24 respondents felt that the fellowship year had either a "major" or "significant" impact on their careers, and 87% also spend a significant portion of their time training others in geriatrics. CONCLUSION: This 4-year experiment in mid-career faculty retraining in geriatrics suggests that this approach is a viable alternative to traditional 2-year fellowships for helping to reduce the shortage of faculty in geriatric medicine. PMID- 8486894 TI - Psychoneuroimmunology and aging. PMID- 8486895 TI - The Medicare fee schedule in long-term care. PMID- 8486896 TI - Clock drawing as a screening tool. PMID- 8486897 TI - Geriatric fellowship training. PMID- 8486898 TI - Geriatric fellowship training. PMID- 8486899 TI - Geriatric fellowship training. PMID- 8486900 TI - Geriatric fellowship training. PMID- 8486901 TI - Geriatric fellowship training. PMID- 8486902 TI - Geriatric fellowship training. PMID- 8486903 TI - Geriatric fellowship training. PMID- 8486904 TI - VAE versus assisted suicide. PMID- 8486905 TI - VAE versus assisted suicide. PMID- 8486906 TI - Connecticut partnership for long-term care. PMID- 8486907 TI - Iatrogenesis: no advance directive. PMID- 8486908 TI - Cell proliferation in the respiratory tract of the rat after acute inhalation of formaldehyde or acrolein. AB - Male Sprague Dawley rats were exposed by inhalation for 6 h per day on one or three successive days to 0, 2, 6 or 20 ppm formaldehyde or 0, 0.2 or 0.6 ppm acrolein. Nasal and tracheal epithelial and free lung cells were then analyzed for proliferative responses. The proliferative response was expressed as the proportion of DNA synthesizing cells determined by the 5-bromodeoxyuridine (BrdU) labeling technique. Single exposure to both irritants increased the DNA synthesizing (proliferating) cells by a factor of 3. After three exposures the increase was distinctly lower. All sites analyzed showed approximately the same concentration/response pattern. Significant changes in cell proliferation could be detected at 2 ppm formaldehyde and 0.2 ppm acrolein. PMID- 8486909 TI - Oral toxicity in weanling and adult rats and in vitro genotoxicity of the veterinary anthelmintic rafoxanide. AB - The oral toxicity of the veterinary anthelmintic Rafoxanide was evaluated in newborn rats exposed in utero and during lactation. In another group, 3 months of oral treatment started after weaning. Rafoxanide administration to dams (10 mg kg 1) decreased the number of pups per litter, induced high mortality (42%) and delayed the growth of offsprings before weaning. Histopathological examination of the central nervous system revealed vacuolation of the white matter. Vacuolation was particularly severe in the cerebellum of the 14-21-day-old rats. Rafoxanide induced, in some pups (35%), the formation of cataracts. These toxic effects seemed to be reversible and were no longer detectable after a further 3-month administration of Rafoxanide (10 mg kg-1) to rats born of treated dams. In adult rats treated orally for 3 months with 1, 5 or 25 mg kg-1 Rafoxanide, biochemical and haematological tests did not reveal dose-related effects. Rafoxanide had no mutagenic activity in the Ames and CHO/HGPRT tests. PMID- 8486910 TI - Triethylbenzene-induced sensorimotor neuropathy in rats. AB - 1,2,4-Triethylbenzene (1,2,4-TEB) and 1,3,5-triethylbenzene (1,3,5-TEB) were administered orally to male Sprague-Dawley rats. Experimental and appropriate control rats were examined electrophysiologically for motor and sensory conduction velocities (MCV and SCV), and the amplitudes of the sensory (ASAP) and muscular action potentials (AMAP), at bi-weekly intervals. Oral administration of 1,2,4-TEB (200 or 400 mg kg-1, once daily, 4 days per week for 8 weeks) produced a time- and dose-dependent decrease in MCV, SCV, AMAP and ASAP. Rats treated with 1,2,4-TEB exhibited a bluish discoloration of the skin and the urine was greyish greenish. No changes in MCV, SCV, AMAP and ASAP developed in rats given 1,3,5-TEB orally (200 or 400 mg kg-1, daily, 4 days per week for 8 weeks). The results indicate that 1,2,4-TEB is a neurotoxic isomer of TEB and that the presence of two ethyl radicals in the ortho-position on an aromatic ring could be a critical molecular arrangement resulting in chromogenic and neurotoxic properties. PMID- 8486911 TI - Sensory and pulmonary irritation of aliphatic amines in mice: a structure activity relationship study. AB - The expiratory bradypnea indicative of upper airway irritation in mice was evaluated during a 15-min oronasal exposure to increasing concentrations of sixteen aliphatic amines. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each test compound. Moreover, the sixteen amines were tested for pulmonary irritation by measuring the decrease in respiratory rate of (non-anaesthetized) tracheally cannulated mice (RD50 TC). The RD50 and RD50 TC values and their ratios were related to n octanol/water partition coefficients (log P). The RD50 values associated with exposure to saturated amines ranged from 17 to 300 ppm. The RD50TC values for these saturated amines ranged from 35 to 489 ppm. The RD50 and RD50TC values of saturated amines were closely related to the n-octanol/water partition coefficient, indicating that the more lipophilic amines are more irritant for the upper and lower respiratory tracts. The RD50TC/RD50 values were much less closely related to the n-octanol/water partition coefficient. Based on the results, tentative standards are suggested for the studied amines. PMID- 8486912 TI - Induction of mast cell sensitization by chemical allergens: a comparative study. AB - In previous investigations we have shown that chemical allergens of different classes induce in mice qualitatively divergent immune responses. Respiratory allergens provoke substantial increases in total serum concentration of IgE. In contrast, contact allergens which are known or suspected not to cause respiratory sensitization or which at most have only a very limited potential to do so, have little or no effect on total serum IgE. Such differences, we propose, provide a novel approach for the prospective identification of chemicals with potential to cause respiratory allergy. In the absence of a robust method for the direct measurement of respiratory hypersensitivity reactions in mice we have sought in the present study to determine whether the IgE responses induced in mice by respiratory allergens are specific and of sufficient magnitude to cause the active sensitization of mast cells in vivo, a prerequisite for immediate hypersensitivity, including acute-onset respiratory hypersensitivity. Topical exposure of BALB/c mice to concentrations of > or = 10% of the human respiratory allergen trimellitic anhydride (TMA) caused the specific sensitization of peritoneal mast cells in situ as measured by the conjugate-induced release of [3H]-5-hydroxytryptamine in vitro. Experiments were performed also with 2,4 dinitrochlorobenzene (DNCB), a contact allergen that fails to induce respiratory hypersensitivity. Treatment of mice with concentrations of DNCB of comparable immunogenicity failed to cause mast cell sensitization. These data demonstrate that a known human chemical respiratory allergen induces in mice specific mast cell-sensitizing IgE antibody and reinforce the value of the mouse as a model for the evaluation of respiratory sensitization potential. PMID- 8486913 TI - Delayed neurotoxic effect of sarin in mice after repeated inhalation exposure. AB - Delayed neurotoxicity of sarin in mice after repeated inhalation exposure has been studied. Female mice exposed to atmospheric sarin (5 mg m-3 for 20 min) daily for 10 days developed muscular weakness of the limbs and slight ataxia on the 14th day after the start of the exposure. These changes were accompanied by significant inhibition of neurotoxic esterase (NTE) activity in the brain, spinal cord and platelets. Histopathology of the spinal cord of exposed animals showed focal axonal degeneration. These changes were comparatively less than in animals treated with the neurotoxic organophosphate, mipafox. Results from this study indicate that sarin may induce delayed neurotoxic effects in mice following repeated inhalation exposure. PMID- 8486914 TI - Dibromomethane and carbon monoxide in the rat: comparison of the cardiovascular and metabolic effects. AB - The goals of this study were to examine the cardiovascular and metabolic responses to a dihalogenated methane and to compare them to inhaled CO. One group of male Sprague-Dawley rats received an i.p. injection of either 3 or 6 mmol kg-1 dibromomethane (DBM) diluted 1:3 with sesame oil. Measurements of carboxyhemoglobin (COHb), rectal body temperature (BT), heart rate, systolic blood pressure (BP) and blood glucose and lactate concentrations were made at times 0, 30, 60, 120, 240, 360, 480, 600, 720, 840, 1020, 1440 and 1680 min. A second group of rats received only sesame oil and was tested in the same manner. A third group of rats breathed 225 ppm CO for 120 min before being tested. Peak COHb levels were 16% 8 h after 3 mmol kg-1 DBM, 18% 12 h after 6 mmol kg-1 DBM and 17% in the CO-exposed group. The sesame oil controls exhibited no elevation in COHb. The BT dropped by ca. 1 degree C in both the DBM- and CO-exposed rats, while there was no BT change in the sesame oil controls. The BT dropped by 1.0 degree C and 1.2 degree C after 6 h in the 3 and 6 mmol kg-1 DBM groups, respectively, and by 0.9 degree C after 120 min in the CO-exposed group. The CO exposed rats displayed a 12 mmHg decrease in systolic BP, while both doses of DBM failed to produce any significant BP change. The BP in the sesame oil controls remained constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8486915 TI - Body distribution and endocrine toxicity of hexachlorobenzene (HCB) in the female rat. AB - Hexachlorobenzene (HCB) residue levels in dosed rats (50.0 mg kg-1 body wt.day-1, n = 9) were significantly (P < 0.05) greater in the periovarian fat compared to the thyroid gland. Hexachlorobenzene residue levels were significantly (P < 0.05) greater in the thyroid versus the adrenal and ovary. Ovarian HCB residue levels were greater than those found in the thymus, liver and lung. Serum thyroxin (T4) and the free T4 index (FTI) were significantly (P < 0.05) suppressed in HCB treated rats compared to the control group (n = 8). In contrast, no significant differences in serum concentrations of oestradiol (E2), progesterone (P4) or percentage triiodothyronine uptake (%T3) were observed, thus suggesting an HCB induced hypothyroid-like state. In a second experiment, adult female Sprague Dawley rats (n = 16) were dosed as above and superovulated with pregnant mare serum gonadotrophin (PMSG, 10 IU s.c.) and human chorionic gonadotrophin (hCG, 20 IU s.c.). Circulating levels of P4 were significantly (P < 0.05) elevated compared to the control group (n = 8). The %T3 uptake and serum T4 levels were significantly (P = 0.05) suppressed compared to controls. Hexachlorobenzene treatment had no effect on circulating levels of E2 or on the FTI. These results suggest that HCB-induced changes found in the spontaneously cycling rat are augmented by ovulation induction strategies. We also conclude that HCB concentrates in the endocrine tissues in addition to the fat. PMID- 8486916 TI - Genetic toxicology studies with a tumor promoter. AB - A diuretic antihypertensive agent, SC-33643 (8-[2-ethoxyethyl]-7-phenyl [1,2,4]triazolo[4,3-c]pyrimidine-5- amine, also known as bemitradine), was tested in the Ames test, in the mouse lymphoma TK +/- mutation assay, in the Chinese hamster ovary cell hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) mutation test and in the CHO chromosome aberration assay with and without metabolic activation. Additionally, the compound was tested in the rat primary hepatocyte unscheduled DNA synthesis (UDS) assay and in the mouse bone marrow micronucleus assay. The results were uniformly negative. Contrary to expectations based on the results of the battery of genetic toxicology tests, the compound produced liver, thyroid and mammary tumors in the rat (reported separately). Subsequently, SC-36741 (5-amino-7-phenyl-[1,2,4]triazolo-[1,5-c] pyrimidine-8 ethanol, also known as desethylbemitradine), a major metabolite of SC-33643, was tested in the Ames test, in the CHO/HGPRT mutation test and in the CHO chromosome aberration assay with and without metabolic activation, and was also tested in the rat primary hepatocyte/UDS assay and in the mouse bone marrow micronucleus assay. This metabolite also produced negative results in these tests. Therefore, SC-33643 is a non-genotoxic carcinogen producing tumors in rats without altering DNA or chromosomes. PMID- 8486917 TI - Sailors' physicians: medical guides for merchant ships and whalers, 1774-1864. PMID- 8486918 TI - A Greek progymnasma on the physician-poisoner. PMID- 8486919 TI - When the doctors disagree: scientific temperance and scientific authority, 1891 1906. PMID- 8486920 TI - Western biology and medicine in modern China: the career and legacy of Alice M. Boring (1883-1955). PMID- 8486921 TI - Europium-labelled recombinant protein G. A fast and sensitive universal immunoreagent for time-resolved immunofluorometry. AB - Recombinant protein G was labelled with europium by conjugating the protein with Eu3+ chelate of a p-isothiocyanatobenzyl derivative of diethylenetriaminetetraacetic acid, a bifunctional chelating agent specifically optimized for labelling of immunoreagents with lanthanide ions. The labelling produced a universal reagent for time-resolved fluorometric immunoassays based on the principle of dissociative fluorescence enhancement (DELFIA). The optimum labelling level of about eight chelates per protein yielded a highly sensitive and stable reagent which retained its affinity for IgG and exhibited low non specific binding to coated solid surfaces. The reagent was evaluated in an immunoassay of anti-tetanus antibodies in human serum samples and the results were compared to those obtained with Eu-labelled polyclonal and Eu-labelled monoclonal anti-human IgG antibodies. The detection limit of the assay was 0.003 mU/ml (0.3 microU per assay well). After a 100-fold dilution of the samples, the assay range extended from 0.3 mU/ml to 100,000 mU/ml with a linear range of five log orders. The incubation with Eu-labelled protein G reached equilibrium after a 15 min incubation. The rapid kinetics, the low non-specific background and the high specific binding suggest that Eu-protein G can serve as a universal label for immunoassays based on IgG binding to solid surfaces. PMID- 8486922 TI - Antibodies to brain integral membrane proteins in systemic lupus erythematosus. AB - Wheat germ lectin affinity chromatography and temperature-induced phase separation with Triton X-114 were evaluated for the isolation of surface neuronal antigens from rat and human brain and from human neuroblastoma cell lines IMR-6 and SK-N-SH. Both techniques yielded surface proteins which were free of contamination by intracellular proteins but temperature-induced phase separation was technically less demanding and less expensive, required a shorter assay time and resulted in a superior quantity and quality of isolated proteins. Rat brain surface proteins were used for characterization of antineuronal antibody reactivity in sera from patients with systemic lupus erythematosus (SLE). Western blotting identified reactivity in 15 of 75 (20%) SLE sera compared to five of 95 (5%) normal controls (P 0.006). In rat brain the molecular weight of the individual proteins identified ranged from 59 kDa to 22 kDa. Six of these were also present in human brain and two were present in neuroblastoma cell lines. Absorption studies indicated that some of the antigenic proteins were either restricted to brain tissue or shared with other non-neuronal tissues. These techniques should facilitate the characterization of antineuronal antibody reactivities and lead to a clearer understanding of their role in the pathogenesis of autoimmune neurologic disease. PMID- 8486923 TI - A flow cytometric study of the membrane potential of natural killer and K562 cells during the cytotoxic process. AB - This study demonstrates that it is possible to investigate the membrane potential of interacting cells during the cytotoxic process using flow cytometry. Changes in the membrane potential of NK and K562 cells, involved in a cell-mediated cytotoxic process, were studied by standard and slit-scan flow cytometry, using the membrane potential sensitive fluorescent probe DiBAC4(3). The NK cells were labeled with a membrane marker (TR-18 or DiI) prior to incubation with K562 cells and the conjugates that were formed could be identified on the basis of the membrane marker fluorescence and light scattering signals. With a slit-scan technique we measured the membrane potential of each cell in a conjugate separately. The results show that depolarization of the K562 cell occurs as a consequence of the cytotoxic activity of the NK cell. This depolarization appears to be an early sign of cell damage because the cell membrane still remains impermeable to propidium iodide. Our data also indicate that depolarization of the NK cell occurs as a result of its cytotoxic activity. PMID- 8486924 TI - Preservation of phenotype and function of positively selected virus-specific CD8+ T lymphocytes following anti-Fab detachment from immunomagnetic beads. PMID- 8486925 TI - Modified procedure for labelling target cells in a europium release assay of natural killer cell activity. AB - Lanthanide europium chelated to diethylenetriaminopentaacetate (EuDTPA) can be used to label target cells such as tumor cells and lymphocytes (Blomberg et al., 1986a,b; Granberg et al., 1988). This procedure has permitted the development of new non-radioactive methods for the detection of target cell cytolysis by natural killer (NK) cells (Blomberg et al., 1986a,b), cytotoxic T lymphocytes (CTL) (Granberg et al., 1988) or complement-mediated cytolysis (Cui et al., 1992). However, we had no success with this method because of a lack of comparability between human NK cell activity simultaneously measured by a classical 51Cr release assay (Seaman et al., 1981) and EuDTPA release assay (Blomberg et al., 1986a). Furthermore, cell division and cell viability were significantly impaired by the suggested concentrations of EuCl3. In this paper, we present a modified non-cytotoxic method for target cell labelling with EuDTPA while cells are growing in culture medium. PMID- 8486926 TI - A quantitative ELISA for dystrophin. AB - A novel approach to the quantitation of the muscular dystrophy protein, dystrophin, in muscle extracts is described. The two-site ELISA uses two monoclonal antibodies against dystrophin epitopes which lie close together in the rod domain of the dystrophin molecule in order to minimize the effects of dystrophin degradation. Dystrophin is assayed in its native form by extracting with non-ionic detergents and avoiding the use of SDS. PMID- 8486927 TI - Simultaneous electroelution of whole SDS-polyacrylamide gels for the direct cellular analysis of complex protein mixtures. AB - A novel procedure which allow the rapid screening of complex protein mixtures in cellular assays is described. A device has been developed which allows a convenient, simultaneous electroelution of separated proteins from whole SDS polyacrylamide gels into narrow chambers each containing single or a few protein bands. We have optimized the conditions of the procedure and have obtained an efficient removal of SDS, leading to non-toxic protein fractions in a physiological buffer suited for direct testing in cell cultures. The responses generated by stimulating lymphocytes with the purified products have been compared to the native protein and a corresponding preparation of protein transferred to nitrocellulose particles. The method was used to investigate murine T cell responses to secreted mycobacterial antigens during infection with M. tuberculosis. A immunodominant secreted protein fraction was purified in a semipreparative scale by the procedure and used to immunize mice. The specificity of and lymphokine production by T cells generated in these animals were investigated. The device developed has various applications and provides a tool for the possible identification of new T cell antigens of importance for protective immunity. PMID- 8486928 TI - Detection of distinct sets of newly synthesized polypeptides in supernatants of TCR-triggered T cell clones. Implication for the search for new lymphokines. AB - Using metabolic radiolabelling of proteins, which are newly synthesized during TCR-triggered T cell activation we were able to visualize distinct patterns of secreted polypeptides (with molecular weights ranging from 6 to 44 kDa) in supernatants of different T helper-1, T helper-2 and cytotoxic T cell clones. Most of these detected proteins are secreted in response to TCR-crosslinking (or to combined action of PMA and A231287), in an extracellular Ca(2+)-dependent manner and their appearance in supernatants was completely blocked by the addition of RNA synthesis or protein synthesis inhibitors or EGTA. Cyclosporin A (CsA) blocks secretion of several detected polypeptides, but does not affect TCR triggered synthesis and secretion of others reflecting the existence of TCR triggered, CsA-insensitive protein synthesis and secretion pathway. The insensitivity of secretion of several easily detectable polypeptides to inhibition by CsA offers a promising approach to further define the CsA-resistant and calcineurin-independent molecular pathways of TCR-triggered T cell activation. Several lymphokines (e.g., interferon-gamma, tumor necrosis factor, interleukin-4 and interleukin-10) are identified among the visualized set of secreted polypeptides. Since other, yet unidentified, secreted polypeptides in the same set of secreted proteins share important properties with known lymphokines it seems promising to use described approach in search for new lymphokines. PMID- 8486929 TI - Quantitation of IL-4 expression in small numbers of cells from mice. AB - Interleukin-4 (IL-4) is an important T cell and mast cell product that participates in allergic and cytotoxic responses, as well as functions as a growth factor for B, T, and inflammatory cells. Studies of the expression of IL-4 by T cells present in inflammatory reactions would be facilitated by using polymerase chain reaction (PCR) coupled to reverse transcription of mRNA to amplify the small quantity of mRNA present in these cells. In order to use this method in a quantitative manner, a plasmid was constructed that contained a modified form of mouse IL-4 cDNA. This plasmid was transcribed to produce cRNA for this modified sequence. The cRNA was used as an internal standard for the reverse transcription and amplification of IL-4 transcripts in RNA samples from mouse thymocytes. Amplification of reverse-transcribed native IL-4 mRNA produced a 286 bp PCR product. Amplification of the reverse-transcribed standard RNA produced a 155 bp product, which reflected a deletion introduced into the original IL-4 cDNA sequence. Comparison of the amount of the 286 bp native product to the amount of 155 bp standard product enabled the quantitative determination of IL-4 expression in each sample. This method was used to demonstrate that platelet activating factor increases the expression of IL-4 in mouse thymocytes and in a mouse T cell line. The expression of IL-4 by thymocytes exposed to platelet-activating factor (PAF) may reveal an important link between inflammation and the maturation of T cells in the thymus. PMID- 8486930 TI - Detection of human T cell receptor cDNAs (alpha, beta, gamma and delta) by ligation of a universal adaptor to variable region. AB - The study of T cell receptor (TCR) genes has been hampered by their large repertoires and elusive methods for gene amplification. We have developed a new method for amplification of all human TCR genes (alpha, beta, gamma, and delta) with the ligation of a universal adaptor to the leader sequence of variable (V) regions, which permitted effective and reproducible amplification of all four types of TCR genes. cDNA sequencing of TCR-gamma, -delta, -alpha, -beta was carried out in respectively 15, 13, 28, and 26 T cell clones from human peripheral blood T cells using a newly developed universal adaptor and these methods. TCR-gamma V-II (V gamma 9) was a major population, and V-I (V gamma 2 and 3) and V-III (V gamma 10) were next major populations among TCR-gamma subfamilies, and confirmed the previous observations determined using mAbs specific to TCR-gamma. All five clones of TCR-gamma V-II and three of five clones of TCR-gamma V-I subfamilies had in-frame V-N-J junctions. In contrast, sequences from both TCR-gamma V-III (4/4 clones) and V-IV (1/1 clones) subfamilies had intron-like regions that caused out-of-frame cDNA, suggesting that most of TCR gamma V-III and V-IV in PBL are not functional. V delta 2 was a major population and V delta 1 was a next predominant population among TCR-delta subfamilies, also confirming the previous observations determined using mAbs to TCR-delta. With regards to TCR-alpha and -beta, this new method randomly amplified TCR cDNAs. In addition, the sequences of 5' portions of three TCR-V-alpha and one TCR-V beta were extended. Two new TCR-alpha subfamilies and one new TCR-beta family were also identified. In summary, this new method will provide a scientific tool for understanding structures of the human TCR genes involved in specific immune responses. PMID- 8486931 TI - Characterization of human tumor cell lines transduced with the cDNA encoding either tumor necrosis factor alpha (TNF-a) or interleukin-2 (IL-2). AB - Tumor cell lines were generated from cancer patients, 17 with metastatic melanoma and one with colon adenocarcinoma. The lines were characterized as tumor cells by the presence of tumor associated antigens demonstrated by indirect immunofluorescence and analysing using a fluorescence activated cell sorter (FACS). The tumor cell lines were transduced using retroviruses encoding neomycin phosphotransferase and either human tumor necrosis factor alpha (TNF-alpha) or interleukin-2 (IL-2). Following transduction, cells were selected and grown in the neomycin analogue G418. Fibroblasts overgrew tumor cells in 6/18 cases following selection in G418 and 1/18 lines did not grow at all after selection. In the remaining 11 lines the expression of tumor associated antigens, growth, and susceptibility to lysis by LAK cells was similar between the selected transduced tumor cell lines and the nontransduced controls. Of the lines tested, all were positive for the presence of the cytokine gene by Southern blot or PCR analysis. In addition, no replication competent retrovirus was detected in the cell lines following transduction using an extended mink S+L- focus assay. The amount of specific cytokine produced per 10(5) transduced tumor cells in 24 h ranged from 0.2 ng to 5.8 ng of TNF-alpha for the TNF transduced lines and from 0.1 ng to 3.6 ng of IL-2 for the IL-2 transduced tumor cell lines. One transduced tumor cell line examined maintained consistent levels of cytokine production when studied at 15 different time intervals over a period of 198 days. Additionally, 40,000 rads of gamma irradiation did not stop cytokine production from two transduced tumor cell lines when studied over 6 days. This study demonstrates the feasibility of growing human tumor cell lines from surgical biopsies and genetically modifying those lines to produce a cytokine of choice for possible use as a tumor cell vaccine. PMID- 8486932 TI - Monoclonal antibody-specific immobilisation of erythrocyte antigens (MAIEA). A new technique to selectively determine antigenic sites on red cell membranes. AB - A new assay, the monoclonal antibody-immobilization of erythrocyte antigens (MAIEA) is described for the assignment of red cell antigens recognised by human allo-antisera, to particular membrane components of the red cell membrane. This technique detects tri-molecular complexes formed by the reaction of a human antibody and a mouse antibody with a particular red cell protein. A positive reaction, in an ELISA-type detection procedure, occurs if the epitopes recognised by the human and mouse antibodies are present on the same membrane component but different regions. The MAIEA assay has been developed to investigate blood group antigens and in this report its application to the study of the Lutheran, Yt and Kell blood group systems is described. The technique has been used to show that the Lu(a) and Lu3 antigens are carried on the Lutheran glycoprotein, Yta and Ytb on the enzyme acetylcholinesterase and K, k, Kpa and Kpb on the Kell glycoprotein. PMID- 8486933 TI - Optimization of a time-resolved immunofluorometric assay for tumor-associated trypsin inhibitor (TATI) using the streptavidin-biotin system. AB - We have developed two 'sandwich'-type time-resolved immunofluorometric assays (IFMA) for tumor-associated trypsin inhibitor (TATI) using monoclonal and polyclonal antibodies. In the standard assay the monoclonal antibody was immobilized onto the walls of polystyrene microstrip wells and the polyclonal reagent was labeled with a europium chelate. We tested various assay conditions in order to optimize the assay for sensitivity and measuring range. Purification of the labeled antibody by hydrophobic interaction chromatography was found to be the most important single factor affecting sensitivity. Assay sensitivity and range were also improved by acid treatment of the solid phase antibody. To improve the sensitivity further the streptavidin/biotin (SAB) system was incorporated into the IFMA technique. In this simple and fast streptavidin/biotin IFMA (SAB-IFMA) we used streptavidin-coated wells to which we added biotinylated monoclonal antibody and a serum or urine sample. After incubation for 1.5 h and washing, the polyclonal europium-labeled tracer antibody was added. After incubation for 1 h the wells were washed and the Eu fluorescence measured. The assay performance of the SAB-IFMA was compared to the standard IFMA and radioimmunoassay (RIA). The detection limit was 0.05 microgram/l and the analytical range 3000-fold. The mean analytical recovery was 101%. Other advantages of the SAB-IFMA were high sensitivity and the low amounts of monoclonal antibody required, only 1/50 of that used in the standard IFMA. PMID- 8486934 TI - Vitamin A, infectious disease, and childhood mortality: a 2 solution? AB - Vitamin A was first discovered in 1913. Its deficiency was soon associated in animal models and case reports with stunting, infection, and ocular changes (xerophthalmia) resulting in blindness. The ocular consequences dominated clinical interest through the early 1980s. A longitudinal prospective study of risk factors contributing to vitamin A deficiency and xerophthalmia revealed a close, dose-response relationship between the severity of mild preexisting vitamin A deficiency and the subsequent incidence of respiratory and diarrheal infection (relative risk [RR], 2.0-3.0) and, most dramatically, death (RR, 3.0 10.0). Subsequent community-based prophylaxis trials of varying design confirmed that vitamin A supplementation of deficient populations could reduce childhood (1 5 years old) mortality by an average of 35%. Concurrent hospital-based treatment trials with vitamin A in children with measles revealed a consistent reduction in measles-associated mortality in Africa of at least 50%. It is now estimated that improving the vitamin A status of all deficient children worldwide would prevent 1-3 million childhood deaths annually. PMID- 8486935 TI - Early viremia and immune responses in vertical human immunodeficiency virus type 1 infection. AB - Thirty-three infants born to human immunodeficiency virus type 1 (HIV-1) seropositive women were evaluated from birth using plasma and peripheral blood mononuclear cell (PBMC) cultures, polymerase chain reaction, and serum p24 antigen assays. Five children were identified as infected. Evidence of infection was found in cord blood and subsequent samples from 2 infected children, suggesting in utero infection. Virologic studies on cord blood and early neonatal specimens from the 3 other infected children were negative but became positive by 8 weeks of age, suggesting either intrapartum transmission or sequestration of virus with subsequent detection. An increase in blood (plasma and PBMC) virus titers consistent with primary viremia was observed in 4 infants between 3 and 16 weeks of age. Blood virus titers subsequently declined in the absence of antiretroviral therapy and in the absence of activated HIV-1-specific cytotoxic T lymphocyte responses or broadly neutralizing antibodies. Confirmation of these results in larger studies may be helpful in the design of clinical trials to interrupt vertical transmission or to modify the course of infection. PMID- 8486936 TI - Identification of a type-specific protein that differentiates serologically between human T cell lymphotropic virus types I and II. AB - The 24-kDa band formed when sera of humans infected with human T cell lymphotropic virus type I (HTLV-1) were reacted with HTLV-I lysates in conventional Western blot (WB) assays was found to be composed of two immunologically unrelated proteins of 24- and 23-kDa. p24, but not p23, carries epitopes shared by the major core proteins of the other known transactivating C type retroviruses. p23 is unrelated immunologically to the env and tax HTLV-I products but partly cross-reacts with HTLV-I p19. All HTLV-I and simian T cell leukemia virus type I sera tested reacted with p23. Reactivity with p23 was seen with some HTLV-I sera that did not react or reacted weakly with HTLV-I p24. No reactivity with p23 was seen among the 51 human HTLV-II sera tested nor among a large panel of control sera. Because of its type-specificity and strong immunogenicity, p23 provides a reliable serologic marker for the diagnosis of HTLV-I infection and for distinguishing between HTLV-I and -II. PMID- 8486937 TI - Candidate recombinant vaccine for human B19 parvovirus. AB - Recombinant baculoviruses were used to produce human B19 parvovirus empty capsids composed of only VP2 and VP2 capsids containing 4%, 25%, 35%, or 41% VP1 protein. Immunogenicity of the purified capsids, formulated with or without adjuvant, was evaluated in mice, guinea pigs, and rabbits. Sera were analyzed for total anti B19 parvovirus antibodies, antibodies specific to the region unique to the VP1 capsid protein, and virus neutralizing antibodies. A relationship was observed between the development of antibodies specific to sequences unique to the VP1 protein and virus neutralization. The polypeptide composition of the empty capsid immunogens appeared to be important for elicitation of potent virus neutralizing activity. VP2 capsid immunogens devoid of VP1 protein, or consisting of only 4% VP1, the composition of naturally occurring virions, were generally poor at eliciting high levels of virus neutralizing activity. Capsids consisting of > or = 25% VP1 protein efficiently and consistently provoked vigorous B19 virus neutralizing responses. Recombinant empty capsids enriched for the VP1 protein should serve as the basis for a human B19 parvovirus vaccine. PMID- 8486938 TI - The 5C protein of Neisseria meningitidis is highly immunogenic in humans and induces bactericidal antibodies. AB - The 5C protein is expressed by the strain of Neisseria meningitidis (44/76) used for production of the Norwegian meningococcal group B outer membrane vesicle vaccine and is included in the final formulation of this vaccine. The immunoglobulin G antibody response to 5C stimulated by vaccination, systemic meningococcal disease, and carriage was measured using ELISAs with synthetic liposomes as antigen and by immunoblotting. Increased levels of IgG were found in paired sera from all three groups. The antibodies were bactericidal to meningococci of serogroups A and B that expressed large amounts of 5C but not to meningococci expressing smaller amounts. There was a linear correlation between bactericidal titer and units of IgG to 5C. PMID- 8486939 TI - Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. AB - The ability of Borrelia burgdorferi to attach to and invade human fibroblasts was investigated by scanning electron and confocal microscopy. By scanning electron microscopy, B. burgdorferi were tightly adherent to fibroblast monolayers after 24-48 h but were eliminated from the cell surface by treatment with ceftriaxone (1 microgram/mL) for 5 days. Despite the absence of visible spirochetes on the cell surface after antibiotic treatment, viable B. burgdorferi were isolated from lysates of the fibroblast monolayers. B. burgdorferi were observed in the perinuclear region within human fibroblasts by laser scanning confocal microscopy. Intracellular spirochetes specifically labeled with monoclonal anti flagellin antibody were also identified by fluorescent laser scanning confocal microscopy. These observations suggest that B. burgdorferi can adhere to, penetrate, and invade human fibroblasts in organisms that remain viable. PMID- 8486940 TI - Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. AB - Groups of 25-30 nymphal Ixodes dammini infected with Borrelia burgdorferi fed on mice for 36, 42, or 48 h. Only 1 (7%) of 14 mice exposed for 36 h became infected as did 3 (25%) of 12 mice exposed for 42 h and 6 (75%) of 8 mice exposed for 48 h. The minimum transmission rate calculation for ticks attached for 36 h was 0.5%; for 42 h, 1.5%; and for 48 h, 5.8%. Homogenates derived from nonfed "flat" nymphs or nymphs fed for 12 h were not infectious to mice. Homogenates derived from nymphs attached for 24 h, however, infected 20% of inoculated mice; homogenates derived from ticks attached for > or = 36 h infected > or = 80% of inoculated mice. Incubation of nonfed ticks at 37 degrees C did not produce infectious homogenates. The ID50 for low-passage JD1 strain spirochetes in 3-week old mice was 2.69 x 10(3) spirochetes. PMID- 8486941 TI - Induction of interleukin-1 release by high- and low-passage isolates of Borrelia burgdorferi. AB - Low-passage isolates of Borrelia burgdorferi induced arthritis when injected into the hind paws of irradiated hamsters, while high-passage isolates did not. To examine a possible mechanism for induction of arthritis, peritoneal exudate cells were coincubated with high- and low-passage isolates of B. burgdorferi, and the resultant conditioned medium was assayed for interleukin-1 (IL-1) activity. Comparable amounts of IL-1 activity were detected in culture supernatants generated by high- and low-passage spirochetes and were dependent on the number of spirochetes added. Live B. burgdorferi stimulated greater release of IL-1 activity than did heat-killed organisms. No evidence of release of IL-1 due to shedding of soluble components from spirochetes was obtained. A recombinant human IL-1 receptor antagonist blocked the proliferative activity of conditioned medium in a murine thymocyte assay for IL-1 activity. The greater ability of low-passage spirochetes to survive in vivo may be more important than the ability to induce IL-1 production in the pathogenesis of Lyme arthritis. PMID- 8486942 TI - Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. AB - Neonates born to women with reactive serologic tests for syphilis were studied; the total of 116 included 18 who were symptomatic, 60 asymptomatic but possibly infected, and 38 asymptomatic and probably uninfected. The fluorescent treponemal antibody-absorption (FTA-ABS) 19S IgM test and an IgM capture ELISA for Treponema pallidum, both treponema-specific assays, and the reverse enzyme-linked immunospot (RELISPOT), which detects immunoglobulin-secreting cells and is a nonspecific indicator of infection, were evaluated. Sensitivities among symptomatic neonates were 88% (IgM ELISA), 73% (FTA-ABS), and 78% (RELISPOT). Specificities ranged from 97% to 100%. A major problem has been the inability to identify which asymptomatic but possibly infected neonate is really uninfected. Among 41 such babies who had all three tests done, 93% were negative by all assays, suggesting they were uninfected or recently infected. Strategies to accurately identify the truly uninfected asymptomatic newborn would prevent the unnecessary hospitalization of all at-risk infants, resulting in improved quality of care and reduced costs. PMID- 8486943 TI - VDRL antibodies enhance phagocytosis of Treponema pallidum by macrophages. AB - Although reactivity in nontreponemal tests develops in patients with untreated syphilis, no immunologic function has been ascribed to these antibodies. This study demonstrates that rabbit antibodies induced by immunization with VDRL antigen and VDRL antibodies affinity-purified from syphilitic rabbit serum enhance phagocytosis of Treponema pallidum. The proportion of macrophages ingesting treponemes in the presence of these antisera was 45% +/- 5% and 27% +/- 4%, respectively, versus 14% +/- 3% for normal serum (P < .001 and P < .01). Both IgG and IgM fractions contained opsonic activity. Absorption of VDRL antibodies from syphilitic serum diminished but did not eliminate opsonization, suggesting at least two classes of target molecules. Despite opsonic capacity, VDRL antibodies fail to facilitate macrophage-mediated killing of T. pallidum. Nevertheless, VDRL-immunized rabbits are partially protected against T. pallidum infection, developing fewer lesions (delayed and smaller) than do unimmunized controls. These results suggest a heretofore unrecognized functional role for VDRL antibodies in syphilis infection. PMID- 8486944 TI - Prevention of group B streptococcal colonization and bacteremia in neonatal mice with topical vaginal inhibitors. AB - Pregnant Swiss-Webster mice were vaginally inoculated with 10(5) virulent and avirulent serotype III Streptococcus agalactiae and treated 4 days later with topical vaginal inhibitor solutions. Preparations containing lipoteichoic acid (LTA) or glycerophosphate (GP), the repeating linear backbone of LTA, significantly reduced neonatal colonization and bacteremia by the virulent isolate and colonization by the avirulent strain. Similar results were obtained if bacteria were preincubated with LTA or GP at 37 degrees C for 30 min before vaginal inoculation. Human serum albumin (HSA), a known inhibitor of binding of LTA to human fetal epithelial cells, also resulted in reduction in colonization and bacteremia of neonatal mice. However, maternal treatment with a combination of HSA (2%) and GP (1%) completely prevented neonatal colonization and bacteremia without altering the normal aerobic bacterial vaginal flora. These results provide impetus to the development of an alternative means of preventing neonatal group B streptococcal infections in humans without requiring maternal immunization or chemoprophylaxis. PMID- 8486945 TI - Inhibition of platelet binding and aggregation by streptococcal exopolysaccharide. AB - Streptococcal exopolysaccharides are major virulence factors in the pathogenesis of endocarditis. They promote bacterial adherence to valves and subsequent vegetation formation. Since platelet binding and aggregation by streptococci are postulated mechanisms for endocardial colonization and vegetation production, the effect of exopolysaccharide on binding and aggregation was evaluated by flow cytometry and aggregometry. Streptococcus salivarius D1, a minimal exopolysaccharide producer, bound human platelets extensively (86.8% of bacteria bound by 1 min). S. Salivarius M13 and M15 and Streptococcus mitis M4 produced larger amounts of exopolysaccharide and bound platelets significantly less (52.6%, 51.2%, 52.8%, respectively). Exopolysaccharide also inhibited platelet aggregation: Strains with minimal exopolysaccharide aggregated platelets maximally, while strains with extensive exopolysaccharide failed to induce aggregation. Removal of exopolysaccharide by shearing restored aggregation by these latter strains. Thus, exopolysaccharides can inhibit the binding and aggregation of platelets by streptococci. The virulence associated with exopolysaccharide may result from the inhibition of platelet-mediated interactions that limit disease progression. PMID- 8486946 TI - Legionella pneumophila replicates within rat alveolar epithelial cells. AB - Legionella pneumophila replicates in the distal pulmonary airspace, causing legionnaires' pneumonia. Legionella organisms replicate within alveolar macrophages and recruited blood monocytes; however, when these cells are activated, they become potent inhibitors of L. pneumophila proliferation. L. pneumophila may replicate in other cells and thereby avoid the host defenses of macrophages. Experiments demonstrated that L. pneumophila replicate within primary cultures of rat pulmonary alveolar epithelial cells. Double-label immunofluorescent and electron microscopy demonstrated L. pneumophila within epithelial cells. Replication of L. pneumophila required similar numbers of alveolar epithelial cells or alveolar macrophages, required viable epithelial cells, and took place intracellularly. While replication of L. pneumophila occurred in both serum-free and serum-containing media, it was enhanced in the presence of serum. Pulmonary alveolar epithelial cells may represent an alternative site for replication of Legionella species in the terminal airspace and thus clarify some previously unexplained aspects of the pathogenesis of legionnaires' disease. PMID- 8486947 TI - Attachment and entry of Legionella pneumophila in Hartmannella vermiformis. AB - Legionella pneumophila is an intracellular parasite of Hartmannella vermiformis. Attachment to the amebae and entry of L. pneumophila were studied by two quantitative assays: One used plate counts to measure the number of bacteria attaching to amebae at 4 degrees C; the other determined the number of intracellular bacteria by use of transmission electron microscopy (TEM). The attachment assay showed that L. pneumophila are inefficient in attachment to amebae. About 0.05% of the bacteria were bound after 1 h with a 10- to 40-fold increase over the next 11 h. Attachment of both virulent and avirulent strains of L. pneumophila occurred at a similar rate. Uptake of L. pneumophila was measured by counting intracellular bacteria using TEM. Limited numbers of virulent L. pneumophila were found intracellularly before 4 h, but the numbers increased logarithmically after this time. The number of amebae containing virulent L. pneumophila increased linearly during the 12-h co-incubation. Avirulent L. pneumophila were rarely detected within amebae throughout the 12-h incubation. Results indicate that entry, not attachment, of virulent L. pneumophila is the limiting step in infection of axenically grown H. vermiformis. PMID- 8486948 TI - Inhibition of lipid A- and lipopolysaccharide-induced cytokine secretion, B cell mitogenesis, and lethal shock by lipid A-specific murine monoclonal antibodies. AB - Three murine hybridomas secreting IgM monoclonal antibodies (MAbs) to lipid A (LA) of Salmonella minnesota R595 were generated. These MAbs serologically cross reacted with LA and lipopolysaccharide (LPS) of unrelated gram-negative bacterial species. All three MAbs significantly suppressed the ability of LA and LPS from various gram-negative bacteria to induce tumor necrosis factor (TNF)-alpha (36% 67%) and interleukin-1 (30%-98%) in murine peritoneal macrophages and to stimulate B lymphocytes (37%-78%). Lipid A-induced TNF alpha production was also suppressed in mice (86%-88%). All three antibodies protected adrenalectomized mice against lethal shock induced by LA of S. minnesota R595. Optimal protection was achieved with one of the antibodies (MLA-1), if it was administered 2 h before injection of lipid A, and full protection persisted < or = 24 h. Moreover, MLA-1 was able to protect adrenalized or D(+)-galactosamine-sensitized mice against lethal shock induced by LPS derived from various gram-negative bacteria. This cross-protection could be predicted on the basis of serologic cross reactivity and cross-neutralization by MLA-1 of the bioactivity of the heterologous LA or LPS in vitro. PMID- 8486949 TI - The major secreted antigen complex (Ag 85) from Mycobacterium bovis bacille Calmette-Guerin is associated with protective T cells in leprosy: a follow-up study of 45 household contacts. AB - T cell proliferation and interferon (IFN)-gamma secretion were analyzed in 45 leprosy contacts stimulated with antigen 85 (Ag85), the major culture filtrate antigen from Mycobacterium bovis bacille Calmette-Guerin. All 14 Mitsuda reaction positive contacts reacted to Mycobacterium leprae and Ag85. Three Mitsuda reaction-negative contacts reacted weakly to M. leprae and Ag85. The other 28 Mitsuda reaction-negative contacts did not react to M. leprae, but 9 reacted to Ag85. Thirty-four contacts were retested 16 months later. Eleven contacts initially positive by the Mitsuda test remained lepromin positive and reactive to M. leprae and Ag85. Fourteen contacts initially negative by the Mitsuda test converted, and all reacted in vitro to M. leprae and Ag85. Finally, 9 contacts remained Mitsuda test-negative, and 7 were unreactive to Ag85. In vitro reactivity to Ag85 at baseline in Mitsuda test-negative contacts was associated with subsequent conversion to lepromin reactivity in 7 of 9 subjects. These data suggest that reactive T cells against Ag85 develop very early during M. leprae infection and that Ag85 is a potentially protective T cell immunogen. PMID- 8486950 TI - Induction of tumor necrosis factor-alpha in murine Candida albicans infection. AB - Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis. Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator in the endotoxic shock syndrome. The possible role of TNF alpha causing early deaths was explored in a murine model of acute infection with Candida albicans. In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained. Peritoneal macrophages from all three strains produced TNF alpha in vitro when stimulated with C. albicans. After intravenous infection with 10(8) cfu of C. albicans, mice died within 12 h. TNF concentrations in sera from these mice were significantly greater than in controls. Pretreatment of BALB/c mice with anti-murine TNF alpha did not alter mortality of C. albicans-infected mice, but pretreatment with murine TNF alpha reduced mortality. Therefore, in contrast to what was anticipated, TNF alpha may serve a protective role in murine candidiasis. PMID- 8486951 TI - Response to treatment for an intracellular infection in a T cell-deficient host: toxoplasmosis in nude mice. AB - To examine the experimental basis of treatment failures in T cell-deficient patients with intracellular infections, euthymic and athymic (nude) BALB/c mice were infected with Toxoplasma gondii and treated with sulfadiazine. All euthymic and nude mice survived during 2 weeks of sulfadiazine therapy. Once treatment was discontinued, 100% of euthymic mice survived while all nude mice died. Post sulfadiazine treatment survival was enhanced in nude mice by reconstitution with either L3T4+ or Lyt-2+ cells and was reduced in euthymic mice by monoclonal antibody treatment directed at depleting either L3T4+ or Lyt-2+ cells or interleukin-2 (IL-2) or interferon-gamma (IFN-gamma). These results suggest that although T cells and their products are not required for an initial response (survival) to treatment in acute experimental toxoplasmosis, survival off drug is strictly T cell-dependent. Optimal posttreatment survival appears to involve both L3T4+ helper and Lyt-2+ cytotoxic cells, probably acting in concert, as well as the endogenous secretion of at least two T cell-derived lymphokines, IL-2 and IFN gamma. PMID- 8486952 TI - Heterogeneity in filarial-specific immune responsiveness among patients with lymphatic obstruction. AB - The relationship between chronic obstructive disease and antifilarial immune responsiveness was studied in the Haitian community of Leogane, where Wuchereria bancrofti is endemic. Differences in sex ratios and in the prevalence of microfilaremia were observed between patients with hydrocele and those with lymphedema or elephantiasis of the lower limb. Only 2 of 84 patients with limb involvement (74 women, 10 men) were microfilaremic compared with 25 of 42 men with hydrocele. Microfilaria-positive men with hydrocele had significantly lower IgG2 and proliferative responses to filarial antigen than did amicrofilaremic men with hydrocele or individuals with lymphedema or elephantiasis. Parasite-specific cellular responses of amicrofilaremic individuals with obstructive disease were greater, although not significantly so, than those of amicrofilaremic asymptomatic members of the community. These results are compatible with the hypothesis that development of obstructive disease of the lymphatics has an immune component in amicrofilaremic persons. PMID- 8486953 TI - Anti-gp160 IgG and IgA antibodies associated with a large increase in total IgG in cervicovaginal secretions from human immunodeficiency virus type 1-infected women. AB - To study the specific local immune response in vaginal fluids, 19 women infected with human immunodeficiency virus (HIV) type 1 and 23 seronegative controls were selected. Vaginal fluids were tested by ELISA for total IgG, IgA, and IgM levels and for specific IgG, IgA, and IgM antibodies to gp160. Total IgG, IgA, and IgM concentrations were 6.8-, 5.0-, and 2.5-fold higher, respectively, in HIV-1 infected women than in controls, with a positive correlation between IgG and IgA levels. IgG or IgA antibodies or both to gp160 were detected in 12 subjects (63%), whereas no IgM antibodies to gp160 were found. Anti-gp160 IgG strongly predominated. Serum samples were available for 11 women whose total IgG vaginal levels strongly correlated with total IgG in sera. These results suggest that transudation of serumborne antibodies is the main source of gp160-specific antibodies in the vaginal fluid of HIV-1-infected women. PMID- 8486954 TI - Acid dissociation of immune complexes improves diagnostic utility of p24 antigen detection in perinatally acquired human immunodeficiency virus infection. AB - Since acid treatment of serum is known to disrupt immune complexes, the diagnostic utility of the p24 antigen assay was examined after acid treatment of 345 serum samples from 158 children born to women infected with human immunodeficiency virus (HIV). Although the p24 antigen assay after acid treatment was negative in 9 HIV-1-infected children < 1 week old, antigen was detectable at high levels in all 30 samples obtained from infected children 1-9 months old. Overall, antigen was positive in 145 (sensitivity 89.5%) of 162 samples from 47 HIV-1-infected children > or = 1 month old. In contrast, the sensitivity of the p24 antigen assay without acid dissociation was only 18% (P < .001). Among the 76 uninfected children, 132 (specificity 99.2%) of 133 specimens were p24 antigen negative after acid dissociation. These results demonstrate that acid treatment of serum markedly improves the sensitivity and predictive value of the p24 antigen assay for diagnosis of perinatally acquired HIV-1 infection in children 1 month of age or older. PMID- 8486955 TI - Humoral immune response of humans to lipooligosaccharide and outer membrane proteins of Haemophilus ducreyi. AB - The humoral immune response to purified lipooligosaccharide (LOS) and outer membrane proteins (OMP) of Haemophilus ducreyi was evaluated. Sera from chancroid endemic (Uganda, Kenya) and -nonendemic (Canada) countries were tested by an ELISA. The response to OMPs was cross-reactive with other Haemophilus species, and elevated levels of antibody were detected in patients that did not have chancroid. The LOS component stimulated an H. ducreyi-specific immune response that was detected only in patients with chancroid. The sensitivity of the LOS ELISA was 96% (95% confidence interval, 89.9%-100%) and the specificity was 97% (95% confidence interval, 95.8%-98.2%). Thus, the anti-H. ducreyi LOS immune response is a significant diagnostic and epidemiologic indicator. PMID- 8486956 TI - Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with congenital asplenia. AB - The immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines in congenitally asplenic children is unknown. The short-term immunogenicity of the H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine was therefore assessed in 10 children with congenital asplenia by measuring antipolyribosyl-ribitol phosphate antibody titers. An excellent antibody response was seen in 9 children (mean geometric titer in responders after immunization 44.7 micrograms/mL; range, 2.59-402). The remaining child responded to a booster dose. Further studies are required to assess whether H. influenzae type b conjugate vaccines are immunogenic in infancy in the presence of congenital asplenia. PMID- 8486957 TI - Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization. AB - Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory. PMID- 8486958 TI - The vanB gene confers various levels of self-transferable resistance to vancomycin in enterococci. AB - Thirty-nine strains of Enterococcus faecium and Enterococcus faecalis resistant to vancomycin and susceptible to teicoplanin on disk susceptibility testing (phenotypic class B) were isolated in 15 hospitals in Europe and the United States. The MICs of vancomycin for these strains ranged from 4 to 1024 micrograms/mL. Part of the vancomycin resistance gene vanB from E. faecalis V583 hybridized with a single but variably sized HindIII-KpnI fragment of total DNA from all 39 strains. This indicates that a single class of resistance determinants accounts for the VanB phenotype. No hybridization was detected with DNA from intrinsically resistant Enterococcus gallinarum or Enterococcus casseliflavus. Hybridization with DNA from enterococcal strains susceptible to or with acquired resistance to vancomycin and teicoplanin was not observed. The genes conferring resistance to vancomycin were self-transferable to other Enterococcus strains in 14 of the 39 strains. It thus appears that vanB confers various levels of conjugative vancomycin resistance in enterococci. PMID- 8486959 TI - In vivo development of teicoplanin resistance in a VanB Enterococcus faecium isolate. AB - Acquired vancomycin resistance in enterococci may be associated with teicoplanin susceptibility (VanB) or teicoplanin resistance (VanA). This paper characterizes the first instance of in vivo emergence of teicoplanin resistance in an Enterococcus faecium strain of VanB phenotype. Vancomycin-resistant (MIC, 256/512 micrograms/mL) E. faecium was isolated intermittently from a patient's blood over 4 months. The MIC of teicoplanin for the first 5 isolates was 1.0 micrograms/mL; it was 64 micrograms/mL for the final 2. Analysis of plasmid and chromosomal DNA revealed the isolates to be of clonal origin. Conjugal transfer of vancomycin resistance was not obtained. A vanB DNA probe hybridized with both teicoplanin susceptible and resistant isolates, but a vanA probe failed to hybridize with any isolate. SDS-PAGE of membrane proteins from a teicoplanin-resistant isolate revealed constitutive production of a normally inducible 41-kDa protein. These findings challenge the ultimate utility of teicoplanin for treatment of infections caused by vancomycin-resistant enterococci. PMID- 8486960 TI - Typhoid fever at a resort hotel in New York: a large outbreak with an unusual vehicle. AB - The largest outbreak of typhoid fever in the United States since 1981 occurred in 1989 among guests and staff at a New York hotel. There were 43 culture-confirmed and 24 probable cases among guests, 1 culture-confirmed case and 1 asymptomatic culture-positive case among hotel employees, and 1 culture-confirmed secondary case. Twenty-one persons were hospitalized and 2 had bowel perforation. Breakfast on 13 June was the only meal consumed by all ill persons (relative risk, infinite; P = .004). In a case-control study, case-patients were more likely than controls to have consumed orange juice (odds ratio, 5.6; 95% confidence interval, 1.1-54.7), which had been prepared in a 208-L container with ample opportunity for hand contact. No other food was associated with illness. S. typhi was isolated from the stool of an asymptomatic food worker who handled orange juice but who was not known to be a typhoid carrier. S. typhi is a foodborne pathogen with continuing potential to cause large outbreaks in the United States. PMID- 8486961 TI - Direct inoculation of food as the cause of an outbreak of group A streptococcal pharyngitis. AB - An investigation was conducted of a food-related outbreak of group A streptococcal pharyngitis following an elementary school banquet. Of 166 surveyed banquet attendees, 71 (43%) reported outbreak-associated pharyngitis, and 21 (88%) of 24 tested attendees had evidence of group A streptococcus (GAS) in the throat. Attendees who ate macaroni and cheese were three times more likely to develop pharyngitis than those who did not (66/132 [50%] vs. 5/30 [17%], P = .002). None of the food handlers had GAS recovered by throat culture. However, the cook who prepared the macaroni and cheese had a hand wound; a wound culture grew GAS with the same T agglutination pattern and M- and/or opacity factor type as that of all available GAS strains from ill attendees. Under laboratory conditions, macaroni and cheese supported rapid growth of the outbreak-associated strain of GAS. To the authors' knowledge, this is the first documented foodborne outbreak of GAS pharyngitis in which the only apparent source of contamination was a food handler's skin lesion. PMID- 8486962 TI - Disparity of Borrelia burgdorferi infection rates of adult Ixodes dammini on deer and vegetation. AB - Rates of infection with Borrelia burgdorferi were compared in adult Ixodes dammini ticks collected from deer at one coastal and two island sites with those collected from vegetation at the same sites. Ticks were examined using polyclonal direct fluorescent antibody. Spirochetes were observed in 47% of 288 ticks from vegetation as opposed to 13% of 276 ticks from deer (chi 2, P < .001). This disparity was increased when only male ticks were compared. Among female ticks from deer, the infection rate was higher in flat than in engorged ticks. These findings may reflect spirochete loss from ingestion of borreliacidal antibodies in deer blood or may result from factors related to the sensitivity of direct fluorescent antibody methods. They indicate that erroneously low estimates of regional risk for Lyme disease may be obtained if ticks removed from deer are included in the determination of tick infection rates. PMID- 8486963 TI - Postexposure prophylaxis against experimental inhalation anthrax. AB - Inhalation anthrax is a rare disease that is almost invariably fatal. This study determined whether a prolonged course of postexposure antibiotics with or without vaccination would protect monkeys exposed to a lethal aerosol dose of Bacillus anthracis when the antibiotic was discontinued. Beginning 1 day after exposure, groups of 10 animals were given penicillin, ciprofloxacin, doxycycline, doxycycline plus vaccination, vaccination alone, or saline. Antibiotics were administered for 30 days and then discontinued. Vaccine was given on days 1 and 15. Two animals died of causes other than anthrax and were not included in the statistical analysis. Nine of 10 controls and 8 of 10 animals given only vaccine died. Each antibiotic regimen completely protected animals while on therapy and provided significant long-term protection upon discontinuance of the drug (penicillin, 7 of 10 survived, P < .02; ciprofloxacin, 8 of 9 survived, P < .002; doxycycline, 9 of 10 survived, P < .002; doxycycline plus vaccination, 9 of 9 survived, P < .0002). Protection against rechallenge was provided by combining postexposure antibiotic treatment with vaccination. PMID- 8486964 TI - Geographic variation in the humoral response to Pneumocystis carinii. AB - The reported incidence of Pneumocystis carinii pneumonia varies in different areas of the world, but little is known about geographic variation in the antibody response to specific antigens. The frequency of anti-P. carinii antibodies in the serum of normal and human immunodeficiency virus (HIV)-infected individuals from five different regions was compared. Serum specimens from 948 subjects were assayed for IgG antibodies to human-derived P. carinii by Western blot. The overall prevalence of anti-P. carinii antibodies was 72.9%. Among HIV seronegative individuals, the rate of seropositivity was similar in all regions (70.5%-82.4%). Antibodies to the 30- to 40-kDa antigen were most commonly detected. The frequency of antibodies to high-molecular-mass antigens (95, 120, and > 120 kDa) demonstrated significant geographic variation. This study demonstrates that antibody responses to P. carinii are common in all areas studied but vary in frequency and pattern. PMID- 8486965 TI - Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System. AB - To identify pathogens causing nosocomial fungal infections and the secular trend in their incidence in US hospitals, data from the National Nosocomial Infections Surveillance System, 1980-1990, were analyzed. During that period, 30,477 fungal infections were reported. The rate rose from 2.0 to 3.8 infections/1000 discharges. The highest number of nosocomial fungal infections/1000 discharges was reported from the burn/trauma service (16.1). Candida albicans was the most frequently isolated fungal pathogen (59.7%), followed by other Candida species (18.6%). The rate increased at all four major anatomic sites of infection. Patients with bloodstream infections who had a central intravascular catheter were more likely to have a fungal pathogen isolated than were other patients with bloodstream infection (relative risk = 3.2; P < .001): 29% of fungemia patients and 17% of patients with bloodstream infection due to other pathogens died during hospitalization (P < .001). Fungi are emerging as important nosocomial pathogens and control efforts should target fungal infections, especially fungemia. PMID- 8486966 TI - Increased exposure to cryptosporidia among dairy farmers in Wisconsin. AB - Cryptosporidium infection is an important cause of diarrhea in humans and livestock; no effective therapy is known. A self-administered questionnaire and an ELISA were used to assess the risk of exposure to cryptosporidia among 70 dairy farmers and 50 who were not dairy farmers in Wisconsin. Dairy farmers (44.3%) were more likely to be seropositive for cryptosporidia than were other persons (24.0%; relative risk = 1.9). Among dairy farmers, age > or = 50 and use of a canister method of milking were associated with seropositive status. Among persons who were not dairy farmers, feeding or milking cows was associated with being seropositive. These findings suggest that dairy farmers and other persons who have contact with cattle are at greater risk of Cryptosporidium infection than are persons who do not have such contact. Identification and avoidance of farming practices associated with Cryptosporidium infection may reduce the risk of infection among dairy farmers. PMID- 8486967 TI - Human immunodeficiency virus transmission and oral contraceptives. PMID- 8486968 TI - Fever and infection in the age since Wunderlich. PMID- 8486969 TI - Racial differences in serum beta 2-microglobulin in persons with human immunodeficiency virus infection. PMID- 8486970 TI - Gastrointestinal carriage of Listeria monocytogenes in household contacts of patients with listeriosis. PMID- 8486971 TI - Bactericidal activity of human sera against a Brazilian purpuric fever (BPF) strain of Haemophilus influenzae biogroup aegyptius correlates with age-related occurrence of BPF. PMID- 8486972 TI - Role of superantigens in human disease. AB - Superantigens include bacterial products (mainly of streptococci and staphylococci) that stimulate T cells to proliferate nonspecifically through interaction with class II major histocompatibility complex products on antigen presenting cells and then with variable regions on the beta chain of the T cell receptor complex. They include pyrogenic toxins (streptococcal scarlet fever toxins of serotypes A, B, and C, toxic shock syndrome toxin 1, and staphylococcal enterotoxin serotypes A, B, Cn, D, E, and G), streptococcal M protein, staphylococcal exfoliative toxin, and recently identified pyrogenic toxins made by groups B, C, F, and G streptococci and Streptococcus sanguis. Pyrogenic toxin superantigens cause acute toxic shock syndrome and are associated with toxic shock-like syndromes. Superantigens cause symptoms via release of immune cytokines. These proteins should be considered potential causes of illnesses such as rheumatic fever, arthritis, Kawasaki syndrome, atopic dermatitis, and guttate psoriasis because of their potent immune system-altering capacity. PMID- 8486974 TI - [Epidemiology of Tsutsugamushi disease and typing of isolated Rickettsia in Chiba Prefecture]. AB - In Chiba Prefecture, the first patient of Tsutsugamushi disease was found in the southern part in the 1950's, but after that no patient was detected until 1982. After 1982, patients have been noticed again, the number of patients has been increasing year by year. The number of serologically confirmed cases was 152 and 157 in 1989 and 1990, respectively with indirect immunofluorescence assay. About 90 percent of the patients were found in November and December, prevalently in the southern part of the prefecture. On the other hand, a few patients were found yearly in a harf of towns and villages in this prefecture. The number of isolated strains of Rickettsia tsutsugamushi from patients was 4, i.e., TR6030, TR6310, TR6311, and TR6324 in 1986 and 3, TR1811, TR1827 and TR1829, in 1991. Six isolates except TR6303 reacted with anti-Kawasaki monoclonal antibody but not with other strain specific monoclonal antibodies. Therefore, these 6 isolates were determined as Kawasaki type strain. An isolate. TR6303, reacted with anti Kuroki monoclonal antibody at a titer of 1:2560 and anti-Karp monoclonal antibody at a titer of 1:320. This result suggested that the recent Tsutsugamushi disease is mostly caused by Kawasaki types in this prefecture. PMID- 8486973 TI - [Investigation on immunological factors of non- and low-responders to hepatitis B vaccine]. AB - We investigated the immunological factors concerning the backgrounds of non- and low-responders who could not respond well to the hepatitis B (HB) vaccine. We injected 10 micrograms of the recombinant HB vaccine to the medical staffs of our hospital intramuscularly three times, 199 subjects of whom could receive the full course of immunization with the HB surface (HBs) antigen. We found that 14 subjects were non-responders whose titer of HBs antibody was under the 1.9 cut off index (C.I.) examined by radioimmunoassay (RIA) and 47 ones were low responders whose titers were between 2.0 to 9.9 C.I. and the frequency of non- and low-responders was higher in males after the full course of HB vaccination. We chose 46 subjects and divided them into 4 groups according to the titer of HBs antibody at 8 and 28 weeks. We compared those groups to each other according to the amounts of total protein, gamma-globulin, IgG, IgA and IgM, numbers of peripheral white blood cells and lymphocytes, and percentages of peripheral lymphocyte and subsets of T cell including the examination by two-color flow cytometry using monoclonal antibodies. However we could not get any significant difference in any of those immunological factors by T assay. From these findings we suggest that the response to the HB vaccine does not depend on the quantity of the immunological factors before vaccination but on specific reactivity to HBs antigen after vaccination. PMID- 8486975 TI - [In vitro induction of chlorhexidine- and benzalkonium-resistance in clinically isolated Pseudomonas aeruginosa]. AB - A study was made on the MIC distributions of chlorhexidine and benzalkonium chloride against clinically isolated 178 strains of Pseudomonas aeruginosa to find out the existence of strains resistant to those disinfectants and also on the in vitro induction of resistance to both drugs. The MIC of chlorhexidine gluconate was found to be distributed from 78 to 625 micrograms/ml with a single peak at 312 micrograms/ml. All 178 strains of clinical isolates were sensitive to chlorhexidine and none could be induced to become chlorhexidine resistant in vitro, suggesting that P. aeruginosa can not easily acquire chlorhexidine resistance. On the other hand, the MIC of benzalkonium chloride was distributed in two peaks; one peak was benzalkonium sensitive at 625 micrograms/ml (150 strains/178 strains: 84.3%) and the another peak was benzalkonium resistant at 5,000 micrograms/ml (28 strains/178 strains; 15.7%). Six (4.0%) of the 150 benzalkonium sensitive strains acquired benzalkonium resistance by in vitro induction of resistance; the MIC of 5 strains increased from 625 micrograms/ml to 2,500 micrograms/ml and that of the residual 1 strain increased from 312 micrograms/ml to 1,250 micrograms/ml. However, no change of MIC was observed in 28 benzalkonium-resistant strains of clinically isolated P. aeruginosa by in vitro resistance induction. Strains with MIC more than 5,000 micrograms/ml could not be obtained at all. The results suggest that the benzalkonium resistance can be introduced in P. aeruginosa whereas the resistance-acquiring rate is low. These results suggest that chlorhexidine gluconate is the first choice for prevention of Pseudomonas infection in the hospital and benzalkonium is also useful in 0.5% solution is used. PMID- 8486976 TI - [A study on acid resistance of Helicobacter pylori]. AB - Physiological saline solutions, each adjusted to pH 1.0, pH 2.0 and pH 7.2, and added urea and urease inhibitor (Acetohydroxamic acid), were inoculated with a culture solution of Helicobacter pylori NCTC11637 strain derived from man, and allowed to react for 10, 30, 60 and 120 minutes. After five days of incubation on a blood agar medium, remaining viable H. pylori was counted. Survival of H. pylori was inadequate under the conditions of pH 1.0 and pH 2.0, but survival up to 120 min was observed on addition of urea. Further, on addition of urease inhibitor the survival time was reduced. H. pylori survived under the condition of pH 7.2 independent of addition of urea and urease inhibitor. Urea is essential for survival of H. pylori under strongly acidic conditions, and utility of urease inhibitor was observed for inhibition of survival of H. pylori. PMID- 8486977 TI - [Clinical efficacy of flomoxef in neonatal bacterial infection]. AB - One hundred and seventy one neonates were treated with flomoxef (FMOX) and the clinical efficacy and safety were evaluated. The ages of the patients ranged from 0 to 28 days, and their body weights from 450 to 4300 g. Dose levels were 12.4 to 24.9 mg/kg every 8 or 12 hours for 1 to 10 days. Fifty two patients who responded to the FMOX treatment included 5 neonates with sepsis, 17 with suspected sepsis, 9 with urinary tract infections, 12 with pneumonia, 8 with intrauterine infections, and 1 with omphalitis. The other neonates could not be retrospectively diagnosed as bacterial infections. Of 52 patients, clinical results were excellent in 15, good in 34, fair in 1, and poor in 2. And the FMOX treatment was effective in 13 out of 14 patients in which causative bacteria were identified. The drug was well tolerated, but 6 neonates out of 33 over 5 days old had diarrhea. From these results, empiric treatment with FMOX against neonatal bacterial infection was as clinically useful as that of combination with ampicillin and gentamicin or cefotaxime and ampicillin in our neonatal intensive care unit. But, as this study did not include neonate with meningitis, efficacy to meningitis was not evaluated. PMID- 8486978 TI - [Pleural washing with povidone-iodine for treatment of empyema]. AB - In this paper, we report two successful cases of empyema treated by pleural washing with povidone-iodine solution. In these two cases, empyema was caused by secondary infection of multi-drug resistant Pseudomonas aeruginosa. First, we replaced intrathoracic drainage tube and washed intrathoracic space with 500-1000 ml saline containing antibiotics (tobramycin, aztreonam) every 8 hours for 10-14 days. But, cultural studies of pleural effusion were positive even after this treatment. So, we tried pleural washing with warm povidone-iodine solution 1:20 diluted with saline every 8 hours. Surprisingly, after 3 days treatment, cultural studies of the pleural effusion became negative. This pleural washing method with povidone-iodine was very effective for treatment of empyema patients. PMID- 8486979 TI - [Relationship between coagulase toxin-type and drug susceptibility in Staphylococcus aureus strains isolated in all the Japanese National University Hospitals]. AB - Drug susceptibility of 430 Staphylococcus aureus strains isolated in 1991 from clinical specimens at all of the Japanese national university hospitals was evaluated in relationship with the epidemiological markers, namely, coagulase typing, and staphylococcal enterotoxins (SE) and toxic shock syndrome toxin 1 (TSST-1) production. There were five major methicillin-resistant Staphylococcus aureus (MRSA) groups in all the 252 MRSA strains: coagulase-type II-SEC + TSST-1- producing strains (II-SEC + TSST-1): 34.5%; coagulase-type II-no toxin-producing strains (II-): 15.4%; coagulase-type IV-SEA-producing strains (IV-SEA): 10.3%; coagulase-type II-SEA + SEC + TSST-1- producing strains (II-SEA + SEC + TSST-1): 8.7%; and coagulase-type III-no toxin-producing strains (III-): 7.1%. II-SEA + SEC + TSST-1 group was highly resistant to OFLX, whereas half of the other strain groups were sensitive to OFLX. Seventy-eight percent of the IV-SEA group was sensitive to FMOX, but there was no sensitive strain to FMOX in the II-SEA + SEC + TSST-1 group. More than 50% of the IV-SEA, III- and II-groups were sensitive to IPM, while the II-SEC + TSST-1 and II-SEA + SEC + TSST-1 groups were highly resistant to IPM. The III- and II-groups showed very good sensitivity to MINO, but the sensitivity to it of the II-SEA + SEC + TSST-1 group was very low. All of the strain groups were sensitive to ST except for the IV-SEA group. These results may provide useful information in the choice of antibacterial agents for MRSA infection. PMID- 8486980 TI - Successful antifungal treatment of disseminated candidiasis associated with ARDS. PMID- 8486981 TI - [Case report of toxic shock-like syndrome due to group A streptococcal infection]. AB - A case of streptococcal toxic shock like syndrome occurring in a 44-year-old previously healthy Japanese male is reported. He initially had a sore throat, low grade fever, diarrhea and mild pains in a lower extremities. Shortly thereafter, he rapidly developed a high fever, profound hypotension, multifocal epidermal necrosis, and sever purulent fasciitis and myositis in both lower extremities, which required above knee amputation of both legs. He later developed disseminated intravascular coagulopathy, adult respiratory distress syndrome, acute renal failure, coma and necrotizing inflammation of both arms and external genitalia despite treatment. He died on the 13th hospital day. Streptococcus pyogenes was isolated from the necrotic muscles and right knee joint. The organism was typed as M3, T3, was sensitive to penicillins, and was found to be producing streptococcal pyogenic exotoxin A in vitro. This is the first case report of streptococcal toxic shock like syndrome in Japan. PMID- 8486982 TI - ECG of the month. One shot, two birds. Narrow QRS tachycardia. PMID- 8486983 TI - Caustic ingestion and esophageal injury. AB - This article reviews esophageal anatomy and the physiology of swallowing. A discussion of the epidemiology, pathology, evaluation, and management of patients with esophageal injury secondary to caustic ingestion is presented. PMID- 8486984 TI - Passive smoking and lung cancer. AB - The findings of a multicenter national study of lung cancer in lifetime-never smokers are reported. An increased lung cancer risk of approximately 30% was found among women whose husbands smoked. Elevated risks of 40% to 60% were also found associated with workplace exposures and other exposures outside the home. The findings of this study have been included in the recent Environmental Protection Agency assessment of the health effects of passive smoking, and have implications for regulation of environmental tobacco smoke exposure in Louisiana. PMID- 8486985 TI - Cancer awareness and attitudes toward preventive health behavior. AB - Elevated rates of morbidity and mortality among ethnic minorities have been linked to alterable patterns of behavior, including preventive health practices. African Americans in Louisiana are not only at increased risk for cancer, they also have poorer prognosis. This investigation describes beliefs, knowledge, and attitudes relevant to general and cancer-specific preventive health practices in a sample of African Americans (n = 48). Findings suggest a number of important differences exist between males and females in their attitude toward health issues. Females valued and expressed greater concern over their health status. Females also expressed greater confidence in their doctor's ability to diagnose cancer before it is too serious, while males appear to hold a more pessimistic view of the effectiveness of early detection. Although the use of a convenience sample limits the generalizations that can be made, present findings identify issues germane to the development of effective intervention strategies for this population. PMID- 8486986 TI - Breast Cancer Prevention Trial update. AB - In April 1992, the National Surgical Adjuvant Breast and Bowel Project and the National Cancer Institute launched the Breast Cancer Prevention Trial. This is the largest cancer prevention trial ever attempted. The Breast Cancer Prevention Trial will involve 16,000 high-risk women in the United States and Canada. Half will receive tamoxifen and half placebo. Currently, over 5,000 women have been enrolled in the Breast Cancer Prevention Trial. The Ochsner Community Clinical Oncology Program in New Orleans is coordinating the trial in Louisiana and Mississippi. Other participating centers in this area are located in Baton Rouge, Houma, and New Orleans East in Louisiana, and Biloxi, Gulfport, Hattiesburg, and Jackson in Mississippi. PMID- 8486987 TI - Childhood nasopharyngeal carcinoma. AB - A retrospective analysis identified 40 children and adolescents with nasopharyngeal carcinoma who were evaluated and treated at the Medical Center of Louisiana from 1948 through 1992. The male to female ratio was 1.8:1. Thirty-two patients had lymphoepithelioma and 8 had squamous cell carcinoma. Twenty-three children had primary lesions confined to the nasopharynx. In 8 patients, the tumor extended into the nasal cavity or oropharynx, and 7 patients had tumor invasion of skull or cranial nerve. Thirty-one had palpable cervical lymphadenopathy. There were no documented distant metastasis at presentation. All patients were treated with primary radiotherapy, and 9 patients also had chemotherapy containing cisplatin, fluorouracil, bleomycin, cyclophosphamide, and doxorubicin. Ten are alive 5 to 30 years from time of diagnosis (median 10 years). Distant metastasis was the initial cause of failure. Though not a controlled study, bias in the data insinuate an improved prognosis for male patients, age > 10 years, tumor limited to the nasopharynx without extension (T1 2), absence or single positive homolateral node (N0-1), and patients who received chemotherapy. PMID- 8486988 TI - Evidence for a major gene effect in early-onset lung cancer. AB - Genetic segregation analyses that allowed for variable age of onset of lung cancer and smoking history were performed on 337 families, each ascertained through a lung cancer patient. Results indicated compatibility of the data with Mendelian codominant inheritance of a rare major autosomal gene that acts in concert with smoking to predispose carriers to lung cancer, by producing earlier onset of the cancer when controlling for equivalent smoking levels. Segregation at this locus could account for 69% and 47% of the cumulative incidence of lung cancer in individuals up to ages 50 and 60 respectively, but only 22% of all lung cancers in persons up to age 70. This decrease in the importance of the gene's contribution to overall lung cancer rates at later ages is most likely a reflection of an increasing proportion of noncarriers succumbing to the effects of long-term exposure to tobacco. A significant cohort effect was found, most likely due to differing smoking patterns before and after World War I, but in both cohorts the effect of a major locus could not be rejected. PMID- 8486989 TI - Is breast preservation possible in women with large, locally advanced breast cancers? AB - Breast conservation therapy is an accepted treatment option for early stage breast carcinoma, but is rarely considered appropriate for locally advanced nonmetastatic lesions. Mastectomy specimens of 46/50 patients treated at the Ochsner Clinic and the Mallinckrodt Institute of Radiology with neoadjuvant chemotherapy prior to mastectomy +/- irradiation were evaluated by a single pathologist to assess tumor response to chemotherapy. Forty percent of this group would potentially have been eligible for breast conservation therapy, using a residual tumor size of < or = 4 cm with negative surgical margins as the criteria. Patients most likely to qualify for breast conservation therapy were those with T3N0-1 lesions (67%). Least likely were patients with skin involvement at diagnosis 4/33 (12%). Tumors with an extensive intraductal component at biopsy often had residual islands of intraductal carcinoma occupying the original tumor volume, even when the invasive component was absent or much reduced. A prospective trial will be required to determine whether or not acceptable local control rates can be obtained after breast conservation therapy for that subset of patients with a favorable response to induction chemotherapy. PMID- 8486990 TI - New agents for controlling emesis with cancer chemotherapy. AB - Over the past decade, marked progress in support techniques has been made in patients with cancer. In addition to improvement in pain and infection control, the ability to control chemotherapy-induced nausea and vomiting has improved greatly. Studies have demonstrated that serotonin type 3 receptors play an important role in mediating this side-effect. Several new agents, with excellent efficacy and few side effects have now been developed and are available clinically. Results of trials with these agents, and with newer investigative approaches are discussed. PMID- 8486991 TI - Cancer chemotherapy in historical perspective. AB - Effective systemic cancer therapy has evolved during the past 50 years. Prior to that time a variety of treatments were attempted, many of which seemed to have had their origins in sorcery rather than science. The 1950s and 1960s produced an explosion of knowledge and many of the chemotherapeutic agents in use today were synthesized during that time frame. Currently we are exploring a variety of new therapeutic approaches to cancer, and the future promises to be increasingly productive. PMID- 8486992 TI - Social skills in the context of learning disability definitions: a reply to Gresham and Elliott and directions for the future. AB - In this article we review the evidence on the status of a social skills deficit as a learning disability (LD) by examining social skills deficits in the context of learning disability definitions. For the most part, social skills deficits fall within the terms that are specified in the definitions; that is, when there is evidence of neurological involvement, social skills deficit as a learning disability is consistent with the focus on listening and speaking that is characteristic of most definitions of learning disabilities. We also conclude that the absence of limiting conditions in extant definitions of learning disabilities makes it difficult to exclude any particular skill or type of knowledge from falling within the bounds of the definitions. Furthermore, we argue that the critical issue centers on the reformulation of the definition of learning disabilities. We suggest two directions in future work: First, the term "learning disability" should be limited to intentional learning contexts. Acceptance of this limitation would clarify at least some of the confusion regarding the domain of learning disabilities. Second, learning disability definitions should become more responsive to recent research on the nature of learning. PMID- 8486993 TI - Adolescents with learning disabilities at risk? Emotional well-being, depression, suicide. AB - As recently as 5 years ago, very little information on the emotional well-being of adolescents with learning disabilities (LD) was available. However, a great deal of research has been conducted recently and some of the implications are unnerving. Research on self-concept, attributions, anxiety, depression, and suicide among adolescents with LD is examined for the purpose of detecting consistency of indicators concerning these emotional and developmental variables. The research indicates that the emotional development of many adolescents with LD is not notably positive, and these students appear to be at increased risk for severe depression and suicide. The discussion highlights methodological pitfalls and developmental issues. Practical implications are suggested. PMID- 8486994 TI - An examination of phonemic processing abilities in children during their first grade year. AB - The present study examined the development of reading and phonological processing abilities of 209 first graders (118 males, 91 females; mean age = 86.7 months) assessed during the first and last quarters of their first-grade year. The children were arranged into three different groups based on their Time 2 reading and intelligence data (children with and without reading disabilities, and "garden-variety" poor readers). Analyses indicated that the children with reading disabilities and the garden-variety poor readers did not differ significantly on many of the tasks, but both performed differently than the children without reading disabilities. Developmental analyses indicated that all three groups increased their reading and phonological skills; however, the gap between the performance of the children without reading disabilities and the other two groups widened from Time 1 to Time 2. The most important finding of the present study concerned the classification results of the discriminant analysis, which correctly identified the group membership of 207 of the 209 children (99.04% correct). PMID- 8486995 TI - The social misperception syndrome in children with learning disabilities: social causes versus neurological variables. AB - Family shortcomings or other intrinsic psychological deficits are frequently viewed as contributing factors to the social misperceptiveness frequently seen in children with learning disabilities. This article attempts to synthesize research defining the social problems of some children with learning disabilities. Particularly emphasized is the role of communication skills deficits. Breakthroughs in neurophysiology negate, to a large extent, traditional emphases on family dysfunction, school failure, or personality distrubances as primary causes of the social problems of some children with LD. Advances in vision and language research allow departure from the social paradigm of the "misperceptive syndrome" to consider constitutionally based hypotheses of neural dysfunction. Neural aberrations are viewed as triggering deficient language processing, which in turn may lead to unsatisfactory social interactions. Several correlates and characteristics of family, school, and environmental systems are discussed in the context of their impact on personality development and on changes in the life adjustments of both children and adults with learning disabilities. PMID- 8486996 TI - Which motoric condition is most effective for teaching spelling to students with and without learning disabilities? AB - The purpose of this study was to determine the efficacy of three motoric conditions (writing, tracing, and computer keyboarding) on the spelling performance of 24 third- and fourth-grade students without learning disabilities (NLD) (15 males, 9 females) and 24 third- and fourth-grade students with learning disabilities (LD) (16 males, 8 females). This study applied empirically based procedures for teaching spelling, examined student performance over time, and incorporated student interviews concerning their preference for motoric condition. For number of words spelled and proportion of bi-grams (correct letter sequences) used correctly, significant differences were found between the LD and NLD groups, both at posttest and follow-up, with the NLD students learning to spell more words and apply more correct bi-grams than the students with LD. There was no significant effect for condition for either words spelled or bi-grams, indicating that students did not learn significantly more words in the writing, tracing, or computer condition. There was also a significant time effect indicating that the accuracy of both groups decreased over time from posttest to follow-up for both words and bi-grams. Interviews revealed that students in both groups preferred the computer condition; however, they believed that they learned best in the writing and tracing conditions. PMID- 8486997 TI - Supervision of employees with moderate special needs. AB - A study was conducted to identify issues that confront workplace supervisors of people with learning disabilities (LD): problem behaviors, supervisory techniques, and the supervisor's needs. Conclusions are based on questionnaire responses from 65 supervisors in human service agencies and 27 interviews conducted with employers and supervisors in business and industry. Findings indicate that this special needs population surpasses the general population in exhibiting several positive work habits. Problem behaviors are most commonly addressed by establishing realistic performance standards, being flexible, and modifying tasks. Training supervisors who provide specific information concerning the individual are a major source of support to the on-site supervisor. Supervisors felt that personal commitment to this population and availability of specific information concerning LD were the most important influences on the quality of their work with the trainee. Findings from this study hold hope for the successful employment of people with LD. PMID- 8486998 TI - Giant fiber activation of an intrinsic muscle in the mesothoracic leg of Drosophila melanogaster. AB - Cinematographic analysis reveals that an important component of the light elicited escape response of Drosophila melanogaster is the extension of the femur tibia joint of the mesothoracic leg. During the jumping phase of the response, this extension works synergistically with extension of the femur. Femur extension is generated by contraction of the tergotrochanteral muscle (TTM), one of four previously described escape response muscles. Femur-tibia joint extension in the mesothoracic leg has been thought to be controlled by contraction of the tibial levator (TLM), an intrinsic leg muscle. We investigated the activation of the TLM during the escape response. Electrical stimulation of the giant fiber interneuron that mediates the escape response results in activation of the TLM with a latency of 1.46 +/- 0.02 ms. The TLM is innervated by a motor neuron (TLMn) with a large cell body in the mesothoracic ganglion. The TLMn has extensive arborizations in the lateral mesothoracic leg neuromere and has a prominent medially directed neurite. To investigate possible presynaptic inputs activating the TLMn during the escape response, we analyzed the muscle responses of two mutants, giant fiber A1 and bendless. Our analysis suggests that the TLMn is activated by a novel pathway. PMID- 8486999 TI - The regulation of haemolymph potassium activity during initiation and maintenance of diuresis in fed Rhodnius prolixus. AB - The blood-sucking insect Rhodnius prolixus rapidly eliminates a Na(+)-rich K(+) poor urine after its large meals. K(+)-rich fluid is first secreted by the upper Malpighian tubules and passes to the lower tubules where most of the potassium is reabsorbed. During the initial stimulation of the tubules, the lower tubules must be activated first to avoid loss of potassium. The major element in this is that they respond more rapidly than do the upper tubules to particular hormonal concentrations rather than that they react to lower hormonal concentrations than do the upper tubules. During subsequent diuresis, regulation of the haemolymph potassium concentration depends on three cooperative homoeostatic mechanisms in the tubules. A fall in potassium concentration of the medium bathing the tubules causes (i) a decrease in the rate of fluid secretion by the upper tubules, (ii) a decrease in potassium concentration in the fluid secreted by the upper tubules and (iii) an increase in the rate of potassium absorption by the lower tubules. The tubules respond in the opposite direction to an increase in potassium concentration of the medium. As a result, the potassium concentration of the urine can be adjusted to match the potassium concentration of the fluids absorbed from the gut, so that the potassium concentration of the insect's haemolymph remains unaltered. PMID- 8487000 TI - Effect of adenosine on glucose metabolism of Rana ridibunda erythrocytes. AB - The effects of adenosine and inosine on Rana ridibunda erythrocyte metabolism were studied. Adenosine can be metabolized by Rana ridibunda erythrocytes as a carbon source for glycolysis to maintain ATP levels, whereas neither inosine nor glucose could maintain ATP levels. The rate of lactate production was maximal (2.89 mumol ml-1 red cell h-1) in the presence of adenosine together with glucose compared with that in the presence of glucose or adenosine alone. Inosine sustained a similar rate of lactate production as did glucose. The concentrations of phosphorylated hexoses increased during 4 h of incubation in the presence of adenosine either with or without glucose. The presence of sodium iodoacetate accelerated the loss of ATP; furthermore, levels of lactate and pyruvate were significantly reduced in the presence of either adenosine or inosine. Ouabain strongly inhibited ATP and lactate formation in the presence of adenosine, whereas the levels of ATP and lactate were almost unchanged in the presence of inosine. An inhibitor of adenosine transport, dipyridamole, impeded the increases in erythrocyte lactate and ATP concentration in the presence of adenosine but did not modify the effects of inosine. PMID- 8487001 TI - Animal versus vegetable protein diet in hepatic encephalopathy. PMID- 8487002 TI - Fibrillating atria--a sizeable problem, or rather atrial fibrillation--a striking problem. PMID- 8487003 TI - Haemostatic factors in coronary heart disease. PMID- 8487004 TI - Prognostic significance of type and location of a first myocardial infarction. AB - The prognostic significance of type (Q-wave versus non-Q-wave) and location of infarction (anterior versus infero-posterior) was assessed in 350 patients with a first myocardial infarction followed for 3 years. A baseline multivariate Cox model was constructed from variables assessable at entry of the index infarction. The prognostic significance of site and type of infarction was evaluated when added to this model. Both Q-wave infarction and anterior location were significant with a risk ratio of 1.91 (95% confidence interval 1.14-3.18) and 1.70 (95% confidence interval 1.11-2.61) respectively. However, when the model also included the size of infarction. Q-wave infarction was no longer formally significant, while anterior location still was associated with adverse outcome (risk ratio 1.56, 95% confidence interval 1.02-2.39). It is inferred from the results that this effect of anterior infarction is due to a larger damage to the left ventricle for identical infarct sizes compared to infero-posterior infarctions. PMID- 8487005 TI - Monitoring of hearing during treatment of leukaemia with special reference to the use of amikacin. AB - Thirty-nine patients with leukaemia were followed audiometrically during treatment with broad-spectrum antibiotics. Amikacin was given during neutropenic febrile episodes. Five patients reported a deterioration of the hearing function after termination of amikacin treatment. Significant hearing threshold loss occurred in 20 patients (51%). The hearing threshold changes were small in general, except for two patients who exhibited bilateral hearing threshold changes in the frequency range 0.5-8 kHz. Using multiple linear regression analysis 22% of the changes in hearing thresholds was estimated to be related to old age, an increased trough concentration of amikacin and an impaired pretreatment hearing state. Factors found not to influence the hearing thresholds were maximum peak concentration of amikacin, cumulative duration of therapy, pretreatment renal dysfunction and concomitant use of vancomycin. It is concluded that administration of amikacin for repeated treatment courses is associated with a low incidence of serious changes in hearing function. PMID- 8487006 TI - Metabolic effects of strict salt restriction in essential hypertensive patients. AB - OBJECTIVE: Some observations suggest that a strict low-salt diet may induce unfavourable metabolic side-effects. The main aim of this study was to analyse the possible consequences of severe salt restriction in mildly hypertensive patients. DESIGN: The study was carried out through a randomized double-blind protocol. SUBJECTS: Forty-seven ambulatory patients proceeding from the hypertension unit were initially admitted: 17 were lost, and 30 non-diabetic mildly hypertensives (DBP 90-104 mmHg) with normal renal function completed the protocol. INTERVENTION: After a wash-out period, patients were maintained on a low-salt intake (2.8 +/- 1.0 g day-1 of NaCl) and placebo for 2 weeks, and the same diet and salt supplements (11.7 +/- 2.5 g day-1 of NaCl) for another 2 weeks, separated by a second wash-out period. MEASURES: At the end of each dietary period, blood pressure (BP) and body weight were measured, and a blood sample was taken for determination of routine serum chemistries, plasma lipid and apolipoprotein concentrations, immunoreactive insulin (IRI), and plasma renin activity (PRA). Urinary 24 h excretion of sodium and potassium were measured. RESULTS: During the salt restriction period BP did not change, weight lowered, and PRA raised. There was a significant increase in serum level of creatinine, uric acid, IRI, total cholesterol and apo B, and a decrease in HDL cholesterol and apo A-I. CONCLUSION: As previously suggested, these observations seem to indicate that strict salt restriction may cause, at least in the short-term, adverse metabolic changes in hypertensive patients. PMID- 8487007 TI - Supraventricular tachycardia, right atrial pressure, atrial natriuretic peptide and polyuria--a necessary sequence? AB - The release of atrial natriuretic peptide (ANP) may be stimulated by tachycardia and the evidence from human studies suggests that this is mediated by a rise in atrial pressure. However, animal experiments suggest that tachycardia can by itself increase ANP levels without increasing right atrial pressure (RAP). We report here the case of a healthy volunteer who had supraventricular tachycardia (SVT) whilst participating in a study evaluating the relationship between changes in RAP and changes in ANP. The ANP levels rose following the SVT but there was no rise in RAP, suggesting that heart rate can modulate ANP levels without changes in RAP as has been shown in animal experiments. PMID- 8487008 TI - Pyomyositis in a patient with myeloma responding to antibiotics alone. AB - Pyomyositis is a rare purulent infection of skeletal muscle with striking clinical features. It usually occurs in patients living in the tropics but is increasingly being reported in immunosuppressed patients. The traditional approach to management has been surgical with drainage and debridement of the multiple muscle abscesses. We report a patient with myeloma who developed multiple muscle and lung abscesses associated with a Staphylococcus aureus septicaemia. The case was successfully managed with intravenous antibiotics alone with no recurrence of the abscesses during a later episode of neutropenia. The advantages of avoiding surgical intervention in immunosuppressed and thrombocytopenic patients are obvious. PMID- 8487009 TI - Past and present problems in editing medical journals. PMID- 8487010 TI - von Willebrand factor antigen, atherothrombotic mechanisms and smoking. PMID- 8487011 TI - Global myocardial ischaemia unmasked following a bomb attack. PMID- 8487012 TI - The interaction between allopurinol and azathioprine. PMID- 8487013 TI - Sjogren's syndrome, primary biliary cirrhosis and overlap with scleroderma symptoms. PMID- 8487014 TI - Maintenance of high extracellular pH does not influence cell pH or metabolism in submerged anoxic bullfrogs. AB - We compared extracellular and intracellular acid-base states in paralyzed bullfrogs subjected to 4 h of anoxic submergence at 15 degrees C with or without maintenance of extracellular pH at preanoxic levels by bicarbonate infusion. We also assessed anaerobic metabolism under these conditions by measuring tissue lactate and glycogen concentrations in liver, heart, and skeletal muscle. Although bicarbonate infusion resulted in a significantly higher arterial blood pH (pHe) than saline infusion, intracellular pH (pHi) of heart and skeletal muscle, as determined by the DMO equilibration technique, were not significantly different after 4 h of anoxia. We were also unable to demonstrate any differences in anaerobic metabolic rate, since both tissue lactate accumulation and glycogen depletion were identical in bicarbonate- and saline-infused frogs in the tissues studied. We conclude that (1) alterations in the extracellular acid-base state by bicarbonate infusion are not necessarily reflected in the intracellular compartment, perhaps due to powerful intracellular buffering processes, and (2) maintenance of an alkaline extracellular pH during anoxia in bullfrogs does not influence the anaerobic metabolic rate. We could not, however, rule out a possible role for intracellular pH in regulating anaerobic metabolism during anoxia in frogs. PMID- 8487015 TI - In vitro exposure of frog (Rana pipiens) pituitaries to gonadotropin-releasing hormone results in a persistent stimulation of gonadotropin biosynthesis. AB - To further investigate the action of gonadotropin-releasing hormone (GnRH) on gonadotropin (Gth) secretion and synthesis, pituitaries from frogs, Rana pipiens, were incubated in the presence or absence of 100 ng/ml GnRH for 12 h. GnRH was then removed from the medium and glands were labeled with 35S-methionine either 12, 24, or 36 h after the conclusion of GnRH exposure. Immunoassayable LH and FSH (iLH and iFSH; both labeled and nonlabeled hormone) were determined by separate radioimmunoassays. Newly synthesized (radiolabeled) Gth was quantified by immunoprecipitation. When GnRH was present in the medium, it stimulated the secretion of both iLH and iFSH (compared to unexposed glands). Following withdrawal of the secretagogue, iLH and iFSH secretion diminished until they returned to control levels (within ca. 12 h). Previous exposure to GnRH enhanced the biosynthesis of Gth; this elevation was detectable up to 36 h after removal of the secretagogue. The magnitude of the elevation in Gth synthesis did not diminish with time, as secretion had, but remained constant. Gth synthesis was comparable in glands that had been exposed to GnRH 12 h and those exposed to the secretagogue 36 h prior. Thus, the GnRH-induced elevation in Gth secretion and synthesis can be dissociated; the elevation in synthesis is more chronic than the elevation in secretion. PMID- 8487016 TI - Cloning and chromosomal mapping of mouse seminal vesicle protein F. AB - Seminal vesicle proteins (SVPs) are made by male rodents, and form the copulatory plug following mating. Here we report a partial nucleotide sequence of a mouse clone homologous to rat SVP F. Unexpectedly, we found that SVP F-related transcripts are expressed at high levels in mouse skeletal muscle. We mapped mouse SVP F to mouse chromosome 15 using somatic cell hybrid lines. PMID- 8487017 TI - Distribution of lectin binding sites in the oviducts of cycling and hormone treated pigs. AB - Gamete transport, fertilization, and early embryonic development take place in different regions of the oviduct and under different hormonal conditions. The objective of this study was to use lectins to detect variation in the distribution of glycosylated molecules on the surface of the epithelia that influence these events. Oviducts were collected from gilts on day 1 (estrus) and day 16 (diestrus) of the estrous cycle, and from gilts that were bilaterally ovariectomized on day 4 of the estrous cycle, and were subsequently treated with estradiol valerate (100 micrograms/day), progesterone (200 mg/day), or corn oil vehicle for 11 days. Six biotinylated lectins, Triticum vulgaris (WGA), Arachis hypogaea (PNA), Ulex europeus (UEA-I), Dolichos biflorus (DBA), Ricinus communis (RCA-I), and Canavalia ensiformis (Con A), were used to probe tissue from the isthmus and ampulla using peroxidase-conjugated avidin as the marker. In cyclic gilts, WGA and DBA stained more strongly in the isthmus than the ampulla on both cycle days. Staining with PNA was patchy, but greater on the apical surface of isthmic epithelium on day 16 than day 1. With UEA-I, staining was more intense in the ampulla on day 16 than day 1. Staining by PNA and UEA-I was suppressed in both the ampulla and isthmus with estradiol treatment. DBA staining was suppressed in the isthmus with both estradiol and progesterone treatments. Cilia were labelled by all lectins except WGA and PNA. Thus glycosylation patterns vary in the porcine oviduct with region and hormonal state, reflecting the variety of events that may be influenced. PMID- 8487018 TI - Temperature-dependent sex determination in the leopard gecko, Eublepharis macularius. AB - The leopard gecko, Eublepharis macularius, has temperature-dependent sex determination (TSD). Previous reports have shown that females are produced predominantly at cool incubation temperatures and males are produced predominantly at warm incubation temperatures (Pattern Ib). We report here that incubation at even higher temperatures (34 and 35 degrees C) produces mostly females (Pattern II). The lethal maximum constant incubation temperature for this species appears to be just above 35 degrees C. Although a previous study indicated that females from a warm incubation temperature (32 degrees C) failed to lay eggs, we found that 12 of 14 mature females incubated at 32.5 degrees C, and 5 of 6 mature females incubated at 34 degrees C produced fertile eggs and viable hatchlings. PMID- 8487019 TI - Stand united together. PMID- 8487020 TI - Potent ammunition. PMID- 8487021 TI - Like people, schools face new challenges at 40. PMID- 8487023 TI - The physician as dog. PMID- 8487022 TI - Social change in medical practice in the 1990s. The "US" health care plan. PMID- 8487024 TI - Effect of undocumented and excluded vaccinations on measles immunity in a university population. AB - Epidemic measles has occurred even in highly vaccinated university and college populations because vaccine efficacy is only 90-95% and some student bodies do not have 100% vaccine coverage. Some institutions have not adopted or enforced a one-dose, preregistration immunization requirement because of the increased administrative burden, although in 1990 a documented two-dose schedule was recommended to increase herd immunity to a critical 93.5-96.0%. Perhaps one documented immunization for all students coupled with an undocumented or excluded pre-1968 one that some students are reporting will result in adequate herd immunity. At the University of South Florida 149 students (group I), after documenting receipt of one immunization, attempted to prove immunity by having an antibody test. They were compared with 181 students who documented two doses (group II) for factors which might influence differences of immunity between the groups after one dose. Undocumented immunizations were estimated by determining the percent of students reporting recent immunizations after allowing for the expected unimmunized percent. Excluded vaccinations were calculated for students born before 1967. Group I had a 98% (95% C.I. 94.2-99.6) immunity. One-third to one-half of both groups had undocumented and excluded immunizations. Some differences identified were not important enough to prevent extrapolation of this high immunity from group I to group II students. One documented live measles vaccination for all students combined with an undocumented or excluded one for some of them may provide adequate herd immunity to prevent measles epidemics on university and college campuses. PMID- 8487025 TI - Breast cancer screening in Florida. Opportunities for prevention. AB - Records of 705 women age 40 years and over interviewed by the Florida Behavioral Risk Factor Surveillance System in 1990 were used to identify gaps in mammography utilization in Florida. Data were weighted to the 1990 age and race composition of the population. Of the women 55.8% received a mammogram in the last two years and 33.4% reported they had never had one. The percentage reporting a mammogram in the last two years was 61.9% for those who had a check-up in the last year and 68.7% for those who had a breast examination in the last year. The reason 34% gave for not having a mammogram was "not recommended by doctor." Cost or lack of insurance was the reason for 10.6% of all women and 15.2% of women from households below $15,000 annual income. Data were further stratified by age and race/ethnicity. Significant missed opportunities for mammography are occurring among women in the health-care system. Interventions to increase mammography need to address providers' attitudes and behaviors as well as potential patients. PMID- 8487026 TI - Don't throw mama from the train. PMID- 8487027 TI - Regulating spermatogenesis. Mechanisms of reproductive hormones. PMID- 8487028 TI - Oral assessment in the elderly. AB - This review of common oral problems and oral assessment of the older adult is by no means exhaustive. There are a number of other oral manifestations of disease states that the physician can only assess by thorough examination of all structures and tissues in the mouth. By applying the simple principles of oral assessment and appropriate treatment and referral for common oral conditions, physicians can deliver optimum health-care services to the older adult patient. PMID- 8487030 TI - Breeder industry. PMID- 8487029 TI - Biomedical waste. PMID- 8487031 TI - First reported case. PMID- 8487032 TI - Future of health care in Florida. PMID- 8487033 TI - Blood groups and enzyme types from human teeth. AB - Paired human teeth and fresh blood samples were analysed for the genetic markers ABO, PGM1, GLO-I, EsD, EAP, AK, ADA, 6-PGD, G-6-PD and CA-II. ABO blood groups were successfully determined from dentine, pulp and cement samples whereas only dental pulp could be typed for different isozymes. Studies on the persistence of these genetic markers in teeth stored at room temperature showed that ABO blood groups were the most stable, followed by PGM1 and ADA isozymes, whereas CA-II isozymes were the least stable. PMID- 8487034 TI - Cases of fatal triazolam poisoning. AB - Benzodiazepines have been regarded as relatively safe drugs but since triazolam was introduced into Denmark in 1978, six fatal cases of poisoning by triazolam alone or in combination with ethanol, have occurred in East Denmark. In one case where no ethanol was detected, a blood triazolam concentration of 0.11 mg/l was found. In another case in which blood was unavailable because of putrefaction, muscle was analyzed. In the four cases in which the ethanol concentration was in the range 110-202 mg/100 ml, the triazolam concentration range was 0.04-0.22 mg/l. Blood concentrations from these five cases were compared to those from living persons who had also ingested the drug, and these were in the range 0.002 0.03 mg/l (n = 28), with an average concentration of 0.01 mg/l. PMID- 8487035 TI - Competitive EIA for anti-HIV-2 detection in The Gambia: use as a screening assay and to identify possible dual infections. AB - The performance of a competitive EIA for the detection of HIV-2-specific antibody utilising a viral lysate antigen was assessed over a 3 year period in The Gambia, West Africa, and compared with a commercially available assay, ELAVIA-2, using three panels of sera. An immunodominant region of the transmembrane glycoprotein of an HIV-2 isolate (ANT 53) was also cloned and expressed in E. coli as a beta galactosidase fusion protein and the resulting recombinant protein substituted in place of the existing viral lysate antigen. Competitive EIAs were found to be both a specific and sensitive means of reliably determining the HIV-2 status of an individual with a high predictive value, particularly when a strategy of concordant positive results in the two EIAs was used. When either anti-HIV-2 competitive EIAs were used in conjunction with a competitive EIA for anti-HIV-1 detection it was possible in the vast majority of cases to identify the virus type infecting an individual and speciate HIV-1 and HIV-2 infections. A few sera which showed similar regression profiles when diluted over a serial tenfold dilution steps were identified as possible dual infections. PMID- 8487036 TI - Assessment of the antibody response to the immunosuppressive/immunodominant region of HIV gp41 in a 5-year longitudinal study. AB - The antibody response of HIV-infected individuals to the 581-609 amino acid (aa) region of HIV-1 gp41 containing the putative immunosuppressive and immunodominant sequences was examined. Sera collected every 5 to 6 months over a period of 5 years from 50 HIV-1-infected homosexual and bisexual men, 25 of whom progressed to AIDS during the collection period, were monitored for changes in ELISA reactivity against synthetic peptides encompassing aa581-609 of gp41. The data obtained in this blinded, historical prospective study were analyzed with respect to changes in mean ELISA absorbance over time and differences in absorbance between patient groups (those who progressed to AIDS and those who did not). No correlation was found between time or disease state and the presence of antibodies to the aa581-597 immunosuppressive sequence. In contrast, ELISA absorbance against the aa598-609 immunodominant sequence continued to increase over time in both the AIDS and non-AIDS groups. The rate of increase in absorbance was similar for both groups; however, the AIDS group had a significantly higher mean absorbance level at the outset of the study and maintained this difference throughout the study. This region of gp41 has been proposed to play a role in complement-mediated antibody-dependent enhancement of infection. PMID- 8487037 TI - Dobrava virus as a new Hantavirus: evidenced by comparative sequence analysis. AB - Dobrava virus, recently isolated from a yellow-neck mouse (Apodemus flavicollis), captured in a northern Slovenian village where severe cases of hemorrhagic fever with renal syndrome were recognized, was shown by serology and restriction enzyme digestion of PCR-amplified gene segments to be related to previously recognized hantaviruses. To investigate further the relationship of this new isolate to other hantaviruses, a portion of the medium (M) genome segment of Dobrava virus was amplified by PCR and the nucleotide sequence determined. Comparing the nucleotide sequence with the same gene region of other hantaviruses revealed an overall homology of 41.7%. A phylogenetic tree based on pairwise sequence similarity clearly showed that Dobrava virus is genetically distinct, and probably represents a new virus in the genus Hantavirus of the family Bunyaviridae. PMID- 8487038 TI - Hepatitis A causing a second episode of virus-associated haemophagocytic lymphohistiocytosis in a patient with Still's disease. AB - A 20-year-old female with Still's disease who had contracted hepatitis A became critically ill 2 weeks after the onset of jaundice with pancytopenia, coagulopathy, deteriorating liver function tests, and hepatomegaly. The diagnosis of virus-associated haemophagocytic lymphohistiocytosis was made, and she improved slowly after supportive treatment with parenteral steroids and immunoglobulin. Twelve years earlier, at the onset of her arthritis, she had suffered a similar episode of haemophagocytic lymphohistiocytosis in association with Epstein-Barr virus infection. PMID- 8487039 TI - Identification and use of a neutralising epitope of parvovirus B19 for the rapid detection of virus infection. AB - A conserved neutralising epitope was confirmed as the site of specific activity for the monoclonal antibody R92F6. This monoclonal antibody was used to detect B19 viral antigen in serum samples after SDS-PAGE and Western blotting. Twenty samples from the United Kingdom, Ireland, Japan, and the United States were positive with this technique. Serum samples from various control groups were negative. PMID- 8487040 TI - Preparation, characterization, and antitumor activity of new ethylenediamine platinum(IV) complexes containing mixed carboxylate ligands. AB - A series of ethylenediamine platinum(IV) complexes of the type PtIV(en)XA2 and PtIV(en)X'2A2, where X = 1,1-cyclobutanedicarboxylato or malonato, X' = chloro, cyclobutanecarboxylato, cyclopentanecarboxylato, or cyclohexanecarboxylato, and A = acetato or trifluoroacetato were synthesized and characterized by elemental analysis, infrared, and NMR (13C and 195Pt) spectroscopic techniques. These compounds had good to excellent antitumor activity against murine leukemia L1210 cells. Complexes with axial trifluoroacetate groups were superior to those with acetate ligands. Those possessing both axial trifluoroacetate groups and monodentate bis-carboxylate ligands in the equatorial positions were the most active in the series investigated. PMID- 8487041 TI - Nursing in Europe towards the 3rd millennium. Report of the CICIAMS European Seminar, Edinburgh, Scotland. PMID- 8487042 TI - Relationship between tumor area, tumor volume, and criteria of response in clinical trials. PMID- 8487043 TI - A cry from the fringe. PMID- 8487044 TI - Regional hepatic arterial chemotherapy for colorectal cancer metastatic to the liver: the controversy continues. PMID- 8487045 TI - Back to the basics: the importance of concentration x time in oncology. PMID- 8487046 TI - Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia. AB - PURPOSE: Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial. PATIENTS AND METHODS: Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54. RESULTS: Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (> 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR. CONCLUSION: Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL. PMID- 8487047 TI - Unrelated-donor bone marrow transplantation for Philadelphia chromosome-positive chronic myelogenous leukemia in children. AB - PURPOSE: Bone marrow transplantation (BMT) for Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) results in a 55% to 64% disease-free survival (DFS) rate in 20% to 30% of cases with a matched-sibling donor (MSD). Studies that include primarily adults with CML, using unrelated-donor (URD) BMT, have expanded this option to those without an MSD. We review and compare the efficacy of URD and MSD BMT in children with Ph1 CML. PATIENTS AND METHODS: Eleven children with URD BMTs were reviewed and compared with 11 children with MSD BMTs for Ph1 CML. Among the URD BMT recipients, there were three with fully matched marrows and 10 with advanced CML. The median time from diagnosis to transplant was 2.6 years. Among the MSD BMT recipients, 11 had fully matched marrows and five had advanced CML. The median time from diagnosis to BMT was 0.7 years. All received non-T-depleted marrows after cyclophosphamide and fractionated total-body irradiation. RESULTS: Both groups had similar engraftment times. Late graft failure occurred in two URD patients. Graft-versus-host disease (GVHD), > or = grade II, was similar in both groups (77% for URD BMT, 45% for MSD BMT), although more severe acute disease and more persistent chronic disease was seen in the URD group. The Kaplan-Meier estimate of DFS was 45% +/- 15% (SE) and 78% +/- 14% (SE) in the URD and MSD groups, respectively, at 3 years. All had Karnofsky scores of more than 70%, except one URD patient debilitated from GVHD. CONCLUSION: CML is eventually fatal to all patients without BMT. The high survival rate seen among children who receive a URD BMT, despite several adverse factors, opens this important therapeutic option to those without an MSD. PMID- 8487049 TI - Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. AB - PURPOSE: This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs. PATIENTS AND METHODS: Twenty three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity. RESULTS: Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin associated. CONCLUSION: Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs. PMID- 8487048 TI - Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study. AB - PURPOSE: The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS: With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS: The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION: TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL. PMID- 8487050 TI - Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02. AB - PURPOSE: The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS ineligible. PATIENTS AND METHODS: From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm. RESULTS: Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18 month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047). CONCLUSION: SRS eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS. PMID- 8487051 TI - The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer. AB - PURPOSE: The purpose of this study was to develop and validate an instrument for clinical trials to measure radiation-related acute morbidity and quality of life from the perspective of patients with head and neck cancer (HNC) treated with radiotherapy. METHODS: The Head and Neck Radiotherapy Questionnaire (HNRQ) was developed by a panel of health care workers and patients, was pretested in a pilot study of HNC patients, and was validated in a randomized double-blind trial of concomitant fluorouracil (FUra) infusional therapy (1.2 g/m2 per 24 hours) or saline placebo administered for 72 hours in the first and third weeks of a 6 1/2 week course of radiation therapy. The HNRQ was validated against existing toxicity and performance status indices, all of which were measured weekly for the 6 1/2 weeks of treatment and for 4 weeks posttreatment. RESULTS: There were three a priori constructs: (1) that the HNRQ scores would conform to a shallow U shaped pattern to reflect declining quality of life (increasing morbidity) during radiation and recovery posttreatment; (2) that the HNRQ would correlate with existing toxicity indices (World Health Organization [WHO] stomatitis, Byfield stomatitis, WHO skin toxicity, Eastern Cooperative Oncology Group [ECOG] and Karnofsky performance status); and (3) that the HNRQ would discriminate between FUra and placebo groups. The HNRQ and its domain scores all showed a change from baseline reflecting increased morbidity during radiation (analysis of variance [ANOVA], P < .00001). The HNRQ correlated well with all other indices (r > or = .60), and domain scores correlated best with other indices that assess the same symptom complex (eg, HNRQ skin domain and WHO skin toxicity index, r = .77). There was a significant difference in HNRQ scores between the FUra and placebo groups during radiation (ANOVA, P = .0007), and all HNRQ domains also discriminated between the treatment groups. CONCLUSION: The HNRQ is a valid measure of acute morbidity due to radiation therapy in patients with locally advanced HNC, and may be useful as an outcome measure for future clinical trials of radiation treatment strategies. PMID- 8487052 TI - Prognostic value of PS2 and cathepsin D in 710 human primary breast tumors: multivariate analysis. AB - PURPOSE: Evaluation of the prognostic value of cytosolic PS2 (pS2 protein) and cathepsin D in a large series of breast cancer patients by multivariate analysis taking into account steroid receptors and conventional prognostic factors. PATIENTS AND METHODS: Prognostic factors were analyzed in 710 primary breast cancers (median follow-up, 4 years). PS2 and cathepsin D were measured by radiometric immunoassays. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assays and multiple-point Scatchard analysis. RESULTS: The best cutoff point for PS2 to discriminate between positive (61% of the tumors) and negative was 2 ng/mg protein (univariate P value in 5 year relapse-free survival = .003). For cathepsin D, no sensible cutoff point could be chosen, since there was a continuous association between the level of cathepsin D and relapse rate (P = .001). In Cox multivariate analysis, relapse rate decreased with age of premenopausal/perimenopausal patients and with PS2 or steroid receptor positivity, and increased with the size of the tumor, the number of positive lymph nodes, and increasing levels of cathepsin D. In analysis for overall survival, age of both premenopausal/perimenopausal and postmenopausal patients, tumor size, the number of positive lymph nodes, ER/PgR, and PS2 were all independently associated with the rate of death. The level of cathepsin D was positively correlated with the rate of death, but this trend was not statistically significant. Separate Cox multivariate analyses for relapse-free survival in subgroups of patients as defined by nodal status showed that the contribution of PS2 and cathepsin D was the strongest in the node-negative subgroup. Node-negative patients with tumors containing PS2 values < or = 2 ng/mg protein and cathepsin D values more than 70 pmol/mg protein experienced a 4.5 fold increase in relapse rate as compared with those with PS2 levels greater than 2 ng/mg protein and cathepsin D levels < or = 30 pmol/mg protein. CONCLUSION: PS2 and cathepsin D are independent prognostic factors in primary breast cancer and lymph node-negative patients. PMID- 8487053 TI - Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group. AB - PURPOSE: A phase II study was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with metastatic colorectal cancer. PATIENTS AND METHODS: From December 1989 to March 1991, 67 patients with metastatic colorectal cancer were enrolled in this study. Sixty-three patients were assessable for toxicity and response. Their median age was 57 years (range, 24 to 72). Forty-six patients (73%) had a good performance status of 0 or 1. Fifty-one patients (81%) had received prior chemotherapy. The major sites of metastasis were liver (63%) and lung (44%). CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion, or as 150 mg/m2 every 2 weeks. The dose was reduced based on the grade of leukopenia and diarrhea, if necessary. RESULTS: A partial response was obtained in 17 of 63 assessable patients (27%; 95% confidence interval, 16% to 38%). The response rate in patients with prior radiotherapy or chemotherapy was 25% (13 of 52). Liver metastases showed a 15% (six of 40) response and lung metastases showed a 39% (11 of 28) response. The median duration of partial response was 127 days (range, 49 to 353) and the median overall duration of response was 208 days (range, 99 to 381). The major toxicities (> or = grade 3) were leukopenia (16%), diarrhea (13%), nausea and vomiting (13%), and alopecia (11%). Adverse effects were generally well tolerated and reversible. Treatment could be continued on an outpatient basis for patients without severe toxicity. Hemorrhagic cystitis was not encountered in this study. CONCLUSION: CPT-11 showed promising antitumor activity against metastatic colorectal cancer that was resistant to prior therapy. Further clinical trials of combination chemotherapy using CPT-11 are justified. PMID- 8487054 TI - Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenstrom's macroglobulinemia. AB - PURPOSE: To determine the natural history of amyloidosis associated with Waldenstrom's macroglobulinemia and immunoglobulin M (IgM) monoclonal gammopathy. PATIENTS AND METHODS: From January 1968 to September 1990, 50 patients with a serum IgM monoclonal protein and biopsy-proven amyloidosis were evaluated at the Mayo Clinic. There were 32 men and 18 women (age range, 43 to 93 years). RESULTS: Percentages of patients presenting with cardiac, renal, hepatic, and pulmonary amyloid were 44%, 32%, 14%, and 10%, respectively. Forty-two percent of the patients had an M protein value greater than 1.5 g/dL, and 12% had an M component greater than 3 g/dL. Subcutaneous fat, rectum, and bone marrow showed amyloid in 84%, 72%, and 50%, respectively, providing a simple technique for diagnosing amyloidosis. The bone marrow biopsy was consistent with Waldenstrom's macroglobulinemia in 10, a plasma-cell proliferative disorder in 10, and lymphoma or a lymphoproliferative disorder in 11; results were normal, nondiagnostic, or hypercellular in 17. Forty-three of 50 patients died. The median survival of the entire group was 24.6 months. Fifty-three percent of deaths were due to cardiac amyloid, 12% to respiratory failure, 7% to macroglobulinemia, 7% to liver failure, and 7% to kidney failure. CONCLUSION: The presence of amyloid cardiomyopathy and an increased creatinine concentration at diagnosis had an adverse impact on survival. Of the 22 patients who presented with cardiomyopathy, the median survival was 11.1 months, with only two surviving longer than 5 years. The median survival of the 28 patients without cardiomyopathy at diagnosis was 27 months, with eight 5-year survivors (P = .013). All eight amyloid deposits studied stained for Ig light chain, indicating that this amyloidosis is of the primary (AL) type. PMID- 8487055 TI - Interleukin-2-induced thyroid dysfunction is correlated with treatment duration but not with tumor response. AB - PURPOSE: To analyze the putative relationship between immunotherapy-associated dysthyroidism and the probability of a tumor response. PATIENTS AND METHODS: A total of 89 consecutive patients with advanced cancer were treated with interleukin-2 (IL2)-based immunotherapy in a prospective study. RESULTS: Twenty patients developed thyroid dysfunction. Repeatedly positive tests for thyroid antibodies developed in 28% of the patients. Twenty-two patients achieved a response. There was no relationship between the formation of antibodies and the probability of response. There appeared to be a trend toward a relationship between thyroid dysfunction and response (P = .23). A strong relationship was found between response on the one hand and cumulative dose of IL2 (P = .01) and treatment duration with IL2 (P = .025) on the other. The frequency of thyroid dysfunction was also significantly correlated with treatment duration (P = .001). After adjustment for cumulative dose of IL2 and treatment duration, no relationship between thyroid dysfunction and response remained (P = .99). CONCLUSION: There is no relationship between thyroid dysfunction and the probability of tumor response. Thyroid dysfunction is merely a function of treatment duration and cumulative dose of IL2. PMID- 8487056 TI - Splenectomy and the increasing risk of secondary acute leukemia in Hodgkin's disease. AB - PURPOSE: Following irradiation alone, secondary acute nonlymphocytic leukemia (ANLL) is uncommon; following chemotherapy alone, the risk is increased, but not as much as when combined modality treatments are used. Because ANLL seems more likely to occur in splenectomized patients, attention is focused on an unexpected association between splenectomy and the risk of secondary leukemia. PATIENTS AND METHODS: The risk of ANLL was assessed in 503 patients with Hodgkin's disease (HD) homogeneously treated with combined modality therapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP] plus radiotherapy). These patients were diagnosed from 1970 through 1984 and monitored until June 1991. RESULTS: ANLL was observed in one of 145 (0.69%) patients not splenectomized and in 21 of 358 (5.86%) splenectomized patients, demonstrating a significantly higher frequency of ANLL in the group of patients who underwent splenectomy. The group of patients who developed ANLL received a statistically greater number of MOPP courses than did the group not developing ANLL. ANLL was statistically more frequent in those patients who received more than four cycles of MOPP. Sex, symptoms, extent of radiotherapy, splenectomy, age, and number of MOPP courses were assessed for their impact on ANLL incidence by multivariate analysis. CONCLUSION: Cox's proportional hazards regression showed that splenectomy and, as previously described by others, the number of courses of MOPP are prognostic factors that increase the risk of secondary ANLL in HD patients treated with combined modality therapy. These data raise interesting questions regarding the possible role of the spleen in leukemia development. PMID- 8487057 TI - Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study. AB - PURPOSE: Using high-dose therapy and autologous bone marrow transplantation (ABMT) to overcome cellular resistance and eradicate minimal disease, we initiated a pilot study during first remission in patients with non-Hodgkin's lymphoma (NHL) to examine whether the long-term disease-free survival (DFS) rate can be improved for patients with poor-prognosis intermediate/high-grade NHL. PATIENTS AND METHODS: Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved-cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. RESULTS: Following ABMT, no acute in hospital treatment deaths occurred, and engraftment of granulocytes and platelets was significantly faster than for patients undergoing ABMT who were in second or subsequent remission. Of 26 patients, 21 remain in CR maintained without continued therapy, three relapsed in sites of prior nodal disease (4.8, 5.4, and 28 months post-ABMT), and two died in remission. The DFS rate is estimated to be 85% at 28 months and thereafter. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. CONCLUSION: This pilot study suggests that consolidation of first remission with ABMT may improve the long term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse. PMID- 8487058 TI - Phase I evaluation of all-trans-retinoic acid in adults with solid tumors. AB - PURPOSE: Prompted by recent demonstrations that all-trans-retinoic acid (all trans-RA) had efficacy in acute promyelocytic leukemia, a phase I trial of all trans-RA was conducted to establish the maximum-tolerated dose (MTD) before phase II testing. PATIENTS AND METHODS: Forty patients with a histologic or cytologic diagnosis of malignancy other than leukemia were treated with single daily oral doses of all-trans-RA ranging from 45 mg/m2 to 200 mg/m2. Doses of all-trans-RA were escalated in the next cohort of patients until the MTD was determined if the preceding dose level was not associated with significant toxicity. RESULTS: Lung cancer was the most common type of tumor included in the study (26 cases) followed by head and neck squamous cell carcinomas (three cases), and squamous cell carcinoma of the skin (two cases); other miscellaneous solid tumors were also represented. Toxicities included cheilitis, skin reactions, headache, and nausea and vomiting, as well as transient elevations of liver enzymes and triglyceride levels. Skin toxicities, consisting of erythema with desquamation and paronychia, were considered to be the dose-limiting toxicity, and were observed in two of six patients who received 175 mg/m2/d, and in two of five patients who received 200 mg/m2/d. Of the 30 patients with assessable lesions, response was evaluated in 26 patients and no major objective tumor response was observed. Two patients were able to receive the drug for longer than 1 year without significant toxicities. There was considerable variation in individual patients' peak plasma all-trans-RA levels, and a decrease in the area under the curve of all-trans-RA plasma concentration was observed in all four patients evaluated. CONCLUSION: For phase II study of adult patients, we recommend 150 mg/m2 of all-trans-RA administered orally once a day. However, for better optimization of drug administration schedules, further studies are needed. PMID- 8487059 TI - Placebo-blinded study of morphine sulfate sustained-release tablets and immediate release morphine sulfate solution in outpatients with chronic pain due to advanced cancer. AB - PURPOSE: This study was conducted to compare the relative analgesic efficacy and safety of an every-4-hour immediate-release oral morphine (IRM) solution with that of an every-12-hour sustained-release oral morphine (SRM) formulation. PATIENTS AND METHODS: This was a double-blind, placebo-blinded, crossover study in 34 adult male and female outpatients with pain due to advanced cancer. Baseline data were collected on day 1. On days 2 and 3, randomly assigned patients received either placebo plus IRM (Roxanol; Roxane Laboratories, Inc, Columbus, OH; 20 mg/mL) at 2, 6, and 10 am, and 2, 6, and 10 pm, or alternatively SRM (Oramorph SR; Roxane Laboratories, Inc; 30 mg) at 10 AM and 10 PM. Patients were then crossed over to the alternate treatment for days 4 through 6. Pain relief was measured using a conventional 100-mm visual analog scale (VAS) and by recording the incidence of breakthrough pain. Information on side effects was obtained from VAS scores for sedation, nausea, anxiety, and depression; by directly questioning the patient as to mental confusion, bowel movements, and laxative use; and from Karnofsky performance status scores. VAS data were analyzed using a linear statistical model. Breakthrough pain data were analyzed using analysis of variance (ANOVA). RESULTS: There were no statistically significant differences between IRM and SRM treatments with respect to VAS pain scores, side effect scores, or incidence of breakthrough pain data. Karnofsky performance scores remained stable for all patients throughout the study. CONCLUSION: It was concluded that every-12-hour administration of SRM and every-4 hour administration of IRM provide similar analgesic effectiveness and side effect profiles in the treatment of chronic pain in cancer patients. PMID- 8487060 TI - Dose-ranging study of oxycodone for chronic pain in advanced cancer. AB - PURPOSE AND METHODS: We assessed the analgesic efficacy and safety of single entity oxycodone solution at doses greater than 10 mg orally every 4 hours in 24 patients with chronic cancer pain not controlled by weaker analgesics. RESULTS: Twenty of 24 patients completed the study. Pain relief was obtained with doses up to 60 mg every 4 hours. When oxycodone was taken for long periods, further dose increments could be made safely. The side effects of oxycodone are mild, and common to all opioids, with sedation and constipation most frequent. Nausea was more common in females in all age groups and in patients of either sex less than 50 years of age. Episodes of serious toxicity were rare, and responded to dose reduction. Patients older than 65 years required lower doses, suggesting pharmacokinetic similarities between oxycodone and morphine. Patients changed from oral oxycodone to morphine remained pain-free when relative milligram potency ratios of 1:1 to oral morphine and 3:1 to intravenous morphine were used. CONCLUSION: Oxycodone has been shown for the first time to be as versatile and flexible as oral morphine in the management of chronic pain in patients with advanced cancer. PMID- 8487061 TI - Psychosocial outcomes of cancer: a comparative analysis of Hodgkin's disease and testicular cancer. AB - PURPOSE: The psychosocial outcomes of testicular cancer and Hodgkin's disease were compared to test our hypotheses that more specific dysfunction and less hiding of symptoms would be found in the former group, as cancer visibly affects a sexual organ. Since those with Hodgkin's disease could more easily deny the disease, poorer psychosocial adjustment was predicted. PATIENTS AND METHODS: The sample consists of 85 men with Hodgkin's disease and 88 men with testicular cancer (seminomatous, n = 39; or nonseminomatous, n = 49). They were interviewed once, at least 1 year following the end of treatment. Measures of sociodemographic characteristics, physical functioning, psychologic distress, and social outcomes were collected. Treatment data were collected from medical records. RESULTS: Men with testicular cancer report more focused symptoms: less sexual enjoyment and poor health habits. Men with Hodgkin's disease report more generalized symptoms: fatigue, energy loss, and work impairment. Multivariate analysis indicates that most of these differences are site-related; independent effects of treatment on outcomes were found for more generalized symptoms. Contrary to expectations, both groups reported similar levels of infertility and erectile dysfunction. CONCLUSION: The response to testicular cancer is site specific, while the response to Hodgkin's disease is related to both site and treatment (stage-related). PMID- 8487062 TI - Cancer by another name: a randomized trial of the effects of euphemism and uncertainty in communicating with cancer patients. AB - PURPOSE: In this study we tested some assumptions about the use of euphemism in communicating with cancer patients. Does an explicit statement about the diagnosis of cancer cause patients to respond with greater anxiety than when uncertainty or ambiguity is allowed to persist? Do patients believe they cope better with cancer when the diagnosis is explicit? METHODS: A heterogeneous sample of 165 cancer patients completed a new measure of emotional adjustment to cancer using random assignment among four testing variables: agent (self-report v interview), terminology (the words cancer v illness), identification (patient identified v anonymous), and supervision (clinic v home). Internal consistency (Cronbach's alpha) for the 39-item set was 0.74 and face and content validity were determined using the focus-group technique and preliminary factor analysis. After answering the adjustment measures, subjects completed the Spielberger State Trait Anxiety Inventory (STAI). RESULTS: Overall anxiety levels were significantly lower in the sample than published norms for general medical and surgical patients. Exposure to the word cancer as distinct from illness increased anxiety, but did not alter adjustment scores. Supervision and agent conditions did not affect anxiety, but reported adjustment was poorer in the interview condition compared with the self-report condition. Ambiguous instructions, such as asking patients to complete the questionnaire anonymously but return it in person to staff in the clinic, resulted in poorer adjustment, which was reversed by the consistent instruction to complete the questionnaire anonymously at home and return it by mail. CONCLUSION: Use of the word cancer generated anxiety to levels similar to those reported in general medical and surgical patients, but did not produce any distortion in reported adjustment. However, any ambiguity associated with the conditions under which adjustment is assessed may lead to distortion and an increase in the patient's reported psychologic distress. PMID- 8487063 TI - Assessment of sleep in patients with lung cancer and breast cancer. AB - PURPOSE AND METHODS: We studied the sleep architecture and psychologic state of 32 patients with breast or lung cancer compared with 32 age- and sex-matched, normal-sleeping volunteers and 32 otherwise healthy insomniacs. RESULTS: Research findings indicate that lung cancer patients slept as poorly as did insomniacs, but underreported their sleep difficulties. Breast cancer patients slept similarly to normal-sleeping volunteers. No psychiatric disorders were detected in the cancer patients, and there were no significant differences in mood between lung and breast cancer patients. CONCLUSION: Lung cancer patients appear to be unique in underestimating an objectively verified sleep difficulty. The adaptive mechanism of denial in these patients is discussed. PMID- 8487064 TI - Direct thrombosis of aneurysms. PMID- 8487065 TI - The myth of eloquent cortex, or what is non-eloquent cortex? PMID- 8487066 TI - The long-term outcome after surgical treatment of dorsally exophytic brain-stem gliomas. AB - Dorsally exophytic brain-stem gliomas represent a distinctive subgroup of pediatric brain-stem neoplasms that are amenable to radical excision because of their benign histology and growth characteristics. However, their attachment to the floor of the fourth ventricle invariably precludes complete tumor excision. The long-term behavior of the residual tumor remains a subject of concern. To address this issue, the authors reviewed their experience with 18 dorsally exophytic brain-stem gliomas treated between 1974 and 1990. At operation, the tumors filled the fourth ventricle, fungating out of a broad-based area of the dorsal brain stem. The exophytic tumor was resected, but no attempt was made to remove tumor from the brain stem. Histological examination showed that 16 of the tumors were grade I or II astrocytomas, one was a ganglioglioma, and one was an otherwise benign-appearing glioma with several foci of anaplasia that was classified as a grade III astrocytoma. The latter patient was one of only two in the series to receive postoperative radiation therapy; both cases so treated have no evidence of disease on follow-up imaging studies 61 and 135 months postoperatively. One other child who had stable disease postoperatively died of shunt malfunction 18 months after tumor excision. Serial radiographic studies in the other 15 patients have shown no evidence of disease in three, stable residual disease in eight, and tumor enlargement 12, 28, 40, and 84 months postoperatively in four (median follow-up period 113 months). Each of the four patients with tumor regrowth underwent repeat tumor excision. Two of these children received perioperative radiation therapy at the time of disease progression and both showed reduction in tumor volume 28 and 65 months after their second operation. In contrast, both patients who did not receive radiotherapy at the time of disease progression had further tumor enlargement 48 and 84 months after their second operation and underwent a third tumor resection; one received postoperative radiation therapy and has no evidence of disease 58 months after his third operation and the other child has stable disease 27 months postoperatively. Histological examination of tumor specimens obtained at second and third operations showed no change from the appearance of the tumor on the initial resection. The authors conclude that the majority of dorsally exophytic brain-stem gliomas can be managed successfully with subtotal excision and, if necessary, cerebrospinal fluid diversion. The small percentage of tumors in this series that showed recurrent growth remained benign histologically.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487067 TI - Preservation of hearing in surgery for acoustic neuromas. AB - Preservation of hearing was attempted in 161 cases of histologically confirmed acoustic neuroma removed by the senior author between January 1, 1970, and September 30, 1991. There were 136 patients with unilateral tumors; 22 patients had bilateral tumors (neurofibromatosis 2) and underwent a total of 25 procedures. Hearing was initially preserved in 35% of patients with unilateral tumors and in 44% of those with bilateral tumors. Results are reported in terms of pre- and postoperative pure tone average and speech discrimination scores. Surgical access to the tumor was obtained via middle cranial fossa and suboccipital approaches. The latter has been used more often over the past 5 years because of a lower associated incidence of transient facial paresis. Persistent postoperative headaches have been the most common complication following the suboccipital approach. The results of preoperative brain-stem auditory evoked response (BAER) studies were useful in predicting the outcome of hearing preservation attempts. Patients with intact BAER waveform morphology and normal or delayed latencies had a higher probability of hearing preservation in comparison to those with abnormal preoperative BAER morphology. PMID- 8487068 TI - Neurological complications of ankylosing spondylitis. AB - Thirty-three patients with ankylosing spondylitis with or without spinal neurological symptoms requiring surgical intervention were identified in a retrospective review of all cases of spinal disorders treated at the Mayo Clinic during the period from 1984 to 1989. Spinal fractures (traumatic or pseudoarthroses), progressive spinal deformity, rotary instability secondary to atlanto-occipital or atlantoaxial subluxation, and spinal stenosis with associated neurological deficit, pain, or spinal instability were the most common indications for surgery. Of the 41 operations performed, there were 17 cervical, 14 thoracic, and 10 lumbar procedures. Eight patients had two or more disorders at separate spinal levels that required surgery. Preoperative neurological deficits were recorded in 13 patients; these improved following surgery in nine and stabilized in four. This review emphasizes the fragility of the ankylosed spinal column and its inherent susceptibility to fracture with attendant neurological compromise. It also identifies the variety of spinal disorders observed in these patients and discusses their surgical management. The experience with this series suggests that thorough radiological evaluation, extreme caution with endotracheal intubation and with halo-vest applications, early surgical spinal immobilization, and aggressive postoperative mobilization of patients are necessary for a successful outcome. It is concluded that outcomes in these patients can be favorable when managed appropriately. PMID- 8487069 TI - Pulsatile increases in aneurysm size determined by cine phase-contrast MR angiography. AB - The internal flow dynamics were assessed in 16 cerebral aneurysms by cine phase contrast magnetic resonance (MR) angiography. Six of the aneurysms were associated with subarachnoid hemorrhage and 10 were unruptured. The ruptured aneurysms demonstrated a 51% +/- 10% increase in volume between systole and diastole, while the increase in volume of the unruptured aneurysms was 17.6% +/- 8.9% (p < 0.005). The ruptured aneurysms demonstrated an approximate 1.0- to 1.5 mm increase in diameter in at least one dimension during systole. There was no relationship between aneurysm size and volumetric increases. These findings suggest that cine phase-contrast MR angiography can detect structural weakness in the aneurysmal wall. Imaging techniques that can evaluate aneurysmal wall dynamics may be useful in therapeutic planning. PMID- 8487070 TI - Computer-derived density spectral array in detection of mild analog electroencephalographic ischemic pattern changes during carotid endarterectomy. AB - The purpose of this prospective study was twofold: 1) to determine the sensitivity and specificity of computer-derived density spectral array in detecting analog electroencephalographic (EEG) ischemic pattern changes during carotid artery cross-clamping in patients undergoing carotid endarterectomy; and 2) to assess the ability of density spectral array to identify such changes in comparison with the degree and type of change seen in the analog EEG ischemic pattern. Sixteen channels of anteroposterior bipolar and two to four channels of referential electroencephalography with four channels of density spectral array were monitored simultaneously during carotid endarterectomy in 103 patients under general anesthesia. Two "observers" interpreted the density spectral array and the analog electroencephalograms, one during and immediately after the operations and the other 6 months after completion of all surgery. Analyses were conducted to establish both the number of patients with analog EEG ischemic changes and the number of ischemia events during carotid artery cross-clamping. Observer A indicated that the density spectral array identified analog EEG ischemic changes in 21 of 29 patients, for a sensitivity of 72% (specificity 99%), whereas Observer B's results showed that the density spectral array identified analog EEG ischemic changes in 16 of 27 patients, for a sensitivity of 59% (specificity 96%). Density spectral array detection of analog EEG ischemic changes based on severity classifications were 61% and 18% in the mild group, 70% and 71% in the moderate group, and 95% in the severe group, indicating a relationship between density spectral array sensitivity and severity of analog EEG ischemic change, with p = 0.02 and p = 0.004 for the two observers. The kappa statistics for observer reproducibility were highly significant, with k = 0.95 for analog EEG ischemic changes and 0.85 for density spectral array changes. It is concluded that density spectral array does not reliably detect mild analog EEG pattern changes of cerebral ischemia and is not a reliable substitute for 16-channel analog EEG monitoring of cerebral ischemia during carotid endarterectomy. PMID- 8487071 TI - Intraoperative electrocorticography during tumor resection: impact on seizure outcome in patients with gangliogliomas. AB - Gangliogliomas are indolent neoplasms that are often associated with long standing intractable seizures. The seizure-free outcome following ganglioglioma resection alone (or "lesionectomy") has been generally favorable, ranging in most series from 50% to 65%. Thus, the value of resection of epileptogenic cortex in addition to tumor with regard to seizure outcome has been the subject of controversy. The authors describe a series of 12 patients with frontal or temporal lobe gangliogliomas associated with long-standing intractable seizures. In these patients, intraoperative electrocorticography was used to guide the resection of epileptogenic cortex along with tumor. Functional brain mapping, interictal and ictal monitoring of seizures, as well as thorough neuropsychological assessments were performed prior to resection in all cases. Outcome with regard to seizures, tumor recurrence, and neurological deficits was assessed with a mean follow-up period of 3.1 years. There was universal freedom from seizures postoperatively in 11 patients in whom complete or near-complete resection of epileptogenic cortex was achieved. In one patient in whom complete tumor resection and subtotal removal of epileptogenic cortex was achieved, a 95% reduction in seizure frequency was identified. No tumor recurrence or neurological deficits were observed. In a subset of four patients, neuropsychological and cognitive function were evaluated pre- and postoperatively. In these four, a clear trend toward improvement was noted in most functions. Thus, resection of epileptogenic cortex along with tumor may improve seizure outcome in selected patients with tumor-associated epilepsy without engendering identifiable neurological or cognitive deficits attributable to the incremental resection. PMID- 8487072 TI - Radiosurgical treatment of recurrent hemangiopericytomas of the meninges: preliminary results. AB - Hemangiopericytomas of the meninges, classified previously as angioblastic meningiomas, have a propensity to recur either locally or at distant sites within the nervous system after surgical resection. Visceral metastases also develop much more commonly in these lesions than in other types of histologically benign meningiomas. The radiosurgical gamma knife was used to treat five patients with 11 meningeal hemangiopericytomas (seven new, two recurrent, and two residual tumors) after surgical resection of an initially solitary intracranial lesion. Three patients had undergone multiple craniotomies and radiation therapy before referral, and two patients underwent a second radiosurgical procedure for lesions that appeared between 5 and 13 months after the first treatment session. Dramatic tumor shrinkage occurred in most patients within 6 to 10 months after treatment. The only treatment-related morbidity in this series was a partial visual-field defect in one patient with a large falx-tentorial junction hemangiopericytoma who had previously undergone radiation therapy. Radiosurgery appears to cause dramatic early shrinkage of small and medium-sized intracranial hemangiopericytomas that have recurred or developed after previous surgery and/or radiation therapy. PMID- 8487073 TI - A randomized trial of radiotherapy versus radiotherapy plus CCNU for incompletely resected low-grade gliomas: a Southwest Oncology Group study. AB - Sixty adult patients with incompletely excised low-grade gliomas were randomly assigned to receive radiotherapy (55 Gy over a total of 6 1/2 to 7 weeks) either alone or with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 100 mg/sq m every 6 weeks). Pathological review showed that six patients were ineligible for the study. Evaluation of patient age, extent of surgery, tumor grade, and performance status showed no significant differences between the treatment arms. The response rate, as judged by the disappearance or reduction in size of the tumor on computerized tomography scans, was 79% for radiation therapy alone versus 54% for irradiation plus CCNU. The median survival time was 4.45 years for all patients, with no significant difference between treatment arms (p = 0.7). For the group as a whole, patient age and performance status were the most important prognostic parameters. The majority of patients receiving chemotherapy experienced moderate hematological toxicity. This study demonstrates that CCNU chemotherapy does not improve the results of radiation therapy in the treatment of incompletely excised low-grade gliomas. PMID- 8487074 TI - Altered cerebrovascular CO2 reactivity following subarachnoid hemorrhage in cats. AB - The authors tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 was blunted following subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was produced in five cats by performing four cisterna magna injections of blood in each (SAH Group). A second group of six cats was treated with an antifibrinolytic agent (AF) in addition to four cisterna magna blood injections (SAH+AF Group). Four cats received AF and four cisterna magna injections of saline (Control Group). The presence or absence of basilar artery vasospasm was determined by comparing baseline and follow-up selective angiograms. Cerebral blood flow reactivity was determined by randomly varying the concentration of inspired CO2 to alter PaCO2 from 20 to 75 mm Hg. Regional CBF was measured with radiolabeled microspheres. Basilar artery vasospasm was seen following subarachnoid injection of blood but not of saline. Normocapnic CBF was similar in all three groups in the brain stem (mean +/- standard error of the mean: SAH Group 46 +/- 6, SAH+AF Group 46 +/- 6, and Control Group 44 +/- 9 ml/min/100 gm) and in the supratentorial compartment (SAH Group 53 +/- 8, SAH+AF Group 61 +/- 9, and Control Group 51 +/- 13 ml/min/100 gm). At intermediate levels of hypercarbia (PaCO2 50 +/- 3 mm Hg), CBF increased similarly in all three groups (SAH Group 161% +/- 32%, SAH+AF Group 118% +/- 33%, and Control Group 174% +/- 19% compared to baseline); at higher levels of PaCO2 (60 +/- 3 mm Hg), CBF values were SAH Group 265% +/- 50%, SAH+AF Group 205% +/- 47%, and Control Group 159% +/- 30% of baseline. At the highest level of PaCO2 (75 +/- 6 mm Hg), supratentorial CBF did not increase as much in the SAH+AF Group as in the Control Group (179% +/- 59% vs. 463% +/- 58% of baseline, respectively). The authors conclude that, in this model of SAH, there is no change in normocapnic CBF; however, blood flow reactivity to hypercarbia is blunted. It is possible that this may result from a combination of narrowing of proximal large vessels and globally impaired reactivity of small vessels. PMID- 8487075 TI - Cardiovascular responses to global cerebral ischemia: role of excitatory amino acids in the ventrolateral medullary pressor area. AB - The object of this study was to investigate the role of the ventrolateral medullary pressor area in mediating the cardiovascular responses to experimentally induced global cerebral ischemia, and to test if excitatory amino acids or acetylcholine are the transmitters released in this brain region during these responses. The cerebral ischemic response was elicited in pentobarbital anesthetized, artificially ventilated male Wistar rats by bilateral ligation of vertebral arteries followed by temporary clamping of the common carotid arteries. The pressor area was identified by microinjections of L-glutamate. Inhibition of neurons in this area by microinjections of muscimol, a gamma-aminobutyric acid receptor agonist, abolished the ischemic response, which demonstrated that this area is important in mediating these responses. Microinjections of a broad spectrum excitatory amino acid receptor blocker (kynurenate), of specific antagonists for N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors (injected alone or in combination), and of atropine failed to block the ischemic responses. These results indicate that: 1) the ventrolateral medullary pressor area mediates pressor responses to cerebral ischemia, and 2) excitatory amino acids or acetylcholine in this area do not mediate the cardiovascular responses to cerebral ischemia. PMID- 8487076 TI - Epileptogenic effect of antibiotic drugs. AB - The epileptogenicity of antibiotic drugs represents a clinical problem, and it is well known that the use of penicillin and certain other preparations can induce seizures. In the present study, the authors investigated the epileptogenic properties of different concentrations of 12 commonly used antibiotic medications belonging to seven separate groups. The drugs were tested in the hippocampus, which has a low threshold for the development of epileptiform activity. The hippocampal slice technique, using rat tissue, was employed since absence of the blood-brain barrier allows administration of the drugs in known concentrations. The preparation was exposed to antibiotics in known concentrations and the amplitude and number of population spikes were recorded. Penicillin G was used as a reference substance. Cloxacillin (> or = 1 gm/liter), cephalothin (> or = 1 gm/liter), gentamicin (> or = 80 mg/liter), chloramphenicol (> or = 1 gm/liter), ciprofloxacin (> or = 50 mg/liter), erythromycin (> or = 1 gm/liter), and ampicillin (> or = 1 gm/liter) showed moderate to marked epileptogenic effects, whereas cefuroxime, clindamycin, cefotaxime, vancomycin, and tobramycin had no epileptogenic effects. PMID- 8487077 TI - The effect of transforming growth factor-beta 2-specific phosphorothioate-anti sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma. AB - This in vitro study was aimed at restitution of transforming growth factor (TGF) beta 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-1 alpha and interleukin-2 in vitro (lymphokine-activated killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-beta could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-beta neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-beta 2-specific S-ODN's resulted in decreased TGF-beta-specific immunoreactivity in cultured glioma cells, in reduced TGF-beta 2 protein concentration (Western blot), and in a change in the expression pattern of TGF beta 2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells. PMID- 8487078 TI - Effect of recombinant tumor necrosis factor-alpha on three-dimensional growth, morphology, and invasiveness of human glioblastoma cells in vitro. AB - In order to investigate the antiproliferative and anti-invasive effects of tumor necrosis factor (TNF)-alpha on human glioblastoma cells, an in vitro three dimensional (anchorage-independent) assay was performed using Matrigel, a mixture of extracellular matrix proteins. Four glioblastoma-derived cell lines, including one cloned line, were cultured in Matrigel with or without TNF-alpha. In the Matrigel containing TNF-alpha, three of the four cell lines, including the cloned line, showed significant growth inhibition in a dose-dependent manner. Dramatic three-dimensional morphological differences were observed between TNF-treated and untreated glioblastoma cells cultured in Matrigel. Untreated cells formed large and highly branched colonies throughout the gel. In contrast, the majority of TNF treated cells demonstrated truncated branching processes and, at a high TNF-alpha dose, an increasing number of cells remained in relatively small spherical aggregates, their cell processes being significantly reduced. Quantitative invasion assay using a micro-Boyden chamber system confirmed that TNF-treated cells lost invasiveness in a dose-dependent manner. These results suggest that TNF-alpha exerts not only antiproliferative but also anti-invasive effects on human glioblastoma cells in vitro. It is believed that this is the first report showing the anti-invasive effect of TNF-alpha on tumor cells. PMID- 8487079 TI - A brain-tumor model utilizing stereotactic implantation of a permanent cannula. AB - A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-microliters injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-microliter injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acid protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/- standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-microliters volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure. PMID- 8487080 TI - Myelomeningocele and thick filum terminale with tethered cord appearing as a human tail. Case report. AB - Tail-like caudal appendages may be associated with spinal dysraphism, particularly with spinal lipomas or lipomyelomeningoceles. An unusual case is presented of a patient with a myelomeningocele and a thick filum terminale with tethered spinal cord, which presented with the external appearance of a human tail. A review of the literature reveals that human tails may be associated with dysraphic conditions. Extensive neuroradiological examinations should be performed for all such cases of apparent tails. PMID- 8487081 TI - Transcallosal interforniceal approach for a posteriorly projecting high basilar bifurcation aneurysm. Case report. AB - A transcallosal interforniceal approach was used for treatment of a posteriorly projecting high basilar bifurcation aneurysm with a neck located 30 mm above the posterior clinoid process. The aneurysm was successfully clipped via the third ventricle with minimal neurological deficits. This approach appears to be appropriate for basilar bifurcation aneurysms located more than 20 mm above the posterior clinoid process when the fundus projects posteriorly, and permits direct visualization of the aneurysmal neck and vital perforators with minimal brain retraction. PMID- 8487082 TI - Giant serpentine middle cerebral artery aneurysm treated by extracranial intracranial bypass. Case report. AB - Giant intracranial aneurysms often pose difficult management issues. Such aneurysms may not be amenable to direct surgical attack because of their size, location, or lack of a clear aneurysmal neck. In such cases, a combination of strategies may provide a means of proximal aneurysm occlusion and distal cerebral revascularization. The authors report the successful treatment of a giant (186.8 ml) serpentine aneurysm of the left middle cerebral artery (MCA) in a 14-year-old boy. The aneurysm was managed in a two-stage procedure in which the MCA branches distal to the aneurysm were anastomosed first with branches of the left superficial temporal artery. After the bypass procedure, direct occlusion of the MCA was performed at the proximal base of the aneurysm at its site of dilatation. The patient had no intraoperative or postoperative complications and was intact neurologically 6 months following the procedures. PMID- 8487083 TI - Optic nerve ganglioglioma. Case report. AB - Gangliogliomas of the optic nerve are extremely rare. The case is reported of a 38-year-old man who presented with a visual field deficit and was discovered to have an optic nerve ganglioglioma. The possible embryological origins of this neoplasm, its histological and immunohistochemical features, and its appearance on magnetic resonance imaging are examined. The prognoses of optic nerve glioma and of gangliogliomas occurring elsewhere in the nervous system are compared. PMID- 8487084 TI - Superficial temporal artery interposition graft after resection of bilateral anterior cerebral arteries. Case report. AB - A patient with an olfactory neuroblastoma in the frontal skull base was treated with primary tumor excision and partial resection of the A2 segment of both anterior cerebral arteries (ACA's). Revascularization was carried out using a superficial temporal artery (STA) interposition graft between the proximal and distal stumps with A3 segment-to-A3 segment end-to-side anastomosis. This technique established flow to the peripheral territories of the ACA's through the interposed STA graft. The technical aspects and possible role of this procedure are presented. PMID- 8487085 TI - A study of safe entry zones via the floor of the fourth ventricle for brain-stem lesions. Report of three cases. AB - Direct surgery for intra-axial lesions of the brain stem is considered a hazardous procedure, and morbidity of varying degrees cannot be avoided even with partial removal or biopsy. The main causes of morbidity relate to direct damage during removal of the lesion, selection of an entry route into the brain stem, and the direction of brain stem retraction. The authors examined the possibility of making a medullary incision and retracting the brain stem, taking into account the symptomatology and surgical anatomy, and found two safe entry zones into the brain stem through a suboccipital approach via the floor of the fourth ventricle. These safe entry zones are areas where important neural structures are less prominent. One is the "suprafacial triangle," which is bordered medially by the medial longitudinal fascicle, caudally by the facial nerve (which runs in the brain-stem parenchyma), and laterally by the cerebellar peduncle. The second is the "infrafacial triangle," which is bordered medially by the medial longitudinal fascicle, caudally by the striae medullares, and laterally by the facial nerve. In order to minimize the retraction-related damage to important brain-stem structures, the brain stem should be retracted either laterally or rostrally in the suprafacial triangle approach and only laterally in the infrafacial triangle approach. Three localized intra-axial brain-stem lesions were treated surgically via the safe entry zones using the suprafacial approach in two and the infrafacial approach in one. The cases are described and the approaches delineated. Both approaches are indicated for focal intra-axial lesions located unilaterally and dorsal to the medial lemniscus in the lower midbrain to the pons. Magnetic resonance imaging is useful in selecting these approaches, and intraoperative ultrasonography is helpful to confirm the exact location of a lesion before a medullary incision is made. These approaches can also be used as routes for aspiration of brain-stem hemorrhage as well as for tumor biopsy. PMID- 8487086 TI - Biopsy-proven isolated sarcoid meningitis. Case report. AB - Neurosarcoidosis without systemic involvement is rare and difficult to diagnose. The case of a 27-year-old man with a 6-week history of headache, mental status changes, and polyradiculopathy attributable to hypoglycorrheic lymphocytic meningitis is presented. Extensive testing for occult systemic sarcoidosis was negative. The presence of noncaseating granulomatous inflammation was established by open brain biopsy, and the patient improved clinically with oral steroid therapy. In individuals with undiagnosed chronic meningitis, brain biopsy may be necessary to rule out isolated neurosarcoidosis. PMID- 8487087 TI - Systemic T-cell lymphoma presenting with isolated neurological dysfunction and intraparenchymal brain lesions. Case report. AB - Secondary non-Hodgkin's lymphoma of the central nervous system is typically a late manifestation of systemic T-cell lymphoma, with a 2-month median survival time after the development of neurological disease. Of the reported patients with this late complication, only 1% manifest spread of the disease to the brain parenchyma. The authors report a patient with an unusual initial neurological presentation of systemic T-cell lymphoproliferative disorder and associated space occupying lesions of the brain parenchyma. The diagnosis was supported by extensive molecular, immunological, and histopathological analysis. Neurological symptoms appeared early in the course of systemic disease and were characterized by spontaneous exacerbations and remissions. The patient has survived for more than 5 years since the onset of his neurological symptoms. Histopathological characterization including immunoperoxidase staining for T-cell markers, DNA content, and cell-cycle analysis of brain tissue obtained at stereotactic biopsy were compared to those of atypical lymphoid cells of peripheral blood, bone marrow, and liver. The neurological manifestations and possible etiologies of T cell lymphoma are discussed. PMID- 8487088 TI - Mary Shaw Shorb (1907-1990) PMID- 8487089 TI - Nutrient bioavailability, with special reference to calcium. AB - The term "bioavailability" attempts to include in a single concept the effect of a sequence of metabolic events, i.e., digestibility, solubilization, absorption, organ uptake and release, enzymatic transformation, secretion and excretion. Each of these events is difficult to measure experimentally, and, with the possible exception of digestibility and solubilization, all are age-dependent and subject to nutritional and hormonal controls. In the case of calcium, the body's demand increases and then decreases with age; it also increases with pregnancy and lactation. Age, pregnancy and lactation each affect the regulatable component of the intestinal absorption of calcium. The passive component of calcium absorption is a function of the amount of calcium solubilized and of intestinal transit time. Inasmuch as digestibility and solubilization of calcium are very difficult to determine separately, even a reliable measure of calcium absorption includes a measure of uncertainty. If one wishes to include in the term "calcium bioavailability" rates of net deposition in bone, as well as rates of excretion from the body, quantitative information on calcium pool size, turnover and the effects thereon of age, sex, endocrine and nutritional status are needed. In the case of other nutrients, rates of enzymatic transformation and organ utilization need also to be taken into account. It will therefore require major research programs before the term "bioavailability" of a nutrient can become a quantitative concept useful for clinical, nutritional or managerial evaluation and counseling. PMID- 8487090 TI - Degree of protein deficiency affects the extent of the depression of the antioxidative enzyme activities and the enhancement of tissue lipid peroxidation in rats. AB - To investigate the effects of various dietary protein levels on tissue lipid peroxidation and antioxidative enzyme activities, four groups of Long-Evans male weanling rats were fed a 6, 8, 12 or 20% lactalbumin diet for 6 wk. The red blood cell in vitro spontaneous hemolysis values were 28.6, 24.9, 18.9 and 14.1% for the rats fed the 6, 8, 12 and 20% lactalbumin diets, respectively. The thiobarbituric acid-reactive substances (TBARS) in plasma, RBC, liver, kidney, muscle, lung, spleen and heart were lowest in the group fed the 20% lactalbumin diet. Rats fed the diet containing 12% lactalbumin had significantly greater TBARS in plasma, spleen, kidney and muscle compared with rats fed the 20% lactalbumin diet. Rats fed the 8% lactalbumin diet had markedly higher TBARS levels (P < 0.05) in all tissues examined than did those fed the 12% lactalbumin diet. The TBARS in all eight tissues of the rats fed the 6% lactalbumin diet were even higher than those of rats fed the 8% lactalbumin diet (P < 0.05). The activities of glutathione peroxidase, superoxide dismutase and glucose-6 phosphate dehydrogenase in RBC were gradually lowered (P < 0.05) when the dietary protein level was decreased stepwise. The activities of these antioxidative enzymes in liver also were reduced significantly when dietary protein level decreased from 20 to 12% and then to 8%. These enzyme activities in the rats fed the diet containing 6% lactalbumin generally were not different from those of the rats fed 8% lactalbumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487091 TI - Perinatal food restriction in rats reduces the content but not concentration of liver extracellular matrix proteins. AB - Fibrosis of the liver has been reported to be associated with malnutrition, based on qualitative histological and histochemical approaches. The aim of this study was to quantitatively examine the effect of perinatal food-restriction on the expression of extracellular matrix components of the liver, using rats fed 50% of ad libitum intake, determined by the food consumption of the control group on the previous day. Levels of extracellular matrix proteins were measured by dot blot analysis using monospecific antibodies against collagen types I, III and IV, laminin and fibronectin. The body weights of 4, 8 and 13-wk-old malnourished groups were 25, 35 and 48% of the control group body weights, respectively, and the liver weights were 22, 32 and 60% of the controls. The total contents of the extracellular matrix components were significantly reduced to 30, 34 and 58% of the controls, but when expressed per tissue or per milligram protein there were no significant differences. Indirect immunofluorescence revealed no major changes in extracellular matrix localization. The major histological change in the food restricted rats was fatty infiltration. Our observations suggest that the effect of perinatal food restriction is mainly liver steatosis, and that the liver of food-restricted animals during the perinatal period has the capacity to preserve its main extracellular matrix components. PMID- 8487092 TI - Metallothionein gene is expressed in developing rat intestine and is induced by zinc but not by corticosteroids. AB - The expression of metallothionein (MT) mRNA during perinatal development of rat intestine and its induction by zinc and corticosteroids were studied. Pregnant rats from d 17 to 22 of gestation and rats at 2, 4, 13 and 21 d of postnatal life were injected with saline solution (control) or with zinc (10 mg/kg body wt) or corticosteroids (1 mg/kg body wt). After 6 h, tissues were removed for analysis. Northern hybridization of polyA + RNA to 32P-MT-cDNA revealed that MT was expressed already at d 17 of fetal life, increased afterwards (reaching the maximal expression around birth) and decreased soon after until weaning. Metallothionein mRNA was markedly induced by zinc at d 18 of fetal life to a level that remained constant throughout postnatal life. Corticosteroids were ineffective in inducing MT gene expression during prenatal and postnatal development. In 21-d-old adrenalectomized rats the level of MT mRNA was similar to that of control rats of the same age and was not changed by hormone treatment. The results indicate that MT gene expression can be induced by zinc during fetal life and that its expression without exogenous inducers cannot be ascribed to circulating corticosteroids. PMID- 8487093 TI - Vitamin A deficiency impairs some aspects of the host response to influenza A virus infection in BALB/c mice. AB - We examined the impact of vitamin A deficiency on the host response to an acute, viral infection of the respiratory tract by infecting BALB/c mice with a mouse adapted strain of influenza A virus. Several indicators of the severity of infection were examined, including the rate of virus clearance from the lungs, the extent of inflammatory lesions, and percentage of survival. None of these was affected by vitamin A deficiency. Following the acute phase of infection, however, the regeneration of normal, respiratory epithelium was impaired and adenomatoid, metaplastic lesions developed within inflammatory foci in the lungs of deficient animals. The antibody response to infection was also characterized: the influenza A-specific immunoglobulin A (IgA) response in the respiratory tract was markedly decreased by vitamin A deficiency, but tracheal and lung lavage IgG titers were not affected. The serum IgM and IgG responses, and the serum hemagglutination-inhibition response, were also diminished by vitamin A deficiency. Decreased mucosal IgA titers and impaired regeneration of normal respiratory epithelium could impair recovery from a primary infection and increase susceptibility to opportunistic secondary infections. PMID- 8487094 TI - Vitamin E status does not affect the responses to exercise training and acute exercise in female rats. AB - Responses of vitamin E-depleted female rats to acute exercise and chronic exercise training were tested. Rats were fed either a control diet (+E rats) or a vitamin E-depleted diet (-E rats). After 8 wk, subgroups of the +E and -E rats performed treadmill exercise for 45 min at 28 m/min, 15% grade, and were immediately killed. Vitamin E concentrations were 80-90% lower in liver, heart and muscles in -E rats as determined by HPLC. There was no difference between +E and -E rats in blood lactate concentration, creatine kinase, lipid peroxidation indices, hematocrit or hemoglobin concentration following acute exercise. Remaining rats were either trained for a further 8 wk at 40 m/min, 15% incline for up to 60 min/d or served as untrained controls. No differences in training tolerance were seen between diet groups, with 64% of +E rats and 71% of -E rats consistently completing 60 min of daily training. The training induced similar adaptive elevations in succinate dehydrogenase activity (31-107%) in various hind limb muscles of both +E and -E rats. Trained +E rats had lower vitamin E concentrations in some but not all tissues when compared with untrained +E controls. These results suggest that consumption of a vitamin E-free diet for 8 wk did not result in differences in blood indices associated with exercise stress or in the ability to perform a submaximal acute exercise test when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487095 TI - Household and preschooler vitamin A consumption in southwestern Kenya. AB - This study examined the effects of an income-generating policy to expand the commercialization of subsistence agriculture in southwestern Kenya on household and preschooler macro- and micronutrient consumption. A representative sample of 617 household was included, and all preschoolers under the age of 6 y (1677) residing in these households were included in the study. Results of this analysis indicate that although increases in household income do result in improved household level vitamin A consumption, increases in household income are not significantly associated with the intake of dietary vitamin A by preschoolers. The analysis suggests that although increases in household income have some very positive effects on household food security and household micronutrient consumption, other community-based health, sanitation and nutrition interventions are needed to address the dietary needs of individuals within the household. PMID- 8487096 TI - Human serum concentrations of all-trans beta- and alpha-carotene but not 9-cis beta-carotene increase upon ingestion of a natural isomer mixture obtained from Dunaliella salina (Betatene). AB - The uptake of all-trans and 9-cis beta-carotene and of alpha-carotene from a natural carotene preparation from Dunaliella salina, Betatene, was studied in humans. All-trans beta-carotene and alpha-carotene were absorbed well and showed the expected biokinetics with serum peak concentrations between 24 and 48 h. The mean increase in serum concentrations of alpha-carotene was 5.6% of the increase of all-trans beta-carotene, reflecting the composition of these carotenoids in Betatene. 9-cis beta-Carotene, however, was not detected in human serum, even after repeated doses. This could be due to preferential absorption of all-trans beta-carotene, rapid distribution of 9-cis beta-carotene into the tissue, or the presence of isomerase activity processing 9-cis to all-trans beta-carotene. PMID- 8487097 TI - Rat liver is not damaged by high dose tryptophan treatment. AB - Adult male Sprague-Dawley rats were treated with USP-grade L-tryptophan at a level of 250 mg/kg seven times over 14 d or three times over 3 d by gastric gavage. At autopsy liver specimens were prepared for histological study by stains specific for lipids, for glycoprotein and glycogen, and for fine structure by electron microscopy. Liver lipid did not accumulate as a result of tryptophan treatment. In a series of unfed animals, however, liver lipid had accumulated within 24 h of food withdrawal. Tryptophan has been implicated in fatty liver development by several reports that cite each other, but, in all cases but one, unfed animals were used, and the data show that liver lipid was already present in the unfed animals at the beginning of the experiment. Tryptophan has also been cited as causing abnormal liver morphology, but our evidence suggests that such observations are the result of artifact induced by frozen section preparation and not the result of tryptophan treatment. Our experiments indicate that tryptophan administered to rats at dosages in excess of those recommended for humans does not induce fatty liver or other morphological changes detectable by the methods described. PMID- 8487098 TI - Biological efficacy of copper in chicken bile. AB - Newly hatched chicks were fed a Cu-deficient casein-soybean concentrate diet (0.56 mg Cu/kg) during an 8-d pretest period, after which they were fed experimental diets containing graded levels of added Cu from CuSO4.5H2O during a 15-d assay period. Following the Cu-depletion period, gall bladder Cu concentration decreased from 645 nmol/g dry matter at hatching to 60 nmol/g dry matter at d 8 posthatching; liver Cu concentration decreased during the same period from 255 to 225 nmol/g dry matter. During the subsequent 15-d repletion period, a sevenfold linear increase in gall bladder Cu occurred as Cu was supplemented up to 2 mg Cu/kg, after which it declined gradually in birds fed graded doses between 2 and 16 mg Cu/kg. Liver Cu also increased linearly as Cu was supplemented up to 2 mg/kg; when chicks were fed between 2 and 16 mg/kg of supplemental Cu, liver Cu concentration remained constant. Bile obtained from chicks fed 800 mg Cu/kg diet for 22 d was freeze-dried, analyzed and found to contain 3.05 mumol Cu/g dry matter. When 8-d-old Cu-depleted chicks were fed graded levels of supplemental Cu (0, 0.5 and 1.0 mg Cu/kg) from CuSO4.5H2O, bile Cu concentration increased linearly from 10.5 to 102.7 mumol/L. Bile Cu did not increase when freeze-dried bile (1.0 mg Cu/kg diet) was supplemented. When 0.5 mg Cu/kg from CuSO4.5H2O was supplemented in combination with 0.5 mg Cu/kg from freeze-dried bile, bile Cu concentration was less than one-half the level present in chicks fed 0.5 mg Cu/kg from CuSO4.5H2O alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487099 TI - Nutrient oxidation by rat intestinal epithelial cells is concentration dependent. AB - The kinetics of oxidative metabolism of glucose, glutamine, acetate and butyrate were determined in cells isolated from the jejunum and colon of young, fed rats. Jejunal and colonic cells were isolated from the same animal and incubated with a single radiolabeled substrate at concentrations ranging from 0.005 to 25 mmol/L, and 14CO2 production was determined. Carbon dioxide production was concentration dependent and saturable for all substrates. Data points within the range of the apparent half-maximal oxidation rate were transformed by use of a Lineweaver-Burk plot to calculate K(ox), the concentration at which there was half-maximal oxidation, and Vmax, the calculated maximal rate of oxidation. In jejunal cells, the K(ox) for glucose and glutamine were 0.40 and 0.45 mmol/L, respectively. The K(ox) for glucose, glutamine and acetate ranged from 0.80 to 0.88 mmol/L in colonocytes, whereas the K(ox) for butyrate was 0.33 mmol/L. Except for butyrate in colonocytes, the observed maximal rate of oxidation was comparable to the calculated maximal rate. The substrate concentration required to ensure that substrate was not limiting for its oxidation was estimated at 5 mmol/L for glucose and glutamine in enterocytes and colonocytes, 5 mmol/L for acetate in colonocytes, and 0.50 mmol/L for butyrate in colonocytes. This study showed that attention needs to be given to the concentration of substrate used for in vitro studies. PMID- 8487100 TI - Total parenteral nutrition containing medium- vs. long-chain triglyceride emulsions elevates plasma cholesterol concentrations in rats. AB - Male Fischer 344 rats (235-246 g) were fed for 6-14 d by intravenous or intragastric infusion with total parenteral nutrition (TPN) solutions providing 40 or 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. In three separate experiments, plasma cholesterol concentrations were significantly greater (24 32%) with intravenous infusion of TPN solutions containing MCT-LCT rather than LCT. Plasma cholesterol concentrations in rats were not significantly different with intragastric infusion of TPN solutions containing MCT-LCT rather than LCT. Hepatic total lipid and triglyceride concentrations were not significantly different. Hepatic total cholesterol and esterified cholesterol concentrations were significantly lower in animals given 65% of energy from MCT-LCT rather than LCT emulsions (main effects, two-way ANOVA). The concentration of individual hepatic acyl-CoA esters reflected the fatty acid profiles of the lipid emulsions infused. Total hepatic acyl-CoA concentrations suggested differences in utilization of acyl-CoA esters with intravenous infusion of MCT-LCT rather than LCT and were consistent with rapid oxidation of MCT. These data demonstrate that MCT-LCT elevates plasma cholesterol concentrations compared with LCT emulsions with intravenous, but not with intragastric, infusion of TPN solutions in rats. PMID- 8487101 TI - Growth is compromised in rats fed ozone-treated casein. AB - Modified casein containing few phenylalanine residues and no other aromatic amino acid residues was obtained by ozonolysis of casein. Although 68% of phenylalanine was decomposed by ozonolysis of casein, ozonolysis caused alterations beyond the destruction of aromatic amino acid residues. Nearly the same degree of decomposition of amino acid residues was observed in casein ozonated after predigestion by pepsin. Rats were fed diets containing 8% casein supplemented with methionine and aspartic acid (8C-AA), 8% ozonated casein supplemented with methionine and free amino acids lost by ozonolysis (8OC-AA), 8% casein ozonated after predigestion by pepsin supplemented with methionine and free amino acids lost during preparation (8POC-AA) or 7.6% amino acid mixture. The growth of rats fed the 8OC-AA diet was significantly lower than that of those fed 8C-AA or 7.6AA diets. The growth of rats fed the 8POC-AA diet was comparable to growth of those fed 8OC-AA. The biological values of the 8OC-AA and 8POC-AA were comparable to that of 8C-AA, but true digestibility of 8OC-AA was significantly lower than that of 8C-AA. True digestibility 8POC-AA was significantly improved relative to 8OC AA, but the growth of rats fed 8POC-AA was not improved relative to that of those fed 8OC-AA. Kidney and cecum weights of rats fed 8OC-AA and 8POC-AA were significantly heavier than those of the 8C-AA-fed group, although histopathological examination of kidneys showed no deterioration compared to that of the 8C-AA-fed group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487102 TI - Hydrolysis of proline dipeptides completely fulfills the proline requirement in a proline-auxotrophic Chinese hamster ovary cell line. AB - Proline- and hydroxyproline-containing oligopeptides may be important in protein nutrition because intestinal hydrolases are incapable of recognizing their imido bonds. Peripheral tissues have a cytosolic enzyme prolidase that cleaves dipeptides containing C-terminal proline (X-Pro) or hydroxyproline. The role of dipeptides in intracellular metabolism is uncertain. This study examined the ability of X-Pro to provide proline to the proline-auxotrophic cell line, CHO-K1. The action of prolidase on exogenously supplied Gly-Pro, the most abundant dipeptide product of digestion, provided adequate proline to support normal cell growth of CHO-K1 cells in a dose-dependent manner. The growth curve generated by addition of Gly-Pro to CHO-K1 cells was similar to that due to proline. Two other structurally unrelated X-Pro also supported growth indistinguishably from Gly Pro. Gly-Hyp was completely ineffective for growth. The ability of X-Pro to sustain cultures of a proline-auxotrophic cell line may be important in elucidating intracellular nutritional and physiological functions for those dipeptides. PMID- 8487103 TI - Riboflavin requirement of healthy elderly humans and its relationship to macronutrient composition of the diet. AB - The riboflavin requirements of two groups of riboflavin-deficient, but otherwise healthy, Guatemalan elderly persons over the age of 60 y were studied by varying the fat:carbohydrate ratio in two diets. The first group consumed a diet similar in macronutrient content to a Western-type diet with low carbohydrate and high fat; the second group consumed a typical Guatemalan diet with high carbohydrate and low fat. Energy and protein intakes of both groups were similar. Riboflavin status was monitored by weekly measurements of erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Increasing increments of riboflavin were added to the subjects' diets until their status was normalized, as indicated by EGRAC of < 1.34 and a sharp increase in urinary riboflavin excretion. Using the EGRAC method, the mean value of riboflavin intake at which the subjects' EGRAC reached the limit of normality was 1.37 +/- 0.03 mg/d in the first phase and 1.29 +/- 0.03 mg/d in the second phase. The sharp increase in urinary excretion occurred at riboflavin intakes of 1.13 and 1.03 mg/d for Groups 1 and 2, respectively. Thus, the differences between the two groups suggest that diets with a lower fat:carbohydrate ratio can decrease the dietary need for riboflavin. The dietary requirement of riboflavin, as estimated by the more reliable urinary excretion method, was 1.1-1.3 mg/d for those consuming the Western-type diet, which is similar to values found over 40 y ago in young adults. We conclude that the dietary requirements of riboflavin in the elderly do not differ from those of young adults. PMID- 8487104 TI - Liver vitamin A levels in rats are predicted by a modified isotope dilution technique. AB - We tested the hypothesis that the fraction of an injected dose (FDp) of [3H]retinol remaining in plasma could be used to predict liver vitamin A mass. Rats (n = 36) with liver vitamin A ranging from 1.4 to 23,000 nmol received an intravenous dose of [3H]retinol-labeled plasma. Plasma samples obtained at 4, 4.4, 5, 5.4, 6, 7 and 8 d were analyzed for radioactivity; liver vitamin A levels were determined at 8 d. Using a regression equation developed previously [liver vitamin A (nmol) = 7493.exp(-148.FDp)], there was a log linear relationship between FDp and liver vitamin A mass from 1.4 to 5200 nmol retinol; the equation did not predict levels > or = 7500 nmol. By expanding the regression equation [liver vitamin A (nmol) = 88,928.exp(-1347.FDp) + 5606.exp(-120.FDp)] and using the FDp at 4.4 d, liver vitamin A levels ranging from < 4 to 23,000 nmol were well predicted. Satisfactory equations were also developed for data obtained at 4, 5 and 5.4 d. We conclude that this modified isotope dilution technique is a sensitive and reliable method for assessing vitamin A status in rats over a wide range of vitamin A nutriture. It is likely that this method could be modified for use in humans. PMID- 8487105 TI - Gastric acid production, iron status and dietary phytate alter enhancement by meat of iron absorption in rats. AB - This study was designed to determine whether gastric acidity, added phytate or iron status significantly influenced the effects that dietary proteins have on iron absorption. Rats were fed test meals of wheat cereal, with and without an added dietary protein (beef, pork, chicken, fish or egg white), by gavage. The influences of phytate and gastric acid were investigated by adding sodium phytate to the test meals and by treating the rats with cimetidine to inhibit gastric acid production. Iron status was altered by dietary regimens. Significant (P < 0.05) effects of the proteins were determined by comparison of the various protein-containing meals to control meals of cereal or cereal + phytate, as appropriate. Gastric acidity, phytate and iron status were all confirmed as factors significantly affecting iron absorption. Beef, pork and chicken enhanced iron absorption, but only when phytate had been added to the meals and only in iron-deficient rats. Enhancement by meat was sufficient to overcome the inhibition by phytate. Fish was an inhibitor or enhancer in cimetidine-treated, iron-deficient rats, depending on the absence or presence of phytate, respectively. Egg white inhibited absorption from cereal meals in cimetidine treated, iron-deficient rats. PMID- 8487106 TI - Amino acid compositions of body and milk protein change during the suckling period in rats. AB - The amino acid concentrations of rat body protein and rat milk protein were measured at 1, 6, 10 and 16 d of age to determine whether the concentration of each amino acid in proportion to the concentration of total recovered amino acids (amino acid composition) in the body changes during early growth and development and whether parallel changes occur in the amino acid composition of milk. The ratio of essential to nonessential amino acids in bodies decreased 10% during the suckling period (P < 0.05). The ratio of essential to nonessential amino acids in milk proteins decreased by 6% (P < 0.05). With the exception of threonine, the body to milk ratio for each essential amino acid seemed similar to that for the other essential amino acids, implying that most essential amino acids are equally limiting for the synthesis of body protein in exclusively milk-fed pups. Measurements of milk intake and milk composition were used to determine amino acid intakes and hence the efficiency with which milk amino acids were used for body protein deposition. The efficiency of essential amino acid utilization was 75% between 1 and 6 d, 86% between 6 and 10 d, and 62% between 10 and 16 d of age. Although the overall efficiency of nonessential amino acid utilization showed a similar pattern, the results suggested the need for a high degree of glycine and arginine synthesis. PMID- 8487107 TI - The form of response of body protein accretion to dietary amino acid supply. AB - The mean response of body protein accretion in growing animals to their amino acid intake is sometimes described by a rectilinear ("broken-line") model and sometimes by a curvilinear model. The response of a population may be curvilinear as a result of averaging individual rectilinear responses or because individual responses are themselves curvilinear. This experiment was undertaken to distinguish these possibilities by examining the responses of individual animals. Eighteen pigs with a mean initial weight of 35 kg and a mean final weight of 73 kg were each fed, in a different sequence, six diets providing a daily nitrogen intake of 0.5, 1.5, 1.83, 2.17, 2.5 or 3.5 g/kg body wt0.75. Each diet was given for 10 d, with complete collections of feces over the last 6 d and of urine over the last 4 d. Rates of nitrogen retention (expressed per kg0.75 per day) were related to rates of nitrogen intake (in the same units) using a rectilinear (broken line), an exponential or a saturation kinetics model. Mean square errors were significantly larger for the rectilinear model than for either of the curvilinear models and were slightly but not significantly less for the saturation kinetics model than for the exponential model. PMID- 8487108 TI - Determination of nutritional requirements in rats: variation with time of weight gain responses to indispensable amino acids. AB - The Saturation Kinetics Model (SKM) can be used to describe physiological responses as functions of a limiting dietary nutrient. Physiological responses also vary with time, and, by graphing each parameter of the SKM as a function of time, the model equation can be used to produce a three-dimensional response surface, allowing the investigator to predict requirement as a function of both dietary nutrient concentration and time. To test this hypothesis, rats were fed diets containing graded levels of indispensable amino acids (0-10 g/100 g). The inhibition form of the SKM was able to predict the complete response range of weight gain, food intake, weight-specific weight gain and weight-specific food intake for each amino acid on a day-by-day basis. With a complete response range established, nutrient requirements (defined as maximum responses) could be determined explicitly by the equation: Requirement = (K0.5.KS)0.5, where K0.5 and KS are parameters of the SKM. No arbitrary decisions (such as break points, slopes, percentages of maximum, etc.) were necessary to accomplish this. This approach allows one to set nutritional requirements and optimize responses in a dynamic system without causing inhibiting and/or toxic responses. In each case (valine, methionine, threonine and histidine), the dietary amino acid concentration required for maximal weight gain exceeded current NRC recommendations, which may be low because they fall in the more time-dependent portion of the response curve whereas maximum responses do not. PMID- 8487109 TI - Colon and stomach cancer mortality among automotive wood model makers. PMID- 8487110 TI - Board-certified occupational physicians. PMID- 8487111 TI - What is the current treatment of asphalt skin burns? PMID- 8487112 TI - Walking by circular saws used to cut aluminum caused increasing pain at a previous laceration site. Is there a connection between sound energy and increasing wound pain? PMID- 8487113 TI - Laser hazards in research laboratories. AB - Laser use is expanding rapidly in laboratories, where multiple use strategies of research are not often amenable to laser engineering safeguards employed in industry. We report on five cases of laser-associated incidents requiring medical follow-up from a single research institution, and present exposure circumstances from four other incidents. Eye injuries from direct and reflected beams resulted from open alignment procedures in the absence of appropriate eye protection. Nd:YAG lasers operated with doubling crystals appear to create a considerable risk. For several reasons, we believe the importance of laser-associated injuries are underestimated and the incidence underreported in the research setting. Although knowledge personnel are shown to suffer lapses in standard operating procedures, most incidents and all injuries involved relatively inexperienced personnel. We propose that research laser users be registered and required to undergo formal training in laser safety. Student researchers are a key target population. Collaborative implementation between the equipment supplier and research user will be required to achieve this widespread implementation of effective training. PMID- 8487114 TI - N-of-one clinical trials. The practice of environmental and occupational medicine. AB - The randomized clinical trial is the paradigm of causal documentation in clinical medicine. It spawned an extension, the "N-of-one clinical trial," used as diagnostic instrument in the clinical practice of internal medicine to demonstrate the presence or absence of truly beneficial treatment. The author presents an extension of the method to environmental and occupational medicine, provides an example, and discusses the limitations of the approach. A guideline and justification for the provision of such services is suggested. PMID- 8487115 TI - Employment in electronics manufacturing and risk of spontaneous abortion. AB - A large case-control study of environmental risk factors for spontaneous abortion was conducted among women living in Santa Clara County, California. Because of the prevalence of electronics production work within this population, a specialized questionnaire was administered to women who self-identified as electronics production workers. Spontaneous abortions were identified from pathology records, and controls were identified from birth certificates. The odds ratio for spontaneous abortion and any electronics production work was 0.94 (95% confidence interval = 0.58, 1.5). Odds ratios for the three main branches of electronics production (semiconductor fabrication, printed circuit board manufacturing, and assembly) were likewise near or below unity. Specific production activities with elevated odds ratios included semiconductor diffusion, parts encapsulation, soldering, and flux removal, although the numbers were small and none of the confidence intervals excluded unity. Limitations of this study included modest statistical power and a potential for nondifferential misclassification of exposures, both of which could bias findings toward the null. PMID- 8487116 TI - Healthy worker effect in a cross-sectional study of lead workers. AB - To study the role lead may play in the development of renal disease, we performed a cross-sectional study of workers at a lead smelting plant. Renal function was defined based on calculated creatinine clearance using the prevalence of values under the 3rd percentile to compare groups. The prevalence of calculated creatinine clearance values under the 3rd percentile in these workers (n = 1782) as a whole was 2.81%, a result comparable to that which has to be expected for the general population. Closer analysis, however, showed significantly lower prevalence of calculated creatinine clearance under the 3rd percentile in certain subgroups of workers. These subgroups were workers between the ages of 30 and 39, workers over the age of 50, and Belgian workers who had worked in the plant for longer than 10 years. We conclude that these observations once more clearly demonstrate a "healthy worker effect" on the measurement of renal function in this work force, a major problem in epidemiologic cross-sectional studies. PMID- 8487117 TI - Dermatitis in workers exposed to antimony in a melting process. AB - An employee at a brazing rod manufacturing plant developed a generalized eruption of follicular papules and pustules. His job tasks included breaking up antimony ingots and melting the pieces in a crucible; he was exposed to antimony metal dust and to antimony trioxide fumes. Two fellow employees who later performed the same job tasks developed similar eruptions. The clinical and workplace evaluations suggested that the fumes from melting antimony were the cause of the dermatoses, and that the current Occupational Safety and Health Administration permissible exposure limit is not adequate to prevent cutaneous effects of antimony exposure. PMID- 8487118 TI - Multidisciplinary rehabilitation of chronic work-related upper extremity disorders. Long-term effects. AB - The prevalence of work-related upper extremity disorders has significantly increased in the past decade. Persistent pain, loss of function, and associated work disability in patients with work-related upper extremity disorders appears to be affected by multiple factors including physical capabilities in relation to work demands, ergonomic risk factors on the job, and psychological factors related to worker traits, psychological readiness to return to work, and ability to manage symptoms. The complex nature of these disorders suggests the utility of a multidisciplinary program targeted at these factors. The present study is an investigation of the long-term vocational outcome of a multicomponent rehabilitation program that includes physical conditioning, work conditioning, work-related pain and stress management, ergonomic consultation, and vocational counseling/placement. Two groups equivalent on measures of duration of work disability, pain severity, fear of reinjury, psychological distress, perceived work environment, age, and education level were exposed to either the comprehensive work rehabilitation intervention (n = 19) or usual care (n = 15). Return-to-work status was determined at an average of 17 months posttreatment (range, 3 to 35 months) for the treatment group and an average of 18 months postevaluation (range, 5 to 30 months) for the usual care group. Findings indicated that 74% of the treatment group returned to work or were involved in state-supported vocational training in contrast to 40% of the control group (P < .05). For those who returned to work, 91% of the treatment group were working full-time in contrast to 50% of the control group (P < .05). Although the treatment group demonstrated a higher return-to-work rate than controls, the work reentry rate was not as high as similar approaches with work-related low back pain (80% to 88% return-to-work rate). These findings suggest the need to modify treatment components to facilitate an increased return-to-work rate. Areas that may prove useful include a greater emphasis ergonomic modifications at the workplace to reduce the risks of repetitiveness, force, awkward posture, and insufficient work/rest cycles, as well as efforts to modify work style directly in order to reduce the impact of ergonomic stressors on the ability to perform essential job tasks. In combination with traditional work hardening efforts directed at improving strength and flexibility of the upper extremities and work related pain and stress management training, these ergonomic and work-style modification efforts may contribute to increases in the percentage of work disabled cases who successfully return to competitive work. PMID- 8487119 TI - Biochemical indicators of hazardous shoulder-neck loads in light industry. AB - Prolonged, repetitive handling of light material is known to increase the risk of shoulder-neck disorders. Biological risk indicators related to musculoskeletal exposure, applicable by the general practitioner in the workplace, could provide an instrument for early intervention and rehabilitation. Eight women were studied, all full-time workers performing assembly tasks associated with a high prevalence of shoulder-neck complaints. All subjects were more tender in the shoulder region than young women in low-risk occupations. Heart rate recordings indicated a low general metabolic load during work. Concentrations in antecubital venous blood of several markers for metabolic stress and cellular damage (lactate, ammonia, hypoxanthine, urate, malondialdehyde, potassium, creatine kinase) were normal for all subjects, and showed no increase during 3 consecutive working days. Thus, the blood markers did not reflect hazardous shoulder-neck exposure. PMID- 8487121 TI - A cohort mortality study of two California refinery and petrochemical plants. AB - This study examined the 1973 to 1989 mortality experience of Shell's two California manufacturing locations' employees who worked more than 6 months before December 31, 1989 and pensioners who were alive as of January 1, 1973. Vital status of each employee as of December 31, 1989 was determined from various sources including company records, the National Death Index, and the Social Security Administration's Master Beneficiary Record file. The study included many long-term employees, with more than half (57%) of the total population working 20 years or longer. The total population exhibited 11% lower all causes mortality and 20% lower cancer mortality, as compared with the California general population. There were no significant excesses of any cause-specific mortality including cancer. Among total employees, mortality for several cancer sites showed a statistically nonsignificant increase, for example, cancer of the kidney (8 observed deaths and 6.02 expected), cancer of the bladder (11 observed deaths and 9.17 expected), and Hodgkin's disease (2 observed deaths and 1.01 expected). A review of these work histories revealed no predominant work area or job assignment. In contrast to the ecologic studies based on local county rates, lung cancer mortality in this study was significantly lower (Standardized Mortality ratio [SMR] = 0.73). In addition, statistically significant deficits in mortality were found for cirrhosis of the liver (SMR = 0.63) and all external causes of death (SMR = 0.74). This study also failed to show an increased mortality rate for cancers of the brain, stomach, and prostate--causes which have been reported to be elevated in other refinery and petrochemical employee studies. PMID- 8487120 TI - The Canadian Labour Force Ten Percent Sample Study. Cancer mortality among men, 1965-1979. AB - The mortality experience of 415,309 men enrolled in the Canadian Labour Force 10% Sample Study has been updated to the end of 1979. The occupation and industry in which these men were employed between 1965 and 1969 were available, and these records were matched to the Canadian National Mortality Data Base by computerized record linkage. A total of 9,739 deaths from cancer between 1965 and 1979 were identified. Analyses were conducted with respect to men employed in 274 occupations and 294 industries with respect to mortality from 33 different types of cancer resulting in 243 associations in which the 90% lower confidence bound for the relative risk compared to the whole cohort had a value of 1.0 or greater. Based on the criteria of strength of association, dose-response, and consistency, 23 associations were identified as being of particular interest. Of these associations, four (waiters, bartenders and breweries with cancer of the buccal cavity and pharynx, and bartenders with lung cancer) seem most likely to be caused by excess smoking and/or alcohol consumption, and could provide a useful guide for intervention strategies focused on those employed in these occupations. A further seven (carpenters and stomach cancer, clerical occupations and colon cancer, truck drivers, plumbers and pipefitters, sheet metal workers, shipbuilding and repair, and asbestos products manufacturers with lung cancer) have support in terms of biological plausibility and/or other studies in the literature and appear to warrant more intensive study. The third group of associations, although demonstrating strength of association, a dose-response effect, and/or consistency, may well have arisen by chance given the many comparisons made in this study. PMID- 8487122 TI - The effect of self-care brochures on use of medical services. AB - A random sample of 14,917 new enrollees in a state-wide health maintenance organization was selected as part of a study of the effectiveness of medical self care brochures. Medical ICD-9 codes related to each of the conditions described in the brochures were examined for the intervention group (N = 7439) and controls (N = 7478). Significantly less utilization was found for visits due to colds in the month following brochure distribution (P < .01). While not statistically significant, trends in the expected direction of less utilization for earaches and less total medical charges for the intervention group were also found. No significant differences were found related to headache and backache symptoms, although a greater proportion of the intervention group reported backache symptoms. Utilization related to sore throats and fever was significantly (P < .001) higher in the intervention group. These findings suggest that a minimal intervention such as brochure distribution can have a favorable, albeit minimal, impact on medical services utilization. Self-care education may also play a role in increasing utilization for certain types of health conditions. PMID- 8487123 TI - Immunological probing of induction and repair of 8-methoxypsoralen photoadducts in DNA from Fanconi anemia and normal human fibroblasts: quantitative analysis by electron microscopy. AB - A direct method of immuno-electron microscopy has been employed to simultaneously determine 8-methoxypsoralen (8-MOP) photoinduced monoadducts (MA) and interstrand cross-links (CL), their relative localization along the DNA molecule, and their removal. It has been applied to DNA from cultures of Fanconi anemia (FA) fibroblasts (complementation groups A and D), and of normal human fibroblasts, following treatment by 8-MOP and 365 nm radiation. The immuno-reaction with monoclonal antibody 8G1 was performed on DNA extracted from the cells just after photoreaction, or after a 24 h repair period, and then denatured. Furan-side MA and also a significant proportion of pyrone-side MA were very efficiently immuno detected. Only 1-2% CL were IgG-labeled. This is why CL were directly visualized and quantified on denatured DNA from the same cellular samples as used for immuno detection. Results demonstrate that FA group A cells are not only impaired in the incision of CL, but also of MA. The response of FA group D cells is intermediate between normal and FA group A cells. PMID- 8487124 TI - Protein dynamics and fluorescence quenching. AB - There are both theoretical and experimental data which strongly suggest that the intramolecular dynamics of the protein matrix play an important role in protein functions. The interrelationship between theory and experiments is rather weak mainly because of the lack of relevant experimental methods and (model-dependent) misinterpretation of experimental data. We give a short account of a few fluorescence-quenching techniques that can provide adequate information concerning protein dynamics provided that the experimental data sets are correctly processed. PMID- 8487125 TI - Structure-activity relationships for DNA photocleavage by cationic porphyrins. AB - The influence of molecular structure and DNA binding mode on the ability of cationic porphyrins to photosensitize DNA strand break formation has been studied for a series of meso-substituted pyridinium porphyrins using electrophoretic and DNA sequencing techniques. Porphyrins substituted with pyridyl groups in which the heterocyclic nitrogen is in the para or meta position vis-a-vis the substitution point are capable of intercalative binding and are considerably more efficient DNA photosensitizers than the corresponding non-intercalating ortho compounds. Within each group of porphyrins the photosensitizer efficiency increases with the number of positive charges. Using DNA sequencing experiments, we have demonstrated that photomodification occurs primarily at the guanine and thymine bases, and that alkali-labile sites produced by photo-oxidation are as important as direct cleavage events. The kinetics of strand degradation in aerated and degassed solution suggest that type II reactions (probably mediated by singlet oxygen) occur with significantly higher yield than type I reactions and are responsible for the formation of alkali-labile sites in aerated systems. These observations seem to confirm the hypothesis that those structural features which influence the strength and mode of binding also serve to establish favourable porphyrin-DNA interactions for photosensitization. PMID- 8487126 TI - Light-induced photon emission by mammalian cells. AB - In this work, the light-induced photon emission (IPE) by suspensions of mammalian cells was examined. IPE is extremely low and for detection in a single photon counting device with a cooled EMI 9558QB photomultiplier tube was used. The mammalian cells in this study were from different tissues and different mammalian species including cat, Chinese hamster, cow, dog, human, monkey, mouse and rat. The IPE was detected in all mammalian cells tested, but was different for the various cell types, ranging from 4 to 100 photons per 10(4) cells. Although our data agree with previous studies in that the IPE of non-fibroblastic normal cells is distinct from that of malignant cells our results reveal that cells of fibroblastic origin show the highest IPE values. PMID- 8487127 TI - Inactivation and mutation induction to 6-thioguanine resistance in V79 Chinese hamster fibroblasts by 313 nm radiation: some problems of action spectroscopy. PMID- 8487128 TI - Photoreactivation of DNA synthetic activity in human embryo fibroblasts. PMID- 8487129 TI - Flow cytometric analysis of DNA sensitivity to nuclease S1 in UVC-irradiated human fibroblasts. AB - The sensitivity of human fibroblast DNA towards the activity of nuclease S1 was investigated in situ after irradiation of the cells with UVC light. DNA digestion was assessed using flow cytometry by staining the nuclease-resistant DNA fraction with the specific fluorochrome propidium iodide (PI). The results showed a non linear dependence of DNA digestion on the UVC irradiation dose between 0 and 20 J m-2. About 70% of the UVC-induced DNA sensitivity to nuclease S1 was lost after 30 min of repair. These results suggest that flow cytometry may be useful for assessing the heterogeneity of cell response to UV damage. PMID- 8487130 TI - The use of 5-aminolevulinic acid (ALA) in photodynamic therapy (PDT). PMID- 8487131 TI - Toxicity of local anesthetics in infants and children. AB - Local anesthetics are extremely useful for providing anesthesia and analgesia for infants and children of all ages. Despite the toxicity issues raised here, the overall safety record of local anesthetic use in pediatrics has been very good, and local anesthetic administration within safe guidelines should be encouraged. In the great majority of cases, toxic reactions have been associated with either inadvertent intravascular injection or unintentional overdosage by physicians who did not adequately consider issues related to systemic drug uptake, distribution, or clearance. Unlike opioids, which can be titrated according to clinical signs to a wide range of doses, local anesthetic administration must be strictly limited "by the numbers." Pediatricians, surgeons, emergency room physicians, and anesthesiologists need to be informed regarding limits for the administration of local anesthetics and management of toxic reactions. PMID- 8487132 TI - Psychologic perspectives on pediatric pain. AB - Pain has always been a salient feature for children because it occurs frequently in their everyday lives. We are only beginning to understand childhood pain. Yet, it is this understanding that influences our assessment and treatment of their pain. As with adults, pain in children is a complex matrix of biologic, psychologic, and sociologic phenomena. This article reviews what we know today about childhood pain and focuses on the psychologic perspectives that affect that pain experience. It outlines the psychologic elements that include: cognition, coping strategies, ability to communicate pain, fear, temperament, and personality as well as the sociologic factors, such as the family, culture, and economics, that influence children's perceptions and reactions to pain. The article concludes with a review of psychologic treatments of pain and an exploration of the effects of the psychology of adults, including professional anxiety and beliefs about pain and medication, on how pain is experienced by children. PMID- 8487133 TI - Eutectic mixture of local anesthetics (EMLA): what is it? What does it do? PMID- 8487134 TI - Topical anesthesia and pain management before venipuncture. PMID- 8487135 TI - Use of the eutectic mixture of local anesthetics in young children for procedure related pain. PMID- 8487136 TI - The use of topical anesthesia in removal of port-wine stains in children. AB - The control of pain associated with laser treatment of port-wine stains in children has been problematic. Using EMLA, a topical anesthetic, children can be treated with a significant reduction in laser-induced pain. In this prospective, double-blind, placebo-controlled, randomized trial of EMLA, 73 children (35 boys and 38 girls) ranging in age from 5 to 16 years with port-wine stains were treated. EMLA reduced mean pain scores 66% when compared with control subjects (p < 0.0001 for all three assessments of pain). Concordance between evaluators' and patients' assessment of pain scores correlated strongly (p < 0.001). Treatment with EMLA abolished pain in 40% of patients and the percentage of pain-free treatments increased from 10% to 52% (p < 0.001). EMLA is clearly effective in reducing or eliminating pain associated with laser treatment of port-wine stains in children. PMID- 8487137 TI - Needle phobia: an anesthesiologist's perspective. PMID- 8487138 TI - Identifying the best scenario for using schematic organizers as integration tools for alcohol-related information. AB - The goal of the present study was to examine scenarios for using two schematic organizers--schematic knowledge maps and conceptual matrices--in integrating episodic and semantic knowledge about alcohol. Seventy students from undergraduate general psychology classes participated for course credit. Participants were assigned to either a schematic organizer group or an essay writing group. These groups were subdivided further into two treatment sequences: episodic/semantic and semantic/episodic. The episodic activity required participants to complete materials using their own alcohol-related experiences, whereas the semantic activity required participants to annotate expert materials. Assessment measures used were consumer-satisfaction questionnaires and free recall tests. While no preferences were established for any one scenario, the episodic activities were rated higher than the semantic activities regardless of integration sequence. The semantic/episodic integration scenario did produce higher recall scores for the expert information. PMID- 8487139 TI - Gender differences and similarities in patterns of drug use and attitudes of high school students. AB - The purpose of this research was to study the results of a large scale drug survey of high school students in the context of the baseline data provided by four previous surveys. These surveys were conducted at three-year intervals beginning in 1977. The most recent survey contained self report data from 2,000 students representing fifteen schools in northeast Ohio. The instrument yields information on fourteen categories of drugs. Gender differences in drug use, perceived harmfulness of drugs, and age of first experimentation are reported. No gender differences were found in the reasons students give for turning to drugs. Baseline data from the four previous surveys comprised approximately 8,000 respondents. PMID- 8487140 TI - The relationship of cigarette smoking and other substance use among college students. AB - A questionnaire relating to cigarette smoking behavior and use of other substances was administered to 863 college students in the state of Oregon. Results indicated that there was not a significant difference between cigarette smokers and non-smokers with regard to use of smokeless tobacco, alcohol consumption, or marijuana use. There was, however, a significant difference in the use of other illicit substances when comparing cigarette smokers and non smokers. Cigarette smokers were much more likely to use illicit substances on an occasional or regular basis than were non-smokers. Smokeless tobacco users who indicated that they consumed alcohol and used marijuana and other illicit substances were more likely to consume more alcohol on a weekly basis than non users. They were also more likely to use marijuana and other illicit substances on an occasional and regular basis. PMID- 8487141 TI - Drug involvement among potential dropouts and "typical" youth. AB - Drug involvement, conceptualized as drug use frequency, drug access, drug use control, and adverse use consequences, is described and compared among two randomly selected groups of students aged fourteen to nineteen years: 203 low risk typical high-school students and 160 youths at high-risk of school problems and dropout. High-risk youth, compared to low-risk youth and national statistics, endorsed a much greater breadth and depth of drug use, greater access to drugs, less drug use control, and greater adverse consequences due to use. A secondary analysis showed low-risk users (experimenters) were similar to high-risk youth in their access to drugs and eroding drug use control, but showed low frequencies of drug use and negligible adverse use consequences. Measuring and exploring these four facets of drug involvement provided a robust picture of the adolescents' drug milieu and revealed differences in patterns of drug involvement that would not have been evident by looking purely at drug use frequency. Implications for prevention programming are suggested. PMID- 8487142 TI - HIV risk factors among pregnant and non-pregnant high-risk women in New York City. AB - A comparison of high-risk pregnant (n = 55) and non-pregnant (n = 598) women from Harlem, New York City on HIV-related drug and sexual risk behaviors was undertaken to identify appropriate prevention and intervention policy recommendations. Clients were recruited for an AIDS risk reduction research demonstration project and were either intravenous drug users (IVDUs) or sexual partners of IVDUs. There was a higher percentage of IVDUs among the non-pregnant women, and no significant differences were found between pregnant and non pregnant IVDUs in terms of needle risk behaviors. The two groups were also similar in non-injected drug use behaviors. Pregnant women were significantly less likely to use condoms. Recommendations focused on the need for increased HIV risk reduction among high-risk women in general, and increased education efforts among pregnant high-risk women regarding condom use as protection from HIV and the potential consequences of maternal substance use for their children. PMID- 8487143 TI - An outcome evaluation of Here's Looking At You 2000. AB - This study reports outcome evaluation results from a segment of one of the most widely used drug education/prevention programs entitled "Here's Looking At You 2000." HLAY 2000 was offered to the seventh and eighth grade students (n = 463) by regular classroom teachers of Yadkin County Schools located in one of the rural areas in North Carolina. Six schools served as the experimental group while two randomly selected schools served as a control group. The program was implemented during the 1990-91 school year. PMID- 8487144 TI - Teacher ratings of student risk for substance use as a function of specialized training. AB - The purpose of this study was to determine if teachers' abilities to identify accurately students who are at risk for substance abuse can be improved through attendance at a specialized training program. Sixty-three eighth-grade teachers participated in the study. Of these, thirty-six teachers participated in the training sequence (intervention group), while the remaining twenty-seven teachers served as a comparison group. All eighth-grade students in the school district were surveyed regarding their substance usage. Teachers rated the students regarding their risk for substance usage. Teachers' ratings and students' reported substance usage were compared to assess the percentage of matching responses. After training, the intervention teachers provided more accurate ratings among usage categories than did the comparison teachers. The trained teachers were better at correctly identifying the students who were at risk for substance use. PMID- 8487145 TI - Extracurricular activities: are they an effective strategy against drug consumption? AB - This work describes data obtained among 16,117 high-school students in fifteen Brazilian cities, involving participation in a number of extracurricular activities and consumption of drugs and alcohol. In the great majority of cases, no association was found between attendance of artistic-, community-, or sports related activities and the use of these substances. On the other hand, a weak but constant negative association was found involving alcohol/drug consumption and attendance of religious activities. The authors discuss these findings in the light of some current preconceptions prevailing in Brazilian society: namely, that such activities constitute effective strategies for drug use prevention and the "idle" young persons tend to be potential drug users. They also discuss the implications that among students involved in religious activities drug and alcohol consumption was shown to become slightly lower. PMID- 8487146 TI - Hypertension during pregnancy in Africa and infants' health. A cohort study in an urban setting. AB - The objective of the study was to assess the prevalence of unclassified hypertension during pregnancy and its consequences on infant's health in an African urban setting: Pikine, a suburb of Dakar, Senegal. A cross-sectional study of a random sample of pregnant women and a prospective study, from the inclusion to seven days after delivery, were performed. 886 women attending the prenatal centers were included in the cross-sectional study. 471 pregnant women were included in the follow-up study. The prevalence of DBP > or = 120 mmHg was 0.7%; 5.7% of the women had DBP > or = 95 mmHg. Longitudinal data were available for 425 deliveries. Two spontaneous abortions, 25 stillbirths, and 12 deaths during the early neonatal period were recorded. Among babies living at birth, the percentage of LBW (> or = 2500 g) was 8.5%. The percentages of adverse outcome of pregnancy (death and/or low birth weight) was associated with mothers' diastolic BP: < 85 mmHg: 13%; 85 to 89: 16%; 90 to 94: 9%; DBP > or = 95: 32%, (p < 0.01). Using 95 mmHg as a cutpoint, the relative risk of adverse outcome associated with a DBP > or = 95 mmHg was 2.5 (CI 95%: 1.4-4.3). This risk was significantly increased among women who reported difficult living conditions. Eight percent of the adverse outcomes of pregnancy, 10% of the low birth weights and 8% of the perinatal mortality were found to be associated with DBP > or 95 mmHg. PMID- 8487147 TI - Transvaginal color Doppler in the assessment of the uteroplacental circulation in normal early pregnancy. AB - Transvaginal color Doppler investigation of the uteroplacental circulation was performed on 108 pregnant women with normal intrauterine pregnancy. Decline of resistance index (RI) and pulsatility index (PI) and increase of peak systolic velocity (Ps velocity) were found in all segments of the uteroplacental circulation with advancing gestational age. There was a decrease of RI and PI from the uterine artery through its branches: arcuate, radial and spiral arteries. Ps velocities decreased from the uterine, through the arcuate, to the radial arteries, but Ps velocities in the spiral arteries were higher than those in the radial arteries. According to our results RI seems to be more precise in the assessment of the uteroplacental than the PI. PMID- 8487148 TI - Uterine activity in spontaneous labour and maternal peripheral plasma prostaglandin E2 and F2 alpha metabolites. AB - The relationship between maternal peripheral plasma concentrations of prostaglandin E2 and prostaglandin F2 alpha metabolites (bicyclo-PGEM and PGFM respectively) and the level of uterine activity in spontaneous labour was studied in 10 nulliparous and 10 multiparous women. Plasma prostaglandin metabolites were measured by radioimmunoassay. Uterine activity was quantified by computer analysis of changes in intrauterine pressure and expressed as mean active pressure (MAP). As labour progressed, both parity groups showed a significant rise in MAP which was associated with a significant increase in the levels of PGFM. However, the percentage rise in PGFM did not significantly correlate with the percentage rise in MAP. At all stages in labour PGFM and MAP levels were higher in the nulliparous group compared with the multiparous group. Bicyclo-PGEM levels showed no significant change in the nulliparous group but rose in late first stage/second stage in the multiparous group. Our observations support a role for prostaglandin F2 alpha in the generation of uterine activity in spontaneous labour. However, further study is required to elucidate the mechanisms controlling prostaglandin production by the fetal membranes and decidua in vivo, and how this relates to maternal peripheral plasma prostaglandin metabolite concentrations and the level of uterine activity. PMID- 8487149 TI - Staff views on parental visiting of very low birthweight infants in neonatal intensive care units--results of a staff enquiry across eleven countries of the European Community. EC-Study Group on Parental Involvement in Neonatal Intensive Care. AB - As part of a larger European study of parental visiting and involvement in the care of very low birth weight infants in neonatal intensive care units, the results of a self-completed anonymous enquiry of 1008 medical/nursing staff of 35 units in 11 European countries are presented. The study demonstrates a general agreement with parental visiting and involvement, with sometimes striking differences in views of staff of different countries, but with little or no differences between medical and nursing staff. Staff with more than seven years experience in neonatal care have a less positive attitude towards parent's presence in the unit. The same holds true for staff of units that have a restricted policy toward parents' visiting, i.e. units which do not have a 24 hours visiting policy for parents. PMID- 8487150 TI - Water birth--is it safe? AB - Water births have gradually become more popular in industrialized countries during the last decade. People advocating this form of delivery argue that the buoyancy in water helps the mother to relax and that the warmth helps reduce pain, meaning that the whole labor process and experience is positively influenced and even accelerated. Due to the sitting position and lower pressure gradient, there are supposedly fewer injuries to the birth canal, and delivery is also claimed to be easier on the child. However there is a great lack of scientific data. We have found only one publication in a peer reviewed journal with some 100 water births described. In a case controlled study not published the authors found fewer birth canal injuries and less use of analgesics but the difference was only slight. There was no difference in the length of labor. Several neonatal deaths are reported during uncontrolled water births. Based on the knowledge available to date, physiologic and general considerations (e.g. risk of infections, risk of hypoxia, risk of aspiration), water births must be classified as a type of obstetrical management, whereby the risks are still too undetermined to be said to be a safe form of birth. Water births should, thus, be restricted to centers with adequate medical assistance, and only in randomized, controlled studies who fulfill the Declaration of Helsinki. In any other setting water births should be rejected, since too little is known about the safety of this method. PMID- 8487151 TI - Influence of perinatal risk factors on the involution of the irido-pupillary membrane. AB - The aim of this study was to assess the influence of common perinatal risk factors on the disappearance of the anterior vascular capsule of the lens (AVCL). Direct ophthalmologic examinations were performed on 75 neonates (27 to 35 weeks gestational age) in the first 24 hours after birth, using the degree of involution of the AVCL to estimate gestational age in high risk pregnancy. Our results show that the gradual disappearance of the AVCL is not influenced by perinatal risk factors, such as maternal preeclampsia, prenatal administration of steroids, neonatal infection and low birth weight, confirming the clinical value of this test in the assessment of gestational age in high risk babies. PMID- 8487152 TI - Vitamin A status in preterm and term infants at birth. AB - Vitamin A status was determined in infants born at term or prematurely to assess if vitamin A levels at birth were related to gestational age. Vitamin A levels were measured in cord blood samples from 13 infants born at term and in blood samples obtained within two hours of birth in 26 preterm infants (median gestational age 31 weeks, range 27-35). None of the preterm infants developed chronic lung disease. The vitamin A levels of the term infants (median 0.71 mumol/l, range 0.34 to 1.27) were significantly higher than those of infants born preterm (median 0.35 mumol/l, range 0.12 to 1.22), p < 0.01. Vitamin A levels correlated significantly with gestational age (vitamin A level = 0.024 gestational age (weeks) -0.23, r = 0.39, p < 0.02. We thus conclude that gestational age must be taken into account when interpreting vitamin A levels. PMID- 8487153 TI - Antenatal diagnosis and outcome in hydrops fetalis. AB - The records of 15 cases of hydrops fetalis consecutively delivered at our institution were reviewed to determine the accuracy of antenatal diagnosis and whether antenatal diagnostic techniques yielded information useful in predicting outcome. All 15 cases were detected antenatally, five were due to rhesus haemolytic disease and 10 were non-immune hydrops. All the infants required active resuscitation. Ten infants eventually died, two had immune hydrops fetalis and 8 non-immune hydrops. Seven infants had pleural effusions, all had been detected antenatally. The presence of pleural effusions did not influence mortality. All structural abnormalities were accurately detected in those patients seen prior to labour and there were no survivors in the group of infants so affected. We conclude that the mortality of non-immune hydrops fetalis remains high and that antenatal diagnosis of this condition is accurate and provides useful prognostic information. PMID- 8487154 TI - Neonatal adaptation in hypertensive pregnancy--a study of labetalol vs hydralazine treatment. AB - Twenty mothers with moderate to severe preeclampsia were allocated to labetalol (Trandate) or hydralazine (Apresolin) antihypertensive treatment. Arterial blood gas analysis was performed at delivery from the clamped cord. Neonatal blood pressure, heart rate and axillary temperature were registered 0.5, 2, 6, 12, 24, 36, 48 hours and 3, 4 and 7 days after birth. Respiratory rate was registered at the same intervals until 36 hours after birth. Blood glucose levels were measured 2, 6, 12 and 24 hours after birth. Peripheral blood flow in the calf was measured at 24 hours of age. Gestational age did not differ between the two groups; 36 (27 40) in the labetalol, and 35 (29-37) weeks in the hydralazine group (median and range). Median cord pH was lower, and the number of infants with a cord pH < 7.20 was higher in the hydralazine group. Blood glucose levels were lower in the labetalol group at 6 hours of age (p < 0.05). No other differences were found between the two groups. The conclusion is that no clinical signs of adrenergic blockade have been found at 24 hours of age, and no negative effect of labetalol on the neonatal adaptation compared to hydralazine antihypertensive treatment was found. PMID- 8487155 TI - Characteristics of the spontaneous milk ejecting activity occurring during human lactation. AB - Continuous recordings of intramammary pressure performed in 158 normal lactating women, and 22 women during spontaneous labor were retrospectively analyzed in order to characterize spontaneous milk ejecting activity (SA). SA appeared as spurts of contraction waves as early as the first post-partum day and throughout the first two months of lactation. The spurts of SA differed from reflex milk ejection evoked by baby's suckling. It showed two different patterns: a) single contraction waves with a rapid rise time, a slow decay time, high amplitude and a short duration; b) multiple contraction waves with a longer rise and decay times, progressively decreasing intensity and a large duration depending on the number of contractions per spurt. The multiple pattern occurred in 34.2% (41/120) of patients at 2.7 +/- 0.1 days of post-partum and increased to 84.3% (59/70) at 34.5 +/- 1.2 days. Accordingly, duration and the area under contraction curves increased throughout lactation. Mammary gland sensitivity to exogenous oxytocin (OT) did not change during the 2 months studies. SA was significantly greater in full nursing mothers than in the partially nursing ones. The existence of a system for milk-ejection different from baby's suckling was further described. A neuroendocrine mechanism and the release of increasing amounts of OT are suggested as important factors in the control of this phenomenon. PMID- 8487156 TI - [Structure-activity relationship of flavonoids in suppressing rat liver lipid peroxidation]. AB - 145 flavonoids were studied for their inhibitory effects on the iron-induced lipid peroxidation in mitochondria obtained from rat livers. Of these compounds tested, 30, 57, 59, 67, 70, 72, 77, 102 and 110 (ED50 < or = 0.5 nmol/mg prot) showed distinctly more potent inhibitory activity than baicalein (ED50 < or = 5 nmol/mg prot) and 59 and 72 (ED50 < or = 0.05 nmol/mg prot) exhibited the most potent activity. In order to elucidate the relationships between substituents on the flavonoid skeleton and the biological activity, the quantitative structure activity relationships (QSAR) were analyzed by the adaptive least-squares (ALS) method for 142 flavonoids. The analysis has shown that the presence of the 1,4- and 1,2-hydroquinone in A-ring and/or B-ring of flavonoids and hydrophobicity of the molecule are responsible for the in vitro inhibitory activity. PMID- 8487157 TI - [A simultaneous determination of honokiol and magnolol in oriental pharmaceutical decoctions containing magnolia bark by ion-pair high-performance liquid chromatography]. AB - A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise simultaneous determination of honokiol (3', 5-di-2-propenyl-1, 1'-biphenyl-2,4'-diol) and magnolol (5,5'-di-2-propenyl-1,1' biphenyl-2,2'-diol) in oriental pharmaceutical decoctions containing Magnolia bark. An ODS column and a mixture of water involving 10 mM tetra-n-amylammonium bromide (TAA) and acetonitrile (4:6) as a mobile phase were used for the separation. Honokiol and magnolol were eluted without interference of other co existing components within 12 min. PMID- 8487158 TI - [Crystal morphological and habit investigations of crystalline drugs. II. Amobarbital, barbital and ephedrine hydrochloride]. AB - Crystal morphology, habit and refractive indices necessary for the analyses of amobarbital, barbital, phase III and ephedrine hydrochloride were studied using a polarizing microscope and partly using a reflexing goniometer. These substances, market products of Japanese Pharmacopoeia XII, were measured for optical properties including key refractive indices to confirm their modifications, and their possible facial angles along the zone of which axis is parallel to the elongated direction was also measured using a goniometer. Stereographic projections were drawn and the crystal habits of market products were shown by orthographic projections. It was also found that one of the key refractive indices of each modification was specially usable for the analyses of crystal habits including their crushed powders. PMID- 8487159 TI - [Interaction of camptothecin derivatives with human plasma proteins in vitro]. AB - The interactions of camptothecin (CPT) and its derivatives (CPT-11 and SN-38) with human plasma proteins (serum albumin (HSA) and alpha 1-acid glycoprotein (alpha 1-AGP)) were studied mainly by means of ultraviolet and fluorescence spectroscopy. The binding constants of lactone ring-opened forms (A form) of CPT and CPT-11 with HSA were larger than those of the intact lactone forms (L form). In the case of SN-38, there was no difference in the constants between A form and L form. The binding constant of CPT (A form) with HSA was larger than those of CPT-11 and SN-38. The presence of cisplatin, which is presumed to be coadministered with CPT derivatives, did not affect the interaction of CPT derivatives with HSA. Only L form of CPT-11 among the CPT derivatives examined interacted with alpha 1-AGP, followed by quenching the fluorescence of alpha 1 AGP. PMID- 8487160 TI - [Vicia graminea lectin or Vicia unijuga lectin-binding (Vgu) glycoproteins as new tumor-associated substances]. AB - The purification and serological and chemical properties of Vicia graminea lectin (VGA) and Vicia unijuga lectin (VUA) were described, and then the binding specificity of anti-M and -N antibodies and both the lectins was discussed in this review. On the basis of the facts that Vgu glycoproteins which react with either VGA or VUA but not with anti-M and -N antibodies and were not detected in human normal organ tissues and sera, were separated and identified as mucin-type glycoproteins with very high molecular weights from human cancerous organ tissues, ascitic fluids of cancer patients and cyst fluids of human ovarian cystadenoma in malignant, it was concluded that Vgu glycoproteins are new tumor associated substances. PMID- 8487161 TI - Strength of the lens capsule during hydroexpression of the nucleus. AB - In planned extracapsular cataract extraction, hydroexpression of the nucleus has been introduced to facilitate nucleus delivery when performing capsulorhexis. The hydroexpression technique induces a fluid pressure in the capsular bag, which may rupture the posterior capsule. In a human cadaver eye model the pressure at the capsule's rupture point was determined in 16 cadaver eyes and compared to the fluid pressure in the capsular bag during hydroexpression of the nucleus in 32 eyes. The posterior capsule was able to withstand a pressure of 59 +/- 10 mm Hg (mean +/- SD) without rupturing. During hydroexpression of the nucleus the pressure was less than 12 mm Hg (3 mm Hg to 12 mm Hg) when the diameter of the capsulorhexis opening was 5.5 mm or more (measurement in the anterior chamber). Thus hydroexpression of the nucleus seems to be a safe technique when the diameter of the capsulorhexis is 5.5 mm or more. PMID- 8487162 TI - Hydroexpression and viscoexpression of the nucleus through a continuous circular capsulorhexis. AB - When a continuous circular capsulorhexis (CCC) is performed, conventional nucleus expression may be impossible because of the strong capsular rim. Hydroexpression of the nucleus seems to overcome the problem if the capsulorhexis opening is large enough. Because a viscoelastic material may be an even more gentle tool than balanced salt solution (BSS), hydroexpression and viscoexpression were evaluated in 16 pairs of human cadaver eyes. The diameter of the capsulorhexis opening ranged from 4 mm to 6 mm; it was the same in each pair of eyes. Hydroexpression was performed in one eye using BSS and viscoexpression was performed in the fellow eye using sodium hyaluronate (Healon Yellow). The fluid pressure in the capsular bag was measured during both procedures. The pressure was higher during hydroexpression than during viscoexpression. The pressure difference between fellow eyes ranged from 0 to 32 mm Hg and was most marked when the CCC opening was small. This correlation was significant (P < .05). Viscoexpression may enhance the safety in cases with a small CCC opening or in those that are otherwise difficult. PMID- 8487163 TI - Assessment of the long-term corneal response to hydrogel intrastromal lenses implanted in monkey eyes for up to five years. AB - The biocompatibility of hydrogel intracorneal lenses (ICLs) implanted in monkey eyes was evaluated for periods ranging up to five years. Seventy-three plus or minus powered ICLs made of Lidofilcon A (68% water) or Lidofilcon B (79% water) were implanted following lamellar dissection with a microkeratome. Ten sham surgical procedures were performed without ICL implantation as controls. Eyes were followed for up to five years by slitlamp biomicroscopy and specular microscopy. Light and transmission electron microscopic evaluations of enucleated eyes were performed at various intervals. Minimal tissue reaction was noted; both hydrogel materials appeared to be equally well tolerated. Failures usually occurred as a result of microkeratome problems encountered during surgery. Histopathological changes to the cornea included epithelial thinning anterior to the thickest portion of the ICL, fibroblastic activity along the ICL-stromal interface, and deposition of an amorphous extracellular material adjacent to the ICL. These observations did not appear to be clinically significant as the eyes were quiet by slitlamp examination. Removal of three ICLs eight to ten months prior to enucleation restored the normal histological characteristics of the cornea. The endothelial cell density of ICL-implanted eyes decreased by 4.3% (n = 17) six months after surgery but remained stable thereafter. The variation in endothelial cell area and percentage of hexagonal cells did not change over 50 months. The results appear to demonstrate that high water content synthetic ICLs can be well tolerated in the monkey cornea for up to five years. PMID- 8487164 TI - Evaluation of intraocular pressure fluctuations with differing phacoemulsification approaches. AB - Simultaneous two-camera video tracings of phacoemulsification surgery and intraocular pressure fluctuations were made. The fluctuations were transmitted to a quartz pressure transducer through a chamber maintainer that was plugged into the anterior chamber. The transducer was connected to a monitor and recorder calibrated to measure pressure variations between -8.6 and +60 mm Hg. Using common audio for synchronization, the pressure tracings were keyed over the surgical videos and combined in a single film. High, medium, and low inflow volume techniques used by many surgeons exhibiting commensurately higher or lower intraocular pressure fluctuations were scrutinized. Methods to increase inflow volume without a proportionate pressure increase were devised. PMID- 8487165 TI - Corneal endothelial cell transplantation using Descemet's membrane as a carrier. AB - Rabbit corneal endothelial cells were transplanted into the right eyes of four New Zealand white rabbits using bovine Descemet's membrane as a cell carrier. Descemet's membranes were dissected from cow eyes, flattened on 36 mm culture dishes, and cut into discs with a 6 mm trephine. Rabbit corneal endothelial cells were seeded onto the discs and maintained in tissue culture conditions for seven days until a complete monolayer with a cell density of 3,000 cells/mm2 was formed. Before transplantation, corneal edema was induced in the host animals by an endothelial scrape wound, which removed the corneal endothelium. Five weeks later, the animals were prepared for transplantation. A corneal button was cut and placed on a dissection table so the host Descemet's membrane could be removed. The donor Descemet's membrane with a complete monolayer of rabbit corneal endothelial cells was placed on the stroma of the corneal button. To keep the donor membrane in place, the button was cauterized at three peripheral points and sutured back into the host eye. Prednisolone sodium phosphate eyedrops and dexamethasone eyedrops and ointment were applied twice daily during the post operative period. All grafts stayed clear for a period of 12 to 17 weeks. This study shows the potential for using Descemet's membrane as a carrier for corneal endothelial cell transplantation. PMID- 8487166 TI - Changes in corneal shape after suture cutting using the argon laser for postoperative astigmatism following cataract extraction. AB - We studied the changes in corneal shape after suture cutting with an argon laser to reduce corneal astigmatism following cataract extraction. Sixty-two patients who exhibited high with-the-rule astigmatism (> 3 diopters [D]) following extracapsular lens extraction had argon laser suture cutting. The patients were classified into three groups: Group A comprised 30 patients whose sutures were cut two to three months after planned extracapsular cataract extraction (p-ECCE); Group B consisted of eight patients who had the same treatment five to nine months after p-ECCE; Group C comprised 24 patients who had the treatment one to two months after phacoemulsification (PE). The dioptric reduction of corneal astigmatism (the percent reduction of astigmatism) was 1.83 +/- 0.98 D (37.4 +/- 18.3%) in Group A, 3.20 +/- 2.35 D (55.6 +/- 34.4%) in Group B, and 2.08 +/- 1.20 D (41.4 +/- 20.4%) in Group C. There was no statistical significance in the dioptric reduction and the percent reduction among Groups A, B, and C. This suggests that the wound size and time of cutting are not directly correlated to the effect of argon laser suture cutting. To examine the relationship between the effect and changes in corneal shape from suture cutting, we divided the patients into two subgroups; one was Subgroup (+) in which the percent reduction of astigmatism was above 25%; the other was Subgroup (-) in which the percent reduction was below 25%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487167 TI - Enhancement of the ocular bioavailability of topical tobramycin with use of a collagen shield. AB - We compared the ocular bioavailability in rabbits of 0.3% tobramycin applied with a collagen shield with eyedrop tobramycin application. Groups of rabbits received either (1) a collagen shield presoaked in tobramycin with a tobramycin drop before and after shield application (Shield) or (2) three drops of tobramycin (Drops). Postmortem samples of the cornea, conjunctiva, and aqueous humor were obtained at various intervals after shield application or drop instillation. The corneas in a second set of rabbits were anesthetized and then chemically abraded with n-heptanol before receiving the same two dosing regimens as in the groups with intact corneas. At nearly all times in all three tissues, the Shield groups had higher mean concentrations of tobramycin than the Drops groups. The area under the concentration-time curve for the Shield group relative to the Drops group was 5.0- to 16.1-fold greater for rabbits with intact corneas (P < .05), and 1.8- to 3.7-fold greater for rabbits with abraded corneas (P < .05). The use of collagen shields together with standard ophthalmic concentrations of tobramycin may be useful in achieving higher concentrations of topically delivered drugs into the anterior segment of the eye. PMID- 8487168 TI - Conversion to small-incision phacoemulsification: experience with the first 50 eyes. AB - Conversion from extracapsular cataract surgery to small-incision phacoemulsification is inevitably associated with a learning curve. Retrospective analysis of one surgeon's learning curve was carried out on the first 50 consecutive operations using small-incision phacoemulsification. Parameters were evaluated, including postoperative acuity and astigmatism at eight days, three weeks, three months, and six months. A comparison of the results of the first 25 operations and the subsequent 25 showed statistically significant differences only in acuity at eight days and cylinder at three months. The most frequent complication was corneal edema lasting at least one week. With careful preparation, proper patient selection, and meticulous technique, the learning curve for converting from extracapsular surgery to small-incision phacoemulsification does not necessarily increase the complication rate. PMID- 8487169 TI - Distance visual acuity with diffractive multifocal and monofocal intraocular lenses. AB - A series comprising 166 eyes implanted with monofocal intraocular lenses and 143 eyes with diffractive multifocal lenses was examined. The implantations were performed intermittently and consecutively during 18 months by one surgeon using the same technique. The mean postoperative visual acuity was 0.5 line higher in the monofocal than in the multifocal group, a significant difference (P < .01). The better performance of the monofocal lens was almost constant in all six age groups (range: < or = 65 years to > or = 86 years). PMID- 8487170 TI - Contrast sensitivity and glare in patients with a diffractive multifocal intraocular lens. AB - Contrast sensitivity was measured in 25 patients who had a multifocal diffractive intraocular lens and in 23 control patients with a monofocal lens in four simulated light conditions: (1) daylight, (2) daylight with peripheral glare, (3) twilight, (4) twilight with central glare. In normal daylight and twilight, contrast sensitivity of the multifocal group was significantly lower than the control group's (P < .05). The difference was 0.13 log units for the multifocal group and 0.17 log units for the control group (mean value across the tested frequency from 1.5 to 18 cycles/deg). Peripheral glare reduced contrast sensitivity under daylight conditions in both groups (P < .05), but the loss did not differ significantly between the two (P > .05). Central glare reduced contrast sensitivity under twilight conditions in both groups (P < .05), with the greatest loss in the multifocal patients (P < .001). We conclude that the most significant loss of contrast sensitivity in patients with the diffractive multifocal intraocular lens is found with central glare under twilight conditions. PMID- 8487171 TI - Long-term results and biocompatibility of heparin-surface-modified intraocular lenses. AB - A prospective in vivo study of 50 intraocular lenses was done to document the long-term results and biocompatibility of heparin-surface-modified poly(methyl methacrylate) posterior chamber lenses. Continuous curvilinear capsulorhexis and phacoemulsification were performed throughout and examinations were by slit-lamp and specular microscopy. Decentrations of more than 1 mm were seen in 4% of eyes. Stress folds from the haptic traction forces were detected in 16%. A posterior capsulotomy was performed in 10% because of fibrosis or Elschnig pearl formation. Fine fibers were found on the lens surface in 76%. During the first postoperative days only a moderate number of fibroblast-like cells was observed. Foreign-body giant cells were seen in 8%. All cases with foreign-body giant cells had posterior synechias. Visual performance and clinical results were comparable to those of other well-approved intraocular lenses. The low percentage of cellular reaction on the lens surface suggests good biocompatibility. PMID- 8487172 TI - Postoperative complications and uncorrected acuities after implantation of plate haptic silicone and three-piece silicone intraocular lenses. AB - Complications after implantation of 503 plate haptic silicone intraocular lenses were compared with those after implantation of 253 silicone three-piece polypropylene loop lenses. The uncorrected visual acuities were also compared. Capsulorhexis and endocapsular phacoemulsification were used in all cases. The incidence of cystoid macular edema and posterior capsule opacification requiring a YAG capsulotomy were significantly higher in the cases with polypropylene three piece loop lenses. Pigment dispersion and decentration also occurred more frequently in this group. This is probably because the 10.5 mm plate haptic lens is more rigid than the polypropylene loop lens. It also fixates more posteriorly within the capsular bag than the anteriorly located polypropylene lens. Patients implanted with a plate haptic silicone intraocular lens through a 3.5 mm scleral incision had significantly better uncorrected visual acuity at five to six weeks postoperatively than those with a three-piece silicone lens that required a 4.5 mm incision for insertion. PMID- 8487173 TI - Surgical complications and visual acuity results in 536 cases of plate haptic silicone lens implantation. AB - Implantation of a plate haptic intraocular lens was planned in 536 cases. This paper reports the uncorrected and corrected visual acuities and complications in 33 patients in whom there were surgical complications that prevented implantation of the plate haptic lens. Excluding five patients (15%) who had pre-existing pathology, 21 (75%) had uncorrected acuity of 20/40 or better and 27 (96%) had corrected acuity of 20/40 or better five to six weeks postoperatively. The plate haptic lens can only be used with capsulorhexis and an intact anterior capsular rim and posterior capsule. Two alternative backup lens styles--a loop lens for placement in the torn bag or the sulcus and an anterior chamber lens--have to be in the operating room for each surgery. PMID- 8487175 TI - Features of a modern retrobulbar anesthetic injection for cataract surgery. AB - No significant complications including retrobulbar orbital hemorrhage after retrobulbar anesthetic block were identified in a retrospective review of 3,415 consecutive cataract surgical cases blocked and performed by one surgeon. The technique for retrobulbar injections using a disposable retrobulbar needle is described in detail. All injections were deliberately retrobulbar, directed toward the inferior temporal muscle cone, and were given immediately prior to cataract surgery by the surgeon. PMID- 8487176 TI - Topical anesthesia for small incision self-sealing cataract surgery. A prospective evaluation of the first 100 patients. AB - Small incision self-sealing cataract surgery has created the opportunity to use less invasive anesthesia. One hundred patients were evaluated in a prospective study using a new technique of topical anesthesia to allow small incision construction, intercapsular phacoemulsification, and small incision intraocular lens implantation without a peribulbar or retrobulbar injection. This study demonstrated that topical anesthesia avoids the risk of globe perforation, retrobulbar hemorrhage, and prolonged postoperative akinesia of the eye and is effective for intraoperative anesthesia for cataract surgery. PMID- 8487174 TI - Suture to limbus distances in eyes with a posterior chamber intraocular lens implanted by scleral fixation. AB - This study used linear regression to analyze the correlation between the location of transscleral sutures and the postoperative visual acuity, refraction, and anterior chamber depth in eyes with posterior chamber intraocular lenses implanted by scleral fixation. The suture-to-limbus distance at the 12 o'clock and 6 o'clock positions averaged 2.4 mm and 1.7 mm, respectively. Suture location had no statistically significant relationship with postoperative acuity, spherical equivalent, astigmatism, or anterior chamber depth. PMID- 8487177 TI - New theoretical matrix formula for intraocular lens calculation using the optimal bending factor. AB - By applying Gaussian optics we propose a new matrix formula model for intraocular lens (IOL) calculation that yields not only IOL optical power for a particular eye but also an evaluation of the bending factor of different IOL optical designs. This option improves IOL selection and results in the best possible optical image, a function dependent on the IOL's bending factor. This formula is a new approach to IOL calculation and may be useful in designing IOLs for abnormally hyperopic or myopic eyes. Optimal IOL power and design should both be considered in IOL calculation, which may improve the optical and clinical results of IOL implantation in the aphakic patient. The radius of the cornea is assumed to be spherical, and aspherical curves of the cornea may influence the optimal "bending" or shape factor of a lens. PMID- 8487178 TI - Ultraviolet radiation and cataract development in the U.S. Virgin Islands. AB - Ultraviolet (UV) radiation is one of several factors thought to cause cataracts. This retrospective study of a population in the West Indies who had had voluntary cataract surgery sought to determine the effect of a relatively high level of UV exposure and the type of exposure. This population had a high incidence of nuclear/brunescent cataracts, which correlates with the type of radiation present. Yet the results indicate that although chronic exposure to UV radiation may play a role in the type and location of cataracts, other factors (e.g., age, diabetes) are more important in their formation. PMID- 8487179 TI - Treatment of anterior chamber fibrin following cataract surgery with tissue plasminogen activator. AB - Three patients who developed anterior chamber fibrinous exudates after cataract surgery were treated with tissue plasminogen activator injected into the anterior chamber. There was prompt dissolution of the fibrinous exudates and no observed complications. When fibrinous exudates occur in high-risk patients after cataract surgery, tissue plasminogen activator provides an excellent means of clearing the fibrin. PMID- 8487180 TI - Oil-drop cataracts. AB - The oil-drop cataract is a common yet often overlooked cause of progressive vision loss. Although the nuclear change can be subtle on slitlamp biomicroscopic examination, retinoscopy reveals the classic oil droplet silhouetted against the red reflex. We present seven patients with oil-drop cataracts referred for neuro ophthalmologic evaluation because of unexplained vision loss. All had been evaluated by multiple physicians and had had extensive diagnostic testing. The patients were between 36 and 69 years old with visual acuities from 20/20 to 20/400. The neuro-ophthalmologic evaluation in all patients was normal except for lenticular nuclear changes, best appreciated with retinoscopy. PMID- 8487181 TI - Excimer laser ablation of conjunctival epithelial melanosis. AB - Two patients with conjunctival epithelial melanosis received a 193 nm argon fluoride excimer laser treatment. In both patients the melanosis was easily removed with a smoothing technique using the excimer laser. The ablated area showed normal appearing conjunctiva. The lesion did not recur during the eight month follow-up. Therapeutically, the excimer laser can be used to treat benign conjunctival lesions as well as superficial corneal diseases. PMID- 8487183 TI - Blade designed for improved safety and accuracy in radial keratotomy. PMID- 8487184 TI - Consultation section. Loss of the lens nucleus. PMID- 8487182 TI - Visual disability resulting from a dislocated intraocular lens. AB - Complications may arise from the failure to remove a dislocated intraocular lens, even when it appears to rest in a benign position and pose no problems. We examined a patient with a second intraocular lens left in the inferior vitreous cavity. Shifting the loose lens resulted in eventual complications and visual disability; removing the dislocated lens and replacing the functional intraocular lens yielded good results. PMID- 8487185 TI - Simple method to calculate the surgically induced refractive change. PMID- 8487186 TI - More on calculating the surgically induced refractive change: two easy solutions. PMID- 8487187 TI - Capsular tears with irrigation/aspiration system. PMID- 8487188 TI - Glare and other optical considerations with ovoid implant designs. PMID- 8487189 TI - The spring phenomenon with dual placement lenses. PMID- 8487190 TI - Ca2+ levels in myotubes grown from the skeletal muscle of dystrophic (mdx) and normal mice. AB - 1. Myotubes were grown in culture from normal (C57BL/ScSn) and mdx mice and the cytosolic [Ca2+] was monitored through development (5-21 days in culture) using fura-2 loaded via ionophoresis. Simultaneous measurements of the membrane potential and cytosolic [Ca2+] were made in normal and mdx myotubes before, during and after stimulation by action potentials elicited following anode break excitation. All experiments were undertaken at 22 degrees C. All data are expressed as means +/- S.E.M. 2. A new method was developed which enabled accurate determination of the fluorescence characteristics of fura-2 in murine skeletal muscle fibres. In the under in vitro conditions by 14.60 +/- 0.05, 9.40 +/- 0.15 and 6.90 +/- 0.43% respectively. 3. The resting cytosolic [Ca2+] in the mdx myotubes was consistently higher than in the normal myotubes throughout the developmental period measured. Overall, the resting cytosolic [Ca2+] in mdx myotubes (134 +/- 9 nM, n = 22) was twofold higher than in normal myotubes (66 +/ 6 nM, n = 26). After stimulation (one to three action potentials) the cytosolic [Ca2+] of both mdx and normal myotubes remained elevated. The mdx myotubes (236 +/- 55 nM, n = 5) again had approximately double the cytosolic [Ca2+] of normal myotubes (109 +/- 19 nM, n = 9). 4. The time course and amplitude of the Ca2+ responses measured in the mdx and normal myotubes after action potential stimulation were variable. Two categories of Ca2+ response were observed in mdx and normal myotubes, the first consisted of a small, slow rise in [Ca2+] that remained elevated and the second consisted of a rapid (time to peak 7.4 +/- 1.5 ms) (n = 8) rise in [Ca2+] with amplitudes in the range 61-773 nM and a [Ca2+] decay rate constant of 4.35 +/- 1.57 s-1 (n = 8) (range 0.96-15 s-1). 5. In conclusion, the elevated cytosolic [Ca2+] reported here through development of cultured mdx myotubes suggests that this genetic disorder results in a defect which compromises the ability of the myotubes to strictly regulate cytosolic [Ca2+]. The results are consistent with the presence of functionally abnormal Ca2+ channels recently reported in mdx myotubes. PMID- 8487191 TI - The cutaneous vascular axon reflex in humans characterized by laser Doppler perfusion imaging. AB - 1. Laser Doppler perfusion imaging was used to map the cutaneous vascular axon response induced by trains of electrical skin stimuli (1 ms, 2 Hz) on the dorsum of the hand, finger and foot in twenty-four healthy subjects. Conduction anaesthesia was applied to nerves supplying the stimulated skin areas. Subtraction of images recorded before and after stimulation was used for data analysis of the intensity and area of the response. 2. The stimulation evoked a localized perfusion increase around the stimulating electrode which lasted approximately 30 min and increased in intensity and area with increasing stimulation strength to a maximum at 20 pulses and 20 mA. The intensity and area of the response was greater on the hand than on the foot. 3. Approximating the response area as a circle, the maximal perfusion increase in the hand extended 9 +/- 3 mm (mean +/- S.D.) outside the perimeter of the stimulating electrode. When stimulating within skin which had been subjected to surface anaesthesia, no response occurred, but when stimulating at the border of surface-anaesthetized skin, the perfusion increase extended 2 +/- 1 mm (mean +/- S.D.) into anaesthetized skin. 4. The results show that the perfusion increase must have been due in part to impulse conduction to, and release of transmitters from, axon endings terminating in skin outside the contact area of the probe. It is concluded that the area of perfusion increase corresponds to the size of the receptive fields of afferent polymodal C fibres. PMID- 8487192 TI - Magnetic coil stimulation of straight and bent amphibian and mammalian peripheral nerve in vitro: locus of excitation. AB - 1. According to classical cable theory, a magnetic coil (MC) should excite a linear nerve fibre in a homogeneous medium at the negative-going first spatial derivative of the induced electric field. This prediction was tested by MC stimulation of mammalian phrenic and amphibian sciatic nerve and branches in vitro, immersed in Ringer solution within a trough, and identifying the sites of excitation by recording responses of similar latency to local electrical stimulation. Subsequently, the identified sites of excitation were compared with measurements of the induced electric field and its calculated first spatial derivative. A special hardware device was used to selectively reverse MC current direction and to generate predominantly monophasic- or polyphasic-induced pulse profiles whose initial phases were identical in polarity, shape and amplitude. When using the amphibian nerve preparation, a complication was excitation at low threshold points related to cut branches. 2. Reversal of monophasic current resulted in latency shifts corresponding approximately to the distance between induced cathode and anode. The location of each site of excitation was at, or very near, the negative-going first spatial derivative peaks of the induced electric field measured parallel to the straight nerve. Significantly, excitation of the nerve did not occur at the peak of the induced electric field above the centre of the 'figure of eight' MC junction. 3. A polyphasic pulse excited the nerve at both sites, by the negative-going first phase at one location, and approximately 150 microseconds later, by the reversed negative-going second phase at the other location. Polyphasic and monophasic pulses elicited responses with similar latency when the induced current flowed towards the recording electrode. 4. Straddling a nerve with non-coding solid lucite cylinders created a localized spatial narrowing and increase in the induced electric field, resulting in a lowered threshold of excitation. The corresponding closer spacing between first spatial derivative peaks was exhibited by a significant reduction in latency shift when MC current direction was reversed. 5. When a nerve is bent and the induced current is directed along the nerve towards the bend, the threshold of excitation is reduced there. Increasing the angle of the bend from 0 deg to more than 90 deg graded the decrease in threshold. 6. In a straight nerve the threshold was lowest when current was directed towards the cut end.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487193 TI - The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats. AB - 1. We investigated the central role of corticotrophin-releasing factor (CRF-41) in psychological stress-induced responses, including cardiovascular, thermoregulatory and locomotive activity in free-moving rats. 2. Psychological stress was induced by cage-switch stress. After rats were placed in the novel environment, blood pressure, heart rate, body temperature and locomotive activity significantly increased. The intracerebroventricular (I.C.V.) injection of alpha helical CRF(9-41), a CRF-41 receptor antagonist, significantly attenuated the stress-induced hypertension, tachycardia, hyperthermia and increase in locomotive activity. However, in unstressed rats, the I.C.V. injection of alpha-helical CRF(9-41) had no effect on physiological parameters measured in this study. 3. In unstressed rats, the I.C.V. injection of CRF-41 (1 microgram and 10 micrograms) increased blood pressure, heart rate, body temperature and locomotive activity in a dose-dependent manner. The changes in these responses were quite similar to those observed during cage-switch stress. 4. The results suggest that central CRF 41 plays an important role in psychological stress-induced hypertension, hyperthermia, tachycardia and increase in locomotive activity. However, it is likely that central CRF-41 does not contribute to normal cardiovascular and body temperature regulation when rats are free from stress. PMID- 8487194 TI - Effects of inorganic phosphate analogues on stiffness and unloaded shortening of skinned muscle fibres from rabbit. AB - 1. We examined the effects of aluminofluoride (AlFx) and orthovanadate (Vi), tightly binding analogues of orthophosphate (Pi), on the mechanical properties of glycerinated fibres from rabbit psoas muscle. Maximum Ca(2+)-activated force, stiffness, and unloaded shortening velocity (Vus) were measured under conditions of steady-state inhibition (up to 1 mM of inhibitor) and during the recovery from inhibition. 2. Stiffness was measured using either step or sinusoidal (1 kHz) changes in fibre length. Sarcomere length was monitored continuously by helium neon laser diffraction during maximum Ca2+ activation. Stiffness was determined from the changes in sarcomere length and the corresponding changes in force. Vus was measured using the slack test method. 3. AlF chi and Vi each reversibly inhibited force, stiffness and Vus. Actively cycling cross-bridges were required for reversal of these inhibitory effects. Recovery from inhibition by AlF chi was 3- to 4-fold slower than that following removal of V1. 4. At various degrees of inhibition, AlF chi and Vi both inhibited steady-state isometric force more than either Vus or stiffness. For both AlF chi and Vi, the relatively greater inhibition of force over stiffness persisted during recovery from steady-state inhibition. We interpret these results to indicate that the cross-bridges with AlF chi or Vi bound are analogous to those which occur early in the cross-bridge cycle. PMID- 8487195 TI - The effects of MgADP on cross-bridge kinetics: a laser flash photolysis study of guinea-pig smooth muscle. AB - 1. The effects of MgADP on cross-bridge kinetics were investigated using laser flash photolysis of caged ATP (P3-1(2-nitrophenyl) ethyladenosine 5' triphosphate), in guinea-pig portal vein smooth muscle permeabilized with Staphylococcus aureus alpha-toxin. Isometric tension and in-phase stiffness transitions from rigor state were monitored upon photolysis of caged ATP. The estimated concentration of ATP released from caged ATP by high-pressure liquid chromatography (HPLC) was 1.3 mM. 2. The time course of relaxation initiated by photolysis of caged ATP in the absence of Ca2+ was well fitted during the initial 200 ms by two exponential functions with time constants of, respectively, tau 1 = 34 ms and tau 2 = 1.2 s and relative amplitudes of 0.14 and 0.86. Multiple exponential functions were needed to fit longer intervals; the half-time of the overall relaxation was 0.8 s. The second order rate constant for cross-bridge detachment by ATP, estimated from the rate of initial relaxation, was 0.4-2.3 x 10(4) M-1 s-1. 3. MgADP dose dependently reduced both the relative amplitude of the first component and the rate constant of the second component of relaxation. Conversely, treatment of muscles with apyrase, to deplete endogenous ADP, increased the relative amplitude of the first component. In the presence of MgADP, in-phase stiffness decreased during force maintenance, suggesting that the force per cross-bridge increased. The apparent dissociation constant (Kd) of MgADP for the cross-bridge binding site, estimated from its concentration dependent effect on the relative amplitude of the first component, was 1.3 microM. This affinity is much higher than the previously reported values (50-300 microM for smooth muscle; 18-400 microM for skeletal muscle; 7-10 microM for cardiac muscle). It is possible that the high affinity reflects the properties of a state generated during the co-operative reattachment cycle, rather than that of the rigor bridge. 4. The rate constant of MgADP release from cross-bridges, estimated from its concentration-dependent effect on the rate constant of the second (tau 2) component, was 0.35-7.7 s-1. To the extent that reattachment of cross-bridges could slow relaxation even during the initial 200 ms, this rate constant may be an underestimate. 5. Inorganic phosphate (Pi, 30 mM) did not affect the rate of relaxation during the initial approximately 50 ms, but accelerated the slower phase of relaxation, consistent with a cyclic cross-bridge model in which Pi increases the proportion of cross-bridges in detached ('weakly bound') states.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487196 TI - 31P nuclear magnetic resonance studies on the glycogenolysis regulation in resting and contracting frog skeletal muscle. AB - 1. Regulation of glycogenolysis in frog skeletal muscle at rest and following contraction was studied by measuring the concentration of phosphate-containing metabolites and the intracellular pH (pHi) in CN-treated muscles, in which oxidative phosphorylation was inhibited by NaCN, using the 31P nuclear magnetic resonance (NMR) technique. 2. When CN-treated muscles were kept at rest, the phosphocreatine (PCr) concentration very slowly decreased with time with a corresponding increase of the inorganic phosphate (Pi) concentration, while the ATP concentration remained unchanged. The pHi changed in the alkaline direction for the first 3 h, and then started to change in the acidic direction. 3. When CN treated muscles were tetanized for 10 s, the PCr concentration decreased with a corresponding increase of the Pi concentration and acidification of pHi, while the ATP concentration remained unchanged. 4. When CN-treated muscles were tetanized repeatedly (each for 2 s) at constant intervals, the pHi changed in the alkaline direction following the first and the second tetani, and then changed in the acidic direction following the subsequent tetani, indicating that the consumed ATP is first replenished by the Lohmann reaction, while glycogenolysis starts only when the total amount of contractile activity exceeds a critical value. 5. Irrespective of whether CN-treated muscles were kept at rest or tetanized repeatedly, the Pi concentration increased to about 8 mM (mmol/kg wet muscle) when glycogenolysis started, suggesting that the onset of glycogenolysis in CN-treated muscles is regulated by the Pi concentration. 6. The 'internal' buffering power of muscle cytosol was estimated to be 35 mM H+/pH unit in anaerobic muscles and 25 mM H+/pH unit in CN- and iodoacetic acid (IAA)-treated muscles. The 'internal' buffering power contains a contribution due to flux of carbon dioxide and lactic acid across the cell membrane. Evidence indicated that lactic acid flux is small. PMID- 8487197 TI - Effects of internal and external Na+ ions on inwardly rectifying K+ channels in guinea-pig ventricular cells. AB - 1. The effects of internal and external Na+ ions on the inwardly rectifying K+ channel were studied in guinea-pig ventricular cells. 2. Single-channel currents through the inwardly rectifying K+ channel were recorded in the open cell attached or inside-out configuration at 150 mM internal K+ and either 150 or 25 mM external K+. Internal Na+, at a concentration of 5-40 mM, reduced the unitary amplitude of the outward current. No increase in open-channel current noise was detected with the filter cut-off frequency of 3 kHz. Substate behaviour seen with internal Mg2+ at a micromolar level was not observed. The inward currents were little affected by internal Na+. 3. The unitary current-voltage relation rectified inwardly in the presence of internal Na+ in a concentration-dependent manner. 4. Outward unitary currents were normalized to those measured in the absence of Na+. The normalized current-voltage relation was shifted in the negative direction by 20-25 mV by decreasing external K+ from 150 to 25 mM, indicating that the blocking effect increases with low external K+ when compared at a fixed voltage. 5. The normalized current-Na+ concentration curve was fitted by a one-to-one binding curve at each voltage. In a semi-logarithmic plot of dissociation constant versus membrane potential, data points for 150 and 25 mM external K+ were fitted by straight lines with nearly the same slope. The dissociation constant at 0 mV is 154 mM in 150 mM external K+ and 89 mM in 25 mM external K+. The voltage dependence of dissociation constants gives a value for the effective valency of the Na+ ion of around 0.5. 6. To study effects of external Na+, single-channel currents were recorded with pipette solutions containing 125 mM Na+, 125 mM choline or 125 mM N-methyl-D-glucamine (NMDG) in addition to 25 mM K+. Current amplitude was smaller with choline than with Na+ or NMDG. The reduction in current amplitude with choline was more evident in the inward current, resulting in a stronger outward rectification of the current voltage relation. This finding and prolonged mean open time (see Summary point 7) was interpreted by assuming that choline is an open-channel blocker. 7. The lifetimes of the openings in the inward currents were distributed according to a single exponential. The mean open time with Na+ was similar to that with NMDG, which decreased with hyperpolarization. The mean open time with choline was much longer and less voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487198 TI - Electrical and integrative properties of rabbit sympathetic neurones re-evaluated by patch clamping non-dissociated cells. AB - 1. Voltage recordings were performed on non-dissociated sympathetic neurones from rabbit coeliac ganglia using the whole-cell configuration of the patch clamp technique. 2. Cells were classified depending on their firing pattern as silent cells (63%) producing either phasic (24%) or tonic (76%) spike discharge in response to depolarizing currents, and pacemaker cells (37%). 3. All the cells produced large overshooting spikes and prolonged postspike after hyperpolarization. The peak-to-peak spike amplitude was 113.8 +/- 1 mV. Spikes were shortened and the after-hyperpolarization was suppressed when calcium channel blockers (Cd2+ and La3+) were added. 4. Silent cells have a resting potential of -58.8 +/- 1.5 mV. At potentials ranging from -50 to -90 mV, the input impedance was 490 +/- 27 M omega at 22-24 degrees C and 426 +/- 47 M omega at 35-36 degrees C. The time constant at voltages corresponding to the high input impedance region was 126 +/- 7 ms at 22-24 degrees C and 86 +/- 7 ms at 35-36 degrees C. 5. The firing frequency of the pacemaker cells was 3.2 +/- 0.5 Hz at 35-36 degrees C in the presence of nicotinic blockers. Evidence is given that the firing did not result from cell injury but was induced by an intrinsic pacemaker mechanism. Input impedance of pacemaker neurones was 580 +/- 47 M omega at 22-24 degrees C and 473 +/- 56 M omega at 35-36 degrees C. 6. Most of the pacemaker cells (63%) were motoneurones, since they were antidromically fired by stimulating post-ganglionic nerves. In addition, they received synaptic inputs from both preganglionic fibres (splanchnic nerves) and the periphery (postganglionic nerves). Long-lasting depolarizations were induced in either silent or pacemaker cells by single shocks applied to pre- and postganglionic nerves. 7. Slowly rising voltage ramps revealed the presence of an N-shaped current-voltage relationship in voltage clamped pacemaker cells. The negative slope was located in a subthreshold voltage range, between -83.4 +/- 1.4 and 59.0 +/- 1.8 mV. It was induced by the activation of a low threshold persistent inward current. Although it was tiny (22 +/- 3 pA at its peak level) this current brought the null-current voltage up to -41.0 +/- 1.4 mV, which resulted in continuous firing. 8. Due to the instability introduced by the N-shaped I-V relationship, pacemaker cells can display bistable behaviour characterized by hyperpolarizing responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487199 TI - Correlations between myosin heavy chain isoforms and mechanical parameters in rat myometrium. AB - 1. The relations between mechanical parameters and myosin heavy chain isoforms were studied in myometrial smooth muscle from ovariectomized rats (O) and oestrogen-treated, ovariectomized rats (E). 2. Treatment of the rats for three days with beta-oestradiol (2 micrograms kg-1 day-1) 2-4 weeks postsurgery, produced maximal changes in uterine mass and myosin content of approximately threefold. 3. Myosin heavy chain isoform SM1 (204 kDa) was increased from 65.5 +/ 0.8% to 72.9 +/- 0.6% of the total isoform species (P < 0.001, n = 24, O and E respectively) after oestrogen treatment. 4. To avoid complications associated with activation processes, mechanical parameters were measured in permeabilized myometrial fibre bundles activated at a calcium concentration of 12.6 microM. After oestrogen treatment the maximum velocity of shortening (Vmax) measured by the slack test increased from 0.044 +/- 0.006 of the reference length (Lo) s-1 to 0.101 +/- 0.006 Lo s-1, and maximal isometric force (Pmax) increased from 23.3 +/ 4.4 mN mm-2 to 74.1 +/- 13.9 mN mm-2 (P < 0.001, n = 24, respectively). Series elasticity and the half-time to peak force were not significantly altered. 5. Both Vmax and Pmax correlated significantly with percentage SM1 in O and E fibre bundles (r = 0.61 and 0.56, n = 48 fibres; or r = 0.87 and 0.89, n = 8 grouped data per rat). Vmax, however, was only weakly correlated with Pmax (r = 0.39, n = 48). 6. To assess the relative significance of the correlation between Vmax and the percentage of SM1 and that between Vmax and Pmax, we used a multiple regression analysis with the model Vmax = intercept + beta 1 x % SM1 + beta 2 x Pmax, where intercept, beta 1 and beta 2 are regression parameters. This analysis (n = 48) indicated that Vmax was significantly dependent on the percentage of SM1 (P < 0.0002) but not on Pmax (P < 0.61). 7. There were no significant differences in the levels of myosin light chain phosphorylation between O and E fibre bundles, indicating that light chain phosphorylation is unlikely to be the basis for the differences in mechanical parameters demonstrated by these fibres. PMID- 8487200 TI - Effect of external cation concentration and metabolic inhibitors on membrane potential of human glial cells. AB - 1. The effect on membrane potential (Em) of low external [K+]o, [Na+]o and [Ca2+]o and of metabolic inhibitors was studied in cultured human glial cells (U 787CG) and human glioma cells (Tp-483MG and U-251MG). Whole cells were voltage or current clamped with the tight-seal recording technique. 2. Em was -76 and -80 mV in glial and glioma cells (mean values in U-787CG and U-251MG, respectively) in a reference external solution with 3.0 mM K+. K(+)-free external solution caused a rapid and reversible depolarization of these cells by about 26 and 42 mV (respectively). 3. Block of K+ channels with 1 mM Ba2+ in external solution rapidly depolarized the cells (U-251MG) by about 35 mV. 4. Na(+)-free solutions caused a delayed depolarization by 40-50 mV, which was slowly reversible (in 2 min). 5. Ouabain (1 mM) depolarized the cells by about 4 mV. It did not prevent the effect of K(+)-free solution. 6. Ca(2+)-free external solution rapidly depolarized the cells to Em about -17 mV. The combination of either Na(+)-K(+) free or Na(+)-Ca(2+)-free solution transiently repolarized the cell, which indicated that the K+ selectivity of the membrane was decreased in both K(+)- and Ca(2+)-free solutions. 7. Metabolic inhibitors (carbonyl cyanide p trifluoromethoxy-phenylhydrazone (FCCP) and 2,4-dinitrophenol (DNP)) rapidly and reversibly depolarized the cells. This effect was not prevented by intracellular perfusion of a strong Ca(2+)-buffering solution. 8. Voltage clamp revealed only minor changes (< 20%) in the leak conductance (g) of cells that were depolarized by the above-mentioned solutions. 9. Positive polarizing current elicited (in some cells) a regenerative depolarization. The threshold for depolarization was less in low external [K+]o. 10. It is concluded (a) that the resting potential of these glial cells depends on ion channels that are K+ selective only in the presence of external Ca2+ and K+ and (b) that this K+ selectivity may require that Em is near the reversal potential for potassium (EK), and (c) that the action of metabolic inhibitors (DNP and FCCP) is different from that in neurones. PMID- 8487201 TI - Exercise-induced diaphragmatic fatigue in healthy humans. AB - 1. Twelve healthy subjects (33 +/- 3 years) with a variety of fitness levels (maximal oxygen uptake (VO2, max) = 61 +/- 4 ml kg-1 min-1, range 40-80), exercised at 95 and 85% VO2, max to exhaustion (mean time = 14 +/- 3 and 31 +/- 8 min, expired ventilation (VE) over final minute of exercise = 149 +/- 9 and 126 +/- 10 l min-1). 2. Bilateral transcutaneous supramaximal phrenic nerve stimulation (BPNS) was performed before and immediately after exercise at four lung volumes, and 400 ms tetanic stimulations were performed at 10 and 20 Hz. The coefficients of variation of repeated measurements for the twitch transdiaphragm pressures (Pdi) were +/- 7-10% and for compound muscle action potentials (M wave) +/- 10-15%. 3. Following exercise at 95% of VO2, max, group mean Pdi twitch values were reduced at all lung volumes (range -8 +/- 3 to -32 +/- 5%) and tetanically stimulated Pdi values were reduced at both 10 and 20 Hz (-21 +/- 3 and -13 +/- 2%, respectively) (P = 0.001-0.047). Following exercise at 85% VO2, max, stimulated Pdi values were reduced at all lung volumes and stimulating frequencies, but only significantly so with the twitch at functional residual capacity (-15 +/- 5%). Stimulated Pdi values recovered partially by 30 min post exercise and almost completely by an average time of 70 min. 4. The fall in stimulated Pdi values post-exercise was significantly correlated with the percentage increase in diaphragmatic work (integral of Pdi min-1) from rest to end-exercise and the relative intensity of the exercise. 5. The integral of Pdi min-1 and the integral of Po min-1 (Po, esophageal pressure) rose together from rest through the fifth to tenth minute of exercise, after which integral of Pdi min-1 plateaued even though integral of Po min-1, VE and inspiratory flow rate all continued to rise substantially until exercise terminated. Thus, the relative contribution of the diaphragm to total respiratory motor output was progressively reduced with exercise duration. 6. We conclude that significant diaphragmatic fatigue is caused by the ventilatory requirements imposed by heavy endurance exercise in healthy persons with a variety of fitness levels. The magnitude of the fatigue and the likelihood of its occurrence increases as the relative intensity of the exercise exceeds 85% of VO2, max. PMID- 8487202 TI - Electrophysiology of guinea-pig supraoptic neurones: role of a hyperpolarization activated cation current in phasic firing. AB - 1. Immunocytochemically identified magnocellular neurosecretory cells (MNCs) in the guinea-pig supraoptic nucleus (SON) were studied using the in vitro intracellular recording technique. Cells were identified as containing arginine vasopressin (AVP) or oxytocin (OT) following recordings made with biocytin-filled electrodes. Both AVP and OT MNCs demonstrated a fusiform or pyramidal shape (15 20 microns by 26-39 microns), with two to three processes. There were no significant differences in the proportion of AVP and OT cells in the retrochiasmatic (caudal) versus the rostral slices. 2. No significant differences in passive membrane properties were observed between AVP and OT cells, except that AVP cells exhibited a significantly broader action potential width (1.51 +/- 0.1 ms, n = 11) than did OT cells (1.01 +/- 0.08 ms, n = 7). 3. Firing patterns were recorded for 100 MNCs, 41% of which fired in a phasic manner (repeated clustering of action potentials into bursts). Of the seventy-seven cells which were immunocytochemically identified, only AVP-containing MNCs displayed phasic firing. Phasic firing occurred only in MNCs demonstrating a depolarizing potential which followed hyperpolarizing after-potentials (HAPs). The presence of the depolarizing potential was not always associated with phasic firing, however, as both OT cells and non-phasic AVP cells sometimes exhibited a depolarizing potential. 4. In 160 MNCs examined for the presence of the time-dependent inward rectification (TDR in current clamp, or Ih in voltage clamp), a significant difference in the proportion of cells expressing the Ih was observed in the two cell types. The Ih was expressed in forty-five of fifty-four AVP MNCs (83%) and in six of fifteen OT MNCs (40%). No significant association was found with firing pattern. 5. The Ih exhibited properties similar to those found in other CNS and peripheral tissues. It appeared on steps to potentials more hyperpolarized than 65 mV. It was augmented by raising the extracellular potassium concentration, blocked by 2 mM CsCl, and insensitive to 100-500 microM BaCl2. Activation followed a single exponential, and the time constant of activation was voltage dependent. 6. The adenylate cyclase activator forskolin increased the Ih and shifted its activation curve to more depolarized levels. In cells recorded for several hours, the Ih varied in amplitude, suggesting intrinsic modulation, possibly by intracellular second messenger systems. The Ih in guinea-pig SON MNCs appears to serve an excitatory role, bringing cells closer to firing threshold. PMID- 8487203 TI - Energy metabolism in single human muscle fibres during intermittent contraction with occluded circulation. AB - 1. Glycogenolysis in type I and II muscle fibres was investigated in five healthy volunteers during electrical stimulation of the quadriceps muscle group with blood flow occluded. 2. The quadriceps femoris muscles were stimulated intermittently (1.6 s stimulation, 1.6 s rest) at a frequency of 50 Hz for 64 s and isometric contraction force was recorded. Muscle biopsies were obtained at rest prior to and immediately after stimulation. Single muscle fibres were dissected free and were identified as type I and II fibres. ATP, phosphocreatine (PCr) and glycogen contents were measured luminometrically and enzymatically in single fibres and mixed fibre muscle. 3. Electrical stimulation resulted in a marked decline in contraction force and near total depletion of PCr in both fibre types. The ATP turnover rate (P < 0.05) and the magnitude of the decline in ATP (P < 0.05) were greater in type II fibres. Prior to stimulation the muscle glycogen content was 32% higher in type II fibres compared with type I fibres (P < 0.01). During stimulation the rate of glycogenolysis in type II fibres (4.32 +/ 0.54 mmol (kg dry matter (DM)-1 s-1 was twofold greater than the rate in type I fibres (2.05 +/- 0.70 mmol (kg DM)-1 s-1, P < 0.05). 4. The data suggest that the relatively higher rate of glycogenolysis observed in type I fibres during intermittent electrical stimulation with occluded circulation (2.05 +/- 0.70 mmol (kg DM)-1 s-1), when compared with the corresponding rate recorded during intense contraction with circulation intact (0.18 +/- 0.14 mmol (kg DM)-1 s-1, P < 0.05), may result from an accelerated ATP turnover rate in this fibre type increasing the cellular concentrations of free AMP and inosine 5'-monophosphate (IMP), which are known activators of glycogen phosphorylase. 5. The similarity in the rate of type II fibre glycogenolysis during contraction with circulatory occlusion (4.32 +/- 0.54 mmol (kg DM)-1 s-1), when compared with the corresponding rate recorded during non-occluded circulation (3.54 +/- 0.53 mmol (kg DM)-1 s-1, P > 0.05), is in agreement with the suggestion that glycogenolysis in this fibre type is already occurring at a near-maximal rate with circulation intact. PMID- 8487204 TI - Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment. AB - 1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60% of maximum oxygen consumption rate (VO2) for 9-12 consecutive days at an ambient temperature of 40 degrees C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 degrees C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40 degrees C on the first and last day. 2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating. 3. Cardiac output increased significantly from the first to the final heat exposure from 19.6 to 21.4 l min-1; this was possibly due to an increased plasma volume and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone. 5. The exhaustion coincided with, or was elicited when, core temperature reached 39.7 +/- 0.15 degrees C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances. 6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress. PMID- 8487205 TI - Within-breath modulation of left ventricular function during normal breathing and positive-pressure ventilation in man. AB - 1. To investigate how intrathoracic pressure affects left ventricular function during normal breathing and positive-pressure ventilation, beat-by-beat measurements of left ventricular stroke volume (LVSV; pulsed Doppler ultrasound), heart rate and blood pressure were made in five normal subjects breathing actively and then undergoing passive positive-pressure ventilation. 2. To assess the within-breath effects of positive-pressure ventilation on left ventricular function in the clinical setting, further measurements were made in six patients sedated, paralysed and ventilated because of brain injuries, who had no disease of the heart or lungs. 3. In the normal subjects, there were minimal phasic variation in LVSV during positive-pressure ventilation with the subject passive. Heart rate and blood pressure also stayed relatively constant throughout the ventilator cycle. During active breathing at the same depth and rate, there were large phasic respiratory variations in LVSV, with the lowest values occurring during inspiration. 4. In the paralysed and unconscious patients, an increase in LVSV was associated with the increase in airway pressure which occurred during lung inflation; however, the phase lag between the rise in airway pressure and the rise in LVSV varied widely between patients. These changes occurred whether or not sinus arrhythmia was present. 5. Addition of 4.6 +/- 1 cmH2O of positive end-expiratory pressure (PEEP) did not increase the within-breath LVSV variations, but resulted in a mean depression of LVSV of 5.4% (paired t test, P = 0.035). 6. The smaller variations in LVSV during positive-pressure ventilation compared to normal breathing in the conscious subjects may reflect (a) the smaller magnitude of positive, compared to negative, pleural pressure excursions which accompany a given tidal volume, and (b) an asymmetry between the effects of positive and negative pleural pressure on the heart. 7. The prominent effects of positive-pressure ventilation on LVSV in unconscious patients, compared to the minimal effects seen in ventilated normal subjects, may result from reduced lung compliance and a degree of pulmonary vascular congestion in the patients which was undetectable clinically or radiologically. PMID- 8487206 TI - Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice. AB - 1. Single muscle fibres were enzymatically isolated from the soleus and extensor digitorum longus (EDL) muscles of genetically dystrophic mdx and normal (C57BL/10) mice aged 3-6 or 17-23 weeks. 2. Fibres of both muscles were chemically skinned with the non-ionic detergent Triton X-100 (2% v/v). Ca(2+)- and Sr(2+)-activated contractile responses were recorded and comparisons were made between several contractile parameters of various fibre types of normal and dystrophic mice of similar age. 3. There were no significant differences in the following contractile parameters of skinned fibres of normal and mdx mice of the same age: sensitivity to activating Ca2+ (pCa50) or Sr2+ (pSr50) and differential sensitivity to the activating ions (pCa50-pSr50). However the maximum isometric tension (Po) and the frequency of myofibrillar force oscillations in EDL fast twitch fibres of young mdx mice were significantly lower than those of soleus fast-twitch fibres of the same animals, or fast-twitch fibres (EDL or soleus) of normal mice. 4. Age-related differences were apparent in some contractile parameters of both normal and mdx mice. In particular the steepness of force-pCa and force-pSr curves increased with age in normal mice, yet decreased with age in fibres of mdx mice. 5. A fluorescent probe, ethidium bromide, which interchelates with DNA, was used with laser-scanning confocal microscopy to determine the distribution of myonuclei in fibres. Fibres isolated from either muscle type of normal animals displayed a characteristic peripheral spiral of myonuclei. Fibres from muscles of mdx mice displayed three major patterns of nuclear distribution; the normal peripheral spiral, long central strands of nuclei, and a mixture of these two patterns. 6. The contractile characteristics of mdx fibres were not markedly influenced by the nuclear distribution pattern in that there were no discernible differences in the major contractile parameters (the Hill coefficients nCa and nSr, which are associated with the steepness of the Ca2+ and Sr2+ activation curves, pCa50, pSr50, pCa50-pSr50) of skinned fibres possessing peripheral or central nuclei. However, except for nSr, these values were all lower in individual fibres which displayed similar proportions of central and peripheral nuclei. The presence of mixed nucleation and absence of fibres with embryonic contractile characteristics in mdx mice suggest that the dystrophin negative fibres can repair locally occurring muscle damage. PMID- 8487207 TI - Evidence from fluorescence microscopy and comparative studies that rat, ovine and bovine colonic crypts are absorptive. AB - 1. To test whether colonic crypts are secretory or absorptive interstitial [Na+] in rat descending colonic mucosa is determined using video-enhanced imaging of the impermeant acid form of the fluorescent Na+ probe SBFI (Molecular Probes) and intracellular [Na+] is monitored with SBFI (AM form). In rat descending colonic mucosa perifused with isotonic Tyrode solution interstitial [Na+] = 500-650 mM. Following exposure to Tyrode solution containing theophylline (10 mM) interstitial [Na+] falls by 300-450 mM within 1 min. Exposure to amiloride (0.2 mM) reduces the intracellular [Na+] from ca 25 to 12 mM within 15 min and concurrently decreases [Na+] in the interstitial fluid surrounding the crypts at the mucosal surface by approximately 200 mM. 2. The route of fluid inflow across the rat colonic mucosa is directly traced by perifusing with Tyrode solution containing the impermeant fluorescent dye, fluorescein disulphonate (FS). FS accumulates rapidly within crypt lumens of control tissues to a 2-fold higher concentration than in the external bathing solution, but FS does not accumulate in crypts of tissues treated with azide (2 mM). The increment in FS accumulation within the crypt lumen above the bulk solution decreases by 80% within 1 min following exposure to theophylline (10 mM), indicating that fluid absorption into crypts is reduced. Estimates of the total fluid influx from the rate and extent of FS concentration polarization within crypts indicate that it is sufficient to account for the entire transcolonic fluid absorption. 3. Comparative studies of isolated bovine and ovine colon were also undertaken to investigate the failure of bovine colon to generate a hypertonic absorbate and hence its incapacity to produce hard faeces. The interstitial fluid surrounding ovine colonic crypts is hypertonic to the bulk solution, whereas the interstitial fluid surrounding bovine colonic crypts is nearly isotonic with the bathing solution. Additionally, fluorescein disulphonate accumulates within ovine colonic crypt lumens by concentration polarization, whereas no concentration of FS occurs within bovine colonic crypt lumens. This corroborates the view that a hypertonic interstitial fluid is absent from bovine colon mainly because of a high rate of transepithelial leakage of low molecular weight solutes via paracellular routes. PMID- 8487208 TI - Asynchronous increases in oxidative capacity and resistance to fatigue of electrostimulated muscles of rat and rabbit. AB - 1. The present study investigates to what extent increases in resistance to fatigue and aerobic oxidative capacity of energy metabolism are correlated in fast-twitch tibialis anterior muscles of rat and rabbit subjected to chronic low frequency stimulation. 2. Changes in the aerobic oxidative capacity of the stimulated muscles were judged from increases in citrate synthase activity, representing the constant-proportion enzyme group of the citric acid cycle. 3. Resistance to fatigue reached maximal values in both rat and rabbit tibialis anterior muscles after stimulation periods of 14 days, whereas citrate synthase activity continued to increase with longer stimulation periods. 4. Different time courses of the changes in resistance to fatigue and citrate synthase activity were observed not only with prolonged stimulation periods but also during the first week, when pronounced increases in resistance to fatigue were accompanied by only moderate elevations in citrate synthase activity. 5. The dissociation between the changes of the two parameters studied suggests that factors other than elevated aerobic oxidative capacity contribute to enhanced resistance to fatigue. PMID- 8487209 TI - Tetrodotoxin-sensitive dendritic spiking and control of axonal firing in a lobster mechanoreceptor neurone. AB - 1. A primary mechanosensory neurone, the anterior gastric receptor (AGR) associated with gastric mill muscle in the lobster foregut was examined in vitro with extra- and intra-cellular recording techniques to understand processes of dendritic integration and dendro-axonal communication. 2. AGR has a 'T'-shaped geometry; its two long (> 3 mm) primary dendrites project distally to spatially separate, stretch sensitive terminals and converge centrally onto a common apical neurite that leads to a bipolar soma and single axon. 3. The receptor's bilateral dendrites are independently capable of generating action potentials. These appear to be Na+ dependent since they are blocked by tetrodotoxin, but not by Co2+ or a lack of Ca2+ in the bath saline. 4. Both dendrites are autogenically active, although impulses in the dendrite with the higher intrinsic excitability may cross over and activate the trigger zone on the contralateral side. Moreover, spikes arising on either dendrite do not actively invade the soma, but are conveyed as decremented potentials to a third trigger zone on the initial axon segment. 5. Focal applications of TTX (tetrodotoxin) demonstrated the existence and allowed precise definition of a central membrane compartment of AGR that appears to lack in functional Na+ channels. This inexcitable region includes the soma, the apical neurite and the central branch point of the two dendrites. A failure to observe collision block of bilateral dendritic potentials as they traverse the neurite supported this conclusion. 6. Horseradish peroxidase injections and staining revealed two morphological features of the apical neurite that differed markedly from other regions of the cell. In addition to a relatively large diameter, the neurite's plasma membrane is heavily convoluted and coiled to form a lamellar transverse profile. This latter feature may itself contribute to membrane inexcitability while the former is consistent with an elevated space constant for electrotonic conduction. 7. It is concluded that the inhomogeneous distribution of membrane excitability in AGR enhances the integrative capability of the receptor's dendrites, permitting mechanical input at diverse loci to be encoded and processed prior to transformation into axonal discharge. PMID- 8487210 TI - Effects of specific carotid body and brain hypoxia on respiratory muscle control in the awake goat. AB - 1. We assessed the effects of specific brain hypoxia on the control of inspiratory and expiratory muscle electromyographic (EMG) activities in response to specific carotid body hypoxia in seven awake goats. We used an isolated carotid body perfusion technique that permitted specific, physiological, steady state stimulation of the carotid bodies or maintenance of normoxia and normocapnia at the carotid bodies while varying the level of systemic, and therefore, brain oxygenation. 2. Isolated brain normocapnic hypoxia of up to 1.5 h duration increased inspired minute ventilation (VI) by means of increases in both tidal volume (VT) and respiratory frequency (fR). Electromyographic activities of both inspiratory and expiratory muscles were augmented as well. These responses were similar to those produced by low levels of whole-body normoxic hypercapnia. We conclude that moderate levels of brain hypoxia (Pa,O2 approximately 40 mmHg) in awake goats caused a net stimulation of ventilatory motor output. 3. Hypoxic stimulation of the carotid bodies alone caused comparable increases in VT and fR, and EMG augmentation of both inspiratory and expiratory muscles whether the brain was hypoxic or normoxic. These responses were quite similar to those obtained over a wide range of whole-body normoxic hypercapnia. We conclude that the integration of carotid body afferent information is not affected by moderate brain hypoxia in awake goats. 4. We found no evidence for an asymmetrical recruitment pattern of inspiratory vs. expiratory muscles in response to carotid body hypoxia or in response to brain hypoxia alone. 5. Our data support the concept that moderate brain hypoxia results in a net stimulation of respiratory motor output. These findings question the significance of 'central hypoxic depression' to the regulation of breathing under physiological levels of hypoxaemia in the awake animal. PMID- 8487211 TI - Fluctuations in blood flow to acral skin in humans: connection with heart rate and blood pressure variability. AB - 1. Spontaneous fluctuations in blood flow in arteries supplying acral skin were investigated with Doppler ultrasound in human subjects. Finger blood pressure, heart rate (HR) and cardiac output were measured simultaneously and noninvasively. 2. Synchronous fluctuations in flow were found in arteries supplying the hands and feet. The fluctuations were larger and more rapid than the flow variations which have been demonstrated with other methods. The magnitude of the total flow fluctuations in the hands and feet was estimated to be 5-10% of cardiac output in resting subjects. This range of flow fluctuations is made possible by spontaneous opening and closing of skin arteriovenous anastomoses (AVAs). 3. The fluctuations in skin blood flow were accompanied by inverse fluctuations in mean blood pressure (MAP). The power spectra of skin vascular conductance and MAP both contained maximum intensity at low frequencies, below 0.15 Hz, with high coherence. 4. The central circulatory events connected with the skin blood flow fluctuations were calculated from the experimental data with the use of transfer function analysis. There was a rise in HR, cardiac output and MAP starting 1-4 s before a cutaneous vasoconstriction. This indicates that the HR and MAP responses are not only passive effects of changes in peripheral resistance, but are the result of a simultaneous activation of the peripheral vascular and cardiac efferent branches of the autonomic nervous system. The HR and MAP responses are then modified, probably by baroreceptor activation. PMID- 8487212 TI - Incidence of non-driving excitation of Ia afferents during ramp frequency stimulation of static gamma-axons in cat hindlimbs. AB - 1. The aim of this investigation was to identify static gamma-axons which do not drive any Ia afferents at any stimulus frequency in any spindle which they supply, and to determine their occurrence in various hindlimb muscles (peroneus tertius, brevis, longus and tenuissimus). 2. Ia responses to static gamma stimulation were classified as 'non-driven' when the discharge did not follow the stimulation frequency, or its subharmonics, at any time during a linear increase in stimulus frequency up to 150 Hz lasting 2-3 s, and when tested at two muscle lengths--except in the tenuissimus muscle. In almost all experiments, cross correlograms were used in addition to evaluate the percentage of these 'non driven' responses in which a time-locking of discharge to stimulus pulses was obscured by irregularity of the Ia discharge. 3. In 104 spindles, out of 347 responses to stimulation of single static gamma-axons 332 (93%) could be characterized, and of these, 57% (183) were of the non-driven type. The mean number of static gamma effects characterized per spindle was 4.1 (fourteen experiments). In the large majority of spindles (79%, 82 out of 104) at least one response was of the non-driven type. 4. Of the static gamma-axons studied 16% were called 'non driving' ('ndr' gamma s-axons) because they elicited non-driven effects, and since they had the same qualitative effect consistently in all spindles whose discharge was modulated by stimulating them they were called specific 'ndr' axons. If axons with non-driven effects, but acting on one spindle were included in the 'non-driving' category the proportion was 23%. Of spindles tested 63% were innervated by at least one 'ndr' axon. 5. Absence of Ia driving during ramp frequency stimulation of gamma s-axons has been equated with selective bag2 contraction. All the non-driven responses identified in this study cannot be attributed to exclusive bag2 involvement because the total number of 'ndr' responses was too high. In fact, in the isolated spindle preparation bag2 and chain co-contraction were shown to elicit non-driven responses, so chain contraction is not detected reliably in all experimental conditions. Possibly chain fibre contraction is sometimes too weak to dominate the response, or can be of a non-driving character.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487213 TI - Involvement of intrahepatic innervation in caesium-induced haemodynamic oscillations in the rat liver. AB - 1. Cs+ was used to study the mechanisms involved in the induction of haemodynamic and metabolic oscillations in the isolated rat liver perfused by the portal vein. 2. Cs+ (2.25 mM) in K(+)-free perfusate causes the appearance of periodic increases in portal pressure (3.87 +/- 0.6 mmHg, n = 24) and decreases in O2 uptake (111 +/- 26 microM) at a frequency of 0.013 +/- 0.002 Hz. A 19.8 +/- 1.2 min induction time occurs prior to the generation of periodicity. The oscillations are interspersed with low amplitude shoulders and peaks indicating multiple non-phasic components. 3. Cs+ concentrations higher or lower than 2.25 mM decrease oscillation amplitude and render them aperiodic. No oscillations are observed with 0.5 or 12.5 mM Cs+. 4. The oscillations are reversibly blocked by 1 mM K+, 1 mM EGTA, 5 microM verapamil or 0.17 microM tetrodotoxin. One micromolar chlorpheniramine, 10 microM propranolol, 12 microM phentolamine or 35 microM atropine also maximally inhibit the Cs(+)-induced vasoactivity. 5. The results show that the liver perfused by the portal vein has all of the components required to activate vascular synchrony including intrinsic neural input and responsive vasoactive cells. PMID- 8487214 TI - The time course of phosphate metabolites and intracellular pH using 31P NMR compared to recovery heat in rat soleus muscle. AB - 1. The recovery time course of changes in phosphate metabolites and pH, after tetanic contractions of 6 and 9 s were studied using 31P NMR with 4 and 16 s resolution, in rat soleus muscles at 20 degrees C. Muscles were at a sarcomere length of 3.15 microns (active), being greater than optimum for force which was 2.88 microns (active). 2. The post-contraction recovery of chemical changes was compared with the heat production in parallel experiments. Initial and recovery heat production were measured in tetanically stimulated muscles. 3. During recovery from tetanic contractions the changes in phosphocreatine (PCr) matched the changes in inorganic phosphate (Pi). The change in intracellular pH (pHi) was biphasic. The pHi first became more alkaline after contraction and then decreased until it reached a point below the baseline value. There was then a final recovery. 4. The initial heat and recovery heat production were greater than that expected from the PCr hydrolysis estimated during the tetanus and the PCr resynthesis that follows. 5. These data support the presence of 'unexplained heat' during a contraction and its related recovery processes in rat soleus muscle. PMID- 8487215 TI - Membrane properties and synaptic potentials of three types of neurone in rat lateral amygdala. AB - 1. Intracellular recordings were made from the lateral nucleus of the amygdala in tissue slices cut from rat brain and maintained in vitro. 2. Three types of neurones were distinguished according to the after-potential that followed an action potential. Type 1 cells (44%, n = 225) had depolarizing after-potentials, resulting from a calcium-dependent chloride conductance. Type 2 cells (48%) had long-lasting (> 250 ms) hyperpolarizing after-potentials and type 3 cells (8%) had shorter hyperpolarizing after-potentials. The average resting potentials of the three cell types were -78, -69 and -62 mV respectively. Intracellular labelling with biocytin showed that type 1 cells were pyramidal neurones; type 2 and type 3 cells were non-pyramidal. 3. Experiments with receptor antagonists identified synaptic potentials mediated by excitatory amino acids and by GABA (acting at GABAA receptors) in all three cell types. A longer duration inhibitory synaptic potential resulting from activation of GABAB receptors was present in type 1 (pyramidal) and type 2 cells. 4. Cholecystokinin (100 nM to 1 microM) depolarized type 2 and type 3 cells but had no effect on type 1 (pyramidal) cells. Baclofen (1-3 microM) hyperpolarized type 1 and type 2, but not type 3 cells. [Met5]enkephalin (1-10 microM) hyperpolarized only type 2 cells. 5. It is concluded that the lateral nucleus of the amygdala contains pyramidal neurones and two types of non-pyramidal neurone; these can be differentiated by membrane properties, synaptic inputs and sensitivities to transmitters. PMID- 8487216 TI - Relaxant innervation of the guinea-pig trachealis: demonstration of capsaicin sensitive and -insensitive vagal pathways. AB - 1. The guinea-pig trachea was isolated with its extrinsic innervation intact and placed in a water-jacketed dissecting dish containing warmed, oxygenated Krebs solution. The trachea was not separated from the oesophagus. Two adjacent cartilage rings of the rostral portion of the trachea were cut open opposite the trachealis and prepared for isometric tension measurements. 2. Following the addition of atropine and contraction of the trachealis with prostaglandin F2 alpha (PGF2 alpha), stimulation of the cervical sympathetic trunks elicited relaxations that were abolished by propranolol or hexamethonium. Stimulation of the vagus nerves caudal to the nodose ganglia also elicited relaxations. These vagally mediated relaxations were unaffected by propranolol but were abolished by hexamethonium or by cutting the recurrent laryngeal nerves. 3. After cutting the vagi caudal to the nodose ganglia, stimulation of the vagi rostral to the nodose ganglia elicited relaxations of the trachealis that were not significantly affected by either propranolol or hexamethonium but were abolished by cutting the superior laryngeal nerves. Stimulation of right vagi which had undergone supranodose vagotomy 14 days prior to experimentation was without effect on the smooth muscle of the guinea-pig trachea while the response to stimulation of the left vagus was unchanged. 4. Acute capsaicin desensitization abolished relaxations of the guinea-pig trachealis elicited by stimulation of the vagal fibres carried by the superior laryngeal nerves. In contrast, capsaicin desensitization only modestly inhibited relaxations elicited by stimulation of the preganglionic parasympathetic fibres carried by the recurrent laryngeal nerves and had no effect on sympathetic nerve-induced relaxations. 5. Removing the oesophagus selectively abolished relaxations elicited by stimulation of both vagal pathways of non-adrenergic relaxant innervation. Non-adrenergic relaxations of the trachealis elicited by electrical field stimulation were unaffected by removing the oesophagus. Oesophagus removal also had no effect on the parasympathetic-cholinergic contractile innervation or the sympathetic relaxant innervation of the trachealis. 6. The results indicate that the guinea-pig trachealis receives non-adrenergic relaxant innervation from both parasympathetic and capsaicin-sensitive vagal pathways. The results also suggest that the neurones mediating non-adrenergic relaxations of the trachea are sensitive to oesophagus removal. The observation that oesophagus removal abolishes parasympathetic relaxations of the trachealis while having no effect on parasympathetic contractions supports the hypothesis that the guinea-pig trachealis receives excitatory and inhibitory innervation from distinct vagal parasympathetic pathways. PMID- 8487217 TI - Orofacial manifestations in primary immunodeficiencies involving IgA deficiency. AB - The orofacial manifestations of 39 patients with primary IgA deficiency are reported. Aphthous-like oral ulceration was observed in 61% while candidosis and recurrent herpes labialis were each present in 25%. Only 4 (9%) patients had no orofacial lesions. PMID- 8487218 TI - Clonal expansion of lymphocytes from oral lichen planus lesions. AB - Lymphocytes were extracted from 11 biopsy specimens of oral lichen planus (OLP) by collagenase digestion, and cell lines were expanded with repetitive cycles of stimulation (with phytohaemagglutinin) and rest in media supplemented with interleukin 2. Four OLP lines contained a majority of CD3+CD4-CD8+ cells, in six lines the CD4:CD8 ratio was between 1 and 2, and in one line the CD4:CD8 ratio was 5:1. Limiting dilution of nine lines at 0.3 and 1.0 cells/well resulted in viable wells (putative clones) with plating efficiencies ranging from 0.0 to 18.1 percent and 0.0 to 22.2 percent respectively. The majority of clones were CD3+CD4 CD8+alpha beta+gamma delta-, although three clones were CD3+CD4+CD8-alpha beta+gamma delta- and one clone was CD3+CD4-CD8- and expressed the gamma delta T cell receptor. T cell clones derived from lymphocytes extracted from OLP lesions may be generated and maintained in culture providing opportunity for their further phenotypic and functional characterisation. This strategy may facilitate the identification of a putative oral lichen planus-specific antigen and indicate the frequency of lichen planus-specific T cells within lesions of OLP. PMID- 8487219 TI - Role of thermal trauma in experimental oral mucosal Candida infections in rats. AB - A model of candidosis in experimental rats was used to study the role of trauma in the aetiology of oral mucosal infections caused by Candida albicans. Standardised thermal trauma was delivered to the dorsum of the tongue of Sprague Dawley rats and experimental candidosis was induced. Histologically, the site of trauma was invaded by hyphae earlier and more extensively than in control animals, leading to the conclusion that trauma facilitated the establishment of the C. albicans infections. PMID- 8487220 TI - Effect of sialoadenectomy on the carriage of Candida albicans in the mouths of rats. AB - Xerostomia provoked in rats by surgical removal of the major salivary glands significantly increased oral carriage of Candida albicans. Five weeks after 3 oral inoculations of 10(8) CFU, C. albicans were found in the mouths in 50% of normal animals but after 8 weeks in none. In xerostomic rats, 100% had oral C. albicans after 5 weeks and after 18 weeks, 66.6% still harboured yeasts. Over the whole experimental period the amount of C. albicans was greater in the mouths of sialoadenectomized than in normal rats. PMID- 8487221 TI - Legume-associated residual cyst. AB - This report describes three unique cases of residual cyst (RC) which were characterized by large legume implants. To determine whether these represented a distinctive RC subset or if implanted materials have general importance in RC pathogenesis, a retrospective comparison of these cases and 37 further RCs with 40 control periapical cysts was performed. The frequency of foreign material implantation and the associated histopathologic features were assessed. No significant differences were noted suggesting that foreign implantations do not have an etiologically significant association with RCs and that the legume associated RCs represent a unique subgroup. The relationship of the legume associated RCs to the category of lesions variously termed giant cell hyaline angiopathy, oral pulse granuloma or hyaline ring granuloma is discussed. PMID- 8487222 TI - Hospital psychiatric units. Nonsmoking policies. AB - Establishing nonsmoking policies in hospitals--even on acute psychiatric units- requires patience, planning, and a bit of nerve. The benefits of such a move, however, can be significant for patients and staff. When Vancouver General Hospital implemented a complete indoor nonsmoking policy on its psychiatric assessment and inpatient psychiatry units, workplace conditions noticeably improved, and some long-standing beliefs about psychiatric patients were disproved. Several conditions provided the impetus to change to a nonsmoking policy. With a few exceptions (palliative care, the burn unit) the indoor areas were nonsmoking; nevertheless, the hospital environmental committee considered a site-wide (indoor and outdoor) ban on smoking. One reason was that the community funding that had provided psychiatric patients with cigarettes would soon be cut off. Another reason was that all psychiatry units were anticipating moving into the new hospital tower--a facility slated to be smoke-free--on its completion. PMID- 8487223 TI - Lesbian self-disclosure. Strategies for success. AB - 1. Lesbian nurses must decide whether to share information about lesbian culture with their nursing colleagues. 2. Making calm rejoinders to homophobic remarks, using policies on minority status and affirmative action, promoting competitive liberalism between institutions, and using marketing techniques can aid lesbian self-disclosure to individuals and institutions. 3. Nurses who are open about being lesbian can provide healthy role models for their colleagues and patients. PMID- 8487224 TI - Partnership to prevent chemical dependency in nursing using Neuman's systems model. AB - 1. Neuman's theory of optimal client system, which has the goal to maintain or to bring about the system's stability by the process of reconstitution, is used as the basis for the prevention efforts of the West Tennessee Nurses' Peer Assistance Program. Efforts are directed at bringing the client system to a state of stability or wellness that is higher than the previous state of chemical dependency. 2. The program has grown in both number of clients and in comprehensiveness of its prevention activities. Prevention in three specific areas--primary, secondary, and tertiary--is needed to combat the chemical dependency problem in nursing. 3. A continued partnership between the university, the school of nursing, the TNF, the TBN, and the various health care providers and nurse practitioners is needed to address the problem of chemical dependency in nursing. PMID- 8487225 TI - Focus on dementia. PMID- 8487226 TI - Relationships between cognitively impaired elders. PMID- 8487227 TI - What goals and interventions are important for psychiatric nurses to use when working with homeless chronically mentally ill? PMID- 8487228 TI - Clozapine: how it changed my life. PMID- 8487229 TI - More violence, more need for change. PMID- 8487230 TI - Recovering our sense of value after being labeled mentally ill. AB - 1. People with mental illness must know that mental illness does not mean they can no longer lead full lives. Role models--successful people who have mental illness--are needed. 2. There is a great danger in labeling a person as an illness. Once people believe they are an illness, there is no one left inside to take a stand toward the illness; they give up control and others take responsibility for them. 3. "High functioning" and "low functioning" are not attributes that exist inside a person. They are value judgments that are put on a person. There are no high-functioning or low-functioning people. There are people whose contribution we are able to see and value and there are those whose gifts we have failed to see and have failed to value. PMID- 8487231 TI - Local anesthesia for cryosurgery on the cervix. AB - Forty-five patients were evaluated in a prospective, randomized study to determine the effectiveness of a local injection of lidocaine in reducing pain during cervical cryosurgery. Study patients received a submucosal cervical injection of 1% lidocaine with a 1:100,000 dilution of epinephrine. Control patients did not receive an injection. Both groups received a single dose of naproxen sodium or ketoprofen prior to the procedure. The patient and the observing nurse recorded the pain experienced with a visual analog scale (VAS). Nurse and patient response for the control and study groups showed a high correlation (r = .573 and P < .01, r = .673 and P < .001, respectively). The mean VAS score recorded for the 26 control patients was 4.27, significantly greater than the mean score for the 19 study patients, 1.16 (P < .001). These findings indicate that a submucosal local injection of lidocaine with epinephrine is effective in reducing pain during cervical cryosurgery. PMID- 8487232 TI - LA-1 oncogene. A possible new prognostic index for evaluating cervical squamous intraepithelial lesions. AB - Cervical biopsies from 96 patients referred to the Union Memorial Hospital Colposcopy Clinic were analyzed for the expression of the LA-1 oncogene by using an antibody directed against a 13 amino acid epitope of the oncogene product. The expression of the oncogene was found to correlate with the grade of the cervical intraepithelial lesion. A trend was suggested even though chi 2 analysis was not significant (P = .08). Further studies are warranted to determine whether the LA 1 test predicts persistence or progression of the disease. PMID- 8487233 TI - Estrogen replacement therapy and breast cancer. AB - The safety of estrogen use in breast cancer patients is discussed. Most reports indicate there is no risk. PMID- 8487234 TI - Elective cesarean hysterectomy for treatment of cervical neoplasia. An update. AB - From January 1, 1979, to March 31, 1991, 37 patients underwent elective cesarean hysterectomy for early cervical neoplasia. Thirty-four patients had cervical intraepithelial neoplasia III, and three patients had stage IA-1 squamous cell carcinoma of the cervix. Twenty-eight were primary cesarean sections; nine had obstetric indications. The mean operative time was 128 minutes; mean estimated blood loss was 1,400 mL. One patient experienced an intraoperative hemorrhage (3,500 mL). There were no other recognized intraoperative complications. Four significant postoperative complications included a vaginal cuff abscess, a wound dehiscence and pelvic abscess, one patient with febrile morbidity and an ileus and ligation with partial transection of a ureter. Patients were discharged on a mean of postoperative day 5.7. Although significant complications occurred, we believe that the noncompliant nature of our patient population justifies elective cesarean hysterectomy for treatment of cervical neoplasia. PMID- 8487235 TI - Maternal renal artery Doppler flow-velocity waveform in preeclampsia. A preliminary report. AB - By use of duplex Doppler ultrasonography, we preliminarily studied 30 normal pregnancies (control group) and 30 patients with preeclampsia (study group) before treatment. The peak systolic flow height to end diastolic flow height (S/D) ratio of the maternal right and left renal arteries of both groups were compared and analyzed. The results showed that there were no significant differences between the right and left renal arteries in either group, but unexpectedly the S/D ratio of the renal artery on both sides in preeclamptic patients was significantly lower than in normal pregnant women (mean +/- SD, 2.07 +/- .12 vs. 2.41 +/- .12, respectively, P < .001). The lower S/D ratio of the renal artery may reflect a decrease in renovascular resistance and an increase in renal perfusion. These findings were the reverse of what might be expected from an elevated vascular resistance and hypoperfusion model. PMID- 8487236 TI - Breech presentation and fetal growth retardation. AB - Although it has been consistently demonstrated that breech presentation is associated with fetal growth retardation, this relationship has not been clarified. This study intends to elucidate this association by use of live births recorded in North Carolina in 1988 and 1989. A remarkable difference in birth weight between breech and vertex infants existed only in the preterm births. Although the breech infants had a higher proportion of small for gestational age than the vertex infants, the difference in the proportions decreased with advancing gestational age. Our analysis indicated that breech presentation is unlikely to be a cause of fetal growth retardation. Results of the study also implied that the significant association between breech presentation and increased perinatal mortality may be due in part to the common correlation with premature delivery and fetal growth retardation. PMID- 8487237 TI - Tuboovarian abscesses after operative hysteroscopy. AB - Postoperative infection after operative hysteroscopy is uncommon. However, patients who have a past history of pelvic inflammatory disease appear to be at risk of developing such infections, including tuboovarian abscesses. Prophylactic antibiotics during operative hysteroscopy appear to be effective in preventing this problem. PMID- 8487238 TI - Fetal biparietal diameter, head circumference, abdominal circumference and femur length. A comparison by race and sex. AB - Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL) were compared by race and sex in 5,405 ultrasound examinations done on 2,831 women. Black fetuses had significantly longer FL than white fetuses; male fetuses had larger BPD, HC and AC than females. The differences in BPD, HC and AC correlated with the different birth weights observed between male and female infants, 3,253 vs. 3,153 g. The difference in birth weight between black and white infants, 3,152 vs. 3,331 g, did not correlate with differences in their respective BPD, HC and AC. Earlier delivery accounted for some but not all of the birth weight difference between black and white infants. Our data suggest that there may be differences in body length proportions (longer legs and shorter trunks in black infants) that are important factors in understanding the birth weight difference between black and white infants. Furthermore, fetal race and sex differences could account for some degree of error in the ultrasound estimation of gestational age. PMID- 8487239 TI - Evaluation of low-dose estrogen and progestin therapy in postmenopausal women. A double-blind, prospective study of sequential versus continuous therapy. AB - In this prospective, double-blind study, we evaluated the efficacy and safety of low-dose estrogen and progestin replacement therapy in 36 postmenopausal women who were administered oral medroxyprogesterone acetate (MPA) cyclically or continuously in combination with conjugated equine estrogen (CEE) 0.625 mg daily. In the sequential group, MPA (5.0 mg) was administered daily for 12 days of each 25-day treatment cycle. In the two continuous groups, MPA was administered without interruption at a daily dose of either 2.5 mg or 5.0 mg for 12 treatment cycles. Of the 36 women in the study, 29 women completed the one-year protocol. The clinical and metabolic responses were assessed before and every three cycles during the 12 cycles of treatment. Endometrial biopsies and lumbar bone density scans were performed before and during the last week of the 12th treatment cycle. Vasomotor and urogenital symptoms improved in all women. Cyclic menstrual bleeding occurred in all patients on sequential therapy, and proliferative endometrium was noted in two of these women. All patients in both continuous treatment groups experienced amenorrhea after the fifth cycle of therapy, and all endometrial biopsies were atrophic or inactive. From the 3rd through the 12th month of cycle, favorable lipid and lipoprotein changes occurred in all treatment groups. Lumbar bone mineral density improved significantly (P < .05) by an average of 6.41% in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487240 TI - Weight, length, head and chest circumference at birth in Phoenix, Arizona. AB - Standard percentile curves are presented for weight, length, head circumference and chest circumference at birth for a population of 27,963 singleton infants born between the gestational ages of 26 and 42 weeks at a large, private hospital in Phoenix, Arizona. At term, all four growth parameters were significantly greater in male than in female infants. These parameters were significantly reduced in infants born to mothers who smoked and increased in infants born to mothers with diabetes. Percentiles in all parameters were higher than in those of previous studies, suggesting that continued use of growth curves based on older data may result in misclassification of infants with respect to appropriateness of growth-for-gestational age. PMID- 8487241 TI - Subtle ultrasound signs of appendicitis in a pregnant patient. A case report. AB - An abnormal, 1 cm in diameter appendix in a pregnant patient was demonstrated using graded compression sonography. Prior to the use of this technique, the suggestion of appendicitis on ultrasound examination was made only after observation of an abscess or peritoneal fluid. PMID- 8487242 TI - Prenatal diagnosis of fetal pelvic kidney. A case report. AB - Published experience on prenatal diagnosis of pelvic kidney is limited. We present the ultrasonographic characteristics of a case of ectopic pelvic kidney and discuss the significance of prenatal diagnosis. PMID- 8487243 TI - Management of osteogenesis imperfecta in pregnancy. A case report. AB - Osteogenesis imperfecta (OI) is a metabolic disorder of connective tissue; it is typically characterized by blue sclera, bone fragility and deformity secondary to repetitive fractures. The severity of the disease in the infant cannot be predicted by the phenotypic presentation of the mother. We present a case report and review literature and discuss the prenatal diagnosis, evaluation criteria and guidelines for delivery. PMID- 8487244 TI - Spontaneous uterine rupture after hysteroscopic metroplasty with uterine perforation. A case report. AB - This is the first documented case of spontaneous uterine rupture during pregnancy following hysteroscopic metroplasty complicated by uterine perforation. This case emphasizes the importance of treating these patients as high risk throughout pregnancy. PMID- 8487245 TI - Preclinical and clinical pharmacology of carvedilol. AB - Carvedilol is a novel multiple-action cardiovascular drug that has recently been introduced to the market for the treatment of mild to moderate hypertension. Clinical studies have demonstrated that once daily therapy with carvedilol is efficacious and has a favourable side-effect profile. Clinical studies are in progress to establish the utility of carvedilol in angina and congestive heart failure. Carvedilol is a beta-adrenoceptor antagonist and a vasodilator, with the vasodilating activity resulting primarily from alpha 1-adrenoceptor blockade and possibly also from calcium channel blockade. The reduction in BP produced by carvedilol results from the vasodilating activity of the drug because peripheral vascular resistance is significantly reduced. The reduction in BP produced by carvedilol is not associated with reflex tachycardia owing to the beta adrenoceptor blocking activity of the compound. Throughout its antihypertensive dose range, carvedilol has been a renal-sparing antihypertensive agent in animals and also in humans, inasmuch as renal blood flow, glomerular filtration rate and sodium excretion are all maintained. In preclinical experimental models of acute myocardial infarction, carvedilol has produced marked reductions in infarct size in the pig, rat and dog. The cardioprotection observed with carvedilol is greater than that provided by beta-adrenoceptor antagonists alone, suggesting that the additional activities of carvedilol may provide benefit in the setting of myocardial ischaemia. PMID- 8487246 TI - Relationship between cardiovascular haemodynamics and goals of antihypertensive therapy. AB - Hypertension is a haemodynamic disorder, reflecting a disturbance in the ratio between cardiac output and total peripheral resistance. In nearly all forms of established hypertension, total peripheral resistance is increased and cardiac output is abnormally low, particularly during exercise. When left untreated, total peripheral resistance increases, cardiac output falls and BP increases over time. The coronary reserve is reduced. Antihypertensive agents affect central haemodynamics differently. Vasodilators like alpha-blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors all reduce total peripheral resistance and maintain cardiac output unchanged at rest as well as during exercise. In contrast, beta-blockers do not usually reduce total peripheral resistance much below the pretreatment level, and cardiac output is chronically depressed, particularly during exercise. However, the beta-blockers greatly reduce the workload in the heart by decreasing the rate-pressure product. Recently-developed beta-blockers with vasodilating activity, such as carvedilol, are based on a combination of beta-blockade and vasodilatation. Such beta blockers also induce marked reduction in pressure-rate product and some reduction in total peripheral resistance. They induce less reduction in cardiac output during exercise than ordinary beta-blockers. From a theoretical point of view, this type of antihypertensive treatment should maintain good BP control, reduce cardiac workload and be associated with fewer side-effects than ordinary beta blockers. PMID- 8487247 TI - Altered coronary flow reserve in the hypertrophied heart: implications for therapy. AB - Coronary flow reserve has been shown to be abnormally low in several models of left ventricular hypertrophy induced by long-standing pressure overload. Because the presence of hypertrophy is a risk factor for the development of subendocardial ischaemia and sudden death, efforts to restore alterations in flow reserve may prove beneficial. In the following review, we discuss potential mechanisms which might contribute to this abnormal vasodilator capacity in the hypertrophied heart, with particular emphasis on how chronic therapy may potentially reverse such abnormalities. In addition, we report how the acute administration of various classes of pharmacological agents can alter measurements of coronary flow reserve, as observed in our anaesthetised swine model. Such factors must be considered before interpreting any changes in coronary flow reserve in models of hypertrophy following chronic administration of drugs. PMID- 8487248 TI - Kidney and aetiology, pathology and management of essential hypertension. AB - The existence of a relationship between the kidney and arterial hypertension has long been known. Renal participation in the development of arterial hypertension has been clearly shown in different animal models that mimic human essential hypertension. Some data obtained in hypertensive humans also seem to support the prevalence of the kidney in the initiation of this particular type of arterial hypertension. On the other hand, renal vasculature can also suffer the consequences of essential hypertension and, as a result, chronic renal failure can develop. The role of antihypertensive therapy in preventing renal damage has been sufficiently addressed. However, investigation of the potential for facilitating the antihypertensive capacity of drugs through their renal effects and investigation of the differing abilities of particular groups of antihypertensive agents to prevent or slow the progression of renal damage constitutes a challenge for future research. PMID- 8487249 TI - Renal haemodynamics in hypertension: effects of antihypertensive drugs. AB - Sustained essential hypertension is characterised by a progressive decline in renal blood flow and a progressive increase in renal vascular resistance, while glomerular filtration rate remains normal or is reduced to a lesser extent. Renal blood flow is not only decreased per unit square metre of body surface area but also as a fraction of cardiac output. Although the precise mechanism of this renal haemodynamic abnormality remains speculative, the possibility that the renal vasculature plays a role in the pathogenesis of essential hypertension is receiving major attention. Different antihypertensive drugs have different renal haemodynamic effects. Nonselective beta-blockers generally tend to cause a modest decrease in renal blood flow but certain beta-blockers (including those with cardio-selectivity or intrinsic sympathomimetic activity) appear to cause less of a reduction in renal haemodynamics than others. Adrenergic blocking agents and diuretics do not produce clinically relevant renal haemodynamic changes, and data obtained with vasodilators are conflicting. Most studies with calcium antagonists show a renal vasodilator response. Angiotensin-converting enzyme inhibitors increase renal blood flow and decrease renovascular resistance in essential hypertension. PMID- 8487250 TI - The issue of quality of life in antihypertensive therapy. AB - The treatment of hypertension is based on an assessment of the balance between the effects of therapy on survival on the one hand and effects of the patient's symptoms and well-being on the other. The concept of quality of life is used to summarise the latter effects. Preservation of quality of life involves both the prevention of hypertensive complications and detrimental effects on well-being induced by drugs. However, scientific accumulation of data in this area has been severely hampered by the lack of consensus as to how quality of life should be defined and measured. The scientific power of the quality of life concept has also yet to be proven. Although recent studies indicate that specific aspects of quality of life could be adequately assessed the relative importance of minor shifts in questionnaire or test scores remains an unresolved scientific and clinical issue. Despite these shortcomings a series of studies now available suggests that there are only minor differences between the first-line antihypertensive drugs (e.g. beta-blockers and ACE inhibitors) regarding their effect on quality of life. PMID- 8487251 TI - Clinical significance of the metabolic effects of antihypertensive drugs. AB - Data from the Hypertension Treatment Trials do not indicate that the metabolic effects of the medications used, namely diuretics in all and beta-blockers in some, are of great clinical significance. Effects on lipids are mainly short-term (about one year) and the increased incidence of significant hyperglycaemia and/or diabetes in treated compared with control or placebo subjects is < 1% in most trials. The use of these drugs has improved the prognosis of subjects with both severe and less severe hypertension. Despite these findings, it is possible that medications such as the calcium blockers, ACE inhibitors, or multiple-action drugs, e.g. the alpha-beta-blockers which have no negative and possibly have some positive effects on lipids and glucose metabolism, will improve outcome still further. We must await additional long-term trials to determine this. It is possible that combinations of small doses of two different agents from different classes of drugs will prove to be the ideal approach to hypertension management in the future: efficacy is improved and any adverse metabolic effects are minimised. PMID- 8487252 TI - Treating hypertension in the elderly. AB - Hypertension is a common problem in the elderly, with a prevalence of about 50%. The risk of cardiovascular disease and death is increased in hypertensive patients aged 60-79 years, whereas this increased risk seems to be diminished or even non-existent in those aged > or = 80 years. Antihypertensive drug treatment has been shown to be beneficial for most elderly patients but whether this is also true for the oldest patients is less clear. Treatment is more difficult in the elderly than in the middle aged or young because of the structural and functional alterations of the cardiovascular system associated with ageing (in particular the impairment of BP homeostasis), which contraindicate some drugs and impose a cautious use of the remaining ones. Isolated systolic hypertension increases the cardiovascular risk but we lack data on the efficacy of treatment in this group. PMID- 8487253 TI - Fluorine-18-labeled progestin ketals: synthesis and target tissue uptake selectivity of potential imaging agents for receptor-positive breast tumors. AB - We have studied two new fluorine-substituted progestins as potential imaging agents for progesterone-receptor-positive human breast tumors. The steroids are 16 alpha, 17 alpha-fluoroacetophenone ketals of 16 alpha, 17 alpha dihydroxyprogesterone and 16 alpha, 17 alpha, 21-trihydroxy-19-norprogesterone. Synthesis of the latter compound in seven steps from 19-norandrost-4-ene-3,17 dione is reported. Both compounds demonstrate high affinity for the progesterone receptor (PgR) (52.5 and 240%, respectively, relative to R5020 = 100). The syntheses were adapted to 18F-labeling with 4'-[18F]-fluoroacetophenone, prepared from 4'-nitroacetophenone by nucleophilic substitution with K18F/Kryptofix. Considerable adjustment of reaction conditions was required to effect ketalization using tracer quantities of the ketone. In tissue distribution studies in estrogen-primed immature female rats, both ketals showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Additionally, metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. Both compounds showed relatively high uptake in fat, in accord with their relative lipophilicities demonstrated by HPLC-derived octanol-water partition coefficients. The selective uterine uptake and metabolic stability of these compounds suggests that this class of PgR ligands might be promising for the selective imaging of receptor positive tumors if derivatives of reduced lipophilicity can be prepared. PMID- 8487254 TI - Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies. AB - To gain insight into the specificity of cytochrome P-450 2D6 toward inhibitors, a preliminary pharmacophore model was built up using strong competitive inhibitors. Ajmalicine (1), the strongest inhibitor known (Ki = 3 nM) was selected as template because of its rigid structure. The preliminary pharmacophore model was validated by performing inhibition studies with derivatives of ajmalicine (1) and quinidine (9). Bufuralol (18) was chosen as substrate and the metabolite 1' hydroxybufuralol (19) was separated by high performance liquid chromatography. All incubations were carried out using human liver microsomes after demonstration that the Ki values obtained with microsomes were in accordance with those obtained with a reconstituted monooxygenase system containing purified cytochrome P-450 2D6. Large differences of Ki values ranging between 0.005 and 100 microM were observed. Low-energy conformers of tested compounds were fit within the preliminary pharmacophore model. The analysis of steric and electronic properties of these compounds led to the definition of a final pharmacophore model. Characteristic properties are a positive charge on a nitrogen atom and a flat hydrophobic region, the plane of which is almost perpendicular to the N-H axis and maximally extends up to a distance of 7.5 A from the nitrogen atom. Compounds with high inhibitory potency had additional functional groups with negative molecular electrostatic potential and hydrogen bond acceptor properties on the opposite side at respective distances of 4.8-5.5 A and 6.6-7.5 A from the nitrogen atom. The superposition of strong and weak inhibitors led to the definition of an excluded volume map. Compounds that required additional space were not inhibitors. This is apparently the first pharmacophore model for inhibitors of a cytochrome P-450 enzyme and offers the opportunity to classify compounds according to their potency of inhibition. Adverse drug interactions which occur when both substrates and inhibitors of cytochrome P-450 2D6 are applied may be predicted. PMID- 8487255 TI - 5-[4-(benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives and related analogues: new reversible, highly potent, and selective monamine oxidase type B inhibitors. AB - Thirty-three new 5-[4-(benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives including related analogues, designed as inhibitors of monoamine oxidase type B (MAO B), were synthesized and investigated both in vitro and ex vivo for their abilities to inhibit selectively rat brain MAO B over MAO A. Three inhibitors were found to act as reversible, highly potent, and selective MAO B inhibitors, namely the nitrile derivative 5-[4-(benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4 oxadiazol-2(3H)-one (12a) and two closely related homologues, the corresponding oxadiazolethione 13a and the alcohol 14b. Their IC50 (MAO B) values are in the low nanomolar range of 1.4-4.6 nM and their selectivities, estimated by the ratio of IC50 values (A/B), are from 3200 to > 71,400. Compound 12a exhibited the highest activity against MAO B. Its IC50 was evaluated to be 1.4 nM with a quasitotal selectivity (> 71,400) toward this enzyme. In ex vivo studies, 12a showed a reversible and short duration of action. MAO B was markedly inhibited with the oral dose of 1 mg/kg without any alteration of MAO A, and the inhibition almost did not exceed 24 h. Its ED50 (1 h after oral administration) was evaluated to be 0.56 mg (1.7 mumol)/kg. Remarkably, MAO A was not affected at doses as high as 1500 mg/kg, po. In addition, no apparent toxicity or behavioral anomaly was observed during the treatment even at the maximum administrated dose. SAR studies emphasize the existence of three binding sites to the enzyme with a special importance of the terminal phenyl. Analysis of the inhibition kinetics indicated that 12a acts in a two-step mechanism as a competitive, slow, and tight binding inhibitor of MAO B with a Ki value of 0.22 microM and an overall Ki* value at equilibrium of 0.7 nM. PMID- 8487256 TI - Synthesis and structure-activity relationships of novel benzimidazole and imidazo[4,5-b]pyridine acid derivatives as thromboxane A2 receptor antagonists. AB - A series of 1-benzylbenzimidazole and 3-benzylimidazo[4,5-b]pyridine substituted in the 2-position by an alkanoic or mercaptoalkanoic acid chain was synthesized for evaluation as potential thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor antagonists. The affinity of each compound for washed human platelet TXA2/PGH2 receptors was determined by radioligand binding studies using [125I]PTA-OH. Structure-activity relationships led to the conclusions that 2-alkanoic acid derivatives were slightly more potent than 2-mercaptoalkanoic acids and that compounds possessing a 3,3-dimethylbutanoic acid in the 2-position were definitely the most potent with Ki values of 4-39 nM (11a, 11g-x, 37a, 37f-o, 23a c). The replacement of this 3,3-dimethylbutanoic acid side chain by a shorter one led to a marked decrease of affinity (11b and 11c; Ki = 5600 and 1700 nM, respectively). Compounds of benzimidazole and imidazo[4,5-b]pyridine series displayed similar potencies (11q and 23c have Ki values of 6 and 7 nM, respectively). The interesting pharmacological profile of compound 23a (UP 116 77: 4-[3-[(4-chlorophenyl)methyl]-6-chloroimidazo[4,5-b]pyridin-2-yl]- 3,3 dimethylbutanoic acid) and its excellent tolerance led us to select this derivative for further development. PMID- 8487257 TI - New indole derivatives as potent and selective serotonin uptake inhibitors. AB - A series of new indole derivatives (2-28) has been prepared in the search for novel 5-HT uptake inhibitors. These compounds were obtained by the condensation of N-(chloroalkyl) naphthalenesultam derivatives with the appropriate amine in presence of a base, at reflux of DMF or THF. The yields were moderate (12-56%), except for the piperazine derivative 20 (85%). The affinity of the compounds for uptake site and 5-HT2, alpha 1, and D2 receptors was measured. Some compounds were studied in vivo by their potentiating effect of 5-HTP-induced symptomatology. The most potent and selective (uptake, 5-HT2 versus alpha 1, D2 sites) compounds contain a 3-[(4-piperidinyl)methyl]indole moiety. 5-Fluoro-3-[(4 piperidinyl)methyl]indole itself (compound 1) displayed a high affinity for the uptake site but was devoided of in vivo activity. N-Methylation of this compound abolished the affinity. In contrast N-substitution by a two-carbon chain linked to a naphthalenesultam or related heterocycle led to compounds exhibiting high affinity for the uptake site. One of them, 1-[2-[4-((5-fluoro-1H-indol-3 yl)methyl-1- piperidinyl]ethyl]-5,6-dihydro-1H,4H-1,2,5-thiadiazolo[4,3,2- ij]quinoline 2,2-dioxide (compound 24), was found as active as fluoxetine in vivo. PMID- 8487258 TI - Structure-function studies of amphiphilic antibacterial peptides. AB - The synthesis of 11 peptides, ranging in composition from 9 to 17 amino acid residues, by solid-phase methodology was accomplished with the purpose of studying how the amphiphilic and hydrophobic character, the size of the molecule, and the charge distribution modulate the antibacterial activity. It was found that peptides composed of 16 and 17 amino acid residues, with high hydrophobic (mainly due to Trp or Phe) and hydrophilic (due to Lys) character distributed along opposite amphiphilic faces, showed considerable antibacterial activity against clinically isolated bacteria together with Gram positive and Gram negative ATCC bacterial strains. However, the hemolytic capacity of the peptides was also significant. Decreasing the hydrophobic character of the molecule by replacing Trp or Phe with Leu residues while maintaining the basic contribution of Lys drastically reduced the hemolytic activity and only slightly decreased the bioactivity. Peptides composed of 9-10 amino acid residues with high hydrophobic and basic nature possess antibacterial activity but, in general, are less active than the larger counterpart peptides. By replacing all Trp residues of a short peptide by Leu residues, the activity was considerably reduced. Circular dichroism studies and antibacterial assays showed that shorter peptides with very low helical content, and thus deprived of amphiphilic character, still have appreciable bioactivity. This observation, coupled with the fact that due to their small size they cannot span the bacterial outer lipid bilayer, may suggest different mechanisms of action for long-chain vis-a-vis short-chain peptides. PMID- 8487259 TI - Molecular shape comparison of angiotensin II receptor antagonists. AB - A new and powerful analytical method for comparing molecular shapes by optimizing the overlap of molecular volumes has been developed. This shape comparison method provides both a quantitative measure of the shape similarity of molecules and a means to align molecules such that shape similarity if maximized. Our MSC method has been enhanced with an option to allow discrimination between groups with different chemical properties. Atoms or groups of atoms may be assigned to different classes based on specific properties such as electrostatic potential, hydrogen bonding ability, or hydrophobicity. This enables matches based on criteria such as alignment of hydrophobic groups or hydrogen bond acceptor groups. In this study, we report shape comparisons of angiotensin II (AII) receptor antagonists from two structural classes, 4-(biphenyl-4-ylmethoxy) quinoline derivatives such as ICI D8731 and N-(biphenyl-4-ylmethyl)imidazole derivatives, such as DuP753. Starting with a list of low-energy conformations for the two molecules, each conformation of the first molecule is paired with each of the conformations of the second molecule. For each of these conformational pairs, an MSC comparison, which generates multiple MSC maxima, is initiated. Eight high scoring conformational pairings were found with shape matching based on the intersection of the total molecular volume, while nine high-scoring pairs were identified with matching by atom type. MSC identifies conformational pairs with high shape similarity, as measured by the intersection volume, and thus generates and prioritizes several alternative models for the AII antagonist pharmacophore. PMID- 8487260 TI - Hybrids of antibiotics inhibiting protein synthesis. Synthesis and biological activity. AB - Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of procaryotic and eucaryotic protein synthesis as well as potential antimicrobial agents. Lincophenicol (1c) was active as inhibitor of Escherichia coli ribosomal peptidyltransferase-catalyzed puromycin reaction. Both lincophenicol (1c) and sparsophenicol (1b) inhibited the binding of the iodophenol analogue of sparsomycin to E. coli ribosomes. The results are discussed in terms of a retro inverso hypothesis advanced earlier for interpretation of biological activity of chloramphenicol (1a) and sparsophenicol (1b). Chloramlincomycin (5a) suppressed the growth of Streptococcus pyogenes with MIC 6.25 micrograms/mL. PMID- 8487261 TI - New nonpeptide angiotensin II receptor antagonists. 3. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4 (biphenylylmethoxy)pyridine derivatives. AB - A novel series of nonpeptide angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 3-substituted 2,6-dialkylpyridine. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.005-0.5 microM. A variety of substituents was found to be effective at the 3-position of the pyridine ring. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-1.0 mg/kg. One of the compounds, 2-ethyl-5,6,7,8-tetrahydro-4-([2'-(1H-tetrazol-5 yl)biphenyl-4y l] methoxy)quinoline (26), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg po in AII-infused, conscious, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model compound 26 showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg po. Based on its profile, this compound, designated ICI D6888, has been selected for evaluation in volunteers. PMID- 8487262 TI - Site-specific conjugation of a radioiodinated phenethylamine derivative to a monoclonal antibody results in increased radioactivity localization in tumor. AB - The preparation of a novel radioiodination reagent, the (aminooxy)acetyl derivative of (p-[125]-iodophenyl)ethylamine, is described. Conventional radioiodination of proteins involves the formation of iodotyrosine residues, but for in vivo applications such as thyroid or stomach immunoscintigraphy, the susceptibility of these residues to tissue dehalogenases constitutes a serious disadvantage. Using our new compound, which has a particularly nonreactive aromatic ring, we confirm and extend studies published by other workers indicating the much greater in vivo stability of iodophenyl compounds compared to the more conventional iodophenolic ones. In addition, the aminooxy group of our reagent gives a stable and specific linkage to aldehyde groups formed by periodate oxidation on the sugar moiety of antibody molecules. In vitro, favorable binding activity and high stability was obtained with a (([125I]iodoaryl)amino)oxy labeled monoclonal antibody directed against carcinoembryonic antigen. In vivo, using paired labeling experiments in nude mice bearing colon carcinoma xenografts, the (([125I]iodoaryl)amino)oxy-MAb (MAb = monoclonal antibody) was compared with the same MAb 131I-labeled by conventional chloramine-T method. Tumor 125I concentration of (arylamino)oxy MAb (measured as percent injected dose per gram) was significantly higher as compared to values obtained with a conventionally labeled 131I antibody. Additionally, thyroid uptake, an indicator of iodine release from the antibody, was up to 25 times lower after injection of 125I-MAb obtained by the new method as compared to the conventionally iodinated 131I-MAb. PMID- 8487263 TI - Benzylamine antioxidants: relationship between structure, peroxyl radical scavenging, lipid peroxidation inhibition, and cytoprotection. AB - Three homologous series of 3,5-dialkoxy-4-hydroxybenzylamines were prepared and tested (1) as peroxyl radical scavengers in homogeneous aqueous solution, (2) as inhibitors of iron-dependent peroxidation of rabbit brain vesicular membrane lipids, and (3) as cytoprotective agents using primary cultures of rat hippocampal neurons exposed to hydrogen peroxide. The structural requirements for efficient radical trapping in homogeneous solution differed from those for effective lipid peroxidation inhibition: In homogeneous solution a kinetic preference existed for smaller, less sterically encumbered substituents flanking the reactive phenolic hydroxyl group. Lipid peroxidation inhibition, on the other hand, required longer more lipophilic substituents. Consequently, a lipophilic alkoxyl substituent at C3 and a small substituent at C5 appeared optimal for efficient radical scavenging activity in both lipid and homogeneous solution. Maximal cytoprotection of rat hippocampal neurons exposed to hydrogen peroxide was also associated with more lipophilic derivatives although substituent length and substituent bulk may represent independent parameters for relating structure and efficacy in this system. PMID- 8487264 TI - Thyroid hormone uptake by hepatocytes: structure-activity relationships of phenylanthranilic acids with inhibitory activity. AB - The synthesis of a series of mono- and disubstituted N-phenylanthranilic acids is described. Substituents on the phenyl ring include Cl, CN, OH, CF3, Br, I, CH3, OCH3, and OCF2CF2H. These compounds have been tested for their inhibitory effect on triiodothyronine (T3) uptake by H4 hepatocytes. The nonsteroidal antiinflammatory drugs flufenamic acid, mefenamic acid, and meclofenamic acid and the structurally related compounds 2,3-dimethyldiphenylamine and diclofenac were also tested. The most potent compounds were found to be, in order of decreasing activity, meclofenamic acid (2,6-Cl2,3-CH3), flufenamic acid (3-CF3), mefenamic acid (2,3-(CH3)2), and the compounds with 3,5-Cl2 and 3-OCF2CF2H substituents. The least potent compounds had 3-CN and 3-OH substituents. An analysis of quantitative structure-activity relationships (QSAR) for the series of phenylanthranilic acids showed that the inhibition of T3 uptake is highly dependent on the hydrophobicity of the compound. The relationship between uptake inhibition and the calculated octanol-water partition coefficient (clogP) was found to be parabolic, with optimum inhibitory activity found when the clogP of the phenylanthranilic acid was 5.7. It was also found that the 1-carboxylic acid group of the phenylanthranilic acids was not a prerequisite for uptake inhibition to occur, but its removal or alteration resulted in reduced inhibition. PMID- 8487265 TI - Molecular size and flexibility as determinants of selectivity in the oxidation of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs by monoamine oxidase A and B. AB - The introduction of a methylene bridge between the phenyl and tetrahydropyridyl moieties of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in increased selectivity for monoamine oxidase B (MAO B) over monoamine oxidase A (MAO A). However, lengthening of this bridge results in a total loss of selectivity. In the present study, a number of isomeric 4-naphthyl-, 4 (naphthylalkyl)-, 4-thienyl-, and 4-(thienylalkyl)tetrahydropyridines, conformationally restrained and flexible analogs of MPTP, were synthesized and evaluated as potential selective substrates of MAO A and B. In terms of the parameter (turnover number)/Km, the bulky naphthyl analogs were invariably better substrates of MAO A than kynuramine, the reference substrate for this enzyme. In addition, all naphthyl analogs, regardless of conformational mobility, were more effective substrates of MAO A than MAO B. Similarly, all thienyl analogs were found to be more effective substrates of MAO B. In contrast to the naphthalenes, the conformationally restrained thiophenes 9a and 10a were found to be poor substrates of MAO B, relative to benzylamine, the reference substrate. These results suggest that the selectivity of these compounds for either MAO A or B is determined by the complex interplay of molecular size and flexibility. In this interplay, either one of these two factors may predominate. PMID- 8487266 TI - Design and synthesis of 18F-labeled neurotoxic analogs of MPTP. AB - We report on the synthesis of two fluorine-18 labeled analogs of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP). A piperidyl triazene was fluorinated to produce [18F]-1-methyl-4-(2-fluorophenyl)-1,2,3,6-tetrahydropyridine (2'-F-MPTP, 12) in very low yield, and 1-methyl-4-[2-(fluoromethyl)phenyl]-1,2,3,6 tetrahydropyridine (2'-FCH2-MPTP, 11) was labeled with 18F by nucleophilic displacement of the corresponding chloride in 60% yield. The biodistribution in mice of the latter radiotracer and its oxidation to 1-methyl-4-[2 (fluoromethyl)phenyl]pyridinium (2'-FCH2-MPP+, 6) is also reported. The kinetics of oxidation of 2'-FCH2-MPTP and its solvolysis products (the corresponding 2' hydroxymethyl and 2'-chloromethyl analogs) by rat liver monoamine oxidase were investigated. 2'-FCH2-MPTP accumulated to a useful degree in the brain, was oxidized by monoamine oxidase in vitro, was converted to the oxidation product in brain in vivo, and had a neurotoxic potency similar to that of MPTP. We feel it may be useful as an 18F-labeled radiopharmaceutical for positron tomographic studies of the mechanisms of MPTP toxicity. PMID- 8487267 TI - Statistics using neural networks: chance effects. PMID- 8487268 TI - Prenatal diagnosis of diastrophic dysplasia with polymorphic DNA markers. AB - Ultrasonography is a non-invasive method for prenatal detection of diastrophic dysplasia (DTD) in the second trimester of pregnancy. As there is a need for genetic counselling as early as possible we wished to develop a method based on molecular analysis. Five fetuses in families with a previous history of DTD were studied by typing them and their relevant family members for DNA markers closely linked to the DTD gene. The DNA analyses predicted that three of the fetuses were unaffected and two affected. These results were concordant with those obtained by ultrasonography, and the phenotype of the fetus was correctly predicted in all cases. DNA analysis provides a reliable means of prenatal diagnosis in the first trimester of pregnancy. PMID- 8487269 TI - Possible X linked congenital mitochondrial cardiomyopathy in three families. AB - Familial cases of childhood congestive cardiomyopathy with X linked recessive inheritance and abnormalities of heart muscle mitochondria have been previously reported. We report here three families with possible X linked congestive cardiomyopathy and specific mitochondrial abnormalities. The heart disorder presented as endocardial fibroelastosis with neonatal death in two brothers in one family, and as heart failure and death in infancy in two brothers in the other two families. In one family a maternal uncle may also have been affected. Pyodermia and neutropenia was reported in one of the boys. Electron microscopy of heart muscle after necropsy showed increased numbers of mitochondria and abnormal mitochondrial crystal condensations and paracrystalline inclusions in all sibships. Barth's syndrome has been mapped to Xq28 and includes cardiomyopathy, skeletal muscle myopathy, neutropenia, and mitochondrial abnormalities similar to those found in the three families reported here. Since the clinical picture differed in the three families, they may represent more than one entity. PMID- 8487270 TI - Gaucher's disease in the United Kingdom: screening non-Jewish patients for the two common mutations. AB - Twenty-six patients with Gaucher's disease diagnosed in the United Kingdom and two obligate carriers, all of non-Jewish origin, were screened for the two common disease causing mutations and two rarer mutations in the glucocerebrosidase gene. These mutations are referred to as N370S, L444P, Ins84G, and 1066 + 1G-->A, respectively. The results showed that out of 54 alleles screened, 26% were N370S, 35% were L444P, and the remaining 39% were rare or undefined. The results also showed a clear correlation between the presence of at least one N370S allele and mild disease. PMID- 8487271 TI - Phenylketonuria: variable phenotypic outcomes of the R261Q mutation and maternal PKU in the offspring of a healthy homozygote. AB - Phenylketonuria (PKU) and benign hyperphenylalaninaemia (HPA) result from a variety of mutations in the gene for the hepatic enzyme phenylalanine hydroxylase. PKU has been found in the Israeli population in two variants, classical and atypical. The two are clinically indistinguishable and require treatment with low phenylalanine diet to prevent mental retardation, but show differences in serum phenylalanine levels and in tolerance to this amino acid. Maternal PKU is a syndrome of congenital anomalies and mental retardation that appears in offspring of PKU mothers as a result of fetal exposure to the high phenylalanine level in the maternal blood. We studied a family in which two children with severe, classical PKU and their unaffected brother showed mild signs of maternal PKU. Their mother had no clinical signs of PKU, but the phenylalanine concentration in her serum reached a level that usually characterises PKU patients. This woman represents a rare phenotype, benign atypical PKU. Such 'hidden' PKU in women may lead to maternal PKU in the offspring, similar to overt PKU. Special attention should therefore be paid to women having children with any of the clinical hallmarks of maternal PKU, and to children born to women known to have benign HPA. The mother was also found to be homozygous for a missense mutation at the phenylalanine hydroxylase locus, R261Q, which does not abolish enzymatic activity completely. In two other families, homozygosity for this mutation resulted in atypical PKU in four children. This observation suggests that mutations that do not completely destroy phenylalanine hydroxylase activity may exhibit variable phenotypic expression which is unpredictable. Compound heterozygosity for R261Q and other mutations led in other patients either to classical PKU or to mild benign HPA. PMID- 8487272 TI - Onset symptoms in 510 patients with Huntington's disease. AB - The onset of Huntington's disease (HD) is preceded or accompanied by events and symptoms which contribute to the natural history of the disease. Data obtained from the first 510 completed 'Questionnaires for Affected Individuals', recorded by the National Huntington's Disease Research Roster (NHDRR) were analysed. The following features were evaluated: (1) neurological and psychiatric onset symptoms; (2) the precipitating effect of stressful events and drugs; (3) the modification after onset of smoking and alcohol consumption. The most frequent psychiatric onset symptom was depression. Stressful events in the year before onset occurred in 43% of patients. However, onset age was the same in patients with and without previous stressful events. Smoking and especially alcohol consumption showed a decreasing trend after onset. PMID- 8487273 TI - Suicide risk in Huntington's disease. AB - In order to evaluate the relevance of suicide risk in families affected by Huntington's disease (HD), 2793 subjects registered with the National Huntington's Disease Research Roster were studied. Suicide was the reported cause of death in 205 subjects (7.3%). This group included affected and possibly affected subjects, subjects at 50% and 25% risk, possibly at risk subjects, and normal relatives. In all categories suicide was more frequent than in the general US population. The data suggest that suicide is quite frequent in some families with HD. This increased suicide risk must be carefully considered in planning genetic counselling for predictive testing in HD. PMID- 8487274 TI - Polydactyly: a study of a five generation Indian family. AB - Preaxial polydactyly was observed in up to five generations of an Indian family living in a village in the Rajkot district (Gujarat). Among the 71 affected members, 45 were males and 26 were females. All these affected members showed preaxial polydactyly manifesting as a well formed, articulated extra digit of the hand or foot. Twenty other cases were also identified with polydactyly involving triphalangeal digits replacing the thumbs or duplication of the big toe(s). To the best of our knowledge, the present family is the largest in which several members have preaxial polydactyly of different types. No other abnormalities were apparent. The present study strongly suggests that preaxial polydactyly with a well formed extra digit, triphalangeal thumbs, and duplication of the big toe can be manifestations of the same autosomal dominant gene. It is likely that other factors are modifying the expression of this gene. PMID- 8487275 TI - Characterisation of a highly polymorphic microsatellite at the DXS207 locus: confirmation of very close linkage to the retinoschisis disease gene. AB - Juvenile retinoschisis (RS) is an X linked recessive vitreoretinal disorder for which the basic molecular defect is unknown. The gene for RS has been previously localised by linkage analysis to Xp22.1-p22.2 and the locus order Xpter-DXS16 (DXS43, DXS207)-RS-DXS274-DXS41-Xcen established. To improve the resolution of the genetic map in the RS region, we have isolated a highly polymorphic microsatellite at DXS207, which displays at least nine alleles with a heterozygosity of 0.83. Using this microsatellite and four other Xp22.1-p22.2 marker loci, DXS16, DXS43, DXS274, and DXS41, we performed pairwise and multilocus linkage analysis in 14 kindreds with RS. The microsatellite was also typed in the CEPH (Centre d'Etude du Polymorphisme Humain) reference families. Tight linkage was found between RS and DXS207 (Z(theta) = 14.32 at theta = 0.0), RS and DXS43 (Z(theta) = 8.10 at theta = 0.0), and DXS207 and DXS43 (Z(theta) = 40.31 at theta = 0.0). Our linkage results combined with data previously reported suggest that the DXS207-DXS43 cluster is located less than 2 cM telomeric to the RS locus. The microsatellite reported here will be a very useful marker for further linkage studies with retinoschisis as well as with other diseases in this region of the X chromosome. PMID- 8487276 TI - An improved, non-isotopic method of screening cells from patients with abnormalities of sexual differentiation for Y chromosomal DNA content. AB - The detection of 45,X/46,XY mosaicism in patients with abnormalities of sexual differentiation is of crucial diagnostic importance. Here we present application of a PCR based method of detection of alphoid repeats of Y chromosomal origin. The method detects 0.01% of male DNA on a female DNA background. Out of 28 patients studied, in all cases where the Y chromosome or a part of it containing centromeric sequences was present, a positive amplification signal of Y chromosomal alphoid repeats was detected. In five cases the Y origin of marker chromosomes was diagnosed. The pattern of amplification signal distribution of the SRY gene was identical to that of Y specific alphoid primers, which confirms applicability of this method in the molecular diagnostic laboratory. The other diagnostic advantage is the ability to use dried blood specimens as an easy to handle and efficient source of DNA. PMID- 8487277 TI - Otopalatodigital syndrome type II. PMID- 8487278 TI - A cytogenetic survey in Menkes disease: implications for the detection of chromosomal rearrangements in X linked disorders. PMID- 8487279 TI - Prevalence of cystic fibrosis mutations in the Grampian region of Scotland. AB - We have identified all known sufferers of cystic fibrosis (CF) alive in the Grampian region, north east Scotland, on 1 January 1989. DNA samples were obtained for a prevalence study of the common mutations with near to complete ascertainment. A relatively high prevalence of the delta F508 mutation was found (82%), with one of four mutations being present on 92% of CF chromosomes. The high prevalence of these four easily detectable mutations in Grampian has local implications for genetic counselling, the efficacy of population carrier screening, and the usefulness of mutation analysis in cases where the diagnosis of CF is in doubt. PMID- 8487280 TI - Absence of linkage between chromosome 21 loci and familial amyotrophic lateral sclerosis. AB - Familial amyotrophic lateral sclerosis (FALS) has recently been shown to be linked to chromosome 21 markers in a subset of families. However, we were unable to show linkage between FALS and chromosome 21 markers which flank the putative FALS locus in UK families. PMID- 8487281 TI - Profound mental retardation, characteristic facies with midfacial hypoplasia and premature frontotemporal balding, muscular hypotrophy, and small patellae in two unrelated male patients. AB - Two profoundly mentally retarded, unrelated males are reported with an unidentified multiple congenital anomaly/mental retardation syndrome, including early balding, patella luxations, small hands and feet, and hypogonadism, similar to a previous publication in this journal of a severely mentally retarded male patient with dysmorphic features. PMID- 8487282 TI - Short limbed dwarfism, genital hypoplasia, sparse hair, and vertebral anomalies: a variant of Ellis-van Creveld syndrome? AB - A male newborn with acromesomelic short limbed dwarfism, genital hypoplasia, and vertebral anomalies is reported. As the child had an important number of clinical and radiological symptoms seen in patients with Ellis-van Creveld syndrome, we raise the question of whether he may represent a variant example of this syndrome despite the absence of cardinal symptoms such as postaxial polydactyly and ectodermal changes (nail hypoplasia). PMID- 8487283 TI - Consanguinity, cardiac arrest, hearing impairment, and ECG abnormalities: counselling pitfalls in the Romano-Ward syndrome. AB - Genetic counselling in the autosomal dominant condition of the Romano-Ward syndrome might be assumed to be relatively straightforward. The problems posed by consanguinity, deafness, and subclinical gene carriers in a pedigree with this condition have caused us to reevaluate this view. The diagnostic and management difficulties which may attend this potentially fatal condition are highlighted by our experience with this family. PMID- 8487284 TI - Coarctation of the aorta, interrupted aortic arch, and hypoplastic left heart syndrome in three generations. AB - Five members in three generations of a family were affected by a congenital heart disease. Four of them had mild or severe coarctation of the aorta (CoA), either isolated or in association with other cardiac defects. Fetal echocardiography allowed prenatal diagnosis in one pregnancy at risk. This family suggests that a rare form of CoA could be the result of an autosomal dominant mutation with high penetrance and variable expressivity rather than polygenic inheritance. PMID- 8487285 TI - Simultaneous de novo interstitial deletion of 16q21 and intercalary duplication of 19q in a retarded infant with minor dysmorphic features. AB - We report on a retarded infant with minor dysmorphic features in whom deletion 16 and duplication 19q were discovered. The karyotype is 46,XX,del(16) (q13.08 21.05),dup(19)(q13.13-13.2). The origin and significance of the aberrant chromosomes are unknown. PMID- 8487286 TI - MRSA: major problem or minor threat? PMID- 8487287 TI - A review of the correlation of T-agglutination patterns and M-protein typing and opacity factor production in the identification of group A streptococci. AB - The classical techniques of M protein and opacity factor (OF) typing and T agglutination typing remain the "gold standard" in identifying group A streptococci, although newer techniques have been proposed to assist laboratory scientists, microbiologists, epidemiologists and clinicians in the precise identification and characterisation of these organisms. Because of the current scarcity of M-typing sera and the increased use by many laboratories of T typing as the sole method of group A identification, a table is presented to indicate specific correlation between the T-agglutination pattern and the M serotype. The use of this table will enable not only more selective use of typing sera but also, perhaps, result in improved understanding and ultimately in correlating these defined patterns with newer and more sensitive techniques. PMID- 8487288 TI - Pathological changes in the rabbit ileal loop model caused by Campylobacter jejuni from human colitis. AB - Four strains of Campylobacter jejuni isolated from children with inflammatory diarrhoea were assayed in the rabbit ileal loop model of infectious diarrhoea. All caused inflammatory reactions with severe macroscopic and microscopic damage in infected rabbit ileal tissue similar to that observed in the patients by endoscopy and histological analysis of colonic biopsies. Haemoglobin and other proteins were observed in loop fluids, consistent with leakage of serum from damaged mucosa. Loop fluids also contained significant bicarbonate concentrations, indicative of an active secretory component similar to that in control loops inoculated with cholera toxin. However, although three of the four clinical strains produced small amounts of a protein immunologically related to cholera toxin in vitro, none such was detected in either tissues or fluids of infected ileal loops. We propose instead that host-derived mediators of secretion may be important in pathogenesis. A mutant strain of C. jejuni with impaired motility, obtained from the National Collection of Type Cultures, did not induce tissue damage or fluid secretion in rabbit ileal loops. PMID- 8487289 TI - Typing of Listeria spp. by random amplified polymorphic DNA (RAPD) analysis. AB - Random amplified polymorphic DNA (RAPD) analysis, a variation of the polymerase chain reaction (PCR) in which a single primer is used, was evaluated for use as a simple and reliable method with which to type Listeria spp. Representatives of six species of Listeria were studied. Five isolates of L. innocua and four isolates of L. seeligeri were all distinguishable from one another, but the four isolates of L. ivanovii tested, although distinguishable from other Listeria spp., were not differentiated. Among L. monocytogenes serovars 1/2a (eight isolates), 1/2b (eight isolates) and 4b (10 isolates), at least six, three and six RAPD patterns were observed, respectively. Fourteen neonatal cross-infection sets of L. monocytogenes isolates, shown to be indistinguishable by serotyping and phage typing, were examined with three different primers. With one primer, three of the sets were shown to consist of closely related, but distinguishable, strains. In the other 11 cases, each set of strains was indistinguishable with all three primers. These preliminary data indicate that RAPD analysis has promise as a method for typing Listeria spp. PMID- 8487290 TI - Effect of clearance of bacteria from the blood on the development of systemic bacteraemia in mice. AB - Clearance of various bacteria isolated from portal and systemic blood of mice was evaluated and compared. All portal blood strains, including Escherichia coli and enterococci were eliminated more rapidly from the circulation than were strains isolated from systemic blood, including Pseudomonas aeruginosa. With mannose-type lectin, mannose or fucose residues that mediated lectinophagocytosis were detected on the surfaces of most portal strains by agglutination tests. Blood clearance of Esch. coli H21 was inhibited by prior injection of mannose into mice, suggesting that the clearance of this strain was mediated by mannose-type lectin on the surface of tissue macrophages. However, no inhibition of clearance of any other strains was observed by the injection of mannose, galactose, or fucose into mice, nor by pre-incubation of bacteria with mannose. Blood clearance of some portal strains was significantly faster in CBA/J mice than in CBA/N mice with B cell immune deficiency, indicating that immunoglobulin was involved in their clearance. Among portal strains only enterococci showed high cell-surface hydrophobicity. These data suggest that initial bacteria blood clearance may be critical in determining whether latent portal bacteraemia progresses to systemic bacteraemia and that the rapid clearance of most strains is multifactorial. PMID- 8487291 TI - Oral infectivity and bacterial interactions with mononuclear phagocytes. AB - The purpose of this study was to clarify the association between the oral infectivity of a bacterial strain and its susceptibility to ingestion by mononuclear phagocytes or ability to survive within them. Ten bacterial strains tested--all of known oral infectivity--comprised Salmonella typhimurium, Listeria monocytogenes (three strains), Escherichia coli (two strains), Proteus mirabilis, Enterococcus faecalis, Bacteroides fragilis, and a Bacteroides sp. The phagocytic uptake of each strain was measured as the bacteria to phagocyte ratio after mononuclear phagocytes in mouse peritoneal exudate were permitted to ingest bacteria in vivo for 3 min. The three Listeria strains were the most susceptible to phagocytic uptake and the Salmonella strain was relatively resistant. The intracellular survival of each strain was studied during a subsequent 2 h in vitro incubation of the mononuclear phagocytes that had been permitted to ingest bacteria in vivo. The strains with the best intracellular survival were Ent. faecalis and two of the three Listeria strains. The ability of S. typhimurium to survive intracellularly was intermediate but better than that of the two E. coli strains. Oral infectivity was not consistently correlated with susceptibility to ingestion by mononuclear phagocytes or ability to survive within them. PMID- 8487292 TI - Clearance and tissue distribution of staphylococcal enterotoxin A in the rat and potential use of adsorbents for removal from plasma. AB - Many of the profound effects of staphylococcal septicaemia are thought to be the result of entry of enterotoxins into the systemic circulation. The aim of this study was to investigate the disposition of staphylococcal enterotoxin A (SEA) in the rat and its possible removal from blood. SEA labelled with 125I was administered intravenously (250 micrograms/kg) to rats. The blood clearance of SEA showed a biphasic pattern; an initial fast disappearance (half-life c. 3 min) was followed by a slower one (half-life c. 2 h). Thirty minutes after injection of 125I-labelled SEA, most of the radioactivity was concentrated in the kidneys, indicating that renal excretion was the main route of elimination of SEA. The adsorption capacities of polymer-coated activated charcoal (DHP-1 and Adsorba 150C), uncharged resin (Amberlite XAD-7), anion exchange resin (Dowex-1) and polymyxin B matrix were assessed by measurement of the equilibrium adsorption isotherms for SEA. DHP-1 charcoal, Amberlite XAD-7 resin and Dowex-1 resin adsorbed similar amounts of SEA in human plasma. Plasma perfusion experiments were performed in vitro with small columns containing either charcoal or resin adsorbents. Over 4 h perfusion, DHP-1 charcoal removed 50% of the initial amount of 125I-SEA, Adsorba 150C charcoal 8.1% of SEA and Amberlite XAD-7 resin 32.5% of SEA. These results suggest that it may be feasible to develop the adsorbent columns for direct removal of SEA from the plasma of patients with staphylococcal septicaemia. PMID- 8487293 TI - Comparison of two gene amplification methods for the detection of Toxoplasma gondii in experimentally infected sheep. AB - Efferent lymph and peripheral blood collected from sheep experimentally infected with Toxoplasma gondii strain S48 were analysed for parasite DNA by amplification of the B1 and P30 T. gondii genes by the polymerase chain reaction (PCR). The relative sensitivity of these two gene amplification methods was assessed and compared with parasite detection by mouse injection (MI). B1 PCR was consistently more sensitive than P30 PCR and the results agreed closely with those from MI. By contrast, P30 PCR gave more than twice as many false negatives results than B1 PCR. The few apparent false positive results given by either PCR method were probably due to the inability of MI to detect non-viable parasites. All specimens collected before infection with T. gondii gave negative results by PCR and MI. Parasite DNA was detected by both B1 and P30 PCR in the lymph node of a sheep 12 days after infection but not in other tissues. The results permit a direct comparison between T. gondii detection by P30 and B1 PCR. Moreover, they further confirm the value of PCR detection of toxoplasma as a sensitive, specific and reliable diagnostic and research tool. PMID- 8487294 TI - Ultrastructure and biochemical studies of the flagellar sheath of Helicobacter pylori. AB - Helicobacter pylori flagellar sheaths were isolated by sucrose density-gradient centrifugation and analysed by electronmicroscopy, SDS-PAGE and gas-liquid chromatography. Electronmicroscopy of thin sections of flagella showed an internal electron-dense filament and a surrounding flagellar sheath with the typical bilayer structure of a membrane. The flagellar filaments could be disintegrated by acid treatment and the resulting isolated flagellar sheaths formed vesicles, sometimes with characteristic structures. Centrifugation of flagellar preparations after acid treatment resulted in the enrichment of flagellar sheaths in the pellet. SDS-PAGE analysis of the pellet showed a reduction of the flagellin band and a number of protein bands of 150, 76, 67, 65, 53, 51, 49, 29.5, 18, 17 and 16 kDa. However, there were no major protein bands characteristic for the sheath. Differences between the protein profiles of Sarkosyl-insoluble membranes and flagellar sheaths appeared in the lower M(r) range of 30-14 kDa. Major fatty acids of isolated flagellar sheaths were C 14:0, C 19:0 cyc, C 18:0, and the LPS-specific fatty acids 3-OH C 16:0 and 3-OH C 18:0. The results demonstrate that the flagellar sheaths of H. pylori are membranes and contain LPS and proteins. PMID- 8487295 TI - Outer-membrane protein and immunoblot analysis of Australian isolates of Haemophilus influenzae. AB - Strains of Haemophilus influenzae isolated from children in South Australia and the Northern Territory with systemic infections (mostly meningitis or epiglottitis) were subjected to serotyping, biotyping, outer-membrane protein (OMP) analysis and immunoblot subtyping. All 65 isolates examined were from blood or cerebrospinal fluid; 59 (91%) of the strains were identified as type b and the remainder as either type a (two strains) or non-typable (four strains). Of the 59 type b strains, 45 (76%) belonged to a single OMP subtype (equivalent to subtype 3L in the Barenkamp scheme); the remaining type b strains belonged to five other OMP subtypes. No correlation was apparent between OMP subtype and geographical region, clinical diagnosis or antimicrobial drug susceptibility pattern. Immunoblot subtyping enabled nine (18%) of 41 strains belonging to the principal OMP subtype to be distinguished from the remainder. PMID- 8487296 TI - Detection of Clostridium difficile enterotoxin gene in clinical specimens by the polymerase chain reaction. AB - A rapid assay was developed for detection of the Clostridium difficile enterotoxin gene in stool specimens by means of the polymerase chain reaction (PCR). The PCR primers amplified a 63-bp repetitive sequence of the enterotoxin gene, thereby generating a distinctive ladder pattern of DNA bands following electrophoresis. Crude DNA extracts from stools containing C. difficile produced one (63-bp) or more bands of the characteristic ladder. Of 172 stool specimens from 58 patients, 37 gave positive results by culture (15 specimens) or cytotoxin assay (36 specimens). When 36 available "positive" specimens were tested by the PCR assay, 34 (94%) gave positive results--24 by direct testing, and 10 after extraction of DNA by the Qiagen procedure. Insufficient material of the remaining two specimens was available for DNA extraction. Of 21 stools "negative" for C. difficile by culture or cytotoxin assay, one gave a positive result by PCR and seven produced atypical bands. The rapid PCR detection technique for C. difficile was more sensitive than standard culture, and of a sensitivity similar to cytotoxin testing. The method has the potential for adoption in routine laboratory practice. PMID- 8487297 TI - Highly cooperative DNA binding by the coliphage HK022 repressor. AB - The CI repressor protein from the temperate lambdoid phage HK022 was purified to near homogeneity and used in DNase I footprinting analyses to identify six binding sites in this phage. All these sites contained homologous 15 bp inverted repeats. Three of these 15 bp inverted repeats were located between the cI and cro (OR1 to OR3), and the other three were 3' to the cI gene (OL1 to OL3). Two of these sites were identified as operator sites for the repressor by DNA sequence analyses of virulent phage mutants. Almost all these mutations identified lay within the 15 bp inverted repeats comprising OR1 and OR2, and almost all were in the most highly conserved positions in the operators. The majority of virulent mutants contained mutations in both OR1 and OR2. Intrinsic affinities for individual operators were measured by DNase I footprinting analyses using DNA fragments which contained a single wild-type operator adjacent to two mutant operators. Comparison of these values with the affinity observed with these sites in the wild-type operator indicated that HK022 CI repressor bound cooperativity to OR1 and OR2 with a cooperativity parameter, omega, of almost 2000. Cooperative binding occurred in an alternative pairwise fashion, as previously seen with lambda CI repressor. In addition to cooperative binding between two adjacent operators, the repressor also increased the affinity for adjacent non-specific DNA sites, resulting in a periodic pattern of binding termed "phasing". This phasing pattern extended beyond regions predicted for pair-wise interaction, but was significantly decreased on a template with two adjacent operators, suggesting that pairwise cooperativity interfered with phasing. PMID- 8487298 TI - Plant bZIP protein DNA binding specificity. AB - Plant bZIP proteins exhibit a relaxed DNA-binding specificity for DNA sequence motifs containing an ACGT core. Gel mobility shift experiments employing ten different recombinant plant bZIP proteins demonstrated that nucleotides flanking the ACGT core affected binding specificity and identified three different types of ACGT elements: G-box, CACGTG; C-box, GACGTC; and A-box, TACGTA, motifs. These ten different bZIP proteins could be categorized into three groups according to their qualitative and quantitative specificity for G-box and C-box elements. Dissociation constant values (Kd values) of these bZIP proteins for high affinity G-box and C-box elements and reciprocal competition gel mobility shift assays confirmed our classification scheme. Group 1 proteins exhibit a stronger binding affinity for G-box elements, group 2 proteins bind both G-box and C-box motifs with comparable binding affinity, whereas the group 3 proteins display a stronger binding affinity for C-box oligonucleotides. Studies using a panel of G-box and C box oligonucleotides differing in their flanking sequences identified high affinity binding sites. All ten plant bZIP proteins examined, except TGA1a, exhibited type A G-box binding activity preferring class I G-box elements. In contrast to the situation observed for G-box elements, C-box motifs displayed a very much more stringent flanking nucleotide requirement for binding activity. Protein/DNA binding experiments using scanning mutants of a high affinity G-box element and G-box/C-box hybrid elements demonstrated that bZIP protein binding activity depends upon the affinity of protein dimer subunits for ACGT half-sites. Information provided by our systematic analysis of plant bZIP DNA binding specificity can be used to identify high affinity binding sites for the plant bZIP proteins studied here. Assuming that only high affinity bZIP binding sites are likely to function in vivo, identification of these sites will allow us to predict which genes are activated by a particular bZIP protein. PMID- 8487299 TI - Site-directed mutagenesis of the yeast mitochondrial ADP/ATP translocator. Six arginines and one lysine are essential. AB - The ADP/ATP translocator mediates adenine nucleotide exchange across the inner mitochondrial membrane. ADP/ATP exchange is essential when yeast are grown on a non-fermentable carbon source such as glycerol, but it is not required for growth on glucose. Failure to grow on glycerol is therefore a phenotypic indicator of protein function, and it has been used here to screen site-directed mutants to identify functionally important amino acids in the yeast adenine nucleotide translocator (AAC2). Single mutations of all four charged amino acids in the transmembrane segments of AAC2 (K38A, R96D, R96H, R96L, R96P, R204L, R294A) resulted in loss of function, as did mutations in the matrix arginine cluster (R252I, R253I, R254I). Seven other residues were mutated without affecting growth on glycerol (C73S, C244S, C271S, K179M, K182I, P247G, W235F). The non-functional mutants have been used to select intragenic suppressors to gain further insight into the structure of this membrane transport protein. PMID- 8487300 TI - Refined crystal structure of the catalytic domain of dihydrolipoyl transacetylase (E2p) from Azotobacter vinelandii at 2.6 A resolution. AB - Dihydrolipoyl transacetylase (E2p) is both structurally and functionally the central enzyme of the pyruvate dehydrogenase multienzyme complex. The crystal structure of the catalytic domain, i.e. residues 382 to 637, of Azotobacter vinelandii E2p (E2pCD) was solved by multiple isomorphous replacement and refined by energy minimization procedures. The final model contains 2182 protein atoms and 37 ordered water molecules. The R-factor is 18.7% for 10,344 reflections between 10.0 and 2.6 A resolution. The root-mean-square shift deviation from the ideal values is 0.017 A for bond lengths and 3.3 degrees for bond angles. The N terminal residues 382 to 394 are disordered and not visible in the electron density map, otherwise all residues have well-defined density. The catalytic domain forms an oligomer of 24 subunits, having octahedral 432 symmetry. In the E2pCD crystals, the 24 subunits are related by the crystallographic symmetry. The cubic arrangement of subunits gives rise to a large hollow cube with edges of 120 A. The faces of the cube have pores of diameter of 30 A. The true building block of the cube is the E2p trimer, eight of which occupy the corners of the cube. Two levels of intermolecular contacts can be distinguished: (1) the extensive interactions between 3-fold related subunits leading to a tightly associated trimer; and (2) the interactions along the 2-fold axis leading to the assembly of the trimers into the cubic 24-mer. Each subunit has a topology similar to chloramphenicol acetyltransferase (CAT) and comprises a central beta-sheet surrounded by five alpha-helices. The comparison of the two proteins indicates a large rotation of the N-terminal residues 395 to 426 of E2pCD, which reshapes the substrate binding site and extends the interaction between threefold related subunits. The catalytic centre consists of a 30 A long channel extending from the "inner" side of the trimer to the "outer" side, where inner and outer refer to the position in the 24-meric cubic core of the pyruvate dehydrogenase complex and correspond with CoA and lipoamide binding sites, respectively. The active site is formed by the residues with the lowest mobility as indicated by the atomic B factors. Five proline residues surround the active site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487301 TI - Three-dimensional structure of lipoamide dehydrogenase from Pseudomonas fluorescens at 2.8 A resolution. Analysis of redox and thermostability properties. AB - The structure of Pseudomonas fluorescens lipoamide dehydrogenase, a dimeric flavoenzyme with a molecular mass of 106,000 daltons, was solved by the molecular replacement method and refined to an R-factor of 19.4% at 2.8 A resolution. The root-mean-square difference from ideal values for bonds and angles is 0.019 A and 3.8 degrees, respectively. The structure is closely related to that of the same flavoprotein from Azotobacter vinelandii. The root-mean-square difference for 932 C alpha atoms is 0.64 A, with 84% sequence identity. The residues in the active site are identical, while 89% of the interface residues are the same in the two enzymes. A few structural variations provide the basis for the differences in thermostability and redox properties between the two homologous proteins. Particularly, in the A. vinelandii molecule a threonine to alanine (T452A) mutation leaves a buried carbonyl oxygen, located at the subunit interface and in proximity of the flavin ring, unpaired to any H-bond donor, probably providing an explanation for the lower stability of the A. vinelandii enzyme with respect to the P. fluorescens enzyme. Six surface loops, which previously could not be accurately positioned in the A. vinelandii structure, are well defined in P. fluorescens lipoamide dehydrogenase. On the basis of the P. fluorescens structure, the six loops could be correctly defined also in the A. vinelandii enzyme. This is an unusual case where similar refinement methodologies applied to two crystal forms of closely related proteins led to electron density maps of substantially different quality. The correct definition of these surface residues is likely to be an essential step for revealing the structural basis of the interactions between lipoamide dehydrogenase and the other members of the pyruvate dehydrogenase multienzyme complex. PMID- 8487302 TI - Refinement of recombinant oncomodulin at 1.30 A resolution. AB - A refinement of the oncomodulin crystal structure at 1.30 A resolution has been carried out with X-ray data from the recombinant protein. The crystallographic R factor values are 0.169 for 19,995 reflections in the range 6.0 to 1.30 A, which were used for the restrained least-squares refinement, and 0.176 for 20,186 observed reflections in the range 10.0 to 1.30 A. This high resolution refinement has enabled us to make more definitive statements about the molecular structure than was possible heretofore. The present model includes residues 1 to 108, the two Ca2+ of the CD and EF loops, two intermolecular Ca2+, and 103 water molecules per oncomodulin molecule. The electron density maps indicate disordered orientations for ten residues on the hydrophilic surface of the molecule. The pattern of molecular aggregation via intermolecular Ca2+, which occurs in the native rat oncomodulin structure, is also present in the recombinant oncomodulin structure. The Cys18 side-chain is not in a position that would be easily accessible for molecular dimerization via a disulphide bond. The substitution of Glu59, which is preserved in all the determined species of parvalbumin, by Asp59 in oncomodulin seems to break a stabilizing hydrogen bond in the CD loop and render the main-chain in positions 59 to 60 somewhat unstable. This instability in the CD loop, and the strong tendency of oncomodulin for molecular aggregation via intermolecular Ca2+, appear to be the two outstanding features that may account for oncomodulin's biological peculiarities. PMID- 8487303 TI - Crystal structures of holo and apo-cellular retinol-binding protein II. AB - Apo and holo-cellular retinol-binding protein II have been crystallized, and their crystal structures have been determined to 2.1 A and 1.9 A respectively. The apo and holo-crystals have different but related triclinic space groups. The X-ray phases for both structures were determined using the molecular replacement method. The crystal co-ordinates were refined to an R-factor of 0.200 for apo, and 0.173 for holo-cellular retinol-binding protein II. The holo and apo-models have nearly the same tertiary structures. Cellular retinol-binding protein II consists of a ten-stranded anti-parallel beta-barrel with the ligand binding cavity within the barrel. Two alpha-helices cover the open end of the beta-barrel making it almost solvent inaccessible. A single portal large enough to admit a water molecule was observed opening into the binding cavity. Exogenously added retinol was found within the cavity of each holo-cellular retinol-binding protein II molecule. Each retinol was surrounded by both polar and non-polar residues. The hydroxyl group of the bound retinol hydrogen bonds to the amide group of glutamine 108. The overall conformation of the bound retinol was derived from the four different molecules of holo-cellular retinol-binding protein II present in the triclinic form. The four copies of bound retinol had essentially the same conformation as found in crystalline retinaldehyde. PMID- 8487304 TI - Energetics of a stable intramolecular DNA triple helix formation. AB - We have designed and synthesized by conventional chemical techniques a 38mer oligonucleotide consisting of a 5'd(Pu)10d(C)4d(Py)10d(T)4d(Py)10(3') sequence. This oligonucleotide assumes a randomly coiled conformation at pH 12. At pH 8.0 a hairpin helix forms between its 5' purine decamer sequence and the consecutive pyrimidine decamer leaving the second pyrimidine decamer as a dangling disordered 3' extension. On reducing the pH to 4.5 this second pyrimidine decamer folds back onto the major groove of the hairpin helix resulting in an intramolecular triple stranded stem-loop structure. We have used a variety of biochemical (gel mobility, P1 nuclease digestion) and biophysical (ultraviolet light and circular dichroism spectroscopy, fluorimetry, microcalorimetry) techniques to characterize the different conformers, their stability and the folding pathway into an intramolecular triple helix. The thermodynamic properties of this intramolecular triple strand in 100 mM-Na+ are: tm, 71 degrees C; delta HvH, 119.4(+/- 11.9) kcal mol-1; delta Hcal, 121.9 (+/- 6.1) kcal mol-1 at pH 4.5; those of the hairpin are: tm, 63 degrees C; delta HvH, 71.7(+/- 4.0) kcal mol-1; delta Hcal, 69.9(+/- 3.5) kcal mol-1 at pH 8.0. At intermediate pH values, the triplex to coil transition breaks up into its component triplex to hairpin and hairpin to coil transitions with thermodynamic properties: tm, 41 degrees C; delta HvH, 58.7(+/- 4.2) kcal mol-1; delta Hcal, 39.8(+/- 2.0) kcal mol-1; and tm, 63 degrees C; delta HvH, 71.7(+/- 4.0) kcal mol-1; delta Hcal, 69.6(+/- 3.5) kcal mol-1 at pH 6.7. PMID- 8487305 TI - A mutagenic study of the allosteric linkage of His(HC3)146 beta in haemoglobin. AB - We have examined the contribution of His(HC3)146 beta to the alkaline Bohr effect of human haemoglobin (HbA) by replacing it with Gln, using site-directed mutagenesis, and studying the structural and functional consequences. Oxygen equilibrium curves of the mutant show that the effect of pH on the oxygen affinity, the alkaline Bohr effect, is half that of HbA in the presence of chloride ion and less than 10% in its absence. Crystallographic analysis shows that the mutation introduced only small structural changes localized to the site of substitution, proving that the replacement of the hydrogen bond between the ionizable side-chain of His146 beta and Asp94 beta by a hydrogen bond between the unionizable side-chain of Gln146 beta and the same aspartate is solely responsible for the reduction of the alkaline Bohr effect. Our data confirm that His(HC3)146 beta is predominantly responsible for the chloride-independent component of the alkaline Bohr effect which results from the breaking of the hydrogen bond between His(HC3)146 beta and Asp(FG1)94 beta accompanying the transition from the quaternary deoxy to oxy-structure. PMID- 8487306 TI - The in vivo glycation of diabetic tendon collagen studied by neutron diffraction. AB - Glycation (non-enzymatic glycosylation) sites in the axial unit cell of diabetic tendon collagen were investigated by neutron diffraction. Samples of diabetic and control tendon were reacted with sodium borodeuteride and sodium cyanoborodeuteride. This facilitated deuteration at aldimine, aldol or ketoimine groups in the molecule. These are natural collagen cross-links and sites where non-enzymatic glycation had occurred. The introduction of a deuteron at specific locations allowed the diabetic glycation collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. Neutron diffraction was conducted at the Institut Laue Langevin, Grenoble. Standard crystallographic refinement techniques (modified for axial projections) were used to determine the structure of the control (non-diabetic) and diabetic samples. The results are shown as difference maps, these indicate that glycation takes place at different rates within the collagen axial unit cell. The position of glycation correlates well with the position of hydroxylysine residues. The reactions of periodate with enzymatically attached sugars, proteoglycan, natural cross-links and glycation products lead to complications in map interpretation. PMID- 8487307 TI - Primary structure and crystallization of orotate phosphoribosyltransferase from Salmonella typhimurium. AB - Orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10) catalyzes phosphoribosyl group transfer between alpha-D-5-phosphoribosyl-1-pyrophosphate and orotate to form orotidine-5'-monophosphate and pyrophosphate, the nucleotide-forming step in pyrimidine biosynthesis. It is one of ten PRTases that perform vital roles in de novo and salvage pathways for purine, pyrimidine and pyridine nucleotides. Although the PRTases are important drug targets, they are poorly understood mechanistically, and no three-dimensional structures exist. Here, we report the complete sequence of the Salmonella typhimurium pyrE gene and the deduced sequence of the OPRTase gene product. OPRTase forms tetragonal crystals from polyethylene glycol solutions; these crystals diffract to better than 2 A resolution, and are stable to radiation damage. The space group is P4(1)2(1)2 (or P4(3)2(1)2) with unit cell dimensions of a = b = 48.5 A, c = 210.5 A, and alpha = beta = gamma = 90 degrees. A crystalline form of the selenomethionine derivative of the protein is also reported. PMID- 8487308 TI - Crystals of protein L30 from the 50 S ribosomal subunit of Thermus thermophilus. Preliminary crystallographic data. AB - Crystals have been obtained of protein L30 from the large ribosomal subunit of an extreme thermophile, Thermus thermophilus, using ammonium sulphate as a precipitant. The crystals belong to space group P3(1)12 with cell parameters a = b = 64.2 A, c = 78.3 A. They diffract X-rays to at least 2.3 A resolution. PMID- 8487309 TI - New crystal form of the photosynthetic reaction centre from Rhodobacter sphaeroides of improved diffraction quality. AB - Trigonal crystals of photosynthetic reaction centres from the wild-type purple bacterium, Rhodobacter sphaeroides (ATCC 17023), have been grown from potassium phosphate solutions at 18 degrees C. They belong to the space group P3(1/2)21 and have unit cell dimensions of a = b = 141.4 A and c = 187.2 A. The crystals diffract to at least 2.65 A resolution and are suitable for detailed structural studies. PMID- 8487310 TI - Crystallization and preliminary X-ray studies of a protease from Pseudomonas aeruginosa. AB - A protease produced by Pseudomonas aeruginosa has been crystallized by the vapor diffusion method using polyethylene glycol 4000 as a precipitant. The crystals belong to the hexagonal space group P6(1) (P6(5) with unit cell dimensions; a = b = 106.9 A, c = 96.9 A. There are two molecules per asymmetric unit. The crystals diffract X-rays to at least 3.0 A and are suitable for X-ray crystallographic studies. PMID- 8487311 TI - Purification and crystallization of human cyclin-dependent kinase 2. AB - The major transitions of the eukaryotic cell cycle are triggered by cyclin dependent protein kinases. We report the purification and crystallization of the catalytic subunit of human cyclin-dependent kinase 2 (CDK2), which has been implicated in the control of the G1/S transition. CDK2 was purified in large quantities from insect cells infected with a recombinant baculovirus, and crystals of the protein were prepared and subjected to preliminary X-ray diffraction analysis. PMID- 8487312 TI - Cataract surgery. AB - 1. The eye is made up of three layers: the retina, uveal tract, and sclera, which is continuous with the cornea. 2. Drugs are used during surgery to achieve specific effects. Nonsteroidal anti-inflammatory drugs reduce irritation and maintain the dilation effect of cycloplegics and mydriatics. Viscoelastic substances protect the nonregenerative endothelial cells. 3. The risks involved with cataract surgery include hemorrhage in the anterior chamber, a tear in the posterior capsule, and damage to the endothelial cells and retina. PMID- 8487313 TI - Mobile eye units in the fight against eye disease in East Africa. AB - 1. Trachoma is one of the leading causes of blindness in Kenya, but it may be prevented in the early stages by tetracycline ointment. Mobile eye units (MEUs) provide the means by which technicians travel to remote villages. 2. Ophthalmic clinical officers travel to remote areas, providing examinations, diagnoses, ointments, eye medications, and lectures on eye care. In addition, villagers are trained in basic health and hygiene to help prevent many eye disorders. 3. Once the MEUs are purchased, continuing funds are needed to keep them running and to supply them with gasoline. PMID- 8487314 TI - Use of cold spray for relieving pain from local anesthetic injections in ocular surgery. AB - To relieve pain from local anesthetic injections, the authors tried lowering the skin surface temperature by spraying a commercially available cold spray immediately before the injections. A noncontact thermometer was used to measure the thermal change of the skin surface. An esthesiometer was applied to determine the surface perception of the skin. Our basic experiments indicated that there was a relationship between the thermal change and the perception. When the surface temperature dropped to 10 degrees C, there was a definite decrease in the perception. Based on these findings, the authors applied the spray to 100 patients undergoing cataract surgery prior to both akinesia and retrobulbar anesthesia at a distance of 10 cm from the skin surface for 2 seconds, to be immediately followed by the injections. We found the spray to be effective in decreasing the pain due to these injections. Furthermore, there has been no major complications of the spray. PMID- 8487316 TI - Managing contact lens noncompliance. PMID- 8487315 TI - A 5-month-old black boy presented with leukocoria and a "glassy look" in his right eye: Coats' disease. PMID- 8487317 TI - OSHA regulations on universal precautions: a sample training curriculum. AB - 1. Training must be provided to each newly hired employee before that employee can work in a risk environment. Current staff must be trained annually, and additional training must be provided when infection control or universal precaution techniques are revised. 2. Training should include written material, oral presentations, films, videos, computer programs, and audio tapes at the employee's educational, literacy, and language level. Interactive discussion between the trainer and employees is required. 3. Employee evaluation should consist of written pretraining and posttraining tests and a practical demonstration of steps to protect against infectious diseases in the workplace. PMID- 8487318 TI - Dietary fat and breast cancer: where are we? PMID- 8487319 TI - Sex after chemo: a neglected issue. PMID- 8487320 TI - Evidence emerges: colorectal screening reduces deaths. PMID- 8487321 TI - Studies link familial breast, prostate cancers. PMID- 8487322 TI - Cancer rehabilitation. AB - An important trend in cancer treatment is an increasing emphasis on the overall outcome, not just on survival or disease-free interval, but also on the functional status and the quality of life of the survivor. Measuring the quality of life as a part of a clinical protocol is not enough. Measures must be aimed at facilitating optimal function and life satisfaction for the patient treated for cancer. The rehabilitation techniques used to enhance the life of the survivor need to be subjected to the same sort of scientific rigor required for other kinds of treatment. To develop data on rehabilitation parameters, we must create and utilize standardized and reliable evaluation techniques and instruments. These evaluation practices can then be utilized in clinical trials, both to assess the effectiveness of the rehabilitation techniques themselves and also to determine the effect of specific antitumor treatments on the patient's physical and psychosocial function. An organized multidisciplinary cancer rehabilitation program as a part of clinical and research facilities may be helpful. The important concept for all of us involved with the care of cancer patients is that of conveying our concern, not only for their survival, but for their function- physical, emotional, social, and vocational. PMID- 8487323 TI - Fatty acid composition of the subcutaneous adipose tissue and risk of proliferative benign breast disease and breast cancer. AB - BACKGROUND: Studies in animals and geographic correlations across populations suggest that fatty acid intake may have a positive relationship with breast cancer risk, but analytic epidemiologic studies of fat intake have been less supportive. Adipose tissue analysis provides a more objective assessment of intakes of fatty acids that are not endogenously synthesized than do the questionnaire survey methods used in many epidemiologic studies. PURPOSE: This case-control study of postmenopausal women was designed to examine the relationship between fatty acid composition of subcutaneous adipose tissue and risk of breast cancer and proliferative benign breast disease. In addition, we examined specific hypotheses that breast cancer risk is negatively associated with long-chain N-3 fatty acid intake, positively associated with trans fatty acid intake, and positively associated with increased intake of polyunsaturated fat together with low intake of antioxidants. METHODS: Aspirates of subcutaneous fat from the buttocks were obtained from 380 women with newly diagnosed stage I or II breast cancer and 176 with proliferative benign breast disease. A total of 397 women who were evaluated for breast abnormalities at the same institutions but did not require breast biopsy or whose biopsy revealed nonproliferative benign breast disease served as the control group. We examined associations between saturated, monounsaturated, polyunsaturated, trans, or long-chain N-3 fatty acids and breast cancer, atypical hyperplasia, or proliferative benign breast disease without atypia. RESULTS: We observed no consistent patterns of association between breast cancer risk and any of the categories of fatty acids or the individual constituent fatty acids in the adipose tissue. Saturated fatty acids were inversely associated with risk of proliferative benign breast disease without atypia but not with atypical hyperplasia or breast cancer. This association was not observed, however, when total fat intake was taken into account. Women with high levels of polyunsaturated fatty acids in adipose tissue and low serum or dietary levels of antioxidants were not observed to be at higher risk of breast cancer. CONCLUSIONS: Using an objective measure of intake, we observed no major associations between polyunsaturated fatty acids, including long-chain N-3 fatty acids and trans fatty acids, and risk of breast cancer or proliferative benign breast disease. IMPLICATIONS: These data do not support the hypothesis that intake of specific fatty acids, particularly polyunsaturated and trans fatty acids, is an important risk factor for malignant or benign breast disease. PMID- 8487324 TI - Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. AB - BACKGROUND: Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure. PURPOSE: This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin). METHODS: We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy. RESULTS: The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In addition, rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities (P < or = .05). The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis (P < .05) and diarrhea (P = .05) in the rHuEPO-treated group. CONCLUSIONS: We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer. PMID- 8487325 TI - Investigation of the mechanism of tamoxifen-stimulated breast tumor growth with nonisomerizable analogues of tamoxifen and metabolites. AB - BACKGROUND: The nonsteroidal anti-estrogen tamoxifen (TAM) is the front-line endocrine treatment for breast cancer, but disease recurrence is common. Treatment failure may occur because tumors become insensitive to TAM. Alternatively, resistance may occur because tumors become stimulated rather than inhibited by TAM. TAM-stimulated growth of MCF-7 human breast tumors has been observed in athymic mice after prolonged treatment with TAM. PURPOSE: Our purpose was to examine the mechanism of treatment failure by determining whether TAM stimulated tumors acquire the ability to excrete TAM and its anti-estrogenic metabolites or to convert them to estrogenic compounds with weakened antiestrogenic activity. METHODS: We used high-pressure liquid chromatography to quantitate TAM and its metabolites in serum and tumors from ovariectomized athymic mice and in MCF-7 cells grown in vitro. We treated tumor-bearing mice with subcutaneous sustained-release preparations of estradiol, TAM, or a nonisomerizable (fixed-ring) analogue and then assessed the activity of these compounds on TAM-inhibited parental MCF-7 tumors and on TAM-stimulated MCF-7 TAM tumors. RESULTS: We found negligible differences in intratumoral TAM levels between TAM-inhibited parental MCF-7 tumors and TAM-stimulated MCF-7 TAM variants. We did not detect metabolite E (Met E), an estrogenic TAM metabolite, in serum or tumors. Using MCF-7 cells in vitro, we determined that the (Z) isomer of Met E, the form directly produced by TAM metabolism, must be present in the cell at a concentration of over 1000 ng/g to overcome growth inhibition by physiological levels of TAM and antiestrogenic metabolites, but the (E) isomer of Met E was effective at 10 ng/g. We reasoned that conversion of Met E from the (Z) (a weak estrogen) to (E) isomer (a potent estrogen) would be required if formation of Met E were responsible for TAM-stimulated growth. However, fixed ring TAM, which can only form (Z) Met E, was shown to be as capable as TAM of initiating and maintaining anti-estrogen-stimulated growth of MCF-7 tumors in athymic mice. CONCLUSION: Metabolism and isomerization of TAM to estrogenic compounds is not the mechanism of TAM-stimulated growth in our model. IMPLICATION: Other potential mechanisms for TAM-stimulated growth, such as estrogen receptor mutation, must be investigated so that effective strategies can be devised to control breast cancer once therapy fails. PMID- 8487327 TI - Assessment of the carcinogenic potential of chlorinated water: experimental studies of chlorine, chloramine, and trihalomethanes. AB - BACKGROUND: Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts. PURPOSE: The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice. METHODS: Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 x C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 mice. Chlorine or chloramine was administered daily in the drinking water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day. The trihalomethanes were administered by gavage in corn oil at doses ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks. RESULTS: The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results with the trihalomethanes, administration of chlorine or chloramine did not cause a clear carcinogenic response in rats or mice after long-term exposure. CONCLUSION: These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water. PMID- 8487326 TI - Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes. AB - BACKGROUND: Alkylating agents administered as single agents or in combination with antimetabolites or anthracyclines delay the appearance of metastases and prolong the survival of breast cancer patients after surgery. PURPOSE: This phase III clinical trial was designed to evaluate the therapeutic efficacy and toxicity of the alkylating agent cyclophosphamide in combination with the antimetabolites methotrexate and fluorouracil adjuvant to breast cancer surgery. METHODS: This study consisted of 255 breast cancer patients (a) with one to three histologically positive axillary lymph nodes and either no detectable primary tumor or operable primary tumors 5 cm or less (T0-T2) (95% of the patients) or (b) with tumors larger than 5 cm (T3) and with negative axillary nodes. Patients were randomly allocated to receive either methotrexate (60 mg/m2) and fluorouracil (600 mg/m2) (MF) intravenously on days 1 and 8 every 28 days for eight cycles or cyclophosphamide (100 mg/m2) orally on days 1-14 plus MF (CMF) every 28 days for the same duration. Median follow-up was 7.8 years, and maximum follow-up was 13 years. RESULTS: There were no statistically significant differences in time to treatment failure or overall survival for patients treated with MF or CMF. At 8 years after completion of treatment, time to treatment failure was 55% (95% confidence interval [CI] = 50%-60%) and 59% (95% CI = 54% 64%) and overall survival was 69% (95% CI = 65%-73%) and 67% (95% CI = 62%-72%) for MF- and CMF-treated patients, respectively. The hazard ratios (MF to CMF) for time to treatment failure and for survival, estimated with a proportional hazards model, were 1.02 (95% CI = 0.69-1.50) and 0.87 (95% CI = 0.56-1.34), respectively. Myelosuppression was significantly greater (P < .0001) in CMF treated patients during cycles 1-6. Median white blood cell count nadirs were between 4.4 x 10(3)/microL and 3.5 x 10(3)/microL in patients receiving MF and between 3.0 x 10(3)/microL and 2.4 x 10(3)/microL in those receiving CMF. Dose reductions were more frequent in CMF-treated patients, which led to statistically significant differences (P < .0001) in amounts of methotrexate and fluorouracil administered. Primary cancers at other sites occurred in 14 patients (5.5%)--six treated with MF and eight treated with CMF. CONCLUSIONS: Our findings suggest that the addition of cyclophosphamide to adjuvant chemotherapy with MF offers no therapeutic advantage but results in increased myelosuppression. IMPLICATIONS: Future trials will define the possible advantages of antimetabolites in adjuvant therapy. Further information will also become available when results of the ongoing National Surgical Adjuvant Breast and Bowel Project trial comparing adjuvant MF to CMF in node-negative breast cancer patients are presented. PMID- 8487328 TI - Phase I clinical trial of recombinant human interleukin-3 combined with carboplatin in the treatment of patients with recurrent ovarian carcinoma. PMID- 8487329 TI - Re: Chemoprevention studies in the community clinical oncology program. PMID- 8487330 TI - Autoregulation of hepatic macrophage activation in sepsis. AB - Endotoxin (LPS)-stimulated macrophages release mediators, such as tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which modulate the function of many different cells. We hypothesize that macrophage regulation is altered in sepsis and that mediators from LPS-stimulated macrophages "autoregulate" their activation state. Alterations in the LPS dose response relationships for inhibition of hepatocyte protein synthesis by hepatic macrophages (hMos) were examined to investigate factors that regulate hMo activation. In vitro pretreatment was compared using TNF alpha, PGE2, subactivating concentrations of LPS, or LPS plus indomethacin. Pre-exposure to LPS resulted in a dose-dependent loss of subsequent LPS-triggered activation of hMos in co-culture. Pretreatment with LPS and 1 mumol/L indomethacin partially restored hMo responsiveness. Pre exposure to PGE2 significantly decreased LPS responsiveness of co-cultured hMos, suggesting that PGE2 produced by LPS-stimulated hMos may mediate this effect. Pretreatment of hMos with TNF alpha, but not IL-1 beta, significantly lowered the LPS concentration required for maximal hMo activation. We conclude that both macrophage mediators and LPS pretreatment alter macrophage activation state. These data suggest an "autoregulatory" role for mediators of LPS-stimulated macrophages in sepsis. PMID- 8487331 TI - Blood component supplementation during massive transfusion of AS-1 red cells in trauma patients. AB - Coagulation component transfusions in trauma patients given more than 10 units of AS-1 red cells during the first 24 hours after injury were studied. Serial coagulation tests were obtained to direct component therapy. Coagulopathy developed in more than 70% of patients. Patients with blunt or penetrating trauma had similar coagulation abnormalities during massive transfusions. More than 40% of patients with either exsanguinating hemorrhage from penetrating trauma or blunt trauma with associated brain injuries had abnormal coagulation tests on admission. In contrast, patients with blunt trauma, but without brain injury, did not have coagulopathy on admission. Patients received an average of 25 units (range, 10-77) of AS-1 red cells and were exposed to an average of 80 (range, 11 252) donors. Exsanguination and brain injuries primarily caused death in 57%. Abnormal coagulation tests will be frequent and profound during a massive transfusion with AS-1 red cells. Serial coagulation testing is recommended. PMID- 8487332 TI - Ultrasound in blunt abdominal and thoracic trauma. AB - Between July 1989 and June 1991, 312 patients with blunt thoracic or abdominal injuries were examined prospectively. Sonographic examination was performed by surgeons in the emergency room using a mobile ultrasound unit. In 113 (36.2%) cases pathologic findings were demonstrated sonographically. These included 47 cases of hemothorax, 11 pericardial effusions, 52 cases of intra-abdominal fluid, 24 lesions of intra-abdominal organs, and 10 cases of retroperitoneal hematoma. Physical examination findings were positive in 96 (30.8%), negative in 63 (20.2%), and equivocal in 153 (49.0%). Two hundred thirty-nine patients had between one and eight injuries in addition to the blunt abdominal or thoracic trauma. These patients had an average Injury Severity Score (ISS) of 19.9 (range, 1 to 75). The 73 patients with isolated blunt trauma of the thorax or abdomen had an ISS of 4.9 (range, 0-25). None of the 66 patients (21.2%) with positive clinical findings and negative sonographic examination results had to be operated on later in the course of treatment, while 5 (36%) of 14 patients (4.5%) with negative physical examination findings and positive sonographic findings had to undergo surgery. The sensitivity for the demonstration of intra-abdominal fluid and organ lesions was 98.1% and 41.4%, respectively. The overall sensitivity and specificity of the ultrasonic examination were 90.0% and 99.5%, respectively. PMID- 8487333 TI - Selective exclusion of the injured lung. AB - Intratracheal bleeding and intrapleural air leakage that are uncontrollable by conventional therapy are life-threatening in patients with blunt pulmonary trauma. Selective exclusion of the injured lung is the most effective treatment in such cases. Two hundred six consecutive patients over a 5-year period with blunt pulmonary trauma who survived 5 hours or more after arriving at the hospital were divided into three categories based on mode of treatment. In 190 (92%), intratracheal bleeding, intrapleural air leakage, and intrapleural bleeding were controllable by conventional treatment (class 1). In six (3%), intratracheal bleeding and intrapleural air leakage were controllable by selective pulmonary exclusion, and intrapleural bleeding was controllable by tube thoracostomy (class 2). In ten (5%), thoracotomy was required because of uncontrollable intratracheal bleeding or intrapleural air leakage, despite selective pulmonary exclusion, or intrapleural hemorrhage was not controllable by tube thoracostomy (class 3). Among the 16 patients with class 2 or 3 trauma, 14 survived. PMID- 8487334 TI - Supracondylar fracture of the femur: closed or open reduction? AB - Fifty-one cases of supracondylar fracture of the femur with a mean follow-up of 29 months were retrospectively studied. Thirty-one fractures were open; most had major soft tissue damage. Open management was used for 32 of the fractures with good to excellent results in 81%, while a good or excellent outcome was attained in only 42% of the 19 fractures treated nonsurgically. Malunion was observed in seven cases treated by closed methods and in only one case treated by open reduction. The patients treated surgically also had shorter average hospital stays and a better range of motion in the knee, while the rates of deep infection (three cases) and nonunion (two cases) were similarly distributed between the surgically and nonsurgically managed groups. Twelve patients required closed knee manipulation to improve knee motion, five in the group treated by closed reduction and seven in the group treated surgically with an average gain in motion of 52 degrees in the former and 42 degrees in the latter group. PMID- 8487335 TI - Emergency cricothyroidotomy in trauma victims. AB - The first dictum of trauma care is to establish an airway. Infrequently endotracheal intubation is unsuccessful or contraindicated, and a surgical airway is required. We reviewed 30 emergency cricothyroidotomies among 8320 admissions over a 36-month period at a level I trauma center. Twenty cricothyroidotomies were performed in the emergency room by Trauma Service personnel and 10 during prehospital care by flight nurses. Cricothyroidotomy was the first airway control maneuver performed in 7 patients and 23 cricothyroidotomies were performed after attempts at oral intubation failed. No major complications were identified. Minor complications identified in the hospital included minimal subglottic stenosis (2), local wound infection (1), and nonthreatening hemorrhage (1). Fifteen patients were long-term survivors. We conclude that emergency cricothyroidotomy is a safe and rapid means of obtaining an airway when endotracheal intubation fails or is contraindicated. PMID- 8487336 TI - The role of diagnostic laparoscopy in the management of trauma patients: a preliminary assessment. AB - This study evaluated the role and advantages of diagnostic laparoscopy (DL) compared with diagnostic peritoneal lavage (DPL) in 75 trauma patients who were prospectively studied with DL followed by DPL. Of these, 59 patients had blunt injuries and 16 stab wounds. Seventy patients (93%) had the procedures performed in the emergency department (ED); 41 (59%) of these were awake and under local anesthesia. Forty-two patients had negative DPL and DL results with no subsequent sequelae. Twenty-three patients had negative DPL results and abnormal DL results. Of these, 20 were managed nonsurgically, and three (DPL < 10,000 RBC) underwent surgery based solely on DL findings of diaphragmatic lacerations from stab wounds. These were repaired. All 23 had an uneventful course. Three patients had positive DPL and insignificant DL findings. Laparotomy and DL findings correlated. A splenectomy for iatrogenic injury unrelated to DL and two nontherapeutic laparotomies were performed. Seven patients demonstrated both positive DPL and significant DL findings, and all had therapeutic laparotomies. Management based on DL rather than DPL would potentially have improved care in 8% of cases (6 of 75). Reliance on DL improved care in 19% (3 of 16) of patients with stab wounds and possibly could have in 3% (2 of 59) of those with blunt injuries. Management using DL would have potentially improved care in 30% (3 of 10) of patients with positive DPL findings and 5% (3 of 65) with negative DPL findings. Diagnostic laparoscopy can be performed safely in stable patients under local anesthesia in the ED. It offers no advantage over DPL as a primary assessment tool in blunt trauma. It does have advantages in the management of stab wounds. Diagnostic laparoscopy has a role in redefining DPL criteria for laparotomy and, in selected patients, as an adjunct to DPL, allowing further diagnosis and potentially the treatment of injuries without laparotomy. PMID- 8487337 TI - Prospective evaluation of surgeons' use of ultrasound in the evaluation of trauma patients. AB - Ultrasound diagnostic imaging has been demonstrated to be a valuable investigative tool in the evaluation of trauma patients in Europe and Japan. In the United States, however, ultrasound has not been widely used by trauma surgeons because of its lack of availability in the trauma resuscitation area and the associated cost and lack of full-time availability of a technician. In this prospective study, four attending trauma surgeons, four trauma fellows (PGY 6 and 7), and 25 surgical residents (PGY 4) at a level I trauma center were trained in specific ultrasound techniques to identify fluid in trauma patients with thoracoabdominal injuries. Their ultrasound evaluations of 476 patients demonstrated that in 90 patients with clinically significant injuries, ultrasound imaging successfully detected injury in 71, for a 79% sensitivity. Specificity was 95.6%. We conclude that (1) surgeons can rapidly and accurately perform and interpret ultrasound examinations; and (2) ultrasound is a rapid, sensitive, specific diagnostic modality for detecting intraabdominal fluid and pericardial effusion. PMID- 8487338 TI - Physical impairment and functional outcomes six months after severe lower extremity fractures. AB - To determine functional outcomes after lower extremity fracture (LEF), a prospective follow-up study of patients admitted to three level I trauma centers for treatment of unilateral LEFs was conducted. In this paper we describe outcomes at 6 months after discharge from the initial hospitalization and examine the relationship between impairment and disability. A total of 444 patients met the entry criteria for the study. Of these 376 (85%) were successfully located and interviewed at 6 months; 302 (68%) returned to the trauma center at 6 months for a clinical assessment by a physical therapist. Study patients were predominantly young (mean age = 32.4), white (72%) men (70%) who were working before the injury (77%). The fractures resulted primarily from motor vehicle crashes (71%); mean hospital LOS was 12 days. Disability was measured using the Sickness Impact Profile (SIP), a well validated patient assessment of health status. The overall SIP score averaged for all patients was 10.2, denoting a moderate level of dysfunction or disability. Analysis of the 12 subscores that constitute the SIP indicate particularly high scores for ambulation (16.7 postdischarge vs. 1.2 preinjury), sleep and rest (14.0 vs. 5.1), emotional behavior (10.5 vs. 2.2), home management (15.1 vs. 2.6), recreation and pastimes (19.0 vs. 4.4), and most notably, work (33.2 vs. 8.3). Further analysis of the subgroup of patients working before the injury shows that 48% had returned to work at 6 months. Correlations between lower extremity impairment (range of motion, muscle strength, and pain) and the ambulation subscore of the SIP were high. However, correlations between impairment and more global areas of activity such as home management, work, and recreation were considerably lower. These results suggest that other factors, over and above the extent of physical impairment, significantly influence broader disability outcomes such as return to work. Further research is needed to define these factors so that effective interventions after acute care can be identified and appropriately targeted. PMID- 8487339 TI - Primary intramedullary femur fixation in multiple trauma patients with associated lung contusion--a cause of posttraumatic ARDS? AB - We investigated whether primary (< 24 hours) intramedullary stabilization of femoral shaft fractures in multiple trauma patients with severe thoracic injury might be associated with an increased incidence of adult respiratory distress syndrome (ARDS). A total of 766 patients with multiple trauma admitted to Hannover Medical School between January 1, 1982, and December 31, 1991, were investigated retrospectively. Of these, 106 patients met the inclusion criteria: Injury Severity Score > 18, femoral midshaft fracture treated by intramedullary nailing, primary admission or referral within 8 hours after injury, and no death from head injury or hemorrhagic shock. Two groups were differentiated according to the presence or absence of chest trauma (severe chest trauma = AIS thorax > or =, group T; no severe chest trauma = AIS thorax < 2, group N). Selection of subgroups according to the time of femur stabilization was group I < 24 hours after trauma, group II > 24 hours after trauma. Injury Severity Scores in the four groups were TI: 29.4 (n = 24); TII 31.4 (n = 26); NI 20.1 (n = 33); NII 25.4 (n = 23). In patients without thoracic trauma the ICU time (NI: 7.3 days; NII: 18.0 days) and intubation time (NI: 5.5 days; NII: 11.0 days) were lower in the patients treated primarily (p < 0.05). In patients with severe chest trauma there was a higher incidence of posttraumatic ARDS (33% versus 7.7%) and mortality (21% versus 4%) when early intramedullary femoral nailing was done. In the absence of severe chest trauma primary intramedullary femoral nailing is beneficial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487340 TI - Head injury and facial injury: is there an increased risk of cervical spine injury? AB - A series of 8285 blunt trauma victims from one hospital were analyzed to establish the possible association of cervical spine injuries with craniocerebral and facial injuries. Patients with clinically significant head injuries were at greater risk of cervical spine injuries than those without head trauma (4.5% vs. 1.1%, significant by Chi-squared analysis). Patients with Glasgow Coma Scale scores of 8 or less were at even greater risk of cervical spine injuries (7.8%). Facial injuries were not associated with cervical spine injuries. Procedures to achieve airway control in patients with serious head injuries must reflect these findings so that protection is afforded to the cervical spine during trauma resuscitation. PMID- 8487341 TI - Long-term consequences of minimal brain injury: loss of consciousness does not predict memory impairment. AB - This study evaluated the memory and intellectual function of 32 adults following minimal brain injury. All patients had a Glasgow Coma Scale score of 15 upon evaluation in the Emergency Room, negative findings on radiographic examination, and negative history of prior neurologic disease or injury. Seventeen of these had experienced a loss of consciousness. Patients suffering a loss of consciousness postinjury obtained significantly lower mean verbal intelligence quotients than those obtained by patients who remained conscious following their accidents. Both groups exhibited memory impairments. This could indicate that loss of consciousness predicts intellectual impairment, but not degree of memory dysfunction. An alternative interpretation of these data is that patients referred for examination after a head injury that did not involve a loss of consciousness included a disproportionate number of patients from upper socioeconomic levels who have greater access to medical delivery systems or greater sophistication regarding cognitive function. PMID- 8487342 TI - The effect of education and safety devices on scald burn prevention. AB - A prospective study was designed to evaluate the effects of education on the incidence of pediatric scald burns. Demographic data from our Trauma Registry identified the Zip code area of greatest risk. Eighty of 121 families with children in a large rental property were chosen randomly for the education program. Twenty of these families also had an anti-scald device installed in the bathtub faucet; all had two or more children under age 5 years. Families were surveyed before and after intervention. Safety knowledge improved post-education as judged by correct survey responses. Although 90% of the families had water heaters set at "warm" (< or = 120 degrees F), the actual temperature at the tap was above 130 degrees F in 71%. The anti-scald devices did work, but at 9 months all but one had been removed because of sediment buildup, which prevented water flow. In the year of the study, the number of scald burns from the target Zip code area decreased from 15 to 12. This was a pilot project for programs that can test public response to general safety education. An anti-scald device in conjunction with education works well in theory, but a better device needs to be engineered. In view of discrepancies between water heater settings and tap water temperature, housing authorities could play a vital role in implementing safety measures. PMID- 8487343 TI - Arterial intimal flaps: a comparison of primary repair, aspirin, and endovascular excision in an experimental model. AB - The optimal management for traumatic arterial intimal injuries is unresolved. Three therapeutic options were compared in an experimental model employing a standard intimal flap created in 51 canine superficial femoral arteries. Group 1 (14 arteries) underwent resection with end-to-end repair. Group 2 (19 arteries) received acetylsalicylic acid (ASA) and observation only. Group 3 (21 arteries) underwent endovascular excision of the flap with angioscopic guidance. Control intimal flaps (18 arteries) were created and observed without further intervention. Patency in group 1 (primary repair) and group 2 (ASA) was 100%; the patency in both was significantly (p < 0.05) greater than in the controls, which was 67%. Patency in group 3 (endovascular excision) was 79%. Residual luminal defects were observed in only 8% of the arteries repaired primarily, but in 76% of the aspirin-treated arteries. Residual luminal defects following endovascular excision were present in 53% of the arteries remaining patent. Although resection and primary repair (group 1) provided better results than observation alone (control), addition of ASA (group 2) also sustained patency. However, a high incidence of residual intimal defects occurred, the natural history of which is unknown. While endovascular excision (group 3) may become a feasible alternative, current technology provided inferior patency with frequent residual intimal defects. These results suggest that observation alone supplemented with antiplatelet medication (ASA) may be adequate treatment, but longer follow-up is necessary for confirmation. PMID- 8487344 TI - Abdominal surgical wound infection is lowered with improved perioperative enterococcus and bacteroides therapy. AB - Perioperative antibiotics decrease surgical wound infection (SWI) in trauma patients requiring abdominal exploration. This investigation evaluated 24 hours of cefoxitin or ampicillin/sulbactam used for early therapy in such patients. Patients were randomly assigned to one of two treatment groups. The primary endpoint evaluated was SWI, which was defined as purulent drainage or active wound treatment. Five hundred ninety-two patients were evaluated: 283 received ampicillin/sulbactam and 309 received cefoxitin. The incidence of wound infection among the ampicillin/sulbactam patients was 2% and among cefoxitin patients it was 7% (p < 0.004). The cefoxitin patients with colon injuries were analyzed (p < 0.007). The major difference between the two groups was an increased incidence of enterococcal infections in the cefoxitin-treated patients. A single broad spectrum antibiotic given for 24 hour perioperatively effectively controls SWI. Use of ampicillin/sulbactam results in a significantly lower SWI rate than use of cefoxitin, which may be a result of improved enterococcal and Bacteroides coverage. PMID- 8487345 TI - Bacterial translocation occurs in humans after traumatic injury: evidence using immunofluorescence. AB - We evaluated the occurrence of bacterial translocation (BT) in humans after traumatic injury. Twenty trauma patients (18 with blunt trauma) requiring celiotomy and without hollow viscus injury were studied. After surgical hemostasis and repair, portal venous blood (PVB) was sampled for culture. Additionally, a mesenteric lymph node (MLN) was harvested for culture and indirect immunofluorescence analysis using, first, mouse monoclonal antibody to E. coli beta-galactosidase, then goat anti-mouse immunoglobulin G (IgG). Injury Severity Score (ISS), Trauma Score (TS), and period of hemorrhagic shock (HS; systolic BP < 90 mm Hg with blood loss > 500 mL) were recorded before specimens were obtained. RESULTS: Fifteen patients initially had HS (mean period of 60 minutes). Mean TS and ISS were 10 and 29, respectively. Seven patients did not have HS (mean TS and ISS, 10 and 13). Three patients received antibiotics preoperatively. Portal venous blood culture produced positive results in only three patients (two with HS) and culture of the MLN specimen was positive in one. However E. coli beta-galactosidase was detected within the cytoplasm of macrophages in all MLNs. One patient developed multiple organ failure. CONCLUSION: Bacterial translocation occurs in humans following traumatic injury and may be independent of HS. Culture techniques may not detect BT since organisms may have been phagocytized by macrophages. The clinical significance of BT in trauma patients remains unclear. PMID- 8487346 TI - A circulating protein that depolarizes cells increases after hemorrhage in dogs. AB - Recent evidence suggests that a circulating factor or factors may mediate cell membrane depolarization after hemorrhage in rats. To test for the presence of a similar factor in dogs, conscious adult splenectomized dogs with chronic arterial cannulae were either (1) bled 30% of measured blood volume over 3 minutes (HEM, n = 8); (2) bled 30% of measured blood volume over 3 minutes and reinfused with the shed blood 10 minutes later (HEM + REINF, n = 6); or (3) observed without hemorrhage (CONTROL, n = 5). Treatments were applied in random order, 72 hours apart. Arterial blood was sampled at rest and for 1 hour. Depolarizing activity of the plasma was measured in an in vitro bioassay using resting dog RBCs and a membrane potential-sensitive oxonol dye (DIBAC). Fluorescence was measured by spectrofluorometry and the percentage of change from resting values was calculated. Fluorescence intensity increased after hemorrhage in the HEM and the HEM + REINF groups. Fluorescence intensity decreased to CONTROL values in the HEM + REINF group by 10 minutes after reinfusion of shed blood, but remained greater than CONTROL values in the HEM group. The magnitude of early cell membrane depolarization was approximately 20 mV. Similar depolarization was observed in cultured canine skeletal myocytes and pre-adipocytes. Changes in fluorescence intensity correlated with changes in mean arterial pressure at all times after hemorrhage except at 15 minutes (5 minutes after reinfusion in the HEM + REINF group). The depolarizing activity in dog plasma after hemorrhage shares several physical chemical properties with a similar substance identified in rats after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487347 TI - Isolated fracture-dislocation of the sacrum: case report. AB - An unusual case of isolated fracture-dislocation of the sacrum is reported. A 19 year-old woman had a fracture-dislocation of S-1-2 combined with two longitudinal fractures of the sacrum, but no other pelvic fractures were identified. The possible mechanisms of fracture-dislocation of the sacrum are discussed. The fracture site was identified accurately on a CT scan. Pain relief was obtained by application of an external fixator. A mild neurologic deficit in the S-1 root distribution disappeared uneventfully. PMID- 8487348 TI - Acute epidural hematoma appearing as a side-by-side isodensity and hyperdensity on computed tomographic scan: case report. AB - A case of acute epidural hematoma appearing as a side-by-side isodensity and hyperdensity on a computed tomographic (CT) scan is presented. This uncommon CT finding is discussed and the pathophysiology is reviewed. PMID- 8487349 TI - Vascular surgery: "a running commentary". PMID- 8487350 TI - Routine surveillance after carotid endarterectomy: does it affect clinical management? AB - PURPOSE: Although routine noninvasive surveillance is recommended after carotid endarterectomy (CEA), there are little data to show that identification and eradication of recurrent carotid artery stenosis are necessary to avoid the risk of subsequent neurologic complications. METHODS: We reviewed our experience over a 16-year period in 380 consecutive patients undergoing 409 CEAs who underwent serial postoperative ultrasonic scanning at 6 weeks, 6 months, and 1 year after CEA and then yearly thereafter. RESULTS: Recurrent stenoses (> or = 50% diameter reduction) were detected in 44 arteries (10.8%) during follow-up from 1 to 177 months (mean 42.0 months). Most (70.5%) occurred within 2 years of CEA. Cumulative recurrence rates were 5.8%, 9.9%, 13.9%, and 23.4% at 1, 3, 5, and 10 years, respectively. Recurrent stenoses were more frequent in female (p = 0.02) and younger patients (p = 0.01) and less frequent in those having a vein patch repair (p = 0.02). Most recurrences (84%) were in the 50% to 79% stenosis range. In four patients 80% to 99% stenoses developed and in three patients total occlusions developed, for a severe recurrence rate of 2.1%. Only 10 (22.7%) of the recurrent stenoses were initially symptomatic, and only one (2.9%) of the asymptomatic restenoses later became symptomatic. One patient with recurrent stenosis suffered a stroke (0.3%). Cumulative 5-year ipsilateral stroke-free rates in patients with recurrent stenosis (94.4%) were practically identical (p = 0.76) to those in patients without recurrent stenosis (94.2%). Life-table ipsilateral stroke-free survival rates at 5 years were 94.2% in patients with recurrent stenosis and 78.4% in patients without recurrent stenosis (p = 0.16). Four (9%) recurrent stenoses and 12 lesions (27%) in the contralateral artery progressed. Only seven patients (1.7%) underwent repeat operation for ipsilateral disease, four for symptoms and three for recurrent stenosis. CONCLUSIONS: Recurrent carotid artery stenosis occurs early after CEA, is typically benign, and remains stable over a prolonged follow-up period. Our results question the importance of routine noninvasive surveillance after CEA and suggest that a more conservative approach would be equally beneficial in terms of clinical relevance and cost-effectiveness. PMID- 8487351 TI - Combined use of duplex imaging and magnetic resonance angiography for evaluation of patients with symptomatic ipsilateral high-grade carotid stenosis. AB - PURPOSE: Advances in cerebral vascular imaging suggest that patients with critical levels of carotid artery stenosis (> 70%) who have symptoms can be identified accurately and necessary information about the intracranial and extracranial circulation obtained before surgery without conventional angiography. We have used carotid duplex imaging in combination with magnetic resonance angiography (MRA) to evaluate 20 patients with symptomatic ipsilateral high-grade carotid stenosis. METHODS: All patients underwent CT and magnetic resonance imaging brain scans, as well as MRA and conventional arteriography of the cerebral circulation. Magnetic resonance angiograms were obtained with two dimensional phase contrast and time-of-flight techniques. Phase contrast was used for intracranial vascular imaging and for determining qualitative flow velocities and the direction of blood flow in the circle of Willis. Two-dimensional time of flight was used to assess the carotid bifurcations. RESULTS: Twenty patients with symptoms (six with strokes, 11 with transient ischemic attacks, and three with amaurosis fugax) had duplex evidence of high-grade carotid stenoses. Computed tomographic and magnetic resonance brain scans were positive for cerebral infarction in six patients with clinical strokes. Comparison of MRA with conventional angiography was 91% accurate for high-grade stenoses and occlusions (sensitivity 100% and specificity 90% for stenosis; sensitivity/specificity was 100% for complete occlusion). Comparison of duplex imaging with conventional angiography demonstrated 86% accuracy for detection of severe stenosis or occlusion (sensitivity 94% and specificity 89% for stenosis; sensitivity and specificity were 100% for complete occlusion). CONCLUSIONS: This study suggests that combined use of MRA and duplex imaging is accurate for detection and evaluation of high-grade carotid stenoses in patients with symptoms. PMID- 8487352 TI - The effect of nifedipine on lipid and monocyte infiltration of the subendothelial space. AB - PURPOSE: Calcium channel blockade has been shown to inhibit experimental atherosclerosis in cholesterol-fed animals, and early clinical trials suggest its benefit in human subjects as well. METHODS: To determine the effect of the calcium channel blocker nifedipine on lipid and monocyte infiltration of the subendothelial space, an endothelial cell (EC)-smooth muscle cell (SMC) bilayer model of the arterial wall was incubated for 18 hours with nifedipine (0.1 micrograms/ml). Iodine 125-labeled low-density lipoprotein (125I-LDL) (10 micrograms protein/ml) was then added to the upper-well medium. RESULTS: After a 3-hour incubation period, nifedipine-treated bilayers showed an increased permeability to LDL (p < 10(-7). Nifedipine had no effect on the membrane binding or cellular uptake of LDL by the EC but did increase SMC binding and uptake (p < 0.0005). U937 monocytes were found to incorporate 125I-LDL in a concentration dependent fashion, without saturation to 25 micrograms/ml, the highest concentration studied. Nifedipine increased monocyte uptake of LDL (10 micrograms/ml; p < 0.003 but reduced monocyte movement through the EC barrier (p < 10(-7). A study of the selective preincubation of each cell type (EC, SMC, and monocyte) with nifedipine indicated that this reduction was likely the result of a direct effect on the monocyte. CONCLUSIONS: Given the potential cytotoxic effects of the monocyte within the subendothelial space, nifedipine-induced inhibition of monocyte infiltration and enhancement of lipoprotein uptake by the SMC may be protective. PMID- 8487353 TI - Optimizing technical success of renal revascularization: the impact of intraoperative color-flow duplex ultrasonography. AB - PURPOSE: Technical problems with renal revascularization can be difficult to detect, especially with end points of transaortic renal endarterectomies or anastomosis of bypass grafts to small distal renal arteries. If missed, such technical mishaps may not be recognized until after operation, when the chance for timely renal salvage has often been lost. METHODS: To evaluate the value of newer color-flow duplex imaging, we performed intraoperative ultrasonography on 35 patients undergoing revascularization of 64 renal arteries, 29 patients undergoing transaortic endarterectomy, and 6 undergoing bypass grafting. Most patients (24/35; 69%) underwent concomitant aortic reconstruction. Ninety-four percent had hypertension, whereas 66% had associated chronic renal insufficiency. RESULTS: Technical abnormalities prompting operative revision were identified during surgery in 10.9% of reconstructed main renal arteries (7/64). These included two occlusions, three intimal defects, and one extrinsic tissue band after endarterectomy plus one graft anastomotic stenosis. Color-flow imaging revealed all of them. Technical defects were also associated with higher peak systolic flow velocities (mean 2.62 m/sec; range 2.00 to 3.50 m/sec) than normal appearing arteries (mean 1.34 m/sec; range 0.40 to 2.50 m/sec) (p = 0.004). Eighty-six percent of the defects (6/7) were immediately correctable. One patient required nephrectomy. Postoperative angiograms revealed two asymptomatic small branch-vessel occlusions (3%). Compared with preoperative levels (p < 0.01), both hypertension and renal insufficiency improved initially. The clinical outcome of patients requiring intraoperative revision did not differ from that of patients undergoing normal intraoperative studies. CONCLUSION: Intraoperative color-flow duplex detection and surgical correction of technical problems with renal revascularization have enhanced our technical success and been associated with long-term results comparable to those of patients undergoing normal intraoperative studies. PMID- 8487354 TI - Increased platelet-derived growth factor production and intimal thickening during healing of Dacron grafts in a canine model. AB - PURPOSE: Growth factor production by endothelial cells on grafts may play a role in the development of intimal hyperplasia and subsequent graft failure. METHODS: To study the relationship between platelet-derived growth factor production and graft healing, 26 beagles underwent placement of 20 cm long, 6 mm internal diameter, knitted Dacron thoracoabdominal grafts, either seeded with autologous endothelial cells (n = 14) or unseeded controls (n = 12). The grafts and adjacent arteries were removed 4 or 20 weeks after implantation for measurement of platelet-derived growth factor production in organ culture, endothelial cell coverage, and intimal thickness. RESULTS: Midgraft platelet-derived growth factor production by seeded graft segments increased from 41 +/- 6 to 148 +/- 27 pg/cm2/72 hr (p < 0.002) between 4 and 20 weeks. This was accompanied by a significant increase in inner-capsule thickness. Platelet-derived growth factor production by control graft segments also increased from 58 +/- 21 to 163 +/- 42 pg (p < 0.05) and was similar to that of seeded grafts despite more rapid endothelialization of seeded grafts. The increase in growth factor production by Dacron grafts was greater than that of the expanded polytetrafluoroethylene grafts studied previously despite similar endothelial cell coverage. CONCLUSION: This increase corresponded with the rapid appearance of smooth muscle cells in the pseudointima of Dacron grafts, suggesting that these cells may be responsible for the observed increase in platelet-derived growth factor production. PMID- 8487355 TI - Supraceliac aortic cross-clamping: determinants of outcome in elective abdominal aortic reconstruction. AB - PURPOSE: A 7-year experience in which 43 patients underwent supraceliac aortic cross-clamping (SC-AXC) during elective abdominal aortic reconstruction was reviewed. METHODS: Operation was performed for abdominal aortic aneurysm (AAA) in 29 (68%) patients, aortoiliac occlusive disease in seven (16%), proximal anastomotic AAA in three (7%), "shaggy" aorta syndrome in three (7%), and in situ grafting of a previously ligated aorta in one (2%) patient. The indications for supraceliac control included pararenal AAA origin (25), pararenal aortic atherosclerosis (18), inflammatory AAA (2), and a short infrarenal aortic stump (1). Vital organ ischemic complications (VOICs) were defined as any major ischemic complication involving the liver, kidneys, bowel, or spinal cord. RESULTS: The incidence of VOICs was significantly increased when concomitant renal or visceral revascularization (CRVR) was required (p = 0.002) and correlated with an increasing SC-AXC time (p = 0.015). In patients undergoing CRVR (n = 16) the perioperative mortality rate was 25%; VOICs developed in six patients and included renal failure (3), mesenteric/colonic ischemia (3), hepatic ischemia with coagulopathy (2), and spinal cord ischemia (1). In contrast, in those not requiring CRVR (n = 27), SC-AXC was well tolerated. There were no VOICs and no deaths; morbidity rate was 33%. CONCLUSIONS: The incidence of VOICs associated with the use of SC-AXC is primarily related to the level of preoperative renal or mesenteric insufficiency, the severity of pararenal aortic atherosclerosis, the extent of the operative procedure, and the duration of proximal aortic cross-clamping. In complex abdominal aortic reconstruction in which infrarenal aortic control is either not possible or deemed hazardous, SC AXC is a safe and valuable technique for achieving proximal control. PMID- 8487356 TI - Pharmacologic modulation of intimal hyperplasia in canine vein interposition grafts. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of three drugs (cilazapril, cyclosporine, and aspirin) in modulating the progression of intimal hyperplasia during short postoperative times in short-segment, autogenous vein bypass grafts in a canine model. The relative effects of the drugs on the progression of intimal hyperplasia were compared with the Gilman parameter, a measure used extensively as a wound healing descriptor. To our knowledge this is the first use of the Gilman parameter in assessing vascular disease. METHODS: Seventy-two conditioned mongrel dogs were randomly and equally divided according to a three-factor analysis of variance. The factors included (1) drug treatments (cilazapril [10 mg/kg/day], cyclosporine [4 mg/kg/day], aspirin [325 mg/day], and control [nonmedicated]), (2) implantation sites (femoral and carotid arteries), and (3) postoperative times of graft harvest (1, 3, and 6 weeks). Each dog had 2 cm segments of autogenous jugular vein interpositioned bilaterally into each of the paired carotid and femoral arteries. Quantitative data on luminal narrowing over time from intimal hyperplasia were compared from calculated Gilman parameters after image analysis of retrieved, histologically processed graft sections. RESULTS: The observed variability in the data was attributed to drug treatments and time. At 1 week after operation the mean Gilman parameters did not differ significantly among the treatment groups in either midgraft or distal graft segments. At 3 weeks the mean Gilman parameters of midgraft and distal graft sections of cyclosporine-treated dogs differed significantly (p < 0.05) from those of the control group and the cilazapril and aspirin-treated groups, which did not differ from each other. At 6 weeks after operation, mean Gilman parameters from aspirin- and cyclosporine-treated dogs differed statistically from control and cilazapril-medicated dogs and from each other (p < 0.001). CONCLUSIONS: These data support the efficacy of aspirin and cyclosporine in reducing intimal hyperplasia in short-segment arterialized vein grafts during short postoperative periods. Additional studies are required to ascertain whether the beneficial effects of aspirin and cyclosporine persist long-term. PMID- 8487357 TI - A reevaluation of intraarterial thrombolytic therapy for acute lower extremity ischemia. AB - PURPOSE: This study was performed to clarify the role of intraarterial thrombolytic therapy (IATT) in the management of acute lower extremity ischemia. METHODS: A retrospective review of 77 patients undergoing 84 courses of high-dose regional urokinase IATT from July 1981 to June 1991 was performed. The group included patients with acute thrombosis of lower extremity bypass grafts (n = 48) or native arteries (n = 36), presenting with ischemic but viable limbs, minimal or no motor dysfunction, and an absence of muscle rigor or compartment syndrome. The data were then examined individually by site of thrombosis to evaluate patient selection for IATT. RESULTS: Complete lysis, complications (either distal thromboembolism or bleeding), and early limb loss occurred in 59.5%, 11%, and 6% of infusions, respectively. IATT precluded the need for operative intervention in 49% of acutely ischemic limbs. When surgery was required, successful IATT precisely localized responsible lesions and reduced the magnitude of operation. A subset of 13 patients were identified in whom either no intrinsic abnormality or poor runoff were evident after lysis and were treated with anticoagulation alone. CONCLUSIONS: These data show IATT to be especially suitable for thrombosis of native iliac or femoropopliteal arteries and infrainguinal vein grafts. IATT serves primarily as an adjunct in management of acute lower extremity ischemia. After successful IATT, subsequent therapy can be tailored to the anatomic cause of thrombosis. PMID- 8487358 TI - The effect of inguinal lymphatic manipulation on regional lymph flow patterns. AB - PURPOSE: Because of the proximity of the inguinal lymphatics and the femoral vessels, lymph vessel manipulation during inguinal dissection is unavoidable, and this project was undertaken to evaluate the consequences. METHODS: Thirty-five greyhound dogs underwent popliteal lymph node dissection, cannulation with microvascular silastic tubing, and infusion of 2.5% Patent blue violet (Sigma Chemical Co., St. Louis, Mo.) (visual enhancement) and technetium 99m-labeled human serum albumin (HSA). Animals underwent inguinal exploration with no manipulation (group 1; n = 9), local lymphatic ligation (group 2; n = 11), or radical excision and ligation (group 3; n = 15) of the inguinal lymph vessels. Lymphatic flow was calculated by 99mTc-HSA clearance (counts per minute) at the popliteal, inguinal, and iliac regions, before and after lymph vessel manipulation and was converted into percent change between the regions. RESULTS: There was statistically reduced intralymphatic radioactivity in groups 2 and 3 compared with group 1 (p < 0.001; Student t test), whereas there was no significant difference between groups 2 and 3. CONCLUSIONS: This demonstrates that lymphatic flow in this experimental model is significantly reduced when major channels are identified and ligated, although radical obliteration does not reduce flow more significantly than local ligation, implying that there is an alternate pathway for lymph flow. PMID- 8487359 TI - The influence of carotid siphon stenosis on short- and long-term outcome after carotid endarterectomy. AB - PURPOSE: This study was designed to determine whether the presence of ipsilateral carotid siphon stenosis influenced the risk of early and late stroke and death after carotid endarterectomy (CEA). METHODS: The outcomes of patients with moderate (20% to 49%), severe (> 50%), and no siphon stenosis were compared over a 16-year period from April 1976 to February 1992. Complete angiographic data were available in 393 carotid arteries. RESULTS: Siphon stenosis was found ipsilateral to the CEA in 84 (21.4%) of the arteries. Most lesions were in the 20% to 49% diameter-reducing range (77.4%), with the remainder in the greater than 50% range (22.6%). There were no occlusions. The perioperative mortality rate was nearly identical for the groups with and without siphon stenosis, 0.0% versus 0.6%, respectively (p = 0.99). Perioperative stroke morbidity rates (no stenosis, 2.3%; moderate stenosis, 3.1%; > 50% stenosis, 5.3%) were acceptable and were not statistically different (p > 0.38). Late ipsilateral stroke-free rates were similar in the groups with and without siphon stenosis. The 5- and 7 year stroke-free incidences were 88.5% and 83.4% versus 94.9% and 94.9%, respectively (p > 0.20) for the two groups. Long-term ipsilateral stroke-free rates were not significantly different in the subgroups with moderate (20% to 49%) and hemodynamically significant (> 50%) siphon stenosis. The 3- and 5-year ipsilateral stroke-free rates were 96.7% and 87.9% versus 94.6% and 94.6%, respectively (p = 0.69). Late death was more common in the group with siphon stenosis than it was in the group without siphon stenosis, 23.8% versus 12.5% (p = 0.02). Heart disease was responsible for most late deaths, 47% in both groups. Late stroke-related deaths were infrequent: 1.3% in patients with and 0.0% in patients without siphon stenosis. CONCLUSIONS: Although carotid siphon stenosis seemed to be associated with a higher risk of late death, it did not alter the short- and long-term stroke morbidity rates after carotid endarterectomy significantly. We conclude that the presence of carotid siphon stenosis should not influence the decision to perform carotid endarterectomy in patients with the appropriate indications. PMID- 8487360 TI - The importance of intraoperative detection of residual flow abnormalities after carotid artery endarterectomy. AB - PURPOSE: The efficacy of carotid endarterectomy in the prevention of strokes mandates low perioperative morbidity, as well as a low incidence of late ipsilateral stroke. This prospective study involving 430 patients (461 carotid endarterectomies) correlated the results of intraoperative assessment with end points of stroke and residual/recurrent internal carotid artery (ICA) stenosis. METHODS: Adequacy of the repair was assessed by ultrasound studies (duplex scan and pulsed Doppler spectral analysis) alone (n = 142), ultrasound studies and arteriography (n = 268), or clinical inspection (n = 51). After operation, duplex ultrasonography was used to confirm patency and categorize severity of ICA stenosis. At operation 26 carotid endarterectomy sites (5.6%), were revised based on intraoperative studies. RESULTS: Perioperative (30-day) morbidity rates were similar in patients with normal, mildly abnormal, or no ultrasound completion studies. There were six permanent (1.3%) and 12 temporary (2.6%) neurologic deficits and six deaths, including four fatal strokes and two fatal myocardial infarctions. By life-table analysis, the incidence of greater than 50% diameter reducing ICA stenosis or occlusion was increased (p < 0.007, log-rank test) in patients with residual flow abnormality or no study. More important, patients with normal intraoperative flow studies had a significantly lower rate of late ipsilateral stroke compared with the remaining patient cohort (p = 0.04, log-rank test). During the mean 30-month follow-up interval, the incidence of late stroke was increased (p = 0.00016) in patients with ICA restenosis or occlusion (3/35) compared with patients without recurrent stenosis (3/426). CONCLUSION: Confirmation of a normal repair at operation affords the best opportunity to minimize ischemic neurologic events and anatomic restenosis after carotid endarterectomy. PMID- 8487361 TI - Arteriovenous reversal for limb salvage in unreconstructible upper extremity arterial occlusive disease. AB - PURPOSE: Peripheral vascular disease of the upper extremity as a result of atherosclerotic disease or systemic vascular disorders presents a difficult management problem to the vascular surgeon. When extensive distal disease is present bypass procedures with standard arterial reconstruction techniques may not be possible. The use of retrograde perfusion to deliver oxygenated blood to the capillary bed by means of a normal venous system is not new. Flow reversal has been attempted in the myocardial, cerebral, and distal extremity circulations. Arteriovenous reversal (AVR) has been described for limb salvage in patients with upper extremity ischemia, with variable results. METHODS: We performed six AVR procedures on five patients with diffuse distal arterial disease and limb-threatening upper extremity ischemia. Two patients had insulin dependent diabetes, one had systemic lupus erythematosus (two extremities), one had rheumatoid arthritis with vasculitis, and the remaining patient had CRST (calcinosis, Raynaud's disease, sclerodactyly, telangiectasia) syndrome. The two patients with diabetes had systemic manifestations of atherosclerotic vascular disease and lower extremity ischemia; the remaining three patients had no evidence of atherosclerosis. In all patients the AVR was performed at the most distal site of nondiseased artery. RESULTS: Limb salvage was obtained in all cases; one patient had a healed minor digital amputation, and another patient had a healed major amputation. Clinical improvement with resolution of pain was achieved in five of six cases. The remaining patient had a significant diabetic neuropathy that was believed to contribute to her persistent pain. CONCLUSIONS: In patients with severe upper extremity ischemia not amenable to standard revascularization techniques, AVR should be considered to provide limb salvage and maximize hand function. PMID- 8487362 TI - Value of lower extremity venous duplex examination in the diagnosis of pulmonary embolism. AB - PURPOSE: This study tests the hypothesis that the absence of deep venous thrombosis (DVT) on lower extremity color-flow venous duplex examination (LECFD) combined with a non-high-probability ventilation/perfusion (V/Q) scanning results rules out pulmonary embolus (PE). The use of LECFD as a diagnostic aid for PE is based on data that show that 90% of PE originate from lower extremity DVT, and therefore on the assumption that PE cannot be present if DVT is not present as the source. METHODS: Over a 3-year period 51 patients with clinically suspected PE underwent LECFD and pulmonary angiography (PA) within 72 hours of each other. Forty-one patients also underwent V/Q scanning during the same time period. The results of LECFD and V/Q scans were compared with the results of PA, the gold standard for the diagnosis of pulmonary emboli. RESULTS: Results of LECFD were positive for DVT in seven of 16 cases of angiographically documented PE. Thus the "sensitivity" of LECFD as a diagnostic aid in cases of suspected PE is 44%. The results of LECFD and V/Q scans were combined and compared with the results of PA. A high-probability V/Q scanning result was considered positive for PE. Intermediate- and low-probability scanning results were considered negative, because in the literature the decision to begin heparin therapy is not made on the basis of this result. The combination of test results was considered positive if either test result was positive and negative only if results of both were negative. With these criteria the combination of test results was positive in only 62% of cases of angiographically documented PE. CONCLUSIONS: If treatment of suspected PE were based on LECFD alone or on duplex combined with V/Q scanning, 40% to 50% of patients with PE would remain untreated. In cases of suspected PE where these noninvasive tests do not confirm its presence, PA should be performed. PMID- 8487363 TI - Surgical management of aortic aneurysm and coexistent horseshoe kidney: review of a 31-year experience. AB - PURPOSE: The coexistence of horseshoe kidney and aortic aneurysm poses a technical challenge to the vascular surgeon at the time of aneurysm repair. Clinical experience with this problem was reviewed to assess the results of treatment and to develop guidelines for the treatment of patients with horseshoe kidney and aortic aneurysm. METHODS: From 1960 through 1991, 19 patients with associated horseshoe kidney (HSK) required repair of abdominal aortic aneurysm at the Cleveland Clinic. Seventeen men and two women, with a mean age of 67 years, underwent 16 elective and three urgent operations. The HSK was found before operation in 16 patients (84%), whereas the remaining three were discovered at operation. Computed tomography and intravenous pyelography were the most reliable means of preoperative diagnosis, whereas ultrasonography and aortography were less dependable. Mean size of abdominal aortic aneurysm was 6.1 cm. The mean preoperative creatinine level was 1.5 mg/dl. The surgical approach was transperitoneal in 16 patients and retroperitoneal in three. Division of the renal isthmus was avoided in all patients. RESULTS: Renal artery anomalies were encountered in 14 patients (74%). Renal arterial continuity was established by a variety of techniques, including branch grafts or reimplantation into the aortic graft. Abnormal preoperative renal function was associated with a significantly increased risk for early postoperative hemodialysis (p = 0.02). There were three postoperative deaths, and the mortality rate for patients who required dialysis (67%) was significantly higher (p = 0.05) than that for patients who did not (6.3%). There were six late deaths at a mean follow-up interval of 57 months. CONCLUSIONS: The most important aspect of HSK, therefore, is the appropriate surgical management of frequent renal artery anomalies. We currently believe this is best achieved with retroperitoneal exposure. PMID- 8487364 TI - Preservation of renal function in juxtarenal and suprarenal abdominal aortic aneurysm repair. AB - PURPOSE: Deterioration in renal function is a common cause of morbidity in patients treated surgically for juxtarenal and suprarenal abdominal aortic aneurysms. We reviewed our experience over the last 8 years with 65 consecutive patients undergoing juxtarenal (n = 31) or suprarenal (n = 34) abdominal aortic aneurysm repair. METHODS: The aneurysms were repaired with a transabdominal (n = 8), thoracoabdominal (n = 4), retroperitoneal (n = 22), or thoracoretroperitoneal (n = 31) approach. Proximal aortic clamps were placed at the suprarenal, supra superior mesenteric artery, or supraceliac level. Renal hypothermia with cold heparinized saline solution renal artery perfusion was used to protect renal function in 38 patients with either preoperative renal insufficiency or with anticipated prolonged renal ischemia (> 30 minutes). Concomitant renal artery reconstruction was required in 30 patients. RESULTS: Significant operative morbidity developed in 23 (35.3%) patients. There was one (1.53%) perioperative death (0 to 90 days). Temporary dialysis was necessary in two patients. Preoperative renal insufficiency was a significant risk factor on multivariate analysis for a decline in renal function during the first postoperative week. However, serum creatinine concentration had returned to baseline or improved in all patients but two (3.1%) at the time of discharge. In spite of significantly longer renal ischemia, discharge creatinine levels were, on univariate analysis, statistically less than baseline creatinine levels in patients with suprarenal aneurysms, patients requiring renal reconstruction, and patients treated with renal hypothermia. The location of the proximal aortic clamp was not a factor in postoperative morbidity. There was no significant difference between juxtarenal and suprarenal aneurysms with respect to operating room time, transfusion requirements, days intubated, resumption of oral diet, or the length of hospitalization. CONCLUSIONS: Careful consideration of the route of exposure, location of the proximal aortic clamp, and the preservation of renal function with renal hypothermia and with the repair of significant renal artery lesions will result in minimal morbidity and mortality in patients requiring surgery for juxtarenal or suprarenal abdominal aortic aneurysms. PMID- 8487365 TI - Angiographic follow-up after laser-assisted balloon angioplasty. AB - PURPOSE: The purpose of this study was to obtain angiographic documentation of patency and recurrence rates after laser-assisted balloon angioplasty. METHODS: A prospective assessment of laser-assisted balloon angioplasty (LABA) was performed in 35 limbs of 33 patients with femoral popliteal atherosclerotic disease. There were 21 male and 12 female patients with a mean age of 60.6 years. Indications were intermittent claudication in 19, rest pain in nine, and ischemic ulcer/gangrene in seven limbs. There were 23 totally occluded (mean length 6 +/- 3.8 cm) and 12 stenotic arteries. LABA was achieved with a pulsed Nd:YAG laser with 10 to 25 W and a 2.2/3 mm sapphire probe, followed by balloon dilatation in all but four limbs. RESULTS: Immediate technical success (< or = 50% residual stenosis) was achieved in 27 (77%) of 35 limbs. Mean ankle/brachial index improved from 0.49 to 0.80 (p < 0.05). Major complications included three perforations, three dissections, and two emboli. Two additional limbs required operation at less than 30 days for a 30-day patency rate of 71.4%. Long-term clinical and noninvasive follow-up ranged from 1 to 55 months (mean 17.68 months). Twenty-nine angiograms were obtained from 3 to 49 months after LABA. Nineteen limbs underwent at least one angiogram, seven underwent two, and three limbs underwent three angiograms. Eleven of the 19 limbs showed evidence of restenosis greater than 50%, all within 12 months. The cumulative patency rate was 71.5% at 1 month, 39.7% at 6 months, and 31.3% at 12, 24, and 36 months. CONCLUSIONS: LABA with the Nd:YAG laser has a 30-day success rate of 71.4%. Angiographic follow-up demonstrates a high incidence of restenosis (> 50%), usually within 12 months. Approximately 50% of limbs eventually required reintervention within 1 year. In view of the disappointing early results, the use of LABA must remain strictly investigational. PMID- 8487366 TI - Training of vascular surgeons: the two-class system. PMID- 8487367 TI - The Residency Review Committee for Surgery and the training of vascular surgeons. AB - PURPOSE: This article reviews the activities and actions of the Residency Review Committee (RRC) for Surgery in the accreditation process of of vascular surgery training programs since 1983. METHODS: The substantial changes of the Special Requirements for Graduate Education in General Vascular Surgery are discussed for 1983, 1987, 1989, and 1992. The rank-ordered list of RRC citations is reviewed. The national resident operative statistics for the past 4 years are reported for both general and vascular surgery residents. RESULTS: Changes in the Special Requirements have included deletion of two of the four types of programs, elimination of the need for institutional programs in specialties other than core general or thoracic surgery, and relaxation of the restriction against concurrent resident assignment. The most common citation continues to be the negative impact on general surgery residents. Nevertheless national operative statistics show a favorable increase in case load for both general and vascular surgery residents. CONCLUSIONS: Future challenges to surgical education and practice are summarized; the solutions to these challenges will require cooperative efforts of the RRC, the American Board of Surgery, and a number of specialty societies and credentialing or regulatory bodies. PMID- 8487368 TI - Class and conflict in vascular surgery. PMID- 8487369 TI - Differentiation of two rabies strains in Estonia with reference to recent Finnish isolates. AB - We compared 24 rabies samples collected in Estonia in 1989 to 1992, to identify the kinds of rabies strains circulating in this country. Eleven of the strains came from the islands of Saaremaa, Hiiumaa and Muhu, off the Baltic coast; 13 came from the mainland. The mainland strains, like those from the 1988 to 1989 epizootic in Finland, were antigenically different from the 11 island isolates. The island isolates reacted negatively with monoclonal antibody W-187.5 as does the SAD B19 rabies vaccine strain, currently spread as baits to wildlife in Finland and other parts of Europe. In order to unambiguously distinguish the island isolates from the SAD B19 vaccine, we developed a polymerase chain reaction (PCR) protocol for rabies, followed by a single restriction enzyme digestion. This method enabled the island isolates to be differentiated with ease from the vaccine strain SAD B19 at the level of the nucleoprotein-coding region. Additionally, this method had the ability to distinguish other polar field isolates examined, as well as the laboratory challenge virus strain CVS, from SAD B19 vaccine. Modifications of the above PCR method may be used for epidemiological investigations of new outbreaks or of outbreaks involving different species. PMID- 8487370 TI - Experimental Borrelia burgdorferi infections in the white-footed mouse, deer mouse, and fulvous harvest mouse detected by needle aspiration of spirochetes. AB - Three methods were tested for recovering Borrelia burgdorferi from live mice onto BSK II culture medium. Four laboratory-reared Peromyscus leucopus were inoculated intraperitoneally with the JD-1 isolate of Borrelia burgdorferi. Borrelia burgdorferi spirochetes were recovered from 13 of 20 (65%) samples taken by needle aspiration between days 7 and 40 post-inoculation (PI) and from 1 of 16 samples of skin obtained by ear punch biopsy during the same sampling period. Spirochetes were not recovered from culture media inoculated with mouse blood. The use of needle aspirates for recovering spirochetes was compared among three species of mice: P. leucopus, P. maniculatus, and Reithrodontomys fulvescens. Spirochetes were isolated from 14 of 15 aspiration samples from four P. maniculatus, 12 of 20 from three P. leucopus, and 15 of 20 from four R. fulvescens taken between days 7 and 48 PI. Spirochetes were isolated from only one aspiration sample between days 80 and 95 PI from any of the mice tested. Needle aspiration was an efficient method for repeated recovery of B. burgdorferi from live, experimentally infected mice. We also document R. fulvescens as an experimental host for B. burgdorferi. Based on their susceptibility to infection, all species of mice tested herein may play a role in the epidemiology of Lyme disease where their distribution is compatible with endemic transmission. PMID- 8487371 TI - A serologic survey for viruses and Mycoplasma pulmonis among wild house mice (Mus domesticus) in southeastern Australia. AB - Plasma samples from 267 wild house mice (Mus domesticus) trapped at 14 sites in southeastern Australia were screened for antibody to 14 viruses normally associated with laboratory-reared rodents and to Mycoplasma pulmonis. Serologic prevalence was high for murine cytomegalovirus (99%, n = 94), murine coronavirus (95%), and murine rotavirus (74%). Samples from mice collected at all sites contained antibody to these viruses. The serologic prevalence was lower for mouse adenovirus, strain K87 (37%), parvovirus (33%), and reovirus type 3 (28%), with substantial site-to-site variation. Plasma from mice collected at 12 sites contained mouse adenovirus or reovirus antibody, and samples from mice at eight sites contained parvovirus antibody. Parvovirus-antibody positive mice were typically from high density populations or from low density populations that had recently declined from high density. Antibody to lymphocytic choriomeningitis virus (LCMV) and Sendai virus occurred at only three sites, and the serologic prevalence was very low (9.6% and 1.8%, respectively). All of the LCMV-positive mice were from northeastern New South Wales. The presence of this zoonotic virus in a mouse plague-prone region raises questions about human health risks resulting from cohabitation with large numbers of mice. It appeared that mouse populations at high density or declining from high density had higher prevalence of viral antibody than populations that had been at low or moderate density for some time. Thus, viral epizootics may occur among high-density populations and may be responsible for or precipitate declines in mouse density. These data raise the possibility of rodent viruses having potential as biological control agents. PMID- 8487372 TI - Serologic survey for antibodies to Borrelia burgdorferi in white-tailed deer in Georgia. AB - A serologic survey for antibodies to Borrelia burgdorferi utilizing an enzyme linked immunosorbent assay (ELISA) was conducted on white-tailed deer (Odocoileus virginianus) serum samples collected in Georgia (USA) from 1979 to 1990. Serologic results from four regions (Barrier Islands, Coastal Plain, Piedmont, and Mountain) and three age classes (0.5, 1.5, and > or = 2.5 yr) were compared. Antibody prevalence, as determined by positive results at a 1:64 dilution or higher, was 36% in the Barrier Islands, 14% in the Coastal Plain, 8% in the Piedmont, and 4% in the Mountain regions. Statewide antibody prevalence was 19%. Antibody titers generally were low, and if a more conservative cutoff titer of 1:128 were used, the statewide prevalence estimate would have been reduced to 5%. Antibody prevalence as determined at this higher cutoff value, however, still remained highest in the Barrier Islands and lowest in the Mountains. Prevalence estimates were lower in the 0.5-yr age class than in the 1.5-yr or > or = 2.5-yr age class (P < 0.05). A more in-depth retrospective study of the Barrier Islands region from 1971 to 1985 revealed a 50% overall antibody prevalence; positive results were found in every year represented except 1990. Based on these results, we propose that B. burgdorferi has been present in Georgia since at least 1971. PMID- 8487373 TI - The epizootiology of eustrongylidosis in wading birds (Ciconiiformes) in Florida. AB - A total of 2,167 individuals representing 15 species of wading birds was examined for infection with the nematode Eustrongylides ignotus in Florida (USA). Ten of the species were infected with the greatest prevalences occurring in great blue herons (Ardea herodius) (33%), great egrets (Casmerodius albus) (22%), and snowy egrets (Egretta thula) (19%). Among nestlings, prevalences increased with age. This parasite was estimated to cause at least 80% mortality among nestling ciconiiforms at one colony in Everglades National Park, and was found in 15% of nestling ardeids throughout the state. Despite wide sampling efforts, infected fish (second intermediate hosts) were only found at six sites in Florida, all of which had been physically altered, such as with canals and ditches, and had an anthropogenic (human-caused) source of nutrient pollution. Colonies near sources of infected fish experienced significantly higher prevalences of eustrongylidosis that did colonies for which no source of infected fish could be found within 20 km. Higher prevalences were found at freshwater and estuarine mainland colonies than at marine colonies. Densities of aquatic oligochaetes, which may act as first intermediate hosts, were highest at sites containing infected fish and at sites with a source of nutrient pollution. Conservation and management of wading bird species should include consideration of this disease, epizootics of which seem to be linked to nutrient pollution. PMID- 8487374 TI - Pathogenesis of Eustrongylides ignotus (Nematoda: Dioctophymatoidea) in Ciconiiformes. AB - Natural (n = 157) and experimental (n = 5) infections with the nematode Eustrongylides ignotus are described for ciconiforms collected in Florida (USA). Larvae perforated the ventriculus in 3 to 5 hr and caused hemorrhage and bacterial peritonitis that sometimes progressed to a fibrous peritonitis with extensive adhesions. Severity of the disease was related inversely to the age of the bird and directly to the number of parasites involved. Some infections in adult birds were resolved. As a consequence of eustrongylidosis, anorexia and behavioral abnormalities resulted in emaciation and may have predisposed birds to traumatic death. Host-parasite adaptations apparently were not adequate for nestling ciconiforms as death of nestlings usually occurred before infections become patent (longer than 14 days, less than 23 days). Patent infections were found in both color morphs of the great blue heron (Ardea herodius), and in great egrets (Casmerodius albus) and snowy egrets (Egretta thula). We propose that birds of the family Ardeidae are the primary definitive hosts. PMID- 8487375 TI - Evidence for arrested development of abomasal nematodes in white-tailed deer. AB - White-tailed deer (Odocoileus virginianus) obtained from Noxubee National Wildlife Refuge, Noxubee County, Mississippi (USA) during April (n = 3), June (n = 5), September (n = 5), and November (n = 5) 1989, were necropsied for counting and identification of adult and larval stages of abomasal nematodes. Fourth-stage larvae (L4) (n < or = 25) from each deer were randomly selected for measurement of total worm length and width. Adults of four worm species were found: Mazamastrongylus odocoilei, M. pursglovei, Ostertagia mossi, and O. dikmansi. There were no differences between months in adult male worm burdens for all species except O. dikmansi for which the April worm burden was greatest (P < or = 0.05). Overall, the length of L4 ranged from 929 to 4,361 microns. There were no significant differences (P > 0.05) between months in the mean length (1,334 to 1,532 microns) of L4. Except for low numbers of developing fourth-stage larvae (length > 1,650 microns) in April (2.6%), June (7.4%), September (11.3%), and November (3.7%), worms were early fourth-stage larvae (EL4) or fully developed adults. Overall, the proportion of EL4 in individual deer ranged from 19 to 97%; in male (n = 3) and female (n = 15) deer the proportions of EL4 were 22.5% and 67%, respectively. The mean proportions of EL4 in female deer were 51.4% (April), 63.2% (June), 78.1% (September), and 74.7% (November), but there was no difference (P > 0.05) among the 4 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487376 TI - Factors affecting Parelaphostrongylus tenuis in white-tailed deer (Odocoileus virginianus) from Maine. AB - White-tailed deer (Odocoileus virginianus) collected in Maine (USA) from November 1988 to December 1989 were examined for Parelaphostrongylus tenuis. Relationships of deer age class, sex, collection year, and deer density to prevalence and intensity of P. tenuis infections were analyzed. Prevalence increased with deer age (P < 0.001) and interaction of deer age class and collection year (P < 0.001). Prevalence did not vary by year in deer > or = 1 yr old (85%, n = 519), but was higher in fawns in 1988 (66%, n = 87) than 1989 (23%, n = 73, P < 0.001). Based on such yearly variations, prevalence in fawns during late autumn could provide an index of annual transmission of P. tenuis. Intensity of P. tenuis averaged 2.5 worms per infected fawn (SD = 2.8, n = 72) versus 3.9 (SD = 3.1, n = 375) in deer > or = 1 yr old (P = 0.032). Neither prevalence (P > 0.50) nor intensity (P > 0.50) of infection was associated with deer density over a range of 1.4 to 5.8 deer per km2. Heads and fecal samples from the same individuals (n = 42) provided prevalence estimates of 73% and 44%, respectively. No differences in prevalence, intensity, or geographic distribution of P. tenuis in adult deer collected in Maine during fall were evident between the late 1980's (this study) and the late 1960's (Gilbert, 1973).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487377 TI - Pneumocystis carinii and helminth parasitism in shrews Sorex araneus and Sorex caecutiens. AB - The prevalence of Pneumocystis carinii was compared in two species of shrews, Sorex araneus and Sorex caecutiens in Finnish Lapland. The overall prevalence of P. carinii in S. araneus was 70% and in S. caecutiens was 17%. The prevalence for S. araneus is the highest reported for wild animals. The interspecific differences in prevalence were significant for all sex and age groups except for adult males. Based on multiway contingency tables (log-linear models), there was no dependence between sex or age of S. araneus and occurrence of P. carinii. In individual S. araneus the intensity of P. carinii was not related to the total number of helminths or the number of helminth species, and no dependence was observed between the presence of P. carinii and various helminth species. PMID- 8487378 TI - Infestation of northern spotted owls by hippoboscid (Diptera) flies in northwestern California. AB - Hippoboscid flies were found on 62 (17%) of 382 northern spotted owls (Strix occidentalis caurina) captured between April and September, 1986 through 1990. Two species of hippoboscids were identified: Icosta americana and Ornithomya anchineuria. Male and female adult spotted owls had similar prevalences and relative densities of hippoboscid flies. Juvenile owls had lower prevalence and relative densities than adults. There were no significant differences in mean intensity of hippoboscids on adult male, adult female and juvenile spotted owls. Relative densities of flies infesting adult owls were significantly greater during years of increased fall temperatures, decreased winter precipitation, and decreased summer temperatures. PMID- 8487379 TI - Counting dead birds: examination of methods. AB - We studied three methods (line transect, circular quadrat, complete count) for estimating density of dead birds, using models of sparrows and meadowlarks placed at a density of 50 birds of each type/ha. Line transects with a 500-m search line were used in cultivated pasture and native prairie habitats. The number of birds found by individual searchers in line transects varied markedly, particularly, in pasture habitat. More birds were found, and birds were detected at a greater distance, in prairie than in pasture. More meadowlarks than sparrows were found in both habitats but the mean estimated density of meadowlarks was greater than that of sparrows only in prairie. The number of birds found during most searches was less than that suggested for estimating density accurately and longer search lines were required. Density estimates obtained using circular plots to sample 10% of the prairie area ranged from 20 to 80 birds/ha for meadowlarks and from 10 to 60 birds/ha for sparrows in prairie habitat. A complete search by 25 volunteers spaced at 4 m intervals detected 90% of meadowlarks but only 62% of sparrows in pasture habitat. Mean (SD) time for a single search, including searchers and recorders, was 3.0 (0.8), 1.5 (0.3), and 7.5 person-hours, for line transect, circular plot and complete search, respectively. PMID- 8487380 TI - Evaluation of baits for oral rabies vaccination of mongooses: pilot field trials in Antigua, West Indies. AB - A field study was conducted on the island of Antigua, West Indies, to evaluate baits for delivering an oral rabies vaccine to the small Indian mongoose (Herpestes auropunctatus). Tracking tiles were used to determine that mongooses were nonselective and took both egg-flavored polyurethane baits and fish-flavored polymer baits containing several different food materials. A high proportion of baits were taken the day of placement with minimal disturbance by nontarget species. DuPont Oil Blue A dye was an effective short-term biomarker for use in baits; based on its subsequent detection in mongooses, some of the population had consumed and not cached or discarded baits. Central point baiting stations showed promise as an alternative delivery technique. PMID- 8487381 TI - Serum enzymes as indicators of capture myopathy in mallards (Anas platyrhynchos). AB - Serum concentrations of the enzymes creatine kinase (CK) and aspartate aminotransferase (AST) were measured in captive and wild mallards (Anas platyrhynchos) as indicators of muscle damage. Baseline values for both enzymes were determined from six captive male mallards. During winter 1990 to 1991, six diets (including controls) representative of food available in the Mississippi alluvial valley were fed to captive female mallards housed in an outdoor aviary at the White River National Wildlife Refuge, Arkansas County, Arkansas (USA). Controlled handling of penned mallards resulted in elevated serum CK (means = 1,352 IU/liter; SD = 1,212) and AST (means = 101 IU/liter; SD = 95) concentrations consistent with myopathies. These serum enzyme elevations were not affected (P > 0.3) by dietary selenium concentrations in the six diets or by energy malnutrition suffered by birds fed soybeans. Capture of wild mallards with an entanglement type rocket net resulted in serum CK and AST concentrations (means = 12,035 and 330 IU/liter; SD = 8,125 and 171, respectively) that were higher (P < 0.001) than those reported after capture with an enveloping type rocket net. Baseline values, controlled handling values, and entanglement rocket net values for serum CK and AST all differed (P < 0.0001). PMID- 8487382 TI - Evaluation of the Bionic trap to quickly kill fisher (Martes pennanti) in simulated natural environments. AB - The Bionic trap equipped with a 10 cm aperture bait cone and cocked to eight notches quickly killed nine of nine fishers (Martes pennanti) in simulated natural conditions. Mean (+/- SE) estimated times to loss of consciousness and heartbeat were < or = 55 sec and 305 (+/- 8) sec, respectively after firing the trap. This study confirmed that the Bionic trap can be expected to render > or = 70% of captured fishers irreversibly unconscious in < or = 3 min (P < 0.05). PMID- 8487383 TI - Evaluation of mechanically improved Conibear 220 traps to quickly kill fisher (Martes pennanti) in simulated natural environments. AB - Mechanically improved Conibear 220 traps failed to render irreversibly unconscious in < or = 3 min fishers single-struck in the head-neck region, or double-struck in the neck and thorax regions. Although the Conibear 220 trap is often recommended as an alternative to the steel leghold trap, it is unlikely that it has the potential to humanely kill fisher. PMID- 8487384 TI - Assessment of the Kania trap to humanely kill red squirrels (Tamiasciurus hudsonicus) in enclosures. AB - The Kania trap equipped with side wings and baited with a pine cone quickly killed nine of nine red squirrels (Tamiasciurus hudsonicus) in enclosures. Mean times to loss of consciousness and heartbeat were estimated at < or = 65 sec and < or = 91 sec, respectively, after firing the trap. Thus the Kania can be expected to render > or = 70% of captured red squirrels irreversibly unconscious in < or = 3 min (P < 0.05). PMID- 8487385 TI - An epizootic of Edwardsiella tarda in largemouth bass (Micropterus salmoides). AB - Edwardsiella tarda, an opportunistic bacterial pathogen, was isolated from dying largemouth bass (Micropterus salmoides) during an epizootic in a eutrophic lake system, Lochloosa Lake, Florida, USA. Approximately 1,500 adult fish died over a 6-wk period during the late summer and early fall of 1991. A mixed population of aerobic bacteria (E. tarda, Aeromonas hydrophila, and Pseudomonas sp.) was isolated from deep cutaneous ulcers and intestines of moribund bass. However, E. tarda in pure culture was the only bacterium isolated from several viscera of several fish; E. tarda may be the etiologic agent responsible for some episodes of seasonal mortality in largemouth bass. PMID- 8487386 TI - The prevalence of Trichinella sp. in Arctic foxes (Alopex lagopus) in Svalbard. AB - The prevalence of Trichinella sp. in arctic foxes (Alopex lagopus) from Svalbard was studied from 1983 to 1989. Diaphragms of 697 foxes were examined for larvae; 59 foxes (8.5%) were infected. The prevalence of Trichinella sp. increased from 4% in juveniles to 36% in foxes aged more than 6 years of age. There were no significant correlations when condition and body weight each were correlated to the occurrence and number of larvae of Trichinella sp. More foxes were infected in the northern than in the central part of Svalbard. There were only minor differences in prevalence among years. PMID- 8487387 TI - Prevalence of Encephalitozoon cuniculi antibodies in terrestrial mammals in Iceland, 1986 to 1989. AB - Antibodies to Encephalitozoon cuniculi were found in wild arctic foxes (Alopex lagopus), feral mink (Mustela vison), wood mice (Apodemus sylvaticus) and house mice (Mus musculus) in Iceland. Animals with antibodies were found throughout the country. No lesions attributable to encephalitozoonosis were found in adult animals necropsied. However, one arctic fox cub with a neurological disorder had pathological and serological evidence of encephalitozoonosis. PMID- 8487388 TI - A fibrosarcoma in the skeletal muscle of a capybara (Hydrochoerus hydrochaeris). AB - An 8-yr-old male capybara (Hydrochoerus hydrochaeris), a resident of an urban zoological collection in upstate New York (USA), had a mass posteroventral to its left stifle; it was of unknown duration. The mass was a fibrosarcoma based on invasive sheets of interwoven spindle-shaped neoplastic cells with moderate associated extracellular matrix composed of collagen fibers. Supportive immunohistochemical staining was positive for vimentin but negative for cytokeratins, desmin, and myoglobin. The animal subsequently died of unknown causes. This is the first known report of a neoplasm in a capybara. PMID- 8487389 TI - A survey of lead poisoning in wild waterfowl in Japan. AB - Ingested shotgun pellets were found in 13 of 56 hunter-killed wild waterfowl between October and December 1991 from two hunting grounds in Japan. Four of 33 other waterfowl found dead in lightly hunted areas between January 1991 and March 1992 were diagnosed as having lead poisoning. We propose that lead poisoning maybe a threat to waterfowl in Japan. PMID- 8487390 TI - Differences in blood haptoglobin and length-mass relationships in river otters (Lutra canadensis) from oiled and nonoiled areas of Prince William Sound, Alaska. AB - Significant differences in levels of blood haptoglobin occurred between river otters (Lutra canadensis) inhabiting oiled (mean = 361 mg/100 ml, SD = 38, n = 6) and nonoiled (mean = 306 mg/100 ml, SD = 87, n = 8) areas of Prince William Sound, Alaska (USA) following the Exxon Valdez oil spill in 1989. Additionally, male river otters from oiled areas had significantly lower body mass (1.13 kg) than male otters from nonoiled areas. We propose oil-related causes for these differences. PMID- 8487391 TI - Physical and behavioral findings in a pseudohermaphrodite American bison. AB - A pseudohermaphrodite American bison (Bison bison) behaved like an adult male when interacting with adult females, but like an adult female when interacting with adult males. Its chromosomes were a normal 60, XX and it had a uterus; but it had bilateral testes rather than ovaries. Skull measurements were intermediate between a bull and a cow. Gonadotrophin levels were typical of ovariectomized domestic cows or steers. PMID- 8487392 TI - Hiatal hernia in a harbor porpoise (Phocoena phocoena). AB - We observed the displacement of the first compartment of the stomach through the diaphragmatic hiatus into the thoracic cavity in an immature harbor porpoise (Phocoena phocoena). This hiatal hernia, coupled with a severe pneumonia, contributed to the emaciation and death of the animal. PMID- 8487393 TI - Notes on the first known avian cholera epizootic in wildfowl in North America. PMID- 8487394 TI - US-based world medical relief group finds charity begins at home. PMID- 8487395 TI - What can Tillery tell Hillary? Tiny town reforms its own health care. PMID- 8487396 TI - Spouses of the chronically ill help each other cope. PMID- 8487397 TI - 'Health of nation at stake' says Elders. PMID- 8487398 TI - From the Food and Drug Administration. PMID- 8487399 TI - From the Centers for Disease Control and Prevention. Impact of the expanded AIDS surveillance case definition on AIDS case reporting--United States, first quarter, 1993. PMID- 8487400 TI - From the Centers for Disease Control and Prevention. Populations at risk from air pollution--United States, 1991. PMID- 8487401 TI - The biggest roadblock to reform--this Congress is independent of Clinton. PMID- 8487402 TI - Health insurance reform and the physician-patient relationship. PMID- 8487403 TI - Health insurance reform and the physician-patient relationship. PMID- 8487404 TI - Medical care is not health care. PMID- 8487405 TI - Incorporating prevention in managed care. PMID- 8487407 TI - Trauma surgeons: primary care practitioners by default. PMID- 8487406 TI - Rehabilitating the medical specialist. PMID- 8487408 TI - Uninsured children and national health care reform. PMID- 8487409 TI - Health care access and birth outcome. PMID- 8487410 TI - Health care access and birth outcome. PMID- 8487411 TI - Prisoners' access to medications. PMID- 8487412 TI - 'Cat': methcathinone--a new drug of abuse. PMID- 8487413 TI - The foreskin. PMID- 8487414 TI - Effects of lower surgical fees on the use of physician services under Medicare. AB - BACKGROUND AND OBJECTIVE: The changes in physician fees that will occur under the resource-based Medicare Fee Schedule (MFS) are similar to those that took place under the Omnibus Budget Reconciliation Act of 1987 (OBRA 87), when Medicare fees for selected "overpriced" procedures and diagnostic tests were reduced. To gain insight regarding the changes in utilization that may occur under the MFS, this study examines the effects of the OBRA 87 fee reductions on the use of physician services by Medicare patients. DATA AND METHODS: The five specialties that were most affected by the OBRA 87 fee reductions were studied: ophthalmology, thoracic surgery, urology, orthopedic surgery, and gastroenterology. Medicare physician claims files for 1987 and 1989 were used to obtain data on utilization and fees. Multivariate regression analysis was used to assess the effect of changes in fees on changes in utilization. RESULTS: The best estimate of the effect of the OBRA 87 fee reductions on overall physician-services utilization, obtained by pooling the five study specialties, was that every 1% decrease in fees led to a 0.09% decrease in the volume and complexity of services (95% confidence interval, 0.49% decrease to 0.31% increase). This result was not sensitive to minor changes in the covariates included in the regression model. CONCLUSION: To calculate payment levels during the transition to the MFS, the Health Care Financing Administration assumed that physicians whose Medicare revenue declines under the MFS will increase service volume and complexity enough to make up one half of the lost revenue. The findings of this study suggest that the Health Care Financing Administration's assumption was, at best, extreme. PMID- 8487415 TI - Medical students' attitudes toward providing care for the underserved. Are we training socially responsible physicians? AB - OBJECTIVE: To investigate the association between attitudes toward caring for the medically indigent and years of medical training. DESIGN: Questionnaire comparing attitudes of first-year medical students (MS-Is) and fourth-year medical students (MS-IVs). SETTING: Southwest medical school. PARTICIPANTS: A total of 83 (67%) male and 41 (33%) female MS-I and 65 (73%) male and 24 (27%) female MS-IV volunteers. MAIN OUTCOME MEASURE: Self-report, attitudinal scale developed for this study that provided a measure of overall attitudes, perceived societal expectations, physician/student responsibility, personal efficacy, and provision of basic services and expensive procedures. RESULTS: Overall attitudes were significantly less favorable for MS-IVs (95% confidence interval [CI], 99.6 to 106.2) than MS-Is (95% CI, 109.5 to 114.3, P < .0001). Except for basic services (P = .46), MS-IVs had worse attitudes on all attitudes subscales. Male MS-IVs reported significantly less favorable attitudes than male MS-Is in the areas of general attitudes (P = .03) and physician/student responsibility (P = .01). Female medical students showed no significant differences across classes (P > .05). Except for physician/student responsibility, female medical students' attitudes were more favorable than those of males, regardless of class. CONCLUSIONS: The MS-IVs are less favorably inclined toward caring for the medically indigent than MS-Is, though these differences are apparent only for males. Further research is needed to explore why females appear to be more resistant to attitude changes, and what educational interventions are necessary to better train physicians to respond to national health care issues. PMID- 8487416 TI - Managed competition that works. AB - President Clinton has advocated managed competition within a global budget as a long-term strategy for simultaneously controlling health care costs and expanding access to medical care to all Americans. This proposal is intended to show how these two seemingly conflicting goals can be simultaneously accomplished. Managed competition, as it has been conceptualized to date, is primarily a strategy for reforming the system of providing health services. To work, it must be joined with a strategy for reforming our system of financing and paying for those services and of limiting overall system capacity. "Managed Competition That Works" is a proposal that would create a single trust-funded national system of health insurance, implemented through a system of vouchers to individuals. Global budgeting would be accomplished through establishment of the voucher's value each year. The trust fund would pay health plans for all medical care by capitation, but health plans would be free to negotiate a variety of payment arrangements with physicians, hospitals, and other providers. All plans would be required to offer a standard package of benefits, but would have great flexibility in offering benefits beyond the scope of the standard package, if those benefits replace high-cost with lower-cost services or permit the plan to compete more effectively for market share. This proposal would establish firm but acceptable national budget limits; provide universal, comprehensive, and uniform insurance coverage; eliminate cost shifting; encourage competition; reward efficiency improving innovation; greatly reduce the need for centralized micromanagement of medical care; and retain local determination and a somewhat reduced level of consumer choice. Although this proposal is written as a national plan, trust funds could be implemented at the state level, if problems associated with portability of benefits among states could be solved. PMID- 8487417 TI - What's wrong with the ERISA vacuum? Employers' freedom to limit health care coverage provided by risk retention plans. PMID- 8487418 TI - Caring for the poor. Council on Ethical and Judicial Affairs, American Medical Association. PMID- 8487419 TI - Hawaii's employer mandate and its contribution to universal access. AB - Much national debate centers around national models in which an employer mandate plays an important role in providing for health care coverage for all Americans. Hawaii has had the nation's only health insurance employer mandate for almost 20 years, yet little is known nationally about the mandate itself or Hawaii's experience with it. This article describes the long-term effects of Hawaii's employer mandate on health care access and costs, and offers reflections on the potentials of national health care reform based on Hawaii's experience. PMID- 8487420 TI - Community-oriented primary care. The cornerstone of health care reform. AB - The current high-cost health care delivery system, which places greater emphasis on acute hospital care than on community-based primary and preventive care, is no longer viewed by policymakers, politicians, and the American public as the ideal model for organizing and providing health care services. Americans want change; however, politicians are responding with a barrage of disjointed finance and cost containment proposals that fail to address the organization and provision of health care services. Nevertheless, to adequately address problems of cost, access, and quality, reform proposals will need to consider delivery models that create a balance between medical care and health care, between public health and personal health services, and between curative and preventive care. The community oriented primary care model and the discipline of community and socially responsive medicine is a process for making a health care system more rational, accountable, appropriate, and socially relevant to the public. Consequently, this model, which is now at a pivotal point in its evolution, may serve as a paradigm for reforming the organization and provision of health care services in America. PMID- 8487421 TI - Using academic health centers to help avoid health care's next crisis. PMID- 8487422 TI - Physician response to fee changes. A contrary view. PMID- 8487423 TI - Grading President Clinton's health proposal. PMID- 8487424 TI - American health care system management objectives. The aura of inevitability becomes incarnate. PMID- 8487425 TI - Attempting to reduce hospital costs by strengthening primary care institutions. The Dutch Health Care Demonstration Project in the new town of Almere. PMID- 8487426 TI - Bridging the gap between expert and public views on health care reform. PMID- 8487427 TI - A piece of my mind. The bottom line. PMID- 8487428 TI - A piece of my mind. Cognocardiology. PMID- 8487429 TI - Imaging methods for sinusitis. PMID- 8487430 TI - Prophylactic mastectomy for familial breast cancer. PMID- 8487431 TI - Stool analysis for asthma. PMID- 8487432 TI - Gay, lesbian physicians meet, march, tell Shalala bigotry is health hazard. PMID- 8487433 TI - 'Window to tobacco-free world' clouded slightly. PMID- 8487434 TI - Childhood immunization initiative goes forward. PMID- 8487435 TI - Varied mammogram readings worry researchers. PMID- 8487436 TI - From the National Institutes of Health. PMID- 8487437 TI - From the Centers for Disease Control and Prevention. Update: investigations of persons treated by HIV-infected health-care workers--United States. PMID- 8487438 TI - Cardiopulmonary resuscitation. PMID- 8487439 TI - Cardiopulmonary resuscitation. PMID- 8487440 TI - Cardiopulmonary resuscitation. PMID- 8487441 TI - Cardiopulmonary resuscitation. PMID- 8487442 TI - Cardiopulmonary resuscitation. PMID- 8487443 TI - Renal disease in hypertensive blacks: MRFIT. PMID- 8487444 TI - Renal disease in hypertensive blacks: MRFIT. PMID- 8487445 TI - An assessment of radical prostatectomy. Time trends, geographic variation, and outcomes. The Prostate Patient Outcomes Research Team. AB - OBJECTIVES: To examine temporal trends and geographic variation in radical prostatectomy rates and short-term outcomes. DESIGN: Population-based study of radical prostatectomy for the years 1984 through 1990. Poisson regression was used to estimate temporal and regional effects. SETTING: The 50 states and the District of Columbia. PARTICIPANTS: A 20% national sample of male Medicare beneficiaries aged 65 years or older. MAIN OUTCOME MEASURES: Rate of radical prostatectomy; 30-day mortality; and major cardiopulmonary complications, vascular complications, or surgical repairs within 30 days of radical prostatectomy. RESULTS: A total of 10,598 radical prostatectomies were identified. The adjusted rate of radical prostatectomy in 1990 was 5.75 times that in 1984. The relative increase was similar in all age groups. Substantial geographic variation existed in rates from 1988 through 1990: all states in the New England and Mid-Atlantic regions had rates equal to or below 60 per 100,000 male Medicare beneficiaries, while all states in the Pacific and Mountain regions had rates equal to or above 130 per 100,000. The mortality and morbidity after radical prostatectomy are not trivial for older men (aged 75 years and older)- almost 2% died and nearly 8% suffered major cardiopulmonary complications within 30 days of the operation. CONCLUSION: The sharp increase and wide geographic variation in radical prostatectomy rates make the evaluation of this surgical procedure a pressing issue. The rising rate of radical prostatectomy among men aged 75 years and older merits special attention. PMID- 8487446 TI - Estrogen replacement therapy and cognitive function in older women. AB - OBJECTIVE: To determine whether replacement estrogen delays or prevents loss of cognitive function in elderly women. DESIGN: A 15-year prospective and cross sectional study. SETTING: Rancho Bernardo, a geographically defined community in Southern California. PARTICIPANTS: Eight hundred women (80% of local surviving women from the original Rancho Bernardo cohort) aged 65 to 95 years. Estrogen use was evaluated at baseline between 1972 and 1974 and at follow-up between 1988 and 1991. MAIN OUTCOME MEASURES: Twelve tests of cognitive function from eight standard instruments administered at follow-up between 1988 and 1991. RESULTS: Almost half of this older, educated cohort had used estrogen at some time after menopause, and one third were current users. The age-related decrement in cognitive function was similar for women who were current, past, or never users of estrogen. Age- and education-adjusted comparisons also failed to show any consistent association between performance on tests of cognitive function and baseline, past, current, or never estrogen use; estrogen dose; or duration of use. Among 132 statistical comparisons, only five statistically significant differences were observed, less than the number expected by chance alone. Furthermore, these significant differences occurred with different tests of cognitive function, and in only one instance was the better test score associated with current estrogen use. No biases were identified that could explain these negative results. CONCLUSIONS: No compelling or internally consistent evidence for an effect of estrogen on cognitive function was found in these older women. These data do not support the hypothesis that estrogen use after the menopause preserves cognitive function in old age. PMID- 8487447 TI - Racial differences in the use of revascularization procedures after coronary angiography. AB - OBJECTIVE: To assess whether rates of coronary revascularization procedures differ between blacks and whites after coronary angiography is performed and to assess the relationship of these rates to hospital characteristics. DESIGN: A retrospective cohort study using 1987 and 1988 data on hospital claims and characteristics from the Health Care Financing Administration. SETTING: One thousand four hundred twenty-nine acute care hospitals that provide coronary angiography in the United States. PATIENTS: A national sample of 27,485 Medicare Part A enrollees, aged 65 to 74 years, who underwent inpatient angiography for coronary heart disease in 1987. MAIN OUTCOME MEASURE: The adjusted odds of revascularization with either coronary angioplasty or bypass graft surgery within 90 days of angiography for whites relative to blacks, controlling for age, sex, region, Medicaid eligibility, principal diagnosis, comorbid diagnoses, and hospital characteristics of ownership, teaching status, urban/suburban or rural location, and availability of revascularization procedures. RESULTS: White men and women were significantly more likely than black men and women, respectively, to receive a revascularization procedure after coronary angiography (57% and 50% vs 40% and 34%, both P < .001). The adjusted odds of receiving a revascularization procedure after coronary angiography were 78% higher for whites than blacks (95% confidence interval for odds ratio, 1.56 to 2.03). Statistically significant racial differences in the adjusted odds of receiving a revascularization procedure were present in all types of hospitals except rural hospitals, and these differences did not vary significantly by any of the four hospital characteristics (all P > .20 for interaction terms). CONCLUSIONS: Among Medicare enrollees, whites are more likely than blacks to receive revascularization procedures after coronary angiography. Racial differences of similar magnitude occur in all types of hospitals. These differences may reflect overuse in whites or underuse in blacks, but they are unlikely to reflect access to cardiologists or hospitals that perform revascularization procedures. Potential explanations include unmeasured clinical or socioeconomic factors, differing patient preferences, and racial bias at the hospitals performing angiography. PMID- 8487448 TI - Case-by-case assessment of recoverable materials for overseas donation from 1318 surgical procedures. AB - OBJECTIVE: To provide a mechanism for addressing the need for consistency and projection in overseas donation of surgical supplies, we conducted a case-by-case inventory of unused materials recovered from all surgical procedures in our facility over a 2.5-month period. DESIGN: Unused surgical supplies were recovered in coded bags from individual cases and inventoried. SETTING: Inpatient operating rooms at Yale-New Haven Hospital. MAIN OUTCOME MEASURE: The weight and dollar value of recovered materials were tallied for each case type; these were then extrapolated according to the frequency with which each procedure is performed in the United States to provide an estimate of the impact of a nationwide recovery program. RESULTS: The value of supplies recovered ranged from $1 (bone marrow transplant) to greater than $40 (liver and vulva/perineum procedures). By extrapolation to case-specific data from the National Hospital Discharge Survey (1990), we estimate that a nationwide recovery program could yield more than $193 million in charitable material and reduce operating room waste by more than 1.7 million kilograms (1948 tons). CONCLUSIONS: Consistency and organization would contribute greatly to efforts to alleviate existing medical supply needs in the developing world. This case-by-case assessment should enable participating centers to project more effectively the outcome of such collections and allow the coordination of efforts. Though unlikely to be adopted by all operating theaters in the United States, the potential charitable contributions from a nationwide recovery program are significant. PMID- 8487449 TI - A decision analysis of alternative treatment strategies for clinically localized prostate cancer. Prostate Patient Outcomes Research Team. AB - OBJECTIVE: To model the impact of initial therapy on outcomes for men with localized (clinical stage A or B) prostatic carcinoma. DESIGN: A decision analysis modeling three strategies: radical prostatectomy, external-beam radiation therapy, and watchful waiting, with delayed hormonal therapy if metastatic disease develops. We modeled the main benefit of treatment as a reduction in the chance of death or disutility from metastatic disease. These benefits were offset in the model by the risks of treatment-related morbidity and mortality. The model was used to analyze expected outcomes by tumor grade (well, moderately, and poorly differentiated) for men 60 to 75 years of age. DATA: Probabilities and rates for important clinical events, obtained through review of the literature for prostatic carcinoma and analysis of Medicare claims data. MAIN RESULTS: Several patterns emerged within the range of uncertainty about the risks and benefits of treatment for prostatic carcinoma. In patients with well differentiated tumor grades, based on clinical staging, treatment at best offers limited benefit in terms of quality-adjusted life expectancy and may result in harm to the patient. Among patients with moderately or poorly differentiated tumors, if we use the most optimistic assumptions about treatment efficacy, then patients aged 60 to 65 years would benefit from either radical prostatectomy or external-beam radiation therapy, compared with watchful waiting. However, in most other cases, treatment offers less than a 1-year improvement in quality-adjusted life expectancy or decreases the quality-adjusted life expectancy compared with watchful waiting. Invasive treatment generally appears to be harmful for patients older than 70 years. CONCLUSIONS: Radical prostatectomy and radiation therapy may benefit selected groups of patients with localized prostate cancer, particularly younger patients with higher-grade tumors. However, our model shows that in most cases the potential benefits of therapy are small enough that the choice of therapy is sensitive to the patient's preferences for various outcomes and discounting. The choice of watchful waiting is a reasonable alternative to invasive treatment for many men with localized prostatic carcinoma. PMID- 8487450 TI - Why estimates of physician supply and requirements disagree. AB - OBJECTIVE: To review the major forecasts of physician supply and physician requirements. DATA SOURCES: English-language medical literature on physician manpower published between 1980 and 1990, identified from journal articles selected through searches of the MEDLINE and Health Planning and Administration databases using the search formulations physician supply, health manpower- physicians, and physician manpower. STUDY SELECTION: Sources were selected if they were repeatedly cited and provided quantitative projections. DATA EXTRACTION: Each study was reviewed for its quantitative projections and to identify its methodological assumptions. DATA SYNTHESIS: All forecasts point to a steadily increasing physician supply and, with one exception, suggest that supply will exceed requirements in the year 2000. The estimates of physician supply across studies varied primarily because of differing assumptions about entrance rates into the profession and the size and clinical work load of specific categories of physicians: researchers, teachers, administrators, residents, and women. The estimates of physician requirements were more volatile because of differences in the basic approach and assumptions about future growth and market structure. CONCLUSIONS: Even though the measurement of entrance and exit rates from the profession is a generally accepted approach to forecasting supply, apparently minor disagreements on assumptions create large discrepancies between forecasts over time. There is no accepted approach to forecasting physician requirements. PMID- 8487451 TI - Screening for adolescent idiopathic scoliosis. Policy statement. US Preventive Services Task Force. PMID- 8487452 TI - Screening for adolescent idiopathic scoliosis. Review article. US Preventive Services Task Force. PMID- 8487453 TI - The safety of tricyclic antidepressants in cardiac patients. Risk-benefit reconsidered. PMID- 8487454 TI - Evidence-based practice guidelines from the US Preventive Services Task Force. PMID- 8487455 TI - Hypertension in pregnancy: preeclampsia-eclampsia. AB - Diagnosis of preeclampsia involves consideration of many different factors. It is desirable to make the diagnosis early in the disease course for the best possible outcome for mother and fetus. Overdiagnosis may occur in some cases; however, given the severe maternal and fetal morbidity in cases of untreated disease, it is best to monitor and treat symptoms before they become severe. Overall goals of treatment include prolonging the pregnancy as long as possible without compromise of maternal health, while monitoring the fetus for signs of distress. Treatment for the mother is symptomatic, with seizure prophylaxis and hypertension control. In gestations less than 32 weeks, it is desirable to expose the fetal lungs to at least 48 hours of corticosteroids before delivery to enhance lung maturity. Studies of preeclampsia have demonstrated high fetal morbidity/mortality for gestations less than 24 weeks. With expectant management, decreased fetal morbidity and mortality are shown for both 24- to 27- and 28- to 34-week gestations. Secondary to excellent fetal survival, immediate delivery is indicated for severe disease at gestation greater than 34 weeks. PMID- 8487456 TI - Norplant: a welcome new contraceptive. PMID- 8487457 TI - Declining incidence of Haemophilus meningitis in Kansas. PMID- 8487458 TI - Does 'front-loading' with rt-PA improve treatment of acute myocardial infarction? PMID- 8487459 TI - Without a clout. PMID- 8487461 TI - Fiduciary duties. PMID- 8487460 TI - What a year this has been! PMID- 8487462 TI - [Tarsoconjunctival advancement--a surgical procedure in cicatricial entropion with marginal tarsus deformation]. AB - BACKGROUND: After severe chemical and thermal burns, and in chronic inflammatory conditions of the conjunctiva frequently scarring of the tarsal plate with distortion of the eyelid margin and keratinization of the tarsal conjunctiva could be found. This condition is accompanied with chronic inflammation and malposition of the eyelids resulting in entropion and trichiasis. PATIENTS AND METHODS: A surgical procedure is introduced separating the scarred and shortened tarsal plate from the cutis-muscle sheet. After excision of tarsal scar tissue and of the marginal metaplastic tarsus a new eyelid margin is formed by tarso conjunctival advancement, correcting trichiasis and cicatricial entropion. During the time from August 1984 to December 1991 this surgical procedure was conducted on 16 patients, correcting 18 upper and 4 lower eyelids. 11 patients suffered from severe chemical and thermal burns, 2 patients from Stevens-Johnson-syndrome, 2 patients from ocular pemphigoid and 1 patient from herpes zoster infection. RESULTS: All patients were examined at least once in the first 6 postoperative months, 11 patients are still under continuing outpatient review. The mean follow up time is 27 months, the minimum follow-up period is 7 months. In 7 patients the surgical procedure prepared conditions for a successful keratoplasty and in 5 other cases the keratopathy healed. In 4 cases a recurrence of the entropion occurred (18% recurrence rate). CONCLUSIONS: The presented surgical procedure is a promising alternative to more complicated procedures for correcting cicatricial entropion with keratinization of the marginal tarsus. PMID- 8487463 TI - [Ocular complications of long-term survival of bone marrow transplantation. A prospective study with 21 patients]. AB - BACKGROUND: Survival time after bone marrow transplantation is getting increasingly longer and secondary ocular complications need to be identified and deserve more attention as so far. PATIENTS AND METHODS: We evaluated the ocular complications of 21 not selected, long-term survivors after bone marrow transplantation in a prospective study. The ophthalmological examination consisted of visual acuity, slit lamp examination, tonometry and ophthalmoscopy. It included also determination of tears break-up-time, Jones-test, rose bengal staining and impression cytology of the conjunctiva. RESULTS: The major ocular complication was the development of a keratoconjunctivitis sicca syndrome in 14 of the 21 patients. This complication is probably due to the total-body irradiation in the preparative before and to the development of a chronic Graft versus-Host-Disease after transplantation. 13 of the 21 patients developed a cataract. This might be a result of the total-body irradiation and a prolonged high steroid intake. CONCLUSION: The frequency and severity of ocular complications suggest that detailed ocular examinations should be performed routinely in patients after bone marrow transplantation. PMID- 8487464 TI - [Visual compromise of automobile drivers by frontal photo-flash in mesoptic conditions]. AB - The time for recovery of recognition of an optotype presented at a distance of 40 m subsequent to exposure to a flash gun (Eso company, Tettnang; flash energy 200 Ws, duration 1/1000 s; distance 10 m) was studied on 97 subjects aged 20 to 83 years. A Landolt-ring (contrast 1:5, diameter 29 cm), mounted on a disk (diameter 58 cm) which could be rotated in steps of 45 degrees served as a test target. The flash gun could be dimmed down by a red filter (Schott RG 665). The tests were performed at night without additional illumination except the low beam of the car. The flash gun was foveally fixated. After a white flash, a period of 93.1 s +/- 48.6 s (MEAN +/- SD) passed before the optotype could be recognized correctly again. By adding the red filter in front of the flash gun the recovery time could be shortened significantly (p < 0.0001; Wilcoxon signed-rank test) to 4.9 s +/- 1.7 s. "Time for re-adaptation" after dazzling by red flash is comparatively short and therefore strongly influenced by many variables (e.g. time for recognition and for verbalization). Because of that a final evaluation of dazzling by red flash seems to be impossible with this method. Subjects of advanced age and opacities of the ocular media showed an increase in the "time for re-adaptation" for the white as well as the red flash. In conclusion, a speed control using white flash guns at night can be considered as critical. PMID- 8487465 TI - [Clinical use of the excimer laser in treatment of surface corneal opacities- therapeutic strategy and case reports]. AB - BACKGROUND: The authors report on the Phototherapeutic 193nm-Excimer Laser Keratectomy (PTK) for the treatment of superficial corneal opacities. MATERIAL AND METHOD: In two cases with corneal opacities after contact lens wearing and after therapy resistant keratoconjunctivitis epidemica respectively the treatment strategy is presented. The epithelium and the corneal opacities are removed mechanically as far as possible. Then the Excimer laser smoothing with masking fluids of different viscosity is performed. RESULTS: In both patients the visual acuity improved from 1/50 and 0.16 respectively to 0.7. Both eyes had an hyperopic shift. The patients were without pain within a follow-up period of 8 months after treatment. CONCLUSION: The phototherapeutical use of the 193nm Excimer laser to treat superficial corneal opacities can be regarded as a real alternative to conventional surgical techniques. PMID- 8487466 TI - [Development of endocrine orbitopathy in pregnancy]. AB - A report is given on an endocrine orbitopathy in a 24-year-old female in which the disease deteriorated from the 3rd month of pregnancy, with a severe restriction of motility, exophthalmia (Hertel exophthalmometer both eyes 28 mm), severe visual field defects and a decrease of visual acuity to 20/200 both eyes. Therefore--despite of certain restraints of the pharmacologic therapy during pregnancy--glucocorticoid-treatment was started. After delivery, the condition deteriorated, despite of a higher steroid dose. Therefore, a retrobulbar irradiation was begun on the 12th day post partum (telecobalt 10 Gy). From that time on all signs improved over the next months (visual acuity 20/25; exophthalmometer both eyes 20 mm, normal visual field). In the literature, endocrine orbitopathy (Graves' ophthalmopathy) during pregnancy has been mentioned sporadically, but to our knowledge such a severe case, as reported here, has not been described before. PMID- 8487467 TI - [Spontaneous dislocation of a silicone disk lens 4 months postoperative into the vitreous body]. AB - We report on a patient who experienced an acute deterioration in visual acuity at night four months after implantation of a silicon-disc lens into the capsular bag. On examination, the artificial lens was localized preretinally. The capsular equator was fibrous, but had retained its circular shape. The posterior capsule was ruptured. The rupture may be explained by tension in the posterior capsule, which is only 1-4 microns thick, within the shrunken capsular bag, and by an acute increase of intraocular pressure caused by rubbing of the eyes during sleep. PMID- 8487468 TI - [3 cases of vertical accommodative vergence]. AB - Three cases of vertical accommodative vergence have been observed. One patient is described in detail. His right eye had become blind after a trauma. He showed a vertical vergence triggered by accommodation that had not been seen before his loss of sight. The strabismic eye deviated upwards during desaccommodation and downwards during accommodation. This unusual phenomenon could be due to a congenital supranuclear abnormality which became apparent only after the loss of binocular vision. PMID- 8487469 TI - [An illuminated orbital spatula--possibilities for use in ophthalmology]. AB - Illumination sometimes becomes a problem during ophthalmic surgery, especially in retroequatorial myopexia (Fadenoperation). The common headlights use to reduce the mobility of the surgeon. We present a modified SAUTTER's orbita spatula, which is armed with a fibre-optic. It can be connected with a commonly available cold-light-source. The prototype can been used in the following surgical procedures, retroequatorial myopexia (Fadenoperation) demonstrated by photograph: tendon tucking of the superior oblique, retinal detachment surgery, orbital tumors. Several surgeons regarded the optimal illumination of a difficult surgical situs as an improvement. With some modifications of the prototype which are prepared now the illuminated orbital spatula should become a useful instrument for the ophthalmic surgeon. PMID- 8487470 TI - [Developments in ophthalmologic electrophysiology]. AB - During the last years electrophysiology in ophthalmology has been facilitated to a big extent by computerized methods. Thus it has become a suitable method for an increasing number of relevant diagnostic problems. To make comparisons between test results of different diagnostic places easier an international standard concerning the methodology of the electroretinogram (ERG) has been elaborated by the "International Society of Clinical Electrophysiology in Vision" (ISCEV). Aim of the present article is to give a short description of the ERG-standard and to review recent developments in clinical electrophysiology in ophthalmology (ca. since 1989). PMID- 8487471 TI - [Teratoma of the orbit]. PMID- 8487472 TI - [Recollections of Hans Goldmann, 1899-1991]. AB - Professor Hans Goldmann died in Bern on November 19th, 1991 at the age of 91 years. His outstanding intellectual capacity was discovered at an early age and demonstrated throughout his life. He was appointed as teaching assistant of the famous A. Cermak von Seysenegg, Chairman of the Institute of Physiology of the German Charles University in Prague. During his stay at the University of Prague, he was influenced by the famous people of his time, such as Einstein (physicist), Mach (physicist and psychophysicist), Lorenz (behavioral scientist), Popper (philosopher), Schlick (physicist and philosopher), Hering (physiologist), and others. Goldmann absorbed the essence of these disciplines to a very large extent. This, together with his remarkable intellect, enabled him to produce outstanding research work within a large spectrum of sciences more or less directly related to ophthalmology. Goldmann became known in particular for his exceptional and fundamental work on perimetry and glaucoma and he managed to cast his basic insight into practical, easy-to-operate, high-precision diagnostic instruments which, several decades after their invention, are still used by every ophthalmologist. He will enter history as one of the very great pioneers in ophthalmology. PMID- 8487473 TI - [Treatable diseases of the nervous system with cataract formation]. AB - The detection of a cataract in combination with a neurological deficit may provide the physician with important diagnostic help. But a minority of underlying diseases (angiokeratoma corporis diffusum, cerebrotendinous xanthomatosis, diabetes mellitus, galactosemia, hypocalcemia, Refsum's disease, Wilson's disease; Charles Bonnet syndrome; relapsing Perichondritis; adverse effects of medication and intoxications) can be treated causally. Therefore they are summed up and discussed in this paper. PMID- 8487474 TI - [Do pilots need stereopsis ?]. AB - Pilots so far are required to have a good quality of stereopsis. Many people do not meet this requirement. But is this requirement justified by research in aviation medicine and psychology of perception? This question is discussed on the basis of the theoretical and empirical literature. The answer is: No. PMID- 8487475 TI - [Tongue ultrasound and pressure measurement in infantile sucking. Initial results]. AB - The sucking procedure was examined in 10 healthy, term infants and in one newborn with disturbed sucking actions suffering from recurrent aspiration pneumonia. We applied ultrasonography of the tongue and simultaneous intraoral pressure measurements in the examinations. Observations were made with a bottle feeding system (NUK). Sonography and intraoral measurements both gave reliable informations. Parallel recordings of tongue dorsum movements by pseudo-3 dimensional imaging and simultaneously obtained pressure curves show, that increasing suction is maintained by withdrawing the tongue dorso-cranially. Computer-aided evaluation of ultrasound images and pressure data demonstrate the possibility to distinguish between coordinated and uncoordinated sucking movements. Simultaneous use of both examination techniques can be helpful in diagnosis and documentation of disturbed sucking actions. PMID- 8487476 TI - [Accuracy of measurements of Kontrol 7840, Nellcor N200 and Radiometer OX13 pulse oximeters in infants and young children]. AB - Comparative validation studies of pulse oximeters from different manufacturers have predominantly been performed in adult patients. However, due to differences in the patient-sensor interface, the results from those studies may not be transferable to the paediatric population. We therefore performed 123 simultaneous measurements (37 patients) of transcutaneous O2-saturation (StcO2) from 3 pulse oximeters and compared these with the arterial O2-saturation (SaO2) from a co-oximeter (Radiometer OSM 3). The median age of the 37 patients at the time of study was 2.0 months (range 1 day-5 years), their weight 4.7 kg (0.8-15.0 kg). The mean difference between StcO2 and SaO2 was -0.6% (SD 5.2%) for the Kontron 7840 pulse oximeter, -0.9% (SD 2.3%) for the Nellcor N200, and -1.2% (SD 3.5%) for the Radiometer OXI3 pulse oximeter. The corresponding 95% intervals were -7.4(-) + 9.6%, -5.7(-) + 4.3% and -7.0(-) + 6.3% for the Kontron, Nellcor and Radiometer instrument, respectively. These results demonstrate that neither of the 3 instruments systematically under- or overestimated SaO2. However, there were differences in precision, particularly in the low range of SaO2. PMID- 8487477 TI - [Is reliable blood glucose determination in the newborn infant possible with the small reflectance meter Reflolux S?]. AB - With the reflectance meter Reflolux S (Accucheck III) high as well as low blood glucose levels can be determined with excellent precision irrespective of the sample's hematocrit value. Within the range from 20-50 mg/dl we found an average deviation from the expected value of less than 2 mg/dl; in selected samples, however, a difference of up to 10 mg/dl was recorded. The scatter can be explained by the influence of hematocrit values on the results. An increase of 10% in hematocrit lowered the measured glucose value by approximately 10%. At glucose concentrations below 40 mg/dl and in the presence of high resp. low hematocrit values any results obtained with this glucose meter will only have screening character; they should be re-run using an established method. PMID- 8487478 TI - [Epiphysiolysis capitis femoris as a possible complication of hypoparathyroidism in partial Di George syndrome]. AB - We report on a 2-year old boy with the characteristic features of Di George syndrome. The diagnosis was confirmed by history, biochemical, immunologic and radiologic findings. After physical exercise he developed an unilateral epiphysiolysis capitis femoris, rarely seen in this age and not known to be a complication of hypoparathyroidism. PMID- 8487479 TI - [Congenital lipoid hyperplasia of the adrenal gland and male pseudohermaphroditism: clinical aspects of two siblings]. AB - Two siblings of consanguinous parents, one male and one female, presented with symptoms of adrenal insufficiency related to respiratory infection at the age of two and three months, respectively. Besides a reduction of the synthesis of gluco and mineralocorticoids, the sexual hormones were found to be reduced as well. Therefore, the boy showed a female sexual phenotype (male pseudohermaphroditism). Additionally, minor malformations including epicanthal folds, anti-mongoloid palpebral fissures, low-set ears were noticed, which have not been reported in children with the suspected diagnosis previously. The female sibling had typical Addison's crisis twice during the following years. Endocrinological tests yielded evidence for Cholesterol-20,22-desmolase deficiency. PMID- 8487480 TI - [Glutaric acidemia/glutaric aciduria I as differential chorea minor diagnosis]. AB - Glutaracidemia/glutaraciduria type I is an acute or subacute neuropathic disorder of infancy or early childhood. The following symptoms characterize the clinical course: macrocephalus present at birth, cerebral atrophy revealed by CT or MRI scans, most striking in the frontal and temporal lobes, choreoathetosis and dystonia as neurological handicaps. The deficiency of glutaryl-CoA-dehydrogenase leads to glutaracidemia and glutaraciduria. It is reported on a three year old girl. The glutaraciduria is an important differential diagnosis to chorea minor. PMID- 8487481 TI - [Tetra-X syndrome with epilepsy, mental retardation and multiple dysmorphias]. AB - It is reported on a 21-year-old female with super-female syndrome in association with an early childhood brain damage exhibiting idiopathic epilepsy, severe oligophrenia, emotional instability, Little syndrome, areflexia of the legs, strabismus, telecanthus, broad nose, epicanthic fold, clinodactyly of little fingers, radio-ulnar-synostosis, retardation of ossification, aortic insufficiency, erythro-cyanosis, one-side clubfoot and nephrosclerosis, also menstrual cycle dysfunction. PMID- 8487482 TI - "Changing concepts in the treatment of congenital diaphragmatic hernia". PMID- 8487483 TI - [Surfactant therapy in severe neonatal respiratory failure--multicenter study--I. Surfactant therapy in 264 premature infants of < 34 weeks with IRDS with special reference to "non-responders"]. AB - As a part of a west german multicenter study (16 hospitals) 264 preterm neonates < 34 gestational weeks were treated with bovine surfactant (Alveofact, 50-200 mg/kgBW). Entry criterion was need of mechanical ventilation and FiO2 of > 0.5. Compared with a previous prophylactic study with the same surfactant product these patients were slightly more mature (median: 29 gestational weeks, 1260 g) but had a higher oxygen demand at the time of treatment (median FiO2: 0.82). Survival rate (28. d) was 82%. At this time 38% showed spontaneous respiration without, 16% with additional oxygen. The incidence of pulmonary interstitial emphysema was 22%, of pneumothorax 13%, and of PDA 33%. Severe intracranial hemorrhage (grade III or IV according to Papile) had 25%, ROP (any grade) 27%. Nonresponder showed a higher initial FiO2 of 0.94. With regard to umbilical artery pH, mode of delivery, birth weight, and maturity) they were similar to the responders. We did not find a parameter, by which we could predict the response to surfactant. PMID- 8487484 TI - [Surfactant therapy in severe neonatal respiratory failure--multicenter study- II. Surfactant therapy in 10 newborn infants with meconium aspiration syndrome]. AB - As a part of a west german multicenter study (424 patients, 16 hospitals) 10 term neonates ventilated because of severe meconium aspiration syndrome were treated with 1-4 doses of 50 mg/kg/BW of a bovine surfactant (Alveofact). Before treatment respiratory distress was severe (median FiO2: 1.0, median MAD 9.9 mmHg, median OI: 20). Acute improvement ("responders") was shown in 4 patients. All patients survived. Time of mechanical ventilation was 6-26 d. High frequency ventilation was applied in two nonresponders, ECMO in one. PMID- 8487485 TI - [Surfactant therapy in severe neonatal respiratory failure--multicenter study- III. Surfactant therapy in 41 premature infants < 34 weeks with suspected congenital infection (case-control analysis)]. AB - As a part of a multicenter study (424 patients, 16 hospitals) 41 ventilated very low birth weight infants (24-33 gestational weeks, 640-1560 g), who were suspected to have connatal pneumonia, were treated with a bovine surfactant (Alveofact, 50-200 mg/kgBW). Using a case control design they were compared with 41 patients having IRDS. There were no differences between the collectives with regard to the acute response to surfactant, the clinical course, and the outcome at the 28. d of life. Accidental treatment with natural surfactant in very immature neonates suffering from severe respiratory distress due to connatal pneumonia resp. connatal pneumonia accompanying IRDS seems not to harm these patients. PMID- 8487486 TI - [Effect of organized general preventive administration of iodized salt on struma incidence and ioduria in 11-16-year-old children in the Jena endemic area]. AB - In 1988 and in 1991, i.e. two and five years after the introduction of a general iod salt supply (32 mg KJO2/kg salt) in our region, we investigated the frequency of goiters and the level of iodine excretion in urine in 504 and 336 school children of 11 to 16 years of age. In 1988 the assessment of goiter size was made by inspection and palpation according to the recommendation of WHO. 36% of the school children were found to have goiters of type I b or II. The average urine excretion of iodine amounted to 46.2 +/- 37.2 micrograms Iod/g creatinine (n = 353). In 1991 we selected school children with goiters by the same criteria and found frequency (34%) to be nearly unchanged compared to 1988. Furthermore we investigated these goiters with ultrasound and confirmed the diagnosis in 100 from 107 children. The average daily urine excretion of iodine was significantly higher in 1991 (57.7 +/- 24.8 micrograms/Iod/g creatinine, n = 328) than in 1988. However this value is below the level recommended by the WHO (minimum 75 micrograms Iod/g creatinine). Despite the increase of the iodine intake over the last years, the frequency of goiters in pubertal school children in the Jena region is endemic. This fact supports the demand for a general and sufficient iodine supply. PMID- 8487487 TI - [Secretory immunoglobulin A in childhood: does the saliva value reflect the bronchial value?]. AB - Immunoglobulin A (IgA) can be found in different body secretions and plays a major role in the local immune response. It inhibits bacterial adherence, neutralizes toxins and protects the mucosa from penetrating antigens and allergens. Whereas measurement of IgA in saliva mostly does not show any problems, difficulties in assessing IgA in bronchial fluids often occur mainly due to variable dilutional effects. Aim of the present study was to find out whether saliva IgA predicts bronchial IgA. In 15 children aged 4 months to 14 years (mean 53.5 months; SEM 12.3) with chronic cough (n = 10), mediastinal mass (n = 1), recurrent airways obstructions (n = 2) and inspiratory stridor (n = 2) we performed a diagnostic rigid bronchoscopy and assessed IgA by means of bronchial lavage (BL). We attempted to control for uncertain dilution by the use of albumin as a denominator and to present our data as ratios of IgA to albumin. As various disease states alter the integrity of the alveolar-capillary membrane and influence the concentration of albumin in the epithelial lining fluid we developed an optical score to describe the state of the bronchial mucosa. Measurement of saliva IgA is easy and can be done without dilutional effects. The mean value of IgA in saliva was 65.49 mg/l (SEM 14.75; range 3.5-227), the one of IgA in bronchial lavage fluid 30.75 mg/l (SEM 7.11; range 3.5-100). IgA-albumin ratio ranged from 0.006 to 1.46 (mean 0.36, SEM 0.12). Saliva IgA did neither significantly correlate with bronchial IgA nor with bronchial IgA-albumin ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487488 TI - [The protective effect of theophylline in exercise-induced asthma in childhood]. AB - In order to study the protective effect of theophylline on exercise-induced asthma in children, we investigated the lung function of 16 children with documented bronchial asthma. Exercise provocation was performed by running on a treadmill for 6 minutes before and after two dose regimens of theophylline (10 and 20 mg/kg body weight). While for FEV1 the low dose regimen only showed a trend (p < 0.1), there was a slight but significant improvement in the high dose regimen (p < 0.05). Concerning sRaw both groups showed a small but significant improvement compared with the baseline values (p < 0.05). We conclude that in addition to its bronchodilatory effect theophylline may modulate exercise induced bronchospasm in asthmatic children. PMID- 8487489 TI - Controlled diet in phenylketonuria may cause serum carnitine deficiency. AB - Serum carnitine levels may be reduced in patients with phenylketonuria (PKU) owing to low carnitine intake, deficient carnitine synthesis and acylcarnitine production from phenylalanine metabolites. In order to investigate the possible carnitine deficiency we determined serum carnitine in its different forms and the precursors and cofactors involved in its synthesis in a group of patients with PKU or hyperphenylalaninaemia. Free, total and acylcarnitine values were significatively reduced only in PKU patients with Phe-restricted diet which had not been supplemented with carnitine. Acylcarnitine/free carnitine ratio and all the other parameters studied were normal in all patients. We conclude that the low serum carnitine levels in PKU patients with a strict diet are a consequence of the low carnitine intake. PMID- 8487490 TI - Plasma phenylalanine and tyrosine levels revisited in heterozygotes for hyperphenylalaninaemia. AB - We examined the value of the fasting plasma phenylalanine/tyrosine ratio obtained in an ordinary clinical setting for assessing the probability of being a heterozygote for hyperphenylalaninaemia. This biochemical test was found to be of little value in those with a high (66%) prior risk of heterozygosity, because it could not reduce the risk below 12%. However, in a population with a prior risk of only 2%, it discriminates the 3% with a 19% risk from the 97% with a risk of 1.5% or less. This simple method could usefully be applied to such a population, in order to select those at higher risk for further investigation using molecular genetics. PMID- 8487491 TI - The use of gelatin capsules for ingestion of formula in dietary treatment of maternal phenylketonuria. AB - Maternal phenylketonuria (PKU) represents a high risk for birth defects, including mental retardation, in offspring. Thus, it could cancel gains represented by the prevention of PKU-induced mental retardation in the current generation. Effective dietary treatment of maternal PKU pregnancies could avoid this potentially tragic occurrence. However, dietary compliance is often difficult because a necessary component of the diet, medical nutritional formulas, often have an unpleasant taste and odour. We treated the second pregnancy of a phenylketonuric women who had required extended hospitalization during her first pregnancy because of poor formula tolerance, and who had similar difficulty in the second pregnancy. To alleviate this problem, we developed a system whereby she could pack the formula into gelatin capsules for ingestion. Packing and ingestion of 20 capsules required less than 30 minutes three times a day. With capsules her blood phenylalanine level was almost always within the recommended range of 120-360 mumol/L (2-6 mg/dl) and hospitalization was not required. The phenylalanine content of the capsules was easily accommodated by a small reduction in allowable food. Other amino acid levels, including tyrosine and other essential nutrient levels, were normal. We believe that using gelatin capsules for formula ingestion can be very beneficial in the management of maternal PKU pregnancies and could be extended to the dietary treatment of other inborn errors of metabolism. PMID- 8487492 TI - Identification of N-acetyl-alpha-aminoadipic acid in the urine of a patient with alpha-aminoadipic and alpha-ketoadipic aciduria. AB - A 3.5-year-old Japanese boy with a mild speech disturbance excreted a large amount of alpha-aminoadipic acid into the urine. The amino acid analysis using an amino acid analyser confirmed the presence of alpha-aminoadipic acid in both urine and plasma. We detected alpha-aminoadipic acid in the hydrolysate of the effluent and washwater fraction through cation exchange resin. This suggested the presence of acetylated derivatives and we identified N-acetyl-alpha-aminoadipic acid using liquid chromatography-atmospheric pressure ionization mass spectrometry (LC-API-MS). The concentrations of alpha-aminoadipic acid and N acetyl-alpha-aminoadipic acid in the urine of a patient with alpha-aminoadipic aciduria were 376.9 nmol/mg creatinine and 18.1 nmol/mg creatinine, respectively. We also detected alpha-ketoadipic acid in the urine of this patient using LC-API MS. PMID- 8487493 TI - The effect of lovastatin on very low-density lipoprotein apolipoprotein B production by the liver in familial combined hyperlipidaemia. AB - Overproduction of very low-density lipoprotein apolipoprotein B by the liver is a metabolic marker for familial combined hyperlipidaemia, a common inherited disorder of lipoprotein metabolism. Four subjects with familial combined hyperlipidaemia had rates of apolipoprotein B production which were 2-7 times normal, using a protocol in which [15N]glycine was used to label newly synthesized hepatic proteins. Following 4-6 months of therapy with lovastatin, very low-density lipoprotein apolipoprotein B production in all four subjects had returned to the normal range. This demonstrates that lovastatin, an inhibitor of cholesterol biosynthesis, acts also to reduce the apparent production rate of apolipoprotein B by the liver. PMID- 8487494 TI - Inhibition of succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase activities by methylmalonate in brain and liver of developing rats. AB - The effects of methylmalonate (MMA) on succinate dehydrogenase (SDH) and beta hydroxybutyrate dehydrogenase (HBDH) activities in brain and liver of 15-day-old rats were studied. The apparent Km of SDH for succinate was 0.45 mmol/L in brain and 0.34 mmol/L in liver. MMA inhibited the enzyme activity in both tissues with Ki values of 4.5 mmol/L and 2.3 mmol/L in brain and liver, respectively, and the inhibition was of the reversible competitive type. The calculated Km for HBDH with beta-hydroxybutyrate as substrate was 1.26 mmol/L in brain and 0.36 mmol/L in liver. MMA inhibited the enzyme with a Ki value of 0.015 mmol/L in brain and 0.275 mmol/L in liver. These results are probably relevant to our understanding of cerebral metabolism in methylmalonic acidaemic children, especially during ketoacidotic and hypoglycaemic crises, and may be related to the pathogenesis of cerebral dysfunction of methylmalonic acidaemia. PMID- 8487495 TI - Formiminoglutamic/hydantoinpropionic aciduria in two siblings. PMID- 8487496 TI - Alcaptonuria in a Brazilian baby. PMID- 8487497 TI - Relation between phenotype and genotype in phenylketonuric patients from Bulgaria. PMID- 8487498 TI - Biochemical and immunological characterization of X-linked ichthyosis. AB - An immunoquantification protocol based on an enzyme-linked immunosorbent assay was developed to measure the abundance of the microsomal enzyme steroid sulphatase (STS). The two-step sandwich immunoassay is sufficiently sensitive to detect 100-200 pg purified steroid sulphatase in a 50-microliters sample. The steroid sulphatase content in fibroblast, leukocyte and placental extracts correlates with the steroid sulphatase activity in these extracts. No steroid sulphatase protein was found in approximately 350 micrograms plasma proteins from a normal person. In three of four X-linked ichthyosis patients a complete gene deletion was found by Southern hybridization with the full-length STS cDNA as probe. Neither steroid sulphatase protein nor enzymatic activity was found in fibroblast extracts of these three patients. In a fibroblast extract of another X linked ichthyosis patient, which had a normal Southern blotting pattern, no immunoreactive protein was detected. Residual activity of steroid sulphatase was also not found after prolonged incubation of this fibroblast extract with the natural substrate oestrone sulphate. PMID- 8487499 TI - Tissue distribution of mutant mitochondrial DNA in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). AB - We analysed the distribution of mutant mitochondrial DNA (mtDNA) with A-to-G substitution mutation of tRNA(Leu)(UUR) in various autopsied tissues from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS). There was no significant difference in the proportion (76 86%) of mutant mtDNA in many tissues, except in the lung and spleen. Unequal partitioning of mtDNA in somatic cells appears less prominent than that in germ cells. PMID- 8487500 TI - Review: the immunochemical analysis of enzyme from mucopolysaccharidoses patients. AB - The immunochemical analysis of enzyme from mucopolysaccharidoses (MPS) patients is aimed at defining the level and nature of the enzymically deficient protein produced by specific gene mutations. Immunochemical techniques allow purification of enzyme, characterization of the composite molecular species, measurement of cellular protein content, investigation of protein biosynthesis, determination of subcellular distribution, as well as information on protein structure and folding. This review focuses on the application of immunochemical techniques to the study of the aberrant protein produced in skin fibroblast cells derived from MPS patients. The analysis of enzyme protein has been applied to phenotype expression within single enzyme deficiency disorders. It is proposed that reliable prediction of MPS patient phenotype may require a combined approach utilizing immunochemical, biochemical, cell biological and gene analysis. However, this review will address the structure and nature of the protein produced in cells from MPS patients, the biological activity of this protein, and the incorporation of the protein into, and location within, subcellular fractions. PMID- 8487501 TI - Prenatal monitoring of ornithine transcarbamoylase deficiency in two families by DNA analysis. AB - We examined the DNA in two families with ornithine transcarbamoylase (OTC) deficiency. Two point mutations of the OTC gene, a C-to-T (codon 141) and a G-to A (codon 141), were identified. This allowed prenatal monitoring to be made for two fetuses in each family, using polymerase chain reaction (PCR), followed by allele-specific oligonucleotide hybridization or TaqI digestion of amplified sequence. The diagnoses showed heterozygotes of a wild type gene and the corresponding mutant gene in these fetuses; each was confirmed postnatally. PMID- 8487502 TI - Carbamoylphosphate synthetase deficiency in an adult: deterioration due to administration of valproic acid. AB - A 24-year-old patient had symptoms of lethargy, convulsions and hyperammonaemia during valproic acid therapy. Cessation of valproic acid treatment brought about an improvement both of the symptoms and of the hyperammonaemia. However, enzymatic analysis after the cessation of valproic acid therapy revealed a complete absence of carbamoylphosphate synthetase (CPS) activity in liver biopsy. A unique polypeptide band, corresponding to the control CPS protein in molecular weight ('CPS-like' protein), was found in normal amounts in the patient's liver on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. This CPS-like protein seemed to be more labile than the control, because the polypeptide band became faint after freeze-thawing. Intravenous administration of L-alanine resulted in a significant increase of serum urea and a transient increase of blood ammonia concentrations. These results strongly suggest that the patient has a labile CPS protein with no activity in vitro but some activity in vivo. We consider that valproic acid may have disrupted some metabolic adaptation by reducing N-acetylglutamate in the liver, which in combination with CPS deficiency induced severe hyperammonaemia. PMID- 8487503 TI - Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency: an inborn error of isoleucine and ketone body metabolism. AB - A review is presented of 22 published cases of verified or probable mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency, a disorder of isoleucine and ketone body metabolism. The clinical expression, characterized by ketoacidosis, vomiting and lethargy, is highly variable. Typical age of onset is between 6 and 24 months. The disorder, which has been observed in several ethnic groups, is apparently inherited as an autosomal, recessive trait. The prognosis is relatively good if acute episodes of ketoacidosis and dehydration are adequately treated. There is abnormal urinary excretion of 2-methyl-3-hydroxybutyric acid, tiglylglycine, and in some instances also 2-methyl-acetoacetic acid. However, such a pattern of organic aciduria has also been found in cases with normal thiolase activity. Genetic complementation analyses have demonstrated considerable heterogeneity. The cDNA for human methyl-acetoacetyl-CoA thiolase has been cloned and sequenced. Studies in one patient showed a G-to-A substitution at position 1138 of the mRNA, causing 347Ala to Thr change in the mature enzyme. Studies in other patients have shown variable enzyme amount and/or stability. PMID- 8487504 TI - Diagnosis of Zellweger syndrome by analysis of very long-chain fatty acids in stored blood spots collected at neonatal screening. PMID- 8487505 TI - Membrane-bound sorbitol dehydrogenase in human red blood cells. Studies in normal subjects and in enzyme-deficient subjects with congenital cataracts. AB - Membrane-bound and soluble forms of erythrocyte sorbitol dehydrogenase (SORD) activity are compared in normal individuals. Both isoenzymes showed similar properties. In a family with red cell SORD deficiency and congenital cataracts, Km values for sorbitol and NAD+ as well as the effect of the enzymatic deficiency on sorbitol accumulation in red cells incubated in high-glucose or high-fructose media were determined. In SORD-deficient patients, the enzymatic deficiency was observed in both crude haemolysate and SORD-M preparations with sorbitol, galactitol, xylitol or ribitol as substrates. The mutation responsible for SORD deficiency did not modify the Km for sorbitol and NAD+. Finally, SORD deficiency produced a significant increase of sorbitol accumulation in red cells incubated in high-concentration glucose media and a significant decrease when the cells were incubated in high-concentration fructose media. PMID- 8487506 TI - A possible case of transient hereditary fructose intolerance. AB - A patient is described who presented with the signs and symptoms of hereditary fructose intolerance a few hours after her first fructose challenge. The diagnosis was confirmed by the demonstration of reduced activity of hepatic aldolase B towards fructose-1-phosphate. A second liver biopsy 10 months later had normal aldolase B activity towards fructose-1-phosphate and a fructose tolerance test was also normal. A possible explanation for these findings is proposed. PMID- 8487507 TI - The effect of dietary fruits and vegetables on urinary galactitol excretion in galactose-1-phosphate uridyltransferase deficiency. AB - Even on a lactose-restricted diet, urinary galactitol excretion and erythrocyte galactose-1-phosphate levels are persistently elevated in patients with galactose 1-phosphate uridyltransferase deficiency. In order to determine the contribution of galactose in dietary fruits and vegetables to this phenomenon, (1) the content of galactose in a lactose-free diet was directly measured when a galactosaemic patient's diet was specifically enriched in those fruits and vegetables which contain relatively large amounts of free galactose and (2) galactitol excretion was determined during ingestion of this diet for 3 weeks and while on a synthetic diet for 1 week that provided < 8 mg galactose/day. For comparison the effect of a 3-week supplementation of 200 mg galactose/day was determined. The measured intake in total foodstuffs matched the theoretical content of galactose in the patient's diet based on amounts in fruits and vegetables alone, thus supporting the concept that fruits and vegetables are primarily responsible for galactose intake in a lactose-free diet. All of the dietary manipulations, however, had relatively little effect on metabolite levels, suggesting that endogenous galactose production is primarily responsible for the elevated levels of galactose metabolites routinely detected in patients on lactose-restricted diets. PMID- 8487508 TI - Investigating children's knowledge and understanding of AIDS. AB - Though AIDS education in schools reaches many adolescents, the incidence of adolescent HIV infection has risen dramatically. Reasons for failure to properly educate adolescents include not educating children prior to adolescence and neglecting to assess and address children's varying levels of cognitive development when designing AIDS education programs. Citing examples from a study of more than 600 elementary-age schoolchildren, this paper focuses on the importance of assessing children's understanding of disease processes rather than accepting their use of key phrases in appropriate contexts as reflecting knowledge, and using the level at which they understand disease processes rather than age as the primary determinant of students' readiness for comprehending AIDS related concepts. Guidelines for assessing how well children understand disease processes, including use of nonleading probes, are presented. PMID- 8487509 TI - Chief State School Officers rank barriers to implementing comprehensive school health education. AB - Council of Chief State School Officers (CCSSO) members were surveyed to determine their perception of barriers to implementing comprehensive school health education. CCSSO members were asked to prioritize the barriers and offer recommendations to overcome the barriers. A structured response, paired comparison survey instrument was developed and mailed to 56 of 57 CCSSO members. Eighty-two percent of the members responded. CCSSO members perceived lack of administrative commitment as the number one barrier. Lack of adequately prepared teachers and insufficient time in the school day ranked second and third, respectively. While CCSSO members offered no recommendations for overcoming the number one barrier, recommendations to overcome other barriers included high quality and more available preservice and inservice programs for teachers. PMID- 8487510 TI - School health education in the European Community. AB - The School Health Education Commission of the European Community is making efforts to improve school health education in the European Community countries. While past efforts have involved single issue causes, current activities emphasize a holistic perception of school health education. Radical education reforms throughout the European Community advocate improved health education. The movement toward quality health education in the European Community countries uses a model called the Health Promoting School, a cooperative effort involving schools, families, and communities. The model is being promoted through three stages: 1) national conferences held in each European Community country, 2) summer schools to provide teacher training, and 3) national projects, supported by the World Health Organization, agreement conducted to determine the efficacy of the Health Promoting School Model. PMID- 8487511 TI - School heart health promotion: the National Heart Foundation (Western Australian) approach. AB - The National Heart Foundation of Australia's commitment to school health promotion expanded progressively since 1983. Following establishment of health education curriculum documents by the state Ministries of Education, the Foundation targeted schoolchildren with primary prevention programs and resources. The Foundation looked beyond instructional settings to examine the influence of the school environment on the health of students and school personnel. This paper describes a school heart health promotion model implemented by the Western Australian Division of the National Heart Foundation, serving one of Australia's eight states and territories. The model incorporates elements of policy, curriculum, environment, health services, and community interaction. Though similar to comprehensive models of school health education, this model limits its application to heart health. The program operates in a nongovernment agency with unmatched potential for national reach. PMID- 8487512 TI - Incorporating health-fitness concepts in secondary physical education curricula. AB - This investigation ascertained effects of exposing high school students to classroom health-related fitness instruction involving a curriculum focused on the relationship of exercise to cardiorespiratory fitness, body composition, flexibility, strength (particularly as it relates to abdominal and lower-back muscoskeletal function), and muscular endurance. The curriculum included lectures, labs, and readings as part of the physical education course work. Ninety ninth and 10th grade students were assigned randomly to one of three physical education classes, which met daily for one, 12-week semester. Each class received the same skill-related instruction; however, the two experimental classes, in lieu of skill activities, were exposed to classroom instruction and readings dealing with health fitness topics on a one or two day per week basis. The third class of students, the control group, was engaged strictly in skill activities daily. Students exposed to health-related fitness classroom instruction displayed significantly more positive attitudes toward physical activity and a better understanding of health-related fitness than students who did not receive such information. PMID- 8487513 TI - An evaluation of a substance abuse education program for Mississippi delta pregnant adolescents. AB - A non-equivalent control group design was used to examine effectiveness of a drug and alcohol abuse prenatal care health education program for pregnant teens (N = 212) in the Mississippi delta region of southern Illinois. Experimental group posttest knowledge scores were significantly higher than control group scores; however, no significant differences occurred in attitudes between the two groups at posttest. Frequency of drug use decreased substantially for both experimental and control groups at posttest; however, significantly more experimentals than controls indicated they reduced or quit using drugs. The experimental group had a significantly lower rate of diabetes, anemia, and sexually transmitted diseases, and possibly a lower rate of spontaneous abortion depending on the statistical test used. Data suggest prenatal care health education programs may be effective methods for increasing patient awareness about the dangers of drug and alcohol abuse and may have an effect on infant and maternal outcomes. PMID- 8487514 TI - The impact of training on school professionals' knowledge, beliefs, and behaviors regarding HIV/AIDS and adolescent homosexuality. AB - The impact of training on secondary school professionals' knowledge, beliefs, and behaviors regarding HIV/AIDS and adolescent homosexuality was examined. Subjects (79 introductory and 50 advanced trainees) and 58 controls (no prior training) were systematically sampled from professionals in a statewide demonstration program to prevent HIV transmission among gay and bisexual youth. Subjects completed mailed, self-administered surveys based on the curriculum. The overall response rate was 79%. Trainees scored significantly higher than controls on knowledge pertaining to HIV and adolescent homosexuality. They also reported using greater numbers of strategies to teach students about homosexuality and to improve the mileu for homosexual students. Training at any level was independently associated with constructive behaviors, while controlling for demographic characteristics. Advanced learners were most knowledgeable and least reliant on informal sources of information. They were more likely than others to teach about homosexuality and to refer homosexual students to community services. Findings supported the hypothesized benefits of the intervention. Schools that mandate AIDS education should help staff confront the difficult issue of adolescent homosexuality. PMID- 8487515 TI - Using a student-constructed baby model to teach health subjects to learning disabled children. PMID- 8487516 TI - Hearing loss, speech, and hearing aids. AB - Modern hearing aids permit adjustment of a number of electroacoustic parameters, among them frequency response, saturation sound pressure level, and various aspects of compression. Relatively little is known, however, about how the electroacoustic characteristics of hearing aids affect the information-bearing properties of speech. Even less is known about how hearing aids might alleviate or exacerbate the effects of impaired hearing. This article reviews current knowledge in three areas: (a) characteristics of mild/moderate hearing loss, (b) information-bearing aspects of speech, and (c) the relation between electroacoustic characteristics of hearing aids and the speech signal. Concluding suggestions are made regarding the implications of the current data for selecting hearing-aid characteristics. PMID- 8487517 TI - Speech production changes under fluency-evoking conditions in nonstuttering speakers. AB - Changes in airflow and intraoral pressure between baseline and four fluency evoking conditions--choral reading (CR), metronome pacing (MET), delayed auditory feedback (DAF), and masking noise (NOISE)--were studied in 12 American English nonstuttering speakers. The duration, amplitude, and velocity of airflow and intraoral pressure development during the initial plosive and the duration and intensity of the following vowel were measured in eight target CVC words. Speech rate was computed for each sentence. Comparisons between baseline and the corresponding production in each condition revealed significant changes in peak flow, pressure rise time, peak instantaneous pressure velocity, speech rate, intensity, and vowel duration. Vowel duration increased under DAF, MET, and NOISE conditions. Peak pressure and pressure velocity decreased during CR and MET and increased during NOISE, but did not change during DAF. Subjects were consistent in the variables they modified across conditions. Changes in the aerodynamic variables were not related to intensity or rate changes. Thus, nonstuttering speakers modify intraoral pressure and flow under fluency-evoking conditions. PMID- 8487518 TI - A cepstrum-based technique for determining a harmonics-to-noise ratio in speech signals. AB - A new method to calculate a spectral harmonics-to-noise ratio (HNR) in speech signals is presented. The method involves discrimination between harmonic and noise energy in the magnitude spectrum by means of a comb-liftering operation in the cepstrum domain. Sensitivity of HNR to (a) additive noise and (b) jitter was tested with synthetic vowel-like signals, generated at 10 fundamental frequencies. All jitter and noise signals were analyzed at three window lengths in order to investigate the effect of the length of the analysis frame on the estimated HNR values. Results of a multiple linear regression analysis with noise or jitter, F0, and window length as predictors for HNR indicate a major effect of both noise and jitter on HNR, in that HNR decreases almost linearly with increasing noise levels or increasing jitter. The influence of F0 and window length on HNR is small for the jittered signals, but HNR increases considerably with increasing F0 or window length for the noise signals. We conclude that the method seems to be a valid technique for determining the amount of spectral noise, because it is almost linearly sensitive to both noise and jitter for a large part of the noise or jitter continuum. The strong negative relation between HNR and jitter illustrates that spectral noise measures cannot simply be taken as indicators of the actual amount of noise in the time signal. Instead, HNR integrates several aspects of the acoustic stability of the signal. As such, HNR may be a useful parameter in the analysis of voice quality, although it cannot be directly interpreted in terms of underlying glottal events or perceptual characteristics. PMID- 8487519 TI - Speech and swallowing function after anterior tongue and floor of mouth resection with distal flap reconstruction. AB - The purpose of this study was to assess the postoperative functioning of oral cancer patients with resections of the anterior tongue and floor of mouth, reconstructed with distal flap closure. Speech and swallowing performance was assessed for 11 men and 5 women preoperatively and at 1 and 3 months postoperatively following a standardized protocol. Speech tasks included an audio recording of a brief conversation and of a standard articulation test; swallowing function was examined using videofluoroscopy. Data were also collected on the number and duration of speech/swallowing treatment sessions, as well as the amount and duration of radiation therapy. Statistical analyses revealed that patients demonstrated a significant and severe impairment in speech and swallow functioning after surgery, with no recovery of function by 3 months post-healing. The degree of impairment in these patients may be related to the adynamic character of the distal flap used for reconstruction. Lack of improvement at the 3-month evaluation may be related to either the timing of postoperative radiation therapy or the low rate (44%) and amount of speech/swallowing treatment provided to these patients. PMID- 8487520 TI - Role of visual feedback treatment for defective /s/ sounds in patients with cleft palate. AB - The role of visual feedback in the treatment of defective /s/ sounds in patients with cleft palate is described. Six patients with cleft palate who were similar in age, velopharyngeal function, and type of misarticulation were selected for this study. Treatment was provided using either visual feedback or no visual feedback. Visual feedback for tongue placement was provided by the Rion Electropalatograph (EPG). Visual feedback for frication was provided by a multi function speech training aid (MFSTA). Improvement in /s/ sound production was assessed objectively using a method described previously (Michi et al., 1986). The results indicated that visual feedback for tongue placement and frication was especially useful in the treatment of defective /s/ sounds in patients with cleft palate who exhibited abnormal posterior tongue posturing during the production of dental or alveolar sounds. PMID- 8487521 TI - Differences between stutterers' and nonstutterers' short-term recall and recognition performance. AB - Longer rehearsal times presumably reduce the efficiency of rehearsal and, hence, of short-term recall. The present experiment examined the question as to whether the slower subvocalization rate of people who stutter is correlated with inferior short-term serial recall and recognition performance. Rate of overt articulation was taken as a measure of rehearsal time. Lists of four nonlexical CVC syllables were presented for short-term serial recall and for short-term recognition. Nineteen adults who stutter and 30 nonstutterers participated in the experiment. In the serial reproduction task the subjects who stuttered reproduced significantly fewer items correctly than did nonstutterers. Recognition performance was measured by nonparametric measures of sensitivity and bias as defined in signal detection theory. The stuttering subjects had a significantly lower sensitivity resulting primarily from a higher false alarm rate. Rate of overt articulation was significantly related to one measure of short-term recall but not to the sensitivity of recognition. These results were interpreted as suggesting that people who stutter have slower phonological encoding and rehearsal times, that they make less use of nonphonological forms of coding than do nonstutterers, and that within their phonological system, activation more easily spills over to similar items. PMID- 8487522 TI - Speech breathing in Parkinson's disease. AB - Breathing was investigated in 14 male subjects with Parkinson's disease and 14 healthy male control subjects. Kinematic, spirometric, acoustic, and pressure data were used to assess function during resting tidal breathing, reading aloud, and monologue production. Data were collected at two times during the drug cycle for subjects with Parkinson's disease. During resting tidal breathing, subjects with Parkinson's disease, on average, had a faster breathing rate, greater minute ventilation, and smaller relative contribution of the rib cage to lung volume change than did healthy control subjects. During speech breathing, rib cage volume was smaller and abdominal volume was larger at initiation of the breath groups for subjects with Parkinson's disease than for healthy control subjects. Subjects with Parkinson's disease produced fewer words and spent less time producing speech per breath group and tended to have a faster interpause speech rate than did healthy control subjects. There was no difference between groups for duration of inspirations between speech breath groups. Oral pressure was lower for subjects with Parkinson's disease but estimated tracheal pressure did not differ between the two subject groups. Few differences were found between the two times in the drug cycle for resting and speech breathing. Results provide indirect evidence for reduced relative compliance of the rib cage to the abdomen for subjects with Parkinson's disease as compared to healthy control subjects. In addition, the results support the possibility of inadequate valving of the air stream for subjects with Parkinson's disease. PMID- 8487523 TI - Communication behaviors of infants with hearing loss and their hearing mothers. AB - This study documented communication behaviors of hearing mothers and infants with a hearing loss that had been identified before 9 months of age (Group HL). Their behaviors were compared with those of mothers and infants without hearing loss (Group H). Each group was composed of 18 dyads videotaped during mother-infant play with toys at 12- and 18-months. Group HL mothers produced more gestural and tactile communications (but similar numbers of vocal communications) compared to H mothers. In contrast with earlier reports, infants with and without hearing loss were similar in quantity of gestural and vocal expressive prelinguistic communication behaviors. Despite group similarities in quantity of prelinguistic communications, H infants as a group surpassed HL infants in expression of formal language by 18 months. There was considerable variation within each group in formal language expression, however, with performance of some HL infants matching that of H infants. PMID- 8487524 TI - Access behaviors of children with specific language impairment. AB - The verbal and nonverbal behaviors used by 5 children with specific language impairment (SLI) to attempt to gain access into established interactions were described and compared with those of chronological-age-mates and language-similar control subjects. Three of the children with SLI were unsuccessful. Two of the children with SLI achieved access but did so without using linguistic forms like those most normal-language children use. All of the children with normal language accessed, and most did so quickly and easily using an orderly and sequential set of indirect behaviors. The findings contribute to social-linguistic characterizations of SLI and clarify specific aspects of access described in the normal-language literature. PMID- 8487525 TI - A system for quantifying the informativeness and efficiency of the connected speech of adults with aphasia. AB - A standardized rule-based scoring system, the Correct Information Unit (CIU) analysis, was used to evaluate the informativeness and efficiency of the connected speech of 20 non-brain-damaged adults and 20 adults with aphasia in response to 10 elicitation stimuli. The interjudge reliability of the scoring system proved to be high, as did the session-to-session stability of performance on measures. There was a significant difference between the non-brain-damaged and aphasic speakers on each of the five measures derived from CIU and word counts. However, the three calculated measures (words per minute, percent CIUs, and CIUs per minute) more dependably separated aphasic from non-brain-damaged speakers on an individual basis than the two counts (number of words and number of CIUs). PMID- 8487526 TI - Temporal analysis in children. AB - This study investigated the development of temporal resolution as a function of frequency region using a modified masking period pattern paradigm. This paradigm also allowed age-dependent comparisons of within-channel (temporal resolution) versus across-channel (comodulation masking release [CMR]) processing of temporal information to be made in the same listeners. The results indicated that temporal resolution improves with age. At low frequencies, this improvement continues beyond 10 years of age, whereas at high frequencies performance approaches adult levels by about age 6. Although it is reasonable to expect an association between CMR and temporal acuity, the measure of CMR did not show a significant age effect. The possibility was raised that the poorer temporal resolution of children may not reflect simply a deficiency in peripheral processing of temporal information. PMID- 8487527 TI - Loudness matching of signals spectrally shaped by a simulated hearing aid. AB - A hearing aid with multiple frequency responses was simulated by programming an equalizer to produce spectral tilt factors of -6, 0, and +6 dB/octave over the frequency range from 0.25 kHz to 4 kHz. Listeners with normal hearing matched the loudness of signals (speech and white noise) that were shaped by these different equalizer settings and delivered via an insert earphone. All signals with spectra that were tilted, either negatively or positively, were perceived as louder than untilted signals. The general pattern of loudness matching was similar across subjects, and intrasubject judgments were found to be highly transitive. A measure of signal power was found to account only moderately well for the individual data. Preliminary evidence from a follow-up study using tilt factors less severe than those used in the main experiment suggests that loudness differences are roughly proportional to the degree of spectral tilt. The incorporation of level corrections approximating those necessary to achieve equal loudness is recommended in the fitting of programmable hearing aids. PMID- 8487528 TI - Temporary threshold shift caused by hearing aid use. AB - Temporary threshold shift (TTS) over a wide range of frequencies was found after 4 hours of hearing aid use by a 15-year-old student with severe sensorineural hearing loss who was using real-ear insertion gains 10 to 20 dB greater than those recommended by the current National Acoustic Laboratories (NAL) procedure for selecting the gain and frequency response of hearing aids. Measurements were made of her noise exposure during hearing aid use with a noise dosimeter. The real-ear insertion response and input-output function of her hearing aid were measured with a real-ear gain analyzer and were used to calculate in-ear noise levels from the noise levels measured by the dosimeter. The amount of TTS could be predicted from the in-ear noise levels and the student's hearing levels (HLs) by means of a mathematical model consisting of the Modified Power Law (MPL) of Humes and Jesteadt (1991) combined with equations for predicting TTS in listeners with normal hearing published by Mills, Gilbert, and Adkins (1979). The mean of the instantaneous A-weighted in-ear noise levels proved to be the appropriate equivalent continuous level (ECL) for use in the predictions. The MPL was also used to determine safety limits for TTS due to hearing aid use. The observed TTS exceeded the safety limits at all frequencies up to and including 2000 Hz. It was therefore considered desirable for the girl to use less gain at frequencies from 500 to 1500 Hz. PMID- 8487529 TI - Importance of patient and processor variables in determining outcomes with cochlear implants. AB - Within-subjects comparisons of processing strategies for cochlear implants are reviewed. Compressed analog strategies were compared to interleaved pulses strategies in tests with one group of 8 subjects, and to continuous interleaved sampling strategies in tests with another group of 11 subjects. The tests included open-set recognition of words and sentences. The results show that, while different strategies may produce quite different outcomes across subjects, individual performances with one processing strategy are significantly correlated with those of alternative strategies. These findings emphasize the importance of patient variables in determining outcomes across a variety of prosthesis designs. PMID- 8487530 TI - Auditory processing in children's speech perception: results of selective adaptation and discrimination tasks. AB - Five- to six-year-old children and adults participated in discrimination and selective adaptation speech perception tasks using a synthetic consonant-vowel continuum ranging from [ba] to [da]. In one condition of selective adaptation, attention was focused on the adapting stimulus, the continuum-endpoint [ba], with a whispering task. In another condition, attention was focused away from the continuum-endpoint [da] adaptor to contralaterally presented syllables "SHE" and "SEE." Results, compared with two more typical adaptation conditions, indicated that focused attention did not augment selective adaptation effects, particularly for children who showed smaller effects with focused attention on the adaptor. In contrast to adults, children did not significantly change labeling responses after exposure to endpoint-[ba] adaptors, results matching those of Sussman and Carney (1989). However, children did significantly change labeling following exposure to endpoint-[da] adaptors. Discrimination findings with five-formant consonant-vowel and single-formant stimuli supported the importance of acoustic processing for the selective adaptation tasks performed. Together, results support hypotheses of sensory processing differences in younger, normally developing children compared with adults and show that such abilities appear to be related to speech perception skills. PMID- 8487531 TI - Influence of frequency selectivity on comodulation masking release in normal hearing listeners. AB - Experiments 1 and 2 investigated the effect of frequency selectivity on comodulation masking release (CMR) in normal-hearing subjects, examining conditions where frequency selectivity was relatively good (low masker level at both low [500-Hz] and high [2500-Hz] signal frequency, and high masker level at low signal frequency) and where frequency selectivity was somewhat degraded (high masker level and high signal frequency). The first experiment investigated CMR in conditions where a narrow modulated noise band was centered on the signal frequency, and a wider comodulated noise band was located below the band centered on the signal frequency. Signal frequencies were 500 and 2000 Hz. The masker level and the frequency separation between the on-signal and comodulated flanking band were varied. In addition to conditions where the flanking band and on-signal band were presented at the same spectrum level, conditions were included where the spectrum level of the flanking band was 10-dB higher than that of the on signal band, in order to accentuate effects of reduced frequency selectivity. Results indicated that CMR was reduced at the 2000-Hz region when masker level was high, when the frequency separation between on-signal and flanking band was small, and when a 10-dB level disparity existed between the on-signal and flanking band. In the second experiment, CMR was investigated for narrow comodulated noise bands, presented either without any additional sound or in the presence of a random noise background. CMR increased slightly as the masker level increased, except at 2500 Hz when the noise background was present. The decrease in CMR at 2500 Hz with the high masker level and with a noise background present could be explained in terms of reduced frequency selectivity. In a third experiment, we compared performance for equal absolute bandwidth maskers at a low (500-Hz) and a high (2000-Hz) stimulus frequency. Results here suggested that detection in modulated noise may be reduced due to a reduction in the number of quasi-independent auditory filters contributing temporal envelope information. The effects found in the present study using normal-hearing listeners under conditions of degraded frequency selectivity may be useful in understanding part of the reduction of CMR that occurs in cochlear-impaired listeners having reduced frequency selectivity. PMID- 8487532 TI - Tracking of "moving" fused auditory images by children. AB - Recent investigations (Cranford, Boose, & Moore, 1990a,b; Moore, Cranford, & Rahn, 1990) studied the ability of normal adult subjects to localize sounds under conditions that elicit the Precedence Effect. In different tests, subjects were required either to report the perceived location of a stationary fused auditory image (FAI) or track the apparent motion of a "moving" FAI. Movement of the FAI was simulated by incrementally varying the delay between pairs of clicks presented, one each, from two matched loudspeakers placed on opposite sides of the listener. In the present study, groups of normally developing children, ranging in age from 6 to 12 years of age, were tested with these two procedures. Although subjects performed at normal adult levels with the stationary FAI test, a significant age-related trend was observed with the moving FAI test. The younger children exhibited poorer tracking performances than did the older children. These results provide evidence that significant changes in binaural temporal processing abilities may occur in the early childhood years. PMID- 8487533 TI - Benefit from visual cues in auditory-visual speech recognition by middle-aged and elderly persons. AB - The benefit derived from visual cues in auditory-visual speech recognition and patterns of auditory and visual consonant confusions were compared for 20 middle aged and 20 elderly men who were moderately to severely hearing impaired. Consonant-vowel nonsense syllables and CID sentences were presented to the subjects under auditory-only, visual-only, and auditory-visual test conditions. Benefit was defined as the difference between the scores in the auditory-only and auditory-visual conditions. The results revealed that the middle-aged and elderly subjects obtained similar benefit from visual cues in auditory-visual speech recognition. Further, patterns of consonant confusions were similar for the two groups. PMID- 8487534 TI - Influences of age and hearing loss on the precedence effect in sound localization. AB - Cranford, Boose, & Moore (1990a) reported that many elderly persons exhibit problems in perceiving the apparent location of fused auditory images in a sound localization task involving the Precedence Effect (PE). In the earlier study, differences in peripheral hearing sensitivity between young and elderly subjects were not controlled. In the present study, four groups of young and elderly subjects, matched with respect to age and the presence or absence of sensorineural hearing loss, were examined to determine the effects of these two factors on performance with the PE task. Although significantly poorer performances on the PE task were found to be associated with both increased age and hearing loss, additional tentative evidence was obtained that the presence of hearing loss may have a relatively greater detrimental effect on the performance of at least some elderly subjects than it does on younger persons. PMID- 8487535 TI - Auditory detection of the human brainstem auditory evoked response. AB - The human brainstem auditory evoked response (BAER) is a far-field electrical potential recorded from the scalp in response to transient acoustic stimuli. Typically, voltage measurements are obtained for a period of about 10 msec following the acoustic stimulus, which is repeated and summed several hundred or thousand times to permit extraction of the response from ongoing nonauditory neural activity. The judgment about whether a response has been obtained is normally based on the pattern observed in a visual display of the waveform. In this study, we investigated whether listeners can distinguish BAERs elicited by acoustic clicks from control waveforms obtained with no acoustic stimulus when the waveforms were presented auditorily. For this purpose, BAER and control waveforms were transduced by an earphone and used in an auditory detection task. Several presentation strategies were examined, including lengthening the waveform by playing it at a lower sampling rate, playing the waveform repetitively, and using the waveform to frequency modulate a pure-tone carrier. The results indicated that the BAER, when extended in duration and used to frequency modulate a 1000-Hz pure tone, was highly detectable in a YES-NO paradigm for BAERs elicited with high-level (e.g., 70 dB re. behavioral detection threshold) acoustic clicks. Performance declined to near chance as the level of the BAER eliciting stimulus was lowered to 10 dB. In general, detection performance for stimuli presented visually was slightly, but consistently, superior to that which occurred for stimuli presented auditorily. PMID- 8487536 TI - The prevention of prenatal alcohol use: a critical analysis of intervention studies. AB - Alcohol is a major cause of birth defects and mental retardation in the U.S. The yearly cost to care for those affected has been estimated to be over $300 million. Prenatal education and counseling have been advocated as techniques to reduce alcohol use in pregnancy. The purpose of this study was to critically review investigations that used these methods in order to determine their effectiveness. Reports of relevant studies were found by searching Medline, the ETOH database and bibliographies of primary sources. Only five studies were identified that met predetermined selection criteria. As judged by usual methodologic standards for intervention programs, only one was of acceptable quality. None employed a randomized design, and only two compared the treatment group to a control group. Both these studies found no difference in alcohol use between control and intervention groups. An ethical argument was used by several authors to justify performing inadequately controlled studies. Since no intervention has proven to be superior to the usual care delivered to pregnant women, this problem can be overcome through the use of controls who receive this level of care. Despite the public health importance of prenatal alcohol use, interventions to alter this behavior have not been rigorously evaluated, and the benefits of any specific approach are unclear. Randomized trials are ethically justified and guidelines for undertaking such studies are proposed. PMID- 8487537 TI - Spirituality and purpose in life in alcoholism recovery. AB - This study examines the relationship between spirituality and recovery from alcoholism. Spirituality was defined as the extent of practice of Alcoholics Anonymous Steps 11 and 12 and was measured by a Step Questionnaire developed by the researcher. Step 11 suggests prayer and meditation and Step 12 suggests assistance of other alcoholics. Expressed degree of purpose in life was also seen as a reflection of spirituality. It was postulated that the extent to which Steps 11 and 12 were practiced would be positively correlated with the extent of purpose in life reported by 100 Alcoholics Anonymous members. The major findings of this study are significant positive correlations between practice of Step 11 and purpose in life scores (r = .59, p < .001) and between Step 11 and length of sobriety (r = .25, p < .01). Number of Alcoholics Anonymous meetings attended was significantly correlated with purpose in life scores (r = .24, p < .01) and length of sobriety (r = .25, p < .01). These findings suggest that a sense of purpose in life increases with continuing sobriety and practice of the spiritual principles of Alcoholics Anonymous. PMID- 8487538 TI - The external costs of alcohol abuse. AB - This study reviews the economic concepts of external and private costs and interprets them in the context of alcohol abuse. Previous economic cost studies by NIAAA are found inadequate in that they fail to differentiate between external and private costs. This study differentiates between external and private costs. This study finds that the external costs of alcohol abuse in 1985 were $9.5 billion with an additional $4.5 billion in government incurred costs. Policy implications of this finding are discussed. PMID- 8487539 TI - Prediction of alcohol-related casualties in the emergency room: a U.S.-Spain comparison. AB - Alcohol consumption variables predictive of casualties are compared in probability samples of emergency room (ER) patients in two countries with different drinking patterns; (1) Spain, where frequent light drinking is the typical pattern (N = 2,072), and (2) the U.S. (i.e., California), where less frequent heavier drinking is more typical (N = 1,756). Logistic regression was used to evaluate the predictive value of breath-analyzer readings, drinking patterns and problems, time and place of injury, and demographic characteristics on ER admission for injuries vs noninjuries and for alcohol-related injuries vs non-alcohol-related injuries. Quantity and frequency of drinking, time and place of injury, and feeling drunk at the time of the event were predictive of casualties in California. Drinking patterns were less predictive of injury occurrence and of alcohol-related injury in Spain. One possible explanation for this difference may be that drinking is integrated into society as part of the wine drinking culture in Spain, while in the U.S. drinking occasions are more circumscribed by appropriateness of time and place. PMID- 8487540 TI - Perception of male drinkers as a function of their alcoholic beverage preference. AB - The present study examined perception of a man's likelihood of driving after drinking and his ability to do so as a function of his choice of beverage. Perceptions of his social characteristics were also examined. The sample was composed of 200 volunteer undergraduate psychology students. Equal numbers of male and female subjects read one of four vignettes which varied only in the male protagonist's choice of beverage: beer, wine, shots of distilled spirits, or cola. After reading the story, subjects answered multiple-choice questions about the character, tapping social judgments, situational judgments and drinking and driving judgments. Subject drinking habits were also assessed. The most notable result was the consistently positive perception of the protagonist portrayed as an abstainer. The lack of a consistent alcoholic beverage distinction implies that the beer-spirits double standard is far from a clear-cut discrimination. Possible explanations for results are discussed. This study questions the robustness of the alcoholic beverage type bias and reflects the need for future research. PMID- 8487541 TI - Alcohol availability, drinking contexts and drinking problems: the Iowa experience. AB - Before/after survey data were used to investigate the effects that a wine and spirits privatization-induced increase in alcohol availability might have had on drinking contexts and, in turn, what effect any context changes might have had on specific drinking-related troubles. State surveys representing the aged 18+ noninstitutionalized population of Iowa were conducted in 1985, prior to the wine privatization; in 1986, after the wine privatization but before the spirits privatization; and in 1989, after both wine and spirits sales had been privatized. Despite substantial increases in the number of off-premise outlets for bottled wine and spirits following their privatizations, there was little or no change in the frequency of drinking in several different contexts or in the specific kinds of drinking-related problems studied. PMID- 8487542 TI - The stress and negative affect model of adolescent alcohol use and the moderating effects of behavioral undercontrol. AB - Empirical evidence for the stress and negative affect model of adolescent alcohol use has been inconsistent. We hypothesized that this inconsistent support was partially due to a third variable that moderates the model's effects. The current study assessed behavioral undercontrol as a moderator of the stress and negative affect model of adolescent alcohol use. Using a community-based sample of adolescent children of alcoholics (COAs) and a demographically matched comparison group (non-COAs), life stress, negative affect, behavioral undercontrol and alcohol use were assessed. Results showed that the stress and negative affect model predicted alcohol use. Consistent with theoretical predictions and previous research, negative affect partially mediated the relation between stress and alcohol use. However, behavioral undercontrol did not moderate the effects of stress and negative affect for COAs and non-COAs. Theoretical and methodological implications of the findings are discussed. PMID- 8487543 TI - Validity and reliability of self-reported drinking behavior: dealing with the problem of response bias. AB - This work assesses the validity and reliability of self-reported survey data on drinking behavior. There is evidence to suggest that data are adversely affected by bias from underreporting. This bias affects the validity of measures of consumption of alcohol and can have deleterious effects on the results of some forms of statistical estimation. Data for this study were collected at an isolated military base. The remoteness of this site and the fact that it is a military station made it possible to estimate the actual level of consumption of alcohol for the population by assessing apparent consumption through officially recorded sales of alcohol. The results of eight measures of consumption of alcohol were compared with apparent consumption, as established by documented sales, and the validity and reliability of the various measures were determined using the classical correlational approach. The validity and reliability of the data generated by the self-report survey were also analyzed using LISREL, the measurement model in particular. The results indicate that various instruments used to assess the consumption of alcohol produce very different outcomes in terms of their validity and reliability, some questions being considerably more valid and reliable than others. Two of the more salient characteristics of questions that affect validity and reliability were isolated, namely a question's ability to aid recall and its ability to mitigate the effects of persons providing socially desirable responses. The LISREL results show that these are two underlying factors for the measurement of the consumption of alcohol. It is concluded that questions that produce valid and reliable responses do so for identifiable reasons, and measurement instruments can be improved by incorporating particular features. PMID- 8487544 TI - Assessment of prepubertal and postpubertal boys and girls at risk for developing alcoholism with P300 from a visual discrimination task. AB - A total of 86 children (45 male) between the ages of 8-18 who were from families that were either at high- or low-risk for developing alcoholism were evaluated in a visual event-related potential paradigm. The children responded to two target conditions (hard and easy) and a blank condition by pressing an appropriate button. P300 amplitude was reduced in prepubescent boys who were at high-risk for developing alcoholism. Reaction time data for type of target indicated that, while latency was longer for the hard condition compared to the easy one, no significant differences by risk status were found. Performance accuracy did not differ by group status. These behavioral findings suggest that P300 amplitude is an electrophysiological marker of alcoholism risk in young boys. PMID- 8487545 TI - Reactivity to alcohol-related cues in heavy and light drinkers. AB - Physiological responses and self-reported desire for alcohol were compared in heavy (n = 21) and light (n = 29) drinkers under each of two cue conditions. The cues were presented in a counterbalanced order and consisted of the sight, smell and taste of the subject's preferred alcoholic beverage (alcohol cue) and of a nonalcoholic lemon-flavored drink (neutral cue). Heavy drinkers showed a significant linear increase in reported desire for alcohol over time in the presence of the alcohol cue. This persistent increase in desire for alcohol seen in heavy drinkers contrasted with the initial increase shown by light drinkers which dissipated over time. Neither group showed any significant change in desire for alcohol when presented with the neutral cue. Heavy drinkers showed lower levels of skin conductance than light drinkers and all subjects showed changes in heart rate during exposure to both cues. Heart rate was affected differentially in the two groups of drinkers but only when the alcohol cue was presented first. Neither blood pressure nor stress and arousal levels changed significantly from pre- to post-cue presentations. The findings of this study have implications for understanding the nature and time course of cue-elicited desire for alcohol and its potential role in the development and treatment of alcohol dependence. PMID- 8487546 TI - Acute effects of alcohol on regional cerebral blood flow in man. AB - Acute effects of alcohol in a low (0.7 g/kg) and a high dose (1.5 g/kg) on regional cerebral blood flow (rCBF) were measured with 133Xe inhalation technique at resting conditions in 13 normals. Mean hemisphere CBF increased globally by 12% at the lower dose and 16% at the higher dose. A normal hyperfrontal flow pattern was seen in both alcohol conditions. There were, however, significant regional differences in response to alcohol. The largest rCBF increase was observed in prefrontal regions at the lower dose, and in temporal regions at the higher. Expressed in relative values (% of the whole brain CBF), the temporal rCBF increased linearly with increasing alcohol dosage, while the prefrontal rCBF showed a increase at the lower dose followed by a decrease at the higher dose. It is concluded that alcohol has two types of acute effects on rCBF, a global vasodilatory effect and some regional effects, most clearly seen in prefrontal and temporal regions. The prefrontal flow augmentation following acute alcohol intake may be related to a transient arousal reaction, which has been reported by others. The temporal flow increase may be related to effects of alcohol on emotions and mood. PMID- 8487547 TI - Frontiers in HIV pathogenesis. March 29-April 4, 1993, Albuquerque, New Mexico. 22nd annual Keystone symposia. Abstracts. PMID- 8487548 TI - Progress in basic research of wound repair and its application to clinical management of problematic wounds. 22nd annual Keystone symposia. March 29-April 4, 1993, Breckenridge, Colorado. Abstracts. PMID- 8487549 TI - Extracellular matrix in development and disease. 22nd annual Keystone symposia. March 29-April 4, 1993. Breckenridge, Colorado. Abstracts. PMID- 8487550 TI - Genetically targeted research and therapeutics: antisense and gene therapy. 22nd annual Keystone symposia. April 12-18, 1993, Keystone, Colorado. Abstracts. PMID- 8487551 TI - Gene therapy. 22nd annual Keystone symposia. April 12-18, 1993, Keystone, Colorado. Abstracts. PMID- 8487552 TI - B and T cell lymphomas. 22nd annual Keystone symposia. April 17-23, 1993, Copper Mountain, Colorado. Abstracts. PMID- 8487553 TI - Bacterial chromosomes. 22nd annual Keystone symposia. April 18-25, 1993, Keystone, Colorado. Abstracts. PMID- 8487554 TI - HIV pathogenesis in infants and children. 22nd annual Keystone symposia. March 29 April 2, 1993, Albuquerque, New Mexico. Abstracts. PMID- 8487555 TI - In memoriam Nina S. Braunwald (1928-1992). PMID- 8487556 TI - Time course of dimension and function of the autologous pulmonary root in the aortic position. AB - Although the autologous, fully vital, and compatible pulmonary root theoretically offers the prospect of an ideal aortic valve substitute, this type of replacement is performed in only a few centers. Major concern relates to the fate of root dimension and function in the systemic circulation and is largely unknown. To investigate the fate of the aortic root, we conducted echocardiographic examinations of eight freestanding pulmonary roots used for aortic valve replacement in adults. The studies were performed at discharge from the hospital and up to 21 months (mean 12.5 +/- 6.6 months) after the operation, as well as in 26 matched control subjects. There were no significant differences between the first and second postoperative studies regarding the root diameter (mean 26.6 +/- 2.1 mm and 27.6 +/- 2.6 mm, respectively), which was within control limits, the maximum transvalvular pressure gradient (mean 4.6 +/- 1.2 mm Hg and 6.6 +/- 2.1 mm Hg, respectively), the maximum leaflet separation (mean 22.1 +/- 1.4 mm and 22.1 +/- 1.8 mm, respectively), and the degree of insufficiency. At the first study, grade I aortic regurgitation was found in four patients and grade I-II in one patient. Regurgitation increased slightly in one patient with an abnormal leaflet. In three patients primary grade I regurgitation disappeared. These data suggest that the pulmonary root in the aortic position can withstand systemic circulation without changes in dimension and function for up to 21 months. Furthermore, some evidence is provided to indicate that in certain cases the viable autograft may adapt to systemic pressure, as indicated by the disappearance of primary regurgitation. PMID- 8487557 TI - Surgical repair of type A aortic dissection by the circulatory arrest-graft inclusion technique in sixty-six patients. AB - During an 8-year period (1984 to 1991) 66 patients (mean age 59 years, range 26 to 84 years) with type A aortic dissection (60 ascending aorta tears, 6 arch tears; 35 acute, 31 chronic) had surgical repair by a continuous suture-graft inclusion technique. Hypothermic circulatory arrest (16 degrees C) was used in 58 patients (35/35 acute, 23/31 chronic; mean arrest time 26 minutes, range 10 to 55 minutes). Fifty-two patients had hemiarch repair and 6 had total arch replacement. Aortic valve disease necessitated treatment in 38 patients (1 valved conduit, 20 valve replacements, 17 valve repairs). Recently 11 patients had valve repair by reconstruction of the native aortic root, by means of techniques similar to those used for homograft valve insertion. Operative mortality was 9% (14% acute, 3% chronic). Stroke occurred in 2 patients (3%) and was fatal in both. Variables suggestive of increased operative risk by univariate analysis were acuteness (p = 0.12), visceral ischemia (p = 0.12), and preoperative shock (p = 0.13). No variable was significant by multivariate analysis. Overall actuarial survival at 48 months was 77%, with 3 late deaths from a ruptured distal aneurysm. Late computed tomography or magnetic resonance imaging scan was done in 28 patients at a mean interval of 33 months. These studies identified 1 patient with a pseudoaneurysm requiring reoperation and 3 patients with contained flow between the graft and the wrap. Three patients required late operation: 1 for pseudoaneurysm, 1 for arch dissection, and 1 for repair of a distal aneurysm. PMID- 8487558 TI - Very small-diameter polyurethane vascular prostheses with rapid endothelialization for coronary artery bypass grafting. AB - Two types of spongy polyurethane-polydimethylsiloxane blend (Cardiothane 51, Kontron Instruments, Inc., Everett, Mass.) vascular grafts with an internal diameter of 1.5 mm were fabricated by a spray, phase-inversion technique. Low porosity grafts with hydraulic permeability of 2.7 +/- 0.4 ml/min per square centimeter and medium-porosity grafts with hydraulic permeability of 39 +/- 8 ml/min per square centimeter displayed good handling properties and suturability. Twelve straight low-porosity grafts, 17 straight medium-porosity grafts (1.5 to 2.0 cm in length), and one loop medium-porosity graft (10 cm in length) were implanted by the same surgeon end to end in the infrarenal aorta of 30 male Sprague-Dawley rats. Three months after implantation, patency was 8% for low porosity grafts (1/12) and 76% for straight medium-porosity grafts (13/17). The loop medium-porosity graft was also patent. The sole patent low-porosity graft showed neointimal hyperplasia and incomplete endothelialization. All but one of the patent straight medium-porosity grafts showed a glistening and transparent neointima with complete endothelialization and no anastomotic hyperplasia. The loop medium-porosity graft displayed endothelialization from each anastomosis and in many islands in the middle portion of the graft, totalling 47% of the luminal surface by morphometric analysis. Thick mural thrombus, anastomotic hyperplasia, or aneurysm formation were not observed in any patent medium-porosity graft. These data indicate that in the rat aortic replacement model it is possible to achieve patency and a high degree of endothelialization in very small-diameter prostheses of appropriate porosity. PMID- 8487559 TI - Acceleration of neointima formation in vascular prostheses by transplantation of autologous venous tissue fragments. Application to small-diameter grafts. AB - We have previously demonstrated rapid and complete endothelialization in synthetic fabric vascular prostheses that have been pretreated with autologous venous tissue fragments. However, significant thrombogenicity has been a major problem when this method has been applied to small-diameter grafts. By masking the positively charged collagen fibrils in the tissue fragments with negatively charged heparin, we were able to overcome this problem. A canine jugular vein was resected, minced into tissue fragments, and suspended. This mixture was sieved through the wall of a highly porous vascular prosthesis with a water porosity value of 4,000 ml/cm2 per minute by pressurized injection, which caused the tissue fragments to be trapped in the graft wall. Tissue-fragmented grafts (7 mm inside diameter, 5.7 cm long) were implanted into the thoracic aorta of 35 dogs. In addition, tissue-fragmented grafts of small diameter (4 mm inside diameter, 3.5 cm long) were pretreated with heparin and implanted into the carotid arteries of 16 dogs (32 grafts). Preclotted grafts without tissue fragmentation were implanted into the thoracic aorta (25 dogs) and carotid arteries (6 dogs, 12 grafts) as controls. Grafts were explanted from 1 to 495 days after implantation. New arterial wall formation was complete throughout the tissue-fragmented grafts within 2 weeks; however, in the control grafts, neointima formation was limited to the anastomotic sites even after 2 months. Twenty small-caliber tissue fragmented grafts that were pretreated with heparin in the carotid position were patent, but all the control grafts were occluded within 1 week. These results demonstrate that neointima formation can be enhanced in synthetic fabric prostheses; furthermore, long-term patency of vascular grafts of small caliber is possible in dogs with this tissue-fragmentation technique. PMID- 8487560 TI - Bless the babies: one hundred fifteen late survivors of heart transplantation during the first year of life. The Loma Linda University Pediatric Heart Transplant Group. AB - There is a rapid growth of interest in heart transplantation therapy during early infancy. From 10% to 25% of the infants who are listed for transplantation annually have died while awaiting a donor heart. There has been no significant trend in this variable. Since November 1985, 140 consecutive orthotopic transplantation procedures were performed in 139 infants who were from 3 hours to 12 months of age. Indications for transplantation included hypoplastic left heart syndrome (63%), other complex structural anomalies (29%), myopathy (6.5%), and tumors (1.5%). Most recipients had ductus-dependent circulation and received continuous infusion of prostaglandin E1. Heart donors were usually victims of trauma, sudden infant death, or birth asphyxia. A donor-recipient weight ratio of 4.0 or less was found to be acceptable. The amount of time the graft underwent cold ischemia, ranged from 64 to 576 minutes. The procurement process was facilitated by a single dose of cold crystalloid cardioplegic solution and cold immersion transport. Profound hypothermic circulatory arrest was used for graft implantation. One hundred twenty-four (89%) recipients survived transplantation and were discharged from the hospital. There were 9 late deaths, which resulted in an 83% overall survival. The 5-year actuarial survival is 80%. The survival among newborn recipients (n = 60) at 5 years is 84%. Chronic immunomodulation was cyclosporine-based and steroid-free. Surveillance was noninvasive and relied heavily on echocardiography, electrocardiography, and clinical intuition. There was one documented late lethal infection, tumor was not encountered, and coronary occlusive disease was known to exist in only one long-term survivor. We concluded that transplantation results in excellent life quality and is a highly effective and durable therapy when applied during early infancy. PMID- 8487561 TI - Inhibition of platelet function by heparin. An etiologic factor in postbypass hemorrhage. AB - The effect of heparin (5 U/ml) on platelet function was examined by hemostatometry in vitro. A wide individual variation of this effect was found in 290 patients who underwent cardiac operations: 8.6% (25) experienced a proaggregatory effect, 58.6% (170) experienced a mild to moderate inhibition of platelet function, and 32.8% (95) experienced a severe inhibition. No significant difference was found among patient characteristics, including antiplatelet medication, in these three subgroups. In vitro measurements correlated significantly with ex vivo measurements, that is, from blood taken after heparinization (p < 0.0001; r = 0.97, n = 15). In 111 patients who underwent cardiac surgical intervention, a significant correlation (p < 0.0001; 0.4 < r < 0.52) was found between preoperative measurements of the degree of inhibition of platelet function by heparin and the total postoperative blood loss after 4, 12, and 18 hours. Similarly, there was a significant difference (p < 0.0001) in the total blood loss at 4, 12, and 18 hours between the subgroups that showed, in vitro, a mild to moderate inhibition of platelet function preoperatively compared with a severe inhibition (713 +/- 43 ml versus 1172 +/- 76 ml at 18 hours). It is concluded that platelet inhibition as a result of heparin varies among patients and appears to be a previously unrecognized etiologic factor in bleeding after cardiopulmonary bypass. PMID- 8487562 TI - Ventricular function after normothermic versus hypothermic cardioplegia. AB - Warm cardioplegia produced by essentially continuous infusion has been used as an alternative to traditional cold intermittent infusion techniques during cardiac surgery, but its effects on postoperative left ventricular function have not been defined. We performed a randomized clinical trial to assess the effects of warm and cold blood cardioplegia on load-independent indices of ventricular function. Fifty-three patients were randomized to warm (n = 27) or cold (n = 26) cardioplegia. Myocardial oxygen consumption, lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during cardioplegia and reperfusion. In 13 patients per group, pressure-volume loops were constructed and ventricular function was assessed 3 hours after the operation. Warm cardioplegia resulted in greater myocardial lactate production but improved recovery of oxygen consumption during reperfusion. Depletion of adenosine triphosphate was similar between groups, but total adenine nucleotides (adenosine triphosphate + adenosine diphosphate + adenosine monophosphate) fell further during warm cardioplegia. Cold cardioplegia was associated with an accumulation of adenosine diphosphate and adenosine monophosphate. Creatine kinase MB isoenzyme release was reduced in the warm group. Three hours after the operation, end-systolic elastance and preload-recruitable stroke work index were increased after warm cardioplegia, and early diastolic relaxation was also increased. Increased systolic function after warm cardioplegia may have been related to improved myocardial protection, elevated arterial lactate concentrations, or increased circulating catecholamine levels. Altered diastolic compliance in the warm group may reflect greater active relaxation during early diastolic filling. PMID- 8487563 TI - The microvascular distribution of cardioplegic solution in the piglet heart. Retrograde versus antegrade delivery. AB - The uniform distribution of cardioplegic solution to all areas of the microvasculature is considered critical for myocardial protection. Despite this, little information exists regarding the ability of retrogradely infused cardioplegic solution to perfuse the microvasculature of the heart. In this report, the microvascular distribution of retrogradely delivered cardioplegic solution was studied by means of a technique to quantitatively demonstrate capillary perfusion. Duroc piglet hearts were subjected to either antegrade (n = 4) or retrograde (n = 8) perfusion fixation with 2.5% glutaraldehyde and subsequently perfused with NTB-2 (an intracapillary marker). The results indicate that retrogradely delivered NTB-2 consistently perfused the anterior half of the intraventricular septum and the anterior and lateral free walls of the left ventricle but inconsistently perfused the posterior half of the intraventricular septum, the posterior wall of the left ventricle, and a small paraseptal region of the right ventricle. The remainder of the right ventricle was not perfused. In contradistinction, all regions of the heart were consistently perfused by the antegrade technique. In regions of the heart in which retrograde microvascular perfusion occurred, no statistical difference was found in the quantitative degree of capillary perfusion achieved by either the antegrade or retrograde technique. These results have important implications for planning strategies of myocardial protection and suggest that further investigation concerning the microvascular distribution of retrogradely delivered cardioplegic solution in human beings is merited. PMID- 8487564 TI - Retrograde versus antegrade delivery of cardioplegic solution in myocardial revascularization. A clinical trial in patients with three-vessel coronary artery disease who underwent myocardial revascularization with extensive use of the internal mammary artery. AB - The effects of retrograde and antegrade delivery of cardioplegic solution on myocardial function were evaluated and compared in 60 patients who underwent myocardial revascularization. All patients had three-vessel coronary artery disease, and the revascularization was done with extensive use of the internal mammary artery. Seventy-five percent of the distal anastomoses were performed with the internal mammary artery. Myocardial protection consisted of St. Thomas' Hospital cardioplegic solution, topical slushed ice, and systemic hypothermia (28 degrees C). The patients were randomly separated into two groups: group A (n = 30), who received antegrade cardioplegia, and group B (n = 30), who received retrograde cardioplegia. With the exception of the total dose of cardioplegic solution (p = 0.02), there was no significant difference between the two groups that concerned septal myocardial temperature at the moment of asystole and after infusion of the total dose of cardioplegic solution. Cardiac function was assessed before and after the patient was weaned from cardiopulmonary bypass. In the immediate postoperative period there was a significant increase in right atrial pressure of the patients who underwent antegrade cardioplegia. For the other registered parameters there was no significant difference either in the immediate postoperative period or 6 hours later. Release of creatine kinase MB isoenzyme was the same in the two groups. Clinical outcome in terms of mortality, prevalence of perioperative infarction, prevalence of low cardiac output, and rhythm and conduction disturbances was similar in both groups. Technical problems related to cannulation and decannulation of the coronary sinus were not encountered. Multivariate analysis showed that occlusion of the left anterior descending coronary artery (p = 0.012) is an essential contraindication of antegrade delivery of cardioplegic solution. Analysis of the patients with an occlusion of the left anterior descending coronary artery who underwent antegrade (n = 9) and retrograde (n = 10) cardioplegia showed a significant difference in the total dose of cardioplegic solution (p = 0.02) and septal myocardial temperature at the moment of asystole (p = 0.008) and after infusion of the total dose of cardioplegic solution (p = 0.015). The mean arterial systolic blood pressure in the antegrade group was significantly lower than in the retrograde group (p = 0.003). Preservation of the left ventricular stroke work index was significantly better in the retrograde group (namely, 85% of its initial value versus 71% in the antegrade group, p = 0.0116).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487565 TI - Superiority of controlled surgical reperfusion versus percutaneous transluminal coronary angioplasty in acute coronary occlusion. AB - Although percutaneous transluminal coronary angioplasty is successful in more than 90% of patients after acute coronary occlusion, overall mortality remains approximately 10% with higher subgroup mortality (i.e., occlusion of the left anterior descending coronary artery, multivessel disease, age older than 70 years, cardiogenic shock) and early recovery of regional wall motion is marginal. This multicenter report shows that controlled surgical reperfusion in patients with acute coronary occlusion reduces overall and subgroup mortality and restores substantial early contractility. In a survey from six institutions, 156 consecutive patients with acute coronary occlusion documented by angiography underwent surgical revascularization with controlled reperfusion using amino acid enriched blood cardioplegic solution on total vented bypass. Ventricular wall motion was studied by echocardiography or multiple gated acquisition scan on postoperative days 5 to 7 and scored independently (0 = normal, 1 = mild hypokinesia, 2 = severe hypokinesia, 3 = akinesia, 4 = dyskinesia). Results are compared with results in 1203 patients with acute coronary occlusion treated by angioplasty in five reported medical series. Surgically treated patients were revascularized at longer ischemic intervals (6.3 versus 3.9 hours, p < 0.05) and had a greater incidence of left anterior descending occlusion (61% versus 43%, p < 0.05), multivessel disease (42% versus 22%, p < 0.05), and cardiogenic shock (41% versus 10%, p < 0.05), with 12 patients undergoing cardiopulmonary resuscitation en route to the operating room. Surgical results were superior in all categories, with overall mortality reduced from 8.7% after angioplasty to 3.9% after coronary bypass (p < 0.05). All surgical deaths occurred in patients with preoperative cardiogenic shock. Regional wall motion recovered significantly (score < 2) in 131 of 150 (87%) surgically treated patients with an average score of 0.9 +/- 0.8 (normal to mild hypokinesia) despite longer ischemic times. PMID- 8487566 TI - Plasma fentanyl levels in infants undergoing extracorporeal membrane oxygenation. AB - Plasma levels of fentanyl were analyzed in 12 infants undergoing extracorporeal membrane oxygenation who received a fentanyl bolus (5 to 10 micrograms/kg) followed by infusion at 1 to 6.3 micrograms/kg/hr. Fentanyl levels, averaging 11 samples/infant, were measured by radioimmunoassay (mean 19.7 +/- 35.7 ng/ml; n = 140). Eight of the infants, all with a primary diagnosis other than congenital diaphragmatic hernia, survived with relatively short (< 7 days) courses on extracorporeal membrane oxygenation; this group of infants did not develop tolerance to fentanyl and could be maintained on infusion rates of < 5 micrograms/kg/hr throughout. The four infants with congenital diaphragmatic hernia had longer extracorporeal membrane oxygenation runs and three did not survive; their plasma fentanyl levels were consistently higher and while the infusion rates were higher early on extracorporeal membrane oxygenation, they did not exceed 7 micrograms/kg/hr and actually decreased after 5 days on extracorporeal membrane oxygenation. Five infants (42%) received lorazepam in addition to fentanyl for at least one sampling time. The fentanyl infusion dose and plasma level were higher in the congenital diaphragmatic hernia nonsurvivors who did not receive lorazepam (p < 0.001). A decrease in fentanyl clearance correlated with renal dysfunction (p < 0.01). A bolus of fentanyl followed by infusion of relatively low doses (1 to 5 micrograms/kg/hr) provides adequate analgesia for infants on extracorporeal membrane oxygenation, particularly when it is supplemented with intravenous lorazepam whenever needed to control infant movement. PMID- 8487567 TI - Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors. AB - Brief case histories of three patients aged 58, 38, and 44 years are reported. All underwent cardiovascular operations. Subsequently hemostasis test abnormalities developed between the seventh and eighth postoperative days after exposure to bovine thrombin used with fibrin glue. These were characterized by an increased activated partial thromboplastin time (64 to 147 seconds), prothrombin time (19 to 24 seconds), bovine thrombin time (> 120 seconds) and a markedly reduced factor V level (< 10% in two patients and 16% in the third patient). A patient plasma dilution of 1 in 200 with a normal plasma pool was necessary to correct bovine thrombin time. No fast-acting or progressive inhibitor against factor V could be detected by coagulation tests, and fresh frozen plasma perfusion had no effect. Plasmapheresis was performed preventatively to avoid bleeding, and factor V levels stabilized at around 50% after two to four exchanges. Immunologic studies showed that the inhibitors were directed not only against bovine factors but also against human ones. Therefore factor V decrease could have been the result of rapid clearance from the circulation of complexes formed with a nonneutralizing inhibitor that is not detected by clotting tests. These antibodies were purified by standard methods and immunoaffinity. Fast immunization could be explained by a prior sensitization to bovine thrombin exposure during previous operations. It is suggested that bovine thrombin used with fibrin glue contains small amounts of factor V and may be responsible for these abnormalities. This is in agreement with previous literature reports. However, these described neutralizing factor V inhibitors, which were easily detected. PMID- 8487568 TI - Esophagectomy with or without thoracotomy. Is there any difference? AB - Two operative approaches for esophageal carcinoma were compared with respect to operative morbidity and mortality by means of multivariable analysis. From 1980 to 1986, 152 patients underwent resection by laparotomy and right-sided anterolateral thoracotomy with an intrathoracic anastomosis. From 1986 to 1989, 141 patients underwent resection by transhiatal blunt dissection with a cervical anastomosis. The stomach was the preferred organ for reconstruction. Paresis of the recurrent laryngeal nerve and leakage of the cervical anastomosis occurred significantly more often in the transhiatal group. Pulmonary complications occurred less frequently in the transhiatal group. In-hospital mortality (9% in the thoracotomy group and 5% in the transhiatal group) increased significantly with advanced age of the patients. Furthermore, it was significantly higher in case of colonic interposition as compared with reconstruction with the stomach. Long-term survival did not differ between the two groups. Especially for carcinomas in the distal part of the esophagus, transhiatal esophageal resection without thoracotomy seems to be an oncologically justifiable operation with a reduced morbidity and mortality. PMID- 8487569 TI - N2 lung cancer: outcome in patients with false-negative computed tomographic scans of the chest. AB - Over the past 13 years 681 consecutive patients have undergone computed tomographic staging and surgical staging of the mediastinum. Five hundred one tested negative for mediastinal lymph node enlargement by computed tomographic staging, and 37 of these patients had cancerous mediastinal lymph nodes at thoracotomy (n = 36) or mediastinoscopy (n = 1). The survival in this group of patients was analyzed according to T status, central or peripheral location of tumor, cell type, areas of mediastinum that are involved, and extent of nodal involvement with tumor. Twelve patients had central tumors, and 25 had peripheral tumors. Two of the patients in the central tumor group died postoperatively and only 2 others survived, whereas 12 of the 25 patients in the peripheral tumor group survived. Four of the 37 patients, 2 in each group, did not undergo resection, and all died. All but 2 of the 31 survivors who underwent resection received postoperative adjuvant x-ray therapy (23 patients), chemotherapy (1 patient), or x-ray therapy and chemotherapy (5 patients). The projected 2-year and 5-year survivals (Kaplan-Meier) were 40% and 28% for patients overall, 46% and 31% for those whose tumors were resected, 40% and 20% for those with resected central tumors, and 52% and 45% for those with resected peripheral tumors. None of these differences was significant. Cell type, location or number of locations of involved nodes, and the average percentage or maximum percentage of mediastinal node that was involved with tumor did not influence survival. The high negative predictive index for computed tomographic staging of the mediastinal lymph nodes and the observed 2-year and 5-year survivals in patients with false-negative computed tomographic scans of the chest justifies definitive thoracotomy without mediastinoscopy in most patients with a normal mediastinum on computed tomographic scan. PMID- 8487570 TI - Indications, risks, and results of completion pneumonectomy. AB - Completion pneumonectomy refers to an operation intended to remove what is left of a lung partially resected during a previous operation. The procedure is seldom indicated and, according to current medical literature, it carries a higher risk of operative mortality and morbidity than does standard pneumonectomy, especially when done for benign disease. Over the past 20 years, 60 consecutive patients aged 17 to 70 years and having a diagnosis of recurrent lung cancer (n = 28), new primary lung cancer (n = 13), or benign pleuropulmonary disease (n = 19) underwent completion pneumonectomy. The mean interval between the first operation and completion pneumonectomy was 30 months for patients with carcinoma and 215 months for patients with benign disease. For all patients, the previous thoracotomy incision was reopened and maneuvers such as rib resection, intrapericardial blood vessel ligation, division of the bronchus first, local application of glues and hemostatic agents, and bronchial reinforcement were routinely used. Six patients died during (n = 2) or after (n = 4) the operation, for an overall operative mortality of 10%. The rate was higher for patients with carcinoma (11.6%) than for patients with benign disease (5.9%). Actuarial 5-year survivals from the time of completion pneumonectomy were 48% for the entire population, 33% for patients with cancer, and 88% for patients with benign disease. These results suggest that completion pneumonectomy can be done with an operative risk similar to the one reported for standard pneumonectomy (6% to 10%). In addition, patients undergoing completion pneumonectomy have a reasonable prospect for long-term survival. PMID- 8487571 TI - Anatomic repair of transposition of great arteries with ventricular septal defect and aortic arch obstruction. One-stage versus two-stage procedure. AB - Between September 1, 1982, and March 1, 1992, 40 patients underwent anatomic repair of transposition of the great arteries, ventricular septal defect, and aortic arch obstruction. In group I, 26 patients (65%) underwent repair in a two stage procedure, phases A and B. Phase A included repair of the aortic arch obstruction with (16 patients) or without (10 patients) pulmonary artery banding through a left thoracotomy (mean age 18.7 +/- 23.4 days). There were three deaths and three reoperations. Phase B included an arterial switch operation with closure of the ventricular septal defect (mean age 95.5 +/- 122 days). There were five early deaths and two late deaths. Eight patients required reoperation. Mean delay between phase A and phase B was 77.5 +/- 109 days. In group I, there were eight early and two late deaths, and 11 patients required reoperation. The mean stay in the intensive care unit was 24.7 +/- 20 days. Mean follow-up of 59.6 +/- 21.4 months was completed in all survivors. All but one were in New York Heart Association class I without medication. Actuarial survival rate and rate of freedom from reoperation at 5 years were 57.5% and 49.9%, respectively. In group II, 14 patients (35%) had a one-stage procedure through midsternotomy: an arterial switch operation with closure of the ventricular septal defect and repair of the aortic arch obstruction (mean age 10.2 +/- 5.5 days). There were two early deaths (14.2%) and one late death after reoperation for overlooked multiple ventricular septal defects. Two patients required reoperation. The mean stay in the intensive care unit was 11.7 +/- 2.5 days. Mean follow-up of 22.4 +/- 16.7 months was achieved in all survivors. They were all in New York Heart Association class I without medication. Actuarial survival rate and rate of freedom from reoperation at 3 years were 78.5% and 81.5%, respectively. The one stage procedure allowed complete repair in neonates without the need for multiple operations. We believe that it may decrease early mortality rates (14.2% versus 30.7%), reduce the reoperation rate and cumulative stay in the intensive care unit (11.7 days versus 24.7 days, p = Not significant), and significantly decrease the overall rate of morbidity (p < 0.01). However, requirements for surgical intervention with a one-stage or a two-stage procedure must include accurate assessments of intracardiac and aortic arch anatomy. PMID- 8487573 TI - Mesothelioma: an incurable, nonsurgically treatable disease. PMID- 8487572 TI - Degeneration of aortic valve allografts in young recipients. AB - Aortic allograft fibrocalcification and valvular insufficiency have been observed in patients less than 3 years of age at initial replacement of the left ventricular outflow tract. From June 1985 through May 1992, 47 children have undergone aortic root replacement with cryopreserved aortic valve allografts. Thirty-three children were 3 years of age or older and 14 were less than 3 years of age at operation. In the older patient group, there were three (9%) hospital deaths and one child underwent cardiac transplantation 30 hours after aortic root replacement because of left ventricular failure. Clinical follow-up of the 29 surviving older children is from 4 months to 6.6 years (mean 3.0 years). One patient was lost to follow-up. Two children (7%) have required reoperation, but primary allograft degeneration was not observed. In the younger patient group, there were three (21%) hospital deaths. Follow-up ranged from 2.5 months to 4.7 years (mean 2.3 years). Among 11 operative survivors, one late death resulted from a pulmonary embolus. Seven of 10 (70%) remaining allograft recipients had progressive allograft calcification or insufficiency. Six of them have required reoperation to explant the allograft, and one child is currently receiving cyclosporine therapy with the original valve allograft. The cause of allograft failure is possibly immunologic. The prevalence of early aortic valve allograft degeneration has prompted the consideration of nonviable allografts or xenografts, pulmonary autografts, or minimal immunosuppression as alternatives when left ventricular outflow tract reconstruction is necessary in children less than 3 years of age. PMID- 8487574 TI - Solitary bone plasmacytoma of rib presenting as a superior sulcus tumor. PMID- 8487575 TI - Transesophageal echography as an emergency diagnostic tool for acute aortic dissection. PMID- 8487576 TI - Surgical correction of a recurrent aneurysm of the ascending aorta simulating pulmonary stenosis. PMID- 8487577 TI - Aneurysm of saphenous vein graft used for aorta-coronary bypass, resembling an anterior mediastinal mass. PMID- 8487578 TI - Aortic aneurysm after subclavian arterial flap angioplasty for coarctation of the aorta. PMID- 8487579 TI - A variant course of posterior descending artery. PMID- 8487580 TI - Characteristics of the inhibition of human promyelocytic leukaemia HL60 cell growth by S-D-lactoylglutathione in vitro. AB - The mechanism of the inhibition of proliferation of human leukaemia 60 (HL60) cells by S-D-lactoylglutathione in vitro was investigated. The median inhibitory concentration IC50 value was 66 microM (95% C.I. 50-87 microM; n = 18). The inhibition of leukaemia cell growth required exposure of HL60 cells to S-D lactoylglutathione (and metabolites) for 12 h, with maximum growth inhibition achieved after 24 h. Removal and replacement of culture medium within the initial 12 h of culture prevented inhibition of growth and toxicity. S-D lactoylglutathione was consumed within the initial 3 h of culture. Pretreatment of culture medium containing 10% foetal calf serum for 3 h produced no subsequent inhibition of HL60 cell growth. Incubation of HL60 cells in culture medium with low serum content (5% v/v) produced a decreased rate of cell proliferation and a decreased response to S-D-lactoylglutathione. S-D-lactoylglutathione inhibited uptake of 3H-thymidine into DNA in the third hour of culture where the median inhibitory concentration IC50 value was 74 microM (95% C.I. 51-102; n = 10). The mechanism of inhibition of HL60 cell growth by S-D-lactoylglutathione is unknown but may be cell cycle related, mediated by inhibition of DNA synthesis and involve an active metabolite which may be removed and/or inactivated by a change in culture medium. PMID- 8487581 TI - Effects of dolastatins on human B-lymphocytic leukemia cell lines. AB - Dolastatins are naturally occurring peptides isolated from marine animals and are known to be potent anti-neoplastic agents. Here, the three compounds dolastatin 10 (Dola 10), dolastatin 15 (Dola 15) and deo-dolastatin 10 (Deo-Dola 10) were added to cultures of two human chronic B-leukemia cell lines, JVM-2 and EHEB. The three dolastatins (Dola 10 > Dola 15 > Deo-Dola 10) inhibited cell proliferation and immunoglobulin production. Decreased cell growth and lack of accumulation of immunoglobulin was not caused by cytotoxicity as cell viability in the cultures remained high. The unchanged surface marker immunoprofiles during treatment and a predominance of treated cells in S and G2/M phase suggested cytostatic rather than directly cytotoxic effects. Exposure to these reagents increased quickly, albeit only short c-myc and bcl-2 mRNA expression. These results indicate that the three dolastatins are potent inhibitors of leukemic B-cell proliferation. PMID- 8487582 TI - Detection of circulating monoclonal lymphocytes in multiple myeloma patients by analysis of gene rearrangements: correlation with progressive disease. AB - Multiple myeloma is characterized by the proliferation of a monoclonal plasma cell population that essentially spreads in the bone marrow. However, immunological data and studies on clonal gene rearrangements have provided evidence for circulating malignant B-lymphocytes. Herein, we report on the detection and clinical significance of monoclonal lymphocytes in the peripheral blood of multiple myeloma patients. Applying the analysis of immunoglobulin gene rearrangements, clonal circulating lymphocytes were found in 8 out of 37 patients. In three of these eight patients, DNA from the bone marrow could be examined as well, and the same gene rearrangement as in peripheral blood was detected. This observation indicates that the monoclonal lymphocytes in the peripheral blood are part of the malignant plasma cell clone in the bone marrow. There was a strong correlation between progressive stage III disease and the detection of circulating tumour cells, whereas neither in stable stage III nor stage I disease could clonal gene rearrangements be detected. Our findings indicate the high incidence of monoclonal lymphocytes in the peripheral blood from patients with progressive multiple myeloma. This may be of importance with respect to cell harvesting strategies for autologous peripheral stem cell transplantation in multiple myeloma. PMID- 8487583 TI - Intracellular concentrations of mitoxantrone in leukemic cells in vitro vs in vivo. AB - The aim of this study was to determine the intracellular pharmacokinetics of mitoxantrone in vivo and to use these results to establish how leukemic cells should be incubated to perform clinically relevant in vitro studies of this drug. Blood samples were obtained from 11 patients with acute nonlymphoblastic leukemia at certain intervals up to 20 h after the infusion of mitoxantrone 12 mg/m2. Plasma and leukemic cells were separated and the drug concentrations were determined with HPLC. Before treatment, leukemic cells from 12 patients were incubated with 0.02, 0.05, 0.1, 0.2 and 1.0 microM mitoxantrone for 1-4 h and thereafter cultured in suspension culture for 20 h; during this time cell samples were taken at certain intervals for drug determination. In cells incubated with 0.05 and 0.2 microM mitoxantrone the cytotoxic effect was measured with the DiSC assay after cultivation for 4-5 days. In vivo, the intracellular levels exceeded the plasma concentrations already at the end of infusion and after 2 h the intracellular concentrations were 200-300 times higher than in plasma. In vitro, the intracellular steady state level of mitoxantrone was reached after 1-2 h and there was a pronounced intracellular retention even after 20 h culture in drug free medium. Incubation with 0.05 microM during 1 h gave intracellular concentrations of mitoxantrone similar to those achieved in vivo. This incubation concentration gave a mean cytotoxic effect of 53% living cells measured with the DiSC assay, which gives good possibilities to discriminate between mitoxantrone sensitive and unsensitive cells. We believe that exposing leukemic cells in vitro for in vivo mimicking mitoxantrone concentrations could increase the clinical relevance of predictive assays. PMID- 8487584 TI - Effect of verapamil on daunorubicin accumulation in human leukemic cells with different levels of MDR1 gene expression. AB - The purpose of the present study was to evaluate the distribution of the multiple drug resistance phenotype in leukemic cells with different levels of mdr1 gene expression. Peripheral leukemic cells from 8 patients (5 with detectable and 3 with undetectable mdr1 RNA levels) were incubated with daunorubicin (1 microM) in the absence and presence of verapamil (6.6 microM). Daunorubicin accumulation in individual cells was analysed by flow cytometry. Verapamil increased (16-45%) the mean daunorubicin accumulation in 7 of the 8 cell samples. In cells from 4 of these 7 patients, the fluorescence histograms showed a general increase of daunorubicin accumulation. The increase was limited to a small subpopulation of cells in one patient. In the remaining two patients an increase of daunorubicin accumulation was seen in the majority of cells, while cells with the highest accumulation were unaffected. In conclusion, verapamil can increase daunorubicin accumulation in leukemic cells with and without detectable mdr1 gene expression and the increase seems to affect the majority of the cell population. PMID- 8487585 TI - Delineation of translocation t(15; 17) in acute promyelocytic leukemia by chromosomal in situ suppression hybridization. AB - In this study we demonstrate the feasibility of chromosomal in situ suppression (CISS) hybridization to detect the translocation t(15; 17) in metaphase spreads of patients with acute promyelocytic leukemia. Using DNA libraries from sorted human chromosomes 15 and 17 the translocation t(15; 17) can be unequivocally identified even if the spread and the morphology of the chromosomes are poor. The sensitivity of CISS hybridization is compared with the sensitivity of conventional G-banded karyotypes. PMID- 8487586 TI - Combination of classical and interphase cytogenetics to investigate the biology of myeloid disorders: detection of masked monosomy 7 in AML. AB - Numerical abnormalities of chromosome 7 were detected by using fluorescence labeled in situ hybridization (FISH) procedure with a centromere-specific probe in four cases of acute myeloid leukemia (AML) and three cases of myelodysplastic syndromes (MDS). Comparison of these results with classical cytogenetic (CC) data demonstrated a good correlation between the two methods. FISH confirmed the finding of monosomy 7 in all patients who demonstrated this abnormality by CC. Two AML patients who did not show monosomy 7 by CC were unexpectedly found to contain this abnormality in 39.8% and 17% cells when examined by FISH. Given that our modified FISH method consistently yielded > 96% hybridization efficiency, these findings constitute an unexpected but real presence of monosomy 7 in a substantial number of interphase cells that had remained undetected by classical karyotyping. Finally, a number of maturing myeloid cells including granulocytes also demonstrated monosomy 7 by FISH, thereby confirming the ability of malignant cells to undergo differentiation. We conclude that FISH constitutes a highly sophisticated molecular technique which can be extremely useful in select cases for detecting 'masked monosomy 7' as well as helping to determine the lineage of terminally mature cells in AML, thereby providing a handle on the effects of cytokines or chemotherapy on normal vs leukemic clones. PMID- 8487587 TI - Acute myeloblastic leukemia (ANLL-M2) with t(8;21)(q22;q22) variant expressing lymphoid but not myeloid surface antigens with a high number of G-CSF receptors. AB - Leukemic cells from an 8-year-old girl with ANLL-M2 expressed precursor B-cell antigen CD19, but none of the myeloid antigens CD11b, CD13, CD14 and CD33. After culture, the cells expressed CD11b and CD13. The cells carried a high number of granulocyte colony-stimulating factor (G-CSF) receptors. In chromosome analysis, metaphase cells were obtained only in the case of culture with G-CSF. The karyotype was a variant of t(8;21)(q22;q22). Southern blot analysis revealed rearrangement of the AMLI gene located on chromosome 21. These observations may suggest that even without myeloid surface antigens and with precursor B-cell antigen, ANLL-M2 with t(8;21)(q22;q22) has apparent myeloid characteristics. PMID- 8487588 TI - The history of HTLV-I. PMID- 8487589 TI - HTLV-I and adult T-cell leukemia. PMID- 8487590 TI - Discovery of HTLV-1. PMID- 8487591 TI - Expression of sialyl-Lewis(x) on CD10-positive normal bone marrow cells. PMID- 8487592 TI - Comparison of in vitro effects of two thiol-containing drugs on human neutrophils hydrogen peroxide production. AB - During inflammatory disorders, potentially destructive reactive oxygen species, especially hydrogen peroxide, are produced by activated phagocytic cells. It was demonstrated in vitro that mesna and N-acetylcysteine (NAC), mucolytic thiols, have antioxidant properties. An estimation was made of the 50% inhibitory concentration (IC50) of mesna and NAC for PMA-induced H2O2 production by human neutrophils, the results being 70 mcM and 77 mcM, respectively. The mechanism which governs mesna and NAC reactions results from a scavenging effect of H2O2: the calculated IC50s of this effect were 30 mcM and 42 mcM, respectively, in free cellular experimentation. The results suggest that mesna and NAC might be used as antioxidants in aerosols to prevent tissue damage inflicted by this reactive oxygen species, especially in the lungs. PMID- 8487593 TI - Studies on the tissue distribution of liposome-associated clofazimine, an antileprosy drug. AB - Clofazimine, a potent antimycobacterial drug, being highly lipophilic accumulates in fatty tissue and in the reticuloendothelial system causing dose-dependent side effects. In this study, the distribution of the free drug and liposome-associated drug was compared after intravenous administration in mice. Differences in the distribution of the drug were observed in the liver, spleen, kidney and lung tissues when injected as free drug and as liposome-associated drug. Following intravenous challenge with the free drug, the drug accumulated quickly and high concentrations of the drug were seen in the spleen, liver, kidney and lung even after 24 h, indicating poor clearance. However, with liposome-associated drug, increased levels were seen in liver, spleen and lung at 1 h with levels falling considerably at 24 h, with no accumulation in the kidney either at 1 h or 24 h after challenge. Clofazimine associated with neutral liposomes was preferentially targetted to spleen and lung, positively charged liposome-associated drug accumulated more in the lungs than in other tissues, while negatively charged liposome-associated drug was directed to liver and spleen. The results suggest that inclusion of clofazimine into liposome not only targets the drug to the organs concerned but also facilitates clearance of the drug, resulting in little accumulation. Also, renal accumulation is much lower as compared to the free drug. This suggests the potential usefulness of liposome as a carrier for clofazimine, thereby reducing the harmful side effects due to excessive accumulation of the drug. PMID- 8487594 TI - The application of computerized analysis of nuclear images and multivariate analysis to the understanding of the effects of antineoplastic agents and their mechanism of action. AB - The present work involves the creation of a model that makes the rapid study of anticancer drugs possible. In order to make possible the multilevel study of antineoplastic derivatives (their effects on cell proliferation, their cell kinetics, their chromatin texture and the study of their potential operating mechanisms), the computerized analysis of nuclear images linked to multivariate analysis was chosen, and, in so doing, took into account 15 computer-calculated morphonuclear parameters for Feulgen-stained cell nuclei. In order to validate the method it was subjected to a series of well-known cancer drugs. The present results are in agreement with those obtained by conventional methods similar to those used for the study of the cytotoxicity of anticancer molecules or their effect on cell kinetics. Multivariate analysis applied to the parameters described by image analysis should make possible the rapid study of new anticancer drugs together with the rapid orientation of studies undertaken to ascertain their operating mechanisms. PMID- 8487595 TI - Liver damage and plasma concentrations of paracetamol and its metabolites after paracetamol overdosage in mice. AB - The effects of single oral and intraperitoneal (i.p.) overdoses of paracetamol (500 mg/kg) were studied in mice. The correlation between hepatocellular damage and plasma levels of paracetamol metabolites derived from the oxidative pathway were also investigated. Animals were killed at different intervals (1, 2.5 and 6 h) after drug administration. Plasma concentrations of paracetamol and its sulphate, glucuronide, cysteine and mercapturate conjugates were determined by HPLC. Paracetamol plasma levels were significantly higher at 1 and 2.5 h after i.p. administration as compared to oral administration (p = 0.01 and p = 0.02, respectively). Plasma levels of mercapturic acid conjugate were significantly higher at 6 h after i.p. administration (p = 0.04). After 6 h, animals given oral paracetamol showed significantly less necrosis than animals given i.p. paracetamol (p = 0.03). Plasma levels of mercapturate conjugate at 6 h showed a significant correlation with the severity of liver necrosis (r = 0.64; p = 0.02). The results suggest that i.p. paracetamol seems to be more adequate for hepatotoxicity studies in mice. PMID- 8487596 TI - A new method of blood sampling and determination of the local anesthetic agent lidocaine in dentistry. AB - Blood levels of local anesthetic agents after application in dentistry have been determined only in peripheral venous blood. A method of withdrawing blood from the alveolus after extraction of a tooth was developed. With a new simple gas chromatographic method with a low detection limit, concentration of lidocaine was determined. A correlation between the blood levels of lidocaine and the type of anesthesia and the localization of the extracted teeth was found. PMID- 8487597 TI - Effects of pinacidil and acetylcholine on early afterdepolarization of atrial fibers in mouse heart. AB - The effects of pinacidil and acetylcholine (Ach) on action potential (AP) and early afterdepolarization (EAD) were investigated in mouse atrial fibers. Under treatment with pinacidil the AP and EAD were affected only with the concentration of 8 x 10(-5) M, which inhibited EAD but did not affect AP except for only a minor reduction of action potential duration (APD). After withdrawal of pinacidil, the inhibitory effect of EAD was enhanced. Under treatment with Ach (2 x 10(-7) M), AP was not changed except the APD, which was significantly reduced, and the EAD was completely abolished. Withdrawal of Ach produced a rebound increase in APD and led to induction of EAD or promoted EAD to more extensive level such as appearance of long second plateau. Atropine (1 x 10(-7) M) abolished the rebound effect caused by withdrawal of Ach. The mechanism of EAD generation induced by removing Ach is discussed. PMID- 8487598 TI - The increase in erythrocyte deformability in patients treated with nicardipine or nimodipine. AB - A study was made of a total of 50 patients, 36 females and 14 males, with an average age of 51.3 +/- 11.71 years (range 19-71). The group consisted of outpatients who came to the neurology clinic suffering from vascular headache or other symptomatic complaint of vascular type. In all cases, the existence of an organic neurological pathology had been considered and rejected. All patients who were smokers or suffering from hypertension were excluded, as well as those who had abnormal lipid or glucose values or who were on drug treatment for other reasons. The basal erythrocyte deformability value was determined and the patients divided into two random homogeneous groups. One of the groups was treated with nimodipine (90 mg/d) and the other with nicardipine (60 mg/d) for a period of two months. After this treatment period a further determination of the erythrocyte deformability was carried out. In the group treated with nimodipine, the erythrocyte deformability varied from 45.5 +/- 7.4 mcl/s to 50.35 +/- 12.02 mcl/s (p = 0.07123). In the group treated with nicardipine, these values varied from 45.96 +/- 7.35 mcl/s to 56.21 +/- 12.72 mcl/s (p = 0.00079). It was concluded that in both groups of patients, after two months treatment with these calcium antagonists, there was an improvement in erythrocyte deformability and, therefore, in blood fluidity, although only the nicardipine-treated group reached statistically significant levels. PMID- 8487599 TI - [Does olsalazine influence spermatogenesis?]. PMID- 8487600 TI - [Investigations of drugs from regional centers]. PMID- 8487601 TI - [Scopolamine against hypersalivation]. PMID- 8487602 TI - [Adjusting for studied districts can be useful]. PMID- 8487603 TI - [A highly unethical and distasteful advertising campaign]. PMID- 8487604 TI - [Can time trends for results after vascular surgery be misunderstood?]. PMID- 8487605 TI - [It is too easy to get exemption from military service]. PMID- 8487606 TI - [Simple payment by results in hospital care]. PMID- 8487607 TI - [Egg donation. A desirable therapeutic method?]. PMID- 8487608 TI - [The topic of WHO for the World Health Day: try to prevent violence]. PMID- 8487609 TI - [10 years with HIV and AIDS. Clinical experiences]. PMID- 8487610 TI - [Polyamines in health and disease]. PMID- 8487611 TI - [Removal of urinary tract calculi. How invasive should the treatment be?]. PMID- 8487612 TI - [A case report. Erythropoietin replaced blood transfusion]. PMID- 8487613 TI - [Is problem-based learning good? A research review]. PMID- 8487614 TI - [Benzodiazepines. Physicians in the public service and industry: time to take responsibility for abuse of the drug]. PMID- 8487615 TI - [The Institute for Medical Education. The special teaching function of the Karolinska Institute]. PMID- 8487616 TI - [Mentally disturbed juvenile delinquents. Immigrants are more often sentenced to imprisonment]. PMID- 8487617 TI - Elongation predominates over desaturation in the metabolism of 18:3n-3 and 20:5n 3 in turbot (Scophthalmus maximus) brain astroglial cells in primary culture. AB - The origin of docosahexaenoic acid (DHA, 22:6n-3) that accumulates in turbot brain during development was investigated by studying the incorporation and metabolism via the desaturase/elongase pathways of [1-14C]-labelled polyunsaturated fatty acids (PUFA) in primary cultures of brain astrocytic glial cells. There was little specificity evident in the total incorporation of PUFAs into the turbot astrocytes. However, specificity was apparent in the distribution of the various PUFAs among the individual lipid classes. In particular, there was very specific incorporation of [14C]arachidonic acid (AA, 20:4n-6) into phosphatidylinositol balanced by a lower incorporation of this acid into total diradyl glycerophosphocholines. [14C]-Linolenic acid (LNA, 18:3n-3) and [14C]eicosapentaenoic acid (EPA, 20:5n-3) were metabolized via the desaturase/elongase pathways to a significantly greater extent than [14C]linoleic acid (18:2n-6) and [14C]AA. The turbot astrocytes expressed very little delta 5 desaturase activity and only low levels of delta 4 desaturation activity. Although the percentages were small, approximately 4-5 times as much labelled DHA was produced from [14C]EPA compared with [14C]LNA. However, it was concluded that very little DHA in the turbot brain could result from the metabolism of LNA and EPA in astrocytic glial cells. PMID- 8487618 TI - Detection of [U-13C]eicosapentaenoic acid in rat liver lipids using 13C nuclear magnetic resonance spectroscopy. AB - Fatty acid carbons are well-resolved in 13C nuclear magnetic resonance (NMR) spectra of lipid extracts, but application of this methodology to the metabolism of 13C-labelled fatty acids has not yet been reported. In the present study, 13C NMR was used to monitor the presence of 98% [U-13C]eicosapentaenoic acid (EPA) in liver and carcass lipids 24 h after it had been injected into the stomach of a rat. Natural abundance 13C NMR spectra of liver total fatty acid extracts were obtained from four control rats for comparison. At 24 h post-injection, quantitative high resolution 13C NMR showed 13C enrichment in liver fatty acid extracts was present mainly at olefinic and at the n-1 to n-4 carbons, but 13C signal intensities for C-1 to C-4 of [U-13C]EPA were markedly reduced or absent. Small 13C resonances, possibly indicative of some 13C incorporation into docosahexaenoic acid and saturated or monounsaturated fatty acids, were present in spectra of liver fatty acids. Liver and carcass fatty acid composition was similar in both the controls and the EPA-injected rat, suggesting little accumulation of the injected [U-13C]EPA after 24 h. We conclude that the carbon specific data provided by 13C NMR of lipid extracts may be useful in monitoring the fate of individual carbons during tracer studies using 13C-labelled fatty acids. PMID- 8487619 TI - Positional distribution of n-3 fatty acids in triacylglycerols from rat adipose tissue during fish oil feeding. AB - The present study was designed to investigate the metabolism of the n-3 polyunsaturated fatty acids (PUFA) in adipose tissue and its dependence upon dietary factors. Changes in the positional distribution of the fatty acids in triacylglycerols from retroperitoneal adipose tissue were studied as a function of time on rats fed for 4 wk a diet enriched with fish oil. The stereospecific analysis of triacylglycerols by Grignard degradation. This was followed by synthesis of rac-phosphatidic acids and treatment with phospholipase A2. In the triacylglycerols of the fish oil diet, 57% of the total n-3 fatty acids were in position 3, i.e., two-thirds of 20:5n-3 and 22:5n-3 were esterified in sn-3 position, whereas 22:6n-3 was equally distributed in positions 2 and 3. After 4 wk of feeding fish oil, the fatty acid composition of adipose tissue triacylglycerols reached a steady state. Half of the n-3 fatty acids were found in position 3, namely 75% of 22:5n-3, 50% of 20:5n-3 and 18:4n-3 and 45% of 22:6n 3, the latter being equally distributed in positions 2 and 3. This pattern of distribution resembled that found in triacylglycerols of the fish oil diet, except for a higher proportion of 20:5n-3 in adipose tissue in position 1 at the expense of position 3. Throughout the 4-wk period of fish oil feeding, the distribution pattern of minor n-3 fatty acids (18:4n-3 and 22:5n-3) in adipose tissue triacylglycerols remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487620 TI - Relationship between mouse liver delta 9 desaturase activity and plasma lipids. AB - This study was undertaken to investigate the total plasma fatty acid composition and the relationship between plasma triacylglycerol (TG) levels and liver delta 9 desaturase activity in mice fed n-3 and/or n-6 fatty acid or hydrogenated coconut oil (HCO) (maximum 25 mg/g) supplemented diets. Generally, plasma TG levels and delta 9 desaturase activity were inversely correlated with the ratio of the sum of long chain n-6 fatty acids to 18:2n-6 and to the ratio of the sum of long chain n-3 fatty acids to 18:n-3, but they were positively correlated with the ratio of products and substrates (18:1/18:0) of the enzyme in plasma total lipids. The n-3 fatty acid (mainly 20:5n-3) enriched diet, when compared to the HCO diet at 21 d, caused a significant reduction in plasma TG levels but not in delta 9 desaturase activity. However, a marked reduction in plasma TG content (50 60%) and delta 9 desaturase activity (55-70%) was observed when both 20:5n-3 and 18:3n-6 were supplemented in the diet. The plasma TG levels and delta 9 desaturase activity rose again when the animals were fed the HCO diet or chow. The results suggest that low dose supplementation of a mixture of n-3 (mainly 20:5n-3) and n-6 (18:3n-6) fatty acids modified both plasma TG content and liver delta 9 desaturase activity, in parallel. PMID- 8487621 TI - Age-related changes in delta 6 and delta 5 desaturase activities in rat liver microsomes. AB - Age-related changes in delta 6 desaturation of [1-14C]alpha-linolenic acid and [1 14C]linoleic acid and in delta 5 desaturation of [2-14C]dihomo-gamma-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon. Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate by taking into account the total amount of liver microsomal protein. delta 6 Desaturation of alpha-linolenic acid increased from 1.5 to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-gamma linolenic acid to arachidonic acid by delta 5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular, arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic acids varied little throughout the life span.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487622 TI - Cholesterol gallstone induction in hamsters reflects strain differences in plasma lipoproteins and bile acid profiles. AB - Because different strains of hamsters vary in their susceptibility to gallstones, the relationship between plasma lipoproteins, hepatic cholesterol, bile lipids and bile acid profile was examined during gallstone induction in strains of male Syrian hamsters from Charles River Lakeview (CHR), Biobreeder F1B (BIO) and Harlan Sprague-Dawley (HAR). Gallstones were induced by feeding a purified diet containing 0.4 or 0.8% cholesterol for 5 wk. Basal plasma total cholesterol was similar, but the hypercholesterolemia induced by dietary challenge was significantly lower in CHR than in HAR and BIO hamsters. Cholesterol-fed CHR hamsters transported cholesterol mainly in HDL (47%), whereas VLDL-C + IDL-C predominated in BIO and HAR hamsters, and their HDL transported only 28 and 38%, respectively. HAR hamsters accumulated the most hepatic cholesterol, revealed the highest cholate/cheno ratio, the lowest glycine/taurine ratio and hydrophobicity index. HAR also developed the fewest cholesterol gallstones (23%), while 64% of CHR and 58% of BIO hamsters had cholesterol gallstones and 34% of BIO hamsters developed pigment stones. Doubling dietary cholesterol from 0.4 to 0.8% doubled the incidence of cholesterol gallstones but exerted minimal impact on other parameters compared to strain differences. Thus, different strains of hamsters vary considerably with respect to biliary cholesterol, bile acid profile and formation of cholesterol gallstones associated with differences in plasma lipoprotein profiles. PMID- 8487623 TI - Hydrolysis of fish oils containing polymers of triacylglycerols by pancreatic lipase in vitro. AB - Fish oils containing different levels of polymers of triacylglycerols formed during autoxidation were incubated with pancreatic lipase to establish whether these polymers are substrates for lipase hydrolysis. With oils containing low amounts (less than 4%) of triacylglycerol polymers as substrates, both triacylglycerols and polymers of triacylglycerols were almost completely hydrolyzed, and fatty acid monomers and monoacylglycerols were the major lipid products. Under the same incubation conditions, some triacylglycerols remained intact when highly oxidized oils containing 20 or 30% triacylglycerol polymers were the substrate. The fatty acid composition of these residual triacylglycerols was almost identical to that of triacylglycerols present at the start of the assay. When fish oil containing 30% triacylglycerol polymers was incubated with the lipase, the component triacylglycerols and polymers of triacylglycerols were hydrolyzed at similar rates, and fatty acid dimers were detected as a product. It is concluded that the high molecular weight polymers of triacylglycerols present in oxidized fish oils can be hydrolyzed by pancreatic lipase in vitro. PMID- 8487624 TI - Stearidonic acid, an inhibitor of the 5-lipoxygenase pathway. A comparison with timnodonic and dihomogammalinolenic acid. AB - Leukotrienes have been shown to play an important role as mediators in various disease processes, including asthma and inflammation; thus, their synthesis is tightly regulated. The major precursor of leukotrienes is arachidonic acid (20:4n 6). Fatty acids which are structurally similar to 20:4n-6, such as eicosatrienoic acid (20:3n-6; dihomogammalinolenic acid) and eicosapentaenoic acid (20:5n-3; timnodonic acid) have been found to inhibit leukotriene biosynthesis. Because of the structural similarity of octadecatetraenoic acid (18:4n-3; stearidonic acid) with 20:4n-6, the present study was undertaken to determine whether stearidonic acid also exerts an inhibitory effect on the 5-lipoxygenase pathway. Human leukocytes were incubated with 18:4n-3 (20 microM or 10 microM), 20:5n-3 (20 microM) or 20:3n-6 (20 microM) and subsequently stimulated with 1 microM ionophore A23187 and 20:4n-6 (20 microM or 10 microM). The 5-lipoxygenase products were then measured by high-performance liquid chromatography. Leukotriene synthesis was reduced by 50% with 20 microM 18:4n-3 and by 35% with 10 microM 18:4n-3. Formation of 5S,12S-di-hydroxy-eicosatetraenoic acid and of 5 hydroxy-eicosatetraenoic acid was decreased by 25% with 20 microM 18:4n-3 and by 3% with 10 microM 18:4n-3. The inhibition observed with 20 microM 18:4n-3 appeared to be of the same order as that observed with 20 microM 20:5n-3; the inhibition observed with 18:4n-3 was shown to be dose-dependent. The inhibition produced by 20 microM 20:3n-6 was greater than that observed with either 20 microM 18:4n-3 or with 20 microM 20:5n-3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487625 TI - Identification of core aldehydes among in vitro peroxidation products of cholesteryl esters. AB - Synthetic cholesteryl 5-oxovalerate and 9-oxononanoate were used as reference standards for the isolation and identification of cholesteryl ester core aldehydes from tert-butyl hydroperoxide/Fe++ oxidation of synthetic and natural cholesteryl esters. The core aldehydes were recovered from the peroxidation products by thin-layer chromatography as the free aldehydes or the 2,4 dinitrophenylhydrazones and were identified, respectively, by gas-liquid chromatography (GLC) and by GLC combined with mass spectrometry (GC/MS) or by reverse-phase high-performance liquid chromatography (HPLC) and by HPLC with MS (LC/MS). The core aldehydes produced by peroxidation of cholesteryl linoleate were identified as mainly 9-oxononanoates of cholesterol and oxycholesterols, with smaller amounts of the 8-oxooctenoates, 10-oxodecenoates, 11-oxoundecenoates and 12-oxododecenoates. Peroxidation of cholesteryl arachidonate yielded 5 oxovalerates of cholesterol and the oxycholesterols as the main products with smaller amounts of the 4-oxobutyrates, 6-oxohexenoates, 7-oxoheptenoates, 8 oxooctenoates, 9-oxononenoates, 9-oxononadienoates and 10-oxodecadienotes. The oxycholesterols resulting from the peroxidation of the steroid ring were identified as mainly 7-keto-, 7 alpha-hydroxy- and 7 beta-hydroxy-cholesterols and 5 alpha,6 alpha- and 5 beta,6 beta-epoxy-cholestanols. Cholesteryl palmitate and oleate did not yield core aldehydes in the present peroxidation system. In these esters, the sterol and linoleic acid moieties appeared to be oxygenated at about the same rate, while the arachidonic acid moiety reacted more rapidly than did the sterol moiety. PMID- 8487626 TI - Characteristics of the thiobarbituric acid reactivity of human urine as a possible consequence of lipid peroxidation. AB - A 532 nm red pigment formed in the thiobarbituric acid (TBA) assay of human urine was characterized after separation of the pigment by high-performance liquid chromatography. The yield of the red pigment was somewhat higher at pH 2 than at pH 5; its development was not inhibited by ethylenediaminetetraacetic acid. The characteristics of the pigment were similar to those of the pigment derived from standard malonaldehyde. The amount of the pigment formed was roughly equal to the content of malonaldehyde derivatives estimated as 1-(2,4-dinitrophenyl)pyrazole. Pigment formation was significantly enhanced by t-butyl hydroperoxide (t-BuOOH) and ferric ions, which may be due to pigment formed from aldehydes other than malonaldehyde; the presence of these aldehydes was confirmed by the formation of the corresponding 2,4-dinitrophenylhydrazones. The amount of pigment produced from 24-h urine samples of 12 healthy subjects was estimated to be 26-95 nmol/kg, and 65-182 nmol/kg in the presence of t-BuOOH. These values are lower than those for urine of rabbit or rat. The TBA reactivity in the absence and presence of t BuOOH of human urine was not related to age or sex. The TBA reactivity of human urine collected in the afternoon and in the evening was higher than that of urine collected in the morning. PMID- 8487627 TI - Fatty acids in the lipids of Drosophila heads: effects of visual mutants, carotenoid deprivation and dietary fatty acids. AB - Lipids of Drosophila heads were extracted and separated by high-performance thin layer chromatography. Fatty acid compositions of major phospholipids as well as of triglycerides were analyzed by gas-liquid chromatography. Proportions of the major fatty acids (14:0, 16:0, 16:1, 18:0, 18:1, 18:2, 18:3) varied depending on the lipid analyzed. Docosahexaenoic acid (22:6), common in vertebrate photoreceptors and brain, and arachidonic acid (20:4), a precursor of eicosanoids, were lacking. A comparison of the fatty acid composition of the diet vs. the head suggested that Drosophila can desaturate but may not be able to elongate fatty acid carbon chains. Fatty acid analyses were carried out after the following visual system alterations: i) the transduction mutant where no receptor potential results from a deficit in phospholipase C; ii) an allele of eyes absent; iii) the mutant outer rhabdomeres absent which lacks visual pigment and rhabdomeres in the predominant type of compound eye receptor, rhabdomeres 1 through 6; and iv) carotenoid deprivation which reduces opsin and rhabdomere size. We also evaluated aging by comparing newly-emerged vs. aged wild-type flies. Alterations in fatty acid composition based on some of these manipulations were found. Based on comparisons between flies reared on media differing in C16 and C18, there is an indication that diet readily affects tissue fatty acid composition. PMID- 8487628 TI - Use of acetyl chloride/methanol for assumed selective methylation of plasma nonesterified fatty acids results in significant methylation of esterified fatty acids. AB - The albumin-bound nonesterified fatty acid pool in plasma, which represents a very small percentage of total plasma fatty acids, has previously been quantitated by a variety of methods. In the present study we determined that the nonesterified fatty acid concentrations in the plasma, quantitated by a popular method using acetyl chloride and methanol which is reported to be specific for methylation of nonesterified fatty acids in the presence of esterified fatty acids (i.e., without prior isolation of the plasma nonesterified fatty acids), were significantly overestimated due to cleavage and methylation of esterified fatty acids. Quantitation of the contaminating fatty acid from the esterified pool demonstrated that the amount of fatty acid cleaved from the esterified pool was enough to exceed the entire mass of nonesterified fatty acids. As an established method for comparison, we isolated nonesterified fatty acids from the plasma by thin-layer chromatography prior to methylation, using a number of simple precautions to limit oxidation. By performing all thin-layer chromatography steps in an atmosphere of nitrogen and by including fatty acid standards in the plasma with 0, 1, 2 or 4 double bonds, we were able to accurately and reproducibly determine the concentration of nonesterified fatty acids in the plasma, including arachidonate. We demonstrated that no oxidation occurred in the thin-layer chromatographic isolation of nonesterified fatty acids and that the coefficients of variation for repeat measurements of the same sample were < 11% using our reference method. Our data indicate that the use of acetyl chloride and methanol for assumed selective methylation of plasma nonesterified fatty acids results in significant methylation of esterified fatty acids. PMID- 8487629 TI - Profiling of arachidonic acid metabolites in rabbit platelets by radio gas chromatography. AB - A method for profiling arachidonic acid metabolites by radio gas chromatography (GC) is described. The incubation mixture of rabbit platelets with [14C]arachidonic acid was purified on a Sep-Pak C18 cartridge and derivatized with diazomethane, O-methylhydroxylamine and dimethyl-isopropylsilylimidazole. The recovery of total 14C-radioactivity was 93.1 +/- 7.2%. Loss of radioactivity during derivatization was negligible. Baseline separations for [14C]arachidonic acid and its metabolites were obtained in a single run within 45 min by GC using a synchronized accumulating radioisotope detector (GC/SARD). The recovery of radioactivity from the GC column was virtually 100%. The chemical structures of the metabolites were confirmed by GC/mass spectrometry; peaks of arachidonic acid metabolites were assigned by comparison of the methylene unit values with those of radioactive peaks in GC/SARD analyses. The intra-assay coefficients of variation in GC/SARD analyses were less than 10%. The method was used to map the profile of arachidonic acid metabolites formed by rabbit platelets in the presence of indomethacin, baicalein or glutathione. PMID- 8487630 TI - Evolution of the Zfx and Zfy genes: rates and interdependence between the genes. AB - A phylogenetic analysis of sex-chromosomal zinc-finger genes (Zfx and Zfy) indicates that the genes have not evolved completely independently since their initial separation. The sequence similarities suggest gene conversion in the last exon between the duplicated Y-chromosomal genes Zfy-1 and Zfy-2 in the mouse. There are also indications of conversion (or recombination) between the X- and Y chromosomal genes in the crab-eating fox and in the mouse. The method for estimating synonymous and nonsynonymous substitutions is modified by incorporating the substitutions in the twofold-degenerate sites in a novel way. The estimates of synonymous substitutions support the generation-time hypothesis in that the obtained rates are higher in mice (by a factor of 4.7) than in humans and higher in the Y-chromosomal genes (by a factor of 1.9) than in the X chromosomal genes. PMID- 8487631 TI - mtDNA diversity in rhesus monkeys reveals overestimates of divergence time and paraphyly with neighboring species. AB - Reconstructions of the human-African great ape phylogeny by using mitochondrial DNA (mtDNA) have been subject to considerable debate. One confounding factor may be the lack of data on intraspecific variation. To test this hypothesis, we examined the effect of intraspecific mtDNA diversity on the phylogenetic reconstruction of another Plio-Pleistocene radiation of higher primates, the fascicularis group of macaque (Macaca) monkey species. Fifteen endonucleases were used to identify 10 haplotypes of 40-47 restriction sites in M. mulatta, which were compared with similar data for the other members of this species group. Interpopulational, intraspecific mtDNA diversity was large (0.5%-4.5%), and estimates of divergence time and branching order incorporating this variation were substantially different from those based on single representatives of each species. We conclude that intraspecific mtDNA diversity is substantial in at least some primate species. Consequently, without prior information on the extent of genetic diversity within a particular species, intraspecific variation must be assessed and accounted for when reconstructing primate phylogenies. Further, we question the reliability of hominoid mtDNA phylogenies, based as they are on one or a few representatives of each species, in an already depauperate superfamily of primates. PMID- 8487632 TI - Nucleotide sequence of the D-loop region of the sperm whale (Physeter macrocephalus) mitochondrial genome. AB - We have amplified, by the polymerase chain reaction, and have sequenced the D loop region of the mitochondrial DNA from the sperm whale (Physeter macrocephalus). The sperm whale D-loop was aligned with D-loop sequences from four other cetaceans (Commerson's dolphin, orca, fin whale, and minke whale) and an out-group (cow). This alignment showed the sperm whale sequence to be larger than that of other cetaceans. In addition, some sequence blocks were highly conserved among all six species, suggesting roles in the functioning of mitochondrial DNA. Other blocks that were previously reported to be well conserved among cetaceans showed little sequence conservation with the sperm whale D-loop, which argues against the functional importance of these sequence blocks in cetaceans. PMID- 8487633 TI - Molecular studies on two variant repeat types of the common cetacean DNA satellite of the sperm whale, and the relationship between Physeteridae (sperm whales) and Ziphiidae (beaked whales). AB - In the sperm whale (Physeter macrocephalus) two different repeat types (A and B) of the common cetacean DNA satellite were identified. The evolution of each group of repeats appears to be independent from that of the other. The sequence similarity between the two groups is less than the similarity between group A and repeats of the satellite in related whale species. The systematic relationship within and between the families Physeteridae (sperm whales) and Ziphiidae (beaked whales) was addressed by both sequence analysis of the satellite and comparisons with the families Delphinidae and Phocoenidae. The mysticete blue whale (Balaenoptera musculus) was used as an outgroup in the comparisons. The molecular phylogeny, when maximum-parsimony analysis and the neighbor-joining method were used, grouped together species of each family. At the family level the ziphiids grouped closet to the families Phocoenidae and Delphinidae. The similarities between the common cetacean satellite of the blue whale and the sperm whale were greater than those between the blue whale and the other odontocetes included, suggesting that the evolution of the satellite is slower in the sperm whale than in the other odontocetes. PMID- 8487634 TI - Intraspecific DNA sequence variation of the mitochondrial control region of white sturgeon (Acipenser transmontanus). AB - Intraspecific sequence variation in the D-loop region of mtDNA in white sturgeon (Acipenser transmontanus), a relict North American fish species, was examined in 27 individuals from populations of the Columbia and Fraser rivers. Thirty-three varied nucleotide positions were present in a 462-nucleotide D-loop sequence, amplified using the polymerase chain reaction. Bootstrapped neighbor-joining and maximum-parsimony trees of sequences from 19 haplotypes suggest that the two populations have recently diverged. This is consistent with the hypothesis that the Columbia River, a Pleistocene refugium habitat, was the source of founders for the Fraser River after the last glacial recession. On the basis of a divergence time of 10-12 thousand years ago, the estimated substitution rate of the white sturgeon D-loop region is 1.1-1.3 x 10(-7) nucleotides/site/year, which is comparable to rates for hypervariable sequences in the human D-loop region. Furthermore, the ratio of mean percent nucleotide differences in the D-loop (2.27%) to that in whole mtDNA (0.54%, as estimated from restriction-enzyme data) is 4.3, which is similar to the fourfold-to-fivefold-higher substitution rate estimated for the human D-loop. The high nucleotide substitution rate of the hypervariable region indicates that the vertebrate D-loop has potential as a genetic marker in molecular population studies. PMID- 8487635 TI - Phylogenetic relationships in Drosophila: a conflict between molecular and morphological data. AB - Grimaldi's recent cladistic classification of genera in the family Drosophilidae, based on adult morphological characters, is evaluated for those taxa for which alcohol dehydrogenase DNA sequences are also available. These data allow us to look at relationships of the Drosophila subgenera Sophophora and Drosophila with the Hawaiian Drosophila (Idiomyia) and with Scaptomyza, when Scaptodrosophila is used as an outgroup. The molecular data give strong support for the broad relationships hypothesized by Throckmorton, who contended that the subgenus Sophophora is a sister group to the remaining ingroup taxa. The Drosophila subgenus Engiscaptomyza, which Throckmorton regarded as intermediate between the Idiomyia (Hawaiian Drosophila) and Scaptomyza, is shown to be much more closely allied with Scaptomyza, in agreement with Grimaldi's results from adult morphology. The Hawaiian taxa, both Idiomyia and Scaptomyza, are firmly located as a sister group to the subgenus Drosophila, and these in turn all form a sister group to the subgenus Sophophora. Grimaldi's classification of these taxa is quite different and places the Hawaiian Drosophila (Idiomyia) as sister group to the remaining ingroup taxa (Scaptomyza and the subgenera Sophophora and Drosophila). Our results show that Grimaldi's new classification of these taxa results in paraphyletic groups, just as does the traditional classification under Throckmorton's interpretation of relationships. Additional data are required to produce a robust classification of this huge paraphyletic genus. PMID- 8487636 TI - Mitochondrial DNA evolution in the Montium-species subgroup of Drosophila. AB - Mitochondrial DNA (mtDNA) restriction-site maps for six species (10 strains) of the Drosophila montium subgroup were established. A total of 50 restriction sites were mapped, corresponding to 1.67% of the mtDNA genome. On the basis of differences in the restriction sites, nucleotide divergence (delta) was calculated for each pair of species (strains), and phylogenetic trees were constructed by using distance-matrix and parsimony methods. Comparison of the resultant phylogenetic trees shows that the sibling species D. auraria and D. quadraria are closely related. At the other extreme, considerable divergence was observed between the two strains of D. serrata and between D. serrata and D. birchii, a finding that contrasts with their grouping within the same species complex. Nevertheless, our data indicate that these six oriental montium species are rather closely related. PMID- 8487637 TI - DNA insertions as a component of the evolution of unique satellite DNA families in two genera of parasitoid wasps: Diadromus and Eupelmus (Hymenoptera). AB - In the two parasitoid wasps, Diadromus collaris and Eupelmus orientalis, the satellite DNAs were each found to consist wholly or largely of a single family (5%-7% of the genome). Several clones of each family were obtained and sequenced. The repeat unit in each species is characterized by both the repetition of a basic motif and the presence of an inserted sequence. Sequence comparisons with satellite DNA from D. pulchellus and E. vuilleti provide plausible scenarios for the evolution of the satellite DNA in each genus. Palindromes and A-rich tracts in each consensus sequence suggest the formation, in vivo, of hairpin structures and bend centers that may play a role in heterochromatin condensation in insects. The insertions in the repeat units of each species also contain these structural features, suggesting that maintenance of these insertions requires constraints similar to those pertaining to the rest of the satellite-DNA unit. PMID- 8487638 TI - Low codon bias and high rates of synonymous substitution in Drosophila hydei and D. melanogaster histone genes. AB - We have evaluated codon usage bias in Drosophila histone genes and have obtained the nucleotide sequence of a 5,161-bp D. hydei histone gene repeat unit. This repeat contains genes for all five histone proteins (H1, H2a, H2b, H3, and H4) and differs from the previously reported one by a second EcoRI site. These D. hydei repeats have been aligned to each other and to the 5.0-kb (i.e., long) and 4.8-kb (i.e., short) histone repeat types from D. melanogaster. In each species, base composition at synonymous sites is similar to the average genomic composition and approaches that in the small intergenic spacers of the histone gene repeats. Accumulation of synonymous changes at synonymous sites after the species diverged is quite high. Both of these features are consistent with the relatively low codon usage bias observed in these genes when compared with other Drosophila genes. Thus, the generalization that abundantly expressed genes in Drosophila have high codon bias and low rates of silent substitution does not hold for the histone genes. PMID- 8487639 TI - Phylogenetic relationships among Taphrina, Saitoella, and other higher fungi. AB - To determine the phylogenetic placement of the major groups of higher fungi, we sequenced the DNA sequences from the small-subunit ribosomal RNA (18S rRNA) coding regions from Taphrina wiesneri (synonym: T. cerasi) and Saitoella complicata and compared them to 18S rRNA sequences from the oomycetes, chytridiomycetes, zygomycetes, ascomycetes, and basidiomycetes. Here we demonstrate that the ascomycetes have at least two major evolutionary lineages. Taphrina wiesneri and Saitoella complicata form a monophyletic branch that diverged prior to the separation of other ascomycetes. The same treatment could be accorded to Schizosaccharomyces pombe. PMID- 8487640 TI - The variability of the hepatitis B virus genome: statistical analysis and biological implications. AB - A statistical analysis of the nucleotide sequence variability in 14 published hepatitis B virus (HBV) genomes was carried out using parametric and nonparametric methods. A parametric statistical model revealed that the different regions of the genome differed significantly in their variability. The conclusion was supported by a nonparametric kernel-density model of the HBV genome. Genes S, C, and P, region X, the precore region, and the pre-S2/pre-S1 regions were ranked in order of increasing variability. In many instances, conserved regions of the genome identified with sequences of known function in HBV biology. However, other characterized regions (such as pre-S) showed much variability despite the involvement of their encoded peptides in specific functions. Point mutations that may result in the formation of stop codons and amino acid changes may affect the clinical picture of HBV infection and may be reflected in atypical serological patterns. PMID- 8487641 TI - Lack of mitochondrial DNA variation in Australian Drosophila buzzatii. PMID- 8487642 TI - The evolution of the cytochrome b protein: How many regions are conserved? PMID- 8487643 TI - Aldose reductase expression and prostaglandin E2 production are coordinately regulated in cultured rat mesangial cells. AB - There is increasing evidence that a link between the polyol pathway and prostaglandins is important in the pathogenesis of diabetic nephropathy. The presence of the polyol pathway in the kidneys of normal animals, the galactose fed rat, and animals with experimental diabetes has been established. While aldose reductase (AR) immunoreactive protein (AR-IRP) and AR mRNA are expressed at high levels in renal medulla, the sites of AR synthesis and regulation and metabolic consequences of AR activity in renal cortex are uncertain. The present study was conducted to test the hypothesis that AR expression and PGE2 production are coordinately regulated in glomerular mesangial cells. To test this hypothesis, we measured AR-IRP, AR mRNA, and PGE2 production in mesangial cells isolated from rats maintained on diets containing normal chow (MC-N), 50% galactose (MC-G), and 50% dextrin (MC-D). The rank order for each parameter studied (AR-IRP, AR mRNA, PGE2) was MC-N > MC-G > MC-D. Western blot analysis demonstrated that MC-N (optical density [OD] 1.0), MC-G (OD 0.59), and MC-D (OD 0.25) express AR-IRP. Slot-blot analyses demonstrated that levels of AR mRNA were greatest in MC-N (1.0), intermediate in MC-G (0.49), and lowest in MC-D (0.31). Ribonuclease (RNase) protection analyses demonstrated a similar pattern of AR mRNA expression, with MC-N at 1.0, MC-G at 0.60, and MC-D at 0.33. PGE2 production (pg/5 x 10(4) cells/30 min) was highest in MC-N (278 +/- 29), intermediate in MC-G (110 +/- 9), and lowest in MC-D (37 +/- 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487644 TI - Impaired glucose tolerance after endurance exercise is associated with reduced insulin secretion rather than altered insulin sensitivity. AB - Paired frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on five highly trained athletes within 2 hours of completing a 6-day ultramarathon run (E) and after 2 weeks of complete rest (R). Severe exercise increased free fatty acid (FFA) levels (E 1.2 +/- 0.16 v 0.42 +/- 0.07 mmol/L, P < .01) and norepinephrine levels (E 573 +/- 141 v 224 +/- 33 pg/mL, P < .01), with only moderate reductions in glucose tolerance (glucose disappearance [Kg] E 1.06 +/- 0.2 v R 1.7 +/- 0.3 min-1 x 10(2), P < .05). The minimal model analysis of FSIGT data using the method of Bergman et al (Endocr Rev 6:45-86, 1985) showed a reduced second-phase insulin secretion ([phi 2] E 5.2 +/- 1.3 v 13 +/- 2.2 microU/mL.min-2 per mg/dL, P < .05) and glucose disposition index ([SI x phi 2] E 33.8 +/- 10 v 73.9 +/- 11 mg-1.dL.min-3 x 10(4), P < .02). Insulin sensitivity (SI) and glucose-mediated glucose disposal (SG) were unchanged (SI E 6.9 +/- 1.0 v 6.0 +/- 0.6 min-1 per microU/mL x 10(4); SG E 1.8 +/- 0.6 v 1.4 +/- 0.3 min-1 x 10(2)). Reduced glucose tolerance after prolonged extreme physical exercise was accompanied by reduced phi 2 and not by alterations of SI or SG, despite the marked increase of FFA levels. Elevated norepinephrine levels, reflecting activation of the sympathetic noradrenergic system, was also associated with the reduction in Kg. The reduction in phi 2 would promote mobilization of FFA, the predominant metabolic substrate in these endurance events. PMID- 8487645 TI - Hepatic insulin action in adolescents with insulin-dependent diabetes mellitus: relationship with long-term glycemic control. AB - The relationship between hepatic insulin action and long-term glycemic control was assessed in 20 adolescents with insulin-dependent diabetes mellitus (IDDM) and five healthy matched controls using a two-step (0.8 and 1.6 mU/kg/min) hyperinsulinemic-euglycemic clamp and [6,6-2H2]glucose. The night before the study, diabetic patients received variable-rate intravenous insulin in an attempt to normalize fasting plasma glucose concentrations. In the postabsorptive state, hepatic glucose production (HGP) was similar in IDDM patients and controls (593 +/- 40 v 518 +/- 27 mumol/m2/min); however, plasma glucose and free insulin concentrations were higher in IDDM patients than in controls (6.5 +/- 0.4 v 5.4 +/- 0.1 mmol/L [P = .01], and 207 +/- 21 v 104 +/- 10 pmol/L [P < .001], respectively). There was a positive correlation (r = .62 P = .002) between basal HGP and glycohemoglobin level (HbA1). Separation of the patients at the median HbA1 (group no. 1 < and group no. 2. > 11.4% HbA1) revealed two distinct patient populations with regard to hepatic and peripheral insulin action and plasma free fatty acid (FFA) suppression. During hyperinsulinemia, the percent suppression of HGP was lower in group no. 2 compared with group no. 1 (65.7% +/- 9.8% v 94.4% +/ 3.8%; P = .018). Rates of glucose disposal were lower in group no. 2 compared with controls and with group no. 1. Postabsorptive FFA levels were similar between group no. 2 and group no. 1 (0.45 +/- 0.03 and 0.43 +/- 0.04 mmol/L) despite higher free-insulin concentrations in group no. 2 (260 +/- 30 v 171 +/- 25 pmol/L; P = .04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487646 TI - Protein turnover in advanced lung cancer patients. AB - Understanding the extent to which changes in whole-body protein kinetics contribute to the commonly observed weight loss and decrease in lean body mass (LBM) in patients with cancer is currently obscured by conflicting reports in the literature. While several studies have reported significant increases in whole body protein turnover (WBPT), synthesis (WBPS), and catabolism (WBPC) in patients with cancer, others have failed to confirm these observations. We have measured whole-body protein kinetics using a primed constant infusion of 15N-glycine in a homogenous group of 32 newly diagnosed advanced lung cancer patients with comparable staging and before any antineoplastic treatment, and in 19 normal healthy volunteer controls. Urinary urea and ammonia 15N enrichment was determined in individually collected urine samples obtained during the 24-hour study period and averaged for the determination of protein kinetics. During the last 6 hours of urine collection, samples were obtained hourly for determination of 15N plateau enrichment. Twenty-four-hour urinary nitrogen and creatinine excretion was determined from 24-hour pooled urine samples. Resting metabolic expenditure (RME) was determined by indirect calorimetry and LBM was estimated from deuterium oxide dilution. Age body weight, LBM, RME, and 24-hour urinary nitrogen excretion did not differ between cancer and control subjects. WBPT, WBPC, and WBPS (g/kg/d) were significantly increased in lung cancer patients. However, when the same results were expressed either per kilogram LBM or per gram 24-hour urinary creatinine excretion, WBPT, WBPC, and WBPS rates were not statistically different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487647 TI - Effects of tumor necrosis factor on the hypothalamic-pituitary-testicular axis in healthy men. AB - Tumor necrosis factor (TNF) has been implicated as a mediator of many diseases associated with alterations in hypothalamic-pituitary-testicular (HPT) function. To assess the effects of TNF on the HPT axis, we performed a saline-controlled cross-over study in six healthy men, sequentially measuring serum concentrations of gonadotropins, testosterone, and sex hormone-binding globulin (SHBG) after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced an early and transient increase in serum luteinizing hormone (LH) levels from 6.0 +/- 1.0 to a maximum of 8.0 +/- 1.0 U/L after 30 minutes (P < .005), whereas the concentrations of follicle-stimulating hormone (FSH) remained unchanged. The increase in LH concentrations was followed by a transient decrease in serum testosterone levels from 18.2 +/- 0.3 to 9.1 +/- 1.2 nmol/L after 4 hours (P < .0001). Remarkably, LH levels had returned to control values when the testosterone level reached its nadir. SHBG levels were not affected by TNF. Our results suggest that TNF affects the HPT axis at multiple levels and may be involved either directly or indirectly in the decrease in circulating testosterone concentrations in systemic illnesses. PMID- 8487648 TI - Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate. AB - The short-term administration of a nicotinic acid analogue (acipimox) increases insulin sensitivity and consequently glucose disposal, both in patients with non insulin-dependent diabetes mellitus (NIDDM) and in patients with cirrhosis. This effect has been attributed to a decrease in plasma nonesterified fatty acid (NEFA) levels and fatty acid oxidation rates, and a corresponding increase in carbohydrate oxidation. The aim of the present study was to determine whether acipimox influenced glucose disposal independent of changes in lipid metabolism. Seven normal men (age, 31 +/- 4 years; body mass index, 23.2 +/- 1.8 kg.m-2; fat free mass [FFM], 66.8 +/- 4.2 kg) were studied on two separate occasions with hyperinsulinemic (0.06 U.kg FFM-1.h-1) euglycemic clamps (duration, 150 minutes). A primed (150 U), continuous (0.4 U.kg-1.min-1) infusion of heparin together with 10% intralipid (25 mL.h-1) was infused in both studies from -90 to 150 minutes to maintain comparable levels of plasma NEFA and lipid oxidation rates. Acipimox (500-mg capsules) or placebo were administered orally in a double-blind random fashion at t = -90 and t = 0 minutes. Whole-body lipid and carbohydrate oxidation were measured in the last 30 minutes of both the basal (preclamp) period (-30 to 0 minutes) and the clamp period (120 to 150 minutes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487649 TI - The methylcobalamin metabolism of cultured human fibroblasts. AB - The effect of supplying exogenous methylcobalamin (MeCbl), a methyl donor to methionine synthase (MS), on the cellular metabolism of MeCbl was tested in cultured fibroblasts from healthy persons and from a subject with an inherited defect in the synthesis of MeCbl. MeCbl bound to transcobalamin II (TCII) was taken up in larger amounts than cyanocobalamin (CN-Cbl), but was equal to the uptake of hydroxocobalamin (OH-Cbl). The form of Cbl in the lysosomes persisted as the same form, bound to TCII, to which the cells were exposed in the medium. Once released from the lysosomes, both MeCbl and OH-Cbl were converted in the same proportions to coenzyme forms, suggesting equivalent entry into common cellular pools of Cbl from which active forms are synthesized. Exogenous MeCbl enjoyed no advantage in binding to MS, in synthesis of MeCbl, and in supporting cell division in the absence of methionine. All evidence supported the concept that in human cells the active MeCbl on MS forms de novo on the enzyme. It appeared unlikely that therapeutic MeCbl would have any advantage over OH-Cbl in the treatment of MeCbl deficiency or Cbl deficiency in general. PMID- 8487650 TI - Influence of omega-3 fatty acid treatment on cardiac phospholipid composition and coronary flow of streptozocin-diabetic rats. AB - Cardiac effects of omega-3 fatty acid treatment were studied in streptozocin (STZ)-induced (55 mg/kg intravenously [IV]) diabetic male Wistar rats. Nondiabetic control and STZ-diabetic animals were treated with Promega (0.5 mL/kg/d; Warner-Lambert, Morris Plains, NJ) for a period of 4 weeks beginning 2 weeks after either vehicle or STZ injection. Plasma glucose, triglyceride, and cholesterol concentrations were significantly (P < .05) elevated in diabetic animals; omega-3 fatty acid treatment did not significantly affect these parameters. An isolated working heart preparation was used to determine aortic and coronary flow rates in control, diabetic, treated control, and treated diabetic animals. Aortic and coronary flow rates of untreated STZ-diabetic rats were significantly (P < .05) lower than those of controls over a range of left atrial filling pressures (7.5 to 20 cm water). Both aortic and coronary flow rates of omega-3 fatty acid-treated diabetic animals were significantly (P < .05) increased above those of untreated diabetic rats. Aortic and coronary flow rates of treated diabetic rats paralleled those of control animals; omega-3 fatty acid treatment did not affect aortic or coronary flow rates of control animals. Cardiac phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and sarcoplasmic reticulum (SR) total phospholipid were isolated and the acyl composition was determined. Stearic acid and C22:4, n-6 were significantly reduced in cardiac PE of diabetic animals. Relative to PE acyl species of untreated nondiabetic controls, treated diabetic PE had increased eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA) and reduced C22:4, n-6 levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487651 TI - Treatment of E2E2 homozygous familial dysbetalipoproteinemic subjects with gemfibrozil does not enhance the binding of their d < 1.019 lipoprotein fraction to the low-density lipoprotein receptor. AB - Six E2E2 homozygous familial dysbetalipoproteinemic (FD) patients were treated with gemfibrozil (2 x 600 mg/d) for a period of 4 weeks. For all subjects, normalization of serum cholesterol concentrations with treatment did not result in a significant change in the cholesterol/triglyceride ratio of the d < 1.019 lipoprotein fraction. In addition, the binding efficiency of this lipoprotein fraction to the low-density lipoprotein (LDL) receptor on HepG2 cells did not change consistently with treatment. We conclude that normalization of serum cholesterol concentrations in FD patients by treatment with gemfibrozil is the result of an effect of gemfibrozil on the synthesis of d < 1.019 lipoproteins rather than an effect on the receptor-mediated clearance of these particles. PMID- 8487652 TI - Glucose turnover in severe falciparum malaria. AB - To investigate glucose metabolism in acute falciparum malaria, [3-3H]glucose turnover was measured in 18 normoglycemic adult Thais (eight males, 10 females; median age, 28 years) with severe infections. Eleven patients were studied before quinine treatment, 15 while receiving quinine, and 10 during convalescence. In paired studies conducted before and after initial intravenous quinine, plasma glucose level decreased from a median (95% confidence limits) of 5.5 (3.0 to 6.6) to 4.6 (2.5 to 6.1) mmol/L (P < or = .027, n = 8), and plasma insulin level increased 9.3 (-3.2 to 30.0) mU/L (P = .02). Glucose turnover decreased during the 4-hour quinine infusion from 3.04 (2.12 to 4.23) to 1.89 (1.20 to 2.54) mg/kg.min-1 (P < .004), as did the metabolic clearance rate for glucose (2.87 [1.88 to 7.83] to 2.50 [1.43 to 4.55) mL/kg.min-1; P = .008). Glucose turnover and clearance measured both after initial quinine treatment and in convalescence were similar (P = .234 and .344, respectively; n = 7). In the series as a whole, there was an inverse association between pretreatment turnover and the simultaneous plasma glucose level (rs = -.76, P < .01; n = 11), a stronger inverse relationship between glucose clearance and plasma glucose level (rs = .88, P < .001), and a positive association between pretreatment turnover and oral temperature (rs = .65, P < .025; n = 10). These data suggest that, as in other severe illnesses, glucose turnover is high in untreated patients, but that glycolysis by mature parasite forms may accelerate glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487653 TI - Effects of colonic fermentation on respiratory gas exchanges following a glucose load in man. AB - Colonic fermentation produces short-chain fatty acids (SCFA). In humans, the amount of energy produced from the oxidation of these compounds is unknown and could modify the metabolic utilization of energetic fuels (eg, carbohydrates and lipids). If it were so, the equations used to evaluate the oxidation of nutrients from indirect calorimetry data should include the contribution of SCFA, which is not usually the case. Indeed, this fermentation process is usually considered as a minor and neglected energetic pathway. In this study, we have addressed the reliability of this assumption. Six normal subjects received orally either 50 g glucose or 50 g glucose plus 20 g lactulose. Their respiratory gas exchanges, breath hydrogen, methane, and 13CO2 concentrations, and plasma glucose, insulin, and free fatty acid (FFA) concentrations were monitored for 8 hours. CO2 production and breath hydrogen concentration were significantly greater with lactulose. No differences in oxygen consumption, breath 13CO2 production, or plasma concentrations of blood glucose, FFA, and insulin could be found between the two experiments. This suggests that the fermentation process induced by lactulose generates extra fuels going through an oxidation pathway. Therefore, the classic equations used to calculate carbohydrate and lipid oxidation and energy expenditure (EE) from indirect calorimetry data are probably not valid when fermentation is taking place. Indeed, in this experiment we could have overestimated glucose oxidation (12.5%) if the fermentation process were not considered. In conclusion, colonic fermentation in humans of nondigestible carbohydrates produces energetic substrates that could be used and oxidized as energetic fuels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487654 TI - Effect of heparin on insulin-glucose interactions measured by the minimal model technique: implications for reproducibility using this method. AB - The minimal model technique permits investigation of glucose and insulin interactions during a frequently sampled intravenous glucose tolerance test (FSIGT). The model allows measurement of several important variables including insulin sensitivity (SI), glucose effectiveness at basal insulin (SG), and glucose effectiveness at zero insulin (GEZI). In addition, from the FSIGT, first phase insulin secretion (AIRglucose) and the glucose disappearance constant (Kg) can be estimated. The estimates obtained using the minimal model technique could be of importance in understanding potential relationships between carbohydrate and lipid metabolism. In studying lipoprotein lipase (LPL) activity and mass as one of the elements of lipid metabolism, heparin administration is necessary. However, the effect of administration of this agent on factors important in carbohydrate metabolism has not been fully elucidated. Therefore, to assess the effect of heparin on insulin-glucose interactions, we performed paired studies in which subjects randomly underwent FSIGT studies 20 minutes following bolus injections of heparin or saline. None of the measured parameters was influenced by heparin administration just before the FSIGT. Since these estimates were not affected by heparin administration, these studies also permitted assessment of the coefficient of variation of replicate analysis for all values generated using the minimal model technique. The coefficients of variation of replicate analysis calculated from these two studies were 16.9% for SI, 16.6% for SG, 18.3% for GEZI, 20.6% for AIRglucose, and 14.5% for Kg. These results suggest that heparin can be administered as part of a procedure that would allow concurrent assessment of various aspects of both carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487655 TI - Glutamine is a potentially limiting amino acid for milk production in dairy cows: a hypothesis. AB - Recently, extensive research has been focused on glutamine because of its key position between energy and protein metabolism. Evidence is growing that glutamine is essential in situations of metabolic stress; practical application of this knowledge can already be found in parenteral nutrition of severely ill patients. Furthermore, glutamine is claimed to increase muscle protein synthesis. Glutamine and its counterpart, glutamic acid, are the most abundant amino acids in milk protein. Nevertheless, the role of nonessential amino acids (NEAA) in milk protein synthesis in high-yielding dairy cows has been practically neglected during the past 20 years. Evaluating current literature on glutamine metabolism in ruminants with emphasis on data related to milk protein production, we conclude the following: (1) Ruminants have a relatively low glutamine synthetase capacity compared with monogastric species, reflected in relatively low plasma glutamine levels; (2) The uptake of glutamine by the mammary gland is effectively 100% of the arterial supply; (3) Milk production in high-yielding dairy cows represents a metabolic stress comparable to fasting or acidosis; and (4) Responses of plasma and tissue glutamine pools in conditions of "metabolic stress," including high milk production, resemble those of most essential amino acids (EAA). Therefore we hypothesize that glutamine, although regarded as a NEAA, limits milk protein synthesis in high-yielding dairy cows. PMID- 8487656 TI - No change in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet. AB - Possible changes in glucose tolerance and substrate oxidation after a high carbohydrate, low-fat diet were studied in seven healthy volunteers. Each subject consumed two experimental diets for 1 week after 1 week on a stabilization diet; diet no. 1 11% fat and 64% carbohydrates, and diet no. 2 30% fat and 45% carbohydrates. At the end of each experimental week, plasma levels of glucose, insulin, and free fatty acids were measured before and every 30 minutes for 6 hours after a 75-g oral glucose challenge. At the same time, energy expenditure and substrate oxidation were measured by indirect calorimetry. Plasma lipid and lipoprotein levels were measured at the end of one stabilization period and at the end of each diet. Plasma glucose concentrations and areas under the curve of glucose concentrations were identical after the two experimental periods; the means +/- standard deviation for the values at 120 minutes were 6.4 +/- 0.3 and 6.4 +/- 0.6 mmol/L after diets no. 1 and 2, respectively, and areas under the curve were 1,853 +/- 115 and 1,862 +/- 211 mmol.min/L after diets no. 1 and 2, respectively. Similarly, plasma concentrations of insulin and free fatty acids after glucose ingestion were unaffected by the dietary changes. Energy expenditure increased after glucose administration, and this thermic effect of glucose was identical after the two experimental diets at 4.2% +/- 1.4%, and 3.9% +/- 1.4% of ingested energy for diets no. 1 and 2, respectively. Substrate oxidation rates were also identical for both the fasted and post-glucose periods after the two diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487657 TI - Lack of insulin feedback inhibition in non-obese and obese men. AB - The existence of insulin feedback inhibition is a controversial issue. The present study adopted a novel approach to determine whether insulin feedback inhibition exists in vivo during physiologic hyperinsulinemia and if it could contribute to enhanced insulin secretion in obesity. Serial plasma insulin and C peptide levels were determined during a basal state and a hyperinsulinemic clamp (287 pmol/min/m2) and following discontinuation of the insulin infusion under euglycemic conditions. Insulin secretion rates were derived from plasma C-peptide levels and individual C-peptide kinetics using a two-compartment model. Eight non obese and nine obese men were recruited for the studies, which were performed in random order. Men with significant variations in glucose levels during hyperinsulinemia were excluded from the analysis. Plasma glucose levels were similar between the non-obese and obese groups during all phases of the study, and similar plasma insulin levels were achieved in both groups during euglycemic hyperinsulinemia. In obese men, C-peptide levels were significantly greater compared with non-obese men during euglycemic hyperinsulinemia (P < .05). However, neither the non-obese nor the obese group demonstrated significant suppression of insulin secretion rates during euglycemic hyperinsulinemia. Expressing the data in absolute terms or as a percent of basal did not alter the results. Moreover, there was no significant change between the non-obese and the obese group during the rapid onset and cessation of hyperinsulinemia. Under euglycemic conditions, physiologic hyperinsulinemia does not induce suppression of endogenous insulin secretion in non-obese or obese men. PMID- 8487658 TI - Influence of calmodulin antagonists and calcium channel blockers on triiodothyronine uptake by rat hepatoma and myoblast cell lines. AB - The influence of calcium-related mechanisms on cellular uptake of triiodothyronine (T3) has not yet been defined, although it is known that T3 can stimulate cellular entry of calcium. We therefore investigated the saturable uptake of [125I]-T3 (10(-11) mol/L) from serum-free medium in vitro by hepatoma (H4) cells and skeletal myoblast (L6) cells to establish the calcium-dependency of this process. We studied the effects of the following three structurally distinct types of calmodulin antagonists in H4 cells: the naphthalene sulfonamides W7, W12, and W13, calmidazolium, and trifluoperazine. Uptake of [125I]-T3 as a percentage of control values (n = 4, 10(-4) mol/L antagonist) was as follows: W7, 42.0% +/- 3.3% (P < .001); W12, 87.5% +/- 4.5% (NS); W13, 79.5% +/- 2.5% (P < .05); calmidazolium (10(-6) mol/L, n = 8), 55.1% +/- 2.2% (P < .001); and trifluoperazine (10(-5) mol/L, n = 6), 65.7% +/- 4.1% (P < .001). To investigate whether the calmodulin sensitivity of uptake was mediated via transmembrane calcium flux, we also studied the effects of three structurally distinct types of organic calcium channel blockers in both H4 and L6 cells. [125I]-T3 uptake as a percent of control values (10(-4) mol/L blocker, n = 4) was as follows: nifedipine, 8.6% +/- 0.9% (H4) and 16.7% +/- 7.2% (L6); verapamil, 24.6% +/- 3.2% (H4) and 61.9% +/- 4.2% (L6); diltiazem, 62.7% +/- 3.6% (H4) and 36.1% +/- 5.4% (L6); all P < .001. Eadie-Hofstee analysis indicated competitive inhibition of T3 uptake for both calmidazolium and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487659 TI - Apolipoprotein E polymorphism and its association with serum lipoprotein concentrations in black versus white children: the Bogalusa Heart Study. AB - The structural gene locus for apolipoprotein E (apo E) is polymorphic. The relative apo E allele frequencies and the influence of this polymorphism on serum lipoprotein concentrations were studied in 8- to 17-year-old black (n = 444) and white (n = 446) children from the community of Bogalusa, LA. The frequencies of the e2, e3, and e4 alleles for white males/females were 0.027/0.024, 0.849/0.823, and 0.124/0.153, respectively; corresponding values for black males/females were 0.087/0.074, 0.713/0.721, and 0.20/0.205, respectively. Apo E phenotype distributions and allele frequencies showed a significant race difference, but no sex difference. Significant differences among apo E phenotypes were noted for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apo B in both races; significant effects were noted for high-density lipoprotein cholesterol (HDL-C) and apo A-I in black children, but not in white children. Among white children, the average excess of the apo e2 allele showed lower LDL-C (-12.5 mg/dL) and apo B (-15.8 mg/dL) concentrations, while the average excess of the apo e4 allele showed higher LDL-C (7.0 mg/dL) and apo B (7.5 mg/dL) concentrations. Black children showed a similar trend for these variables, but to a lesser degree; in addition, the average excess of apo e2 allele showed higher HDL-C (12.8 mg/dL) and apo A-I (8.3 mg/dL) concentrations in this racial group. It is noteworthy that the association of apo E polymorphism with serum lipoprotein concentrations noted in adults can be seen already in children. PMID- 8487660 TI - Effect of prolonged hyperglycemia on growth hormone levels and insulin sensitivity in insulin-dependent diabetes mellitus. AB - The aim of the present study was to characterize the effect of a hyperglycemic period (44 hours) on the levels of insulin-antagonistic hormones and insulin sensitivity in seven subjects with well-controlled insulin-dependent diabetes mellitus (IDDM). Hyperglycemia (approximately 15 mmol.L-1) was induced by a glucose infusion while the degree of insulinization was similar to that of the period with near normoglycemia (approximately 6.9 mmol.L-1). Insulin sensitivity was measured with hyperinsulinemic euglycemic clamps performed 4 hours before and after the periods of normoglycemia (control) and hyperglycemia. D-[3-3H]glucose was infused in the second clamp in each study to evaluate glucose production and utilization. Since growth hormone (GH) levels frequently are elevated during poor diabetic control, diurnal GH secretion was measured in blood samples continuously drawn for 24 hours during the euglycemic and hyperglycemic periods. Levels of epinephrine, norepinephrine, cortisol, and nonesterified free fatty acids (NEFA) were similar during the control and hyperglycemic periods and during the clamps. GH levels were also similar, but an abnormal diurnal secretion pattern was present with increased numbers of daytime peaks. Hyperglycemia did not reduce GH secretion in IDDM. Hyperglycemia for 44 hours induced insulin resistance (32% reduction of glucose infusion rate, P < .02). In the control study, a 21% reduction (P = .064, NS) of the glucose disposal rate (Rd) was seen, suggesting that the hospitalization period per se may also reduce insulin sensitivity. In conclusion, a period of hyperglycemia leads to insulin resistance in IDDM patients. This insulin resistance cannot be attributable to increased levels of insulin-antagonistic hormones, although an abnormal secretion pattern for GH was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487661 TI - Sodium ipodate and methimazole in the long-term treatment of hyperthyroid Graves' disease. AB - A prospective study was conducted to evaluate the effect of prolonged treatment of hyperthryoid Graves' disease with methimazole (MMI) for 12 months or Na ipodate for only 6.6 +/- 1.1 months, since the drug had to be discontinued because of persistent or recurrent hyperthyroidism during treatment. The eight patients who were treated with MMI alone for 12 months became euthyroid, and seven remained in remission for at least 6 months after MMI was discontinued. In contrast, only two of 10 patients treated with Na ipodate alone became euthyroid and remained so during therapy. No ipodate was discontinued in the eight patients who did not respond, and they were then treated with MMI. One patient had recurrent hyperthyrodism after NA ipodate was discontinued, and she was then treated with MMI. MMI was efficacious in treating these nine patients, and all patients were euthyroid by the third month of MMI administration. Five of these nine patients remained euthyroid for at least 6 months after MMI was discontinued, a remission rate that was not significantly different from that observed in the eight patients treated only and initially with MMI (Fisher's Exact Test). There was no significant change in serum thyroid peroxidase antibodies during treatment with MMI alone, Na ipodate alone, or Na ipodate followed by MMI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487662 TI - Effects of chloroquine on the dyslipidemia of non-insulin-dependent diabetes mellitus. AB - The effects of 3-day oral chloroquine phosphate treatment administered at a dosage of 250 mg four times daily on fasting serum levels of lipids, lipoproteins, and apolipoproteins were studied in 20 patients with non-insulin dependent diabetes mellitus (NIDDM). Chloroquine reduced the fasting serum concentrations of total cholesterol (6.16 +/- 0.31 to 5.67 +/- 0.31 mmol/L, P < .05), low-density lipoprotein (LDL) cholesterol (4.38 +/- 0.35 to 3.93 +/- 0.32 mmol/L, P < .05), and apolipoprotein (apo) B (1.46 +/- 0.08 to 1.24 +/- 0.06 g/L, P < .01), and the ratio of apo B to apo A-I (0.81 +/- 0.05 to 0.71 +/- 0.03, P < .05). Chloroquine also caused a decrease in fasting plasma glucose levels (11.1 +/- 0.5 to 9.2 +/- 0.4 mmol/L, P < .01) and an increase in fasting plasma insulin levels (0.12 +/- 0.01 to 0.14 +/- 0.01 nmol/L, P < .01). The decrease in total cholesterol and apo B levels correlated with the increase in fasting plasma insulin levels (r = .35, P = .04 and r = .33, P = .03, respectively), but not with changes in plasma levels of glucose or nonesterified fatty acids (NEFA). This study demonstrates that 3 days of oral chloroquine treatment improves abnormalities of lipoprotein metabolism in patients with NIDDM. This may be due to an increase in insulin levels, but there also appears to be a more direct effect of the drug on apo B metabolism. PMID- 8487663 TI - Differential effect of aging on protein kinase C activity in rat adipocytes and soleus muscle. AB - Protein kinase C (PKC) has been postulated to play an important role in glucose transport in insulin-sensitive tissues such as rat adipocytes and skeletal muscle. Since glucose transport decreases in old rats, we examined age-related changes in PKC. Cytosolic PKC-dependent histone-phosphorylating enzyme activity and PKC-beta immunoreactivity of both adipocytes and soleus muscles increased progressively with age (or weight) in rats weighing less than 400 g. In comparing PKC enzyme activity and PKC-beta immunoreactivity in young rats (180 +/- 32 g; mean +/- SE, body weight) versus old rats (658 +/- 108 g), both cytosolic and membrane-associated PKC were greater in adipocytes of old rats (relative to adipocytes of young rats), whereas in the soleus muscle of old rats cytosolic PKC activity was diminished and membrane-associated PKC was increased (relative to solei of young rats). The latter redistribution of soleus PKC may be due to endogenous hyperinsulinemia, which is known to occur in old rats and which may have stimulated the translocation of PKC from cytosol to membrane in the soleus. Whatever the cause, decreases in cytosolic PKC in the soleus muscle may limit acute PKC translocation responses to insulin or other agents in old rats. PMID- 8487664 TI - The effects of changes in plasma nonesterified fatty acid levels on oxidative metabolism during moderate exercise in patients with non-insulin-dependent diabetes mellitus. AB - Blood levels of intermediary metabolites were measured and indirect calorimetry was performed in 10 otherwise healthy, non-insulin-dependent diabetic (NIDDM) patients before, during, and after 30 minutes of moderate exercise on three occasions in random order at weekly intervals with (1) heparin treatment to increase preexercise plasma nonesterified fatty acid (NEFA) levels (HEPARIN); (2) acipimox, a nicotinic acid analogue, to reduce preexercise plasma NEFA levels (ACIPIMOX); and (3) no manipulation of preexercise plasma NEFA levels (NIL). With ACIPIMOX, preexercise blood levels were significantly reduced for NEFAs and glycerol (P < .01) and marginally reduced for acetoacetate and 3-hydroxybutyrate (NS) compared with preexercise levels for the other two treatments; these low levels seen with acipimox treatment increased only slightly during exercise and the postexercise period. Plasma NEFA levels increased by approximately 150% (P < .001) with HEPARIN at the same times. The levels of ketone bodies during either NIL or HEPARIN increased rapidly postexercise by approximately 90% to 110% for both acetoacetate and 3-hydroxybutyrate (both P < .01). Plasma insulin levels tended to be lowest (despite similar plasma glucose levels during the three treatments) with ACIPIMOX, while growth hormone (hGH) and, perhaps, noradrenaline levels were highest both during and after exercise. The respiratory quotient (RQ) was highest with ACIPIMOX (P < .05 for exercise and postexercise periods compared with the other two treatments), which, compared with NIL, reduced fat oxidation by 27% and 60% and increased carbohydrate oxidation by 29% and 74% during and after exercise, respectively (all P < .05). These changes in substrate oxidation due to ACIPIMOX were almost opposite to those observed with HEPARIN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487665 TI - Regulation of contraction-stimulated system A amino acid uptake in skeletal muscle: role of vicinal sulfhydryls. AB - Functional vicinal sulfhydryls are essential for insulin-stimulated system A neutral amino acid uptake in the rat epitrochlearis muscle. In skeletal muscle, system A uptake is also activated by contractile activity. Therefore, the purposes of this study were to characterize the stimulation of system A activity by contractions induced by electrical stimulation in vitro, and to assess the role of vicinal sulfhydryls in this process. System A activity in the isolated epitrochlearis muscle was measured using the nonmetabolizable analogue alpha (methylamino)isobutyric acid (MeAIB). Contractions increased MeAIB uptake by increasing the apparent maximal velocity (Vmax), with no alteration in the apparent Km. The maximal stimulatory effects of insulin and contractions on MeAIB uptake were completely additive, demonstrating that these two stimuli exert their effects via different mechanisms. Phenylarsine oxide (PAO), a vicinal sulfhydryl antagonist, at greater than 20 mumol/L inhibited basal and contraction-stimulated MeAIB uptake by approximately 50% and 70%, respectively, by decreasing Vmax, with no change in Km. Both inhibitory effects were completely prevented by cotreatment with the vicinal dithiol dimercaptopropanol (DMP), indicating the effects were mediated by interactions with vicinal sulfhydryls. Contraction-stimulated MeAIB uptake was rapidly (half-time, approximately 7 minutes) reversed by the addition of PAO. These results (1) define conditions under which contraction-stimulated system A amino acid uptake can be studied in an isolated mammalian skeletal muscle preparation, and (2) indicate that vicinal sulfhydryls are essential for stimulation of system A activity by muscle contractions. PMID- 8487666 TI - The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity. AB - Stanozolol, an oral 17 alpha-alkylated androgen, increases hepatic triglyceride lipase activity (HTGLA) and decreases high-density lipoprotein cholesterol (HDL C) levels, whereas intramuscular testosterone has comparatively little effect. In the present study, we tested the hypothesis that aromatization of androgen to estrogen blunts the lipid and lipase effects of exogenous testosterone. Fourteen male weightlifters received testosterone enanthate (200 mg/wk intramuscularly), the aromatase inhibitor testolactone (250 mg four times per day), or both drugs together in a randomized cross-over design. Serum testosterone level increased during all three drug treatments, whereas estradiol level increased only with testosterone alone (+47%, P < .05), demonstrating that testolactone effectively inhibited testosterone aromatization. Testosterone decreased HDL-C(-16%, P < .05), HDL2-C(-23%, NS), and apoprotein (apo) A-I (-12%, P < .05) levels, effects that were consistently but not significantly greater with simultaneous testosterone and testolactone administration (HDL-C, -20%; HDL2-C, -30%; apo A-I, -15%; P < .05 for all). In contrast, both testosterone regimens decreased HDL3-C levels by 13% (P < .05 for both). HTGLA increased 21% during testosterone treatment and 38% during combined testosterone and testolactone treatment (P < .01 for both). Lipoprotein lipase activity (LPLA) increased only during combined testosterone and testolactone treatment (+31%, P < .01), suggesting that estrogen production may counteract the effects of testosterone on LPLA. Testolactone alone had little effect on any lipid, lipoprotein, apoprotein, or lipase concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487667 TI - Skeletal muscle lipids and glycogen mask substrate competition (Randle cycle). AB - The glucose-free fatty acid (FFA) cycle (Randle) was examined in soleus muscle, a red muscle with a high lipid oxidation rate, and extensor digitorum longus (EDL) muscle, a white muscle with a low lipid oxidation rate, using a carnitine palmethyltransferase (CPT-I) inhibitor as a probe. Exogenous palmitate by itself had little if any effect on glycolysis or glycogen accumulation in the two muscle types. The CPT-I inhibitor markedly decreased glycogen accumulation in both muscles (from fed rats), but increased glycolysis (lactate formation) and glucose oxidation to carbon dioxide only in the red muscle. When the muscles were made more dependent on FFA oxidation by prior fasting or exercise, the CPT-I stimulatory effect on glycolysis and glucose oxidation in white muscle was unmasked. In conclusion, the competition between lipid and carbohydrate utilization (Randle cycle) is easily demonstrated in both red and white muscle using a CPT-I inhibitor as a probe. The difficulties encountered in showing this competition in other studies using exogenous FFA may be explained by a combination of factors, including (1) low tissue lipid oxidation rates, (2) competition between exogenous and endogenous lipids such that provision of exogenous lipids fails to increase overall lipid oxidation, and (3) preferential utilization of exogenous glucose with glycogen sparing in the presence of FFA. PMID- 8487668 TI - Measuring glucose and fructose-6-phosphate cycling in liver in vivo. AB - Approaches measuring futile cycling of glucose and fructose-6-phosphate (fructose 6-P) in liver in vivo depend on assumptions about the fates of hydrogens bound to specific carbons of glucose. Thus, 3H of [2-3H]glucose has been assumed to be completely removed after its conversion to glucose-6-P, [3-3H]glucose after its conversion to fructose-1,6-bisP, and [6-3H]glucose not at all. Previous measurements have shown that these assumptions are incompletely fulfilled. Corrections to estimates of cycling can be made when detritiations of [2 3H]glucose and [3-3H]glucose are not complete, and detritiation of [6-3H]glucose occurs. How the corrections can be made is presented using data previously reported on giving labeled glucoses to humans after an overnight fast and on infusing a glucose load. Estimates of glucose cycling nearly double, and that of fructose-6-P cycling almost triples. Estimates of hepatic glucose production as measured with [6-3H]glucose decrease. Correction of estimates of cycling under other conditions may very well be similarly affected. Thus, rates of glucose and fructose-6-P cycling appear to be substantially more than previously estimated. Quantitation under a given condition requires measurements to be made of the extent to which assumptions as to the fate of labeled hydrogen of the glucoses are fulfilled. The uncertain extent of exchange of label catalyzed by transaldolase and detritiation in the pentose cycle, the failure of fructose-6-P cycling to be expressed through detritiation of 3H from [3-3H]glucose, and possible isotope effects still limit the confidence that can be placed in such estimates. PMID- 8487669 TI - Comparison of the effects of diets rich in stearic acid versus myristic acid and lauric acid on platelet fatty acids and excretion of thromboxane A2 and PGI2 metabolites in healthy young men. AB - The present study compared the effects of diets rich in stearic acid (C18:0) versus one high in lauric and myristic acid (C12:0, C14:0) on platelet phospholipid fatty acid levels and concentrations of urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and PGI2 and indicators of cardiovascular hemostasis. A diet high in dairy butter (B) was the source of C12:0 and C14:0; C18:0 was provided by diets high in cocoa butter (CB), milk chocolate (CHOC) or CB+B in a 4:1 ratio (MIX). A randomized, crossover double-blind experimental design was used. Experimental subjects (n = 15) consumed each diet for 26 days, with a 1-month washout period between each experimental period. Urine and blood were collected from each subject at the beginning and end of each dietary period. Urinary TXB2 and 6-keto PGF1 alpha were analyzed by radioimmunoassay (RIA). There were no effects of diet on the 24-hour excretion of either metabolite or on the ratio of 6-keto-PGF1 alpha/TXB2, even though there were significant changes in the eicosanoid precursor, arachidonic acid (C20:4n-6), in platelet phospholipids. C20:4n-6 levels increased (44.8% +/- 1.0% to 47.1% +/- 1.3%; P < .05) in the phosphatidylethanolamine phospholipid subclass in subjects on the B diet and decreased in the phosphatidylcholine subclass on the CB diet (16.5% +/- 1.0% to 14.2% +/- 1.1%; P < .05) compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487670 TI - Effect of uremia on aldosterone metabolism in the isolated perfused rat liver. AB - The effect of uremia on hepatic metabolism of aldosterone was studied in the isolated perfused liver of female Wistar rats. Uremia was induced by five-sixths partial nephrectomy 4 weeks before experiments. Isolated livers of normal and uremic rats were perfused at a constant flow rate with a hemoglobin-free medium, to which 4-14C-D-aldosterone was added at 3 nmol/L. Aldosterone was analyzed by radioimmunoassay (RIA) and 4-14C-D-aldosterone radiometabolites in perfusate and bile were assayed by high-performance liquid chromatography (HPLC). Uremic rats had a 10% lower body weight (P < .01) and increased plasma urea, creatinine, and parathyroid hormone (PTH) levels (258%, 200%, and 208%, respectively; P < .01 .001). Blood pressure and plasma K+, Na+, and aldosterone levels were similar. Plasma renin activity was suppressed by 68% in uremic rats (P < .001). Liver wet weight and hepatic function were similar in livers of both groups of rats. Hepatic elimination of aldosterone was compatible with a first-order kinetics. Hepatic clearance of aldosterone per liver and per gram liver was similar; however, when expressed per 100 g rat body weight, a 21% higher value was observed in uremic rats (11.6 +/- 1.8 mL/min) compared with normal rats (9.6 +/- 1.5 mL/min, P < .01). Polar aldosterone radiometabolites accumulated in the perfusate to approximately 40% of the initial 14C added at 15 minutes, and were eliminated in bile at a similar rate in both groups. No qualitative difference was found in the pattern of radiometabolites of aldosterone in perfusate and bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487671 TI - Insulin binding and degradation by rat liver Kupffer and endothelial cells. AB - The liver is the major site of insulin metabolism. Previous studies have suggested that hepatocytes were chiefly responsible for this activity, while contributions of Kupffer and other nonparenchymal liver cells remained controversial. In this study, we compared 125I-insulin binding and degradation by rat hepatocytes with insulin binding and degradation by sinusoidal Kupffer and endothelial cells. Kupffer cells were separated from endothelial cells by centrifugal elutriation. Hepatocytes had approximately 3.5 times more insulin binding sites than Kupffer cells and approximately eight times more binding sites than endothelial cells. In addition, wheat germ agglutinin (WGA)-purified solubilized receptors from all three cell types bound insulin in proportions similar to whole cells. Moreover, all three cell types were shown with a ribonuclease (RNase) protection assay to express insulin receptor mRNA. Hepatocytes degraded approximately four times more insulin than Kupffer cells, while endothelial cells degraded only negligible amounts of insulin. Based on morphometric data available in the literature, we estimated that nonparenchymal cells could account for approximately 10% to 15% of hepatic insulin degradation. We concluded that rat hepatocytes, Kupffer cells, and endothelial cells all have specific insulin receptors, and that nonparenchymal cells play a small but significant role in insulin degradation. PMID- 8487672 TI - Prospective evaluation of beta-cell function in insulin autoantibody-positive relatives of insulin-dependent diabetic patients. AB - During the preclinical period of insulin-dependent diabetes mellitus (IDDM), progression to clinical IDDM is characterized by declining beta-cell function. Although the presence of insulin autoantibodies (IAA) improves the ability of islet cell antibodies (ICA) to predict subsequent clinical IDDM, few studies have examined the risk of developing IDDM in subjects positive for IAA but negative for both ICA and antibodies to glutamic acid decarboxylase (64kA). To investigate this question, detailed beta-cell function tests (acute insulin response to glucose [AIRgluc] and slope of glucose potentiation) were performed on eight IAA positive first-degree relatives of insulin-dependent diabetics. All eight subjects were negative for ICA, and seven were tested for 64kA and were negative. Five subjects were studied prospectively for 22.4 +/- 9.4 months, while three subjects had only initial studies. Initial beta-cell function tests were normal in each subject. AIRgluc was 122.2% +/- 19.0% of the expected normal response, while slope was 168.6% +/- 20.6% of expected normal response. beta-cell function remained normal and remarkably stable in the five subjects followed prospectively. AIRgluc did not significantly change from an initial value of 147.9% +/- 23.1% of expected to 153.2% +/- 22.4% (NS). The slope of glucose potentiation varied little from 165.5% +/- 39.4% initially to 159.5% +/- 27.3% (NS) at the most recent determination. We conclude that among nondiabetic first degree relatives of IDDM subjects, the presence of IAA in the absence of ICA and 64kA is not usually associated with and therefore does not reliably predict beta cell dysfunction or progressive deterioration in beta-cell function. PMID- 8487673 TI - Variation in total energy expenditure in young healthy free-living men. AB - Interindividual and intraindividual variation in total energy expenditure (TEE) were examined in 17 healthy, free-living men (weight, 56.4 to 82.4 kg; age, 18 to 30 years). TEE over 14 days, resting metabolic rate (RMR), and body composition were measured two or three times during 77 days of fixed caloric intake using doubly labeled water, respiratory gas analysis, and isotope dilution, respectively. When individual data were averaged, TEE was most significantly related to fat-free mass ([FFM] r = .73, P = .001), body mass (r = .70, P = .002), and RMR (r = .63, P = .006). After adjusting TEE for BM, a significant inverse relation with age was found (partial r = -.52, P = .032). Stepwise regression analysis showed that 69% of individual variation in TEE was explained by BM, age, and fasting respiratory exchange ratio (RER). TEE/RMR averaged 1.73 +/- 0.25 (range, 1.38 to 2.32), and was independent of age and body composition. In 10 subjects in whom triplicate observations of TEE were performed, the average experimental variation for TEE was +/- 11.9% (range, 6.1% to 19.6%) compared with a theoretical estimate of precision of +/- 5.9% based on the reported isotope dose and analytical uncertainty. The difference between theoretical estimates of precision and observed experimental variation suggests that inherent random variation in free-living TEE is +/- 10% (ie, square root of 12(2)-6(2)) in subjects maintained on fixed caloric intake. We conclude that in young free living men (1) BM, age, and RER are important determinants of TEE; and (2) intraindividual variation in TEE is approximately +/- 10% due to fluctuations in physical activity levels within individuals over time. PMID- 8487674 TI - Simvastatin improves chylomicron remnant removal in familial combined hyperlipidemia without changing chylomicron conversion. AB - It is unknown whether the clearance of atherogenic chylomicron remnants and the postprandial lipoprotein metabolism in general can be improved by 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in subjects with familial combined hyperlipidemia (FCH). Therefore, the postprandial chylomicron remnant clearance was studied in nine normolipidemic untreated controls and seven FCH patients before and after treatment with simvastatin using an oral vitamin A fat load (24 hours, 50 g/m2). Treatment with simvastatin reduced plasma cholesterol level by 16% (mean +/- SEM, 8.1 +/- 0.8 v 6.8 +/- 0.8 mmol/L; P < .05) and plasma apolipoprotein (apo) B level by 19% (1.6 +/- 0.2 v 1.3 +/- 0.2 g/L; P < .05). Plasma apo E level (89.6 +/- 21.0 mg/L) was reduced by 29% (63.5 +/- 14.1 mg/L; P < .05). High-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels did not change; consequently, the reductions seen had been due to a decrease in very-low-density lipoprotein (VLDL) levels. Fasting plasma triglyceride (30% reduction) and plasma apo C-II (31% reduction) levels did not change significantly. Mean postheparin plasma lipoprotein lipase (LPL) activity increased by 13% after treatment (90.4 +/- 19.8 v 102.6 +/- 20.3 mU/mL; P < .05), but hepatic lipase (HL) activity was not altered. The clearance of chylomicrons (Sf > 1,000), expressed as the area under the 24-hour retinyl palmitate curve, did not change with simvastatin (52.8 +/- 12.9 v 51.8 +/- 13.4 h.mg-1/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487675 TI - Periprandial regulation of lipid metabolism in insulin-treated diabetes mellitus. AB - We have examined the regulation of lipid and glucose metabolism in the postabsorptive and postprandial states in six subjects with insulin-treated diabetes mellitus, and compared them with eight nondiabetic subjects. Blood or plasma concentrations of metabolites and fluxes across forearm and subcutaneous adipose tissue were studied after an overnight fast and for 6 hours after a mixed meal (3.1 MJ, 41% from fat). In the postabsorptive state, regulation of lipid metabolism in the two groups appeared basically similar except that a wider spread of plasma (free) insulin concentrations in the diabetic group led to a wider range of values of plasma nonesterified fatty acid (NEFA) release from adipose tissue, plasma NEFA concentrations, and blood ketone body concentrations. Extraction of ketone bodies across adipose tissue was positively correlated with arterial concentration in both groups (as it was in the forearm), confirming the ability of human adipose tissue to utilize ketone bodies. A single subcutaneous injection of insulin before the meal in the diabetic group produced a plasma free insulin profile that was blunted and prolonged compared with the postprandial response in the control group. Postprandial forearm glucose uptake followed very closely the plasma (free) insulin concentration. Postprandial suppression of NEFA release from adipose tissue was essentially normal in the diabetic group, and the normal postprandial decrease in plasma NEFA concentrations was reproduced extremely closely. Forearm and adipose tissue blood flow did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487676 TI - Pituitary-testicular and pituitary-thyroid axes in spinal cord-injured males. AB - Thirty spinal cord-injured (SCI) males were studied for evaluation of their pituitary-testicular and pituitary-thyroid axes using combined luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) tests and electroejaculated semen analyses. Thirty age-matched normal male volunteers served as controls. There were four subjects with low serum triiodothyronine (T3) levels, one with elevated serum follicle-stimulating hormone (FSH) level, eight with elevated serum testosterone levels, and 11 with elevated serum prolactin levels. There were significantly elevated luteinizing hormone (LH) responses to LHRH in SCI subjects when compared with normal controls. There were 16 (53.3%) SCI subjects who had exaggerated and/or prolonged LH responses. Among them, six subjects also had elevated FSH responses. There were eight and four subjects whose thyrotropin (TSH) and prolactin responses to TRH were exaggerated, respectively. Marked impaired motility was observed in 56 electroejaculated semen samples from 16 SCI subjects. There was a significant correlation between LH and total sperm count. Our data suggest that there is a reduced central dopaminergic tone in SCI subjects. PMID- 8487677 TI - Glucose fluxes and oxidation after an oral glucose load in patients with non insulin-dependent diabetes mellitus of variable severity. AB - The relative contribution of liver and peripheral tissues to the postprandial glucose response has been examined in 19 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 11 matched nondiabetic control subjects during a 5 hour oral glucose tolerance test (OGTT) performed with a load of 75 g, corresponding to approximately 67 g/1.73 m2. A dual-tracer technique was used to measure exogenous and endogenous glucose fluxes separately. Glucose oxidation was measured by indirect calorimetry. Diabetic patients were subdivided into two subgroups designated as "mild" (n = 7) and "severe" (n = 12) NIDDM according to postabsorptive glucose concentration with a cut-off point of 140 mg/dL. In the basal state, glucose concentrations averaged 99, 117, and 194 mg/dL, respectively, in control subjects and in the two diabetic subgroups, but insulin concentrations were not significantly different between groups. In comparison to control subjects, the basal hyperglycemia of mildly diabetic patients was entirely caused by a reduced metabolic clearance rate (118 v 144 mL/min; P < .05), whereas in severely diabetic patients basal hyperglycemia resulted from a combination of increased hepatic glucose output (187 v 139 mg/min; P < .001) and decreased metabolic clearance rate (97 v 144 mL/min; P < .001). A similar situation prevailed during the initial 2 hours after glucose ingestion. In patients with mild NIDDM, glucose concentration increased by 121 +/- 10 mg/dL as compared with 36 +/- 7 mg/dL in control subjects (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487678 TI - Partial correction of impaired creatinine kinase activity in diabetic rat heart by physical training. PMID- 8487679 TI - Hypertension in pregnancy. PMID- 8487680 TI - Randomised controlled trials: the challenge of Archie Cochrane. PMID- 8487681 TI - The changing face of clinical trials in Australia. PMID- 8487682 TI - Triplets and quadruplets born in Victoria between 1982 and 1990. The impact of IVF and GIFT on rising birthrates. AB - OBJECTIVES: To examine the perinatal characteristics of all higher order multiple births (133 sets of triplets and six sets of quadruplets) in the State of Victoria between 1982 and 1990. To compare the rising higher order multiple birth rates in Victoria with those in the other States of Australia, and to assess the impact of in-vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) on these rising birth rates. DESIGN: Retrospective review of all higher order multiple births registered in Victoria and other States of Australia between 1982 and 1990, and in particular those resulting from IVF and GIFT. DATA SOURCES: Victorian Perinatal Data Collection Unit, Australian Bureau of Statistics, National Perinatal Statistics Unit, data from Victorian IVF and GIFT units. MAIN OUTCOME MEASURES: Higher order multiple birth rates and perinatal mortality rates. RESULTS: The higher order multiple birth rates in Victoria rose from 3.5 per 10,000 in 1982 to 10.9 per 10,000 in 1990. The average perinatal mortality rates for the Victorian triplets and quadruplets born during this period were 10.8% and 25.0%, respectively. The rates of caesarean section were 70% and 83%; the proportions of deliveries in level III hospitals, 75% and 100%; and the mean maternal lengths of stay in hospital, 32 and 57 days, respectively. Endotracheal intubation was performed at birth in 18.5% of all infants. The proportions of triplet and quadruplet pregnancies in Victoria owing to IVF and GIFT rose during this period, reaching a peak of 42% in 1990. In the other States, the birth rates for higher order multiples increased at 1.8 times the rate observed for Victoria, with IVF and GIFT contributing to an estimated 43% of these conceptions between 1985 and 1989. CONCLUSION: Restrictions on the numbers of embryos/oocytes transferred during IVF and GIFT should reduce the frequency of higher order multiple births. PMID- 8487683 TI - Birthweight-specific trends in perinatal mortality by hospital category in South Australia, 1985-1990. AB - OBJECTIVE: To investigate differences by birthweight in risk of perinatal death between level 3 hospitals (which provide care for high risk pregnancies and neonatal intensive care) and other hospitals in South Australia, using perinatal data for the 1985-1990 period. DESIGN: Analysis of birthweight-specific trends in risk of perinatal death by hospital category for singleton births, adjusting for risk factors. SUBJECTS: 114 725 singleton births of at least 400 g birthweight (or at least 20 weeks' gestation) born in hospitals in the 1985-1990 period and notified to the perinatal data collection. MAIN OUTCOME MEASURE: The relative odds of a perinatal death, as opposed to a live birth which survived the neonatal period. RESULTS: Births at level 3 hospitals had a higher crude risk of perinatal death than those at other hospitals, but this was due to the higher frequency of low birthweights at level 3 hospitals. For birthweights under 2000 g, and especially for the very low birth-weights, there was a higher risk at non-level-3 than level 3 hospitals. There was also the unexpected finding that births at level 3 hospitals in the 2500-2999 g range had a comparatively high risk of perinatal death. There was little difference in risk for births of higher birthweight. CONCLUSIONS: The greatly reduced risk of perinatal death in level 3 hospitals for babies with birthweights under 2000 g seems likely to be due to the specialist services in these hospitals. Further investigation is required to determine why babies in the 2500-2999 g range of birthweights had a comparatively high risk of perinatal death at these hospitals. This appears to be due, at least in part, to an excess contribution of deaths from congenital abnormalities. Also, it seems that the higher prevalence of complications in pregnancy in level 3 hospitals, and the transfers for induction of labour after intrauterine fetal death, would have made a contribution. These same factors may also have affected the risk in level 3 hospitals for higher birthweight births. PMID- 8487684 TI - Role of percutaneous cervical cordotomy for pain of malignant origin. AB - OBJECTIVE: To discuss the place of, and indications for, percutaneous cervical cordotomy in the relief of cancer pain and to report a series of patients on whom the operation was performed at the Royal Brisbane Hospital. SETTING AND PATIENTS: Two hundred and seventy-three patients underwent percutaneous cervical cordotomy of approximately 4000 cancer patients referred to the Pain Clinic, Royal Brisbane Hospital, a tertiary referral centre, in the years 1979 to 1991. Both public and private patients were included. All received the same level of clinical care from the authors, all operations being performed by the first author. The major indication for the procedure was unilateral cancer pain below the head and neck, but other factors influencing the decision for operation were respiratory function, age, general condition and expectation of life. MAJOR OUTCOME MEASURES: Effectiveness of pain relief, first-week mortality, quality of life. RESULTS: Satisfactory pain relief was achieved in 89% of patients. First-week mortality was 3.3%. Long-term survivors (eight and five years) have remained free of their original pain. Particular emphasis is placed on the successful pain relief in 114 patients suffering from primary lung cancer, including mesothelioma. Side effects and complications have been few. CONCLUSION: Unilateral percutaneous cervical cordotomy is a valuable method of treatment of cancer pain in selected patients. The procedure has a special place in the treatment of the large group of patients suffering pain associated with primary lung cancer including mesothelioma. We support the view of overseas workers that percutaneous cervical cordotomy is the only effective method of achieving stable pain control in these patients, many of whom are referred late. PMID- 8487685 TI - Bacteraemia and fungaemia in an Australian general hospital--associations and outcomes. AB - OBJECTIVE: To obtain a comprehensive overview of bacteraemia and fungaemia in a general hospital and thus to determine the incidence, primary sites of sepsis, organisms involved and associated mortality. DESIGN: A prospective laboratory and clinical evaluation of all episodes where microorganisms were cultured from blood over one year. SETTING: The two major hospitals in the Australian Capital Territory which have both community and referral functions. These hospitals provide obstetric and paediatric services along with adult medicine and surgery. PATIENTS: All those who acquired bacteraemia in hospital or presented with a blood-stream infection documented by a positive blood culture. RESULTS: During 1990, 474 clinical episodes of bacteraemia or fungaemia were detected in 446 patients. Significant isolates were identified in 317 of these episodes. The incidence of significant sepsis was 8.1 episodes per 1000 admissions. The most common organisms isolated were Staphylococcus aureus (75 episodes) and Escherichia coli (70 episodes). One hundred and twenty-eight episodes were hospital acquired. Intravenous catheters were the primary sites of sepsis in 68 episodes. Fifty patients died. Higher mortality rates were associated with patients over 60 years of age, respiratory tract sepsis, endocarditis and the presence of an underlying malignancy. CONCLUSION: Bacteraemia and fungaemia are common problems. Nosocomial bacteraemia accounted for 40% of episodes. Half of these nosocomial infections were iatrogenic. Many of the episodes of intravenous catheter sepsis were potentially preventable. Ongoing programs of surveillance of bacteraemia, with the evaluation of primary site, associated features and mortality, are essential to monitor the dimensions of this problem and aid in implementing effective preventive strategies. PMID- 8487686 TI - ACE-inhibitors, calcium antagonists and low systemic vascular resistance following cardiopulmonary bypass. A case-control study. AB - OBJECTIVE: To investigate whether the syndrome of low systemic vascular resistance (SVR) following cardiac surgery and cardiopulmonary bypass (CPB) is more common in patients taking angiotensin-converting enzyme inhibitors (ACE inhibitors) or calcium antagonists. DESIGN: A case-control study, with cases ("low SVR syndrome") identified from intensive care unit observation charts. These cases were each matched to two controls identified from the same group of charts during the same time period. Exposure (ACE-inhibitors or calcium antagonists) was determined in a blinded fashion from the patient's medical record. SETTING: Cardiothoracic surgical unit in a teaching hospital. PARTICIPANTS: We identified 42 cases of low SVR syndrome; these were matched to 84 controls. RESULTS: There was no association between therapy with ACE inhibitors and the low SVR syndrome following CPB (odds ratio [OR], 1.33; 95% confidence interval [CI], 0.53-3.34), nor with calcium antagonists (OR, 0.49; 95% CI, 0.21-1.13). The incidence of the low SVR syndrome was 7.4%. Patients who develop the low SVR syndrome are more likely to be treated with noradrenaline, adrenaline and dopamine, and spend more time in the cardiothoracic intensive care unit. CONCLUSION: The "low SVR syndrome" following CPB is not associated with preoperative therapy with ACE-inhibitors or calcium antagonists. PMID- 8487687 TI - Genetics of connective tissue disease. PMID- 8487688 TI - Vector-borne diseases and their control. AB - Control of the vector is usually a crucial factor in control programs for tropical diseases spread by insect vectors. Successful control programs aim at vulnerable points in the interactions between the vector, the reservoir host, the pathogen, the human host, and the environment. The objective is to prevent potential transmission, or interrupt actual transmission, by reducing the abundance, longevity, or host contact of the vector--whichever is most appropriate to the particular pathogen or disease and the local situation. The importance of individual assessment in the light of local conditions and a knowledge of the biology of the local vector is stressed. The vector-borne diseases discussed here are malaria, filariasis, arbovirus diseases, trypanosomiasis, leishmaniasis, plague and rickettsiosis. PMID- 8487689 TI - Antibiotics in acute respiratory infections. AB - In the absence of clear research-based guidelines, this paper gives practical empirical directions for deciding when to prescribe antibiotics in acute respiratory infections, and how not to prescribe them when their use is inappropriate. Antibiotics probably have no effect on the outcome of most respiratory infections, viral or bacterial. When even the small chance of benefit seems to outweigh the risks and disadvantages, penicillin remains the best first line agent for most respiratory infections, owing to the range of pathogenic bacteria likely to be encountered and its low side effect profile. Convincing some patients that antibiotics are not necessary is a sometimes difficult, but worthwhile task. PMID- 8487690 TI - Management of hypertension in pregnancy: executive summary. Australasian Society for the Study of Hypertension in Pregnancy. PMID- 8487691 TI - Effect of ambient temperature on SIDS rate. AB - OBJECTIVE: To examine the relationship between ambient temperature and rate of sudden infant death syndrome (SIDS). SUBJECTS AND SETTING: All infants with SIDS occurring during 1980-1989 in the Sydney metropolitan area. RESULTS: The SIDS rate varied more than threefold over the months of the year and peaked at the minimum daily temperature in July. The rate was negatively linearly related to both the monthly mean minimum and maximum daily temperatures. Both relationships were highly significant (P < 0.001). CONCLUSION: The significant relationship between daily temperature and SIDS rate means either that daily temperature is an excellent indicator of the cold weather conditions that have a profound effect on the rate of SIDS or that temperature itself plays a direct role in the cause of SIDS. PMID- 8487693 TI - Fatal brown snake (Pseudonaja textilis) envenomation despite the use of antivenom. AB - OBJECTIVE: To report two cases of fatal brown snake envenomation in adults despite the use of appropriate antivenom. CLINICAL FEATURES: Two men, aged 42 and 39, one with a history of hypertension, suffered fatal brown snake envenomation in Queensland. One believed he had been stung by a wasp. Both developed cardiorespiratory failure within one hour of the bite, followed by coagulopathy and pulmonary oedema. One patient developed fulminant multiorgan failure. INTERVENTION: Both patients died despite the administration of large doses of appropriate antivenom and full supportive care. CONCLUSION: Brown snake bites remain extremely dangerous despite the availability of specific antivenom. In severe cases associated with myocardial depression and gross coagulopathy, death may occur rapidly despite the use of conventional doses of antivenom. In such patients the antivenom requirement may be much greater than is currently recommended. PMID- 8487692 TI - D-dimer in the early diagnosis of thromboembolic disease in acute spinal injuries. AB - The role of monitoring plasma levels of D-dimer (XDP) as a diagnostic aid for thromboembolic disease was investigated in 267 patients admitted for acute care to the Prince Henry Hospital Spinal Unit. Elevated plasma XDP levels were found in 103 patients (39%) and a diagnosis of thromboembolic disease was made in 33. Thromboembolic disease was not found in patients whose XDP levels remained normal. PMID- 8487694 TI - Henri Parinaud and his syndrome. PMID- 8487695 TI - New horizons in the treatment of multiple sclerosis. AB - OBJECTIVE: To review and discuss novel therapeutic approaches to multiple sclerosis (MS), particularly strategies designed to modulate immunopathogenetic mechanisms. DATA SOURCES: Recent medical and scientific publications and the proceedings of recent conferences in Australia and the United States. CONCLUSIONS: Clearer understanding of the pathogenetic mechanisms leading to inflammation and demyelination in MS is suggesting new strategies for intervention. Both antigen-specific and non-antigen-specific immunomodulation can be achieved in animal models, and human clinical trials of several new agents can be expected shortly. PMID- 8487696 TI - Knowledge of Hib disease and vaccine in long day care centres. PMID- 8487697 TI - Massive disc sequestration after spinal manipulation. PMID- 8487698 TI - Ipratropium bromide nasal spray. PMID- 8487699 TI - Protocols for vegetative patients. PMID- 8487700 TI - Oliguria and haemorrhage after intramuscular injection of ketorolac trometamol. PMID- 8487701 TI - Ketorolac. PMID- 8487702 TI - Munchausen syndrome by proxy. PMID- 8487703 TI - Treatment of psoriasis with topical auranofin. PMID- 8487704 TI - Reduction in cervical "whiplash" after new motor vehicle accident legislation in Victoria. PMID- 8487705 TI - The hand diagram. PMID- 8487706 TI - Obesity--a major health problem. PMID- 8487707 TI - Geriatric medicine--spanning the generations. PMID- 8487708 TI - Importance of resistant Klebsiella spp. in Victoria. PMID- 8487709 TI - Fluoxetine--delayed half-life and an adverse event. PMID- 8487710 TI - Sudden infant death syndrome (SIDS) in South Australia related to sleeping conditions. PMID- 8487711 TI - Evaluation of a hospital-based education program for aboriginal people with diabetes. PMID- 8487712 TI - Drug utilisation. PMID- 8487713 TI - Traveller's diarrhoea associated with a cyanobacterium-like body. PMID- 8487714 TI - Sports medicine in Australia. PMID- 8487715 TI - Lipoprotein(a): important risk factor or passing fashion? PMID- 8487716 TI - Diabetes and impaired glucose tolerance: using the new criteria. PMID- 8487717 TI - Planned sexual behaviour of young Australian visitors to Thailand. AB - OBJECTIVE: To research the knowledge of AIDS and other sexually transmitted diseases among young Australian tourists to Thailand, and their intended sexual behaviour. DESIGN AND SETTING: A cross-sectional survey by anonymous, self administered questionnaire, of persons seeking pre-travel medical advice in private clinics in five Australian cities. PARTICIPANTS: 213 consecutive patients travelling to Thailand without a spouse or partner. RESULTS: Only 34% of the sample reported a definite intention not to have sex in Thailand. Regarding choice of potential partners: 24.5% more men than women said they would have sex with a Thai national; 13.7% of men said they would have sex with a "bar girl"; and 21.7% more women than men said they would choose a fellow Australian traveller. Eighty-two per cent of the sample reported that they would use condoms 100% of the time, and there was no significant difference between the number of men and women who expressed this intention. CONCLUSIONS: Although not obviously "sex tourists", many young Australian travellers are likely to have sex while visiting Thailand. These data have important implications for education and prevention programs to control the spread of human immunodeficiency virus (HIV) and other sexually transmitted diseases. PMID- 8487718 TI - Diabetes mellitus. AB - Elderly diabetic patients require education in dietary therapy, physical activity, and self-monitoring of glycaemic control. However, rather than tight control, treatment should aim for a simple regimen which will relieve symptoms without introducing complications of its own. It is important to be aware of possible interactions between hypoglycaemic agents and drugs given for other diseases. PMID- 8487719 TI - Otitis media in general practice. PMID- 8487720 TI - FISH and the technicolour revolution. Molecular cytogenetics and its application in chromosome analysis today. PMID- 8487721 TI - Australia's contribution to tropical health: past and present. AB - Australian research workers have made important contributions to tropical medicine and tropical public health. Recognised high points of international significance (for example, Joseph Bancroft and filariasis, 1876; Thomas Bancroft and dengue fever, 1906; Burnet and Australian X disease, 1934; Derrick and Q fever, 1937; and Fairley and malaria, 1947) must be seen in the context of much detailed work of national relevance by institutions and individuals. The directions of Australian research can be related to several major themes: the large extent of Australia that is tropical or subtropical; interactions with neighbouring countries, especially Papua New Guinea; and concern for the health of Australian Aborigines. PMID- 8487722 TI - The natural history of aortic dilatation in Marfan syndrome. AB - OBJECTIVES: To determine the relationship between age and aortic dilatation in patients with Marfan syndrome and to define the rate of progression of aortic dilatation in these patients. DESIGN: All patients were evaluated in a multidisciplinary clinic to establish a firm diagnosis of Marfan syndrome. Aortic dimensions were measured by echocardiography and patients with Marfan syndrome were followed up with annual physical and echocardiographic examinations to detect any change in aortic diameter over the subsequent four years. PATIENTS: One hundred and fifty-seven patients were referred to the clinic for assessment, of whom 40 exhibited diagnostic features of Marfan syndrome. Only 24 of these patients had previously been diagnosed with Marfan syndrome, while 17 other patients, previously diagnosed with Marfan syndrome, had insufficient clinical features to justify the diagnosis. RESULTS: Among the 40 patients (19 male, 21 female) with Marfan syndrome (mean age, 28 +/- 15 years), the prevalence of cardiovascular abnormalities was 90%. Aortic root dilatation was present in 78% of patients, aortic regurgitation in 28%, mitral valve prolapse in 65% and mitral regurgitation in 35%. Mean aortic root diameter in the Marfan patients (21.4 +/- 4.0 mm/m2 body surface area) markedly exceeded that of age and sex matched controls without Marfan syndrome (14.9 +/- 2.2 mm/m2) and that of first-degree relatives without Marfan syndrome (15.3 +/- 2.9 mm/m2). The occurrence of aortic dilatation in Marfan syndrome was variable, with patients as young as 20 years exhibiting severe dilatation. All patients with Marfan syndrome exhibiting aortic dilatation were advised to take beta-adrenergic blocking drugs, unless contraindicated, in an effort to retard the rate of aortic dilatation. Among 33 patients followed up for at least one year, 14 (42%) exhibited an increase in aortic diameter of at least 2 mm, while 16 of 23 patients (70%) followed up for at least three years exhibited similar progression of aortic dilatation. The overall mean rate of dilatation in the Marfan patients was 1.9 mm per year. Nine patients developed aortic dilatation of more than 50 mm diameter during four years' follow-up and required surgical repair of the aorta. Each of these patients is well at between three months' and four years' follow-up. CONCLUSIONS: Aneurysmal dilatation of the aorta is a common complication of Marfan syndrome and may become manifest at an early age. Furthermore, aortic dilatation can progress rapidly, even in the absence of symptoms. Individuals with Marfan syndrome should have annual echocardiographic examinations to monitor aortic root dimensions, and those exhibiting rapid progression of aortic dilatation or an aortic root diameter in excess of 50 mm, should be considered for elective composite graft repair of the aorta. PMID- 8487723 TI - Revised criteria for diagnosis of diabetes. Working Party of the Australian Diabetes Society, Australian Association of Clinical Biochemists and the Royal College of Pathologists of Australasia. PMID- 8487724 TI - The 18 to 20 week obstetrical scan. A joint statement from the Australasian Society for Ultrasound in Medicine, the Royal Australian College of Obstetricians and Gynaecologists and the Royal Australasian College of Radiologists. AB - The Australasian Society for Ultrasound in Medicine, The Royal Australian College of Obstetricians and Gynaecologists and the Royal Australasian College of Radiologists have produced jointly the accompanying document on the 18-20 week obstetrical scan. It is an important document not only for the sonologists and sonographers but also for clinicians who request ultrasound examinations for pregnant women, so that they may have a better idea of what the examination should cover and its limitations. PMID- 8487725 TI - Planning bedside teaching--5. Debriefing after clinical interaction. PMID- 8487726 TI - The poisoned tap. PMID- 8487727 TI - HIV in the suburbs. PMID- 8487728 TI - HIV infection in drug and alcohol practice. PMID- 8487729 TI - The effects of danazol on vocal parameters--is an objective prospective study needed? PMID- 8487730 TI - Condoms and HIV. PMID- 8487731 TI - Sexually active or sexually mobile. PMID- 8487732 TI - The National Heart Foundation of Australia Pick the Tick program. PMID- 8487733 TI - An aid to laparoscopic hernioplasty--balloon dissection. PMID- 8487734 TI - Carcinoma of the breast. PMID- 8487735 TI - Laparoscopic cholecystectomy. PMID- 8487736 TI - Re-entry syndrome. PMID- 8487737 TI - Carpet cleaning. PMID- 8487738 TI - Medicolegal assessment. PMID- 8487739 TI - "Confidence buster". PMID- 8487740 TI - Lowering cholesterol. PMID- 8487741 TI - The potential for teratogenicity of vitamin A and its congeners. PMID- 8487742 TI - The potential organ donor. PMID- 8487743 TI - Drugs of choice for cancer chemotherapy. PMID- 8487744 TI - Smoking control among health-care workers--World No-Tobacco Day, 1993. PMID- 8487745 TI - Influence of religious leaders on smoking cessation in a rural population- Thailand, 1991. AB - Despite substantial increases in smoking and intensified marketing of tobacco products in developing countries (1), efforts to prevent tobacco use through community-based approaches have been limited (2,3). In Thailand, an estimated 9 million children will become smokers, and more than 2 million will die prematurely as adults from smoking-related illnesses (1,4). Because of these risks, the Department of Community and Social Medicine, Mae Sot General Hospital (MSGH), and the Field Epidemiology Training Program (FETP) of the Thai Ministry of Public Health recently assessed the impact of community-based smoking prevention efforts initiated by religious leaders. This report describes this program and summarizes the assessment. PMID- 8487746 TI - School-based tobacco-use prevention--People's Republic of China, May 1989-January 1990. AB - Tobacco consumption has increased markedly in the People's Republic of China (PRC) since the 1960s (1,2). In 1984, when the prevalence of cigarette smoking was 61% among men and 7% among women, approximately 250 million persons in PRC smoked tobacco products (1). In 1988, among junior high school students in PRC, 34% of boys and 4% of girls reported smoking at least occasionally (3). To increase public knowledge of the health consequences of cigarette smoking, promote healthier attitudes among elementary school students, and motivate fathers who smoke to quit, the Zhejiang Center for Health Education developed and implemented a school-based smoking-intervention program in the Jiangan district of Hangzhou from May 1989 through January 1990. This report summarizes an assessment of this program. PMID- 8487747 TI - Measles--United States, 1992. AB - As of January 2, 1993 (week 53), local and state health departments reported a provisional total of 2200 measles cases for 1992 (1)--a 77% decrease from the 9643 cases reported for 1991 (2), and a 92% decrease from the 27,786 cases reported for 1990 (3). Cases were reported from 36 states and the District of Columbia. This provisional total is one of the lowest annual totals reported in the United States; fewer cases were reported only in 1982 (1714 cases) and 1983 (1497 cases) (4). This report summarizes epidemiologic characteristics of measles cases reported for 1992 and compares them with cases reported during 1989-1991. PMID- 8487748 TI - NIOSH alert: request for assistance in preventing falls and electrocutions during tree trimming. PMID- 8487749 TI - NIOSH alert: request for assistance in preventing worker injuries and deaths caused by falls from suspension scaffolds. PMID- 8487750 TI - Identification of an autoinhibitory domain in the insulin receptor tyrosine kinase. AB - We have tested the hypothesis that activation of the insulin receptor tyrosine kinase is due to autophosphorylation of tyrosines 1146, 1150 and 1151 within a putative autoinhibitory domain. A synthetic peptide corresponding to residues 1134-1162, with tyrosines substituted by alanine or phenylalanine, of the insulin receptor beta subunit was tested for its inhibitory potency and specificity towards the tyrosine kinase activity. This synthetic peptide gave inhibition of the insulin receptor tyrosine kinase autophosphorylation and phosphorylation of the exogenous substrate poly(Glu, Tyr) with an approximate IC50 of 100 microM. Inhibition appeared to be independent of the concentrations of insulin or the substrate poly(Glu, Tyr) but was decreased by increasing concentrations of ATP. This same peptide also inhibited the EGF receptor tyrosine kinase but not a serine/threonine protein kinase. These results are consistent with the hypothesis that this autophosphorylation domain contains an autoinhibitory sequence. PMID- 8487751 TI - A novel plant membrane proteoglycan which causes anorexia in animals. AB - Hunger and satiety are complex interplay of several factors in human and animal species. Reduced food intake has also been observed under various pathological conditions. Earlier, we have been able to isolate an endogenous glycoprotein from erythrocyte membranes, which causes anorexia in rats. In the present study, a similar anorexigenic proteoglycan from Mung bean sprout membranes has been isolated and purified. The proteoglycan (50 kDa) consisted of 70-85% carbohydrate with galactose, glucose galactosamine and mannose as the main sugars. Protein part on analysis showed higher glutamic acid and serine content. This proteoglycan reduces food intake when injected in rats deprived of food for 96 hr as well as normally fed rats, mice and rabbits without any rebound. The TCA soluble proteoglycan from different plant sources have also been compared for their anorexigenic activity. The similarities observed among plant and animal cell membrane proteoglycans with satietins isolated from human blood plasma could be due to membrane origin of satietins. PMID- 8487752 TI - Influence of liposome charge and composition on their interaction with human blood serum proteins. AB - Lipid composition and specially their electrostatic properties, were found to greatly influence the stability of liposomes in human blood serum. The amount and type of serum proteins bound to the liposomes were also clearly influenced by lipid composition and charge of liposomes. A good correlation was found between the amount of serum proteins adsorbed to a given type of liposome and its instability as measured by the release of an encapsulated fluorescent probe. Liposomes that bind the highest amount of protein were the least stable, except for the case of liposomes containing gangliosides, which were fairly stable even at a high amount of bound protein. Liposomes with neutral charge containing phosphatidylcholine were the most stable and bound the lowest amount of protein. Liposomes with positive charge behaved similarly to those with neutral charge. However, the stability of negatively charged liposomes was very dependent on their composition. Those liposomes containing only one class of negatively charged phospholipids bound a great amount of protein and were very unstable. However, those liposomes containing also phosphatidylcholine bound less protein and were more stable. The examination of the electrophoresis patterns of serum proteins bound to the different types of liposomes indicated the presence of specific proteins which correlated with liposome instability. PMID- 8487753 TI - Effect of streptozotocin and nicotinamide upon FAD-glycerophosphate dehydrogenase activity and insulin release in purified pancreatic B-cells. AB - Purified rat pancreatic insulin-producing B-cells, which display a 12-fold higher activity of FAD-linked glycerophosphate dehydrogenase than other islet endocrine cells, were exposed for 30 min to 2 mM streptozotocin and subsequently cultured for 2 days in the absence or presence of 2 mM nicotinamide. Streptozotocin decreased by 54% the number of B-cells and, in surviving cells, lowered by 75% the activity of FAD-linked glycerophosphate dehydrogenase, whilst failing to affect that of glutamate dehydrogenase. This coincided with a 42-51% reduction of insulin secretion, when expressed relative to either the DNA or hormonal content of surviving cells. After exposure to streptozotocin, the presence of nicotinamide in the culture medium reduced cell death by 44% and also reduced the deleterious effects of streptozotocin upon both the enzymic and secretory activities of surviving cells. These findings indicate that the decreased activity of FAD-linked glycerophosphate dehydrogenase previously documented in pancreatic islets from streptozotocin-injected rats, as well as the protective effect of nicotinamide thereupon, are not attributable solely to changes in the number of B-cells but also to an altered enzymic activity in surviving B-cells. The latter anomaly may account, in part at least, for an impaired B-cell secretory response to D-glucose. PMID- 8487754 TI - Ferrous-iron induces lipid peroxidation with little damage to energy transduction in mitochondria. AB - Addition of ferrous sulfate, but not ferric chloride, in micromolar concentrations to rat liver mitochondria induced high rates of consumption of oxygen. The oxygen consumed was several times in excess of the reducing capacity of ferrous-iron (O:Fe ratios 5-8). This occurred in the absence of NADPH or any exogenous oxidizable substrate. The reaction terminated on oxidation of ferrous ions. Malondialdehyde (MDA), measured as thiobarbituric acid-reacting material, was produced indicating peroxidation of lipids. The ratio of O2:MDA was about 4:1. Pretreatment of mitochondria with ferrous sulfate decreased the rate of oxidation (state 3) with glutamate (+ malate) as the substrate by about 40% but caused little damage to energy transduction process as represented by ratios of ADP:O and respiratory control, as well as calcium-stimulated oxygen uptake and energy-dependent uptake of [45Ca]-calcium. Addition of succinate or ubiquinone decreased ferrous iron-induced lipid peroxidation in intact mitochondria. In frozen-thawed mitochondria, addition of succinate enhanced lipid peroxidation whereas ubiquinone had little effect. These results suggest that ferrous-iron can cause peroxidation of mitochondrial lipids without affecting the energy transduction systems, and that succinate and ubiquinone can offer protection from damage due to such ferrous-iron released from the stores within the cells. PMID- 8487755 TI - Triiodo-L-thyronine stimulates glycogen synthesis in rat hepatocyte cultures. AB - The hyperthyroid state is associated with low hepatic glycogen levels, but paradoxically with a high activity of glycogen synthase and low activity of glycogen phosphorylase. We determined the effects of triiodo-L-thyronine (T3) on glycogen synthesis and glycogen synthase activity in rat hepatocytes in vitro. Culture of rat hepatocytes with T3 (100 nM-1 microM) for 16 h-40 h increases glycogen synthesis from glucose and gluconeogenic precursors. The stimulation of glycogen synthesis by T3 was associated with an increase in the activity of glycogen synthase and was additive with the long-term effects of insulin but not with the short-term stimulation of glycogen synthesis by insulin. Culture of hepatocytes with T3 (at concentrations up to 1 microM) did not affect the responsiveness of glycogen synthesis to short-term stimulation by insulin but culture with 10 microM-T3 decreased the responsiveness to insulin without affecting the basal rate. It is suggested that the high activity of glycogen synthase in the hyperthyroid state is due to a direct effect of T3 on the hepatocyte, but the low hepatic glycogen content is probably due to either secondary metabolite and/or endocrine changes or to impaired responsiveness to insulin. T3 may have an anabolic role in the control of hepatic glycogen storage in the euthyroid postprandial state. PMID- 8487756 TI - Pregnancy specific beta 1-glycoprotein in human intestine. AB - Pregnancy-specific beta 1-glycoprotein (PSG) transcripts have been identified in a number of placental and non-placental tissues. Using a placental PSG cDNA probe to screen a normal human intestinal cDNA library we have isolated 22 hybridizing clones. These clones could be divided into four groups. Nucleotide sequence analysis showed that one group of clones correspond to functional and another group correspond to non-functional PSG cDNAs. The other two groups are homologous to the nonspecific cross-reacting antigen (NCA) and biliary glycoprotein (BGP), both of which are members of the carcinoembryonic antigen (CEA) family. Thus, PSG, NCA and BGP are co-expressed in normal human intestine. RNA and immunoblot analysis, along with polymerase chain reaction amplification further confirm the expression of PSG in human intestinal tissue. PMID- 8487757 TI - Expression analysis of the mixed function oxidase system in rat brain by the polymerase chain reaction. AB - Metabolism of therapeutic drugs in the body by the mixed function oxidase system is an important consideration in the analysis of a drug's effectiveness. P450 dependent metabolism within the brain of a neuro-specific drug may affect the drug's course of action. To determine whether cytochrome P450 was expressed in brain, RNA was isolated from the whole brains of rats treated with a variety of known hepatic P450 inducers, including amitriptyline, imipramine, isosafrole, phenobarbital, and beta-naphthoflavone. The RNA was analyzed for the presence of P450 isozymes by the PCR technique. Differential expression of P450IA1, P450IIB1, P450IIB2, P450IID, and P450IIE1 was detected in the brain samples, depending on the treatment. Cytochrome P450 reductase expression was also detected in the brain samples, giving strong evidence that the brain contains a competent mixed function oxidase system under all conditions studied. PMID- 8487758 TI - [Mapping vaccinia virus genes]. AB - This is a critical review of the modern methods of gene mapping in the vaccinia virus genome. Experimental data are given on the localization of the vaccinia virus genes. Major attention is paid to the functions of the proteins encoded by the mapped genes. PMID- 8487759 TI - [The role of oligophosphate and nucleoside fragments upon the interaction of a nucleotide with RecA protein]. AB - Pyrophosphate and 1-pyrophospho-5-phosphoribose displace the nucleotide from the complex with RecA protein (in the absence of DNA). Adenosine, AMP, inorganic phosphate riboso-5-phosphate have no effect. Pyrophosphate causes the dissociation of RecA-ssDNA-complex in the same manner as ADP, circular hexaphosphate has no effect. In the complex with RecA protein the dissociation constant for pyrophosphate is 1.6 mM and 710 mM for adenosine. It is proposed that the oligophosphate is the main binding group in the RecA-nucleotide interaction. Two vicinal "closed" -O and one terminal "open" oxygenous =O-groups of oligophosphate take part in the binding. The nucleoside fragment alone cannot provide the firm binding of the nucleotide with the protein, but probably is responsible for the specificity of the nucleotide to protein binding. PMID- 8487760 TI - [Immunochemical analysis of Escherichia coli expression products of I3 and A2 genes of vaccinia virus strain L-IVL genome]. AB - Genes I3 and A2 of the vaccinia virus strain L-IVP DNA were cloned into bacterial expressing vectors. The monospecific antisera to the expression products of these genes in E. coli were obtained. By means of immunochemical cross-analysis two polypeptides of equal electrophoretic mobility were found in the virion preparations in the band of the major envelope protein p35. The major of them is the product of gene I3, and the minor is encoded by gene A2. PMID- 8487761 TI - [Nuclear peptides, specifically binding oligonucleotides]. AB - Interaction of alkylating derivatives of oligonucleotides with nuclear extracts from mammalian cells has been investigated. Three modified 1.5-, 3.0-, and 6.0 kDa proteins were detected in nuclear extracts from human and murine cells. The 1.5-kDa and 3.0-kDa proteins were also detected in insect, plant, yeast, and bacterial cells. The ubiquity of the proteins suggests their important role in cellular metabolism. PMID- 8487762 TI - [Quantitative determination of the accessible surface of globular proteins by tritium planigraphy]. AB - At the last time the term "accessible surface" is used for a description of protein structure. The tritium planigraphy was used for quantitative detection of the accessible surface. The experimental dependence of an interaction probability of the tritium atoms with globular proteins with calculated accessible surface areas was obtained. The method was proposed on the basis of the information about the reactivity of amino acids residues and was used for the determination of an accessible surface of parvalbumin III of pike. PMID- 8487763 TI - [Ionization energy and glycoside bond rupture energy of nucleosides, suppressing the reproduction of the human immunodeficiency virus (HIV)]. AB - By photoionization mass spectrometry the energy characteristics were investigated for a series of nucleosides whose triphosphates possess anti-HIV activity. The electron-donor ability (a value reciprocal to ionization energy) does not correlate with the biological activity of corresponding nucleotides. The energy of glycoside bond rupture depended on modification in deoxyribose. PMID- 8487764 TI - [Characteristics for determining nonpolar amino acid residues in amino acid sequences of certain globular proteins]. AB - A method of quantitative characterization of nonpolar residue distribution in amino acid sequences of globular proteins is proposed. It consists in determination of ratios of residues belonging to two selected amino acid subgroups: leucine, phenylalanine, tyrosine, tryptophan; and alanine, valine, isoleucine. It was found that the values of the proposed index of analyzed proteins are in the range 0.51-1.27, the mean value being 0.90 +/- 0.10. PMID- 8487765 TI - [In vitro suppression of translation of tick-borne encephalitis virus RNA using antisense nucleotides]. AB - Effect of antisense oligodeoxyribonucleotides on in vitro translation of RNAs corresponding to fragments of the tick-borne encephalitis virus genome has been investigated. Sequences optimal for oligonucleotide binding and translation arrest have been identified. The most efficient oligonucleotide (17-mer) at a concentration of 2.5 microM completely arrests translation of the RNA coding for the NS3 protein. PMID- 8487766 TI - [Interaction of mRNA analogs--oligoribonucleotides AUGU3, AUGU6 and (pU)6 with 80S ribosomes from human placenta in the presence of related tRNA and a protein synthesizing system]. AB - Binding of oligoribonucleotides AUGUn (n-3 and 6) and (pU) to 80S ribosomes from human placenta in the presence of cognate tRNAs and a "ribosome-free" protein synthesizing system from rabbit reticulocytes has been studied. The binding of the mRNA analogues resulted in formation of stable post-translocational complexes (which may be easily isolated by centrifugation in sucrose density gradient): 80S.AUGU3.MetPhe-tRNA(Phe); 80S.AUGU6.Met(Phe)2.tRNA(Phe); 80S.(pU)6.(Phe)2 tRNA(Phe). In these complexes the ratios of the bound ligands are close to the theoretically expected values. Comparison of the results obtained with the previously reported data on nonenzymatic binding of oligouridylates and Phe tRNA(Phe) to 80S ribosomes lead one to the conclusion that translation factors significantly stabilize the complexes of tRNA with 80S ribosomes and oligoribonucleotide templates. PMID- 8487767 TI - [Heat capacity of hydrated and dehydrated globular proteins. The denaturing increment of heat capacity]. AB - Absolute values of heat capacity for some hydrated globular proteins (11S globulin, ovalbumin, ribonuclease A, and lysozyme) have been studied by differential scanning calorimetry. It has been found that for proteins with bound water, as in the case of protein solutions, the heat capacity of denatured proteins is higher then prior to denaturation. Depending on temperature and humidity, the denatured proteins can be either in high-elastic or glass state. Specific heat capacities for these two states have the same values for all proteins and depend only on temperature with a characteristic increment of 0.55 J.g-1.K-1 at glass transition. The glass transitions were observed not only in denatured but also in native proteins. Our results indicate that the main contribution to the heat capacity increment at denaturation is connected with the thermal motion in the protein globule, which is contrast with the commonly accepted ideas. PMID- 8487768 TI - [Analysis of the spatial structure of proteins in terms of residue-residue contacts. II. Contact affinity]. AB - The possibility of detecting the mutual amino acid residue affinity when protein three-dimensional structures are described in terms of residue-residue contact matrices is discussed. The hypothesis of the lack of affinity between amino acid residues is examined; the values of the pertinent elements of the overall residue residue contact matrices prove not to be statistically different from random estimates in 91%; the chance hypothesis is rejected in 9% of cases, represented as a rule by residues with charged side groups, especially oppositely charged ones. PMID- 8487769 TI - [Gene 26 of bacteriophage T4 baseplate. II. Synthesis of a smaller peptide of gene 26 is initiated at an unusual AUU-codon]. AB - The sequence of gene 26 consisting of 624 nucleotides codes for two peptides whereby the smaller peptide (gp26*) is encoded by the 3'-end of the same open reading frame. Expression of gene 26 from plasmids, containing various fragments from the terminal part of this gene, allowed us to determine the gene 26 internal segment responsible for the initiation of gp26* synthesis. By site-directed mutagenesis the nucleotide sequence of this DNA segment has been changed, and in further expression experiments of the mutagenized gene 26 it was determined that an unusual AUU codon, triplet 114 of gene 26, is used to initiate the synthesis of the smaller peptide. Thus gene 26 encodes two peptides of M(r) 23,880 and M(r) 10,873. The regulation of the expression of gene 26 in T4-infected cells is discussed. PMID- 8487770 TI - [Analysis of reporter gene expression at different segments of the vaccinia virus genome]. AB - Two reporter genes: the firefly Photinus pyralis luciferase gene and the Escherichia coli beta-galactosidase gene were used for construction and characterization of the five unique recombinant vaccinia strain LIVP viruses expressing these genes in three nonessential regions of the virus genome. We give comparative characteristics of beta-galactosidase and luciferase activities in experiments of transient expression and expression dynamics of reporter genes by different stable recombinant viruses. Both genes are expressed with high efficiency independent on the sites of virus genome localization. It is shown that the TK-, HA- and N-regions of vaccinia virus DNA may be used for inserting foreign genes. PMID- 8487772 TI - [Three mutant forms of ribosomal protein L7/L12]. AB - Three mutant forms of the ribosomal protein L7/L12 with Ser1, Met14, and Met26 replacements with Tyr were constructed for studying the N-terminal domain of the protein. Three point mutations in the gene L7/L12 on the phage M13mp18 were generated. Recombinant plasmids containing the mutant genes were constructed on the base of expression vector pKK223-3 and plasmid pUC19. The mutant proteins were expressed in Escherichia coli cells, and methods of their purification were developed. It was found that the mutant proteins L7/L12 do not differ from the wild-type protein L7/L12 and represent a suitable object for 1H-NMR study of the L7/L12 protein. The three mutant proteins bind with the E. coli ribosome. PMID- 8487771 TI - [Comparison of the heat stability and structure close homologs--Bacillus amyloliquefaciens ribonuclease and Bacillus intermedius 7P ribonuclease]. AB - Parameters of heat denaturation and intrinsic fluorescence of barnase and its close homologue, binase, in the pH region 2-6 have been determined. Barnase heat denaturation (pH 2.8-5.5) proceeds according to the "all-or-none" principle. Barnase denaturation temperature is lower than that of binase and this difference increases from 2.5 degrees C at pH 5 to 7 degrees C at pH 3. Enthalpy values of barnase and binase denaturation coincide only at pH 4.5-5.5, but as the pH decreases the barnase denaturation enthalpy decreases significantly and in this respect it differs from binase. The fluorescence and CD techniques do not reveal any distinctions in the local environment of aromatic residues in the two proteins, and the obtained difference in the parameters of intrinsic fluorescence is due to fluorescence quenching of the barnase Trp-94 by the His-18 residue, which is absent in binase. Secondary structures of both native and denaturated proteins also do not differ. Some differences have been found in the barnase and binase electrostatic characteristics, revealed in the character of the dipole moment distribution. PMID- 8487773 TI - [Preparation of single-chained antibodies to human ferritin in Escherichia coli]. AB - We have cloned cDNA copies of the immunoglobulin heavy and light chain genes from hybridoma cells able to produce antibody against human ferritin. Variable segments of these genes were obtained using the polymerase chain reaction (PCR). The specific amplifications of ligase reaction products were carried out to combine the variable segments with DNA fragments coding for a peptide-linker and for a signal peptide of the cloned pelB gene of Erwinia carotovora. During the antiferritin single-chain antibody gene expression under the T7 RNA polymerase control in E. coli the processed molecules of recombinant proteins formed aggregates in periplasm. The reversible denaturation in the absence of reducing agents had allowed us to obtain single-chain antibodies with the original binding specificity toward human ferritin. PMID- 8487774 TI - New DNA sequences for the human complement gene C4. PMID- 8487775 TI - Mouse monoclonal anti-idiotypic antibodies to HIV p24: immunochemical properties and internal imagery. AB - Two mouse monoclonal antibodies (VIC5 and VIC6; referred to as Ab1) reacting with the p24 core antigen of HIV-1 were used to produce mouse monoclonal anti idiotypic antibodies (Ab2). Six anti-idiotypic antibodies were characterized. The five anti-idiotypic antibodies directed against VIC6 partly competed which each other and thus defined a set of overlapping idiotypes on Ab1. All 6 Ab2s inhibited the binding of the corresponding anti-p24 antibody to antigen, although four (W1, Y16, Y6, X14) were markedly more inhibitory than the remaining two (G6, Y11). All six Ab2s were antigen-inhibitable; however the interaction of G6 and Y11 with Ab1 was blocked with considerably less soluble p24 antigen than the remaining four. Correspondingly, G6 and Y11 had lower affinities for Ab1 than did W1, Y6 and X14; the affinity index of Y16 was equivalent to that of Y11. None of the Ab2s reacted with H or L chains of Ab1 after reduction on SDS-gels. Similarly, both Ab1s failed to react with the H or L chains of Ab2. These criteria appeared to define at least four of these Ab2s as internal image antibodies whose image is composed of both H and L chains. The anti-idiotypic antibodies were injected either individually or as a combined preparation of all 6 into syngeneic mice and Porton rats. Despite the presence of anti-anti idiotypic antibodies (Ab3) in these animals, when used individually no antigen specific antibodies were found. A small response to p24 antigen was induced in 3 of 6 mice using preparations containing all 6 anti-idiotypes. PMID- 8487776 TI - Induction of immune response against a short synthetic peptide antigen coupled to small neutral liposomes containing monophosphoryl lipid A. AB - We have investigated the parameters affecting the immunogenicity of a short synthetic hexapeptide associated with liposomes. The model peptide used had the sequence IRGERA which corresponds to the C-terminal hexapeptide region of histone H3. Immunogenicity was measured by the ability of anti-peptide antibodies to cross-react with the parent protein. By itself, the peptide was not able to induce significant antibody production. However, liposomes were shown to be able to render the peptide immunogenic, nevertheless a number of parameters were important: to be immunogenic the peptide had to be surface bound, rather than entrapped within the liposomes, and an adjuvant, monophosphoryl lipid A (MPLA), had to be present in the same population of liposomes. Additionally, the intensity and duration of the immune response were found to be dependent both on the charge of the liposomes; neutral liposomes yielding a longer lasting response than negatively charged liposomes, and on the immunisation schedule where a long time period between immunisation and boosting yielded a better result than a short time period. To account for these phenomena we propose a model in which surface-bound antigen targets liposomal MPLA to B lymphocytes specific for the antigen. These results demonstrate that liposomes containing the non-toxic adjuvant MPLA can act as carriers to induce a long-lasting IgG response against peptides, eliminating the need of protein carriers and conventional adjuvants. Such an approach may be useful for designing synthetic vaccines. PMID- 8487777 TI - Recombinant Fel d.I: Expression, purification, IgE binding and reaction with cat allergic human T cells. AB - This study describes the properties of the two recombinantly expressed polypeptide chains of Fel d I, the major allergen produced by the domestic cat (Felis domesticus). An inframe linker encoding polyhistidine has been added to the 5' ends of the Fel d I chains 1 and 2 cDNAs to facilitate purification using Ni2+ ion affinity chromatography. This method provides high yields in a single step of rchain 1 and rchain 2 of Fel d I with a > 90% level of purity. Polymerase chain reaction (PCR) methods were used to introduce a thrombin cleavage site (LVPR decreases GS) at the N-terminus of both chains. Thrombin cleavage of rchain 1 and rchain 2 followed by HPLC purification of the cleavage products allowed the isolation of each recombinant chain with only two additional residuals (GS) at the N-terminus of the native sequence. Amino acid sequencing analysis of the N terminus and mass spectrometry of these polypeptides demonstrated that they are highly pure and full-length. Direct ELISA assays showed that IgE from cat allergic patients binds to both rchain 1 and rchain 2 of Fel d I, demonstrating that both these chains contribute to the allergenicity of this heterodimeric protein. An examination of the reactivity of T cells derived from cat-allergic patients revealed that both polypeptide chains contribute to the T cell response to this allergen. Consequently, it is concluded that the immunological response to Fel d I is composed of a reaction at both the B and T cell level to each of the two chains that constitute the native allergen. PMID- 8487778 TI - Extensive somatic mutation in the Ig heavy chain V genes in a late primary anti hapten immune response. AB - Somatic mutations and cell lineage relationships were examined in a large panel of hybridomas derived from a single mouse 21 days after a primary immunization with NP-CGG. Among 21 lambda-bearing anti-NP hybridomas 18 distinct cell lineages were observed. Ten of the hybridomas used the V186-2 gene which is the most frequently utilized VH gene in the anti-NP response. Analysis of DNA sequence of the entire VH region of these antibodies revealed extensive somatic mutations. The selection for certain codon changes and the level of mutation observed is comparable to that observed in an early secondary anti-NP response. An unexpected observation was that one-third of the hybridomas produced IgM antibodies. Two IgM antibodies expressing the V186-2 gene contained extensive mutations in the VH region. These results indicate that once the somatic mutation process is initiated, it progresses rapidly and continues for at least two weeks during the development of the response. A highly mutated repertoire of memory B cells is formed by three weeks post-immunization that can be rapidly utilized to generate the secondary immune response. PMID- 8487779 TI - A genetically engineered human IgG with limited flexibility fully initiates cytolysis via complement. AB - A causal link between antigen induced conformational change and functional activity has been previously suggested for the triggering of immunoglobulin effector functions. To test this hypothesis an immunoglobulin with greatly restricted Fab flexibility has been created by site-directed mutagenesis. Serine119, a residue at the elbow in the first heavy chain constant domain of a mouse-human chimeric immunoglobulin, was replaced by cysteine119. The resulting mutant immunoglobulin had an additional intramolecular disulfide bond connecting the two heavy chains. This newly introduced covalent bond between antigen binding arms gave rise to a compact 'tethered' conformation which displayed lowered segmental flexibility as determined by nanosecond fluorescence depolarization anisotropy. However, the ability of this tethered immunoglobulin to initiate lysis of target cells via the complement cascade was unimpaired. Therefore, it is likely that allosteric or distortive mechanisms of conformational change induced complement activation which require unhindered 'twist' and/or 'waggle' motions of Fab are untenable. PMID- 8487780 TI - A light-scattering method for measuring the sizes of insoluble immune complexes. AB - A turbidimetric method for measuring the diameters of insoluble immune complexes, based on the wavelength dependence of their ability to scatter light, was developed. The method was validated by demonstrating that it gave experimental values for the diameters of polystyrene microspheres which were in good agreement with independently known values of these. The method was used to measure the diameters of ovalbumin:anti-ovalbumin IgG immune complexes, giving values consistent with literature measurements of the sizes of other IgG-containing immune complexes. PMID- 8487781 TI - Characterisation of rainbow trout cDNAs encoding a secreted and membrane-bound Ig heavy chain and the genomic intron upstream of the first constant exon. AB - Two different rainbow trout cDNA sequences encoding a heavy chain secreted Ig (Hs) and a part of a membrane-bound heavy chain Ig (Hm) are reported. The sequences were most similar to those encoding the Ig heavy chains (IgH) of other teleost fish. As in the Hm of the other teleost fish the rainbow trout Hm results from the splicing of the 3' end of the third constant exon (CH3) to the sequence encoding the membrane-bound domain. Analysis of a rainbow trout IgH genomic clone revealed that a joining heavy chain (JH) segment, different to the one observed in the cDNA, is located 825 bp 5' of the CH1 exon. The sequence also contains possible enhancer-like and octamer-like motifs. PMID- 8487782 TI - Cytokine gene expression in mice undergoing chronic graft-versus-host disease. AB - Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL 2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells. PMID- 8487783 TI - Identification of multiple sites of interaction between heparin and the complement system. AB - Many diverse effects of heparin on the complement system have been reported. In only a few cases have the sites or the mechanisms of these effects been identified. In order to understand these results we sought to comprehensively analyze which complement proteins interact with heparin and which do not. Purified components of the classical, alternative and terminal pathways of complement were radiolabeled and their affinity for heparin determined. Affinity chromatography of normal human serum on heparin-agarose allowed a complete analysis of complement proteins and confirmed the results obtained with radiolabeled purified components. Of the 22 complement proteins examined, 13 bound heparin (C1q, C2, C4, C4bp, C1INH, B, D, H, P, C6, C8, C9, and vitronectin) while 9 did not bind heparin (C1r, C1s, C3, Factor I, C5, C7, C3b, Ba and Bb). These observations help explain the many effects heparin has on the complement system and they identify the proteins which need to be examined in order to explain these effects. PMID- 8487784 TI - Regeneration of antidigoxin binding activity in an antibody by changes surrounding the original binding defect. AB - A panel of antibodies which differ in their L chain structures and which bind to structurally defined haptens, would be useful in investigating L chain structure and function. In a previous study, chain recombinant antibody CR24 (26-10 H, 45 20 lambda) was produced by hybridoma-hybridoma fusion. Although both parental antibodies bound digoxin with high affinity, CR24 lacked detectable digoxin binding activity. Hybridoma CR24 was subsequently fused with H chain-loss hybridomas in order to produce a panel of antibodies composed of 26-10 H chains and 26-10 "like" L chains. Two antibodies produced were CR260 which demonstrated digoxin-binding activity and CR256 which did not. CR260 and CR256 expressed only one amino acid difference (Pro to Leu at L-96). This difference resulted in the CR256 binding defect. In this report, two new antidigoxin antibodies are described. One, SR2E7, contained the Pro to Leu (L-96) defect, but still bound digoxin. Binding affinities and binding specificity patterns, as well as complete VL DNA sequence and corresponding protein sequence of the new digoxin binding antibody L chains (SR2E7 and SR1C7) are presented. Both kappa L chains are highly homologous to the 26-10 kappa L chain as well as the BALB/c germline gene K5.1. These results suggest that antibodies which are initially defective in binding activity can be cured by changing specific amino acids involved in determining the binding-site structure. Molecular modelling studies of the binding-site region were completed to address L chain structural changes induced by specific amino acid substitutions. PMID- 8487785 TI - Analysis of oligosaccharides involved in the asymmetrical glycosylation of IgG monoclonal antibodies. AB - The aim of this study is to identify the oligosaccharide residues involved in the asymmetric glycosylation of immunoglobulins. We have studied two anti-DNP monoclonal antibodies of the IgG1 isotype. Results show both qualitative and quantitative differences in the carbohydrates of both monoclonal antibodies and their fragments F(ab')2, Fab' and Fd. One of the antibodies -112D5-, which appears to be homogeneous in the Scatchard plot, has oligosaccharide residues in the L chain and in the Fd of one of the Fab'. On the other hand, 112B2 mAb, which also appears to be asymmetrically glycosylated, shows the bimodal curve characteristic of antibodies with different combining site affinities. PMID- 8487786 TI - [Comment on the contribution by H. Gotze and A. Mahdi. Fructose malabsorption and dysfunctional abdominal complaints]. PMID- 8487787 TI - [Aspects of psychosocial management of children with kidney failure and their relatives]. AB - Being confronted with chronic illness in childhood and adolescence implicates a high degree of physical and emotional burden hardly coped with without external support. For this reason psychosocial services to support children with chronic renal failure recently have been initiated at several pediatric nephrology centres during recent years. The spectrum of psychosocial burdens accompanying chronic renal failure in childhood is revealed. Tasks and interventions of psychosocial services corresponding to these burdens are described. The presented data concerning educational and vocational rehabilitation of young renal patients demonstrate the continuous need of qualified psychosocial staff, although the basic equipment of pediatric nephrology with psychosocial services has increased during the last years. In conclusion a concept of integrative patient care is illustrated by giving practical suggestions increasing the patient's compliance. PMID- 8487788 TI - [Allergy and psyche]. PMID- 8487789 TI - ["Tropical" pyomyositis in childhood]. AB - We report on a 14 year old boy, who developed bacterial pyomyositis (Staphylococcus aureus) in his left thigh. Ultrasound and magnetic resonance imaging were very helpful for the differential diagnosis and follow-up of this infection which in large skeletal muscles frequently is associated with abscess formation. Treatment consisted of antibiotics and surgical drainage. PMID- 8487790 TI - [Interaction of tolazoline and cimetidine in persistent fetal circulation of the newborn infant]. AB - A newborn was treated with tolazoline for persistent pulmonary hypertension. Oxygenation improved during continuous infusion of the drug, but gastrointestinal bleeding occurred. Therefore, cimetidine was given. After this there was a rapid deterioration with decrease of oxygen saturation and arterial pO2 values. Tolazoline induces a dilatation of the pulmonary vascular system by stimulating H1 and H2 receptors. Blocking of H2 receptors by cimetidine abolishes the effect of tolazoline at least partially. Our case shows that the interaction between tolazoline and cimetidine is of clinical significance. The recommendation to use cimetidine as prophylaxis against gastrointestinal side-effects induced by tolazoline can no longer be maintained. PMID- 8487791 TI - [Hemimegalencephaly. Therapy with hemispherectomy]. AB - Hemimegalencephaly is associated with a poor clinical course characterized by intractable seizures and severe encephalopathy. We present a case report of a girl with hemimegalencephaly. At the age of 9 month hemispherectomy was undertaken to preserve function of the other hemisphere. MRI and histologic examinations showed characteristic dysplastic malformations. Follow-up and the complications are described. PMID- 8487792 TI - [Secondary rhabdomyolysis and acute renal failure in gastroenteritis with hypernatremic dehydration]. AB - A child with severe gastroenteritis developed acute rhabdomyolysis combined with acute renal failure. The pathophysiological mechanisms of this clinical syndrome are not completely understood. Rhabdomyolysis is mainly due to osmotic changes on both sides of the cell membrane. The preventive and therapeutic measures consist of adequate fluid substitution, correction of electrolyte and acid-base imbalances, administration of diuretics and alkalization of the urine. Dialysis treatment may be necessary. In this particular case renal failure resolved but the child died of other organ failure. PMID- 8487794 TI - [Sexual abuse of children. A regional study of the prevalence and characteristics]. AB - BACKGROUND: In contrast to angloamerican countries there are no national figures for the incidence and prevalence of sexual abuse in Germany. Reports based on criminal statistics are inappropriate and are often misinterpreted. METHODS: In this report we present the main results of a regional study of the prevalence of sexual abuse in childhood and compare them with angloamerican studies. RESULTS: Based on replies from 1009 students and apprentices (age > 18y) the prevalence for criminal sexual abuse was found to be 25.2% for females and 6.2% for males. A breakdown of these figures showed that females reported having to experience anal, oral or sexual intercourse (2.3%), physical contact (11.7%), exhibitionism (4.6%) and other sexual behaviour without physical contact (6.6%). For males the prevalence rates for these categories of sexual abuse were 1.5%, 2.4%, 0.9% and 1.5% respectively. All these figures, especially those for males, should be evaluated critically as actual prevalence rates are probably higher. Girls, particularly those aged 6-10 years, are more often involved than boys. Ninety percent of physical abuse happens with persons known to the victim (60% within the family, only 8% with strangers. In general 95% of abusers are male, however in 25% of cases of hands-on-contact with boys the abusers are female. From the relative frequency of reported abuse we estimate the potential incidence to be 1:30 within the family, 1:23 with other acquaintances and 1:6 with strangers. CONCLUSIONS: The importance of regional differences should not be underestimated. These results cannot be generalized for the whole of Germany. Only prevalence studies appropriately reflect the scale of the problem; they are necessary for a broad, a rational and a sufficient planning of strategies designed for prevention, intervention and rehabilitation. More scientifically based epidemiological studies on the extend of sexual abuse are required in Germany. PMID- 8487793 TI - [Aspects of long-term management of children with myelomeningocele. Analysis of the last 10 years from the neuropediatric-neurosurgical viewpoint]. AB - BACKGROUND: Both the use of a selective policy of treatment of newborns with myelomeningocele and the right time of back closure are still controversially discussed. We report our experiences in the long-term care of children with myelomeningocele. METHODS: 103 newborns with myelomeningocele (n = 94) and meningocele (n = 9) born 1980 to 1990 and cared for regularly at the Olgahospital's pediatric clinic were followed up from the neuropediatric neurosurgical point of view. Postpartum we predominantly practised a selective policy of treatment. RESULTS: 15 of 21 children (71.4%) not operated on died during the first days or months of life, 6 (28.6%) survived. 70 were operated selectively, of which 9 (12.9%) died, 61 (87.1%) survived with mainly good result. There were no differences in the survival rate and frequency/type of postoperative complications with respect to the time of the back closure. 31 children with myelomeningocele (33%) had CNS anomalies other than the Arnold Chiari-Malformation, mostly being a dys- or aplasia of the corpus callosum and a deformed ventricle system. These were diagnosed almost exclusively by CT or MRT scan. CONCLUSIONS: We still predominantly practised a selective policy of treatment of newborns with myelomeningocele with mainly good results. PMID- 8487795 TI - [Bronchial asthma in childhood and adolescence. Burden of illness and coping with the disease]. AB - We report an empirical study in which the subjective complaints and stress experiences of children with bronchial asthma (outpatient, short- and long-term rehabilitation) are analyzed. The data were taken from a specifically developed questionnaire. The results should contribute to the conceptualization of programs for patient education and asthma training in order to meet the exact requirements and needs of the children to be instructed. The role of emotional asthma triggers is specified. Hierarchical cluster analysis is applied in order to analyze, first, the perception patterns of attack precursors and, second, the array of stressors that a child has to face as a consequence of suffering chronic asthma. Based on the social learning theory approach, the child's various expectations about the controllability of an asthma attack are differentiated. A factor analysis reveals that the coping process can be described by two basic coping dimensions. PMID- 8487797 TI - [Pneumologic aspects of mucoviscidosis]. PMID- 8487796 TI - [Reduction of pain perception of chronically ill children by intermittent infusion therapy]. AB - Chronically ill children who require life-long i.v. infusions in regular intervals (i.e. Agammaglobulinemia, HIV-infection) can be traumatized by such painful procedures. Some children gradually accept such infusions, whereas other children become sensitized and react with increasing fear and resistance. We report on our experience with a combined method of local anaesthesia and active role-plays enacting the i.v. infusion on a puppet. In more than 230 applications (approximately 11 per child) in our outpatient clinic, 19/20 children reported significantly less pain sensations after the 2nd or 3rd application. The children learned to handle actively the threatening situation. The method of local anaesthesia with Lidocaine/Prilocaine and role playing is suitable to relieve pain and reduces distress of such invasive events as regular i.v. infusions are. PMID- 8487798 TI - [The child and the environment. Position of the Academy of Pediatrics and Adolescent Medicine at the Klausurtagung 5-7 February 1993]. PMID- 8487799 TI - [Responsibilities, structure and organization of metabolic centers and special diagnostic laboratories. Position of the Professional Society of Pediatric Metabolic Disorders e. V]. PMID- 8487800 TI - [Declaration of Saint Vincent: management of diabetes and research in Europe]. PMID- 8487801 TI - Transforming growth factor beta as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. AB - BACKGROUND: Hepatic veno-occlusive disease and idiopathic interstitial pneumonitis are major causes of morbidity and mortality after bone marrow transplantation. Fibrosis is a characteristic of both conditions, and transforming growth factor beta (TGF beta) has been implicated in the pathogenesis of fibrosis. METHODS: Using acid-ethanol extraction to remove TGF beta from human plasma and a mink-lung epithelial-cell growth-inhibition assay to measure TGF beta activity, we quantified plasma TGF beta in 10 normal subjects and 41 patients before and after they underwent high-dose chemotherapy and autologous bone marrow transplantation for advanced breast cancer. RESULTS: There was no difference in pretransplantation TGF beta levels between the controls and the patients who did not have hepatic veno-occlusive disease or idiopathic interstitial pneumonitis after transplantation. In contrast, pretransplantation TGF beta levels were significantly higher in patients in whom hepatic veno occlusive disease or idiopathic interstitial pneumonitis developed than in the controls or the patients without these conditions. The predictive value for the development of either condition was 90 percent or more when pretransplantation plasma TGF beta levels were more than 2 SD above the mean established in the controls. CONCLUSIONS: The plasma TGF beta concentration measured after induction chemotherapy but before high-dose chemotherapy and autologous bone marrow transplantation strongly correlates with the risk of hepatic veno-occlusive disease and idiopathic interstitial pneumonitis after these treatments. PMID- 8487802 TI - Brief report: stenting of the ductus arteriosus as a bridge to cardiac transplantation in infants with the hypoplastic left-heart syndrome. PMID- 8487803 TI - Shattuck Lecture--misconduct in medical research. PMID- 8487804 TI - Hunting for the cause: how far to go? PMID- 8487805 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 22-1993. A 22-year-old man with 20 months of progressive swelling of the face. PMID- 8487806 TI - The diagnosis of thoracic aortic dissection by noninvasive imaging procedures. PMID- 8487807 TI - The diagnosis of thoracic aortic dissection by noninvasive imaging procedures. PMID- 8487808 TI - Cardiopulmonary resuscitation. PMID- 8487809 TI - Cardiopulmonary resuscitation. PMID- 8487810 TI - Cardiopulmonary resuscitation. PMID- 8487811 TI - Asthma. PMID- 8487812 TI - Asthma. PMID- 8487813 TI - Asthma. PMID- 8487814 TI - Felbamate therapy in the Lennox-Gastaut syndrome. PMID- 8487815 TI - Vitamins to prevent neural-tube defects. PMID- 8487816 TI - Case 46-1992: correction. PMID- 8487817 TI - Case 46-1992: correction. PMID- 8487818 TI - National Leadership Coalition's Plan for Health Care Reform. PMID- 8487819 TI - National Leadership Coalition's Plan for Health Care Reform. PMID- 8487820 TI - National Leadership Coalition's Plan for Health Care Reform. PMID- 8487821 TI - Reuse of a transplanted kidney. PMID- 8487822 TI - The spring meetings-- are they dying? PMID- 8487823 TI - A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease. AB - BACKGROUND: Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding. METHODS: We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density. RESULTS: Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen. CONCLUSIONS: Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea. PMID- 8487824 TI - Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. AB - BACKGROUND: A group of patients has been described who have chest pain resembling angina and positive exercise tests, but normal coronary angiograms and no coronary-artery spasm. This constellation of features has sometimes been called syndrome X or microvascular angina. We attempted to determine whether endothelium dependent vasodilatation of the coronary vasculature was impaired in patients with this syndrome. METHODS: We infused the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilators papaverine and isosorbide dinitrate into the left coronary artery of 9 patients and 10 control subjects. The diameter of the left anterior descending coronary artery was assessed by quantitative angiography, and changes in coronary blood flow were estimated with the use of an intracoronary Doppler catheter. RESULTS: Acetylcholine, given in doses of 1, 3, 10, and 30 micrograms per minute, increased coronary blood flow in a dose-dependent manner in both groups. However, the mean (+/- SD) acetylcholine-induced increases in coronary blood flow were significantly less (P < 0.001) in the patient (8 +/- 14, 37 +/- 37, 59 +/- 67, and 103 +/- 77 percent, respectively) than in the controls (62 +/- 52, 186 +/- 93, 341 +/- 128, and 345 +/- 78 percent, respectively). The changes in coronary blood flow in response to 2 mg of isosorbide dinitrate (236 +/- 66 percent vs. 280 +/- 56 percent) and 10 mg of papaverine (366 +/- 168 percent vs. 411 +/- 92 percent) did not differ significantly between the patients and controls. The administration of papaverine resulted in myocardial lactate production in the patients but not in the controls. The three lower doses of acetylcholine caused a similar degree of dilatation of the left anterior descending coronary artery in the two groups, and the highest dose caused a similar degree of constriction in the two groups. Isosorbide dinitrate and papaverine caused a similar degree of dilatation in both groups. CONCLUSIONS: These findings suggest that endothelium dependent dilatation of the resistance coronary arteries is defective in patients with anginal chest pain and normal coronary arteries, which may contribute to the altered regulation of myocardial perfusion in these patients. PMID- 8487825 TI - Association between exposure to environmental tobacco smoke and exacerbations of asthma in children. AB - BACKGROUND: Exposure to environmental tobacco smoke, as reported by parents, has been linked to diminished pulmonary function and more frequent exacerbations of asthma in children with the disease. Further insight into this association might be gained by using urine cotinine levels to measure actual exposure. METHODS: We measured urine cotinine levels in 199 children with asthma; 145 also underwent pulmonary-function studies. A parent answered questions about each child's exposure to environmental tobacco smoke. Acute exacerbations of asthma during the preceding year were documented through blinded review of medical records. Possible confounding factors were accounted for by the use of multivariate analysis and by comparisons of serum theophylline levels in exposed and unexposed children. RESULTS: The median urine cotinine levels were 5.6 ng per milliliter in the 116 children reported not to have been exposed to tobacco smoke, 13.1 ng per milliliter in the 53 children exposed to cigarette smoking by the mother or other persons, and 55.8 ng per milliliter in the 30 children exposed to cigarette smoking by the mother and other persons. Acute exacerbations of asthma increased with exposure, whether such exposure was reported by a parent or identified on the basis of the cotinine level; the relative risks for the highest as compared with the lowest exposure category were 1.8 (95 percent confidence interval, 1.4 to 2.2) for reported exposure and 1.7 (95 percent confidence interval, 1.4 to 2.1) for exposure indicated by cotinine levels. The forced expiratory volume in one second (FEV1), the forced expiratory flow between 25 and 75 percent of vital capacity, and the ratio of FEV1 to forced vital capacity also decreased with increases in both measures of exposure. CONCLUSIONS: Measurement of urine cotinine levels provides further evidence of an association between exposure to environmental tobacco smoke and pulmonary morbidity in children with asthma. These data emphasize the need for systematic, persistent efforts to stop the exposure of children with asthma to environmental tobacco smoke. PMID- 8487826 TI - Cutaneous disease and drug reactions in HIV infection. AB - BACKGROUND: Skin diseases, including adverse reactions to drugs, are thought to be more common among patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) than among other persons. These skin conditions can be disabling or disfiguring and may require discontinuation of essential drugs. METHODS: We identified 684 HIV-infected members of a 265,000 member health maintenance organization and reviewed their medical records to determine the frequency of dermatologic diagnoses from April 1, 1988, through January 15, 1991. We compared the rates of visits per year for skin conditions by HIV-infected men, 20 to 49 years of age, with those by non-HIV-infected men. We used an automated prescription data base to quantify exposures to drugs. RESULTS: Of the 684 HIV-infected patients, 540 (79 percent) were given one or more dermatologic diagnoses, for a total of 2281 diagnoses, including 188 cutaneous reactions to drugs. There were 43 hospitalizations for cellulitis (n = 15), cutaneous drug reactions (n = 13), or other skin problems. As compared with non HIV-infected men, the men with AIDS had visit rates that were at least 5 times higher for 18 of the 20 most common infectious and inflammatory skin conditions and at least 15 times higher for 9 conditions. Drugs with the highest rate of cutaneous reactions (per 1000 courses) included trimethoprim-sulfamethoxazole (149), sulfadiazine (200), trimethoprim-dapsone (156), and aminopenicillins (93). The number of diagnoses of skin conditions increased according to the stage of disease: it was lowest in patients immediately before the documentation of HIV infection and highest in patients with a diagnosis of AIDS. CONCLUSIONS: Cutaneous diseases, including drug reactions, are extremely common in patients with HIV infection, and their incidence increases as immune function deteriorates. PMID- 8487827 TI - Long-term complications of diabetes mellitus. PMID- 8487828 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 23-1993. A 30-year-old man with a dry cough, dyspnea, and nodular pulmonary lesions. PMID- 8487829 TI - Can bismuth improve the simple solution for diarrhea? PMID- 8487830 TI - Chest pain with normal coronary angiograms. PMID- 8487831 TI - The hazards of passive- and active-smoking. PMID- 8487832 TI - Prenatal diagnosis. PMID- 8487833 TI - Prenatal diagnosis. PMID- 8487834 TI - Prenatal diagnosis. PMID- 8487835 TI - Prenatal diagnosis. PMID- 8487836 TI - Acute bacterial meningitis in adults. PMID- 8487837 TI - Chronic idiopathic diarrhea. PMID- 8487838 TI - Acute myocarditis masquerading as acute myocardial infarction. PMID- 8487840 TI - More on routine HIV screening. PMID- 8487839 TI - Protective effect or symptomatic effect of deprenyl? PMID- 8487841 TI - More on routine HIV screening. PMID- 8487842 TI - More on office-based testing for HIV. PMID- 8487843 TI - Management of the nursing function. PMID- 8487845 TI - Psychiatric nursing. Amaudo--the village of peace. PMID- 8487844 TI - Psychiatric nursing. The Cuba experience. PMID- 8487846 TI - The development of professional nursing education 1860-1988. Part IV: South Africa. PMID- 8487847 TI - Equipment-related infection risks--the fibrescope. PMID- 8487848 TI - NPPHC/SAHSSO National Health Policy Conference. PMID- 8487849 TI - Supporting the care-givers in oncology. PMID- 8487850 TI - Respect and reverence for life. PMID- 8487851 TI - AIDS and the cycle of poverty. PMID- 8487852 TI - US Army to use peer review in breast cancer programme. PMID- 8487853 TI - US companies settle EPO patent suit. PMID- 8487855 TI - Differential salary scales. PMID- 8487854 TI - Beating fraud. PMID- 8487856 TI - Differential salary scales. PMID- 8487857 TI - Stifling the media. PMID- 8487858 TI - How and why of vesicle formation. PMID- 8487859 TI - Immunology. The power of clonal selection. PMID- 8487860 TI - Neurobiology. Motor neurons find their factors. PMID- 8487861 TI - World population forecasts. PMID- 8487862 TI - Primate origins: plugging the gaps. AB - Recent discoveries of fossil primate specimens have produced several surprises and challenged prevailing views of early primate evolution. Plesiadapiformes, long regarded as 'archaic primates', may perhaps be linked to the peculiar colugos instead. Inferred relationships of the earliest known undoubted primates (adapids and omomyids) are in turmoil. Both groups have been proposed as sources for the simian primates. Although the origin of the simian primates is obscure, new fossil evidence could push it further back by at least 10 million years. Such uncertainties reflect the low sampling level of the primate fossil record, which can potentially also lead to underestimation of times of origin within the primate tree. PMID- 8487863 TI - Antisense oligodeoxynucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. AB - The excitatory amino acid, L-glutamate, acting through its N-methyl-D-aspartate (NMDA) receptor, may contribute to neuronal death following cerebral vascular occlusion. In support of this hypothesis, NMDA receptor antagonists reduce the volume of infarction produced by occlusion of the middle cerebral artery in vivo and attenuate Ca2+ influx and neuronal death elicited by L-glutamate or NMDA in vitro. A complementary DNA coding for a major component of the NMDA receptor channel complex, a single protein of M(r) 105.5K (NMDA-R1), has been isolated from rat brain. Here we demonstrate that inhibition of the synthesis of NMDA-R1 by treatment with antisense oligodeoxynucleotides selectively reduces the expression of NMDA receptors, prevents the neurotoxicity elicited by NMDA in vitro and reduces the volume of the focal ischaemic infarction produced by occlusion of the middle cerebral artery in the rat. PMID- 8487864 TI - Neurotrophins promote motor neuron survival and are present in embryonic limb bud. AB - Embryonic spinal motor neurons are thought to depend for survival on unidentified factors secreted both by their peripheral targets and by cells within the central nervous system. The neurotrophins are a family of polypeptides required for survival of discrete central and peripheral neuronal populations in vivo and in vitro. In spite of their ability to reduce motor neuron death in vivo, the known neurotrophins have been thought to be without direct effect on motor neurons. Here we show that picomolar concentrations of three of them, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-5, can prevent the death of cultured embryonic rat spinal motor neurons. Furthermore, messenger RNA coding for neurotrophins is present at appropriate stages in spinal cord and limb bud, and mRNA for their receptors is found in motor neurons. These neurotrophins may therefore be physiological motor neuron growth factors. PMID- 8487865 TI - Affinity maturation leads to differential expression of multiple copies of a kappa light-chain transgene. AB - Transgenic animals containing rearranged heavy or light chains are used to study the process of hypermutation, which characterizes the maturation of the antibody response. LK6 mice contain five copies of a transgene coding for a light chain produced in response to the hapten 2-phenyloxazolone. We have selected hybridomas from secondary responses that express the transgene as the only light chain. Some of these hybridomas contain transgene copies carrying mutations known to improve antibody affinity. We have analysed the expression of the five transgene copies in those hybridomas. We report here that the somatic hypermutation process can affect the successful expression of antibody light-chain transgenes. When mutations that improve the antibody affinity appear in one transgene copy, antigenic selection favours cells that downregulate the other copies at multiple levels of gene expression, including examples where nonsense mutations correlate with a drop in messenger RNA level. PMID- 8487866 TI - NMR structure of a receptor-bound G-protein peptide. AB - Heterotrimeric GTP-binding proteins (G proteins) regulate cellular activity by coupling to hormone or sensory receptors. Stimulated receptors catalyse the release of GDP from G protein alpha-subunits and GTP bound to the empty alpha subunits provides signals that control effectors such as adenylyl cyclases, phosphodiesterases, phospholipases and ion channels. Three cytoplasmic loops of the activated receptor are thought to interact with three sites on the heterotrimeric G protein to provide high-affinity interaction and catalyse G protein activation. The carboxyl terminus of the alpha-subunit is particularly important for interaction with the receptor. Here we study the structure of part of the active interface between the photon receptor rhodopsin and the G protein transducin, or Gt, using nuclear magnetic resonance. An 11-amino-acid peptide from the C terminus of the alpha-subunit of Gt (alpha t (340-350)) binds to rhodopsin and mimics the G protein in stabilizing its active form, metarhodopsin II. The peptide alpha t (340-350) binds to both excited and unexcited rhodopsin and conformational differences between the two bound forms suggest a mechanism for activation of G proteins by agonist-stimulated receptors. Insight into receptor-catalysed GDP release will have broad application because the GTP/GDP exchange and the intrinsic GTPase activity of GTP-binding proteins constitute a widespread regulatory mechanism. PMID- 8487867 TI - Spruce pollen as a source of increased radiocesium concentrations in air. PMID- 8487868 TI - There is no mitotic nor meiotic recombination in the Drosophila Y-chromosome. PMID- 8487869 TI - GT dinucleotide repeat polymorphisms in a polygynous ant, Leptothorax spinosior and their use for measurement of relatedness. PMID- 8487870 TI - This could be good. PMID- 8487871 TI - Preceptors' perceptions of a baccalaureate preceptorial experience. AB - A preceptor's perception of a baccalaureate preceptorial experience has implications for faculty, nursing service administrators, and clinical agency personnel as they select nurses to serve as preceptors. This article describes a specific preceptorial experience and presents data collected from 137 preceptors who participated. Data include descriptive information about the preceptors and an analysis of their responses to six questions about the experience. PMID- 8487872 TI - Ethical and policy implications for the allocation of health care services to elderly persons in rural America. PMID- 8487873 TI - Patients', nurses', and physicians' perceptions of nurses' caring behaviors. AB - The purpose of this study was to identify how patients, nurses and physicians in a coronary care setting rank the importance of different nurse behaviors related to caring. The study was descriptive and used Q Methodology characterized by a forced choice format and priority rankings. Analysis of the mean scores for each subset of subjects revealed two items within the top five for all three subgroups. Comparison of this studies findings with previous studies showed similarities among patient rankings but little agreement among nurses regarding what constitutes caring behavior. Implications for practice, administration, research and education are identified. PMID- 8487874 TI - Nurses on hospital IRBs: a critical voice in protecting human subjects. AB - The nature and extent of nurses' participation on hospital institutional review boards (IRBs) has not previously been investigated. This descriptive study provides some insights into the characteristics of nurses serving on IRBs and describes the IRBs on which they serve. The nurses are typically master's prepared nurse managers who have served as volunteer or appointed members of the IRB for an average of 2.67 years. The IRBs have an interdisciplinary membership, and differ widely in structure and procedure, but generally, they conform to the requirements specified in the National Research Act for IRBs. The findings of this study have implications for nursing administration, practice, research, and education. PMID- 8487875 TI - Situational supports and job stress: a correlational study. AB - This correlational study provides information for creating a nursing work environment that supports coping with stress. Questionnaire-generated data were collected from registered staff nurses (N = 538) in two urban, acute care hospitals. Results of multiple regression analysis indicated that situational support variables (autonomy, control over practice, group cohesion, substantive exchange, manager consideration) correlated inversely with job stress. Predictor variables and demographics explained 37% of the variance in situational job stress [F(13, 442) = 19.74, P < .001] and 28% of the variance in personal job stress [F(13, 442) = 13.03, P < .001]. The variables may serve as situational supports for nurses coping with job stress. PMID- 8487876 TI - An unsafe or unprofessional colleague: what's a nurse to do? PMID- 8487877 TI - Cherry Ames and the future of nursing in children's literature. PMID- 8487878 TI - Synergy in nursing: partners-in-practice. AB - Diminished numbers of bedside care providers and support personnel for registered nurses have contributed to declining self-fulfillment and an exodus from the profession. RNs are expected to provide knowledge-based, competent care, yet they may not have the support staff to achieve this outcome. Nurse extender systems have been introduced in hope of changing this situation. One such nurse extender program is founded on the belief that the development of a voluntary relationship between the RN and a support person will result in a productive, synergistic partnership. The development of this relationship and the impact of the partnership concept as it relates to clinical application are explored here. PMID- 8487879 TI - [Lumbar puncture and incarceration]. PMID- 8487880 TI - [Current therapy of acute promyelocytic leukemia using vitamin A derivatives]. PMID- 8487881 TI - [Vitamin A derivatives: potential prevention and therapy of solid tumors]. PMID- 8487882 TI - [Indications for lumbar puncture; shifts in diagnosis]. PMID- 8487883 TI - [Routine urodynamic studies is not indicated in children with enuresis]. AB - From January 1980 to January 1992, urodynamic examinations were performed in 339 enuretic children without constipation or anatomical or neurogenic causes of incontinence. Nocturnal enuresis was seen in 178 patients, 130 children suffered from nocturnal and diurnal enuresis, and 31 had only diurnal enuresis. M. detrusor instability was found in 44% of the children and 73% showed more than 15% reduction in functional bladder capacity. In 5% an infravesical obstruction was suspected on pressure-flowmetry and in 12% dysfunctional voiding was seen. Routine urodynamic studies are not indicated in children with enuresis. PMID- 8487884 TI - [Usefulness of a physical examination upon return from the tropics]. AB - This study was undertaken to determine the usefulness of medical check-ups after return from the tropics by retrospective analysis of the data of the outpatient clinic for tropical medicine and imported diseases of the University Hospital of Nijmegen. During the years 1986-1990, 379 persons who had returned from the tropics and who were asymptomatic were subjected to a medical check-up (this group comprised 32% of the total of 1190 patients seen in the clinic during this period). In 230 persons (61%) no abnormality was detected. In 101 persons (27%) one or more diagnoses were made which were related to their stay in the tropics. For three-quarters of them treatment was indicated (77 patients). In the remaining 48 persons (13%) diagnoses were made which were neither related to the tropics nor required treatment (e.g. mild varices or minor kyphoscoliosis). Such diagnoses did not contribute to the usefulness of a medical check-up. In 200 persons a chest X-ray was made, either because they had stayed in the tropics for more than 3 years, or had had close contacts with the local population or because abnormalities were suspected on the basis of history or physical examination. While four X-rays revealed significant pathology, in only one of these did the patient benefit from its detection (early pulmonary tuberculosis). We conclude from our study that a medical check-up after return from the tropics is justifiable. The duration of the stay in the tropics by itself is no indication for a chest X-ray.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487885 TI - [Prognostic significance of the histological classification and staging for patients with a malignant non-Hodgkin lymphoma]. AB - OBJECTIVE: To assess the prognostic significance of histological classification, grade and stage with regard to overall survival in patients with non-Hodgkin's lymphoma (NHL). DESIGN: Retrospective analysis. SETTING: University Hospital St Radboud, Nijmegen. METHOD: All consecutive 346 patients with NHL diagnosed in the period January 1978-December 1990 were included in this one-centre study. Recorded data included histological type according to the Kiel classification, histological grading according to the International Working Formulation (IWF), Ann Arbor stage, age, sex, tumour mass, number of extranodal sites, serum LDH and ESR. Grading according to the IWF was assessed retrospectively for those patients whose primary disease had been diagnosed before 1982. The observation period ended September 1st, 1991. Overall survival was calculated according to Kaplan Meier. The significance of the prognostic parameters was studied using both univariate and multivariate stepwise regression analysis. RESULTS: There were 209 men and 137 women with a median age of 56 years (range 15-85). No initial treatment was given to 8% of the patients. After a median follow-up of 52 months, 179 patients (52%) had died; the calculated median survival time was 49 months. Patients with low-grade NHL had a significantly better short-term prognosis than the remaining patients. Related to clinical stage, only patients with stage I disease had distinctly longer survival times than those with more advanced disease. Multivariate analysis revealed serum LDH, age, stage and histological classification to be the most important independent prognostic variables. CONCLUSION: Even in multivariate analysis, histological classification and Ann Arbor stage have prognostic significance with regard to overall survival in patients with NHL. However, serum LDH levels proved to be the most important prognostic parameter. PMID- 8487886 TI - [Primary treatment of acute promyelocytic leukemia using all-trans-retinoic acid]. AB - We describe the medical history of a 68-year-old woman with acute promyelocytic leukaemia. As primary treatment she received all-trans retinoic acid. For the major part this treatment could be given on an outpatient basis. After 60 days there was a complete remission of the leukaemia with disappearance of the characteristic cytogenetic abnormality t(15;17)(q22;q21). PMID- 8487887 TI - [Eye injuries in 'paintball'; a modern 'war injury']. AB - Paintball shooting is played with increasing frequency in the Netherlands. A bullet, filled with paint, shot at 60 m/sec can cause serious damage to the eye. All five patients seen in two years showed a hyphaema. Four out of five patients showed damage of the posterior pole, including vitreous haemorrhage, choroidal rupture, retinal detachment, and sub- or intraretinal haemorrhage. Three out of five patients incurred permanent visual loss, varying from 3/60 to 25/100. Adequate instruction of the participants in the game and proper use of the eye protector will be of help in preventing eye injuries. PMID- 8487888 TI - [Financing of health research. The National Rheuma Foundation]. PMID- 8487889 TI - [Pregnant and in specialist education]. PMID- 8487890 TI - [Favorable effect of hematopoietic stem cells isolated from blood on hematologic recovery following high-dose chemotherapy]. PMID- 8487891 TI - [The dynamic hip screw in medial femoral neck fractures: results in 51 patients]. PMID- 8487892 TI - [The dynamic hip screw in medial femoral neck fractures: results in 51 patients]. PMID- 8487893 TI - [The dynamic hip screw in medial femoral neck fractures: results in 51 patients]. PMID- 8487894 TI - [The dynamic hip screw in medial femoral neck fractures: results in 51 patients]. PMID- 8487895 TI - [Oral rehydration therapy]. PMID- 8487896 TI - [Controversies in preventive health care. IV. Primary health care]. PMID- 8487897 TI - [A patient's complaints due to inadequacies in communication]. PMID- 8487898 TI - [Prevention of vitamin D deficiency in adults; at what age should it start and with what dosage?]. PMID- 8487899 TI - [Late intestinal radiation injuries; diagnosis and treatment]. PMID- 8487900 TI - [Good results of 100% oxygen treatment for acute carbon monoxide poisoning; temporarily no indication for hyperbaric oxygenation]. AB - OBJECTIVE: To describe the complications in patients with acute carbon monoxide intoxication, if treated with 100% instead of hyperbaric oxygen. DESIGN: Retrospective chart review. PATIENTS: Thirty-three patients with acute-carbon monoxide intoxication admitted to the medical Intensive Care Unit of Leiden University Hospital. RESULTS: The mean carbon monoxide level of all patients was 29.4%. Ten patients had a carbon monoxide level above 40%. Seven patients (21%) were in coma on admission. Most complications occurred in the latter group. All patients were treated with normobaric 100% oxygen. Recovery was usually rapid. No patient showed neurological deficits at discharge. CONCLUSION: The short-term prognosis of patients with acute carbon monoxide intoxication is good, even if they are not treated with hyperbaric oxygen. There is still inconclusive evidence from the literature that hyperbaric oxygen improves the prognosis in these patients. PMID- 8487901 TI - [The significance of endometrial cells in the cervical smear]. AB - Presence of atypical endometrial cells in a cervical smear is quite unusual; but if they are found the woman needs extra attention because of the risk of adenocarcinoma of the uterus. Postmenopausal women sometimes also have endometrial cells without atypia in the cervical smear, as a sign of endometrial pathology. We conducted a retrospective follow-up study of these women. From 1978 to 1989, 52 smears from a total of about 50,000 postmenopausal women were classified as Pap IIIA, due to the presence of normal endometrial cells. Histological follow-up was performed in 25 cases and 3 times an adenocarcinoma of the endometrium was diagnosed (6%). The smears from 142 women (pre- and postmenopausal) contained atypical endometrial cells and therefore were classified as Pap IIIA or higher. Histological follow-up was performed in 104 cases. In 48% (n = 68) an adenocarcinoma was diagnosed. In 75% of these cases (n = 51) the atypical cells were graded as severe or worse (> or = Pap IIIB). Cervical smears are not taken to detect pathology of the endometrium, but whenever atypical cells are found in the smear there is a strong indication for further (gynaecological) examination. PMID- 8487902 TI - [Parametrial coitus]. AB - We saw an 18-year-old female patient with a practically imperforated and thickened hymen who, during an attempt at intercourse, suffered traumatic penetration in the right parametrium, parallel to the vagina. The hymen was opened further. The girl recovered completely. PMID- 8487903 TI - [Are extensions of the Dutch vaccination program to be expected?]. PMID- 8487904 TI - [Hemodilution to measure in acute brain infarct using a 20% albumin solution and physiological saline]. PMID- 8487905 TI - [Continuation or discontinuation of life-support measures in newborn infants]. PMID- 8487906 TI - [Continuation or discontinuation of life support measures in newborn infants]. PMID- 8487907 TI - [Where are laboratory studies in clinical-pharmaceutical research conducted? Medical-ethical considerations]. PMID- 8487908 TI - [Vasectomy and prostate cancer; education and practical advice]. PMID- 8487909 TI - [A patient with hypocalcemia: an experiment of nature and culture]. PMID- 8487910 TI - "Doctors unchecked"--the apology of a physician. PMID- 8487911 TI - "Parvovirus B-19 infection in pregnancy: two case reports and discussion". PMID- 8487912 TI - Open tibia fractures. AB - Open tibia fractures can be very challenging fractures to care for. Good results should be expected, however, if a thorough irrigation and debridement is performed, repeated as necessary, and appropriate antibiotics utilized. Soft tissue coverage is extremely important in open tibia fractures to decrease the rate of infection and to facilitate fracture healing. Bony stabilization can be achieved in a variety of ways. In the past, the gold standard has been external fixation. In the future, however, small, unreamed, locked intramedullary nails may be utilized more frequently, especially with Types I, II and IIIA open tibia fractures. PMID- 8487913 TI - Necrotizing enterocolitis. AB - In summary, NEC is the most common gastrointestinal emergency in the newborn. Premature infants are the most likely affected. Although progress has been made in elucidating some of the factors responsible for NEC, the exact etiology is still unclear. Aggressive medical management is required, but indications for surgical intervention differ from institution to institution. Overall mortality remains about 20% to 40%. About one half of survivors seem to have no sequelae, but the remaining infants may have significant ones which require additional surgical intervention or produce life long problems. Efforts at prevention have not been very successful. The single most important prophylactic measure would be to prevent prematurity. Until the exact pathogenesis of NEC is better understood, effective preventive measures are unlikely to be developed. PMID- 8487914 TI - BDNF and trkB mRNA expression in the hippocampal formation of aging rats. AB - Quantitative in situ hybridization and northern blot analysis techniques were used to determine the topographical distribution and levels of mRNA coding for brain-derived neurotrophic factor (BDNF) and the tyrosine receptor kinase (trkB) mRNA in the hippocampal formation of two strains of male rat during aging. Age did not change the prevalence or regional distribution patterns of BDNF or trkB mRNA in the hippocampal formation throughout the lifespan of male Sprague-Dawley rats. There also were no significant differences in the prevalence or topographical distribution patterns of trkB mRNA transcripts during aging. Northern blot analysis of hippocampal RNA from male Fischer 344 confirmed that neither BDNF mRNA nor trkB mRNA levels changed with age. These findings suggest that age-related neurodegenerative changes, including the atrophy of the cholinergic septo-hippocampal pathway, are not the result of changes in hippocampal BDNF or trkB mRNA expression. Moreover, the prevalence and distribution of synaptosomal-associated protein 25 (SNAP-25), a neuron-specific protein located in synaptic terminals and a putative marker of synaptic integrity, did not change with age. These findings indicate that altered hippocampal synaptic plasticity which occurs in the aged rat brain is not a reflection of changes in the expression of BDNF or trkB receptor mRNA. PMID- 8487915 TI - Response properties in young and old Fischer-344 rat lateral superior olive neurons: a quantitative approach. AB - Significant age-related functional deficits may result from a selective loss of inhibitory processing in the lateral superior olivary (LSO) nucleus. To test this hypothesis, methods were developed for quantitative comparisons of the excitation evoked by ipsilateral acoustic stimuli and the inhibition evoked by contralateral acoustic stimuli in neurons recorded from this binaural structure. Data were obtained from 103 LSO neurons from 22 young adult (3-6 month) and 70 LSO neurons from 14 old (20-23 month) Fischer-344 (F-344) rats. Age-related increases in the thresholds of auditory brainstem responses as well as in the inhibitory and excitatory responses of LSO neurons were observed. Spike-discharge rates were analyzed using multiple regression analysis for interaural intensity data and by calculating correlation coefficients between excitatory and inhibitory isointensity curves. Most LSO principal cells exhibited ipsilateral excitation and contralateral inhibition of similar strength for similar stimuli. Inhibitory and excitatory response areas of these neurons were similar based on visual inspection and correlation coefficients. No statistically significant age-related changes were observed for (a) rate-level functions generated by ipsilateral or contralateral stimuli; (b) maximal discharge rate; (c) conduction latencies; or (d) measures of binaural function. However, a small percentage of LSO neurons both in young and old rats displayed "unmatched" inhibitory and excitatory response areas. Quantitative methods developed in this study are used to examine age-related changes in binaural function in the inferior colliculus of F-344 rats and in the LSO of the Sprague-Dawley rat. Although no asymmetrical aging changes were observed for the F-344 rat LSO, there appear to be significant differences between the aging auditory system in the F-344 and Sprague-Dawley rats. Age related changes have been previously described for the F-344 in other brainstem auditory structures. PMID- 8487916 TI - Regional spectral analysis of the REM sleep EEG in mild to moderate Alzheimer's disease. AB - Regional spectral analyses of the EEG during wakefulness and REM sleep was performed in eight patients with mild to moderate Alzheimer's disease and compared to that of healthy age-matched controls. Alzheimer patients presented some EEG slowing in frontal, parieto-occipital and temporal regions in the waking state. However, this EEG slowing was much better revealed in REM sleep, whether expressed by the ratio of slow to fast frequencies or by changes in each of the frequency bands. Moreover, regional differences in EEG slowing, relatively nonexistent in the awake EEG, were a prominent feature of the REM sleep EEG. Importance of cholinergic basal forebrain in the desynchronization of the REM sleep EEG might explain these results because this structure is affected in early Alzheimer's disease. PMID- 8487917 TI - Continuous ICV infusion of scopolamine impairs sustained attention of rhesus monkeys. AB - Systemic administration of anticholinergic agents impairs cognitive performance in animals and man. The anticholinergic, scopolamine, has profound effects on peripheral and central cholinergic function, making interpretation of its effects on cognitive performance difficult. To circumvent this problem, scopolamine was administered directly to the central nervous system of rhesus monkeys using a subcutaneously implanted infusion pump connected to a cannulae directed toward the right lateral ventricle. Intracerebroventricular (ICV) infusion of scopolamine (0.004, 0.012, 12.5, and 40.0 micrograms/kg/h) produced a dose dependent decrease in the number of responses on a continuous performance task. Response decrements produced by scopolamine were seen mainly during the last half of the test session and at short stimulus durations. These data suggest that scopolamine produces a deficit in sustained attention or slowing of information processing that is mediated through direct central cholinergic blockade in the rhesus monkey. PMID- 8487918 TI - Age-related changes in footshock avoidance acquisition and retention in senescence accelerated mouse (SAM). AB - An inbred strain has been developed which exhibits some characteristics of aging in mice as young 6 months of age. The strain was designated "Senescence Accelerated Mouse" (SAM). A subline of the SAM strain, P/8, has an early onset of impaired learning in appetitive and aversive training tasks. Simple aversive and appetitive tasks were learned normally up to 12 months of age, whereas more difficult tasks detected impairment as early as 6 months of age while the mice still had good general health. Comparable impairment of learning and memory in C57BL/6Nnia mice was not detected until about 24 months of age which is near the end of the strain's lifespan when general health declines. In the present study, we report age-dependent impairment of acquisition and retention for footshock avoidance conditioning. Long-term (1 week) but not short-term (1 h) retention was adversely effected by aging. In 12-month-old P/8 mice, practicing the avoidance response (overtraining) did not alleviate the impairment of long-term memory processing. PMID- 8487919 TI - Age-related changes in the pharmacological improvement of retention in senescence accelerated mouse (SAM). AB - The P/8 line of the senescence accelerated mouse (SAM) model exhibits characteristics of aging early in its lifespan including an early onset of impaired learning and memory which becomes progressively worse with age. Age matched controls of the R/1 line do not show impaired learning and memory. We report age-related changes in the drug dosage needed to improve 1 week retention in the P/8 but not R/1 line. The results indicate that 8-month-old P/8 mice show a reduced sensitivity to memory enhancing doses of cholinomimetics and an increased sensitivity to a serotonin antagonist compared to 4-month-old mice. By 12 months of age, improvement of retention required still higher doses of cholinomimetics and even lower doses of the serotonin antagonist. Higher doses of an opioid antagonist and a dopamine agonist were needed to improve retention in 12-month-old mice. A GABA antagonist and an alpha noradrenergic agonist improved retention at the same dose in mice 4, 8, and 12 months of age. PMID- 8487920 TI - Geometric response to nerve growth factor is preserved in aged rat sensory neurons: a single-neuron culture study. AB - We previously established a single-neuron culture system to analyze the primary effects of neurotrophic factors and reported that NGF promoted neurite extension in young adult (4- to 6-month-old) rat dorsal root ganglion (DRG) neurons by promoting neurite arborization. In this study, we demonstrated that the effects of NGF on neurite regeneration in DRG neurons was well preserved in aged rats (20 to 24-month-old and 33-month-old). NGF did not increase the percent process bearing neurons in aged rats, which indicated that neuronal survival was not promoted by NGF, but it significantly enhanced the number of branching points, total neurite length, and soma size in aged neurons. These effects of NGF on neurite geometry tended to be reduced to some extent in aged neurons and the initiation of neurite-outgrowth in aged neurons was also delayed as compared with young adult neurons. NGF-responsive subpopulation of neurons, found in the entire range of neuronal size, were preserved in aged rats. These findings indicate that NGF could play an important role in regeneration of injured DRG neurons of aged animals. PMID- 8487921 TI - Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians. AB - beta A4 deposits occur in the brain of some individuals over 50 years of age. It could be a part of the aging process or indicate a disease found frequently in the elderly. To address this question, beta A4 immunocytochemistry was performed on the brain of 15 nondemented and 5 demented centenarians, some of whom were affected by Alzheimer's disease. We found beta A4 deposits in the parahippocampal and the superior temporal gyri of all the cases, whatever the clinical state. The hippocampus was frequently spared. The lesion density was not correlated with the severity of the mental deterioration. The constant deposition of beta A4 protein in the brain of very old people indicates that this process does not spare a large proportion of this population. This result favors beta A4 accumulation in the brain being an ineluctable age-related process. PMID- 8487922 TI - [Measurement of cerebral blood flow by stable xenon-enhanced computed tomography (series 3)]. PMID- 8487923 TI - [Continuous intracarotid infusion of mannitol in severe head injury]. AB - The clinical significance of continuous intracarotid infusion of a small dose of mannitol (ICI of mannitol) was discussed. Eighteen patients suffering from severe head injury with Glasgow coma scale (GCS) less than 6 were treated by ICI of mannitol for the improvement of raised intracranial pressure (ICP). In all of these 18 cases, conventional venous administration of mannitol could not be carried out, because of the unstable vital signs due to hypovolemic shock such as multiple trauma or disturbance of serum sodium and potassium levels. This method requires that a 20% mannitol solution be directly and continuously administered to the bilateral common carotid artery. The ICP 6 hours after the beginning of ICI of mannitol was significantly lower than the ICP just before the treatment. The total amount of excretion of the sodium and potassium through the urine every hour decreased significantly after this method was used. It was also noticed that this method was very suitable for stabilizing the vital signs in cases which had unstable vital signs such as hypovolemic shock. These findings suggested that ICI of mannitol has an advantage over the conventional venous administration of mannitol in cases which had to have correction of serum electrolyte or which had unstable vital signs. PMID- 8487924 TI - [Clinical assessment of meningeal carcinomatosis; from the viewpoint of the analysis of intracranial pressure]. AB - Meningeal carcinomatoses (MC) have been mainly studied from the viewpoint of the analysis of intracranial pressure (ICP). From the CT findings, ten patients were divided into two groups: group I, six patients showed characteristics of MC; group II, four showed normal characteristics. Ventricular fluid pressure (VFP) was continuously measured by a controlled ventricular drainage tube using a Spectramed P-10EZ at 3.1 +/- 2.1 months after the onset of the neurological symptoms. At the same time as VFP monitoring, the CBF by 133Xe method was measured in 5 cases and RI cisternography was performed in 9 cases. "A" wave was observed in 5 cases of group I and in 3 cases of group II. "B" wave was observed in all cases of both groups. In all 10 cases, the occurrence rate of both A and B waves (ORA, ORB) were high, averaging 2.34 +/- 0.54 times/hour, 74.0 +/- 16.6% time, respectively. Mean resting pressure(R) and mean peak pressure(P) tended to be high, averaging 28.8 +/- 12.2mmHg, 58.9 +/- 13.7mmHg, respectively. Mean cerebral perfusion pressure corresponding with R and P (CPPR, CPPP) was markedly reduced, averaging 79.1 +/- 15.9mmHg, 50.9 +/- 12.7mmHg, respectively. Both ORA and ORB in group I were higher, and both CPPR and CPPP in group 1 were lower, than in group II. Statistically, this is significant. Both R and P in Group I tended to be higher than in group II. This has no statistical significance. CBF in all 5 cases averaged 34.8 +/- 8.4ml/100g/min. No significant difference in the impairment of CBF was found between both groups. RI cisternography showed delayed clearance in all 9 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487925 TI - [Vasospasm and its outcome after early surgery for ruptured cerebral aneurysms: relationship with the clinical grade based on the Glasgow Coma Scale]. AB - Over a 9 year period, 270 patients who had early aneurysm surgery within 7 days after subarachnoid hemorrhage were analyzed regarding occurrence of vasospasm (VS) and its outcome. Occurrence of VS was recognized by ischemic neurological deterioration, with or without CT evidence of infarcts. Surgical outcome was assessed by the Glasgow Outcome Scale 6 months postoperatively. The results were correlated with age, aneurysm site, day of surgery, and preoperative clinical grade evaluated by the Glasgow Coma Scale (GCS). Thirty patients with the GCS sum score of less than 6 were excluded from the analysis of VS. Eighty two patients (34%) developed VS, of which 36 patients (15%) showed ischemic symptoms only, and 46 (19%) had infarct on CT. The incidence of symptomatic VS was 12% in GCS 15 group (117 patients), 23% in GCS 14-13 group (70 patients), and 11% in GCS 12-7 group (53 patients). That of VS with infarct was 14%, 23%, and 26% in GCS 15, GCS 14-13, and GCS 12-7 groups, respectively. Thus, there was a close correlation between the clinical grade based on the GCS and the incidence of VS, especially with infarct. The grade was also useful in predicting the surgical outcome. VS was more common in the older age group. The site of aneurysm or the day of surgery had no apparent influences on the incidence of VS or its outcome. Overall, the incidence of poor outcome due to VS proved to be 12%, which accounted for one-third of the cases in which there was poor outcome due to various causes. PMID- 8487926 TI - [The evaluation of tumor blood flow measured by single photon emission CT]. AB - The blood flow was measured in brain tumors (tumor blood flow: TBF). A total of 83 patients were studied. These included cases of 29 gliomas, 25 meningiomas, 10 metastatic brain tumors and others. Measurements of TBF were performed using the 133Xe gas inhalation technique, the N-isopropyl-p-[123I] iodoamphetamine intravenous injection method, and SPECT. The results showed that TBF was variable, and was higher in meningioma. There was a significant correlation between TBF and the number of vessels in the operative specimen. Higher TBF tumors had a tendency to bleed profusely during operation. IMP E1 images were closely similar to Xe-SPECT images in TBF value. In cases with glioma, moderate correlation was noted between Xe-SPECT and IMP E2 image. A discrepancy in TBF values between IMP E2 image and Xe-SPECT image was observed. There was low activity on IMP E2 image and high TBF value in Xe-SPECT image. This was true especially in cases with angioblastic meningioma. In conclusion, TBF was considered to be helpful not only for preoperative diagnosis, but also for estimation of bleeding from tumors during operation and treatment. PMID- 8487927 TI - [How to preserve the facial nerve in acoustic neurinoma excision: development of a microneurostimulator]. AB - We developed a Micro-neurostimulator that is suitable for intracranial electrical stimulation of the facial nerve in excision of acoustic neurinomas. The tips of our Micro-neurostimulator were thinner and finer than those of commercially available bipolar forceps and therefore it was possible to stimulate tumor tissue and the facial nerve selectively. This facilitated precise excision of tumor tissue from the facial nerve without residual tumor tissue around it. It was emphasized that the shape of the tips of stimulating electrodes and the stimulus intensity were the most important factors in obtaining reliable responses in preserving the facial nerve using intracranial electrical stimulation and evoked electromyographic responses. PMID- 8487928 TI - [Experimental study of acute spinal cord injury: a study of spinal blood flow]. AB - It is well known that the worsening of neurological findings after spinal cord injury is due to the secondary progression of pathological changes which may be caused by spinal cord blood flow disturbance. We measured spinal blood flow of 5mm rostrally and caudally distant portions from the injured point, using the laser Doppler flowmeter experimentally. Forty rats were used. Ten of these were used as a control group. And thirty animals were injured at the level of the tenth thoracic cord with a 50g epidural one minute compression method and measured continuously from 30 minutes before the injury to 6 hours after the injury. Twenty two surviving animals were evaluated. In the control group, spinal blood flow was stable. But in the injured group, spinal blood flow dropped by 30.6 + 9.8% on the rostral side and 37.3 + 17.6% on the caudal side in comparison with the resting value soon after the injury. Although the flow improved to 89.3 + 11.1 and 71.3 + 17.8% respectively 15 minutes later, it dropped again gradually and reached 42.8 + 14.1 and 66.2 + 16.4% respectively 6 hours after the injury had been inflicted. Lastly, in the animals, carbon perfusion was performed through the left ventricle. The normal figured vasculature in the preparation of the injured and measured portion was calculated with a microcomputer imaging analyzer and compared with control groups. The number of the normal vessels was significantly more abundant on the caudal side than on the rostral side (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487929 TI - [Percutaneous transluminal angioplasty for cervical internal carotid artery stenosis: case report]. AB - We encountered one case of right cervical internal carotid artery (ICA) stenosis with ulcerative plaque. The patient was treated using percutaneous transluminal angioplasty (PTA). A 70 year-old man complained of left motor weakness and left hemidysesthesia. CT scan on the day of admission showed no abnormal findings. Angiographical findings revealed a severe right ICA stenosis with ulcerative plaque. We first treated the patient conservatively because of high-positioned carotid bifurcation, bronchial asthma and hypertension. 20 hours after the stroke, left motor weakness gradually worsened and CT scan revealed multiple low density areas in the right fronto-parieto-occipital watershed region. Because of this, we treated the stenosed ICA by PTCA balloon dilatation catheter, and successfully obtained adequate dilatation with no complications. We propose that PTA of ICA stenosis, as well as PTA of the vertebral region, is a useful method for patients who have conditions which would make surgical operations risky. PMID- 8487930 TI - [Dumbbell cervical neurinomas with subcutaneous extension: report of two cases]. AB - Two cases of dumbbell cervical neurinomas with massive subcutaneous extension were reported. The first case was A 30-year-old woman who was admitted to our hospital because she had been aware of a left lateral cervical subcutaneous mass and was suffering from shoulder dullness. On admission, neurological examination revealed hypesthesia to touch and pain in the segmental area of C4, and hyperreflexia in the left biceps and patellar tendon reflexes. Plain X-ray showed enlargement of the left C3/4 intervertebral foramen. CT scan, post-myelogram CT and MRI demonstrated a dumbbell shaped tumor at the level of C3-4. Angiogram showed an anterior shift of the left vertebral artery (VA) and tumor stain. Temporary occlusion of the left VA by a balloon catheter was performed leaving no neurological deficits. The second case was a 36-year-old woman who had been aware of a left lateral cervical subcutaneous mass. She complained of shoulder pain and finger clumsiness. On admission, neurological examination revealed weakness of the left deltoid muscle, hypesthesia in the segmental area of C3-4 and exaggeration of all deep tendon reflexes in the left-side extremities. Plain X ray showed enlargement of the C2/3, C3/4 and C4/5 intervertebral foramina. CT scan, post myelogram CT and MRI demonstrated a dumbbell shaped tumor at the level of C2-5. Angiogram showed an anteromedial shift of the left VA and tumor stain. Temporary occlusion test of the left VA by a balloon catheter was performed with negative results. In each case two-stage operations were undertaken with excellent results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487931 TI - [Surgical excision of a huge olfactory groove meningioma by extensive transfrontal approach]. AB - A case with a huge olfactory groove meningioma was cured surgically by extensive transfrontal approach. A 46-year-old female was admitted with complains of left visual disturbance. CT revealed a large high-density mass in the base of the frontal fossa which was enhanced homogenously. Hyperostosis was seen in the planum sphenoidale. MRI showed a relatively low intensity with a peritumoral low intensity rim on T1WI and high intensity on T2WI. The brain stem had shifted dorsally. Rich feeding to the lesion from the ethmoidal artery was seen on angiography. An operation was performed using an extensive transfrontal approach. After bifrontal craniotomy, orbitofrontal osteotomy was performed. This approach enabled us to minimize frontal lobe retraction, to interrupt the blood supply to the tumor early, and to remove the tumor completely from the frontal base and to present invasion of the sinuses. The postoperative course was uneventful without cosmetic problems. PMID- 8487932 TI - [A case of cortical deafness with bilateral putaminal hemorrhage]. AB - A 56 years old right-handed female, a housewife, had suffered from right putaminal hemorrhage which had been treated surgically in July, 1985. Since it was difficult to approach the trans-sylvian fissure, evacuation of the hematoma was performed transcortically through the superior temporal gyrus. She was neurologically free and lived normally until she suddenly became completely deaf in April, 1991. On admission, she was alert, well oriented and spontaneously stated that she was deaf. She showed no response to verbal commands or loud noises but followed complex written commands. No other neurological deficit was observed. In addition to an irregular low-density area in the right temporal lobe, CT scan revealed a left putaminal hemorrhage. Audiological testing disclosed pure tone thresholds to be below 90db on both sides. Auditory brain stem response (ABR) showed waves I to VI in normal latency ranges, but wave VII was not observed. She was treated conservatively. Although her hearing loss had been gradually improving for 1 month, she suffered from word deafness, an inability to comprehend speech, for the following 2 months. Clinical features, CT findings as well as results of ABR suggest that hearing loss observed in this case, cortical deafness, was presumably due to bilateral damage of acoustic radiation of the temporal lobe. It was also suggested that, although she was asymptomatic, cortical and subcortical damage to the right temporal lobe following evacuation of the putaminal hematoma may have been extensive. During surgical procedures for evacuation of the putaminal hematoma, it has to be always kept in mind not to damage the auditory cortex and its radiations. PMID- 8487933 TI - The heightened sensitivity of hypophyseal cells of neonatal rats to corticosteroids. PMID- 8487934 TI - The morphofunctional state of the supraopticoneurohypophyseal system of rats in hypoparathyroidism. PMID- 8487935 TI - Structural changes of the human embryonal cortex during explantation. PMID- 8487936 TI - The serotoninergic innervation of the area postrema. PMID- 8487937 TI - The projections of the amygdaloid body and the dopaminergic mesencephalic formations to the dorsal and ventral pallidum of the cat brain. PMID- 8487938 TI - An hypothesis regarding the cortical mechanisms of operative memory. AB - Investigations of the neuronal activity of the cerebral cortex of monkeys during the performance of a delayed spatial choice made it possible to formulate an hypothesis regarding the neuronal systems providing for operative memory. One system functions on the principle of relay race-reverberation transmission of information. During the action of a sensory signal a population of spatially selective "sensory" neurons is excited. By the delay period (operative memory) this information is transmitted to a population of "memory" neurons. The delay period is quantized in time segments in the course of which individual populations of cells are involved in relays in the reverberation activity. Each of these populations comprises a "neuronal trap" in which the excitation circulates for 1.5-2 sec. At the end of the delay period switching of the excitation to a different population of cells takes place, which are associated with the preparation of a goal-directed movement (the "neurons of the motor programs"). Another system of neurons assures the reliability of the transitional phases of the above-named processes, specifically: 1) of the switchings of information from the "sensory" neurons to the "memory" neurons and subsequently to the neurons of the "motor programs"; 2) the reflection of the entire period of operative memory without relay race-reverberation; and 3) the preservation of the signal information in the activity of a unified neuronal population right up to the moment of the performance of the goal-directed movement. The above-designated systems are represented variously in the associative (frontal and parietal) zones of the neocortex. PMID- 8487939 TI - The participation of cortical areas of the brain in processes of the perception and reproduction of emotional states of man. AB - The participation of the cortical zones of the brain in the processes of the perception and reproduction of the emotional states of man was investigated by means of a new method of mapping intracortical interaction. During the recognition of emotions the focus of activity was in the left temporal area of the cortex. If the emotions were not recognized, a focus of activity was not observed in the temporal area of the cortex, but was found in the frontal divisions of both hemispheres. Foci of activity were observed primarily in the frontal areas of the cortex during the mental reproduction of emotional states. PMID- 8487940 TI - A computer analysis of EEG-intersignal reactions during the development of motoric alimentary conditioned reflexes in dogs. AB - The background electrical activity of the neocortex in the interstimulus periods at the stage of generalization during the development of alimentary motor conditioned reflexes (CR) in dogs was the investigational object. It was characterized by the appearance of brief (0.1-0.3 sec) trains of high frequencies (HF), significantly exceeding the adjacent initial baseline in frequency and amplitude. The relative variance index which we had developed made it possible to distinguish this EEG phenomenon in the initial realizations of the background activity when they were inputted into a digital computer. It was not possible to evaluate the parameters of the HF chains by means of a spectral correlation analysis. Nonstandard techniques of computer analysis directed toward the decomposition of the EEG tracing into a system of oscillations and toward the obtaining of the corresponding amplitude-frequency distributions (maps) were developed by us for the purpose of accomplishing this objective. It was demonstrated that HF trains were localized in these maps in specific, quite compact regions. PMID- 8487941 TI - The influence of high-frequency stimulation of the midbrain reticular formation on the interaction of neurons of the neocortex. AB - The influence of the stimulation of the midbrain reticular formation (NRT) at a frequency of 75-100 Hz, current strength 33-400 microA, on the interaction of neurons of the visual and sensorimotor areas of the neocortex of rabbits was investigated. Cross- and autocorrelation histograms of the impulse sequences were plotted. Stimulation of the NRT led to an increase in the number of pairs of neurons functioning in correlation and an increase in the probability of discharges of neurons one after the other with delays from 100 to 400 msec as compared with resting wakefulness. The mechanisms of the interaction of the cells were not altered in the process. Comparison with previously obtained data made it possible to conclude that activation of the NRT may lead to specific changes in the interaction of neurons which are observable during pseudoconditioning and at the beginning of the development of a conditioned reflex. PMID- 8487942 TI - The intercentral relationships of rabbit brain biopotentials during the creation of a blink dominant. AB - The intercentral relationships of the biopotentials of the sensorimotor area of the cerebral cortex, the ventroposteromedial nucleus of the thalamus, and the motor nucleus of the oculomotor nerve during the formation of a blink dominant, created by means of serial stimulation of one eye by an airstream, were investigated in chronic experiments on rabbits by the spectral correlation analysis method. An increase in the power of the spectrum and an increase in the COH of the potentials of the delta range were identified in structures associated with the function of the blinking of the stimulated eye. Analogous reorganizations of biopotentials were identified in a dominant focus arising by induction of the symmetrical center of the other eye. PMID- 8487943 TI - Cholinosensitivity as an indicator of functional differences of neurons of the cortex of young and old rabbits. AB - The cholinosensitivity of neurons of the motor cortex of young and old rabbits was studied. It was shown that muscarinic activation in the cells of old animals is encountered half as often than in young animals. The age-related decrease in cholinosensitivity is explained by an insufficiency of the overall activation of neurons in old animals. The change in the functional state of the cells of the motor cortex leads to the fact that the frequency of impulse activity of neurons associated with movement proves to be insufficient for the achievement of effective cortical control of motor functions. PMID- 8487944 TI - The reactions of neurons of the sensorimotor cortex of rabbits to stimulations of various sensory modalities against the background of the action of actinomycin D, a protein synthesis blocker. PMID- 8487945 TI - The influence of antibodies to brain-specific nonhistone chromatin proteins on the development and reproduction of a passive avoidance conditioned reflex in rats. PMID- 8487946 TI - NADPH-diaphorase histochemistry identifies isolated endothelial cells at sites of traumatic injury in the adult rat brain. AB - In addition to labelling endothelium, some ependymal cells (including tanycytes), and a subpopulation of neurons, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry of stab lesion sites in the neocortex revealed a large population of cells concentrated within several hundred micrometers of the lesion site. To determine the identity of these cells, NADPH-diaphorase reactivity was compared to binding with either the I-B4 isolectin from Bandeiraea simplicifolia (which has previously been shown to identify endothelial cells and activated mononuclear phagocytes), or a monoclonal antibody (OX-42) that recognizes activated mononuclear phagocytes. Many I-B4 lectin-labelled cells were also NADPH-diaphorase reactive, and other I-B4 lectin-labelled cells were also OX 42 immunoreactive, but co-existence of OX-42 immunoreactivity and NADPH diaphorase reactivity was not observed. Only a small minority of NADPH-diaphorase reactive cells did not exhibit I-B4 lectin binding. In contrast to the simple somatic morphology of the majority of NADPH-diaphorase-reactive cells, the I-B4 lectin-negative cells had a ramified appearance, and while readily observed at two days postlesion, they were only rarely seen at three days postlesion. Primary cultures of bovine aortic endothelial cells also exhibited NADPH-diaphorase reactivity which occupied most of the cytoplasm in a filamentous web pattern. Endothelial cells possess a constitutive form of nitric oxide synthase which, as demonstrated in NADPH-diaphorase-reactive neurons, may be the basis of their NADPH-diaphorase reactivity. These findings indicate that NADPH-diaphorase reactive cells observed at lesion sites are probably angiogenic endothelial cells not associated with extant blood vessels. Thus, NADPH-diaphorase histochemistry offers an effective method of visualizing neovascularization in the brain and other tissues. PMID- 8487947 TI - Long-term protective effects of human recombinant nerve growth factor and monosialoganglioside GM1 treatment on primate nucleus basalis cholinergic neurons after neocortical infarction. AB - Neocortical infarction induces biochemical and morphological retrograde degenerative changes in cholinergic neurons of the rat nucleus basalis magnocellularis [Sofroniew et al. (1983) Brain Res. 289, 370-374]. In the present study, this lesion model has been reproduced in the non-human primate (Cercopithecus aethiops) to investigate whether degenerative changes affecting the cortex surrounding the lesioned area and the ipsilateral basal forebrain are prevented by the early administration of recombinant human nerve growth factor alone or in combination with the monosialoganglioside GM1. Six months after surgery and treatment, the monkeys were processed either for biochemistry (choline acetyltransferase assay) or immunocytochemistry. In lesioned vehicle treated animals, choline acetyltransferase activity significantly decreased by 28% in the cortex surrounding the injured area and by 31% in the ipsilateral nucleus basalis of Meynert when compared with values of sham-operated monkeys. These biochemical changes were fully prevented with the administration of nerve growth factor alone or in combination with the monosialoganglioside GM1. The morphometrical analysis revealed a significant shrinkage of cholinergic neurons (61 +/- 1.4% of sham-operated cell size) and loss of neuritic processes (59 +/- 10% of sham-operated values) within the intermediate nucleus basalis region of lesioned vehicle-treated animals. Although a protection of the cholinergic cell bodies within the nucleus basalis was found with both treatments, a significant recovery of the neuritic processes (84 +/- 7.2% of sham-operated values) was assessed only in the double-treated monkeys. These results indicate that the early administration of nerve growth factor alone or in combination with the monosialoganglioside GM1 induces a long-term protective effect on the nucleus basalis cholinergic neurons in cortical injured non-human primates. PMID- 8487948 TI - Cholecystokinin-dependent regulation of host dopamine inputs to striatal grafts. AB - Intrastriatal infusions of cholecystokinin-8-sulphate in the rat exerts a dose dependent inhibition of dopamine-release from nigrostriatal terminals in the neostriatum, as measured by push-pull perfusion. This effect is abolished by excitotoxic lesions of the neostriatum, which, along with behavioural, electrophysiological and receptor binding studies, suggests that cholecystokinin exerts its action indirectly on dopamine release via receptors located on intrinsic striatal neurons. Grafts of embryonic striatum implanted in the lesioned striatum become innervated by host-derived dopamine axons and restore the response of those host neurons to cholecystokinin infusion. This suggests that the innervation of the grafts by dopaminergic axons of the host brain does not simply provide a tonic input to the grafts, but rather represents a phasic input that is under dynamic local regulation by graft-host feedback influences from the transplanted neurons themselves. PMID- 8487949 TI - Dopamine decreases striatal enkephalin turnover and proenkephalin messenger RNA abundance via D2 receptor activation in primary striatal cell cultures. AB - Dopaminergic regulation of striatal enkephalin biosynthesis and secretion was studied in primary neuronal cultures from fetal rat striatum. To allow pharmacological treatment, striatal primary cell cultures were seeded in chemically defined medium onto extracellular matrix. In these conditions, pharmacological treatment of the striatal neurons on the 10th day in vitro for 48 h with 10(-6) M dopamine induced a 50% decrease in preproenkephalin mRNA level concomitant with a 50% decrease in methionine enkephalin neuronal content. These effects of dopamine were mimicked by the D2 agonist bromocriptine (10(-6) M). The decrease in methionine enkephalin neuronal content induced by dopamine or bromocriptine was reversed by the simultaneous application of sulpiride (10(-6) M), a selective D2 antagonist. Interestingly, the D1 agonist SKF 38393 (10(-6) M) application for 24 or 48 h was found to have no significant effect on methionine enkephalin neuronal content. To ensure dopamine regulation of enkephalin secretion, shorter dopaminergic treatments were performed. Dopamine application (10(-6) M) for 2 h had no significant effect on basal methionine enkephalin secretion but significantly decreased (50%) methionine enkephalin secretion induced by KCl 56 mM. This effect of dopamine on the KCl-induced methionine enkephalin secretion was mimicked by bromocriptine (10(-6) M), reversed by sulpiride (10(-6) M) and unaffected by the D1 antagonist SCH 23390 (10(-6) M) application onto striatal neurons. Our data provide direct evidence for a dopaminergic inhibitory control on enkephalin biosynthesis and secretion from striatal cell cultures, mediated through the dopaminergic D2 receptor activation. PMID- 8487950 TI - Organotypic slice cultures of the rat striatum--I. A histochemical and immunocytochemical study of acetylcholinesterase, choline acetyltransferase, glutamate decarboxylase and GABA. AB - Slices of striatal tissue from newborn to eight-day-old rats were cultured for six to 47 days. Cholinergic neurons and fibres were then visualized by histochemical staining for acetylcholinesterase or immunocytochemical staining for choline acetyltransferase. GABA-containing neurons and fibres were visualized by immunocytochemical staining for glutamate decarboxylase or GABA. Corresponding to the normal postnatal development in vivo, acetylcholinesterase staining of the striatal tissue progressed from a "patchy" distribution in the six to 14 days old cultures to an almost even distribution of high acetylcholinesterase activity after 18-27 days. Extrinsic afferents were accordingly not necessary for the maintenance of a patch-matrix-like, acetylcholinesterase distribution during the first one to two weeks in culture, just as a subsequent, normal developmental change of the acetylcholinesterase staining pattern into a more homogeneous distribution also occurred without such afferents. Cholinergic, choline acetyltransferase-immunoreactive neurons were evenly distributed within the cultured striatal tissue, like in vivo, but the density of the neurons appeared to be higher in the cultures. The neurons had a morphology corresponding to the "classical", large-sized, aspiny, cholinergic interneurons in the adult rat striatum. Glutamate decarboxylase-immunoreactive and GABA-immunoreactive neurons were either lightly or darkly stained and of medium size, but some large, lightly stained glutamate decarboxylase-immunoreactive and GABA-immunoreactive neurons were also found. The difference in staining density among the medium-sized cells was observed with both antisera and hence provide evidence for the existence of two populations of medium-sized GABAergic neurons, which in vivo are intensely stained interneurons and more weakly stained, spiny projection neurons. Fibres stained better for glutamate decarboxylase than for GABA and outgrowth of glutamate decarboxylase-immunoreactive nerve fibres from the striatal slice cultures onto the coverslip was often observed. The presence at all culture periods of "protospines" on cell bodies and proximal dendrites of some glutamate decarboxylase-immunoreactive, and in particular some GABA-immunoreactive neurons, suggested that at least some developmental characteristics might be maintained for extended periods in culture. In several cultures, groups of small GABA immunoreactive cells were observed. Similar groups were also found by staining for glutamate decarboxylase, but a smaller proportion of the cells were then positively stained. In view of their immature appearance with few or no processes, the known presence of GABA in neuroblast-like cells, and the recent demonstration of neuronal and glial progenitor cells in the adult mouse striatum, the small cells might belong to a population of undifferentiated cells surviving in the slice cultures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8487951 TI - Response of locus coeruleus neurons to footshock stimulation is mediated by neurons in the rostral ventral medulla. AB - While it is well documented that locus coeruleus neurons are potently activated by foot-pinch or sciatic nerve stimulation, little is known about the circuit producing this sensory response. Previous work in our laboratory has identified the medullary nucleus paragigantocellularis as a major excitatory afferent to the locus coeruleus. Here, we use local microinjections into the paragigantocellularis to test whether this nucleus is a link in the pathway mediating the activation of locus coeruleus neurons by subcutaneous footpad stimulation, or footshock, in anesthetized rats. Lidocaine HCl microinjected into the paragigantocellularis reversibly attenuated footshock-evoked activation of 50 out of 56 locus coeruleus cells, with responses in 20 cells completely blocked. Microinjections of GABA into the paragigantocellularis reduced the footshock evoked responses of 17 out of 27 locus coeruleus cells (seven complete blocks); microinjections of the GABAB agonist baclofen had no effect (0 out of 11 cells blocked). Microinjections of a synaptic decoupling cocktail of manganese and cadmium also attenuated locus coeruleus activation in eight out of nine cells with two complete blocks. With each agent, the most effective injection placement for complete blockade of responses was the ventromedial paragigantocellularis; injections bordering this region attenuated responses, while those outside of the paragigantocellularis (dorsal medullary reticular formation, nucleus tractus solitarius, or facial nucleus), or vehicle injections, were ineffective. These results are consistent with previous findings that pharmacologic blockade of paragigantocellularis-evoked locus coeruleus activity also blocks footshock evoked responses of locus coeruleus neurons [Ennis and Aston-Jones (1988) J. Neurosci. 8, 3644-3657], and support the view that this somatosensory response, and perhaps other sensory-evoked responses of locus coeruleus neurons, involve the nucleus paragigantocellularis. PMID- 8487952 TI - Expression of c-fos in restricted areas of the basal forebrain and brainstem following single or combined intraventricular infusions of vasopressin and corticotropin-releasing factor. AB - Vasopressin has been shown to be localized in specific central nervous system (CNS) sites. There is considerable evidence that it can act as a central neurotransmitter and it has been ascribed a variety of putative roles in the CNS. To identify those regions of the brain capable of responding to this peptide, 250 pmol vasopressin were infused into the lateral ventricle intracerebroventricular of conscious, handled male rats, and their brains processed for fos immunohistochemistry 60 min later. Increases in fos-immunoreactivity, compared with cerebrospinal fluid-infused controls, were found in specific regions of the basal forebrain and brainstem: the central nucleus of the amygdala, ventrolateral septum, parvocellular divisions of the paraventricular nucleus of the hypothalamus, dorsal tuberal nucleus and locus coeruleus. Pre-infusion of 2500 pmol of a V1a antagonist prevented or reduced the expression of c-fos by intracerebroventricular vasopressin in all areas except the dorsal parvocellular paraventricular nucleus, implying that in most (but not all) areas the actions of vasopressin are mediated by the V1a receptor. Central administration of vasopressin had no effect on plasma corticosterone levels. Vasopressin and corticotropin-releasing factor act synergistically on the anterior pituitary to cause release of adrenocorticotropic releasing hormone and have corresponding synergistic interactions on behaviour. Infusion of 250 pmol corticotropin releasing factor produced a similar but not identical pattern of fos-like immunoreactivity to that of vasopressin. Activation of the parabrachial nucleus was observed, but there was no significant effect on the lateral septum and apparent increases in the medial parvocellular division of the paraventricular nucleus and locus coeruleus were not significant. Corticotropin releasing factor also caused a marked rise in plasma corticosterone. When the two peptides were infused together (125 pmol each) no evidence for synergy was found, in terms of the number of neurons activated to express c-fos. The induction of differential patterns of fos-like immunoreactivity by vasopressin and corticotropin-releasing factor in specific regions of the limbic forebrain and brainstem has implications for the individual roles they play in the CNS. PMID- 8487954 TI - Regressive modifications of climbing fibres following Purkinje cell degeneration in the cerebellar cortex of the adult rat. AB - The role of postsynaptic neurons in the maintenance of adult terminal axon arbours was investigated in the rat olivocerebellar system. The degeneration of Purkinje cells, the main target of olivary axons in the cerebellar cortex, was obtained by intraparenchymal application of kainate. The structural features of target-deprived climbing fibres, visualized by Phaseolus vulgaris leucoagglutinin tracing, were examined from two days to six months after the lesion. Following the degeneration of its Purkinje cell, the climbing fibre underwent remarkable regressive modifications involving the disappearance of most of the terminal arborization. Never the less, atrophic arbours still spanned through the molecular layer six months after the lesion. Morphometric evaluations showed that, one week after kainate application, total arbour length was already reduced to 52% of control, whereas the number of branches and of varicosities had both dropped around 40%. This retraction process progressed in the following stages to reach its maximum at about one month after the lesion, when total length was 30% of control and only 10% of branches and varicosities were still present. Only a slight tendency to a further decrease of the values could be detected at longer survival times. Branching pattern analysis revealed that such regressive phenomena mainly involved the distal compartment of the climbing fibres, the one made of fine varicose branchlets, while sparing the proximal thick branches. In addition, the whole process appeared to follow some rather strict guiding principles leading to an ordered branch retraction, from the periphery of the arbour inwards. Finally, in order to rule out the possibility that the observed changes could be due to a direct action of kainate on climbing fibres, we designed an alternative method of killing Purkinje cells by intraparenchymal injection of propidium iodide. The structural features of climbing fibres deprived of their target by such a procedure were very similar to those shown by arbours from time-matched kainate-lesioned animals at both qualitative and quantitative levels. Our results show that target deprivation induces remarkable structural modifications in the climbing fibre, leading to the retraction of most of the arbour. Never the less, the integrity of the Purkinje cell is not necessary for the maintenance of the whole arborization since its proximal compartment is maintained in the molecular layer for several months after target degeneration. It is proposed that the Purkinje cell, most likely by acting through a contact factor, directly controls the formation and the maintenance of the distal climbing fibre branches with their varicosities, which represent the presynaptic compartment of the axonal arbour. PMID- 8487953 TI - Induction and suppression of immediate early genes in specific rat brain regions by the non-competitive N-methyl-D-aspartate receptor antagonist MK-801. AB - The expression pattern of six different immediate early gene-encoded proteins was examined in the rat forebrain after intraperitoneal administration of MK-801, a non-competitive N-methyl-D-aspartate receptor antagonist, at doses of 3 mg/kg and 0.3 mg/kg, respectively. Following MK-801 treatment, the presence of c-FOS, FOS B, KROX-24, c-JUN, JUN B, and JUN D were investigated by immunocytochemistry with specific antisera at different time intervals up to 48 h. Selective induction of all six immediate early genes was found in layer III neurons of the posterior cingulate and retrosplenial cortex. More complex effects were observed in the neocortex: MK-801 did not influence constitutive expression of different FOS and JUN proteins, but caused marked induction of c-FOS, FOS B, JUN B and JUN D, mainly in layer IV, but also in layers V and VI. In contrast, strong neocortical constitutive expression of KROX-24 was almost abolished by MK-801 administration, and replaced by an expression pattern similar to that of FOS and JUN proteins. Subcortical areas such as the hypothalamus and thalamus demonstrated an induction of a subset of immediate early genes (c-fos, fos B, Krox-24, jun B). Injection of MK-801 caused the same distributional pattern of immediate early gene expression irrespective of the dose given, but the extent of changes was stronger after 3 mg/kg, and altered levels of immunoreactivity persisted longer. In many experimental paradigms, immediate early genes are induced by N-methyl-D-aspartate receptor-mediated mechanisms. This induction can readily be blocked by N-methyl-D aspartate receptor antagonists like MK-801. Our data, however, indicate that MK 801 itself causes immediate early gene expression in specific neuronal populations. In the present study MK-801-elicited expression of immediate early gene-encoded proteins seems to identify reversibly injured neurons, mainly in layer III of the posterior cingulate and retrosplenial cortex. These neurons have previously been shown to be the principal target of N-methyl-D-aspartate receptor antagonist toxicity. Since immediate early gene induction precedes heat-shock protein expression as well as pathomorphological changes, and is induced in additional cortical cell populations, it seems to be a more rapid and more sensitive indicator of non-lethal neuronal injury. PMID- 8487955 TI - Physiological influence of lateral proisocortex on the midbrain periaqueductal gray: evidence for a role of an excitatory amino acid in synaptic activation. AB - Recent anatomical studies in this laboratory have demonstrated that the proisocortex cortex adjacent and dorsal to the rhinal sulcus is one of the major forebrain afferent inputs to the midbrain periaqueductal gray matter in the rat. The physiological influence(s) of this projection has not been examined. The present studies investigated the responses of periaqueductal gray neurons to chemical and electrical stimulation of proisocortex in chloral hydrate anesthetized rats. In addition, the role of glutamate as a possible transmitter in excitatory proisocortex-periaqueductal gray synaptic responses was tested. Microinjection of D,L-homocysteate into proisocortex excited 44% (19/43), inhibited 37% (16/43) and had no effect on 19% of periaqueductal gray cells. The onset of D,L-homocystic acid-evoked responses ranged from 2 to 60 s; the duration of responses ranged from 1 to 18 min. Low-frequency, single-pulse electrical stimulation of proisocortex robustly altered neuronal discharge in 25% of periaqueductal gray neurons sampled; 10% (74/724) of neurons were excited and 15% (107/724) were inhibited. Insular cortex-evoked excitatory responses had a mean onset latency of 19.5 +/- 4.2 ms and a mean duration of 38.5 +/- 26.9 ms. Inhibitory responses had a mean onset latency of 26.2 +/- 15.6 ms and mean duration of 108.0 +/- 84.9 ms. Trains of high-frequency electrical stimulation of proisocortex excited 22% (13/59) and inhibited 25% (15/59) of periaqueductal gray cells tested. In separate experiments, stimulation electrodes were placed in periaqueductal gray to antidromically activate proisocortex neurons that project to periaqueductal gray.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8487957 TI - Identification of a novel neuron-specific surface antigen in the developing nervous system, by monoclonal antibody 4C5. AB - Monoclonal antibody 4C5 was obtained after immunization of Balb/c mice with a crude membrane preparation derived from the brains of 15-day-old rat embryos. As revealed by immunocytochemistry on primary cell cultures from embryonic rat brain, it was shown that the antigen recognized by monoclonal antibody 4C5 (4C5 antigen) is localized on the cell surface of the neurons. Preliminary biochemical characterization showed that it is a peripheral protein with a molecular weight of 94,000. The 4C5 antigen does not appear to be linked with other polypeptides by S--S bonds and contains few or no disulphide intramolecular bridges. N Glycanase digestion indicated that the protein is probably not glycosylated. Monoclonal antibody 4C5 crossreacts with membrane fractions from rat, rabbit, pig and human developing brain. It was shown by immunohistochemistry that the 4C5 antigen is widely distributed in the embryonic and adult rat brain. In the peripheral nervous system 4C5 immunoreactivity was present in dorsal root ganglion neurons. Immunoblotting and immunohistochemistry on dissociated cells from rat brain and on tissue sections of brain and dorsal root ganglia revealed an age-dependent decline in the expression of the epitope recognized by monoclonal antibody 4C5, in the central and peripheral nervous system. In particular, intense 4C5 immunoreactivity was observed during the embryonic and early postnatal ages. By the second postnatal week, expression of the protein was greatly reduced, becoming very weak at later stages of development and in the adult animal. In PC12 cell cultures, expression of the 4C5 antigen was intense in proliferating cells while being greatly reduced after nerve growth factor induced differentiation of these cells. The increased expression of the 4C5 antigen in proliferating PC12 cells and the prominent presence of this molecule during a time of neuronal migration suggest that it is involved in these developmental events. PMID- 8487956 TI - Expression patterns of the cell adhesion molecule Nr-CAM during histogenesis of the chick nervous system. AB - Neuron-glia-related cell adhesion molecule (Nr-CAM) is a recently characterized cell adhesion molecule in the family of immunoglobulin-related molecules of which the neural cell adhesion molecule, N-CAM, is the prototype. Nr-CAM shares structural properties with another member of this family (neuron-glia CAM, Ng CAM) and both molecules exhibit homophilic and heterophilic binding properties. To understand better the role of such molecules in development, we have examined the sites of synthesis and expression of Nr-CAM by means of in situ hybridization and immunohistochemistry. Both methods indicated that Nr-CAM is expressed only in the nervous system. The molecule was observed on neurons in both the peripheral and central nervous systems and on epithelial floor plate cells in the spinal cord, but it was absent in the germinal zones. The protein was present on perikarya, but was found preferentially on axonal tracts. As observed for messenger RNAs specifying other cell adhesion molecules, messenger RNA for Nr-CAM was localized in the perikarya. The temporal expression of Nr-CAM was correlated with various neural morphoregulatory events, including cell proliferation and migration, axonal outgrowth and myelination. The molecule was expressed during the onset of neurogenesis at embryonic day 3 in the floor plate epithelium, and then on postmitotic ventral horn motor neurons of the spinal cord. At later stages, it was expressed throughout the spinal cord but disappeared from the floor plate. In the cerebellum, Nr-CAM was found on granule and Purkinje neurons and afferent fibers. Both local and projection neurons in the optic tectum, as well as axonal pathways throughout the telencephalon, expressed Nr-CAM. In the peripheral nervous system, Nr-CAM was expressed strongly in sensory and autonomic ganglia and in the enteric nervous system. At the onset of myelination, there was a general decrease in staining for Nr-CAM protein in the central nervous system but not in the periphery. Comparison of the expression of Nr-CAM to that of the structurally related Ng-CAM showed considerable overlap in their distributions, although there were differences in the levels at which each CAM was observed in particular structures. For example, sympathetic ganglia stained more intensely for Nr-CAM protein than for Ng-CAM. This differential but co-distributed pattern is consistent with the idea that although similar cell adhesion molecules have independent binding specificities, they may have related functions that act synergistically in the development of the nervous system. PMID- 8487958 TI - The effects of chlormethiazole and nimodipine on cortical infarct area after focal cerebral ischaemia in the rat. AB - Focal ischaemia in the rat cerebral cortex was produced by means of a photochemically induced thrombosis of cerebral arteries. This was achieved by intravenous infusion of the photosensitive dye Rose Bengal and illumination of the skull with focused green light. Initial experiments justified the use of tetrazolium staining as an index of infarct damage. Using this technique it was demonstrated that chlormethiazole (200 mg/kg, i.p.) given 5 min post ischaemia markedly reduced the area of infarcted cortical tissue. A second experiment replicated this observation and showed that, in contrast, nimodipine (0.5 mg/kg, i.p.) given 5 min post infarct was without effect on infarct size. The pattern of Evans Blue extravasation indicated that the infarct developed over a 24-h period with the major damage occurring in the first 4.5 h. The spread of the infarct beyond the initial core of damage was decreased by an estimated value of almost 50% by injection of chlormethiazole (200 mg/kg, i.p.) 5 min after the light exposure. These data indicate that chlormethiazole is an effective drug in protecting against the effects of focal ischaemia in the rat and, taken with earlier observations that chlormethiazole protects against the effects of global ischaemia in the gerbil, suggest that the drug may be an effective treatment against the ischaemic cell death that can occur following a stroke or cardiac arrest. PMID- 8487959 TI - Hypothalamic melanin-concentrating hormone and alpha-neoendorphin-immunoreactive neurons project to the medial part of the rat parabrachial area. AB - Neurons in the middle and posterior parts of the lateral hypothalamus project to the parabrachial area, and in particular to the gustatory relay-station located in the medial part of this area. In the present study we have examined some of the neuropeptide immunoreactivities of the lateral hypothalamus neurons that project to the gustatory region of the parabrachial area. By coupling retrograde transport and immunohistochemistry, we found that 50-60% of medial parabrachial area-projecting cells located in the juxta-capsular region of the posterior lateral hypothalamus are labeled by rat melanin-concentrating hormone antiserum, while 28% of the retrogradely labeled neurons located in the perifornical lateral hypothalamus are visualized with alpha-neoendorphin antiserum. Moreover, a large number of terminals distributed throughout the parabrachial nucleus are immunoreactive to melanin-concentrating hormone or alpha-neoendorphin antisera. These immunoreactivities are not co-localized within the same lateral hypothalamic neurons. The potential role of these peptidergic projections in the reward mechanisms elicited in the medial parabrachial area and in the control of palatability is discussed. PMID- 8487960 TI - Gulf War veterans with PTSD. PMID- 8487961 TI - Evaluation of gender differences in urine specific gravity and serum electrolytes in response to varied fluid intake and ibuprofen use. AB - Heat casualties and other conditions related to suboptimal fluid intake (FI) are common in the military. Current methods to assess FI do not address gender differences or medication use, specifically non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used in the field. Nine men and six women were prospectively studied while stationed in Saudi Arabia. Urine specific gravity and serum electrolytes were monitored as FI was varied before and after daily ibuprofen (IBP) ingestion. IBP impaired urinary dilution in both men and women, but differences were not statistically significant pre- and post-IBP or between genders. Use of IBP or other NSAIDs may confound usual methods to ensure adequate FI, and soldiers should be specifically questioned about their use before such assessments. PMID- 8487962 TI - Deployment of an Air Transportable Hospital in support of Allied Forces during Operation Provide Comfort: April 29 to July 17, 1991. AB - The deployment, setup, and operation of an Air Transportable Hospital (ATH) as a primary field hospital for 25,000 Allied Forces during Operation Provide Comfort is presented with a description of the performance and experiences of this unit. More than 3,300 outpatients were seen and treated, and more than 50 patients were operated on at the ATH. In addition, assigned personnel participated as medical augmentees to Kurdish refugees camps, screening and treating more than 13,000 individuals. The success of this deployment validates and expands the concept of the ATH and of Air Force training doctrine. PMID- 8487963 TI - A prophylactic program to prevent traveler's diarrhea in United States Naval personnel comparing doxycycline and trimethoprim-sulfamethoxazole. AB - A prophylactic program was designed to prevent traveler's diarrhea comparing the efficacy of doxycycline and trimethoprim-sulfamethoxazole. A total of 99 volunteers received either medication. No cases of traveler's diarrhea were reported in either group or in a control group not taking prophylactic antibiotics. The 42 volunteers taking doxycycline showed neither of its main two side effects, photosensitivity or gastrointestinal discomfort. Three of 57 volunteers taking trimethoprim-sulfamethoxazole had side affects from it--two with some gastric discomfort and one with a skin rash. Another common side effect, which did not occur, is diarrhea. This paper makes suggestions on managing a shipboard traveler's diarrhea prevention program and anticipating potential problems. PMID- 8487964 TI - Support systems at the U.S. government's only medical school, the Uniformed Services University of the Health Sciences. AB - A brief history and a discussion of general support management employed at the Uniformed Services University of the Health Sciences are given. This includes the "place" of support, leadership philosophy, and guiding principles. Guiding principles advocated by H. Edwards Deming were adopted. Some of the specific management techniques employed in instituting his 14-point plan are emphasized when making personnel selections, "immersing" them in the "culture," and maintaining the environment established. PMID- 8487965 TI - How psychiatric symptoms varied in World War I and II. AB - Psychiatric syndromes may be differentially expressed according to cultural expectation. An examination of the literature reveals a predominance of conversion symptoms in World War I and a relative decrease among World War II neuropsychiatric casualties. In the latter conflict, by contrast, "combat exhaustion" and psychosomatic disorders comprised the majority of non-psychotic psychiatric casualties. Determinants of this changing "vocabulary of distress" are discussed. PMID- 8487966 TI - A TQM involvement plan. AB - We present the plan used to change our 35-bed medical treatment facility to a Deming Total Quality Improvement environment. This was successfully intermeshed with the military hierarchical chain of command and has resulted in a paradigm shift in the least amount of time within the facility. We present this plan, its steps for implementation, and our Quality Council organization so that similar military medical units may learn from our experience. PMID- 8487967 TI - Impact of nutritional care upon return-to-duty rates. AB - Returning soldiers to duty is a primary goal of the medical department. One of the most critical factors in achieving this goal is the soldier's nutritional status--both prior to the trauma and during treatment. This article reviews the role of nutrition in healthy lifestyles, the effect of stress and the role of nutrition in wound healing, and the role of the registered dietitian in providing nutritional care. Implications for maximizing the return-to-duty rate through inclusion of a registered dietitian on the treatment team are identified. PMID- 8487968 TI - A major outbreak of foodborne gastroenteritis among Air Force personnel during Operation Desert Storm. AB - An outbreak of foodborne gastroenteritis affected 648 United States Air Force personnel stationed in Jeddah, Saudi Arabia during Operation Desert Storm. The implicated food source was a locally catered meal. Despite the presence of an aggressive Air Force public health program, foodborne illness had a major impact on manpower and medical resources during a critical phase of military operations. It is the recommendation of the authors that the Air Force not rely on local caterers during future deployments. PMID- 8487969 TI - Intraarticular autogenous bone grafting in recurrent shoulder dislocations. AB - In a reexamination, 24 young soldiers who had been operated on using a new method of screwing an autogenous bone graft into the glenoid rim in cases of recurrent dislocation of the shoulder joint were investigated. A major functional problem is the reduced lateral rotation, even by using other procedures for operative treatment like Eden-Hybinette or Putti-Platt. This reduction of shoulder movement results in problems using the affected arm during sporting activities or military duties. There has been an excellent result without any redislocation in a follow through of 6 to 42 months and more than 90% satisfied patients, with only a very low rate of reduction of lateral rotations about 10 degrees using this procedure. The X-rays of all the patients, reinvestigated, showed a complete healing of the bone grafts into the glenoid rim and correct position of AO-screws. PMID- 8487970 TI - An examination of narcissistic personality traits as seen in a military population. AB - Various studies examining the prevalence of personality disorders in civilian inpatient and outpatient populations have consistently found narcissistic personality disorder to be one of the least common. In striking contrast to this, a recently published study showed narcissistic personality features to be among the most common personality features in a military outpatient clinic population. This paper examines several possible explanations for this finding. This surprisingly high relative incidence of narcissistic personality features may be related to a self-selection bias on the part of persons choosing a military career. Narcissistic personality traits may confer adaptive advantage in certain military professional roles. Kohut's theory of specific transference requirements in individuals with narcissistic character structure serves as a useful explanatory model for these findings. PMID- 8487971 TI - A review of sternal wound complications in a military hospital. AB - A retrospective review of sternal wound complications was conducted during a recent 13-month period at the Naval Hospital, San Diego. These complications developed in 5 (3.0%) of 168 patients after they underwent coronary artery bypass with saphenous vein grafts. Three or more of these patients were male, obese, and hypertensive, with a significant smoking history. All these factors have been previously reported to be associated with an increase in the incidence of sternal wound complications. All patients had prolonged postoperative intensive care treatment, and ultimately all patients recovered and were discharged from the hospital. Interestingly, as opposed to other reviews, we were unable to show an association of sternal wound complications with the use of internal mammary artery harvesting. PMID- 8487972 TI - Physical fitness and cardiovascular disease risk factors of female senior U.S. military officers and federal employees. AB - This study compared physical fitness and cardiovascular risk factors between military officers (N = 23) and civilians (N = 17). Subjects were women (average age 43 years) who attended the U.S. Army War College from 1986-1991. Officers had less body fat, higher aerobic capacity, lower resting heart rates, lower resting diastolic blood pressure, higher HDL, and marginally lower triglycerides. Female military officers appear to be more fit and have lower cardiovascular risk factors than their civilian counterparts. PMID- 8487973 TI - The history of the military medical service in Poland. PMID- 8487974 TI - The clinical assessment of femoral stress fractures: a comparison of two methods. AB - In a prospective study among 667 recruits, the incidence of asymptomatic femoral stress fractures was compared using a new expanded stress fracture clinical examination (SFCA) versus an older stress fracture examination. There was a statistically significant difference (p = 0.0001) between the percentage of femoral stress fractures that were asymptomatic in the group evaluated by SFCA (26%) and those evaluated by the older stress fracture examination (80%). By using the SFCA, many of the femoral stress fractures previously classified as asymptomatic are in fact recognized as symptomatic. PMID- 8487975 TI - The use of computed tomography to assess and treat complex pneumothorax. AB - A complex pneumothorax is a loculated pneumothorax due to adhesions. Chest roentgenograms are usually inadequate to assess a complex pneumothorax. A computed tomography (CT) scan can be used to accurately assess the extent of the pneumothorax, and to determine its exact location in order to make placement of a tube thoracostomy easier and safer. In addition, if there is a persistent or recurrent pneumothorax after tube thoracostomy, a CT scan can be used to determine the relationship of the chest tube to the pneumothorax. Three cases are discussed to illustrate the use of the CT scan in evaluating patients who have a complex pneumothorax. PMID- 8487976 TI - Osteoradionecrosis of the temporal bone: treatment with hyperbaric oxygen therapy. AB - Radiation necrosis is a major complication of surgery or trauma in a previously irradiated field. Although it may occur in any location, the most common region affected is the head and neck. Osteoradionecrosis (ORN), the involvement of bone with radiation necrosis, occurs most frequently in the mandible, and has been well described. Involvement of the temporal bone, although less frequent, is nonetheless a difficult problem in management. Described herein is a case of ORN of the temporal bone treated with adjunctive hyperbaric oxygen therapy with complete resolution. This is followed by a discussion of the pathophysiology, presentation, and management of osteoradionecrosis of the temporal bone, including the role of adjunctive hyperbaric oxygen in the treatment regimen. PMID- 8487977 TI - A one-year experience in the antenatal evaluation of suspected abdominal wall and bowel defects at a military tertiary referral center. AB - A variety of fetal abdominal wall defects and bowel anomalies are detected or suspected antenatally at institutions providing primary, secondary, and tertiary level care. Presented is a summary of a 1-year experience at a tertiary care center demonstrating a working referral network and its advantages. Of the 10 cases presented, 8 were referred and 2 originated from within our institution. The initial diagnosis was uncertain or differed from the final diagnosis in half of referred cases. Within the military, a reliable route for referral enhances prenatal evaluation and provides intensive neonatal support at delivery if needed and more immediately available surgery if indicated. PMID- 8487978 TI - Promoting the use of program evaluation findings. AB - Although program evaluations promote organizational hygiene by early detection of problems, many faculty experience evaluation phobia. To overcome this phenomenon, the author discusses four major strategies for faculty and administrators. PMID- 8487979 TI - The multifocused faculty selection model: a design for hiring the best faculty. AB - The multifocused faculty selection model is designed to assist the faculty search committee in two ways. First, this model organizes the stages for obtaining information about the applicant's abilities related to faculty performance. Second, the model provides a consistent method for faculty selection as the membership of the department's search committee changes. The applicant selection techniques used in this model include descriptive interviewing, computer assisted data, and the teaching demonstration. PMID- 8487980 TI - Eliminating sexism in the classroom. AB - Sexism exists in many nursing classrooms without the teacher or students being aware of it. Speech patterns, written-communication, and pedagogical styles may contribute to sexism. Nurse educators need to take measures to identify and eliminate sexism from the classroom, because it subordinates and limits students. The classroom should promote gender-free situations that enhance and contribute to learning and advancement of all students. PMID- 8487981 TI - Have program, will travel! AB - A lack of nurses with masters degree preparation on Guam resulted in a contract with Washington State University to deliver its graduate program to Guam. Faculty who taught the first of four consecutive summer sessions identified many issues in transporting themselves and a total program 6,000 miles away from the home campus. The authors provide suggestions for dealing with administrative, curricular, faculty, and student concerns that may help others plan international education endeavors. PMID- 8487982 TI - Transformation: nursing education and cultural diversity. AB - Teaching is the transformation of ideas and content into representations that are appropriate for particular students. The teacher moves from a personal understanding of an idea to its being comprehended by the students. Teachers change knowing into telling, and students change that telling into doing and caring. PMID- 8487983 TI - The use of group process in developing articulation models. AB - This article explores the use of group process for developing articulation models to enable movement of graduates between levels of nursing education with minimal barriers and repetition of content. Potential roadblocks to success include differing philosophical positions, lack of recognition of core content and end competencies of the different levels, and time commitments required. However, with careful planning and flexibility, group dynamics can be used proactively to achieve success. PMID- 8487984 TI - Learning style as a predictor of drug dosage calculation ability. AB - This study measured the learning style in mathematics of nursing students to determine if there was a correlation with their ability to calculate drug dosages. The results seem to indicate that instructors can improve the ability of their students to calculate drug dosages by integrating instructional methods that 1) reinforce the student's preferred learning style; and 2) require the student to use both sequential, step-by-step, paper and pencil processing and global, all-at-once mental processing. PMID- 8487985 TI - Reducing the sea of paper in nursing education. PMID- 8487986 TI - Assessing the effectiveness of oral presentations. PMID- 8487987 TI - The confidence scale: development and psychometric characteristics. AB - Developing confidence is an important component of clinical nursing practice, yet nurse educators do not have a valid and reliable instrument to measure confidence for tracking the development of this phenomenon or studying the factors that influence the level of confidence. The author discusses the C-Scale as a valid and reliable instrument to measure confidence. PMID- 8487988 TI - Your nursing image--tending the flame. PMID- 8487989 TI - Finding the magic words. PMID- 8487990 TI - Chloral hydrate overdoses implicated in deaths. PMID- 8487991 TI - Evaluating serum triglyceride levels. PMID- 8487992 TI - Pediatric near drowning. PMID- 8487993 TI - Jenni, RN. PMID- 8487994 TI - Critical incidents: pulling together to cope with the stress. PMID- 8487996 TI - Using blood glucose meters--what you and your patient need to know. Part III. PMID- 8487995 TI - T.B. the second time around ... and how you can help to control it. PMID- 8487997 TI - Predicting future trends in oncology nursing. PMID- 8487998 TI - New drugs. PMID- 8487999 TI - Nurses' guide to good nutrition and sensible weight control. Part 1. PMID- 8488000 TI - Weight loss programs. Is one right for you? PMID- 8488001 TI - Remembering Rose. PMID- 8488002 TI - Managing delirious patients. PMID- 8488003 TI - Exposure to H.I.V.--common sense precautions. PMID- 8488004 TI - [Studying at Sherbrooke. An experience of hope]. PMID- 8488005 TI - [Pregnant, we latch on to life]. PMID- 8488006 TI - [Liaison nurses in demand]. PMID- 8488007 TI - [Open window on the department of community health]. PMID- 8488008 TI - The emergence of new professional dynamics. PMID- 8488009 TI - [Alternative mechanisms of the "2(k) rule" for cellularity]. PMID- 8488010 TI - [The embryonic brain-derived neuralizing factor (EBDNF): its partial purification by ion-exchange and affinity chromatography]. AB - The data are presented about isolation from the brain of 7.5-day chick embryos of a factor capable of neuralizing effect on the early gastrula ectoderm of the grass frog Rana temporaria L. Earlier this factor was defined as embryonic brain derived neuralizing factor (EBDNF) (Mikhailov, Gorgoliuk, 1989). The isolation procedure includes (1) extraction with deionized water at pH 9.0; (2) ion exchange chromatography on a column with DEAE-adsorbent at pII 8.0; (3) affinity chromatography on Heparin-Ultragel column. EBDNF-containing fraction is eluted from the Heparin-Ultragel column with 250 mM NaCl as a separate peak. Four bands are observed on SDS-electrophoregrams of this fraction, two more prominent ones having the molecular weight of 43 and 63 kDa. The yield of EBDNF-containing fraction is about 0.01-0.02% of the wet weight of the initial brain tissue. PMID- 8488011 TI - [The tissue localization of "chitinoprotein", detectable by using specific antibodies, in the development of Drosophila melanogaster]. AB - The biosynthesis of cognate glycoproteins with chitinase-sensitive carbohydrate moiety ("chitinoproteins") was detected after incubation of cultured cells of different insect species with 3H-glucosamine (Kramerov et al., Insect Biochem. v. 20; 769-775, 1990). It was also demonstrated that production of the specific chitinoprotein takes place during the development of D. melanogaster as revealed by immunoblotting and autoradiographic analysis of crude tissue extracts. An investigation of the developmental pattern of tissue localization of Drosophila chitinoprotein was performed using antibodies raised in rabbit after immunization with a purified preparation of the chitinoprotein (ChiP) from Drosophila embryonic cultured cells. The paraffin-embedded thin (5 microns) sections of organisms fixed in Bouin fixative were stained immunohistochemically with primary antibodies and peroxidase-conjugated secondary antibodies followed by enhancement of the precipitated DAB product with osmium tetroxide. Preimmune serum and antiserum preadsorbed with the purified ChiP preparation were used as negative controls yielding no specific staining of tissue sections. Negative staining with specific anti-ChiP antibodies was demonstrated for salivary glands, gut, muscles, central and peripheral nerve system and some other tissues. A complex pattern of tissue-specific ChiP localization in a variety of tissues of ectodermal, mesodermal and germ line origin was revealed. The mesodermal derivatives- hemocytes and oenocytes capable of producing the components of cuticle as well as epidermal cells of larvae and imago clearly demonstrated staining of cytoplasmic vesicles, which in the latter case were exocytosed and included into the newly formed endocuticle. Another cell type known to produce cuticle--epithelial cells of imaginal discs (primordia of adult organs)--were also stained with antibodies. One can suppose that ChiP is involved in biogenesis of insect cuticle, probably, as a protein precursor of chitin formation. It was quite surprising to observe a rather strong staining of fat body cells and follicle cells of adult ovaries. The follicular epithelium secreted the stained granules into a growing oocyte that accumulated large amounts of this immunopositive material until transformation into a mature egg. In an early embryo ChiP is localized in blastodermal and pole cells, but not in yolk. This is, probably, the result of segregation of ChiP to the periphery of an egg during the final stage of its maturation and subsequent cellularization in the beginning of embryogenesis. Later ChiP can be found in ectodermal cells and hemocyte-like cells. It should be noted that not all amounts of ChiP detected in embryos are maternally inherited, for an active ChiP biosynthesis takes place in dissociated embryonic cells after incubation with labelled sugar precursor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488012 TI - [Melanotropic activity in the hypophysis and blood of Wistar rats in early postnatal development]. AB - The activity of melanotropins in pituitary homogenates and blood of Wistar rats obtained from the nursery Stolbovaia (Russian Academy of Medical Sciences) was studied using the method of biological testing (Hogben, Slome, 1931; Golichenkov, 1980). In order to elucidate, to what extent the normal status of melanotropic activity is retained in albino rats, two experimental series were performed. Melanotropic activity was determined in (1) intact rats and (2) in rats receiving subcutaneous injections of parachlorophenylalanine, a specific inhibitor of serotonin synthesis. Melanotropic activity of Wistar rats hypophysis during the studied period of development was similar to that of normal pigmented rats. However, the peak of melanotropic activity of blood which is characteristically observed in pigmented rats on day 3 of postnatal development is absent in the case of Wistar rats. The experimentally induced decrease in the serotonin level did not result in the increased melanotropic activity of blood. These data suggest that certain structures of hypophysis responsible for MSH secretion can be disturbed in Wistar rats. A short-term peak of blood MSH in rats during the first week after birth is known to provide for maturation of dopaminergic neurons located in the arcuate nucleus of the hypothalamus. Consequently, the absence of such peak in Wistar rats should result in neuroendocrine disturbances such as inadequate functioning of dopaminergic neurons responsible for melanotropin secretion by hypophysis beginning from the second week after birth (Lichtensteiger, Schlumpf, 1986). PMID- 8488013 TI - [The effect of methylazoxymethanol on neuronal differentiation in the murine cerebellum]. AB - The effect of methylazoxymethanol (MAM), an antimitotic drug, on granule and Purkinje cells of the rat cerebellum was studied. MAM was injected subcutaneously into ICR mice on day 5 after birth. The number of nucleoli and DNA content in nuclei of cerebellar neurons were determined 2 and 12 days after the injection. The number of nucleoli served as a criterion of maturity of neurons. On day 2 after MAM administration the proportion of Purkinje cells containing a smaller number of nucleoli increased suggesting a direct effect of MAM on maturation of Purkinje neurons. On day 12 no difference in the number of nucleoli was found between experimental and control animals but the number of granule cells containing multiple nucleoli increased significantly. The latter suggests that the studied cell population was supplemented with less mature cells. As a result, development of Purkinje and granule cells is desynchronized and that appears to determine the secondary effect of MAM on Purkinje cell differentiation. PMID- 8488014 TI - [An androgenic program of expression of the particular estrogen-binding protein is present in male rats in all hepatocytes]. AB - Radioligand and immunohistochemical analysis was used for studying the expression of an unusual estrogen-binding protein (UEBP) in the regenerated liver of male rats poisoned with CCl4. As a result of CCl4 poisoning, most hepatocytes intensely producing UEBP and located in the central part of the liver lobules are destroyed (40 to 90% of the liver parenchymal cells). Dead cells are substituted by new hepatocytes formed due to proliferation of periportal hepatocytes in which UEBP is expressed at a low level. In regenerated liver, however, a high level of UEBP expression characteristic of the control animals is restored, as well as a gradient mode of distribution of UEBP-containing cells with the maximum UEBP concentration in hepatocytes surrounding the central vein. The results obtained with animals with either intact or removed testes were similar, except that the dynamics of liver regeneration was slower in the castrated rats. These data suggest the existence in all hepatocytes of the complete androgen-related program for UEBP expression. This program is inherited by daughter cells in the absence of an inducing hormone and is similar in all cells, independently of the extent of its phenotypic expression in hepatocytes with different localization within the liver lobule. PMID- 8488015 TI - [The formation of T-suppressors that suppress the activity of alloreactive T cells after lymphocyte interaction with 2 different thymus-derived mediators]. AB - The data are presented on simultaneous interaction of thymocytes and T-cells from lymph nodes with two humoral factors produced by macrophages and epithelial cells, main stromal elements of the thymus. Such contact of T-cells with two mediators resulted in the formation of T-suppressors capable of inhibiting the activity of syngeneic allospecific T-lymphocytes. These T-suppressors did not alter the response to another antigen but inhibited proliferation of donor cells. Involvement of such mechanism of T-suppressor formation in regulation of the immune status is discussed. PMID- 8488016 TI - [Phenogenetic analysis of independent and dependent differentiation]. PMID- 8488017 TI - Thrombolytic therapy for acute myocardial infarction after oral surgery. AB - Two cases of mild-to-moderate bleeding after thrombolytic streptokinase therapy are presented, and the treatment modalities are discussed. To the best of our knowledge, these are the first two cases reported in the medical and dental literature. PMID- 8488018 TI - A simple method to enable feeding during maxillomandibular fixation of the jaws. AB - The use of maxillomandibular fixation after surgery on the jaw bone invariably affects the dietary intake and the oral hygiene of patients. When the upper and lower jaws are kept in occlusion, the patient has to take bland food that has to sieve through the crevices between teeth to enter the oral cavity. This results in food accumulation around teeth, orthodontic appliances, and surgical wound. Feeding in this manner can also be very trying on some patients. A simple method is devised in which finely minced food can be introduced by a catheter directly into the oral cavity. PMID- 8488019 TI - Third molars confusing the diagnosis of carcinoma. AB - The purpose of this study was to describe cases of oral cancer in which the initial presenting symptoms were considered to be due to third molars and in which the underlying carcinoma therefore escaped early diagnosis. Between 1986 and 1990 a total of five cases with squamous cell carcinoma associated with a third molar (impacted, partially or totally erupted, or recently extracted) were treated at our unit. Because of acute or chronic symptoms related to disturbed eruption of third molars, the detection of a simultaneous malignant change and referral were delayed. In conclusion, all third molars, especially impacted, partially erupted, or overerupted ones, should be examined critically, especially if the patient has symptoms. PMID- 8488020 TI - Dermoid cyst of the floor of the mouth. AB - Sublingual dermoid cysts are uncommon in the head and neck region. They are most often seen in young adults and can become unusually large with few symptoms. A case is presented to demonstrate the slow, expansive growth pattern and relatively painless swelling in the floor of the mouth that occurred over a 9 year period. PMID- 8488021 TI - Osteochondroma of the coronoid process of the mandible. Report of a case and review of the literature. AB - A review of the literature and the addition of one case have revealed that, on the basis of strict histologic criteria, there are presently 30 published cases of osteochondroma of the coronoid process of the mandible. Twenty-one cases (70%) were men. Most osteochondromas developed before the age of 40 years. The lesions were mushroomlike in more than two thirds of the cases. Deformity of surrounding structures and facial deformity was found in most cases. The surgical approach was intraoral in the majority of cases. None of the reported cases showed a recurrence. PMID- 8488022 TI - Central hemangioma of the mandible. AB - Central hemangioma of the mandible is a relatively rare condition; when it occurs, the clinical and radiographic presentation are often nonspecific. A proper diagnosis can be made with a high level of clinical suspicion, and imaging studies such as angiography can confirm the suspicion that a vascular lesion exists and can contribute valuable information to the preoperative data base. We report three cases of central hemangioma of the mandible demonstrating the variability of signs and symptoms and review the various treatment alternatives in the literature. We suggest that the treatment of choice for this entity is surgery, including reconstruction as necessary. PMID- 8488023 TI - McCune-Albright syndrome. Report of a case. AB - The McCune Albright syndrome is seldom encountered and rarely reported in dental literature. It represents a special category of polyostic fibrous displasia associated with skin pigmentation and endocrine disturbances. We describe the case of a 9-year-old boy with the McCune Albright syndrome, who was treated for a mandibular osteolytic lesion. PMID- 8488024 TI - Lobular adenocarcinoma of breast metastatic to the mandibular condyle. Report of a case and review of the literature. AB - A case of metastatic breast adenocarcinoma to the condyle in a 55-year-old white woman is reported. Highlights of this case presentation include the rarity of reported metastatic lesions to the condyle, a negative bone scan 2 months before the bone biopsy, the existence of a pathologic fracture as the only persistent symptom of the lesion, initial symptoms suggestive of temporomandibular joint disorder, and the uncommon type of breast carcinoma. PMID- 8488025 TI - A case of acromegaly identified after patient complaint of apertognathia. AB - Acromegaly results from the over production of growth hormone after the age at which the epiphyses of the bones have fused. The most common cause is an adenoma of the anterior pituitary gland. Early signs and symptoms are subtle and delayed diagnosis is common. The health consequences of untreated acromegaly are considerable. A brief description of the condition is given and a case report is included. The condition of the patient was first diagnosed after a dental examination at which he voiced a complaint of the inability to incise and a progressive open bite that he attributed to prosthetic treatment. On the basis of his intraoral radiograph history, it is probable that he developed the disease more than 5 years before its diagnosis. PMID- 8488026 TI - Perineural spread of squamous cell carcinoma involving trigeminal and facial nerves. AB - Perineural spread of squamous cell carcinomas in the orofacial region predominantly involves the trigeminal and facial nerves. Central spread, particularly along the trigeminal nerve, produces sensory impairment and involvement of other divisions through invasion of the gasserian ganglion, as illustrated in these case reports. Early diagnosis and medical referral is important because central invasion has a poor prognosis. PMID- 8488027 TI - Verruciform xanthoma in a bone marrow transplant recipient. AB - The verruciform xanthoma is an uncommon benign condition of uncertain cause that affects either mucosa or, less commonly, skin. Most lesions are solitary, and most have been reported to involve the oral mucosa. In some instances, chronic damage to the lesional site has been identified. This report describes a verruciform xanthoma that developed on the lower vermillion zone of the lip of a young person who had undergone allogeneic bone marrow transplantation for acute lymphoblastic leukemia. To our knowledge, this is the first reported case of this lesion occurring in a bone marrow transplantation patient. We speculate that immunologically mediated damage to the patient's epithelium in this area may be related to the pathogenesis of the lesion. PMID- 8488028 TI - Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy. AB - Fifty patients with a history of minor recurrent aphthous stomatitis were entered into a 6-month double-blind controlled trial of a gluten-free diet. After hematologic and biochemical investigations and jejunal biopsy, one half of the group was given a gluten-free diet; the other half served as controls and received a gluten-free diet supplemented by gluten given blind (control diet). Twenty-three patients completed the trial, 11 patients on a gluten-free diet, 12 on the control diet. Four of the 11 on the gluten-free diet and 7 of the 12 on the control diet reported significant benefit in terms of minor recurrent aphthous stomatitis, but there was no statistical difference between the responses. The results fail to support studies that report widespread benefit in aphthae of gluten withdrawal and suggest simply a marked placebo response in the condition. PMID- 8488029 TI - Tooth enamel dust as an asthma stimulus. A case report. AB - A case report of a first-year dental student with asthma, who experienced exacerbation of symptoms and a severe asthmatic crisis in the course of her preclinical dental training, is presented. Dust generated as a result of preparing natural teeth triggered the bronchoconstrictive response. Her subsequent medical and preventive measures are cited. This case identifies, for the first time, enamel dust as an asthma stimulus, thus serving as a precaution to prospective dental students and personnel afflicted with the disease and emphasizing the importance of effective face masks in dental laboratories during dust-generating procedures. PMID- 8488030 TI - Embryogenesis of enterocystomas-enteric duplication cysts of the tongue. AB - Enteric duplication cysts of the tongue are unusual lesions that may be confused with dermoid cysts, hemangiomas, lingual thyroid remnants, ranulas, and cystic hygromas. Two cases of lingual enteric duplications are reported in a 5-year-old boy and a 4-month-old boy. In the first case the cyst was lined by gastric-type epithelium, and in the second by colonic-type epithelium. Theories of pathogenesis of enteric duplications include development from small epithelial inclusions trapped during fusion of primordial tissues, from incomplete coalescence of lacunas that form between epithelial cells of the solid core of the developing gut, from persistence of epithelial buds within the wall of the bowel, or from nests of trapped entodermal cells. However, each of these theories presents problems with respect to lingual enteric cysts, as possible trapping of epithelium by fusing primordia does not explain the presence of heterotopic mucosa, and the tongue does not develop in the same manner as the hollow viscera. It becomes apparent therefore that enteric duplication cysts are a heterogeneous group of lesions that share some morphologic features, but perhaps not the same pathogenesis. PMID- 8488031 TI - Radiation-induced cancer risk in radiographic cephalometry. AB - The carcinogenic risks associated with the cephalometric x-ray techniques customarily used in orthodontics and oral surgery have been estimated. Lateral, posteroanterior, 45 degrees oblique, lateral temporomandibular joint tomography, basilar techniques, and commonly-used combinations were examined. Data reported in a previous article on doses absorbed by pituitary (brain), salivary, and thyroid glands were used to calculate increased risk over normal incidence using the BEIR V model. The findings are expressed in a number of graphs. Tables list the estimated percentage increase in carcinomas for several of the most often used cephalometric procedures, and compare these with the more common complete mouth (periapical) and panoramic surveys. The overall conclusion is that responsible use of cephalometric radiology adds very little to the person's carcinogenic burden. PMID- 8488032 TI - Effects of region of interest outline variations on gray-scale frequency distributions for alveolar bone. AB - Normalized cumulative percentage gray-scale distributions from digitized radiographs of dry skulls can be used to evaluate alveolar bone health. With this method, manually defined regions of interest are used to identify the area of the image to be analyzed. The purpose of this study was to determine if variations in the dimensions of the regions of interest affect the gray-scale distributions. Two approaches were used. The effect of region of interest outline variations on (1) the ability to differentiate between various sized bone chips and (2) the ability to distinguish between two groups of skulls with the alveolar bone subjectively rates as normal or diseased were investigated. Four different regions of interest, which consisted of outline and area variations to a basic region, were used. Ninety-one percent of the cumulative histograms that represented chips were sufficiently separated from nonchip plots to be distinguished. Bone health was correctly assessed with a numeric classifier for 37 of 44 quadrants, for an accuracy of 84%, a specificity of 79%, and a sensitivity of 90%. Although ROI size and shape consistency in longitudinal studies are important in radiometric analyses, small variations had minimal impact in this study. PMID- 8488033 TI - Maxillary alveolar bone imaging. Wiener filter design. AB - Optimal digital filter design is essential for noise suppression in the detection of subtle radiographic bony changes. The purpose of this study was to determine the signal (Ps) and noise (Pn) power spectra of sampled maxillary alveolar bone, to derive the optimal Wiener filter transfer function, H, from sets of Ps and Pn, and to quantify noise suppression through application of this filter. Sixteen standardized radiographs were made of five interproximal bony areas, each area from a separate dry human maxilla. The radiographs were digitized (0.02 mm/pixel resolution) and identical profiles (scan lines) generated between lead markers for each set of films. Ps was calculated from the averaged scan line of each set, Pn was calculated from the difference between the noisy images and the averaged scan line for each set, and an average maxillary H was calculated from the sets of Ps and Pn. Filtering of the 80 noisy sample radiographic profiles with H resulted in a 39% reduction in noise. Application of this digital filter should significantly improve detection of radiographic bony changes in the maxilla. PMID- 8488034 TI - Diagnostic value of bone scintigraphy in osteomyelitis of the mandible. AB - Thirty-five patients each with a tentative diagnosis of osteomyelitis of the mandible were examined with 99Tcm-labeled phosphorus compounds. The scintigraphic findings were compared with the radiographic features and related to disease stages to evaluate the diagnostic potential of bone scintigraphy in different disease stages. The scintigraphy was valuable to exclude bone tissue involvement in some patients with clinical signs and symptoms similar to those of osteomyelitis and with equivocal radiographic findings. In 13 patients with chronic osteomyelitis, scintigraphy revealed a larger extent of the lesion than the radiography. In lesions with permeated bone destructions with penetration of the cortex, the uptake of 99Tcm was higher than in lesions with a motheaten or sclerotic appearance. This study supports the view that 99Tcm-bone scintigraphy is a useful tool at various stages of osteomyelitis, that is, in its early detection, in the treatment or biopsy planning, and in the evaluation of the efficacy of treatment. PMID- 8488035 TI - Pathologic deviation of the parotid duct. PMID- 8488036 TI - Bilateral hypoplasia of mandibular condyles in Hurler's syndrome. PMID- 8488037 TI - Bullet discovered on a panoramic radiograph. PMID- 8488038 TI - Swallowed hypodermic needle in the stomach. PMID- 8488039 TI - Quality measurement, management, and reimbursement in today's health care environment. PMID- 8488040 TI - Quality, cost, and the public's right to know: what is needed to make informed decisions? PMID- 8488041 TI - Outcomes are in the eye of the "health seeker". PMID- 8488042 TI - The leader's role in implementing quality improvement: walking the talk. PMID- 8488043 TI - Overcoming the barriers to implementation of TQM/CQI in hospitals: myths and realities. AB - Many health care organizations are attempting to rapidly implement total quality management (TQM) and continuous quality improvement (CQI) philosophies and concepts. In the case of hospitals, a number of issues resulting from traditional organizational design and management practices as well as the characteristics of health care professionals pose significant challenges to rapid implementation. Recognizing and developing strategies to address these challenges, along with realizing that TQM and CQI represent viable processes for conducting organizational "preventive maintenance," may help in changing the focus of quality assessment and enhancement initiatives from processes that are "broken" to processes that should be "fixed" before they "break." This article discusses strategies for overcoming some of the major barriers and challenges to successful TQM and CQI implementation to the hospital setting. PMID- 8488044 TI - Patients' good and bad surprises: how do they relate to overall patient satisfaction? AB - The literature documents little research regarding patients' good and bad surprises in the hospital. Such experiences may inform a patient's future decisions about recommending or returning to the hospital. Utilizing a database of survey respondents, the authors conducted qualitative and quantitative analyses of patients' self-reported surprises about their hospital stay and the relationship between those surprise experiences and their overall feelings of satisfaction. Analysis of these data shows that patients do experience surprises during their hospital stays, that specific events are associated with these surprises, and that these surprises influence patient satisfaction. These results suggest that in order for health care providers to continuously improve and meet patients' needs and expectations, providers must determine steps to take to delight their patients, to avoid patient disappointments, and to meet patients' basic expectations. PMID- 8488045 TI - Too many managers: major threat to CQI in hospitals. AB - Some hospitals are rushing into continuous quality improvement (CQI) without understanding the pitfalls, one of which is the issue of empowerment. To prevent middle managers from inappropriately reinvolving themselves in the activities of empowered front-line workers, empowerment of employees must be accompanied by a substantial decrease in the number of middle managers. Despite its importance, however, this move is rarely undertaken for two reasons: first, a failure to analyze management "spans of control" in the context of empowerment; second, the fear that staff reductions will imperil the CQI implementation. This article presents case studies of effective and ineffective management to demonstrate that without span of control adjustments, empowerment will fail, whereas appropriate adjustments will allow it to succeed even beyond expectations. PMID- 8488046 TI - Debating Medicare participation. PMID- 8488047 TI - Questioning KePRO's methods. PMID- 8488048 TI - What physicians need to know: new state CON law. AB - In past years, Pennsylvania's certificate of need law applied mostly to hospitals and other health care institutions. But the commonwealth's new law also targets physicians--especially those planning to establish MRI or ambulatory surgical facilities. PMID- 8488049 TI - A matter of cost control: comparing priorities for Pennsylvania. PMID- 8488050 TI - Physicians speak out on reform concerns. AB - Physicians have taken an aggressive role testifying at hearings on a health care reform plan proposed late last year by the governor's Economic Development Partnership (EDP). The State Society has offered substantial support to those physicians and closely monitored each event. This article briefly overviews the proposed plan and includes excerpted testimonies submitted to the EDP by four concerned physicians. PMID- 8488051 TI - Society endorses AIDS guidelines. PMID- 8488052 TI - Building blocks of the public health system. Interview by Juli C. McGreevy. PMID- 8488053 TI - Protecting your practice from insurance defaults. PMID- 8488054 TI - Self-referral: a matter of ethics? PMID- 8488055 TI - [Species of the genus Koellikeria--parasites of Pacific Ocean sea breams]. AB - Rediscriptions and original figures of the trematodes Koellikeria filicollis and K. shimai, parasites of sae breams (Brama brama, B. japonica) from the Pacific with the data on localization and distribution of these species, have been given. K. filicollis is a very polymorphic form, which changes during its development. Didymozoon shimai Pozdnyakov, 1985 is transferred to the genus Koellikeria. PMID- 8488056 TI - [The effect of temperature and lighting on the biology of Philophthalmus rhionica (Trematoda) miracidia]. AB - The influence of temperature and illumination on the process of mature eggs production from the uterus of adults of Philophthalmus rhionica and on the hatching of miracidia has been investigated. Illumination in contrast to the temperature does not play a great role. The temperature factor also defines the larvae duration life and the velocity of their swimming and has some influence on the invasiability of miracidia, which is enhanced with heating. The data received does not confirm the position of Semenov (1977) that in the presence of simultaneous influence of light and temperature the influence of the former factor upon the infection of the fresh-water mollusk Melanopsis praemorsa is more significant. PMID- 8488057 TI - [The population level and distribution of ectoparasites in carp]. AB - The abundance and the distribution of Dactylogyrus extensus and Ichthyophthirius multifiliis on gills of two-years old carps have been investigated. It has been established that at least there are five groups, which differs from each other on the asymmetry of infection. PMID- 8488058 TI - [Specialization, progress and regress in endoparasites]. PMID- 8488059 TI - Microtubular organization visualized by immunofluorescence microscopy during erythrocytic schizogony in Plasmodium falciparum and investigation of post translational modifications of parasite tubulin. AB - We describe a novel procedure for the immunofluorescent investigation of Plasmodium falciparum. This has allowed us to visualize clearly microtubular structures and their changing conformation through the erythrocytic cell-cycle, to the stage of cytodifferentiation leading to merozoite release. The images of spindle development we observed, together with an analysis of nuclear body numbers in large numbers of parasites, indicate that there is an apparent asynchrony in chromosomal multiplication within a single parasite. Using antibodies specific for post-translational modification of alpha-tubulin, we also demonstrate that the C-terminal tyrosine-containing epitope of P. falciparum alpha-tubulin I is similar to that of other organisms. Lysine-40 in the same molecule, a target for highly specific in vivo acetylation in some organisms, is unmodified in the blood stages we examined here. After in vitro acetylation of this residue, however, the epitope to which it contributes was recognized by antibody, showing that the conformation of this part of the molecule is also conserved, despite a lack of primary sequence homology immediately downstream of the target lysine residue. PMID- 8488060 TI - The effect of Giardia lamblia trophozoites on trypsin, chymotrypsin and amylase in vitro. AB - Giardia lamblia localize and multiply in the small intestine and may cause acute or chronic diarrhoea with malabsorption of fat, protein and other nutrients. Abnormal pancreatic function has been documented in giardiasis and trophozoites directly inhibit pancreatic lipase activity in vitro. The aim of this study was to examine the effect of Giardia trophozoites on pancreatic trypsin, chymotrypsin and amylase activity in vitro. Axenically cultured Giardia trophozoites (Portland 1 stock) were incubated with a range of concentrations of trypsin, chymotrypsin and amylase and enzyme activity assayed over time. Tryptic activity was decreased after incubation with Giardia trophozoites. This reduction was time dependent and linear over the incubation period of 2 h. At a trypsin concentration of 18 BAEE units/ml, there was a 35.5 +/- 4% reduction in enzyme activity after 2 h compared to controls. The total amount of activity lost was proportional to the initial trypsin concentration up to 185 BAEE units/ml. At this initial concentration, the activity was reduced by 46.5 +/- 3 units/ml after 2 h. Above this concentration, little further loss of enzyme activity was seen. To investigate the nature and specificity of this effect, similar experiments were conducted using killed trophozoites and with a related protozoan, Trichomonas vaginalis. No loss of enzyme activity was evident. Media previously incubated for 2 h with trophozoites did not diminish tryptic activity. Trophozoites had no effect on chymotrypsin or amylase activities over the range of concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488061 TI - In vitro isolation and characterization of a Neospora sp. from aborted bovine foetuses. AB - A Neospora sp. was isolated from the brains of two aborted bovine foetuses and grown continuously in vitro in bovine cell cultures. A comparison of the antigenic reactivity of in vitro cultivated tachyzoites with polyclonal antisera to Neospora caninum, Hammondia hammondi or Toxoplasma gondii revealed that the bovine protozoal isolates were similar to N. caninum and antigenically distinct from T. gondii. Tachyzoites of both bovine isolates had similar ultrastructural features, including an apical polar ring, conoid, electron-dense rhoptries and micronemes. The orientation of the micronemes, presence of micropores and a large number of electron-dense granules in the posterior portion of the bovine isolate tachyzoites differed from previous descriptions of N. caninum in vivo. Tachyzoites of the bovine isolates were ultrastructurally more similar to in vitro cultivated N. caninum tachyzoites than to tachyzoites of T. gondii or H. hammondi. The antigenic and ultrastructural similarities between N. caninum and the protozoal parasites isolated from aborted bovine foetuses in this study support the proposition that these parasites belong to the genus Neospora. PMID- 8488062 TI - Preliminary analysis of the transmission dynamics of Theileria parva in eastern Africa. AB - Two mathematical models are developed that investigate the transmission dynamics of Theileria parva by the ixodid tick Rhipicephalus appendiculatus to cattle in endemically stable areas. A method of estimating the rate of infection to cattle of T. parva at the endemically stable state is given. Empirical estimates of all the parameters in the model are available. The degree to which animals that have recovered from theileriosis (the 'carrier' state) are able to transmit the infection to tick nymphs or larvae is a crucial determinant of the dynamics of infection in a herd. Two control methods influencing the transmission of infection are considered--infection and treatment immunization and the reduction in tick feeding by acaricide application. The impact of each method on the transmission of infection is evaluated. Future developments and the data required to predict the dynamics of T. parva infections in cattle and ticks are discussed. PMID- 8488063 TI - Decoy effect and host infection by miracidia within snail communities. AB - The effect of experimental non-host snail (NHS) communities on the infection of Lymnaea truncatula with Paramphistomum daubneyi and Fasciola hepatica miracidia was studied. The results obtained indicated that NHS had variable effects on basic population parameters of host infection. Specifically, NHS were able to produce aggregation of sporocyst number/snail in the experimental host populations. Proposed hypotheses for decoy effect mechanisms failed to explain completely the experimental results. A new mechanism is suggested, based on a distance response of miracidia to snail chemo-attractants, to explain effects of NHS on miracidial host finding behaviour. It is assumed that miracidia have evolved the ability to discriminate among individual snail chemical attractants in a community already at a distance. This attribute of miracidial behaviour allows NHS to induce variations in the effectiveness of individual host localization by miracidia. The resulting aggregation of successful infections/host is assumed to be the specific component of snail decoy effect at the community level. It was also established that NHS affected trematode reproduction in the host inducing a compensatory increase in the intramolluscan population. Intraspecific competition among developmental stages is suggested to be the mechanism of this compensatory reaction. PMID- 8488064 TI - Field trials in the control of Opisthorchis viverrini with an integrated programme in endemic areas of northeast Thailand. AB - A control programme of opisthorchiasis was carried out for three years in three villages of northeast Thailand in order to compare the effectiveness of two intervention measures. The intervention measures employed were to give praziquantel treatment to all infected people either once (village I) or twice (village II) per year with the integration of regular health education and sanitation improvement. A control village (village III) received no intervention during the study. Sampling of the population in these villages to estimate prevalence, intensity, reinfection and incidence of infection as well as knowledge of opisthorchiasis and number of latrines was performed at 6 monthly intervals throughout the duration of the study. At the initial assessment, there were no significant differences in the prevalence and intensity of infection of villages I and II. Both values were greatly reduced when assessed 6 months after the initiation of treatment, and the decrease in prevalence and intensity of infection did not differ between village I and II. The control village (village III), during the first 2 years, exhibited slight variation in the prevalence and intensity, and these decreased considerably in the third year of the study. The reinfection rate per 6 months in villages I and II was nearly equal. The incidence rate per 6 months in the two treated villages was lower than that of the control village. Marked improvement in knowledge of opisthorchiasis, behavioural changes of eating raw fish and increased numbers of latrines was evident in all of the villages during this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488065 TI - An IgG (Fc gamma)-binding protein of Taenia crassiceps (Cestoda) exhibits sequence homology and antigenic similarity with schistosome paramyosin. AB - Previous studies from this laboratory have suggested the presence of antibody binding molecules on the surface of Taenia crassiceps metacestodes. We now report the purification of a T. crassiceps Fc gamma-binding protein which has an equivalent molecular size (96 kDa), is antigenically similar and exhibits significant amino acid sequence homology to schistosome paramyosin. The similarities in molecular weight of the T. crassiceps protein, Schistosoma mansoni paramyosin and antigen B of T. solium, the close amino acid sequence homologies between the T. crassiceps protein and S. mansoni paramyosin and between S. mansoni paramyosin and antigen B of T. solium, and the antigenic similarity of the T. crassiceps protein with paramyosin indicates that this family of platyhelminth proteins are closely related. The known characteristics of T. solium antigen B (collagen binding affinity; disruption of complement function) and the Fc gamma-binding activity of the T. crassiceps molecule suggests that this class of proteins may be multifunctional, fulfilling not only a structural role but also as components interacting with the host immune system to increase parasite survival. PMID- 8488066 TI - The expulsion of Echinostoma trivolvis: worm kinetics and intestinal cytopathology in conventional and congenitally athymic BALB/c mice. AB - The infectivity and distribution of Echinostoma trivolvis were studied in male, conventional and congenitally athymic nude mice, each infected with 30 metacercarial cysts. In conventional mice, worm recoveries at 6 and 8 days post exposure were 58.3 and 54.0%, respectively. Worm recovery declined to 44.0% by day 10, to 4.3% by day 13, and 0% by day 17. In athymic mice, worm recoveries at 6 and 8 days post-exposure were 61.7 and 36.3%, respectively. Worm recovery declined to 27.7% by day 10, to 0.7% by day 13, and 0% by day 17. The distribution of worms demonstrated a posteriad migration over time in both groups. Kinetic changes in the number of goblet and mucosal mast cells in the upper ileum of mice infected with E. trivolvis were examined. In conventional mice, the number of goblet cells increased rapidly to reach a peak at day 13 and then declined gradually. The number of goblet cells in athymic mice also increased to reach a peak at day 13, and then declined rapidly. However, the number of goblet cells in athymic mice was always less than that in conventional mice. The mast cell number in infected conventional mice increased rapidly to reach a peak at day 17 and then declined. There was no increase in the mast cell number of infected athymic mice throughout the experiment. Whereas common pathological changes occurred in the intestines of both mice groups infected with echinostomes some ultrastructural differences were observed in the gut epithelial cells of conventional versus athymic mice. PMID- 8488067 TI - Temporal changes in glucose and carbohydrate metabolism in the oncospheres of the cyclophyllidean tapeworm, Hymenolepis diminuta. AB - When incubated in vitro for 24 h, oncospheres of Hymenolepis diminuta absorb and metabolize radioactive glucose. Between 0 and 12 h post-activation, oncospheres absorb glucose, but glucose is neither metabolized into other carbohydrates nor incorporated into the ethanol-precipitable fraction (which would contain glycogen). Between 12 and 24 h post-activation glucose is incorporated into a number of higher molecular weight carbohydrates that are demonstrable in ethanol extracts of the larvae, as well as the incubation media. Furthermore, measurable amounts of radioactivity are incorporated into the ethanol-precipitable carbohydrate fraction of oncospheres. To determine if these temporal changes in carbohydrate metabolism occurred spontaneously following activation, oncospheres were pre-incubated for 12 h (0-12 h post-activation) in the absence or presence of glucose, and then transferred to media containing radioactive glucose for an additional 12 h (12-24 h post-activation). In these latter experiments, glucose absorption and metabolism between 12 and 24 h post-activation were virtually identical to glucose metabolism in oncospheres that were incubated in radioactive glucose for 0-12 h immediately following activation. Thus, these data do not support the hypothesis that the temporal shift in carbohydrate metabolism occurs spontaneously. PMID- 8488068 TI - Intestinal helminth communities of the long-finned pilot whale (Globicephala melas) off the Faroe Islands. AB - The intestines of 170 long-finned pilot whales, Globicephala melas, caught off the Faroe Islands (N.E. Atlantic) were examined for helminth parasites. Eight species were detected but only 4 occurred in at least 10% of the sample. No core or recurrent group of species were identified and no correlations between abundances of species were significant. Diversity values were far below those reported for other endotherms. Colonization by helminths was random, whales not being readily colonized. These features point to largely unpredictable, isolationist infracommunities, there being little potential for inter-specific interactions. Older hosts tended to harbour more diverse infracommunities, offering more opportunities for such interactions. Two hypotheses, which might also apply to other cetaceans, are proposed to account for the depauperate helminth communities of the pilot whale: (i) some ancestral helminth species failed to adapt their cycles to the marine habitat and (ii) the hosts' isolation from land prohibited new infections with helminths of mammals. PMID- 8488069 TI - Aquatic pollution: effects on the health of fish and shellfish. AB - As there is little evidence of pollution affecting the health of fish and shellfish on a global scale, this paper attempts to put into perspective the pollution/fish disease relationship by reviewing examples of studies and reports in the historic and current literature. Although there is no dispute that pollution can affect the aquatic organisms under laboratory conditions and may be responsible for the decline of populations of such animals in some inland waters and some estuaries, most of the evidence for pollution causing or increasing disease in fish in open waters is circumstantial. Historical data proves that almost all fish and shellfish diseases known today have been described since the end of the last century. However, it is also known that water pollution, especially in inland waters, has for the past 400-500 years been the result of urbanization and industrialization. This has resulted in some major rivers becoming devoid of or deficient in fish stocks. The concern that pollution may influence the health status of fish and shellfish stocks has increased over the past 20 years. Initial attention was paid to epidermal diseases, including fin rot in demersal fish, and protozoan diseases in molluscs in the heavily polluted bays and estuaries in North America. As the interest in this subject spread, it became political, and often controversial, especially amongst the North Sea countries. The disagreements have largely been settled amongst scientists because international bodies, such as the International Council for Exploration of the Sea (ICES), established workshops to investigate sampling methods and disease reporting techniques. Recommendations from those workshops have contributed to some form of standardization for field work and the subject, although largely subjective, has some objective approaches which are described. As there are variable, interacting biological and physical influences in the aquatic environment, it is difficult to establish the background prevalences of diseases in populations of fish and shellfish. Examples of the influences of climatic changes are presented, and these show that short-term catastrophes can be directly related. However, a more long-term problem is water acidification resulting largely from anthropogenic activities. In parts of Scandinavia this has, and is, leading to decimation of fish stocks in inland waters. In general, diseases in fish and shellfish are very localized, but there is concern amongst scientists that certain cancers, especially liver tumours, occurring in demersal fish inhabiting polluted estuarine and coastal waters, are related to the release of chemicals, e.g. hydrocarbons, pesticides and heavy metals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488070 TI - Depletion of the ozone layer: consequences for non-infectious human diseases. AB - Stratospheric ozone depletion threatens to increase exposure to ultraviolet (UV) radiation which is known to be a factor in a number of diseases. There is little doubt that cumulative exposure to UV radiation is important in the aetiology of non-melanoma skin cancers. Evidence is also strong for a link with cutaneous malignant melanoma, although here it appears to be intermittent intense exposure that is most damaging. More controversial is the view that exposure to solar radiation is a significant factor in ocular damage, particularly in the formation of cataracts. Earlier studies pointing to such an effect have been criticized and alternative aetiological hypotheses have been proposed. However, other studies do show an effect of UV exposure on cortical cataract. Concern is also growing that UV may be capable of activating viruses and have immunological effects that might exacerbate infectious disease. Very worrying is the possibility that UV exposure can activate the human immunodeficiency virus which might accelerate the onset AIDS. Any such health effects that have been observed in human populations are the result of exposure to existing, naturally occurring levels of UV radiation. There is, therefore, great concern about the possible exacerbation of these impacts as a result of increased exposure to UV radiation associated with stratospheric ozone depletion. However, any assessment of the nature and scale of such impacts on human health has to deal with several major problems and these are the focus of this paper. There are uncertainties about recent trends in stratospheric ozone and problems in the prediction of future changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488071 TI - Mankind and plants: the need to conserve biodiversity. AB - Only green plants can convert the single carbon units of atmospheric carbon dioxide into the multi-carbon organic molecules on which all forms of life depend. Only green plants can provide the oxygen required by man and other aerobic organisms. In addition to his basic need for preformed organic molecules and oxygen, man also depends on plants to provide him, directly or indirectly, with an array of specific compounds such as vitamins and essential amino acids. Inadequate supplies of these may hinder growth and development or give rise to well defined deficiency diseases. At the present time information concerning the distribution and concentrations of such essential nutrients in plants is largely restricted to those plants that are already used as human foods. Nothing or virtually nothing is known about the chemical composition of approximately 250 000 wild and little-used species. Amongst these there may be many that could provide us with cheap and plentiful new sources of essential nutrients that could be of enormous benefit to those suffering not only from full-blown deficiency diseases but also suffering sub-normal health due to partial deficiencies. The destruction of much of the world's wilderness areas has already deprived us of the opportunity to evaluate the contributions that a great many plant species might have made towards the elimination of deficiency diseases. Many plants used as human foods contain compounds that are toxic to man. If intake is sufficiently high, these toxins may cause disease. Breeding programmes designed to eliminate toxins from crops species or reduce their concentrations to acceptable levels depend on genetic variability within the species or the possibility of producing hybrids with the desired characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488072 TI - Global warming: trends and effects. AB - As animals we have been a remarkably successful species; but also as animals we are vulnerable to environmental, in particular climate change. Such change is accelerating as a result of human activity, and global warming may already be taking place. Although we can foresee the trends, we cannot yet be specific about the results. Change usually proceeds by steps rather than gradients. But warming would probably include new risks to human health and contribute to an increase in human displacement. Of course climate change is only one among other complex problems facing human society, but it is closely related to them all, including population increase, environmental degradation and loss of biodiversity. We cannot prevent global warming but we can anticipate and mitigate some of its worst effects. Peoples and governments still need persuading of the need for action and of the magnitude of the issue at stake. PMID- 8488073 TI - Deforestation: effects on vector-borne disease. AB - This review addresses changes in the ecology of vectors and epidemiology of vector-borne diseases which result from deforestation. Selected examples are considered from viral and parasitic infections (arboviruses, malaria, the leishmaniases, filariases, Chagas Disease and schistosomiasis) where disease patterns have been directly or indirectly influenced by loss of natural tropical forests. A wide range of activities have resulted in deforestation. These include colonisation and settlement, transmigrant programmes, logging, agricultural activities to provide for cash crops, mining, hydropower development and fuelwood collection. Each activity influences the prevalence, incidence and distribution of vector-borne disease. Three main regions are considered--South America, West & Central Africa and South-East Asia. In each, documented changes in vector ecology and behaviour and disease pattern have occurred. Such changes result from human activity at the forest interface and within the forest. They include both deforestation and reafforestation programmes. Deforestation, or activities associated with it, have produced new habitats for Anopheles darlingi mosquitoes and have caused malaria epidemics in South America. The different species complexes in South-East Asia (A. dirus, A. minimus, A. balabacensis) have been affected in different ways by forest clearance with different impacts on malaria incidence. The ability of zoophilic vectors to adapt to human blood as an alternative source of food and to become associated with human dwellings (peridomestic behaviour) have influenced the distribution of the leishmaniases in South America. Certain species of sandflies (Lutzomyia intermedia, Lu. longipalpis, Lu. whitmani), which were originally zoophilic and sylvatic, have adapted to feeding on humans in peridomestic and even periurban situations. The changes in behaviour of reservoir hosts and the ability of pathogens to adapt to new reservoir hosts in the newly-created habitats also influence the patterns of disease. In anthroponotic infections, such as Plasmodium, Onchocerca and Wuchereria, changes in disease patterns and vector ecology may be more difficult to detect. Detailed knowledge of vector species and species complexes is needed in relation to changing climate associated with deforestation. The distributions of the Anopheles gambiae and Simulium damnosum species complexes in West Africa are examples. There have been detailed longitudinal studies of Anopheles gambiae populations in different ecological zones of West Africa. Studies on Simulium damnosum cytoforms (using chromosome identification methods) in the Onchocerciasis Control Programme were necessary to detect changes in distribution of species in relation to changed habitats. These examples underline the need for studies on the taxonomy of medically-important insects in parallel with long-term observations on changing habitats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488074 TI - Monitoring trypanosomiasis in space and time. AB - The paper examines the possible contributions to be made by Geographic Information Systems (GIS) to studies on human and animal trypanosomiasis in Africa. The epidemiological characteristics of trypanosomiasis are reviewed in the light of the formula for the basic reproductive rate or number of vector borne diseases. The paper then describes how important biological characteristics of the vectors of trypanosomiasis in West Africa may be monitored using data from the NOAA series of meteorological satellites. This will lead to an understanding of the spatial distribution of both vectors and disease. An alternative, statistical approach to understanding the spatial distribution of tsetse, based on linear discriminant analysis, is illustrated with the example of Glossina morsitans in Zimbabwe, Kenya and Tanzania. In the case of Zimbabwe, a single climatic variable, the maximum of the mean monthly temperature, correctly predicts the pre-rinderpest distribution of tsetse over 82% of the country; additional climatic and vegetation variables do not improve considerably on this figure. In the cases of Kenya and Tanzania, however, another variable, the maximum of the mean monthly Normalized Difference Vegetation Index, is the single most important variable, giving correct predictions over 69% of the area; the other climatic and vegetation variables improve this to 82% overall. Such statistical analyses can guide field work towards the correct biological interpretation of the distributional limits of vectors and may also be used to make predictions about the impact of global change on vector ranges. Examples are given of the areas of Zimbabwe which would become climatically suitable for tsetse given mean temperature increases of 1, 2 and 3 degrees Centigrade. Five possible causes for sleeping sickness outbreaks are given, illustrated by the analysis of field data or from the output of mathematical models. One cause is abiotic (variation in rainfall), three are biotic (variation in vectorial potential, host immunity, or parasite virulence) and one is historical (the impact of explorers, colonizers and dictators). The implications for disease monitoring, in order to anticipate sleeping sickness outbreaks, are briefly discussed. It is concluded that present data are inadequate to distinguish between these hypotheses. The idea that sleeping sickness outbreaks are periodic (i.e. cyclical) is only barely supported by hard data. Hence it is even difficult to conclude whether the major cause of sleeping sickness outbreaks is biotic (which, in model situations, tends to produce cyclical epidemics) or abiotic.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488075 TI - Urbanization and human health. AB - Urbanization involves a physical change in which increasing proportions of populations live in urban settings, however defined. It also implies considerable changes in the ways in which these people live, how they earn their livelihoods, the food which they eat, and the wide range of environmental factors to which they are exposed. There is another underlying assumption that, increasingly, urban populations will be more healthy than their rural counterparts and that higher levels of urbanization will equate with better health status. This paper discusses some of the assumptions underlying this contention. It takes issue with certain of them, particularly the assumption that urbanization affects the health of all residents equally. It is manifestly evident that in many cities, particularly in the developing world, the poor are exposed to greater risks and have much lower health status than their richer neighbours. In addition, whilst urban residents may theoretically have a better access to health care and services than do residents in many rural areas, and whilst many indicators of health do appear better in more highly urbanized societies than ones less so, there are caveats. The paper introduces the concept of epidemiological transition, which suggests that, whilst life expectancy might be higher in many urbanized countries and in certain cities, the inhabitants are often merely suffering from different forms of ill-health, often chronic or degenerative, rather than infective. In certain cities in middle-income countries, residents, particularly the poor, are exposed to a double risk of both infection and chronic degenerative ailments. The paper concludes with a consideration of more general recent statements from the World Health Organization among others, on the impact of urbanization on health. The 'Healthy Cities' project is also discussed. WHO identifies a range of general determinants of urban health: physical, social, cultural and environmental. Many represent the by-products of modernization and especially industrialization. It is emphasized that urbanization, and the concentration of human beings into new areas in particular, can bring exposure to new risk factors for large numbers of people. The growth of infectious and parasitic disease in some urban settings must therefore be recognized, as must the emergence of chronic diseases, with the concomitant need for investment in new types of health and social care. However, a number of constraints militate against the achievement of improved urban health, especially in developing countries.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488076 TI - Tumor-like intravascular proliferations of the stroma in adenomyosis. AB - Two hundred cases of adenomyosis have been studied in order to clarify the origin and significance of intravascular endometrial tissue in adenomyosis. A tumor-like intravascular proliferation of the adenomyotic stroma (IVSP) has been found in 17.5% of the cases. An endolymphatic proliferation (35 cases) was occasionally accompanied by an intravenous proliferation (3 cases). IVSP originated from a perivascular stromal proliferation (PVSP) and occurred only in deep adenomyosis. IVSP was focal and showed no atypia. It was significantly most frequent in patients 50-53 years of age and more frequent in patients up to 53 years than in those over 53. The frequency of occurrence of PVSP and IVSP was related to the histologic features of adenomyosis and the endometrium and was highest in hyperplastic adenomyosis and in adenomyosis accompanied by hyperplasia of the endometrium. The study suggests that PVSP and IVSP develop in the areas of adenomyotic stroma stimulated by estrogen and nonresponsive to progesterone. The differential diagnosis of tumor-like and sarcomatous IVSP, and histogenesis of adenomyosis are discussed. PMID- 8488077 TI - Porphobilinogen deaminase activity in malignant proliferative disorders of the lymphatic system and bone marrow. AB - Porphobilinogen deaminase activity was studied in the erythrocytes of 73 women and 35 men with various malignant proliferative disorders of the lymphatic system and bone marrow, and, for comparison, in the erythrocytes of 34 women and 14 men with non malignant diseases of the haemopoietic system, and in those of 20 healthy women and 20 healthy men. The activity of the enzyme was determined by the Hsiao et al. method, using porphobilinogen as a substrate. Statistical analysis showed a significant decrease of porphobilinogen deaminase activity in the erythrocytes of men with Hodgkin's disease and women with plasmocytoma and with myeloblastic leukemia; an increased activity of the studied enzyme was found only in men with lymphocytic leukemia. PMID- 8488078 TI - [Transmissible and non-transmissible brain amyloidoses: neurodegenerative disorders of different etiologies and the same pathogenesis]. AB - I report here the molecular, ultrastructural and immunohistochemical similarities between transmissible (scrapie, Creutzfeldt-Jakob disease and Gerstmann Straussler-Scheinker syndrome) and non-transmissible (Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis--Dutch (HCHWA-D) and Icelandic (HCHWA-I) types) brain amyloidoses. The central pathogenic event in both types of amyloidoses is a synthesis and a processing of amyloid precursor followed by an accumulation of a final deposit. PrPc and APP are amyloid precursors and PrPsc and beta-A4 are final deposits in transmissible and nontransmissible cerebral amyloidoses of Alzheimer's disease type, respectively. In HCHWA-I, cystatin C serves the role of the amyloid precursor protein. The amyloid plaque composed of a different proportions of amyloid fibers, dystrophic neurites and astrocytes and microglia cells is the crucial neuropathological entity. The role of microglial cell as amyloid producer/processor cell seems to be analogous in both types of amyloidoses. The impairment of slow axoplasmic transport which leads to the accumulation of neurofilament triplet protein in the transmissible and tau protein in the non-transmissible cerebral amyloidoses causes the development of dystrophic neurites and neuropil threads. The other elements of neuropathology like Hirano bodies and granulovacuolar degeneration may be only secondary and non specific phenomena. PMID- 8488079 TI - [PATHOLOGIST --software package for database management systems in pathology]. AB - This article summed up 4 years experiences in the creation and working with software package for collection, processing and storage of data in the form of standard database. Software package--PATHOLOGIST--can be implemented on microcomputer compatible with IBM PC. This package manages 92 relative databases in the order to gather all possible information about performed histological, cytological, immunological examinations as well as autopsy. PMID- 8488080 TI - Cytodiagnosis of Hodgkin's disease in bronchial brush smears. AB - A case of 65 years of old female in which Reed-Sternberg cells were found in brush specimens from bronchial mucosa is reported. Histopathologic specimens from bronchial mucosa and lymph nodes were estimated too. We would like to direct attention to the necessity differential diagnosis Reed-Sternberg cells with adenocarcinoma cells in brush specimens from bronchial mucosa. PMID- 8488081 TI - The malignant form of calcifying odontogenic cyst. A case report. AB - A rare case of the malignant form of Gorlin's cyst is reported in a 42-year-old woman. The neoplasm developed in the right maxilla, infiltrated the anterior wall and roof of the sinus and grew into the nasal cavity. Based upon literature data we characterized various clinical and histological forms of Gorlin's cyst (calcifying odontogenic cyst). PMID- 8488082 TI - Inflammatory pseudotumor of spleen. AB - A case of inflammatory pseudotumor of the spleen in a 78-years-old woman is presented. The diagnosis was established histologically. This is the ninth case of this rare entity described in the literature. The differential diagnosis of inflammatory pseudotumor especially with primary lymphoma of the spleen is discussed. PMID- 8488083 TI - Relation between cardiovascular pathologic conditions and malignant tumours as seen by pathologist. II. Myocardial infarct and coronary atherosclerosis in the population suffering from malignant neoplasm as seen by pathologist. AB - In the autopsy material of 2932 men and 3051 women the frequency of fresh myocardial infarct and the severity of coronary atherosclerosis were highly significantly lower in the population suffering from malignancies than in that free of cancer. Lower frequency of myocardial infarct seems to result from lower severity of coronary atherosclerosis. The incidence rate of myocardial infarct was also significantly lower in the cancer--bearing group when both compared populations showed identical, severe (grade 4) coronary atherosclerosis. This observation seems to indicate lesser contribution of coronary spasm in cancerous population and justifies the discussion of possible significance of EDRF (endothelium-derived relaxing factor) and catecholamines. PMID- 8488084 TI - Water handling in Caco-2 cells: effects of acidification of the medium. AB - Caco-2 cells were cultured on permeable supports. At confluence the minute-by minute net water movement (Jw) was automatically recorded. Simultaneously, unidirectional [14C]mannitol, 22Na+, and/or 36Cl- fluxes and transepithelial resistances were measured. The water and mannitol permeabilities went progressively down between 9 and 16 days after seeding and then stabilized. In this last condition the hydrostatic permeability coefficient (Phydr) was 2.67 +/- 0.31 cm s-1 while the osmotic permeability coefficient (Posm) was 0.0017 +/- 0.0004 cm s-1. Phydr but not Posm was dependent on the temperature and on the presence of Na+ in the medium. A net secretory Jw was observed 16 days after seeding, in the absence of any osmotic, hydrostatic or chemical gradient. This secretory Jw was associated with net Cl- (1.43 +/- 0.43 muequiv h-1 cm-2) and Na+ (1.05 +/- 0.35 muequiv h-1 cm-2) secretions. Amiloride reduced, in open-circuit conditions, both Na+ and Cl- apical to basal fluxes, thus enhancing the net Na+ and Cl- exit. Acidification of the medium (pH 6.2) reversibly increased water and mannitol permeabilities in 10-day-old cultures. In 16-day-old cultures the same shift in medium pH did not change mannitol permeability, while stimulating water secretion. These results, obtained in the absence of supracellular structures (villae, crypts) and subepithelial components (muscular, vascular and conjunctive tissues) indicate that paracellular and transport-associated water pathways are sensitive to changes in the pH of the medium in Caco-2 cell layers. PMID- 8488085 TI - A force transducer and a length-ramp generator for mechanical investigations of frog-heart myocytes. AB - An apparatus for studying the mechanics of isolated frog heart myocytes is described. The cells are held horizontal in a through of Ringer solution by means of two suction micropipettes. Myocyte force is measured with an opto-electronic system recording the deflection of the tip of one micropipette, which acts as a cantilever force probe. The force probes are selected for compliance according to the force a myocyte is expected to develop in a given condition, so as to limit myocyte shortening during force development to no more than 1% of the slack cellular length (l0). The other micropipette, which is stiff relative to the forces measured, is mounted on an electromagnetic-loudspeaker motor by which controlled-velocity length changes, of preset size and in either direction, are imposed on myocytes. The force transducer has a sensitivity of 5-10 mV/nN, with a frequency response of 700-900 Hz in Ringer solution and a resolution of 0.5-1 nN. The motor with a suction micropipette can complete controlled-velocity length ramps within 1.5-2.0 ms, across a range of +/- 100 microns at a resolution of 8.0 nm. These values correspond, for frog-heart myocytes 200 microns and 400 microns long, to 25%-50% l0 and 0.002%-0.004% l0 respectively. PMID- 8488086 TI - Temporal response properties of lumbar-projecting vestibulospinal neurons to roll tilt in decerebrate cats. AB - In decerebrate cats, rotation about the longitudinal axis of the animal, leading to sinusoidal stimulation of labyrinth receptors, produces a tonic contraction of limb extensors during side-down tilt (alpha responses) and of dorsal neck extensors during side-up tilt (beta responses). These changes in posture are mediated, at least in part, by lateral vestibular nucleus (LVN) neurons, with response characteristics to stimulation of macular and/or canal receptors that have so far been evaluated at the level of either unidentified vestibulospinal (VS) neurons or vestibulo-collic neurons projecting to the upper cervical cord. In the present study we investigated the dynamics of the responses of VS neurons projecting to the lumbosacral segments of the spinal cord to increasing frequencies of tilt (from 0.026 to 0.32 Hz, +/- 10 degrees). All the recorded units showed an average phase lead with respect to position of +25.6 +/- 5.5 degrees (SE) at the tilt frequency of 0.026 Hz. Most of these neurons (n = 32) were particularly activated during side-down tilt (alpha responses) and showed either a stable phase or an increase in phase lead of the responses with increasing frequency of tilt. At the tilt frequency of 0.026 Hz, the smaller the phase lead of the responses, the larger was the response gain. Moreover, the smaller the phase lead of the responses at that frequency of tilt, the smaller the increase in gain but the larger was the increase in lead of the responses obtained by increasing the stimulation frequency up to 0.32 Hz. Through this set of finely organized changes in unit response characteristics, the overall output of this population of neurons increased, while the phase angle of the responses reached the mean value of +64.9 +/- 2.6 degrees (SE), thus becoming more related to the velocity than to the positional signal. The remaining units (n = 7), which were mainly activated during side-up tilt (beta responses), displayed an increase in phase lag of the responses to increasing frequency of stimulation, which reached the mean value of -118.9 +/- 14.5 degrees (SE) at 0.32 Hz. The differences in the dynamic properties of these VS neurons projecting to the lumbosacral cord, with respect to those of previously recorded populations of VS neurons, are discussed. PMID- 8488087 TI - Intracellular ADP activates ATP-sensitive K+ channels in vascular smooth muscle cells of the guinea pig portal vein. AB - Vasodilatation following tissue ischemia is assumed to partially result from activation of ATP-dependent K+ channels (KATP). To assess the effect of cytosolic adenosine nucleotides, the balance of which depends on tissue pO2, on KATP, we have measured steady state outward currents (SSC) by the whole-cell clamp technique in smooth muscle cells of the guinea pig portal vein at different concentrations of ATP and ADP in the pipette solution. Glibenclamide, a selective inhibitor of KATP, was used as a pharmacological tool. With no nucleotides in the pipette solution (Ca(2+)-free), the SSC determined at +20 mV was unaffected by glibenclamide, while with 0.1 mM ATP or with 0.1 mM ADP, the SSC exhibited a glibenclamide-sensitive component indicating activation of KATP. At 5 mM ATP and no ADP, hardly any effect of glibenclamide on the SSC was detected, suggesting inhibition of KATP by this high concentration of ATP. With 0.1 mM ADP at 5 mM ATP however, activation of KATP was achieved. At 10(-7) M Ca2+ in the pipette solution, an increased SSC was measured, but the responses to the nucleotides and/or glibenclamide were not modified. These findings suggest that in vivo, ADP may be involved in the regulation of vascular KATP, linking tissue pO2 with vascular tone and tissue perfusion. PMID- 8488088 TI - An estimate of the calcium content of the sarcoplasmic reticulum in rat ventricular myocytes. AB - The aim of this paper was to estimate the Ca content of the sarcoplasmic reticulum (s.r.) and to compare this with the amount of Ca which enters the cell via the calcium current in systole. The s.r. Ca content was measured electrophysiologically in voltage-clamped rat ventricular myocytes. Rapid application of caffeine produced a transient increase of [Ca2+]i which was accompanied by a transient inward Na-Ca exchange current. The integral of this current gives a measure of the Ca2+ pumped out of the cell by Na-Ca exchange. Ni2+ (5 mM) inhibited the current and decreased the rate of fall of [Ca2+]i to 32% of the control suggesting that Na-Ca exchange is responsible for 68% of Ca removal from the cytoplasm following the addition of caffeine. Correcting for the Na-Ca independent Ca removal suggests that the s.r. Ca content is equivalent to about 120 mumol per litre cell. Furthermore we estimate that, during systole, Ca entry into the cell via the sarcolemmal calcium current is equal to about 6% of the Ca content of the s.r. PMID- 8488089 TI - Contractile response of normotensive rat aorta to serum from salt-loaded Sprague Dawley rats. AB - Sprague-Dawley rats were made hypertensive by 6-week dietary salt loading with 8% NaCl in the diet and compared with control rats which had normal feed and water. At the end of this period, the salt-loaded group developed hypertension but the heart rate did not differ significantly from control. Serum taken from salt loaded rats showed enhanced vasoconstrictor effect on normal rat's aorta when compared with controls. This enhanced vasoconstrictor effect was attenuated by adrenergic receptor blockers but not by serotoninergic blockers. Thus salt loading may induce accumulation of vasoactive agents in the blood of rats. PMID- 8488090 TI - Inactivity induces muscle hypertrophy and redistribution of myosin isozymes in chicken anterior latissimus dorsi muscle. AB - Denervation of the anterior latissimus dorsi (ALD) muscle causes transient muscle fibre hypertrophy and leads to an increase of the SM1 myosin isoform. We tested whether the changes that take place after denervation can be attributed to loss of muscle activity which follows denervation. Neuromuscular activity was prevented by blocking the acetylcholine receptors with alpha-bungarotoxin and thereby paralysing the muscle. Following this treatment, we found increased muscle weight and pronounced hypertrophy of muscle fibres. Also, the proportion of SM1 isomyosin was decreased. Due to the multiple innervation of ALD muscle fibres it is possible to paralyze only part of the muscle. When only a region of the muscle was paralysed a local hypertrophy of fibres was detected, and the change from SM1 to SM2 was most pronounced in the area where activity was blocked. Removal of muscle activity resulted in changes similar to those that occurred after denervation. PMID- 8488091 TI - Simultaneous measurements of cytosolic pH and calcium interactions in bovine lactotrophs using optical probes and four-wavelength quantitative video microscopy. AB - The properties of pH and calcium homeostasis have been investigated in single bovine lactotrophs by the use of the fluorescent indicators 2',7' bis(carboxyethyl)-carboxyfluorescein (BCECF) and fura-2 respectively. A method of simultaneous recording from both dyes loaded in the same cell was used. Despite slight crosstalk between the two dyes, physiologically relevant information about the interrelationship between pH and calcium homeostasis was obtained. Three types of interactions were recorded. First, an increase in calcium due to the discharge of intracellular stores by thyrotropin-releasing hormone resulted in no change in cytosolic pH. Secondly, alkalinization by the addition of a weak base, NH4Cl, induced a large transient (around 1000 nM) and a small (a few tens of nanomoles per liter) sustained increase in cytosolic calcium. The former is partly due to release from agonist-sensitive stores. Thirdly, upon the removal of NH4Cl the cytoplasm became acidic, which induced a release of calcium from intracellular stores in some cells. In addition we demonstrate that the recovery from acid load is sensitive to extracellular Na+, suggesting the presence of Na+/H+ exchange mechanisms in bovine lactotrophs. Interestingly we have also found that, at rest, removal of Na+ from the bathing medium results in a decrease in resting [Ca2+]i, paralleled by a reduction in pHi. This suggests a role for Na+/H+ exchange in determining resting [Ca2+]i. PMID- 8488092 TI - Urea derivatives as tools for studying the urea-facilitated transport system. AB - The effects of urea structural analogues on the urea-facilitated diffusion system were examined in human red cell membranes (pink ghosts) and in antidiuretic hormone(ADH)-stimulated frog urinary bladder epithelia. In both tissues, urea permeability (P(urea)) was dramatically but reversibly inhibited by a number of urea analogues, such as 1-(3,4-dichlorophenyl)-2-thiourea (DCPTU). This urea derivative reduced the urea flux in a dose-dependent manner (90% inhibition of P(urea) at 0.5 mM concentration of DCPTU). With the aim of obtaining irreversible markers of red cell and urinary bladder urea transport systems, urea derivatives were modified by addition of an azido residue (N3) and preliminary experiments of photoaffinity labelling were carried out. Two synthetic urea derivatives: 1-(3 azido-4-chlorophenyl)-2-thiourea (ACPTU) and 1-(3-azido-4-chlorophenyl)-3-methyl 2-thiourea (Me-ACPTU) were shown to be very potent inhibitors of P(urea) when used in the absence of light, with IC50 values 60.3 microM and 31.6 microM respectively, as measured in frog urinary bladder. Both these molecules appeared to bind covalently to the urea carrier in both frog urinary bladder and human pink red cell ghosts, when illuminated in the presence of the tissue: the urea flux, which fell to 30-70% of the value obtained in the presence of ADH after inhibitor addition, remained low after the preparation had been illuminated for 30 min and the inhibitor removed. These results provide an interesting approach to the urea carrier analysis, particularly to the urea or urea analogue binding site on the transport protein. PMID- 8488093 TI - Effect of starvation on neutral amino acid transport in isolated small-intestinal cells from guinea pigs. AB - The effects of starvation on neutral amino acid transport were examined in isolated enterocytes. Starvation stimulated L-alanine transport by the Na(+) dependent system A and the Na(+)-independent system L without producing any changes in either the Na(+)-dependent systems ASC or the passive non-mediated uptake. Starvation produces a twofold increase in Vmax of system A without any change in Kt. Starvation produces an increase in Vmax of system L of 1.7 times without any change in Kt. Activation of systems A and L by starvation was reversible with subsequent refeeding. The effects of a series of amino acids on systems A and L were evaluated. A different inhibition pattern was found in starved animals as compared to controls. Starvation increases Na(+)-dependent L alanine uptake and Na(+)-independent cycloleucine uptake by small-intestinal brush-border membrane vesicles. These results suggest that starvation stimulates amino acid transport across the apical plasma membrane of the enterocytes by inducing specific carrier units. PMID- 8488094 TI - Regulatory volume increase after hypertonicity- or vasoactive-intestinal-peptide induced cell-volume decrease in small-intestinal crypts is dependent on Na(+) K(+)-2Cl- cotransport. AB - The volume of intact crypts isolated from guinea-pig small intestine has been measured to assess the capacity of the cells to regulate their volume after hypertonic shock or vasoactive-intestinal-peptide (VIP)-induced shrinkage. Crypts exposed to anisotonic medium initially behave as perfect osmometers. Continued exposure to a hypertonic (400 mosmol/l) medium was followed by regulatory volume increase (RVI), which led to complete volume recovery in about 20 min. VIP produced a volume reduction, attributed to KCl loss through channels activated by the secretagogue, without any recovery during exposure to the polypeptide. Removal of VIP led to an increase of cellular volume towards control levels. This volume recovery after secretagogue-induced shrinkage is termed SVI. Both RVI and SVI were abolished by removal of Na+ or Cl- from the bathing solution, by addition of the loop diuretic bumetanide (1 microM), but not by addition of ethylisopropylamiloride (10 microM) or amiloride (1 mM). Cell shrinkage was also observed when tonicity was increased by addition of 100 mM NaCl or 200 mM D mannitol, but RVI was seen only when NaCl was the added osmolyte. The ion dependence, pharmacological sensitivity and thermodynamic considerations of these effects are consistent with the operation of a Na(+)-K(+)-2Cl- cotransport mechanism activated by cell shrinkage and the secretagogue action of VIP. PMID- 8488095 TI - Relation between regional electrical activation time and subepicardial fiber strain in the canine left ventricle. AB - To determine the relation between regional electrical activation time and fiber strain, epicardial electrical activation and deformation were measured in six open-chest dogs at the left ventricular anterior free wall after 15 min of right atrial, left ventricular free wall, left ventricular apex, or right ventricular outflow tract pacing, when end-diastolic pressure was normal or elevated (volume loading). Regional electrical activation was measured using a 192-electrode brush. Regional subepicardial fiber strain (ef) was measured simultaneously in 16 regions, using optical markers which were attached to the epicardial surface and recorded on video. When relating regional ef during the ejection phase to regional activation time, the best correlation was found when a hemodynamic time reference rather than an electrophysiological one is used. Using the moment of the maximum rate of change of left ventricular pressure as the time reference for electrical activation, regional electrical activation time (t(ea)) and the degree of ef during the ejection phase could be fitted by a linear regression equation ef = a t(ea) + b, in which a = -3.46 +/- 0.73 s-1 an b = -0.28 +/- 0.05. For electrical activation times ranging from -40 to -80 ms, fiber strain was estimated with an accuracy of +/- 0.026 (+/- SE) with this relation. During right atrial pacing, t(ea) and ef were on the average -48 ms and -0.10 respectively. On further investigation, the relation between ef and t(ea) appeared to be influenced by end-diastolic pressure. For normal (1.1 kPa) and elevated end diastolic pressure (1.8 kPa), the slope of the linear regression line was -3.96 and -2.86 s-1, respectively. Three conclusions may be drawn. Firstly, the time interval between the moment of regional electrical activation and the moment of the maximum rate of change of left ventricular pressure is an index of regional fiber strain. Secondly, it can be concluded from the above equations that electrical asynchrony of more than 30 ms causes non-uniformities in the degree of ef of the order of mean ef during pacing from the right atrium. Finally, differences in fiber strain during asynchronous electrical activation are less pronounced at larger filling pressures. PMID- 8488097 TI - [Cerebral MR imaging in patients with primary biliary cirrhosis]. AB - Five patients with primary biliary cirrhosis (PBC) underwent cerebral magnetic resonance (MR) imaging to evaluate subclinical hepatocerebral degeneration. All patients were neurologically asymptomatic, but three of the five patients had symptoms such as jaundice and itching. Symmetrically hyperintense globus pallidi were observed on T1-weighted images in four of the five patients. One remaining patient who had normal MR images was an asymptomatic fresh case. Patients with markedly hyperintense globus pallidi also had mildly increased signal intensities in the surrounding structures. On proton-density- and T2-weighted images, there were no abnormal signals in the globus pallidi any of the patients. Portal systemic collateral vessels were demonstrated in three of the four patients with abnormal MR images. The mechanisms by which T1-shortening of the globus pallidi occurs remains obscure. We believe that both portal-systemic collaterals and cholestasis play a prominent role in the cause of cerebral abnormalities on T1 weighted images. PMID- 8488096 TI - Small-conductance Ca(2+)-activated K+ channels in bovine chromaffin cells. AB - Simultaneous whole-cell patch-clamp and fura-2 fluorescence [Ca2+]i measurements were used to characterize Ca(2+)-activated K+ currents in cultured bovine chromaffin cells. Extracellular application of histamine (10 microM) induced a rise of [Ca2+]i concomitantly with an outward current at holding potentials positive to -80 mV. The activation of the current reflected an increase in conductance, which did not depend on membrane potential in the range -80 mV to 40 mV. Increasing the extracellular K+ concentration to 20 mM at the holding potential of -78 mV was associated with inwardly directed currents during the [Ca2+]i elevations induced either by histamine (10 microM) or short voltage-clamp depolarizations. The current reversal potential was close to the K+ equilibrium potential, being a function of external K+ concentration. Current fluctuation analysis suggested a unit conductance of 3-5 pS for the channel that underlies this K+ current. The current could be blocked by apamin (1 microM). Whole-cell current-clamp recordings showed that histamine (10 microM) application caused a transient hyperpolarization, which evolved in parallel with the [Ca2+]i changes. It is proposed that a small-conductance Ca(2+)-activated K+ channel is present in the membrane of bovine chromaffin cells and may be involved in regulating catecholamine secretion by the adrenal glands of various species. PMID- 8488098 TI - [CT finding of right diaphragmatic rupture due to blunt trauma--subhepatic hemothorax]. AB - Owing to the poor detectability of the anatomic location of diaphragm on the parallel plane of computed tomography (CT), capability of CT to predict traumatic ruptured diaphragm has been debated in several reports. A specific hematoma (subhepatic hemothorax) adjacent to the posterior attachment of the right diaphragm was identified on CT. The finding originated from herniated liver that migrated to the posterior thoracic wall as a result of gravity, to separate the hemothorax in the supine position. This was surgically proven in two patients after blunt traumatic accident. The finding is useful in predicting right diaphragmatic rupture on CT study. The formation of subhepatic hemothorax, its differential diagnosis and a brief review of diaphragmatic rupture are discussed. PMID- 8488099 TI - [Clinical utility of Gd-DTPA subtraction MR imaging for spinal bone metastasis]. AB - Based on reports that Gd-DTPA contributes to the detection of tumors, we used it in 31 cases (97 lesions) of spinal bone metastases. The result was that Gd-DTPA increased the intensity of tumors and the surrounding bone marrow to almost the same level in 53%. To show the metastases clearly, an existing subtraction command system was utilized. The technique included the pixel-by-pixel method, to obtain a Gd-DTPA T1-weighted image (T1WI) subtracted by the original T1WI. The detectability of the subtraction image was improved up to 96%, but was less than the original T1WI (99%). Because of the different imaging rationale between two methods, a means to assess the quality of diagnosis must be proposed. To check the normal background, the same kind of postprocessing was performed in 21 patients without malignancy. Gd-DTPA perfusion was highest in the paravertebral veins, moderate in muscles and epidural fat, and lowest in the spinal cord, intervertebral disk and bone cortex. Gd-DTPA enhanced subtraction MR imaging provides a new diagnostic tool to detect and to assess bone metastasis. PMID- 8488100 TI - [MR tractography--visualization of structure of nerve fiber system from diffusion weighted images with maximum intensity projection method]. AB - We developed a new noninvasive technique to visualize the anatomical structure of the nerve fiber system in vivo, and named this technique magnetic resonance (MR) tractography and the acquired image an MR tractogram. MR tractography has two steps. One is to obtain diffusion-weighted images sensitized along axes appropriate for depicting the intended nerve fibers with anisotropic water diffusion MR imaging. The other is to extract the anatomical structure of the nerve fiber system from a series of diffusion-weighted images by the maximum intensity projection method. To examine the clinical usefulness of the proposed technique, many contiguous, thin (3 mm) coronal two-dimensional sections of the brain were acquired sequentially in normal volunteers and selected patients with paralyses, on a 1.5 Tesla MR system (Signa, GE) with an ECG-gated Stejskal-Tanner pulse sequence. The structure of the nerve fiber system of normal volunteers was almost the same as the anatomy. The tractograms of patients with paralyses clearly showed the degeneration of nerve fibers and were correlated with clinical symptoms. MR tractography showed great promise for the study of neuroanatomy and neuroradiology. PMID- 8488101 TI - [Clinical usefulness of helical scanning CT (HES-CT) for orbital lesion]. AB - Helical scanning CT (HES-CT) was applied to multiplanar reconstruction (MPR) and 3-D imaging for the diagnosis of 65 patients with orbital lesions. We employed the the Toshiba TCT-900S, a fourth-generation high-speed CT scanner equipped with a slip-ring system. In HES-CT, scanning was performed with continuous rotation of the X-ray tube for 30 s, while the couch top was simultaneously moved at a constant speed of 1 to 2 mm/s. Images were reconstructed from continuous raw data to obtain a slice pitch of 1 mm in the longitudinal direction. HES-CT was found to have some advantages over conventional thin slice CT: 1) a wide area could be scanned in a short time (30 s) without motion artifact, 2) small lesions could be easily detected because slice images could be generated with a fine pitch at arbitrary positions from continuous raw data, 3) MPR images had good continuity in the longitudinal direction, and 4) high contrast of structures was obtained in the orbital region. HES-CT was considered to be useful for the detection of orbital lesions. PMID- 8488102 TI - [MR imaging of pituitary dwarfism]. AB - Pituitary MR imaging was performed in 32 patients with clinically diagnosed pituitary dwarfism and 12 normal controls. The patients were divided into two groups according to the severity of pituitary dwarfism based on endocrinological data. The two patients with severe dwarfism showed transection of the pituitary stalk, ectopic posterior lobe and atrophy of the anterior lobe on MR imaging, while the 27 patients with mild dwarfism showed no abnormal MR findings of the pituitary gland. The former group corresponds to typical pituitary dwarfism and the latter to partial GH deficiency, which was recently proposed as another type of pituitary dwarfism. In conclusion, pituitary MR imaging may differentiate partial GH deficiency from typical (stalk-transected) pituitary dwarfism. PMID- 8488103 TI - [Efficacy of ultrasound detection of the oro- and hypopharyngeal carcinoma]. AB - Sixteen histologically confirmed carcinomas of oro- and hypopharynx were examined by ultrasonography (US) from submental, submandibular, sub-auricular, and laterally cervical skin surface. Well-circumscribed hypoechoic tumors were demonstrated in twelve cases (75%). Nine of them had partial hypoechoic areas, such as "bull's eye pattern" or "pseudokidney sign". The remainder were one homogeneous hypoechoic mass and two inhomogeneous bulky tumors. In four negative studies, two were suspected too thin to be detected by US, and the other two could not be visualized by percutaneous scan because of their anatomical sites. The dimensions of demonstrated twelve tumors were measured three-dimensionally. The US information should be valuable for a prediction or an evaluation of the radiotherapy efficacy. PMID- 8488104 TI - [Radiation stenosis and fistula formation developed after iridium-192 high-dose rate intracavitary radiation boost therapy for carcinoma of the esophagus]. AB - Intracavitary irradiation using a high-dose-rate Ir-192 remote after-loading system was applied to 14 advanced or inoperable patients with esophageal carcinoma as a boost therapy. The total dose of external irradiation was 45-70 Gy/15-35 fractions and that of intracavitary irradiation was 11.6-34.0 Gy/2-4 fractions at a point 5 mm deep from the inner surface of the esophageal mucosa. The time-dose-fractionation factor (TDF) of the whole treatment was 116-186 (mean, 146). Six patients (43%) had complete response (CR), three (21%) had partial response and five (36%) had no response. Esophageal carcinoma that showed exophytic growth, was less than 5 cm ling, and showed favorable response to external irradiation was likely to be a good candidate for intracavitary radiation boost therapy. Fistula formation was produced in five patients (36%), four of whom were irradiated at more than 140 TDF. All six CR patients were free from esophageal tumors, but severe esophageal stenosis due to radiation injury developed in five (83%) of them. They were irradiated at more than 135 TDF. One- and two-year survival rates were 28.6% and 14.3%, respectively. The poor prognosis was ascribed to the frequent occurrence of fatal radiation stenosis and fistula formation. An appropriate therapeutic dose for esophageal carcinoma that does not cause severe radiation stenosis was estimated to be under 120 TDF. PMID- 8488105 TI - [A case of alcoholic liver cirrhosis associated with portal vein thrombosis which was successfully treated by TIPS]. AB - We reported a case of 51-year-old man with repeated bleeding from gastroesophageal varices and portal vein thrombosis which were successfully treated by transjugular intrahepatic portosystemic shunt (TIPS) and thrombolysis. We used a flexible tip puncture needle (.038") which was thought to be safer than Colapinto needle (16G). PMID- 8488106 TI - [Magnetization transfer contrast imaging of the skeletal muscle in gradient recalled echo sequence]. AB - The human midcalf muscle images were obtained using gradient recalled echo (GRE) sequence with and without magnetization transfer contrast (MTC) sequence. A significant decrease of relative signal intensity was observed in muscle with off resonance irradiation. The percentage increase of signal intensity after dorsiflexion exercises was 55.6% and 29.0% for MTC-GRE and GRE sequence, respectively. MTC technique might be useful in improving contrast between many tissues as well as muscles. PMID- 8488107 TI - [Evaluation of early MR imaging of the liver in rabbits after ethanol injection]. AB - Seven days after ethanol injection, MR images of the liver in 5 rabbits were evaluated by T1, T2-weighted SE and TURBO-FLASH dynamic images. Necrotic area was visualized as low-intensity on T1-weighted images and high-intensity on T2 weighted images. These findings were similar to the tumor that was not treated, so it is necessary to be careful for evaluation of therapeutic efficacy. Necrotic area was not meanwhile enhanced on TURBO-FLASH dynamic images, therefore, dynamic study seemed to be useful for therapeutic efficacy after ethanol injection. PMID- 8488108 TI - [Embolization of the internal maxillary artery for severe epistaxis--including an experience of the approach from the superficial temporal artery]. AB - Six cases of severe epistaxis were treated with the super-selective intraarterial embolization of the internal maxillary artery. Tens of fragments of Gelfoam were delivered into the distal internal maxillary artery and, additionally, embolized by several pieces of the coils. In a case with cerebral infraction, catheter was inserted via the superficial temporal artery. There were no complications due to these procedures in all cases of this study. It is considered that therapeutic intraarterial embolization of the internal maxillary artery is an effective therapy for severe epistaxis and the superficial temporal artery approach is useful for selected cases. PMID- 8488109 TI - Risk: a concept worthy of attention. AB - Clients often engage in behavior that involves risk. Consequences of this behavior are sometimes harmful, but not always. Many times clients' views of the risks they are taking are often based on personal decisions they have made about their own health. People who take risks are frequently quite knowledgeable. The author uses case studies to examine the concept of risk. The author posits that teaching plans must account for the risks that clients take. Teaching plans should reflect that risks/benefits need to be discussed. Teaching should reflect respect for patient choices. An open discussion with the client that reflects what is really happening in the client's everyday life is of far more value than scanty, often glossed-over reports clients are accustomed to giving health professionals. PMID- 8488110 TI - Are there employment risks to ethical decisions? AB - A 1991 Washington State Supreme Court decision revisited the issue of job protection for a nurse who criticizes her employer for a treatment policy or practice that, while apparently legal, she believes to be unethical. In a case involving artificial nutrition and hydration, the court held that a nurse who tried to change her nursing home employer's policy of permitting withdrawal was acting to promote her own values, not the public good, and therefore was not entitled to protection by the public policy exception to the employment-at-will doctrine. PMID- 8488111 TI - Counseling implications in a client's choice of anesthesia during a first or repeat abortion. AB - Deciding to have an abortion is a process that causes most women a great deal of distress. This study addresses the question of whether a difference exists in psychological distress between women having abortions under local and general anesthesia. A two-factor analysis of variance design was utilized. The level of psychological distress among four groups of women was measured: Those experiencing a first-time and a repeat abortion under local anesthesia and those experiencing a first-time and repeat abortion under general anesthesia. A main effect for anesthesia was found for the variables of somatization, depression, hostility, psychotocism, global severity index, and positive symptom total. Specifically, women experiencing abortions under general anesthesia experienced more psychological distress in the above variables. Data suggest an association between psychological distress concerning the procedure and choice of anesthetic method may provide clues to the women's counseling needs. PMID- 8488113 TI - Seeking one's sacred space. PMID- 8488112 TI - Nursing: a scientific discipline? 1972. PMID- 8488114 TI - The challenge of accountability in nursing. AB - The authors examine the literature on accountability in nursing and analyze the following questions: What is meant by accountability in nursing? To whom are nurses accountable? For what should nurses be held accountable? Finally, the implications of accountability for the nursing profession are explored. In order for nursing to grow and develop as a profession based on sound theoretical foundations, nurses need to examine what it means to be truly accountable. The authors point out that accountability is a complex issue that requires nurses to examine their practice relative to the needs of healthcare consumers, their relationships with other healthcare professional, and the increasingly critical role of nursing in the healthcare system. PMID- 8488115 TI - Failure of one conductor in a nonthoracotomy implantable defibrillator lead causing inappropriate sensing and potentially ineffective shock delivery. AB - We describe how a single defect in a new model transvenous lead for an implantable cardioverter defibrillator can result in malfunction of the sensing and defibrillation circuits. The patient had received shocks during atrial fibrillation without premonitory symptoms. At least one shock was delivered and not felt by the patient. In addition, late in the course, a shock was delivered during atrial fibrillation documented to be with a slow ventricular response. In the transvenous lead, a distal spring functions as the anode for rate sensing and the cathode for defibrillation. The wire from this spring bifurcates near the proximal end of the catheter. One wire from the bifurcation leads to the positive (anode) rate-sensing socket of the pulse generator, and the other wire leads to the negative (cathode) high voltage output socket of the defibrillator for defibrillation and cardioversion. After the inappropriate and unperceived shocks were documented, intraoperative and postoperative electrical testing indicated that intermittent discontinuity of the distal spring system within the proximal yoke of the catheter caused faulty sensing and potentially unreliable defibrillation. This dual malfunction was possible because the distal spring of the lead functions in the high-voltage output and the rate-sensing low-voltage input circuits of the implantable defibrillator. PMID- 8488116 TI - [Reduced natural killer function in children with recurrent respiratory tract infections]. AB - Respiratory infections are the major cause of disease in childhood in the industrialized areas of the world. This essentially depends on two factors: immunological immaturity and immunological naivety. In most cases a virus has been considered the causative agent in respiratory infection. A defect in immune responses has been described in children with recurrent respiratory infections and in particular a decrease in CD4/CD8 T lymphocyte ratio or in IL-2 and IFN gamma production. Our results show that Natural Killer (NK) cell activity is defective in children with recurrent respiratory infections. That is particularly noteworthy since NK cells play an important role in host defense against viral infections. At present it is difficult to understand whether the NK defect is a primary defect or it is secondary to viral infections. Further studies will help to clarify whether NK decreased activity depends on a cell damage directly caused by virus or it depends on the decreased levels of cytokines. PMID- 8488117 TI - [Hemangiopericytoma in childhood: presentation of an unusual clinical case]. AB - A case of retroperitoneal Hemangiopericytoma in a 9 year old boy is presented. Hemangiopericytoma is a rare soft tissue tumor with unpredictable biological behaviour and a high local recurrency rate. Its ubiquity, the different grades of malignancy, the lack of correlation between clinical and histological feature are discussed. It is emphasized the hard preoperative diagnosis of the painless "mass", that can be reached only by histology. Increased cellularity, prominent mitotic activity, and foci of necrosis or hemorrhage suggest a malignant form rather than a benign one. Classifying Hemangiopericytoma among mesenchymal tumors, radical surgery is the treatment of choice whenever possible, associated with pre or post operative chemotherapy according to National Protocol RMS 88. PMID- 8488118 TI - [Gastroesophageal reflux and respiratory pathology]. AB - The prevalence of gastroesophageal reflux (GER) in 86 children with respiratory disease (recurrent pneumonia, chronic cough, bronchial asthma) has been evaluated by mean of prolonged (22-24 hours) esophageal pH-monitoring. The following parameters were evaluated: the total percentage of time pH < 4 and the percent time the esophageal pH was < 4 while sleeping. None of the children had gastrointestinal symptoms suggesting GER and no neurological disorder was noted in any of the studied patients. The mean age was 68.98 +/- 46.46 months (range 14 189); 53 (61.6%) males and 33 (38.4%) females were considered in the study. Atopy was evidenced in 42/86 (48.8%) children (total IgE > 2SD in 42/86 and prick tests positiveness in 32/86. A pH-metry indicating pathological GER was present in 52/86 (60.5%) children: 39/62 (62.9%) patients with bronchial asthma, 5/10 (50%) subjects with chronic cough and 8/14 (57.2%) children with recurrent pneumonia. No significant difference in the diagnosis of GER was recorded between atopic or non-atopic patients. The children with abnormal pH-metric recording were also evaluated by upper gastrointestinal series and/or endoscopy. A conventional barium radiology was performed in 44/52 patients and confirmed GER in 19/44 (43.2%). Esophagitis was evidenced in 21/46 (45.7%) studied patients. The presence of esophagitis was significantly (p = 0.032) related to the total percentage of time pH < 4, but the most significant (p = 0.002) association was with the percent time the esophageal pH was < 4 during sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488119 TI - [Multiple pterygium syndrome: description of a new clinical case]. AB - Multiple Pterygium Syndrome is a rare autosomal recessive disorder characterized by short stature, multiple pterygium, joint contractures, vertebral fusions and minor facial anomalies. Due to the extreme phenotypic variability of this syndrome many mild cases may be misdiagnosed or not recognized. The importance of an early diagnosis is to provide an adequate follow-up of these children in order to try to prevent many of the clinical problems they may encounter in their life time. PMID- 8488120 TI - [IgG subclasses against bovine alpha-lactalbumin and beta-lactoglobulin in infants fed with a seroprotein hydrolysate]. AB - Prevention of food allergy in infancy has been the aim of important researches in the last years but many studies have produced conflicting conclusions. The use of hydrolysate formulas seems to be an helpful tool in prevention of cow milk protein allergy but confusion often remains about capability of small hydrolysate molecules to be "allergens" or "antigens". In order to clarify this point IgE, IgG and IgM as well as IgG subclasses against alfa-lactoalbumin (ALA) and beta lactoglobulin (BLG) have been evaluated in 41 infants at risk for allergy and in 30 controls at the fourth month. The same evaluation has been done on their mothers. The 41 "at risk" children were fed with breast milk or with an hypoallergenic formula (Nidina HA, Nestle) or both. The control children received an adapted formula. No difference between the two groups of children was found regarding IgM or IgG against ALA while antibodies against BLG were more frequently found in controls than in "at risk" children. Only one child in the group fed with Nidina HA developed specific IgE against whole milk. Therefore hydrolysate formula seems to be as antigenic (not allergenic) as adapted formula in respect of ALA while BLG contained in adapted formula seems to be a stronger immunogen. The pattern of specific IgG subclasses against ALA and BLG is different between the two groups of children because of the absence in "at risk" group of specific IgG2 and IgG3. As for the mothers, the presence in their sera of IgG against ALA or BLG seems to induce in infants a reduced response to the same antigen. PMID- 8488121 TI - [Screening of urologic pathology in newborns with prenatal and postnatal echography]. AB - We compared the results, by prenatal ultrasonography, effected on 2592 foetus at the 15th-25th-35th weeks of gestation with the ones, made by postnatal ultrasonography, effected the 5th day of life on 2539 infants born from pregnancies previously monitored. We considered the obstructive and not obstructive malformations. The prenatal ultrasonography put in evidence 19 cases of urological pathology, which is 0.75%. The postnatal research established the truth of 14 cases, which is 0.55%; 7 cases underwent a precocious surgical operation. Percentage of positive false is 0.2%. The postnatal ultrasonography made evident 30 cases which can be considered pathological: 25 uropathy obstructive cases and 5 uropathy not-obstructive cases; 3 of them underwent precocious surgical operation. The result is 44 pathological cases (1.74% of infants). We also considered an heterogeneous group of non-nephro-urological anomalies (0.47%), a casual medical report of this research; in particular, 10 cases of surrenal hematoma and 1 case of neuroblastoma. The Authors remark that it's useful to complete the prenatal ultrasonographic research with another postnatal ultrasonographic research, particularly in the nephro-urological pathology; and they hope this system can be much more diffuse. PMID- 8488122 TI - [Urinary tract infections in newborns: sensitivity, specificity, and predictive value of urinary screening with the reagent strip test]. AB - Important considerations in evaluating newborn urine examinations by dip-stick method are: ease of performance, the volume of the specimen required for test, the time required to perform the test and the cost. In considering the dip-stick test for the early diagnosis of Urinary Tract Infections (U.T.I.), it has never been tested with later follow-up to evaluate its sensitivity and specificity, also in regard to reduce the risk of further complications for urinary tract and kidney. PMID- 8488123 TI - [Epidemiologic correlation between microhematuria in children and hypertension in their parents]. AB - The significance of asymptomatic microhematuria in children is unknown. In 1976 Dodge et al. found a "surprising" high prevalence of proteinuria and haematuria in 12,000 healthy schoolchildren and, in the absence of knowledge of the natural history, this finding prompted them to postpone urinary mass screening. Nonetheless, the progressive course of most chronic renal disease in adulthood argues for investigation of microhematuria in children to uncover any sub-groups "at risk" of kidney diseases. The sensitivity of screening for microhematuria could be increased by a questionnaire on family medical history? We have investigated 1554 boys and 1484 girls aged 3-12 years, from the school population of a rural district near Rome. A self-administered questionnaire on renal disease and related symptoms in families was distributed to the parents. Urinalyses were done on all the children except for those with diseases or symptoms related to the urinary apparatus and girls who were menstruating. Haematuria was tested for by dipstick ("Combur 7"; Boehringer), children with microhematuria were retested 10 day and 1 year later. On the initial 3038 dipstick tests 175 (5.76%) were positive, and 52 children (1.71%) had haematuria in all three specimens. The questionnaires were used only if they had been filled in properly (1821/3038). Of the 1821 valid questionnaires 121 (6.64%) revealed a family history of hypertension, but the frequency of such a family history was significantly higher for the 128 children with haematuria (14.8%, p < 0.005) and the 52 with persistent haematuria (23.0%; p < 0.001). PMID- 8488124 TI - [Echo-Doppler, exercise test, NMR in the follow-up of surgically treated aortic coarctation]. AB - Persistent hypertension is one of the causes of sudden death which sometimes happens in patients operated on for coarctation of the aorta. Seven patients operated on for coarctation of the aorta were examined using exercise testing (Treadmill-Bruce), Echo-Doppler and NMR. Pressure gradients between the right upper and lower limbs were compared with those of normal young people and evaluated using NMR. The authors conclude that the patients operated on have resting blood pressure and pressure gradients, both resting and during exercise, greater than normal. Some patients operated on, with normal resting blood pressure and a slight gradient, can develop hypertension during exercise and a significant pressure gradient. Significant gradients during exercise are correlated to isthmic obstruction which is visible on the NMR. Follow-up after surgical repair of coarctation of the aorta cannot exclude measurement of exercise pressure gradients. This gives more physiological information compared with pressure gradients measured at rest. PMID- 8488125 TI - [Antibodies against milk and soy proteins in specific intolerances and celiac disease]. AB - It has been suggested that high serum level of food proteins antibodies (especially cow's milk protein antibodies) may have a specific meaning in the diagnosis of food allergy, especially presenting with gastrointestinal complaints. In our study we tested with enzyme-linked immunoabsorbent assay test (ELISA) the antibody serum level to cow's milk and soy proteins in 123 children. The following patients were included in the study: 30 children with cow's milk enteropathy (CME), 27 children with soy proteins intolerance (SI), 19 coeliac children on gluten containing diet (CD), 9 coeliac children on gluten free diet (GFD) and 50 healthy sex and age matched control children. All coeliac patients had assumed cow's milk and soy proteins at the moment of the test or a few days before. Higher antibody serum level was found in coeliac disease to both cow's milk and soy proteins and in cases with cow's and soy allergy, than in control cases. The highest mean value of cow's milk and soy proteins antibodies have been found in the untreated coeliac children (CD), also higher than in the two groups of specific allergy. In treated coeliac children (GFD) with normalized jejunal mucosa cow's milk and soy proteins antibodies was normal. None of the 19 CD with high cow's milk and soy proteins antibodies level showed clinical intolerance to cow's milk and soy proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488127 TI - [Cholestasis associated with sepsis in newborns]. AB - Cholestatic jaundice is a well-known complication of gram-negative bacterial infections in the neonates. Newborn and premature infants are particularly vulnerable to cholestasis because of immaturities in bile forming mechanisms. The Authors describe two premature infants who developed cholestasis in the course of a proved bacterial infection by Klebsiella pneumoniae. The main clinical aspects of this association are illustrated and the recent concepts of pathogenetic mechanism of intrahepatic cholestasis is discussed. PMID- 8488126 TI - [Hepatitis B virus: new markers and their immunology]. AB - Hepatitis B virus (HBV) is one of the most important causes of chronic liver disease. HBV is a DNA virus with an external glycoprotein surface and an internal nucleocapsid which contains the viral genome. HBV infection is revealed by the appearance of specific markers. Some of these markers are well known and their presence in serum is important to understand the behaviour of the disease. Among them HBsAg, HBeAg, anti-HBs and anti-HBe are found in serum, so as anti-Core; the HBcAg may be found in hepatic tissue and marks infectivity and virus replication. In the few last years some new antigens and antibodies have been studied and their importance in diagnosis and follow-up of hepatitis has been recognized. HBxAg, Pre-S and DNA-Polymerase (Pol) seem to be specific and early signals of viral replication. More studies showed the trans-activating properties of HBxAg; actually the X protein seems to be involved in replicative cycle of HBV. Many Authors also demonstrated a relationship between the presence of X in serum and/or liver and the progression of disease to cirrhosis and hepatocellular carcinoma. The Pol antigen and its antibody seem to be very common markers of HBV infection in serum of patients with hepatitis. Moreover their presence is the only signal of viral infection in some patients which have no other marker of HBV. More studies are of course needed to exactly establish the significance of these new markers and their importance for diagnosis and prognosis of HBV infection. PMID- 8488128 TI - [Migraine and food intolerance: a controlled study in pediatric patients]. AB - The possible correlation between migraine and food intolerance has been found to be of great interest in the recent literature. We have studied 43 patients aged from 7 to 18 years suffering from migraine without aura according to the classification of International Headache Society (IHS): they had at least 2 attacks monthly and they were pharmacological free of any prophylactic treatment for the latest three months. Each patient was given an allergologic anamnesis. Half of them (group A) were first in oligoantigenic regimen (including 8 simple foods) for 4 weeks. Afterward each patient has been challenged weekly in an open trial, introducing in the diet the different foods and additives previously eliminated; then they have been controlled in a simple double blind study. We have taken skin tests (PRICK method) for the most important allergens (foods and main inhalants), plasma levels of total and specific IgE (PRIST and RAST method), and moreover we have taken histamine plasma levels at the beginning and at the end of the oligoantigenic diet, and during challenge test, only in case of headache attacks. The second half of the patients (group B) were not following any diet nor a pharmacological prophylaxis, but they have been followed up with a clinical diary. Among the patients on oligoantigenic diet 12 only concluded the trial: 6/12 presented a completed remission of headache, 5/12 had a significant improvement of the migrainous pattern, 1/12 patients did not get any improvement after the dietetic treatment. The food recognized responsible of the attacks were: cacao, banana, egg, hazelnuts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488129 TI - [Non-ketotic hypoglycemia caused by carnitine palmitoyl transferase 1 deficiency]. AB - A 9-year-old girl was referred to our hospital after recurrent episodes of hypoglycemia, altered consciousness and persistent vomiting without acetonemia or myopathic symptoms. Other pertinent laboratory data included elevated BUN, hyperammonemia and very low levels of triglycerides with elevated free fatty acids. The patient was born from unaffected but related parents (second cousins) and the illness was previously diagnosed as Reye encephalopathy. Recurrence of similar attacks suggested an underlying metabolic disorder. Several syndromes of impaired FFA beta oxidation were taken into account and discarded successively after laboratory investigations: systemic carnitine deficiency, Medium and Long Chain Acyl-CoA Dehydrogenase deficiency and Multiple Acyl CoA Dehydrogenation deficiency (Glutaric aciduria, Ethylmalonic-adipic aciduria and riboflavin responsive multiple acyl CoA dehydrogenation deficiency). Urinary and hematic gas chromatography and Mass-Spectrometry show no abnormality in Medium Chain fatty acids and in C6-C10 dicarboxylic acids. Carnitine plasma concentrations (both total and free) were above normal levels while in urine acetyl carnitine was low in respect to longer acyclic radicals. Among metabolic defects located at the level of hepatic fatty acid oxidation, only Carnitine Transferase deficiency can explain this peculiar mosaic of data (precursors of the blocked reaction are elevated in blood whereas lack of the metabolites derived uniquely from this reaction explains all the clinical manifestations). PMID- 8488130 TI - [Acute scrotum in childhood: considerations on 457 cases]. AB - The Authors present their experience about 457 consecutive cases of acute scrotum, occurring from 1980 to 1990, at their Pediatric Surgery Unit. The condition is caused by torsion of the appendage of the testis (78.1%), torsion of the funicle (9.6%), acute idiopathic oedema of the scrotum (2.87%), and also tumours (1.17%). Also in their experience, the surgical approach is the correct treatment for the acute scrotum in order to prevent the irreversible damage of the testis. The surgical treatment present no problem and all the post-operatives were uneventful. In children under 2 years, the interventions were performed by inguinal incision, above 2 years by scrotal incision. The contralateral orchiopexy, in case of torsion of the funicle, was performed in the same session, or performed later, because of the anesthetic consideration. PMID- 8488131 TI - [Primary Toni-Debre-Fanconi syndrome]. AB - A case of primary de Toni-Debre-Fanconi syndrome with hypercalciuria and urinary calculosis was reported and the relationships between congenital and acquired de Toni-Debre-Fanconi syndrome are discussed. The dysmorphic, facial features of primary de Toni-Debre-Fanconi are particularly outlined and common, genetic basis supposed. The new studies about the tubular defect for aminoaciduria, phosphaturia and glycosuria are reported and discussed. For the de Toni-Debre Fanconi syndrome primary and on genetic basis, the name "de Toni-Debre-Fanconi disease" is appropriate. PMID- 8488132 TI - [Xanthogranulomatous pyelonephritis in childhood: considerations on 2 new cases]. AB - The Authors report their experience about two cases of xanthogranulomatous pyelonephritis in childhood. The clinical history, diagnostic procedures and surgical treatment are described. The xanthogranulomatous pyelonephritis is a rare form of chronic inflammatory disease of the kidney, in which pre-operative differential diagnosis with renal cancer or with extra renal neoplastic and inflammatory diseases is very difficult. The signs and symptoms are not characteristic, such as renal tumour, recurrent UTI, abdominal pain, fever. Also non characteristic are the findings, performed with diagnostic ultra sound and computed tomography. The surgical treatment is always effective in the xanthogranulomatous pyelonephritis. About 500 cases are described in adults and about 80 cases in children, from the first description in 1963. The first of our cases, occurring in a boy 6 years old, was treated with nephrectomy, because of the pre-operatory aspect was like tumour. In the second of the cases described, occurring in a girl 11 years old, the nephrectomy was performed because the chronic purulent inflammatory process had involved all the kidney. In the post operative, in the first case was performed a relaparotomy for intestinal occlusion in 12th day, in the second case the post-operative was uneventful. The Authors emphasize the importance of the xanthogranulomatous pyelonephritis in the differential diagnosis in children with recurrent UTI, renal masses, fever, in the clinical history. PMID- 8488133 TI - [Kawasaki disease in Sicily: description of the first case with giant coronary aneurysm]. AB - A case of Kawasaki disease with early development of giant coronary artery aneurysm is reported. The delay in the diagnosis and consequently in the use of correct therapy has conditioned the outcome of the illness. We don't know the predictive factors of cardiac complications, but steroid treatment in our patient probably had an important role in the cardiac damage. The use of echocardiography in the evaluation of coronary aneurysm has confirmed the sensitivity, specificity and predictive value of this technique in detecting cardiac lesions. PMID- 8488134 TI - [Respiratory function involvement in intestinal chronic inflammatory disease: description of a case]. AB - In the process of chronic intestinal inflammatory diseases the involvement of other organs and apparatuses is frequent. The respiratory apparatus, however, is not so frequently concerned as other organs, especially with regard to the paediatric age. The rarity of clinical evidences concerning the respiratory apparatus contrasts with the anomalies of the lung functionality tests described in literature. A fifteen year old boy is taken into consideration. He was first examined at the age of nine, when his symptomatology (slight fever and abdominal pain) was regarded as a chronic intestine inflammatory disease and it was treated with salazopyrina and cortisone. Compilations supervened later on, such as ilium arthritis, psoriasis-like dermatitis, perineal abscess. Five years after the beginning of the intestine disease the lungs were also involved and there was evidence of dyspnoea, especially when the patient was under stress. The clinical picture was confirmed by the reduction of the parameters of the respiratory functionality in the sense of an insufficiency of obstructive and restrictive kind. The pulmonary compilation was treated with disodium cromoglycate; such treatment was stopped, after the appearance of headache. After more than a year since the supervening of the lung complication the patient is being kept under periodic control to evaluate his pulmonary functionality. The indexes are constantly altered in the sense of a reduction of FEV 1, of FVC, of FEF 25-75 and of PEF, while the ventilatory and perfusional pulmonary scintigraphy has not shown relevant anomalies. PMID- 8488135 TI - [Juvenile fibromyalgia syndrome: 2 clinical cases]. AB - We report two cases (F. 11 years, M. 7 years) with juvenile fibro-myalgic syndrome, diagnosed because of the presence of musculo-skeletal pain, tender points and associated symptoms, and after exclusion of any other known etiology. Both patients improved after treatment with antidepressant serotoninergic (amitriptyline, trazodone). PMID- 8488136 TI - Missed appendicitis in a pediatric emergency department. AB - Appendicitis is the most common cause of abdominal pain requiring surgery in children. Missed appendicitis is also a frequent cause of professional liability in an emergency department (ED). A retrospective review of all patients with appendicitis diagnosed in the ED was undertaken to identify: 1) how many patients required more than one visit to diagnose appendicitis and 2) the clinical characteristics that distinguished the patients who visited twice from patients who were diagnosed on the first visit. A total of 87 patients with appendicitis were seen by pediatricians in the ED from 1987 to 1989. The patients included 43 girls and 44 boys (mean age, 8.9 years). Six patients (7%) were seen twice before the diagnosis of appendicitis was made. They returned to the ED on average 29 hours after the first visit. The ED discharge diagnosis of the six "missed" patients included: probable Campylobacter (n = 1), viral urinary tract infection (n = 1), gastroenteritis (n = 2), and abdominal pain (n = 2). The six missed patients were different from the other patients with appendicitis. They were more likely to have a normal appetite, to have diarrhea, and to be afebrile. All the patients had at least two of the four following signs and symptoms: vomiting, tenderness, guarding, and right lower quadrant (RLQ) pain. At the time of surgery, 23/81 (28%) of the one-visit group had a ruptured appendix, whereas 3/6 (50%) of the missed patients had a ruptured appendix. CONCLUSIONS: 1) Seven percent of the patients were seen twice in our ED before the diagnosis of appendicitis was made.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488137 TI - Pain, punctures, and pediatricians. PMID- 8488138 TI - Central nervous system findings and intussusception: how are they related? PMID- 8488139 TI - Bacterial peritonitis and sepsis presenting as acute gastrointestinal bleeding in patients with portal hypertension. AB - Four children with portal hypertension and ascites developed hematemesis, abdominal pain, and fever as the acute manifestations of bacterial peritonitis. Initial management in the emergency department was directed toward controlling the upper gastrointestinal hemorrhage, and antibiotic therapy was delayed in four of six episodes until ascitic fluid cultures grew Streptococcus pneumoniae. Gastrointestinal bleeding has not been previously reported as a presenting symptom of peritoneal infection. Our clinical experience emphasizes the need for antibiotic therapy during the initial management of children with ascites and hematemesis. PMID- 8488140 TI - Torsade de pointes associated with Astemizole overdose treated with magnesium sulfate. AB - Astemizole (Hismanal-Janssen, New Brunswick, NJ) is a nonsedating antihistamine that has the advantage of a once-daily dosage schedule. This article reports the case of a 14-year-old female who intentionally ingested 270 mg of Astemizole and developed torsade de pointes, a form of polymorphic ventricular tachycardia that is associated with prolongation of the QTc interval. She was successfully treated with magnesium sulfate infusion and had an uneventful recovery over a period of 36 hours. This case illustrates that Astemizole overdose is not benign and should be considered in the differential diagnosis of ventricular tachyarrhythmias. Use of high-dose Astemizole may not be advisable for patients who are at risk for prolongation of the QTc interval. PMID- 8488141 TI - Magnetic resonance imaging for early diagnosis of necrotizing fasciitis. AB - One of the most serious complications of chickenpox is varicella gangrenosa, a form of necrotizing fasciitis. A confounding factor is the frequency of more superficial skin infections during chickenpox, often caused by group A beta hemolytic streptococcus. Because the progression from cellulitis to fasciitis is so insidious, severe tissue necrosis often has occurred before the correct diagnosis is made on the basis of clinical examination. Even today, limb amputation is occasionally required for treatment of gangrenous varicella. In this report, we demonstrate that magnetic resonance imaging can delineate the degree and depth of inflammation within an extremity and, thereby, indicate when the infection is progressing despite antibiotic therapy. Thus, the earlier use of magnetic resonance imaging may facilitate the diagnosis of necrotizing fasciitis. PMID- 8488142 TI - Cervicofacial and thoracic barotrauma following a minor dental procedure. AB - A case of cervicofacial subcutaneous emphysema and pneumomediastinum following a seemingly minor dental procedure is described. This dramatic but usually benign complication of dental work is rare and has not been reported in the pediatric emergency medicine literature. A brief review of this entity and an overview of diagnostic considerations and management are presented. PMID- 8488143 TI - Pediatric herpes zoster with mild cutaneous dissemination. AB - The textbook division of herpes zoster into segmental or disseminated is too simple and limited. Like all diseases, herpes zoster presents as a spectrum of disease. Mild cutaneous dissemination represents a "transition zone" in this spectrum and appears to be a benign clinical variant. This case of pediatric herpes zoster with mild cutaneous dissemination did not need aggressive inpatient treatment with IV agents; appropriate treatment included close follow-up. Optional treatment with high-dose oral acyclovir was also instituted. PMID- 8488144 TI - What dose of epinephrine is being used in pediatric resuscitation? Results of a survey. AB - Standard-dose epinephrine (SDE) currently recommended by the American Heart Association for pediatric resuscitation is 0.01 mg/kg (0.1 ml/kg of 1:10,000 solution). SDE has come under increasing scrutiny; many authors suggest that this dose is too small. We sought to determine current epinephrine dosing practices among physicians practicing pediatric emergency medicine. Half of the members of the American Academy of Pediatrics Emergency Medicine section, selected randomly, were surveyed by a mailed questionnaire. After two mailings, 105 of 162 surveys (65%) were completed by members in practice. Of the 105 responders, 59% described their practice as "pediatric emergency medicine"; 17% as "emergency medicine (children and adults)"; 10% as "general pediatric practice or clinic"; 10% as "critical care"; and 5% as "other." Fifty-one (49%) had completed fellowship training, and 81 (77%) were either PALS or APLS instructors (referred to as "instructors" below). Overall, 72% (76/105) indicated that they use doses larger than SDE. Sixty-five of these (86%) described their dosing practice as "recommended dose initially, then larger dose." Twenty-one percent use SDE less than half of the time, and 16% use a dose 10 to 20 times larger at least half of the time. No responder used doses smaller than SDE. Instructors were more likely to use larger doses than were noninstructors (83% compared with 38%; P < 0.001). In the instructor group, a significantly larger dose was being taught "informally" than "formally" (P < 0.001). This survey was undertaken to determine current dosing practices by a group of physicians who are knowledgeable and experienced in pediatric resuscitation, not to resolve the question of the optimal dose of epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488145 TI - Prehospital curriculum development: a learning objective approach. AB - Prehospital curriculum development is a time-consuming, yet essential, component of emergency medical technician and paramedic education. Over the past several years, much has changed within the EMS system and with the approach to educating the prehospital care provider. Learning is defined as a permanent change in behavior that comes about as a result of a planned experience. This planned experience must include learning objectives that incorporate assessment of presenting signs and symptoms and demonstrate the prehospital care providers' psychomotor skills in providing prehospital care based on that assessment. PMID- 8488146 TI - Intussusception: don't miss the diagnosis! PMID- 8488147 TI - ECG monitors. PMID- 8488148 TI - Leg pain with activity. PMID- 8488149 TI - A 13 year old with seizures and deafness. PMID- 8488150 TI - Use of acyclovir in varicella. PMID- 8488151 TI - Pediatric Emergency Medicine (PEM) Fellowship Curriculum Statement. Curriculum Subcommittee, Section of Emergency Medicine, American Academy of Pediatrics. PMID- 8488152 TI - Epidemiology of ocular complications of childhood head trauma. PMID- 8488153 TI - Analysis of pediatric emergency department telephone calls. AB - This study analyzed incoming telephone calls to an urban county pediatric emergency department (PED). Data were collected by reviewing recorded incoming calls and written logs for two separate months, six months apart. Eight hundred seventeen calls were reviewed. The largest number of calls for both months (15%) was for upper respiratory infection symptoms. Information, fever, and diarrhea were in the next three ranks for both months. Fifty-three percent were about children under one year of age. Over 50% of the calls were received from 4:00 PM to 12:00 AM during both months. The average length of calls was 4.0 minutes. A review of the logs identified 221 (27%) calls to be emergent or urgent; 197 (89%) of these callers were advised to bring the child to the PED. These data suggest that content for a curriculum should be directed toward common pediatric problems regarding young children, focusing on children under one year of age. PMID- 8488154 TI - Modified apical dissection for early continence after radical prostatectomy. AB - A prospective evaluation of urinary continence in 83 consecutive patients undergoing radical prostatectomy using a modified apical urethral dissection is described. Using this technique, complete continence has been achieved in 88%, with stress incontinence in 11% and total incontinence in 1%. Continence was achieved in less than 1 week to a maximum of 16 weeks, with 17% dry during the first week, 53% dry by 6 weeks, and 81% by 3 months. Median time to continence was 5 weeks. Median age of the continent patients was significantly lower than that of incontinent patients. Neither the number of neurovascular bundles resected, the need to reconstruct the vesical neck, nor the number of anastomotic sutures used affected the rate of continence. The described technique, which incorporates the fascia posterior to the urethra into the vesicourethral anastomosis, results in earlier continence after radical prostatectomy, and thereby lessens the morbidity of this procedure. PMID- 8488155 TI - Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo. AB - Prostatic inhibin peptide (PIP), is a 94 amino acid protein which is secreted by the prostate gland in an androgen-independent manner. Previously, it has been demonstrated that PIP appears to inhibit follicle-stimulating-hormone (FSH) secretion by the pituitary and prostate glands. In vitro, the Dunning R3327 rat prostate cancer cell line MAT-LyLu (MLL) cells and the human prostate cancer cell line PC-3, are stimulated to grow in response to exogenous FSH and these effects are blocked by PIP. In vivo, PIP inhibits the growth of the highly metastatic MLL prostate cancer cell line. A comparison of hormone levels in control and PIP treated rats demonstrates a significant inhibition of FSH in treated animals. It appears that, in vivo, PIP may inhibit prostate cancer growth by inhibiting FSH. PIP may represent a novel hormonal treatment for prostate cancer. PMID- 8488156 TI - Ultrasonic diagnosis of 3,2'-dimethyl-4-aminobiphenyl induced tumors in the urogenital organs of F344 rats. AB - The usefulness of transabdominal ultrasonography in the diagnosis of 3,2' dimethyl-4-aminobiphenyl- and testosterone propionate-induced tumors of the urogenital organs was evaluated in F344 rats. Seven mass lesions (1 ventral prostate, 1 dorsolateral prostate, 3 seminal vesicles, and 1 kidney) in the urogenital organs could easily be diagnosed concerning size and localization by ultrasound. Histological examination revealed a lesion in the ventral prostate to be an abscess and the other tumors to be malignant. Three hydronephroses by tumor invasion to the ureter, and six tumors in organs other than the urogenital organs could be detected by ultrasound. The threshold of malignant tumor detection by ultrasound was 7 mm in actual length. The size of the mass lesion estimated by ultrasound correlated well with the direct measurement (r = 0.96). Transabdominal ultrasonography is useful for diagnosing the localization of experimental tumors and accurately measuring their size in the urogenital organs of rats. PMID- 8488157 TI - Insulin-like growth factor I: action and receptor characterization in human prostate cancer cell lines. AB - The role of insulin-like growth factor I (IGF-I) in the growth and development of prostate cancer was studied using established human prostate cancer cell lines. Under steroid and growth factor-free culture conditions, IGF-I significantly stimulated the androgen-independent cell lines PC-3 and DU-145 to incorporate [3H]thymidine into DNA, while the androgen-dependent cell line, LNCaP, was not affected. However, in the presence of dihydrotestosterone (DHT), DNA synthesis of LNCaP cells was stimulated by IGF-I in a dose-dependent manner. None of the cell lines tested secreted an immunoreactive level of IGF-I into their conditioned medium. Characterization of receptors by ligand binding assays revealed that all prostate cancer cell lines tested express specific binding sites for IGF-I with similar dissociation constants (0.23-0.39 nM). Crosslinking studies supported the suggestion that 125I-IGF-I was bound to a receptor on these cells. The IGF-I receptor concentrations of androgen-independent cell lines were significantly higher than those of the androgen-dependent cell line. Androgen appeared to affect neither the expression of IGF-I receptors nor the secretion of IGF-I. The results suggest that IGF-I may play an important role in stimulating the growth and progression of prostate cancer. PMID- 8488158 TI - Immunohistochemical study of phospholipase A2 in bovine prostate. AB - Approximately 1,100-fold purified phospholipase A2 (PLA2) from bovine prostate was injected into rabbit to prepare polyclonal antibodies. Antibodies produced showed specific immunoprecipitation only with the purified enzyme, as well as with homogenate of bovine prostatic tissue. By Western blot analysis or by immunodiffusion test, no cross-reactivity with PLA2 purified from human seminal plasma, bovine pancreas, Crotalus adamanteus venom, or with partially purified PLA2 from bovine seminal vesicle fluid or Cowper's glands was observed. Using the indirect peroxidase technique, PLA2 was localized in the cytoplasm of bovine prostatic epithelial cells. By immunogold microscopy, this enzyme was directly visualized inside the lysosomes, as well as in the endoplasmic reticulum of the glandular epithelial cells. Enzyme activity was localized in two principal subcellular sites: the mitochondria and lysosome-enriched fraction, and in the microsomal fraction. PMID- 8488159 TI - [The bioanalytical uses of the luciferase from fireflies (a review)]. AB - Main principles of the bioluminescent microassay with the use of firefly luciferase are considered. Literature data and own experimental results of the author on application of luciferase in microbiology, clinical biochemistry, and express assays for antibiotic sensitivity and resistance to biocorrosion are generalized. New approaches to the use of luciferase for the detection of enzyme labels in EIA and for the nonradioactive detection of DNA probes are discussed. PMID- 8488160 TI - [The characteristics of the regulation of lysine biosynthesis in Streptococcus bovis]. AB - The effect of threonine and methionine on the growth of and lysine synthesis in Streptococcus bovis st. A024/85 was studied. The character and the degree of manifestation of growth and regulation effects of these amino acids depend on their contents in the fermentation medium. The target in the regulation of lysine biosynthesis is aspartate kinase, whose synthesis is controlled by threonine and methionine. Lysine excretion was stimulated by the addition of a low concentration of dimethylsulfoxide in the medium during fermentation. PMID- 8488161 TI - [The action of exogenous RNAse on the cells of lower eukaryotes]. AB - We studied the mechanism of growth-stimulating effect of various compounds using an exogenous RNase-micromycete model and found that the treatment with microdoses of RNase intensified the reproduction of the yeast Candida valida and growth of Aspergillus fumigatus. At the same time the respiration activity of yeast cells and fungal mitochondria as well as succinate dehydrogenase activity increased. The secretion of total protein, cellulase and cellobiase changed in the presence of RNase in the growth medium. Electrophoretic mobility of Candida valida cells enhanced by 20%. The RNase stimulating effect on microbial cells seems to result from changes in characteristics of the cell surface. PMID- 8488162 TI - [The stimulation and inhibition of the secondary growth of microorganisms by metals]. AB - A selective (inhibitory and stimulatory) effect of metal salts on secondary growth of representatives of 5 genera of actinomycetes and 5 genera of fungi was established. The effect of metal salts on the growth of procaryotes and eucaryotes have both common and specific features. Differences in the biosorption of metals (Mo, Mn, Cu, Zn) by cells of primary and secondary growth were revealed. The possibility of enhancing the sorption capacities of cells in secondary colonies of mycelial microorganisms should be taken into account as selecting cultures for the purification of environment from heavy metals. PMID- 8488163 TI - [Associationism: the force of consensus]. PMID- 8488165 TI - [The ICN: a social force]. PMID- 8488166 TI - [Associationism for the defense of civil rights]. PMID- 8488164 TI - [Who is safeguarding the profession?]. PMID- 8488167 TI - [Law 421 of 23 October 1992 on the Reorganization of Teaching in Health Matters]. PMID- 8488168 TI - [Unity in plurality--associationism: force and progress in the nursing profession]. PMID- 8488169 TI - Antihypertensive activity of the novel, nonpeptide angiotensin II receptor antagonists BIBS 39 and BIBS 222 in conscious renal hypertensive rats. AB - BIBS 39 and BIBS 222 are novel, nonpeptide angiotensin II receptor antagonists with a benzimidazole structure. These compounds, in contrast to the angiotensin II receptor subtype 1 (AT1) selective drug DuP 753, also display affinity for the angiotensin II receptor subtype 2. Their antihypertensive activity was established in conscious renal hypertensive rats. BIBS 39, BIBS 222 and DuP 753, when administered intravenously, caused a substantial dose-dependent antihypertensive effect with very similar ED30 values of approximately 2 mg/kg. The antihypertensive effect was accompanied by mild and transient reflex tachycardia. Captopril, when administered directly after the maximally effective dose of the three angiotensin II receptor antagonists, caused no further fall in blood pressure. This finding indicates that these angiotensin II receptor antagonists had caused a functionally effective suppression of the activity of the renin-angiotensin-aldosterone system. BIBS 222 had a longer duration of antihypertensive action than its congener BIBS 39. The hemodynamic pattern of DuP 753 was somewhat more complex; after a rapid fall and recovery blood pressure was maintained for a long time at a level somewhat below the control value. BIBS 39 and BIBS 222 appear to be effective antihypertensives in the model of the renal hypertensive rat. Their activity is likely to be associated with AT1 receptor blockade. PMID- 8488170 TI - Fluid resuscitation improves survival of endotoxemic or septicemic rats: possible contribution of tumor necrosis factor. AB - The present study was designed to investigate the effects of fluid administration on survival in endotoxemic or septicemic male Sprague-Dawley rats. Endotoxemia was induced by intravenous injection of Escherichia coli lipopolysaccharide (LPS), and septicemia produced by cecal ligation and puncture (CLP). In endotoxemic animals deprived of fluid resuscitation, 7-day survival following injection of LPS at doses of 1, 3, or 10 mg/kg LPS were 70% (n = 10), 30% (n = 10), and 0% (n = 10), respectively. In rats resuscitated with 3.3 ml/kg/h of 0.9% NaCl, the dose-response curve for survival was shifted 5-fold rightward in a parallel manner (p < 0.001, between the fluid-resuscitated and nonfluid resuscitated LPS groups), indicating a reduced sensitivity to the effects of LPS following fluid resuscitation. LPS increased serum tumor necrosis factor (TNF alpha) concentrations in fluid-resuscitated endotoxemic animals from a baseline value of 20 U/ml to 2,350 U/ml at 1 h, which returned to 200 U/ml at 2 h. In endotoxemic animals not receiving fluid resuscitation, serum TNF alpha levels at 1 and 2 h were 5-fold and 27-fold higher, respectively, than in fluid resuscitated animals. There were no differences in arterial blood pressure or heart rate between the two groups of endotoxemic animals; total peripheral resistance was significantly lower at 1 h, and cardiac index was significantly greater at 3 h in the fluid-resuscitated LPS group; otherwise there were no further differences in hemodynamic parameters between the two groups. The survival rate at 4 days following CLP without fluid resuscitation was 14%, whereas CLP with fluid resuscitation improved survival to 74% (p < 0.01). TNF alpha was undetectable (i.e., < 20 U/ml) in the serum of animals subjected to CLP. The improvement in survival with fluid infusion in the LPS and CLP models cannot be attributed to catheter implantation, or to improved hemodynamic parameters in the LPS model. The improvement in survival in the LPS model with fluid infusion was associated with attenuated increases in TNF alpha levels. Furthermore, these studies illustrate that fluid-resuscitated and nonfluid resuscitated experimental animal models should not be considered equivalent. PMID- 8488171 TI - Microsomal acyl glucuronidation: enzyme-kinetic studies with labile glucuronides. AB - Because of the labile nature of acyl glucuronides under physiologic conditions, metabolic rates of formation calculated using traditional methods may be confounded by concomitant rates of degradation. True metabolic formation rates may be approximated by stabilization of the metabolic product or by purifying the metabolite and calculating its degradation rate under similar conditions to that utilized in the formation experiments. This latter degradation rate is used to correct the apparent formation parameter in the absence of inhibitors. The advantages and limitations of each approach are reviewed employing studies to characterize rates of acyl glucuronidation for nonsteroidal antiinflammatory drugs. PMID- 8488172 TI - Sulphydryl-containing agents and the prevention of duodenal ulcer relapse. AB - This prospective randomized double-blind controlled study investigated whether sulphydryl-containing agents protect against the recurrence of duodenal ulceration. To this end, DL-cysteine (200 mg 4 times daily) and DL-methionine methyl sulphonium chloride (MMSC, 500 mg 4 times daily) were administered orally. Three hundred and six consecutive smokers with previous symptomatic endoscopy proven duodenal ulceration which had been shown endoscopically to have healed were randomized to receive for 1 year either placebo, cimetidine 400 mg at bedtime, cysteine, or MMSC. In 221 patients evaluable for efficacy, the cumulative relapse rate at 1 year was: placebo 64%, cimetidine 30%, cysteine 11% and MMSC 12%. Cimetidine was significantly effective in preventing ulcer relapse (p < 0.01), however cysteine and MMSC were more effective in this respect (p < 0.05). In the patients who relapsed, ulcer recurrence tended to occur early on placebo but to be evenly distributed over the year on active therapy. In all the study groups, the relative frequency of symptomatic to silent relapse was similar in the first and second halves of the year and was comparable among these groups. These results show that sulphydryl-containing agents significantly reduce the recurrence rate of duodenal ulceration. PMID- 8488173 TI - Effect of naloxone on the antipyretic action of acupuncture. AB - The effect of the opioid antagonist naloxone on the antipyretic action of acupuncture was studied in rabbits. Naloxone (0.1-0.2 mg/kg) when administered intravenously prior to acupuncture reduced the intensity and duration of the antipyretic action of acupuncture only in the initial stage. The data suggest participation of an endogenous opioid system in initiation of a number of responses mediating the antipyretic effect of acupuncture. PMID- 8488174 TI - Norcocaine and N-hydroxynorcocaine formation in human liver microsomes: role of cytochrome P-450 3A4. AB - Cocaine was metabolized to norcocaine by microsomes prepared from lymphoblastoid cells expressing transfected human P-450 3A4. The specific activities of norcocaine formation by microsomes prepared from three human liver samples correlated with the amount of P-450 3A immunoreactive protein detected by immunoblot. Triacetyloleandomycin, a specific inhibitor of P-450 3A isoforms, inhibited formation of norcocaine from cocaine, but not formation of N hydroxynorcocaine from norcocaine. The chemical identity of the norcocaine and N hydroxynorcocaine produced by human liver microsomes was established by combination of gas chromatography and mass spectrometry. Thus, human P-450 3A4 is a cocaine demethylase, and P-450 isoforms of the 3A family are responsible for the majority of norcocaine production by human hepatic microsomes. PMID- 8488175 TI - A transputer based three-dimensional dynamic cardiac imaging system. AB - In Aberdeen, a single-section transverse emission scanner has been adapted to trigger off patient ECG signals, allowing for the acquisition of gated blood pool tomograms at a number of slice levels through the patient's heart. This paper describes a system for the routine generation and display of surface rendered images derived from this data using a transputer based hardware system. Surface rendering algorithms have been implemented to provide an indication of the distribution of the cardiac blood pool in three dimensions, whilst the additional use of colour and/or cine sequences provide a succinct method of representing the extra information provided by gated acquisition. The transputer provides sufficient computing power to produce rendered views at a rate of about 1 frame per second, thus putting view selection fully under operator control. The success of the system described is reflected in its routine use in a busy clinical department. PMID- 8488176 TI - Measurement of the optical properties of the skull in the wavelength range 650 950 nm. AB - The optical properties of samples of bone from pig skull have been measured over the wavelength range 650-950 nm. The scattering phase function was measured on thin samples of the bone using a goniometer, and a value for the mean cosine g, of the scattering angle, was calculated. The scattering and absorption coefficients, mu s and mu a were then determined from measurements of diffuse reflectance and transmittance made with a pair of integrating spheres, by a step wise search through a table of diffuse reflectance and transmittance versus mu a and mu s generated by a Monte Carlo model incorporating the measured scattering phase function. Values for g measured on six samples varied from 0.925 +/- 0.014 at 650 nm to 0.945 +/- 0.013 at 950 nm. Corresponding values for mu a and mu s measured on 18 samples were mu a = 0.04 +/- 0.002 mm-1, mu s = 35 +/- 0.7 mm-1 at 650 nm to mu a = 0.05 +/- 0.002 mm-1, mu s = 24 +/- 0.6 mm-1 at 950 nm. PMID- 8488177 TI - Time-domain dielectric spectroscopy applied to cell suspensions. AB - A precision difference time-domain reflectometry (TDR) technique is described for the investigation of the dielectric properties of cell suspensions. The dielectric spectra obtained for erythrocytes using TDR are comparable with those reported in previous dielectric studies employing frequency-domain technique. PMID- 8488178 TI - Nursing case management for children undergoing craniofacial reconstruction. AB - With consumers and providers alike expressing dissatisfaction with today's health care delivery system, case management has helped to achieve an effective balance among expected outcomes, the process of care delivery, and cost. This article describes nursing case management for children undergoing craniofacial reconstruction and how case management plans can be implemented. PMID- 8488179 TI - Nutrition and wound healing. AB - As many as 50% of medical-surgical patients in major metropolitan medical centers have some degree of protein-calorie malnutrition, which is associated with increased morbidity and mortality. Malnutrition affects wound healing in these patients, and nurses must assess and help these patients meet their nutritional needs. PMID- 8488180 TI - Fibrocystic breast disease: every woman is at risk. AB - Fibrocystic breast disease refers to a constellation of breast changes observed in premenopausal women, and 90% of all women experience evidence of pathophysiologic changes in the breast during their lifetime. Although most breast changes are harmless, women need to be concerned with the increased risk of breast cancer, one of the leading causes of death in women in the United States. PMID- 8488181 TI - American Nurses Association philosophical statement on ethics and human rights. AB - The purpose of this statement is to describe some of the features of human rights and to indicate how human rights and ethics are related. Human rights are assertions that call for treating human beings as ends in themselves, rather than as means to the goals and purposes of others. The principle of justice is one point at which issues of ethics and human rights intersect. PMID- 8488183 TI - Sterilization in the O.R. PMID- 8488182 TI - Development of the certification examination for plastic surgical nursing. PMID- 8488184 TI - Who's the boss? PMID- 8488185 TI - Nursing research: a vital resource to the profession. PMID- 8488186 TI - A team approach in the treatment of craniofacial deformities. AB - The treatment of the child with craniofacial deformities is multifaceted. Health care professionals must take a "team approach" in providing care, and address the physical, psychological, and sociological needs of the child and family. PMID- 8488187 TI - Activity on the central nervous system of Himanthalia elongata; Part II. AB - We report the effects on the central nervous system (CNS) and on analgesic activity of a fraction (F2) obtained from a Himanthalia elongata extract. The fraction was assayed for effects on spontaneous locomotor activity, d-amphetamine induced hypermotility, motor coordination, muscular relaxation, rectal temperature, sodium pentobarbital-induced hypnosis, and pentylenetetrazole induced convulsions. Analgesic activity was evaluated using the hot plate test and the Randall-Selitto test (1). The fraction caused significant reductions in spontaneous locomotor activity, hypermotility, rectal temperature, and motor coordination and postponed pentylenetetrazole-induced death, but no effect was noted on muscle relaxation or the duration of sodium pentobarbital-induced sleep. The fraction exhibited central analgesic effects in the hot plate and Randall Selitto tests. PMID- 8488188 TI - Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK 501) and their combination Gincosan (PHL-00701). AB - In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs. The favorable effects on learning and memory of the combination of G115 plus GK501 and the other pharmacological activities inherent in the extracts characterize this combination, offered as Gincosan as a particularly promising drug in geriatric practice. PMID- 8488189 TI - alpha-Asarone toxicity in long-term cultures of adult rat hepatocytes. AB - In this work we studied the toxic effects of alpha-asarone, a hypolipidemic active principle of Guatteria gaumeri Greenman, on long-term cultures of adult rat hepatocytes cultivated on a feeder layer of 3T3 cells. The exposure for one and two weeks to alpha-asarone (1-50 micrograms/ml) produced intracytoplasmic lipid droplets and at higher concentrations (25-50 micrograms/ml) retraction of the hepatocyte cords and cell detachment. Ultrastructurally, the treated cultures (10 micrograms/ml) showed enlargement and vacuolization of the mitochondria in addition to lipid droplets. The triacylglycerol content increased up to 2.3-fold in the cultures treated for one week with 50 micrograms/ml, whereas the protein content per culture, a rough estimate of cell number and viability, decreased by up to 53% in the cultures treated for two weeks with 50 micrograms/ml. The synthesis and secretion of proteins, measured by the incorporation of [3H] leucine into cellular and secreted macromolecules, decreased also in the cultures exposed. After one and two week exposure to 50 micrograms/ml of alpha-asarone, the secretion of labeled proteins decreased by 53 and 67%, respectively, whereas the synthesis of cellular and total proteins decreased by 48-67%, respectively. The secretion of proteins was the most sensitive parameter of alpha-asarone toxicity. The mean inhibitory dose (ID50), i.e, that producing 50% inhibition in the incorporation of the labeled precursor, was 22.12 and 5.04 micrograms/ml after one and two weeks exposure, respectively. Our results show that long-term exposure to micromolar concentrations of alpha-asarone produces morphologic and ultrastructural alterations, triacylglycerol accumulation (fatty liver), and inhibition of protein synthesis and secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488190 TI - Inhibition of lipid synthesis and secretion in long-term cultures of adult rat hepatocytes by alpha-asarone. AB - In this work we studied the effect of alpha-asarone, a hypolipidemic active principle of Guatteria gaumeri Greenman, on hepatic lipid metabolism using adult rat hepatocytes cultured on a feeder layer of 3T3 cells. These cultures synthesize and secrete for at least two weeks various lipids from [14C]-acetic and [14C]-oleic acid. Exposure for one or two weeks to 10 micrograms/ml of alpha asarone decreased the secretion of various lipids to the culture medium; triacylglycerol secretion was inhibited by 80-97%, phospholipid secretion by 70 87%, cholesterol by 64-70%, and cholesterol esters by 50-92%. The incorporation of [14C]-acetic acid into cellular lipids decreased by 30-81% and that of [14C] oleic acid into phospholipids by 25-47% whereas the incorporation of [14C]-oleic acid into triglycerides and cholesterol esters increased 3.2 fold and by 28-36%, respectively. Similarly, the activities of glycerol-3-phosphate dehydrogenase and malic enzyme, marker enzymes of glycerolipid and fatty acid synthesis, decreased by 22-50% and 30-76%, respectively. Our results show that the exposure of the 3T3 hepatocyte cultures to micromolar concentrations of alpha-asarone significantly inhibits lipid secretion and probably lipid synthesis. They also suggest that at least part of the hypolipidemic effect could be due to a decrease in the secretion of lipids (i.e., lipoproteins) by the hepatocytes. PMID- 8488191 TI - Effects of Chlorella stigmatophora extract on the central nervous system. AB - At the level of the central nervous system an aqueous extract of the marine microalga Chlorella stigmatophora (Butcher) (Chlorophyceae) showed anti dopaminergic-type activity in assays of its effects on spontaneous motor response, rectal temperature, motor coordination, amphetamine-induced hypermotility, exploratory conduct, muscle relaxation, catalepsy, conditioned avoidance responses, oxotremorine-induced cholinergic syndrome, and pentylenetetrazole-induced convulsions. PMID- 8488192 TI - Crude extracts and two linear diterpenes from Cystoseira balearica and their activity. AB - Crude extracts of Cystoseira balearica were submitted to pharmacological investigations. The chloroform-methanol residue caused relaxation of the rat aortic musculature and an inhibitory action on the guinea pig atria. The fractionation of this crude extract gave two active diterpenoids, eleganolone (1) and elegandiol (2), the latter has not previously been isolated from this alga. These pure components, never before tested, showed a higher activity when compared with the crude residue. PMID- 8488193 TI - Inhibition of cytochrome P-450(11)beta by some naturally occurring acetophenones and plant extracts from the shrub Salsola tuberculatiformis. AB - Ingestion of the Namibian shrub Salsola tuberculatiformis Botsch. by virgin female rats extends the dioestrus period of their oestrous cycles. Methanol extracts of the plant also inhibit adrenal steroidogenesis in the rat. With the aid of a bioassay, in which vaginal smears were used to follow the oestrous cycles of virgin rats, active fractions could be obtained which indicated that the plant contains a number of active compounds. The most active of these are highly unstable compounds which could not be isolated in pure form. However, two stable but less active compounds were identified as 4-hydroxyacetophenone and 4 hydroxy-3-methoxyacetophenone. This study investigated the influence of these acetophenones, their glucosides, and that of ethanol extracts of S. tuberculatiformis on adrenal steroidogenesis. Acetovanillon, a structurally related natural product also known as compound Z, was included in this study. Results show that the shrub contains active substances which interfere with adrenal 11 beta-hydroxylase, the terminal enzyme in glucocorticoid biosynthesis. This interaction with the cytochrome P-450(11)beta-dependent hydroxylase, as well as the inhibition of the conversion of deoxycorticosterone to corticosterone, was used to develop two sensitive and reliable assays for the rapid identification of small amounts of active compounds from S. tuberculatiformis. PMID- 8488194 TI - Effects of kampo (Japanese herbal) medicine "sho-saiko-to" on DNA-synthesizing enzyme activity in 1,2-dimethylhydrazine-induced colonic carcinomas in rats. AB - Sho-Saiko-To (SST) is a modified Japanese traditional Chinese herbal medicine containing seven medical plants: Bupleuri radix, Pinelliae tuber, Suxtallariae radix, Zizyphi fructus, Ginseng radix, Glycyrrhizae radix, and Zingiberis recens rhizoma. This preparation has been used in the treatment of some inflammatory diseases of the respiratory system and chronic hepatitis. In the present study, the effects of SST were investigated on the activities of DNA-synthesizing enzymes in 1,2-dimethylhydrazine (DMH)-induced colonic carcinomas in rats. Six week administration of SST prevented nearly 100% of the body weight loss and the final number of the colonic carcinomas compared to those in the rats treated with DMH alone, and suppressed the enhanced activities of thymidylate synthetase (TS) and thymidine kinase (TK) which were involved in the de novo and salvage pathways of pyrimidine synthesis, respectively, in DMH-induced colonic carcinomas. These results indicate that SST may show directly and/or indirectly inhibitory effects on the development of colonic carcinomas. PMID- 8488195 TI - [Biological standardization of Ginkgo extracts]. AB - The determination of the inhibition of PAF (platelet-activating factor)-induced platelet aggregation has been proposed as a biological standardization method for commercially available Ginkgo biloba extracts by measuring the characteristic pharmacological effect of ginkgolides in vitro. The determination is specific for ginkgolides A, B, C, and J and is not influenced by other constituents present in Ginkgo biloba extracts. IC50 values of ginkgolide B can be used to standardize various Ginkgo extracts produced by special extraction methods with respect to equi-effective ginkgolide B contents. In order to compare values obtained by a chemical-analytical procedure with those obtained by the biological assay, the equi-effective total ginkgolide content of each Ginkgo extract had to be calculated. Accordingly, the concentrations of the individual ginkgolides in the various Ginkgo extracts were determined chromatographically by assaying ginkgolides as trime-thylsilyl derivatives. Their individual contributions towards the measured in vitro effects were derived from their respective IC50 values. The calculated equi-effective total ginkgolide contents of the Ginkgo extracts were in good agreement with those obtained by gas chromatography. The results demonstrate that, in addition to a chemical standardization, the biological standardization of Ginkgo extract preparations is also feasible. PMID- 8488196 TI - Tetragalloylquinic acid, the major antiasthmatic principle of Galphimia glauca. AB - In the search for antiasthmatic principles in plant drugs, a bioguided fractionation of an alcoholic extract of Galphimia glauca was performed using a plethysmographic in vivo model. Tetragalloylquinic acid (G1), which was found together with other compounds (gallic acid, methyl gallate, ellagic acid, and flavonoid acylglycosides), showed the highest activity against bronchial hyperreactivity and allergic reactions. Using mass and NMR spectroscopy in combination with energy calculations, the structure G1 was elucidated as tetra-O galloylquinic acid. Depending on the solvent used, the quinic acid skeleton can occupy a fixed conformation or several interconverting ones on the NMR time scale. PMID- 8488197 TI - Isodunnianin: a new sesquiterpene enhancing neurite outgrowth in primary culture of fetal rat cerebral hemisphere from Illicium tashiroi. PMID- 8488199 TI - [The psychosociological assessment of suicidal behavior among soldiers]. PMID- 8488198 TI - [Psychological, neuroendocrinological and ethnological aspects of sexual variation, deviations and clinical observations]. PMID- 8488200 TI - [Life stress events and individual reactions to stress in relation to illness]. AB - Data was collected from 90 persons in relation to the level of their emotional reactions to life's difficulties as well as to the number of somatic symptoms. It was concluded that falling ill with certain infectious diseases and some psychosomatic states are related to the increased level of emotional processes and the number of psychosomatic symptoms to stress. PMID- 8488201 TI - [Psychopathological characteristics of the consequences of obstructive sleep apnea prior to and 3 months after therapy]. AB - The aim of the research was to discover the level of change observed in cognitive functions and personality variables in patients ill with obstructive sleep apnea prior to and after CPAP treatment. Data was collected from 20 male patients ill with a severe form of obstructive sleep apnea whose physiological symptoms were correlated with the results of cognitive functions and personality variables. It was concluded that obstructive sleep apnea patients have lowered; attention, concentration, speed of learning verbal and visual stimuli and speed of learning visual-motor tasks. An increased level of depression was noted together with increased anxiety and psychological tension. In half of the group irregular EEG recordings and a pathological result on the Benton Test suggests organic damage to the CNS. These changes were negatively correlated with amounts of REM and 3 + 4 NREM sleep, but were positively correlated with the level of sleep hypoxemia. The results suggest that after 3 months of CPAP treatment affect improved significantly. The observed tendency for cognitive functions to improved was not statistically significant. PMID- 8488202 TI - [The role of anxiety as motivation in the genesis of manslaughter]. AB - Presented below are the results of comparative analysis of the motivational role of anxiety in man-slaughter based on six subgroups of perpetrators isolated with the help of cluster analysis according to the types and kinds of leading themes of their action. The statistical analysis of the data of a 105 cases of perpetrators of man-slaughter revealed that anxiety played a differentiating role in the psychological mechanisms which are supposed to lay at the bottom of the crime of man-slaughter. This was especially true of those actions governed by psychological processes which are concerned with the relationship between anxiety and the type and level of interpersonal aggression. It may be concluded that aggression, as well as the anxiety at its base, differ as to their genesis, motivation and course. The results do not support a single universal concept about the actions of perpetrators of man-slaughter, but support the heterogeneity of personality factors of such people, the criminogenic factors of situations and the motivational mechanisms which lead to such action. PMID- 8488203 TI - [The influence of information on the diagnosis of short-term prognosis in schizophrenia]. AB - Data was collected from 60 patients ill for the first time with schizophrenia. In 30 cases a nosological diagnosis was given while in the rest of the patients a syndrome diagnosis was placed. In the follow-up conducted 3 years later it was revealed that the groups basically do not differ from each other in the course of the illness or the clinical picture but they do differ from each other in their job adjustment. PMID- 8488204 TI - [Altered states of consciousness: theoretical models and concepts]. AB - The main contemporary theoretical models and concepts of altered states of consciousness are reviewed. Analysis of the literature indicates that nowadays, psychology recognizes the existence of different levels of consciousness. The achievements of the psychology of consciousness are helpful in research, but they have a very limited application in psychiatric practice. PMID- 8488205 TI - [Applications of computer database in prospective studies on the mortality of patients with diagnosis of schizophrenia]. AB - The efficacy of epistemological research including the analysis of mortality rates depends to some extent on the ability to make use of registration systems and the processing of data. In the paper presented below the author outlines the application of a programme-dBase III plus, created for computer data bases and its use in the assessment of a prospective study of mortality of patients with a schizophrenic diagnosis. Three data bases (S295.DBF, SB295.DBF, GUS1982.DBF) of varying sizes were created, each of which possessed specific categories of information. PMID- 8488206 TI - The horror! The horror! Reflections on our culture of violence and its implications for early development and morality. AB - This commentary draws on two dimensions of chronic community violence, with thoughts that have been mobilized by the foregoing contributions. One concerns the importance of culture and the other concerns the importance of thinking about early development. Culture permeates all of our actions, and we are in a culture of violence. In other papers in this issue, Richters and Martinez point out that the United States is the most violent country in the industrialized world, and Ciccheti and Lynch state that violence "is becoming a defining characteristic of American society." We are fascinated by violence and in an implicit way we love violence-a fact that we need to acknowledge. Our fascination with violence in American culture is permeating and deep, and, as horrible as it is, I believe we need to face it in order to try to counter it. PMID- 8488207 TI - Impact of violence on children and adolescents: report from a community-based child psychiatry clinic. AB - The Children's National Medical Center is located in the inner-city area of Washington, DC. As is nationally now well publicized, the drug-related violence in Washington has earned the area the dubious title of "murder capital of the world." Our outpatient child and adolescent psychiatry clinic at Children's Hospital provides walk-in services during daytime hours, Monday through Friday. Access to services is available at other times through the emergency room. PMID- 8488208 TI - Children in poverty: resilience despite risk. AB - Two objectives provided the focus for the Conference on Community Violence and Children's Development that was jointly sponsored by the National Institute of Mental Health and the John D. and Catherine T. MacArthur Foundation. One was to examine the evidence for deficit behaviors that characterized children reared in poverty; the second was to identify the characteristics of children who sustained their competencies despite being reared in comparable environments. These dual objectives took this form: "What can we conclude from studies of children, their families, and environments about characteristics that predispose children to maladjustment following exposure to violence, and about characteristics that protect children from such adjustment problems following, or in the midst of, violence exposure?" PMID- 8488209 TI - The NIMH community violence project: II. Children's distress symptoms associated with violence exposure. AB - The rising tide of violence in American cities has placed the causes and consequences of violence squarely on the public health agenda. The U.S. Government's Year 2000 National Health Promotion and Disease Prevention Objectives includes a full chapter devoted to violence issues and delineates a number of goals and programs aimed at reducing the number of deaths and injuries associated with violence (Public Health Service 1990). Notably absent from these objectives, however, is attention to the possible adverse psychological consequences of exposure to acute or chronic violence. Nonetheless, in light of numerous media reports of children's exposure to community violence and recent reports documenting high levels of exposure even among very young children (Richters and Martinez 1993), it is reasonable to question whether the risks of exposure extend beyond death and physical injury to psychological well-being. PMID- 8488210 TI - Community violence and children's development: toward a research agenda for the 1990s. AB - The United States is the most violent country in the industrialized world particularly for young people. Homicide in the United States ranks as the second leading cause of death among those between 15 and 24 years of age (Earls et al. 1991). Males, especially, are at high risk. As indicated in Figure 1, those between 15 and 24 years of age were more likely to be murdered than their counterparts in all 22 other developed countries for which comparable homicide statistics were available during 1986-1987 (Fingerhut and Kleinman 1990). Young males were 4 times more likely to be murdered than their counterparts in the next highest country, Scotland; 7 times more likely than young males in Canada; 21 times more likely than those in West Germany; and 40 times more likely than same age males in Japan. Moreover, the U.S. homicide rate for Black males (15 and 24 years) was more than 7 times the homicide rate for White males in this age range. These figures are all the more alarming in light of the fact that homicide rates in major U.S. cities have increased steadily since these data were recorded. PMID- 8488211 TI - Chronic community violence: what is happening to our children? AB - Chronic violence is a growing problem in our society today as evidenced, among other factors, by the ever-increasing murder rate in many of our large urban centers in the United States. Emphasis has begun to be placed on chronic violence, causes that may contribute to it, and the impact of this violence on cities and the country at large. While concern has been expressed, we still have not addressed adequately, nor do we fully understand, the effects on the children who must grow up in environments where they are repeatedly being exposed to significant levels of violence. PMID- 8488212 TI - Community violence and children on Chicago's southside. AB - This report summarizes a program of study on African-American children and violence conducted by a comprehensive community mental health center on the southside of Chicago. The research, which looked at exposure to violence, self reports of aggression, and possible interventions, grew out of: (1) an awareness of the enormous amount of familial and extrafamilial violence in the black community; (2) clinical experiences that indicated that victimization and covictimization (i.e., victimization of close others) were often significant factors in the lives of the mentally ill; (3) a growing uneasiness, and indeed curiosity, over the extent to which children were witnessing these events and the impact of this witnessing, particularly on their own levels of aggression; and (4) a belief that the integrity of the black community was being threatened by the violence and that solutions must be sought. PMID- 8488213 TI - Children's exposure to community violence: following a path from concern to research to action. AB - This paper discusses the antecedents and current progress of an ongoing program of research on the nature, extent, and consequences of children's direct and indirect exposure to violent events and settings. Involvement in such research has sensitized the authors to difficult ethical and methodological challenges that, we believe, merit consideration by mental health scientists and policy markers. Resolution of those challenges has substantive implications for both subsequent research and the application of resultant findings. PMID- 8488214 TI - Community violence, children's development, and mass media: in pursuit of new insights, new goals, and new strategies. AB - Community violence that victimizes children is an unmitigated evil that is exacerbated by vast economic and social forces that leave people in central cities and the rural countryside adrift on seas of rolelessness, hopelessness, group disintegration, and alienation. The contemporary drug scene and the easy availability of guns greatly intensify violence on a local scale, while crimes of violence, especially with guns, appear to be level or declining in the nation as a whole. Claims that the persistently high levels of violence in mass media, mostly television, are largely responsible for violence in society represent narrow views of very large issues. These narrow views overlook essential elements of both phenomena--violence and media. Direct models of interpersonal violence in families and in the community probably give rise to more violent behavior than indirect models in media. Disinhibitory and provocative aspects of media probably do as much or more to trigger violent behavior than violent narratives and violent actions. Comprehensive meta-analysis indicates that prosocial messages on television can have greater effects on behavior than antisocial messages. These data support the contention that mass media can play a strong and positive role in alleviating some of the distress of victims of community violence, and in redirecting the behavior of some of its perpetrators so as to protect the children. PMID- 8488215 TI - The NIMH community violence project: I. Children as victims of and witnesses to violence. AB - The 1980s witnessed an extraordinary increase in community violence in most major cities across the United States. In 1990 the homicide rate in Boston increased by 45% over the previous year; in Denver, by 29%; in Chicago, Dallas, and New Orleans, by more than 20%; in Los Angeles, by 16%; in New York, by 11%. In Washington, DC, which has the highest per capita homicide rate in the country, the 1990 murder rate set an all time record in the District's history (Escobar 1991). Across the country, 1 out of 5 teenage and young adult deaths was gun related in 1988 - the first year in which firearm death rates for both Black and White teenagers exceeded the total for all natural causes of death combined. Also in 1988, the firearm homicide rate for young Black males increased by 35%, and Black male teens were 11 times more likely than their White counterparts to be killed by guns (Christofel 1990). PMID- 8488216 TI - Child sexual abuse: a model of chronic trauma. AB - Although there is a general consensus among concerned professionals that exposure to community violence is likely to be stressful and may contribute significantly to immediate and long-term mental health problems, there is virtually no empirical research on either its acute or enduring effects. In the absence of data, investigators planning research in this area must look to other studies of the impact of chronic environmental trauma on children, including the effects of war and child maltreatment. Research on child abuse provides an important source of information on the effects of trauma on children because it draws on both prospective and retrospective studies crossing a variety of theoretical perspectives and disciplines. The existence of data on both the acute impact of abuse on children and its chronic effects and outcomes in adults informs the generation of developmentally based psychological and biological hypotheses. This paper utilizes data from research on the acute and chronic effects of sexual abuse to discuss three broad hypotheses that may be relevant to the study of the effects of community violence on children. PMID- 8488217 TI - Toward an ecological/transactional model of community violence and child maltreatment: consequences for children's development. AB - In recent decades it has become increasingly apparent that violence affects a significant proportion of families in the United States (Bureau of Justice Statistics 1983). Violence, in fact, is becoming a defining characteristic of American society. A recent comparison of the rates of homicide among 21 developed nations indicates that the United States has the highest homicide rate in the world, and its rate is more than four times higher than the next highest rate (Fingerhut and Kleinman 1990). What is even more alarming is the high incidence of violent death and injury for children and adolescents in the United States. Acts of violence are the cause of death for over 2000 children between the ages of 0 and 19 years each year, and more than 1.5 million children and adolescents are abused by their adult caretakers each year (Christoffel 1990). PMID- 8488218 TI - An investigation into the internal structure of DSM-III antisocial personality disorder. AB - The present study examined the DSM-III antisocial personality disorder by examining endorsements of each of the DSM-III criteria to obtain various indices, including interrater reliability, sensitivity, specificity, positive and negative predictive power, alpha levels, and item (criterion)-total correlations. 112 psychiatric inpatients were rated on the Structured Interview for DSM-III Personality. 11 patients were accorded a diagnosis of antisocial personality disorder, 65 had other forms of personality disorders, and 36 received no personality disorder diagnosis. The antisocial criteria successfully discriminated patients with antisocial personality disorder from those without the diagnosis. Strong interrater reliability and reasonable alpha levels were achieved. Although some criteria were successful in identifying patients with and without a diagnosis of antisocial personality disorder, the criteria were generally better at predicting the absence of antisocial personality disorder. PMID- 8488219 TI - Utility of the Hobby WISC-R Split-half Short Form for children and adolescents with severe head injury. AB - This study investigated the utility of the Hobby WISC-R Split-half Short Form in a sample of children and adolescents with severe head injury. Subjects included 30 patients with severe closed-head injuries who were referred for neuropsychological testing as part of their hospitalization in a pediatric rehabilitation center. Subjects ranged in age from 7.5 to 16.2 years and were of the low to middle socioeconomic range. Analyses yielded significant correlations between scores on the standard WISC-R and the Split-half Short Form. Except for the WISC-R Split-half Short Form slightly overestimating scores on Object Assembly, no other score differences were obtained between the two forms. Patterns of strengths and weaknesses were variable for the two forms, with over all agreements ranging from 46% on the Performance subtests to 53.7% on the Verbal subtests. The rate of classification agreement between the standard and short-form formats in assigning a child to one of five traditional IQ categories was 76.7%, with nearly all scores on the short form falling within one standard error of measurement of the standard WISC-R scores. There was a tendency for younger children to show more stability in their classification categories across the two WISC-R forms than older children. Issues related to the use of the WISC-R Split-half Short Form for a severely head-injured pediatric population are discussed. PMID- 8488220 TI - Evaluation of a brief measure of depressive mood for use in a university counseling center. AB - To study the reliability of Set 1 (A, B, C, D) and Set 2 (E, F, G) of the state and trait forms of the Depression Adjective Check Lists in university counseling centers, four independent studies were conducted. Reliability (internal consistency, split-half, and alternate form) and validity (convergent and discriminant) for both sets and both forms were sufficiently high to warrant use for research and clinical purposes. Additional research needs were mentioned. PMID- 8488221 TI - Job stress and satisfaction: international police officers. AB - Scores of 30 police officers on the Occupational Stress Indicator differed from British norms on organisational structure and climate, home and work interface, and relations with others. Officers showed internal control and individual influence. Through managed time and home support, officers coped with stress. Scale scores were intercorrelated. PMID- 8488222 TI - The Patient Satisfaction Interview for partial hospitalization programs. AB - The Patient Satisfaction Interview was developed to assess consumers' satisfaction with four dimensions of partial hospitalization programs: the physical environment, the therapists, the treatment strategies, and the preparation for community autonomy. Content validity of the measure was examined and cross-validated by independent samples of expert raters and patients. The measure was then administered to 30 patients participating in a six-month partial hospitalization program. Analyses showed test dimensions had good internal consistency and test-retest reliability. Six-month stability was good for three of the four scales as well as the over-all test score. Research using the test must examine its utility for description of satisfaction with community-based programs. PMID- 8488223 TI - Motivation of disabled athletes to participate in triathlons. AB - 25 competitors in the Fifth National Triathlon for the Physically Challenged responded to a questionnaire regarding their previous and current exercise and participation in sports. Analysis showed that the majority had been active before the onset of disability and that the encouragement and motivation provided by other physically disabled individuals was the consistent factor in their own initial rehabilitation and subsequent participation in sports. PMID- 8488224 TI - Denigration of a victim in group psychotherapy by violent vs seductive sex offenders. AB - Two psychotherapy groups were set up in a prison treatment program, one for violent sex offenders, the other for sex offenders who were less violent and primarily used seduction to obtain sex. Most of the patients were child molesters. Observations showed that over the course of 10 group psychotherapy sessions, 8 out of 10 violent offenders said denigrating things about their victims vs 2 out of 10 seductive offenders. The significant comparison if supported by cross-validation suggests the value of the distinction of violence vs seduction for sex offenders. PMID- 8488225 TI - A videotape as introduction for cognitive behavioral therapy with depressed inpatients. AB - This paper reports on the development of a videotape "Depression ... the answers" for use in cognitive behavioral therapy with depressed inpatients. 17 patients evaluated the videotape. The described psychoeducational video program was constructed as an introduction for, an opening to, and as a facilitation and clarification of the psychotherapeutic and pharmacological treatments. PMID- 8488226 TI - Effects of explicit time-limits on the initial therapeutic alliance. AB - This study investigated the hypothesis that the setting of explicit time-limits in individual counseling enhances the formation of the therapeutic alliance. Students at a university-based counseling center were randomly assigned to a 5 session, time-limited therapy condition (n = 16) or a time-unlimited therapy condition (n = 15). Contrary to the hypothesis, statistical analyses showed no differences between audiotaped segments from the second and third therapy sessions rated on the Vanderbilt Therapeutic Alliance Scale. PMID- 8488227 TI - Neuroethics vs neurophysiologically and neuropsychologically uninformed influences in child-rearing, education, emerging hunter-gatherers, and artificial intelligence models of the brain. AB - Potentially negative long-term consequences in four areas are emphasized, if specific neuromaturational, neurophysiological, and neuropsychological facts within a neurodevelopmental and ecological context are neglected in normal functional levels of child development and maturational lag of the frontal lobe system in "Attention Deficit Disorder," in education (reading/writing and arithmetic), in assessment of cognitive functioning in hunter-gatherer populations, specifically modified in the service of their survival, and in constructing computer models of the brain, neglecting consciousness and intentionality as criticized recently by Searle. PMID- 8488228 TI - Speaking anxiety, achievement, and crime: a rejoinder to the response by Witherspoon, Long, and Nickell. PMID- 8488229 TI - Fears of normal and retarded children. AB - The developmental features of the fears of 112 nonretarded and 42 retarded children were examined. With development, the fears of nonretarded children became more closely aligned with real sources of threat that involve human agency and less fearful of imaginary things. The retarded children displayed patterns of fears similar to their mental-age peers rather than chronological peers and were more likely to deny being fearful than their nonretarded peers. PMID- 8488230 TI - Locus of control, depression, and anger among African-Americans. AB - Subjects, 98 African-American college students, were given a measure of belief in locus of control, a self-report measure of depression, and three scales from the Buss and Durkee Hostility Inventory. Depression and belief in control by powerful others correlated only for subjects with low scores on Assaultive, Verbal, and Indirect Hostility. The findings, using nonwhite subjects, replicate a previous study in which the racial composition was not indicated. PMID- 8488231 TI - Human response to traumatic events: an integration of counterfactual thinking, hindsight bias, and attribution theory. AB - In documenting cognitive processes underlying persons' reactions to negative events, counterfactual thinking, hindsight bias, and attribution theory focus on distinct, although not unrelated, aspects of human information processing. Counterfactual thinking highlights the cognitive processing undertaken when persons imagine different courses of action that lead to alternative outcomes. Hindsight bias describes the inflated retrospective estimates individuals make regarding event probabilities that come with the advantage of knowledge about outcomes. And attribution theory concerns the affective and behavioral consequences that result from the perceived causes of events. This essay argues that a more comprehensive understanding of the processes underlying human response to traumatic events results from the integration of counterfactual thinking, hindsight bias, and attribution theory into a single model. PMID- 8488232 TI - Prediction of cancer and coronary heart disease mortality by means of a personality inventory: results of a 15-year follow-up study. AB - This paper reports on the 1982-1986 follow-up of two samples of healthy persons first studied in 1972 and followed up in 1982 when mortality and cause of death were established (N = 2,146). Both were related to stress and personality type according to clearly elaborated theories, and results were very much in accordance with theory. The second follow-up was instigated to answer criticisms of the first study and to test whether results would still support the theories involved. The data support the previous results strongly and show that psychosocial data can predict with considerable accuracy mortality and cause of death over 14 years ahead. PMID- 8488233 TI - On the validity of hypotheses derived from the Rorschach: the relationship between shading and anxiety, update 1992. AB - Research on the hypothesis that shading responses on the Rorschach reflect how people deal with their anxiety was reviewed. The research does not lend support to the hypothesis, but serious methodological and conceptual problems with this research make it difficult to assess the meaning of the results of these studies. The nature of needed research is discussed. PMID- 8488234 TI - Anger and sports participation. AB - This study investigated differences between 19 varsity and 20 intramural male football players in trait anger, anger expression, and sports orientation. While varsity athletes reported comparable levels of trait anger, they described significantly less internalized (anger in) and externalized anger (anger out) than intramural athletes. Also, the varsity athletes reported significantly less anger control. Significant differences were also found for competitiveness and goal orientation, but not win orientation, such that the varsity athletes were more competitive and goal-oriented than the intramural athletes. The implications of these findings are discussed in terms of several alternative hypotheses. PMID- 8488235 TI - Hopelessness in adolescent psychiatric inpatients. AB - To study hopelessness in adolescent inpatients, we administered the Beck Hopelessness Scale to 108 inpatients between 12 and 17 years old who were diagnosed with mixed psychiatric disorders. Moderate to severe pessimism about the future was described by 42.6%. A principal components analysis of the correlations among the scale's 20 items was conducted, and three components reflecting rejection of the possibility of a hopeful future, acceptance of the inevitability of a hopeless future, and resignation to the futility of changing the future were identified. These dimensions were comparable to those previously reported for adults, and the usefulness of the scale for evaluating hopelessness in adolescent inpatients was discussed. PMID- 8488236 TI - Adolescent and adult female leaders: comparisons on measures of valued leadership traits and irrational thinking. AB - This study compared the responses of 45 adolescent and 45 adult female leaders on measures of valued leadership traits and irrational thinking. Adolescent leaders value Creativity, while adult leaders view Sense of Purpose an important leadership trait. Adolescent leaders possess significantly more irrational beliefs than adult leaders and tend to endorse those beliefs which reflect high self-expectations, blame proneness, and anxious overconcern about the future. PMID- 8488237 TI - Anxiety, anger, and depression in elderly women. AB - Few epidemiological data are available on affect, such as anxiety, anger, and depression, among elderly persons. Given the increase in the number of relatively older people, epidemiological studies of aging are critically important. The present study was undertaken to elucidate the relationship between age and these affects. Data obtained from 4,302 women participating in a breast cancer screening program, aged over 43 and up to 89 years, showed that correlations for age and anxiety, anger, and depression are generally low, respectively, -.02, .05, and .05. Mean scores for anxiety, anger, and depression over the various age groups are comparatively similar, with some slight age-related trends for anger and depression. The changes in depression (an increase in mean depression scores with increasing age) appeared to be related to the positive association of the self-reported "somatic-depression" with age. PMID- 8488238 TI - Just world beliefs, self-esteem, and attitudes towards homosexuals with AIDS. PMID- 8488239 TI - Anxiety during pregnancy at the time of the Gulf War: comparison of anxiety of Israeli women with normal pregnancies and those with "at-risk" pregnancies. AB - 81 pregnant women were interviewed at the time of the Gulf War. One group was interviewed before the missile attacks began in Israel, and the second group during the period of the attacks. Of the women interviewed, 53 women had "high risk" pregnancies and 28 had normal pregnancies. Despite the hypothesis that women with "at-risk" pregnancies would report a greater rise in anxiety during the missile attacks, it was found that the women with normal pregnancies reported a significantly greater rise in anxiety during missile attacks. It is suggested that the already-stressed "high-risk" group "shut out" the additional anxiety generated by the dangers from the missile attacks. PMID- 8488240 TI - Source of sex education in relation to self-esteem and attitudes towards AIDS precautions among college students. AB - 84 college students responded to Coopersmith's self-esteem scale, Moore and Barling's AIDS Questionnaire, and a background survey querying them as to their sex, race, religion, frequency of church attendance, marital status, college classification, and sources of their sex education. The results indicated that self-esteem scores correlated positively with having received sex education from the parents and negatively with not having received sex education from any of the listed sources. More frequent church attenders were more likely to have received sex education from their parents and to score higher in foreclosure status with regard to attitudes towards AIDS. Persons who scored higher on moratorium status for attitudes towards AIDS were less likely to have received sex education in high school, were more likely not to have received sex education from formal sources, and reported being less likely to use condoms. PMID- 8488241 TI - Pleasure from activities and self-defeating personality. AB - As predicted, people who scored higher on a measure of Self-defeating Personality reported experiencing less pleasure and enjoyment from individual and social activities as well as from personal accomplishments. The results were consistent with the idea that these people maintain a self-image of "loser" by minimizing or discounting positives in their lives. Results were also consistent with prior research showing a positive relationship between self-defeating personality and depressive affect. PMID- 8488242 TI - Mini-Mental State Examination scores: gender and lifetime psychiatric disorders. AB - The Mini-Mental State Examination was taken by 862 subjects from the general population, all born in 1931 and 55 to 57 years of age at the time of the study. These responses were analyzed in detail to obtain normative data for the test, and comparisons were made between the members of the group who had lifetime histories of psychiatric disorder and those who did not. Comprehensive comparisons were also made of the geometric diagram included in the test with the aim of finding nonpathological variations within correct geometric drawings. Apart from providing normative data, findings show a difference in the final score for the sexes, depending on whether Serial 7s are chosen or a word is spelled backwards. The men received a higher score on Serial 7s and the women a higher score on spelling a word backwards. A pretest choice is recommended in that the Serial 7s be selected for men, but omitted for women. Both gender differences and a psychiatric diagnosis correlate with the naming of two digits in a MMS subscore category. PMID- 8488243 TI - Cyclical variations in psychiatric patient-to-staff assaults: preliminary inquiry. AB - This study examined possible cyclical variations in psychiatric patient assaults against staff. A statistically significant greater number of assaults occurred during hotter months. Possible explanations are presented. PMID- 8488244 TI - The evaluation and understanding of pain: clinical and legal/forensic perspectives. AB - The evaluation and proper clinical and legal management of pain clients defy simple remedies. Historically, human pain has challenged the most sophisticated of philosophical, theological, and biomedical explanations. Following an historical overview of pain concepts and treatment, this paper discusses the prevalence in and influence of pain on the modern world. One perspective for viewing multifaceted pain issues is a model developed by John Loeser. This four level model addresses not only tissue damage (Nociception), but also the patient's perception of such damage (Pain), the negative emotional reactions to such perceptions (Suffering), as well as the pain activity stemming from such damage (Pain Behavior)--all issues critical in medical management as well as in personal injury litigation. Several methods for classifying pain are discussed, including acute vs chronic pain, benign vs cancer pain, "real" vs psychogenic pain, and a multiaxial coding schema for pain which encompasses a number of professional disciplines. Clinical pain assessment is then reframed and translated into a legal format more relevant to forensic discovery and case development. PMID- 8488245 TI - Personality subgroups in an inpatient Vietnam veteran treatment program. AB - Millon Clinical Multiaxial Inventory personality profiles of 250 male inpatient Vietnam veterans were examined to locate subgroups within that population. Using a hierarchical cluster analysis to form relatively homogeneous groups, four clusters were identified which accounted for 98% of the population. Three clusters had Millon profiles suggestive of a stress reaction and one cluster had a profile indicative of an antisocial adjustment. As measured by a PTSD subscale of the Minnesota Multiphasic Personality Inventory two clusters are high stress groups and two clusters are lower stress groups. The two Millon personality profiles in the high stress category were an 8-2-1/6 group and a 2-8-1-3 group. The lower stress groups had profiles of /8-2 and 6/8-5. The high stress groups are considered Posttraumatic Stress Disorder groups and the lower stress groups are considered nonPosttraumatic Stress Disorder groups. PMID- 8488246 TI - Psychology of computer use: XVII. Relating self-rated computer experience to computer stress. AB - College students were surveyed using Hudiburg's Computer Technology Hassles Scale and their computer experience. Students with low, moderate, and high computer experience (ns = 67, 77, and 37) appeared to perceive the same interactions as unpleasant. The students selected unpleasant interactions in the same numbers and with the same intensity. PMID- 8488247 TI - Tendency toward controlling behavior in adult children of problem drinkers: an experimental study. AB - Several clinicians have remarked on an obsessive need to control among adult children of alcoholics. In an experimental test of this hypothesis 30 adult children of problem drinkers and 31 control subjects performed a computer simulated coin-tossing task. On half of the trials the outcome of the coin toss was open to control; the outcome was random on the remainder of the trials. The children of problem drinkers and the control group did not differ in their success on the task, but in comparison to control subjects the children of problem drinkers tended to perceive a greater difference between controllable and random trials in the coin-tossing task's openness to control. Of the two groups, the control subjects proved to be more realistic in their assessment of the control they had exercised during the task. These findings are discussed in terms of the theme of control in the lives of the adult children of alcoholics. PMID- 8488248 TI - Joint analysis of site-specific cancer risks for the atomic bomb survivors. AB - Statistical methods are presented for joint analysis of site-specific cancer risks for the atomic bomb survivors. Previous analyses of these data have been made either without regard to cancer type, excluding leukemia, or separately for types or classes of cancers. Clearly, analyses without regard to cancer type are less than satisfactory. The primary advantages of joint, rather than separate, analyses are that: (1) models can be fitted with some parameters common to cancer types and others type-specific; (2) significance tests can be used to compare type-specific risks; and (3) through consideration of more comprehensive models, a clearer understanding may be obtained of the modifying effects of sex, age at exposure, and time since exposure. Joint analysis is straightforward, entailing primarily the incorporation of another factor, cancer type, in the usual cross tabulation of the data for analysis. The use of these methods is illustrated in an analysis of three classes of cancer studied by the National Research Council's BEIR V Committee: digestive, respiratory, and other solid tumors. Based on this analysis, some criticism is made of the BEIR V preferred models. The proposed methods are applicable to models for either relative or absolute risks, and results using both types of models are given. Although some of the gains from joint analysis are apparent from the results here, it will be important to use these methods with a more suitable choice of cancer classes and for cancer incidence data where the diagnoses are more accurate. PMID- 8488249 TI - A model of cell inactivation by alpha-particle internal emitters. AB - Tumor-associated antibodies labeled with 131I and 90Y have been used in the treatment of malignant disease with some success. The use of alpha-particle emitting radionuclides as radiolabels offers potential advantages over beta particle sources. The short range in tissue (< 100 microns) and the high linear energy transfer associated with alpha-particle emitters will result in a more concentrated deposition of energy at the site of radionuclide decay. Thus, if radiolabeled antibodies can be bound to malignant cells specifically, a high differential cell killing can be achieved between the malignant and the normal cells. However, the energy deposition pattern will be strongly dependent upon the configuration of alpha-particle sources relative to the cells, and will consequently impact upon the dose-response characteristics. The purpose of this paper is to study distributions of energy deposition from alpha-particle-emitting radioimmunoconjugates distributed uniformly and nonuniformly around cells through theoretical modeling. Energy deposition spectra for cell nuclei are calculated and used to estimate the survival fraction by a simple biological model. We show that survival curves resulting from nonuniform distributions of alpha-particle emitting radiolabeled antibodies can depart significantly from the classical exponential survival model applied to external alpha-particle beams. The survival curves may have initial slopes much steeper than those produced by a uniform distribution of sources, and they may also depart from linearity. Furthermore, the results of the modelling indicate how survival curves are dependent on the cell and radiolabel spacing. The results from our model compare reasonably well with published experimental data and can be used to facilitate the design and interpretation of radiobiological experiments. PMID- 8488250 TI - Lung hyperpermeability and changes in biochemical constituents in bronchoalveolar lavage fluids following X irradiation of the thorax. AB - Groups of rats were administered different doses of X rays (7.5 and 15 Gy), and the effect on the permeability of their lungs was evaluated during a time frame within which radiation pneumonitis develops. Sham-exposed animals served as controls. End points surveyed included lung weight and increases in the total protein in the lavage fluid. To obtain more detailed information about hyperpermeability and to examine some specific protein changes that occur in the lung's fluid in response to X irradiation, the lavage fluids were subjected to a reverse-phase HPLC technique that resolves 11 fractions quantitatively, including transferrin, albumin, and immunoglobulins derived from blood, as well as eight other protein and nonprotein constituents that appear to be derived from the lung (fractions 1, 2, 6-11). The earliest change following the 7.5-Gy dose was a decrease in fraction 6 at 1 week after exposure. As of Week 5, the lung weight and total protein in the lavage fluid were all normal, while the HPLC analyses revealed significant and equivalent increases in the amount of transferrin, albumin, and immunoglobulins in the lavage fluid; fraction 6 was no longer diminished. At 9 and 13 weeks, hyperpermeability could no longer be detected, while fraction 6 was again decreased at week 13. Fraction 6 was also decreased 1 week after the 15-Gy dose. At 5 weeks, when the weight of the lungs and the total protein in the lavage fluid were elevated, lavage fractions 1, 2, 10, and 11 were all increased, and transferrin, albumin, and immunoglobulins were increased approximately 1500, 1000, and 500%, respectively, and fractions 6 and 9 were decreased. By Week 7, the weight of the lungs returned to control limits, while total protein in the lavage fluid remained elevated. The hyperpermeability was characterized by increases in transferrin and albumin in the lavage fluid, but not immunoglobulins. Fractions 1, 2, 10, and 11 returned to within normal limits, whereas fraction 9 decreased further. Increases in transferrin and albumin were components of a persisting hyperpermeability observed at the last 9-week time point. All other fractions were normal, with the exception of fraction 6, which remained decreased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488251 TI - Radiosensitivity of atomic bomb survivors as determined with a micronucleus assay. AB - If A-bomb survivors include a disproportionately large number of either radioresistant or radiosensitive persons, the surviving population would provide a biased estimate of the true risk of radiogenic cancer. To test this hypothesis, the in vitro X-ray sensitivities of peripheral blood lymphocytes obtained from 937 A-bomb survivors were measured with a cytokinesis-blocking micronucleus assay. Background frequencies (no irradiation in vitro) of micronuclei show a wide distribution. Frequencies in both males and females tend to increase with increasing donor age. Frequencies in females are significantly higher than those in males. Donor age decreases the sensitivity of lymphocytes to in vitro X-ray exposure at a rate of about 0.001 micronuclei per cell per year per gray. There is no effect of donors' sex on in vitro radiation sensitivity. Atomic bomb radiation and cigarette smoking had no significant effect on background and X-ray induced micronuclei frequencies. Thus there is no difference in radiosensitivity of peripheral blood lymphocytes between proximally and distally exposed survivors. PMID- 8488252 TI - Effect of adrenalectomy on the latency of radiation myelopathy in rats. AB - The effect of adrenalectomy on the development of radiation myelopathy was studied. A 1-cm section of cervical cord of adrenalectomized and intact animals was exposed to graded doses (18 to 30 Gy) of gamma rays. The radiation tolerance, the latent period from exposure to paralysis, plasma corticosterone levels at the time of paralysis, and histopathology of the cord were evaluated. Adrenalectomy essentially eliminated endogenous production of corticosterone and significantly shortened the mean latent period between irradiation (24 to 30 Gy) and paralysis by more than 10 weeks. This reduced latent period was not reversed by the administration of the exogenous glucocorticoid, dexamethasone, and corticosterone, although prolonged administration of dexamethasone resulted in the development of Cushingoid features, indicating hypercorticoidism. Histopathological examinations indicated that adrenalectomized paretic animals had multiple hemorrhages in both the gray and the white matter, but less white matter necrosis than normally observed in intact paretic animals irradiated similarly. Possible mechanisms for the shortened latent period in adrenalectomized animals are discussed. PMID- 8488253 TI - Sequence analysis of X-ray-induced mutations occurring in a cDNA of the human hprt gene integrated into mammalian chromosomal DNA. AB - Sequences of 38 independent X-ray-induced mutations in a cDNA of the human hypoxanthine phosphoribosyltransferase (hprt) gene were analyzed after it was integrated into mammalian chromosomes as part of a shuttle vector. There were 15 base substitutions (39%), 9 frameshifts (24%), 11 deletions (29%), and 3 other mutations (8%) of two kinds. Radiation-induced mutations were found throughout the coding region of the gene. Base substitution mutations occurred more often at A:T sites than at G:C sites, and there were more transversions than transitions. Most of the frameshifts and deletions had short direct repeats or a run of several identical bases at the site of the mutation. A slippage misalignment mechanism, suggested previously, can account for the generation of these classes of mutations. The kinds, distribution, and possible mechanism of X-ray-induced mutations were similar to those of spontaneous mutations. PMID- 8488254 TI - Delayed heritable damage and epigenetics in radiation-induced neoplastic transformation of human hybrid cells. AB - The HeLa x skin fibroblast human hybrid cell system has proven to be an excellent model system for quantitative studies of radiation-induced neoplastic transformation in vitro. A unique aspect of this system is the reexpression of a cell surface protein p75/150 with tumorigenicity. The identification of p75/150 as intestinal alkaline phosphatase (IAP) allowed for the recent development of a more simplified, rapid, and sensitive screening method than the previous p75/150 antibody-based staining procedure. The new method directly detects neoplastically transformed, IAP-expressing cells by staining with the alkaline phosphatase chromogenic substrate, Western Blue (WB). Earlier studies with the antibody-based immunoperoxidase assay indicated that, while no foci with tumor-associated antigen (p75-positive) were evident 15 days after irradiation, the number of foci rose quickly and leveled off between Day 19 and Day 23. This late appearance of the IAP-positive foci suggested that the neoplastic transformation process was not an immediate consequence of radiation damage. The mechanism underlying this observation was unknown. The possibility existed that very small foci and/or foci expressing a low level of IAP were being missed at earlier expression times. The increased sensitivity of the WB staining technique has allowed for the reinvestigation of the kinetics of induction of radiation-induced foci in this system. Experiments were performed where parallel groups of transformation flasks were stained at Days 7, 9, 11, 13, 15, 17, 19, and 21 days after irradiation. The data clearly indicate that the radiation induction of IAP-positive foci is indeed delayed in this system with the vast majority of the foci beginning to appear after Day 9 after irradiation. The delay is not the result of a lack of ability to detect small IAP-positive foci since foci with as few as 15 IAP-positive cells were discernible. We have reported previously that under identical experimental conditions both the establishment of plateau phase and the onset of the expression of lethal mutations also occur after Day 9. We therefore propose that radiation-induced neoplastic transformation of HeLa x skin fibroblast hybrid cells is a consequence of the delayed expression of heritable damage under epigenetic control with a resultant loss of tumor-suppressor function. PMID- 8488255 TI - Benign thyroid adenomas among persons X-irradiated in infancy for enlarged thymus glands. AB - Thyroid adenoma incidence in a cohort of 2657 infants given X-ray treatment for a supposedly enlarged thymus gland, along with 4833 unirradiated siblings, has been ascertained for an average of 37 years since irradiation. Estimated thyroid doses ranged from 0.03 to > 8 Gy, with 62% receiving < 0.5 Gy. After excluding 4 adenoma cases with concurrent or previous thyroid cancer, there were 86 cases with pathologically diagnosed thyroid adenomas in the irradiated group and 11 in the sibling controls. The estimated excess relative risk (ERR) was 6.3 per gray (90% CI = 3.7, 11.2). Once the dose group with > or = 6 Gy, which was producing downward curvature in the dose-response function, was removed, the curve was compatible with linearity and the ERR was 7.8 per gray. Thyroid adenoma rates were elevated even at low doses: the lowest dose group (< 0.25 Gy) showed a significant elevation in risk. The relative risk appeared to be constant over time and was comparable for both sexes. Excess adenoma risk was observed in the irradiated group to the maximum follow-up interval of about 50 years. A number of potential risk factors for thyroid adenoma were examined both as risk factors in their own right and as modifiers of the radiogenic risk. Parity and use of hormones in relation to menopause were significantly associated with thyroid adenoma risk in women, while education, Jewish origin, history of hyperthyroidism or hypothyroidism, and family history of cancer were also adenoma risk factors in both sexes. An examination of interactions between possible risk factors and radiation suggested that women with a history of oral contraceptive use or hysterectomy and persons with a family history of cancer may have greater risk (per unit dose) of radiogenic thyroid adenomas than their counterparts. PMID- 8488256 TI - Leukemia and other related hematological disorders among Danish patients exposed to Thorotrast. AB - At least 60 case studies of leukemia among people exposed to chronic low-dose alpha-particle radiation from injections with the radiographic contrast medium Thorotrast and 115 cases from follow-up studies have been described in the literature. In the present study, malignant hematological diseases among 1003 Danish patients injected during 1935-1947 and followed to 1992 accruing 20,433 person-years were assessed and available histopathological specimens revised. The mean cumulative bone marrow alpha-particle radiation dose (1.34 Gy) was estimated from records of the amount of Thorotrast injected (mean 18.7 ml). Sixteen cases of acute myelogenous leukemia (AML) and seven cases of myelodysplastic syndrome (MDS) were diagnosed 8-40 years after injection, the cumulative frequency reaching 7.6%. No significant relationship was seen between the cumulative frequency of AML + MDS and the age at injection, gender, or amount of Thorotrast injected, but a multivariate analysis described data best by a model with the bone marrow dose and the power of the attained age. The risk estimate for AML + MDS was 173 cases/10(4) persons per Gy. If also considering cases of acute lymphocytic leukemia (1), chronic myelogenous leukemia (3), non-Hodgkins lymphoma (4), and multiple myeloma (2), the risk estimate became 248 cases/10(4) persons per Gy. It is suggested that RBE of alpha particles from thorium may be lower than 20. PMID- 8488257 TI - Zero tumor incidence in mice after repeated lifetime exposures to 0.5 Gy of beta radiation. AB - A final series of experiments on tumor induction by repeating 90Sr-90Y beta irradiation of the back of ICR mice three times weekly throughout the life span showed no tumor incidence with repeated doses of 0.5 Gy per exposure. The whole dose-response relationship for repeated irradiation with 0.5 to 11.8 Gy per exposure, summarized along with data obtained previously, showed a unique nonlinear dose response with saturation of tumor incidence at doses of over 2.5 Gy per exposure and a threshold-like value around 1.5 Gy per exposure. PMID- 8488258 TI - Radiation-induced proliferation in contralateral unirradiated kidneys. AB - Following irradiation of a single kidney in mice, the weights and labeling indices in the irradiated and contralateral unirradiated kidneys were measured. Three to 12 months after irradiation we found that the proliferation of proximal tubule cells was increased not only in the irradiated kidney but also in the contralateral unirradiated kidney. The labeling index in the contralateral unirradiated kidney did not increase in the first month after irradiation but it did in the irradiated kidney. Contralateral kidney weight increased as the weight of the irradiated kidney decreased. We suggest that cell proliferation in the contralateral kidney was probably induced through a humoral growth factor beginning 3 months after irradiation. We postulate that induced cell proliferation in the irradiated kidney is a result of a local factor at 1 month and of local and humoral factors at later times. PMID- 8488259 TI - Low-dose-rate irradiation of rat embryo cells containing the Ha-ras oncogene. AB - Rat embryo cells and derived transfectants containing the Ha-ras oncogenes were irradiated with 60Co gamma rays at dose rates of 0.72, 0.066, 0.035, and 0.018 Gy/min. The measured dose response of cell survival shows that the oncogene containing cells exhibit higher survival levels at all doses than the parental cells at every dose rate. The response of the cells containing the ras oncogene also became dose-rate independent at a higher dose rate, perhaps indicative of a greater repair capability relative to that of the primary cells. PMID- 8488260 TI - [Genome mapping of human chromosome 11--construction of cytogenetic map]. PMID- 8488261 TI - [Physical mapping of human chromosome 21--construction of a NotI restriction map by linking clone mapping]. PMID- 8488262 TI - [Analysis of chromosome 21--construction of STS map and its application for contig map construction]. PMID- 8488263 TI - [Human genome analysis using chromosome sorting]. PMID- 8488264 TI - [Mapping the human Y chromosome]. PMID- 8488265 TI - [Analysis of oncogenes and tumor suppressor genes]. PMID- 8488266 TI - [Abnormal gene in Huntington's disease]. PMID- 8488267 TI - [Genetic studies in the neuropsychiatric disorders]. PMID- 8488268 TI - [Cloning of the genes underlying neurological diseases--chromosome dissection and SUP-PCR]. PMID- 8488269 TI - [Molecular genetic approach for positional cloning of X-chromosome-linked diseases]. PMID- 8488270 TI - [Genetic analysis of hypertrophic cardiomyopathy]. PMID- 8488271 TI - [Organization of the human T-cell receptor genes and its involvement in chromosome translocations in T-cell malignancy]. PMID- 8488272 TI - [Gene organization of HLA region]. PMID- 8488273 TI - [The centromere of human chromosome]. PMID- 8488274 TI - [Organization of the human immunoglobulin heavy chain variable regions genes]. PMID- 8488275 TI - [An equalized cDNA library and its application]. PMID- 8488276 TI - [Fission yeast cDNA project]. PMID- 8488277 TI - [Human genome analysis by large scale DNA sequencing]. PMID- 8488278 TI - [The large scale cDNA database and the analysis system--cDNA binder]. PMID- 8488279 TI - [Homo.protein cDNA bank--from molecular taxonomy to molecular ecology]. PMID- 8488280 TI - [cDNA project of embryonal carcinoma cells]. PMID- 8488281 TI - [Toward the construction of a full length cDNA library]. PMID- 8488282 TI - [cDNA subtraction]. PMID- 8488283 TI - [Exploration of new genes in the nervous system]. PMID- 8488284 TI - [Approach to protein catalog]. PMID- 8488285 TI - [Chemical cleavage of long chain DNA--molecular design for artificial restriction enzyme]. PMID- 8488286 TI - [Separation of large DNAs--inhomogeneous field gel electrophoresis]. PMID- 8488287 TI - [Separation of large DNAs--large DNA dynamics in gel]. PMID- 8488288 TI - [Triple helix DNA and genome analysis]. PMID- 8488289 TI - [Human genome mapping by direct R-banding fluorescence in situ hybridization]. PMID- 8488290 TI - [Methodology of gene mapping]. PMID- 8488291 TI - [Use of microcell-hybrid for genomic analyses]. PMID- 8488292 TI - [Collection and analysis of polymorphic repetitive sequences]. PMID- 8488293 TI - [Dual-laser chromosome sorting]. PMID- 8488294 TI - [Screening of YAC library]. PMID- 8488295 TI - [Stabilization of the YAC clone]. PMID- 8488296 TI - [P1 phage vector]. PMID- 8488297 TI - [Structural analysis of giant DNA by a defined in vitro DNA packaging system of T3 phage]. PMID- 8488298 TI - [Exon trapping and its application]. PMID- 8488299 TI - [Automated DNA sequencer in genome analysis]. PMID- 8488300 TI - [Construction of an automated system of human genome analysis (HUGA-I)]. PMID- 8488301 TI - [Sequencing by oligonucleotide hybridization]. PMID- 8488302 TI - [Genomic analysis of Escherichia coli K-12]. PMID- 8488303 TI - [Sequencing project of Bacillus subtilis genome]. PMID- 8488304 TI - [Genome mapping of Schizosaccharomyces pombe]. PMID- 8488305 TI - [Genome analysis of the nematode C. elegans]. PMID- 8488306 TI - [Genome analysis of mice]. PMID- 8488307 TI - Holism, holes, and wholes. PMID- 8488309 TI - Health consequences of loneliness in adolescents. AB - The purpose of this study was to test a causal model developed from a theoretical formulation of the health consequences of loneliness in adolescents. The sample consisted of 325 adolescents, ages 12 to 21. Data were obtained in classroom settings on the variables of age, gender, and loneliness on one testing date; and on the variables of introspectiveness, symptom patterns, and perceived health status on another testing date 1 week later. The causal model was tested via the LISREL 7 program. By all indicators used in this study, there was a very good fit of the overidentified model with the data, the causal relationships predicted in the model were correctly specified, and modification of the model was not indicated. The results indicated that loneliness contributed to introspectiveness, that both loneliness and introspectiveness contributed to the reporting of symptom patterns, and that all of the aforementioned variables contributed directly and/or indirectly to a less positive perception of health status among adolescents. A vast majority of the direct and indirect effects of age and gender predicted on other variables in the model were supported. PMID- 8488308 TI - Outcomes of specialized and traditional AIDS counseling programs for impoverished women of color. AB - The efficacy and differential effects of specialized (S) and traditional (T) AIDS education programs on cognitive, behavioral, and psychological outcomes were investigated. The sample consisted of 858 impoverished African-American and Latina women (S = 448, T = 410). At baseline, women in the traditional group reported significantly higher distress, greater knowledge of AIDS, and less problem-focused coping. Significant improvements over the 2-week intervention interval were found for participants of both AIDS education programs for appraisal of threat, concerns, knowledge, and attitudes about AIDS, emotion focused coping, number of sexual partners, IV and non-IV drug use, depression, and distress. However, multivariate analysis indicated that the traditional group had slightly better posttest scores on concerns, emotion-focused coping, knowledge of AIDS, and number of partners than the specialized group. The specialized group reported greater use of problem-focused coping. These differences do not detract from the substantial improvement found for both groups, but they do reinforce the conclusion that the specialized program was not more effective than its standard counterpart. PMID- 8488310 TI - Integration of biological and nursing sciences: a 10-year plan to enhance research and training. AB - A proposed multiyear plan of funding mechanisms by the National Center for Nursing Research (NCNR) to increase the use of biological theory and measurements in nursing research has been developed for both research training and research programs. The objectives of the research training programs are (a) to develop a cadre of nurse scientists with solid research training in the biological sciences, (b) to upgrade to state-of-the-art biological research for mid-career nurse scientists, and (c) to ensure adequate highly trained biological-nurse manpower will be available to accomplish the nation's nursing research agenda. The objectives of the research programs are (a) to stimulate nurse scientists to undertake novel, innovative research using state-of-the-art biological technology, (b) to link the behavioral and biological underpinnings of nursing science in specified areas of biomedical clinical research, and (c) to ensure that, in the coming decade, nursing science and behavioral research will be inextricably interwoven with biological research. The research training programs include: targeted predoctoral-postdoctoral transitional training, targeted predoctoral or postdoctoral fellowships, training awards for existing institutional training grants in other disciplines, mid-career awards, the Nurse Scientist award, and institutional training grants for biological nursing. The research programs include: small grants programs, augmentation of existing projects in other Institutes, Requests For Applications (RFA) in biobehavioral nursing, cluster studies, and clinical trials. PMID- 8488312 TI - Predictors of partner relationships during pregnancy and infancy. AB - The partner relationship of 153 women hospitalized for a high-risk pregnancy, 75 of their partners, 218 women who experienced a low-risk pregnancy and 147 of their partners was studied to determine risk-status or gender differences at pregnancy, the postpartal hospitalization, 1, 4, and 8 months following birth. A theoretical causal model predicting partner relationships was tested, followed by model respecification to derive the best explanatory model for each group. No differences were observed between low- and high-risk mothers' partner relationship; however, high-risk fathers scored lower than low-risk fathers. Partner relationships for all groups were significantly higher during pregnancy and at birth than at 4 and 8 months after birth. Respecified models explained from 26% to 63% of the variance in partner relationship during pregnancy, and from 31% to 52% at 8 months after birth. PMID- 8488311 TI - Maternal employment, family functioning, and preterm infant development at 9 and 12 months. AB - The purpose of this study was to investigate the effects of maternal employment on child development and family functioning for families with preterm infants. Data were collected in the family's home (N = 67) when the infant was 3, 9, and 12 months of age. Maternal employment at 3 months had little effect on 9- and 12 month child mental or psychomotor development or on family cohesion, adaptability, or satisfaction. Maternal employment attitude/behavior consistency was a significant predictor of psychomotor development. Choice in the employment decision at 3 months was positively related to both mental and psychomotor development at 9 and 12 months for nonemployed mothers. PMID- 8488313 TI - Everyday indicators of impaired cognition: development of a new screening scale. AB - Development of the Everyday Indicators of Impaired Cognition (EIIC) Scale to assess nursing home residents for performance errors in four domains of cognitive functioning is reported. The EIIC had strong content validity, with indices ranging from .7 to 1.0. Factor analyses of data from two independent samples (N = 198, N = 107) confirmed four factors: abstract thinking, judgement, language, and spatial skills. Cronbach's alpha for subscales ranged from .67 to .92; test retest reliabilities ranged from .49 to .80 with higher reliabilities occurring when time of retest matched time of original testing. Overall EIIC scores correlated to the short Memory-Orientation-Concentration (MOC) test and the Mini Mental Status Examination (MMSE) at values supporting convergent validity (r = .67 and -.74, respectively). Evidence for divergent validity is a small, negative, nonsignificant correlations (r = -.15, -.18) of the EIIC at Times 1 and 2 to the Bradburn Affect Balance Scale. PMID- 8488314 TI - The erosion of nursing resources: employee withdrawal behaviors. AB - A 5-year retrospective cohort study of 404 nurses hired during a 2-year period in five hospitals was conducted in order to explore withdrawal behavior exhibited by 76% of them. Three withdrawal behaviors were examined and compared: turnover, absenteeism, and systematic reduction in participation (reduced work schedules). In two separate regressions, systematic reduction in participation (SRP) and turnover were each regressed on absenteeism, after controlling for six organizational and demographic variables. The relationship between absenteeism and each of the other two behaviors was significant, but opposite in effect. Systematic reduction in participation was found to be an important source of nursing resource loss in some, but not all, hospitals. PMID- 8488315 TI - Nursing intervention studies require outcome measures that are sensitive to change: Part Two. AB - Ohis article is the second and concluding part of a discussion of the importance of sensitivity to change in selecting an outcome measure for a study evaluating a nursing intervention. In Part One of the discussion, (Stewart & Archbold, 1992) the relative lack of attention to measurement sensitivity in the nursing and measurement literature was described. Three factors to consider in selecting an outcome measure for an intervention study were reviewed: the conceptual link between the intervention and the outcome variable, the extent to which the outcome variable is amenable to change, and content validity. In Part Two, four additional factors are discussed: construct validity, distribution of scores on the outcome measure, reliability, and correlational stability over time. PMID- 8488316 TI - [Angiotensin-converting enzyme inhibitors in the treatment of heart failure: toward a change in the natural history of the disease]. PMID- 8488317 TI - [The incidence of arrhythmias in young persons without demonstrable heart disease: a 24-hour Holter study in 100 medical students]. AB - A Holter monitorization study was performed in 100 voluntary university students (64 men and 36 women). The mean age was 23.6 years and organic heart disease was ruled out in all cases. Data were analysed in different subgroups including the practice of physical activity and subjects smokers or alcohol consumers. The maximum heart rate (HR) achieved during the wake period was 138.3 +/- 20.43 beat/m. Minimum daytime heart rate was 61.42 +/- 10.32 beat/m and it was below 60 beat/m in 41 subjects. During the nighttime period, the maximum heart rate achieved by the group was 89.34 +/- 11.31 beat/m. Minimum nighttime heart rate was 45.82 +/- 6.35 beat/m. Maximum heart rate in men was 134.3 +/- 21.35 beat/m, while in women was 145.42 +/- 16.36 beat/m. Eighty students presented one or more arrhythmias, among them 28 women and 52 men (p = NS): 92% in sportsmen and women groups as compared with 79% in the non sports practicers, 90% of alcohol consumers and 82% between subjects who smoked and drank, compared with 63% in the non drinkers (p < 0.006). 48% of the subjects presented one or more supraventricular arrhythmias during the daytime or during the nighttime (p = NS). Ventricular rhythm disturbances were found in 20 subjects. There was only one case who had a non sustained ventricular tachycardia of 4 complexes. These disturbances were not increased by practising sport nor by toxic habits. In 15 cases we found sinoatrial block, with a male predominance. Five subjects presented some type of atrioventricular block, 4 of which were alcohol and tobacco consumers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488318 TI - [The detection of acute myocardial infarct without a Q wave; indium-111-labelled antimyosin antibodies versus technetium-99m-labelled radiophosphates]. AB - In order to ascertain whether antimyosin myocardial imaging is superior to the more conventional cardiac radiophosphate scanning for the diagnosis of non Q wave acute myocardial infarction (AMI), we conducted a comparative study with the contemporary use of both tracers. Forty eight patients admitted to the coronary care unit of our centre because of non Q AMI, were included. Between two and seven days after onset, cardiac scintigraphy was performed both using 99mTc labelled diphosphonic-propane-dicarboxylic acid (99mTc-DPD) and 111indium labelled antimyosin (111In-AAM). In addition to planar imaging, tomoscintigraphy (SPECT) with 99mTc-DPD was obtained in 12 patients. 99mTc-DPD imaging was positive for AMI in 44% of the cases, while 111In-AAM in 52% (NS). In most positive cases (more than 85%) myocardial necrosis was localised in the posterolateral wall. In the subgroup of SPECT imaged patients, the percentage of positive findings was the same as the percentage using planar 111In-AAM imaging (58%). We conclude that the apparent efficacy of antimyosin for the diagnosis of non Q AMI is similar to that of 99mTc-DPD imaging. We feel that owing to its higher cost, such procedure should be saved for those cases were standard 99mTc DPD imaging fails to detect the infarcted myocardium. PMID- 8488319 TI - [The role of Doppler of effort in the indications for percutaneous valvuloplasty and/or mitral surgery in patients with a preserved functional class]. AB - We have evaluated in this study the role of exercise Doppler echocardiography to establish the clinical indication of invasive procedures in patients with mitral stenosis and preserved functional class. Thirty-tree patients, mean age 45 +/- 9 years, underwent 35 exercise Doppler studies by supine bicycle ergometry with a 2 MHz nonimaging continuous wave Doppler probe. Sixteen patients were in N.Y.H.A. class I and 19 in class II. Peak and mean mitral gradient were obtained at rest, during, at maximal exercise and at recovery period, averaging at least 5 cardiac cycles. The data of 16 patients with mitral area at rest < 1.2 cm2 (group I) were compared with the data of 19 patients with mitral area at rest > 1.1 cm2 (group II). The mean gradient (mmHg) in the group I compared with respect group II was significantly higher at rest (9.5 +/- 3 vs 6 +/- 3, p < 0.01), step 1 (21 +/- 5 vs 14 +/- 6, p < 0.001), step 2 (26.4 +/- 5 vs 17.9 +/- 6, p < 0.001), step 3 (26.5 +/- 4 vs 20.7 +/- 6, p < 0.01), step 4 (29.8 +/- 5 vs 23.8 +/- 4, p < 0.05) and peak exercise (31.4 +/- 4 vs 21.9 +/- 6, p < 0.001). The functional capacity in mets was similar in both groups (6.7 +/- 1 vs 7.2 +/- 2, p = NS). Three patients of group I (15.7%) showed the same increase of gradient as group I. We conclude that exercise Doppler echocardiography allow identification of the haemodynamic severity of patients with mitral stenosis and preserved functional class. This technique could be a good tool in clinical indication of invasive procedures in these patients. PMID- 8488320 TI - [The transmitral gradient of effort: old concepts, new technologies]. PMID- 8488321 TI - [The nonpharmacological treatment of tachyarrhythmias in 23 children and adolescents]. AB - We comment the results with non pharmacological treatment in 23 patients (mean age 11 +/- 4 years) with multiple episodes of palpitations, most of them required intravenous drugs for interrupting it. Twenty-eight procedures were performed, 17 catheter ablation and 11 surgical interventions. The energy source employed for fulguration until 1990 was DC and since 1991 radiofrequency. The best results with catheter ablation were obtained with accessory pathways. Interruption was achieved in all patients after a mean of 1.2 sessions per patient, but it was definitive in only 72%. Most of the patients (81%) remained asymptomatic without antiarrhythmic drugs. Nine patients with accessory pathways underwent surgery interruption, it was achieved in all; only one patient had arrhythmia recurrence, due to a second pathway in a different localization. We could not ablate a ectopic atrial tachycardia, that underwent surgery. There was only one indication for surgery in a patient with ventricular tachycardia. Catheter ablation does not present technical problem in children and teenagers, different from adults. The presented results lead us to suppose that the indications for non pharmacological treatment in the young will become more common. PMID- 8488322 TI - [Peripheral vascular reflexes during ventricular overdriving and cardiac ischemia. An experimental study]. AB - The aim of this paper is to analyze the behaviour of the muscular arteries during ventricular tachycardia in normal and in ischemic hearts. In 19/30 anaesthetized dogs in which a resistance vessel (gracilis muscle artery) was isolated (while innervation and venous backflow remained intact), we performed transient (20 min) coronary artery occlusions and ventricular overdriving (30 sec). A systolic left ventricular pressure decrease (144.2 +/- 18.2 mmHg vs 114 +/- 16.1) (p < 0.001) was produced with the coronary circumflex obstruction. Changes in the end diastolic left ventricular pressure and muscular artery pressure were not significant. A new systolic left ventricular pressure decrease (114 +/- 16.1 mmHg vs 64.8 +/- 27) (p < 0.001) was induced when the ventricular overdriving (272.2 +/- 46.1 bpm) was added to the coronary circumflex obstruction. The end-diastolic left ventricular pressure increased (6.8 +/- 10.1 mmHg vs 18.3 +/- 4.8) (p < 0.001) and the muscular artery pressure increased (121 +/- 27.3 mmHg vs 158.1 +/- 21.3) (p < 0.01) in these circumstances. When the ventricular overdriving (275 +/ 70.7 bpm) was added to the left descendent anterior coronary occlusion a significative decrease of left systolic ventricular pressure (141 +/- 23 mmHg vs 84.4 +/- 28.4) (p < 0.01) and an increase of the muscular artery pressure (124.3 +/- 25 mmHg vs 149 +/- 25.1) (p < 0.01) was produced. Ventricular overdriving induced hypotension produced an isolated muscular artery response with clear vasoconstrictor predominance, which indicates that there is a natural compensatory capacity with predominance of efferent sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488323 TI - [Myocardial contusion with and without coronary artery involvement]. AB - We present the first case of myocardial contusion secondary to blunt chest trauma with injury in two different areas, with and without coronary lesions. The akinesis of the anterolateral wall was secondary to the obstruction of the left anterior descending coronary artery and the severe hypokinesis of the posterior wall, without lesion of the right coronary artery, was probably related with the compression between the sternum and vertebral column. PMID- 8488324 TI - [Biventricular rhabdomyoma or a case of spontaneous regression. A two-dimensional echocardiographic study]. AB - We present the case of an infant diagnosed by prenatal echocardiography as having a biventricular rhabdomyoma which was confirmed after birth. In the series of two dimensional echocardiographies this tumor was seen to decrease in size until its complete disappearance. PMID- 8488325 TI - [Exercise-induced atrioventricular block]. AB - Exercise-induced atrioventricular block in patients with normal atrioventricular conduction at rest is uncommon. Electrophysiologic studies have documented block distal to the atrioventricular node in these patients. Implantation of a permanent pacemaker is recommended because of a high incidence of subsequent symptomatic block. We report three symptomatic patients with exercise-induced atrioventricular block. Two patients showed a bundle branch block in the baseline electrocardiogram, suggesting a distal location of the block. In the remainder, with a normal QRS, the electrophysiologic study revealed AV block within the His bundle in response to atrial pacing. PMID- 8488326 TI - [Embolism due to cholesterol crystals]. AB - We present a case of cholesterol crystal embolization confirmed histologically by skin biopsy and by the presence of a yellowish microemboli with a refringent look lodged inside a retinal arterioles. The presence of a typical clinic case history, together concurrent risk factor (coronarography, implantation of stent and anticoagulation) supported the diagnostic suspicion. Although it is a serious illness, often with a fatal evolution, the patient has followed a favourable clinic course. PMID- 8488327 TI - [The possible damages from cosmetic abuse]. PMID- 8488328 TI - [The new education of the physician in the Italian university. A low percentage of students abandoning their medical studies who attend the degree course in medicine and surgery under the new regulations]. PMID- 8488329 TI - [Angiotensin II stimulates endothelin-1 release from human endothelial cells]. AB - Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide isolated from the culture supernatant of porcine aortic endothelial cells. This 21 amino acid residue peptide has potent vasoconstrictive properties in vitro and in vivo. ET-1 action involves phosphatidylinositol turnover, calcium mobilization and protein kinase C activation. Endothelial cells have distinct receptors for different operating through hydrosoluble hormones. The aim of this study was to investigate on a possible role of angiotensin II (ANG II) to modulate the release ET-1 from human endothelial cells in vitro. These data revealed a time- and a dose-dependent increase of ET-1 production in response to ANG II. This mechanism may have important pathophysiological implications in vivo. In fact, a double mechanism of secretion of ET-1 from endothelial cells could exist: one active in a physiological condition and an other in response to a vasoconstrictor stimuli (as well as ANG II). Furthermore, these results may suggest an additional favourable effect of ACE-inhibition in human hypertension therapy. PMID- 8488330 TI - [Ischemic stroke and transient ischemic attacks: a case-control study of the risk factors in elderly hospitalized patients]. AB - We have evaluated in a case-control study the association of the main risk factors with cerebrovascular ischemic accidents in elderly patients. Two hundred and twenty patients aged 65 year or more (average age 77.3 +/- 7.3 yr, 93 males and 127 females) admitted to our Division for stroke (122) or transient ischemic attacks (TIA) (98) were enrolled: 220 hospitalized patients, age and sex-matched, without actual or previous cardiovascular clinical manifestations were the control group. Advanced senile decay, hepatic or renale failure and malignancies were considered exclusion criteria for both groups. The following risk factors have been considered: family history, obesity, cigarette smoking, diabetes, hypercholesterolemia, hypertriglyceridemia, atrial fibrillation, left ventricular hypertrophy, and related continuous variables. After logistic multiple regression analysis, atrial fibrillation, hypertension and blood cholesterol concentration above 240 mg/dl were significantly and independently associated with stroke, while only hypertension and hypercholesterolemia were associated with TIA. The unexpected finding of a significant association between hypercholesterolemia and cerebrovascular ischemia seems attributable to the choice of hospitalized patients as control group. These results indicate that hypertension and atrial fibrillation are independently associated with ischemic stroke even in advanced age. PMID- 8488331 TI - [Community-acquired bronchopneumonias in the elderly. The cost-benefit ratio in some plans of antibiotic therapy]. AB - Community-acquired pneumonias represent the first cause of mortality due to a infectious disease, and determine more than 500,000 hospitalizations per year in the USA: moreover, they are the terminal event in many geriatric patients. Although the etiological microbial agents responsible for the majority of such pneumonias, Haemophilus influenzae and Streptococcus pneumoniae, are still sensitive to traditional antibiotics, as ampicillin, many doctors treat community acquired pneumonias with more recent and expensive antibiotics, as the third generation cephalosporins or other beta-lactamines, so enhancing the cost of the treatments, without a known, real advantage with respect to the older therapies. In this study, to evaluate whether the use of the latter antibiotics improves the outcome of community acquired pneumonias of the elderly with respect to the traditional therapy with ampicillin, we studied 123 hospitalized patients older than 65 years, affected by community-acquired pneumonia, simple or complicated. We also evaluated the cost/benefit ratio of every single treatment. Our data demonstrate that the recent antibiotics do not influence the outcome of the disease of the elderly: in particular, they do not affect the duration of the hospitalization, do not have a lower incidence of side effects, do not show a better efficacy versus ampicillin. The cost of the treatment with ampicillin is about one third of the cost of a third-generation cephalosporin treatment. We conclude that the treatment of choice for community acquired pneumonias of the elderly is ampicillin; only in few cases, as in nosocomial or in nursing homes pneumonias, third-generation cephalosporins or other antibiotics are necessary. PMID- 8488332 TI - [Rectal neoplasms]. PMID- 8488333 TI - [New horizons in medicine. Chaos and its laws]. AB - We have synthesized the fundamentals that modern technology offers in all areas of research, especially in the field of biomedicine. The theory of systems, cybernetics, synergetics, boolean algebra, communication science (according to modern laws of signal transmission and translation), the solution of non-linear equations by computer science, applied principles of reduction in biological survey, fractal analysis as a representation of dynamic, chaotic, non-linear systems, defined attractors as conditioning elements of biologic function, are just a few of the many instruments that modern science offers as a revolutionary approach to research programming. Borrowing the laws of mathematics, we have defined the fundamental characteristics of linear and non-linear homeostatic systems along with the concept of predictable behavior of a system as a function of its complex structure. Lastly, we have documented, based on personal research and recent findings in biomathematics, and despite current and strong opposition, how the functional death of any dynamic system is identified by the system's absolute state of equilibrium. The operative errors at times caused by different stimuli acting on specific organs and apparatus, are interpreted not as an index of altered function but as an expression of a chaotic response of the deterministic type and therefore an indication of the system's adaptability to the specific functional requirements in that precise moment. PMID- 8488334 TI - [The medical treatment of primary hyperparathyroidism]. AB - The first-choice treatment of primary hyperparathyroidism is surgical removal of abnormal parathyroid gland(s) and the medical management is usually reserved only to control severe hypercalcemia. However, asymptomatic primary hyperparathyroidism with mild hypercalcemia and renal and bone status close to normal is now the more common picture of the disease and in this situation conservative management can be considered, because many of those patients may have a prolonged benign course. Management guidelines are therefore devised to minimize the risk for deterioration of renal, skeletal or gastrointestinal complications of hyperparathyroidism. General medical management includes recommendation to avoid dehydration, immobilization or excessive dietary calcium intake and therapy with thiazides; intravenous infusion with isotonic saline combined to furosemide or etacrinic acid are recommended to treat acute or threatening hypercalcemia. Many other drugs as phosphate, mithramycin, gallium nitrate and calcitonin have been reported to be useful in reversing hypercalcemia but their transient effects, toxicity and side effects limit their clinical use. The bisphosphonates, a new class of bone resorption inhibitors, have been shown to be particularly safe so they result especially effective on controlling acute hypercalcemia and on preventing "hungry bone" disease. However, their effect is not sustained because the serum calcium tends to return toward pretreatment levels despite continued therapy; therefore their consistent beneficial effect on long-term treatment seems unlike. PMID- 8488335 TI - [The diagnosis and therapy of hyperprolactinemia]. AB - Hyperprolactinaemia is the most common result of pituitary dysfunction and is characterized by alteration on the reproductive function. After a review of the hypothalamic control mechanisms and of the local paracrine and autocrine factors regulating prolactin secretion, the most common physiological, pharmacological and pathological causes of hyperprolactinaemia are described. The clinical pictures of hyperprolactinaemia in man and woman are then summarized. The diagnostic protocol used in this Institute is then described: confirmation of the existence and entity of hyperprolactinaemia by means of a prolactin profile; exclusion of pharmacological or extra pituitary causes (cirrhosis, primitive hypothyroidism, chronic renal failure, etc.); neuro-radiological evaluation of the sella region, by means of standard X-ray, computer tomography scan, nuclear magnetic resonance. The drugs commonly used in medical treatment of hyperprolactinaemia such as a bromocriptine, other-derived compounds and then recent CV 205-502, and the surgical approaches (trans-sphenoidal and transcranial routes) are reported. The indication of medical or surgical treatment and the relevance of radiotherapy are finally considered. PMID- 8488336 TI - [Technological innovations in a medical library]. PMID- 8488337 TI - The role of lipid peroxidation and calcium in galactosamine induced toxicity in the rat liver. AB - Liver homogenate and subcellular fractional levels of lipid peroxides, homogenate glutathione (GSH) and calcium contents and hepatic plasma membrane Ca(2+)-ATPase activity were determined in rats, 12, 18, 24 and 48 hours after treatment with a single dose of 1 g/kg galactosamine. Lipid peroxides and calcium levels in liver homogenate and subcellular fractions were found to increase, but hepatic GSH content and Ca(2+)-ATPase activity were observed to decrease reversibly. PMID- 8488338 TI - Effects of procainamide, tocainide and phenytoin on guinea pig cardiac mitochondrial ATPase activity. AB - The effects of three class I antiarrhythmic drugs procainamide, tocainide and phenytoin on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. Tocainide inhibited the ATPase activity in the range of 1.0 nM-500 mM, exhibiting IC20 and IC50 values of 9.4 +/- 0.7 microM and 5.2 +/- 0.4 mM, while procainamide exhibited significant (p < 0.05) inhibitory effect only at concentrations above 1.0 mM with IC20 and IC50 values of 35.4 +/- 2.7 mM and 90.8 +/- 3.7 mM, respectively. On the other hand, phenytoin inhibited the enzyme by 17% and 8% at 1.0 nM and 1.0 microM respectively, while it stimulated it at higher concentrations, thereby increasing its activity by 10%, 57% and 227% at 10, 100, 1000 microM, respectively. The inhibitory actions of these drugs are probably related to their lipophilicity and membrane stabilizing activity, while the stimulatory effect of phenytoin suggests some specific interaction with some component(s) of the oxidative phosphorylation or respiratory chain. PMID- 8488339 TI - Anti-Candida activity of the anti-cancer drug tamoxifen. AB - Earlier workers found that tamoxifen, a drug widely used to treat breast cancer, can exert a marked antifungal action against the non-pathogenic yeast Saccharomyces cerevisiae. In this report, the earlier observation has been extended to Candida albicans, the most important of the opportunistic fungal pathogens. Experiments in which antifungal effect against logarithmic phase cells was monitored by viable count as a function of drug exposure time clearly showed that tamoxifen is highly fungicidal at 2.0 x 10(-5) M, moderately and transiently fungicidal at 1.0 x 10(-5) M, but only very weakly fungistatic at 5.0 x 10(-6) M. PMID- 8488340 TI - Interaction between beta blockers and epinephrine on hemodynamics of spontaneously hypertensive rats. AB - Hypertensive patients treated with nonselective beta adrenergic blocking agents may show remarkable hemodynamic changes with administration of epinephrine clinically. We have attempted to investigate the effects of the interaction between beta blockers (a nonselective beta blocker, pindolol, and a cardioselective beta blocker, acebutolol) and a solution of 2% lidocaine containing 1:80,000 epinephrine on the hemodynamics of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), as compared with the normotensive rats. The blood pressures (systolic and diastolic) and heart rate were measured indirectly by the photoplethysmographic tail cuff method. All drugs were administered intraperitoneally. We found that: (1) epinephrine with pindolol or acebutolol pretreatment did not cause significant hemodynamic changes in WKY; (2) in SHR, epinephrine in combination with pindolol induced remarkable hemodynamic changes (in particular, increase in diastolic blood pressure), which were prevented by phentolamine pretreatment, whereas epinephrine with acebutolol pretreatment induced no significant hemodynamic changes in these animals; (3) epinephrine in combination with pindolol caused pulmonary congestion or edema in SHR; this was confirmed by both quantitative analysis and histological investigations. These results suggest that pindolol blocked both beta 1 and beta 2 receptors, and therefore, this resulted in exaggerated alpha effects of epinephrine, a remarkable systemic vasoconstriction, and pulmonary congestion. In a clinical setting, great caution should be paid to the hypertensive patients, who are being treated with nonselective beta blockers, if epinephrine-containing local anesthetics are administered. PMID- 8488341 TI - Recovery of decreased antibody production by ceruloplasmin in the macular mutant mouse. AB - The macular mutant mouse is a murine model of Menkes' kinky hair disease, characterized by a serum copper and ceruloplasmin deficiency. The hemizygote (ml/y) had a decreased antibody response to sheep red blood cells (SRBC). 1) In vivo; the administration of ceruloplasmin recovered antibody production in ml/y mice, but, had no effect on that of normal mice (+/y). The administration of heat treated ceruloplasmin did not increase antibody production in ml/y mice, whereas the administration of various concentrations of copper suppressed the anti-SRBC plaque-forming response in both ml/y and +/y mice. 2) in vitro; ceruloplasmin had no effect upon antibody production against SRBC in both ml/y and +/y mouse spleen cells. In contrast to ceruloplasmin, 1 microgram/ml of copper inhibited the antibody production in spleen cells from both +/y and ml/y mice as well as in vivo. These findings suggested that the decreased antibody production in ml/y mice was considered to be due the decreased ceruloplasmin. PMID- 8488342 TI - Halothane anesthesia is neuroprotective in experimental spinal cord injury: early hemodynamic mechanisms of action. AB - The neuroprotective potential of halothane anesthesia was explored in a weight drop model of spinal trauma in the rat (N = 252). In initial experiments, animals were subjected to 25, 50 or 100 g cm impact injuries at T10 during pentobarbital or halothane anesthesia and their outcomes determined using somatosensory-evoked potentials, blinded neurologic evaluations for two weeks, and post-mortem analysis of spinal serotonin levels. Subsequently, halothane anesthesia was combined with either pentobarbital or nitrous oxide or given as a late treatment to pentobarbital anesthetized rats subjected to 50 g cm injuries. A series of acute studies were then performed in order to assess the hemodynamic and respiratory concomitants of halothane vs. pentobarbital, as well as the effect of mechanical ventilation and bicarbonate treatment upon halothane neuroprotection. Finally, the effect of a 50 g cm impact upon local white matter spinal cord blood flow was measured during halothane or pentobarbital anesthesia using laser Doppler flowmetry. Results demonstrate an active neuroprotective action for halothane anesthesia that is not altered by the presence of other anesthetics and is most prominent at severe injury levels. The data suggest the importance of immediate injury responses in this action. Late halothane treatment was ineffective when given as early as 10 minutes postinjury while both the electrophysiological and hemodynamic effects of halothane vs. pentobarbital were apparent during this 10 minute period. Thus, halothane was associated with the prevention of spinal ischemia during the first 10 minutes after trauma in comparison to pentobarbital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488343 TI - Influence of inorganic and organic arsenicals on intestinal transfer of nutrients. AB - The effects of organic (oxophenylarsine, PhAsO 2.5-50 mumol/l) and inorganic arsenicals (As2O3 2.5-250 mumol/l; As2O5 2.5-2500 mumol/l) on intestinal transfer of water, sodium, glucose and leucine was investigated in vitro using isolated jejunal segments of male Sprague Dawley rats. All three arsenicals decreased in a dose-dependent manner the transfer of water, sodium, glucose and leucine. At the highest concentrations investigated the amount absorbed was reduced to some 10 20% of the respective control values. For both glucose and leucine the concentration ratio between absorbate and perfusate was about 3.5-4 in controls. It decreased to about 2 for leucine and to near unity for glucose. As assessed from the concentration ratio between intestinal tissue and perfusate the arsenic compounds inhibited the uptake of glucose and leucine into the tissue. There was a marked difference with respect to the potency of arsenicals, PhAsO being about 10 times more potent than As2O3 which in turn was about 5 times more potent than As2O5. PMID- 8488344 TI - Influence of low luminal cadmium-concentrations on transfer of water and cadmium in the rat small intestine in vitro. AB - The sensitivity of the small intestinal water transfer for cadmium (Cd) exposure and its longitudinal gradient were investigated in luminally perfused intestinal segments in vitro and in vivo. Proximal segments accumulated Cd to a higher extent and, in addition, were more sensitive to Cd exposure than distal segments. In the proximal small intestine Cd impairs the intestinal water transfer at concentrations between 0.1 and 1.0 mumol/l in vitro and 4 mumol Cd/l in vivo. In vitro the Cd transfer from the intestinal tissue into the serosal absorbate declined in parallel to the reduction of the water transfer. In proximal but not in distal segments the declining water transfer corresponded to the decreases in glucose transfer in response to Cd exposure. According to literature the Cd effect on intestinal water transfer may be mediated by interaction of Cd with the Na-glucose co-carrier or by inhibition of the oxidative phosphorylation. The involvement of both mechanisms may differ along the small intestine. PMID- 8488345 TI - Coping amid uncertainty: an illness trajectory perspective. AB - This paper offers an alternative to the conventional social/psychological definition of "coping." Using a theoretical framework of "illness trajectory," the authors examine the uncertainty of temporality, body, and identity inherent in coping with cancer. Analysis then turns to the interaction among these uncertain conditions and the complex work processes described by people with cancer, as they tolerate, i.e., "cope with," the disease. Although presented separately for purposes of clarity, these processes and their related activities are experienced in varying combinations and with varying and fluctuating importance by each individual. Viewed comprehensively, however, they constitute the larger process of coping with cancer, with implications for other diseases as well. PMID- 8488346 TI - Praxis: a case study in the depoliticization of methods in nursing research. AB - This paper offers a case study in the depoliticization of the concept of praxis as it enters the nursing literature through Margaret Newman's (1990) paper Theory of Health as Praxis, which draws on Lather's (1986) description of 'research as praxis.' Newman's view of the relationship between consciousness and matter is contrasted with that of Marxism and her concept of health-illness is discussed. These considerations yield some examples of the liberal-democratic ideological position which underwrites her theory, and it is suggested that in drawing on the notion of praxis, Newman borrows from an ideology which is ultimately at odds with her theoretical construction of nursing. PMID- 8488347 TI - Toward a practice theory of caring for patients with chronic skin disease. AB - The purpose of this study was to provide a description and interpretation of the practical knowledge embedded in the practice of a group of experienced nurses caring for patients suffering from chronic skin disease. A practice theory was uncovered encompassing the nurses' underlying "model" of persons living with chronic skin disease, the values/goals for their care, action strategies utilized to realize the values, and the context framing their understanding and practice. The practice theory is proposed as a useful tool to systematize, communicate, reflect upon, refine, and extend the clinical practice of experienced nurses caring for this group of patients. The theory is also proposed as an example of how practical knowledge in other specialty areas may be systematized in order to communicate that knowledge efficiently. A scholarly discussion is needed about how best to communicate the invaluable resource of knowledge embedded in the practice of experienced nurses. PMID- 8488348 TI - The meaning of being homeless. AB - In this study, the meaning of the experience of being homeless as lived by 15 homeless women with dependent children is explored. The significance of being homeless is approached from what is known about the concept of home. Following a review of the literature, an identification of the sample, and an explanation of how data were collected, a three-level phenomenological method was utilized: description, reduction, and interpretation. The descriptive level generates seven themes: boundaries, connections, fatigue/despair, self-respect, self determination, privacy, and mobility. The reduction level reveals three ways of being homeless: physical, social, and symbolic. The interpretation of the meaning of being homeless employs the metaphor of homelessness as a whirlpool. Implications for nursing and social policy are discussed. PMID- 8488349 TI - [What is your diagnosis? Adenoid hyperplasia with narrowing of the nasopharynx]. PMID- 8488350 TI - [Diagnosis and therapy of colonic diseases]. PMID- 8488351 TI - [Irritable colon and constipation]. AB - Irritable bowel syndrome is a very common clinical problem with a broad spectrum of severity. The management includes a combination of positive diagnosis of typical symptoms with limited investigations to exclude underlying structural or biochemical disorders. Therapeutic trials focus on the relief of predominant symptoms. Identification and modification of factors exacerbating symptoms, behavioural techniques and pharmacologic agents directed to the presumed gastrointestinal motor dysfunction are required. Psychological support by the physician is the most important part of treatment. Chronic constipation may be the predominant symptom of irritable bowel syndrome. Underlying organic disorders must be excluded by clinical examination and endoscopy. Severe chronic constipation requires further investigation of colonic motility and defecation. High fibre diet, osmotic laxatives and procinetic agents may lead to an improvement. In rare cases surgery may be indicated. PMID- 8488352 TI - [Chronic diarrhea with special reference to ulcerative colitis and Crohn disease]. AB - There is a wide range of possible causes in chronic diarrhea. An attempt to correlate the symptoms with some clinically defined main categories facilitates a straight forward diagnostic approach. First and most important is a careful patient history. Very useful is a stratification regarding presence or absence of macroscopic lesions in the distal intestinal tract, usually done by coloscopy. Considering these principles, an overview of the most important causes for chronic diarrhea is given. Some relevant aspects of inflammatory bowel disease are discussed with special emphasis on the medical treatment. The major advantage of the newer 5-ASA compounds compared with sulfasalazine is the lower rate of side effects. 5-ASA enemas are very effective in the treatment of distal ulcerative colitis. Systemic treatment with corticosteroids is mandatory in severe case of ulcerative colitis and Crohn's disease. PMID- 8488353 TI - [Diverticulosis]. AB - Diverticula of the colon are very common in developed countries. In most of those affected diverticulosis is an asymptomatic condition. Only 20% complain of recurrent symptoms. Symptomatic diverticulosis is common only after the age of 50. Dietary treatment combined with antispasmodics is generally sufficient. Diverticular disease is complicated by bleeding or by diverticulitis in 20% of symptomatic patients. Diverticulitis itself can be complicated by intra-abdominal abscess, fistulas, perforation with generalized peritonitis or bowel obstruction. Each clinical appearance is described and treatment is discussed. PMID- 8488354 TI - [Acute diarrhea--current assessment and therapy in clinical practice]. AB - Acute diarrhea is most commonly caused by infectious agents. The first step in the evaluation is based on the medical history, clinical presentation and simple stool examinations (fecal leukocytes and occult blood). Thereby it can be decided, whether a microbial identification or an antibiotic therapy are indicated. In case of viral or noninvasive, enterotoxinogenic diarrhea oral rehydration is sufficient, whereas enteroinvasive diarrhea or enteric syndromes need further evaluation by stool and blood cultures. Depending on the clinical situation and the result of cultures, an appropriate or empiric therapy with antibiotics is indicated in acute febrile dysentery, shigellosis, cholera, typhoid fever, severe salmonellosis and Cl. difficile colitis. PMID- 8488355 TI - Resection for second and third primary lung cancer. AB - The continued increasing incidence of bronchogenic carcinoma increases the likelihood that a patient may develop a second or third primary tumor. We have carried out a second thoracotomy for 114 patients who met our criteria of having a new primary lung cancer. These criteria were a different histologic cell type, a tumor-free interval of 24 mo, the second primary in the contralateral lung, or the new tumor in a separate and distinct ipsilateral lobe if the tumor was on the same side. There were 18 patients who had a thoracotomy for a third primary lung cancer and they met the same criteria. There were 73 segmental resections in the 132 thoracotomies, and a conservative resection is important to minimize postoperative complications. Operative mortality for the second resection group of patients was 8.8% (10/114). There was one operative death in the 18 patients undergoing a third resection. The cumulative survival rate following a second resection in 114 patients with metachronous tumors was 33% at 5 yr and 20% at 10 yr. Early detection of a second and third primary lung cancer and surgical resection offers the greatest chance for long-term survival in this group of patients. PMID- 8488356 TI - Initial and reoperative pulmonary metastasectomy: indications, technique, and results. AB - The ability to predict which patients will derive a survival benefit from pulmonary metastasectomy is limited. Most patients remain asymptomatic until the disease becomes advanced, and therefore computerized tomography (CT) of the chest has become the standard of care for follow-up of patients at risk for pulmonary metastases. The most important predictor of post-thoracotomy survival in patients at the National Cancer Institute with soft tissue, osteogenic, and pediatric sarcomas as well as melanoma and renal cell carcinoma has been the ability to render the patient disease-free. Tumor histology, disease-free interval, and possibly number of nodules are also determinants of survival. Median sternotomy is the preferred approach for initial and repeat metastasectomies and every effort should be made to preserve pulmonary parenchyma. Resection of pulmonary metastases has become an accepted therapeutic modality, but selection of surgical candidates, and operative planning needs to be individualized. PMID- 8488357 TI - Primary tumors of the thoracic skeleton. AB - From 1975 to 1990, eighty-nine primary tumors of the thoracic skeleton; ribs, sternum, scapula, clavicle, and thoracic spine, were treated. Forty-four tumors (49%) were benign lesions. Forty-five tumors were malignant and were proportionately distributed amongst the five sites. The most common malignancies were Ewing's sarcomas, chondrosarcomas, plasmacytomas, osteogenic sarcomas, and lymphomas. All patients with Ewing's sarcomas were treated with combination chemotherapy, surgical resection, and radiation therapy for those with residual disease after surgery. Only one patient has died of disease. Patients with primary chondrosarcomas were treated by surgery alone and all are free of disease or have died without disease. Patients with solitary plasmacytomas or primary lymphomas of bone were treated with radiation therapy initially. Half the patients developed systemic disease. The patients with osteogenic sarcomas included several with radiation induced lesions and Paget's osteosarcoma and all but one died of disease. PMID- 8488358 TI - Superior results with complete resection of Askin's tumor. AB - A malignant small round cell tumor of the thoracopulmonary region arising in childhood has been described by Askin and colleagues. Subsequent descriptions have emphasized refinements (or disagreements) regarding pathology and emphasized the usual poor outcome. Complete excision has not been uniformly attempted in previous series. Our purpose is to describe superior results possible in a multidisciplinary setting emphasizing complete surgical excision. PMID- 8488359 TI - Recent developments in the epidemiology of lung cancer. AB - Lung cancer is currently the leading cause of cancer death in the United States and also the most common tumor worldwide. Changes in the distribution of histologic types over the past two decades in the United States, as well as high rates of lung cancer in certain subpopulations, require explanation. While cigarette smoking and specific occupational exposures are firmly established as important risk factors for lung cancer, recent work provides evidence that other factors may play a role either as independent risk factors or as modifiers of the effect of smoking. This paper reviews the epidemiology of lung cancer, with an emphasis on developments in the past decade. PMID- 8488360 TI - Comparative study of survival of screen-detected compared with symptom-detected lung cancer cases. Japanese Lung Cancer Screening Research Group. AB - Survival rates were studied in 1,297 screen-detected and 1297 symptom-detected patients with lung cancer. Resections took place in 20 hospitals and institutions in the Japanese Lung Cancer Screening Research Group. 60.6% of the screen detected lung cancer patients were from stage 0 to 11 and 39.4% were from stage III and IV. On the other hand, 27.1% of symptom-detected patients were from stage 0 to 11 and 72.9% were stage III to IV. In the screen-detected group, the tumor was peripheral in 83%, adenocarcinoma in 52.4% and the resectability rate was 66.5%. Five- and 10-year survival rates were 32.4% and 22.5% respectively in the screen-detected patients and 13.7% and 9.9% in symptom-detected patients. PMID- 8488361 TI - Diagnostic imaging and staging of primary lung cancer. AB - Improved diagnostic imaging has the potential to guide the surgeon in choice of invasive procedures required for staging and treatment of lung cancer. In the evaluation of a solitary pulmonary nodule, absence of growth for 2 years or certain typical calcifications are strong evidence of benignity, but we do not advocate following indeterminate nodules without a diagnosis because even small nodules may be carcinomas. In assessing chest wall invasion, computed tomography has no greater predictive value than a history of localized pain. The absence of nodes greater than 1.0 cm in short axis diameter on computed tomograms of the thorax is associated with low risk of tumor in mediastinal nodes, but tissue diagnosis is required for certainty. The finding of nodes larger than 1.0 cm may be useful in guiding the surgeon during staging procedures. Currently, there is no advantage of magnetic resonance imaging over computed tomography in evaluation of mediastinal nodes. Complete history and physical examination with routine serum chemistries will identify patients at high risk for metastases and will guide selection of appropriate special studies. It is emphasized that accurate staging requires histologic diagnosis and that CT and thorough surgical evaluation of the mediastinum are complementary procedures in staging of lung cancer. PMID- 8488362 TI - What controls should be used in studies of acute effects of alcohol and alcoholic beverages on the stomach and the pancreas? PMID- 8488363 TI - Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible? AB - Total gastrectomy or resection of the acid-producing part of the stomach (fundectomy) in the rat induced a marked and rapid reduction in bone wet weight, ash weight, and density (expressed as ash weight in mg/mm3 bone). Bone volumes were also affected but not as much. The radius, sternum, tibia, and femur were studied. Three weeks after gastrectomy the bone ash weight was reduced by almost 30% and the density by more than 25%. Maximum bone loss (approximately 40%) occurred about 6 weeks after the operation. The bone loss after gastrectomy was somewhat greater than that after fundectomy, whereas antrectomy had a marginal effect only. The percentage trabecular bone volume, calculated from morphometric analysis of histologic sections of the tibia, was greatly reduced by gastrectomy (approximately 50%), somewhat less so by fundectomy, whereas antrectomy had little effect. We set out to study whether calcium malabsorption could explain the bone loss after gastrectomy. Gastric acid is thought to facilitate the intestinal absorption of ingested calcium by mobilizing calcium from insoluble complexes in the diet. The possibility that lack of acid might contribute to the bone loss after gastrectomy was examined in experiments in which the proton pump inhibitor omeprazole was given for 4-8 weeks at such a dose (400 mumol/kg/day) that acid secretion was blocked almost completely during the period of study. This treatment was without effect on bone. However, the possibility could not be excluded that gastrectomized rats develop calcium deficiency for some reason other than lack of acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488364 TI - Non-Hodgkin's lymphoma and AIDS: frequency of gastrointestinal involvement in a large Italian series. AB - Even though the close association between AIDS and non-Hodgkin's lymphoma (NHL) is widely known, few studies have evaluated the frequency of gastrointestinal involvement in a large series of AIDS patients with heterogeneous risk factors. We therefore reviewed the demographic and clinical features of patients with AIDS and NHL seen at our institution over a period of 5 years. NHLs complicated AIDS in 70 of 786 (9%) cases in our study. All but one of the tumours were of high- or intermediate-grade histologic subtype, and 80% of 56 patients with diagnosis made during lifetime had disease stages III or IV, most with extranodal localization. The gastrointestinal tract was involved in 23 cases (33%), 13 of whom had an antemortem diagnosis. All these patients complained of significant symptoms, the most frequent being GI bleeding followed by recurrent abdominal pain with or without masses. Three patients had evidence of lymphomatous disease along both the upper and lower GI tract, but more often a single localization was present. Prognosis of patients with NHLs was very poor, and there was no significant difference in survival between patients with and without GI localization at the time of initial diagnosis. PMID- 8488365 TI - Effects of sedation and supplemental oxygen during upper alimentary tract endoscopy. AB - The effects of supplemental oxygen therapy on arterial oxygen saturation (SaO2) in unsedated and sedated patients have been studied using pulse oximetry. Hypoxia (minimum SaO2 92% or less) occurred in 41% of unsedated patients breathing room air but in only 11% (p < 0.01) of those receiving supplemental oxygen (41/min) by nasal cannulae. Comparable effects were seen in sedated patients (60% versus 16%, respectively, p < 0.01). Hypoxia during upper alimentary tract endoscopy is common with or without sedation and can be reduced by supplemental oxygen. PMID- 8488366 TI - Tumor necrosis factor-alpha potentiates phospholipase A2-stimulated release and metabolism of arachidonic acid in cultured intestinal epithelial cells (INT 407). AB - Tumor necrosis factor-alpha (TNF-alpha), a known pro-inflammatory cytokine, has been suggested to play a role in the pathogenesis of inflammatory bowel disease (IBD) by mediating damage to the intestinal epithelial cells. The present study demonstrates that TNF-alpha potentiates release and metabolism of 14C-labeled arachidonic acid (14C-AA) in cultured intestinal epithelial cells (INT 407). Although TNF-alpha on its own was but a weak stimulator of cellular 14C-AA turnover, it significantly potentiated the release of 14C-AA and 14C-labeled prostaglandin E2(14C-PGE2) after stimulation with three known phospholipase A2 activators: phospholipase. C from Clostridium perfringens, the calcium ionophore A23187, and the phorbol ester 4-beta-phorbol-12-myristate-13-acetate (PMA). The phospholipase A2 inhibitor quinacrine significantly reduced both AA and PGE2 release after combined stimulation with phospholipase C and TNF-alpha. In contrast to its effect on the AA turnover, TNF-alpha did not affect the phospholipase C-stimulated production of platelet-activating factor (PAF acether). Taken together, these findings indicate that a) TNF-alpha potentiates phospholipase A2-stimulated AA release from cultured intestinal epithelial cells; b) TNF-alpha may stimulate phospholipase A2-dependent AA release without affecting the formation of PAF-acether and c) pretreatment with TNF-alpha potentiates the formation of PGE2 after stimulation with phospholipase A2 activators. In summary, the present investigation points to the possibility that TNF-alpha may stimulate intestinal epithelial cells to produce biologically active AA metabolites and that this stimulation may be modulated by components of the intestinal luminal content, like bacterial toxins. PMID- 8488367 TI - Purification of lipase and other lipolytic enzymes from the human pancreas. AB - A pure lipase has been isolated from extracts of the human pancreas. The purification process includes centrifugation, two ion-exchange chromatography steps, and one gel filtration step. Compared with other reports, a high recovery, large amounts, and a high specific activity were obtained. Lipase is present at 1 2 mg/g in the pancreatic gland. In the absence of colipase and bile salts with tributyrine as substrate, the specific activity at room temperature and at pH 7.0 is 4000 mumol/min/mg. It increases to 8000-10,000 in the presence of colipase and bile salts at a temperature of 37 degrees C. The fate of the other human lipolytic proteins during the different purification steps is also indicated. Lipase purified by this method has been used for crystallization. PMID- 8488368 TI - The enkephalinase inhibitor, acetorphan, in acute diarrhoea. A double-blind, controlled clinical trial versus loperamide. AB - The antidiarrhoeal properties of acetorphan, an inhibitor of enkephalinase (EC 3.4.24.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs--that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan. PMID- 8488369 TI - A study of gastric emptying in non-ulcer dyspepsia using a new ultrasonographic method. AB - To ascertain the effect of gastric emptying on the symptoms of non-ulcer dyspepsia (NUD) patients, we randomly selected 60 NUD patients and, as control, 26 dyspepsia-free volunteers. We measured the gastric emptying time of mixed food (270 kcal), using real-time ultrasonography in two ways. NUD patients were divided randomly into two groups and given domperidone or placebo in a double blind trial. Of the NUD patients 48% had delayed gastric emptying times and associated epigastric pain, bloating, early satiety, and regurgitation. A prokinetic agent not only improved emptying time but also relieved some of the symptoms of the NUD patients. Real-time ultrasonography proved a useful method for evaluating gastric emptying. PMID- 8488370 TI - Adaptive protection related to clearance of ethanol in gastric mucosa of cats. AB - This study was designed to test the hypothesis that hyperemia after exposure to 2 M NaCl protects the gastric mucosa against damage caused by absolute ethanol by removing ethanol diffusing from the gastric lumen into the mucosa. The stomach of anesthetized cats was perfused with saline at pH 1.0. Gastric mucosal blood flow was determined by radioactive microspheres, and portal vein blood flow was measured by Doppler ultrasound flowmetry. The concentration of ethanol in the corpus mucosa and the amount of ethanol transported away from the stomach in portal blood were measured by using absolute ethanol containing trace amounts of 14C-labeled ethanol. Pretreatment with 2 M NaCl for 10 min increased mucosal blood flow and prevented the development of deep mucosal lesions after subsequent application of absolute ethanol. An inverse correlation was found between mucosal blood flow and the degree of ethanol-induced damage. The mucosal content of ethanol was low in animals pretreated with hyperosmolar NaCl, and the degree of mucosal damage was related to the tissue concentration of ethanol. The amount of ethanol transported by blood from the stomach increased with increasing mucosal blood flow. We conclude that the mild irritant, 2 M NaCl, increases mucosal blood flow, which protects the mucosa by removing ethanol diffusing from the lumen. Thus, the mucosal ethanol concentration remains below a level that causes damage. PMID- 8488371 TI - [Persistent vomiting]. AB - Vomiting is a physiological reflex to protect the body from harmful influences, whereas "pathological vomiting" occurs irrespective of its primary purpose or causes secondary disturbances. Artificially induced vomiting and enemas were prophylactic and therapeutic procedures to purge the body that were employed in ancient times and reached their zenith by the end of the 18th century. The act of vomiting is regulated by the vomiting centre, where neural afferents from the chemoreceptor trigger zone, vagal and sympathetic nerve system, and from other trigger areas, are coordinated. Differential diagnosis of vomiting, emphasizing metabolic/endocrine and psychogenic vomiting--including anorexia nervosa and bulimia--are briefly discussed. Symptomatic treatment of vomiting primarily consists of the use of receptor antagonists, e.g. dopamine, histamine and 5 hydroxytryptamine-3 antagonists. Acupuncture/-pressure are also discussed as an alternative treatment method. PMID- 8488372 TI - [Hematemesis. Extramural emergency]. AB - Hematemesis is the cardinal sign of upper gastrointestinal bleeding. It is a sign related to numerous affections, with a prognosis depending on the underlying lesion, the degree of bleeding, the accompanying disease and other risk factors. Mortality rates are generally close to 10%, although if hematemesis is secondary to variceal bleeding, as high as 30%. 65% of hemorrhages subside spontaneously, but 25% bleed recurrently (after initial cessation) and in 10% bleeding persists. Three quarters of all renewed bleeding occurs within two days after the initial hemorrhage. If hematemesis occurs outside a hospital, rapid evaluation is required to assess the necessity of emergency transport and treatment. In the case of severe to moderate bleeding, life-support measures and rapid transport to the nearest hospital are of primary importance and all measures complicating diagnosis and treatment in the hospital should be avoided. Patients with mild hematemesis, stable cardiovascular parameters and no risk factors can be investigated and, if appropriate, treated, on an out-patient basis. If the cause of hematemesis cannot be found, aggressive, inpatient investigations are required at the first sign of second bleed. Endoscopy is the primary investigative procedure for hematemesis. The success rate is highest if endoscopy is performed within the first 36 hours of the onset of bleeding. There are indications that aggressive diagnosis and therapy, including endoscopic hemostatic interventions, can reduce hematemesis mortality. PMID- 8488373 TI - [Internal bleeding in patients on oral anticoagulants]. AB - Five selected case reports of patients suffering from rather unusual bleeding complications during oral anticoagulant therapy are presented. The reported frequency of bleeding during oral anticoagulation varies greatly. An unacceptably high incidence of hemorrhages has been reported in North American studies of the early 1980ies. The therapeutic target INR of 2.5-4.9 in these series is comparable to that in European studies where bleeding occurred much less frequently. We suggest that the insensitive thromboplastin reagents used in North America are unsuited to guide coumarin dosage, because too many prothrombin time values were outside the INR target range. In contrast, most prothrombin time values in European studies where a sensitive thromboplastin reagent was used, were within the target range. A recent prospective investigation by 25 Swiss practitioners showed an acceptably low bleeding complication rate (2.1 hemorrhagic complications severe enough to necessitate hospitalization per 100 patient years). Observation of contraindications, regular control of the prothrombin time using a sensitive and correctly calibrated thromboplastin, participation of practitioners and hospital laboratories at quality control exercises and consideration of drug interferences with coumarins help to reduce the incidence of hemorrhagic side effects. In case of either a PT value outside the target range or manifest bleeding, the necessary measures have to be tailored to the individual situation considering the Quick value as well as the severity and localization of hemorrhage. PMID- 8488374 TI - [Emergency blood picture]. AB - Assessment of peripheral blood counts and blood film analysis are frequently performed as diagnostic procedures in emergency medicine. Far fewer situations exist, however, in which these analyses are the main clue in establishing an emergency diagnosis. Artifacts can lead to wrong diagnosis, e.g. pseudo thrombocytopenia, which is defined as a low platelet count resulting from a laboratory artifact. Severe neutropenia (agranulocytosis) and extreme hyperleukocytosis, as well as suspicion of acute leukemia, require a rapid diagnostic work-up. A newly detected anemia should not necessarily be treated by packed red cell transfusions. The decision whether an anemic patient ought to receive transfusions should be based on the speed with which the anemia has developed, as well as on clinical judgement. As a rule a chronic anemia patient with hemoglobin above 70 g/l does not need transfusions. An uncritical transfusion policy can even cause emergencies, e.g. in patients with megaloblastic anemia or in anemic multiple myeloma patients with a hyperviscosity syndrome. An elevated hematocrit requires prompt further investigations. This is of utmost importance if one considers the diagnosis of polycythemia vera rubra, a disease in which patients are particularly prone to thrombotic complications. Fragmented red cells (schistocytes) on peripheral blood smears constitute a cardinal diagnostic clue for the detection of microangiopathic hemolytic anemias (MAHA), in particular for the diagnosis of the life-threatening thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Malaria is another example for a chief role of blood smears examination in achieving a rapid diagnosis. If one encounters an unexpected severe thrombocytopenia, a marrow examination reveals whether it is due to rapid peripheral destruction, or due to a marrow failure. Furthermore, in any patients with an unanticipated thrombocytopenia, a disseminated intravascular coagulation and a MAHA should be ruled out. Heparin-induced thrombocytopenia is a rare, but possibly fatal complication of therapy with heparins. PMID- 8488375 TI - [Emergencies in patients with tumors]. AB - Oncological emergencies are frequent, particularly in advanced cancer stages. Many situations can only be tackled successfully with the cooperation of a well organized team of specialists. Spinal cord compression caused by cancer requires particularly swift action. The diagnosis should include a careful neurological examination. Myelography, once a classical approach in this setting, is increasingly being replaced by nuclear magnetic imaging techniques. Steroids should be given immediately after a diagnosis has been made and further treatment includes surgery, radiotherapy and/or chemotherapy, depending on the type of tumour involved. Febrile patients with severe neutropenia due to myelosuppression by cytostatic drugs often require treatment with intravenous antibiotics. Although hematopoietic growth factors are now available to hasten neutrophil recovery, these drugs should not be given on a routine basis. Another relatively frequent emergency is the superior vena cava syndrome, which is almost always due to a malignant tumour. Any treatment plan prepared to deal with an oncological emergency in a particular patient should take into account the prognosis of the underlying disease, the prospects for further therapy, and the patient's attitude. PMID- 8488376 TI - [Endocrine crises]. AB - Endocrine crises can occur in diabetes mellitus, in pituitary failure when there is a lack of ACTH, TSH or ADH secretion, in severe hyper- or hypothyroidism (thyroid storm and myxedema coma), severe hyper- or hypoparathyroidism (parathyroid crisis and tetany), in adrenal failure and in patients with pheochromocytoma or carcinoid tumors. Cushing's syndrome can be associated with psychotic crises. This review describes the most important clinical features and the basic diagnostic and therapeutic aspects of the non diabetic endocrine crises. PMID- 8488377 TI - [Hypercalcemia as an emergency]. AB - The hypercalcemic syndrome and the relation of serum calcium with the concentration of ionic calcium and albumin are shortly described. The pathogenetic significance of local, cytokine-induced bone destruction and of the osteoclast-stimulating effect by "parathyroid hormone related peptide" leading to "humoral hypercalcemia of malignancy" is underscored. In a hypercalcemic emergency the therapeutic strategy should combine adequate rehydration and induction of calciuresis by furosemide and the intravenous application of a rapid onset, calcium lowering substance such as calcitonin and, simultaneously, of a slow-onset, long-acting bisphosphonate such as pamidromate, which may be infused as a single dose. PMID- 8488378 TI - [3 dangerous electrolyte disturbances: hyponatremia, hyperkalemia and hypomagnesemia]. AB - Three cases of acute and potentially dangerous electrolyte disturbances provide a basis for discussion of selected aspects of pathogenesis, clinical manifestation and correction of certain electrolyte disorders (hyponatremia, hyperkalemia, hypomagnesemia). A case of diuretic-induced hyponatremia illustrates the controversy surrounding correction of this disorder. The regulatory mechanisms of transcellular potassium equilibrium are discussed with the help of a case of exercise-induced hyperkalemia. A separate case is dedicated to the discussion of the multiple causes and symptoms of magnesium depletion. PMID- 8488379 TI - [Urological emergencies]. AB - Every general practitioner has to deal with urologic emergencies. The most frequent illnesses are urinary retention, acute scrotum, priapism, macrohematuria, nephritic colic, obstructive pyelonephritis and pyonephrosis. Whereas urinary retention, as well as acute ureteric stone colic must generally be treated by the practitioner, the urologist must often be consulted in case of an acute scrotum or for priapism. Testicular torsion is one situation, where surgical treatment needs to be performed within 6 hours. Of utmost importance is his timely assistance with the obstructive pyelonephritis and pyonephrosis. These are initially often not recognized, especially because the first ultrasound examination of the intrarenal pyelone may not show a dilatation of the collecting system despite obstruction. If the adequate treatment with drainage and antibiotics is applied too late, this can result in serious and potentially lethal consequences. PMID- 8488380 TI - [Suffocation attack]. AB - An acute attack of suffocation is a life threatening event which may be fatal within minutes. Since the oxygen stores of the body are small, any interruption of oxygen uptake by the lungs results in immediate anoxia of tissue and in particular in perilous cerebral anoxia. The primary aims in the management of this emergency situation are: (1.) opening of the airways, clearing any obstruction, and keeping airways open; (2.) administration of oxygen and, if possible, assisted ventilation. This "reflex management" will gain time for diagnostic evaluation, for the decision about further management and, in most cases, for safe transport to the nearest emergency hospital. Further emergency measures are required in the case of upper airway obstruction due either to a foreign body or to laryngeal edema caused by local insect stings or anaphylaxis. Occasionally a foreign body obstructing the upper airways can be cleared using the Heimlich maneuver, i.e. rapid inward and upward pressure on the victim's epigastrium. Mild forms of laryngeal edema can be relieved by inhalation of epinephrine. If these methods fail, cricothyroidotomy or transtracheal ventilation must be performed. Patients with acute severe asthma must be immediately treated with inhalations of a beta-agonist, parenteral prednisolone and administration of oxygen, while emergency transport to the nearest hospital must be organized. To ensure first aid the emergency physician must be equipped with the necessary instruments such as a small oxygen cylinder, appropriate cannula with connectors and tubings for transtracheal ventilation, and a suitable bag-valve-mask device. PMID- 8488381 TI - [Stroke]. AB - Stroke is an ischemic event in 80% and hemorrhagic in 20%, which can be distinguished by computed tomography of the brain. Unfortunately, no routinely applicable therapy is available for stroke. Several thrombolysis studies are underway and their results will become available in the next few years. Hemodilution has been abandoned except for hematocrits above 50%. Calcium antagonists such as nimodipine reduce vascular spasms after subarachnoidal hemorrhage, but their administration after ischemic stroke is unsuccessful. A new experimental approach is offered by glutamate receptor antagonists, which may prevent cell damage induced by the excitatory amino acid glutamate. In the case of cardio-embolic stroke, heparin should be started after 48 hours. Hypertension should only be treated above values of 200/120 mm Hg, with short-acting intravenous drugs. Because of the limited therapeutic options for completed stroke, primary prevention (treatment of hypertension, anticoagulation for atrial fibrillation) and secondary prevention after transitory ischemic attacks (endarterectomy for carotid stenosis > 70%, aspirin) should be intensified. PMID- 8488382 TI - [Acute loss of vision due to ocular perfusion disorders]. AB - Particularly in patients over 40 years of age, disturbances of perfusion at the optic nerve head and retina are a frequent cause of acute visual acuity loss. As the most important disease entities, we must distinguish between ischemic optic neuropathy and arterial and venous perfusion disturbances. The prognosis with regard to visual acuity is, at any rate, serious: a considerable, persistent loss of vision must be expected. Unfortunately, at present there is no therapy available which could normalize perfusion quickly enough. In individual cases of ocular venous thrombosis, isovolumetric hemodilution can be effective. Use of argon-laser coagulation may markedly reduce the occurrence of severe complications (hemorrhagic glaucoma, vitreous bleeding). As an emergency measure, brief massage of the globe as well as administration of 100 mg prednisone and 250 mg acetazolamide are recommended. Disturbances in ocular perfusion call investigation with regard to hematological and vascular risk factors. It is always important to rule out giant-cell arteritis (Horton's disease). PMID- 8488383 TI - [Acute headache]. AB - Sudden, explosive headache is rather rare. Though dramatic for the patient and the physician, it does not necessarily herald an intracranial catastrophe. Benign and dangerous thunderclap headaches cannot be distinguished from the features of headache itself, but rather on the basis of the situation, the additional symptoms and the findings. This means that every sudden headache should be considered potentially dangerous and be investigated immediately. The dangerous forms comprise intermittent hydrocephalus, acute bacterial meningitis and above all vascular complications. Subarachnoid hemorrhage frequently must be ruled out by computed tomography and lumbar puncture. Intracerebral, especially cerebellar hemorrhage, as well as hypertensive crisis require immediate treatment. Fatal cerebral embolism complicating spontaneous dissection of craniocervical arteries (carotid or vertebral arteries) can be prevented by early anticoagulant therapy. To confirm diagnosis, additional investigations such as CT, lumbar puncture or cerebrovascular ultrasound, and in rare cases MRI, should be performed early as the available time for effective therapy in many situations is short. Many of the benign forms of sudden headache can be diagnosed with a focused interview (cold or drug induced and food dependent headaches, sinusitis, glaucoma). Others, such as neuralgia, cough and coital headache, can be diagnosed as benign only when additional investigations have ruled out symptomatic forms. PMID- 8488384 TI - [Emergency: the internist as psychiatrist]. AB - Aspects of psychiatric emergencies of special interest to the general physician are discussed. The perception that a problem constitutes an emergency is often subjective and sometimes reflects the anxieties of others rather than a real need for urgent treatment. Keeping calm and unhurried in front of an agitated patient might be as important as the use of a neuroleptic. The rather unusual psychopathological phenomena catalepsy and psychogenic twilight state (psychogenic trance) are mentioned in view of their importance for urgent assessment of mental status. The scope of the problem of suicide is outlined as far as the general physician is involved. Special attention is paid to panic disorder and attacks, a relatively new concept in medicine. Since the symptoms mimic those of cardiac, endocrine and convulsive disorders, patients with such symptoms often come to the attention of general physicians and frequently use the services of emergency departments. Early identification and treatment of panic disorder might help to avoid unnecessary repeated emergency department visits, and at the same time reduce the associated high risk of suicide and other psychiatric disorders such as depression as well as drug and alcohol abuse. PMID- 8488385 TI - ["Needlestick" accidents--procedures following potentially infectious exposure in medical personnel]. AB - Accidental exposure to blood carries with it a definite risk for the health care worker of infection by various bloodborne pathogens, especially the hepatitis B, hepatitis C, and human immunodeficiency virus. The risk of transmission from exposure to HIV is lower than that associated with exposure to HBV and HCV. Should HIV infection occur, however, the outcome is likely to be fatal. Although general infection control precautions, safer use of needles, gloves, and other procedures may substantially reduce the incidence of occupational exposures, they cannot eliminate the risk completely. The post-exposure management is discussed. Neither the efficacy nor the safety of AZT (zidovudine) for use as a chemoprophylactic agent following occupational exposures to HIV has been established. Nevertheless in selected cases it can be proposed to health care workers. PMID- 8488386 TI - [Fever with chills]. AB - Abrupt onset of fever with chills represents a body response to various stimuli called exogenous pyrogens. These substances interact with monocytes and macrophages, thus releasing various cytokines including interleukin-1 and tumor necrosis factor (endogenous pyrogens). Endogenous pyrogens act centrally on the thermosensitive neurons in the hypothalamus to increase the core body temperature by increasing heat production and decreasing heat loss. In addition, endogenous pyrogens trigger a non-specific inflammatory response and amplify the specific immune response through activating the T- and B-cell system. Pyogenic infections are the most frequent and most important cause of abrupt onset of fever with chill, but a similar pattern of fever may occur in many other situations. In many instances, a thorough history and a complete physical examination will produce a presumptive diagnosis. Further management decisions depend on the clinical conditions and on the localization of the infection. Patients with compromised vital functions, with involvement of the central nervous system, with chills associated with prolonged fever without localizing symptoms or physical findings, or with symptoms of intraabdominal sepsis, must be promptly hospitalized. The most important aspects of treatment should be directed at the cause of fever, and antipyretic drugs should be used after evaluation of relative risks in the individual case. PMID- 8488387 TI - [Give credit where credit is due?]. PMID- 8488388 TI - [Meetings of the Swiss Societies of Internal Medicine, Rheumatology, and Rehabilitation and Physical Medicine. Lausanne, 13-15 May 1993. Abstracts]. PMID- 8488389 TI - [The immunohistochemical picture in transfusion of incompatible blood]. AB - To provide evidence of transfusion of incompatible blood in the ABO system in forensic medicine also antigens A and B of the donor must be detected in the body of the recipient. The author presents his own experience with evidence of incompatible red blood cells with group properties A, B or AB by the indirect immunoperoxidase method in paraffin section of the recipient's tissues. A positive reaction makes it possible to detect also occasional incompatible erythrocytes in particular in the periphery. An advantage is in particular the high sensitivity of the method, and as paraffin tissue blocks are used, also the possibility of retrospective evaluation. PMID- 8488390 TI - [Complications of thermal injuries leading to death]. AB - The authors analyzed a group of 194 decreased subjects, 119 men and 75 women aged 15.96 years who suffered thermic damage in the years 1981-1989. As compared with the source of burns in 1966-1974, there was a striking increase of subjects who suffered burns during propane-butane explosions. In the foreground of thanatological findings was pneumonia in 49%, shock in 28.3%, sepsis in 26.8% damage of the upper gastrointestinal tract in 23.7% and thrombotic embolism in 18% of the subjects who died. More than half of them died with normothermia, 25% with hyperpyrexia and more than 20% with hypothermia. As compared with values of LA50 in 1966-1974 an increase occurred which implies a more favourable prognosis of burns. The values of LA50 were higher in particular in in the age group from 15-50 years. PMID- 8488391 TI - [Forensic evaluation of drowning]. AB - The authors discuss the basic types of the mechanism of drowning and different findings on necropsy. They draw attention to some endogenous and exogenous factors which participate in the development and course of drowning and changes which occur when the corpse is in water for prolonged periods. On examples from practice they demonstrate difficulties which may influence the diagnosis, in particular uncommon interferences with the organism. PMID- 8488392 TI - Chemotherapy-induced alopecia: new developments. AB - Alopecia (hair loss) is one of the most physically and psychologically distressing side effects of cancer chemotherapeutic drugs. Since its first recognition as a common outcome to most chemotherapeutic agents, only a few trials have been reported, using either a method to temporarily reduce the scalp blood flow (scalp tourniquet or hypothermia) or vitamin E, with undocumented and variable efficacy. The lack of progress in the treatment and prevention of chemotherapy-induced alopecia is in part due to the lack of a reproducible animal model. In the past 2 years, we reported on the following observations: (1) treatment of 8-day-old rats with vidarabine (ara-C), doxorubicin, and cyclophosphamide consistently produced either total body alopecia (ara-C and cyclophosphamide) or alopecia confined to the head and proximal part of the back (doxorubicin); (2) Imuvert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against alopecia induced by ara-C and doxorubicin but not that produced by cyclophosphamide; (3) the protective effect of Imuvert against chemotherapy induced alopecia is mediated by a monocyte-mediated cytokine; and (4) this monocyte-derived cytokine is, possibly, interleukin-1. These observations constitute important progress in the understanding and prevention of chemotherapy induced alopecia. PMID- 8488393 TI - Ondansetron: a novel antiemetic agent. AB - Ondansetron hydrochloride is a new serotonin receptor antagonist that is effective in preventing emesis associated with cancer chemotherapy. The antiemetic effect appears to be exerted through a peripheral vagal blocking within the gastrointestinal tract, as well as an inhibitory effect within the chemoreceptor trigger zone (CTZ). Plasma concentrations of ondansetron peak 1 hour after an oral dose, and the tablet has an absolute bioavailability of 59%. Ondansetron undergoes extensive hepatic oxidative metabolism in the liver. The half-life of ondansetron is 3.5 hours in healthy volunteers; elderly patients have a slightly reduced clearance, and pediatric patients have increased clearance. Although less than 10% of ondansetron is recovered unchanged in the urine, most metabolites are eliminated by this route. The recommended dose of ondansetron is 0.15 mg/kg for three doses on the day of chemotherapy (30 minutes before chemotherapy and 4 and 8 hours afterward). An alternative regimen includes a single-day dose of 32 mg IV in adult patients before chemotherapy. The efficacy of ondansetron therapy for delayed emesis has not been determined. Ondansetron has proven to be appropriate as a single agent or as an addition to standard antiemetic therapy (ie, corticosteroids, benzodiazepines, neurotransmitter blockers) in preventing and treating acute chemotherapy-induced emesis (CIE). Initial results of clinical trials in prevention of radiotherapy-induced emesis and anesthesia-induced emesis appear positive. Ondansetron is well tolerated, with few adverse events (eg, headache, sedation). PMID- 8488394 TI - Open trial of fluoxetine therapy for premenstrual syndrome. AB - To assess the possible efficacy of fluoxetine hydrochloride in severe PMS (premenstrual syndrome, luteal phase dysphoric disorder), an open trial of this medication was undertaken on women with severe PMS. Of 38 patients seeking evaluation of PMS, 35 met the criteria for diagnosis, and 21 had mild symptoms and were treated symptomatically. Fourteen had more severe symptoms persisting for more than 5 to 6 days of the month, and 11 elected to participate in an open trial of low-dose (20 mg) fluoxetine, an antidepressant. Ten continued treatment for 3 to 20 months, with moderate to marked relief of symptoms during treatment and without problematic side effects (one patient was given 40 mg daily; the remainder received 20 mg daily). On discontinuing therapy, seven have had persisting remissions, and two have returned for another cycle of fluoxetine therapy, with relief. It is unclear whether such a strong positive response to fluoxetine, an antidepressant with particularly good effects in "atypical depression," indicates that the women affected by severe PMS have a cyclic, hormonally induced change in brain chemistry causing a depressive type of condition, or whether they have a true (atypical) mild depression with brief remission due to "perifollicular euphoria" in the estrogenic follicular phase. PMID- 8488395 TI - Emphasis on high-density lipoprotein cholesterol in patients with coronary artery disease. AB - Although numerous epidemiologic and lipid intervention studies clearly demonstrate the pivotal role of high-density lipoprotein cholesterol (HDL-C) on risk of coronary artery disease (CAD), the National Cholesterol Education Program (NCEP) has emphasized only total cholesterol and low-density lipoprotein cholesterol (LDL-C), and has underemphasized the role of HDL-C in their lipid assessment and treatment recommendations. In a review of 113 consecutive patients in our cardiac rehabilitation program, lipid levels improved modestly with cardiac rehabilitation. "Ideal" lipids (LDL-C < 130 mg/dL according to the NCEP) were present in 49% before the rehabilitation program and in 46% afterward. In fact, 60 (53%) of our patients had total cholesterol levels < 200 mg/dL and would require no further lipid assessment or treatment according to the NCEP. Of these 60 patients, 40 (67%) had low HDL-C (< or = 35 mg/dL). In our total study group, 56% (63/113) had HDL-C < or = 35 mg/dL and 33% (37/113) had HDL-C < or = 30 mg/dL before rehabilitation (compared to 42% and 21%, respectively, after rehabilitation. On the other hand, a "high-risk" LDL-C value (> or = 160 mg/dL) was found in only 17% of patients at baseline and in only 13% after the cardiac rehabilitation program. Using an approach that incorporates the pivotal role of both LDL-C and HDL-C (LDL-C > or = 160 mg/dL or HDL-C < or = 35 mg/dL) for our patients with known CAD, 65% would require drug treatment before rehabilitation and 53% after rehabilitation. We conclude that: (1) lipids improve only modestly (though the change is significant statistically) with cardiac rehabilitation; (2) low levels of HDL-C are prevalent in cardiac rehabilitation patients and are much more prevalent than elevated LDL-C, both before and after rehabilitation; and (3) the NCEP should reevaluate the pivotal role of HDL-C in its assessment and treatment guidelines, particularly in patients with known CAD, since emphasis on both LDL-C and HDL-C is needed for optimal primary and secondary prevention of CAD. PMID- 8488396 TI - Conservative surgery and radiation therapy in early breast cancer: ten-year experience at the West Florida Cancer Institute. AB - Between July 1981 and December 1989, 143 patients received conservative surgery and radiation for 147 primary breast tumors. Ten lesions were staged as Tis, 122 as T1, and 15 as T2. N stages were NX in 15 cases, N0 in 93, and N1 in 39. All patients had lumpectomy, and 132 (89%) had axillary lymph node dissection. All had irradiation (45 to 50 Gy) to the entire breast. All received an electron boost to the primary site to a total dose of 60 Gy. Minimal follow-up was 18 months, and median follow-up was 56 months; 123 patients had at least 3 years of follow-up, and 59 patients had at least 5 years. The local control rates at 3 and 5 years were 96% and 97%, respectively. Tumor-free states at 3 and 5 years were 93% and 86%, respectively. Minor complications occurred in four patients. Approximately 90% of patients had good to excellent cosmetic results. PMID- 8488397 TI - Treatment of acute intestinal ischemia with hyperbaric oxygen. AB - Hyperbaric oxygen has been shown to improve oxygen tension and promote wound healing. We did a pilot study in which we created ischemic jejunal segments measuring 3, 6, and 9 cm, 10 of each length, in 30 rats. Half of the rats were given hyperbaric oxygen at 100%, 30 psi, for 90 minutes twice daily for 7 days to determine whether hyperbaric oxygen therapy could overcome the ischemic intestinal injury and prevent ischemic necrosis. In the rats with 6- and 9-cm ischemic segments, no difference was seen between the hyperbaric oxygen and control groups. Of the rats with 3-cm ischemic segments, ischemic infarction of the bowel developed in 40% of the hyperbaric oxygen group and 100% of the controls (P = 0.167, Fisher's Exact Test). We then created 3-cm ischemic intestinal segments in 30 additional rats. Again, half were treated with hyperbaric oxygen as previously described for 7 days. There was no difference between the controls and the hyperbaric oxygen group in the rate of perforation (4 of 15 [27%] versus 1 of 15 [7%]) or stricture rate (8 of 15 [53%] versus 9 of 15 [60%]). We concluded that hyperbaric oxygen therapy is of limited value for the treatment of intestinal ischemias. PMID- 8488399 TI - Factors predicting reluctance to seek treatment in patients with eating disorders. AB - Eating disorders, including anorexia nervosa and bulimia nervosa, are common problems in young women, yet many delay or never seek treatment for them. A semistructured telephone interview that addressed various eating problems was conducted with 78 consecutive patients referred to a university hospital eating disorders clinic. It was hypothesized that individuals who subsequently followed through with treatment would differ in some easily recognizable characteristics from those who did not. No significant differences were found in variables, including duration of eating problems, frequency of binge eating or vomiting, history of previous treatment, or presence of associated physical problems. However, individuals who abused laxatives, those with depression, and those who were least satisfied with their current weight tended to avoid coming to the clinic for treatment. These findings suggest that individuals with more severe eating problems may be the most reluctant to seek treatment. PMID- 8488398 TI - STAR complexes: febrile illnesses associated with sore throat, arthritis, and rash. AB - Between January 1990 and February 1991 we evaluated the cases of 20 patients for a symptom complex consisting of Sore throat, elevated Temperature, migratory Arthritis, and a pruritic urticarial Rash (STAR). The patients ranged in age from 3 1/2 to 48 years; most were from central Texas. Duration of illness varied from 2 weeks to longer than 1 year. Results of laboratory studies included the following abnormal findings: elevated erythrocyte sedimentation rate, leukocytosis, anemia, and thrombocytosis. Eleven of 18 (61%) patients had low antinuclear antibody titers. HLA-A2 was noted in 8 of 10 (80%) of those tested. Test results were positive in eight cases for IgM antibodies to parvovirus and in six cases for IgM antibodies to rubella, suggesting that these entities may represent an underdiagnosed cause of STAR complex. In six cases no specific cause of disease was found; these cases may be attributable to other infectious agent(s) yet to be identified. Here we present a description of the cases, a discussion of the differential diagnosis, and an evaluation of STAR complex. PMID- 8488400 TI - Cerebral monitoring during implantation of automatic internal cardiac defibrillators. AB - Implantation of automatic internal cardiac defibrillators (AICD) for management of arrhythmias necessitates the induction of ventricular fibrillation (VF) to test the device adequately. The profound hypotension associated with induced arrhythmia and subsequent circulatory arrest may result in cerebral ischemia. To characterize cerebral ischemia, we used a five-lead Lifescan brain activity monitor to examine changes in cerebral activity in 10 patients having AICD placement. The duration of hypotension, as defined by a mean arterial pressure (MAP) < 50 mm Hg, was recorded, and the corresponding changes in brain activity were evaluated during 51 episodes of circulatory arrest. The number of episodes for each patient ranged from 2 to 14. The average duration of hypotension per episode was 26.2 seconds, with a range of 8 to 67 seconds. Brain activity changes characteristic of cerebral ischemia occurred in 46 of the 51 events (90%). Cerebral ischemia did not occur when the duration of hypotension was less than 16 seconds (5 episodes). The duration of cerebral ischemia ranged from 50 to 279 seconds (average 84.9 seconds) and did not correlate with the duration of hypotension or the order of the episodes in the testing sequence. These findings suggest that reevaluation of standard monitoring practice for AICD implantation may be warranted. PMID- 8488401 TI - Human immunodeficiency virus infection: knowledge of the disease and attitudes toward related issues and policies among health care workers in a low-incidence nonurban hospital. AB - We compared the knowledge and attitudes regarding human immunodeficiency virus (HIV) infection among employees in a tertiary care teaching hospital in a nonurban southeastern city with a relatively low incidence of acquired immunodeficiency syndrome (AIDS). All 260 physicians and a random sample of 240 other employees were asked to complete a 59-item anonymous mail survey. All groups of respondents, including physicians, showed a lack of understanding of critical aspects of AIDS, particularly transmission. Negative attitudes such as victim blaming and not liking to care for persons with HIV infection were common, especially among house staff and respondents who do not give hands-on care. Misinformation, aversion, fear, and lack of compassion were evidenced by a substantial proportion of the respondents, particularly house staff. The attitudes expressed suggest that there is more focus on the rights of the caregiver than on the welfare of patients. These findings show that there is a need for medical education that focuses on both knowledge and affective issues of HIV infection. PMID- 8488402 TI - Effect of hemodialysis on left ventricular contractility in pediatric patients with end-stage renal disease. AB - Assessment of the effect of hemodialysis on myocardial contractility is complicated by variations in loading conditions that can occur during hemodialysis and by the prevalence of coronary artery disease among patients with chronic renal failure. Therefore, we used a load-independent index of left ventricular contractility, derived from analyses of the rate corrected velocity of circumferential fiber shortening (Vcfc)-end systolic wall stress (ESWS) relationship, to study the acute effects of hemodialysis on left ventricular function in the cases of 15 pediatric patients with end-stage renal disease. Prior to dialysis, Vcfc was appropriate for ESWS (102% +/- 16% of predicted) and did not differ significantly from values obtained from a group of nine normal control subjects of similar ages (103% +/- 9% of predicted), indicating that the patients' left ventricles were functioning in a normal inotropic state. After dialysis, Vcfc increased to levels beyond those expected for ESWS (118% +/- 20% of predicted, P < .05 versus control; P < .001 versus predialysis levels), indicating that dialysis was associated with enhancement of the left ventricle's inotropic state. A statistically significant increase in plasma norepinephrine levels was also observed. However, the increase in the percentage of the predicted Vcfc did not correlate with observed changes in this inotropic agent or with dialysis-induced variations in body weight or levels of electrolytes, urea nitrogen, or creatinine, and firm conclusions regarding the identity of the factors responsible for the positive inotropic effect of hemodialysis could not be drawn. PMID- 8488403 TI - More short-term volunteer staffing for public health: an independent policy statement. AB - This paper is an independent policy statement recommending more short-term volunteer staffing for the US Public Health Service. I propose a Public Health survey of all physicians to determine their willingness to serve short-term, so that those available can be mobilized. Public Health should redirect its recruitment efforts, eliminate bureaucratic hindrances, develop a cadre of generalists and specialists, and designate appropriate organizations that can incorporate existing medical personnel. PMID- 8488404 TI - Trauma surgery during the Civil War. PMID- 8488405 TI - Spontaneous migration of an intracranial bullet into the cervical canal. AB - We have reported a case of intracranial to intraspinal migration of a retained bullet fragment over a course of approximately 4 years. The patient remained asymptomatic. The bullet was removed via a posterior cervical laminectomy. Migration of bullet fragments, though rare, should be included as one of the delayed complications of gunshot wound to the head. PMID- 8488406 TI - Respiratory insufficiency in adult-type acid maltase deficiency. AB - AMD is a glycogen storage disease that affects all age groups. In both childhood and adult forms, the classic clinical picture is that of a progressive myopathy that may resemble polymyositis or limb girdle muscular dystrophy. Respiratory muscle involvement is common, may occur early in the course of the disease, and is the most frequent cause of mortality from AMD. These findings underscore the need to consider AMD in the differential diagnosis of unexplained respiratory insufficiency. We have described the case of one patient in whom respiratory failure was the initial symptom and two other cases in which the patient had progressive muscular weakness and subsequent respiratory failure. A review of the literature revealed that respiratory muscle weakness has been reported in 21 of 43 cases of AMD in adults. In 10 cases respiratory insufficiency was preceded by only mild or moderate weakness. PMID- 8488407 TI - Multiple myeloma and AL amyloidosis mimicking Sjogren's syndrome. AB - A 49-year-old white man had xerostomia, orthostatic hypotension, salivary gland enlargement, and a monoclonal gammopathy. Salivary gland biopsy revealed AL amyloidosis without histopathologic evidence of Sjogren's syndrome; serologic evidence of Sjogren's syndrome was also absent. Bone marrow biopsy revealed more than 30% plasma cells, and a diagnosis of multiple myeloma was made. The association of myeloma amyloidosis with salivary gland infiltration and xerostomia is rare. Unusual causes of xerostomia, such as myeloma amyloidosis, should be considered when histopathologic and serologic evidence of Sjogren's syndrome are absent. PMID- 8488408 TI - Silicone pleural effusion due to iatrogenic breast implant rupture. PMID- 8488409 TI - External iliac artery occlusion due to pelvic fracture: management with a cross femoral bypass graft. AB - Vascular injury is not uncommon in cases of major pelvic trauma. Venous injury is by far the most common associated problem and may lead to exsanguinating hemorrhage. Arterial injury is less common, but certainly not without associated morbidity and mortality. It can lead to persistent bleeding after fixation and stabilization of the pelvic girdle, and occlusion of major pelvic arteries can cause limb ischemia and limb loss. The potential problems with revascularizing the ischemic extremity are (1) other life-threatening injuries that may be present and (2) a retroperitoneal hematoma that can interfere with an anatomic approach. Our solution to the latter problem, as presented here, is placement of a cross-femoral bypass graft, which rapidly and safely restores blood flow in the presence of pelvic fracture and an occluded external iliac artery. The pelvic hematoma is avoided, thereby restoring circulation more quickly, with less blood loss and greater ease. PMID- 8488410 TI - Acute Page kidney phenomenon: a cause of reversible renal allograft failure. AB - We have reported a case of reversible acute renal transplant failure due to the Page kidney phenomenon, which followed routine diagnostic needle biopsy. Duplex Doppler ultrasonography differentiated between allograft rejection and graft failure due to perirenal and mechanical abnormalities. Renal transplant failure may result from intrinsic or extrinsic allograft compression. If this is detected and treated rapidly, renal deterioration may be reversed and the transplant salvaged. PMID- 8488411 TI - Pylephlebitis associated with diverticulitis. AB - We have reported the cases of two patients who had acute pylephlebitis associated with portal vein thrombosis and septic hepatic emboli as a result of right colonic diverticulitis. Although rare, pylephlebitis is a treatable but often lethal complication of intra-abdominal sepsis. Several bacterial pathogens, especially Escherichia coli are associated with pylephlebitis. Early suspicion and prompt antibiotic therapy can lead to resolution of portal vein thrombosis and hepatic abscess formation, resulting in full recovery for the patient. Surgery may not be required. Our two patients received ampicillin--the best first line drug--until specific antibiotic therapy could be given. Early administration of a broad spectrum antibiotic is essential. PMID- 8488412 TI - Pyoderma gangrenosum as a cutaneous manifestation of diverticular disease. AB - We have described a case of pyoderma gangrenosum due to diverticular disease. The patient was an elderly woman with a 3-month history of cutaneous disease without associated gastrointestinal complaints. There was no history of inflammatory bowel disease, malignancy, or seropositive arthritis. Evaluation revealed a retroperitoneal abscess due to a ruptured diverticulum. Surgical resection of the affected colon led to rapid and complete resolution of all symptoms. Pathologic examination of resected tissue showed diverticulitis without evidence of chronic inflammatory bowel disease. PMID- 8488413 TI - Symptomatic pleural effusion after coronary artery revascularization: unsuspected pleural injury from internal mammary artery resection. AB - A patient with a large left pleural effusion returned to her physician 4 weeks after CABG with saphenous vein grafts. After repeated investigations the cause of the effusion still could not be ascertained. Upon subsequent review it was noted that the patient had had an aborted attempt at coronary artery revascularization using the left IMA. Nonsurgeons frequently fail to recognize the association of significant pleuropulmonary complications with harvesting of the IMA conduit as a coronary bypass graft. The delay in presentation of these complications after CABG, along with a lack of physician familiarity with them, can lead to problems in diagnosis and management. Although serious pleuropulmonary complications are an uncommon problem, physicians must become familiar with these complications because of the widespread use of the IMA graft. PMID- 8488414 TI - Peritonitis due to Moraxella (Branhamella) catarrhalis in a diabetic patient receiving peritoneal dialysis. PMID- 8488416 TI - Minimalism in surgery. PMID- 8488415 TI - Tetanus, pseudotetanus, or conversion disorder: a diagnostic dilemma? AB - Failure to consider conversion disorder in a patient with acute, tetanus-like symptoms led to unnecessary medical expenditures and delayed appropriate psychiatric intervention. Patients presenting these clinical symptoms need a comprehensive evaluation, with careful attention to details in the psychosocial history. While tetanus is rarely encountered now in the United States, conversion disorder is commonly encountered in both medical and psychiatric populations. PMID- 8488417 TI - "Mister Christopher Columbus". PMID- 8488418 TI - "Mister Christopher Columbus". PMID- 8488419 TI - Use of ketorolac (Toradol) to inhibit perioperative platelet aggregation. PMID- 8488420 TI - [The significance of the ultrasound examination in surgery of the thyroid gland]. AB - The authors emphasize the importance of ultrasonographic examination of the thyroid gland for the diagnosis of disease as well as for planning and implementation of the operation. They evaluate the importance of 154 sonographic examinations which were made during the last three years in 545 operations of the thyroid. For the surgeon anatomical parameters of the pathological tissue are important with special emphasis on the relation with surrounding tissues and affection of the lymphatic system. The examination is irreplaceable, in particular in reoperations of the thyroid gland and nodular syndrome. PMID- 8488421 TI - [The importance of annulo-ventricular integrity in replacement of the mitral valve. Experience with the double-disc low profile Carbo Medics mechanical valve]. AB - In the submitted paper the authors compare the results of the conventional replacement of the mitral valve with total excision of the subvalvular apparatus and the results of mitral replacement with a completely or partly preserved or reconstructed integrity of the annulopapillary structures. During the last five years the authors operated by the former method 115 patients (group A) and the second surgical method was used in 93 patients (group B). In both groups the authors compared 33 demographic, clinical, peroperative, postoperative and echocardiographic indicators. Group B comprised substantial more patients with severe myocardial disorders. In the latter group significantly more frequently a mechanical double-disc valve Carbo Medics was implanted than other types of synthetic valves which were used mostly in patients of group A. In patients of group B the operation took longer and after operation they needed more frequently intense inotropic support. Despite that their mortality on hospitalization was lower -3.2% than in group A where it was 6.9%. The late echocardiographic results were also in favour of group B where, contrary to group A, after operation the left ventricular function improved. The authors' experience support the view that preserving the integrity of the annulopapillary apparatus is nowadays one of the demands in surgical correlation of a mitral defect and is of decisive importance for the subsequent fate of the thus treated patients. PMID- 8488422 TI - [Use of the right gastroepiploic artery graft in revascularization of the myocardium]. AB - The right gastroepiploic artery (rGEA) was used as a graft for revascularization of the heart muscle in 239 patients along with other arterial grafts obtained from the internal mammary arteries (IMA). The mean follow-up of patients after operation was 17 months, the longest period being 38 months with a total follow up period of 4,063 months. The authors recorded a high percentage of patency of the graft during check-up catheterization after a 6-month interval (94.7%), a low incidence of early complications of minor importance (2.5%), a low percentage of anginose complaints (7.9%) and reoperations (5%), while the lethality was not higher than in the control group (2.51%). The use of a graft from the rGEA is very suited for surgical treatment of IHD, in particular in patients of younger age groups and in reoperations. The authors discuss contraindications, the majority being only relative contraindications. The authors deal also with the preparatory surgical technique and the use of the graft. PMID- 8488424 TI - [The role and tasks of surgery within the transformation of the health care system]. PMID- 8488423 TI - [Autotransplantation of the spleen]. AB - The authors present a report on the autotransplantation of the damaged spleen by successful use of a tissue fibrin glue to fix thin lienal slices to the greater omentum. The new method was used in 8 men and 2 women, with the exception of one man in all patients after multiple injuries. From the total number two women died from sequelae of the injuries. Complications caused by replantation of the tissue were not observed. All the other patients survive and have no complaints associated with the loss of the spleen. The function of the transplant can be tested only by scintigraphy and laboratory examination. Other examinations by means of sonography, CT, X-ray of the stomach and irrigoscopy are not conclusive. The described method of replantation is suitable as it is simple and safe. In children orthotopic replantation is more suitable. PMID- 8488425 TI - [Functional reconstruction of urinary bladder exstrophy: long-term follow-up of urinary continence]. AB - The author followed up a group of seven patients 5 to 29 years after functional reconstruction without augmentation on account of classical exstrophy of the urinary bladder. The plastic operation to ensure continence was performed in 5 boys and 2 girls at the age of two and a half to 23 months, in six cases by the Young-Dees' method and in one patient by Leadbetter's method. Posterior iliac osteotomy was performed in two and an antireflux plastic operation was performed in four patients. In one patient a disruption of the plastic operation of the abdominal wall occurred on the fourth day after reconstruction. Continence was excellent in five patients and satisfactory in two. Among the many factors for urinary continence a plastic operation of the posterior urethra and neck of the bladder is most important as it creates the appropriate length of the continence zone and the adequate pressure on closure. In the discussion the author emphasizes the advantage to start with the reconstruction of the abdominal wall and bladder during the neonatal period and to proceed in stages. The functional closure of the bladder and its neck with the posterior urethra should be implemented after a minimal capacity of 60 ml has been attained. Augmentation enterocystoplasty is indicated on account of urinary incontinence as a secondary operation if the function of the urethra and neck of the bladder is satisfactory and achieved capacity is less than 100 ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488426 TI - [Breast carcinoma in women]. PMID- 8488427 TI - [Retrograde myocardial revascularization using a bypass into the cardiac vein]. AB - The authors submit a review of the surgical treatment of ischaemic heart disease, and based on data from the literature and their own experience, they evaluate the asset of so-called indirect revascularization operations under conditions when an aortocoronary bypass is impossible or has only a short-term effect due to the diffuse sclerotic affection of the coronary circulation. Special attention is paid to attempts of retrograde revascularization of the heart muscle by bypasses into the coronary veins. Because at present the possibility of indirect revascularization of the myocardium by a retrograde approach via the cardiac veins still remains a by far not yet resolved problem, the authors recommend for situations where the aortocoronary bypass is out of question a procedure making use of the advantages of a direct aortocoronary bypass and Vineberg's operation performed so as to relieve the blood flow through the sclerotic coronary artery beneath the anastomosis. In special situations also a sequential bypass could be considered with a side-to-side anastomosis into the artery and end-to-side into the appropriate vein. PMID- 8488428 TI - [Laparoscopic cholecystectomy: early results in the initial non-selected group of 50 surgical patients]. AB - Early results of an initial non-selected group of 50 laparoscopic cholecystectomies (mean hospitalization 3.5 days, 6% conversions, no serious complications, no revisions, morbidity due to minor complications 6.3% and saved costs of postoperative hospital treatment 44.6%) confirm that this operation is feasible, safe, preferred by patients and well tolerated economical definitive treatment of cholecystolithiasis. On these grounds it is becoming a method of first choice. The safety of patients is ensured by steady care of the surgeon and his adequate training according to generally accepted principles. PMID- 8488429 TI - Clinical anatomy: a new challenge. PMID- 8488430 TI - Anatomic basis of the physiopathology of the epicondylalgias: a study of the deep branch of the radial nerve. AB - Compression of the deep branch of the radial n. during its passage through Frohse's arcade in the supinator m. is one of the classical explanations advanced for epicondylalgia. The object of this study was to define the anatomy of the deep branch of the radial n. from its origin up to the origin of the branches to the lateral epicondylar mm. 34 upper limbs were dissected and three segments of the deep branch of the radial n. were distinguished: segment I, from its origin to its entry into the supinator m.; segment II, corresponding to its passage through the supinator m.; and segment III, extending from its exit from the supinator m. to the origin of the nn. to the lateral epicondylar mm. The lengths of these three segments were defined, as well as the level of division of the radial n. in relation to the joint-line, the thickness of the arcade of the supinator m., and the number of nerve branches to the supinator m. It was found that segment III is closely related to the radial head, around which it winds in supination and extension. The three nerve segments thus defined were studied separately microscopically for evidence of lesions. The results were as follows. Segment I: absence of any marked histologic lesions; segment II: marked fibrous thickening of the perineurium and the interstitial connective tissue, replacing certain nerve fibers; segment III: persistence of moderate interstitial fibrosis. These findings appeared constant in all the specimens examined. These results indicate that the deep branch of the radial n. is most affected during its passage through the supinator m.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488431 TI - Large inferior right hepatic vein. Clinical implications. AB - The right middle and inferior hepatic vv. are very frequent, indeed constant, but usually of small caliber. The presence of an extra-wide right inferior hepatic v., usually solitary, produces a variation in the venous drainage of the right lobe of the liver. The right inferior hepatic vv. reaching or exceeding a caliber of 0.5 cm were investigated in 125 anatomic liver specimens: 70 injection corrosion specimens, 32 formolised livers and frontal or frontal-oblique sections of the trunk made in 23 cadavers. The incidence of such vv. was estimated at 9% in the injection-corrosion specimens, 13% in the sections and 16% in the formolised livers. The incidence of these vv. in the literature varies from 10% to 24% according to the method used to demonstrate them. Usually, there is a balance between the right superior and inferior hepatic vv. Rarely, the right inferior hepatic v. predominates compared with the right superior hepatic v. The position of an extra-wide right inferior hepatic v. is constant, close to the visceral aspect of the liver. Its appropriate territory is segment VI, but it may encroach somewhat on adjacent segments. Clinically, the existence of an extrawide right inferior hepatic v. as detected by MRI and, especially, located by intraoperative ultrasonography, allows performance of a subtotal hepatectomy leaving only segment VI. In certain pathologic conditions, thanks to the development of anastomoses between the hepatic vv., an extra-wide right inferior hepatic v. may contribute to a compensatory circulation towards the right atrium. PMID- 8488432 TI - Origin of the internal thoracic artery and its relationship to the phrenic nerves. AB - The internal thoracic artery was studied because of its recent use in the revascularization of the myocardium in patients with coronary artery disease. The artery of 50 cadavers of adult individuals of either sex, whose age ranged from 20 to 84 years, was studied after neoprene latex injection. Its origin, relation to the phrenic nerve and origin of the pericardiacophrenic artery were investigated. The left and right phrenic nerves cross the artery anteriorly in 54% of the cases and posteriorly in 14%. The right nerve crosses the artery anteriorly and the left posteriorly in 22%, and the reverse occurs in 10%. The origin of the internal thoracic artery is much more frequent from the subclavian artery (80%) than from a common trunk with other arteries (20%). The pericardiacophrenic artery is a branch of the internal thoracic artery in 99% of the cases and the average distance between the origins of these two arteries is 3.9 +/- 1.3 cm. PMID- 8488433 TI - Anatomical study of five prenataly diagnosed sternopagus twins. AB - Among conjoined twins (1 out 50000 births), thoracopagus occurs most frequently and is generally lethal. Our anatomical study of five sets of sternopagus twins (3 female, 2 male) was performed to determine the ability of prenatal sonography to detect these anomalies. Autopsy in four cases revealed identical malformations: common sternum, single malformed heart, joined hepatic parenchyma, and a common small bowel leading to a cystic dilatation situated on the ileal segment at the end of the superior mesenteric artery. The diagnosis of conjoined twins was made in all cases by prenatal sonography at the mean time of 24.6 gestation weeks (range 19-34). The malformations detected by prenatal sonography were a single cardiac mass (all cases), joined hepatic parenchymas (3 cases), and an ileal cystic dilatation (1 case). Pregnancy was terminated in four cases. In one case cesarean delivery was performed, and the infants died 48 hours later. Prenatal sonography currently seems to be the best examination for diagnosis of sternopagus twins and the detection of lethal malformations thus allowing interruption of pregnancy. PMID- 8488434 TI - Relations between Meckel's cartilage and the morphogenesis of the mandible in the human embryo. AB - Based on a series of human embryos classified in stages, the authors studied the evolution of Meckel's cartilage in its ventral portion and its relations to the morphogenesis of the mandible. Three stages appeared particularly important: stage 16, appearance of Meckel's cartilage; stage 20, beginning of membranous ossification; and stage 23, end of the embryonic period (8th week). The primitive bony nodule which develops from the embryonic mesenchyme appears as a double bony layer forming a groove containing the neurovascular bundle, into which the dental lamina is also invaginated. PMID- 8488435 TI - A survey of different high resolution visualization modes of a volumetric object with applications. AB - In view of the variety of 3D representation techniques, a clinical study was carried out in order to evaluate their respective usefulness. It appears that a single technique cannot be claimed to be valid for all clinical situations and that a combination of representations brings more relevant information. Among the different techniques a clear delineation must be established between those which allow the accurate definition of landmarks (multiplanar reformation, surface representation), and those which do not (integral shading, reconstructed radiology). The main point is the possibility to recognize anatomical landmarks on these latter modes and to choose oblique cut planes in relation to them. Visualization quality is strongly dependent upon the acquisition protocol which must provide a spatial resolution as isotropic as possible. PMID- 8488436 TI - Ultrasonic assessment of the anatomy and function of the tongue. AB - The tongue is a complex muscular structure. Apart from its intrinsic strength, it has a major influence on the adjacent bony structures. Real time ultrasound appears to be the method of choice for assessing the topographic and functional anatomy. The examination was performed using an Acuson 128 scanner, with a 5 MHz probe, either a sector scanner (sagittal plane) or linear array probe (coronal plane). The scans were performed using the sub-hyoid approach, between the rami of the mandible. The images were stored on U-matic videotape. Thirty adult patients were included in the study population. The scan protocol consisted of an examination of the tongue at rest, a scan of the swallowing mechanism with and without a liquid bolus and a study of the posterior lingual positions (which show some anatomical variation). The intrinsic muscles of the tongue and the floor of the mouth could be identified on the "at rest" images. The lingual mass is the most important parameter and is opposed against the palate in order to propel a bolus during the swallowing mechanism. The mobility, shape and supporting structures of the tongue are variable depending on the nature of the bolus, the patient and the two imaging planes. Ultrasound is a simple and non-invasive method for the examination of the buccal cavity. The function of the posterior portion of the tongue must be taken into consideration prior to any treatment concerning the oral cavity. PMID- 8488437 TI - Anatomy of the acromial arch: correlation of anatomy and magnetic resonance imaging. AB - Based on a retrospective study of 179 MRI records covering four populations (patients presenting with impingement without known injury (n = 90), post traumatic shoulder pain (n = 28), instability or dislocation (n = 36) and controls (n = 25)), morphologic criteria are suggested to define presumedly normal arches and arches compatible with subacromial impingement. The subacromial arch is presumed normal or without impingement if the sagittal and frontal views show it to be parallel to the humeral head, and/or if there is a fatty layer interposed between the arch and the supraspinatus m. The arch is presumed "aggressive" or actually capable of giving rise to impingement if, in either the sagittal or frontal view, there is a zone of narrowing of the subacromial passage with an impression of the arch on the supraspinatus tendon or tendinous thinning at this level or just lateral to this narrowed zone. Based on these criteria, study of the 179 MRI records demonstrated a significant difference of distribution of the arches in the four populations. "Aggressive" arches were found in 45.5% of patients with impingement, 25% of patients with posttraumatic pain, 8.9% of patients with an acute or recurrent dislocation and 12% of controls. Conversely, a presumedly normal arch was found in 56% of the controls, 55% of patients with dislocation, 25% of posttraumatic painful shoulders and only 5.5% of patients with clinical impingement. Subacromial impingement may be due to the type 3 acromial dysplasia described by Bigliani or to a thickening of the coracoacromial ligament at its acromial attachment. This study was supplemented by 15 anatomic dissections which confirmed the regularity of attachment of the coracoacromial ligament at the inferior aspect of the acromion along its lateral border. PMID- 8488438 TI - Anomalous origin of the brachiocephalic vessels with right aortic arch and contralateral subclavian steal syndrome. AB - Anomalies of origin of the brachiocephalic vessels are uncommon. The authors report a new case of such an abnormality revealed by a subclavian steal syndrome. The angiographic study showed a right aortic arch with hypoplasia of the origin of the left subclavian a., which arose from the descending aorta, and a collateral cervical circulation derived from the left vertebral a. and the right subclavian a. PMID- 8488439 TI - Adaptation of facial architecture in the Toulouse deformity (23.10.92). PMID- 8488440 TI - Microsurgical anatomy of the ethmoid. AB - A description of the constant landmarks of the ethmoidal labyrinth is proposed, based on data from micro-dissection, endoscopy, computed tomography and histology in 12 subjects. In accord with surgical procedure, the identification of these landmarks follows the lateral orbital and superior cranio-frontal aspects. The uncinate process, ethmoidal bulla, middle nasal concha and their septal roots, and the upper wall of the ethmoidal labyrinth in continuity with that of the sphenoidal sinus, form the definitive landmarks for endonasal ethmoidectomy under endoscopic monitoring. PMID- 8488441 TI - Fertility following excision of a symptomatic craniopharyngioma during pregnancy: case report. AB - A 27-year-old woman in the second trimester of pregnancy presented with bitemporal hemianopsia. Total resection of a craniopharyngioma restored normal vision, and she delivered a normal infant at term. Permanent hormonal replacement therapy was not needed. Subsequent spontaneous pregnancy and delivery indicate that fertility was preserved. Literature review shows this case to be unique. Even with new developments in stereotactic radiotherapy, total excision remains a potentially achievable surgical goal. PMID- 8488442 TI - Recurrence of symptomatic Rathke's cleft cyst: a case report. AB - A 65-year-old man presented with bitemporal hemianopsia. He had undergone frontal craniotomy for a Rathke's cleft cyst associated with narrowed visual field 8 years earlier. His vision had returned to normal soon after surgery and he remained asymptomatic until the present complaint. Neurodiagnostic imaging revealed a recurrence of the intrasellar cyst extending into the suprasellar cistern. His vision improved rapidly after a second surgery. The histological findings were the same as those of the previous operation; the cyst wall was composed of a single layer of ciliated columnar epithelium resting on a collagenous connective tissue stroma. PMID- 8488443 TI - Management of low-risk head injuries in an entire area: results of an 18-month survey. AB - All patients admitted following a minor head injury (GCS is without neurological deficits) during an 18 month period in an entire area were submitted to the same diagnostic and therapeutic protocol. Adult patients were x rayed and in the cases with skull fracture (even asymptomatic), a computed tomographic (CT) scan was performed. Children (below the age of 14) did not routinely receive skull X-rays but were admitted to one of the five regional hospitals where a CT scanner was available 24 hours per day. Neuroradiologic investigations (carried out in over 600 patients) showed posttraumatic lesions in 201 cases; 113 of these patients were transferred to the neurosurgical center. There were 49 patients with extradural hematomas, 41 with brain contusions, 17 with depressed skull fractures, and six with subdural hematomas. Of these 113, 40 patients were operated on (mainly extradural hematomas); surgical indications were based on appearance of clinical deterioration, lesion volume, presence of midline shift, and/or compressed third ventricle and basal cisterns. In eight cases there was a clinical deterioration to a GCS of 13 or less; in all of these patients, the CT diagnosis (and transfer to a neurosurgical center, preceded the onset of deterioration. All patients admitted to such a center had a good outcome, but a survey of deaths related to head injury in the area revealed two fatalities following minor head injury. The only avoidable death was a patient with multiple brain contusions who developed sudden brain swelling on day 12 post-trauma. We conclude that, even if management mortality is not zero, our protocol is sufficiently safe for the treatment of minor head injury. PMID- 8488444 TI - Severe subarachnoid hemorrhage during transsphenoidal surgery for pituitary adenoma. AB - There are many reports about complications of transphenoidal surgery for pituitary adenomas. We report a patient who suffered severe subarachnoid hemorrhage due to an indirect injury of the intradural internal carotid artery during or immediately after transsphenoidal surgery for pituitary adenoma. An autopsy suggested that a small branch of the intradural internal carotid artery was strongly adherent to the suprasellar portion of the tumor capsule and its avulsion from the internal carotid artery might have been caused as the capsule fell down during the intracapsular removal of the tumor. In a case of pituitary adenoma operated by the transsphenoidal approach the possibility of subarachnoid hemorrhage due to this type of arterial injury, though rare, should be kept in mind. PMID- 8488445 TI - Bilateral synovial cysts of the thoracic spine: a case report. AB - We report a case of bilateral synovial cysts of the thoracic spine. The patient presented with progressive, lower-extremity weakness and hypesthesia, culminating in complete paraplegia. This rare lesion should be considered when confronted with a patient with thoracic cord compression. PMID- 8488446 TI - Villaret's syndrome: a report of two cases. AB - The syndrome resulting from lesions of the lower four cranial nerves (CN) and the cervical sympathetic chain is known as Villaret's syndrome. We report two cases of the syndrome and emphasize the localizing value of this constellation of signs. The second case is unusual because involvement of the cervical sympathetic chain produced sympathetic overactivity, instead of the usual sympathectomy effect. Increased sympathetic outflow expressed as pupillary dilation, widened palpebral fissure, and facial sweating (the Claude Bernard syndrome) usually occurs as an early manifestation of apical thoracic tumors and has not been previously associated with Villaret's syndrome. PMID- 8488447 TI - Primary malignant non-Hodgkin's lymphoma of cranial vault: a case report. AB - Primary cranial vault non-Hodgkin's lymphomas are rare and only four such cases are described in the literature. A 65-year-old woman presented with focal neurological deficits and a subcutaneous scalp lump. Computed tomography (CT) scan showed a left parietal cranial vault lesion with soft tissue scalp swelling and underlying intracranial extra axial mass mimicking a meningioma. Histology showed features of a typical B-cell non-Hodgkin's lymphoma, there was no systemic involvement. The characteristic CT findings of this lesion are described and relevant literature is reviewed. We are reporting this case because of its rare occurrence. A diagnosis of primary lymphoma of the skull vault should always be considered in the differential diagnosis when such a lesion is encountered. PMID- 8488448 TI - Review of 140 patients with brain abscess. AB - There were 140 cases of brain abscess treated between 1980 (when CT scanning became available) and June 1991. These arose by spread of a contiguous area of infection in 37%, and from another identified cause in 22%; the origin was undetermined in 41%. There were multiple abscesses in 11%. The abscess was < 2 cm in diameter in 21%. In two-thirds of the patients, the intracranial pressure was raised, there were localizing neurologic signs in 33%, and in 28% there were epileptic seizures. The computed tomographic (CT) feature of an abscess in the capsular stage was a thin, regular, and uniform, ring-like enhancement. In the cerebritis stage, nine out of 17 patients showed a uniform enhancement throughout the lesion. Since 1989, 14 cases have been investigated with magnetic resonance imaging (MRI). In 11, the abscess was in the capsular stage. In both T1- and T2 weighted images, the abscess and the surrounding inflammatory area were well demonstrated, and with T2-weighting, the capsule showed a low-intensity signal clearly. In the three abscesses in the cerebritis stage, there was a uniform abnormality with indistinct margins between the abscess, inflammatory edema, and surrounding grey and white matter. All cases received a combination of wide spectrum antibiotics before the organism was identified; and later the medication was administered according to bacteriologic indication of the organism of 112 cases, organisms were identified in 71%, with anaerobic organisms occurring in 30% of these. In 127 cases, surgical treatment was used: either repeated aspiration, excision or both. We treated 13 cases that had small, early, or multiple abscesses with antibiotics only. The mortality with surgical treatment was 7.9%, and no case treated conservatively died. PMID- 8488450 TI - Isolated fourth ventricle in neurocysticercosis: pathophysiology, diagnosis, and treatment. AB - Four cases of isolated fourth ventricle in neurocysticerocosis are reported (three after ventriculoperitoneal shunting, and one after hydrocephalus without shunting). Diagnosis was made based on computed tomography (CT) and/or CT cisternogram/ventriculogram. Three patients underwent fourth ventricle drainage (two died and the third remains well). The fourth patient refused surgical treatment and continues to have severe ataxia. Diagnosis, pathophysiology, and treatment of this entity in neurocysticercosis are discussed. PMID- 8488449 TI - Time course of energy perturbation after compression trauma to the spinal cord: an experimental study in the rat using microdialysis. AB - Changes occurring in the extracellular fluid (ECF) concentration of energy related metabolites were investigated in a well-characterized model of compression trauma to the spinal cord. Microdialysis probes were inserted into exposed grey matter of the dorsal horn at the level of Th 7-8, and perfused with mock cerebrospinal fluid. The trauma was produced 2 hours later by compression of the cord with a 9-, 35-, or 50-g load for 5 min. Microdialysis samples (10-minute fractions) were collected for another 2 hours following decompression. The trauma was associated with an accumulation of lactate, inosine, and hypoxanthine, and an increase in the lactate/pyruvate ratio in the ECF, indicating a profound disturbance in energy metabolism. These changes were related to the severity of spinal cord injury as well as to the spinal cord blood flow (SCBF) reductions and neurological deteriorations previously determined. Following decompression, all ECF metabolites normalized within 20-40 min after mild (9 g) to moderate (35 g) trauma. After severe trauma (50 g), resulting in complete ischemia during compression, followed by irreversible paraplegia, there was a partial recovery of ECF inosine and hypoxanthine, whereas the increase in lactate and the lactate/pyruvate ratio persisted. The results suggest that penumbra conditions prevail during the early posttraumatic period when the degree of trauma results in severe neurological deterioration and that ECF lactate levels in the spinal cord is a sensitive indicator of secondary ischemia after compression injury. PMID- 8488451 TI - Comments on specialty site visits by the Residency Review Committee for Neurological Surgery. PMID- 8488452 TI - Extravasation of contrast medium from the lenticulostriate artery following local intracarotid fibrinolysis. AB - Two patients with acute embolic occlusion of the intracranial internal carotid artery and the lenticulostriate arteries were treated by local intraarterial fibrinolysis using tissue plasminogen activator. Although fibrinolysis started within 2.5 hours from the ictus, extravasation of the contrast medium from the lenticulostriate arteries occurred in the region of the basal ganglia. Local intraarterial fibrinolysis for acute embolic occlusion of the internal carotid artery may be a high-risk therapeutic intervention even within the ultra-acute stage, especially when the lenticulostriate arteries are occluded by an embolus. PMID- 8488453 TI - Nonaneurysmal subarachnoid hemorrhage: prevalence of perimesencephalic hemorrhage in a consecutive series. AB - The perimesencephalic type of nonaneurysmal subarachnoid hemorrhage (SAH) is a recently described clinical and radiological entity, with a good outcome. We carried out a retrospective analysis of 294 patients with subarachnoid hemorrhage, of whom 62 had a negative four-vessel angiography. We identified 20 cases with the typical computed tomographic (CT) pattern of perimesencephalic hemorrhage, in whom the prognosis was invariably good. However, five cases of aneurysmal subarachnoid hemorrhage had a more or less similar CT appearance: the diagnosis cannot be made on the CT image only and angiography remains mandatory. The use of bed rest, antifibrinolytics, and calcium antagonists is discussed. PMID- 8488454 TI - Traumatic atlanto-occipital dislocation with survival: a case report and review of the literature. AB - The number of patients who have survived traumatic atlanto-occipital dislocation, the usual outcome of which is death from brain stem transection, has increased in the past two decades due to improvements in on-scene resuscitation and transportation. This case of survival after traumatic atlanto-occipital dislocation is of interest because the patient had a complete neurologic recovery and a magnetic resonance imaging (MRI) study was obtained to confirm the diagnosis and rule out associated injuries. PMID- 8488455 TI - Intracranial cryosurgery in a canine model: a pilot study. PMID- 8488456 TI - Cranial fasciitis of childhood: a case report. PMID- 8488457 TI - [Simultaneous radiochemotherapy]. AB - Simultaneous radiochemotherapy (RCT) means the simultaneous application of radiotherapy and chemotherapy. The major objective of this approach is the improvement of local control. On the cellular level, three types of interactions may be distinguished: additivity, synergism, and sensibilization. The main type of interaction seems to be a simple additive effect. The clinical effect of a simultaneous chemotherapy depends mainly on the cytotoxic action of the drug itself and not on radiosensibilization. Therefore, effective chemotherapeutic drugs are to be delivered in cytotoxic dosages in RCT protocols. Compromises in radiotherapy as the main modality should be avoided. Recent clinical data have shown that simultaneous radiochemotherapy may yield high remission rates in a number of tumor entities (e. g. anal cancer, bladder cancer, head and neck cancer). This seems to improve local control as compared to radiotherapy alone. In some tumors (e. g. head and neck, esophagus), survival may be improved also. However, several questions require future detailed clinical trials. These questions include the value of simultaneous radiochemotherapy compared to optimal fractionation schemes, the clear definition of subgroups of patients with benefit by radiochemotherapy and the optimal dose intensity of cytotoxic drugs. PMID- 8488458 TI - [Medulloblastomas--the results after postoperative radiotherapy with and without adjuvant chemotherapy]. AB - Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma were treated at the authors' institutions. After aggressive surgical resection 39/40 (98%) received craniospinal radiation therapy with a local boost to the posterior fossa and other macroscopically involved areas. A group of 29 patients was treated with adjuvant chemotherapy. The five-year actuarial survival and event free survival were 75% and 65%, respectively. Survival was significantly better for patients treated after 1981 as compared to those treated between 1975 and 1980 (p = .02). Younger age (two to four years) was associated with a better prognosis (p = .02). The extend of resection, Chang-stage, radiation dose to posterior fossa and the use of chemotherapy did not significantly impact on survival and relapse-free survival. PMID- 8488459 TI - [The clinical picture and therapy of aggressive fibromatosis (desmoids)]. AB - Desmoid tumors are accounted among histologically benign soft tissue tumors. Though metastases do not occur the clinical course of the disease with their tendency to grow locally aggressive and to relapse after curative intended surgery is similar to sarcomas. After surgical excision adjuvant therapy of desmoid tumors is necessary in such cases, where a radical excision with a wide margin is not possible, or must be doubted or after the surgical excision of a locally recurrent tumor. Radiation doses of 50 to 60 Gy reduce the risk of local recurrence of desmoid tumors to 18%. In such cases, where surgery and radiotherapy have been leading to incomplete responses, systemic therapy with hormones (tamoxifen or progesterone), with alkylating agents (e. g. ifosfamide) or with prostaglandin antagonists (indomethacin) is possible. The published data on therapeutic responses to the treatment of desmoid tumors are scarce. We are reporting on seven of our own cases, treated with surgery and radiotherapy (four) or with a combination of surgery, radiotherapy, hormones and chemotherapy (three). PMID- 8488460 TI - [Is lymphography still relevant in seminoma?]. AB - In the radiotherapist's point of view lymphography and computed tomography scan compete for staging and therapy planning of testicular seminoma. We investigated whether lymphogram can be replaced by computed tomography scan. 114 patients with histologically confirmed seminoma of the testis were treated by radiotherapy at the Nurnberg Community Hospital (n = 65) and the University of Erlangen (n = 49) from 1978 through 1991. Radiological staging included both computed tomography scan and lymphography in all cases. The results of both methods were similar in 79%. Computed tomography scan led to an upstaging in 4% while lymphography was negative. 17% of the patients showed negative results considering computed tomography scan while lymphogram was positive. In accordance with these data treatment portals or doses were altered in 21%. Using the M.D. Anderson Hospital clinical staging system a stage IIa (micrometastasis < 2 cm) is not safely identified by computed tomography scan. Just lymphography can safely identify a stage IIa patient. On the other hand, lymphography shows a very high amount of false positive interpretations. However, two conclusions are made: 1. Using a conventional technic (radiation of para-aortal and ipsilateral iliac region, dose about 30 Gy HD) lymphogram can be superseded by computed tomography scan. 2. In the case of reducing treatment volume and/or dose lymphogram should be added to computed tomography scan. PMID- 8488461 TI - Role of total body irradiation as based on the comparison of preparation regimens for allogeneic bone marrow transplantation for acute leukemia in first complete remission. AB - The role of total body irradiation (TBI) for allogeneic bone marrow transplantation (BMT) for acute leukemia in first complete remission was reevaluated in this study. From Japanese BMT Registry, data of 123 acute leukemia patients in first complete remission who underwent allogeneic bone marrow transplantation in 22 hospitals between 1988 and 1990 were available for the present comparative study of preparation regimens with or without total body irradiation. Two-year survivals were 77% and 51% in the TBI containing regimen group and in the non-TBI regimen group, respectively (p = 0.0010). Corresponding two-year relapse rates were 16% and 37%, respectively (p = 0.0197). Corresponding probabilities of developing interstitial pneumonitis were 21% and 24%, respectively (p = 0.8127). The analysis of causes of death indicated that non-TBI regimen increased the incidence of septicemia and lethal organ failures, such as liver, heart, lung and other multiple sites. It was emphasized that an additional role of total body irradiation was to disperse the treatment-related toxicity in allogeneic bone marrow transplantation for acute leukemia. PMID- 8488462 TI - Influence of blood storage after in vitro exposure on the yield of micronuclei observed in human lymphocytes. AB - In a cooperative study, four laboratories evaluated the micronucleus test in irradiated and non-irradiated lymphocytes with respect to time of storage, the difference between X-ray and gamma exposure and inter-observer variance. The results were compared with parallel studies on dicentric aberrations. No significant differences between laboratories, with respect to storage time or between gamma and X-irradiation were observed for micronuclei and dicentrics using analysis of variance. However, micronuclei are not suitable for an assessment of exposure inhomogeneity because of a significant overdispersion already in controls and homogeneously irradiated samples. PMID- 8488463 TI - Free radicals and other reactive oxygen metabolites: clinical relevance and the therapeutic efficacy of antioxidant therapy. AB - As in any new field, justifiable enthusiasm for the potential for antioxidant therapy has led to hyperbole, hastily designed, poorly conceived clinical trials, and premature reporting of uncontrolled, anecdotal indicators of efficacy that have not held up when subjected to close scrutiny or more careful, controlled trial design. This tendency has been augmented by strong pressure for early positive results from a few, but not most, members of the pharmaceutical industry and by a few clinicians in highly competitive fields who were anxious not to be left behind. The sobering reality of negative or, even worse, indeterminate clinical trials has culled the field and educated those that remain. As a result, we are beginning to see the publication of quite promising results from large, well-controlled, carefully designed clinical studies, many, but not all, of which are quite promising. This has been associated with a much better understanding of the basic mechanism of free radical-mediated human disease, without which further substantial progress would be quite limited. Because the manipulation of oxidant mediated tissue injury represents treating disease at its most basic level, the therapeutic potential of this approach remains not only promising but exciting. PMID- 8488464 TI - Healing of the stapled stomach in bariatric operations. AB - Breakdown of the in-continuity gastric staple line after gastroplasty and gastric bypass is frequently associated with either complications or unsatisfactory weight loss. Although there is wide variation in the reported incidence of stale line disruption after gastric bariatric operations, this complication is most frequently recognized by surgeons who routinely examine the integrity of the staple line at 12 months or more after operation. Upper gastrointestinal contrast studies are more sensitive than upper endoscopy in detecting small defects in the stapled gastric partition. The stomach should be routinely divided in patients who require reoperation for late staple-line disruption. This complication could be prevented by routine transection of the stomach at the initial gastric restrictive operation. PMID- 8488465 TI - Rationing surgery: rules or constraints? AB - BACKGROUND: As U.S. health care expenditures climb, the need to set limits on surgery is becoming more generally accepted. If limits are necessary, how should they be established and by whom? This article considers two fundamental approaches, rules and constraints. RESULTS: With rules, payers or policymakers ration care by prioritizing and then restricting specific procedures. Although they have the advantage of explicitness, rules based on treatment prioritization are limited by patient heterogeneity and the lack of outcomes data necessary to rank many procedures. Rules are unambiguous and free the surgeon from the obligation to set limits, but they do not accommodate clinical judgment or patient preferences. With constraints, limits are set on surgical resources (e.g., the number and distribution of surgeons), but individual surgeons determine which procedures are provided to which patients. Although constraints are more feasible than rules, it is difficult to establish an "adequate" supply of surgical resources and to ensure that limits set by the individual surgeon are based on treatment efficacy. While preserving clinical autonomy, constraints require the surgeon to assume the responsibility of rationing care. CONCLUSIONS: Surgeons should consider carefully the approach to rationing that best serves their professional interests, their patients, and society. PMID- 8488466 TI - Submucosal tumors of the stomach: a study of 100 operative cases. AB - BACKGROUND: Mass screening for gastric cancer has been established in Japan, and asymptomatic submucosal tumors are often detected. This retrospective study was made to evaluate the proper surgical management of malignant submucosal tumors of the stomach. METHODS: One hundred submucosal tumors of the stomach were surgically resected, irrespective of symptoms and size. Up to 45% of these tumors, including 44 myogenic lesions, 23 non-Hodgkin's lymphomas, and 11 schwannomas, proved malignant. Myogenic sarcomas were classified in low and high grades according to mitotic rates, cellularity, and pleomorphism. RESULTS: Thirty five of 55 benign tumors and four of nine low-grade sarcomas underwent enucleation only, without recurrence. The remaining five low-grade and 11 high grade sarcomas were treated by radical gastrectomy; the 5-year survival was 100% for the former and 80% for the latter. Eighteen patients with lymphomas underwent total or subtotal gastrectomy, and three patients underwent noncurative resection; the 5-year survival rates were 54.2% and 0%, respectively, with a clear significant difference (p < 0.001). Adjuvant chemotherapy was significantly superior to surgery alone (p < 0.05). Other factors did not affect survival of lymphoma. CONCLUSIONS: With these observations, we believe that following the patients with submucosal tumor without surgery is not reasonable. Enucleation will suffice for low-grade sarcomas and benign tumors; high-grade sarcomas can be well treated by gastrectomy. Total or subtotal gastrectomy with systematic lymph node dissection when performed for cure can provide good results for resectable lymphomas. PMID- 8488467 TI - Patterns of lung involvement by malignant lymphoma. AB - BACKGROUND: Recent evidence has suggested that the anatomic distribution of malignant lymphomas may reflect important differences in biologic behavior. To determine if the anatomic distribution of malignant lymphomas in the lung correlated with the disease course, we examined the pattern of lung involvement in patients with Hodgkin's and non-Hodgkin's lymphomas. METHODS: We reviewed the medical records of 651 patients with a diagnosis of malignant lymphoma and identified 54 patients with histologically documented lung involvement. Based on radiologic and surgical findings, these patients had lung involvement characterized as either (1) bronchovascular-lymphangitic, (2) nodular, or (3) alveolar. The pattern of lung involvement was correlated with clinical manifestations and disease course. RESULTS: Distinct clinical courses were associated with these three patterns of lung involvement. In contrast, traditional histopathologic classification did not correlated with the pattern of lung involvement was a poor prognostic factor and was associated with a median survival of 12 1/2 months. Pleural effusions eventually developed in 24 patients and were associated with a median survival of only 3 months. CONCLUSIONS: These findings suggest that the anatomic pattern of lung involvement is a measure of biologic behavior and may be a useful variable in the staging of patients with malignant lymphoma. PMID- 8488468 TI - Reconstruction of the thoracic esophagus, with extended jejunum used as a substitute, with the aid of microvascular anastomosis. AB - BACKGROUND: After radical ablation of tumors, colon or jejunum is pulled up for reconstruction of the thoracic esophagus when stomach is unusable. However, esophagocolonic or esophagojejunal anastomotic leak is relatively frequent because of the potential for vascular insufficiency of conduit extended upward. METHODS: To overcome this disadvantage, 14 consecutive patients with esophageal or gastric carcinomas whose stomachs were unusable were subjected to thoracoesophageal reconstruction through upward extension of the jejunum with microvascular anastomosis. Jejunal vessels were used as graft vessels, and internal thoracic vessels were used as recipient vessels. If needed, arcade vessels were severed to ease extension. RESULTS: All extended jejunums survived, and there were no operative deaths. Two of four initial series of patients, whose arcade vessels were not severed despite undue tension at the anastomotic site, had esophagojejunal anastomotic leaks that healed spontaneously. CONCLUSIONS: Some clinical functional problems still exist, but we believe this a safe and useful method for reconstruction of the esophagus where stomach cannot be used. PMID- 8488469 TI - Gastric intramucosal acidosis in patients with chronic kidney failure. AB - BACKGROUND: Patients with chronic kidney failure have an increased incidence of gastrointestinal complications, particularly bleeding from the stomach. Diminished mucosal blood flow is thought to be an important etiologic factor for such bleeding. METHODS: Eleven patients with kidney failure on maintenance dialysis underwent placement of a gastric tonometer for the determination of gastric intramucosal pH (pHi) before and during dialysis. The arterial pH (pHa), calculated pHi, and pHa-pHi differences were compared with the results in a control group of seven normal volunteers. RESULTS: The patients with chronic kidney failure had a mean (+/- SD) pHa (7.36 +/- 0.04) similar to that found in seven control subjects (7.37 +/- 0.04). However, the gastric mucosal pH in the patients on dialysis (7.20 +/- 0.17) was lower than in the seven control subjects (7.38 +/- 0.06) (p < 0.01). A gastric mucosal pH thought to be predictive of either bleeding from stress ulceration (pHi < 7.32) or mucosal ischemia (pHi-pHa difference > 0.13) was found in nine (82%) of the patients with kidney failure and in only one (14%) of the control subjects (p < 0.001). CONCLUSIONS: This new preliminary finding suggests that the high incidence of gastric bleeding in chronic kidney failure may be related to mucosal ischemia. PMID- 8488470 TI - Comparative cardiopulmonary effects of carbon dioxide versus helium pneumoperitoneum. AB - The recent surge in enthusiasm for laparoscopic surgery has created concern that abdominal insufflation with carbon dioxide produces a respiratory acidosis. This may be because of both transperitoneal gas absorption and impaired ventilation with increased dead space from elevated intraabdominal pressure. To examine the relative contributions of these factors, we developed an animal model of surgical pneumoperitoneum that evaluated the cardiorespiratory effects of abdominal insufflation. Helium was chosen as an alternative to CO2 because it is both chemically and biologically inert. Carbon dioxide absorption during CO2 pneumoperitoneum caused arterial PCO2 to increase from 41.3 +/- 3.0 to a maximum of 58.3 +/- 4.0 mm Hg, with pH descending from 7.46 +/- 0.02 to a nadir of 7.31 +/- 0.02 (p < 0.05). Pulmonary artery pressure increased to twice baseline levels during CO2 insufflation (p < 0.05). Helium did not cause hypercarbia, acidemia, or pulmonary hypertension despite insufflation under identical conditions. These results indicate that transperitoneal absorption of CO2, not increased dead space, is responsible for the respiratory acidosis observed. Helium merits further study as an agent to induce pneumoperitoneum, especially when concerns of underlying acidosis or impaired gas exchange are present. PMID- 8488471 TI - Medial pancreatectomy for tumors of the neck of the pancreas. AB - BACKGROUND: The surgical treatment of benign tumors of the pancreas usually consists of enucleation or formal pancreatectomy. Nonetheless, enucleation is not always feasible, and extended pancreatectomies may result in impaired endocrine and exocrine function. METHODS: For these reasons we proposed a limited resection centered on the neck of the pancreas with complete excision of the tumor. The cephalic section was sutured, and a Roux-en-Y jejunal loop was anastomosed to the distal section of the pancreas. Fourteen patients were operated on by this technique. The tumors were mainly cystadenomas (n = 6) and endocrine tumors (n = 4). The other lesions were one epithelial cyst, one necrotic pseudocyst, one Castleman disease, and one cystadenocarcinoma diagnosed after surgery on histologic examination. RESULTS: No patients died. Two patients underwent reoperation: one for a postoperative acute pancreatitis and one for a pancreatic fistula. All patients were followed up from 4 months to 8 years. No patients had exocrine insufficiency or diabetes mellitus. CONCLUSIONS: Medial pancreatectomy does not carry a higher operative risk than formal pancreatectomy and avoids extensive pancreatic resection when enucleation is not feasible. PMID- 8488472 TI - Generation of cytotoxic T lymphocytes from peripheral blood. AB - BACKGROUND: Cytotoxic T lymphocytes (CTL) have been shown to be useful for adoptive immunotherapy in malignancy. Traditional sources for CTL, such as tumor infiltrating lymphocytes, have limitations. It would therefore be useful to develop a method of generating antitumor CTL from a renewable source such as peripheral blood. METHODS: DBA/2 mice were injected intradermally in the abdominal wall with the murine tumor PHS-5 and killed 14 days later. Peripheral blood lymphocytes were harvested and cultured with 20 units/ml interleukin-2 and autologous tumor-stimulator cells treated with mitomycin C. Cultures were split when greater than 2 x 10(6) cells/well, fed every 3 days and stimulated weekly. RESULTS: Lymphocytes expanded greater than 130,000-fold during 8 weeks. Specific cytotoxicity was shown with 51Cr release assay. Withdrawal of repeated stimulation with autologous tumor resulted in failure of cells to expand in culture and loss of cytotoxicity. In vivo administration showed marked reduction of 10-day liver metastases, indicating therapeutic efficacy. CONCLUSIONS: These data demonstrate a successful animal model of adoptive immunotherapy with CTL generated from peripheral blood lymphocytes. PMID- 8488473 TI - Clinical evaluation of upper mediastinal dissection for differentiated thyroid carcinoma. AB - BACKGROUND: An extensive upper mediastinal dissection in advanced differentiated thyroid carcinoma is occasionally required. This investigation was undertaken to clarify the indications for mediastinal lymph node dissection and the route of upper mediastinal metastases. METHODS: Twenty-one patients with differentiated thyroid cancer, who underwent their first radical operations with mediastinal dissection through a partial midline sternotomy, were enrolled in this study. Of 21 patients, 10 (48%) were found to have mediastinal lymph node metastases. RESULTS: The tumor size in the group with metastatic disease was much bigger than that in the group without metastatic disease. Histologic type and age were similar between the two groups. The extent of cervical lymph node metastases was more significant in the group with metastatic disease; in particular, all 10 patients showed more than two metastatic nodes along the internal jugular vein of the tumor-free side. CONCLUSIONS: This study indicates that metastases to the internal jugular chain on the side contralateral to the primary tumor would be an extremely important factor for indication of extensive upper mediastinal lymph node dissection after median partial sternotomy in patients with differentiated thyroid carcinoma. PMID- 8488474 TI - Intestinal fatty acid binding protein in serum and urine reflects early ischemic injury to the small bowel. AB - BACKGROUND: Intestinal fatty acid binding protein (I-FABP) is a 15 kd protein that constitutes 2% to 3% of enterocyte protein. Normally I-FABP is undetectable in serum. The purpose of this study was to determine whether I-FABP could be detected in peripheral serum and/or urine early in the evolution of intestinal ischemic injury. METHODS: I-FABP and two putative biochemical markers of mesenteric ischemia, hexosaminidase and lactate dehydrogenase, were quantitated in the serum of rats subjected to mesenteric ischemia produced by: (1) 0.5 hours, 1 hour, or 3 hours of superior mesenteric artery (SMA) occlusion followed by reperfusion; (2) 1 hour of mesenteric occlusion to a 10 cm segment of jejunum followed by reperfusion; and (3) arterial ligation to a 10 cm segment of jejunum without reperfusion. I-FABP was also quantitated in the urine and intestinal mucosa of these animals. RESULTS: The baseline serum I-FABP level was < or = 4.0 ng/ml in all animals. In control animals, I-FABP remained unchanged throughout the experiment. In the ischemia/reperfusion groups, I-FABP immediately appeared in the serum on reperfusion. With segmental arterial ligation, I-FABP was detected in the serum within 15 minutes. Urinary content of I-FABP rose 60 minutes after its initial appearance in the serum, and its elimination paralleled serum I-FABP levels. Serum hexosaminidase and lactate dehydrogenase levels only rose after 3 hours of SMA occlusion with reperfusion. One hour of SMA occlusion and reperfusion resulted in only mild to moderate mucosal injury, whereas 3 hours of SMA ischemia with reperfusion produced areas of transmural necrosis. CONCLUSIONS: I-FABP is released into the peripheral circulation after reversible intestinal ischemic injury and has potential as a biochemical marker to facilitate the early detection of mesenteric ischemia. PMID- 8488475 TI - Regulation of small intestinal glutamine transport by epidermal growth factor. AB - BACKGROUND: Epidermal growth factor (EGF) stimulates cell replication and increases DNA content of the small intestine, but its effects on mucosal amino acid transport are unknown. METHODS: To investigate these effects, we treated adult rats with vehicle or EGF (10 micrograms/100 gm body weight subcutaneously every 8 hours for three doses). Jejunal brush border membrane vesicles (BBMVs) from each group were prepared by Mg++ aggregation/differential centrifugation. BBMVs were enriched fifteen-fold in alkaline phosphatase, indicating BBMV purity. Transport of 3H-glutamine and 3H-alanine was studied by a rapid mixing filtration technique. Uptakes were primarily Na+ dependent, occurred in an osmotically active space, exhibited classic overshoots, and had similar 2-hour equilibrium values. RESULTS: Glutamine transport by BBMVs more than doubled in rats treated with EGF (16.4 +/- 0.1 pmol glutamine/mg protein/10 sec in EGF vs 7.1 +/- 0.5 pmol glutamine/mg protein/10 sec in controls; p < 0.001). Kinetic studies of the glutamine transporter showed that the increase in transport was the result of a 70% increase in maximal transport velocity (total maximum glutamine uptake = 193 +/- 8 pmol glutamine/mg protein/10 sec in EGF vs 114 +/- 7 pmol glutamine/mg protein/10 sec in controls; p < 0.0001 with no change in transporter affinity (transporter affinity = 224 +/- 6 mumol/L in EGF vs 242 +/- 37 mumol/L in controls; difference, not significant). Alanine uptake by BBMVs was also increased with EGF administration (10.2 +/- 2.0 pmol alanine/mg protein/10 sec in EGF vs 4.5 +/- 0.5 pmol alanine/mg protein/10 sec in controls; p < 0.005). Simultaneously, glucose transport was decreased by 50% in EGF-treated rats, indicating that the Na(+)-dependent glucose cotransporter is regulated independently from and opposite to amino acid transporters. CONCLUSIONS: We conclude that EGF up-regulates amino acid transport activity in jejunal BBMVs, an event that is most likely caused by an increase in de novo biosynthesis of transporter protein. The increase in amino acid uptake not only may support de novo protein synthesis but, in the case of glutamine, also may be required for energy production and nucleotide biosynthesis. PMID- 8488476 TI - Effects of sodium valproate on various intestinal motor functions after ileal J pouch-anal anastomosis. AB - BACKGROUND: We investigate the effects of sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, on the clinico-physiologic state after ileoanal anastomosis. METHODS: Twelve patients (five with ulcerative colitis and seven with familial adenomatous polyposis coli) were studied in a placebo-controlled trial. RESULTS: Placebo had no effect, but valproate increased the resting anal pressure by 22.4% and the maximum tolerable pouch volume by 20.7%. It also prolonged pouch emptying by 47.3%, with an associated improvement in stool frequency and incontinence. These results suggested that valproate improved both reservoir continence and sphincter continence. CONCLUSIONS: Only minimal side effects were noted, so the administration of sodium valproate appears to be a safe and useful adjunct for patients with ileoanal anastomosis in the early postoperative period. PMID- 8488477 TI - Epidermal growth factor limits structural alterations in gastrointestinal tissues and decreases bacterial translocation in burned mice. AB - BACKGROUND: Burn injury produces acute gastrointestinal derangements that may predispose to bacterial translocation (BT). We studied effects of recombinant human epidermal growth factor (r-HuEGF), a gastrointestinal trophic hormone, on gastrointestinal alterations and BT after murine burn injury. METHODS: r-HuEGF was administered 1 and 12 hours after burn injury in a dose of 4 micrograms per animal subcutaneously after 25% and 32% total body surface area (TBSA) scald burn. Small bowel and gastric weight and histologic factors were studied, and BT was measured by culturing mesenteric lymph nodes. RESULTS: Mice treated with r HuEGF maintained gastric and small intestine weight measured 24 hours after burn injury, and ileal mucosal height was preserved, whereas burned-untreated mice lost organ weight and mucosal height. BT was decreased significantly in mice with 32% TBSA burn injury treated with r-HuEGF after injury (burn, 64.2% of animals had BT; burn-r-HuEGF, 34.6% had BT; p < 0.05). After 25% TBSA burn injury, BT was also decreased in r-HuEGF-treated animals (burn, 31.4% of animals had BT; burn-r HuEGF, 14.3% had BT), but the difference was not statistically significant (p < 0.1). CONCLUSIONS: r-HuEGF improves intestinal and gastric structure in mice 24 hours after burn injury and decreases BT after 32% TBSA burn injury. PMID- 8488478 TI - Successful treatment by simultaneous hepatic venoplasty and cavoplasty for Budd Chiari syndrome with obstruction of retrohepatic inferior vena cava. AB - BACKGROUND: Various surgical procedures for treating chronic Budd-Chiari syndrome have been established, but none are adequate because of the variation in underlying pathologic vascular changes. METHODS: This article presents a 32-year old patient with a 5 cm long segment of obstruction of the retrohepatic inferior vena cava involving the main hepatic veins with severe portal hypertension. RESULTS: After five unsuccessful attempts at percutaneous transluminal angioplasty, simultaneous hepatic venoplasty was conducted with the saphenous vein patch and retrohepatic inferior venacavoplasty by the expanded polytetrafluoroethylene patch with a 3 cm long cuff interposition for suprahepatic reconstruction of the inferior vena cava. Hypothermic preserved liver perfusion after vascular isolation and femoroportoaxillary venovenous bypass with a centrifugal blood pump throughout the anhepatic stage ensured safe operation on the liver and maintained hemodynamics. Early postoperative anticoagulant is recommended. CONCLUSIONS: An uneventful postoperative course and a 10-month follow-up showing excellent condition indicated this one-stage simultaneous patch hepatic venoplasty and cavoplasty to be adequate for appropriate correction very of complex obstructive vascular lesions in Budd Chiari syndrome. PMID- 8488479 TI - Symptomatic recurrent carotid stenosis and aneurysmal degeneration after endarterectomy. AB - BACKGROUND: Aneurysmal degeneration of a carotid reconstruction was not recognized until the patient, who was known to have recurrent carotid artery stenosis, had a thromboembolic stroke. This sequelae of carotid endarterectomy is a serious complication, associated with a high morbidity and mortality rate. This review was conducted to establish the risk of transient ischemic attack and stroke for patients found to have recurrent carotid stenosis associated with aneurysmal degeneration of the carotid artery after endarterectomy. METHODS: A case is reported, and 100 literature references of aneurysmal degeneration of the carotid artery after endarterectomy were reviewed. RESULTS: False aneurysm from anastomotic disruption was the most common presentation identified in the cases reviewed. Nineteen of the patients had a significant neurologic event; however, three (50%) of six patients with aneurysm and recurrent carotid artery stenosis had a transient ischemic attack or stroke. CONCLUSIONS: The incidence of neurologic symptoms is markedly increased when recurrent carotid artery stenosis is associated with carotid aneurysm. During postoperative surveillance after endarterectomy, the identification of recurrent carotid artery stenosis requires evaluation for aneurysmal degeneration of the carotid artery with duplex scanning. These patients are at significant risk for transient ischemic attack and stroke. This rare complication merits operative repair. PMID- 8488480 TI - Hyperparathyroid crisis and posterior mediastinal parathyroid adenoma: a case for preoperative localization. AB - Hyperparathyroid crisis is a rare, life-threatening condition that requires prompt removal of the involved parathyroid gland(s). This report describes a patient with hyperparathyroid crisis caused by a mediastinal parathyroid adenoma, which was localized before operation and removed at the initial operation, without neck exploration. Surgical approaches to hyperparathyroid crisis and the importance of preoperative localization studies are discussed. PMID- 8488481 TI - Primary appendiceal malignancy. PMID- 8488482 TI - Use of biphosphonates in preoperative treatment of patients with hyperparathyroidism. PMID- 8488483 TI - Prognostic factors of carcinoid tumor of the appendix smaller than two centimeters. PMID- 8488484 TI - Genetic markers in thyroid tumors. PMID- 8488485 TI - Feeding jejunostomy techniques. PMID- 8488486 TI - The Teratology 33rd annual meeting June 28-July 1, 1993 and the Neurobehavioral Teratology Society 17th annual meeting June 26-29, 1993. Tucson, Arizona. Abstracts. PMID- 8488487 TI - [Rapid detection of antimicrobial residues in slaughter animals via ATP determination]. AB - A rapid antibiotic test was developed, based on ATP/bioluminescence, to detect antimicrobial residues in slaughter animals as early as possible. Several aspects that influence the assay were studied. For many samples of renal fluid the results of the test agreed very well with the inhibition zones obtained with the new Dutch agar diffusion test. The ATP/antibiotic test offers the possibility of detecting a wide range of antibiotics in renal fluid within 3.5 to 4 hours after receipt of the kidney samples. The detection level is comparable to that of existing agar diffusion tests. PMID- 8488488 TI - [Consequences of a Salmonella typhimurium infection on a veal calf farm]. AB - An outbreak of Salmonella typhimurium in veal calves is described. The pattern of resistance to antibiotics was unique in the Netherlands at the time of the outbreak. Other factors besides antibiotic resistance also played a role in the outbreak, resulting in a mortality exceeding 90%. PMID- 8488489 TI - [Toxocara species, unwelcome guests]. PMID- 8488490 TI - [The annual incidence of salmonellosis in humans in The Netherlands]. PMID- 8488491 TI - [Registration of veterinary drugs: order or chaos?]. PMID- 8488492 TI - [Castration of male cats]. PMID- 8488493 TI - [Food allergy in Westies]. PMID- 8488494 TI - [A heifer with very difficult calving]. PMID- 8488495 TI - [The clinical case. Warmblood foal, male, 3 days old]. PMID- 8488496 TI - [Horses as trichinosis carriers]. PMID- 8488497 TI - [Cauda equina syndrome in a Fleckvieh bull after a pathological fracture of the first sacral vertebra caused by a spindle cell sarcoma]. AB - A 9 month old Simmental fattening bull was presented with signs of a cauda equina syndrome. An epidurographic examination was made after thorough clinical, neurological and routine radiographic examination. The cause of the cauda equina compression--a spindle cell sarcoma--was revealed by the pathologic-histologic examination. This tumor caused the compression of the cauda equina and pathologic transverse fracture of the body of the first sacral vertebra and cranial epiphyseal fracture of the 1st and the 3rd sacral vertebra as well as the separation of the arcus from the first and second sacral vertebral bodies. Some other diseases which can cause cauda equina syndrome are mentioned. PMID- 8488498 TI - [The effect of antepartum doses of selenium-vitamin E combinations on the incidence of puerperal disorders in cattle]. AB - The effect of a single i.m. injection of 0, 5, 25 or 50 mg Se and 60, 300 or 600 mg vitamin E (12 combinations) about ten days before delivery on the incidence of post partum disturbances was investigated using 288 cows with selenium deficiency from six farms. The higher dose of Se, the lower was the frequency of fetal membrane retention (0 mg Se = 23.6%, 5 mg Se = 11.1%, 25 mg Se = 12.5%, 50 mg Se = 6.9%, p < 0.0001). This was independent of vitamin E. A beneficial effect of the higher Se doses together with vitamin E was noted in reduction in incidence of metritis, ovarian dysfunction and cysts. There was no significant difference in conception rate, services per conception or calving interval between the groups. PMID- 8488499 TI - [Eperythrozoonosis in sheep]. AB - In 1990/91 eperythrozoonosis in the sheep was seen in our clinic for the first time. In 10 animals out of 4 flocks infection with Eperythrozoon ovis was diagnosed. Most of the animals showed a transient parasitaemia with a temporary anaemia. A chronic high grade parasitaemia and anaemia were produced in one sheep by splenectomy. This animal showed haemoglobinuria following a haemolytic attack. In a lamb a high grade chronic parasitaemia occurred spontaneously. The parasitaemia lasted for over 7 months, and the lamb eventually died. PMID- 8488500 TI - [The content of hemoglobin in the blood and the abundant and trace elements in blood plasma and erythrocytes of sheep, fallow deer, dwarf goats and reindeer]. AB - Of the 4 species, the blood of fallow deer had the highest concentration of Hb (10.9 +/- 0.7) and that of pygmy goats (6.5 +/- 1.4 mmol/l) the lowest. The highest concentration of protein in the plasma was found in the reindeer (81.2 +/ 2.1) and the lowest in the pygmy goats (59.1 +/- 4.3 g/l). High values of ascorbic acid were recorded in the reindeer (16.4 +/- 2.4) and in the Finnish sheep (16.3 +/- 2.5 micrograms/ml). There existed some differences in the concentrations of Na, K, Ca, Mg, Pa, Fe, Cu and Zn in the plasma of the sheep of 7 different breeds under similar nutritional conditions. The erythrocytes of the sheep of 3 breeds and that of fallow deer, of pygmy goats and of reindeer uniformly had a low Na- and a high K-concentration. The Ca-concentration of the erythrocytes of the sheep of most breeds and that of the fallow deer and pygmy goats was very low, that of Mg and Zn was higher than in the plasma. PMID- 8488501 TI - [Spavin in horses--clinical, radiological and scintigraphic findings]. AB - Both hock joints were examined clinically, radiologically and scintigraphically in 80 horses with special regard to bone spavin. The positive x-ray and bone scan results corresponded in most cases. It was evident that there was no correlation between degree of lameness and/or extent of radiological findings and increased radioactive uptake in the joint. Scintigraphic evaluation may demonstrate early changes at the onset of bone spavin as well as the frequent bilateral nature of the condition. PMID- 8488502 TI - [Clinico-toxicologic aspects of non-steroidal anti-inflammatory agents in the dog and cat]. AB - The use of nonsteroidal anti-inflammatory drugs (NSAID) is increasing in small animal practice. This has resulted in a greater incidence of acute as well as chronic toxicosis. NSAID toxicoses are usually manifested by gastrointestinal upset, such as nausea, vomiting, gastrointestinal hemorrhage and ulceration. The mechanisms by which these drugs cause their toxic effects are mainly associated with the impaired prostaglandin synthesis and therefore the reduced physiological cytoprotection of the mucosa. In addition, local cellular damage due to the acid effects of NSAID contribute to the GI-toxicity. Treatment of acute intoxication involves maintenance of vital function as well as early decontamination of the gastrointestinal tract and symptomatic treatment (correction of bleeding tendency and local acidosis). Symptomatic care of gastrointestinal damage is the most important aspect of dealing with chronic intoxication. A reduction of acid production as well as a stimulation of the repair mechanism of the mucosa is the aim of the therapy. PMID- 8488503 TI - [The measurement of the sensory antidromic nerve conduction velocity in the dog]. AB - Sensory neurography is a diagnostic aid in the evaluation of peripheral nerve function. Up to now, the measurement of the orthodromic nerve conduction velocity has been supposed to be the only valuable method in veterinary medicine. However, there is always a certain risk because the procedure requires immobilized animals. In this article, the measurement of the sensory antidromic nerve conduction velocity in the superficial radial and the superficial peroneal nerve of the dog is described as an alternative method. Usually, this procedure can be done without immobilisation or general anesthesia. Thus, the antidromic nerve conduction velocity represents a valuable screening method for evaluation of peripheral nerve function. In dogs without changes in laboratory values and without signs of neurologic disease, the nerve conduction velocity is 52.5 +/- 6.6 m/s (mu +/- s) for the superficial radial nerve and 49.4 +/- 5.7 m/s (mu +/- s) for the superficial peroneal nerve. PMID- 8488504 TI - [BT-PABA/xylose test in the cat?]. AB - The BT-PABA/Xylose test was used in 10 healthy cats and 49 cats with chronic diarrhea. In seven cats the test was performed three times in order to investigate individual variability. There was a statistically significant difference between the control group and the patients in the mean peak concentration of xylose, but no difference between groups of different diseases. The mean peaks of PABA were not significantly different between the control group and the patient group. Due to high individual variation in healthy cats the BT PABA/Xylose test cannot be considered to be a useful test in feline diagnosis. PMID- 8488505 TI - [Anatomic fundamentals and species-specific movements of the elbow joint and proximal radioulnar joint of domestic cats]. AB - The elbow joint of the cat is more than a simple cylindrical joint and cannot be compared to that of the dog. The structure of the bone ends, arrangement of ligaments and the shapes of the joint surfaces, which are described individually, emphasize that the elbow joint, together with the proximal radioulnar joint, have an important role to play in feline-specific limb functions. PMID- 8488506 TI - [Pain prevention and pain treatment in small and large domestic animals]. AB - The aim of this article is to emphasize the need for analgesic medication in animals in possibly painful situations, especially in the postoperative period. The two large groups of compounds used as analgesics--the opiates and the nonsteroidal antiinflammatory drugs (NSAIDs)--are described with special reference to their pharmacokinetics, side-effects and toxicity, their mechanism of action, their indications and contraindications. Recommended doses of the different drugs available are given for the dog, the cat, the horse, the swine and the small and large ruminants. PMID- 8488507 TI - [The raising and worship of monkeys in the late period of ancient Egypt]. AB - New finds of pathologically altered skeletal remains of baboons originating from the galleries under the temple of the god Thot in Tuna el-Gebel/Middle Egypt enlarge the knowledge of diseases observed in these animals, which were kept in non-appropriate conditions during ancient Egyptian time. "Rickets" and chronic deformations of the joints ("arthrosis") were observed most frequently. Additional cases of bone tumors and osteomyelitis were noted. PMID- 8488508 TI - Financial analysis of medical staff development plans. PMID- 8488509 TI - Medical staff development: planning for a successful program. PMID- 8488510 TI - Developing a physician-hospital organization. PMID- 8488511 TI - Medical practice evaluation and analysis. PMID- 8488512 TI - Economic credentialing. PMID- 8488513 TI - The valuation of medical practices. PMID- 8488514 TI - Financial analysis of medical office buildings. PMID- 8488515 TI - Designing a physician ecosystem. PMID- 8488516 TI - Can carotid endarterectomy be improved by neurovascular monitoring? PMID- 8488517 TI - Cigarette smoking and alcohol consumption as risk factors for aneurysmal subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage is a serious disease despite recent improvements in medical and surgical treatment. Hence, identification of modifiable risk factors for subarachnoid hemorrhage is important. METHODS: We compared the smoking and drinking habits of 278 consecutive patients with aneurysmal subarachnoid hemorrhage, aged 15-60 years (145 men and 133 women) with those of 314 hospitalized control patients (164 men and 150 women) who did not differ in regard to age, day of onset of symptoms, and acuteness of disease onset. RESULTS: Multiple logistic regression analysis showed that recent alcohol intake and smoking, but not hypertension, were significant independent risk factors for hemorrhage. After adjustment for age, hypertension, and smoking status, men who had consumed 1-40, 41-120, or > 120 g of alcohol within the 24 hours preceding the onset of illness had a relative risk of hemorrhage of 0.3 (95% confidence interval [CI], 0.1-0.8), 2.5 (95% CI, 1.1-5.5), and 4.5 (95% CI, 1.5-12.9), respectively, compared with men who had consumed 0 g. Women who had consumed 1-40 or > 40 g of alcohol had a risk of hemorrhage of 0.4 (95% CI, 0.2-0.8) and 6.4 (95% CI, 2.3-17.9), respectively, compared with women without use of alcohol. Heavily smoking (> 20 cigarettes per day) men and currently smoking women had adjusted relative risks of hemorrhage of 7.3 (95% CI, 3.8-14.3) and 2.1 (95% CI, 1.2-3.6), respectively, compared with men who had never smoked and with women who were not current smokers. Higher levels of erythrocyte mean corpuscular volume in patients with subarachnoid hemorrhage than in control subjects supported the notion of different smoking and drinking habits. CONCLUSIONS: Recent heavy alcohol intake and current smoking seem to be independent risk factors for aneurysmal subarachnoid hemorrhage. PMID- 8488518 TI - Silent brain infarctions in patients with first-ever stroke. A community-based study in Umbria, Italy. AB - BACKGROUND AND PURPOSE: The relative frequency of computed tomographic evidence of old cerebral infarctions without prior history of stroke, and their effect on short- and long-term outcome of patients with first-ever ischemic stroke, are currently unknown. Silent infarctions may relate to specific risk factors and may influence the rate of survival free of handicap. METHODS: We studied the prevalence of such lesions in patients registered with SEPIVAC, a community-based survey of stroke incidence and outcome in the Sixth Local Health Unit of Umbria, Italy. Of 375 first-ever strokes, 209 patients with cerebral infarction (computed tomogram done within 30 days after the stroke) were included in this study. Computed tomograms were reviewed blindly, and cases were classified as having a single lesion or multiple lesions; in the latter case, it was assumed that at least one silent brain infarction was present. The two groups were compared in terms of risk factors and outcome. To avoid a selection bias, these patients were also compared with 68 patients who were not submitted to computed tomography but were judged on clinical grounds to have a > 90% probability of having suffered a cerebral infarction. RESULTS: Risk factors and outcome did not differ between patients without and with a computed tomogram. In the latter group, 80 patients (38.3%; 95% confidence interval, 31.7%-44.9%) had silent brain infarction. Male sex (odds ratio, 1.84; 95% confidence interval, 1-3.4), ischemic changes on an electrocardiogram (odds ratio, 2.5; 95% confidence interval, 1.3-4.9), and--in the multivariate analysis--hypertension (odds ratio, 1.46; 95% confidence interval, 1.1-2) were significantly more frequent in these patients. Outcome at 1, 6, and 12 months was not influenced by the presence of silent infarctions. CONCLUSIONS: This community-based study shows that silent brain infarctions in patients with first-ever stroke are not significantly related to risk factors commonly described in hospital-based series (atrial fibrillation, transient ischemic attack, etc.); rather, silent infarctions seem to be a marker of widespread vascular disease. PMID- 8488519 TI - Two clinically distinct lacunar infarct entities? A hypothesis. AB - BACKGROUND AND PURPOSE: We investigated the hypothesis that patients with one or more asymptomatic lacunar infarcts and those with only one symptomatic lacunar infarct represent two clinically distinct lacunar infarct entities. METHODS: In a prospective series of 100 lacunar infarct patients, univariate and multivariate logistic regression analysis was performed on clinical features, vascular risk factors, and leukoaraiosis between patients with and without asymptomatic lacunar infarcts. RESULTS: Patients with asymptomatic lacunar infarcts had hypertension significantly more often (71% versus 43%; [crude] odds ratio, 3.31; 95% confidence intervals, 1.16-9.43; p < 0.05) and had leukoaraiosis significantly more often (71% versus 19%; [crude] odds ratio, 10.67; 95% confidence intervals, 3.81-32.10; p < 0.001) than those with only a symptomatic lacunar infarct. After multivariate logistic regression analysis, only leukoaraiosis was significantly associated with the presence of asymptomatic lacunar infarcts. The asymptomatic lacunar infarcts differed in location, involved vascular territory, and volume from the symptomatic infarcts. CONCLUSIONS: Two distinct lacunar infarct entities might be broadly distinguished during life: lacunar infarct patients with a single, symptomatic lacunar infarct, and patients with multiple lacunar infarcts and a high frequency of hypertension and leukoaraiosis, in which the underlying small-vessel vasculopathy might be different. PMID- 8488520 TI - Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case-control study. AB - BACKGROUND AND PURPOSE: Apolipoprotein E polymorphism may influence the early development of coronary artery disease. We investigated the putative role of apolipoprotein E phenotypes in cerebral infarction. METHODS: The apolipoprotein E phenotypes of 69 patients (mean +/- SD age, 72 +/- 11 years) who had suffered completed stroke or a transient ischemic attack and 68 sex- and age-matched control subjects free of cerebrovascular disease were determined by isoelectric focusing. The relative frequency of the apolipoprotein E phenotypes in the general population was estimated in 498 healthy blood donors (mean age, 37 years). RESULTS: The prevalences of hypertension, diabetes mellitus, obesity, and intermittent claudication were significantly higher in patients than in control subjects. Serum lipid and apolipoprotein B concentrations and the composition of very low density lipoproteins were not significantly different between patients and control subjects. Apolipoprotein A-I and E levels were significantly lower in patients. Cholesterol levels were higher in male patients than in male control subjects (5.10 +/- 1.46 versus 4.41 +/- 0.80 mmol/L; p = 0.036), and the ratio of apolipoprotein A-I to B was lower (0.77 +/- 0.29 versus 1.03 +/- 0.37; p < 0.001). The E3/E3 phenotype was more frequent in control subjects (85%) than in patients (72.5%; p < 0.05) and healthy blood donors (64%; p < 0.02). The E3/E2 phenotype was more frequent in patients (10.1%) than in control subjects (1.4%; p < 0.05). A stepwise logistic regression showed that the presence of stroke was significantly related to high blood pressure (p < 0.0001), low apo E levels (p < 0.008), obesity (p < 0.041), the apo E phenotype (p < 0.05), and diabetes mellitus (p < 0.05). CONCLUSIONS: The E3/E3 phenotype may protect against early vascular morbidity, and the epsilon 2 gene may be a risk factor for cerebrovascular morbidity, possibly related to diabetes, hypertension, and/or obesity. PMID- 8488521 TI - Reactivity of cerebral blood flow to carbon dioxide in various types of ischemic cerebrovascular disease: evaluation by the transcranial Doppler method. AB - BACKGROUND AND PURPOSE: The response of cerebral blood flow to changes in the arterial carbon dioxide partial pressure (i.e., carbon dioxide reactivity) has been evaluated as a parameter of cerebral perfusion reserve in patients with cerebrovascular disease. In this study, variations in this reactivity in various ischemic cerebrovascular diseases were evaluated by a newly established method, a transcranial Doppler technique. METHODS: Thirty-three patients with symptomatic cerebrovascular disease, 13 patients with asymptomatic cerebral infarction, and 25 age-matched normal control subjects were investigated. The symptomatic patients were divided into three groups; those with unilateral carotid artery obstruction, those with cortical infarction, and those with lacunar infarction. The carbon dioxide reactivity of each subject was determined by simultaneously measuring the mean spatial Doppler frequency in the middle cerebral artery and the end-tidal carbon dioxide partial pressure under normocapnic, hypercapnic, and hypocapnic conditions. RESULTS: In the patients with carotid obstruction, the carbon dioxide reactivity of the hemisphere ipsilateral to the obstruction was more impaired than the reactivity of the symptomatic hemispheres in any other group, and was significantly less than in the contralateral asymptomatic hemisphere (p < 0.01). In patients with cortical infarction, the carbon dioxide reactivity of the symptomatic hemisphere was significantly less than in normal control subjects (p < 0.05) and was also less than that of the contralateral asymptomatic hemisphere (p < 0.05). In patients with lacunar infarction, the carbon dioxide reactivity of both hemispheres was significantly less than that in normal controls (p < 0.01), although there was no difference between the symptomatic and asymptomatic hemispheres. In patients with asymptomatic infarction, the carbon dioxide reactivity was also less than that in normal controls (p < 0.01). CONCLUSIONS: The carbon dioxide reactivity of cerebral blood flow measured by this transcranial Doppler technique may be useful for characterizing the hemodynamic changes that occur in various types of ischemic cerebrovascular disease. PMID- 8488522 TI - Contrast-enhanced transcranial color-coded real-time sonography. Results of a phase-two study. AB - BACKGROUND AND PURPOSE: Transcranial color-coded real-time sonography has been developed as a promising new bedside procedure to monitor central nervous system parenchymal and vascular pathology; the present study was designed to investigate the potential role of galactose microparticles (SH U 508 A) as a new ultrasound contrast-enhancing agent for transcranial sonography. METHODS: Ten patients (four women and six men, 24-63 years of age) with a broad spectrum of central nervous system pathology were investigated by transcranial color-coded real-time sonography in a phase-two clinical study. After conventional ultrasound examination, all patients received a maximum of six injections of 10 ml with 200, 300, or 400 mg/mL SH U 508 A. The intracranial vessels were scanned by color flow imaging in the axial and coronal planes through a transtemporal acoustic bone window; in addition, the vertebrobasilar system was followed through the foramen magnum. RESULTS: SH U 508 A was well tolerated without side effects. In axial and coronal scans, the application of SH U 508 A resulted in detection of peripheral branches of the anterior, middle, and posterior cerebral arteries, as well as the posterior communicating and superior cerebellar arteries. In addition, the deep cerebral veins (i.e., inferior sagittal sinus, internal cerebral veins, great cerebral vein of Galen, straight sinus, and the confluence sinuum) were revealed. The transforaminal approach led to detection of the main infratentorial branches (anterior inferior, posterior inferior, and superior cerebellar arteries). One patient could not be insonated without contrast, but after SH U 508 A the trunks of the large intracranial arteries were detected. No obvious changes in the ultrasound pattern of the central nervous system parenchyma were observed. CONCLUSIONS: These preliminary data indicate that the use of a transpulmonary ultrasound contrast agent (SH U 508 A) may substantially broaden the spectrum and potential diagnostic utility of transcranial ultrasound by allowing detection of supratentorial peripheral central nervous system arteries, deep cerebral veins, and (through the foramen magnum) the entire vertebrobasilar system, including the cerebellar arteries. PMID- 8488523 TI - Sneddon's syndrome: diagnosis by skin biopsy and MRI in 17 patients. AB - BACKGROUND AND PURPOSE: Sneddon's syndrome, characterized by generalized livedo racemosa and cerebrovascular lesions, is an underdiagnosed disease. We evaluated clinical, laboratory, histological, and neuroradiological findings in a series of 17 patients to improve diagnostic criteria for Sneddon's syndrome. METHODS: Patients with generalized livedo racemosa and cerebrovascular events were included in the study. All underwent neurological and dermatological examination, skin biopsy, computed tomographic scan, magnetic resonance imaging as well as magnetic resonance angiography, sonography of the extracranial arteries, and a comprehensive laboratory protocol. RESULTS: Completed stroke was present in eight patients, and 15 reported transient neurological deficits. Magnetic resonance imaging yielded cerebral abnormalities in 16 of 17, whereas computed tomographic scans were abnormal in only 12 of 16 patients. Magnetic resonance imaging revealed more lesions in individual patients than did computed tomography. Magnetic resonance angiography demonstrated patent intracranial vessels in 16 of 17 patients. Skin biopsy showed distinct histopathological findings in all patients. The involved vessels were small to medium-sized arteries at the border between dermis and subcutis. Early inflammatory reactions were followed by subendothelial proliferation and a late fibrotic stage. Laboratory examinations showed impaired creatinine clearance in eight patients, whereas all other laboratory tests, including antiphospholipid antibodies, were normal. CONCLUSIONS: In this series, magnetic resonance imaging and skin biopsy were useful for confirmation of the diagnosis of Sneddon's syndrome. Magnetic resonance findings were not specific, but the high sensitivity for detection of asymptomatic brain lesions helped to confirm the diagnosis in patients with transient symptoms. Histological features of skin biopsies were characteristic if appropriate techniques were employed. PMID- 8488524 TI - Cardiovascular changes during focal cerebral ischemia in rats. AB - BACKGROUND AND PURPOSE: Recent studies have suggested that cerebral infarction influences autonomic activity and may contribute to sudden death. The goal of this study was to examine effects of focal cerebral infarction on mean arterial pressure and heart rate. METHODS: Halothane-anesthetized rats were assigned to two groups: stroke (n = 10), in which the middle cerebral artery or an adjacent vessel was embolized with a silicone cylinder, and sham (n = 8), in which rats were sham embolized (saline). Arterial pressure and heart rate were measured for 90 minutes and again 24 hours after vascular occlusion. A change in electroencephalographic amplitude of -45% after embolization was used to determine if a significant degree of infarction was present. RESULTS: Vascular occlusion produced a significant increase in mean arterial pressure at 10, 60, and 90 minutes (p < 0.05). Changes in heart rate were significantly greater (p < 0.05) than in sham-treated rats at 10 and 30 minutes after embolization. In contrast, mean arterial pressure and heart rate measured 24 hours after embolization were similar in both groups. Anatomic analysis of the infarcted areas demonstrated that either insular cortex or amygdala was affected in all embolized rats. CONCLUSIONS: This study indicates that cerebral infarction produces a transient elevation of mean arterial pressure and heart rate. However, within 24 hours both parameters returned to preinfarcted levels. Our findings are consistent with clinical reports that indicate that mean arterial pressure and heart rate of stroke patients are similar to those of other groups when they are admitted to the hospital, although other cardiovascular parameters are greatly altered. PMID- 8488525 TI - Intracellular pH during reperfusion influences evoked potential recovery after complete cerebral ischemia. AB - BACKGROUND AND PURPOSE: Increasing ischemic duration delays recovery of intracellular pH and depresses recovery of somatosensory evoked potentials. We tested whether manipulation of the rate of pH recovery influences evoked potential recovery after complete ischemia. METHODS: Four groups of eight anesthetized dogs underwent 12 minutes of complete ischemia followed by 4 hours of reperfusion with either 1) normocapnia, 2) normocapnia and acetazolamide (25 mg/kg at reperfusion plus 12.5 mg/kg per hour, 3) hypocapnia, or 4) hypercapnia. Intracellular pH was measured by phosphorus magnetic resonance spectroscopy, and intracellular bicarbonate was calculated using sagittal sinus partial pressure of CO2 during reperfusion. RESULTS: In the normocapnic control group, intracellular pH decreased from 7.10 +/- 0.04 (+/- SEM) to 6.13 +/- 0.08 during ischemia and recovered to 6.90 +/- 0.08 by 30 minutes of reperfusion. Bicarbonate also largely recovered (9.9 +/- 1.6 mM). With acetazolamide pH (6.51 +/- 0.10) and estimated bicarbonate (4.8 +/- 1.3 mM) remained depressed at 30 minutes and did not fully recover until 60-75 minutes. However, percent recovery of somatosensory evoked potential amplitude at 4 hours of reperfusion was less with acetazolamide (23 +/- 4%) than in the control group (52 +/- 5%). With hypercapnic reperfusion, which delayed pH recovery but not bicarbonate recovery, evoked potential recovery was also depressed (27 +/- 5%). With hypocapnic reperfusion, which delayed bicarbonate recovery but not pH recovery, evoked potential recovery (52 +/- 6%) was not depressed compared with controls. Recovery of adenosine triphosphate and oxygen consumption was similar among groups. CONCLUSIONS: Delayed recovery of intracellular pH with or without delayed recovery of bicarbonate during reperfusion further impairs somatosensory evoked potential recovery independent of recovery of high-energy phosphates. Persistence of acidosis during reperfusion can contribute to postischemic electrophysiological deficit. PMID- 8488526 TI - Risk area and infarct area relations in the hypertensive stroke-prone rat. AB - BACKGROUND AND PURPOSE: Our purpose was to characterize the surface area of the infarct and the surface area at risk of infarction as defined spatially by arterial anastomoses to determine whether position, size, or shape of the infarct and the area at risk were related in stroke-prone rats or hybrid rats. METHODS: Stroke-prone rats (n = 18; mean +/- SEM blood pressure, 182 +/- 8 mm Hg) and hybrid rats (n = 18; mean +/- SEM blood pressure, 147 +/- 6 mm Hg; p < 0.05) were anesthetized and the left middle cerebral artery was occluded with a ligature. The rats were killed 7 days later, arterial anastomoses were made visible with latex, the brains were fixed in formalin, and film recorded the infarct and anastomoses. Anastomoses and infarcts were digitized for measurements of risk area, luminal width, and infarct area. RESULTS: Mean risk area was similar in size, length, width, and variability in stroke-prone rats (area, 85 +/- 5 mm2) and hybrid rats (area, 84 +/- 7 mm2; p > 0.05), whereas mean infarct area was larger, longer, wider, and less variable in stroke-prone rats (area, 53 +/- 6 mm2) than in hybrid rats (area, 15 +/- 11 mm2; p < 0.05). Infarct length was appreciably greater than infarct width in both groups, indicating that infarct shape was not amorphous. Spatial overlap maps indicated that the infarct area common to all stroke-prone rats was positioned centrally in the risk area and was surrounded by a variable infarct area, which indicated that the likelihood of infarction increased with distance from the anastomoses. Shape factors for both risk area and infarct area were significantly different within each rat group, which indicated that infarct shape did not uniformly parallel the anastomotic sites that determined risk area shape (p < 0.05). Risk area anastomoses and border zone width were linearly correlated in size and both were significantly wider in hybrid rats than in stroke-prone rats (p < 0.05), which suggests that the narrower border zone tissue was perfused by narrower anastomoses. CONCLUSIONS: We conclude that the position of the infarct within the risk area relates to luminal widths of conterminous anastomoses that define the risk area, but not to the size or shape of the area at risk of infarction defined spatially by the anastomoses. PMID- 8488527 TI - Protective efficacy of a hypothermic pharmacological agent in gerbil forebrain ischemia. AB - BACKGROUND AND PURPOSE: The novel muscarinic cholinergic partial agonist U-80816E was tested in the gerbil brief bilateral carotid occlusion ischemia model based on the rationale that the compound's hypothermic properties might afford effective protection of the selectively vulnerable hippocampal CA1 region. METHODS: Male gerbils were subjected to either 10 or 15 minutes of bilateral carotid occlusion, followed by histopathological assessment of the CA1 neuronal survival 7 days later. RESULTS: In saline-treated animals, 10 minutes of bilateral carotid occlusion resulted in a 30.5% loss of CA1 neurons, whereas a 15 minute insult resulted in a 49.6% loss. Administration of U-80816E (6 mg/kg i.p. 30 minutes before bilateral carotid occlusion and again 2 hours after reperfusion) resulted in a significant protective effect of the CA1 neuronal population with either duration of ischemia; neuronal loss was reduced to 12.6% in the milder model (p < 0.05 versus saline-treated) and 24.9% in the more severe model (p < 0.04 versus saline). However, the 6 mg/kg i.p. dose of U-80816E was found to produce a 1.0 degree C decrease in brain temperature (measured with a tympanic temperature probe) at 10 minutes of ischemia compared with that of saline-treated gerbils. At 10 minutes of reperfusion, after the 10-minute episode of ischemia, the brain temperature of the U-80816E-treated gerbils was 2.2 degrees C lower than that of saline-treated animals. When the U-80816E-treated gerbils were subjected to either 10 or 15 minutes of ischemia but placed in a heated chamber that prevented the hypothermic effects, no cerebroprotection was observed. CONCLUSIONS: These results show that the anti-ischemic efficacy of U 80816E is mediated through its hypothermic properties, thus suggesting the feasibility of pharmacologically induced hypothermia as a cerebroprotective approach. PMID- 8488528 TI - The antioxidant LY231617 reduces global ischemic neuronal injury in rats. AB - BACKGROUND AND PURPOSE: In the rat four-vessel occlusion model with 30 minutes of ischemia most agents have failed to be of benefit when given after ischemia. Because postischemia administration is more clinically relevant, we evaluated the antioxidant LY231617 (2,6-bis(1,1-dimethylethyl)-4-[[(1-ethyl)amino]methyl]phenol hydrochloride]) when administered after 30 minutes of four-vessel occlusion. METHODS: Male Wistar rats were subjected to 30 minutes of four-vessel occlusion. LY231617 was either given orally 30 minutes before ischemia or intravenously beginning at 30 minutes after the onset of ischemia. Hippocampal CA1 layer and striatal damage were rated on a scale of 0-3 (0, no damage; 3, > 90% cell loss). We also evaluated the ability of LY231617 to prevent iron-dependent lipid peroxidation and to prevent hydrogen peroxide-induced neuronal death of hippocampal neurons in primary culture by exposing cultures to a 50-microM concentration of hydrogen peroxide for 15 minutes in the presence of LY231617. RESULTS: Oral administration of LY231617 reduced both striatal and hippocampal CA1 damage by > 75% (p < 0.0001). In two separate experiments in which LY231617 was given intravenously beginning 30 minutes after occlusion, hippocampal and striatal damage were reduced by approximately 50% (p < 0.03) in the first experiment and by approximately 41% (p < 0.02) in the second experiment. Addition of 5 microM of LY231617 to primary hippocampal neuronal cultures antagonized the lethal effect of hydrogen peroxide (p < 0.05). Iron-dependent lipid peroxidation was also inhibited in a dose-related fashion. CONCLUSIONS: The significant reduction of ischemia-induced or hydrogen peroxide-induced neuronal damage and inhibition of lipid peroxidation by LY231617 observed in this study suggest that reactive oxygen intermediates play an important role in the events leading to neuronal death after global ischemia/reperfusion. PMID- 8488529 TI - Effect of the 21-aminosteroid tirilazad on cerebral pH and somatosensory evoked potentials after incomplete ischemia. AB - BACKGROUND AND PURPOSE: Postischemic evoked potential recovery correlates with acidosis during ischemia and early reperfusion. Acidosis promotes lipid peroxidation in vitro. We tested the hypothesis that the 21-aminosteroid tirilazad mesylate (U74006F), an inhibitor of lipid peroxidation in vitro, ameliorates somatosensory evoked potential recovery and acidosis during reperfusion after severe incomplete cerebral ischemia. METHODS: Cerebral perfusion pressure was reduced to 11 +/- 1 mm Hg (+/- SEM) for 30 minutes by cerebral ventricular fluid infusion in anesthetized dogs. Cerebral intracellular pH and high-energy phosphates were measured by magnetic resonance spectroscopy. Dogs were randomized to receive vehicle (citrate buffer; n = 8) or tirilazad (1 mg/kg; n = 8) before ischemia in a blinded study. RESULTS: Cerebral blood flow was reduced to 6 +/- 1 mL/min per 100 g during ischemia, resulting in nearly complete loss of high-energy phosphates and an intracellular pH of 6.0-6.1 in both groups. Initial postischemic hyperemia was similar between groups but lasted longer in the vehicle group. Tirilazad accelerated mean recovery time of intracellular pH from 31 +/- 5 to 15 +/- 3 minutes and of inorganic phosphate from 13 +/- 2 to 6 +/- 1 minutes. Recovery of somatosensory evoked potential amplitude was greater with tirilazad (49 +/- 3%) than vehicle (33 +/- 6%). Fractional cortical water content was less with tirilazad (0.819 +/- 0.003) than vehicle (0.831 +/- 0.002). CONCLUSIONS: Tirilazad attenuates cerebral edema and improves somatosensory evoked potential recovery after incomplete ischemia associated with severe acidosis. Accelerated pH and inorganic phosphate recovery indicates that this antioxidant acts during the early minutes of reperfusion. PMID- 8488530 TI - Acute ischemic stroke from fibrocartilaginous embolism to the middle cerebral artery. AB - BACKGROUND AND PURPOSE: Fibrocartilaginous embolism from the nucleus pulposus has been reported as a rare cause of spinal cord ischemia. We were unable to find previous reports of embolism from this source to cerebral arteries. CASE DESCRIPTION: A previously healthy 17-year-old girl fell during a basketball game. Left hemiparesis and unresponsiveness developed followed by signs of right uncal herniation and death over a 3-day period. There was no evidence of neck, head, or spine trauma, and cardiac evaluation was normal. Neuropathological examination showed extensive ischemic infarction of the right middle cerebral artery territory, brain edema, and herniation. Complete embolic occlusion of the right middle cerebral artery by fibrocartilaginous material, consistent with nucleus pulposus, was documented. Small, terminal coronary artery branches also showed embolism by the same material and limited areas of myocardial infarction. CONCLUSIONS: Acute cerebral embolism after minor trauma in a young patient may be rarely due to fibrocartilaginous embolism from the nucleus pulposus. The pathogenesis of this problem remains poorly understood, but systemic embolism appeared to have occurred in this case. PMID- 8488531 TI - Computed tomographic evidence of an extensive thrombosis and infarction of the deep venous system. AB - BACKGROUND: Massive bilateral infarcts due to deep venous system thrombosis are extremely rare and poorly documented. We present a case with computed tomographic evidence of both thrombosis and infarction of the whole deep venous system. CASE DESCRIPTION: A previously healthy 30-year-old woman who had taken oral contraceptives for 3 years complained of recurrent headaches and transient visual obscuration. Three months later, she suddenly became comatose and was found to have papilledema. She rapidly worsened, became decerebrate, and died within 48 hours. Noncontrast computed tomographic scan showed the spontaneous hyperdensity of the thrombosed deep veins and a massive bilateral centrobasilar hypodensity suggestive of a deep venous system infarction. CONCLUSIONS: This case shows that cerebral venous thrombosis can masquerade during 3 months as benign intracranial hypertension and then make a dramatic extension to the deep cerebral veins. It illustrates extensive thrombosis of the deep venous system as a possible cause of rapid coma and decerebration and stresses the importance of computed tomographic scan to show both the thrombosed veins and the venous infarct, which allows delineation of the deep venous system territory. PMID- 8488532 TI - Suppression of protein synthesis in the reperfused brain. AB - BACKGROUND: Brain ischemia and reperfusion produce profound protein synthesis alterations, the extent and persistence of which are dependent on the nature of the ischemia, the brain region, the cell layer within a region, and the particular proteins studied. After transient ischemia, most brain regions recover their protein synthesis capability; however, recovery in the selectively vulnerable areas is poor. It is unknown whether this phenomenon itself provokes or is a consequence of the process of neuronal death. SUMMARY OF REVIEW: Protein synthesis suppression during ischemia is due to energy depletion, but this is quickly reversed upon recirculation. Reperfusion does not appear to damage DNA or transcription mechanisms, although there are changes in the profile of transcripts being made. Similarly, purified ribosomes isolated from reperfused brains can make the normal repertoire of proteins and heat-shock proteins. However, during early reperfusion, newly synthesized messenger RNAs appear to accumulate in the nucleus; this alteration in RNA handling could reflect disruption at any of several steps, including posttranscriptional processing, nuclear pore transport, cytoskeletal binding, or formation of the translation initiation complex. Another mechanism that may be responsible for protein synthesis suppression during late reperfusion is progressive membrane destruction, with consequent shifts in the concentration of ions crucial for ribosomal function. CONCLUSIONS: Protein synthesis suppression after ischemia likely involves a progression of multiple mechanisms during reperfusion. Although the recent work reviewed here offers new insight into the potential mechanisms disrupting protein synthesis, detailed understanding will require further investigation. PMID- 8488533 TI - Denial of illness in stroke. AB - BACKGROUND: The effects of stroke on classically nondominant hemisphere functions have received less attention than those on the dominant hemisphere, but visuospatial neglect and denial of illness both produce significant morbidity. SUMMARY OF COMMENT: The early literature on denial of illness is discussed and the etiological theories are examined. These are explanations based on deficits of higher mental function, impaired sensory input (especially proprioceptive), an abnormal representation of body image, psychodynamic defense mechanisms, and/or premorbid personality factors. CONCLUSIONS: Denial of illness is an important consequence of stroke. No explanation thus far proposed is entirely satisfactory. The consequences on rehabilitation and strategies for therapy have not been adequately investigated. PMID- 8488534 TI - Is aspirin effective in preventing strokes in diabetic patients? PMID- 8488535 TI - Blood viscosity and cerebral blood flow. PMID- 8488536 TI - Capsular warning syndrome preceding pontine infarction. PMID- 8488537 TI - Significance of antibody to hepatitis B core antigen in blood donors as determined by their serologic response to hepatitis B vaccine. AB - Because large numbers of volunteer blood donors may be disqualified for "false positive" results on tests for antibody to hepatitis B core antigen (anti-HBc), a more specific definition of anti-HBc enzyme immunoassay (EIA)-reactive was evaluated, including only those donor samples that were "strongly" reactive (sample-to-cutoff absorbance ratio, < 0.45). Results using this definition and other anti-HBc test methods were compared to the serologic response (antibody to hepatitis B surface antigen [anti-HBsAg]) to hepatitis B vaccination. Fifty-eight volunteer blood donors who had previously been deferred as donors, because of reactive anti-HBc tests (all other blood screening tests were negative, including those for HBsAg and anti-HBsAg) on two occasions, were vaccinated for hepatitis B. It was assumed that an anamnestic response to vaccine indicated past infection with hepatitis B, while a primary response to vaccine indicated lack of past infection. One (2%) of 43 donors with a historically "weak" anti-HBc (reactive absorbance ratio, > or = 0.45) had an anamnestic response to vaccine, compared to 8 (53%) of 15 with historically "strong" anti-HBc (reactive absorbance ratio, < 0.45) (p < 0.005). Anti-HBc testing using the microparticle EIA method also correlated well with hepatitis B vaccination results. The use of a narrower definition of "reactive" for anti-HBc EIA testing yielded much more specific, but slightly less sensitive, results. PMID- 8488538 TI - Blood donation leads to a decrease in natural killer cell activity: a study in normal blood donors and cancer patients. AB - Transfusion-induced immunosuppression has long been known to be beneficial for organ transplantation patients, but recent retrospective studies suggest that blood transfusions may be detrimental for patients with cancer. If autologous blood is used to avoid immunosuppression, the assumption is that the procedure, involving blood donation, is immunologically neutral. In the present study, this assumption was evaluated by monitoring 33 normal blood donors and 16 colorectal cancer patients before and after donation of 1 (500 mL) and 2 units of blood, respectively. The cancer patients belonged to the autologous arm of a randomized trial in which the effects of allogeneic versus autologous blood on cancer prognosis were studied. The patients donated 2 units of blood with an interval of 3 to 4 days between donations. Flow cytometric analysis revealed that blood donation by normal donors and cancer patients had no effect on the proportion of B, T, and natural killer (NK) cells. Only the total number of lymphocytes was significantly decreased in the normal donors on Day 12 after donation. Blood donation had no significant effect on T-cell function assessed by phytohemagglutinin stimulation in normal donors or in cancer patients donating 2 units of blood. A significant depression of NK cell function (88% and 74% of predonation levels) was observed in normal donors on Days 2 and 5 after donation; on Day 12, the activity was again normal. Colorectal cancer patients had a significantly depressed NK cell activity (54% of predonation activity) on Day 12 after the first donation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488539 TI - Storage of pools of six and eight platelet concentrates. AB - Platelet concentrates (PCs) prepared from units of whole blood are routinely stored singly at 20 to 24 degrees C and pooled prior to transfusion. Studies have been conducted to evaluate the in vitro properties of pools of six (n = 19) and eight (n = 17) ABO-identical PCs after storage, with comparative studies involving single units (n = 33). The pools were prepared using the sterile connecting device. One-day-old and 3-day-old PCs were pooled and stored for a total of 5 days in a container system consisting of two 1000-mL polyolefin containers. The pooled platelet suspension was divided approximately equally between the two containers. The platelet count was reduced by less than 5 percent during storage of the pools, which is similar to the reduction found with storage of control units of single PCs. The volume loss due to pooling was 9.6 +/- 1.9 percent (mean +/- 1 SD). The pH of the PC pools was approximately 7.0 after 5 days of storage, with no pool having a pH below 6.2. In vitro platelet properties, such as morphology score, extent of shape change induced by ADP, total ATP, aggregation response to ADP and collagen, response to hypotonic stress, lactate dehydrogenase discharge, and beta-thromboglobulin release, were similar for pools and control single PCs. In addition, comparable low levels of thymidine uptake were detected in the mononuclear leukocyte fraction of pooled and unpooled PCs that were stored for 5 days at 20 to 24 degrees C, which indicates that the mixing of lymphocytes in the pool did not stimulate in vitro immunologic reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488540 TI - Effective use of a strategy using assigned red cell units to limit donor exposure for neonatal patients. AB - Critically ill neonatal infants receive frequent small-volume red cell (RBC) transfusions for replacement of blood drawn for laboratory analysis or for treatment of symptomatic anemia secondary to underlying medical conditions and/or a relative bleeding diathesis. Retrospective review of transfusion practice in a hospital revealed that the donor exposure-to-transfusion ratio was 1:1.3. In an effort to limit donor exposure and decrease the risk of transfusion-transmitted disease, a sterile connection device was used for multiple small-aliquot preparations. Three neonatal infants were given part of the same RBC unit, and the assigned RBC unit was used only until it reached 14 days of age. These criteria resulted in 49-percent reduction in donor exposure for neonatal infants weighting less than 1500 g and 27-percent reduction for those weighing more than 1500 g. The donor exposure-to-transfusion ratio decreased to 1:2.5. RBC waste from syringe aliquot preparation and residual volume at Day 15 were a mean of 32 percent of the total unit volume. Of 722 transfusion occurrences, there were no reported adverse effects due to elevated potassium subsequent to transfusion of 14-day-old RBCs. This limited-donor-exposure strategy effectively meets the needs of a transfusion service and will reduce the donor exposures of neonatal infants in similar institutions. PMID- 8488541 TI - Characteristics of red cells irradiated and subsequently frozen for long-term storage. AB - Irradiation of blood components eliminates the risk of transfusion-associated graft-versus-host disease. Freezing directed or rare red cell units that are irradiated but not transfused would facilitate inventory management and would increase the transfusion options for the involved patients. However, no studies have been performed to evaluate whether prestorage irradiation damages subsequently frozen red cells. Ten normal volunteers donated a unit of whole blood on two separate occasions. One unit was irradiated with 15 Gy (1500 rad), stored at 4 degrees C for 6 days, and then frozen and stored at -75 degrees C for 56 days. The other unit (control) was similarly stored but was not irradiated. Aliquots of the units were tested on Day 0 and Day 6 and, after deglycerolization, on Day 62. Comparison of means and changes in means showed no significant differences in red cell ATP, 2,3 DPG, or supernatant hemoglobin and glucose in control and irradiated units. The difference in the change in supernatant potassium from Day 0 to Day 6 in control and irradiated units was significant (1.5 to 28.6 mmol/L vs. 1.5 to 48.5 mmol/L: p < 0.0001). Irradiation did not cause significant differences in postdeglycerolization red cell recovery (control, 84.5% vs. irradiated, 81.2%) or in 24-hour posttransfusion autologous red cell survival (control, 91.1% vs. irradiated, 90.9%). Red cells can be irradiated, stored at 4 degrees C for 6 days, and subsequently frozen with no increase in detectable damage as compared to controls that were not irradiated. PMID- 8488542 TI - Plateletpheresis: comparison of platelet yields, processing time, and white cell content with two apheresis systems. AB - Two apheresis systems (COBE Spectra and Fenwal CS-3000 Plus with TNX-6 chamber [CS-3000 Plus]) were compared by using their yield predictors and maximum processing times in regard to platelet yields and processing times (n = 200 each). Platelet yields (n = 50 each) and white cell (WBC) content (n = 20 each) from procedures using the current software revision (3.6) on the Spectra and various interface offset (IO) settings on the CS-3000 Plus were also compared. Significantly higher median platelet yields (4.88 [range, 1.84-9.97] vs. 4.57 [range, 2.82-9.20] x 10(11) platelets) and frequency of components with > or = 6.0 x 10(11) platelets (31.5 vs. 21.5%) were found with the Spectra. In the study with Spectra and the CS-3000 Plus IO settings, IO-10 and IO-13, overall, produced the most platelets, although the differences were not significant. All Spectra collections tested had < 5 x 10(8) WBCs, and, depending on the software revision, had either 85 percent (revision 3.6) or 100 percent (revision 2.5) of components with < 5 x 10(6) WBCs. To ensure that 100 percent of components contained < 5 x 10(8) WBCs when the CS-3000 Plus was used, IO settings of 10 or less were required, and to ensure components with < 5 x 10(6) WBCs, only IO-6 could be used. Spectra and CS-3000 Plus were capable of collecting large doses of platelets (up to the equivalent of 18 units) in processing times of 67 to 100 minutes with < 5 x 10(6) WBCs. PMID- 8488543 TI - Polyclonal antibodies against the NB1-bearing 58- to 64-kDa glycoprotein of human neutrophils do not identify an NB2-bearing molecule. AB - The neutrophil-specific NB antigen system has been serologically characterized with human alloantisera. Two alleles, NB1 and NB2, have been described; however, there may be important quantitative or qualitative variation in the expression of NB1 and NB2. Human alloantibodies have been used to identify the 58- to 64-kDa glycoprotein (GP) on which NB1 antigen is located, but an NB2 antigen-bearing molecule has not yet been identified. To identify the NB2 molecule, human alloantibody to NB1 was used to isolate the 58- to 64-kDa NB1 GP, and rabbits were immunized with this GP. Two rabbit antisera were produced. Both antisera immunoblotted and immunoprecipitated the 58- to 64-kDa GP on which NB1 is located, but neither identified the molecule on which NB2 is located. The inability of two rabbit polyclonal antibodies specific for the NB1 molecule to react with the NB2-bearing molecule suggests that considerable differences may exist between these two molecules or that NB2 as currently defined is not related to NB1. PMID- 8488544 TI - Lack of detection of human immunodeficiency virus type 1 DNA by polymerase chain reaction in the plasma and lymphocytes of seronegative exposed hemophiliacs. AB - Direct detection of human immunodeficiency virus type 1 (HIV-1) DNA in serum or plasma samples has been reported in seronegative as well as seropositive individuals. An alkaline lysis procedure was adapted for polymerase chain reaction (PCR) analysis of plasma specimens. Eighty-five seronegative hemophiliacs, 52 of whom had been exposed to HIV-contaminated blood components, and 19 seronegative at-risk individuals were studied. Each sample was extracted and amplified with SK38/39 gag primers at least three times. Seventy-six samples (72%) were consistently negative for HIV-1 DNA, 24 (22%) were positive only once, and 4 (3%) were positive twice. Genomic DNA from peripheral mononuclear cells was prepared from 12 of 76 negative samples, 18 of 24 samples that were positive once, and 2 of 4 samples that were positive twice and analyzed with both gag and long terminal repeat primers. None (0/32) of these cellular DNAs were positive for HIV-1, which suggests that these seronegative exposed hemophiliacs were not latently infected with HIV-1. In contrast, all (10/10) control cells from seropositive patients were positive with both primer pairs. The detection of HIV 1 DNA in serum or plasma may be prone to a high level of false-positive PCR signals and should be interpreted with caution. PMID- 8488545 TI - Large-volume hemocytometer chamber for accurate counting of white cells (WBCs) in WBC-reduced platelets: validation and application for quality control of WBC reduced platelets prepared by apheresis and filtration. AB - A detailed description is provided of a method using a large-volume (50 microL) hemocytometer to count very low numbers of white cells (WBCs) in platelet components. A method employing a Nageotte hemocytometer uses crystal violet stain and a standard microscope with a reading time of 5 to 10 minutes. The method is validated by using serial dilutions of known concentrations of WBCs in platelets and by correlation with a flow cytometric technique. The interobserver coefficient of variation was 11.9 percent for WBC concentrations > 2 per microL. Use of the method for the evaluation of 203 WBC-reduced platelet components prepared by apheresis or by filtration revealed that over 94 percent of components had WBC content < 5 x 10(6). This method could easily be applied in the routine quality control of WBC-reduced platelet components and in clinical studies employing these components. PMID- 8488546 TI - A rapid molecular diagnosis of posttransfusion graft-versus-host disease by polymerase chain reaction. AB - A woman with recurrent Paget's disease of the vulva developed acute graft-versus host disease (GVHD) 12 days after radical surgery and massive blood transfusion. Molecular diagnosis of lymphocyte chimerism in the peripheral blood was made by polymerase chain reaction (PCR) directed against a Y chromosome-specific sex determining region Y (SRY) gene. PCR with skin biopsy after onset of GVHD also revealed infiltration of SRY-positive donor lymphocytes. The diagnosis was confirmed by HLA-DNA typing with PCR-sequence-specific oligonucleotide that revealed the presence of complex HLA-DR chimerism in the peripheral lymphocytes collected after onset of GVHD. The use of SRY-directed PCR is a rapid technique for the early diagnosis of acute posttransfusion GVHD in female patients. PMID- 8488547 TI - Pure red cell aplasia following ABO-incompatible bone marrow transplantation: response to erythropoietin. AB - Allogeneic bone marrow transplants with major ABO incompatibility may be associated with delayed erythroid engraftment. A case of a male patient with erythroleukemia (blood group O) who received a bone marrow transplant from an HLA identical sibling (blood group AB) is reported. The bone marrow transplantation was followed by normal myeloid and megakaryocytic engraftment, but pure red cell aplasia was present for more than 230 days after bone marrow transplant. Despite documentation of an elevated endogenous erythropoietin level (360 mU/mL; normal value, < 19 mU/mL) during the period of absent erythropoiesis, erythroid engraftment was observed soon after the initiation of human recombinant erythropoietin at a dose of 50 U per kg daily. This experience suggests that high dose erythropoietin may stimulate sufficient production of erythroid precursors to overcome circulating inhibitors resulting in the correction of pure red cell aplasia. PMID- 8488548 TI - Recent evolution of clotting factor concentrates for hemophilia A and B. Transfusion Practices Committee. PMID- 8488549 TI - Controversies in transfusion medicine. Blood banks should use good manufacturing practices and the pharmaceutical manufacturing approach [corrected]. PMID- 8488550 TI - Controversies in transfusion medicine. The recent emphasis on good manufacturing practices and the pharmaceutical manufacturing approach damages blood banking and transfusion medicine as medical care activities [corrected]. PMID- 8488551 TI - Continuous infusion of factor VIII concentrate to a patient with severe von Willebrand disease. PMID- 8488552 TI - On the incidence of Xga and anti-Xga in Hong Kong Chinese. PMID- 8488553 TI - Transfusion-induced anti-Ina following a single-unit transfusion. PMID- 8488554 TI - Transfusion-related acute lung injury. PMID- 8488555 TI - A putative fatty acid-binding domain of the NMDA receptor. PMID- 8488556 TI - A data-based reaction mechanism for type I fructose bisphosphate aldolase. AB - The structures of three type I fructose-1,6-bisphosphate aldolases have been determined and the common residues surrounding the Schiff base-forming Lys residue located. Armed with this information, it is now possible to propose a mechanism for this ubiquitous enzyme which is consistent with the recorded biochemical data. An interesting, but by no means mandatory, feature of the reaction mechanism is that catalysis can proceed without exchange with the solvent. PMID- 8488557 TI - The biochemical basis of the NADPH oxidase of phagocytes. AB - The NADPH oxidase is an electron transport chain found in lymphocytes and in the wall of the endocytic vacuole of 'professional' phagocytic cells. It is so called because NADPH is used as an electron donor to reduce oxygen to superoxide and hydrogen peroxide. The redox components are provided by a very unusual flavocytochrome b from the membrane, which is dependent upon cytosolic factors (including two specialized proteins, p47phox and p67phox) for activation. The small GTP-binding protein, p21rac, is also implicated in this system, possibly as the switch that triggers electron transport. This system provides a key to our understanding of the way in which these GTP-binding proteins function. PMID- 8488559 TI - Computers for molecular biologists. PMID- 8488558 TI - Nerve growth factor revisited. AB - Recent studies on nerve growth factor have revealed important new insights into the structure, function and evolution of this prototypical neurotrophic factor. Some of its features are (1) it has a unique three-dimensional fold that has since been found in two other growth factors, (2) it uses the trk proto-oncogene product, which has a tyrosine kinase, as a receptor and (3) it shares homology with at least three other factors, now collectively called neurotrophins, which have a spectrum of target cells. PMID- 8488560 TI - Numerical integration of rate equations by computer. AB - This article describes the availability of a package of free, user-friendly computer programs (VAX, PC or Mac) that allow investigators to obtain insights into reaction mechanisms. The programs provide an easy way to use the full time course of a reaction to evaluate kinetic mechanisms and determine rate constants for the transitions between the intermediates. While the programs can be used to examine any reaction mechanism, they are particularly useful for enzymatic reactions. PMID- 8488561 TI - William Arthur Johnson--a postgraduate's contribution to the Krebs cycle. AB - Anyone wishing to find out more about William Arthur Johnson will find little of relevance in the history of the Krebs cycle. Although Krebs makes fleeting reference to Johnson in his autobiography, no mention is made of Johnson's contribution in the Nobel Prize oration. Who was William Johnson and what role did he play in this crucially important work? PMID- 8488562 TI - UGA: a split personality in the universal genetic code. PMID- 8488563 TI - cDNA subtraction library construction using a magnet-assisted subtraction technique (MAST). PMID- 8488564 TI - Improved immunocytochemical detection of biotinylated probes with Neutralite avidin. PMID- 8488565 TI - Pulsed-field gel electrophoresis of Streptomyces lividans DNA. PMID- 8488566 TI - Ionizing radiation, genetic risk estimation and molecular biology: impact and inferences. AB - In recent years, a substantial amount of information has been obtained on the molecular nature of spontaneous mutations underlying human mendelian diseases, and on the mechanisms that give rise to these mutations. These data, when considered together with data on mutations induced by ionizing radiation in mammalian experimental systems, support the view that current radiation risk estimates for mendelian diseases (which are based on mouse data) are conservative. PMID- 8488567 TI - The role of host tyrosine phosphorylation in bacterial pathogenesis. AB - Recent studies on the pathogenic mechanisms of several bacterial genera, including the Yersinia, Salmonella and Escherichia, have revealed novel strategies of infection that involve the signal transduction processes of eukaryotic cells. These model systems are reviewed here, with emphasis on the role of tyrosine phosphorylation in these bacterial-host cell interactions. PMID- 8488568 TI - Turner syndrome: the case of the missing sex chromosome. AB - Turner syndrome is the phenotype associated with the absence of a second sex chromosome in humans. Recent observations support the hypothesis that the phenotype results from haploid dosage of genes that are common to the X and Y chromosomes and that escape X inactivation. A goal of current studies is the identification of these "Turner' genes. PMID- 8488569 TI - The Cheng-Prusoff relationship: something lost in the translation. AB - For a variety of reasons, pharmacologists often construct 'inhibition curves' to evaluate antagonists rather than employing the more comprehensive 'Schild analysis'. There is a widespread perception that it is only possible to derive antagonist Kb values from such experiments via application of the Cheng-Prusoff equation, requiring knowledge of the agonist affinity at the receptor. In this article, Douglas Craig presents a practical examination of 'inhibition curve' methodology and demonstrates that it is a related equation requiring no knowledge of agonist affinity, rather than the Cheng-Prusoff equation, that affords theoretically valid estimates of antagonist Kb values from this technique. PMID- 8488571 TI - The value of autopsies in hospital practice. PMID- 8488572 TI - The editors in tandem. PMID- 8488570 TI - Phospholipase A2 enzymes: regulation and inhibition. AB - The phospholipase A2 enzymes are important components of the cellular machinery that responds to inflammatory stimuli and maintains cell homeostasis by membrane remodelling. Their role as the rate-limiting step in the production of pro inflammatory lipid mediators makes these enzymes an important therapeutic target for the treatment of inflammatory disorders. Keith Glaser and colleagues explain how the two major groups of phospholipase A2, the secretory and cytosolic forms, are very different both structurally and enzymatically. Understanding the relative contributions of these different forms of phospholipase A2 to physiological and pathological conditions requires greater insight into their cellular regulation and the development of selective inhibitors. PMID- 8488573 TI - The value of the autopsy in a rural hospital of Haiti. AB - We conducted a retrospective study of the autopsies performed during a 28-month period in the Department of Medicine of the Hopital Albert Schweitzer in Haiti. We found that of 77 autopsies, the main clinical diagnosis was not confirmed at autopsy in 15 patients (19.5%). The results obtained at autopsy would have changed the treatment in 19 patients (24.7%) and the new therapeutical regimens could have had a significant impact on the outcome in six patients (7.8%). Important new information was also gained from the macroscopical examination only. The authors stress the value of the post-mortem examination in areas with limited resources. PMID- 8488574 TI - Rapid rural appraisal: its role in health planning in developing countries. AB - There is an urgent need for a quick inexpensive and reliable method for identifying groups and individuals most in need of primary health care. The Rapid Rural Appraisal (RRA) is the most appropriate approach. It is a method by which resources can be quickly deployed to alleviate the problems of the poor. If properly used it can play a major role in identifying community health needs thereby aiding the health planning process and improving the health of the people. Nevertheless, RRA techniques should not be regarded as separate and apart from other research methodologies but complementary to them. PMID- 8488575 TI - Prevention of transfusion-associated HIV transmission with the use of a transfusion protocol for under 5s. AB - Recently there has been an increasing realization that for the prevention of transfusion-associated HIV infection, HIV screening alone is insufficient. In 1988, a treatment protocol for children under 5 years with severe anaemia, was introduced in Ekwendeni Hospital. Initial results showed that it was possible to reduce the number of blood transfusions without increasing the mortality rate. By January 1992 the protocol was being widely disregarded by ward staff, and transfusion rates had increased. Strict enforcement of the transfusion protocol from the 16 January produced a sharp drop in the percentage transfused from 44% to 11%. Mortality rates remained similar throughout the period of the study. Thus, it would appear to be possible, with the use of the transfusion protocol, to reduce the number of blood transfusions carried out, without affecting mortality rates, and hence to reduce the risk of transfusion-associated HIV. PMID- 8488576 TI - Bicycle injuries in a tropical city (Townsville) PMID- 8488577 TI - Reusable needles--a major risk factor for acute virus B hepatitis. AB - We conducted a case control study to find the extent to which acute virus B hepatitis was hospital acquired. One hundred and sixty consecutive cases of acute virus B hepatitis were compared with age (+/- 3 years) and sex matched healthy hospital visitors. Exposure to reusable needles, blood or blood products, therapeutic and diagnostic procedures, common razors and sexual practices were elicited by means of a questionnaire. Only exposures in the incubation period (6 weeks to 6 months before the onset of symptoms) were included in the analysis. The odds ratio (OR) for injections for reusable needles was 6.3 [95% confidence interval (CI) = 3.8-10.6]. The OR for single injection (OR = 3.9; 95% CI = 2.0 7.3) was less than that for multiple injections (OR = 9.8; 95% CI = 3.8-26.3), showing a dose response relationship. The proportion of cases of acute virus B hepatitis attributable to hospital related exposures was 67%. Proper aseptic techniques and sterilization practices can substantially reduce the incidence of acute hepatitis B in the population. PMID- 8488578 TI - Estimating maternal mortality by sisterhood method in rural Zimbabwe. PMID- 8488579 TI - Osmotic production of sterile oral rehydration solutions--an economic, low technology method. AB - A sterile oral rehydration solution can be produced by immersing in water a semi permeable cellulose tube containing glucose and salts. Osmotically-driven ultrafiltration excludes all microbes and particulate matter even when the immersion water contains 45 x 10(6) cfu/ml of Pseudomonas aeruginosa, 25 x 10(7) cfu/ml of Staphylococcus aureus or 20 x 10(7) cfu/ml of Escherichia coli. Solutions of consistent composition can be obtained by having a standard amount of glucose-electrolytes in a cellulose tube of appropriate dimensions and immersing this in a fixed volume of water for a minimum period of time. The method is simple, inexpensive, low-technology and requires no external source of power. It has potential for producing sterile solutions for injections and intravenous use in situations with very limited and simple resources, in emergencies and during natural disasters. Further studies are now needed to determine whether the method can be adapted to provide the large quantities of oral rehydration fluid needed in field conditions. PMID- 8488580 TI - External skeletal fixation: experience in a small rural hospital in northern Kenya. AB - The author describes the use of external skeletal fixation in the management of complicated septic limb fractures. Eight fractures in seven patients were treated at Sololo General Hospital using a low cost, simple external device, with good results. The report emphasizes how external fixation can solve difficult fracture cases in small up-country hospitals; a good example of appropriate technology at district level. PMID- 8488581 TI - Blast injuries of the eye. AB - Ninety-four cases of ocular blast injuries (122 eyes) were studied. Sixty-five per cent of the cases were between 15 and 25 years of age. The right and the left eyes were involved in 38% and 32% of the cases, respectively, while bilateral involvement was seen in 30%. Ninety of the eyes (74%) were blind. Twenty-one per cent of the patients with binocular injuries had bilateral blindness. Injuries of the iris, conjunctival and corneal foreign-bodies, and corneal and/or scleral lacerations were the most frequent types of injury seen. PMID- 8488582 TI - Paraprofessional women as health care facilitators in mother and child health. AB - The aim of the study was to compare the performance of midwives with that of lady home visitors (LHV; paraprofessionals). The project area was divided into six according to the population map. One midwife or one LHV was assigned to each visiting area. Home visits were carried out to identify and offer guidance on family planning (FP), antenatal care, well-child control, immunizations and other mother and child health related issues to those at high risk. Criteria taken for evaluation were the numbers of pregnant women identified in the last trimester; pregnant women receiving antenatal care; deliveries attended by a health care provider; modern FP users; continuation rate of the new users; pregnancy rate in new users; immunization status of children; well-child visits of the children. No significant differences were found in these health measurements between areas visited by LHV and areas visited by midwives. Response rates to the invitation was also similar in both areas. An important observation was the good performance of the LHV in communicating with the families. Women with limited school attainment from the community can be used effectively and efficiently in community health services. PMID- 8488583 TI - Another look at acute appendicitis in tropical Africa: and the value of laparoscopy in diagnosis. AB - Acute appendicitis is believed to be one of the commonest causes of the acute abdomen in tropical Africa. Negative appendicectomy rates are usually above 20%, which is now considered unacceptably high because of increased risk to patients and the availability of diagnostic facilities to aid clinical decision-making. Our negative appendicectomy rate over a 4-year retrospective period was 29.7% in males, and 47% in females. These reduced to 11% and 10%, respectively, after the introduction of laparoscopy for doubtful cases of acute abdominal pain. PMID- 8488584 TI - Leprosy in Botswana. PMID- 8488585 TI - Pancreatic pseudocysts in children: a Zimbabwean perspective. PMID- 8488586 TI - L'Institut Panafricain de Sante Communautaire: a new initiative in the training of health professionals in community health in French speaking Africa. PMID- 8488587 TI - Improving drug utilization: what about the 'KAP' gap? PMID- 8488588 TI - Inserting a Sengstaken-Blakemore (S-B) tube. PMID- 8488589 TI - Nasogastric tube knotting: spontaneous or induced? PMID- 8488590 TI - 0.1% lignocaine with 1:1000,000 adrenaline in general surgery. PMID- 8488591 TI - Ascariasis and post-operative recovery. PMID- 8488592 TI - Retroperitoneal sponge causing painless haematuria. PMID- 8488593 TI - Mycotic aneurysm of the brachial artery simulating soft tissue malignancy. PMID- 8488594 TI - Rabies vaccine: economical regimens. PMID- 8488595 TI - [Urinary incontinence--a problem neglected by physicians?]. PMID- 8488596 TI - [Urinary incontinence after apoplexy]. AB - In a retrospective study, based upon doctors' and nurses' case records, urinary incontinence (UI) and its relation to the severity of strokes was studied in 156 stroke patients discharged from the department of neurology, Bispebjerg Hospital in 1988. A significant relationship was found between the presence of UI and stroke severity measured by length of hospital stay, circumstances of discharge and mobility (p < 0.0001). 44% of patients had some urinary incontinence on admission and on discharge 26% still had UI. Surprisingly, however, information about incontinence appeared in only 10% of doctors' records, whereas nurses, records had the relevant information concerning as many as 90% of patients. It appears that urinary incontinence in stroke patients has a low priority among doctors. PMID- 8488597 TI - [Measurement of stress and stressors in epidemiological studies]. AB - There is considerable uncertainty and confusion with regard to definitions and measurements of stress and stressors in the medical literature. In the present article the concepts are defined, and three different methods for measuring stress and stressors respectively are presented. A matrix constructed against this background is used to classify a number of studies on stressors, stress, and disease. On the basis of examples from empirical studies, methodological problems are discussed. It is concluded that the methodological problems within this field of research are not fundamentally different from the wellknown methodological problems of medical epidemiology. It is recommended that independent measures of stressors as well as stress are used as widely as possible. PMID- 8488598 TI - [Invasive fibrous thyroiditis--Riedel's goiter. A review of the literature and a case report]. AB - Invasive fibrous thyroiditis (Riedel's goitre) is a rare condition of an unknown aetiology. The condition was first described by Riedel in 1883. In 1904 Hashimoto described another condition of invasive fibrous thyroiditis. Since then it has been discussed if Hashimoto's thyroiditis and Riedel's goitre were one disease in different states or two different diseases. Hashimoto's thyroiditis is known to have an autoimmune aetiology and it can be seen together with pernicious anaemia. Co-existence of Riedel's goitre and pernicious anaemia has never been reported. The patient mentioned had both Riedel's goitre and pernicious anaemia, and was first treated with subtotal thyroidectomy, relapsed after one year and consequently received steroids. Such coexistence and the very good effect of steroids could be explained on the basis of Hashimoto's and Riedel's thyroiditis being one condition in different states and with an autoimmune aetiology. It is recommended that patients with Riedel's goitre are postoperatively treated with steroids. PMID- 8488599 TI - [Electron microscopy of needle biopsies from cancer patients with unknown primary tumors]. AB - The aim of the present study was to evaluate the diagnostic value of electron microscopy (EM) performed on Surecut biopsies from patients without known primary tumour. The material consisted of 108 consecutive biopsies, obtained over a period of two years, from patients with tumour(s) in the liver or lymph nodes (on the neck, in the axilla or retroperitoneum). From each patient fine needle aspirations and Surecut biopsies for light microscopy and electron microscopy were taken. Only biopsies in which material for both electron microscopy and light microscopy was sufficient were included (60%). Immunohistochemical reactions were performed on paraffin sections when indicated. Final diagnoses were confirmed on surgically removed specimens and/or autopsies. Electron microscopy was necessary for obtaining the final histological diagnosis in 15% of the cases. It is therefore recommended to obtain additional ultrasound guided biopsies for EM from cancer patients with tumours in the liver or lymph nodes in cases where the primary origin of the tumour is unknown. PMID- 8488600 TI - [Assessment of sex life and psychological reactions after local excision of vulvar carcinoma in situ]. PMID- 8488601 TI - [Evaluation of knemometry as a method for control of growth in short-stature children during a single-year treatment with growth hormone]. PMID- 8488602 TI - [Toxic epidermal necrolysis]. AB - A case of severe toxic epidermal necrolysis is described, stressing the importance of multiorgan system involvement of the disease. A possible pathogenetic mechanism involving tumor necrosis factor is discussed. PMID- 8488603 TI - [Physiology of growth hormone during pregnancy]. PMID- 8488604 TI - [New targets for anti-ulcer agents?]. PMID- 8488605 TI - [Sexual knowledge among physicians of women applying for abortion]. PMID- 8488606 TI - [Quality assurance and legal position of physicians]. PMID- 8488607 TI - [Can Q-10 be dangerous?]. PMID- 8488608 TI - Staging of early prostate cancer: a proposed tumor volume-based prognostic index. AB - Current staging of early prostate cancer separates patients into two groups: those with palpable and non-palpable tumors. Such staging relies on digital rectal examination in making this separation, despite the low sensitivity, low specificity, and low positive predictive value of this method. As an alternative, tumor volume may be useful for staging because of its powerful prognostic ability and its potential to be assessed clinically due to recent advances in imaging techniques such as transrectal ultrasound. In this study, we evaluate the utility of tumor volume in predicting progression of early prostate cancer based on the composite published evidence from nine pathologic studies of serially-sectioned prostates. Logistic regression revealed that tumor volume was a good positive predictor of all measures of tumor progression. There was a 10 percent probability of capsular invasion in tumors measuring about 0.5 cm3; 10 percent probability of seminal vesicle invasion in tumors measuring about 4.0 cm3; and 10 percent probability of metastases in tumors measuring about 5.0 cm3. These composite results suggest that tumor volume is a significant predictor of cancer progression. A volume-based prognostic index is proposed as an adjunct to staging for early prostate cancer. PMID- 8488609 TI - Use of tissue expanders in final reconstruction of infrapubic midline scar, mons pubis, and vulva after bladder exstrophy repair. AB - Two patients following bladder exstrophy repair presented for final cosmetic reconstruction with the characteristic lower abdominal midline scar, bisected mons pubis, and laterally displaced labia majora. Tissue expanders were used to obtain additional skin and subcutaneous tissue. After adequate serial expansion, the expanders were removed, scar tissue excised, and primary approximation of healthy tissues performed. A tension-free closure and esthetically pleasing midline incision, mons pubis, and vulva were obtained. PMID- 8488610 TI - Potentiation of drug-induced erection with audiovisual sexual stimulation. AB - Twenty-five patients underwent audiovisual sexual stimulation (AVSS) after pharmacologically-induced erection. Grade of erection and cavernosal blood flow were assessed after intracorporeal (IC) injection of TRI-MIX or prostaglandin E1, and then after AVSS, using pulsed Doppler ultrasonography (PDUS). After IC injection, 5 patients had a Grade II erection, 8 had Grade III, 10 had Grade IV, and 2 had Grade V. There was an increase in peak arterial flow and arterial diameter which corresponded with the grade of erection obtained. After addition of AVSS, 56.5 percent of patients experienced improved erection. The improvement from Grade III to IV in 13 percent is especially significant because it showed the attainment of adequate erection when IC injection alone failed. Penile blood flow improved among AVSS responders but not in nonresponders. AVSS may enhance pharmacologically-induced erection and may improve the diagnostic accuracy of PDUS. PMID- 8488611 TI - Pheochromocytoma of urinary bladder: contemporary methods of diagnosis and treatment options. AB - Two patients with vesical pheochromocytoma are presented with a review of the literature. Imaging modalities for localizing extra-adrenal pheochromocytomas are reviewed with an overview of the commonly accepted treatment options. Successful treatment of this lesion requires a high index of suspicion based upon the patient's symptom complex, allowing preoperative preparation prior to surgical manipulation. PMID- 8488612 TI - Renal angiomyolipoma in association with pulmonary lymphangioleiomyomatosis: forme fruste of tuberous sclerosis? AB - From 1976 to 1989, 27 patients with pulmonary lymphangioleiomyomatosis were seen at our institution. Twenty-five had no signs or symptoms of tuberous sclerosis; 21 of these had abdominal imaging or surgical exploration to make the diagnosis of renal angiomyolipoma in seven patients, all female. Three presented with symptoms secondary to renal disease, three with pulmonary manifestations, and one with both. Renal disease was bilateral in four patients; four patients underwent nephrectomy and two tumors were embolized. All patients experienced spontaneous pneumothoraces during the course of their disease. There was one respiratory death. It is our belief that any patient presenting with angiomyolipoma and a history of pulmonary problems should be evaluated for pulmonary lymphangioleiomyomatosis with a limited computed tomography scan of the chest at the time of abdominal imaging. The surgical treatment of angiomyolipoma when associated with lymphangioleiomyomatosis is predicated on the ability to adequately manage the complicating lung disease perioperatively. PMID- 8488614 TI - Renal cell carcinoma with situs inversus totalis. AB - A case of renal cell carcinoma in a patient with situs inversus totalis is reported. Only 8 cases of malignant neoplasms have been reported in situs inversus totalis, and our case represents the second case report of renal cell carcinoma in a patient with situs inversus totalis. The frequency of situs inversus totalis is between 1 in 8,000 and 1 in 20,000. Cardiac and pulmonary anomalies are common in patients with situs inversus totalis. Renal anomalies, including agenesis, dysplasia, hypoplasia, ectopia, polycystic kidney, and horseshoe kidney, have been reported. Because of the association between situs inversus and cardiac, pulmonary, renal, and vascular anomalies, management of the patient with situs inversus and urologic disease requires careful preoperative evaluation. PMID- 8488613 TI - Evaluation of erectile dysfunction by dynamic infusion cavernosometry and cavernosography (DICC). Multi-institutional study. AB - In a cooperative, private practice, multi-institutional impotence study, dynamic infusion cavernosometry and cavernosography (DICC) was performed on 743 patients to make an accurate diagnosis and/or identify candidates for penile revascularization. Maximum equilibrium intracorporeal pressure achieved following papaverine and phentolamine injection (Phase I) averaged 29.42 +/- 0.76 mm Hg, approximately one third of normal erection pressure. Corporeal pressure fall from 150 mm Hg over thirty seconds (cavernosometry) averaged 82.38 +/- 1.33 mm Hg (Phase II). The gradient between systolic and cavernosal artery pressure averaged 42.84 +/- 1.12 mm Hg on the right and 43.33 +/- 1.13 mm Hg on the left (Phase III). Cavernosography at 90 mm Hg erection pressure was performed in Phase IV. Of the 124 patients from one center who were reviewed in greater detail, pure cavernosal artery insufficiency (CAI) was found in 25 (20.2%), corporeal veno occlusive dysfunction (CVOD) in 26 (21.0%), and 73 patients (58.9%) demonstrated combined CAI and CVOD. Diabetics (n = 69) achieved lower equilibrium intracorporeal pressures than nondiabetics, had similar CVOD, and worse CAI. Smokers (n = 365) and patients with Peyronie's disease (n = 32) had erectile dysfunction similar to those without these conditions. Patients impotent after trauma (n = 124) were younger, achieved higher intracorporeal pressures, and showed better corporeal veno-occlusive function than those without trauma. Complications of DICC were minimal and infrequent. After DICC, 169 patients underwent internal pudendal arteriography, 105 had arterial bypass surgery with or without penile venous ligation procedures, and 45 had venous surgery alone. Dynamic infusion cavernosometry and cavernosography is a useful erectile function study to evaluate impotence and can be performed easily in a private practice setting. PMID- 8488615 TI - Clostridium perfringens emphysematous cystitis. AB - Emphysematous cystitis is a rare disease and is usually caused by aerobic bacteria, most commonly Escherichia coli. Only rarely have anaerobic bacteria been associated with this condition. We report a case of emphysematous cystitis due to Clostridium perfringens with bacteremia in an elderly diabetic woman. PMID- 8488616 TI - Varicoceles: effect on testicular volume in prepubertal and pubertal males. AB - A total of 63 prepubertal and 17 pubertal males were examined to determine both testicular volumes and to correlate testicular volumes with the presence or absence of a varicocele. In the prepubertal group neither the left nor the right testicle predominated in size. In the pubertal group, the left testicle with an associated varicocele was smaller than the right. PMID- 8488617 TI - Malignant melanoma of penis and male urethra. Is it a difficult tumor to diagnose? AB - Two cases of malignant melanoma of the penis and male urethra are presented in which the diagnosis was difficult to make clinically and histopathologically. Our findings support the general opinion that melanomas at this site have a poor prognosis. PMID- 8488618 TI - Instrument for ligation of dorsal vein complex in radical prostatectomy. PMID- 8488619 TI - Comparison of vasovasostomy techniques in rats utilizing conventional microsurgical suture, carbon dioxide laser, and fibrin tissue adhesives. AB - An evaluation of vas reanastomoses in rats comparing suture only, carbon dioxide (CO2) laser-assisted, and fibrin-based tissue adhesive was performed in our laboratory. A cohort of 60 known fertile male Sprague Dawley rats initially underwent lower midline abdominal exploration and transection of their vas deferens bilaterally, followed by immediate microsurgical vasovasostomy by one of the three experimental methods. All groups initially had the severed vasa ends coapted by two or three transmural (mucosa through serosa) sutures of 10-0 nylon under an operating microscope. The conventionally sutured group had an additional four to six nylon 10-0 sutures placed externally in the serosa only to complete the anastomosis. The CO2 laser-assisted group underwent laser welding with denaturation of the serosa to seal the anastomosis. A fibrin-based tissue adhesive, produced by combining human cryoprecipitate and thrombin, was placed topically over the coapted vas ends to seal the anastomosis in the third group. Postoperative evaluation revealed similarities among the three surgical groups with the fibrin-based tissue adhesive group resulting in the highest patency rate (89%) and pregnancy rate (85%) as well as the lowest granulation rate (18%) and shortest operative time (27 minutes). The laser-assisted group resulted in the lowest pregnancy rate (68%), while the sewn anastomosis group had the lowest patency rate (76%). Both laser-assisted and conventionally sewn vasectomy reversals required significantly longer operative time (39 and 46 minutes, respectively) compared with the fibrin-based tissue adhesive-assisted procedures (p < 0.01). This study provides evidence that alternative microsurgical techniques may be utilized to perform uncomplicated, expeditious, and successful vasectomy reversals. PMID- 8488620 TI - Effect of nifedipine on kidney and ureteral function after experimental acute unilateral ureteral obstruction. AB - Nifedipine, a calcium channel blocker, was tested for its in vivo effect on the ureter and kidney during acute obstruction. There was no discernible effect on peristalsis but glomerular filtration rate was improved. Thus, nifedipine would not be expected to decrease renal colic from obstruction. PMID- 8488621 TI - Effect of lidocaine on ureteral motility and fluid transport in vitro. AB - We used a whole canine ureter, under constant inflow hydrostatic pressure, in a tissue bath, to investigate the effect of lidocaine on flow and contractility in the ureter, simultaneously. Lidocaine caused increased contractility and reduction of flow in 9 ureters tested. In 5/9 ureters exposed to lidocaine in concentration of 50 to 500 micrograms/mL in the bath, the contraction became continuous and the flow ceased. This could be reversed by irrigating the bath with fresh solution. We conclude that lidocaine causes increased contractility and reduction of flow in canine ureters in vitro. PMID- 8488622 TI - Isolated lymphoma of genitourinary tract and adrenals. AB - With the routine use of computed tomographic imaging, intrinsic involvement of the genitourinary tract in newly diagnosed non-Hodgkin's lymphoma is seen in as many as 10 percent of patients. Incidental discovery of an extranodal, extra lymphatic lesion in the genitourinary tract without clinical or radiographic evidence of disease elsewhere, however, is an uncommon occurrence. The clinical presentation and imaging findings in 4 patients with initial manifestation of lymphoma isolated to the kidney, ureter, bladder, and adrenals, respectively, are presented. These patients had no evidence of lymphoma elsewhere, and imaging studies mimicked the more common neoplasms affecting these organs. PMID- 8488623 TI - Magnetic resonance images of hematospermia. AB - Seminal vesicles and their adjacent structures were studied using magnetic resonance imaging (MRI) in 7 normal volunteers and 15 patients with hematospermia. Normal seminal vesicles are depicted on T2-weighted images either as a mixture of high- and low-signal granules or as a convolution of tubules with a diameter of less than 0.5 cm. Fourteen of the 15 patients with hematospermia exhibited abnormalities on MRI. Dilatation or cyst formation in the seminal vesicle was observed in 13 patients, and a dilatation of the midline structure was seen in 3 patients. Abnormal signal intensity of the seminal vesicles was seen in 11 patients and was thought to be due to subacute hemorrhage. PMID- 8488624 TI - [Functional level, care needs and family-based care for home-care recipients with extended care needs]. AB - A study of home care and home health services was undertaken in three Swedish municipalities. Persons who received extended home care and home health care were interviewed. The interviews covered different themes such as impairments, care needs, functions and activities in the horizontal social network (the informal network), and opinions concerning how care is and should be provided. A modified ADL-index was used to assess the functional level of daily living. Care needs were measured by the judgement of the care recipient, and by the interviewer's judgement. The correspondence between these measures was high, with some exceptions. Lower correspondence between the measures was obtained for three categories of care recipients: individuals with communicative dysfunctions, younger individuals with reduced ability to move and, thirdly, individuals with psychosocial problems. Problems concerning measurement of care given by family members were also identified and discussed. PMID- 8488625 TI - Emotions, care and particularity. AB - The main intention of this article is to illuminate the normative foundation of caring in nursing. I will focus on the debate between an ethics of care and an ethics of universal principles which has evolved both in nursing ethics and moral philosophy during the last decade. In spite of what a number of people have claimed, I shall argue that a care-based ethics is compatible with judgment based on universal, impartial principles. However, an ethics of care articulates other important aspects of morality and moral behavior than the justificational ones that are central to prevailing impartialist ethics. The paper explains why and how moral perception, sensitivity and emotional capacities are important for a modern professional nursing ethics. It focuses on capacities and preconditions for principle-based reflection and action by arguing that moral perception and certain emotional qualities are prerequisites for moral judgment and action. Achieving perceptual awareness and emotional sensitivity in understanding the situation and its particulars are genuine moral tasks in nursing. These qualities are essential in discovering the morally salient features of the situation. This perspective on an ethics of care also recognizes an important place to central positions in traditional nursing ethics, where developing personal qualities and altruistic capabilities have always been a fundamental normative claim. PMID- 8488626 TI - [Why situational ethics in many cases can be right for clinical nurses and other health workers]. PMID- 8488627 TI - Nursing home staff opinions of work with demented patients and effects of training in integrity-promoting care. AB - This study is part of a larger study of the effect of integrity-promoting care in a Swedish nursing home ward. Compared with assessments on a control ward, improvements were found in the patients' behaviour and in the quality of care after a three-month intervention period. This paper reports on parts of a questionnaire survey on the nursing staff's opinions of their working conditions and demented patients. Most staff members on both the intervention ward and the control ward found their jobs meaningful, engaging and stimulating, but they also felt that they had a heavy work-load. Most of the staff members experienced mental strain because of the patients' disturbed behaviour. Many did not think that the care on their ward would have been good enough for their own close relatives, if they had been suffering from dementia. Only slight changes were found in the staff members opinions after the intervention. PMID- 8488628 TI - [Properties of adherent staphylococci isolated from the rumen wall in lambs]. AB - Six defined strains of adherent, coagulase-negative and catalase-positive staphylococci were isolated from the rumen wall of lambs. All the strains fermented maltose and had positive acetoin production. The strains were classified as follows on the basis of diagnostic tests, according to an identification key: three strains belonged to the species Staphylococcus warneri (SW34, SW64, SW6), two to the species S. epidermidis (SE30, SE49) and one to the species S. cohnii subsp. urealyticum (SCU32)--Tab. I. The adherence index of the different isolates ranged from 1.9 +/- 0.02 to 14.9 +/- 2.12 of bacteria adhering to one epithelial cell of the rumen wall. There were large differences in urease production (2.3 +/- 0.15 to 29.3 +/- 1.16 nkat/ml). But in general the isolated staphylococci can be taken as strains with low, medium or high adherence, and/or urease activity (Tab. II). In the group of facultative anaerobic bacteria the staphylococci are the first, lactic acid producing bacteria and the attained production (0.164 to 0.687 mol/l) is adequate to their portion in the rumen (Tab. II). The isolated strains produced bacteriocin-like substances which inhibited the growth of maximally four out of the six used indicator bacteria of the same species, and also of a related species (Tab. III) while they showed small but clear zones of inhibition of the size 2 to 5 mm. In general, the mentioned staphylococci can be considered as little active producers of bacteriocin-like substances. All the tested strains were resistant to the observed heavy metals. PMID- 8488629 TI - [Acute oral toxicity of bentazon, an herbicide developed in Czechoslovakia, in pheasants and rabbits and the clinical symptoms of poisoning]. AB - Adult rabbits of the New Zealand White breed and pheasants were used to determine the rate of acute oral toxicity (LD50), clinical symptomatology of poisoning of organisms loaded with lethal doses, and the recovery of intoxicated individuals from the toxic effects of bentazon, Czechoslovak developmental herbicide (Research Institute of Chemical Technology, Bratislava), administered at sublethal doses within the framework of obligatory toxicological testing of this herbicide. The determined acute oral toxicity (LD50) was 1139 mg/kg in rabbits and 2918 mg/kg of live weight in pheasants. The table shows LD50 of the tested herbicide for various animal species. The LD50 values of bentazon produced abroad (Germany) are also shown for comparison in this table. If the LD50 values of both herbicides are compared, Czechoslovak developmental bentazon appears safer. The administration of lethal doses (1110 and 1170 mg/kg in rabbits, 2750 and 3100 mg/kg of live weight in pheasants) resulted in clinical symptoms of poisoning detected predominantly in the respiratory system. Shallow accelerated breathing and dyspnoea, CNS suppression, pronounced increase in body temperature, rapid onset and high intensity of rigor mortis were observed. Animals which died as a result of asphyxia induced by the sublethal doses (1000 mg/kg in rabbits and 2200 mg/kg in pheasants) were observed after 2-4 days. Difficult accelerated breathing and increased body temperature disappeared after 1-2 days while the remaining symptoms after 2-3 days. The loss of appetite persisted for 2-4 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488630 TI - [Occurrence of Leptospira antibodies in the blood of game animals]. AB - The blood serum of game was examined for the presence of antibodies to Leptospiras in 1987-1989. A total of 792 blood sera from animals belonging to 14 zoo-species were examined (Tab. I). The blood serum of red deer (Cervus elephus) was examined the most often within the group of animals, in 398 cases, i.e. 50.2%, followed by 165 blood sera of wild boar (Sus scrofa), representing 20.8%, and by 136 blood sera of roedeer (Capreolus capreolus), representing 18.6%. Small numbers of blood sera of the other animals were examined. A serological reaction of microagglutination-lysion revealed the antibodies to Leptospiras in fifty examined samples, i.e. 6.31%, of the six examined zoo-species: muskrat (Ondatra zibethica) 14.28%, wild boar (Sus scrofa) 13.93%, roedeer (Capreolus capreolus) 6.76%, fox (Vulpes vulpes) 5.26%, red deer (Cervus elephus) 3.76%, mouflon (Ovis musimon) 2.50%. No antibodies to Leptospiras were found in the blood serum of the other animal species (Tab. I). Twelve strains of Leptospira were used for serological examination according to the standard method (Sebek, 1979). The examined blood sera of game reacted only with Leptospiras of the serotype L. grippotyphosa. No reaction with other Leptospira serotypes was observed. Our results have demonstrated, in comparison with the results of foreign authors, great susceptibility of the game to infection with different serotypes of Leptospira. But it is possible to say that with certain exceptions these game species do not play an important role in the epidemiology of Leptospirosis. PMID- 8488631 TI - [Occurrence of streptococci resistant to antibiotics in the rumen of calves]. AB - The occurrence and antibiotic-resistance spectrum of some strains of rumen streptococci were investigated in calves of four age categories in the milk diet period at 1-3, 4-7, 8-14 days of age and 6-8 weeks of age. More than 75% of the strains isolated from the calves of all age categories were resistant to more than one tested antibiotic (tetracycline, neomycin, erythromycin, streptomycin, chloramphenicol). The average number of streptococci isolated from the ingesta of calves during the period of observation was 10(5) per ml. The per cent of resistant strains showed an increasing trend from birth to the age of 8-14 days (Tab. I). The occurrence of resistant strains in 6-8 week calves was even lower than in the calves of the youngest age category. A four-marker type of resistance (41.6-50%) prevailed within 14 days of age. Two-marker types of resistance (42.6%) occurred most frequently in the calves of the oldest age category. Tab. II shows the spectrum of resistant strains. Tetracycline-resistant amylolytic strains of Streptococcus bovis were selected from among the isolated strains to be used as donor strains in conjugation experiments. Successful resistance transmission was observed in solid-surface conjugation. The transmission frequency ranged within the transconjugate values of 10(-3) to 10(-5) per donor cell within the species (Tab. III). A chromosomally rifampicin-resistant strain of Streptococcus bovis BM114 was used as a recipient as it did not contain any plasmids and was sensitive to the tested antibiotics. Agarose-gel electrophoresis was used to visualize the presence of plasmid DNA in donor strains (Fig. 1). PMID- 8488632 TI - [A rapid method of detecting psychrotrophic bacteria in raw milk]. AB - Determination of the counts of psychrotrophic bacteria offers an important indicator of the technological quality of purchased raw milk, and also an indicator of the hygienic level of its production in agricultural primary production, particularly with respect to the sanitation of milking machines. The applied and published methods of determination of the counts of psychrotrophic microbial contaminants have revealed large differences, multiplied by insufficient legislation in this country, by vague and even wrong definition of the given group of bacteria, and/or by the misuse of the concepts psychrotrophic and psychrophil bacteria. Since the level of the microbial quality of raw milk should be increased, we investigated and developed convenient methods of determination of psychrotrophic bacterium counts in the last years (Urbanova et al., 1988; Urbanova, in print): these methods should facilitate the reasonable control applying an expeditious procedure. A long incubation time of standard procedure is a disadvantage complicating the practical use of the previous procedure (10 days at a temperature of 7 degrees C). An accelerated procedure of psychotrophic bacterium cultivation to determine their counts in raw milk is described in this paper. After thorough stirring, a raw milk sample is diluted with sterile physiological solution (pH 7.2) pursuant to the standard CSN 57 0101. The dilutions 10(-2), 10(-3), 10(-4) were the most convenient for inoculation when the counts of psychrotrophic contaminants were determined in raw milk. The dilutions 10(-3), 10(-4), 10(-5) were inoculated if higher milk contaminations were expected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488633 TI - [Ethologic determinants of maternal behavior in swine]. AB - Care giving behaviour was investigated in pigs as a form of maternal behaviour and its effects on the youngs. The objective of observation was to compare the identified phenomena in their biological, social and experience variables of the behaviour of the investigated animals. The observations included 40 sows and 280 youngs of the Landrace x Large White breed, of the female sex. They took place in semi-natural conditions while the standard criteria of management were maintained. Two categories of sows and their youngs were investigated. The first group included 20 sows (first-litter gilts) and their youngs: A (1-20). A study unit comprised one sow and seven youngs. The other category, B (1-20), had analogical numbers of individuals but the sows were after their third parturitions. As an indicator of maternal behaviour the average index of sociability (IS) had the value mean = 1.7 for the first category and the value mean = 2.0 for the second category. Evaluation of these differences enables to determine a significant difference between the average IS for both groups (Fig. 1). This fact, which spoke in favour of B (1-20) group, made us follow the different litters. That means we wanted to know how the maternal behaviour determined piglet sociogenesis. IS was calculated from the average values of IS determined in both categories within their adequate litters. The value mean A (a g) = 1.8 was determined for the first category (Tab. II) while for the second category B (1-20) the value mean B (a-g) made 2.0 (Tab. III).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488634 TI - Average testosterone levels in bulls after GnRH stimulation at breeder bull rearing stations and A. I. stations. AB - Base average testosterone levels and testosterone levels in 60 and 90 min after GnRH administration were determined in bulls at five breeder bull rearing stations at their age of 13 months and at nine A. I. stations at their age of 17 34 months. Significant increases in testosterone levels in 60 and 90 min after GnRH administration were the responses of all groups of bulls. There were differences between the average testosterone levels typical of the various BRSs and AISs. Highly significant correlation coefficients 0.344 for base levels and 0.583 for induced levels were calculated from a comparison of the testosterone levels determined at BRSs at the bull's age of 13 months and of those recorded after a six-month stay of the same bulls at AISs. A decrease in testosterone levels was also observed. PMID- 8488635 TI - [Mineral metabolism in calves during periods of milk feeding and weaning based on selected parameters in the blood]. AB - Concentrations of calcium, inorganic phosphorus, magnesium, sodium and potassium (Tab. I) were followed in the blood serum of calves in the period of milk diet and weaning (at the age of nine weeks), and the results were evaluated with respect to their deviations from the reference values. The average concentrations of calcium and inorganic phosphorus did not show any significant variations and they were within the range of reference values. Magnesium concentrations in the blood serum of calves on all-vegetable diet (11 weeks of age) were significantly higher (p < 0.01) in comparison with the starting value (at the age of two weeks) while they approached the lower boundary of reference range as late as at the age of nine weeks (Fig. 1). The highest percentage of hypocalcaemia (33.3%) and hypophosphataemia (47.3%) in individual animals was determined at weaning. The highest level of hypomagnesaemia was observed at the age of two and five weeks (57.1% of the calves). The subnormal values of the mentioned parameters were markedly adjusted in the calves on all-vegetable diet (Fig. 2). The concentrations of serum sodium and potassium (Fig. 3) were decreasing in the calves on milk diet, but after weaning they were stabilized at the values which were recorded at the age of five weeks (Na 146.3 mmol/l and K 5.19 mmol/l). With the exception of weaning, the average sodium concentrations in the blood serum of calves were slightly above the upper boundary of the reference range, their significant drop was observed only at weaning (p < 0.05). The concentrations of serum potassium were within the range of reference values except the values at the age of two weeks and the potassium concentrations in the serum were significantly lower at the age of 5, 9 and 11 weeks in comparison with the starting value (p < 0.01). The highest percentage of hypernatraemia (81%) and hyperkalaemia (85.7%) was determined in individual animals at the age of two weeks (Fig. 4). PMID- 8488636 TI - [Use of selected parameters in the serum and blood of calves in the evaluation of nitrogen and energy metabolism]. AB - Concentrations of total proteins, albumin, total serum immunoglobulins, urea and total lipids in the blood serum and glucose concentrations in the blood were investigated in the periods of milk nutrition and weaning, and the results were evaluated with respect to their differences from the range of reference values. Concentrations of total proteins (TP) in the blood serum significantly decreased if the starting values at the age of two weeks (65, 45 g/l) were compared with the values at the age of five weeks, and they began to increase to the age of 11 weeks. The average TP values at the age of 11 weeks were significantly higher (p < 0.01) than the starting values (Fig. 1, Tab. I). TP concentrations were above the upper limit of the reference range since weaning (nine weeks of age). Subnormal TP values were recorded in individual animals at the age of two, five weeks, at weaning, at 11 weeks in the animals on all-vegetable diet in 4.8%, 19.1%, 4.8% and 9.5% of the calves, respectively (Fig. 2). The albumin concentrations were increasing from the age of five weeks but the changes in the values were statistically insignificant and the average values remained in the reference range (Fig. 1). The reduced albumin concentrations were recorded in individual animals in 28.6% of the calves at the age of two weeks, in 19.1% of the calves at the age of five weeks, in 42.9% of the calves at weaning, and in 38.1% at the age of 11 weeks. The concentrations of total serum immunoglobulins (TS-Ig) were increasing since the animal collection with their growing age (Fig. 1) while in comparison with the starting values the increases were significant at the age of five weeks (p < 0.05), nine and eleven weeks (p < 0.01). The average TS-Ig values rose to the reference range at the age of five weeks. In individual animals, the reduced TS-Ig values were recorded in the serum at the age of two weeks in 71.4% of calves, at the age of five weeks in 42.9%, at weaning in 33.3% and at the age of 11 weeks it was only in 9.5% of the calves (Fig. 2). The urea concentration in the serum was decreasing from the age of five weeks to weaning. In comparison with the starting values, the differences in the average values were statistically insignificant and the average values remained within the reference range (Fig. 1).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488638 TI - Dogs and human epilepsy. PMID- 8488637 TI - [Sampling of venous blood and fixation of lower abdominal vessels in dairy cows]. PMID- 8488639 TI - Veterinary pathology and the Royal College of Pathologists. PMID- 8488640 TI - A comparison of lincomycin hydrochloride and clindamycin hydrochloride in the treatment of superficial pyoderma in dogs. AB - Thirty dogs with superficial pyoderma were randomly allocated to treatments with either lincomycin hydrochloride (22 mg/kg twice daily) or clindamycin hydrochloride (11 mg/kg once daily), initially for three weeks. Samples were taken from pustules, from adjacent apparently uninvolved skin, and from the nares. These were submitted for bacterial culture and sensitivity testing. The dogs were re-examined after three weeks treatment and samples for bacteriology were taken from the nares, from any pustules that were present or from skin in the area that was previously affected; the treatment was extended if necessary. Seventy-one per cent of the dogs given lincomycin hydrochloride responded within three weeks compared with 81 per cent of the dogs treated with clindamycin hydrochloride. The overall response rates, including those given longer courses of treatment were 93 per cent for those treated with lincomycin hydrochloride and 94 per cent for those treated with clindamycin hydrochloride, and there was no statistically significant difference between the groups either after three weeks treatment or after extended treatment. The microbiological results demonstrated that Staphylococcus intermedius was present on the skin adjacent to pustules and suggested that the nasal carriage of S intermedius was a result of cutaneous colonisation. PMID- 8488641 TI - Hypereosinophilic syndrome in a cat. PMID- 8488642 TI - Identification of Cheyletiella eggs in dog faeces. PMID- 8488643 TI - Steroid responsive meningitis in three boxer dogs. PMID- 8488644 TI - An unexpected bacterial flora in the proximal small intestine of normal cats. PMID- 8488645 TI - Oiled birds from Shetland, January 1993. PMID- 8488646 TI - Porcine proliferative enteropathy. PMID- 8488647 TI - OVS survey refutes claims of high veterinary fees. PMID- 8488648 TI - Leporine dysautonomia: further evidence that hares suffer from grass sickness. AB - The recently described dysautonomia of hares has many similarities to equine grass sickness, particularly when the autonomic ganglia of affected hares and horses are compared by light microscopy. This study shows that the ultrastructural findings are also similar, with a loss of ribosomes from the rough endoplasmic reticulum and distension of its cisternae; the Golgi apparatus is not recognisable in affected neurons. Membranous stacks were identified in autonomic neurons of affected hares, a feature not characteristic of equine grass sickness but often found in feline dysautonomia. Staining with wheat germ agglutinin, a lectin recognising Golgi membranes, showed a lack of reactivity in affected neurons again suggesting a lack of a normal Golgi apparatus. PMID- 8488649 TI - Xylazine or medetomidine premedication before propofol anaesthesia. AB - The duration of action and cardiopulmonary effects of propofol (6.55 mg/kg intravenously), xylazine (0.8 mg/kg intramuscularly), medetomidine (30 micrograms/kg intramuscularly), xylazine plus propofol (3 mg/kg intravenously) and medetomidine plus propofol (3 mg/kg intravenously) were compared in dogs. A cannula inserted into a raised carotid artery before the drugs were given allowed the continuous recording of blood pressure and heart rate and the measurement of arterial pH, PCO2, PO2, bicarbonate and base balance. Xylazine and medetomidine premedication prolonged propofol anaesthesia in dogs. Propofol alone reduced blood pressure and transiently raised heart rate. The apnoea and hypoxaemia induced by propofol alone also occurred in the premedicated groups with hypoxaemia being most evident in the medetomidine/propofol group. Bradycardia was a common feature in all the dogs given xylazine or medetomidine, but hypertension was consistently recorded in all the dogs given medetomidine. PMID- 8488650 TI - Microsporum canis infection in sheep. PMID- 8488651 TI - Chlamydia psittaci infection in sheep in Northern Ireland. PMID- 8488652 TI - Dirty cattle. PMID- 8488653 TI - Epileptiform seizure in ewes associated with sheep scab mite infestation. PMID- 8488654 TI - Future of veterinary education. PMID- 8488655 TI - Canine leishmaniasis. PMID- 8488656 TI - Casualty slaughter. PMID- 8488657 TI - Report backs central meat hygiene agency. PMID- 8488658 TI - Experimental transmission of BSE and scrapie to the common marmoset. AB - Two young male common marmosets (Callithrix jacchus) were injected intracerebrally and intraperitoneally with a crude brain homogenate prepared from a cow with bovine spongiform encephalopathy (BSE). Two other marmosets were similarly injected with brain homogenate from a sheep with natural scrapie. The two animals injected with scrapie material developed neurological signs 38 and 42 months after injection and the two animals injected with BSE material developed neurological signs after 46 and 47 months. Post mortem examination of the brains revealed spongiform encephalopathy especially in the basal nuclei and diencephalon of all the animals and, in addition, involvement of the cerebral cortex of the marmosets injected with scrapie material. The experiment extends the host range of experimental BSE to include a primate species. PMID- 8488659 TI - Influence of feeding patterns on the artificial infection of laying hens with Salmonella enteritidis phage type 4. AB - Salmonella enteritidis phage type 4 was recovered significantly more frequently from the crops of birds which had been denied food for 24 hours than from birds allowed food ad libitum. There was, however, no difference in its isolation rate from tissues. Within one hour of infection, S enteritidis could be recovered from a variety of tissues, including the oviduct, of a small proportion of the infected birds. PMID- 8488660 TI - Treatment of ovine toxoplasmosis with a combination of sulphamezathine and pyrimethamine. AB - Experimentally induced toxoplasmosis in pregnant ewes was treated with a combination of sulphamezathine and pyrimethamine. Fifteen untreated ewes gave birth to 14 live and six dead lambs whereas all the 15 lambs born to the 12 treated ewes were viable. The placental lesions were less severe, the gestation period was longer and the precolostral antibody titres to Toxoplasma gondii were lower, all significantly, for the lambs born to the treated ewes. PMID- 8488661 TI - Systemic aspergillosis in a dog. AB - Systemic aspergillosis was diagnosed in a two-and-a-half-year-old spayed German shepherd dog which had suffered an acute attack of paralysis of the pelvic limbs. The neurological deficits were attributed to the destruction of the seventh vertebral body and the intervertebral disc, with protrusion of necrotic material into the vertebral canal and compression of the spinal cord at this level. Microscopically, fungal invasion and destruction of the body of T-7 was observed and Aspergillus species were identified. Fungal granulomas were also found in the liver, lung, spleen and mesenteric lymph nodes. PMID- 8488662 TI - Congenital pure red blood cell aplasia (Diamond-Blackfan anaemia) in a dog. PMID- 8488663 TI - Efficacy of moxidectin against an ivermectin-resistant strain of Ostertagia circumcincta in young sheep. PMID- 8488664 TI - Bovine deaths associated with ammoniated straw. PMID- 8488665 TI - Encephalomalacia in first-week chicks. PMID- 8488666 TI - Bovine embryo transfer. PMID- 8488667 TI - Infected feline papilla. PMID- 8488668 TI - Magnetic resonance imaging in the diagnosis of degenerative lumbosacral stenosis in four dogs. AB - Magnetic resonance imaging was used to diagnose degenerative lumbosacral stenosis in four dogs that had physical and neurologic signs consistent with a cauda equina lesion. Nerve root displacement by protruding disc material and loss of epidural fat were identified. In all dogs, the diagnosis was confirmed by dorsal laminectomy of the lumbosacral area. PMID- 8488669 TI - Internal skeletal fixation using a Kirschner apparatus for stabilization of fracture/luxations of the lumbosacral joint in six dogs. A modification of the transilial pin technique. AB - A technique using a modification of the transilial pin technique for stabilization of fracture/luxations of the lumbosacral joint was performed in six dogs. This technique used an internal skeletal fixator composed of two transilial pins secured with two double fixator clamps. Collapse (shortening) of the seventh lumbar vertebra (L7) was observed in five dogs without compromise of the vertebral canal. Kirschner wires placed across the articular facets as supplemental fixation devices migrated to the subcutaneous tissues in two dogs and were easily removed. Migration of the internal fixators was not observed during healing; vertebral canal dimensions were maintained in all cases, and the internal fixators were not removed after resolution of fracture healing. All fractures were healed within 6 to 12 weeks of surgery without evidence of pain, neurologic impairment, or long-term complications. PMID- 8488670 TI - Vascular and morphologic changes in canine femora after uncemented hip arthroplasty. AB - The effects on femoral remodeling of medullary reaming and insertion of a porous endoprosthesis in uncemented hip arthroplasty (UHA) were measured. A unilateral hip hemiarthroplasty (HA) was performed in 12 dogs, with six dogs receiving full sized and six dogs receiving undersized femoral endoprostheses. A prosthetic head and neck, or acetabular cup, was not implanted. A control group of six dogs underwent femoral head and neck excision (FHNE) only. All dogs were killed 4 weeks after the surgical procedure. Porosity, vascularity, and bone formation were quantified in each femur of the dogs that had been operated on and in each femur of two unoperated dogs. Full-sized did not differ from undersized HA bones in vascularity, porosity, or bone formation. Femurs in which hemiarthroplasties had been performed (full-sized and undersized) had a three-fold increase in porosity, vascularity, and bone formation compared to the contralateral and the FHNE femurs. Changes in porosity and vascularity were greatest (p < .05) at the metaphyseal level and in the medial and caudal quadrants. There was a strong correlation (R2 0.77 to 0.93, and p = .0001) between the increase in porosity and vascularity. These results support the hypothesis that medullary reaming followed by uncemented prosthetic stem implantation contribute to remodeling of the proximal portion of the femur after UHA. PMID- 8488671 TI - Bacterial isolates from blood cultures of dogs undergoing dentistry. AB - Bacteria in blood cultures in 30 dogs undergoing high-speed dental scaling and tooth extraction were examined. One or more positive blood cultures were identified in 9 of 30 (30%) dogs. Pasteurella spp. were most frequently (5 dogs) isolated and were sensitive to ampicillin, penicillin, cephalothin, chloramphenicol, tetracycline, amoxicillin with clavulanic acid, and sulfamethoxazole with trimethoprim. Two groups of 15 dogs each, anesthetized or sedated but not undergoing dental procedures, served as non-dentistry controls. There were no significant (p < .05) differences between the number of positive cultures in dentistry and non-dentistry groups. In healthy dogs undergoing high speed dental scaling and tooth extraction, the occurrence of bacteria in blood cultures was much lower than previously reported. The clinical significance of positive blood cultures was uncertain. PMID- 8488672 TI - The effect of hyperbaric oxygen treatment on a compromised axial pattern flap in the cat. AB - A pedicle skin flap based on the caudal superficial epigastric artery was created in 12 cats. The artery was ligated and the vein left intact. Six cats were treated with hyperbaric oxygen at 2 atm absolute for 90 minutes daily for 14 days, starting the day after surgery. Skin flap color was significantly better in the treated cats on days 1, 2, and 3. The amount of exudate was significantly less in the treated cats on day 3. There was no difference in the amount of swelling between treated and nontreated control cats. Although five of six of the treated cats had 100% skin flap survival, there was no significant difference in total flap survival between treated and nontreated control cats. PMID- 8488673 TI - Evaluation of an omental pedicle extension technique in the dog. AB - A two-step omental pedicle extension technique was performed on 10 dogs. Step 1 of the pedicle extension involved release of the dorsal leaf of the omentum from its pancreatic attachment, whereas step 2 consisted of an inverse L-shaped incision to double the length of the pedicle. The pedicle dimensions were measured and the distance reached when extended toward the hind limb, forelimb, and the muzzle recorded after each stage of the procedure. The vascular patency of the pedicle was determined by intravenous injection of fluorescein dye after the second stage of omental extension. Mean pedicle lengths were 44.5 cm with the first stage of extension and 82.0 cm after full extension. The mean width at the caudal extent of the pedicles after dorsal and full extension was 30.4 cm and 17.2 cm, respectively. Eight of the 10 pedicles were patent after full extension. The fully extended omental pedicles reached and, in most cases, extended beyond the distal extremities and the muzzle. The findings in this study suggest that the canine omentum can be extended to any part of the body without being detached from its vascular supply. PMID- 8488674 TI - A retrospective study of inguinal hernia in 35 dogs. AB - Inguinal hernia was associated with trauma in five dogs and was considered nontraumatic in 30 dogs. There were 11 males, 13 intact females, and six spayed females with nontraumatic inguinal hernia. Six dogs had bilateral hernias. Five dogs were younger than 4 months at the time of diagnosis. In 11 older dogs with nontraumatic inguinal hernia, the hernias were identified less than 7 days before surgical repair; in 14 older dogs, the hernias had been recognized for 1 to 60 months. Clinical signs in dogs without small intestinal incarceration were usually limited to a visible or palpable mass without pain or systemic illness. Herniorrhaphy approaches included inguinal, midline with contralateral ring evaluation, and celiotomy with or without inguinal exposure. Fat and omentum were the most common hernial contents. Small intestine was within the hernias of 12 dogs. Six dogs had nonviable small intestine. Postoperative complications included two incisional infections, one incisional dehiscence, two cases of peritonitis and sepsis associated with bowel leakage after intestinal resection and anastomosis, and one hernia recurrence. The overall prevalence of postoperative complications was 17%, and the mortality rate was 3%. Vomiting for 2 to 6 days was predictive of nonviable small intestine. Dogs younger than 2 years were at 11 times greater risk for nonviable small intestine than dogs older than 2 years. Four of five dogs with nontraumatic inguinal hernia and nonviable small intestine were intact males, whereas none of 13 intact females were affected. Only one of 14 dogs with longstanding hernias had nonviable small intestine. PMID- 8488675 TI - Magnetic motor evoked potentials for assessing spinal cord integrity in dogs with intervertebral disc disease. AB - Magnetically elicited transcranial motor evoked potentials (MEPs) were studied in 37 dogs with type 1 intervertebral disc (IVD) disease. The waveforms were recorded from both cranial tibial muscles before and after surgery. The latencies and amplitudes obtained were compared to those of a control population (n = 14). MEPs were recordable in all dogs with mild or no neurologic deficits, but they were recordable in only 50% of ambulatory dogs that were severely ataxic. MEPs could not be elicited from nonambulatory dogs. There was a significant attenuation of the amplitudes in all clinical cases, even if the dogs demonstrated back pain alone. Significantly prolonged latencies were associated with neurologic deficits. MEPs were not good predictors of neurologic recovery. The responses obtained from the side where the disc material was found were not different from those recorded from the opposite side. MEPs were very sensitive to lesions of the spinal cord, as indicated by the significant changes in the waves in patients with mild or no neurologic deficits and in the loss of response in dogs that still demonstrated purposeful movement. Neurologic exams provided more accurate diagnoses and prognoses than did MEPs in dogs with IVD disease. PMID- 8488676 TI - Partial arytenoidectomy in the horse using an extralaryngeal approach. AB - An extralaryngeal approach to partial arytenoidectomy in the horse was developed by in vitro experiments on isolated larynges and then on intact equine cadavers. The goals of the approach were to preserve the laryngeal mucosa, eliminate the need for a laryngotomy or tracheotomy, and minimize postoperative complications. The new approach was evaluated in seven horses with normal upper respiratory tracts. Left laryngeal hemiplegia was surgically created, and, after a 30-day convalescence, left partial arytenoidectomy was performed using an extralaryngeal approach. The left-to-right hemilaryngeal ratio was calculated before and after left recurrent laryngeal neurectomy and 60 days after partial arytenoidectomy. Left partial arytenoidectomy was successfully completed in all horses without performing a laryngotomy or tracheotomy. Preservation of the laryngeal mucosa (6/7 horses) and apparent stabilization of the adjacent soft tissue (6/7 horses) was achieved. In one horse, a 1-cm laryngeal mucosal tear healed without complication, and in another some collapse of adjacent soft tissue occurred when a retention suture failed. The mean left-to-right hemilaryngeal ratio was significantly increased compared to horses with left laryngeal hemiplegia, but it remained significantly less than the pre-recurrent laryngeal neurectomy ratio (p < .05). Coughing, aspiration, and airway narrowing were not observed. Partial arytenoidectomy could be reliably performed through an extralaryngeal approach in horses with a normal underlying arytenoid cartilage with preservation of the laryngeal mucosa. PMID- 8488677 TI - Incarceration of the small intestine in the epiploic foramen. Report of 19 cases (1983-1992). AB - The medical records of 19 horses referred for colic and subsequently found (18 confirmed, 1 suspected) to have small intestinal incarceration through the epiploic foramen were reviewed. These horses were of various ages and breeds; they had clinical signs of colic for an average duration of 13.5 hours before examination. Seventeen horses had nasogastric reflux, and 15 had palpable small intestinal distention. Three horses were killed during surgery because of severe intestinal damage. Of the remaining 16 horses, 13 required intestinal resection and anastomosis. The length of incarcerated small intestine varied from 8 cm to 17.6 m. The ileum was involved in 12 cases. In one horse, the mesoduodenum was disrupted before surgery, causing intra-abdominal bleeding; incarceration of bowel was not found during surgery. The short-term (1 month) survival rate was 74% (14 of 19 cases), and the long-term survival rate was 63% (12 of 19 cases). The follow-up period was 3 months to 45 months (mean 17.2 +/- 7.2 months). PMID- 8488678 TI - Rectal and colonic injury in the llama. Anatomic considerations and surgical management in four llamas. AB - Transrectal palpation in llamas can result in iatrogenic rectal and colonic injury. The purpose of this report is to define the caudal extent of the peritoneal cavity in llamas and to describe the surgical management of rectal or colonic injuries in four llamas. Measurements were made of six adult llamas during necropsy. The mean distance from the peritoneal reflection to the anus was 3.9 +/- 0.1 cm (3.4-4.3 cm). Four llamas were examined for rectal or colonic perforations. One laceration was of partial thickness and three lacerations were of full thickness. Two of the defects were repaired by a transanal approach and two by celiotomy to facilitate removal of fecal debris and abdominal lavage. Successful repair of the rectal or colonic tears was achieved in all four llamas. Wound infection and incisional hernia occurred in both llamas that underwent celiotomy. Two llamas died 3 and 18 months later, and two llamas have survived 2 years. Rectal tears in llamas are accompanied by a high risk of peritoneal contamination, and primary closure is recommended. If fecal contamination of the abdomen has occurred, celiotomy is indicated to allow mechanical removal of fecal debris and peritoneal lavage. PMID- 8488679 TI - Thiamylal-sparing effect of midazolam for canine endotracheal intubation. A clinical study of 118 dogs. AB - One hundred eighteen dogs were studied at three veterinary teaching hospitals after the administration of midazolam (0.1 mg/kg, intravenously [IV]) or a placebo. Midazolam and placebo treatments were randomized and blinded to the investigators. The dose of thiamylal required for tracheal intubation 3 to 5 minutes after midazolam or placebo was calculated. The dose of thiamylal at the three hospitals was 10.6, 9.8, and 10.1 mg/kg i.v. after midazolam, and 12.1, 11.2, and 11.6 mg/kg i.v. after placebo. Pooled data from the three hospitals yielded a significant (p < .001) decrease in mean IV thiamylal dose after midazolam (10.2 mg/kg) compared with placebo (11.6 mg/kg). Overall, there was a 12% decrease in the dose of thiamylal required for tracheal intubation after midazolam compared to that after the placebo. The thiamylal dose was significantly (p < .001) decreased after midazolam compared with placebo for dogs weighing more than 15 kg but not for dogs weighing less than 15 kg. PMID- 8488680 TI - Closed-circuit liquid injection isoflurane anesthesia in the horse. AB - Six horses were administered isoflurane anesthesia by liquid injection into a closed breathing circuit according to the square root of time model. The unit dose (UD) was calculated using Lowe's formula to provide an end-tidal concentration of 1.3%, or the minimum alveolar concentration of isoflurane. The mean UD was 4.2 +/- 0.2 mL. The mean end-tidal isoflurane concentration (ETiso) for each interval after injection, and the peak and minimum concentrations for each injection interval, did not change beginning with the second injection, indicating that the square root of time model accurately predicted isoflurane uptake in the horse. Mean ETiso measured for the interval after the first injection was 0.68 +/- 0.06%, which was significantly (p < .05) lower than the mean concentration after all subsequent injections (1.1 +/- 0.1%). Mean peak end tidal concentration was 1.1 +/- 0.25% after the first injection and 1.7 +/- 0.26% for all other injections. Mean minimum end-tidal concentration was 0.77 +/- 0.13% for all injection periods. This model proved to be an acceptable technique for administration of isoflurane anesthesia to horses. PMID- 8488681 TI - Pulsus alternans during halothane anesthesia in a dog. AB - An adult dog with pyloric obstruction was anesthetized with thiamylal and halothane for surgical revision. When an ECG was attached, the QRS-complex rate was noted to differ dramatically from the peripheral pulse rate. A dorsal pedal arterial catheter was introduced, and direct arterial pressure measurements revealed a blood pressure waveform that alternated in amplitude. Blood pressure and ECG traces were recorded, and the condition was diagnosed as pulsus alternans. The inhalation anesthetic was changed to isoflurane, and the condition was resolved. PMID- 8488682 TI - Radiofrequency catheter ablation for recurrent ventricular tachycardia. AB - Since 1989, six patients have presented to the Charleston Area Medical Center (CAMC) with ventricular tachycardia and no underlying structural heart disease. Three patients were managed with antiarrhythmic medications, and three others underwent a successful catheter ablation procedure. This article describes the case of one of these three patients who underwent catheter ablation. PMID- 8488683 TI - Choroidal metastasis from primary mucinous cystadenocarcinoma of the ovary. AB - Central nervous system metastases are uncommon in epithelial carcinoma of the ovary; and metastases to the eye are even more rare. This article describes what is believed to be only the third case reported of epithelial carcinoma of the ovary metastatic to the eye. PMID- 8488684 TI - A different perspective on obstetrical data. PMID- 8488685 TI - [Comparison of two long-acting theophylline preparations in daily evening administration]. AB - The therapeutic value of a sustained-release theophylline preparation (Theospirex retard 300 mg) with administration of the daily dose once a day in the evening compared to the 2 x 1 dosage usual was investigated in 19 patients suffering from asthma symptoms manifested mainly at night. In this open randomized clinical trial, a sustained-release theophylline preparation (400 mg) which had already been used for administration once a day in the evening served as reference preparation. The single dose in the evening for both preparations was 600 mg pure theophylline. Target parameters were the level of theophylline in the blood, the pulmonary function, symptoms of asthma, and the tolerance of the two sustained release drugs. The theophylline serum levels after 13 respectively 22 hours were 12.44 and 6.98 micrograms/ml for the reference drug and 11.72 and 7.11 micrograms/ml for Theospirex retard. Equivalence of the two drugs was shown in the parameters pulmonary function, symptoms of asthma and tolerance. This study shows that 300 mg Theospirex retard film-coated tablets are suitable for a single administration of the entire daily dose in the evening. PMID- 8488686 TI - [Factor XII (Hageman factor) deficiency: a risk factor for development of thromboembolism. Incidence of factor XII deficiency in patients after recurrent venous or arterial thromboembolism and myocardial infarction]. AB - 103 patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (F XII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with F XII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined F XII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in F XII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of F XII deficiency was significantly higher (20%, p < 0.003). In 67% of the patients with F XII deficiency a positive family history of thrombosis could be established. In contrast, only 32% (p = 0.043) of all venous and 28% (p = 0.019) of all arterial thrombosis patients had a positive family history. We believe that reduced levels of F XII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of F XII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction. PMID- 8488687 TI - [Animals--humans, the physician and ethics]. AB - Ethics and humanitarianism are indivisible. They have to refer to the entire animated and inanimate environment likewise. This has moral as well as essential ecological consequences which are of special actuality at present, with mankind being on the verge of total ecological self-destruction. Key-word: eco-ethics. The worship of the Golden Calf by name of economic growth has to be replaced at last by an acceptance of "shrinking into recovery". Unfortunately, human cruelty is not to be confined to the historical past of the Third Reich, but becomes evident continuously before our very eyes. To shut one's eyes to it is a tendency as widespread as the habit of averting one's eyes from avoidable man-made suffering of animals. We need better education and enlightenment (in the sense of resistance at the very beginning), better control and better execution of better regulations. The health professions, together with educational, ecclesiastical and military professions are called upon to direct attention to this aspect of moral hygiene. PMID- 8488688 TI - [Gender-specific attitude and behavior in dealing with AIDS. Summary of important results]. PMID- 8488689 TI - [Comment on A. Hecht: causality and illness]. PMID- 8488690 TI - [Sense and possibilities of prevention in advanced age: psychosocial aspects]. AB - Cardiovascular diseases have multifactorial causes, as has been shown, and as has been demonstrated via an interactional model. These multifactorial causes must be counteracted by means of multidimensional preventive or rehabilitation measures. Intervention in cardiovascular patients requires interdisciplinary cooperation. Studies conducted so far on rehabilitation of cardiovascular patients have rarely included persons over 60 years of age. This may be explained in part by a poor image of elderly people that exists in the minds of many, discouraging intervention as hardly promising and hence useless. However, persons of an advanced age in particular stand greatly in need of being factually informed at an early date by the physician; such information has a significant influence on the way they can experience and cope with the disease. They must be placed in a position to realise the existing possibilities and limitations to influence their status by means of their attitude, and to look to the future. Successful (secondary) preventive care of elderly persons must also include physical training (kinesitherapy) and psychological aspects when changing dietary habits. On the whole, we are still in need of more research on the problem of possible interventions in cardiovascular patients in general and aged patients in particular. The results of psychological fundamental research in gerontology and intervention supply only few pointers to combatting cardiovascular disease in the elderly. It is however emphasised that psychological measures can merely supplement the medical ones, such supplementation having become so important by now that one should practically not do without it any longer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488691 TI - [Therapy of Wegener's granulomatosis. Experiences with conventional and stage adjusted treatment in 111 patients over 24 years]. AB - Treatment and outcome of 111 patients who fell ill with Wegener's granulomatosis (WG) between 1966 and 1990 were analysed retrospectively. The mean observation time after diagnosis had been 47 (1-288) months. At the time of diagnosis 37 patients suffered from locoregional symptoms only, whereas the disease was generalised in 74 patients. Two regimes of treatment were differentiated: "conventional" treatment, i.e. daily application of cyclophosphamide/prednisolone (FAUCI scheme) or azathioprine/prednisolone or prednisolone alone, and "stage adapted" treatment, characterised by change of different treatments (e.g. cyclophosphamide pulse therapy, cotrimoxazole) according to the extent and activity of disease. In patients who received stage-adapted treatment, relapses occurred significantly more frequently than in conventionally treated patients. On the other hand, lethal outcome was much more frequent in conventionally treated patients. PMID- 8488692 TI - [Gestosis, thrombophilia and pulmonary embolism in a primipara with twin pregnancy]. AB - This is a case report on a course of gemini-pregnancy complicated by gestosis, recurrent submassive pulmonary embolism and discordant growth of the hypotrophic twins. It is concluded from this report that: 1. the AT-III-deficiency in gestosis can be caused by loss and consumption; 2. due to decrease below a critical AT-III-level the coagulation-fibrinolysis system tends to decompensate, reflected in a disseminated intravascular coagulation and/or a pulmonary embolism. The tendency consists particularly in immobilisation and stasis; 3. the daily determination of AT III, better of TAT-complex and D-dimer, the daily clinical examination regarding signs of thrombosis and in cases of heparinization the measurement of PTT several times daily, are necessary to avoid or recognise disorders, of the coagulation-fibrinolysis-system at an early stage. 4. The increased consumption in coagulation systems can be avoided by AT-III substitution and correct heparinisation. 5. In cases of risk of pulmonary embolisation in pregnancy a cava filter should be temporarily implanted. The filter must be changed every 3 days, if it is required for a longer period. 6. In high-risk pregnancy the check for factors of thrombophilia is a basic diagnostic procedure. PMID- 8488693 TI - [Osteomalacia caused by malabsorption]. AB - Reports on sickness osteomalacia are relatively rare in Europe. Distinction from other painful illnesses of the locomotor system is difficult. A case of osteomalacia has been reported which was caused by a primarily biliary cirrhosis of the liver as well as by chronic cholecystitis and pancreatitis. PMID- 8488694 TI - [Autogenic training in hypertensive dysregulation after aortocoronary venous bypass operation of coronary heart disease]. AB - The authors report on the influence of autogenous training on blood pressure at rest and under stress conditions in patients with coronary heart disease following coronary bypass operation. We investigated the influence of autogenous training on the microcirculation and the left ventricular ejection fraction (LVEF) as well. The results showed a significant decrease in blood pressure at rest and also an increase of muscle circulation F and of LVEF. PMID- 8488695 TI - [General practice-oriented curriculum of the 19th century]. AB - Clinical teaching, partly based on the examination and treatment of outpatients, became more and more common at the universities of the end of the 18th century, thus prompting the setting up of so-called "teaching hospitals" forming part of the university concerned and specialising in the disciplines of internal medicine, surgery and obstetrics. This phase of practice-oriented teaching progressed only slowly because of locally different basic conditions and activities. Occasionally it took decades help of communal and private institutions when setting up such teaching facilities. This development is explained taking the University of Halle in the early 19th century as an example. PMID- 8488696 TI - [Vertigo as the main symptom. Diagnosis and therapy from the neurologic viewpoint]. AB - Vertigo is very often an unspecific symptom. The author differentiates between vestibular or systematic vertigo and non-vestibular or unsystematic vertigo. The diseases of the central vestibular system are described. Not only the special diagnostic methods (e.g. electronystagmography) but also the anamnesis and simple clinical investigation are presented. The overview includes drug therapy and physical therapy of vertigo from a neurological point of view. PMID- 8488697 TI - Vaccines and the military. PMID- 8488698 TI - Space flight and the immune system. AB - Depression of lymphocyte response to mitogens in cosmonauts after space flight was reported for the first time in the early 1970s by Soviet immunologists. Today we know that depression of lymphocyte function affects at least 50% of space crew members. Investigations on the ground on subjects undergoing physical and psychological stress indicate that stress is a major factor in immune depression of astronauts. This is despite the fact that weightlessness per se has a strong inhibitory effect on lymphocyte activation in vitro. Although the changes observed never harmed the health of astronauts, immunological changes must be seriously investigated and understood in view of long-duration flight on space stations in an Earth orbit, to other planets such as Mars and to the Moon. PMID- 8488699 TI - Mechanisms of immune failure in burn injury. AB - The burden on military medical services in handling burn casualties is daunting as all physiological systems become affected. Severe burns in a battlefield setting have a very low salvage rate, to a great degree because of the immune failure which invariably develops. Evaluations of responses of lymphocytes taken from burn patients over several weeks following the burn (> 30% total burn surface area), have revealed that the immune failure which follows thermal injury involves T-cell activation events. Interleukin 2, which is normally produced by activated T lymphocytes, is very poorly produced by cells cultivated in vitro taken from non-surviving patients, whereas some production continues, although at below normal levels, in patients who ultimately survive their injury. IL2 exogenously added to lymphocyte cultures enhances the proliferation of cells from surviving patients but gives no such help to cells from non-survivors. The TAC portion of the IL2 receptor (IL2R alpha), expressed on the T-cell surface, appears to be responsible for this difference, as the number of lymphocytes able to express IL2R alpha falls post-burn. A lipid protein complex (LPC) produced in skin by burning has been shown to inhibit the immune response in vivo and the growth of IL2-dependent lymphocytes in culture. Cerium nitrate, applied topically to the burn patient, is thought to fix the LPC in the burn eschar and prevent its entry into the circulation. In a study of ten patients, bathed in cerium nitrate, some T-lymphocyte activities were found to be in the normal range rather than suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488700 TI - Clinical types of HBsAg-positive hepatitis. AB - Hepatitis B is a parenterally and sexually transmitted disease of global importance. It associates with hepatitis D in a consistent proportion of cases. The disease most frequently runs a subclinical and anicteric course, with a significant number of cases that become chronic. Chronic hepatitis may progress to cirrhosis or cancer. The strategies by which hepatitis B and hepatitis D can be diminished and eventually eliminated are: immunization, measures to prevent exposure to infective blood or blood derivatives and education (in particular awareness that hepatitis B is a sexually transmitted disease). PMID- 8488701 TI - Viral hepatitis in the US Air Force, 1980-1989. AB - Viral hepatitis and its acute and chronic complications continue to pose significant threats to the readiness of military personnel. Knowledge about the specific viral agents and their routes of transmission are important in developing prevention strategies. A recent analysis of hepatitis in the US Navy for the period 1975-1984 is reviewed. In order to better characterize the risk of viral hepatitis among US Air Force personnel, a comprehensive review of inpatient and quarters data for hepatitis A, B and 'non-A, non-B' were reviewed from Air Force medical treatment facilities worldwide for the period 1980-1989. Following a discussion of the study methodology, preliminary data and hepatitis type specific demographic risk variables are discussed. Preliminary results from a hepatitis serosurvey (A, B and C antibody with use of a supplemental validating assay) of the subset of the study cohort who are currently on active duty are briefly reviewed. PMID- 8488702 TI - Vaccination against hepatitis B: the Italian strategy. AB - Viral hepatitis B, which is a major health problem worldwide, is endemic in Italy. In response to this, vaccination became compulsory in 1991. Vaccine is administered to neonates and 12-year-old adolescents; in 12 years time, all Italians under the age of 24 will be immune to HBV. PMID- 8488703 TI - HIV infection in the nineties. AB - By the year 2000 a cumulative global total of 30-40 million men, women and children are projected to have been infected with HIV. This will represent a three to four times increase of the present total. Currently, it is estimated that about 5000 persons are newly infected daily. Worldwide, the predominant and increasing mode of transmission is by heterosexual intercourse. Therefore, the number of infected women will equal that of men. Consequently, more infants will be infected by their mothers and more infants will be orphaned as their parents die of AIDS. By the end of the 1990s, over one million adult AIDS cases and deaths per year are expected, most of them in developing countries. Although the majority of HIV infections are currently occurring in sub-Saharan Africa, the annual number of HIV infections in Asia is projected to exceed that in Africa during the 1990s. Also, in industrialized countries, the proportion of heterosexual transmission is increasing, and AIDS is becoming one of the predominant causes of death in young men and women. In spite of promising scientific progress, vaccines and therapeutic drugs are not expected to have any major impact on the global development of the pandemic during the 1990s. WHO is promoting behavioural changes, condom use and control of other sexually transmitted diseases as the most important preventive measures. PMID- 8488704 TI - AIDS/HIV in the US military. AB - HIV infection (AIDS) burst upon the scene a decade ago. Because it is a sexually transmitted disease that infects blood and kills its victim, it is military relevant and will impact on all aspects of the military. The US Army Medical Research and Development Command as 'Lead Agent for Infectious Disease Research' in the Department of Defense has developed a comprehensive approach to address military concerns: surveillance of infection rates (intelligence) around the world and in the military; behavioural research to develop more effective means of education to change behaviour; and biological research to develop a quick and easy field test, and a vaccine or drug to prevent the disease from occurring despite exposure. Its success will influence the success of the Army in the future. PMID- 8488705 TI - Estimates of human immunodeficiency virus (HIV) incidence and trends in the US Air Force. AB - The results of HIV screening between early 1986 and February 1991 in the United States Air Force are presented. In this period, two total-force screenings were conducted. HIV incidence estimates are presented by age, ethnicity/race, sex and occupational category. PMID- 8488706 TI - Silent HIV infection. AB - The period of latency between infection by the human immunodeficiency virus type 1 (HIV-1) and the production of specific antibodies to viral antigens may be prolonged and, occasionally, may last for years. This condition of seronegative infection could represent a serious risk of viral transmission from subjects who are unaware of their status. However, whether these individuals are actually infectious, especially through body fluids, has not been clarified. We have performed a prospective study in 65 high-risk individuals seronegative for HIV-1 antibodies for a prolonged period of time. Twelve of them (18%) were shown to be carriers of HIV-1 proviral sequences by the polymerase chain reaction (PCR). The virus was isolated from mitogen-stimulated peripheral blood lymphocytes in five out of ten subjects tested since the first positive PCR. In two of them, virus could also be isolated from cell-free plasma, subsequently they remained seronegative during 10 months of follow-up. These data indicate that delayed seroconversions may be associated with productive infection, suggesting that mechanism(s) other than viral latency may be responsible for the absence of antibody responses to HIV-1 proteins. Furthermore, our findings suggest that prolonged seronegative individuals can transmit HIV infection through their body fluids. PMID- 8488707 TI - HIV variability and perspectives for a vaccine. AB - An overview of efforts to induce neutralizing antibodies in order to develop an effective vaccine against AIDS is presented. The principal Neutralizing Determinant (PND) on the HIV-1 envelope is described. PND variability and the induction of neutralizing antibodies by synthetic peptides representing PND are discussed. The use of a cocktail of different peptides representing the PND sequences of the majority of HIV-1 isolates, as well as the construction of hybrid immunogens containing PND of several viral isolates, could overcome the problems related to PND variability. A different approach based on the possibility of inducing a type of intracellular immunity is also discussed: a cellular clone (F12) obtained in our laboratory from Hut-78 cells infected with supernatant of cultured lymphocytes from an HIV-infected patient, does not release viral particles despite the presence of a full-length HIV-1 provirus. Moreover, F12 cells are fully resistant against superinfection with any HIV-1 or HIV-2 isolates. We are now attempting to reproduce the homologous viral interference by transferring the F12/HIV genome of the clone into HIV-susceptible cells in order to render these cells resistant to HIV infection. PMID- 8488708 TI - Immunological parameters in current and former US Air Force personnel. AB - As part of a comprehensive study of current and former US Air Force personnel, an extensive assessment of the immune system of 497 normal male subjects was conducted in 1987. Cell surface marker studies for CD2 (total T cells), CD4 (helper T cells), CD8 (suppressor T cells), CD25 (activated T cells), CD20 (total B cells), CD14 (monocytes), and HLA-DR positive cell populations were measured. The CD4/CD8 ratio was also calculated. Functional stimulation assays were also performed using phytohemagglutinin (PHA) and a culture of mixed lymphocytes. Assays of natural killer cells with and without interleukin-2 stimulation were done. In addition to the distribution and range of values for each assay, statistical analyses were performed to determine the effect of age, race, percentage body fat, tobacco use and alcohol consumption on each variable. Age and alcohol consumption had significant correlation with suppressed counts and functions on nearly all variables while tobacco use was associated with stimulation of both T-cell numbers and function. These findings highlight the importance of using age-specific ranges of normal values for these tests of immunity and the need to consider life-style factors in the interpretation of the laboratory assessment of immune status. PMID- 8488709 TI - Analysis of disease progression from clinical observations of US Air Force active duty members infected with the human immunodeficiency virus: distribution of AIDS survival time from interval-censored observations. AB - A non-parametric estimator of the AIDS survival time (after developing AIDS) is computed for the AIDS data set from the US Air Force (USAF). Survival times are unobservable. They are censored by the screening mechanism. The Armstrong Laboratory's Epidemiologic Research Division maintains data on over 954 active duty US Air Force (USAF) individuals who tested positive for human immunodeficiency virus (HIV) antibodies. Many have been clinically evaluated seven times since 1986. The HIV-positive individual is classified in seven stages of the disease complex as time progresses. Exact times of transition from one stage to the next are unknown. It is known that transition occurred between two consecutive evaluations. The aim of this study is to analyse distributions of the times that individuals spend in each stage of the HIV disease complex. We will discuss methods used to obtain non-parametric estimators of the distribution of times that individuals spend in stage 6. Finally, it is hoped to model the median time spent in each stage of the disease. This, along with incidence and separation data, will allow the prediction of the impact of HIV disease on USAF individuals and medical care systems. PMID- 8488710 TI - Relating cognitive function to military aviator performance in early HIV infection. AB - There has been controversy about whether cognitive changes occur in early human immunodeficiency virus (HIV) disease. In those studies reporting cognitive changes, these are typically subclinical, and their relationship to daily and/or occupational functioning has not been addressed. The potential effects of changes may vary as a function of occupational demands. This is germane to military performance, where occupational demands cover a wide spectrum of complexity. In particular, such effects are important to consider in the many cognitively demanding specialties associated with military aviation. This paper will explore ways in which possible HIV-related military performance decrements in aviators may be measured empirically. First, studies from Walter Reed Army Medical Center (WRAMC), which have shown cognitive changes in early HIV disease, will be described. This will be followed by a summary of presentations and discussions at a conference in November 1990, entitled 'HIV and Military Performance: Assessment Methodologies' held at WRAMC. The third section of the paper will describe a programme of research, which is developing measures to detect cognitive difficulties in civilian aviators. The application of measures from this research to research on HIV will be discussed. Finally, a research programme being developed to examine the possible impact of HIV-related cognitive changes on military aviator performance will be described. PMID- 8488711 TI - Neuropsychiatric morbidity in early HIV disease: implications for military occupational function. AB - The Military Medical Consortium for Applied Retroviral Research Program's (MMCARR) Behavioral Medicine Human Immunodeficiency Virus (HIV) Research component is conducting a tri-service, comprehensive, and longitudinal research study in military HIV-infected personnel at all stages of infection. Identification of neuropsychiatric and psychosocial outcomes and their determinants will help the military minimize the impact of the HIV epidemic on military readiness and function. Neuropsychiatric and psychosocial findings are among the most common complications seen in early HIV disease and among the most likely to have an adverse impact on military readiness and function. The study has demonstrated that the average HIV-infected service person experiences at least transient military occupational difficulty following notification of HIV status. More than 15% at any given time have levels of clinical or subclinical anxiety or depression that are referrable for mental health intervention. Ten per cent of study subjects have a current major mood disorder and 5% have a psychoactive substance use disorder. Finally, 17% of study subjects have experienced serious suicidal ideation or behaviours at least once since notification of seropositivity. Fortunately, however, data also indicate at least partial effectiveness of current primary, secondary and tertiary preventive efforts. Only about 1% of Air Force HIV-infected persons are discharged for psychiatric reasons prior to eventual medical discharge. Further, a large majority of active-duty patients demonstrate solid military occupational and social performance. Though military HIV neurobehavioural research is still in progress, preliminary data identify social support and pre-HIV psychiatric predisposition as important factors associated with current neuropsychiatric status. PMID- 8488712 TI - Communicable diseases: a major burden of morbidity and mortality. AB - A brief overview of the present situation regarding some of the world's most important diseases is given. Particular mention is made of dengue, yellow fever, malaria and parasitic diseases. Vaccination is concluded to have a major role in combating these diseases. PMID- 8488713 TI - Susceptibility in USAF recruits to vaccine-preventable diseases. AB - Because of increasing incidence of mumps in a cohort of underimmunized young adults and the concern about the impact of this disease on the USAF recruit population, two studies were undertaken. These studies took a retrospective look at mumps in the active duty population, a cost analysis of immunizing all or only susceptible individuals, the actual antibody response in a group of 276 recruits in basic training, the demographic patterns of susceptibility and the types of previous immunization documentation. The conclusions were that the numbers of new mumps cases per year did not justify immunizing all recruits or screening for mumps antibodies and only immunizing known susceptibles. PMID- 8488714 TI - Absence of protective immunity against diphtheria in a large proportion of young adults. AB - The schedule of vaccination recommended worldwide for diphtheria, tetanus and other diseases, provides good immunity during childhood. However, little attention has been paid to effective immunity in adults. We have collected sera from 334 Italian Army recruits and tested them for the presence of protective immunity against diphtheria and tetanus. In vivo neutralization assays were performed on rabbits and mice and values below 1/100 IU ml-1 were considered negative. Of the recruits, 22.9% were negative for diphtheria, while only 5.3% had no protective immunity against tetanus. This finding shows that a large proportion of Italian young adults are susceptible to diphtheria, and this could be dangerous if they travel to sites where this disease is still endemic, or if they come into contact with people coming from such areas. A booster vaccination of young adults against diphtheria should become common practice to avoid this risk. To reduce the side effects which are often associated with diphtheria vaccination in adults, we have developed a vaccine which contains a highly purified, non-toxic mutant of diphtheria toxin. This vaccine is combined with tetanus toxoid and can be routinely used as a booster in adults. PMID- 8488715 TI - Dramatic reduction of meningococcal meningitis among military recruits in Italy after introduction of specific vaccination. AB - Meningococcal meningitis is still a serious infectious disease with a mortality rate that can be as high as 10% even in developed countries. Military recruits are generally a high-risk group for meningococcal disease, with a reported incidence of four to ten times greater than that of the general population. In Italy the results of the National Meningitis Surveillance Programme showed a high attack rate of the disease among recruits in 1985 as well as in 1986, with 92 and 95% of the cases, respectively, caused by serogroup C and thus preventable. These findings led to the authorities' decision to make vaccination against meningococcal disease mandatory for recruits starting from January 1987. After almost 5 years from the introduction of meningococcal vaccination, we here sum up the epidemiological and immunological effects of the vaccination. From the epidemiological point of view we have observed a dramatic reduction of the prevalence of the disease. In 1987, the year in which we had 150,000 unvaccinated and 150,000 vaccinated recruits, the protective efficacy was 91.2%. From the immunological point of view, vaccination is highly effective, as seroconversion against polysaccharide (PS) A and C is 84 and 91%, respectively. The spectrotypic analysis of the sera before and after vaccination shows that the type of response is mainly oligoclonal, like the majority of the responses to PSs, and the antibodies induced by a sole PS are not qualitatively different from the antibodies induced by natural immunization. In addition, the efficacy is not modified by environmental factors like hypoxia, as demonstrated during permanence at 16,174 feet for 20 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488716 TI - Clinical and immunological response to typhoid vaccination with parenteral or oral vaccines in two groups of 30 recruits. AB - The clinical and immunological responses to typhoid vaccination with parenteral and oral vaccines in two groups of 30 adult male subjects were studied. Specific anti-Salmonella typhi cell-mediated immunity and total or specific anti lipopolysaccharide faecal immunoglobulin (Ig) A titres in vaccinated subjects were monitored. Cellular antibacterial activity was significantly increased only in orally vaccinated subjects. Serum arming activity and inhibition experiments suggested an IgA-dependent cellular cytotoxicity in those orally vaccinated. In these subjects, a total and anti-lipopolysaccharide faecal IgA increase was observed lasting up to 8 months after completion of the vaccination schedule. In parenteral vaccinated subjects, an early onset transitory increase of IgM rheumatoid factor was observed. Oral vaccine was well tolerated and free of side effects, whereas 65% of parenterally vaccinated subjects reported side effects such as fever, headache, malaise and local tenderness in the injection site. PMID- 8488717 TI - Studies of safety, infectivity and immunogenicity of a new temperature-sensitive (ts) 51-1 strain of Salmonella typhi as a new live oral typhoid fever vaccine candidate. AB - This report describes the results of a phase 1 study evaluating the safety, infectivity, and immunogenicity of a new live oral Salmonella typhi temperature sensitive (ts) 51-1 typhoid fever vaccine in the human. Three normal male subjects aged 23-32 years received three oral doses of S. typhi ts 51-1, each dose containing 10(9) organisms. Prior to and following immunization each subject was carefully monitored by clinical and laboratory parameters over a 2 week period during which serial specimens of blood and stool were analysed for the presence of the organism. Blood specimens were also obtained for the determination of serum antibody and cell-mediated immune responses and stool filtrates were analysed for the development of coproantibody. The results of these studies indicate that: (1) the vaccine is well tolerated with no clinical or laboratory evidence of adverse reactions; (2) ts 51-1 was detected in only one stool specimen from one volunteer; the organism recovered displayed characteristics of the ts 51-1 vaccine strain; and (3) although no significant humoral or cell-mediated lymphocytotoxic immune responses were detected in the blood, coproantibody was detected in stool specimens from all of the three immunized subjects and IgA-armed ADCC activity was detected in two of three subjects. These studies indicate that S. typhi ts 51-1 may be a suitable strain for the development of an improved oral typhoid fever vaccine. Studies are in progress to determine optimal methods of vaccine delivery preparatory to large phase 2 studies of efficacy. PMID- 8488718 TI - Use of novel adjuvants and delivery systems to improve the humoral and cellular immune response to malaria vaccine candidate antigens. AB - The immune effector mechanisms responsible for the solid protection against malaria, as demonstrated by immunization with radiation-attenuated sporozoites, are poorly understood. An effective malaria vaccine must induce a well orchestrated combination of humoral and cellular immune responses directed against critical parasite antigens/epitopes expressed during different stages of the parasite's complicated life cycle. Currently licensed human vaccine adjuvants, such as alum, may improve antibody production but are poor stimulators of cellular effector mechanisms, while potent cellular stimulants such as Freund's adjuvant are too reactogenic for human use. Over the last 5 years we have systematically evaluated several methods of antigen presentation to include chemical conjugation to bacterial carrier proteins, emulsification in 'Freund's like' preparations, and incorporation into liposomes. This work has resulted in the production of safe, potent vaccine delivery systems capable of targeting multiple antigenic determinants to the host's immune system. Further advances in malaria vaccine development now depend on the identification of appropriate parasite epitopes for inclusion in a multicomponent-multistage vaccine. PMID- 8488719 TI - Cytokines as vaccine adjuvants: interleukin 1 and its synthetic peptide 163-171. AB - The possibility of preventing infectious diseases by employing efficacious vaccine is rapidly growing as a consequence of the new technologies in recombinant DNA and protein chemistry. However, the increasing number of synthetic and recombinant antigens further stresses the role of appropriate adjuvants to ensure maximal vaccine activity and the protection of all vaccinees. Several approaches can be applied to develop safe and effective agents capable of enhancing specific immune responses which can then protect the host from the pathogen. Among others, the direct use as adjuvant of those cytokines which are induced in animals by the classical Freund's adjuvants has recently become a matter of investigation. In particular, interleukin 1 (IL-1) has been shown to possess adjuvant activity for a variety of infectious and tumour antigens. However, the numerous side effects associated with the proinflammatory action of IL-1 represent a serious disadvantage for its use as a vaccine adjuvant. It was therefore of great interest that a nonpeptide contained in the IL-1 beta sequence (residues 163-171 corresponding to the sequence VQGEESNDK) is devoid of all proinflammatory activities but maintains the immunostimulating activity of the whole IL-1 beta. Thus, peptide 163-171 was successfully employed in animals to potentiate the specific immune response against T-helper-dependent cellular antigens, T helper-independent polysaccharidic antigens and recombinant as well as synthetic antigenic preparations derived from human pathogens. Furthermore, IL 1 and peptide 163-171 have been successfully used in tumour vaccines in experimental systems. It can therefore be concluded that peptide 163-171 is potentially a good candidate as vaccine adjuvant for human use. PMID- 8488720 TI - Future approaches to vaccine development: single-dose vaccines using controlled release delivery systems. AB - The development of single-dose vaccines, mainly those administered during childhood, which would effectively protect against certain diseases, would be a very important advance towards better immunization coverage and protection against the respective pathogens. Biodegradable polymeric microspheres which are 'programmed' to deliver the antigen when a boost of the immune response is required, may be a possible way of achieving this goal. PMID- 8488721 TI - The amino terminal sequence of VP60 from rabbit hemorrhagic disease virus supports its putative subgenomic origin. AB - Direct determination of the amino acid sequence of VP60 from rabbit hemorrhagic disease virus is impeded by the presence of a blocked N-terminus. Chemical cleavage of VP60 using cyanogen bromide allowed the identification and purification of two oligopeptides showing identical amino acid composition, one of which had its amino terminus blocked. Automated sequential degradation of the unblocked CNBr- peptide yielded the amino acid sequence EGKARTAPQGEAA. This sequence is identical to the deduced amino acid sequence following the first AUG codon found at position +10 at the 5'-end of the 2.4 kb subgenomic mRNA. These data favor the hypothesis that this viral polypeptide is mainly produced from the subgenomic mRNA and not from the genomic RNA by processing of the putative polyprotein generated from the major open reading frame. PMID- 8488722 TI - Heterogeneity of the woodchuck hepatitis virus genome in a chronically infected woodchuck. AB - The nucleotide sequence of an isolate of woodchuck hepatitis virus (WHV) from the serum of a woodchuck trapped in New York state (WHVNY) was compared with the sequences of previously published isolates. The nucleotide sequence of WHVNY was closest to that of an isolate originating from New Jersey: the two genomes shared a 15 nucleotide in-frame deletion in the region where the presurface and polymerase genes overlap (nucleotides 3260-3274) and differed by 54 point mutations (1.6% of genome). Amino acid differences ranged from 0.4% in the surface gene to 5.7% in the X gene. Three isolates from woodchucks that originated in Pennsylvania and Maryland did not contain the deletion and differed from WHVNY by 102 to 106 point mutations (3.0% to 3.2% of nucleotides). Amino acid changes ranged from 0.5% in the core gene to 5.7% in the X-gene. Thus, WHVNY differed little from previous isolates. Next, the genomes from 102 independent clones of WHVNY were compared to ascertain the extent of sequence variation among WHV genomes in a chronically infected animal. A total of 98 clones had genomes of unit length while 2 clones had genomes shorter than unit length and 2 clones had genomes longer than unit length. The clones not of unit length possessed deletions or inverted duplications of sequence. The rate of mutation in the viral genes was 2.65 mutations per 10,000 nucleotides in the precore domain, 1.27 per 10,000 in the X-gene, 0.98 per 10,000 in the presurface gene, and 3.77 per 10,000 at the 5' end of the core gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488723 TI - Characterization of plasma membrane H(+)-ATPase from salt-tolerant yeast Candida versatilis. AB - Plasma membrane was isolated from the salt-tolerant yeast Candida versatilis and the ATPase in plasma membrane was characterized. The ATPase was a typical H(+) ATPase with similar properties to the Saccharomyces cerevisiae and Zygosaccharomyces rouxii enzymes. It was reacted with antibody (IgG) raised against S. cerevisiae plasma membrane H(+)-ATPase. The ATPase activity was not changed by adding NaCl and KCl to the assay solutions, but was increased by NH4+, especially by ammonium sulfate. In vivo stimulation of ATPase activity was observed by the addition of NaCl into the culture medium, as observed in Z. rouxii. No in vivo activation of H(+)-ATPase by glucose metabolism was observed in C. versatilis cells and the activity was independent of the growth phase, like Z. rouxii and unlike S. cerevisiae cells. PMID- 8488724 TI - Reduced efficiency in the glycosylation of the first sequon of Saccharomyces cerevisiae exoglucanase leads to the synthesis and secretion of a new glycoform of the molecule. AB - In addition to exoglucanases (EXGs) I and II, old cultures of Saccharomyces cerevisiae secreted into the culture medium a new immunologically-related material that exhibited exoglucanase activity. The new exoglucanase (EXGII1/2) was purified from stationary-phase cultures. It turned out to be a glycoprotein whose protein portion was identical to that of the other two isoenzymes in terms of ionic properties, size, amino acid composition and NH2-terminal sequence (25 residues). Disruption of the structural gene encoding EXGs I and II resulted in a strain unable to secrete all three isoenzymes. EXGII1/2 was indistinguishable in terms of molecular weight from the single intermediate detected during the deglycosylation (mediated by endo H) of EXGII by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Thus, the new isoenzyme contains only one of the two slightly elongated mannan inner cores present in enzyme II. Two intermediates were, however, detected when the deglycosylation of EXGII was monitored by ion-exchange chromatography (high-pressure liquid chromatography). Site-directed mutagenesis indicated that the major intermediate, which eluted at about the same position as enzyme II1/2, corresponded to protein molecules carrying the oligosaccharide attached to the Asn of the second sequon, whereas the minor one carried the oligosaccharide in the first potential glycosylation site. Several lines of evidence indicate that EXGII1/2 is a biosynthetic product resulting from an imbalance between the rate of protein synthesis and the glycosylation capabilities of the glycosylation machinery. PMID- 8488725 TI - Nuclear pore complex antigens delineate nuclear envelope dynamics in vegetative and conjugating Saccharomyces cerevisiae. AB - In the yeast Saccharomyces cerevisiae, the nucleus undergoes dramatic shape changes during mitosis and mating. We have studied nuclear envelope dynamics during the processes of mitosis and conjugation using nuclear pore complexes as a marker for the nuclear envelope in wild-type cells and several cell-division cycle (cdc) mutants. Three monoclonal antibodies are described that recognize nuclear pore complex-related antigens in S. cerevisiae. One of these antibodies, RL1, has been extensively characterized by Gerace and colleagues and recognizes nuclear pore complexes in mammalian and amphibian cells. By indirect immunofluorescence of yeast cells, all three antibodies yield a discontinuous nuclear rim stain. All three react with multiple nuclear-enriched proteins in immunoblots, including the nucleoporin protein encoded by the NSP1 gene. When the antibodies were used in immunofluorescence experiments on mating cells, the nuclear pore complex staining pattern proved to be a sensitive indicator of nuclear fusion. Nuclei with closely apposed spindle pole bodies and unfused nuclear envelopes could be readily distinguished. Marked shape changes were observed in nuclei during fusion and segregation of the diploid nucleus into the zygotic bud. In cdc14 and cdc15 mutants that arrest late in mitosis, the elongated nuclear envelope extension that stretches between daughter nuclei during telophase was preserved. In cytokinesis-defective mutants (cdc3, cdc10, cdc11 and cdc12), the elongated nuclear envelope was usually resolved into two daughter nuclei in the absence of cytokinesis. These results indicate that nuclear envelope division is mechanically distinguishable from chromosome segregation, nucleolar segregation and cytokinesis. PMID- 8488726 TI - Role of the gamma component of preprotoxin in expression of the yeast K1 killer phenotype. AB - K1 killer strains of Saccharomyces cerevisiae secrete a polypeptide toxin to which they are themselves immune. The alpha and beta components of toxin comprise residues 45-147 and 234-316 of the 316-residue K1 preprotoxin. The intervening 86 residue segment is called gamma. A 26-residue signal peptide is removed on entry into the endoplasmic reticulum. The Kex2 protease excises the toxin components from the 290-residue glycosylated protoxin in a late Golgi compartment. Expression of a cDNA copy of the preprotoxin gene confers the complete K1 killer phenotype on sensitive cells. We now show that expression of immunity requires the alpha component and the N-terminal 31 residues of gamma. An additional C terminal extension, either eight residues of gamma or three of four unrelated peptides, is also required. Expression of preprotoxin terminating at the alpha C terminus, or lacking the gamma N-terminal half of gamma causes profound but reversible growth inhibition. Inhibition is suppressed in cis by the same 31 residues of gamma required for immunity to exocellular toxin in trans, but not by the presence of beta. Both immunity and growth inhibition are alleviated by insertions in alpha that inactivate toxin. Inhibition is not suppressed by kex2, chc1 or kre1 mutations, by growth at higher pH or temperature, or by normal K1 immunity. Inhibition, therefore, probably does not involve processing of the alpha toxin component at its N-terminus or release from the cell and binding to glucan receptors. Some insertion and substitution mutations in gamma severely reduce toxin secretion without affecting immunity. They are presumed to affect protoxin folding in the endoplasmic reticulum and translocation to the Golgi. PMID- 8488727 TI - Yeast mutants affected in viability upon starvation have a modified phospholipid composition. AB - Selection of mutations, based on the suppression of rvs161 delta defects, was performed. Ten mutants were obtained, ranged amongst four complementation groups, named SUR1, SUR2, SUR3 and SUR4. All sur mutations also suppress a mutation in another gene, RVS167, indicating that all six genes are involved in the same biological pathway. The sur mutant cells have abnormal morphologies in stationary phase, i.e. dumbbell-like in sur1, sur2 or sur3 strains and multi-budded in sur4 strains. Several phenotypic characteristics of the physiological suppressors as well as the rvs161 delta strain itself led us to analyse the phospholipid composition of the mutants. The assays show an overall decrease of the phospholipid amounts and modifications in the relative contents of some phospholipid classes in sur mutant cells. PMID- 8488728 TI - Sequence of a 7.8 kb segment on the left arm of yeast chromosome XI reveals four open reading frames, including the CAP1 gene, an intron-containing gene and a gene encoding a homolog to the mammalian UOG-1 gene. AB - We report here the DNA sequence of a segment of chromosome XI of Saccharomyces cerevisiae extending over 7.8 kb. The segment contains four long open reading frames, YKL150, YKL153, YKL155 and YKL156, YKL155 corresponds to the CAP1 gene. YKL153 contains an intron and shows an extremely biased codon usage suggestive of a highly expressed protein. YKL156 is a homolog to UOG-1, an open reading frame associated with the cDNA clone of the mammalian growth/differentiation factor 1. YKL150 reveals common motifs to both the RNA polymerase II elongation factor of Drosophila melanogaster and to the yeast PPR2 gene product. PMID- 8488729 TI - Sequence of a 4.8 kb fragment of Saccharomyces cerevisiae chromosome II including three essential open reading frames. AB - The nucleotide sequence of a fragment of 4867 base pairs of Saccharomyces cerevisiae chromosome II has been determined. The sequence contains three complete open reading frames. In addition to the already known gene RPB5, coding for a subunit shared by all three DNA directed RNA polymerases, two new open reading frames could be identified. YBR12.03 codes for a protein of 183 amino acids with homology to one of the proteins of the Bacillus subtilis riboflavin biosynthesis operon (RibG). Deletion mutants of YBR12.03 can germinate but stop growing after five to seven cell divisions on YPD. Supplementation with high concentrations of riboflavin does promote growth. YBR12.05 codes for a protein of 386 amino acids with homology to STI1, a stress-inducible protein of S. cerevisiae. Deletion mutants of YBR12.05 are not viable. PMID- 8488730 TI - RPB7, one of two dissociable subunits of yeast RNA polymerase II, is essential for cell viability. AB - The Saccharomyces cerevisiae RNA polymerase II subunit gene RPB7 was isolated and sequenced. RPB7 is a single copy gene whose sequence predicts a 19,000 Dalton protein of 171 amino acids. RPB7 is known to dissociate from RNA polymerase II as an RPB4/RPB7 subcomplex in vitro. RPB7 also appears to interact with RNA polymerase II in a manner dependent upon RPB4, since RNA polymerase II purified from cells lacking RPB4 also lacks RPB7. Previous results have demonstrated that deletion of the RPB4 results in slow growth and cold- and temperature sensitivity. In contrast, deletion of the RPB7 gene revealed that it is essential for cell growth and viability. Loss of both the RPB4 and the RPB7 genes causes lethality. These results suggest that RPB7 contributes to the function of RNA polymerase II in the absence of RPB4 either in a manner independent of its association with the enzyme or by directly binding to the enzyme in a manner independent of its association with RPB4. PMID- 8488731 TI - YMC1, a yeast gene encoding a new putative mitochondrial carrier protein. AB - We have cloned and sequenced a Saccharomyces cerevisiae gene coding for a protein with significant similarities to the mitochondrial carrier family. The gene we termed YMC1 (yeast mitochondrial carrier) is located on chromosome XVI, closely downstream of ARO7 encoding chorismate mutase. PMID- 8488732 TI - [Progress in biology and the treatment of acute promyelocytic leukemia]. AB - Acute promyelocytic leukaemia (APL) is a distinct subtype of acute myeloid leukaemia distinguished by the presence of a balanced chromosomal translocation: t(15; 17). The most characteristic clinical manifestation of this disease is the presence of a haemorrhagic syndrome associated with an abnormal coagulation profile. In the last few years significant progress in the understanding of the biology of this leukaemia and its treatment has been done. In particular, the breakpoint on chromosome 17 has been localized within the retinoic acid receptor alpha locus while the breakpoint on chromosome 15 has been localized within a new gene named PML. In contrast to the other acute myeloid leukaemia subtypes APL shows high response rate to induction monochemotherapy with anthracycline drugs and with all-trans retinoic acid. PMID- 8488733 TI - [The origin of fibrinogen in megakaryocytes and blood platelets]. AB - Fibrinogen is involved in platelet aggregation and clot formation. It is mainly synthesized by hepatocytes. The additional, small pool of this glycoprotein is known to exist in the alpha granules of bone marrow megakaryocytes and blood platelets. Up-date of the origin of fibrinogen in these cells has been discussed. PMID- 8488734 TI - [Comparison of computed tomography results and pathological findings after laparotomy with splenectomy in Hodgkin's disease]. AB - In 69 patients (pts) with Hodgkin's disease (HD) in I-IIIA clinical stage results of abdominopelvic computed tomography (CT) were compared with pathological staging. Concordance (specificity) of CT scan with results of macroscopic evaluation of HD lesions in the abdomen during laparotomy with splenectomy was 83%. Accuracy CT results and microscopic findings was 80%. False positive results of CT were found in 11.6% of patients and false negative in 8.6%. Specificity and sensitivity of CT versus to pathological staging were 84% and 63% respectively. The results presented here confirm, that pathological staging after laparotomy with splenectomy in HD was some advantage in precise prediction of some patients to radiotherapy and planning of irradiated fields. PMID- 8488735 TI - [Long-term (over 10-years) survival in Hodgkin's disease]. AB - 61 patients with Hodgkin's disease, i.e., 40.9% of all HD pts hospitalized in the years 1970-1981 are more than 10 years survivors: 46 are alive and 15 died of underlying disease or its complications. The most important prognostic factor at diagnosis was clinical advancement and the form A or B of HD. Age and sex also influenced survival but to a lesser degree. Patients living in CCR were more likely to have MC histology than those with relapsing disease, who more often showed LD and LP type. Among 5 persons with second neoplasms four disclosed NS type of HD. No statistical differences in clinical prognostic factors were encountered between further alive and those who died after more than 10-yrs. Almost all patients were able to normally continue their familial and professional lives. PMID- 8488736 TI - [Use of microtest in gel for compatibility in serological testing before transfusion]. AB - A gel technique for the detection of red blood cell antigen--antibody reaction was evaluated in pretransfusion compatibility tests. The evaluation was undertaken on 917 blood samples of recipients and 2450 samples of donors. Parallel study of microtest in gel and classical techniques revealed that gel technique was more sensitive than the classical one, because some antibodies of Rh, Kell and Kidd systems were found by this method exclusively. It is also more specific because a lot of unspecific reactions could be eliminated. Therefore, it was decided to use the microtest in gel for crossmatching of recipient serum against red cells from each intended donor--particularly when the patient had irregular erythrocyte antibodies. The results presented in this paper revealed that in gel is one of the most potent tests and it is the safest for routine use before transfusion. PMID- 8488737 TI - [Progress in the treatment of chronic lymphocytic leukemia]. PMID- 8488738 TI - [Myelodysplastic syndrome associated with clonal proliferation of B lymphocytes]. AB - We present an unusual case of the myelodysplastic syndrome (subtype refractory anemia with the excess of blasts in transformation--RAEB-t) associated with significant increase of IgG (4,700 mg/dl), lambda (160 U/dl) in blood serum and circulating clone of B lymphocytes SIgG, lambda, manifesting clonal rearrangement of JH domain. Peripheral blood cells of the patient showed two different chromosomal abnormalities: 47,XY, + del/8/p? and 47,XY, +22, +14, -19. We suppose that two independent neoplastic clones are developed in the described case, i.e. a population displaying markers of myeloblasts and monoblasts, and a clone of B lymphocytes. PMID- 8488739 TI - [Lymph node involvement as a primary localization of extramedullary blast crisis of chronic granulocytic leukemia (PBS)]. AB - Among 28 patients with blastic crisis of chronic granulocytic leukemia (CGL) its primary symptom in four persons was lymph nodes enlargement. In two of them histopathologic examination confirmed myeloblastic infiltration. Lymph nodes involvement appeared 1-7 months before the onset of blastic transformation in peripheral blood and bone marrow: myeloblastic in two patients, promyelocytic in one and lymphoblastic myeloblastic (bi-phenotypic) in one. Survival time from nodal infiltration was 8-16 months and from the diagnosis of CGL 16-105 months. Remission of the disease after first blastic crisis was achieved in three patients. Cytogenetic examinations disclosed double Ph chromosome in three and single Ph chromosome in one patient. PMID- 8488740 TI - Tracheo- and bronchoesophageal fistulas in Hodgkin's disease. AB - Among 330 patients with Hodgkin's disease, in five development of fistula between the respiratory and alimentary tract was observed; tracheoesophageal in three and bronchoesophageal in two patients. Generalization of the disease was the cause of fistula in three patients; it appeared as a result of necrosis of the neoplastic infiltration during cytostatic treatment or radiotherapy. In the fourth patient the fistula was of iatrogenic origin (radiation induced damage), and in the fifth it was the result of secondary neoplasm (bronchial anaplastic cancer). PMID- 8488741 TI - Staging: a neglected dimension in psychiatric classification. AB - The staging method, whereby a disorder is characterized according to seriousness, extension and features, has achieved wide currency in medicine but is currently neglected in psychiatry. Studies addressing or related to the issue of staging in schizophrenia, unipolar depression, bipolar disorder and panic disorder are discussed. The phenomenological development of these mental disorders may be categorized according to stages. PMID- 8488742 TI - Compulsory admission of psychiatric patients--an international comparison. AB - The frequency of compulsory admissions to psychiatric hospitals varies considerably between countries and regions. However, the differences are partly artificial, as the figures available are not fully comparable; this is mainly owing to differing definitions of "compulsory" and the methodological shortcomings of most studies in this field. In addition, there are also clear real differences, most of which result from different legislation and administrative regulations. Characteristics of the patient that influence the risk of compulsory admission include diagnosis and certain sociodemographic and social factors. Most studies, however, are based on highly selected populations. Furthermore, the results depend heavily on the commitment frequency of a country and therefore eventually also on the restrictiveness of legislation. The lack of methodologically sound studies, internationally comparable data and internationally published information is regrettable, as international comparison and discussion would certainly be valuable, especially for countries that are in the process of re-evaluating their commitment criteria and mental health legislation. PMID- 8488743 TI - The prevalence of transsexualism in The Netherlands. AB - The prevalence of transsexualism in the Netherlands was estimated by counting all the subjects who were diagnosed as transsexuals by psychiatrists or psychologists and were subsequently hormonally treated and generally underwent sex-reassignment surgery. At the end of 1990, 713 Dutch-born transsexuals received treatment (507 men, 206 women). This amounts to a prevalence of 1:11,900 for male-to-female transsexualism and 1:30,400 for female-to-male transsexualism (population age 15 and above in both groups). The sex ratio was about 2.5 men to 1 woman. The most important reason for this relatively high prevalence seems to be the benevolent climate for the treatment of transsexualism in the Netherlands. PMID- 8488744 TI - Prevalence of mental disorders in young adults with chronic physical diseases since childhood as identified by the Present State Examination and the CATEGO program. AB - To find out whether long-term physical disorders in childhood increase the risk for mental disorder, we interviewed 407 young adults and compared their findings to a control group of 123 age-matched controls. The overall prevalence of mental disorders according to ICD-8 classification exceeded 20% in both groups. Depression and phobic disorders were the most common diagnostic syndromes, being most prevalent in women with motor handicaps or short stature. Only 7 patients had received psychotherapy, 5 for psychotic symptoms. In conclusion, only a severe physical disease, visible and disabling for years in everyday life, seems to increase the risk for mental problems. The results demonstrate the need to improve the approach towards psychological problems in the somatic clinics treating patients with long-term physical diseases. PMID- 8488745 TI - A prevalence survey of mental disorders among children in a rural Malaysian village. AB - This is the first epidemiological survey of mental disorders among children in a Malaysian village. The WHO Research Questionnaire for Children (RQC) was used for initial screening followed by a semistructured interview, the Follow-up Interview for Children (FIC) at its second stage. Diagnosis was obtained by using Rutter's multi-axial classification. The prevalence rates obtained for the diagnostic categories were described in 3 age groups, in accordance with the age of attending school in Malaysia. Of 507 children screened aged 1-15, 6.1% were classified as having a mental disorder. PMID- 8488746 TI - A nationwide survey of seasonal affective disorder at 53 outpatient university clinics in Japan. AB - A nationwide survey of seasonal affective disorder (SAD) was performed from autumn 1990 to spring 1991 with the cooperation of 53 outpatient university psychiatric clinics in Japan. Forty-six SAD patients were identified among 5265 depressed outpatients. SAD was generally reported to occur in 1-3% of the depressed outpatients newly attending each facility. Hours of sunshine were found to be a more relevant variable influencing the prevalence of SAD than latitude or the mean temperature in December. The unexpectedly low percentage (20-30%) of SAD patients with atypical vegetative symptoms suggests that SAD patients who have no prior knowledge of SAD and those who are recruited via the media have different vegetative symptom profiles. PMID- 8488747 TI - Prevalence of tardive dyskinesia in samples of elderly people in Hong Kong. AB - The prevalence of dyskinesia was studied in 4 samples of elderly Chinese people in Hong Kong--a psychogeriatric clinic, a mental hospital, a geriatric day hospital and a senior citizen centre. Research Diagnostic Criteria were used to identify cases of tardive dyskinesia. The overall prevalence of spontaneous dyskinesia was 2.4% and tardive dyskinesia was 25.9%. The rate of spontaneous dyskinesia differs across the study samples and is related to nervous system conditions associated with increased age. On the other hand, the rate of dyskinesia associated with antidepressants may not be significantly different from that of spontaneous dyskinesia. PMID- 8488748 TI - A comparison of fluoxetine and imipramine in the treatment of outpatients with major depressive disorder. AB - A double-blind clinical trial was undertaken to evaluate the clinical efficacy and safety of fluoxetine compared with imipramine in the treatment of 59 outpatients suffering from major depressive disorder. The mean scores of all depression rating scales showed that the drugs had comparable efficacy. The side effect profile of imipramine was found to be mainly anticholinergic, which was not the case for fluoxetine, where it was mainly found to be gastrointestinal, such as nausea and diarrhoea. In both groups the total number of adverse events reported were the same. Fluoxetine treatment resulted in weight loss, whereas imipramine treatment resulted in a slight but significant weight increase. PMID- 8488749 TI - The St. George's dementia bed investigation study: cardiovascular, neurological and neuropsychological correlates. AB - The results of the cardiovascular, neurological and neuropsychological examination of a series of patients admitted to the St. George's dementia investigation bed and who later came to postmortem are compared in relation to their pathological diagnosis. Individual clinical signs were not found to differentiate between cases of dementia with vascular versus those with Alzheimer's disease pathology, although multivariate analysis suggested that there was a pattern of signs associated with cerebrovascular disease. A vascularity index was constructed from these signs; it achieved a useful level of discrimination between vascular and nonvascular causes of dementia. PMID- 8488750 TI - The distinction of bipolar II disorder from bipolar I and recurrent unipolar depression: results of a controlled family study. AB - The aim of the study was to differentiate bipolar II, bipolar I and recurrent unipolar depression by their familial load for affective disorders. Eighty bipolar, 108 unipolar, 80 control subjects and interviewed first-degree relatives were diagnosed according to Research Diagnostic Criteria using the Schedule for Affective Disorders and Schizophrenia--lifetime version. The morbid risks for bipolar I disorder were equivalent in relatives of bipolar I (3.6%) and bipolar II (3.5%) subjects and lower in relatives of unipolar subjects (1.0%). The morbid risks of relatives for bipolar II disorder distinguished bipolar II subjects (6.1%) from bipolar I subjects (1.8%), from unipolar depressives (0.3%) and from controls (0.5%). To promote further evaluation, bipolar II disorder should be included in DSM-IV as a distinct diagnostic category. PMID- 8488751 TI - Clinical, endocrine and neurochemical effects of moclobemide in depressed patients. AB - The clinical efficacy of the monoamine oxidase A inhibitor moclobemide and its effect on the dexamethasone suppression test (DST) and plasma and urine methoxyhydroxyphenylglycol (MHPG) were investigated in 26 depressed patients during a 4-week clinical trial. Fourteen patients (54%) responded favourably to the treatment (50% or more reduction of the Hamilton Rating Scale for Depression score). All (8) patients with an abnormal DST responded to treatment; 11 of 16 patients with a normal DST did not respond. Patients with low pretreatment MHPG excretion, according to the median value, were more frequently treatment responders. Plasma and urine MHPG were significantly decreased by treatment. The results indicate that low excretion of MHPG and cortisol nonsuppression may be considered as predictors of favourable clinical response to moclobemide treatment. PMID- 8488752 TI - Developmental changes of aminopeptidase activity in the cortex of the cat brain. AB - Aminopeptidase activity has been proposed as a candidate regulator of the degradation of several neuroactive peptides. In this paper, possible changes in Lys-, Arg-, Asp- and Tyr-aminopeptidase activities in the cat brain neocortex (frontal, parietal, area 17 and areas 18 and 19 as a whole) were examined during two of the first stages of the critical developmental period (15 and 30 days postbirth). Aminopeptidase activities were studied by measuring the rate of hydrolysis of the artificial substrates Lys-, Arg-, Asp- and Tyr-2-naphthylamides (fluorimetrically detected in triplicate). Lys- and Arg-aminopeptidase activities do not show significant changes between the first the second stage in any of the cortical regions assayed. On the contrary, in all the cortical structures, activity with Tyr-2-naphthylamide shows significant increase with age. In contrast, the activity of Asp-aminopeptidase shows significant decreases on the 30th day (except in area 17). It is suggested that these activities play a part in the neurochemical changes that take place during cat brain maturation. PMID- 8488753 TI - Influence of tongue myoblasts on rat dissociated hypoglossal motoneurons in culture. AB - Hypoglossal motoneurons of 1-2 day-old newborn rats were retrogradely labelled following an injection of fluorescent latex microspheres and carbocyanines. Motoneurons were identified among the cell population of the hypoglossal nuclei during the dissociation and culture procedures. DiI labelled motoneurons could be maintained in culture on poly-L-lysine coating and Dulbecco Minimum Essential Medium with Ham F12 complement, supplemented with additives and 3% fetal calf serum. Neuronal survival as well as extension of neurites, identified by their content in DiI or by the presence of choline acetyltransferase immunoreactivity, was increased in the presence of myoblastic satellite cells originating from tongue muscular explants. Co-cultures of dissociated hypoglossal cells with tongue myoblasts revealed the presence, after 10-15 days in culture, of structures morphologically similar to neuromuscular junctions. Such re-innervated muscular fibres exhibited muscular contractions which were blocked by curare and augmented by glutamate applications, demonstrating the functionality of the observed re-innervations. PMID- 8488754 TI - Mesenteric neurons in the adult rat are responsive to ileal treatment with benzalkonium chloride. AB - The application of a 2 mM solution of the cationic surfactant benzalkonium chloride (BAC) to an ileal segment produced a selective and extensive myenteric denervation. The aim of the present study was to investigate whether such a selective unbalance of the enteric nervous system in the adult rat elicited any plastic response within the mesenteric nervous structures contacting it. Acetylcholinesterase (AChE) staining, beta-nicotinamide adenine dinucleotide (NADH) and beta-nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and glyoxylic acid-induced fluorescence were performed on whole mount preparations of myenteric plexus and mesenteric nerves. In both control and BAC-treated animals nervous elements were detected along the mesenteric nerves. Although rather similar in position, shape and size, these neurons displayed striking differences with regard to their arrangement and density per nerve. In the controls, few small aggregates of neurons could be detected; more commonly, isolated nerve cell bodies were scattered along the nerve trunks. In the BAC treated animals, numerous spherical or spindle-shaped clusters of neurons were located along the nerves; the mean neuronal density per nerve displayed a two five-fold increase over the control values. The observed changes within the mesenteric nerves might be involved in an attempt at reinnervation of the BAC treated intestinal segments from extra-enteric sources. PMID- 8488755 TI - Culture of rat brain preoptic area neurons: effects of sex steroids. AB - The aim of the present study was to investigate the direct effects of testosterone (T), estradiol-17 alpha (E2) and 5 alpha-dihydrotestosterone (5 alpha-DHT) on the survival of neurons and the morphology of neuronal processes (the total process length, the number of processes and the number of process branchings) of the cells derived from neonatal rat preoptic area (POA) to analyze the bases of morphological sexual dimorphism of the POA. The POA cells were exposed to sex steroids during 2-14 days of culture in serum-free medium. Neuronal survival was significantly greater in cultures treated with 1.0 nM T than controls. Although T at any concentration tested (0.1, 1.0 or 10.0 nM) failed to affect the mean value of the process length, a significant difference was observed in the frequency distribution of total process length between 1.0 nM T-treated cultures and control cultures. By 1.0 nM T, the number of process branchings was also significantly increased. In contrast, the number of neurons and the total process length of neurons were not affected by 5 alpha-DHT. However, the number of process branchings was significantly increased by 0.1 nM 5 alpha-DHT. E2 had no significant effect on any of these parameters. These results suggest that T directly enhances the survival of neurons and increases the dendritic and/or axonic field of the POA, which serves, at least partly, for the development of morphological sexual dimorphism in the rat. PMID- 8488756 TI - Expression of NCAM mRNA and polypeptides in aging rat brain. AB - In aging brain, degenerative as well as compensatory regenerative processes are believed to occur. The neural cell adhesion molecule NCAM is involved in developmental and regenerative processes in the brain. However, the role of NCAM in aging brain has not been characterized. In this study, the expression of NCAM mRNAs and polypeptides was investigated in aging rat brain. The 7.4 and 6.7 kb NCAM mRNAs were selectively downregulated during postnatal development, and the 5.2 and 2.9 kb NCAM mRNAs were upregulated. However, from postnatal day 40 to old age no change in NCAM mRNA classes was observed. The fraction of NCAM mRNA containing the VASE exon increased postnatally but remained stable during adult life. VASE, which is believed to modulate the binding capacity, seemed to be relatively more abundant in the 7.4 and 6.7 kb NCAM mRNAs, encoding transmembrane NCAM forms, than in the 5.2 and 2.9 kb NCAM mRNAs, coding for glycosyl phosphatidylinositol (GPI) linked NCAM. Conversely, insertion of exons a and AAG between exons 12 and 13, a region containing two fibronectin type III repeats, seemed to be more pronounced in 5.2 and 2.9 kb NCAM mRNAs than in the 7.4 and 6.7 kb mRNAs. During postnatal development an increase in the fraction of 6.7 kb NCAM mRNA containing the exons a and AAG was observed. However, during aging the fraction of NCAM mRNAs containing this exon combination seemed constant. At the protein level, NCAM-A was downregulated both during development and aging. No changes were observed during aging in the composition of soluble NCAM forms in the brain, cerebrospinal fluid or blood plasma. The amount of NCAM in rat brain decreased during postnatal development, but remained at a constant level from postnatal day 40 to old age. To conclude, several changes in NCAM expression occur during early postnatal development emphasizing the important role of this molecule in the morphogenetic processes. During aging, a significant selective downregulation of NCAM-A was observed indicating that in general only minor regenerative processes occur in the brain. PMID- 8488757 TI - Effect of CDP-choline treatment on mitochondrial and synaptosomal protein composition in different brain regions during aging. AB - Several age-dependent modifications of inner mitochondrial membrane and synaptosomal plasma membrane proteins from different brain regions of 4-, 12-, 18 and 24-month-old male Wistar rats, were observed. Some proteins, identified by immunoblotting assay as various subunits of mitochondrial respiratory chain complexes and calmodulin, were particularly impaired. Chronic treatment with CDP choline at a dose of 20 mg/kg body weight per day for 28 days caused significant changes in the amounts of several of the above mentioned proteins. Most of the proteins, which decreased during aging, showed a significant increase after CDP choline treatment compared with the corresponding control values at the same age. The effect of CDP-choline might be due to: the increased availability of cytidylic nucleotides, which in the brain are present in limited amounts compared to the other nucleotides; the increased content of total adenine nucleotides; the improvement of brain energy metabolism. PMID- 8488758 TI - Laminin concentrations in serum and cerebrospinal fluid in aging and Alzheimer's disease. AB - Laminin, a basement membrane protein, and a potent promoter of neurite outgrowth, surrounds all peripheral nerves. It appears in the central nervous system during development and reappears in response to injury. In Alzheimer's disease (AD), there is a progressive loss of neurons in specific areas of the brain along with the presence of an increased number of senile plaques and neurofibrillary tangles. Laminin levels have been shown to be increased in injury, so we undertook to examine levels of laminin by radioimmunoassay (RIA), in cerebrospinal fluid and serum of patients with AD and age-matched controls. No difference in the CSF and serum laminin concentrations was found between Alzheimer's disease and age-matched controls. We found a lack of correlation between severity of clinical dementia and laminin concentrations. Finally, we show that the CSF and serum laminin concentrations increase with age. PMID- 8488759 TI - [Pulmonary sequestration. Report of a clinical case]. AB - Concerning a clinical situation of intralobar pulmonary sequestration, in a seventeen year old young man, the authors review this nosological entity. They emphasize the importance of the complementary examens of diagnosis, namely of thoracic scan and aortography, for the establishment of the said diagnosis. PMID- 8488760 TI - [The adoption of heroin addicts++ as a strategy of ambulatory treatment]. AB - The authors describe the ambulatory treatment of a young man, the son of a divorced mother, where they used a methodology called Combined Treatment of Heroin Addicts, which was done in stages. They used family sessions, with a concomitant hearing of the patient alone, combined with the use of an opioid antagonist, called naltrexone. The young man was adopted by an uncle, married to his mother's sister, because his mother was divorced, living alone, and was too old to support, contain and provide her son with the necessary basis for treatment. The uncle assumed the tutorage of the case completely and gave his nephew the basis for identification and psychic maturation. The young man has now a year of treatment with a satisfactory evolution: he has had good results in his studies, has achieved good family and social integration, and does not use heroin. PMID- 8488761 TI - [Letter concerning the article: Drug surveillance: concepts, objectives, and methods (1992; 11:595-602)]. PMID- 8488762 TI - [Imaging methods in the study of urinary tract infections in children]. AB - When studying a child with urinary tract infection it is important to detect and localize any renal (scar) or urologic anomaly. Here we study the information obtained using: renal and vesical ultrasound (US), DMSA scan and radiologic or isotopic cystogram. METHODS: We studied 148 children with more than one urinary tract infection and/or pyelonephritis; their mean age was 35.9 months (1-148 months); 55% were girls. The three diagnostic examinations--US, DMSA scan and cystogram were made in the order; the DMSA scan or cystogram was never made sooner than one month after the UTI. RESULTS: In 42% of the children the three exams were normal; 4 of these children had another UTI and the urodynamic study revealed vesical disfunction. 11% had renal scars (DMSA scan) with normal US and cystogram; 30% had VUR, 50% of which had an altered US and 57% had renal scars on the DMSA scan. 12% of the children had an altered US with a cystogram showing no VUR; 66% of these had renal scars. 4% had vesical anomalies on the US and cystogram. CONCLUSION: The three exams chosen were able to direct the diagnostic approach of UTI, being sufficient in most of the cases. We would like to emphasize the importance of the DMSA scan in diagnosing unsuspected renal scars. PMID- 8488763 TI - [The role of radiotherapy in soft tissue sarcomas. Retrospective analysis of 115 cases treated from 1979 to 1988]. AB - In this study was analysed the results of a group of patients with soft tissue sarcomas treated at the IPOFG Center of Lisbon from January 1979 to December 1988. All these cases were referred to the Radiotherapy Department for radiation treatment which was given in 84% of the patients as a complement to surgery and in 16% was either combined with chemotherapy or given as exclusive therapy. The immediate results showed complete remission in 79% and partial remission in 7% of the cases. Seventeen per cent of the patients developed relapses and 28% distant metastases after a free interval of 27.7 and 19.6 months respectively. The five year actuarial survival rates were 73.3% for the patients without recurrences, 55.4% for the patients with relapses and 21.4% for disseminated disease. The long term results varied according to the localization of the tumor, the stage of the disease, the age of the patient, the extension of surgery, the histologic type and the radiation dose. Five year actuarial survival rates also varied with the type of treatment (63.8% for surgery followed by radiotherapy with or without chemotherapy and 50.8% for preoperative radiotherapy and surgery with or without adjuvant chemotherapy). Radiotherapy with or without chemotherapy, in inoperable patients, was generally useful because it improved the quality of life, saving about 25% of the inoperable cases. Treatment related complications were minimal. PMID- 8488764 TI - [Disodium pamidronate (APD) in the treatment of bone metastases]. AB - Diphosphonates are potent inhibitors of bone resorption, they have been evaluated in several clinical trials for bone metastases. We performed a clinical study to evaluate the therapeutic effect of Disodium Pamidronate over pain and radiologic evolution in bone metastases (Breast Cancer and Multiple Myeloma patients). The results regarding the first 10 patients concluded that there is good drug tolerability and significant analgesic activity in 6 patients, with sclerosis of lytic skull lesions in one breast cancer patient. PMID- 8488765 TI - [Hepatitis C virus infection in chronic asymptomatic carriers of HBs antigen]. AB - The objectives of the study were to evaluate the prevalence, the incidence and the clinical significance of antibodies to hepatitis C virus in HBsAg chronic carriers. The evaluation of Stored sera was combined with the follow-up of a cohort os cases observed in a referral-based university hospital. A total of 183 HBsAg asymptomatic chronic carriers were identified during routine screening and followed for a mean period of 3.8 years. Stored sera and sera obtained during follow-up were tested for anti-HCV using ELISA. Second generation RIBA (Ortho) was used as a possible confirmatory test. Demographic data and risk factors were assessed using a standard questionnaire. The prevalence of HCV infection in HBsAg chronic carriers was 2.7% (95% CI: 1.2%-6.3%), higher in male than female (3.1% vs 1.8%, p = 0.52) and also higher than the one found in voluntary blood donors from the same region. Only 3 out of 5 ELISA-positive cases were RIBA-positive. Patients positive for both types of virus more frequently admitted drug abuse. The presence of anti-HCV was not significantly related to the histologic severity. During follow-up no new cases of infection were found. CONCLUSIONS: The prevalence of HCV infection in asymptomatic chronic carriers is higher than in blood donors but lower than previously reported for other populations of chronic hepatitis B cases. HCV infection was not found responsible for the frequency or the type of lesions observed im these HBsAg chronic carriers. PMID- 8488766 TI - [Bone marrow transplantation with major ABO incompatibility. Experience at the bone marrow transplantation unit of the Center of Lisbon at the IPOFG]. AB - Thirteen patients submitted to major ABO incompatible, HLA A and B identical, mixed lymphocyte culture negative bone marrow transplantation (BMT) were retrospectively evaluated. Gravity sedimentation by hydroxyethyl starch was used in almost all cases to deplete erythrocytes from bone marrow (12/13): a removal rate or 90%--corresponding to an erythrocyte residual volume of 27.4 rate ml--and a nucleated cell recovery of 76% (mean values) were obtained. All patients underwent a hyperhydration regimen and received corticosteroid prophylaxis before bone marrow infusion. Considering the most important immunohematological problems associated to this type of transplant we verified that seven patients developed minor complications, and among them only one had long term consequences. In comparison with the control group, ABO identical and with minor incompatibility, the study group had delayed onset of erythropoiesis and needed greater erythrocyte transfusion support. We concluded that major ABO incompatibility does not constitute a drawback to BMT success in most patients. PMID- 8488767 TI - [Giant cell arteritis (Horton's disease): report of 18 cases]. AB - The authors present and comment on 18 cases of Giant-cell arteritis observed in an Internal Medicine Department between 1984 and 1991 with emphasis on clinical aspects and diagnostic considerations, on the occult presentation forms and, finally, on two cases with peripheral neuropathy. The clinical manifestations were: headache (78%), general non-specific symptoms (78%), polymyalgia rheumatica (61%), sudden blindness (33%), local temporal signs (28%), jaw pain (24%), articular complaints (17%) and peripheral neuropathy (12%). PMID- 8488768 TI - [Prognostic systems in intensive care: general principles, development, and clinical applications]. AB - In this review article, we present the need for prognostic scoring in clinical medicine, specially in Intensive Care Medicine (ICM). The general principles of prognostication in ICM are discussed, and three general scoring systems are presented: ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION (APACHE) in its 3 versions, SIMPLIFIED ACUTE PHYSIOLOGY SCORE (SAPS) and MORTALITY PREDICTION MODEL (MPM). The use of these prognostic systems is then evaluated not only as a support for medical decision-making, and resource allocation, but also as a tool for clinical studies in terms of patient randomization. Finally, the future developments and clinical application of these risk stratification systems are presented and discussed. PMID- 8488769 TI - [Biological rhythms in man. Particular aspects in medicine]. AB - The concepts of chronobiology and chronopharmacology have become more and more important in medical practice nowadays. Today, the circadian variation in blood pressure and heart rate as well as in the occurrence of acute cardiovascular disease is quite obvious (ischemia, infarction, stroke and sudden death). However, biological rhythms are also present in episodes of dyspnoea in nocturnal asthma, in hormonal pulses, in the organization of the immunological system and in the processes of cellular proliferation. These acknowledgments have been leading to changes in our therapeutical approaches implying the definition of correct anti-hypertensive and anti-ischemic strategy was well as in the use of xanthins, corticosteroids, immunomodulators and cytostatics. PMID- 8488770 TI - Clinical applications of Doppler coronary flow reserve measurements. AB - The development of a subselective coronary Doppler catheter coupled with pharmacologic coronary resistance vessel vasodilation has enabled clinicians to assess coronary vasodilator reserve in humans. This technique has proven useful in the clinical management of patients with a variety of cardiologic problems. This review describes usefulness of Doppler measurements of coronary flow reserve for (1) functional assessment of coronary stenoses of intermediate severity; (2) determination of the need for lesion-specific interventional therapy; (3) assessment of the severity of saphenous vein bypass graft and graft-native vessel anastomotic lesions; (4) assessment of the coronary microcirculation. PMID- 8488771 TI - Applications of coronary flow velocity during angioplasty and other coronary interventional procedures. AB - Previous studies utilizing Doppler catheters to assess blood flow immediately following coronary artery interventions have failed to demonstrate significant improvement in proximal coronary artery velocities or vasodilator reserve. Measurement of blood flow velocity, flow reserve, and the phasic diastolic/systolic velocity ratio in the distal coronary artery has been performed following various interventional procedures utilizing a low profile (.018 in) Doppler angioplasty guidewire. Following balloon angioplasty in 38 patients, average peak velocity increased significantly from 19 +/- 12 to 35 +/- 16 cm/sec in the distal coronary artery. The diastolic/systolic flow ratio improved from 1.3 +/- 0.5 to 1.8 +/- 0.5 and coronary flow reserve remained unchanged. Similar improvement in distal mean velocities (200%) versus proximal mean velocities (90% increase), and improvement in phasic velocity patterns, total velocity integral, and peak diastolic velocity were also noted in a separate study of 29 patients, before and after balloon angioplasty. Following excimer laser angioplasty in 10 patients, average peak velocity in the distal coronary artery was noted to increase from 6.3 to 13.0 cm/sec following laser alone, with a further increase to 20.6 cm/sec following adjunctive balloon angioplasty. The diastolic/systolic flow ratio increased from a mean value of 1.1 to 2.0 following laser recanalization, with a further increase to 2.9 following adjunctive balloon angioplasty. Following directional coronary atherectomy only modest improvement in distal average peak velocity was noted (24.7 to 31.2 cm/sec), with no significant change in diastolic/systolic velocity ratio (1.78 vs 2.04) immediately following the procedure. Measurement of distal flow velocity parameters performed immediately following coronary interventions may prove useful in assessing the hemodynamic result of these interventions and may prove useful in clinical decision making. PMID- 8488772 TI - Assessment of angiographically intermediate coronary artery stenosis using the Doppler flowire. AB - Determination of the clinical and hemodynamic significance of coronary stenoses is often difficult and inexact. Angiography and coronary vasodilator reserve have been shown to be imperfect tools to determine the physiologic significance of coronary stenoses. Spectral flow velocity data, both proximal and distal to coronary stenoses, using an 0.018-in intracoronary Doppler-tipped angioplasty guidewire, were compared to translesional pressure gradients and angiography during cardiac catheterization. Patients were divided into 2 groups based on resting translesional gradients: Group 1 had gradients < 20 mm Hg and group 2 had gradients > or = 20 mm Hg. Proximal average peak velocity, diastolic velocity integral, and total velocity integral were statistically significantly lower in Group 1. The distal average peak velocity, and diastolic and total velocity integrals were all significantly (p < 0.01) decreased in patients with gradients > 20 mm Hg (group 2). The ratio of proximal-to-distal total flow velocity integral was also higher in group 2 patients (2.3 +/- 0.9) compared with group 1 (1.1 +/- 0.2; p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal-to-distal total flow velocity integrals (r = 0.8, p < 0.001) with a weaker relationship between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). Angiography was a poor predictor of translesional gradients in angiographically intermediate stenoses (range 50-70%; r = 0.2, p = NS), while the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488773 TI - Coronary flow velocity dynamics in normal and diseased arteries. AB - Distal coronary flow velocity measurements were previously limited to open heart or experimental procedures. Unlike previous Doppler catheter techniques, a Doppler angioplasty flow wire permits flow velocity measurements in both the proximal and distal segments of normal and diseased coronary arteries. In order to determine the potential clinical application of the Doppler flow wire, we performed baseline and hyperemia flow velocity measurements in proximal and distal segments of 20 angiographically normal arteries (right coronary = 8; left circumflex = 7; left anterior descending = 5) and 29 significantly stenosed arteries. All 3 normal coronary arteries had a diastolic-predominant pattern in both proximal and distal segments; the right coronary artery showed significantly less diastolic predominance. The coronary vasodilator reserve was similar in all three normal coronary arteries, and in the proximal and distal arterial segments. Abnormal arteries had significantly lower coronary vasodilator reserve (normal vs abnormal, 2.3 +/- 0.8/1.6 +/- 0.7; p < 0.02). Normal arteries had preservation of velocity parameters in the distal segments; abnormal arteries had a significant decrease in distal velocity parameters. The proximal-to-distal velocity ratio was thus significantly higher in abnormal arteries (2.4 +/- 0.7 vs 1.1 +/- 0.2; p < 0.001). The coronary vasodilator reserve in proximal and distal arteries--in addition to the proximal to distal velocity ratio--may provide functional and hemodynamic data complementary to coronary angiography in the assessment of coronary artery stenosis. PMID- 8488774 TI - Quantitating coronary collateral flow velocity in patients during coronary angioplasty using a Doppler guidewire. AB - Quantitation of coronary collateral flow in patients has been limited to angiographic techniques, which are subject to well-known methodologic limitations. The use of a Doppler-tipped angioplasty guidewire permits measurement of both antegrade and retrograde flow distal to totally or subtotally occluded vessels that may be supplied with acutely recruitable or angiographically mature collateral conduits. Using coronary flow velocity as an indicator of collateral flow, retrograde flow velocity was quantitated in 17 patients. Mean collateral flow velocity was approximately 30% of normal postangioplasty antegrade flow velocity. The phasic pattern of collateral flow was highly variable, but the retrograde diastolic and systolic flow velocity integrals were 20% and 40% (respectively) of post-procedure antegrade flow velocity. Preliminary studies with pharmacologic stimulation of the contralateral supply artery suggests that collateral flow is not increased by intracoronary nitroglycerin (200 micrograms) or adenosine (12 micrograms), but may be markedly augmented during mechanical stimulation of balloon occlusion. These data represent the first in a series of quantitative observations on control of the coronary collateral circulation in humans. Future investigations using the Doppler Flowire (Cardiometrics) will enhance understanding of factors modulating ischemia through collateral supply. PMID- 8488775 TI - Intracoronary pressure and flow velocity with sensor-tip guidewires: a new methodologic approach for assessment of coronary hemodynamics before and after coronary interventions. AB - The use of miniaturized pressure and velocity sensors mounted on angioplasty guidewires allows the simultaneous measurement of coronary blood flow velocity and transstenotic pressure gradient, 2 parameters that, combined, should perfectly characterize stenosis hemodynamics. The aim of this article is assessment of the changes in coronary blood flow velocity observed with a Doppler tipped angioplasty guidewire in 35 patients undergoing balloon angioplasty. We also report our initial experience in 16 patients with the combined use of sensor tip pressure and Doppler guidewires, and we discuss the application of new methodologic approaches for the study of the coronary circulation allowed by these techniques, such as the instantaneous assessment of the flow velocity/pressure and pressure gradient/flow velocity relations. Before and after angioplasty, flow velocity measurements were obtained distal to the stenosis, both in baseline conditions and after intracoronary injection of 8-12.5 mg of papaverine. The Doppler guidewire was left in place during the dilation procedure and the Doppler signal was continuously recorded during balloon inflation and after deflation to monitor the development of collateral flow, the restoration of flow after balloon deflation, the phase of postocclusive reactive hyperemia, and, incidently, the development of flow-limiting complications. Merits and pitfalls of several flow velocity parameters (average peak velocity, coronary flow velocity reserve, diastolic/systolic velocity ratio), as well as of parameters derived from the combination of pressure and velocity measurements (transstenotic pressure gradient/flow velocity relation and instantaneous diastolic hyperemic flow velocity/pressure relation) were evaluated in 35 patients with, and 37 without, significant coronary stenoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488776 TI - Maximal blood flow velocity in severe coronary stenoses measured with a Doppler guidewire. Limitations for the application of the continuity equation in the assessment of stenosis severity. AB - In vitro and animal experiments have shown that the severity of coronary stenoses can be assessed using the continuity equation if the maximal blood flow velocity of the stenotic jet is measured. The large diameter and the low range of velocities measurable without frequency aliasing with the conventional intracoronary Doppler catheters precluded the clinical application of this method for hemodynamically significant coronary stenoses in humans. This article reports the results obtained using a 12 MHz steerable angioplasty guidewire in a consecutive series of 52 patients undergoing percutaneous coronary angioplasty (61 coronary stenoses). The ratio between coronary flow velocity in a reference segment and in the stenosis was used to estimate the percent cross-sectional area stenosis. A Doppler recording suitable for quantitation was obtained in the stenotic segment in only 10 of 61 arteries (16%). The time-averaged peak velocity increased from 15 +/- 5 to 115 +/- 26 cm/sec from the reference normal segment to the stenosis. Volumetric coronary flow calculated from the product of mean flow velocity and cross-sectional area was similar in the stenosis and in the reference segment (33.2 +/- 14.9 vs 33.5 +/- 17.0 mL/min, respectively, difference not significant). The percent cross-sectional area stenosis and minimal luminal cross-sectional area derived from the Doppler velocity measurements using the continuity equation and calculated with quantitative angiography were also similar (Doppler, 86.7 +/- 5.1% and 1.00 +/- 0.48 mm2; quantitative angiography, 85.9 +/- 7.9% and 1.02 +/- 0.50 mm2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488777 TI - Coronary artery flow monitoring following coronary interventions. AB - Technologic innovations have made it possible to measure coronary artery blood flow in awake patients. Both flow velocity as well as flow reserve can be assessed. In particular, the period of time immediately following coronary interventions offers a unique opportunity to study important features of coronary flow behavior. In 22 patients, coronary flow reserve was measured before and after an intervention, either angioplasty or atherectomy, using a 0.018-in Doppler guidewire (Flowire). The minimum lumen diameter (MLD) was increased from 1.0 +/- 0.4 to 1.7 +/- 0.4 mm, while coronary flow velocity increased significantly, rising from 29 +/- 13 to 39 +/- 14 cm/sec (p < 0.025). The maximum hyperemic velocity also increased, from 44 +/- 16 to 69 +/- 21 cm/sec. Using only the preintervention or postintervention values, the flow reserve ratio was 1.53 +/- 0.4 prior to intervention and 1.84 +/- 0.5 after intervention (p = nonsignificant). However, the post-intervention value may have been artifactually reduced by the fact that both resting as well as hyperemic velocities increased. When the post-intervention flow reserve ratio was recalculated, using the preintervention resting value, flow reserve ratio was seen in increase from 1.53 +/- 0.4 to 2.73 +/- 1.2 (p < 0.001). Measurements of coronary flow in the postintervention period also revealed several interesting phenomena. Spasm of a coronary artery was documented, and its resolution in response to intracoronary nitroglycerin was observed. Elastic recoil following angioplasty was documented by gradual decline in coronary flow over 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488778 TI - Combined physiologic and anatomic assessment of percutaneous revascularization using a Doppler guidewire and ultrasound catheter. AB - Previous investigations have established the utility of intravascular ultrasound (IVUS) examination for the evaluation of arterial dimensions and qualitative changes following percutaneous revascularization. More recently, the feasibility of obtaining intravascular physiology findings before and/or after percutaneous revascularization by use of an intravascular Doppler Flowire (Cardiometrics) has been demonstrated. Accordingly, we investigated the feasibility of using this combined physiologic/anatomic approach to evaluate individuals undergoing percutaneous revascularization of stenotic or occluded coronary and peripheral arteries. A total of 76 patients were evaluated using the Flowire to guide an IVUS catheter. Revascularization of coronary and peripheral vascular stenoses and/or occlusions was achieved in these patients by balloon angioplasty, directional atherectomy, excimer laser angioplasty, and thrombolytic therapy, alone or in combination. Physiologic findings obtained with the Flowire reinforced conclusions regarding morphologic severity of candidate stenoses and anatomic adequacy of revascularization following IVUS examination. In certain ambiguous cases, information gained by one modality clarified information obtained with the other. Finally, one modality may also serve as an alternative when logistics preclude the serial use of both. The preliminary experience obtained in this feasibility trial confirmed that IVUS and the Flowire may be combined to assess both candidate lesions as well as postprocedural patency in patients undergoing percutaneous revascularization. The combination of anatomic and physiologic data available from IVUS and Flowire provides a far more sensitive and possibly more accurate analysis of the adequacy of revascularization than has been possible by angiography alone. The extent to which such a detailed investigation is required to optimize interventional therapy on a routine basis is the subject of subsequent investigations. PMID- 8488779 TI - Poverty, health, and children: a second look. PMID- 8488780 TI - Youth alienation as an emerging pediatric health care issue. Update. PMID- 8488781 TI - Prevention and adolescent health. Commentary on progress of the past 2 years. PMID- 8488782 TI - Redoing the health care quilt. A progress report. PMID- 8488783 TI - Academic pediatrics and the health of medically underserved children in America. PMID- 8488784 TI - Improving health care provision to neonates in the United States. PMID- 8488785 TI - Child abuse and neglect. Follow-up. PMID- 8488786 TI - Homeless children. Two years later. PMID- 8488787 TI - Homeless children in America. Taking the next step. PMID- 8488788 TI - Pediatric human immunodeficiency virus revisited. PMID- 8488789 TI - Pediatric human immunodeficiency virus infection and the acquired immunodeficiency syndrome. A progress report. PMID- 8488790 TI - Update on the American Academy of Pediatrics activities to achieve universal access to health care for all children. PMID- 8488791 TI - Growing neglect of American children. PMID- 8488792 TI - Update on the research agenda and care for the poor child. Steps forward, steps backward. PMID- 8488793 TI - Progress in resident education on serving the underserved. PMID- 8488794 TI - Poverty and cardiac disease in children revisited. PMID- 8488795 TI - Caring for indigent children with rheumatologic diseases. The challenge continues. PMID- 8488796 TI - What will it take to fully protect all American children with vaccines? An update. PMID- 8488797 TI - Older adolescents, a group at special risk. What have 2 years achieved? PMID- 8488798 TI - Update on children's health care. PMID- 8488799 TI - Children's services in an era of budget deficits. PMID- 8488800 TI - Behavioral adaptation to human immunodeficiency virus-seropositive status in children and adolescents with hemophilia. AB - OBJECTIVE: To examine the behavioral adaptation to human immunodeficiency virus (HIV)-seropositive status, as defined by parental report, in children and adolescents with hemophilia. RESEARCH DESIGN: A clinical descriptive study of two groups of patients as part of a longitudinal design. SETTING: A university-based comprehensive hemophilia center and department of neurology acquired immunodeficiency syndrome dementia center. PATIENTS: Forty-six male children with hemophilia divided into two groups based on HIV-seropositive (n = 18) or seronegative (n = 28) status. None of the patients were symptomatic for acquired immunodeficiency syndrome. SELECTION PROCEDURES: All pediatric patients with documented factor VII or IX deficiency aged between 4 and 19 years at study onset and their families were eligible to participate. All subjects were recruited without regard to human immunodeficiency virus status. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Profiles of behavioral adjustment were obtained from parents' reports on the Child Behavior Checklist for the HIV-seropositive and HIV seronegative groups. The two groups did not differ on any of the major indexes of the Child Behavior Checklist, even after adjusting for maternal education and severity of hemophilia. There also was no difference between the groups when individual cases were examined for the number of child behavior checklist scales falling within a clinically significant range. CONCLUSIONS: The current findings fail to confirm any clear evidence of behavioral problems in an asymptomatic group of HIV-seropositive children and adolescents with hemophilia. PMID- 8488801 TI - Health maintenance organizations and children with special health needs. A suitable match? AB - OBJECTIVE: To address how well health maintenance organizations (HMOs) meet the needs of almost 700,000 children with disabilities due to chronic conditions enrolled in these plans. DESIGN: A cross-sectional survey. MEASUREMENTS/MAIN RESULTS: Health maintenance organizations offered better protection than conventional plans against out-of-pocket expenses and were much more likely than fee-for-service plans to cover ancillary therapies, home care, outpatient mental health care, and medical case management. In addition, few HMOs maintained exclusions for preexisting conditions. Other aspects of HMO policies, however, were found to operate against the interest of families with chronically ill children. In particular, HMOs commonly made specialty services available only when significant improvement was expected within a short period. Also, HMOs typically placed limits on the amount and duration of mental health, ancillary services, and certain other services frequently needed by chronically ill children. Probably the most serious problems for chronically ill children enrolled in HMOs were the lack of choice among and access to appropriate specialty providers. PARTICIPANTS: Individual HMO plans. SELECTION PROCEDURE: A sample of 95 geographically representative HMOs were selected; 59 (62%) responded. INTERVENTIONS: None. CONCLUSIONS: Health maintenance organizations offer several advantages over traditional fee-for-service plans for families whose children have special health needs. However, the results also indicate that HMOs do not always operate effectively as service provision systems for these children. To a large extent, the availability and quality of services available to a child with special needs is likely to depend on the parents' ability to maneuver within the system. PMID- 8488802 TI - The value of urinary growth hormone determination for assessment of growth hormone deficiency and compliance with growth hormone therapy. AB - OBJECTIVE: To compare the 24-hour integrated concentrations of plasma growth hormone with growth hormone levels in a simultaneously collected sample of urine. SETTING: Pediatric endocrine diagnostic unit. PATIENTS: Forty-six children (41 male and five female) aged 6 to 19 years underwent measurement of integrated concentrations of growth hormone and simultaneous urine collection. MEASUREMENTS AND RESULTS: Integrated concentration of plasma growth hormone was correlated with urinary growth hormone levels from both the 24-hour (r = .67; P < .0001) and 12-hour overnight (r = .52; P < .001) measurements. Peak growth hormone response to paired stimulation was not correlated with either the 24-hour (r = .26; P < .23; n = 28) or 12-hour (r = .16; P < .48; n = 28) urinary growth hormone levels. The mean 24- and 12-hour urinary growth hormone levels for the patients with normal integrated concentrations of growth hormone were significantly higher than those in patient groups having subnormal integrated concentrations of growth hormone (P < .05). However, there was considerable overlap in the 12- and 24-hour urinary growth hormone levels between the patients with normal and those with subnormal integrated concentrations of growth hormone. Only one patient who had subnormal integrated concentrations of growth hormone had a 24-hour urinary growth hormone level higher than 9 ng, and none had a 12-hour urinary growth hormone level higher than 7 ng. The mean 12- and 24-hour urinary growth hormone levels were significantly higher in patients who received growth hormone injection than in those with normal spontaneous integrated concentrations of growth hormone and had no overlap with patients who had subnormal integrated concentrations of growth hormone. CONCLUSIONS: (1) Urinary and integrated concentrations of plasma growth hormone are correlated; (2) patient diagnoses based on integrated plasma growth hormone levels exhibit a high degree of overlap of urinary growth hormone; and (3) urinary growth hormone levels can serve to monitor compliance with growth hormone therapy. PMID- 8488803 TI - Measles, mumps, and rubella antibodies in vaccinated Baltimore children. AB - OBJECTIVE: To determine quantitative measles, mumps, and rubella serum antibody levels as a function of time since vaccination in a sample of vaccinated Baltimore children. DESIGN: Cross-sectional serologic survey. SETTING: Pediatric outpatient departments at the University of Maryland Medical Center, Baltimore. PARTICIPANTS: One hundred seventy children, ranging in age from 1.5 through 16 years, who had measles, mumps, and rubella vaccination between ages 12 and 18 months. RESULTS: Serum antibody levels to measles and rubella declined with increasing time since vaccination. However, no such decline in antibody levels to mumps was observed. Children who were vaccinated between ages 12 and 14 months did not have lower antibody levels than children who were vaccinated at age 15 months or older. CONCLUSIONS: In areas free from natural disease, antibody levels resultant from measles, mumps, and rubella vaccine are likely to decline with advancing age. Revaccination with measles, mumps, and rubella vaccine may boost falling antibody titers. PMID- 8488804 TI - Taxicabs and child restraint. AB - For young urban families who may not own a car, taxicabs are a common mode of transportation. We surveyed the frequency of taxicab use involving children younger than age 4 years in a Baltimore, Md, clinic population and studied pediatric occupant safety issues, including taxicab child restraint law exemptions, taxicab occupant morbidity/mortality data, and taxicab child restraint device availability. In our inner-city clinic, 84 (78%) of 108 families reported that they did not own a car and 64 (76%) of those without cars rode with their small children in taxicabs at least monthly (n = 28), weekly (n = 27), or daily (n = 9), all without child restraints. Thirty-five of 50 states (70%) plus Washington, DC, exempt taxicabs from child restraint laws. Only 11 (27%) of 41 states with safety belt laws exempt taxicabs. There were 106 reported taxicab occupant fatalities from 1986 to 1990 in the United States, including 11 children and adolescents. National and state data on motor vehicle occupant morbidity do not separately examine taxicabs. Individual taxicab fleets we contacted would not release injury data. Of 50 urban taxicab fleets in four states (Delaware, Maryland, New Jersey, and Pennsylvania), only three (6%) offered child restraint devices by advance telephone request. There was no difference in availability based on state taxicab exemptions from child restraint laws. We conclude that taxicab use involving young children is common in this inner-city population. Data on taxicab occupant injuries are needed. Child restraint law exemptions for taxicabs should be eliminated. Education about, and enforcement of, child restraint laws for taxicabs is needed. Recent local legislation linking child restraint device availability to taxicab licensure should be encouraged. PMID- 8488805 TI - Infrared eye injury not due to radiant warmer use in premature neonates. AB - OBJECTIVE: Exposure to far-wavelength infrared radiation (lambda > 2000 nm) may cause corneal opacity, miosis, and delayed cataracts (onset > 30 days). Near wavelength infrared exposure (lambda < 1000 nm) may focus on the retina, causing burns; however, early eye examinations in neonates nursed under radiant warmers have failed to reveal acute injuries. Our purpose is to report long-term ophthalmologic outcome in infants treated under radiant warmers from birth. PARTICIPANTS AND METHODS: We report findings from eye examinations in infants followed up to a median age of 2 years, 9 months (range, 1 to 75 months), for (1) 33 infants nursed exclusively under radiant warmers for up to 5 days postnatally (mean [+/- SD] birth weight, 1.16 +/- 0.24 kg; mean gestation, 30 +/- 2 weeks) and (2) 14 convection-warmed incubator-nursed infants (1.26 +/- 0.22 kg, 31 +/- 2 weeks), who were slightly more mature. MAIN RESULTS: A trend toward retinopathy of prematurity was noted as occurring more frequently in the radiant warmer nursed infant population, and one infant in that group was blind. However, no macular burns and no permanent corneal, lens, or other anterior segment injuries were observed. CONCLUSION: Preliminary findings do not support permanent eye damage attributable to near- or far-wavelength infrared injury in neonates nursed under radiant warmers. PMID- 8488806 TI - Developmental outcome of preterm infants with transient neuromotor abnormalities. AB - OBJECTIVE: To determine the relationship between transiently abnormal neurologic findings in preterm infants and subsequent cognitive outcome at 4 years of age. DESIGN: Prospective 4-year follow-up. SETTING: Regional perinatal center in Syracuse, NY. PARTICIPANTS: One hundred thirty-one of 135 consecutively born infants of no more than 32 weeks of gestational age; 98% followed up from birth to 4 years of age. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Based on neuromotor evaluations performed at 6 and 15 months of age, two groups of infants were identified. One group had abnormal neurologic findings at 6 months of age that had resolved by 15 months of age (transiently abnormal group). The other group had normal neuromotor findings at both 6 and 15 months of age (normal group). The transiently abnormal group had significantly poorer scores on the Bayley Mental scale at 6 months of age (90 +/- 15 vs 108 +/- 10; P < .001), 15 months (91 +/- 21 vs 105 +/- 12; P < .001), and 24 months (91 +/- 19 vs 101 +/- 17; P < .001). However, at 4 years of age, cognitive performance on the McCarthy Scales was similar for the transiently abnormal and normal groups (General Cognitive index, 93 +/- 13 and 95 +/- 14, respectively). The incidence of poor cognitive outcome (Cognitive index < 84) decreased from 39% at 2 years of age to 18% at 4 years of age in the group with a history of transient neurologic abnormalities but remained unchanged (16% to 18%) in the normal group. CONCLUSION: Early neurologic abnormalities that are transient did not predict cognitive delays at 4 years of age in preterm infants. PMID- 8488807 TI - Unrecognized pertussis infection in adolescents. AB - Little information is available regarding the level of immunity to Bordetella pertussis among adolescents. We measured serum antibodies in 156 healthy adolescents to the following pertussis antigens: pertussis toxin, filamentous hemagglutinin, and 69-kd outer membrane protein. In an attempt to identify intercurrent pertussis infections, we also obtained a total of 43 repeated samples during the following 5 years. Using a 50% or greater rise in IgG enzyme linked immunosorbent assay titers to define seroconversion, we found an annual incidence of 6.1%; by alternative definitions of seropositivity, the predicted annual incidence of infection ranged from 1.2% to 8.2%. These data suggest that infection with B pertussis is common in the adolescent population. PMID- 8488808 TI - Black clouds. Work load, sleep, and resident reputation. AB - OBJECTIVE: Although it is assumed that residents in a specific training program will have comparable experiences, residents commonly perceive that some have consistently more difficult times on call. Such residents in our program are said to have "black clouds." We sought to determine if these perceptions were related to differences in real work load. METHODS: We collected data about the on-call experiences of our first-year pediatric residents (PL-1s) for 358 days (1355 on call experiences) during the 1984-1985 academic year. Every PL-1 (n = 19) reported the following data the morning after each night on call: hours of sleep, number of admissions, total number of patients, number of deaths, number of transfers to the pediatric intensive care unit, number of delivery room trips, and a subjective assessment of work load, using a three-point scale. The reputation of each house officer was determined by asking all residents in the program (PL-1s, PL-2s, and PL-3s) to rate each other three times during the year regarding how hard they worked on call. RESULTS: There were significant differences among PL-1s in how difficult they perceived their work load to be and in how much they slept (P < .001 using analysis of variance). However, actual work load (as measured by the number of either admissions or patients) did not vary significantly among the residents. There was a strong negative association between self-perception of work load and hours of sleep (r = -.75; 95% confidence interval, -0.73 to -0.76). Sleep was the major predictor of perceived work load (multiple R2 = .563 using multiple linear regression analysis). The absence of an association between perceived and actual work load is attributed to large differences in the residents' working styles. This is evidenced by a wide range of correlations among PL-1s between the number of admissions and hours of sleep (range of r values, -.66 to -.16). A reputation for difficult on-call experiences was strongly associated with few hours of sleep (r = -.77; 95% confidence interval, -0.49 to -0.91), but not with actual work load measured by the number of admissions, patients, deaths, or other variables. Sleep was the major predictor of reputation (multiple R2 = .567 using multiple linear regression analysis). CONCLUSIONS: Some residents did have a black cloud; they slept less, perceived that they worked harder than average, and had a reputation for having difficult on-call experiences. Residents with a black cloud function differently from their colleagues; for example, some may be inefficient, while others may create extra work for themselves. Residency program directors must recognize these functional differences to effectively evaluate and counsel house officers. PMID- 8488809 TI - Radiological case of the month. Amputated calcified ovary. PMID- 8488810 TI - Radiological case of the month. Pulmonary blastoma. PMID- 8488811 TI - Picture of the month. Anterior encephalocele. PMID- 8488812 TI - Pathological case of the month. Ovarian stromal hyperthecosis. PMID- 8488813 TI - Permanent vascular access: a nephrologist's view. AB - Vascular access complications are the greatest cause of morbidity in hemodialysis patients in the United States. Although arteriovenous fistulas have been recommended as the preferred mode of vascular access, recent data indicate that the majority of patients on hemodialysis in the United States have prosthetic graft fistulas. The most frequent complications of prosthetic graft fistulas are thrombosis and stenosis. Hospitalization rates for fistula complications are higher in patients with diabetes mellitus and of black race. Pathogenesis of intimal hyperplasia may include elaboration of platelet-derived growth factor and mechanical endothelial injury. Screening for stenosis and impaired blood flow in fistulas can be carried out with recirculation measurements, venous and intra access pressure measurements, and Doppler ultrasound. A combination of the techniques is probably the best current strategy for fistula screening and further evaluation. Surgical thrombectomy and fistula revision remain the standard for comparison of newer approaches to management of complications. Percutaneous angioplasty with or without stent placement, thrombolysis, and use of atherectomy devices may play an increasing role in the treatment of complications, although comparative trials of these modalities need to be performed. No satisfactory long-term pharmacologic means of preventing thrombosis, stenosis, or restenosis have been found for graft arteriovenous fistulas. It is hoped that future directions in the field of vascular access placement and management will include better strategies for allowing primary arteriovenous fistula development, advances in graft materials, improved understanding of the pathogenesis of thrombosis and stenosis, and development strategies to prevent complications. PMID- 8488814 TI - Angiotensin II modulates atrial natriuretic factor-induced natriuresis in cirrhosis with ascites. AB - Resistance to the natriuretic action of atrial natriuretic factor (ANF) in cirrhosis with ascites has been correlated with rising levels of antinatriuretic factors, such as renin, angiotensin II (AII), and aldosterone, as well as increased sympathetic nerve activity. To determine whether AII can serve as a mediator rather than only as a marker of the antinatriuresis, a nonpressor dose of AII (5 ng/kg/min) was given during an ANF infusion in eight patients with cirrhosis and ascites who responded to ANF infusion with a natriuresis. Patients were maintained in metabolic balance and measurements of para-aminohippuric acid, inulin, and lithium clearance were taken before and during infusion of ANF with or without AII. Atrial natriuretic factor infusion was associated with a natriuretic response accompanied by an increase in glomerular filtration rate, filtration fraction, and lithium clearance compared with baseline. The addition of AII was associated with a return of the glomerular filtration rate to baseline, with no change in filtration fraction. This was reversible on withdrawal of AII infusion. Natriuresis induced by ANF occurred despite baseline elevations of the renin angiotensin aldosterone system and was associated with an increase in distal delivery of sodium and a decrease in fractional reabsorption of distally delivered sodium as estimated by lithium clearance parameters. Angiotensin II infusion exerted effects on both proximal and distal nephron sites to abrogate ANF-induced natriuresis. These results suggest that AII may serve as a mediator as well as a marker of resistance to the natriuretic effect of ANF in patients with cirrhosis and ascites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488815 TI - The role of macrophages in diabetic glomerulosclerosis. AB - To elucidate the role of macrophages in diabetic glomerulosclerosis (DGS), an immunohistologic study was performed using monoclonal antibodies to common leukocyte antigen (DAKO-LC), T cells (T3), B cells (CD22), and macrophages (MAC 387, Leu-M5, and EBM-11). Kidney biopsy specimens were obtained from 28 patients with non-insulin-dependent diabetes mellitus. Cells were identified by a three layer immunoperoxidase technique applied to cold ethanol-fixed, paraffin-embedded sections and quantitated as the number of cells per glomerular cross-sections and number of cells per square millimeter of glomerulus. The severity of the diffuse lesions in each glomerulus was graded semiquantitatively. The average grades for all the glomeruli were calculated and registered as an index of DGS for a biopsy specimen. There was no relationship between the index of DGS and the number of T or B cells. However, the number of macrophages and common leukocyte-positive cells increased significantly in the moderate stage of glomerulosclerosis compared with the mild or advanced stage. The results suggest that macrophages may transiently infiltrate during the moderate stage of diffuse DGS, contributing to irreversible structural damage. PMID- 8488816 TI - Mesangial proliferative glomerulonephritis in southwestern American Indians. AB - A series of 166 American Indian renal biopsy specimens from 1971 to 1989 showed a very high proportion with mesangial proliferative glomerulonephritis with mesangial immunoglobulin deposition (Ig-pos mesGN). This disease comprised 68.7% of all the biopsies and 83.8% of all primary GN, proportions much greater than those (23.5% and 37.7%, respectively) of a local contemporaneous biopsy series from non-Indians (P < 0.001). These proportions and the extrapolated population based incidence rates of mesGN are the highest yet described in any population. Males and females were equally represented in the Indian Ig-pos mesGN series. Biopsy was most commonly performed in early adulthood, but duration of suspected disease prior to biopsy was often many years. Mesangial glomerulonephritis often occurred in family clusters. It was occasionally associated with rashes, arthralgias, and/or a history of alcohol abuse. Due to different surveillance and biopsy practices, the spectrum of severity was different in Zunis and Navajos, allowing examination of clinicopathologic correlations over a broad range of disease. Early disease was manifest by microscopic hematuria alone, but rates of severe disease, with hypertension, heavy proteinuria, and renal insufficiency, were very high. Clinical severity increased with age, with extension of pathology beyond the mesangium, and with scarring and vascular change. Changing patterns of deposition of mesangial immunoglobulin and of electron-dense deposits in sequential biopsy specimens, recurrence of disease in kidney transplants, and biopsy diagnosis of disease in asymptomatic relatives of afflicted subjects were all observed. Five-year renal failure rates were estimated at 41%, much higher than in most other series. This disease constituted most biopsied cases of GN-end stage renal disease in Navajos, and largely determined the young age of Navajo GN end stage renal disease subjects compared with their US-wide counterparts. To reconcile the diversity of clinical and morphologic findings in such homogeneous ethnic groups, and in individual families within such groups, we propose a unifying hypothesis for a broader spectrum of mesGN than traditionally defined by immunoglobulin subtype deposition. We also argue against a major role for IgA aggregates or immune complexes in initiating or propagating the mesangial inflammatory process, and propose that mesangial pathology of another, independent cause might be primary. Hyperinsulinemia, or insulin resistance, which is common in these populations and in other transitional populations with similar GN and ESRD patterns, might be one such mesangiopathic factor. PMID- 8488817 TI - Cyclophosphamide provides no additional benefit to steroid therapy in the treatment of idiopathic membranous nephropathy. AB - Thirty-six patients with idiopathic membranous nephropathy were retrospectively studied. The mean age was 47 years and the male to female ratio 25 to 11. Twenty eight patients (77.8%) had nephrotic syndrome at first investigation. Nineteen patients received corticosteroids alone (group A) and 17 received corticosteroids combined with cyclophosphamide (group B). The mean period of follow-up was 58.9 months (range, 12 to 156 months). The two groups did not differ in clinical or laboratory features at the time of biopsy or at the start of treatment. In the entire series a complete remission of proteinuria occurred in 13 of 36 patients (36.1%) and a partial remission occurred in 13 (36.1%); 10 patients (27.8%) had no response. Optimal remission of proteinuria was usually recorded 6 to 12 months after the start of treatment. The two groups showed no statistical differences regarding the rate of complete (seven v six patients; P = not significant) or partial (six v seven patients; P = not significant) remissions. Two patients (one from each group) entered end stage renal failure during follow-up. At last assessment, the number of patients with complete remission (four v three patients; P = not significant), nonnephrotic proteinuria (nine v nine patients; P = not significant), or nephrotic syndrome (five v four patients; P = not significant) was similar in both groups. In addition, final plasma creatinine did not differ significantly between the two groups (1.8 +/- 2.3 mg/dL v 2.6 +/- 2.6 mg/dL; P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488818 TI - Successful treatment of cystinuria with captopril. AB - Cystinuria is an autosomal recessive hereditary disorder associated with nephrolithiasis and its attendant complications. Traditional management aimed at increasing urinary cystine solubility using oral alkali, D-penicillamine, or mercaptopropionyglycine is often unsuccessful due to intolerable side effects. Two cystinuric patients intolerant of traditional therapy were treated with captopril for 1 year, resulting in a marked decline in urinary cystine excretion. Neither patient experienced recurrent nephrolithiasis or adverse drug effects. Captopril should be considered an alternative to traditional drug management of cystinuria. PMID- 8488819 TI - Acute continuous hemodiafiltration: a prospective study of 110 patients and a review of the literature. AB - One hundred ten critically ill patients with acute renal failure receiving acute continuous hemodiafiltration (ACHD) in our intensive care unit were studied prospectively. Acute continuous hemodiafiltration consisted either of continuous arteriovenous hemodiafiltration or of continuous veno-venous hemodiafiltration, and was used for 17,817 hours (mean duration of patient treatment, 161.9 hours), resulting in a fall from a mean pre-ACHD urea of 35.7 mmol/L to a plateau value of 16.8 mmol/L at 72 hours of treatment. The mean urea clearance achieved was 24.9 mL/min. Eighty of these patients (72.7%) were receiving artificial ventilation at the time of ACHD and 45 (40.9%) had more than four failing organs. The mean APACHE II score was 27.7. Despite the degree of illness severity, 42 patients (32.2%) survived to discharge from hospital. The use of ACHD was associated with hemodynamic stability, rapid normalization of electrolytes, and the ability to freely administer drugs, blood, and/or blood products. It also allowed for maintenance of an aggressive, nitrogen-rich, nutritional regimen. Support of these critically ill patients with acute renal failure using ACHD was achieved safely and without the employment of additional dialysis-trained nursing staff. Our own experience and a review of the available literature strongly suggest that the advantages associated with the use of ACHD therapies are clinically significant and support the view that ACHD is a modality of renal replacement most suited to critically ill patients with acute renal failure. PMID- 8488820 TI - Beta 2-microglobulin generation and removal in long slow and short fast hemodialysis. AB - We studied the influence of different modes of hemodialysis (HD) on plasma levels of beta 2-microglobulin (P-beta 2-m) and its correlation to changes in leukocyte count, complement activation (C3a), and elastase generation. The influence of dialyzer membrane, membrane surface area, duration of treatment, and blood flow was analyzed with respect to post-HD levels of P-beta 2-m. Twenty patients underwent 12 modes of bicarbonate hemodialysis in random order (n = 252) using three different membranes (Cuprophan [CU], hemophan [HE], or polyamide [PA], two dialyzer areas, and fast (400 mL/min) or slow (200 mL/min) blood flow (Qb) for 2 or 4 hours, respectively. All dialysate was collected and beta 2-m was analyzed (D-beta 2-m). After correction for hemoconcentration, P-beta 2-m concentrations were found to have decreased significantly during treatment with all three membranes (CU, 0.9 +/- 0.3 mg/L, P = 0.002; HE, 1.2 +/- 0.3 mg/L, P < 0.001; and PA, 8.3 +/- 0.3 mg/L, P < 0.001). Elimination of P-beta 2-m was influenced by type of membrane (P < 0.001) and ultrafiltration volume (P = 0.0019) but not by membrane area or Qb. The largest reduction in P-beta 2-m (-10.4 mg/L) was achieved by the following treatment combination: PA membrane, large dialyzer area, and low Qb for 4 hours. P-beta 2-m decreased more during PA dialysis at low Qb for 4 hours (-9.9 +/- 0.5 mg/L) than during high Qb for 2 hours (-6.8 +/- 0.5 mg/L, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488821 TI - The effects of recombinant human growth hormone and intradialytic parenteral nutrition in malnourished hemodialysis patients. AB - Malnutrition in hemodialysis patients is associated with increased morbidity and mortality. The use of intradialytic parenteral nutrition (IDPN) to improve nutritional parameters has been shown to be of limited benefit in most studies. We studied the use of recombinant human growth hormone (rHuGH) in potentiating the effects of IDPN in seven hemodialysis patients dialyzed with a Kt/V of 1.03 +/- 0.11 (mean +/- SEM), but with evidence of malnutrition: albumin, 3.2 +/- 0.18 g/dL; transferrin, 215 +/- 30 mg/dL; insulin-like growth factor-1 (IGF-1), 115 +/ 19 ng/mL, protein catabolic rate (PCR), 0.70 +/- 0.05 g/kg/d; and weight, 12.3% +/- 4.0% below ideal body weight. During 6 weeks of IDPN, resulting in an additional 18 +/- 4 kcal and 0.69 +/- 0.03 g of protein/kg body weight per dialysis session, albumin concentration increased to 3.5 +/- 0.14 g/dL (compared with baseline, P = NS), transferrin increased to 279 +/- 36 mg/dL (P < 0.002), IGF-1 increased to 152 +/- 32 ng/mL (P = NS), and PCR increased to 0.81 +/- 0.04 g/kg/d (P = NS). During the next 6 weeks, IDPN administration was continued and rHuGH, at a dose of 5 mg subcutaneously during each dialysis, was added to the regimen. This resulted in an increase in albumin concentration to 3.8 +/- 0.08 g/dL (P < or = 0.04 compared with end of IDPN phase), an increase in transferrin to 298 +/- 41 mg/dL (P = NS compared with end of IDPN phase), and an increase in IGF-1 to 212 +/- 45 ng/mL (P = 0.05 compared with end of IDPN phase).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488822 TI - Disseminated histoplasmosis with glomerulonephritis mimicking Wegener's granulomatosis. AB - Renal complications of disseminated histoplasmosis include chronic recurrent abcesses of the interstitium and urogenital tract. To our knowledge, glomerulonephritis has never been reported in histoplasmosis. We describe a case of proven histoplasmosis presenting with oral granulomatous ulceration and segmental glomerulonephritis that mimicked Wegener's granulomatosis (WG). All symptoms and renal parameters remitted under itraconazole treatment alone. In conclusion, glomerulonephritis may complicate the course of chronic disseminated histoplasmosis. Since it can masquerade as WG, systematic tissue staining for intracellular microorganisms should be done when WG is suspected. PMID- 8488823 TI - Glomerular disease and urinary Sezary cells in cutaneous T-cell lymphomas. AB - We report three cases of biopsy-documented renal glomerular disease occurring in patients with cutaneous T-cell lymphomas. One patient had immunoglobulin A (IgA) nephropathy and another had membranous nephropathy. The remaining patient had an immune complex glomerulonephritis without immunofluorescent evidence of IgA, but with mesangial deposits and a clinical course notable for stable renal function, minimal proteinuria, and episodic gross hematuria of renal origin. These three cases, along with IgA nephropathy in two of the four previously reported cases, suggest a possible association between cutaneous T-cell lymphoma and this glomerular lesion. In addition, Sezary cells were observed in the urine of two patients, one without evidence of glomerular disease. The prognostic value of this new observation is unknown. PMID- 8488824 TI - Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. AB - Two young human immunodeficiency virus (HIV)-infected patients, a 25-year-old woman and a 26-year-old man, consumed large amounts of germanium lactate citrate 18% as an "immunostimulant" for 9 months. The woman, who had stage II HIV infection, developed severe renal dysfunction (creatinine clearance, 7 mL/min/1.73 m2) and slight proteinuria (0.28 g/d) after ingesting 260 g germanium lactate citrate 18%. Hepatomegaly with liver dysfunction (SGOT, 102 U/L; gamma glutamyl transferase (GT), 159 U/L) and lactic acidosis (plasma lactate, 7.3 mmol/L) developed simultaneously. Renal biopsy revealed tubulointerstitial nephropathy with vacuolar cell degeneration and periodic acid-Schiff-positive intracellular deposits mainly in distal tubules. Liver biopsy disclosed severe hepatic steatosis; liver function tests returned to normal within 5 weeks. Since renal failure persisted for 2 years after ingestion of germanium (creatinine clearance, 14 mL/min/1.73 m2; proteinuria, 0.84 g/d), a second renal biopsy was performed, which showed marked but focal distal tubular atrophy and slight interstitial fibrosis. The male patient, who had stage III HIV infection, had ingested the same compound; he presented with a creatinine clearance of 43 mL/min/m2 and proteinuria of 0.36 g/d. Renal biopsy disclosed tubulointerstitial changes similar to those found in the female patient. After 9 months off germanium, creatinine clearance remained unchanged. Neutron activation analysis of all biopsy specimens in both cases documented germanium concentrations 10 to 70 times normal in renal tissue and 140 times normal in liver tissue. PMID- 8488825 TI - Papillary renal cell carcinoma with numeric changes of chromosomes in a long-term hemodialysis patient: a karyotype analysis. AB - A patient with renal neoplasm was nephrectomized 5 months after successful renal transplantation. The tumor was clearly diagnosed after renal transplantation, although a computed tomography scan before renal transplantation had suggested its presence. The patient had been on hemodialysis for 11 years, with extensive acquired renal cystic disease before renal transplantation. Pathology revealed a renal cell tumor with granular cells and tubulopapillary structure, consistent with papillary renal cell carcinoma. Karyotype analysis revealed that this tumor, which was 1.7 cm in diameter, showed trisomy of chromosomes 5, 16, and 20 and deletion of chromosome Y. This preliminary study suggests that cytogenetic changes of papillary renal cell tumor associated with acquired cystic disease are similar to those in the general population. PMID- 8488826 TI - Amplification of the arachidonic acid cascade: implications for pharmacologic intervention. AB - The signal transduction pathway that results in prostaglandin production is thought to occur in a stepwise manner that involves agonist-stimulated action of a phospholipase that releases the second messenger arachidonic acid from membrane phospholipids. Prostaglandin endoperoxide synthase (PGH synthase) then converts arachidonic acid to the prostaglandin precursors. Further delineation of this cascade has recently occurred with the identification of two distinct prostaglandin endoperoxide synthases, PGH synthase-1 and PGH synthase-2. There is evidence that PGH synthase-1 may have broad cellular expression and may be constitutively expressed in most cells. In contrast, PGH synthase-2 expression may be more limited and has been shown to be stimulated by a variety of cytokines and growth factors. Dexamethasone inhibits the expression of an early response gene, TIS10, which is homologous to PGH synthase-2. The exact mechanism of PGH synthase-2 gene regulation in mesangial cells is unknown; however, it may be a potential site for pharmacologic intervention. Regulation of PGH synthase-2 could in turn modulate prostaglandin production and temper the production of extracellular matrix and thus scar formation that occurs in a wide variety of inflammatory renal diseases. PMID- 8488827 TI - Adequacy of hemodialysis. PMID- 8488829 TI - Outbreak of hemodialysis-associated non-A, non-B hepatitis. PMID- 8488828 TI - Short-term responsiveness of membranous glomerulopathy to cyclosporine. PMID- 8488830 TI - Nonsyndromic cleft lip with or without cleft palate in west Bengal, India: evidence for an autosomal major locus. AB - Ninety extended families having one or more individuals affected with nonsyndromic cleft lip (CL) with or without cleft palate (CL/P) were ascertained in rural West Bengal, India. These families included 138 affected people, 64% of whom had CL alone and 66% of whom were male. Multiple-affected-member ("multiplex") pedigrees were less common than single-affected-member ("simplex") pedigrees, composing 34% of all extended pedigrees. There was no difference between multiplex and simplex pedigrees in the frequency of affected persons with CL alone, but multiplex pedigrees had a lower frequency of affected males (58%) than did simplex pedigrees (76%; P = .02). Complex segregation analysis using the POINTER computer program rejected both the hypothesis of no familial transmission (P < .0001) and the hypothesis that familiarity could be explained solely by a multifactorial/threshold model (P < .05). The hypothesis of major-locus inheritance alone could not be rejected. Among major-locus models examined, strictly recessive inheritance was rejected (P < .0001), but codominant and dominant models were not. Neither the addition of a multifactorial component nor the addition of a proportion of sporadic cases to the major-locus model improved the fit of the data. In conclusion, the results of complex segregation analysis were consistent with a dominant or codominant major-locus mode of inheritance of CL/P in these families. PMID- 8488831 TI - Concerns about the genetics of pre-eclampsia. PMID- 8488832 TI - Is the presence of two different Tay-Sachs disease mutations in a Cajun population an unexpected observation? PMID- 8488833 TI - A postulated mechanism for deletions with inversions. PMID- 8488834 TI - Insurance commissioners and genetic discrimination. PMID- 8488835 TI - Efficacy and applicability of interphase fluorescence in situ hybridization for prenatal diagnosis. PMID- 8488836 TI - Rapid prenatal diagnosis of chromosomal aneuploidies by fluorescence in situ hybridization: clinical experience with 4,500 specimens. AB - Detection of chromosome aneuploidies in uncultured amniocytes is possible using fluorescence in situ hybridization (FISH). We herein describe the results of the first clinical program which utilized FISH for the rapid detection of chromosome aneuploidies in uncultured amniocytes. FISH was performed on physician request, as an adjunct to cytogenetics in 4,500 patients. Region-specific DNA probes to chromosomes 13, 18, 21, X, and Y were used to determine ploidy by analysis of signal number in hybridized nuclei. A sample was considered to be euploid when all autosomal probes generated two hybridization signals and when a normal sex chromosome pattern was observed in greater than or equal to 80% of hybridized nuclei. A sample was considered to be aneuploid when greater than or equal to 70% of hybridized nuclei displayed the same abnormal hybridization pattern for a specific probe. Of the attempted analyses, 90.2% met these criteria and were reported as informative to referring physicians within 2 d of receipt. Based on these reporting parameters, the overall detection rate for aneuploidies was 73.3% (107/146), with an accuracy of informative results for aneuploidies of 93.9% (107/114). Compared to cytogenetics, the accuracy of all informative FISH results, euploid and aneuploid, was 99.8%, and the specificity was 99.9%. In those pregnancies where fetal abnormalities had been observed by ultrasound, referring physicians requested FISH plus cytogenetics at a significantly higher rate than they requested cytogenetics alone. The current prenatal FISH protocol is not designed to detect all chromosome abnormalities and should only be utilized as an adjunctive test to cytogenetics. This experience demonstrates that FISH can provide a rapid and accurate clinical method for prenatal identification of chromosome aneuploidies. PMID- 8488837 TI - Two-hit model for sporadic congenital anomalies in mice with the disorganization mutation. AB - Congenital anomalies have complex etiologies involving both genetic and nongenetic components. Many are sporadic, without obvious evidence for heritability. An important model for these anomalies is a mutation in laboratory mice that is called "disorganization" (Ds), which functions as a variable autosomal dominant and leads to a wide variety of congenital anomalies involving many developmental processes and systems. Variable expressivity, asymmetrical manifestations, and low penetrance suggest that somatic events determine the location and nature of these anomalies. A statistical analysis suggests that occurrence of anomalies in mice with the Ds mutation follows a Poisson distribution. These results suggest that congenital anomalies in mice with the Ds mutation occur independently of each other. We propose that Ds causes a heritable predisposition to congenital anomalies and that Ds and appropriate somatic events combine to compromise normal development. We also propose that some sporadic, nonheritable congenital anomalies involve somatic mutations at Ds-like loci. Ds may therefore serve not only as a model for developmental anomalies in cell fate and pattern formation but also for complex developmental traits showing variable expressivity, low penetrance, and sporadic occurrence in mice and humans. PMID- 8488838 TI - Neurobehavioral effects of the fragile X premutation in adult women: a controlled study. AB - Although previous studies have suggested that the fragile X premutation (fra [X] pM) does not cause deleterious effects, methodological constraints have prevented more definitive conclusions from being reached. In this report, we describe the neuropsychiatric and cognitive-neuropsychological status of 34 adult women with the fra (X) pM, as compared with a well-matched control group of 41 mothers of fra (X)-negative children with developmental disability. The results indicate that there are no meaningful differences between adult women with the fra (X) pM and control subjects with respect to cognitive abilities or profile, neuropsychological function, psychiatric diagnoses or symptoms, and self-rated personality profile. No measure for either group showed evidence of functioning outside the normal range except for a high lifetime prevalence of major depression in both groups. Additional exploratory analyses within the fra (X) group showed no significant effect of either the size of the fra (X) insert or X chromosome inactivation pattern in leukocytes, on any measure of neurobehavioral function. These findings provide additional information to professionals providing genetic counseling to, and assessment of, fra (X) families. PMID- 8488839 TI - Molecular analysis of the 18q- syndrome--and correlation with phenotype. AB - Seven individuals with deletions of the distal long arm of chromosome 18 were evaluated at the clinical, cytogenetic, and molecular levels. The patients had varying degrees of typical clinical findings associated with the 18q- syndrome. Cytogenetic analysis revealed deletions from 18q21.3 or 18q22.2 to qter. Somatic cell hybrids derived from the patients were molecularly characterized using ordered groups of probes isolated from a chromosome 18-specific library. In general, the size of the deletion could be correlated with the severity of the phenotype. Based on the clinical pictures of these seven patients, a preliminary phenotypic map for the clinical features associated with deletions of the distal portion of the long arm has been generated. Furthermore, genes previously localized to 18q21 were mapped relative to the chromosome breakpoints present in these patients. PMID- 8488840 TI - Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1. AB - Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCOF1 locus has been localized to chromosome 5q32-33.2. In the present study we have used the combined techniques of genetic linkage analysis and fluorescence in situ hybridization (FISH) to more accurately define the TCOF1 critical region. Cosmids IG90 and SPARC, which map to distal 5q, encompass two and one hypervariable microsatellite markers, respectively. The heterozygosity values of these three markers range from .72 to .81. Twenty-two unrelated TCOF1 families have been analyzed for linkage to these markers. There is strong evidence demonstrating linkage to all three markers, the strongest support for positive linkage being provided by haplotyping those markers at the locus encompassed by the cosmid IG90 (Zmax = 19.65; theta = .010). FISH to metaphase chromosomes and interphase nuclei established that IG90 lies centromeric to SPARC. This information combined with the data generated by genetic linkage analysis demonstrated that the TCOF1 locus is closely flanked proximally by IG90 and distally by SPARC. PMID- 8488841 TI - Incidence and origin of "null" alleles in the (AC)n microsatellite markers. AB - Twenty-three (AC)n repeat markers from chromosome 16 were typed in the parents of the 40 CEPH (Centre d'Etude du Polymorphisme Humain) families. Where parents were informative, the entire families were then typed. There were seven markers in which null alleles were demonstrated, as recognized by the apparent noninheritance, by a sib, of a parental allele. Four of these markers showed a null allele in a single sibship, while in the other three at least 30% of the CEPH sibships were shown to have a null allele segregating. One null allele was sequenced and shown to be the result of an 8-bp deletion occurring within the priming sequence for PCR amplification of the (AC)n repeats. In gene mapping or in application to diagnosis, the presence of a segregating null allele will not corrupt the linkage data but could result in loss of information. In isolated instances a segregating null allele may be interpreted as nonpaternity. The presence of a null allele may generate misleading data when individuals are haplotyped to determine the presence of linkage disequilibrium with a disease gene. PMID- 8488842 TI - Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism. AB - Acetylcholinesterase is present in innervated tissues, where its function is to terminate nerve impulse transmission. It is also found in the red blood cell membrane, where its function is unknown. We report the first genetic variant of human acetylcholinesterase and support the identity of acetylcholinesterase as the YT blood group antigen. DNA sequencing shows that the wild-type sequence of acetylcholinesterase with His322 (CAC) is the YT1 blood group antigen and that the rare variant of acetylcholinesterase with Asn322 (AAC) is the YT2 blood group antigen. Two additional point mutations in the acetylcholinesterase gene do not affect the amino acid sequence of the mature enzyme. PMID- 8488843 TI - Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: no cosegregation with severe hyperlipidemia. AB - Assessment of the apolipoprotein E (apoE) phenotype by isoelectric focusing of both hyperlipidemic and normolipidemic individuals identified five new variants. All mutations were confined to the downstream part of the APOE gene by using denaturing gradient gel electrophoresis (DGGE). Sequence analysis revealed five new mutations causing unique amino acid substitutions in the carboxyl-terminal part of the protein containing the putative lipid-binding domain. Three hyperlipoproteinemic probands were carriers of the APOE*2(Val236-->Glu) allele, the APOE*3(Cys112-->Arg; Arg251-->Gly) allele, or the APOE*1(Arg158-->Cys; Leu252 ->Glu) allele. DGGE of the region encoding the receptor-binding domain was useful for haplotyping the mutations at codons 112 and 158. Family studies failed to demonstrate cosegregation between the new mutations and severe hyperlipoproteinemia, although a number of carriers for the APOE*3(Cys112-->Arg; Arg251-->Gly) allele and the APOE*1(Arg158-->Cys; Leu252-->Glu) allele expressed hypertriglyceridemia and/or hypercholesterolemia. Two other mutant alleles, APOE*4-(Cys112-->Arg; Arg274-->His) and APOE*4+(Ser296-->Arg), were found in normolipidemic probands. The lack of cosegregation of these new mutations with severe hyperlipoproteinemia suggests that these mutations do not exert a dominant effect on the functioning of apoE. PMID- 8488844 TI - Ordering genes: controlling the decision-error probabilities. AB - Determination of the relative gene order on chromosomes is of critical importance in the construction of human gene maps. In this paper we develop a sequential algorithm for gene ordering. We start by comparing three sequential procedures to order three genes on the basis of Bayesian posterior probabilities, maximum likelihood ratio, and minimal recombinant class. In the second part of the paper we extend sequential procedure based on the posterior probabilities to the general case of g genes. We present a theorem that states that the predicted average probability of committing a decision error, associated with a Bayesian sequential procedure that accepts the hypothesis of a gene-order configuration with posterior probability equal to or greater than pi *, is smaller than 1 - pi *. This theorem holds irrespective of the number of genes, the genetic model, and the source of genetic information. The theorem is an extension of a classical result of Wald, concerning the sum of the actual and the nominal error probabilities in the sequential probability ratio test of two hypotheses. A stepwise strategy for ordering a large number of genes, with control over the decision-error probabilities, is discussed. An asymptotic approximation is provided, which facilitates the calculations with existing computer software for gene mapping, of the posterior probabilities of an order and the error probabilities. We illustrate with some simulations that the stepwise ordering is an efficient procedure. PMID- 8488845 TI - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood. AB - Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is a disorder of fatty acid catabolism, with autosomal recessive inheritance. The disease is characterized by episodic illness associated with potentially fatal hypoglycemia and has a relatively high frequency. A rapid and reliable method for the diagnosis of MCAD deficiency is highly desirable. Analysis of specific acylcarnitines was performed by isotope-dilution tandem mass spectrometry on plasma or whole blood samples from 62 patients with MCAD deficiency. Acylcarnitines were also analyzed in 42 unaffected relatives of patients with MCAD deficiency and in other groups of patients having elevated plasma C8 acylcarnitine, consisting of 32 receiving valproic acid, 9 receiving medium-chain triglyceride supplement, 4 having multiple acyl-coenzyme A dehydrogenase deficiency, and 8 others with various etiologies. Criteria for the unequivocal diagnosis of MCAD deficiency by acylcarnitine analysis are an elevated C8 acylcarnitine concentration (> 0.3 microM), a ratio of C8/C10 acylcarnitines of > 5, and lack of elevated species of chain length > C10. These criteria were not influenced by clinical state, carnitine treatment, or underlying genetic mutation, and no false-positive or false-negative results were obtained. The same criteria were also successfully applied to profiles from neonatal blood spots retrieved from the original Guthrie cards of eight patients. Diagnosis of MCAD deficiency can therefore be made reliably through the analysis of acylcarnitines in blood, including presymptomatic neonatal recognition. Tandem mass spectrometry is a convenient method for fast and accurate determination of all relevant acylcarnitine species. PMID- 8488846 TI - Segregation analysis of fat mass and other body composition measures derived from underwater weighing. AB - Segregation patterns of three body composition measures which were derived from underwater weighing were evaluated in a random sample of 176 French-Canadian families. Two of the variables can be considered as primary partitions of weight (fat mass [FM] and fat-free mass [FFM]), while the remaining variable (percent body fat [%BF]) is a derived index combining the measures of both fat and fat free weight. This study represents the first report investigating major gene effects for these measures. Segregation analyses revealed that a major locus hypothesis could not be rejected for two of the three phenotypes. The single exception was FFM, for which nearly 60% of the variance was accounted for by a non-Mendelian major effect, which may reflect environmentally based commingling or may be in part a function of gene-environment interactions or correlations. In contrast to the results for FFM, the results for each of FM and %BF were similar and suggested a major locus which accounted for 45% of the variance, with an additional 22%-26% due to a multifactorial component. Given the similarity of the major gene characteristics for these two phenotypes, the possibility that the same gene underlies both measures warrants investigation. A reasonable hypothesis is to consider genes that may influence nutrient partitioning, as the family of candidate genes to receive the major attention. PMID- 8488847 TI - Molecular topography of the secondary constriction region (qh) of human chromosome 9 with an unusual euchromatic band. AB - Heterochromatin confined to pericentromeric (c) and secondary constriction (qh) regions plays a major role in morphological variation of chromosome 9, because of its size and affinity for pericentric inversion. Consequently, pairing at pachytene may lead to some disturbances between homologous chromosomes having such extreme variations and may result in abnormalities involving bands adjacent to the qh region. We encountered such a case, where a G-positive band has originated de novo, suggesting a maternal origin from the chromosome 9 that has had a complete pericentric inversion. In previously reported cases, the presence of an extra G-positive band within the 9qh region has been familial, and in the majority of those cases it was not associated with any clinical consequences. Therefore, this anomaly has been referred to as a "rare" variant. The qh region consists of a mixture of various tandemly repeated DNA sequences, and routine banding techniques have failed to characterize the origin of this extra genetic material. By the chromosome in situ suppression hybridization technique using whole chromosome paint, the probe annealed with the extra G-band, suggesting a euchromatic origin from chromosome 9, presumably band p12. By the fluorescence in situ hybridization technique using alpha- and beta-satellite probes, the dicentric nature was further revealed, supporting the concept of unequal crossing over during maternal meiosis I, which could account for a duplication of the h region. The G-positive band most likely became genetically inert when it was sandwiched between two blocks of heterochromatin, resulting in a phenotypically normal child. Therefore, an earlier hypothesis, suggesting its origin from heterochromatin through so-called euchromatinization, is refuted here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488848 TI - Characterization of three de novo derivative chromosomes 16 by "reverse chromosome painting" and molecular analysis. AB - We have analyzed three de novo chromosome 16 rearrangements--two with a 16p+ chromosome and one a 16q+--none of which could be fully characterized by conventional cytogenetics. In each case, flow karyotypes have been produced, and the aberrant chromosome has been isolated by flow sorting. The origin of the additional material has been ascertained by amplifying and labeling the DNA of the abnormal chromosome by degenerate-oligonucleotide-primer-PCR and hybridizing it in situ to normal metaphase spreads (reverse chromosome painting). Both 16p+ chromosomes contain more than 30 Mb of DNA from the short arm of chromosome 9(9p21.2-pter), while the 16q+ contains approximately 9 Mb of DNA from 2q37. The breakpoints on chromosome 16 have been localized in each case; the two breakpoints on the short arm are at different points within the terminal band, 16p13.3. The breakpoint on the long arm of chromosome 16 is very close to (within 230 kb of) the 16q telomere. Determination of the regions of monosomy and trisomy allowed the observed phenotypes to be compared with other reported cases involving aneuploidy for these regions. PMID- 8488849 TI - Diverse growth hormone receptor gene mutations in Laron syndrome. AB - To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), we analyzed the growth hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. We amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). We identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71 + 1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, we determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations we identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. We conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas. PMID- 8488850 TI - Cardiovascular remodeling and its correction: toward a comprehensive strategy. PMID- 8488851 TI - Effects of peptide vasoconstrictors on vessel structure. AB - The peptide vasoconstrictors angiotensin II and endothelin-1, originally described as being derived exclusively from the plasma renin-angiotensin system and vascular endothelium, respectively, have been demonstrated to be produced independently of these sources. Local tissue angiotensin-generating systems are well documented and endothelin production has been demonstrated for a variety of nonendothelial cells, including vascular smooth muscle cells. There is increasing evidence that these locally produced vasoconstrictor peptides may contribute to blood vessel homeostasis, as well as the development of vascular pathologic conditions. Results obtained from pharmaceutical intervention in humans and animals of these systems strongly support this hypothesis. In addition to their vasoconstrictor properties, angiotensin II and endothelin-1 act as potent biologic effectors. In vitro, both vasoconstrictor peptides appear to modulate the activity of autocrine feedback loops in vascular smooth muscle cells. The activity of these feedback loops in vivo may represent a central mechanism for regulation and phenotypic differentiation of this cell type. The most well established autocrine feedback loops of vascular smooth muscle cells are constituted by platelet-derived growth factor and transforming growth factor beta, both of which are influenced by the action of angiotensin II and endothelin 1. The effects of the peptide vasoconstrictors on the (auto-) regulated feedback loops are of long-term structural importance, since both vasoconstrictors (via autocrine growth modulators) may influence the composition of the extracellular matrix of vascular smooth muscle cells. This includes effects on the synthesis and secretion of thrombospondin, fibronectin, tenascin, etc. The secretion of extracellular matrix glycoproteins themselves and incorporation into extracellular matrix in vitro appear to be linked to the activity of the autocrine feedback loops: e.g., stimulation of thrombospondin mRNA results in secretion of the glycoprotein only in the concomitant presence of exogenous platelet-derived growth factor, whereas the expression of fibronectin and tenascin may be directed by transforming growth factor-beta. The influence of angiotensin II and endothelin-1 on vascular smooth muscle cell surface receptor expression may represent a secondary mode of action of these vasoconstrictor peptides. Endothelin-1, for instance, can rapidly down-regulate platelet-derived growth factor-alpha receptor mRNA and both angiotensin II and endothelin-1, via induction of transforming growth factor-beta, may interrupt the platelet-derived growth factor based autocrine feedback loop. In vivo, the highly complex interactions between local and systemic vasoconstrictor production, autoregulated feedback loops, and extracellular matrix (which also serves as a reservoir for growth and differentiation modulators) are central to vessel homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8488852 TI - Control of vascular structure. AB - The development of the vasculature is a complex process, the end result making it possible for the cardiovascular system to supply each tissue with the required amount of blood at the correct pressure. The mechanisms controlling this development are poorly understood, but in general the changes seen appear to be adaptive, so that the vessels perform their tasks more effectively. Increasing flow appears to be a powerful stimulus to growth, resulting in an increased lumen, whereas raised mean pressure and pulse pressure are associated with an increased media:lumen ratio. Thus, the physical environment (intravascular flow and pressure) plays an important role in determining vascular structure. This suggests that an important aspect of future research will be to understand more closely the mechanism by which the physical factors can stimulate growth, a process that must presumably be mediated by proto-oncogenes. PMID- 8488853 TI - Hypertension as a risk factor syndrome: therapeutic implications. AB - Reduction of blood pressure as the only therapeutic goal of antihypertensive treatment may no longer be appropriate. High blood pressure is associated with an increased risk of cardiovascular events, but clinical trials of antihypertensive therapy have shown an inconsistent reduction in major cardiovascular endpoints. Importantly, the incidence of coronary artery disease has been reduced to only a small extent, suggesting that factors beyond high blood pressure are important in the genesis of atherosclerotic disease in hypertensive patients. It is evident, for example, that patients with hypertension have an exaggerated vulnerability to the consequences of lipid abnormalities. Moreover, it has recently been established that hypertension is characterized by insulin resistance and altered glucose tolerance. As a result, high plasma concentrations of insulin produce proliferative effects on vascular smooth muscle and connective tissue, and they may adversely affect the lipid profile. The left ventricle is also involved in hypertension, independent of blood pressure. There is growing evidence that there are increases in the muscle mass of the left ventricle and changes in its diastolic filling characteristics at very early stages of hypertension. The arterial circulation is similarly involved, for alterations in structure or function (reflected by diminished arterial compliance) can be demonstrated prior to the appearance of clinical hypertension. New therapeutic strategies should be aimed at the full spectrum of hypertension-related changes. Because the renin angiotensin system can contribute to the structural and functional cardiovascular characteristics of this condition, such agents as angiotensin-converting enzyme inhibitors may be especially effective in preventing or reversing these abnormalities and are emerging as a treatment of choice for hypertension. PMID- 8488854 TI - Some metabolic aspects of essential hypertension and its treatment. AB - We tested whether patients with essential hypertension (EH) have metabolic evidence of increased adrenergic activity, and if a relationship exists between carbohydrate metabolism and the blood pressure (BP) response to angiotensin converting enzyme (ACE) inhibition. Study 1 included 59 subjects who underwent resting ambulatory BP, heart rate, and resting energy expenditure (REE) measurement (by indirect calorimetry). REE was directly related to lean body mass (LBM) (r = 0.56, p < 0.0001) and to fasting plasma insulin levels (p < 0.03), after adjusting for LBM and age) but not to BP. The 38 subjects with EH had significantly higher fasting plasma insulin levels (54 +/- 4 vs 42 +/- 4 pM; p < 0.05) than the 21 normotensive subjects. When normalized by the LBM, the hypertensive patients had significantly higher REE values than the normotensive subjects (89 +/- 2 vs 78 +/- 3 J min-1.kg-1; p < 0.005). No differences in the other measured variables were found between the two groups. Thus, in this group of lean patients with stable EH, relative hyperinsulinemia is associated with a small increase in REE, the significance of which remains to be determined. In study 2, 20 patients with EH received an oral glucose tolerance test and a euglycemic insulin clamp before and after 3 months of treatment with cilazapril. Glucose-induced insulin response, but not insulin sensitivity, was improved by treatment in the whole group. Before therapy, the 12 responders (diastolic BP < 95 mm Hg) had similar glucose tolerance and insulin sensitivity to the eight nonresponders. Responders, however, had lower fractional potassium excretion than nonresponders both during fasting (9.6 +/- 1 vs 16.0 +/- 2.4%; p < 0.02) and during the glucose load (9.1 +/- 1.4 vs 13.1 +/- 1.1%; p < 0.04). In the responders, fasting potassium levels at baseline were directly related to the decrease in BP (p < 0.01) and to the improvement of glucose-induced insulin response (p < 0.04) achieved after treatment. Thus, the therapeutic effect of ACE inhibition is in part related to fractional potassium excretion, which, in turn, affects glucose tolerance through the influence of potassium levels on glucose induced insulin release. PMID- 8488855 TI - Organ blood flow protection in hypertension and congestive heart failure. AB - The nutrients to the different organs of the body are provided through the blood supply to these organs. Since the nutrient requirements change considerably and abruptly according to the demands set by, for example, physical activity, organ blood flow has to be adjusted accordingly. This is achieved by a complex interplay between neural (parasympathetic and sympathetic nerves), humoral (vasopressin, angiotensin, etc.), and local (ions, pH, adenosine, etc.) factors. It is also well recognized that diseases, such as hypertension and heart failure, as well as the drugs to treat them, can substantially affect organ blood flow. Using tracer microspheres, several studies in animals have shown that, during the established phase of hypertension, there is some decrease in cardiac output, which is then redistributed, with the brain, small intestines, and heart receiving a higher proportion. Blood flow to and vascular conductance in the other organs, particularly the kidneys, is decreased. Similar findings have also been observed in human hypertension. During congestive heart failure, most organs show a decrease in blood flow and there is a conspicuous increase in the sympathetic nerve activity. The drug responses may differ in the disease state and, from a clinical viewpoint, changes in some circulatory beds (e.g., cerebral, cardiac, renal, skeletal muscles) as well as the partition of blood flow into nutrient (tissue) and non-nutrient (arteriovenous anastomoses or shunts) parts can be of great importance. For example, overzealous antihypertensive therapy or the use of cerebral vasodilators may adversely affect cerebral circulation in certain situations and increased arterial blood flow may only be in the arteriovenous anastomotic part of the circulation. PMID- 8488856 TI - Pathobiology of restenosis after angioplasty. AB - Restenosis is a consequence of a disturbed wound healing process after the vascular trauma of angioplasty or similar intervention. Mechanisms involve clotting, cell recruitment and activation (from the blood, the vascular wall, and the perivascular tissue), as well as cell proliferation, matrix synthesis, and tissue contraction. In more than half of the lesions, these events are coordinated and self-limited, leading to a remodeling of the vessel wall with more stable and viable tissue than the original necrotic and lipid-laden atherosclerotic plaque. This remodeling may be as important as the gain in lumen for long-term patency. However, this basically favorable healing process may be disturbed by predominantly local conditions such as poor resulting wound anatomy, necrotic debris, excessive old plaque material, continued movement and irritation, or poor flow, leading to repetitive activation of any of these mechanisms. It is this unpredictable chronic persistence of these essentially physiologic mechanisms rather than the mechanisms themselves that eventually lead to an exuberant proliferative and synthetic response, which builds up restenotic mass together with thrombotic material and the old plaque components. PMID- 8488857 TI - Coronary blood flow in renovascular hypertension. AB - We assessed the acute effects of 2.5 mg oral cilazapril on systemic and coronary hemodynamics in seven renovascular hypertensive patients with a chronically overactive renin-angiotensin system (RAS), but with no electrocardiographic or echocardiographic signs of left ventricular hypertrophy. Cilazapril resulted in a significant decrease in mean arterial pressure and coronary vascular resistance, together with a prolonged increase in coronary sinus blood flow (CSBF). Post cilazapril handgrip resulted in larger increases in CSBF in response to a given increase in myocardial oxygen requirements. It is concluded that the chronic activation of the RAS exerts an adverse influence on the control mechanisms of CSBF and that converting enzyme inhibition reverses the effects of angiotensin II on coronary hemodynamics. Converting enzyme inhibitors may have a cardioprotective role in renovascular hypertension. PMID- 8488858 TI - Effect of cilazapril on isomyosin pattern in the spontaneously hypertensive rat. PMID- 8488859 TI - Renal pressure-natriuresis relationship. PMID- 8488860 TI - Effect of cilazapril on lipids. PMID- 8488861 TI - Modulation of sympathetic vasomotor control with cilazapril in mild hypertension. PMID- 8488862 TI - Diabetic microalbuminuria and cilazapril. PMID- 8488863 TI - Antihypertensive efficacy of cilazapril in general practice: assessment by ambulatory blood pressure monitoring. PMID- 8488864 TI - Effects of cilazapril on Na+ retention and ANP resistance in IDDM hypertensives. PMID- 8488865 TI - Comparative effects of cilazapril and atenolol on maximal and prolonged submaximal exercise performance in hypertensive males. PMID- 8488866 TI - Comparison of casual ambulatory and self-measured blood pressure in a long-term study with cilazapril and atenolol. PMID- 8488867 TI - New findings in short rib syndrome. AB - This white infant, born at 37 weeks of gestation, had a large cranium, bilateral anophthalmia, a midline cleft lip and palate, hypoplastic chest with short ribs, slightly protuberant abdomen, short limbs, bilateral single transverse palmar creases, a single umbilical artery, normal female external genitalia, normal (46 XY) chromosomes, and radiographic findings suggesting a short-rib (polydactyly) syndrome type IV (Beemer-Langer). Autopsy showed pulmonary hypoplasia, bilateral renal cystic dysplasia, intrahepatic bile duct cysts with periportal fibrosis, pancreatic cysts, absent internal genitalia, an atrophic optic chiasm, absent optic nerves, a single left anterior cerebral artery, polymicrogyria, and fusion of the frontal lobes, preoptic region, mammillary bodies, and thalami. PMID- 8488868 TI - Mixed gonadal dysgenesis: clinical, cytogenetic, endocrinological, and histopathological findings in 16 patients. AB - We describe clinical, cytogenetic, endocrine, and histopathological findings in 16 patients with mixed gonadal dysgenesis (MGD). All patients except 1 presented genital ambiguity and 10 of them had Ullrich-Turner manifestations. The 45,X/46,XY karyotype was the most frequent with a predominance of 45,X cells in both peripheral lymphocytes and gonads. In all cases Mullerian and Wolffian remnants and/or derivatives were found and in some patients both Wolffian- and Mullerian-derived structures were identified on the streak or testicular side. Postpubertal patients exhibited variable degrees of virilization and all of them had hypergonadotropism coexisting with low to normal baseline serum levels of testosterone; their testicular response to human chorionic gonadotropin (HCG) in terms of testosterone secretion was also variable, ranging from minimal to almost a normal response. All prepubertal patients but 1 had normal baseline levels of pituitary gonadotropins and testosterone and their gonadal response to the HCG challenge was highly variable. With the exception of 1 case, who had a 45,X/46,XY(p-) karyotype, no correlation between the cytogenetic data and degree of external genital ambiguity and the hormonal findings was observed. Additional information on the specific structural abnormalities involving the testis determining gene of the Y chromosome in patients with MGD is needed in order to further understand the mechanisms responsible for the wide variability characteristic of this disorder. PMID- 8488869 TI - Detection of the cystic fibrosis delta-F508 mutation at autopsy by site-directed mutagenesis. AB - In Caucasian populations cystic fibrosis (CF) is the most common autosomal recessive disorder. CF was previously considered rare in Mexico; however, the reported frequency is about 1% in autopsies. This discrepancy appears to be due to the inability to diagnose the illness during life. It is now known that in developing countries a great number of affected children die without the benefit of CF diagnosis and appropriate treatment. In this study we have used the PCR mediated site-directed mutagenesis technique for the detection of the delta-F508 mutation in a 6-month-old Mexican boy who died without definitive diagnosis. The tissue available from the child was a formaldehyde fixed paraffin-embedded liver. We identified the delta-F508 mutation in homozygous form in the propositus and in a heterozygous form in his parents. This represents the first report of CF molecular diagnosis in Mexico. PMID- 8488870 TI - Renal findings in 40 individuals with Williams syndrome. AB - We tabulated the frequency of renal abnormalities in 40 Williams syndrome individuals presenting for medical and/or developmental assessment to a multi disciplinary Williams syndrome program. The average age at time of assessment was 7 2/12 years. Seven individuals (7/40 = 18%) had abnormalities detected, including nephrocalcinosis = 2; marked asymmetry in kidney size = 2; small kidneys = 1; solitary kidney = 1; and pelvic kidney = 1. Renal function was also assessed. Two individuals had evidence of renal dysfunction, one secondary to nephrocalcinosis and the second due to hypercalcemia and interstitial nephritis of unclear pathogenesis. We examined the frequency of renal artery stenosis in 9 individuals who underwent abdominal angiography during cardiac catheterization. We found unilateral or bilateral mild renal artery narrowing in 4 individuals and normal renal arteries in the remaining 5. Persistent hypertension occurred in only 2 individuals and did not correlate with renal artery status. We conclude that intrinsic renal anomalies, as well as problems secondary to hypercalcemia, occur with sufficient frequency to warrant baseline renal screening in all individuals with Williams syndrome. PMID- 8488871 TI - Concordance and recessive inheritance of Leber congenital amaurosis. AB - Pedigrees were obtained on 43 patients with confirmed Leber congenital amaurosis, a rare form of blindness caused by congenital dysfunction of the retina. All of the pedigrees were consistent with autosomal recessive inheritance and the segregation frequency using classical segregation analysis was 0.24 +/- 0.07. Six of the 7 affected sib pairs were concordant in regards to systemic abnormalities. Despite previous reports that Leber congenital amaurosis can be inherited either as an autosomal dominant or recessive condition, our findings support only an autosomal recessive inheritance of this disorder. PMID- 8488872 TI - Apparent dominant transmission of the Rubinstein-Taybi syndrome. AB - The cause of the Rubinstein-Taybi syndrome (RTS), a multiple congenital anomalies/mental retardation (MCA/MR) syndrome first described in 1963, remains obscure. Recently, a deletion of chromosomal material at 16p13.3 has been found in some patients with the disorder, but no such deletion can be identified in the majority of affected individuals. Although the disorder has been well documented to be concordant in at least 7 monozygotic twin pairs and in one non-twin sib pair, only one clear-cut case of parent-to-child transmission has been reported previously. We present here a mother and daughter, both of whom appear to be affected with RTS, strongly suggesting either autosomal or X-linked dominant transmission. The paucity of previous cases of parent-to-child transmission may be related to either decreased fertility or decreased fitness in affected individuals. PMID- 8488873 TI - Molecular and cytogenetic characterization of 9p- abnormalities. AB - We report on 2 girls with terminal deletion of the short arm of chromosome 9 with concurrent duplication unrecognizable by routine chromosome studies. The phenotype of the patients was not specifically suggestive of the 9p-syndrome in the absence of trigonocephaly and long philtrum as cardinal manifestations. In addition to psychomotor retardation, their manifestations were mild and include upward slant of palpebral fissures and dolichomesophalangy which are characteristic of del(9p). Chromosome abnormalities were de novo in both cases. The two rearranged chromosomes 9 exhibit similar G-banding patterns and suggested the possible duplication of distal 7p. Fluorescence in situ hybridization (FISH) with a chromosome-7 specific library probe indeed identified that one derivative chromosome 9 was the result of a translocation between chromosomes 7 and 9 [der(9)t(7;9)(p15.3;p24] but failed to detect a signal on the other derivative 9. In the second case, the concurrent abnormality was an inverted duplication of proximal 9p and deletion of distal 9p [inv dup(9)(p13-->p22::p22-->qter)] confirmed by FISH using a chromosome 9 specific library probe. FISH clearly identified the origin of these 2 abnormal chromosomes 9 and provided crucial information for clinical evaluation. We emphasize the importance of utilizing updated cytogenetic and molecular techniques in the precise delineation of subtle or complex abnormalities where there are no useful phenotypic clues. PMID- 8488874 TI - Rubinstein-Taybi Syndrome with thymic hypoplasia. AB - We report the autopsy findings in a 20-month-old boy with Rubinstein-Taybi syndrome and DiGeorge sequence. No visible thymus was demonstrated at the time of autopsy. With careful microscopic examination, a few pieces of thymic tissues found near the thyroid gland showed remarkable depletion of both thymocytes and cortical epithelial cells. Immunohistological staining with T-cell surface antigens resulted in a definite positive reaction. Repeated respiratory infections present in this patient may, in part, be attributable to thymic hypoplasia. Other major anomalies included broad thumbs and great toes, microphthalmia, arrhinencephaly, patent ductus arteriosus, stenosis of the ureterovesicular junction, bilateral cryptorchidism, and minor facial anomalies. PMID- 8488875 TI - Cognitive and behavioral profile of the oculocerebrorenal syndrome of Lowe. AB - BACKGROUND: The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, cognitive impairment, and renal tubular dysfunction. Significant behavioral difficulties have been reported, but no formal study of intelligence or behavior has been described. METHODS: We surveyed IQ and behavior using archival data and standardized instruments in 47 affected males. RESULTS: Mean IQ was in the moderate mental retardation range (40 < or = IQ < or = 54), with 25% of tested individuals in the normal range (IQ > or = 70). The OCRL population was comparable to a normative population with mental retardation in language, communication, and socialization skills, but lower in independent living skills than means of either populations of individuals with mental retardation or visual impairment. Maladaptive behaviors, particularly stubbornness, temper tantrums, and stereotypic behaviors, were very frequent (> 80%). CONCLUSIONS: The diagnosis of OCRL is compatible with normal intelligence. Maladaptive behaviors significantly interfere with adaptive functions. These behaviors appear to define a characteristic behavioral phenotype in OCRL. PMID- 8488876 TI - Recombinant chromosome 9 possibly derived from breakage and reunion of sister chromatids within a paracentric inversion loop. AB - Chromosomally unbalanced offspring resulting from the recombination of parental paracentric inversions are uncommon. We report on a 20-month-old boy with a partial duplication of 9p due to the recombination of a paternal paracentric inversion. The patient's recombinant chromosome was designated rec(9)(p13- >p24::p12-->p24::p12-->qter). The patient's father and paternal aunt have a paracentric inversion of chromosome 9:inv(9)(p13p24). Although several mechanisms have been proposed to explain the chromosome imbalance generated from paracentric inversions, none of the previously described mechanisms can account for the structure of the recombinant chromosome observed in the propositus. We propose an unusual mechanism of formation involving breakage and unequal reunion of sister chromatids within the inversion loop to explain the structure of the patient's recombinant chromosome. PMID- 8488877 TI - In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy in a female fetus "suddenly at risk". AB - DNA methods to diagnose Duchenne muscular dystrophy (DMD) are not always informative, and we have published previously the first instance of in utero muscle biopsy to assess dystrophin in a male fetus having the same "X" as an affected sib. We present here a female fetus with a de novo X,1 translocation with breakpoint at Xp21, detected on amniocentesis for advanced maternal age. The translocation breakpoint placed her at high risk for DMD. In utero muscle biopsy at 20 weeks of gestation produced a specimen positive for dystrophin immunofluorescence indicating a likely normal fetus. The pregnancy was continued, and at term the baby girl was found to have normal serum creatine kinase levels, and was therefore unaffected with DMD. Our experiences add de novo Xp21 translocation to the indications for in utero muscle biopsy for diagnosis of DMD. PMID- 8488878 TI - Possible second case of tricho-oculo-dermo-vertebral (Alves) syndrome. AB - We report on a 10-year-old girl with trichodysplasia, onychodysplasia, hyperpigmented ichthyoform lesions on her shins, mild enamel dysplasia, and hyperkeratosis involving the soles. This combination of ectodermal defects has only been described by Alves et al. PMID- 8488879 TI - Living history-biography: from oral pathology to craniofacial genetics. PMID- 8488880 TI - Oral-facial-digital syndrome type I in a newborn male. AB - We report on a newborn male, born at term with clinical manifestations of oral facial-digital (OFD) syndrome type I. This syndrome is generally assumed to be inherited in an X-linked dominant fashion with lethality in males. Therefore, liveborn males are exceptional. This liveborn male also had Dandy-Walker malformation and polycystic kidneys. From a general point of view, distinction between the 8 types of OFD syndromes described so far appears subtle and considerable overlap exists between them. In this regard, it should be noted that polycystic kidneys different from adult polycystic kidney disease both macroscopically and microscopically are a frequent manifestation of OFD I. PMID- 8488881 TI - Case of (Y;1) familial translocation. AB - A balanced reciprocal translocation t(1;Y) (q11;q11) was found in an infertile man with severe oligoasthenospermia. The same translocation was found in his father. The role of X-chromosome inactivation during meiosis in a male carrying a Y;autosome translocation is discussed. PMID- 8488882 TI - Inguinal hernia and atrial septal defect in Tel Hashomer camptodactyly syndrome: report of a new case expanding the phenotypic spectrum of the disease. AB - We report on a girl with Tel Hashomer camptodactyly syndrome (THCS) born to first cousin parents. In addition to the usual findings, the patient had bilateral inguinal hernia and atrial septal defect, not previously described as component manifestations of the syndrome. The present description expands the phenotypic spectrum of the syndrome and gives new support to the hypothesized pleiotropic effects of the THCS gene on connective tissue. PMID- 8488883 TI - Short rib (polydactyly) syndrome type IV: Beemer-Langer syndrome. PMID- 8488884 TI - Clustering of cri du chat syndrome among the Bedouins. PMID- 8488885 TI - Mucinous cystadenoma of ovary in a patient with Williams syndrome. PMID- 8488886 TI - Poland anomaly with a limb body wall disruption defect. PMID- 8488887 TI - Inverted duplication involving alpha satellite DNA resulting in a C-negative-band in the qh region of chromosome 16. PMID- 8488888 TI - Monozygotic twinning and Wiedemann-Beckwith syndrome. PMID- 8488889 TI - The good ending. PMID- 8488890 TI - Trial volunteers sought. PMID- 8488891 TI - Motivating ourselves. PMID- 8488892 TI - Back stress solution. PMID- 8488893 TI - Back stress solutions. PMID- 8488894 TI - Nurses as house staff. PMID- 8488895 TI - Nurses as house staff. PMID- 8488896 TI - Pollution confusion. PMID- 8488897 TI - Spotting and treating spinal cord compression. PMID- 8488898 TI - Terminal weaning: a loved one's vigil. PMID- 8488899 TI - Visions of tomorrow's ICU. PMID- 8488900 TI - Treating bladder cancer: new methods, new management. PMID- 8488901 TI - Exploring the mystery of near-death experiences. PMID- 8488902 TI - The right way to culture a wound. PMID- 8488903 TI - What kind of recognition do staff nurses want? PMID- 8488904 TI - My name is nurse. PMID- 8488905 TI - Probing the safety of central venous catheters. PMID- 8488906 TI - Oncology nurses: doing the unexpected. PMID- 8488907 TI - How to aspirate fluid from small-bore feeding tubes. PMID- 8488908 TI - Effect of insulin therapy on progression of retinopathy in noninsulin-dependent diabetes mellitus. AB - In a six-month prospective study involving 60 noninsulin-dependent diabetics, we evaluated the effect of change to conventional insulin therapy on the pre existing retinopathy. Ten of 15 patients in group 1 (background or preproliferative diabetic retinopathy treated with insulin) compared to one of 15 patients in group 2 (background or preproliferative diabetic retinopathy treated with hypoglycemic agents) had progression of retinopathy. Worsening of retinopathy was related significantly only to the age of the patients (r = .752, P < .001). None of the 15 patients each in groups 3 and 4 (no retinopathy treated with insulin injections [group 3] or oral hypoglycemic agents [group 4]) developed retinopathy. PMID- 8488909 TI - A masked, randomized, dose-response study between cyclosporine A and G in the treatment of sight-threatening uveitis of noninfectious origin. AB - Thirty-two patients with sight-threatening uveitis and a decrease in visual acuity requiring systemic therapy were randomly assigned to either cyclosporine A or G in a dose-escalation study. Groups received from 2.5 mg/kg of body weight/day to 10 mg/kg of body weight/day of either drug along with low-dose prednisone. More patients taking cyclosporine G had improved visual acuity and a decrease in macular edema, which occurred more rapidly than in the other group, even at the lower doses tested. No difference in renal function was noted between groups at any doses tested. Four patients receiving cyclosporine G had hepatic alterations, but only one required cessation of the drug. The study indicates the potential usefulness of cyclosporine G, particularly at lower doses (4 mg/kg of body weight/day), which could lower the potential for serious renal complications. PMID- 8488910 TI - The effect of corneal thickness on applanation tonometry. AB - Simultaneous manometry and Perkins tonometry were performed at 10.0, 20.0, and 30.0 mm Hg on 15 eyes on which intraocular procedures were performed. There was a statistically significant relationship between corneal thickness and the error of Perkins tonometry. Thin corneas produced underestimations of the intraocular pressure by as much as 4.9 mm Hg, whereas thick corneas produced overestimations by as much as 6.8 mm Hg. Measuring the corneal thickness is necessary to interpret properly the results of Goldmann applanation tonometry, particularly in eyes with thin corneas. PMID- 8488911 TI - A clinicopathologic correlative study of noncontact transscleral Nd:YAG cyclophotocoagulation. AB - We studied the histopathologic changes of three eyes enucleated two weeks, eight weeks, and 17 months, respectively, after noncontact Nd:YAG cyclophotocoagulation. The histologic findings at two weeks were destruction of the nonpigmented and pigmented ciliary body epithelium, occlusion of the capillaries of the ciliary processes, and ciliary body stromal necrosis in the region of the processes. Hyperplasia of the pigmented and nonpigmented epithelium, fibrosis and near total atrophy of the ciliary processes, and partial atrophy of the ciliary muscles were present at eight weeks and 17 months. We concluded that application of treatment 1.0 to 1.5 mm posterior to the corneoscleral limbus selectively destroys the pars plicata, and that, histologically, the mechanism for reducing intraocular pressure appears to be destruction of ciliary processes with reduction of aqueous formation. PMID- 8488912 TI - Long-term visual outcome of ocular hypotension after thermosclerostomy. AB - Maximum intraocular pressure reduction is often the goal of glaucoma filtering procedures. To evaluate whether surgically induced ocular hypotension adversely affects visual acuity, we reviewed the visual outcome of 87 eyes of 67 patients who had undergone thermosclerostomy with follow-up of at least two years. Final visual acuity was compared in three groups on the basis of postoperative intraocular pressure level (< or = 10.0 mm Hg; > 10.0 mm Hg and < or = 21.0 mm Hg; and eyes that did not consistently fit solely in either group [mixed]). Average loss in visual acuity measured 1.8 +/- 3.0, 2.2 +/- 2.9, and 1.2 +/- 2.1 Snellen lines, respectively (P = .542). These data suggest that hypotensive eyes are not at greater risk for visual loss after glaucoma filtering procedures compared to normotensive eyes. PMID- 8488913 TI - Calcium channel blockers in the management of low-tension and open-angle glaucoma. AB - Fifty-six patients with either open-angle or low-tension glaucoma who were concurrently taking calcium channel blockers were compared to similar groups not taking such medications for a mean follow-up period of 3.4 years. Serial stereoscopic optic nerve photographs and visual fields of all patients were evaluated for evidence of glaucomatous progression. In patients with low-tension glaucoma, there was a significant difference in the progression of visual field defects, with only two of 18 eyes (11%) of patients taking calcium channel blockers, compared to ten of 18 eyes (56%) of controls showing new visual field defects. Similarly, low-tension glaucoma patients taking calcium channel blocker therapy demonstrated no evidence of progressive optic nerve damage, compared to eight of 18 control eyes (44%). In contrast, patients with open-angle glaucoma taking calcium channel blockers showed no marked difference in the progression of glaucoma, compared to controls. These findings suggest that calcium channel blockers may be useful in the management of low-tension glaucoma. PMID- 8488914 TI - The influence of patient-related variables in the timing of cataract extraction. AB - Data from a prospective study of quality of life after cataract extraction with intraocular lens implantation were used to examine associations between patient factors and the timing of cataract extraction. The 495 patients were drawn from 76 ophthalmologists' offices in three cities. Patients were categorized as waiting three months or less or four months or more to schedule their operations after their physicians' recommendations. Patients who delayed scheduling their operations were more likely to be younger, have higher incomes, be working full time, have higher life satisfaction, have lower levels of depression and higher levels of vigor, have had a less than perfect previous operation, have lower scores for mid-range vision and higher scores for cataract symptoms, be fearful of nighttime driving, and be heavy drinkers. Conversely, patients who delayed their operations were less likely to be covered by Medicare and to expect excellent postoperative vision and a short recovery time. A discriminant analysis correctly classified 68.9% of the patients according to timing group. PMID- 8488915 TI - The penetration of oral ciprofloxacin into the aqueous humor, vitreous, and subretinal fluid of humans. AB - We examined ciprofloxacin levels in the aqueous humor, vitreous, or subretinal fluid in 40 patients undergoing cataract extraction, vitrectomy, or scleral buckling. Ciprofloxacin, 750 mg, was administered orally an average of 17 1/2 and 5 1/2 hours preoperatively. We obtained mean ciprofloxacin levels of 0.53 microgram/ml in aqueous humor, 0.51 microgram/ml in vitreous, and 0.71 microgram/ml in subretinal fluid. These vitreous levels exceed the minimum inhibitory concentration (MIC)90 of Staphylococcus epidermidis, Propionibacterium species, Pseudomonas aeruginosa, Proteus mirabilis, and Haemophilus influenzae, as well as the MIC70 of S. aureus and Bacillus cereus. Therefore, ciprofloxacin may have a role in the management and prevention of endophthalmitis. PMID- 8488916 TI - Effect of eye patching on ocular surface. AB - We studied the effect of pressure patching in 27 medical students. Fourteen students had pressure patching in one eye (group 1) and 13 (group 2) had light patching. The fellow eye of each volunteer remained unpatched (group 3). Clinical signs and symptoms were scored and evaluated at the first and the following (after overnight) examinations. Before patching no subject had any of the clinical signs or symptoms. After the patch was removed in groups 1 and 2, all except one volunteer in each group had clinical signs or symptoms, or both, whereas in group 3, none had clinical signs or symptoms. Group 1 had greater scores for clinical signs (P = .019) and for symptoms (P = .038) as compared to group 2. In group 1, two participants did not complete the study period (by removal of the patch) because of severe discomfort and three had temporary irregularities in corneal surface with temporary decrease of vision. We suggest that pressure patching may cause discomfort and changes in visual acuity that are usually attributed to other reasons. PMID- 8488917 TI - Excimer laser keratectomy after radial keratotomy. AB - Radial keratotomy to treat myopia has been characterized by a lack of predictability. Until recently, patients with undercorrected myopia who were unsatisfied with their visual outcome could only be offered secondary augmentation procedures, which were equally unpredictable. We performed excimer laser keratectomy in six eyes of five patients whose myopia was undercorrected after radial keratotomy. The average residual spherical equivalent refractive error after radial keratotomy was -2.40 diopters, and this was reduced to -0.48 diopters after laser treatment. Final uncorrected visual acuity ranged from 20/80 to 20/20, and visual acuity was corrected to within one line of the preoperative best-corrected value in all patients. Epithelialization of all eyes occurred within four to six days. There were no incidences of corneal neovascularization, including no vascularization of the radial keratotomy incisions. Our findings suggest excimer phototherapeutic keratectomy offers a safe and more controlled method of augmenting undercorrected myopia after radial keratotomy. PMID- 8488918 TI - Eosinophil granule major basic protein deposition in corneal ulcers associated with vernal keratoconjunctivitis. AB - An indirect immunofluorescence assay detected eosinophil granule major basic protein in the inflammatory debris covering deepithelialized cornea in two patients with vernal keratoconjunctivitis. A slight degree of non-specific fluorescence was present in the control autopsy corneas. High concentrations of the eosinophil granule major basic protein inhibit epithelial migration and protein synthesis, whereas low concentrations affect epithelial migration. The results suggest participation of eosinophil granule major basic protein in the ulcerative process. PMID- 8488919 TI - Transesophageal echocardiography in the diagnosis of branch retinal artery obstruction. AB - We examined a 28-year-old man and a 19-year-old woman with branch retinal artery obstruction. Both were examined exhaustively. In each patient, a patent foramen ovale was demonstrated by transesophageal echocardiography after a transthoracic study disclosed no abnormalities. These observations suggest that transesophageal echocardiography is valuable in examining young patients with retinal emboli in whom cardiac abnormalities are suspected. PMID- 8488920 TI - Longitudinal study of the early electroretinographic changes in Alstrom's syndrome. AB - We obtained serial electroretinograms in four patients aged between 6 months and 5 years with Alstrom's syndrome and studied the early stages of the severe retinopathy that is characteristic of that disease. The weak electroretinographic signals found at age 6 months demonstrate a severe early cone dysfunction; one year later the cone activity is undetectable. The rod component of the electroretinogram is initially normal but can rapidly deteriorate to become undetectable as early as 5 years of age. These unusual electroretinographic findings are pathognomonic of Alstrom's syndrome and different from other cone rod dystrophies or other syndromes with similar phenotypes such as Bardet-Biedl, Laurence-Moon, and Cohen syndromes. PMID- 8488922 TI - Transpupillary continuous suture for intraoperative mydriasis. PMID- 8488921 TI - The outgrowth of lens epithelial cells onto the anterior capsule after intraocular lens implantation. PMID- 8488923 TI - Subcutaneous emphysema of the eyelids after dacryocystorhinostomy. PMID- 8488924 TI - Comparison of time required for strabismus correction by using the microscope or loupes. PMID- 8488925 TI - Ophthalmic manifestations of the chromosome 11q deletion syndrome. PMID- 8488927 TI - Massive spontaneous subretinal hemorrhage from a choroidal metastasis. PMID- 8488926 TI - Endophthalmitis caused by beta-lactamase-positive Moraxella nonliquefaciens. PMID- 8488928 TI - Echographic signs of perfluorodecalin. PMID- 8488929 TI - Determination of corneal image-forming properties from corneal topography. PMID- 8488930 TI - A biometric study of ocular changes during accommodation. PMID- 8488931 TI - Causes of reduced visual acuity on long-term follow-up after cataract extraction in patients with uveitis and juvenile rheumatoid arthritis. PMID- 8488932 TI - The influence of exposure duration in transscleral Nd:YAG laser cyclophotocoagulation. PMID- 8488933 TI - Recession of both horizontal recti muscles in Duane's retraction syndrome with elevation and depression of the adducted eye. PMID- 8488934 TI - Vogt-Koyanagi-Harada syndrome in patients with Cherokee Indian ancestry. PMID- 8488935 TI - The surgeon as gatekeeper. AB - The author pays tribute to three deceased members of the North Pacific Surgical Association who directed his own career. The gatekeeper function of surgical specialists is discussed, and surgeons are urged to become more active in this role. Increased involvement in managed care planning and cost control, particularly in smaller communities, is encouraged. PMID- 8488936 TI - Role of computed tomographic scans in the staging of esophageal and proximal gastric malignancies. AB - In order to determine the accuracy of computed tomographic (CT) scanning, CT scan results were compared with operative and pathologic findings in 45 patients with esophageal and proximal gastric malignancies. CT scans were evaluated with respect to nodal metastases, hepatic metastases, and adjacent spread. Eight patients did not undergo surgery because of advanced disease noted on the CT scan. Of the remaining 37 patients, sensitivity of CT for all 3 parameters was less than 60%, whereas the specificity was greater than 90%. The positive predictive value was greater than 90% for nodal metastases and adjacent spread and 67% for hepatic metastases. The negative predictive value was less than 40% for nodal metastases and adjacent spread and 90% for hepatic metastases. For esophageal and proximal gastric malignancies, CT is useful in identifying advanced disease and in predicting resectability. In less advanced cases, CT is not sensitive, and its negative predictive value is poor with regard to local and lymphatic spread. CT scanning is useful to stage the most advanced cases but because of limited accuracy should be combined with other diagnostic studies when accurate staging is required. PMID- 8488937 TI - Diagnosis and management of stage IE and stage IIE gastric lymphomas. AB - We performed a retrospective study involving 56 patients with stage IE or stage IIE gastric lymphomas treated between January 1980 and January 1990. Endoscopy had a sensitivity of 98% compared with 83% for radiographic contrast studies. The data were analyzed with respect to 10 prognostic factors. Age greater than 65 years and an elevated lactate dehydrogenase level were associated with a significantly lower 5-year survival rate (each p = 0.001). Those patients having had gastric resection with grossly negative margins demonstrated improved survival compared with those patients who did not have complete resection (67% versus 29%). The use or omission of radiotherapy had no effect on survivorship (51% versus 55%). Neither tumor size, stage, sex, site of extragastric involvement, time from onset of symptoms to diagnosis, nor microscopic resection margins influenced survival. We conclude that endoscopy with biopsy is the diagnostic procedure of choice for gastric lymphoma. Gastric resection still plays an important role in the management of stage IE and stage IIE gastric lymphomas, whereas chemotherapy remains the mainstay of therapy. The role of radiotherapy remains undefined. PMID- 8488938 TI - Critical appraisal of the angiographic portacaval shunt (TIPS). AB - The transjugular intrahepatic portacaval shunt (TIPS) is a novel angiographic method for achieving portal decompression without operation. Fifty-nine consecutive patients underwent a total of 80 consecutive TIPS procedures. The procedure was unsuccessful in 4 patients (7%) and initially succeeded in 55 (93%). Eighteen patients (30%) underwent 2 or more TIPS procedures during the same hospitalization due to technical difficulties, early rebleeding, shunt stenosis, or thrombosis. Early TIPS occlusion occurred in seven patients (12%) and led to recurrent variceal hemorrhage in five. Forty-two percent of the cases of persisting or recurrent bleeding were nonvariceal. Procedure-related complications occurred in 10% of TIPS procedures or 14% of patients. Twenty-three patients (39%) were actively bleeding at the time of the procedure, and, in 6 of these (26%), bleeding was never controlled. In-hospital mortality (25%) was related only to the presence of bleeding at the time of TIPS (56% for emergent versus 5.5% for non-emergent, p < 0.0001). Mortality was not related to the Child Pugh classification. Hemodynamic stabilization, vasoconstrictor therapy, balloon tamponade, and sclerotherapy were underutilized in 30% to 40% of patients prior to TIPS. Aggressive medical management should be used to stop variceal hemorrhage prior to TIPS in all patients, regardless of the Child-Pugh classification. Prospective trials comparing TIPS with sclerotherapy and surgical shunt are required to demonstrate the proper role of this procedure in the management of portal hypertension and variceal hemorrhage. PMID- 8488939 TI - Extending the limits of lung cancer resection. AB - Patients with locally advanced bronchogenic carcinoma are often considered to have unresectable disease because of invasion into vital structures, or they undergo resection with questionable or involved margins, which results in local recurrence later. Brachytherapy (direct application of radioactive sources to the tumor bed) offers the potential to provide tumoricidal doses of radiation to the target area with minimal toxicity to surrounding structures. In this study, one of two different techniques of brachytherapy was utilized to treat 15 highly selected patients with histologically positive (n = 8) or suspicious (n = 7) margins after resection. The techniques were easy to apply and were not associated with any complications directly related to their use. One postoperative death resulted from a perforated peptic ulcer. In the remaining 14 patients, at a mean follow-up of 38 months, local control was complete in 12 (86%) patients, and 8 patients are alive, with 7 free of disease. Thoracic brachytherapy may offer the potential for cure to patients whose disease would otherwise be considered inoperable. PMID- 8488940 TI - Effects of age and severity of illness on outcome and length of stay in geriatric surgical patients. AB - From April 1, 1990, to March 31, 1992, 8,899 patients who were 65 years of age and older underwent an anesthetic and surgical procedure in a 1,000-bed community hospital in Victoria, British Columbia, Canada. The hospital has been using a proprietary system called MedisGroups for assessing the severity of illness on admission and in-hospital morbidity. All patients were followed up until death or discharge from the hospital. Using the hospital database, we analyzed the patient sample to test the hypothesis that severity of illness was more important than age in predicting postoperative morbidity and mortality rates. Using correlation and multiple regression analysis, we found that the severity of illness was a much better predictor of outcome than age. The results were significant at the level of p < 0.001. Based on the results of this study, we recommend that age not be used in surgical decisions in the elderly. PMID- 8488941 TI - Endoscopic retrograde cholangiopancreatography after laparoscopic cholecystectomy. AB - We assessed the use of endoscopic retrograde cholangiopancreatography (ERCP) after laparoscopic cholecystectomy (LC) at our hepatobiliary referral center. This assessment included patients from outside institutions with post-LC problems. Between May 1990 and September 1992, we performed 522 LCs and 1,723 ERCP examinations. There were 78 patients who underwent 143 ERCP examinations after LC, 65% of whom were referred. ERCP findings were categorized as follows: normal results (8%), problems inherent to stone disease (65%), and iatrogenic injury (27%). The types of inherent problems were common bile duct (CBD) stones, pancreatitis, and papillary stenosis/microlithiasis. Within the CBD stone group, 5 of 26 patients also had papillary stenosis, and, within the pancreatitis group, 9 of 11 patients also had papillary stenosis, making papillary stenosis the most frequent observation (55%). Almost all of these patients (96%) required endoscopic papillotomy for successful treatment. The iatrogenic injury group was comprised of 21 patients, 16% of whom had cystic duct leak and 84% of whom had CBD injury. These patients required a variety of endoscopic procedures including endoscopic papillotomy (67%), CBD endoscopic stenting (76%), percutaneous drainage of biloma (29%), and percutaneous transhepatic biliary drainage (24%). Open surgical procedures after endoscopic assessment or treatment were required in only three patients in the iatrogenic group and in none in the inherent group. At this time, long-term follow-up is not possible with regard to biliary stricture. We conclude that the majority of problems after LC are either due to papillary stenosis/microlithiasis with or without CBD stones or to biliary injury. Both can be successfully diagnosed and treated with endoscopic techniques. PMID- 8488942 TI - Clinical results of cryopreserved valved conduits in the pulmonary ventricle-to pulmonary artery position. AB - Aortic valved homograft conduits (AVHC) have become valuable in the pulmonary ventricle (PV)-to-main pulmonary artery (MPA) reconstruction in congenital heart defects. Since 1985, 45 patients, ranging in age from 12 days to 32 years, underwent PV-to-MPA reconstruction utilizing cryopreserved AVHC. Operative deaths included seven patients (16%), six of whom died as a result of the complexity of their underlying heart defects. One late death (2%) occurred as a result of infective endocarditis 48 months after conduit placement. The 38 patients who survived the operation remained in the intensive care unit for a mean of 5.7 +/- 1.0 days (median: 4 days; range: 2 to 37 days). The mean hospital stay was 13.0 +/- 1.8 days (median: 9 days; range: 6 to 63 days). The mean follow-up was 40.0 +/- 3.6 months (median: 40 months; range: 10 months to 7.1 years). Only two patients (5%) required reoperation for conduit stenosis with systolic pressure gradients of 60 to 80 mm Hg at 10 and 14 months, respectively, after operation, and both reoperations were successful. During outpatient visits, 16 patients are totally asymptomatic, and 21 patients have minimal symptoms (New York Heart Association class II). Only 10 patients (26%) require digoxin, and 2 patients (5%) need diuretics as part of their medical regimen. Recent echocardiographic examinations show insignificant pressure gradients in all 37 currently surviving patients. Thus, barring operative mortality, which is almost always associated with the nature of the underlying heart defect, the use of cryopreserved AVHC is a safe and effective alternative for PV-to-MPA reconstruction. PMID- 8488943 TI - Use of thoracoscopy in clinical practice. AB - Endoscopic surgery and, in particular, thoracoscopy, have become useful clinical tools as both technique and instrumentation have evolved. Our experience with a series of 20 patients undergoing thoracoscopy, including the indications, results, and outcome, is presented. Indications for thoracoscopy and biopsy or resection include the diagnosis and, in some cases, treatment of idiopathic pulmonary infiltrates, mycetomas, lung masses, spontaneous pneumothorax, and empyema. Morbidity is limited, and there has been no mortality due to the procedure. PMID- 8488944 TI - Simplified preperitoneal Marlex hernia repair. AB - The routine use of mesh for repair of inguinal hernia has been popularized by Lichtenstein and others. Although preperitoneal placement is more appealing than the onlay technique, the classical approach by Nyhus and Condon is difficult under local anesthesia and denervates the inguinal muscles to some degree. Preperitoneal mesh may become the standard for inguinal hernia as the laparoscopic approach becomes more popular. This report describes the author's first 100 hernia repairs done using a simplified preperitoneal approach under local anesthesia. The preperitoneal space is entered directly through the posterior floor, but a complete covering of the direct, indirect, and femoral spaces is accomplished similar to an open technique. After placement of the mesh, a truly "tension-free" closure of the posterior floor can be accomplished. Patients are discharged home in 1 to 2 hours. Because a standard approach and block are used, the learning curve for this operation should be brief compared with that of the laparoscopic method. The follow-up of this series is short (average: 15 months), but there have been no recurrences or infections. One patient returned to the operating room within 4 hours due to an arterial bleeder in Scarpa's fascia but was discharged that day and had no subsequent problems. Another patient has a postoperative neuralgia probably unrelated to the mesh. Otherwise, there has no complications with the placement of the Marlex mesh. Patients are allowed to return to full activity and work at their discretion. PMID- 8488945 TI - Diagnosis and staging of pancreatic adenocarcinoma with dynamic computed tomography. AB - We assessed the accuracy of dynamic contrast-enhanced computed tomography (CT) in the diagnosis and staging of 213 patients with pancreatic carcinoma and compared it with the accuracy of angiography and surgery. A correct CT diagnosis of pancreatic carcinoma was made in 207 of 213 (97%) patients. Tumors were located in the pancreatic head in 64%, the body in 22%, and the tail in 10%, and enlarged the pancreas diffusely in 4%. CT staged 25 (12%) patients as having potentially resectable tumors and 188 (88%) as having unresectable tumors on the basis of local extension (72%), contiguous organ invasion (43%), vascular invasion (82%), and distant metastases (50%). Compared with angiography in 60 patients, CT detected vascular invasion missed on angiography in 20%, and angiography detected invasion missed by CT in 5%. In these latter cases, other CT criteria of unresectability were present, and angiography provided no significant staging information. Compared with surgery in 71 patients, CT accurately predicted unresectable tumors in 100% of patients and resectable tumors in 72% of patients. Eleven of the patients with CT-resectable tumors underwent resection. Median survival was 22.7 months, with four patients alive at a median of 15.5 months postoperatively. Palliative resections were performed in six patients, and median survival was 14.4 months. PMID- 8488946 TI - Surgical management of the post-phlebitic leg syndrome. AB - Twenty-five patients (32 limbs) with severe retrograde ejection venous syndrome (post-phlebitic leg syndrome) were surgically treated from 1971 to 1986 using a "very complete fasciotomy" with or without other individualized procedures. Clinical data, venographic findings, operative choices, and outcome were analyzed retrospectively. The theoretic benefit of adopting this new and conceptually accurate diagnostic label and the principle of "no incompetent perforators, no ulcers" is discussed. The patients generally had been managed for 10 to 20 years with conservative neglect or operative inadequacy. With correct conceptual understanding, anatomic stratification, defined indications for surgery, and individualization of procedures, an excellent result has been obtained with a low rate of serious complications. The very complete fasciotomy should be suitable for general use in treating this difficult and controversial syndrome. PMID- 8488947 TI - Review of the pathologic diagnoses of 2,216 appendectomy specimens. AB - A retrospective review of 2,216 patients surgically treated for a clinical diagnosis of acute appendicitis was performed. In 80% of cases, histologic acute appendicitis was found; 57% of these patients were male. The rate of normal appendectomy was 16%, and females comprised 68% of that group. The remaining 102 cases (4%) were designated as the alternate diagnosis group. Apart from histologic diagnoses that could be considered variants of normal (57) or acute inflammation (20), the alternate diagnosis group included such entities as neoplasm, parasitic infection, mucocele, and diverticulitis. PMID- 8488948 TI - Evaluation of 50 consecutive segmental hepatic resections. AB - The development of increasingly sensitive imaging techniques along with improved follow-up and screening of high-risk patients has led to hepatic tumors, both primary and secondary, being detected while still at an early stage. Improved understanding of hepatic anatomy along with advances in surgical technique has led to the ability to undertake hepatic resections based on the segmental hepatic anatomy as described by Couinaud. The purpose of this paper is to assess the safety, technique, and oncologic efficacy of segmental hepatic resection. Fifty consecutive patients undergoing segmental hepatic resection during a 3-year time period ending in January 1992 were reviewed. Parametric statistical analysis was undertaken using Student's t-tests. Overall mortality was 2% with a morbidity rate of 8%. Transfusion requirements were 1 +/- 1.5 U; however, cirrhotic patients showed a significantly increased transfusion requirement of 2.0 +/- 1.3 U versus 0.7 +/- 1.3 U (p = 0.03). Sixty percent of patients required no transfusion at all. The mean duration of inflow occlusion was 42 +/- 17 minutes. Resection margins were clear of tumor by greater than 1 cm in 48 of 50 patients. Segmental hepatic resection is a safe and effective technique that occasionally may offer advantages over formal resection. Some aspects of the technique are reviewed. PMID- 8488949 TI - Laparoscopic cholecystectomy in pregnancy. AB - It has been stated that pregnancy is an absolute contraindication to laparoscopic cholecystectomy. After failed medical management, five gravid patients underwent successful laparoscopic cholecystectomy with single-film intraoperative cholangiography. One patient was in the first trimester, three were in the second trimester, and one was in the third trimester. All carried the pregnancy to term and delivered normal children. Laparoscopic cholecystectomy can be safely performed during pregnancy and offers the potential of significant cost savings compared with traditional medical management of cholecystitis complicating pregnancy. PMID- 8488950 TI - Double aortic arch causing tracheoesophageal compression. AB - Since 1972, 17 patients have been surgically treated for double aortic arch at our institution. The procedure became necessary before 12 months of age in 11 patients and before 24 months in 16 patients. The major symptoms were respiratory distress, noisy breathing, and respiratory infections; four patients also had dysphagia. A high degree of clinical suspicion should warrant further investigation. Barium swallow and bronchoscopy were diagnostic and revealed extrinsic compression of the esophagus and trachea, respectively. Division of the anterior arch was performed in 16 patients; the right (posterior) arch was divided in the remaining patient. Kommerell's diverticulum was found in four patients and was resected in order to avoid recurrence of dysphagia by compression. A vascular suspension procedure was necessary in 13 patients to further release the trachea and esophagus. There was no mortality in this series, and symptomatic improvement was achieved in all patients. A degree of tracheomalacia may be responsible for some residual symptoms in four patients. PMID- 8488951 TI - Fate of infected and eroded hemodialysis grafts and autogenous fistulas. AB - Between 1970 and 1991, we placed 1,090 grafts (bovine and polytetrafluoroethylene) in 1,041 patients and created 1,034 autogenous fistulas in 856 patients for hemodialysis. Subsequent revisions for complications resulted in a total of 3,944 operations performed in patients with grafts and 1,633 operations in patients with autogenous fistulas. A total of 255 infections developed in 158 of the patients with grafts, whereas 8 infections developed in 7 patients with autogenous fistulas. The puncture infection rate was 5%/yr (12%/yr for a second puncture infection). The clean wound infection rate was 3% for grafts and 0.4% for autogenous fistulas. We made an attempt to salvage the graft, usually with a segmental bypass, in 75% of patients with a graft infection. Grafts were salvaged in 80% of patients in whom salvage was attempted (60% of all patients with an infection). The results in the few patients with infected autogenous fistulas were relatively poor. PMID- 8488952 TI - Diagnosis and management of pericardial abscess in trauma patients. AB - Pericardial infection is an uncommon clinical entity after traumatic injury. Although invasive intervention is rarely necessary for mild pericardial inflammation, pericardial abscess can be life-threatening. The charts of 27 patients with pericarditis requiring management in the intensive care unit and/or invasive intervention at Harborview Medical Center during a 10-year period were reviewed. Six cases of trauma-related pericarditis were identified, including three cases of pericardial abscess following torso trauma without initial cardiac or pericardial injury. Pericardial abscess following trauma was associated with the sepsis syndrome and multiple system organ failure (MSOF) in all patients. Computed tomography and pericardiocentesis were useful diagnostic adjuncts. All patients required thoracotomy for pericardial drainage and pericardiectomy. Successful surgical management of pericardial abscess contributed to the resolution of sepsis, multiple end-organ dysfunction and, ultimately, patient survival in all cases. We conclude that pericardial abscess, although rare, should be considered a potential occult site of sepsis capable of driving MSOF in trauma patients. Expedient diagnosis and surgical drainage are essential for successful patient outcome. PMID- 8488953 TI - Lethal nature of ischemic gastropathy. AB - Gastropathy on the basis of mesenteric arterial ischemia can be masked in presentation as the typically more benign entities of gastritis, gastric ulceration, or gastric atony. Gastritis and ulceration are commonly associated with stress, hyperacidity, Helicobacter pylori infection, or medication injury. Gastric atony is less commonly seen and usually attributable to diabetes mellitus, vagotomy, or mechanical gastric outlet obstruction. Gastric ischemia as a cause of gastropathy is an underappreciated phenomenon with a particularly poor prognosis in which early diagnosis is essential to potentially successful intervention. Seven patients with ischemic gastropathy are described; all are women, aged 41 to 71 years, smokers, with hypertension. Nausea, vomiting, weight loss, and gastrointestinal bleeding were the common presenting symptoms. All patients had endoscopic or autopsy-proven gastric ulcerations or necrosis, and two patients had proven gastroparesis. Four of five patients with ischemic gastritis died within 3 months of diagnosis despite vascular reconstruction. The two patients with gastroparesis underwent aorto-celiac bypass and are well 9 and 20 months, respectively, after operation. Treatment results were distressingly unsatisfactory, especially in those patients in whom gastritis rather than gastroparesis was the presenting problem. Although the high mortality of mesenteric ischemia is well described, little documentation of gastric ischemia exists in the literature. This entity is generally not considered in the differential diagnosis of gastritis, ulceration, or gastroparesis. Empirically, an early diagnosis and treatment may improve the survival in this select patient group. PMID- 8488954 TI - Does the use of erythropoietin in hemodialysis patients increase dialysis graft thrombosis rates? AB - Erythropoietin (EPO) is highly efficacious in the treatment of the anemia of chronic renal failure. Evidence for a reported serious side effect, increased dialysis graft thrombosis, is equivocal. Sixty-four hemodialysis patients utilizing polytetrafluoroethylene (PTFE) grafts were treated with EPO. The patients served as their own historical controls. There were 1.188 thrombectomies and 0.222 mechanical problems per 1,000 patient-days prior to the initiation of EPO treatment. With EPO, the values were 0.656 and 0.222, respectively. Patients were separated into low-, medium-, and high-dose EPO groups and analyzed within groups for the effect of EPO and between groups for a dose-dependent response. According to an analysis of variance procedure, there was no statistically significant differences between the groups, which suggests that EPO is not thrombogenic to dialysis grafts. PMID- 8488955 TI - DRD2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations. AB - We defined interpopulation differences in the frequency of the dopamine D2 receptor DRD2/Taq1 A1 allele, which has previously been associated with alcoholism. Frequencies of the A1 allele in unrelated subjects were 0.18 to 0.20 (se = 0.02 to 0.03) in several Caucasian populations previously assessed, 0.38 (+/- 0.05) in American Blacks (n = 44), 0.63 (+/- 0.07) in Jemez Pueblo Indians (n = 23), and 0.80 (+/- 0.04) in Cheyenne Indians (n = 52). The existence of large interpopulation differences in the frequency of the Taq1 alleles suggests that associations to disease status could readily be generated or masked if disease and control groups were uneven in ethnic composition. To address the possibility that the 4-fold higher frequency of the A1 allele in Cheyenne Indians was related to an increased vulnerability to alcoholism in that population, 47 Cheyenne Indians were psychiatrically interviewed and blind-rated. However, there was no significant difference between interviewed controls (0.73 +/- 0.06, n = 24), subjects with alcoholism and/or drug abuse (0.74 +/- 0.06, n = 23) and noninterviewed population controls (0.87 +/- 0.05, n = 20). Legitimate association of the DRD2/Taq1 allele to alcoholism would presumably require it to be in linkage disequilibrium (nonrandom association) with a functional mutation at DRD2 or elsewhere. The level of disequilibrium would vary between populations and could place an upper bound on the strength of an association.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488956 TI - Neuropsychological deficits are correlated with frontal hypometabolism in positron emission tomography studies of older alcoholic patients. AB - In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488957 TI - Measurement of acute tolerance to alcohol in human subjects. AB - Acute tolerance can be defined as a decrease in response to alcohol within a single exposure to the drug, which occurs independently of changes in blood alcohol concentrations (BACs). BACs change over time in most human alcohol administration studies, and computational techniques that account for these changes must be used to measure the rate of acute tolerance development. The most widely used acute tolerance measure in human research is often called the Mellanby effect, and involves the comparison of responses at the same BAC on the ascending and descending limbs of the blood alcohol curve. We compared the Mellanby measure with two other measures of acute tolerance: a conceptually similar area under the curve measure, and a slope function approach that used data only from the descending limb of the blood alcohol curve. The measures were intercorrelated and discussed with regard to empirical and conceptual issues. Exploratory comparisons of those with and without a family history of alcoholism are reported. Methodological recommendations for the computation of acute tolerance are made. The results suggest new methods for measuring the rate of acquisition of acute tolerance, and suggest areas for future research on tolerance-proneness and risk for alcoholism. PMID- 8488958 TI - What triggers the resolution of alcohol problems without treatment. AB - This study investigated natural recoveries (self-change) from alcohol problems, and overcame several methodological problems that affected the few previous studies of this phenomenon. Three groups of individuals who had resolved an alcohol problem without treatment were interviewed about their drinking history, life events that occurred during the year prior to their resolution, and factors that helped maintain their resolution. As a control for prevalence of life events, a control group of nonresolved, nontreated alcohol abusers were interviewed about events in a randomly selected year. Collaterals were interviewed for all subjects. No life event or constellation of events was differentially associated with the resolutions across the three resolved groups or differentiated the resolved and nonresolved groups. Interviews with resolved subjects were qualitatively analyzed-the majority (57%) of recoveries were characterized as involving a "cognitive evaluation" or appraisal of the pros and cons of drinking. Spousal support was reported by the greatest number of resolved subjects as having helped them maintain their resolution. Findings from this study may provide direction for developing new treatment strategies and for accelerating self-change among problem drinkers in the community. The study also demonstrates the importance of using a control group, without which very different conclusions might have been drawn. PMID- 8488959 TI - CDT by anion-exchange chromatography followed by RIA as a marker of heavy drinking among men. AB - Carbohydrate-deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population-based study examined the diagnostic value of CDT among consecutive middle-aged males including 122 social drinkers (mean alcohol consumption 88 +/- 79 g per week) and 77 non-alcoholic heavy drinkers (301 +/- 195 g/wk). Ninety-six men with a well-documented history of chronic alcoholism (> or = 1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pI = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean +/- SD = 14 +/- 5 U/I) were significantly lower than those of heavy drinkers (19 +/- 13 U/I, p < 0.01) and alcoholics (34 +/- 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption (r = 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non-alcoholic heavy drinkers. PMID- 8488961 TI - Alcoholic beverage licensing practices in California: a study of a regulatory agency. AB - A mail survey sent to all 25 State of California Alcoholic Beverage Control (ABC) offices and distributed to all 167 investigators assessed investigators' decisions to recommend issuance or denial of alcoholic beverage license applications. Investigators responded to three hypothetical vignettes that involved applications for liquor licenses. Findings show that although ABC investigators are influenced by public protests, illegal applications, and an applicant's moral character, they consistently favor licensing the applicant. The two formal rules that were designed specifically to respond to the community's welfare do not present serious barriers to obtaining an alcohol license. As a state regulatory organization, ABC is influenced greatly by the industry that it is supposed to regulate. PMID- 8488960 TI - Effect of haloperidol on measures of craving and impaired control in alcoholic subjects. AB - We recently proposed that alcoholics suffer from a functional defect within the basal ganglia/limbic striatum or its modulation by dopaminergic projections from the ventral tegmentum, and that inhibition of striatal output caused by the prodopaminergic effects of alcohol ingestion induces or exacerbates craving and impaired control over alcohol consumption in alcoholic individuals. To test this hypothesis, 16 subjects with a diagnosis of alcohol dependence or abuse were studied in a double-blind, placebo-controlled experiment in which the effects of the D-2 antagonist haloperidol on measures of craving and impaired control were assessed before and after administration of a priming dose of alcohol. Subjects were pretreated with 0.015-0.025 mg/kg haloperidol (experimental condition) or 2 ml normal saline (control condition), and subsequently consumed 0.4-0.6 g/kg ethanol as their preferred alcohol-containing beverage. Significant increases in subjectively rated craving for alcohol and perceived difficulty resisting additional alcohol consumption occurred following the priming dose of alcohol when subjects were pretreated with saline. In contrast, no significant changes in reported ability to resist additional alcohol occurred when subjects were pretreated with haloperidol, and reported levels of craving decreased relative to baseline following haloperidol pretreatment. Subjects also consumed about 25% less optionally available alcohol when pretreated with haloperidol than when pretreated with saline. These findings support the hypothesis that craving and impaired control are induced or exacerbated by the prodopaminergic effects of alcohol consumption. PMID- 8488962 TI - Serum carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with chronic liver diseases. AB - We measured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employees, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcoholic liver cirrhosis, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 +/- 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 +/- 5.1 and 13.7 +/- 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics. PMID- 8488963 TI - Alcohol-related mortality in Spain. AB - Alcohol-related mortality and years of potential life lost in Spain in 1986 have been studied according to the official statistics with regard to the population mortality in our country. 6.1% of the deaths in Spain in 1986 were related to alcohol consumption, mainly caused by malignant neoplasm (26.0%), digestive diseases (23.6%), and unintentional injuries (21.1%). Mean potential years of life lost for alcohol-related deaths until 65 was 7.3. Unintentional injuries were responsible for the greater part (61.2%) of alcohol-related years of potential life lost. The present study shows the high mortality rate associated with alcohol consumption in our country, as well as its importance in premature death. PMID- 8488964 TI - Effect of bedtime ethanol on total inspiratory resistance and respiratory drive in normal nonsnoring men. AB - We have previously reported that bedtime ethanol (2.0 ml/kg of 100 proof vodka) increases upper airway closing pressure in males who habitually snored but were otherwise healthy. We also observed that some of these snorers developed obstructive apneas. To explore this phenomenon in more detail, we measured the inspiratory resistance (RI) and respiratory drive after bedtime ethanol in 10 nonobese men (ages 23 to 33) with no history of snoring. Subjects went to bed wearing a tightly fitting valved mask over the nose and mouth that allowed measurement of inspiratory and expiratory flow, pressure in the mask, and endtidal CO2. We measured RI by calculating the pressure difference between the mouth and a balloon positioned in the midesophagus. Respiratory drive was quantified by the inspiratory occlusion pressure (P0.1), the ventilatory response to hyperoxic hypercapnia (delta VE/delta PETCO2), and the ventilatory response to isocapnic hypoxia (delta VE/delta SaO2). Measurements were made during waking and during stage 2 NREM sleep on two nights: (1) when the subjects drank 1.5 ml/kg of 100 proof vodka in orange juice over a 30-min period 15-45 min before lights out and (2) when the orange juice contained less than 0.1 ml of vodka floating on the top. Eight of the nine men in whom we had technically adequate measurements showed a rise in RI during NREM sleep above the waking level on both control and ethanol nights and the sleeping RI was greater on the ethanol than on the control night.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488965 TI - A genetic familial study of monoamine oxidase B activity and concentration in alcoholics. AB - Platelet monoamine oxidase B (MAO B) activity and concentration were studied in a small sample of alcoholic families (n = 8) and in 20 unrelated, nonalcoholic controls. Complex segregation analyses of familial data indicated that both activity and concentration are controlled by a single major gene locus with a multifactorial background effect accounting for 0-50% of the variance. When the alcoholic family members (n = 24) were compared with the controls, all determinations of activity display significant differences, whereas MAO B concentration levels showed no difference. These results indicated that the lowered MAO B activities frequently reported among alcoholics do not reflect a change in the number of MAO B macromolecules expressed in platelets, but could be caused by the presence of an inhibitor or by a polymorphic or variant form of the enzyme. PMID- 8488966 TI - Urinary level of L-fucose as a marker of alcoholic liver disease. AB - The urinary levels of L-fucose were measured in 93 alcoholics; 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease (p < 0.001). The urinary L-fucose level was also significantly higher (p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 +/- 97 vs. 240 +/- 95 mumol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 +/- 29 vs. 155 +/- 60 mumol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 +/- 97 mumol/g of creatinine) than with viral cirrhosis (265 +/- 42 mumol/g of creatinine) (p < 0.001). The measurement of urinary L fucose may be a useful marker of alcoholic liver disease. PMID- 8488967 TI - MAST scores, alcohol consumption, and gynecological symptoms in endometriosis patients. AB - Alcohol consumption (quantity, frequency, and pattern) and alcohol-related problems were determined in endometriosis patients (n = 137), patients with other gynecological disorders (n = 91), and normal control subjects (n = 98). Participants completed a self-administered questionnaire, including the Michigan Alcoholism Screening Test (MAST), questions to determine the quantity and frequency of alcohol use, and questions regarding the relationship between gynecological symptoms and alcohol intake. The percentage of endometriosis patients with MAST scores greater than five or seven was significantly greater than that of normal control subjects (p = 0.045 and p = 0.009, respectively), but did not differ from that for patients with other gynecological disorders. Endometriosis patients with high MAST scores (> or = 5) tended to consume more alcohol on a yearly basis than normal control subjects with high MAST scores (p = 0.07). Among participants who experienced gynecological symptoms and were not abstainers, 31% of endometriosis patients, 9.5% of normal control subjects, and 14.3% of patients with other gynecological disorders reported increasing their alcohol consumption when experiencing gynecological symptoms. Endometriosis patients tended to differ in this regard from normal control subjects (p = 0.058) and were significantly different from patients with other gynecological disorders (p = 0.039). The evidence suggests that the gynecological problems of endometriosis may be a major medical correlative of alcoholism in women. PMID- 8488968 TI - Immune function in alcoholism: a controlled study. AB - Several studies have shown an increased risk for infection and cancer in alcoholic patients. The mechanisms for such observations remain largely unknown. In an effort to investigate the possibility of immunological dysfunction in alcoholism, we studied three immune parameters in 47 hospitalized chronic alcoholic patients and 47 age- and sex-matched normal controls. The immune measures were: (1) lymphocyte phenotyping, with estimates of percentages of T cells, B cells, T helpers, T suppressors, natural killer (NK) cells, and cells carrying the activation markers IL2R1 and I2; (2) NK cell activity; and (3) lymphokine-activated killer cell activity. Results indicate a significant increase in the IL2R and I2 lymphocyte markers in alcoholic patients compared with matched controls. We also found a nonsignificant trend for a decrease in the percentage of suppressor T cells in the alcoholic group, as well as a trend for a negative correlation between the percentage of T suppressor cells and age. There were no significant differences in either NK or lymphokine-activated killer cell activities between the two groups. Furthermore, there were no significant associations between duration and intensity of alcohol consumption and any of the immune measures. These results suggest subtle alterations in immune regulation in alcoholic patients that cannot be explained solely on the basis of duration and/or amount of alcohol consumed. PMID- 8488969 TI - A time series analysis of the impact of the alcohol warning label on antenatal drinking. AB - In a sample of over 12,000 African-American gravidas, we tested the hypothesis that the Federal Beverage Labeling Act of 1988 has decreased antenatal drinking. Results of time series analysis indicated a 7-month lag in the impact of the alcohol warning label. Controlling for population changes, antenatal drinking began to fall as of June 1990. However, this decrease was small in size and did not impact on the heaviest drinkers. Seasonal trends in drinking were also detected, with peaks around the end of the year and the summer. PMID- 8488970 TI - Drinking patterns and correlates of drinking among pregnant teenagers. AB - Many adolescents drink, and the rate of teenage pregnancy is increasing, yet the effect of drinking among pregnant teenagers has received little attention. We present a description of the drinking patterns of 124 pregnant teenagers attending a prenatal clinic in Pittsburgh. Sixty-nine percent of the women were African-American, and the average age was 16 years (range 13-18 years). Eighty two percent drank the year before pregnancy, while 54%, 19%, and 15% drank during the first, second, and third trimesters, respectively. All substance use decreased between the first and third trimesters, with the exception of tobacco, which rose significantly. Binge drinking (5+ drinks/occasion) occurred in 31% of the sample before pregnancy, rose to 35% in the first trimester, and then fell precipitously. Binge drinkers during pregnancy were more likely to be white and heavier users of tobacco, marijuana, and cocaine. Binge drinkers experienced alcohol and tobacco use and sexual intercourse earlier than nonbinge drinkers. Binge drinking in the first trimester may be considered a risk factor for infants of adolescents. PMID- 8488971 TI - Secondary immune response to hepatitis B virus vaccine in alcoholics. AB - The efficacy of full vaccination against hepatitis B virus (i.e., including the 1 year booster injection) was evaluated in 28 alcoholic patients with minimal liver disease. Although such patients are reportedly poor responders, the proportion of those protected (anti-HBs titer > = 10 mlU/ml) rose from 42.8% after primary immunization to 82% after the booster. The mean anti-HBs titer, which remained low in the overall group, was significantly lower in the subjects who resumed drinking during the follow-up period than in those who did not. This suggests a direct influence of alcohol itself on the response, because none of our patients had cirrhosis and none were clearly malnourished. Among the 17 patients for whom the 2-year post-booster anti-HBs titer could be determined, all those with a 1 month postbooster titer above 1000 mlU/ml still had a high anti-HBs level (> 100), whereas 80% of those with a 1-month postbooster titer < 1000 had 2 years later only a low (< 100) or even an unprotective anti-HBs level; this means that only the latter should be considered for a new booster injection. Our data indicate that protection against hepatitis B virus can be achieved in a good proportion of alcoholics with a full vaccination protocol. We suggest that efficacy should be evaluated 1 month after the booster, and that patients with low postbooster anti-HBs titers should be tested at regular intervals, because they can also be protected provided an adapted schedule of further injections is conducted. PMID- 8488972 TI - Similar effects of ethanol and tert-butanol on amino acid concentrations in rat serum and liver. AB - Both metabolic and nonmetabolic mechanisms have been proposed to the plasma amino acid decreasing effect of an acute ethanol load. We used tert-butanol, an alcohol that is only minimally metabolized, as a tool to explain the mechanism behind the amino acid decreasing effect of ethanol. Acute administration of tert-butanol was found to exert a decreasing effect on rat serum amino acid concentrations similar to that of ethanol, indicating that the mechanism of the amino acid decreasing effect of ethanol is primarily due to ethanol itself and not to its oxidation. Ethanol and tert-butanol also had similar effects on liver amino acid concentrations, including an increase in the glycine concentration and decrease in the concentrations of glutamate, alanine, leucine, and tyrosine. PMID- 8488973 TI - Migration of cortical neurons is altered by gestational exposure to ethanol. AB - Rats prenatally exposed to ethanol exhibit a variety of structural anomalies in the central nervous system. One of the key features of experimental fetal alcohol syndrome is microencephaly. Cerebral cortex is particularly susceptible to the effects of prenatal exposure to ethanol. Its total mass is reduced, it is thinner, and it contains fewer neurons and glia. Various studies in rats and humans suggest that chronic early exposure to ethanol leads to a massive reorganization of cortex characterized by heterotopic clusters of neurons. A pulse and chase study with [3H]thymidine autoradiography was used to determine if gestational exposure to ethanol leads to defects in neuronal migration. Rats were fed an ethanol-containing diet between gestational day (G) 6 and G21, pair-fed a liquid control diet, or fed chow. Ethanol delayed the migration of early generated neurons (those born on G13) to deep cortex by 2 days. Moreover, the migration of late-generated neurons (those born on G21) was delayed 4 to 6 days by ethanol, and often these neurons terminated their migration in ectopic locations. Ethanol significantly decreased the rate of migration and the time postmitotic cells remained in the proliferative zones. On the other hand, ethanol did not have a significant effect on the rate of cortical expansion and the fraction of cells that left the proliferating population in order to migrate to cortex. Thus, the migration of young neurons was profoundly altered by prenatal exposure to ethanol. Such delays may lead to a desynchronization of cortical development that makes it impossible for cortical neurons to establish a normal circuitry. PMID- 8488974 TI - Enhanced expression of the inhibitory protein Gi2 alpha and decreased activity of adenylyl cyclase in lymphocytes of abstinent alcoholics. AB - Ethanol exposure alters signal transduction through the adenylyl cyclase (AC) system. To elucidate the basis for this effect, we investigated the AC system in peripheral lymphocytes from abstinent alcoholic men (n = 22), actively drinking alcoholic men (n = 41), and nonalcoholic control men (n = 16). Immunoblot analysis of lymphocyte membranes from abstinent alcoholics demonstrated a 3.0 fold increase in the level of Gi2 alpha protein (p < 0.05) compared with controls. However, levels of Gs alpha protein were similar in both groups. Abstinent alcoholics had a 2.9-fold increase in Gi2 alpha mRNA (p < 0.001) and a 2.7-fold increase in Gs alpha mRNA (p < 0.03) compared with lymphocytes from control subjects. Actively drinking alcoholics, in contrast, had unaltered Gs alpha protein, Gi2 alpha protein, and Gi2 alpha mRNA levels compared with control subjects, but did have a 1.8-fold increase (p < 0.01) in Gs alpha mRNA. Consistent with enhanced Gi2 alpha expression, lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E1-, guanosine 5'-0-(3 thiotriphosphate)-gamma S-, and forskolin-stimulated AC activity compared with both controls and actively drinking alcoholics (p < 0.05). We conclude that lymphocyte AC is reduced during abstinence from alcohol and enhanced expression of the inhibitory G-protein, Gi2 alpha, may account for this change. PMID- 8488975 TI - Role of gangliosides in behavioral and biochemical actions of alcohol: cell membrane structure and function. AB - Alcohol exerts its pharmacological effects in adult brain by altering the physicochemical properties of cellular plasma membranes. Although alcohol does induce changes in membrane lipid composition, studies to relate these alterations to the development of behavioral tolerance to alcohol and the withdrawal effects have been unsuccessful. Actions of alcohol on developing brain are even more complex. Some of the reported effects include inhibition of embryogenesis, cell migration, and differentiation, including synaptogenesis. Gangliosides have neuroprotective action against a variety of neural insults (e.g., mechanical injury, drug toxicity, or hypoxic insult). This review addresses the role and significance of gangliosides in the CNS pathophysiology of alcohol exposure, as well as the effect of changes in endogenous gangliosides on membrane structure and function. We also describe the role of exogenous gangliosides in prevention of alcohol (acute and/or chronic)-induced CNS (prenatal and postnatal) neurotoxicity through their action on cellular plasma membranes. We propose that ganglioside's neuroprotective effects against alcohol neurotoxicity involve protection and restoration of plasma membrane structure (proteins and lipids) and thereby its function (ionic homeostasis, neurotransmitter receptor-mediated signal transduction). Thus gangliosides may have potential therapeutic use in treatment of alcohol-related problems. PMID- 8488976 TI - Selective inhibition of luteinizing hormone action by ethanol in cultured human granulosa cells. AB - To extend further our previous observations on the inhibition of luteinizing hormone (LH)-induced increases in steroid secretion by ethanol (EtOH) (Alcohol. Clin. Exp. Res. 14:522-527, 1990), cultured human granulosa cells were pretreated with several EtOH concentrations (0-100 mM), and cells were stimulated with human LH (25 ng/ml) or human follicle stimulating hormone (FSH) (100 ng/ml) and the secretion of 17-beta-estradiol (E2) and progesterone (P) was measured. EtOH significantly increased basal E2 secretion in a dose-related manner (0-20 mM); however, in the same concentration range EtOH did not produce consistent changes in FSH-stimulated E2 secretion. In contrast, EtOH decreased LH-stimulated E2 secretion between 0-20 mM such that at 20 mM EtOH, the positive effect of LH was abolished. EtOH increased P secretion by 40% at 20 mM and at 100 mM, there was a 100% increase. The FSH-stimulated P secretion was not consistently changed by EtOH, whereas LH-stimulated P secretion was decreased in a dose-dependent manner. LH/human chorionic gonadotropin (hCG) receptors in cells exposed to EtOH showed a 15% (p < 0.01) and a 47% decrease at 20 mM and 50 mM EtOH, respectively. At 50 mM EtOH, there was a decrease in LH/hCG receptor number from 2900/cell to 1670/cell, without a change in receptor affinity for hCG and 50 mM EtOH decreased LH/hCG receptors in intact granulosa cells in a time-dependent manner. These results indicate that the selective effects of EtOH on LH action in human granulosa cells may be mediated in part by an action on LH/hCG receptors. PMID- 8488977 TI - Cholesterol exchange and lateral cholesterol pools in synaptosomal membranes of pair-fed control and chronic ethanol-treated mice. AB - Most studies on effects of ethanol on membrane cholesterol have reported on changes in the total or bulk amount of cholesterol. Membrane cholesterol, however, can be described in terms of its kinetics and domains. The kinetics and size of lateral cholesterol exchangeable and nonexchangeable pools were examined in synaptosomes of pair-fed controls and chronic ethanol-treated mice. Effects of sphingomyelin, an exofacial leaflet phospholipid, that has been shown to affect cholesterol pools, were also examined. Radiolabeled small unilamellar vesicles were used to exchange cholesterol with synaptosomes. The total amounts of membrane cholesterol, phospholipid phosphorus, and the ratio of cholesterol to phospholipid did not differ between the pair-fed control and ethanol groups. In control mice, the rate constant (hr-1) and the t1/2 (hr) of cholesterol exchange were 0.065 +/- 0.001 and 10.7 +/- 0.25 (hr), respectively. The rate constant was significantly slower (0.053 +/- 0.001, p < 0.05) and the t1/2 significantly longer (13.33 +/- 0.58, p < 0.05) in synaptosomes of the ethanol group compared with the control group. The size of the exchangeable pool of cholesterol did not differ significantly between the two groups. Sphingomyelinase-induced hydrolysis of sphingomyelin significantly slowed cholesterol exchange with the largest effect in synaptosomes of the control group as compared with the ethanol group (p < 0.05). Hydrolysis of sphingomyelin had significantly (p < 0.05) less of an effect on cholesterol exchange in synaptosomes of the ethanol group. Membrane cholesterol can be described in terms of total content, transbilayer distribution, kinetics, and size of lateral pools.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488978 TI - Ethanol exposure increases total protein kinase C activity in human lymphocytes. AB - Human circulating lymphocytes were isolated and incubated with ethanol. Cytosolic, membrane-bound and total detergent extractable protein kinase C (PKC) activities were measured. Exposure to ethanol (100 mm) resulted in an increase in PKC activity, with membrane-associated PKC activity increasing with respect to cytosolic activity at 5 min of exposure. Higher concentrations of ethanol up to 200 mm were associated with increases in total detergent extractable PKC activity. Ethanol was the most potent of a series of straight chain alcohols studied for their effects on detergent-extractable PKC activity. PMID- 8488979 TI - "Binge" versus steady drinking: effects on the liver in the ovariectomized rat. AB - Substantial interest exists as to whether or not differential effects in liver injury based on the pattern of alcohol intake exist; and further, if they do, are they simply a function of the total dose over time. A rat model in which ethanol (ETOH) at doses of 12%, 24%, or 36% of total calories was isocalorically administered for 4 months either daily or intermittently (4 days of ETOH, 3 days of control diet, repeatedly) was used to assess this question. There were significant differences in the two feeding pattern groups between 36% ETOH rats for the liver weight corrected for body weight, the fat infiltration score, the total amount of ETOH consumed/mg body weight, the proportion of animals with a fat infiltration score > 2, and albumin levels. There was a significant difference between 12% ETOH rats for the liver weight corrected for body weight. Of particular relevance is the comparison to be made between Daily 12% ETOH and Binge 24% ETOH animals, because these two groups consumed an identical total amount of ETOH/mg body weight (Daily: 445 +/- 5 vs. Binge: 468 +/- 15) and thus these animals are comparable in terms of ETOH dose over time but different in terms of the pattern of ETOH exposure. There were no differences in the liver/body ratio (Daily: 235 +/- 6 vs. Binge: 232 +/- 4), fat infiltration score (Daily: 2.5 +/- 4 vs. Binge: 2.4 +/- 0.3), the proportion of animals with a fat infiltration score > 2 (Daily: 5/10 vs. Binge: 4/8), or albumin levels (Daily: 3.0 +/- 0.1 vs. Binge: 3.1 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488980 TI - Ethanol increases apoptotic cell death of thymocytes in vitro. AB - Exposure of animals to ethanol causes thymic atrophy in adults and fetuses. Whether direct effects of ethanol contribute to thymic atrophy or whether indirect effects are entirely responsible is at present unknown. In the normal animal, large numbers of thymocytes undergo a physiological form of cell death referred to as "apoptosis." To determine if ethanol affects the process of apoptosis, studies were undertaken in which mouse thymocytes were cultured overnight in the presence or absence of ethanol. Apoptotic cell death was analyzed by flow cytometric quantitation of apoptotic nuclei, by fluorometric measurement of DNA fragments, and by gel electrophoretic analysis of DNA fragments. Ethanol in concentrations of 0.2% to 0.8% produced significantly higher levels of apoptosis than were seen in control cultures. The DNA fragmentation was characterized as apoptotic on the basis of inhibition by aurintricarboxylic acid (an inhibitor of nucleases) and by the presence of characteristic oligonucleosomal-sized fragments of DNA. The effect of ethanol on apoptosis was additive to that induced by immobilized anti-CD3 monoclonal antibody. CD4+CD8+ cells underwent apoptosis as indicated by reduction in CD4 and CD8 surface antigen expression. An inhibitor of protein kinases (H-7) reduced the DNA degradation induced by ethanol and by anti-CD3. These results suggest that direct effects of ethanol contribute to thymic atrophy in alcohol-consuming animals. PMID- 8488981 TI - Saccharin intake predicts ethanol intake in genetically heterogeneous rats as well as different rat strains. AB - Saccharin and ethanol intakes were measured in seven strains of rats known to differ in their preferences for ethanol: The Fawn-Hooded (FH), alcohol-preferring (P) and Maudsley Reactive rats have been reported to drink ethanol voluntarily, whereas the alcohol-nonpreferring, Maudsley Nonreactive and Flinders Line (FSL and FRL) rats do not. Saccharin and ethanol intakes were highly correlated (r = +0.61) over all strains, with the FH rats drinking the most of both solutions. Correlation coefficients between pairs of drinking versus nondrinking rat strains were even higher. In a second experiment, genetically heterogeneous F2 progeny from cross-breeding the ethanol-preferring FH rats with the ethanol-nonpreferring Flinders Resistant Line (FRL) rats were studied. The results indicated a high positive correlation between saccharin and ethanol intakes (+0.65). These findings suggest that the association between saccharin and ethanol intakes previously reported in rat strains with different preferences for ethanol may have a similar genetic basis. PMID- 8488982 TI - Alcohol and aldehyde dehydrogenases in human esophagus: comparison with the stomach enzyme activities. AB - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes from surgical esophageal and gastric mucosa were compared by agarose isoelectric focusing. Two prominent ADH forms, designated mu 1 (equivalent to the recently reported mu-form) and mu 2, were expressed in all the 15 esophagus specimens studied, whereas only four of seven examined gastric specimens exhibited a weak to moderately strong mu 1-ADH activity band on the isoelectric focusing gels. pI values of the esophageal mu 1-ADH and mu 2-ADH, and the liver pi-ADH were determined to be 8.61, 8.13, and 8.90, respectively. mu-ADHs exhibited high Km for ethanol (12 mM) and low sensitivity to 4-methylpyrazole inhibition. ALDH3 (BB form) and ALDH1 were the major high- and low-Km aldehyde dehydrogenase in the esophagus, respectively. The ADH and ALDH activities were determined at pH 7.5 to be 751 +/- 78 and 29.9 +/- 3.0 nmol/min/g tissue, respectively (measured at 500 mM ethanol or at 200 microM acetaldehyde; mean +/- SEM; N = 15). The esophageal ADH activity was approximately 4-fold and the ALDH activity 20% that of the stomach enzyme. Because the presence of high activity and high Km mu-ADHs as well as low-activity ALDH1 were found in human esophageal mucosa, it is suggested that there may exist an accumulation of intracellular acetaldehyde during alcohol ingestion. This reactive and toxic metabolite may be involved in the pathogenesis of alcohol-induced esophageal disorders. PMID- 8488983 TI - The influence of age on blood alcohol levels and ethanol-associated immunosuppression in a murine model of ethanol consumption. AB - Several study findings indicate that with ethanol ingestion a number of changes occur in the immune system. We studied the effects of ethanol consumption on mice at various ages. We used a murine model in which young (age 6-8 weeks), middle aged (age 12 months), and old (age 24 months) male C57Bl/6 mice were pair-fed either a Leiber-DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet. Consumption of ethanol diet for 8 days resulted in high blood alcohol levels in young and old mice; low levels were observed in middle-aged mice. Middle-aged mice consumed more ethanol than did either young or old mice and had the lowest percent body weight loss of all three age groups. Proliferation of spleen lymphocytes to T-cell stimuli (concanavalin A and alloantigens) in both young and old mice fed ethanol was diminished. T-cell function was unchanged in middle-aged mice consuming an ethanol diet when compared with that observed in age-matched mice pair-fed control diet. No effect of ethanol on proliferation to lipopolysaccharide was noted in any group. Proliferative response of T cells to soluble anti-CD3 monoclonal antibody was also decreased in middle-aged and old pair-fed control mice when compared with young control mice. The proliferative response to soluble anti-CD3 in all three age groups of mice fed ethanol, however, was not significantly affected by ethanol consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488984 TI - Effect of chronic alcohol feeding on hepatic iron status and ferritin uptake by rat hepatocytes. AB - Alcohol abuse is known to cause disturbances to iron homeostasis in man and is associated with elevated serum ferritin levels. We have previously shown that ethanol metabolism in the rat hepatocyte is associated with an immediate reduction in ferritin uptake by this cell. In this study we have examined the effect of pair-feeding the Lieber-DeCarli liquid alcohol diet on ferritin uptake by rat hepatocytes. Rat liver ferritin was radiolabeled with 59Fe in vivo and isolated by conventional techniques. Rats were pair-fed the Lieber-DeCarli liquid alcoholic diet for 4-6 weeks. Hepatocytes, isolated from their livers by collagenase perfusion, were incubated with [59Fe]ferritin in L-15 medium at 37 degrees C and 4 degrees to measure ferritin uptake and binding. The in vitro effect of ethanol on these hepatocytes was also studied. Ferritin and iron parameters were measured in the sera and hepatocytes of these animals and a comparable group of normal chow-fed rats. The rate of ferritin uptake by hepatocytes from alcohol-fed rats was significantly faster than that of their pair-fed controls (0.743 +/- 0.061 vs. 0.540 +/- 0.042 ng/min/10(6) cells, p < 0.05). However, the rats on Lieber-DeCarli control diet exhibited a lower hepatocyte ferritin uptake rate than chow-fed animals (79.3 +/- 8.1% of the control values, p < 0.01). In vitro incubation of cells in 100 mM ethanol resulted in less inhibition of ferritin uptake by hepatocytes from alcoholic rats than from their pair-fed controls (11 +/- 7.1% inhibition vs. 43.6 +/- 10.7% for controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488985 TI - Decreased synapse-to-neuron ratio in rat locus ceruleus following chronic ethanol feeding. AB - Effects of chronic ethanol exposure on the synapse-to-neuron ratio of rat locus ceruleus were investigated. Male Sprague-Dawley rats were given an ethanol containing liquid diet for 4 months starting at an age of 5 weeks. Littermates, given isocaloric amounts of an ethanol-free diet, served as control. The animals were perfusion fixed using a mixture of glutaraldehyde and paraformaldehyde. Synapse-to-neuron ratio was estimated by the double disector method and calculated from (Ns/A) x (Nsec -1) / (Nn/A) where Ns/A is the number of synapses per unit area estimated in a disector with a height of on section and Nsec -1 is height of the disector, i.e., the number of sections, used for estimating the number of neurons per area (Nn/A). The mean estimated synapse-to-neuron ratio was 2046 +/- 544 (SD) in ethanol-fed rats and 4291 +/- 1171 (SD) in control rats. The difference is statistically significant (p < 0.05). The finding may be of relevance for understanding the development of abuse, tolerance, drug dependence, and abstinence reactions. PMID- 8488986 TI - Potential role of 5HT1C and/or 5HT2 receptors in the mianserin-induced prevention of anxiogenic behaviors occurring during ethanol withdrawal. AB - A single dose of mianserin (a 5HT1C/5HT2 antagonist), administered 1 hr, 48 hr, or 7 days before testing, was evaluated for its efficacy in alleviating or preventing the occurrence of anxiogenic behaviors observed during ethanol withdrawal. Other behavioral experiments using selected drug interactions were conducted to examine whether the effect of mianserin was related to a long-term modification of 5-hydroxy-tryptamine (5HT) receptor function. Rats were fed a liquid diet containing 4.5% ethanol for 4 days. They were tested on the elevated plus-maze (EPM) 12 hr (acute withdrawal) and 5 days (protracted withdrawal) after the last ethanol dose. Ethanol withdrawal induced a pattern of "anxiogenic" behavior that consisted of reduced activity (total entries) and a reduced proportion of open arm activity. Mianserin, injected as a single dose given either 1 hr (0.16-5 mg/kg, ip) before testing or given (20 mg/kg, ip) on the morning of the 3rd day of ethanol administration, i.e., 48 hr and 7 days before testing, dose-dependently prevented or reversed the ethanol withdrawal induced reduction in open-arm activity. In contrast, the 5HT1C/5HT2 receptor agonist (+/- )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOl) did not affect behaviors in the EPM in ethanol-naive rats, nor in those undergoing ethanol withdrawal. However, although there was a marked tolerance to DOl-induced body shakes (a measure of 5HT2 function) during withdrawal, DOl reversed the action of mianserin in the EPM. The 5HT1 receptor agonist, 5HT2 receptor antagonist 1 naphthyl-piperazine (1-NP) reduced open-arm activity in ethanol-naive rats and this action was enhanced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488987 TI - Chronic cadmium exposure attenuates ethanol-induced hypoalgesia in the adult rat. AB - Adult male rats were exposed to a diet containing either 100 ppm added cadmium (Cadmium-Diet), or a control diet containing no added chemicals (Control-Diet) for 67 days prior to pain reactivity testing using a tail-flick procedure. Rats were placed in restraining tubes for a 20-min acclimation period, then baseline tail-flick latencies in response to a radiant heat source were measured. Subsequently, half the animals from each group were serially injected intraperitoneally with either 0.5, 1.0, 1.5, or 2.0 g/kg body weight of a 20% v/v ethanol solution, and the other half of the animals were injected with an equivalent volume of saline. Tail-flick latencies were reassessed at 20-min intervals over the next 2 hr. Results indicated dose-dependent ethanol-induced hypoalgesia in the Control-Diet animals for the two highest doses, but ethanol induced hypoalgesia was evident only at the highest dose for the Cadmium-Diet animals. Further, the magnitude of this hypoalgesic effect was significantly lower for the Cadmium-Diet animals than the Control-Diet animals at the 2.0 g/kg dose. Results are discussed in terms of an attenuation of the pharmacological properties of ethanol by cadmium. PMID- 8488988 TI - The alcohol beverage warning label: when did knowledge increase? AB - This article presents data on the awareness of the alcohol beverage warning label among a sample of 5,169 inner city African-American gravidas seeking prenatal care. While the label law was implemented in November 1989, a significant increase in knowledge of the label did not occur until March 1990. Women who predominantly consumed wine coolers and beer, and those under age 30 were more likely to know about the label than their counterparts. PMID- 8488989 TI - Dietary carbohydrate accelerates ethanol elimination, but does not alter hepatic alcohol dehydrogenase. AB - In naive animals the rate of ethanol elimination is dependent on the hepatic alcohol dehydrogenase activity. Carbohydrates have been shown to modify ethanol metabolism by a mechanism that has not been determined. In this study, adult female rats, fed chow diets supplemented with fructose or glucose in their drinking water for 10 days demonstrated significantly greater ethanol elimination rates (4.85 +/- 0.28 and 4.92 +/- 1.56 microM ethanol/min/g liver, respectively) than rats receiving water (3.65 +/- 0.29). The hepatic alcohol dehydrogenase activity of the fructose (1687 +/- 101 nM ethanol/min/g liver) and the glucose (1832 +/- 15)-supplemented rats were not significantly different from that of control rats (1845 +/- 160). Dietary carbohydrate supplementation, therefore, enhanced ethanol elimination, but did not alter the activity of alcohol dehydrogenase. Thus the changes in the ethanol elimination rate following carbohydrate loading were not the consequence of an alteration in hepatic alcohol dehydrogenase. PMID- 8488990 TI - Bestatin, an aminopeptidase B inhibitor, selectively reduces alcohol intake in rats. AB - Extensive research has shown that manipulations that augment activity in the renin-angiotensin system can reduce alcohol intake. Inhibition of aminopeptidase B and M can prolong the action of angiotensin (ANG) II and ANG III by preventing their degradation. This study assessed the ability of bestatin, an aminopeptidase B and M inhibitor, to decrease alcohol intake. Bestatin produced a dose-dependent reduction in alcohol intake without altering water intake. The angiotensin antagonist Sar1Thr3-ANG II, however, did not attenuate the effect of bestatin, suggesting that the reduction in alcohol intake was mediated by a system other than the renin-angiotensin system. Bestatin (Ubenimex) is used extensively in Japan as an anticancer agent. It has a low toxicity and is readily absorbed after oral administration. Although further research is needed to uncover the mechanism of its effect, the potential of this drug as an adjunct for the treatment of alcohol abuse should be evaluated. PMID- 8488991 TI - [Anesthesia induction using etomidate in a lipid emulsion]. AB - The use of etomidate as an anaesthetic induction agent has been hampered significantly by unwanted side effects such as pain on injection and thrombophlebitis. Investigations by Doenicke et al. have shown that the solubilizer propylene glycol is responsible for these side effects and that they can be avoided by the use of a lipid emulsion formulation. It was the goal of the present study to quantitate the reduction of thrombophlebitis and pain on injection following both formulations under double-blind study conditions. METHODS. In 100 patients anaesthesia was induced either with a new galenic formulation of etomidate--etomidate in lipid emulsion formulation (Lipofundin MCT 20%; eto-lip)--or with etomidate in propylene glycol 35% (eto-pg). Both groups received 0.3 mg kg-1 etomidate in double-blind randomized fashion. After the injection of etomidate the venous cannula was removed. The observing anaesthetist was unaware of the study drug used, to guarantee blinded investigation conditions. Discomfort and pain during and following injection were recorded, as was local skin irritation. Venous sequelae were assessed for 7 days following injection to register the occurrence of thrombophlebitis. RESULTS. Demographic data were not different between the two groups. For induction of anaesthesia the same dose of both preparations was necessary, and no difference in heart rate and blood pressure before, during or after anaesthesia induction was observed. Pain on injection (78% vs 14%), myoclonus (24% vs 8%) and local skin reaction (50% vs 6%) were present significantly more often in the eto-pg group (P < 0.01; P < 0.05 respectively, chi-square test) than in the eto-lip group. On the 1st and 2nd postoperative days, examination of the injected vein revealed a significantly higher incidence of symptoms of thrombophlebitis in the group treated with eto-pg (25% vs 3%). CONCLUSION. From these results it is concluded that in terms of vein compatibility the new galenic formulation of etomidate with lipofundin MCT 20% is superior to the propylene glycol preparation while pharmacodynamic properties seem not to be affected. PMID- 8488992 TI - [Cardiopulmonary effects of CPPV (continuous positive pressure ventilation) and IRV (inverse ratio ventilation) in experimental myocardial ischemia]. AB - Continuous positive pressure ventilation (CPPV) is an established therapy for treatment of acute respiratory failure (ARF). However, cardiac performance may be severely disturbed due to elevated intrathoracic pressure, inducing a decrease in cardiac output (CO) and oxygen delivery (DO2). Alternatively, mechanical ventilation with prolonged inspiratory to expiratory duration ratio (inversed ratio ventilation IRV) has been successfully used in ARF. No data are available about IRV in acute haemodynamic oedema. Thus, the cardiopulmonary effects of CPPV (positive end-expiratory pressure [PEEP] = 10 cm H2O) and IRV (inspiration to expiration duration ratio [I:E] = 3.0) were studied in nine dogs (body weight 29.9 +/- 4.3 kg) before and after induction of myocardial ischaemia. METHODS. Continuous intravenous anaesthesia and muscle paralysis were provided by 1.2 mg.kg-1 x h-1 piritramide and 0.08 mg.kg-1 x h-1 pancuronium, and the animals were ventilated with intermittent positive pressure ventilation (IPPV) as reference method. Cardiocirculatory performance was determined by means of heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP) and left ventricular end-diastolic pressure (LVEDP). Cardiac output (CO) was determined by thermodilution method. Systemic vascular resistance (SVR) was calculated. Pulmonary function was assessed by arterial and mixed venous blood gas tension for oxygen (PaO2, PvO2) and carbon dioxide (PaCO2). Functional residual lung capacity (FRC) was measured by means of the foreign gas wash-in method using helium as inert gas, and determination of extravascular lung water (EVLW) using the thermal-dye indicator technique. CPPV and IRV were studied in random sequence in the control phase and 60 min after induction of acute left ventricular ischaemia, which was achieved by occlusion of the ramus interventricularis anterior. RESULTS. During the control phase CPPV induced an increase in MPAP (P < 0.05), CVP (P < 0.05) and PAOP (P < 0.05). HR and MAP remained unchanged, whereas CO decreased by 16% (P < 0.05). FRC was elevated by 25 ml.kg-1 (P < 0.01), but not EVLW (9.1 +/- 3.5 ml.kg-1). There was no improvement in oxygenation; instead, oxygen delivery (DO2) decreased (P < 0.05). During inversed ratio ventilation MPAP, CVP, PAOP increased, but less than during CPPV. FRC was elevated mu 7.0 ml.kg-1 (P < 0.05), which was significantly less than during CPPV (P < 0.05). EVLW revealed no differences. During IPPV in the ischaemia phase cardiopulmonary performance deteriorated significantly. CO decreased by 19% (P < 0.05), whereas HR, MPAP, CVP and PAOP increased (P < 0.05). PaO2 was lower (P < 0.05) and alveolo-arterial PO2 gradient (PAaO2) increased (P < 0.05). All animals revealed moderate pulmonary oedema (EVLW = 15.1 +/- 8.4 ml.kg-1) (P < 0.01) and a lower FRC. Mechanical ventilation with PEEP significantly improved oxygenation and FRC; however, DO2 was slightly lower than during IPPV (not significant). IRV elevated PaO2, FRC and DO2, since CO was not depressed when compared with IPPV. CONCLUSIONS. CPPV and IRV may induce a recruitment of collapsed or hypoventilated lung areas, which is more pronounced during CPPV. During both modes of ventilation, oxygenation was improved without apparent changes in EVLW. Haemodynamic performance was more impaired during CPPV, and no improvement of left ventricular function secondary to an elevated intrathoracic pressure was observed. Occlusion of the RIVA coronary artery typically induces an infarction of 35% of left ventricular muscle mass; however, non-ischaemic myocardium reveals an unchanged or increased contractility. Thus, a reduction of left ventricular preload secondary to CPPV mainly contributes to haemodynamic depression, which is less pronounced during IRV due to a lower peak inspiratory airway pressure and mean airway pressure. IRV may be useful for mechanical ventCntCo PMID- 8488993 TI - [Acupressure in the prevention of postoperative nausea and vomiting]. AB - Despite modern anaesthetic procedures, postoperative nausea and vomiting are still the side-effects most often mentioned: acupressure is reported to be an additional method of preventing these effects in minor gynaecological surgery. We investigated the effectiveness of acupressure in patients undergoing gynaecological operations of longer duration (6-8 h) in a verum acupressure group compared to a placebo group. Before beginning the study we investigated a control group to find out the frequency of emesis. In the worst case of nausea that we encountered, 80% in the 0-6 h postoperative period, the number of random samples for the acupressure and placebo groups was calculated (30 patients in each group). The error for alpha was established at 5% and the reduction of nausea was 50%. METHODS. The female patients were 18 to 65 years old (ASA group I and II). Acupressure was carried out by fastening small metal bullets at the point P 6 to each forearm by means of an elastic bandage. The bullets were left there for 24 h. The premedication anaesthesia, postoperative analgesia, and antiemetic treatment were standardized. During a 24-h period we investigated the incidence of nausea and vomiting. RESULTS. The anthropometric data, the duration of surgery and the amount of postoperative analgesia were comparable between the three groups. Verum acupressure obtained a statistically significant and relevant reduction in nausea up to the 6th postoperative hour in comparison with the placebo group (P = 0.03). Nausea was reduced from 53% in the placebo group to 23% in the acupressure group. CONCLUSION. As demonstrated in this group of longer gynaecological surgery patients as well as in chemotherapy-induced nausea and vomiting, we were able to demonstrate that acupressure is an effective method of preventing nausea and vomiting without any side-effects. It is a valuable addition to the prevention of postoperative nausea and vomiting. Further studies should be conducted to investigate this possibility further. PMID- 8488994 TI - [Continuous monitoring of spontaneous postoperative respiration. 3. The effect of amiphenazole on cutaneous oxygen and carbon dioxide partial pressure following gynecologic surgery under halothane anesthesia]. AB - METHODS: In an attempt to verify non-invasive respiratory monitoring for patients in the early postoperative period, cutaneous O2 and CO2 pressures were monitored in 30 female patients recovering from major gynaecologic surgery under halothane anaesthesia. In a double-blind and randomized fashion, in the recovery room the patients received a single intravenous bolus injection of placebo or 150 mg amiphenazole, a respiratory stimulant. The data were collected and stored in a personal computer, using the TCM3 system with a combination electrode for simultaneous measuring of cutaneous oxygen and carbon dioxide partial pressures (TINA, Radiometer) at 30-s intervals. The overall observation period was 240 min. Means and standard deviations were calculated for individual data and for data pooled at 15- or 60-min intervals. Groups were compared by means of the chi 2 test, Student's t-test, Wilcoxon rank sum test or analysis of variance (level of significance P < or = 0.05). RESULTS: The study groups were comparable with respect to demographic and anaesthesiological data. The partial pressures for both O2 and CO2 were not statistically significant between groups. Electrode heating was slightly higher with amiphenazole (n.s.), indicating a trend for peripheral vasodilation without a true improvement of spontaneous ventilation. pctO2 and pctCO2 levels were decreased or elevated, respectively, in the first observation hours and slowly returned to normal within the 240-min observation period. Episodes of hypercapnia (pct-CO2 > 50 or > 55 mm Hg) were frequent in the first 2 h (10-30% of individual data for pctCO2 > 50, 2-7% for pctCO2 > 55, respectively), indicating the need for close monitoring of spontaneous respiration after general anaesthesia with halothane. DISCUSSION AND CONCLUSION: The present study confirmed that spontaneous respiration in the early postoperative period can be monitored non-invasively by measuring transcutaneous partial pressures of carbon dioxide and, less precisely due to large individual variations, oxygen. It showed that spontaneous respiration deteriorates after gynaecological surgery under halothane anaesthesia and recovers slowly during the next 4 h. The respiratory stimulant amiphenazole (150 mg i.v.) was of no significant value with respect to the improvement of ventilation. PMID- 8488995 TI - [A comparison of different endotracheal tubes. Tracheal cuff seal, peak centering and the incidence of postoperative sore throat]. AB - The study objective was to evaluate cuff seal, tube tip position and incidence of postoperative sore throat in three different endotracheal tubes: the reusable Rusch "red rubber" tube (low-volume, high-pressure cuff) and the disposable Rusch "Super Safety Clear" and Mallinckrodt "lo-pro" tubes (both high-volume, low pressure cuffs). METHODS: In a prospective randomized trial, 150 consecutive patients scheduled for minor orthopaedic surgery under standardized general anaesthesia, including standardized cuff pressure control, were allocated to one of the three types of endotracheal tube. Leakage and intratracheal tube tip position were investigated by means of fiberoptic tracheoscopy via the endotracheal tube, preceded by pharyngeal instillation of indigocarmine. The semi standardized interviews for the recording of postoperative sore throat were performed once a day under double-blind conditions from the day of operation to postoperative day 3. Statistical independence testing was based on the chi 2 test, significance was assumed at P < 0.05. MAIN RESULTS: A past-cuff leakage of the pharyngeally instilled dye was found in three patients with "red rubber" tubes. In all of these cases the tracheal cross section deviated markedly from circular. The tips of the "Super Safety Clear" tubes tended to be better centred (P = 0.099). Bad tip position, however, had little influence on postoperative throat complaints (P = 0.394). The differences in incidence of postoperative throat complaints between the "red rubber" (48.9%), "Super Safety Clear" (35.6%) and "lo-pro" tubes (34.1%) did not reach the 5% level (P = 0.288). Such complaints, however, were significantly more frequent in females and in obese patients who exceeded their Broca weights by more than 25%. By contrast, postoperative throat complaints did not vary statistically significantly by age group, tracheal cross-sectional shape, use of atropine or duration of intubation. CONCLUSION: Despite the economic (usable up to 100 times) and ecological (less PVC waste) advantages of the rubber tube, the disposable tubes with high-volume, low-pressure cuffs tended to be superior regarding cuff seal, tube tip position and incidence of postoperative throat complaints. Nevertheless, the continued use of "red rubber" type reusable tubes may be justified in cases where the tube has to stay in place for only a short time. PMID- 8488996 TI - [Ethics and research in emergency medicine]. PMID- 8488997 TI - [Research in emergency medicine. Ethical requirements]. AB - Having pointed out some curriculum goals in medical ethics, a plea is made for extensive animal experimentation, especially in emergency medicine in order to minimize necessary investigations in human beings. Although certain groups of patients (persons in custody, minors) are protected nowadays against unjustified research activities by legal restraints, well-designed therapeutic (even nontherapeutic) investigative projects can be facilitated under certain conditions. The same attitude might be adopted for "special" populations (e.g., HIV patients), which are very often excluded for various reasons. Research protocols and statistical evaluation should not be permitted to differ in these groups in comparison to "normal" patients. The issue of "informed consent" in emergency research with the main emphasis on resuscitation cannot be considered as resolved since many patients are unconscious or at least incompetent. Irrespective of the number of legislative constructions proposed mainly in the USA ("proxy consent", "substitute decision making," "deferred consent"--the latter being already declared a misnomer by its "inventor", ethical standards might better be adapted to the respective situations guided by competent ethical committees. As for the particulars of research protocols, randomization combined with a blind or double-blind study design is now considered to be ethically desirable by a majority of authors, the same holding true for risk stratification and sequential test procedures in order to reduce the number of patients required. The "theory of intuitive thinking" is briefly touched upon as a futuristic investigative method and/or decision strategy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8488998 TI - [The anterior sonographic-guided celiac plexus blockade. Review and personal observations]. AB - The coeliac plexus block is an approved method for the relief of upper abdominal pain due to cancer of the upper intra-abdominal viscera or to chronic pancreatitis. While there are many reports concerning the posterior approach to the coeliac plexus block, little attention has been given the anterior approach. There are two ways of implementing the anterior approach to the coeliac plexus: CT-guided and the ultrasound guided approach. METHODS. The ultrasonic-guided anterior approach to the coeliac plexus block is used with the patient in the supine position. The aorta and discharge of the truncus coeliacus or the a. lienalis respectively, are ultrasonographically presented at two levels. After setting local cutaneous and subcutaneous anaesthesia, a 15-cm-long 25 G-needle is introduced into the epigastrium. The point of the needle is--ultrasonographically guided--inserted into the pre-aortic area near the discharge of the truncus coeliacus. The position of the needle point is ultrasonographically controlled on two levels. For the enforcement of a diagnostic coeliac plexus block after careful aspiration on two levels, 10 ml of bupivacaine 0.5% is injected. The spread of the solution is evaluated by ultrasound. If the needle position is correct; a few minutes later the patient has a feeling of warmth in the upper abdominal region. For the enforcement of a neurolytic coeliac plexus block 10 ml ethanol 96% and 10 ml prilocaine 1% can be administered. The two solutions are applied as small volumes in permanent succession. Thus the burning pain, which is often observed after the injection of alcohol, is avoided. RESULTS. In the literature there are only a few reports, about the results and side-effects after use of the anterior approach in the coeliac plexus block. The results of these investigations and our own show total pain relief or at least good pain reduction by at best 85%. The reduction in pain achieved continues in as many as 60% of the treated patients. There is the possibility to stop or at least reduce the analgesic premedication. These results are comparable with those after using the posterior approach to the coeliac plexus block. When carrying out the anterior approach in the coeliac plexus block, most of the patients showed increased intestinal motility. Therefore, about 60% of all patients had transitory diarrhoea. In 12-25% of the patients orthostatic hypotension was observed. This side-effect is avoided by an appropriate infusion before enforcement of the block. In a frequency of 4-100% the occurrence of burning pain was reported during injection of the alcohol. No serious side-effects were observed. CONCLUSIONS. The results concerning total pain relief or at least pain reduction are comparable to the posterior approach for the block. Nevertheless, there are some advantages to the ultrasound-guided anterior approach. There is less risk using this technique. No methodological complications have been observed so far. There is no risk of neurological complications such as paraplegia. Because the patients remain in the supine position, the anterior approach to the coeliac plexus block is suitable for terminally ill patients, who are not able to tolerate the prone position and need careful supervision and good ventilation. Also, no contrast medium is necessary. Only a small volume of local anaesthetics or alcohol is required. We prefer the anterior approach of the coeliac plexus block as a fast, safe and cost-effective method, which should receive increasing attention during the next few years. PMID- 8488999 TI - [Laterosubmental tracheal intubation. An alternative method to nasal-oral intubation or tracheostomy in single-step treatment of panfacial multiple fractures or osteotomies]. AB - In single-step surgery of panfacial fractures or conversion osteotomies of the visceral cranium, nasal as well as oral intubation or tracheal intubation via tracheostomy is necessary. If complicated tracheostomy is not done, intraoperative nasal-oral repositioning of the tube is required. In order to avoid the risks of repositioning the endotracheal tube or tracheostomy, we suggest a new alternative method called laterosubmental tracheal intubation. After a laterosubmental fistula is created at the base of the mouth, directly behind the anterior mandibular dentition, the tube is guided through the oral floor, lateral to the muscles and the salivary duct, and fixed extraorally. The advantages of this method are: no more intraoperative repositioning of the endotracheal tube and no need for tracheostomy, thus eliminating the risks and side effects, as well as tracheal scarring, and free accessibility of the operative field. PMID- 8489000 TI - [The diagnosis of brain death. Guidelines in Germany, Austria and Switzerland]. AB - Today's modern medicine with its nearly limitless possibilities requires a well founded diagnosis of brain death. After this diagnosis continuation of intensive medical care becomes meaningless, or an essential precondition for organ donation is fulfilled. In view of the delicate problems involved, it is essential that brain death be diagnosed uniformly and in well-founded fashion. Responsible institutions in Germany, Austria and Switzerland have issued guidelines, criteria and aids to decision making that vary only insignificantly. PMID- 8489001 TI - [Comments on the work by W. Tolksdorf et al. The effects of carbon dioxide pneumoperitoneum in laparoscopic cholecystectomy on postoperative spontaneous respiration]. PMID- 8489002 TI - A study of sensitized lanthanide luminescence in an engineered calcium-binding protein. AB - In this study, the CD loop of the Ca(2+)-binding protein oncomodulin was replaced by a high-affinity, metal-binding sequence that was found to reverse the order of fill of the two sites in the protein. A cysteine was included at position 7 of this sequence, i.e., DKNADGCIEFEE. The cysteine allowed covalent attachment of chromophores to the loop that could subsequently be tested for their ability to sensitize the luminescence of Tb3+ or Eu3+ bound in the loop. 7-Diethylamino-3 ((4'-iodoacetylamino)phenyl)-4-methylcoumarin was the most efficient Eu3+ sensitizer studied, consistent with a mechanism of energy transfer that involves the triplet state of the donor. 4-Iodoacetamidosalicylic acid was the most efficient Tb3+ donor tested. Levels of lanthanide ion and labeled C3 as low as 5 x 10(-10) mol/liter could be detected. This protein chelator system has potential to be a useful, flexible complement to the organic chelators currently used in lanthanide-based, time-resolved luminescence immunoassays. PMID- 8489003 TI - Catabolism of deoxycytidine in human peripheral blood mononuclear cells and its interference with the determination of in situ thymidylate synthase activity. AB - Resting and stimulated human peripheral blood lymphocytes and monocyte-derived macrophages were incubated with tritiated deoxycytidine labeled at the 5 position. Release of tritiated water into the medium was thereupon detected utilizing its lack of binding to active charcoal, which is an established technique to measure in situ thymidylate synthase activity. It was found that tritiated dihydrouracil, a deoxycytidine catabolite, was formed during incubation with tritiated deoxycytidine. Like water, dihydrouracil does not bind to active charcoal, and its presence in the cell medium can result in an overestimation of the in situ thymidylate synthase activity. The catabolism of dCyd was highest in macrophages where 25% of the added dCyd (0.5 microM, 0.5 nmol/million cells) had been converted to dihydrouracil after 30 min, and 90% after 12 h. The in situ thymidylate synthase activity was found to be the highest in stimulated lymphocytes. If the interference of dihydrouracil had not been considered, the activity in macrophages would have been greatly overestimated and would have appeared to be higher than that of stimulated lymphocytes. PMID- 8489004 TI - Analysis of the neutral glycan fractions of glycosyl-phosphatidylinositols by thin-layer chromatography. AB - The radiolabeled neutral glycan fractions of both glycosyl-phosphatidylinositol (GPI) protein anchors and related glycolipids were analyzed by thin-layer chromatography on silica gel 60, using butanol:ethanol:water (4:3:3, v/v) or a combination of 1-propanol:acetone:water (9:6:5, v/v and 5:4:1, v/v) as solvents. Dextran acid hydrolysates were used as standards, and oligomers up to 11 glucose units could be resolved. A comparison of 18 GPI-glycan standards revealed that their migration was dependent mainly on the size of the oligosaccharide. Isomers were generally not resolved, with the exception of Man alpha 1-6Man alpha 1-4AHM and Man alpha 1-3Man alpha 1-4AHM. Structures containing galactofuranose or GalNAc were well resolved from structures containing only Galp and/or Manp. The utility of this method for the microsequencing of radiolabeled neutral glycans derived from two GPI glycolipids, using exoglycosidases and chemical treatments, is demonstrated. This method is a simple and useful complement to the existing chromatographic techniques. PMID- 8489005 TI - Determination of platinum in urine, ultrafiltrate, and whole plasma by isotope dilution gas chromatography-mass spectrometry compared to electrothermal atomic absorption spectrometry. AB - Isotope dilution gas chromatography-mass spectrometry (GC-MS) and electrothermal atomic absorption spectrometry (EAAS) are compared for platinum (Pt) determination in urine, plasma ultrafiltrate, and plasma samples from a patient undergoing cisplatin therapy. The isotope dilution GC-MS method is based on the use of lithium bis(trifluoroethyl)dithiocarbamate as a chelating agent and enriched 192Pt as an internal standard. Pt isotope ratios were measured using a Finnigan MAT 8230 organic mass spectrometer, and Pt concentrations were calculated from different sets of isotope ratios in the molecular ion of the Pt chelate. In the EAAS method, Pt concentrations were determined using three different approaches. These were: (i) calibration curve based on aqueous standards containing Pt in 10% HCl, (ii) standard addition, and (iii) matrix digestion followed by standard addition. Good agreement was obtained for Pt concentrations determined by GC-MS and EAAS in urine samples while there were significant differences in Pt concentrations of ultrafiltrate and whole plasma samples by the two methods. Discussion of possible reasons for these differences emphasizes the need for future critical evaluation of these methods. PMID- 8489006 TI - The ionophore ETH 129 as Ca2+ translocator in artificial and natural membranes. AB - We have investigated the ability of the neutral ionophore ETH 129 to translocate Ca2+ across artificial and biological membranes. ETH 129 induces Ca2+ transport across planar lipid bilayer. The zero-current membrane potential in a gradient of Ca2+ concentration exhibits Nernst behavior. The dependence of the membrane conductance on ionophore and Ca2+ concentration indicates that three ionophore molecules are needed to transfer one Ca2+ across the hydrophobic region of the membrane. In mitochondria the neutral Ca2+ ionophore can move Ca2+ inside in response to a negative membrane potential under conditions in which the endogenous uniporter is blocked by ruthenium red. This electrophoretic transport of Ca2+ by ETH 129 occurs at a concentration much lower than the one previously reported with the neutral Ca2+ ionophore ETH 1001. Using sea urchin eggs, we have also shown that the efficiency of ETH 129 in inducing egg activation, as revealed by cortical granules exocytosis, is four orders of magnitude higher than that of the commonly used Ca2+ ionophore A21387. ETH 129 is a very efficient and useful tool for use in the investigation of Ca(2+)-dependent biological processes. PMID- 8489007 TI - Use of in vivo 13C nuclear magnetic resonance spectroscopy to follow sugar uptake in Zymomonas mobilis. AB - A noninvasive, in situ, in vivo, and anomer-specific method for studying membrane transport of sugars in bacteria is presented. High-resolution 13C NMR was used to measure the distribution of alpha- and beta-xylose, maltose, Mes buffer, and ethanol in the extracellular and the cytoplasmic compartments in dense cell suspensions of Zymomonas mobilis, an aerotolerant bacterium that transports xylose but does not further metabolize it. The method relied on a difference in the magnetic susceptibility of the media inside and outside cells, induced with Dy-diethylenetriaminepentaacetic acid. The applicability of this method was demonstrated: (a) by showing that xylose and ethanol crossed the inner membrane of Z. mobilis while maltose and Mes buffer did not and (b) by a kinetic study of xylose uptake in this organism. After addition of xylose, both the extracellular decrease in the alpha- and beta-anomers in the medium and their intracellular accumulation could be followed. PMID- 8489009 TI - Micromethod for the determination of heparin in plasma after intravenous and subcutaneous administration. AB - A sensitive method has been developed for extracting and analyzing heparin from plasma after intravenous and subcutaneous administration in humans and rabbits. The glycosaminoglycans are precipitated from the biological fluid as cetylpyridinium salt, and heparin is cleaved with heparinase. The reaction products are analyzed by polyacrylamide gel electrophoresis and visualized by staining with Azure A/ammoniacal silver. With this method 12 ng of heparin can be detected. PMID- 8489008 TI - Stoichiometric labeling of peptides by iodination on tyrosyl or histidyl residues. AB - Radioiodination with 125I or 131I is a favored technique for labeling biologically active peptides or proteins because of high specific radioactivities and convenience in counting gamma-emissions. Previous studies used trace labeling, in which fewer than 1% of the molecules are iodinated. We describe procedures for obtaining stoichiometrically iodinated and therefore chemically homogeneous peptides with specific activities exceeding 10(7) cpm/micrograms (approximately 10 Ci/mmol). By analyzing the pH dependence of iodination on tyrosyl and histidyl residues, we show that the method described can be applied to many short peptides and optimized for labeling on tyrosine and/or histidine. The power of reverse-phase HPLC is exploited to resolve multiple products substituted with different molar equivalents of iodine from each other and from unlabeled peptide. Specific radioactivity ratios can be used to identify the products, as confirmed by Edman sequence analysis under conditions that separate iodinated tyrosine and histidine derivatives from all other amino acids. We also show that the biological activities of iodinated and uniodinated peptides can differ by several orders of magnitude in a T cell assay and demonstrate the usefulness of stoichiometric labeling to overcome ambiguities inherent in studying biological activities with trace-labeled peptides. PMID- 8489010 TI - Defined analyte-enzyme conjugates as signal generators in immunoassays. AB - We investigated the synthesis of progesterone-horseradish peroxidase (P-HRP) conjugates and products purified by affinity chromatography. The obtained preparations were characterized with an immobilized monoclonal antibody in solid phase immunoassays. Three homogeneous P-HRP conjugates were isolated. Two preparations were identified to contain a single progesterone ligand on the enzyme molecule. A third preparation contained two progesterone ligands. We postulate that conjugation can occur at two different positions on the enzyme, and that the different microenvironment of the protein structure surrounding the ligand contributes to different binding constants of the conjugates with immunoglobulin. By comparing the effective binding constants derived from affinity chromatography and from Scatchard analysis, we have demonstrated that the divalent conjugate binds to antibody immobilized on planar surfaces only by a single attachment due to steric restriction. Dose-response curves for progesterone using the isolated P-HRP conjugates have been investigated and compared. PMID- 8489011 TI - Protease activity and autodigestion (autolysis) assays using Coomassie blue dye binding. AB - A new proteolytic assay is described involving Coomassie blue. Under specified conditions, the amount of Coomassie-stained casein protein hydrolyzed by several proteases was proportional to the amount of protease. Coomassie dye reaction was used directly to determine the change in protein concentration of the substrate casein during proteolysis by three proteases: stem bromelain, papain, and trypsin. This method can be used with 0.1- to 0.5-micrograms quantities of protease. The dye reagent was used directly on the protease protein in order to obtain an assay of autodigestion. Autodigestion of bromelain at 50 and 25 degrees C was followed by measuring the amount of residual protease protein with time. PMID- 8489012 TI - Two methods for the introduction of amino groups into agarose-based matrices: their use in immunoaffinity chromatography. AB - In this study two methods of coupling antibody to Sepharose CL2B are described. They involve the introduction of amino groups either via an amino acid such as glycine or through polyethyleneimine. After introduction of amino groups into the matrices, their activation and simultaneous fixing were accomplished by treatment with glutaraldehyde. Monoclonal antibody raised against von Willebrand factor was used as a model ligand to demonstrate the stability and performance of the affinity supports. Both methods examined in this study resulted in good retention of the antibody's binding capabilities and excellent stability of the derivatized matrices. Leaching of the insolubilized protein was considerably less with the polyethyleneimine-glutaraldehyde than with cyanogen bromide. PMID- 8489013 TI - Large-scale sequencing library production: an adaptor-based strategy. AB - A significant bottleneck in large-scale DNA sequencing projects is the creation of high-quality random libraries suitable for sequencing. We have utilized an adaptor-based strategy and developed a simple protocol to reliably generate single-insert random subclone M13 libraries yielding uniform coverage and > 10(3) clones per microgram of DNA. Of the resulting white plaques, 95% contained inserts, < 0.5% were due to adaptors with no insert, and none of the clones were found to contain extraneous DNA (0/600) or multiple inserts (0/300). PMID- 8489014 TI - Activation of protein kinase C in vitro and in intact cells or synaptosomes determined by acetic acid extraction of MARCKS. AB - MARCKS is a widespread cellular phosphoprotein that migrates at 80-87 kDa on polyacrylamide gels. It is phosphorylated apparently exclusively by protein kinase C (PKC) and its phosphorylation in intact cells can be used as an index of intracellular PKC activation. Most methods for the determination of its phosphorylation state in vitro or in intact cells rely on two-dimensional gel electrophoresis to detect the protein with a pI of 4.6; however, this does not readily allow for multiple samples to be simultaneously and rapidly processed. Here we utilize the acid solubility of MARCKS to develop a novel extraction procedure. MARCKS was found to be soluble in 40% acetic acid and can be extracted quantitatively and rapidly from phosphorylation mixtures in vitro or from labeled intact cells. Acetic acid has the advantage that it is volatile and readily removed and precipitates protein in the presence of SDS, and the extracted protein is more readily resuspended in sodium dodecyl sulfate (SDS) sample buffer. Two extraction methods were developed, one for extraction of MARCKS from [gamma-32P]ATP-labeled subcellular fractions or intact synaptosomes labeled with 32Pi and one for extraction from 32Pi-labeled cultured nucleated cells, the latter requiring an additional protein recovery and DNA removal step. With this procedure MARCKS phosphorylation in intact synaptosomes was shown to be reversibly stimulated upon depolarization and MARCKS phosphorylation was found to be an early event in the activation of cultured smooth muscle cells by angiotensin II. PMID- 8489015 TI - Solubilization and purification of enzymatically active glutathione S-transferase (pGEX) fusion proteins. AB - The pGEX glutathione S-transferase (GST) fusion protein system is used extensively for high level expression and rapid purification of fusion proteins from bacterial and eukaryotic cell lysates. Unfortunately, many GST fusion proteins are partially or completely insoluble, and thus cannot be purified efficiently from a crude lysate. We have adapted a protocol, previously used to solubilize actin, for the purification of otherwise insoluble GST fusion proteins. Using a GST fusion of the nontransmembrane protein tyrosine phosphatase 1B, we demonstrate that tyrosine phosphatase enzymatic activity is maintained during the purification process. We provide methods for the purification of GST fusion proteins at analytical and preparative scales, and demonstrate that saturation of glutathione agarose is dependent on fusion protein molecular weight. Finally, we present strategies for eluting purified fusion proteins from glutathione agarose beads, for storing eluted protein, and for preparing covalently coupled affinity matrices. PMID- 8489016 TI - A polymerase chain reaction-based method for detection and quantification of reporter gene expression in transient transfection assays. AB - Transcription in higher eukaryotes is often studied by the use of transient transfection assays. These experiments are performed by cloning putative cis acting transcriptional elements (i.e., a promoter or enhancer) with a reporter gene that codes for a protein not expressed by the target cells. Although this approach is useful in many cases, the limited sensitivity of reporter assays can prevent studies in cases where few cells are obtainable or efficiency of transfection is low. We present an alternative approach. Cells are transfected with a plasmid containing a promoter with a human growth hormone (hGH) reporter gene. After an incubation period, RNA is isolated, and DNA complementary to the growth hormone mRNA is produced. The reporter cDNA concentration is measured by quantitative polymerase chain reaction (PCR). We have designed PCR primers that span the mRNA splice sites of the human growth hormone gene; these ensure exclusive amplification of the hGH cDNA and not the reporter plasmid. The assay is sensitive and simple to perform, requires no special equipment, and can quantify reporter cDNA concentration over a broad range. PMID- 8489017 TI - A rapid spectrophotometric estimation of individual phosphates and phosphonates: its application to chromatography of sugar phosphates and their phosphonate analogues. AB - A compound containing the -PO3H2 group (phosphoric acid, one of its monoesters, or an alkylphosphonic acid) may be rapidly assayed by the decrease it produces in the absorbance at 450 nm of a buffered acidic solution of Fe3+ and N(-3) [corrected]. The method has been used to follow chromatograms of sugar phosphates and their phosphonomethyl analogues. PMID- 8489018 TI - Coulometric electrochemical detection of hydroxyproline using 7-chloro-4 nitrobenzo-2-oxa-1,3-diazole. AB - A new method for detection of hydroxyproline has been developed. Hydroxyproline was derivatized using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole; separation and detection were accomplished using HPLC with coulometric electrochemical detection. Derivatized hydroxyproline was initially detected using a 16 channel coulometric electrochemical array system. The assay was slightly modified for use with a simpler 2-channel coulometric electrochemical detector. Both detectors are sensitive into the upper fmol range. Derivatization of hydroxyproline occurs in 5 min and the derivative is stable for several hours at 0 degrees C. The techniques were used to quantitate hydroxyproline in purified type I collagen and other biological samples. PMID- 8489019 TI - On-line membrane blotting of peptides and proteins from a capillary column. PMID- 8489020 TI - Detection of strand-specific DNA-protein interactions using single-stranded PCR products. PMID- 8489021 TI - Electroporation of the HIV Tat trans-activator protein into cells. PMID- 8489022 TI - Flow-cytometric measurement of histone H1o in human cells. PMID- 8489023 TI - Identification of cysteine residues alkylated with 3-bromopropylamine by protein sequence analysis. AB - A new reagent for the routine identification of cysteine residues during protein sequencing is described. This method employs 3-bromopropylamine to alkylate cysteines in proteins after reduction with dithiothreitol. Upon sequencing of the protein on an Applied Biosystems 477A protein sequencer, the aminopropylcysteine residue yields a phenylthiohydantoin (PTH) derivative which elutes reproducibly at a unique position immediately after PTH-leucine; baseline resolution is achieved without modification of the PTH analyzer gradient. Unlike PTH pyridylethylcysteine, the relative elution position of the aminopropylcysteine PTH derivative is not affected by changes in the ionic strength of the analyzer solvents. In addition, the previewing of the next amino acid which is observed in proteins modified with 4-vinylpyridine does not occur in aminopropylated proteins. Preparation of alkylated proteins for electroblotting onto polyvinylidene difluoride (PVDF) membranes and methods for desalting alkylated proteins immobilized on precoated glass fiber filters or PVDF membranes are also described. PMID- 8489024 TI - Modification of a competitive protein binding assay for determination of inositol 1,4,5-trisphosphate. AB - A modification of a competitive protein-binding method for the determination of inositol 1,4,5-triphosphate (Ins(1,4,5)P3), facilitated by the use of a cell harvester, is described. The method is based on the competition of [3H]Ins(1,4,5)P3 with Ins(1,4,5)P3 in the sample for binding to a binding protein prepared from bovine adrenal cortex. The assay is carried out in 96-well microtiter plates in a final volume of 100 microliters and free [3H]Ins(1,4,5)P3 is separated from bound by filtration using a cell harvester. This allows the rapid measurement of large numbers of samples, with high reproducibility. Ins(1,4,5)P3 bound to a single class of high-affinity receptors with a KD of 2.3 +/- 0.2 nM and a Bmax of 289 +/- 7 fmol/mg of protein. The binding was rapid, reaching equilibrium after 20 min, and reversible. The sensitivity of the assay allows the determination of amounts of Ins(1,4,5)P3 as small as 0.1 pmol, which corresponds to a concentration of 5 nM in the sample. The application of the method to measure the formation of Ins(1,4,5)P3 in DDT1 MF-2 smooth muscle cells activated with ATP or bradykinin is described. The modification is a rapid, sensitive, convenient, and relatively inexpensive method for the determination of Ins(1,4,5)P3 in large numbers of samples. PMID- 8489025 TI - Continuous spectrophotometric assay for ascorbate oxidase based on a novel chromophoric substrate, 2-aminoascorbic acid. AB - Recently, we reported the development of a sensitive continuous spectrophotometric assay for the ascorbate-dependent mammalian enzyme dopamine beta-monooxygenase based on the novel chromophoric electron donor 2-aminoascorbic acid [K. Wimalasena and D.S. Wimalasena (1991) Anal. Biochem. 197, 353-361]. We now report that ascorbate oxidase (EC 1.10.3.3, L-ascorbate:O2 oxidoreductase) also catalyzes the oxidation of 2-aminoascorbic acid to chromophoric 2,2' nitrilodi-2(2')-deoxy-L-ascorbic acid (red pigment). The reaction is kinetically well behaved, displaying the expected stoichiometry for an oxidase-catalyzed reaction with respect to oxygen and the oxidation product (red pigment), demonstrating that 2-aminoascorbic acid is a well-behaved alternative substrate for the enzyme. Ascorbate oxidase is a very efficient enzyme toward its natural substrate, ascorbic acid. Although 2-amino-ascorbic acid is a significantly weak substrate for the enzyme in comparison to ascorbic acid, as indicated by the apparent initial rate kinetic parameters, the high extinction coefficient of the red pigment under our assay conditions suggests that this novel reactivity of the enzyme could be used to design a sensitive, convenient, and continuous spectrophotometric assay for ascorbate oxidase. While this assay is more convenient than the existing oxygen monitor assay, its adaptability to measure the activity of the enzyme in the immobilized form may be helpful in the development of technologies for the automated detection of ascorbic acid in biological fluids for industrial or clinical applications. In addition, this novel reactivity of the enzyme may be used to examine the substrate specificity and the mechanism of action of the enzyme. PMID- 8489026 TI - Use of carboxyatractylate and tight-binding inhibitor theory to determine the concentration of functional mitochondrial adenine nucleotide translocators in a reconstituted system. AB - The adenine nucleotide translocator (AdNT) has been isolated from rat heart mitochondria and reconstituted into liposomes containing ATP. Translocator activity was determined using a coupled enzyme system to measure the ADP-induced efflux of ATP from the liposomes. In order to determine specific activity, the number of functional translocators must also be known. Carboxyatractylate (CAT) is a highly selective inhibitor of the AdNT, with Ki < 10 nM, a value sufficiently low relative to the concentration of protein in transport assays to suggest the use of tight-binding inhibitor theory to quantify functional translocators. Ackermann-Potter plots of velocity vs proteoliposome concentration at several different CAT concentrations were used both to demonstrate the occurrence of tight-binding inhibition and to determine the concentration of AdNT catalytic sites in the native orientation. The results obtained agreed well with earlier reports based on [14C]CAT binding; functionally reconstituted AdNT represented 5-10% of the protein added to the system. Specific activities were ca. 7-10 mumol/min mg depending on the lipid composition of the liposomes. Unincorporated protein did not appreciably affect the measurements. This methodology should be readily applicable to any reconstituted systems for which high-affinity inhibitors which bind only to active protein are known. PMID- 8489027 TI - Application of 13C-labeling and nuclear magnetic resonance spectroscopy to pharmacokinetic research: measurement of metabolic rate of benzoic acid to hippuric acid in the rat. AB - The use of 13C-labeling and nuclear magnetic resonance (NMR) spectroscopy to trace the biotransformation of benzoic acid (BA) to hippuric acid (HA) in the rat has been described. Novel [2,4,6,7-13C4]BA, which was labeled in the specific protonated carbons, was used in order to enhance the sensitivity of 13C NMR detection on the basis of the nuclear Overhauser enhancement and short spin lattice relaxation time. The urinary excretion of [2,4,6,7-13C4]HA formed from intravenously administered [2,4,6,7-13C4]BA was followed by proton-decoupled 13C NMR spectroscopy (only 10 min accumulation time) without any separation procedures such as extraction and chromatography, using [2-13C]sodium acetate as an internal standard for quantitation. The heights of resonances for C2,6 of [2,4,6,7-13C4]HA and C2 of the internal standard were used to calculate [2,4,6,7 13C4]HA concentration. The lower limit of measurable amounts (ca. 40 nmol) was found to be improved about one order of magnitude over that of the method using commercially available [7-13C]BA. In general, this tracer technique has the potential for wide application to pharmacokinetic research since xenobiotic and endogenous metabolism can be followed by very simple and convenient procedures. PMID- 8489028 TI - Improvements in the numerical analysis of thermodynamic data from biomolecular complexes. AB - In this work, recent improvements in the capability of the numerical solver-based binding data global analysis program, BIOEQS, are presented. These improvements represent an expansion of the types of physical models which can be considered. The first realm of improvement concerns the modeling of systems which include several species of the same stoichiometry and differing chemical potentials, or site isomers. Such an option is generally used in the analysis of binding of multiple ligands to multiple protein sites. In addition to classical ligand binding problems, such a capability is useful in considering the binding of protein to different sites on the same DNA molecule and the effects of ligation upon these equilibria. It can also be employed for consideration of the equilibrium unfolding of oligomeric proteins with folded monomeric intermediates. The effect of dilution of the protein and ligation by up to two different types of ligands at multiple binding sites upon the dissociation and unfolding properties of the oligomers is now possible. The second advance which has been incorporated into the modeling capabilities of the BIOEQS program is the option of considering perturbations to the multiple binding or folding equilibria by chemical denaturants, temperature, or high hydrostatic pressure. Additional improvements to the BIOEQS program include direct mapping of individual species or sums of species to the numerical physical experimental observable. The values of the observable corresponding to particular species or to 0 and 100% completion of a titration can be either fixed or floating parameters in the fit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489029 TI - [In memoriam Reinhold Sulzmann]. PMID- 8489030 TI - A scanning electron microscopic and immunohistochemical study of spinal ligaments innervation. AB - Neural elements in the interspinous and longitudinal ligaments of the human lumbar spine were investigated by means of scanning electron microscopy (SEM) and immunohistochemistry for neurofilament protein (NFP). The SEM results agree with our previous findings of nerve fibers and localized them in the superficial layers of the ligaments as well as in the deeper ligamentous substance. The immunohistochemical staining for NFP has clearly confirmed the presence of sensory nerve endings. Most of the nerve fibers terminated as simple free endings which are thought to be nociceptors. PMID- 8489031 TI - An anatomical study of the laterotrigeminal venous system. AB - The middle cranial fossa of 100 cadavers were dissected under stereoscopic loupe in order to identify and systematize the venous vessels located along the lateral margin of the trigeminal cave. The author found that at the sensitive root and trigeminal ganglion level a dural venous canal was present in most individuals examined and that the upper side of this canal communicated with the superior petrosal sinus. However, at the level of the lateral border of the intracranial segment of the mandibular nerve, venous lacunae were found to prevail, and these lacunae communicated with several other venous formations in the peritrigeminal region. The author concludes that the venous vascularization of this area constitutes a major risk in surgical interventions made in the middle cranial fossa. In addition, it is a relevant factor in the hemodynamics of the intracranial circulation. PMID- 8489032 TI - Histomorphometric analysis of the abomasum of the sheep during development. AB - Histomorphometric analyses were carried out on 64 embryos and fetuses and on 20 sheep (early postnatal to adult age). Histodifferentiation of the abomasum took place at 33 days of fetal life, with the appearance of abomasal villi at 53 days. By 64 fetal days, the epithelium had changed from pseudostratified to simple mucous cylindrical. Acidic glycoproteins appeared at 46 fetal days. Neutral glycoproteins did not appear until later stages of development, near birth. We believe that the configuration of a simple epithelium with acidic secretion is enhanced at birth by the secretion of neutral glycoproteins which act as a buffer against acidic substances, and particularly against the abomasal acidity during lactation. Growth curves and formulae were set out for each tissue layer. PMID- 8489033 TI - [The conjunctival epithelium of dogs. Light and electron microscopic investigations]. AB - The conjunctiva of the dog has a smooth surface on the inside of the upper and lower lid and of the bulbus oculi. In these areas the conjunctiva is covered by a stratified squamous epithelium, the polygonal surface cells of which have microvilli and microplicae which are different in number and show a great variety of shapes. In the passage towards the fornix conjunctivae a stratified cuboidal epithelium is to be discerned. In the fornix itself, the conjunctiva is arranged in small folds which are protruded by goblet cells and the openings of lacrimal glands. Here a stratified cuboidal or columnar epithelium can be observed which at the electron microscopic level shows in all epithelial layers--mostly however in the stratum superficiale--morphological signs of enhanced metabolic activities. The bulbar surface of the third eyelid which is covered by a stratified squamous epithelium has a three-dimensional moulded pattern of pads and grooves. The structure of the conjunctival epithelium to some extend is age dependent. PMID- 8489034 TI - Morphology of the rat uterus after long-term treatment with progesterone antagonists. AB - The effects of long-term treatment with the progesterone antagonists ZK 98.299 and ZK 112.993 on the uterus of intact mature rats were investigated with light and electron microscopy. After 3-4 weeks treatment with both progesterone antagonists, the uterine luminal epithelium showed ongoing mitotic activity, increased apoptosis and invasion by granulocytes. Many uteri showed metaplastic areas with stratified squamous epithelium. Basically, the same changes occurred, but to a lesser extent, in the glandular epithelium. At the ultrastructural level, the epithelial cells displayed the morphological features of a certain degree of differentiation. The dissociation of collagen fibres, infiltration by granulocytes and dilatation of small vessels were observed in the subepithelial connective tissue. The myometrium increased in thickness and electron microscopic examination revealed hypertrophic myocytes with a well developed granular endoplasmic reticulum. Most of the morphological reactions may be regarded as due to the direct inhibitory action of progesterone antagonists at the level of the different uterine tissues and the resulting unopposed action of estrogen. The metaplastic changes and the suppression of the anti-proliferative action of progesterone on uterine epithelial cells should be taken into account when treating women in their reproductive years with these drugs for long periods of time, as may be necessary for the endocrine treatment of mammary cancer and endometriosis. PMID- 8489035 TI - Histological examination of chick embryos with ocular hypoplasia. AB - From so-called "dead-in-pipped-eggs" provided by the Poultry Breeding Center of Gifu Prefecture, we obtained two chick embryos with hypoplastic eyes on external examination, and studied the visual system and cranial nerve nuclei innervating the extraocular muscles. The upper bills of both embryos deviated toward one side when observed with the naked eye. In histological sections from the most severely affected eyeball of each case primordial retinal tissue in the poorly developed orbit seemed to be at the stage of optic vesicle formation; it had not differentiated into individual layers. The optic nerve was absent from these eyeballs and the neural retina had multiple folds. The ciliary ganglion was smaller on the more severely affected side than on the contralateral side which had only mild hypoplasia. The optic nerve, which was present on the contralateral side, bifurcated at the level of the chiasma close to the diencephalic base; one branch ran toward the ipsilateral optic tectum and the other toward the contralateral brain region. The oculomotor and trochlear nerve nuclei could be identified bilaterally in one of the embryonic brains but not in the other. These findings suggest that hypoplasia of the neural retina and optic nerve in an orbit leads to bifurcation of the contralateral optic nerve which, under normal conditions, should completely cross at the chiasma. This may also suggest that retinal afferents from the brain are also affected in the hypoplastic eyeball. PMID- 8489036 TI - Morphological changes in thrombocytes during blood bank storage. An ultrastructural morphometric study. AB - Monitoring the storage lesion of platelet concentrates (PC) is commonly done by determining metabolic parameters, release of cytoplasmic markers and granules contents and watching the light microscopical appearance of platelets. Descriptions of ultrastructural changes are rare, and so we ascertained the changes in two important organelles, the alpha- and lysosomal granules and the open canalicular system (OCS), by morphometric analysis. Single donor PC's were prepared with a CS-3000 plus (Baxter) processor and stored under routine conditions. The volume fraction of the granules displayed a decrease to 43% after 8 days of storage, and the OCS fraction increased to 143%. Moreover, changes in the morphology of granules and the development of OCS channels are described, and ballooning and even complete lysis of some platelets could be observed after only three days. Furthermore, the membrane flux in the formation of pseudopodia is discussed. Our results stress the need to establish better preparation and storage conditions for platelet concentrates. PMID- 8489037 TI - Pars tuberalis specific cells within the pars distalis of the adenohypophysis. An ontogenetic study. AB - Several types of secretory cells of the pars distalis (pd), especially gonadotrophs, are known to occur in the distal pars tuberalis (pt) of the rat. The distribution of the pt-specific cells, however, within the pd has not been investigated in detail and is the subject of this study. Pt and pd of the rat adenohypophysis were investigated at different stages of the peri- and postnatal development by light and electron microscopy using conventional and immunohistochemical staining. The distribution of pt-specific cells changes from a continuous strand of cells extending on the ventral surface to the centre of the pd perinatally to single clusters in the vicinity of the big portal vessels in adult rats. The secretory activity of pt-specific cells within the pd also varies with age. It is highest perinatally, declines in the young rat, and increases again in the adult animal. Functional implications of our observations are discussed especially in relation to the distribution of melatonin-binding pituitary cells. PMID- 8489038 TI - [Microstructure of fossil mammalian bones from the Rixdorfer Horizon of Weichsel Kaltzeit at Niederlehme near Konigs Wusterhausen (Brandengurg)]. AB - The structure is reported of bones of glacial-period mammals, which were found in 1973 to 1989 in gravel-sandy soil of the fossiliferous layer "Rixdorfer Horizont" at Niederlehme near Konigs Wusterhausen. The findings, probably, date from one of the interstages of the glacial period "Weichsel-Kaltzeit" before the stage "Brandenburger Stadium". Their embedding took place more than 20,000 years ago. Changes of the deposit of bones and teeth from older sediments are not to exclude in the finding place Niederlehme. In the collection of findings with 102 skeletal parts are to define following species: Mammuthus primigenius, Coelodonta antiquitatis, Equus sp., Bison priscus, Megalocerus giganteus, Cervus elaphus, Rangifer tarandus and Canis lupus. A trajectorial direction of the trabecula in the substantia spongiosa is evident. There are also specific channels of blood vessels with different diameters. This channels have completely closed bone-wall (with a central venous sinus of diameter 5 to 10 mm) or in little vessels (diameter 1 to 3 mm), we have found many apertures to the rooms of the substantia spongiosa. The microscopical investigation of bones of Mammuthus primigenius has shown Havers' channels and perforating channels, Havers' systems and lacunae osseae. PMID- 8489039 TI - Structure on the capsular ligaments of the facet joints. AB - Microscopic studies showed that the capsular ligaments were mostly composed of collagenous tissue. The collagen fiber bundles were found to be crimped at right angles to their long axis. The collagen fibrils were connected transversely by proteoglycan filaments which were regularly associated with their periodicity. Among the collagen fiber bundles were varying quantities of elastic fibers and numerous fibroblasts. The highest concentration of elastic fibers was found in the posterior and inferior aspects of the capsular ligaments. These findings are discussed in relation to the mechanical behavior of the capsular ligaments. PMID- 8489040 TI - The effect of ageing on the posterior medial and posterior lateral subnuclei of the bed nucleus of the stria terminalis in the mouse. AB - The posterior medial and posterior lateral subnuclei of the bed nucleus of the stria terminalis were examined in male ASH/TO mice aged 6, 15, 25, 28 and 31 months using quantitative histological techniques. Neuron number in the posterior lateral subnucleus remained constant from 6 to 31 months (mean 1918 +/- 60) whereas in the posterior medial subnucleus neuron number fell from 5165 +/- 145 at 25 months to 4197 +/- 172 at 28 months. There was no further decrease in neuron number at 31 months (4034 +/- 55). PMID- 8489041 TI - EMG study of the anterior, superior and posterior auricular muscles in man. AB - Anterior, superior and posterior auricular muscles were studied electromyographically by means of wire electrodes. During ear movement the three muscles acted as a group and the movement was always directed upwards and backwards. The highest electrical activities were observed during natural smiling and yawning. Mouth opening without the drawing backwards of the comissura labiorum and the displacement of galea aponeurotica also produced electrical activity by the auricular muscles, with however, less intensity and in only 50% of the cases studied. PMID- 8489042 TI - A variant of the floor of the carotid canal. AB - 325 skulls were investigated in the present study. The absence of the floor of the carotid canal was found in only one skull, a condition which makes the internal carotid artery vulnerable during a surgical approach to this region. PMID- 8489043 TI - [The laterocranial fascia structures in the upper and forearm and the differences in the insertion of the M. biceps brachii in domestic mammals]. AB - The laterocranial fascia of the upper arm and forearm, as well as aponeurotic relationships of the Musculus biceps brachii were investigated on each of ten forelimbs from horses, cattle and swine. Ten canine biceps were also investigated. Equine and bovine fascia contain elastic components. An as-yet undescribed ligament-like aponeuroses of the laterocranial forearm fascia to the Fossa radialis humeri was seen in all three species studied. The laterocranial fascia of the upper and forearm form a common passage for the Musculi brachialis et extensor carpi radialis. In the case of the horse, the ulnar aponeurotic tendon of the biceps muscle crosses below the Ligamentum collaterale cubiti medialis. In cattle, on the other hand, it runs between the two branches of the collateral ligament, to attach on the olecranon. This portion of the equine tendon protrudes into the joint. It has connective tissue character in young animals, but becomes fibrocartilaginous in older horses. The radial aponeuroses of the canine biceps exhibits two branches. A situation similar to that seen for the ulnar aponeuroses of the equine Musculus biceps brachii is observed on the inside surface of the porcine Ligamentum cubiti mediale, in which a wedge of connective tissue protrudes into the joint, taking on fibrocartilaginous character in older animals. PMID- 8489044 TI - Radiographic study of postnatal development of the tarsus in west African dwarf goats. AB - Seven goats of the West African dwarf breeds, three females and four males, from the same farm were studied by serial radiography from the first week of life and at 3, 6, 9, 16, 23, 28, 37 and 46 weeks of age. The radiological appearance of the developing tarsus as evaluated from radiographs is described. During the first week postnatally, eight loci were observed to be partially ossified. The talus, tarsi centrale (Tc), first (T1), second (T2), third (T3) and fourth (T4) tarsal bones had each a single loci. The calcaneus bone had two loci, one for the tuber calcanei and another for the calcaneus himself. Fusion of the locus for T2 and T3 was evident in radiographs taken at three weeks. The fused T2 + T3 also appeared fused with the Tc in one of the goats at 23 weeks. The Tc and T4 were observed to fuse in only three of the goats at 23 weeks while in others the bones remained separate throughout the study period. In those goats where the Tc and T4 tarsal bones were not fused, the three tarsal joints were linked by a radiolucent line between these bones. While in the goat where Tc and T2 + T3 bone fusion has occurred the distal intertarsal joint was blocked and the proximal intertarsal was communicating with the tarsometatarsal joint between the separate Tc and T4. The tarsus of the goat is variable and differs from that of sheep and cattle. PMID- 8489045 TI - [Chronology of the postnatal ossification of the shoulder and elbow joints in the Siamese cat (Felis catus L.)]. AB - A study was done by radiological techniques to show the chronology of ossification of the shoulder and cubit joints in the Siam cat, from birth up to the 25th week of postnatal development. For this experiment we used 40 little cats (19 males and 21 females) belonging to 11 litters subjected to different controls: pattern race, healthy, feeding, growing up and radioactivity. The time of the appearance and the evolution of the ossification centers is determined as well as the phenomenon of fusion during this time. The postnatal ossification from both joints of the Siam cat is compared with that of the common cat. PMID- 8489046 TI - [Chronology of the postnatal ossification of the thoracic limb in the Siamese cat (Felis catus L.)]. AB - A study was done by radiological techniques to show the chronology of ossification of the thoracic autopodo of the Siam cat from birth up to the 25th week of postnatal development. For this experiment we used 40 little cats (19 males and 21 females) belonging to 11 litters subjected to different controls: pattern race, healthy, feeding, grow up and radioactivity. The time of the appearance and evolution of the centres that form the basipodo, metapodo and acropodo of the thoracic limb is determined. Likewise it is analyzed the phenomenon of fusion during that time to define the main ossification sequence in the carpo. The aspects of the postnatal ossification of the thoracic autopodo in the Siam cat are compared with the literature of different authors about the common cat. PMID- 8489047 TI - Histology and histomorphometry of the tibial diaphyseal growth in two turkey strains during the first six weeks after hatching. AB - The comparative cortical growth of the tibio-tarsus was studied during the first six weeks after hatching in two turkey strains, a light and a heavy one. At one day post-hatching the cortical appeared to be constituted in both strains of an embryonic non-active fibrous bone tissue which had completely disappeared at one week. On and after one week the cortex was constituted of a fibrolamellar adult bone tissue elaborated on the periosteal part of the cortex. Its vascular pattern depended on the strain and on the thickness of the cortical faces. The histomorphometric studies showed that the growth in thickness was earlier and faster in the heavy strain with a Total Diaphyseal Surface twice larger at 6 weeks but a Diaphyseal Cortical Ratio not significantly different since 3 weeks of age. PMID- 8489048 TI - [The innervation of the syrinx of the duck (Anas platyrhynchos)]. AB - The innervation of the Syrinx was studied in 15 female Peking Ducks of 10 to 12 months old by using L.M. and E.M. In this organ a nervous plexiform net is present located in the connective below the epithelium along the membrana tympaniformis medialis. This net-work is made of the nervous trunks which repeatedly anastomise among themselves and display during their course acapsulate ganglions. However, no specialized contact device were encountered at the periphery. PMID- 8489049 TI - Loads on muscles, tendons and bones in the hind extremities of sheep--a theoretical study. AB - Muscle forces and bending moments were calculated with a two-dimensional non linear force and moment analysis (according to the Finite Element Method) during the foot-lowering phase, stance phase and stem phase in the hind legs of sheep. During the foot-lowering phase, the largest production of force is detectable in the m. biceps femoris and the highest bending moment in the proximal third of the metatarsal bone. The lowest influence of force resulted during the stance phase. During the stance phase, high forces are detectable only in the patellar ligament and middle-high forces in the m. flexor digitalis profundus. In contrast, bending forces are almost equal in strength in the metatarsus and tibia. The strongest forces are detectable in the m. quadriceps femoris and extreme demands of the patellar ligament as well as of the flexors in the proximal ankle joint during the stem phase. PMID- 8489050 TI - Lectin histochemistry of glycoconjugates in horse salivary glands. AB - The glycoconjugate content of major horse salivary glands was investigated by means of horseradish peroxidase-conjugated lectins. Qualitative differences were observed in the terminal sugar residues of secretory glycoproteins and glycoconjugates linked to the apical surface of excretory duct epithelial cells. Mucous acinar cells in mandibular and sublingual glands contained oligosaccharides with D-galactose, alpha- and beta-N-acetylgalactosamine, N acetylglucosamine and fucose residues, whereas mandibular, sublingual and parotid serous cells contained only oligosaccharides with terminal alpha- and beta-N acetylgalactosamine residues. The apical portion of striated and interlobular duct lining cells of mandibular and sublingual glands stained for alpha- and beta N-acetylgalactosamine and for N-acetylglucosamine. In parotid gland the cytoplasm of intercalated duct cells and the apical surface of striated duct epithelial cells stained for alpha-N-acetylgalactosamine. PMID- 8489051 TI - [Radiological study of the sternum of the growing sheep]. AB - A radiological investigation of the sternum of the sheep demonstrated distinct growth phases. Forty Merino sheep of mixed breeds were distributed into 4 age groups of 0, 45, 105 and 270 days. Each animal was radiographed in sternal and lateral recumbency. Measurements were made from the radiographs. The sternebrae are rectangular in newborn and become concave in adult. The curvature of the sternum is 16 to 17 degrees at day 0 and 27-28 degrees at day 270. The nucleus of ossification was seen in all sternebrae at 45 days of age, they were present only in the most caudal sternebrae at 105 days. PMID- 8489052 TI - American Association of Anatomists 106th annual meeting held jointly with the Japanese Association of Anatomists. San Diego, California, March 27-31, 1993. Abstracts. PMID- 8489053 TI - Neurologic changes during carotid endarterectomy under cervical block predict a high risk of postoperative stroke. AB - BACKGROUND: This study was undertaken to confirm a previous report that patients having neurologic changes with carotid artery clamping were at greater risk of developing permanent postoperative neurologic complications after carotid endarterectomy. METHODS: Superficial and deep cervical plexus blocks were performed in 389 patients undergoing carotid endarterectomy. The patients were premedicated and sedated to a level that allowed awake neurologic assessment. Intraoperative neurologic changes were recorded and all patients were examined postoperatively by an independent anesthesiologist to record postoperative neurologic outcome. RESULTS: Trial carotid artery cross clamping resulted in 24% of patients having neurologic changes that usually responded to declamping and shunt insertion. Postoperative permanent neurologic complications occurred in 2.6% of patients, but were more common in patients who had neurologic changes associated with carotid artery cross clamping (6.6% compared to 1.1%, P < 0.01). Thrombosis of the carotid artery was the most common finding in patients who underwent reexploration of the carotid artery after developing postoperative neurologic changes. CONCLUSIONS: This study confirms that patients undergoing carotid endarterectomy under cervical plexus block who have intraoperative neurologic changes have a sixfold increase in the chance of developing a postoperative stroke. This high-risk group may benefit from antithrombotic therapies to improve their outcome. PMID- 8489054 TI - Effect of phenylephrine bolus administration on global left ventricular function in patients with coronary artery disease and patients with valvular aortic stenosis. AB - BACKGROUND: Although phenylephrine bolus administration is frequently used to increase coronary perfusion pressure in patients with coronary artery disease or valvular aortic stenosis, there are no data describing its effect on left ventricular function (LVF). METHODS: Twenty patients scheduled for elective coronary artery bypass grafting (group 1) and 18 patients scheduled for elective aortic valve replacement (group 2) entered the study. The effect of phenylephrine was compared with that of norepinephrine in those patients who developed a defined degree of arterial hypotension under general anesthesia. These patients were randomized to receive an initial bolus of either phenylephrine (1 micrograms/kg) or norepinephrine (0.05 micrograms/kg) followed by a bolus of the other drug after arterial pressure and heart rate (HR) had returned to baseline. Transesophageal echocardiography was used to evaluate LVF. Arterial pressure, HR, ejection time, and LV diameter, area, and wall thickness were recorded immediately before and for 3 min after bolus administration. Fractional diameter shortening, fractional area change, mean heart rate corrected velocity of circumferential fiber shortening (mVcfc), and LV meridional end-systolic wall stress (ESWS) were calculated. RESULTS: Both substances effectively restored arterial pressure in both groups. However, in group 1, phenylephrine administration resulted in a reduction of fractional area change from 0.51 (median) to 0.39 (P = 0.0007) and a reduction of mVcfc from 1.16 to 0.61 circ/s (P = 0.0001). End-systolic wall stress increased from 98 to 186 10(3) dyne-cm-2 (P = 0.0001). Administration of norepinephrine to group 1 and administration of either substance to the group 2 patients did not cause any significant changes of LVF. CONCLUSIONS: The results indicate that phenylephrine given as an intravenous bolus to patients with CAD anesthetized with fentanyl causes a transient impairment of LV global function and that phenylephrine bolus administration is well tolerated in patients with valvular aortic stenosis. PMID- 8489055 TI - Plasma concentration of fentanyl, with 70% nitrous oxide, to prevent movement at skin incision. AB - BACKGROUND: The Cp50 (minimal steady state plasma concentration of an intravenous analgesic/anesthetic required to prevent a somatic response in 50% of patients following skin incision) and the Cp50-BAR (minimal plasma concentration of an analgesic/anesthetic required to prevent either a somatic, hemodynamic, or autonomic response in 50% of patients following skin incision) have been recently proposed as a measure, like minimum alveolar concentration (MAC; and MAC-BAR), to establish the relative potency of intravenous analgesics. This study was conducted to establish the Cp50 for fentanyl. METHODS: Unpremedicated patients were administered fentanyl (in the presence of 70% N2O) via computer-assisted continuous infusion, a pharmacokinetic model-driven infusion device. After induction of anesthesia with fentanyl, the randomized target fentanyl concentration was entered into computer-assisted continuous infusion. This target fentanyl concentration was maintained until skin incision. Before induction, prior to skin incision, and immediately after skin incision, arterial blood samples were obtained for measurement of fentanyl and norepinephrine concentrations. At skin incision, patients were observed for a somatic, hemodynamic, or autonomic response. Only patients in whom the pre- and postincision fentanyl concentrations were within +/- 30% were included in the calculation of the Cp50. The Cp50 was calculated using logistic regression. RESULTS: The Cp50 for fentanyl was 3.26 ng/ml, and the Cp50-BAR was 4.17 ng/ml. CONCLUSIONS: Comparing these results with the previously published Cp50 of alfentanil, the potency of fentanyl relative to alfentanil is 1:58. Establishing the Cp50, once effect site equilibration has occurred, will allow pharmacodynamic comparisons between the opioids at equipotent concentrations. PMID- 8489056 TI - Improved noninvasive diagnostic testing for malignant hyperthermia susceptibility from a combination of metabolites determined in vivo with 31P-magnetic resonance spectroscopy. AB - BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P-MRS) in vivo has been suggested recently as a possible noninvasive diagnostic test in malignant hyperthermia (MH) susceptibility. However, differences between protocols and also within subjects may have led to inconsistent MRS abnormalities reported during and after exercise. The aim of the current study was to detect discriminant abnormalities in the leg muscles using in vivo 31P-MRS during the rest period. METHODS: Fourteen patients shown to be MH-susceptible and 22 patients MH-negative on the basis of in vitro caffeine/halothane contracture tests according to the European MH group protocol were compared to 36 control subjects using in vivo 31P MRS during the rest period. A score of MRS combined abnormalities was calculated from a stepwise discriminant function analysis. RESULTS: The MH-susceptible group had a significantly (P < 0.01) higher inorganic phosphate (Pi) to phosphocreatine (PCr) (Pi/PCr) value (0.134 +/- 0.022) than either the MH-negative (0.097 +/- 0.016) or the control (0.101 +/- 0.017) group. The MH-susceptible group also exhibited a significantly (P < 0.01) higher phosphodiesters (PDE) to PCr (PDE/PCr) value (0.093 +/- 0.056) than either the MH-negative (0.034 +/- 0.021) or the control (0.029 +/- 0.019) group. Combining both MRS parameters, 13 of the 14 MH-susceptible patients demonstrated abnormal MRS test results (score value < 1.65). Conversely, 21 of the 22 MH-negative patients had normal MRS results (score value > or = 1.65). The sensitivity and specificity of this threshold value were 93 and 95%, respectively. CONCLUSIONS: This study confirms that 31P MRS could be useful for distinguishing noninvasively between MH-susceptible and MH-negative patients if several MRS parameter are combined. Moreover, the present MRS approach appears to be more reliable and easier than that used during exercise. PMID- 8489057 TI - Leg heat content continues to decrease during the core temperature plateau in humans anesthetized with isoflurane. AB - BACKGROUND: Sufficient hypothermia during anesthesia provokes thermoregulatory responses, but the clinical significance of these responses remains unknown. Nonshivering thermogenesis does not increase metabolic heat production in anesthetized adults. Vasoconstriction reduces cutaneous heat loss, but the initial decrease appears insufficient to cause a thermal steady state (heat production equaling heat loss). Accordingly, the authors tested the hypotheses that: 1) thermoregulatory vasoconstriction prevents further core hypothermia; and 2) the resulting stable core temperature is not a thermal steady state, but, instead, is accompanied for several hours by a continued reduction in body heat content. METHODS: Six healthy volunteers were anesthetized with isoflurane (0.8%) and paralyzed with vecuronium. Core hypothermia was induced by fan cooling, and continued for 3 h after vasoconstriction in the legs was detected. Leg heat content was calculated from six needle thermocouples and skin temperature, by integrating the resulting parabolic regression over volume. RESULTS: Core temperature decreased 1.0 +/- 0.2 degrees C in the 1 h before vasoconstriction, but only 0.4 +/- 0.3 degrees C in the subsequent 3 h. This temperature decrease, evenly distributed throughout the body, would reduce leg heat content 10 kcal. However, measured leg heat content decreased 49 +/- 18 kcal in the 3 h after vasoconstriction. CONCLUSIONS: These data thus indicate that thermoregulatory vasoconstriction produces a clinically important reduction in the rate of core cooling. This core temperature plateau resulted, at least in part, from sequestration of metabolic heat to the core which allowed core temperature to remain nearly constant, despite a continually decreasing body heat content. PMID- 8489058 TI - Isoflurane minimum alveolar concentration reduction by fentanyl. AB - BACKGROUND: Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. METHODS: Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. RESULTS: There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. CONCLUSIONS: Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies. PMID- 8489059 TI - Intrathecal sufentanil for labor analgesia. Effects of added epinephrine. AB - BACKGROUND: Intrathecal sufentanil has been found to provide profound analgesia during labor. Epinephrine, when added to various local anesthetic agents or opioids, may modify the analgesic profile and incidence of side effects. The authors sought to determine the effect of adding 0.2 mg epinephrine to 10 micrograms sufentanil when administered for analgesia during labor. METHODS: Forty women during active labor received 10 micrograms intrathecal sufentanil either with (n = 20) or without (n = 20) 0.2 mg epinephrine in a randomized, blinded fashion. A combined spinal-epidural technique was used in which a 25-G Whitacre spinal needle was passed through a standard 17-G epidural needle. After injection of the study drug, an epidural catheter was passed, but no local anesthetics were given. Analgesia was quantitated using visual analog scores, as well as time elapsed until first request for additional analgesia via the epidural catheter (0.25% bupivacaine). The incidence and severity of pruritus, nausea, and somnolence were assessed. RESULTS: The duration (median, range) of analgesia was 90 (40-310) min in the plain sufentanil group (SUF) and 90 (45-230) min in the sufentanil-epinephrine (SUF-EPI) group (P = NS). The onset of analgesia was rapid (within 5 min) in both groups and visual analog scores did not differ at any observation point between groups. The incidence of pruritus was 80% (16/20) in the SUF group, and 45% (9/20) in the SUF-EPI group (P = 0.05). Four patients in the SUF group rated the pruritus as severe versus none in the SUF-EPI groups (P = 0.05). Seven patients (35%) in the SUF-EPI group experienced nausea, versus none in the SUF group (P = 0.004). No patient developed hypotension, motor blockade, fetal heart rate abnormalities, excessive sedation, or postdural puncture headache. CONCLUSIONS: Intrathecal sufentanil 10 micrograms, both with and without epinephrine, provided rapid-onset, albeit short duration, analgesia during labor. Epinephrine did not prolong the duration of intrathecal sufentanil analgesia. The addition of epinephrine increased the incidence of nausea and decreased the incidence and severity of pruritus. PMID- 8489060 TI - Laparoscopy explosion hazards with nitrous oxide. AB - BACKGROUND: During laparoscopic surgery utilizing carbon dioxide as the insufflating agent, nitrous oxide will diffuse into the peritoneal cavity if it is used as part of the anesthetic. Bowel perforation and the subsequent release of volatile bowel gas could create a explosion hazard. METHODS: Two related studies were undertaken. The first quantified the transfer of nitrous oxide, over time, in 19 female patients undergoing laparoscopy. The second established the lower limits of flammability of a range of concentrations of methane and hydrogen diluted with nitrogen (simulated bowel gas) in a range of concentrations of nitrous oxide diluted with carbon dioxide (simulated peritoneal gas). RESULTS: The mean concentrations of N2O at 10, 20, and 30 min from the time of insufflation were 19.9 +/- 4.8%, 30.3 +/- 6.8%, and 36.1 +/- 6.9%, respectively. The maximum reported concentrations of methane and hydrogen in bowel gas are 56% and 69%, respectively. The concentration of nitrous oxide necessary to support combustion of 56% methane is approximately 47%. By contrast, the concentration of nitrous oxide needed to support combustion of 69% hydrogen is approximately 29%. CONCLUSIONS: The authors have shown that it is possible for nitrous oxide to reach concentrations in the peritoneal cavity that can support combustion of bowel gas. PMID- 8489061 TI - The effectiveness of pressure support ventilation for mechanical ventilatory support in children. AB - BACKGROUND: The rapid respiratory frequency of children may lead to patient ventilator asynchrony and increase the work of breathing during mechanical ventilation, and the use of a small endotracheal tube and a demand valve can further increase this work of breathing. Although pressure support ventilation (PSV) is well known to reduce the work of breathing in adults, there are no reports regarding clinical studies of PSV in children. Therefore, the effect of PSV on breathing patterns and the work of breathing in children was studied. METHODS: Six children (3-5 yr of age) were studied in the immediate postoperative period. Three levels of PSV, 0, 5, and 10 cmH2O, were employed. Airway pressure, flow, tidal volume, minute ventilation, and respiratory frequency were measured. To assess the work of breathing, the negative deflection of esophageal pressure (delta Pes) caused by inspiratory effort was measured. The inspiratory work of breathing was also estimated directly by measuring the esophageal pressure-volume loop using the Campbell technique. RESULTS: Although minute ventilation did not change with PSV, tidal volume increased and respiratory frequency decreased with increasing levels of PSV. The delta Pes decreased markedly from 8.9 cmH2O with PSV of 0 cmH2O to 5.7 cmH2O with PSV of 5 cmH2O and 2.7 cmH2O with PSV of 10 cmH2O. The mechanical work of breathing also decreased from 0.743 Joules/l with PSV of 0 cmH2O to 0.463 Joules/l with PSV of 5 cmH2O and 0.196 Joules/l with PSV of 10 cmH2O. CONCLUSIONS: It was concluded that PSV can effectively augment spontaneous breathing and reduce the work of breathing in children. PMID- 8489062 TI - Transmucosal administration of midazolam for premedication of pediatric patients. Comparison of the nasal and sublingual routes. AB - BACKGROUND: Nasal transmucosal midazolam is effective for premedication of pediatric patients; however, 61-74% of these patients cry at nasal drug administration. Sublingual benzodiazepines, including midazolam, are effective in adults. The current blinded randomized study compared acceptance of and behavioral responses to transmucosal midazolam administered via the intranasal and sublingual routes. METHODS: Ninety-three patients aged 0.5-10 yr were stratified by age: 30 infants and toddlers, 0.5-2 yr; 39 preschoolers, 2.1-5 yr; and 24 school age, 5.1-10 yr. They were randomized to receive 0.2 mg/kg of midazolam in the nose or under the tongue without or with additional flavoring. For the group receiving sublingual flavored midazolam, the syringe tip was dipped in candy flavor and sugar. Duration of crying and compliance with instructions for sublingual drug administration were recorded. Hemoglobin oxygen saturation by pulse oximetry and sedation score were recorded by three observers before drug administration, at 2.5-min intervals for 10 min, at separation from parents, and during induction with halothane in O2. RESULTS: Children accepted midazolam administered via the sublingual route better than that given intranasally. In children not crying before drug administration, the frequency and duration of crying was greater following intranasal compared with sublingual administration (71% vs. 18% (P < 0.0001) and 48 +/- 56 vs. 25 +/- 49 s (P = 0.004), respectively). Lack of total compliance with instructions for sublingual administration did not alter drug effect, and there were no differences between the three study groups in maximum sedation, response to separation from parents, and behavior at induction of anesthesia; 80% displayed adequate or excellent behavior. Finally, the addition of candy flavor did not improve acceptance of or compliance with sublingual midazolam administration. CONCLUSIONS: Sublingual administration of midazolam is as effective as, and better accepted than, intranasal midazolam as a preanesthetic sedative in children. PMID- 8489063 TI - Inhibitory effects of bupivacaine and lidocaine on adrenergic neuroeffector junctions in rat tail artery. AB - BACKGROUND: Various local anesthetic agents have been shown to cause relaxation of isolated vascular segments contracted by catecholamines and other constrictor drugs. This report describes the actions of the amide-linked local anesthetic, bupivacaine, on adrenergic responsiveness of isolated arterial smooth muscle, and compares bupivacaine effects with those of lidocaine. METHODS: Helical strips of rat tail artery mounted in a muscle bath for measurement of isometric force generation were contracted in response to adrenergic nerve stimulation, increased potassium concentration, tyramine, or exogenous norepinephrine. RESULTS: Treatment with bupivacaine or lidocaine caused depression of contraction to all four stimuli. Contraction to adrenergic nerve stimulation was more sensitive to the inhibitory effects of local anesthetics than was contraction to elevated potassium, tyramine, or exogenous norepinephrine. Furthermore, bupivacaine was more effective in reducing contraction to adrenergic nerve stimulation than was lidocaine (EC50: bupivacaine = 4 x 10(-6) M; lidocaine = 61 x 10(-6) M). In arteries incubated in solutions containing [3H]-norepinephrine and mounted for superfusion and isometric force recording, both bupivacaine and lidocaine (10(-5) M) depressed the contractions and diminished the release of radioactivity evoked by nerve stimulation. At the concentration tested, bupivacaine was more effective than lidocaine in reducing both contraction and the efflux of radioactivity as indicated by the magnitude of depression compared with control activities. CONCLUSIONS: These findings suggest that lidocaine and bupivacaine depress adrenergic neurotransmission and inhibit smooth muscle contraction. Bupivacaine is a more potent inhibitor of adrenergic neurotransmission in the blood vessel wall than is lidocaine. PMID- 8489064 TI - Anesthetic cutoff in cycloalkanemethanols. A test of current theories. AB - BACKGROUND: N-alkanols containing up to 12 carbons are anesthetic; however, those with more than 12 carbons are not. This phenomenon has been termed cutoff. Lipid disordering theories of anesthesia suggest that cutoff occurs because the alkyl chains of long-chain alcohols approach the length and shape of the lipids of neuronal membranes and, therefore, intercalate into membranes without perturbing them. Protein theories suggest that cutoff occurs because the size of long-chain alcohols exceeds that of a protein binding site having finite dimensions. These theories were tested with a new series of alcohols, the cycloalkanemethanols, c(CnH2n-1).CH2.OH. METHODS: Anesthetic potency was measured in Rana pipiens tadpoles using the reversible loss of righting reflexes as the endpoint. The change in order parameter induced by cycloalkanemethanols and n-alkanols in lipid bilayers made of egg phosphatidylcholine and cholesterol was measured with electron paramagnetic resonance spectroscopy. RESULTS: On ascending the series from cyclopropanemethanol (EC50 = 54 +/- 3.2 mM) to cycloundecanemethanol (EC50 = 7.0 +/- 0.12 microM) anesthetic potencies first increased exponentially but then decreased sharply at cyclododecanemethanol (EC50 = 13 +/- 0.2 microM). Cyclotetradecanemethanol was found not to cause anesthesia in tadpoles, even after 48 h of exposure, although saturated solutions shifted the dose-response curve of octanol from 66 +/- 2.6 to 47 +/- 2.8 microM. A linear loss in the ability to disorder lipid bilayers was observed on ascending both alcohol series such that cyclotetradecanemethanol and n-tridecanol actually increased bilayer order. CONCLUSIONS: Molecular length does not correlate with anesthetic cutoff in these two alcohol series. Cutoff is predicted by the ability of both series of alcohols to disorder lipid bilayers and correlates with their molecular volume. PMID- 8489065 TI - Inhibition by enflurane of baroreflex mediated mesenteric venoconstriction in the rabbit ileum. AB - BACKGROUND: Halothane and isoflurane are known to attenuate neurally mediated regulation of mesenteric vein diameter. The current study evaluated the effects of enflurane on baroreflex control of small mesenteric veins. METHODS: Changes in mesenteric vein diameter, intravenous pressure, mean arterial pressure, and heart rate in response to bilateral carotid occlusion, aortic nerve stimulation, and celiac ganglion stimulation were measured in 23 chloralose-anesthetized rabbits before, during, and after 1% and 2% inhaled enflurane administration. In six other rabbits, sympathetic efferent nerve activity was recorded directly from a postganglionic splanchnic nerve, also during bilateral carotid occlusion and aortic nerve stimulation, before, during, and after inhalation of 1% and 2% enflurane. RESULTS: Baseline mean arterial pressure and heart rate decreased, and mesenteric vein diameter increased, in response to inhaled enflurane. Reflex venoconstriction and the increases in mean arterial pressure, intravenous pressure, and heart rate, in response to bilateral carotid occlusion, were significantly inhibited at both levels of inhaled enflurane. Decreases in mean arterial pressure and heart rate, and reflex venodilation in response to aortic nerve stimulation, were attenuated by 2%, but not 1%, enflurane. Mesenteric venoconstriction, blood pressure increase, and bradycardia in response to celiac ganglion stimulation were unaffected by 2% inhaled and 5% superfused enflurane. Both 1% and 2% inhaled enflurane attenuated resting and carotid sinus-mediated increases in sympathetic efferent nerve activity. CONCLUSIONS: These results indicate that enflurane alters splanchnic venous reflexes in large part via the inhibition of sympathetic efferent activity. PMID- 8489066 TI - The influence of cryogenic brain injury on nociception in the rat. AB - BACKGROUND: Previous studies have suggested that focal cryogenic brain lesions that cause functional cerebral depression may increase anesthetic potency. To determine whether this effect was caused by changes in nociception, this study prospectively evaluated the influence of an experimental focal brain injury on the analgesic effects of the opioids, fentanyl and alfentanil, in rats. METHODS: The cortical freezing lesion was made with a brass probe cooled to -50 degrees C, applied through a craniotomy to the intact dura for 5 s. The analgesic effects of the opioids were quantified by tail-flick latency 3 days after the injury. The prolongation of tail-flick latency by infusions of each opioid in animals injured with a standardized cortical freezing lesion was compared with the results obtained from sham-operated control animals. RESULTS: At the endpoint of the experiment, prolongation of the tail-flick latency to 10 s, the mean serum concentrations (EC50) of both fentanyl and alfentanil were approximately 25% less in the brain-injured animals than in the controls (EC50 fentanyl; injured: 10.2 +/- 2.6 ng/ml, controls: 13.6 +/- 5.2 ng/ml [P < 0.02]; EC50 alfentanil; injured: 54.7 +/- 9.2 ng/ml, controls: 74.3 +/- 18.4 ng/ml [P < 0.02]). For alfentanil, no significant differences in pharmacokinetics between injured and control animals were observed. CONCLUSIONS: These results support the hypothesis that reductions in anesthetic requirements in this animal model of brain injury may be caused, in part, by alterations in nociception. PMID- 8489067 TI - The influence of intravascular volume expansion on cerebral blood flow and blood volume in normal rats. AB - BACKGROUND: Intravascular volume expansion can increase cerebral blood flow (CBF) in patients with cerebral ischemia. However, the changes in CBF produced by volume expansion in the normal brain remain the subject of debate, and the changes on cerebral blood volume (CBV; one determinant of intracranial pressure) have not been described. The effects of acute nondilutional volume expansion on cardiac output (CO), CBF, and CBV in normal rats were examined. METHODS: Normocarbic, normothermic halothane/N2O-anesthetized rats were given 0, 6, 12, 24, or 36 ml of a blood-hetastarch mixture (n = 6 for each group). When volume loading was completed, 3H-nicotine was used to measure CBF, while 99mTc-labeled red cells and 14C-dextran were used to measure cerebral red cell and plasma volumes. Animals were killed by microwave irradiation (8KW x 770 msec). In different animals, cardiac output (CO) was measured by thermodilution during the infusion of 36 ml of blood-hetastarch. RESULTS: Central venous pressure (CVP) increased from 3.9 +/- 0.7 mmHg (mean +/- SD) in control animals to 13.0 +/- 2.0 mmHg in rats given 36 ml of blood. Cardiac output increased to 138 +/- 11% of control. There were no changes in arterial Hct or mean arterial pressure. There were no significant changes in CBF (which varied from 127 +/- 22 ml.100 g-1.min-1 in controls to 102 +/- 14 after the infusion of 36 ml). However, CBV increased in a linear fashion with increasing CVP, from 2.96 +/- 0.57 ml/100 g in control conditions to 4.47 +/- 0.83 ml/100 g after the infusion of 36 ml of blood/hetastarch. CONCLUSIONS: In normal brain, CBF does not change during volume expansion, in spite of an increase in CO. This contradicts earlier studies, the results of which indicate an independent role for cardiac output in CBF control. Cerebral blood volume increased in proportion to CVP, suggesting simple passive venous distention. Whether this could increase ICP and compromise cerebral perfusion remains unclear. PMID- 8489068 TI - Effects of lidocaine on intracellular Ca2+ and tension in airway smooth muscle. AB - BACKGROUND: Many studies have demonstrated that lidocaine directly relaxes airway smooth muscle. The underlying mechanisms, especially in relation to Ca2+ mobilization, remain to be elucidated. METHODS: Using front-surface fluorometry and fura-2-loaded porcine tracheal smooth muscle strips, intracellular Ca2+ concentration ([Ca2+]i) and isometric tension were simultaneously measured. RESULTS: In cases of 40 mM K(+)-induced contraction and 1 microM acetylcholine (ACh)-induced contraction, the cumulative application of lidocaine (10(-6) approximately 3 x 10(-3) M) caused a concentration-dependent decrease in [Ca2+]i and tension, and almost complete relaxation. To examine the effect of lidocaine on Ca2+ sensitivity of the contractile apparatus, the [Ca2+]i-tension relationship was determined by changing the extracellular Ca2+ concentration during 40 mM K+ induced depolarization, with and without treatment with lidocaine. Although treatment with 1 mM lidocaine inhibited increases in both [Ca2+]i and tension induced by extracellular Ca2+, it had little effect on the [Ca2+]i-tension relationship. In the presence of 1 microM ACh, the [Ca2+]i tension relationship shifted markedly to the left, thereby indicating an increase in Ca2+ sensitivity of the contractile apparatus; this shift was inhibited by 1 mM lidocaine. In the absence of extracellular Ca2+, 1 mM lidocaine inhibited the release of stored Ca2+ induced by 1 microM ACh, but not that by 20 mM caffeine. CONCLUSIONS: Lidocaine directly relaxes airway smooth muscle by decreasing [Ca2+]i. In addition, lidocaine inhibits the ACh-induced increase of Ca2+ sensitivity of the contractile apparatus, although it has little effect on Ca2+ sensitivity during high K+ depolarization. The decrease in [Ca2+]i is attributed to inhibition of the influx of extracellular Ca2+, as induced by high K+ depolarization and by ACh, and to the inhibition of the ACh-induced release of stored Ca2+. PMID- 8489069 TI - Evaluation of a new fluid warmer effective at low to moderate flow rates. AB - BACKGROUND: The tendency of intravenous fluid exiting the heat exchanger of a fluid warmer to cool to room temperature increases as the rate of infusion slows and the length of tubing between the heat exchanger and the patient increases. Thus, slow to moderate flow rates result in the delivery of fluid near room temperature despite the use of a fluid warmer. The volumes infused even at low flow rates may be large relative to the size of infants and children and may result in a significant decrease in patient temperature. METHODS: A new warmer (Hotline, Level 1 Technologies) that actively heats the fluid in the delivery tubing was evaluated and compared to two different conventional dry-wall warmers: the model DW1000A (Baxter Health Care) and the FloTem IIe (DataChem). Cold blood (4-10 degrees C) and room temperature saline (22 degrees C) were pumped through the warmers and the delivered temperature was measured as the flow rate was varied from 50 to 12,000 ml/h. RESULTS: The Hotline was more effective than the Baxter or the FloTem IIe at flow rates between 50 and 6,000 ml/h for saline and at flow rates between 50 and 3,000 ml/h for blood. Insulating the tubing beyond the heat exchangers of the conventional warmers improved their performance, but the delivered temperatures were still less than those of the Hotline at low flow rates. CONCLUSIONS: The Hotline is more effective than conventional warmers at slow flow rates, and may be useful for preventing hypothermia when large volumes of fluid relative to patient size are infused at slow rates. PMID- 8489070 TI - Motor paralysis of the lower extremities following lumbar sympathetic block. PMID- 8489071 TI - Digitally assisted tracheal intubation in a neonate with Pierre Robin syndrome. PMID- 8489072 TI - Safe nasogastric tube placement in a patient with a basal skull fracture. PMID- 8489073 TI - Epidural versus intravenous fentanyl. PMID- 8489074 TI - Is nitroglycerin a myocardial depressant? PMID- 8489075 TI - Regional anesthesia for arteriovenous fistula. PMID- 8489076 TI - Laryngeal mask airway and difficult intubation. PMID- 8489077 TI - Left bronchial intubation by the laryngectomy tube. PMID- 8489078 TI - Heart block after methylmethacrylate cementing. PMID- 8489079 TI - Electrocardiographic changes during cesarean section. PMID- 8489080 TI - The relationship between timing of repair of disruptions and subsequent aneurysm formation in laser-assisted microvascular anastomoses. AB - In this study we investigated the effects of duration of bleeding after laser assisted microvascular anastomoses and the amount of laser energy used to control bleeding on aneurysm formation. Eighty femoral arteries were exposed in 40 Sprague-Dawley rats anesthetized with chloral hydrate. The arteries were transected and then anastomosed end-to-end with three nylon stay sutures followed by irradiation of the vessels with energy from a CO2 laser. The laser power was kept at 90 mW, and each of three segments between stay sutures was exposed for 6 seconds to continuous laser energy. If anastomotic disruption (defined as bleeding after completion of the anastomosis) occurred, it was controlled with pressure over the disrupted site for 10, 25, or 40 seconds. Disruptions were required with exposure to additional laser energy for either 6 (group 1) or 12 seconds (group 2). The anastomoses were inspected at 21 days postoperatively to assess patency and aneurysm formation. Twenty-six of 80 vessels (32%) were anastomosed without the occurrence of disruptions: these 26 vessels had a 100 per cent patency rate and did not develop aneurysms. In group 1, the incidence of redisruption following a primary disruption was the same irrespective of duration of bleeding (4/8, 3/6, and 3/6 for 10-, 25-, and 40-seconds bleeding time, respectively P = NS). Similarly, there was no difference in the incidence of aneurysm formation in this group (0/8, 2/6, and 2/6 for 10, 25, and 40", respectively, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489081 TI - Prevention of seroma formation after dissection of musculocutaneous flaps. AB - Dissection of musculocutaneous flaps is uniformly followed by the formation of seroma if drains are not used. Drains can be colonized and form deep tissue infection if left in place for a long time. In this study we investigated whether talc poudrage could prevent the formation of seroma following dissection of the latissimus dorsi muscle in a canine model. Twelve mongrel dogs were randomized into two groups. Group 1 (n = 6) underwent dissection of the left latissimus dorsi muscle which was rotated as a pedicle flap into the left chest through a second intercostal space thoracotomy. The wound was closed in layers without drains. Group 2 (n = 6) had the same procedure, but before closure of the wound, USP talc was applied to the tissues. All animals received cefazolin (500 mg) Q8h for 48 hours perioperatively. Animals were followed for 1-5 months. Wounds with fluctuation were aspirated as many times as necessary and the amount of fluid was recorded. All Group 1 animals developed seromas, in contrast, only one animal in group 2 had a seroma. There was a significant difference in the amount of fluid aspirated for each animal between the two groups (280 +/- 80 in group 1 vs 25 +/- 25 ml in group 2, P < 0.05). The total amount of fluid drained in group 1 was 1730 ml, whereas only 150 ml was aspirated in group 2. Group 1 animals required a total of 11 aspirations to control seromas, in contrast, only one aspiration was needed in group 2. No abscess was identified at postmortem in either group. Based on the results of this study we conclude that talc poudrage can be safely used to minimize seroma formation after dissection of musculocutaneous flaps. PMID- 8489082 TI - Pyogenic hepatic abscess: a case for open drainage. AB - A retrospective review of 24 patients treated at the University of Chicago for pyogenic liver abscess from 1979 to 1989 was performed to determine if there is a changing etiology in pyogenic liver abscess and if percutaneous drainage is a reliable treatment alternative to open drainage. Biliary tract disease was the most common cause and presented in 29 per cent of patients. Klebsiella and enterococcus were the most common bacterial organisms cultured in 33 and 29 per cent of patients, respectively. The overall mortality rate was 25 per cent, however, if open drainage, in addition to a definitive procedure such as cholecystectomy or bowel resection was performed, there were no deaths. We therefore recommend the use of percutaneous drainage alone only in selected patients. PMID- 8489083 TI - Atypical thyroglossal duct cyst: a rare cause for a solitary cold thyroid nodule in childhood. AB - A case of an atypical thyroglossal duct cyst is described in a 9-year-old boy who presented with a lateral neck mass that was hypofunctioning on thyroid scan and clinically indistinguishable from a thyroid nodule. Preoperative fine needle aspiration biopsy results demonstrating abundant, normal appearing squamous epithelial cells and keratinaceous material was suggestive of the diagnosis. Definitive diagnosis was made only after complete mobilization of the left lobe of the thyroid gland and cyst resection. A standard Sistrunk procedure was performed, and cyst excision was accomplished without resection of the left lobe of the thyroid gland. Microscopic examination disclosed a keratinizing pseudostratified squamous epithelium that has not been previously reported with thyroglossal duct cysts. PMID- 8489084 TI - Asymptomatic and normocalcemic parathyroid adenoma: detection by preoperative ultrasound. AB - Hyperparathyroidism is often detected in the asymptomatic stage at the present time with the advent of mass screening for hypercalcemia. There may be patients with parathyroid disease who are asymptomatic and who do not have detectable elevations of their serum calcium. Many patients who undergo surgery for thyroid conditions may have synchronous parathyroid disease which is asymptomatic and not detectable by routine laboratory screening. Preoperative ultrasound scans may be of utility in identifying coexistent disease in those patients scheduled for thyroid surgery so that both disease entities may be treated at the same operation. PMID- 8489085 TI - Laparoscopically guided cholecystectomy: a detailed report of the first 453 cases performed by one surgical team. AB - This study reports outcome data from a diverse population undergoing laparoscopic cholecystectomy. Our technique differs from other laparoscopic methods in its use of electrocautery, blunt hilar dissection, and routine intraoperative cholangiography. This study includes 453 consecutive surgeries performed between August 1989 and March 1991. Only the first 20 patients were screened to exclude those with common bile duct stones, prior upper abdominal surgery, pregnancy, or acute cholecystitis. Patients had the following conditions: current acute cholecystitis (9%), a history of acute cholecystitis (16%), jaundice (5%), pancreatitis (4%), and prior abdominal surgery (38%). Nine per cent had common bile duct stones which were treated with either laparoscopic transcystic common bile duct exploration (69%), laparoscopic choledochotomy (5%), open choledochotomy (10%), endoscopic retrograde cholangiopancreatography (10%), or observation (7%). Operative time averaged 78 minutes. One patient died, and 6% developed complications. Seventy-one per cent were discharged on the first postoperative day. Our experience demonstrates that LC can be performed safely, even in difficult cases, although considerable endoscopic experience and skill are required. PMID- 8489086 TI - Biliary complications of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has rapidly become the preferred treatment for symptomatic gallstones. Although this procedure has certain advantages over open cholecystectomy, concern has been expressed regarding the potential for bile duct injuries. In an effort to understand the scope of this problem, a retrospective review was performed of all patients referred to UCLA after having sustained biliary injuries during laparoscopic cholecystectomy. Over a 14-month period, 10 patients were referred to UCLA with 12 major bile duct injuries. One patient had a false positive cholangiogram leading to an unnecessary biliary-enteric bypass and subsequent dehiscence, resulting in a biliary fistula. Six patients were referred on an acute basis, whereas four patients underwent attempted biliary reconstruction at outside facilities and were ultimately referred with either a biliary stricture or a fistula. Review of cholangiograms suggested that bile duct anomalies were present in five patients. There did not appear to be a relationship between the use of either electrocautery or laser and bile duct injuries. To date eight patients have been successfully managed via Roux-en-Y hepaticojejunostomies, with a mortality rate of 0%. Although the exact frequency cannot be ascertained from the current study, our data demonstrate that major biliary complications do occur during laparoscopic cholecystectomy. Most of these injuries, however, can be safely and successfully treated with surgical biliary reconstruction. Early diagnosis and treatment with liberal use of intraoperative cholangiography and a low threshold for conversion to open laparotomy appears to be associated with a more favorable outcome. PMID- 8489087 TI - Prospective randomized study of two different doses of clindamycin admixed with gentamicin in the management of perforated appendicitis. AB - Septic complications after surgery for enterogenous peritonitis are minimized by adjuvant antibiotics effective against aerobes and anaerobes. Historically, "gold standard" therapy included an aminoglycoside plus clindamycin, the latter given at 600 mg intravenous piggyback (IVPB), every 6 hours. Clindamycin pharmacokinetics suggests that it can be given q8h and admixed with gentamicin, thereby markedly reducing the cost of administration. Although this is now common practice, there is no prospective study comparing the efficacy of the two dose schedules in peritonitis. This study was designed to test the hypothesis regarding the clinical efficacy of the two regimens. One hundred twenty-six patients with gangrenous (n = 34) or perforated appendicitis (n = 91) were randomized (2:1) to receive gentamicin admixed with clindamycin 900 mg IVPB every 8 hours (Group I n = 80) or gentamicin IVPB q8h plus clindamycin 600 mg IVPB every 6 hours (Group II n = 46). Appendectomy was performed, and aerobic and anaerobic cultures were obtained. Twenty-one patients had simultaneous determinations of clindamycin levels in plasma, peritoneal fluid, and appendix. Outcome analysis revealed no significant differences in postoperative days of fever, days non per os, antibiotic therapy, or hospitalization. There were 6 failures (4 abscesses and 2 wound infections) in Group I and 4 failures (1 abscess and 3 wound infections) in Group II. Both antibiotic regimens provided clinically equivalent results in mixed infections due to aerobic and anaerobic bacteria. The admixed clindamycin, administered every 8 hours, results in at least 20% reduction in costs. This is an important consideration. PMID- 8489088 TI - The enigma of leiomyoblastoma: spectrum of a rare gastric tumor. AB - Leiomyoblastoma is a rare, smooth muscle tumor of the stomach occurring chiefly in the antrum in patients between the fifth and seventh decades. The clinical spectrum, as illustrated in eight patients described in this report, ranges from an incidental finding to a highly malignant, metastasizing neoplasm. Although the large majority of leiomyoblastomas are benign, malignancy has been reported to occur in up to 12% of cases. Resection of the tumor with an appropriate full thickness segment of gastric wall is mandatory. PMID- 8489089 TI - Impact of anesthetic agents on patients with sickle cell disease. AB - Fifty-two surgical procedures were performed on 45 patients with sickle cell anemia. All patients were managed perioperatively with hydration and were kept warm and well oxygenated. Patients were anesthetized with either halothane (n = 16), enflurane (n = 22), isoflurane (n = 6), or intravenous narcotics (n = 4). Four patients had epidural anesthesia. Perioperative morbidity was assessed using the criteria of atelectasis, urinary tract infection, wound infection, thrombophlebitis, drug reaction, hypotension, and vaso-occlusive crisis. The overall perioperative complication rate in this study was 45 per cent. Patients anesthetized with isoflurane and enflurane had postoperative morbidity rates of 83 and 59 per cent, respectively, while the patients anesthetized with halothane had a complication rate of 25 per cent. In all three groups, atelectasis was the main cause. No complications occurred in the epidural group. In the intravenous anesthesia group, one patient developed sickle cell crisis. It appears that the types of anesthetic agents used do not impact on postoperative morbidity in patients with sickle cell anemia more than any other type of patient. PMID- 8489090 TI - Anterior resection for the treatment of rectal prolapse: a 20-year experience. AB - Between 1971 and 1991, 41 patients underwent anterior resection for the treatment of complete rectal prolapse. Anterior resection was performed after full rectal mobilization to the levator ani muscles with reanastomosis (39 hand-sewn and two stapled) carried out to peritonealized distal rectum. The 41 patients comprised 35 women and six men with an average age of 56 years (range, 7-88 years). Postoperative follow-up averaged 6 years (range, 6 months to 18 years). Three patients (7%) suffered recurrent prolapse in 2, 2.5, and 5.5 years, respectively. Mortality was 0 per cent; morbidity was 15 per cent including three incisional herniae, two small bowel obstructions, and one stroke. No pelvic sepsis, abscess, or anastomotic dehiscence occurred. Anal incontinence was a preoperative finding in 21 patients (51%) with rectal prolapse. Nineteen of these patients (90%) noted either improvement or no change in postoperative continence. Anterior resection is a familiar, frequently performed operation that does not require a foreign body or rectal suspension. We believe this to be the procedure of choice for patients with complete rectal prolapse. Anterior resection withstands long-term scrutiny both in terms of recurrence rate and associated complications. PMID- 8489091 TI - Endoscopic resection of primary rectal teratoma. AB - A 76-year-old female was noted to have a rectal mass on evaluation for postmenopausal bleeding. There was no history of abdominal pain, constipation, or rectal bleeding. Flexible sigmoidoscopy revealed a 3-cm pedunculated rectal mass at 10 cm. Hair fibers were visible through the smooth glistening surface. At colonoscopy, the polyp was removed by snare polypectomy. Histology showed epidermal, mesodermal, and endodermal components diagnostic of benign cystic teratoma. Subsequent total abdominal hysterectomy and bilateral salpingo oophorectomy revealed endometrial carcinoma and postmenopausal ovaries. Primary rectal teratoma is a very rare rectal mass that may present endoscopically. Since 1865, only 33 cases have been reported in the literature. Endoscopic photographs, histology, and a review of the literature are presented. PMID- 8489092 TI - Kinevac-assisted cholescintigraphy as an accurate predictor of chronic acalculus gallbladder disease and the likelihood of symptom relief with cholecystectomy. AB - Thirty patients with chronic upper abdominal pain and no evidence of cholelithiasis were entered into this study. All had negative ultrasonography of the gallbladder, and most had a host of other negative investigations. These patients were referred to a surgeon to evaluate the possibility of atypical biliary colic associated with chronic acalculous cholecystitis. All patients underwent cholecystokinin-stimulated cholescintigraphy and were offered cholecystectomy if the ejection fraction was less than 35 per cent. Of the 30 patients, 27 (90%) had pathologically abnormal gallbladders. Follow-up averaged over 1 year (13.2 mo), and relief of symptoms occurred in 28 (94%). The authors conclude that in appropriately selected patients with symptoms of biliary colic (typical or atypical) and no evidence of cholelithiasis, a cholecystokinin stimulated cholescintigram is a significant help in predicting not only which patients have gallbladder disease, but also how likely cholecystectomy is to result in an improvement in their symptoms. PMID- 8489093 TI - Anatomic variance in the cholecystic blood supply: a case report. AB - The cystic artery is known to arise from many possible origins; with the right hepatic artery is the most common. Other origins of the cystic artery include the left hepatic artery, the common hepatic artery, and the superior mesenteric artery. In addition to the variability in origin of the cystic artery, its course can also follow diverse paths, often in close proximity to the common bile duct. This report presents a rare and, to our knowledge, previously unreported deviation of the cystic artery's origin and course that was encountered during cholecystectomy. This rare variant emphasizes the importance of a thorough knowledge of cystic arterial variations that often occur and may be encountered during both open and laparoscopic cholecystectomy. PMID- 8489094 TI - Pharmacologic hemostasis in laparoscopy: topical epinephrine facilitates cholecystectomy. AB - Bleeding may become a major impediment to accurate and safe dissection by laparoscopy. The traditional maneuvers of pressure, dumping, irrigation, and aspiration frequently applied during open procedures to maintain a clear field of dissection are cumbersome through laparoscopy. Several pharmacologic agents have been used topically or by local injection to stop bleeding or to prevent excessive blood loss during surgical procedures. They include calcium alginate, aluminum salts, silver nitrate, formalin, and coagulating agents like thrombin and collagens, all of which leave a layer of damaged tissue or foreign material on the surface. Epinephrine and vasopressin have been employed mostly by local injections. We report the use of topical epinephrine applied before and during the dissection of the cystic duct and artery area in the course of laparoscopic cholecystectomy. A 3/8-inch gauze sponge, impregnated with a 1:10,000 epinephrine solution, was used to blanch the tissues and to bluntly dissect the cystic duct and artery. It was also used to control minor bleeding in the gallbladder fossa. The prophylactic bleeding control with topical epinephrine proved to be an easy and safe maneuver, and greatly facilitated the dissection of the most critical areas during laparoscopic cholecystectomy. This technique may be applicable to laparoscopic dissection for other procedures. PMID- 8489095 TI - The role of endoscopic retrograde cholangio-pancreaticrogram in laparoscopic cholecystectomy. AB - Four hundred and fifty-nine patients were studied to evaluate the role of diagnostic and therapeutic endoscopic retrograde cholangio-pancreaticrogram (ERCP) in their management before laparoscopic cholecystectomy (LC) when choledocholithiasis is suspected. Using bilirubin, liver function tests (LFTs) (alkaline phosphatase, SGOT, SGPT) and findings on ultrasound of a dilated common bile duct (CBD), 37 patients (8.1%) were suspected of having concomitant common bile duct stones preoperatively. These patients were subjected to the following diagnostic and therapeutic procedures: 25 ERCPs, 20 laparoscopic cholangiograms, and three extracorporeal shock wave lithotripsies. Preoperative ERCP was done on 19 patients, intraoperative ERCP-sphincterotomy was done on one patient, and postoperative ERCP-sphincterotomy was done on five patients. Fifteen laparoscopic cholangiograms were done as primary tests and five after preoperative ERCP. Sixteen patients (3.5%) had stones in their CBD. Four patients had their laparoscopic cholecystectomy cancelled, and one patient had laparoscopic common duct exploration that was converted to an open procedure. Three groups were identified: group I, patients with a high index of suspicion, included elevated bilirubin with elevation of all three LFTs, or normal bilirubin with elevation of all three LFTs with or without dilated CBD. Seventy-five per cent of this group had CBD stones. Group II, patients with a low index of suspicion, included normal bilirubin and normal CBD by ultrasound with elevation of the alkaline phosphatase alone or elevation of two of the three LFTs. Six per cent of this group had CBD stones. Group III, patients with no index of suspicion, were patients with normal preoperative laboratory test results and CBD. Two patients (0.47%) in this group had elevated LFTs postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489096 TI - Two pitfalls of laparoscopic balloon cholangiography: recognition and correction. AB - The balloon cholangiocater has become popular for laparoscopic intraoperative cholangiography. Two pitfalls of this instrument include apparent common bile duct injury and pseudo-Mirizzi anatomy. These pitfalls are illustrated, and their correction is discussed. PMID- 8489097 TI - Gastric schwannoma. Clinical and pathologic considerations. AB - Solitary gastric schwannomas are rare clinical entities. Presented are three cases encountered in a single hospital in a 4.5-year period. Solitary gastric schwannomas represent a small percentage of schwannomas and a small percentage of gastric tumors. These tumors are usually asymptomatic and may present as upper gastrointestinal bleeding or as mass lesions. Upper endoscopy is important in the initial evaluation of these patients. Pathologic diagnosis is based on features of palisading nuclei, spindle-cell morphology, and hyalinized vessels. Immunohistochemical stains and electron microscopy may be helpful for diagnosis. Complete excision of the tumor is adequate treatment. The risks of coexistent malignancies have not been stressed, but this association may be important; therefore, we recommend a diligent search for other tumors. Prognosis following treatment is good. PMID- 8489098 TI - Irrigation of the abdominal cavity in the treatment of experimentally induced microbial peritonitis: efficacy of ozonated saline. AB - Ozone is an oxidizing agent possessing potent in vitro microbicidal capacity. This study was designed to address the extent to which irrigation of the contaminated abdominal cavity using a saline solution primed with ozone is effective in reducing morbidity and mortality. Gelatin capsules containing different quantities of a premixed slurry of filtered human fecal material were implanted in the peritoneal cavities of a preliminary series of rats. Three inocula concentrations were selected for later experiments, based upon their ability to produce morbid consequences: (1) high (100% 1-day mortality), (2) medium (70% 3-day mortality, 100% abscess rate in survivors), and (3) low (100% 10-day survival, 100% abscess rate). Fecal and abscess bacteriology were similar in all rats. The peritoneal cavities of 240 rats then underwent fecal-capsule implantation (three groups of 80 rats/inoculum concentration). At celiotomy 4 hours later, equal numbers of rats from each group were randomly assigned to one of four protocols: (1) no irrigation, (2) normal saline irrigation, (3) saline cephalothin irrigation, and (4) ozonated saline irrigation. Each treatment lasted 5 minutes, using 100 ml of irrigation fluid. Mortality was significantly reduced when, in lieu of no irrigation, any of the irrigation solutions were used. Additionally, ozonated saline statistically proved the most effective irrigating solution for reducing abscess formation in survivors. PMID- 8489099 TI - Implications of risk factors in necrotizing fasciitis. AB - The following risk factors, previously associated with necrotizing fasciitis, were identified in 25 consecutive patients: diabetes mellitus, intravenous drug abuse, age greater than 50, hypertension, and malnutrition/obesity. Additional data recorded included the duration of illness to the time of the first operative procedure, the type of procedure performed, the anatomic location of the infection, the etiology, culture reports, and leukocyte counts. The goal of this study was to determine whether the number of risk factors present in a patient was predictive of mortality. Six patients (24%) died and 19 patients survived. The nonsurvivors exhibited a significantly higher percentage of diabetes mellitus, 83 per cent versus 37 per cent (P = 0.047). Fifteen of 19 survivors (79%) and only one of six nonsurvivors (17%) had fewer than three risk factors (P = 0.006). In conclusion, more than three previously identified risk factors present in patients with necrotizing fasciitis were found to be predictive of a mortality rate of 50 per cent. The mainstay of treatment remains aggressive surgical intervention, broad-spectrum antibiotics, and nutrition support. PMID- 8489100 TI - A critical analysis of adjuvant techniques used to assess bowel viability in acute mesenteric ischemia. AB - Delayed revascularization and inaccurate assessment of bowel viability in acute mesenteric ischemia can be catastrophic. We reviewed the outcome of three popular adjuvant techniques used to evaluate bowel viability in all 16 patients who had second-look abdominal explorations following revascularization for acute mesenteric ischemia from 1984 to 1989. Each adjuvant technique was reviewed separately and compared with the unequivocal end points of viable or nonviable bowel. The sensitivity (percentage of nonviable bowel correctly identified), specificity (percentage of viable bowel identified), predictive value (percentage of bowel identified as "nonviable" that proved to be so), and overall accuracy (percentage of correct evaluations) were determined for each method. The overall accuracy of clinical judgment, fluorescein fluorescence, and Doppler was 50 per cent, 56 per cent, and 0 per cent, respectively. Based on this critical review, we recommend routine second-look explorations in patients with acute mesenteric ischemia to reassess bowel that has been predicted to be viable or to resect bowel that has progressed to infarction. PMID- 8489101 TI - Risk of complication in perforated duodenal ulcer operations according to the surgical technique employed. AB - We prospectively analyzed a homogeneous group of 65 patients with perforated duodenal ulcer whose medical condition (no perioperative shock, no associated disease, underwent laparotomy within 12 hours after perforation, and an APACHE II score below 11) would have little effect on the outcome of surgery to study the influence of the surgical procedure (suture closure, vagotomy, or gastrectomy) on the morbidity and mortality rate. Thirty-three patients (51%) underwent vagotomy, 25 (38%) simple suture closure, and seven (11%) gastrectomy. Five patients (8%) suffered postoperative complications, two (3%) required further operation, and one (1.5%) died of pulmonary sepsis. Statistical analyses revealed that "vagotomy" presented significantly better results than did "simple suture" and "gastrectomy" that had similar results. The type of surgery, however, was not a significant risk factor in predicting complications in this sample. This study points out the need to stratify the perforated duodenal ulcer patients for accurate investigations. It also shows that definitive operations (gastrectomy or vagotomy) do not increase surgical risk in this group of patients, and, considering the poorer results with simple suture closure compared to vagotomy, the latter is an attractive option because it also treats the underlying ulcer disease. PMID- 8489102 TI - Delayed presentation of an inflammatory polyp following colonic ischemia. AB - Inflammatory polyps are usually associated with inflammatory bowel disease. The majority of these lesions are asymptomatic, however, they may be a source of obstruction or hemorrhage. These polyps represent re-epithelialization of the damaged colonic mucosa. Although inflammatory polyps have been associated with the acute phase of ischemic colitis, there has been only one report of delayed presentation of a symptomatic inflammatory polyp following ischemic injury to the colon. We present the second such report and a review of the literature. PMID- 8489103 TI - Perforated gastric and duodenal ulcer: an analysis of prognostic factors. AB - A review of patients treated operatively for perforated ulcer was undertaken to determine factors that independently predict mortality and morbidity. From 1980 to 1989 84 patients were treated with operative mortality and morbidity rates of 18 and 37 per cent, respectively. Patients with gastric ulcer were significantly older and were more likely to have concomitant medical problems, to use steroids, and be hospitalized at time of their perforation. They also had a higher perioperative mortality rate when compared to patients with gastroduodenal ulcers (P < 0.05 for each). Patients treated with definitive operation (n = 51) had a significantly lower recurrent ulcer rate when compared to an equivalent group treated with simple closure (n = 33) (mean follow-up, 47 months). Multivariate analysis confirmed a patient's likelihood of complication or death could be predicted using three variables (P < 0.03); age greater than 42 years, hospitalization at time of perforation, concomitant medical illness. While the relative distribution of these three factors in patients with gastric versus peptic ulcers appears to account for the difference in outcome between these two groups, the distribution of these factors between patients treated with patch closure and definitive operation was not significantly different. Patient outcome from operation for perforated ulcer is dependent on preoperative conditions and appears to be independent of surgical procedure performed. There was no benefit to simple closure of a perforated ulcer. Definitive procedures of perforated ulcers are associated with lower ulcer recurrence and therefore are advocated to treat perforation. PMID- 8489104 TI - Laparoscopic reduction of acute gastric volvulus. AB - The traditional surgical treatment of gastric volvulus involves upper abdominal laparotomy with gastric detorsion, fixation, and, when present, repair of associated diaphragmatic hernia. We describe a case of organoaxial gastric volvulus associated with a paraesophageal hernia in a poor risk patient, which was successfully treated with laparoscopic detorsion and percutaneous endoscopic gastropexy. This approach avoided the morbidity of a laparotomy and allowed the rapid recovery of gastric function. PMID- 8489105 TI - Abusive scald burns in infants and children: a prospective study. AB - Between July 1, 1987 and June 30, 1990, 30 consecutive deliberately scalded children were studied prospectively. Purposes of the study were to characterize the scald-abused child and address the management problems specific to this group. Mean age was 22.5 months. Many had preburn growth retardation. Mean burn size was 18.1 per cent of the total body surface area and 37 per cent required a surgical procedure for their scald. All 30 children had burns on the buttocks. Four (13.3%) had other injuries. Eighty per cent of patients had at least one complication. In 30 per cent, diarrhea complicated nutrition support, wound, or autograft care. Four (13.3%) patients with a mean burn size of 32.3 per cent of the total body surface area, diarrhea, and burns involving the buttocks, perineum, and external genitalia died of burn wound sepsis; three of these had Gram-positive bacteremia (Staphylococcus aureus and enterococcus). Burn wounds exposed to the fecal stream (buttocks) should be examined carefully and frequently for signs of infection, particularly in those patients with diarrhea. PMID- 8489106 TI - A clinical and immunologic evaluation of women with silicone breast implants and symptoms of rheumatic disease. AB - OBJECTIVE: To describe the clinical and serologic features of women with silicone breast implants who were referred for symptoms of rheumatic disease. DESIGN: A case series. SETTING: University and private rheumatology practices. PATIENTS: A total of 156 women with silicone breast implants and rheumatic disease complaints. Controls for the serologic studies included women with silicone implants and no rheumatic symptoms (n = 12) and women with fibromyalgia without silicone implants (n = 174). MEASUREMENTS: Complete physical examination and testing for immunoglobulins; complement; C-reactive protein; rheumatoid factor; and autoantibodies by indirect immunofluorescence, immunodiffusion, and Western blot. RESULTS: Three subgroups of patients were defined based on clinical and laboratory findings: joint and muscle pain (n = 95), joint swelling (n = 32), and connective tissue disease (n = 29). Most women had normal immunologic studies. The patients with joint swelling had mild, asymmetric, rheumatoid-factor-negative synovitis that did not meet American College of Rheumatology criteria for rheumatoid arthritis. Fourteen patients had a scleroderma-like illness and anti centromere or anti-PM-Sci antibodies by Western blot. Ten patients had a positive Western blot for BB' polypeptide, a small nuclear ribonucleoprotein (snRNP), but did not meet criteria for systemic lupus erythematosus. No autoantibodies to known disease-related polypeptides were detected on Western blot in the control groups. CONCLUSION: Most women with silicone implants and rheumatic complaints had normal results of serologic tests and nonspecific symptoms, suggesting no serious connective tissue disease. However, a subset of women had clinical signs and serologic tests that were unusual even for referred patients. These observations suggest, but cannot establish, that some women with silicone breast implants may develop atypical immunologic reactions. PMID- 8489107 TI - High-dose weekly intravenous immunoglobulin to prevent infections in patients undergoing autologous bone marrow transplantation or severe myelosuppressive therapy. A study of the American Bone Marrow Transplant Group. AB - OBJECTIVE: To determine whether intravenous immunoglobulin (IVIG) prevents severe infections during autologous bone marrow transplantation or equivalent high-dose myelosuppressive therapy. DESIGN: Randomized, stratified, nonblinded study. SETTING: Three tertiary care university hospitals. PATIENTS: One hundred seventy patients entered the study; 82 received IVIG and 88 were untreated controls. The study groups were similar for parameters capable of influencing the likelihood of infection. INTERVENTIONS: Intravenous immunoglobulin was given weekly at a dose of 500 mg/kg body weight from the initiation of cytotoxic therapy to the resolution of neutropenia. MEASUREMENTS: The development of bloodstream or other clinically proven infection, platelet use, and the development of alloimmunity to platelet transfusion. RESULTS: Clinical infection, bacteremia, and fungemia occurred in 43%, 35%, and 6% of the IVIG-treated patients and in 44%, 34%, and 9% of the control patients. Gram-positive bacteremia and gram-negative bacteremia occurred in 28% and 11% of the IVIG group and in 23% and 13% of the control group. Death due to infection occurred in 4.9% of IVIG recipients and in 2.3% of controls. None of these observations was statistically significant (P > 0.2). Survival to hospital discharge was achieved in 86.6% of the IVIG group and in 96.6% of the control group. The survival difference (10%; 95% CI, 1.7% to 18.3%; P = 0.02) was due to a higher incidence of regimen-related toxic death in the IVIG-treated group. CONCLUSIONS: The use of IVIG did not prevent infection. Fewer deaths occurred among controls due to a higher incidence of fatal hepatic veno occlusive disease in patients receiving IVIG. PMID- 8489108 TI - Vagal cardiovascular reflexes in young persons with syncope. AB - OBJECTIVE: To study the neurocardiologic reflexes in young persons who have fainted under conditions of emotional stress. DESIGN: Case-control study. SETTING: Clinical neurophysiology laboratory in Haifa, Israel. PATIENTS: Sixty persons (41 women and 19 men), 15 to 17 years old, who were referred for study because of syncope related to an emotionally distressing event. Forty aged matched, healthy volunteers drawn from the same population served as controls. MEASUREMENTS: Resting electrocardiogram, inspiratory-expiratory difference in heart rate during deep breathing, heart rate response to the Valsalva maneuver, and blood pressure during motionless standing for 5 minutes. RESULTS: Although individual results were within widely accepted limits of normal, patients with syncope as a group had higher vagal autonomic tone than did controls. This manifested as a slower heart rate at rest (mean, 67.8 beats/min compared with 73.2 beats/min; P = 0.005), a higher inspiratory-expiratory difference in heart rate (mean, 44.1 beats/min compared with 37.9 beats/min; P = 0.001), and a higher Valsalva ratio (1.91 compared with 1.72; P < 0.0001). No significant difference was found in the PR and QTc (QT interval corrected for rate) intervals of the electrocardiogram or in the blood pressure response to standing. CONCLUSION: Many young persons who faint under conditions of emotional distress do so because a relatively high vagal tone predisposes them to the cardioinhibitory component of the syncope. Age-related physiologic reduction in vagal cardiac responses may explain the lower incidence of this type of syncope with increasing age. PMID- 8489109 TI - Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barre syndrome. AB - OBJECTIVE: To determine if patients with the Guillain-Barre syndrome are likely to have had Campylobacter jejuni infection before onset of neurologic symptoms. DESIGN: A case-control study. SETTING: Several university medical centers. PATIENTS: Case patients met clinical criteria for the Guillain-Barre syndrome between 1983 and 1990 and had a serum sample collected and frozen within 3 weeks after onset of neurologic symptoms (n = 118). Disease controls were patients with other neurologic illnesses (n = 56); healthy controls were hospital employees or healthy family members of patients (n = 47). MEASUREMENTS: Serum IgA, IgG, and IgM antibodies to C. jejuni were determined by enzyme-linked immunosorbent assays. Assays were done in a blinded manner. RESULTS: Optical density ratios > or = 2 in two or more immunoglobulin classes were seen in 43 (36%) of patients with the Guillain-Barre syndrome and in 10 (10%) of controls (odds ratio, 5.3; 95% CI, 2.4 to 12.5; P < 0.001). Increasing the optical density ratio or the number of immunoglobulin classes necessary to yield a positive result increased the strength of the association. The number of patients with the Guillain-Barre syndrome who had positive serologic responses was greatest from September to November (P = 0.02). Male patients were three times more likely to have serologic evidence of C. jejuni infection (P = 0.009); the proportion of patients with the syndrome who had a positive serologic response increased with age. CONCLUSIONS: Patients with the Guillain-Barre syndrome are more likely than controls to have serologic evidence of C. jejuni infection in the weeks before onset of neurologic symptoms. Campylobacter jejuni may play a role in the initiation of the Guillain Barre syndrome in many patients. PMID- 8489110 TI - Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. AB - PURPOSE: To evaluate the possibility that fibrinogen represents a cardiovascular risk factor. DATA IDENTIFICATION: A computerized literature search (1980 to 1992) identified all published epidemiologic studies on fibrinogen and cardiovascular disease. Clinical and basic research data were found by separate searches. References of all papers thus obtained were studied and relevant papers included. STUDY SELECTION: Six prospective epidemiologic studies were included in a meta analysis (one study was excluded because the study population was non representative). Clinical papers were reviewed separately for other evidence of causation. DATA EXTRACTION: The correlation of fibrinogen levels on the subsequent incidence of myocardial infarction, stroke, and peripheral arterial occlusive disease was assessed and the causality of the association was analyzed. Calculations were made to examine fibrinogen level (in tertiles) versus cardiovascular risk. Odds ratios of high versus low tertile were computed. RESULTS OF DATA ANALYSIS: All prospective studies showed that fibrinogen was associated with subsequent myocardial infarction or stroke. A total of 92,147 person-years was covered by these investigations. Odds ratios varied between 1.8 (95% CI, 1.2 to 2.5) in the Framingham and 4.1 (CI, 2.3 to 6.9) in the GRIPS study, with a summary odds ratio of 2.3 (CI, 1.9 to 2.8). Associations existed between fibrinogen and other cardiovascular risk factors, but after multivariate analysis, only the association between fibrinogen and cardiovascular events remained. The majority of the preconditions for causality were fulfilled, indicating that fibrinogen is pathophysiologically related to cardiovascular events. CONCLUSIONS: Fibrinogen can be considered a major cardiovascular risk factor. Future studies of cardiovascular morbidity and death should include this variable. PMID- 8489111 TI - Cognitive behavioral techniques for hypertension: are they effective? AB - PURPOSE: To assess by analysis of published controlled trials the efficacy of cognitive behavioral therapies (such as biofeedback, relaxation, meditation) for essential hypertension. DATA IDENTIFICATION: Randomized controlled trials published in the English language between 1970 and 1991 identified from the MEDLINE database and bibliographic references from these articles. STUDY SELECTION: Limited to studies involving randomized assignment to a treatment group consisting of one or more cognitive behavioral interventions or a concurrent control group consisting of no therapy, a waiting list, regular monitoring, or placebo intervention. RESULTS OF DATA SYNTHESIS: Although we identified more than 800 published works, only 26 met entry criteria. We identified a number of methodologic short-comings, including small sample size, inconsistencies regarding baseline blood pressure determinations and types of control groups, and the possibility of confounding by multiple noncognitive cointerventions (diet, exercise) and expectancy (the placebo effect). In meta analyses involving 1264 patients, differences in mean blood pressure reduction varied according to the duration of baseline blood pressure measurements and type of control groups studied. In 16 comparisons involving baseline periods of more than 1 day, with patients (n = 368) assigned to either a cognitive therapy or a placebo intervention (sham biofeedback, "pseudo-meditation"), systolic and diastolic blood pressures decreased by 2.8 mm Hg (95% CI, -0.8 to 6.4) and 1.3 mm Hg (CI, -1.3 to 3.8), respectively. These changes were neither statistically nor clinically significant. CONCLUSION: Cognitive interventions for essential hypertension are superior to no therapy but not superior to credible sham techniques or to self-monitoring alone. The literature on this subject is limited by a variety of methodologic inadequacies. No single cognitive behavioral technique appears to be more effective than any other. PMID- 8489113 TI - The next patient. PMID- 8489112 TI - Making "connexions": enhancing the therapeutic potential of patient-clinician relationships. AB - Healers must try to understand what the illness means to the patient and create a therapeutic sense of connection in the patient-clinician relationship. A favorable climate for "connexional" experiences can be created through the use of various interviewing techniques. Attending to rapport, silencing internal talk, accessing unconscious processes, and communicating understanding can help clinicians enhance their sensitivity to the subtle clues on which issues of meaning and connection often depend. Several risks are associated with the establishment of closer patient-clinician relationships, including dependence and power issues, sexual attraction, and deeper exposure of the clinician to the patient's pain. Prepared with an awareness of these risks and techniques to address them, clinicians are encouraged to deepen their level of dialogue with patients, to compare their experiences with those of other clinicians, and to thereby develop a more systematic understanding of therapeutic relationships. PMID- 8489115 TI - Cosmetic surgical procedures and connective tissue disease: the Cleopatra syndrome revisited. PMID- 8489114 TI - Is antiretroviral treatment after percutaneous HIV exposure justified? PMID- 8489116 TI - Postoperative hyponatremia in menstruant women. PMID- 8489117 TI - Postoperative hyponatremia in menstruant women. PMID- 8489118 TI - Postoperative hyponatremia in menstruant women. PMID- 8489119 TI - Antibody response to Blastocystis hominis infections. PMID- 8489120 TI - Anticardiolipin antibodies and hypercoagulability. PMID- 8489121 TI - Cyclosporine for thrombotic thrombocytopenic purpura. PMID- 8489122 TI - Changing over-the-counter drugs while retaining the brand name. PMID- 8489123 TI - Call us principal physicians. PMID- 8489124 TI - Dietary cholesterol and plasma lipoproteins. PMID- 8489125 TI - Salt and hypertension: water-sodium handling in essential hypertension. AB - This paper describes sodium handling in the kidney and the significance and mechanisms of its effects upon essential hypertension. In patients with low renin essential hypertension, plasma and urinary norepinephrine levels, plasma renin activity and fractional excretion of sodium were significantly lower, while plasma volume, extracellular fluid volume and exchangeable sodium were higher than in normal renin essential hypertension. The suppression of some renal depressor-natriuretic systems, the dopaminergic, kallikrein-kinin and prostaglandin E2 systems may contribute to the retention of sodium-water in these patients, because these depressor systems were observed to be greatly suppressed in essential hypertension, especially in the low renin group. The reduction of conversion from L-dopa to dopamine by dopa-decarboxylase in the proximal tubules was suggested from our clearance studies as the mechanism of the suppression of renal dopaminergic activity. Moreover, renal dopaminergic activity was already suppressed at the prehypertensive stage, possibly through the inhibition of renal dopa-decarboxylase activity. Thus, it appears that the suppression of renal depressor-natriuretic systems play an important role in the pathogenesis of essential hypertension through the retention of sodium and body fluid volume. PMID- 8489126 TI - The interaction of dietary cholesterol and specific fatty acids in the regulation of LDL receptor activity and plasma LDL-cholesterol concentrations. AB - From these brief considerations, it is clear that the steady-state LDL cholesterol concentration is determined in a powerful way by the interaction of dietary cholesterol and specific fatty acids. There appear to be only a few saturated fatty acids and an even lesser number of unsaturated fatty acids that significantly interact with cholesterol in the liver cell to alter hepatic LDL receptor activity. These effects are uniformly seen in most experimental animals and in humans under circumstances where the experiments are properly designed. Future work is urgently needed to define the metabolic effects of the more unusual fatty acids (e.g., the trans fatty acid) and the more intimate details of how these substances regulate LDL receptor activity in the cell. It is also of considerable importance to extend these studies to the members of the same species that exhibit variable responses to these same dietary lipids. It is now clear that the magnitude of these specific responses to dietary cholesterol and specific fatty acids varies in different individuals with different genetic backgrounds from the same species. Elucidating the reasons for this variability is another area of research of considerable importance to human biology. PMID- 8489127 TI - Dietary salt and blood pressure. PMID- 8489128 TI - Metabolic determinants of low HDL-C levels. PMID- 8489129 TI - Hypo- and hyperresponse of serum cholesterol level and low density lipoprotein production and degradation to dietary cholesterol in man. AB - Serum cholesterol in man rises when cholesterol intake increases, but the extent of the elevation varies between subjects. Part of the variation between subjects is spurious and not reproducible; it is caused by random diet-independent fluctuations of serum lipid levels. Part is due to consistent metabolic differences between subjects. We have earlier found that responsiveness was associated with higher initial total and HDL cholesterol, lower habitual cholesterol consumption, and lower body mass index, and unrelated to gender, age, or apo E phenotype. We have now investigated the metabolic basis of variability by measuring turnover rates of low density lipoprotein (LDL) apolipoprotein B (apo B) on a low-cholesterol diet (140 mg/day) and a high-cholesterol diet (900 mg/day) in 8 volunteers with well-defined differences in the responsiveness of their serum cholesterol to diet. Autologous 125I-LDL was injected on day 23 of each diet period. Its fractional catabolic rate (FCR) was estimated from the ratio of 125I in urine over that in plasma, seven days after injection. FCR (mean +/- SD) increased from 0.24 +/- 0.02 pools/day on the low- to 0.31 +/- 0.20 on the high-cholesterol diet. LDL-apo B concentration rose from 49 +/- 13 to 63 +/- 12 mg/dl, and LDL-apo B production rate, calculated as FCR x concentration/body weight, from 4.8 +/- 1.2 to 8.0 +/- 1.4 mg/kg/day. The individual rise in production rate was significantly correlated with the rise in the serum concentration of LDL-apo B (r = 0.90) or LDL-cholesterol (r = 0.75), and also with the rise in total serum cholesterol measured in these same subjects in similar experiments 3-4 years earlier (r = 0.74). Degradation of LDL by freshly isolated blood mononuclear cells and by mononuclear cells incubated for 72 h in lipoprotein-deficient medium (derepressed cells) was measured on both diets in these and in additional volunteers. The rate of degradation (mean +/- SD) of standard human LDL by fresh cells was 336 +/- 166 ng LDL protein/mg cell protein per 8 h on the low-cholesterol diet, and decreased by 147 +/- 180 ng/mg per 8 h or 44% on the high-cholesterol diet (n = 23, p < 0.01). The catabolic activity of derepressed cells obtained when subjects were on the low-cholesterol diet was negatively related to the LDL cholesterol response (r = -0.57, n = 18, p < 0.05), and to the total cholesterol response in earlier experiments (r = -0.45, n = 18, p < 0.10).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8489130 TI - Dietary protein and experimental atherosclerosis. PMID- 8489131 TI - Soybean protein diet and plasma cholesterol: from therapy to molecular mechanisms. PMID- 8489132 TI - Anti-atherogenicity of soybean protein. PMID- 8489133 TI - Dietary protein and lipid metabolism: a multifunctional effect. PMID- 8489134 TI - The nutrient balance hypothesis: peptides, sympathetic activity, and food intake. AB - Food intake can be increased or decreased after either central or peripheral administration of peptides. Galanin, neuropeptide Y, opioid peptides, growth hormone releasing hormone and desacetyl-MSH increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin releasing hormone, neurotensin, bombesin, enterostatin, cyclo-his-pro and thyrotropin-releasing hormone reduce food intake. A number of these peptides also affect the activity of the sympathetic nervous system. The peptides which have been tested have a reciprocal effect on food intake and sympathetic activity. Opioids, NPY and GHRH, which increase food intake, decrease sympathetic activity. Conversely, peptides which reduce food intake, increase sympathetic activity, with glucagon, cholecystokinin, corticotropin releasing hormone, calcitonin, neurotensin and bombesin being examples, Several of these peptides also affect the intake of specific nutrients. Insulin reduces food intake in animals fed a high carbohydrate diet, but not when fed a high fat diet. Neuropeptide Y increases carbohydrate intake. Galanin and opioid peptides increase fat intake. Enterostatin and cyclo-His-Pro, on the other hand reduce fat intake. Glucagon decreases protein intake. The effect of peptides on the intake of specific nutrients suggests that peptides may work in part by modulating basic feeding mechanisms to lead to the selection of specific nutrients from the diet. This hypothesis might be called a nutrient specific model of peptide-induced food intake. PMID- 8489135 TI - Androgens, the metabolic syndrome, and non-insulin-dependent diabetes mellitus. PMID- 8489136 TI - Genetic differences in adipose tissue metabolism and regulation. PMID- 8489137 TI - Lipid peroxides as the initiating factor of atherosclerosis. PMID- 8489138 TI - Pathophysiology and pathogenesis of visceral fat obesity. PMID- 8489139 TI - Changes of plasma lipids and biochemical markers for coronary artery disease in Korea. AB - The average Korean diet is low in total fat, cholesterol, animal protein, and sugar, and high in total carbohydrate, and adequate in total protein. More foods are derived from vegetables than in any comparable Western countries. The nutritional status of Korean is good without evidence of any gross nutritional deficiency. The leading causes of death, currently, form a unique ranking of malignancies, accidents, and cerebrovascular diseases. Korean diet may account for the strikingly low incidence of heart disease. Studying the relationship between diet and these diseases may greatly aid our understanding of their pathogenesis and lead to improved prevention and treatment. Current changes in the Korean diet are a decreasing proportion of carbohydrates with increasing proportions of fat and animal protein and an increased content of cholesterol. The ratio of polyunsaturated to saturated fatty acid of Korean diet seems to fall in desirable range. The changes in plasma cholesterol levels and CAD mortality among Korean in the past 20 years seem to be a reflection of changes in diet. Similar changes could be seen in the Japanese population. In Korea, the incidence of CAD is still low compared with that in western countries. Recently, a slightly increased incidence of CAD has been observed in Korea. Thus, establishment of reliable biochemical markers and their cut-off values are needed for the Korean population. Several methods including TC, TG, HDL-C, LDL-C, HDL-C/TC, LDL-C/TC, LDL-C/HDL-C, Apo A-I, Apo B and Apo A-I/B for CAD were examined and found that Apo A-I/B ratio was a good biochemical marker for CAD in Korea. In the future, the Korean diet will probably continue to change. The changes are being influenced by economic development that have been emerging and growing stronger since 1980 and that will probably continue to be potent. The effect of these changes upon CAD is not clear at the present time. To detect a changing incidence of CAD and to evaluate the significance of diet will require continued close observation and use of more specific and sensitive methods. The Korean experience with diet and plasma lipids will be potentially valuable in appraising CAD of both developing and technically developed countries. PMID- 8489140 TI - Complexities of national recommendations for the dietary prevention of coronary heart disease. PMID- 8489141 TI - Age-related loss of bone mass and aortic/aortic valve calcification--reevaluation of recommended dietary allowance of calcium in the elderly. PMID- 8489142 TI - Trace elements in cardio-cerebrovascular diseases. PMID- 8489143 TI - Hypotensive effect of soy protein and its hydrolysate. PMID- 8489144 TI - Serum lipids and nutritional intake in a Japanese general population: the Hisayama Study. PMID- 8489145 TI - The relationship between coronary artery diseases and magnesium deficiency, with regard to coronary artery spasms. PMID- 8489146 TI - Effects of sesamin on serum lipoprotein metabolism in normocholesterolemic and hypercholesterolemic stroke-prone SHR. PMID- 8489147 TI - Trace elements and ischemic cerebral vascular disease. PMID- 8489148 TI - Glucose tolerance, obesity, and hypertension: epidemiological study in Hokkaido, Japan. PMID- 8489149 TI - Insulin sensitivity and renal sodium-water metabolism in obese normotensive subjects. PMID- 8489150 TI - Discovery of a new diet for patients with acute myocardial infarction: an Indian experiment on infarct survival. PMID- 8489151 TI - A fat meal test is useful to recognize the background of hyperlipidemia. PMID- 8489152 TI - A simple method for measuring urinary sodium and potassium excretion in field surveys and its application to epidemiological studies. PMID- 8489153 TI - Effect of soy protein on the excretion amount of fecal sterols in Jcl:Wistar rats. PMID- 8489154 TI - Ultrastructural and biochemical evidence of cardiac lipofuscinosis after short term intake of fish oil in rats. PMID- 8489155 TI - Eicosanoids and health. PMID- 8489156 TI - The influence of dietary n-3 fatty acids on plasma lipids and lipoproteins. AB - The body of epidemiologic data indicates that the incidence of cardiovascular disease is lower in populations whose habitual diet is rich in fish. It is unclear however to what extent this apparent protection is due to the intake of n 3 fatty acids in sea food or to the fact that these subjects have generally been consuming lower amounts of saturated fatty acids in their diets. It is clear, however, that when the dietary intake of n-3 fatty acids is increased to 4-8 g/day distinct metabolic effects are observed, including reductions in plasma triglycerides, effects on platelet function and coagulation factors and blood pressure. Larger intakes exert a more profound hypotriglyceridemic effect, and in patients with primary hypercholesterolemia daily intakes exceeding 10-12 g/day are effective in reducing plasma concentrations of LDL cholesterol. However, from a practical point of view, the lipid-modifying effects of supplemental dietary n 3 fatty acids are most clearly observed in patients with hypertriglyceridemia and the major usefulness of dietary n-3 fatty acids is in the treatment of this patient population, particularly patients with severe hypertriglyceridemia or potentially those with Type III hyperlipoproteinemia. Further studies are needed to better define the potential utility of dietary n-3 fatty acids when used in combination with lipid-lowering drugs to reduce lipoprotein concentrations in patients with combined hyperlipoproteinemia or severe hypertriglyceridemia. PMID- 8489157 TI - The influence of docosahexaenoic acid loading on stroke-prone spontaneously hypertensive rats. PMID- 8489158 TI - Vegetarian diets, alcohol consumption, and hypertension. PMID- 8489159 TI - Hypertensive cerebrovascular diseases: importance of nutrition in pathogenesis and prevention. PMID- 8489160 TI - Particle repositioning maneuver for benign paroxysmal positional vertigo. AB - Benign paroxysmal positional vertigo is a common, most often self-limited, vestibular end organ disorder that in some cases may be quite disabling. Recent evidence suggests that some, if not most, cases result from free-floating posterior semicircular canal endolymph particles. We postulate that the particle repositioning maneuver displaces these particles from the posterior canal through the common crus into the utricle, where they no longer induce pathologic responses. Our report focuses on 38 consecutive patients treated with this simple bedside technique during a 10-month period. On follow-up, 26 patients (68.4%) were free of disease, 4 (10.5%) were significantly improved, 4(10.5%) remained unchanged, and 4(10.5%) were lost to follow-up. Of the 4 patients who remained unchanged, 2 underwent successful posterior semicircular canal occlusions. The direction of the nystagmus during the second stage of the maneuver appears important in predicting the efficacy, with reversal of nystagmus denoting a poor response. These findings provide additional insight into the pathophysiology of this disorder. PMID- 8489161 TI - Esophageal stricture following esophageal atresia repair: endoscopic assessment and dilation. AB - A retrospective review from 1981 to 1986 was made of 51 neonates who were treated for congenital esophageal atresia at the Royal Alexandra Hospital for Children, Sydney, Australia. Thirty of the 51 had primary repair and 15 (50%) developed esophageal stricture requiring one or more dilations. Stricture dilations were performed with open-tube rigid esophagoscopes, rigid telescopes, and Jackson dilators. The number of dilations performed until the patient was asymptomatic ranged from 1 to 12 (mean 4.5). The minimal follow-up time was 4 years. There was one esophageal perforation with full recovery following conservative management. One child died of septicemia caused by continued aspiration of unknown cause. A surprising finding, contrary to other reports, was the stricture formation did not appear to be related to the size of the "gap" found at the time of esophageal repair. Gastroesophageal reflux, however, was an important factor. We conclude that esophageal stricture following repair of tracheoesophageal atresia can be satisfactorily and relatively safely managed by direct vision antegrade endoscopic dilation using graduated dilators, although treatment may be prolonged and repeated. New esophagoscopes and dilators, in graduated sizes and designed for pediatric use, are recommended. The technique of esophageal dilation in infants is described in detail. Pediatric laryngobronchoesophagologists will become more involved in the care of infants born with esophageal atresia with or without tracheoesophageal fistula. PMID- 8489162 TI - Early diagnosis of otologic Wegener's granulomatosis using the serologic marker C ANCA. AB - Wegener's granulomatosis is a systemic vasculitis that may involve any organ system. Otologic manifestations are common, and can be the presenting complaint. In the past, diagnosis often necessitated the development of characteristic pulmonary or renal disease. The identification of a new serologic marker, cytoplasmic pattern antineutrophil cytoplasmic autoantibody (C-ANCA), allows for the early diagnosis of Wegener's granulomatosis and gives the patient the best chance for remission with cytotoxic therapy. We report two patients with Wegener's granulomatosis who presented with refractory otitis media, one of whom subsequently developed facial nerve paralysis, in which an early diagnosis was facilitated by the use of the C-ANCA test. Otologic manifestations of Wegener's granulomatosis and the basis of the C-ANCA test are discussed. PMID- 8489163 TI - Conversion deafness. AB - Conversion deafness is very rarely encountered among adults. This report will illustrate two cases of this somatoform disorder following different traumatic experiences. It emphasizes the difficulties in establishing the diagnosis and reviews various aspects of treatment. PMID- 8489164 TI - Composition of the otosclerotic stapes: electron microprobe analyses. AB - For the first time, otosclerotic stapes have been distinguished from unafflicted controls at a high level of significance by using a spectrum of elements measured by energy-dispersive spectrometer-electron probe microanalyses (EDS/EPMA). Discriminant analyses of the maximum concentration of 13 elements measured at several sites within each of 32 stapes differentiated otosclerotic from unafflicted individuals well above the 95% confidence level. Eight of the 9 control (unafflicted) and 21 of the 23 afflicted stapes were correctly classified. In descending order of contribution to the discriminant function, the elements are Zn > Cr > K > Ca > Si > Mn > Na > Al > Mg > P > Fe > S > Ti. Zinc and chromium account for much of the difference, but discriminant analyses excluding them still distinguish the two groups at the 95% confidence level. These results are consistent with previous reports of high levels of alkaline phosphatase, a zinc-containing enzyme, in afflicted stapes. But the broad spectrum of elements capable of distinguishing otosclerotic stapes warrants study of additional zinc-containing and other metal-containing or metal-activated moieties. PMID- 8489165 TI - Neuro-otologic abnormalities in myelopathy associated with human T-cell lymphotropic virus type 1. AB - Auditory testing (pure tone audiometry, auditory brain stem response), and vestibular tests (eye tracking test, optokinetic pattern test, and caloric test) were performed to define neuro-otologic abnormalities in myelopathy associated with human T-cell lymphotropic virus type 1. Of the eight patients tested, seven showed sensorineural hearing loss and one showed mixed hearing loss on pure tone audiometry. The auditory brain stem responses of five patients showed increases of the I-III and I-V interpeak latencies. Two patients showed fast superimposed saccadic movements on the smooth pursuit test, and one other patient showed canal paresis on the caloric test. These findings suggest both the presence of neuro otologic abnormality and involvement of the brain stem in myelopathy associated with human T-cell lymphotropic virus type 1. PMID- 8489166 TI - Comparison of half-band and full-band electrodes for intracochlear electrical stimulation. AB - It was hypothesized that intracochlear stimulating electrodes oriented toward the modiolus would require a lower stimulus current to elicit a threshold neural response than longitudinal band electrodes. Electrically evoked auditory brain stem responses (EABRs) and electrode impedances were recorded with full-band and oriented half-band scala tympani electrodes in anesthetized, deafened cats. To elicit a threshold EABR, the stimulus current required for stimulation through half-band electrodes oriented toward the modiolus was not significantly different from the current required for stimulation through full-band electrodes. The impedances of full-band electrodes were significantly lower than those of half band electrodes. Considering the significantly higher impedance and current density of half-band electrodes in comparison to full-band electrodes, as well as the critical orientation of half-band electrodes during implantation, we believe that full-band electrodes have advantages over half-band electrodes for scala tympani implantation. PMID- 8489167 TI - Immunohistochemical localization of a cytochrome P-450 isozyme in human nasal mucosa: age-related trends. AB - Immunoperoxidase staining with an antibody to cytochrome P-450 (NMa) was used to investigate the localization of this isozyme in the human nasal mucosa. Olfactory mucosa was identified by staining of olfactory receptor cells with an antibody to olfactory marker protein. Immunoreactivity to NMa was localized in sustentacular cells in the olfactory epithelium, and in Bowman's gland acinar cells and vascular endothelial cells in the lamina propria. In the respiratory mucosa, ciliated epithelial cells, as well as serous gland acinar cells and vascular endothelial cells in the lamina propria, were immunoreactive for this isozyme. An age-related decrement in the intensity and extent of immunoreactivity within these cells was noted in nasal tissue from patients 60 years of age and over when compared with that of patients under 60 years of age. These results identify sites of xenobiotic metabolism or activation in human nasal mucosa. PMID- 8489168 TI - Bilateral parotid duct fistula. Case report. AB - Parotid duct fistulas (PDFs) are rare and have various causes such as gunshot wounds and human and animal bites; they may also be congenital. We have not found previous publications on bilateral PDF. Our patient, although young, also had generalized pigmentation characteristic of aging and thick, dry, wrinkled skin, as well as pyoderma. Biochemical analysis was performed on discharge from the patient's face, and histopathologic and immunologic studies were done. The fistulas were treated by intraoral fistulization. Cephalosporins were given to the patient for 5 days postoperatively to treat the pyoderma. PMID- 8489169 TI - Effects of stellate ganglion stimulation on bilateral cochlear blood flow. AB - The effect of intraneural electrical stimulation of the stellate ganglion (SG) on bilateral cochlear blood flow (CBF) was investigated with laser-Doppler flowmetry. The SG of 15 anesthetized guinea pigs was exposed by a novel surgical approach and stimulated with a specially designed intraneural bipolar platinum iridium electrode. Bilateral CBF was continuously monitored. Stimulation of 0.25 mA caused a detectable increase of the systemic blood pressure (BP) and a bilateral decrease of the cochlear vascular conductance (R, defined as the ratio CBF/BP). A stimulus of 0.5 mA elicited a statistically significant ipsilateral CBF (CBFi) decrease of 3.6% +/- 5.1% from the baseline and a contralateral CBF (CBFc) decrease of 3.1% +/- 5.5%. That no statistical difference was found between CBFi and CBFc indicates that a unilateral sympathetic stimulation of the SG can cause equal bilateral responses. These responses were accompanied by a significantly increased BP (8.7% +/- 5.2% of baseline) and consequently a greatly decreased R (12.2% +/- 6.5%) of the ipsilateral cochlea. Bilateral sections of the cervical sympathetic trunk below the level of the superior cervical ganglion did not alter the evoked changes in CBF, BP, and R. It is concluded that SG stimulation can decrease the conductivity of the cochlear vessels or the supplying vessels of the cochlea. Additionally, the SG nerve fibers that cause these effects do not pass through the superior cervical ganglion. PMID- 8489170 TI - Development of secretory elements in murine tubotympanum: lysozyme and lactoferrin immunohistochemistry. AB - Secretory activity, particularly of antibacterial agents such as lysozyme and lactoferrin, is an important aspect of the mucosal defense mechanism, and the development of these agents may have a direct bearing on the susceptibility of the ear to infection. In this study, the secretory cells of the murine tubal epithelium were first observed at gestational day 17. Although tubal glands began to develop on gestational day 18, their secretory activity was first shown on postnatal day 3. The number of secretory cells of the tubal epithelium increased rapidly immediately after birth, while that of the tubal glands showed a gradual increase from postnatal day 3. The epithelial secretory cells in the tubotympanum matured at birth, but the tubal glands matured gradually after birth. Lysozyme was first recognized in the epithelial secretory cells on postnatal day 1, while lactoferrin was first detected in the tubal glands on postnatal day 3. Both lysozyme and lactoferrin were co-localized in the serous cells of the tubal glands. The secretion of lysozyme and lactoferrin seemed to reflect the maturation of the secretory cells in the murine tubotympanum. PMID- 8489171 TI - Combined (external and internal) laryngopyocele. PMID- 8489172 TI - Osteoma arising from the stylohyoid chain and manifesting as a neck and oropharyngeal mass. PMID- 8489173 TI - Tall cell carcinoma of the thyroid gland. AB - Tall cell carcinoma of the thyroid gland is an aggressive variant of papillary carcinoma with a respectable 20% to 25% lethality. Its histologic features are characterized by a basal orientation of nuclei, abundant eosinophilic or oxyphilic cytoplasm, and a cellular height-width ratio greater than 2:1. These distinguish it from another aggressive variant, columnar cell carcinoma, which has a stratification of its nuclei and scant cellular cytoplasm. PMID- 8489174 TI - Superiority of the fasciocutaneous flap in reconstruction of sacral pressure sores. AB - The gluteal maximus muscle has been used in the treatment of sacral pressure sores since the 1970s. However, it is noted that the muscle portion of the transferred flap shows highly atrophic degeneration and the muscle itself is not suitable tissue for covering the pressure-bearing area. We have managed various fasciocutaneous flaps as the first choice for reconstruction of sacral pressure sores and obtained good results. The fasciocutaneous flap has an anatomical structure that resists physical stimulation or external pressure and an abundant blood supply via its fascial plexus. In addition, if we use a gluteal maximus myocutaneous flap at first, some fasciocutaneous flaps are compromised because of the design and blood supply. We suggest that the fasciocutaneous flap has the first priority and is superior to the gluteal maximus myocutaneous and muscle flaps in reconstruction of sacral pressure sores. PMID- 8489175 TI - A newly designed minigraft to achieve angularity and projection of the nasal tip: the asymmetrical bipyramidal graft. AB - A new systematization for onlay tip grafting is described, using a minigraft constructed from either irradiated, glutaraldehyde-processed bovine cartilage or soft-grade silicone blocks. The graft design consists of two pyramidal volumes amputated in the apex and carved with mild concave surfaces. The lateral profile of the graft is asymmetrical with an acute inclination in the front and a slight inclination in the back. The graft height ranges from 1.5 to 3.8 mm. With this type of implant, high tip projection with a natural appearance can be achieved easily. Since 1986, we have performed 39 tip implants (12 cartilage grafts and 27 silicone grafts). Silicone graft fate has been excellent with no complications, whereas cartilage grafts underwent a 25% resorption rate. Thus, the current technique is now solely undertaken with silicone minigrafts. Main indications are primary tip plasty in normal-size noses with poor tip projection, and secondary noses. This technique is not recommended for simultaneous use with primary rhinoplasty. For more than 4 years, this technique has provided consistent results, being highly effective in achieving the objective of increasing tip projection. PMID- 8489176 TI - Futility of muscle flaps for self-inflicted wounds. AB - Unacceptable forms of self-mutilation usually are resistant to surgical intervention and have a basis in psychopathology. Establishing this diagnosis may be as difficult as is the treatment, frequently involving a prolonged process of exclusion of other known disease entities. Management of these chronic self inflicted wounds demands flexibility by the surgeon who must be aware of this possibility and willing to deviate from the normal approach to wound healing. Simplicity is of paramount importance. The use of vascularized tissues and, in particular, the sacrifice of scarce muscle flaps probably is unwarranted except as a last resort because these wounds nevertheless remain recalcitrant to permanent healing. Instead, a nonconfrontational approach with long-term psychotherapy should be a major part of the initial therapy with surgery considered only important in an adjunctive role. PMID- 8489177 TI - Surgical treatment of axillary osmidrosis. AB - Various types of surgical procedures have been developed for treatment of axillary hyperhidrosis and osmidrosis. However, Asian people tend to seek treatment for osmidrosis rather than hyperhidrosis. In this article, we report a new modified surgical method concerning axillary osmidrosis. At first we make four transverse parallel incisions; two incisions in the center are large (approximately 4 cm in length) and the lateral ones are small (approximately 1.5 cm in length). Then, we do enough undermining from the four wound edges to make a wide subcutaneous tunnel, and the adipose tissue beneath the skin is removed with scissors through each incision. Finally, two pieces of Penrose drain are inserted through the small lateral incisions. With this method we have operated on 21 patients in the past 3 years; 19 patients were female, and only 2 were male. Patients were followed for a minimum of 3 months and a maximum of 22 months, with an average follow-up of 7 months. In terms of results, 14 were good, 5 fair, and 2 poor. Minor complications such as partial epidermal necrosis occurred in only 2 patients, but healed with conservative treatment, and other complications such as hematoma formation or infection did not occur. In this article, we emphasize two merits of our procedure. One is that adding small incisions at both lateral margins makes it possible to perform the further excision of the apocrine glands. The other merit is that drainage from the small incisions is very effective. We believe this procedure is a viable option for treatment of axillary hyperhidrosis and osmidrosis. PMID- 8489178 TI - Immediate free tissue transfer for distal musculoskeletal neoplasms. AB - Sarcomas and other aggressive neoplasms of the extremities present particular challenges for limb salvage when the tumors are located distally in the arms or legs. These tumors require a large area of excision, yet there are no suitable options for local tissue coverage. In the past, amputation was often necessary due to the inability to adequately reconstruct the extremity. We performed immediate free tissue transfers on 10 patients with aggressive tumors in the forearm and lower leg. Eight patients had sarcomas, 1 had a melanoma, and 1 had a recurrent fibromatosis. Seven patients had rectus abdominis flaps, 1 had a latissimus dorsi flap, 1 had a groin flap, and 1 had an osteocutaneous flap from the iliac crest. Three patients had tendon transfers at the time of surgery. Four patients required radiation therapy after resection due to the high-grade nature of their neoplasms. The flaps tolerated the radiation well, with only 1 patient sustaining flap necrosis that required skin grafting. Average follow-up was 28 months. All patients are alive and none had local recurrences of their tumors. All free flaps have survived and remained durable. There have been no late breakdowns of skin grafts, and all tendon transfers have functioned well. Immediate free tissue transfer provides an excellent method of reconstruction for distal tumors of the extremities. PMID- 8489179 TI - Walking track analysis: utilization of individual footprint parameters. AB - Functional assessment of rat sciatic, tibial, and peroneal nerve injuries was performed using walking track analysis. Individual walking print length (PL), toe spread (TS), and intermediate toe spread (ITS) values were measured up to 24 weeks after specific nerve transection, with or without repair. Sciatic and tibial nerve manipulation initially affected all footprint measurements, consistent with loss of intrinsic and extrinsic motor function. After sciatic repair, TS demonstrated partial recovery without any substantial recovery in PL or ITS, compared with sciatic transection values. By contrast, after tibial repair, PL values recovered dramatically, between 16 and 24 weeks, to levels not significantly different from control subjects. This was not observed after tibial transection without repair. TS recovered partially, whereas ITS recovered to control levels by 20 weeks after tibial repair. Peroneal transection resulted in multiple contractures, rendering this group unmeasurable at 4 weeks. After peroneal repair, only the PL reflected significant loss of function at 2 weeks, recovering to control values by 8 weeks. Manual TS measurements in nonwalking rats did not reflect functional nerve regeneration. Thus, individual PL measurements alone can be used to characterize functional recovery after tibial and peroneal nerve injury, whereas TS reflected recovery after sciatic nerve injury. PMID- 8489180 TI - Augmentation of skin flap survival by selective intraarterial infusion of prostaglandin E1: experimental and clinical studies. AB - Prostaglandin E1 has been proven to be useful in the treatment of vascular diseases of the lower leg. Plastic surgeons have been aware of its usefulness in augmenting flap survival and have used it intraarterially or intravenously. We attempted to enhance the effect of prostaglandin E1 with heparin by local continuous intraarterial infusion of both drugs. First, we assessed the viability area of an experimental island flap model on rabbit abdomen, and confirmed the usefulness of this method. Next, we attempted to develop clinical cases using Seldinger's method. By this method, we were able to rescue the flaps with circulatory insufficiency and gain a larger survival area of an axial pattern flap. PMID- 8489181 TI - Reconstruction of a medial canthus defect with a myocutaneous flap. AB - Defects in the inner canthal area are generally repaired by full-thickness skin grafts, V-Y advancement flap, or frontal flap. Each of these techniques may give some problems in restoring the functional or aesthetic features of that region, or both. To avoid these inconveniences, we performed the reconstruction of the medial canthal area after tumor excision by using a myocutaneous rotation flap from the upper lid joined to a rotation flap from the lower lid and cheek. No scar resulted inside the aesthetic unit and a fine result was achieved from both the functional and the aesthetic point of view. PMID- 8489182 TI - Congenital bilateral intermaxillary bony fusion. AB - Congenital fusion of maxillary and mandibular alveolar margins is extremely rare. Bony fusion between the jaws is still more uncommon. Only eight patients with bony fusion have been described in the literature to date, of whom only three had bilateral bony fusion. We present here a patient with very extensive bilateral bony fusion of the jaws, who underwent surgery with excellent immediate postoperative results. Details of the surgical management of this rare and difficult problem in a neonate with poor general condition are described. PMID- 8489183 TI - Free lateral calcaneal flap. AB - Our cadaver dissection demonstrated that the lateral calcaneal artery is large enough for microsurgical anastomosis. Based on the finding, the lateral calcaneal flap was first successfully applied as a free flap that included the lesser saphenous vein and the sural nerve in the pedicle. This thin sensory flap, dispensing with main arterial damage, is indicated for the lesion of the posterior heel, plantar, and hand. PMID- 8489184 TI - Closure of myelomeningocele using skin from stillborn twin. AB - We report a case of homologous skin transplantation from a stillborn twin to the surviving twin for coverage of a myelomeningocele defect. Genetic studies were not available preoperatively, however, similar morphogenetic anomalies of the twins suggested monozygosity. Long-term follow-up revealed a well-healed graft. Cutaneous genetics and literature review of twin homologous skin transplantation are presented. PMID- 8489185 TI - A latissimus/scapula combined myo-osseous free flap based on the subscapular artery used for elbow reconstruction. AB - A myo-osseous free tissue transfer based on the subscapular artery provided elbow reconstruction after a shotgun injury. This reconstruction offers a durable and stable form of soft tissue and bone, preventing some arm function. The tailoring of the latissimus dorsi muscle and the modification of not dividing the teres major in the microvascular harvest offers donor site functional preservation. Although the dissection is more tedious, preservation of the teres major permits minimal donor morbidity, maintenance of function, and the ideal reconstruction of soft tissue and bony loss. PMID- 8489186 TI - Use of the temporal muscle flap in Barraquer-Simon's progressive lipodystrophy. PMID- 8489188 TI - The view from the bridge. PMID- 8489187 TI - A simple technique for harvesting standardized skin grafts in the rodent. AB - A simple technique for harvesting skin grafts of predetermined size, shape, and thickness in rodents is described. In this technique, the donor skin is immobilized and tensed by means of a tongue depressor, or similar template, inserted into the loose areolar tissue below the panniculus, stretching the overlying skin to permit easy dermatome harvesting of a skin graft. PMID- 8489189 TI - Re: Recombinant human platelet-derived growth factor-BB for the treatment of chronic pressure ulcers. PMID- 8489190 TI - Reconstruction of the lower extremity after grade III distal tibial injuries using combined microsurgical free tissue transfer and bone transport by distraction osteosynthesis. AB - Five patients each with grade IIIB or IIIC distal tibial injuries are presented. All patients were treated initially by multiple debridements and external fixation of the tibial fracture. After failure of the primary treatment, each patient underwent microsurgical free muscle transfer and bone transport of the proximal tibia to reconstruct the lower leg. Soft tissue loss ranged from 8 to 20 cm. Segmental tibial loss ranged from 8 to 18 cm. Free flaps used included rectus abdominis, latissimus dorsi, and combined latissimus dorsi-serratus anterior muscles. Bone transport was accomplished by callus distraction after corticotomy. All patients are ambulatory, fully weight bearing, and without pain (range, 17-34 mo). This treatment method has obviated the need for below-the-knee amputation in all of our patients. PMID- 8489191 TI - [Neuroma of the common bile duct]. AB - After a surgical operation on the biliary tract, stenoses can occur, most of the time due to fibrotic lesions, and more rarely due to granulomas or traumatic neuromas. The latter generally develop on the cystic stump after a cholecystectomy. The occurrence of a traumatic neuroma on the common bile duct is much more rarely described. We report the case of a 64 year-old man presenting, four years after a surgical removal of the gallbladder, with a cholangitis, due to neuroma located on the choledochus. He was treated by surgical resection of the common bile-duct at the site of the stenotic zone, and choledocojejunal anastomosis; post-operative course was satisfactory. PMID- 8489192 TI - [The value and limitations of biofeedback in ano-rectal pathology]. AB - Biofeedback, an instrumental training technique, enables the understanding and correction of a physiological mechanism, anorectal function in the present case. Correction of a functional abnormality seen as being responsible for a symptom involves the interplay of several factors within biofeedback, in particular the link between symptoms and functional abnormalities and the relationship existing between the trainer and trainee, the relative importance of which is difficult to identify. Initiation of such rehabilitation requires full clinical and functional evaluation in order to determine the indications and type of training programme required. Terminal constipation and incontinence are the chief indications providing useful results. This technique must be envisaged in the context of global management of perineal status as a whole, concomitantly with medical and surgical treatment. PMID- 8489193 TI - [Pharmacokinetics and therapeutic monitoring of cyclosporine in liver transplant patients]. AB - Cyclosporine (CsA) has played a major role in the development of organ transplantation. However, its use in the prevention of liver graft rejection is somewhat delicate because the liver plays an essential role in the intestinal absorption, metabolism an excretion of CsA. Interindividual differences in CsA pharmacokinetics are large, and clearance can vary by a factor of 40 in liver transplant recipients. During CsA therapy, the intact molecule is assayed in whole blood by means of specific technique. The margin between immunosuppressive and nephrotoxic concentrations is poorly defined. The interpretation of blood concentrations must take into account the mode of administration, associated drug therapy, the time since grafting, and pathological episodes. The recommend through concentrations are 150-200 ng/ml during the first three months. PMID- 8489194 TI - [Endo-brachyesophagus, Jean-Louis Lortat-Jacob and the Barrett esophagus. The history of a modern disease]. AB - The term endo-brachyoesophagus (EBO) became part of the specialised vocabulary of all those interested in the pathology of the esophagus at the beginning of the 1950s, when J.L. Lortat-Jacob identified the existence, in certain patients suffering from reflux, of the endoesophageal ascent of a mucosa of gastric type, without any change in the gross topography of the gastro-esophageal junction. A similar lesion had been described at this same time in Great Britain by N.R. Barrett. Since then, numerous clinical and experimental arguments have been advanced in support of the acquired origin of this disorder, in the context of progressive gastro-esophageal reflux disease. However, the possibility of its regression after the treatment of reflux and its histologic presentation, though of major importance, remain unsettled. It is now generally acknowledged that EBO is one of the digestive lesions most prone to malignant degeneration, to the extent that it is now generally classified as precancerous, and all the most sophisticated procedures have been currently suggested and exploited in the attempt to detect EBO of potential malignancy. Within this field, ultramicroscopic study, enzyme assays and the techniques of flow cytometry are being used to better define this problem and to specify the point after which it is legitimate to abandon the medical treatment of reflux in favor of more aggressive methods, even surgical resection of the esophagus. The OESO Group, created in 1978, is currently conducting an international multidisciplinary and multicenter study to deal with the epidemiologic and therapeutic problems of this disorder. PMID- 8489195 TI - [Ethical and social problems posed by organ transplantation]. AB - Organ transplantation more than a scientific fact is now a social fact. Since the first organ transplantations in France, forty years ago, medicine demonstrated its ability to perform the operation and to obtain (what was more difficult) the tolerance of the graft but medicine so far remains unable to give the material: organs. These organs are given by the donor's relatives when the kidney is concerned and when it is a donation from a living person. But such donation remain strictly limited in our country (less than 5 p. cent of the kidney transplantations) due to the risk of moral pressure and commercialization. More often and for the other organs (liver, heart, lung) the donation is obtained after death, a special and dramatic death: the brain death. The nowadays spectacular results of organ transplantation 70 to 80 p. cent survival rate at 10 years with a complete rehabilitation gave a considerable increase on the demand. Unfortunately organ transplantation is the victim of its success, the number of donor's organ being insufficient to satisfy the needs. So in December 1990, 6,055 patients were on the waiting list and only 3,772 (56 p. cent) were transplanted. In December 1991, 6,334 patients were on the waiting list and may be only 4,000 could be transplanted. So the difference between the needs and the possibilities is increasing each year with for consequences, the death of 10 p. cent of the waiting patients and, for those who could be transplanted, a considerable increase in the waiting period responsible for slow deterioration of their status and less chances of success.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489196 TI - [Adjuvant treatment of patients with neoplastic lesions using the combination of a vitamin complex and an amino acid. Apropos of a series of 17 cases of epidermoid carcinoma of the upper aerodigestive tract]. AB - The aim of the work reported here was to evaluate the effects of an adjuvant treatment composed of an association of vitamins with an amino acid: beta alanine, in cancer patients. This adjuvant therapy has been given to 17 subjects with a squamous cell carcinoma of upper aerodigestive tract treated by radiotherapy most cases were T3 (according to the TNM-UICC). After a 63 months follow-up, 7 patients are alive and sterilized, 4 are alive but no sterilized, 2 died, 4 were excluded from the study. Besides a physical comfort improved in all our patients, we note a restoration of the immune defenses, both humoral and cellular, disturbed by radiotherapy. At last, we note an increase of survival in the patients treated by the adjuvant therapy, compared to a reference population of patients with squamous cell carcinoma of upper aerodigestive tract. Despite the limits of the study, it was interesting to report the positive effects of the therapeutical association, vitamins and beta-alanine, after a combined radio surgical treatment of patients with squamous cell carcinoma of upper aerodigestive tract. PMID- 8489197 TI - Genetic structure of human populations in the British Isles. AB - Spatial patterns were studied for 36 allele frequencies representing 14 genetic systems (blood antigens, enzymes and serum proteins) in the United Kingdom and Irish Republic. The total number of data points over all systems and localities is 331. Patterns of genetic variation in space are graphically represented by one dimensional and directional correlograms, and by interpolated allele-frequency surfaces. The data surfaces were examined by the various techniques of spatial autocorrelation analysis. Zones of rapid change across allele surfaces were discovered by the wombling method. Six allele frequency surfaces from four genetic systems exhibit significant spatial patterns. Only one pattern (IO; in the ABO system) may be described as purely clinal in an east-west direction; another (IB; in ABO) approximates a cline or at least north-south differentiation. A method was developed for testing the direction of maximal genetic autocorrelation. Two previously unrecorded patterns for the British Isles, north-south gradients for Rhesus and P, were detected. Twelve zones of rapid genetic change were discovered; some of these seem to reflect maritime and montane physical barriers as well as long-held cultural and linguistic differences, particularly between early Germanic and Celtic speakers. Moreover, some appear to reflect past historic events such as the invasions of Anglo-Saxons and Anglo-Normans. PMID- 8489198 TI - Correlations of birth weight and gestational age across generations. AB - Maternal birth weight is known to be a predictor of offspring birth weight. Less is known about the recurrence of gestational age. In order to estimate the recurrence risk of low birth weight and preterm birth across generations in a population-based sample, 11,092 pairs of mother-firstborn offspring were obtained through an internal linkage in the Norwegian Birth Registry based on the years 1967-1969 (mothers) and 1986-1989 (offspring). A low correlation coefficient of 0.086 was found for gestational age across generations, whereas the correlation between maternal and offspring birth weight was 0.242. Mothers with birth weight below 2500 g had a significantly increased risk (odds ratio = 3.03, 95% conf. interval 1.79-5.11) of having a low birth weight child compared with mothers with birth weight above 4 kg. On the other hand, if the mother was born before the 37th completed week of gestation, the risk of having a preterm child was not significantly increased (odds ratio = 1.46, conf. interval 0.96-2.21) compared with mothers who were born at term. Thus, in contrast to birth weight, human variation in gestational age does not appear to be influenced by genetic factors to any large degree. PMID- 8489199 TI - The dynamics of growth of weight, circumferences and skinfolds in distance, velocity and acceleration. AB - Based on structural average curves of distance, velocity and acceleration, an analysis of the longitudinally assessed growth of weight, arm and calf circumferences and skinfolds (biceps, triceps, suprailiac, subscapular) was undertaken. The data come from the first Zurich longitudinal growth study and represent a normal sample. In addition to a graphic analysis, timing, intensity and duration of the mid-growth spurt (MS) and of the pubertal spurt (PS) are quantified via descriptive parameters of growth. Mechanisms are different and more complex for these variables, in particular for skinfolds, compared to previously studied somatic variables, such as height. Skinfolds showed a rapid decline to a negative velocity minimum in the first year, recovering to a pre-PS fat spurt, earlier and more pronounced for central (suprailiac, subscapular) than for peripheral skinfolds (biceps, triceps). At age of peak height velocity a drop occurred, stronger for boys, followed by a post-PS spurt. A further analysis demonstrates that these ups and downs in skinfold velocity are mainly due to subjects with thick skinfolds. Weight and circumferences show a distinct MS, with sex-independent characteristics and a strong, sex-dependent PS. Weight and even more arm circumference are delayed compared to height in puberty. PMID- 8489200 TI - Microevolution in Perugia: isonymy 1890-1990. AB - The distribution of surnames in the population of the Comune of Perugia, as it existed in the memory banks of the Municipality Computer in autumn 1991, was studied by age and place of birth. Fisher's alpha and Karlin-McGregor's v were estimated in the total population, in persons born before 1901, and in persons born in the nine decades thereafter, ending with the period 1981-1991, for immigrants and for natives of Perugia, respectively. The wealth of surnames was significantly higher in immigrants than in natives of Perugia, as detected by alpha, v and by the log-log regression of the corresponding distributions. Among residents born in Perugia, Fisher's alpha shows a minimum value during 1921-1930, explained as a consequence of the First World War. The relationship between all possible combinations of cohorts born in the 10 different decades was studied through the Euclidean distance and through Lasker's coefficient of relationship, and a significant correlation between the former and time was revealed, both in immigrants and in natives of Perugia. When compared with the Province of Ferrara, Perugia was far richer in surnames, as measured by Fisher's alpha, for the total population and for each of the 10 decades analysed. Recent immigration, measured by Karlin-McGregor's v, was significantly higher in Perugia until the 1960s, equal in both Provinces during the 1970s, and higher in Ferrara during the 1980s. PMID- 8489201 TI - Body fat distribution in men and women of the Hispanic health and nutrition examination survey of the United States: associations with behavioural variables. AB - Body fat distribution is a biological risk factor for cardiovascular disease and diabetes. There are known genetic factors influencing body fat distribution, but variation in this characteristic is also attributable to human behavioural and socioeconomic variables such as social class. Bjorntorp has proposed that these associations may be due to a series of physiological responses to psychosocial stress, most prominently chronic stimulation of the adrenal-cortical system. This system is known to affect body fat distribution. Elsewhere we have shown that general socioeconomic status is related to body fat distribution in men and women of the Hispanic Health and Nutrition Examination Survey (HHANES) of the United States. In this paper we explore the relationship with those behavioural variables available from the HHANES which could hypothetically serve as indicators of psychosocial stress: smoking, drinking and depression. For both sexes in all Hispanic ethnic groups except Puerto Rican men, as socioeconomic status declined, subcutaneous fat became more centrally distributed. This relationship continued to be significant after controlling for the behavioural variables. A positive relationship was also found between smoking and central body fat distribution which was independent of socioeconomic status. This relationship was statistically significant for all subsamples except Cuban American women. No consistent relationships were found between body fat distribution, drinking and depression. The data support the hypothesis that body fat distribution may be linked to the social stress of low socioeconomic status, independent of the behavioural factors tested. PMID- 8489202 TI - Skin colour variability in Basque boys aged 8-19 years. AB - Skin colour variation with increasing age was analysed using a cross-sectional sample of 796 Basque boys aged from 8 to 19 years. Measurements were taken at the upper inner arm and forehead by means of an EEL DS29 Digital Unigalvo reflectance spectrophotometer with a nine-filter head. Ontogenic changes of skin pigmentation were found to be statistically significant. The influence of the month in which measurements were taken on reflectance values has been studied. Comparisons with another similar study (Pembrokeshire, Wales population) were carried out. PMID- 8489203 TI - Acute motor axonal neuropathy: a frequent cause of acute flaccid paralysis in China. AB - In northern China, annual epidemics of acute-onset flaccid paralysis diagnosed clinically as Guillain-Barre syndrome have been recognized for at least 20 years. On the basis of an historical analysis of more than 3,200 patients, distinctive features include most cases occurring during the summer months among children and young adults, most of whom reside in rural areas. Of 90 patients with acute flaccid paralysis, 88 had a distinctive pattern that shares clinical and cerebrospinal fluid findings with demyelinating Guillain-Barre syndrome, but that differs from Guillain-Barre syndrome physiologically and pathologically. The clinical course is marked by rapidly progressive ascending tetraparesis, often with respiratory failure, but without fever, systemic illness, or sensory involvement. Cerebrospinal fluid is acellular, and elevations of protein content occur in the second or third week of illness. Electrodiagnostic studies show normal motor distal latencies and limb conduction velocities, but reduced compound muscle action potential amplitudes. Sensory nerve action potentials and, when elicitable, F waves are within the range of normal. Recovery is usually good. Autopsy studies have shown Wallerian-like degeneration of motor fibers. These studies establish that this is a distinctive syndrome, distinguishable from poliomyelitis and demyelinating Guillain-Barre syndrome. PMID- 8489204 TI - Zidovudine treatment of the AIDS dementia complex: results of a placebo controlled trial. AIDS Clinical Trials Group. AB - The efficacy of two doses of zidovudine was examined for the treatment of the acquired immunodeficiency syndrome (AIDS) dementia complex in a randomized, double-blinded, placebo-controlled trial conducted at nine study centers. For the initial 16 weeks, 40 subjects with mild to moderate AIDS dementia complex were randomized to one of three treatment arms: 400 mg of zidovudine five times daily, 200 mg of zidovudine five times daily, or placebo five times daily. After week 16, patients initially randomized to the placebo group were rerandomized to one of the two zidovudine treatment arms. The primary efficacy end point was improvement in performance on a battery of seven neuropsychological tests; the secondary end point was improvement on a protocol neurological evaluation directed at the cardinal features of the AIDS dementia complex. For the initial 16-week period, average z scores based on the neuropsychological test battery revealed a significant improvement in the combined treatment groups compared to the placebo group; however, when the two treatment groups were compared separately to the placebo group, only the group receiving the higher zidovudine dose exhibited significant improvement. After rerandomization of the placebo patients to one of the two treatment arms at week 16, this group also showed significant improvement in the average neuropsychological z score by week 32. These results extend previous observations that indicate a therapeutic benefit of zidovudine for the treatment of AIDS dementia complex. PMID- 8489205 TI - A controlled trial of lazabemide (RO19-6327) in untreated Parkinson's disease. Parkinson Study Group. AB - The monoamine oxidase type B inhibitor deprenyl (selegiline) has been demonstrated to delay the emergence of disability in early untreated Parkinson's disease. Lazabemide (RO19-6327) is a short-acting, reversible, highly selective inhibitor of monoamine oxidase type B which, unlike deprenyl, is not metabolized to active compounds. We conducted a randomized, double-blinded clinical trial to assess the short-term tolerability of lazabemide in subjects who had early, untreated Parkinson's disease. Two hundred and one patients were enrolled at 14 centers and randomized to receive 100 mg/day, 200 mg/day, or 400 mg/day of lazabemide or matching placebo. Subjects were followed for 8 weeks including a randomized, double-blinded withdrawal of lazabemide for 2 or 4 weeks. The primary measure of tolerability was the proportion of treated subjects who were able to complete the study on their originally assigned treatment. Clinical features were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). Lazabemide treatment was as well tolerated as placebo and was not attended by serious adverse experiences. A significant improvement in the activities of daily living component of the rating scale was found after 4 weeks of lazabemide treatment, although other subscale scores did not change significantly. The overall safety and benefits of lazabemide observed in this short-term study justify further long term investigations to determine if this monoamine oxidase type B inhibitor can slow the clinical progression of Parkinson's disease. PMID- 8489206 TI - Loss of C1 and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson's disease. AB - We used immunohistochemical analysis to determine whether medulla oblongata neurons containing phenylethanolamine N-methyltransferase (PNMT) are affected in patients who died with idiopathic Parkinson's disease (n = 7) compared with age matched control subjects who died with nonneurological diseases (n = 8). Transverse sections (50 microns) of medulla were prepared either for conventional neuropathological examination or for the immunohistochemical demonstration of PNMT. Immunopositive neurons at approximately 30 rostrocaudal levels, evenly spaced throughout the whole medulla, were mapped and cells in each section were counted with a camera lucida system linked to a computer. In the ventrolateral medulla, from the level of the obex to 11 mm rostral to the obex where the C1 group of neurons is located, there were 7,631 +/- 844 PNMT-positive neurons in control brains and 3,604 +/- 1,051 in brains affected by Parkinson's disease (47% of control). Many PNMT-positive neurons contained Lewy bodies. We observed a previously undescribed midline (C3) group of PNMT-positive neurons in normal brains, and this group was also severely affected (12% of control) in parkinsonian brains. Neither the C2 group nor the small PNMT-positive neurons in the nucleus tractus solitarii were significantly reduced in numbers but there was a reduction in the numbers of melanin-pigmented cells in both the ventrolateral (50% of control) and the dorsomedial (79% of control) region. Our results demonstrate a selective loss of C1 and C3 PNMT-positive neurons, providing the first quantitative evidence for damage to these presumed brainstem sympathetic premotor neurons in Parkinson's disease. These changes may underlie some of the autonomic symptoms occurring in this condition. PMID- 8489207 TI - Association of a monoamine oxidase B allele with Parkinson's disease. AB - Monoamine oxidase B (MAO-B) is implicated in the cause of Parkinson's disease (PD) because of its role in metabolizing the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, and forming H2O2 during dopamine metabolism. Altered MAO-B activity has been observed in PD platelets. Polymerase chain reaction was used to amplify a portion of the MAO-B gene. Polymerase chain reaction products were screened with restriction enzymes to identify fragments useful for single stranded conformational polymorphism analysis. A single-stranded conformational polymorphism was identified in an MAO-B polymerase chain reaction product after Hae III digestion. One hundred twenty-one control individuals were allelotyped with frequencies of 0.45 and 0.55 for alleles 1 and 2, respectively. Frequencies of 0.62 and 0.38 (1 and 2, respectively) were observed in a population of 46 patients with PD. The presence of MAO-B allele 1 is associated with a relative risk for PD of 2.03-fold (confidence interval, 1.44-2.61; p < 0.02). For comparison, a monoamine oxidase A polymorphism was used to determine allelic frequencies in these same populations and no statistically significant differences were found. These results suggest that an inherited variant of MAO-B may be involved in a genetic predisposition for PD. PMID- 8489208 TI - Analysis of autoantibody binding to 52-kd paraneoplastic cerebellar degeneration associated antigen expressed in recombinant proteins. AB - A 52-kd neural antigen was reported to be recognized by anti-Purkinje cell antibodies in serum of a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. In this study, we demonstrate that this neural antigen is recognized by antibodies known as anti-Purkinje cell antibody type I (PCAb Type I) and anti-YO. The latter's antigen is reported to be specific for the 62- to 64-kd antigen CDR62. Assuming that the 52-kd and 62- to 64-kd antigens share a common epitope(s) recognized by all of these antibodies, we examined the antigenic region on the 52-kd protein by immunoblots with deletion fragment proteins of the recombinant 52-kd protein. A major epitope was localized in the region of amino acid residues 94 to 133 of the 52-kd protein, which is the site of a leucine zipper motif. The potential pathogenicity of PCAb Type I is discussed. PMID- 8489209 TI - Persistent vegetative state: report of the American Neurological Association Committee on Ethical Affairs. ANA Committee on Ethical Affairs. PMID- 8489210 TI - Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis. AB - An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I--associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I- associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were detected in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of this virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder. PMID- 8489211 TI - Maple syrup urine disease: metabolic decompensation monitored by proton magnetic resonance imaging and spectroscopy. AB - Metabolic decompensation of maple syrup urine disease in a 3.5-year-old boy was monitored by means of proton magnetic resonance imaging and spectroscopy. In the acute stage, imaging showed diffuse cerebral edema. Proton spectra showed an elevation of lactate and a previously unassigned resonance at 1 ppm. This peak disappeared with normalization of branched-chain amino acids and oxoacids in the plasma and cerebrospinal fluid. In vitro spectroscopy of these metabolites at 1.5 T confirmed the chemical shift position of their methyl resonances at 1 ppm. The duration of lactate elevation correlated with the presence of brain edema and coma. These results demonstrate that magnetic resonance imaging can monitor therapeutic effects, and suggest that proton spectroscopy can detect cerebral accumulation of branched-chain amino acids and oxoacids in maple syrup urine disease. PMID- 8489212 TI - Callosal apraxia without agraphia. AB - We describe a patient with left unilateral ideomotor apraxia without left-sided agraphia caused by a callosal lesion that was demonstrated by magnetic resonance imaging. The clinical features, together with data in the literature, suggest that the callosal fibers for writing are concentrated in the posterior corpus callosum, while those for praxis cross in the more rostral part of the posterior half of the callosum. PMID- 8489213 TI - Spastic ataxia associated with human T-cell lymphotropic virus type II infection. AB - Human T-cell lymphotropic virus type one (HTLV-1) is associated with tropical spastic paraparesis or HTLV-I--associated myelopathy. We report 2 women with a spastic ataxic illness similar to HTLV-I--associated myelopathy infected solely with HTLV-II. Identification of HTLV-II infection was made serologically, by polymerase chain reaction, and by viral culture (in 1 woman). One woman, treated with 200 mg of danazol orally, three times daily, had pronounced improvement in ambulation, nocturnal spasticity, and nighttime urinary frequency. It appears that infection with HTLV-II may cause an illness similar to HTLV-I--associated myelopathy, but distinguished by the presence of ataxia. PMID- 8489214 TI - Nonepileptic seizures during apparent sleep. AB - We report 12 patients with nonepileptic seizures (NESs) documented with video electroencephalographic monitoring during apparent sleep. There were 7 females and 5 males, ages 11 to 67 years (mean, 33 yr). In all patients there was a well organized posterior alpha rhythm present immediately before onset of clinical changes despite the appearance of sleep. Patients later "confirmed" that these attacks occurred during sleep. Features of these episodes were typical of NESs and none were associated with ictal or postictal electroencephalographic changes other than muscle and movement artifact. Provocative testing with suggestion confirmed the nonepileptic nature of these episodes in 9 patients. Three patients had epileptiform discharges during prolonged interictal recordings and 1 had a documented complex partial seizure. Our findings indicate that reports of seizures during sleep are not uncommon among patients with NESs. PMID- 8489215 TI - Oscillopsia and horizontal nystagmus with accelerating slow phases following lumbar puncture in the Arnold-Chiari malformation. AB - Oscillopsia and nystagmus began in a woman 2 weeks after an inadvertent lumbar puncture during anesthesia for childbirth. Examination showed horizontal torsional jerk nystagmus in all positions of gaze. Magnetic-search-coil oculography revealed accelerating slow phases, with an increase in nystagmus amplitude in darkness. Magnetic resonance images showed type 1 Arnold-Chiari malformation. Three months after occipital decompressive surgery, nystagmus had almost disappeared. Accelerating slow phases should not be considered diagnostic of congenital nystagmus, especially with an onset of oscillopsia in adult life; imaging should be considered to exclude treatable hindbrain anomalies. Lumbar puncture in patients with the Arnold-Chiari malformation may accentuate craniospinal pressure dissociation and precipitate neurological signs. PMID- 8489216 TI - Reactive nitrogen intermediates: effector molecules of immune-mediated inflammatory nervous system disorders? PMID- 8489217 TI - New neuroimaging methods and the neurological examination. PMID- 8489218 TI - Skilled perioperative care is not enough--customer service is a must. PMID- 8489219 TI - Bloodborne pathogens. PMID- 8489220 TI - Perioperative nursing care quality. Patients' opinions. PMID- 8489221 TI - Children's drawings. A preoperative assessment tool. PMID- 8489222 TI - Anxiety of elective surgical patients' family members. Relationship between anxiety levels, family characteristics. AB - Technological advances in the OR create new practices and procedures; however, humanistic and holistic approaches to nursing care remain the foundation of clinical practice. Perioperative nurses recognize that family members experience anxiety during surgery, especially during the time the patient is in the OR. Ironically, it is during this time period that little or no meaningful communication occurs between family members and health professionals. Patients continue to be discharged sooner, and in sicker condition, to be cared for by their family members. Families require information about how to provide postoperative care. Anxiety levels need to be decreased sufficiently to allow family members to use the information they are taught and ask appropriate questions. Interventions that reduce family members' anxiety need to be developed and tested so that family members can help patients after surgery. Using research findings as a basis for perioperative nursing practice may mean changing traditions and attitudes about family members of surgical patients. In the consumer-oriented climate of current health care, doing the "new" may make a difference in the market share. This "new" may be independent nursing interventions designed to reduce family members' anxiety during the intraoperative waiting period. PMID- 8489223 TI - Perioperative nurse caring behaviors. Perceptions of surgical patients. PMID- 8489224 TI - Ambulatory surgery--hospital-based vs freestanding. A comparative study of patient satisfaction. PMID- 8489225 TI - Reoperative cardiac surgery. Challenges, perioperative nursing considerations. PMID- 8489226 TI - Comprehensive perioperative care: patient assessment, teaching, documentation. PMID- 8489227 TI - Patients deserve respectful surgical environment. PMID- 8489228 TI - New American Nurses Association lobbyist thrives on involvement in his native Washington, DC. Interview by Celeste Goldbaum. PMID- 8489229 TI - The assumed assimilation of cholesterol by Lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. AB - To study the mechanism of the propsed assimilation of cholesterol, we cultured various strains of Lactobacillus acidophilus and a Bifidobacterium sp. in the presence of cholesterol and oxgall. During culturing, both cholesterol and bile salts were precipitated. Because of bacterial bile salt deconjugation, no conjugated bile salts were observed in either the culture fluids or the pellets. During incubation, the cell count and optical density decreased. The degree of precipitation of bile salts and of cholesterol was dependent on the culture conditions. If L. acidophilus RP32 was cultured under acidifying conditions, the degree of precipitation of deconjugated bile salts was higher than if the pH was maintained at 6.0. Under acidifying conditions, cholesterol was coprecipitated with the bile salts, whereas in pH-controlled cultures, no coprecipitation of cholesterol was observed. From control experiments with different mixtures of bile salts, it appeared that coprecipitation of cholesterol during culturing was a result of formation of deconjugated bile salts, which have a decreased solubility at pH values lower than 6.0. It is concluded that the removal of cholesterol from the culture medium by L. acidophilus RP32 and other species is not due to bacterial uptake of cholesterol, but results from bacterial bile salt deconjugating activity. PMID- 8489230 TI - Mycoplasmalike organisms (MLOs) and distinguish them from other MLOs. AB - DNA of 10 lines of rice yellow dwarf (RYD) mycoplasmalike organisms (MLOs) from Japan, the Phillippines, and Thailand hybridized with four probes containing chromosomal and six probes containing extrachromosomal DNA of a Tochigi (Japan) line of RYD MLO. One chromosomal probe (RYD9) and all six extrachromosomal probes hybridized with various other MLOs (sugarcane white leaf, onion yellows, cineraria witches'-broom, Japanese hornwort witches'-broom, water dropwort wiches'-broom, gentian witches'-broom, udo dwarf, tsuwabuki witches'-broom, pelargonium witches's-broom, peach western-X, and pear decline). DNA from the culturable mollicutes Spiroplasma kunkelii, Spiroplasma citri, Mycoplasma hominis, and Mycoplasma orale did not hybridize with RYD MLO probes. The extrachromosomal DNAs hybridizing with the probes showed variations in electrophoretic behavior. PMID- 8489231 TI - Impact of the ring-billed gull (Larus delawarensis) on the microbiological quality of recreational water. AB - We evaluated the impact of the ring-billed gull (Larus delawarensis) on the microbiological quality of water. We measured fecal coliforms, Salmonella spp., and Aeromonas spp. in the gull droppings and the number of fecal coliforms in the water prior to and after attracting these birds to the beach with food. Gulls can contribute to the bacteriological degradation of recreational water. PMID- 8489232 TI - Use of autoradiography to assess viability of Helicobacter pylori in water. AB - Autoradiographic methods have been developed to detect metabolic activity of viable but nonculturable cells of Helicobacter pylori in water. Four strains of H. pylori were studied by using microcosms containing suspensions of 72-h cultures in water. The suspensions of aged, nonculturable cells of H. pylori were incubated with [3H]thymidine for 24 to 72 h, after which the cell suspensions were exposed to Kodak NTB2 emulsion for 3 to 28 days. Each sample was processed with three separate controls to rule out false-positive reactions. The organism remains viable and culturable under these conditions for up to 48 h and, in some cases, 20 to 30 days, depending on physical conditions of the environment. We found that temperature was a significant (P < or equal to 0.01) environmental factor associated with the viability of H. pylori cells in water. Autoradiographs of tritium-labeled cells of H. pylori revealed aggregations of silver grains associated with uptake by H. pylori of radiolabelled substrate. Findings based on the autoradiographic approach give strong evidence supporting the hypothesis that there is a waterborne route of infection for H. pylori. The possibility that H. pylori may persist in water in a metabolically active stage but not actively growing and dividing is intriguing and relevant to public health concerns. PMID- 8489233 TI - A proposed nonpathogenic biological indicator for thermal inactivation of Listeria monocytogenes. AB - Listeria innocua M1 was developed as a thermal processing indicator organism for L. monocytogenes by selection of a rifampin- and streptomycin-resistant mutant. zetaD values were 5.6 and 5.8 degrees C, and D (68 degrees C) values were 3.8 and 4.9 s for L. monocytogenes and L. innocua, respectively, in skim milk. The advantages of easy selection, similar heat resistance, and nonpathogenicity make L. innocua M1 appropriate for challenge studies designed to evaluate process lethality with respect to L. monocytogenes. PMID- 8489234 TI - Inhibitory effect of oolong tea polyphenols on glycosyltransferases of mutans Streptococci. AB - Oolong tea extract (OTE) was found to inhibit the water-insoluble glucan synthesizing enzyme, glucosyltransferase I (GTase-I), of Streptococcus sobrinus 6715. The GTase-inhibitory substance in the OTE was purified successive adsorption chromatography on Diaion HP-21 and HP-20 columns; this was followed by further purification by Sephadex LH-20 column chromatography. A major fraction that inhibited GTase activity (fraction OTF10) was obtained, and the chemical analysis of OTF10 indicated that it was a novel polymeric polyphenol compound that had a molecular weight of approximately 2,000 and differed from other tea polyphenols. Catechins and all other low-molecular-weight polyphenols except theaflavin derived from balck tea did not show significant GTase-inhibitory activities. It was found that OTE amd PTF10 markedly inhibit GTase-I and yeast alpha-glucosidase, but not salivary alpha-amylase. Various GTases purified from S. sobrinus and Streptococcus mutans were examined for inhibition by OTE and OTF10. It was determined that S. sobrinus GTase-I and S. mutans cell-free GTase synthesizing water-soluble glucan were most susceptible to the inhibitory action of OTF10, while S. sobrinus GTase-Sa and S. mutans cell-associated GTase were moderately inhibited; no inhibition of S. sobrinus GTase-Sb was observed. Inhibition of a specific GTase or specific GTases of mutants streptococci resulted in decreased adherence of the growing cells of these organisms. The inhibitory effect of OTF10 on cellular adherence was significantly stronger than that of OTE. PMID- 8489235 TI - The carnitine acyltransferases and their role in modulating acyl-CoA pools. AB - The role of carnitine via the action of carnitine acyltransferase in buffering CoA availability in the mitochondrial matrix is well known. There is now sufficient evidence to extend this to a general role. Carnitine can buffer the acylation state of the CoA pool for any type of acyl group that is a substrate for the carnitine acyltransferase family of enzymes. Specific carnitine acyltransferases in each organelle or membrane can modulate the reserves of free CoA and acyl-CoA in ways specific to the local metabolic demands. The use of inhibitors of carnitine acyltransferases in complex systems and in vivo now permits exploration of the consequences of this role. PMID- 8489236 TI - Characterization of superoxide dismutase-insensitive cytochrome c reductase activity in HL-60 cytosol as NADPH-cytochrome P450 reductase. AB - A flavoprotein dehydrogenase assayed for the activity of electron transfer from NADPH to cytochrome c was highly purified from the cytosolic fraction of differentiated human promyelocytic leukemia HL-60 cells. The purified enzyme had an apparent molecular mass of 68 kDa by sodium dodecyl sulfate gel electrophoresis and an equimolar amounts of flavin mononucleotide and flavin adenine dinucleotide. The purification factor of the enzyme with respect to the cytosolic fraction was close to 1100 and the recovery of activity was approximately 18%. Reduction of cytochrome c by NADPH indicated Michaelis-Menten kinetics with a Km value of 1.50 microM for NADPH. When cytochrome c was the varied substrate, a Km value of 4.10 microM was obtained. NADH was not an effective electron donor for cytochrome c reduction and NADPH-dependent reduction of nitroblue tetrazolium was negligibly small. The purified enzyme alone did not exhibit superoxide production, and NADPH oxidase activity was not markedly stimulated upon incubation of the reductase with cytochrome b558 purified from porcine neutrophils. The purified flavoprotein gave a positive cross-reactivity to polyclonal antibodies raised to microsomal NADPH-cytochrome P450 reductase, indicating structural homology between these enzymes. The catalytic properties of the purified NADPH-cytochrome c reductase have similarities to those of liver NADPH-cytochrome P450 reductase. PMID- 8489237 TI - Effects of heparin and other glycosaminoglycans on elastin production by cultured neonatal rat lung fibroblasts. AB - Proteoglycans are important structural elements of the extracellular matrix, and may contribute to the dynamic architecture of the lung and also influence pulmonary gas and solute exchange. The potential for proteoglycans and glycosaminoglycans to modulate the synthesis and deposition of elastin, another important extracellular matrix component of the lung, has not been established. Therefore the effects of glycosaminoglycans on the steady-state level of elastin mRNA, the incorporation of [3H]valine into tropoelastin, the distribution of soluble elastin in the medium and cell layer, and insoluble elastin deposition have been examined using cultured neonatal rat lung fibroblasts. Heparin decreases the soluble elastin content of the culture medium while increasing the soluble elastin content of the cell layer. This altered partitioning of soluble elastin is associated with an increase in steady-state elastin mRNA and an increase in the deposition of insoluble elastin in the extracellular matrix. Some of these effects may result from the binding of heparin to soluble elastin at physiological concentrations of NaCl. The galactosamine-containing glycosaminoglycans, chondroitin sulfate and dermatan sulfate, differ from heparin in that they increase the quantity of soluble elastin in the culture medium and decrease the deposition of insoluble elastin in the extracellular matrix. Proteoglycans, which are present in most elastic tissues, may participate in the regulation of elastin synthesis and deposition during periods of new elastin formation. PMID- 8489239 TI - Transcriptional activation of cytochrome P450 2B1/2 genes in rat liver by diallyl sulfide, a compound derived from garlic. AB - Previous work in our laboratory demonstrated that cytochrome P450 2B1 in rat liver was induced, but P450 2E1 was inhibited and inactivated, by diallyl sulfide (DAS), a compound derived from garlic. Such a selective effect on P450 enzymes is of considerable interest toward the understanding of dietary effects on xenobiotic metabolism. In the present study, the mechanism of P450 2B1 induction by DAS was investigated. Following a single dose of DAS (200 mg/kg body weight, ig), liver microsomal pentoxyresorufin dealkylase (PORd) activity, a representative activity of P450 2B1, was induced 3-, 16-, 26-, and 43-fold at 6, 12, 18, and 24 h after the treatment, respectively. A corresponding increase in the level of P450 2B1/2 protein was observed by immunoblot analysis. The level of P450 2B1/2 mRNA in rat liver also increased markedly, reaching a maximum at 12 h after the DAS treatment. Hybridization with the isozyme-specific oligonucleotide probes revealed that the mRNA levels of both P450s 2B1 and 2B2 were induced. In contrast, the level of P450 2E1 mRNA in the liver of DAS-treated rats was not changed. The results of nuclear run-on assay revealed that the transcriptional rate of P450 2B1/2 genes in the rat liver increased 13-fold at 6 h after DAS administration and returned to the control value at 24 h. The transcription of P450 2B1/2 genes was blocked completely by alpha-amanitin, an inhibitor of RNA polymerase II. These results clearly demonstrate that the induction of P450 2B1/2 in rat liver by DAS is mainly due to transcriptional activation. In the DAS treated rats, P450 2B1/2 mRNA was also markedly induced in the stomach and duodenum. The maximal induction was found at 12 h after the treatment while the levels of P450 2B1/2 mRNA increased 66-fold in the duodenum and 23-fold in the stomach. DAS treatment, however, did not change the levels of P450 2B1/2 mRNA in the lung and nasal mucosa. PMID- 8489238 TI - Induction of flavin-containing monooxygenase (FMO B) in rabbit lung and kidney by sex steroids and glucocorticoids. AB - Modulation of lung and kidney levels of flavin-containing monooxygenase (FMO) isoform B following sc administration of dexamethasone, progesterone, beta estradiol, aldosterone, or beta-estradiol plus progesterone was examined in male rabbits. Both dexamethasone and progesterone increased FMO B protein levels in lung. N-Oxygenation of N,N'-dimethylaniline (DMA) was significantly induced in lung microsomes from rabbits treated with progesterone. In kidney, only dexamethasone was effective in inducing FMO B protein levels and DMA N oxygenation. Surgical implantation of osmotic pumps containing beta-estradiol or progesterone into non-pregnant female rabbits resulted in elevated plasma levels of these steroids after 4-5 days at which point the lung levels of FMO B were induced by 35 and 82% for beta-estradiol and progesterone, respectively. The responsiveness of FMO B in lung to both progesterone and glucocorticoids and in kidney to only the latter is consistent with the developmental pattern of both maternal FMO B and peak plasma levels of these steroids during pregnancy. PMID- 8489240 TI - Purification and characterization of salicylhydroxamic acid reductase from rat liver. AB - Salicylhydroxamic acid reductase, which catalyzes the reduction of salicylhydroxamic acid to salicylamide, was purified from rat liver cytosol. The purification procedure consisted of fractionation with ammonium sulfate, chromatography with Phenyl-Toyopearl 650, DEAE-cellulose, hydroxyapatite, and Sephadex G-200, and chromatofocusing with PBE94. The molecular weight of the enzyme was estimated to be about 140,000 by Sephadex G-200 gel filtration and 152,000 by polyacrylamide gel electrophoresis. The enzyme was dissociated into two different subunits with estimated molecular weights of 41,000 and 32,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These facts suggested that the enzyme is a heterotetramer consisting of two pairs of two nonidentical polypeptide chains. The Km value of the enzyme for salicylhydroxamic acid was estimated to be 91.5 or 88.7 microM in the presence of NADH or NADPH, respectively. The isoelectric point of the enzyme is pH 5.4. The enzyme was highly specific for salicylhydroxamic acid, but it also showed some activity with other hydroxamic acids such as nicotinohydroxamic acid and N hydroxy-2-acetylaminofluorene. The enzyme activity was inhibited by allopurinol, oxipurinol, dicumarol, menadione, p-chloromercuribenzoic acid, sodium arsenite, potassium cyanide, cupric sulfate, and disulfiram, but little inhibition was observed with oxygen. PMID- 8489241 TI - Synthesis and turnover of ceruloplasmin in rats treated with 17 beta-estradiol. AB - The effects of estrogen on synthesis and turnover of ceruloplasmin were studied in adult female Fischer rats. Daily treatment with 140 microgram 17 beta estradiol resulted in a slow rise of ceruloplasmin concentrations, as measured by p-phenylenediamine oxidase activity, leading to a 70% increase by 7 days and a tripling by Day 14. Ceruloplasmin protein concentrations increased to the same degree, based on yields of the protein obtained during purification. Effects of estrogen on rates of synthesis (incorporation of [3H]leucine) were followed, using immunoprecipitation of total ceruloplasmin or isolation of its two major isoforms (Rfs 0.4 and 0.6 in native gel electrophoresis). Synthesis was increased by 7 days and was 2.5 times that of controls by Day 14. Both forms of ceruloplasmin showed the same specific activities and degree of increase in rate of synthesis. Rates of ceruloplasmin turnover were unaffected, based on double labeling with 3H- and 14C-leucine, but were three- to fourfold faster than for total plasma protein. The enzymatically more active 0.6 Rf form of ceruloplasmin had a faster turnover rate than the 0.4 Rf form. Estrogen treatment doubled ceruloplasmin mRNA levels by 7 days and almost tripled them by Day 14. Most of the ceruloplasmin mRNA was associated with the endoplasmic reticulum-bound polyribosomes. We conclude that estrogen increases the rate of synthesis of two forms of ceruloplasmin by indirectly increasing liver concentrations of its mRNA but has no effect on ceruloplasmin turnover. PMID- 8489242 TI - Isolation of a phospholipid inhibitor of platelet activating factor-induced activity from perfused rat liver: identification as phosphatidylglycerol. AB - An endogenous inhibitor of platelet activating factor action was isolated from perfused rat liver. It was purified by thin-layer chromatography and high performance liquid chromatography and subjected to chemical modifications in order to identify its structure. On the basis of its fast atom bombardment-mass spectrum it was characterized as phosphatidylglycerol composed mainly of 16:0/18:1 and 16:0/20:2 fatty acyl chains ([M+H]+ at m/z 749 and 775, respectively) and very minor levels of 18:0/18:1 and 18:0/20:2. The purified compound exhibited inhibition on rabbit platelet aggregation induced by 5 x 10( 10) M platelet activating factor (PAF) at an EC50 value near 2.5 x 10(-6) M and on the serotonin secretion at an EC50 7 x 10(-6) M. Other phospholipids isolated from the liver preparations, such as phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cardiolipin (diphosphatidylglycerol), and phosphatidic acid, exhibited no inhibitory activity in the concentration range from 1 x 10(-4) to 1 x 10(-7) M nor did they induce any aggregation, or lysis, of the platelets. Of importance, phosphatidylglycerol could inhibit thrombin- and ADP-induced aggregation of rabbit platelets. These results suggested a possible site of inhibition common to the signal transduction pathway of these agonists. Preliminary binding experiments showed a noncompetitive type of inhibition on PAF binding to intact rabbit platelets. PMID- 8489243 TI - Archaebacterial adenylate kinase from the thermoacidophile Sulfolobus acidocaldarius: purification, characterization, and partial sequence. AB - For the first time an adenylate kinase of archaebacterial origin has been purified to homogeneity. The enzyme from the extreme thermoacidophile Sulfolobus acidocaldarius (DSM 639) has been found to consist of a 23- to 24-kDa polypeptide likely to form a dimer under in vitro conditions. Its temperature optimum is about 90 degrees C; the pH optimum is 5.3-6.0, depending on the observed direction of the reaction. The KM values for ATP, AMP, and ADP are almost equal (0.6-0.7 mM). The enzyme is absolutely specific for AMP as phosphate acceptor but has a broad specificity for nucleotide triphosphates as donors. It requires divalent metals for activity with Mg2+ > Mn2+ > Ca2+ > Zn2+ in the order of decreasing potency. Distinct from mammalian enzymes the sensitivity toward the typical inhibitor diadenosine-5,5'-pentaphosphate is extremely low; > 300 microM is required for 50% inhibition, suggesting an altered distance between the AMP /ATP-binding sites. The thermostability of the protein decreases sharply at room temperatures above 90 degrees C. It exhibits unusual stability, however, toward acidic pH. A 41-residue N-terminal sequence has been determined which allowed us to construct probes for the genetic approach. From residue 8-15 the protein contains the typical glycine rich P-loop as well as another conserved sequence stretch 21 residues further. Isolation of the gene is in progress. PMID- 8489244 TI - Domains of rat heme oxygenase-2: the amino terminus and histidine 151 are required for heme oxidation. AB - Cleavage of heme b (Fe-protoporphyrin IX) at the alpha-meso carbon bridge is catalyzed by heme oxygenase isozymes, HO-1 and HO-2, to form biliverdin IX alpha. Currently, we have examined the requirement for the amino terminus and the hydrophobic carboxy terminus of rat HO-2 expressed in Escherichia coli for heme degradation activity and have assessed the importance of His 151 for this activity. His 151 is in the longest span of amino acids (24 residues) which are present, with only a single conservative substitution, in seven cloned heme oxygenases including the apparent single isozyme in chicken. We show His 151 is essential for cleavage of heme, as substitution of alanine for this residue by site-directed mutagenesis resulted in expression of an inactive protein with immunoreactivity toward antibody to rat HO-2. A cDNA construct in which nucleotides encoding the 33 N-terminal amino acid residues were deleted, when expressed, produced a protein of predicted size and immunoreactivity with antibody to HO-2 but also devoid of heme degrading activity. The presence of additional residues at this terminus, for the most part, accounts for the larger size of HO-2 compared to HO-1. Conversely, the hydrophobic region at the carboxy terminus did not appear to be essential for heme degradation. A construct in which the sequence encoding the primarily hydrophobic amino acids of the carboxy terminus was replaced by a sequence encoding predominantly hydrophilic residues expressed a protein which retained full capability to convert heme to biliverdin. Further, the construct with a hydrophilic carboxy terminus was not appreciably associated with bacterial membranes, suggesting that the carboxy terminus in the wild-type protein serves as a membrane anchor for this enzyme. PMID- 8489245 TI - Possible roles of the 3'-flanking sequences of the human activin beta A subunit gene in its expression. AB - Tumor promoter 12-O-tetradecanoylphorbol-13-acetate stimulates an increase in erythroid differentiation activity in human fibrosarcoma HT1080 cells. Here, we demonstrate that this process involves a rapid accumulation of five species of activin beta A/erythroid differentiation factor mRNA, followed by protein kinase C activation, and that variation in size of the activin transcripts is due to multiple 3' ends, presumably reflecting an alternative polyadenylation. In transiently transfected HT1080 cells, a 97-bp DNA fragment containing an AP-1 consensus sequence (TGAGTCA) located in the 3'-flanking region of the activin gene was capable of activating the heterologous herpes simplex virus thymidine kinase (tk) and SV40 early promoters, and a cotransfected c-Jun enhanced these fusion promoter activities. The deletion of TGAG sequences from the AP-1 element in the 97-bp DNA sequence context abolished its c-Jun-mediated activation from the tk promoter even in HT1080 cells overexpressing stably transfected c-Jun. Cotransfected adenovirus E1A products repressed the tk promoter activity enhanced by the activin AP-1 element itself or in concert with transiently transfected c Jun, indicating that the putative AP-1 sequence acts as an activator element, depending upon c-Jun activity. These results suggest that the 3'-flanking DNA sequences of the human activin beta A subunit gene play an important role in its expression. PMID- 8489246 TI - Crystallization and preliminary X-ray crystallographic analysis of carboxylesterase from pseudomonas fluorescens. AB - Large crystals of carboxylesterase from Pseudomonas fluorescens have been grown in the presence of dioxane using ammonium sulfate and lithium sulfate as precipitant. They belong to the tetragonal space group P4(1)2(1)2 (or P4(3)2(1)2), with unit cell dimensions of a = 82.01 (+/-0.06) A and c = 145.44 (+/- 0.08) A. The presence of one carboxylesterase dimer in the asymmetric unit gives the crystal volume per protein mass (VM) of 2.56 A3/Da and solvent fraction of 52.0% by volume. The crystals diffract to at least 2.3 A Bragg spacing when exposed to CuK alpha X rays from a rotating anode generator. X-ray data (nearly complete to 2.6 A Bragg spacing) have been collected from a native crystal. PMID- 8489247 TI - Serum protein of 135-kDa molecular weight--a molecular signal for cardiac hypertrophy. AB - A serum protein, similar to the 135-kDa protein which appears during experimentally induced cardiac hypertrophy in rats, was identified in human serum by Western blot analysis using anti-rat 135-kDa protein antibody. The rat protein antibody gave a very strong positive signal when reacted with sera obtained from cardiac patients, suggesting an induced level of this protein in patients' sera when compared to normal sera from healthy individuals. Multiple injections of polyclonal anti-rat 135-kDa protein antibody to aorta-constricted animals completely inhibited the development of cardiac hypertrophy, suggesting that this protein could be hypertrophy specific. This was further substantiated by the decrease in the expression of a molecular marker such as the beta myosin heavy chain gene in aorta-constricted but antibody-injected animals. Further, the presence of high levels of this protein in first- and third-day neonatal animals is also suggestive of the hypertrophy-specific nature of this protein as the heart is subjected to high pressure overload immediately after birth. PMID- 8489248 TI - Proteoglycan metabolism is age related and modulated by isoforms of platelet derived growth factor in bovine articular cartilage explant cultures. AB - The influence of recombinant human platelet-derived growth factor (PDGF) on proteoglycan metabolism was examined in bovine articular cartilage explants under serum-free conditions. All three isoforms of PDGF (AB, AA, and BB) dose dependently increased proteoglycan biosynthesis and decreased the rate of proteoglycan catabolism in cartilage explants obtained from young (1-6 weeks), adolescent (2-6 months), and adult animals (2-3 years). The biosynthetic stimulative effect of PDGF-AA was significantly lower than that of PDGF-AB only in adult tissues. The decrease in catabolic rate was more pronounced in younger animals. For culture periods of up to 12 days, the three PDGF isoforms did not have an effect on DNA synthesis. The molecular size of both the proteoglycan monomers and the glycosaminoglycan chains and the chondroitinase ABC sensitive pool decreased with age of the animal, but were not altered by PDGF-AB treatment. These data show that the three recombinant human PDGF isoforms contributed to matrix homeostasis in the articular cartilage explant system, with no apparent mitogenic effect. PMID- 8489249 TI - The human platelet dense granule: serotonin uptake, tetrabenazine binding, phospholipid and ganglioside profiles. AB - The functioning and composition of human platelet dense granules were studied using granules purified by Percoll fractionation. Reserpine-blockable serotonin (5-HT) uptake by the dense granule fraction was characterized and also demonstrated in the crude membrane fraction. Tetrabenazine (TBZ)-displaceable [3H]ketanserin binding was used to label the granular 5-HT transporter. Scatchard analyses, Hill plots, displacement curves, and binding kinetics indicated that TBZ-displaceable [3H]ketanserin binding labeled a site similar to that previously reported for chromaffin granules and synaptic vesicles. Analysis of phospholipid profiles in platelet fractions revealed that most platelet lysolecithin was associated with the dense granule fraction. Ganglioside analysis indicated that the predominant platelet ganglioside, GM3, was highly enriched in the dense granule fraction. The data lend further support to the idea that the 5-HT transporter complex is similar in platelet dense granules, chromaffin granules, and synaptic vesicles. However, the ganglioside and phospholipid findings clearly distinguish the types of storage sites and raise questions concerning the functional roles of dense granule GM3 and lysolecithin. PMID- 8489250 TI - Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor. AB - This report describes the post-translational modifications of recombinant human differentiation-stimulating factor, a 180-residue glycoprotein that is secreted from transfected Chinese hamster ovary cells. Peptide peptides containing six potential N-glycosylation sites were analyzed to determine that Asn residues 9, 34, 63, 73, 96, and 116 were utilized. Additional peptides, generated by tryptic digestion of peptic fragments, allowed the assignments of three intrachain disulfide bonds (Cys-18 to Cys-131, Cys-12 to Cys-134, and Cys-60 to Cys-163). PMID- 8489251 TI - Chronic effects of glucose on insulin signaling in A-10 vascular smooth muscle cells. AB - To examine the effects of hyperglycemia on insulin signaling in A-10 vascular smooth muscle cells, cells were treated with extracellular D-glucose and effects of insulin were studied on the diacylglycerol-protein kinase C signaling system. A-10 cells specifically bound 125I-insulin, and insulin-like growth factor-I did not displace the label. 125I-insulin binding was unaltered under hyperglycemic conditions. To determine if insulin receptors were coupled to other insulin regulated processes, diacylglycerol, protein kinase C, and glucose transport were evaluated. Insulin increased cellular diacylglycerol (DAG) levels which were also increased following glucose treatment and not further stimulated by insulin. The uptake of 2-[3H]deoxy-D-glucose (2-DOG) was stimulated by insulin and 12-O tetradecanoyl phorbol 13-acetate (TPA). Insulin- and TPA-stimulated 2-[3H]DOG uptake was inhibited by a protein kinase inhibitor, staurosporine. Preincubation of cells with 500 nM TPA overnight resulted in the inhibition of insulin- and TPA stimulated 2-[3H]DOG uptake. Protein kinase C activity was translocated from cytosolic to membrane fractions following insulin treatment. Overnight glucose (25 mM) treatment resulted in a 50% decrease in protein kinase C enzyme activity and > 90% decrease in protein kinase C beta immunoreactive levels. Protein kinase C activity and levels were not affected by osmotic control media containing mannitol. A-10 cells express GLUT4-type glucose transporters. Neither insulin regulatable glucose transporter (GLUT4) mRNA nor GLUT4 protein levels were diminished by glucose. Significant decreases in insulin- and TPA-stimulated 2 [3H]DOG uptake occurred, however, with glucose. The down-regulation of protein kinase C beta and resultant inhibition of 2-[3H]DOG uptake by chronic glucose suggests a biochemical link between hyperglycemia and DAG-protein kinase C signaling in vascular smooth muscle cells. PMID- 8489252 TI - Crystallization and preliminary X-ray analysis of subtilisin DY, a natural mutant of subtilisin Carlsberg. PMID- 8489253 TI - Spermidine-induced alteration in the gene-spacer discrimination of nucleases in protonated DNA. AB - The sequence preference of a Drosophila lysosomal DNase was studied on the Drosophila hsp 70 heat-shock and histone recombinants, which carry six different genes, and the surrounding spacer sequences. The distribution of cleavage sites was random in respect of the locations of gene and spacer sequences. However, in the presence of 10 mM spermidine, a major transition was observed: the coding sequences became more susceptible than the spacer regions to nuclease attack. A similar transition was induced in the sequence preference of DNase I if the digestion was performed in the presence of spermidine at pH 5.2. At pH 7.5, spermidine does not influence the sequence preference of DNase I, which indicates the involvement of DNA protonation in this transition. In the presence of spermidine, the distributions of preferred and protected sequences were almost indistinguishable for these nucleases, suggesting that the protonated DNA, and not the enzymes, is the target of spermidine. A Drosophila embryonal protein was detected and partially purified which induced the same transition as observed in the presence of spermidine. The purified protein preferentially protected the spacer DNA sequences against acid DNase or DNase I cleavage in the hsp 70 heat shock and histone gene recombinants. The protection was concentration dependent and occurred only at pH 5.2. The transition of nuclease specificity is probably due to a conformational change in the protonated DNA, induced by the binding of either the embryonal protein or spermidine. PMID- 8489254 TI - Mobility and molecular orientation of vitamin E in liposomal membranes as determined by 19F NMR and fluorescence polarization techniques. AB - To elucidate the molecular orientation and mobility of alpha-tocopherol (vitamin E) in membranes, 19F nuclear magnetic resonance (NMR) was applied. In bilayer phosphatidylcholine (PC) liposomes, 19F NMR spin-spin relaxation times (T2) of 19F-labeled methyl groups on either the chromanol moiety or the isoprenoid side chain of alpha-tocopherol were significantly decreased compared to those for alpha-tocopherol in solution (CDCl3), suggesting that the vitamin E molecule exists in the lipid core of membranes and that its motional freedom is significantly restricted. The difference in T2 values between the solution state and PC liposomes was greatest for the 5a-CF3 on the chromanol moiety compared with other methyl groups on the isoprenoid side chain. Hence, it is thought that the chromanol moiety of alpha-tocopherol may fit tightly near the surface of the membrane because of its hydrophilicity. When Pr3+ was added to the liposomal suspension, the intensity of the NMR signal for 5a-CF3 changed faster than those of the other methyl groups. When the surface of the liposomal membranes was positively charged using stearyl amine, the mobility of the 5a-methyl group, expressed as the correlation time (tau c), was quite similar to that in negatively charged membranes. These results indicate that the chromanol moiety of alpha-tocopherol may orient near the membrane surface, and that the hydroxyl group may be hydrogen bonded to the ester carbonyl of PC. For further confirmation of this conclusion, time-dependent changes in the fluidity of liposomes caused by the addition of Pr3+ were measured at the surface and inner region of liposomal membranes using a fluorescence polarization technique. The fluidity increased in the surface region and decreased in the inner region of liposomes containing alpha-tocopherol. These results show that when praseodymium ions may pass through the liposomal membrane, the hydrogen bonds between alpha tocopherol and the ester carbonyl of PC may be broken, leading to the formation of an alpha-tocopherol-Pr3+ complex, thus causing the fluidity to increase. Based on the findings obtained, mobility and molecular orientation of vitamin E in membranes are proposed. PMID- 8489255 TI - Beta 1-3-N-acetylglucosaminyltransferase in human leukocytes: properties and role in regulating neolacto glycosphingolipid biosynthesis. AB - There are well-established differences in the expression of neolacto neutral glycosphingolipids among human leukocyte subclasses. Mature myeloid cells express several types of these compounds, whereas mature lymphoid cells are deficient in such compounds. The biochemical basis for this is unknown. Therefore, enzyme studies were done to determine whether different classes of leukocytes (represented by cell lines) contained beta 1-3-N-acetylglucosaminyltransferase activity (EC 2.4.1.149, beta 1-3GlcNAcT(i)). This enzyme participates in the synthesis of Type 2 chains in glycosphingolipids by catalyzing the following two reactions: (i) Gal beta 1-4Glc beta 1-1Cer (lactosylceramide, LacCer) + UDP GlcNAc-->GlcNAc beta 1-3Gal beta 1-4Glc beta 1- 1Cer (lactotriaosylceramide) and (ii) Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer (neolactotetraosylceramide) + UDP-GlcNAc-->GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The first reaction may be the key step in the biosynthetic pathway of neolacto structures in human leukocytes. Therefore, extracts from several cell lines representative of both myeloid and lymphoid lineages, at varied stages of maturity, were assayed with LacCer for the presence of beta 1-3GlcNAcT(i) activity. Our results indicate that myeloid cells contain this initiating beta 1-3GlcNAcT(i) activity, whereas lymphoid cells do not. This is consistent with our thin-layer chromatography immunostain results which show that all myeloid cell lines express neutral neolacto glycosphingolipids and lymphoid cells do not. Our findings suggest that the presence of the initiating activity only in myeloid cells is a regulatory factor in the expression of neutral neolacto glycosphingolipids in human leukocytes. We also tested both myeloid and lymphoid cell lines for the presence of elongating beta 1-3GlcNAcT(i) activity (reaction (ii) above) by using neolactotetraosylceramide as an acceptor. Our results show that an elongating activity is expressed by all myeloid and lymphoid cell lines tested. Initiating (myeloid) and elongating (myeloid and lymphoid) activities were distinguished by several characteristics: metal ion activation, pH optimum, and kinetic constants. In conclusion, our results indicate the presence of two beta 1-3GlcNAcT(i) activities in human leukocytes: one that catalyzes the initial reaction and is found only in the myeloid lineage and one that catalyzes the elongating reaction and is found in both myeloid and lymphoid cells. PMID- 8489256 TI - The effects of castanospermine and swainsonine on the activity and synthesis of intestinal sucrase. AB - Castanospermine is an indolizidine alkaloid that is found in the seeds of the Australian tree Castanospermum australe. These seeds have been reported to be toxic to animals and to cause severe gastrointestinal upset. In order to determine whether castanospermine is responsible for this toxicity, the alkaloid was injected into young mice or rats, and its effects on various intestinal disaccharidases were determined. Another indolizidine alkaloid, the alpha mannosidase inhibitor swainsonine, was also tested to compare its effects to those of castanospermine. Castanospermine strongly and rapidly inhibited the activity of the disaccharidases, sucrase, maltase, and trehalase, with sucrase being the most sensitive to inhibition. The loss of activity of these enzymes, especially sucrase, in injected animals appeared to be due to a direct inhibition of enzyme activity, rather than to a change in the structure of the glycan chains of the enzyme, since only minor alterations in carbohydrates were observed. On the other hand, swainsonine, when injected into animals, also profoundly decreased the activity of the sucrase, but this alkaloid had no direct effect on sucrase activity although it did markedly alter the carbohydrate nature of this glycoprotein. This change in oligosaccharide structure may affect protein conformation, stability, or targeting, any or all of which may in turn affect activity. In in vitro studies with the purified enzyme, castanospermine was found to be a competitive inhibitor of intestinal sucrase, but it was a noncompetitive inhibitor of intestinal maltase. A number of other glucosidase inhibitors that inhibit sucrase activity in vitro are also described. PMID- 8489257 TI - Biosynthesis of vernoleate (cis-12-epoxyoctadeca-cis-9-enoate) in microsomal preparations from developing endosperm of Euphorbia lagascae. AB - Epoxidated fatty acids are the major constituents of the triacylglycerols in a few plant species. We have investigated the biosynthesis of vernolic acid (cis-12 epoxyoctadeca-cis-9-enoic acid) in the seed oil of Euphorbia lagascae. Microsomes were isolated from developing endosperm. The membrane lipids were labeled in situ with [14C]oleate or [14C]linoleate, which mainly were recovered in phosphatidylcholine (PC), and the metabolization of the radioactive fatty acids was followed in incubations with or without NADPH. In the presence of NADPH, [14C]vernoleate was formed. After short incubations, most of the vernolic acid was found in PC, but with increasing incubation times, the free acid dominated. The synthesis of vernoleate was inhibited by carbon monoxide, but not by cyanide. The presence of anticytochrome b5 antibodies inhibited both the desaturation of [14C]oleate to [14C]linoleate and the epoxidation of [14C]linoleate to [14C]vernoleate. Free linoleic acid did not serve as substrate for epoxidation. The results indicate that, in the endosperm of E. lagascae, vernoleate is synthesized on PC from linoleate, and that the epoxidation is catalyzed by a cytochrome P450 and involves cytochrome b5. PMID- 8489258 TI - Induction of Schistosoma mansoni glutathione S-transferase by xenobiotics. AB - The effects of 3-methylcholanthrene, butylated hydroxyanisole, and phenobarbital on the expression of glutathione S-transferase (GST, EC 2.5.1.18) were examined in the human parasite Schistosoma mansoni. GST specific activity toward 1-chloro 2,4-dinitrobenzene increased by 170% in parasites recovered from mice injected with 3-methylcholanthrene and 230% in parasites recovered from mice maintained on a diet containing butylated hydroxyanisole. These increases in specific enzyme activity were paralleled by accumulation of mRNA hybridizing to pGT16.4, a cDNA clone that encodes the most abundant GST subunit, SmGST-3. Northern hybridization analysis showed a 5-fold increase in mRNA hybridizing to pGT16.4 72 h after exposure to 3-methylcholanthrene, a 10-fold increase after 12 days exposure to butylated hydroxyanisole, and a 6-fold increase 16 h after treatment with phenobarbital. In contrast, no accumulation of mRNA hybridizing to either of two other cDNA clones that encode the SmGST-4 and SmGST-6 subunits was detected. Hybrid select translation using pGT16.4 combined with reverse-phase high-pressure liquid chromatographic analysis demonstrated that in addition to SmGST-3 mRNA, the clone also hybridized to mRNA species encoding the SmGST-1 subunit, a member of the same isoenzyme family. High-pressure liquid chromatographic analysis of GST affinity purified from butylated hydroxyanisole-exposed parasites revealed a 2.5-fold increase in the concentration of SmGST-1 and SmGST-3 present compared with an equivalent amount of tissue from control organisms. There was no change, however, in the SmGST-1 to SmGST-3 ratio (1:6), indicating that both subunits were induced to the same extent by this agent. The results of these studies suggest that alterations in GST expression may influence the parasite's survival within the host environment. PMID- 8489259 TI - Inhibition of protein radical reactions of ferrylmyoglobin by the water-soluble analog of vitamin E, Trolox C. AB - The reactivity of Trolox C, a water-soluble analog of vitamin E, toward protein radicals formed during the oxidation of metmyoglobin and the therefrom derived molecular products was examined in terms of the ability of the phenolic antioxidant to prevent specific oxidative reactions involving tyrosyl radicals and to reduce the molecular products to functional hemoproteins. (i) Trolox prevented the oxidative reactions initiated upon oxidation of the hemoprotein by H2O2 and involving tyrosyl radicals: on one hand, it inhibited the covalent binding of protein to the heme group and, on the other hand, it inhibited dimerization of sperm whale myoglobin, the latter process entailing the intermolecular covalent binding of tyrosines. The inhibition of both processes required concentrations of Trolox 20- to 50-fold higher than those needed to reduce the hypervalent heme iron to its ferric form. Likewise, Trolox inhibited dimerization and polymerization of sperm whale myoglobin upon its treatment with chloroiridate, a process associated with formation of tyrosyl radicals and negligible oxidation of the heme iron. However, these results did not provide unambiguous evidence for the reactivity of the phenolic antioxidant toward amino acid radicals in myoglobin, for Trolox displayed a high reactivity toward the oxidant, chloroiridate. (ii) The stable oxidation product originating from sperm whale myoglobin oxidation, i.e., the dimeric hemoprotein, was redox active, inasmuch as it retained its capacity to form an oxy complex upon reduction and an oxoferryl complex upon oxidation by H2O2. The latter complex was reduced by Trolox to a compound which exhibited a 10- to 12-nm blue shift of the 632-nm absorption typical of the native metmyoglobin. Although this absorption shift was likely to express oxidative modifications of the porphyrin ring, the modified hemoprotein retained its capacity to react with peroxides and displayed a peroxidative activity. PMID- 8489260 TI - Interaction between the C-terminal peptides of tubulin and tubulin S detected with the fluorescent probe 4',6-diamidino-2-phenylindole. AB - The digestion of tubulin with subtilisin and the reassociation of the digestion products was followed by means of the fluorescent probe 4',6-diamidino-2 phenylindole (DAPI). The fluorescence spectra of DAPI bound to chicken brain tubulin and to the main products of tubulin digested with subtilisin-agarose (tubulin S and C-terminal peptides) were analyzed. The corrected emission spectrum of DAPI in the presence of tubulin showed an enhancement of fluorescence intensity with a maximum at 452 nm. The digestion reaction was followed by the diminution of the area of DAPI-tubulin emission spectra, which showed biphasic pseudo-first-order kinetics. The values for the rate constants were 1.2 x 10(-2) min-1 and 3.5 x 10(-2) min-1 for the alpha and beta subunits, respectively, and were similar to those determined from the undigested subunits using polyacrylamide gel electrophoresis. Tubulin S and the C-terminal peptides were purified by means of a Bio-Gel P-60 column. The C-terminal peptides obtained from this column were analyzed by urea-sodium dodecyl sulfate polyacrylamide gel electrophoresis, and an apparent molecular weight around 3000 was determined. The corrected emission spectrum of DAPI in the presence of tubulin S showed a maximum shifted to 460 nm and a lower enhancement of fluorescence than the emission spectrum of the DAPI-tubulin complex. Titration of purified tubulin S with the C terminal peptides of tubulin showed, after the addition of DAPI, an increase in the fluorescence intensity at 460 nm with a saturation function dependent on the concentration of peptides added. On the other hand, the emission spectrum of DAPI in the presence of the C-terminal peptides was unchanged from that of free DAPI in the solution. From these results we propose that the DAPI binding site is located on tubulin S and that the C-terminal peptides interact with tubulin S after digestion with subtilisin. PMID- 8489261 TI - The hydroxylation of plant diterpene analogues by the fungus Syncephalastrum racemosum. AB - Triepoxide diterpenes isolated from the perennial herb, Tripterygium wilfordii, have shown promising antileukemic and anti-inflammatory activity in vitro and in vivo. However, the toxicity of these epoxides has limited their clinical usefulness and analogues are sought which possess the pharmacological actions but have a lower toxicity. In this study, we have generated oxidized analogues of these diterpenes from a synthetic lactone precursor (19-hydroxy-18 (4-3) abeo abieta-3,8,11,13-tetraen-18-oic acid lactone) by incubating the lactone with the Zygomycete fungus, Syncephalastrum racemosum. Incubation of lactone with S. racemosum in liquid media yielded four distinct polar metabolites as determined by thin-layer chromatography of ethyl acetate extracts. Column purification followed by structural analysis by 1H NMR and mass spectroscopy revealed these compounds to be 7-beta-hydroxylactone, 7-alpha-hydroxylactone, 15-hydroxylactone, and 7-ketolactone. When lactone was added to 48-h-old cultures, 7-beta hydroxylactone appeared after 30 min whereas there was a 4-h lag period before the 7-alpha-hydroxy and 15-hydroxy metabolites were detected suggesting that enzyme induction was necessary before metabolism occurred. The 7-ketolactone was not detected until 24 h of incubation and this may represent a nonenzymatic oxidation of 7-hydroxylactone. The addition of various cytochrome P450 inhibitors (ketoconazole, miconazole, alpha-naphthoflavone, aminobenzothiazole, and carbon monoxide) to liquid cultures prevented the 15-hydroxylation of lactone. Interestingly, in contrast to the other agents, ketoconazole and miconazole (20 microM) were not able to inhibit 7-hydroxylation even though 15-hydroxylation was inhibited by these agents. With the exception of carbon monoxide, cell growth was unaffected by these agents. These data suggest that the biotransformation of diterpenes by S. racemosum was mediated by an inducible hydroxylase system which is sensitive to cytochrome P450 inhibitors and that more than one hydroxylase enzyme may be responsible for the observed products. PMID- 8489262 TI - Evidence that catalase is a major pathway of ethanol oxidation in vivo: dose response studies in deer mice using methanol as a selective substrate. AB - Recently, it was demonstrated that 4-methylpyrazole was not only an inhibitor of alcohol dehydrogenase but also caused competitive inhibition of fatty acyl-CoA synthetase, the enzyme which activates fatty acids (B. U. Bradford, D. T. Forman, and R. G. Thurman, 1993, Mol. Pharmacol. 43, 115-119). Rates of catalase dependent alcohol metabolism were decreased in alcohol dehydrogenase-negative (ADH-) deer mice because the H2O2 supply for catalase via peroxisomal fatty acid oxidation was inhibited due to substrate limitation. In light of these findings it became necessary to reevaluate the role of catalase and alcohol dehydrogenase in alcohol metabolism. In this study, methanol, a selective substrate for catalase in rodents, was compared with ethanol. Rates of ethanol and methanol metabolism were studied in vivo at blood alcohol levels ranging from 50 to 500 mg/dl. In the ADH- deer mouse, rates of methanol and ethanol metabolism increased when alcohol was elevated from 0 to 100 mg/dl and were maximal at values around 6 8 mmol/kg/h (half-maximal rates were observed at blood alcohol levels around 50 mg/dl). In the ADH+ deer mouse, rates of ethanol metabolism increased to values around 9 mmol/kg/h at 100 mg/dl and remained constant at blood levels up to 500 mg/dl. In contrast, rates of methanol metabolism increased to values of only 5 mmol/kg/h at levels of 100 mg/dl (the half-maximal rate was about 2.5 mmol/kg/h at 50 mg/dl) followed by a steady increase to 9 mmol/kg/h as the blood level was increased from 100 to 500 mg/dl (the half-maximal rate for this second component was around 6 mmol/kg/h at 300 mg/dl). Rates of methanol uptake were 50 +/- 4 nmol/min/mg protein in 10,000g pellets from ADH- deer mouse livers; however, methanol was not metabolized by isolated microsomes. The catalase inhibitor aminotriazole decreased ethanol and methanol metabolism 75% in ADH- deer mice. Further, olive oil, which is rich in oleate, increased methanol metabolism from 7 to 11.5 mmol/kg/h. This stimulation was blocked by fructose, which diminishes ATP and decreases H2O2 supply. In the ADH+ deer mouse, fructose (2 g/kg) stimulated ethanol metabolism as expected; however, inhibition of both ethanol and methanol metabolism was observed with higher doses of fructose (10 g/kg). Taken together, these data support the hypothesis that catalase is the predominant pathway for alcohol metabolism in the ADH- deer mouse. The contribution of catalase was about 50% in the ADH+ mutant at low doses of ethanol and approached 100% as the alcohol concentration was elevated. PMID- 8489263 TI - The amino acid sequence of Pseudomonas putida azurin. AB - The low molecular weight "blue" copper protein, azurin, has been purified from Pseudomonas putida (NCIB 9869) to homogeneity using various chromatographic techniques including reverse-phase HPLC. The amino acid sequence of the N terminus of the reduced and carboxymethylated protein yielded a single sequence corresponding to AECKV. The complete sequence, comprising 128 amino acid residues with a C-terminal sequence corresponding to TVTLK, was determined from the peptides obtained from a Staphylococcus aureus V8 digest of the protein and confirmed using peptides obtained following cyanogen bromide and endoprotease Asp N digests. The amino acid sequence contained three cysteine residues at positions 3, 26, and 112, was devoid of tryptophan, and showed closest similarity (90% identical residues) to the previously determined sequence of azurin isolated from Pseudomonas fluorescens biotype B [Ambler, R.P. (1971) in Developpements Recents Dans L'Etude Chimique De La Structures Des proteins (Preverio, A., Pechere, J. F., and Coletti-Preverio, M.-A., Eds.), pp. 289-305, INSERM, Paris]. Examination of the complete sequence indicated P. putida azurin contained unique Asp and Ala residues at positions 19 and 21, respectively, that have not been found in any other azurin sequence. PMID- 8489264 TI - The skeletal muscle transverse tubular Mg-ATPase: identity with Mg-ATPases of smooth muscle and brain. AB - Purified chicken skeletal muscle transverse tubule (T-tubule, TT) membrane preparations contain a very active Ca- or Mg-ATPase (EC 3.6.1.3) previously thought to be a T-system-specific marker enzyme. The function of the Mg-ATPase has not yet been determined although its prominent activity and concentration in junctional complexes supports a possible role in the excitation-contraction cycle. An essential component of the Mg-ATPase has been identified as a M(r) 85,000 glycoprotein (85k-GP). Polyclonal antibodies raised against the TT 85k-GP were specific and exhibited no cross-reactivity with other skeletal muscle proteins on immunoblots. Using this anti-85k-glycoprotein IgG, we have explored other chicken tissues to determine the tissue distribution of the 85k-GP. Antibody reactive polypeptides of M(r) 85,000 were found in gizzard smooth muscle, brain, heart, spleen, and lung tissue. The brain and smooth muscle membrane proteins were further purified and characterized for 85k-GP-associated Mg-ATPase activity. The brain and smooth muscle enzymes exhibited properties indistinguishable from the skeletal muscle TT-specific Mg-ATPase with regard to a series of activators and inhibitors, amino terminal amino acid sequences, and the effects of deglycosylation. The enzyme in all three tissues was inhibited by the diacylglycerol kinase inhibitor R 59022. Identification of the TT Mg-ATPase in gizzard smooth muscle has allowed the investigation of the Mg-ATPase membrane topology using isolated whole smooth muscle cells. The data support an ecto orientation for the smooth muscle cell enzyme. Although the orientations of the brain and skeletal muscle enzymes have not been conclusively determined, the nearly identical properties of all three enzymes argues for an ecto-orientation of the active sites of these enzymes as well. The responsiveness of the three enzymes to regulatory lipids suggests that the ecto-Mg-ATPase may serve as a master switch controlling extracellular ATP concentrations and ligand accessibility to P1- and P2-purinoceptors. It is also proposed that the ecto MgATPase may regulate ATP accessibility to ectoprotein kinases in a variety of tissues, and, in brain, the ecto-MgATPase may modulate the neurotransmitter role of ATP. PMID- 8489265 TI - Deoxyribonuclease of Syncephalastrum racemosum--enzymatic properties and molecular structure. AB - Among the isolated fungal species of soil, one filamentous fungus, Syncephalastrum racemosum, produces a relatively large amount of DNase. This enzyme has been purified to apparent homogeneity by column chromatography on DEAE cellulose, hydroxylapatite, phenyl-Sepharose CL-4B, and Sephadex G-100. The active enzyme requires divalent metal ions and has an optimum pH of 7.0 with Mg2+ and 7.2 with Mn2+. This enzyme is an acidic glycoprotein with a pI 5.0 and is relatively unstable at low concentrations. The M(r) of the enzyme is 56,000 during gel filtration under nondenaturing conditions but is 28,000 during polyacrylamide gel electrophoresis in sodium dodecyl sulfate. These results suggest a structure consisting of two subunits. The subunits of the holoenzyme can be cross-linked with glutaraldehyde. The yield of N-terminal phenylthiohydantoin-alanine from the holoenzyme is 140% and that of one peptide (D-Y-V-S-S-G-Y-D-R), obtained from the tryptic digest is 160%, indicating that the native enzyme is composed of two identical subunits and probably has two active domains. Fungal DNase can be inactivated by Cu(2+)-iodoacetate under conditions that inactivate bovine pancreatic DNase. The specific activity (units/mg of protein) of fungal DNase is 6.5 times that of bovine DNase. The amino acid content of fungal DNase, relative to bovine DNase, is higher in Gly and lower in Ser and Val. The fungal N-terminal 40-residue sequence shows a high degree of homology with a consensus sequence derived from DNase of three mammalian species. PMID- 8489266 TI - Participation of P450 3A enzymes in rat hepatic microsomal retinoic acid 4 hydroxylation. AB - Cytochrome P450-mediated 4-hydroxylation is an important pathway in the termination of the biological action of retinoids. Several purified mammalian hepatic P450s have been shown to catalyze the 4-hydroxylation of all-trans retinoic acid (retinoic acid) in reconstituted enzyme systems, but the nature of the activity in untreated rat liver microsomes has not been defined. In the present study, microsomal retinoic acid 4-hydroxylation was characterized in untreated liver from rats of both sexes and after a series of induction treatments. Thus, dexamethasone and phenobarbital, but not beta-naphthoflavone or dimethyl sulfoxide, increased the activity in male and female rats. An immunoglobulin G (IgG) fraction raised against P450 3A1 decreased the rate of retinoic acid 4-hydroxylation in untreated rat hepatic microsomes, but IgG directed against the P450s 2C11, 2B1, and 2C6 were noninhibitory. In vivo administration of triacetyloleandomycin, which has been shown to form a metabolite intermediate complex with P450 3A, followed by potassium ferricyanide oxidation in vitro, reactivated retinoic acid 4-hydroxylation and androst-4-ene 3,17-dione 6 beta-hydroxylation similarly (to 154 and 152% of the respective activities in the absence of potassium ferricyanide). Finally, exogenous retinoic acid (60 mg/kg ip for three days) markedly increased the rate of retinoic acid 4 hydroxylation in hepatic microsomes from male and female rats (3.8- and 3.7-fold, respectively). This occurred without comparable increases in other P450 activities. Despite these findings, the age- and sex-related profiles of microsomal retinoic acid 4-hydroxylation were clearly different from those measured for other P450 activities. Thus, on the basis of xenobiotic pretreatment, developmental, and immunochemical studies, the enzyme(s) involved in constitutive retinoic acid 4-hydroxylation appears distinct from a number of well-described P450s in untreated and induced rat liver. The data are consistent with the partial involvement of P450(s) from the 3A subfamily in retinoic acid 4 hydroxylation, but it seems clear that P450s 3A1 and 3A2 do not participate in this activity. PMID- 8489267 TI - Localization of free and bound biotin in cells from green pea leaves. AB - Cytosol and vacuoles from protoplasts, chloroplasts, and mitochondria from green pea (Pisum sativum) leaves were purified and examined for their biotin content. The bulk of free biotin was shown to be exclusively associated with the cytosolic fraction at a concentration of about 4 pmol/mg protein and no bound biotin was detected. The bulk of bound biotin (biotin-containing carboxylases) was associated with the soluble fraction of chloroplasts and mitochondria at a concentration of about 1.2 and 13 microM, respectively. No free biotin was detected in these organelles. Western blot analysis of total, chloroplastic, and mitochondrial polypeptides, using horseradish peroxidase-labeled streptavidin, revealed three biotin-containing polypeptides with molecular mass of 220,000, 76,000 and 34,000. All were detected in the total pea leaf extract, but the M(r) 76,000 and the M(r) 34,000 biotinylated polypeptides were only detected in mitochondria and chloroplasts, respectively. 3-Methylcrotonyl-coenzyme A carboxylase and acetyl-coenzyme A carboxylase activities were measured in these two compartments, respectively. Previously, it has been shown that the M(r) 76,000 polypeptide was the biotinylated subunit of the mitochondrial 3 methylcrotonyl-coenzyme A carboxylase. In this paper, the origin and putative function of free biotin located in cytosol are discussed. PMID- 8489268 TI - Hormonal regulation of rat uterine collagenase. AB - Two different methods of study have been employed in the analysis of the hormonal regulation of rat uterine collagenases. The first is concerned with the enzyme activity and the second, its synthesis. The data presented in this report reveal that the rat uterine collagenase is under the regulatory influence of both estradiol and progesterone. This fact is first exemplified by the observation that on Day 2 post-ovriectomy, a wave of collagenase synthesis takes place which influences the enzyme activity in the uterus during the next 3-4 days. This peak in collagenase synthesis disappeared in the uteri of rats subjected to ovariectomy and adrenalectomy simultaneously. It indicated that a hormone of adrenal origin was responsible for the enhanced synthesis and activity of collagenase in the uteri of ovariectomized rats. That the hormone involved was progesterone was shown by the subsequent experimental data. The estradiol mediated enhancement in rat uterine collagenase activity has been shown to be inhibited by intraluminal exposure of the uteri to actinomycin D/cyclohexinmide, indicating the apparent influence of the hormone at the level of the collagenase gene. PMID- 8489269 TI - Vitamin D deficiency suppresses cell-mediated immunity in vivo. AB - Severe vitamin D deficiency has been produced in mice as evidenced by severe hypocalcemia and an absence of 25-hydroxyvitamin D in blood. Vitamin D deficiency was accompanied by a slight decrease in body weight and food consumption. Vitamin D-deficient and vitamin D-sufficient mice were sensitized with dinitrofluorobenzene (DNFB). Sensitivity to DNFB was determined by treatment of one ear with DNFB. The ratio of thickness of the treated ear to that of nontreated ear was used as an index of cell-mediated immune reaction. The incorporation of [3H]thymidine into the DNA of the ear was also used as an index of cell-mediated immunity as was the response of thymus lymphocytes to concanavalin A. Vitamin D deficiency markedly decreased the ear thickness ratio and the [3H]thymidine incorporation ratio in DNFB-sensitized mice. Similarly, the incorporation of [3H]thymidine into the DNA of concanavalin A-treated thymus lymphocytes from DNFB-sensitive mice was significantly reduced in vitamin D deficiency. These results show that in vivo vitamin D deficiency impairs cell mediated immunity. The provision of a vitamin D-sufficient diet for 8 weeks corrected the impaired response of the immune system, while vitamin D administration for 3 weeks did not. PMID- 8489270 TI - [Pathology of gastric precancerous lesions: with special reference to present study for genetic abnormality]. PMID- 8489271 TI - [Fluorocytometric DNA analysis of intestinal metaplasia associated with gastric carcinoma]. AB - Histopathologic studies and fluorocytometric DNA analysis were carried out in 39 patients with intestinal metaplasia (IM) of the mucosa associated with gastric carcinoma, in order to determine possible relationships. According to the histological degree of IM, 39 cases were divided into 16 (41%) with slight-to moderate, and 23 (59%) with severe IM. The 39 tumors were histologically divided into 20 (51%) differentiated tumors and 19 (49%) undifferentiated tumors. The DNA patterns of tumors revealed 17 (43%) to be euploidy and 22 (57%) to be aneuploidy. The DNA content of the metaplastic epithelial cells was measured, and the percentage of the cells in S and G2 + M phases of the cell cycle was taken as the index of proliferative activity. DNA analysis of the non-metaplastic epithelium was performed in 10 as a control group. While the histological differentiation of the tumors and the degree of IM were not related to the proliferative activity of IM, the IM around the aneuploid tumors did have higher proliferative activity (14.01 +/- 6.16%) than that around euploid tumors (11.08 +/- 7.13%) or of normal mucosa (9.95 +/- 9.92%). This approach will help to determine cell kinetics of IM around the gastric tumor. Our study indicated a relationship between DNA ploidy and the proliferative activity of IM around gastric cancer. PMID- 8489272 TI - [DNA flow cytometry in smooth muscle tumors of the gastrointestinal tract]. AB - DNA ploidy of 45 smooth muscle tumors of the G.I. tract was determined by flow cytometry and correlated with clinical features and prognosis. The sites of the tumors were: esophagus (1), stomach (24), small intestine (12), large intestine (6), liver (1) and pancreas (1). The histologic type was leiomyoma in 14, leiomyosarcoma in 29, and leiomyoblastoma in 2. DNA aneuploidy was more frequent in leiomyosarcoma (17/29) than leiomyoma (5/14), but the difference was not statistically significant. One leiomyoblastoma was diploid and the other was aneuploid. No patients with leiomyoma died. In patients with leiomyosarcomas, 5 year survival was significantly poorer in those with aneuploid tumors (38%) than in those with diploid tumors (83%). There was no correlation between DNA ploidy and clinico-pathological features of tumors. The present study disclosed that DNA ploidy is a prognostic variable, independent of other variables. PMID- 8489273 TI - [Fluorocytometric DNA analysis of borderline lesions in the large intestine]. AB - A total of 9 surgically resected non-cancerous benign lesions (5 regenerative epithelium, 4 hyperplastic or metaplastic epithelium), 4 normal epithelium, 30 carcinomas and 12 adenomas containing 7 moderate dysplastic epithelium and 5 severe dysplastic epithelium in the large intestine, were used. Then 40 microns thick paraffin sections were made from each specimen, dewaxed, and the target portion was excised under microscopic visualization. Free cells isolated by 0.5% pepsin solution were smeared and followed by DNA staining by DAPI, and fluorocytometric DNA measurement was performed using a fluorocytometer (BH 2.QRFL, Olympus). All specimens of non-cancerous benign epithelium and normal epithelium showed diploidy. The average mean DNA value was 2.03 +/- 0.04 c (1.95 2.10), the percentage of cells above 4.1 c (4.1 c > or = %) averaged 0.26 +/- 0.42% (0-1.25) and the coefficient of variation (CV) averaged 14.30 +/- 3.18% (10.19-19.58). Seven of 30 carcinomas showed diploidy. Among these diploid carcinomas, the mean DNA value averaged 2.30 +/- 1.98 c (2.01-2.71) (p < 0.05), 4.1 c > or = % averaged 4.17 +/- 2.91% (2.0-10.5) (p < 0.05) and CV averaged 32.2 +/- 5.8% (24.43-38.90) (p < 0.01). Based on these results, aneuploid cases were judged to be malignant. In the case of diploidy, if the percentage of cells above 4.1 c was more than 2.0% and CV was more than 24.43%; when the former was less than 1.25% and the latter was less than 19.58%; and when one or both of the two was out of the range described in the above two categories, they were judged to be malignant, benign or borderline, respectively. From these criteria, 7 adenomas showing moderate dysplasia were analyzed as benign in 2, borderline in 4 and malignant in 1, while 5 adenomas evidencing severe dysplasia were analyzed as malignant in 4 and borderline in 1. In conclusion, fluorocytometric evaluation of the malignant or benign tumor of borderline lesions in the large intestine was found to be possible. PMID- 8489274 TI - [Immunohistochemical study of p53 in colorectal polyps]. PMID- 8489275 TI - [Problems in DNA ploidy analysis using flow cytometry--influences from contaminant mononuclear cells]. AB - The present study was undertaken to examine the influences of excessive contamination by lymphocytes on the flow cytometric analysis of DNA ploidy of head and neck cancers. Although lymphocytes which contaminate test cells can serve as an internal control (2C), an excess of these lymphocytes can mask the aneuploid peak of cancers. This tendency was particularly prevalent in well differentiated squamous cell carcinoma. In some cases, most of the cells isolated from tumor-positive HE-stained tissue samples were lymphocytes. This is probably because lymphocytes are likely to survive the cell-isolating procedure, whereas keratocytes are likely to be destroyed during it. If samples excessively contaminated by lymphocytes are subjected to flow cytometry, the aneuploid peak of cancer cells is low relative to the 2C peak, possibly causing an erroneous judgment of diploid. Cytofluorometry, in which a smear of test cells is observed directly to quantify the DNA of cancer cells alone, was useful in detecting lymphocyte-masked aneuploid cells. PMID- 8489276 TI - [Preoperative evaluation of malignant potential in esophageal carcinoma by nuclear DNA contents]. AB - Employing surgically resected specimens from patients without preoperative radiation therapy, we measured the nuclear DNA contents in order to evaluate the malignant potential of esophageal carcinoma. The association of the DNA index (DI) > or = 1.7 and the intratumoral DNA heterogeneity of biopsy specimens from patients with or without preoperative radiotherapy was also analyzed in relation to problems related to preoperative evaluation of nuclear DNA contents using biopsy specimens and the influence of irradiation on nuclear DNA contents. Esophageal carcinomas in 128 cases were studied. Nuclear DNA content was measured for biopsy specimens as well as surgically resected tumors by flow cytometry according to the method of Hedley and colleagues. HET was found in 42% of surgically resected specimens, but in only 18% of biopsy specimens. In 90% of cases, dominant DI of the resected tumor was also found in the biopsy specimens. Cases of DI > or = 1.7 showed a poorer prognosis than those with DI < 1.7 in cases with preoperative radiotherapy (p < 0.05) as well as in those without it. These results indicated that DI can be an indicator for highly malignant potential of esophageal carcinoma when measuring nuclear DNA contents using not only biopsy specimens but also specimens from irradiated cases. PMID- 8489277 TI - [Adverse effect of prolonged formalin fixation on DNA ploidy in paraffin-embedded tissue]. AB - From retrospective analysis of 174 formalin fixed, paraffin-embedded, HCC tissue samples, the possible correlation was investigated between the CV determined by FCM and the duration of formalin fixation. An adverse effect of prolonged formalin fixation on CV and fluorescence intensity in liver tissue was investigated prospectively in samples from 4 patients. PMID- 8489278 TI - [Image analysis on isolated colorectal tumor cells]. AB - Image analysis of the nuclear morphology was performed on propidium iodide stained isolated cells from 9 adenomas and 9 cancers of the colorectum. We analyzed DNA content, seven nuclear geometric features and four shape factors of tumor cells using an image cytometry system that has been developed in our laboratory. Nuclear breadth and the degree of contour irregularity of cancer cells were found to be significantly different from those of adenoma cells. The coefficients of variation (CV) of some nuclear features and the degree of contour irregularity were increased in cancer cells, while CV of the degree of circularity was increased in adenoma cells. Moreover, nuclear in G2 phase were found to be larger and more round than those in G1 phase. These results suggest that cell-cycle-related analysis of nuclear features would be a valid means to assess the nuclear morphology of colorectal tumors. PMID- 8489279 TI - [Analysis of cell proliferation in endoscopically biopsied specimen of the stomal mucosa of the remnant stomach--with special reference to cell cycle and ODC activity]. AB - An attempt was made to investigate the status of cell proliferation in the remnant stomach, using endoscopically biopsied specimens, with cell cycle analysis by flow cytometry (FCM) and ornithine decarboxylase (ODC) activity determination. Fifty-three partially gastrectomized patients (male 33, female 20) were examined. Their mean age was 60.5, and 22 underwent Billroth I (BI), and 30 Billroth II (B II) operation. The mean time elapsing from the initial operation was 4.0 years. Almost all specimens showed DNA diploidy by FCM. The S phase cell percentage was higher in the stomal area, especially in the B II group. Significantly higher ODC activity was recognized in the stomal mucosa especially in the B II group. A significant positive relationship was noted between postoperative duration and ODC activity in the B II group. These results suggest activated cell proliferation in the stomal area of the remnant stomach. Especially in the B II group, cell proliferation increased with time after initial operation. This activated cell proliferation may play some role in the carcinogenesis of the remnant stomach. PMID- 8489280 TI - [Simultaneous measurement of kinetochore protein and DNA by flow cytometry]. AB - We were successful in obtaining simultaneous measurements of kinetochore protein and DNA with flow cytometry using HeLa cells and KM cells; the latter originated with a squamous cell carcinoma of the oral cavity. Kinetochore protein was stained with the serum obtained from a patient with CREST syndrome and FITC conjugated goat antihuman IgG antibody; the DNA was stained with propidium iodide. The FITC fluorescence of cells with a large DNA index was stronger than in cells with a small DNA index. The FITC intensity increased from G1 phase to G2/M phase. The rate of FITC intensity increase representing the kinetochore protein amount was greater in the early and late S phases than in the other phases. The results suggest that kinetochore protein increases in the interphase as the cell cycle unfolds. PMID- 8489281 TI - [Detection of chromosomal aberration using fluorescence in situ hybridization in DNA diploid colorectal carcinomas]. AB - Numerical aberrations of chromosomes can be detected by fluorescence in situ hybridization (FISH), using chromosome-specific probes. It is possible to observe this in solid tumors from which it is very difficult to obtain metaphase nuclei. The present study employed surgical specimens from 15 cases of colorectal carcinoma, all of which showed DNA diploidy. In the same samples, we analyzed chromosomal numerical aberration by FISH according to the method of Pinkel et al. Biotinylated DNA probes specific to chromosome #7, #11 and #17, were used. The hybridization spots were observed by fluorescent microscopy. As a result, the numerical aberrations of chromosomes detected by FISH were found in DNA diploid cases by FCM. They were trisomy and monosomy. These results indicate that FISH is useful to detect the chromosomal aberrations of DNA diploid cases. PMID- 8489282 TI - [The intensity of hst-1 gene amplification and malignant potential of esophageal carcinoma in relation to intratumoral heterogeneity]. AB - Amplification of hst-1 gene is associated with poor prognosis in patients with esophageal carcinoma. Since there is a high frequency of DNA stem-line heterogeneity, we studied intratumoral heterogeneity of hst-1 amplification, and evaluated whether or not the intensity of hst-1 amplification is associated with the malignant potential of esophageal carcinoma. A total of 73 patients with esophageal carcinoma who had undergone esophagectomy were studied. Intratumoral heterogeneity of hst-1 amplification was examined in two to four sections of tumour specimens which showed mainly DNA heterogeneity in 27 of these patients. The judgement of hst-1 amplification in the same tumor was identical in all of the 27 patients, although its intensity was not identical in some cases. And in 73 patients, postoperative recurrence in organs showed a high incidence (78%) in the hst-1 amplification group with a high intensity (over 7-fold). Therefore, hst 1 amplification exceeding 7-fold can serve as an indicator to predict the high grade of malignant potential of esophageal carcinoma. PMID- 8489283 TI - [Flow cytometric analysis of DNA ploidy in colorectal adenoma]. AB - Flow cytometric measurement of nuclear DNA content in 159 colorectal adenomas was carried out to investigate the relationship between DNA ploidy and the histological findings. DNA aneuploidy was detected in 18 lesions (12.8%). The incidence of DNA aneuploidy was significantly higher in tubulovillous adenomas than in tubular adenomas (30.4% vs. 8.1%; p < 0.01). DNA aneuploidy was not found in any adenoma with mild dysplasia, but was noted in 19.1% of those with moderate dysplasia and in 33.3% of those with severe dysplasia. The mean size of the lesions was significantly larger in adenomas with aneuploidy than in those without aneuploidy (14.0 mm vs. 7.7 mm; p < 0.01). The DNA index values of 18 adenomas with aneuploidy were divided into two groups: one ranged from 1.07 to 1.23 and the other from 1.66 to 1.85. DNA index values correlated with the size of the lesions (p < 0.05), but not with the histologic type and degree of dysplasia. PMID- 8489284 TI - [S-phase fraction and malignant potential in DNA diploid colorectal cancer]. AB - Patients with DNA diploid tumor have a significantly longer survival than those with DNA aneuploid in colorectal cancer, but some patients with diploid tumor show poor survival. For assessing malignant potential in diploid colorectal cancer, flow cytometric analysis of S-phase fraction (SPF) was investigated using paraffin-embedded materials from 79 carcinoma patients who had been treated from 1971 to 1989. There was no significant correlation between SPF and clinicopathological factors (such as sex, tumor size, tumor location, macroscopical type, depth of invasion, node metastasis, peritoneal dissemination, liver metastasis and clinical stage). Mean SPF was significantly higher in poorly differentiated type carcinomas than in well differentiated type carcinomas. Patients with higher SPF had a tendency to poorer survival than those with lower SPF. From these results, it was concluded that SPF represents histological differentiation and that SPF may be a prognostic indicator, in diploid colorectal cancer. PMID- 8489285 TI - [Clinical significance of flow cytometric DNA analysis in patients with rectal cancer]. AB - DNA content was measured by flow cytometry using paraffin-embedded material from 148 primary rectal cancers and 10 distant metastatic lesions. DNA ploidy pattern was classified into the following three groups in terms of the DNA index: 1.00 was defined as the diploid group (DP), 1.00 < DNA index < 1.60 as the low aneuploid group (LAP) and > or = 1.60 as the high-aneuploid group (HAP). Primary carcinomas were DP in 26.4%, LAP in 36.5% and HAP in 37.1%. The DNA ploidy pattern of the primary tumor correlated well with clinicopathological findings such as depth of invasion, lymphatic invasion, pathological stage, metastasis to distant organs and curability of the tumor. In patients with HAP tumor after curative operation, the recurrence rate (21.6%) in distant organs was significantly higher than those with DP tumor (2.8%) and LAP tumor (6.4%) [p < 0.05]. Two LAP patients and 8 HAP patients with distant metastatic disease had the same DNA ploidy pattern HAP in the metastatic lesions. These data indicate that tumor DNA ploidy patterns classified into three groups in rectal cancer may play an important role in predicting prognosis, including distant metastasis. PMID- 8489286 TI - [Analysis of p53 expression and DNA ploidy pattern in colorectal cancer]. AB - An immunohistological staining for p53 conducted in 114 cases of colorectal cancer. The background risk factors such as pathological and DNA ploidy patterns were analized in all cases. p53 was found in 50.0% (57/114). There was a slight increase in p53 positive cases in the advanced cancers, but it was not statistically significant. Five-year survival rates of Dukes B and C were 42.2% for p53-positive cases and 67.2% for p53-negative cases. There was a statistical difference (p < 0.05), but none in the Dukes A group. Study of p53 in combination with DNA ploidy patterns revealed an even greater disparity in survival rates (p < 0.01) between p53-positive aneuploid cases and p53-negative diploid cases. These results indicate that the staining of p53 in conjunction DNA ploidy patterns may be a useful indicator of prognosis in the cases of colorectal cancer. PMID- 8489287 TI - [Preoperative prediction of gastric cancer development by in vitro labelling index of bromodeoxyuridine]. AB - In vitro labelling index (L.I.) of bromodeoxyuridine (BrdU) was evaluated as a preoperative predictor of gastric cancer development. Biopsy specimens were obtained endoscopically from 187 gastric cancer patients preoperatively. Specimens were incubated in RPMI containing BrdU under carbogen gas at 3 times atmospheric pressure. They were fixed and embedded in paraffin. After slicing and dewaxing, they were denatured in 2N HCl. Then BrdU were stained by ABC method and labelling index was calculated. Patients with L.I. more than 10% had a significantly higher risk of lymph node involvement (p < 0.001) and venous invasion (p < 0.05). Those with L.I. more than 20% had a significantly higher risk of liver metastasis (p < 0.01), while patients with L.I. more than 25% had a significantly higher risk of submucosal invasion (p < 0.01). In conclusion in vitro BrdU labelling is a technique available as a preoperative predictor of node involvement, venous invasion, submucosal invasion and prognosis in gastric cancer. PMID- 8489288 TI - [Effect of neoadjuvant chemotherapy (CDDP.UFT therapy) upon cell DNA analysis by flow cytometry in gastric carcinoma]. AB - Neoadjuvant chemotherapy with CDDP and UFT was performed on far advanced gastric carcinoma cases whose curative resection was impossible. These trials were carried out on 10 patients who had Borrmann 4 type carcinoma. PR was found in 6 cases, for an efficacy rate of 60% (6/10). The DNA content in gastric carcinoma was determined before and after treatment by flow cytometry. The relationship between the change of DNA ploidy pattern and effects of chemotherapy was investigated. Aneuploidy was found in 6 of 10 patients (60.0%). DNA ploidy patterns showed no correlation with effectiveness. In aneuploid cases, the group of responders showed seemingly the change of ploidy pattern, from aneuploid to diploid. In non-responders the percentage of aneuploid cells increased. In diploid cases, an accumulation of S-phase fraction was observed in the group of responders. These results suggested that DNA ploidy analysis may provide additional diagnostic criteria for better assessment of chemotherapeutic effects. PMID- 8489289 TI - [Diagnostic value of DNA ploidy in epithelial elevated lesions of the stomach]. AB - Using flow cytometry, we evaluated the diagnostic usefulness of DNA aneuploidy in epithelial elevated lesions of the stomach. Four biopsy specimens were obtained from each lesion in 14 elevated early cancers, 21 adenomas, 37 hyperplastic polyps and 11 cases of chronic gastritis with intestinal metaplasia. All samples obtained from benign lesions indicated diploidy. DNA aneuploidy was detected in 12 lesions (85.7%) of early cancers. DNA indices ranged from 1.10 to 1.19 in six of 10 intramucosal cancers with DNA aneuploidy. Meanwhile, a total of two submucosally invasive cancers had stemlines with a DNA index of more than 2.00. Four early cancers, including two submucosally invasive ones, had multiple aneuploid stemlines. DNA aneuploidy is a useful marker of malignancy in epithelial elevated lesions of the stomach. A higher DNA index and multiple aneuploid stemlines may be possible markers of submucosal invasion in early cancer. PMID- 8489290 TI - [DNA-cytofluorometric, histopathological and immunohistochemical analyses of pancreatoduodenal cancers]. AB - To study the cell characteristics of relatively small pancreatoduodenal cancers (less than 4 cm in the greatest dimension in histopathological examination), we analyzed the relation between the cell kinetics, and histopathological and immunohistochemical findings. Tumors were classified into t1 (0-2 cm in its greatest dimension) and t2 (2-4 cm). We analyzed DNA contents of five tumors of t1 and twelve of t2 by cytofluorometry. Histopathological and immunohistochemical (CA19-9 and CEA) examinations were also carried out. Nuclear DNA content histograms of the tumors in the t1 group showed all diploid pattern, while those in the t2 group exhibited 4 diploid, 7 euploid polyploid and 1 aneuploid patterns. Invasions to the lymphatic (ly), vein (v) and nerve (pn) were found in five cases of diploid tumors (3 of t1 and 2 of t2) and all (8 in t2) of non diploid tumors. A medullary pattern of tumor growth was only noted in three tumors of t1. This pattern was not found in t2 (4 diploid, 8 non-diploid). These results suggest that the cellular DNA content increased in association with the tumor growth in size. In the histopathological findings, both the invasions (ly, v, pn) and fibrosis of the stroma more often appeared as the tumor size and polyploid and aneuploid cells increased. However, other histopathological findings and the immunohistochemical examination for CA19-9 and CEA had no relation to the tumor growth and the DNA ploidy pattern. PMID- 8489291 TI - [Nuclear DNA ploidy pattern and cytological atypia in aspiration cytology of breast cancer]. AB - The relationship between nuclear DNA ploidy pattern and cytological atypia in aspiration cytology of breast cancer was studied in 40 cases of primary breast cancers (T1: 14 cases; T2: 26 cases). They were divided into two groups, according to cytological specimens, high degree (H group) and low degree (L group). Twelve of 40 cases were classified into H group and 28 cases into L group. Fresh frozen materials were obtained from mastectomy specimens and nuclear DNA analysis was carried out by flow cytometry (FCM). Estrogen receptor (ER) and progesterone receptor were measured with the DCC method. Lymph node metastases were histologically seen in 17 cases; the ER positive rate was 55.0%, and the PgR positive rate was 42.5%. FCM revealed 21 cases (52.5%) with diploidy pattern and 19 cases (47.5%) with aneuploidy pattern. S-phase fraction in 17 cases (48.6%) exceeded 20%. L group had more diploid cases and ER positive cases than H group (p < 0.05, p < 0.01). No differences in other factors were seen between the two groups. In diploid cases, L group had more ER positive cases than H group (p < 0.02). PMID- 8489292 TI - [Influences of 5'-deoxy-5-fluorouridine (5'-DFUR) on cell cycle in patients with breast cancer]. AB - Recently, the effectiveness of preoperative chemotherapy for cancer treatment has attracted much attention. The authors conducted a study to investigate the influence of 5'-DFUR administration on the cell cycle, based on DNA analysis using FCM in patients with breast cancer. A total of 53 patients with breast cancer (Stages I, II and III) were investigated concerning tumor PyNPase activity and cell cycle phase. Subjects were stratified according to tumor diameter, histologic type and ER in the group receiving preoperative 5'-DFUR administration (25 patients) and the group not receiving 5'-DFUR (28 patients). The subjects in the group on 5'-DFUR preoperative administration were classified into three sub groups according to total dosages of 400 mg (8 patients), under 4,800 mg (8 patients) and 4,800 mg or over (9 patients). In terms of tumor diameter, significant increases (p = 0.027) of S-phase were observed in patients with the diameters of 5 cm or more in the sub-group of under 4,800 mg dosage. Similar tendencies were seen in all drug administration groups (p = 0.05). However, no influence was observed on S-phase in the group without 5'-DFUR administration. In terms of ER stratification, ER(-) patients in the dosing groups showed increasing tendencies in S-phase and significant differences of G1- as well as G2+M phases. No differences in PyNPase activity were noted in each stratified group. Preoperative administration of 5'-DFUR resulted in alterations of cell cycle in breast cancers. In patients with a total drug dosage of under 4,800 mg and with tumor diameters of 5 cm or more, increases of S-phase and decreases of G1-phase were observed. It was suggested that 5'-DFUR acted in DNA synthesizing stage to accumulate S-phase inhibiting cell cycles. Consequently, this drug is considered useful for neoadjuvant chemotherapy. PMID- 8489293 TI - [Evaluation of chemosensitivity test for cancer using the collagen gel embedded culture system--DNA ploidy pattern and chemosensitivity]. AB - The authors previously reported the advantages of a collagen gel embedded culture system for chemosensitivity tests for cancer. In this report, the chemosensitivities of surgically resected specimens were evaluated by the collagen gel embedded culture system and compared with the DNA ploidy pattern, measured by flow cytometry. The chemosensitivity and DNA ploidy pattern were determined in 11 patients with lung cancer, 8 with gastric cancer and 46 with colorectal cancer. Anticancer agents were MMC and CDDP at Cmax for one hour of exposure, and 5-FU, VDS, VP-16 and ADM at one tenth the Cmax for 24 hours of exposure. Results were compared with those of DNA histogram. In eight lung cancers which were demonstrated to be sensitive by the collagen gel system, 5 showed DNA aneuploidy (DA) and 3 DNA diploidy (DD). Seven cases (87.5%) of gastric cancer were demonstrated to be sensitive with the collagen gel system. Two of them showed DA and five DD. On the other hand, 19 cases (41.3%) of colorectal cancer were found to be sensitive, and 7 of them showed DA and twelve DD. Lung cancer and gastric cancer exhibiting aneuploidy demonstrated sensitivity with the collagen gel system, but the rate of sensitivity was only 28% in colorectal cancer, and even aneuploidy cases showed a low sensitivity. PMID- 8489294 TI - [Protooncogene c-myc amplification and cell cycle analysis in human malignant tumors]. AB - As predictors of tumor response by radiotherapy, tumor with or without c-myc amplification and DNA histogram pattern were analyzed and evaluated for patients' prognosis. There was no relation between c-myc amplification and DNA ploidy pattern in this study. These factors also showed no relation to response rate and survival. But all of the tumors with c-myc amplification and aneuploid pattern exhibited a complete response by radiotherapy. The tumors with c-myc amplification and aneuploid pattern may be more radiosensitive than without amplification and diploid. These data suggested that c-myc amplification and ploidy pattern might be a predictive parameter before radiotherapy. PMID- 8489295 TI - [Estimation of proliferative activity of experimental tongue papillomas and carcinomas in rats--comparison with DNA cytofluorometric analysis and silver stained nucleolar organizer regions]. AB - Eleven tongue papillomas and 25 tongue carcinomas were produced in rats by the oral administration of 0.001% 4-nitroquinoline 1-oxide (4 NQO) in drinking water, and tumor kinetics were investigated by both DNA cytofluorometry and Ag-nucleolar organizer regions (Ag-NORs) staining. The histopathologic characteristics, the mean Ag-NOR number per cell and DNA ploidy patterns were compared. The mean Ag NOR number was least in normal epithelium, more numerous in papillomas and highest in squamous cell carcinomas. The differences were statistically significant. All cases of normal epithelium and papilloma showed a diploid pattern. Eighteen cases of the squamous cell carcinomas (72%) showed a diploid pattern, and 7 cases (28%) exhibited a diploid plus tetraploid pattern. There was a significant difference in the mean Ag-NOR number between the two groups of squamous cell carcinomas. These results suggest that the mean Ag-NOR number may reflect the cell kinetics in the process of carcinogenesis and polyploidization of carcinomas. PMID- 8489296 TI - [Early phase II study of Idarubicin, a new anthracycline anticancer drug, in acute leukemia. Idarubicin Study Group]. AB - An early phase II study of Idarubicin was performed in patients with acute leukemia. The dosages administered were 10 mg/m2, 12 mg/m2, or 15 mg/m2 by iv bolus, once daily for 3 consecutive days. The treatment was given to 47 patients who were in relapse or whose diseases had been refractory to remission induction therapy. Of the 47 patients, 35 were evaluable for response. The patients who showed a response (complete or partial remission) were 9 of 14 patients (64.3%) in the 10 mg/m2 group, 1 of 12 patients (8.3%) in the 12 mg/m2 group, and 3 of 9 patients (33.3%) in the 15 mg/m2 group, respectively. Remissions were achieved in 10 of 23 (43.5%) patients with acute myelogenous leukemia, and in 3 of 6 (50.0%) of those with chronic myelogenous leukemia in blast crisis. However, no remission was achieved in 6 patients with acute lymphocytic leukemia. As for patients who had received prior anthracycline therapy, remissions were achieved in 11 of 29 patients (37.9%), and so clinical cross resistance between idarubicin and other anthracyclines was thought to be partial. The principal adverse effects were gastrointestinal symptoms, alopecia, fever and infection. In the 15 mg/m2 group, there was an increased number of adverse events of WHO's grade 3 or over. The result indicated that Idarubicin is a useful drug for the treatment of acute leukemia, and the clinical optimal dosage estimated was either 10 mg/m2 or 12 mg/m2 once daily for 3 consecutive days. PMID- 8489297 TI - [Early phase II study of Idarubicin combined with cytarabine in acute myelogenous leukemia. Idarubicin Study Group]. AB - An early phase II study of a combination regimen consisting of Idarubicin and Cytarabine was performed in patients with acute myelogenous leukemia. Idarubicin at a dose of 10 mg/m2 or 12 mg/m2 was given by 5-min. iv bolus, once daily for 3 consecutive days and Cytarabine at a dose of 80 mg/m2 was given by 2-hour iv infusion, twice daily for 7 consecutive days. Of 19 patients treated, 17 were evaluable for responses. The patients who showed a response (complete or partial remission) were 4 of 10 (40.0%) in the 10 mg/m2 group, 6 of 7 (85.7%) in the 12 mg/m2 group, and in total, 10 of 17 patients (58.8%), respectively. Analysing relationship between prior chemotherapy and responses, all of 3 patients without pretreatment, 6 of 10 patients (60.0%) in the first relapse, and 1 of 4 patients (25.0%) whose disease had been refractory to induction therapy after relapse responded. Seven of 14 patients (50%) who had received prior anthracycline therapy, showed a response. The principal adverse effects were gastrointestinal symptoms, alopecia, fever and infection, similarly to those observed in Idarubicin single therapy. When combined with Cytarabine, Idarubicin increased the incidence and severity of gastrointestinal symptoms. Considering effectiveness and safety, the clinical optimal dosage of Idarubicin when used concomitantly with Cytarabine was judged to be 12 mg/m2 once daily for 3 consecutive days. PMID- 8489298 TI - [Usefulness of contact thermography for the evaluation of chemotherapeutic effectiveness in breast cancer]. AB - We examined temperature differences between a cancerous breast and its counterpart normal one by contact thermography before and after preoperative chemotherapy, and evaluated the relationship between the changes in the thermograms and response to chemotherapy in six patients with breast cancer. We used the following definitions: 1) delta Tmean: temperature differences between a mean temperature of a cancerous breast and that of the contralateral healthy breast; 2) delta Tmax: temperature differences between a cancer-related hyperthermic area in a breast and the mirror area of contralateral breast; 3) and the thermal patterns in thermogram were estimated by the criteria of Tada et al. In responders the thermograms after chemotherapy indicated an improvement in the hyperthermic vascular pattern (HVP) or hyperthermic area and a decrease of delta Tmean and delta Tmax. In contrast, little or no changes were observed in the thermograms of non-responders. Degrees of changes in thermograms reflected the effectiveness of chemotherapy. Our study showed that chemotherapeutic effectiveness may be better evaluated by combining contact thermography with the present method measuring tumor sizes than by only the present one. PMID- 8489299 TI - [Experimental study on comparative efficacy of hepatic arterial injection of anticancer agent under temporary occlusion of portal vein]. AB - To compare the efficacy of intra-hepatic arterial infusion of anti-cancer drug under temporary occlusion of portal vein, the following two experiments were performed. 1. VX2 tumor cells (about 1 x 10(5) cells) were transplanted through the superior mesenteric vein of the rabbits, after 2 weeks, 4'-0 Tetrahydropyranyl doxorubicin (2 mg/kg, 2 ml) aqueous solution (THP) was administered into hepatic artery of rabbits with metastatic VX2 liver tumor. 2. THP was injected into hepatic artery under temporary occlusion of portal branch of median left lobe with metastatic liver. Then the THP levels of normal liver tissue and tumor of median left lobe and lateral right lobe. The THP levels of tumor under portal occlusion tended to be about 2.63-fold higher than without occlusion. These results suggest that hepatic arterial injection under portal occlusion is more useful to increase the levels of anticancer agents of metastatic liver tumor. PMID- 8489300 TI - [Effect of medroxyprogesterone acetate on antitumor efficacies and side effect of 5-fluorouracil]. AB - Effect of medroxyprogesterone acetate (MPA) on the lethal toxicity, bone marrow toxicity and antitumor efficacies of 5-fluorouracil (5-FU) was examined. The following results were obtained. In aged female ddY mice, the lethal toxicity and body weight loss caused by 5-FU were reduced by MPA. MPA also reduced the bone marrow toxicity of 5-FU in aged female ddY mice. These effects of MPA were not observed in young male ddY mice. Moreover, MPA did not affect the antitumor activity of 5-FU against MPA-insensitive mouse breast carcinoma FM3A, or rather augmented its antitumor activity against MPA-sensitive human breast carcinoma MCF 7. These results indicate that MPA reduces the side effects of 5-FU and augments the antitumor activity of 5-FU in female mice. PMID- 8489301 TI - [Disease-free survival in a patient with squamous cell lung carcinoma following complete response with the combination chemotherapy of cisplatin and etoposide]. AB - Disease-free survival is reported in a patient with non-small cell lung carcinoma successfully treated with the combination chemotherapy of cisplatin and etoposide (CDDP-ETOP). An 80-year-old woman was diagnosed as having squamous cell carcinoma of the lung with bone metastasis. Chest X-ray showed a tumor (64 x 68 mm in size) in the S1/4 segment of the right lobe, and CT scan revealed no apparent metastasis of hilar lymphnode. In March 1989, the patient achieved a complete response (CR) after two courses of CDDP-ETOP therapy, followed by ETOP(100mg) every two weeks and daily UFT (400 mg) for 10 months. Subsequently, a single course of CDDP-ETOP was administered as a consolidation therapy. The patient is alive with no evidence of recurrent disease for 3 years and half after achieving CR. PMID- 8489302 TI - [Effects of combined hormone therapy on the coagulation-fibrinolytic systems in patients with advanced breast cancer]. PMID- 8489303 TI - [Establishment of continuous infusion system via hepatic artery or portal vein of the rat]. PMID- 8489304 TI - [Effect of hepatic arterial injection of liposome-encapsulated cisplatin upon hepatic carcinoma in rats]. PMID- 8489305 TI - [Clinical trial of the systemic chemotherapy for advanced prostatic cancer patients]. PMID- 8489306 TI - [Clinical efficacy of YNK 01 (1-beta-D-arabinofuranosylcytosine-5' stearylphosphate) in patients with polycythemia vera]. PMID- 8489307 TI - Organized medicine in the United States. PMID- 8489308 TI - Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure. AB - OBJECTIVE: This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). SUMMARY BACKGROUND DATA: The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. METHODS: Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16 month intervals. RESULTS: All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. CONCLUSIONS: These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct. PMID- 8489309 TI - Acute pancreatitis of unknown etiology in the elderly. AB - OBJECTIVE: The incidence of acute pancreatitis in the elderly patient is increasing, and a significant number of such patients have no clearly defined etiology of their pancreatitis. To delineate the role of early organ failure versus progressive pancreatic disease in the morbidity and mortality, the authors' experience with patients older than 60 years with acute pancreatitis was reviewed. SUMMARY BACKGROUND DATA: As many as 30%-40% of elderly patients with acute pancreatitis have an unclear etiology and such patients have high rates of early organ failure and death. While some authorities have shown that pre existing disease in these elderly patients did not contribute to subsequent morbidity, others have demonstrated that poor outcome was related to co-existing medical illness. METHODS: Their review of acute pancreatitis in the elderly was grouped into known and unknown etiology patients. Various parameters such as morbidity, mortality and length of stay were then compared between the two groups. Severity of organ failure and acute pancreatitis on admission were both graded and attempts made to correlate this severity with subsequent outcome. RESULTS: Unknown etiology patients had a greater number of Ranson's criteria (3.5 +/- .44 vs. 2.4 +/- .18) (p < 0.02), higher morbidity (48% vs. 22%) (p < 0.05), higher mortality (24% vs. 8.3%), and more SICU days (4.4 +/- 1.3 vs. 1.6 +/- .44) (p < 0.05) when compared with the known etiology group. Duration of symptoms, admission hypotension, and Ranson's criteria were unsuccessful in predicting mortality. Functional status of the various organ systems on admission did predict subsequent mortality. CONCLUSIONS: Elderly patients with acute pancreatitis of unknown etiology present with a more severe disease, have higher morbidity and longer SICU stays, and appear to have greater compromise of organ function. Organ function compromise correlates with mortality and appears more significant than severity of pancreatic disease. Aggressive support of such organ systems may be beneficial in the management of these patients. PMID- 8489310 TI - Experience with mycophenolate mofetil (RS61443) in renal transplantation at a single center. AB - OBJECTIVE: Mycophenolate mofetil (MM) is a new immunosuppressive agent that reversibly inhibits guanine nucleotide synthesis and DNA replication. Its activity is highly selective for T and B lymphocytes. Two open-label multicenter trials of MM in renal transplantation have been performed. This report summarizes the results from one center involved in these two trials. METHODS AND RESULTS: The initial trial of MM was an open-label dose-ranging trial in primary cadaveric renal transplantation. Mycophenolate mofetil was included in the maintenance immunosuppression regimen from the day after transplantation. Of the 21 patients enrolled in this trial, one (5%) was withdrawn for side effects. There was one graft loss due to recurrent renal disease and two patients were withdrawn for difficulty with follow-up. Mean follow-up is 26 months, and patient and graft survival at 2 years are 100 and 95% respectively. The second trial was designed to study the efficacy of mycophenolate in reversing refractory renal allograft rejection. Patients enrolled in the trial had biopsy-proven acute rejection and had previously received at least one course of high-dose corticosteroids and/or OKT3. Of the 26 patients enrolled in this trial, one (4%) was withdrawn for side effects. There were two deaths. Mean follow-up is 20 months, and patient and graft survival at 12 months was 91 and 54%. The incidence of infections in the two groups was 38% and there were no deaths in either group attributable to infection. CONCLUSIONS: The results of these two studies indicate that mycophenolate mofetil could be administered safely to renal allograft recipients for periods up to 2 years. It appears to be effective in reversing acute rejection in a high percentage of patients refractory to other forms of therapy. PMID- 8489311 TI - Soluble HLA class I in the serum of transplant recipients. AB - BACKGROUND: Soluble HLA, Class I (S-HLA-I) has been found in serum, plasma, body fluids, peritoneal dialysates, and urine. S-HLA-I may be a product of membrane shedding, proteolysis, and/or alternate gene splicing. Previous assays to quantitate S-HLA-I were cumbersome, required radioisotope labeling procedures, or the purification of Class I antigen preceding antigen quantitation. The authors developed a solid-phase, enzyme-linked immunoassay that can be used to quantitate S-HLA-I and to study its relevance in transplantation. METHODS: A solid-phase enzyme-linked immunoassay employing monoclonal anti-Class I to catch S-HLA-I present in plasma and peroxidase-labeled monoclonal anti-beta 2-microglobulin (B2M) to quantitate bound S-HLA-I was employed. Values were correlated with rejection and infection episodes. Pre and postoperative determinations were made from the sera of liver, heart, and kidney recipients. Size chromatography was used to compare the molecular weight of S-HLA-I from baseline and peak serum concentrations obtained during rejection episodes (2 liver, 1 heart, 1 kidney), and from 1 kidney recipient with a wound infection. RESULTS: All 9 liver recipients and 12 heart recipients demonstrated a fall in S-HLA-I, or very low initial values, for the first 10 days and then a progressive increase in values substantially above preoperative concentrations. Values from renal recipients were more variable. There were temporary increases in S-HLA-I preceding or during 16 of 20 (80%) biopsy-proven rejections (all reversible), and in 9 of 11 (83%) episodes of infection (bacterial, viral, and fungal). In heart and liver rejection, as well as the wound infection, the sera contained increased S-HLA-I, which was almost all of the same molecular weight (approximately 52,000 daltons). In serum from the one patient with renal rejection, two additional S-HLA-I peaks occurred, one with a molecular weight near 1,000,000 daltons and the second at a molecular weight approximately 11,000 daltons suggesting cellular breakdown of the donor organ. CONCLUSION: In summary, different patterns of S-HLA-I concentrations occur after kidney transplantation. Most liver and heart recipients reached a steady state higher than preoperative levels. Transient increases in S-HLA-I occurred with rejection and infection. In one severe rejection episode, larger and smaller fractions of S-HLA-I were detected and may represent cell membrane breakdown. PMID- 8489312 TI - MHC class II presenting cells are necessary for the induction of intrathymic tolerance. AB - OBJECTIVE: This study determined the form of cellular donor MHC alloantigen necessary for the induction of intrathymic tolerance. BACKGROUND: The authors have achieved indefinite donor-specific tolerance, to a fully MHC-disparate rat heterotopic cardiac allograft, after the pretransplant intrathymic injection of unfractionated donor splenocytes and a single injection of rabbit anti-rat lymphocyte serum (ALS), without subsequent immunosuppression. METHODS: Male 4-12 week-old Buffalo (RT1b) rats underwent an intrathymic injection of either fractionated Lewis (RT1(1)) red blood cells (purified by Ficoll gradient) or T lymphocytes (purified by nylon wool column and plastic adherence), both of which express only MHC class I alloantigens, or B lymphocytes, macrophages, and dendritic cells (purified by plastic adherence) which express both MHC class I and class II alloantigens. At the completion of alloantigen injection the Buffalo recipient rats were given 1 ml of ALS intraperitoneally. Twenty-one days later a heterotopic Lewis heart was transplanted. RESULTS: The intrathymic injection of the fractions of Lewis MHC class I and class II expressing B lymphocytes, macrophages, and dendritic cells induced a donor-specific tolerance that resulted in indefinite Lewis cardiac allograft survival (MST > 125 days) in all recipients without further immunosuppression, whereas groups receiving MHC class I expressing red blood cell or T lymphocyte injections plus ALS rejected Lewis cardiac allografts with a MST of 7.3 and 16.5 days, respectively, thus indicating that the MHC class II expressing cell is necessary for the induction of intrathymic tolerance. Buffalo recipients with a long-term surviving Lewis cardiac allograft, after Lewis MHC class II expressing cells were still able to reject a third-party heterotopic ACI (RT1a) cardiac allograft in normal time (MST = 7.0 days), but did not reject a second Lewis cardiac allograft (MST > 100 days). Additionally, the intrathymic injection of MHC class II expressing cells resulted in decreased interleukin-2 (IL-2) production and an 80% decrease in in vitro donor-specific cell mediated cytotoxicity, whereas the cytolytic response to a third party was unaltered. CONCLUSION: Donor MHC class II, and not class I, expressing cells are the cells in donor splenocytes, injected intrathymically, responsible for the development of donor-specific allograft tolerance. PMID- 8489313 TI - Development of a hybrid bioartificial liver. AB - OBJECTIVE: The authors developed an extracorporeal liver support system and tested its efficacy in experimental animals with liver failure. The first clinical use of this system to treat a patient with liver failure is reported. SUMMARY BACKGROUND DATA: Multiple attempts have been made, ranging from plasma exchange to use of charcoal columns, to develop liver support systems for treating patients with acute severe liver failure. None of these systems has achieved wide clinical use. There is a need for providing liver support as a "bridge" to transplantation and for treating patients with potentially reversible liver dysfunction. METHODS: A hybrid liver support system has been developed consisting of plasma perfusion through a charcoal column and a porous hollow fiber module inoculated with 5 x 10(9) matrix-attached hepatocytes. The system was tested in dogs with ischemic liver failure (n = 7) who underwent plasmapheresis; a control group (n = 6) underwent charcoal perfusion alone. A patient with liver failure was treated with this hybrid system. RESULTS: After 6 hours of hybrid liver support treatment, animals had significantly decreased serum ammonia and lactate levels, increased glucose level, normal prothrombin time, and increased systolic blood pressure compared with controls treated with charcoal perfusion alone. Use of the system to treat a patient was well tolerated with evidence of clinical improvement. CONCLUSIONS: Plasma perfusion through a system consisting of a charcoal column and matrix-attached porcine hepatocytes had significant beneficial effects in animals with liver failure and was well tolerated by a patient with liver failure. PMID- 8489314 TI - Successful transplantation of marginally acceptable thoracic organs. AB - OBJECTIVE: This study evaluates the efficacy of personally inspecting marginal thoracic organ donors to expand the donor pool. SUMMARY BACKGROUND DATA: The present donor criteria for heart and lung transplantation are very strict and result in exclusion of many potential thoracic organ donors. Due to a limited donor pool, 20-30% of patients die waiting for transplantation. METHODS: The authors have performed a prospective study of personally inspecting marginal donor organs that previously would have been rejected by standard donor criteria. RESULTS: Fourteen marginal hearts and eleven marginal lungs were inspected. All 14 marginal hearts and 10 of the marginal lungs were transplanted. All cardiac transplant patients did well. The mean ejection fraction of the donor hearts preoperatively was 39 +/- 11% (range 15-50%). Postoperatively, the ejection fraction of the donor hearts improved significantly to 55 +/- 3% (p < 0.002). Nine of the ten lung transplant patients did well and were operative survivors. Our donor pool expanded by 36% over the study period. CONCLUSIONS: The present donor criteria for heart and lung transplantation are too strict. Personal inspection of marginal thoracic donor organs will help to maximize donor utilization. PMID- 8489315 TI - Infections caused by halophilic marine Vibrio bacteria. AB - OBJECTIVE: The authors reviewed patients who developed sepsis or soft tissue infections caused by marine Vibrio bacteria in Florida. SUMMARY BACKGROUND DATA: Marine Vibrio bacteria are the most common bacteria found in seawater. They are concentrated in marine animals that feed by filtration such as oysters and clams. These bacteria can cause gastroenteritis, sepsis, cellulitis leading to necrotizing soft tissue infection after exposure to seawater or consumption of raw seafood. METHODS: The authors received 182 systemic infections that occurred in Florida between January 1, 1979, and December 31, 1991, which were treated by the authors or were reported to the Florida Department of Health and Rehabilitative Services. Patients were divided into two groups depending on whether they presented with primary bacteremia or soft tissue infection. RESULTS: Seventy-one patients had been exposed to these bacteria by eating raw seafood, 94 had direct exposure to seawater, and exposure was uncertain in 27 patients. Vibrio species were cultured from the blood of 103 patients and from wounds or soft tissues of 113. An additional 5 patients had cellulitis but bacteria were not cultured from these sites. In patients in whom it could be determined, 93 had primary soft tissue infections and 82 had primary bacteremia. Twenty-four patients had necrotizing soft tissue infections and required surgical debridement. Three of these 24 patients required amputation. Thirty-seven (20.3%) patients died. Severe liver disease occurred in 54 patients and 25 of these patients died. CONCLUSIONS: Marine Vibrio bacteria can cause sepsis and soft tissue infections, especially in individuals with severe liver disease and other chronic illnesses such as diabetes mellitus. The authors believe all individuals, especially those with systemic illness, should be warned against eating raw seafood. PMID- 8489316 TI - Management of major biliary complications after laparoscopic cholecystectomy. AB - OBJECTIVE: A total of 50 major bile duct injuries after laparoscopic cholecystectomy were managed by the Duke University Hepatobiliary Service from 1990-1992. The management of these complex cases is reviewed. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy is the preferred method for removing the gallbladder. Bile duct injury is the most feared complication of the new procedure. METHODS: Review of videotapes, pathology, and management of the original operations were reviewed retrospectively, and the injuries categorized. Major biliary injury was defined as a recognized disruption of any part of the major extrahepatic biliary system. Biliary leakage was defined as a clinically significant biliary fistula in the absence of major biliary injury, i.e., with an intact extrahepatic biliary system. RESULTS: Thirty-eight injuries were major biliary ductal injuries and 12 patients had simple biliary leakage. Twenty-four patients had the classic type injury or some variant of the classic injury. A standard treatment approach was developed which consisted of ERCP for diagnosis, preoperative PTC with the placement of stents, CT drainage immediately after the PTC for drainage of biliary ascites, and usually Roux-en-Y hepaticojejunostomy with placement of O-rings for future biliary access if necessary. Major ductal injuries were high in the biliary system involving multiple ducts in 31 of the 38 patients. Re-operation was required in 5 of the 38 patients with particularly complex problems. CONCLUSIONS: Successful management of bile duct injury after laparoscopic cholecystectomy requires careful understanding of the mechanisms, considerable preoperative assessment by experts, and a multidisciplinary approach. PMID- 8489317 TI - Laparoscopically harvested omental free flap to cover a large soft tissue defect. AB - OBJECTIVE: The omentum has been a very important tool in the armamentarium of the reconstructive surgeon. It has lost much of its value because of the morbidity associated with laparotomy. Laparoscopic surgery has become a popular technique and allows operations to be performed with minimal morbidity. The possibility of harvesting the omental free flap with the laparoscope and its use in reconstructive surgery has been demonstrated. SUMMARY BACKGROUND DATA: Since the first laparoscopic cholecystectomy was performed, many surgeons have learned the procedure. Other surgical specialties have also benefited from this technique. The omentum provides a large amount of vascularized tissue and excellent wound coverage. It can be transferred as a pedicle flap, or as a free flap, using microvascular technique. METHODS: The procedure was developed and refined in an animal model. One team harvested the omentum with laparoscopic assistance, while the other team prepared the recipient vessels. After completion of the microvascular transfer, the dogs were observed for 14 days. At that time, the omental tissue was examined for gross and histologic changes. A clinical case is also presented. RESULTS: Gross and microscopic studies documented the viability of this approach. The patient tolerated the procedure well and had an unremarkable postoperative course. CONCLUSIONS: Experimental and clinical evidence shows that the omentum can be successfully harvested as a free flap using laparoscopic assistance. This technique may prove to be of clinical significance and very useful for reconstructive surgery with less morbidity. PMID- 8489318 TI - Endoscopic management of peptic ulcer disease. AB - OBJECTIVE: This article reviews the authors' experience with endoscopic management of duodenal ulcer and ulcers occurring after a previous drainage procedure. SUMMARY BACKGROUND DATA: Patients with complications of duodenal ulcer and ulcers occurring after a previous drainage procedure still require surgical management. Virtually all operations for duodenal ulcer include some form of vagotomy. American surgeons in academic centers prefer highly selective vagotomy in suitable candidates. Video-directed laparoscopic and thoracoscopic operations have been done for all complications of duodenal ulcer except for acute hemorrhage. METHODS: The authors have performed laparoscopic operation on eight patients with intractable chronic duodenal ulcer, seven patients with gastroesophageal reflux disease combined with duodenal ulcer, one patient with chronic duodenal ulcer and gastric outlet obstruction, and one patient with acute perforation. Operations performed included omentopexy, anterior seromyotomy plus post truncal vagotomy, and highly selective vagotomy. Seven patients had a simultaneous Nissen fundoplication; and the patient with obstruction underwent concomitant pyloroplasty and vagotomy. Six patients with intestinal ulcers occurring after a previous drainage procedure were treated with thoracoscopic vagotomy. Techniques used are shown. RESULTS: There has been one recurrent ulcer in the laparoscopic group after anterior seromyotomy plus posterior truncal vagotomy. The patient treated by omentopexy for duodenal perforation recovered gastrointestinal function promptly with no further difficulty, but eventually died of primary medical disease. Patients undergoing thoracoscopic vagotomy have all become asymptomatic. Postoperative hospital stay after highly selective vagotomy, anterior seromyotomy plus posterior truncal vagotomy, or thoracoscopic vagotomy was 1-5 days. CONCLUSIONS: Laparoscopic management of duodenal ulcers is feasible. Larger numbers of patients with longer follow-up are essential. Ulcers occurring after a drainage procedure deserve thoracoscopic vagotomy. PMID- 8489319 TI - A prospective analysis of diagnostic laparoscopy in trauma. AB - OBJECTIVE: This study was performed to assess current and potential future application for laparoscopy (DL) in the diagnosis of penetrating and blunt injuries. Efficacy, safety, and cost analyses were performed. SUMMARY BACKGROUND DATA: Diagnostic peritoneal lavage (DPL) and computed tomography (CT) have been the mainstays in recent years for diagnosis of equivocal nontherapeutic laparotomy, whereas CT is not helpful for the vast majority of penetrating wounds. DL may be a useful adjunct to fill in these gaps. METHODS: Hemodynamically stable patients with equivocal evidence of intraabdominal injury were prospectively entered into the protocol. DL was performed under general anesthesia; patients with wounds penetrating the peritoneum or blunt injury with significant organ injury underwent laparotomy. RESULTS: Over 19 months, 182 patients (55% stab, 36% GSW, 9% blunt) were studied. No peritoneal penetration was found at DL in 55% of penetrating wounds with 66% of the remainder having therapeutic laparotomy, 17% nontherapeutic laparotomy, and 17% negative laparotomy. Therapeutic laparotomy was performed in 53% of blunt injuries after DL. Tension pneumothorax occurred in one patient and one had an iatrogenic small bowel injury. Charges for DL were $3,325 per patient compared with $3,320 for a similar group undergoing negative laparotomy before this protocol. CONCLUSIONS: DL is a safe modality for trauma. With current technology, DL is most efficacious for evaluation of equivocal penetrating wounds. Significant cost savings would be gained by performance under local anesthesia. Development of miniaturized optics, bowel clamps, retractors, and stapling devices will reduce overall costs and permit some therapeutic applications for laparoscopy in trauma management. PMID- 8489320 TI - Thoracoscopic surgery for diseases of the lung and pleura. Effectiveness, changing indications, and limitations. AB - OBJECTIVE: This study compared the results of video-assisted thoracic surgery (VATS) with thoracoscopic surgery (TS) for diseases of the lung and pleura. SUMMARY BACKGROUND DATA: No studies exist that compare the capabilities of VATS with advanced video systems and instrumentation to that of TS which has been done for 80 years. METHODS: A retrospective study was done comparing the effectiveness, indications, complications, and limitations of TS and VATS done for four categories of pleural disease: 1) pleural fluid problems, 2) diffuse lung disease, 3) lung masses, and 4) pneumothorax. The TS period was 1981-1990. The VATS period was 1991-1992. RESULTS: Eighty-nine consecutive TS cases and 64 consecutive VATS cases were reviewed. TS for resolution of pleural fluid problem was successful in 29 of 34 patients (85%), and VATS was successful in 18 of 20 (90%). Diffuse lung disease was diagnosed by TS using a cup biopsy on end-stage patients in respiratory failure. Since 1991 the diagnosis has been made with VATS using stapled wedge excisions on ambulatory patients. Surgical mortality decreased from 33% (10 of 30) to 9% (1 of 11) and the postoperative stay from 16.6 +/- 2.4 days to 8.2 +/- 2.2 days. Lung masses were diagnosed entirely by incisional biopsies using TS. Diagnosis was made in 83% and postoperative stay was 5.3 +/- 1.0 day. VATS allowed excisional biopsies permitting diagnosis in 100% with a postoperative stay of 3.0 +/- 0.2 days (p = 0.05). However, 20% required conversion to thoracotomy to locate the subpleural mass. TS was performed for spontaneous pneumothorax in only 26% (5 of 19) of the total pneumothorax cases, whereas, VATS was used for spontaneous pneumothorax in 67% (12 of 18). CONCLUSION: VATS has continued the effectiveness of TS for treating pleural fluid problems, has resulted in earlier surgical diagnostic intervention in diffuse lung disease and earlier therapeutic intervention in primary pneumothorax states, and has markedly expanded the safety, efficacy and indications for lung mass biopsy. PMID- 8489321 TI - The staged celiotomy for trauma. Issues in unpacking and reconstruction. AB - OBJECTIVE: This article describes the important clinical events and decisions surrounding the reconstruction/unpacking portion of the staged celiotomy for trauma. METHODS: Of 13,817 consecutive trauma admissions, 1175 received trauma celiotomies. Of these, 107 patients (9.1%) underwent staged celiotomy with abdominal packing. The authors examined medical records to identify and characterize: (1) indications and timing of reconstruction, (2) criteria for emergency return to the operating room, (3) complications after reconstruction, and (4) abdominal compartment syndrome (ACS). RESULTS: Fifty-eight patients (54.2%) survived to reconstruction, 43 (74.1%) survived to discharge; 9 patients (15.5%) were returned to the operating room for bleeding; 13 patients required multiple packing procedures. There were 117 complications; 8 patients had positive blood cultures, abdominal abscesses developed in 6 patients, and ACS developed in 16 patients. CONCLUSIONS: 1. Reconstruction should occur after temperature, coagulopathy, and acidosis are corrected, usually within 36 hours after the damage control procedure. 2. Emergent reoperation should occur in any normothermic patient with unabated bleeding (greater than 2 U packed cells/hr). 3. ACS occurs in 15% of patients and is characterized by high peak inspiratory pressure, CO2 retention, and oliguria. Lethal reperfusion syndrome is common but preventable. PMID- 8489322 TI - Brain metabolism in teenagers with attention-deficit hyperactivity disorder. AB - OBJECTIVES: We sought to obtain and compare values of cerebral glucose metabolism in normal minors and minors with Attention Deficit Hyperactivity Disorder (ADHD). We also sought to confirm our earlier findings of reduced brain metabolism in adults with ADHD, and to examine whether these results might be diagnostically useful. DESIGN: Case-control study. SETTING: Adolescents were recruited to National Institutes of Health Clinical Center/Research Facility through advertisement at local high schools and ADHD organizations. PATIENTS: Subjects were 10 normal adolescents and 10 adolescents with ADHD diagnosed with structured interviews using DSM-III-R criteria. MAIN OUTCOME MEASURES: Positron emission tomography and fludeoxyglucose F18 were used to study cerebral glucose metabolism in minors while they performed an auditory-attention task. RESULTS: Global or absolute measures of metabolism did not statistically differ between groups, although hyperactive girls had a 17.6% lower absolute brain metabolism than normal girls. As compared with the values for the controls, normalized glucose metabolism was significantly reduced in six of 60 specific regions of the brain, including an area of the left anterior frontal lobe (P < .05). Lower metabolism in that specific region of the left anterior frontal lobe was significantly inversely correlated with measures of symptom severity (P < .001-.009, r = -.56 to -.67). CONCLUSIONS: Global or absolute measures of metabolism using positron emission tomography and fludeoxyglucose F18 did not statistically differentiate between normal adolescents with ADHD. Positron emission tomography scans can be performed and are well tolerated by normal teenagers and teenagers with ADHD. The feasibility of normal minors participating in research involving radiation was established. PMID- 8489323 TI - An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET. AB - OBJECTIVES: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. DESIGN: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. PATIENTS: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. RESULTS: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. CONCLUSIONS: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections. PMID- 8489324 TI - Evidence of subtypes of Alzheimer's disease and implications for etiology. AB - OBJECTIVE: Because age of onset does not reliably define two subtypes of Alzheimer's disease, classification based on the severity of neuronal degeneration was tested. DESIGN: Numbers of extracellular tangles and pyramidal neurons in the hippocampus were used to group patients. PATIENTS: The study population consisted of 46 elderly patients satisfying DSM-III criteria for dementia and NINCDS-ADRDA criteria for definite Alzheimer's disease after death. RESULTS: Univariate logistic regression analysis showed the numbers of neurofibrillary tangles and pyramidal neurons and the duration of dementia were significantly associated with grouping based on the presence of abundant extracellular tangles. Ninety-one percent of patients were correctly classified as compared with 85% correctly classified by age of onset data. Odds ratios showed that increasing numbers of neurofibrillary tangles predicted greater severity of neuronal loss. CONCLUSION: The results of the study indicate the importance of neurofibrillary degeneration, not the deposition of amyloid, in the pathogenesis of Alzheimer's disease. They support a classification of Alzheimer's disease related more closely to the severity of neurofibrillary degeneration than to age at onset. PMID- 8489325 TI - Brain morphology, dopamine, and eye-tracking abnormalities in first-episode schizophrenia. Prevalence and clinical correlates. AB - OBJECTIVE: To characterize the pathophysiology of schizophrenia and to identify biologic markers in first-episode patients with no or little prior treatment exposure. DESIGN: Prospective study of an inception cohort. SETTING: Psychiatric division of an academic medical center with a suburban metropolitan catchment area. PATIENTS: 70 patients in their first episode of schizophrenia (77%) or schizoaffective disorder (23%) with no (70%) or limited prior neuroleptic exposure (30%), and 50 healthy volunteer control subjects. ASSESSMENT MEASURES: Demographic and clinical evaluations of natural history and psychopathology; methylphenidate hydrochloride and apomorphine hydrochloride stimulation tests as measures of central nervous system dopamine activity; brain magnetic resonance imaging; eye-tracking examinations. RESULTS: Preliminary analyses demonstrate that pathobiologic features previously identified in heterogeneous and primarily chronically ill patients are also present in subgroups during their first episode. These include psychotogenic response to methylphenidate (59%), abnormal growth hormone (GH) secretion (50%), abnormal brain morphology (31%), and eye tracking dysfunction (51%). An association of pathobiologic variables with increased symptom severity and earlier age of onset was observed but not statistically significant. The strongest associations among biologic variables were for the following: GH secretion and psychotogenic response to methylphenidate, which may reflect increased dopamine agonist neural activity; decreased GH response to apomorphine and third-ventricle enlargement, which may represent a neuropathologic correlate of anterior pituitary abnormalities; and morphologic abnormalities of the medial temporal lobe and third ventricle were associated with normal eye tracking, suggesting that these pathobiologic features are mediated by distinct processes. CONCLUSIONS: These phenomena appear to be a consequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. It remains to be determined if these biologic phenomena will remain stable over time or change with disease progression. A companion article examines the clinical significance of these findings. PMID- 8489326 TI - Efficacy of phenelzine and haloperidol in borderline personality disorder. AB - OBJECTIVE: To compare the efficacy of a neuroleptic (haloperidol) to a monoamine oxidase inhibitor antidepressant (phenelzine sulfate) against the affective, cognitive, and impulsive-aggressive symptoms of criteria-defined borderline inpatients in an effort to dissect apart affective and schizotypal symptom patterns or subtypes using medication response. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient unit of a tertiary care university psychiatric hospital serving a large public catchment area. PATIENTS: One hundred eight consecutively admitted borderline inpatients defined by Gunderson's Diagnostic Interview for Borderline Patients and DSM-III-R criteria, randomly assigned to 38 phenelzine, 36 haloperidol, and 34 placebo trials. INTERVENTIONS: Following 1 week free of medication, haloperidol (average dose, 4 mg/d), phenelzine sulfate (average dose, 60 mg/d), or placebo were given for 5 weeks with weekly symptom ratings and plasma drug level determinations. MAIN OUTCOME MEASURES: Efficacy was measured on depression (Hamilton Rating Scale, Beck Depression Inventory), global severity (Global Assessment Scale, Symptom Checklist-90 items [SCL-90]), anxiety, anger-hostility (SCL-90, Inpatient Multidimensional Psychiatric Scale [IMPS], Buss-Durkee Hostility Inventory), psychoticism (Schizotypal Symptom Inventory, SCL-90, IMPS), impulsivity (Ward Scale, Barratt Impulsiveness Scale, Self-Report Test of Impulse Control), and borderline psychotherapy (Borderline Syndrome Index). RESULTS: Three-way comparisons between groups indicated superior efficacy for phenelzine, followed by placebo and haloperidol on measures of depression, borderline psychopathologic symptoms, and anxiety. Pairwise comparisons between medication and placebo revealed significant efficacy for phenelzine against anger and hostility but no efficacy against atypical depression or hysteroid dysphoria. We were unable to replicate prior reports of efficacy for the neuroleptic. CONCLUSIONS: Pharmacologic dissection of borderline personality disorder patients into affective and schizotypal subtypes could not be demonstrated. PMID- 8489327 TI - A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. AB - OBJECTIVE: To directly compare the efficacy of lithium carbonate and liothyronine sodium (triiodothyronine) in the augmentation of therapeutic response in antidepressant nonresponders. DESIGN: A randomized, double-blind, placebo controlled study of 2 weeks' duration. SETTING: The Mood Disorders Program, Clarke Institute of Psychiatry and the University of Toronto, Ontario. PATIENTS: Fifty outpatients, males and females, with unipolar, nonpsychotic major depression who had failed to respond to treatment with desipramine hydrochloride or imipramine hydrochloride. RESULTS: Both liothyronine and lithium were more effective than placebo in reducing scores on the Hamilton Rating Scale for Depression. However, the antidepressant augmenting effect of these two compounds did not differ from each other. When response was defined as a 50% or more reduction in the Hamilton Rating Scale for Depression scores and a final score less than 10, we found that 10 of 17 subjects responded to liothyronine, nine of 17 responded to lithium and three of 16 responded to placebo. CONCLUSIONS: Our study suggests that both lithium and liothyronine may be considered as alternatives in augmenting antidepressant response in patients who do not respond to treatment with a tricyclic antidepressant. PMID- 8489328 TI - Dissociation between pituitary and adrenal suppression to dexamethasone in depression. AB - OBJECTIVE: To determine if corticotroph nonsuppression, as reflected by beta endorphin nonsuppression, occurs before cortisol nonsuppression (defined as a cortisol level of > 140 nmol/L) when examining multiple time points in a day. SETTING: The General Medical Clinical Research Center and Inpatient Depression Research Unit, Ann Arbor, Mich. DESIGN: Multiple blood samples were obtained through an intravenous catheter around the time points of 8 AM, noon, and 4 PM and assayed for beta-endorphin and cortisol. PATIENTS: Patients meeting Research Diagnostic Criteria for the diagnosis of major depressive disorder, primary and simple. A total of 73 subjects, both inpatients and outpatients, were studied. INTERVENTION: Samples were obtained both at baseline and 1 day after administration of 1 mg of dexamethasone at 11:30 PM. MEASUREMENTS AND RESULTS: Overall 39 patients (53%) demonstrated beta-endorphin nonsuppression after administration of dexamethasone at any of the three time points, while only eight patients (11%) demonstrated cortisol nonsuppression at any of these time points. Cortisol nonsuppression, but not beta-endorphin nonsuppression, was associated with lower concentrations of dexamethasone in plasma. Baseline cortisol and menopausal status were significantly associated with beta-endorphin nonsuppression in women. PMID- 8489329 TI - The definition of remission and its impact on the length of a depressive episode. PMID- 8489330 TI - Seasonal effects on platelet 5-HT content in patients with OCD and controls. PMID- 8489331 TI - The Human Genome Project. History, goals, and progress to date. AB - This article presents an overview of the Human Genome Project. The goals of the program are outlined; the genetic, physical, and DNA sequence maps that will be its products are defined; the brief origins of the project are traced; the management structure of the US Human Genome Project, in which the Department of Energy and the National Institutes of Health participate as partners, is outlined; international dimensions are discussed; the excellent progress to date with respect to each of the eight scientific goals is reported; and the projected impact of the project on biology and medicine is discussed. PMID- 8489332 TI - Ethics and the Human Genome Project. AB - This article provides an overview of ethical issues in genetic testing and screening as they are currently considered in relationship to the Human Genome Project. Previous landmark reports and policy recommendations on genetic testing and screening are briefly described. The goals and research interests of the joint National Institutes of Health/Department of Energy Ethical, Legal, and Social Working Group of the Human Genome Project are outlined. To provide an example of one method by which ethical issues in genetics may be addressed, the ethical framework and practical aspects of a clinical ethics research project at the University of Washington, Seattle, are described. Finally, future directions for the study of ethical and social issues related to genetic testing and screening programs are suggested. PMID- 8489333 TI - Molecular genetics. Introduction. AB - While sharing the same techniques as the field at large, diagnostic molecular genetics is unique among the subdisciplines of molecular pathology in many of its aspects, from sample collection to ethical implications of the test results obtained. Yet, despite its many challenges, this branch of DNA diagnostics has already pervaded the practice of medical genetics to an extent unmatched in any other clinical specialty. Genetic disease also presents the most immediately obvious opportunities for extension from DNA-based diagnosis to DNA-based therapy. PMID- 8489334 TI - Detection and quantitation of human immunodeficiency virus type 1 using molecular DNA/RNA technology. AB - The direct detection and quantitation of human immunodeficiency virus type 1 are becoming increasingly important for diagnosis and viral load determinations in human immunodeficiency virus type 1 infection. Traditional molecular-based assays such as Southern, Northern, and in situ hybridization have had limited application in this area due to the relatively low number of proviral copies per cell, the low percentage of infected cells, and transcriptional dormancy in many of the infected cells. Recent technological advances in polymerase chain reaction assays promise a number of useful applications in the clinical research and clinical laboratory setting. PMID- 8489335 TI - In situ hybridization. A research technique or routine diagnostic test? AB - In situ hybridization is the molecular method for localizing nucleic acid targets in the context of histomorphology. As such, it has tremendous potential application in research and diagnostic pathology. This essay attempts to briefly review the in situ method and to clarify its position as an emerging clinically useful technology. PMID- 8489336 TI - Analysis of HLA class II polymorphism using polymerase chain reaction. AB - A simple, rapid, and precise method of typing HLA class II polymorphism would be valuable in the areas of disease susceptibility, tissue transplantation, individual identification, and anthropological genetics. Herein, we describe a method of analyzing class II sequence polymorphism based on polymerase chain reaction (PCR) amplification and hybridization with oligonucleotide probes. Many more DNA-defined alleles at the class II loci have been identified than can be distinguished by conventional serologic typing. Consequently, matching transplant donors and recipients by PCR/oligonucleotide typing should reduce graft rejection and graft-vs-host disease. Also, the ability to identify alleles conferring genetic predisposition to specific diseases (eg, insulin-dependent diabetes mellitus) is significantly enhanced by distinguishing the many alleles or "subtypes" within a serologic type (eg, DR4). One valuable property of sequence based HLA typing strategies, like oligonucleotide probe hybridization, is that they reveal how and where two alleles differ, not simply that they can be operationally distinguished. The nature and location of HLA polymorphisms appears to be critical in disease association studies and are important in tissue typing for transplantation. New alleles at the DRB1, DPB1, and DQB1 loci are likely to be identified as this technology is applied to more and more samples, particularly in nonwhite ethnic groups. A new allele is uncovered as an unusual pattern of probe binding and then confirmed by sequencing. This pattern is observed because class II polymorphism is localized to specific regions and virtually all "new" alleles represent "shuffled" combinations of polymorphic sequences found in previously known alleles. Since these polymorphisms are in the region of probe binding, these new alleles can be detected without increasing the probe panel. Obviously, any new allele with a new polymorphic sequence in a region for which typing probes are not available would not be revealed by oligonucleotide typing. With the PCR primers and probes described here, 7 DQ alpha 1 alleles, 15 DQ beta 1 alleles, 18 DPB1 alleles, and 32 DRB1 alleles are distinguished. Additional primers and/or probes can, of course, increase the allelic discrimination of PCR/oligonucleotide probe typing. These horseradish peroxidase-labeled oligonucleotide probes are stable (> 2 years when stored at 4 degrees C) and the typing system is simple and robust. Although this dot blot/oligonucleotide hybridization procedure is a powerful and precise method of HLA class II typing, the complexity of the procedure increases as the number of probes required for analysis increases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8489337 TI - Forensic DNA testing. AB - Forensic deoxyribonucleic acid (DNA) testing has revolutionized criminal investigations. Deoxyribonucleic acid testing is superseding traditional serologic testing due to its discriminatory power, universal application to biologic materials, and resistance to environmental insults, among other advantages. Its acceptance is becoming commonplace, and it is being put into widespread use. Forensic DNA testing technology and its application is continuing to evolve. PMID- 8489338 TI - Lack of effect of prophylactic aerosolized pentamidine on the detection of Pneumocystis carinii in induced sputum or bronchoalveolar lavage specimens. AB - Two independent studies were undertaken to determine the effect of prophylactic treatment with aerosolized pentamidine on the laboratory diagnosis of Pneumocystis carinii pneumonia in individuals at risk for or with the acquired immunodeficiency syndrome. The first study was a retrospective analysis to determine the effect of prophylactic treatment with aerosolized pentamidine on the diagnostic yield and sensitivity of detection of P carinii in induced sputum specimens. The results of examinations of 110 induced sputum specimens from patients who had not received aerosolized pentamidine were compared with the findings in 57 specimens from patients who had. There was no statistically significant difference between the two groups for the diagnostic yield in induced sputum specimens (48% vs 47%) or in bronchoalveolar lavage fluid specimens subsequently obtained from patients with nondiagnostic induced sputum examinations (33% vs 37%). The sensitivity of induced sputum specimens for identifying P carinii was 76% to 78% for patients who had not received aerosolized pentamidine and 71% to 75% for patients who had received the drug. The second study was a prospective comparison of 118 bronchoalveolar lavage fluid specimens to determine the effect of prophylactic treatment with aerosolized pentamidine on the number of organisms present. One hundred eighteen bronchoalveolar lavage fluid specimens were quantitatively examined and scored according to the number of clumps of P carinii present. No statistically significant difference was seen in the number of clumps of P carinii found in specimens from patients who had received aerosolized pentamidine vs the number of clumps found in specimens from patients who had not. In conclusion, prophylactic treatment with aerosolized pentamidine had no effect on (1) the diagnostic yield and sensitivity of detection of P carinii in induced sputum specimens or (2) the number of organisms detected in bronchoalveolar lavage fluid specimens obtained from individuals at risk for or with the acquired immunodeficiency syndrome. PMID- 8489339 TI - Plasma cell hyperplasia and monoclonal paraproteinemia in human immunodeficiency virus-infected patients. AB - Twenty-seven bone marrow aspirates and biopsy specimens from human immunodeficiency virus-positive patients with plasmacytosis were analyzed to identify the pathologic correlates of polyclonal and monoclonal hypergammaglobulinemia in these patients, to compare the results with another random group of similar human immunodeficiency virus patients with plasmacytosis who did not have serum protein electrophoresis, and to evaluate the significance of the presence of monoclonal proteins in a few patients. Serum protein electrophoresis and immunoelectrophoresis and/or immunofixation electrophoresis revealed monoclonal spikes in five of 18 patients tested. The remaining patients with an abnormal serum protein electrophoresis showed a polyclonal hypergammaglobulinemia. Immunohistochemical stains for kappa and lambda light chains were performed in the bone marrow specimens to determine the presence and/or absence of light-chain preponderance or monoclonality. The percentage of plasma cells varied from 5% to 30% and atypical plasma cells from 1% to 20%. Plasma cell aggregates were present in every case, but variable in number and generally small. In all these cases, including those with monoclonal spikes, plasma cells expressed lambda and kappa light chains with approximately equal intensity. There were no identifiable morphologic differences between the two groups of patients. The paraproteins observed in these patients are likely a reflection of B-cell overactivation. It is important to be aware of this peculiar subset of human immunodeficiency virus-infected patients to avoid an erroneous diagnosis of plasma cell dyscrasia. PMID- 8489340 TI - The use of a commercially available enzyme immunoassay for the detection of Clostridium difficile toxin A. AB - A commercially available enzyme immunoassay (EIA) for the detection of Clostridium difficile toxin A (Premier Toxin A EIA, Meridian Diagnostics, Cincinnati, Ohio) was compared with tissue culture cytotoxicity assay, enterotoxigenic culture, and latex agglutination test for the laboratory diagnosis of C difficile-associated disease. When evaluated for detection of C difficile-associated disease using clinical specimens, EIA was the most sensitive (83.1%) and tissue culture cytotoxicity assay was the most specific test with EIA, tissue culture cytotoxicity assay and enterotoxigenic culture having similar correlation values (96.6, 96.1, 94.0%, respectively). The latex agglutination test was not as accurate (89.7% correlation) as the other three tests due mainly to its poor sensitivity (47.9%). The EIA is a rapid, easy-to-use alternative to tissue culture cytotoxicity assay for detection of C difficile-associated disease. PMID- 8489341 TI - Detection and isolation of Mycoplasma fermentans from urine of human immunodeficiency virus type 1-infected patients. AB - Mycoplasma fermentans (incognitus strain) has been linked with acquired immunodeficiency syndrome-associated nephropathy. Ten (23%) of 43 urine sediment specimens from 40 human immunodeficiency virus (HIV)-positive patients at different stages of acquired immunodeficiency syndrome disease tested positive in the polymerase chain reaction using a primer pair found in the insertion sequences specific to M fermentans. Mycoplasma fermentans was isolated from two HIV-positive patients' urine sediment specimens and on a repeated basis from one. All three culture-positive urine sediment specimens tested positive in the polymerase chain reaction. Fifty urine sediment specimens from age-matched HIV negative healthy controls tested negative for M fermentans by polymerase chain reaction. Mycoplasma fermentans was not isolated from any of the control urine sediment specimens. Our results show a high prevalence of M fermentans in urine sediment specimens from HIV-positive patients but not from urine sediment specimens of HIV-negative healthy controls. PMID- 8489342 TI - Concurrent isolation of Candida krusei and Candida tropicalis from multiple blood cultures in a patient with acute leukemia. AB - Reports of the concurrent isolation of more than one non-albicans species of Candida from blood cultures of immunocompromised patients with disseminated candidiasis are extremely infrequent. We report on the isolation of Candida krusei and Candida tropicalis from 17 blood cultures that were taken from a 67 year-old white man with a diagnosis of acute biphenotypic leukemia during a 2 week period of hospitalization for induction chemotherapy. Despite receiving high dose amphotericin B throughout this period, the status of the patient worsened, and he experienced pancytopenia, hypernatremia, azotemia, and disseminated intravascular coagulation, which led to his death. Candida krusei and C tropicalis were isolated concurrently from 10 of the 17 blood cultures, while C krusei was the single isolate in three cultures and C tropicalis was isolated alone in four cultures. Each species manifested markedly different colonial morphological features. This case report serves to emphasize to microbiologists that they must exercise extreme suspicion when non-albicans species of Candida are isolated singly or concurrently from blood cultures in neutropenic patients, given the increasing clinical significance of these yeasts. PMID- 8489343 TI - Neutropenic enterocolitis. Two unusual cases with review of the literature. AB - Cases of neutropenic enterocolitis associated with Clostridium septicum infection have been reported with increasing frequency in the past decade. We report two such cases involving unusual hosts and briefly discuss possible pathogenetic mechanisms such as ischemia, mucosal damage related to chemotherapy and neutropenia, and immunosuppression. One case involved a young man with chronic Epstein-Barr infection who developed extensive gas gangrene of the right side of his trunk and thigh and who died within 12 hours of presentation to the emergency department. Diagnosis was only made at postmortem examination. The second, middle aged patient was admitted with an acute abdomen shortly after he completed chemotherapy for pleural mesothelioma. A right hemicolectomy was performed, but the patient developed antibiotic-associated pseudomembranous colitis and died. These cases indicate that neutropenic enterocolitis may arise in a variety of underlying conditions and that prompt diagnosis and therapy will be required to salvage more patients with this disorder. PMID- 8489344 TI - Granulocyte aggregation is edetic acid and temperature dependent. AB - Nineteen cases of leukocyte agglutination were observed in the last 6 years, while performing routine blood cell counts with an autoanalyzer (Technicon H6000). The phenomenon occurred only in edetic acid-anticoagulated samples and only at room temperature. Leukocyte aggregation could be reproduced by incubating patient serum samples or edetic acid-plasma with whole blood from ABO-compatible healthy control subjects. When patient serum samples or plasma samples were first preincubated with anti-IgM serum and then mixed with normal blood, leuko agglutinates were not observed, suggesting that a plasma factor, probably an IgM, was responsible for the phenomenon. Nonetheless, IgM presence could not be correlated with any particular disease or the use of specific drugs. PMID- 8489345 TI - An implementation plan for autopsy quality control and quality assurance. AB - The few guidelines that exist for performing autopsy quality assurance are vague. Much has been written about the use of the autopsy to monitor clinical services, but not how to monitor the quality of the autopsy and autopsy reports. We present the comprehensive quality assurance program that has been developed and implemented at Hahnemann University Hospital, Philadelphia, Pa, for the past 2 years; this program has encompassed quality control of our diagnostic work. Key features have included in-depth peer review of completed reports, documentation of review at conferences, and careful monitoring of turnaround time. We have found that integrating quality assurance into departmental conferences is a useful supplement to in-depth peer review of randomly chosen autopsies. Our approach to quality assurance may serve as a model for other pathology departments, particularly those with pathology residency training programs. PMID- 8489346 TI - Periparotid lupus erythematosus panniculitis. Clinicopathologic correlation of two cases presenting as primary parotid disease. AB - Lupus erythematosus (LE) panniculitis, also called lupus profundus, is an uncommon but well-established manifestation of both chronic cutaneous (discoid) LE and systemic LE. Although LE panniculitis characteristically may involve the face, specific parotid and periparotid involvement has not, to the best of our knowledge, been previously reported. We describe the clinicopathologic correlation of two cases of LE panniculitis that presented as apparent primary parotid parenchymal disease; one as a neoplasm, the other as parotiditis. Failure to recognize LE panniculitis resulted in prolonged periods of inappropriate therapy and significant morbidity, including an unnecessary parotidectomy. Lupus erythematosus panniculitis has well-established histologic criteria that should be considered in the differential diagnosis of an unexplained parotid mass. PMID- 8489347 TI - Anergic disseminated toxoplasmosis in a patient with the acquired immunodeficiency syndrome. AB - Cerebral toxoplasmosis is the most common cause of focal brain disease in patients with the acquired immunodeficiency syndrome. A 24-year-old human immunodeficiency virus-infected woman with two previous episodes of Pneumocystis carinii pneumonia presented with diarrhea and fever. Despite antibiotic treatment, septic shock developed, and she died 3 weeks after the symptoms began. Histologic and histochemical studies revealed an anergic toxoplasmosis with dissemination in all examined organs. There were multiple foci of toxoplasmic cysts and free tachyzoites, sometimes with minute areas of necrosis, but no inflammatory reaction at all. Since effective treatment of toxoplasmosis is available, the occurrence of this rare form of toxoplasmosis should be kept in mind. PMID- 8489348 TI - Primary lymphoma of the kidney in the acquired immunodeficiency syndrome. AB - An increased incidence of lymphoma has been reported in patients with the acquired immunodeficiency syndrome. Malignant lymphomas that develop within this setting of impaired immune surveillance have distinctive clinical, histologic, and molecular biologic characteristics. Histologically, the majority of these lymphomas are small noncleaved cell or immunoblastic lymphomas, and are B-cell phenotype by immunophenotypic and immunoglobulin gene rearrangement studies. In contrast with malignant lymphoma occurring in the general population, extranodal origin is common in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas, with the central nervous system, bone marrow, gastrointestinal tract, and liver being the most common sites. To the best of our knowledge, there has been no description in the literature of primary renal lymphoma occurring in patients with the acquired immunodeficiency syndrome. We report an unusual case of primary non-Hodgkin's lymphoma (diffuse B-cell immunoblastic type) of the kidney in a patient with the acquired immunodeficiency syndrome. PMID- 8489349 TI - Mural bridging lesions in colonic Crohn's disease. AB - A case of Crohn's colitis with mural bridging lesions is described. The bridging lesions comprised colonic-type mucosa, smooth muscle, nerve fibers, with foci of adipose tissue and fibrous connective tissue. The lesions arose from the muscularis propria proximal to colonic strictures and possibly due to diverticular outpouching of the colonic wall associated with increased intraluminal pressure, although the exact mechanism of their formation appears unclear. This entity has not been previously described in inflammatory bowel disease, to our knowledge. Bridging pseudopolyps are seen in ulcerative colitis and rarely in Crohn's disease but do not contain substantial amounts of smooth muscle and/or nerve fibers. We believe that the mural bridges described in this article represent residual muscularis propria at the site of diverticular formation due to long-standing Crohn's colitis. We speculate that the stricture formation seen distal to the site of the mural bridging lesions may have been an important factor in formation of the colonic diverticula and, hence, these lesions that we interpret as representing residual muscularis propria adjacent to sites of diverticular formation in long-standing Crohn's colitis. PMID- 8489350 TI - An assessment of the contribution of electromyographic biofeedback as an adjunct therapy in the physical training of spinal cord injured persons. AB - This study tested the efficacy of biofeedback when administered in conjunction with physical rehabilitation therapy to chronic C5-7 quadriplegics. Triceps brachii, biceps brachii, wrist extensors, and wrist flexors were tested. The studied muscles were compromised by the injury to varying degrees, but were often still useful to these subjects. An exercise regimen was given to all subjects. In addition, subjects were separated into two groups: those who received biofeedback training and those who did not. Two measures of performance were tested: manual muscle scores and functional activities scores. Both groups scored significantly higher on both measures after 12 weeks of rehabilitation therapy. We found no evidence that biofeedback generally increased the amount of improvement seen. These results do not support the routine use of biofeedback in the treatment of chronic spinal cord injury, but rather further stress the importance of exercise therapy for such injuries. PMID- 8489351 TI - Determining residual urine volumes using a portable ultrasonographic device. AB - Residual urine volumes of 24 men with neurogenic bladder dysfunction were repetitively assessed 400 times with the BVI-2000 BladderScan portable ultrasonographic device prior to 100 episodes of intermittent catheterization. By comparing each examiner's first ultrasonographic measurement of urine volume with the catheterized urine volume, the mean error of the ultrasonographic measurements was -26mL (-11%) and the mean absolute error was 44mL (22%). The ultrasonographic measurements detected the presence of residual urine volumes of > or = 100mL with a sensitivity of 90% and a specificity of 81%. In the subset of catheterization episodes in which the catheterized urine volumes were < or = 200mL, the mean error of the ultrasonographic measurements was -15mL (-9%), the mean absolute error was 37 mL (28%), and the sensitivity and specificity were 77% and 81%, respectively. There was no clear advantage in using the average or maximum of two repeated ultrasonographic measurements over using each examiner's first ultrasonographic measurement alone. Increased examiner experience did not significantly decrease the errors encountered. PMID- 8489352 TI - Hydrocortisone and exercise effects on articular cartilage in rats. AB - The combined effects of hydrocortisone and running exercise on articular cartilage were assessed in female Sprague-Dawley rats. Animals were divided into three groups: 12 control (C), 12 who received an injection of 0.1 mL hydrocortisone once a week for three weeks (HC), and 12 rats who received three weekly injections of hydrocortisone and ran twice daily for six weeks (HC + run). Previous study revealed that rats that ran on a treadmill for three to 12 months did not have articular cartilage that was different from controls and thus a fourth group of rats, runners only, was not included in this analysis. At sacrifice, both knees were examined, photographed, and subsequently decalcified, then sectioned at 6 mu and stained. HC + run rats had significant more surface degeneration on femoral cartilage than HC or C rats. Eight of 12 HC + run rats displayed fibrotic invasion and/or subchondral bone replacement of degenerated articular cartilage, a feature not seen in HC or C rats. Cross-sections from HC + run rats displayed areas of cell death, and loss of matrix staining. Results suggest that, in rats, running exercise combined with intraarticular injections of hydrocortisone is more detrimental to articular cartilage than hydrocortisone or running alone. PMID- 8489353 TI - Training of ambulatory individuals with cerebral palsy. AB - The effect of training on the physical work capacity (PWC) and the physiological response to simulated tasks of seven ambulatory individuals with cerebral palsy (CP) were studied. Energy demand for each work task was determined by percentage of PWC (%PWC). Results indicate that an eight week training program increased the PWC as evaluated by an exercise test on the Schwinn Air-Dyne Ergometer. The performance of the individuals for the simulated tasks measured in %PWC increased significantly, suggesting that individuals with CP could benefit from a training program and would be able to work eight hours before experiencing fatigue. PMID- 8489354 TI - A follow-up study on the effects of training on the fitness and habitual activity patterns of 60- to 70-year-old women. AB - This study investigated the aerobic fitness, body composition, spirometric variables, Human Activity Profile, and level of adherence to physical activity subsequent to completion of a progressive walking program of six month's duration (T1). Sixty-six women previously randomized to training (TG) and control (CG) groups were reassessed six months after finishing the six month walking program (T2). During the follow-up period, 77.8% of the TG subjects continued with exercise and maintained lower (p < 0.005) exercise heart rates compared to the CG. A Mann-Whitney U test on the difference scores (T2-T1) revealed no difference (p > 0.05) between the TG and CG for changes in Maximum Current Activity and Normative Impairment Index, which are both components of the Human Activity Profile, with the earlier increases (p < 0.05) in these parameters by the TG having been maintained. Participation in a previous low frequency training regimen therefore resulted in elderly women adopting and sustaining a higher level of habitual physical activity. This is important because a favorable modification of lifestyle factors is likely to be indicative of an enhanced outlook for independence. PMID- 8489355 TI - Movement energetics of individuals with a history of poliomyelitis. AB - Principles for evaluating the functional capacity of, and, therefore, exercise testing, chronically-disabled populations such as individuals with a history of poliomyelitis are considerably less well established than those for able-bodied persons. Therefore, we examined the use of indexes of movement economy and cardiorespiratory conditioning based on the results of a submaximal exercise test and oxygen consumption studies in individuals with a history of poliomyelitis. Subjects (n = 48) were categorized into four distinct groups, ie, having normal movement economy and either normal (n = 12) or reduced cardiorespiratory conditioning (n = 11), or having reduced movement economy and either normal (n = 10) or reduced cardiorespiratory conditioning (n = 15). There was no relationship between the indexes of movement economy and cardiorespiratory conditioning (p > 0.05) supporting that these indexes reflected physiologically-distinct entities. Irrespective of movement economy, deconditioned subjects had a reduced forced vital capacity (% predicted) (p < 0.05) and a higher resting heart rate (HR) (p < 0.01) compared to conditioned subjects. The difference in resting HR was attributed to conditioning level rather than initial arousal because resting HR and VO2 were comparable on repeated tests (p > 0.05). Although there was no difference in steady-state HR (% predicted maximum) among the four groups (p > 0.05), VO2 (% pred max) was significantly lower for the deconditioned than the conditioned subjects (p < 0.01). We concluded that determining movement economy and cardiorespiratory conditioning with a submaximal exercise test may enhance assessment and treatment outcome evaluation, hence provide a rational basis for rehabilitation interventions in individuals with a history of poliomyelitis. PMID- 8489356 TI - The hemodynamic responses to upright exercise after orthotopic cardiac transplant. AB - The study was undertaken to examine the heart rate (HR) and stroke volume (SV) responses to upright exercise in patients after orthotopic cardiac transplantation (Group A). The findings were compared to data obtained from post coronary artery bypass surgery patients (Group B) and from healthy subjects (Group C). All three groups (n = 12 in each group) were matched for age and gender. The preexercise HR and blood pressure were significantly higher in Group A (p < 0.05), whereas the SV was significantly lower (41 +/- 4mL.beat-1 vs 63 +/- 3 and 65 +/- 2 mL.beat-1 in Group B and C respectively, p < 0.05). In Group A, at submaximal work loads, the SV was consistently lower than in Groups B and C. During the early phases of exercise, the HR was consistently higher in Group A also. Systemic vascular resistance remained significantly higher in Group A throughout exercise (p < 0.05). PMID- 8489357 TI - Health status and quality of life following cardiac transplantation. AB - There is little information regarding the functional status and quality of life of cardiac transplant patients. This investigation is the largest study describing outcome up to 10 years after cardiac transplantation. We conducted a cross-sectional survey of 200 cardiac transplant recipients using the Sickness Impact Profile and a supplementary questionnaire. The response rate was 48%. The median duration post-cardiac transplantation was 2.3 years (range, 0.5 to 9.7 years). The median age was 53 years (range, 27.1 to 68.7). In comparison to previously published studies, our sample of cardiac transplant recipients had worse quality of life than normals, similar scores to cardiac arrest survivors and post-myocardial infarction patients, and better quality of life than patients with low back pain. We found that those not working (44%) reported a lower quality of life. Musculoskeletal-neurologic complaints were highly prevalent, with generalized weakness in 54% responding, fatigue in 42%, and low back pain in 37%. Lower quality of life was found in patients reporting a higher number of musculoskeletal-neurological disorders. We conclude that there are specific areas for rehabilitation intervention in patients post-cardiac transplantation, and suggest areas for future research directed towards enhancing quality of life for cardiac transplant recipients. PMID- 8489358 TI - Physicians' practice patterns in pediatric electrodiagnosis. AB - The medical literature contains contradictory reports and recommendations regarding pediatric patients' pain and distress during electrodiagnosis. We surveyed 117 pediatric neurologists and physiatrists regarding their practice patterns in pediatric electrodiagnosis; 84 (72%) responded, of whom 44 (52%) regularly perform electrodiagnosis on children (mean = 85 per year, representing 3,667 examinations per year). Respondents reported extreme behavioral distress (eg, screaming, flailing, requiring additional restraint, or attempting to leave the examination table) in 35% of examinations, most often among 2- to 6-year olds. Pain medications are never prescribed by 45%, occasionally by 48%, and always by 2%; general anesthesia is never administered by 75%, occasionally by 21%. Only 32% reported that any psychological intervention is routinely offered to enhance child coping. Wide variability was found in physicians' preferences about parental presence, order of examinations, demonstration of procedures, and other aspects of electrodiagnosis. PMID- 8489359 TI - Medial paraspinal muscle electromyography: techniques of examination. AB - We describe two techniques, developed through cadaveric dissections, for the electromyographic examination of the lumbar interspinal muscles and medial lumbar multifidi. Previous anatomic studies have indicated that these medial paraspinal muscles share unisegmental innervation by a single nerve root. Electromyography of these muscles may therefore improve the localization of lumbosacral radiculopathy. The ability of the two techniques to achieve appropriate needle placement was confirmed using percutaneous injection of colored latex into cadavers. The safety and feasibility of the techniques were confirmed in healthy volunteers. Further studies are underway in subjects with lumbosacral radiculopathy to determine the clinical utility of these techniques. PMID- 8489360 TI - Effect of ankle joint position on electrically evoked surface myoelectric signals of the tibialis anterior muscle. AB - The relationship between surface myoelectric signal variables and ankle joint angle is studied in the tibialis anterior muscle of ten normal subjects during electrical stimulation of the main muscle motor point in isometric conditions. Rectangular current pulses of 0.1 ms width and 20Hz repetition rate were applied for 10s with a monopolar technique using a stimulation/detection system providing stimulation artifact suppression. Electrically evoked responses (M-waves) were detected with a four-bar electrode placed on the skin below the lowest motor point near the tendon end of the muscle. Average rectified value, root mean square value, mean and median spectral frequency, conduction velocity, and latency of the surface signal were computed for ankle angles of 15 degrees dorsal flexion (-15 degrees), 0 degrees, 15 degrees, 30 degrees and 45 degrees of plantar flexion. All variables were considerably affected by the joint angle. Spectral variables and latency showed a statistically significant decrement as angle increased from -15 degrees to 45 degrees whereas conduction velocity and amplitude variables had a less regular behavior. The evoked response showed a latency decrement and a change of shape (mostly a widening of the second phase), as ankle joint angle increased from -15 degrees to 45 degrees. In most subjects conduction velocity appeared to be over estimated at -15 degrees and 45 degrees, a fact attributed to the small distance between the electrodes and either the tendon or the innervation zone at these two angles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489361 TI - Muscle damage progression in Duchenne muscular dystrophy evaluated by a new quantitative computed tomography method. AB - The progression of muscle damage was studied in the lower extremity and trunk muscles of patients with Duchenne muscular dystrophy (DMD) with a new quantitative computed tomography (CT) method. The degree of muscle fiber loss and fat tissue replacement was quantified using the indices of percent cross sectional area (%CSA) of muscle and fat, or the percentages of the area having the CT numbers of normal muscle and fat. A cross-sectional study in 71 patients showed that as the disability stage progressed, both CT number and %CSA of muscle decreased while %CSA of fat increased. The rate of progression was different for each muscle, and the order of involvement was clarified. The CT findings were also significantly correlated with muscle strength, indicating validity of our method. Our findings of the natural course of muscle involvement would be useful in providing appropriate rehabilitative care as well as assessing the efficacy of therapeutic interventions. PMID- 8489362 TI - Anaerobic threshold and maximal oxygen consumption during arm cranking exercise in paraplegia. AB - The major purpose of this investigation was to compare the anaerobic threshold (AT) and maximal cardiopulmonary responses to arm exercise between persons with paraplegia and the able-bodied. The locomotive stress on the heart in paraplegic subjects was also examined. Thirty-nine paraplegic subjects (T1-L4 lesions) and 32 able-bodied subjects completed a continuous, progressive, resisted arm cranking exercise test. The AT was determined from the ventilatory parameters. At the AT, the mean values of Vo2/body weight (BW) for class II (T1-T5, N = 9), III (T6-T10, N = 11), and IV (T11-L4, n = 19) paraplegic subjects were 10.9, 13.2, and 13.5mL/kg/min, respectively, and only class II had significantly lower value than the able-bodied (14.4mL/kg/min). During maximal exercise, the mean values of maximal oxygen consumption per body weight (Vo2max/BW) for class II and III paraplegics were 17.4 and 17.7mL/kg/min, respectively, which were significantly lower (p < 0.05) than that of class IV (21.3mL/kg/min) and the able-bodied (28.2mL/kg/min). The heart rate (HR) during wheelchair-propelling (119bpm, n = 37) was significantly less than that at the AT (134bpm), but the HR during crutch walking (151bpm, n = 17) was significantly higher. The results indicate that both submaximal and maximal cardiopulmonary functions in high-lesion paraplegics were less than that of the able bodied. Furthermore, the intensity of wheelchair propelling at comfortable speed is not enough for improving the cardiopulmonary functions. PMID- 8489363 TI - The relationship between comfortable and most metabolically efficient walking speed in persons with unilateral above-knee amputation. AB - Walking is most efficient when the least energy is spent over a certain distance. In six normal male subjects and 11 males with above-knee amputation the comfortable self-selected walking speeds and the most metabolically efficient walking speeds were determined. For that purpose energy expenditure was measured per second and per meter at six incremental walking speeds. Heart and step rate were registrated also at each walking speed. The results showed that in subjects who have not undergone amputation the comfortable walking speed is the same as the most efficient walking speed. However, in the above-knee amputee group, the comfortable walking speed is lower than the most efficient walking speed. When both groups walked at their own efficient walking speed they had the same energy expenditure per second. PMID- 8489364 TI - Electronic pressure algometry of deep pain in healthy volunteers. AB - Deep pressure pain threshold (PPT) and pressure pain tolerance (PPtol) were measured by pressure algometry at the mastoid processes, external malleoli, and sternum in 24 healthy volunteers. The algometer consisted of a force displacement transducer with a 0.25 cm2 pressure tip linked to a recorder. The rate of force application was approximately 1kg/sec/0.25cm2. High intersubject variation was noted at all sites for both PPT and PPtol. Mean PPT and PPtol values at the sternum were 5.2kg +/- 2.1 and 8.1kg +/- 2.4, respectively, and significantly higher than at the other sites. PTT did not differ significantly between the sexes or between dominant and nondominant sides. PPtol, on the other hand, was lower in the women, but significantly so only at the malleoli. On repeat examination, comparison between the mean values at each site showed no statistical differences in any instance. Pressure algometry, as used in this study in healthy subjects, proved a reliable technique for the estimation of deep PPT and PPtol values. It may possibly serve for screening the response to experimental pain in various groups of pain patients. PMID- 8489365 TI - A validation of the functional independence measurement and its performance among rehabilitation inpatients. AB - The Functional Independence Measurement (FIM) is a new functional status instrument for use among rehabilitation inpatients, but its validity and reliability have been only partially established. Because of its rapid dissemination, we sought further evidence concerning the FIM's internal consistency, responsiveness over time, and construct validity. We examined Uniform Data System (UDS) data on 11,102 general rehabilitation inpatients from the Pacific Northwest. Mean age was 65 and 51% were male. The most common diagnoses were stroke (52%), orthopedic conditions (10%), and brain injury (10%). Internal consistency of the FIM was calculated using Cronbach's alpha. To assess FIM responsiveness, we examined differences between admission and discharge FIM scores. For construct validation purposes, we hypothesized that the FIM would vary with age, comorbidity, discharge destination, and impairment severity. Comorbidity was quantified with the Charlson Comorbidity Index. The FIM had a high overall internal consistency (discharge FIM alpha = .93). The FIM registered significant functional gains during rehabilitation (33% FIM score improvement, p < .001), as do many other functional status indicators. The greatest and least functional improvements were observed for traumatic brain injury and low back pain (53% and 8% FIM score improvement, respectively). The FIM discriminates patients on the basis of age, comorbidity, and discharge destination. Severity differences could be distinguished among spinal cord injury and stroke patients. We conclude that the FIM has high internal consistency and adequate discriminative capabilities for rehabilitation patients. It is a good indicator of burden of care, and demonstrates some responsiveness, but its capacity to measure change over time needs further examination and comparison with competing scales. PMID- 8489366 TI - Progressive supranuclear palsy: clinical presentation and rehabilitation of two patients. AB - Progressive supranuclear palsy (PSP), is an infrequent movement disorder characterized by supranuclear ophthalmoplegia, pseudobulbar palsy, and axial dystonia with frequent and unpredictable falls, usually backward. Median survival from time of diagnosis is two years. When diagnosis is reached, the patients are usually disabled and unable to ambulate independently. No specific rehabilitation protocol has been described for PSP. This article examines our rehabilitation experience with two PSP patients and our management of their frequent and unpredictable falls. The rehabilitation program consisted of a thorough physical evaluation; cognitive and speech evaluation and training; exercises to improve strength and coordination; and static and dynamic balance training. In order to improve safety during ambulation, we provided the patients with a heavy shopping cart or wheelchair that they could grab when in danger of losing their balance. The patients were able to achieve independence in ambulation. PMID- 8489367 TI - Forearm pain secondary to compression of the medial antebrachial cutaneous nerve at the elbow. AB - We report the case of a 42-year-old man whose only symptom was pain in the medial aspect of the left forearm. There were no paresthesiae and the clinical examination was normal except for the presence of a small lipoma at the elbow. Electromyographic examination confirmed the normality of the main nerve trunks of the left upper limb and demonstrated abnormalities of the left medial antebrachial cutaneous nerve when compared with the right side. On the basis of this finding, a local corticosteroid injection was performed, which rapidly and lastingly relieved the pain (no recurrence after 18 months). PMID- 8489368 TI - Thalamic infarction secondary to cervical manipulation. AB - Vertebrobasilar infarction is a well documented complication of cervical manipulation. A commonly proposed pathogenesis is an intimal tear of the vertebral artery leading to cerebellar and other posterior fossa lesions. However, there have been no cases of thalamic infarct reported. This case demonstrates a thalamic infarction concurrent with brainstem and cerebellar infarction secondary to cervical manipulation and intimal tearing of the vertebral artery. Immediately following manipulation, the patient developed nystagmus, quadriparesis, and a speech deficit. After an aggressive course of in patient rehabilitation, the patient progressed to a community ambulator with deficits in speech and perception. This case demonstrates one of the inherent risks associated with repetitive forceful cervical manipulation. PMID- 8489369 TI - Coexistence of deep venous thrombosis and heterotopic ossification in the pediatric patient. AB - A 14-year-old girl and a 15-year-old boy with severe traumatic brain injuries were noted to have marked asymmetry in the lower extremities. Clinical and radiologic evaluation demonstrated the coexistence of deep venous thrombosis (DVT) and heterotopic ossification (HO). These cases demonstrate that although DVT are rare in children, they can be present and may coexist with the more common presentation of a swollen lower extremity secondary to HO. PMID- 8489370 TI - Posttraumatic osseous tunnel formation causing sciatic nerve entrapment. AB - Sciatic nerve entrapment in an osseous tunnel has only been reported twice previously. We describe a 19-year-old man evaluated for left lower limb pain and weakness that began one and one half years after sustaining stab wounds to the left buttock and midline back near the T11 vertebrae. The patient had sciatica and demonstrated motor and sensory deficits on physical exam. Electrodiagnostic studies demonstrated a localized injury to the sciatic nerve in the proximal thigh. Radiographic studies of the left pelvis and femur showed an 8 to 10cm linear opacification overshadowing the left femoral head and anatomic neck. An arteriogram of the left leg demonstrated a 3 x 4cm lobulated aneurysm arising from the distal portion of the inferior gluteal artery. Surgical exploration revealed the sciatic nerve to be encased in cylindrical bone. The ectopic bone was removed and the sciatic nerve released. The patient had gradual improvement with a nearly complete neurological recovery by three months after surgery. PMID- 8489371 TI - Geriatric rehabilitation. 1. Social, attitudinal, and economic factors. AB - This self-directed learning module highlights the social, attitudinal, and economic factors that are important in the rehabilitation of the older adult. It is part of the chapter on geriatric rehabilitation in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article contains information on the epidemiology of aging and disability, geriatric rehabilitation treatment environments, social support systems, reimbursement issues, and ageism. PMID- 8489372 TI - Geriatric rehabilitation. 2. Diagnosis and management of acquired disabling disorders. AB - This self-directed learning module highlights the diagnosis and rehabilitation management of acquired disabling disorders. It is part of the chapter on geriatric rehabilitation in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article contains information on the physiology of aging; rehabilitation management of pathologic conditions of the older adult affecting the cardiovascular, pulmonary, skeletal, connective tissue, and neurologic systems; rehabilitation issues relating to psychologic functioning of the older adult; pharmacologic concerns of the older adult; and response to illness with aging. PMID- 8489373 TI - Geriatric rehabilitation. 3. Mid- and late-life effects of early-life disabilities. AB - This self-directed learning module highlights mid- and late-life effects of early life disabilities. It is part of the chapter on geriatric rehabilitation in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article contains information on how to evaluate, prevent, and manage late complications seen in adults and older adults with cerebral palsy, spina bifida, spinal cord injury, multiple sclerosis, juvenile rheumatoid arthritis, and early-life amputations, including psychosocial and other quality-of-life issues. New advances in post-polio syndrome are also covered. PMID- 8489374 TI - Geriatric rehabilitation. 4. Assessment, preservation, and enhancement of fitness and function. AB - This self-directed learning module highlights the assessment, preservation, and enhancement of fitness and function in the older adult. It is part of the chapter on geriatric rehabilitation in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article contains information on functional assessment, deconditioning, exercise testing and physiology, gait disorders and falls, sports injuries, and industrial injuries in the older adult. PMID- 8489375 TI - Sports medicine. 1. The physiatric approach. AB - This self-directed learning module highlights key elements in this topic area. It is part of the chapter on sports medicine in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article covers the role of the physiatrist in sports medicine and presents an overview of the diagnosis, treatment, and prevention of sports-related injuries. We describe how the physiatrist relates to other sports medicine practitioners and detail the stepwise physical examination of an injured athlete by a physiatrist. PMID- 8489376 TI - Sports medicine. 2. Upper extremity injuries. AB - This self-directed learning module highlights recent advances in this topic area. It is part of the chapter on sports medicine in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. In this article, shoulder and elbow problems of the throwing athlete are emphasized. Common injuries involving the wrist and hand are also covered. PMID- 8489377 TI - Sports medicine. 3. Lower extremity injuries. AB - This self-directed learning module highlights new advances in sports-related injuries of the lower extremity. It is part of the chapter on sports medicine in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article contains sections on injuries of the hip and thigh, knee and leg, and ankle and foot. The most common injuries are primarily addressed, while less common injuries are more briefly discussed. New advances that are covered in this section include closed kinetic chain strengthening exercises and recent advances in rehabilitation after anterior cruciate ligament reconstruction. PMID- 8489378 TI - Sports medicine. 4. Spine and head injuries. AB - This self-directed learning module highlights important aspects of athletic spine and head injuries. It is part of the chapter on sports medicine in the Self Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article covers the presentation, pathomechanics, and classification of common and important cervical and lumbar injuries. Sports participation criteria for children with spine deformities are discussed. In addition, a description of the degrees of concussion, the general guidelines for return to play after a sports-related head injury, and postconcussion sequelae are reviewed. PMID- 8489379 TI - Sports medicine. 5. The physiatrist as team physician. AB - This self-directed learning module highlights important aspects of the evaluation and care of the injured athlete by a team physician. It is part of the chapter on sports medicine in the Self-Directed Medical Knowledge Program for practitioners and trainees in physical medicine and rehabilitation. This article covers the components of a preparticipation examination, the on-field evaluation of head, spine, and limb injuries, and return-to-play criteria after specific injuries. Sports medicine for the physically challenged athlete, medicolegal considerations for the team physician, and anabolic steroids are also reviewed. PMID- 8489380 TI - Some thoughts of a trauma surgeon. PMID- 8489381 TI - Laparoscopic cholecystectomy. A statewide experience. The Connecticut Laparoscopic Cholecystectomy Registry. AB - The explosion in laparoscopic cholecystectomy has posed many questions about its safety compared with the "gold standard" of open cholecystectomy. A statewide database was established in Connecticut to study these issues. Thirty-three (97%) of 34 hospitals in Connecticut participated in the study, which began at the inception of the laparoscopic procedure. Four thousand six hundred forty laparoscopic cholecystectomies were performed between May 1, 1990, and September 30, 1991. The overall conversion rate to open cholecystectomy was 6.9%. Conversions were more frequent with acute cholecystitis, in the elderly, and early in a surgeon's experience. The overall technical complication rate was 4.7%; common bile duct injuries occurred in 15 patients (0.3%). Complications decreased with increasing experience, to 0.98% after a surgeon's 75th procedure. Six patients (0.13%) died following laparoscopic cholecystectomy. The overall mortality rate associated with cholecystectomy fell during the study period. The frequency of cholecystectomy in Connecticut increased 29% with the advent of the laparoscopic procedure. The introduction of laparoscopic cholecystectomy has resulted in an increased frequency of surgery without an increase in surgical mortality. The incidence of common bile duct injuries was low. The decreasing incidence of technical complications demonstrates the learning curve for the procedure. PMID- 8489382 TI - Long-term results of the ileoanal pouch procedure. AB - Many surgeons consider the ileoanal pouch procedure to be the procedure of choice for patients who require surgery for ulcerative colitis and familial adenomatous polyposis. To determine long-term results, 460 patients (mean +/- SD age, 31 +/- 9 years) who underwent the ileoanal pouch procedure from 1980 through 1991 were prospectively observed by computerized registry. The leading indication for operation was ulcerative colitis (n = 382; 83%). A J-shaped reservoir was created in 434 patients (94%). More than 5 years after ileostomy closure, the mean number of bowel movements was 5.8 +/- 2.2, and 13% of patients had leakage. Most patients (94%) were satisfied with their results. Sixteen patients (3.5%) required recreation of a permanent stoma for pouch failure. Complications (major and minor) occurred in 266 patients (58%) and included obstruction (n = 94; 20%), pouch fistula (n = 26; 6%), anastomotic stricture (n = 40; 9%), anastomosis separation (n = 14; 3%), and pouchitis (n = 83; 18%). Modifications in technique and increased operative experience have significantly decreased the incidence of obstruction (P = .05) and pouch-related complications (P = .004). Despite complications, long-term results are acceptable, and patient satisfaction remains high. PMID- 8489383 TI - Continuing trends in the prevalence of right-sided lesions among colorectal carcinomas. AB - The shift of colorectal carcinoma location toward the proximal colon has been reported. This study documents that this statistically significant trend has continued through 1992. An increase in transverse and descending colon cancers is now apparent also. Only 59% of all large-bowel cancers occurred distal to the descending colon between 1978 and 1992. Both right-sided and distal large-bowel cancers have significantly decreased in size, yet the incidence and frequency of lymph node metastases have not changed over a 65-year interval (from 1928 to 1992). This constant proportion of lymph node metastases may suggest distinct biological subsets of cancers (lymph node avid vs lymph node avoidance). The progression from small size with fewer metastases to large size with more lymph node metastases occurs only in some of the smallest distal colorectal cancers. PMID- 8489384 TI - Breast cancer and earlier detection efforts. Realized and unrealized impact on stage. AB - OBJECTIVE: To test our hypotheses that increased public and professional education in breast cancer detection (screening mammography, clinical breast examination, and breast self-examination) would lead to detection at earlier stages of disease with each of the three methods. DESIGN AND SETTING: A survey study of all pathologically diagnosed breast cancers in a defined geographic area (all nonfederal general hospitals in the state of Vermont) before (1975-1984, n = 1652) and after (1989-1990, n = 683) screening mammography became more commonly used. MAIN OUTCOME MEASURES: Method of detection of breast cancer and stage at detection. RESULTS: The age-adjusted annual incidence rate of breast cancer among adult women was 99 per 100,000 during the years 1975 to 1984 compared with 169 per 100,000 during 1989-1990 (P < .001). Mammography as the method of detection increased in use from 2% to 36% (P < .001). In the later era, invasive breast cancers were detected at more favorable TNM stage (P < .001); mean maximum tumor diameter was smaller (2.2 cm vs 2.7 cm; P < .001); percentage of histologically positive nodes was lower (37% vs 47%; P < .001). When mammographically detected cancers were excluded from the analysis of invasive cancers, the mean maximum tumor diameter and percentage of negative nodes in the two eras were similar even though there was an apparent shift to detection at an earlier clinical stage. CONCLUSION: The earlier stages of detection and the sudden increase in incidence could almost entirely be credited to screening mammography. Mammographic screening had a much greater impact on stage at detection in women aged 50 years and older than in those younger than 50 years. PMID- 8489385 TI - Laparoscopic appendectomy. A safety and cost analysis. AB - To assess the feasibility of laparoscopic appendectomy, we reviewed hospital records and charge data for all patients older than age 15 years who underwent appendectomy between November 1990 and July 1992. Fifty-eight patients underwent laparoscopic appendectomy and 206 patients underwent conventional appendectomy. Intraoperative (1.9%) and postoperative (5.8%) complication rates were low. The rate of conversion to conventional appendectomy was 7.7%. Hospital stay and charge analysis was performed on a cohort of 52 patients undergoing laparoscopic appendectomy and 180 patients undergoing conventional appendectomy. Total costs were similar. The most notable difference between the two groups was the operating room supply charge; this negated any cost savings achieved by the reduced length of stay following laparoscopic appendectomy. Laparoscopic appendectomy is a safe alternative to conventional appendectomy; it shortens hospital stay and allows patients to resume normal activity more quickly than conventional appendectomy. PMID- 8489386 TI - Determination of tumor aggressiveness in colorectal cancer by K-ras-2 analysis. AB - Markers that predict tumor aggressiveness on a case-by-case basis would enable individualization and optimization of oncologic therapy. To achieve this goal, the presence and specific type of K-ras-2 point mutation was determined from formalin-fixed, paraffin-embedded tissue sites in 247 primary and 166 metastatic recurrent colorectal adenocarcinomas, using a novel approach consisting of topographic tissue selection, DNA amplification, and direct sequencing applicable to large and needle-biopsy-sized specimens. The results provide the basis for a genotypic classification of colorectal cancer capable of predicting individual tumor aggressiveness, including the pattern and extent of metastasis. PMID- 8489387 TI - Surgical repair of esophageal perforation due to pneumatic dilatation for achalasia. Is myotomy really necessary? AB - Esophageal perforation is a rare complication of pneumatic dilatation for achalasia. The few clinical series reported in the literature recommend, under most circumstances, esophageal repair combined with esophagocardiomyotomy. However, the superiority of this technique over repair alone has never been proven. We reviewed our experience, since 1979, with six operative cases of esophageal perforation from pneumatic dilatation for achalasia. After debridement, the esophagus was repaired and, if possible, buttressed with a gastric fundal patch. There was only one late postoperative death due to sepsis and one upper gastrointestinal bleeding complication in our series. Follow-up (1 to 12 years) revealed no dysphagia in any of the five surviving patients and mild gastroesophageal reflux in two. From a review of the literature we found no reports of similarly treated patients experiencing recurrent symptoms of achalasia. In these acutely ill patients, our operative strategy is more feasible than repair and esophagocardiomyotomy and equally effective. PMID- 8489388 TI - Sphincter-saving alternatives in the management of adenocarcinoma involving the distal rectum. 5-year follow-up results in 40 patients. AB - We reviewed the treatment outcome in 40 patients undergoing full-thickness local excision (seven patients) or electrocoagulation (33 patients) for adenocarcinoma of the rectum. Patients were followed up for a minimum of 5 years or until death (mean follow-up, 7.6 years). Twenty-two patients (55%) survived 5 years free of disease or were free of disease at the time of death due to other causes following local treatment. Eight (62%) of 13 patients with persistent or locally recurrent disease were successfully treated with additional local therapy, rectal resection, or combined radiation therapy and chemotherapy. Overall, 30 (75%) of 40 patients embarking on a program of local treatment for carcinoma of the rectum survived 5 years free of disease or were free of disease at the time of death due to other causes. PMID- 8489389 TI - Routine cholangiography is not warranted during laparoscopic cholecystectomy. AB - The role of intraoperative cholangiography during laparoscopic cholecystectomy was prospectively evaluated in 514 patients undergoing laparoscopic cholecystectomy. Before surgery, all patients were assigned to one of three groups depending on the likelihood of their having common bile duct stones. Stratification was based on objective historical, laboratory, or radiologic criteria. In 453 patients deemed unlikely to have stones, laparoscopic cholecystectomy was performed without cholangiography. Of these patients, four had retained stones (0.9%). In 25 patients likely to have stones, preoperative endoscopic retrograde cholangiopancreatography identified stones in six patients (24%). In 36 patients whose likelihood of having stones was deemed indeterminate, intraoperative cholangiography was performed at laparoscopic cholecystectomy. A common bile duct stone was identified in one patient (2.8%). One common bile duct injury occurred in the group deemed unlikely to have stones, and this injury would not have been prevented by intraoperative cholangiography. We conclude that preoperative assessment will identify common bile duct stones and that routine cholangiography is not warranted. Meticulous dissection of the cystic duct at its origin at the infundibulum will prevent common bile duct injury. PMID- 8489390 TI - Portal vein thrombosis after elective splenectomy. An underappreciated, potentially lethal syndrome. AB - We describe seven cases of thrombosis of the portal and splenic vein after elective splenectomy. The diagnosis was initially unrecognized in all patients and was confused with biliary sepsis (three cases), postoperative pancreatitis (three cases), or pulmonary emboli (one case). Two patients in whom the diagnosis of portal vein thrombosis was not made within 3 days of disease onset died. In the five survivors, the diagnosis was based on clinical suspicion, confirmed with color flow Doppler ultrasonography or computed tomography with intravenous contrast material, and treated with thrombolytic agents, anticoagulants, and antibiotics. In two patients, splenic vein thrombus was visualized on initial postoperative imaging studies and the thrombus subsequently extended into the portal vein. Portal vein thrombosis should be considered in patients with fever and abdominal complaints after splenectomy. Urgent treatment with thrombolysis and anticoagulants may preserve bowel integrity and be lifesaving. PMID- 8489391 TI - The epidemiology of traumatic death. A population-based analysis. AB - Despite the proliferation of trauma systems, there are no population-based data describing the epidemiology of traumatic death. To provide these data, we reviewed all trauma deaths occurring in San Diego (California) County during 1 year. There were 625 traumatic deaths during the study (27.3 deaths per 100,000 population per year). Motor vehicle trauma was the most common cause of injury leading to death (N = 344 [55.2%]; 15.0 annual deaths per 100,000 population). Central nervous system injuries were the most common cause of death (48.5%, or 13.2 deaths per 100,000 population per year). Sepsis was responsible for only 2.5% of the overall mortality. Based on life-table data, traumatic death resulted in an annual loss of 1091 years of life per 100,000 and an annual loss of 492 years of productivity per 100,000. Injury continues to account for an enormous loss of life despite improvements in survival wrought by trauma systems. PMID- 8489392 TI - Improved quality of diabetic foot care, 1984 vs 1990. Reduced length of stay and costs, insufficient reimbursement. AB - Ischemic foot ulceration in the diabetic patient is a source of great physical and emotional strain for the patient and represents a significant financial burden for the health care system responsible for the cost of such care. Limb salvage remains the primary therapeutic goal; yet, fiscal constraints imposed by diagnosis related group-based reimbursement systems require maximal cost efficiency in the care process. Between 1984 and 1990, the changes in our team management approach to this problem, emphasizing aggressive surgical revascularization of threatened limbs, have improved the quality of care and dramatically reduced the major and minor amputation rate. In the process, we have reduced the length of hospital stay and the overall cost of care. Despite this improvement in outcome and efficiency, Medicare reimbursement remains insufficient, with an average loss of $7480 per admission. PMID- 8489393 TI - Evaluation of right ventricular function during aortic operations. AB - The simultaneous measurements of mixed venous oxygen saturation (SvO2) and right ventricular ejection fraction (RVEF) have now made it possible to precisely define and correlate the various hemodynamic changes that occur during abdominal aortic operations. Twenty-five patients undergoing infrarenal abdominal aortic aneurysm repair were examined with a pulmonary artery catheter capable of continuously measuring SvO2 and RVEF. With aortic clamping, significant reductions in cardiac index, stroke volume index, and right ventricular end diastolic volume index (RVEDVI) were noted, while RVEF remained unchanged. Following unclamping of the aorta, a significant reduction in SvO2 occurred, accompanied by an increase in mean pulmonary artery pressure and in pulmonary vascular resistance. Despite the increase in afterload, RVEDVI and RVEF did not change after unclamping. These preliminary data suggest that right ventricular function is preserved during abdominal aortic aneurysm repair. PMID- 8489394 TI - A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. AB - Acute pancreatitis is a protean disease capable of wide clinical variation, ranging from mild discomfort to apocalyptic prostration. Moreover, the inflammatory process may remain localized in the pancreas, spread to regional tissues, or even involve remote organ systems. This variability in presentation and clinical course has plagued the study and management of acute pancreatitis since its original clinical description. In the absence of accepted definitions for acute pancreatitis and its complications, it has not been possible to devise a clinical classification system useful for case management. Following 3 days of group meetings and open discussions, unanimous consensus on a series of definitions and a clinically based classification system for acute pancreatitis was achieved by a diverse group of 40 international authorities from six medical disciplines and 15 countries. The proposed classification system will be of value to practicing clinicians in the care of individual patients and to academicians seeking to compare interinstitutional data. PMID- 8489395 TI - Incidence, characteristics, and outcome of spinal cord injury at trauma centers in North America. AB - Acute spinal cord injury occurred in 2.6% of the 114,510 patients entered into the Major Trauma Outcome Study from 1982 to 1989. The most common causes of spinal cord injury were motor vehicle accidents (40%), falls (20%), and gunshot wounds (13.6%). Almost 80% of patients with spinal cord injury had multiple injuries. Cervical cord injury was seen in 65% of patients with isolated spinal cord injury, but in only 52% of patients with multiple injuries. The hospital mortality rate was 17%, with patients with multiple injuries having a significantly higher mortality rate than patients with isolated spinal cord injury (19.8% vs 6.9%). The TRISS method overpredicted the mortality rate among patients with multiple injuries (450 vs 379), but not among those with isolated injury. A program for better national surveillance and prevention of spinal cord injury is warranted. PMID- 8489396 TI - Autoamputation of appendix and the 'absent' appendix. PMID- 8489397 TI - Cost-effective hernia repair. PMID- 8489398 TI - On the late effects of surgery. PMID- 8489399 TI - Hypothesis: calcitriol mediates pregnancy's protective effect on multiple sclerosis. PMID- 8489400 TI - The planum temporale. PMID- 8489401 TI - Anomalous cerebral structure in dyslexia revealed with magnetic resonance imaging. AB - OBJECTIVE: To develop quantitative methods for identifying cerebral anomalies on magnetic resonance images of subjects with language disorders and other learning disabilities. DESIGN: Partially blinded comparison of subjects with dyslexia, unaffected relatives, and a control group balanced for age and socioeconomic status. Criterion standard: clinical diagnosis of dyslexia by physician or learning disabilities specialist on the basis of clinical assessment and family history. SETTINGS: Hospital pediatric neurology clinic and private reading clinic. PATIENTS AND OTHER PARTICIPANTS: VOLUNTEERS: individuals with dyslexia (seven male and two female, aged 15 to 65 years) from professional families; unaffected first- and second-degree relatives (four male and six female, aged 6 to 63 years) available in the geographical area; and controls (five male and seven female, aged 14 to 52 years). INTERVENTIONS: Gradient echo three dimensional scan in Seimens 1-Tesla Magnetom; 128 1.25-mm consecutive sagittal images. MAIN OUTCOME MEASURES: (1) Average length of the temporal (T) and parietal (P) banks of the planum temporale; (2) interhemispheric coefficients of asymmetry for T and P banks: Left-Right interhemispheric coefficients of asymmetry = (L-R)/[(L+R)/2]; (3) intrahemispheric coefficients of asymmetry = (T P)/[(T+P)/2]; and (4) qualitative assessment of gyral variants in the parietotemporal operculum. RESULTS: All groups had left-sided asymmetry for the temporal bank and right-sided asymmetry for the parietal bank. The group with dyslexia had exaggerated asymmetries, owing to a significant shift of right planar tissue from the temporal to parietal bank. They also had a higher incidence of cerebral anomalies bilaterally (subjects with dyslexia, six of nine; relatives, two of 10; and controls, zero of 12). CONCLUSIONS: Quantitative assessment of high-resolution magnetic resonance images can reveal functionally relevant variations and anomalies in cerebral structure. Further refinement of these measurement techniques should improve the diagnosis, classification, and treatment of language disorders and other learning disabilities. PMID- 8489402 TI - Atypical Leber's hereditary optic neuropathy with molecular confirmation. AB - OBJECTIVE: Leber's hereditary optic neuropathy (LHON) is typically a familial disease of primarily young, male adults. Analysis of mitochondrial DNA has identified point mutations associated with LHON and allowed us to identify cases of LHON not consistent with traditional descriptions of the disease. DATA SOURCES: The collective experience of three tertiary referral centers contributed to this report. STUDY SELECTION: Patients with bilateral optic neuropathies who were positive for the 11778 LHON mutation were included in this study if they were female and there was no family history of visual loss. DATA EXTRACTION: Six case histories are presented. DATA SYNTHESIS: The diagnosis of LHON remained unknown in six female patients with bilateral optic neuropathies until molecular analysis revealed the 11778 mitochondrial DNA mutation. None of the patients had a family history of visual loss, and five were initially diagnosed as having factitious visual loss. Other individual features atypical for LHON included lack of the characteristic LHON funduscopic appearance, bitemporal hemianopia, optic disc cupping, and premonitory episodes of transient visual loss. In one patient the correct diagnosis was delayed 17 years. CONCLUSIONS: The diagnosis of LHON should be considered in all cases of unexplained optic neuropathy, including those with negative family history, late or early age at onset, female gender, or normal funduscopic appearance. PMID- 8489403 TI - Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride. AB - Human postmortem and animal experimental results suggest a decline of the cerebral dopaminergic neuronal system with age. In this study, the radiotracer carbon 11-labeled-raclopride and positron emission tomography were applied to determine the effect of age on striatal D2 dopamine receptors in 32 healthy volunteer subjects (age range, 21 to 68 years; median, 31 years). An index of specific 11C-raclopride binding was calculated for putamen, caudate nucleus, and other brain regions in each subject. A significant decrease with age of the index for specific tracer uptake was found in putamen and caudate nucleus. The decrease was steep until 30 years, but slower afterward. After approximately 30 years of age, the decline of specific 11C-raclopride binding in putamen was found to be 0.6% per year. Our results suggest that D2 dopamine receptor binding sites (mainly postsynaptically located) decrease as a consequence of normal aging in parallel with the decline of the presynaptic nigrostriatal dopaminergic neuronal system. PMID- 8489404 TI - Spinal fluid cells and protein in amyotrophic lateral sclerosis. AB - The cerebrospinal fluid total protein in 385 cases of sporadic amyotrophic lateral sclerosis showed no relationship to survival, but it was related to survival time in 34 cases of familial amyotrophic lateral sclerosis. Infrequent and mild pleocytosis, and oligoclonal bands seemed to have no clinical significance in well established cases of amyotrophic lateral sclerosis. PMID- 8489405 TI - Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging. AB - The pathologic correlates of increased signal in the white matter of the centrum ovale in postmortem magnetic resonance imaging were investigated in an unselected series of 15 autopsies. Two types of magnetic resonance imaging hyperintensities could be separated on the basis of size (10-mm cutoff): extensive and punctate. The pathologic basis of extensive hyperintensities was large areas of pallor with ill-defined margins, located in the central white matter and sparing the subcortical U fibers on both myelin and axonal stains. Microscopically, these areas showed diffuse vacuolation and significant reduction in the areal densities of glial cells. This change was never seen in areas that did not show extensive white matter hyperdensities on magnetic resonance imaging. The correlates of punctate magnetic resonance imaging hyperintensities were less well defined; dilated Virchow-Robin spaces probably represent a common cause of this phenomenon. PMID- 8489406 TI - Thalamic stimulation and proximal tremor. A specific target in the nucleus ventrointermedius thalami. AB - The severe proximal cerebellar postural tremor (also called action or intention or hyperkinetic tremor) is barely influenced by thalamotomy or stimulation of the thalamus at the classic target in the lower part of the nucleus ventrointermedius thalami (VIM). In four patients with a severe postural distal and proximal tremor, an electrode fitted with four points of contact was introduced within the entire height of the VIM. In each patient, stimulation of the lower part of the VIM was most effective in the distal component of the tremor, whereas its proximal component was specifically reduced by stimulation of its upper part. These results indicate that (1) proximal postural tremors can be as much affected by stimulation of the VIM as distal tremors, (2) there is a somatotopy in the VIM that is similar to that in the nucleus ventralis posterolateralis thalami, and (3) it is possible with this technique to adjust the VIM stimulation site so as to obtain the maximum efficacy according to the locale of the tremor. PMID- 8489407 TI - Hemispheric differences in layer III pyramidal neurons of the anterior language area. AB - OBJECTIVE: The major objective of this study was to determine if the lateralization of motor speech functions may be associated with hemispheric differences in the size of layer III pyramidal neurons in Brodmann's area 45. DESIGN: A case series design involving postmortem human specimens was used to compare the cross-sectional area of NissI-stained layer III pyramidal neurons of Brodmann's area 45 from the left and right hemispheres. SUBJECTS: A convenience sample consisting of seven cases with no known neurological or psychiatric disorders was obtained at autopsy. MAIN OUTCOME MEASURES: The cross-sectional area of layer III pyramidal neurons in both left and right hemispheres was measured in four fields per hemisphere per brain using a computerized image analysis system. Measurements of both the largest layer III pyramids and of all layer III pyramids were done. RESULTS: The largest layer III pyramidal neurons of area 45 were significantly larger in the left than in the right hemisphere in both an unblinded and a blinded series of measurements. However, this hemispheric difference appeared to be restricted to the largest neurons, since the mean size of all layer III pyramids in this area was not significantly different in the left and right hemispheres. CONCLUSIONS: The presence of a unique population of large pyramidal neurons in left Brodmann's area 45 may be related to the involvement of this region in the circuitry that mediates motor speech functions. PMID- 8489408 TI - Imaging of D2 dopamine receptors of patients with Parkinson's disease using single photon emission computed tomography and iodobenzamide I 123. AB - OBJECTIVE: To test the usefulness of single photon emission computed tomography (SPECT) with iodobenzamide in imaging basal ganglia and to elucidate the postulated upward regulation of the striatal D2 dopamine receptors in patients with early Parkinson's disease. DESIGN: Fourteen patients with Parkinson's disease and eight control subjects were investigated with SPECT using iodobenzamide labeled with iodine 123 as dopamine receptor ligand. SETTING: Neurological outpatient service at a university hospital in Kuopio, Finland. PATIENTS: Fourteen patients with recently diagnosed unilateral, unmedicated Parkinson's disease and eight healthy control subjects. RESULTS: The SPECT images revealed high uptake of iodobenzamide in the basal ganglia. In the patient group, the accumulation was more intense and the iodobenzamide affinity rate was significantly higher in the striatum contralateral to the parkinsonian symptoms. Also, the basal ganglia-cerebellum ratio was higher in the contralateral hemisphere. In the control group, no significant side-to-side differences were observed. CONCLUSION: Iodobenzamide with SPECT imaging is useful in evaluating patients with Parkinson's disease. The results also suggest compensatory D2 dopamine receptor upward regulation in the striatum of patients with early unmedicated Parkinson's disease. PMID- 8489409 TI - Multiple system atrophy and progressive supranuclear palsy. Diminished striatal D2 dopamine receptor activity demonstrated by 123I-IBZM single photon emission computed tomography. AB - OBJECTIVE: To measure D2 dopamine receptors in the striatum in patients with multiple system atrophy and progressive supranuclear palsy by I 3-iodo-6 methoxybenzamide labeled with iodine I 123 (123I-IBZM) single photon emission computed tomography and differentiate them from control subjects. DESIGN: Survey with the following as retrospective criterion standards: (1) parkinsonism, (2) negative apomorphine test, and (3) no or only slight reaction to dopaminergic medication. SETTING: Ambulatory or hospitalized care in an academic referral center. PATIENTS AND CONTROL SUBJECTS: Twenty-one patients with parkinsonism not responding to dopaminergic medication (17 with multiple system atrophy and four with progressive supranuclear palsy) and 21 control subjects without parkinsonism. INTERVENTION: In vivo imaging by single photon emission computed tomography using the D2 dopamine receptor specific radioligand 123I-IBZM. MAIN OUTCOME MEASURE: Striatum/occipital cortex ratio of count rate density as semiquantitative measurement for striatal D2 dopamine receptor density. RESULTS: A highly significant loss of striatal uptake of 123I-IBZM was observed in the patients in comparison to the control subjects with little or no overlap between values. CONCLUSIONS: The hypothesized loss of D2 receptors in multiple system atrophy has been confirmed. Use of 123I-IBZM single photon emission computed tomography may be a cost-effective alternative to positron emission tomography in the differential diagnosis of parkinsonism and in the selection of patients for dopaminergic therapy. PMID- 8489410 TI - Transverse myelitis. Retrospective analysis of 33 cases, with differentiation of cases associated with multiple sclerosis and parainfectious events. AB - OBJECTIVE: A study was undertaken to determine whether cases of parainfectious associated transverse myelitis (TM) and multiple sclerosis-associated TM could be distinguished on the basis of clinical criteria, radiologic features, or cerebrospinal fluid examination. A secondary objective was to determine the incidence of TM in a US population. DESIGN: A retrospective analysis of 33 cases was conducted. Cases were classified as being related to parainfectious multiple sclerosis, or spinal cord ischemia, or idiopathic. SETTING: All cases occurring in the Albuquerque, NM, area from 1960 through 1990 were reviewed. The population base was 500,000. OUTCOME MEASURES: Clinical presentation, radiologic features, cerebrospinal fluid, recovery of ambulation and bladder function, and recurrence rates were compared. RESULTS: Thirty-three patients satisfied study criteria, corresponding to an incidence of 4.6 per million per year. Forty-five percent of these cases were categorized as parainfectious, 21% as associated with multiple sclerosis, 12% as associated with spinal cord ischemia, and 21% as idiopathic. Patients with parainfectious TM suffered from spinal shock more frequently than did those with multiple sclerosis-associated TM. Patients with parainfectious TM showed evidence of spinal cord swelling, whereas patients with multiple sclerosis associated TM had spinal cord plaques on magnetic resonance images but none showed swelling. Oligoclonal bands were absent in patients with parainfectious TM and present in three of five patients with multiple sclerosis-associated TM. CONCLUSIONS: Parainfectious TM may be distinguishable from that associated with multiple sclerosis on the basis of presentation, findings on imaging, and the presence of cerebrospinal fluid oligoclonal bands. PMID- 8489411 TI - Leber's hereditary optic neuropathy. New genetic considerations. AB - OBJECTIVE: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease that causes bilateral central visual loss, predominantly in young men. Recently, this disorder has been associated with point mutations in the mitochondrial genome. The clinical characteristics of LHON are reviewed with special attention to recent advances in mitochondrial genetics. DATA SOURCES: Literature from the mid-19th century to the present is reviewed. STUDY SELECTION: Major review articles that include multiple large pedigrees in their analysis are featured. Special emphasis is placed on the recent reports on mitochondrial DNA abnormalities associated with this disease. DATA EXTRACTION: The older literature is reviewed critically with an understanding that some of the patients included as examples of LHON may have had a different disease. The more current references are assessed in regard to their inclusion of appropriate and complete mitochondrial DNA analysis. DATA SYNTHESIS: Leber's hereditary optic neuropathy, a maternally inherited disease primarily of young men, results in bilateral, acute or subacute, central visual loss and, ultimately, optic atrophy. Point mutations in the mitochondrial genes encoding proteins essential to oxidative phosphorylation have been associated with this disorder. Primary mutations include those found at positions 11778, 3460, and, possibly, 15257 and 14484. Mitochondrial, nuclear, and environmental factors may modify phenotypic expression. CONCLUSION: Genetic analysis has allowed for a broader view of what constitutes the clinical phenotype of LHON. PMID- 8489412 TI - Dental arch asymmetry in young healthy human subjects evaluated by Euclidean distance matrix analysis. AB - Form differences between biological structures can be evaluated using several approaches. A recently proposed method (Euclidean distance matrix analysis; EDMA) seems to be able to differentiate between size and shape differences. Here it has been applied to study the asymmetry of mandibular and maxillary arches in 50 men and 45 women with sound dentitions. The centres of gravity (centroids) of the occlusal surfaces of all permanent teeth (right second molar to left second molar) were individualized on the dental casts of subjects. The form of the right and left maxillary and mandibular hemi-arches was separately assessed by calculating all the possible linear distances between pairs of teeth within arch and side. Side differences were tested by EDMA. In men, the maxillary and the mandibular arches were both symmetrical (i.e. there were no significant differences in size or shape between the left and right hemi-arches). In women, the mandibular arch was symmetrical, but in the maxillary arch the two antimeres had a significantly different shape. No size differences were found between the left and right female hemi-arches. PMID- 8489413 TI - Human jaw-elevator muscle activity and food comminution in the dentate and edentulous state. AB - Masseter and temporal surface electromyograms were obtained from seven dentate subjects and six complete-denture wearers during mastication, maximal voluntary clenching and measurements of bite force. The participants chewed two artificial test foods with different textures. The dentate subjects comminuted both foods much better than the denture wearers. In both groups, the softer food was comminuted better than the firmer food. The differences in particle-size reduction originated largely from differences in the numbers of particles fragmented per chewing stroke. The rhythm of mandibular movement was unaffected by food texture and dental state. No significant differences in the duration of bursts of electric muscle activity were found between either group. Peak amplitudes of activity during mastication and maximal voluntary clenching were more than twice as large in the dentate subjects as in the denture wearers. In both groups, chewing the softer food was associated with lower peaks of activity than with the firmer food. The peak amplitudes were weakly related to the reduction in particle size. In both groups, the peak forces determined from electromyographic activity were larger than the estimated forces required for fragmenting the particles between the teeth. PMID- 8489414 TI - A bromodeoxyuridine immunocytochemical and morphometric study of the influence of growth hormone on cell proliferation in odontogenic mesenchyme of the Lewis dwarf rat. AB - Cell proliferation was studied in pre-odontoblasts, and in cells of the dental papilla and lingual dental follicle using bromodeoxyuridine immunocytochemistry and morphometry in Bouin's perfused and paraffin-embedded, undemineralized maxillary incisors. Cells in DNA synthesis, as shown by this technique, or in mitosis, were counted. Significantly fewer labelled nuclei, unlabelled nuclei and total nuclei were found in the tissues of growth hormone-deficient dwarf rats than in normal tissues. However, in dwarf rats treated for 6 days with bovine growth hormone, their numbers were equivalent to, or in some instances greater than those in normal tissues. The bromodeoxyuridine labelling index, the ratio of positive to negative nuclei and the mitotic index of pre-odontoblasts in dwarf rats were consistently lower than in normal rats, and were reversible by growth hormone. Growth hormone thus plays a part in odontogenic mesenchymal proliferation. PMID- 8489415 TI - Measurement of mandibular bone density ex vivo and in vivo by dual-energy X-ray absorptiometry. AB - Severe bone resorption is a vexing clinical problem, especially in patients without teeth. To study resorption in vivo, measurements of bone mineral density (BMD) of the mandible of both patients with and without teeth are needed. Using a Hologic QDR-1000 bone densitometer designed to measure lumbar spine and hips, ex vivo and in vivo measurements were made in selected areas of the mandible. The mandible was positioned such that the X-ray beam was perpendicular to its sagittal plane. In this way the beam hits first one half of the mandible and then the other. The reproducibility--expressed as coefficient of variation--of the ex vivo measurements was 0.5%. For in vivo measurements this coefficient was 3%. The method used for mandibular BMD would make it possible to define an average BMD in several categories of the normal population and of patients, and to compare bone density in the mandible with that in the axial and perpendicular skeleton. Improvement may be obtained by repeating the measurement. The entrance dose per scan is low, equalling that of one bitewing/radiograph. PMID- 8489416 TI - Simple reaction-time responses to mechanical and electrical stimuli in human masseter muscle. AB - The latencies of the simple reaction-time responses for opening and closing of the jaws in response to taps and pushes on teeth and lip shocks were measured in human adults. The reaction times were scored from both the integrated electromyographic (EMG) signal in individual trials, and from the cumulative sum (CUSUM) of the averaged EMG response to 50 stimuli. The mean reaction times for both closing and opening were about 80-90 ms for taps and electrical lip shocks, and about 140 ms for push, measured from the CUSUMs. The reaction times in individual trials were difficult to measure from the EMG signal because of the unsteady baseline. In contrast, the reaction times measured from the CUSUMs were clearly defined by the point at which the record began to move sharply above or below the baseline. However, because of the delays inherent in the CUSUM procedure, they were systematically longer than the means of the trial-by-trial measurements. PMID- 8489417 TI - Modelling relative masseter force from surface electromyograms during mastication in non-human primates. AB - The purpose was to analyse the relation between masseter electromyograms (EMGs) and relative masseter force during the power stroke of mastication. The electromyographic activity of the masseter was characterized by recording from bipolar surface electrodes placed over the superficial portion of the muscle; relative masseter force was estimated by characterizing surface bone strain along the lateral aspect of the zygomatic arch. The subjects were six adult macaques and one adult baboon. Masseter EMGs were quantified by r.m.s. analysis of the raw digitized EMG. The length of the time interval (the time constant) during which the r.m.s. values were calculated was repeatedly altered so as to determine which time constant was optimal for producing an EMG-derived waveform that best mimicked relative masseter force during the near-isometric phase of muscle contraction. The data indicate that between subjects this time constant varied from 35 to 72 ms, with an overall median of 42 ms and a grand mean of 49 ms. The use of a 42-ms time constant for all of the subjects resulted in an average latency between the masseter EMG waveform and relative masseter force of about 30 ms during the latter portion of the power stroke of mastication. This analysis provides, as a first approximation, an empirical basis for modelling relative jaw muscle force using surface EMGs recorded during that portion of the power stroke of mastication when the jaw-closing muscles are contracting under near isometric conditions. PMID- 8489418 TI - Bone sialoprotein in developing porcine dental tissues: cellular expression and comparison of tissue localization with osteopontin and osteonectin. AB - Bone sialoprotein (BSP) is a highly sulphated and glycosylated phosphoprotein that is a major constituent of bone and other mineralized connective tissues. Although BSP can mediate cell attachment through an RGD sequence and binds selectively to hydroxyapatite, its precise function in mineralized tissues is unknown. To provide insights into its possible function, affinity-purified polyclonal antibodies directed against porcine BSP were used to demonstrate the histological distribution of this protein in developing porcine mandibular alveolar bone and the associated tooth tissues from 35- and 50-day fetuses. In addition, a porcine cRNA probe was used to determine the cellular expression of BSP in the same tissues by in situ hybridization. Immunoreactivity to BSP protein was restricted to the cells and matrix of the mineralized tissues of alveolar bone and dentine. In dentine, BSP was localized to the odontoblasts and their processes and to the peritubular dentine. In the alveolar bone, immunoreactivity for BSP was evident in osteoblastic cells and osteocytes and in the bone matrix; the older bone stained more strongly than newly formed bone. In addition, BSP appeared to be concentrated in the reversal lines of the rapidly remodelling bone. The distribution of BSP in these tissues revealed distinct differences when compared to osteopontin and SPARC/osteonectin, which are also prominent non collagenous proteins of mineralized tissues. Most notable was the localization of osteopontin and especially osteonectin in non-mineralizing tissues. The immunoreactivity of osteoblasts and osteocytes for BSP in bone was consistent with the high levels of BSP mRNA revealed by in situ hybridization. However, much lower levels of hybridization were evident in the odontoblasts of developing mandibular molars. These studies demonstrate that BSP is expressed during the early formation of dentine and alveolar bone and that the protein accumulates in the peritubular dentine and bone matrix. PMID- 8489419 TI - Effect of the bathing fluid on measurements of diffusion in dental plaque. AB - The suggestion that loss of labile components from dental plaque into contacting aqueous buffer during some diffusion measurements might change the plaque's diffusion behaviour, and therefore invalidate the results, has been tested using tracer clearance. (a) Diffusion of [14C]-acetate and 3H2O was determined before and after a 3-4 h equilibration with neutral buffer. No differences or trends were found. (b) Mean normalized [14C]-acetate clearance curves from live plaque for measurements before and after such equilibration were identical in shape and showed no change in diffusion coefficient during clearance, as evidenced by their fits to the theoretical clearance curve. No significant difference was found between coefficients for the two periods (paired sample test). In addition, [14C] lactate and 3H2O were found to permeate plaque in a miniature diaphragm diffusion cell at rates independent of whether the plaque was bathed either in saliva supernatant, plaque fluid or neutral buffer. This lent some further support to the main findings. It is concluded that diffusion through dental plaque is little affected by the bathing fluid. PMID- 8489420 TI - The effect of four jaw relations on electromyographic activity in human masticatory muscles. AB - Significant differences were found in the electromyographic (EMG) activation between the masseter and temporalis muscles for the leaf gauge (LG), manually manipulated (CR) and neuromuscular (NM) bite positions during maximal static clench. The LG position consistently demonstrated the lowest EMG activity, while the NM position displayed the highest degree of muscle activity. Similarly, the ratio of the masseter/temporalis EMG activity during maximal clench was lower for the LG and CR positions and highest for the NM position. These data indicate that the NM position produced the greatest total muscle recruitment, with more masseter involvement during maximal clench, and enabled the subjects to generate greater clenching forces in the NM position as compared to the LG and CR positions. PMID- 8489421 TI - The microscopic structure and function of the vascular retrodiscal pad of the human temporomandibular joint. AB - The highly vascular retrodiscal pad attaches the articular disc of the temporomandibular joint to osseous structures posterior to it. There is debate as to whether or not the pad includes erectile tissue. Histological examination of 11 retrodiscal pads revealed thick-walled muscular arteries, thin-walled veins and numerous vascular sinuses, which is different from the erectile tissue of the corpora cavernosa. Its histological features and position within the joint suggest that the retrodiscal pad may function differently from other human joints due to: (1) the large amount of distraction it undergoes relative to its size and (2) its location anterior to the ear. PMID- 8489422 TI - Evidence for endothelial junctions acting as a fluid flux pathway in tensioned periodontal ligament. AB - A continuous tension load of 1.0 N applied to the rat maxillary first molar for 30 min led to a significant increase (p < 0.05) in the mean number of junctions/microns of endothelial perimeter. The mean number of junctions/microns was compared with the mean number of tissue channels/microns 2 as previously reported by fitting linear and quadratic equations. An increase in the mean number of junctions/microns was associated with an increase in mean number of tissue channels/microns 2 (p < 0.01) in control and experimental periodontal ligament. Significant increases in the mean number of junctions/microns occurred in the middle-third zone for venous capillaries (p < 0.01) and in the tooth-third zone for postcapillary-sized venules (p < 0.001). It is concluded that the endothelial junctions of venous capillaries and postcapillary-sized venules provide significant pathways for fluid transport across the tensioned walls of the microvascular bed of the periodontal ligament. PMID- 8489423 TI - Can cataract surgery be marketed like hamburgers in developing countries? PMID- 8489424 TI - Effect of continuous circular capsulorhexis and intraocular lens fixation on the blood-aqueous barrier. PMID- 8489425 TI - Corneal bifocal effects by laser photorefractive keratectomy. PMID- 8489426 TI - Statistical analysis for method comparison data. PMID- 8489427 TI - An unexpected problem with an inexpensive air pump for vitreous surgery. PMID- 8489428 TI - Diabetes-like preproliferative retinal changes in galactose-fed dogs. PMID- 8489429 TI - Intracameral tissue plasminogen activator in neovascular glaucoma. PMID- 8489430 TI - Aneurysmal bone cyst of the orbit and ethmoid sinus. PMID- 8489432 TI - DHHS cataract guidelines released. PMID- 8489431 TI - Sweet's syndrome presenting as conjunctivitis. PMID- 8489433 TI - Guidelines. Cataract surgery and beyond. PMID- 8489434 TI - The treatment of pediatric retinal detachment. PMID- 8489435 TI - The 25th anniversary of the National Eye Institute. PMID- 8489436 TI - Standard for clinical electro-oculography. International Society for Clinical Electrophysiology of Vision. AB - The electro-oculogram is a widely used electrophysiological test, but recording techniques vary among different laboratories. This standard, approved by the International Society for Clinical Electrophysiology of Vision (ISCEV), describes simple technical procedures that will allow reproducible and comparable electro oculograms to be recorded under a few defined conditions. The document is intended to improve the comparability of electro-oculographic data obtained throughout the world by guiding both clinicians and manufacturers, and the ISCEV recommends that future published reports indicate whether the recording technique meets the international standard. PMID- 8489437 TI - Accuracy of coding in Medicare part B claims. Cataract as a case study. AB - We studied the accuracy of Medicare part B coding for cataract extraction to provide validation for research involving Medicare data. Hospital and physician office records associated with a sample of 802 paid claims for cataract surgery were reviewed. The sample was randomly selected from 118,420 Medicare part B claims for cataract surgery submitted by physicians in an 11-state sample during the first quarter of 1988. Medical records were successfully obtained for 796 cataract surgery episodes (99.2%), of which 794 (99.7%) indicated that cataract extraction had been performed. In the remaining two cases, cataract surgery was attempted but aborted. In 24 (3%) of the 794 cases, the surgical approach (intracapsular or extracapsular) indicated in the operative note differed from the coded on the physician's bill. In all cases in which the operative note indicated a secondary procedure performed at the time of surgery, the billing information was in agreement. We conclude that, at least in the case of cataract surgery, the Medicare part B database is 99% accurate (95% confidence interval, +/- 0.6%) for cataract surgery having occurred and 96% accurate (95% confidence interval, +/- 1.4%) in terms of surgical approach. PMID- 8489438 TI - Sub-pigment epithelial membranes after photocoagulation for diabetic macular edema. AB - OBJECTIVE: The chronic histopathologic effects of focal and grid argon laser photocoagulation were examined in eyes obtained at autopsy that had previously been treated for diabetic macular edema. The focus was on further characterizing fibrous sub-pigment epithelial membranes that previously had been shown to extend beyond burn edges. DESIGN: A total of 131 argon laser burns were evaluated in five eyes. Tissue was embedded in paraffin or glycol methacrylate, serially sectioned, and examined by light microscopy. MAIN OUTCOME MEASURE: Outer and inner nuclear layer defects were measured, and the frequency and extent of sub pigment epithelial membranes was estimated. The presence of Muller cell processes among membranes was evaluated by immunostaining for glial fibrillary acidic protein and enzyme histochemical staining for carbonic anhydrase. RESULTS: Burns consistently produced defects in the outer nuclear layer that were larger than the spot size of the laser beam. Inner nuclear layer defects were present in only seven of 131 burns. Glycol methacrylate--embedded tissue sections from 73 burns showed sub-pigment epithelial membranes in all five eyes. In one eye, membranes were confluent between burns. In the remaining four eyes, 37 individual membranes were found among 53 burns, and 47% of membranes contained Muller cell processes. The membranes in paraffin-embedded tissue could not be adequately evaluated. CONCLUSIONS: After focal laser treatment for diabetic macular edema, the inner retina was usually spared. Fibrous sub-pigment epithelial membranes were frequent among burns in all five eyes, and they showed a conspicuous contribution by Muller cell processes. We speculate that by impairing the overlying pigment epithelium, these membranes may contribute to a progressive enlargement of laser scars. PMID- 8489439 TI - Retinal detachments in incontinentia pigmenti. AB - We report on retinal detachments in six eyes of four patients with incontinentia pigmenti. These nonrhegmatogenous traction retinal detachments are characterized by extensive preretinal and vitreous fibrous organization that pull the retina anteriorly behind the lens. The clinical course and fundus appearance of the retinal detachments, beginning with the avascular peripheral retina and leading to traction retinal detachment, are similar to those of cicatricial retinopathy of prematurity. Vitreous surgery was performed on three eyes (two patients), with partial reattachment of a total retinal detachment in one eye and complete reattachment of a partial retinal detachment in a second eye. These cases represent the first successful surgical interventions reported for retinal detachment in incontinentia pigmenti. PMID- 8489440 TI - Surfactant prophylaxis and retinopathy of prematurity. AB - OBJECTIVE: The use of exogenous surfactant has led to a decrease in mortality of low-birth-weight infants. In some instances, use of this drug has also led to a reduction in neonatal morbidity, such as respiratory distress syndrome. This study was undertaken to determine whether prophylactic surfactant therapy has an effect on the incidence and severity of retinopathy of prematurity. DESIGN: The authors reviewed the findings of sequential prospective ophthalmologic examinations performed in two neonatal intensive care units that participated in randomized trials of prophylactic exogenous mammalian surfactant. PATIENTS: There were 43 patients in the control group (no prophylactic surfactant) and 43 patients in the prophylactic surfactant group. These groups did not differ on the basis of birth weight, gestational age, race, or gender. RESULTS: The incidence and severity of retinopathy of prematurity did not vary between the control and surfactant-treated infants. Only birth weight appeared to be significantly related to the incidence and severity of retinopathy of prematurity. CONCLUSIONS: These results suggest that the widespread use of prophylactic surfactant therapy will not change the incidence of retinopathy of prematurity in extremely low birth-weight infants. However, the absolute number of affected patients will likely increase because of the decrease in mortality of extremely low-birth weight patients, the patients most at risk for retinopathy of prematurity. PMID- 8489441 TI - Posterior retinal folds following vitreoretinal surgery. AB - The authors conducted a retrospective review of 32 patients with posterior retinal folds following retinal reattachment surgery. Twenty-eight of these patients underwent combined pars plana vitrectomy, fluid-air exchange with either internal drainage through a preexisting retinal break or external drainage of subretinal fluid, and scleral buckle. We believe these drainage techniques resulted in incomplete elimination of subretinal fluid, with resultant sequestration of fluid at the dependent border between attached and detached retina. Metamorphopsia and decreased visual acuity were noted in patients with folds involving the macula. The likelihood of fold formation may be greatly reduced by internal drainage through a posterior retinotomy combined with more complete removal of slowly gravitating fluid as it flows dependently to the drainage site. PMID- 8489442 TI - Atypical presentations of macular holes. AB - OBJECTIVE: To describe nine cases of macular holes with atypical presentations and propose possible mechanistic explanations. SETTING: The steps leading to typical idiopathic macular hole formation have recently been defined. PATIENTS: Patients included seven with previous retinal detachment and subsequent macular hole formation and two with macular hole formation after vitrectomy for epiretinal membrane removal. CONCLUSIONS: The occurrence of these cases may seem to contradict reported pathogenesis schemes, but they are explainable within reported grading schemes. PMID- 8489443 TI - Long-term effectiveness of optic nerve sheath decompression for pseudotumor cerebri. AB - OBJECTIVE: To determine the long-term success of optic nerve sheath decompression in preserving visual function in patients with pseudotumor cerebri (PTC). DESIGN: To define stability of visual fields, we reviewed 32 series of postoperative visual fields in patients who were undergoing optic nerve sheath decompression for PTC who had stable visual acuity and four or more fields during 6 to 60 months of follow-up. The SD of these series was 0.80 dB (+/- 0.39 dB) of mean deviation. Fluctuations within 2 SDs of the 1-month postoperative field were +/- 1.60 dB. We therefore defined stability as a mean deviation within 2 dB of the preoperative visual field; improvement, greater than 2-dB mean deviation, and worsening, less than 2-dB mean deviation. We then extended our review to include all patients (54 patients, 75 eyes) who underwent optic nerve sheath decompression for PTC, who were followed up with serial automated perimetry (Humphrey 30-2). RESULTS: Fifty-one eyes (68%) showed improvement (36%) or stabilization (32%) of visual function. Twenty-four eyes (32%) experienced deterioration of visual function after an initially successful optic nerve sheath decompression. The probability of failure from 3 to 5 years was .35 by life-table analysis. CONCLUSION: Optic nerve sheath decompression effectively stabilizes or improves visual function in the majority of patients with PTC and visual loss. However, it may fail at any time after surgery. Patients with PTC need to be followed up routinely with automated perimetry to detect deterioration of visual function. PMID- 8489444 TI - Effect of repetitive imaging on topographic measurements of the optic nerve head. AB - OBJECTIVE: A confocal scanning diode laser ophthalmoscope was used to determine the number of examinations needed to obtain highly reproducible topographic measurements of the optic nerve head and peripapillary retina. DESIGN: Topographic images of the optic nerve head and peripapillary retina were obtained in one randomly selected eye on five separate visits. On each occasion the selected eye had five examinations. For each examination, one image was acquired (a total of 25 images per eye). Reproducibility was calculated as the average SD of all image elements (65,536 pixels). SETTING: Glaucoma referral center. SUBJECTS: Five normal subjects and five patients with glaucoma. INTERVENTION: Topographic imaging of the optic nerve head and peripapillary retina. MAIN OUTCOME MEASURE: Number of examinations needed to obtain highly reproducible topographic measurements. RESULTS: In healthy subjects, reproducibility with one examination per visit was 35.5 microns; this improved to 25.7 microns with three examinations and 22.5 microns with five examinations. In older patients with glaucoma, the reproducibility improved from 40.2 microns with one examination per visit to 28.5 and 24.1 microns with three and five examinations, respectively. CONCLUSION: We recommend a series of three examinations to provide high reproducibility with optimal efficiency in terms of time and materials used. PMID- 8489445 TI - Comparison of the Farnsworth-Munsell 100-Hue, the Farnsworth D-15, and the L'Anthony D-15 desaturated color tests. AB - OBJECTIVE: The Farnsworth-Munsell 100-Hue, the Farnsworth D-15, and the L'Anthony D-15 desaturated color tests were administered to patients with glaucoma to determine whether the D-15 or D-15 desaturated color tests could be used to predict performance on the 100-Hue test in clinical populations. METHODS: The three color tests were administered to 35 patients with glaucoma. The results were analyzed using the method of Vingrys and King-Smith that calculates an angle (type of color loss) score, S-index (measure of the randomness of cap arrangement), and a C-index (a measure of the severity of color loss) based on the cap arrangement. RESULTS: The 100-Hue error score was significantly related to the D-15 and D-15 desaturated C-indexes. Furthermore, the 100-Hue S-index could be predicted from the D-15 or D-15 desaturated S-indexes. The 100-Hue angle could not be predicted from the D-15 or D-15 desaturated color tests. CONCLUSIONS: The D-15 desaturated color test (which requires significantly less time to administer) may be used to assess the severity of color vision deficit in some patient populations. PMID- 8489446 TI - Transbronchial lung biopsy in the diagnosis of suspected ocular sarcoidosis. AB - We conducted clinical research using transbronchial lung biopsy in 60 patients with suspected ocular sarcoidosis who showed no bilateral hilar lymphadenopathy and sparse contributory evidence for sarcoidosis. The patients had a combination of granulomatous iritis with mutton-fat keratic precipitates or iris nodules, trabecular nodules, tent-like peripheral anterior synechiae, snowball or string of-pearls vitreous opacities, retinal perivasculitis, and spotty retinochoroidal exudates. The transbronchial lung biopsy specimen showed noncaseating epithelioid granuloma in 37 patients (61.7%); these patients were diagnosed as having sarcoidosis. Bronchoalveolar lavage showed a high percentage of patients with an increased lymphocyte fraction among those with positive transbronchial lung biopsy results. The present results may serve as a basis for a clinical diagnosis of sarcoidosis in patients with suspected sarcoidosis without apparent extraocular manifestations. PMID- 8489447 TI - Blue-on-yellow perimetry can predict the development of glaucomatous visual field loss. AB - OBJECTIVE: The purpose of this investigation was to determine whether blue-on yellow (B/Y) perimetry is capable of predicting the onset and location of impending glaucomatous visual field loss in patients with ocular hypertension. DESIGN: A Humphrey Field Analyzer (Humphrey Instruments, San Leandro, Calif) was modified to perform B/Y perimetry to isolate and measure the sensitivity of short wavelength-sensitive mechanisms. Participants were tested annually with standard white-on-white (W/W) and B/Y automated perimetry for a period of 5 years. PATIENTS: The study population consisted of 38 patients with ocular hypertension and 62 age-matched normal control subjects. RESULTS: Initially, all 76 ocular hypertensive eyes had normal W/W automated perimetry results, with 67 eyes having normal and nine eyes having abnormal B/Y test results. Five years later, five of the nine ocular hypertensive eyes with initial B/Y abnormal results developed glaucomatous visual field loss measured by standard W/W automated perimetry, while none of the 67 ocular hypertensive eyes with initially normal B/Y results developed abnormal W/W perimetry results. CONCLUSIONS: Blue-on-yellow perimetry deficits are an early indicator of glaucomatous damage and are predictive of impending glaucomatous visual field loss for standard W/W automated perimetry. To our knowledge, this is the first prospective, long-term longitudinal study that demonstrates the ability to predict the onset of glaucomatous visual field loss in patients with ocular hypertension on the basis of psychophysical testing. PMID- 8489448 TI - Progression of early glaucomatous visual field loss as detected by blue-on-yellow and standard white-on-white automated perimetry. AB - OBJECTIVE: To determine whether blue-on-yellow perimetry reveals progression of glaucomatous damage before it is evident with standard white-on-white perimetry. DESIGN: A Humphrey field analyzer (Humphrey Instruments, San Leandro, Calif) was modified to perform blue-on-yellow perimetry to isolate and measure the sensitivity of short wavelength-sensitive mechanisms. Participants were tested annually with standard white-on-white automated perimetry and blue-on-yellow automated perimetry for 5 years. PATIENTS: Sixteen patients with early glaucomatous visual field loss in one or both eyes and 62 age-matched normal control subjects. RESULTS: At baseline, 25 (78.1%) of the 32 eyes exhibited larger deficits with blue-on-yellow perimetry, five (15.6%) had equivalent loss with both tests, and two (6.3%) had larger deficits with standard white-on-white perimetry. Seven (21.9%) of the 32 eyes demonstrated evidence of progressive visual field loss with standard white-on-white perimetry in 5 years, while the other 25 eyes (78.1%) were relatively stable. Deficits with blue-on-yellow perimetry were twice as large as deficits with white-on-white perimetry in the stable group and were three to four times as large in the group with progressive field loss. CONCLUSIONS: Blue-on-yellow perimetry is effective in predicting which patients with early glaucomatous visual field loss are most likely to have progressive loss. The rate of progressive loss is greater with blue-on-yellow perimetry than with standard white-on-white perimetry. PMID- 8489449 TI - Maintained intraocular pressure reduction with once-a-day application of a new prostaglandin F2 alpha analogue (PhXA41). An in-hospital, placebo-controlled study. AB - To eliminate uncertainties about compliance, 15 patients with glaucoma (intraocular pressure [IOP] > 22 mm Hg and < 40 mm Hg) were hospitalized to participate in a clinical trial of the ocular hypotensive effectiveness of the new prostaglandin F2 alpha analogue prodrug, PhXA41 (13,14-dihydro-17-phenyl-18, 19, 20-trinor-PGF2a-isopropyl ester; latanoprost [World Health Organization generic name]). At 9 PM on each of five consecutive days, one of the investigators applied one drop of a 0.006% solution of PhXA41 (representing approximately 2 micrograms of PhXA41 per treatment) to one eye of nine patients and one drop of placebo to one eye of six patients. This was followed by an evaluation of potential local side effects at 9:30 PM. Complete examinations, including tonometry (Goldmann), were also performed at 8 AM and 8 PM on days 1 to 6, as well as at noon and 4 PM on days 1, 2, and 6. Except for mild conjunctival hyperemia in two PhXA41-treated eyes (once each at 8 AM), no side effects were observed or reported by any patient. Starting with the first IOP measurement after the first treatment (8 AM on day 2), IOP was reduced by 20% to 30% in the eyes treated with PhXA41. This reduction was highly significant (P < .01 at 12 time points and P < .05 at the remaining two measurements) throughout the study. The IOP reduction did not become attenuated during the 23 hours after treatments. At 11 hours after the last treatment, the mean (+/- SD) IOP difference between PhXA41-treated and contralateral control eyes was -5.5 +/- 2.8 mm Hg, as compared with -6.1 +/- 1.8 mm Hg 12 hours later. PhXA41 must, therefore, be regarded as an excellent candidate for use as a once-a-day glaucoma medication. PMID- 8489450 TI - Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. A study on patients with elevated intraocular pressure. AB - OBJECTIVE: To evaluate the effects of PhXA41, a new prostaglandin analogue, on the intraocular pressure (IOP) in patients receiving pilocarpine treatment and the effects of pilocarpine in patients receiving PhXA41 treatment. DESIGN: Twenty patients with ocular hypertension were randomized into two parallel groups. The treatment period was 2 weeks. Ten patients in group 1 were given PhXA41 twice daily during week 1 and, in addition, pilocarpine three times daily during week 2. Ten patients in group 2 received pilocarpine three times daily during week 1 and PhXA41 twice daily in addition during week 2. PhXA41 was used in a concentration of 0.006%, and pilocarpine was given in a concentration of 2%. MAIN OUTCOME MEASURES: In group 1, the mean IOP on day 0 was 25.1 mm Hg; on day 7, 19.1 mm Hg; and on day 14, 17.6 mm Hg. In group 2, the mean IOP on day 0 was 23.8 mm Hg; on day 7, 20.4 mm Hg; and on day 14, 17.7 mm Hg. RESULTS: PhXA41 had a clinically significant IOP-lowering effect (23.4% reduction on day 7 as compared with baseline day (P < .001). The corresponding value with pilocarpine was 14.3% (P < .001). When pilocarpine was added to PhXA41, the additional IOP reduction was 7.4% (P < .01) compared with 14.2% (P < .01) when PhXA41 was added to pilocarpine. The two groups were found to have an almost equal reduction in IOP on day 14 (group 1, 29.4%; group 2, 26.6%). No serious adverse reactions were seen. Some conjunctival hyperemia in the PhXA41-treated eyes was noted on day 7, as compared with the pilocarpine-treated eyes, but there were few complaints of discomfort. CONCLUSIONS: This study indicated that PhXA41 could be useful in the treatment of glaucoma, as monotherapy, or in certain cases in combination with pilocarpine. PMID- 8489451 TI - Corneal endothelial involvement in pseudoexfoliation syndrome. AB - Information on corneal manifestation in pseudoexfoliation syndrome is restricted to specular microscopic studies. We investigated morphologic changes of the posterior cornea of two corneal buttons with Fuchs' endothelial dystrophy obtained at penetrating keratoplasty and of one enucleated glaucomatous eye from three patients with ocular pseudoexfoliation syndrome. By transmission electron microscopy, large clumps of typical pseudoexfoliation material were found adhering to the corneal endothelium and masses of pseudoexfoliation material were incorporated into the posterior Descemet's membrane. In the affected areas, the endothelial layer appeared irregular and discontinuous, with loosely adherent, degenerating cells producing pseudoexfoliation fibers and fibroblastic cells spreading to cover denuded Descemet's membrane. The present findings indicate that the pseudoexfoliation material is initially formed by degenerative endothelial cells and that it becomes subsequently buried by overgrowing cells. The corneal endothelial involvement may potentiate complications of cataract surgery and open angle glaucoma in patients with pseudoexfoliation syndrome. PMID- 8489452 TI - Cataract and survival in an elderly nondiabetic population. AB - Follow-up ranging between 6 and 8 years of the survival of a cohort of 473 elderly nondiabetic subjects randomly selected from a small English town showed an age- and sex-adjusted association between nuclear cataract at the time of baseline examination and decreased survival (P = .002). Comparing those with and without nuclear cataract, the adjusted relative hazard for death was 1.52 (95% confidence interval, 1.15 to 1.99). This effect remained virtually unchanged when also adjusted for whether the subject reported ever having been a smoker. PMID- 8489453 TI - Vision change and quality of life in the elderly. Response to cataract surgery and treatment of other chronic ocular conditions. AB - OBJECTIVE: Evaluation of health care in older populations has increasingly focused on quality of life as a critical outcome of treatment. Vision is assumed to be central to functioning. Data suggest that aging, in itself, is associated with a decline in visual functioning, which, in turn, is related to a decline in physical and mental functioning. Other studies indicate that cataract surgery is followed by significant improvement in vision and visual function. Our objective was to test these assumptions. DESIGN: Prospective study of 1021 patients, consecutively drawn from 76 randomly selected ophthalmologists' offices in three cities. Structured interviews were completed at baseline, 2 months, and 1 year after entry. PATIENTS: Six hundred thirteen patients with cataracts and 408 other ophthalmic patients drawn from the same offices but treated for other chronic ocular disorders. All received refractive services as needed. SETTING: Patients from three cities (Baltimore, Md, St Louis, Mo, and San Diego, Calif) were interviewed once in their homes and twice by telephone. INTERVENTIONS: The study involved the measurement of the effects of usual treatment for cataracts and other degenerative eye diseases. MAJOR OUTCOME MEASURES: Visual, social, and psychological functioning. RESULTS: Within 1 year of treatment, change in visual function was accompanied by significant changes, in the same direction, in quality of life functions: night-time driving, daytime driving, community activities, home activities, mental health, and life satisfaction. In addition, the patients with cataracts showed significantly greater improvement in measures of vision than did the noncataract group. CONCLUSIONS: Regardless of treatment, improvement across quality of life functions occurred when visual function improved. Thus, many types of functional degeneration observed in older populations, attributed to a decline in vision, can be slowed, or even reversed, when visual function is improved. Cataract surgery was effective in improving vision and quality of life functions. PMID- 8489454 TI - Outcomes of cataract surgery. Improvement in visual acuity and subjective visual function after surgery in the first, second, and both eyes. AB - OBJECTIVE: No previous study documents improvement in visual acuity and subjective visual function associated with cataract surgery in the first eye, second eye, and both eyes. Measurement of subjective aspects of visual function and quality of life provides information that cannot be obtained with simple measurement of Snellen visual acuity. METHODS: From 76 ophthalmology practices in three cities, patients undergoing cataract extraction with intraocular lens implantation (n = 613) and comparison patients (n = 408) were enrolled in a prospective study. Questionnaires elicited visual function information before and after surgery, and visual acuity was obtained from the ophthalmologic record. RESULTS: Among patients with cataract and no other eye disease, baseline subjective visual function before surgery in the second eye was better than that before surgery in the first eye. Improvement in subjective visual function was approximately equal postoperatively in first and second eyes. Improvement in subjective function in both eyes postoperatively was significantly greater than that after surgery in the first eye or second eye alone. No statistically significant difference across surgical groups in the proportion of patients demonstrating improvement in visual acuity was observed. CONCLUSION: Patients who underwent surgery in both eyes reported greater improvement in subjective visual function than did those who underwent surgery in one eye. Thus, there seems to be a benefit associated with restoring binocular vision in this population. These findings support the policy recommendation that cataract surgery in both eyes remains the appropriate treatment for patients with bilateral, cataract-induced visual impairment. PMID- 8489455 TI - Comparison of laser phacovaporization using the Er-YAG and the Er-YSGG laser. AB - OBJECTIVE: To study the interaction of the erbium (Er)-YAG (2.94 microns) and the Er-YSGG (2.79 microns) lasers with the human crystalline lens tissue. METHODS: Fresh human crystalline lens sections were used to measure the photovaporization threshold, rate, and damage zone of the two lasers. RESULTS: We found the photovaporization threshold for the Er-YAG and the Er-YSGG lasers to be 1.4 J/cm2 and 5.5 J/cm2, respectively. At 10 J/cm2, the photovaporization rate is 67.9 microns per pulse for the Er-YAG laser and 18.4 microns per pulse for the Er-YSGG laser. The increased rate of photovaporization as a function of radiant energy for the Er-YAG laser is almost twice that for the Er-YSGG. Damage zones for the Er-YAG laser ranged from 4 to 9 microns compared with 10 to 22 microns for the Er YSGG. CONCLUSIONS: It is apparent that both lasers can adequately photovaporize human crystalline lens tissue and should be further studied for this purpose. PMID- 8489456 TI - Orbital varix. PMID- 8489457 TI - Ischemic hypertensive choroidopathy. Fluorescein angiography, indocyanine green videoangiography, and measurement of pulsatile blood flow. PMID- 8489458 TI - Posterior capsule tears during extracapsular cataract surgery in India. AB - We determined the incidence in a developing nation of posterior capsule rupture during planned extracapsular cataract surgery and insertion of a posterior chamber intraocular lens. The results, in part, determine whether this complication limits the widespread utility of this procedure in developing nations. We retrospectively reviewed charts of all patients undergoing planned extracapsular cataract surgery during a 6-month period; all patients received surgery as inpatients at the Aravind Eye Hospital, Madurai, India, and all were southern Indians. We tried to exclude most patients with prior ocular diseases associated with loss of zonular or posterior capsule integrity. One eye of all eligible patients was included. Extra-capsular cataract surgery was performed using manual irrigation and aspiration with the insertion of a posterior chamber intraocular lens. In this study, we evaluated the ability to maintain an intact posterior capsule with the insertion of a posterior chamber intraocular lens during surgery. Of 898 eyes operated on, 15 (1.7%) developed rents in the posterior capsule, and seven of these had vitreous in the anterior chamber. Nine of the 15 rents were in eyes with either traumatic or hypermature lenses. We conclude that even in a developing nation where many cataracts are mature, hypermature, or traumatic, extracapsular cataract surgery with the insertion of a posterior chamber intraocular lens is technically feasible if surgeons are skilled and experienced. PMID- 8489459 TI - Analysis of 20,119 deliveries in Dhaka Medical College Hospital. AB - Data of 20,119 deliveries in Dhaka Medical College Hospital are presented. Dhaka Medical College Hospital is the chief referral hospital in Dhaka city. The 15% of patient were 18 years of age or below and 18% were above 35 years of age or above. The 48.22% were primaegravida and 51.78% were multigravida, of these 28% were grandmultigravida. The 89% had no previous antenatal checkup. The 92.72% had cephalic presentation, 65.52% had normal vaginal delivery, 21.07% had caesarean section, 11.18% had forceps delivery. Perinatal mortality during hospital stay was 143/1,000 deliveries, maternal mortality 2,510/100,000, mainly due to eclampsia. Complications during delivery were mainly in the form of ruptured uterus (1.10%), P.P.H. (1.06%), and retained placenta (3.88%). PMID- 8489460 TI - Synchronous secretion of LH and prolactin during the normal menstrual cycle. AB - Integrated hourly concentrations of day-time prolactin and LH showed significant positive correlations (p < 0.05-0.001) on the day of the pre-ovulatory mid cycle LH surge (n = 3) and during the mid luteal phase (n = 6) in a group of regularly cyclic women. No correlations between these two hormones were seen during any other stage of the cycle. Consistent significant correlations were not evident between prolactin and oestradiol, prolactin and progesterone, LH and oestradiol or LH and progesterone during any other stage of the cycle. PMID- 8489461 TI - Changes of hemorheologic properties during normal human pregnancy. AB - To investigate alterations of hemorheologic properties during pregnancy, we measured the hematocrit (Hct) and fibrinogen levels, blood viscosity, and erythrocyte deformability in 10 healthy nonpregnant women and in 10 women with uncomplicated pregnancies. The Hct decreased during pregnancy, while the plasma fibrinogen concentration was elevated. No significant changes in blood viscosity were observed throughout pregnancy. Erythrocyte deformability was significantly decreased in pregnancy when compared to the nonpregnant state, but returned to the nonpregnant level by the 7th postpartum day. These findings suggest that adequate microcirculation is maintained in the uteroplacental unit during gestation by hemodilution, which prevents an elevation of blood viscosity despite the increase in fibrinogen and the decrease of erythrocyte deformability. These changes are thus thought to be among the physiological maternal adaptations to fetal growth and development. PMID- 8489462 TI - Combined examination of middle cerebral artery and umbilical artery flow velocity waveforms in growth-retarded fetuses. AB - The resistance index (RI) of middle cerebral artery (MCA) and umbilical artery (UA) flow velocity waveforms (FVWs) were characterized retrospectively in 60 growth-retarded fetuses in the third trimester of gestation. Reference ranges of MCA-RI, UA-RI, and the UA-RI/MCA-RI ratio to gestational age were obtained from a cross-sectional study of 150 healthy fetuses. Growth-retarded fetuses that developed fetal distress had lower MCA-RIs, higher UA-RIs, and higher UA-RI/MCA RI ratios than growth-retarded fetuses that had good outcomes. The highest sensitivity for fetal distress was observed in the UA-RI/MCA-RI ratio (UA-RI/MCA RI 94.1%, MCA-RI 79.4%, UA-RI 61.8%), and the highest specificity was in MCA-RI (MCA-RI 92.3%, UA-RI 84.6%, UA-RI/MCA-RI 76.9%). In growth-retarded fetuses, the combined examination of MCA FVWs and UA FVWs was more useful in assessing fetal well-being than examination of UA FVWs alone. PMID- 8489463 TI - Outcome of pregnancy in patients with organic heart disease in Taiwan. AB - A total of 122 pregnancies in 101 women with organic heart disease were reviewed. The incidence of organic heart disease in pregnant women was 0.25%. The ratio of rheumatic to congenital heart disease was 1.0 to 1.5. In the congenital heart disease group, IUGR was more frequent in the cyanotic group as were preterm births. Patients with cyanotic lesions had a significantly higher maternal mortality rate than those with acyanotic lesions. The cyanotic group without surgical correction had a significantly higher maternal mortality rate and more IUGR than those with correction. Congestive heart failure was the most common maternal complication, with a rate of 38.1%. The patients with good cardiac status control during pregnancy developed less IUGR, had fewer preterm births, less maternal morbidity and less maternal mortality than those in poor condition. Patients in functional classes I and II before pregnancy carried less risk of maternal morbidity than those in classes III and IV. PMID- 8489464 TI - A case of successful pregnancy and delivery after brain metastasis of choriocarcinoma. AB - This is report regarding a 28-year-old woman who conceived and delivered a healthy child following treatment for brain metastasis of choriocarcinoma in 1980 and a prolonged postoperative disease-free period. The patient had delivered a hydatidiform mole. Eight months afterwards she was admitted to our hospital with occipital pain, vomiting and stupor, and upon CT examination was found to have a brain tumor. The surgically removed tumor was pathologically diagnosed as choriocarcinoma. Postoperative methotrexate chemotherapy rapidly lowered the preoperative urinary human chorionic gonadotrophin (19 IU/ml), and allowed restoration of the preoperative LH level, consciousness, ambulation, and manifest ovulation. Occasional mild cramps were received by continuous use of anticonvulsants which did not affect her daily life. Four and one-half years postoperatively she conceived, and had a healthy boy weighing 2,294 g at the 39th week of gestation in June 1985. Both mother and baby have been doing well for 7 postpartum years. PMID- 8489465 TI - A case report: cervical pregnancy with placenta percreta an ultrasonic assisted diagnosis. AB - A rare cervical pregnancy is reported, discussing the difficulty differentiating this condition from the cervical phase of an incomplete abortion. Placenta percreta further complicates this case. Ultrasound will give a firm diagnosis of cervical pregnancy and associated placenta percreta. Conservative and radical surgical care determined by vital signs are discussed. PMID- 8489466 TI - Sonographic prenatal diagnosis of congenital heart defects in thoraco omphalopagus. AB - Thoraco-omphalopagus is the most common variety of conjoined twins. About 90% of the conjoined thoraco-omphalopagus twins have a common pericardium, and 75% have conjoined hearts. Options for the treatment of thoraco-omphalopagus are largely dependent on the anatomy of the cardiovascular system. The extent of the conjunction of the heart and the severity of the associated cardiac defects primarily determine the feasibility of successful separation of the infants. Two dimensional echocardiography and color Doppler examination has become the method used to investigate cardiovascular system of conjoined twins with a high degree of confidence. A case of thoraco-omphalopagus conjoined twins prenatally determined of the extent of cardiac conjunction and diagnosis of associated defects by these methods is presented. PMID- 8489467 TI - Lupus anticoagulant (LAC) and its relation to pregnancy outcome: a report of five cases. AB - We examined the relation between the spontaneous remission and prednisolone induced suppression of lupus anticoagulant (LAC) or anticardiolipin antibody (ACA) and pregnancy outcome in 5 LAC-positive women. Two women showed a spontaneous remission of LAC and ACA during the observation period. One of these 2 women became pregnant and delivered healthy twin infants at 36 weeks of pregnancy without any therapy. The other woman became LAC positive again after 1 year of remission, and experienced 2 more fetal losses. Two of the remaining LAC positive women received prednisolone and aspirin. Only 1 woman, whose ACA was suppressed by medication, delivered a healthy newborn. The pregnancy of the other woman, whose LAC and ACA remained positive in spite of medication, terminated in an IUFD. These results suggest that the administration of prednisolone and aspirin is the first choice of therapy for LAC-positive women, and that encouraging such women to become pregnant while LAC is negative might be an alternative therapy. PMID- 8489468 TI - A case report on surgically managed elephantoid vulva due to donovanosis. PMID- 8489469 TI - Pregnancy in association with mitral valve prolapse. AB - Mitral valve prolapse (MVP) is considered to be the most common valvular heart lesion in adult females of reproductive age. Our report reviews the obstetrical performance and outcome of 34 pregnancies in 15 women with MVP. In 12 (80%) patients cardiac lesion was suspected due to enigmatic dyspnoea and palpitation during antenatal period. Four mothers required propranolol for cardiac arrhythmias. However, all of them tolerated pregnancy and labour well. Four pregnancies (11.8%) ended in spontaneous abortion and 1 mother had intrauterine fetal death due to severe pregnancy-induced hypertension. There were 25 (73.5%) term and 3 (8.8%) preterm neonates without congenital abnormality. One preterm neonate had tracheo-oesophageal fistula and died 6 hours after corrective surgery. The mean birth weight of 2.8 kg was appropriate for mean gestation of 38.5 weeks when compared to the Institute's reference neonatal weight curve. Infective endocarditis prophylaxis was recommended in cases having mitral regurgitation and complicated delivery. Awareness of this common cardiac lesion, thorough cardiovascular examination during pregnancy, early detection and treatment of cardiac arrhythmias if any, are the essential steps to prevent rare but dreaded maternal complications. PMID- 8489470 TI - Clinical observation of personality characteristics of perimenopausal women with undefined complaints. AB - Personality tests, including the Self-Rating Questionnaire for Depression (SRQ D), the Minnesota Multiphasic Personality Inventory Alexithymia Scale (MMPI-AS), and the Egogram Check List (ECL) were completed by 202 perimenopausal women with undefined complaints. Patients diagnosed as having mental disorders showed SRQ-D scores of over 16 points. Patients diagnosed as having mental disorders showed MMPI-AS scores of over 13 points, which can be estimated as alexithymia. Patients experiencing climacteric disorders and the ovarian deficiency syndrome showed slightly higher MMPI-AS scores than healthy middle-aged women. The average ECL scores of patients diagnosed as having mental disorders tended to show an N-shape pattern. The findings suggest that personality tests would be helpful for screening perimenopausal women with mental disorders who are seen at outpatient gynecology clinics. PMID- 8489471 TI - Predictive value of 1 hour 50 g oral glucose load screening test for gestational diabetes mellitus compared to 3 hour oral glucose tolerance test in high risk pregnant women. AB - A prospective study for detecting gestational diabetes mellitus was undertaken to evaluate the use of one hour plasma glucose level after 50 g glucose loading test (1-hr GLT) as compared to the traditional 3-hours 100 g oral glucose tolerance test (3-hr OGTT) in 396 high risk cases. Each patient, had 1-hr GLT and 3-hr OGTT performed in a separate week. Forty-two cases (10.6%) who had abnormal 3-hr OGTT were classified as gestational diabetes (GDM). One hundred and sixty cases (40.4%) had an abnormal 1-hr GLT (plasma glucose level > or = 140 mg/dl). Thirty six of these 160 cases (22.5%) had an abnormal 3-hr OGTT. In 236 women (59.6%) that had normal 1-hr GLT (plasma glucose level < 140 mg/dl) only 6 cases (2.5%) had an abnormal 3-hr OGTT. If 1-hr plasma glucose level > or = 150 mg/dl was used as the cutoff point, 110 cases (27.8%) were found to have abnormal 1-hr GLT, and 35 of these 110 cases (31.8%) had an abnormal 3-hr OGTT. Seven of 286 women (2.4%) that had normal 1-hr GLT (plasma glucose level < 150 mg/dl) had an abnormal 3-hr OGTT. The sensitivity and specificity of the 1-hr GLT when abnormal 3-hr OGTT was used as gold standard for detecting GDM were 85.7% and 65% respectively (BS > or = 140 mg/dl). Whereas the sensitivity and specificity were 83.3% and 78.8% respectively when plasma glucose level > 150 mg/dl was used as the cut point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489472 TI - Internal iliac artery ligation in obstetrics and gynecology. Ten years experience. AB - Twenty-two cases of bilateral internal iliac artery ligation done in the Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India over a period of 10 years (1981-1990) were studied. Various indications and complications were analysed. Internal iliac artery ligation is a life-saving procedure in pelvic hemorrhage. Complications are infrequents. PMID- 8489473 TI - Return of fertility after the removal of intrauterine devices: a comparison of inert and copper bearing devices. AB - The use of intrauterine device (IUD) has been suspected to be linked to involuntary infertility due to increased risk of pelvic inflammatory diseases. Nevertheless, it remains unclear whether the overall risk of infertility after discontinuing use of IUD increases with the duration of IUD use. Thus, the present study was designed to evaluate the return of fertility after discontinuing use of copper containing IUDs compared to inert IUD and to determine a possible relationship between the length of IUD use and return of fertility. Ninety women with Lippes Loop type D (LL), 88 women with Copper-T200 (TCu-200) and 83 women with Multiload Copper-250 (MLCu-250) were included in the analysis. The life table analysis and log rank-test showed that TCu-200 and MLCu 250 acceptors had a more rapid return of fertility compared to LL acceptors, although there was no significant difference in the return of fertility between TCu-200 and MLCu-250 acceptors. Compared to LL acceptors, the net cumulative probability of pregnancy after discontinuing use of IUD was 3 times higher in copper containing IUD acceptors in the first 3 months and somewhat higher in the first 4 to 11 months after removal of IUD. The length of use in copper containing IUDs (TCu-200 and MLCu-250) acceptors did not influence the return of fertility, whereas the return of fertility after removal of inert IUD (LL) was significantly higher in case of the use for shorter than 48 months compared to the use for longer than 48 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489474 TI - The impact of autologous bone marrow transplantation on hematopoietic recovery after high-dose cyclophosphamide, doxorubicin and cisplatin chemotherapy for patients with gynecological malignancies. AB - Twenty-six patients with gynecological malignancies (21 ovarian and 5 uterine malignant tumors) who were treated 42 times with high-dose cyclophosphamide, doxorubicin and cisplatin (CAP) chemotherapy with autologous bone marrow transplantation (ABMT) were assessed for the impact of predictive parameters on hematopoietic recovery. An inverse correlation was observed between the number of infused nucleated marrow cells (NMC)/kg or colony-forming units of granulocyte macrophage (CFU-GM)/kg and the leukopenic duration < 1 x 10(3)/microliters; the correlation coefficients were r = -0.54 and -0.49, respectively (p < 0.001). The recovery time of platelet count to achieve more than 5 x 10(4)/microliters without transfusion was inversely correlated with CFU-GM/kg (r = -0.33, p < 0.05) but not with NMC/kg. Neither the episodes of fever nor the number of chemotherapy courses performed on the patients influenced the hematopoietic recovery. The numbers of infused CFU-GM and NMC were useful parameters of leukopoietic recovery after ABMT and high-dose CAP chemotherapy. PMID- 8489475 TI - Y chromosome analysis and laparoscopic surgery in XY pure gonadal dysgenesis: a case report and a review of literature. AB - DNA analysis and laparoscopic surgery were performed on a patient with 46, XY pure gonadal dysgenesis. Southern-blot and polymerase chain-reaction analyses revealed that she had no apparent deletion of the Y chromosome, including the SRY gene (sex-determining region Y), suggesting that the patient might have some other abnormality. Since the risk of gonadal neoplasia in XY gonadal dysplasia is high, operative laparoscopy was performed to ensure that there was no malignancy in the patient. Laparoscopic surgery is recommended because of the amount of the surgery and the rapid postoperative recovery of the patient. PMID- 8489476 TI - The masked threshold to noise ratio in brainstem electric response audiometry: assessment of the conductive loss component by bone-conducted masking. AB - The aim of this study was to assess the conductive loss component (CLC) by brainstem electric response audiometry. A bone-conducted noise was used to mask out the response to a conventional air-conducted click stimulus. The difference between the levels of the click and the noise is defined as the masked threshold to noise ratio (MTNR). This MTNR was determined for 21 normal ears (MTNR = -13 +/ 5 dB). The increase in MTNR compared to this normative value is a measure of the CLC. For 10 ears with an artificially induced purely conductive loss, the increase in MTNR is in good agreement with the results of conventional pure-tone and brainstem electric response audiometry. PMID- 8489477 TI - Prevalence of tympanogram asymmetries and fluctuations in otitis media with effusion: implications for binaural hearing. AB - It has been suggested that asymmetric or fluctuating hearing in otitis media with effusion (OME) could lead to abnormal binaural hearing. In a cohort of children with tympanogram data obtained at 3-monthly intervals from 2 to 4 years, 6.4% had asymmetric or unilateral B tympanograms on more than half the test occasions, or had 5 or more fluctuations between symmetric and asymmetric tympanograms. Hence there are sufficient cases for studies of sequelae or treatment in unilateral and fluctuating OME. Few of these cases would have received medical attention under a bilateral referral criterion. PMID- 8489478 TI - Relative effective frequency response of bone versus air conduction stimulation examined via masking. AB - An adaptation of the sensorineural acuity level procedure was employed to obtain thresholds under bone- (BC) vs. air-conducted (AC) white noise masking. For the BC masking condition, a Radioear B71 was placed on one mastoid. An Etymotic ER3 with a foam tip placed in the ear on the same side was used to deliver the pure tone probe stimulus. This transducer was chosen to approximate the Telephonics TDH-39 earphone response characteristic while reducing occlusion effect. For the AC masking condition, the masker and probe were mixed electrically and delivered to the earphone. Masked threshold data, transformed into frequency response curves, demonstrated greater variance of BC vs. AC response across frequency but less high-frequency roll-off than expected from coupler measurements obtained using an artificial mastoid and 6-cm3 cavity, respectively. PMID- 8489479 TI - Spectral composition of infant auditory brainstem responses: implications for filtering. AB - Auditory brainstem responses (ABRs) were recorded from 20 normal neonates and 10 normal-hearing adults. The spectral compositions of ABRs from both groups were compared. Results indicated that significant amounts of low-frequency information are concentrated below 150 Hz in both the neonate and the adult ABRs although the neonate ABR has a slightly greater percentage of low-frequency information than that of the adults. This has implications for filtering during ABR recording. A low high-pass setting which preserves more of the low-frequency information will allow enhanced detectability of wave V in neonate ABRs recorded at low stimulus intensities. Furthermore, our experience indicates that the use of a 30- to 3,000 Hz bandpass is feasible in the neonatal intensive care unit as well as in the regular newborn nursery. Therefore the use of a 30- to 3,000-Hz bandpass is recommended for neonate ABR recordings. PMID- 8489480 TI - Influence of age on noise-induced permanent threshold shifts in CBA/Ca and C57BL/6J mice. AB - Two inbred strains of mice, CBA/Ca (showing a moderate hearing loss with onset late in life) and C57BL/6J (undergoing spontaneous auditory degeneration with onset during young adulthood), were exposed to a broad-band noise of 120 dB SPL (2-7 kHz) for 5 min at 1,2,3,6 or 12 (only for CBA) months of age. Permanent threshold shifts (PTS) were determined by recording auditory brainstem response (ABR) 1 month after exposure. C57 mice were more severely affected by acoustic trauma than age-matched CBA mice. With increasing age, susceptibility to PTS decreased in CBA mice but remained constant in C57 mice. Results indicate that the auditory system of CBA mice undergoes a progressive resistance to noise damage, whereas the persistent high susceptibility to acoustic trauma in C57 mice may be related to their genetic predisposition to rapid auditory degeneration. PMID- 8489481 TI - Comparison between self-hypnosis, masking and attentiveness for alleviation of chronic tinnitus. AB - The efficacy of self-hypnosis (SH), masking (MA) and attentiveness to the patient's complaints (AT) in the alleviation of tinnitus was evaluated. Forty five male patients close in age with chronic tinnitus related to acoustic trauma were assigned to three matched subgroups: SH, AT or MA. The therapeutic stimuli in the SH and MA sessions, recorded on audio cassettes, were given to the patients for use when needed. SH significantly reduced the tinnitus severity; AT partially relieved the tinnitus; MA did not have any significant effect. PMID- 8489482 TI - Pharmacology and molecular biology of adrenergic receptors. AB - The recent cloning of multiple adrenergic receptors has moved our understanding of these receptors from a conceptual one (Alquist, 1948) to one based on well defined unique cellular proteins. The biochemical and pharmacological properties of these receptors can now be studied in detail by expression of a single subtype in cells normally devoid of adrenergic receptors. By site-directed mutagenesis, the relationship between the structures of these receptors and their function is now being elucidated for each adrenergic receptor subtype. These functions include the binding of catecholamines and other ligands, G protein coupling and functional regulation. PMID- 8489483 TI - Plasma catecholamines--analytical challenges and physiological limitations. AB - Catecholamines in plasma may be measured to assess sympathoadrenal activity. Numerous assay methodologies have been published, illustrating the fact that there are many analytical problems. Different methodologies are discussed briefly. A plea for better validation, especially with regard to specificity (which should not be confused with sensitivity or reproducibility), is made. Plasma NA is a frequently used marker for sympathetic nerve activity in humans, but the data obtained are often misinterpreted due to lack of appreciation of the physiological determinants of the NA concentration measured. NA overflow from an organ gives a good reflection of nerve activity in that organ. However, sympathetic nerve activity is highly differentiated, particularly during stress, and conventional plasma NA levels (usually forearm venous samples) cannot be taken as an indication of 'sympathetic tone' in the whole individual. NA is rapidly removed from plasma, resulting in meaningless net veno-arterial concentration differences over organs unless its removal from arterial plasma is taken into account. In the forearm, for example, 40-50% of catecholamines are removed during one passage; about half of the NA in a venous sample is derived from the arm and half from the rest of the body. Therefore, conventional venous sampling overemphasizes local (mainly skeletal muscle) nerve activity. Whole-body sympathetic nerve activity may be monitored in arterial or mixed venous (i.e. pulmonary arterial) samples, which reflect NA overflow from all organs in the body. NA levels are determined both by overflow to plasma and clearance from plasma. NA turnover studies with 3H-NA infusions may be needed to assess clearance, but the simpler concentration measurements usually yield adequate information if the sampling site is relevant. NA overflow from an organ can be assessed (using 3H-NA or ADR as a marker for NA extraction in the organ) and provides valuable information on local sympathetic activity. Mental stress elicits marked circulatory responses, with mainly cardiorenal sympathetic activation and minor elevations of conventional venous plasma NA levels, thus illustrating the differentiated firing pattern of the sympathetic nerves. Circulating ADR is less important than neurogenic mechanisms in the responses to stress. Concentration-effect studies for infused catecholamines may be used for receptor sensitivity studies in vivo, but reflexogenic contributions to responses need to be determined. However, prejunctional mechanisms cannot be assessed without knowledge of the nerve activity present; for example, ADR infusion leads to increased nerve activity. When correctly sampled, measured and interpreted, plasma catecholamines can yield very valuable information on sympathoadrenal activity. PMID- 8489484 TI - Metabolic actions of catecholamines in man. PMID- 8489485 TI - Catecholamines and essential hypertension. AB - Given the ubiquitous distribution of catecholamines in mammals, and their importance in a range of physiological processes pivotal to blood pressure regulation, the subject of catecholamines and essential hypertension has a broader context than simply consideration of sympathetic nervous system and adrenal medullary dysfunction. These further matters are the likely involvement in hypertension pathogenesis of the CNS catecholaminergic neurones influencing peripheral sympathetic outflow, the possible pathogenetic significance of adrenaline released as a cotransmitter in sympathetic nerves, and the natriuretic renal tubular dopamine mechanisms for regulating body sodium balance which appear to be impaired in patients with essential hypertension. The central consideration, however, remains the important issue of the causes and consequences of the now well-documented sympathetic nervous overactivity which characterizes the early developmental phases of essential hypertension. PMID- 8489486 TI - Sympathetic dysfunction in heart failure. AB - CHF is a common, complex and life-threatening clinical syndrome. It is widely accepted that enhanced peripheral vascular tone plays a major role in the pathophysiology of CHF. Increased activity of the sympathetic nervous system is one of the most important factors responsible for the increased afterload in CHF. This increase in sympathetic activity occurs early in the course of development of CHF. Efferent sympathetic activity is distributed in a non-uniform way in CHF, with significant increases to the heart and kidney but normal activity to some other organs such as the lung. Increased renal sympathetic activity contributes significantly to altered neural haemodynamics, sodium and water retention, and modulation of the actions of other vasoactive hormones. The regional alteration in sympathetic activity may be largely responsible for the changes in resting regional blood flow to different organs in CHF and the maldistribution of blood flow that occurs during the stress of exercise. Disordered function of cardiovascular reflexes is observed in CHF and may contribute to disordered sympathetic function. In CHF there are significant interactions between the sympathetic nervous system and other humoral systems such as the renin angiotensin system, AVP, ANP, endothelin and renal DA. The various drugs used in the treatment of CHF have different effects on sympathetic activity: digitalis and ACE inhibitors tend to suppress activity while diuretics may have the opposite effect. Following cardiac transplantation, there is a prompt return of sympathetic function towards normal, although the heart may remain significantly denervated for a long time, with gradual reinnervation. Cyclosporin therapy tends to increase sympathetic activity and this may contribute to post-transplant hypertension. PMID- 8489487 TI - Sympathetic nervous system disorders in man. AB - The sympathetic nervous system innervates most organs in the body and controls their function. A variety of disease processes, surgery or drugs can result in disordered sympathetic nerve function, which can be either localized or more generalized. Malfunction can result in either sympathetic underactivity (causing postural hypotension, impotence or anhidrosis) or overactivity (causing paroxysmal hypertension or hyperhidrosis). The investigation of sympathetic disorders depends upon the system and organs involved and should include, where relevant, investigation of the possible aetiological processes. The clinical features and management of some of the major disorders affecting the sympathetic nervous system, including the recently described syndrome of DBH deficiency, are described. PMID- 8489488 TI - Imaging of catecholamine-secreting tumours: uses of MIBG in diagnosis and treatment. AB - MIBG radiolabelled with 131I or 123I is a radiopharmaceutical which is concentrated in neuroendocrine tumours, particularly phaeochromocytomas and neuroblastomas. This permits non-invasive whole-body scintigraphic screening for benign and malignant, familial and sporadic, intra-adrenal and extra-adrenal phaeochromocytomas and primary and metastatic neuroblastomas, with high sensitivity (85-90%) and specificity (> 95%). MIBG is also concentrated in presynaptic terminals of adrenergic, autonomically innervated organs such as the heart, and may be used as a non-invasive in vivo probe to study this system. Large doses of 131I-MIBG and 125I-MIBG have been used experimentally to selectively deliver therapeutic doses of radiotherapy to malignant phaeochromocytomas and refractory advanced neuroblastomas. PMID- 8489489 TI - Phaeochromocytoma and paraganglioma. AB - Use of current analytical techniques should lead to the successful diagnosis of most catecholamine-secreting tumours, and the experience and confidence which has evolved with the use of HPLC-ECD for plasma and urinary catecholamine estimation, as well as their greater diagnostic sensitivity and specificity, should soon render the older urinary assays based on catecholamine metabolites obsolete. Until then urinary metanephrine estimation will remain the diagnostic metabolite of choice. The diagnosis of small lesions and early recurrences will, however, continue to pose a great analytical challenge, and may call for the use of suppressive tests such as the pentolinium suppression test, venous catheterization, and MIBG scanning. The flow chart used for phaeochromocytoma diagnosis in our department is illustrated in Figure 12; and provides a strategy for the effective diagnosis of all but the most difficult lesions. PMID- 8489490 TI - [Homeopathy in veterinary medicine and its pharmacologic/toxicologic and drug regulatory evaluation]. AB - This review gives a summary of the definitions, delimitations and principles of homeopathy and its potential mechanisms of action, which is followed by an overview and critical evaluation of the most important homeopathic drugs registered for treatment of animals. It is shown that several of the marketed homeopathic drugs for treatment of animals violate current drug laws and represent a risk for both the animals and the consumer of food produced from animals. Based on these potential risks of homeopathic treatments, new EC regulations were recently published, which will markedly affect (and hopefully improve) the current situation of veterinary homeopathic drugs. PMID- 8489491 TI - [Causes of kyphotic and lordotic curvature of the spine with cuneiform vertebral deformation in swine]. AB - Clinical, radiographic and pathological findings demonstrate that kyphosis in 11 weaned pigs with formation of wedge shaped vertebrae can be caused by congenital malformation, traumatic lesion (fracture), inflammation (osteomyelitis), metabolic bone disease or abnormal body posture following chronically painful diseases. Lordosis in 2 weaned pigs with cuneiform deformations of the dorsal part of vertebrae was also caused by developmental malformations or abnormal body posture (polyarthritis). No evidence of heredity in the group of congenital vertebral malformations was found. PMID- 8489493 TI - Is complex II involved in the inhibition of mitochondrial respiration by N-methyl 4-phenylpyridinium cation (MMP+) and N-methyl-beta-carbolines? AB - It has been reported that N-methyl-beta-carbolinium analogues of the neurotoxic N methyl-4-phenylpyridinium cation (MPP+) inhibit NADH-linked mitochondrial oxidations, as well as mitochondrial respiration on succinate nearly to the same extent [Fields, Albores, Neafsey and Collins (1992) Arch. Biochem. Biophys. 294, 539-544]. Those authors further claimed that MPP+ itself also blocks respiration through succinate dehydrogenase, in addition to its well-known effect on NADH dehydrogenase (Complex I), and concluded that both effects may contribute to the development of Parkinsonian symptoms. Since N-methyl-beta-carboliniums are thought to be endogenous metabolites, these findings, if verified, would have important implications on the etiology of idiopathic Parkinsonism. We have re examined these observations, using mitochondria after full activation of succinate dehydrogenase, as well as submitochondrial particles, in which complexities due to membrane transport are not present. We report the following observations. (1) N-Methyl-beta-carboliniums inhibit mitochondrial respiration on NAD(+)-linked substrates in a time-dependent manner, and the inhibition is potentiated by the presence of tetraphenylboron anion (TPB-), as expected for positively charged compounds. (2) Unlike MPP+ itself, however, these compounds are uncouplers at higher concentrations, so that the effects seen in State 3 cannot be assigned exclusively to inhibition of NADH oxidation. (3) The effects on succinate oxidation in mitochondria, in which the full activity of the enzyme is expressed, are 1-1.5 orders of magnitude lower than on respiration via Complex I and are thus unlikely to contribute significantly to the neurotoxicity. (4) The effect of MPP+ on mitochondrial respiration via succinate dehydrogenase is trivial, in accord with previous reports from several laboratories, but contradicting the findings of Fields et al. (cited above). (5) In submitochondrial particles the inhibition of NADH oxidation (via the complete respiratory chain) has been confirmed, but it differs markedly from the action of MPP+ in two respects. First, the enhancement by TPB- is very small; secondly, the inhibition of NADH oxidation measured using ubiquinone (Q) analogues is far lower, suggesting that Complex I is not the only target. (6) In submitochondrial particles the inhibition of succinate oxidation by either O2 or Q analogues is incomplete, trivial or absent. (7) We thus conclude that we find no basis for assigning any potential biological effect of N-methyl-beta-carboliniums to the blockade of succinate oxidation. PMID- 8489492 TI - Molecular genetics of actin function. PMID- 8489494 TI - The bioactive phospholipid lysophosphatidic acid is released from activated platelets. AB - Lysophosphatidic acid (LPA) is a water-soluble phospholipid with hormone-like and growth-factor-like activities. LPA activates a putative G-protein-coupled receptor in responsive cells, but the natural source of exogenous LPA is unknown. Here we show that LPA is present in mammalian serum in an active form (bound to albumin) at concentrations of 1-5 microM, but is not detectable in platelet-poor plasma, suggesting that LPA is produced during blood clotting. We find that thrombin activation of platelets prelabelled with [32P]Pi results in the rapid release of newly formed [32P]LPA into the extracellular environment. We conclude that LPA is a novel platelet-derived lipid mediator that may play a role in inflammatory and proliferative responses to injury. PMID- 8489495 TI - Absence of phosphocreatine resynthesis in human calf muscle during ischaemic recovery. AB - Changes in the metabolites phosphocreatine (PCr), Pi and ATP were quantified by 31P n.m.r. spectroscopy in the human calf muscle during isometric contraction and recovery under ischaemic conditions. Time resolution of the measurements was 10 s. During a 30-60 s ischaemic isometric contraction, PCr decreased linearly at a rate of 1.17%/s (relative to the resting value) at a contraction strength equivalent to 70% of the maximal voluntary contraction (MVC) and at a rate of 2.43%/s at 90% MVC. There was a corresponding increase in Pi but the concentration of ATP did not change. pH decreased linearly during contraction by 4.22 and 8.23 milli-pH units/s at 70 and 90% MVC respectively. During a subsequent 5 min interval of ischaemic recovery, PCr, Pi, ATP, phosphomonoesters and calculated free ADP, free AMP and pH retained the value they had attained by the end of contraction with no significant recovery. Thus it is concluded that anaerobic glycolysis and glycogenolysis is halted momentarily on termination of contraction and that PCr is not resynthesized during ischaemic recovery. This paradoxical arrest of glycolytic flow in spite of the very significantly elevated concentration of potent activators such as Pi and free AMP clearly indicates that parameters other than PCr, ATP, Pi, calculated pH, free ADP and free AMP regulate glycolysis and glycogenolysis of human skeletal muscle very efficiently under ischaemic conditions. PMID- 8489496 TI - Purification and reactivation of recombinant Synechococcus phytoene desaturase from an overexpressing strain of Escherichia coli. AB - The Synechococcus phytoene desaturase has been isolated from an overexpressing strain of Escherichia coli. The plasma pPDSde135 mediated the overexpression of the full-length polypeptide directly. The recombinant protein comprised 5% of the total cellular protein and was found predominantly in the inclusion body fraction. Urea was used to solubilize the recombinant protein from the inclusion fraction and the protein was subsequently purified to homogeneity on a DEAE cellulose column. The purification scheme yielded 4.0 mg of homogeneous desaturase protein after a 20-fold purification, recovering 40% of the original protein from a 100 ml suspension culture of E. coli. The recombinant desaturase had an apparent molecular mass of 53 kDa on SDS/PAGE and crossreacted with an antiserum raised against the expressed protein. Desaturase activity was restored upon the removal of urea. The enzyme catalysed the conversion of phytoene to zeta carotene via phytofluene. These products of the desaturase reaction existed predominantly in a cis configuration. Lipid replenishment enhanced activity. NAD+ and NADP+ were observed to be involved, whilst FAD was an ineffective electron acceptor. PMID- 8489497 TI - Retinol esterification in bovine retinal pigment epithelium: reversibility of lecithin:retinol acyltransferase. AB - Esterification of all-trans-retinol is a key reaction of the vertebrate visual cycle, since it produces an insoluble, relatively non-toxic, form of the vitamin for storage and supplies substrate for the isomerization reaction. CoA-dependent and -independent pathways have been described for retinol esterification in retinal pigment epithelium (RPE). The CoA-independent reaction, catalysed by lecithin:retinol acyltransferase (LRAT) was examined in more detail in this study. Addition of retinol to RPE microsomes results in a burst of retinyl ester synthesis, followed by a rapid apparent cessation of the reaction. However, [3H]retinol, added when retinyl ester synthesis has apparently ceased, is rapidly incorporated into retinyl ester without a net increase in the amount of ester. The specific radioactivities of [3H]retinol and [3H]retinyl ester reach the same value. [14C]Palmitate from palmitoyl-CoA is incorporated into preexisting retinyl ester in the absence of net ester synthesis, too. These exchange reactions suggest that the reaction has reached equilibrium at the plateau of the progress curve and that only the accumulation of retinyl ester, and not its synthesis, has stopped during this phase of the reaction. Studies with geometrical isomers of retinol revealed that the rate of exchange of all-trans-retinol with all-trans retinyl esters was about 6 times more rapid than exchange of 11-cis-retinol with 11-cis-retinyl ester. This is the first demonstration of the reversibility of LRAT and the first example of stereospecificity of retinyl ester synthesis in the visual system. Reversal of the LRAT reaction could contribute to the mobilization of 11-cis-retinol from 11-cis-retinyl ester pools. PMID- 8489498 TI - Energy transduction by nitrogenase: binding of MgADP to the MoFe protein is dependent on the oxidation state of the iron-sulphur 'P' clusters. AB - Hydrolysis of MgATP to MgADP is essential for nitrogenase action. There is good evidence for binding of both nucleotides to the Fe protein of nitrogenase, but data indicating their binding to the MoFe protein have been controversial [see Miller and Eady (1989) Biochem. J. 263, 725-729]. The binding of MgADP to the MoFe protein of nitrogenase of Klebsiella pneumoniae was investigated by non equilibrium gel-filtration column methods. No binding of MgADP to the dithionite reduced protein could be detected. Treatment of the MoFe protein with phenosafranine [midpoint potential (Em) -270 mV] did not affect the activity, and oxidized the 'P' clusters but not the iron-molybdenum cofactor (FeMoco) centres. This oxidized species bound 3.9 mol of MgADP with a binding pattern characteristic of low rates of ligand dissociation. These observations suggest that the variability in published data on nucleotide binding to the MoFe protein is related to poor control of the protein oxidation level. Our data, coupled with the observation that 'P' clusters become oxidized during reduction of N2 [Lowe, Fisher and Thorneley (1993) Biochem. J., in the press], led us to propose that the ADP binding sites are transiently filled during enzyme turnover by hydrolysis of ATP originally bound to the Fe protein, and that hydrolysis occurs on a bridging site on the MoFe-Fe-protein complex. PMID- 8489499 TI - Evidence for N-linked glycosylation in Toxoplasma gondii. AB - In this paper we report experiments demonstrating the presence of N-linked oligosaccharide structures in Toxoplasma gondii tachyzoites, providing the first direct biochemical evidence that this sporozoan parasite is capable of synthesizing N-linked glycans. The tachyzoite surface glycoprotein gp23 was metabolically labelled with [3H]glucosamine and [3H]mannose. Gel-filtration chromatography on Bio-Gel P4 columns produced four radiolabelled N-linked glycopeptides which were sensitive to peptidase-N-glycanase F, but resistant to endoglycosidases H and F. Using chemical analysis and exoglycosidase digestions followed by Dionex-high-pH anion-exchange chromatography and size fractionation on Bio-Gel P4 we show that gp23 has N-linked glycans in the hybrid- or complex type structure composed of N-acetylgalactosamine, N-acetylglucosamine and mannose and devoid of sialic acid and fucose residues. In addition, the sensitivity of glycopeptides from glycoprotein extracts to endoglycosidases H and F revealed the in vivo synthesis of oligomannose-type structures by T. gondii tachyzoites. We have extended these findings by demonstrating the ability of T. gondii microsomes to synthesize in vitro a glucosylated lipid-bound high-mannose structure (Glc3Man9GlcNAc2) that is assumed to be identical with the common precursor for N glycosylation in eukaryotes. PMID- 8489500 TI - Intracellular maturation of the gamma-carboxyglutamic acid (Gla) region in prothrombin coincides with release of the propeptide. AB - Vitamin K-dependent coagulation factors undergo several post-translational modifications before the proteins are secreted into the blood as functional zymogens of the coagulation system. The modifications include Asn-linked glycosylation, Asn/Asp hydroxylation, removal of a signal peptide for translocation of the polypeptide into the endoplasmic reticulum and removal of a propeptide which, when attached to the intracellular coagulation factor precursor, directs the protein for vitamin K-dependent gamma-carboxylation. gamma Carboxylation of targeted Glu residues results in formation of Ca(2+)-binding gamma-carboxyglutamic acid (Gla) residues. Ca2+ binding by these residues induces a conformational change in the protein which is a necessary event for optimal activation or activity of the clotting factor in blood. In the present study we have monitored the intracellular prothrombin precursor in the secretory pathway of liver cells to determine the effect that the propeptide has on Ca(2+) dependent folding of the protein. The data provide evidence that the Ca(2+) induced conformational change required for activation of prothrombin coincides with release of the propeptide in the trans-Golgi apparatus of the liver cell and elucidates an important function for the endoproteinase furin in biosynthesis of vitamin K-dependent clotting factors. PMID- 8489501 TI - Biogenic-amine acetylation: an additional function of the N-acetyltransferase from Fasciola hepatica. AB - The previously described polyamine N-acetyltransferase from Fasciola hepatica has been observed to have an additional function, the acetylation of biogenic amines. The activities for biogenic amines, diamines and polyamines were in a constant ratio throughout the purification process. Biogenic amines found to be substrates for the enzyme included tyramine, tryptamine, beta-phenylethylamine and histamine, with Km values of 0.12 mM, 0.26 mM, 0.30 mM and 0.76 mM respectively. Octopamine, 5-hydroxytryptamine and alpha-phenylethylamine were also acceptable as substrates, though to a lesser degree. The optimum pH for biogenic-amine acetylation was 7.5, and CoA was inhibitory to the process, with a Ki of 5.5 microM. N-Acetylation appears to play a major role in the amine metabolism of this trematode. We presume that acetylation represents the process by which the parasite inactivates excess amines. PMID- 8489502 TI - Control of the effective P/O ratio of oxidative phosphorylation in liver mitochondria and hepatocytes. AB - The control exerted by substrate oxidation reactions, by ATP turnover and by the proton leak over the oxygen consumption rate, the phosphorylation rate, the proton leak rate and the protonmotive force (delta p) in isolated rat liver mitochondria under a range of conditions between non-phosphorylating (State 4) and maximum phosphorylation (State 3) was investigated by using the top-down approach of metabolic control analysis. The experiments were carried out with saturating concentrations of the substrates succinate, glutamate with malate, or pyruvate with malate. The distribution of control was very similar with each of the three substrates. The effective P/O ratio (i.e. not corrected for leak reactions) was also measured; it varied from zero in State 4 to 80-90% of the maximum theoretical P/O ratio in State 3. Under most conditions control over the effective P/O ratio was shared between proton leak (which had negative control) and the phosphorylating subsystem (which had roughly equal positive control); near State 4, substrate oxidation reactions also acquired some control over this ratio. In resting hepatocytes the effective P/O ratio was only 50% of its maximum theoretical value, corresponding to an effective P/O ratio of only 1.3 for complete oxidation of glucose. The effective P/O ratio for intracellular mitochondrial oxygen consumption was 64% of the maximum value. The control coefficient of the mitochondrial proton leak over the effective P/O ratio in cells was -0.34; the control coefficient of phosphorylation reactions over this ratio was 0.31 and the control coefficient of substrate oxidation reactions over the ratio was 0.03, showing how the coupling efficiency in cells can respond sensitively to agents that change the proton leak or the ATP demand, but not to those that change substrate oxidation. PMID- 8489503 TI - Endocytosis of ricin by rat liver cells in vivo and in vitro is mainly mediated by mannose receptors on sinusoidal endothelial cells. AB - Upon intravenous injection into rats, the plant toxin ricin was rapidly cleared from the circulation by the liver. Among the different liver cell populations, most of the injected ricin associated with the sinusoidal endothelial cells (EC), whereas the liver parenchymal cells (PC) and Kupffer cells (KC) yielded minor contributions to the total liver uptake in vivo. Co-injection of mannan strongly inhibited ricin uptake by the EC, showing that it was mediated by mannose receptors. On the other hand, co-injection of lactose, which inhibits the galactose-specific association of ricin with cells, enhanced ricin uptake by the EC. The carbohydrate-dependency of the EC contribution to the uptake of ricin in vivo was reflected in the carbohydrate-dependency of the uptake in vivo by whole liver. In vitro, the EC also endocytosed ricin more efficiently than did the PC or KC. Whereas uptake in vitro in the EC was mainly mannose-specific, uptake in the two other cell types was mainly galactose-specific. Western blotting showed that the mannose receptors of liver non-parenchymal cells are identical with the mannose receptor previously isolated from alveolar macrophages. The mannose receptors are expressed at a higher level in EC than in KC. Ligand blotting showed that, in the presence of lactose, the mannose receptor is the only protein in the EC that binds ricin, and the binding is mannose-specific and Ca(2+) dependent. PMID- 8489504 TI - Role of maltase in the utilization of sucrose by Candida albicans. AB - Two isoenzymes of maltase (EC 3.2.1.20) were purified to homogeneity from Candida albicans. Isoenzymes I and II were found to have apparent molecular masses of 63 and 66 kDa on SDS/PAGE with isoelectric points of 5.0 and 4.6 respectively. Both isoenzymes resembled each other in similar N-terminal sequence, specificity for the alpha(1-->4) glycosidic linkage and immune cross-reactivity on Western blots using a maltase II antigen-purified rabbit antibody. Maltase was induced by growth on sucrose whereas beta-fructofuranosidase activity could not be detected under similar conditions. Maltase I and II were shown to be unglycosylated enzymes by neutral sugar assay, and more than 90% of alpha-glucosidase activity was recoverable from spheroplasts. These data, in combination with other results from this laboratory [Geber, Williamson, Rex, Sweeney and Bennett (1992) J. Bacteriol. 174, 6992-6996] showing lack of a plausible leader sequence in genomic or mRNA transcripts, suggest an intracellular localization of the enzyme. To establish further the mechanism of sucrose assimilation by maltase, the existence of a sucrose-inducible H+/sucrose syn-transporter was demonstrated by (1) the kinetics of sucrose-induced [14C]sucrose uptake, (2) recovery of intact [14C]sucrose from ground cells by t.l.c. and (3) transport of 0.83 mol of H+/mol of [14C]sucrose. In total, the above is consistent with a mechanism whereby sucrose is transported into C. albicans to be hydrolysed by an intracellular maltase. PMID- 8489505 TI - Characterization of neutral endopeptidase 24.11 in dog glomeruli. AB - Neutral endopeptidase (NEP; also known as neprilysin and enkephalinase; EC 3.4.24.11) is a cell-surface metallopeptidase that is present in many mammalian tissues. It is particularly abundant on the brush-border membranes of the kidney proximal tubule. In this paper, the presence of NEP in purified glomeruli from dog kidney was assessed by measuring phosphoramidon- and thiorphan-sensitive [D Ala2,Leu5]enkephalin-degrading activity. Using this assay, the Km and kcat. of the glomerular enzyme were found to be identical to those of the tubular enzyme. By Western blotting the apparent M(r) of the glomerular enzyme was found to be 104,000, compared with 94,000 for the tubular enzyme. This might be due to a different glycosylation pattern, since endoglycosidase F treatment of NEP obtained from both tissues yielded deglycosylated enzymes with similar electrophoretic mobilities. The glomerular enzyme also appears to be membrane bound, since it was retained in the detergent-rich phase after phase separation with Triton X-114. Autoradiography experiments performed with RB104, a new highly selective and potent NEP inhibitor, showed that NEP was expressed in both glomeruli and proximal tubules. The presence in glomeruli of NEP and some other brush-border peptidases (dipeptidyl-dipeptidase IV, aminopeptidase N and angiotensin I-converting enzyme) suggests that cell-surface peptidases might play an important role as regulators of plasma-derived peptides in this part of the nephron. PMID- 8489506 TI - Cloning and sequence analysis of cDNAs encoding the alpha 1, alpha 2 and alpha 3 chains of mouse collagen VI. AB - cDNA clones encoding the alpha 1, alpha 2 and alpha 3 chains of mouse collagen VI have been isolated by screening cDNA libraries with the corresponding human probes. The composite cDNAs for the alpha 1, alpha 2, and alpha 3 chains are 2.5, 1.6 and 2.9 kb in size respectively. The alpha 1 and alpha 2 cDNAs encode the C terminal portions of the chains as well as the entire 3'-untranslated regions, while the alpha 3 cDNAs encode a central segment of 959 amino acids flanking the triple-helical domain. The deduced amino acid sequences share 86-88% identity with the human counterparts and 67-73% identity with the chicken equivalents. Alignment of the deduced amino acid sequences of mouse, human and chicken collagens reveal that the key features of the protein, including the cysteine residues, imperfections in the Gly-Xaa-Xaa regions, Arg-Gly-Asp sequences and potential N-glycosylation sites, are mostly conserved. PMID- 8489507 TI - Effect of temperature on bradykinin-induced arachidonate release and calcium mobilization in vascular endothelial cells. AB - The effect of decreased temperature on Ca(2+)-dependent arachidonic acid release was studied in vascular endothelial cells by investigating bradykinin (BK) stimulated Ca2+ mobilization, inositol phosphate formation and arachidonic acid release. At both 37 degrees C and 22 degrees C, BK efficiently increased cytosolic Ca2+ concn. ([Ca2+]i). At 22 degrees C, peak [Ca2+]i was higher and returned to basal levels more slowly. Although this response was preceded by rapid formation of Ins(1,4,5)P3, the activity of phospholipase C was significantly impaired at 22 degrees C. To determine if Ins(1,4,5)P3 effectively mobilized intracellular Ca2+, we used saponin-permeabilized cells. Ins(1,4,5)P3, mobilized sequestered Ca2+ to a similar degree at 37 degrees C and 22 degrees C, although Ca2+ release was prolonged at 22 degrees C. In intact cells, BK mobilized intracellular Ca2+ stores and activated Ca2+ entry. The rate of 45Ca2+ entry was approx. 2-fold slower at 22 degrees C, even though the peak and duration of the rise in [Ca2+]i were higher and sustained at the lower temperature. TG mobilized intracellular Ca2+, activated Ca2+ entry and elevated [Ca2+]i at both temperatures. As with BK, the peak [Ca2+]i reached after thapsigargin treatment was higher at 22 degrees C. This effect of lower temperature on [Ca2+]i was most probably due to decreased Ca2+ efflux after a decrease in activity of the Ca(2+)-ATPase on the plasma membrane. Both A23187 and BK were shown to stimulate phospholipase A2 and arachidonic acid release at 22 degrees C. In each case, the rate and extent of release were decreased compared with that at 37 degrees C. Among several effects, lowering the temperature decreases the activity of phospholipase C, Ca(2+)-ATPase(s), Ca(2+)-entry mechanisms and phospholipase A2. Together, these effects lead to a higher and more prolonged elevation of [Ca2+]i, but a decrease in arachidonate release in response to BK. PMID- 8489508 TI - Isoenzymes of protein kinase C in rat mammary tissue: changes in properties and relative amounts during pregnancy and lactation. AB - Protein kinase isoenzymes belonging to the protein kinase C (PK-C) family present in rat mammary tissue have been resolved from one another by chromatography on hydroxyapatite, and characterized. PK-C alpha is the predominant isoenzyme and is present at a constant level of activity throughout mammary-gland development and differentiation. In contrast, marked changes in the relative abundance of other mammary PK-C isoenzymes accompany the transition from pregnancy to lactation. The sensitivity of mammary PK-C alpha to Ca2+ is greater in tissue from pregnant than from lactating rats. This isoenzyme has other atypical properties consistent with its being more highly phosphorylated than PK-C alpha in rat brain and spleen. One of the protein kinase isoenzymes resolved from mammary tissue recognizes the peptide substrate used to assay AMP-activated kinase and may thus interfere in the determination of this activity. Another is fully active in the absence of Ca2+ and is more than 80% active in the absence of added lipid effectors. A 'housekeeping' role is proposed for PK-C alpha in mammary tissue, whereas the less abundant PK-C isoenzymes may be involved in mammary cell proliferation and differentiation. PMID- 8489509 TI - Effect of 5'-deoxy-5'-isobutylthioadenosine on formation and release of adenosine from neonatal and adult rat ventricular myocytes. AB - 1. Studies in rat polymorphonuclear leucocytes have suggested that 5'-deoxy-5' isobutylthioadenosine (IBTA), an inhibitor of the IMP-selective cytosolic 5' nucleotidase, may be used to test its role in adenosine formation in intact cells. We investigated adenosine formation in neonatal and adult rat cardiomyocytes. 2. 2-Deoxyglucose (30 mM) with oligomycin (2 micrograms/ml) induced a 90-100% fall in ATP concentration in 10 min in neonatal and 60 min in adult heart cells. Adenosine accumulation was substantially increased, accounting for 13% of the fall in ATP concentration in neonatal cells and 56% in adult cells. 3. Anti-(rat liver ecto-5'-nucleotidase) serum did not inhibit adenosine accumulation. Furthermore, dipyridamole (10 microM), a nucleoside-transport blocker, inhibited by 80% the appearance of the newly formed adenosine in the medium, showing that adenosine is produced intracellularly by both adult and neonatal-rat myocytes in response to inhibition of oxidative metabolism. 4. IBTA (3 mM) inhibited by 80% the appearance of adenosine in the medium, but did not inhibit total adenosine accumulation by neonatal-rat myocytes and only modestly inhibited total adenosine accumulation by adult myocytes. 5. IBTA, like dipyridamole, inhibited incorporation of extracellular adenosine (10 microM) into neonatal and adult ventricular myocyte nucleotides by 60-70%. Transport of IBTA (100 microM) into the cells did not appear to be inhibited by dipyridamole (30 microM). 6. We conclude that IBTA acted primarily to inhibit adenosine release from myocytes. The small effect on adenosine formation rates implies that the IMP selective cytosolic 5'-nucleotidase plays a minor role in this tissue. PMID- 8489510 TI - Alternative route for the biosynthesis of polyunsaturated fatty acids in K562 cells. AB - K562 human leukaemia cells lack a significant delta 6-desaturase activity. However, they synthesize long-chain polyunsaturated fatty acids (PUFA) from linoleic (C18:2(9,12)) and linolenic (C18:3(9,12,15)) acids, by reactions involving a C2 chain elongation followed by a delta 5-desaturation step and, to some extent, a further elongation. The main products formed were separated by argentation t.l.c. and identified by g.l.c. as the uncommon fatty acids C20:3(5,11,14) and C20:4(5,11,14,17) respectively. These acids were also produced when cells were supplemented with C20:2(11,14) or C20:3(11,14,17) respectively. The presence of a delta 5-desaturase was further confirmed by using its corresponding normal substrates, C20:3(8,11,14) and C20:4(8,11,14,17), which led to C20:4(5,8,11,14) and C20:5(5,8,11,14,17) respectively. On the other hand, a high delta 9-desaturase activity, but no significant delta 4-desaturase activity, were detected in K562 cells. These results indicate the existence of an alternative pathway, involving delta 5-desaturase, which is the only route for PUFA biosynthesis in K562 cells. This pathway may be relevant for the biosynthesis of PUFA in cells lacking delta 6-desaturase activity. PMID- 8489512 TI - Role of tryptophan-388 of GLUT1 glucose transporter in glucose-transport activity and photoaffinity-labelling with forskolin. AB - GLUT1 glucose-transporter cDNA was modified to substitute leucine for Trp-388 and transfected into Chinese hamster ovary cells using the expression vector termed pMTHneo. This tryptophan residue is conserved among most of the facilitative glucose-transporter isoforms and has been proposed to be the photolabelling site of forskolin, a competitive inhibitor of glucose transport. In addition, this residue is located on membrane-spanning helix 10 which is suggested to contain the dynamic segment of the transporter. The mutated glucose transporter was expressed and inserted into the plasma membrane in a fashion similar to the wild type. Unexpectedly, this mutation did not abolish photolabelling with forskolin. However, the mutation induced a marked decrease in 2-deoxyglucose uptake with a 4 fold decrease in turnover number and a 1.25-fold increase in Km compared with the wild-type GLUT1. A similar decrease in zero-trans influx activity was also observed for 3-O-methylglucose. In contrast, no apparent decrease was observed in zero trans efflux activity for 3-O-methylglucose. The mutation decreased the turnover number of the glucose transporter in equilibrium exchange influx for 3-O methylglucose by 33% without any change in Km. These results indicate that (1) Trp-388 is not the photolabelling site for forskolin, if we assume that the labelling occurs at a single site and (2) Trp-388 is more likely to be involved in interconversion between the inward-facing and outward-facing conformers of GLUT1 than binding of glucose, and thus, substitution of leucine for Trp-388 in this dynamic segment would decrease the rate of alternating conformation, which would preferentially affect the influx activity. PMID- 8489511 TI - Fragmentation of human polymorphonuclear-leucocyte collagenase. AB - Human polymorphonuclear-leucocyte collagenase (M(r) 64,000) shows autoproteolytic degradation to two major fragments of M(r) 40,000 and M(r) 27,000. N-terminal sequence data and investigation of the substrate specificity of the fragments demonstrate that the M(r)-40,000 fragment corresponds to the catalytic domain, whereas the M(r0-27,000 fragment shows no enzymic activity. The activity profile of the M(r)-40,000 fragment is comparable with the specificity of the intact active collagenase (M(r) 64,000), but the ability to cleave collagen was lost. The enzymic activity of this fragment can be inhibited by either tissue inhibitor of metalloproteinase (TIMP)-1 or recombinant TIMP-2 in a 1:1 molar ratio. The C terminal part of the enzyme (M(r) 27,000), important for the binding reaction with collagen substrates, is involved in collagenolysis. PMID- 8489513 TI - Sensitive, hydrosoluble, macromolecular fluorogenic substrates for human immunodeficiency virus 1 proteinase. AB - Hydrosoluble macromolecular fluorogenic substrates specific for the human immunodeficiency virus 1 (HIV-1) proteinase have been prepared. The fluoresceinyl peptide Ftc-epsilon-Ahx-Ser-Phe-Asn-Phe-Pro-Gln-Ile-Thr-(Gly)n, corresponding to the first cleavage site of HIV-1 gag-pol native precursor was linked to a water soluble neutral (Lys)n derivative. The epsilon-aminohexanoyl residue (epsilon Ahx) and the glycyl sequence were added in order to improve the stability of the substrate and the accessibility of the cleavage site to the HIV-1 proteinase respectively. This macro-molecular peptidic-substrate conjugate is significantly more water-soluble than the free peptide itself on a substrate molar concentration basis. The assay is based on the quantitative precipitation of the polymeric material by adding propan-2-ol whereas the fluorescent peptide moiety released upon proteolysis remains soluble in the supernatant. The proteinase activity is assessed by measuring the fluorescence of the supernatant. This assay allows the detection of a few fmol of HIV-1 proteinase, even in the presence of cell culture media, plasma or cell lysate and it gives accurate results within a large proteinase concentration range. The hydrosoluble macromolecular substrate is also suitable for determining the HIV-1 proteinase activity using 96-well microplates, allowing us to test accurately and rapidly numerous enzyme samples and/or the potency of new proteinase inhibitors. PMID- 8489514 TI - Hydrolyses of alpha- and beta-cellobiosyl fluorides by cellobiohydrolases of Trichoderma reesei. AB - Cellobiohydrolase II hydrolyses alpha- and beta-D-cellobiosyl fluorides to alpha cellobiose at comparable rates, according to Michaelis-Menten kinetics. The stereochemistry, absence of transfer products and strict hyperbolic kinetics of the hydrolysis of alpha-cellobiosyl fluoride suggest that the mechanism for the alpha-fluoride may be the enzymic counterpart of the SNi reaction observed in the trifluoroethanolysis of alpha-glucopyranosyl fluoride [Sinnott and Jencks (1980) J. Am. Chem. Soc. 102, 2026-2032]. The absolute factors by which this enzyme accelerates fluoride ion release are small and greater for the alpha-fluoride than for the beta, suggesting that its biological function may not be just glycoside hydrolysis. Cellobiohydrolase I hydrolyses only beta-cellobiosyl fluoride, which is, however, an approx. 1-3% contaminant in alpha-cellobiosyl fluoride as prepared and purified by conventional methods. Instrumental assays for the various components of the cellulase complex are discussed. PMID- 8489515 TI - N.m.r. spectroscopic studies of fucose-containing oligosaccharides derived from keratanase digestion of articular cartilage keratan sulphates. Influence of fucose residues on keratanase cleavage. AB - Keratan sulphate chains from bovine articular cartilage were fully digested with keratanase from Pseudomonas sp. and the products were reduced with alkaline borohydride. The resultant fragments were fractionated on a Nucleosil 5SB column and the earliest eluting fucose-containing oligosaccharides were isolated. Structural analysis using 1H n.m.r. spectroscopy (600 MHz) showed the two least charged species to have the following structure: GlcNAc(6S) beta 1-3Gal beta 1 4(Fuc alpha 1-3)GlcNAc(6S) beta 1- 3Gal beta 1-4GlcNAc(6S) beta 1-3Gal-ol and GlcNAc(6S) beta 1-3Gal beta 1- 4(Fuc alpha 1-3)GlcNAc(6S) beta 1-3Gal beta 1 4GlcNAc(6S) beta 1-6(Gal beta 1- 3)GalNAc-ol. Both galactoses adjacent to the fucosylated N-acetylglucosamine residue are unsulphated. Therefore, it can be deduced from these structures that the presence of fucose on N-acetylglucosamine residues in keratan sulphates protects both of the adjacent unsulphated galactose residues from keratanase cleavage. This result has implications for the interpretation of keratanase fingerprints, because in articular cartilage keratan sulphates the keratanase-resistant blocks are not solely those with fully sulphated galactose residues, but also include the fucosylated sequences, which have unsulphated galactoses. It is, therefore, not possible to estimate their galactose sulphation or the size of the fully sulphated disaccharide-repeat sequences from keratan sulphates that contain fucose. PMID- 8489516 TI - Formylmethionyl-leucylphenylalanine and the SOS operon in Escherichia coli: a model of host-bacterial interactions. AB - To determine the biological significance of the existence of highly specific receptors for the bacterial chemotactic peptide formylmethionyl leucylphenylalanine (fMet-Leu-Phe) on neutrophil leucocytes, we investigated the role of this peptide in bacterial metabolism. The UmuD protein of the Escherichia coli SOS operon was identified as having an N-terminal fMet-Leu-Phe sequence and a recombinant E. coli with the umuD gene on plasmid pSB13 was shown to be an over producer of both UmuD and fMet-Leu-Phe. Activation of SOS genes in conventional wild-type E. coli (K12) by u.v. light or hydrogen peroxide increased fMet-Leu-Phe production up to 4-fold. A RecA- strain, incapable of SOS activation, was a low basal producer of fMet-Leu-Phe and showed no increased production with u.v. light or oxidant stress. We propose that host phagocytes respond to fMet-Leu-Phe and closely related peptides because they are generated by bacteria under oxidant stress. Increased fMet-Leu-Phe production may signal to the host a change in the organism's biological status from commensal to pathogen because of the invasion into tissues exposing bacteria to high pO2 levels and oxidant stress. PMID- 8489517 TI - Inactivation of penicillin acylase from Kluyvera citrophila by N-ethoxycarbonyl-2 ethoxy-1,2-dihydroquinoline: a case of time-dependent non-covalent enzyme inhibition. AB - Penicillin acylase (PA) from Kluyvera citrophila was inhibited by N ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a specific carboxy-group reactive reagent. Enzyme activity progressively decreased to a residual value depending on EEDQ concentration. Neither enzymic nor non-enzymic decomposition of EEDQ is concomitant with PA inactivation. Moreover, enzyme re-activation is achieved by chromatographic removal of EEDQ, pH increase or displacement of the reagent with penicillin G. It was then concluded that PA inactivation is due to an equilibrium reaction. The kinetics of enzyme inactivation was analysed by fitting data to theoretical equations derived in accordance with this mechanism. Corrections for re-activation during the enzyme assay were a necessary introduction. The pH-dependence of the rate constant for EEDQ hydrolysis either alone or in the presence of enzyme was studied by u.v. spectroscopy. It turned out to be coincident with the pH-dependence of the forward and reverse rate constants for the inactivation process. It is suggested that previous protonation of the EEDQ molecule is required for these reactions to occur. The thermodynamic values associated with the overall reaction showed little change. Finally it is proposed that the inactivation of PA by EEDQ proceeds through a two-step reaction. The initial and rapid reversible binding is followed by a slow, time dependent, non-covalent, reversible inactivating step. The expected behaviour in the case of enzyme modification by covalent activation of carboxy residues is also reviewed. PMID- 8489518 TI - The interaction of phospholipid bilayers with pig heart AMP deaminase: Fourier transform infrared spectroscopic and kinetic studies. AB - The interaction of pig heart AMP deaminase with different chemical species of phosphatidylcholine and with natural plasma membranes has been investigated. Phospholipids added to the system either as natural biological membranes (plasma membrane vesicles) or in the form of liposomes containing unsaturated phosphatidylcholine considerably enhanced AMP deaminase activity. The secondary structure of pig heart AMP deaminase in the absence and in the presence of dioleoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine liposomes was investigated by Fourier-transform infrared spectroscopy. Quantitative analysis of the amide I band showed that the enzyme contains 45% beta-sheets, 28% alpha helix, 16% turns and 11% non-ordered structure. In the presence of dioleoyl phosphatidylcholine liposomes, the beta/alpha content ratio decreased; this decrease was dependent on the amount of lipid added. This phenomenon was not observed in the case of dipalmitoyl phosphatidylcholine liposomes. These data suggest a possible role for membrane phospholipids in the regulation of AMP deaminase activity. PMID- 8489519 TI - 8-vinyl reduction and chlorophyll a biosynthesis in higher plants. AB - A technique involving solid-phase extractions and polyethylene h.p.l.c. suitable for the routine compositional analysis of the total protochlorophyllide pool of plants is described. The resynthesis kinetics of the individual components of the pool have been studied in briefly illuminated etiolated tissue of wheat (Triticum aestivum) and cucumber (Cucumis sativus) during subsequent redarkening. The data are interpreted in terms of a precursor-product relationship between the di- and mono-vinyl analogues of protochlorophyllide during their reaccumulation in darkness. The interconversion is assumed to be catalysed by an 8-vinyl reductase, which shows greater activity in wheat than in cucumber. Analyses of the redox state of the nicotinamide nucleotide of the pool during the process are compatible with NADPH as the cofactor of the putative reductase. PMID- 8489521 TI - Hyaluronan-binding region of aggrecan from pig laryngeal cartilage. Amino acid sequence, analysis of N-linked oligosaccharides and location of the keratan sulphate. PMID- 8489520 TI - The role of Gi and the membrane-fluidizing agent benzyl alcohol in modulating the hysteretic activation of human platelet adenylate cyclase by guanylyl 5' imidodiphosphate. AB - The non-hydrolysable GTP analogue guanylyl 5'-imidodiphosphate (p[NH]ppG) elicited a profound increase in the adenylate cyclase activity of human platelets. This occurred after a well-defined lag period of around 6 min, whereupon an enhanced steady-state rate was evident. The duration of the lag period was unchanged over a range of concentrations of p[NH]ppG which gave very different steady-state rates of adenylate cyclase activity. Prior activation of the stimulatory G-protein Gs by cholera-toxin pre-treatment abolished the lag period and elicited a small increase in the steady-state rate. Manipulating function of the inhibitory G-protein Gi also led to profound changes in the lag periods. Thus marked decreases in the lag were seen (approximately 70-81%) when Gi function was ablated through pre-treatment of platelet membranes with pertussis toxin, or by using elevated (25 mM) Mg2+ levels in the assay, or when Mg2+ was replaced by 5 mM Mn2+ in the assay. In contrast with this, potentiation of Gi function led to an increase in the lag period, as seen under conditions of agonist occupancy of inhibitory alpha 2-adrenoceptors (increase approximately 74%) or with the addition of 100 mM NaCl to the assays (increase approximately 44%). The local anaesthetic and membrane-fluidizing agent benzyl alcohol elicited both a profound decrease (around 70% at 80 mM) in the p[NH]ppG-induced lag period and a marked augmentation (around 5-fold) in the steady-state adenylate cyclase activity. When adenylate cyclase assays were done at 35 degrees C instead of 25 degrees C, then the lag period for activation by p[NH]ppG was decreased by around 33% and the steady-state rate increased by around 3-fold. At 35 degrees C, the addition of benzyl alcohol led to the apparent abolition of the lag period for p[NH]ppG activation of adenylate cyclase and amplified the steady-state rate by only around 2.2-fold. It is shown that Gi plays a fundamental role in determining the rate of activation of Gs. The proposal is formulated that such an action may be mediated through the release of beta gamma-subunits. Thus beta gamma-subunit dissociation is proposed as providing the rate-limiting step in Gi activation. PMID- 8489522 TI - Cyclin synthesis: who needs it? AB - Studies of the G2 to M transition in amphibian oocytes, in combination with in vitro mitotic systems and yeast genetic analysis, have significantly contributed to our understanding of the mechanisms by which M-phase is regulated. Historically, oocyte maturation has provided a number of valuable initial observations, but the biochemical elucidation of cell cycle control mechanisms has proved more tractable in cell-free extracts of frog eggs which reproduce aspects of early embryogenic mitosis. Recent experiments examining the importance of protein synthesis in the maturing oocyte have highlighted some important differences between mitosis and meiosis. Additional controls found in meiosis but not embryonic mitosis, are similar to controls found in somatic cells. This suggests that understanding the differences, as well as the similarities, between meiosis in the oocyte and mitosis in the early embryo will help us to learn more about the way in which cells enter and leave mitosis. PMID- 8489523 TI - Pre-mRNA secondary structure and the regulation of splicing. AB - Nuclear pre-mRNAs must be precisely processed to give rise to mature cytoplasmic mRNAs. This maturation process, known as splicing, involves excision of intron sequences and ligation of the exon sequences. One of the major problems in understanding this process is how splice sites, the sequences which form the boundaries between introns and exons, can be accurately selected. A number of studies have defined conserved sequences within introns which were later shown to interact with small nuclear ribonucleoproteins (snRNPs). However, due to the simplicity of these conserved sequences it has become clear that other elements must be involved and a number of studies have indicated the importance of secondary structures within pre-mRNAs. Using various examples, we shall show that such structures can help to specify splice sites by modifying physical distances within introns or by being involved in the definition of exons and lastly, that they can be part of the regulation of alternative splicing. PMID- 8489524 TI - Vav: a potential link between tyrosine kinases and ras-like GTPases in hematopoietic cell signaling. AB - The vav proto-oncogene encodes a 95 kDa protein which is expressed exclusively in hematopoietic cells. Analysis of the deduced amino acid sequence has revealed the presence of a src-homology 2 (SH2) domain, 2 SH3 domains, a cysteine-rich region with similarity to protein kinase C, and a region highly similar to proteins with guanine nucleotide exchange activity on ras-like GTPases. Recent work has shown that vav is tyrosine phosphorylated in response to stimulation of surface membrane receptors in a variety of hematopoietic cell lines. Vav may play a role in hematopoietic cell signaling by coupling tyrosine kinase pathways to ras-like GTPases through the regulation of guanine nucleotide exchange. PMID- 8489525 TI - Cell commitment in the ectoderm of Drosophila melanogaster. PMID- 8489526 TI - The telophase disc: its possible role in mammalian cell cleavage. AB - The molecular signals that determine the position and timing of the furrow that forms during mammalian cell cytokinesis are presently unknown. It is apparent, however, that these signals are generated by the mitotic spindle after the onset of anaphase. Recently we have described a structure that bisects the cell during telophase at the position of the cytokinetic furrow. This structure, the telophase disc, appears to be templated by the mitotic spindle during anaphase, and precedes the formation of the cytokinetic furrow. The relationship of the telophase disc to the myosin and actin based furrowing mechanism is discussed here. We propose that the telophase disc may determine the position and timing of cleavage by recruitment and alignment of myosin. PMID- 8489527 TI - Fine tuning of DNA repair in transcribed genes: mechanisms, prevalence and consequences. AB - Cells fine-tune their DNA repair, selecting some regions of the genome in preference to others. In the paradigm case, excision of UV-induced pyrimidine dimers in mammalian cells, repair is concentrated in transcribed genes, especially in the transcribed strand. This is due both to chromatin structure being looser in transcribing domains, allowing more rapid repair, and to repair enzymes being coupled to RNA polymerases stalled at damage sites; possibly other factors are also involved. Some repair-defective diseases may involve repair transcription coupling: three candidate genes have been suggested. However, preferential excision of pyrimidine dimers is not uniformly linked to transcription. In mammals it varies with species, and with cell differentiation. In Drosophila embryo cells it is absent, and in yeast, the determining factor is nucleosome stability rather than transcription. Repair of other damage departs further from the paradigm, even in some UV-mimetic lesions. No selectivity is known for repair of the very frequent minor forms of base damage. And the most interesting consequence of selective repair, selective mutagenesis, normally occurs for UV-induced, but not for spontaneous mutations. The temptation to extrapolate from mammalian UV repair should be resisted. PMID- 8489528 TI - [Localization of an immunodominant site in the hepatitis delta viral antigen using synthetic peptides]. AB - A set of 8 peptides from the immunodominant region (65-80 aa) of delta-antigen was prepared by solid-phase synthesis. Peptide 71-80 was synthesized in two variants--with different amino acid residues in positions 73, 74 and 76. Free peptides and their conjugates with bovine serum albumin were tested for antigenicity in ELISA. The correlation between the peptide chain's length and its antigenic activity was noted. Peptides 65-80 and 69-80 displayed a positive reaction with all individual sera and pools of sera from HDV chronic patients. Both variants of the peptide 71-80 reacted with 100% of sera pools but only with 83% of individual sera. Smaller peptides from the same 65-80 region (73-80, 69 78, 71-78, 71-76) did not bind to any anti-delta positive serum. All synthesized peptides reacted strongly with rabbit antisera raised to the conjugate of peptide 65-80 with bovine albumin. These findings suggest that delta-antigen contains multiple highly immunogenic epitopes associated with the single immunodominant site between 69 and 80 amino acid residues. PMID- 8489529 TI - [Preparation, isolation, and study of mutant forms of ribosomal protein L7/L12]. AB - Three mutant forms of the ribosomal protein L7/L12 with Ser1, Met14 and Met26 substituted by the Tyr residue were constructed for studying the protein's N terminal domain. Three point mutations were introduced into the L7/L12 gene by means of the phage M13mp18 system, the mutant genes were expressed in Escherichia coli cells, and methods of the proteins' purification were developed. The mutant proteins L7/L12 are very close, in structure and properties to the wild type protein and represent suitable objects for the 1H-NMR study of the N-terminal domain. PMID- 8489530 TI - [Structure of molecules of crystalline (Phe1, Ala9)antamanide]. AB - The molecular structure of a [Phe1, Ala9]antamanide complex with four water molecules has been determined by X-ray analysis. The antamanide's analogue, C64H74N10O10.4H2O, crystallizes in the space group P2(1)2(1)2(1) with a = 15.909, b = 28.071 and c = 14.367 A, Z = 4. The molecule contains a pseudo two-fold rotation axis and two intra-molecular NH...O = C bonds of the 5-->1 type, its conformation being similar to that of antamanide. There are inter-molecular H bonds over the water molecules in the structure. PMID- 8489531 TI - [Affinity modification of 40S ribosomal subparticles from human placenta with mRNA analogs--AUGUnC oligoribonucleotide analogs with an alkylating group at the 3'-end]. AB - Using 2',3'-O-[4-N-(2-chloroethyl)-N-methylamino]benzylidene derivatives of AUGUn[32P]pC (mRNA analogues), affinity labelling of human placenta 40S ribosomal subunits has been investigated in model initiation complexes obtained in the presence of the ternary complex eIF-2.GTP.Met-tRNA(fMet). The regions of 18S rRNA labelled with these mRNA analogues were identified. The main targets of 18S rRNA alkylation by the derivative of AUG[32P]pC were located within positions 1610 1747 and 1748-1869. The site of covalent attachment of AUGU3[32P]pC derivative to 18S rRNA was found within positions 593-673. Taking into account the data on labelling of human placenta ribosomes with the same derivatives of oligourydilates obtained previously, the conclusion was made that the arrangement of the codon U3 in the mRNA-binding centre of the initiation complex 40S.AUGU3[32P]pC derivative.eIF-2.GTP.Met-TPHK(fMet) differs from the arrangement of the same codon at the A-site of the complex imitating the pretranslocation state of ribosomes. PMID- 8489532 TI - [Use of hydrazine for rapid deblocking of synthetic oligonucleotides]. AB - A rapid method for the removal of protecting groups from synthetic oligodeoxyribonucleotides, obtained by the phosphoroamidite and H-phosphonate methods, including the use of hydrazine solutions has been developed. The combination of this procedure with the application of isopropoxyacetyl N protecting group and oxalyl ester linkage for the first nucleoside attachment to the polymer support allows to reduce to several minutes the time needed for the full oligonucleotide deprotection. PMID- 8489533 TI - [Structure of the repeating link of the acid polysaccharide of Alteromonas haloplanktis KMM 156]. AB - An acidic capsular and an O-specific polysaccharide were isolated from the marine microorganism Alteromonas haloplanktis KMM 156. Both polysaccharides have the identical structure and are built up of tetrasaccharide repeating units, containing two residues of L-rhamnose as well as a 2-acetamido-2-deoxy-D-glucose and a 3-O-[(R)-1-carboxyethyl]-D-glucose (Glc3Lac) residue. On the basis of methylation studies, 1H- and 13C-NMR-spectroscopy including nuclear Overhauser effect and two-dimensional heteronuclear 13C/1H correlation spectroscopy, the following structure was suggested for the polysaccharide repeating unit: [formula: see text] PMID- 8489534 TI - [Synthesis of platelet activation factor analogs]. AB - Novel structural analogues of the platelet activating factor (PAF), rac-1 octadecyl-2-allyl-glycerol-3-phosphocholine and rac-1-octadecyl-2-allyl-1 thioglycerol-3-phosphocholine , have been synthesized. The phospholipids obtained showed neither PAF-agonistic nor PAF-antagonistic activity at the concentration of 10(-5) to 10(-7) M. PMID- 8489535 TI - [Use of arylsulfenylchlorides for cleaving fibrinogen at methionine residues]. AB - Conditions for the fibrinogen fragmentation with 2-pyridyl-or o nitrophenylsulfenylchloride were proposed. Resulting mixture of fragments is identical to the mixture prepared by the cyanogen bromide treatment and is suitable as supplementary analytical reagent in the determination of the tissue plasminogen activator (TPA) activity with a chromogenic substrate. PMID- 8489536 TI - AI/LEARN/Rheumatology. A comparative study of computer-assisted instruction for rheumatology. AB - OBJECTIVE: To assess the effectiveness of AI/LEARN/Rheumatology, a computer controlled interactive videodisc system for teaching. METHODS: We assessed improvement in knowledge about rheumatic diseases, using a pretest and posttest in a control year and a treatment year. The subjects were medical students and postgraduate trainees taking the rheumatology elective. The control year used traditional lectures and the standard rheumatology curriculum. The treatment year used AI/LEARN/Rheumatology in place of lectures on rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. RESULTS: The trainees showed significant improvement in knowledge in both the control year and the treatment year (P < 0.0001 for both). The average time spent using AI/LEARN/Rheumatology was similar to the time spent in lectures (3 hours). The number of patient consultations in which trainees participated was lower in the treatment year than in the control year; however, the adjusted posttest scores using the pretest as a covariate tended to be higher in the treatment year (P = 0.10). Analysis of covariance of the adjusted posttest scores for the treatment year only showed that the trainees who spent more time using AI/LEARN/Rheumatology learned more (r = 0.57). Trainees felt that AI/LEARN/Rheumatology was the most helpful educational experience of the elective. CONCLUSION: AI/LEARN/Rheumatology is an effective means of teaching about the rheumatic diseases. It has many advantages: availability for independent study, effective use of trainee's time, and liberation of faculty time from lectures. Trainees enjoyed using AI/LEARN/Rheumatology. PMID- 8489537 TI - Marital status and the progression of functional disability in patients with rheumatoid arthritis. AB - OBJECTIVE: To determine if marital status is associated with differences in rates of progression of functional disability in patients with rheumatoid arthritis (RA). METHODS: A community cohort of 282 persons with RA was followed prospectively for up to 9.5 years. The progression of functional disability over time was determined using the Health Assessment Questionnaire Disability Index, which was completed by study participants every 6 months. RESULTS: At study entry, the Disability Index was 1.1 +/- 0.8 (mean +/- 1 SD) (possible range 0-3) among the 188 married participants and 1.3 +/- 0.9 among the 94 unmarried participants. Over time, the rate of progression of functional disability was generally higher among unmarried participants. However, the extent of this difference varied somewhat over the disease course, with rates of progression higher among unmarried than among married participants during years 5-7 and years 17-29 of RA. Overall estimated rates of progression, adjusted for the effects of other sociodemographic factors, were 0.03 Disability Index units per year in unmarried participants and 0.01 Disability Index units per year in married participants (P < 0.0001). CONCLUSION: Marriage, possibly reflecting the influence of social support, is associated with a lower rate of progression of functional disability in persons with RA. PMID- 8489538 TI - Marital status and social support in rheumatoid arthritis. PMID- 8489539 TI - The effects of drug therapy on radiographic progression of rheumatoid arthritis. Results of a 36-week randomized trial comparing methotrexate and auranofin. AB - OBJECTIVE: To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA). METHODS: We conducted a 9-month randomized, multicenter, double blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation. RESULTS: Two hundred eighty-one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean +/- SEM change of 1.67 +/- 0.4) compared with the change in the MTX group (0.60 +/- 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 +/- 0.3 versus 0.42 +/- 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation. CONCLUSION: The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period. PMID- 8489540 TI - Analysis of immunoglobulin gamma heavy chain expression in synovial tissue of a patient with rheumatoid arthritis. AB - OBJECTIVE: To gain insight into mechanisms underlying local immune responses in rheumatoid arthritis (RA), we analyzed the utilization of variable-region heavy chain (VH), diversity (DH), and joining (JH) gene segments expressed in synovial tissue of a patient with RA. METHODS: An unrestricted complementary DNA (cDNA) library was generated from unselected cells extracted from synovial tissue obtained at the time of joint replacement. Southern blot analysis for VH, JH, and C gamma subclass utilization was performed on the first 50 C gamma- and JH positive recombinants for which phage DNA was isolated. Eighteen of the clones were selected at random for sequence analysis. The VH gene segments were compared with an extensive database of germline and cDNA sequences. RESULTS: All transcripts utilized gene segments from the VH1 (28%), VH3 (56%), and VH4 (15%) families. There was a predominance of JH4, JH5, and JH6 gene segment utilization. Fourteen of 18 randomly sequenced clones contained sufficient VH-region information for analysis. Eight (57%) were most closely related to VH gene segments that are preferentially expressed in human fetal liver or that encode antibodies with self-reactivity. The variable domains were heavily mutated, and replacement-to-silent substitution ratios (R:S ratios) in the antigen-binding domains (complementarity-determining regions [CDRs]) were disproportionately high. CDR3 lengths were quite variable, due to extensive N-region addition and 5' exonuclease activity in the VH-DH-JH joins. CONCLUSION: Plasma cells in this synovial tissue sample appear to express VH gene segments that are preferentially utilized during fetal development or in autoantibodies. The JH repertoire is similar to that seen in adult peripheral blood lymphocytes, but much different from that found during fetal development. The large number of somatic mutations and the high R:S ratios in the CDRs suggest an antigen-driven response. PMID- 8489541 TI - Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. AB - OBJECTIVE: We hypothesized that change in pain threshold to pressure reflects a generalized change in the pain system affecting both tender and control points. METHODS: We assessed 18 tender points and 4 control points using an algometer in 60 patients with generalized fibromyalgia/fibrositis syndrome, 60 patients with localized chronic pain syndromes, and in 60 pain-free subjects. RESULTS: A significant correlation was found between myalgia scores at tender points and control points in these subjects. CONCLUSION: These results suggest that there is a diffuse change in pain modulation in fibromyalgia, as hypothesized, but the tender point is still clinically useful. PMID- 8489542 TI - The spectrum of fibromyalgia disorders. PMID- 8489543 TI - Characteristics of anti-type II collagen antibody binding to articular cartilage. AB - OBJECTIVE: Previous studies suggested that it was possible to characterize the intact surface of articular cartilage by probing it with antibodies against matrix macromolecules. The present studies were undertaken to investigate type II collagen (CII) epitope availability on the intact surface of articular cartilage. METHODS: Normal bovine, rabbit, and human cartilage specimens were used to measure binding of anti-CII antibodies to the articular and cut surfaces of cartilage. Antisera were raised against the material obtained after brief extraction of the cartilage surface with 4M guanidine solution. RESULTS: Anti-CII did not bind to the intact surface of rabbit articular cartilage when compared with control rat sera, but did bind significantly to the cut surface. With normal human articular cartilage, the cut surfaces bound approximately 4 times as much anti-CII antibody as the intact articular surfaces. These findings suggested that the CII epitopes are normally protected by the superficial cartilage layer. In experiments carried out to characterize this layer, binding of anti-CII antibodies was unchanged after exhaustive washing of bovine or rabbit cartilage with phosphate buffered saline or 1M NaCl solution, whereas it was significantly increased after brief exposure to 4M guanidine solution or after incubation with neutrophil elastase. No restoration of the protection of CII epitopes in guanidine-treated cartilage could be achieved by incubation with undiluted normal bovine synovial fluid; however, 8-day culture of elastase-treated cartilage explants resulted in partial restoration of protection of the CII epitopes. Rat and rabbit antisera raised against the cartilage surface material extracted with 4M guanidine contained antibodies that bound to the cartilage surface. By Western blotting, rat antibodies identified 50-65-kd protein bands present in the guanidine extract, but not present either in the material obtained from brief digestion of cartilage with neutrophil elastase or in synovial fluid. The rabbit antisera identified a broad 70-95-kd band. Exposure of elastase-treated cartilage to the guanidine-extracted material resulted in a partial decrease of anti-CII antibody binding. CONCLUSION: These results suggest that CII on intact cartilage is protected from antibody binding, and that the protective material is at least partly proteinaceous in nature, is unlikely to be derived from synovial fluid, is noncovalently bound to the underlying intercellular matrix, and is synthesized by resident chondrocytes. Further characterization of the protective material may provide important information on the mechanisms of early cartilage damage in inflammatory arthritis. PMID- 8489544 TI - Susceptibility to relapsing polychondritis is associated with HLA-DR4. AB - OBJECTIVE: To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP). METHODS: HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement-dependent microcytotoxicity assay. HLA-DR genotyping of 12 DR4-positive RP patients and 57 controls was performed by allele-specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction. RESULTS: A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (Pcorr < 0.001). Genotyping of DR4-positive patients and controls revealed no predominance of any DR4 subtype. CONCLUSION: There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions. PMID- 8489545 TI - The polymerase chain reaction for the detection of Borrelia burgdorferi in human body fluids. AB - OBJECTIVE: To analyze clinical fluids for the presence of Borrelia burgdorferi DNA using the polymerase chain reaction (PCR). METHODS: We utilized a modified, nested PCR to detect the presence of Borrelia DNA in 99 samples of serum, urine, cerebrospinal fluid (CSF), or synovial fluid obtained from 44 patients with various stages of Lyme disease and 47 control subjects. Primer specificity was corroborated by examining 2 DNA data banks, testing against DNA from other organisms, and confirming results with a second set of nested primers. RESULTS: Nested PCR was capable of detecting DNA from fewer than 10 organisms in 1 ml of fluid. The specificity of this technique was 96.4%, with a sensitivity of 76.7%. Although the specificity was uniformly high, the sensitivity was dependent upon the body fluid being tested: CSF 100%, urine 100%, synovial fluid 80%, and serum 59%. The rate of false-positive results was 3.6%. CONCLUSION: These data demonstrate the potential utility of PCR in confirming the clinical diagnosis of Lyme disease as well as providing insight into the pathogenesis of various stages of this disorder. PMID- 8489546 TI - Familial versus sporadic ankylosing spondylitis. Two different diseases? AB - OBJECTIVE: To define potential differences and the possible contribution of susceptibility or severity genes in familial versus sporadic ankylosing spondylitis (AS). METHODS: Three hundred twenty patients with AS were studied: 160 who had first-degree relatives with AS (familial) and 160 age- and sex matched controls who had no first-degree relative with the disease (sporadic). Disease expression in the two groups was evaluated using an index of physical, psychological, and social functioning (the Arthritis Impact Measurement Scales [AIMS]) and an assessment of spinal mobility. RESULTS: Familial disease was significantly milder than sporadic disease as assessed by all measures, e.g., spinal mobility score (mean 4.08 versus 4.65, P < 0.038), AIMS overall impact score (mean 2.63 versus 3.59, P = 0.002), AIMS physical activity score (4.19 versus 5.10 [P = 0.004]), AIMS social function score (4.02 versus 4.60, P = 0.023), and AIMS pain score (4.15 versus 5.33, P = 0.002). CONCLUSION: The greater prevalence of AS in at-risk families may be explained by the occurrence of more AS "susceptibility" genes in those families, whereas the more severe disease, seen in patients with sporadic AS, is conferred by the presence of more "severity" genes than "susceptibility" genes. PMID- 8489547 TI - Treatment of refractory, systemic lupus erythematosus-associated thrombocytopenia with intermittent low-dose intravenous cyclophosphamide. AB - We describe a patient with systemic lupus erythematosus and severe, treatment resistant thrombocytopenia. Prolonged treatment with high-dose steroids eventually led to reversal of the thrombocytopenia, but the dosage could not be tapered without relapse. Low-dose intravenous bolus cyclophosphamide was given, producing a response within 1 week. The steroid dosage was tapered, without relapse. Other than reversible alopecia, no toxicity was seen. The use of this treatment should be considered in patients in whom more conventional therapies are not effective or cannot be tolerated. PMID- 8489548 TI - Gastrointestinal regulatory peptides in systemic sclerosis. AB - OBJECTIVE: Gastrointestinal involvement commonly occurs in systemic sclerosis (SSc), but its pathogenesis is not well understood. Since there is evidence of a defect in neurotransmitter release, we were interested in examining the relationship between gastrointestinal dysfunction and plasma concentrations of gastrointestinal regulatory peptides in patients with SSc. We studied 43 consecutive patients, 18 with diffuse and 25 with limited cutaneous disease. METHODS: Levels of corticotropin-releasing hormone (CRH), gastrin, motilin, neuropeptide Y (NPY), and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC). RESULTS: Plasma concentrations of CRH, motilin, NPY, and PYY were significantly increased among SSc patients compared with healthy control subjects, and HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments. No correlation was found between esophageal hypomotility and the concentration of peptide. Acid output did not correlate with gastrin levels, but was more often increased in patients with increased CRH and NPY values. Fat malabsorption, assessed by the triolein breath test, was more common among patients with increased motilin and PYY. CONCLUSION: This study shows that elevated peptide concentrations commonly occur in patients with SSc. Since regulatory peptides are involved in gastrointestinal motility, secretion, and absorption, further characterization of this neuroendocrine system may help in understanding the complex regulation of gastrointestinal dysfunction in SSc. PMID- 8489549 TI - Calcium pyrophosphate dihydrate crystal deposition in synovium. Relationship to collagen fibers and chondrometaplasia. AB - OBJECTIVE: Reasons for apparent primary deposition of calcium pyrophosphate dihydrate (CPPD) crystals in some synovial membranes have not been systematically examined. We undertook the present study to investigate for and compare possible cellular and matrix factors related to the presence of these crystals in synovium and cartilage. METHODS: Ten synovial membrane specimens and 6 cartilage specimens were obtained at the time of joint surgery from 10 patients with CPPD crystal deposition disease, for light microscopic (LM) and electron microscopic (EM) studies. RESULTS: In all synovial and cartilage specimens, we found many of the small CPPD crystals aligned on or in parallel to collagen fibers, as seen by EM. In 9 of the 10 crystal-containing synovia, we found foci of chondrometaplasia adjacent to CPPD, by LM. In 7 of the synovia, including the one without LM evidence of chondrometaplasia, we observed the presence of chondrocyte-like cells by EM. We did not note any predictable relationship between the crystals and matrix vesicles, either in synovium or in cartilage. CONCLUSION: Our EM findings provide evidence of the relationship of small CPPD-like crystals, presumably early forms, to collagen fibers both in synovium and in cartilage. By LM and EM, we also demonstrate evidence of a close association between chondrometaplasia and CPPD deposits in synovium. We suggest that chondrometaplasia might be responsible for synovial CPPD formation in predisposed patients. Both the collagen fibers and chondrocyte-like cells seem to be involved in the primary formation of CPPD deposits in the synovium as well as in the cartilage. PMID- 8489550 TI - Sarcoidosis accompanied by pulmonary tuberculosis and complicated by sacroiliitis. AB - We report the unique occurrence of a unilateral sacroiliitis in a patient with active sarcoidosis accompanied by pulmonary tuberculosis. Convincing (clinical) evidence of sarcoidosis as the extremely rare cause of this articular involvement is presented. Discussion is focused on comparison of sarcoidosis and tuberculosis, particularly with respect to their articular involvement, and the literature of previously reported cases of sarcoid sacroiliitis is briefly reviewed. PMID- 8489551 TI - Colchicine and mixed cryoglobulinemia. PMID- 8489552 TI - Treatment with anti-CD4 monoclonal antibody and acute interstitial nephritis. PMID- 8489553 TI - The watermelon stomach in scleroderma. PMID- 8489554 TI - Dopamine agonist activities of pergolide, its metabolites, and bromocriptine as measured by prolactin inhibition, compulsive turning, and stereotypic behavior. AB - Four pergolide metabolites and bromocriptine (CAS 25614-03-3) were compared to pergolide (8 beta-[(methylthio) methyl]-6-propyl-ergoline, CAS 66104-22-1) using three in vivo animal models of activity at dopamine receptors. The results obtained from these studies of prolactin inhibition, induction of compulsive turning, and stimulation of stereotypic behavior, were very consistent. Two of the metabolites, despropyl pergolide and despropyl pergolide sulfoxide, were devoid of dopamine-like effects in any of the models. Pergolide sulfone and pergolide sulfoxide, however, were found to be potent dopamine agonists, similar in activity to pergolide itself. Dopamine D2 receptors (and probably D1 receptors also) appear to be involved in the activities of these compounds. The compounds were active by both oral and i.p. routes of administration. Bromocriptine, while possessing some dopamine agonist activity at higher doses in some of these animal models, was much less potent (1/200 to 1/20) than either pergolide or its two dopaminergic metabolites. PMID- 8489555 TI - Disposition of remoxipride in different species. Species differences in metabolism. AB - The pharmacokinetics and metabolism of the new antipsychotic agent remoxipride ((S)-(-)-3-bromo-N(-)[(1-ethyl-2-pyrrolidinyl)methyl]-2, 6-dimethoxybenzamide, FLA731(-), Roxiam, CAS 80125-14-0) was studied in rodents (mice, rats, hamsters), dogs and human subjects using the unlabelled or the labelled (3H or 14C) drug. Oral administration of 20-40 mumol/kg to animals and approximately 3 mumol/kg to human volunteers showed that the absorption of remoxipride through the intestinal wall was rapid and almost complete in all species. However, the bioavailability was low in the rodents (< 10% in mice and hamsters and < 1% in rats) due to an extensive first-pass elimination in the hepato-portal system. Blood clearance estimated after the same intravenous doses was high in rodents and similar to or exceeding normal liver blood flow. In dogs and humans, clearance values were low and the bioavailability high (> 90%). In mice and rats the contribution of renal clearance to the total clearance was approximately 10%, while it was higher in dogs (approximately 15%) and humans (approximately 30%). Species differences were also observed in the degree of protein binding which was low in rodent plasma (20 30%) but fairly high in canine and human plasma (approximately 80%). In dogs and humans, remoxipride was shown to bind primarily to the plasma alpha 1-acid glycoprotein fraction. In accordance with the binding data, the volume of distribution (Vss) was higher in rodents (3-6 l/kg) than in dogs (1.6 l/kg) and man (0.7 l/kg). Studies in dogs with 14C-remoxipride showed that the compound was rapidly distributed to tissues and eliminated at rates similar to that in plasma (t1/2 3-4 h). Retention of radioactivity was only observed in melanin-rich tissues. However, studies in pigmented mice showed that the affinity of remoxipride to melanin was lower than that of the other neuroleptics haloperidol and chlorpromazine. The excretion of radioactivity following oral administration of the labelled drug mainly occurred in the urine in all species. However, species differences were observed in the identification and analysis of the various metabolites present in plasma and excreted in urine. In rodents, metabolic reactions occurred mainly at the aromatic moiety, i.e. O-demethylation and aromatic hydroxylation. The resulting phenols were excreted mainly in conjugated forms. In dogs and humans, the predominant metabolic reactions were oxidations at the alpha-carbons of the pyrrolidine moiety leading to N demethylated and/or pyrrolidone and hydroxypyrrolidone products.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8489556 TI - Pharmacokinetics of and monoamine oxidase B inhibition by (E)-4-fluoro-beta fluoromethylene benzene butanamine in man. AB - MDL 72974A ((E)-4-fluoro-beta-fluoromethylene benzene butanamine HCl salt, CAS 120635-25-8) is a new irreversible inhibitor of the B form of monoamine oxidase (MAO-B). MDL 72974A's pharmacokinetic parameters were evaluated after administration of a single oral dose and after multiple oral doses. The concentration of parent drug was determined in plasma using a solid-liquid extraction method and gas chromatographic-mass spectrometric analysis. MDL 72974A produced significant inhibition of platelet MAO-B activity at all of the doses > or = 0.5 mg (> 95% after 1 h). The pharmacokinetic parameters showed a short plasma half-life (1 h) and a high total body clearance (Cltot) both probably due to extensive and rapid metabolism as suggested by the low urinary excretion of unchanged drug (< 1% of the administered dose). After the administration of multiple doses of MDL 72974A, a decrease in Cltot and a concomitant increase in the AUC and t1/2, was observed, probably due to a change in the elimination rate of MDL 72974A. Due to the once-a-day dosing schedule and the short plasma t1/2, no drug accumulation occurred. PMID- 8489557 TI - Electrophysiological characterization of class III activity of a verapamil derivative in guinea-pig cardiac tissues. AB - In isolated guinea-pig papillary muscle ([K+]o: 4.7 mmol/l, stimulation rate: 1 Hz) the verapamil derivative NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine)-HCl (YS035; 0.3-100 mumol/l) increased the action potential duration measured at 90% repolarization level (APD90) up to 132% of control and enhanced the force of contraction (Fc) up to 125% of control while resting potential (RP) and the maximum upstroke velocity (Vmax) remained nearly unchanged. At 300 mumol/l YS 035, the membrane became depolarised and action potentials could no longer be elicited. These effects were reversed during wash-out. The increase of ADP90 was largest at 0.05 Hz, and the drug-induced effect continuously declined with an increase in stimulation frequency to 2 Hz. Control ADP90 was correlated to the absolute increase of ADP90 (r = 0.84). In atrial muscle the effect of YS 035 on APD90 was more pronounced than in papillary muscle. The Vmax of slow responses ([K+]o: 27 mmol/l, [Ba2+]o: 0.5 mmol/l) was not affected by concentrations as high as 30 mumol/l YS 035, whereas APD90 was enhanced. An increase in the stimulation rate (0.05 to 0.33 Hz) induced only a small decrease of Vmax at 100 mumol/l YS 035. According to this electrophysiological characterisation YS 035 shows Class III antiarrhythmic properties. PMID- 8489559 TI - In vitro and in vivo studies on slow release propranolol hydrochloride suppositories. Pharmacokinetic and pharmacodynamic evaluation. AB - Matrix-based slow release (SR) compressed propranolol HCl (25 mg) suppositories were formulated using PEG 4000 and either stearic acid or bees wax at different concentrations (5, 7.5 and 10%). In vitro studies revealed good slow release characteristics from the suppositories. Their in vivo performances- pharmacokinetics and pharmacodynamics--were evaluated in rabbits. Different pharmacokinetic parameters were determined from the plasma concentration-time profiles using a model-independent computer programme, RAMKIN. The relative bioavailability of propranolol (CAS 525-66-6) from three SR suppositories containing stearic acid, 7.5 and 10% and bees wax, 5%, was 86.4, 87.8, and 83.6% respectively. Pharmacodynamic response (beta-blockade) was assessed by determining the degree of reduction of isoprenaline-induced tachycardia at different time intervals. A minimum concentration of 40-60 ng/ml drug in plasma was maintained during 1-10 h, and there has been a minimum of about 40-50% of beta-blockade during 1-9 h post administration. A good correlation between pharmacokinetic and pharmacodynamic profiles was observed. PMID- 8489558 TI - Cardiotonic activity of the water soluble forskolin derivative 8,13-epoxy-6 beta (piperidinoacetoxy)- 1 alpha, 7 beta, 9 alpha-trihydroxy-labd- 14en-11-one. AB - 8,13-Epoxy-6 beta-(piperidinoacetoxy)-1 alpha,7 beta, 9 alpha-trihydroxy-labd 14en-11-one (HL 706, CAS 114376-11-3) is a water soluble derivative of forskolin with positive inotropic and vasodilating properties. In both in vitro and in vivo preparations, it exhibited significant positive inotropic activity with concomitant increase in heart rate and decrease in mean blood pressure. Though its potency is lower than that of forskolin, its duration of action is more prolonged. In conscious dog experiments, HL 706, administered orally, also showed a dose related increase in LV dP/dtmax. A significant reversal of cardiac failure was attained in anaesthetised dogs subjected to propranolol induced cardiac insufficiency. HL 706, like forskolin increased cAMP by virtue of its adenylate cyclase stimulant activity. Through increase in cAMP it also exhibited non specific smooth muscle relaxant activity in isolated vascular and ileal preparations. Its therapeutic ratio is quite favourable. PMID- 8489560 TI - Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 1st Communication: balance of elimination, plasma and blood kinetics, metabolism in rats. AB - N-N'-Dicyclopropyl-methyl-piperazine-dichlorhydrate (Ino 2628-CZ) is a novel inotropic compound. The absorption, distribution, excretion and metabolism of radiochemically labelled 14C-Ino 2628-CZ has been studied in male and female rats after intravenous and oral administration. The compound was mainly excreted during the first 24 h after both administrations, although traces of radioactivity were still measured at 7 days post-dose. About 20% of the drug is excreted in the urine unchanged. Nine metabolites were separated, four of them being characterized. PMID- 8489561 TI - Stability of amiodarone in serum samples under various storage conditions. AB - The present study was intended to examine the stability of amiodarone (Cordarex, CAS 1951-25-3) and its metabolite desethylamiodarone. For this purpose 20 ml of blood were taken from each of 12 patients treated with amiodarone and were stored, after centrifuging, at room temperature, +5 degrees C, -18 degrees C and 38 degrees C. The amiodarone and desethylamiodarone concentrations were determined by the HPLC method 30 min, 24 h, 48 h, 72 h, one and two weeks after blood-taking. It turned out that the serum levels decreased continuously as of the first day regardless of the storage temperature. Correction factors were therefore calculated for the amiodarone concentration: if the blood level determination takes place after 24 h one should add 8% to the obtained value, after 48 h 16%, after 72 h 19%, after one week 23% and after two weeks 32%. PMID- 8489562 TI - Effect of naftidrofuryl on platelet-induced vasospasm in vitro. Role of antiserotonergic actions. AB - This study was designed to analyse the spasmolytic actions of naftidrofuryl (Dusodril, CAS 31329-57-4) more in detail, using isolated vessel segments of bovine coronary arteries (BCA). In this preparation, naftidrofuryl caused a dose dependent inhibition of 5-HT, U 46.619 ((5Z, 9a, 11a, 13E, 15S)-11,9 (epoxymethano) prosta-5,13-dienoic acid), PGF2 alpha and KCl-induced contractions. Additionally, the actions of naftidrofuryl on platelet-induced vasospasm were investigated using arachidonic acid (AA)-stimulated platelets and BCA. Naftidrofuryl antagonized the vasocontractile effects of secreted 5-HT, but was only slightly active in reducing the TXA2-dependent vessel contraction. The suppression of ADP-induced platelet aggregation and secretion required more than 300 mumol/l naftidrofuryl. These data support the concept of a spasmolytic activity of naftidrofuryl which also involves the antagonism of platelet-derived vasocontractile mediators. PMID- 8489563 TI - Time course of the anti-oedematous effect of different dose regimens of O-(beta hydroxyethyl) rutosides in healthy volunteers. AB - The aim of this study was to compare the efficacy of two posologies of hydroxyethylrutosides (HR) as maintenance dose for the reduction of leg oedema. The increase in leg volume induced by standing motionless for one hour was measured in 12 healthy young male volunteers by a highly sensitive water displacement method. The volume increase (approx. 87.8 units) was found to be very reproducible after a one-week placebo run-in period. The mean value after 3 weeks treatment at 1000 mg/day HR was reduced to 85.2 +/- 8.7 units. The subjects were then randomised to 3 groups and further measurements were made after additional 3, 5, 6 and 7 weeks. On placebo, the values returned to baseline within 5-6 weeks. On 500 mg/day, the values continued to oscillate around the values at randomisation (i.e., the effect was maintained). On continuing the dose unchanged at 1000 mg/day, the volume increases continued to fall progressively to 79.1 +/- 7.7 at the end of the further 7 weeks. After analysis of all mean volume changes relative to the values at time of randomisation, it was found that the 1000 mg/day dose showed a significant greater antioedematous effect than placebo (p = 0.0001) or 500 mg/day (p = 0.0028). Also the 500 mg/day dose was superior to placebo (p = 0.0328). We conclude that, after initial treatment for 3 weeks with 1000 mg/day, a dose of 500 mg/day is adequate to maintain the resultant anti oedematous effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489564 TI - Effect of acetyl-L-carnitine treatment on the levels of levocarnitine and its derivatives in streptozotocin-diabetic rats. AB - The effect of diabetes induced by streptozotocin and that of acetyl-L-carnitine (ALC) hydrochloride (CAS 5080-50-2) treatment on the homeostasis of the levocarnitine (L-carnitine) moiety was investigated in Sprague-Dawley rats. The diabetic status was ascertained by measuring blood glucose. L-carnitine (LC), total acid soluble L-carnitine (TC) and ALC were measured in serum, tissues and urine by radioenzymatic methods. Short-chain L-carnitine esters (SCLCE) were obtained by subtracting LC from TC. Serum concentration of L-carnitine moiety was decreased in diabetic when compared to normal rats; whereas ALC oral treatment (50 and 150 mg/kg p.o. for 4 weeks) in diabetic rats increased, dose-dependently, all the components of L-carnitine moiety, SCLCE and ALC being completely restored. In the liver of diabetic rats all the analytes proved to be higher than in normal rats, mainly LC and TC. A similar trend was observed in skeletal muscle, at least with LC and TC, whereas SCLCE and ALC were not affected. The treatment with ALC increased the liver concentration of all the analytes in a dose-related way whereas in skeletal muscle only LC and TC showed an increase with the highest dose of ALC. Myocardium and kidneys showed a decrease of all the analytes in diabetes; the treatment with ALC normalized the situation in kidneys, in a dose-related way, but not in the myocardium. Urinary excretion and renal clearance of L-carnitine moiety increased in diabetes; an additional dose-related increase was observed with the ALC treatment. PMID- 8489565 TI - Acetyl-L-carnitine effect on nerve conduction velocity in streptozotocin-diabetic rats. AB - Measurement of nerve conduction velocity (NCV) is a useful and sensitive tool for evaluating diabetes related neurological dysfunctions. The method used allows to monitor the parameter at different times in the same group of rats, so that it is possible to observe simultaneously the development of the damage in time, and to evaluate the improvement related to the treatment. The repeated oral treatment with acetyl-L-carnitine (ALC, CAS 5080-50-2) 250 mg/kg caused an improvement in NCV of the diabetic rats; the effect was higher when the treatment started early with respect to the diabetes induction. The improvement in NCV was constant in time and comparable from 2 to 6 weeks of the treatment. In conclusion, oral treatment with ALC was able to normalize the impairment of NCV in streptozotocin rats, the effect being constant in time from 2 to 6 weeks of treatment and up to 8 weeks after induction when administration started in early stage of diabetes (2 3 weeks after induction); however, at this time the NCV is already significantly decreased. PMID- 8489566 TI - [Comparison of the pharmacokinetics of a quick-release bezafibrate formulation with a sustained-release formulation. 1. Single-dose administration]. AB - Comparison of the Pharmacokinetic Profiles of a Quick and a Sustained Release Bezafibrate Formulation/1st Communication: Single-dose application The hypolipaemic agent bezafibrate (CAS 41859-67-0) is available as immediate and sustained release formulation. The pharmacokinetic profile of an immediate release 300 mg dragee (A) was compared in a two-way cross-over design to that of a 400 mg sustained release dragee (B). Neglecting the dose difference, the AUEC of A (28.8 micrograms/ml.h) was equal to that of B (27.6 micrograms/ml.h), whereas the bioavailability of A appeared to be higher than that of B when AUEC was corrected for dose (AUEC ratio = 137%). Regarding Cmax and tmax, both formulations exhibited the expected differences. PMID- 8489567 TI - [Comparison of the pharmacokinetics of a quick-release bezafibrate formulation with a sustained-release formulation. 2. Multiple-dose administration and chronopharmacokinetics]. AB - The pharmacokinetic profile of a 300 mg immediate release formulation (A) was compared to a 400 mg sustained release formulation (B) of the lipid lowering drug bezafibrate (CAS 41859-67-0). Preparation A was applied twice a day whereas B was applied once a day in the evening. The means of Cmax (12.5 micrograms/ml) and AUC (66.8 micrograms/ml.h) for preparation A were considerably higher than for B (Cmax: 6.6 micrograms/ml, AUC: 39.8 micrograms/ml.h), whereas no differences were found regarding Tcav (A: 8.9 h, B: 8.3 h) and PTF (A: 4.6, B; 4.1). An AUC ratio for A/B of 119% (CI90%: 108-132%) was determined after dose correction. For A an AUC/AUEC ratio of 110% was found when comparing multiple versus single-dose application, whereas this ratio with 136% appeared to be considerably higher for B. Slight chronopharmacological effects were found for preparation A, which was applied twice a day in the evening and in the morning. During night-time the AUC was (insignificantly) 12% higher than during day-time, whereas the apparent elimination halflife time was 40% longer at night (p < 0.025), which corresponded to an extended tmax of median 3 h during night-time as compared to 1.75 h at day time. PMID- 8489568 TI - Structural characterization of terflavoxate. AB - Data are reported on the structural characterization of 3-methyl-4-oxo-2-phenyl 4H-1-benzopyran-8-carboxylic acid 1,1-dimethyl-2-(N-piperidinyl)ethyl ester hydrochloride (terflavoxate-HCl, Rec 15/2053, CAS 86433-39-8), a new antispasmodic for the lower urinary tract. UV, IR, NMR and MS spectra fully confirmed the structure. The X-ray crystal structure determination revealed that the molecular structure consists of a rigid platform, formed by the chromone system, with two arms, the phenyl group at C(2) and the ester chain at C(8). The ester chain conformation generates a small hollow where two oxygen atoms face. PMID- 8489569 TI - Pharmacokinetic studies in healthy volunteers on a new gastroprotective pharmaceutic form of diclofenac. AB - The pharmacokinetic properties of a new gastroprotective pharmaceutical formulation of diclofenac (CAS 15307-79-6) were investigated in twelve healthy volunteers. In this new form the diclofenac is the nucleus of sequential sucralfate-covered tablets. The experimental design was an open, random, two period balanced cross-over study. All the subjects received a single oral dose of 50 mg diclofenac contained in the new formulation or in the reference enteric coated tablets. Plasma concentrations of diclofenac were determined at 0.5, 1, 2, 4, 6, and 8 h after drug administration using HPLC method. After administration of a diclofenac-sucralfate association diclofenac was quickly absorbed and the peak plasma concentration (0.773 +/- 0.08 microgram/ml) was achieved in about 1 h. AUC(0-infinity) value was about 1.8 micrograms/ml/h and the mean elimination half-life was 1.20 +/- 0.12 h. The pharmacokinetic profile of diclofenac sucralfate association is similar to the values reported in previous papers for enteric-coated forms; anyway an early occurrence of the peak plasma concentration was observed for the new formulation. The new diclofenac-sucralfate association shows a different rate of absorption (namely an early and greater peak plasma concentration of diclofenac) and a similar extent of absorption (AUC(0-infinity) being not statistically different) as compared to the reference enteric-coated tablets of 50 mg diclofenac. These results could be related to the delaying and protective effect of sucralfate whose action is different from the one carried by the coat of the enteric-coated tablets. PMID- 8489570 TI - Intracellular changes of HeLa cells after single or repeated treatment with cytostatics. AB - HeLa cells were treated once or repeatedly using the cytostatics doxorubicin (adriamycin, Ad, CAS 23214-92-8), cisplatin (Pt, CAS 15663-27-1) and fluorouracil (FU, CAS 51-21-8). Intracellular GSH (reduced glutathione) contents, activities of protein kinase C, cytotoxicity and membrane fluidity were investigated. During single treatment protein kinase C activities as well as membrane fluidity increased, whereas intracellular GSH decreased. With repeated treatments protein kinase C activities increased further. Membrane fluidity as well as intracellular GSH contents increased. The investigated parameters may be correlated with sensitivity of cells against cytostatics. PMID- 8489571 TI - In vitro cytotoxic activity of an N-hydroxypyridine-2-thione derivative. AB - The in vitro antitumor activity of N-(1-adamantoyloxy)pyridine-2-thione (APT), an N-hydroxypyridine-2-thione derivative, was investigated against a panel of both murine and human tumor cell lines growing in vitro. To evaluate the cytotoxic activity of APT the MTT ((4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) in vitro assay was used, which is considered to have predictive value for drug chemosensitivity evaluation. The results demonstrate that APT has antitumor activity, thus confirming theoretical suppositions about its cytoreductive potential. PMID- 8489572 TI - Pharmacokinetics and tolerance of fluconazole suppositories in healthy volunteers. AB - Fluconazole (Diflucan, CAS 86386-73-4) suppositories offer a novel way to administer this systemically active antimycotic. The pharmacokinetics and toleration of this new formulation have now been examined in healthy adult volunteers. In crossover experiments the bioequivalence was demonstrated for 200 mg suppositories and 200 mg capsules, and for 25 mg suppositories and 25 mg fluconazole in an oral suspension. The mean bioavailability of the 200 mg suppository relative to the capsule was about 93%. The mean bioavailability of the 25 mg suppository relative to the oral suspension was 107%. Absorption of fluconazole after administration of the suppositories was, however, somewhat slower than after oral ingestion of the capsule or suspension. The pharmacokinetic parameters of the 200 mg and 25 mg suppositories suggest that the kinetics of rectally administered fluconazole are linear with dosage. Daily administration of the 200 mg suppository gives a continuous increase in the mean fluconazole plasma concentration, until steady-state is reached on about the 5th day. The systemic and local toleration of the fluconazole suppositories was good. PMID- 8489573 TI - Effects of D-penicillamine on human cell lines. AB - The effect of penicillamine on the proliferation and viability of human T, B and premacrophage/promyelocytic cell lines was evaluated. Whereas Raji cells and U937 cells were not negatively influenced by the addition of 0.03-0.97 mmol/l D penicillamine (D-Pen, Trolovol, CAS 52-67-5), other cell lines such as H9, NC37 and HL60 were clearly impaired by concentrations between 0.12 and 0.49 mmol/l. Similar effects on the uptake of 3H-thymidine, 3H-uridine and 3H-leucine were observed with the addition of other stereoisomeric forms of penicillamine, D,L- and L-penicillamine to H9 cell cultures. The evaluation of cell number and viability by light microscopy revealed similar actions of penicillamine on cell cultures. By these means its repressing effect on Jurkat, NC37 and even on U937 became more transparent. PMID- 8489574 TI - Pen-based remote data entry system. A pilot clinical trial. AB - This study assesses the feasibility of pen-based remote data entry and measures the acceptance of such systems by patients and physicians. Three clinical investigators participated in a phase-I/II clinical trial of escalated doses of chemotherapy followed by Granulocyte-Macrophage Colony-Stimulating Factor (GM CSF). The study included 20 patients with testicular cancer who were treated at three university hospitals. The patients' data obtained in this trial were recorded and stored on a pen-based computer system. A total of 798 data points were recorded for each patient using 33 electronic forms resembling the paper forms used during an earlier phase of the study. The data recorded include the past medical history, inclusion/exclusion criteria, disease staging, therapy documentation, laboratory values and side effects. Both physicians and patients were interviewed directly after using the pen-based remote data entry system. Patients accepted that their physician was taking notes on an electronic form rather than on paper. All patients noted that a pen-based system is superior to a desktop computer when used during an interview. For the investigators electronic data entry takes additional effort, but time savings are realized later with less data clearing and increased data quality. These benefits are important for the study sponsor as well. In conclusion, pen-based remote data entry is a feasible new mode of recording clinical data with concrete benefits to both investigators and sponsors. PMID- 8489575 TI - Mifepristone (RU 486)--an abortifacient to prevent abortion? PMID- 8489576 TI - How to diagnose and treat Lyme disease in children. PMID- 8489577 TI - Do medical journals suppress information? PMID- 8489578 TI - Oxygen content, blood viscosity, and cerebral blood flow. PMID- 8489579 TI - Relation of site of acute myocardial infarction to the site of maximal coronary narrowing. PMID- 8489580 TI - Statistical problems with small sample size. PMID- 8489581 TI - Temperature monitoring during radiofrequency catheter ablation. PMID- 8489582 TI - Obstruction in chronic pancreatitis. PMID- 8489583 TI - The MD thesis in the training of a consultant physician. PMID- 8489584 TI - Quality of care in rural hospitals. PMID- 8489585 TI - Heterosexual transmission of HIV. PMID- 8489586 TI - Radiotherapy plus chemotherapy for head and neck cancer. PMID- 8489587 TI - More on disclosure of AIDS in celebrities. PMID- 8489588 TI - Aseptic meningitis and intravenous gammaglobulin treatment. PMID- 8489589 TI - A more specific definition of pathology practice. PMID- 8489590 TI - Renal failure after eating "magic" mushrooms. PMID- 8489591 TI - Normal concentration of uranium in urine. PMID- 8489592 TI - Medical waste. PMID- 8489593 TI - Pulmonary embolism caused by venous compression ultrasound examination. PMID- 8489594 TI - Sensitivity of ocular pulse amplitude. PMID- 8489595 TI - Response to editorial on obstetric anesthesia. PMID- 8489596 TI - Using music therapy as distraction during lumbar punctures. PMID- 8489597 TI - Doppler ultrasound and the silent ductus arteriosus. PMID- 8489598 TI - Blood loss during total hip replacement. PMID- 8489599 TI - Face masks and spinal anaesthesia. PMID- 8489600 TI - Misuse of anabolic drugs. PMID- 8489601 TI - Misuse of anabolic drugs. PMID- 8489602 TI - Asking patients about their treatment. PMID- 8489603 TI - Medical education. PMID- 8489604 TI - Practice reports. PMID- 8489605 TI - Consultant episodes. PMID- 8489606 TI - . . . and the value of membership for all. PMID- 8489607 TI - Combination treatment of depression. PMID- 8489608 TI - Conversion mnemonic. PMID- 8489609 TI - 'Mabi bark tea' consumption and psychosis? PMID- 8489610 TI - Endocrine findings in Cushing's disease. PMID- 8489611 TI - The cranial base in subjects with dental and skeletal Class II. PMID- 8489612 TI - Leiomyosarcoma with osteoclast-like giant cells. PMID- 8489613 TI - Subcutaneous T-cell lymphoma with florid granulomatous panniculitis. PMID- 8489614 TI - Hospitals without walls. PMID- 8489615 TI - The radiobiology of radiosurgery. PMID- 8489616 TI - "Does Kentucky need a primary medical school?". PMID- 8489617 TI - Cholesterol and mortality. PMID- 8489618 TI - In-house trauma surgeon--paradigm or paradox. PMID- 8489619 TI - 98.6 degrees F. PMID- 8489620 TI - 98.6 degrees F. PMID- 8489621 TI - Evaluation of a breast mass. PMID- 8489622 TI - Early single-stage repair of complex craniofacial trauma. PMID- 8489623 TI - Pontine hemorrhage. PMID- 8489624 TI - MS and Sjogren's syndrome. PMID- 8489625 TI - Natural oocyte retrieval with intravaginal fertilization: a simplified approach to in vitro fertilization. PMID- 8489626 TI - Hemolytic disease of the fetus: a plea for restraint. PMID- 8489627 TI - HMG CoA reductase inhibitors and diet in familial hypercholesterolaemia. PMID- 8489628 TI - Intravenous drips. PMID- 8489629 TI - Casualty slaughter prosecution. PMID- 8489630 TI - Is a casualty slaughter service necessary? PMID- 8489631 TI - Perilous times in pathology education. PMID- 8489632 TI - Methadone maintenance and recovery. PMID- 8489633 TI - Incidental appendectomy and pathologic conditions of the appendix vermiformis. PMID- 8489634 TI - The bigger slice of the pie? PMID- 8489635 TI - Measles and low serum vitamin A values. PMID- 8489636 TI - Treatment of lymphoid interstitial pneumonia with chloroquine. PMID- 8489637 TI - Ankylosing spondylitis with exuberant sclerosis or SAPHO syndrome? PMID- 8489638 TI - Variability in bone mass measurement. PMID- 8489639 TI - Pectus excavatum. PMID- 8489641 TI - Bovine caesarean section. PMID- 8489640 TI - Saddened not amused. PMID- 8489642 TI - Effects of thiazide diuretic therapy on bone mass, fractures, and falls. The Study of Osteoporotic Fractures Research Group. AB - OBJECTIVE: To determine the relation between the use of thiazide diuretics and bone mass, fractures, and falls in older women. DESIGN: Cross-sectional study of thiazide diuretics, bone mass, and prevalent vertebral deformities; cohort analysis of thiazide diuretics and nonspinal fractures and falls. SETTING: Four clinical centers located in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: A total of 9704 ambulatory, nonblack women who were 65 years or older. MEASUREMENTS: Information on thiazide use, demographic data, medical history, and anthropometric measurements were obtained by questionnaire, interview, and examination. Appendicular bone mass was measured by single-photon absorptiometry. Incident falls and fractures were ascertained every 4 months. RESULTS: Women using thiazide diuretics for more than 10 years had significantly higher bone mass than women who had never used thiazide diuretics (for example, 0.381 g/cm2 compared with 0.355 g/cm2 for the distal radius [P < 0.001]). Current users of thiazide diuretics had an incidence of falls (relative risk, 1.06; 95% CI, 0.90 to 1.25) that was similar to that of those who had never used these drugs. After adjusting for age, body weight, functional status, total calcium intake, duration of estrogen replacement therapy, and self-reported health status, we found that current users of thiazide diuretics who had taken these drugs for more than 10 years had a risk for nonspinal (relative risk, 0.99; CI, 0.81 to 1.20) and osteoporotic (relative risk, 0.98; CI, 0.79 to 1.22) fractures that was similar to that of women who had never used thiazides; however, thiazide users did have a lower risk for fractures of the hip (relative risk, 0.63; CI, 0.34 to 1.16) and wrist (relative risk, 0.66; CI, 0.40 to 1.08), neither of which was significant. CONCLUSIONS: Thiazide diuretics have no effect on a women's risk for falling or for experiencing nonspinal fractures. The trend toward a lower risk for hip and wrist fractures is consistent with findings in previous cohort studies but may reflect selection factors for the use of thiazide diuretics. A randomized trial is needed to determine the effect ot thiazide diuretics on the incidence of fractures. PMID- 8489643 TI - Increased human erythrocyte sodium-lithium countertransport in hyperlipidaemic patients may indicate increased membrane lipid fluidity. AB - Erythrocyte sodium-lithium countertransport (SLC) activity, membrane fluidity, plasma triglyceride and cholesterol were measured in hyperlipidaemic patients and normal subjects. Fluidity was assessed by the fluorescence anisotropy (inversely related to fluidity) of the probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,4 trimethylammonium-3,5-hexatriene (TMA-DPH). In a second group of patients the maximum velocity (Vmax) and external sodium affinity constant (km) of SLC was also measured. In the first group of patients, SLC activity was increased compared with the controls (0.279 +/- 0.019 vs. 0.213 +/- 0.013, P = 0.006) as was membrane fluidity in the deep hydrophobic regions (DPH anisotropy 0.211 +/- 0.0007 vs. 0.215 +/- 0.0011, P = 0.007). There was a strong correlation between SLC and DPH anisotropy (Rs = -0.72, P = < 0.001) which was due to the correlation between Vmax and DPH anisotropy (Rs = -0.90, P = < 0.001). Increases in Vmax of SLC in hyperlipidaemic patients may be due to differences in lipid organisation in the deep hydrophobic regions of the membrane which may affect the turnover rate of the transporter. PMID- 8489644 TI - Lyme disease. A Canadian perspective. AB - Lyme disease is an expanding community health issue in the United States. This has led to greater public awareness in Canada, although the disease remains rare here. We review the biology of ticks and show how feeding patterns are relevant to disease transmission. Diagnosing Lyme disease is sometimes problematic, but treatment can be effective, particularly in the early stages. Preventive measures are aimed at avoiding tick contact and early tick removal. PMID- 8489645 TI - [Gastric adenocarcinoma with an endocrine component. Report of nine cases]. AB - Nine gastric adenocarcinomas containing endocrine cells were retrospectively studied to evaluate anatomo-clinical and immunohistochemical features, and the out-come of the patients. These gastric tumors were bulky with frequently lymph node metastasis. The immunohistochemical analysis had shown that all tumors contain EC cells, two tumors D cells, one tumor PP cells, but neither G cells nor A cells were detected. Five-years survival rate of these gastric tumors was slightly but not significantly increased as compared to usual adenocarcinomas (45.5% vs 36.5%). However, one can raise the question of possible control of local hormonal secretions on tumoral growth, particularly the anti-trophic part of the somatostatin. PMID- 8489646 TI - [Hepatic epithelioid hemangioendothelioma. A case with liver transplantation. Review of the literature]. AB - Epithelioid hemangioendothelioma (HEE) is an unusual malignant neoplasm of vasculo-endothelial origin, arising in soft tissues, lung and liver. One case of hepatic HEE is reported in a 32 year-old man wit an isolated multinodular hepatomegaly. The diagnosis was made by the histologic examination of biopsy specimens. At the time of diagnosis, there was evidence of pulmonary metastasis. However, an orthotopic liver transplantation was performed. The tumor cells were immunoreactive with factor VIII-related antigen, BNH9 and vimentin. There was no expression of cytokeratin and epithelial membrane antigen. The patient is alive and well 24 months after. The thoracic X-ray are unchanged. This case is compared with the 84 others cases of the literature. Fourteen experienced a favorable outcome after transplantation. Extra-hepatic dissemination doesn't contra indicate the graft. But hilar vascular involvement may be correlated with worse prognosis. PMID- 8489647 TI - [Follicular mucinosis. A dermatologic disorder frequently associated with T-cell lymphoma]. AB - The case of a 40-year-old man with follicular mucinosis and simultaneous cutaneous T-cell lymphoma is reported. This observation emphasizes 1) the difficulties to interpret the lymphoid infiltration which accompanies a follicular mucinosis, 2) the necessity of immunochemistry and multiple biopsies in order not to ignore an associated lymphoma. PMID- 8489648 TI - [Inflammatory pseudo-tumor of the lung. Clinico-pathologic report of a case]. AB - One case of a solitary pulmonary nodule occurring in a 54-year-old woman with history of breast carcinoma is presented. Histological examination of the surgical specimen excluded breast carcinoma metastasis and revealed an inflammatory pseudotumor. Principal clinico-pathological findings in previously reported cases are described. Inflammatory pseudotumors may exhibit, as in our case, some nuclear atypia making the diagnosis sometimes difficult with malignancy. PMID- 8489649 TI - [Botryoid rhabdomyosarcoma of the cervix. Clinico-pathologic study of a case]. AB - The botryoid rhabdomyosarcoma of the cervix is a rare tumour occurring in young woman or during genital activity. It mainly causes vaginal bleeding or appears as a polypoid grape-like mass with a gelatinous cut-surface. The diagnosis is based on the presence of a submucosal cambium layer and a rhabdomyoblastic differentiation, corresponding to an intracytoplasmic double cross-striation. Metaplastic cartilaginous islands are sometimes observed. The immunostaining ensures the muscular origin of the tumour, characterized by the expression of actin and desmin. Apart from mullerian adenosarcomas, the main differential diagnosis is represented by the benign polypoid formations of the cervix: the genital rhabdomyoma and the fibroblastic lesion, called fibro-epithelial polyp with atypical stroma. The treatment actually includes both chemotherapy and surgery which is often limited to a conization. PMID- 8489650 TI - [Specimen fixation in seminoma]. PMID- 8489651 TI - [Vaginal polyp. Case for diagnosis]. PMID- 8489653 TI - [VIIth Meeting on Research in Cellular Pathology. Paris, 9 December 1992. Abstracts]. PMID- 8489652 TI - [Invisible dermatoses]. PMID- 8489654 TI - ["Bronchiolitis obliterans"]. PMID- 8489655 TI - [Lung rejection in pulmonary and cardiopulmonary transplantation]. PMID- 8489656 TI - The use of intravenous ketorolac for the treatment of renal colic in the emergency department. AB - The objective of this study was to report the authors' experience using intravenous ketorolac (Syntex Laboratories, Palo Alto, CA) as an analgesic in the treatment of renal colic in a convenience sample at three suburban community hospital emergency departments. Twenty-five patients with renal colic were participants. Pregnant women, patients with a history of renal or hepatic impairment, bleeding diathesis, active peptic ulcer disease, or hypersensitivity to aspirin or nonsteroidal antiinflammatory drugs (NSAID) were excluded. Ketorolac 30 mg administered intravenously during a 1-minute period, and the following parameters were monitored at times 0, 5, 10, 20, 30, and 60 minutes: pain on a scale of 0 to 10, pulse rate, blood pressure, and adverse side effects. A total of 25 patients were included in our series. Initially, they had a median pain score of 9 with an interquartile range of 1. Thereafter, the median pain scores and (interquartile ranges) were 8 (three) at 5 minutes, 5 (four) at 10 minutes, 2 (four) at 20 minutes, 1 (three) at 30 minutes, and 0 (one) at 60 minutes. There were no adverse side effects observed in any patients. Therefore, it can be concluded that intravenous ketorolac is an effective analgesic agent for the control of pain in patients with renal colic. PMID- 8489657 TI - Survival from out-of-hospital cardiac arrest: effects of patient age and presence of 911 Emergency Medical Services phone access. AB - The purpose of this investigation was to determine factors associated with survival from out-of-hospital cardiac arrest, including effects of 911 Emergency Medical Services telephone access and the age of patient. Subjects included 1,753 prehospital cardiac arrest patients in Iowa. Patient survival status and other variables were compared for patients with access to a 911 service with those who did not, and for different age categories, using univariate associations and multivariate logistic regression analysis. The presence of 911 telephone access was significantly associated with survival from out-of-hospital cardiac arrest (9.18% versus 5.35% survival for 911 versus no 911 groups, respectively). This association was partially the result of the significant association of 911 with decreased time from collapse to call for help, decreased time to cardiopulmonary resuscitation (CPR), and decreased time to first shock (if in ventricular fibrillation [VF]). Younger age was significantly associated with survival in univariate analyses (8.94% versus 6.26% survival for younger versus older age groups, respectively), but this was not an independent association, which is indicated by the lack of significance of age in the multivariate model. PMID- 8489658 TI - Cricothyrotomy performed by prehospital personnel: a comparison of two techniques in a human cadaver model. AB - Little is known about the proficiency of prehospital personnel when performing cricothyrotomies. The authors compared two techniques for establishing an airway through the cricothyroid membrane used by paramedic students. One technique used a prepackaged kit that consisted of a dilator that is passed percutaneously through a breakaway needle. This percutaneous device (PD) was compared with a standard surgical approach (SA) using a scalpel and endotracheal tube. Data was collected on a total of 44 paramedic students who were allowed to attempt each of the procedures. No significant difference in the success rate on the first attempt was found between the two procedures (86% for the SA and 73% for the PD; P = .186). The surgical approach was significantly faster (46 +/- 17 seconds v 103 +/- 62 seconds; P < .01). It was also judged to be significantly easier to perform when evaluated on a linear analog scale (SA, 2.6 +/- 2.0 v PD, 5.1 +/- 2.8; P < .001). Because some procedures were performed on cadavers whose cricothyroid membranes had already been violated, the procedures performed on intact membranes only were also analyzed. Similar, statistically significant differences for insertion time and ease of insertion were again found. Prehospital personnel can be trained to perform cricothyrotomies with a reasonable degree of proficiency. A traditional surgical approach, however, may be faster and less difficult to perform than a comparable procedure using a commercially available percutaneous device. PMID- 8489659 TI - Prehospital seizure management: triage criteria for the advanced life support rescue team. AB - The present study was completed to establish advanced life support (ALS) versus non-ALS triage criteria for use by ALS prehospital personnel when faced with the seizure patient, in the hope of more efficient use of ALS rescue teams. Preselected triage criteria for acuity of care based on neurological condition, vital signs, and concomitant illness/injury were tested against retrospective data (paramedic run reports) collected on 230 patients. Triage criteria sensitivity (SENS), specificity (SPEC), positive predictive value (PPV), and negative predictive value (NPV) were determined with a 95% confidence interval (CI). Point estimate of use/need of care was noted. ALS interventions were instituted in 58 patients (25%). In 57 of these cases, indication for and ALS intervention, were established on initial patient assessment (SENS, 98.28; 95% CI, 90.76 to 99.96). Of 173 patients requiring no ALS intervention on initial assessment, only 1 (0.58%) developed complications warranting ALS therapy during the course of prehospital care (SPEC, 100.00; 95% CI, 100.00 to 99.99; PPV, 100.00; 95% CI, 100.00 to 94.63; NPV, 99.42; 95% CI, 96.82 to 99.99). No inappropriate use, point estimate (PE) [(0)/(172) (0.00% to 0.01%)] or unmet need, PE [(0)/(58) (0.00% to 5.16%)] of care was noted. The data presented in this study suggest that given similar field times, after initial patient assessment by ALS personnel, it is reasonable and safe to triage seizure patients who do not require ALS intervention to non-ALS rescue teams for continuation of care and transportation. PMID- 8489661 TI - Incidence of urethral disruption in females with traumatic pelvic fractures. AB - According to the National Center for Health Statistics, in 1986 1.4 million female patients in the United States were admitted to inpatient and short-stay nonfederal hospitals as a result of injuries acquired secondary to trauma. Of these, 45,000 had traumatic pelvic fractures. Rupture of the urethra is the most important lower urinary tract injury associated with traumatic pelvic fracture because of the high incidence of serious complications, such as urethral stricture and incontinence. To our knowledge, there are no satisfactory studies in the English literature documenting the incidence of urethral disruption in females with traumatic pelvic fractures. The records of all women patients with pelvic fractures registered in the Latter Day Saints Hospital trauma registry between July 1, 1981 and August 31, 1987 were reviewed. Of 146 female patients with traumatic pelvic fractures who were hospitalized during this period, none was found to have an urethral injury. Two patients (1.4%) had bladder contusions, and one (.7%) had a bladder rupture. This was the first large series attempting to identify the true incidence of urethral disruption in females with traumatic pelvic fracture, and it was found to be a rare occurrence. PMID- 8489660 TI - Changes in the parameters of oxygen metabolism in a clinical course recovering from potassium cyanide. AB - Poisoning with potassium cyanide is usually fatal because of the inhibition of cytochrome oxidase. The parameters of oxygen metabolism in a patient with cyanide poisoning who was admitted in a coma with seizures was monitored. The administration of amyl nitrite and sodium thiosulfate led to a rapid improvement: the parameters reflecting oxygen metabolism improved and the plasma level of cyanide decreased. The patient revived 1 1/2 hours after treatment. The arterial ketone body ratio (AKBR), which is the ratio of acetoacetate to beta hydroxybutyrate in arterial blood and which reflects the redox state in liver mitochondria, improved dramatically following treatment. Because the AKBR changes in relation to electron transport in liver mitochondria, it seems to be a logical parameter for evaluating the effect of potassium cyanide poisoning on electron transport. The AKBR also reflects the efficacy of treatment for cyanide poisoning. PMID- 8489662 TI - Out-of-hospital resuscitation preferences of emergency health care workers. AB - The objective of this study was to assess the personal preferences of emergency physicians, nurses, and medical technicians regarding their own potential out-of hospital resuscitation. An anonymous multiitem survey instrument was used at a statewide emergency medicine educational conference. Emergency personnel who regularly treat out-of-hospital cardiac arrest patients were enlisted to participate. Subjects picked the last intervention that they would wish for themselves in an optimally managed advanced cardiac life support (ACLS)-based resuscitation for ventricular fibrillation. One hundred millimeter visual analog scales were used to measure individual preferences for severe neurological disability or death. Hypothesis testing was by analysis of variance with Newman Keuls, multiple regression with stepwise variable selection, and the chi 2 and binomial distributions. Of 185 survey instruments, 105 were returned completed by eligible subjects. There was little difference among the three occupational groups (P > .5), although older respondents favored shorter resuscitations (r = .38; P = .002). Ten subjects did not want cardiopulmonary resuscitation started, and 65% wanted resuscitation stopped before the second dose of epinephrine. Only three subjects chose to undergo the entire ACLS sequence. Eighty-two percent of respondents preferred death to severe neurological disability. Emergency health care professionals have a unique personal awareness of issues surrounding out-of hospital resuscitation. That a large majority would prefer death to severe disability and few would willingly undergo full resuscitation as currently practiced suggests that prevailing guidelines should be reevaluated. PMID- 8489663 TI - Counseling parents of a child dead on arrival: a survey of emergency departments. AB - The purposes of this study were to (1) document whether or not responding emergency departments (EDs) have a process and/or team to interact with parents of children dead on arrival (DOA); (2) conduct a needs assessment to determine what information is essential to convey to a family of a child DOA; and (3) determine what EDs are doing to their residents/fellows in crisis counseling. A survey instrument was developed using input from key health care professionals at Children's Hospital who are involved in the acute care of children and their families. This survey was sent to directors of EDs in all children's hospitals and those general hospitals with more than 400 beds. Respondents identified themselves as ED directors at children's hospitals or general hospitals throughout the United States. The survey documented the lack of a process or team approach to counseling the family of a child who presents DOA. Often, the most inexperienced physicians are expected to provide this information and to counsel parents. Few EDs reported offering communication skills training in this area. Many respondents expressed dissatisfaction about the lack of a process or team regarding patients who present DOA and recognize the need for improvement. PMID- 8489664 TI - Acute pancreatitis related to anticardiolipin antibodies in lupus patients visiting an emergency department. AB - Four patients with systemic lupus erythematosus visiting an emergency department were reported with clinical presentation of acute pancreatitis. All had high levels of anticardiolipin antibodies (aCL); at autopsy, one had multiple thrombi within the blood vessels of the pancreas. The aCL antibody might play an important role in the pathogenesis of acute pancreatitis. Three patients had multiple organ involvement, especially the central nervous system, concomitant with an acute attack of pancreatitis; all died from these complications. Thus it was suggested that initial acute pancreatitis is an omnious prognostic factor in lupus patients visiting an emergency department. When evaluating lupus patients visiting an emergency department, clinicians should be alert to the status of aCL and the possibility of pancreatitis in these patients. PMID- 8489665 TI - Atypical ectopic pregnancy. AB - Most emergency physicians will agree that bleeding and abdominal pain in women of child-bearing age is considered an ectopic pregnancy until proven otherwise. Ectopic pregnancy remains the leading cause of maternal mortality in the United States. A high index of suspicion is necessary for early intervention and reduction in morbidity and mortality. Risk factors for ectopic pregnancy include previous salpingo-oophoritis, ectopic pregnancy, tubal surgery or ligation, use of an intrauterine device, hormonal therapy, and, more recently, in vitro fertilization. In addition, this case emphasizes the possibility of ectopic pregnancy in women with a history of hysterectomy without bilateral oophorectomy. PMID- 8489666 TI - Isolated sphenoid sinusitis. AB - Isolated sphenoid sinusitis is an uncommon but potentially catastrophic infectious disease. The authors present 12 patients with acute, isolated sphenoid sinusitis and describe their presenting features and clinical courses. All patients experienced headache, facial pain, or both. Fever and leukocytosis were uncommon. Plain sinus radiographs and cranial computerized tomography scan were diagnostic. All patients were treated with antibiotics and recovered without infectious or neurological complications. PMID- 8489667 TI - Streptococcal toxic shock-like syndrome presenting with hypoglycemia and reversible paralysis. AB - A patient with pharyngitis progressive to Toxic Shock-Like Syndrome presented to the emergency department with a chief complaint of lower extremity paralysis. This paraplegia was completely reversed with the administration of intravenous glucose. Hypoglycemia-induced paraplegia has not previously been reported in the medical literature, and this report emphasizes the importance of considering low blood glucose as a potential etiology for patients who present with these neurological symptoms. PMID- 8489668 TI - Lidocaine in refractory status epilepticus: a forgotten drug in the emergency department. AB - Generalized tonic-clonic status epilepticus is usually treated with intravenous benzodiazepines and phenytoin. Patients who do not respond to this treatment are generally treated with phenobarbital or general anesthetics both of which may require intubation to maintain respiration. Our experience of four cases with status epilepticus treated with intravenous lidocaine who had failed to respond to diazepam and phenytoin therapy is presented. Two cases responded to a single dose of lidocaine, one required a second dose of lidocaine to control seizures, and the fourth patient failed to respond and died as a result of associated severe head injury. Therefore, there is a need to conduct further studies to establish the efficacy of intravenous lidocaine in the treatment of refractory status epilepticus. PMID- 8489669 TI - Acceleration of the ventricular response in paroxysmal lone atrial fibrillation following the injection of adenosine. AB - Treatment of a patient with new onset atrial fibrillation with intravenous adenosine was followed by transient but significant acceleration of the ventricular rate. This unexpected response to adenosine can be explained by a predominating increase in sympathetic discharge relative to the drug's direct atrial ventricular nodal-blocking action. PMID- 8489670 TI - Pediatric acepromazine poisoning: the importance of child-resistant packaging for veterinary drugs. AB - The first reported case of acepromazine ingestion in a pediatric patient is presented. It is an aliphatic phenothiazine that is structurally similar to chlorpromazine (thorazine). In our case, a 2 1/2-year-old male ingested 3 to 4 of his 80-pound Doberman's 25-mg tablets. The pills were stored in a vial without a child-resistant closure. The child displayed signs and symptoms of phenothiazine toxicity. There is no federal law which requires veterinary medicines to be dispensed in special packaging. All prescription medications should require child resistant packaging. PMID- 8489671 TI - Respiratory failure following adenosine administration. AB - Adenosine is frequently administered to convert the rhythm of patients with paroxysmal supraventricular tachycardia to sinus rhythm. Adverse reactions are common after its administration, but these have been short-lived because adenosine has a half-life of less than 10 seconds. This report describes a 54 year-old male patient with chronic obstructive pulmonary disease who presented with paroxysmal supraventricular tachycardia at 200 beats/min. A 12-mg bolus injection of adenosine aggravated mild bronchospasm and produced respiratory failure. The patient subsequently required ventilatory support for 9 days. The presence of bronchoconstriction should be considered as a possible contraindication to the administration of intravenous adenosine. PMID- 8489672 TI - Increases in serum prolactin levels associated with syncopal attacks. AB - Numerous investigators have found that serum prolactin levels increase after tonic-clonic and partial complex seizures, but the effect of syncope on prolactin levels has been studied little. Serum prolactin levels were measured following unexpected syncopal attacks in patients seeking emergency treatment in a community hospital. Levels sampled 18 to 60 minutes after syncopal episodes were increased in 8 of 11 cases. Follow-up prolactin levels, measured 17 to 222 days later, were normal in all eight cases in which they were initially increased. Most subjects had concurrent illness. Although the current study does not clarify whether it was the syncope, the concurrent illness, or both that caused the prolactin elevations, it implies that measurement of this hormone will not help the clinician in distinguishing between seizures and syncopal attacks. PMID- 8489673 TI - Symptomatic bradycardia following the administration of sublingual nitroglycerin. AB - A case of severe bradycardia with junctional escape immediately following sublingual nitroglycerin is described. Bradycardia is a rare, but well documented, complication of nitroglycerin and is often reported in the setting of myocardial ischemia or infarction. This particular case reported was complicated by the presence of an angiographically documented congenital coronary anomaly, but did not have either electrocardiographic or enzymatic evidence of ischemia or infarction during this event. Previously reported cases were reviewed, as well as potential mechanisms for this phenomenon. All cases reported to date were easily corrected with passive leg elevation or atropine. PMID- 8489674 TI - Cervical spine trauma in children: Part II. Mechanisms and manifestations of injury, therapeutic considerations. PMID- 8489675 TI - Human rabies: a review. AB - Human rabies is a rarely observed but frequently prophylaxed disease in North America. Presented in this review is a typical emergency department case and a summary of the epidemiology of the rabies virus, its clinical appearances, diagnosis, and management. Emphasis is placed on issues pertinent to the emergency physician practicing in the United States. Current recommendations for the administration of both active and passive immunotherapy for preexposure and postexposure prophylaxis are discussed. A treatment algorithm to aid in the decisions faced by a practicing physician regarding proper animal management and patient therapy and future prospects for the control of rabies in wild animal populations are also included. PMID- 8489676 TI - Cases in electrocardiography. PMID- 8489677 TI - Discrepancy in resuscitation beliefs among physicians at various levels of training. AB - Having previously described some of the attitudes of health care providers toward resuscitation for themselves, based on an individual's beliefs about the likelihood of success of cardiopulmonary resuscitation (CPR), the differences among attitudes of physicians at different levels of training have now been assessed. A multi-question survey was sent to medical students, house officers, and attending physicians at two university medical centers. Sociodemographic information, questions regarding beliefs about outcome after CPR, and personal desires were included. Respondents were asked to identify the clinical condition carrying the worst prognosis during cardiac arrest from among: metastatic cancer (MC), end-stage renal disease (ESRD), acquired immunodeficiency syndrome (AIDS), sepsis, and myocardial infarction (MI), and to specify their resuscitation desires should they be affected by these conditions. The preferences of each group regarding resuscitation given their least favored diagnosis were assessed using chi 2 analysis of trends for binomial proportions. Approximately 186 questionnaires were evaluated and consisted of 90 by medical students (MS), 67 by house officers (HOs), and 29 by attending physicians (APs). Resuscitation desires for each diagnosis were MC, 7 of 40; ESRD, 8 of 34; AIDS, 10 of 74; sepsis, 10 of 15; and MI, 20 of 23. chi 2 test for trend of desire to be resuscitated from the self-selected worst prognostic category by level of training demonstrated no significant decrease in desire to be resuscitated with increasing level of training. Physician's beliefs about CPR may be influenced by their experiences with particular patients and events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489678 TI - Pediatric emergency care: an annotated bibliography of the recent literature. PMID- 8489679 TI - Cricothyrotomy performed by prehospital personnel. PMID- 8489680 TI - Emergency medicine and health care reform. PMID- 8489681 TI - Atropine use in electromechanical dissociation. PMID- 8489682 TI - Side effects of clozipine (Clozaril) requiring emergency treatment. PMID- 8489683 TI - Ethyl chloride intoxication. PMID- 8489684 TI - Fracture of titanium-rigid fixation plate not clearly discernable on panoramic radiograph. PMID- 8489685 TI - Intestinal obstruction: the marble effect. PMID- 8489686 TI - Diarrhea in acquired immune deficiency syndrome (AIDS). AB - Diarrhea is a common manifestation of HIV disease which most nurses will find themselves confronting at some point. It can be extremely debilitating, as well as causing psychological distress to patients. Treatment depends on etiology; it may be successful if the diarrhea is caused by a specific enteric pathogen or a specific medication the patient is taking. However, often the diarrhea cannot be resolved and treatment must be by supportive measures. Management has three components: diet, anti-diarrheal agents, and skin care. A multidisciplinary team provides the most effective approach for managing these complex, difficult cases. PMID- 8489687 TI - Case study: carbuncle of the neck with extensive tunnelling. AB - A 40 year old female developed a carbuncle at the base of the neck on the right side near the hairline. Despite her attempts to treat the carbuncle at home "it continued to enlarge and fester" (became inflamed and suppurated). She was admitted to the hospital and, following surgical incision and drainage, ET nurse consultation was requested to establish a wound treatment regimen. PMID- 8489688 TI - A patient teaching protocol for pressure ulcer prevention and management. PMID- 8489689 TI - The wound care puzzle. PMID- 8489690 TI - Pocket wound care cards: helpful hints for wound care. PMID- 8489691 TI - ICWM consensus statement: wound management. International Committee onWound Management. PMID- 8489692 TI - Confirmation of the airborne occurrence of micron-size airborne pollen antigen carrying particles by immunoblotting. AB - We confirmed the existence of micron-size airborne particles carrying major pollen antigen of Cryptomeria japonica (Cry j l) and Lolium perenne (Lol p l) by means of an immunoblotting technique and examination by light microscopy. The size of the spots on a nitrocellulose membrane, marking the presence of antigen on the sampler's tape, varied considerably under light microscopic examination. Spots smaller than pollen grains and micron-size spots were observed together with large spots which seem to have been derived from intact pollen grains. The number of micron-size spots counted under a light microscope did not correspond with the number of spots from pollen grain observable with the naked eyes. This suggests other sources of airborne Cry j l particles than intact pollen grains alone. PMID- 8489693 TI - Optimising the extraction of allergens in Betula pollen as determined by isoelectric focusing in polyacrylamide gels. AB - Water soluble proteins extracted from birch pollen are responsible for most of the allergic symptoms in central and northern Europe as well as in parts of northern U.S.A. and Canada. Previous immunological studies of pollen allergens by isoelectric focusing (IEF) in polyacrylamide gels (PAGs) used a variety of extraction methods with little regard to standardisation or optimisation. In the present study a variety of buffers with various pH, charged buffering ions and ionic strengths were evaluated against different extraction times and temperatures in order to determine the optimum conditions for protein extraction. The largest number of proteins, determined by IEF, were found when extractions were performed at 10 degrees C and for 1 hour. Coomassie Blue and silver staining methods were compared. PMID- 8489694 TI - A forecast model for hazel (Corylus) and chestnut (Castanea) pollen emission. AB - In this paper a simple conceptual model is introduced in order to predict the atmospheric pollen concentration threshold above which pollinotics show allergic symptoms. In addition, the range of the pollen sampler with respect to the local and remote emission of pollen grains, produced by the vegetation in its flowering phase, is highlighted. Two different pollen types have been considered; their emission in the atmosphere takes place in two periods of the year, which greatly differ both in climatological respect and concerning the atmospheric of mixing particles. The data analysis is carried using a methodological approach, taking into account phenological, aerobiological and meteorological parameters. PMID- 8489695 TI - Temperature influence on differentiation and release of hazel pollen. AB - The aim of the present work was to identify the classic phenological stages, and to understand its relation to catkin differentiation and growth, and its consequences for the start of pollination. Phenological observations and an aeropalynological survey on Corylus avellana, which is an example of an economically and allergologically interesting arboreal plant, were carried out during 1991-1992. The comparison between the different phenological phases and the aeropalynological data, showed that the pollen trap recorded hazel-pollen presence in the atmosphere immediately after the pollen release from the orchard. The start of catkin elongation in late winter, after the chilling requirement has been fulfilled, could be used to indicate the beginning of heat accumulation necessary for pollination. PMID- 8489696 TI - Change in the northward movement of the pollen front of Cryptomeria japonica in Japan, during 1986-1991. AB - A map of pollen fronts of Cryptomeria japonica was compiled from pollen counts taken at 28 airborne sampling sites in Japan in 1986. Thereafter, the number of sites was increased, reaching 80 in 1991. In this way an accurate and complete map of the C. japonica pollen fronts was compiled annually. We used the results obtained from mapping the pollen fronts to draw up a map of the average locations of the front, from which the beginning of the pollen season can be predicted. A close correlation was found between the latitude of the airborne sampling sites and the mean interval between January 1 and the day pollen release began during these 6 years. PMID- 8489697 TI - Comparison of gramineae and ragweed pollen counts measured by Hirst's and Cour's traps. AB - The aim of this study is to appreciate what conclusions may be drawn from the comparison between two different methods for pollen count determination in clinical allergology. In Lyon (France), two pollen collectors are set up in two places separated by ten kilometers, as the crow flies. The Hirst-type trap is on the roof of the Pasteur Institute in the town; the Cour's trap (French Association for Ragweed Study), is located at the meteorological station in the country at the east of the town. In the Rhone-Alpes region, pollinosis is essentially due to Poacae and Ambrosia elatior. The weekly data have been recorded during three years. The results of the two categories of herbaceous plants are not comparable, except as regards the date at which the pollen season commenced. Graminae pollination (GP) commences between 20th April and 6th of May. Ragweed pollination (RP) accurately commences 5th and 6th of August! Differences in the fluctuations of peak concentrations of GP from one trap to the other can be imputed to the collectors, the site where these are located, the method used to process the data, the herbaceous weeds themselves. RPC (the dates of the peaks) are closer and more coherent. Lastly, in allergological practice, the Jacques Dechamp's rule, to only emply with the A.F.E.D.A. trap, is a hardy aid used to predict the week of the all-important peak pollen concentrations of G and R. PMID- 8489698 TI - A statistic study of atmospheric pollen in Japan. AB - By using a volumetric method, the authors made an investigation on airborne pollen grains in connection with the incidence of pollinosis since 1969, in Toho University, Funabashi, Chiba, Japan. The airborne pollen grains in each sample were counted under the microscope to identify the pollen types, and the pollen grains were classified into seven types according to the classification of pollen grains in Japan reported by Ikuse. In this report, the accumulated number of each species was analyzed statistically by circular plot, semi-logarithmic plot and test of skewness (g1) and kurtosis (g2) of frequency distribution by G. W. Snedecor. From the investigation in the years of 1969, 1970, 1990, 1991, the most frequent airborne pollen grains belonged to the 1-aperturate 3C(ab) type pollen in 1969 and 1970, and to the 1-aperturate 3B type pollen in 1990 and 1991, reflecting the change of environment during twenty years. By the g1 and g2 statistics for almost all species, the mode of distribution curve was significantly smaller than the mean, indicating that the whole distribution significantly skewed from a normal distribution, and the peak was flat for the herbs, while sharp for the trees. PMID- 8489699 TI - A simplified method for the purification of human red blood cell glyoxalase. I. Characteristics, immunoblotting, and inhibitor studies. AB - Glyoxalase I (EC 4.4.1.5) was purified from human red blood cells by a simplified method using S-hexylglutathione affinity chromatography with a modified concentration gradient of S-hexylglutathione for elution. The pure protein had a specific activity of 1830 U/mg of protein, where the overall yield was 9%. The pure protein had a molecular mass of 46,000 D, comprised of two subunits of 23,000 D each, and an isoelectric point value of 5.1. The KM value for methylglyoxal-glutathione hemithioacetal was 192 +/- 8 microM and the kcat value was 10.9 +/- 0.2 x 10(4) min-1 (N = 15). The glyoxalase I inhibitor S-p bromobenzylglutathione had a Ki value of 0.16 +/- 0.04 microM and S-p nitrobenzoxycarbonylglutathione, previously thought to inhibit only glyoxalase II, also inhibited glyoxalase I with a Ki value of 3.12 +/- 0.88 microM. Reduced glutathione was a weak competitive inhibitor of glyoxalase I with a Ki value of 18 +/- 8 mM. The polyclonal antibodies were raised to the purified enzyme and were found to react specifically with glyoxalase I antigen by immunoblotting. This procedure gave a protein of high purity with simple low pressure chromatographic techniques with a moderate but adequate yield for small-scale preparations. PMID- 8489700 TI - Refolding of cytochrome b562 and its structural stabilization by introducing a disulfide bond. AB - The packing mechanism of the secondary structures (4-alpha-helices and 3(10) helix) of cytochrome b562 is simulated by the "island model," where the formation of protein structure is accomplished by the growth-type mechanism with the driving force of packing of the long-range and specific hydrophobic interactions. Packing proceeds through the formation of the structure at the nonhelical part, where a lot of hydrophobic pairs are distributed. Consequently, conformation, nearly similar to the native one, is successfully obtained. With the help of this result, the theoretical prediction of the possibility of forming this disulfide mutant (N22C/G82C) of b562 can be performed prior to the experiments by our geometrical criterion ("lampshade"). This criterion is expected to be a significant principle for introducing possible disulfide bonds into a protein to be engineered. PMID- 8489701 TI - Conformational analysis and proteolytic processing of synthetic pre-pro-GnRH/GAP protein. AB - Homogeneous pre-pro-GnRH/GAP protein was recently synthesized in 100 mg quantities by solid-phase methods and surprisingly, the synthetic pre-pro protein, which normally does not escape the endoplasmic reticulum, was found to inhibit the release of prolactin from cultured pituitary cells. This is the first demonstration of significant biological activity associated with a precursor protein and provides the rationale for its further study. We now report the results of our initial examination of the conformational properties of pre-pro GnRH/GAP protein as a prelude to solving its solution phase conformation by homonuclear 1H-NMR protocols. Thermal and pH titration fluorescence and circular dichroism spectroscopies reveal that the protein is resistant to thermal-induced conformational changes but is particularly sensitive to pH-induced conformational changes; while Asp/Glu and Arg residues may contribute to structural stability, His and Lys residues predominate. Pre-pro-GnRH/GAP is about 30% helix in the range of 2-40 degrees C; however, even at 90 degrees C, the peptide retains nearly 50% of its helix character. There is no evidence for a cooperative transition; for this reason, differential scanning calorimetry failed to yield a defined transition thermogram. Pre-pro-GnRH/GAP apparently does not pass through a transition state as a function of temperature but appears to flex and retain a high percentage of helix structure, resulting in subtle changes in secondary structure. There is no discernible isodichroic point. On either side of the neutral pH range, however, there are dramatic changes in structure that result in nonreversible denaturation of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489702 TI - Conformation and activity of Phaseolus coccineus var. rubronanus lectin. AB - The conformation of native and denatured Phaseolus coccineus var. rubronanus lectin was studied by circular dichroism (CD) and correlated to the hemagglutinating activity. The far-UV CD spectrum at 25 degrees C showed a broad, negative band around 223 nm and a positive one at 196 nm. CD data analysis of the lectin indicated a beta-sheet-rich protein. At high temperatures, the spectrum was blue-shifted with increasing magnitude; these changes correlated well with the loss of the activity. The conformation of lectin between pH 2 and 10 remained essentially unchanged. At pH 13 the CD spectrum resembled that of unordered form with a negative band near 200 nm and the activity was completely lost. The denatured lectin in 6 M guanidine hydrochloride would be renatured upon diluting the denaturant to 0.75 M; the changes in CD spectrum again correlated well with the loss of the activity. The effect of sodium dodecyl sulfate on the lectin was drastic; it sharply increased the alpha-helix at the expense of the beta-sheet and reduced the activity; the changes reached a plateau above 20 mM surfactant. PMID- 8489703 TI - A new approach to predicting protein folding types. AB - A new method is proposed for predicting the folding type of a protein according to its amino acid composition based on the following physical picture: (1) a protein is characterized as a vector of 20-dimensional space, in which its 20 components are defined by the compositions of its 20 amino acids; and (2) the similarity of two proteins is proportional to the mutual projection of their characterized vectors, and hence inversely proportional to the size of their correlation angle. Thus, the prediction is performed by calculating the correlation angles of the vector for the predicted protein with a set of standard vectors representing the norms of four protein folding types (i.e., all alpha, all beta, alpha + beta, and alpha/beta). In comparison with the existing methods, the new method has the merits of yielding a higher rate of correct prediction, displaying a more intuitive physical picture, and being convenient in application. For instance, in predicting the 64 proteins in the development set based on which the standard vectors are derived, the average accuracy rate is 83.6%, which is higher than that obtained for the same set of proteins by any of the existing methods. The average accuracy predicted for an independent set of 35 proteins of known X-ray structure is 91.4%, which is significantly higher than any of the reported accuracies so far, implying that the new method is of great value in practical application. All of these have demonstrated that the new method as proposed in this paper is characterized by an improved feature in both self-consistency and extrapolating-effectiveness. PMID- 8489704 TI - Fluorescence quenching in riboflavin-binding protein and its complex with riboflavin. AB - Fluorescence quenching of tryptophan residues in egg-white riboflavin-binding protein by two typical quenchers (charged iodide and uncharged acrylamide) reveals acid-induced changes of protein conformation. At neutral pH, acrylamide flow in macromolecule, (i.e., the quenching effect) is decisive; tryptophan residue accessibility for iodide is small. At low pH, some tryptophan residues are exposed to the protein surface and become more accessible to iodide. In contrast, acrylamide is less able to permeate this conformational state of RBP. Fluorescence of tryptophan residues in riboflavin-RBP complex and chemically N bromosucinimide-modified RBP was quenched by iodide and acrylamide. PMID- 8489705 TI - An examination of structural interactions presumed to be of importance in the stabilization of phospholipase A2 dimers based upon comparative protein sequence analysis of a monomeric and dimeric enzyme from the venom of Agkistrodon p. piscivorus. AB - Phospholipases A2 may exist in solution both as monomers and dimers, but enzymes that form strong dimers (KD approximately 10(-9) M) have been found, thus far, only in venoms of the snake family Crotilidae. The complete amino acid sequences of a basic monomeric and an acidic dimeric phospholipase A2 from Agkistrodon piscivorus piscivorus (American cottonmouth water moccasin) venom have been determined by protein sequencing methods as part of a search for aspects of structure contributing to formation of stable dimers. Both the monomeric and dimeric phospholipases A2 are highly homologous to the dimeric phospholipases A2 from Crotalus atrox and Crotalus adamanteus venoms, and both have the seven residue carboxy-terminal extension characteristic of the crotalid and viperid enzymes. Thus, it is clear that the extension is not a prerequisite for dimerization. Studies to date have revealed two characteristic features of phospholipases A2 that exist in solution as strong dimers. One is the presence in the dimers of a Pro-Pro sequence at position 112 and 113 which just precedes the seven residue carboxy-terminal extension (residues 116-122). The other is a low isoelectric point; only the acidic phospholipases A2 have been observed, thus far, to form stable dimers. These, alone or together, may be necessary, though not sufficient conditions for phospholipase A2 dimer formation. Ideas regarding subunit interactions based upon crystallographic data are evaluated relative to the new sequence information on the monomeric and dimeric phospholipases A2 from A.p. piscivorus venom. PMID- 8489706 TI - Studies in C-terminal sequencing: new reagents for the synthesis of peptidylthiohydantoins. AB - In previous studies aimed at the sequencing of peptides and proteins from the carboxy terminus, we have derivatized the C-terminus to a thiohydantoin using acetic anhydride and trimethylsilylisothiocyanate (TMS-ITC) and subsequently hydrolyzed it to form a shortened peptide capable of further degradation and an amino acid thiohydantoin which can be identified by reverse-phase HPLC. Current limitations to this chemistry include an inability to derivatize proline and low yields with asparagine and aspartic acid residues (Bailey et al., 1992). In an attempt to solve some of these problems, we have investigated the use of reagents other than acetic anhydride for the activation of the C-terminal carboxylic acid. These include 2-fluoro-1-methylpyridinium tosylate, 2-chloro-1-methylpyridinium iodide, and acetyl chloride. Addition of TMS-ITC to peptides activated by the 2 halo-pyridinium salts formed the expected peptidylthiohydantoin, but in addition formed a peptide chemically modified at the C-terminus which was blocked to C terminal sequence analysis. This derivative was not obtained when either acetic anhydride or acetyl chloride was used for activation. Formation of this derivative was found to require the presence of an isothiocyanate reagent in addition to the halo-pyridinium salt. Sodium thiocyanate, TMS-ITC, and a new reagent for thiohydantoin synthesis, tributyltinisothiocyanate (TBSn-ITC), were all found to be capable of forming this analogue. Structural elucidation of the C terminally modified amino acid revealed it to be a 2-imino-pyridinium analogue. Formation of this C-terminally blocked peptide could be minimized by the use of the 2-chloro-pyridinium reagent, rather than the 2-fluoro reagent, and by performing the reaction at a temperature of 50 degrees C or lower. The 2-halo pyridinium reagents offer potential advantages over the use of acetic anhydride for activation of the C-terminal carboxylic acid. These include: milder reaction conditions, faster reaction times, and the ability to sequence through C-terminal aspartic acid. The TBSn-ITC reagent was found to be comparable to TMS-ITC for formation of peptidylthiohydantoins. PMID- 8489708 TI - Secondary structural changes of large and small fragments of bovine serum albumin in thermal denaturation and in sodium dodecyl sulfate denaturation. AB - The helicities in various fragments of bovine serum albumin (BSA) were examined in the thermal denaturation and in sodium dodecyl sulfate (SDS) denaturation. The thermal denaturation was examined in a temperature range between 2 and 65 degrees C. The helicity decreased with a rise of temperature and it recovered to some degree upon cooling temperature. A rather high reversibility was observed in the BSA fragments, which were located in the N-terminal of the parent protein and then contained the first large loop with no disulfide bridge. The high reversibility was available also for the helicity in the first large loop of the fragment, disulfide bridges of which were reduced. The fragments, which were smaller than one domain, became unstable in the SDS denaturation. The helicities of such fragments decreased in lower SDS concentrations compared with those of the intact BSA and the large fragments, which contained one or more domains. A resistance to the SDS denaturation appeared in the helices of every large loop even after the fragmentation. On the other hand, helicities of the fragments decreased to 20-25% upon the reduction of disulfide bridges. However, the helicities of these fragments increased to 35-40% in the SDS denaturation. PMID- 8489707 TI - Tryptophan207 is involved in the GTP-dependent conformational switch in the alpha subunit of the G protein transducin: chymotryptic digestion patterns of the GTP gamma S and GDP-bound forms. AB - The limited proteolytic pattern of transducin, Gt, and its purified subunits with chymotrypsin were analyzed and the cleavage sites on the alpha t subunit were identified. The alpha t subunit in the GTP gamma S bound form was cleaved into a major 38 kD fragment, whereas alpha t-GDP was progressively digested into 38, 23, 21, and 15 kD fragments. The beta gamma t subunit was not very sensitive to proteolytic digestion with chymotrypsin. The gamma t subunit was not cleaved and only a small portion of beta t was digested into several fragments. In order to determine which proteolytic fragment of alpha t still contained the carboxyl terminal region, chymotrypsinization was carried out using Gt previously 32P labeled at Cys347 by pertussis toxin-catalyzed ADP-ribosylation. The 32P-label was mainly associated with the alpha t subunit and a 15 kD fragment. The 23 and 21 kD fragments were not 32P-labeled. Analysis of amino terminal sequences of 38, 21, and 15 kD proteolytic bands allowed the identification of the major cleavage sites. Chymotrypsin had two cleavage sites in the amino terminal region of alpha t, at Leu15 and Leu19. Chymotrypsin removed 15-19 amino acid residues from the amino terminus of alpha t, generating two peptides (38 kD) which comigrates in gel electrophoresis. Chymotrypsin also cleaved at Trp207 in a conformation dependent manner. Trp207 of alpha t-GTP gamma S was resistant to proteolysis but alpha t-GDP and the 38 kD fragments of alpha t-GDP produced the 23 and 21 kD fragments, respectively, and a 15 kD fragment containing the carboxyl terminus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489709 TI - Structural characterization of the two refold dimers of recombinant bovine somatotropin (bST). AB - Two major dimers are generated during the folding/oxidation of inclusion bodies of recombinant bovine somatotropin (bST). These dimers represent the major part of the inactive high molecular weight species that are formed in this process. The structures of the two dimers are unambiguously determined by peptide mapping using trypsin, thrombin cleavage, and selective DTT reduction experiments. Results indicate that the formation of both dimers involves the large disulfide loop cysteines. The latter-eluting dimer from RP-HPLC, previously reported as a large loop concatenated dimer, was revised to be an antiparallel disulfide-linked dimer. On the other hand, the first eluting dimer is a concatenane in which two monomers are held together by the interlocking of the two large disulfide loops. PMID- 8489710 TI - Cell proliferation and chemical carcinogenesis: a symposium overview. PMID- 8489711 TI - How many mutations are required for tumorigenesis? Implications from human cancer data. PMID- 8489712 TI - Genetic predisposition and mesenchymal-epithelial interactions in ras+myc-induced carcinogenesis in reconstituted mouse prostate. AB - Using a mouse prostate reconstitution (MPR) model system, strain-specific responses to the ras and myc oncogenes were investigated. When ras + myc were introduced into both the mesenchymal and epithelial compartments of the urogenital sinus, poorly differentiated prostate cancer was produced at a high frequency (> 90%) in inbred C57BL/6 mice. In contrast, under similar conditions, inbred BALB/c MPRs formed benign prostatic hyperplasia that converted to cancer at a low frequency (< 10%). Restricting the oncogenes to the mesenchymal or epithelial compartments revealed that oncogene activities were more pronounced in the mesenchyme of C57BL/6 mice and resulted in elevated transforming growth factor-beta 1 expression along with a severe desmoplastic reaction. Heterologous MPRs composed of BALB/c mesenchyme and C57BL/6 epithelium or vice versa demonstrated that intrinsic properties of BALB/c mesenchyme can arrest the progression of ras + myc-initiated C57BL/6 epithelium from benign hyperplasia to malignant carcinoma. PMID- 8489713 TI - Carcinogen-induced diploid hepatocytes: sensitive target cells for transformation by mutated c-Ha-ras oncogene. AB - Sequential treatment of partially (two-thirds) hepatectomized rats with diethylnitrosamine and 2-acetylaminofluorene induces the emergence of diploid hepatocytes in rat liver. These carcinogen-induced diploid cell populations are thought to contain the progenitors of hepatocellular carcinoma (HCC), i.e., initiated, cells. In the study presented here, we addressed the question of whether putative mutations in carcinogen-induced diploid hepatocytes can cooperate with activated oncogenes in the process of transformation in vitro. Both carcinogenesis in vivo and transformation in vitro have been shown to be multistep processes requiring at least two independent transforming events. Diploid and polyploid rat hepatocytes were isolated by centrifugal elutriation. The purity of the elutriated fractions was 88 +/- 3% in the diploid fraction and 84 +/- 3% in the polyploid fraction. Hepatocytes from both the elutriated cell fractions and, for comparison, hepatocytes from untreated rats were transfected by electroporation with oncogene expression vectors containing the mutated human T24 c-Ha-ras gene and of the N-myc gene. Transient expression of transfected DNA was similar in both hepatocyte populations. No cell lines could be established by using the N-myc vector. In contrast, the carcinogen-induced diploid hepatocytes, but not polyploid hepatocytes, could be converted by transfection with the ras vector into permanent anchorage-independent growing cell lines with hepatocyte like morphology and differentiation. These cell lines expressed the myc proto oncogene and transforming growth factor-alpha constitutively. Thus, carcinogen induced diploid hepatocytes are sensitive to transformation by the ras oncogene, suggesting cooperation between putative preexisting mutations in the diploid cells and the ras oncogene product in hepatocellular transformation. PMID- 8489714 TI - Application of denaturing gradient gel blots to detect p53 mutations in X-ray transformed mouse C3H 10T1/2 clones. AB - The denaturing-gradient gel electrophoresis (DGGE) blot technique is a highly sensitive method developed to detect sequence differences (e.g., single base changes and small deletions) in genomic DNA. We used this method to screen for mutations within the p53 locus of independent X-ray-transformed C3H 10T1/2 cell clones. Genomic DNA from 29 transformed clones was digested with Haell and Hinfl endonucleases, electrophoresed on denaturing gradient gels, electroblotted onto nylon membranes, and hybridized to a radioactive p53 cDNA probe. Changes in the melting pattern of p53 were observed in DNAs from 9 of 29 X-ray-transformed clones examined. No changes were found in untransformed, wild-type 10T1/2 cell clones. These results indicate that X-ray-induced p53 mutations may contribute to cell transformation. PMID- 8489715 TI - Assessing satiation in the bottle-fed baby. PMID- 8489716 TI - Milk bank screening procedures. PMID- 8489717 TI - Inactivation of human immunodeficiency virus type I in human milk: effects of intrinsic factors in human milk and of pasteurization. AB - Human milk was inoculated with human immunodeficiency virus type I (HIV-1) or with HIV-1-infected cells in volumes and containers typically used in human milk banks. The inoculated milk was pasteurized at 62.5 degrees C for 30 minutes in a water bath, i.e., conditions currently in use or proposed for human milk pasteurization. The process of HIV-1 inoculation and pasteurization effectively inactivated the infectivity of both cell-free HIV-1 and HIV-1-infected cells. No virus was recovered after the process, even after repeated subculturing in attempts to rescue the virus. Pasteurization reduced the infectious titer of cell free HIV-1 and HIV-1-infected cells by more than 5 logs and 6 logs respectively. Human milk contains one or more components that inactive HIV-1 but that are not toxic for the cells used to replicate virus. These components have not been identified, but physical and solubility properties are consistent with characteristics of lipids. PMID- 8489718 TI - Breast pads: their effectiveness and use by lactating women. AB - The diversity of breast pads available and absence of data on their effectiveness led the Breastfeeding Association of South Africa to design laboratory simulation experiments measuring fluid retention and evaporative properties as indicators of pad surface dryness. Questionnaires distributed at four breastfeeding clinics were used to obtain data on mothers' use of pads and incidence of breast problems. The majority of mothers surveyed used a new disposable breast pad made by Johnson & Johnson. The experimental studies showed that this pad allowed no leaking and kept the breast markedly drier than other disposables. Exclusive use of these pads or cotton towelling pads did not produce a detectable increase in nipple problems. A home-made disposable breast pad using a nappy (diaper) liner encasing toilet paper was most effective at keeping the breast dry and offered good protection against leaking. Since it is economical and easy to use, it is recommended as a good alternative to expensive disposables. Clinging materials, e.g. gauze, cottonwool or paper, and panty liners, maintain excessive surface dampness and are not recommended. If used, two layers of nappy liner on the inner surface may enhance nipple dryness. PMID- 8489719 TI - Treatment of inverted nipples using a disposable syringe. AB - Seven mothers who had inverted nipples were helped to breastfeed their infants with the assistance of a simple device made from a 10 ml disposable syringe. These women were able to successfully breastfeed within one week. On follow-up, these mothers were able to sustain adequate breastfeeding. PMID- 8489720 TI - AIDS and breastfeeding: the ultimate paradox. PMID- 8489721 TI - Supporting the father when an infant is breastfed. AB - Breastfeeding is the best form of infant nutrition for mother and infant, but because it perpetuates the exclusive mother-infant relationship that existed during pregnancy, the father may feel excluded, jealous, and resentful to the detriment of breastfeeding success and the adult couple relationship. Supporting the father during breastfeeding may help improve the mother's satisfaction with breastfeeding, duration of breastfeeding, and adaptation of both parents to parenting. This paper provides recommendations for education and support related to breastfeeding based on recent research findings on the male experience of expectant and new parenthood. Recommendations based on these findings focus on anticipatory guidance about breastfeeding, anticipatory guidance to support the adult couple relationship during the transition to parenthood, and ways to enhance the father-infant relationship. PMID- 8489722 TI - Breastfeeding after pituitary resection: support for a theory of autocrine control of milk supply? AB - A 20-year-old woman with a history of pituitary resection complicated by diabetes insipidus was able to fully breastfeed for three months despite apparent hyposecretion of pituitary hormones. This case report adds to the growing body of evidence that control of milk production shifts from endocrine to autocrine control shortly after delivery. Autocrine control allows efficient regulation of milk supply to match the needs of the infant. A recently discovered factor in human milk that inhibits lactose and casein synthesis in vitro is believed to be responsible for local, short term control of milk production. This study suggests that practices which result in infrequent or incomplete removal of milk from the breast lead to decreased milk production and should be abandoned. PMID- 8489723 TI - Applying for provider status with insurance companies. PMID- 8489724 TI - Antiinfectives in breastmilk. Part III: Antituberculars, quinolones and urinary germicides. PMID- 8489725 TI - HIV and breastmilk: what it means for milk banks. PMID- 8489726 TI - On the wasting diseases of infants and children. 1885. PMID- 8489727 TI - We know where we have come from, but where are we going? PMID- 8489729 TI - A digest of the statistical report of the 1992 examination. PMID- 8489728 TI - 1-800 numbers of breastfeeding information. PMID- 8489730 TI - Is gentian violet safe? PMID- 8489732 TI - Folk wisdom, snakes, and mother's milk. PMID- 8489731 TI - Contemporary parents' needs and advice on sleep patterns. PMID- 8489733 TI - Dietitian/lactation consultant seeks others working in a children's hospital. PMID- 8489734 TI - Oversupply and retained placental fragment. PMID- 8489735 TI - The usefulness of cell surface markers in predicting the prognosis of non Hodgkin's lymphomas. AB - The Working Formulation for classification of non-Hodgkin's lymphomas provides useful prognostic information. Since this scheme was published in 1982, many studies have investigated the prognostic significance of various cell surface markers in lymphoma cases. This article reviews the value of distinguishing T cells from B cells, CD5+ B cells, immunoglobulin light chain types, proliferation antigens such as Ki 67, other markers of B-cell differentiation, and chromosomal anomalies. Each of these contributes some further prognostic significance to that already determined by the Working Formulation. PMID- 8489736 TI - [Risk of low birth weight in the Plaza de la Habana region]. AB - The objective of this study was to confirm the risk factors (RF) for low birth weight (LBW) and suggest new risk factors, which were analyzed separately and together, in order to define a program to be coordinated by family doctors to reduce the frequency of this problem. For this purpose, a retrospective cross sectional survey was carried out with 57 cases (mothers who had had LBW babies) and 58 controls (mothers who had not had LBW babies). In addition, data were obtained from the prenatal records of mothers who received care at family doctors' offices and at the clinica in the Plaza de la Habana Area. Estimates were made of the relative risk and the percentage attributable risk of 107 hypothetical RF for LBW from a clinical-epidemiological and social standpoint. One-way analysis of variance, the chi-square test, multiple linear regression, and logistic regression were used to analyze the results, which suggested the following RF for LBW: family dysfunction, family crisis, lack of spousal support, extended family, failure to attend prenatal group sessions for pregnant women, and failure to receive education on how to prevent LBW. The multifactorial risk profile was the following: risk of [corrected] intrauterine growth retardation, family dysfunction, threat of preterm delivery, coffee-drinking, attendance at fewer than 11 prenatal checkups, and failure to attend prenatal group sessions for pregnant women. The variables excluded from the model were: low weight-for height, lack of spousal support, smoking more than 10 cigarettes a day, and family history of LBW. The findings confirmed 10 of the suspected risk factors for LBW in Cuba and nine of those described in the international literature. Maternal age, spontaneous abortion, and alcohol consumption were not confirmed. Six RF for LBW preventable by the family doctor through his/her actions at the family and community level are identified, as is a multifactorial profile of six RF for LBW. On the basis of these results, proposals are made in regard to programming priorities and the implementation of strategies aimed at preventing LBW, and it is recommended that the study be continued with a larger sample. PMID- 8489737 TI - [Inter-episode continuity of primary health care: proposal for an indicator]. AB - The objective of this study was to assess the quality of the data included in patients' personal histories and to prepare an indicator of the continuity of health care between episodes of illness based on the information contained in these records. The study was descriptive. Public health specialists from the Department of Preventive Medicine of the University of Granada, Spain, participated in the design and analysis, and the field work was carried out by specialists from family and community medicine from the Zaidin-Sur Health Center of Granada, where the research was conducted in April to December 1989. For the study, 1581 personal histories were analyzed. The most complete records were those having to do with personal background (37% of the personal histories evaluated) and the most complete histories were those of pediatric patients, women, and persons who participated in programs organized by the health center. The degree of completeness of the records was low. Based on the indicator developed, only 16% of the histories at the Center contained sufficient information to allow continuity of care. It is recommended that simple records systems be created and that primary care physicians be educated in the collection of essential data. PMID- 8489738 TI - Microbial metabolism of quinoline and related compounds. XVII. Degradation of 3 methylquinoline by Comamonas testosteroni 63. AB - A bacterial strain which utilizes 3-methylquinoline as sole source of carbon, nitrogen and energy was isolated from activated sludge. On the basis of its morphological and physiological characteristics, this isolate was classified as Comamonas testosteroni. Four metabolites of 3-methylquinoline degradation were isolated from the culture supernatant and identified as 3-methyl-2-oxo-1,2 dihydroquinoline, 6-hydroxy-3-methyl-2-oxo-1,2-dihydroquinoline, 5,6-dihydroxy-3 methyl-2-oxo-1,2-dihydroquinoline and 2,5,6-trihydroxy-3-methylpyridine. Based on these results, a degradation pathway for 3-methylquinoline is proposed. PMID- 8489739 TI - Evidence that the presumptive second nucleotide interacting site on actin is of low specificity and affinity. AB - The contractile protein actin contains one mole of firmly bound nucleotide and a number of divalent cations bound with different affinities. During recent years evidence for a second nucleotide interacting site on actin has been reported. Therefore, a specific search for the presence of a second nucleotide-interacting site on actin was undertaken. For this purpose G- and F-actin or actin in complex with deoxyribonuclease I (DNase I) was passed over ADP-agarose which was found to retain all three forms of actin. Nucleotide bound to the high affinity site of actin did not exchange during passage and retention to agarose-immobilized ADP, thus indicating the presence of a second nucleotide interacting site. This site was found to be equally accessible in G- and F-actin and in the actin-DNase I complex, whereas DNase I alone passed unretained through this column. A number of nucleotides and phosphorylated compounds were tested for their ability to compete with immobilized ADP for actin interaction. It was found that all forms of actin are liberated only by high concentrations (5mM) of ADP, ATP and NADH, by 1mM CTP and ITP, and by high salt concentrations (150mM NaCl). Since it was found that EDTA- and heat-treated actin were also retained on ADP-agarose, we conclude that this second nucleotide interacting site is of limited specificity, low affinity, and not dependent on the native configuration of actin. It exhibits characteristics of an unspecific, polyanionic site, but may represent the low affinity phosphate binding site. PMID- 8489740 TI - Endogenous heterogeneity of relaxin and sequence of the major form in pregnant sow ovaries. AB - Using an extraction procedure that minimized proteolysis, followed by gel filtration, cation-exchange FPLC, and reverse-phase HPLC, the present study unambiguously showed the presence of multiple isoforms of relaxin in the ovaries of pregnant sows. Four relaxin isoforms were isolated (designated as R-I1, R-I2, R-II1 and R-III1). They had a similar migration pattern on SDS/urea PAGE, and showed no significant difference in biological activity. HPLC separation of the reduced and S-pyridylethylated relaxin variants indicated that R-I1, R-I2 and R III1 each contained multiple relaxin molecules which showed variability of the B chain, whereas R-II1 contained mostly a single relaxin molecule with only slight B-chain variability. R-II1 was thus considered likely to be the major form of relaxin stored in the ovary. Sequence analysis revealed that R-II1 contained 22 amino-acid residues in the A-chain and 29 residues in the B-chain, with a total molecular mass of 5814.8 Da. It was thus equivalent to CM-a' relaxin designated by Sherwood and O'Byrne (1974). PMID- 8489741 TI - Assisted suicide. PMID- 8489742 TI - The Roy Adaptation Model used as a guide for the nursing care of an 8-year-old child with leukemia. AB - Roy's Adaptation Model provides a framework for holistic oncology nursing practice. In this article, an overview of Roy's model is provided. It is used to assess the behaviors and stimuli influencing the behaviors of an 8-year-old boy with acute lymphocytic leukemia. Planning and evaluating the nursing care of this child is based on the model. A comprehensive list of nursing diagnoses is categorized according to Roy's four adaptive modes, and a nursing care plan for two of these diagnoses is presented. PMID- 8489743 TI - Designing a conceptual or theoretical framework for research. PMID- 8489744 TI - Practical application of an algorithm for the thrombolytic treatment of occluded vascular access devices. PMID- 8489745 TI - Health-related quality of life. PMID- 8489746 TI - Development of a preclinical model for hormonal therapy of human endometrial carcinomas. AB - Endometrial carcinoma is the most common gynaecological malignancy. Progestins are widely used in the treatment of advanced and metastatic disease with about 20 40% response rate. Attempts to develop a predictive test for progestin sensitivity of endometrial cancers are plagued by the problems of steroid receptor instability and the heterogeneous distribution of progesterone receptor. Successful development of a nude mouse model for human endometrial carcinoma has permitted a detailed investigation of the biological behaviour, hormonal modulation and resistance to progestin therapy. Use of this preclinical model should enhance our understanding of the hormonal mechanisms and lead to improved rational treatment strategies for this malignancy. PMID- 8489747 TI - The role of laparoscopic lymphadenectomy in staging and treatment of urological tumours. AB - Laparoscopic lymphadenectomy for managing a variety of urological malignancies is likely to continue to increase in popularity. It is essential that the role of these procedures be critically evaluated to ensure that they offer significant benefit without added morbidity as compared with standard techniques. The challenge for the future is to better define selection criteria for laparoscopic surgery, particularly in men with clinically localized prostate cancer, so that both staging methods and therapy can be tailored to the individual patient. PMID- 8489748 TI - Exploring pathogenetic mechanisms using transgenic animals. AB - Molecular technologies for the permanent germ-line transformation of animals are now well established and routine. These new strains of animals, called transgenic, offer an unprecedented opportunity to gain a basic understanding of human genetic disorders. In this brief review we discuss the role of transgenic animals in the creation of new models of human disease and their experimental use in biomedical research. Models are now available for the study of the genetic processes involved in the pathogenesis of neoplasia, diabetes, atherosclerosis, and developmental abnormalities. Many others are available and new ones are being produced at a great rate. Principles of gene replacement therapy are amenable to analysis with transgenic animals and the information gained will be important for the development of rational therapy. PMID- 8489749 TI - Female contraception: changing priorities. PMID- 8489750 TI - Medical consequences of 2 years' postponement of childbirth in Sweden. PMID- 8489751 TI - Hormonal intrauterine devices. AB - Intrauterine administration of progestogens from an IUD was introduced more than 15 years ago in order to improve the contraceptive efficacy and to reduce side effects. A device releasing 20 micrograms levonorgestrel daily (Levonova) with a life span of at least 5 years is now available and has been subjected to an extensive study including 1821 women followed during 5 years. The safety and efficacy were evaluated in comparison to Cu-T IUDs. The pregnancy rate (Pearl index) was 0.09. During the first two cycles after insertion intermenstrual bleeding was common, otherwise the frequency of side-effects was low. The results seem to justify the conclusion that intrauterine administration of progestogens represents a further development of IUDs and hormonal contraception. Furthermore, these devices have proven to be effective in treatment of heavy menstrual blood losses. In many menorrhagic women, use of these IUDs can replace more invasive surgical methods such as hysterectomy or endometrial resection. Intrauterine administration of progestogens is also effective in opposing the proliferative effect of oestrogen on the endometrium in women on hormonal replacement therapy. PMID- 8489752 TI - A Latin American experience with levonorgestrel IUD. AB - The intrauterine contraceptive device is an effective, safe and convenient contraceptive method. Its use in less developed countries has been limited by the increase in menstrual blood loss, an important issue in populations with a high prevalence of anaemia. The levonorgestrel releasing IUD (LNg IUD) is the first device which is at the same time highly effective, long-lasting and reduces the blood loss during menstruation. This device was tested in 200 volunteers in Santo Domingo, Dominican Republic and in 381 in Campinas, Brazil. The cumulative pregnancy rate was 0 up to 7 years of use. The reduced bleeding was confirmed, and ferritin concentration among long-term users of the LNg IUD was significantly higher than among copper IUD users and controls using no contraception. Mean levonorgestrel plasma levels remained above 100 pg/ml until the seventh year of use. Endometrial histology showed mainly a marked reduction in epithelial growth, with variable signs of decidualization of the stroma. The most important reason for discontinuation in the two centres was amenorrhea, with cumulative rates of 10 and 15, respectively. This device should be very well accepted and will have a clear niche among reversible contraceptives, when available. PMID- 8489753 TI - NORPLANT: levonorgestrel-releasing contraceptive implant. AB - NORPLANT is the newest contraceptive system to be introduced world-wide, with nearly a million current users. It consists of six Silastic capsules containing levonorgestrel (LNg), which are inserted under the skin in the arm. Release of the steroid commences immediately so that, after several weeks, circulating levels of LNg stabilize between 0.3 and 0.4 ng/ml of plasma, and they persist elevated with a minor decline for over 5 years. The gross cumulative pregnancy rate at 5 years is 2.6 per 100 woman-years. In the majority of women it produces no abnormalities in a variety of clinical chemistry, metabolic, haematological and coagulation parameters. The most common side-effect is disruption of the menstrual bleeding pattern; this is reported by two-thirds of the users in the first months and by one-third by the fifth year. Because it is the most disturbing side-effect for many users, counselling prior to insertion is of paramount importance. NORPLANT exerts varying degrees of gonadotrophin and ovarian inhibition, including anovulation and luteal insufficiency. Endometrial development is irregular and, irrespective of oestrogen levels, cervical mucus is thick and scanty at all times due to the strong antioestrogenic effect of LNg. Inhibition of sperm penetration fully accounts for the antifertility effect of NORPLANT in ovulatory cycles. The high contraceptive efficacy, lack of serious side-effects, reversibility and the convenience of long-term unattended use explain the high acceptability of NORPLANT. PMID- 8489754 TI - NORPLANT and the levonorgestrel IUD in Chinese family planning programmes. AB - NORPLANT was introduced into the Chinese family planning programmes in 1984 by the Population Council. After a pilot study of 1200 cases in four centres in China, the study was expanded to 12 centres with 10,718 cases of NORPLANT and 1208 cases of NORPLANT-2 followed up for more than 6 years. The 5 years net cumulative pregnancy rates were 0.5-1.2 and the net cumulative continuation rates were around 65-72 per 100 users. There were significant differences in pregnancy rates between different groups of body weight and age, i.e. the pregnancy rates were higher in groups with body weight over 70 kg and those aged below 25 years. The age, body weight and dependence on contraceptive effectiveness of NORPLANT should be taken into account in the selection of users. Nationwide large-scale studies in provincial and country rural areas and postmarketing surveillance are being carried out. Changes in ovarian function and endometrium have been studied. Levonorgestrel IUD (LNg-IUD) was introduced into China in 1985. Comparative clinical studies on NORPLANT and LNg-IUD, pharmacokinetic and pharmacodynamic studies and endometrial studies of LNg-IUD were performed. The higher percentage (55.1%) of ovarian suppression in Chinese users of LNg-IUD may be attributed to ethnic differences among Caucasian women in their susceptibility to steroid hormones. Results showed favourable acceptance of both devices among Chinese women. The studies promoted the incorporation of new long-acting contraceptive methods into the Chinese family planning programmes. PMID- 8489755 TI - Experience with NORPLANT in Egypt. AB - Experience with the contraceptive NORPLANT in Egypt dates back to early 1980 when the first multicentre trial was initiated. To date, more than 3000 women have received this contraceptive at the Assiut University Family Clinic alone. Analysis of the overall experience in this clinic has indicated a 5-year cumulative continuation rate of 51 and a pregnancy rate of 1.8 per 100 women. Clinical pharmacology studies pertaining to the safety of NORPLANT in our community have indicated no deleterious effect on the lipid profile, liver functions and blood coagulation system. Two studies conducted in Egypt have indicated that the initiation of NORPLANT use shortly after delivery does not have any unfavourable effect on lactational performance, or on physical or psychomotor development of the breast-fed infants. This is particularly important in Arab and Moslem cultures where prolonged breast-feeding is emphasized. A study utilizing focus-group discussion to assess users' attitudes to NORPLANT has indicated the need to improve the informational/educational package given in the service by emphasizing certain cultural considerations. On the whole, this first implant method has proven to be safe and acceptable in Egypt, where there is a special need for long-term methods for contraception, particularly as sterilization is not socially acceptable. PMID- 8489756 TI - Intrauterine contraceptive device and pelvic inflammatory disease. AB - Comprehensive, mainly epidemiological data has helped us to recognize the strongest risk factors of pelvic inflammatory disease during intrauterine contraceptive device use. These are user's exposure to sexually transmitted diseases, young age and insertion of the device. Moreover, parity of the user and type of device may affect the risk of pelvic infection. PMID- 8489757 TI - Lactational infertility in family planning. AB - The contraceptive effect of breast-feeding is the single most important determinant of human population growth rates in traditional societies without access to modern forms of contraception; lactational amenorrhoea is Nature's contraceptive. Even today, breast-feeding still prevents more pregnancies than all modern forms of contraception in many developing countries. Afferent neural inputs from the nipple pass via the spinal cord to the hypothalamus, where they cause a local release of beta endorphin. This acts to depress GnRH secretion, thereby inhibiting pituitary gonadotrophin secretion, ovarian follicular development, ovulation and menstruation. The hypothalamic beta endorphin release also inhibits dopamine production, resulting in increased pituitary prolactin secretion. The higher the suckling frequency, the more beta endorphin that is released and hence the longer the duration of lactational amenorrhoea. Lactational amenorrhoea can be relied up to give over 98% contraceptive protection to breast-feeding women in the first 6 months postpartum, regardless of their nutritional status or the time of first supplement introduction to the baby. This is because the first postpartum menstruation usually precedes the first ovulation during these early months. Once menstruation has resumed, lactation's contraceptive effect can no longer be relied upon, even though the woman continues to breast-feed. In breast-feeding women whose amenorrhoea extends beyond 6 months, there is an increasing tendency for the first ovulation to precede the first menstruation, thereby decreasing the reliability of lactational amenorrhoea as a contraceptive. Nevertheless, many women who continue to breast feed may still have up to 1-2 years of good contraceptive protection from prolonged lactational amenorrhoea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489758 TI - Contraception during lactation. AB - The probability of pregnancy is very small during the first 2 months after delivery if the mother breast-feeds. The risk remains small for 6 months if the mother is fully breast-feeding her infant, is still amenorrhoeic and the child does not receive additional food. Under these conditions there is only about a 2% chance of pregnancy. Even full breast-feeding does not inhibit ovarian function after 6 months. Breast-feeding is a very important and efficient contraceptive method in the developing countries, but it is also a useful method in developed countries during the early puerperium. Barrier methods and progestogen-only hormonal methods (pills, implants and injectables) are the primary contraceptive alternatives during breast-feeding. They have no adverse effects on lactation, the condition of the infant or on maternal ovarian function. Sterilization is only a good alternative if the family wants a permanent method of contraception. Careful insertion of an IUD is possible even before the first menstrual period. Puerperal insertion of an IUD needs expertise and training because of the vulnerability of the very soft puerperal uterine wall. Combined oral contraceptives diminish milk production and therefore combined oral contraceptives are not recommended during lactation. PMID- 8489759 TI - Postabortal contraception. AB - The return of fertility is rapid after first trimester abortion. The first ovulation may take place as soon as 2 weeks after abortion, and half of the women have ovulated by 3 weeks. Hence, commencement of effective contraception is necessary even before the first postabortal menstrual period. Women are highly motivated as regards contraception at this time. Several studies, both in developed and developing countries, have shown that the insertion of a modern copper intrauterine device (IUD) at the end of the abortion procedure is a safe and well-accepted way to start the method. Hormonal methods, such as NORPLANT, levonorgestrel-releasing IUD, injectables and oral combination pills do not affect the recovery of the pituitary-ovarian system, even though introduced immediately after abortion. The combination of preceding pregnancy, abortion procedure and immediate start of low dose oral contraceptives containing 30 micrograms of ethinyloestradiol results in a slight tendency towards hypercoagulability. This may be clinically insignificant, but it can be avoided by postponing oral contraceptives until 1 week after abortion, without losing the contraceptive efficacy of the method. PMID- 8489760 TI - Vaginal contraceptive rings. AB - Steroids diffuse through polysiloxone at a constant rate, and steroids placed in the vagina rapidly pass through the vaginal epithelium into the circulation. Combining these principles led to the development of contraceptive vaginal rings (CVR) consisting of various progestins, with and without oestrogen, placed in flexible polysiloxone, doughnut-shaped devices. As occurs with oral contraceptives, the CVRs containing progestin plus oestrogen are left in the vagina for 3 weeks and removed for 1 week to allow withdrawal bleeding, while CVRs releasing a small dose of progestins without oestrogen are left in the vagina continuously for several months. Large-scale, clinical trials were performed with a low dose levonorgestrel-releasing-only CVR by the WHO. At 1 year, continuation rates were about 50 per 100 women with 17.2 per 100 discontinuing for menstrual problems and 4.5 for pregnancy. Two sizes of a CVR containing levonorgestrel and oestradiol were studied in a multinational trial organized by the Population Council. At the end of 1 year, about half the women were continuing with the method, one-quarter had discontinued because of bleeding problems, and pregnancy rates were between 1 and 2 per 100 women. The CVR was well accepted by women and their partners, but because of lowered HDL-cholesterol levels and accelerated atherosclerosis in female monkeys, further development of this formulation was discontinued. Recently, phase II clinical trials with CVRs containing combinations of NET-acetate plus ethinyloestradiol and 3 ketodesogestrel plus ethinyloestradiol have been undertaken. These CVRs provide good bleeding control, inhibit ovulation consistently and do not have an adverse effect on serum lipids. Phase III trials with these two types of CVRs will be initiated shortly. PMID- 8489761 TI - 7 alpha-methyl-nortestosterone (MENT): the optimal androgen for male contraception. AB - Many methods of contraception involve the use of drugs that affect the secretion of hormones essential for reproduction. Oestrogens and progestins have been used for contraction in women as inhibitors of gonadotrophin secretion and ovulation. Similarly, androgens must be used in methods of fertility control for men that block gonadotrophin secretion. Androgen supplementation currently involves large, frequent doses of testosterone esters that are associated with wide fluctuations of plasma testosterone levels. Hence, there is a need for an androgen preparation that provides appropriate, continuous replacement doses over long periods. To achieve this goal, 7 alpha-methyl-19-nortestosterone (MENT), a synthetic androgen that is considerably more potent than testosterone, is suitable. As a consequence, it is feasible to administer this androgen as a substitute for testosterone for 1 year by subdermal implants. Another important feature of MENT is that it does not undergo 5 alpha- reduction in prostate as does testosterone. As a consequence, a dose of MENT sufficient to maintain normal muscle mass and gonadotrophin secretion will not hyperstimulate the prostate because its action in this organ is not amplified as is that of testosterone. Thus, MENT can be administered to men with the assurance that it will be less prone to cause diseases of the prostate than testosterone. CONCLUSIONS: (i) MENT is the first androgen that has a health benefit compared to testosterone; (ii) MENT will be promoted as one component of a two-implant system for male contraception, the other component being an implant that will release an LHRH analogue; (iii) MENT has potential uses in patients with a variety of disorders, including hypogonadism, prostatic hyperplasia and muscle wasting. PMID- 8489762 TI - Air & Waste Management Association's Government Agencies Directory. PMID- 8489763 TI - Cleavage of tumor necrosis factor-alpha by Legionella exoprotease. AB - The role of the major secretory protein of Legionella pneumophila, a zinc protease, in Legionella infection is not known. Since an important step of the host reaction in Legionnaires' disease is the production of tumor necrosis factor alpha (TNF-alpha) by alveolar macrophages, we studied the interaction of Legionella protease and U-937 cells with respect to TNF-alpha. The Legionella protease was purified by fractionated precipitation, gel filtration and hydrophobic interaction chromatography. The purified enzyme was added to U-937 cells, a promyelocytic cell line. In the supernatants of PMA-treated U-937 cells we found low concentrations of TNF-alpha after incubation with protease. Therefore we pursued the hypothesis of direct enzymatic degradation of TNF-alpha by Legionella protease. Enzymatic cleavage of TNF-alpha was proven by SDS-PAGE, ELISA and TNF-alpha bioassay with L-929 cells. The degradation of TNF-alpha by the Legionella protease was shown in all three systems. Enzymatic degradation of TNF-alpha might be important for the pathogenesis of Legionnaires' disease. PMID- 8489764 TI - Stereologic studies on collagen in bovine articular cartilage. AB - In an ultrastructural stereologic study on bovine articular cartilage we found that collagen volume density increased with increasing distance from the joint surface and from the chondrocyte. These results not only corroborate previous biomechanical data of a vertical stiffness gradient, but they also suggest that the mechanical forces are unevenly distributed horizontally. On the other hand, although mean collagen fibril diameter showed large differences between the interterritorial compartments of the three zones, there was a population of slender fibrils in all zones and compartments. Since the coarser fibrils provide the high tensile strength (Nimni 1988), the role of the slender fibrils may be to enhance the deformability of the tissue. Moreover, in spite of substantial differences in mean fibril diameter, collagen surface densities were in the same order of magnitude in the territorial and interterritorial compartments, and only slightly lower in the pericellular compartments. The surface parameter may be important for specific molecular interactions. The collagen fibrils have different polarity, i.e. the direction of the fibrils appears to be parallel and antiparallel, about 50% running in each direction. This, together with the very high length/diameter ratio (Clark 1985), may indicate that each fibril is assembled by the concerted action of many cells. The characteristic properties of articular cartilage depend on interactions between its macromolecular components, and the present quantitative data form a basis for discussions on the specificity and regulation of such interactions. PMID- 8489765 TI - Adherence and surface properties of buoyant density subpopulations of group B streptococci, type III. AB - From clinical isolates of group B streptococci, buoyant density subpopulations with variable amounts of type-specific polysaccharide can be derived. The ability of these subpopulations to adhere to vaginal epithelial cells and to glass was assessed by using [3H]-labeled bacteria. Subpopulations with no or minute amounts of capsule showed good adherence capacity and a hydrophobic cell surface. In contrast, a large capsule made the bacteria less adherent and rendered their surface hydrophilic. A negative cell surface charge, judged by determination of the z-potential, was directly related to the amount of capsule. Proteinase K treatment of less encapsulated variants significantly decreased the cell hydrophobicity. The ability of a GBS strain to express different surface characteristics may be a mechanism for adaptation to environmental changes, and may thereby contribute to the pathogenicity of GBS. PMID- 8489766 TI - Comparison of growth and susceptibility testing of pyrazinamide in different Bactec media using strains of the M. tuberculosis complex. AB - The aim of this study was to evaluate and compare growth and susceptibility testing of pyrazinamide (pza) in different Bactec media using 85 strains of the M. tuberculosis complex. Fifty-four were clinical isolates of M. tuberculosis, of which 34 strains were selected as they failed to grow in primary pza susceptibility testing. Fourteen were strains of M. bovis, 10 were different strains of M. bovis BCG, five were strains of M. africanum, and two were strains of M. microti. The following Bactec media were evaluated: (1) Bactec PZA test medium, (2) acidified Bactec 12B medium with pH reduced to 5.6, (3) acidified 12B medium supplemented with fresh egg yolk, (4) acidified 12B medium supplemented with a commercial egg yolk enrichment. Demonstration of pyrazinamidase activity was included for comparison. All strains of M. tuberculosis, M. microti and M. africanum were inhibited by pza at 100 micrograms/ml, and all strains of M. bovis and M. bovis BCG were found to be resistant to pza at 100 micrograms/ml. Bactec PZA test medium supported growth for all 85 strains tested. The two egg yolk supplemented media supported growth in all strains except one strain of M. microti, and acidified but otherwise unsupplemented Bactec 12B medium supported growth in 64 strains (75%). A pza sensitivity test result could be obtained within one week in > 79% of strains. An overall correlation of 89% between susceptibility to pza and demonstration of pyrazinamidase activity was demonstrated. PMID- 8489767 TI - A new Danish Listeria monocytogenes phage typing system. AB - A phage typing system was developed for Listeria monocytogenes. Phages were released from clinical and from food strains of L. monocytogenes by mitomycin C induction. The system consists of two subsystems, one of which is used to type L. monocytogenes serotype 1 strains, containing 12 phages, and a second which is used to type serotype 4 strains, containing 14 other phages. For the serotype 1 subsystem, the reproducibility was > or = 90%, the typability 92%, and the discriminatory power, as judged by the discriminatory index, 80%. The corresponding figures for the serotype 4 subsystem were: reproducibility > or = 94%, typability 87%, and discriminatory index 87%. The performance of the whole typing system is sufficient for it to be used for screening purposes. PMID- 8489768 TI - Mortality rate and bacteremia, endotoxin, and endothelin-1 levels in antibiotic therapy for E. coli septic peritonitis. AB - In order to study the mortality rate and bacteremia, plasma endotoxin, and plasma endothelin-1 levels in antibiotic therapy for E. coli peritonitis, blood samples were obtained from rats given intraperitoneal injections of latamoxef or placebo. Intraperitoneal injections of latamoxef improved the prognosis of peritonitis rats. Two h after treatment, bacteremia levels were noticeably higher in rats treated with placebo than in rats treated with latamoxef, but the latamoxef treated group manifested a significant elevation of plasma endotoxin and endothelin-1 levels compared to the placebo-treated group. The results of this study demonstrate that treating E. coli septic peritonitis with selected antibiotics induces increased plasma endotoxin levels, which are associated with elevation of plasma endothelin-1 levels. PMID- 8489769 TI - Effects of retinoic acid on interleukin-1 alpha and -1 beta expression by normal human keratinocytes cultured in defined medium. AB - In human epidermis, basal keratinocytes are the main source of interleukin-1 (IL 1), and IL-1 alpha is the predominant form, whereas IL-1 beta appears to exist predominantly in cultured keratinocytes. We investigated the effects of retinoic acid (RA) treatments on IL-1 alpha and -beta protein and mRNA expression of normal human keratinocytes cultured in low-calcium defined medium with or without hydrocortisone. Radioimmunoassay showed that after stimulation by RA, the IL-1 beta intracellular level is predominantly increased, with no significant modification of IL-1 alpha expression. The addition of hydrocortisone in the culture medium resulted in a decrease in RA-induced IL-1 beta overexpression, without notable modifications in untreated cultures. Release of both IL-1 alpha and -beta in culture supernatants was detectable only after RA treatment and in the absence of hydrocortisone. The overexpression of IL-1 beta in control and RA treated cultures mainly concerned the 52- and 31- to 36-kD biologically inactive precursor forms. Northern blot using specific IL-1 alpha and -beta oligonucleotide probes showed that IL-1 beta mRNA predominate over IL-1 alpha mRNA and reach a maximal level 6 h before the IL-1 beta protein peak. These findings indicate that in cultured keratinocytes intracellular IL-1 beta is preferentially increased by RA but in its immature forms. The significance of this overexpression remains to be elucidated. PMID- 8489770 TI - Porphyrin synthesis by murine epidermal cells. AB - Incubation of murine epidermal cells with delta-aminolevulinic acid (ALA) resulted in a dose- and time-dependent accumulation of porphyrins, predominantly of protoporphyrin. Porphyrin accumulation decreased in the presence of iron, and the iron-mediated decrease was partially reversed by CaMg EDTA (1.25-10.0 mM), suggesting that there is functionally active ferrochelatase in these cells. This study suggests that these cells may be a useful model for the study of cutaneous porphyrin metabolism involving ferrochelatase activity. PMID- 8489771 TI - Morphometric computerized analysis as a method to assess skin atrophy caused by corticosteroids. AB - We have employed morphometric computerized analysis to quantify changes in atrophic skin. Atrophy was induced on volunteers by means of the Duhring chamber assay, using two commercial corticosteroids with a steroid-free base as control. After 20 days, atrophy was assessed by subjective examination and rated on a five point scale. After 10 and 20 days, positive replicas of the areas under test were obtained. Photographic reproductions of these replicas were stored in the image memory of an interactive automatic computerized image analysis system, Kontron Zeiss Ibas 2, and processed with a suitable program. After selection of the measurement area by means of a circular measurement window, the 'continuous tone' image was converted to a 'binary' one by means of a dynamic discrimination function, in order to perform an automatic evaluation of the percentage area corresponding to the shadows cast by the surface markings. Morphometric computerized analysis proved to be a sensitive method for quantifying skin atrophy. A high degree of correspondence with subjective examination was shown. The method allows an objective differentiation between a mid-potency and a high potency topical corticosteroid. PMID- 8489772 TI - Transcutaneous CO2 and O2 diffusion. AB - Transcutaneous gas measurements offer a useful tool for non-invasive monitoring of skin function, but are affected by several variables that restrict their use in clinical and investigative dermatology. Skin thickness, stratum corneum and barrier function damage, blood vessel reactivity, arterial-gas concentration, skin and environmental temperature are important factors influencing transcutaneous gas flux. Improvement of techniques and standardization of methods with guidelines for operators should improve this interesting research approach. PMID- 8489773 TI - A method for the determination of viscoelastic parameters of human hair in relation to its structure. AB - An analytical model and the corresponding experimental procedure are presented, which make it possible to separately analyze the viscous and elastic components of human hair. Moreover, a computerized experimental system is described with which a standardized quantitative determination of the most important mechanical parameters of human hair can be performed. Comparative investigations of the mechanical behavior of hair specimens obtained from the frontoparietal and occipital scalp regions of 10 healthy human subjects showed no statistically significant differences with regard to their mechanical parameters. Nevertheless, the paired analysis of the mechanical parameters of thin and thick hair specimens revealed that the values of two of these parameters are significantly higher in thin than in thick hair specimens. These findings suggest that there are mechanical parameters of human hair related to gross hair morphology, whereas others depend on hair microstructure. PMID- 8489774 TI - Kinetics of sebum excretion evaluated by the Sebutape--Chromameter technique. AB - We present a novel method for studying the changing characteristics of sebum excretion of facial skin over a 3-hour period. Sebum production can be quantified by analysis of the pore patterns formed on a sebum-sensitive tape (Sebutape). We applied the CIE principles of reflectance colorimetry by measuring L*, a* and b* of Sebutapes every 15 min during 3 h of sebum collection. This combined technique yielded valuable new informations on the kinetics of sebum excretion, allowing the distinction between the follicular reservoir effect and the sebum flow. PMID- 8489775 TI - Lack of antiandrogenic effects of topical bifonazole on sebaceous glands and hairs in the hamster flank organ. AB - The activity of topically applied bifonazole was evaluated in vivo in the three androgen-dependent structures of the hamster flank organ, i.e. the pigmented spot, sebaceous glands and hairs. Topical bifonazole in our experience did not demonstrate any morphological effect on sebaceous gland and hair even when applied in the dosage of 3 mg/cm2/day. On the basis of our morphometric results we can conclude that topically applied bifonazole does not interfere with cutaneous androgen metabolic transformations in the pilosebaceous unit of the flank organ. PMID- 8489776 TI - Effect of some alkaloids, flavonoids and triterpenoids, contents of Japanese Chinese traditional herbal medicines, on the lipogenesis of sebaceous glands. AB - The effects of some alkaloids and flavonoids, which are major ingredients in some of the Japanese Kampoh drugs (Japanese-Chinese traditional herbal medicines) experientially known to be efficacious for the treatment of acne vulgaris, on the lipogenesis in the sebaceous glands of the hamster ear, an excellent animal model for the human sebaceous gland, were studied. Lipogenesis was assayed by determining 14C incorporation into sebaceous lipids extracted from the sebaceous glands which were preincubated with 14C-acetate. We found that the lipogenesis in the hamster sebaceous glands was suppressed 63 and 54% by 10(-4) M berberine (an alkaloid) and wogonin (a flavonoid), respectively. We suggest that the therapeutic effects of some Japanese Kampoh drugs experimentally used for acne vulgaris could be due to inhibition of lipogenesis by their active ingredients such as berberine and wogonin. PMID- 8489777 TI - Concentration of temarotene (Ro 15-0778) and its metabolite Ro 14-6113 in plasma and skin of hairless rat. AB - The aim of this preliminary report was to measure plasma and skin concentrations of Ro 15-0778 and its phenolic metabolite Ro 14-6113 in hairless rats receiving orally 10 mg/kg of Temarotene once daily during 10 days. Blood (2-3 ml) and skin (200-300 mg) samples were taken at different time points between 0.5 and 240 h after the last dose. We used a highly sensitive HPLC method for simultaneous determination of the two compounds with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). After 10 h, plasma concentrations of Ro 14-6113 were 5-13 times higher than for Ro 15-0778. Ro 14 6113 concentrations in the skin were 4-10 times higher than for Ro 15-0778 within the initial 48 h. The concentrations of both compounds in the skin were higher than concentrations in plasma. PMID- 8489778 TI - Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2-phosphate. AB - Ascorbic acid has been shown to stimulate collagen synthesis in dermal fibroblasts by increasing the rate of transcription of collagen genes. Experiments involving the use of ascorbic acid require daily supplementation due to the instability of the molecule in aqueous solutions. In order to provide a more stable alternative to ascorbic acid, two salts of ascorbyl-2-phosphate, having a greater chemical stability than ascorbic acid, were tested for their ability to stimulate collagen synthesis in monolayer fibroblast cultures. The concentration and time dependence of their activities were compared with ascorbic acid. The magnesium salt of ascorbyl-2-phosphate was found to be equivalent to ascorbic acid in stimulating collagen synthesis in these assays, while the sodium salt required at least a tenfold greater concentration to produce the same effect as ascorbic acid. Solutions of either ascorbic acid or the ascorbyl-2-phosphate analogs (at 10 mM) in phosphate-buffered saline (PBS) were relatively stable as shown by their decay rates and their ability to stimulate collagen synthesis even after nine days in solution prior to testing their effects on cultured cells. Ascorbic acid was unstable at neutral pH compared to solutions of either sodium or magnesium ascorbyl-2-phosphate. These data support the use of magnesium ascorbyl-2-phosphate in experiments where stability of ascorbic acid is a concern, e.g. in long-term cultures or in in vivo studies. PMID- 8489779 TI - Principles and criteria in the development and optimization of topical therapeutic products. AB - The report differentiates between dermatological and transdermal products, identifies and discusses the principles involved in the development and optimization of topical drug products. The regulatory concerns in the evaluation of topical dermatological products with respect to bioequivalence and quality control are also discussed. PMID- 8489780 TI - Transesophageal echocardiography in the diagnosis of aortic disease. AB - Transesophageal echocardiography (TEE) has recently become a major diagnostic tool in aortic disease. By far the most important role of TEE is in the rapid diagnosis of acute aortic dissection. In this disease the sensitivity and specificity of TEE are both well more than 90%, patient risk is minimal, and the test can (and should) be done in the emergency department. Limitations of TEE include, in some cases, difficulty delineating involvement of the proximal arch, major branch vessels, and abdominal aorta. Another emergency department application of TEE is the assessment of patients suspected of traumatic aortic rupture. TEE also is being applied to the diagnosis of aortic protruding atheromas, thought to have significant embolic potential. PMID- 8489781 TI - Utility of ultrafast computed tomography in the detection of thoracic aortic aneurysms and dissections. AB - The millisecond image acquisition time characteristic of the ultrafast computed tomography (UFCT) scanner makes it an ideal modality for evaluating patients with suspected vascular lesions of the thoracic aorta. Unlike conventional CT, the UFCT electron beam technology produces images with excellent resolution, minimal respiratory artifact, and superior vascular enhancement. This report discusses the (1) basic characteristics of the UFCT scanner as they relate to the imaging of the thoracic aorta, (2) UFCT appearances of uncomplicated and complicated aneurysms and dissections, (3) appropriate CT protocols used in the work-up of suspected thoracic aortic disease, and (4) strengths and weaknesses of other imaging modalities compared with UFCT. PMID- 8489782 TI - Magnetic resonance imaging of the pediatric thoracic aorta. AB - Magnetic resonance imaging (MRI) is an ideal imaging modality for investigating anomalies of the pediatric thoracic aorta. Its multiplanar capabilities allow imaging along anatomic or perpendicular planes, and clearly show the relationship between the great vessels and the airway structures. The most common pediatric aortic lesions investigated by MRI include vascular rings and coarctation of the descending aorta and its surgical complications. Other obstructive, aneurysmal, and positional anomalies of the aorta are readily demonstrated and quantified. However, precise image prescription is necessary to obtain optimal information. This review discusses and illustrates the common pediatric anomalies and current appropriate choices of imaging techniques. PMID- 8489783 TI - The thoracic aorta. PMID- 8489784 TI - Traumatic aortic injuries: current concepts. AB - This article summarizes current concepts of traumatic injuries of the aorta. The "osseous pinch" mechanism of injury is presented and discussed. The role of each imaging modality in patient evaluation is considered and a rational approach to their use suggested based on current technology and practices. PMID- 8489785 TI - The role of intravascular ultrasound in acute traumatic aortic rupture. AB - Acute traumatic aortic rupture is a lethal injury and requires immediate diagnosis and surgical repair. The standard of diagnosis for aortic rupture is aortography. In patients in whom the angiographic findings of rupture are subtle or uncertain, intravascular ultrasound (IVUS) imaging of the descending aorta has been useful in confirming or excluding mural injury. However, because IVUS is unable to provide a complete and expeditious survey of the aorta and brachiocephalic arteries, the diagnosis of rupture will continue to rely on aortography or current generation computed tomography. PMID- 8489786 TI - Magnetic resonance imaging of the thoracic aorta. AB - Magnetic resonance imaging (MRI) is steadily becoming recognized as a premier imaging modality for evaluating the thoracic aorta. Its noninvasive, nonimaging approach and refined resolution capabilities effectively combine the advantages of echocardiography, angiography, and computed tomography (CT) under the auspices of a single imaging device. On static spin-echo MRI, blood flow appears dark, allowing superb depiction of both intra- and extra vascular anatomy. With dynamic MR studies, gradient echo (cine) and phase velocity mapping techniques have proven effective in assessing the physiological consequences of anatomic vascular abnormalities in a qualitative and quantitative manner, respectively. Magnetic resonance angiography (MRA) is fast becoming a prominent vascular imaging method. Although still evolving, MRA bolsters the vascular imaging capabilities of MRI by enhancing the imaging resolution of the major branch vessels and collateral vessels. With continued advances in this area, MRI may adopt the role as the primary imaging method for assessing the thoracic aorta. PMID- 8489787 TI - Management of acute asthma. Respiratory paediatricians of Australia and New Zealand. PMID- 8489788 TI - Is prescribing paracetamol 'pro re nata' acceptable? AB - The aim of this study was to assess the prescribing pattern of paracetamol in a children's department of a general hospital. A retrospective audit of the case record prescriptions revealed that 190 of a sample of 299 children had received paracetamol during their inpatient stay. The major indications for paracetamol use were fever associated with infection in medical patients and pain following minor surgical procedures. The most common regimen was 4 hourly p.r.n. and this had the greatest potential to lead to a dose in excess of 90 mg/kg per 24 h, other than the actual prescribing of high doses on a fixed basis. This dose was actually administered to 13.6% of the children, and was prescribed for 74% of the group. We conclude that a p.r.n. regimen can lead to overdose and this may be potentially hazardous for children. PMID- 8489789 TI - Prediction of outcome of preterm infants with severe bronchopulmonary dysplasia. AB - Forty-four preterm infants of less than 30 weeks gestation and birthweight < or = 1250 g, with severe bronchopulmonary dysplasia requiring mechanical ventilation for at least 28 days, were reviewed. Twenty-seven infants (61%) survived; 17 died. There were no significant differences between survivors and non-survivors with respect to birthweight, gestational age, sex, Apgar score at 5 min or pulmonary diagnosis. Non-survivors displayed more severe changes on chest X-ray than the survivors. Peak inspiratory pressure (PIP), ventilator rate (VR), ventilator index and mean airways pressure were significantly higher in the non surviving infants on days 2, 3, 4, 7, 14, 21 and 28, with non-survivors also having significantly higher alveolar-arterial oxygen gradients and lower arterial alveolar oxygen ratios than the survivors. Discriminant analysis with cross validation by pairing PIP and VR on day 28 produced a positive predictive value for non-survival of 88% and a negative predictive value of 89%. This result was better than was obtained for any other pair of ventilator parameter or oxygenation index. Discriminant analysis by combining X-ray appearances with ventilator settings did not improve the prediction. Having established a statistical model based on the PIP and VR of ventilator-dependent preterm infants on day 28, the outcome can be predicted with a high degree of confidence. This has the immediate potential application of indicating to staff in the neonatal unit a realistic approach to take when counselling parents of these infants. PMID- 8489790 TI - Individualizing aminophylline doses in premature infants using bioelectrical impedance: a non-invasive approach. AB - The role of bioelectrical impedance (BI) in estimating the pharmacokinetics and, therefore, individualized doses, of aminophylline in preterm infants (gestational age 26-35 weeks) was assessed in a two-phase study. Multiple regression analysis in the first group of neonates (phase I, n = 19) identified resistance, reactance, weight and length as optimal predictors of distribution volume (adjusted R2 = 0.84, coefficient of variation (CV) = 10.17%), and length2/impedance and postconceptual age as predictors of clearance (adjusted R2 = 0.74, CV = 26.73%). Application of these models to an independent group (phase II, n = 20) generated doses which satisfactorily achieved target theophylline loading and steady-state (SS) 'peaks' of 10 micrograms/mL and SS 'troughs' of 7.7 +/- 0.6 micrograms/mL. A better understanding of specific criteria and limitations of the impedance technique in neonates is necessary in order to refine BI measurements. PMID- 8489791 TI - Childhood emotional and behavioural problems: a comparison of children's reports with reports from parents and teachers. AB - Paediatricians are often asked to assess children with emotional and behavioural problems and are faced with the dilemma that reports about the children's behaviour obtained from the children, and from their parents and teachers, may differ. This study compares the number of childhood emotional and behavioural problems reported by children living in the community, with the number of problems reported by their parents and teachers. When describing both internalizing and externalizing problems, the children consistently reported that they had more problems than were reported by either their parents or teachers. This pattern was particularly evident with reports from older female children who reported many more internalizing problems than were reported by their parents and teachers. Possible reasons for the differences between reports from children and the other informants are discussed. PMID- 8489792 TI - Kawasaki disease in Adelaide: a review. AB - The role of Kawasaki disease (KD) as a contributor to early childhood cardiac morbidity in Adelaide was investigated by a review of hospital admission and case note data from January 1979 to June 1990. There were 57 episodes in 55 patients. The epidemiological data in this South Australian series are similar to that seen in other Australian and New Zealand centres and correlate better with the clinical data from North America than from Japan. The average age of admission was 3.2 years (median 2.7 years) with 38 and 85% of cases being less than 2 and 5 years respectively. The male to female ratio was 1.5. The incidence of KD in the 0-5 year age group was 3.9 cases per 100,000 children. This series represents a minimum number of cases for this period and illustrates an association of aneurysm-risk with prolonged fever; improved defervescence with the combination of intravenous gamma-globulin (IVGG) and aspirin compared with aspirin alone; and a more severe disease process in the very young. The series supports the efficacy of single dose IVGG therapy. Antibiotics were given prior to diagnosis of KD in 79% of patients, often causing diagnostic confusion with possible drug reactions. The pathogenic mechanisms of KD are reviewed and a new hypothesis is proposed that incorporate mechanisms of vessel pathology resulting from release of endothelin and recognized mediators of endothelial damage including tumour necrosis factor-alpha and interleukin-1 beta. PMID- 8489793 TI - Ophthalmic assessment of physically disabled children attending a rehabilitation centre. AB - A retrospective analysis was conducted of 397 children, ranging in age from 2 to 19 years, attending the Regency Park Centre for Young Disabled in Adelaide. The disorders represented included cerebral palsy, head injury, spina bifida, severe speech and/or language disorders, muscular dystrophy and a number of less common conditions. The incidence of significant ophthalmic abnormalities in this population was 51%, with the highest incidence being 69 and 62% among children with head injury and cerebral palsy, respectively. Children with severe speech and language disorders had an incidence of 24%. Overall, routine examinations revealed previously unsuspected significant eye abnormalities in 31% of the children. A complete ophthalmic examination should be part of the evaluation of all physically disabled children to ensure early identification and treatment of abnormalities, and to optimize rehabilitation. PMID- 8489794 TI - Childhood injury mortality in New South Wales: geographical and socio-economic variations. AB - This paper reports a retrospective study of deaths due to unintentional injury in children aged between 0 and 14 years of age in New South Wales between 1985 and 1987. The aims were to determine whether the pattern of child injury mortality differed between rural and metropolitan New South Wales and to establish the relationship between socio-economic status, based on a geographical indicator of socio-economic status and child injury mortality. The child injury mortality rate for New South Wales in 1985-87 was 12.3 deaths per 100,000 population per year. The rate in the country area of 15.3 deaths per 100,000 was significantly higher than that for the metropolitan area of 11.3 per 100,000 (P < 0.05). Deaths of passengers in motor vehicle traffic accidents (P < 0.01) and deaths due to fires (P < 0.01) were greater in the country area. A negative linear association between socio-economic status and child injury mortality was found in the Sydney metropolitan area (P < 0.01). This trend was most apparent for deaths of child pedestrians (P < 0.01). PMID- 8489795 TI - Perianal group A streptococcal infection. AB - Four cases of perianal group A streptococcal infection presented with typical features of this condition; but because of lack of recognition appropriate therapy was delayed. Once group A streptococcal infection was diagnosed there was a high frequency of relapses. The need for prolonged treatment is illustrated. PMID- 8489796 TI - Adverse effects of neonatal transport between level III centres. AB - The effect of neonatal transport between level III intensive care nurseries was studied by comparing the outcome of 40 infants inborn at a regional level III centre but transported to other level III nurseries for intensive care, with 80 matched inborn controls. Transport appeared to affect respiratory status adversely but transiently. However, transported infants grew less well than control infants (32% were below 3rd centile for weight at 36 weeks vs 15% of controls), were more likely to suffer periventricular haemorrhage (40 vs 21% of controls) and had a worse neurodevelopmental outcome (70% normal at follow up vs 83% of controls). It can be concluded that for infants inborn at the National Women's Hospital, Auckland, transport to another level III centre for intensive care is associated with an increased risk of adverse outcome. PMID- 8489797 TI - Parental perception of the use and usefulness of a parent-held child health record. AB - This study surveyed 313 parents to investigate how frequently parents used a parent-held child health record, and whether they saw the record as useful. Since 1981, The Child, Adolescent and Family Health Service has distributed a Personal Health Record (PHR) to the parents of all children in South Australia. The PHR has provided each family with an ongoing record that has been consistently used for immunization, child health checks and child health screening. However, little is known about how parents view the PHR, its usefulness, and how frequently the record is used. Previous studies, generally conducted prior to, or shortly after, a parent-held child health record was introduced, have shown a poor understanding of the uses of the PHR on the part of parents and a low level of use by health professionals such as general practitioners. In contrast, the results of this study show high levels of understanding of the health record on the part of parents, and an increase in the use of the health record by general practitioners over the 10 years since the record was introduced. Although moderated by the age of the child, the sections of the PHR seen as most useful (and the most frequently used) by parents were immunization, growth charts, progress notes and health checks. PMID- 8489798 TI - Episodic central neurogenic hyperventilation in an awake child with systemic histiocytosis. AB - A 3 year old boy with systemic histiocytosis, diabetes insipidus and a lytic parietal bone lesion experienced episodes of central neurogenic hyperventilation 3 weeks after radiation to the head but was conscious and alert at presentation. At admission, the PaO2 was 133 mmHg, PaCO2 was 8 mmHg and pH 7.65. Magnetic resonance imaging revealed a pontomedullary lesion that resolved during the ensuring year. Central neurogenic hyperventilation has not been described previously as a complication of systemic histiocytosis. PMID- 8489799 TI - Mental retardation, macrostomia and hyperpnoea syndrome. AB - A syndrome with the triad of abnormalities of mental retardation, wide mouth and intermittent overbreathing is described, which has all the features of the syndrome previously described by Pitt and Hopkins. Pitt and Hopkins published two cases that bear close resemblance to each other, each having an abnormal respiratory rhythm. Both had an unusually wide mouth and palate, thick fleshy lips, broad-beaked nose, finger clubbing and abnormal electroencephalograms. This paper discusses a client living in a hostel for intellectually handicapped people who has all these features. PMID- 8489800 TI - Attitudes towards molecular genetic testing for neurofibromatosis type 1 in Western Australia. PMID- 8489801 TI - Using a computer database to record and evaluate a school screening service. PMID- 8489802 TI - Munchausen syndrome by proxy: repetitive infantile apnoea and homicide. PMID- 8489803 TI - Aluminium and infants. PMID- 8489804 TI - Paracetamol: when, why and how much. PMID- 8489805 TI - Bronchopulmonary dysplasia. PMID- 8489806 TI - Paediatrics in the Asia-Pacific region. PMID- 8489807 TI - Growth and congenital heart disease. PMID- 8489808 TI - The Australian College of Paediatrics and The Australasian College for Emergency Medicine. Policy statement. Hospital emergency department services for children. PMID- 8489809 TI - [Morgagni hernia in childhood]. AB - We report six cases of Morgagni hernia diagnosed and operated on in our pediatric surgical unit during a 14-year period. Four children were younger than 1 year and two between 1 and 2 years. Predominance in males was found. Associated congenital pathology was present in 3 children (Down's syndrome, diaphragmatic relaxation, criptorquidia and pyelo-ureteral stenosis). Predominant clinical features were respiratory infections and vomiting. In only one patient clinical onset was with respiratory distress. Plain chest x-ray was the most used diagnostic procedure. In all cases barium enema was performed to confirm the clinical diagnosis. Most frequent surgical approach was a midline supra-umbilical laparotomy. Diaphragmatic defect was left sided in 3 children and right-sided in the other 3. Transverse colon and liver were the most frequent herniated viscera. Postoperative follow-up showed no complications or recidives. PMID- 8489810 TI - [Protection by zinc acexamate against gastric lesions induced by non-steroid anti inflammatory agents]. AB - The ability of different non-steroidal anti-inflammatory drugs (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) to inhibit gastric prostaglandin E2 production in the rat was compared with their damaging potential on gastric mucosa. The influence of treatment with zinc acexamate (ZAC) on these two parameters was also determined. ZAC treatment significantly decreased the degree of gastric damage elicited by all the antiinflammatories tested. The experimental data confirm the complexity of the gastrolesive effect exerted by anti-inflammatory drugs and that only part of such effect would be related with their inhibition of prostaglandin synthesis. These results indicate that the gastroprotection of ZAC does not exclusively depend on the effect on the synthesis of prostaglandins by the gastric mucosa, yet it can additionally be exerted through alternative mechanisms. PMID- 8489811 TI - [Collagenous colitis: clinicopathologic study of 6 new cases]. AB - Collagenous colitis (CC) is a newly recognized entity characterized clinically by chronic watery diarrhoea and pathologically by epithelial inflammatory injury and the presence of a thickened collagen band beneath the surface epithelium of the colon. Clinical and pathological data of six patients (5 women and 1 man, mean age 54 years) with this diagnosis have been reviewed. Chronic watery diarrhoea was the main symptom in all cases, ranging from 2 to 12 bowel movements a day (mean +/- SD, 5.5 +/- 2.3) lasting from 8 months to 19 years (mean +/- SD, 6.6 +/ 5.9 years). Laboratory, barium and endoscopic studies showed unspecific findings. Rheumatic and thyroid diseases as well as drug allergies were found in five cases. The cause of collagenous colitis and the mechanism of diarrhoea remains undefined, being the inflammatory and autoimmune hypothesis the most likely. Diagnosis was made by multiple rectal and colonic biopsies. Pathologic findings characteristic of CC were more prominent in proximal than in distal colonic specimens. Different treatments were applied and diverse clinic responses were obtained. A review of the literature is made. PMID- 8489812 TI - [Resection of hepatic metastases of colo-rectal carcinoma. Indications and initial results]. AB - We report our initial experience in the resection of metastases from colo-rectal cancer confined to the liver. Seventeen hepatic resections were performed in sixteen patients over a thirty-eight months period. Median age was 58 years (45 75). The extent of liver involvement was assessed by computerized tomographic portography and magnetic resonance. In fourteen cases there was a solitary lesion. Mean interval time between colo-rectal resection and hepatic resection was 18 months (0-69). Twelve major hepatic resections and five wedge resections were performed. There was not operative mortality. Seven patients received complementary chemotherapy. Mean follow-up was 14.8 months (2-34). One patient died from carcinoma of the lung, five patients (31.25%) are alive with recurrence of some sort (three recurrences being in the liver) and ten patients (62.5%) are free of disease. Indications for resection, methods used for identification of candidates, prognostic determinants and indications for complementary chemotherapy are discussed. PMID- 8489813 TI - Esophageal chest pain: an unsolved problem. PMID- 8489814 TI - New provocative tests in the diagnosis of esophageal chest pain. AB - In the present experience, two new provocative tests are proposed in the diagnosis of chest pain. Exertional pHmetry, consisting in a standard ergometric test during esophago-gastric pHmetry, is employed in the diagnosis of chest pain by gastroesophageal reflux. 67 patients with non-cardiac chest pain were submitted to the test: 46 (group A) presenting pain only at rest, and 21 (group B) with exertional or mixed type of pain. Out of group A, 12 (25%) patients presented a positive response (both gastroesophageal reflux and typical pain during exercise). Out of group B, 6 (28.5%) patients responded positively, too. The diagnostic advantage of exertional pHmetry, compared to prolonged pHmetry, amounts to 21.7%. Exertional pHmetry, repeated on the following day, showed that occurrence of gastroesophageal reflux and pain are reproducible in all patients, with occurrence at the same threshold of the first test in 11 (61.1%) out of 18 patients. Endo-esophageal electrical stimulation is employed in the diagnosis of chest pain by motility disturbances: the technique is the same one of cardiological transesophageal atrial pacing. 6 healthy subjects and 21 patients with non-cardiac chest pain negative to other esophageal investigations (7 with and 14 without gastroesophageal reflux disease) were submitted to the test. 9 (43%) out of 21 patients showed a positive response, while in 2 patients (9%) we observed manometric changes without pain, and 10 (48%) showed a negative response. All the control subjects submitted to the test showed a completely negative response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489815 TI - [Hepatotoxicity induced by Droxicam: presentation of 4 cases]. AB - Hepatotoxicity has been reported with most of the nonsteroidal antiinflammatory drugs (NSAID). We describe four patients who presented hepatic injury after of treatment with Droxicam, a new NSAID prodrug of piroxicam. Hepatitis was attributed to Droxicam because of the absence of other etiological factors, temporal relation with drug administration, clinical, laboratory and histological picture and evolution favorable after the drug suppression. The hepatic injury was manifested as cholestasis and withdrawal of the drug was followed by biochemical and clinical improvement until the complete normalization in three of the four patients. Postmarketing surveillance is necessary in new drugs with unknown hepatotoxicity. PMID- 8489816 TI - [False pancreatic pseudocyst during endoscopic retrograde cholangiopancreatography (ERCP) in a gastrectomized patient]. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is a very useful procedure for the diagnosis of biliopancreatic disorders. As a mixed endoscopic and radiologic procedure, its diagnostic yield depends heavily on the quality and skillful interpretation of radiological images. Diagnostic pitfalls must be kept in mind and avoided. We report on the case of a gastrectomized patient (Billroth II), in whom the observation during ERCP of two contrast-filled cavities, suggested the diagnosis of pancreatic pseudocysts. Other imaging procedures fully ruled out this diagnosis. The cause of this diagnostic pitfall was the accumulation of contrast in the blind end of the afferent loop. Additionally, we comment on other false cystic images in the ERCP. PMID- 8489817 TI - [Sclerosing cholangitis in a patient with acquired immunodeficiency syndrome]. AB - The case of a man with the acquired immunodeficiency syndrome who had been intravenous drug abuser is reported. He was investigated because of the presence of both severe upper abdominal pain and raised levels of serum alkaline phosphatase and gamma-glutamyltransferase. The endoscopic retrograde cholangiopancreatography show stenosis of the major duodenal papilla associated with thickening and dilatation of intrahepatic bile ducts. The sclerosing cholangitis (SC) diagnostic was made with histological confirmation. Cryptosporidium oocysts were identified in sputum and bronchial lavage. We discuss his SC implication and we review the literature. We highlight the need to suspect this pathology in both positive serology human immunodeficiency patients or AIDS with abdominal pain and biochemical cholestasis. PMID- 8489818 TI - [Hepatic actinomycosis]. AB - We present a case of primary liver actinomycosis in a patient who was operated on for a duodenal ulcus seven years before. A gastrectomy was performed. His gallbladder was also removed two years before. After the surgical treatment, followed by antibiotic and chemotherapeutic treatment, with the result of a pretended success, the patient developed a liver pyogenic abscess and portal hypertension. Authors emphasise the seriousness of the illness as well as its rarity even with an accurate treatment. PMID- 8489819 TI - [Hematoma of the sheath of the anterior rectus muscle of the abdomen]. PMID- 8489820 TI - [Inflammatory fibroid polyp: an infrequent cause of intestinal obstruction]. PMID- 8489821 TI - [Intestinal subocclusion caused by gigantic mesenteric cyst]. PMID- 8489822 TI - [Intramural duodenal hematoma: report of a new case]. PMID- 8489823 TI - The Shuler nurse practitioner practice model: a theoretical framework for nurse practitioner clinicians, educators, and researchers, Part 1. AB - Because nurse practitioners (NPs) have expanded their nursing knowledge and skills into medicine they need a model that reflects this expanded role. This article presents the Shuler Nurse Practitioner Practice Model, which is wellness oriented and suggests how patient interaction, assessment, intervention, and evaluation should occur. PMID- 8489824 TI - Utilizing nurse practitioners to provide health care for elderly patients in Massachusetts nursing homes. AB - This study evaluates the nursing contribution to the process of care utilizing nurse practitioners (NPs) to provide health care for nursing home patients in Massachusetts. Using magnetic tapes of data collected through retrospective chart reviews of 2,651 patient records in 110 Massachusetts nursing homes, comparisons were made of the process of care variables of NP/physician team and physician only models of care. Results from discriminant function analysis revealed process of care variables did discriminate between the two models. The conclusion that NPs provide not only a substitutive role to that of medical care but also a complementary one should be instrumental in enabling policy decisions that encourage the full utilization of NPs. PMID- 8489825 TI - Teaching strategies used by expert nurse practitioner preceptors: a qualitative study. AB - Nurse practitioner (NP) programs utilize expert clinicians as preceptors for their students. Little is written regarding this important role. This study explored teaching strategies used by expert preceptors. Fifteen preceptors in a master's level NP program participated in this qualitative study. The study identified (a) orientation strategies, (b) strategies used with all students, and (c) strategies used differentially according to level of learner. Two distinct preceptor styles emerged from the data ("incremental structure" and "sink or swim"). Preceptors also identified characteristics of student readiness for increased responsibility. Results of this qualitative study can be helpful in preceptor orientation and continued education. PMID- 8489826 TI - Battered women: intervention and prevention. A psychosociocultural perspective, Part 2. AB - Building on the foundation of understanding and comprehensive assessment of battered women, this article addresses service planning and intervention. Strategies are approached within the framework of a Crisis Paradigm developed from field research with battered women and their families. They include mechanisms such as support groups which link crisis service to the long-term needs of battered women, and systematic approaches to removing the obstacles which keep women victimized. An Assessment and Service Planning Guide (ASPG) is proposed for inclusion in routine health care of abused women. The article concludes with strategies for preventing violence at interpersonal and societal levels. PMID- 8489827 TI - Lyme disease. PMID- 8489828 TI - A new president: renewed prospects for major health care reform. PMID- 8489829 TI - The structure, content, and quality of family nurse practice. AB - Relatively little data has been collected documenting the scope of family nurse practitioner (FNP) clinical practice, and virtually no research definitively describes the quality of that practice. Physicians have led the way in quantitative collection of practice content information. The resulting analyses have determined not only the most common diagnoses in primary care but also the content of teaching and research in family practice. Nurse clinicians, educators, and researchers have assumed this content to be pertinent to FNP practice as well. This article describes the major studies of family physician practice and the few studies of nurse practitioner/FNP practice, and advocates intensified review of FNP clinical content as an empirical basis for practice, education, and research. PMID- 8489830 TI - High-osmolar and low-osmolar contrast media. An update on frequency of adverse drug reactions. AB - During the past 3 years a great number of papers about adverse drug reactions to intravascular injection of high-osmolar and low-osmolar iodinated contrast media (CM) have been published. They include observational studies, randomized trials, meta-analyses and committee reports. Thorough analysis of this material substantiates an improvement in safety of at least 6-fold using nonionic low osmolar CM compared with ionic high-osmolar CM. The point where only a small minority is continuing to argue effectively that low-osmolar CM are not better than conventional high-osmolar CM has now been reached. High-osmolar CM are used less and less for intravascular purposes, and, in fact, have been totally replaced by low-osmolar CM in 4 countries. PMID- 8489831 TI - Incidence of roentgen contrast medium reactions after intravenous injection in pre-registration trials and post-marketing surveillances. AB - The relative risk of adverse drug reactions of ionic versus non-ionic contrast media injected i.v. were compared for different types of trials using odds-ratio. The absolute and relative risk found in large post-marketing trials were compared with that found in the iohexol pre-registration trials. The absolute risks were 2 to 10 times higher in the pre-registration trials compared to the post-marketing surveillances. The relative risk for all adverse drug reactions was 3 to 6 times higher for ionic vs. non-ionic media and independent of pre- or post-registration studies. The odds-ratio seems to be a feasible method of comparing the relative risk of adverse reactions in various trials. PMID- 8489832 TI - Effect of low-osmolality contrast media on red cell filterability. AB - The effects of low-osmolality contrast media (CM) on red blood cell (RBC) filterability were investigated using a recently developed nickel mesh filtration method. The conventional hypertonic CM iothalamate, low-osmolality iohexol, and the recently synthesized iomeprol were studied. Among them, the osmolality of iomeprol was the lowest. The impact of CM osmolality, viscosity, and iodine content on the RBC filterability was analyzed. Under equal iodine content or viscosity condition, the filterability order of RBCs suspended in CM was iomeprol > iohexol >> iothalamate, because of the osmolality of CM. Iomeprol caused small echinocytic changes but these had a negligible influence on RBC filterability. In conclusion, the osmotic effect of CM on RBC filterability is more predominant than the other CM effects, and iomeprol is the preferred CM for RBC filterability. PMID- 8489833 TI - Contrast media-induced renal morphologic lesions in diabetic rats. AB - Diabetes mellitus was induced in rats with streptozotocin and after 3 months the animals (n = 48) received an i.v. injection of 1 or 3 g I/kg in the form of high osmolar diatrizoate, low-osmolar iopromide or iohexol, or of 0.6 g I/kg of high osmolar Gd-DTPA. The controls were given an i.v. injection of physiologic saline. After 2 hours the kidneys were fixed by perfusion and the renal morphologic changes were semiquantitatively analyzed by two independent observers unaware of the agent administered. The contrast media (CM) induced pronounced cytoplasmic vacuolization in the proximal convoluted tubular cells. Such a lysosomal alteration may indicate CM uptake into the cell, and the ultrastructural evaluation revealed intracellular injuries related to the process. The alterations were most marked following administration of iohexol, but diatrizoate also induced a statistically highly significant vacuolization (p < 0.001). The lysosomal alterations following iopromide administration were not as striking, and Gd-DTPA induced only minor changes. PMID- 8489834 TI - Acute electrolyte disturbances in coronary sinus during left coronary arteriography in man. AB - Electrolyte disturbances, particularly reduction of ionized calcium, induced by iodinated contrast media (CM) are important considerations in coronary arteriography. A study was conducted in 24 patients to evaluate the acute electrolyte alterations in the coronary sinus during left coronary arteriography. During left coronary arteriography, coronary sinus blood was withdrawn for measurement of electrolytes. The CM used were diatrizoate, ioxaglate, iohexol, and iopamidol. The hematocrit was decreased moderately by all 4 CM used at 5 s and returned to the control level at 15 s. The level of ionized calcium was decreased by all CM at 5 s. Prolonged reduction of ionic calcium was observed with diatrizoate and ioxaglate at 15 s. The level of potassium was almost unchanged by diatrizoate and ioxaglate in spite of hemodilution, which may lead us to a hypothesis that potassium can be released from the intracellular spaces such as red blood cells and vascular endothelial cells. Thus the depression of left ventricular function might be caused not only by reduction of ionized calcium, but also by a relative increase in the level of serum potassium. PMID- 8489835 TI - Increased urinary excretion of iohexol after enteral administration in patients with ileal Crohn's disease. A new test for disease activity. AB - Iohexol is a water-soluble contrast medium that is partly absorbed/permeated through mucosa of the small bowel and excreted unchanged in the urine. Iohexol was administered orally to 12 patients with Crohn's disease of the ileum and to 10 healthy controls to measure its excretion in the urine. The location and activity of Crohn's disease were determined by barium double-contrast radiography in all patients and by ileoscopy and biopsy in 9 patients. Iohexol concentrations in serum and 24-hour urine were measured using reversed phase high-performance liquid chromatography. Urinary excretion of iohexol was significantly greater in patients with active Crohn's disease than in controls. We suggest this method as a new way of measuring Crohn's disease activity and mucosal damage in the small bowel. Bowel inflammation and mucosal cell damage are strongly indicated if the iohexol excreted in the urine is over 1% of the oral intake. PMID- 8489836 TI - Iodixanol in abdominal digital subtraction angiography. A randomized, double blind, parallel trial with iodixanol and iohexol. AB - The safety, tolerability and efficacy of iodixanol 270 mg I/ml were compared to those of iohexol 300 mg I/ml in a double-blind, randomized, parallel abdominal intra-arterial DSA phase III trial. Fifty-nine patients were included in the trial; 39 patients received iodixanol and 20 received iohexol. The mean volume of iodixanol administered was 235.8 ml (0.93 g I/kg b.w.) while the mean volume of iohexol was 254.7 ml (1.10 g I/kg b.w.). No differences in diagnostic information and radiographic density were apparent in spite of the difference in the concentration of iodine. No serious adverse events occurred. Four patients (10%) in the iodixanol group and 2 (10%) in the iohexol group experienced adverse events. Eight percent of the injections of iodixanol promoted discomfort, compared to 12% of the injections of iohexol. An increase in S-urea and S creatinine was seen with both agents the first day after injection, but appeared to be less pronounced with iodixanol than with iohexol. Other serum tests revealed no changes of clinical importance. Both iodixanol and iohexol were found to be effective, safe and well tolerated contrast media for abdominal intra arterial DSA. PMID- 8489837 TI - Reduced risk of ventricular fibrillation by balancing sodium, calcium, potassium and magnesium added to nonionic contrast media. An investigation in the isolated rabbit heart. AB - The effect of addition of calcium, potassium and magnesium to iohexol (350 mg I/ml) enriched with 30 mM sodium was investigated with regard to ventricular fibrillation (VF) in isolated rabbit hearts. Enriching iohexol containing 30 mM sodium with increasing amounts of calcium (0-1.2 mM) caused an increase in the frequency of VF. Increasing amounts of potassium (0-3.8 mM) to iohexol with 30 mM Na + 0.15 mM Ca + 0.1 mM Mg reduced the risk of VF. However, this protective effect of potassium on VF was reduced if magnesium was removed from the test solution. Furthermore, increasing amounts of magnesium (0-1.2 mM) to iohexol with 30 mM Na + 0.15 mM Ca + 0.4 mM K led to an increased frequency of VF. Iohexol with 30 mM Na + 0.3 mM Ca + 0.9 mM K + 0.3 mM Mg caused no VF. It is of interest to add multiple cations to sodium-containing nonionic media to improve cardiac contractility following coronary perfusion. The present study indicates that it is possible to enrich iohexol 350 mg I/ml + 30 mM Na with calcium, potassium and magnesium in small amounts, and balanced with respect to each ion, without changing the risk of VF. PMID- 8489838 TI - Expandable metallic endoprostheses for biliary obstruction. AB - Expandable metal stents (20 Gianturco Z-stents and 1 Strecker stent deployed through 8.5 F sheaths) were used with initial success for palliating bile duct obstruction in 10 patients, 8 with malignant and 2 with benign strictures. Short term failure occurred in one patient after 2 weeks, one died of unrelated causes after 10 days, and one remained jaundiced due to fulminant liver metastases. In the remaining 7 patients the obstruction was markedly palliated, with normalization of the serum bilirubin. Four have died without recurrent bile duct obstruction after a mean of 5.9 months, the 2 with benign strictures are well after 4 and 7 months, and one patient is presently palliated with a plastic endoprosthesis following reocclusion after 4 months. Expandable stents were easier to insert than conventional percutaneous endoprostheses of plastic polymers, and had longer patency in several patients, but reocclusion by tumor growth remains a constant threat in malignant disease. Metallic stents may be the therapy of choice in recurrent benign strictures, although the definitive conclusion needs longer observation and larger materials. PMID- 8489839 TI - Electrolytic stents to inhibit tumor growth. An experimental study in vitro and in rats. AB - Obstruction of metallic stents used in the management of malignant biliary strictures is common and in several cases due to tumor growth through the stent wall. In an experimental animal model in rats, a tumor was implanted subcutaneously adjacent to different metallic stents. Ingrowth of tumor through the wall of these stents was frequent. A stent generating direct electric current on the basis of electrolysis was developed and tested in vitro and in the experimental model. The study confirms that an "electrolytic" stent can inhibit ingrowth of tumor. PMID- 8489840 TI - Treatment of tuberculous bronchial stenosis with expandable metallic stents. AB - Gianturco expandable metallic stents were placed in 5 patients with dyspnea on exercise due to tuberculous bronchial stenosis. The stents were placed after dilatation with a 10-mm diameter high pressure balloon catheter. In all 5 patients, obstructive changes disappeared following the procedure, and dyspnea on exercise improved markedly. No complications related to the procedure were encountered. At follow-up during a period of up to 38 months, 2 patients showed bronchial restenosis at 11 and 17 months, respectively, after stent placement. Restenosis by granulomatous tissue was successfully treated by laser ablation. One patient showed slight one-day hemoptysis 26 months after stent placement. PMID- 8489841 TI - Percutaneous rotational lithotripsy of urinary bladder stones. Clinical results with the Rotolith lithotriptor. AB - Mechanical rotational lithotripsy of urinary bladder stones, up to 20 mm in diameter, was performed in 6 male patients with the Rotolith lithotriptor. The lithotriptor was introduced through a 10 F (OD 3.3 mm) suprapubically inserted sheath, and the procedure was performed under intermittent fluoroscopy and inspection through a transurethral cystoscope. In 3 patients, the bladder stones were fragmented to pieces small enough to be evacuated through the cystoscope. The instrument, which is designed for lithotripsy of gallbladder stones, was less efficient for fragmentation of urinary bladder calculi, primarily due to the large volume of the human urinary bladder, and possibly because of the higher gravity of bladder stones. There was no substantial damage to the mucosa of the urinary bladder. PMID- 8489842 TI - Percutaneous rotational lithotripsy of gallbladder stones. Clinical results with the Rotolith lithotriptor. AB - Ten patients (aged 39-94 years) with cholecystolithiasis were selected for percutaneous rotational lithotripsy with the Rotolith lithotriptor either because they were considered high-risk patients for cholecystectomy or because they had refused surgery. The procedure was completed in 7 patients. Five of these were stone-free at cholangiography 1 to 2 days after lithotripsy. Conclusive cholangiograms were not obtained in 2 patients due to gallbladder leakage, which in itself did not cause any serious sequelae. At ultrasonography after one month, one of these 2 patients had no visible gallbladder, the other one had small residual gallbladder stones. Rotational lithotripsy is an alternative to cholecystectomy in patients at high surgical risk, especially elderly patients who have undergone cholecystostomy as an emergency treatment for acute cholecystitis. PMID- 8489843 TI - Changes in intracranial morphology, regional cerebral water content and vital physiological variables during epidural bleeding. An experimental MR study in dogs. AB - Epidural bleeding was produced in 8 anaesthetised and heparinised dogs by an artificial system. Changes in vital physiological variables were related to intracranial shifts and tissue water content assessed with MR imaging. Six animals survived while 2 succumbed. In the surviving animals intracranial shifts and compressions remained unchanged from an early stage. The cerebral perfusion pressure was reduced from between 80 and 110 mm Hg to between 40 and 60 mm Hg. Some increase in supratentorial white matter tissue water was observed. In the lethal experiments cerebral perfusion pressure fell to less than 40 mm Hg. Moreover, secondary delayed anatomical changes were seen including hydrocephalus. Increase in cerebral tissue water was more intense and widespread than in the survivors. These findings indicate that the outcome of epidural bleeding is related to cerebral perfusion pressure with secondary deterioration resulting from additional volume loading from increased tissue water and hydrocephalus. PMID- 8489844 TI - Progressive brain compression. Changes in vital physiological variables, correlated with brain tissue water content and brain tissue displacement. Experimental MR imaging in dogs. AB - Continuous recording of vital physiological variables and sequential MR imaging were performed simultaneously during continuous expansion of an epidural rubber balloon over the left hemisphere in anaesthetised dogs. Balloon expansion led to a progressive and slightly nonlinear rise in intracranial CSF pressures and a fall in local perfusion pressures. Changes in systemic arterial pressure, pulse rate, and respiration rate usually appeared at a balloon volume of 4% to 5% of the intracranial volume (reaction volume), together with a marked transtentorial pressure gradient and MR imaging changes consistent with tentorial herniation. Respiratory arrest occurred at a balloon volume of approximately 10% of the intracranial volume (apnoea volume), which was associated with occlusion of the cisterna magna, consistent with some degree of foramen magnum herniation. Increase in tissue water was observed beginning at approximately the reaction volume, presumably due to ischaemic oedema, due to the fall in perfusion pressures. PMID- 8489845 TI - Brain atrophy in neurodegenerative diseases. Quantitative and qualitative CT analysis. AB - A quantitative and qualitative analysis was done of 187 CT examinations in 59 healthy subjects and 128 patients with various neurodegenerative diseases. The rates of agreement between quantitative measurements and the qualitative grading by two observers were 76.7% for the evaluation of lateral ventricular size and 66.3% for the assessment of sulcal size. Increase in the width of the 3rd ventricle, in the bi-caudate span, and in the area of the lateral ventricles reflected a pathologic enlargement of the ventricles. The profile of ventricular dilatation in dementia patients was different from that of other patients with brain atrophy. However, the quantitative measurement of brain atrophy by a computer-based method did not increase the differential diagnostic accuracy among dementia patients. The results stress the importance of the selection of valid measures in the evaluation of structural changes of the brain. We suggest the use of reference scans for improving the reliability of the visual evaluation. PMID- 8489846 TI - Gallbladder necrosis following hepatic artery embolization. A new indication for percutaneous US-guided cholecystostomy? PMID- 8489847 TI - Ultrasound-guided tumor biopsy in the anterior mediastinum. An alternative to thoracotomy and mediastinoscopy. PMID- 8489849 TI - The art of value--added interviewing. PMID- 8489848 TI - Ten tips for telling people what they don't want to hear. PMID- 8489850 TI - Nurse executives share their first-class ideas: Kathy McDonagh on value-added interviewing. PMID- 8489851 TI - Action audits: a communication strategy. PMID- 8489852 TI - Power talk in health care organizations. PMID- 8489853 TI - The Electromation decision: yesterday notions for a tomorrow world. PMID- 8489854 TI - Separate contributions of large- and small-scale dynamics to the heat capacity of proteins. A new viscosity approach. AB - We present here a theoretical description and experimental verification of a novel method of separating large-scale (LS) and small-scale (SS) dynamics contributions to the heat capacities of proteins in solution by using viscosity dependences. It was assumed that the LS dynamics, related to the thermal fluctuations of domains and subunits, is dependent on solvent viscosity within a sucrose concentration of 0-15% w/v, in contrast with the SS dynamics, which are related to fluctuations of atoms and amino acid residues. The results obtained with immunoglobulin G, hemoglobin and cytochrome c were in reasonable accordance with the previous data achieved by a spin-label method: the LS dynamics decrease, whereas the SS dynamics increase within the temperature elevation. The changes are dependent on the stage of the active sites of the proteins. The internal compensation of molecular dynamics between the LS and SS fluctuations may be an important factor in the design of thermostable enzymes and proteins. A new phenomenon concerning the ability of macromolecules to increase free volume in water as a result of ice-like clusters stabilization is revealed. PMID- 8489855 TI - Coronary flow reserve. PMID- 8489856 TI - Starting treatment with angiotensin converting enzyme inhibitors in heart failure: how, where, and how much? PMID- 8489857 TI - How sound is the evidence that thrombolysis increases the risk of cardiac rupture? PMID- 8489858 TI - Impaired coronary flow reserve immediately after coronary angioplasty in patients with acute myocardial infarction. AB - OBJECTIVE: To examine coronary flow reserve immediately after emergency coronary angioplasty in patients with acute myocardial infarction. DESIGN: A 3 F coronary Doppler catheter was used to measure coronary blood flow velocity in the infarct artery and in the non-infarct artery. Maximal hyperaemia was produced by 10 mg of intracoronary papaverine and coronary flow reserve was calculated. PATIENTS: 11 patients with acute myocardial infarction undergoing both emergency coronary angioplasty (4.7 (3.6) h after the onset of chest pain (mean (SD))) and at follow up catheterisation 16 (4) days after angioplasty. SETTING: Hiroshima City Hospital. RESULTS: There was no stenosis of > or = 50% in the coronary artery of interest. Immediately after coronary angioplasty the mean (1 SD) coronary flow reserve of the infarct artery was significantly less than that of the non-infarct artery (1.4 (0.4) v 2.8 (0.8), p < 0.001). At follow up catheterisation the coronary flow reserve of the infarct artery increased almost to the value of the non-infarct artery (2.8 (1.2) v 3.1 (0.8) p = NS). CONCLUSION: The coronary flow reserve in the infarct region was severely impaired immediately after reperfusion, even with a widely patent infarct artery. This could restrict the beneficial effects of reperfusion therapy, especially when there is a severe residual stenosis. PMID- 8489859 TI - In vivo detection of endothelium dependent and independent pulmonary artery relaxation in children. AB - BACKGROUND: In vitro studies have suggested an important role for the endothelium in the control of pulmonary vascular tone, but endothelium dependent and independent relaxation of pulmonary arteries have not been studied in children in vivo. METHODS: The response of the pulmonary circulation to graded infusions of acetylcholine (an endothelial dependent vasodilator) and to nitroprusside (a dilator not dependent on endothelium) was studied in 10 children aged four to 16 years who had normal pulmonary haemodynamics. Arterial diameter was measured by quantitative angiography, and pulmonary blood flow velocity was measured with a 3F intra-arterial Doppler catheter placed in a lower lobe segmental artery. RESULTS: There was a dose dependent increase in flow velocity in response to acetylcholine (maximum response 93%) (SEM 7%), and an increase of 51% (8%) in response to nitroprusside. By contrast, segmental artery diameter was unchanged during acetylcholine infusion in all patients, and increased only modestly in response to nitroprusside (5% (1%)). CONCLUSIONS: The most important site of action of endothelium dependent and independent pulmonary vasodilators is distal to the segmental pulmonary arteries. Despite low resting tone in the pulmonary circulation, endothelium dependent vasodilatation can be shown in vivo. This may allow study of the role of endothelial dysfunction in children with abnormal pulmonary haemodynamic secondary to congenital heart disease. PMID- 8489860 TI - Transient myocardial ischaemia after acute myocardial infarction does not induce ventricular arrhythmias. AB - OBJECTIVE: To see whether transient myocardial ischaemia on ambulatory monitoring after myocardial infarction is associated with ventricular arrhythmias. DESIGN: A prospective study. SETTING: The coronary care unit, general medical wards, and cardiorespiratory department of a major teaching hospital. PATIENTS: 203 consecutive patients without specific exclusion criteria admitted with acute myocardial infarction. INTERVENTIONS: 24 hour ambulatory electrocardiographic monitoring for ventricular arrhythmias and ST depression both early (mean 6.3 days after infarction, n = 201) and late (mean 38 days, n = 177). MAIN OUTCOME MEASURES: Episodes of myocardial ischaemia were identified during ambulatory monitoring by transient ST depression of > or = 1.0 mm lasting for > or = 30 s. Ventricular arrhythmias were single extrasystoles, couplets, or ventricular tachycardia. RESULTS: All ventricular arrhythmias were significantly more frequent in late than early monitoring. The arrhythmias included couplets (in 83/174 (48%) v 49/200 (25%) of patients, p = 0.0000028) and ventricular tachycardia (29/174 (17%) v 15/199 (8%), p = 0.0064). Patients with ST depression (29 early; 56 late), compared with those without ischaemia, did not experience a significant increase in single extrasystoles, couplets (31% v 23% early; 47% v 48% late), or ventricular tachycardia (3% v 8% early; 18% v 16% late). Even patients with frequent (> or = 3 episodes), and deep (> or = 1.5 mm) or prolonged (> or = 20 min) ST depression had no increase in arrhythmias. CONCLUSIONS: Ventricular arrhythmias after myocardial infarction are not associated with transient myocardial ischaemia during daily activities. This study does not support the belief that to abolish silent ischaemia would reduce the incidence of sudden death due to uncontrollable ventricular arrhythmias after myocardial infarction. PMID- 8489861 TI - Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome. AB - OBJECTIVE: To assess treatment with fludrocortisone in vasodepressor carotid sinus syndrome. PATIENTS AND METHODS: Eleven patients, mean (SD) age 83 (5) years, with daily dizzy episodes and a median of five (range two to 20) syncopal episodes over a median of one year were studied. All had vasodepressor carotid sinus syndrome (> 50 mm Hg fall in systolic blood pressure during carotid sinus massage independent of bradycardia). Carotid sinus massage was carried out while the patient was supine and upright (tilt table) before and after 600 micrograms intravenous atropine. Phasic heart rate and blood pressure recordings were monitored throughout. The study was repeated after 100 micrograms of fludrocortisone daily by mouth for two weeks. Patients continued to take fludrocortisone for a six month follow up period. RESULTS: Baseline systolic blood pressure was (mean (SD)) 169 (31) mm Hg and the RR interval was 770 (150) ms. After carotid sinus massage, systolic blood pressure fell to 113 (27) mm Hg (p < 0.01) and RR was 1060 (210) ms (NS). The vasodepressor response was 56 (12) mm Hg. Baseline systolic blood pressure after two weeks of fludrocortisone treatment was 171 (37) mm Hg (NS); but the fall in systolic blood pressure during carotid sinus massage was significantly reduced (32 (14) mm Hg; p < 0.01). At six months follow up, two patients complained of intermittent dizziness and no patients had syncope. CONCLUSION: Fludrocortisone effectively reduces the vasodepressor response and relieves the symptoms of vasodepressor carotid sinus syndrome. PMID- 8489862 TI - Abnormal autonomic modulation of QT interval in patients with idiopathic ventricular tachycardia associated with clinically normal hearts. AB - BACKGROUND: Idiopathic ventricular tachycardia (VT) occurs in a small but important subset of patients without clinically overt heart disease. The mechanism of the arrhythmogenesis remains unclear in these patients. This study examines modulation of the QT interval by the autonomic nervous system in a group of patients with idiopathic ventricular tachycardia. METHODS: Cardiac autonomic activity and ventricular repolarisation were studied in 27 patients with VT associated with a clinically normal heart (NHVT) and in 20 normal subjects. All the patients were in sinus rhythm, had normal atrioventricular conduction, and were in a drug free state. Cardiac efferent autonomic activity was measured by spectral analysis of heart rate variability from 24 hour ambulatory electrocardiograms on a Holter analysis system (Marquette). Ventricular repolarisation was evaluated by measuring the QT intervals from the same 24 hour Holter tapes at one hour intervals. RESULTS: There was no difference in any of the QT interval variables including the maximum, minimum, and mean of both the QT interval and its corrected value (Bazett's formula) between patients with NHVT and normal subjects. The high frequency component (0.04-0.15 Hz) of heart rate variability was significantly decreased in patients with NHVT compared with normal subjects (16 (8) v 21 (12) ms, p < 0.05). There was a significant correlation between the spectral variables of heart rate variability and the mean, maximal, and minimal QT intervals in normal subjects, whereas the relation was lost in patients with NHVT. No difference was found in mean heart rate between normal subjects and patients with NHVT (70 (9) v 72 (13) beats/min, NS). CONCLUSIONS: The high frequency component of heart rate variability is significantly decreased and the relation of QT interval to heart rate variability is significantly altered in patients with NHVT as compared with normal subjects. These findings suggest that abnormal modulation of the QT interval by the autonomic nervous system may play an important part in the arrhythmogenesis of NHVT. This might result from impaired vagal efferent cardiac activity in these patients. PMID- 8489863 TI - Radiofrequency ablation of accessory atrioventricular pathways: predictive value of local electrogram characteristics for the identification of successful target sites. AB - BACKGROUND: Radiofrequency catheter ablation of accessory arterioventricular pathways has been shown to be a highly effective treatment in patients with paroxysmal superventricular tachycardia. There is, however, considerable variability in the number of attempted ablation sites, contributing to lengthy operations in some cases. The purpose of this study was to investigate the predictive value of local electrogram characteristics for the identification of successful target sites. METHODS AND RESULTS: Local bipolar electrograms from 60 patients recorded at 568 sites of attempted ablation were analysed. There were 511 sites at which ablation was guided by antegrade mapping, with 49 successful sites and 462 failed sites including 61 at which accessory pathway conduction was blocked temporarily. In multivariate analysis, the time of local ventricular activation relative to onset of the QRS complex (QRS-V interval) (p < 0.001) and the presence of a possible accessory pathway potential (p < 0.05) were found to be independent predictors of successful outcome, whereas the atrioventricular interval, atrioventricular amplitude ratio, stability of local electrogram, and presence of continuous electrical activity were not. A QRS-V interval of < or = +10 ms identified successful sites with a sensitivity of 98%, but the positive predictive accuracy was only 11%. Even a QRS-V interval of < or = 20 ms resulted in only a 24% probability of success with a sensitivity of just 18%. Combining the QRS-V interval with the presence of a possible accessory pathway potential greatly reduced the sensitivity at all cut off values, but failed to increase positive predictive accuracy above 25%. There were no significant differences in electrogram characteristics between the successful sites and the sites at which conduction of the accessory pathway was interrupted transiently. There were 57 sites (nine successful, 48 failed) at which ablation was guided by retrograde mapping, but none of the local electrogram characteristics analysed emerged as independent predictors of successful pathway ablation. CONCLUSION: Local electrogram characteristics used to guide radiofrequency catheter ablation are all associated with a low positive predictive accuracy, which significantly contributes to duration of the operation. It is unlikely that this problem will be resolved solely by modification of the mapping techniques. It could require advances in catheter technology and power sources to enable larger tissue lesions to be delivered more reliably than is possible with the equipment in current use. PMID- 8489864 TI - Rapid increase in plasma endothelin concentrations during percutaneous balloon dilatation of the mitral valve in patients with mitral stenosis. AB - OBJECTIVE: To investigate the relation between plasma concentrations of immunoreactive endothelin and haemodynamic variables before and after percutaneous transvenous balloon dilatation of the mitral valve. DESIGN: Prospective study. SETTING: National cardiovascular centre. PATIENTS: 25 patients with mitral stenosis and 26 healthy volunteers. MAIN OUTCOME MEASURES: Plasma concentrations of immunoreactive endothelin were measured in the pulmonary artery, left atrium, ascending aorta, and femoral vein before and after balloon dilatation of the mitral valve. RESULTS: Peripheral venous concentrations (mean (SD)) of endothelin were higher in the patients with mitral stenosis than in the healthy volunteers (1.76 (0.51) v 1.37 (0.45) pg/ml, p < 0.05) and they correlated with the mean left atrial pressure (r = 0.74, p < 0.01). Balloon dilatation of the mitral valve reduced the mean left atrial pressure without changing the mean right atrial pressure, systemic arterial pressure, heart rate, or cardiac index. Concentrations of plasma endothelin in the femoral vein increased from 1.76 (0.51) to 3.39 (2.46) (p < 0.01), 4.82 (2.34) (p < 0.001), and 2.43 (0.52) pg/ml (p < 0.05) at 15 and 30 minutes and 24 hours after the procedure. The concentration of endothelin in the pulmonary artery also increased from 1.85 (0.85) to 4.32 (1.58) pg/ml (p < 0.01) 30 minutes after the dilatation, whereas there were no appreciable changes in endothelin concentration in the left atrium or ascending aorta. CONCLUSIONS: Plasma endothelin concentrations were higher in patients with mitral stenosis than in healthy volunteers and the increase was proportional to left atrial pressure. After balloon dilatation of the mitral valve there was an abrupt rise in endothelin in the femoral vein and pulmonary artery but no change in left atrial or aortic blood samples. These findings suggest that endothelin may be another vasoactive substance involved in congestive heart failure. PMID- 8489865 TI - Shortened left ventricular filling time in dilated cardiomyopathy: additional effects on heart rate variability? AB - OBJECTIVE: To assess possible mechanical influences underlying the reduced heart rate variability in patients with dilated cardiomyopathy. DESIGN: Comparison of standard non-spectral indices of heart rate variability with echocardiographic Doppler measures of left ventricular function in patients and normal controls. PATIENTS: 20 patients with dilated cardiomyopathy and 15 normal subjects of similar ages were studied. METHODS: Standard non-spectral indices of heart rate variability were measured over 24 hours. These were correlated with left ventricular cavity size, shortening fraction, and isovolumic relaxation time measured by M mode echocardiography, and the duration of functional mitral regurgitation and left ventricular filling time assessed by continuous wave Doppler. RESULTS: Mean RR interval and estimates of short term variability (root mean square difference of successive RR intervals, proportion of adjacent RR intervals > 50 ms different, and SD indices) were not different from normal. The overall mean (SD) of the RR interval (65 (35)), and SD of five minute mean RR intervals (55 (30)), however, were reduced compared with normal values (115 (40) and 105 (45); p < 0.01 for both). Neither correlated with left ventricular cavity size or shortening fraction, but both were strongly related to left ventricular filling time (coefficient of variation, r = 0.82 and r = 0.81 respectively). Correlation persisted when the SD was corrected for RR interval (r = 0.69) although this correlation was not found in the controls. In individual patients, the difference between RR interval at the time of echo and minimum value during the 24 hours, a measure of ability to increase heart rate, also correlated closely with filling time (r = 0.92). CONCLUSION: As the duration of functional mitral regurgitation is effectively fixed, its presence can limit the time available for left ventricular filling in dilated cardiomyopathy when heart rate is high. This may become the mechanism by which maximum heart rate is set, becoming fixed to optimise cardiac output. This manifestation of dilated cardiomyopathy may be an important factor in reduction of heart rate variability in these patients. PMID- 8489866 TI - Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. AB - OBJECTIVE: To determine the relations of plasma fibrinogen to family history of premature heart disease, personal history of hypertension, diabetes, stroke, coronary heart disease, and to presence of intermittent claudication. DESIGN: Random population survey across 22 local government districts in Scotland. PARTICIPANTS: 10,359 men and women aged 40 to 59 years. Plasma fibrinogen was measured in 8824. MAIN OUTCOME MEASURE: Plasma fibrinogen concentration. RESULTS: Persons with a family history of heart disease or a personal history of high blood pressure, diabetes, stroke, or presence of intermittent claudication all had higher plasma fibrinogen concentrations than those without. When compared with participants without cardiovascular or related disease (men: 2.27 (SE = 0.01) g/l, n = 3367; women 2.34 (0.01) g/l, n = 3096), predefined cases of either myocardial infarction (men: 2.51 (0.02) g/l, n = 248; women: 2.63 (0.04) g/l, n = 72) or angina (men: 2.45 (0.02) g/l, n = 394; women: 2.50 (0.02) g/l, n = 398) had significantly higher plasma fibrinogen concentrations (p < 0.001). After adjustment for 10 other coronary risk factors, there was a noticeable linear trend in the odds ratios for myocardial infarction across all quartiles (quarters) of plasma fibrinogen concentrations in both sexes. Similarly, the risk of angina increased linearly with increasing fibrinogen concentrations, although the test for a linear trend was NS among women. CONCLUSIONS: This large population study confirms that plasma fibrinogen is not only a risk factor for coronary heart disease and stroke, but it is also raised with family history of premature heart disease and with personal history of hypertension, diabetes, and presence of intermittent claudication. PMID- 8489867 TI - Radiofrequency-assisted "reconstruction" of the right ventricular outflow tract in muscular pulmonary atresia with ventricular septal defect. AB - A case of pulmonary atresia with ventricular septal defect is reported in which a communication was established between the right ventricle and the hypoplastic pulmonary artery by intervention, despite muscular atresia of the right ventricular outflow tract. The atresia was perforated with a special designed radiofrequency catheter (Osypka). After the creation of a canal within the muscular atresia, balloon dilatation (diameters 2, 3.5, and 7.2 mm) was performed. Arterial oxygen saturation increased from 64% to 78%. Lateral deviation of the radiofrequency catheter resulting in a lateral perforation of the atretic muscular infundibulum was well tolerated without later sequelae. Early restenosis within two weeks necessitated the implantation of a stent within the "recanalised" atresia resulting in an increased anterograde flow to the pulmonary artery. This case shows that "recanalisation" of muscular atresia of the pulmonary artery by radiofrequency is a promising technique. Additionally, stent implantation into the infundibulum to prevent restenosis is a first step to interventional right ventricular outflow tract reconstruction. PMID- 8489868 TI - Radiofrequency-assisted balloon dilatation in patients with pulmonary valve atresia and an intact ventricular septum. AB - OBJECTIVE: To investigate the efficacy and safety of transcatheter radiofrequency assisted valve dilatation for infants with pulmonary valve atresia and intact ventricular septum as an alternative to the use of laser heated wires. DESIGN: Prospective clinical study. SETTING: Three paediatric cardiology centres. PATIENTS: Four children (aged 5-101 days, weight 2.8 kg) with pulmonary valve atresia and intact ventricular septum underwent percutaneous radiofrequency assisted valve dilatation. METHODS: After delineating the atretic valve by angiography, 0.020 inch or 0.018 inch radiofrequency wires were used to perforate the atretic valve. The valve was then dilated with conventional balloon dilatation catheters up to the valve annulus diameter. RESULTS: In all four cases the radiofrequency wire perforated the atretic pulmonary valve and balloon dilatation was successful. In one patient the radiofrequency wire also passed through the anterior wall of the pulmonary artery causing tamponade which required surgical repair shortly afterwards. This patient died from sepsis six days later. One patient died three weeks after the procedure from septicaemia and a paradoxical coronary embolus. Two patients were discharged after 4 and 14 days respectively. CONCLUSIONS: Radiofrequency-assisted valve dilatation is a promising alternative to the recently developed laser wire technique. The major advantages are a reduction in cost and improved safety for the staff performing the procedure. PMID- 8489869 TI - Evaluation of anatomical obstruction by Doppler echocardiography and magnetic resonance imaging in patients with coarctation of the aorta. AB - OBJECTIVE: To evaluate a new Doppler echocardiographic index of obstruction in patients with native coarctation or recoarctation. PATIENTS: 32 patients (mean age 20, range 3 months--50 years). METHODS: Magnetic resonance imaging (MRI) was used to investigate the descending aorta. The cross sectional area of the obstruction was compared with the area of the abdominal aorta as an index of obstruction (CoA index). Doppler echocardiography was used to record the velocities in the coarctation jet and in the abdominal aorta. According to the continuity equation the ratio of these velocities should equal the ratios of the cross sectional areas. The gradients and diastolic half time of the Doppler curve were calculated. RESULTS: There was a close correlation between the MRI index of obstruction and the Doppler velocity ratio (r = 0.92). The sensitivity and specificity of this ratio in detecting a CoA index equal to or less than 0.25 were better than those obtained with gradients only or the combination of gradients and diastolic half time. CONCLUSION: The new Doppler velocity ratio correlated closely with an anatomical index of obstruction. It was easy to record in most patients and it avoided difficulties about the choice of instantaneous or peak to peak gradients and whether or not to subtract proximal velocities for the calculation of gradients. PMID- 8489870 TI - Monophasic action potentials in a patient with multiform ventricular tachycardia without QT prolongation. AB - A 41 year old woman had multiform ventricular tachycardia without QT prolongation. Monophasic action potentials were recorded from the right ventricle during the attacks of multiform ventricular tachycardia and effective refractory periods were examined at the same sites. There was no abnormal hump to suggest early afterdepolarisation in the monophasic action potentials, but there was dispersion of the effective refractory period in the right ventricle (80 ms). Stimulation from the right ventricular apex, where the effective refractory period was shortest, reproducibly induced multiform ventricular tachycardia. Two weeks after admission, when her condition was stable, multiform ventricular tachycardia could not be induced and the dispersion of the effective refractory period in the right ventricle was 20 ms. PMID- 8489871 TI - Post-exertion dizziness as the sole presenting symptom of autonomic failure. AB - An otherwise fit young man, leading an active life, whose only complaint at presentation was dizziness after extreme exertion is described. He was found later to have postural and exercise induced hypotension. Subsequently, he developed typical symptoms of autonomic failure, with postural dizziness, urinary abnormalities, and erectile failure. Progression of autonomic failure was documented on testing. A fall in blood pressure during or after exercise has been reported previously in pure autonomic failure, but a presentation with exercise induced symptoms alone is unusual. PMID- 8489872 TI - Occlusion of coronary vein grafts secondary to non-penetrating chest injury. AB - Eighteen months after graft surgery to the posterior descending, circumflex, and left anterior descending coronary arteries, it seems that blunt chest trauma caused by a car accident resulted in occlusion of the grafts. PMID- 8489873 TI - Vasospastic angina induced by prostaglandin F2 alpha. AB - A 56 year old woman underwent cholecystectomy. Postoperative paralytic ileus was treated with an intravenous infusion of prostaglandin F2 alpha. During infusion she complained of oppressive chest pain. This was accompanied by ST segment depression, and was relieved by sublingual glyceryl trinitrate. Coronary arteriography did not show significant stenosis, but subsequent intravenous infusion of prostaglandin F2 alpha provoked multiple segmental spasm of both the right and left coronary arteries. PMID- 8489874 TI - Rupture of left ventricle after mitral valve repair: case report and new technique of repair. AB - Type 1 rupture of the left ventricle occurred during mitral valve repair. A repair operation, in which the posterior leaflet of the mitral valve was used as a buttress, was successful. PMID- 8489875 TI - Current perspectives on prosthetic heart valves and valve repair. AB - The quest for the ideal cardiac valve substitute represents a highly categorized goal for the cardiac surgical community. Ongoing research has resulted in the development and creation of multiple newer heart valves and techniques for valve repair. Each of the many valves commercially available possesses a wide array of features. With the expansion of research investigations, improvement in long-term management can be translated and incorporated directly into patient care. As valvular replacement and repair/reconstruction surgery become more commonplace, it is paramount for nurses to be knowledgeable regarding the critical components of care. PMID- 8489876 TI - Hypothermia and rewarming after cardiac surgery. AB - Ensuring adequate oxygen delivery to the tissues with respect to oxygen demand is an important operative challenge during cardiac surgery. The state of the art in myocardial preservation in the 1990s has evolved to include pretreatment of the myocardium; intraoperative use of systemic hypothermia with cardiopulmonary bypass (CPB), topical cooling of the myocardium, cold cardioplegia, and myocardial reperfusion; and postoperative oxygen transport support. These techniques optimize myocardial preservation while providing adequate cardiac surgery operative times by decreasing the myocardial ischemic period, decreasing cellular metabolic requirements, and preserving energy stores. Awareness of the physiologic consequences of hypothermia in the postoperative cardiac patient improves nursing assessment of the hypothermic patient. Appropriate temperature monitoring and reporting support timely medical and nursing interventions for hypothermia, such as internal and external rewarming techniques or drug administration to facilitate the rewarming process and suppress or treat shivering. This article addresses the physiologic condition of hypothermia, the elective hypothermia techniques used during cardiac surgery, and the medical or nursing rewarming and management techniques for the postoperative cardiac surgery patient. PMID- 8489877 TI - Myocardial depression after cardiac surgery: pharmacologic and mechanical support. AB - Cardiovascular surgery patients may experience a low cardiac output state as a result of anesthesia, cardiopulmonary bypass, and myocardial stunning. Prompt assessment and early intervention are critical to patient survival. A variety of pharmacologic agents are available to support the failing circulation, including several promising new experimental inotropic agents. Intraaortic balloon pumps (IABP) and ventricular assist devices (VAD) are additional therapies reserved for advanced cardiac decompensation that is unresponsive to pharmacologic treatment. A review of etiologic factors precipitating postcardiotomy failure is presented, and traditional and experimental inotropic agents are discussed. An overview of mechanical cardiac support with the IABP, centrifugal and pneumatic VAD, and the Hemopump (Johnson & Johnson Interventional Systems, New Brunswick, NJ) device is presented, all of which addresses information critical to optimal patient outcomes. PMID- 8489878 TI - Managing low cardiac output states: maintaining volume after cardiac surgery. AB - Low cardiac output after cardiac surgery may be caused by hypovolemia, myocardial depression, vasoconstriction, and dysrhythmias. Postoperative hypovolemia occurs because of blood volume loss and decreased diastolic filling. Diuresis, intravascular fluid shift into the interstitium, hormonal influences, and bleeding deplete blood volume. Diastolic filling may be compromised by positive end-expiratory pressure, vasodilation, dysrhythmias, and venous return obstruction. The primary indicator of intravascular volume is ventricular preload, which may be measured indirectly with central venous pressure, left atrial pressure, or pulmonary capillary wedge pressure. Recognition of hypovolemia is aided through the use of cardiac pressure trend monitoring and evaluation of noninvasive indicators of hypovolemia. Nursing goals, in response to hypovolemia, are to increase the circulating volume, optimize oxygen delivery, stabilize hemodynamics, improve tissue perfusion, and prevent shock. PMID- 8489879 TI - Quality of life after cardiac surgery. AB - Tremendous strides have been made in the surgical treatment of cardiac disease. Research has documented many physical and psychologic benefits for the patient, but many questions remain unanswered. The change in quality of life may be the single most important outcome of cardiac surgery. This issue has received considerable attention in professional literature in recent years, particularly in the midst of rapidly expanding technology and soaring health care costs. This article reviews the literature related to the quality of life of cardiac surgical patients. Specific topics, such as physiologic and psychologic outcomes, return to work, family responses, and issues related to transplant patients, are discussed. The article includes a discussion of nursing implications. PMID- 8489880 TI - Care of infants with hypoplastic left heart syndrome. AB - Hypoplastic left heart syndrome (HLHS) is a common congenital heart defect that is universally fatal without surgical intervention. Two distinctly different surgical options, heart transplantation and reconstruction surgery, have been successful in treating infants with HLHS. This article reviews the anatomy and pathophysiology of HLHS. Preoperative care of infants with HLHS is discussed. The care required by infants with HLHS after heart transplantation is the same as that required by other infants who need heart transplant and has been reported. The primary focus of this report is postoperative care after staged reconstructive surgery for infants with HLHS. PMID- 8489881 TI - The economics of cardiac surgery. AB - The coronary artery bypass graft (CABG) is the most costly single surgical procedure in the United States, making bypass surgery a key target for cost containment in the current health care reform environment. This article highlights the relationship between risk factors and costs and describes some of the current initiatives aimed at cost containment and quality enhancement. PMID- 8489882 TI - Management of acute burns and burn shock resuscitation. AB - Initial management of minor and moderate, uncomplicated burn injury focuses on wound management and patient comfort. Initial management of patients with major burn injury requires airway support, fluid resuscitation for burn shock, treatment for associated trauma and preexisting medical conditions, management of adynamic ileus, and initial wound treatment. Fluid resuscitation, based on assessment of the extent and depth of burn injury, requires administration of intravenous fluids using resuscitation formula guidelines for the initial 24 hours after injury. Inhalation injury complicates flame burns and increases morbidity and mortality. Electrical injury places patients at risk for cardiac arrest, metabolic acidosis, and myoglobinuria. Circumferential full-thickness burns to extremities compromise circulation and require escharotomy or fasciotomy. Circumferential torso burns compromise air exchange and cardiac return. Loss of skin function places patients at risk for hypothermia, fluid and electrolyte imbalances, and systemic sepsis. The first 24 hours after burn injury require aggressive medical management to assure survival and minimize complications. PMID- 8489883 TI - Inhalation injury. AB - Inhalation injury remains a primary determinant of patient survival, with 60% to 70% of burn center fatalities attributed to the pulmonary complications of inhalation injury. Substantial airway damage and pulmonary complications can result from the inhalation of toxic fumes and gases found in smoke. Partial to complete airway obstruction, pulmonary edema, pneumonia, and progressive pulmonary failure may occur. Early diagnosis of inhalation injury and vigorous pulmonary care and support are vitally important to patient survival. Bronchoscopy and xenon 133 ventilation-perfusion scans are two of the newer diagnostic tools used to identify burn patients with inhalation injury. Treatment measures for patients with inhalation injury and recommendations for nursing practice are discussed. PMID- 8489884 TI - Burn wound management. AB - Management of a burn wound is interrelated with many patient care protocols. After the patient has received initial care, is in stable condition, and has been transported to the appropriate medical facility, the selection of burn wound treatment protocols is based on patient population. Hydrotherapy, debridement, topical antimicrobial agents, and dressings reduce bacterial colonization until the wound closes. Supportive care is essential to the preservation of viable tissue. Excision and autografting are the primary method of wound management. The practical application of cultured autograft and growth factors is under study. PMID- 8489885 TI - Burn care. Metabolic alterations and nutritional management. AB - Major burn trauma is one of the greatest insults the body can sustain. Complex responses to this injury greatly increase the body's energy and nutritional requirements. This article presents the metabolic responses and associated nutritional requirements that occur with a thermal injury. Nursing standards of care for the nutritional management of the patient with thermal injury are presented, since nurses have a primary role in managing the patient's care in a manner that will provide adequate nutrients, reduce energy demands, and prevent potential complications associated with the injury, healing process, and therapeutic interventions. PMID- 8489886 TI - Immune consequences of burn injury. AB - The purpose of the immune system is to protect cells from invasion by microorganisms. The body has three equally important interactive immune defense systems, all of which are profoundly disrupted with major burn injury. The immune response to burn injury is immediate, prolonged, and severe. The end result in individuals surviving burn shock is immunosuppression, with increased susceptibility to potentially fatal systemic burn wound or pulmonary sepsis. Nursing actions to support the humoral and cell-mediated immune system of the burned patient include providing nutritional support to maintain serum protein levels at optimal levels; measures to decrease edema and promote angiogenesis in areas of partial-thickness injury; meticulous treatment of the wound to prevent infection and promote healing; monitoring of antibiotic use; conservative use of invasive techniques, including intubation and vascular access devices; maintenance of fluid and electrolyte balance and body temperature; and energy conservation measures. PMID- 8489887 TI - Improving survival: infection control and burns. AB - In the past, survival of the thermally injured patient was greatly hindered by invasive infection that originated in the burn wound. Current treatment modalities, including early excision of the burn wound and prompt wound closure, administration of systemic antibiotics and topical antimicrobial agents, and mechanical isolation, have improved survival. However, infection and the sequelae of infection continue to be the leading causes of morbidity and mortality for the thermally injured patient. In addition, the burn patient remains highly susceptible to other infectious processes. A thorough understanding of infection control and burns are essential to the successful treatment of burn injuries. PMID- 8489888 TI - When is the burn injury healed?: psychosocial implications of care. AB - The psychosocial and economic effects of burn trauma are profound, not only for the patients, their families, and the burn unit staff members, but also for society as a whole. Understanding the perception of stresses experienced by patients, families, and staff is discussed, and related strategies to assist in reducing the stress are presented. A comprehensive psychosocial support system can assist the nurse in reducing the psychosocial morbidity of severe burn trauma. PMID- 8489889 TI - Pediatric burn injuries. AB - Care of the pediatric burn patient requires knowledge of physiologic differences between adults and children for estimation of burn size, calculation of fluid needs, and assessment of response. Dressing techniques, pain management, and nutritional and psychologic support of this population require special considerations. PMID- 8489890 TI - [Emergency or elective surgery in the treatment of acute cholecystitis]. AB - The authors report their experience in the surgical management of acute cholecystitis. From 1979 to 1991, 308 patients underwent early cholecystectomy. Results obtained, accuracy of pre- and intraoperative diagnostic investigations, and surgical strategy are discussed in relation to prognostic indexes. Personal experience and literature review indicate early cholecystectomy as the treatment of choice in acute cholecystitis. PMID- 8489891 TI - [Posttraumatic pseudoaneurysms of the anterior tibial artery: a review of the literature and a clinical case report]. AB - The authors after a review of the literature report a case of anterior tibial artery false aneurysm in a seventeen year old male, due to traumatic sprained ankle during a basketball match. Surgical techniques used in repairing the lesion as well as microsurgical technique for the direct suture of the artery, which allowed to resolve the problem, are discussed. PMID- 8489892 TI - [Echinococcal cysts with primary muscle localization: comments on a clinical case]. AB - Primary muscular localization of echinococcosis is rare and unknown are the causes that determine it. The authors report a case recently observed and illustrate the etiopathogenetic hypothesis more accredited in the literature. It is concluded that surgical treatment is the best choice, although relapses are possible. Therefore, a long term follow up of the patients including clinical and serological investigations is advisable. PMID- 8489893 TI - [Primary sarcoidosis of the breast: a clinical case]. AB - Sarcoidosis of the breast is rare and only few cases are reported in the literature. A case of sarcoidosis presenting as a breast mass with no other evidence of disease is herein reported. Ultrasound and fine needle aspiration biopsy were performed, but only excisional biopsy with microscopic examination confirmed the diagnosis. Differential diagnosis with other granulomatous lesions is important to select the proper treatment. PMID- 8489894 TI - [The pilonidal sinus: its surgical treatment, our experience and a review of the literature]. AB - The authors report their experience in the surgical management of pilonidal sinus. During a 3-year period (1989-1991) 106 patients underwent primary closure. Average postoperative stay was 5.5 days, while mean healing time was 14.6 days. During the follow up, 3 patients developed a true recurrence (3.26%). After a critical review of the literature, the authors emphasize the importance of primary closure in the surgical treatment of pilonidal disease. PMID- 8489895 TI - [Quandrantectomy in the conservative treatment of breast carcinoma]. AB - Two years after the first evaluation, the authors review the results of quadrantectomy in the conservative treatment of breast carcinoma. Local control of the disease by quadrantectomy with axillary lymphadenectomy and radiotherapy has been more difficult in the T2 patients (4 local relapses out of 41 patients) compared T1 patients (3 local relapses out of 52 patients). Nodal involvement appears to be not crucial for the prognosis (7 patients out of 10 with remote metastases were N- at the time of surgery). PMID- 8489896 TI - [A proposed clinico-instrumental protocol for diagnostic guidance in breast lumps]. AB - Women who practice self-examination of the breast often believe to identify lumps which produce much concern; in many cases differential diagnosis with cancer is therefore necessary. The authors propose a clinical-instrumental protocol as a guide to the right diagnosis in these patients. PMID- 8489897 TI - [Peritonectomy in the treatment of ovarian carcinoma at an advanced stage]. PMID- 8489898 TI - [The changes in the sexual behavior of patients undergoing aorto-iliac revascularization]. AB - A correct approach to sexual disorders in vascular patients presupposes an accurate investigation before and after operation. The authors evaluate the reliability of the diagnostic methods used, pre- and postoperatively, to ascertain sexual disorders, and analyse the influence of surgery on sexual function. PMID- 8489899 TI - [Trauma: when the liver "ruptures".... Our experience of 125 cases]. AB - Liver and spleen are the organs most frequently involved in the blunt abdominal trauma. Prognosis is severe in those cases classified as IV or V according to the More score. The imaging techniques, particularly CT scan, offer today a possibility in the nonoperative management of a selected group of haemodynamically stable patients, therefore reducing the need of surgery. The authors' experience in 125 patients observed from 1983 to 1991 is reported. PMID- 8489900 TI - [Ischemic colitis localized in the right colon. A clinical case report]. AB - Ischemic colitis shock-associated still is a not well-defined clinical entity. The authors describe symptoms, clinical course and treatment in a case recently observed. They outline the difficulties of preoperative diagnosis and the need of a not postponable surgical treatment due to shock and peritonitis. PMID- 8489901 TI - [Anterior approaches to the spinal column: considerations of the surgical technic]. AB - The anterior approach to the vertebral column is indicated in the tumors or traumas of the vertebral body with prevalent anterior expression. This method allows to control easily all the structures in front of the rachis. Furthermore, the current reconstructive techniques require the exposure of a long tract of the vertebral column. The Authors report their experience with the anterior approach in 22 patients (9 males, 13 females) affected by different pathologies: 10 primary tumors divided as follows: 4 sacral chordomas, 1 L1 chordoma, 2 sacral neurinomas, 1 L5 malignant melanotic schwannoma, 1 D9 osteoblastoma, 1 D6 intraspinal cavernoma, and 1 D3 myeloma; 4 metastatic tumors (2 D10, 1 L4 and 1 L5); 5 fractures of the vertebral body (1 L1, 1 L1-L2, 2 L4 and 1 L5); 2 echinococcal cysts respectively arising from the D11 body, the sacrum and ilium. The Authors overall performed 8 thoracotomies, 6 for dorsal location; in 1 case of L1-L2 fracture a thoracophrenolaparotomy was performed; in 7 cases involving the L3-L5 segment an abdominal anterolateral extraperitoneal approach was followed; finally in 6 cases a transperitoneal laparotomy to approach the sacrum and ilium was performed. PMID- 8489902 TI - Dracunculiasis. Global surveillance summary, 1992. PMID- 8489903 TI - The programme of undergraduate cancer education of the Lodz School of Medicine (Poland). PMID- 8489904 TI - The tumor cell biology doctoral training program at Northwestern University. PMID- 8489905 TI - The influence of undergraduate medical cancer education on students' sensitivity towards cancer. AB - Cancer is a disease that doctors will have to face for many years to come. Our Department of Surgical Oncology is particularly interested in altering undergraduate students' and junior doctors' performance with respect to cancer and cancer patients' care. We believe that a solid base of knowledge gained during the undergraduate period with appropriate guidance will equip doctors with the necessary discipline towards cancer and its prevention. Cancer education must be ongoing and supported by all specialists, since cancer is a disease requiring multidisciplinary attention. This survey was conducted to evaluate the oncologic aspects of the undergraduate curriculum of our medical school. PMID- 8489906 TI - Undergraduate medical teaching in departments of oncology in the United Kingdom: a questionnaire survey. AB - A questionnaire survey has been conducted to assess the nature and extent of teaching given to undergraduate medical students in departments of Oncology within the United Kingdom. Postal questionnaires were sent to 58 departments of Radiotherapy/Oncology and 30 departments of Medical Oncology. This included both teaching and nonteaching departments. Response rates were 84.5% (49 replies) and 90% (27 replies), respectively. Of the responders, 26 Radiotherapy/Oncology departments (53%) and 21 Medical Oncology departments (78%) have a regular commitment to undergraduate medical teaching, the majority being units affiliated to teaching hospitals. The time spent in teaching, methods of teaching, the teaching curriculum, and other details have been documented and are summarised. The information obtained leads us to conclude that there is a considerable variation between departments with regard to teaching commitments and the curriculum. Such variations appear to be primarily centre oriented rather than specialty biased. The survey also raises a number of issues regarding undergraduate medical teaching with reference to oncology, which are discussed. PMID- 8489907 TI - Elective introduction to oncology. AB - Since 1974, the St. George Medical Society, a component of the American Cancer Society's Philadelphia Division's Professional Education Program, has sponsored paid summer clinical and research fellowships for Philadelphia medical students completing their first year. Six lectures at the student level are presented throughout the year. Students run a single society, elect officers, and select site and speakers under the guidance of the St. George Medical Society Subcommittee. Faculty from six medical schools and individual faculty preceptors donate time to provide a one-on-one summer experience in medical oncology, surgical oncology, gynecologic oncology, radiation oncology, pathology, and cancer-related research in university hospitals, community hospitals, and private offices. Financial support is provided by directed donations. Currently 50 clinical fellowships are offered. Since its inception, over 750 "fellowships" have been awarded, and over 3,000 students have attended the lectures. The program successfully provides a voluntary one-on-one introduction to clinical oncology in a reproducible format. PMID- 8489908 TI - Cancer control knowledge and priorities among primary care physicians. AB - Primary care physicians can play a key role in prevention and early detection of cancer. To assess cancer control knowledge and priorities among primary care physicians in Missouri, we conducted a random survey of 207 physicians. Although reported knowledge of the role tobacco plays in cancer causation was high, activity in tobacco cessation counselling and referral was low. Respondents considered diet to be a relatively unimportant factor in cancer causation, whereas they viewed sun exposure, genetics/family history, and radiation exposure as large contributors to the cancer burden. Among cancer early detection tests, high activity was shown for the Pap test and breast examination. Conversely, low activity was reported for colon sigmoidoscopy. Inverse correlations were shown between age group of the physician and several cancer prevention and early detection practices. For each cancer prevention and screening practice, reported activity was higher for medical doctors than for doctors of osteopathic medicine. Possible barriers or controversies in cancer control included disagreement with the current recommendation for Pap testing, the cost of mammography, and patient fear of sigmoidoscopy. These findings suggest that primary care physicians are not achieving their full potential in cancer control and indicate areas where increased emphasis is warranted. PMID- 8489909 TI - Health-care professionals' use of cancer-related patient education materials: a pilot study. AB - While the American Cancer Society and National Cancer Institute expend much effort designing patient education materials, little is known about how health care professionals use such materials in everyday practice. We piloted a descriptive study of primary care providers in San Francisco. Using a standardized questionnaire, we conducted face-to-face interviews with 71 health care professionals who responded to a mailed offer of a free set of American Cancer Society (ACS) materials. Most (72%) said their patients rarely or never requested cancer information, yet most (87%) distributed some type of health education material. However, 35 (49%) did not currently use ACS materials, citing as reasons: not having access to them (97%), incorrect language for patient population served (9%), and patient illiteracy (6%). Only 6% of providers believed these materials ineffective. The 33 practitioners using ACS materials most commonly distributed breast self-examination, colorectal cancer screening, smoking cessation, and mammography information. All 71 respondents were given a display rack containing ACS materials. Most (70%) planned to place the display rack in their office waiting room; few planned to place it in their examination room (13%) or adjacent hallway (10%). One-third (32%) of providers planned simply to let their patients browse through the materials, and only 7% planned to hand materials to patients directly. Future studies should focus on how such materials can be more efficiently distributed and more effectively used. PMID- 8489910 TI - Psychological distress in cancer patients and their spouses. AB - The degree of psychosocial distress experienced by 15 cancer patients with newly diagnosed metastatic disease and their spouses was investigated. Of interest were mean changes over the six-month interval following diagnosis, and correlations between partners at 0, 3, and 6-7 months. The Psychosocial Adjustment to Illness Scale (PAIS) and the Family Environment Scale (FES) were used to quantify adjustment. Several PAIS subscales exhibited increasing distress over time for patients: Social Environment (p = 0.004), Vocational Environment (p = 0.028), and Psychological Distress (p = 0.029). FES Conflict increased over time (p < 0.005), while Intellectual Cultural Orientation declined (p = 0.02), both for spouses only. Of 24 patient-spouse PAIS correlations (7 subscales plus a global scale, at three times), 7 (29%) were 0.70 or greater (ps < 0.01). Of 30 FES correlations, 17 (57%) were 0.7 or higher (ps < 0.01). These results suggest that some stresses increase over time, and that spouses and patients share a similar perceived level of distress. Health professionals must address the psychological distress of the spouse as well as the patient. PMID- 8489911 TI - Gender differences in perceptions of cancer. AB - The purpose of this study was to consider gender differences in laypeople's beliefs about and explanations of cancer. Over 700 adults answered a questionnaire about their perceptions and explanations of the disease. The majority of respondents identified cancer as the most fearful disease. Women were more frightened of cancer than were men, whereas men were more frightened of heart disease than were women. The greatest fear of cancer was its perceived incurability and the associated suffering, whereas the greatest fear of heart disease was perceived susceptibility. Men were more likely than women to hold a more negative attitude toward cancer information. Factor analysis of the perceived causes of cancer identified four causal factors, which were labelled Stress, Environmental, Health-related, and Behavioural. Men were more likely to identify behavioural items as important whereas women were more likely to rate heredity as important. Fear of cancer was highly correlated with the health beliefs but not with the perceived causes of cancer. However, a regression analysis found that these health beliefs explained only a small proportion of the variance in cancer fear. The findings are discussed with reference to cancer education. PMID- 8489912 TI - Nutritional concerns of women with breast cancer. AB - Health professionals should assess the nutrition information needs of women with breast cancer in order to provide appropriate services. Questionnaires were mailed to 143 Reach to Recovery volunteers who had had surgery for breast cancer, and 72% responded. The subjects were mostly concerned about and wanted information on diets for cancer prevention, low-fat diets, weight reduction, and vitamin supplements. Findings also showed the potential for excessive vitamin/mineral use among one-third of respondents and a tendency toward weight gain regardless of whether or not chemotherapy was received. The results provide direction for development of nutrition educational materials and programs for women with breast cancer. PMID- 8489913 TI - The training of a member of the multidisciplinary cancer teaching team. PMID- 8489914 TI - A strategy for evaluating a novel smoking intervention device. AB - The Victorian Smoking and Health Program (VSHP) was established in 1985 to (1) determine the views of smokers making a quit attempt regarding the acceptability and usefulness of a novel self-help smoking cessation device (the QUITZ pack), (2) define a potential market by determining the correlates of use of the QUITZ pack, and to (3) determine how the QUITZ pack compared to existing resources with proven acceptability and usefulness. Telephone interviews were conducted of 120 smokers who rang the QUITZ office for resources to help in a quit attempt. The results showed that most people found the QUITZ pack to be acceptable, both on first receiving it (68% acceptable) and after they had had the resource for at least a week (61% acceptable). The QUITZ pack was used in some way by 58% of the people to whom it was sent. No significant associations were found between the use of the pack and any of the demographic, smoking history, or motivational factors examined. Around a third of smokers to whom it was sent rated the QUITZ pack as being either quite or very useful in their cessation attempt. Of those who reported using the QUITZ pack, 61% rated it as being quite or very useful. For those who used the pack and made a quit attempt, more respondents rated a self-help guide (the CanQuit book) (87%) and any other personally chosen strategy (87%) as being quite or very useful, than rated any components of the QUITZ pack in this way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8489915 TI - Evaluation of an electronic message strip to recruit smokers to a smoking cessation program. AB - Knowledge of outcome is essential when analyzing effectiveness of educational programs. Although quantitative data can be analyzed more rigorously than other forms of data, quantitation of behavioral processes is often difficult. To promote our smoking-cessation program we designed a method that relies on electronic message strips and a dedicated telephone line capable of providing quantitative outcome information. This approach appears quite versatile and shows that the electronic message strip is a surprisingly ineffective method of enlisting subjects into a smoking-cessation program in our hospital. PMID- 8489916 TI - Education in radiotherapy in Poland. PMID- 8489917 TI - Staff support: a family loss. Interview by Charlotte Alderman. PMID- 8489918 TI - Expedition medicine: a trip into the unknown. PMID- 8489919 TI - Nurses work. Nursing in continents. PMID- 8489920 TI - Nurses work. Katie's quest continues. PMID- 8489921 TI - Lifting patients: the challenge for nursing. AB - This article examines how nursing will need to respond to the guidelines included in the new Health and Safety Regulations on the minimum requirements for the handling of loads. Many lifts that nurses undertake are called into question and the author outlines where nurses may be at risk and suggests alternative methods to lifting. The article also looks at what can go wrong when decisions about lifting miss out key points related to lifting stance and sequence. PMID- 8489922 TI - Patients' views of their A&E experience. AB - The concluding article in this series will explore the patients' perspective of their A&E experience through the use of evaluative questionnaires. Developments in quality assurance and the impetus from the Patient's Charter have led to staff being more concerned with patients' evaluation of their experiences, and A&E is no exception. The study revealed that patients are poor predictors of their treatment but the majority are satisfied with their experience. A smaller study of patients who walked out before treatment showed that a third did not seek subsequent help. The author argues that the study supports the need for nurse triage and nurse practitioners. PMID- 8489923 TI - Nutritional problems in nursing homes (continuing education credit). AB - This article examines the incidence of clinical malnutrition among nursing home residents and comments on the relevance of the COMA report on dietary reference values (1) to elderly people. The author discusses the medical, social and economic causes of malnutrition and postulates that the gap between rich and poor, which has widened in the last decade, has increased the proportion of elderly people nutritionally at risk. She highlights the vulnerability of nursing home residents, calls for further research and makes key recommendations to improve current practice. PMID- 8489924 TI - Cardiac pacing: a clinical update. AB - The aim of this article is to review the current technology, clinical indications and implantation methods of cardiac pacemakers. The author describes the implantation procedure, and outlines appropriate pre and post-procedural care. Despite the complexity of the subject, cardiac pacing is a life-preserving procedure for many patients, and is one that nurses should understand. PMID- 8489925 TI - Media coverage about health care workers with AIDS. PMID- 8489926 TI - Purely academic? PMID- 8489927 TI - Enrolled over and died. PMID- 8489928 TI - Don't tell the patient. PMID- 8489929 TI - Private's progress. PMID- 8489930 TI - EuroQuan. Finnish first. PMID- 8489931 TI - EuroQuan. Quality questions. PMID- 8489932 TI - EuroQuan. The RCN ODySSSy project. PMID- 8489933 TI - EuroQuan. Setting up a network. PMID- 8489934 TI - EuroQuan. Quality in Europe. PMID- 8489935 TI - [Childhood anemias]. PMID- 8489936 TI - [Hematopoietic growth factors]. PMID- 8489937 TI - [Prenatal diagnosis and therapy of Rh-erythroblastosis]. PMID- 8489938 TI - [Blood transfusions]. PMID- 8489939 TI - [Thrombocytopenias and granulocytopenias]. PMID- 8489940 TI - [Acute leukemia in children]. PMID- 8489941 TI - [Handling cytostatic drugs]. PMID- 8489942 TI - [Everyday life at the oncological pediatric department at the Freiburg Oncological Pediatric University Hospital]. PMID- 8489943 TI - [Why do we need therapy studies?]. PMID- 8489944 TI - [Special nursing measures in oncology departments]. PMID- 8489945 TI - [Bone tumors in children]. PMID- 8489946 TI - [Prosthetic measures in bone tumors]. PMID- 8489947 TI - [Radiotherapy in pediatric oncology]. PMID- 8489948 TI - [Preparation for radiotherapy, a task for the psychosocial team]. PMID- 8489949 TI - [Bone marrow transplantation in children]. PMID- 8489950 TI - [Role of the nursing personnel in the pediatric-oncologic team]. PMID- 8489951 TI - [Dealing with relapsed patients--from the physician's point of view]. PMID- 8489952 TI - [Dealing with relapsed patients--from the psychiatric therapist's viewpoint]. PMID- 8489953 TI - [Dealing with relapsed patients--from the viewpoint of the nursing personnel]. PMID- 8489954 TI - [First Aid for children by the Emergency Service. Possibilities and limitations]. PMID- 8489955 TI - [Phimosis and balanitis--guidelines for care]. PMID- 8489956 TI - [Short-term patient education for type I diabetics in the hospital--experiences in a pediatric department]. PMID- 8489957 TI - ["Mischka-Russia-Childrens Aid Association"--an initiative helping disabled and sick children in Moscow]. PMID- 8489958 TI - [New earthlings--and their parents]. PMID- 8489959 TI - [Microwave heating of baby milk bottles]. PMID- 8489960 TI - [Henri-Louis Roger (1809-1891)]. PMID- 8489961 TI - [Obligation to inform prior to blood transfusions--this obligation includes information on the risk of hepatitis and AIDS infection due to homologous transfusion]. PMID- 8489962 TI - [Vitamin K--preventive administration in the newborn]. PMID- 8489963 TI - [Blood counts and their dependency on the patient's age]. PMID- 8489964 TI - The role of hormonal and dietary factors in pancreatic carcinogenesis. AB - The pancreatic cancer continues to represent an important problem, as a cancer with extremely poor prognosis. To date more than 16 chemicals have been shown to induce pancreatic tumors, in animal models. The tumors developed in rats are essentially of acinar type and those in hamsters mostly of ductal type. Many studies proved the direct or indirect role of hormonal and dietary factors in pancreatic cancer. The development of alternative treatments according to biological and biochemical steps of carcinogenesis is available as adjuvant treatment. We present herein an overview of current experimental and clinical results in order to understand the evolution, histogenesis and biological behaviour of pancreatic cancer. PMID- 8489965 TI - Reticuloendothelial system function following acute liver failure induced by 90% hepatectomy in the rat. AB - Sepsis and bacterial infections are frequent complications of acute liver failure and following major liver resection. The mechanisms underlying this phenomenon are unclear. In this study, RES function and blood clearance of radiolabelled E. coli was immediately impaired following 90% hepatectomy, although the reduction in liver volume resulted in an increase in splenic (temporary) and pulmonary (persisting) uptake. A significant correlation between liver function and host RES function was observed. The uptake capacity of the RES in the liver remnant and spleen did not correlate with subserosal blood flow. The uptake in the brain gradually increased with time, paralleling an increased leakage across the blood brain barrier. Thus, a significantly impaired RES function resulted from experimental 90% hepatectomy-induced acute liver failure, which might explain the high incidence of septic events in the clinical situation. PMID- 8489966 TI - Injuries of the portal vein in patients with blunt abdominal trauma. AB - Between January 1987 and September 1991, 68 severely traumatized patients underwent emergency laparotomy because of blunt abdominal trauma. Intraoperatively, 54.4% of the patients had a major injury to one organ, 23.5% had injuries to two organs, 16.2% had injuries to three organs and 5.9% to four or more organs. Additionally, in 11.8% of these cases (n = 8) a major vascular injury (portal vein n = 5, vena cava n = 2, mesenteric root n = 1) was found. Injuries to the portal vein were always associated with complete rupture of the pancreas, requiring distal pancreatic resection in four cases and a duodenum preserving resection of the head of the pancreas in one. In two of these patients the portal vein had to be reconstructed with a Goretex prosthetic graft. Mortality was 14.7% for the whole group (n = 68) and 0% for patients with additional portal venous injuries. PMID- 8489967 TI - Ultrasonic mucosectomy of the gallbladder. A histological analysis. AB - The Cavitron Ultrasonic Surgical Aspirator (CUSA) may be used to remove mucosa of organs of the gastro-intestinal tract. A histological analysis was performed on gallbladders treated with a CUSA-mucosectomy to assess the extent and degree of mucosectomy and to evaluate parietal damage. The histological studies performed on three specimens of chronic cholecystitis revealed a complete mucosectomy except in areas where Rokitansky-Aschof sinuses were present. There was no evidence of parietal damage. The CUSA may be used to remove the mucosa of gallbladders without injury to other layers, and may have a potential application in procedures such as mucosal cholecystectomy. PMID- 8489968 TI - "Clip-stone" filiation within the biliary tract. AB - A case of cholangitis due to the migration of a metal clip used for surgical cholecystectomy 4 years earlier, is reported. The diagnostic approach and therapeutic options, either endoscopic or surgical are discussed. The use of resorbable clips during the performance of laparoscopic cholecystectomy should avoid this type of complication. PMID- 8489969 TI - Papillo-choledochectomy in the operative management of mucosal neoplasms of the periampullary region. AB - Two patients with mucosal cancer of the periampullary region were treated with papillo-choledochectomy, which entails removal of the papilla of Vater and the whole length of the common bile duct. The neoplasm is dissected out through the plane between the duodenal circular and longitudinal muscles, deep to the sphincter of Oddi and the fibromuscular layer of the bile duct. Pathological examination showed that cancer was confined to the mucosal layer without stromal invasion, and that the operation achieved radical cure. For mucosal cancer, papillo-choledochectomy is an alternative to pancreatoduodenectomy, provided that repeated frozen-section studies confirm the completeness of excision. PMID- 8489970 TI - Extrahepatic biliary papillomatosis occurring after removal of a dysplastic gall bladder. AB - A case is presented of a woman who developed obstructive jaundice secondary to dysplastic mucinous papillomatosis two years after she had undergone cholecystectomy and exploration of the common bile duct. The gall bladder was dysplastic. It is suggested that the dysplastic glands removed from the common bile duct at the second operation either represented seedlings from dysplastic areas of the gall bladder or were a manifestation of dysplastic field change. PMID- 8489971 TI - Cholangitis and Budd Chiari syndrome as complications of simple cystic liver disease. AB - We report the case of a 63 year old woman who developed the complications of cholangitis and Budd Chiari syndrome secondary to polycystic disease of the liver. The two complications were not present simultaneously, and both resolved after decompression of the liver cysts. PMID- 8489972 TI - Splenic vein obstruction due to a solitary echinococcal splenic cyst, resulting in gastric fundus varices: an unusual cause of variceal bleeding. AB - A 27-year old female patient, born and living in Morocco, suffered from severe variceal bleeding and weight loss. Eventually a diagnosis of gastric fundus varices was made supposedly resulting from partial obstruction of the splenic vein and collateral blood flow via the short gastric veins. Splenectomy was proposed. Peroperatively it became apparent that a solitary ecchinococcal cyst in the hilus of the spleen obstructed the blood flow in the splenic vein. The cyst, the spleen, and part of the pancreatic tail were removed. After splenectomy bleeding did not recur. PMID- 8489973 TI - Large foreign body as a nidus for a common duct stone in a patient without spontaneous biliary enteric fistula or previous abdominal surgery. AB - We report a case of a brown pigment gallstone, which formed around a phytobezoar in the common bile duct, in a patient without spontaneous biliary enteric fistula or previous abdominal surgery. A brief comment on the possible origin of the phytobezoar in this case and on the pattern of deposition of brown material over a pre-existent nidus is also presented. PMID- 8489974 TI - Effect of speed of injection on the maximum sensory level for spinal anesthesia using plain bupivacaine 0.5% at room temperature. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate if a ten-fold difference in speed of injection of a plain solution of bupivacaine 0.5% at room temperature into the subarachnoid space would result in a temperature-dependent change in baricity large enough to be reflected in a significant difference between the maximum levels of sensory blockade. METHODS: In this prospective study, 40 male patients were randomly assigned to one of two groups. Group 1 patients received 3 ml plain bupivacaine 0.5% (20-22 degrees C) with the speed of injection as fast as possible. Group 2 patients received 3 ml plain bupivacaine 0.5% (20-22 degrees C) at a rate of 0.05 ml/sec. Thirty minutes after subarachnoid injection the maximum level of sensory blockade was determined by pinprick in the anterior axillary line by a blinded observer. RESULTS: The mean maximum level of sensory blockade in patients of group 1 was T7.5 (median, T7; range, T3-12) and in group 2 patients T6.4 (median, 5.5; range, T3-11), the difference not being statistically significant (p > 0.05). CONCLUSIONS: There is no clinically relevant influence on the maximum level of sensory blockade when bupivacaine 0.5% at room temperature is injected with a ten-fold difference in speed. PMID- 8489975 TI - Pulse oximeter waveforms from the finger and toe during lumbar epidural anesthesia. AB - BACKGROUND AND OBJECTIVES: To determine whether lumbar epidural anesthesia affects pulse oximeter signals in the upper or lower extremity, 13 ASA I patients were studied. METHODS: Temperature and pulse oximeter probes were placed on the finger and the toe. RESULTS: After epidural injection, the amplitude of the pulse oximeter waveform on the toe increased eight-fold but declined by 50% in the finger. The increase in amplitude of the pulse oximeter waveform in the foot preceded the temperature rise. CONCLUSIONS: More reliable pulse oximeter signals may be obtained from the toe than the finger during lumbar epidural anesthesia. Furthermore, the increase in the pulse amplitude from the toe may aid in the early detection of successful epidural block. PMID- 8489976 TI - Prolonged placement of spinal catheters does not prevent postdural puncture headache. AB - OBJECTIVE: To determine whether leaving an intrathecal catheter in place in the postoperative period prevents postdural puncture headache (PDPH). METHODS: Lumbar puncture was performed with an 18-gauge Tuohy needle. 0.5% bupivacaine spinal anesthesia was given through a 20-gauge catheter in 87 patients having orthopedic surgery. Postoperatively, patients were allocated randomly to have the catheter immediately withdrawn (group 1, N = 47) or kept in place for 12 to 24 hours (group 2, N = 40). Patients were questioned by a blinded observer, about PDPH twice a day on postoperative days 1, 2, 3, and 8. RESULTS: The incidence of PDPH was 9.2%, and this was comparable in the two groups (5 patients in group 1 and 3 patients in group 2). CONCLUSION: Leaving the intrathecal catheter in place in the postoperative period for 12 to 24 hours does not prevent PDPH. PMID- 8489977 TI - The characteristics of analgesic requirements following subarachnoid diamorphine in patients undergoing total hip replacement. AB - BACKGROUND AND OBJECTIVES: The postoperative pain scores and analgesic requirements were assessed in 60 patients who had undergone total hip replacement under bupivacaine spinal anesthesia. METHODS: Thirty of the patients had intrathecal diamorphine injected after the bupivacaine, and the remaining 30 received saline. RESULTS: Superior postoperative pain relief was obtained in the diamorphine group, whose average postoperative morphine requirements were 12 +/- 11.4 mg compared to 31 +/- 18.7 mg (mean +/- SD) in the control group. Despite the lower doses of morphine, their pain scores over the first 24 hours postoperatively were consistently lower. No differences were seen between the groups with respect to respiratory depression, nausea, pruritus, postoperative sedation, headache, or urinary retention. CONCLUSION: Pain control after intrathecal diamorphine supplemented by intravenous morphine from a patient controlled analgesia system is superior to intravenous morphine alone. PMID- 8489978 TI - Inhibition of epidural morphine-induced pruritus by intravenous droperidol. AB - BACKGROUND AND OBJECTIVES: Our objective was to study in more detail our previous finding that intravenous droperidol inhibits pruritus induced by epidural morphine. METHODS: In a double blind study, 107 ASA I or II patients undergoing cesarean section received epidural anesthesia with 150 mg (30 ml) of 0.5% bupivacaine with 1:200,000 epinephrine and 2 mg of morphine hydrochloride in a single injection. They were randomly allocated to either receive (treated group, n = 54) or not receive (control group, n = 53) an intravenous injection of 2.5 mg of droperidol just after delivery. During the postoperative period, the patients were assessed for the occurrence and severity of pruritus or other possible untoward symptoms. Pruritus was classified as absent, mild, moderate, or severe. RESULTS: The incidence of pruritus in control group was absent, 26.4%; mild, 39.6%; moderate, 28.3%; severe, 5.7%; for the treated group, the incidences were, respectively: 59.2; 27.8; 13.0; and 0.0% (p = 0.0003; Mann-Whitney test). As for other side effects of morphine, nausea and vomiting had a similar incidence in the two groups; urinary retention could not be analyzed because of bladder catheterization, and constipation, herpes labialis and clinical evidence of respiratory depression were never observed. Droperidol produced a greater incidence of somnolence (2% in control and 17% in treated group--p < 0.02; Fisher's exact test), but it was never incapacitating. The incidence of hypotension was similar in the two groups. CONCLUSION: Intravenous droperidol reduces the incidence and severity of pruritus caused by epidural injection of morphine without inducing important side effects. PMID- 8489979 TI - Phantom limb pain. PMID- 8489980 TI - Complications during spinal anesthesia for cesarean delivery: a clinical report of one year's experience. AB - BACKGROUND AND OBJECTIVES: To evaluate the incidence and causes of complications associated with spinal anesthesia for cesarean delivery. METHODS: Prospective study, case series. SETTING: Tampere University Hospital, 284 patients scheduled for elective or nonelective cesarean delivery with spinal anesthesia. Complications occurring during spinal anesthesia with hyperbaric 0.5% bupivacaine during a 1-year period were analyzed. RESULTS: Hyperbaric 0.5% bupivacaine for cesarean delivery proved to be a reliable anesthetic with a failure rate of 2.8%. The most common complications were hypotension (42%) and nausea (14%). In 81% of patients, hypotensive periods occurred before delivery. Hypotension before delivery had no correlation with low Apgar scores or with low pH in the umbilical artery of the infant. Risk factors for hypotension were elective procedures and operations without prophylactic ephedrine infusion. Nausea occurred significantly more often if a lower interspace was used for administering the subarachnoid block. CONCLUSIONS: Spinal anesthesia proved to be a safe, reliable, and rapid method of anesthesia for cesarean delivery, but, in view of a high incidence of minor complications, careful patient monitoring during spinal anesthesia is necessary to make the outcome optimal for mother and fetus. PMID- 8489981 TI - Regional anesthesia in a patient with epidermolysis bullosa. PMID- 8489982 TI - Anesthetic management of a patient with Franklin's disease. PMID- 8489983 TI - A reliable method of testing regional block. PMID- 8489984 TI - Sphenopalatine ganglion block under vision using rigid nasal sinuscope. PMID- 8489985 TI - Transdermal clonidine: treating reflex sympathetic dystrophy. PMID- 8489986 TI - Management of postoperative pain by anesthesiologists: a time for optimism. PMID- 8489987 TI - Are anesthesia residency programs failing regional anesthesia? The past, present, and future. AB - BACKGROUND: A survey of anesthesia training programs in 1980 reported the use of a regional anesthetic technique in 21.3% of cases. Since that time, numerous changes have occurred in anesthesia residency programs. This survey was conducted to assess the impact these changes have had on the use and teaching of regional anesthetic techniques in residency training programs. METHODS: All anesthesia residency program directors were requested to send blinded copies of their residents' 1989-1990 American Board of Anesthesiology Annual Training Report Forms. Data from responding programs were compared to similar data from 1980, and analyzed for factors expected to influence the use of regional anesthesia during training. RESULTS: The use of regional anesthesia in residency training programs has increased from 21.3% in 1980 to 29.8% in 1990, primarily because of a two fold rise in the use of epidural anesthesia. The use of regional anesthesia is strongly correlated with a resident's exposure to obstetric anesthesia and pain consultations. Wide variability between residency programs remains. CONCLUSION: Some training programs continue to fail to provide adequate regional anesthesia exposure to train residents fully in these techniques, despite the overall increased use of regional anesthesia. PMID- 8489988 TI - Combined inguinal paravascular (3-in-1) and sciatic nerve blocks for lower limb surgery. AB - BACKGROUND AND OBJECTIVES: The effects of increasing the maximum recommended dose of lidocaine 1% plus epinephrine from 500-650 mg in combined 3-in-1/sciatic nerve block were investigated in 45 adult patients scheduled for surgery on the lower limb. The goal of the study was to show primarily, whether pneumatic tourniquet pain could be reduced, whether toxic plasma levels of local anesthetic were reached, and whether any other clinical side effects occurred. RESULTS: The results indicated that the incidence of tourniquet pain was significantly reduced and, most important, that there were no noteworthy differences in venous lidocaine plasma levels between the two groups investigated. CONCLUSIONS: There was a significant decrease in time required for complete neural blockade after administration of the 650 mg lidocaine dose, and little or no difference in the duration of postoperative analgesia. PMID- 8489989 TI - The effect of continuous interscalene brachial plexus block with 0.125% bupivacaine plus fentanyl on diaphragmatic motility and ventilatory function. AB - BACKGROUND AND OBJECTIVES: Continuous interscalene brachial plexus block with 0.25% bupivacaine decreases diaphragmatic motility and ventilatory function. The author studied the effects of 0.125% bupivacaine with and without fentanyl. METHODS: Forty patients who were to undergo shoulder surgery were given an interscalene brachial plexus block using 20-28 ml 0.75% bupivacaine plus epinephrine. In random order, 10 patients then had a 24-hour continuous block with 0.125% bupivacaine (BUPI) (5-9 ml/h). Nine patients had an additional s.c. infusion of fentanyl (F-SC) (15-27 micrograms/h) and 10 the same dose of fentanyl with the bupivacaine infusion (F-PLX). Ten patients had a single block (PLX) for minor surgery. Spirometry, double-exposure chest radiography, pulse oximetric hemoglobin saturation and maximal airway pressures were measured. RESULTS: Postoperatively, BUPI patients were given, on average, 1.2, F-SC patients 0.7, and F-PLX patients 0.4 doses of oxycodone in 24 hours (not significant). Average ipsilateral diaphragmatic motility was reduced to 8% in F-PLX group (p < 0.01) and to 19-30% in the other groups (p < 0.05). At 24 hours, average motility in BUPI, F-SC, F-PLX and PLX groups was 54, 48, 31 and 91%, respectively. In all groups FVC, FEV1 and PEF were reduced by 20-40% at 3 hours (p < 0.001). At 8 and 24 hours, FVC and FEV1 were in F-SC and F-PLX groups significantly lower (p < 0.05) than in PLX group. CONCLUSIONS: Use of 0.125% bupivacaine for continuous interscalene block did not prevent a deterioration of diaphragmatic motility and ventilatory function. Co-infusion of fentanyl did not significantly potentiate the block. PMID- 8489990 TI - Regional anesthesia for microvascular surgery: a combination of brachial plexus, spinal, and epidural blocks. AB - BACKGROUND AND OBJECTIVES: To evaluate the usefulness, safety, and efficacy of the combined plexus brachial, spinal, and epidural blocks in free toe to hand transplantations. METHODS: DESIGN: Prospective, case series. SETTING: Tampere University Hospital, Finland. PATIENTS: Fifteen adult patients for toe to hand microvascular transplantation under combined regional anesthesia with bupivacaine. INTERVENTIONS: The efficacy of the blocks, complications, and patient satisfaction were recorded in the study form. MEASUREMENTS AND MAIN RESULTS: The duration of operations varied between 8 and 18 hours. No major complications occurred. Vasodilatation in the operated hand was maintained during the entire operation as well as in the postoperative period, and the surgical results were satisfactory. The mean skin temperature was 5 degrees C higher in the blocked extremity compared to the opposite hand. In every patient the skin temperature of the transplant was over 32.4 degrees C after the operation. Blood pressure, heart rate, temperature and oxygen saturation were well maintained during the entire procedure. All patients were satisfied with their anesthesia. Back pain occurred in 11 patients and in two it was considered severe. One patient may have had a systemic toxic reaction (shivering) due to high plasma levels of bupivacaine, but the symptom was transient. CONCLUSION: Combined regional anesthesia is an alternative to general anesthesia in prolonged microsurgical operations and it appears to improve perfusion of the transplanted extremity. PMID- 8489991 TI - Nutrient intake by duration of ex-smoking in the Scottish Heart Health Study. AB - Information on current-, never- and ex-smokers (including duration of cessation) was obtained in a cross-sectional survey of risk factors for coronary heart disease (CHD), the Scottish Heart Health Study. Diet was also assessed by food frequency questionnaire in a total of 4265 men and 4770 women. Nutrient intakes were computed by sex and smoking group and, according to their diet, the ex smokers were categorized as current- or never-smokers using discriminant analysis techniques. The current- and five ex-smoking groups differed negligibly in past smoking characteristics. Energy-adjusted intake of polyunsaturated fat, fibre and the antioxidant vitamins were lowest in current-smokers, and for men, intakes increased progressively with duration of ex-smoking to reach the level of never smokers. In a similar manner, energy, sugar and alcohol decreased with duration of ex-smoking. Fewer trends were observable for women, and the diets of ex smokers more immediately resembled that of never-smokers. Discriminant analysis for the combined nutrients correctly categorized 72 and 69% of male, and 66 and 65% of female current- and never-smokers respectively. By 4 years of smoking cessation the general dietary pattern of ex-smokers was similar to never-smokers for both sexes. Whether this represents a change in diet over time or a cohort effect is unclear, but the results do suggest that the apparent healthier diet of ex-smokers may contribute to their reduction in CHD risk compared with life-long current-smokers. PMID- 8489992 TI - The respiratory quotient in relation to fat deposition in fattening-growing pigs. AB - The relationship between non-protein respiratory quotient (RQnp) and total fat retention (RFAT) or fat retained from synthesized carbohydrates (RFAT(CHO)) was evaluated from experiments with fattening--growing pigs in the live weight (LW) range from 45 to 120 kg. A commercial feed compound (31 g fat/kg) was fed at low (LI) or high (HI) feed intake in Expt 1, while a semi-purified diet (9.5 g fat/kg) was given without (LO) or with (HO) supplement of 90 g soya-bean oil/kg in Expt 2. RQnp was calculated from 24 h measurements of the gas exchange, RFAT from 7 d N and C balances and RFAT(CHO) from differences between RFAT and digested fat. The measurements showed that about 85% of the total gas exchange was caused by oxidation of non-protein nutrients and the RQnp varied from 1.00 to 1.34. In Expt 1 RFAT increased with LW from 46 to 141 and from 199 to 335 g/d on LI and HI respectively, whilst in Expt 2 RFAT increased from 191 to 377 and from 267 to 511 g/d on LO and HO respectively. A pronounced linearity was found between RQnp and RFAT for all diets, but the curve for Expt 2 on HO had a lower position than the common curve for the other diets. By relating RQnp to RFAT(CHO) a common linear curve and regression equation could be established in spite of the great variation in dietary composition, intake of fat and fat deposition. PMID- 8489993 TI - Hindlimb protein turnover and muscle protein synthesis in lambs: a comparison of techniques. AB - A combination of arterio-venous difference, kinetic isotope transfer and blood flow rate techniques were used to measure tyrosine metabolism across hindlimb tissues of nine growing lambs (average live weight 36.5 kg) fed on a range of dry matter intakes. Muscle protein synthesis was measured using a continuous infusion technique and compared with simultaneous estimates of hindlimb protein turnover calculated from the values for tyrosine metabolism. When the specific radioactivity (SRA) of tyrosine in the arterial plasma free pool was assumed to be the same as the SRA of tyrosine in the direct precursor pool of protein synthesis, hindlimb protein synthesis (ksav; 3.66 (SEM 0.50) %/d) was significantly (P < 0.001) higher (68%) than muscle protein synthesis (ksp; 2.18 (SEM 0.31) %/d) but was similar to the value for muscle protein synthesis calculated using the homogenate free tyrosine SRA (ksh; 3.35 (SEM 0.42) %/d). Hindlimb and muscle protein synthesis (y) were both significantly related to dry matter intake (chi) (ksav, r2 0.667, P = 0.007; ksh, r2 0.968, P < 0.001) and there was no significant difference between the slopes (P = 0.532) and intercepts (P = 0.945) of the two regression lines. The results demonstrate that hindlimb protein turnover cannot be quantitatively compared with muscle protein synthesis, probably due to high protein metabolic activity in non-muscular tissues within the hindlimb, although similar responses in protein synthetic rate to the level of feed intake were observed between hindlimb and muscle tissues. PMID- 8489994 TI - Impact of exocrine pancreatic adaptation on in vitro protein digestibility. AB - An in vitro enzymic method was used to study the kinetics of digestion of casein and rapeseed proteins. After a predigestion step with pepsin (EC 3.4.23.1), the protein substrates were submitted to a 24 h hydrolysis either with pancreatin or pancreatic juices of pigs adapted either to casein or rapeseed diets and whose enzyme activities were different. After 3, 6 and 24 h of in vitro digestion, dialysates were collected and analysed for content of nitrogen, amino acids and low-molecular-weight peptides. For a long-term hydrolysis (24 h), overall digestibility of both substrates was not affected by the composition of pancreatic enzyme mixtures. However, at the beginning of hydrolysis a significant effect of pancreatic juices was observed, i.e. individual amino acid digestibility was generally higher when casein pancreatic juice was used for hydrolysis and their relative pattern of release was modified. For both substrates the proportion of amino acids released as low-molecular-weight peptides was not affected by the enzyme mixture used and made up about two-thirds of the total digested material. It is concluded that exocrine pancreatic adaptation to protein sources does not affect the total capacity of protein digestion. However, the changes in initial kinetics of release of amino acids are more dependent on the nature of the protein tested than on the composition of pancreatic enzyme mixtures. PMID- 8489995 TI - Effect of some gastrointestinal hormones on motor and electrical activity of the digestive tract in the conscious cat. AB - Three peptides structurally related to gastrin and known to be full agonists of antral motility in the conscious cat, pentagastrin (PG), cholecystokinin (CCK) and synthetic octapeptide of cholecystokinin (OP-CCK), were compared in relation to antral and duodenal electrical activity. They induced the same antral effect in eliciting an increase in the basal electrical rhythm (BER) and a short-lasting decrease in the frequency of the bursts of spikes. The electrical changes were correlated with lumen pressure changes measured in parallel, consisting of a decrease in the frequency of high-amplitude peaks and an increase in low amplitude peaks. The additive effect of PG and CCK shows that the peptides are full agonists for antral electrical activity, as they are for antral motility and acid secretion. In contrast to the antrum, the three peptides increased the frequency of the duodenal spike bursts, CCK and OP-CCK decreased the BER frequency, while PG increased BER slightly. The increase in antral and duodenal BER obtained after a beef-liver meal, which produced a large endogenous gastrin release, suggests a major role for gastrin in antral motility induced by feeding, at least in the cat. PMID- 8489996 TI - Absorption of volatile fatty acids from the rumen of lactating dairy cows as influenced by volatile fatty acid concentration, pH and rumen liquid volume. AB - The effect of rumen liquid volume, pH and concentration of volatile fatty acids (VFA) on the rates of absorption of acetic, propionic and butyric acids from the rumen was examined in lactating dairy cows. Experimental solutions introduced into the emptied, washed rumen comprised two different volumes (10 or 30 l), four levels of pH (4.5, 5.4, 6.3, 7.2) and three levels of individual VFA concentrations (20, 50 or 100 mM-acetic, propionic or butyric acid). All solutions contained a total of 170 mM-VFA and an osmotic value of 400 mOsmol/l. Absorption rates were calculated from the disappearance of VFA from the rumen corrected for passage with liquid phase to the omasum. An increase in initial fluid pH caused a reduction in fractional absorption rates of propionic and butyric acids. Increasing the initial pH from 4.5 to 7.2 reduced fractional absorption rates of acetic, propionic and butyric acids from 0.35, 0.67 and 0.85 to 0.21, 0.35 and 0.28/h respectively. The fractional absorption rates of all VFA were reduced (P < 0.05) by an increase in initial rumen volume. The fractional absorption rate of acetic acid was lower (P < 0.05) at an initial concentration of 20 mM than of 50 mM. The fractional absorption rate of propionic acid tended (P < 0.10) to decrease as the level of concentration increased while fractional absorption rate of butyric acid was not affected by butyric acid concentration. These results indicate that relative concentrations of VFA in rumen fluid might not represent relative production rates and that attempts to estimate individual VFA production from substrate digestion must take account of pH and VFA concentration. PMID- 8489997 TI - Comparative effects of four legume species on plasma lipids and faecal steroid excretion in hypercholesterolaemic pigs. AB - The effect of four species of legume seeds on plasma cholesterol levels and faecal steroid excretion was studied in pigs. Thirty-six growing boars were randomly allocated in groups of six to six diets which they ate continuously for 42 d. The diets fed were: 1, a semi-purified (SP; control group 1) diet; 2, SP + 10 g cholesterol/kg (control group 2); 3, 4, 5, 6, SP + cooked legumes (70:30, w/w; respectively baked beans (Phaseolus vulgaris), peas (Pisum sativum), lentils (Lens culinaris Medik.), butter beans (Phaseolus lunatus)) + 10 g cholesterol/kg. Fasting blood samples were taken on days 0, 14, 28, and 42 for the determination of total plasma cholesterol, high-density-lipoprotein (HDL)-cholesterol and triacylglycerols. Between days 7 and 11 and days 28 and 32 complete 5 d faecal collections were made for the measurement of neutral, acidic and conjugated steroids. After 42 d total cholesterol and HDL-cholesterol levels were raised significantly in all groups, but to different extents. In comparison with control group 2, diet-induced hypercholesterolaemia was significantly inhibited in the groups consuming baked beans, peas and butter beans, although HDL-cholesterol levels were maintained. Faecal steroid excretion by the legume groups was not significantly different from that of control group 2. The results suggest that the mechanism for the hypocholesterolaemic effect does not involve increased hepatic bile acid synthesis and thereby increased cholesterol clearance via the intestinal route. PMID- 8489998 TI - The effect of increasing levels of dietary fish oil rich in eicosapentaenoic and docosahexaenoic acids on lymphocyte phospholipid fatty acid composition and cell mediated immunity in the mouse. AB - The influence of increasing intakes of fish oil on spleen leucocyte phospholipid fatty acid composition and cell-mediated immunity was studied in the mouse using a popliteal lymph node assay technique. The immune response was suppressed by 160 g fish oil/kg diet, but not by lower doses. The proportion of 20:5n-3 in spleen leucocyte phospholipid increased from 0.14 in the controls to 3.8, 7.2, 8.5 and 9.4% in the animals fed on 25, 50, 100 and 160 g fish oil/kg diet; the proportion of 22:6n-3 increased from 5.1 in the controls to 12.1, 12.2, 12.8 and 12.9% respectively. It is concluded that moderate intakes of fish oil are not immunosuppressive. PMID- 8489999 TI - Intestinal absorption and liver uptake of medium-chain fatty acids in non anaesthetized pigs. AB - In order to study the rate of intestinal absorption and hepatic uptake of medium chain fatty acids (MCFA), six growing pigs, mean body weight 65 kg, were fitted with a permanent fistula in the duodenum and with three catheters in the portal vein, carotid artery and hepatic vein respectively. Two electromagnetic flow probes were also set up, one around the portal vein and one around the hepatic artery. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and a nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the three vessels at regular intervals for 12 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentration of non-esterified octanoic and decanoic acids in the portal blood rose sharply after the beginning of each infusion and showed a biphasic time-course with two maximum values, one after 15 min and a later one between 75 and 90 min. Only 65% of octanoic acid infused into the duodenum and 54% of decanoic acid were recovered in the portal flow throughout each experiment. The amounts of non-esterified MCFA taken up per h by the liver were close to those absorbed from the gut via the portal vein within the same periods of time, showing that the liver is the main site of utilization of MCFA in pigs. These results have been discussed with a special emphasis laid on the possible mechanisms of the biphasic time-course of MCFA absorption and the incomplete recovery in the portal blood of the infused fatty acids. PMID- 8490000 TI - The digestion process of the sugar alcohol isomalt in the intestinal tract of the pig. 1. Studies with administration of isomalt in the feed. AB - In a study with twelve pigs of 60-70 kg live weight provided with a re-entrant cannula at the end of the ileum, and twelve intact, non-cannulated pigs, the fate of dietary doses of 100 and 200 g isomalt/kg during gastrointestinal passage was examined. From sugar analyses in ileal chyme it was calculated that 0.43 and 0.30 of the isomalt consumed was digested in the small intestine with the 100 and 200 g/kg doses of isomalt respectively. From findings on ileal energy digestibility it was calculated that, because of a secondary effect of isomalt on the digestion of the basal diet, isomalt digestibility in the small intestine was distinctly lower. In faeces no sugars were found, so faecal digestibility of isomalt was 1.00 for both doses. The bacterial fermentation in the large intestine of the isomalt not digested in the small intestine caused an increase in the faecal excretion of nitrogen and energy. This increased faecal excretion was hardly (nitrogen) or not (energy) compensated by a decreased urinary excretion. PMID- 8490001 TI - The digestion process of the sugar alcohol isomalt in the intestinal tract of the pig. 2. Studies with administration of isomalt as a sweet. AB - In a study with ten pigs of 60-70 kg live weight, provided with a re-entrant cannula at the end of the ileum, and sixteen intact, non-cannulated pigs, the digestion and absorption of a dietary dose of 100 g isomalt/kg, and isomalt given between the meals as a 'sweet' on the basis of 50 and 100 g/kg feed consumption, were examined. In all three isomalt treatments slightly less than 0.40 of the isomalt consumed was digested in the small intestine when the calculations were based on ileal sugar passage. However, when basing the calculations on energy contents of ileal chyme, only approximately 0.10 was digested in the small intestine. The bacterial fermentation of the isomalt flowing into the large intestine was indicated by a decreased faecal energy digestibility and a slight reduction in faecal dry matter and nitrogen digestibility. The retention of the minerals sodium, potassium, magnesium, calcium and phosphorus was not influenced to any measurable extent when isomalt was fed. PMID- 8490002 TI - Gastrointestinal responses of rats fed on white and wholemeal breads: complex carbohydrate digestibility and the influence of dietary fat content. AB - To obtain quantitative information on the digestibility of the non-starch polysaccharides (NSP) fraction of white and wholemeal breads, rats were fed on diets in which freeze-dried bread (white, wholemeal or mixtures of the two) provided all the complex carbohydrates. In a second experiment the possibility that dietary fat concentration might influence NSP digestibility was tested by feeding diets containing 30 or 170 g maize oil/kg and either white or wholemeal bread. Multiple linear regression analysis provided little evidence of associative effects of dietary components on NSP digestibility and in the two experiments digestibilities of NSP for white and wholemeal breads were 0.77-0.82 and 0.47-0.52 respectively. Xylose- and arabinose-containing polymers were better digested than was cellulose for both breads. Replacing white by wholemeal bread markedly increased the molar proportion of butyrate in caecal volatile fatty acids at the expense of acetate. This was associated with greater flows of organic matter to the large bowel (LB) and a reduction in caecal transit time (Expt 2). There was little detectable effect of dietary maize oil concentration on NSP digestibility or on LB fermentation. All breads contained some starch resistant to pancreatic alpha-amylase (EC 3.2.1.1) without previous treatment with dimethyl sulphoxide. The digestibility of this starch fraction was not significantly different from 1.0 for all diets except that containing wholemeal bread and the higher maize oil concentration where the apparent digestibility was 0.89. PMID- 8490003 TI - Complex carbohydrate digestion and large bowel fermentation in rats given wholemeal bread and cooked haricot beans (Phaseolus vulgaris) fed in mixed diets. AB - The digestion of non-starch polysaccharides (NSP) and of resistant starch (RS) by rats fed on wholemeal-bread-based diets containing 0-450 g cooked, freeze-dried haricot beans (Phaseolus vulgaris)/kg diet was measured over the final 14 d of a 21 d feeding experiment. The bread and beans provided all the dietary polysaccharide. RS could not be detected consistently in faeces and it was assumed that this fraction was entirely fermented in the large bowel (LB). NSP digestibilities were 0.56 and 0.86 for wholemeal bread and beans respectively with no evidence that the dietary presence of beans affected digestibility of bread NSP. Bean non-cellulosic polysaccharides were highly digestible with values of 0.98, 0.88 and 0.99 for arabinose, xylose and uronic acids components respectively. There were large increases in organic matter flow to the LB when beans were fed which was associated with marked caecal hypertrophy and alterations in caecal volatile fatty acids (VFA) pattern. Calculated VFA absorption from the LB was 5-fold higher with the highest level of beans and this was reflected in higher concentrations of VFA in portal and heart blood. PMID- 8490004 TI - Assessment of fermentation in growing pigs given unmolassed sugar-beet pulp: a stoichiometric approach. AB - In four experiments growing pigs were given a cereal-based diet alone or supplemented with unmolassed sugar-beet pulp (SBP), used as a model substrate for fermentation. The rates of production of methane and gaseous hydrogen were measured and, together with the molar proportions of volatile fatty acids (VFA) in the digesta, used in stoichiometric calculations of fermentation. The resulting estimates were only one-sixth of the observed extent of digestion of SBP. Bacteriostatic levels of antibiotics reduced fermentation by more than half, as judged from the digestion of non-starch polysaccharides: allowing for the incomplete suppression of fermentation it was estimated that the production of methane and VFA could account completely for the digested SBP. The potential contribution of various routes of hydrogen disposal to the error of the stoichiometric calculations is discussed. PMID- 8490005 TI - The effect of dietary calcium intake in weanling rats on the efficiency of calcium absorption. AB - Rats were weaned onto high (HCa, 14.6 g/kg)- or low (LCa, 3.88 g/kg)-Ca diets for 12 d and the efficiency of absorption of Ca measured from 20 mg Ca (as CaCl2, labelled with 47Ca) by means of whole-body counting. The LCa group absorbed 74% of the test dose and the HCa group 60% of the test dose (P < 0.001). All animals were then given the LCa diet for 6 weeks and the absorption test repeated. This time there was no difference in efficiency of absorption (HCa 54%, LCa 57%). The femur dry weight was significantly lower in the group initially fed on the LCa diet, but the Ca concentration was similar to that of the HCa group. The results do not lend support to the suggestion that early dietary exposure to Ca manifests itself as a difference in Ca metabolism in later life. They do, however, highlight the importance of adequate Ca intake during critical periods of growth. PMID- 8490006 TI - Inhibition of haem-iron absorption in man by calcium. AB - The inhibiting effect of Ca on non-haem-Fe absorption is well established. Present studies showed that Ca inhibited haem-Fe absorption to the same extent when the same amount of Ca (165 mg Ca as CaCl2) was added to a meal. Attempts were made to examine the mechanism for this inhibition in the present studies. Meat is the only known dietary factor influencing haem-Fe absorption. The present studies were designed to examine whether Ca interfered with the enhancing effect of meat on haem-Fe absorption. We found that the inhibition was the same whether biosynthetically radio-Fe-labelled haemoglobin was given in meals with or without meat. The haem-Fe absorption ratio with:without added Ca was 0.59 (SE 0.07) when Ca was added to a hamburger meal, and 0.52 (SE 0.03) when added to a wheat roll. These values were not significantly different (t 0.95; P = 0.35). The inhibition of haem-Fe absorption by Ca is, thus, a direct effect on the absorption of haem Fe and not an indirect counteracting effect of the well-known enhancing effect of meat on haem-Fe absorption. Control studies were conducted to ensure that haem-Fe had not been degraded to non-haem-Fe during preparation of the foods. Since Ca inhibits the absorption of haem- and non-haem-Fe to the same extent, the present results strongly suggest that Ca interferes with the transport of Fe through the mucosal cell, and at a late stage, is common for haem- and non-haem-Fe transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490007 TI - The effect of exercise on the riboflavin status of adult men. AB - Six sedentary to moderately active men with biochemical signs of riboflavin deficiency were studied under metabolic ward conditions to examine the effects of physical activity on riboflavin status. All participants were subjected to additional exercise (EXER) for an 18 d period between two maintenance (M1 and M2) periods (16 and 13 d respectively) of habitual physical activity. Energy balance and riboflavin intake were maintained throughout the study. Riboflavin status, as judged by a significant reduction in erythrocyte glutathione reductase (EC 1.6.4.2) activation coefficient (EGR-AC), improved on changing from home (1.53 (SD 0.14)) to period M1 (1.36 (SD 0.21)) diets. The exercise period, however, resulted in a significant deterioration in riboflavin status (1.57 (SD 0.31)) which persisted in the subsequent period M2 (1.54 (SD 0.15)). There was a concomitant fall in the urinary excretion of riboflavin only in the EXER period, when results were expressed as a percentage of the dietary intake of riboflavin. These results suggest an increased demand for the vitamin for selective biochemical functions during exercise. However, the energy cost of walking (treadmill 4 km/h), 50 W and 100 W work-loads (bicycle ergometer) as well as delta mechanical efficiency (DME) did not change during the three metabolic periods. The urinary excretion of riboflavin was inversely related to DME (r 0.49; P < 0.05) and directly correlated with haemoglobin levels (r 0.63; P < 0.005). The present study suggests that riboflavin status further deteriorates during a short period of increased physical activity in individuals whose riboflavin status is marginal. PMID- 8490008 TI - A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. AB - The effect of riboflavin deficiency on gastrointestinal Fe distribution and loss was studied in weanling rats. Riboflavin deficiency was associated with a significant increase in crypt depth in the upper and mid small intestine and a twofold increase in the rate of crypt cell production compared with weight matched and ad lib.-fed control rats. The rate of loss of endogenous Fe, measured as faecal 59Fe after intraperitoneally administered 59Fe, was twice that from riboflavin-deficient rats compared with weight-matched controls. We suggest that while there may be a contribution from turnover of enterocytes with an enhanced Fe content, enhanced Fe loss associated with riboflavin deficiency is due predominantly to an accelerated rate of small-intestinal epithelial turnover. PMID- 8490009 TI - Vitamin C intake and plasma ascorbic acid concentration in adolescents. AB - The relationship between vitamin C intake and status was investigated in a group of adolescents (13-14 years old). Dietary intakes were assessed using a 7 d weighted dietary record method, coupled with the collection of duplicate diets. Vitamin C intakes calculated using food composition tables were compared with values obtained by direct analysis of duplicate diets. Vitamin C status was judged via measurement of plasma ascorbic acid (AA) concentration in blood samples taken after a 12-15 h fast. The relationship between calculated and analysed vitamin C intake and plasma AA concentration was examined. Average daily calculated vitamin C intakes, for the group (n 54) as a whole over a 7 d period, gave a good estimate of intake, as judged by prompt analysis of duplicate diets. However, analysed v. calculated intakes were significantly different for approximately one-third of subjects when data were examined on an individual basis. Large discrepancies between analysed and calculated values could not be accounted for on a food group basis. In all but two individuals, calculated vitamin C intake was in excess of the new reference nutrient intake (RNI, part of the new daily reference values (Department of Health and Social Security, 1991)) of 40 mg and all plasma AA concentrations were well above those used to indicate even a moderate risk of deficiency. A relationship between vitamin C intake and plasma AA was observed for both males (n 19) and females (n 35). However, the relationship was much stronger for males who showed a wider range of both intake and plasma AA values. PMID- 8490010 TI - Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women. AB - Thirty-three New Zealand women aged 18-23 years received daily for 32 weeks, 200 micrograms Se as Se-enriched yeast (selenomethionine), or brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind trial. Se supplementation raised (P = 0.001) platelet glutathione peroxidase (EC 1.11.1.9; GSHPx) activity, and also Se and GSHPx in whole blood, erythrocytes and plasma. Selenomethionine was more effective in raising blood Se concentrations than selenate, but both were equally effective in raising GSHPx activities in whole blood, erythrocytes and plasma, indicating a similar bioavailability for the two forms. These observations and those of gel filtration studies of erythrocytes and plasma proteins reported elsewhere (Butler et al. 1991) are consistent with the incorporation of Se from selenomethionine into a general tissue protein pool while selenate is directly available for GSHPx synthesis, and explain the poorer correlation between Se and GSHPx in individuals with higher Se status. However, selenate raised platelet GSHPx activities to a greater extent than did selenomethionine suggesting some other effect of selenate on platelets which needs further investigation. A response of GSHPx activity in these New Zealand subjects indicates that their dietary Se intake is insufficient to meet recommended intakes based on the criterion of saturation of GSHPx activity, and could reflect a marginal Se status. The level of blood Se necessary for saturation of GSHPx of about 100 ng Se/ml whole blood confirms observations in earlier studies. PMID- 8490011 TI - Glutathione content of the small intestine: regulation and function. AB - In ad lib.-fed rats the epithelium of the small intestine, like the liver, contains large quantities of glutathione, 17.0 and 32.4 nmol/mg protein respectively. Following 24 h food restriction the glutathione content in both tissues fell 53 and 69% respectively. Unlike the liver, however, the glutathione content of the intestinal mucosa is not regulated to a diurnal rhythm, suggesting that the liver may provide glutathione or glutathione precursors to maintain intestinal glutathione levels. Intestinal epithelial cell preparations obtained from 24 h food-deprived rats had depleted glutathione stores (50%) and as a consequence were more susceptible to the oxidizing effects of cumene hydroperoxide. These results suggest that if glutathione plays a major role in the defence of the intestinal mucosa from ingested toxins then depletion of this defence during periods of food restriction could significantly increase the susceptibility of the individual to toxins present in the diet. PMID- 8490012 TI - Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. AB - Experiments in rodent models of insulin-dependent diabetes mellitus (IDDM) suggest that destruction of pancreatic beta cells can be both initiated and inhibited by certain environmental factors such as dietary constituents. We studied nutritional impact of certain protein sources of natural-ingredient, non purified (NP) rodent diet on diabetes incidence and insulitis severity in the spontaneous diabetic, non-obese diabetic (NOD) mouse. Long-term ad lib. feeding of diets containing wheat flour (800 g/kg), and to a lesser extent soya-bean meal (400 g/kg), were associated with relatively high diabetes incidence (65 and 45% respectively), whereas a diet based on hydrolysed casein (HC; 200 g/kg) as the only source of protein significantly (compared with the wheat-flour diet) inhibited expression of diabetes (22%). Feeding a hypo-allergenic soya-bean protein hydrolysate resulted in diabetes incidence and insulitis severity similar to that of the soya-bean-meal-fed group. This may indicate that protein hydrolysis per se may not be necessary for dietary modification of diabetes in the NOD mouse. The window of vulnerability to diabetogenic diets was found to be between weaning and about 70 d of age. In the diabetic mice insulitis was less frequent in the HC-fed group when compared with those fed NP (P = 0.04), soybean meal (P = 0.03), soya-bean-protein hydrolysate (P = 0.012) or wheat flour (P = 0.0002). In the non-diabetic mice the wheat-flour diet was associated with a high insulitis severity in comparison with the HC group (P = 0.004). Early avoidance of NP diet was associated with lower degree of insulitis in both diabetic (P = 0.00003) and non-diabetic mice (P = 0.001) when compared with the mice fed on the HC diet later in life. These findings are contributing to further clarification of diabetes-promoting dietary constituents, which may have some nutritional implications for IDDM-susceptible children. PMID- 8490013 TI - Ileal digestibility and availability of lysine in protein concentrates for pigs. PMID- 8490014 TI - The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. AB - Several variants of the beta amyloid protein, differing only at their carboxy terminus (beta 1-39, beta 1-40, beta 1-42, and beta 1-43), have been identified as the major components of the cerebral amyloid deposits which are characteristic of Alzheimer's disease. Kinetic studies of aggregation by three naturally occurring beta protein variants (beta 1-39, beta 1-40, beta 1-42) and four model peptides (beta 26-39, beta 26-40, beta 26-42, beta 26-43) demonstrate that amyloid formation, like crystallization, is a nucleation-dependent phenomenon. This discovery has practical consequences for studies of the beta amyloid protein. The length of the C-terminus is a critical determinant of the rate of amyloid formation ("kinetic solubility") but has only a minor effect on the thermodynamic solubility. Amyloid formation by the kinetically soluble peptides (e.g., beta 1-39, beta 1-40, beta 26-39, beta 26-40) can be nucleated, or "seeded", by peptides which include the critical C-terminal residues (beta 1-42, beta 26-42, beta 26-43, beta 34-42). These results suggest that nucleation may be the rate-determining step of in vivo amyloidogenesis and that beta 1-42 and/or beta 1-43, rather than beta 1-40, may be the pathogenic protein(s) in AD. PMID- 8490015 TI - Sequence-specific cleavage of DNA via nucleophilic attack of hydrogen peroxide, assisted by Flp recombinase. AB - Hydrogen peroxide is capable of effecting the cleavage of a specific phosphodiester bond in DNA, when used in concert with the recombinase enzyme Flp from Saccharomyces cerevisiae. This cleavage is not caused by oxidative damage of the DNA backbone but instead is the result of nucleophilic attack by peroxide. A single phosphorus-oxygen bond is broken in the reaction. Cleavage of DNA by peroxide also occurs with an inactive mutant of Flp in which the active site nucleophile tyrosine has been replaced by phenylalanine. Besides providing information on the mechanism of strand cleavage by Flp, these results may contribute to the development of new synthetic DNA cleavage reagents that act by hydrolytic and not radical chemistry. PMID- 8490016 TI - A structural domain (the lid) found in pancreatic lipases is absent in the guinea pig (phospho)lipase. AB - Typically pancreatic lipases are characterized by the following properties: (1) they are activated by lipid/water interfaces (interfacial activation), (2) they are inhibited by bile salts but reactivated by colipase (a small activator protein), and (3) they do not hydrolyze significantly phospholipids. A cDNA clone encoding a guinea pig pancreatic (phospho)lipase (GPL) has been sequenced and expressed. The enzyme (recombinant as well as native) differs from other pancreatic lipases in that (1) it is not interfacially activated, (2) its activity is unaffected by the presence of bile salts and/or colipase using tributyrin as substrate, and (3) it exhibits equally phospholipase A1 and lipase activities. The amino acid sequence of GPL is highly homologous to that of other known pancreatic lipases, with the exception of a deletion in the so-called lid domain that regulates access to the active centers of other lipases. We propose that this deletion is directly responsible for the anomalous behavior of this enzyme. Thus GPL challenges the classical distinction between lipases, esterases, and phospholipases. PMID- 8490017 TI - Effect of site-specifically located mitomycin C-DNA monoadducts on in vitro DNA synthesis by DNA polymerases. AB - A series of site-specifically modified oligodeoxynucleotides were synthesized that contained either of the two known mitomycin C-DNA monoadducts. In vitro DNA synthesis was carried out on some of these templates using a modified bacteriophage T7 DNA polymerase (Sequenase), AMV reverse transcriptase, and two different varieties of Escherichia coli DNA polymerase I (Klenow fragment)--one that carries the normal 3'-->5' exonuclease activity and a mutant protein that lacks this enzymatic function. Regardless of the type of DNA polymerase being used, DNA synthesis was terminated nearly quantitatively at the nucleotide 3' to each of these two monoadduct sites, although primer extension to full length of the template was noted with the unmodified control template. Substitution of Mn2+ for Mg2+ at a high concentration of the deoxynucleotide triphosphates resulted in incorporation of nucleotides opposite the adduct in the incubations with Sequenase or the 3'-->5' exonuclease-free Klenow fragment; however, primer extension beyond the adduct site did not take place. These studies demonstrated that the mitomycin monoadducts are strong blocks of replication and are likely to be toxic lesions in vivo. Since previous molecular modeling studies and molecular mechanical calculations indicated that the mitomycin adduction does not induce severe distortions at the site of adduction, a lack of base-pairing ability of the modified base in the extended product is unlikely to be the reason for the inhibitory effect. Instead, energy-minimized structural models indicated that additional hydrogen-bonding interactions have been introduced by the mitomycin moiety, and perhaps this increased thermodynamic stabilization of a distorted structure of the replication fork, in turn, may block the replication bypass. Experimental evidence of increased thermodynamic stability was provided by thermal melting of a template/primer complex that presumably a polymerase encounters in a typical replication fork. Consistently higher Tm of the adducted "replication fork" was noted when compared to its unmodified counterpart. PMID- 8490018 TI - Posttranscriptional regulation of chimeric human transferrin genes by iron. AB - Transferrin, the transferrin receptor, and ferritin are integral to the body's management of iron, an element required for life but highly toxic when present in excess. The transferrin receptor and ferritin are regulated posttranscriptionally by iron: the transferrin receptor by mRNA stability and ferritin by mRNA translation. Results described here indicate that transferrin, like ferritin, is regulated by iron at the level of translation. Chimeric genes introduced into the mouse genome were composed of the human transferrin 5' regulatory region fused to the chloramphenicol acetyl transferase (CAT) reporter gene. Iron administration to transgenic mice resulted in a significant decrease of transferrin-directed CAT enzyme activity and CAT protein in liver, but no significant decrease in human transferrin-CAT mRNA levels. Binding of specific RNA iron regulatory elements by proteins in cytoplasmic extracts have been shown to regulate ferritin and transferrin receptor synthesis. Similar results have been obtained with transferrin mRNA. A decreased binding of human transferrin 5'-untranslated region RNA by factors in cytoplasmic extracts of livers from mice receiving iron was found when compared to extracts from control mice. A human transferrin RNA protein complex migrated electrophoretically with the same mobility as a ferritin iron responsive element RNA-iron responsive element binding protein complex. The ferritin iron responsive element RNA also competed with the human transferrin 5' untranslated region RNA-protein complexes formed and vice versa. Therefore, iron modulation of human transferrin may share a factor common or similar to that observed in ferritin and transferrin receptor iron modulation. PMID- 8490019 TI - Specificity in the interactions of extracellular matrix proteins with subpopulations of the glycosaminoglycan heparin. AB - Many extracellular matrix glycoproteins--including laminin, fibronectin, thrombospondin, type I collagen, and other collagens--bind the glycosaminoglycan heparin, yet little is known about the functional significance of these interactions. It is also not known if heparin-binding extracellular matrix proteins recognize distinct structural elements in heparin, nor whether all extracellular matrix proteins recognize the same or different aspects of heparin structure. If extracellular matrix proteins each recognize distinct features of heparin, such specificity could be of importance in vivo, where structurally distinct heparan sulfate species occur. To investigate specificity in the binding between extracellular matrix proteins and heparin, the method of affinity coelectrophoresis (ACE) was used [Lee, M. K., & Lander, A. D. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 2768-2772]. Low M(r) (approximately 6 kDa) 125I-heparin was fractionated by electrophoresis through agarose gel lanes containing extracellular matrix proteins at various concentrations; from heparin migration patterns, binding affinities were calculated. The results indicate that fibronectin, type I collagen, and laminin--but not thrombospondin--each fractionate heparin into subpopulations that differ substantially in binding affinity. From ACE gels containing either fibronectin, type I collagen, or laminin, fractions of heparin were isolated that represent the 25% of molecules most strongly bound and the 25% least strongly bound by each of these proteins. Subsequent ACE analysis of these six fractions showed that (1) for each of fibronectin, type I collagen, and laminin, strongly- and weakly-binding heparin subfractions differ approximately 5-30-fold in Kd; (2) heparin that binds strongly to any one of fibronectin, type I collagen, or laminin also binds strongly to the other two; (3) heparin that binds weakly to any one of fibronectin, type I collagen, or laminin, also binds weakly to the other two; (4) heparin subfractions that differ greatly in affinity for fibronectin, type I collagen, and laminin show little difference in Kd for thrombospondin or for the heparin-binding growth factor basic fibroblast growth factor (bFGF); (5) neither heterogeneity in molecular charge [as measured by diethylaminoethyl (DEAE) chromatography] nor size nor the presence or absence of antithrombin III recognition sequences can account for the selective binding of heparin subpopulations to fibronectin, type I collagen, and laminin. These results suggest that structural elements within heparin can confer preferential binding to extracellular matrix proteins. Sensitivity of some, but not all, extracellular matrix proteins to these structural features suggests that similar features, if present in heparan sulfates or other glycosaminoglycans, may be physiologically relevant in vivo. PMID- 8490020 TI - Specific binding of human dihydrofolate reductase protein to dihydrofolate reductase messenger RNA in vitro. AB - Dihydrofolate reductase (DHFR) is a critical enzyme in de novo purine and thymidylate biosynthesis. An RNA gel mobility shift assay was used to demonstrate a specific interaction between human recombinant DHFR protein and its corresponding DHFR mRNA. Incubation of DHFR protein with either its substrates, dihydrofolate or NADPH, or with an inhibitor, methotrexate, repressed its ability to interact with DHFR mRNA. An in vitro rabbit reticulocyte lysate translation system was used to show that the addition of exogenous human recombinant DHFR protein to in vitro translation reactions specifically inhibited DHFR mRNA translation. These studies suggest that the direct interaction between DHFR protein and its mRNA may be a mechanism for regulation of DHFR synthesis. PMID- 8490021 TI - Mutagenesis of ribosomal protein S8 from Escherichia coli: expression, stability, and RNA-binding properties of S8 mutants. AB - Protein S8, a 129 amino acid component of the Escherichia coli ribosome, plays an essential role in the assembly of the 30S ribosomal subunit and in the translational regulation of the spc operon by virtue of its capacity to bind specifically to rRNA and mRNA. To study structure-function relationships within the protein, we have constructed a vector for its high-level expression in vivo and developed efficient methods for its purification. Under our conditions, S8 accumulates to a level of 35% of the cellular protein and can be prepared at a purity of over 98% using either HPLC or a combination of ion-exchange and gel filtration chromatography. The unique cysteine residue at position 126 was replaced by alanine or serine by oligonucleotide-directed mutagenesis, and the two mutant proteins, CA126 and CS126, were expressed and isolated. The effects of the mutations on the RNA-binding ability, secondary structure, and stability of S8 were assessed. CD spectra indicated that wild-type S8 and the two mutant proteins have very similar secondary structures at 25 degrees C. In addition, both mutants are metabolically stable in vivo as inferred from pulse-chase labeling and immunoprecipitation experiments. However, while CA126 exhibits the same affinity for RNA and the same susceptibility to urea and thermal denaturation as wild-type S8, CS126 is severely impaired in its ability to interact with RNA and displays a dramatic reduction in conformational stability. Our results suggest that Cys126 is unlikely to play a specific role in RNA recognition but that it is an integral part of the RNA-binding domain of protein S8. PMID- 8490022 TI - Influence of QA site redox cofactor structure on equilibrium binding, in situ electrochemistry, and electron-transfer performance in the photosynthetic reaction center protein. AB - The native ubiquinone-10 redox cofactor has been removed from the QA site of the isolated reaction center protein from Rhodobacter sphaeroides and reconstitution attempted with 28 non-quinone molecules in order to identify factors governing cofactor function and the selectivity displayed by the site in the electron transfers that it catalyzes. Equilibrium binding, in situ electrochemistry, and the kinetics of electron transfer to and from the QA site occupant were examined. Four classes of non-quinone molecules are distinguished according to their ability to occupy the QA site and conduct intraprotein electron transfers. The minimal requirements for occupancy of the QA site are at least one ring and a heteroatom hydrogen bond acceptor. Thus, binding at the site is not highly selective. The rates of electron transfers to and from the class of non-quinone molecules (four) that satisfy the criteria for cofactor function at the QA site compare well with rates previously determined from 14 to 295 K for 14 quinone replacements with comparable values of the reaction free energy. This indicates that the rates are relatively insensitive to variations in exotic and quinone cofactor reorganization energy and the vibrational frequencies coupled to the electron transfers, and that the exotic and quinone cofactors are bound in the QA site in comparable positions. It appears that any variation in rate is determined predominantly by the value of the reaction free energy. The QA site protein cofactor solvation contribution to the in situ electrochemical potential is roughly constant for 12 rigid quinone and 2 exotic cofactors (average value-61 +/ 2 kcal/mol). Favorable electrostatic contributions governing the reaction free energy are therefore also relatively insensitive to cofactor structure. However, flexible molecules appear to encounter in situ steric constraints that lower the electron affinity by destabilizing the reduced cofactor species. This is a strong determinant of whether a molecule, once in the QA site, will function. These findings compare well with those from studies of electron transfers in synthetic systems. PMID- 8490023 TI - Picosecond fluorescence decay in photolyzed lens protein alpha-crystallin. AB - Photolysis of calf lens protein alpha-crystallin in aqueous solutions has been monitored by observing changes in fluorescence decay following UV irradiation at 308 nm. The fluorescence decay was biexponential in dark controls and in photolyzed solutions. The recovered lifetime components in pH 7.4 phosphate buffer at 23 degrees C were 3.5 and 0.5 ns before irradiation and 2.7 and 0.5 ns after irradiation. As the UV dose increased, the relative weighting coefficient of the 2.7-ns decay component decreased, and that of the 0.5-ns component increased, resulting in an overall lifetime shortening. Similar results were obtained in 5 M guanidine hydrochloride solutions where lifetime components of 2.7 and 0.5 ns were observed. These observations were in contrast to the behavior of tryptophan monomer solutions which did not show any change in fluorescence decay kinetics upon UV photolysis but only a reduced fluorescence intensity. Steady-state fluorescence spectra and fluorescence quantum yields were also measured at 23 degrees C for unirradiated bovine alpha-crystallin and gave phi F = 0.11 +/- 0.01 in pH 7.4 buffer and phi F = 0.10 +/- 0.01 in 5 M guanidine hydrochloride solutions. The combined steady-state and fluorescence decay data were consistent with assignment of the long-lived fluorescence decay component in alpha-crystallin to emission from Trp-9, which is known to photolyze relatively rapidly. The short decay component was assigned to Trp-60, which photolyzed much more slowly. We thus provide an example of using steady-state photochemical data to assign fluorescence decay components in a multi-tryptophan protein. PMID- 8490024 TI - Regioselectivity of cytochrome P-450 catalyzed hydroxylation of fluorobenzenes predicted by calculated frontier orbital substrate characteristics. AB - In the present study, a hypothesis is presented for the prediction of the regioselectivity of cytochrome P-450 catalyzed hydroxylation of fluorobenzenes. The regioselectivity of the in vivo hydroxylation of fluorobenzene, 1,2 difluorobenzene, 1,3-difluorobenzene, 1,2,3-triluorobenzene, and 1,2,4 triflurobenzene could be predicted within 6% accuracy on the basis of the substrate's frontier orbital characteristics for electrophilic attack. The in vivo regioselectivity of the hydroxylation of fluorobenzene was not significantly influenced by changes in the cytochrome P-450 enzyme pattern. This implies that the regioselectivity is not predominantly determined by the juxtaposition of the relatively small substrates in the active sites of the cytochrome P-450s catalyzing the reaction. Additional in vitro experiments using 1,2 difluorobenzene as the model substrate demonstrated that minor factors influencing the regioselectivity and possibly responsible for the 6% deviation from the calculated values in in vivo experiments might be (i) the influence of biotransformation routes occurring in vivo but not of importance in in vitro microsomal incubations and (ii) a small variation due to influences of the contribution of various cytochrome P-450 enzymes. On the basis of the results obtained, it is concluded that the aromatic hydroxylation of fluorobenzenes proceeds through an initial electrophilic attack of (FeO)3+ on the aromatic substrate, and not through initial electron abstraction followed by attack of the (FeO)2+ species on the substrate radical cation. The fact that the regioselectivity observed could be predicted and/or explained by the site of initial (FeO)3+ attack also argues against epoxides as important intermediates in the formation of phenol metabolites from fluorobenzenes. PMID- 8490025 TI - Resonance Raman studies of iron-only hydrogenases. AB - The nature of the iron-sulfur clusters in oxidized and reduced forms of Fe-only hydrogenases from Desulfovibrio vulgaris, Thermotoga maritima, and Clostridium pasteurianum has been investigated by resonance Raman spectroscopy. The results indicate the presence of ferredoxin-like [4Fe-4S]2+,+ and [2Fe-2S]2+,+ clusters in both T. maritima hydrogenase and C. pasteurianum hydrogenase I, but only [4Fe 4S]2+,+ clusters in D. vulgaris hydrogenase. This necessitates a reevaluation of the iron-sulfur cluster composition of C. pasteurianum hydrogenase I and indicates that the resonance Raman bands in the oxidized hydrogenase that were previously attributed to the hydrogen activating center [Macor, K. A., Czernuszewicz, R. S., Adams, M. W. W., & Spiro, T. G. (1987) J. Biol. Chem. 262, 9945-9947] arise from an indigenous [2Fe-2S]2+ cluster. No resonance Raman bands that could be uniquely attributed to the oxidized or reduced hydrogen activating center were observed. This suggests that the hydrogen activating center is a novel Fe center that is unrelated to any known type of Fe-S cluster. PMID- 8490026 TI - Dynamics of the internalization of phosphodiester oligodeoxynucleotides in HL60 cells. AB - We have examined the cellular association and internalization of phosphodiester (PO) oligodeoxynucleotides (oligos) with HL60 cells. At 4 degrees C, a 15-mer PO homopolymer of thymidine (FOdT15) exhibits apparent saturation binding (Km = 22 +/- 1 nM) that is competitive with the binding of phosphorothioate (PS) oligos. The value of Kc for SdC28, a PS 28-mer homopolymer of cytidine, is 5 +/- 2 nM. SdC28 was used to strip cell surface fluorescence: Internalized fluorescence accumulated in a (concentration)(time)-dependent fashion, consistent with a pinocytotic mechanism. PS, and to a lesser extent, PO oligos inhibited the rate of internalization of fluorescent albumin, also a marker of pinocytosis. This was correlated with direct in vitro inhibition of protein kinase C (PKC) beta 1 by the PS and PO oligos. Furthermore, other PKC inhibitors (H7, staurosporine, DMSO, PKC pseudosubstrate polypeptide) also inhibited intracellular accumulation of pinocytosed materials, perhaps by stimulating the exocytosis rate. In HL60 cells, the pinocytotic internalization of charged oligos appears to be dependent on intact PKC kinase activity, which is inhibited in vitro by PS and PO oligos. PMID- 8490027 TI - Estimation of the intracellular free ADP concentration by 19F NMR studies of fluorine-labeled yeast phosphoglycerate kinase in vivo. AB - Yeast phosphoglycerate kinase was selectively fluorine-labeled in vivo by inducing enzyme synthesis in stationary phase cells in the presence of 5 fluorotryptophan. Inducible expression was obtained using a galactose-inducible expression vector containing the yeast phosphoglycerate kinase coding sequence. 19F NMR measurements on intact cells showed two resolved resonances, from the two tryptophan residues in the protein, which underwent reversible changes in chemical shift under different metabolic conditions. Measurements in vitro showed that the difference in the chemical shifts of these two resonances was dependent on the adenine nucleotide concentration, in particular the MgADP concentration. A comparison of the spectra obtained in vitro with those obtained from the intact cell indicated that in glucose-fed cells the cytosolic free MgADP concentration was less than 50 microM, which is significantly lower than the concentrations measured in whole-cell extracts. PMID- 8490028 TI - Role of beta-turn in proteolytic processing of peptide hormone precursors at dibasic sites. AB - Proteolytic activation of prohormones and proproteins occurs most frequently at the level of basic amino acids arranged in doublets. Previous predictions by Rholam et al. [Rholam, M., Nicolas, P., & Cohen, P. (1986) FEBS Lett. 207. 1-6] have indicated, on the basis of 20 prohormone sequences containing 53 dibasic potential processing sites, that dibasic sites situated in, or next to, beta turns were cleaved in vivo, whereas sites included in ordered structures like beta-sheets or alpha-helices were not. We have used peptide analogs of the proocytocin/neurophysin processing domain and a purified preparation of the putative proocytocin convertase from bovine tissues as a model to demonstrate that (1) processing at dibasic sites is associated with a prohormone sequence organized in a beta-turn structure; (2) the beta-turn is an interchangeable motif since the original sequence could be replaced by an heterologous one possessing the ability to organize as a beta-turn; and (3) this particular secondary structure participates in the catalytic reaction, most likely by favoring the interactions of the substrate with the processing endoprotease. It is concluded that, in addition to the dibasic and other amino acids around the cleavage loci, the beta-turn constitutes a key feature in the proteolytic processing reaction in participating as the favorable conformation for optimal substrate-enzyme active site recognition. PMID- 8490029 TI - Biosynthesis and processing of endogenous parathyroid hormone related peptide (PTHRP) by rat Leydig cell tumor H-500. AB - We have examined in vitro the biosynthesis and processing of endogenous PTHRP in cultured rat H-500 Leydig tumor cells. Cells were grown to confluence and pulse labeled with [3H]Ile, 50 microCi/mL, in Ile free culture medium for 2 min to 6 h. In some experiments incubations were carried out in culture medium alone in the presence of 0.3 mM cycloheximide or 20 micrograms/mL unlabeled Ile. Cell extracts and culture media were analyzed by affinity chromatography employing an antibody directed against the bioactive NH2-terminal region, PTHRP(1-34), followed by gel permeation or reversed-phase high-performance liquid chromatography. Incorporation of [3H]Ile into PTHRP in cell extracts increased over 20 min during pulse labeling and then remained constant throughout the incubation period up to 6 h. In contrast, the release of [3H]PTHRP into culture medium increased progressively over 6 h. Addition of cycloheximide or unlabeled Ile almost completely blocked incorporation of [3H]Ile into newly synthesised PTHRP. Three molecular forms of PTHRP were seen which comigrated with PTHRP(1-36), PTHRP(1 86), and PTHRP(1-141) standards in both chromatographic systems employed. After 20 min these species comprised approximately 63%, 30%, and 7% of newly synthesized PTHRP, respectively. These three molecular forms of PTHRP were observed both intra- and extracellularly, and no further metabolism of these species was seen after release into conditioned medium. Pulse-chase studies demonstrated a rapid decrease of newly synthesized PTHRP forms within cells after 20 min; there was, however, a progressive increase in [3H]PTHRP in conditioned culture medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490030 TI - Site-directed alteration of three active-site residues of a pyruvoyl-dependent histidine decarboxylase. AB - The active site of histidine decarboxylase (HDC) from Lactobacillus 30a contains a pyruvoyl cofactor sitting at the interface of two molecules in a trimer. Although exhibiting hyperbolic kinetics at pH 4.8, near its optimum, HDC is cooperative at pH 7.6, indicating that the units of the trimer communicate. A Hill plot analysis shows that HDC, at pH 7.6, can be described by a two-state model. The tense (T) state has an apparent Km for histidine of 50 mM, while the relaxed (R) state has a Km of 5 mM. To explore the catalytic mechanism, three of the cross-boundary active-site residues were altered by site-directed mutagenesis and their effects observed. Ile-59 is known to act as lid on the substrate binding pocket; it was converted to Ala (I59A) and to Val (I59V). The former was inactive, attesting to the importance of this residue in the mechanism. The I59V mutant showed a decrease in Km and in kcat at pHs 4.8 and 7.6. Ile-59 appears to help orient substrate properly for catalysis; decreasing its size expands the binding site. This may allow the substrate to bind more readily, but in a number of conformations which are not optimal for catalysis. Conversion of Tyr-62 to Phe (Y62F) had no effect on catalysis but raised the Km 7-fold at pH 4.8. Asp-63 appears to form an ion pair to the substrate imidazolium. Conversion to the neutral amide (D63N) had no effect on the kcat, but raised the Km 240-fold at pH 4.8. This is consistent with the notion that the ion pair is up to 3 kcal/mol stronger than a simple hydrogen bond with the substrate. The mutant had no detectable activity at pH 7.6. PMID- 8490031 TI - G protein binding and G protein activation by nucleotide transfer involve distinct domains on tubulin: regulation of signal transduction by cytoskeletal elements. AB - Cytoskeletal proteins have been demonstrated to interact with elements which mediate neuronal signal transduction. This laboratory has shown that tubulin forms complexes with certain G proteins and transfers GTP to them, and such nucleotide transfer correlates well with the inhibition of adenylyl cyclase. A previous study showed that tubulin-G protein complex formation occurred at regions of tubulin which were likely to be involved in binding to other tubulin dimers during the process of microtubule polymerization [Wang, N., & Rasenick, M. M. (1991) Biochemistry 30, 10957-10965]. This study represents an attempt to investigate the regions of tubulin which orchestrate the transfer of GTP from tubulin to G protein. It is demonstrated that two monoclonal antibodies, with determinants in similar regions of alpha (DM1a) or beta (DM1b) tubulin, blocked (by 70-80%) the ability of tubulin dimers (with GppNHp bound) to promote a stable inhibition of adenylyl cyclase. Under the same conditions, a polyclonal antitubulin antibody caused only a slight reduction in adenylyl cyclase inhibition. None of the antibodies altered the inhibition of adenylyl cyclase induced by GppNHp in the absence of tubulin. Under conditions where tubulin GppNHp inhibited synaptic membrane adenylyl cyclase, tubulin dimers with the photoaffinity GTP analog azidoanilido-GTP (32P-AAGTP) bound transferred that nucleotide to G alpha i1 on the membrane. DM1a and DM1b blocked this nucleotide transfer. Similarly, tubulin-AAGTP transferred AAGTP to purified G proteins in solution and DM1a and DM1b blocked this process as well. Despite their ability to block the activation of Gi1 by tubulin, neither antibody altered the ability of tubulin to bind to native Gi alpha affixed to nitrocellulose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490032 TI - Conformational changes in oxidized phospholipids and their preferential hydrolysis by phospholipase A2: a monolayer study. AB - Cleavage of oxidized fatty acids by phospholipase A2 has been implicated as the first step in the repair mechanism for oxidative damage to membrane phospholipids. However, the mechanism by which this enzyme preferentially hydrolyzes oxidized fatty acyl chains is poorly understood. Using a lipid monolayer technique, we found that the molecular surface areas of 1-palmitoyl-2 (9/13-hydroperoxylinoleoyl)-phosphatidylcholine (PLPC-OOH) and 1-palmitoyl-2 (9/13-hydroxylinoleoyl)phosphatidylcholine (PLPC-OH) were increased by as much as 50% relative to the parent nonoxidized 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC). These experimental data directly indicate a drastically changed molecular conformation of oxidized phospholipids in which the hydroperoxy or hydroxy group in the sn-2 fatty acid is close to the lipid-water interface. Phospholipases A2 from porcine pancreas and from bee venom were shown to break down PLPC-OOH and PLPC-OH monolayers much faster than PLPC monolayers. In all cases, the presence of serum albumin in the subphase enhanced monolayer breakdown by extracting hydrolysis products from the monolayer, but monolayer breakdown was always much faster for oxidized than for nonoxidized PLPC. This did not appear to be due to change in the extent of monolayer penetration by phospholipase A2, since enzyme monolayer interaction studies revealed essentially identical penetration behavior of bee venom phospholipase A2 with PLPC, PLPC-OOH, and PLPC-OH monolayers. We propose that the altered molecular conformation of oxidized phospholipids facilitates access to the sn-2 ester bond, thereby ensuring their preferential hydrolysis in the presence of a phospholipase A2. PMID- 8490033 TI - Phosphorylation sites in bovine rhodopsin. AB - Bovine rhodopsin has been phosphorylated in rod outer segments by ATP and endogenous rhodopsin kinase. Mono-, di-, and triphosphorylated rhodopsins have been prepared by chromatofocusing. Nearly all of the phosphate is found in peptide 330-348, formed by digestion of phosphorhodopsins with endoproteinase Asp N. Sequence analysis of the phosphopeptides shows that monophosphorylated rhodopsin consists of a mixture containing rhodopsins phosphorylated at 338Ser and 343Ser. Diphosphorylated rhodopsin is phosphorylated at both 338Ser and 343Ser. When rhodopsin becomes triphosphorylated it does not become phosphorylated on 334Ser but appears to become phosphorylated on one or more of the four threonine residues: 335Thr, 336Thr, 340Thr, and 342Thr. PMID- 8490034 TI - Novice and expert head nurses: a comparative study of work activities and behaviours. AB - The head nurse represents a key management position in hospital organizations. This descriptive study examines the role of the head nurse and identifies differences that exist between newly appointed head nurses and experts in the position. Questionnaire, interview and nonparticipant observation methods were used to collect and analyze data. Recommendations for educational preparation, selection criteria and recruitment and retention strategies are made based upon the study results. PMID- 8490035 TI - Planning: a cyclical and participative approach. AB - In today's turbulent environment, nurse administrators are challenged to plan and deliver change on several fronts at once. Most of us lack the resources to employ full time planners, or special project personnel. At KitchenerWaterloo Hospital the Nursing Division has developed and used a cost-effective approach to planning which allows for active involvement of all key stakeholders and assures that people are working on the plans that matter most to them. In less than three years, using this approach, the Division has implemented a broad range of progressive professional initiatives despite significant energies being required for rationalization of services with a neighbouring hospital, computerization, attempted unionization, three rounds of bed closures and the stress of severe budgetary deficit. Through it all, we have been able to maintain not only our commitment to patients, families, and each other, but also an enthusiasm and optimism for nursing's present and future. PMID- 8490036 TI - Work sampling revisited: a technique for understanding nursing work. AB - This article describes the work sampling methodology as a technique to provide direct observational data for the analysis of nursing job design. Work sampling has previously been used to examine the actual work of hospital nurses under the broad categories of direct and indirect care. We assert that work sampling can also be used to examine a specific type of nursing care, and use the example of intrapartum support to illustrate this. The purpose is to discuss the potential for using work sampling as a technique to examine the actual work nurses do and provide data for analysis of nurse job design. PMID- 8490037 TI - Changing realities: an analysis of the British Health Care system and the implications for nursing. AB - The British health care system is undergoing dramatic change as it moves from a management system based on scientific management principles towards a management system based on internal market principles. This restructuring, outlined in the British Government's White Paper, "Working for Patients" (1989), will have a significant impact on the practice of nursing. The changes will seriously affect, not only the nurse at the bedside, but also nursing management roles, practices and responsibilities. Ultimately these changes will require the radical restructuring of nursing education as British nurses know it today. This restructuring is essential if nurses are to meet and surpass the difficulties they face as their present role in the health care system is challenged, and in some areas seriously undermined. Similar problems are already being faced by Canadian nurses as they struggle to redefine the goals of their profession in light of new government strategies and policies on health care. An objective analysis of the problems faced by our British counterparts may offer insight into our own difficulties, and generate some solutions. PMID- 8490038 TI - Overcoming resistance to change. AB - The pace of change in health care organizations challenges nursing administrators at all levels of management to be effective change agents. As resistance is an inevitable element in the process of planned change, inclusion of interventions to overcome resistance is critical to the change agent role. The author presents five theoretically-based strategies for reducing the levels of resistance to planned change. PMID- 8490039 TI - Childhood asthma: beyond the myths (continuing education credit). PMID- 8490040 TI - The other foot: who is an agency nurse? PMID- 8490041 TI - This is leadership. Interview by Matt Little. PMID- 8490043 TI - 'If I had a hammer': the trials & tribulations of a nurse researcher. PMID- 8490042 TI - Nursing license #000001. Profile in courage: Lena Angevine Warner--Tennessee's Nightingale. PMID- 8490044 TI - Estimation of the secondary structure and conformation of bovine lens crystallins by infrared spectroscopy: quantitative analysis and resolution by Fourier self deconvolution and curve fit. AB - The secondary structure of six bovine lens protein fractions (two alpha, three beta and one gamma-crystallin) are examined in solution and in solid forms for the first time using FTIR spectroscopy. Films of the nuclear and cortical regions of the bovine lens are also examined. The structure is quantitatively estimated from the vibrational analysis of the resolution-enhanced amide-I profile achieved by Fourier self-deconvolution and linear least-squares curve-fit algorithm. All the protein fractions fold predominantly in a beta-pleated sheet structure with little or no alpha-helical domains in solution or in lyophilized solid form. These proteins also retain their predominant beta-sheet conformation in the cellular phospholipid environment of the lens, in conformity with the structure obtained for all the mammalian species examined to date. Despite structural homology, vibrational data indicate subtle structural differences within each class of the crystallins probably due to presence of several minor substructures/subconformations. Substantial high amounts of turns (approx. 40%) observed in the beta-fractions may have a fundamental implication in stabilizing the tertiary structure of the uniquely folded-proteins vital for the transparency of the lens. These proteins in solid KBr-matrix undergo a major structural change, induced primarily by ionic interactions which refold them in a helical conformation. IR spectroscopy together with band-narrowing procedures has proven to be an effective tool to obtain structural information of proteins in solution, as solid substrates or in a complex biological tissue, such as ocular lens. PMID- 8490045 TI - Quasi-irreversible inactivation of the sarcoplasmic reticulum Ca(2+)-ATPase by simultaneous tight binding of magnesium and fluoride to the catalytic site. AB - The sarcoplasmic reticulum Ca(2+)-ATPase was inactivated quasi-irreversibly by the treatment with KF in the presence of Mg2+ and absence of Ca2+. This inactivation was Mg(2+)-dependent, and prevented by high-affinity Ca2+ binding. The enzyme was completely protected by ATP against the inactivation with an affinity consistent with that of the catalytic site for ATP. The affinity for Mg2+ in this inactivation was in agreement with that for Mg2+ in phosphorylation of the enzyme with Pi. Mg.ATP did not bind to the inactivated enzyme, whereas metal-free ATP did bind to it with a high affinity. These findings suggest that the Mg2+ binding sub-site in the catalytic site of the inactivated enzyme is occupied by tightly-bound Mg2+. The enzyme was completely protected by Pi against the inactivation with an affinity consistent with that of the catalytic site for Pi. The inactivated enzyme showed neither phosphorylation with Pi nor high affinity vanadate binding. These findings suggest that the phosphorylation site of the inactivated enzyme is occupied by tightly-bound F-. The contents of tightly-bound Mg2+ and F- in the inactivated enzyme were determined after unbound Mg2+ and F- were removed by gel filtration. 2.3 mol of Mg2+ and 3.7 mol of F- per mol of phosphorylation sites were tightly bound to the enzyme. The tight binding of these ligands depended on the presence of each other, and was completely prevented by high-affinity Ca2+ binding. Linear relationships were found between the contents of the tightly-bound ligands and the extent of the enzyme inactivation. The tightly-bound Mg2+ and F- were entirely released by low affinity Ca2+ binding, and correspondingly the ATPase activity was restored. It is concluded that the observed enzyme inactivation is caused by simultaneous tight binding of Mg2+ and F- to the catalytic site. PMID- 8490046 TI - Activation of enzymes in organic media at low water activity by polyols and saccharides. AB - Horse liver alcohol dehydrogenase and alpha-chymotrypsin were deposited on a porous support material, Celite. After equilibration at a well-defined water activity, the catalytic activity was measured with diisopropyl ether as reaction medium. The effects of the presence of polyols and simple saccharides in the preparations were investigated. The additives caused a considerable increase in the amount of water bound to the preparation at a fixed water activity. At low water activities the catalytic activity was increased and at high water activity it was decreased by the additives. The presence of additives increased the ratio of alcoholysis-to-hydrolysis activity of chymotrypsin. PMID- 8490047 TI - Purification, characterization and molecular cloning of an acidic amino acid specific proteinase from Streptomyces fradiae ATCC 14544. AB - We have isolated a novel acidic amino-acid-specific proteinase from Streptomyces fradiae ATCC 14544, using benzyloxycarbonyl-L-Phe-L-Leu-L-Glu-p-nitroanilide (Z Phe-Leu-Glu-pNA) as a substrate. A proteinase, which we propose to call SFase, was purified from the culture filtrate by salting out, repeated S-Sepharose chromatography, and affinity chromatography (CH-Sepharose-Phe-Leu-D-Glu-OMe). The purified enzyme showed a single band having an apparent molecular weight of 19,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. When synthetic peptides were used as substrates, SFase showed high specificity for Z Phe-Leu-Glu-pNA. Comparison with nitroanilides of glutamic acid and aspartic acid as substrates revealed that the reactivity was about 10-fold higher for a glutamyl bond than an aspartyl bond. SFase selectively hydrolyzed the -Glu-Ala bond of two glutamyl bonds in the oxidized insulin B-chain within the initial reaction time until the starting material was completely digested. Diisopropylfluorophosphate and benzyloxycarbonyl-Phe-Leu-Glu chloromethylketone completely inhibited SFase, while metalloproteinase inhibitors, such as EDTA and o-phenanthrolin, did not inhibit the enzyme. The findings indicate that SFase can be classified as a serine proteinase, and is highly specific for a glutamyl bond in comparison with an aspartyl bond. To elucidate the complete primary structure and precursor of SFase, its gene was cloned from genomic DNA of the producing strain, and the nucleotide sequence was determined. Consideration of the N- and C terminal amino-acid sequences of the mature protein of SFase indicates that it consists of 187 amino acids, which follows a prepropeptide of 170 residues. In comparison with the acidic amino-acid-specific proteinase from Streptomyces griseus (Svendsen, I., Jensen, M.R. and Breddam, K. (1991) FEBS Lett. 292, 165 167), SFase had 82% homology in the amino acid sequence. The processing site for maturation of SFase was a unique sequence (-Glu-Val-), so that the propeptide could be released by cleavage of the peptide bond between Glu and Val. PMID- 8490048 TI - Characterization of the covalent chromatography of thymidylate synthase on thiopropyl-Sepharose 6B. AB - We have examined the covalent chromatography of Lactobacillus casei thymidylate synthase on thiopropyl-Sepharose 6B resin. This enzyme is a dimer of identical subunits, each of which contains one active site that features a catalytic sulfhydryl group (Cys-198). Reversible coupling was achieved via the attack of one of the enzyme's two catalytic cysteine residues, causing displacement of 2 thiopyridone, the reactive moiety of the resin. To establish the usefulness of this matrix for immobilization and the conditions required for chromatography, model studies were conducted with 2,2'-dithiodipyridine. The chemical modification of thymidylate synthase with 2,2'-dithiodipyridine was shown to be specific for the catalytic sulfhydryl groups of the native dimer, titrating 1.51 sulfhydryl groups, while 2.93 cysteines were modified in the GnHCl-denatured protein. The former reaction, which resulted in total loss of enzyme activity, was reversible with complete recovery of control activity within 30 min after addition of 100 mM 2-mercaptoethanol. Characterization of the protein pools generated in the covalent chromatography procedure indicated that the enzyme fraction washing through the column without attachment had substantially lower catalytic and ligand binding activities than the original protein stock; conversely, the enzyme fraction eluted from the column by 2-mercaptoethanol exhibited higher levels of these activities. Gel electrophoresis studies further illustrated that the unique application of the covalent chromatography technique described herein fractionated homogeneous thymidylate synthase protein into enzyme pools exhibiting distinct biochemical properties. As immobilization reaction times were increased beyond 6 h, the coupling of thymidylate synthase was demonstrated to occur through more than one enzymic sulfhydryl group. Interestingly, no covalent coupling was detected in attempts using activated thiol-Sepharose 4B, a result underlining the importance of the structure of the resin linker arm in enzyme immobilization. PMID- 8490049 TI - A comparison of the effects of dietary selenium on selenoprotein expression in rat brain and liver. AB - In studies with rodents, when dietary supplies of the essential nutrient Se are restricted, in most tissues there are parallel substantial losses of the element and the important antioxidant selenoenzyme glutathione peroxidase (GPx) for which it is a cofactor. In brain, however, there appears to be both a sequestration of Se and a conservation of GPx activity when dietary Se is limited. To further explore the relation between these phenomena, we have undertaken a comparison of the effects of diets low, normal and high in Se on GPx activity, and labeling of selenoproteins following short-term (72 h) in vivo exposure to 75Se, in subcellular fractions from rat brain and liver, the latter serving as a representative tissue which does not retain Se and is depleted of most GPx activity following dietary restriction. Brains and livers from animals on the three diets showed different patterns of response with respect to both GPx activity and retention of the 75Se dose. The low-Se diet (0.006 ppm) substantially reduced GPx activity in liver but not brain, while high levels (1 ppm) did not increase GPx in either tissue relative to a normal (0.1 ppm) intake. The 75Se was retained in brain homogenates and subcellular fractions to the greatest extent by rats on the restricted diet, while in liver, retention was greater in rats fed the normal supplement than in animals on either the low- or high-Se diets. Levels of non-protein-bound 75Se were higher in brain than liver and increased with dietary Se in both tissues. When proteins in brain and liver homogenates and subcellular fractions where separated by one-dimensional SDS-PAGE and exposed to X-ray film, the resulting autoradiograms revealed the existence of seven distinct selenoprotein bands in brain and eight in liver. Different patterns of selenoprotein expression were observed in subcellular fractions isolated from both tissues. Dependence of levels of individual selenoproteins on diet paralleled the effects on 75Se retention. Dietary influences on expression of protein bands tentatively identified as GPx were more pronounced in liver than brain. All of these observations provide further evidence of the unique nature of Se metabolism in brain. PMID- 8490050 TI - Catalytic properties of cytochrome P-450scc purified from the human placenta: comparison to bovine cytochrome P-450scc. AB - Cytochrome P-450scc was purified from the human placenta by extraction of mitochondria with cholate and Emulgen 911, chromatography on phenyl-Sepharose and DEAE-Sephacel, and ammonium sulphate fractionation. The catalytic properties of the purified human cytochrome P-450scc were analysed in Tween-20 micelles and compared to those of bovine adrenal cytochrome P-450scc analysed in the same system. Both enzymes had the same Km for cholesterol and were stimulated by cardiolipin when the cholesterol concentration was subsaturating. Examination of the rates of pregnenolone synthesis from 20 alpha-hydroxycholesterol, 22R hydroxycholesterol and 20 alpha, 22R-dihydroxycholesterol by human and bovine cytochromes P-450scc revealed that the first hydroxylation (22R position) was rate-limiting for both in Tween-20 micelles. The rate of the 22R-hydroxylation was further decreased when a 20 alpha-hydroxyl group was already present on the cholesterol side-chain. The second hydroxylation occurred at about the same rate as the third hydroxylation for both enzymes. The rate of side-chain cleavage of 25-hydroxycholesterol by human cytochrome P-450scc in Tween-20 micelles was low, the highest rate being about 1% of the Vmax for cholesterol. Substrate inhibition was seen with high concentrations of 25-hydroxycholesterol. Conversion of 25 hydroxycholesterol to pregnenolone was accompanied by a build-up of products with intact side-chains, which were probably intermediates of the reaction. Side-chain cleavage of 25-hydroxycholesterol by bovine cytochrome P-450scc showed similar characteristics to the human enzyme, except that the highest velocity observed was approx. 25% of the Vmax for cholesterol. Rates of cleavage of 25 hydroxycholesterol by both enzymes were higher in dioleoylphosphatidylcholine vesicles than in Tween-20, but were still well below the Vmax for cholesterol and showed substrate inhibition. This study shows that there is close similarity in catalytic properties between human and bovine cytochromes P-450scc which suggests that the active site of the cytochrome is highly conserved. PMID- 8490051 TI - Catalytic efficiency of expressed aromatase following site-directed mutagenesis. AB - Mutant aromatase cytochrome P-450s, expressed in CHO cells after transfection with cDNAs, have been characterized in terms of their catalytic efficiencies. After solubilization from microsomes, specific aromatase P-450 content of wild type and mutants Pro308Phe, Asp309Asn, Asp309Ala and Phe406Arg was quantitated by a sandwich enzyme-linked immunosorbent assay (ELISA). Microsomal aromatase activity was determined by the 3H-water method using [1 beta-3H]androstenedione as substrate. Estimations of the actual turnover rate (catalytic efficiency) were derived from the combined data. The P-450 content in the mutants varied but was always less than that in the wild type. Hence, the decreases in the Vmax observed in the mutant enzymes did not correlate completely with reductions in catalytic effectiveness. In recent studies on the structure-function relationship of aromatase cytochrome P-450, the observed reduction of enzyme activity in terms of Vmax following site-directed mutagenesis led to the assumption that there was a corresponding loss of catalytic effectiveness. The present study reveals that a lower P-450 content can contribute significantly to decreasing catalytic activity in the mutants. In fact, in mutant Phe406Arg which exhibited virtually no catalytically active aromatase, the specific P-450 content was below the detectable level. Because of its location, the result of this latter mutation could be a major structural perturbation of the heme-binding property. Thus, interpretation of losses and reductions in aromatase activity resulting from single amino-acid replacement should take into account changes in the specific content of aromatase cytochrome P-450. PMID- 8490052 TI - Identification and immunohistochemistry of retinol dehydrogenase from bovine retinal pigment epithelium. AB - We studied the properties of retinol dehydrogenase (11-cis-specific) from bovine retinal pigment epithelium. Detergents caused a loss of retinol dehydrogenase activity; therefore, we added 3 mM NADH as a stabilizer to solubilize this enzyme and partially purified this enzyme using Sepharose CL-6B and hydroxyapatite column chromatography. The partially-purified sample, which contained two major proteins (66 kDa, 33 kDa), had substrate preference to 11-cis and 13-cis-retinal but not to all-trans and 9-cis isomers. Monoclonal anti-33 kDa protein of retinal pigment epithelial crude extract by Western blotting. In addition, we found that monoclonal anti-retinol dehydrogenase antibody bound specifically to retinal pigment epithelium and not to Muller cells or to rod outer segments by immunohistochemical methods. PMID- 8490053 TI - A comparative study of the solution structures of tachyplesin I and a novel anti HIV synthetic peptide, T22 ([Tyr5,12, Lys7]-polyphemusin II), determined by nuclear magnetic resonance. AB - The solution structure of tachyplesin I, which was isolated from membrane acid extracts of the hemocytes from the Japanese horseshoe crab (Tachypleus tridentatus), was determined by nuclear magnetic resonance (NMR) and distance geometry calculation. Tachyplesin I takes an antiparallel beta-sheet structure with a type-II beta-turn. Recently, among more than 20 synthetic peptides associated with tachyplesin and its isopeptide (polyphemusin), we found that a novel compound, which we designated as T22 ([Tyr5,12, Lys7]-polyphemusin II), strongly inhibited the human immunodeficiency virus (HIV)-1-induced cytopathic effect and viral antigen expression. The solution structure of T22 was investigated using NMR, and its secondary structure was confirmed to be similar to that of tachyplesin I. The anti-parallel beta-sheet structure and the several amino-acid side chains on the plane of the beta-sheet of T22 are thought to be associated with the expression of anti-HIV activity. PMID- 8490054 TI - Aryl sulfotransferase-IV-catalyzed sulfation of aryl oximes: steric and substituent effects. AB - The aryl sulfotransferases (EC 2.8.2.1) catalyze the sulfation of a wide variety of hydroxyl-containing molecules. The enzyme reaction requires 3' phosphoadenosine-5'-phosphosulfate as the sulfate donor and several isozymes with broad, overlapping substrate specificities have been identified. One of the isozymes in rat hepatic cytosol, isozyme IV, is a major contributor to enzymatic sulfation. It exhibits the broadest substrate specificity of the three isozymes which have been characterized to date. Its substrates include a wide variety of phenols, certain aromatic hydroxylamines and benzylic alcohols. The latter two substrate types have implicated this isozyme in the bioactivation of several toxic compounds. Relatively little information is available, however, on substrate molecular features which account for the ability of isozyme IV to sulfate compounds not utilized by isozymes I and II. A recent investigation of isozymes I and II with a series of model aryl-oxime substrates suggested that catalysis is influenced primarily by steric factors and in particular substrate planarity and hydroxyl group orientation (Mangold et al. (1989) Biochim. Biophys. Acta 991, 453-458). In the present study, isozyme IV was investigated to characterize its substrate requirements with a more extensive series of aryl oxime substrates. The results indicated that isozyme IV has a much less stringent requirement for planarity and hydroxyl-group orientation than isozymes I or II. Isozyme IV accepted a greater variety of aryl-oxime substrates, including several classes which were not substrates for isozymes I and II. A comparison of kinetic constants and catalytic efficiencies suggested that substituent effects play a role in the sulfation of aryl oximes by isozyme IV. PMID- 8490055 TI - Stimulated cellular immune system in patients with congestive heart failure. AB - In this cross-sectional study, we analysed serum concentrations of soluble markers of cellular immune activation, namely, interferon-gamma, neopterin (a product of activated macrophages), soluble interleukin-2 receptor, and soluble CD8, in 25 patients with congestive heart failure. Ten (40%) patients showed increased concentrations (i.e. above the reference ranges of healthy controls) of neopterin, 14 (56%) showed increased soluble interleukin-2 receptor, and 6 (24%) showed increased soluble CD8. Endogenous interferon-gamma was detectable in 10 patients (40%). In addition, we found significant correlations between neopterin and interferon-gamma (rs = 0.417, p < 0.05), and between neopterin and soluble CD8 concentrations (rs = 0.430, p < 0.05). All patients with increased soluble CD8 also had increased soluble interleukin-2 receptor. However, no significant correlations of soluble interleukin-2 receptor with soluble CD8 or any of the other quantities were observed. Increased concentrations of soluble interleukin-2 receptors, soluble CD8 and neopterin indicate that cellular immunity is stimulated in patients with congestive heart failure. Activated CD8-positive T lymphocytes may represent the source of increased soluble CD8. Endogenous interferon-gamma, which is derived from activated T-cells, may induce neopterin release by monocytes/macrophages. PMID- 8490056 TI - Abnormal bilirubin binding to human serum albumin in a patient with unusual myeloma immunoglobulin G. AB - The binding of bilirubin was analysed in the serum of a patient with unusual myeloma. This patient presented an acquired Von Willebrand's disease due to the presence of a ternary complex formed by one molecule of myeloma immunoglobulin G and two molecules of albumin (Harle et al. La Presse Medicale 19, 1661-1664 (1990)). The binding characteristics of bilirubin--number of sites (n) and association constants (k)--were estimated in the serum of the proband, and compared with those of purified human serum albumin and pooled normal human serum. The data suggest that complex formation between albumin and immunoglobulin induces abnormal bilirubin binding in the patient's serum, which becomes apparent when the bilirubin/albumin ratio exceeds 1.3. This abnormal binding may be due to conformational changes of the albumin molecule in the complex. The greatly increased number of lower affinity binding sites for bilirubin is certainly due to the abnormally high concentration of myeloma immunoglobulin G in the serum of the patient. PMID- 8490057 TI - Biochemical diagnosis of a fatal case of Gunther's disease in a newborn with hydrops foetalis. AB - The birth of a male baby was induced at 32 weeks. In utero, the child presented, inter alia, signs of hydrops, hepatosplenomegaly and anaemia. Two in utero transfusions for correction of the anaemia were performed at 28 and 29 weeks, respectively. The baby rapidly presented respiratory distress with mixed acidosis. Three hours after birth, pink urine was excreted. Signs of icterus necessitated phototherapy, after which photosensitivity occurred. Erythrocytes were fluorescent under long-wavelength UV light. The baby died 24 hours after birth, displaying severe acidosis, a diffuse haemorrhagic syndrome, and repeated brady-cardia which did not respond to isoprenaline. The analysis of porphyrins in urine, blood and faeces of the baby gave the following results: 1) uroporphyrin (I and III isomeric series) was increased in urine and faeces, with traces in erythrocytes and plasma; 2) heptacarboxyporphyrin I was found mainly in urine and much less in erythrocytes, plasma and faeces; 3) coproporphyrin I was increased in urine, erythrocytes, plasma and faeces, and 4) 5-aminolaevulinic acid and porphobilinogen in urine and plasma were within the reference ranges. Determination of the enzymes of haem biosynthesis in erythrocytes and lymphocytes showed that both parents possessed only 50% of the normal activity of cosynthase. A previously described point mutation in codon 73 was observed in one parent. Fatal cases of neonatal Gunther's disease are extremely rare and such an observation, according to our knowledge, is probably one of the first described. PMID- 8490058 TI - A comparative study of urinary xanthopterin and neopterin in liver diseases. AB - By adsorption to activated charcoal, various pteridine derivatives in human urine are oxidized to xanthopterin. Following this oxidation, xanthopterin in urine from healthy subjects and from patients with liver diseases was assayed by high performance liquid chromatography. The mean values for xanthopterin in healthy subjects were 532 +/- 116 mumol/mol creatinine (mean +/- SD) in males and 585 +/- 153 mumol/mol creatinine in females; the difference was statistically significant (p < 0.01). Xanthopterin concentrations in patients with liver disease were significantly higher than those in normal subjects. When compared with urinary neopterin, which is a marker of activated cell immunity, xanthopterin was significantly increased even in fatty liver disease. These findings suggest that increased concentrations of urinary xanthopterin in liver diseases reflect not only the status of activated cell-mediated immunity, but also injury to liver cells. PMID- 8490059 TI - Lipoprotein(a) concentrations are increased in patients with myocardial infarction and angiographically normal coronary arteries. AB - It is generally accepted that Lp(a) is an independent risk factor of cardiovascular diseases. Since the apolipoprotein component of Lp(a) shows some homologies to plasminogen, it is, however, unclear as to whether the pathological effect is due to the role played by the lipoprotein in lipid metabolism or in the fibrinolytic system. We compared two groups of patients with myocardial infarction, with and without angiographically documented coronary artery disease. In the latter group, imbalances in the clotting system are very likely, while members of the former group may also display disturbances of lipid metabolism. The results show that the two groups display differences in lipid metabolism, whereas they have similar patterns of thrombogenicity indices and Lp(a) values. This study seems to support the hypothesis that Lp(a) does play a role in the fibrinolytic system, since even those myocardial infarctions without obstructive coronary artery disease have a high frequency of Lp(a) concentrations above 300 mg/l, i.e. similar to the situation found in the myocardial infarctions with angiographically documented coronary artery disease. Whether the high Lp(a) concentrations in the two groups are related to an impaired fibrinolysis will be the subject of further investigation. PMID- 8490060 TI - Serum creatinine and the DuPont dimension: possible improvements. AB - A study is reported on the determination of creatinine with the DuPont Dimension, paying special attention to interference by bilirubin. Various methods for dealing with bilirubin interference are described, including modification of the Jaffe reaction, enzymatic assay of creatinine, enzymatic destruction of bilirubin, and ultrafiltration of the serum sample. None of these modifications gave completely satisfactory results, although the Jaffe method with a ferricyanide oxidation step, and the enzymatic assay with ferrocyanide gave reasonable results with icteric specimens from adult patients, while only the latter method could be used for neonatal serum samples. PMID- 8490061 TI - Semiquantitative assay of human chorionic gonadotropin by a simple and fast immunofiltration technique. AB - An immunofiltration technique for the semiquantitative assay of human chorionic gonadotropin (hCG) was applied in two versions, using different antibodies. One anti-beta hCG subunit was immobilized on a glass microfibre disc in the form of six radially located bars, and the dry disc was placed on a water-absorbing material in a plastic device. A second antibody labelled with horse radish peroxidase conjugate was used in solution. For the colour reaction a solution with tetramethylbenzidine and hydrogen peroxide was used. The number of blue bars appearing on the test disc depended on concentration range of human chorionic gonadotropin. The technique with the monoclonal antibodies, anti-beta hCG and anti-alpha hCG-horse radish peroxidase conjugate, was specific for intact human chorionic gonadotropin, while the technique with the rabbit antibodies, raised against synthetic fragment 122-145-beta hCG and beta hCG-horse radish peroxidase, was useful for both intact human chorionic gonadotropin and its beta-chain. Cross reactions with human lutropin and thyrotropin were negligible. Haemoglobin, urea and various tested drugs did not affect the assay. In the assay of human chorionic gonadotropin in the urine of pregnant women and in sera of patients with trophoblastic diseases, the results from the immunofiltration technique were in accordance with data obtained by classical ELISA and by two commercial kits. PMID- 8490062 TI - Ektachem slides overestimate serum albumin in patients with nephrotic syndrome. AB - In a non-selected patient population (n = 140), serum albumin concentrations obtained with Ektachem slides were very significantly correlated with results determined with serum protein electrophoresis on Olympus Hite 200. In 7 patients with nephrotic syndrome, however, no such correlation existed, concentrations on Ektachem being 20 to 200% higher (up to 16 g/l difference). In other samples, albumin concentrations on Ektachem were 10 g/l lower. Between-method differences appeared most closely correlated with the sum of alpha 1- and alpha 2-globulins as determined by serum protein electrophoresis. Immunonephelometric determination of various serum proteins demonstrated that haptoglobin concentrations most closely paralleled the observed between-method differences. PMID- 8490063 TI - Evaluation of a fully mechanised immunoassay--Enzymun-Test System ES 300--and comparison with in-house methods for 8 analytes. AB - The following analytes were determined with the automated enzyme immunoassay unit, Enzymun-Test System ES 300, and by routine in-house tests, and the results were compared: thyrotropin, free thyroxine, cortisol, immunoglobulin E, digoxin, digitoxin, insulin and carcinoembryonic antigen. The methods used for comparison included two radioimmunoassays, one with enzyme labelling, two with fluorescence enhanced enzyme reactions and 3 luminescence immunoassays. In most cases, the precision of the ES 300 lay between 2 and 5% in all assays in the concentration ranges of clinical interest. The inter-assay variation was almost identical to the intra-assay precision, which reflects the constancy of reagent quality and machine performance. The correlation between in-house and Enzymun-Test was excellent, even though the slope of the regression line was sometimes far from unity, due to the calibration materials used. ES 300 can be used as a stand alone unit and connected to a host computer. As a "walk-away" machine, it is suitable for laboratories with medium length series. It is a multi-batch analyser capable of taking 12 analytes and a maximal series length of 136 tubes excluding standards and controls. PMID- 8490064 TI - A multi-centre evaluation of the measurement of high density lipoprotein cholesterol by the Reflotron assay. AB - A multi-centre study was undertaken to evaluate the performance of the Reflotron high density lipoprotein cholesterol method in twelve different clinical chemistry hospital laboratories. Results were compared with phosphotungistic acid/Mg2+ and polyethylene glycol/dextran sulphate/Mg2+ precipitation methods, routinely performed in these laboratories. Precision was found to be excellent, for both the day-to-day results (SD = 0.03 mmol/l) and for the overall between laboratory precision (SD = 0.02 mmol/l), measured with control sera. HDL cholesterol concentrations measured with the Reflotron system were about 10% lower than those obtained with the two routine precipitation methods, using different instruments with different cholesterol standardization procedures. PMID- 8490065 TI - Evaluation and performance of the Coulter STKS. AB - The Coulter STKS is a fully automated haematology analyser which quantitatively measures and computes haematological quantities including a full "five-part" differential. The aim of this study was to evaluate whether the Coulter STKS can be used for screening purposes in a non-academic clinic. Results from the haemocytometry part of the apparatus correlated very well with those from the Coulter S Plus IV. Reasonable to good correlations were obtained with the standard manual 100-cell differential for neutrophils, lymphocytes, monocytes and eosinophils. Significantly higher percentages of monocytes were found by microscopic observation than by the STKS. Samples from 1080 patients were analysed on the STKS, and manual differentials were also performed. After revision of discrepancies and with the exclusion of neonatal samples, a good numerical agreement for the "five-part" differential was obtained. The STKS gave 1.8% false negatives, and both diagnostic sensitivity (96.3%) and specificity (83.3%) were high. A false negative rate of 1.9% was found for the indication left-shift, with a predictive value of a negative test of 97.4%. The predictive value of a positive test, however, was only 40.3%. An authorization procedure was implemented to reduce false negative samples. The routine laboratory work load for our differentials can be reduced by up to 70%. The Coulter STKS gave a high number of suspect flags for neonatal samples (75%) and is therefore not suitable for screening neonates. PMID- 8490066 TI - James Joseph Walsh (1865-1942), a forgotten psychiatrist. PMID- 8490067 TI - Thyroid function in bulimia nervosa. AB - Bulimia nervosa is characterized by episodes of binge eating. Bulimic patients have diminished caloric requirements and reduced metabolic rate. Because thyroid function is an important modulator of metabolic rate, we sought to clarify conflicting reports concerning this parameter in bulimic patients. Thyroid indices were examined in 18 bulimics at admission and after 3 weeks of abstinence. Patients had thyroid indices in the normal range at admission but slightly diminished triiodothyronine (T3) compared with control subjects (n = 28). Significant declines in T3 and thyroxine and increases in thyrotropin were noted after 3 weeks of abstinence. At abstinence, T3 was positively correlated with caloric intake, protein, fat, and carbohydrate consumption and inversely correlated with percent ideal body weight. We hypothesize that binge-purge behavior may transiently increase thyroid indices and, consequently, metabolic rate in patients with bulimia nervosa. Furthermore, decreases in T3 following abstinence may be related to diminished caloric consumption or may reflect hypothalamic-pituitary dysregulation in these patients. PMID- 8490068 TI - Color vision deficiencies in the course of acute alcohol withdrawal. AB - Thirty-six male patients with a diagnosis of chronic alcoholism were detoxified and color vision tests were performed on day 4, 11, and 32 of their abstinence on an inpatient basis (Ishihara color plates, Nagel anomaloscope, three color matching tests according to Farnsworth). Of the 36 patients, 47.2% manifested color vision deficiencies. The frequency of congenital red/green defects (11.1%) and a ratio of 3:1 deutan/protan defects showed no significant difference from the incidence in the normal population. In 36.1%, manifest acquired color vision deficiencies were diagnosed. Within the course of withdrawal, a marked improvement of these disturbances could be proved. The degree of the disturbance seems to correlate with the severity of withdrawal symptoms, but seems to be unrelated to acute toxic effects of alcohol, nicotine, or medication. PMID- 8490069 TI - Quantitative EEG in obsessive-compulsive disorder. AB - Electroencephalograms (EEGs) were recorded from 13 unmedicated and nondepressed patients with DSM-III-R obsessive-compulsive disorder (OCD) and from 10 age matched controls. All subjects were also administered the Wechsler Memory Scale Delayed Logical Memory and Delayed Visual Reproduction tests. Quantitative analysis of the EEG revealed lower log absolute power in the delta, beta 1, and beta 2 bandwidths for OCD patients at frontal and right-hemisphere locations. OCD patients displayed greater hemispheric asymmetries in EEG activity based on difference measures of EEG power from homologous electrode pairs, indicative of severe right hemisphere EEG hypoactivity. Standardized measures of hemispheric asymmetry for the beta 2 bandwidth accurately predicted group membership and were correlated both with poorer patient performance on the visual-spatial memory task and better performance on the verbal memory task. OCD patients were significantly impaired on the visual-spatial task, but not on the verbal memory test, relative to controls. PMID- 8490070 TI - Depersonalization after marijuana smoking. AB - Depersonalization and other behavioral and physiological indices were monitored before and after the administration of high- and low-potency marijuana cigarettes and a placebo cigarette in 35 physically and mentally healthy normal volunteers. The cigarettes were administered under double-blind conditions during three visits to the laboratory separated by a minimum of 1 week. Marijuana smoking, but not placebo smoking, was associated with significant depersonalization that was maximal 30 min after smoking the high-potency cigarettes. Other behavioral changes induced by marijuana included disintegration of time sense, sensation of "high," increased state anxiety, tension, anger, and confusion. Respiration, pulse rate, and systolic blood pressure also increased after marijuana smoking. Multiple regression identified temporal disintegration as the most significant predictor of depersonalization. PMID- 8490071 TI - The dexamethasone suppression test and quantitative cerebral anatomy in depression. AB - To determine whether structural brain abnormalities in patients with depression are related to cortisol state, we examined the relationship between the dexamethasone suppression test (DST) and brain magnetic resonance imaging (MRI) in 40 inpatients with severe depression referred for electroconvulsive therapy (ECT). Prior to ECT, 27 (68%) of the patients exhibited nonsuppression on the DST. Frontal lobe volume was negatively correlated with peak post-dexamethasone cortisone (r = -0.37) and was 13% smaller in DST nonsuppressors than suppressors; these findings were no longer significant after adjustments for age, gender, and cranial size. Lateral and third ventricular volumes were also correlated with peak postdexamethasone cortisol (r = 0.34 and 0.33, respectively), but not after adjustments for age, gender, and cranial size. Subcortical hyperintensity was associated with peak postdexamethasone cortisol and was more common in DST nonsuppressors than suppressors. Again these findings were no longer significant after adjustments for age. Finally, longitudinal DST and brain MRI studies in 11 of these patients revealed no changes in regional brain volumes nor in postdexamethasone cortisol up to six months after ECT. However, within individual patients, postdexamethasone cortisol was positively (and significantly) correlated with frontal lobe volume. PMID- 8490072 TI - Autoantibodies to DNA in multicase families with schizophrenia. AB - In an attempt to define the autoimmune status of members of multicase families with schizophrenia, sera of both patients and healthy relatives from 28 such cases were tested for antinuclear antibodies, anti-double-stranded DNA, and anti single-stranded DNA autoantibodies. These autoantibodies were significantly more frequent in both schizophrenic patients and healthy relatives than in normal subjects. Immunoglobulin (Ig) M anti-DNA antibodies were more common in patients, whereas in healthy relatives, IgG anti-DNA antibodies were more common. No significant differences were found between schizophrenic patients and their healthy relatives. The data indicate that an autoimmune process may be involved in the etiology of a subset of patients with schizophrenia. PMID- 8490073 TI - Effect of morning and afternoon naps on mood after total sleep deprivation in patients with major depression. AB - In 30 depressed patients who had responded to total sleep deprivation therapy, morning naps led more frequently to relapses into depression than did afternoon naps. Longer naps were less detrimental than shorter ones, and there was no significant relationship between the effect of a nap on mood and its content of slow-wave-sleep. The amount of the rapid eye-movement sleep, too, was unrelated to clinical nap effects. Thus, some of the current theories on the relationship between sleep and depressive symptomatology are not supported by the data. Our results demonstrate the importance of nap timing, suggesting a circadian variation of propensity to relapse into depression. PMID- 8490074 TI - Comparison of manic switch onset during fluoxetine and trazodone treatment. PMID- 8490075 TI - Is there any acid peptic disease that is refractory to proton pump inhibitors? AB - Non-healing and delayed healing during acid inhibition treatment depend on the extent to which acid and 'non-acid' factors are causative in the particular acid peptic disease, and on the effectiveness and duration of acid suppression. Refractoriness (defined arbitrarily) occurs less often with proton pump inhibitors than with H2-receptor antagonists as the former decrease acid more effectively; H2-receptor antagonist-refractory disease usually responds to treatment with proton pump inhibitors. In Rotherham, 5-10% of duodenal ulcer and gastric ulcer patients are refractory (not healed after > or = 3 months of standard-dose H2-receptor antagonist). In patients with oesophagitis 15% are refractory to high-dose H2-receptor antagonist (for example, 3.2 g cimetidine daily) and 5% to standard-dose proton pump inhibitors (for example, 20 mg omeprazole daily). In controlled clinical trials of patients with refractory duodenal ulcer, healing at 8 weeks with 40 mg omeprazole o.m. vs. continued standard-dose H2-receptor antagonist was 98% vs. 60%; and with 40 mg omeprazole vs. continued high-dose H2-receptor antagonist (2 g + 3 g cimetidine, that is, ultra-refractory disease) was 92% vs. 67%. After healing, in open studies, relapse with maintenance 400-800 mg cimetidine nocte was 45-69% at one year, but 0% with 40 mg omeprazole administered for up to 6.5 years. For 53 patients with refractory gastric ulcer, in an open study, healing with omeprazole 40 mg o.m. occurred in 94% at 8 weeks, and none relapsed on long-term maintenance treatment at this dose. In controlled trials of patients with refractory oesophagitis, healing at 12 weeks with 40 mg omeprazole o.m. vs. high-dose ranitidine (300 mg b.d.) was 90% vs. 47%, and with maintenance 20 mg omeprazole o.m. vs. 150 mg ranitidine b.d., relapse at 1 year was 32% vs. 88%. In conclusion, acid peptic disease refractory to H2-receptor antagonists is uncommon and treatment with proton pump inhibitors is effective. Refractoriness to proton pump inhibitors is rare. PMID- 8490076 TI - Proton pump inhibitors, enterochromaffin-like cell growth and Helicobacter pylori gastritis. AB - In both rodents and humans the development of gastrin-promoted gastric argyrophil enterochromaffin-like cell carcinoids requires the involvement of a genetic factor inherent to multiple endocrine neoplasia syndrome or of type A autoimmune chronic atrophic gastritis. Prolonged severe hypergastrinaemia acting on non gastritic mucosa, as in Zollinger-Ellison syndrome patients, results in diffuse argyrophil enterochromaffin-like cell hyperplasia but, as a rule, does not produce tumours. Combination of chronic atrophic gastritis (mostly related to Helicobacter pylori infection) with hypergastrinaemia frequently causes linear and micronodular hyperplasia of argyrophil cells, whereas carcinoids are exceptional. No tumours or pre-neoplastic lesions have been observed in patients treated long-term with proton pump inhibitors, apart from rare cases in patients with combined Zollinger-Ellison and multiple endocrine neoplasia syndromes. A moderate increase in the incidence of argyrophil cell clustering, with or without hyperplasia, probably results from the parallel evolution of ulcer-associated Helicobacter gastritis into chronic atrophic gastritis. Eradication of H. pylori with a combination of proton pump inhibitors and antibiotics suppresses gastritis and prevents ulcer recurrence. PMID- 8490077 TI - Lansoprazole in the treatment of reflux oesophagitis: a survey of clinical studies. AB - The newly developed proton pump inhibitor lansoprazole has been compared to placebo, ranitidine and with omeprazole in a number of clinical studies in patients with reflux oesophagitis. In three comparative studies against ranitidine, lansoprazole was found to be superior in terms of healing rates and symptom relief. In two studies against omeprazole, no significant difference was found in healing rates, while a Scandinavian study demonstrated more prompt relief from heartburn. Further studies are presently being conducted to evaluate the potential of lansoprazole in long-term treatment of reflux oesophagitis. It is concluded that lansoprazole is a safe, effective therapy for reflux oesophagitis, superior to ranitidine and comparable with omeprazole. PMID- 8490078 TI - Acute treatment of duodenal ulcer: experience with lansoprazole. AB - Clinical experience with lansoprazole in the acute treatment of duodenal ulcer patients has been compared with treatment using placebo, H2-antagonists or omeprazole. Among the various lansoprazole dosage regimens that have been tested, 30 mg daily for 4 weeks appears to be the optimal regimen to relieve pain rapidly and to heal ulceration in up to 90-95% of patients. Lansoprazole tolerability in the short term appears excellent, most adverse effects are trivial and not dose related. Duodenal ulcer relapse after ulcer healing with lansoprazole appears to occur at a rate similar to that observed after treatment with omeprazole or histamine H2-antagonists. PMID- 8490079 TI - Prospective study of the long-term efficacy and safety of lansoprazole in patients with the Zollinger-Ellison syndrome. AB - The long-term safety and efficacy of lansoprazole were studied in 21 patients with Zollinger-Ellison syndrome. The initial maintenance dose was determined by acid inhibition studies. In all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. Patients were treated for a mean of 31 months (range 1-43 months) with all but 4 patients followed for > 18 months. The mean initial dose was 60 mg/day, with 2 patients requiring a twice daily dose and the others a single daily dose. During long-term treatment 6 patients required an increased dosage, 5 within the first year. Long term maintenance doses were reduced in 5 of the 6 patients in whom this was attempted. No changes in serum gastrin concentration, haematological parameters, liver function studies or other biochemical parameters occurred due to lansoprazole. No patient developed a gastric carcinoid tumour while being treated with lansoprazole. These results demonstrate that long-term treatment with lansoprazole is both safe and effective in patients with Zollinger-Ellison syndrome, and suggest that this drug will be useful in such patients. Furthermore, maintenance doses of lansoprazole, determined by the currently recommended method of acute acid titration studies in patients with Zollinger Ellison syndrome, are too high. PMID- 8490080 TI - An open trial of long-term therapy with lansoprazole in patients with peptic ulceration resistant to extended high-dose ranitidine treatment. AB - Forty-two patients with peptic ulceration of the duodenum, stomach or oesophagus, who had not responded to 3 or more months of high-dose treatment with ranitidine (450 or 600 mg/day), were treated with oral lansoprazole at 30-60 mg daily. In 40 patients (95.2%) the ulcers healed within 2-12 weeks. In the remaining 2 patients healing took several months but eventually all ulcers healed. After healing, 40 patients underwent long-term maintenance treatment with 30-60 mg lansoprazole daily for 1-3 years (continuing). During maintenance therapy with lansoprazole, no endoscopically verified relapses occurred when the drug was taken regularly. In 1 patient treatment had to be discontinued because of a drug-related colitis that disappeared soon after treatment had been stopped. There were no significant changes in routine laboratory tests in any patient. Basal serum gastrin concentrations, which were already elevated by the previous high-dose ranitidine treatment (125 +/- 25 pg/ml), rose to four times the normal values after 4 weeks of treatment with lansoprazole (255 +/- 65 pg/ml). Thereafter no further increases in basal serum gastrin concentrations were observed, even after 3 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased slightly during lansoprazole treatment; until now no dysplasia of the enterochromaffin-like cells has been observed. In conclusion, 30-60 mg lansoprazole daily healed ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with 30-60 mg lansoprazole daily was found to be highly effective and safe over the time observed. PMID- 8490081 TI - Safety of lansoprazole. AB - The care with which patients are monitored during clinical trials provides an excellent database to assess the tolerability and safety of drugs. Additional information can be obtained from knowledge of the compound itself, its metabolism and its pharmacological action. Other compounds from the same class can highlight areas that need particular study. All these factors have been used to assess the safety of lansoprazole. Lansoprazole has been administered to 4749 subjects and has been well tolerated. Only 1.2% of patients have been withdrawn from trials because of suspected drug-related events but there was no pattern and no relationship to drug dosage. Diarrhoea (3.2%) and headache (4.7%) were the most commonly reported adverse events. PMID- 8490082 TI - Future prospects for proton pump inhibitors. AB - Future prospects for proton pump inhibitors depend on their efficacy and safety relative to H2-receptor antagonists, the therapeutic standard for acid peptic disorders. As safety concerns diminish, efficacy considerations become more important as these may pertain to cost effectiveness. Comparative, controlled trials show that omeprazole and lansoprazole are somewhat more effective than H2 blockers in healing duodenal and gastric ulcers, providing faster relief of symptoms. Relapse after cessation of therapy is similar between the two classes. The proton pump inhibitors are substantially more effective in healing lesions and relieving symptoms in patients with reflux oesophagitis, and are particularly effective in cases that have failed to heal after 12 weeks of treatment with H2 blockers. Relapse rates of oesophagitis are significantly less with prolonged treatment with omeprazole than ranitidine. A proton pump inhibitor combined with amoxicillin is less effective than triple therapy with antibiotics and bismuth in eradicating Helicobacter pylori infections, but is more convenient and associated with fewer side-effects. Efficacy might be improved by more optimal dosing regimens. Prospects for reversible proton pump inhibitors depend on the balance between their theoretical advantages and their acid inhibition profile which, at present, closely resembles that of H2-blockers. PMID- 8490083 TI - [A simple test procedure for detection of micro-bubbles in extracorporeal blood circulation]. AB - A new contrast medium for the ultrasonic examination of the human heart was recently approved by the German medical authorities. It has proved useful for investigating the sensitivity of air detectors in detecting microbubbles measuring only a few microns in the extracorporeal line. Although the contrast medium, originally intended to be injected undiluted into the human blood circulation, was considerably diluted, microbubbles were detected by the ultrasonic air detector far below the danger limit. PMID- 8490084 TI - [ISFET-pH recording probe for vaginal pH monitoring]. AB - The measurement of pH is increasingly being used as an additional or prophylactic diagnostic method in gynecology. In this paper a new measuring set-up for this purpose is described. The special rod-shaped probe contains an ISFET pH sensor and a miniaturized reference electrode. Initial experimental results of in vivo applications are discussed. PMID- 8490085 TI - [A program for control of competitive stimulation for inducing evoked potentials]. AB - The Standard method of eliciting event-related potentials, the "oddball" paradigm, is insufficient as the sole technique for more differentiated problems. We therefore developed a more complex yet, in terms of variation of the stimuli, more flexible, method-competitive stimulation. This method also employs a two stimuli paradigm, but uses independently delivered identical target and non target stimuli with spatial separation. Since this technique requires special control mechanisms for the delivery of the stimuli, in particular with respect to the observance of time intervals between consecutive stimuli, we designed a software control program for the stimulation. This program can be run on any PC and permits great flexibility in the choice of the stimulus parameters and peripheral stimulating systems. PMID- 8490086 TI - [Fretting in modular design implant systems]. AB - Fretting is a problem of load-bearing implants (hip, knee) especially when modular in design and employing different materials. In contrast, fretting has not yet been observed in dental implants. In the case of ceramic femoral heads and cups (e.g. BIOLOX) no problems with fretting have so far been reported. The state-of-the-art is discussed and assessed. PMID- 8490087 TI - The emerging genetic theories of unstable DNA, uniparental disomy, and imprinting. AB - Usually, genetic diseases segregate in a stable, predictable fashion throughout a family. For many inherited disorders, a mutation at the DNA level has been characterized, and prenatal diagnosis is available. Recently, however, the dogma of traditional mendelian inheritance has been challenged by the discovery of new patterns of gene segregation and expression. Unstable DNA segments varying in size have been associated with both fragile X syndrome and myotonic dystrophy and can now be diagnosed by direct DNA analysis. Uniparental disomy, the inheritance of both members of a chromosome pair from one parent, has been documented in autosomal and X-linked recessive diseases. Imprinted genes, the expression of which is dependent on the parent of origin, are being increasingly identified, especially in syndromes with abnormalities of growth. In the near future, the number of prenatally diagnosed disorders will expand as tests for unstable DNA, uniparental disomy, and imprinting become widely available. PMID- 8490088 TI - Fetal size and growth. AB - Prior to the introduction of ultrasound, Nagele's rule was the primary method for determining gestational age. Ultrasound has enabled a more accurate estimation of gestational age, allowing for improved detection of the fetus who is small for gestational age and reducing the number of women who are diagnosed as being overdue. The latest biometry charts that can be used for assessment of growth and dating are reviewed. It has long been recognized that a small or growth-retarded fetus has much greater short-term morbidity and mortality compared with its normal counterpart. More recently, the long-term sequelae of this condition are being recognized, illuminating the importance of the prevention and prediction of pregnancies with fetal growth problems. By focusing on better education and nutrition to prevent pregnancies at risk of becoming growth retarded and by using ultrasound to predict and manage these cases, we can improve the outcome for this group of patients. PMID- 8490089 TI - Doppler studies of deteriorating growth-retarded fetuses. AB - Intrauterine growth retardation continues to be one of the major problems in obstetrics and still greatly contributes to perinatal mortality and morbidity. This paper reviews the role of Doppler ultrasonography in the antenatal assessment of fetuses with intrauterine growth retardation. Recent developments in this field are described with particular emphasis on the pathophysiologic background of the hemodynamic modification of fetuses with intrauterine growth retardation. Doppler ultrasonography allows the prediction of the development of intrauterine growth retardation in selected populations and the identification among a population of small-for-gestational-age fetuses, those really at risk of unfavorable outcome. Finally, the modifications occurring after the establishment of the growth retardation with the progression of fetal deterioration are described in an attempt to clarify the natural history of this condition. To this end, the longitudinal changes of Doppler indices of placental vessels, fetal arterial vessels, fetal heart, and venous circulation are described, and their complex interrelationship is analyzed. The knowledge of these mechanisms may be useful in deciding the timing of delivery. PMID- 8490090 TI - Ultrasound screening for fetal structural anomalies. AB - Ultrasound prenatal diagnosis of structural anomalies has become almost a separate branch of obstetrics. The advantages of performing ultrasound in pregnancies at high risk for fetal structural anomalies are clear. Patients and the news media have placed ever-increasing expectations on persons performing diagnostic ultrasound of the fetus. However, the benefits and cost-effectiveness of routine ultrasound screening during pregnancy remain unclear. This review focuses on three controversial topics related to the use of screening ultrasound for fetal structural anomalies: routine ultrasound screening, the four-chamber view, and amniocentesis versus ultrasound for detection of neural tube defects. PMID- 8490091 TI - Amniocentesis and chorionic villus sampling. AB - Amniocentesis performed at 16 to 18 weeks' gestation has been the gold standard approach for prenatal cytogenetic diagnosis. Over the past few years, large collaborative studies on chorionic villus sampling have confirmed the safety and efficacy of chorionic villus sampling as a viable alternative for women seeking prenatal diagnosis. While the expanding experience with chorionic villus sampling has answered questions regarding the safety of the transabdominal approach, it has also raised questions concerning possible associations with limb abnormalities, its usefulness in multiple gestations, and the clinical significance of confined placental mosaicism. These issues, as well as the technical and gestational age limitations of chorionic villus sampling, have led many investigators to study the technical feasibility, safety, and accuracy of amniocentesis performed in the first trimester or early second trimester. While this approach appears both safe and efficacious, there are concerns regarding orthopedic abnormalities and the reliability of first-trimester amniotic fluid acetylcholinesterase and alpha-fetoprotein levels in the diagnosis of neural tube defects. PMID- 8490092 TI - Cordocentesis. AB - Access to the fetal circulation via cordocentesis has resulted in many advances in both prenatal diagnosis and fetal therapy over the past decade. In this review, current research in the assessment and treatment of erythrocyte isoimmunization and fetal infection by fetal blood sampling, as well as the role of cordocentesis in the evaluation of fetal platelet abnormalities, intrauterine growth retardation, fetal thyroid function, and genetic investigation, are discussed. Finally, a brief review of complications and loss rates relating to this procedure is given. PMID- 8490093 TI - Current management of unexplained infertility. AB - During the last decade, numerous studies have evaluated the effectiveness of various treatments for unexplained infertility. Few studies employ a design that allows for appropriate comparison with an untreated control group. This article reviews the efficacy of clomiphene citrate, human menopausal gonadotropin, intrauterine insemination, superovulation with intrauterine insemination, and gamete intrafallopian transfer in the treatment of unexplained infertility. Treatment for patients with unexplained infertility with superovulation or gamete intrafallopian transfer is promising, but the incremental contributions of intrauterine insemination, superovulation, or gamete intrafallopian transfer beyond untreated controls await appropriately designed trials. When counseling patients regarding treatment options, both the expected increase in cycle fecundity and treatment expense should be considered. PMID- 8490094 TI - The use of growth hormone treatment for ovulation induction. AB - The use of growth hormone in enhancing the ovarian response to gonadotropins is reviewed. The data support the utility of growth hormone in reducing the effective gonadotropin dosage and in most cases, increasing the ovulatory quota. PMID- 8490095 TI - Transcervical tubal cannulation and salpingoscopy in the treatment of tubal infertility. AB - Transcervical tubal cannulation and salpingoscopy are two recent techniques used for the evaluation of tubal patency and pathology. Selective tubal cannulation cannot determine the nature of the obstructive process, although it does allow for the demonstration of potential tubal patency. This may be important in deciding whether therapies requiring tubal patency may be used in specific clinical situations. Because currently there are no controlled studies in the literature evaluating this technique, the therapeutic value of the procedure must be considered unproven at this time. Salpingoscopy gives more detailed information concerning the tubal mucosa. The identification of specific tubal lesions has been described with this modality. The predictive value of salpingoscopy in cases of severe anatomic distortion, ie, fibrous obliteration, seems obvious. However, its predictive value in the presence of more subtle lesions needs to be studied further because its role as a therapeutic modality is as yet undefined. PMID- 8490096 TI - Reassessment of male-factor infertility, including the varicocele, sperm penetration assay, semen analysis, and in vitro fertilization. AB - Evaluation of the male factor in infertility is becoming increasingly important as new diagnostic techniques and therapeutic options become available. Varicoceles are among the most common treatable cause of male infertility. Varicoceles are present in 10% to 20% of all males but are found in as many as 30% to 40% of men who present to an infertility clinic. Of men who have treatment for varicoceles, 50% to 75% will show some improvement in semen quality, and 30% to 40% will initiate a pregnancy. We review some controversial issues related to the diagnosis and treatment of varicoceles. In vitro fertilization, originally developed for the female with irreversible tubal damage, is now being evaluated as a possible therapy for severe male-factor infertility that has failed to respond to routine surgical or medical treatment. In vitro fertilization for the oligospermic male, however, is further complicated by the fact that men with poor sperm production frequently have poorly functioning sperm as well. Consequently, we discuss the value of the sperm penetration assay, with and without enhancement techniques to prospectively evaluate couples entering in vitro fertilization programs. We also discuss the role of strict criteria for determination of sperm morphology and quantitation of leukocytospermia in the evaluation of the infertile male. Finally, evaluation of the predictive value of "failure to fertilize" at in vitro fertilization for future in vitro fertilization success is discussed. PMID- 8490097 TI - Current status of immunologic recurrent pregnancy loss. AB - Normal mammalian pregnancy is confronted with a great number of self (autoimmune) and foreign (alloimmune) antigens that modulate the immune system of the mother. When maternal immune response is affected, recurrent pregnancy loss can result. Recurrent pregnancy loss affects 2% to 5% of reproducing couples. Half of these failures can be explained by genetic, hormonal, infectious, and anatomic factors. Eighty percent of the unexplained failures are proposed to have an immunologic cause. HLA typing, mixed lymphocytotoxic antibody tests, mixed lymphocyte culture reactions, lupus anticoagulant tests, and antiphospholipid antibody determination are methods used to study and differentiate between auto- and alloimmune response. Experimental therapies, including leukocyte immunization, seminal plasma suppositories, intravenous immunoglobulin, aspirin and prednisone, and heparin, have been tried to manage this condition. Results of randomized placebo controlled clinical trials will aid in the choice of treatment for recurrent pregnancy loss. New assays to diagnose auto- and alloimmune factors in recurrent pregnancy loss are being investigated. PMID- 8490099 TI - Prenatal diagnosis. PMID- 8490098 TI - Endoscopic treatment of ectopic pregnancies. AB - Laparoscopic management is now the gold standard treatment of ectopic pregnancy. It can be performed using different procedures such as salpingotomy and salpingectomy, or it can be combined with methotrexate injection. On the other hand, nonsurgical treatment is available. The authors discuss technique results and indications of these various therapeutic techniques. PMID- 8490100 TI - Fertility and infertility. PMID- 8490101 TI - Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69. AB - In many immunoinflammatory diseases, macrophages, by producing interleukin-1 (IL 1) and tumor necrosis factor alpha (TNF alpha), stimulate protease secretion in fibroblasts, thus contributing to tissue destruction. Monocyte/macrophage activation is prompted by soluble factors released by activated T cells as well as by cell-cell contact. Indeed, previous studies have shown that monocytes exposed to paraformaldehyde (PFA)-fixed, activated T cells produced high amounts of IL-1 beta. In this report, we used the T cell line HUT-78 to further characterize the T cell factor(s) responsible for monocyte activation by cell cell contact. After subcellular fractionation, most of the activity was found in the cellular membrane fraction of PHA/PMA-stimulated HUT-78 cells, and proved to be due to glycoproteins, following trypsin digestion and tunicamycin treatment. HUT-78 cells acquired the capacity to stimulate monocytic cells after as little as 1h of stimulation. De novo protein synthesis was required for the expression of the IL-1 beta inducing factor, as shown by cycloheximide treatment. When membrane proteins of PHA/PMA-stimulated HUT-78 cells were separated on SDS polyacrylamide gel, a peak of stimulatory activity was observed at Mr--25-35 x 10(3). By using specific cytokine inhibitors or blocking mAbs, we ascertained that cell-associated cytokines (IL-1, IL-2, IFN gamma and GM-CSF) were not involved in monocyte activation by cell contact. Anti-CD2 and -CD11a (LFA-1) mAbs partially blocked IL-1 beta production by -25% and -35%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490102 TI - One and two-level regulation patterns affecting NF-kappa B mRNA and nuclear NF kappa B activity after treatment with TNF-alpha, IFN-gamma and IL-4. AB - The transactivating nuclear factor NF-kappa B is believed to be important in the pathophysiology of many cellular systems and mainly during HIV infection. kappa B activation has also been implicated in the process of differentiation as a cell progresses to a more mature and functional stage. As induction of differentiation equals growth retardation we undertook this study in order to establish the role of NF-kappa B in cell growth and maturity. Thus we employed the well described HL 60 cellular system that expresses constitutively basal amounts of NF-kappa B and is susceptible to NF-kappa B induction by various biological or chemical agents. We also used known inducers of differentiation like TNF-alpha, IFN-gamma and IL-4 that interact via their corresponding surface receptors found on HL-60 cells. We first studied by Northern analysis the possible correlation between c-myc and NF kappa B precursor (p105) mRNA. We witnessed that all three cytokines were able to confer proliferative senescence and down-regulate concomitantly c-myc and NF kappa B mRNA levels, events chronologically in accord with induction of differentiation as assessed by the induction of HLA-DR surface antigens. It is known that TNF-alpha is capable of inducing nuclear kappa B activity in HL-60 as the cells progress to a more mature stage. Therefore we examined whether the other two cytokines could do the same during the time they lead the cells to a differentiated phenotype. If this was the case, nuclear activation of NF-kappa B should be obtained by the same factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490103 TI - Protein kinase C regulates TNF-alpha production by human monocytes. AB - Tumor Necrosis Factor alpha (TNF alpha) is a cytokine mediator that is produced primarily by activated monocytes/macrophages in response to endotoxin/lipopolysaccharide (LPS) as well as other stimuli. The second messenger systems that regulate the synthesis and release of TNF alpha are not clearly defined. In the present study, the role of protein kinase C (PKC) in the production of TNF alpha was investigated in human peripheral blood monocytes stimulated with either LPS or zymosan. Two broad spectrum protein kinase inhibitors (staurosporine and K252a) and two PKC specific inhibitors (calphostin C and chelerythrine), were used as probes to delineate the involvement of PKC in the production of TNF alpha. The results indicate that inhibition of PKC diminished LPS- or zymosan- induced TNF alpha production in a concentration dependent manner. The IC50 values for the inhibition of TNF alpha production were 0.2 nM for staurosporine, and 20 nM for K252a, Calphostin C and chelerythrine. Furthermore, long term PMA treatment of these cells (to abrogate PKC-mediated responses) resulted in a significant reduction of stimuli-induced TNF alpha production. LPS and zymosan also induced an increase in membrane associated PKC activity in human monocytes, which could be inhibited by pretreatment of the cells with calphostin C. Finally, western blot analysis with PKC isoform-specific antibodies demonstrates that the alpha and xi are the predominent isoforms expressed in human monocytes. These data strongly suggest that an initial step in TNF alpha production by human monocytes challenged with physiological stimulants, such as LPS and zymosan, involves a PKC-dependent mechanism. PMID- 8490104 TI - Interleukin-2 and soluble interleukin-2 receptor levels in children with active pulmonary tuberculosis and atypical mycobacterial adenitis. AB - Interleukin-2 (IL-2) level was measured in sera and in supernatants of Purified Protein Derivatives of Tuberculin (PPD) stimulated peripheral blood mononuclear cells (PBMC) cultures from children with active primary pulmonary tuberculosis (TB), or adenitis caused by mycobacteria of the group Mycobacterium avium, intracellulare, scrofulaceum (MAIS). The control groups included BCG vaccinated children (BCG) and children with negative skin test to PPD (NST). High mean IL-2 level was exclusively found in sera of mild TB patients (MTB), and not in sera of MAIS infected or BCG vaccinated children. The IL-2 level increased even more in MTB during treatment. In severe TB (STB) the IL-2 level was not elevated before treatment, but increased also during treatment. IL-2 production in supernatants of PPD stimulated PBMC cultures was increased in MTB as well as in MAIS and BCG subjects. Further, soluble IL-2 receptor (sIL-2R) levels were measured in the different groups of children. With the exception of the STB group, there was otherwise no significant increase of the receptor in the sera levels between groups. During treatment the sIL-2R levels decreased in MTB as well as in STB. A slight but non significant augmentation was found in the supernatants of PBMC cultures stimulated with PPD. This work suggests, along with other referable studies, that IL-2 and sIL-2R levels are inversely modulated by the disease. Indeed, the IL-2 seems to increase in MTB comparatively to NST children, and in treated TB comparatively to non treated TB children. On the other hand, the sIL 2R level was found to decrease in TB under treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490105 TI - Human interleukin-6: detection of 10 attomoles by colorimetric sandwich ELISA using immunopurified polyclonal anti-IL-6 antibodies. AB - A convenient and sensitive sequential sandwich colorimetric ELISA test was established for quantitating IL-6 in culture supernatants or in serum. Immunopurified HRP-labelled rabbit Fab' fragment was used as the tracer and IgG coated microtiter plate as the capture antibody. The limit of detection was as low as 10 attomoles of analyte (2.5 pg/ml). Unglycosylated recombinant IL-6 and the natural glycosylated cytokine were recognized equally. In addition, IL-6 measurements were unaffected by the presence of various cytokines and assay sensitivity was only slightly reduced in the presence of undiluted serum samples. The technique was applied to the study of in vitro IL-6 production from activated monocytes and to the in vivo determination of IL-6 in various pathological states. PMID- 8490106 TI - CD3-stimulated Jurkat T cells mediate IL-1 beta production in monocytic THP-1 cells. Role of LFA-1 molecule and participation of CD69 T cell antigen. AB - In this study we investigated the T cell signals required for monocyte activation. We used an in vitro co-culture system involving two human cell lines: Jurkat T cells and THP-1 monocytes. Monocyte activation was monitored by measuring IL-1 beta production, whereas IL-2 secretion reflected Jurkat activation. We showed that CD-3 -stimulated Jurkat cells delivered an IL-1 inductive signal to THP-1 cells through a cellular contact which was independent of THP-1 Fc receptors cross-linking. Stimulation of IL-1 beta production did not appear to require lymphokine secretion by T cell since a lymphokine defective mutant of Jurkat cell was able to deliver the stimulatory signal. The LFA-1 molecule was clearly shown to participate in the cooperation process, but its role was likely to be restricted to mediating initial adhesive interaction rather than to transducing the IL-1 -inductive signal. Interestingly, the co-culture stimulated by (Fab')2 fragments of CD3 mAb displayed an enhanced IL-1 beta production without any increase of IL-2 secretion. This result indicated that Jurkat cells could stimulate THP-1 cells even when they were only partially activated. The kinetics and conditions of IL-1 beta production called our attention to the early T cell activation antigen CD69. We then showed that CD69 mAb interfered with transmission of the IL-1 inductive signal (40-50% inhibition of IL-1 production). Our results are suggestive of a new role for CD69 molecule intervening in the T lymphocyte-dependent monocyte activation process. PMID- 8490107 TI - Immunomodulator polysaccharides: chemistry, disposition and metabolism. PMID- 8490108 TI - Pharmacokinetic study of a tripeptide HIV-1 protease inhibitor, KNI-174, in rats after intravenous and intraduodenal administrations. AB - Recently, as a new type of anti-AIDS drug, an HIV-1 protease inhibitor, KNI-174, has been synthesized; it shows a potent and selective HIV-1 protease inhibitory activity in vitro. In this study, we developed an HPLC assay system for KNI-174 in rat plasma and examined the pharmacokinetics of KNI-174 in rats using this assay method after both intravenous (i.v.) and intraduodenal (i.d.) administrations to obtain the disposition characteristics and bioavailability of this new anti-AIDS drug. This HPLC assay method is specific to KNI-174 and the standard curve was linear from 0.02 to 30 micrograms ml-1 plasma. After i.v. administration, 10.0 mg kg-1, KNI-174 disappeared from the rats' plasma in a three-exponential decay. The mean terminal elimination half-life, t1/2 lambda z, was 3.97 +/- 0.19 (S.E.) h, the total body clearance, CLtot, was 9.53 +/- 1.08 ml min-1 and the distribution volume at steady state, Vd,ss, was 7070 +/- 960 ml kg 1. In the case of the i.d. administration, 10.0 mg kg-1, the mean peak plasma concentration, Cmax, and the peak time, tmax, were 0.196 +/- 0.076 micrograms ml 1 and 0.444 +/- 0.193 h, respectively. The bioavailability of KNI-174 till infinity, BA(0-infinity), was 5.37 per cent. Because the IC50 of KNI-174 against HIV-1 in PHA-PBM was 138 ng ml-1, the time needed for maintaining the concentrations above IC50 after a single i.d. administration of KNI-174 is estimated to be 0.350 +/- 0.184 h. PMID- 8490109 TI - Influence of food on the disposition of the monoamine oxidase-A inhibitor brofaromine in healthy volunteers. AB - The effect of food on the bioavailability of brofaromine hydrochloride was investigated in a randomized cross-over study. Eight healthy male volunteers were given single peroral doses of 75 mg brofaromine hydrochloride after overnight fasting or a fat- and protein-rich breakfast. Mean (+/- SD) areas under the plasma concentration-time curves (AUC) were 9.66 (2.35) mumol l-1 h when given to the fasted volunteers and 11.82 (3.78) mumol l-1 h (p = 0.0413) when given after a substantial breakfast. Mean (+/- SD) maximum plasma concentrations (Cmax) were 0.71 (0.13) mumol l-1 when given to the fasted volunteers and 0.85 (0.22) mumol l 1 (p > 0.05) when given after breakfast. Thus, both the average AUC and Cmax were increased by approximately 20 per cent when brofaromine hydrochloride was given with food. The times when Cmax was reached (tmax) as well as the elimination half lives were not influenced by concomitant intake of food. The tolerability was the same whether brofaromine was given before or after food in healthy volunteers. The slight effect of food on the bioavailability of brofaromine should be of little therapeutic consequence because of the observed wide inter-subject variability of the plasma levels. PMID- 8490110 TI - Pharmacokinetics of D-propranolol following oral, intra-arterial and intraportal administration: contrasting effects of oral glucose pretreatment. AB - Several research groups have reported that in man the oral administration of propranolol with food leads to a marked increase (about 50 per cent) in the area under the plasma concentration-time curve (AUCpo) of this well absorbed and highly metabolized drug. An acute change in hepatic metabolic enzyme activity has been postulated as one of the mechanisms which could be responsible for this observed 'food effect'. The administration of simple carbohydrates such as glucose and fructose has been documented to influence hepatic drug metabolism. Therefore, in the present study, the effect of oral glucose (4 g kg-1 as a 50 per cent aqueous solution) on the disposition kinetics of d-propranolol was examined in male Sprague-Dawley rats (8 to 9 per group). Oral glucose treatment caused a statistically significant decrease (50.4 +/- 12.3 vs 36.6 +/- 15.2 min micrograms ml-1; p < 0.05) in the AUCpo of propranolol when this drug was given by oral intubation (10 mg kg-1). This glucose treatment also caused the apparent mean residence time of propranolol after an oral dose to increase from 0.70 +/- 0.08 h to 1.79 +/- 0.29 h (p < 0.05), but did not change its rate of elimination (suggesting collectively a decreased apparent intrinsic clearance and prolonged drug absorption). In a second study, the same oral glucose treatment was demonstrated to have little impact on the steady state concentrations of propranolol when this drug was infused intraarterially at a constant rate. This confirms that the systemic clearance of propranolol is influenced minimally by the glucose treatment. In a third study, propranolol was infused at a constant rate into the portal vein (pyloric vein infusion) bypassing the processes of intestinal metabolism and absorption (i.e. to remove these sources of variability associated with oral administration). Under these conditions, no significant changes in AUC or apparent mean residence time were observed for the two propranolol doses studied (10 mg kg-1 and 5 mg kg-1). We conclude that the oral glucose and oral propranolol interaction appears to be due to an alteration in the input process before drug enters the liver. Furthermore, this experimental series suggests that studies combining accurate assessments of systemic clearance (constant rate intra-arterial infusion studies), intrinsic hepatic clearance (pyloric vein infusion studies), and oral administration supplemented with necessary protein binding studies may be used together to characterize the mechanism responsible for drug-nutrient and drug-drug interactions. PMID- 8490111 TI - Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of bumetanide. AB - The pharmacokinetics and pharmacodynamics of bumetanide were evaluated after intravenous (i.v.) administration of the same total dose of bumetanide in different lengths of infusion times, 10 s (treatment I), 1 h (treatment II), and 4 h (treatment III) to rabbits. The fluid loss in urine was immediately replaced volume for volume with i.v. infusion of lactated Ringer's solution. Some pharmacokinetic parameters of bumetanide were infusion time-dependent and it might be due to the saturable metabolism of bumetanide. For example, the mean values of CL (13.6, 25.3 vs 18.2 ml min-1 kg-1), MRT (9.70, 10.6 vs 21.8 min), Vss (128, 217 vs 378 ml kg-1), and CLNR (2.71, 9.24 vs 6.44 ml min-1 kg-1) increased when the same dose of bumetanide was infused in 1 h or 4 h. However, the mean values of t1/2, and CLR were not significantly different among three treatments. The diuretic effects (urine outputs and urinary excretions of sodium and chloride) increased significantly in 1 and 4 h of infusion although the total amounts of urinary excretion of unchanged bumetanide were 21.8 and 20.5 per cent lower in treatments II and III, respectively, when compared with the value in treatment I; the mean values of 8-h urine outputs were 373, 922, and 1030 ml for 10s, 1 h, and 4 h of infusion, respectively, and the corresponding values for 24 h sodium excretions were 49.0, 82.8, and 121 mmol, and for chloride were 47.5, 71.1, and 114 mmol. It could be due to the higher diuretic efficiencies in treatments II and III. Plasma concentrations of bumetanide, and hourly urine outputs and hourly urinary excretion rates of bumetanide, sodium, potassium, and chloride during the apparent steady state (between 1 and 4 h) in the 4 h infusion study were fairly constant. PMID- 8490112 TI - Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method. AB - Twenty-four young healthy volunteers received a single dose of metformin 500 mg (Glucophage, Nordic Laboratories, Canada) in tablet form. Plasma concentrations were determined by HPLC in samples collected prior to and 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12, 15, 18, 24, and 30 h after dosing. Mean (+/- SD) Cmax was 682.1 (160.6) ng ml-1 at a mean (+/- SD) tmax of 2.4 (0.93) h. Overall elimination was monoexponential with a mean (+/- SD) half-life of 3.16 (0.47) h. We conclude that metformin is rapidly absorbed from this formulation and is also rapidly eliminated. Extrapolation to steady state predicts that equilibrium will be reached within 24 h. PMID- 8490113 TI - Kinetic modeling of liposome degradation in blood circulation. AB - The aim of this study is to develop a kinetic model for the quantitative evaluation of, and to examine dose dependency in liposome degradation in blood circulation in vivo. Multilamellar liposomes labeled with 3H-inulin were administered intravenously into rats and the time courses of blood concentration and urinary excretion of 3H-inulin were measured. The dosages of liposomes were fixed at 1, 5, and 100 mumolPCkg-1. Remarkable saturation was found in the time courses of both blood concentration and urinary excretion. Then a kinetic model for the degradation of liposomes in blood was developed, assuming that the degradation follows the first order rate process for each dose. The model fitted the observed time courses of excreted 3H-inulin well, and dose dependency could be observed in the rate constants for liposome degradation, which are more sensitive than urinary excretion of 3H-inulin. The degradation rate constant correlated well with the uptake rate constant, which suggests the same underlying mechanism for both uptake and degradation. These results indicate the usefulness of kinetic modeling in the quantitative evaluation of liposome degradation in blood circulation in vivo. PMID- 8490114 TI - Effect of pirenzepine on the N-demethylation of D(-)ephedrine and ethylmorphine by rabbit liver microsomes. AB - The possible interaction of pirenzepine with the mixed-function oxidases obtained from phenobarbital-pretreated rabbit microsomes was examined in vitro. Under experimental conditions that did not lead to its own N-demethylation, the drug inhibited the microsomal oxidase systems responsible for the N-demethylation of D(-)ephedrine and ethylmorphine. Kinetic studies showed that pirenzepine inhibited the metabolism of both drugs in a competitive manner. The results indicated that the observed pirenzepine stability to the hepatic N-demethylating system is not a result of low affinity of the drug to the system. PMID- 8490115 TI - Autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of medical morbidity in the United States that affects one-half million persons and accounts for ESRD in about 10% of the chronic dialysis population. In addition to its effects on the kidney, the disease has important manifestations in the cardiovascular system (aneurysms, hypertension) and the gastrointestinal tract (hepatic cysts). Clinically important renal complications can develop as the disease progresses that require specialized attention, such as urinary tract infection, pain, and nephrolithiasis. The underlying cellular defect that causes ADPKD has eluded investigators thus far, but abnormalities in cellular proliferation, the tubular basement membrane, and cell fluid secretion appear important in pathogenesis. Factors that mediate progressive interstitial fibrosis and failure of renal function are undefined, although rigorous control of blood pressure appears to be an important therapeutic measure. Recent advances in molecular biology have localized the abnormal gene to chromosome 16 in 90% of families, making early genetic screening of asymptomatic family members possible in many cases. A positive diagnosis may have important effects on employment status, as well as health insurance, so that family members sometimes refuse to be assessed for the presence of the disease. Because of such complex social factors, counseling of an asymptomatic individual by his or her physician is required when considering the use of screening tests for ADPKD. Inadequate patient education may still represent an impediment to early detection, genetic counseling, and timely treatment of disease complications. PMID- 8490116 TI - Elevated blood pressure profile and left ventricular mass in children and young adults with autosomal dominant polycystic kidney disease. AB - Twelve children (< 15 yr) and 12 young adults with autosomal dominant polycystic kidney disease (ADPKD) confirmed by ultrasonography and 24 nonaffected individuals matched for age, sex, and body surface area were examined with ambulatory blood pressure monitoring and echocardiography. All patients and controls had normal renal function (median serum creatinine, 0.85 mg/dL; range, 0.5 to 1.1). In children, daytime and nighttime blood pressures were not significantly different from those of controls; the median left ventricular mass index (in grams per square meter) was higher in patients (66.6 g/m2) than in controls (61.3 g/m2; P < 0.002), although all values remained within the normal range. In young adults with ADPKD, mean arterial blood pressure was significantly higher than that in controls both during daytime (98.3 mm Hg; range, 74 to 126 versus 90.6 mm Hg; range, 73 to 116; P < 0.006) and during nighttime (83.2 mm Hg; range, 66.5 to 125 versus 79.0 mm Hg; range, 63 to 91; P < 0.05). In parallel, the median left ventricular mass index was significantly higher in young adults (81.8 g/m2; range, 62 to 174 versus 64.3 g/m2; range, 52 to 102; P < 0.02). The results document that ambulatory daytime and nighttime blood pressures and left ventricular mass indices are higher in asymptomatic carriers of the ADPKD trait compared with controls, although most values are still within the normal range. PMID- 8490117 TI - Heterogeneous nature of renal lesions in type II diabetes. AB - The nature of renal damage in patients with type II diabetes remains unclear. This study was directed to evaluate pathologic changes in 52 patients affected by type II diabetes with overt clinical nephropathy by conventional and morphometric techniques. The duration of diabetes ranged from 6 to 384 months, urinary protein excretion ranged from 0.9 to 9.2 g/24 h, and serum creatinine ranged from 0.9 to 9 mg/dL. Specimens were examined semiquantitatively by light microscopy, immunofluorescence, and electron microscopy. Glomerular tuft cross-sectional area was measured by a versatile computer system. Pathologic examination revealed three distinct patterns arbitrarily defined as Classes 1, 2, and 3. Class 1 included 19 patients with typical changes of diabetic nephropathy characterized by a high score of glomerulosclerosis (mean score, 2.1), marked glomerular hypertrophy (23,632 microns2), and arteriolar hyalinosis (mean score, 2). There was a positive correlation between glomerulosclerosis and arteriolar hyalinosis scores (P < 0.05). Class 2 included 16 patients showing chronic and aspecific changes. As compared with Class 1 patients, these patients had less glomerulosclerosis (mean score, 1.3) and less arteriolar hyalinosis (mean score, 0.8) but more severe ischemic glomerular lesions (mean score, 1.4) and arteriosclerosis (mean score, 2). Class 3 included 17 patients showing glomerular disease superimposed on diabetic glomerulosclerosis. There were no differences in age, mean duration of diabetes, renal function, urinary protein excretion, and mean arterial pressure among the three classes of patients. This study indicates that renal lesions in patients with type II diabetes manifest in a quite heterogeneous fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490118 TI - Racial variation in human leukocyte antigen frequency in insulin-dependent diabetic nephropathy. The South-Eastern Organ Procurement Foundation. AB - Black patients with insulin-dependent diabetes mellitus are at increased risk for the development of diabetic nephropathy compared with white patients. To determine if genetic differences associated with the HLA system account for racial variation in insulin-dependent diabetes mellitus-induced nephropathy, serologically defined HLA phenotypes from renal transplant recipients and donors in the South-Eastern Organ Procurement Foundation database from 1982 to 1986 were analyzed. Renal transplant recipients (N = 1,531) with insulin-dependent diabetes mellitus-induced renal failure as the cause of ESRD (patients) were compared with 4,506 race-matched, nondiabetic cadaveric kidney donors (controls). Log-linear models were used to assess the relationship between insulin-dependent diabetes mellitus-induced renal failure and prevalence of each HLA phenotype. Bonferroni adjustments of P values were used to correct for multiple comparisons. A comparison of HLA frequencies in patients with insulin-dependent diabetes mellitus-induced renal failure demonstrated the presence of racial differences beyond those normally present between the black and white populations. Blacks, compared with whites, had increased frequencies of HLA-B62 (odds ratio [OR] black:white, 6.13:1.97; P < 0.02) and HLA-DR9 (OR black:white, 4.82:1.57; P < 0.008) and decreased frequencies of HLA-A1 (OR white:black, 1.56:0.8; P < 0.008) and HLA-DR3 (OR white:black, 4.9:2.82; P < 0.004). These results suggest that differences in HLA frequency may account, in part, for the observed racial variation in incidence of diabetic nephropathy. In addition, several antigens in positive and negative association with diabetic nephropathy were identified within each race. PMID- 8490119 TI - Tissue concentration and urinary excretion pattern of sulfofluorescein by the rat kidney. AB - In order to find a fluorescein analog that is excreted in a way similar to p aminohippurate (PAH) and is suitable to register excretion into the urine and also to monitor continuously the concentration within cortical tissue, the interference of fluorescein, sulfofluorescein (SF), and fluorescein-5(6) sulfonate with the contraluminal transport systems of PAH, succinate, and sulfate and with the luminal transport system of sulfate and lactate was evaluated. All three substances exerted a strong inhibitory potency against contraluminal PAH uptake (apparent Ki, 0.06 to 0.1 mmol/L) and also showed a moderate to small inhibitory potency against contraluminal sulfate transport (apparent Ki, 0.7 to 5.3 mmol/L). None of the three substrates interacted with the contraluminal dicarboxylate transport. Luminally, fluorescein and SF interacted with the lactate transporter (apparent Ki, approximately 3.0 mmol/L), whereas SF and fluorescein-5(6)-sulfonate had a very weak inhibitory potency against luminal sulfate transport (apparent Ki, 30 to 40 mmol/L). Because of its relatively low interference with the contraluminal sulfate transport, we preferred SF in the following study (protein binding, 88%) over fluorescein-5(6)-sulfonate (protein binding, 43.3%) and fluorescein (protein binding, 77.3%). A bolus injection of SF was given together with [14C]inulin into the jugular vein to rats in mannitol diuresis. Excretion of both substances in the urine was measured in 5-min samples. Fluorescence of the kidney surface was monitored at the exposed kidney with a photocell (excitation light, 470 nm; emission light, 530 nm). The effect of interfering substances was evaluated by their application 1 min before, simultaneously, or 1 min after SF bolus injection. PAH < probenecid < apalcillin inhibited SF excretion in the urine and, to a similar degree, SF fluorescence in cortical tissue. Inhibition was strongest when the substances were given simultaneously with SF. With the injection of alpha-ketoglutarate, glutarate, and succinate, an increase of SF excretion in the urine and, partially also, of SF content in tissue was seen. Tetrafluorosuccinate and mercaptosuccinate inhibited urinary SF excretion and tissue fluorescence strongly. Therefore, SF secretion is completely inhibited whereas filtration remained unaffected. The injection of acetate, lactate, and pyruvate as well as of 2-chloropropionate and thiosulfate did not change urinary excretion and tissue fluorescence of SF significantly. In SF-preloaded animals, the injection of probenecid, apalcillin, tetrafluorosuccinate, and mercaptosuccinate caused an immediate decrease of cellular SF content, whereas the injection of glutarate caused an increase. SF fluorescence in tissue was linearly related to urinary excretion of SF, whereas urinary excretion of inulin was barely affected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8490120 TI - Serum albumin in patients on continuous ambulatory peritoneal dialysis- predictors and correlations with outcomes. AB - Serum albumin (SA) is a powerful predictor of patient morbidity and mortality in hemodialysis, but data are limited for continuous ambulatory peritoneal dialysis (CAPD). SA was monitored in 76 new CAPD patients over 222 6-month periods and mean SA was correlated with morbidity and mortality during those periods. The influence of initial SA on duration of technique survival was also investigated. To determine which factors best predict SA, correlations with patient demographics and with 6-month measurements of dialytic dose, protein intake, and peritoneal transport were sought. Mean SA overall was 34.1 +/- 3.3 g/L, and mean initial SA was 33.4 +/- 3.1 g/L. Mean SA was lower in diabetics and in those aged 65 or over. Mean SA tended to increase during the first year on CAPD, and this increase was maintained, except in patients aged 65 or over, where it tended to revert to initial values. SA correlated with hospital days (r = -0.20; P < 0.005), fatigue index (r = -0.20; P < 0.005), nerve conduction (P < 0.001), and a variety of laboratory values, and lower SA was associated with technique failure (P < 0.03) and death (P < 0.07). Initial, as well as ongoing, SA was predictive of technique failure (P < 0.05) and Cox proportional hazards regression showed that this predictive power was independent of age, sex, diabetes, and other factors (P = 0.05). The strongest predictors of low SA by stepwise multiple regression were diabetes, a higher dialysate-to-plasma creatinine equilibration ratio, older age, lower body weight, and shorter time on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490121 TI - Protein catabolic rate in patients with acute renal failure on continuous arteriovenous hemofiltration and total parenteral nutrition. AB - Continuous arteriovenous hemofiltration (CAVH) has been used to provide nutrition support to critically ill patients in acute renal failure (ARF). Limited information exists regarding protein needs of these patients. Nineteen postoperative patients in ARF and on CAVH and total parenteral nutrition (TPN) were studied (10 men; 9 women; mean age, 65 yr) to determine protein needs (protein catabolic rate; PCR), urea nitrogen appearance (UNA), and total nitrogen appearance (TNA). TPN was adjusted to meet the needs estimated by the Harris Benedict and Long equations. A total of 38 24-h studies were conducted on the 19 subjects. TNA, UNA, and PCR were determined by direct measurement of body losses and calculation of body pool nitrogen changes. Patients received an average of 93.9 +/- 30.5 g of protein (1.4 g/kg) and 2,600 +/- 534 kcal/day in TPN. Mean PCR was 117.5 +/- 42.8 g/day; UNA was 18.3 +/- 6.9 g/day. TNA and UNA were strongly correlated (r = 0.99; P < 0.001). PCR was less strongly correlated with estimated protein needs (r = 0.35; P = 0.03). A regression equation was developed describing the relationship between TNA and UNA as follows: TNA = 1.895 + 0.9444 (UNA) or UNA = 0.1602 (PCR) - 0.916. On the basis of this study, CAVH permits the provision of adequate nutrition support to critically ill, unstable patients. It appears that the protein needs of patients in ARF on CAVH can be accurately estimated by determining UNA through the measurement of urea losses and urea body pool changes and by regression equations to calculate PCR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490122 TI - Angiotensin or thromboxane receptor antagonism in rats with congenital hydronephrosis. AB - A technique for the measurement of GFR without collection of urine in rats was experimentally validated and applied to experiments designed to: (1) evaluate the degree of reduction of GFR in rats with congenital, unilateral hydronephrosis; and (2) to determine if the reduction in renal function is mediated by angiotensin II and/or thromboxane A2 mechanisms. Simultaneous measurements of GFR by a constant-infusion technique and the traditional inulin clearance technique in rats with either one or two normal kidneys were highly correlated (r = 0.934; P < 0.001; N = 17). GFR was approximately 24% lower (P < 0.001) in rats with congenital unilateral hydronephrosis than in rats with a normal kidney. The GFR in rats with hydronephrosis infused with a receptor blocker for either angiotensin II or thromboxane A2 was greater than the GFR in hydronephrotic kidneys without blockade and was not significantly different (P > 0.05) from that in rats with normal kidneys. These results indicate that a constant inulin infusion technique without urine collections can be used to accurately measure GFR in congenitally hydronephrotic kidneys, rendering values free from possible residual pelvic volume artifact. In addition, these results also indicate that a significant 24% reduction in GFR occurs in congenital unilateral hydronephrosis and is mediated by angiotensin II and thromboxane A2 mechanisms. PMID- 8490123 TI - Prospects for reverse genetics in plants using recombination. PMID- 8490124 TI - Levels and location of expression of the Agrobacterium tumefaciens pTiA6 ipt gene promoter in transgenic tobacco. AB - The location of gene expression of the Agrobacterium tumefaciens ipt gene promoter in transgenic tobacco plants was examined using the beta-glucuronidase (GUS) reporter gene. Expression of GUS was detected in every organ and most cell types examined. The highest levels of GUS activity were found in roots. To further examine the transcriptional basis of this broad expression pattern, deletions in the 5' non-coding region of the gene were translationally fused to two promoterless reporter genes, encoding the enzymes chloramphenicol acetyl transferase (CAT) and beta-glucuronidase (GUS). Reporter enzyme assays revealed the existence of an upstream segment required for maximal promoter function, the 5' end of which is between -442 and -408 of the Pipt ATG codon. This upstream segment is required for maximal levels of GUS expression in roots, but not in other organs, and a tobacco suspension-cultured cell line. The implications of broad ipt expression on the process of crown gall tumorigenesis are discussed. PMID- 8490125 TI - Sequence analysis of pre-ferredoxin-NADP(+)-reductase cDNA from Cyanophora paradoxa specifying a precursor for a nucleus-encoded cyanelle polypeptide. AB - A cDNA clone for pre-ferredoxin-NADP+ reductase (FNR) was obtained by screening a Cyanophora paradoxa expression library with antibodies specific for cyanelle FNR. The 1.4 kb transcript was derived from a single-copy gene. The precursor (41 kDa) and mature forms (34 kDa) of FNR were identified by western blotting of in vitro translation products and cyanelle extracts, respectively. The derived amino acid sequence of the mature form was corroborated by data from N-terminal protein sequencing and yielded identity scores from 58% to 62% upon comparison with cyanobacterial FNRs. Sequence conservation seemed to be even more pronounced in comparison with enzymes from higher plants, but using the neighbor joining method the C. paradoxa sequence was clearly positioned between the prokaryotic and eukaryotic sequences. The transit peptide of 65 or 66 amino acids appeared to be totally unrelated to those from spinach, pea and ice plant but showed overall characteristics of stroma-targeting peptides. PMID- 8490126 TI - cDNA cloning of ECP40, an embryogenic-cell protein in carrot, and its expression during somatic and zygotic embryogenesis. AB - A cDNA of 1.2 kb was isolated from a cDNA library of embryogenic cells of carrot (Daucus carota L.) by use of nucleotide sequences that encode two internal amino acid sequences of ECP40 (an embryogenic-cell protein with a relative molecular mass of 40,000). A genomic Southern blot using the cDNA as probe suggested that there are at least two genes for ECP40 in the carrot genome. The cDNA encoded an open reading frame of 306 amino acids, and the deduced amino-acid sequence was found to share two motifs, namely SSSSSSEDDGXGGRRKKGXXXKIKEKLXGG and EKKXXXDKIKXKLPG, with rab16 protein from rice and dehydrins from barley and maize. The level of expression of these proteins has been reported to be high during late embryogenesis and to be induced by a plant hormone, ABA. Accumulation of ECP40-specific transcripts started 18 days after flowering and continued until maturation of seeds, but the levels decreased within 24 h after imbibition. ECP40 and its mRNAs were detected in the endosperm and zygotic embryos of mature seeds by immunohistochemistry and in situ hybridization. Exogenous application of 0.1 mM ABA to carrot seedlings did not induce expression of the gene for ECP40, while drought treatment induced the accumulation of low levels of the mRNAs. During somatic embryogenesis, the mRNAs were found at high levels in embryogenic cells and at low levels in somatic embryos at the torpedo stage. Immunohistochemical analysis and in situ hybridization showed that both ECP40 and its transcripts were preferentially localized in the peripheral cells of the clusters of embryogenic cells. In somatic embryos, application of ABA resulted in increases in levels of mRNAs for ECP40 up to the levels in embryogenic cells, but no such increases were observed in ABA-treated embryogenic cells. The pattern of expression of the gene for ECP40 during somatic embryogenesis was basically the same as that of ECP31, another ABA-regulable embryogenic-cell protein of carrot, the presence of which has been correlated with the embryogenic competence of cultured cells (T. Kiyosue, S. Satoh, H. Kamada and H. Harada, Plant Physiol 95 (1991) 1077-1083). The various results together imply that a group of ABA inducible genes is expressed in these embryogenic cells. PMID- 8490127 TI - Co-transcription pattern of an introgressed operon in the maize chloroplast genome comprising four ATP synthase subunit genes and the ribosomal rps2. AB - Several examples of the introduction of a gene from one gene complex into another (introgression) are found when chloroplast RP gene clusters are compared to those in Escherichia coli or cyanobacteria. Here we describe the transcript pattern of one such cluster from maize (Zea mays) that includes the genes for 4 subunits of the thylakoid ATP synthase (atpI, H, F, A) and the rps2 gene. Twelve transcript species covering the size range from 7,000 to 800 nt were identified in RNA isolated from dark-grown and greening maize seedlings, and several of them were characterized by reverse transcription analysis. A major species of 6,200 nt, with its 5' end at 181 nt upstream of the initiating ATG of rps2, contained the transcripts of all the 5 genes. Two further sets of transcripts having their 5' ends ca. 120 and 50 nt upstream of the initiation codons of the atpI and atpH genes were also identified. Thus, this plastid gene cluster in maize is functionally organized as an operon with additional regulatory features to allow for increased accumulation of mRNAs for the thylakoid components. PMID- 8490128 TI - PCR-dependent amplification and sequence characterization of partial cDNAs encoding myosin-like proteins in Anemia phyllitidis (L.) Sw. and Arabidopsis thaliana (L.) Heynh. AB - Partial cDNAs encoding for myosin-like proteins from Anemia phyllitidis and Arabidopsis thaliana have been isolated using PCR technology. The deduced amino acid sequences show an average similarity up to 62% with known myosin heavy chain genes. From northern blot analysis we were able to estimate that transcripts of ca. 6.1 kb size are expressed in A. phyllitidis. PMID- 8490129 TI - Molecular cloning and expression of a Eucalyptus gunnii cDNA clone encoding cinnamyl alcohol dehydrogenase. AB - Cinnamyl alcohol dehydrogenase (CAD) catalyses the reduction of hydroxycinnamyl aldehydes (sinapyl, paracoumaryl, coniferyl aldehydes) to the corresponding alcohols which are the direct monomeric precursors of lignins. Recently, we have purified from Eucalyptus gunnii two isoforms of CAD (CAD1 and CAD2), distinct in their biochemical and functional properties. In this paper, we report the cloning of a CAD cDNA (pEuCAD2) isolated by screening a lambda gt11 library generated from cell suspension culture of Eucalyptus gunnii, using a tobacco CAD cDNA as a probe. This full-length clone (1392 bp) encodes a protein of 356 amino acids which corresponds to the subunit molecular weight of the CAD2 isoform. Sequence analysis revealed that CAD2 is very well conserved among species (78% homology with CAD from tobacco, a herbaceous angiosperm, and 81% with the partial sequence from a gymnosperm, loblolly pine). The identity of this clone was unambiguously demonstrated (1) by comparison with peptide sequence data from purified CAD2 and (2) by functional expression of the recombinant enzyme in Escherichia coli. Recombinant CAD showed the same properties as the natural isoform CAD2, in terms of electrophoretic mobility, polypeptide structure, substrate specificity and antigenicity. The CAD2 transcript is equally abundant in stems and leaves and at the limit of detection in roots. At the tissue level the CAD2 gene is highly expressed in xylem and virtually undetectable in phloem. PMID- 8490130 TI - A pathogen-induced gene of barley encodes a HSP90 homologue showing striking similarity to vertebrate forms resident in the endoplasmic reticulum. AB - The full-length nucleotide sequence of a barley (Hordeum vulgare L.) leaf mRNA, found to increase rapidly in amount during infection attempts by the powdery mildew fungus (Erysiphe graminis DC. ex Merat), is reported. The mRNA encodes a polypeptide of 809 amino acid residues which, by sequence comparison, was identified as a member of the 90 kDa heat shock protein (HSP90) family. The encoded protein most resembles the endoplasmic reticulum (ER) resident HSP90 protein, the 94 kDa glucose-regulated protein (GRP94) of vertebrates, as it possesses both the characteristic N-terminal domain including a signal peptide sequence and the C-terminal ER retention signal (Lys-Asp-Glu-Leu). A transcript cross-hybridizing at high stringency accumulated rapidly in leaves upon heat shock treatment. Genomic DNA blot analysis indicated the presence of a family of related genes in the barley genome. PMID- 8490131 TI - Enigmatic double-stranded RNA in Japonica rice. AB - We have found a linear, 16 kb, double-stranded RNA (dsRNA) in symptomless Japonica rice (Oryza sativa L.) that is not found in Indica rice (Oryza sativa L.). The dsRNA was detected in every tissue and at every developmental stage, and its copy number was approximately constant (about 20 copies/cell). Double stranded RNA was also detected in two strains of Oryza rufipogon (an ancestor of O. sativa). Hybridization experiments indicated that the dsRNA of O. rufipogon was homologous but not identical to that of O. sativa. The sequence of about 13.2 kb of the dsRNA was determined and two open reading frames (ORFs) were found. The larger ORF (ORF B) was more than 12,351 nucleotides long and encoded more than 4,117 amino acid residues. PMID- 8490132 TI - The reconstruction and expression of a Bacillus thuringiensis cryIIIA gene in protoplasts and potato plants. AB - A Bacillus thuringiensis (B.t.) cryIIIA delta-endotoxin gene was designed for optimal expression in plants. The modified cry gene has the codon usage pattern of an average dicot gene and does not contain AT-rich nucleotide sequences typical of native B.t. cry genes. We assembled the 1.8 kb cryIIIA gene in nine blocks of three oligonucleotide pairs. For two DNA blocks, the polymerase chain reaction was used to enrich for correctly ligated pairs. We compared modified cryIIIA gene with native gene expression by electroporation of dicot (carrot) and monocot (corn) protoplasts. CryIIIA-specific RNA and protein was detected in carrot and corn protoplasts only after electroporation with the rebuilt gene. Transgenic potato lines were generated containing the redesigned cryIIIA gene under the transcriptional control of a chimeric CaMV 35S/mannopine synthetase (Mac) promoter. Out of 63 transgenic potato lines, 58 controlled first-instar Colorado potato beetle (CPB) larvae in bioassays. Egg masses which produced ca. 250,000 CPB larvae were placed on replicate clones of 56 transgenic potatoes. No CPB larvae developed past the second instar on any of these plants. Plants expressing high levels of delta-endotoxin were identified by their toxicity to more resistant third-instar larvae. We show there was good correlation between insect control and the levels of delta-endotoxin RNA and protein. PMID- 8490133 TI - Identification of protein-binding DNA sequences in an auxin-regulated gene of soybean. AB - The promoter region of a soybean auxin-responsive gene, GmAux28, was analyzed to identify protein-binding DNA sequences that may be involved in regulation of expression. Using DNase I footprinting and gel mobility shift assays, multiple regions of interaction, including eight major protein-binding sites, were observed in the GmAux28 gene. Two sequence motifs, TGACGACA and TCCACGTGTC, related to as-1/Hex and G-box elements, respectively, found in several plant promoters, were identified. Four distinct A/T-rich domains were identified; such A/T-rich domains appear to modulate, but not to specify, the expression of many genes. Two new sequence motifs, delta-1 (D1) and delta-4 (D4) were also identified. D1 and D4 share a very similar core sequence, TAGTxxCTGT and TAGTxCTGT, respectively. In gel mobility shift analyses, D1 and D4 elements exhibit a complex interaction of binding proteins. The GmAux22 promoter also contains D1-related elements which compete with the GmAux28 elements. Sequence comparisons have identified D1/D4-like sequences in several other auxin responsive genes suggesting the possible importance of D1/D4 and the respective binding proteins in the regulation of expression of these genes. PMID- 8490134 TI - RNA editing gives a new meaning to the genetic information in mitochondria and chloroplasts. AB - RNA editing in plant mitochondria and chloroplasts alters mRNA sequences to code for different proteins than the DNA. Most of these C-to-U transitions occur in open reading frames, but a few are observed in intron sequences. Influences of the nuclear genome on editing patterns suggest that cytoplasmic factors participate in this process. PMID- 8490135 TI - Structure and expression of the S locus-related genes of maize. AB - The extracellular of the putative receptor-like protein kinase, ZmPK1, is related to the self-incompatibility locus (S-locus) genes of Brassica. We have isolated and characterized a genomic DNA clone of ZmPK1 and three additional genes from maize that are highly related to ZmPK1. These three S-locus related genes do not appear to have the protein kinase catalytic domain that is found in ZmPK1. One or more of these genes are expressed specifically in the silks. This initial description of S-locus related genes in monocotyledonous plants suggests that the S-locus domain may be involved in several different cellular functions in a wide variety of plants. PMID- 8490136 TI - Kinetic induction of oat shoot pulvinus invertase mRNA by gravistimulation and partial cDNA cloning by the polymerase chain reaction. AB - An asymmetric (top vs. bottom halves of pulvini) induction of invertase mRNA by gravistimulation was analyzed in oat shoot pulvini. Total RNA and poly(A)+ RNA, isolated from oat pulvini, and two oligonucleotide primers, corresponding to two conserved amino acid sequences (NDPNG and WECPD) found in invertase from other species, were used for the polymerase chain reaction (PCR). A partial length cDNA (550 bp) was obtained and characterized. A 62% nucleotide sequence homology and 58% deduced amino acid sequence homology, as compared to beta-fructosidase of carrot cell wall, was found. Northern blot analysis showed that there was an obviously transient induction of invertase mRNA by gravistimulation in the oat pulvinus system. The mRNA was rapidly induced to a maximum level at 1 h after gravistimulation treatment and gradually decreased afterwards. The mRNA level in the bottom half of the oat pulvinus was significantly higher than that in the top half of the pulvinus tissue. The kinetic induction of invertase mRNA was consistent with the transient accumulation of invertase activity during the graviresponse of the pulvinus. This indicates that the expression of the invertase gene(s) could be regulated by gravistimulation at the transcriptional level. Southern blot analysis showed that there were two to three genomic DNA fragments which hybridized with the partial-length invertase cDNA. PMID- 8490137 TI - Stabilisation of a yeast artificial chromosome containing plant DNA using a recombination-deficient host. AB - The large genomes of many plant species contain numerous dispersed repeat sequences. The problem of large-scale structural instability due to the presence of such repeats in yeast artificial chromosome (YAC) clones was assessed. The feasibility of stabilising plant sequences prone to rearrangement in YACs was demonstrated using a host yeast strain deficient in recombination. PMID- 8490138 TI - In vivo suppression of phytochrome aggregation by the GroE chaperonins in Escherichia coli. AB - When expressed in Escherichia coli, a truncated form of phytochrome (oat PHYA AP3 residues 464-1129) self associates to form a series of products ranging in size from monomers to aggregates of greater than 20 subunits. When these same phytochrome sequences are coexpressed with the chaperonins GroEL and GroES, the truncated phytochrome migrates as a native-like dimer in size exclusion chromatography and no higher-order aggregates were detected. GroEL and GroES inhibition of phytochrome aggregation in E. coli presumably occurs via the suppression of folding pathways leading to incorrectly folded phytochrome. PMID- 8490139 TI - Sequence of a novel plant ras-related cDNA from Pisum sativum. AB - A clone isolated from a purple podded pea (Pisum sativum L.) cDNA library was shown to contain the complete coding sequence of a polypeptide with considerable homology to various members of the ras superfamily. The ras superfamily are a group of monomeric GTP-binding proteins of 21-25 kDa found in eukaryotic cells. Conserved sequences in the isolated clone include the GTP-binding site, GDP/GTP hydrolysis domain and C-terminal Cys residues involved in membrane attachment. Comparisons of the predicted amino acid sequence with those of other ras proteins show significantly higher homologies (ca. 70%) to two mammalian gene products, those of the BRL-ras oncogene, and the canine rab7 gene, than to any of the plant ras gene products so far identified (< 40% homology). The high percentage of amino acid identity suggests that this cDNA may be the product of a gene, designated Psa-rab, which is the plant counterpart of rab7. Rab/ypt proteins are a subfamily of the ras superfamily thought to be involved in intracellular transport from the endoplasmic reticulum to the Golgi apparatus and in vesicular transport. Northern blot hybridisation analysis of total RNA from green and purple podded pea revealed a mRNA species of approximately the same size as the isolated cDNAs. PMID- 8490140 TI - Nitrite reductase gene from Synechococcus sp. PCC 7942: homology between cyanobacterial and higher-plant nitrite reductases. AB - The gene encoding nitrite reductase (nir) from the cyanobacterium Synechococcus sp. PCC 7942 has been identified and sequenced. This gene comprises 1536 nucleotides and would encode a polypeptide of 56,506 Da that shows similarity to nitrite reductase from higher plants and to the sulfite reductase hemoprotein from enteric bacteria. Identities found at positions corresponding to those amino acids which in the above-mentioned proteins hold the Fe4S4-siroheme active center suggest that nitrite reductase from Synechococcus bears an active site much alike that present in those reductases. The fact that the Synechococcus and higher plant nitrite reductases are homologous proteins gives support to the endosymbiont theory for the origin of chloroplasts. PMID- 8490141 TI - Identification and characterization of a second plasma membrane H(+)-ATPase gene subfamily in Nicotiana plumbaginifolia. AB - A cDNA clone was isolated for a fourth pma gene encoding a putative plasma membrane H(+)-ATPase of Nicotiana plumbaginifolia. The sequence of the predicted 952 residue PMA4 polypeptide was compared with those of other known plant PMAs, revealing a higher identity with the Arabidopsis thaliana proteins (86-89%) than with the other three N. plumbaginifolia PMA proteins (80-82%). This supports the view that there are two pma subfamilies which probably arose from a gene duplication predating the separation of the Dilleniidae and Asteridae plant subclasses. Measured pma4 transcript levels indicate that pma4 is similarly expressed in root, stem, leaf, and flower tissues, contrary to the pmal-3 subfamily whose members displayed differential expression according to the organ. PMID- 8490142 TI - Proteins encoded by an auxin-regulated gene family of tobacco share limited but significant homology with glutathione S-transferases and one member indeed shows in vitro GST activity. AB - A number of cDNAs corresponding to auxin-regulated mRNAs have been isolated from tobacco and found to be encoded by a multigene family consisting of three subfamilies. Homologous proteins have been isolated independently from soybean and potato. Here we report that the encoded proteins show a limited but significant homology to both plant and animal glutathione S-transferases (GST, EC 2.5.1.18). For the protein NT103, encoded by a member of the Nt103 subfamily, we demonstrate an in vitro GST activity. This is the first time a function is attributed to a member of this group of auxin-induced proteins or any of its homologues. The implications of this finding and the possible relationships between auxins and GSTs are discussed. PMID- 8490143 TI - cis-acting regulatory regions of the soybean seed storage 11S globulin gene and their interactions with seed embryo factors. AB - A 2.2 kb fragment containing the 5'-flanking region of the soybean glycinin A2B1a gene and its successive deletions with a shorter 5'-flanking sequence were fused, in frame, to the beta-glucuronidase (GUS) reporter gene. The resultant fusions were introduced into tobacco plants via Agrobacterium tumefaciens. Assays of the GUS activity in seeds of transgenic tobacco showed that the upstream region, -657 to -327 (relative to the transcription initiation site [+1]), of the glycinin gene is required for optimal expression of the transformed gene. Interactions between embryo nuclear factors and DNA fragments covering the downstream region of -326, in which are included the TATA box and legumin boxes, were not apparent. The embryo factors capable of binding specifically to three subregions, -653 to 527, -526 to -422, and -427 to -321, of the upstream regulatory region were detected. Such factors appeared to be organ-specific and could be found solely in developing seeds at the early middle stage of embryogenesis (around 24 days after flowering). Evidence obtained by characterizing the nature of the binding proteins and by gel mobility shift assays established that the same factor does interact with a consensus motif 5'-ATA/TATTTCN-/CTA-3' which occurs four times in the cis-acting regulatory region between -657 and -327. Moreover, this conserved motif could also be found in the 5' regulatory region of another glycinin A1aB1b gene. Thus it is likely that the observed interaction between the nuclear factor and the conserved motifs would lead to activation of transcription from the glycinin genes in maturing soybean seeds. PMID- 8490145 TI - [Outpatient peripheral angioplasty--safety and limits]. PMID- 8490144 TI - Tobacco proteinase inhibitor I genes are locally, but not systemically induced by stress. AB - A cDNA library of tobacco mosaic virus (TMV)-infected tobacco was screened with polymerase chain reaction products obtained using a degenerate primer corresponding to proteinase inhibitor I (PI-I) of tomato and potato. The resulting clones encoded two highly similar, putative tobacco PI-I proteins, indicating that both genes identified in tobacco are probably expressed. The tobacco PI-I's were approximately 50% identical to wound-inducible potato and tomato PI-I and 80% identical to an ethylene-regulated tomato PI-I. Northern blot analyses indicated that healthy tobacco leaf contains only minor amounts of PI-I mRNA, and that the inhibitor genes are induced by TMV infection, salicylate treatment, ethephon spraying, UV light irradiation and wounding. The results indicate that the tobacco PI-I genes are coordinately expressed with the genes for the basic pathogenesis-related proteins. Contrary to PI-I genes of tomato and potato, wound induction of the tobacco genes occurs only locally; the upper, unwounded leaves do not show any wound-induced PI-I gene expression. PMID- 8490146 TI - [Spiral CT in aortic aneurysms. 2D and 3D reconstructions and CT angiography]. AB - Spiral CT was performed in 8 normals and 40 patients with alterations of the large thoracic and abdominal vessels. It proved to be the ideal basis for 2D and 3D reconstructions. In 2D reconstruction the topographic aspects of aortic aneurysms were displayed better compared to the axial scans. In 3D reconstruction the segmentation of small vessels, and vessels running parallel to the scan plane showed problems. Stenoses were displayed unsatisfactory. In patients with aortic aneurysms 3D reconstruction showed well the location and dimension of the aneurysm as well as its position to branching arteries and the intraarterial thrombus. In case of dissecting aneurysms the true and the false lumen could clearly be distinguished. Colour-coded 3D reconstruction proved to be valuable to illustrate topographic information that could be detected only with difficulty on examining the original axial scan. PMID- 8490147 TI - [A comparison of color duplex sonography with selective penile DSA in assessing erectile dysfunction]. AB - 42 patients with suspected vasculogenic impotence were examined via colour duplex sonography. Penile vascular anatomy was mapped and peak velocity was determined in both cavernous arteries before and after intracorporeal injection of 15 mg papaverine and 0.5 mg regitine. In all patients the results could be compared with selective penile pharmacoangiography as the gold standard. In 34/42 patients colour Duplex sonography and angiography led to an identical evaluation of penile blood supply. 4 patients were classified false-negative and 4 patients false positive. Sensitivity and specificity were calculated for each side separately. Sensitivity was 82.4% for left side angiogram and 83.3% for right side angiogram. Specificity was 88% for left side angiogram and 87.5% for right side angiogram. Peak flow velocity was significantly diminished in pathological angiograms. PMID- 8490148 TI - [CT arterioportography in the spiral technic for the demonstration of liver metastases]. AB - CT arterioportography using indirect portal venous application of contrast media is the most sensitive preoperative diagnostic technique for detection of liver metastases. Spiral CT allows continuous examination of the liver (no gap) during a single breathhold. Due to short measurement times an optimized vessel and tissue contrast can be achieved during the portal venous phase. Compared with intraoperative ultrasonography CTAP using spiral CT offers similar sensitivity (96%) in the detection of liver metastases and thus emerges as an important technique for diagnosis and follow-up of liver metastases. PMID- 8490149 TI - [The MRT criteria for the differentiation of "pseudotumorous" lesions from bone sarcomas of the extremities]. AB - The MRT scans of 57 patients with Ewing or osteosarcomas and 34 patients with haematogenous osteomyelitis or periostitis/stress fractures were examined in order to determine whether a distinction between benign or malignant lesions is possible. Four criteria were evaluated: the margin of the bone marrow component; intensity and homogeneity of the T1 weighted signal in the bone marrow; presence of an extraosseous structured soft tissue mass and/or soft tissue edema. It was found that central osteosarcomas and Ewing's sarcomas reduced signal intensity of the marrow to become muscle-isointense with a well-defined margin. In acute haematogenous osteomyelitis and periostitis/stress fracture the marrow lesion was not sharply demarcated. In contrast to patients with bone sarcomas, only one case of osteomyelitis showed an extraosseous structured soft tissue mass. On the basis of these findings we believe that acute haematogenous osteomyelitis can be distinguished with high degree of accuracy from Ewing's sarcoma and central osteosarcomas. PMID- 8490150 TI - [The MRT of the breast with 2D-spin-echo and gradient-echo sequences in diagnostically problematic cases]. AB - One or both breasts of 296 patients with equivocal clinical or mammographic findings were examined with MRI. T1-weighted spin-echo (SE) and gradient-echo (FFE) sequences were acquired before and after i.v. application of Gadolinium DTPA. 50 lesions with enhancement after Gd-DTPA were biopsied--26 carcinomas, 17 proliferating mastopathic tissues, 5 fibroadenomas and 1 abscess were found. Contrast enhanced MRI with 2D-SE and FFE sequences is an effective technique for evaluating suspicious breast lesions with high diagnostic accuracy. PMID- 8490151 TI - [The value of computed tomography in the diagnosis of the local and lymph node recurrences of head and neck tumors]. AB - 544 CT studies of 231 patients were evaluated retrospectively to assess the role of CT in posttherapeutic monitoring of patients with head and neck tumours. CT (80%) was inferior to clinical evaluation (87%) in diagnosing recurrent malignancy due to a lack of specificity (76 vs. 92%). With CT small recurrencies were missed. Occasionally evaluation of the oral cavity was impaired by metal artifacts (dental fillings). However with larger recurrent tumours, CT offered important additional information regarding extent, infiltration of deeper compartments and bony destruction in 51% of the cases. CT (95%) was superior to clinical evaluation (80%) in diagnosing recurrent lymph node metastases. A baseline CT study at about 6-8 weeks after the end of therapy is of great importance for follow-up studies. PMID- 8490152 TI - [The value of magnetic resonance tomography and computed tomography in the tumor staging of laryngeal and hypopharyngeal carcinomas]. AB - 43 patients with malignant tumours of the larynx or hypopharynx were examined by MRT and CT to compare their accuracy for T-staging. There was histological confirmation in all cases. Histological studies showed an accuracy in T-staging of 90% for MRT and 82% for CT. Differentiation between stages T2/T3 and T3/T4 is possible in most cases by either method. A source of error is the difficulty of differentiating oedema or inflammatory changes from tumour. This led to occasional overinterpretation of the T4 stage. Demonstration of cartilage involvement was easier with MRT (88%) than with CT (84%). The use of Gd-DTPA with T1 weighted and proton weighted sequences allows earlier diagnosis of cartilage invasion. Early cartilage involvement may be missed by CT when it is seen on MRT. In addition, the ability to produce coronal and sagittal images by MRT makes this superior to CT in judging tumour extension. PMID- 8490153 TI - [Magnetic resonance tomography with fast spin-echo sequences--the results in the ENT area]. AB - The use of T2-weighted spin-echo sequences is mandatory for identifying tumours in the ENT region and for differential diagnosis of pathological findings. A highly promising alternative to time-consuming conventional SE sequences is now available in the fast-spin-echo sequences (FSE). FSE was compared with the conventional SE (CSE) basing on 100 assessments of examinations of 20 patients. RESULTS: Conventional SE = TR/TE = 1800/90 ms with one average (NEX), FSE = TR/TE = 3200/120 ms with 4 averages (NEX). Measurement time CSE 6:59 min, FSE 3:12 min. Analysis was performed in analogy to on ROC analysis by 5 radiologists as a blind study. The anatomic differentiation and contrast performance were compared as well as the differentiation and definition of lesion and lymphatic node and a subjective overall assessment. Differentiation of pathological findings was the same with both sequences. FSE was superior to CSE in the visualisation of normal tissue, lymph nodes and also in the subjective overall assessment. The following criteria were employed in the subjective overall valuation: sum total of impressions gathered from contrast behaviour or performance, susceptibility to artifacts, and signal-to-noise ratio. Due to the definitely improved parameters of image quality and the markedly reduced scanning time--which is reduced to 50%- FSE will replace the conventional spin-echo sequence in routine diagnostics. PMID- 8490154 TI - [The initial clinical experiences with a dynamic FLASH-2D sequence in tumors of the head and neck area]. AB - 28 patients with clinically confirmed head and neck tumours were examined by MRI. The results of a dynamic FLASH-2D sequence and a Gd-DTPA enhanced T1-weighted sequence were analysed and retrospectively compared with surgery and pathological findings. The extent of tumours was clearly defined by the dynamic technique in 21 cases. Furthermore, it was found to be superior for the purpose of demonstrating contrast behaviour and concerning T-classification. Here the dynamic FLASH-2D sequence proved to be an important supplement for preoperative diagnosis. PMID- 8490155 TI - [Liver regeneration in man. A prospective CT-volumetric study]. AB - To get reliable data on human liver regeneration we performed CT volumetry in 25 patients who underwent partial hepatectomy for benign and malignant liver tumours preoperatively and at least one year postoperatively in regular intervals in a prospective study. All patients received standardised CT-scans preoperatively and two weeks, 3, 6 and 12 months post-operatively. The resected specimen size was determined by water displacement. We were able to demonstrate human liver regeneration. Contrary to the well-known animal model the amount of regeneration in humans is less and regeneration takes a longer time. We did not find any statistical correlation to extent of resection, age of patients and other parameters. On the contrary, the human liver seems to regenerate until a certain relationship of liver volume and body-surface area is reached: 0.8 l/m2. PMID- 8490156 TI - [Measurement data of the lateral lumbosacral region in healthy subjects during the growth period]. AB - The following measurement data were obtained to characterise the healthy lumbosacral profile, via lateral x-rays taken of 90 female and 90 male patients between 8 and 17 years of age: Degree of slip 0%, slip angle -21.3 degrees, sacral inclination 45.5 degrees, posterior lumbosacral angle 140.5 degrees. These measurement data are independent of age and sex. If an adolescent suffers from lumbosacral spondylolisthesis, they will quantify the process of slip that has taken place, more accurately than the conventional method after Meyerding. If the shape of the sacral vertebra is considered at the same time, these parameters will also enable to assess the risk of progression of spondylolisthesis to a degree that is satisfactorily accurate in clinical practice. PMID- 8490157 TI - [The initial results of lumbar dual-energy x-ray absorptiometry (DEXA) compared to double-energy quantitative computed tomography (DE-QCT)]. AB - Bone density measurements were performed on 51 patients with suspected osteoporosis. We used DE-QCT and DEXA. The methods were compared with regard to deviation from normal. In 29 of the 51 patients there was more than half standard deviation and in 12 of the 51 cases there was more than a full standard deviation. PMID- 8490158 TI - [Osteoporosis diagnosis by broad-band ultrasound attenuation (BUA): its correlation with established measurement procedures of bone densitometry]. AB - Broadband ultrasound attenuation (BUA) measurements of the os calcis of 54 women were correlated to single-energy x-ray absorptiometry (SXA) of the os calcis, dual-energy x-ray absorptiometry (DXA) of the lumbar spine, age and weight. The reproducibility of the BUA measurements was 2.1%. BUA was significantly correlated with SXA (r = 0.7), DXA (r = 0.5) and age (r = 0.6). BUA values ranged from 42 to 117 dB/MHz. Our results confirm BUA's potential as a simple, inexpensive, radiation free, and precise alternative technique for osteoporosis diagnostics of the os calcis. However, the correlation observed with bone mineral density of the spine is too weak to use BUA for predicting the lumbar density status. The ability of BUA to predict the risk of osteoporotic fractures has to be determined directly by assessing the association of BUA and the prevalence or preferably the incidence of fractures. PMID- 8490159 TI - [The determination of the surface and organ doses in the AMBER system. Advanced Multiple Beam Equalization Radiography]. AB - Surface and organ doses were determined by means of thermoluminescence dosimetry with the Alderson-Rando phantom and the patient, for the AMBER thoracic imaging system, sensitivity class 400, and the conventional grid screen stand, sensitivity class 200. The dose on entering the body, which varied according to object-dependent modulation of x-ray intensity, was 140 microGy for the mediastinum and 96 microGy for the lung in p.a. AMBER takes, and hence was comparable with the entrance dose of 132 microGy with the conventional grid screen stand. In lateral takes the entrance doses were lower with the AMBER system (302 microGy) than with conventional takes (593 microGy). Exposure of the gonads at the AMBER system for p.a. thoracic takes was lower than at the screen grid stand in females (4-6 microGy). More unfavourable values were measured for the gonad exposure in males (2-0.8 micrograms). PMID- 8490160 TI - [Percutaneous sonographic gastrostomy]. PMID- 8490161 TI - [An atraumatic Sprotte needle for double-contrast CT arthrography of the shoulder joint]. PMID- 8490162 TI - [A giant, predominantly cystic local recurrence of prostatic carcinoma. Its imaging in sonography and computed tomography]. PMID- 8490163 TI - Autoantibodies in chronic lymphocytic leukemia and related systemic autoimmune diseases. PMID- 8490164 TI - Expression of the ABL-BCR fusion gene in Philadelphia-positive acute lymphoblastic leukemia. AB - We have previously shown that the chimeric gene ABL-BCR, formed on the derivative chromosome 9q+ as a result of the t(9;22) translocation, is transcriptionally active in 65% of chronic myeloid leukemia patients. We have now used the same technique, reverse transcription/polymerase chain reaction amplification of ABL BCR transcripts, to study nine patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL); seven expressed the P190 and two the P210 type of BCR-ABL fusion protein. All seven patients with P190 had ABL-BCR transcripts containing a junction between ABL exon Ib and BCR exon 2 (Ib-e2); in two cases, ABL-BCR transcripts with the Ia-e2 junction type were also present. Of the two P210 ALL patients, one had a Ib-b4 ABL-BCR transcript and the other showed no detectable ABL-BCR expression. Although the BCR-ABL gene is probably fundamental in the pathogenesis of the Ph+ leukemias, differential expression of the ABL-BCR gene could contribute to the biologic heterogeneity of the disease. PMID- 8490165 TI - Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event. AB - Migration of neutrophils through endothelial cells (EC) and induction of cytokine secretion are two well-documented events during the inflammatory reaction. The inflammatory, chemotactic cytokine interleukin-8 (IL-8) is secreted by EC in response to IL-1 stimulation. In this study, we show that platelets activated with either adenosine-5'-diphosphate or epinephrine induce IL-8 secretion by EC. This stimulatory activity was found to be associated with sedimented platelets after activation. Blockade of IL-1 receptors on EC with IL-1 receptor antagonist (IL-1Ra) decreased the stimulatory effect of whole activated platelet preparations by 59% (P < .05). Similarly, IL-1Ra pretreatment of EC reduced the stimulatory effect of sedimented activated platelets by 60% (P < .01). In addition, we treated human blood donors with 750 mg of oral aspirin, and evaluated the stimulatory effect of epinephrine-activated platelets on IL-8 secretion by EC. IL-8 synthesis after aspirin ingestion was inhibited by 90% (P < .01) as compared with the preaspirin stimulation. These observations show that activated platelets induce IL-8 secretion via membrane-associated IL-1 activity, and provide a novel relationship between coagulation and inflammation that could be relevant to several diseases. PMID- 8490166 TI - A randomized controlled phase III trial of recombinant human granulocyte colony stimulating factor (filgrastim) for treatment of severe chronic neutropenia. AB - Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection related events. PMID- 8490167 TI - Effect of tunicamycin treatment on ligand binding to the erythropoietin receptor: conversion from two classes of binding sites to a single class. AB - Scatchard analyses of erythropoietin (EPO) binding to its receptor (EPO-R) have shown that some erythroid cells display a biphasic nature of the ligand saturation curve, indicating the presence of two classes of binding sites with different affinities. The biochemical basis accounting for this observation is unknown. We found that the culture of a human erythroleukemia cell line with tunicamycin, an inhibitor of N-glycosylation, converted the biphasic Scatchard plot to a single phase with high-affinity sites. Scatchard plots of baby hamster kidney (BHK) cells that had been engineered to express cloned mouse EPO-R were also biphasic and the plots of cells cultured with tunicamycin became a single phase with high-affinity sites. Mouse EPO-R is glycosylated at one asparagine residue in the extracellular region. The mutant EPO-R, in which asparagine residue responsible for N-glycosylation was replaced with glutamine residue, was expressed on BHK cells. Unexpectedly, mutant EPO-R was similar in ligand binding to wild-type EPO-R. BHK cells that expressed mutant EPO-R showed biphasic Scatchard plots that were converted to single-phase plots with only high-affinity sites by tunicamycin treatment. These results indicate that the N-linked sugar of EPO-R is not involved in the manifestation of two classes of binding sites, and that there is a yet unidentified glycoprotein crucial for the ligand-saturation characteristics of EPO-R. PMID- 8490168 TI - Mechanism of differential inhibition of factor-dependent cell proliferation by transforming growth factor-beta 1: selective uncoupling of FMS from MYC. AB - Transforming growth factor-beta 1 (TGF-beta 1) selectively modulates hematopoietic cell proliferation. The proliferation of FDC-P1 clone MAC-11, a factor-dependent murine myeloid progenitor cell line, was inhibited differentially by TGF-beta 1: strongly in macrophage colony-stimulating factor (M CSF), mildly in interleukin-3, and not at all in granulocyte-macrophage-CSF (GM CSF). Flow cytometry and Western blots showed an unexpected increase in expression of FMS, the receptor for M-CSF, in response to TGF-beta 1. Metabolic labeling with 35S-methionine showed that synthesis of FMS protein accelerated in response to TGF-beta 1, whereas its degradation was unaffected. Northern analyses showed a rapid increase in c-fms RNA after the addition of TGF-beta 1. TGF-beta 1 did not affect kinase activity, cellular phosphotyrosine response, or internalization of FMS. However, TGF-beta 1 inhibited the induction by M-CSF of c myc RNA analyzed on Northern blots and protein detected by radioimmuno precipitation. TGF-beta 1 did not affect induction of c-myc expression by GM-CSF or induction of c-fos or c-jun by M-CSF. Therefore, FMS and the GM-CSF receptor induce c-myc via signal transduction pathways that differ in that only the former is inhibited by TGF-beta 1. This inhibition may account for the selective growth regulation by TGF-beta 1. PMID- 8490169 TI - Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups. AB - Annexin V, a protein with a high affinity and a strict specificity for aminophospholipids at physiologic calcium concentrations, was used to probe platelet activation and the development of procoagulant activity. Platelet secretion was studied in parallel using VH10, a murine monoclonal antibody specific for GMP-140, an alpha-granule membrane glycoprotein. Both proteins were labeled with fluorescein isothiocyanate and platelet activation was assessed by flow cytometry. Microparticles, which are shed from the platelet surface and also support procoagulant activity, were distinguished from platelets according to their associated light scattering signal. The relative ability of different inducers to trigger exposure of the procoagulant surface and microparticle formation was: ionophore A23187 > thrombin plus collagen > collagen > thrombin. The density of aminophospholipid on microparticles was higher than on remnant platelets. Platelet activation by these agonists was accompanied by GMP-140 exposure, both on platelets and microparticles. Here, thrombin was the most efficient agonist. The mechanisms responsible for the above processes were investigated using E-64-d, a specific membrane-permeable inhibitor of Ca(2+) activated protease (calpain); tetracaine, an activator of calpain; and N ethylmaleimide and diamide, two sulfhydryl-reactive agents. These agents were added to platelets alone or before stimulation by agonists. Calpain activity was assessed by the hydrolysis of cytoskeletal proteins as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results showed that calpain activity is not essential for aminophospholipid translocation or for secretion. In contrast, although sulfhydryl-reactive agents alone can trigger procoagulant activity, they inhibit microvesicle formation and platelet secretion induced by the above agonists, suggesting that different mechanisms account for these phenomena. The use of annexin V in flow cytometry is a rapid method to assess procoagulant activity in platelets and the loss of phospholipid asymmetry in cell membranes. PMID- 8490170 TI - Binding of factor VIIa to tissue factor permits rapid antithrombin III/heparin inhibition of factor VIIa. AB - Because free factor VIIa is inactivated only very slowly by a plasma concentration of antithrombin III (AT III) even in the presence of heparin, it has been assumed that AT III plays no significant role in regulating the initiation of tissue factor-dependent blood coagulation. However, in the present study, we present evidence that factor VIIa bound to tissue factor, unlike free factor VIIa, is readily inactivated by AT III in the presence of heparin. In a reaction mixture containing calcium ions and approximately equimolar concentrations of relipidated tissue factor (8.9 nmol/L) and factor VIIa (10 nmol/L), AT III (100 micrograms/mL) plus heparin (1 U/mL) inhibited 50% of the factor VIIa coagulant activity of the reaction mixture within 5 minutes. AT III/heparin was also shown to inhibit the catalytic activity towards factor X of factor VIIa/tissue factor complexes formed on monolayers of an ovarian carcinoma cell line (OC-2008) that constitutively expresses surface membrane tissue factor. AT III, even in the absence of exogenously added heparin, substantially inhibited the functional activity of factor VIIa/cell surface tissue factor complexes on intact monolayers. AT III alone and AT III/heparin, to a greater extent, also inhibited factor VIIa on "nonfunctional" factor VIIa/tissue factor complexes on intact monolayers, with resultant inhibition of their expression of factor VIIa/tissue factor catalytic activity toward factor X after cell lysis. The potential physiologic significance of these findings is discussed. PMID- 8490171 TI - Inherited abnormalities in platelet organelles and platelet formation and associated altered expression of low molecular weight guanosine triphosphate binding proteins in the mouse pigment mutant gunmetal. AB - Gunmetal (gm/gm) is a recessively inherited mouse pigment dilution mutant that has high mortality and poor reproductive rates. In these studies, several hematologic defects were found associated with the mutation, including prolonged bleeding times, together with thrombocytopenia and increased platelet size. A unique feature is the presence of simultaneous abnormalities in two platelet organelles, dense granules and alpha-granules. The dense granule component serotonin is present at about half the normal concentration, as are visible dense granules. Three alpha-granule components (fibrinogen, platelet factor 4, and von Willebrand factor) are also significantly reduced. Thus, in several respects the gunmetal mutant resembles the human gray platelet syndrome. A novel abnormality in expression of low molecular weight guanosine triphosphate (GTP)-binding proteins occurs in platelets of gunmetal. In Western blot assays, two additional GTP-binding proteins of 28.5 and 25 Kd were detected. The abnormal expression of GTP-binding proteins is, like the hematologic defects, genetically recessive and is tissue specific. Liver, kidney, brain, spleen, macrophages, and neutrophils have normal GTP-binding protein expression. The additional GTP-binding proteins are soluble. The data indicate that platelet formation and platelet organelle biogenesis are under common genetic control and that abnormal regulation of GTP binding proteins may affect one or both processes. PMID- 8490172 TI - Characterization of ultrasound-potentiated fibrinolysis in vitro. AB - We have characterized the effects of ultrasound on fibrinolysis in vitro to investigate the mechanism of ultrasonic potentiation of fibrinolysis and to identify potentially useful ultrasound parameters for therapeutic application. Radiolabeled clots in thin walled tubes were exposed to ultrasound fields in a water bath at 37 degrees C, and lysis was measured by solubilization of radiolabel. Ultrasound accelerated lysis of plasma, whole blood, and purified fibrin clots mediated by recombinant tissue-type plasminogen activator (rt-PA), urokinase, or streptokinase, but ultrasound by itself caused no clot solubilization. The degree of ultrasonic potentiation was dependent on plasminogen activator concentration, increasing from 2.2-fold at a streptokinase concentration of 75 U/mL to 5.5-fold at 250 U/mL in a 1 MHz ultrasound field at 4 W/cm2. Ultrasound exposure resulted in heating due to absorption by the plastic tube, but the temperature increase was insufficient to account for the increase in clot lysis rate, indicating that the primary effect was nonthermal. Ultrasound did not accelerate hydrolysis of a peptide substrate by rt-PA and did not alter the rate of plasmic degradation of fibrinogen, indicating that the augmentation of enzymatic fibrinolysis required the presence of a fibrin gel. The acceleration of fibrinolysis by ultrasound was greater at higher intensities and duty cycles and was maximum at frequencies between 1 and 2.2 MHz, but decreased at 3.4 MHz. These findings suggest that ultrasound accelerates enzymatic fibrinolysis by increasing transport of reactants through a cavitation-related mechanism. PMID- 8490173 TI - The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A. AB - We have studied the roles of von Willebrand factor (vWF) and factor VIII in arterial thrombosis in four canine phenotypes: normal (n = 6), hemophilia A (n = 11), von Willebrand disease (vWD) (n = 9), and hemophilia A/vWD (n = 1). vWF activity was determined by botrocetin-induced agglutination of fixed human platelets and vWF antigen (vWF:Ag) by Laurell electroimmunoassay and crossed immunoelectrophoresis. Plasma from normal dogs and those with hemophilia A had vWF activity, vWF:Ag, and a full range of vWF:Ag multimers on gel electrophoresis equivalent to normal canine plasma pool. Platelet cytosol contents were isolated by freezing and thawing, triton X-100 solubilization, or sonication of washed platelets with and without protease inhibitors and inhibitors of platelet activation. Washed platelets were also stimulated with calcium ionophore and MgCl2. There was no measurable vWF activity or vWF:Ag in platelet lysates or releasates in any dog regardless of phenotype. All dogs were studied using a standard arterial stenosis and injury procedure to induce arterial thrombosis. Thromboses were detected by cyclic reductions in Doppler blood flow velocity. Vessels were examined by light and scanning electron microscopy. Thrombosis developed in the arteries of normal (9 of 10) and hemophilia A dogs (16 of 16) but in none of the vWD dogs (0 of 10). Infusion of canine vWF cryoprecipitate into vWD dogs markedly shortened bleeding time but did not support thrombosis as seen in dogs with vWF in the plasma and subendothelium. Thrombosis, then, fails to occur when vWF is absent from the plasma and subendothelial compartments or present only in the plasma compartment. These data are consistent with the hypothesis that vWF in the plasma and subendothelium supports thrombosis. Neither plasma FVIII nor platelet vWF is essential for thrombosis in this model. PMID- 8490174 TI - Adenosine diphosphate stimulation of cultured hematopoietic cell lines. AB - Adenosine diphosphate (ADP) plays a critical role in platelet activation both by exogenous stimulation and the release of endogenous intracellular stores. As the platelet ADP receptor is not well defined, we have chosen to identify and characterize several cell lines that possess functional receptors for this nucleotide. Rat promegakaryoblasts (RPM), human erythroleukemia cells (HEL), U937, and K562 leukemia cells responded to ADP, as measured by a rapid increase in intracellular calcium. In the case of RPM cells, ADP was the only naturally occurring platelet agonist capable of eliciting this response. Binding studies with [3H]ADP and fixed cells showed 3.99 +/- 1.77 x 10(5) binding sites/cell for RPM cells (apparent dissociation constant [kd] = 7.75 +/- 2.3 x 10(-8) mol/L), 8.19 +/- 3.25 x 10(5) sites/cell for HEL cells (kd = 2.15 +/- 0.84 x 10(-7) mol/L, 1.15 +/- 0.23 x 10(6) sites/cell for U937 cells (kd = 2.20 +/- 0.53 x 10( 7) mol/L) and 5.39 +/- 2.80 x 10(5) sites/cell for K562 cells (kd = 1.37 +/- 0.39 x 10(-7) mol/L), Inhibition studies with unlabeled nucleotides and analogues showed that binding was approximately 85% specific and the inhibitory pattern was similar to that seen with mature platelets. The purine base adenosine resulted in little or no inhibition. These studies indicate that both human and rat hematopoietic cell lines possess intact ADP receptors and may be useful tools in future studies of the structure and function of this important platelet activation system. PMID- 8490175 TI - Phenotypic difference of normal plasma cells from mature myeloma cells. AB - We have recently shown that two-color analysis with fluorescein isothiocyanate (FITC)-anti-CD38 antibody could clearly distinguish myeloma cells (plasma cells) from other hematopoietic cells in the bone marrow. Myeloma cells (plasma cells) alone were located at CD38strong positive (++) fractions. To further distinguish normal plasma cells from mature myeloma cells phenotypically, we examined immunophenotypes of normal plasma cells and myeloma cells by two-color flow cytometry with FITC-anti-CD38 antibody and phycoerythrin staining with antibody to VLA-4, MPC-1, CD44, CD56, CD19, CD20, CD24, or CD10. Normal plasma cells were all VLA-4+VLA-5+MPC-1+CD44+ CD19+CD56- in the bone marrows from seven healthy donors, tonsils from four patients with chronic tonsillitis, a spleen from one patient with idiopathic thrombocytopenic purpura, and lymph nodes from two patients with chronic lymphadenitis, respectively. On the other hand, mature myeloma cells (12 of 20 cases), VLA-4+VLA-5+MPC-1+, were all CD19- and most of them CD56+, and there were no myeloma cells with the CD19+CD56- phenotype in the 20 cases of myelomas we tested. Thus, as for the expression of CD19 and CD56, normal plasma cells from various tissues are all CD19+CD56-, whereas no myeloma cells have the CD19+CD56- phenotype. According to this finding, we investigated the expression of CD19 and CD56 on plasma cells (CD38++ fractions) in monoclonal gammopathy of undetermined significance (MGUS). Both CD19+CD56- and CD19-DC56+ plasma cells were found in all five cases of MGUS we tested, suggesting that MGUS consists of phenotypically normal plasma cells and myeloma cells. Therefore, it is reasoned that phenotypic analysis of plasma cells with anti-CD19 and anti-CD56 antibodies can distinguish normal plasma cells from malignant plasma cells (myeloma cells), and can detect malignant plasma cells even in MGUS or premyeloma states. PMID- 8490176 TI - Human megakaryocytes have a CD4 molecule capable of binding human immunodeficiency virus-1. AB - Most human megakaryocytes (MGKs) express the CD4 antigen on their surface. Approximately 25% have a CD4 receptor density comparable to that of CD4+ T cells (Basch et al, Proc Natl Acad Sci USA 87:8085, 1990). In these studies, we show: (1) the presence of mRNA for CD4 in human MGKs; (2) the binding of human immunodeficiency virus-1 (HIV-1) to human MGKs; (3) the inhibition of binding by anti-CD4 (Leu3a) antibody or rCD4; (4) the infection of a human MGK line, CHRF 288 with HIV-1; and (5) inhibition of infection with anti-CD4. Human MGKs have mRNA for CD4 as shown by in situ hybridization with an RNA probe synthesized from a 3-kb cDNA sequence of plasmid pSP65.T4.8 containing the full-length CD4 sequence. MGKs (23% +/- 17%) bound HIV-1, as determined by anti-gp120 and anti CD41 staining. Binding to human MGKs could be inhibited 55% to 75% with anti-CD4 or rCD4, respectively. Infection of a CD4+ MGK line (CHRF-288) could be accomplished with HIV-1, as determined by proviral DNA polymerase chain reaction and p24 production. Preincubation with anti-CD4 inhibited apparent proviral DNA infection by 100% and p24 production by 65% to 70%. Thus, human MGKs have a CD4 receptor capable of binding HIV-1. Using this receptor, HIV-1 can infect cells representative of the MGK lineage. PMID- 8490177 TI - Effect of granulocyte-macrophage colony-stimulating factor on lymphokine activated killer cell induction. AB - The treatment of cancer with lymphokine-activated killer (LAK) cells in conjunction with high-dose interleukin-2 (IL-2) has been limited by the toxicity of IL-2 and the narrow range of tumors that respond to therapy. Cytokines that are capable of augmenting lower doses of IL-2 are, therefore, a major focus of research. We report here that granulocyte-macrophage colony-stimulating factor (GM-CSF) can augment low-dose IL-2 LAK induction from murine splenocytes. Anti tumor necrosis factor alpha (anti-TNF alpha) or anti-interferon gamma (anti-IFN gamma) monoclonal antibodies did not inhibit (IL-2 + GM-CSF)-induced LAK generation, indicating that GM-CSF augmentation does not require TNF alpha or IFN gamma activity. Depletion of natural killer cells before culture did not inhibit low-dose IL-2-induced LAK generation or the ability of GM-CSF to augment LAK generation. In contrast, depletion of both CD4+ and CD8+ T cells before culture inhibited the generation of LAK activity. However, depletion of only CD4+ T cells, or only CD8+ T cells, did not inhibit the generation of IL-2 or (IL-2 + GM CSF) LAK activity. These results suggest that LAK precursors are present in both the CD4+ and CD8+ T-cell populations and suggest that the addition of GM-CSF to low-dose IL-2 may result in the generation of T-derived LAK cells. PMID- 8490178 TI - DCC tumor suppressor gene is inactivated in hematologic malignancies showing monosomy 18. AB - DCC (deleted in colorectal cancer) is a candidate tumor suppressor gene recently identified on chromosome band 18q21. Loss of one DCC allele or decreased DCC expression occurs in more than 70% of colorectal cancers, suggesting that DCC inactivation constitutes a critical event in the development of these tumors. Using polymerase chain reaction amplification of cDNA, we have studied DCC expression in bone marrow from 4 patients with leukemia (1 chronic myeloid leukemia-blastic crisis, case 1; 1 acute myeloid leukemia, case 2; 1 T-cell acute lymphoblastic leukemia [ALL], case 3; 1 B-cell ALL, case 4) showing loss of one DCC allele due to monosomy 18. We also studied DCC expression in multiple control samples, including normal lymphocytes, normal tonsillar tissue, and leukemias without 18q abnormalities. Four primer pairs consistently amplified the predicted DCC sequences from cDNA prepared from all control samples. However, in samples with monosomy 18, DCC transcripts were either not detected (case 1) or detected at a very low level (cases 2, 3, and 4). Southern analysis showed no structural rearrangement of the remaining DCC locus in all leukemia samples. Thus, loss of DCC expression was demonstrated in association with loss of one DCC allele in all cases tested. These results suggest that, as for colorectal tumors, the inactivation of DCC can have a role in the development of hematologic malignancies. PMID- 8490179 TI - Mutational activation of N- and K-ras oncogenes in plasma cell dyscrasias. AB - The frequency of N- and K-ras oncogene mutations was investigated in plasma cell dyscrasias. Genomic DNAs from 128 patients were selected for this study: 30 monoclonal gammopathies of undetermined significance, 8 solitary plasmacytomas, 77 multiple myelomas (MM), and 13 plasma cell leukemias (PCL). A two-step experimental approach was devised. All samples were screened for mutations by single-strand conformation polymorphism analysis. DNA fragments displaying an altered electrophoretic mobility were further studied by direct sequencing to confirm and characterize the nature of the mutations. Ras mutations are not randomly distributed because they are detectable only in MM (9%) and PCL (30.7%). N-ras codons 12, 13, and 61 and K-ras codon 12 were found to be mutated, but N ras codon 61 mutation was the most frequent finding (63.6%). In conclusion, ras mutations were found in PCL, and in a subset of MM characterized by advanced stage disease and adverse prognostic parameters. Furthermore, based on our findings, it is possible to speculate that ras mutations represent a late molecular lesion in the process of multistep carcinogenesis. PMID- 8490180 TI - Establishment of a karyotypically normal cytotoxic leukemic T-cell line from a T ALL sample engrafted in SCID mice. AB - Bone marrow (BM) cells from a child with an immature (CD3-) acute T lymphoblastic leukemia (T-ALL) bearing no chromosomal abnormalities failed to grow in long-term culture in the presence or absence of recombinant human (rh) growth factors but could be engrafted in severe combined immunodeficient (SCID) mice and induced leukemia. The leukemic cells recovered from the animal tissues could be adapted to grow in vitro in the presence of rh interleukin-2 (IL-2) and give rise to a growth factor-dependent cell line designated TALL-107. This cell line expresses T cell-specific mature markers (CD2, CD3/T-cell receptor [TCR] alpha beta, CD8, CD56), and its growth can be inhibited by IL-4 of all the cytokines tested. Similar to the original leukemic blasts, TALL-107 cells are clonal, have rearranged TCR-beta, gamma, and delta loci, and a normal 46 XY karyotype. However, unlike the patient's BM cells, the TALL-107 cell line displays potent tumoricidal activity that is not major histocompatibility complex restricted. The magnitude of mRNA expression of perforin and serine esterases and of lytic activity depends on the doses of IL-2 added. TALL-107 cells can also be triggered by CD3- and CD2-specific monoclonal antibodies (MoAbs) to mediate reverse tumor cell lysis. In addition, this cell line produces high levels of interferon gamma and tumor necrosis factor alpha on stimulation with anti-CD3 and/or anti-CD2 MoAb both in the presence or absence of IL-2. The overall data indicate that the SCID mouse is able to support the functional maturation and expansion of a cytotoxic T cell subset from some types of T-ALL. PMID- 8490181 TI - Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. AB - A nonrandom translocation between chromosomes 3 and 21, t(3;21)(q26.2;q22) has been detected in patients with a myelodysplastic syndrome or acute myeloid leukemia after treatment (t-MDS/t-AML) for a primary malignant disease and in chronic myelogenous leukemia in blast crisis (CML-BC). In these patients, the breakpoint on chromosome 21 is at band 21q22. This band is also involved in the t(8;21)(q22;q22) detected in 40% of the patients with acute myeloid leukemia subtype M2 (AML-M2) de novo who have an abnormal karyotype. In the t(8;21), the AML1 gene is the site of the breakpoint on chromosome 21. The AML1 gene is transcribed from telomere to centromere, and in the t(8;21) the 5' part of AML1 is fused to the ETO gene on chromosome 8 to produce the chimeric AML1/ETO on the der(8) chromosome. We found that AML1 is also rearranged in two t-AML patients and in one CML-BC patient with the t(3;21), but the breakpoints are approximately 40 to 60 kb downstream to those of AML-M2 patients. This region contains at least one additional exon of AML1, as determined by using an AML1 cDNA as a probe in Southern blot analysis. The t(3;21) breakpoints for the remaining patients could not be determined because, by fluorescence in situ hybridization analysis, the breaks are outside of the region covered by the available probes. PMID- 8490182 TI - Mechanisms for actin reorganization in chemotactic factor-activated polymorphonuclear leukocytes. AB - Cytoskeletal structure in polymorphonuclear leukocytes (PMNs) is thought to reflect a simple equilibrium between two actin pools (globular [G]- and filamentous [F] actin). Recent description of two distinct F-actin pools in PMNs (Triton-insoluble [stable] and Triton-soluble [labile] F-actin pools) (Watts and Howard, Cell Motil Cytoskeleton, 21:25, 1992) suggest a tripartite equilibrium between these F-actin pools and G-actin and multiple possible mechanisms for polymerization. To study the contribution of each actin pool to actin dynamics in PMNs, changes in actin content of the Triton-soluble and -insoluble F-actin pools and G-actin in chemotactic factor (CTF)-activated PMNs were measured by NBDphallacidin binding and by gel scans of Triton-lysed PMNs. From 0 to 30 seconds after CTF activation, PMNs rapidly increase total (Triton-soluble + Triton-insoluble) F-actin content (maximum = 1.7- +/- 0.10-fold basal at 30 seconds). Concurrent measures of the actin content of individual actin pools (Triton-soluble and -insoluble F-actin and G-actin) show that at all times (0 to 30 seconds) only the Triton-insoluble F-actin pool grows (maximum = 2.81- +/- 0.73-fold basal at 30 seconds), whereas both the Triton-soluble and G-actin pools simultaneously decrease (50% decrease at 30 seconds). Concurrent growth of one F actin pool (Triton-insoluble) and loss of another F-actin pool (Triton-soluble) emphasize the functional uniqueness of the F-actin pools and can occur only if the Triton-soluble F-actin anneals or cross-links filament-to-filament with the Triton-insoluble fraction or if the Triton-insoluble F-actin pool first depolymerizes to monomer, which is then added to the Triton-insoluble pool. Because from 0 to 30 seconds after FMLP activation G-actin never increases, but, like the Triton-soluble F-actin progressively decreases, the results suggest that F-actin growth results from simultaneous new filament growth by monomer addition to the Triton-insoluble F-actin and cytoskeletal remodelling by Triton-soluble F actin annealing or cross-linking to Triton-insoluble F-actin. These findings offer important new insights into the mechanism(s) of actin polymerization in CTF activated human PMNs. PMID- 8490183 TI - Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes. AB - Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a polypeptide mediator, elaborated by certain tumors and other cell types, that exerts multiple effects on endothelium via interaction with a class of high affinity binding sites. In this report, the interaction of VPF/VEGF with human mononuclear phagocytes (MPs) is characterized. Radioligand binding studies at 4 degrees C showed the presence of a single class of binding sites, kd approximately 300 to 500 pmol/L (approximately 20 times lower affinity than the high-affinity binding site on endothelial cells [ECs]), the occupancy of which correlated with VPF/VEGF-induced MP migration and expression of tissue factor. These binding results were paralleled by functional experiments which indicated that the same VPF/VEGF preparations were about an order of magnitude less effective in stimulating MP chemotaxis than in inducing EC proliferation. When MPs with surface-bound 125I-VPF/VEGF were warmed to 37 degrees C, endocytosis and degradation occurred. Occupancy of VPF/VEGF binding site resulted in subsequent activation of intracellular signal transduction mechanisms, as shown by an increase in MP intracellular calcium concentration. Cross-linking studies with 125I-VPF/VEGF showed a new high-molecular weight band (corresponding to putative 125I-VPF/VEGF-receptor complex), the appearance of which was blocked by excess unlabeled VPF/VEGF. Consistent with these results, immunoprecipitation of 32PO4 labeled MPs exposed to VPF/VEGF showed a single band of similar mobility, not seen in untreated controls. These results demonstrate that the interaction of VPF/VEGF with MPs, though of lower affinity than that observed with ECs, also results from interaction of the polypeptide with a specific cell-surface protein and leads to activation of intracellular transduction mechanisms. PMID- 8490184 TI - Volume and osmotic properties of human neutrophils. AB - Quantitative models describing the dynamics of human neutrophils in the microcirculation require accurate morphometric parameters such as volume and surface membrane area. Using both a micropipette technique and video light microscopy (LM) to measure the diameters of the spherical cells, we have accurately determined the volume of the human neutrophil. Our value, 299 +/- 32 microns 3, is in good agreement with our earlier results, but 55% larger than that reported by Schmid-Schonbein et al (Blood 56:866, 1980). However, the measurements of Schmid-Schonbein et al were based on the actual mass of the cells derived from transmission electron microscopic (TEM) images. The membrane surface area, at lysis, was calculated to be 2.6 times its initial projected area. After lysis, the cells do not reduce their size, indicative of the possibility of a F actin network formation that would stiffen the structure. Further, we show that neutrophils behave as ideal osmometers when exposed to anisotonic solutions at 21 degrees C, as predicted by the Boyle-Van't Hoff relationship. The calculated Ponder's value, R, is 0.77, which corresponds to 77% of the cell volume being osmotically active under isotonic conditions. However, at 37 degrees C, the cells are able to regulate their volumes toward the original volumes after an osmotic stress. PMID- 8490185 TI - Characterization of the DNase I hypersensitive site 3' of the human beta globin gene domain. AB - The members of the human beta globin gene family are flanked by strong DNase I hypersensitive sites. The collection of sites 5' to the epsilon globin gene is able to confer high levels of expression of linked globin genes, but a function has not been assigned to the site 3' to the beta globin gene (3'HS1). Our analysis of this DNase I super hypersensitive site shows that the region is composed of multiple DNase I sites. By examination of the DNA sequence, we have determined that the region is very A/T-rich and contains topoisomerase II recognition sequences, as well as several consensus binding motifs for GATA-1 and AP-1/NF-E2. Gel mobility shift assays indicate that the region can interact in vitro with GATA-1 and AP-1/NF-E2, and functional studies show that the region serves as a scaffold attachment region in both erythroid and nonerythroid cell lines. Whereas many of the physical features of 3'HS1 are shared by 5'HS2 (a component of the 5' locus control region), transient expression studies show that 3' HS1 does not share the erythroid-specific enhancer activity exhibited by 5'HS2. PMID- 8490186 TI - A splice site mutation of alpha-spectrin gene causing skipping of exon 18 in hereditary elliptocytosis. AB - Spectrin Oran (alpha II/21) has been reported previously as a variant of the alpha II domain. Its expression level is low (10% of total spectrin) in heterozygotes denoting a major disadvantage of the mutated alpha-chain dimer or tetramer with respect to their normal counterparts. Spectrin Oran is associated with symptomatic elliptocytosis in the homozygous state. A 1-minute digestion time allowed to perceive a fast trypsin cleavage (not existing normally) after Arg 890 (helix 3 of repeating segment alpha 9). The responsible change was the lack of amino acids 822 to 862 (helix 2 of repeating segment alpha 8). Such a situation fits with the phasing of spectrin according to which mutated helix 2 and distorted helix 3 are adjacent to one another. The internal position of the structural change accounts for the slight self-association defect. The ultimate genetic lesion was a G to A substitution (intronic position-1) in the acceptor splice site of intron 17 resulting in skipping of exon 18. The substitution also created an acceptor splice site 1 base downstream, but the latter was used at a low grade. PMID- 8490187 TI - Infusional cyclophosphamide, doxorubicin, and etoposide in human immunodeficiency virus- and human T-cell leukemia virus type I-related non-Hodgkin's lymphoma: a highly active regimen. AB - Fourteen patients with poor-prognosis intermediate- to high-grade non-Hodgkin's lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection (12 patients) or human T-cell leukemia virus type I (HTLV-I) infection (two patients) received cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and etoposide 240 mg/m2 administered as a continuous intravenous (IV) infusion over 4 days (infusional CDE); treatment was repeated every 28 or more days for up to six cycles. All HIV-positive patients had at least one poor prognostic feature, which included either extranodal disease (10 patients), Karnofsky performance status less than 70% (six patients), a CD4 count less than 100/microL (six patients), or a prior history of acquired immunodeficiency syndrome (AIDS; one patient). Both HTLV-I-positive patients had an elevated serum lactate dehydrogenase (LDH) level, a poor prognostic feature in that setting. Complete response (CR) occurred in 10 patients (71%; 95% confidence interval, 48% to 95%) and partial response (PR) occurred in three patients (21%), yielding an overall objective response rate of approximately 93%. The estimated Kaplan-Meier median survival was 17.4 months; seven of 12 HIV-positive patients are alive and disease-free with a median follow up of 15 months (range, 7 to 24 months). Hospitalization was required after 19% of treatment cycles due to fever associated with granulocytopenia. Documented or suspected opportunistic infection occurred in five patients (36%), bacteremia occurred in three patients (21%), and candidemia occurred in one patient (7%). There was one treatment-related death attributable to disseminated aspergillosis. This pilot study suggests that infusional CDE may be a highly active regimen capable of producing durable remissions in a high proportion of patients with HIV related NHL. Further study is required to confirm this observation. PMID- 8490188 TI - Autoreactive T-cell-dependent polyclonal B-cell differentiation in mantle zone lymphoma. PMID- 8490189 TI - Macrophage colony-stimulating factor: serum levels and cDNA structure in malignant osteopetrosis. PMID- 8490190 TI - A new, striking morphologic feature for the human erythrocyte in hereditary spherocytosis: the blebbing pattern. PMID- 8490191 TI - Cancer cachexia. AB - Cachexia is a common problem in the clinical management of cancer patients, particularly those with solid tumors. Cachexia is most obviously manifested as weight loss with massive depletion of both adipose tissue and muscle mass, and death is probably due to loss of lean body tissue. Not only is the survival time shorter in patients with cachexia, but the frequency of response to chemotherapy is also significantly reduced. Although anorexia frequently accompanies cachexia, attempts to halt or reverse cachexia by nutritional repletion have not been successful. This suggests that cachexia is due to metabolic abnormalities produced by the tumor in addition to the underlying anorexia. In some patients weight loss is associated with an increased relative energy expenditure possibly through an elevated adrenergic state. Several factors have been postulated as mediators of cancer cachexia and can be divided into two groups. (i) Materials with hormone-like characteristics which result in direct catabolism of host tissues. (ii) Cytokines which cause alterations in host metabolism indirectly. Included in group (i) are the conventional catabolic hormones and a lipid mobilizing factor (LMF) produced by tumors, which causes direct breakdown of adipose tissue. Included in group (ii) are tumor necrosis factor-alpha, interleukin-6, interferon-gamma and leukaemia inhibitory factor. The materials appear to influence adipose tissue indirectly through an inhibition of lipoprotein lipase. Reversal of cachexia has been achieved by two groups of agents. (i) Those stimulating food intake, e.g. megestrol acetate. (ii) Those directly inhibiting the LMF, e.g. eicosapentaenoic acid. While agents in group (i) can cause tumor growth stimulation, those in group (ii) act as tumor growth inhibitors. This latter results suggests that the products of catabolism of host tissues may be important for tumor growth and provides a new avenue for chemotherapeutic intervention. PMID- 8490192 TI - Can hematopoietic growth factors be used to improve the success of cytotoxic chemotherapy? AB - Hematopoietic growth factors (HGFs) have provided oncologists with powerful tools to investigate questions of chemotherapy dose and treatment outcome in cancer patients. Agents such as recombinant granulocyte colony-stimulating factor (e.g. G-CSF; filgrastim) significantly accelerate neutrophil recovery after chemotherapy and therefore allow the delivery of a planned dose on time. Moreover, it is possible to investigate the effects of escalated dose chemotherapy with HGF support. This can be done using the HGF alone or in conjunction with stem cell rescue. HGFs significantly reduce morbidity following bone marrow transplantation (BMT) and may also be used to mobilize peripheral blood progenitor cells (PBPC) to support high-dose chemotherapy. Growth factor mobilized PBPC have practical and clinical advantages over BMT and may be a more effective method of allowing the delivery of high-dose therapy, but for some patients (who for reasons not yet clear, display a poor mobilization response) a combination of autologous bone marrow and PBPC might be more effective at reconstituting hematopoiesis. Whether more intensive treatment approaches will significantly improve survival remains to be determined. PMID- 8490193 TI - Cisplatin and carboplatin induced changes in the neurohypophysis and parathyroid, and their role in nephrotoxicity. AB - Cytochemical and ultrastructural studies in Wistar rats [Crl: (WI)BR] show that cisplatin treatment (5-9 mg/kg) induces a release of neurosecretory granules from the neurohypophysis with a corresponding decrease in the urine output in a time and dose dependent fashion. Cisplatin induces low blood calcium and phosphate levels with a corresponding increase in the dark cells of the parathyroid gland. Injections of calcium before and during the treatment of cisplatin are effective in combating hypocalcemia, nephrotoxicity and gastrointestinal toxicity due to cisplatin. Carboplatin, a less nephrotoxic agent, does not demonstrate any of these changes. PMID- 8490194 TI - A phase I trial of trimetrexate (NSC352122) on a daily x 5 schedule in patients with refractory adult leukemia. AB - Seven adult patients with refractory acute leukemia were administered trimetrexate (TMTX), a non-classical folate antagonist, in a phase I trial. TMTX was administered as an intravenous bolus for five consecutive days at doses of 9 12 mg/m2 based on marrow response. The maximum tolerated dose was 12 mg/m2. Hepatotoxicity was the dose-limiting toxicity. Initial dosage reductions in patients with liver disease and/or low protein concentrations may be necessary since TMTX is significantly protein bound and cleared primarily by hepatic metabolism. The recommended phase II dose on this dosing schedule is 9 mg/m2. PMID- 8490195 TI - Antitumor activity of a new series of platinum complexes: trans(+/-)-1,2 cyclohexanediammineplatinum(II) conjugated to acid polysaccharides. AB - Complexes with trans(+/-)-1,2-cyclohexanediammineplatinum(II) conjugated to acid polysaccharides were synthesized and their antitumor activities were tested in female CDF1 mice with intraperitoneal leukemia L1210 cells. Platinum was released from the polymers under physiological conditions, with half-lives from 3.3 to 19.3 h. A hyaluronic acid-supported complex was the most effective against the tumors (all six mice survived for 60 days). The group given a chondroitin polysulfate-supported complex had five survivors, the chondroitin sulfate A group also had five, the chondroitin sulfate C group had three and the heparan sulfate group had two. Part of the antitumor activity was due to increased efficacy of the polymers. The bioavailability of these complexes is high. Therefore, acid polysaccharides should be a good system for delivering antitumor platinum complexes. PMID- 8490196 TI - Reduced bone marrow toxicity of KW-2149, a mitomycin C derivative, in mice. AB - The bone marrow toxicity of KW-2149, a newly synthesized mitomycin C (MMC) derivative, was compared with MMC in different aged ddY mice. Both MMC and KW 2149 exhibited a similar type of leukopenia in young adult mice. However, in mature adult mice, the recovery from leukopenia was rapid in KW-2149-treated mice, whereas in the MMC-treated mice, it was delayed. The difference between KW 2149 and MMC was more significant in thrombocytopenia in mature mice, and that induced by KW-2149 was mild, whereas that by MMC was severe and delayed. This reduced bone marrow toxicity of KW-2149 in mature mice was confirmed by the assay of colony-forming units in culture, progenitors of granulocytes or macrophages, and megakaryocytic colony-forming units, progenitors of platelets, in the bone marrow cells. The bone marrow toxicity and lethal toxicity of MMC was augmented by weekly intermittent treatment; in contrast, that of KW-2149 was not, suggesting that bone marrow toxicity may have a critical role in the lethal toxicity of MMC. The non-cumulative bone marrow toxicity of KW-2149 enabled the weekly intermittent treatment of human lung adenocarcinoma L-27 inoculated into nude mice. Thus its antitumor activity was greater than with single treatment. PMID- 8490197 TI - A preliminary report of a pilot randomized trial comparing cyclophosphamide, methotrexate and 5-fluorouracil with cyclophosphamide, mitoxantrone and 5 fluorouracil in the adjuvant therapy of stage II breast cancer with four or more positive axillary nodes. AB - Thirty-eight patients with stage II breast cancer with four or more positive axillary lymph nodes were randomized to receive CMF (cyclophosphamide, methotrexate and 5-fluorouracil, every 3 weeks) or CXF (cyclophosphamide, mitoxantrone and 5-fluorouracil, every 3 weeks). Pretreatment characteristics were similar for both groups. The actuarial 5 year disease-free survival (DFS) was 36% for the CMF group and 23% for the CXF group. The actuarial 5 year survival was 60% for the CMF arm and 66% for the CXF arm. These differences were not statistically significant. Partial alopecia was observed in 42% of patients in the CMF arm and in 100% of those receiving CXF (p = 0.0002). No episodes of leucopenic fever were observed in patients receiving CMF, while they were present in 53% of patients treated with CXF (p = 0.0006). No stomatitis occurred in the CMF group, but it was observed in 90% of patients who received CXF (p < 0.0001). Treatment with CXF had to be discontinued in two patients because of toxicity. In this small group of patients with poor prognosis, it seems that CXF at the doses given here is more toxic but not more effective than CMF, as represented by a similar DFS and survival. PMID- 8490198 TI - Intratunical injection of methotrexate for the treatment of seminoma of the testicle. AB - A bilateral testicular seminoma in a 32 year old man is reported. The patient was unmarried and refused bilateral orchidectomy for its sterile result. He was treated with four courses of methotrexate (MXT) injected in the tunica vaginalis sac. Each course comprised the administration of 50 mg MXT in each tunical sac every 5 days for five consecutive doses followed by 3 weeks rest. No toxicity was encountered. Testicular biopsy 6 months after the start of treatment was negative for malignant cells. A temporary drop of sperm count occurred during treatment. Treatment was performed 6 years ago, and the patient has had no recurrence and is fertile. The treatment was done on an outpatient basis. PMID- 8490199 TI - Oligonucleotide degradation contributes to resistance to antisense compounds. AB - A subline of the human B cell lymphoma DHL-4, grown in the artificial serum-free medium HB101, displayed a resistant phenotype to the activity of an antisense oligodeoxynucleotide (aODN) effective on the parental DHL-4 line. It was found that the cellular uptake of the 18mer aODN in the two cell lines was almost the same. In contrast, the unresponsive subline DHL-4r degraded the aODN very efficiently, in contrast to the stability of aODN inside cells of the parental DHL-4 line. Activation of the degrading 'machinery' combined with selective properties of the artificial medium may be responsible for the loss of responsiveness to aODN. PMID- 8490200 TI - Inhibition of c-myc in breast and ovarian carcinoma cells by 1,25 dihydroxyvitamin D3, retinoic acid and dexamethasone. AB - The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitriol, RA and Dex have anti-proliferative activity in breast and gynecologic carcinoma cells; however, the regulation of c-myc by these agents in breast and ovarian cancers is mostly unknown. We have addressed the regulation of c-myc in these cancers using an adaptation of a novel method which employs an immunohistochemical procedure to detect c-myc protein followed by quantification of c-myc staining with computerized image analysis. This system represents an alternative to protein product assay by Western blotting and is straightforward, rapid (1 day), can be carried out on a small scale and provides a sample size that readily facilitates statistical analysis of assay data. In MCF-7 human breast cancer cells, c-myc was suppressed 29% by 0.5 nM Dex, 45% by 0.01 nM RA and 54% by 100 nM calcitriol after 24 h of drug treatment. At the same hormone concentrations, growth was inhibited 18% by Dex, 18% by RA and 39% by calcitriol after 3 days of treatment (p < 0.05 for all hormones). Similar patterns of growth and c-myc inhibition were seen in T47D human breast cancer cells and NIH:OVCAR3 human ovarian cancer cells, with the exception of Dex in T47D cells, which caused no inhibition of c-myc or growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490201 TI - Immunomodulatory effects of a polysaccharide from Tamarindus indica. AB - A polysaccharide isolated and purified from Tamarindus indica shows immunomodulatory activities such as phagocytic enhancement, leukocyte migration inhibition and inhibition of cell proliferation. These properties suggest that this polysaccharide from T. indica may have some biological applications. PMID- 8490202 TI - The cytotoxicity of heterocyclic thiosemicarbazones and their metal complexes on human and murine tissue culture cells. AB - Heterocyclic thiosemicarbazones, thioureas and 2-substituted pyridine N-oxides as well as representative nickel, cobalt and copper complexes were shown to be potent antineoplastic/cytotoxic agents. The cytotoxicity was demonstrated against single cell leukemia as well as cell lines derived from solid tissue (colon adenocarcinoma, HeLa, KB, skin, bronchogenic lung, bone osteosarcoma and glioma). In L1210 cells, DNA synthesis and subsequently RNA synthesis were particularly inhibited by the agents. IMP dehydrogenase activity and thus purine de novo synthesis was reduced significantly by the agents. Dihydrofolate reductase, ribonucleoside reductase, nucleoside kinase and DNA polymerase alpha activities were inhibited by the agents. d(NTP) pool levels were reduced by most of the agents. DNA strand scission was present with all of the derivatives; however, there was no evidence of intercalation, cross linking or alkylation/binding to bases of DNA. This new group of compounds may offer novel exploratory derivatives for future investigations in the treatment of cancer. PMID- 8490203 TI - Differential cytotoxicity, uptake and DNA binding of tetraplatin and analogous isomers in sensitive and resistant cancer cell lines. AB - Some platinum complexes contain 1,2-diaminocyclohexane (DACH) as a stable carrier ligand, which can exist as the R,R-, S,S- and cis-isomers. Tetraplatin, for instance, is a mixture of R,R- and S,S-DACH-Cl4-Pt(IV). We have examined each of the three individual isomers of DACH-Cl4-Pt(IV) with respect to cytotoxicity, uptake of platinum and total DNA-platinum in three murine leukemia L1210 (cisplatin-sensitive L1210/0, 50-fold cisplatin-resistant L1210/DDP and 36-fold tetraplatin-resistant L1210/DACH) and human ovarian carcinoma A2780 (cisplatin sensitive) and A2780cp (8-fold cisplatin-resistant) cell lines. Against A2780, A2780cp and L1210/DDP cell lines, the R,R-isomer was the most potent followed by the S,S-isomer and then the cis-isomer. However, the three isomers demonstrated similar IC50 values against the L1210/0 and L1210/DACH cell lines. The cis-isomer demonstrated cross-resistance (9- to 20-fold) to cisplatin in L1210/DDP and A2780cp cell lines. On the other hand, R,R- and S,S-isomers demonstrated minimal (2- to 4-fold) cross-resistance against these tumor models. Intracellular platinum accumulation over a 2 h period at 40 microM drug concentration was significantly (p < 0.05) greater for the R,R-isomer than the cis-isomer in L1210/0 (122 versus 101 ng Pt/mg protein) and L1210/DDP (73 versus 50) cell lines, while no difference was observed in L1210/DACH cells (55 versus 56). In L1210/DDP cells, total DNA-bound platinum was significantly (p < 0.05) greater for the R,R-isomer compared with the cis-isomer (10.3 versus 7.5 ng Pt/mg DNA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490204 TI - Sodium butyrate inhibits rat insulinoma cell proliferation without affecting the cellular insulin content or insulin release. AB - The short-chain carboxylic acid sodium butyrate is known to induce differentiation in several cell systems. In this paper we have investigated the effect of sodium butyrate on the growth rate and hormone content and secretion in clonal rat insulinoma cells (RINm5F). Special attention was paid to the role of polyamines for these processes, since these compounds have been implicated in the regulation of growth and function of insulin-producing cells. For this purpose RINm5F cells were maintained in culture for 4 days in the presence or absence of 1-2 mM sodium butyrate. It was found that sodium butyrate dose-dependently inhibited the proliferative activity of the RINm5F cells along with a decreased cellular polyamine content. The cellular content of insulin and secretion of the hormone into the culture medium were, however, not altered by sodium butyrate treatment, and neither did this treatment impose a glucose-sensitive insulin release. The decreased polyamine content was restored by the concomitant addition of exogenous putrescine; however, despite this, the reduced cell proliferation persisted. From these findings we conclude that the decreased growth rate evoked by sodium butyrate results from other events than specific polyamine synthesis inhibition. It is furthermore demonstrated that the processes of cell proliferation and regulation of cellular insulin content and secretion can be dissociated in the RINm5F cell line. PMID- 8490205 TI - Antiproliferative and chemomodulatory effects of interferon-gamma on doxorubicin sensitive and -resistant tumor cell lines. AB - Biological agents might offer various therapeutic opportunities in the treatment of cancer, including a direct and/or host-mediated antiproliferative effect and also the possibility to favorably modulate tumor resistance to antineoplastic drugs. We studied the in vitro antiproliferative effects of interferon (IFN) gamma on the mouse B16 melanoma and Friend erythroleukemia, and the human K562 erythroleukemia, as doxorubicin (DXR)-sensitive and -resistant (multidrug resistant) variants. These effects were marked in B16 melanoma and rather slight in K562 erythroleukemia, without any difference between the DXR-sensitive and resistant lines. The chemosensitive variant of Friend erythroleukemia showed an intermediate response, which was greater than that seen in its resistant counterpart. There was no apparent relationship between the antiproliferative activity of IFN-gamma and the glutathione content of the cell lines. On the other hand, this activity was enhanced by co-treatment with glutathione-depleting concentrations of buthionine sulfoximine, but only in the cell lines which had responded better to IFN-gamma alone. This result probably confirms that a free radical mechanism plays a part in the antitumor effect of the cytokine. Finally, a range of concentrations of IFN-gamma, including slightly cytotoxic ones, did not substantially improve the antiproliferative effects of doxorubicin on the various cell lines, except in the DXR-sensitive variant of Friend erythroleukemia where a synergistic effect of the combination was observed. Thus, our results are not very promising with regard to a possible favorable modulatory activity by IFN gamma of DXR (multidrug)-resistance. PMID- 8490206 TI - Isothiocyanates inhibit cell cycle progression of HeLa cells at G2/M phase. AB - To analyze the inhibitory effects of isothiocyanates on the growth of human cancer cells, the effects of these compounds on the cell cycle progression of HeLa cells were studied by flow cytometry. The accumulation of cells at G2/M phase was observed at 16 h after treatment with 10 microM allyl isothiocyanate, 2.5 microM benzyl or phenethyl isothiocyanate, at which concentrations the cell growth was inhibited to 41-79% of control. These results suggest that isothiocyanates delay the cell cycle progression of HeLa cells, leading to inhibition of cell growth. PMID- 8490207 TI - Serotonin and the mammalian circadian system: I. In vitro phase shifts by serotonergic agonists and antagonists. AB - The primary mammalian circadian clock, located in the suprachiasmatic nuclei (SCN), receives a major input from the raphe nuclei. The role of this input is largely unknown, and is the focus of this research. The SCN clock survives in vitro, where it produces a 24-hr rhythm in spontaneous neuronal activity that is sustained for at least three cycles. The sensitivity of the SCN clock to drugs can therefore be tested in vitro by determining whether various compounds alter the phase of this rhythm. We have previously shown that the nonspecific serotonin (5-HT) agonist quipazine resets the SCN clock in vitro, inducing phase advances in the daytime and phase delays at night. These results suggest that the 5-HT ergic input from the raphe nuclei can modulate the phase of the SCN circadian clock. In this study we began by using autoradiography to determine that the SCN contain abundant 5-HT1A and 5-HT1B receptors, very few 5-HT1C and 5-HT2 receptors, and no 5-HT3 receptors. Next we investigated the ability of 5-HT-ergic agonists and antagonists to reset the clock in vitro, in order to determine what type or types of 5-HT receptor(s) are functionally linked to the SCN clock. We began by providing further evidence of 5-HT-ergic effects in the SCN. We found that 5-HT mimicked the effects of quipazine, whereas the nonspecific 5-HT antagonist metergoline blocked these effects, in both the day and night. Next we found that the 5-HT1A agonist 8-OH-DPAT, and to a lesser extent the 5-HT1A-1B agonist RU 24969, mimicked the effects of quipazine during the subjective daytime, whereas the 5-HT1A antagonist NAN-190 blocked quipazine's effects. None of the other specific agonists or antagonists we tried induced similar effects. This suggests that quipazine acts on 5-HT1A receptors in the daytime to advance the SCN clock. None of the specific agents we tried were able either to mimic or to block the actions of 5-HT or quipazine at circadian time 15. Thus, we were unable to determine the type of 5-HT receptor involved in nighttime phase delays by quipazine or 5-HT. However, since the dose-response curves for quipazine during the day and night are virtually identical, we hypothesize that the nighttime 5-HT receptor is a 5-HT1-like receptor. PMID- 8490208 TI - Serotonin and the mammalian circadian system: II. Phase-shifting rat behavioral rhythms with serotonergic agonists. AB - The suprachiasmatic nuclei (SCN) receive primary afferents from the median and dorsal raphe, but the role of these projections in circadian timekeeping is poorly understood. Studies of the SCN in vitro suggest that quipazine, a general serotonin (5-HT) receptor agonist, can produce circadian time-dependent phase advances and phase delays in circadian rhythms of neuronal activity. The present study addresses whether quipazine and the selective 5-HT1A receptor agonist 8-OH DPAT are similarly effective in vivo. Drinking and wheel-running patterns of male Wistar rats individually housed in constant darkness were monitored before and after subcutaneous administration of quipazine (5-10 mg/kg) at either circadian time (CT) 6 or CT 18, with and without running wheels available. Dose-dependent phase advances (20-180 min) were produced at CT 6. Significant phase shifts were not observed at CT 18. CT 6 quipazine-treated animals also showed a sustained and significant shortening of rhythm period (tau) following treatment (-0.28 hr; p < 0.002). tau shortening was inconsistently observed in CT 18 quipazine-treated rats. Neither quipazine-induced phase shifts nor tau effects were dependent on wheel-running activity per se. 8-OH-DPAT delivered via intracerebral ventricular treatment into the third ventricle (5 microliters at 100 microM in saline) produced slightly smaller phase advances (20-90 min) at CT 6, but did not produce phase delays at CT 18 or changes in tau. These findings support in vitro evidence that 5-HT-ergic agonists can phase-shift the circadian pacemaker. PMID- 8490209 TI - On the relationship between motor activity and the sleep-wake cycle in humans during temporal isolation. AB - In the free-running circadian rhythms of 14 human subjects (4 females, 10 males) who lived singly in an isolation unit without temporal clues, locomotor activity was recorded by means of contact plates installed below the carpet in the main room. During sleep, movements in bed were picked up by spring contacts attached to the mattress. In all subjects, the hourly means of locomotion during wakefulness (alpha) were negatively correlated with the duration of alpha to such an extent that the total amount of locomotion per cycle remained constant when alpha varied from 14 to 23 hr. The hourly values of movements in bed were independent of the duration of sleep (rho), so that the total number of movements was almost proportional to rho. The "homeostatic control" of locomotion during wake time is considered as a means to conserve energy when the duration of wakefulness increases. PMID- 8490210 TI - Photoperiodic time measurement and a graded response in a cockroach. AB - Almost exclusively, photoperiodic insects respond to a given photoperiod in one of two ways: a "long-day" response or a "short-day" response. Intermediate responses occur only at a very restricted range of photoperiods (often less than 30 min) and are generally population phenomena rather than intermediate responses of individuals. In contrast, individuals of the wood roach, Parcoblatta pennsylvanica, show intermediate responses over a broad range of photoperiods. We examined the effect of constant light, constant darkness, and photoperiods ranging from 10 to 18 hr of light per 24 hr on growth rate as measured by weight gain, and found a robust photoperiodic response. Nymphs raised in photoperiods with light periods (photophases) from 0 to 12 hr gained little weight, whereas those in LD 18:6 were almost 15 times heavier. This is the first report of a photoperiodic response curve for a cockroach. Interestingly, there was a linear relationship between the duration of the photophase and weight gain over a broad range of photoperiods (LD 12:12 to LD 18:6; r2 = 0.99). Statistical analysis showed that the intermediate responses were attributable to individuals' growing at an intermediate rate. Another interesting observation was that all larval stages appeared to be capable of perceiving and responding to photoperiodic signals. The results of further experiments using non-24-hr photoperiods were consistent with the existence of a circadian component in the photoperiodic time measurement in this species. PMID- 8490211 TI - Behavioral decoupling of circadian rhythms. AB - Golden hamsters (Mesocricetus auratus) were kept in a light-dark cycle (LD 14:10). For 2 weeks, almost every day they were placed in a novel running wheel for 3 hr, starting 7 hr before dark onset. Most of the animals made several thousand wheel revolutions during this 3 hr. When these animals were subsequently transferred to a dark room, their activity was split into two components, one close to the time of the previous exposure to the novel wheel and the other close to the time when they had been active in the dark phase of the previous LD cycle. The two components fused after a few days in darkness. These observations show that nonphotic events are capable of causing major reorganizations of circadian activity patterns, despite the presence of an LD cycle. PMID- 8490212 TI - Behavior in light-dark cycles of Drosophila mutants that are arrhythmic, blind, or both. AB - Certain of the rhythm mutations in Drosophila melanogaster lead to arrhythmic locomotor activity (and aperiodic eclosion) in constant conditions. In light-dark (LD) cycles, however, such mutants exhibit clear fluctuations between high levels of activity when the lights are on and much lower ones when they are off. Our data, in contrast to some previous conclusions, strongly suggest that period0 (per0) adults are, in LD conditions, merely being "forced" into exhibiting periodic behavior. These experiments involved application of 8-, 12-, 16-, and 24 hr LD cycles, in which the arrhythmic mutant could have any of these periodicities imposed upon it, whereas wild-type flies tended to exhibit periods of about 24 hr in cycling conditions whose T values were > 8 hr different from 24. In phase-shift experiments, it was found that Drosophila expressing genotypes associated with rhythmicity achieved a 5-hr advance over a 2-day period following an advanced lights-on; per0 adults altered the phase of their locomotor peaks more rapidly. Against a background of the fact that eyeless or blind flies exhibit normal entrainment, it was hypothesized that double-mutant flies- carrying such visual mutations and per0 as well--should not synchronize to LD cycles, if the forced rhythms seen in the latter single-mutant type are mediated solely by light input through the external photoreceptors. Since an appreciable proportion of the double mutants did synchronize (to LD 12:12), it is thus suggested that the visual cues involved in forcing rhythmicity could be input through the same extraocular photoreceptors that, in general, subserve the fly's rhythm system. PMID- 8490213 TI - Being a burden on others. PMID- 8490215 TI - Do physicians' own preferences for life-sustaining treatment influence their perceptions of patients' preferences? PMID- 8490214 TI - The problem of proxies with interests of their own: toward a better theory of proxy decisions. PMID- 8490216 TI - The vagaries of patients' and families' discussing advance directives. PMID- 8490217 TI - Insights pertaining to patient assessments of states worse than death. PMID- 8490218 TI - Analyzing the values history: an evaluation of patient medical values and advance directives. PMID- 8490219 TI - Is the Patient Self-Determination Act appropriate for elderly persons hospitalized for depression? PMID- 8490220 TI - Establishing advance medical directives with demented patients: a pilot study. PMID- 8490221 TI - Decision making in an incapacitated patient. PMID- 8490222 TI - Authenticity, autonomy, and mental disorders. PMID- 8490223 TI - Meaning what you say. PMID- 8490224 TI - Patients should not always come first in treatment decisions. PMID- 8490225 TI - Hardwig on proxy decision making. PMID- 8490226 TI - Justice within intimate spheres. PMID- 8490227 TI - From PSDA to PTSD: the Patient Self-Determination Act and post-traumatic stress disorder. PMID- 8490228 TI - The PSDA and the depressed elderly: "intermittent competency" revisited. PMID- 8490229 TI - Advance directives: what have we learned so far? AB - As a result of the recent intense focus on advance directives, it is now possible to resolve several questions. It is clear that instructional directives are best able to represent a patient's wishes in the clinical context if they make use of scenario- and treatment-specific statements, perhaps combined with other types of value statements. Instructional directives are a type of advisory document that can provide clear and convincing evidence regarding a patient's wishes and, as such, the patient's wishes can thereby be constitutionally protected. It is clear that proxy judgments that are not specifically informed are not a good match with patients' wishes. Proxy decisions should, therefore, be guided by instructional directives--verbal or documented. It is now possible to construct a good clinical process for advance planning that is practical, maximizes benefits and minimizes risks, and includes both instructional planning and proxy empowerment. However, we have a long way to go before advance planning is widely and appropriately practiced. PMID- 8490230 TI - The PSDA and geriatric psychiatry: a cautionary tale. PMID- 8490231 TI - Application of cryotechniques in cartilage tissue preservation and immunoelectron microscopy: potentials and problems. AB - Cryotechnical processing of cartilage has the potential to solve many of the tissue-specific problems associated with various routine chemical fixation protocols. This is particularly the case with respect to extracellular matrix architecture, the distortion or destruction of which (caused by extraction and/or precipitation of proteoglycan molecules) may be prevented. Adoption of such techniques also permits high-sensitivity immunoelectron-microscopy of the extracellular matrix space (carbohydrate epitopes). However, a number of difficulties still remain to be resolved, particularly that of matrix-cell interface separation occurring during freeze substitution and low temperature embedding. These problems are briefly addressed and possible solutions outlined. PMID- 8490232 TI - Improved preservation of ultrastructure in difficult-to-fix organisms by high pressure freezing and freeze substitution: I. Drosophila melanogaster and Strongylocentrotus purpuratus embryos. AB - In this study, we have applied the techniques of high pressure freezing and freeze substitution to embryonic cell types which are usually difficult to fix properly for electron microscopy. In both Drosophila and Strongylocentrotus purpuratus, we see improved preservation of both membrane systems and cytoskeleton when compared to published results on the same cells using conventional electron microscope (EM) fixation methods. Finally, we have seen that postembedding labelling of sections is possible even after light osmium fixation during freeze substitution. PMID- 8490233 TI - Freeze substitution after fast-freeze fixation in preparation for immunocytochemistry. AB - As compared to classical chemical fixation, the physical immobilization of ultrastructures by fast-freeze fixation (FFF) and the subsequent exchange of water in its solid state by freeze substitution (FS) improve the preparation procedure for immunogold labeling (IGL). FFF-FS results in a morphological preservation of unchallenged quality, as well as in a better preservation of antigenic reactivity, thus allowing remarkable precision of labeling on sections. However, FFF, particularly over a cooled metal plate, requires a heavy and expensive machine. It is not suitable for all biological specimens and in the best conditions, which remain difficult to standardize, the thickness of the well preserved portion of the specimen does not exceed a few microns for compact tissues, and exceptionally 30-40 microns for isolated cells. The FS procedure is long and must be adjusted empirically for every new specimen and antigenic detection. The preservation of a given antigen's reactivity in the presence of fixative agents and embedding resins remains unpredictable. The action of fixative agents is different and milder in FS than when they are used classically in chemical fixation. By chance, one of the best FS procedures for the preservation of both ultrastructure and antigenicity appears to be by using acetone alone, together with a molecular sieve to improve the water exchange process. A large choice of embedding resins usually allows us to find a compromise between ultrastructural and antigenic preservation. PMID- 8490234 TI - Freeze-substitution for morphological and immunocytochemical studies in insects. AB - Methods of plunge freezing and freeze-substitution (FS) for insect antennae and similar body appendages are described. In these more or less cylindrical specimens, usually a layer below the cuticular surface of 10-15 microns thickness is well preserved without freezing damage, further inwards ice-crystal ghosts of increasing size are encountered, but in the very centre of antennal branches (diameter approximately 80 microns) of the silkmoth, Bombyx mori, freezing damage is usually reduced again. The frost-hardy species, Poecilocampa populi and Boreus hiemalis, exhibit regions free from freezing damage up to 40 microns below the cuticular surface. Secondary freezing damage in silkmoth sensory hairs is observed only after deliberately warming the specimens to -43 degrees C for >> 10 min before FS. Secondary artefacts due to the substitution process are investigated by comparison with freeze-etching and by comparing different FS media and protocols. Methanol is not recommended as a substitution medium for insect specimens. Structures particularly liable to substitution damage are the stimulus-conducting pore tubules of olfactory sensilla and the receptor cell membrane. Extraction of soluble components is more likely with pure organic solvents without added chemical fixing agents and with prolonged substitution at elevated temperatures. Such extraction may also be a possible artefact with soluble antigens in immunocytochemical studies. A review is given of the major achievements attained with these techniques is insect functional morphology and immunocytochemistry. PMID- 8490236 TI - Discrepancies in kinematic calculations of HOLZ lines. AB - We have found significant differences between the results of computer simulations of HOLZ line patterns. The computations in question are made in the kinematical approximation. After trivial errors are eliminated the programs fall into two groups. There is a discrepancy between the two that increases with distance from the zone axis. The difference is small but not negligible at the level of precision used in determining lattice parameters or strain. We show which of the two is correct in the kinematic approximation and that the discrepancy between the two groups is of the order of the error introduced by dynamical interaction. PMID- 8490235 TI - Cross-sectional AEM preparation technique for ceramic-coated WC-Co cutting tools. AB - The preparation of cross-sectional specimens for AEM studies of materials such as ceramic coated tungsten carbide presents some unique problems. Pieces joined by the use of epoxides often separate at the interface between the WC and ceramic coating during the initial mechanical grinding and subsequent thinning process as a result of the vibration and physical strain placed on the sample. These problems have been overcome through the use of a preparation process which essentially encapsulates the sample within the confines of an epoxy filled quartz tube. This preparation process has allowed for facile AEM cross-sectional analysis of TiN/TiCN coatings on WC-Co substrates, and has revealed two distinct grain morphologies within the TiCN coating. PMID- 8490237 TI - Rapid fixation and embedding method for immunocytochemical studies of tomato spotted wilt tospovirus (TSWV) in plant and insect tissues. AB - A new rapid fixation and embedding technique using microwave energy was evaluated for immunolabelling and examination of ultrastructure of plant and insect cells. Tissues in gluteraldehyde-paraformaldehyde were fixed for fifteen seconds in a microwave at 100% power, and dehydrated. Microwave energy was then used to polymerize the London Resin White (LR White) acrylic resin during the embedding process. Embedded specimens were then thin sectioned (90 nm) and treated with anti-tomato spotted wilt tospovirus (TSWV) antiserum followed by protein A-gold label, or antisera against a TSWV encoded nonstructural protein followed by goat anti-rabbit gold label. Using this technique, structural and nonstructural proteins of TSWV were readily detected and specifically labelled in cells of the insect vector, the western flower thrips, Frankliniella occidentalis (Pergande), and in infected cells of the plant species, Emilia sonchifolia L. PMID- 8490238 TI - Rapid freezing replica studies of membrane specializations in the proximal tubules of mouse kidney. AB - The membrane specializations of the fresh unfixed kidney cortex of adult and neonatal ICR mice were examined by using rapid freezing replica methods. In proximal tubular cells, numerous apical intracellular tubules exhibited helical patterns on the E face with a pitch of about 12 nm. This regular pattern was often continuous with similar striped indentations on the edge of the vacuoles connecting with the tubules. On the luminal surface (ES) of these vacuoles, membrane surface particles were arranged regularly in striped patterns with a center-to-center spacing of about 12 nm. We could not identify differentiations on the PF or PS of the same membrane systems. Another membrane specialization was a plaque or patch of clear pits in tilted lattice alignments on the P face of the large vacuoles with a center-to-center spacing of about 20 nm. This type of specialization was often observed in the neonatal mice proximal tubular cells. These membrane specializations may indicate the active membrane functions in the proximal tubules and suggest the functional continuity and structural relationship of these apical endocytic membrane systems. PMID- 8490239 TI - Quantitative analysis and cartography in scanning electron microscopy: application to the study of bacterial adhesion to respiratory epithelium. AB - This paper describes the coupling between a scanning electron microscope (SEM) and an image analysis workstation. The system was designed in order to drive the SEM and to analyse any sample. It allows automatic (edge detection) or semiautomatic (pointing, marking, drawing) object detection. Two types of data can be obtained: (1) topographical information, such as the location of the object within a region of interest drawn at any magnification of the microscope, or (2) quantitative data, such as morphometric characteristics of objects. In addition, high resolution maps of the section, regions of interest, and objects can be obtained with a laser printer. This software was first applied to quantitate the adhesion of the bacteria Pseudomonas aeruginosa to human respiratory epithelial cells in culture. P. aeruginosa was shown associated with ciliated cells. The second application concerned the study of the distribution of specific carbohydrate residues at the surface of the respiratory cells. The gal residues were revealed using the lectin Ricinus communis agglutinin II, adsorbed to colloidal gold particles. A relationship between the presence of adherent bacteria and labelling was shown. PMID- 8490240 TI - Differential distribution of major gangliosides in rat central nervous system detected by specific monoclonal antibodies. AB - We investigated the localization of major gangliosides in adult rat brain by an immunofluorescence technique with mouse monoclonal antibodies (MAbs). Five MAbs (GMB16, GMR17, GGR12, GMR5 and GMR13) that specifically recognize gangliosides GM1, GD1a, GD1b, GT1b and GQ1b, respectively, were used. We have found that there is a cell type-specific expression of the ganglioside in the rat central nervous system. In cerebellar cortex, GM1 was expressed in myelin and some glial cells. GD1a was detected exclusively in the molecular layer. GD1b and GQ1b were present restrictedly on the granular layer; GD1b was detected on the surface of the granular cell bodies, whereas GQ1b was present in the cerebellar glomerulus. GT1b was distributed intensely in both the molecular layer and the granular layer. In cerebral cortex, GM1 was detected in some glial cells. Dense staining was limited to the white matter. GD1a was distributed in layers I, II/III and Va, and the upper part of layer VI, whereas GQ1b was localized in layers IV and Vb, and the lower part of layer VI. GD1b was detected beneath layer III. GT1b appeared to be distributed throughout all layers. In other regions, such as hippocampal formation and spinal cord, the expression of the ganglioside was also highly localized to a specific cell type and layer. PMID- 8490241 TI - Purification and characterization of bovine mannan-binding protein. AB - Bovine mannan-binding protein (bMBP) was observed in serum by its Ca(2+) dependent binding to mannan and by an M(r) of 28 kDa under reducing conditions on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The lectin was isolated by precipitation with polyethyleneglycol (PEG), affinity chromatography on mannan-Sepharose eluted with EDTA, and absorption on Sepharose 4B rabbit anti-bovine Ig to remove anti-mannan antibodies. Fractions containing the lectin were reapplied to mannan-Sepharose and eluted first with N-acetyl-D glucosamine (GlcNAc) to remove conglutinin, and then with mannose to elute the 28 kDa lectin. Further purification was achieved by ion-exchange chromatography on Mono-Q and by mannose-gradient elution from a mannan-Sepharose column. SDS-PAGE of the purified lectin showed three high molecular weight bands under non reducing conditions. The reduced protein gave a single band of 28 kDa. On gel permeation chromatography under non-dissociating conditions, the protein emerged at a volume corresponding to M(r) approximately 750 kDa. Amino acid analysis showed the presence of hydroxyproline and hydroxylysine, and a high glycine content (17.7%), suggesting the presence of a collagen-like structure. This was supported by the susceptibility of the protein to collagenase digestion. The N terminal 26 amino acids showed 62% identity with human MBP, when three gaps were allowed in the alignment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490242 TI - Effects of overexpression of beta 1,4-galactosyltransferase on glycoprotein biosynthesis in F9 embryonal carcinoma cells. AB - beta 1,4-Galactosyltransferase (GalTase) plays a central role in the biosynthesis of N-acetyllactosamine-containing oligosaccharides. However, despite this seemingly important function, little is known about how changes in the levels of GalTase affect oligosaccharide biosynthesis. We have examined the effects of overexpressing GalTase on the glycosylation of endogenous glycoproteins in F9 mouse embryonal carcinoma cells. Cells transfected with either the short form of the GalTase cDNA (encoding a protein of 386 amino acids) or the long form of the GalTase cDNA (encoding a protein of 399 amino acids) had a 3-fold increase in total GalTase activity, relative to control F9 cells. Analysis of pronase digested glycopeptides obtained from control and transfected cells after metabolic labelling with [6-3H]galactose revealed no significant qualitative or quantitative differences, as assessed by Bio-Gel P-6 gel filtration chromatography and Tomato lectin affinity chromatography. Furthermore, SDS-PAGE analysis of immunoprecipitated [3H]galactose-labelled lysosomal-associated membrane protein-1 (LAMP-1) glycoprotein showed no difference in amounts or mobility. Pronase digestion and subsequent analysis of the gel-fractionated LAMP 1 glycoproteins also indicated no differences between the various cell lines. The inability of elevated GalTase activity to affect glycosylation was not due to limiting levels of GalTase substrates, since an excess of substrates was detectable in lysed cells using either endogenous or exogenous GalTase and UDP [3H]galactose. Finally, the subcellular distribution of GalTase, as assessed by sucrose gradient fractionation, was similar between all cell types, thus suggesting that GalTase was appropriately compartmentalized in the transfected cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490243 TI - Cell differentiation in Dictyostelium discoideum controls assembly of protein linked glycans. AB - The prestalk and prespore cells from the Dictyostelium discoideum multicellular slug stage of development differ in assembly of glycoconjugates. Prespore cells are 2- to 3-fold more active than prestalk cells in the assembly of N-linked glycans and 20-fold more active in their fucosylation. Only prespore cells synthesize an O-linked glycan consisting in part of Fuc alpha-linked to N acetylglucosamine. Incorporation of fucose, glucosamine, mannose and galactose into large pronase-resistant glycoconjugates was almost exclusively into prespore cells. Such glucosamine-labelled glycoconjugates resist fragmentation by beta elimination and include a glycoantigen dependent on the modB genetic locus. In contrast, large fucose-labelled glycoconjugates consisted of multiple, small, O linked oligosaccharides on carrier peptides. The spore coat protein SP96 has several fucosylated O-linked oligosaccharides, one of which correlates with a fucose epitope previously shown to localize in prespore vesicles and the outer layer of the spore coat. PMID- 8490244 TI - Expression and characterization of a carbohydrate-binding fragment of rat aggrecan. AB - The COOH-terminal portion of cartilage proteoglycan core protein, aggrecan, expressed by in vitro translation, binds carbohydrate-containing affinity columns. The in vitro expression approach has been used to define the sugar binding portion of the core protein. The active fragment, which corresponds closely to the carbohydrate-recognition domains in the family of Ca(2+)-dependent (C-type) animal lectins, has been expressed in bacteria and characterized. The CD spectrum of the domain is very similar to the spectrum of the binding domain of serum mannose-binding protein, suggesting that its overall structure probably resembles the known three-dimensional structure of the mannose-binding domain. The binding specificity of the core protein fragment has been characterized using a solid-phase assay. The results suggest that the monosaccharide-binding site is also similar to that in other C-type carbohydrate-recognition domains. PMID- 8490245 TI - Core 2 GlcNAc-transferase and polylactosamine expression in O-glycans. PMID- 8490246 TI - Biological roles of oligosaccharides: all of the theories are correct. AB - Many different theories have been advanced concerning the biological roles of the oligosaccharide units of individual classes of glycoconjugates. Analysis of the evidence indicates that while all of these theories are correct, exceptions to each can also be found. The biological roles of oligosaccharides appear to span the spectrum from those that are trivial, to those that are crucial for the development, growth, function or survival of an organism. Some general principles emerge. First, it is difficult to predict a priori the functions a given oligosaccharide on a given glycoconjugate might be mediating, or their relative importance to the organism. Second, the same oligosaccharide sequence may mediate different functions at different locations within the same organism, or at different times in its ontogeny or life cycle. Third, the more specific and crucial biological roles of oligosaccharides are often mediated by unusual oligosaccharide sequences, unusual presentations of common terminal sequences, or by further modifications of the sugars themselves. However, such oligosaccharide sequences are also more likely to be targets for recognition by pathogenic toxins and microorganisms. As such, they are subject to more intra- and inter-species variation because of ongoing host-pathogen interactions during evolution. In the final analysis, the only common features of the varied functions of oligosaccharides are that they either mediate 'specific recognition' events or that they provide 'modulation' of biological processes. In so doing, they generate much of the functional diversity required for the development and differentiation of complex organisms, and for their interactions with other organisms in the environment. PMID- 8490247 TI - Combined TEM and SEM analysis of the rostral wall of the human III ventricle. AB - A combined morphological study using transmission and scanning electron microscopy was carried out on the central zone of the rostral wall of the III ventricle from a sample taken during the operation of a patient with a retrochiasmatic craniopharyngioma. Under the scanning electron microscope, the apical cell wall of the ependymocytes generally appeared folded and lack in cilia, but with numerous microvilli developed to different extents. The flat surface cells were scarce and were polygonal in shape and limited by 3-7 prominent edges. Ultrastructural analysis revealed the existence of several types of ependymocytes and subependymal epithelial cells arranged in different layers; in both layers the presence of abundant neurofilaments and intercellular junctions was striking. PMID- 8490248 TI - Pinocytotic vacuoles in human dental pulp capillaries. AB - Dental pulp capillaries were studied in human. They were of the continuous type, with the exception of a small number which were of the fenestrated type, located in the vicinity of the odontoblasts. A characteristic morphological peculiarity was found in the endothelial cells. In places there was a large quantity of multi sized vacuoles. The vacuoles were evidently of pinocytotic origin, and their content was emptied into the extracapillary space. The initiation of their formation was indicated by the creation of cytoplasmic flaps, which could not be characterised as typical pseudopodia, and which in cross sections resembled microvilli. The flaps engulfed a quantity of plasma and then, after bending over, their edge fused with the cell, creating a vacuole. The vacuole, after being moved abluminally, was emptied into the pericapillary area by exocytosis. There was indication that flaps created at the borders of the endothelial cells (flanges) acted likewise, transporting vacuoles through the intercellular spaces. Micropinocytosis, was a distinctly different phenomenon, contributing, to a very small degree, to the intracellular enlargement of the vacuoles. It seems that this vacuolar mechanism of transportation serves an augmented metabolic need of the surrounding tissue. PMID- 8490249 TI - A quantitative description of the insulin-induced ultrastructural changes in newborn rat hepatocytes. AB - The effects of insulin on the ultrastructure of newborn rat hepatocytes were systematically quantified at satisfactory statistical significance. Insulin prevented the normal postnatal increase in the total volume of lysosomes and the breakdown of glycogen inside these organelles. The lysosomal glycogen-hydrolysing enzyme, acid alpha 1,4 glucosidase was inhibited by the hormone. Insulin also prevented the normal postnatal increase in the total volume of peroxisomes, especially of the crystalloid core-devoid type. The hormone produced an increase in the area of cell membrane, due to the formation of many irregular folds of the cell surface. These results constitute good evidence for participation of lysosomes and peroxisomes in the overall glycogen degradation and or gluconeogenesis in the newborn rat hepatocytes. PMID- 8490250 TI - Gastric intestinal metaplasia eleven years after randomized selective proximal vagotomy for peptic ulcer. AB - The presence of intestinal metaplasia (IM) 11 years after selective proximal vagotomy (SPV), selective proximal vagotomy with pyloroplasty (SPV + PP) and selective vagotomy with pyloroplasty (SV + PP) was investigated in 38 consecutive patients. IM was significantly more frequent in SPV than in SV + PP, SPV + PP or in unoperated controls of matching ages. IM occurred more frequently both at an older age (> or = 60 years) in SPV and in a larger number of gastric areas than in the other group of patients. Reports in the literature indicate that vagotomy may increase the risk of gastric carcinoma and that IM may antedate malignant transformation. It would thus appear that patients previously operated with SPV (without pyloroplasty) having IM, should be the group of patients to be enrolled in endoscopical surveillance programs for detection of possible cancer development. PMID- 8490251 TI - Pathological changes in organs of rats chronically exposed to hypoxia. Development of pulmonary lipidosis. AB - Rats were exposed to chronic normobaric hypoxia of progressively increasing severity; down to 8% or 7% oxygen concentrations. In addition to loss of weight, pathology revealed congestion, haemorrhages, hypertrophy of the heart involving mainly the right ventricle, thickening of arteries, ischaemic changes in the myocardium and extramedullary haematopoiesis in the spleen. Changes not described up until now were: 1) sheets of foam cells in the pulmonary alveoli; 2) foamy and solid storing cells in the spleen; 3) mucoid changes in the atrioventricular valve leaflets; 4) hyperplasia of the juxtaglomerular apparatus; 5) atrophy of the adrenal glomerulosa and hyperplasia of medulla; 6) atrophy of the perifollicular B-cell zone in the spleen; and 7) lipid pigment deposition in various organs. The findings indicate that severe chronic hypoxia induces a significant pulmonary lipidosis similar to that caused by amphiphilic cationic drugs, presumably by inhibiting hydrolytic enzyme activities. The observations are of importance in human hypoxic conditions and open the possibility of their rational treatment. PMID- 8490252 TI - Fine structure of the retinal epithelium of the tiger salamander (Ambystoma tigrinum). AB - The retinal pigment epithelium (RPE) of the tiger salamander (Ambystoma tigrinum) consists of a single layer of large squamous-shaped cells. These RPE cells are but minimally infolded basally (sclerally) but show numerous apical (vitreal) processes that interdigitate with the photoreceptor cells. A series of apically located tight junctions joins the RPE cells to form part of the blood-ocular barrier. Internally the RPE nucleus is large, vesicular and flattened. Smooth endoplasmic reticulum predominates in these cells with only occasional small profiles of rough endoplasmic reticulum present. Polysomes and basally-located mitochondria are plentiful. Golgi zones, lipid droplets, lysosome-like bodies and phagosomes of outer segment material are also present. Myeloid bodies which may show ribosomes on their surface are also numerous. The round to oval melanosomes undergo retinomotor movements and in the light-adapted state reach almost to the external limiting membrane. Bruch's membrane or complexus basalis shows a pentalaminate structure with the central elastic lamina poorly represented. The choriocapillaris is a single layer of large anastomosing capillaries which are but minimally fenestrated. PMID- 8490253 TI - Fine structure of the retinal photoreceptors of the tiger salamander (Ambystoma tigrinum). AB - The retinal photoreceptors of the tiger salamander (Ambystoma tigrinum) have been studied by light and electron microscopy in both light- and dark-adaptation. Rods and cones are present in this duplex retina in a ratio of about 20:1. As in other urodele species these photoreceptors are very large cells. The rod outer segment is composed of bi-membranous discs of uniform diameter displaying several very deep incisures. The rod inner segment displays an ellipsoid of mitochondria and a myoid region which changes in diameter during the lighting cycle indicating that rods undergo photomechanical movements. Rod nuclei are located at all levels of the outer nuclear layer and rod spherules are large and display several invaginated and superficial synaptic sites. Cone photoreceptors while large cells are smaller than the rods. They show a smaller tapering outer segment, a large distal ellipsoid of mitochondria and a prominent paraboloid of glycogen but no oil droplet within the inner segment. Judging by the width of the myoid region which remains similar throughout the lighting cycle, cones in this species show no retino-motor responses. Cone nuclei are less electron dense than rods and are also located at all levels of the outer nuclear layer. The cone synaptic pedicle is larger than that of the rods and also shows several invaginated and superficial synaptic sites. PMID- 8490254 TI - Lectin histochemical study on the kidney of normal and streptozotocin-induced diabetic hamsters. AB - Lectin histochemical characteristics of the kidney of normal and streptozotocin (SZ)-induced diabetic APA hamsters were investigated. Paraffin sections of the kidney of animals killed at 1 and 3 months after SZ-injection were stained with the following 10 lectins: PNA, BPA, DBA, SBA, GSA-I, GSA-II, MPA, WGA, UEA-1 and Con A. Renal lectin binding characteristics of normal APA hamsters differed in some aspects from those in other species reported previously. In the kidney of SZ induced diabetic APA hamsters, binding activities of some lectins increased in the affected Bowman's capsules and glomeruli as well as in degenerated epithelial cells of uriniferous tubules. Among them, GSA-II in particular exhibited strong binding activity to the degenerated epithelial cells of Bowman's capsules, distal convoluted tubules and collecting ducts. PMID- 8490255 TI - Histochemical localization of glycosaminoglycans in the omasal papillae of sheep. AB - Histochemical localization of the glycosaminoglycans in the omasal laminae were examined at light and electron microscopic levels. The core region of the omasal papillae was stained strongly with alcian blue at pH 2.5 and 1.0. The staining was degraded moderately and completely when tissue sections were pretreated with mild and active methylation, respectively. Alcianophilia was moderately decreased with saponification. Furthermore, enzymatic digestion procedures showed that these alcianophilic substances contained a large amount of hyaluronic acid and chondroitin sulphate. Ultrastructurally, a spider web-like structure was widely distributed among the spindle-shaped fibroblast-like cells and fibrous networks of collagen and elastin. These results suggest that the core region of the omasal papillae not only acts as a physical buffer resisting the local pressure from the lumen, but may also influence material transport through the omasal mucosa. PMID- 8490256 TI - Effects of chronic ethanol administration on the serotonin-producing cells in rat gastric antral and duodenal mucosa. AB - The present study describes our observations on optical and ultrastructural features of serotonin-containing cells in the rat antral and upper duodenal mucosa, utilizing optic morphometric measurements in a model of experimental chronic alcoholism of rat in which nutrition was well controlled. Male Wistar rats were given ethanol to provide 23 per cent of the total calories, while starch replaced ethanol isocalorically in controls. Twenty-five per cent of the calories were provided by protein in both groups. Blood levels of serotonin were significantly raised after chronic ethanol feeding (0.059 +/- 0.06 vs. 0.159 +/- 0.012 micrograms/ml, p < 0.01). Decrease in the number of immunohistochemically detectable serotonin-containing cells was found in the pyloric gland mucosal area specimens of the chronically ethanol-treated rats (68.9 +/- 5.2 vs 43.3 +/- 3.0; p < 0.001). The immunohistologically-evaluated number of the same cells in the duodenal mucosa specimens was significantly decreased by alcohol feeding. Although total villi and crypt count per whole circular section, and the number of crypts per villus were not significantly changed either in control animals or in chronically ethanol-fed rats, decreased number of these cells per whole circular section (289 +/- 21.6 vs. 183 +/- 10.5; p < 0.001) per villus (2.52 +/- 0.14 vs. 1.21 +/- 0.10; p < 0.001) and per crypts (0.97 +/- 0.08 vs. 0.79 +/- 0.04; p < 0.05) were reported after alcohol consumption. In both control and experimental rats the cells were predominantly found in the basal half of the antropyloric mucosa. Alcohol did not lead to any changes in normal distribution of the duodenal serotonin-producing cells. The above quantitative changes in serotonin-producing cells were not accompanied by changes in their subcellular appearance in stomach and duodenal mucosa of alcohol-treated rat. PMID- 8490257 TI - Morphological changes induced by colchicine in the chick optic cup in early stages of development. A stereological study. AB - In this study chick embryo optic cups at HH stage 13 of development were analyzed under normal conditions and after inoculation with colchicine for 1, 2, 4, and 8 h. Several changes were seen after these periods of treatment: 1) modifications of the structure, with thicker regions in the cup and a general decrease in the total volume according to the duration of exposure to the drug (about 4 times less than normal, 5,035 x 10(3) microns 3 vs 1,334 x 10(3) microns 3 after 8 h of treatment); 2) enlargement of the ventricular cavity and its closure, due to failure of approximation of retinal and pigmentary layers; 3) failure of lens development, with delay and impairment of pit formation and deformation of all structures; lens volume was less than normal (about 4 times less, 2,148 x 10(3) microns 3 vs 658 x 10(3) microns 3 after 8 h of treatment); 4) a general segregation of the cells making up the structure, principally in the more active proliferating zones. The local alterations found are described. PMID- 8490258 TI - Lectin histochemistry of salivary glands in the giant ant-eater (Myrmecophaga tridactyla). AB - The submandibular and buccal glands of the Giant Ant-eater (Myrmecophaga tridactyla) have been studied by means of a series of carbohydrate histochemical methods, including a broad spectrum of PO-lectin procedures. The seromucous cells (Gl. submandibularis) and mucous cells (Gl. buccalis) of the glandular acini, as well as the secretion in the excretory duct system exhibited very strong to strong reactions for neutral and acidic glycoconjugates. The serous cells of the buccal glands and the excretory duct cells reacted rather weakly. The different controls applied particularly emphasized that sialoglycoconjugates are the predominant ingredients of the saliva secreted. Lectin histochemical differentiation demonstrated a varying pattern of saccharide residues in these substances. In the submandibular glands the glycoconjugates (mostly proteoglycans) of the seromucous cells and the luminal secretion normally contained terminal beta-galactose and minor contents of terminal alpha-N acetylglucosamine. After sialidase digestion this cell type exhibited distinct amounts of sialic acid-beta-galactose and sialic acid-alpha-N acetylgalactosamine. Sialic acid was also clearly present in the tough interlobular connective tissue. The buccal glands showed a similar distribution of saccharide residues in the mucous cells. In the serous cells, however, acidic glycoproteins with sialyl residues were observed, also containing terminal alpha D-mannosyl, alpha-N-acetylgalactosaminyl, and beta-D-galactosyl residues. The cells of the excretory duct system of both gland types reacted weakly to moderately for terminal sugar residues (N-acetyl-D-glucosamine, N-acetyl-D galactosamine, beta-D-galactose). The results obtained are discussed in view of the specific feeding mode of the Giant Ant-eater, whereby high contents of sialoglycoconjugates (proteoglycans, glycoproteins) produced by the salivary glands warrant for the main function of the non-sticky saliva; i.e., to act as an effective lubricant during tongue movement. PMID- 8490259 TI - Cellular proliferation and/or differentiation can condition modifications in the expression of AgNORs in rat anterior pituitary cells during growth. AB - The expression of argyrophilic nucleolar organizer regions (AgNORs) was studied in the anterior lobe of the hypophysis of 1-, 7-, 14-, 28- and 80-day-old rats. Mean area and numbers of AgNORs per nucleus decreased during this period with a simultaneous increase of both nuclear area and mean AgNOR-particle area. Comparison of our data on AgNOR expression with previously reported data on the proliferative activity and cell maturation and differentiation of anterior pituitary cells during a similar period led us to conclude that, at least in our experimental model, variations in the expression of AgNORs are more related to phenomena of cellular maturation than to proliferative activity. PMID- 8490260 TI - Selective immunolabeling of early gestational cytotrophoblast and its neoplastic counterpart by the monoclonal antibody Ber-EP4. AB - This report presents preliminary observations on the distribution of an epithelial surface antigen in human trophoblastic cells studied with the monoclonal antibody Ber-EP4 by means of an immunoperoxidase technique. Three cases of gestational choriocarcinoma and 20 cases of both villous and extravillous trophoblast, including one complete hydatidiform mole and one exaggerated placental site, were examined with a panel of monoclonal antibodies against epithelial antigen (Ber-EP4), cytokeratin (AE1 and AE3), vimentin (VIM), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA), as well as with polyclonal antibodies against the beta subunit of human chorionic gonadotropin (hCG), human placental lactogen (hPL) and placental alkaline phosphatase (P1AP). While, as anticipated, all currently defined trophoblastic cell lines expressed low molecular weight cytokeratin only first trimester cytotrophoblastic cells and their neoplastic counterpart were found to possess the epithelial antigen detected by Ber-EP4. This distinctive property of the cytotrophoblast declined rapidly after eight weeks of gestational age but persisted in second trimester molar tissue and was prominently displayed in choriocarcinoma. By identifying the presence of cytotrophoblastic cell lines in malignancy more reliably than can be achieved with conventional panels of hCG, hPL and P1AP, Ber-EP4 has potential diagnostic utility in gestational trophoblastic disease. Our findings also suggest that the monoclonal anti-CEA antibody may be helpful in distinguishing between syncytiotrophoblastic cells and non-reactive multinucleate cells of the intermediate trophoblast. PMID- 8490261 TI - Morphological properties of human thyroid tumor cells in collagen gel culture and metastatic or invasive ability. AB - Using normal human thyroid cells and tumor cells, the reconstruction of various diseased cells in collagen gel as well as the relationship between the morphology of colonies in collagen-embedded culture and the biological behavior (benignity, malignancy, metastasis, and invasion) of the original tumors were studied. In collagen gel culture, normal thyroid cells reorganized follicle-like constructions, and follicular adenoma cells showed in vivo-like constructions. However, two different types of colonies were observed in cultures of cells from papillary carcinomas. One was the branching type with many outgrowths projecting to three dimensions and the other was the spherical type without any outgrowths. These spherical colonies were observed in all cases of papillary carcinoma, but varied from one case to another. Metastasis and invasion were detected during pathological examination in cases with a high ratio of spherical colonies. Our results indicate that cells from highly metastatic and invasive thyroid cancer form spherical colonies in the collagen gel culture, and that this collagen culture is a useful method for studying the heterogeneity of tumor cells as well as the metastasis and invasive ability of tumor cells in vitro. PMID- 8490262 TI - Tumor-infiltrating lymphocytes expressing IOT-10 marker. An immunohistochemical study of a series of 185 brain tumors. AB - The presence of IOT-10-positive lymphocytes among the tumor-infiltrating lymphocyte (TIL) population was studied in a series of 185 brain tumors. In most of the tumors, IOT-10-positive lymphocytes were identified, but generally they were scarce and masked among the tumor cells, suggesting that NK-cells exercise a poor participation in the tissular response against brain tumors. Isolated tumor cells showing IOT-10-positivity were found in low-grade astrocytomas, neurinomas and medulloblastomas. IOT-10-positivity on both tumor neuropil and tumor cells was considered a characteristic finding in oligodendrogliomas. The number of IOT 10-positive NK-cells in brain metastases and in cerebellar hemangioblastomas was comparatively greater than in other types of brain tumor. Since in brain metastases, the presence of IOT-10-positive NK-cells can be related to the tissular response to an extracerebral malignancy, their considerable presence in cerebellar hemangioblastomas is an enigmatic finding that deserves further attention. PMID- 8490263 TI - Characterization of the glycoconjugate sugar residues in developing chick esophageal epithelium. AB - The development of the esophagus in the chick embryo is characterized by remarkable morphological changes especially at the level of the epithelium. Using horseradish peroxidase-conjugated lectins (DBA, PNA, SBA, WGA, ConA, LTA, UEAI) we have studied, at the level of the esophagus of chick embryos from the 8th to the 21st day of incubation and of 1- and 2-day-old chicken, the evolution of the saccharidic moieties of glycoconjugates, which precedes and/or is concomitant with the epithelial morphological transformations. We have found differences in content and cellular distribution of oligosaccharides during the histogenetic processes which characterize the lining and glandular epithelium. Before the appearance of cilia and mucus secretion at the bathyprismatic epithelial cells, the sugar residues D-galactose-(beta 1-->3)-N-acetyl-D-galactosamine, beta-N acetyl-D-galactosamine and alpha-L-fucose were detected only at the luminal cell surface. These oligosaccharides were probably involved in giving rise to the polarization of the esophageal epithelial cells. The esophageal gland mucus was first characterized by the presence of alpha-L-fucose and afterwards also by the presence of D-galactose-(beta 1-->3)-N-acetyl-D-galactosamine, D-glucosamine and sialic acid. PMID- 8490264 TI - Effects of bombesin and neuromedin-B on the proliferative activity of the rat adrenal cortex. AB - Bombesin (BM) and neuromedin-B (NMB) exert similar biological effects, acting via two functionally distinct BM-receptor subtypes. The present study aimed to investigate whether BM and NMB stimulate the proliferation of rat adrenocortical cells and to compare their mode of action. Adult female rats were treated with a single subcutaneous dose of 3 micrograms BM or NMB. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique. BM administration resulted in a marked increase in the number of metaphases in zona glomerulosa (ZG) and zona fasciculata (ZF), and in the entire cortex. This increase appeared 24 h after injection in the ZG, and after 48 h in the ZF. NMB administration, on the other hand, caused a prompt increase in the number of metaphases in the ZG and entire cortex at 12 h, followed by a subsequent drop below the control level at 24 and 48 h of experiment. These findings indicate that BM and NMB enhance the proliferative activity of rat adrenocortical cells acting via different receptors or different mediators. PMID- 8490265 TI - In vitro antigen trapping by gill cells of the rainbow trout: an immunohistochemical study. AB - An in vitro assay was used to study the involvement of gill cells in the trapping and processing of particulate antigens. Gills were routinely processed for light microscopy after being placed in medium containing either Yersinia ruckeri O antigen-labelled fluorescent beads, unlabelled fluorescent beads, Y, ruckeri O antigen or formalin-killed Y. ruckeri, for 0, 30 s, 1, 5 and 30 min. Y. ruckeri formalin-killed cells, Y. ruckeri O-antigen and fluorescent beads labelled with Y. ruckeri O-antigen were taken in by gill epithelial cells as soon as 30 s after administration. In contrast, unlabelled fluorescent beads adhered to the epithelial cell membranes, but did not occur inside the gill cells. These results are discussed principally in relationship with the specificity of antigen trapping. PMID- 8490266 TI - Reverse lectin histochemistry: design and application of glycoligands for detection of cell and tissue lectins. AB - Plant and invertebrate lectins are valuable cyto- and histological tools for the localization of defined carbohydrate determinants. The well-documented ubiquitous occurrence of sugar receptors encourages functional considerations. Undoubtedly, analysis of the presence of vertebrate lectins in tissues and cells is required to answer the pertinent and tempting question on the physiological relevance of protein (lectin)-carbohydrate recognition in situ. Carrier-immobilized glycoligands, derived from custom-made chemical synthesis, enable the visualization of respective binding sites. Histochemically inert proteins or synthetic polymers with appropriate functional groups are suitable carrier molecules for essential incorporation of ligand and label. The resulting neoglycoconjugates can track down tissue receptors that are neither impaired by fixation procedures nor blocked by endogenous high-affinity ligands. Lectins, especially the receptors of the tissue under investigation (endogenous lectins), and appropriately tailored immobilized glycoligands or lectin-specific antibodies (when available) are complementary tools to test the attractive hypothesis that diverse, functionally relevant glycobiological processes within or between cells are operative. Concomitant evaluation of both sides of lectin histochemistry, namely lectins as tools and lectins as functionally important molecules in situ, will indubitably render desired progress amenable in our often still fragmentary understanding of the importance of tissue lectin and glycoconjugate expression and its regulation. PMID- 8490267 TI - Epithelial stem cells and their possible role in the development of the normal and diseased human breast. AB - The developing breasts of peripubescent girls consist of ducts and budded structures, which can subdivide to alveolar buds/lobules with advancing maturity and finally to secretory alveoli during pregnancy and lactation. Immunochemical reagents have been used to visualize the three major cell types in histological sections of mature/pregnant breasts, the epithelial cells which line ducts/ductules, the smooth muscle-like myoepithelial cells and the casein secretory alveolar cells. Ductal budded structures contain basal cells intermediate in immunocytochemical staining characteristics between epithelial and myoepithelial cells. Immortalization of primary epithelial cultures of normal breasts by simian virus 40 yields epithelial cell lines that can differentiate to myoepithelial-like and to secretory alveolar-like cells; similar cell types are identifiable in primary cultures. Immunocytochemical staining shows that both hyperplastic and neoplastic benign lesions contain myoepithelial-like cells, and, under suitable hormonal conditions, alveolar-like cells, but invasive carcinomas contain neither differentiated cell type. Primary cell cultures of benign hyperplastic and neoplastic lesions contain epithelial, myoepithelial-like and presumptive alveolar-like cells whilst malignant cell fractions of invasive carcinomas contain only epithelial cells. Spontaneously-immortalized epithelial cell lines from hyperplastic benign breast disease can generate myoepithelial like and alveolar-like cells, whilst standard epithelial cell lines from pleural effusions and novel epithelial cell lines from primaries of invasive carcinomas fail to differentiate to either cell type. It is suggested that epithelial/intermediate stem cells exist in a basal position predominantly in terminal structures of growing breasts, and that they are the major cell type involved in benign hyperplastic, benign neoplastic and malignant breast diseases. The acquisition of the malignant phenotype is associated with the carcinoma cells having a greatly impaired ability to differentiate to myoepithelial and to alveolar cells. PMID- 8490268 TI - Effects of chromium, copper, nickel, and zinc on longevity and reproduction of the cladoceran Moina macrocopa. PMID- 8490269 TI - Toxicity testing with coastal species of southeastern Brazil. Echinoderm sperm and embryos. PMID- 8490270 TI - Uptake of pentachlorophenol in fish of acidified and nonacidified lakes. PMID- 8490271 TI - Recovery of Nostoc muscorum previously exposed to some triazine and phenylurea herbicides. PMID- 8490272 TI - Preliminary laboratory investigation of the bioconcentration of zinc and iron in selected tissues of the banded tilapia, Tilapia sparrmanii (Cichlidae). PMID- 8490273 TI - Electron microscopic study of the liver of Tilapia nilotica exposed to neopybuthrin. PMID- 8490274 TI - Accumulation and transfer of copper by Oocystis pusilla. PMID- 8490275 TI - Heavy metals in oysters from a subtropical coastal lagoon associated with an agricultural drainage basin. PMID- 8490276 TI - Rapid respirometric toxicity test: sensitivity to metals. PMID- 8490277 TI - Cadmium uptake and distribution in three cultivars of Lactuca sp. PMID- 8490278 TI - Actin filaments disassembly: a novel step in the genesis of paraquat toxicity? PMID- 8490279 TI - Carious teeth as indicators to lead exposure. PMID- 8490280 TI - Validity of hair cadmium in detecting chronic cadmium exposure in general populations. PMID- 8490281 TI - Effects of sublethal concentrations of aflatoxins on the reproductive performance of mink. PMID- 8490282 TI - Assessment of indoor exposure to polycyclic aromatic hydrocarbons for urban poor using various types of cooking fuels. PMID- 8490283 TI - Membrane disordering effect of thiram as assessed by brain synaptosomal and erythrocyte membrane constituents. PMID- 8490284 TI - Trihalomethane induced alterations in the content of metallothionein and in the activities of heme metabolizing enzymes in rats. PMID- 8490285 TI - AIDS: impact on the health care system. PMID- 8490286 TI - The high cost of hospital trauma care: an analysis of hospital length of stay, injury severity score, case mix index, and reimbursement-to-cost ratio. AB - We conducted a study to evaluate reimbursement characteristics for an urban hospital providing a high volume of trauma care. Complete clinical and financial data for 209 trauma patients admitted to the Bronx Municipal Hospital Center during September 1990 were entered into a trauma registry. Patients were categorized into three groups. Group 1 fulfilled criteria for reimbursement using the New York State Major Diagnostic Category 25 (NYSMDC 25) for trauma. Group 2 patients fulfilled New York City Emergency Medical Service 911 criteria for transport to a level 1 trauma center. Group 3 patients did not fit either category. Analysis included age, race, sex, length of stay, injury severity score, case mix index, payer source, and reimbursement-to-cost ratio. Of the patients studied, 77.5% were men. Hispanic, African-American, and white patients constituted 40.2%, 26.3%, and 17.2%, respectively, of the study population. The payer mix was 36.6% Medicaid; 20.8% self-pay; 19.1% no fault; 9.6% Blue Cross; 5.5% Medicare; 5% commercial; and 3.3% other. The study demonstrated that criteria for group 1 and group 2 define patients who constitute a distinct clinical group by injury severity score. As expected, the length of stay and case mix index were significantly higher for group 1, but they did not differ between group 2 and group 3. Group 1 was a small proportion (7.7%) of trauma patients admitted to the Bronx Municipal Hospital Center level 1 trauma center. Trauma admissions were treated at a net loss, with a projected high annual deficit of $5.3 million.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490287 TI - Effect of cholecystokinin on food intake at different stages of the estrous cycle in female rats. AB - Effects of cholecystokinin octapeptide (CCK-8) on feeding behavior were examined in male and female rats. After an 18-hour fast, ad lib food intake for 30 minutes was measured for each rat. In male rats, food intake measured for 30 minutes was significantly decreased by intraperitoneal injection of 0.25 to 1 microgram/kg of CCK-8 in a dose-dependent manner. The satiety effect of CCK-8 was blocked by L 364,718 (20 nmol/kg), a specific cholecystokinin receptor antagonist. In female rats, food intake at proestrus and estrus was significantly less than that at diestrus. Food intake of female rats at diestrus and metestrus was significantly decreased by an intraperitoneal injection of CCK-8 prior to feeding, but it was not affected at proestrus and estrus. The effect of CCK-8 on food intake at diestrus and metestrus was dose dependent and was nearly abolished when 20 nmol/kg of L-364,718 was administered simultaneously. The results of this study suggest that stages of the estrous cycle affect feeding behavior of rats. Further, cholecystokinin's regulatory action on feeding behavior appears to be effective at diestrus and metestrus, but not at proestrus and estrus. PMID- 8490288 TI - Spirochetal antibodies in tropical spastic paraparesis: their significance. AB - The prevalence of antibodies to Treponema pallidum and Borrelia burgdorferi was investigated in Jamaicans with tropical spastic paraparesis (TSP). A significantly higher prevalence of reactive serologic tests for syphilis (STS) was found in TSP patients (35.0%) when compared with controls (14.5%; P < .001). Venereal Disease Research Laboratory (VDRL) test titers less than 1:8 were obtained in 88.4% of reactive sera from patients and in all reactive sera of controls. The biologic false-positive rate was also significantly higher in TSP patients (P < .05). A higher frequency of a reactive STS was observed in TSP patients (P < .01) and controls (P < .001) more than 40 years of age. The prevalence of reactive serologic tests for syphilis in TSP patients younger than 40 years was also higher than in controls in this age group (P < .1). The prevalence of positive immunofluorescent antibody tests and enzyme immunoassay for antibodies to B burgdorferi was similar in sera of TSP patients (12.5%) and healthy controls (10%). However, none of the sera was positive by Western immunoblot. Leptospiral antibodies were not present in any serum tested. This study's data do not support an etiologic role for treponemal disease in tropical spastic paraparesis, but rather suggest that the high prevalence of reactive STS in Jamaicans is multifactorial. PMID- 8490289 TI - Effect of cold stress on coronary sinus blood flow in patients with scleroderma. AB - The mechanism of cardiac involvement in scleroderma is not known. Histologic studies of the myocardium in patients who died of scleroderma revealed that half had myocardial damage. Characteristic involvement ranges from focal contraction band necrosis to diffuse fibrosis despite the absence of obstructive coronary artery disease of the major epicardial vessels. These findings suggest that scleroderma heart disease might result from episodic reduction of coronary blood flow due to abnormalities of coronary vasomotor tone. Studies using cold pressor thallium 201 myocardial perfusion scans support this hypothesis. Our study measured coronary blood flow during hand immersion in ice water at cardiac catheterization to determine whether patients with scleroderma had an abnormal coronary blood flow response. Coronary sinus blood flow was measured using a thermodilution method. Five patients with scleroderma were compared with 5 control subjects. All patients and controls had normal coronary angiograms. The coronary blood flow at baseline in the scleroderma and the control group (130 +/- 33 mL/min and 86 +/- 27 mL/min, respectively) was not significantly different. During the cold pressor test, both groups had a small, insignificant increase in coronary blood flow from baseline to 60 seconds (130 to 144 mL/min, scleroderma patients; 86 to 89 mL/min, control subjects). Our findings suggest that the cold pressor test does not cause an abnormal increase in coronary vasomotor tone or an absolute reduction in coronary blood flow in patients with scleroderma, as previously suggested by thallium 201 cold pressor studies. PMID- 8490290 TI - [Differential diagnostic strategies in uncertain vision disorders]. AB - The differential diagnosis of visual disturbances of unclear origin can cause major problems in ophthalmology, especially if there are no functional defects or if functional defects cannot be explained by morphological findings after an extensive regular ophthalmological investigation. The aim of this paper is to present strategies that allow subtle visual disturbances to be related to certain groups of functional defects. Especially simple investigations are emphasized that lead quickly to a well-founded possible diagnosis that helps both the ophthalmologist and patient save time and cost-consuming deviations. The key investigations are: (1) a symptom-oriented case history; (2) exclusion of refractive problems by pin-hole test, retinoscopy and ophthalmometry; (3) the swinging flashlight test; (4) ophthalmoscopy of the macula and optic disc; (5) visual field. A flow chart is presented that explains the strategy of additional special investigations based on the results of the key findings in order to approach quickly the cause of a visual disturbance. Some of the more common causes of visual disturbances of unclear origin are discussed, including some major therapeutic principles. PMID- 8490291 TI - [New diagnostic aids in automatic perimetry]. AB - The Conformity Analysis is a new procedure for objective recognition of specific defect patterns in automated perimetry. The "Conformity Index," the measure of conformity between the distribution of defect values and several standard defect patterns, is calculated from the ratio of global variance and mean variance in particular regions. Using 68 visual fields from 68 normal persons, we determined normal values and limits of the Conformity Index for seven standard defect patterns: hemifields right-left, hemifields upper-lower, quadrants, sectors, rings with 5 degrees and 10 degrees radius interval and the perimetric nerve fiber bundles of Weber and Ulrich. The evaluation of 148 visual fields (68 normal eyes, 80 eyes with chronic glaucoma and all stages of damage) by both the Conformity Index and two experienced clinicians revealed an identical result in 89%. Using the Conformity Analysis in 37 cases of pituitary adenoma, we could objectively identify quadrants, sectors and hemifields right-left to be the most common defect patterns in this disease. In glaucoma fields with marked damage (n = 46), the most frequent pathological Conformity Index was the index for perimetric nerve fiber bundles. PMID- 8490292 TI - [In incipient glaucoma the pattern electroretinogram displays diffuse, retinal damage]. AB - The pattern electroretinogram (PERG), a noninvasive tool to measure the activity of retinal ganglion cells, shows changes in early glaucoma. We wanted to investigate whether or not the PERG is preferentially affected when the Bjerrum area is stimulated. We recorded the PERG from 17 eyes in 17 patients with initial stages of visual field defects due to open-angle glaucoma and from 10 eyes in 10 normal subjects. Counter-phasing checkerboard patterns were used as visual stimuli with a check size of 0.8 degrees at 16 reversals/s and 98% contrast. Three visual field extents were stimulated: (1) full screen (31 degrees x 27 degrees), (2) central stimulation with a diameter of 14 degrees, (3) peripheral stimulation = full screen with central mask of 14 degrees in diameter. The latter stimulus covers the regions where traditionally glaucomatous defects are expected early. In glaucoma patients, there was a significant decrease in the PERG amplitude compared to normals. This reduction was very similar for all three stimuli (42%, 52% and 47%, respectively). Thus, the PERG amplitude is reduced to a similar degree both in regions of the visual field where early damage is found (Bjerrum area) and in the central area. This result suggests that in early glaucoma there is focal as well as diffuse retinal damage. PMID- 8490293 TI - [The Freiburg Vision Test. A computer-assisted procedure with sequential strategy]. AB - Single Landolt Cs were presented in one of four positions on a monitor. Subjects responded by pressing one of four buttons (forced choice). A computer selected the size of the Landolt Cs on a logarithmic scale using the "Best PEST" algorithm (Best Parameter Estimation by Sequential Testing), a modern procedure to measure psychophysical thresholds. For comparison, conventional measurements according to DIN 58220 (Deutsche Industrie Norm) were performed with Landolt Cs projected in eight positions, using three out of five correct responses as the threshold criterion. Examination of 23 patients (most of them with senile cataract) did not show any significant difference between the two tests in either visual acuity or reproducibility on two consecutive days. The coefficients of variation between sessions were 22% for the Freiburg test and 26% for the DIN test and 18% between the two tests, pooled over two sessions. The Freiburg acuity test thus appears to be numerically equivalent to the DIN 58220 procedure. In addition, it has a number of advantages: (1) examiner-dependent variability is reduced; therefore, the test can be used by inexperienced examiners; (2) the forced choice technique is used rigorously; (3) mistakes in confounding oblique directions are largely avoided; (4) the procedure is about twice as fast. PMID- 8490294 TI - [The effect of triamterene on the ERG of Long-Evans rats]. AB - Dopamine is an important mediator of the neuronal adaptation mechanism of the retina. Tetrahydrobiopterin (BH4) is cofactor of the rate-limiting enzymatic tyrosine-hydroxylase step in the biosynthetic pathway of dopamine. This enzymatic step causes an oxidation of BH4 to dihydrobiopterin (BH2), which is reduced again to BH4 by action of dihydropterin-reductase (DHPR) and dihydrofolate-reductase (DHFR). Triamterene, a pterin derivate, is known to induce DHFR after initial inhibition. Concomitant elevation of retinal BH4 will result in a higher dopamine concentration. ERG changes of Long-Evans rats mediated by this triamterene effect on dopamine concentration were examined after the rats received triamterene with tap water in two experimental series for 5 and 11 days. After 5 days of triamterene administration a significant decrease of scotopic a- and b-wave ERG amplitudes were registered. After 11 days of triamterene application the decrease could be shown to be even more substantial. This effect was completely reversible: 10 weeks after cessation of triamterene supply ERG amplitudes increased to previous levels. The observed transient ERG changes support the concept of biopterin as an mediator of neuronal adaptation mechanisms of the retina. PMID- 8490295 TI - [Right shift in the EOG]. AB - The evaluation of 1000 consecutively recorded EOGs showed in 10% of all cases a phenomenon which we called right shifting of the EOG: Dark trough and/or light peak were delayed. In cases of macular disease, atypical pigment degeneration and in control records during Chloroquine therapy we found right shifting more frequent. PMID- 8490296 TI - [Blue-sensitive mechanisms in pattern ERG and VEP]. AB - Pattern onset-offset ERGs and VEPs in response to square-wave stripe patterns of different wavelengths and spatial frequencies under chromatic yellow adaptation (two-channel Maxwellian view) were studied in three subjects. One channel provided a steady homogeneous adapting field of 570 nm, while the other channel, containing the patterns, was superimposed on the adapting field (33 degrees). The spectral sensitivity curve of the ERG had a prominent peak in the blue (460 nm) and a shoulder in the red and green (above 500 nm). For wavelengths below 500 nm the shape of the psychophysically determined sensitivity curve to the onset and offset of the pattern was in close agreement with the electroretinal sensitivity curves determined for a low-amplitude criterion. With almost all wavelengths there were two components in the same VEP response at the same time: a slow negative wave with maximum sensitivity at 460 nm and an earlier fast positive component with maximum sensitivity in the red-green region. When the spatial frequency of a 460 nm test pattern was varied under yellow adaptation the onset response in the ERG showed only very slight spatial tuning. In the onset response of the VEP, however, the slow component showed prominent spatial tuning (around 2 c/deg) under the same conditions. PMID- 8490297 TI - [Pattern-induced flicker colors. An ophthalmologic examination method]. AB - The pattern-induced flicker colours (PIFC), which belong to the subjective colours, are presented here as a method of investigating diseases of the eye and the visual track. Starting with Benham's top, new methods are elaborated for producing PIFC by means of rotating black and white discs and a computer controlled black and white monitor. The investigations were performed in 40 normal and 111 pathological cases. A differentiation is made concerning the neuronal X-Y system. Different deficiencies result from different diseases. The PIFC are particularly suitable for the differential diagnosis of the neuritis nervi optici. PMID- 8490298 TI - [Reference to the Abney effect within the scope of linear opponent-color theory]. AB - The Abney effect states that desaturation of spectral colours does not only change their chromatic saturation but also their hue. By means of Hering's perceptual criteria "neither blue nor yellow" and "neither green nor red" and heterochromatic brightness matching, chromaticity loci were measured in a visual tri-stimulus colorimeter; the loci served for construction of an opponent-colour triangle and the associated opponent-colour space. The chromaticity line resulting from the perceptual criterion "neither green nor red" deviated markedly -as an expression of the Abney effect--from a straight line. This phenomenon was captured by piecewise linearizing. The transformation of the (known) fundamental colour space, which may be interpreted as a cone excitation space, onto the opponent colour space thus gained yielded an explicit opponent-colour theory that reproduces some aspects of the Abney effect. PMID- 8490299 TI - [Surgical correction of high degree corneal astigmatism]. AB - Many patients with high-grade corneal astigmatism cannot tolerate correction with spectacles or contact lenses. In contrast to myopic patients, in these cases visual rehabilitation can only be achieved surgically. In 1990 we started to perform modified corneal T-incisions in cases with high-grade astigmatism and intolerance to glasses or contact lenses. According to the eligibility criteria for selection of patients only 12 eyes were operated on in 1990: 9 eyes were affected by congenital high-grade astigmatism (mean 5.25 D); 1 had 8.5 D astigmatism after perforating injury, keratoplasty and cataract operation; 1 had 2.5 D astigmatism after perforating injury; and 1 eye showed 5.0 D astigmatism following cataract surgery. Without exception, the astigmatism was significantly reduced, from a preoperative mean of 5.25 D to a mean of 2.0 D postoperatively. The most impressive change was the improvement of uncorrected visual acuity. No complications were observed and none of the patients complained of postoperative glare. These results have encouraged us to continue with surgical correction of high-grade corneal astigmatism. PMID- 8490300 TI - [Endothelial cell transplantation in a model]. AB - Human donor corneas that were unsuitable for transplantation were denuded of their endothelium and then used as substrates for seeding in vitro cultured human or porcine corneal endothelial cells. Only cells that expressed an endothelial like morphology in vitro formed a monolayer on the denuded matrix whereas fibroblast-like cells showed no redifferentiation. The maximal achieved cell density was 3,500 cells/mm2 if porcine cells were used and 1,800 cells/mm2 for human cells. Adhesion of the cells was best if the subendothelial matrix was carefully prepared mechanically. Moreover, cell seeding was improved by slight centrifugation. Fibroblast growth factor (FGF), which enhanced endothelial cell proliferation in vitro, did not influence proliferation after cell transplantation, but seemed to allow better regeneration of the newly formed monolayer on the corneas. PMID- 8490301 TI - [Duration of fluorescein diacetate in corneal endothelium]. AB - Fluorescein diacetate (FDA) is a suitable substance for vital staining of corneal endothelium. Uptake and metabolism is an active process. This means that a fluorescing cell must be functionally intact. The duration of endothelial fluorescence is limited and should be tested in an experimental study. Cultured endothelial cells (calf aorta endothelial cells) were stained by FDA and the loss of fluorescence time registered. We tested corneal buttons in the same way. The cultured endothelial cells showed no fluorescence after 2 h and the corneal buttons after 40-50 min. The fluorescence of FDA-stained endothelial cells decreases both in cultured cells and in whole corneal buttons, but this is not a sign of loss of endothelial viability. This fact must be taken into consideration when interpreting the results of FDA staining. PMID- 8490302 TI - [HLA typing in high risk keratoplasty]. AB - Improved microsurgical techniques and better immunosuppressive treatment have led to an increase in the number of corneal transplantations. However, graft rejection due to a disparity between donor and recipient major histocompatibility antigens remains the major complication. The risk of graft rejection is further increased in patients with vascularized graft beds and in presensitized persons. Well-designed experimental studies and clinical experience have clearly shown the importance of class-I-antigens. However, class-II antigens have not yet been studied to the same extent. METHODS: Multiorgan donors and corneal graft recipients were HLA typed using the lymphocytotoxicity test previously described by Terasaki. The recipients were typed retrospectively. Cadaver corneal graft donors were typed using a novel HLA typing technique on retinal pigment epithelial cells, as previously described by us. Postoperatively, all recipients were routinely examined for rejection over a period of 2 years. RESULTS: Graft rejection was observed in 25% of the 133 high-risk patients. Of the 13 class-I typed patients who showed a rejection 9 persons had two or more major histocompatibility mismatches. Of the 12 patients without rejection problems only 5 had two or more HLA class-I-mismatches. Of the patients with one or two matches at the HLA-DR locus there were only 4 out of 9 patients with at least one graft rejection; 5 out of 6 patients showed no signs of rejection. CONCLUSIONS: Mismatches at either class-I- or class-II- gene loci lead to a higher frequency in corneal graft rejection. Apart from the major histocompatibility mismatches, other factors also influence graft rejection, such as the distance between the corneal transplant and corneal vessels, presensitization, and the indication for corneal grafting. If we are to define the factors influencing graft rejection better and further increase our knowledge on the role the major histocompatibility antigens play in corneal graft rejection in a larger patient group, then cooperation with other transplantation centers will be required. PMID- 8490303 TI - [Silicone impression procedure. Principles for determining ablation and healing parameters in vitro and in vivo]. AB - Topometry and measurement of photoablation patterns are key questions for keratorefractive photoablation. So far, ablation rates have been determined either by tissue perforation or histological micrometry. A cast of irradiated cornea was made by using a 2-component silicon that polymerizes within minutes, thus preserving the corneal topography immediately after photoablation. The silicon surface is extremely smooth and the accuracy of the cast better than 1 micron. Reproducibility and long-term stability were proven for casts of photoablated PMMA. Thus ablation rates and profile, volumetry and topometry can be determined at any time. The method was applied for 193 nm excimer and 2.94 microns Er:YAG laser in vitro irradiation of the human cornea. Ablation rates in Bowman's layer and stroma were observed for various radiant energies and distinct pulse numbers. The average ablation rates are in agreement with published data. It could be demonstrated that there was an incubation effect for the first pulses. The method feasibility for in vivo measurement was also proven in an animal model. After excimer photoablation in rabbit eyes (beam diameter 3.5 mm, radiant energy 185 mJ/cm3, ablation rate 0.3 micron/pulse), wound healing was recorded: for the right eye silicon casts were molded at three different moments. For the left eye only photographs were taken. There was no difference in the time course of wound healing, so the silicon does not seem to interfere with repair mechanisms of the corneal epithelium. No side effects were observed. PMID- 8490304 TI - [Photoablation of the cornea with pulsed 2790 nm ErCr:YSGG laser irradiation. Basic studies]. AB - The potential of 3 microns solid-state lasers as an alternative to excimer lasers for photoablative corneal surgery was investigated. A Q-switched ErCr:YSGG laser (2790 nm, 200 ns) was used for irradiation of porcine corneas and agar-agar samples. Mechanical tissue effects (stroma, endothelium) were documented by micromorphology. Laser-induced shock-waves were analyzed by piezo-electric transducers. No sharp ablation threshold, as in excimer laser photoablation, could be determined. Energy fluences < 2 J/cm2 led to dehydration of the irradiated samples. Higher fluences are necessary for the evaporation of tissue water to be so vigorous that the tissue matrix is expelled along with the organic matrix. At high fluences, the ablation rate exceeds the absorption depth of the laser radiation (up to 25 microns/pulse). At fluences between 2.5 and 28 J/cm2 the thermal necrosis zone adjacent to the crater was 7 +/- 3 microns. The intensity of the laser-induced acoustic shock waves can peak to some hundred bar. Small gas bubbles up to 1 mm were found in the surrounding area of the ablation crater. Apparently, they were pressed between the collagen lamellas by the explosive force of the ablative process. In deep excisions (> 75%) endothelial defects underneath the beam axis could be documented. Large-area tissue ablation, with a resolution in the range of 1 micron, as necessary in myopia correction, will not be possible with the present generation of ErCr:YSGG lasers. Its high ablation rate makes this laser suitable as a cutting (astigmatism, keratoplasty, vitreous surgery) and drilling (glaucoma) device. PMID- 8490305 TI - ["To educate myself, quite as I am". On Education in Germany]. PMID- 8490306 TI - [Diabetic retinopathy. Epidemiology, risk factors and staging]. PMID- 8490307 TI - Effects of etomidate and hypothermia on cerebral metabolism and blood flow in a canine model of hypoperfusion. AB - Etomidate is a nonbarbiturate hypnotic agent which, like the barbiturates, decreases the cerebral metabolic rate of oxygen consumption (CMRO2) 35-50%. The present studies assessed whether etomidate decreased CMRO2 through temperature dependent mechanisms and whether the combination of etomidate and moderate hypothermia (28 degrees C) decreased CMRO2 more than hypothermia alone. Nineteen anesthetized dogs were treated with saline, etomidate (burst-suppressive doses), etomidate with hypothermia, or hypothermia alone. Etomidate did not affect (p > 0.05) the mean arterial pressure (MAP, mm Hg) but modestly lowered the heart rate [HR; 124 +/- 6 to 105 +/- 14, (mean +/- SEM); p < 0.05] whereas hypothermia (without or with etomidate) lowered (p < 0.05) both MAP (141 +/- 4 to 116 +/- 5 and 135 +/- 6 to 81 +/- 7) and HR (135 +/- 14 to 84 +/- 3 and 135 +/- 10 to 69 +/ 5, respectively). Etomidate administration did not result in a change (p > 0.05) in the esophageal, brain parenchymal, or subdural temperature. CMRO2 (ml/100 g/min) decreased (p < 0.05) during etomidate administration (3.2 +/- 0.4 to 1.7 +/- 0.2) and hypothermia (3.5 +/- 0.2 to 1.1 +/- 0.2), but the addition of etomidate to hypothermia did not further reduce CMRO2 in the animals (3.1 +/- 0.5 to 1.3 +/- 0.2) despite decreasing their brain hemispheric electrical activity from 9 +/- 1 Hz to a burst-suppressive state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490308 TI - Neuron-specific enolase as a marker of in vitro neuronal damage. Part I: Assessment of neuron-specific enolase as a quantitative and specific marker of neuronal damage. AB - Enolase in cerebrospinal fluid is a sensitive marker for many types of neurological injuries including head injury and ischemia. We assessed neuron specific enolase (NSE) as a quantitative and specific biochemical marker of neuronal damage in an experimental model of kainate neurotoxicity. Rat hippocampal cultures were treated with various concentrations of kainate. NSE release into the culture medium was compared with neuronal death estimated either by direct cell counting or by lactate dehydrogenase (LDH) release, largely used to quantify neuronal injury. A dose-response relationship was observed between kainate concentration and the amount of NSE released (r = -0.69; p < 0.05) as well as a significant correlation between NSE release and neuronal death (r = 0.64; p < 0.05). Likewise, a significant correlation was found between LDH and NSE release (r = 0.85; p < 0.05). The specificity of NSE as an indicator of neuronal death was demonstrated using immunocyto-chemistry labeling and measurement of NSE release by pure astrocyte cultures. We concluded that NSE is a reliable, quantitative, and specific marker of neuronal injury. PMID- 8490309 TI - Neuron-specific enolase as a marker of in vitro neuronal damage. Part II: Investigation of the astrocyte protective effect against kainate-induced neurotoxicity. AB - The protective effect of astrocytes on hippocampal neurons against kainate induced toxicity was investigated using neuron-specific enolase as an indicator of neuronal death. Astrocyte-rich and astrocyte-poor mixed rat hippocampal cultures were submitted to various concentrations of kainate. At each kainate concentration, the amount of NSE released by neurons was significantly greater in astrocyte-poor than in astrocyte-rich cultures (p < 0.05). This protective effect was not observed when neuronal survival was tested on astrocyte-poor cultures in astrocyte-conditioned culture medium with or without 10(-4) M kainate. In conclusion, astrocytes significantly attenuate kainate toxicity on hippocampal neurons, and this effect is not mediated by a diffusible factor. PMID- 8490310 TI - Effect of cerebral venous congestion on the pressure-volume index in the evaluation of intracranial pressure dynamics. AB - Translocation of cerebrospinal fluid (CSF) between the intracranial and spinal subarachnoid space was blocked by ligating the cervical spinal core in eight cats under pentobarbital and nitrous oxide anesthesia, and the effects of cerebral venous congestion on the pressure-volume index (PVI), a measure relating the change in intracranial volume, and the logarithm of intracranial pressure (ICP) were evaluated. The changes in the volume-pressure response (VPR), a measure of intracranial elastance, were calculated simultaneously. Cerebral venous congestion was induced by lowering the head relative to the level of the heart by tilting the trunk of the animals to 20 degrees below horizontal. The presence of venous congestion was confirmed by an increase in the sagittal sinus pressure (SSP). The body position was shifted from horizontal prone (H1 group) to head down tilt (D1 group) in four animals (group 1) and from head-down tilt (D2 group) to horizontal prone (H2 group) in the other four animals (group 2), and PVI and VPR were determined in each group. The changes in ICP and SSP with change of body position in group 1 were not significantly different from those in group 2, with both pressures changing by 7-8 mm Hg. PVI showed no significant differences between the H1 group and H2 group or between the D1 group and D2 group. The mean (+/- SEM) PVI for all measurements in the head-down tilt position (D1 and D2 groups) was significantly higher (0.50 +/- 0.02 ml; p < 0.01) than in the horizontal position (H1 and H2 groups; 0.35 +/- 0.02 ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490312 TI - Capnography in younger patients. PMID- 8490311 TI - An unexpected complication of encephalocele repair. PMID- 8490313 TI - On Rock & Roll and Index Medicus. PMID- 8490314 TI - Neurosurgical intensive care unit organization and function: an American experience. AB - This article describes the organization and function of a university-based neurosurgical intensive care unit. The unit's success has been based in part on its physical structure and in larger part on its organization. Patients are comanaged by a team of neurosurgeons and anesthesiologist intensive care specialists, who receive twice-weekly input from all other participating patient care specialists, including nurses, physical therapists, social workers, and others. This type of approach promotes teamwork and fosters mutual respect among the team. It also improves patient care and, frequently, outcome. PMID- 8490315 TI - Local versus general anesthesia for lumbar percutaneous discectomy. AB - Ninety-two adult patients scheduled for automated percutaneous discectomy (PERC) were assigned to receive either local anesthesia supplemented with monitored i.v. analgesia (MIVA) or general endotracheal anesthesia (GA-LITE). Patients were examined 1 week post-PERC for the presence of new paresthesias, and they completed a questionnaire 6-18 weeks after PERC about changes in their pain. Sixty-four percent of MIVA patients and 83% of GA-LITE patients had diminished pain following PERC. Results did not show any difference between the two groups for new paresthesias after PERC. There were no differences in postoperative pain medication requirements, but the GA-LITE group reported more postoperative nausea, vomiting, and sore throat. GA-LITE patients averaged 1.06 +/- 0.3 h in the recovery room compared with 0.70 +/- 0.3 h for MIVA patients. Although the use of general anesthesia for PERC has been contraindicated because of fear of damaging the nerve root in the sleeping patient, we conclude that general anesthesia does not increase nerve injuries attributable to instrumentation. However, general anesthesia did cause a higher incidence of minor complications such as nausea, vomiting, and sore throat in the immediate postoperative period than did MIVA. PMID- 8490316 TI - Transcranial Doppler monitoring during induction of anesthesia: effects of propofol, thiopental, and hyperventilation in patients with large malignant brain tumors. AB - Disturbed autoregulation and CO2 reactivity have been reported in patients with brain tumors. Therefore, we decided to monitor the cerebrovascular effects of anesthetic drugs and hyperventilation. Transcranial Doppler sonography (TCD) can measure noninvasively alterations of flow velocities (v) and cross-sectional vessel area (VA) in large brain arteries. Twenty-eight patients with large malignant brain tumors in the territory of the middle cerebral artery (MCA) randomly received propofol or thiopental for induction and maintenance of anesthesia. Mean arterial pressure (MAP), heart rate (HR), and TCD parameters (vMCA and VA of the tumor or nontumor side) were determined at six data points (DP). The first measurements (MAP, HR, and TCD of the nontumor side) were performed before (DP I) and 60 s after (DP II) induction of anesthesia with either 2 mg/kg propofol or 4 mg/kg thiopental. After intubation and normoventilation (50% O2 in air), 0.05-0.1 mg/kg midazolam and an alfentanil infusion (100 micrograms/kg x h) were initiated. Then MAP, HR, vMCA, and VA of the tumor side were analyzed before (DP III) and 60 s after (DP IV) either propofol (1 mg/kg) or thiopental (2 mg/kg) were given. Finally, the effects of hyperventilation on HR, MAP, vMCA, and VA (tumor side) were determined (DP V and VI). Mean +/- SD, thiopental or propofol reactivity (non-tumor and tumor side) and CO2 reactivity (tumor side) were calculated; statistical comparison between DP I and II, III and IV, and V and VI was performed by paired t tests (p < 0.05). Unpaired t tests were used to evaluate differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8490317 TI - Lactate and postischemic recovery of energy metabolism and electrical activity in the isolated perfused rat brain. AB - The aim of the present study was to evaluate whether lactate can maintain the energy metabolism and electrical activity of isolated perfused rat brain in the absence of glucose. To exhaust cerebral glucose stores and simultaneously raise endogenous lactate, complete ischemia was induced. After ischemia, when a glucose free perfusate was supplied, restoration of interstitial potassium (Ke+), cortical discontinuous current (DC) potential, electroencephalogram (EEG) activity, and ATP and phosphocreatine (PCr) was not significantly different from postischemic recovery findings when a glucose-containing perfusate was used. In the group receiving glucose-free perfusate, postischemic application of 1 mM iodoacetic acid did not inhibit the recovery of electrical activity, Ke+, or DC potential. After recovery of Ke+ in glucose-free reperfusion, a 20-30-Hz EEG pattern appeared and was maintained for about 20 min followed by disappearance of spontaneous electrical activity. An abrupt increase of Ke+, a steep negative DC shift, and a substantial decrease of ATP and PCr occurred after about 22 min of reperfusion. During the first 5 min of glucose-free reperfusion, consumption of lactate was significantly higher (0.89 mumol/g wet weight/min) than during reperfusion with medium containing glucose (0.41 mumol/g ww/min). Increasing amounts of tissue lactate prolonged maintenance of electrical function in glucose free reperfusion. This correlation could not be found for free fatty acids. In conclusion, after a few minutes of ischemia, the brain is able to recover cellular ion transport and electrical activity without a supply of glucose, preferentially by combustion of lactate accumulated in brain tissue. This mechanism is only useful during a limited time period until the lactate accumulated during ischemia is combusted. PMID- 8490318 TI - Spatial and temporal factors in the role of prefrontal and parietal cortex in visuomotor integration. AB - The effects of reversible lesion--by cooling--of dorsolateral prefrontal and posterior parietal cortex were studied in rhesus monkeys performing a cognitive visuomotor integration task. Correct performance required the use of a learned set of cue-response contingencies, some spatial and some nonspatial; in some cases, the task required the short-term retention, through a delay, of the color of the cue or its implicit response direction. Prefrontal cooling impaired performance of the task regardless of its spatial demands, an effect that increased with delay. Parietal cooling, on the other hand, only impaired performance if the task demanded the processing and retention of spatial information (i.e., if spatial active memory was required). Parietal effects were not related to delay. Both prefrontal and, even more, parietal cooling increased response time in all task contingencies. Thus, the results dissociate the respective contributions of the prefrontal and the posterior parietal cortex to the temporal and spatial aspects of information processing in visuomotor performance. They indicate that posterior parietal areas participate in spatial processing and in active memory of spatial information, whereas prefrontal areas subserve a broader role of visuomotor processing and cross-temporal integration of both spatial and nonspatial information. PMID- 8490319 TI - Low-affinity nerve growth factor receptor (p75NGFR)- and choline acetyltransferase (ChAT)-immunoreactive axons in the cerebral cortex and hippocampus of adult macaque monkeys and humans. AB - Low-affinity nerve growth factor receptor (p75NGFR) was analyzed in the adult monkey and human cerebral cortex and hippocampus by light and electron microscopic immunohistochemistry using a mouse monoclonal antibody raised against human p75NGFR. In the monkey only, the morphology and laminar and areal distribution of the p75NGFR-immunoreactive fibers were further compared with distribution of the ACh-synthesizing enzyme ChAT. We found that the p75NGFR fiber distribution is remarkably dense throughout the cerebral neocortex and highly similar in homologous cortical areas of monkey and human. In both species, p75NGFR-immunoreactive fibers are contracted in layers I, II, and the superficial portions of layer III in all frontal, parietal, temporal, and occipital areas examined. In the primary visual and somatosensory cortices, dense p75NGFR fiber plexuses are additionally found in layer IV. In the hippocampal formation, this fiber system is most dense in the CA2 and CA3 subfields as well as in the molecular and polymorphic layers of the dentate gyrus. The distribution and characteristics of the p75NGFR-positive fibers in the primates correspond almost exactly to those of the cholinergic fiber system as revealed by ChAT immunohistochemistry in the present study as well as in the literature (Lewis, 1991; Mesulam et al., 1992; Voytko et al., 1992). Electron microscopy revealed that p75NGFR is associated mainly with axonal membranes and portions of the axoplasm in labeled fibers. Although the function of p75NGFR is still a matter of debate, its widespread distribution opens up new questions regarding its physiological role in the large and functionally differentiated cerebral cortex and hippocampus of monkey and human. PMID- 8490320 TI - Comparison of intrinsic connectivity in different areas of macaque monkey cerebral cortex. AB - We have used small injections of biocytin to label and compare patterns of intraareal, laterally spreading projections of pyramidal neurons in a number of areas of macaque monkey cerebral cortex. In visual areas (V1, V2, and V4), somatosensory areas (3b, 1, and 2), and motor area 4, a punctate discontinuous pattern of connections is made from 200-microns-diameter biocytin injections in the superficial layers. In prefrontal cortex (areas 9 and 46), stripe-like connectivity patterns are observed. In all areas of cortex examined, the width of the terminal-free gaps is closely scaled to the average diameter of terminal patches, or width of terminal stripes. In addition, both patch and gap dimensions match the average lateral spread of the dendritic field of single pyramidal neurons in the superficial layers of the same cortical region. These architectural features of the connectional mosaics are constant despite a twofold difference in scale across cortical areas and different species. They therefore appear to be fundamental features of cortical organization. A model is offered in which local circuit inhibitory "basket" interneurons, activated at the same time as excitatory pyramidal neurons, could veto pyramidal neuron connections within either circular or stripe-like domains; this could lead to the formation of the pattern of lateral connections observed in this study, and provides a framework for further theoretical studies of cerebral cortex function. PMID- 8490321 TI - Magnetoencephalography reveals two distinct sources associated with late positive evoked potentials during visual oddball task. AB - The present investigation was undertaken in order to utilize magnetoencephalography to locate generator sources, modeled as equivalent current point dipoles, that account for the well-established late positive electrical potentials commonly measured along the midline (Cz, Pz, Fz, and Oz) in response to rare or task-relevant stimuli and their simultaneously recorded magnetic field components. Two simultaneous but spatially distinct sources were present in all six subjects. One source in which the magnetic flux exited and reentered the brain over the right hemisphere was localized in deep structures under the temporal cortex in the vicinity of the right hippocampal formation. The other occurred in the vicinity of the primary visual cortex in the occipital area with magnetic flux entering and exiting over the posterior aspects of the subjects' heads. These data correspond to depth and surface electrode studies that have demonstrated multiple generator sources. PMID- 8490322 TI - Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging. AB - In pursuing our work on the organization of human visual cortex, we wanted to specify more accurately the position of the visual motion area (area V5) in relation to the sulcal and gyral pattern of the cerebral cortex. We also wanted to determine the intersubject variation of area V5 in terms of position and extent of blood flow change in it, in response to the same task. We therefore used positron emission tomography (PET) to determine the foci of relative cerebral blood flow increases produced when subjects viewed a moving checkerboard pattern, compared to viewing the same pattern when it was stationary. We coregistered the PET images from each subject with images of the same brain obtained by magnetic resonance imaging, thus relating the position of V5 in all 24 hemispheres examined to the individual gyral configuration of the same brains. This approach also enabled us to examine the extent to which results obtained by pooling the PET data from a small group of individuals (e.g., six), chosen at random, would be representative of a much larger sample in determining the mean location of V5 after transformation into Talairach coordinates. After stereotaxic transformation of each individual brain, we found that the position of area V5 can vary by as much as 27 mm in the left hemisphere and 18 mm in the right for the pixel with the highest significance for blood flow change. There is also an intersubject variability in blood flow change within it in response to the same visual task. V5 nevertheless bears a consistent relationship, within each brain, to the sulcal pattern of the occipital lobe. It is situated ventrolaterally, just posterior to the meeting point of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus. In position it corresponds almost precisely with Flechsig's Feld 16, one of the areas that he found to be myelinated at birth. PMID- 8490324 TI - Influence of isotonic, isometric and isokinetic muscle strength on bone mineral density of the spine and femur in young women. AB - Bone mineral density (BMD) is dependent on multiple influences including genetics, mechanical forces, hormonal changes and nutritional mechanisms. The mechanical forces are, in part, influenced by muscle strength. This study examined the relationships between BMD of the spine and femur with muscle strength. Eighty-one healthy, non-athletic women aged 20-30 years were the subjects in the study. BMD was measured by dual energy x-ray absorptiometry. Trunk strength was measured by a Wagner Dynamometer or a Cable Tensiometer and leg strength was measured with a Cybex II isokinetic dynamometer. Trunk, leg and hip strength was also measured using 1 RM (one repetition maximum). There were significant correlations between spine density and trunk extension (r = 0.40, P = 0.0001) and spine density and trunk flexion (r = 0.30, P = 0.0037). There were significant correlations between femoral neck density and knee extension (r = 0.40, P = 0.003) and femoral neck density and knee flexion (r = 0.24, P = 0.0240). Multiple regression analysis showed that amongst young adult females weight and trunk extensor muscle strength contributed about equally to spine density. Flexor muscle strength did not influence bone density. PMID- 8490323 TI - Dye-coupling in human neocortical tissue resected from children with intractable epilepsy. AB - Interneuronal communication mediated by gap junctions has been proposed to have an important role in brain development and in the genesis of epilepsy. Indirect evidence for the existence and function of gap junctions has been obtained by studying dye-coupling, the transfer of the low-molecular-weight fluorescent dye Lucifer yellow (LY), among neurons. In the present study, the incidence of dye coupling was assessed at different stages of human postnatal brain development. Pathological neocortical tissue was obtained from children from 3 to 172 months of age suffering from pediatric epilepsy and undergoing surgery to alleviate intractable seizures. Tissue samples were classified into least and most abnormal according to a number of diagnostic measures to ascertain if the incidence of dye coupling could be related to the degree of epileptogenicity of the sample. Regardless of the degree of abnormality, a significant developmental decrease in the incidence of dye-coupling was observed. In children 3-16 months, dye-coupling occurred in 38% of single intracellular injections of LY. From 32 to 83 months, the frequency of dye-coupling decreased to 13%. Finally, from 93 to 172 months, dye-coupling was observed in only 4% of injections. The frequency of dye-coupling between the least and most abnormal samples was not significantly different, although the frequency of dye-coupling was higher in the least abnormal samples from the youngest group (3-16 months). These findings underscore the role of gap junctions during brain development. However, they do not provide support, at least in vitro, for the hypothesis that gap junctions have an important role underlying epilepsy. PMID- 8490325 TI - Long-term cultivation of human osteoblasts. AB - Primary cultures of osteoblastic cells were obtained from human bone tissue after corrective surgery. Osteoblasts were isolated with a combined enzymatic and cell migration method and characterized by a high expression of alkaline phosphatase (AP), the marker enzyme for osteoblasts. For quantification of AP a new sensitive method has been developed. Also the secretion of osteocalcin measured by radioimmunoassay (RIA) which was stimulated by calcitriol, characterized isolated cells as osteoblasts. Osteoblasts isolated by the enzymatic and migration method formed 3-dimensional structures during cultivation in a mixed basal medium containing serum substitute, vitamin C and glycerophosphate. They maintained their specific cell characteristics over a period of 50 generations and did not dedifferentiate in contrast to their cultivation in medium containing fetal calf serum. Therefore a great amount of differentiated human osteoblasts could be obtained after cultivation of the primary cultures from different donors and this allows the examination of the influence of age and sex on cellular activity. PMID- 8490326 TI - The ultra long-term treatment of senile osteoporosis with 1 alpha-hydroxyvitamin D3. AB - We have attempted to examine the effects of long-term treatment with 1 alpha hydroxyvitamin D3 (1 alpha-OHD3; 0.5-1.0 microgram/day) on bone and chemical parameters in osteoporosis, retrospectively. Twenty-six pairs of age-, period of observation- and initial bone mineral density-matched patients with or without treatment were selected from 86 patients with osteoporosis. An 11% decrease ( 2.2%/year) and a 6% increase in radial mineral density at the peripheral cortical bone site was observed in the control and the treated group after 5 years, respectively (P < 0.05-0.01). There were no patients who showed hypercalcemia nor an abnormally high blood urea nitrogen (BUN) level in both groups. These results indicate that 1 alpha-OHD3 treatment in osteoporosis is effective and has no serious adverse effects. Although the facts were obtained from observations only at the peripheral cortical bone site, 1 alpha-OHD3 treatment may be considered as a potential mode of therapy for osteoporosis. PMID- 8490327 TI - Precision of dual energy x-ray absorptiometry in the upper extremities. AB - Dual energy x-ray absorptiometry (DEXA) has been shown to be a precise method for measuring bone mineral density (BMD) and content (BMC) in lumbar spine and proximal femur, but it has not been widely used in other skeletal sites. The in vivo day-to-day precision of DEXA (Norland XR-26) for seven anatomic sites in the upper extremities was evaluated by twice measuring both the right and left sides in ten subjects. For consistently defined regions-of-interest, the following precision values (coefficient of variation) were obtained for BMD and BMC: 0.8% and 1.0% (proximal humerus); 0.5% and 0.5% (humeral shaft); 0.7% and 0.5% (radial shaft); 1.3% and 1.1% (ulnar shaft); 0.7% and 1.0% (distal radius); 0.7% and 1.2% (distal ulna); 0.4% and 0.6% (hand). The initially observed relative side-to-side differences did not change significantly in the repeated measurements. Our results indicate that DEXA is a precise method for assessment of BMD and BMC also in the upper extremities. PMID- 8490328 TI - Lack of effect of nasal salmon calcitonin on cell-mediated immunity. AB - The calcium lowering hormone, calcitonin, also affects the immune system. The effect of nasal salmon calcitonin on lymphocyte transformation tests and on serum ionised calcium was investigated in a randomised, double-blind and placebo controlled study including 24 healthy adult volunteers. The participants received a single dose of either 200 IU of nasal salmon calcitonin or nasal placebo in the morning and measurements were done before and 3 h after administration of the spray. Nasal salmon calcitonin exerted a significant hypocalcemic effect, but did not interfere with antigen- or mitogen-induced expansion of T-lymphocytes. It is unlikely that nasal salmon calcitonin affects cell-mediated immunity in healthy subjects. PMID- 8490329 TI - Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat. AB - The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation. PMID- 8490330 TI - Protective effects of disodium etidronate and pamidronate against the biomechanical repercussion of betamethasone-induced osteopenia in growing rat femurs. AB - To assess the protective effect of bisphosphonates on the biomechanical repercussion of glucocorticoid-induced osteopenia, intraperitoneal doses of 1 or 10 mg/kg/d of disodium etidronate or 1 or 50 mg/kg/day of pamidronate were given to groups of 6 growing rats simultaneously receiving subcutaneous doses of 4.8 mg/kg/day of betamethasone for 20 days. Betamethasone impaired strength and stiffness of femur diaphyses through a reduction of geometric properties, abnormally enhancing bone ability to absorb energy. Both bisphosphonates partially prevented betamethasone effects on diaphyseal stiffness (but not strength) through positive, dose-related effects on material modulus of elasticity and slighter improvements in diaphyseal geometry, avoiding the enhancement of energy-absorbing ability and the subsequent tendency to production of comminute fractures. These results and others obtained treating normal rats with (pamidronate) APD suggest that the sign of bisphosphonate effects on bone biomechanics may depend not only on the type of compound but also on eventual interactions with concomitant treatments. PMID- 8490331 TI - Cardiac rehabilitation. PMID- 8490332 TI - Designer hips. PMID- 8490333 TI - Does Crohn's disease have a mycobacterial basis? PMID- 8490334 TI - Night visits in general practice. PMID- 8490335 TI - Role models and patronage. PMID- 8490336 TI - Career grade posts in NHS trusts. PMID- 8490337 TI - Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland, including the area near Dounreay nuclear site. AB - OBJECTIVE: To determine if any excess of childhood leukaemia and non-Hodgkin's lymphoma was associated with certain striking examples of population mixing in rural Scotland produced by the North Sea oil industry. DESIGN: Details were traced for over 30,000 workers involved in the construction of the large oil terminals in the Shetland and Orkney islands in northern Scotland or employed offshore. Home addresses of the 17,160 Scottish residents were postcoded, integrated with census data, and then classified as urban or rural. Rural postcode sectors, ranked by proportion of oil workers, were grouped into three categories with similar numbers of children but contrasting densities of oil workers. The incidence of leukaemia and non-Hodgkin's lymphoma was examined in these rural (and also in urban) categories in the periods 1974-8, 1979-83 and 1984-8. SETTING: Scotland. SUBJECTS: Young people below age 25. RESULTS: A significant excess of leukaemia and non-Hodgkin's lymphoma was found in 1979-83 in the group of rural home areas with the largest proportion of oil workers, following closely on large increases in the workforce. The area near the Dounreay nuclear installation, where an excess of leukaemia is already well known, was within the rural high oil category. CONCLUSION: The findings support the infection hypothesis that population mixing can increase the incidence of childhood leukaemia in rural areas. They also suggest that the recent excess in the Dounreay-Thurso area is due to population mixing linked to the oil industry, promoted by certain unusual local demographic factors. PMID- 8490338 TI - Spontaneous resolution of severe chronic glue ear in children and the effect of adenoidectomy, tonsillectomy, and insertion of ventilation tubes (grommets). AB - OBJECTIVE: To measure the time to spontaneous resolution of severe chronic otitis media with effusion (glue ear) in children and study the effects of adenoidectomy, adenotonsillectomy, and ventilation tubes (grommets). DESIGN: Randomised controlled study over 12 years. SETTING: Paediatric otorhinolaryngology clinics and in-patient unit. SUBJECTS: 228 children aged 2-9 years with pronounced hearing loss from glue ear and persistent bilateral middle ear effusions confirmed on three occasions over three months. INTERVENTIONS: Children were randomly allocated to adenotonsillectomy, adenoidectomy, or neither procedure. In all groups a Shepard type ventilation tube was inserted in one randomly chosen ear. Follow up was annually for five years and then less often for up to seven years four months. For analysis the two operated groups were combined. MAIN OUTCOME MEASURES: Otoscopic clearance of fluid, change in tympanogram, and improvement in mean audiometric hearing threshold. RESULTS: Survival analysis showed appreciable otoscopic and tympanometric resolution of fluid with ventilation tubes alone and adenoidectomy alone compared with no surgery. Further improvement was seen after combination of both treatments. Mean audiometric hearing thresholds improved with fluid resolution. Resolution was delayed in younger children and in those whose parents smoked, irrespective of treatment. Whereas a single insertion of a Shepard tube resolved the glue for a mean (SD) period of 9.5 (5.2) months, the effect of adenoidectomy was sustained throughout follow up. CONCLUSIONS: Treatment of glue ear considerably shortened the time to fluid resolution, combined adenoidectomy and tube insertion being better than either procedure alone. Resolution was longer in younger children and those whose parent(s) smoked, irrespective of treatment. PMID- 8490339 TI - Effect of influenza B virus infection on human performance. PMID- 8490340 TI - Visiting through the night. AB - OBJECTIVE: To describe the time distribution of visits at night and to evaluate trends in night visits from 1982 to 1992. DESIGN: Analysis of a sample of one in 12 claim forms for night visits submitted over one year beginning 1 July 1991, and estimation of the number of night visits in previous years from data on payment. Further information was obtained from performance indicators from the Department of Health. SETTING: General practices responsible to Berkshire family health services authority. MAIN OUTCOME MEASURES: Times of night visits, proportion performed by deputies, and trend in number of night visits after adjusting for the increased hours during which visits are claimed. RESULTS: The change in the hours for which payment may be claimed accounted for 33.8% (536/1584) of all night visits in the sample. After visits during these extra two hours were excluded, claims increased by 38.7% from 1989 to 1992 and more than doubled in the past 10 years. Use of deputies both in Berkshire and in England and Wales dropped by more than half since 1989. General practitioners in Berkshire claimed 31.5 night visits per 1000 population in 1992. CONCLUSIONS: The increase in the number of night visits is only partly due to the change in hours during which visits may be claimed. It is also due to a long term and possibly accelerating rise in demand. This is despite a major reduction in the proportion of calls performed by deputising services, the use of which had been said to be the main factor increasing the numbers of night visits. PMID- 8490342 TI - ABC of sleep disorders. Daytime sleepiness. PMID- 8490341 TI - Care management and mental health. AB - The community care reforms will produce a new kind of key worker who will organise and budget for packages of care: the care manager. Care management goes live in April 1993 but is still poorly rehearsed and its performance may yet disappoint. This overview sets out the origins of case management, its transformation into care management, and the principles guiding its practice. To spell out how the concept works, plans for care management in Southwark's mental health services are described. PMID- 8490343 TI - Acute bacterial meningitis in young adults mistaken for substance abuse. PMID- 8490344 TI - Guidelines for the management of asthma: a summary. British Thoracic Society and others. PMID- 8490345 TI - Tackling inequalities in health: the Australian experience. AB - Federal and state governments in Australia have embarked on a series of national initiatives which show a firm commitment to tackling social inequalities in health. The development of national goals and targets for health, for example, covers social and environmental conditions and sets differential targets for specific social groups with very poor health status. In a complementary initiative, a wide ranging analysis of the health care system--the National Health Strategy--has as one of its main objectives to improve the equitable impact of the health system. Where problems of access to and quality of services have been exposed, policies have been devised to deal with them. The exceptionally poor health of the Aboriginal community has elicited cross party support for action. Resources have been allocated to implement the National Aboriginal Health Strategy: to improve living and working conditions, education, and employment opportunities. Britain can glean much from the Australian experience. PMID- 8490346 TI - Ethical issues in randomised prevention trials. PMID- 8490347 TI - Ethical issues in randomised preventive trials. PMID- 8490348 TI - Microphthalmos and anophthalmos and environmental pollutants. PMID- 8490349 TI - Harvard's "new pathway". PMID- 8490350 TI - Sexually transmitted diseases and HIV infection among homosexual men. PMID- 8490351 TI - Sexually transmitted diseases and HIV infection among homosexual men. PMID- 8490352 TI - Sexually transmitted diseases and HIV infection among homosexual men. PMID- 8490353 TI - Paradoxical pain. PMID- 8490354 TI - Paradoxical pain. PMID- 8490355 TI - Paradoxical pain. PMID- 8490356 TI - Paradoxical pain. PMID- 8490357 TI - Neonatal group B streptococcal infections. PMID- 8490358 TI - Treating hypertension in elderly patients. PMID- 8490359 TI - Inherited prion disease. PMID- 8490360 TI - Inherited prion disease. PMID- 8490361 TI - Interpreting fluoroscein angiograms. PMID- 8490362 TI - The language of health. PMID- 8490363 TI - The language of health. PMID- 8490364 TI - The new deal in Trent. PMID- 8490365 TI - Costs of screening are important. PMID- 8490366 TI - Health services research. PMID- 8490368 TI - Juniors' new deal meets its first deadline. PMID- 8490367 TI - Institutional care and elderly people. PMID- 8490369 TI - Enhancing the educational content of SHO posts. PMID- 8490370 TI - Urinary incontinence in the community. PMID- 8490371 TI - Filtering white cells from blood for transfusion. PMID- 8490372 TI - Effects of prematurity and intrauterine growth on respiratory health and lung function in childhood. AB - OBJECTIVE: To determine whether birth weight and gestational age are associated with respiratory illness and lung function in children aged 5-11 years. DESIGN: Cross sectional analysis of parent reported birth weight, gestational age, and respiratory symptoms; parental smoking and social conditions; forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory rates between 25% and 75% and 75% and 85% (FEF25-75 and FEF75-85), and height. SETTING: Primary schools in England and Scotland in 1990. SUBJECTS: 5573 children aged 5-11 (63.3% of eligible children) had respiratory symptoms analysed and 2036 children (67.1% of eligible children) had lung function measured. MAIN OUTCOME MEASURES: Symptoms of asthma, bronchitis, occasional and frequent wheeze, cough first thing in the morning, and cough at any other time and lung function. RESULTS: Birth weight adjusted for gestational age was significantly associated with all lung function measurements, except FEF25-75. The association remained for FVC (b = 0.475, 95% confidence interval 0.181 to 0.769) and FEV1 (b = 0.502, 0.204 to 0.800) after adjustment for gestational age, parental smoking, and social factors. FEF75-85 was the only lung function related to gestational age. Respiratory symptoms, especially wheeze most days (adjusted odds ratio 0.9, 0.84 to 0.97) were significantly associated with prematurity. Every extra week of gestation reduced the risk of severe wheeze by about 10%. CONCLUSIONS: Lung function is affected mainly by intrauterine environment while respiratory illness, especially wheezing, in childhood is related to prematurity. PMID- 8490373 TI - An evaluation of the multidisciplinary approach to psychiatric diagnosis in elderly people. AB - OBJECTIVE: To determine the accuracy of psychiatric diagnoses made by two community psychogeriatric teams operating a multidisciplinary assessment procedure. DESIGN: Comparison of team diagnosis with independent formal assessment and consensus diagnosis by research psychiatrists. SETTING: Two community psychogeriatric teams with similar operational policies in an inner London health district. SUBJECTS: 100 people aged 65-90 (70 women) newly referred to the teams. MAIN OUTCOME MEASURES: Concordance between team and research diagnoses. RESULTS: Agreement between team and research diagnoses ranged from 90% to 99% for the specific psychiatric disorders studied. There was no significant difference between medical and non-medical team members in their diagnostic performance compared with the research psychiatrists. Increased diagnostic accuracy by team members was associated with longer experience of team working, regardless of the team members' professional background. CONCLUSIONS: The multidisciplinary approach to the assessment of referrals to these community teams for the elderly is not associated with misdiagnosis of psychiatric disorder. PMID- 8490374 TI - Evaluating perinatal mortality rates: effects of referral and case mix. AB - OBJECTIVE: To evaluate perinatal mortality rates as a method of auditing obstetric and neonatal care after account had been taken of transfer between hospitals during pregnancy and case mix. DESIGN: Case-control study of perinatal deaths. SETTING: Leicestershire health district. SUBJECTS: 1179 singleton perinatal deaths and their selected live born controls among 114,362 singleton births to women whose place of residence was Leicestershire during 1978-87. MAIN OUTCOME MEASURE: Crude perinatal mortality rates and rates adjusted for case mix. RESULTS: An estimated 11,701 of the 28,750 women booked for delivery in general practitioner maternity units were transferred to consultant units during their pregnancy. These 11,701 women had a high perinatal mortality rate (16.8/1000 deliveries). Perinatal mortality rates by place of booking showed little difference between general practitioner units (8.8/1000) and consultant units (9.3-11.7/1000). Perinatal mortality rates by place of delivery, however, showed substantial differences between general practitioner units (3.3/1000) and consultant units (9.4-12.6/1000) because of the selective referral of high risk women from general practitioner units to consultant units. Adjustment for risk factors made little difference to the rates except when the subset of deaths due to immaturity was adjusted for birth weight. CONCLUSION: Perinatal mortality rates should be adjusted for case mix and referral patterns to get a meaningful result. Even when this is done it is difficult to compare the effectiveness of hospital units with perinatal mortality rates because of the increasingly small subset of perinatal deaths that are amenable to medical intervention. PMID- 8490375 TI - Residential care for elderly people: a decade of change. AB - OBJECTIVE: To determine the changes between 1979 and 1990 in demography and dependency levels in elderly people in residential care. DESIGN: Censuses of those aged 65 years and over in any type of residential care at midnight on 11 December 1979 and 27 November 1990. SETTING: Leicestershire District Health Authority (population 865,133, 1991 census), coterminous with county and social services boundaries. MAIN OUTCOME MEASURES: Age, sex, length of stay, and dependency levels (measured by activities of daily living). RESULTS: In 1990 (1979), 6079 (4678) elderly people were enumerated in 241 (133) establishments, a 30% increase in the numbers of elderly people in residential care and an 82% increase in the number of establishments between 1979 and 1990. Dependency levels rose between 1979 and 1990 in all but the geriatric sector, the greatest increases being found in private residential homes where the largest percentage increase in the number of residents had occurred. CONCLUSIONS: Dependency levels in residential care have risen substantially, particularly in the private sector, even beyond levels expected from the greater numbers of elderly people. With the impending move to community care, dependency levels are likely to rise further, and more appropriate staff training and medical input to homes will become necessary. PMID- 8490376 TI - Leukaemia linked to eating disorders. PMID- 8490377 TI - Urinary incontinence in the community--analysis of a MORI poll. AB - OBJECTIVES: To investigate the prevalence of urinary incontinence among people living at home, their responses to it, and its emotional and social effects. DESIGN: Random sample of 4007 adults interviewed in their own homes. SETTING: Random sample of 178 constituency sampling points throughout Great Britain. SUBJECTS: 1883 men, 2124 women aged 30 and over. MAIN OUTCOME MEASURES: Responses to questionnaire. RESULTS: 6.6% (125) men and 14.0% (297) women had been incontinent of urine at some time--2.8% (52) men and 7.5% (159) women in the previous two months and 61% (124) of these for more than four years. 52% (108) had consulted their general practitioner at the onset of incontinence and a further 31% (65) later. Doctors commonly took a urine sample (163, 54%), referred the patient to a specialist (127, 42%), and prescribed tablets (109, 36%); only 22% (66) carried out an abdominal, rectal, or vaginal examination. Patients were not embarrassed in seeing their doctor and most thought they were treated sympathetically. 60% (265) of all those affected were concerned or worried about their incontinence, and in almost half incontinence limited their daily social activities. CONCLUSION: More people with incontinence seem to be consulting their doctors about it than has been found in previous studies, but the procedures carried out by general practitioners still seem to be suboptimal. Urinary incontinence has a profound effect on the day to day lives of most of those who suffer from it. PMID- 8490378 TI - Is routine induction of labour at term ever justified? AB - Balancing the risks of prolonged gestation against those of induced labour is difficult. Risks to the fetus increase slightly after 42 weeks' gestation but women having labour induced are more likely to have instrumental deliveries or babies with low Apgar scores. Since many women are now expressing a preference for minimal interference in childbirth the most acceptable management of post term pregnancy seems to be increased fetal surveillance. Each case needs to be considered individually and it is important that the woman is involved in the decision to induce. PMID- 8490379 TI - Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. PMID- 8490380 TI - ABC of sleep disorders. "I don't get enough sleep, doctor". PMID- 8490381 TI - Long term care on the NHS: a vanishing prospect. PMID- 8490382 TI - Mental health services--the user's view. AB - The needs of people with serious mental illnesses have dominated much of the debate on reforming community care. In this article Peter Campbell, who has used mental health services many times in the past, explains how the reforms could affect people like him. He welcomes the thinking behind the changes, particularly the idea that people who use community care should take part in planning services, but he warns that implementing the new philosophy might prove very difficult. Mr Campbell is secretary of a voluntary organisation for users of mental health services called Survivors Speak Out. The views he expresses here are his own, and do not necessarily reflect those of Survivors Speak Out. PMID- 8490383 TI - Racial discrimination against doctors. PMID- 8490384 TI - Racial discrimination against doctors. PMID- 8490385 TI - Death rate from asthma. PMID- 8490386 TI - Death rate from asthma. PMID- 8490387 TI - Screening for prostatic cancer. PMID- 8490388 TI - Screening for prostatic cancer. PMID- 8490389 TI - Dangers of long waiting times. PMID- 8490390 TI - Screening for prostatic cancer. PMID- 8490391 TI - Reducing waiting lists requires more staff. PMID- 8490392 TI - Waiting time for first outpatient appointment. PMID- 8490393 TI - Preventing congenital abnormalities. PMID- 8490394 TI - Publicity and infants' sleeping position. PMID- 8490395 TI - Screening for diabetes during pregnancy. PMID- 8490396 TI - Mothers' consent to screening newborn babies for disease. PMID- 8490397 TI - Medical management of Duchenne muscular dystrophy. PMID- 8490398 TI - Working with adult survivors of child sexual abuse. PMID- 8490399 TI - Screening for hypertrophic cardiomyopathy. PMID- 8490400 TI - Community dermatology. PMID- 8490401 TI - Screening for hypertrophic cardiomyopathy. PMID- 8490402 TI - Community dermatology. PMID- 8490403 TI - Academic obstetrics and gynecology. PMID- 8490404 TI - Continuing education needed for forensic medical examiners. PMID- 8490405 TI - Male obstetricians and their patients. PMID- 8490406 TI - Commissioning specialist services. PMID- 8490407 TI - An old problem solved in child care. PMID- 8490408 TI - Dural puncture and headache. PMID- 8490409 TI - Managing miscarriage medically. PMID- 8490410 TI - Accidental dural puncture in obstetric patients and long term symptoms. AB - OBJECTIVE: To examine the association between accidental dural puncture and long term headache and related symptoms. DESIGN: Postal questionnaire survey to elucidate new symptoms occurring after childbirth, and linking of these to data in obstetric and anaesthetic case notes. Women were surveyed between 13 months and nine years after delivery. SETTING: Birmingham Maternity Hospital. SUBJECTS: 4700 women who had delivered their most recent baby under epidural anaesthesia, 74 of whom had suffered an accidental dural puncture. MAIN OUTCOME MEASURES: Frequencies of new headache or migraine or neck ache starting within three months after childbirth and lasting over six weeks. RESULTS: Among the 74 women who had had an accidental dural puncture there were 17 (23%) who reported one or more of the above symptoms. By comparison, among those who had had an epidural anaesthetic but no recorded puncture, only 329 (7.1%) reported these symptoms. The duration of the headache or migraine or neck ache in the dural tap group ranged from nine weeks to over eight years. Ten of these women reported still unresolved symptoms. CONCLUSIONS: Conclusions on causality were tentative. Most women would remember a dural tap, and this might influence their reporting of subsequent symptoms attributable to the event. In addition, detailed characterisation of the symptoms was not available. Nevertheless, the findings provide a clear indication of the need for further study of the possible long term sequelae of accidental dural puncture. PMID- 8490411 TI - Factors affecting quality of informed consent. AB - OBJECTIVE: To examine the factors influencing quality of informed consent. DESIGN: Prospective study comprising interviews with patients and patients' completing standard questionnaires. SETTING: Academic surgical unit of large teaching hospital. PATIENTS: 265 patients undergoing intrathoracic, intraperitoneal, and vascular surgical procedures. Of these patients, 192 have been followed up for six months. MAIN OUTCOME MEASURES: Patients' recall of information at various points in the study; this score was compared by age, provision of written information, cognitive function, intelligence quotient (IQ), mood state and personality traits, and health locus of control. RESULTS: The patients were best informed immediately after signing the consent form and from then on recall of information deteriorated. A total of 172/250 (69%) patients admitted to not reading the consent form before signing it. Old age adversely affected recall of information at all assessment points. Impaired cognitive function reduced information recall only during the stay in hospital. Patients with above average IQs handled information better than those with a lower IQ except immediately after the signing of consent forms. Patients with an internal locus of health control (that is, those who believed their health to be in their own control) were better informed than those with an external locus of health control. Operation information cards improved recall only on the day of discharge. CONCLUSION: Elderly patients and patients with below average IQ, impaired cognitive functions, and an external locus of control have poor information recall. Written information may be more useful if given before admission to hospital. PMID- 8490412 TI - Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer. AB - OBJECTIVE: To determine whether prolonged infection with hepatitis B virus is associated with a lower blood cholesterol concentration. DESIGN: Cross sectional study. SETTING: 81 villages in rural China with a high prevalence of chronic infection with hepatitis B virus. SUBJECTS: 1556 apparently healthy men aged 35 64 years, randomly selected. MAIN OUTCOME MEASURES: Hepatitis B virus carrier state; plasma concentrations of cholesterol, apolipoprotein B, and apolipoprotein A I. RESULTS: 238 (15%) of the men were positive for hepatitis B surface antigen, indicating that they were chronic carriers. Plasma concentration of cholesterol was 4.2% (0.11 mmol/l) lower among carriers (that is, positive for hepatitis B surface antigen) than among non-carriers (95% confidence interval 0.6% to 8.0% (0.01 to 0.21 mmol/l), p < 0.05), and apolipoprotein B concentration was 7.0% (0.036 g/l) lower (2.8% to 11.2% (0.014 to 0.058 g/l), p < 0.001). In contrast, no association was observed between plasma concentrations of cholesterol or apolipoprotein and hepatitis B that had been eradicated (that is, patient positive for hepatitis B core antibody but negative for hepatitis B surface antigen). CONCLUSIONS: Chronic hepatitis B virus infection, which usually starts in early childhood in China, seems to lead not only to a greatly increased risk of death from liver disease but also to a somewhat lower cholesterol concentration in adulthood. This common cause produces an inverse association between cholesterol concentration and risk of death from liver cancer or from other chronic liver diseases. PMID- 8490413 TI - Medical management of miscarriage: non-surgical uterine evacuation of incomplete and inevitable spontaneous abortion. PMID- 8490414 TI - Severity of inflammation of tympanic membrane as predictor of clinical course of recurrent acute otitis media. PMID- 8490415 TI - Benylin (dextromethorphan) abuse and mania. PMID- 8490416 TI - Hypercalcaemia associated with calcipotriol (Dovonex) treatment. PMID- 8490417 TI - Interstitial pneumonitis and interferon-alfa. PMID- 8490418 TI - Low back pain associated with anistreplase. PMID- 8490419 TI - Developing a register of randomised controlled trials in primary care. AB - OBJECTIVE: To determine the number, nature, site of publication, and feasibility of identifying randomised controlled trials relevant to primary care. DESIGN: Review of literature using three strategies: approaching journal editors, Medline search, and manual search of individual journals. SETTING: Journals containing publications of studies based in primary care. MAIN OUTCOME MEASURES: The number, site of publication, and subject of trials identified. RESULTS: No journal had a system which enabled identification of all the randomised controlled trials it published. 266 trials relevant to primary care were identified from 110 different journals during 1987-91 by Medline. Of these, only 62 trials were published in primary care journals. Hand searching of seven major primary care research journals showed that between 13% and 38% of the trials had been missed by the Medline search. Of the trials identified, 47 (18%) were concerned with mental disease (including neuroses, tobacco misuse and alcohol misuse) and 43 (16%) were concerned with hypertension. CONCLUSION: Given the diversity of publication sources and topics, this supports the need for a centrally based register of randomised controlled trials that may be relevant to primary care overviews in the future. PMID- 8490420 TI - Personalia and the current health crisis. AB - Recent changes in the Russian government introduced by Boris Yeltsin include the appointment of Eduard Nechaev as health minister at the beginning of this year. The appointment received little publicity in the West, although his predecessor was sacked after only one year for failing to make any effort to improve health care. The challenges facing the new minister are enormous. Not only does he have to introduce a new medical insurance system but he has to tackle the problems of falling population, rising childhood illness linked to poor diet, and the spread of polio and diphtheria. It remains to be seen whether his experience in the military medical service has equipped him for the job. PMID- 8490421 TI - Lessons from Lithuania: rethinking public health training. AB - Lithuania faces stark problems that are familiar to most countries in the former Soviet Union: high morbidity and mortality rates, pollution, an unstable economy, and rapid changes in the financing and organisation of health care. In this environment Moore and Dixon visited Kaunas Medical Academy to help identify how training in public health medicine could contribute towards improving the health of the population. Although over 200 hours are devoted to public health training for medical undergraduates, teaching is unfocused, fragmented, and includes little epidemiology--the core subject for public health physicians. Teaching is mainly through long lectures with few group discussions. Student participation and motivation are low. As well as recommending redesign of the curriculum, Moore and Dixon suggested training in teaching methods for teachers. They also suggested that postgraduate training in public health should begin and should be targeted at hospital managers, teaching staff, and existing public health physicians. PMID- 8490422 TI - Advice to a Moscow children's hospital. AB - At the request of the largest children's hospital in Moscow, McKenzie and colleagues made recommendations for improving the service. Restrictions on visiting and fears of contracting illness from non-disposable needles have discouraged the local population from using the hospital. Consequently the hospital is underused and overstaffed. Serious shortages of drugs and surgical supplies compromise care. Fundamental changes are needed in nursing and postgraduate education. The authors encouraged their Russian colleagues to address the health care needs of their local population and to develop family centred care, and they offered training in London. PMID- 8490423 TI - Headache after dural puncture. PMID- 8490424 TI - Old people's homes: the relatives' view. AB - On 1 April new arrangements came into force for arranging and funding residential care for elderly people in Britain. From now on those who seem to need full time care will be assessed first by care managers employed by local authority social services departments. This may lead to admission to an old people's home or a nursing home. Local authorities have been told to consult both users and carers about such decisions. But what about relatives who have not actually been giving care directly? The Relatives Association was set up last year as a voluntary organisation for the relatives and friends of older people living in residential homes. Below, its vice president, Mavis Nicholson, a journalist and broadcaster whose mother died of Alzheimer's disease in a residential home last year, gives her personal view of being such a relative. And Dorothy White, the association's founder, explains what the future may hold for elderly residents and their relatives. PMID- 8490425 TI - ABC of sleep disorders. Parasomnias. PMID- 8490426 TI - ACE inhibitors after myocardial infarction. PMID- 8490427 TI - ACE inhibitors after myocardial infarction. PMID- 8490428 TI - Cardiovascular disease in developing countries. PMID- 8490429 TI - Informed consent. PMID- 8490430 TI - Informed consent. PMID- 8490431 TI - Informed consent. PMID- 8490432 TI - Informed consent. PMID- 8490433 TI - Informed consent. PMID- 8490434 TI - Informed consent. PMID- 8490435 TI - Consent for surgery for psychiatric patients. PMID- 8490436 TI - Population mixing and excess of childhood leukemia. PMID- 8490437 TI - Epidemiology of endometriosis. PMID- 8490438 TI - Epidemiology of endometriosis. PMID- 8490439 TI - Increasing patients' knowledge of secondary contraception. PMID- 8490440 TI - Re-emergence of tuberculosis. PMID- 8490441 TI - Re-emergence of tuberculosis. PMID- 8490442 TI - Re-emergence of tuberculosis. PMID- 8490443 TI - HIV and AIDS in health care workers. PMID- 8490444 TI - HIV and AIDS in health care workers. PMID- 8490445 TI - The thrifty genotype and non-insulin dependent diabetes. PMID- 8490446 TI - The thrifty genotype and non-insulin dependent diabetes. PMID- 8490447 TI - Persistent vegetative state. PMID- 8490448 TI - The thrifty genotype and non-insulin dependent diabetes. PMID- 8490449 TI - Waiting for plastic surgery. PMID- 8490450 TI - Waiting for plastic surgery. PMID- 8490451 TI - Tomlinson and the BMA. PMID- 8490452 TI - Diabetic patients' eyes must be examined. PMID- 8490453 TI - Listening to patients. PMID- 8490454 TI - Listening to patients. PMID- 8490455 TI - Drug smuggler's delirium. PMID- 8490456 TI - Drug smuggler's delirium. PMID- 8490457 TI - Measuring the outcome of perinatal care. PMID- 8490458 TI - Fundholding. PMID- 8490459 TI - Treating bed wetting. PMID- 8490460 TI - NHS rationing. PMID- 8490461 TI - Use of Indian ethnic remedies. PMID- 8490462 TI - Productivity in clinical medicine. PMID- 8490463 TI - Mitral valve prolapse. PMID- 8490464 TI - What social workers need. PMID- 8490465 TI - 1966 revisited: bright new contract or brave old world? PMID- 8490466 TI - Where are we now with vaccines against AIDS? PMID- 8490467 TI - HIV is active even in latency, say scientists. PMID- 8490468 TI - Doubt cast on zidovudine's use in delaying AIDS. PMID- 8490469 TI - Cerebral herniation during bacterial meningitis in children. AB - OBJECTIVE: To see whether the incidence of cerebral herniation is increased immediately after lumbar puncture in children with bacterial meningitis and whether any children with herniation have normal results on cranial computed tomography. DESIGN: Retrospective review of case notes; computed tomograms were read again. SETTING: Large paediatric teaching hospital. SUBJECTS: 445 children over 30 days old admitted to hospital with bacterial meningitis. MAIN OUTCOME MEASURES: Timing of herniation in relation to lumbar puncture; findings on computed tomography in children with herniation. RESULTS: Cerebral herniation was detected in 19 (4.3%) of the 445 children (21 episodes; herniation occurred twice in two children). Herniation occurred in 14 (45%) of the 31 children who died. Nineteen episodes of herniation occurred in the 17 children who had a lumbar puncture; 12 of the episodes occurred in the first 12 hours after the lumbar puncture and seven over six other 12 hour periods (odds ratio 32.6 (95% confidence interval 8.5 to 117.3); p < 0.001). The results of cranial computed tomography were normal in five (36%) of the 14 episodes of herniation in which scanning was performed at about the time of herniation. CONCLUSIONS: The temporal relation between lumbar puncture and herniation strongly suggests that a lumbar puncture may cause herniation in some patients, and normal results on computed tomography do not mean that it is safe to do a lumbar puncture in a child with bacterial meningitis. PMID- 8490470 TI - Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study. AB - OBJECTIVE: To assess the risk of cerebral thromboembolism in women using low dose oral contraceptives. DESIGN: A retrospective case-control study. SETTING: All Danish medical, neurological, neurosurgical, and gynaecological departments. SUBJECTS: All 794 women in Denmark aged 15-44 who had suffered a cerebral thromboembolic attack during 1985-9 and 1588 age matched randomly selected controls. RESULTS: Of 692/1584 case/control questionnaires sent out, 590/1396 (85.3%/88.1%) were returned. Among the cases, 15 refused to participate, 69 had a revised or unreliable diagnosis, 40 had had thromboembolic disease previously, 13 were pregnant, and 152 had a disease predisposing to a cerebral thromboembolic attack. Of the 323 cases without a known predisposition, 320 reported use or non use of oral contraception. Among the 1396 controls, eight refused to participate, were mentally retarded, or lived abroad; 18 returned an uncompleted questionnaire; 17 had had thromboembolic disease previously; 31 were pregnant; and 130 had a disease predisposing to a cerebral thromboembolic attack. Thus 1198 non-predisposed controls were available, among whom 1197 reported use or non-use of oral contraception. Among the 320 cases, 116 (36.3%) were oral contraceptive users at the time of the cerebral thromboembolic attack. By comparison there were 191 users (16.0%) among the 1197 controls, giving a crude odds ratio of 3.0. After multivariate analysis, including confounder control for age, smoking, years of schooling, and trend in use of different types of oral contraceptives during 1985-90, pills containing 50 micrograms oestrogen were associated with an odds ratio for cerebral thromboembolic attack of 2.9 (95% confidence interval 1.6 to 5.4), those containing 30-40 micrograms oestrogen an odds ratio of 1.8 (1.1 to 2.9), those containing progestogen only an odds ratio of 0.9 (0.4 to 2.4). The odds ratio did not change with increasing age or with duration of oral contraceptive use. A 50% increased risk of a cerebral thromboembolic attacks among cigarette smokers (after confounder control) was independent of oral contraception status and age. CONCLUSION: Low dose oral contraceptives are associated with an increased risk of cerebral thromboembolic attack. Combined or sequential pills containing 30-40 micrograms oestrogen are associated with a one third reduced risk compared with preparations containing 50 micrograms oestrogen. Progestogen only pills did not increase the risk of a cerebral thromboembolic attack. PMID- 8490471 TI - Effect of stress management on blood pressure in mild primary hypertension. AB - OBJECTIVE: To establish whether stress management had a larger effect than a control treatment on resting blood pressure, ambulatory blood pressure, and left ventricular mass. DESIGN: A 12 week baseline period of habituation to measurement of blood pressure was followed by randomisation to either stress management or mild exercise for six months and follow up six months later. SETTING: General practice, district general hospital, and medical school. PATIENTS: Of the 184 patients aged under 60 with mild primary hypertension who entered the baseline habituation period, 88 were excluded because they failed to meet the entry criteria or they withdrew from the study. The remaining 46 men and 50 women underwent treatment. INTERVENTIONS: 10 clinical sessions and daily practice at home of either stress management based on relaxation or non-aerobic stretching exercises. Mildly stressful 15 minute interviews before and after treatment. MAIN OUTCOME MEASURES: Diastolic and systolic blood pressure in the clinic and during 12 hours of ambulatory recording, and left ventricular mass measured by echocardiography. RESULTS: The patients' blood pressure fell during habituation (systolic pressure from 152 mmHg to 140 mmHg, diastolic pressure from 98 to 93 mm Hg), but neither resting nor ambulatory blood pressure was changed by the treatments. Left ventricular mass was also unchanged. Blood pressure rose during the stressful interview, but this rise was reduced by stress management (systolic pressure rose by 7.4 mmHg before treatment and by 3.7 mmHg after treatment). CONCLUSION: Stress management of a type advocated for treating mild primary hypertension is ineffective in lowering blood pressure in patients who are well habituated to measuring blood pressure. PMID- 8490472 TI - Rationale for stopping cervical screening in women over 50. AB - OBJECTIVE: To investigate whether the currently recommended age at which to stop cervical screening (64) can be lowered and what criteria should be used for safely doing so. DESIGN: Retrospective case analysis study. SETTING: Dundee and Angus districts of Scotland. SUBJECTS: Women diagnosed as having cervical intraepithelial neoplasia and microinvasive or invasive cancer of the cervix in 1989 and 1990 (798 cases). MAIN OUTCOME MEASURE: History of cervical cytology results according to age (age groups of five years) and screening interval (three years and five years). RESULTS: Cervical intraepithelial neoplasia was most common in women under 45 (711 cases in women of 45 and under v 38 cases in those of 46 and over). Cervical intraepithelial neoplasia occurring de novo was not seen in women over 50 who had been screened every three years. Microinvasive or invasive cancer of the cervix was diagnosed in 26 women over 50. None of these women had participated adequately in the cervical screening programme. CONCLUSION: Cervical intraepithelial neoplasia typically occurs in younger women. All women over 50 with an adequate history of negative results on smear testing every three years may be safely discharged from further screening if these findings are confirmed in other populations. PMID- 8490473 TI - Antibody persistence after accelerated immunisation against Haemophilus influenzae type b. PMID- 8490474 TI - Clinical coding: completeness and accuracy when doctors take it on. PMID- 8490475 TI - A new skin lesion associated with intravenous streptokinase. PMID- 8490476 TI - Acute renal failure during interferon treatment. PMID- 8490477 TI - Hypersensitivity vasculitis related to nicoumalone. PMID- 8490478 TI - Immunisation against influenza among people aged over 65 living at home in Leicestershire during winter 1991-2. AB - OBJECTIVES: To assess the size of the elderly population for whom influenza vaccine is indicated and how many are vaccinated. DESIGN: Cohort questionnaire study. SETTING: Leicestershire general practices. SUBJECTS: 800 elderly subjects selected a random from the Leicestershire family health services authority list who were not living in residential care, 565 of whom returned a questionnaire. MAIN OUTCOME MEASURES: Patient profile, vaccine offers, vaccination status, and reasons for not accepting vaccine. RESULTS: 170 of 334 (51%) people aged 65-74 years and 106 of 205 (52%) aged > or = 75 years had one or more medical indications for influenza vaccine. 195 people were offered vaccine, 49 of whom had no risk factor. 152 offers were made opportunistically during visits to the practice and only six were made in writing or by telephone. Overall 113 of 266 patients with known medical indications were immunised. Vaccine was accepted by 148 of 189 (78%) offered it, and, as judged by acceptance in sequential years, influenza vaccine was well tolerated. The main reasons for not being vaccinated were misconception about risk status and inadequate advice from doctors. CONCLUSIONS: The prevalence of medical indications for vaccine is not large enough to justify a policy of universal immunisation. Most patients offered vaccine accept it and tolerate it well. Improved targeting and education is needed to increase immunisation of people at risk. PMID- 8490479 TI - The Royal College of General Practitioners revisited. PMID- 8490480 TI - Is London overbedded? AB - OBJECTIVE: To examine whether there are too many hospital beds in London. DESIGN: Analysis of data from the Hospital In-Patient Enquiry, Mental Health Enquiry, health service indicators, and Emergency Bed Service. SETTING: England, London, and inner London. RESULTS: Hospital admission rates for acute plus geriatric services for London residents were very similar to the national values in all age groups. In the special case considered in the Tomlinson report--acute services in inner London--the admission rate was 22% above the value for England. However, the admission rate of inner deprived Londoners was 9% below that of comparable areas outside London. For psychiatry, admission rates in London roughly equalled those in comparable areas. When special health authorities were excluded, in 1990 1 there were 4% more acute plus geriatric beds available per resident in London than in England. Bed provision has been reduced more rapidly in London than nationally. Extrapolating the trend of bed closures forward indicates that beds (all and acute) per resident in London are now at about the national average. Data from the Emergency Bed Service indicate that the pressure on available hospital beds in London has been increasing since 1985. CONCLUSIONS: Data regarding bed provision and utilisation for all specialties by London residents do not provide a case for reducing the total hospital bed stock in London at a rate faster than elsewhere. Bed closures should take account of London's relatively poorer social and primary health care circumstances, longer hospital waiting lists, poorer provision of residential homes, and evidence from the Emergency Bed Service of increasing pressure on beds. Higher average costs in London, some unavoidable, are forcing hospital beds to be closed at a faster rate in London than nationally. PMID- 8490481 TI - Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society. AB - Several important new issues have arisen in the management of patients with hypertension. A working party of the British Hypertension Society has therefore reviewed available intervention studies on anti-hypertensive treatment and made recommendations on blood pressure thresholds for intervention, on non pharmacological and pharmacological treatments, and on treatment goals. This report also provides guidelines on blood pressure measurement, essential investigations, referrals for specialist advice, follow up, and stopping treatment. PMID- 8490482 TI - Is the money following the clients with learning disabilities? AB - For the past decade patients with learning disabilities living in long stay mental handicap hospitals have been resettled in the community. Local authorities have also taken on the care of new patients who would once have been long stay residents. The imperfect data that are available suggest that in England about half the residents in mental handicap hospitals in 1981 are now the responsibility of local authorities; the figures for Wales and Northern Ireland are 38% and 33%. Data on revenue suggest that the savings to the health service are much less--perhaps 9% in Northern Ireland and 3.6% in England, although there have also been capital gains through the sale of hospitals. Existing methods of transferring money from health to local authorities--joint finance and "dowries" for individual patients--do not seem adequately to have compensated local authorities. Moreover, as patients still to be transferred are more severely disabled local authorities will require larger sums--about 26 000 pounds per patient per year plus 39 200 pounds in capital. If the government chooses not to transfer these resources from health authorities it will be switching funds away from learning disabled people to other care groups. PMID- 8490483 TI - Helping disabled people--the user's view. AB - The main needs for most people with physical disabilities are housing and help with daily living. Thus, many of them will find the new emphasis on social aspects of community care particularly relevant. Peter Swain is a disabled man who leads a project in east Devon which ensures that disabled people have a voice in helping to shape the services they need. In this article he explains how the project, Living Options East Devon, works and how the new legislation for community care might affect disabled people. PMID- 8490484 TI - ABC of sleep disorder. Dreams and medical illness. PMID- 8490485 TI - Contamination of urine and faecal specimens. PMID- 8490486 TI - Treating hypoglycaemia in general practice. PMID- 8490487 TI - Treating hypoglycaemia in general practice. PMID- 8490488 TI - Tobacco and health education. PMID- 8490489 TI - Sudden infant death syndrome. PMID- 8490490 TI - Revised guidelines for HIV infected health care workers. PMID- 8490491 TI - Improving the management of superficial bladder cancer. PMID- 8490492 TI - What's happening to health care in Germany? PMID- 8490493 TI - Reporting deaths to coroners. PMID- 8490495 TI - Eastern Europe hopes to prevent AIDS epidemic. PMID- 8490494 TI - Revised guidelines for HIV infected health workers. PMID- 8490496 TI - Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging. AB - OBJECTIVE: To assess the value of transvaginal ultrasonography with colour blood flow imaging in detecting early ovarian cancer in women with a family history of the disease. DESIGN: Study of self referred symptomless women with a close relative who had developed the disease. Each woman was screened to detect persistent lesions and defined changes in ovarian volume. Morphological score and pulsatility index were recorded. SETTING: Ovarian screening clinic. SUBJECTS: 1601 self referred women. INTERVENTIONS: Women with a positive screening result were recommended to have further investigations. MAIN OUTCOME MEASURES: Findings at surgery and histology of abnormal ovaries. Morphological score > or = 5 and pulsatility index < 1.0 at last scan. RESULTS: Women were aged 17 to 79 (mean 47) years; 959 (60%) were premenopausal, 469 (29%) were naturally postmenopausal, and 173 (11%) had had a hysterectomy. 157 women had a pedigree suggestive of the site specific ovarian cancer syndrome and 288 of multiple site cancers. 61 women had a positive screening result (3.8%, 95% confidence interval 2.9 to 4.9%), six of whom had primary ovarian cancer detected at surgery (five stage Ia, one stage III). Use of a high morphological score or a low pulsatility index increased the odds of finding ovarian cancer from 1:9 to about 2:5 (1:1 in the highest risk groups). Five interval cancers were reported (three ovarian and two peritoneal). Eight of the 11 cancers developed in women with pedigrees suggestive of inherited cancer. CONCLUSIONS: Transvaginal ultrasonography with colour flow imaging can effectively detect early ovarian cancer in women with a family history of the disease. The screening interval should be less than two years. PMID- 8490498 TI - Clinicians and the coronial system: ability of clinicians to recognise reportable deaths. AB - OBJECTIVE: To assess the ability of clinicians to recognise deaths which require referral to the coroner. DESIGN: Postal questionnaire consisting of 16 fictitious case histories, 14 of which contained a clear indication for referral to the coroner. SETTING: Large teaching hospital. Coroner's office. SUBJECTS: 200 clinicians from general medical and surgical firms and senior staff of the local coroner's office (two coroner's officers and the two deputy coroners). MAIN OUTCOME MEASURES: Number of correct assessments on questionnaire. RESULTS: The mean recognition score for the clinicians was 9.11 (range 3-14) with no difference between the clinical grades. All of the coroner's senior staff recorded maximum recognition scores of 16. CONCLUSIONS: The study highlights several features of the coronial system which are poorly understood by clinicians and provides the basis for an initiative to improve the medicolegal education of all clinicians. PMID- 8490497 TI - Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. AB - OBJECTIVE: To assess the performance of the sequential combination of serum CA 125 measurement and ultrasonography in screening for ovarian cancer. DESIGN: The serum CA 125 concentration of each subject was determined and those with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. If ultrasonography gave abnormal results surgical investigation was arranged. Volunteers were followed up by annual postal questionnaire. SETTING: General practice, occupational health departments, ovarian cancer screening clinic. SUBJECTS: 22,000 women volunteers who were postmenopausal and aged over 45 years. MAIN OUTCOME MEASURES: Apparent sensitivity, specificity, positive predictive value, years of cancer detected. RESULTS: 41 women had a positive screening result and were investigated surgically. 11 had ovarian cancer (true positive result) and 30 had other disorders or no abnormality (false positive result). Of the 21,959 volunteers with a negative screening result, eight subsequently presented clinically with ovarian cancer (false negative result) and 21,951 had not developed ovarian cancer during follow up (apparent true negative result). The screening protocol achieved a specificity of 99.9%, a positive predictive value of 26.8%, and an apparent sensitivity of 78.6% and 57.9% at one year and two year follow up respectively. The estimated number of years of cancer detected by the prevalence screen was 1.4 years. CONCLUSIONS: This screening protocol is highly specific for ovarian cancer and can detect a substantial proportion of cases at a preclinical stage. Further investigation is required to determine the effect of the screening protocol on the ratio of early to late stage disease detected and on mortality from ovarian cancer. PMID- 8490499 TI - Pre-employment chest radiography for health service staff: who needs it? PMID- 8490500 TI - Litter and medical waste on bathing beaches in England and Wales. PMID- 8490501 TI - An instrument for assessment of videotapes of general practitioners' performance. AB - OBJECTIVES: To identify those important characteristics of doctors' and patients' behaviour that distinguish between "good" and "bad" consultations when viewed on videotape; to use these characteristics to develop a reliable instrument for assessing general practitioners' performance in their own consultations. DESIGN: Questionnaires completed by patients, general practitioner trainers, and general practitioner trainees. Reliability of draft instrument tested by general practitioner trainers. SETTING: All vocational training schemes for general practice in the Northern region of England. SUBJECTS: First stage: 76 patients in seven groups, 108 general practice trainers in 12 groups, and 122 general practice trainees in 10 groups. Second stage: 85 general practice trainers in 12 groups. MAIN OUTCOME MEASURES: Trainers' ratings of importance; alpha coefficients of draft instrument by trainee, group, and consultation. RESULTS: 6890 characteristics of good and bad consultations were consolidated into a draft assessment instrument consisting of 46 pairs of definitions separated by six point bipolar scales. Nine statement pairs given low importance ratings by trainers were eliminated, reducing the instrument to 37 statement pairs. To test reliability, general practitioner trainers used the instrument to assess three consultations. With the exception of one group of trainers, all alpha coefficients exceeded the acceptable level of 0.80. CONCLUSION: The instrument produced is reliable for assessing general practitioners' performance in their own consultations. PMID- 8490502 TI - Refusing to treat smokers is unethical and a dangerous precedent. PMID- 8490503 TI - Should smokers be offered coronary bypass surgery? Human frailty should not be penalised. PMID- 8490504 TI - Should smokers be offered coronary bypass surgery? Let the health authority take the responsibility. PMID- 8490505 TI - British National Formulary: its birth, death, and rebirth. AB - The British National Formulary is a direct descendant of the National War Formulary, in which the titles of the preparations were in Latin and the doses in minims and grains. The British National Formulary was born in 1948, did a good job for about 20 years, but sickened and died in 1976. It was reborn in 1981. Parturition was painful with a very hostile reception from the media and the drug industry, but it survived and has grown in stature. The 25th edition was published in February. Wish it well for the next 25 issues! PMID- 8490506 TI - Chronic liver disease due to hepatitis C. AB - The low concentration of hepatitis C virus in the blood of infected patients has made it difficult to detect. Infected patients can now be identified by using more sensitive immunoassays and amplification of viral RNA by the polymerase chain reaction. Nevertheless, the virus remains difficult to eliminate. We present the case of a woman with a history of autoimmune haemolytic anaemia, thrombocytopenia, and common variable immunodeficiency who developed chronic hepatitis. PMID- 8490507 TI - ABC of sleep disorders. The sleep apnoea/hypopnoea syndrome and snoring. PMID- 8490508 TI - Intraocular foreign body missed by radiography. PMID- 8490509 TI - Selective decontamination of the gut. PMID- 8490510 TI - Selective decontamination of the gut. PMID- 8490511 TI - Infertility linked to breast cancer. PMID- 8490512 TI - Prenatal diagnosis of late onset diseases. PMID- 8490513 TI - Clinical diagnosis of pyloric stenosis. PMID- 8490514 TI - Dose equivalence of drugs for asthma. PMID- 8490515 TI - Dose equivalence of drugs for asthma. PMID- 8490516 TI - Toxic shock syndrome after minor dermatological surgery. PMID- 8490517 TI - Night visiting in general practice. PMID- 8490518 TI - Methodology in health services research. PMID- 8490519 TI - Rate of asthmatic attacks. PMID- 8490520 TI - Communication between GPs and psychiatrists. PMID- 8490521 TI - Communication between GPs and psychiatrists. PMID- 8490522 TI - Search for primary cancer. PMID- 8490523 TI - Gulf war casualties revised. PMID- 8490524 TI - Interventional genetics and cancer treatment. PMID- 8490525 TI - Traumatic rupture of the diaphragm. PMID- 8490526 TI - Protecting the population in occupied areas of Croatia. PMID- 8490527 TI - Cost effectiveness league tables. PMID- 8490528 TI - National Blood Authority. PMID- 8490529 TI - Rational care needed, not rationing. PMID- 8490530 TI - The development of a physiological hip prosthesis: evaluation of the strains after implantation of a prototype of hip implant: experiment in a dry femur. AB - Based upon previous research on the relation between hip prosthesis designs and strain distributions in a proximal femur model, a prototype of a "physiological" hip prosthesis was designed and manufactured. Strain gauge measurements on a dry femur before and after implantation of this prosthesis were made in different loading conditions simulating one-legged stance with and without torsional loading and two-legged stance. The strains in the outer cortex were within 10% of the physiological values along the whole medial side in all measurement conditions. PMID- 8490531 TI - Energy absorption characteristics of football helmets under low and high rates of loading. AB - The purpose of this study was to examine the force-deformation characteristics of football helmets subjected to compressive loading on the crown surface. Tests were conducted at quasi-static and dynamic rates of loading. Energies were computed from the force-deformation data. The padding systems represented by the helmets differed in their ability to absorb energy under varying loading rates. Helmets using pneumatic or combination pneumatic-foam padding systems were the most successful while suspension helmets were able to absorb the least amount of energy. The evaluation of energy absorption characteristics is an alternative method of describing the effectiveness of football helmets in preventing head injury. PMID- 8490532 TI - Effect of exercise on strength and chemical composition of rat femur bone. AB - The effect of exercise on strength and chemical composition of rat femur bone was examined. Ten 5-week-old rats were forced to exercise on a treadmill with a running speed of 20 m/min at set time intervals for a 4-week period. Another 10 rats were kept idle as controls. After exercising, bending tests of the rat femur bones were carried out, and the content ratios of Sr to Ca, Sr/Ca, were measured by energy-dispersive fluorescent X-ray analysis and EPMA line analysis. The strength of the exercise group was greater than that of the control group. The ratio, Sr/Ca, of the exercise group showed a tendency to increase compared to that of the control group. It is clear that the chemical composition of bone varies with the degree of exercise, and that the bone becomes strengthened at the same time.